Pathology Flashcards

Question

what would we examine the brain for in a case of sudden death to prove it was the cause

Answer 1

History- Trauma, Seizures Gross examination- Skull fractures, Areas of haemorrhage in the brain Microscopic examination- Unless obvious trauma/haemorrhage, is difficult Hypoxic events and seizures will typically leave no trace visible by histopathology- Diagnosis of exclusion

Answer 2

damage to the autonomic nervous system and sudden death

Answer 3

catecholamines- tese hormones are released into the body in response to physical or emotional stress. The main types of catecholamines are dopamine, norepinephrine, and epinephrine. Epinephrine is also known as adrenaline.

Answer 4

Agonal changes take place immediately before death and are due to circulatory failure. The most common change of which to beware in this category is hypostatic congestion of the lower lung, which may be confused with pneu- monia.

Answer 5

cardiovascular

Answer 6

Structural Electrical Ischaemic

Answer 7

Ischaemic Shock

Answer 8

Pathophysiology of death due to cardiac failure-Structural Electrical- diagnosis of exclusion Ischaemic - a condition in which the blood flow (and thus oxygen) is restricted or reduced in a part of the body- may see hypoxia if animal lives for 6 hours after Pathophysiology of death due to vascular failure- Ischaemic- infarction, thrombus, Shock

Answer 9

Pathology of the vessels- Evidence of haemorrhage? Evidence of disease of organs involved in fluid and electrolyte haemostasis? -GI, Urinary, Endocrine (addisons disease?) Open pulmonary arteries and aortic bifurcation Take sections of kidney for histeopath - End arteries therefore good place to look for small thromboemboli

Answer 10

Pericardial effusion? Weight Measurements Gross lesions Sections for histopathology

Answer 11

"Respiratory failure occurs when there is inadequate exchange of O2 and CO2 to meet the needs of metabolism, which leads to hypoxaemia, with or without hypercarbia" Respiratory failure can be divided into: Type I respiratory failure, in which processes that impair oxygen transfer in the lung cause hypoxaemia (acute or hypoxaemic respiratory failure) Type II respiratory failure, in which inadequate ventilation leads to retention of CO2 , with hypercarbia and hypoxaemia ‘Mixed’ respiratory failure, in which there is a combination of type I and type II respiratory failure (acute-on-chronic respiratory failure). The most common cause of death due to respiratory failure in dogs is reported to be accidental asphyxiation due to choking on food material Acute respiratory distress syndrome- Secondary to inflammation/infections elsewhere in the body, Often pancreatitis, Sudden but likely expected and/or dog already hospitalised BOAS- Brachycephalic Obstructive Airway Syndrome Heat stroke Peri-anaesthetic

Answer 12

in which processes that impair oxygen transfer in the lung cause hypoxaemia (acute or hypoxaemic respiratory failure) low presure- high altitude hypoventilation under anasthesia ventilation diffusion imparment perfuion mismathc right to left shunt

Answer 13

in which inadequate ventilation leads to retention of CO2 , with hypercarbia and hypoxaemia abnomalities of cantral respiritory drive neuromuscular dysfunction abnormalities of chest wall abnormalities of airway abnormalities of lungs

Answer 14

in which there is a combination of type I and type II respiratory failure (acute-on-chronic respiratory failure).

Answer 15

"Brachycephalic obstructive airway syndrome (BOAS) is a term used to describe a raft of upper respiratory tract problems that occur in brachycephalic breeds. Clinical signs vary in severity and include stertor (noise), stridor ( increased effort), exercise intolerance, collapse and cyanosis (blue colouring). Affected dogs are also predisposed to syncope, gastro-oesophageal reflux, vomiting and regurgitation."

Answer 16

cause eof repiritory sudden death Pulmonary haemorrhage is a common clinical condition and PM finding in equine athletes. Exercise-associated fatal pulmonary haemorrhage (EAFPH)- describe fatal pulmonary haemorrhages in racehorses Fatal pulmonary haemorrhage is one of the most frequent causes of sudden death in racehorses, and such lethal pulmonary bleeding has been reported long before the acronym EAFPH was coined The occurrence of acute cardiac failure or spastic contraction of pulmonary postcapillary sphincters have been listed as possible pathogenetic mechanisms for the occurrence of EAFPH, but this has not been proven Exercise-induced pulmonary haemorrhage (EIPH)- The term was first used in1981 to describe epistaxis of pulmonary origin, especially after exercise. EIPH is believed to be an important cause of reduced athletic performance, especially in cases with severe bleeding, however its role in sudden death is complicated

Answer 17

A term first reported in 2015, used to describe fatal pulmonary haemorrhages in racehorses Fatal pulmonary haemorrhage is one of the most frequent causes of sudden death in racehorses, and such lethal pulmonary bleeding has been reported long before the acronym EAFPH was coined The occurrence of acute cardiac failure or spastic contraction of pulmonary postcapillary sphincters have been listed as possible pathogenetic mechanisms for the occurrence of EAFPH, but this has not been proven post mortem findings will show widespread blue/black discolouration on the lungs distinguishabke by its spread from the more schronic case seen in EIPH

Answer 18

The term was first used in1981 to describe epistaxis of pulmonary origin, especially after exercise. EIPH is believed to be an important cause of reduced athletic performance, especially in cases with severe bleeding, however its role in sudden death is complicated post mortem findings of the lungs in which this occurs may show blue black areas on the doral aspect of the lungs will have haemociderophages- macrophages that have taken up blood suggests chronic condition

Answer 19

Aetiology = Streptococcus equi subsp. Zooepidemicus

Answer 20

Aetiology = Streptococcus equi subsp. Zooepidemicus Pathogenesis is unclear however stress and concurrent viral infections may play a role Typical gross finding is that of a thoracic cavity filled with blood and histopathology of the lungs reveals a necrotizing suppurative bronchopneumonia: suprative- lots of neutrophils, necrotising- necrosis of the alveolar walls

Answer 21

Extraintestinal E. coli will also cause a haemorrhagic pneumonia

Answer 22

Extraintestinal E. coli Streptococcus equi subsp. Zooepidemicus

Answer 23

Several factors make the definition of ‘sudden death’ in farm animals problematic. The most commonly accepted definition is death that occurs since the last inspection (ie, within 12 to 24 hours). However, it can be challenging for the farmer to detect early clinical signs of disease in farm animals due to - Extensive husbandry Infrequent inspection Difficulty in recognition of individual animals difficult. Animals often scavenged Trauma- Dog attack Electrocution- Often asked to pronounce on suspected lightning strike due to its common inclusion in insurance policies. Circumstantial evidence, such as nearby trees, water or wire fencing, plus knowledge of a recent storm, is vital to diagnosis. Multiple animals dead by metal railings if due to faulty electrical equipment Death is usually instantaneous with few distinguishing features There may be singe marks on the skin, a rapid onset and disappearance of rigor mortis and rapid decomposition of the carcase with distension of the rumen. only consistant finding in electrocution cases is quick onset of rigor mortis in combination with it quickly fading Acute infection- Anthrax Clostridial diseases

Answer 24

Anthrax is a cause of outbreaks of sudden death, particularly in ruminants, however can affect other grazing animals and humans. Clinical signs in animals that do not die suddenly include high fever, tachycardia and tachypnoea, and congested and terminally cyanotic mucosae with haemorrhage. Animals that survive longer than a day may have dysentery, abortion, oedematous swellings of the perineum, throat and abdominal wall, and blood-stained milk. The characteristic sign in pigs is swelling of the pharyngeal region and neck. Anthrax is notifiable and zoonotic, so if you suspect it you must call APHA Triage all calls before accepting dead ruminants for PM Due to the high fever, animals decompose rapidly resulting in typical saw-horse bloated appearance DO NOT open up the animal, it is spread by spores which can become aerosolised If the animal has been accidentally opened up, immediate gross post mortem findings include blood filled cavities and marked splenomegaly- not many other things in cattle cause this often in sudden death the spleen contracts due to shock unless barbituates are involved Diagnosed in field by taking a blood smear from the ear Rod-shaped bacteria with capsule

Answer 25

Whist the GIT is not an organ that can kill you quickly, clostridial organisms found in the GIT can under the right circumstances produce toxins that affect predominantly affect the CVS and neurological systems Pathophysiology: Clostridium perfringens is a gram positive anaerobic bacillus C. perfringens types B and D produce epsilon toxin (ETX) resulting in enterotoxemia ETX is a pore forming toxin with particular affinity for vascular endothelial cells This changes the permeability of the small and large intestine The other target organs of the toxin include the kidneys, lungs and brain toxins cause disease Clostridium perfringens epsilon toxin: the third most potent bacterial toxin known C. perfringens is a commensal however certain situations can result in overgrowth Typically fat lambs or animals that have broken into feed containers or gone onto lush grazing Waning of maternal immunity Antibiotic use in rodents – C. difficile. watery bloody diherea fluid filled intestins toxins go to kidney lung and brain effect cardiovascular and neurological systems Gross pathology Fluid accumulation, mucosal haemorrhaging and haemorrhagic content in the small intestine and large intestine- may occur in pericardial sack Also seen in all species with clostridial enteritis Pigs may have emphysematous wall Widespread haemorrhages Hydropericardium, hydrothorax and pulmonary oedema “Pulpy” (soft) kidneys Brain General brain swelling leads to flattening of the gyri and cerebellar coning in some cases. cerebella coning- The herniation of the cerebellar tonsils through the forament magnum Symmetrical focal malacia (softening) - perhaps due to glutamate as this part of brain is heaily relinant on it and it is an exitable chemicale looks brown grey Diagnosis- Culture of intestinal content not useful as is a commensal Ileal content- Look for the toxin, often breaks down before it is found though ( it is "Labile") Glucosuria is typical but not pathognomonic as indicates systemic toxaemia Histopathology- Brain, white matter protein-rich perivascular oedema (microangiopathy)- this is due to the pore forming toxin

Answer 26

happens when pigs engorge with water- maybe sue to not having acces for a while show muscle fasciculation, blindness, seizures or were down, non-responsive. No significant gross pathological lesions are evident in the brain eosinophils may be seen

Answer 27

protien Produced in the liver at a constant rate Major contributor to plasma oncotic pressure Carries ion molecules (calcium, magnesium)

Answer 28

Oncotic pressure, or colloid osmotic-pressure, is a form of osmotic pressure induced by the proteins, notably albumin, in a blood vessel's plasma (blood/liquid) that causes a pull on fluid back into the capillary. protiens contribute to this

Answer 29

Subdivided into: Alpha, beta, and gamma globulins Includes: Inflammatory cytokines, immunoglobulins Produced by many different cell types. Major contributors: Liver: Acute phase proteins (increased during inflammation), coagulation proteins (clotting factors, anticoagulants) Lymphocytes: Immunoglobulins

Answer 30

dehydration

Answer 31

dehydration, inflammation, neoplasia Neoplasia refers to lymphoma & myeloma, which produce monoclonal immunoglobulins Detection of monoclonal immunoglobulins can be done via serum protein electrophoresis

Answer 32

Hypoproteinaemia can be categorised as follows: Selective hypoproteinaemia Hypoalbuminaemia Hypoglobulinaemia Total proteins can be WRI Panhypoproteinaemia Both albumin and globulins are below WRI

Answer 33

Hypoalbuminaemia Hypoglobulinaemia Total proteins can be WRI (reference interval) - total protien is normal albumin and globulins should be looked at seperatly

Answer 34

Both albumin and globulins are below WRI (reference interval When both albumin and globulin are lost together. Two main categories: Protein-losing enteropathy (common)- Lymphoma IBD Lymphangiectasia Parasitism Protein-losing dermatopathy (rare → severe burns)-

Answer 35

Can be caused by: Reduced production Liver disease Inflammation- negative acute phase protien so a drop in albumin is a normal response to inflamation Losses: Renal disease → protein-losing nephropathy (PLN)- kidneys shouldnt loose protien, damage to the glomerulus can cause this to happen. it tend to be albumin that is lossed first due to it being more passible Movement from blood into body cavitary effusion

Answer 36

Rare! Encompasses so many proteins, unusual to lose so much of one that it has a significant impact on total globulins. Check dehydration is not masking concurrent hypoalbuminaemia Consider double checking with a reference laboratory Main differential: Immunodeficiency resulting in severe reductions immunoglobulin production (e.g. Severe combined immunodeficiency)

Answer 37

Generally used to check for cellular injury. Commonly measured enzymes can be broadly categorised into those from: Liver Biliary tract Muscle Pancreas Some enzymes are produced by multiple tissues → need to look at panels to work out which tissue is affected. ast is prosuced byt the liver and the muscle There can be multiple different versions of one enzyme: “isoenzyme”

Answer 38

when there are multiple different versions of one enzyme

Answer 39

1-2 x upper end of reference interval Exceptions given to when the half life is very small for that species, and for specific enzymes such as GGT.

Answer 40

2-4 x upper end of reference interval Exceptions given to when the half life is very small for that species, and for specific enzymes such as GGT.

Answer 41

5+ x upper end of reference interval Exceptions given to when the half life is very small for that species, and for specific enzymes such as GGT.

Answer 42

(sorbitol dehydrogenase) not very stable GLDH better option produced in liver Generally only used in large animals

Answer 43

produced in Liver, muscle more sensitive marer for liver than muscle Not useful in large animals Cat ALT has much shorter half life compared to dogs → smaller elevations are more clinically significant

Answer 44

Liver marker More stable than SDH

Answer 45

equal markers for Liver, muscle long half life

Answer 46

Biliary (within the liver), bone, intestines, steroid- diffrent isoenzyme Steroid isoenzyme only in dogs- important for cushings growing animals produce more alp due to bone growth but this can also happen with bone cancer colicing horses have increse only specilised equipmetn can tell siffrence between isoenzymes Cat ALP has much shorter half life compared to dogs → smaller elevations are more clinically significant Canine steroid ALP isoenzyme is elevated with both drugs (corticosteroids, phenobarbital), chronic stress, and hyperadrenocorticism

Answer 47

very specifically Biliary Small increases significant- mild, moderate and mared scale less usefull here Colostrum is high in GGT → increases in calves Can be used to check for passive transfer Also elevated in foals but not due to colostrum in horses: Increase in GGT associated with chronic biliary stasis Good indicator of chronic liver disease Persistent increases above 400 IU/L associated with poorer prognosis good sensitivity, low specificity in horses

Answer 48

Bile acids Bilirubin Cholesterol Albumin Glucose Coagulation factors

Answer 49

Produced by hepatocytes and excreted into the bile Degradation occurs in the gut, then the transformed bile acids are reabsorbed Transported to hepatocytes via the hepatic portal vein Hepatocytes uptake the transformed bile acids for reprocessing

Answer 50

Tests the ability of the liver to re-uptake bile acids from the portal vein. Patient is sampled after being starved for 8 hrs so no more bile acids are released, then resampled after being fed. Increases are supportive of either: Reduced hepatocellular function (NB: does not necessarily indicate failure) Portosystemic shunt (blood bypasses liver) Cholestasis (don’t bother running this test if bilirubin is increased!) → bile acids are usually high before and after stimulation testing Only measure single BA assay in horses BA stimulation test not applicable for continual grazers Will increase with prolonged fasting Highly specific for liver disease Good prognostic indicator Normal <15mmol/l Persistent increase >50mmol/l = Poor prognosis

Answer 51

Two main types of bilirubin: Unconjugated bilirubin Made during breakdown of heme (from dead RBCs) Insoluble; transported bound to albumin Conjugated bilirubin → negligible levels in health Has been processed by the liver and conjugated with glucuronide Water soluble; majority is transported free Delta bilirubin = conjugated bilirubin that is bound to albumin (tiny amount) Analysers can give three different types of bilirubin measurement: Total bilirubin- Total bilirubin = direct bilirubin + indirect bilirubin Direct bilirubin → measured value- Total conjugated bilirubin Indirect bilirubin → calculated value (total bilirubin - direct bilirubin)- Total unconjugated bilirubin Most analysers give only total bilirubin

Answer 52

Pre-hepatic = excessive breakdown of heme or inhibition of bilirubin uptake by hepatocytes Haemolysis, fasting (horses, cattle) Unconjugated bilirubin increases, can eventually lead to both being increased Hepatic = reduced ability to conjugate bilirubin Toxic insult, Leptospirosis (dogs, cattle) Both conjugated and unconjugated fractions increased Post-hepatic Gallstones, mucocoele, pancreatitis (cats) Unconjugated bilirubin increases first, then both increase as the system “backs up”

Answer 53

excessive breakdown of heme or inhibition of bilirubin uptake by hepatocytes Haemolysis, fasting (horses, cattle)- cows and horses get a normal ncrease of this Unconjugated bilirubin increases, can eventually lead to both being increased

Answer 54

reduced ability to conjugate bilirubin- stays in liver cells Toxic insult, Leptospirosis (dogs, cattle) Both conjugated and unconjugated fractions increased

Answer 55

problem with flow of bile Gallstones, mucocoele, pancreatitis (cats) Unconjugated bilirubin increases first, then both increase as the system “backs up”

Answer 56

Produced in the liver but other sources include: Uptake from food via lymphatics- Usually triglycerides increase also Release from adipose tissue during negative energy balance- Usually triglycerides increase also Increases can be particularly high if animal is overweight Present within the bile in high concentrations

Answer 57

Cholestasis- Look for concurrent increases in bilirubin, GGT, ALP Starvation/anorexia- Usually triglycerides increase also Recent meal- Usually triglycerides increase also Nephrotic syndrome- hepatocytes stimulated to make more cholesterol. not common

Answer 58

Reduced intestinal absorption GI disease, hypoadrenocorticism

Answer 59

If the liver is end-stage, then these can drop due to reduced production/storage.

Answer 60

Diabetic ketoacidosis Starvation (puppies, working dogs) Insulinoma → pancreatic neoplasm which produces insulin Artefact → use fluoride oxalate tube

Answer 61

Liver synthesizes coagulation factors Liver failure → prolonged coagulation times

Answer 62

CK AST ALT

Answer 63

Muscle marker Short half life

Answer 64

Half life of CK much shorter than AST. Ratios of these enzymes can vary depending on time point. NB: Owner handling and recent exercise

Answer 65

Used to diagnose pancreatitis but can also go up when GFR is reduced. LIPASE IS ALSO EXCRETED BY THE KIDNEYS, so kidney damage can also effect this Measured by a multitude of methods: DGGR lipase- Not fully sensitive or specific, but good screening test Can increase in dogs with hyperadrenocorticism Drugs can increase DGGR lipase: corticosteroids, heparin Specific pancreatic lipase immunoreactivity (cPLI, fPLI)- More specific and sensitive than DGGR lipase SNAP pancreatic lipase immunoreactivity - Qualitative test for a quick “yes” or “no” As a general rule, positive = positive, negative = maybe

Answer 66

Used to diagnose pancreatitis but can also go up when GFR is reduced. Poorly sensitive in cats lipase is generally better

Answer 67

Usually used to diagnose EPI (exocrine pancreatic insuficiency) (whereby levels are decreased) Can go up with pancreatitis or with incomplete starvation nonspecific for pancreatitis

Answer 68

Glomerulus Renal tubules- Proximal tubule Loop of Henlé Distal convoluted tubule Collecting duct

Answer 69

Electrolytes filtered out. Proteins should remain in blood.- Small amount of protein present in canine urine Location of juxtaglomerular apparatus (RAAS)

Answer 70

Resorb most electrolytes Activate Vitamin D- calceum homeostasus

Answer 71

Absorption of H2O in the descending limb. Absorption of NaCl in the ascending limb. Creates the medullary concentration gradient required to concentrate urine in the collecting duct.

Answer 72

Small amounts of electrolytes resorbed in DCT Collecting duct reabsorbs H2O → concentrated urine

Answer 73

Speed at which fluid is filtered out of the blood into the Bowman’s capsule Controlled by: Hydrostatic pressure- The rate at which blood enters the glomerular capillaries The rate at which blood leaves the glomerular capillaries The rate at which filtered fluid moves through the renal tubules Oncotic pressure- Amount of albumin within the peripheral blood

Answer 74

Increased in-flow: High cardiac output High blood pressure → idiopathic, hyperthyroidism Decreased in-flow: Low cardiac output → heart failure, shock Water loss (decreased hydrostatic pressure) → dehydration less inflow means thing sflow through slower and filtration slows down Compensation occurs via dilation/constriction of efferent vessel Compensation limited Reduced flow through tubules: Injury to glomerulus Injury to tubules Urinary obstruction → urolithiasis Increased flow through tubules Excretion of osmoactive substances Glucose → diabetes Mannitol → therapy Diuretics Loss of medullary tonicity - Psychogenic polydipsia (drinking an exessive amount) or diabetes insipidus → loss of electrolytes = “medullary washout” Liver failure → loss of urea production

Answer 75

Urea Creatinine SDMA Others used in literature but not routinely in clinical practice: Clearance of inulin or iohexol Neutrophil gelatinase-associated lipocalin (NGAL) Retinol binding protein

Answer 76

Released by muscles at a constant rate Excreted entirely by kidneys - no reuptake Concentration in blood dependent on: Production- Higher with heavy muscle mass → greyhounds Lower with muscle wasting → young and elderly patients Rate of excretion (i.e. GFR)- main reason to look at creatinine kidneys are resiliat- Requires damage to 75% of nephrons for increase so not sensative

Answer 77

Produced by the liver during protein metabolism Excreted by the kidneys - small amount of reuptake Provides the concentration gradient for loop of Henle raw diet may increase abouve reference interval GI bleeding may cause it but must be severe and is usually not main reason Concentration dependent on: Production- Reduced with liver failure Increased with high protein diet Increased with GI bleeding —> Controversy Rate of excretion (i.e. GFR)- Requires damage to 75% of nephrons

Answer 78

not dependent on muscle mass like creatanine Released by all nucleated cells at a constant rate Excreted entirely by kidneys - no reuptake Concentration in blood dependent on: Rate of excretion (i.e. GFR) Requires damage to 25% of nephrons unlike urea NB: Greyhounds have naturally high SDMA

Answer 79

Clearance of inulin or iohexol- Used routinely in human medicine Neutrophil gelatinase-associated lipocalin (NGAL)- Released by injured renal tissues Measured as urinary NGAL:Creatinine ratio High sensitivity, specificity unclear (also released by neutrophils) Retinol binding protein (RBP)- Made by liver and freely filtered Measured as urinary RBP:Creatinine ratio

Answer 80

Increase in urea, creatinine, and/or SDMA Classification: Pre-renal → renal blood supply, increased urea production Renal → problem with the kidney itself Post-renal → obstruction of urine outflow

Answer 81

how good is renal blood supply, increased urea production diet?

Answer 82

problem with the kidney itself

Answer 83

obstruction of urine outflow

Answer 84

Require a loss of 75% of functioning nephrons before increases are detected. For every doubling above reference interval, GFR reduces by 50%.

Answer 85

Used to evaluate the degree of renal injury via staging Useful in guiding therapy Schemes available for both acute and chronic renal disease

Answer 86

Step 1: Signalment Age Breed Step 2: History Onset of PUPD or anuria Collapse? Known toxin ingestion Skin lesions (Alabama rot) Step 3: Biochemistry / CBC Severity of the azotaemia Multiple organs affected Anaemia mild to moderate azitaemia- chronic marked- acute other organs effected? liver effected could indicate toxin end stage disease can lead to non regenerative aneamia

Answer 87

build up of ureamic acids- bosy goes into acidosis Clinical syndrome: Lethargy/depression Mucosal ulceration → oral, gastric Vomiting/diarrhoea Respiratory signs → uraemic pneumonitis, metastatic calcification Hypertension → can lead to hypertrophic cardiomyopathy Hypokalaemic myopathy (cats) → plantigrade stance, cervical ventroflexion Hyperkalaemic bradycardia → acute kidney injury & urinary obstruction Anaemia → non-regenerative

Answer 88

Sodium- Drops Chloride- Usually as per sodium, but can increase independently depending on the cause of the injury E.g. Fanconi’s syndrome Potassium- AKI or urinary obstruction: Increases in all species → can be severe CKD: Dogs & horses: Increases Cats: Decreases → may need supplementation Calcium- Variable AKI: Increases CKD: Increases at first, then drops during end-stage failure Urinary obstruction: Drops - but we don’t know why! Phosphate- Increases, cant be excreted Magnesium- Increases, cnat be excreted

Answer 89

Aim is to conserve water by retaining sodium Creates a concentration gradient to reabsorb H2O Chloride generally moves with sodium → NaCl Potassium secreted in exchange for sodium

Answer 90

Most abundant electrolyte Important factor in maintaining tonicity/osmotic pressure Increases due to: Free water loss → diabetes insipidus Water deprivation Too much- Salt poisoning Hyperaldosteronism- aldosterone is th ehormone that encorages the swithcing of sodium and potassium n the renal tubules Decreases due to losses from: GI tract → diarrhoea, vomiting Kidneys → medullary washout, diabetes mellitus (increases gfr) , hypoadrenocorticism (less aldosterone) Cavitary effusions Perspiration → horses

Answer 91

Second most abundant electrolyte Increases and decreases are usually in association with sodium Instances where you lose more chloride that sodium: Vomiting Pyloric outflow obstruction → GDV, LDA, foreign body Instances where you lose more sodium than chloride: Proximal small intestinal diarrhoea → pancreatitis Renal tubular injury → Fanconi’s syndrome Hypoadrenocorticism- not enough ardosterone

Answer 92

If NaCl is lost or gained, then sodium and chloride should increase or decrease in equal proportions. In order to work out if chloride levels are in proportion with sodium, a corrected chloride can be calculated. Corrected chloride = (Na / [centre of Na reference interval]) * Cl If the corrected chloride is WRI, then chloride is proportionate to sodium

Answer 93

Important regulator of pH and cell electrochemical gradient- Used by cells to exchange for H+ when blood pH is altered Exchanged for Na+ to maintain electrochemical gradient- Higher amounts of K+ inside cells vs outside Decreases are due to: Alkalosis Decreased intake → anorexia (very common in horses) Perspiration → horses Increases are due to: Acidosis Reduced renal excretion → CKD, AKI, urinary obstruction, hypoadrenocorticism Artefact (common) → haemolysis, delayed serum separation

Answer 94

Blood pH is tightly regulated ~7.4 Drop in blood pH = acidosis → increased H+

Answer 95

Blood pH is tightly regulated ~7.4 Climb in blood pH = alkalosis → decreased H+

Answer 96

acids or bases building up in tissues/blood

Answer 97

affected by ability to exhale CO2

Answer 98

Occurs when acids start building up in the tissues/blood or when bases are lost Metabolic acidosis causes: If you lose Na in excess of Cl (i.e. loss of NaHCO3) H2CO3 + NaCl → NaHCO3 + HCl ( retention of hydrochloric acid) NaHCO3 is excreted in: Pancreatic/biliary secretions → reabsorbed in small intestines in health Kidneys → reabsorbed again within tubules in health HCl gets left behind if you have: SMALL INTESTINAL DIARRHOEA Specific types of RENAL TUBULAR INJURY (e.g. Fanconi’s Syndrome) HYPOADRENOCORTICISM (affects ion exchange in kidney) Metabolic acidosis causes: If you retain acids → measurable with Anion Gap Ketones → DIABETES MELLITUS Lactate → INJURED OR HYPOXIC TISSUES Uraemic acids → RENAL INJURY

Answer 99

Occurs when acid is lost Metabolic alkalosis causes: If you lose HCl- VOMITING → gastric secretions high in HCl TWISTED STOMACH (GDV) or DISPLACED ABOMASUM → HCl secreted into stomach but cannot enter small intestine to be resorbed → “lost” in the stomach Pyloric outflow obstruction (GASTRIC FOREIGN BODY) → as above GASTROINTESTINAL STASIS → as above

Answer 100

Occurs when CO2 is not exhaled sufficiently CO2 is an acid → decreased exchange → build up of CO2 → acidosis Respiratory acidosis causes: Respiratory tract obstruction Pulmonary fibrosis Pulmonary thromboembolism Pulmonary neoplasia Pneumonia Anything that reduces O2/CO2 exchange…

Answer 101

Occurs when CO2 is exhaled excessively Respiratory alkalosis causes: Tachypnoea CO2 is an acid → increased exhalation → alkalosis

Answer 102

Where you have more than one acid/base disorder occurring concurrently: Renal failure with vomiting: Renal failure = metabolic acidosis Vomiting = metabolic alkalosis Diabetic ketoacidosis and pancreatitis: Ketoacidosis = metabolic acidosis Pancreatitis = metabolic acidosis +/- metabolic alkalosis (if there is vomiting) Septic abdomen (lactic acidosis) and hyperventilation: Sepsis = metabolic acidosis Hyperventilation = respiratory alkalosis Vomiting causing aspiration pneumonia: Vomiting = metabolic alkalosis Pneumonia = respiratory acidosis

Answer 103

Acidosis = excess H+ H+ taken into tissue and exchanged for K+ → rise in blood K+

Answer 104

Alkalosis = H+ deficit H+ taken out tissue and exchanged for K+ → drop in blood K+

Answer 105

Balanced controlled by PTH and Vitamin D Vitamin D less important in horses Excreted by the kidneys and absorbed by the intestines UV light for vitamin D production not applicable in veterinary species Dietary intake and balance important, especially in horses

Answer 106

total calcium bound to albumin and uraemic acids Total can increase or decrease with fluctuations in these negatively charged molecules → especially albumin low albumin should cause low calcium- if not check unbounded calcium

Answer 107

unbound calcium Levels very tightly controlled by PTH, vitamin D and calcitonin

Answer 108

HARD IONS G Hyperparathyroidism → decreased excretion and increased bone resorption Addison’s disease → decreased excretion Renal disease → decreased excretion D-hypervitaminosis → psoriasis cream, rodenticide poisoning Idiopathic → most common cause in cats Osteolytic → osteosarcoma Neoplastic → PTHrp Spurious → artefact, analyser error Granulomatous disease → macrophages produce vitamin D

Answer 109

Nutritional- Insufficient dietary intake Excessive phosphorus intake Hypomagnesaemia Renal- Chronic: insufficient Vitamin D production Not relevant in horses Acute: reduced tubular reabsorption Urinary tract obstruction: unknown Pregnancy/lactation Pancreatic pathology- EPI: reduced vit D absorption Acute pancreatitis: unknown Drugs/toxins- Ethylene glycol Furosemide Tissue injury- Massive necrosis (e.g. in tumours) Rhabdomyolysis, polysaccharide storage myopathy Rumen overload: unknown

Answer 110

Decreased excretion- Renal injury (but not in horses!) Release from injured cells- Massive necrosis (e.g. in tumours) Rhabdomyolysis, polysaccharide storage myopathy Artefact with haemolysis or sample storage Excessive vitamin D

Answer 111

Increased excretion- Hyperparathyroidism Fanconi’s syndrome (dogs) Renal failure in horses Reduced intake Hypovitaminosis D

Answer 112

Only rarely measured in practice. Has bound and unbound fractions like calcium. Most important aberrations: Increases with renal disease (reduced excretion) Decreases due to dietary deficiencies (aka staggers)

Answer 113

Some analytes are very specific to that individual- Intra-individual variation is small but group variation is wide E.g. creatinine Analyser precision and accuracy may not be perfect All analysers should be precise around decision thresholds A small degree of inaccuracy allowed → varies between analyte Analysers should be checked regularly → QC very important! Not all assays are perfectly linear Once a threshold is reached, higher or lower measurements can become less accurate and precise Sample haemolysis/lipaemia/icterus can interfere with some assays Seasonal/diurnal variation- Reference intervals may vary depending on the season or time of day Can be very important when monitoring medication Variations with breed and age- Greyhounds have many breed-specific variations Some analytes change as patients age Use of generic intervals for exotic species- “Reptile” intervals for lizards and snakes “Avian” intervals for chickens and parrots

Answer 114

ACTH levels used to help diagnose PPID ACTH levels peak naturally in Autumn Different reference ranges required in Autumn

Answer 115

the ability of a test to detect sick patients the ability of a test to exclude a disease when you get a negative result

Answer 116

the ability of a test to exclude a disease when you get a negative result when you get a positive reusult you know that the disese is present

Answer 117

Some diseases use decision thresholds to rule in/out disease. Very common when diagnosing endocrine disease. Examples: Basal cortisol → hypoadrenocorticism Total T4 → hypothyroidism/hyperthyroidism ACTH → PPID in horses IGF-1 → acromegaly in cats Fructosamine → diabetes mellitus Can vary depending on severity of the illness being diagnose- Infectious disease assays usually very sensitive, but may be a trade off for low specificity Screening tests often less specific Confirmatory tests often highly specific ROC curve analysis most common method- Enables selection of cut-off with highest sensitivity and specificity

Answer 118

Is my analyser QC and calibration up to date? Do I know the grey zone for the analyte? Electrolytes have very small grey zone Hormones typically have ~20% variability in assay precision How reliable is my decision threshold? Check recent papers or textbooks for sensitivity and specificities Is the sample haemolysed/lipaemic/icteric?- Check reagent inserts to work out if that analyte is affected Has my sample been taken/handled properly?- Artefacts can occur if not stored properly, Serum should be separated/spun soon after collection, Gel in serum tubes can interfere with some tests e.g. progesterone Is this test fully sensitive/specific?- Especially important with positive/negative results Sensitivity and specificity highly important Consider further tests if: Result does not fit clinical picture E.g. FIV positive antibody test in a young indoor cat Sensitivity or specificity are not sufficient for a confident diagnosis E.g. Patient tests positive highly sensitive but poorly specific test Quantitative result required for confirmation or monitoring purposes E.g. SNAP cPLI/fPLI tests vs quantitative lipase measurement

Answer 119

Farm animal: mostly herd health and disease control reasons: can do a thorough search for all kinds of disease that is just not possible on live animals domestic animals: in cases of sudden, uneplained death. to confirm/refine a clinical diagnosis, to obtain samples for further tests (microbial culture, histopathology), to assess the effect of treatment(s), to collect evidence in forensic cases, or to prevent further illnesses and deaths within in-contact animals (for example, within litters of young puppies or kittens).

Answer 120

E.coli VTEC 0175 anthrax TB Camplyobateriosis Avian influenza salmonella cryptosporisiosis leptosporosis orf ovine chlamysiosis psittacosis q fever ring worm zoonotic diphtheria

Answer 121

The spleen is particularly susceptible to extreme congestion relating to barbiturate euthanasia Crystal deposition on the endocardium is another common barbiturate associated change.

Answer 122

rigor mortis, livor mortis, and algor mortis Algor Mortis- the cooling of the body after death Livor Mortis The purple-red discoloration of the soft tissues due to postmortem gravity-dependent pooling of blood is livor mortis. Livor mortis may be observed either externally in the skin and mucous membranes or internally in the abdominal or thoracic viscera, most notably the lung, and typically develops within 30 minutes to 2 hours after death in humans.22 Livor mortis must be distinguished from hemorrhage. In livor mortis, the pooling of blood is entirely within dilated vascular channels, whereas hemorrhage is the escape of blood from the blood vessels and into the connective tissues or internal or external spaces. Therefore, hemorrhage within the soft tissues will not blanch when subjected to digital pressure. Livor mortis, however, depending on its stage of development may blanch when subjected to digital pressure. Rigor Mortis Immediately after death, a series of biochemical reactions occurs within the skeletal and cardiac muscle fibers throughout the body. Specifically, adenosine triphosphate (ATP), the molecular source of energy for muscular contraction, continues to be consumed by the muscle cells, resulting in cross-bridge formation between myosin and actin fibers. However, the regeneration of new ATP ceases upon death. Because ATP is required for the decoupling of actin and myosin fibers and the resultant relaxation of the muscle, relaxation can no longer occur after the limited supply of ATP is exhausted. As a result, the muscle fibers remain in a state of permanent contraction, unable to relax because of the lack of additional ATP.

Answer 123

the cooling of the body after death

Answer 124

The purple-red discoloration of the soft tissues due to postmortem gravity-dependent pooling of blood is livor mortis. Livor mortis may be observed either externally in the skin and mucous membranes or internally in the abdominal or thoracic viscera, most notably the lung, and typically develops within 30 minutes to 2 hours after death in humans.22 Livor mortis must be distinguished from hemorrhage. In livor mortis, the pooling of blood is entirely within dilated vascular channels, whereas hemorrhage is the escape of blood from the blood vessels and into the connective tissues or internal or external spaces. Therefore, hemorrhage within the soft tissues will not blanch when subjected to digital pressure. Livor mortis, however, depending on its stage of development may blanch when subjected to digital pressure.

Answer 125

Immediately after death, a series of biochemical reactions occurs within the skeletal and cardiac muscle fibers throughout the body. Specifically, adenosine triphosphate (ATP), the molecular source of energy for muscular contraction, continues to be consumed by the muscle cells, resulting in cross-bridge formation between myosin and actin fibers. However, the regeneration of new ATP ceases upon death. Because ATP is required for the decoupling of actin and myosin fibers and the resultant relaxation of the muscle, relaxation can no longer occur after the limited supply of ATP is exhausted. As a result, the muscle fibers remain in a state of permanent contraction, unable to relax because of the lack of additional ATP.

Answer 126

Adequate facilities must be available either at the zoo or within a reasonable distance for the post-mortem examination of all species held at the zoo Animals that die at the zoo should be examined post-mortem in accordance with veterinary advice. Where appropriate, samples for diagnosis or health monitoring should be taken for laboratory examination Following post-mortem examinations conducted on the zoo premises, carcasses and organs should be disposed of swiftly and in accordance with the Animals By-Products- if possible carcasses of interesting or importan tspecies should be offered to a recognised scientidic institution (Enforcement) (England) Regulations 2011

Answer 127

psittacosis avian influenza campylobacteriosis salmonella toxoplasmosis west nile virus

Answer 128

Immersion fixation involves the use of fixative solutions. Formaldehyde (10% neutral buffered formalin) is by far the most popular fixative used in histology since it penetrates the tissue well and creates crosslinks without affecting the sample tissue's antigenicity. While it is relatively slow to fix, it is highly recommended for immunohistochemical techniques Glutaraldehyde fixes quickly and provides great cytoplasmic and nuclear detail, but it penetrates poorly and deforms the alpha helix structure in proteins. As such, it is good for electron microscopy but not so for immunohistochemical staining. Paraformaldehyde (PFA) is an effective fixative that reacts with primary amines found in the protein to form crosslinks (“methylene bridges”). PFA works great in stabilizing proteins and preserving morphology, but it fixes very slowly (more than 24 hours for smaller tissues and up to a few weeks for larger tissues) and may mask antigenic sites. Perfusion fixation can best be described as fixation through blood flow. The fixative is injected into the heart and spreads through the entire body. Since the tissue doesn’t die until it is fixed, you can get a sample with perfect morphology. Unfortunately, the subject dies during the process.

Answer 129

Formalin (a solution of formaldehyde in water) preserves proteins and cellular organelles in a stepwise process. It penetrates tissues quickly then binds to lysine, tyrosine, asparagine, tryptophan, histidine, arginine, cysteine, and glutamine in all of the proteins present in a specimen. It is the reaction between formalin and uncharged reactive amino groups that leads to the formation of cross-links.

Answer 130

Formalin fixation is not selective, so cross-linking of target proteins with unrelated proteins can reduce immunoreactivity with target-specific antibodies. In addition, cross-linking can lead to significant changes in the three-dimensional conformation of proteins which may also reduce immunoreactivity. Fortunately, antigen retrieval methods, such as heat-based or enzymatic procedures, can reverse the undesirable changes caused by fixation

Answer 131

Health screening – to prove animal is healthy (pre GA/mixing/transfer) To uncover subclinical disease- Many exotics v good at hiding clinical signs, Some species unable to do thorough clinical examination eg. Tortoise (unable to palpate) To make a diagnosis To confirm a diagnosis To guide further clinical investigation/next steps- Focussed testing important To help determine prognosis To help monitor progress/changes Because we can??!

Answer 132

Consider reference ranges very critically: Different populations- diffrent genders may greatly vary unlike domestic species Clinical context Management context Lifestage/signalment Care with extrapolation between species Consider panels offered and if appropriate for exotic species Often very non specific clinical signs - Prey species so mask clinical signs Often seeing advanced disease process in these animals due to masking signs- Rapid diagnostics often important Need to narrow down differential diagnoses

Answer 133

Warm reptiles Fasting?- Crop emptying/species variation Post meal effects- Hypoglycaemia risks when starving these animals Prepare in advance- Consider which parameters are priority Skin preparation Clipping/plucking?- minimally as possible Cleaning- reptiles grimy Care with spirit/alcohol- cools reptiles Suitable equipment gotten before animal is anethsitised- Needle/syringe Microhaematocrit tubes Small sample tubes 0.3ml tubes/1.1ml tubes

Answer 134

Venipuncture techniques Appropriate restraint- Manual/chemical do we wan t a pre-anesthetic sample Anaesthesia/Sedation/Conscious- Stress of GA vs handling Other procedures Safety of isoflurane vs stress Experience/confidence level of operator- ga better for lessed experience stress and GA Can impact on bloods (eg pH/electrolytes from GA/CK from conscious handling) Appropriate anticoagulant Heparinised syringes- reduces risk of loosing blood form already small sample. rabbits and rodents also hsve very rapid clotting times EDTA – effective in some species but some birds & reptiles this will lyse red blood cells Lithium Heparin – usually appropriate anticoagulant, appropriate size, reduces need to take more samples

Answer 135

Lipemia is a turbidity of the sample caused by accumulation of lipoprotein particles Changes can be pathological or physiological May affect analysis/parameters

Answer 136

lymps vessel or sinus has been sampled through and so tissue fluid is in sample

Answer 137

Blood smear – 1 drop required- Huge amount of information PCV – can use microhaemtocrit tubes (40-75ul tubes)- Total Solids from spun section, Assessment of buffy coat Critical care parameters – 0.1-0.5ml blood- Electrolytes, pH, Glucose etc Use lithium heparin and don’t spin- Can then use for haematology & biochemistry

Answer 138

Anticoagulants- Haemolysis  protein, electrolytes, cell counts, enzymes Fasting- Ferrets, other small mammals – see lower levels Post meal- Elevations in glucose, total protein, uric acid Restraint -Elevations in creatinine kinase, AST Anaesthesia- Changes in electrolytes, creatinine kinase, . Consider preanaesthetic blood sampling if apprpriate

Answer 139

Maximum of 10% of total blood volume may be sampled from a healthy individual. We need to know the blood volume per kg of body weight Only 5% should be sampled in sick/debilitated animals Must consider blood loss through haematoma formation Most patients are compromised

Answer 140

Blood volume calculated as 10% bodyweight- Eg. 10ml circulating blood in 100g bird Blood volume that can safely be taken in birds around 1% BW- Eg. 1ml sample collection in 100g bird, 3.5ml from 350g bird Examples: Canary – 0.2ml Cockatiel – 1ml African Grey Parrot – 5ml Harris Hawk – 10ml Mute Swan – 100ml Consider post sampling haemorrhage

Answer 141

Lower blood volume than equivalent sized mammal/bird Blood volume calculated as 4-8% bodyweight- Eg. 4-8ml circulating blood in 100g reptile Sample volume that can safely be taken around 10% of Blood volume This equates to approximately 0.5% bodyweight Eg. 0.5ml from 100g snake, 3.5ml from 700g lizard

Answer 142

Blood volume calculated as 6-8% bodyweight- Eg. 6-8ml circulating blood in a 100g mammal Blood volume that can safely be taken in mammals around 1-2% of BW Examples: Dwarf Rabbit – 5ml Standard Rabbit– 20ml Giant breed Rabbit – 36ml Ferret – Jill 5ml Hob 10ml Guinea Pig – 8ml Rat – 2-3ml Mouse – 0.2-0.3ml Hedgehog 2-6ml

Answer 143

Cranial Vena Cava- Blind technique Anaesthesia (or moribund animals) Landmarks- clavical use short needle to avoid heart, slightly longer with ferret Ferret, Guinea pig, Hedgehog Jugular Vein Conformation may limit- short neck in guinie pigs Stress Respiratory compromise- rabbits breathing compromised in this position- glottis disloged from soft pallet Cranial pressure can be increased by occluding the jugular Rabbits, Ferrets, Hedgehogs , Other rodents Cephalic- As per dogs/cats Conformation may limit Gentle restraint Small blood samples Rabbits, Ferrets, Guinea Pigs and other hystricomorphs, Hedgehogs , Other rodents Lateral Saphenous- Ideal in rabbits Often smaller blood samples Lateral hind leg – cranial to hock Prone to collapse Lateral & Dorsal Tail Veins Rats & Mice Vasodilation helpful- warm tail in waterbath, anethetic agent, tourocate Avoid in Gerbils (tail slip) Marginal Ear Vein Rabbits, some deer Small Volumes Vasodilation helpful- warm ear with hand Head shaking can->vein laceration- EMLA/Local anaesthetic

Answer 144

Basilic/Wing/Brachial/Ulnar Vein- ventral aspect of elbow Bend the needle- not much sorft tissue Very fragile vein prone to haemorrhage- Can bruise easily Good for: most bird spp. esp if under GA Less easy in: very small or wriggly patients Medial Tarsal Vein- not GA needed Good for: most bird spp. esp waterfowl, gulls, Less easy in: Raptors (talons), corvids(scaly legs), v small passerines (small) Right Jugular Vein- Not all birds have a left jugular or is v. small Jugular apterium- one of the bare spaces between the feathered areas on the body of a bird. More difficult for left handed people Good for: Small passerines/psittacines/ raptors/ corvidsNot in: Pigeons (have no jugular vein or apterium, cervical plexux instead), Waterfowl ( no jugular apterium), Gulls

Answer 145

Jugular vein- Regarded as gold standard- low risk of lymp dilution Dorsal branch runs in line with ear (auricular) scale Ventral branch runs below ear scale Both v superficial Handling key – can be very stubborn Pressure after sampling very important- Can hit carotid artery- Can get haematomas due to clotting defects common in reptiles Subcarapacial sinus- Blind technique- Good for larger samples Higher risk of lymphodilution c/f jugular Bend the needle Can use even in drawn in/small animals Dorsal tail vein- Dorsal midline Palpate spine Smaller volumes Higher risk of lymphodilution c/f jugular Brachial plexus- Useful in larger tortoises Leg drawn out Can feel tendon behind carpal joint

Answer 146

Ventral Tail Vein- Care if species which autotomizes- Avoid hemipenes- go a quarter of the way down the tail Midline (like a cow!) Hit spine and draw back Reasonable sample sizes Common in lizards Only in large snakes Care if species which autotomizes Midline (like a cow!) ¼-1/3 way down to avoid hemipenes Hit spine and draw back Reasonable sample sizes Cardiocentesis- Safer than it sounds Some clinicians prefer to sedate Locate using doppler Stabilise heart Enter from caudal direction Advance the needle into the ventricle Allow to fill with the cardiac output

Answer 147

Protein electrophoresis Albumin:Globulin ratio Acute phase proteins (Early stages of use in exotics)

Answer 148

Not very sensitive as doesn’t differentiate between different proteins Includes albumin and globulins ↑ Haemoconcentration, Inflammation, vitellogenesis, lipaemia ↓Malnutrition/absorption, parasitism, hepatopathy, nephropathy, enteropathy, skin losses, lymph dilution

Answer 149

Difficult to assay accurately in practice- Low levels compared to domestic patients, Pre-albumin can affect analysis of albumin Protein Electrophoresis most accurate way to assay proteins- interpretation needs to be species specific expert Avian/Reptilian ↑ Haemoconcentration, vitellogenesis, follicular stasis ↓Malnutrition/absorption, parasitism, hepatopathy, nephropathy, enteropathy, skin losses

Answer 150

Avian Alpha globulins (acute phase proteins) ↑ Acute inflammation, reproductively active female (vitellogenesis) ↓hepatic disease but rarely seen Beta globulins (acute phase proteins & immunoglobulins) ↑ Acute inflammation, Acute or chronic disease response eg Aspergillosis, psittacosis Gamma globulin (immunoglobulins) ↑ Chronic inflammation, Acute or chronic disease response eg Aspergillosis, psittacosis Mammals Rabbits with E cuniculi often have higher gamma globulins Decreased Albumin:Globulin Ratio

Answer 151

ALT Widely used as marker of hepatocellular injury in domestic patients Not released in liver damage in exotic species so of little use ALP No use in relation to cholestasis Purely a marker of bone damage and turnover, elevated in young animals & MBD

Answer 152

Elevated in liver and muscle damage Must assess alongside Creatine Kinase for muscle damage and GLDH for liver damage ↑Hepatocellular damage, tissue damage

Answer 153

Avian Can be elevated from difficult venipuncture of muscle damage/necrosis ↑tissue damage (can see large magnitude increases), IM injections, catabolic states Short half life (16 hours) if very high pay attention Reptilian Present in skeletal and heart muscle and less in kidneys ↑ with muscle damage and post traumatic venipuncture Mammalian In skeletal, smooth & cardiac muscle ↑ with any disease process associated with muscle

Answer 154

Very short half life specific to liver damage but not sensitive to it Avian Specific for hepatocellular damage but not very sensitive ↑Hepatocellular damage Reptilian Useful indicator of hepatocellular damage but limited evidence Mammalian Not widely used

Answer 155

Marker of cholestasis in domestic patients AND exotics Also present in renal tissue in exotics- Excreted into urine so can’t be picked up on blood biochemistry Avian Specific for hepatocellular damage but not very sensitive ↑Biliary Stasis (Similar to ALT in mammals)

Answer 156

Mammals Circadian rhythm In rabbits caecotrophy makes fasted sample collection challenging so hard to tell if elevated levels relevant Only useful if consistently raised Hepatic coccidiosis in rabbits Avian Reliable indicator of liver function Beware post prandial increases up to 4.5 x normal range Some species lack gall bladder ↓ common in birds with microhepatica, poor feathering, overgrown malformed beak ↑Hepatic insufficiency Reptiles May be useful – major bile acid varies across reptilian taxa Much reduced post prandial elevations c/f birds (max 1.7 x range)

Answer 157

Bilirubin Some birds produce this and see inconsistent elevations with liver disease Some birds cannot produce bilirubin as most don’t have biliverdin reductase Generally don’t see icterus in avian patients Biliverdin Biliverdin primary bile pigment/end product of haemoglobin in reptiles Reptiles lack biliverdin reductase enzyme to produce bilirubin from biliverdin No commercial assay- so detect with Biliverdinuria-green urin

Answer 158

Handheld vs laboratory assays Human glucometers tend to underestimate) vs Veterinary glucometers oversestimate Mammals Herbivores vs carnivores Rabbits – useful prognostic indicator ↑ Stress, pain, food intake, severity of disease, GI obstruction vs stasis Ferrets (Guinea Pigs)- ↓ Insulinomas, septicaemia, severe liver disease, starvation- sick ferrets should have glucose checked Reptiles Very variable with spp, nutrition, environment, season ↑ with stress, high temps, pancreatic neoplasia and rarely DM ↓ anorexia, malnutrition, severe hepatic dysfunction, sepsis

Answer 159

Produced during times of tissue hypoperfusion Serial monitoring rather than single value for porgnosis ↑ shock, low cardiac output, acute liver failure, sepsis, seizures Mammals Ranges not well defined – rabbits may have higher lactate values than other mammals Reptiles Is a marker of anaerobic metabolism, can be used to assess physiological stress Birds Capture myopathy

Answer 160

Is useful marker to detect renal insufficiency Not v sensitive s doesn’t elevate quickly Avian Main indicator of renal function ↑ Renal disease, postprandial, esp in carnivores, dehydration, egg production, gout ↓Malnutrition/absorption, liver disease Reptiles Also primary end product of protein metabolism Dependent on reptile’s natural environment Terrestrial reptiles are uricotelic, Aquatic usually ureotelic Mammals Not useful – mammals excrete the water soluble nitrogenous waste product urea

Answer 161

Mammals Main marker of renal function alongside creatinine ↑dehydration, renal dysfunction (NB once 50-75% nephrons affected) Rabbits Diurnal fluctuation (related to caecotroph ingestion) Peaks in late afternoon/evening Avian Limited value ↑ 4-5 x with dehydration, not sensitive for detecting renal insufficiency Reptiles Less useful parameter except for in tortoises ↑dehydration as urea can be resorbed across the bladder to reduce water losos

Answer 162

Levels low consistently in birds and reptiles Don’t change with renal insufficiency

Answer 163

Total Calcium Ionised (c. 45%) – metabolically active (can diffuse into cells) Bound to Albumin (c. 40%) Being transported – not metabolically active Associated with other ions eg Lactate and Phosphate 10-15% - biologically inert Essential to measure Ionised calcium Ca:P ratio important In egg laying females See huge elevation in Calcium to produce egg shell This is predominantly Bound and not metabolically active Mammals ↑ neoplasia, renal failure, impaired excretion, Ca-rich diets (rabbits/G pigs) Hypocalcaemia Again total Ca can be misleading if iCa low but total Ca normal

Answer 164

Anything that causes cell injury disrupts cellular homeostasis. Cells can be injured by myriad causes, both from intrinsic and extrinsic sources. Damage occurs to cells through one or a combination of of four basic mechanisms: Adenosine triphosphate (ATP) depletion Permeabilization of cell membranes Disruption of biochemical pathways, especially those of protein synthesis DNA damage

Answer 165

Adenosine triphosphate (ATP) depletion Permeabilization of cell membranes Disruption of biochemical pathways, especially those of protein synthesis DNA damage

Answer 166

Hypoxia/anoxia- oxygen essentail to make Specific toxins

Answer 167

Hypoxia/anoxia Reactive oxygen species (free radicals)

Answer 168

Hypoxia/anoxia Reactive oxygen species (free radicals)

Answer 169

Endogenous causes Reactive oxygen species (free radicals) Replication errors Exogenous causes Ultraviolet light X-rays and gamma rays Certain plant toxins Viruses

Answer 170

Due to Failure of ATP-dependent enzymes and pumps/channels Increased membrane permeability Acute cell swelling is also known as hydropic degeneration Particularly in the liver (hepatocytes) and kidney(renal tubular epithelial cells In other cell types such as the skin (keratinocytes), cell swelling from influx of water is called ballooning degeneration. Can be reversible if inciting factor/agent is gone Three key histopathological changes in acute early and reversible cell injury visible with light microscopy are: Cell swelling Cytoplasmic vacuolation Hypereosinophilia Organelle changes, membrane blebs and myelin figures are typically only seen using ultrastructural examination (transmission electron microscopy)

Answer 171

Physiology of lipid metabolism Lipid is delivered to the hepatocyte from dietary sources or body fat stores in the form of free fatty acids (FFAs). A small amount of FFAs are also synthesized in the hepatocyte itself from acetate. Some of the FFAs are utilized for the synthesis of cholesterol and phospholipids, and some may be oxidized to ketone bodies (1). Most of the intracellular FFAs are esterified to triglycerides (2). Once triglycerides are produced, they must be complexed to a lipid acceptor protein (or apoprotein) prior to export from the cell (3) as lipoproteins. This requires protein and energy Triglycerides may accumulate if the balance between the synthesis of triglycerides and their utilization or mobilization is deranged. When intracellular triglycerides accumulate, a fatty liver results. Hypoxia Protein synthesis- Aflatoxin, Carbon tetrachloride

Answer 172

Four possible outcomes Repair Adapt- chronic low grade injury Senescence- dna damage Death Dysplasia -> dna damage- neoplasia Unsurprisingly, mitochondria, which are the organelles most susceptible to injury, are thought to direct many of the processes of cellular adaptation, senescence, and programmed death. The point at which reversible cell injury becomes irreversible is debateable, but likely is dependent on calcium haemostasis within the cell

Answer 173

In the face of chronic sub-lethal injury (or stressor), cells can adapt involving the following mechanisms: Hypertrophy an increase in cell size by virtue of an increase in number and size of organelles Hyperplasia an increase in cell number that only those cells capable of mitosis can undergo Atrophy a decrease in cell size by virtue of a decrease in number and size of organelles Metaplasia a change from one differentiated cell type to another of the same germ layer (e.g., from ciliated epithelium to stratified squamous epithelium in the respiratory tract) Dysplasia abnormal differentiation with features of cellular atypia These are physiologically normal responses, however can result in their own pathologies.

Answer 174

an increase in cell size by virtue of an increase in number and size of organelles Cellular hypertrophy is the process by which postmitotic cells, such as cardiac or skeletal myocytes, can grow. Physiological response to increased workload and/or hypoxia. In the heart, in the short term this is compensatory resulting in increased capacity. In the long term, accompanying changes, can lead to decompensation of the affected organ. The classic example in veterinary medicine is hypertrophic cardiomyopathy (HCM) in cats. The complex pathophysiology of HCM is still unclear. Reversible if due to treatable disease hyperthyroidism Do not confuse hypertrophy with hyperplasia

Answer 175

an increase in cell number that only those cells capable of mitosis can undergo Physiological response to increased, often hormonal, stimulus Puberty and pregnancy Thyroid hyperplasia - Goitre Maternal iodine deficiency will result in hyperplasia (and hypertrophy) of thyroid follicular epithelial cells in ruminants Rarely see it as bad as the image to the right, so should always weight and store thyroid glands (fixed and frozen) in cases of perinatal/neonatal death in ruminants Non-neoplastic enlargement of a tissue. Hyperplasia is often the result of hormonal influences (e.g. benign prostatic hyperplasia, perianal gland hyperplasia), tissue injury (e.g. regenerative nodules in the liver, granulation tissue with fibroplasia) or antigenic stimulation (lymphoid hyperplasia). Aspiration of hyperplastic lesions: Higher than expected cellularity Cells may display some mild criteria of malignancy Mildly increased N:C ratio Darker blue cytoplasm More prominent nucleoli Finer chromatin than normal

Answer 176

a decrease in cell size by virtue of a decrease in number and size of organelles Physiological response to lack of use/innervation/stimulation Classic example is the small liver of the puppy with a portosystemic shunt

Answer 177

a change from one differentiated cell type to another of the same germ layer (e.g., from ciliated epithelium to stratified squamous epithelium in the respiratory tract) Typically from a specialised and/or fragile type (ciliated or simple cuboidal) to a less specialised, more protective type (eg: stratified squamous or goblet cell) Vitamin A deficiency in parrots results in squamous metaplasia of respiratory and upper GIT epithelium Poorly understood mechanism Results in hyperkeratosis of oral cavity, conjunctiva, nasal lacrimal duct, upper alimentary tract, and respiratory tract Ducts of glands can become blocked by keratin, often resulting in huge keratin granulomas and rhinoliths

Answer 178

abnormal differentiation with features of cellular atypia When applied to epithelium, dysplasia implies an increase in the number of poorly differentiated or immature cells Can be a precursor to neoplasia Microscopic features: Variation in size (anisocytosis) Variation in shape (poikilocytosis) Hyperchromatic nuclei Large nuclei (karyomegaly) Increased size or number of nucleoli Mitotic figures Making the call between dysplasia and neoplasia is thus difficult A continuum Classic example is actinic keratosis on the pinna of white cats due to UV light A carcinoma will breach the basement membrane Dysplasia = disordered growth Common in epithelial tissue secondary to inflammation or irritation. Loss of uniformity of the individual cells Disordered architectural arrangement of the cells. Atypical cytologic features: Nuclear to cytoplasmic asynchrony Increased cytoplasmic basophilia Anisokaryosis and anisocytosis. Dysplasia can be cytologically difficult to distinguish from neoplasia as dysplastic lesions often contain more criteria of malignancy than strictly hyperplastic lesions.

Answer 179

cell with rapid turnover cells that continuously multiply and divide throughout life. This continual division of labile cells allows them to reproduce new stem cells and replace functional cells that are lost in the body.

Answer 180

a cellular state in which a cell remains out of the cell cycle but retains the capacity to divide. The unique ability of adult stem cells to maintain quiescence is crucial for life-long tissue homeostasis and regenerative capacity liver ect

Answer 181

neurons in the course of acquiring specialized functions, has irreversibly lost its ability to proliferate

Answer 182

an undifferentiated cell of a multicellular organism which is capable of giving rise to indefinitely more cells of the same type, and from which certain other kinds of cell arise by differentiation

Answer 183

Senescent cells are somatic cells that stop dividing- previously laibile or quessent cells can become senescent Senescent cells remain metabolically active Signals that induce senescence are typically due to DNA damage and/or tumour suppressor genes mediated by p53-21 or p16 p53 tells damaged cells to stop causes: geonimoc instability telomere attrition- aging causes these to get shorter epigenetic alteration loss of proteostasis deregulated nutrient sensing mitochondrial dysfunction cellular senesence stem cel exhastion altered intracelleular communication

Answer 184

Long-lived post mitotic cells (terminally diferentiated)- Neurones and muscle- will see Lipofuscin Senescent cells- Heterochromatin (dense and innactive, non replicating chromatin) accumulations seen by Transmission electron microscopy Not clinically relevant Biochemical markers of senescence- Lack proliferation markers Senescence-associated secretory phenotype (SASP) Research orientated

Answer 185

Wear-and-tear pigment Normal accumulation over time of lipoprotein in secondary lysosomes May accumulate excessively in certain circumstances- Phalaris poisoning in ruminants- the pigment wouth be seen in cytoplasm of neurons Intracellular, golden-brown, globular Ceroid- Very similar to lipofuscin but only accumulates in disease states- rare to see Brown gut in dogs with vitamin E deficiency Intracellular and extracellular

Answer 186

Very similar to lipofuscin but only accumulates in disease states- rare to see Brown gut in dogs with vitamin E deficiency Intracellular and extracellular

Answer 187

membrane-bound cell organelle that contains digestive enzymes. Lysosomes are involved with various cell processes. They break down excess or worn-out cell parts. They may be used to destroy invading viruses and bacteria. Intracellular Membrane-bound vesicles Contain enzymes Genetic disorders- lysosomal storage disorders- effects the brain- quite rare

Answer 188

exgenous- carbon, tattoo ink-can be seen in post mortem of lympnodes- vaccine adjuvant carotenoids, tetracyclins- endogenous- heamatogenous, non-heamatogenous

Answer 189

Lipofuscin and ceroid Melanin- Incidental colouration: Leptomeninges, Pig lungs - melanosis- distingushed form melanoma by flat symetrical appearence Hyperpigmentation- Endocrine skin disease (unclear why) Melanoma Hypopigmentation- Vitiligo- immune sytstem attacks melanin, Melanin incontinence: Some skin diseases of dermo-epidermal junction- could be indication od disease in dermis(pemphigus)

Answer 190

from Blood- Haemoglobin Haemosiderin- brown pigment form broken down blood in macrophages- heamociderophages- stain blue. happens with heamorage. can indicate heart failure when found in the lungs Haematoidi Porphyria- Heme synthesis disorder Deposition of porphyrin pigments in tissues can turn bone pinker and makes them florese cattle teeth may turn brown pink Parastitic haematin- Liver fluke eat blood and pass it out as parasitic haemotin- seen in liver Methaemoglobinaemina- Heme iron is oxidized from the ferrous (2+ ) to the ferric (3+ ) form Methaemoglobin is constantly being formed, but it is reduced to haemoglobin by the methaemoglobin reductase pathway Marked oxidant exposure may promote the formation of methaemoglobin. Oxidative agents include gallotannin metabolites- Red Maple/Acer can induce this in horses Associated with Heinz bodies (see haematology lectures next week) May also see haemolytic crisis The blood and mucous membranes may appear brown when >10% of the total hemoglobin has been converted to methemoglobin Rare genetic disease in humans causes brown pigmant in skin Carbon monoxide CO bind haemoglobin, forming carboxyhaemoglobin Much stronger binding than oxygen and slow to revert Cherry red mucous membranes, muscle and brain Bile and breakdown products- juandice

Answer 191

Haemoglobin imbibition- freeze thaw artifact, animal may have had masave haemorage then not pm-ed for a number of days Psuedomelanosis blue green streaking of tissue and facea Action of hydrogen sulphide (bacteria) on haemoglobin changes into FeS (ferris sulphide)

Answer 192

Carotenoids are found in leafy vegetables and in horses and Jersey cattle impart a yellow colour to adipose tissue and lipid-laden organs. dont confuse with yellow fat disease

Answer 193

Pathological calcification = deposition of calcium salts in soft tissues - typically as phosphates and carbonates Metastatic calcifi cation is due to increased circulating calcium levels Dystrophic calcification is secondary to necrosis

Answer 194

Cells are lysed, and the necrotic tissue is converted to a fluid phase Caused by: Bacteria Fungi- cryptococcus neoformans in the brain Most common in the CNS- cant really get any other type of necrosis Due to hypoxia Large amount of cells and cell membranes with little connective tissue so nithing really holds it in Gross- Soft, viscous focus, often with cavity containing creamy-yellow material (pus). Histo: Cell debris, eosinophilic fluid Very messy- hard to tell what struture is being observed

Answer 195

Tissue architecture/basic outline of necrotic cells is preserved. Suggestive of: hypoxic injury bacterial toxins chemical toxins Gross- Often well demarcated Especially if due to infarction Rim of inflammation Histo- Overall tissue architecture preserved, often with retention of basement membranes Necrotic cells display typical histologic evidence of necrosis Inflammation Early attempts at healing- Especially in kidney if basement membrane intact

Answer 196

Cheese-like A chronic coagulation necrosis- Typically due to body’s inability to remove the agent - intracellular bacteria Common in birds and reptiles - Reduced amounts of myeloperoxidase in heterophils (neutrophils). Gross: Friable, granular, white appearance Typically encapsulated Abscess/granuloma/pyogranuloma Histo: Loss of architecture- mush of calcified tissue Central accumulation of remnants of lysed leukocytes May have border of granulomatous inflammation and outer fibrous tissue (‘granuloma’) Often dystrophic calcification centrally. A classic bacterial example is Corynebacterium pseudotuberculosis

Answer 197

wet/moist, gaesious, dry

Answer 198

Three types Wet/moist: Area of necrotic tissue further degraded by liquefactive action of saprophytic bacteria. Death of animal may occur due to toxaemia/ sloughing of tissue Gross: soft, moist, red-brown to black. +/- gas, putrid odor (hydrogen sulfide). Gaseous: Bacteria proliferate and produce toxins in necrotic tissue. Usually anaerobic bacteria eg. Clostridium perfringens/ septicum. Bacteria introduced by penetrating wounds, necrotic tissue becomes anaerobic, bacterial growth and toxin production. Gross : dark red-black, gas bubbles, fluid and haemorrhagic exudate. Dry: Coagulation necrosis secondary to infarction followed by mummification (dehydration). Usually lower portion of extremity (tail, ears, udder). Ingested toxins- ergot, fescue, and frostbite. Peripheral arteriolar constriction and damage to capillaries. Thrombosis and infarction (also direct freezing injury and ice crystal formation in frostbite). Necrotic tissues depleted of water eg. by low humidity, resulting in mummification. NO bacteria proliferation. Gross: dry, shrivelled, brown-black. May slough.

Answer 199

Area of necrotic tissue further degraded by liquefactive action of saprophytic bacteria. Death of animal may occur due to toxaemia/ sloughing of tissue Gross: soft, moist, red-brown to black. +/- gas, putrid odor (hydrogen sulfide).

Answer 200

Bacteria proliferate and produce toxins in necrotic tissue. Usually anaerobic bacteria eg. Clostridium perfringens/ septicum. Bacteria introduced by penetrating wounds, necrotic tissue becomes anaerobic, bacterial growth and toxin production. Gross : dark red-black, gas bubbles, fluid and haemorrhagic exudate. can occur post death

Answer 201

Coagulation necrosis secondary to infarction followed by mummification (dehydration)- trapped animals in dry enviroments may display this Usually lower portion of extremity (tail, ears, udder). Ingested toxins- ergot, fescue, frostbite- Peripheral arteriolar constriction and damage to capillaries. Thrombosis and infarction (also direct freezing injury and ice crystal formation in frostbite). Necrotic tissues depleted of water eg. by low humidity, resulting in mummification. NO bacteria proliferation. Gross: dry, shrivelled, brown-black. May slough.

Answer 202

Nutritional, enzymatic, traumatic, and idiopathic. Focal areas of fat destruction. Nutritional fat necrosis Also known as steatitis or yellow fat disease Diet high in unsaturated fatty acids and low in vitamin E or other antioxidants ROS production and lipid peroxidation. Enzymatic necrosis of fat Pancreatitis Release of activated pancreatic lipases which liquefy adipocytes Fatty acids combine with calcium to form chalky white areas (saponification) Faint outlines of cells with basophilic calcium deposits and inflammation Traumatic necrosis of fat Crushing Idiopathic fat necrosis Necrosis of abdominal fat of Jersey/ Guernsey breeds Large masses of necrotic fat in mesentery, omentum and retroperitoneum. May cause intestinal stricture/stenosis. Gross: Firm, white, chalky. Histo: Necrotic fat not lost in processing. Eosinophilic to basophilic (if FFA’s react with Ca2+ to form soap) necrotic adipocytes.

Answer 203

Also known as steatitis or yellow fat disease- dont confuse with normal yellowing in horses Diet high in unsaturated fatty acids and low in vitamin E or other antioxidants- ROS production and lipid peroxidation.

Answer 204

Pancreatitis Release of activated pancreatic lipases which liquefy adipocytes Fatty acids combine with calcium to form chalky white areas (saponification) Faint outlines of cells with basophilic calcium deposits and inflammation hiseologically will show as spaces for fat surrounded by inflamation and heamorage. soponificaition will leave blue material

Answer 205

Necrosis of abdominal fat of Jersey/ Guernsey breeds- Large masses of necrotic fat in mesentery, omentum and retroperitoneum. May cause intestinal stricture/stenosis. Gross: Firm, white, chalky. Histo: Necrotic fat not lost in processing. Eosinophilic to basophilic (if FFA’s react with Ca2+ to form soap) necrotic adipocytes.

Answer 206

Blood vessel wall necrosis- associated with inflammation = vasculitis Antigen and antibody complexes deposition in arterial walls and fibrin leakage. Histo: Bright pink, amorphous hyaline (glassy) Thrombosis- inflamation hypertoropic epithelil cells in lumen

Answer 207

Definition - The formation of the cellular components of blood Location - In the mature animal this occurs primarily in the bone marrow Maturation, activation and some proliferation of lymphoid cells occurs in thymus, spleen and LNs Liver and spleen can also be recruited to produce blood cells – “extramedullary haematopoeisis”

Answer 208

the production of red blood cells. Tissue hypoxia detected in peritubular interstitial cells kidney These cells produce erythropoietin (EPO) EPO binds to BLU-E/CFU-E/rubriblasts stimulating signalling cascade Results in differentiation and survival of erythroid progenitors Leading to increased production of mature RBCs Other growth factors involved include IL-3, GM-CSF and Thrombopoeitin (TPO) Hormones that promote erythropoiesis in combination with EPO – thyroid hormone, androgens, glucocorticoid this means significant kidney disease can result in anemia- chronic renal disease

Answer 209

the production of leukocytes in blood, such as MONOCYTES and GRANULOCYTES. This process also produces precursor cells for MACROPHAGE and DENDRITIC CELLS found in the lymphoid tissue. Stimulated by factors such as IL-3, GM-CSF and G-CSF Act on CMPs/GMPs to differentiate into myeloblasts Production massively upregulated in response to inflammatory stimulus (eg macrophage inflammatory protein-2, IL-8, C5a Eosinophil differentiation – TH2 lymphocytes involved by producing Il-5 Basophil differentiation – IL-3 and others involved

Answer 210

the formation of platelets in the Bone marrow Stimulated by thrombopoietin (TPO) which is produced mainly in liver TPO stimulates megakaryocyte production and survival from megakaryoblasts Other factors involved include IL-3, GM-CSF, IL-11 and EPO animals anemic due to iron deficiency will have increased no. of platlets animals with liver disese still produce adiquate platlets

Answer 211

recognised by segmented nucleus granulocites Vital part of innate immune system “First responders” – hallmark of acute inflammation Methods of attack – phagocytosis, degranulation and extracellular traps (NETs)

Answer 212

recognised by pink granuals Involved in response to parasitic infection ?Involved in response to some viral infections- not clasically assositated with this though Major mediators of allergic responses

Answer 213

Play a role in reactions to parasites and allergic reactions Release histamine (along with mast cells)

Answer 214

mononuclear cells. thin rim of cytoplasm. smallest luekocyte Adaptive immune response T cells – cell mediated immunity B cells – humoral (antibody) production NK cells – innate immune system Many functions!

Answer 215

can be confused with neutrophils of leukocytes. bigger with more blue colouring an dmore cytoplasm Orchestrators of the immune response Phagocytosis and microbicidal Regulates immune response via cytokines Scavenger role Secretory Leave circulation to become tissue macrophages

Answer 216

Clinically significant thrombocytopenia Regenerative vs non-regenerative anemia Spherocytes Rouleux vs agglutination Hypochromia (iron deficiency)? Check machine leukocyte differentials Left shifts

Answer 217

Must be performed at x1000 (ie x100 oil lens) Count number of platelets in 10 x1000 fields of view Take average and multiply by 15-20 This gives an approximate count x10^9/L Don’t forget to correlate with clinical signs (eg petechiae) Remember clinically significant bleeding 2nd to thrombocytopenia unlikely unless count <50x10^9 Rule of thumb – if you can find platelets easily on the film patient unlikely to be bleeding from thrombocytopenia Try and perform the count in the monolayer – not too thin and not too thick

Answer 218

Key to answering this question is to assess for the degree of polychromasia Polychromatic red cells larger and bluer – retained RNA, released earlier from bone marrow- indicates regenerative anemia

Answer 219

Spherocytes are red blood cells that are sphere-shaped rather than the usual round doughnut shape. Spherocytes are more fragile than normal red cells and their presence is accompanied by anemias of varying severity. Dogs not cats Must look in right area of blood film – in monolayer where you can compare to red cells with central pallor Not in tail of film – everything will look like spherocytes!! Spherocytes appear smaller, perfectly round and more densely staining Their presence in significant numbers is suggestive of IMHA

Answer 220

Agglutination (“bunch of grapes”)- immune mediated anemia Rouleux (“stack of coins”)- high protien level

Answer 221

Iron deficiency Increased central pallour Pale staining Frequently fragile red cells (schistocytes, acanthocytes and keratocytes) Often associated thrombocytosis

Answer 222

an increase in the number of immature cell types among the blood cells in a sample of blood. Many (perhaps most) clinical mentions of left shift refer to the white blood cell lineage, particularly neutrophil-precursor band cells, thus signifying bandemia. Release of earlier granulocyte precursors from marrow Indication of increased neutrophil demand/consumption Inflammation/infection “Band” neutrophils

Answer 223

Neoplastic cells Toxic change? Infectious agents? Dysplastic change

Answer 224

Complete blood count (CBC) Blood film examination Ancillary tests

Answer 225

Haemoglobin (Hb) (uses a biochemical method) Red blood cell concentration (RBC/ul) Mean cell volume (MCV); average size of RBCs

Answer 226

calculated from those measured (HCT = MCV x RBC) Equivalent of manual PCV

Answer 227

calculated (MCH = Hb x10 / RBC)

Answer 228

MCHC=Hb/HCT

Answer 229

Red cell distribution width (RDW) – indication of variation in red cell size- bone marrow is trying to respond to an anema, larger cells are being released Reticulocyte counts/percentage – measure of regeneration, how many immature cells are being released from bone marrow Reticulocyte Hb – potential marker for iron deficiency Plateletcrit (PCT) – equivalent of HCT for platelets

Answer 230

PCV – percentage of red cells in a volume of blood. Manual technique. Centrifuged whole blood, red cells read as a % of column. Buffy coat assessment Plasma – clear/ straw or pink if haemolysed Total proteins measurement

Answer 231

Evaluating 3 main things: Red cell density – does it look anemic? Red cell regeneration – is the marrow trying to regenerate? Red cell morphology – are there any clues to the cause of an anemia? (Eg spherocytes, organisms etc) is the patient anaemic? Very subjective Will depend on how the blood film is made Use as a crude quality control measure – does the red cell density appear compatible with the HCT provided by our analyser?

Answer 232

Regenerative anemia – relatively short differential diagnosis list Non-regenerative - long differential diagnosis list

Answer 233

Anisocytosis Polychromatophils- when stained with diff quick type stain. Reticulocytes- stained with methalyn blue. same thing. these are immature red celss that still contain ribosomes mathalyn blue precipitates ribotsomes, making them reticulated. hence reticulocytes these immature red cells are seen in regenerative anemia as bone marrow is putting them out to regenerate the red blood cells Nucleated RBC- not cliniclaly significant in birds and reptiles. earlier stage of maturation of ed blood cells. shows bone marrow is trying to regenerate red blood cell count in the case of re generative anemia Howell-Jolly bodies- Are nuclear remnants. usually would be removed in bone marrow except in this case

Answer 234

On a Diff – Quik or Giemsa stained smear, young red cells containing reticulin show up as larger, bluer cells: polychromatophils Stain the same cells with New Methylene Blue, and you can see the reticulin : the cells are then called reticulocytes THEY ARE THE SAME CELLS

Answer 235

Most helpful/specific- Spherocytes Agglutination Eccentrocytes Heinz bodies Hypochromia Acanthocytes Schistocytes Less helpful/specific- Echinocytes (crenated cells) Keratocytes Ovalocytes Dacrocytes

Answer 236

sign of oxidative injury which can cause anemia. Haemoglobin is oxidised and pushed to cell margin, no longer functiona eccentrocytes - cresent moon shape heinz bodies- protruding heamoglobin, red nose shape Paracetamol in cats, onions, some toxins (eg Zinc), diabetic ketoacidosis are some common causes of Heinz bodies/eccentrocytes

Answer 237

red cells with spicules (small uneaven projections) form with alteration of lipid metabolsm which effects the cells membrane Lipid disorders Liver disease Fragmentation injury (eg haemangiosarcoma- neoplams of blood vessels involving liver and spleen)

Answer 238

Red cell fragments forming secondary to being squeezed through abnormal blood vessels (eg haemangiosarcoma) or being fragile (eg iron deficiency)

Answer 239

This usually occurs when there is not enough of the pigment that carries oxygen (hemoglobin) in the red blood cells.

Answer 240

the haemotropic Mycoplasmas in cats Babesia species in dogs Ehrlichia and Anaplasma in dogs FIV/FeLV

Answer 241

Leptospirosis Panleukopaenia, canine parvovirus equine infectious anaemia Feline coronavirus

Answer 242

To try and distinguish rouleux and true agglutination The sample is examined microscopically after the addition of saline. Rouleaux formations disperse, but agglutination persists.

Answer 243

Coomb’s reagent (containing antibodies to IgG, Igm and C3) in dilutions is reacted with washed patient red cells to detect those cells opsonised with antibody and complement Opsonised cells binding antibody agglutinate Agglutinated red cells fail to settle in round bottom wells Significantly positive result provides support for immune mediated component to anemia

Answer 244

Up to 50% blood volume may be lost into the GI tract before it is grossly visible in the faeces. These tests generally detect peroxidase activity (present in haemoglobin) and may be 50x more sensitive than visual examination. They are prone to false positives due to meat diets, vitamin C and some vegetables (eg brassicas, cantaloupe melon (true, it’s on Wikipedia!!)). It is advisable to feed restricted diets for at least 3d prior to the test. Which diets? Traditionally white meat has been used Rice / cottage cheese may be better Commercial dry diets. Variable but if heat treated may be OK. Can always send in sample of dry commercial food at same time as faeces.

Answer 245

so a higher proportion of O2, which is carried by the Hb, is available to be released to the tissues. Increased cardiac output: Serves to increase tissue oxygenation Increased RBC production: Tissue hypoxia causes the release of the hormone erythropoietin from the kidneys. Vasoconstriction: Shunting of blood away from tissues with low O2 demand (i.e. skin) to tissues with high O2 n demand (i.e. brain).

Answer 246

Mucous membrane pallor Lethargy Exercise intolerance Tachycardia Tachypnoea Collapse Icterus Melaena Pica

Answer 247

Based on MCV values Normocytic: erythrocytes of unremarkable size Microcytic (low MCV): iron deficiency Macrocytic (high MCV): Presence of immature RBCs (ie marrow trying to respond) some poodles, in some bone marrow disorders a common artefact in stored/old (usually posted) blood samples (RBCs swell up) Normochromic Hypochromic (low MCHC/MCH): in iron deficiency/ poor iron incorporation (with microcytosis) Presence of immature RBCs (are not fully haemoglobinised) Hyperchromic (high MCHC/MCH): Not physiologically possible Always artefact (i.e. haemolysis)

Answer 248

Regeneration is the body’s response to a fall in oxygenation The kidneys respond by releasing erythropoietin (EPO) This stimulates the bone marrow to increase red cell production Takes 3-5 days, and younger red cells (polychromatophils/ reticulocytes) increase in circulation Dogs and cats - expect reticulocyte response – horses retain retics in bone marrow, not seen in circulation; cattle/ sheep only with severe anaemia Regenerative anaemia Haemorrhage, haemolysis Non-regenerative anaemia Intra- and Extra-marrow diseases

Answer 249

Melaena (GI bleeding) Haematuria (Urinary tract) Epistaxis (nose bleeds) Post trauma/ surgery Marked ectoparasitism Some endoparasites (e.g. hookworm) With acute haemorrhage, 3 – 5 days needed for a marrow response – before this, appears non or poorly regenerative : ‘pre-regenerative’ lab results: Anaemia initially regenerative BUT prolonged external haemorrhage >>> iron deficiency >>> non-regenerative anaemia as iron supplies are exhausted Proteins will be normal in the acute stage, then decrease as fluid re-equilibrates

Answer 250

Cause not always obvious- Bleeding tumours Trauma Bleeding disorders Into tissue, cavities, lungs Surgery Respiratory” blood may be coughed, swallowed and appear as melaena No iron deficiency RBC breakdown products available for recycling Proteins normal or raised

Answer 251

a cause of regenerative anemia Extravascular- outside of blood vessels- More common Macrophages Spleen and liver ± Icterus (jaundice) Intravascular- Acute, severe Haemoglobinaemia Haemoglobinuria Ghost cells +/- icterus boith can occur at once- presentation is very accute

Answer 252

Immune-mediated (common – primary verses secondary) Infections (less common) Babesia Mycoplasma Inherited RBC metabolic defects (rare) Toxins Severe Hypophosphataemia (rare)

Answer 253

One of the most common causes of anaemia in dogs One of the most common immune-mediated Dz Primary IMHA (AIHA) Most common Idiopathic Breed predispositions Young-middle aged Female>male clinical signs- Lethargy, anorexia Pale mucous membranes +/- tachycardia, bounding pulses, systolic murmur ± Tachypnoea Jaundice Hepatosplenomegaly Pyrexia, mild lymphadenopathy Secondary IMHA Infections Neoplasia Drugs

Answer 254

common . Chronic inflammation Most common cause Usually mild/moderate Fe sequestration and inflammatory mediators shorten erythrocyte survival Endocrinopathies Hypothyroidism Hypoadrenocorticism Chronic renal failure Decreased erythropoietin production Decreased RBC lifespan with uraemic toxins At risk of GI haemorrhage

Answer 255

less common . Aplastic anaemia Damage to stem cells, microenvironment or both Non-regenerative anaemia, bicytopenia or pancytopenia Idiopathic Secondary to Toxins (i.e. bracken fern) Drugs (i.e. chemotherapy) Infections (i.e. Parvo) Immune mediated mechanisms 2. Pure red cell aplasia/PIMA Selective BM erythroid precursor damage Non-regenerative anaemia Immune mediated Secondary to FeLV 3. Myelophthisis Represents a space-occupying lesion in the BM that inhibits or displaces normal haematopoietic cells NEOPLASIA usually bone marrow derived but may originate elsewhere Lymphoma, Metastatic disease Non-regenerative anaemia, 4. Myelofibrosis Proliferation of BM with fibrous elements that inhibits or displaces normal haematopoietic cells Idiopathic Secondary to other BM diseases Often need BM biopsy for histopathology, not aspirate, to diagnose

Answer 256

having a high concentration of red blood cells in your blood. This makes the blood thicker and less able to travel through blood vessels and organs. Many of the symptoms of polycythaemia are caused by this sluggish flow of blood Increased red cell mass, evidenced in increased : Haemoglobin Packed cell volume (PCV) Haematocrit (HCT) Red blood cell count (RBC) Physiological- Breed related Reference intervals should be different for Greyhounds vs other dogs Thoroughbreds vs ponies Relative Dehydration (PCV up to 60%) fluid loss with a stable red cell mass Clinical signs may be present Lab test abnormalities increased serum total proteins Often but not always increased serum sodium increased urine specific gravity PRIMARY(absolute) Polycythaemia rubra vera Bone marrow neoplastic dz Clonal proliferation and maturation of RBCs WITHOUT normal feedback mechanisms EPO low (in theory!) neurological signs, seizures, paroxysmal sneezing, cardiopulmonary signs, retinal changes (high blood viscosity) High PCV!! (>65 SECONDARY(absolute) Hypoxia (altitude, heart/pulmonary dz) Bone Marrow responds>EPO>>RBC Solid tumours Renal carcinoma>> EPO>> >>RBC

Answer 257

Left shift Toxic change Reactive lymphocytes Atypical cells Infectious agents (NB – Analysers will not reliably pick out these things)

Answer 258

Acute phase proteins (Dogs CRP, Horses Fibrinogen and SAA) PCR and serology for infectious agents Bone marrow aspiration/biopsy PARR test (lymphoproliferative disease) Flow cytometry (classification of leukemias) Anti-neutrophil antibodies (uncommonly tested)

Answer 259

a higher neutrophil count in the blood than the normal reference range of absolute neutrophil count. 1. TO MEET DEMAND Infections Immune mediated diseases Inflammation Neoplasia (COMMON) 2. INDEPENDENT OF DEMAND Bone marrow neoplasia = Leukaemia (UNCOMMON) 3. Persistence in circulation Chronic stress Glucocorticoids (steroids) 4. Redistribution (shift from marginating to circulating pool) Excitement (epinephrine) Stress(glucocorticoids) increased blood pressure

Answer 260

Increased demand (migration into tissue) Bacterial sepsis, abscess Endotoxaemia, tumour necrosis Redistribution In response to acute endotoxaemia (shift from circulating to marginating pool) Decreased production Bone marrow dz, Drugs Increased destruction Immune mediated

Answer 261

Band neutrophils- released with increased demand Usually “U” shaped or “S” shaped nucleus with parallel sides ie minimal indentation/ segmentation Toxic neutrophils- Maturation defects Seen with increased demand Not necessarily sepsis, can happen with sterile demand Pyothorax, pancreatitis, pyometra etc. Dohle bodies Foamy cytoplasm Bluish cytoplasm Toxic granules - rare diagnosing toxicity is objective

Answer 262

1. Increased production in response to increased demand Persistent antigenic stimulation (fungal, protozoal, viral), Post vaccination, young animals 2. Increased production without demand Lymphoid Leukaemia, Lymphoma 3. Redistribution Excitement/acute stress (epinephrine response) (physiological; as for neutrophils) inhibition of recirculation, release from the thoracic duct Hypoadrenocorticism (10-20% of cases)

Answer 263

Loss of lymphocytes Loss of chylous fluid (rich in lymphocytes) Protein losing enteropathy, chylothorax Decreased production Viral infections, lympholytic drugs (for chemotherapy) Redistribution Chronic stress, Glucocorticoids (steroids) Trapped in lymph nodes move from circulation into bone marrow and tissues lymphocytolysis

Answer 264

1. Increased production by the bone marrow to meet demand Infections, immune-mediated dz, inflammation, necrosis, sepsis, neoplasia 2. Increased production by the bone marrow without demand Leukaemia (myelomonocytic) 3. Redistribution Chronic stress, Glucocorticoids (steroids) Move monocytes from the marginating to the circulating pool

Answer 265

1. Increased production in response to increased demand Parasitic infection, allergic disease”, inflammation of mast cell rich tissue (intestines, skin, lungs, uterus) 2. Increased production without demand Neoplasia (lymphoma, mast cell tumour, squamous cell carcinoma) Hypereosinophilic syndrome Peripheral eosinophilia & infiltration of organs with eosinophils without obvious cause Eosinophilic Leukaemia (rare) 3. Hypoadrenocorticism (lack of glucocorticoids)

Answer 266

1. Increased numbers due to increased demand Hypersensitivities drugs, food, insect bites/stings Parasitism especially Dirofiliaria, but also GI parasites, fleas and ticks Inflammation 2. Increased numbers without demand Paraneoplastic (particularly with mast cell tumours) Basophilic leukaemia (rare)

Answer 267

Leukocyte pattern due to the effect of increased cortisol Classically neutrophilia +/-monocytosis with lymphopenia and eosinopenia Most commonly seen dogs and cats May be absent when expected eg Addison’s disease

Answer 268

Endemic in UK Feline Haemotrophic Mycoplasmas collectively known as haemoplasmas Cause of Feline Infectious Anaemia - acute haemolytic anemia Transmission method not definitively established - suspected fleas or aggressive interactions higher prevalence in older male cats with out door access transmission in blood - all blood donors should be screened M. haemofelis (Mhf)- most pathogenic mild to severe clinical disease in healthy cats Candidatus M. haemomimutum (CMhm)- asymptomatic/milder disease most likely to be clinical in immune compromised patients /concurrent disease (e.g. FeLV, FIV) Candidatus M. turicensis (CMt) could cause small reduction in RBC indices, unlikely to develop clinical anemia - unless concurrent disease /immunocompromised Post infection -anaemia develops in 2-34 days Bacteremia and anaemia can last for weeks Cyclic/fluctuating numbers of bacteria Antibiotic therapy may control acute infection but won’t clear infection Recovered cats develop carrier status Low grade intermittent bacteremia with no anaemia or develop milder disease when stressed. Clinical Signs : M. haemofelis can cause variable, but often severe anemia Weakness, lethargy, pale mucous membranes Intermittent fever Tachycardia, tachypnea, haemic murmurs, depression, collapse Clinical Pathology Results: Regenerative anemia * Macrocytic and hypochromic anemia Increased reticulocytes (and may have nucleated red cells) +/- mild hyperbilirubinemia (haemolysis) Primarily extravascular haemolysis Coombs +ve and autoagglutination (production of Ab against erythrocytes) * Anemia may not be regenerative 1. Pre-regenerative anemia Bone marrow response takes 3-5 days to produce peak response 2. Immunocompromised patient/concurrent disease (e.g. FeLV) Impairs a normal bone marrow response PCR positive with non-regenerative, needs further investigation. diagnosis: Evaluation of fresh blood smear tiny rod, cocci or rings on the surface of erythrocytes In aged blood samples (e.g less day old), fall off erythrocytes low sensitivity test Need to distinguish between stain precipitate, Howell Jolly bodies, basophilic stippling Fastidious and non-culturable Gold standard is PCR detection in blood (detecting DNA from the bacteria) May get false negative if low numbers (decline in parasitemia, chronic carrier phase)

Answer 269

Emerging Tick borne disease Endemic in South and Central Europe Cases of infected non-travelled dogs, Babesia found in local tick population. Various tick sp. Dermacentor reticulatus, Riphicephalus) Restricted geography West Wales, South Devon, Essex. Different sp with varying pathogenicity, B. canis of concern in UK Can have co-infections with other TBD ( Ehrlichia, Borrelia, hepatozoon(imported dogs)) Tick infect blood with sporozoites during feeding Sporozoites invade RBC, differentiate into merozoites, divide by binary fission, rupture RBC, infect neighbouring RBC clinical signs- Variable clinical signs and presentations Mild to moderate disease and chronic carrier status can develop Complicated forms of disease Immunological syndromes Primary feature is haemolytic anaemia Haemolytic anemia, mild to severe (often severe with B. canis) Fever, lethargy, anorexia, jaundice, vomiting, haemoglobin Regenerative anemia Extravascular /intravascular destruction Intravascular destruction leads to haemoglobinuria and haemolysed plasma/serum Can be associated with development of autoantibodies (immune mediated component) Can have spherocytes and Coombs + result Often thrombocytopenia (and neutropenia) diagnoisis-Blood smear evaluation Low sensitivity method Intraerythrocytic Large paired piriform organisms Can be singular Other Babesia sp, can be ring shaped

Answer 270

Emerging disease (imported dogs) Rhipicephalus ticks (endemic Mediterranean basin) Unlikely to become endemic in UK, screen imported dogs. Ingestion of infected tick, sporozoites penetrate intestinal epithelium Disseminate to the haemolymphatic system, undergo replication Releasing merozoites that infect neutrophils. clinicla signs- Clinical signs related to the severity of parasitemia Low burdens may be asymptomatic/mild Higher parasite burdens - can have severe clinical signs Infected neutrophils have reduced bacteriocidal activity - risk of secondary infections Non-specific clinical signs - fever, lethargy, weight loss, chronic infections Hyperglobulinemia (from infections/chronic inflammation) Hypoalbuminemia (negative acute phase protein) Non-regenerative anaemia (anaemia of inflammatory disease) Neutrophilia diagnosis- Blood smear evaluation Elliptical to pale blue gamonts % of infection can vary, may be infected with no peripheral gamonts, especially in asymptomatic/mild cases Buffy coat smear (Similar as above but increases the number of neutrophils evaluated) PCR most sensitive method of detection

Answer 271

Present in Europe/Americas, screen imported dogs Mosquito vector Nemotode - Dirofilaria immitis, Dogs are definitive host (patent infections), cats are non-definitive hosts Three phases of life cycle: Microfilaria (blood) Larve (mosquito and tissue) Adult worm (pulmonary artery or in heavy burdens right atrium) clinicla signs in dogs- mild- aysymptomatoic or cought moderate- cough, exersise intolerance, abnomal lung sounds severe- cough, exersise intolerance, abnomal lung and heart sounds, enlarged liver, syncope, ascites, death caval syndrome- severe acute lethargy weaknesss, hemoglobinema, heamoglobinuria diagnosis/ detection- Features that affect detection Long life cycle - takes up to 7 months post infection before patent adults in PA Need to test after 7 month last possible exposure Only mature adults produce MF - occult infection of adults but no MF Need to know patient is Heartworm free before treating with microfilarial drugs (ivermectin / moxidectin) in case reaction to dying MF Animals infected with Heartworm require lengthy treatment protocol that will involve 6-8 weeks of STRICT cage restriction. Prevention is better than cure. Two types of screening tests 1. Detection of antigen Antigen (protein secreted by the mature adult female) Specificity good Sensitivity good and will detect most occult infections but…. Low adult female worm burdens may yield false negatives. Male only infections will yield false negatives Consider a negative result ‘not detected’ All positive results MUST to be confirmed prior to treatment- with a different antigen test, MF, cardiac ultrasound/radiographs etc. 2. Microfilarial test (modified Knott Test) 1ml EDTA blood: 9ml 2% formalin Mix and centrifuge Remove supernatant, put sediment on slide with coverslip Evaluate at low power under microscope Positive tests Validate positive antigen tests Indicate dog is a reservoir of infection Warning that high MF burden may react to microfilaricides American Heart worm society recommendations Dogs should be tested with BOTH antigen and Knotts test Positive antigen tests need confirmation before treatment Cats are not definitive hosts, greater resistance against Generally have low worm burdens - males >females (1-2 worms, often single sex) Seldom circulating microfilaria Clinical signs - generally associated with respiratory signs but can be asymptomatic Rarely severe dyspnoea, tachypnoea, collapse Testing is not reliable in cats Antigen testing (but a negative does not exclude infection) + Radiographs, echocardiography

Answer 272

Red Water fever / Piroplasmosis High prevalence in SW England Difference sp. but B. divergens and B.major (transmitted by Ixodes ricinus) occurs in UK. Small Babesia sp. Merozoites invade the erythrocytes, multiply, burst out destroying erythrocyte Cause of significant intravascular haemolytic anaemia Disease may be mild to severe, may be less severe in endemic regions if have immunity Severe clinical signs relate to the severity of haemolysis (can result in death) Fever, depression, icterus, anorexia, tachycardia, tachypnea, pale mucous membranes, haemoglobinuria Other signs could include reduced fertility/production/abortion. diagnosis- Clinical signs/pigmenturia/local knowledge/changes in pasture etc Fresh blood smear evaluation Single or paired round oval or pear shaped structures Low sensitivity PCR

Answer 273

A. Phagocytophilium - cause of Tick-borne fever Ixodes ricinus Obligate intracellular bacteria - unusual residence in neutrophils Causes disease via immunosuppression Reduced number of cells Reduced bacteriocidal function Affects lymphocyte signalling/function Infection on its own usually causes self limiting febrile disease Can also cause abortion, mild drop Increases susceptibility to other diseases (pasteurellosis, septicaemia) Causes persistent infection/carrier status - evades detection (changes surface proteins) Status can last up to 2 years Presence of bacteremia at various time points Peak bacteremia >50% granulocyte infected. diagnosis- Blood smear evaluation (but low sensitivity) Mulberry like micro-colonies (morulae) of coccobacciliary bacteria Size 0.2-05 um diameter Within cytoplasmic bound vacuoles PCR (pan-Piroplasmosis PCR for Babesia and Anaplasma, APHA) Serology (IFA, ELISA) (not routinely used )

Answer 274

Disease of concern Protozoa: Theileria equi (formerly Babesia equi) Babesia caballi Endemic in tropical and subtropical regions Tick borne disease - multiple tick vectors inc. Dermacentor reticularis Intra-erythrocytic disease Replicates in RBC, ruptures cells, merozoites released into the circulation, infects further RBC clinical signs- Both sp. induce similar disease, cannot be distinguished clinically Different forms of disease acute, sub-acute, chronic Acute Haemolytic anaemia (varying severity, can be severe) Icterus Haemoglobinuria (severe cases) Thrombocytopenia (destruction or consumption) Fever, inappetence, oedema (occasionally death) Chronic/carrier states Mild variable and non-specific signs Clinically indistinguishable from chronic inflammatory diseases Variable anaemia, lethargy, anorexia, weight loss, reduced performance and fertility, may be asymptomatic Still pose a reservoir for tick borne and iatrogenic transmission Not reportable or notifiable in UK No formal UK requirements for pre-import screening Asymptomatic horse could enter UK and seropositive horses are present in UK (2016 study reported 8% seropositivity of pre-export submissions!) Exposure to Dermacentor tick - could theoretically establish/transmit disease Iatrogenic transmission possible Can treat (imidiocarb) but T. Equi generally considered life long disease Serology tests (3 methods of antibody detection commercially available) cELISA- considered better test for detecting chronic infection CFT - more likely to detect acute infection IFT PCR - false negatives occur No test is perfect and a combination of serologic tests may be required (especially if suspicion of clinical disease). USA, Australia and Japan are disease free and require pre-import testing USDA recognises the cELISA as approved screening test

Answer 275

Candidatus Mycoplasma haemolamae Transmission unknown but suspected to be ticks? MANY infections are subclinical Above study; herd 131 llamas, 29% prevalence (PCR +ve) but no evidence on blood smear, healthy, non-anaemic population represents sub-clinical infection only one case developed clinical signs of anaemia (but had focus of inflammation) Mycoplasma haemolamae - potential cause of regenerative anaemia M. haemolamae secondary cause/associated with chronic disease GIT parasites (Haemonchus) most common cause of anaemia Higher GIT parasitemia more likely to be severe anaemia Haemonchus and M. Haemolamae together cause more severe anaemia diagnosis- RBC small and elliptoid Lots of small blue dots on surface of RBC Identify on blood smear (make fresh as organisms will fall off) PCR Positive result interpreted in context of clinical signs Is there anaemia? FEC, other disease

Answer 276

weakness and wasting of the body due to severe chronic illness

Answer 277

post mortem change green blue staining by FeS FeS is formed by H2S from putrefactive bacteria and iron from HB from lysed red blood cells will progress to black colouration under the right circumstances

Answer 278

it will increase the opacity

Answer 279

the red discolouration of tissue due to haem from lysed erythrocytes commonly seen as a freeze thaw artifact can also happen over time, esspecially in organs that contain a lot of blood like the heart

Answer 280

Occurred to the animal before it died Incidental findings True lesions

Answer 281

Occur at the time of death Lung and liver congestion

Answer 282

Occur as part of killing the animal Barbiturate crystals in heart Splenic congestion due to barbiturate euthanasia Gun shot damage to head Freeze-thaw/chilling artefact

Answer 283

Occurs after the animal is dead Rigor mortis Algor mortis Livor mortis/hypostatic congestion Pseudomelanosis Putrefaction Haemoglobin imbibition Autolysis

Answer 284

Focally raising the contour of the atrial surface of the mitral valve is a single, smooth red, round focus, measuring approximately 3mm in diameter Interpretation: blood cyst Seen frequently in young ruminants Incidental

Answer 285

Multifocally at the line of closure of the mitral valve the valve is thickened and pale cream with raised coalescent nodules. Age-related change commonly seen in older dogs must be interepreted in context How is this different to mitral valve disease?- vegitative lesions. not smooth.

Answer 286

incidental finding Difficult to see grossly but can sometimes in older dogs’ lungs, feel multifocal firm to gritty small areas within the parenchyma Age-related incidental calcification If widespread the main differential would be uraemic mineralisation/calcification due to renal failure of vitamin D poisoning

Answer 287

incidental finding Description: Multifocally within the meninges and over the surface of the dorsal cerebrum are multiple nematodes Interpretation: Paralaphestrongylus tenuis Non-pathogenic parasite of the white tailed deer (USA) Incidental in definitive host (white tail deer), causes neurologic disease in a number of aberrant ruminant hosts. Multifocally within the meninges and over the surface of the dorsal cerebrum are multiple nematodes Paralaphestrongylus tenuis Non-pathogenic parasite of the white tailed deer (USA), therefor typically incidental in these hosts Incidental in definitive host, causes neurologic disease in a number of aberrant ruminant, camelid and equine hosts.

Answer 288

incidental finding Description: Multifocally affecting all lobes of the liver are poorly-demarcated, flat, vaguely round, white to pale tan foci Interpretation: Ascarid migration Various species

Answer 289

possible incidental finding Description: Entirely obliterating the left lateral lobe of the lever is a large nodular vaguely round pink to red firm mass Interpretation/morphological diagnosis: Hepatocellular adenoma/carcinoma history important Only an issue if they rupture, can grow quite large in old dogs completely un-noticed However, a small proportion will produce insulin-like peptides or IGF-2 -> hypoglycaemia

Answer 290

posiible incidental finding Description: Focally expanding the parenchyma and raising the contour of the spleen is a focal, well-demarcated, black to red to pink mass Interpretation/morphological diagnosis: Nodular hyperplasia Can grow large, can rupture There are however lots of malignant neoplasms that can form masses in the spleen- Haemangiosarcoma Lymphoma Histiocytic sarcoma

Answer 291

possibel incidental finding Description: Focally extensively raising the capsule of the lateral aspect of the body of the spleen are raised cream to white to grey gritty multifocal to coalescing (squishing toghtther) plaques Interpretation: siderotic plaques Accumulations of debris associated with erythrocyte turnover. Histopathologically are quite pretty with multiple variations of metabolised haem- Haemosiderin Hemotoidin - Gamna-Gandy bodies

Answer 292

Renal cysts Can be incidental Can also be pathological Quantifying and contextualising is important can be common finding in slaughter pigs but alco couldy be pkd

Answer 293

Nucleated Larger than mammals’ smaller than reptiles’ Elliptical cells Elliptical, central nucleus Higher oxygen demand so higher than mammals Normal PCV 35-55% RBC Life span 28-35 days Lower red cell mass in juveniles Few significant gender influences 1-5% Polychromasia Higher % in juvenile birds Generally as a result of haemorrhage Toxicosis another common cause

Answer 294

Nucleated Larger cells than birds and mammals Blunt ended ellipse Central round/ovoid nucleus with Irregular margin Lower oxygen demand so lower PCV Normal PCV 20-40% RBC life span 600-800 days! Influence of gender, hibernation, environment – lots of variation May have mitotic figures in RBCs May see increased regeneration With blood loss or without blood loss

Answer 295

Anucleated (No nucleus) Anisocytosis/Polychromasia common in some species Shorter half life c/f dogs and cats Rodent and rabbit RBCs shorter half life c/f cats/dogs (45-68 days) PCV varies a little with species (Rabbits 30-50%) Can see high levels of regeneration Esp juveniles

Answer 296

Most common form of anaemia in reptiles Systemic disease Starvation Chronic disease GI disease Neoplasia Suboptimal Husbandry

Answer 297

Systemic disease Starvation Chronic disease Neoplasia Drugs Suboptimal Husbandry Many infectious diseases - spergillosis, Chlamydiosis, TB, circovirus, chronic bacterial infection

Answer 298

Granulocytes Lymphocytes Monoocytes Azuropohils (snakes)

Answer 299

Functionally the same Different staining Most mammals have neutrophils Rabbits and some rodents – heterophils Reptiles, Birds – heterophils Most common leukocyte to vary in disease Predominant leukocyte usually- Some species lymphocytic Rabbits, G. Pigs, mice, rats, gerbils Heterophil:lymphocyte ratio Function & Appearance of Heterophils/Neutrophils Phagocytosis and lysosomal action Irregularly round cell Granules Often rod shaped granules esp in birds Granules often fused together Basophilic nucleus Lobed - 2-3 lobes in birds Non lobed oval nucleus in reptiles Very variable appearance in reptiles

Answer 300

Stress (transport, restraint, fear, crowding, management, trauma, temperature stress, anaesthesia) Infectious causes , inflammation Neoplasia Necrosis Differentiate between physiological and pathological heterophilia Left shift (increased band heterophils) Less lobed nucleus More basophilic (bluer), fewer granules Toxic Changes (main marker in reptiles) NB reptiles huge variation Biochemistry changes (Fibrinogen assays, A:G ratios, acute phase proteins Pseudoheteropaenia True Hetero/Neutropaenia Sepsis Viral infections Myelosuppression Iatrogenic/drugs Neoplasia) Combined with left shift in severe consumption in overwhelming infection NB in Lymphocytic species, heterophil:ymphocyte ratio more reliable

Answer 301

Exact function unknown in some species Loosely foreign antigen Larger than heterophils with round outline Red/orange round cytoplasmic granules Some species have pale blue granules eg AGP/iguanas Birds – bilobed nucleus Reptiles – elongated/round nucleus Generally in fewer numbers Raptors higher eosinophils <15% Reptiles variable

Answer 302

Eosinopaenia Typically low numbers so eosinopaenia hard to identify/define Stress Glucocorticoids Eosinophilia Less clearly defined than in dogs/cats where usually parasites Artefactual Foreign Antigen Marked tissue trauma Parasites Rarely hypersensitivity

Answer 303

Slightly smaller than the monocyte Non segmented nucleus Darker more basophilic cytoplasm than monocyte Prominent red cytoplasmic granules Appearance and function more similar to neutrophils Can be <35% Increase with acute inflammation or bacterial infection (similar to neutrophils) but do also have heterophils No real clinical benefit in differentiating from monocytes

Answer 304

Nucleated cells Second most numerous cell in peripheral blood Small, round to oval cells Round to oval nucleus High Nucleus:Cytoplasm ratio May contain eosinophilic granules 1 or 2 in one area of the cytoplasm Clump or form aggregates in blood films Avian thrombocytes capable of phagocytosis Thrombocytopaenia Decreased BM production Excessive peripheral utilisation Chronic inflammatory conditions Severe septicaemia Thrombocytosis Chronic inflammation

Answer 305

Protozoan Haemoparasites Insect vectors (leeches in aquatic reptiles) Haemolytic anaemia Haemoproteus Plasmodium Leukocytozoon Trypanosomes Microfilaria of filarial nematodes

Answer 306

Rarely provide definitive diagnosis Significant variation with species, age, gender, lifestage Liver and Muscle AST & Bile Acids most sensitive indicators of liver disease AST not liver specific – can be elevated with muscle damage, inflammation, sepsis GLDH most specific marker oof hepatocellular damage Bile acids reliable indicator of liver function (must collect serum as heparin affects it) Post prandial bile acid elevation so fasted samples preferredCK elevation with muscle damage so should be used alongside AST and GLDH to differentiate ALT, ALP & GGT very non specific Bilirubin concentrations inconsistent in liver disease and across species Biliverdin primary bile pigment Renal Uric acid most reliable test of renal disease (NB affected by many factors) Dehydration and renal disease can both elevate uric acid Can be used as prognostic indicator for gout (>600uml can lead to precipitation in joints) Urea and creatinine not useful for renal disease Creatinine not synthesised by birds (Creatine instead) Urea can be useful for assessing hydration status (but 10-15 x increase not uncommon) Other Protein levels lower in birds c/f mammals Glucose levels more stable in birds as not utilised by RBCs but see stress and postprandial↑ BG ranges in birds higher than mamamls Calcium – consider total and ionised calcium Egg laying biochemistry

Answer 307

Lymph dilution common and will reduce all biochemical values Effects of sex, season profound Liver and muscle ALT, ALP, LDH non specific AST found in liver, kidneys & muscle so should be assessed alongside CK and LDH GGT in liver and kidneys; sensitive for hepatic & renal disease GDH may be useful indicator of hepatocellular necrosis Biliverdin is primary bile pigment – no assay commercially available Bile acids vary across reptilian taxa Renal Uric acid main excretory product of protein metabolism – produced in the liver (gout) Fasted samples required in carnivorous reptiles Uric acid main excretory product of protein metabolism – produced in the liver Fasted samples required in carnivorous reptiles – postprandial elevations Uric acid marker of renal disease, dehydration Persistent elevations can --> visceral & articular gout Reduced uric acid levels seen in hepatic disease Urea and creatinine less useful as low and variable levels May see elevated urea levels in early rehydration as can be resorbed across bladder wall Ca:P ratio one of most useful indicators of renal disease Sodium ↑ with dietary intake and dehydration and ↓ with renal disease, GI losses Other Calcium – egg laying females

Answer 308

Variations between carnivores & herbivorous species Liver & Muscle ALT elevations seen with hepatocellular damage so can be useful initial screening parameter AST found min muscle and liver so should be interpreted alongside SK ALP non specific for liver, elevated in young, growing animals or high bone turnover Calcium Rabbits unique amongst mammals in their Ca absorption mechanism Dietary intake can cause hypercalcaemia Renal Urea elevations as per other mammals with dehydration, renal disease, obstruction Can see hyper or hypcalcaemia Other Hepatic lipidosis  elevated trigycerides & cholesterol

Answer 309

Calcium leached out of bones Calcium and Vit D intake +/- UV exposure Must measure iCa as well as Total Ca Hypocalcaemia in African Grey Parrots Often collapse, seizures. Tremors iCa diagnostic Further lectures to cover this in more detail

Answer 310

Female birds and reptiles Classic pattern of biochemistry Constituents of egg and shell mobilised ↑ Total Protein, Globulin, Uric Acid, ALP, Total Calcium Check ionised calcium

Answer 311

Comparing human disease with that of animal models Animal models can be spontaneous or induced Spontaneous models in inbred mice are some of the most well known and technically simple The NOD (non-obese diabetic) mouse was discovered and established in Japan and is model for human type 1 diabetes mellitus. Induced can be chemical or genetic Streptozotocin given to rats is toxic to pancreatic beta cells, resulting in type 1 diabetes mellitus Genetic involves knock-in, knock out or transgenic mouse knock-in model generated to upregulate HER2, or the mouse orthologue Erbb2, in breast cancer

Answer 312

Refers to a type of arteriosclerosis (narrowing of vessels)- Composed of lipid, fibrous tissue, and calcium deposits in vessel walls Hugely important in human medicine and one of the major causes of coronary heart diseases (heart attack) Rare in animals Dogs Secondary to hypothyroidism, diabetes mellitus, and dogs with breed-related hyperlipidemia (Miniature Schnauzers) A recent study identified gonads of dogs as common locations for atherosclerosis, +/- amyloid deposits, associated with age and interstitial cell tumours (Ushio et al, Vet Pathol, 2021) Rabbits Chickens Pigs Nonhuman primates (NHPs) Rabbits are the most commonly used research species- Three types of rabbit model are commonly used for the study of human atherosclerosis and lipid metabolism: (Fan et al, Pharmacology & therapeutics, 2015)- Cholesterol-fed rabbits Watanabe heritable hyperlipidemic rabbits, analogous to human familial hypercholesterolemia due to genetic deficiency of LDL receptors, Genetically modified (transgenic and knock-out) rabbits

Answer 313

In contrast to other rodents, hamsters are naturally susceptible to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) As soon as angiotensin converting enzyme-2 (ACE2) was discovered as the principle human cellular receptor for the viral spike (S)-protein, systematic structural protein analyses of mammalian ACE2 homologs predicted that macaques, mink, ferrets, common marmosets, felines, rabbits, hamsters, and few other mammals but not mice would be naturally susceptible to the infection The Syrian hamster (Mesocricetus auratus) rapidly developed into a popular model. - It recapitulates many characteristic features as seen in patients with a moderate, self-limiting course of the disease such as respiratory tract inflammation and age dependence. Had already served as a model for SARS-CoV infection in 2005 The Roborovski dwarf hamster (Phodopus roborovskii) more closely mimics the disease in highly susceptible patients with frequent lethal outcome, including devastating diffuse alveolar damage and coagulopathy

Answer 314

Duchenne muscular dystrophy (DMD) is a progressive, fatal, X-linked monogenic muscle disorder Results in progressive muscle wasting. Caused by mutations in DMD, a gene encoding the protein called dystrophin In order to test treatments for DMD, a range of natural and engineered animal models have been developed, including mice, rats, rabbits, dogs, pigs.- There appears to be an effect of body size in models of DMD, as the severity of the clinical signs increases with increasing body size across species. All DMD models have different advantages and disadvantages The best known model is the dystrophic mdx mouse- 2800 papers published using this mouse Good biochemical model of DMD But, the mice have only a slightly shortened life span and show no obvious clinical signs of muscular dystrophy A number of different breeds of dogs presented at veterinary clinics have been diagnosed with dystrophin-deficient muscular dystrophy. - Several of these have been subsequently used to develop dog models of DMD The most common being a Golden Retriever with Muscular Dystrophy (GRMD) While these dogs do show clear clinical signs analogous with DMD, there are some significant differences. A number of the GRMD dogs die within the first 6 months of life and there is considerable dog-to-dog variation, which, with the small numbers available for each experimental group, makes it difficult to show clear statistically significant results The rabbit model is a recent creation using CRISPR/Cas9 - Rabbits have the advantage of being easier to breed and less costly than dog or pig models, but have clear clinical signs, in contrast to many mouse models.

Answer 315

identify the target- understand the disease validate the target- show that the target is clinically relevant ADME- Pharmacokinetics of agent Toxicity- is organ damage caused by agent? tolerabiluty- advere effects of behavioural agent? pharmacodynamic effect in target organ- agent engages target and causes clinically measurable effect

Answer 316

= immunodeficient mice engrafted with functional human cells and tissues It all started with the SCID mouse- Commonly known as the nude mouse Athymic due to a loss of function mutation in the PRKDC gene Resulting in impaired development of T and B lymphocytes which gives rise to severe combined immunodeficiency (SCID). The most common approach is to engraft human CD34+ hematopoietic stem cells which migrate to the bone marrow of the mouse and differentiate to all lineages of the mature immune system Some models involve whole body irradiation prior to engraftment Patient-derived xenografts in humanized mice- Not a new idea injecting human tissue into mice Orthotopic models involve implanting a human tumour into the corresponding tissue in animal models.- E.g. breast cancer cells directly into mammary tissue in mice Using a humanized mouse for this more appropriately models the tumour microenvironment, the contribution of the immune system to the eradication of tumour cells, and could predict drug response

Answer 317

Establish a diagnosis Provide prognostic information Guide selection of treatment or control strategies Monitor effect of treatments

Answer 318

Amplify the genome of viruses present in or released from infected cells DNA of bacteria, fungi or parasites

Answer 319

denaturing, anealing, extention Uses oligonucleotide primers to amplify region of interest (gene)- for specific antigen, toxin ect Cycles of heating and cooling drives each step Millions of copies can be produced in minutes Number of copies provides information on presence and/or amount of starting material

Answer 320

High temperature breaks hydrogen bonds holding base pairs together- 94ish ‘Melts’ double-stranded DNA revealing bases in specific order

Answer 321

At cooler temperatures, complementary bases can bind- 50ish Oligonucleotide primers ‘match’ small regions of the target area (gene of interest) They bind to the matching areas (anneal) Primers must be designed so that one matches the sense strand and the other matches the antisense strand

Answer 322

Temperature raised to approximately 74°C Synthesis of new complementary DNA strand from 3’ end of primer Only regions where primers bound will be amplified/copied. So it’s really important that they only match the region we’re interested in

Answer 323

In one cycle (denaturation; annealing; extension) we have gone from one copy to two Cycle is repeated multiple times and product number increases exponentially Average PCR run is 40 cycles

Answer 324

The amount and size of the PCR product can be visualised using staining and gel electrophoresis This visually confirms if our pathogen / gene of interest / strain is present Known as semi-quantitative PCR

Answer 325

the amount of DNA amplified in each cycle are quantified. increased florecence indicates increased presesnce of target targrt floreced via cyber green or Taqman TaqMan more specific- floreces when "knocked off" target stran d of dna by formation on new strand

Answer 326

This value tells how many cycles it took to detect a real signal from your samples. the point in qPCR where a flourecent signal is detectable

Answer 327

Uses reverse-transcriptase enzyme to produce double stranded DNA from RNA This provides template for normal PCR Can also be incorporated into qPCR = RT-qPCR

Answer 328

very useful Serological assays are not always feasible when detecting viral infections so PCR can be used Lack of species-specific secondary antibodies Suitable cells for growth and titration are not available primer needs to be developed

Answer 329

Culture- labour intensive, can take long time, contamination of culture common, multiple plates and culture mediums may need to be used Stain Test not useful for, for example: Helicobacter- Many different species that can infect veterinary species- which one do u culture? which one is actually casing disease Individuals can be infected with more than one species at the same time Fastidious bacteria (difficult to culture)

Answer 330

Many different species that can infect veterinary species Individuals can be infected with more than one species at the same time Fastidious bacteria (difficult to culture) PCR primers designed to detect a single species Rapid test

Answer 331

Slow growth in culture Diagnosed histologically Can be diagnosed with PCR PCR can be used if no identifiable fungal species cultured or morphologically identifiable Pathogen-specific primers Generic fungal primers (e.g. rRNA) Genus-specific primers

Answer 332

Specificity is very high- primers can be designed to be incredibly specific Sensitivity is very high- you cna have very little dna and it will work (some assays are still more sensitive though- giardia assay duse to fecal sample having pcr inhibitors Rapid turnaround time Overcomes culturing restrictions

Answer 333

PPV can be low Not for all assays/samples Requires specialist equipment Overcomes culturing restrictions

Answer 334

The probability that a test positive animal is diseased Disease agents may colonise healthy animals as well PCR detects DNA/RNA in live and dead organisms May be positive even if infection is controlled or cleared Interpretation of results for a single animal can be difficult

Answer 335

False negatives present a challenge Often occur due to PCR inhibitors in the sample Natural inhibitors include: Bile salts Polysaccharides in faeces Haem from blood Glycogen and fats in tissues Proteinases in milk Urea in urine to combat this there are: Co-purified with DNA/RNA Extraction kits designed to remove them

Answer 336

Detection of organisms gives most information Assays not always available or optimal Antibody detection still commonly used Combinatory approach can be used PCR positive result can occur prior to seroconversion – prove infection in acute cases PCR can be negative later in course of disease Serum antibodies are detectable

Answer 337

Detect antibodies or antigen in blood sample Indirect method Limitations due to lack of species-specific secondary antibodies Seropositivity may not indicate acute infection

Answer 338

Specific portion of pathogen Protein found on surface of pathogen Non-self

Answer 339

Proteins (immunoglobulins (Ig)) Part of the immune system (self) Created to bind to specific antigens Specific antigen binding sites The most common antibodies have 2 binding sites, some have 4 or 10 Binds to antigen Neutralises antigen

Answer 340

2 types of ELISA: Direct test - Antibodies used to test for antigen Indirect test – Antigens used to test for antibody Can test for: Bacteria or bacterial toxins Viruses Protozoa Ab to any of these or Ab to parasites, yeasts,

Answer 341

Antibodies used to test for antigen Sample proteins immobilised on plate/well Enzyme labelled antibodies added Antibodies bind to antigen Enzyme-specific substrate added Reaction takes place and produces colour Colour change (signal intensity) detected

Answer 342

Antigens used to test for antibody

Answer 343

Detection of antibody: Antigen immobilised on plate/well Sample is added Any antibodies present will bind to antigen Enzyme-labelled secondary antibody added Substrate added Reaction takes place and produces colour Colour change (signal intensity) detected

Answer 344

Detection of antigen: Plate/well coated with capture antibodies Sample is added Any antigen present will bind to antibody Direct: enzyme-labelled antibody used Indirect: Enzyme-labelled secondary antibody added Substrate added Reaction takes place and produces colour Colour change (signal intensity) detected

Answer 345

multiple ways to set up depending on whether the antigen or antibody is of interest Detection of antigen or antibody: Sample antigen/antibody competes with reference antigen/antibody Analyte concentration is indicated by signal interference Coat plate with reference antigen Incubate sample (unknown antigen concentration) with limited amount of labelled antibodies Low antigen conc. in sample = large portion of labelled antibodies have nothing to bind to Add this mixture to the antigen coated plate Any free labelled antibodies will bind to reference antigen Wash plate to remove antibodies bound to sample antigen Add substrate Stronger colour = less antigen present in sample

Answer 346

Plate coating: Samples are diluted in buffer, then pipetted into a microwell plate. After incubation, the solution is discarded and plate is washed with a wash buffer. ONLY immobilised antigen/antibody remains Plate blocking: Blocking buffer is added to the plate. This binds to any remaining protein-binding sites in the coated wells, reducing non-specific binding of antibodies to the plate. Plate then washed again Antibody incubation: Following incubation, wash away unbound antibodies with a wash buffer. Detection: The enzymes covalently attached to the antibodies will start producing a coloured reaction product. Stop solution is added to terminate the colour development and the absorbance of each well is read. The signal intensity allows you to determine whether a sample contains the antigen/antibody of interest, and at what concentration. By stopping all wells at the same time (with stop solution) the signal intensity if indicative of the antigen (or antibody) concentration.

Answer 347

ELISA Detect the presence of a target substance (antigen) in a liquid sample ‘Signal’ is still a colour change But does not require specialised equipment (patient-side) Chromatography paper = capillary action Antigen binds to antibodies with tag Flow along test paper Collect at test line – fixed antibodies that will bind to antigen(Collection = visible line) Flows across control line – fixed antibodies that bind to tagged antibodies Detection of signal indicates detection of antigen-antibody complex

Answer 348

All endoderm and some ectoderm Cells form bulk of parenchyma of organ, glands or line organs Hepatocytes Skin GIT Bladder Cell-to-cell and cell-to-basement membrane adherence

Answer 349

Mesoderm Supporting cells Fibroblasts -> collagen Endothelia Bone

Answer 350

Mesoderm Cells of the haemo-lympho system Erythrocytes Leukocytes

Answer 351

Polygonal Poorly-defined cell borders Abundant cytoplasm Polar to central round nuclei Basement membrane

Answer 352

Fusiform/spindloid- long, stringy Poorly-defined cell borders Variable cytoplasm Fusiform/spindloid nuclei Extra cellular matrix

Answer 353

Round Well-defined cell borders Individualised Variable cytoplasm Round to variable nuclei

Answer 354

Immunodiagnostic Uses antibodies to detect an “antigen” in a tissue IHC can be used to differentiate between inflammation and neoplasia A classic example is inflammatory bowel disease versus lymphoma In both diseases lymphocytes accumulate in the intestine If inflammatory this is polyclonal Multiple lymphocytes replicating If neoplastic this is monoclonal One cell becomes neoplastic and replicates Antibodies made by injecting antigen of interest into an animal Two types of antibodies Monoclonal Antibodies produced by the same clone of plasma B cells Hybridisation with tumour cells Higher specificity, lower sensitivity Polyclonal Heterogeneous mix of antibodies Derived from the immune response of multiple B-cells Each one recognizes a different epitope on the same antigen Higher sensitivity, lower specificity

Answer 355

Epithelial cells

Answer 356

Mesenchymal cells

Answer 357

Proteinuria Acute renal failure Chronic renal failure Renal azotaemia that cannot be categorized as acute or chronic renal failure

Answer 358

the presence of abnormal quantities of protein in the urine, which may indicate damage to the kidneys. Proteinuria is, once a urinary tract infection is ruled out, almost always due to disease of the glomerulus. Whereas low urine specific gravity, which would indicate reduced ability to concentrate urine, is typically due to disorder of the tubule.

Answer 359

The structure of the glomerular capillaries is important in determining the rate and selectivity of glomerular filtration. The glomerular capillary wall consists of three layers: the capillary endothelium the basement membrane the visceral epithelium = podocyte Greek pous, pod- ‘foot’

Answer 360

Results from the deposition of immune complexes in glomeruli formation of antibodies against the glomerular basement membrane activation of inflammatory cascade Any condition that stimulates the immune system for long periods of time can cause IM-glomerulonephritis

Answer 361

Microscopic examination of tissue samples spread onto slides Histology looks at architecture, cytology has no architecture - look at individual cell morphology Aspirates – solid tissue Needle only Intermittent suction Continuous suction Impression smears - mucosa, ears, biopsies Wash / Lavage – trachea, BAL, nasal, prostate Ultrasound guided – watch out for ultrasound / lubricant gel! No anaesthetic and low risk of complications Relatively quick procedure and less invasive Rapid results – emergency cases, clients waiting, same day intervention Older patient - removal of a benign tumour? Grading of tumours to he lp with surgical or chemo planning Surgical planning Staging of tumours Fluid classifications – Transudate, Modified Transudate, Exudate Infections (septic abdomen, ear cytology) Ancillary tests- PARR analysis and Flow Cytometry PCR for infectious diseases

Answer 362

22-gauge needle 5-10ml syringe Glass slides Pencil place needle without syringe in mass- not in purilent area rediredct needle a few times take out needle put air filled syringe on needle and put needle over slide squirt cells down onto slide suction technique- same but pit syringe on first and apply suction while in mass may cause haemodilution the sample must then be spread- Squash pull / drag method best, send both slides Fluids- Blood smear (push / wedge) Line concentration Cytospin

Answer 363

Submission forms Formalin Sample types used for fluid Lubricant gel Cellularity / Pre-staining Preservation Cell thickness Greasy slides

Answer 364

Exposure of unfixed cytologic specimens & air-dried unstained smears to formalin fumes → Interferes with staining

Answer 365

BAL Pleural or Abdominal fluid Prostate wash Urine – sediment vs. cytology- diffretn things!!!!. braf test for transitional cell carcinoma Bile-most samples you see nothing but cats get bacterial infections Cerebral Spinal Fluid One or more direct preparations Air dried and submitted with fluid EDTA (cyto) and plain tubes (culture) Fluid is a very poor preservative - cells deteriorate very quickly in fluid. could be done for FIP

Answer 366

The number of cells in a given tissue sample How to assess this before sending to the lab? Pre-staining- can effect labs staining Assessment of unstained slides = lower the condenser

Answer 367

Lipoma? Other differentials include: Steatitis / panniculitis Perinodal fat Mast cell tumour Liposarcoma Other soft tissue sarcoma Not representative Sample preparation – allow to dry and stain flat

Answer 368

Diff-Quik stain consists of: Fixative agent - methanol, blue Solution I - eosinophilic, orange Solution II - basophilic, blue Technique Dry slides in the air Dip slides sequentially into each solution 5 times (one second each dip) After every immersion wait a moment to drain excess. Rinse with tap water Allow to dry (do not use heat sources) Slides must be air-dried before staining – it is important to make sure the slides are very dry before staining, water may still be present when the slide appears dry – so make sure to leave sufficient time for adequate drying. Heat fixation is not recommended as this may interfere with staining quality and can rupture cells. When using diff quick dip slides into each solution 5 times for 1 second, followed by a water rinse and dry the slide vertically Some tips for the ideal stain include: If the slides are thin or have only a few cells on them - shorten staining times Thick smears or those with high protein may need longer staining times. Ensure stain reagents are fresh and well maintained - if your cytology slides have a lot of stain precipitate on them , it is probably time to refresh the stain. If you get a gold film forming on the top of the stain – this means it is also time to change the reagents Organisms in the stain may contaminate the cytological slides. Automatic staining – external lab may make mast cells look like histeocytoma!!!!!

Answer 369

new! better than diff quick May-Grunwald Giemsa Quick stain Performs similar to the traditional May Grunwald-Giemsa used in labs But is quick to perform like most rapid stains Technique Dry slides in the air Dip slides sequentially into each solution 5 times (one second each dip) After every immersion wait a moment to drain excess. Rinse with tap water Allow to dry (do not use heat sources)

Answer 370

Modified Wright’s only material in middle of lide is stained so slides must be preped appropriatly

Answer 371

Get your slides out ready Ensure you never put any slides you have taken out of the box back in the box – avoids cross contamination If doing needle only attach the syringe over the slides Always start with needle only to ensure you don’t get too much blood contamination Never package with formalin Always submit more than one slide Don’t put cytology slides in the fridge- erythrocytes can freeze Avoid using a hairdryer or flame to dry- cells rupture and fragment Greasy slides need longer to dry and should be stained flat Make sure you use fresh stain

Answer 372

Cellularity and preservation Haemodilution Inflammatory or Proliferative Inflammation – infectious, immune mediated, necrosis Proliferative type Epithelial, Mesenchymal, Discrete / Round cell, neuroendocrine Hyperplastic, dysplastic or neoplastic Neoplasia – benign or malignant Definitive diagnosis

Answer 373

Erythrocytes Platelet Clumps Nucleated cells in peripheral blood- are they from mass or just from the haemodilution??? neutrophils and monocytes- from blood macrophage- from tissue eosinophils and basophils lymphocytes

Answer 374

White blood cells- Neutrophils, macrophages, eosinophils, lymphocytes, mast cells (a couple are OK). Neutrophils- Non-degenerate neutrophils – well preserved Degenerate neutrophils – microorganisms and necrosis. Pale blue swollen nucleus Macrophages- Activated - vacuolated and foamy Phagocytosis –fresh smear as can do this in vitro Infectious agents (Slow growing bacteria, Fungi, Parasites Cell debris Erythrophagia - previous haemorrhage, breaksdown to haemosiderin and haematoidin

Answer 375

a benign nodular lesion, histopathologically characterized by marked proliferation of non-neoplastic, polyclonal lymphocytes forming follicles with an active germinal center. you will see: Mixed small, intermediate, large lymphocytes Mott cells Plasma cells

Answer 376

Inflammation - Acute / suppurative - neutrophils Chronic active / pyogranulomatous – neutrophils and macrophages Chronic / granulomatous – macrophages (multinucleated), lymphocytes, plasma cells Specific e.g. eosinophilic Concurrent tissue reaction – hyperplasia / dysplasia Infection- Bacteria – rods / cocci / coccobacilli Yeasts and fungi Mycobacterium Protozoa

Answer 377

Higher than expected cellularity Cells may display some mild criteria of malignancy Mildly increased N:C ratio Darker blue cytoplasm More prominent nucleoli Finer chromatin than normal

Answer 378

Nuclear to cytoplasmic asynchrony Increased cytoplasmic basophilia Anisokaryosis and anisocytosis. Dysplasia can be cytologically difficult to distinguish from neoplasia as dysplastic lesions often contain more criteria of malignancy than strictly hyperplastic lesions.

Answer 379

Epithelial Mesenchymal Round Cell Neuroendocrine

Answer 380

Arrangement- Monolayer sheets, clusters, rows, palisades and acinar. Cohesive with distinct tight junctions (desmosomes) Clear lines between cells. Shape Columnar, cuboidal or polygonal Nuclei Round to oval. Epithelial cells can look round in fluid or when poorly differentiated. E.G.: Squamous cell carcinoma, adenoma and adenocarcinoma Benign: Adenomas Malignant: Squamous cell carcinomas

Answer 381

Arrangement Often see individual cells but occasionally seen in aggregates. Loosely arranged with extracellular matrix and individualised spindle or stellate cells. Shape "Spindle cell" - spindle shaped cells, fusiform or stellate. Wispy cytoplasmic borders, the borders are not distinct. Cytoplasm can contain vacuoles Nuclei Round to elliptical (oval). Cytoplasm can contain vacuoles. Samples are often poorly cellular in benign lesions, but can be very cellular in malignancy. Arise from connective tissue e.g.: fibroblasts, osteoblasts, adipocytes, myocytes and vascular lining cells. E.g Osteosarcoma, Haemangiosarcomas etc. Benign: Fibromas, lipomas Malignant: Sarcomas, soft tissue sarcoma, haemangiosarcoma etc.

Answer 382

Greasy slides Large fat filled adipocytes in aggregates Often have capillaries going through them Often benign, can have infiltrative forms Liposarcoma - malignant version

Answer 383

Arrangement- Discrete and individually arranged Shape- Round tumour cells Well defined / distinct cytoplasmic borders Nuclei- Round to oval large nucleus (can be indented) Exfoliate well 5 main examples: Mast cell tumour Lymphoma / leukaemia Histocytoma / histiocytic sarcoma Plasma cell tumour / plasmacytoma / multiple myeloma Transmissible venereal tumour

Answer 384

Round cells Central round nuclei Lots of magenta granules in the cytoplasm Fibroblasts, eosinophils and ribbons of pink matrix

Answer 385

Monomorphic population of lymphocytes individually arranged Low N:C ratio Large cell vs. small cell lymphoma Lymph nodes, skin, spleen, intestines

Answer 386

Rounds cells individually arranged Light blue cytoplasm, Nuclei round to oval to cleaved Often accompanied by lymphocytes and plasma cells Mass in a young dog, likely histiocytoma, although can get them in older dogs

Answer 387

Rounds cells individually arranged Looks like well differentiated plasma cells, however the cells are predominantly plasma cells. If this was reactive you would see a mix of lymphocytes and plasma cells Prominent golgi zone Multinucleation and Macronuclei even though commonly benign

Answer 388

Used to be a rare disease in the UK Seeing more and more cases Sexually transmitted tumour is thought to be of histiocytic origin - transfer of intact neoplastic cells Often around the mouth or genital region, but can be seen in other sites. Cytoplasm is characteristic: Abundant light blue to grey with moderate to many discrete margined vacuoles CTVT cells have 59 chromosomes compared with the normal canine karyotype of 78 chromosomes. PCR now available to help diagnosis

Answer 389

Arrangement- Free nuclei arranged in small rosettes / sheets Shape- No cytoplasm – mostly just bare nuclei Nuclei Round Exfoliate well Examples: Thyroid tumours, pheochromocytomas

Answer 390

Identification: Nuclear features Cytoplasmic features Miscellaneous- Background – joint fluid, product, mucous, chylous Haemodilution – inflammatory? Accompanying cells – contamination or tissue? Concurrent process – haemorrhage, inflammation, necrosis Presence / absence – e.g. lymphoid cells When looking at a slide it is important to be systematic- Always start at the top left of the slide. Scan the slide at low power (4x magnification) Assess the cellularity, background colour and then find the main cellular population Then get closer at 40-100x Careful to not get oil on the 40x! it is important to appreciate certain nuclear features. Bizarre mitotic figures are often very interesting and can really help you determine whether a lesion is neoplastic. In this example here the mitotic figure is very atypical and has become fragmented. You can have multinucleate cells with different sized nuclei within the same cell. Also large prominent nucleoli are a key feature to look out for.

Answer 391

Size and shape Chromatin Nucleoli Nuclear membrane Relationship / nuclear moulding Mitotic figures

Answer 392

Vacuolation Basophilia Product N:C ratio Nuclear position

Answer 393

Anisocytosis and Anisokaryosis Increased nuclear to cytoplasmic ratio (not always seen e.g.: lymphocytes) Nuclear features: Mitotic figures, how many there are and if they are atypical Multinucleation Nuclear moulding Angular nuclei Chromatin (instead of being smooth it becomes coarse and clumped) Nucleoli: Prominent, multiple, angular, anisonucleoliosis Macrocells, macrokaryosis and macronucleoli - macro is always bad news! Necrotic cells in between neoplastic cells. These cells look like smudge cells (been rubbed out with a rubber) Phagocytosis - cannibalism Emperipolesis Crowded cells

Answer 394

Features of the abnormally represented population: Small, intermediate or large lymphocytes Blastic appearance (presence or absence of nucleoli) Position of the nucleus in the cell, eccentric or central Shape of the nucleus, round, oval, cleaved, convoluted Relative volume of cytoplasm Appearance of cytoplasm, eccentric, concentric, mirror-handle Presence/absence of golgi zone Relative numbers of mitotic figures and presence of atypical mitoses Dimorphic lymphocyte distribution Presence of ancillary cells, tingible body macrophages, eosinophils Careful cytological assessment will efficiently diagnose lymphoma and allow estimation of the classification, phenotype and grade Cells harvested for cytology are not formalinised allowing molecular and immunological investigation of stained slides The big 5 canine lymphomas have characteristic cytological patterns recognisable to skilled cytologists, allowing a quick and cost effective diagnosis. On cytology you can see: Disproportionate representation of a specific lymphocyte population – In general lymph-nodes should be heterogenous, but instead in lymphoma you have a homogenous effacing population Cytology also allows you to see very fine cellular details of the neoplastic population such as the chromatin pattern and atypical mitotic figures.

Answer 395

PARR analysis Assessment of clonality (genotype) Clonality Testing (PCR for antigen receptor rearrangement; PARR) uses end-point PCR to predict whether lymphocytes in a sample are a clonal or polyclonal population Flow cytometry Assessment of phenotype Immunocytochemistry Assessment of phenotype

Answer 396

Don’t crush it- think about handling, dont handle critical areas, can distort tissue- lymphoid tissie and tumour cells vunerable to this •Don’t cauterise it •Don’t freeze it •Don’t scrape mucosal surfaces (e.g. GIT)- rinse under water instead if needed •Fix it ASAP! Don’t package cytology and histology together

Answer 397

sample pots- Label your sample pots- important! wha tis the sample! •Use appropriate containers •Use correct amount and type of fixative •10:1 ratio of formalin: tissue •10% neutral buffered formalin dont use- Narrow-necked bottles “pill pots”- sample may swell when fixed Glass containers- health and saftey Sharps container- cant open!

Answer 398

Cross-sectional or radial •Bread loaf or pie Cost effective •Easy •Allows for measurement of margins •Assumes centrifugal growth from centre •Only evaluates a portion of marginal tissue Tangential / shaved / orange peel •Tumour bed •Theoretically complete assessment of all marginal tissue •Technically difficult •More slides, more cost •Does NOT allow measurement of margins •Binary answer –excision complete or not suture tags can be used to comunicate thing to pathologist you can also ink the sample- green and blue ink best

Answer 399

Heart disease is any condition affecting the cardiovascular system - chronic in nature e.g. cardiomyopathy - acute in nature e.g. myocarditis - may or may not have clinical signs associated with it e.g. syncope, exercise intolerance - abnormalities on physical examination usually present e.g. heart murmur Heart failure is a syndrome where the heart can no longer meet the metabolic demand of the body - Usually acute onset - Clinical signs present e.g. exercise intolerance, syncope, lethargy, anorexia etc. - Physical examination abnormalities present e.g. fluid thrill, dyspnoea, crackles, jugular pulsation etc.

Answer 400

Often non-specific/ absent Exercise intolerance and weakness Can be syncope/ pre-syncope Cyanosis Coughing- left atrium can press on brochi. fluid could fill in lungs, Paresis-condition in which muscle movement has become weakened or impaired. thrombi can be lodged in aorta. thrombi can aso cause lamness (acute blindness, neurologic signs) on physicla examination: Body condition score Respiratory rate and effort Ascites- condition in which fluid collects in spaces within your abdomen Distended jugular Pulsating jugular Peripheral oedema Cyanosis Right to left shunting defect from deoxygenated circulation to oxygenated Central cyanosis Differential cyanosis Peripheral cyanosis Heart murmur (dog vs cats) Arrhythmia (dogs vs cats)- cats is assosiated with heart disease but more varied differential with dogs Gallop sound Cat with cold hindlimbs Cyanosis Presence of goitre Retinal detachment Some neurological signs

Answer 401

Tachypnoea/ dyspnoea (L CHF usually) Weight loss (less cats) Swollen abdomen (R CHF) Peripheral oedema (R CHF) Signs as per heart disease mm often normal!!! Dyspnoea/ tachypnoea Crackles in lungs Ascites (fluid thrill) Jugular distension Significant jugular pulsation Muffled heart or lung sounds Positive hepatojugular reflux Pulsus alternans/ paradoxus Peripheral oedema Plus usually signs of heart disease

Answer 402

Normally only 1/3 up neck If to angle of jaw – abnormal Arrhythmias Tricuspid regurgitation Pericardial disease

Answer 403

Should collapse after pressure released Elevated systemic venous pressure R heart failure Pericardial disease Obstruction of cranial vena cava Hypervolaemia (cats)- fluid overload, is a condition where you have too much fluid volume in your body

Answer 404

Auscultation- Heart – both sides thorax, apex and base Heart murmur Gallop sounds Arrhythmia – Atrial fibrillation, AVB… Heart rate – brady/tachyarrhythmias All lung fields Compare sides and dorsal vs. ventral Muffled Crackles Palpation/ percussion/ compression- Apex beat displaced Thrill Percussion for fluid/ soft tissue/ air Reduced compressability (cats)

Answer 405

Normally heard in dogs and cats- Occur during systole S1 ‘lub’ Closure of AV valves S2 ‘dub’ Closure of semilunar valves Not normally heard in dogs and cats- Gallop sounds (occur in diastole) S3 Early diastolic filling Not heard in compliant ventricle Systolic dysfunction S4 Atrial contraction Forceful atrial ejection into a noncompliant ventricle Hypertrophic/ restrictive cardiomyopathy

Answer 406

Palpation- Fluid thrill – ascites Splenomegaly occasionally CHF Hepatomegaly too Painful sometimes Hepatojugular reflux- Squeeze just behind ribs Watch jugular vein If jugular vein distends whilst squeezing – positive response Positive response suggests high R sided filling pressure R side can’t accommodate extra blood

Answer 407

Alternates strong with weak Myocardial failure

Answer 408

Decrease pulse quality on inspiration Pericardial effusion

Answer 409

Extra sound Occur during systole (most commonly) – between ‘lub’ and ‘dub’ Or diastole – after dub Or both (continuous murmur) – all the time Due to regurgitation of blood e.g. mitral regurgitation OR turbulent flow across a narrowing e.g. sub-aortic stenosis, VSD OR reduced viscosity of blood (anaemia) Blood flows DOWN pressure gradient High pressure – low pressure The greater the gradient the faster the flow Depending also on resistance to flow Flow ONLY occurs when a pressure difference exists Can explain many phenomena: PDA – continuous murmur (L-R shunting) Murmurs on right often quieter than left VSD shunts L-R ‘normally’ Reverse shunts tend to be quieter

Answer 410

Grade 1 – barely audible, need quiet room 2 – audible but quieter than heart sounds 3 – clearly audible and as loud as heart sounds 4 - louder than heart sounds 5 – THRILL (PALPATION) present- buzzing feeling of chest 6 – Audible with stethoscope lifted off chest Mild/ moderate/ loud/ thrilling (Ljungvall 2014) Timing Systolic/ diastolic/ continuous Can be further classified as holo- and pansystolic Location Right/ left Apex/ base (dogs) Sternal/ parasternal (cats) Radiation- does it radiate dorsaly? to the left? ect

Answer 411

Mitral regurgitation- Grade can correlate with severity (MMVD not DCM) Pansystolic worse (MMVD) Can be musical/ whooping Often radiates to right Tricuspid regurgitation- Difficult to distinguish from radiating left sided murmurs Vary with respiration Tricuspid valve dysplasia Pulmonary hypertension Degeneration of valve

Answer 412

Aortic stenosis- Harsh sounding Radiate widely to thoracic inlet Low grade are difficult to distinguish from physiologic/ innocent (Cats – HOCM dynamic) Pulmonic stenosis- Left heart base Radiate dorsally

Answer 413

Innocent- Puppies and kittens No structural heart disease Grade 1-3 Systolic Left heart base Don’t radiate widely Functional- Associated with disease process Anaemia Hyperthyroidism Fever Hypertension Pregnancy No structural heart disease Grade 1-3 Systolic Left heart base Don’t radiate widel

Answer 414

Ventricular septal defect (VSD)- Usually left to right Smaller defect louder murmur Right sternal border Increased right side pressure Quieter Bi-directional Right to left Absent Atrial septal defect (ASD)- Murmur not directly related to ASD Only large defects Increased blood flow Relative pulmonic stenosis Left heart base

Answer 415

Aortic regurgitation- Heart base Quiet Endocarditis/ congenital Early closure of MV – Austin flint murmur - severe Pulmonic regurgitation- Uncommon Left base Pulmonary hypertension Mitral stenosis- Rare Left apex Mid-diastole

Answer 416

Patent ductus arteriosus (PDA) Loudest heart base Radiate to thoracic inlet MISS THEM if only auscultate apical region Other causes very rare

Answer 417

Depends on clinical sign/ physical examination finding Respiratory disease – cyanosis, dyspnoea/ tachypnoea, muffled heart sounds, crackles, dull percussion, cough, syncope Neoplasia – ascites, muffled heart sounds, dyspnoea/tachypnoea, dull percussion, weakness Hypoproteinaemia – ascites, muffled heart sounds Neurological disease – paresis, paralysis, weakness, syncope Metabolic disease – syncope, weakness, tachypnoea

Answer 418

Symptomatic – tachypnoeic/ dyspnoeic, syncopal, exercise intolerant, cyanotic etc. Pyrexic and new murmur Small breed dog with grade 3/6 or louder left apical murmur (MMVD) Breed predisposed to DCM with an apical murmur (remember Cocker spaniels too) Intended for breeding/ athletic activity Grade 3/6 or louder murmurs over heart base ANY diastolic murmur ANY continuous murmur

Answer 419

Symptomatic – tachypnoeic/ dyspnoeic, syncopal, exercise intolerant, cyanotic etc. Pyrexic and new murmur Breeds predisposed to HCM e.g. Sphynx, Ragdoll, Toyger, Persian, Maine Coon, Bengal etc. ANY diastolic murmur (too fast to tell?) ANY continuous murmur Arrhythmia Gallop sounds Murmur intensity less useful in cats!

Answer 420

Blood pressure Blood tests- CBC, biochem, electrolytes NT-proBNP- released form heart when it streaches Cardiac troponin I- use for hf hd and arhythmias, released when cardiomyocyes break down ECG- (Holter monitor) (Loop recorder) Thoracic imaging- Radiography Echocardiography (CT)

Answer 421

Gold standard approach: Bloods (NT-proBNP, cardiac troponin I in certain situations) Blood pressure ECG Echocardiography (in-house vs referral) Thoracic radiography? If financial concerns: ECG if arrhythmia Echocardiography (likely in-house) Just NT-proBNP? Just thoracic radiography?

Answer 422

Is the sample haemolysed/lipaemic/icteric? Has my sample been taken/handled properly?- Clotted? Artefacts can occur if not stored properly Serum should be separated/spun soon after collection Too much or too little sample? Contamination by anti-coagulant Delay

Answer 423

Antigen versus antibody Most useful test?- FNA in canine mammary tumours vs FNA in canine diffuse large B-cell lymphoma in a lymph node More than one test: e.g Cushing’s: CBC and biochem Urine cortisol:creatinine ratio Basal cortisol ACTH-stim test Low-dose dex suppression test High-dose dex suppression tes Imaging

Answer 424

Changes in the distribution of fluid between the plasma and interstitium are most commonly manifested as oedema, which is defined as accumulation of excess interstitial fluid. Occurs by: increased microvascular permeability increased intravascular hydrostatic pressure decreased intravascular osmotic pressure decreased lymphatic drainage

Answer 425

inflammation Inflammatory mediators will result in the release of cytokines: interleukin 1 (IL-1) tumour necrosis factor (TNF) interferon-γ Resulting in endothelial cell retraction and widening of interendothelial gaps. Microvasculature permeability

Answer 426

Increased flow or volume of blood hyperaemia (active) congestion (passive)

Answer 427

Osmotic (colloidal) pressure- Maintained by plasma proteins, particularly albumin Albumin can be decreased due to: Reduced production- Severe liver disease, Protein starvation Increased losses- GI disease-protein losing enteropathy, parasitism Renal disease- protein losing nephropathy

Answer 428

Lymphatic obstruction or compression Congenital lymphatic aplasia or hypoplasia Intestinal lymphangiectasia Lymphangitis- jhones disease

Answer 429

Same mechanisms as oedema but into a larger space or cavity Tap it! Blood, bile, urine or GIT content? Transudate, modified transudate or exudate Cytology

Answer 430

extravascular fluid with low protein content (Total protein (g/dL)- <2.5) and a low specific gravity (< 1.012) It has low nucleated cell counts (Nucleated cells (x103/ul)- <1.5) Transudates develop most commonly as a result of decreased plasma osmotic pressure. can be caused by Hypoalbuminaemia.

Answer 431

an effusion that occurs by transudative mechanisms where vascular fluids leak out of “normal” or “noninflamed” vessels (e.g. via increased capillary hydrostatic pressure or lymphatic obstruction). Total protein (g/dL)- >2.5 Nucleated cells (x103/ul)- <5 Develops in response to increased hydrostatic pressure or permeability of capillaries and/or lymphatic vessels. Causes- Cardiac disease, neoplasms, hepatic disease, and feline infectious peritonitis.

Answer 432

fluid that leaks out of blood vessels into nearby tissues. The fluid is made of cells, proteins, and solid materials. Exudate may ooze from cuts or from areas of infection or inflammation. It is also called pus Total protein (g/dL)- >4 Nucleated cells (x103/ul)- >5 Develop because of increased vascular permeability caused by inflammation. Non-septic exudates are caused by irritants such as bile, urine, and pancreatic enzymes or because of tissue necrosis. Neutrophils in such effusions are nondegenerate. Septic exudates are caused by microorganisms which may or may not be evident cytologically.

Answer 433

a test for FIP using effusion To perform this test, a transparent test tube (volume 10 mL) is filled with approximately 7–8 mL of distilled water to which any one of the following is added: one drop (20–30 μL) of acetic acid (98–100%) OR 2-3 drops 25% white vinegar OR 10 drops of 5% white vinegar and mixed thoroughly. On the surface of this solution, 1 drop of the effusion fluid is carefully layered. If the drop disappears and the solution remains clear, the Rivalta's test is defined as negative. If the drop retains its shape, stays attached to the surface or slowly floats down to the bottom of the tube (drop- or jelly-fish-like), the Rivalta's test is defined as positive.

Answer 434

vascular abnormalities caused by degenerative, metabolic and inflammatory conditions, embolic diseases, coagulative disorders, and functional disorders

Answer 435

inflammation of the blood vessels/vasculature

Answer 436

inflammation of arteries

Answer 437

inflammation of veins

Answer 438

inflammation of lymphatics

Answer 439

narrowing of vessels

Answer 440

narrowing of vessels due to deposition of fatty material in vessel walls

Answer 441

Hypovolaemic Cardiogenic Distributive Hypoxic (Obstructive)- rare, and falling out of fashion

Answer 442

HYPOPERFUSION AND/OR CELLULAR ANAEROBIC CONDITIONS resulting in HYPERLACTERAEMIA

Answer 443

results from Impaired oxygen delivery to the cells e.g Anaemia Decreased haemoglobin saturation – carbon monoxide. carbon monoxide has greater affinity for haemoglobin than oxogen so takes up the haemoglobin instead of the oxygen Respiratory disease

Answer 444

most common form of shock fluid lost form intravascular space comon caues- acute blood loss sever dehydration third spacing- fluid comes form intravascular space into the intrasticial space due to loss of protien and oncotic pressure- e.g protien loosing enteropathy, parvo

Answer 445

heart doesnt function properly- weak contractions could be caused by damage to the myocardium- dilated cardiomyopathy pulses may not match the heart rate

Answer 446

inflamitory markers cuase vessels to become less receptive to constrictive elements and then reamian dilated in situations in which they'd normally constrict Systemic inflammatory responses (SIRs)- Heat stroke Sepsis may cause cold extremities- freezing mucus membranes

Answer 447

cold extremities cold mucus membranes Increased lactate Metabolic acidosis Mucous membrane colour change- pale exept for distributive shock Weak pulses Increased heart rate (Dogs) or decreased heart rate (cats)

Answer 448

could be caused by GDV ondition that prevents blood and oxygen from getting to your organs

Answer 449

Hypovolaemic shock- third spacing Cardiogenic shock Obstructive shock Distributive

Answer 450

lactate faling with treatment = good prognosis

Answer 451

the formation of: Erythrocytes Leukocytes Platelets Typically occurs in the bone marrow but extramedullary haematopoiesis also occurs in the spleen and liver The thymus is responsible for T-lymphocyte maturation- Compare the Bursa in birds Lymph nodes: Not present in birds Filter lymph for antigen presentation and response Clinical signs associated with disorders of the haemolymphoid system: Enlarged lymph nodes Anaemia Coagulopathies Oedema

Answer 452

Enlarged lymph nodes Causes of lymphomegaly: Reactive- Reactive lymphoid hyperplasia. reacting to infection in other areas. the lymphnode affected depends on the sites that drain into it Inflammation/infection- Lymphadenitis Neoplastic Diagnostic tools: FNA- Avoid those lymphnodes draining the mouth Biopsy Questions for the pathologist: One cell predominates or mixed? Which cells are there more of? Regular or irregular? Maintenance of tissue architecture? Necrosis?

Answer 453

Congenital immunodeficiencies Viral infections Cachexia/malnutrition Aging Radiation and chemotherapy Toxins

Answer 454

Hematopoietic tissue is highly proliferative. Pluripotent hematopoietic stem cells (HSCs) are a self-renewing population, giving rise to cells with committed differentiation programs, and are common ancestors of all blood cells. Control of haematopoiesis is complex The dominant regulator of erythropoiesis is erythropoietin (Epo) produced by the kidney Iron is essential to haemoglobin formation and function Typically the bone marrow only releases mature cells, however in times of increased need, immature cells will be released into the blood stream Hence looking for polychromasia/reticulocytes in cases of anaemia to assess for regeneration And band neutrophils/left shift in inflammation/infection

Answer 455

Others are essentially non-pathogenic under most circumstances Do not confuse with artefacts/mimics – Heinz bodies, etc Anaplasma- A. phagocytophilum – Tick-Borne Fever in ruminants Leukocytes, erythrocytes, platelets Babesia- In cattle in UK – Babesia bovis Erythrocytes Theileria- Not in UK – East Coast Fever in cattle Reproduction by schizogony in lymphocytes (tissue/leukocytic phase) then fission in erythrocytes Ehrlichia- Not in UK? Leukocytes Mycoplasma- Cats Formerly Haemobartonella Erythrocytes The hemolytic anemia caused by M. haemofelis is called Feline Infectious Anemia (FIA) Cytauxzoon- Not UK Cats Ertyrhocytes plus macrophages in tissues Birds- Hemoproteus, Leukocytozoon, Plasmodium

Answer 456

Leishmania- Protozoa Spread by sandfly Amastigote stage found in macrophages Granulomatous dermatitis in cutaneous form Granulomatous splenitis, lymphadenitis and hepatitis in visceral form Histoplasmosis- Fungus Soil-borne Typically seen in the lungs (ddx: Blastomycosis) Will spread to lymph nodes

Answer 457

Typically due to pyogenic bacteria- Acute suppurative lymphadenitis Streptococcus equi ssp. equi (Strangles) Rhodococcus equi Trueperella pyogenes

Answer 458

Typically due to intracellular and/or persistent bacteria Chronic (pyo)granulomatous lymphadenitis Mycobacterium bovis Mycobacterium avium subspecies paratuberculosis- Johne’s Corynebacterium pseudotuberculosis Also parasites and fungi – see previous slide

Answer 459

Puppy strangles

Answer 460

Primary isolated splenitis is generally uncommon in dogs and cats- Often secondary to another disease process, such as peritonitis or neoplasia Or in cattle may see granulomas caused by Mycobacterium bovis in addition to other organs Leishmania and Hepatozoon (not in UK) should be consider as primary causes of splenitis in dogs however often other organs affected In cats consider Tularaemia - Francisella tularensis Zoonotic and potential to be weaponised Not in UK Lymphadenitis also Severe lymphoid depletion in the spleen and thymus is a feature of numerous viral diseases, including rinderpest, canine distemper, equine herpes virus, canine parvoviral enteritis, feline panleukopenia, and bovine viral diarrhoea Necrotizing lymphadenitis, splenitis, and hepatitis in laboratory animals due to various infectious agents: Tyzzer’s disease (Clostridium piliformis): Mice, gerbils, and other laboratory and wild rodents Multifocal foci of hepatic necrosis (older mice), catarrhal enterocolitis with mesenteric lymph node abscesses (younger mice); myocardial lesions occasionally (especially gerbils) Yersiniosis (Yersinia pseudotuberculosis): Cats, Guinea pigs, rabbits, rats, other rodents Acute: Enteritis (ileum) with mucosal ulceration Subacute to chronic: Discrete miliary to caseous lesions in lymph nodes, spleen, liver and lungs Bacteria are easy to visualize, in contrast to F. tularensis Salmonellosis (Salmonella sp.): Guinea pigs, mice, rats, other rodents Acutely--focal areas of necrosis in liver, spleen, and lymphoid tissue and intestine Bubonic plague (Yersinia pestis): Rats, squirrels, and other rodents

Answer 461

Parvoviruses- Replication depends on host-cell DNA polymerases produced in the S phase of the cell cycle. Therefore, has a predilection for cells that are rapidly dividing- Foetal tissues – heart (puppies), cerebellum (kittens), haematopoietic and lymphoid tissues, intestinal crypt epithelium Bovine Viral Diarrhoea Virus (BVDV)- Subclinical infection usually by non-cytopathic BVD followed by seroconversion is the most common form- Transient leukopenia may be seen with onset of signs of disease. Infection of the dam- 50-100 days gestation: Foetal death, abortion, mummification 100-150 days gestation: Congenital brain defects, cataracts microphthalmia Persistent infection is an important sequela of foetal infection with noncytopathic BVDV occurring with infection prior to 125 days gestation- Persistently infected calves may appear healthy and normal in size, or may be stunted and prone to respiratory or enteric infections. Viraemic but do not seroconvert Superinfection of the PI calf with cytopathic form = mucosal disease- Fever, leukopenia, dysenteric diarrhoea, inappetence, dehydration, ulcers of the nares and mouth. Death within a few days of onset. PM -> Erosions and ulcerations throughout the GI tract., mucosa over Peyer’s patches haemorrhagic and necrotic, extensive necrosis of lymphoid tissues Feline immunodeficiency virus (FIV) Three phases of infection - the acute phase, the asymptomatic (or latent) phase, and the progressive phase. Acute phase- generally occurs 1-3 months after infection Replicates in T-cells of within lymph nodes Spreads to other lymph nodes, resulting intransient lymphomegaly and fever Asymptomatic phase- Months to years. Replicates very slowly Cyclical lymphopaenia and/or increased globulins Some cats will remain in this stage and never progress to more severe disease. NEVER euthanise a cat on a snap test alone FIV (Feline Immunodeficiency Virus) (cats.org.uk) Progressive phase- Progressive immuno-compromised state Secondary infections may occur – gingivitis very common Ongogenic (see next slide) Snap test tests for the antibody Feline leukaemia virus (FeLV)- Subgroups A,B,C & T; A, B, and C are most important FeLV-A is the only one that is contagious, found in almost 100% infected cats and is predominately immunosuppressive; FeLV-B and C results from recombination or mutation FeLV-B is found in ~50% of infected cats; commonly associated with neoplastic transformation and lymphoma (see next slide) FeLV-C arises from a mutation of the envelope gene of FeLV-A; it is present in about 1% of infections and is associated with anaemia following bone marrow infection (non-regenerative) Snap test tests for the antigen

Answer 462

Retroviruses Insert copies of their RNA into host DNA Bovine leukaemia virus - Notifiable Avian leukosis Lentiviruses- FIV FeLV Maedi-Visna FIV- The risk for developing lymphoma in FIV-infected cats is fivefold to sixfold higher than in uninfected cats Intestinal B-cell lymphoma FeLV- Lymphoma is increased 60-fold in infected cats Commonly results in T-cell mediastinal/thymic lymphoma Vaccination has markedly reduced this

Answer 463

Congested/bloody- Torsion Barbiturate euthanasia Acute haemolytic crisis African swine fever Septicaemia- Salmonella, Anthrax Non-congested/firm/meaty Neoplasia- Lymphoma, Mast cell tumour (cats) Chronic immune-mediated haemolytic anaemia Chronic infection- Mycoplasma, etc Chronic inflammation

Answer 464

Anthrax is a cause of outbreaks of sudden death, particularly in ruminants, however can affect other grazing animals and humans. Clinical signs in animals that do not die suddenly include high fever, tachycardia and tachypnoea, and congested and terminally cyanotic mucosae with haemorrhage. Animals that survive longer than a day may have dysentery, abortion, oedematous swellings of the perineum, throat and abdominal wall, and blood-stained milk. The characteristic sign in pigs is swelling of the pharyngeal region and neck. Anthrax is notifiable and zoonotic, so if you suspect it you must call APHA Due to the high fever, animals decompose rapidly resulting in typical saw-horse bloated appearance DO NOT open up the animal, it is spread by spores which can become aerosolised If the animal has been accidentally opened up, immediate gross post mortem findings include blood filled cavities and marked splenomegaly Diagnosed in field by taking a blood smear from the ear Rod-shaped bacteria with capsule

Answer 465

Forms and clinical signs- Peracute, acute, subacute, and chronic forms High fever Cutaneous erythema in all forms Dyspnoea, vomiting Chronic form – abortion, lameness, pneumonia, wasting Pathology- Enlarged friable spleen Haemorrhages in lymph nodes, particularly gastrohepatic Petechial haemorrhage in kidneys and peri-renal oedema Tri-cavity effusions Marked pulmonary oedema Gall bladder oedema

Answer 466

Forms and clinical signs- Peracute, acute, subacute, and chronic forms High fever Generalised vasculitis results in haemorrhages, infarction and cyanosis Infarction of ear tips will result in necrosis Chronic form – marked weight loss, poor reproductive performance, abortion or weak tremoring piglets Pathology- Splenic infarctions Haemorrhages in lymph nodes and necrosis of tonsils Chronic - mucosal ulcers at ileocaecal junction, lymphoid atrophy in lymph nodes and thymus

Answer 467

Discrete single or multiple splenic masses are common in the aged dog Bloody versus firm Irrespective of the diagnosis, they will commonly rupture resulting in a haemoabdomen Rarer in cats, where mast cell tumours are the most common splenic tumour and tend to cause diffuse enlargement Benign- Nodular hyperplasia Haemangioma Haematoma Indolent- Marginal zone lymphoma Malignant- Haemangiosarcoma Histiocytic sarcoma

Answer 468

is a pinpoint (1 to 2 mm) haemorrhage that occurs mainly because of diapedesis associated with minor vascular damage

Answer 469

larger than petechia up to 2 to 3 cm in diameter haemorrhage that occurs with more extensive vascular damage

Answer 470

affects larger contiguous areas of tissue than petechia and ecchymosis

Answer 471

Haemorrhage that occurs in a focal, confined space forms a haematoma, most common in the ears of long-eared dogs or pigs and in the spleen after trauma to the vasculature

Answer 472

blood in the peritoneal cavity

Answer 473

blood in the thoracic cavity

Answer 474

blood in the pericardial sac

Answer 475

bulge in an artery due to defect in the wall

Answer 476

Arterial aneurysms and their subsequent ruptures are rare in animals Rupture of the aorta, pulmonary artery and coronary artery has been reported in swine and turkeys fed a diet deficient in copper Dissecting aneurysms in the coronary and renal arteries in young male racing greyhounds, probably due to arteriosclerosis and haemodynamic stress In horses, aortic sinus of Valsalva aneurysms or tears in the aortic root are well‐recognised conditions in breeding stallions, often leading to sudden death. Developmental collagen disorders, such as the Ehlers-Danlos and Marfan syndrome Smaller haemorrhages in vitamin C deficiency (scurvy) in guinea pigs and primates

Answer 477

->small numbers of erythrocytes escape by diapedesis caused by: Endotoxemia- toxins produced by baceria in the gut Infectious agents- canine adenovirus-1, adeno viruses are endothelialtrophic Chemicals- uremic toxins Immune complexes can become entrapped between endothelial cells and activate complement and neutrophil influx to result in damage to the endothelium and vessel wall- Feline infectious peritonitis- why cats get swollen belly. damaged endothelium causes leakage Recap - see glomerulonephritis section in kidney biopsy lecture

Answer 478

haemostasis- stopping bleeding Arteriolar vasoconstriction- Transient Mediated by reflex neurogenic mechanisms Primary haemostasis- Formation of platelet plug Secondary haemostasis- Clotting factors and production of fibrin Thrombus and antithrombotic events (resolution)

Answer 479

Adhesion- vWF (von willebrand factor) is released by local activated endothelium and coats the exposed collagen vWF acts as a bridge between platelet surface receptor and collagen Activation- Caused by thrombin and ADP Results in shape change and release of thromboxane- go from round to flattened to bridge gap further release of prothrombotic agents Aggregation- Glycoprotein IIb/IIIa allows binding of fibrinogen Fibrin (formed by 2ry haemostasis) stabilises

Answer 480

assosiated with chnge in coat colour aleutian mink, cattle, persian cata Congenital disorders of 1ry haemostasis defective storage of ADP

Answer 481

NSAIDs Aspirin inhibits cox Resulting in less thromboxane and thus no platelet aggregation Uraemia Idiopathic immune-mediated thrombocytopaenia- imunne system destroys platlets

Answer 482

The buccal mucosal bleeding time (BMBT) is a test of platelet function. It is indicated in patients suspected of having a primary hemostatic defect despite adequate platelet numbers. Its use and accuracy for the assessment of platelet function are controversial, but it is still widely used in clinical practice for lack of a more accurate or specific test. Method: For a BMBT, the patient is restrained in lateral recumbency and may require light sedation. A strip of gauze is tied around the maxilla to fold up the upper lip sufficiently to cause moderate mucosal engorgement. It is important not to place the gauze too tightly so that blood vessels are not constricted. The BMBT should be performed with a commercial spring-loaded device that creates a small incision of uniform width and depth into the inside of the upper lip. An area devoid of visible blood vessels should be chosen. Any shed blood must be carefully blotted with filter paper, with extreme care taken not to blot the incision itself; doing so may disturb the fragile primary platelet plug (Figure 3). The time taken from incision to cessation of bleeding by first clot formation is recorded (normal = 2–4 minutes in dogs, 1–2.5 minutes in cats).

Answer 483

Coagulation factors are- Plasma proteins, Produced mainly by the liver. Subdivided into : Intrinsic pathway- factors XI and XII Extrinsic pathway- VII both lead into common pathway Common pathway Starts with X Results in formation of thrombin which cleaves fibrinogen to fibrin Vitamin K– dependent factors Span all three parts II, VII, IX, and X

Answer 484

Factor IX deficiency- Haemophilia B: dogs, cats and rarely horses. generally mild in cats and small dogs. more severe in large dogs Factor VIII deficiency- Hemophilia A: dogs, horses, cattle sheep , cats. vleeding can be severe in large dogs and horses Liver disease VitK deficiency- factors II, VII, IX, X warfarin containing/ like rodenticides

Answer 485

Prothrombin Time- Purpose. The prothrombin time (PT), also known as one-stage PT, is the principal test of the extrinsic pathway, but it also tests the common pathway. Because of the short half-life of factor VII, PT is a very sensitive test for early vitamin K deficiency or antagonism (eg, anticoagulant rodenticides). This test result is not affected by the presence of primary hemostatic disorders. Activated Partial Thromboplastin Time- Purpose. The activated partial thromboplastin time (aPTT) tests the intrinsic and common pathways. It is typically prolonged in patients with heritable factor deficiencies (eg, hemophilia A) or hepatic synthetic dysfunction, or in patients with disseminated intravascular coagulation that have consumed clotting factors.

Answer 486

Purpose. The prothrombin time (PT), also known as one-stage PT, is the principal test of the extrinsic pathway, but it also tests the common pathway. Because of the short half-life of factor VII, PT is a very sensitive test for early vitamin K deficiency or antagonism (eg, anticoagulant rodenticides). This test result is not affected by the presence of primary hemostatic disorders.

Answer 487

Purpose. The activated partial thromboplastin time (aPTT) tests the intrinsic and common pathways. It is typically prolonged in patients with heritable factor deficiencies (eg, hemophilia A) or hepatic synthetic dysfunction, or in patients with disseminated intravascular coagulation that have consumed clotting factors.

Answer 488

A thrombus forms antemortem within a vessel

Answer 489

a section of a thrombus that has broken off and lodged elsewhere

Answer 490

An antemortem clot is a coagulum of blood and/or plasma that forms when bleeding into a cavity

Answer 491

are found within vessels and the heart and are a product of blood stasis and clotting post mortem

Answer 492

need one of these three things to form a thrombus Abnormal blood flow- Valvular disease Heart disease Shunts Aneurysms Hypovolaemia Torsions Hypercoagulability- Glomerular disease- Loss of antithrombin 3 Metabolic disease Inflammation Platelet activation- Neoplasia Endothelial injury- Infectious diseases Free-radicals - vit e/selenium deficiency Toxins Trauma severe cases will have all three

Answer 493

Local stasis or reduced flow (e.g., gastric dilation and volvulus, intestinal torsion and volvulus, varicocoele, external compression of vessel) Cardiac disease (e.g., cardiomyopathy, cardiac hypertrophy) Aneurysm (e.g., copper deficiency in pigs, Strongylus vulgaris) Hypovolemia (e.g., shock, diarrhoea, and burns) Normal blood flow is laminar such that the platelets (and other blood cellular elements) flow centrally in the vessel lumen, separated from endothelium by a slower moving layer of plasma.

Answer 494

Anti-thrombin 3- an important anti-coagulant it is a small molecule thus one of the first to be lost with glomerulonephritis Aortic trifurcation thrombosis is an important but relatively uncommon sequel of hyperadrenocorticism in dogs- Pathogenesis not completely understood: Thrombocytosis Decreased antithrombin concentrations secondary to glomerular changes and proteinuria Decreased fibrinolysis Relative increases in the concentrations of circulating procoagulant molecules, such as factor VIII and fibrinogen In humans, 80% of patients with diabetes mellitus die a thrombotic death- The plasma levels of many clotting factors including fibrinogen, factor VII, factor VIII, factor XI, factor XII, kallikrein, and von Willebrand factor are elevated in diabetes DM a potential sequel of HAC

Answer 495

Roles of the endothelial cell- Solute/metabolite diffusion/transport Local vasoconstriction and vasodilation Coagulation Inflammation Wound healing and angiogenesis In normal circumstances the endothelial cells are slightly anti-coagulant, but become pro-coagulant when needed vonWillebrand’s factor plays a crucial role in primary coagulation- Synthesized in endothelial cells (and megakaryocytes) Stored in Weibel-Palade bodies vWF enables adhesion of platelets to subendothelial extracellular matrix

Answer 496

Diffuse or severe endothelial damage and/or platelet activation with or without severe inflammation can result in disseminated intravascular coagulation (DIC) DIC results in widespread consumption of clotting factors and platelets = consumptive coagulopathy The outcome is microthrombi within small vessels which can contribute to multi organ failure (MOD) and widespread haemorrhage

Answer 497

Thrombi can develop anywhere within the CVS Arterial thrombi Venous thrombi- Slower flowing blood so will typically completely occlude vessel and take the form of the vessel Post mortem clotting- Not adherent to the wall of the vessel Separates into cells and plasma = chicken fat clot

Answer 498

An infarct is a local area of very acute (peracute) ischemia (complete lack of oxygen) that undergoes coagulative necrosis. Infarction is caused by the same events that result in ischemia and is most common secondary to thrombosis or thromboembolism. The characteristics of an infarct are variable based on the type and size of vessel that was occluded (artery or vein), the duration of the occlusion, the tissue in which it occurs, and the prior perfusion and vitality of the tissue.

Answer 499

Epistaxis- nose bleed Spontaneous haemorrhage Gastrointestinal bleeding Prolonged bleeding after surgery Excessive menstruation in intact females Ecchymosis, petechiae, bruising

Answer 500

Buccal mucosal bleeding time (BMBT) Mucosal membrane of the lip Standardised cut made in lip, e.g.: 5 x 1 mm End point = bleeding stops & crescent of blood no longer forms on filter paper Normal <4min (dogs) <3mins (cats)

Answer 501

Thrombocytopenia- Consumption, haemorrhage Immune mediated thrombocytopaenia Disseminated intravascular haemolysis (DIC) Decreased platelet function- Rare inherited disorders Platelet function inhibited by uraemia of renal failure Therapy, e.g.: Aspirin Von Willebrand’s Disease- Lack of or reduced amounts of Von Willebrand’s Factor Dobermans

Answer 502

haematology analyser Units: # x10^9/L Counted in the same channel as erythrocytes However platelets are smaller

Answer 503

Platelet clumps- Clotting during sampling In vivo activation Platelets counted as RBCs (and vice versa)- Dogs: Akitas: Small red blood cells CKCS: Macroplatelets Cats, Goats: Small red blood cells

Answer 504

Thrombocytopenia? → ALWAYS CHECK A BLOOD SMEAR! Check for platelet clumps (feathered edge) Manual count Body of the smear count how many platets you can see in each hightly magnified field of view Average of 10 hpf x 15 count how many platets you can see in each hightly magnified field of view over 150-200 is good Check for Macroplatelets May also effect [RBC] lower count of macroplatlets ok

Answer 505

Thrombocytopenia (<10 x10^9/L, normal: >150)- Antibodies bind directly or indirectly to platelets Platelets are destroyed / phagocytosed by macrophages Primary- Idiopathic Most common in dogs IMHA + IMTP = Evan’s Syndrome Secondary- Drugs (e.g.: Sulphonamides in dogs, Methimazole in cats) Infections (e.g.: Ehrlichia, Leishmania) Neoplasia Diagnosis- Spontaneous haemorrhage Thrombocytopenia <10 x10^9/L Confirmed on blood film examination Diagnosis of exclusion Therapy- Immunosuppression: Steroids, Azothioprine with supportive care

Answer 506

DIC- Widespread uncontrolled activation of coagulation cascade Platelets are consumed → thrombocytopenia Clots are dissolved → Excessive fibrinolysis = ↑ D-Dimers must have all 3 FDPs- no comercially availabe Causes- Envenomation Systemic inflammation / infection (e.g.: Septicaemia, vasculitis) Massive necrosis Heat stroke

Answer 507

Measured on citrated plasma Form when cross linked fibrin is cleaved by plasmin Used to assess ↑ fibrinolysis associated with coagulation Clots are dissolved → excessive fibrinolysis = ↑ D-Dimers Causes for high level Localised or disseminated intravascular coagulation (DIC) Sepsis, systemic inflammation, haemorrhage, neoplasia, surgery, immune-mediated disease Decreased hepatic or renal clearance

Answer 508

Angiostrongylus vasorum = Lungworm Becoming more common in the UK Infected by ingestion of slugs and snail (intermediate host) Clinical presentation Coughing / Difficulty breathing Inappetent Vomiting or diarrhoea Weight loss Depression / Lethargy Bleeding: Cutaneous bruising and intra-cavitatory haemorrhage Bleeding pathogenesis: Excessive intravascular coagulation Thrombocytopenia (consumption) Consumption of coagulation factors Diagnosis Broncho-alveolar Lavage (BAL) & Cytology Faecal analysis: Baermann technique PCR: Faeces, blood, BAL ELISA test: Detects antigen Therapy Moxidectin & Imidacloprid, Milbemycin oxime & Praziquantel

Answer 509

Von Willebrand factor (vWF) Exposed when vessel wall is damaged Binds platelets to endothelial wall Von Willebrand Disease Most common hereditary bleeding disease in dogs Doberman most common breed Different types = Reduced concentration or complete absence of vWF Presentation- Mucosal haemorrhage: Epistaxis, GI haemorrhage, prolonged oestrus Prolonged bleeding after surgery Cutaneous bruising Diagnosis- Prolonged buccal mucosal bleeding time Measurement of vWF: <50% = Decreased Genetic test for vWD type I (most common)

Answer 510

Coagulation times’ = APTT and PT- Stimulate the coagulation pathway in vivo The it takes until a clot is detected Activated partial thromboplastin time = APTT Assesses intrinsic + common pathways Prothrombin time = PT Assesses extrinsic + common pathways

Answer 511

Intrinsic + Common factors XII, XI, IX, VIII, X, V, II, I Hereditary- Haemophilia A = deficiency in factor VIII Haemophilia B = deficiency in factor IX Factor XII deficiency = most common in cats, no clinical haemorrhage Acquired- Hepatic disease Vitamin K malabsorption Vitamin K antagonism (rodenticide toxicity) DIC or local consumption of coagulation factors

Answer 512

Extrinsic + Common factors VII, X, V, II, I Hereditary Factor VII - prolonged PT, normal aPTT Affected dogs generally do not have a history of bleeding Bruising / prolonged bleeding following surgery Acquired Hepatic disease Vitamin K malabsorption / antagonism (rodenticide toxicity), this goes up first in this case DIC or local consumption of coagulation factors

Answer 513

Vitamin K dependent factors- Factors II, VII, IX & X These factors require Vitamin K to be functional Malabsorption of Vitamin K- Gastrointestinal disease (e.g. inflammatory bowel disease) Vitamin K antagonism- Rodenticide toxicity (e.g. Warfarin) - dogs Mouldy sweet clover - ruminants, horses, pigs

Answer 514

Very common in dogs Clotting factors II, VII, IX and X affected Diagnosis Visible clinical signs can take 5-7 days to appear after ingestion Monitor clotting times on a daily basis for at least 3 days Prothrombin time (PT) will become prolonged first Therapy Vitamin K1 supplementation Severe cases → plasma / blood transfusions Replaces coagulation factors to allow rapid cessation of haemorrhage

Answer 515

Diagnosis <1% factor VIII activity: reference interval: 50-200% Prolonged APTT only (not PT) All animals Severe in larger dogs, horses & japanese brown cattle X-linked recessive mutation in Factor VIII gene Males are either affected or not (never carriers) Females can be free of the defect, carriers (heterozygous) or rarely affected (homozygous).

Answer 516

Diagnosis <1% factor VIII activity: reference interval: 50-200% Prolonged APTT only (not PT) Dogs & cats Mild in small dogs, severe in large dogs X-linked recessive mutation in Factor VIII gene Males are either affected or not (never carriers) Females can be free of the defect, carriers (heterozygous) or rarely affected (homozygous).

Answer 517

Excessive accumulation of the yellow/orange pigment (bilirubin) in the tissues and blood (hyperbilirubinaemia) Bilirubin is made during the normal process of breaking down red blood cells. Most often seen in the shclera , mm skin

Answer 518

direct breakdown product of haem – in soluble and can only travel in blood stream attached to albumin and unable to excrete directly from the body Uncojudated bilirubin is formed by the breakdown of hemoglobin in the red blood cells. The liver converts this bilirubin into direct bilirubin, which can then be released into the intestine by the gallbladder for elimination. Total bilirubin levels are therefore indicative of both the destruction of red blood cells and the proper functioning of the liver, gallbladder, and bile ducts. This is bound to albumin and is the dominant form of total bilirubin in blood. It is produced in macrophages from breakdown of heme groups (specifically the porphyrin ring of heme). The biggest source of heme is hemoglobin within red blood cells (RBC) Unconjugated bilirubin is then released into plasma where it binds to albumin. Uptake of unconjugated bilirubin occurs in the liver and is carrier-mediated and passive. Once within the hepatocyte mitochondria, unconjugated bilirubin is transported with ligandin (Y protein or glutathione-S-transferase A) or other proteins (e.g. fatty acid binding protein) and the majority is conjugated to glucuronic acid by UDP-glucuronyl transferase (from the UGT1A1 gene). Under physiologic conditions, most of the unconjugated bilirubin in blood comes from normal RBC turnover, where RBCs that have completed their normal lifespan (effete) are removed by macrophages in the spleen, liver and bone marrow. Small amounts of bilirubin also come from other heme-containing proteins, such as myoglobin. As RBCs age, they accumulate oxidative injury, which causes exposure of an antigen on RBCs, which is recognized by macrophage receptors, resulting in phagocytosis (extravascular hemolysis) and conversion of the porphyrin ring of hemoglobin into biliverdin and then unconjugated bilirubin (indirect bilirubin on chemistry panels).Macrophages export the unconjugated bilirubin into blood, where it binds to albumin as it is water insoluble. The albumin-bound unconjugated bilirubin is take up by transporters in the hepatocytes on the sinusoidal (blood or lumen) side of the membrane. The unconjugated bilirubin is transported internally within the hepatocyte by ligandin or Z protein and then conjugated to glucuronic acid (glucose in horses) to form conjugated bilirubin (direct bilirubin on chemistry panels), which is water soluble.

Answer 519

water soluble and can be excreted from the body Conjugation renders bilirubin water soluble. Only very small amounts in blood because it is normally excreted into bile. The conjugated bilirubin is then excreted into the biliary system by transporters on the canalicular or biliary side of the membrane (different from those that take up unconjugated bilirubin from blood) along with bile salts and is either stored in the gall bladder (for those species with a gall bladder) or excreted directly into the small intestine. Within the small intestine, the conjugated bilirubin is degraded by bacterial proteases to urobilinogen, around 10% of which undergoes enterohepatic recirculation after uptake by the portal vein. The “reclaimed” urobilinogen is then freely filtered by the glomerulus and is found in urine (there is a pad for urobilinogen on a urinary dipstick but it is not used in veterinary medicine as a diagnostic test). The rest of the urobilinogen is reduced to stercobilin (either directly or via stercobilinogen), which is excreted in the feces. Stercobilin imparts the brown color to normal feces.The excretion of conjugated bilirubin into bile is the rate-limiting step of the entire pathway of bilirubin metabolism and is ATP- or energy-dependent.

Answer 520

Accelerated red blood cell destruction and increased bilirubin production Immune mediated haemolytic anaemia (IMHA) If this bilirubinemia overwhelms the liver’s functional capacity for uptake, conjugation, and secretion, bilirubin is refluxed from the liver into the circulation resulting in hyperbilirubinemia and icterus.2

Answer 521

Hepatocellular disease- Reduced hepatocyte uptake Reduced Conjugation Reduced secretion of bilirubin intrahepatic cholestasis associated with hepatocellular injury, necrosis, or dysfunction Hyperbilirubinemia that occurs in most diseases of the liver is a mixture of conjugated and unconjugated bilirubin in varying proportions – reflux back into the intravascular system Viruses heptatp toxic drugs

Answer 522

Disruption of bile flow through the extrahepatic biliary system- gall stones, tumours ect often show the most yellowing of the skin

Answer 523

icteric plasma Saline agglutination Coombs test Blood smear

Answer 524

can detect whether the problem is the liver by Liver disease is more common cause of incterus in non=haemytic patients can detect whether the problem is the liver by: The blood test ALT ALP GGT AST however most systemic diseases will affect liver and therefore affact these so instead you can do : BAST= shows liver function Bile acid stimulation test for liver function liver disease include viral or bacterial infections, ingestion of toxic plants or chemicals, certain drugs and medications, cancer, autoimmune diseases, and certain breed-specific liver diseases.

Answer 525

Gall bladder obstruction Extremely icteric Obstruction of the common bile duct is associated with a number of diverse primary conditions, including inflammation (eg, pancreatitis, duodenitis, duodenal foreign body, etc), cholelithiasis, gallbladder mucocele, choledochitis/cholecystitis, neoplasia, bile duct malformations, parasitic infection, extrinsic compression, fibrosis, and bile duct stricture. can see some of these on ultrasound ALP and GGT increase more gallbladder mucocele- looks like kiwi fruit on ultrasound, common in older border terriers

Answer 526

Fluidic- Vasodilation Increased vascular permeability Cellular- Leukocyte recruitment

Answer 527

infections- Bacterial, viral, fungal, parasitic Microbial toxins Different pathogens elicit varied inflammatory response Tissue necrosis - Elicits inflammation by releasing molecules from necrotic cells, regardless of the cause of cell death Ischaemia, trauma, and physical and chemical injury Foreign bodies - May elicit inflammation themselves or because they cause traumatic tissue injury or carry microbes Immune reactions = hypersensitivity - Reactions in which the normal protective immune system damages the individual’s own tissues.

Answer 528

Two key features of fluidic phase of acute inflammation- Vasodilation Increased vascular permeability chemical mediators- preformed mediators on scretory granules- histamine ect newly synthesised mediators made at time of inflamation- cytikines ect from the liver- factor xII, complement activation

Answer 529

Produced by mast cells in the Acute fliudic phase of inflamation Mast cells are normally distributed throughout connective tissue adjacent to blood vessels and lymphatics within the skin and mucosa When exposed to inciting agent and IgE, degranulate to release histamine Histamine is a vasoactive amine-> vasodilation and increased permeability

Answer 530

produced in acute fluidic phase of inflamation Arachidonic acid metabolites include : Prostaglandins Thromboxane AA metabolites, generally in the acute phase, results in vasodilation and platelet aggregation Made from cell membrane phospholipids Formation is inhibited by some well-know anti-inflammatories- Steroids Meloxicam (Cox-inhibitors) Aspirin

Answer 531

produced in fluidic phase of acute inflamation TNF and IL-1 secretion stimulated by: microbial products immune complexes Foreign bodies physical injury others Mainly produced by macrophages and dendritic cells TNF also made by T cells and mast cells IL-1 made by some epithelium

Answer 532

part of the fluidic phase of acute inflamation Dendritic cells are antigen presenting cells Initially inciting the innate (non-specific) immune system- Produce pro-inflammatory cytokines Mature to also activate the adaptive (specific) immune response

Answer 533

TNF and IL 1 are joined by IL-6 IL-6 goes to brain and produces fever fibrinogen tells bone marrow to make wbc tumour necrosis factor slows heart thrombus formation infalamtion and coagulation are intrinscally linked- facotr 12 is key chemical mediator

Answer 534

Coagulation and inflammation are activated by similar insults Key parts of the coagulation cascade, like thrombin and fibrinogen, are also seen with inflammation Thrombin- Cleaves fibrinogen to fibrin -> clot And is proinflammatory as is a monocyte chemoattractant, induces TNF, IL-1 and IL-6 production and mediates leukocyte migration Fibrinogen - Is a glycoprotein synthesized by hepatocytes In pathological conditions, blood concentration of fibrinogen increases= acute phase protein Crucial for scaffolding the haemostatic plug Proinflammatory due to its function of binding and activating leukocytes

Answer 535

Catarrhal/mucoid Serous Fibrinous Suppurative/purulent

Answer 536

Exudation of cell-poor fluid into spaces created by cell injury or into body cavities (effusions) Fluid is not infected & does not contain high numbers of leukocytes. Seen with: Thermal injury to skin - blisters Acute allergic responses - watery eyes/runny nose may not be classified as true exudation

Answer 537

Secretion of thick gelatinous fluid Contains mucus and mucins Occurs most commonly in tissue with abundant goblet cells & mucous glands – runny nose

Answer 538

Characteristic of inflammation of membranes of body cavities and organs- meninges, pericardium, joints Most commonly caused by infectious microbes

Answer 539

Pus = an exudate consisting of neutrophils, the liquefied debris of necrotic cells, and oedema fluid. The most frequent cause = infection with bacteria that cause liquefactive tissue necrosis e.g. Staphylococci - aka pyogenic (pus-producing) bacteria.

Answer 540

Neutrophils are typically the first to arrive- not resident in cells but attracted to inflamation In most forms of acute inflammation neutrophils predominate during the first 6-24hrs- More numerous in the blood than other leukocytes Respond more rapidly to chemokines After entering tissues, neutrophils are short-lived; undergo apoptosis and disappear within 24-48hrs Functions- perform phagocytosis recruit other effector cells Release anti-microbial agents

Answer 541

Inflammation that occurs over a prolonged time and/or fails to resolve. Occurs due to: The acute inflammatory response fails to eliminate the inciting stimulus. After repeated episodes of acute inflammation. In response to specific pathogens.

Answer 542

Resistance to phagocytosis: Fusobacterium necrophorum- Produces leukocidin which is specifically toxic to ruminant neutrophils and reduces phagocytosis by inducing neutrophil apopotosis -> liver abcesses (hepatic necrobacillosis; see image) Persistence after phagocytosis: Due to ability to prevent lysosomal fusion- prevention of fusion of lysosomes containing toxic chemicals within macropahge and hence preventing destruction of pathogen very common in Mycobacteria- e.g TB Isolation: Pyogenic bacteria, Strep/Staph spp., “hide” themselves within lakes of pus Also affects antibiotic penetration; i.e. lancing and flushing cat bite abscesses far better than systemic antibiotics. Unresponsiveness: Certain foreign materials cannot be phagocytosed and/or broken down Plant material, suture materials, silicosis (horses that live on sand), asbestos, atherosclerosis. e.g stick injury Disease of immunity: Autoimmunity- arthrytis Leukocyte defects

Answer 543

1. Quickly sense acute inflammation. 2.Migrate in response to chemotaxins. 3.Remove and kill microbial agents by phagocytosis. 4.Process antigens for presentation to effector cells of the adaptive immune response. 5.Facilitate angiogenesis and remodel the ECM.

Answer 544

Production of myeloperoxidase by neutrophils which themselves also undergo necrosis, resulting in liquefaction and pus Rabbits and birds lack myeloperoxidase, resulting in an inability to form pus Chronically, fibroblasts produce collagen and extracellular matrix proteins to wall off the area = fibrous capsule

Answer 545

occurs when the inciting agent cannot be removed and is largely mediated by macrophages which may become multinucleated or epithelioid Granulomatous inflammation can be : Nodular = (tuberculoid) granulomas Mycobacterium bovis Diffuse = lepromatous Eosinophilic granuloma Mycobacterium leprae

Answer 546

Repair and healing are defined loosely as restoration of tissue architecture and function after an injury Repair (parenchymal and connective tissues) Healing (surface epithelia)

Answer 547

REGENERATION: some tissues are able to replace damaged components and essentially return to a normal state occurs by proliferation of cells that survive the injury and retain the capacity to proliferate In some cases, tissue stem cells may contribute to restoration of damaged tissues (mammals have limited capacity to regenerate damaged tissues/organs) i.e. in the rapidly dividing epithelia of the skin and intestines and in some parenchymal organs, notably the liver. Requires an intact basement membrane CONNECTIVE (FIBROUS) TISSUE DEPOSITION Occurs when injured tissue incapable of complete resolution or if supporting tissue structure is severely damaged May result in scar formation – not normal but provides enough structural stability that the injured tissue is usually able to function Fibrosis: describes the extensive deposition of collagen that occurs in the lungs, liver, kidney, etc. as a consequence of chronic inflammation or in the myocardium after extensive ischemic necrosis (infarction)

Answer 548

some tissues are able to replace damaged components and essentially return to a normal state occurs by proliferation of cells that survive the injury and retain the capacity to proliferate In some cases, tissue stem cells may contribute to restoration of damaged tissues (mammals have limited capacity to regenerate damaged tissues/organs) i.e. in the rapidly dividing epithelia of the skin and intestines and in some parenchymal organs, notably the liver. Requires an intact basement membrane

Answer 549

Occurs when injured tissue incapable of complete resolution or if supporting tissue structure is severely damaged May result in scar formation – not normal but provides enough structural stability that the injured tissue is usually able to function Fibrosis: describes the extensive deposition of collagen that occurs in the lungs, liver, kidney, etc. as a consequence of chronic inflammation or in the myocardium after extensive ischemic necrosis (infarction)

Answer 550

describes the extensive deposition of collagen that occurs in the lungs, liver, kidney, etc. as a consequence of chronic inflammation or in the myocardium after extensive ischemic necrosis (infarction)

Answer 551

Macrophages play a central role in repair by- clearing offending agents and dead tissue, providing growth factors for proliferation of cells secreting cytokines that stimulate fibroblast proliferation and connective tissue development Repair begins within 24 hours after injury with emigration of fibroblasts and induction of fibroblast and endothelial cell proliferation. Angiogenesis (formation of new blood vessels) – supplies nutrients/oxygen for repair; vessels are leaky because VEGF (GF that drives angiogenesis) increases vascular permeability; also due to incomplete interendothelial junctions Formation of granulation tissue – consists mainly of fibroblasts and new capillaries in a loose ECM often admixed with inflammatory cells (mainly macrophages); progressively invades site of injury; amount formed depends on size of tissue deficit and intensity of inflammation Remodelling of connective tissue (produces stable fibrous scar) – process of maturation of the connective tissue. The amount increases gradually leading to reorganisation and formation of a scar.

Answer 552

Angiogenesis is the formation of blood vessels Can occur via- proliferation of endothelial cells from existing blood vessels near the site of injury from bone marrow endothelial precursor cells (EPCs) Hypoxia is the major trigger

Answer 553

glomerulus and Bowman’s capsule

Answer 554

the glomerular capillary hydrostatic pressure.

Answer 555

capillary lumen.

Answer 556

Fenestrated endothelium of glomerular capillaries Glomerular basement membrane Foot processes of the podocytes

Answer 557

Renin- Released by juxtaglomerular apparatus in response to low blood pressure and flow to the kidney Transforms angiotensinogen (made by the liver) to angiotensin I Angiotensin I is converted to angiotensin II by angiotensin-converting enzyme (ACE – made by the lung) Angiotensin II- Acts directly on vessels to result in vasoconstriction-> increase blood pressure Acts on the adrenal gland to produce aldosterone-> kidney tubules resorb salt and water

Answer 558

Released by juxtaglomerular apparatus in response to low blood pressure and flow to the kidney Transforms angiotensinogen (made by the liver) to angiotensin I Angiotensin I is converted to angiotensin II by angiotensin-converting enzyme (ACE – made by the lung)

Answer 559

renin Transforms angiotensinogen (made by the liver) to angiotensin I Angiotensin I is converted to angiotensin II by angiotensin-converting enzyme (ACE – made by the lung) Acts directly on vessels to result in vasoconstriction-> increase blood pressure Acts on the adrenal gland to produce aldosterone-> kidney tubules resorb salt and water

Answer 560

The tubules are responsible for reabsorption of water, glucose electrolytes and bicarbonate The tubules therefore are responsible for urine concentration

Answer 561

Eliminating waste- Urine formation Acid base regulation- Resorption of bicarbonate Conservation of water- ADH/vasopressin Maintenance of electrolyte balance- Potassium, sodium and chloride resorption and excretion Other metabolic and endocrine functions- Production of EPO for haematopoiesis Vitamin D and calcium regulation Maintenance of blood pressure

Answer 562

Directly toxic - aminoglycosides Toxic metabolites – ethylene glycol

Answer 563

Directly toxic - aminoglycosides Toxic metabolites – ethylene glycol

Answer 564

The kidney can cope with low blood pressure and/or reduced renal blood flow to a point, thanks the R-A-A system Sudden acute drops in flow to the kidney or prolonged low blood pressure are less manageable Acute- Sepsis Heatstroke Thromboembolism Acute haemorrhage or shock Chronic- Congestive heart failure Some drugs can directly affect flow to the kidneys- Prostaglandins and COX are involved in the normal maintenance of renal blood flow COX inhibitors such as NSAIDs will thus cause ischaemic necrosis by reducing blood flow via vasconstriction -> Renal medulla/crest necrosis

Answer 565

refers to dilation of the renal pelvis, which fills within urine. Typically due to downstream blockage Increased pressure in the renal pelvis results in no where for urine to go and glomeruli continue to “make” urine -> urine is forced into renal interstitium -> collapse of interstitial vessels -> hypoxia -> repair by fibrosis

Answer 566

Renal failure occurs when one or more of the 5 functions is impaired. The kidney can function appropriately, with little to nothing clinical apparent, with up to 75% of functional mass lost. Acute renal failure can be pre-renal (reduced blood flow), intra-renal (tubular necrosis) and post-renal (urinary obstruction) Results in; Failure to eliminate waste- Azotaemia Inability to maintain acid-base haemostasis- Metabolic acidosis Inability to maintain blood volume and pressure- Hypertension Acutely injured kidneys are generally enlarged- Inflammatory cells Oedema

Answer 567

The systemic changes associated with severe azotaemia Uraemia is a clinical syndrome Whilst in clinical pathology we associate elevated levels of urea and creatinine with renal failure, in reality, over 90 toxins that would otherwise be filtered by the kidney build up in the blood Uraemic toxins damage tissue by- Endothelial damage Also, some of these toxins are leached into saliva and gastric secretions-> metabolised to ammonia -> caustic ulceration of mucosa (tongue, stomach, colon)

Answer 568

When one part of the nephron is damaged, eventually the rest of the nephron follows Replaced by fibrosis Animals with chronic renal failure are azotaemic and will eventually become uraemic Other findings- Hypertension Non-regenerative anaemia Hypokalaemia Calcium deposition in soft tissues

Answer 569

Maintenance of calcium is exceptionally complex Kidneys, gut, bone, thyroid and parathyroid glands involved The role of the kidney is three-fold Resorption of calcium Phosphate excretion Activation of vitamin D Failing kidneys result in Reduced calcium Increased phosphate Inactivated vitamin D- Less calcium absorbed from intestine Chronic renal failure ultimately results in renal secondary hyperparathyroidism Due to low calcium, the parathyroid glands become hyperplastic and produce more parathyroid hormone As there is no other way in the animal of increasing plasma calcium, calcium is resorbed from bone This results in weak bones, replaced by fibrosis = rubber jaw Also the combination of high phosphate and acidosis means calcium is deposited in soft tissues, particularly stomach, kidney and pleura

Answer 570

Aplasia = never formed Hypoplasia = small Dysplasia = abnormally formed Renal dysplasia- Progressive juvenile nephropathies Polycystic kidney disease Heritable- Progressive juvenile nepropathies Typically issue is initially in the glomeruli Due to collagen defect Samoyeds PKD- Persian cats, English Bull Terriers = PKD 1; Autosomal dominant Westies, Cairn terriers, sheep = PKD 2; Autosomal recessive

Answer 571

From within – typically unilateral and singular Renal cell carcinoma Urothelial cell carcinoma From without – typically bilateral and multiple Lymphoma

Answer 572

An under or overproduction of hormones An inability to respond to hormone production. Exogenous hormone administration. Production of hormone-like substances from certain cancers Underproduction of hormones is due to- Immune-mediated destruction of the endocrine organ. Upstream endocrine organ destruction. The inability to produce a hormone due to a nutritional deficiency. Typically, overproduction is due to hyperplasia or neoplasia.

Answer 573

Family: Spirochaetaceae- Leptospira, Borrelia, Treponema Gram-negative-like, slender, motile, flexous bacteria. Helically-shaped / Spiral bacteria. Genomospecies- 64 genomospecies (Pathogenic, intermediate and saprophytic species) 37 pathogenic genomospecies (P1 and P2 subclades) 27 saprophytic subclades Serovars- Based on lipopolysaccharide (LPS) carbohydrate moiety difference Pathogenic leptospiral serovars ~250 Saprophytic leptospiral serovars ~60 Serogroups- Group of antigenically similar serovars

Answer 574

The outer sheath is a multilayered membrane which surrounds the protoplasmic cylinder. Complement evasion, Phagocytosis evasion Adhesion Extracellular matrix binding properties (plasminogen, lamin binding) Iron Uptake, Toxin production Serum resistance, Nutrient importation, Exporting bactericidal and toxic agents

Answer 575

Subclinical Form- Clinically inapparent Responsible for maintenance of infection due to chronic shedding in some cases Peracute Form- Death Short clinical presentation of shock and DIC Acute Form- Fever, vascular injury, haemorrhage, anorexia, shock, signs of renal failure, jaundice, diarrhea, muscle tenderness, reluctance to move and death Acute kidney injury, liver impairment and/or LPHS Chronic Form- Multisystemic failure, chronic hepatitis, chronic interstitial nephritis/renal damage, anterior uveitis Large ruminants Cattle maintain: L. serovar Harjo Incidental infection with Icterohaemorrhagiae, Canicola, Hebdomadis, Sejroe, Pyrogenes, Autumnalis, Australis, Javanica, Tarassovi, and Grippotyphosa serogroups Clinical presentation: Pyrexia, hemolytic anemia, hemoglobinuria, jaundice, drop in milk production, abortion, stillbirth, death Pigs- Maintained serovars: Pomona, Australis, and Tarassovi group Incidental infection: Grippotyphosa, Icterohaemorrhagiae, and Canicola serogroups. Dogs- Fever, vascular injury, haemorrhage, anorexia, shock, signs of renal failure, jaundice, diarrhea, muscle tenderness, reluctance to move and death Maintained serovars: Canicola serovar Incidental infection: Icterohaemorrhagiae serogroup, Grippotyphosa and Pomona (L2 to L4 vaccines) Geographical difference in predominant serovars and L4 vaccines

Answer 576

LEPTOSPIRA – contaminated surfaces, direct contact with infectious agents come into contct with SKIN and MUCOUS MEMBRANE (broken epithelium) Entry and multiplication in blood stream Haematogenous dissemination – bacteraemic phase (leptospiraemia) Dissemination to all the body organs and tissues- Endothelial damage (vasculitis) Resulting vascular damage leads to localized ischaemic necrosis in affected tissues- Acute Febrile Illness Multiorgan Involvement: Tubular necrosis Hepatocellular injury Pulmonary damage Placentitis Myositis Tissue localisation Chronic presentation and Multiorgan Organ failure

Answer 577

Antibody detection- Microscopic agglutination test (MAT) ELISA Point of care assays: Snap Lepto (IDEXX), Witness Lepto (Zoetis) Antigen detection: Bacterial Culture Darkfield Microscopy Molecular Diagnosis and typing: PCR (Real time PCR and conventional PCR), MLST, Gene sequencing Other diagnostic processes include: immunofluorescent antibody (IFA), immunohistochemistry,

Answer 578

Fastidious growth of leptospira in culture- Requires specialized media for isolation and identification Takes about 13 weeks (3months) for confirmation MAT limitations- Subjectivity of interpretation Cumbersome, requires technical expertise, risk of exposure Complex leptospiral taxonomy- Serovar, serogroup and genomospecies confusion Differentiating Infected from Vaccinated Animals (DIVA)- Vaccination confounds serology titre detection Phase of infection and diagnostic detection- Diagnosis best with an idea of the phase of infection Treatment interference with sample quality- Antibiotics administration interferes with PCR and culture

Answer 579

Pale, mottled/petechiated kidney Subcapsular and cortical haemorrhage Enlarged kidney with focal white spotting/necrotic streaks in renal cortex Haemoglobinuric/bilirubinuric nephrosis Chronic renal injury resulting in shrunken or enlarged kidney

Answer 580

Jaundice Haemorrhage (petechial and ecchymotic) Ascites Fibrin thrombi Pleural and pericardial effusion Haemorrhagic gastroenteritis Wet, mottled, heavy and dark red lungs (LPHS) Friable liver

Answer 581

Tubular necrosis- Hypoxia and Ischaemia Accumulation of intratubular haemoglobin and bilirubin Mixed inflammatory interstitial nephritis- Occurs secondary to tubular necrosis Suppurative and lymphoplasmacytic infiltrates Chronic intersitial nephritis- Mononuclear infiltration Interstitial fibrosis due to chronic injury Tubular atrophy Leptospires detection using silver staining

Answer 582

Liver- Coagulative hepatic necrosis Periportal hepatitis (neutrophilic) Intrahepatic bile stasis Muscles- Necrotising neutrophilic myocarditis Myonecrosis and myositis Lungs- Intraalveolar haemorrhage Pneumocyte necrosis Pulmonary oedema

Answer 583

Multifactorial disease process, with common end-point of laminar degeneration Endocrinopathic- Insulin dysregulation (Equine Metabolic Disease) Equine Pituitary Pars Intermedia Dysfunction (PPID) 80% of cases of laminitis have underlying endocrinopathic disorders Inflammatory- Severe infection (sepsis, colitis, endometritis) Traumatic- Excess weight bearing on one limb (contralateral limb laminitis)

Answer 584

(Equine Cushing’s Disease) Age related degenerative condition- Condition of older horses (average age 19yo) Rarely diagnosed in younger horses (<10yo) No sex predilection Ponies more likely to be affected than horses Loss of dopaminergic inhibition Hypothalamus unable to regulate pars intermedia of pituitary gland Hypertrophy / hyperplasia of PI Increase production of many hormones from PI which have wide array of effects on body Functions of cortisol- Increase gluconeogenesis Decrease glucose utilisation Increase glycogen deposition in liver Decrease protein synthesis in muscles Increase fat breakdown and redistribution Decrease production and function of WBCs (immunosuppression) Decrease cell division Clinical Signs Lethargy / Poor performance Coat abnormalities Loss of seasonal haircoat shedding Skeletal muscle atrophy Rounded abdomen Abnormal sweating (↑ or ↓) Polyuria/polydipsia (↑ urinating/drinking) Regional adiposity Absent reproductive cycle/Infertility Laminitis Susceptible to other infections Blood Tests- Basal ACTH assay- Most commonly used test in UK TRH-Stimulation test- 2nd line test for borderline cases

Answer 585

Focus on preventative medicine (PPID cases susceptible to infections)- Regular dentistry Excellent foot care Clipping and supporting thermoregulation Optimising diet and management conditions Diligent parasite control Treatment- Pergolide (Prascend) is drug of choice for PPID Can take time to establish effective dose – close monitoring High doses may be associated with loss of appetite

Answer 586

Clustering of endocrine and metabolic abnormalities associated with the development of laminitis in equidae Obesity or Regional adiposity Insulin Dysregulation Hypertriglyceridaemia Seasonal Hypertension Systemic inflammation Disease of domestication and modern husbandry practices Energy imbalance; calorific excess and under-activity Abnormal feeding patterns & preconception of normal BCS Inappropriate feeding for level of energy expenditure Genetic phenotype for enhanced metabolic efficiency predisposes to obesity Periods of food shortage lead to selection of genes which improve metabolic efficiency Clinical Signs- Laminitis Obesity (general, regional) Resistance to weight loss Lethargy/poor performance Swellings around groin Some EMS cases are not obese Insulin testing- Fasting insulin concentration can confirm hyperinsulinemia where present Post-prandial Insulin- Measure serum insulin 2h after feeding a single dose of glucose (1g/kg) INSULIN DYSREGULATION IS THE UNDERPINNING COMPONENT OF THE MAJORITY OF LAMINITIS CASES

Answer 587

PPID cases can demonstrate a degree of Insulin Dysregulation Cortisol antagonises the actions of insulin Some POMCs released in PPID act as insulin like hormones PPID may only serve to exacerbate pre-existing hyperinsulinaemia Remains an Important consideration / rule-out in horses with Insulin Resistance

Answer 588

chorion yolk sack amnion allantois

Answer 589

points of attachment are diffuse almost all of allantochorin involved (horses, pigs)

Answer 590

1-2 points of contact in a disc shape (rodents)

Answer 591

multiple discrete poitns of attachment(cotelydons) that interact with endometrium (caruncles) to form placentomes (ruminants)

Answer 592

band of tissue forming point of attahcment(dogs and cats)

Answer 593

Cattle: ~ 50% Sheep: ~ 40% Pigs: ~ 60-70% Horses: ~ 60-70% Causes: Maternal and foetal stress Dystocia Appearance- Mummified foetuses Still-birth

Answer 594

Bacteria, viruses, protozoa, fungi- Can affect dam, placenta, foetus or a combination Primarily haematogenous Except in horses where majority of bacterial and fungal abortions are ascending True venereal infections include- Tritrichomonas foetus Campylobacter foetus venerealis Appearance- Mummified or macerated foetus Placental changes

Answer 595

Mostly in multiparous animals (most commonly sows) No bacteria Foetal skin is developed enough to withstand autolysis Absorption of placental and foetal fluids No odour Closed cervix Causes- Genetic twinning (mare) viral (BVD, porcine parvovirus, canine herpesvirus) , protozoan infections (Neospora, ovine toxoplasmosis) placental insufficiencies Further diagnostics on a mummified foetus not possible Usually no effect on subsequent breeding

Answer 596

Foetus is liquified Foetid smell Bones will remain Bacterial cause- Endometritis Open cervix

Answer 597

Associated with- Protracted dystocia Late expulsion of dead foetus Putrefactive ascending bacteria- e.g. clostridial organisms) Foul smell and gas under skin (crepitant) Advanced uterin lesions and dam may die due to toxaemia

Answer 598

Salmonella and other bacterial and fungal contents can be cultured from foetal stomach content Chlamydia and lepto difficult to culture so- MZN stain of foetal stomach content or PCR for chlamydia Foetal kidney PCR for lepto Histopathological +/- IHC of foetal tissues Coxiella also tested for with MZN before proceeding with sheep abortions due to zoonotic risk Brucella testing to maintain Brucella-free testing also MZN Histopathological +/- IHC of foetal tissues- Brain, liver, lung AND PLACENTA Serology – dam blood and foetal fluid

Answer 599

Perinatal mortality may be defined as death of the foetus or perinate before, during or within 48 h of calving at full term (> 260 days in cattle) Includes both stillbirth and early neonatal mortality As well as the previously discussed samples, examination of the foetal thyroid gland for- absolute goitre (thyroid enlarged relative to a criterion-referenced threshold thyroid weight, e.g. > 30 g) or relative goitre (thyroid enlarged relative to a criterion-referenced threshold thyroid g: kg ratio with body weight, e.g. > 0.80) and submission of a fresh (I2 content) and formalinised lobe (histopathology) will detect dietary iodine imbalance. Where selenium deficiency is suspected a fresh sample of the foetal liver preferably or kidneys should be submitted.

Answer 600

elevated or low glucocorticoid response can indicate and animal is not maintianing hoemostasis gcs produced by adrenal gland in response to stimuli facilitate mobilization of ennergy seen in response to mating and agression stimuli can be an indicator of hown individula is coping with stress elevated levels not always bad: increase during breeding, ovulation, pregnancy, partuition and lactation can be natual

Answer 601

synthetic steriod hormones- false pregnancy (progesterone +/- estrogen) GnRH agonists- chemical castration- deslorelin, leuprolide acetate immunocontraception- Vaccine response- PZP, GnRH vaccine

Answer 602

cells within the testes Spermatogonia are the sole proliferative cell population within the seminiferous epithelium and in residing outside of the protective “blood–testis barrier” formed by tight junctions between Sertoli cells. Spermatocytes are the largest germ cells, are mostly tetraploid, and represent the meiotic phase of germ cell differentiation. Spermatids, round and elongating, are the haploid products of meiotic division. With maturation, which involves progressive loss of cytoplasm and organelles, spermatids are dependent on the supporting Sertoli cell for successful terminal differentiation and release. Due to DNA exchange during the process of meiosis, spermatids and spermatozoa become antigenically foreign, and these “immune-privileged” cells (due to their location within the blood–testis barrier) incite an inflammatory response when the seminiferous epithelium is disrupted.

Answer 603

cels within the testes Sertoli cells are large, post-proliferative cells that are essential to spermatogenesis. They serve multiple complex roles, including simultaneous support of synchronous differentiation among several cohorts of germ cells of differing maturity, maintenance of the blood–testis barrier, secretion of seminiferous fluid, release of matured spermatids, and phagocytosis of residual bodies and apoptotic germ cell remnants.

Answer 604

cells within the testes Intratesticular androgen levels, crucial to germ cell maintenance, are sustained by Leydig cells. These endocrine cells are outside of the protective blood–testis barrier.

Answer 605

Mesenchymal tissues can be part of many organs and help to give the organs shape and strength. The basic component of many soft tissues or supporting structures is the substance collagen. Collagen is a protein that is woven from fibrils that give it both strength and resilience (the ability to bend or bounce back). Mesoderm Supporting cells- Fibroblasts -> collagen Endothelia Bone

Answer 606

Epithelial tissues are widespread throughout the body. They form the covering of all body surfaces, line body cavities and hollow organs, and are the major tissue in glands. They perform a variety of functions that include protection, secretion, absorption, excretion, filtration, diffusion, and sensory reception. All endoderm and some ectoderm and mesoderm Cells form bulk of parenchyma of organ, glands or line organs Hepatocytes Skin GIT Bladder Cell-to-cell and cell-to-basement membrane adherence

Answer 607

The establishment of chromosomal/genotypic sex The determination of gonadal sex The development of phenotypic sex

Answer 608

Determined at fertilization – XX or XY zz (male)/zw (female or birds Rarely, aneuploidy (diffretn number of sexchromosomes )can occur resulting in XXX, XXY (Kleinfelter-like syndrome), or X_ (Monosomy X/Turner-like syndrome)

Answer 609

Rarely, aneuploidy (diffretn number of sexchromosomes )can occur resulting in XXX, XXY (Kleinfelter-like syndrome), or X_ (Monosomy X/Turner-like syndrome) male tortushell cats commonly are xxy In the case of cats with Klinefelter syndrome, the extra X chromosome is commonly associated with a failure of the testes to function properly, which explains why male tortoiseshell cats are usually sterile. The partial or complete loss of one X chromosome in humans causes Turner syndrome (TS), which is accompanied by a range of physical and reproductive pathologies. Reported in a pig: Short stature, micrognathia, and skeletal abnormalities in the limbs. Phenotypically female but did not exhibit an estrous cycle, even after reaching the age of sexual maturity, and showed no ovarian endocrine activity. An autopsy at 36 months revealed an undeveloped reproductive tract with ovaries that lacked follicles.

Answer 610

Determined by a variety of genes Primarily involves SRY – which is on Y chromosome and not X chromosome. Female: XX chromosomal sex lacks the SRY and testis-determinating factors WNT4 is important and upregulates folistatin (FST) and DAX1; it also inhibits SOX9 (a male specific gene) FOXL2 and BMP2 also are important in upregulation of FST Wolffian (mesonephric - male) ducts regress in the absence of SRY gene product Outer cortical layer of bipotent gonad becomes ovarian tissue first - ovotestes are usually ovarian tissue on the periphery with varying amounts of testicular tissue in the medulla Male: In the presence of SRY, SOX9 expression is increased, promoting the testicular pathway and blocking the ovarian pathway SRY is also important in early Sertoli cell differentiation

Answer 611

Driven by gonadal factors A functional testis is critical to male phenotypic development Female tubular and external genital development form from paramesonephric (Mullerian) ducts – will develop in the absence of hormones The presence of testosterone and anti-Mullerian hormone (AMH) cause regression of paramesonephric ducts and development of mesonephric (Wolffian) ducts into male genitalia and accessory sex glands AMH is produced by Sertoli cells and testosterone is produced by interstitial (Leydig) cells Ovotestis usually results in varying degrees of masculinization of the tubular and external genitalia – e.g. clitoral hypertrophy, hypospadias

Answer 612

Mesonephric duct cyst A type of paraovarian cyst The mesonephric duct (also known as the Wolffian duct, archinephric duct, Leydig's duct or nephric duct) is a paired organ that forms during the embryonic development of humans and other mammals and gives rise to male reproductive organs. During the early stages, male embryos and female embryos contain the same structures and cannot be differentiated. Paired mesonephric (Wolffian - male) ducts and paired paramesonephric (Müllerian - female) ducts form de novo from longitudinal folds along the lateral inner abdominal wall The uterine tubes, uterine horns, body, cervix, and cranial vagina develop from the paramesonephric duct, The mesonephric tubes become the rete and contribute to the sex cords of the ovary. Normally the ducts of the opposite sex regress; however, their embryonic remnants are frequently encountered in otherwise normal adult animals, appearing as grossly detectable cystic structures in or near the ovary, uterus, cervix, or vagina. Cystic remnants of the mesonephric duct system can sometimes be found in the mesosalpinx, where they may vary in size from a few mm to 20 mm or more. Large cysts can be mistaken for ovaries or ovarian structures during palpation but are generally of no functional significance. Cystic remnants of the mesonephric duct may also be found in the broad ligament of the uterus, where they are also of no consequence, or under the mucosa of the caudal vagina in a ventrolateral position, where they are known as Gartner’s duct cysts.

Answer 613

The mesonephric duct (also known as the Wolffian duct, archinephric duct, Leydig's duct or nephric duct) is a paired organ that forms during the embryonic development of humans and other mammals and gives rise to male reproductive organs. During the early stages, male embryos and female embryos contain the same structures and cannot be differentiated. Paired mesonephric (Wolffian - male) ducts and paired paramesonephric (Müllerian - female) ducts form de novo from longitudinal folds along the lateral inner abdominal wall The uterine tubes, uterine horns, body, cervix, and cranial vagina develop from the paramesonephric duct, The mesonephric tubes become the rete and contribute to the sex cords of the ovary. Normally the ducts of the opposite sex

Answer 614

mesonephric duct paramesonephric duct cyst- on fibrae of fallopean tubes, can be on foals cystic epoophoron

Answer 615

uterine horn hasnt formed properly common in cattle can result in accuulation and infections

Answer 616

Pseudohermaphroditism is a condition in which an individual has matching chromosomal and gonadal tissue (ovary or testis) sex, but mismatching external genitalia. Male pseudohermaphrodite The most common intersex condition XY, SRY +ve Testicular tissue in the abdominal cavity or beneath the skin in the scrotal region, and external genital organs that resemble those of females. Miniature Schnauzers, Basset Hounds, and rarely, Persian cats may present with pseudohermaphroditism when affected by persistent paramesonephric (Müllerian) duct syndrome.

Answer 617

Female internal reproductive organs and typical female karyotype (XX, SRY-ve), but exhibit varying degrees of external physical male genitalia. Most cases of female pseudohermaphroditism result from administration of steroids to pregnant bitches during critical stages of foetal development, inducing virilization of female foetuses can be caused by steroids used on the pregnant mother can also be genetic

Answer 618

Freemartinism syndrome is well known in cattle but has also been described in sheep, goats, and camelids. It causes sterility in females born co-twin to males; ~92% of all heifers born co-twin to bull calves are sterile. These animals exhibit varying degrees of female-to-male sex reversal of the internal and external genitalia. The tubular genital organs in affected animals range from cordlike bands to near-normal uterine horns. Freemartins have a short vagina that ends blindly without communication with the uterus. The cervix is absent. the shared blood supply between the twins will allow the hormaones produced by the male to affect the female

Answer 619

ovarian dysgenesis or ovarian hypoplasia. True agenesis is rare.

Answer 620

Ovarian dysgenesis has been described in several domestic animal species and has been associated with various chromosomal abnormalities (monosomy X or Turner syndrome, trisomy XXX, or Klinefelter syndrome XXY). The ovaries are very small and lack follicular activity. the complete or nearly complete absence of ovarian tissue in phenotypic females.

Answer 621

A wide variety of cysts occur in and around the ovary. Paraovarian cysts are common in the mare Cysts that occur within the ovarian parenchyma include cysts derived from: anovulatory Graafian follicles (luteal and follicular cysts) cystic corpora lutea cystic rete ovarii- The rete ovarii, the homolog of the rete testis, is present in the hilus of all ovaries. cysts of the subsurface epithelial structures Some may interfere with normal reproductive cyclicity, but most are innocuous. Luteal and follicular cysts both are derived from anovulatory Graafian follicles and differ only in the degree of luteinisation Cysts derived from anovulatory Graafian follicles are most common in the cow and sow, but also occur sporadically in the bitch and queen. They often cause altered reproductive activity through secretion of steroid hormones. Affected animals, especially bitches, may show marked manifestations of hyperestrinism, such as altered reproductive behavior, anemia, and hemorrhagic diathesis. In the cow and sow they may be associated with anestrus, persistent estrus, or nymphomania Cystic corpora lutea are essentially a variation of a normal luteal structure and the animal may be pregnant. Cystic rete ovarii- Most common in the guinea pig Cystic subsurface epithelial structures (cystic SES) - Most common in the bitch. The modified peritoneal cells covering the surface of the ovary of the bitch normally extend into the ovary a short distance, where they are arranged as small, single, epithelial lined cavities called “subsurface epithelial structures” or SES. Their importance is 2-fold. They frequently give rise to single, or more commonly, multiple cysts extending along the ovarian surface, and SES often undergo papillary hyperplasia and neoplastic transformation. Neoplasms of the SES are usually adenomas, but carcinomas do occur.

Answer 622

Ovarian cysts are commonly reported in guinea pigs 75.6% in animals >6 years In one paper only arose from rete ovarii but in others from Graffian follicles Rete ovarii should not produce sex hormones, while follicular cysts may be steroidogenic Resulting in typical clinical signs such as bilateral non-pruritic alopecia rule out hyperT and HAC clitoral hypertrophy nipple hyperkeratosis behavioural changes

Answer 623

Follicular and luteal During normal proestrus, regression of the CL coincides with development of a selected follicle, while the growth of any additional follicles is inhibited. In animals developing COD, ovulation fails to occur and the dominant follicle continues to enlarge. Follicular- Frequent, intermittent oestrus Bull-like exaggerated sexual behaviour-, Mounting, Pawing the ground, Bellowing Or sexually quiescence/anoestrous Grossly, follicular cysts resemble enlarged follicles, generally defined as varying in size from 25-60 mm in diameter. Capable of steroidogenesis-products vary from oestrogens to progesterone to androgens. Luteal- Anoestrus Thicker, yellow (luteinized) wall Primarily produce progesterone

Answer 624

Surface epithelium and SES- Papillary and cystic adenomas Papillary adenocarcinomas Sex cord stromal tumours- Granulosa cell tumours Thecoma, luteoma Germ cell tumours- Dysgerminoma Teratoma Gonadal stromal tumours

Answer 625

a germ cell tumour with 2 out of the three cell types- ectoderm, mesoderm, endoderm

Answer 626

In the bitch, the normal oestrous cycle includes differentiation and proliferation of endometrial glands. This is under the influence of oestrogen during proestrus, with more extensive proliferation during oestrus and metestrus/dioestrus under the influence of progesterone. Endometrial hyperplasia is common in domestic canines, often involves cystic distension of endometrial glands (cystic endometrial hyperplasia, CEH). Exogenous sources of progesterone can be found in megestrol acetate, etc. Chronically hyperplastic endometrial glands lead to the gross accumulation of mucoid fluid = mucometra and hydrometra metabolic issue There is debate among authors whether cystic endometrial hyperplasia (CEH) and pyometra are linked, it is currently thought that prolonged exposure to high levels of progesterone cause endometrial gland proliferation which may increase susceptibility of the uterus to infection. E.coli

Answer 627

Metritis in the cow is typically seen post partum - <2weeks assosiated with Dystocia Polymicrobial as opposed to just e.coli in bithces Acute puerperal metritis refers to a severe postpartum uterine infection that results in systemic signs of toxaemia. Clinical metritis is used as a general term for postpartum uterine infections, which may not be associated with systemic signs. Post-partum metritis in sheep and goats is often due to Clostridium tetani and C perfringens

Answer 628

CEM, caused by Taylorella equigenitalis, a microaerophilic gram negative coccobacillus, is a highly contagious venereal disease of mares that is characterized by endometritis, transient infertility, and rarely abortion Stallions do not develop clinical disease, but can transmit the organism; recovered mares can harbour the organism for several months and are an important reservoir Infectious endometritis – similar clinical, gross, and histologic changes; bacteriologic culture to differentiate: Beta-hemolytic streptococci ( equi ssp. zooepidemicus: beta-Strep.) Klebsiella pneumoniae Escherichia coli

Answer 629

Infection of the uterus risks infertility therefore the uterus has many ways to prevent. The vast majority of infections are ascending therefore majority of innate defences focussed on keeping things out, creating a sterile environment for the developing foetus.- Cervix However must also have the ability to allow in antigenically stimulating sperm and be immunotolerant to the foetus. Mucosal immunity- Locally produced IgA, Stops attachment of bacteria to the uterine wall Hormonal changes affecting immunity- Oestrogen stimulates neutrophils, macrophages and T-cells Progesterone down-regulates the immune response

Answer 630

Endometriosis is a chronic disease affecting 5–10% of women of reproductive age Asymptomatic in a minority of the cases, the main symptoms and signs include chronic pelvic pain, dysmenorrhea, pain during intercourse, abnormal uterine bleeding and infertility. Characterized by ectopic endometrial-like tissue (glands and stroma) that induce a chronic inflammatory response, adhesions, and scar tissue. NHPs also develop endometriosis

Answer 631

Uterine endometrial adenocarcinoma The most common neoplasia of the rabbit reproductive tract and probably the most common neoplasia of any body system of female rabbits Carcinoma = malignant 80% will metastasize lungs Leiomyoma/leiomyosarcoma- Tumour of smooth muscle Leiomyomas of genital origin are among the most frequently encountered neoplasms of the female reproductive system in almost all domestic animals, including elephants

Answer 632

Tumour of smooth muscle Leiomyomas of genital origin are among the most frequently encountered neoplasms of the female reproductive system in almost all domestic animals, including elephants

Answer 633

Ascending most common Systemic infections less common but noteworthy are: Mycoplasma Caprine arthritis and encephalitis virus TB

Answer 634

Lactoferrin binds iron which then cannot be utilised by bacteria (bactericidal) Macrophages are the most numerous cell types in normal milk Neutrophil numbers are low unless bacterial infection- Can increase to be the dominant cell type in less than two hours Neutrophils struggle to function in milk Unknown fully why- Can’t swim and phagocytose at the same time? Coated by casein? Are also defective before crossing into the milk from blood in late pregnancy/early parturition- Stress/hormones/nutrition?

Answer 635

Colostrum contains abundant immunoglobulins Protective and transfer of immunity Immunoglobulins also present in milk but less- primary is IgG

Answer 636

Different forms of infectious mastitis occur according to: the aetiology the host response These factors determine the severity of the clinical signs and pathophysiology Severity of mastitis can range from: increased cell counts with no macroscopic changes progressive fibrosis severe toxaemia Diagnosis of the bacteria is important- Obligate mammary pathogen? Staph aureus (most common) Streptococcus agalactiae Mycoplasma sp Environmental? E.coli Both Strep.uberis and dysgalactiae

Answer 637

Gram –ve bacteria Endotoxin production ->Massive cytokine release -> necrosis -> increase in vascular perm Wet gangrene Quarter may slough Sick cow

Answer 638

Gram +ve bacteria- Trueperella pyogenes Strep.dysgalactiae Mycoplasma bovis Dry cows (Summer mastitis)

Answer 639

Contamination of teat-administered drugs are contaminated- Nocardia Cryptococcus Atypical Mycobacteria Candida can be distinguuished form tb as its lwer in the ducts

Answer 640

Caprine arthritis and encephalitis (CAEV)- Retrovirus Indurative mastitis- Hard udder Pathogenesis Not fully understood. Virus-infected macrophages in colostrum and milk are absorbed intact through the gastrointestinal mucosa. Spread throughout the body via infected mononuclear cells. Periodic viral replication and macrophage maturation induce massive lymphoproliferative lesions in target tissues and organs such as the lungs, synovium, choroid plexus, and udder. Persists by residing as provirus within host cells

Answer 641

a rapid proliferation of mammary stroma and duct epithelium of 1 or more glands a non-neoplastic, benign condition that is seen most often in young, intact female cats Cats Young intact females Progesterone

Answer 642

Mammary cancers are common in the dog and cat As a general rule Dog = benign Cat = malignant

Answer 643

the production of one or more calves between 50 and 270 days of gestation; with calves being born dead or surviving for less than 24 hours•All cases where the pregnancy terminates earlyand the foetus is expelled are called abortions. Abortion may be defined as the loss of a foetus between day 42 and 271 of pregnancy, with foetal loss before this stage defined as early embryonic death (before day 14) and late embryonic death (between days 14 and 42). UK law states:•“abortion or premature calving” means an abortion or calving which takes place less than 271 days after service or insemination, or 265 days after implantation or transfer of an embryo, whether the calf is born dead or alive.NB: Not all abortions result in the expulsion of the fetus(es)# Why investigate? •Statutory –Brucella abortus •Economy £630 loss (2007) •Zoonoses •Herd health plan: prevention •‘Sleep at night’ Aims of investigation are: •To determine the cause •To rule out infection(s)

Answer 644

Sporadic abortions are normal: unavoidable losses considered to be between 1.7-2.0% •Ignore twinning? •‘Action level’: increased abortion incidence >3% •Several abortions in short time •Depends on calving pattern •Sick cows, other signs •Feed change or following treatments

Answer 645

•Specific e.g. Brucella abortus•Non-specific e.g. Escherichia coli

Answer 646

•Drug-induced (prostaglandin, corticosteroid) •Insemination/intra-uterineinfusion •Trauma/stress (transport, noise, veterinary treatment etc.) •High fever andendotoxins(toxic plants, nitrate/nitrite, fungal toxins, other disease) •Nutritional (malnutrition, vitamin A deficiency,selenium/vitamin E deficiency, goitre/hypothyroidism- more imortant for still births, wont abort till very end of pregnancy) •Twin pregnancy •Genetic (malformation)

Answer 647

Placenta- •Chorioallantois not amnion •Size and number of cotyledons (range 72-125) •Freshness: smell, colour, texture •Cotyledons: red, pale, necrotic, exudate; fibrin/pus •Intercotyledonaryareas:thickened/’plaques’, exudate; fibrin/pus Aborted calf- •Freshness: smell, colour of viscera (all similar after 24-48hr death in utero) •Size, weight, crown rump length, features of development •Skin lesions, covered with exudate, meconium •Excess fluid in body cavities: clear, pink, red, fibrin •Stomach content:meconium- means calf has been stressed Visceral lesions- •Lungs –inflated (pink, spongey) or not (atelectic; dark pink/red) •Liver –haemorrhages, multifocal lesions, abnormal size/shape/structures •Intestine –atresia (colon, rectum, etc), inflammation/necrosis •Kidney –number, structure •Heart–size, shape, anatomy •Musculoskeletal and others–‘describe what you see’ Brain- •Size and structure, abnormalities? •Cavitation of cerebral hemispheres: hydranencephaly, porencephaly •Cerebellar hypoplasia

Answer 648

Aborted calf (if suitable) •Placenta •Maternal blood? •Bulk milk? •Cohort bloods? •Faeces, environmental samples, etc? Calf samples •Fresh- •Stomach content -Bacteriology, fungal examination(liver or lung if unavailable): •Spleen or thymus-PCR pestivirus •Kidney- PCR Leptospires •Foetal fluid- PCR Leptospires(Antibody tests) •Brain- PCR Neospora •Thyroid (stillborn)- Weigh, iodine adrenal or liver- PCR BoHV-1 Fixed- •Lung, brain, liver, heart, + stomach wall, eyelid- Histopathology Placental samples- •Fixed and fresh cotyledon- Modified ZiehlNeelsen: Coxiella(q-fever),Chlamydia, (+PCR), fungal examination, histopathology

Answer 649

Brucella abortus primarily in cattle Brucella melitensis and Brucella suis infections are possible Clinical signs: Abortions usually 5 to 9 months gestation Retained Foetal membranes and endometritis Orchitis and epididymitis in bulls Hygroma- fluid-filled swelling surrounded by a thick capsule of fibrous tissue that develops under the skin UK history Last outbreak: Cornwall 2004Suckler herd Zoonotic risk: Brucellaspecies are highly infectious to humans:➢raw milk➢infected animals and carcases/placentae Asymptomatic infection in young animals and non pregnant femalesAcute infections: organism in most LNs Even in absence of abortion profuse B. abortus discharge from placenta, fetal tissues/fluids and uterine/vaginal exudateMammary gland and LNs may be infected, excretion in milk Chronic infection also occurs:➢usually do not abort➢excrete in milk and from uterus sInfertility in male and female

Answer 650

•Brucella culture (Farrell’s) on all aborted and stillborn fetuses/placentae or samples- •Milk, mammary gland, reproductive organs*- *if infection/disease suspected •MZN examination: presumptive identification•Specific culture and PCR confirmation Serology- •RBPT- Rose Bengal plate test •CFT-omplement fixation test •ELISA

Answer 651

zoonotic- SalmonellaDublinother Salmonellae: S. Typhimurium, S. Mbandaka, S. MontevideoListeria monocytogenes Coxiella burnetiiChlamydia abortusLeptospirosis nonzoonotic- Bacillus licheniformis Fungi: Aspergillus fumigatus, Mucor, Absidia, etc Trueperella pyogenes Pasteurella, Mannheimia, HistophilussppCampylobacter species

Answer 652

Member of the Enterobacteriaceae Gram negative bacillus, Modified ZiehlNeelson (MZN) positive Several manifestations of disease: ➢Abortion ➢Enteritis ➢Pneumonia ➢Septicaemia ➢Joint ill (polyarthritis) ➢Meningitis/encephalitis ➢Osteomyelitis- proximal thoratic vertebrae ➢Gangrene of extremities (feet, tail, ears)- calves Also causes chronic infection (carriers) Spread by movement of animals and faeces(PVS, farmers, etc)

Answer 653

Soil/environmental- gets into silage Gram positive coccobacillus Survives in reduced pH (to around pH 5.5) Associated with ‘spoilt silage’: soil, poor anaerobiosis Abortion, meningoencephalitis, septicaemia, eye infections May see fine necrotic foci in the liver (‘miliaryhepatitis’)

Answer 654

Gram positive spore-forming bacillus Silage associated including liquor Gross placentitis- leathery change- no cotelydons visible

Answer 655

Silage and another feeds contaminant Gross placentitis+fetal dermatitis- ring worm

Answer 656

Campylobacter fetus venerealis Campylobacter fetus venerealis intermedius- Venereal disease Carried asymptomatically by bull or cows Infertility, EED, abortions Control by stopping natural service (+vaccination) Campylobacter fetus fetus- Opportunistic sporadic abortions Campylobacter jenuni, Campylobacter coli

Answer 657

Gram negative, pleomorphic, obligate intracellular bacterium Carried asymptomatically in some cattle, sheep, goat sZoonotic: in humans causes ‘Q fever’ Modified ZiehlNeelsonstains (placenta preferably), PCR Greatest risk to humans is ‘dust’ from bedding- dapen down bedding, dont spread on windy days

Answer 658

Leptospira hardjobovis Carried asymptomatically in kidneys of cows Passed in urine Zoonotic Abortion, EED, stillbirths, perinatal mortality, infertility Milk drop syndrome ‘flabby bag’

Answer 659

Foot and mouth disease virus Bluetongue virus Bovine viral diarrhoea virus Bovine herpesvirus-1 (BoHV-1 )Schmallenberg virus Neospora caninum Tritrichomonas fetus Sarcocystis species? Anaplasma phagocytophila: ‘Tick borne fever’

Answer 660

found via PCR: brain stem •Histopathology: ➢Brain ➢Heart ➢Liver non suprative inflamation- necrosis •Not all PCR positives abort •Dam serology •Cohort and sibling bleeds

Answer 661

Recognised pathogens: •S. Dublin •L. monocytogenes Opportunists:•pure culture •histopathology

Answer 662

Intracellular bacteria (MZN+)

Answer 663

•BVDv •Neosporacaninum •L. hardjo

Answer 664

Diagnostic rate for infectious causes around 53% •Sporadic abortions are unavoidable •Consider investigating when:•abortion incidence >2% •several abortions in short time •sick ewes, other signs •management changes •treatments all sheep abortions will be screened for brucella

Answer 665

zoonotic- chlamydia abortus toxoplasma gondii campylobacter salmonella listeria •Yersiniaspp.• Other bacteria in pure culture •Pestivirus •Schmallenberg

Answer 666

•Placenta usually required for EAE examination/diagnosis •Also placenta best for toxoplasmosis •May see lesions in lambs –liver, lung, brain Sample collectionTests- •Placenta to include cotyledons-MZN stains, PCR (Coxiella), PCR Toxo •Stomach content-Bacteriology •Body fluid- Toxoantibody (if no placenta) •Spleen/thymus-Pestivirus Follow-up investigations •Fixed viscera, brain, placenta •Ewes •Blood samples

Answer 667

•Poor nutrition/BCS •Pregnancy toxaemia •Rough handling •Transport •Vaccination, foot trimming •Dog worry •Fluke •Worms •Other diseases

Answer 668

Chlamydia abortus (Enzootic abortion)- abortions in last 3 weeks of pregnancy Toxoplasmosis- can effect at any time, blame for bad scanning Campylobacter

Answer 669

Bought-in carrier sheep •Severe placental damage •Late pregnancy abortions (last 3 weeks) •Weak lambs at term •Infection from previous season: abort the next •Same season infection: IP 6 weeks •Damage limitation: long acting tetracycline Pathology- •Inflamed cotyledons/ intercotyledonary •Thick necrotic exudate Testing- •MZ Nonplacental smears •or stomach content if no placenta •Dam serology useful on flock basis

Answer 670

•Cat is definitive host -oocysts (up to 100 million) in cat faeces, can contaminate grazing, hay, straw, cereals, concentrates, silage •10 oocysts infectious dose •Losses at all stages of pregnancy including EED, abortions, mummies, weak full-term lambs Pathology- •Inflamed cotyledons with multifocal necrotic foci → totally necrotic cotyledons- strabery apearence •Little/no intercotyledonaryreaction •Non specificfoetalpathology •Fresh →mummies Testing- •PCR on cotyledon •Antibody detection (IFAT) on body fluid (if no placenta) •(Brainhistopathology) Dam serology useful on flock basis

Answer 671

campylobacter fetus fetus •Campylobacter coli/jejuni •Intestinal carriage by sheep: passed in faeces, vaginal discharges (rapid spread) •Also wild birds, rodents, cattle •Risks: ground feeding, feeding roots, poor trough hygiene •Mix sheep prior to pregnancy- non pregnant sheep get immunity •Imported vaccine Losses at all stages of pregnancy, including weak full-term lambs Pathology- •Lambs: non specific → multifocal hepatitis •Placenta –pale/small necrotic cotyledons Testing •Bacteriology on stomach content •or liver/lungifabsent •NB It takes 4 daysfor initial bacterial ID

Answer 672

Overnight culture usually •Salmonellae •Listeria spp. •Pure culture for opportunistsSalmonellae: S. Montevideo, S. Typhimurium, S. Dublin, many othersListeriaspp.:L. monocytogenes, L. ivanovii

Answer 673

Titres to EAE and T. gondiipeak soon after abortion and decline slowly •ToxoLAT > 64 positive: > 512 high titre •EAE ELISA less easy to interpret •Titres may be present in subsequent season: likely boosted by re-exposure •Negative titres do not rule out infection: problem with screening animals •Vaccinal titres low and decline after 3-4 months •Useful for animals with low scanning % •Not useful in single animals Others- •Border disease •Leptospira hardjo •Coxiella burnetii

Answer 674

Infectious causes compare with those of sheep Tests similar but •There is no foetal antibody test for Toxoplasma gondiiso can only test placenta •Serology comparable but ELISA not validated (use CFT) •Large herd outbreaks of Q fever in Holland resulted in significant human disease in late 2000s

Answer 675

•Isolate aborting animals: minimum of 3 weeks, risk from discharges •Remove and dispose of aborted material: highly infectious •Tetracyclines for EAE are only damage limitation, ewes remain infected •Zoonotic care: several abortifacients are infectious for people, particular risk for pregnant women

Answer 676

cause of foetal loss More commonly causes death of puppies <2weeks old. Herpes virus is latent in the bitch causing no to minimal clinical signs but recrudesces during late pregnancy. Some adults will have ocular and/or vaginal discharge. Puppies are infected during birth. Viraemia as virus spread via macrophages. Incubation period 6-10 days. Puppies are anorexic, hypothermic, vocal, disorientated. Fading puppies? Most if not all of litter will die. Optimum temperature for replication of the virus is 34-36c, hence (partly) why neonates are worse affected, and active warming can improve prognosis. Gross lesions include bilateral, multifocal, petechial and ecchymotic haemorrhages of the kidneys and liver. Necrosis in kidneys, liver and lungs. Typical intranuclear viral inclusion bodies. Virus, like a lot of herpesviruses, is endotheliotropic so most lesions are typically due to death of endothelial cells resulting in damage to blood vessels. Herpes virus is not a core vaccine, but can be given to breeding bitches at request BEFORE and during pregnancy.

Answer 677

cause of foetal loss Zoonotic Transmitted primarily through mating to the bitch then to puppies in utero and milk. Abortion mid pregnancy due to placentitis and endometritis, and aborted material source of infection. Female may continue to shed bacteria intermittently for weeks to months. Aborted foetuses may have renal haemorrhages but bronchopneumonia most typical. If mated again, subsequent pregnancies may reach full term but neonates may be weak or die. In the male, it causes infertility and epididymitis. Dogs with no clinical signs can still be infectious. Discospondylitis common clinical presentation. Testing methods include bacterial culture of any fluid from an adult/foetus and some practices are now offering serology for any imported animal prior to surgery.

Answer 678

cause pof foetal loss Parvovirus Faeco-oral spread Requires infection of rapidly dividing cells to replicate: GIT Bone marrow Early in utero infection: Foetal death and resorption Perinatal infection- 2 wks prenatal - 2 wks postnatal Infection of cerebellum at crucial developmental period- cerebellar hypoplasia -> ataxia 2-4 months postnatal- Infection of bone marrow, thymus, GIT and mucosal lymphoid tissue Leukopenia and enteritis 4-12months - Enteritis

Answer 679

feline panleukopenia virus Feline alpha-herpes virus Feline leukaemia virus Feline infectious peritonitis virus Coxiella burnetti Salmonella spp

Answer 680

herpes virus Brucella canis Salmonella spp. Campylobacter jejuni Strep. canis Leptospirosis spp. Toxosporosis gondii Neospora caninum Leishmania infantum

Answer 681

Screen for contagious diseases to prevent spread •Equid Herpesvirus-1 (EHV-1) •Equine Arteritis Virus (EAV) (Taylorellaequigenitalis(CEMO) –rarely causes abortion) most causes sporadic some cause abortion at specific gestational ages evh1 needs to be rulled out identified by pcr- takes only 1 day

Answer 682

•Measure crown-rump length (CRL) •Weight •Jaundice? •Meconium staining? •Haemorrhage? •Congenital abnormalities •Carcase condition •Carcase preservation

Answer 683

thymus, lung, liver, spleen (kidney- in one container 4 small pieces of chorioallentois in another container

Answer 684

Liver(or heart blood if liver too soft)•Lung (or stomach content)•Chorioallantois

Answer 685

Examine internal organs and sample (our protocol): •Liver–4 small samples ~1-2 cm cubed •Lungs–4 small samples from different lobes •Spleen •Adrenal gland •Kidney–wedge from centre of each kidney (cortex to pelvis) •Thymus •Conjunctiva •Thyroid •Heart •Chorioallantois –5 sample •Amnion –2 samples •Umbilical cord –2 cm section •Any abnormal findings should be sampled examine gut for myconium

Answer 686

Amnion (allantoamnion)- •Cut amnion away from umbilical cord and cut open to lay out flat •Weigh •Examine •2 samples –over blood vessels amniotic plauques- incidental Umbilical cord-Measure length, circumference, weight could see- cord compromise and torsion with haemorrhage and oedema of cord Chorioallantois- Weigh, examine allantoic side and chorionic side. allantoic vesicles- oedema normal unruptured cervical scar avillous area over blood vessels- incidental

Answer 687

•Predominantly bacterial•Fungal uncommon in UK thickened leathery aperence of placenta

Answer 688

Markedly increased clear yellow fluid, thorax and pericardium •Jaundice Thymic necrosis – •colourchange from pink to cream-tan •liquefaction mutifocal hepatic necrosis Jaundice •Pulmonary consolidation •Intranuclear inclusion bodies in hepatocytes EHV-4- ▪Usually sporadic cases ▪Usually have excess of body fluids ▪Liver / lung lesions –sparse or absent ▪Spleen –best site for virus isolation ▪Many lesions secondary to hypoxia (alive foals may survive)

Answer 689

a life-threatening pancytopenia.

Answer 690

Infertility Abdominal distension Weight loss Poor body condition Vaginal discharge Non specific (anorexia, lethargy) Pain (bruxism – pain scoring recommended) Other signs, e.g., GI ileus/stasis

Answer 691

Development of masses Swollen glands Discharge Pyrexia Non specific

Answer 692

Change in testicular shape and texture Change in libido Inflammation/papules/ulcers

Answer 693

Diseases not related to reproductive system- Urinary tract disease Normal urine pigmentation– porphyrin, food pigments Ascites (for abdominal distension) Ovarian disease- Abscesses Cysts Neoplasia Uterine disease- Neoplasia- Uterine adenocarcinoma (rabbits) Polyps Infection Pyometra, metritis, endometritis Hydrometra Endometrial hyperplasia Torsion Endometrial aneurysms Vaginal and vulval disease- Congenital Neoplasia Prolapse Vulvitis-Treponema cuniculi Other- (Pregnancy) Dystocia Pseudopregnancy Pregnancy toxaemia Mammary gland disease- Neoplasia Mastitis

Answer 694

Testicular neoplasia Cryptorchidism Orchitis Epididymitis Prostatic cysts (male neutered ferrets) Preputial/testicular trauma (rabbits) Treponema paraluis cuniculi.

Answer 695

Similar diagnostic testing methods used for dogs and cats. Blood work to assess overall health. Ferrets > oestrogen induced anaemia> collect from saphenous or cephalic vein. Oestrogen induced anaemia >thrombocytopenia, leukopenia & anaemia. Uterine infection > heterophilia with a slight leucocytosis Radiography- Abdominal and thoracic radiography Thoracic > pulmonary metastases Abdominal > mass associated with reproductive tract Ultrasonography- ? Free abdominal fluid Pregnancy Solid mass, versus cysts or fluid filled uterus Ultrasound guided FNA Advanced imaging- CT +/- contrast Cytology Culture and sensitivity Histopathology

Answer 696

Normal pregnancy – need to know normal- Extrauterine pregnancy Dystocia Pseudopregnancy Pregnancy toxaemia Uterine disorders- Pyometra- Purulent vaginal discharge Lethargy Inappetent Enlarged uterus palpable, ultrasonography, cytology, haematology, serum biochemistry Mucometra- Build up of mucus within uterine lumen Hydrometra- Build up of transudate fluid in the uterus Weight gain, but decline in body condition, anorexia, respiratory compromise, abdominal enlargement Clinical signs, ultrasonography Neoplasia- Uterine adenocarcinoma Most common tumour in female entire rabbits Serosanguinous vaginal discharge or haematuria Nonspecific signs > anorexia, depression Dyspnoea if pulmonary metastasis Diagnosis >palpation, radiography (chest as well), ultrasonography, histopathology Often multicentric and involve both horns of the uterus Metastasis via local spread into the peritoneum and other abdominal organs  liver Metastasis via haematogenous route  lungs, brain, skin or bones Cystic mammary glands may be seen in association with this Mammary gland disease- Mammary masses- Progression from cystic mastitis Development of irregular sized, fluctuant, subcutaneous nodules Discharge – milk or amber fluid Clinical signs, FNA and cytology Mastitis- Lactating or pseudopregnant does Common isolates Staphylococcus aureus Pasteurella spp. Streptococcus spp. Hot, swollen, firm, painful glands Pyrexia Depression Clinical signs, culture and sensitivity.

Answer 697

Gestation = 30-32 days Often can gently palpate olive-sized masses from day 10 Fetuses can be seen on ultrasound from day 12 Fetuses difficult to feel abdominally from day 14 Parturition often day 30-32 – usually in the morning and quick Fetuses will not survive after day 35

Answer 698

Testicular tumour- Seminomas, interstitial cell tumours, Sertoli cell tumours, lymphoma Non-painful, firm, nodular testicular enlargement Cryptorchidism- Normally descend by 12 weeks Scrotal sac does not develop on the side of the cryptorchid testicle Orchitis and epididymitis Bacteria > Pasteurella multocida Viral > Myxomatosis Trauma Swollen testes/scrotum, depression, anorexia Trauma-Bite wounds, testicular evisceration and secondary infection Venereal spirochetosis- Treponema paraluis cuniculi Redness, oedema, vesicles, ulcers, scabs around perineum and genitalia (+ face) Clinical signs, microscopic visualisation, silver stains on biopsy, serological testing

Answer 699

Seasonally polyoestrus. Jills remain in oestrus until they are mated, or chemically brought out of oestrus, or the day length shortens. Pro-oestrus indicated by increase in vulva swelling. Oestrus follows – will see large, swollen vulva & behavioural changes. Prolonged oestrus = increases risk of persistent hyperoestrogenism >development of pancytopenia due to bone marrow suppression. Induced/reflex ovulators- Mating a rough process Gestation 42 days Litter size 6-8 Persistent oestrus > pancytopenia Subcutaneous and mucosal petechiae Ecchymoses Swollen vulva Pale mucous membranes Abdominal distension Blood from cephalic vein Poor prognosis

Answer 700

Persistent oestrus > pancytopenia- Subcutaneous and mucosal petechiae Ecchymoses Swollen vulva Pale mucous membranes Abdominal distension Blood from cephalic vein Poor prognosis Pyometra > ascending infection Poor hygiene/husbandry Aggressive hob behaviour Mastitis- After whelping or after third week of feeding Inguinal glands commonly affected first Susceptible to pseudopregnancy > implantation failure due to effects of photoperiod or lack of conception. Associated with HCG injection or mated with a vasectomised hob CS – weight gain, mammary enlargement & nesting behaviour. Pseudopregnant jills may develop a fuller hair coat. After the ‘whelping’ date > jill will cycle back to normal adrenal disease-Correlation with surgical neutering Increase in concentrations of gonadotrophins loss of negative feedback > stimulation of adrenal cortex >adrenocortical hyperplasia and tumour formation CS > symmetrical alopecia, ‘rat tail’, pruritis Vulva swelling Recurrence of sexual behaviour Urinary incontinence > prostatic enlargement

Answer 701

High incidence of ovarian disease- Ovarian cysts Neoplasia Clinical signs: abdominal distension, bilateral alopecia, weight loss, decrease appetite, respiratory effort. Diagnosis: clinical signs, imaging

Answer 702

Pyometra (hamsters & gerbils) Care not to misinterpret in hamsters Diagnosis: clinical signs, ultrasonography, cytology

Answer 703

Neoplasia (mammary tumours) Rats - subcutaneous fibroadenoma Oestrogen and prolactin are thought to playa role in tumour development. ? Early neutering as a preventative measure

Answer 704

Primary reproductive disease is rare. In males, fur ring occurs around the base of the penis Can cause paraphimosis and balanoposthitis (inflammation of the prepuce and glans penis) Clinical signs = excessive grooming of the area, lethargy, straining to urinate.

Answer 705

Clinical signs > haemorrhagic vaginal discharge or haematuria Differentials Uterine neoplasia- Adenosarcoma Endometrial stromal sarcoma Adenoleiomyosarcoma Spindle cell tumour Adenoleiomyoma Endometrial polyps Endometrial venous aneurysms Diagnosis- Clinical exam (abdominal mass) Radiography

Answer 706

A common laboratory method that uses two dyes called hematoxylin and eosin that make it easier to see different parts of the cell under a microscope. Hematoxylin shows the ribosomes, chromatin (genetic material) within the nucleus, and other structures as a deep blue-purple color. Eosin shows the cytoplasm, collagen, connective tissue, and other structures that surround and support the cell as an orange-pink-red color. H and E staining helps identify different types of cells and tissues and provides important information about the pattern, shape, and structure of cells in a tissue sample.

Answer 707

similar to development of cysts in female- incidental finsings

Answer 708

most commonly manifested as an absence of parts of the epididymis

Answer 709

Anomalous/congenital condition failure of the urogenital groove to close in the male birth defect in boys in which the opening of the urethra is not located at the tip of the penis.

Answer 710

Interstitial/Leydig cell tumour Seminoma Sertoli cell tumour

Answer 711

Vascular hamartoma, haemangioma and haemangiosarcoma Melanoma Mast cell tumour

Answer 712

Grossly: The tumours are white Irregularly ovoid Lobulated Bulge when cut May be cystic Abundant fibrous stroma makes then firm to hard May cause marked distortion of the testicle Most are benign The incidence of Sertoli cell tumours is 20 times higher in cryptorchid dogs Up to 30% of affected dogs produce excessive oestrogen, resulting in: Feminization, including attraction of male dogs Reduced libido Testicular and penile atrophy Preputial swelling Perineal hernia Gynecomastia Redistribution of fat Symmetrical, often ventral, alopecia. Squamous metaplasia of the prostate gland (see later slide) Oestrogenic depression of bone marrow can result in; Anaemia Thrombocytopenia Granulocytopenia

Answer 713

The deferent duct is long and seminal fluid is constantly being produced, effectively flushing the tubular genitalia and hindering ascending infection. Seminal fluid contains various antimicrobial products: Chlorine Blood-testis barrier- Barrier between testicular interstitium and germ cells Formed by intercellular junctions of Sertolli cells Innate and acquired immune function is actively suppressed in testicular parenchyma, as spermatocytes, spermatids, and spermatozoa are highly antigenic and outside the blood-testis barrier Innate and acquired immune function is actively suppressed in testicular parenchyma, as spermatocytes, spermatids, and spermatozoa are highly antigenic and outside the blood-testis barrier- Any defect, injury or infection, that results in leakage of spermatozoa or spermatozoal antigens into the extra tubular compartment incites a foreign body or granulomatous response, fibrosis, continued disruption of tubules, sperm

Answer 714

Sheep- Brucella ovis Orchitis: Sheep/Goat pox virus, Visna/maedi virus, Trueperella pyogenes, Corynebacterium pseudotuberculosis, Brucella melitensis, Histophilus ovis Epididmytis: Actinobacillus seminis (most important); Histophilus somni, Mannheimia haemolytica, E.coli, Trueperella pyogenes Pigs- Brucella suis Cattle Brucella abortus Orchitis: Mycobacterium bovis, M. tuberculosis, E. coli, Proteus vulgaris, Corynebacterium ovis, Streptococcus , Staphylococcus sp., Trueperella pyogenes, Actinobacillus spp, Nocardia farcinica, Chlamydia spp,, and Mycoplasma sp Epididymitis: bovine herpesvirus 4 (cytomegalovirus), Actinobacillus seminis, Mycoplasma bovigenitalium, Trypanosoma brucei Dogs Brucella canis- imported dogs Cats Naturally resistant to Brucella Orchitis: FIP Epididymitis is rare Brucella is NECROTIZING

Answer 715

scrotal mange in SHEEP Scrotal inflammation- can reduce fertility

Answer 716

Typically ascending E.coli common Abscessation and sepsis

Answer 717

Benign prostatic hyperplasia is the most common disorder of the prostate in intact males Under the influence of testosterone the prostate will become hyperplastic Is symmetrical May not cause issue but is palpable on rectal exam Clinical signs include haematuria and preputial discharge May be cystic Resolves post castration

Answer 718

Metaplasia is the change from one differentiated cell type to another of the same germ layer. In this case is from cuboidal epithelium in gland formation to stratified squamous In the normal animal the change from specialised epithelia to strat. squamous is protective In the case of prostatic squamous metaplasia, it is due to excess oestrogen via unknown pathogenesis The excess oestrogen in this case would be from a Sertoli cell tumour

Answer 719

Carcinoma as epithelial and typically malignant In the dog, arise more commonly from the urothelial tissue in the urethra= urothelial cell carcinoma (transitional cell carcinoma)- Less commonly arise from the glandular parenchyma= prostatic adenocarcinoma - more common in humans and a mouse model

Answer 720

inflammation of the prepuce

Answer 721

inflammation of the glans penis

Answer 722

inflammation of the entire penis

Answer 723

inflammation of both penis and prepuce

Answer 724

Posthitis in sheep Corynebacterium renale

Answer 725

Bovine herpes virus 1 Phaloposthitis in the bull Infectious pustular vulvovaginitis and abortion in the cow (see dry lab) Respiratory disease in the calf

Answer 726

neoplasm of the penis and prepuce Genital papillomas, or warts, on the penis seen in horses and cattle Viral cause In horses can progress to squamous cell carcinoma

Answer 727

seen in grey horses neoplasm

Answer 728

Equine rhinopneumonitis is caused by equine herpesvirus 1 (EHV-1) and less often by EHV-4, and is the most important viral cause of abortion in horses. Abortion usually occurs after 7 months of pregnancy and there is no corresponding maternal illness. the disease is diagnosed by a blood test or isolation of the virus from fetal tissues. Prevention is based on vaccinating at 5, 7, and 9 months of pregnancy as well as preventing exposure of pregnant mares to horses that attend shows or other equine events where they may have been exposed to the disease. fetus may showe fetus showing dark red patches on fetal membrane Equine viral arteritis may also cause abortion in horses 6 to 29 days after signs of infection appear. Signs of the disease include fever, swelling of the limbs, poor appetite, nasal discharge, and swelling of mammary glands. Stallions can be infected with the virus and carry the disease. Equine viral arteritis can be spread by sexual intercourse, artificial insemination with infected semen, or through the air. Infected horses usually recover without treatment. Prevention is based on vaccinating both the mare and the stallion.

Answer 729

the complete dissolution of nuclear components of a dying cell

Answer 730

the destructive fragmentation of the nucleus of a dying cell whereby its chromatin is distributed irregularly throughout the cytoplasm.

Answer 731

involves the shrinkage or condensation of a cell with increased nuclear compactness or density; karyorrhexis refers to subsequent nuclear fragmentation (Fig. 5-29, F). Pyknosis and karyorrhexis are degenerative changes that are often observed in nonseptic exudates.

Answer 732

stillbirth, mummification, embryonic death, and infertility often parvo destroys fetus and neonates mumification with progressive size difference spread by oral or venereal rout 30 days- fetal death and reabsorbtion 30-70 days- mumification after 7-0 days- noenatal death or healthy immune neonates

Answer 733

uclear or cytoplasmic aggregates which are stainable substances, usually proteins, and formed due to viral multiplication or genetic disorders in human beings these bodies are either intracellular or extracellular abnormalities and they are specific to certain diseases.

Answer 734

hypothalamus produces TRH pituitary produces TSH thyroid produces t4 and t3

Answer 735

stress prompts th hypothlamus to produce CRH CRH prompts the pituitary to produce ACTH ACT prompts the adrenal cortex to produce cortisol-

Answer 736

Dynamic systems: constant fluctuations in secretion and feedback allow maintenance of homeostasis Present in low quantities Variably stable/available to measure IGF-1 measured as proxy for GH in cats with acromegaly Can have significant diurnal variation “Normal” can vary significantly between species, age, time of day, time of year Variations post-treatment

Answer 737

Most common test type is sandwich ELISA Dynamic versus basal/static measurements Basal/static- Concentration of hormone at that particular time point E.g. Total T4, free T4, TSH Dynamic- Suppression testing: drug/synthetic hormone administered which should result in negative feedback, suppressing hormone production E.g. LDDST, HDDST Stimulation testing: synthetic stimulating hormone administered which should result in an exaggerated response of gland (hyperplastic/neoplastic) E.g. ACTH stimulation

Answer 738

Due to hyperplastic or neoplastic hyperthyroid gland- Over production of T3 and T4 Screening tests may show increased ALT Basal testing of T4 Total T4 concentration (TT4) highly specific for hyperT4 Easy and cheap, now available in house BUT, 10% hyperT cats have T4 within reference range Free T4 concentration (FT4) More accurate reflection of thyroid status Less readily available, more expensive, subject to sample handling errors Beware the sick euthyroid- can have normal t4

Answer 739

Quite possibly the most over diagnosed endocrine disease in dogs Age-related weight and behaviour changes Overlap with HAC and other diseases Serum concentrations of T4 decrease in older dogs naturally Basal tests- Total Thyroxine (T4) concentration Free Thyroxine (T4) concentration TSH concentration TGAA antibodies Expected results: Euthyroid dog: TT4 and FT4 within reference ranges Sensitive HypoT4: TT4 and FT4 low TSH increased Thyroglobulin antibodies negative or positive Dynamic testing: TSH stimulation Considered gold standard – but limited availability and expense of TSH

Answer 740

Do no harm Another overdiagnosed and potentially overtreated disease No single test for Cushing’s has both high sensitivity and high specificity – all are a compromise between the two Must have a strong clinical suspicion before performing testing PU/PD +/- PP Coat changes – alopecia, comedones (blackheads), thin skin Abdominal distension (‘pot belly’) – due to enlarged liver and weak muscles Lethargy, excessive panting, weakness Weight gain Prior tests: Haematology: Stress leukogram- execss cortisol Chemistry: increased ALP activity, hypercholesterolaemia Urinalysis: SG 1.001-1.030, proteinuria Urine cortisol:creatinine ratio (UCCR) Single test Creatinine accounts for changes in urine concentration Poor specificity (20%), high sensitivity (97%) Negative: HAC unlikely Dynamic tests- ACTH stimulation test Low-dose dexamethasone suppression test High-dose dexamethasone suppression test ACTH stim test Relies on the fact that in natural HAC, the adrenal cortex is either hyperplastic or neoplastic so increased in volume so capable of making more cortisol than normal High specificity (90%), moderate sensitivity (85% PDH and 50% ADH) Normal: Increased cortisol to expected level HAC: Increased cortisol beyond expected range (exaggerated response) False positives: Sick dogs with non-adrenal illness False negatives Certain drugs e.g. corticosteroids, progesterones, ketoconazole (+/- phenobarbital) Test of choice for iatrogenic HAC Chronic high doses corticosteroid (exogenous) results in adrenal gland atrophy and gland cannot respond to ACTH stimulation Low dose dexamethasone suppression test Relies on negative feedback to the pituitary gland so that in a normal animal, administration of a steroid will supress ACTH production and thus production of endogenous cortisol If an animal has a productive pituitary tumour (PDH) or adrenal tumour (ADH) the adrenal glands will ignore this negative feedback and produce cortisol regardless Moderate specificity (70%), high sensitivity (95%). Interpretation: Firstly, the presence or absence of Cushing’s syndrome is determined by examining the 8 hour result. An 8 hour cortisol value greater than 40 nmol/l is generally considered to represent a ‘positive’ result Typically in a dog with ADH, the adrenal tumour secretes cortisol autonomously and ACTH production is already suppressed, thus cortisol production is not suppressed in response to dexamethasone administration. The second step only applies in the positive cases and checks for evidence of cortisol suppression. In up to 60% of PDH cases, there will be marked suppression of cortisol (to <50% of the baseline value) at either 3 hours or 8 hours providing a way to differentiate between the two types of hypercortisolism. High dose dex suppression test

Answer 741

Cattle all ages – the tonsils, the last four metres of small intestine, the caecum, and the mesentery. Over 12 months – skull excluding the mandible but including the brains and eyes, and spinal cord. Over 30 months – vertebral column, excluding the vertebrae of the tail, the spinous and transverse processes of the cervical, thoracic and lumbar vertebrae, the median sacral crest and the wings of the sacrum, but including the dorsal root ganglia. Sheep and goats All ages – the spleen and the ileum. Over 12 months (or have a permanent incisor erupted) – skull including the brains and eyes, tonsils, spinal cord.

Answer 742

It is now against the law to let a dog be dangerously out of control anywhere. The law was changed so that people could be prosecuted if their dogs carried out an attack anywhere, including in the owner’s own home. The maximum prison sentence is 14 years for a fatal (human) dog attack 5 years for injury 3 years for an attack on an assistance dog

Answer 743

Prevents those who attack or injure service animals from claiming self defence Finn is a police dog who was stabbed whilst pursuing a suspect with his handler. Finn sustained serious stab wounds to the chest and head, but only criminal damage charges could be brought against his attacker

Answer 744

This will mean that puppies and kittens can no longer be sold by a third party seller such as a pet shop or commercial dealer, unless they have bred the animal themselves. Instead, anyone looking to buy or adopt a puppy or kitten under six months must either deal directly with the breeder or an animal rehoming centre. The law is named after Lucy, a Cavalier King Charles Spaniel who died in 2016 after being subjected to terrible conditions on a Welsh puppy farm

Answer 745

a legal concept It requires that the origin and history of any exhibit presented as evidence must be clearly demonstrated to have followed an unbroken chain from its source to the court. All persons handling the sample and the places and conditions of storage must be documented. This includes a note of the time, date, place and signatures where appropriate. This must include all specimen handovers and all key stages of processing.

Answer 746

a marrow disorder characterized by atrophy of hematopoietic and fat cells in the bone marrow with accumulation of gelatinous material. indicates extreme starvation

Answer 747

blood clot in left ventricle- no rigor mortis serous atrophy of fat no fat in abdomen, heart, kidneys a dn marrow no stromach in food indicates starvation food in stmach with emaciation indicates disease

Answer 748

inflamation of the lip

Answer 749

inflamation of the mouth

Answer 750

mesenteric vessels mesenteric arteries attach toi mesenteric border so insissions shoud be made in the anti-mesenteric border an infarction of one of these vessels will cause a wedge shaped, well demarcated, necrotic lesion- could be due to stronguus vulgaris in horse volvulus- twisted gut. cause dilation on oral side, necrosis of twisted segment- segmentally necrotic

Answer 751

The gastrointestinal microbiome is very complex Colonisation by an obligate pathogen (not usually found in gut) or overgrowth of a commensal (found in gut, normally not harmfull)? The pathogenesis of the infectious agent will affect appearance but generally intestines, at least acutely, for most will be: Hyperaemia- will look red, purposful build up of fluid for inflamatiion as opposed to congestion Fluid filled lumen- damage to enterocytes (lumen of digestive tract) upsets balence and causes fluid build up can be investigated by fecal culture- difficult with commensial microbes as they should always be there Enterotoxaemia

Answer 752

bacterial toxins absorbed into bloodstream from intestines Typically in veterinary species we are referring to various types of Clostridium perfringens: Types A to E All produce a different of combination of toxins Type D produces epsilon toxin: Typically seen in fat weaned lambs after sudden diet change/increase in grain = overeating disease. certain bacteria adapted for certian food sorce so increase in grqin feeeds these colonies Pore forming- -Enterocyte necrosis: Necrohaemorrhagic enteritis- sloughing of lining -Kidney tubular cell necrosis- kidney autolyses fater than carcus “pulpy kidney”= glucosuria -Increases vascular permeability: Petechial haemorrhages Pericardial effusion- clear to fibrinous fluid Brain oedema -> neurological signs- Blindness, headpressing, ataxia

Answer 753

Most viruses generally prefer to infect cells with rapid turnover as can use their replicative mechanisms to produce more virus GIT has constant cell turnover Some viruses take this one step further and stimulate prolific growth e.g. papilloma viruses -Stimulate the cell cycle In some cases inhibit innate cell-mediated immunity Hyperplastic lesions -> papilloma (and sarcoids), often regress on their own but can get secondary infections Malignant transformation in some cases-Squamous cell carcinoma, Cervical carcinoma in humans sarciods in horse caused by papilloma virus from cows Due to purpose of the GIT, viral shedding and therefore infectivity is high: Faeco-oral transmission Saliva- rabies ect Many viruses of significant veterinary importance spend all if not most of their transmission cycle within the GIT can cuase: erosion, ulceration, vesicles- foot and mouth, pustulates

Answer 754

Loss of surface epithelium and extends into lamina propria/submucosa

Answer 755

Fluid filled space between layers of the epithelium Blister Also common in auto-immune diseases foot and mouth a disease that causes blistering of the skin and the inside of the mouth, nose, throat, eyes, and genitals. The disease is rare in the United States. Pemphigus is an autoimmune disease in which the immune system mistakenly attacks cells in the top layer of the skin (epidermis) and the mucous membranes.

Answer 756

As per vesicle but contains necrotic material/pus

Answer 757

impation foreign body herniation- chewing open of spay wound

Answer 758

megaesophagus ect

Answer 759

arrest of intestinal motility in the absence of an obstruction Clinical signs- Colic Distension Reflux/regurgitation- more common in horses Vomiting- carnicores Neuropathic- Myasthenia gravis- Clostridium botulinum -> Grass sickness. the toxin kills off neurons. causes impaction of colon and dry faecal balls. build up of fluid in proximal GIT Inflammation- Ileus common post surgery and stress- rabbits esspecially

Answer 760

Non GI causes of vomiting Uraemia Neurological Addison’s- Hypoadrenocorticism Intermittent v+d+ Glucocorticoids maintain normal gastrointestinal mucosal integrity and function Intestinal epithelial barrier disruption leads to permeability defects and the subsequent interaction of intestinal immune cells with the luminal contents. Activated immune cells release pro-inflammatory cytokines, such as TNF. In turn, TNF results in tight junction (TJ) disruption and intestinal epithelial cell (IEC) apoptosis and thereby exacerbates local inflammation. TNF also directly stimulates IECs to synthesize and release immunoregulatory glucocorticoids (GCs) to counter-balance excessive tissue damage. GCs act via the glucocorticoid receptor (GR) to inhibit TNF-mediated tissue damage in a negative feedback loop. The GR also inhibits pro-inflammatory transcription factors, including NF-κB, AP-1, and STATs leading to the resolution of the inflammation.

Answer 761

can be of endoderm- epithelium: squamus cell carcinoma in mouth, oesophagus, skin and stomach or squamus cell portion of stomach in horses glangular epithelium- lining of gut, adenoma(benign), adenosarcoma(malignant) git is immune organ- payers patches- lymphoma can be of mesoderm- smooth muscle- layomyoma (benigns0, leyomyosarcoma (malignant) serosa- plur- MESOTHELIUM- MESOTHELIOMAS many autonomic nerves- uncommon to get neoplasms as they dont divide endocrine tumours

Answer 762

Presents as severe inflammation of the oral cavity Most commonly affects the caudal oral mucosa:-palatoglossal arches (fauces), -alveolar and buccal mucosa of the caudal oral cavity, -less commonly soft palate and dorsal aspect of the caudal tongue- The hard palate, labial mucosa and sublingual mucosa are usually spared Not fully understood –probably several factors: -Dental and periodontal disease, -Altered immunological response, -Infections: -feline calicivirus, -FeLV, FIV, feline herpes virus-1, -Pasteurella multocida, Bartonellaspp., Mycoplasma felis.. Usually affects adult cats •Extremely painful •Diminished food intake •Weight loss •Ptyalism •Halitosis •Unkempt appearance histology for unclear clinical presentations for distinguishing between inflammation and squamous cell carcinoma (SCC) histpathology- Marked lymphoplasmacytic inflammation with prominent numbers of plasma cells •Localised to the mucosa, but can extend into the submucosa (occasionally also sialadenitis, myositis) •Mott cells = plasma cells with numerous globular cytoplasmic inclusions composed of immunoglobulin (Russell bodies)- grape like appearence Hyperplasia and erosion of overlying epithelium •Migration of neutrophils into the epithelium •Variable numbers of macrophages, mast cells treatment is to take out teeth- linked to poor teeth and therefore removal of presence of plauque may help

Answer 763

Indolent Ulcer (Rodent ulcer, Eosinophilic Ulcer) Eosinophilic plaque Eosinophilic granuloma Linear granuloma group of lesions - skin, oral cavity and mucocutaneous junctions histopathological findings = reaction pattern not specific disease associated with hypersensitivities: flea bite allergy** food allergy atopy drug reactions other potential causes or contributory factors: bacterial infection foreign body reactions irritant reactions self-trauma endoparasites genetic predisposition In cats, it affects a broad age and breed range with common sites being: -dorsal surface of the tongue, -palate, -mucocutaneous junction of the rostral lips In dogs, it is over-represented in Siberian huskies and Cavalier King Charles spaniels with common sites being: -palate, -less commonly tongue, lips, other mucosal sites A complex of inflammatory diseases that represents a group of similar hypersensitivity reactions to various antigens (environmental, ingested materials, parasitic e.g fleas) can be treated by treating these Several clinical presentations/terms: -linear granuloma ,-eosinophilic plaque/granuloma, -collagenolytic granuloma, -indolent ulcer histopathology- Variable numbers of eosinophils (can be a mixed inflammatory population with eosinophils) *↑ neutrophils in ulcerated areas *Collagenolysis *Cytology can often provide a diagnosis, so histology is not necessarily needed The pathologist provides a diagnosis of eosinophilic or mixed inflammation (macrophages, lymphocytes) with eosinophils in more long term chronic cases-In highly indicative cases (based on histology and clinical history), the pathologist can mention EGC in the comment

Answer 764

infection of bone including the marrow The source of infection can be: -hematogenous(bacteraemia), -implantation(open jaw fractures, contamination of surgical sites, bite wounds, gunshot wounds), -local extension (from an infected tooth or periodontal tissues) Common infectious agents are: -Staphylococcusspp., -Streptococcusspp., -Truperellapyogenes, -Nocardiaspp., -Coccidioides immitis, -Cryptococcus neoformans Osteomyelitis and destructive malignant neoplasms can have a similar appearance! •Several things need to be taken into consideration: -clinical examination, -diagnostic imaging, -histology, -microbiology

Answer 765

*The most common non-odontogenicoral neoplasm in cats *Can present as a proliferative, ulcerated lesion or a non-healing wound *Often invades underlying bone *Can metastasize, but usually later on *Can mimic osteomyelitis on X-ray histopathology- Keratin pearls = neoplastic keratinised squamous cells forming concentric layers *Neoplastic cells in SCC extend past the basement membrane into the underlying stroma*The majority of them is either well or moderately differentiated*Dysplastic changes of the epithelium may possibly evolve into SCC The 2ndmost common non-odontogenicoral neoplasm in dogs Risk factors: UV damage – white fur** Pinnae, eyelids, nasal planum Locally invasive and destructive Variable appearance: plaque-like, ulcerated, exophytic nodules, scabby, red, inflamed….. Temporal progression, can be slow Uncommonly metastasize - local lymph node if it occurs it is usually a late-stage feature

Answer 766

Lesions most often occur on the buccal mucosa and lateral lingual mucosa opposite to larger tooth surfaces Affected mucosa is often depigmented and mirrors the shape of the associated tooth → contact stomatitis Predisposed breeds: greyhounds •Poorly understood, most likely due to inflammatory reaction to persistent plaque bacterial biofilm that damages the mucosa •Clinical signs:-drooling,-halitosis, -reluctance to eat Histopathology- •Lichenoid and perivascular infiltrate of B and T lymphocytes and plasma cells •Often ulcerated epithelium, intercellular oedema, transmigration of neutrophils and T lymphocytes and sparse necrotic/apoptotic epithelial cells •Granulation tissue formation beneath ulceration

Answer 767

The most common non-odontogenicoral neoplasm in dogs •Mean age: 10.5 –12 years •Early and high metastatic rate •Often invades underlying bone (50%) •Very rare in cats •Melanocytoma, benign neoplasm of melanocytic origin, is very rare in the oral cavity histopathology- •Mitotic Index > 4/10 HPF •↑ nuclear atypia •Ki67 > 19.5 - proloferation measure •↓ pigmentation Amelanotic MALIGNANT MELANOMA- Immunohistochemistry:-Melan A-PNL2(slightly ↑ sensitive than Melan A)

Answer 768

The 3rdmost common non-odontogenicoral neoplasm in dogs •Mean age: 8 years •Maxillary and palatal lesions are more common than mandibular •Locally aggressive, invasive and destructive •Low metastatic rate The 2ndmost common malignant oral neoplasm in cats (after SCC) Histopathology- Fibrosarcomaoramelanoticmalignantmelanoma? FinaldiagnosiswithIHC:-vimentin+-MelanA --PNL2 -

Answer 769

Most often arises from the maxillary gingiva•Most frequent in large breed dogs, especially Golden retrievers•Biologically very aggressive histopathology-ery bland histology reminiscent of fibrous connective tissue•Histopathology cannot distinguish between H/L FSA and fibrous gingival hyperplasia or fibroma•Clinicopathological correlation is VITAL!

Answer 770

•A common most likely reactive gingival lesion •Mean age: 8.5 years •Rostral maxilla is the most common site •Locally invasive •Very good prognosis even after marginal excision histopathology- •Three main components:-proliferative mesenchymal cells embedded in a collagenous stroma reminiscent of periodontal/gingival ligament,-cemento-osseous matrix,-odontogenic epithelium

Answer 771

•The most commonodontogenicneoplasm in dogs •Mean age: 8.8 years •Rostral mandible is the most common site •Local invasion of underlying bone •Does not metastasise Histopathology- Cardinal histologic features of odontogenic epithelium:-palisading of the basilar epithelium,-palisading epithelial cells have antibasilarnuclei,-palisading epithelial cells have a basilar clear zone within the cytoplasm,-odontogenic islands have central areas reminiscent of stellate reticulum (not present in CAA!) •Can morphologically mimic SCC•No reliable IHC markers for odontogenic epithelium in veterinary medicine

Answer 772

Inflammation of the mucosa Often due to acid reflux- Weak sphincter? Hernia - stomach herniates into oesopahgus– most common, especially in barachycepahlic breed Oesophageal mucosal metaplasia- Strat squamus epithelium to columnar Can be iatrogenic- Doxycycline in cats Regurge during GA May result in stricture

Answer 773

stricture formation Choke- food lodges in oesophagus

Answer 774

disease of oesophagus Vascular ring anomaly German Shepherd dogs Results in dilated oesophagus cranial to constriction foetal vasculatue that should regress persists and forms tricture across oesophagus

Answer 775

anomolous/ ideopathic disease of oesophagus Another important cause of megaoesophagus Congenital and idiopathic forms- congenital form rare Idiopathic due to antibodies against- acetylcholine receptor This can be secondary tumours of the thymus Aspiration pneumonia a risk

Answer 776

disease of abomasum Bacterial- Clostridium septicum- Braxy Clostridium sordelli Viral- Rarely just the abomasum BVD Malignant catarrhal fever Parasitic

Answer 777

Gastritis as a single entity is rare in veterinary species Inflammatory bowel disease The stomach has a unique microbial flora due to the pH Helicobacter spp are important in humans and ferrets (H. mustelae)- Associated with ulceration Low numbers are consider unremarkable on gastric biopsies from dogs and cats

Answer 778

Primarily an issue in horses and pigs Complicated and unclear pathogenesis- Inappropriate feed Stress NSAIDs Pigs- Non-glandular oesophageal portion Ruminal ulcers in cows typically associated with ruminal acidosis- Caudal vena cava syndrome Fungal overgrowth Abomasal ulceration cause unclear

Answer 779

Hardware disease Wire or similar penetrates wall of reticulum Pathophysiology varies from localised transmural inflammation of the wall of the reticulum to peritonitis to pericarditis Clinical signs initially include -ruminoreticular atony moderate ruminal tympany, decrease in milk production pyrexia abdominal pain -arched back, erect hairs at the withers, anxious expression, reluctance to move, and an uneasy, careful gait pain going down hill whithers/pole test Chronically ill to sudden death from heart failure

Answer 780

metabolic problem of the stomach In renal failure, nitrogenous toxins build up in the blood- movement of calcium and interaction with digestive acid in the stomach results in deposition of calcium in stomach- Ulceration and mineralisation

Answer 781

Stomach tumours are generally rare in veterinary species Squamous cell carcinoma in horses -> in glandular stomachs- Adenocarcinoma -> Leiomyoma/sarcoma Gastrointestinal stromal tumours Lymphoma Carcinoids

Answer 782

Left or right displaced abomasum High yielding dairy cows Multifactorial- Hypomotility -Hypocalcaemia,High concentrate diet RDA more commonly seen within 1 month of calving LDA more common than RDA results in Metabolic alkalosis with hypochloremia and hypokalemia

Answer 783

Bloat is a clinical syndrome relating to the clinically appreciable distension of the abdomen due to distension of the stomach Typically due to the inability of liquid or gas to exit the stomach Gastric dilation and gastric dilation/dilatation and volvulus (GDV)- bloat with gas and also twinst in stomach Gastric dilation/distension can occur if gorge on kibble In cows referred to as ruminal tympany In the cow there are two forms; Frothy (primary) Gas (secondary) Frothy Typically due to consumption of legumes- Lower ruminal ph (normal is 6.5 to 7.5) Blocks eructation Acute and deadly Gas- Due to physical or physiological inability to eructate;Choke, Vagal indigestion (problem with vagal nerve so stomach isnt inervated proerly) More chronic Difficult to detect post mortem- Bloat line= loss of congestion in stomach and caudal trachea as stomach blocks blood flow can measure rumen ph for frothy bloat

Answer 784

Gastric dilation/distension can occur if gorge on kibble GDV is typically gaseous with some liquid and food Pathogenesis incompletely understood Volvulus occurs first? The pylorus and duodenum first migrate ventrally and cranially. A volvulus of >180° causes occlusion of the distal oesophagus. Compress vasculature- Caudal vena cava Stomach and splenic -> necrosis Fluid “lost” into the stomach- Metabolic acidosis Hypovolaemia shock- use lactate to determine prognosis Severely ill, clinical emergency DIC- dogs can go into disseminated intravascular coagulation sue to the stasis of blood due to twist and the endothelial damage

Answer 785

Gastric dilation as a primary disease rare in horses Will quickly fill with fluid in cases of obstructive colic Also will occur in motility disorders, Most well known would be grass sickness- Clostridium botulinum Autonomic neurones lost No peristalsis

Answer 786

isseminated intravascular coagulation (DIC) is a rare but serious condition that causes abnormal blood clotting throughout the body's blood vessels.

Answer 787

Gaseous distension of the GIT is a common post mortem finding, especially farm animals May perforate if left long enough Did this perforation occur before or after death? INFLAMMATION CANNOT OCCUR AFTER DEATH Gross- Fibrin Histo- No cellular response

Answer 788

Displacements/obstructions- motility Malabsorption(villus atrophy)- loss or damage to brush borders Maldigestion- bile duct issues- osmotic dihorea intestine wall efficient with absorbtion but this also allows infection into blood stream

Answer 789

•Abdominal pain (colic in large animals) •Vomiting •Diarrhoea -acute -chronic ± weight loss/ascites •Constipation However: may present together or be part of a systemic condition

Answer 790

Acute or chronic Displacements: •Volvulus (twisting on mesenteric axis)- in caecum •Torsion (twisting on long axis)- involves mesentary •intersuseption- intestine telescopes on itself •Obstruction-internal (e.g. foreign body, parasites, tumour, intussusception)-external (e.g. strangulating lipoma) •Thin walled veins get compressed •Venous congestion•Ischaemic infarction •Necrosis • decreased Gut barrier function (bacterial translocation/endotoxaemia) •Obstruction proximal •Perforation •Acute fibrinous/suppurativeperitonitis rupture

Answer 791

Presentation generally acute and severe no intestinal absorbion happening distaly stomach cannot empty Fluid and gas above obstruction •vomiting •metabolic alkalosis (loss of acid in vomitus) •dehydration •reduced renal flow and resultant uraemia

Answer 792

•generally less acute than upper intestinal tract (increased fluid resorptionproximal to obstruction reduced vomiting) •Pressure (fluid and gas) ➔-ulceration and infarction ±perforation-haemorrhage/peritonitis •Eventual metabolic acidosis due to dehydration and catabolism of fat and muscle (producing ketoacids)

Answer 793

Four basic mechanisms: 1. Altered structure / permeability (malabsorption) 2. Altered epithelial cell transport (secretory diarrhoea) 3. Osmotic effects (e.g. maldigestion)- no proper enzymatic digestion of certain components and large molecules draw water out 4. Altered motility The above mechanisms can operate in the small intestine, large intestine or both leads to: Loss of water Dehydration Haemoconcentration Hypovolaemic shock Loss of ions (principally sodium, potassium and bicarbonate): Metabolic acidosisHypokalaemia

Answer 794

Often involves infectious disease (esp. young animals) Viruses (e.g. rotavirus, coronavirus and parvovirus) Bacteria (e.g. Campylobacter, Salmonella, Clostridium spp.) Endoparasites (e.g. cyathostomes) Protozoa (e.g. cryptosporidiosis and coccidiosis) Many more!!! Remember zoonotic potential

Answer 795

different infectiomn swill attack different parts of structures e.g parvo attacks intestinal cryp cuasing massive damage where as ecoli target only the microvillus

Answer 796

lacks own equipment for replication targets intestinal cells that are activly replicateing- crypt, payers patches, bone marrow in kittens cuases massive damage as reduces capibility for repair

Answer 797

produce exotoxins- diffuse damage as opposed to multifocal

Answer 798

larvae are quiesent in muscosa mass emergence in winter/ early spring causes extreme and sevear multifocal damage diohroa through malabsrbtion

Answer 799

Chronic enterocolitis :•Lymphoplasmacytic •Eosinophilic •Granulomatous Lymphangiectasia Endoparasitism Neoplasia Grass sickness

Answer 800

•Syndrome associated with persistent intestinal inflammation of unknown cause- idiopathic •Subdivided according to predominant inflammatory cell: •lymphoplasmacytic enteritis, •eosinophilic enteritis

Answer 801

consiquence of persistant inflamation in intestine (i)Increased permeability to plasma proteins -lost to intestinal lumen (ii) Chronic inflammation -lymphatic blockage Main protein lost is albumin. Loss exceeds liver synthesis ➔hypoalbuminaemia➔lower plasma osmotic pressure➔oedema and ascites(wasting + emaciation may also be present)

Answer 802

consiquence of persistant inflamation in intestine (i)Increased permeability to plasma proteins -lost to intestinal lumen (ii) Chronic inflammation -lymphatic blockage Main protein lost is albumin. Loss exceeds liver synthesis ➔hypoalbuminaemia➔lower plasma osmotic pressure➔oedema and ascites (wasting + emaciation may also be present due to lack of absorbtion) Primary intestinal lymphangiectasia (PIL) is also called Waldmann's disease. It is a rare disorder that causes you to lose special proteins from your intestine. The intestine is connected to lymph vessels.

Answer 803

blunting/stunting/fusion

Answer 804

can result in secondary protein-losing enteropathy dissrups arcayecture and therefor absorbtion

Answer 805

inflamitory cells cause thickening jhones disease- diffuse thickening necrosis impeads nutrient absorbtion protien loss pipe stem diorhoea histeopathology- macrophages- form multinuclead giant cell becuase they cannto phagocytose mycobacterium

Answer 806

Functional problems may relate to: 1.Malabsorption (e.g. cyathostomiasis) 2.Obstruction (e.g. ascariasis)- caused by sheer number of worms 3.Vascular compromise (e.g. large strongyle disease)- necrososis, affect mesenteric vasculature and cause infarctions

Answer 807

unknown agent- effects horses at pastur, possibly botulinum agent releasing toxins Damage to neurones results in complete lack of peristalsis •Nasogastric reflux and oesophageal ulceration •Gastric dilation and rupture histologicaly the neurons will be few and chromatolytic (pink) actute- 48 hours chronic- greater than a week Weight loss Muscle tremors Rhinitis sicca Dysphagia Patchy sweating Constipation Large colon impaction often fatal

Answer 808

Terminal hypostasis will result in a congested liver Diffusely reddened and heavy liver that oozes Barbiturates exacerbate this Important to differentiate from chronic heart failure

Answer 809

Terminal hypostasis will result in a congested liver Diffusely reddened and heavy liver that oozes Barbiturates exacerbate this Important to differentiate from chronic heart failure

Answer 810

The liver is a very metabolically active organ After death hepatocytes may lyse and release enzymes = autolysis Macroscopically early autolysis may not be obvious with time tissue becomes paler, soft, friable and may exude fluid mucosal linings may slough off easily e.g. intestine Microscopically early autolysis cells will swell cytoplasmic and nuclear detail are lost cells lose their cohesion to each otherkkmmmm no inflammatory response Exacerbated by influx of post mortem overgrowth of bacteria = putrefaction Macroscopically Carcass blown up Gas bubbling Psuedomelanosis A blue-green to block post mortem discoloration due to bacterial breakdown of haemoglobin produces hydrogen sulphide. Microscopically Bacteria typically rods in farm animals (Clostridia) No inflammation

Answer 811

The liver is a large organ so a significant proportion must be destroyed before clinically appreciable true failure As with any epithelial organ, cysts are relatively common and may or may not be pathological Hepatocellular adenomas will need to become very large or rupture before causing an issue

Answer 812

Due to the unique blood supply, type of endothelia and architecture of the liver, oedema does not occur Congestion however is very common Infarction is very rare in the liver and tends to occur at the tips Centrilobular (zone 3) hepatocytes are the furthest away from oxygenated blood and are also metabolically the most active, therefore are sensitive to cardiogenic failure Chronic passive congestion due to chronic heart failure will result in chronic low oxygen delivery to the centrilobular hepatocytes Grossly this appears as a zonal pattern with congestion of the central veins and pallor of the centrilobular hepatocytes The centrilobular hepatocytes are pale due to hydropic degeneration (cell swelling – reversible) Chronically these centrilobular hepatocytes may undergo necrosis and may be replaced by fibrosis which grossly appears as a “nutmeg” liver Chronic anaemia will also cause loss of centrilobular hepatocytes Liver lobe torsion is generally rare in veterinary medicine, except in rabbits Telangiectasia is benign distension of sinusoids by blood seen most frequently in the cow. Blood flow may also be compromised secondarily to diaphragmatic hernias Portosystemic shunts Blood from the portal system bypasses the liver Due to anomalous vessel(s) Can be congenital (Yorkshire Terrier) or acquired (Spaniels due to chronic liver disease) Extra-hepatic (small breed) or intra-hepatic (large breed) Clinically Stunted growth Hepatic encephalopathy Biochemistry: Elevated serum bile acids, hypoalbuminemia, hyperammonaemia, hypoglobulinaemia, hypoglycaemia, decreased BUN, hypocholesterolemia Urinalysis: Ammonium biurate crystals in alkaline urine Haematology: mild to moderate microcytic, normochromic, nonregenerative anaemia Grossly the liver is atrophic as lacking growth stimuli

Answer 813

vascular pathology of liver Blood from the portal system bypasses the liver Due to anomalous vessel(s) Can be congenital (Yorkshire Terrier) or acquired (Spaniels due to chronic liver disease) Extra-hepatic (small breed) or intra-hepatic (large breed) Clinically- Stunted growth Hepatic encephalopathy Biochemistry: Elevated serum bile acids, hypoalbuminemia, hyperammonaemia, hypoglobulinaemia, hypoglycaemia, decreased BUN, hypocholesterolemia Urinalysis: Ammonium biurate crystals in alkaline urine Haematology: mild to moderate microcytic, normochromic, nonregenerative anaemia Grossly the liver is atrophic as lacking growth stimuli

Answer 814

The liver can be exposed to infectious agents through three main routes Haematogenous Biliary (ascending) Direct extension Neonates also have a direct connection between umbilicus and liver The liver receives 100% of the blood flow from the GIT Defence Kupffer cells Resident macrophages IgA secreted into bile viral- Herpes- Typically affects foetus and neonates Characteristic intranuclear viral inclusion bodies Adenoviruses- Canine infectious hepatitis Chickens bacterial- Innumerable types of bacteria may infect the liver Bacteria from the GIT May initially be peri-portal Tyzzer’s disease Clostridium pilliforme Foals and laboratory species (gerbils) Abscessation common Ruminal acidosis damages the rumen mucosa, resulting in translocation of Fusobacterium necrophorum into the portal circulation-> hepatic abcesses -> caudal vena cava syndrome Haematogenous bacteria Typically random necrosis- salmonella, Listeria, Clostridia, Yersinia Mycobacteria – pyogranulomas, Ziehl-Neelsen Leptospirosis Campylobacter (aborted lambs) Leptospirosis Clinical signs associated with leptospirosis vary and depend on the serovar and the host. In maintenance hosts, leptospirosis generally is characterized by a low serological response, relatively mild acute clinical signs, and a prolonged renal carrier state which may be associated with chronic renal disease. In incidental hosts, leptospirosis can cause severe disease. Dogs Young > old Serovars icterohemmorrhagiae and canicola were believed to be responsible for most clinical cases of canine leptospirosis and after a bivalent serovar-specific vaccine against canicola and icterohemmorrhagiae came into widespread use, the incidence of "classic" leptospirosis in dogs decreased. Clinical signs: fever, inappetence, vomiting, abdominal pain, diarrhoea, PUPD. Depending on strain and host response, pathogenesis can be primarily due to hepatic or renal dysfunction or a combination. Whilst the renal consequences of lepto were covered in a previous lecture, the liver is another major organ damaged during leptospirosis. The degree of icterus in canine disease usually corresponds to the severity of hepatic necrosis. Cattle The icterus and haemoglobinuria that develop in cattle with leptospirosis results from a specific haemolytic toxin produced by serovar pomona. Chronic canine hepatitis- Enigmatic disease of incompletely understood pathogenesis Spaniels, Dobermans and Labradors all over-represented, therefore genetic factors implicated May be secondary to chronic infection, such as lepto, or copper toxicosis (see later) Clinically the animal will have raised liver enzymes Grossly characterized by a small liver with nodules of hepatocyte regeneration and hyperplasia, separated by bands of fibrosis Proxy for cirrhosis Histopathology reveals periportal inflammation predominantly with portal areas bridged by fibrosis Feline triaditis- In dogs, the common bile duct joins the duodenum at the major duodenal papilla, separately from the pancreatic duct. An accessory pancreatic duct joins the duodenum at the minor papilla in most dogs though anatomic variation exists. In cats, the common bile duct fuses with the pancreatic duct before entering the major papilla. Only 20% of cats are estimated to have an accessory pancreatic duct The canine CBD is 3mm in diameter and the feline CBD is 4mm in diameter Probably due to their unique anatomical features of cats, whenever the intestine is inflamed, so too will be the pancreas and/or biliary tree Cats are typically impressively jaundice Likely post-hepatic Histopath reveals portal and peri-portal inflammation, indicative of ascending infection The liver can be affected by helminths in two ways Target organ Trematodes Cestodes Visceral migrans Nematodes fungal- histoplasmosis protozoal- toxoplasmosis

Answer 815

Enigmatic disease of incompletely understood pathogenesis Spaniels, Dobermans and Labradors all over-represented, therefore genetic factors implicated May be secondary to chronic infection, such as lepto, or copper toxicosis (see later) Clinically the animal will have raised liver enzymes Grossly characterized by a small liver with nodules of hepatocyte regeneration and hyperplasia, separated by bands of fibrosis Proxy for cirrhosis Histopathology reveals periportal inflammation predominantly with portal areas bridged by fibrosis

Answer 816

In dogs, the common bile duct joins the duodenum at the major duodenal papilla, separately from the pancreatic duct. An accessory pancreatic duct joins the duodenum at the minor papilla in most dogs though anatomic variation exists. In cats, the common bile duct fuses with the pancreatic duct before entering the major papilla. Only 20% of cats are estimated to have an accessory pancreatic duct The canine CBD is 3mm in diameter and the feline CBD is 4mm in diameter Probably due to their unique anatomical features of cats, whenever the intestine is inflamed, so too will be the pancreas and/or biliary tree Cats are typically impressively jaundice Likely post-hepatic Histopath reveals portal and peri-portal inflammation, indicative of ascending infection Cholangitis Pancreatitis Inflammatory bowel disease

Answer 817

Common liver fluke of ruminants Indirect life cycle Three syndromes Acute fasciolosis, normally seen in sheep, is caused by large numbers of juvenile fluke migrating through the liver. These cause extensive haemorrhage and damage to the liver parenchyma. Animals are typically weak, and anaemic, often with palpably large livers, abdominal pain, ascites and sudden death is common. Chronic fasciolosis occurs in both sheep and cattle and occurs several months after moderate intake of infective cysts. Chronic disease is associated with adult fluke in the bile ducts. Anaemia, loss of appetite and gradual weight loss are common clinical signs. Infection also has an impact on fertility, growth rates and milk production. Black disease (Clostridium novyi) in sheep and bacillary hemoglobinuria (C. hemolyticum) in cattle (and sheep). Migration of immature flukes through the hepatic parenchyma may result in the generation of necessary ischemic conditions for the proliferation of clostridial spores, already within the liver, to proliferate. Once activated the clostridial bacteria produce toxins, resulting in necrosis in the liver and death in sheep with black disease or intravascular haemolysis with associated anaemia and haemoglobinuria in cattle.

Answer 818

Echinococcus granulosus parasitizes canids as the definitive host, and the intermediate host is a large domestic species, such as cattle, sheep and horses. Canids pass the proglottids in areas where these animals graze, and upon ingestion the embryos develop into hydatid cysts. The cysts are most commonly found in the liver and lungs, although other organs can be infected; they may never result in clinical disease, but can result in carcass condemnation at time of slaughter. E. multilocularis has a predominantly canid-rodent life cycle and has a more fulminant disease process wherein the liver can become completely effaced by cysts.

Answer 819

Because of its function and exposure to portal blood flow, the liver is a major organ affected by toxins. Centrilobular hepatocytes are most commonly affected, as most toxins are not truly toxic until metabolised by cytochrome P450. Few toxins are toxic without metabolism and will thus cause periportal necrosis. An inexhaustive list of hepatotoxins include Plants and similar Blue-green algae Ragwort (pyrrollizidine alkaloids) Amanita mushrooms Mycotoxins Chemical/drug Xylitol Carprofen Acetaminophen/paracetamol Whilst copper is an essential cofactor of many cellular processes, it is also a toxicant at high enough levels resulting in free radical formation Acute death primarily in ruminants due to haemolytic crisis and acute liver necrosis sheep fed cattle feed and/or deficient in molybdenum Gross – icterus, multifocal pan-lobular hepatic necrosis and gunmetal blue kidneys Chronic Bedlington Terriers have a defect in a copper transport gene, may be other breeds too All dogs with CCH should have copper levels tested Copper levels in dog food too high? Because of the liver’s capacity to repair, chronic low grade toxicosis will result in regenerative nodules and fibrosis (see CCH slide) With ragwort toxicity, the alkylating toxins prevent cell division, resulting in characteristic megalocytes with huge nuclei Generally the liver is a good tissue to collect fresh samples from for acute toxicology sampling, and also from chronic copper levels (see wet lab). Cf: fat for chronic toxicosis.

Answer 820

Fatty liver disease/ketosis/twin lamb disease/hepatic lipidosis/steatosis Terms used for lipid deposition in the liver Physiology of lipid metabolism - recap Lipid is delivered to the hepatocyte from dietary sources or body fat stores in the form of free fatty acids (FFAs). A small amount of FFAs are also synthesized in the hepatocyte itself from acetate. Some of the FFAs are utilized for the synthesis of cholesterol and phospholipids, and some may be oxidized to ketone bodies (1). Most of the intracellular FFAs are esterified to triglycerides (2). Once triglycerides are produced, they must be complexed to a lipid acceptor protein (or apoprotein) prior to export from the cell (3) as lipoproteins. This requires protein and energy Triglycerides may accumulate if the balance between the synthesis of triglycerides and their utilization or mobilization is deranged. When intracellular triglycerides accumulate, a fatty liver results. Whilst hypoxia and toxins such as aflatoxins that affect protein synthesis in the liver can cause this, one of the main times to see this is when an animal can no longer rely on glucose as an energy source and free fatty acids are thus mobilised from adipose tissue as an alternative energy source This is an example of reversible injury

Answer 821

Gall bladder mucocele Border Terriers Kesimer, Mehmet, et al. "Excess secretion of gel-forming mucins and associated innate defense proteins with defective mucin un-packaging underpin gallbladder mucocele formation in dogs."

Answer 822

Glycolysis/Gluconeogensis Fatty Acid metabolism Bile Acid excretion Excretion of bilirubin Detoxification of blood Elimination of ammonia Production of plasma proteins Albumin Clotting factors

Answer 823

lethargy/inappetance weight loss colic photosensitisation- dermatitis and sunburn. pigments desposited by the liver are photosensitising agents encephalopathy- high amonia levels effect neurotransmitters- results in neuro signs: ataxia ect diarrhoea jaundice- slight jaundice can also be caused by not eating as horses do not have a gall bladder. ecpression of ligand that binds billuruben is linked to eating/grazing oedema coagulopathy ≥70% of liver function must be lost before insufficiency occurs Therefore: mild or no clinical signs do not rule out liver disease signs of insufficiency indicate severe damage and poor prognosis aim to investigate and treat early cases (subclinical?) ALT is NOT a good indicator of liver function in horses and other herbavores GLDH much more specific in horse

Answer 824

Serum liver enzymes indicate the presence of liver disease only Functional assays (BAs) indicate presence of disease and give some indication as to severity Neither will provide specific information on what is causing the liver disease BIOPSY is essential for gaining information regarding aetiology Guides treatment options Provides more accurate prognosis

Answer 825

Special diets are only required if the liver is failing Liver disease (in the absence of failure) does not require special dietary management The liver controls nutrient storage/supply feeding “little and often” seems sensible High dietary protein can exacerbate hepatic encephalopathy (neurologic signs relating to high blood ammonia) however protein restriction causes muscle breakdown advice to humans is to eat vegetarian protein! No need for B vitamins (if eating OK) and iron is hepatotoxic! Supplementation with vits A,D,E,K may be helpful

Answer 826

twisting on mesenteric axis)

Answer 827

Virulence is the ability of a microbe to cause pathological effects Some microbes are completely avirulent- Commensal bacteria of the gut Some microbes are only virulent under the right circumstances Clostridium difficile A commensal of the GIT in rabbits Antibacterial-induced dysbiosis will cause overgrowth and disease Most diseases we discuss in veterinary medicine are caused by obligate pathogens The disease cannot replicate or spread without causing disease Ebola virus Enveloped virus that takes its envelope from the host cell, killing it in the process The bodily fluids produced by this mass necrosis and haemorrhage are the infectious source for the next person Some microbes vary depending on strain Example: Newcastle disease virus Highly virulent/velogenic strains cause acute infections with high mortality Mesogenic/intermediately virulent strains cause respiratory disease in young chickens and decreased egg production Lentogenic/avirulent strains cause mild respiratory infection or give no symptoms in poultry

Answer 828

Any gene product of a microbe that enables infectivity, colonisation and/or spread May facilitate: Adherence (e.g. UPEC P-pilus) Invasion (e.g. Salmonella T3SS) Immune evasion (e.g. Trypanosome variant surface glycoproteins (VSG)) Immune suppression (e.g. Influenza NS1 protein) Acquisition of nutrients (e.g. bacterial siderophores to acquire iron)

Answer 829

The first step in infection is binding to a host cell Bacteria have adhesins known as pilli and fimbrae- Uropathogenic Escherichia coli (UPEC) Viruses have specific ligands for specific cell receptors SARS-CoV-2 binds to ACE2 Haemagglutinin in HPAI

Answer 830

Microbes colonizing a mucosal surface then need to cross the mucosa In the GIT this is typically done at the site of MALT- Mucosal-associated lymphoid tissue Only site in GIT not covered by mucous This can be done in one of seven ways M-cell trafficking – PCV2 Intercellular – Leptospirosis Transcytosis – Erysipelas Dendritic cell sampling – Sheeppox Lymphocyte trafficking – Rhodococcus equi Macrophage trafficking – Rhodococcus equi Neuronal – Herpesviruses

Answer 831

Transcytosis is a normal cellular process Endocytosis at one side of the cell (1), moving through the cell cytoplasm in a membrane covered vesicle (2), then exocytosis out the other side (4). In the healthy animal is used to transport macromolecules from one side of a cell to the other There are three main types of endocytosis Microbes typically hijack the receptor-mediated type or can be phagocytosed then evade destruction

Answer 832

Microbes can spread throughout the body by two main methods Passive/cell free within blood or lymphatics Relatively rare – typically eukaryotes Leukocyte trafficking Most common

Answer 833

Mediated by macrophages, lymphocytes and dendritic cells Phagocytosis is a normal cellular process whereby the above cells (and neutrophils) engulf microbes and/or foreign material for intracellular for destruction Mediated by macrophages, lymphocytes and dendritic cells Phagocytosis is a normal cellular process whereby the above cells (and neutrophils) engulf microbes and/or foreign material for intracellular for destruction Microbes can hijack this process, avoiding intracellular digestion in two main ways Block fusion of the phagosome with lysosomes- TB Block actions of lysosomal enzymes- Johne’s disease

Answer 834

Ziehl-Neelsen - Mycobacteria Silver stain - Leptospirosis

Answer 835

Actinomyces Yersinia

Answer 836

Bacterial pathogenicity (ability to cause disease) is controlled by virulence factors Virulence factors of bacteria are typically glycolipids or glycoproteins encoded by genes Variably enable Motility – flagella Adhesion – adhesins Invasion – invasins Phagocyte resistance – biofilms and capsules Phagocyte destruction – toxins Tissue destruction – enzymes Inhibition of phagolysosomes – antioxidants Nutrition – siderophores – iron accumulation Some are expressed on the bacterial surface and can be used to type the bacteria See E.coli slides in large intestine lecture and later

Answer 837

Some bacteria form a polysaccharide matrix that confers a protective extracellular environment Staph aureus and UPEC Resists antimicrobials

Answer 838

Typically G-ve but some G+ve bacteria (and fungi) have capsules Enables attachment and nutrition, and evades phagocytosis

Answer 839

Attachment occurs when membrane proteins called adhesins, bind to receptors on cell membranes. Attachment can be a specific ligand-receptor interaction - a protein on the bacterium binds to a receptor on a host target cell. LPS Other bacteria utilize extensions of their cell membranes - fimbriae or pili to bind to cells. Fimbriae and pili bind to receptors on microvilli of the glycocalyx or in the mucus layer of epithelial cells. Fimbriae and pili may also inhibit phagocytosis.

Answer 840

stands for lipopolysaccharide Major component of gram-negative bacteria wall Referred to as O-antigen Virulence factor Stabilises membrane and resists chemical attack Adhesion and internalisation Brucella abortus Cardoso, Patrícia Gomes, et al. "Brucella spp noncanonical LPS: structure, biosynthesis, and interaction with host immune system. It is and endotoxin Released when G-ve bacteria die Stimulates practically all “arms” of the immune system AND coagulation

Answer 841

Exotoxins are actively produced by living G+ve bacteria Exotoxins work in four main ways Direct cytolysis Clostridium perfringens Pore-forming Staph aureus Inhibition of protein synthesis Corynebacterium Inhibition of ion pumps ETEC E coli

Answer 842

toxin released by dead G+ve bacteria

Answer 843

such as LPS are released from dead G-ve bacteria

Answer 844

Enterotoxigenic (ETEC)- Virulence factors: Attachment via fimbriae – F5 (K99), F41; F42, F165, F17, F18; F4 (K88), F6. Heat-labile (LT) and heat- stable toxins (ST), acting locally to alter secretion/absorption of electrolytes and water. Enteropathogenic (EPEC)- Virulence factors: Intimin - loosening of tight-junctions between enterocytes. Enterohaemorrhagic (EHEC) Virulence factors: Cytotoxic Shiga-/Vero- toxin Pathogenesis and pathophysiology: Non-structural alterations in cell membrane electrolyte and fluid transport (ETEC) Secretory diarrhoea Villus atrophy (EPEC) Coagulative necrosis (EHEC) Haemorrhagic diarrhoea

Answer 845

Bacterium exists as resistant endospores in environment and as vegetative forms Unknown mechanisms of adhesion, colonisation and infection Virulence factors Capsule: poly-D-glutamic acid (non-toxic) – prevents killing and digestion, antibody attachment and phagocytosis Toxins: 3 exotoxins acting together to cause cell death Protective antigen – creates a pore in cell membrane allowing entry of remaining toxins, oedema and lethal factor Inside cells protective antigen + oedema factor  oedema toxin protective antigen + lethal factor  lethal toxin Pathogenesis and pathophysiology: Oedema toxin disrupts electrolyte/water transport systems resulting in oedema Lethal toxin causes cytokine production which act to cause cell death especially of macrophages and capillary endothelial cells)

Answer 846

Bordetella bronchiseptica and Pasteurella multocida Bordetella phase Virulence factor: Dermonecrotic toxin (DNT) Pasteurella phase Virulence factor Pasteurella multocida toxin (PMT) Pathogenesis and pathophysiology: DNT Kills epithelial cells allowing access of PMT to submucosa PMT Increases osteoclasts and inhibits osteoblasts-> turbinate atrophy

Answer 847

C. perfringens is classified into 5 major types (A, B, C, D, and E), based on the production of 4 major lethal toxins: Type A produces alpha toxin Type B produces alpha toxin, beta toxin, and epsilon toxin Type C produces alpha toxin and beta toxin Type D produces alpha toxin and epsilon toxin Type E produces alpha toxin and iota toxin Alpha toxin (CPA): phospholipase C Gas gangrene, canine haemorrhagic diarrhoea, ferret gastroenteritis Epsilon toxin (ETX): Pore forming in enterocytes and endothelial cells Pulpy kidney

Answer 848

Mycobacterial species are the classic example of this method of pathogenicity and this is a key reason why mycobacterial infections result in multifocal chronic lesions Depending on the species, Mycobacteria can resist phagocyte killing in both ways Blocking fusion of phagosome with lysosome Blocking actions of lysosomal enzymes This inability to rid the bacteria results in the creation of pyogranulomas

Answer 849

Immunity against viruses involves interferon interferon-induced apoptosis of infected cells Interferon blocking viral replications

Answer 850

Viruses are often relatively specific for which cells they infect This is referred to as tissue tropism Mechanism is that viruses bind to cells via ligand-receptor interactions Other example would be Listeria (bacteria) having tropism for the brain as uses catecholamines as a food source Some viruses require a specific receptor and a co-receptor SARS Some viruses are pan-tropic in that they can infect many cells Canine distemper virus Cells that allow entry of viruses are called susceptible cells Cells that allow replication are called permissive cells Permissive cells are generally killed by lysis when the virus leaves the cell

Answer 851

The ability to change their antigen expression is core to the virulence of viruses Effectively the immune system has to relearn the new antigens Two main ways this occurs Antigenic shift Antigenic drift

Answer 852

Lungs – haematogenous, interstitial lesions Liver – random necrosis

Answer 853

Cell enlargement – syncytia versus ballooning, and viral inclusion bodies

Answer 854

Virulence factors Viral vascular endothelial growth factor (VEGF) stimulates capillary proliferation, induces vascular permeability, and enhances epithelial proliferation Orf virus cytokine IL-10 orthologue IL-10 suppresses recruitment and activation of neutrophils, monocytes and lymphocytes Orf virus interferon resistance gene (OVIFNR) inhibits IFN ORFV can initiate apoptosis in antigen producing cells and inhibit Bcl-2 to prevent apoptosis of virus infected cells

Answer 855

Rotavirus directly damages enterocytes-> villus atrophy -> malabsorption and osmotic diarrhoea And viral proteins and inflammation affect the enterochromaffin cells and enteric nervous system respectively-> secretory diarrhoea and increased motility Rotavirus is also rare in that it produces a toxin NSP4-> secretory diarrhoea

Answer 856

Replicate by inserting a DNA copy of their RNA genome into host DNA Lentiviruses Maedi-Visna FIV HIV/SIV Oncoretroviruses FeLV Mouse mammary tumour virus Avian leukosis virus (ALV) and reticuloendotheliosis virus (REV) Bovine leukaemia virus Enzootic nasal tumour and Jaagsiekte sheep retrovirus Viral genes pol – encodes reverse transcriptase and other enzymes gag – encodes for group-specific nucleocapsid & matrix glycoproteins; detected by antibody-based tests env – encodes for surface glycoprotein that mediates receptor binding and virus entry into cells; target for neutralizing antibody Lentiviruses Infect monocytes/macrophages or CD4 lymphocytes Immunosuppression (FIV and SIV) Progressive pneumonia (MV) Oncoretroviruses Stimulate neoplastic transformation in host cells Typically lymphoma Jaagiekte causes pulmonary carcinomas of type 2 pneumonocytes

Answer 857

Bovine leukaemia virus Notifiable Avian leukosis FIV The risk for developing lymphoma in FIV-infected cats is fivefold to sixfold higher than in uninfected cats Intestinal B-cell lymphoma FeLV Lymphoma is increased 60-fold in infected cats Commonly results in T-cell mediastinal/thymic lymphoma Vaccination has markedly reduced this

Answer 858

Coccidia come in two families- the Eimeriidae (Eimeria, Isospora and Cryptosporidium) and the Sarcocystidae (Toxoplasma, Neospora and Sarcocystis). The general life cycle of both is ingestion of oocysts from which sporozoites emerge (excystation) and invade enterocytes → multiple rounds of asexual merogony/schizogony in enterocytes, formation of sexual stages (gamonts) that fuse to form oocysts, passed in faeces. Eimeriidae are only found in the gut. Sarcocystidae may leave the gut and form cysts in tissues (bradyzoites). In some circumstances these can release fast-dividing tachyzoites that cause necrosis and inflammation (e.g. Toxoplasma, Neospora, Sarcocystis) but the gut cycle is vital for sexual reproduction. Not all Eimeria spp are pathogenic Therefore faecal oocyst counts can be difficult to interpret See other lectures/dry labs All pathogenic coccidia at some point damage enterocytes Enterocytes are damaged when mature schizonts rupture and release merozoites Malabsorption due to villus atrophy Exudative enteritis and haemorrhagic typhlitis due to epithelial erosion and ulceration In alpacas, infection with E. macusaniensis can predispose to other infections such as clostridia Impair intestinal barrier and later permeability-> diarrhoea Cryptosporidium may produce an enterotoxin resulting in secretory diarrhoea Sarcocystidae can have a relatively benign existence outside of the GIT Sarcocystis cysts seen frequently in the muscle, including heart, of ruminants with noassociated inflammation Disease occurs when Cysts rupture Dead-end hosts and/or nervous system infected S. neurona in horses -> infection of spinal cord Toxoplasma and Neospora in the brain of dogs Neospora is also an important cause of abortion in cattle

Answer 859

Two major forms of trypanosomiasis: American trypanosomiasis: Trypanosoma cruzi African trypanosomiasis: T. congolense, T. vivax, T. brucei brucei Vector-borne Four morphologic forms: Amastigotes (intracellular form): Only form which lacks flagellum; multiplies within mammalian cells – only T.cruzi Trypomastigotes (blood form): Infective form which does not multiply, extracellular; flagellated with characteristic undulating membrane Trypanosomes are interesting in that they are seen freely within the blood of affected animals Epimastigotes (intermediate form); found in vectors and multiplies in the midgut Promastigotes: Rapidly dividing stage Virulence factors Two proteins on the surface of cruzi are involved in its entry into macrophages and other host cells Trans-sialidase: Removes host cell sialic residues and transfers them to a parasite surface protein (Ssp-3), which binds to host cells Penetrin: Binds extracellular matrix proteins, heparin, heparin sulfate, and collagen and mediates parasite invasion into host cells Intramacrophage survival due to rapid movement from lysosome to the cytosol Neuraminidase: Removes sialic acids from host proteins lining the lysosomes and destabilizes this organelle Hemolysins: Lysosomal acid pH stimulates parasite release of hemolysins, which form pores in and disrupt lysosomal membranes Immune evasion Antigenic variation in membrane surface glycoproteins = variant surface glycoprotein (VSG), Forces the host to constantly redevelop their humoral response and makes making a vaccine virtually impossible Chronically T. cruzi causes myocarditis T. evansi and others can cause neurological signs due to inflammation in the brain (meningoencephalitis) How they cross the BBB is unknown See SVMPH lecture by Prof Helen Price for more

Answer 860

Fungi exist in the environment and as a normal commensals as yeasts or molds (hyphae) Most pathogenic fungi have both forms in their life cycle= dimorphic Can be classed as superficial Candida Aspergillus Or systemic Histoplasmosis, blastomycosis Coccidiomycosis, cryptococcus Angio-invasive fungi Ruminal acidosis Fusarium, Absdia, Rhizopus and Mucor spp Virulence factors: Yeasts have a capsule In cryptococcus it is very thick Polysaccharide Virtually impossible to effectively phagocytose Some contain melanin which is an antioxidant inhibits lysosomal digestion if is phagocytosed Surface antigens Sequester humoral immunity Constantly shed As is typical of pathogens that resist phagocytosis, they cause a chronic inflammatory reaction with granulomatous inflammation

Answer 861

Conidia are inhaled and deposited in mucus layer Normally phagocytosed and killed: if phagocytosis is disrupted (immunosuppresion) then conidia germinate into hyphae and both secrete enzymes that damage the epithelium and expose the basal lamina for easy colonisation and invasion. Virulence factors: Gliotoxin - anti-inflammatory, apoptosis of phagocytes Fumagillin and hevolic acid – antibiotics Melanin - antioxidant Grossly, cause grey/black pseudomembranous rhinitis/airways in dogs; may invade underlying bone (necrosis) and also cause granulomas around airways. Cattle: lungs, placenta, udder. Horse: guttural pouch. Cats: Lungs. Spread systemically by leukocyte trafficking or by angioinvasion - rare

Answer 862

Helminths are highly prevalent parasites. They infect some 2 billion people, nearly one third of the human population. In animals they are omnipresent. Helminths establish in a range of tissue and particularly intestinal niches, producing eggs or larvae to infect new hosts. Can in some cases form stable chronic infections for potentially years. Their extraordinary prevalence and ability to remain in the body whilst eliciting typically a minimal response, neutralizing immune pathways that would otherwise expel them indicate that they are potentially immunosuppressive and certainly immunomodulatory. In so doing, they also dampen responses to unrelated bystander specificities, such as allergens and autoantigens, in a manner that may actually benefit the host = hygiene hypothesis, but can potentially reduce vaccination efficacy of unrelated disease. One of the most well studied is Taenia solium Patients have increased IL-10 levels Decreased TH1 and TH2 cytokine levels increased Tregs

Answer 863

Chondrodysplasia Signalment: Dexters and other miniatures Pathogenesis: 2 different mutations in the aggrecan (ACAN) gene Gross: Carried to full term but are usually aborted before the seventh month of gestation Aborted calves may or may not have hair and are much smaller than normal Extremely short limbs, usually rotated Short, domed head with protruding mandible Cleft palate; and a large ventral abdominal hernia Tongue is normal size so protrudes from mouth Histo: Lack distinct growth plates. Physeal cartilage consists of densely packed chondrocytes showing no orderly arrangement into columns, and a fibrillar eosinophilic intercellular matrix.

Answer 864

Chondrodysplasia Signalment: Suffolk and Hampshire sheep Pathogenesis: Autosomal recessive FGFR3 Gross: Disproportionately long limbs and neck, shallow body, scoliosis and/or kyphosis of the thoracic spine, concave sternum and other sternal deformities Valgus deformity of the forelimbs below the carpus creating a knock-kneed appearance Histo abnormal development of ossification centers in bones that develop by endochondral ossification

Answer 865

Chondrodysplasia Signalment: Suffolk and Hampshire sheep Pathogenesis: Autosomal recessive FGFR3 Gross: Disproportionately long limbs and neck, shallow body, scoliosis and/or kyphosis of the thoracic spine, concave sternum and other sternal deformities Valgus deformity of the forelimbs below the carpus creating a knock-kneed appearance Histo abnormal development of ossification centers in bones that develop by endochondral ossification

Answer 866

a condition characterized by faulty development of cartilage and growth of bone in the ossification centers of bones of nonmembranous origin bulldog calves spider lamb scotish folds and american curls

Answer 867

Signalment Scottish fold and American Curl Pathogenesis: Autosomal dominant fd (fold-eared) gene Gross: Irregularity in the size and shape of tarsal, carpal, metatarsal, and metacarpal bones; phalanges; and caudal vertebrae. Secondary degenerative arthropathy Histo defective endochondral ossification in physes and beneath articular cartilage

Answer 868

Physeal dysplasia in cats (atraumatic slipped capital femoral epiphysis) Signalment: male and overweight Siamese and Maine Coon breeds over-represented typically young (2-4 years), but older than the age of expected physeal closure (7-9 months) Pathogenesis: Unknown Physeal dysplasia is seen in all growth plates but only the proximal femoral physis fractures, presumably because of the shear forces at that site Gross: Head of femur avulsed Histo dysplastic growth plates characterized by disorganized clusters of chondrocytes surrounded by abundant matrix

Answer 869

Signalment One of the most frequently observed inherited connective tissue disorders of humans, but occurs rarely in domestic animals Holstein-Friesian, Charolais, Angus Romney lambs Beagles, Goldies, Daxxies Pathogenesis: Mutations in either the COL1A1 (goldie) or COL1A2 (beagle) genes that code for the α1 and α2 collagen chains, respectively. The disease in Dachshunds has autosomal recessive inheritance and is caused by a missense mutation in the SERPINH1 gene, which codes for an essential collagen chaperone, HSP47 Gross: Unable to stand because of marked hypermobility of joints Dentinogenesis imperfecta Bones are essentially normal in shape but are extremely brittle Histo: Osteoblast numbers and activity vary Calcified cartilage spicules in the primary spongiosa are lined by only a thin layer of basophilic bone matrix Little osteoclastic resorption or realignment of trabeculae. Deeper in the secondary spongiosa trabeculae may be lined by woven bone.

Answer 870

Rickets, osteomalacia, fibrous osteodystrophy, and osteoporosis Distinct morphologic entities with characteristic pathogenesis and lesions, but can occur in combination in the same individual Further terminology: Osteopenia = increased radiolucency of bone, but makes no inference as to its quality. Includes osteoporosis (less bone), and osteomalacia, fibrous osteodystrophy, and osteogenesis imperfecta (less bone and abnormal quality/consistency) Their cause can vary between species E.g. calcium deficiency in sheep results in osteoporosis, but in a rapidly growing pig, causes fibrous osteodystrophy. Pathogenesis Vitamin D/phosphorus/calcium deficiencies/imbalances metabolic bone diseases seldom result from a deficiency of a single dietary nutrient. More often, there is either a deficiency of several nutrients or a dietary imbalance in the ratio of calcium to phosphorus Signalment Horses fed bran-based diet Fibrous osteodystrophy Physiological due to fracture/paraplegia First lactation dairy cows Copper deficient farm animals Malabsorption syndromes – PEG in growing lambs, dogs with IBD Rapidly growing animals with deficient diets

Answer 871

Metabolic/nutritional osteodystrophies Rickets (growing animals) and osteomalacia (older animals) Same thing Defective endochondrial ossification rickets in growing therefore issues with growth plates Pathogenesis Vitamin D deficiency (nutritional or genetic) Phosphorus deficiency Dietary phosphorus deficiency is virtually impossible in carnivores because of the high levels of phosphorus normally present in their rations. Excess dietary phosphorus, results in nutritional secondary hyperparathyroidism (resulting in rickets) and fibrous osteodystrophy commonly in puppies and kittens Gross Most prominent at sites of rapid growth, including metaphyseal and epiphyseal regions of long bones and costochondral junctions of the large middle ribs. Enlargement of costochondral junctions is a classic feature of the human disease and is referred to as the “rachitic rosary.” Histo Persistence of hypertrophic chondrocytes at sites of endochondral ossification, both at physes and beneath articular cartilage, is the hallmark of rickets in histologic preparations The lesions of osteomalacia are similar to those of rickets but because they occur in adult animals, growth plates are not involved excessive deposition of matrix where mechanical stimuli are strongest, such as at insertions of tendons and fascia trabeculae are reduced in size and number, and the cortices are thin and porous. Osteoid covers the trabeculae and lines the expanded Haversian canals. Localized accumulations of osteoid occur at sites of mechanical stress

Answer 872

Metabolic/nutritional osteodystrophies Pathogenesis Persistent elevation of parathyroid hormone Primary or secondary hyperparathyroidism Primary - persistent hypercalcemia and hypophosphatemia Secondary - calcium concentrations are usually either normal or slightly decreased, and depending on the cause, plasma phosphorus concentrations are either normal or increased Secondary hyperparathyroidism is a much more common cause of fibrous osteodystrophy in animals than primary hyperparathyroidism and may stem from either chronic renal disease or dietary imbalance of calcium and phosphorus. PTH secretion is stimulated by reduction in plasma ionized calcium, whatever the cause, and if the stimulus persists, then generalized bone resorption results Horses and goats – high bran/concentrate diets Carnivores – meat and offal only diets Gross Bilateral enlargement of the bones of the skull, affecting both the maxillae and mandibles Histo 3 key features osteoclastic bone resorption fibrosis osteoblastic deposition of new woven bone Lesions may vary with state of disease and specific bones involved.

Answer 873

Metabolic/nutritional osteodystrophies Pathogenesis Persistent elevation of parathyroid hormone Primary or secondary hyperparathyroidism Primary - persistent hypercalcemia and hypophosphatemia Secondary - calcium concentrations are usually either normal or slightly decreased, and depending on the cause, plasma phosphorus concentrations are either normal or increased Secondary hyperparathyroidism is a much more common cause of fibrous osteodystrophy in animals than primary hyperparathyroidism and may stem from either chronic renal disease or dietary imbalance of calcium and phosphorus. PTH secretion is stimulated by reduction in plasma ionized calcium, whatever the cause, and if the stimulus persists, then generalized bone resorption results Horses and goats – high bran/concentrate diets Carnivores – meat and offal only diets Gross Bilateral enlargement of the bones of the skull, affecting both the maxillae and mandibles Histo 3 key features osteoclastic bone resorption fibrosis osteoblastic deposition of new woven bone Lesions may vary with state of disease and specific bones involved.

Answer 874

Toxic osteodystrophies Signalment- Cats fed liver Pathogenesis Inhibits chondrocyte proliferation and reduces RNA and protein synthesis. Lysis of matrix may be the result of destabilization of lysosomal membrane Gross Osteophyte formation is the hallmark -> deforming cervical spondylosis Histo Physeal lesions - reduced chondrocyte proliferation and reduced size of hypertrophic chondrocytes, resulting in narrowing of growth plates. Osteoporosis- decreased numbers of osteoblasts and fewer, thinner osteoid seams

Answer 875

Toxic osteodystrophies Pathogenesis Impaired osteoclastic resorption Osteoclasts may contain acid-fast intranuclear inclusions Gross A band of sclerosis, referred to as a “lead line” or Histo Persistence of mineralized cartilage trabeculae in the metaphysis

Answer 876

Bacteria infect bone by 3 routes: hematogenous, local extension implantation. Hematogenous osteomyelitis is very common in animals, especially young horses and ruminants. >70% will also have septic arthritis (joint ill). During bacteraemia, there is a predilection for bacteria to localize to sites of active endochondral ossification within the metaphyses and epiphyses of long bones and vertebral bodies Some bacteria have a predilection for bone. Staphylococcus aureus, for example, can invade osteoblasts. Trueperella (Arcanobacterium) pyogenes is the most common causative organism in vertebral osteomyelitis in large animals, but a range of other bacteria may be involved. These include: Escherichia coli, Salmonella enterica serovar Typhimurium, staphylococci, streptococci, and Rhodococcus equi in foals; Fusobacterium necrophorum in calves; Mannheimia haemolytica, F. necrophorum, and staphylococci in sheep; and Erysipelothrix rhusiopathiae, staphylococci, and streptococci in pigs. In dogs, vertebral osteomyelitis has been linked to migration of plant material. In cats, bite wounds are the most likely route of infection. Lumpy jaw - Mandibular osteomyelitis in the cow Aetiology- Actinomyces bovis Gross “Honeycomb” appearance caused by pockets of inflammatory tissue surrounded by reactive bone. Histo: Colonies of A. bovis surrounded by characteristic brightly eosinophilic clubs of Splendore-Hoeppli material and suspended in a dense neutrophilic exudate. Atrophic rhinitis of pigs- Aetiology mediated by bacterial toxins produced by Pasteurella multocida and Bordetella bronchiseptica. Pathogenesis These toxins inhibit osteoblast differentiation and stimulate osteoclast activity, resulting in bone loss

Answer 877

Some viruses directly infect osteoclasts: canine distemper bovine viral diarrhoea Resulting in an acquired impairment of osteoclastic resorption of bone during growth and continued endochondral ossification resulting in: A dense band of grossly appreciable sclerotic bone at the metaphysis of developing bone Often directly subjacent to the growth plate Referred to as a growth retardation lattice Resulting in an acquired impairment of osteoclastic resorption of bone during growth and continued endochondral ossification resulting in: A dense band of grossly appreciable sclerotic bone at the metaphysis of developing bone Often directly subjacent to the growth plate Referred to as a growth retardation lattice

Answer 878

Legg-Calves-Perthes disease Signalment Westies 4-8m Pathogenesis Inherited as an autosomal recessive trait Ischaemia Delayed incorporation of vessels supplying the femoral head into protective fibro-osseous canals? Gross Fracture and collapse of the necrotic trabecular bone and flattening of the femoral head Histo Subchondral epiphyseal osteonecrosis

Answer 879

An avulsion fracture occurs when there is excessive trauma at sites of ligamentous or tendinous insertions and a fragment of bone is torn away

Answer 880

Microscopic fractures of individual trabeculae, or localized segments of cortical bone, also occur and are referred to as microfractures. Displacement of the bone ends are referred to as infractions.

Answer 881

Inflammation Soft callus formation Hard callus formation Remodelling

Answer 882

Histologic appearance depends on the phase of bone repair and alignment or not of the fracture ends Histological appearance will vary but is typically defined as: cartilage undergoing endochondral ossification composed of tightly packed chondrocytes in a basophilic matrix with densely packed fibroblasts and collagen fibres Additionally may see bone fracture blood clot necrotic bone periosteal and endosteal proliferation high numbers of osteoblasts The key microscopic feature of reactive bone formation is that of well-ordered maturation.

Answer 883

beningn- Osteoma Chondroma Fibroma Multilobular tumour of bone malignant- Osteosarcoma Chondrosarcoma Fibrosarcoma

Answer 884

Cell of origin unclear Mesenchymal stem cells Osteoblast Osteocyte Common in dogs and cats and the most common bone tumour (95%. Typically, appendicular/long bones (away from the elbow, towards the knee), but also ribs and extra-axial (mammary). Aggressive, painful and quick to metastasise (lungs). Gross Grey-white gross and contain variable amounts of mineralized bone. Large, pale areas surrounded by zones of haemorrhage (areas of infarction). Neoplastic tissue will fill the medullary cavity Does not penetrate articular cartilage and therefore does not invade the joint space. Cortical bone is usually destroyed Neoplastic cells penetrate and undermine the periosteum and can extend outwardly as an irregular lobulated mass (“sunburst” pattern on radiograph) Destruction of cortical bone results in pathological fractures Histo Unencapsulated, infiltrative, densely cellular neoplasm composed of spindle cells Production of varying amounts of eosinophilic homogeneous to fibrillar matrix (osteoid) and reactive (nonneoplastic) periosteal bone Fibrovascular matrix. Moderate to brisk mitotic rate and some anisokaryosis and anisocytosis. Occasional multinucleated giant cells that resemble osteoclasts.

Answer 885

Fibrosarcomas of the appendicular skeleton are much less common than osteosarcomas That said, fibrosarcomas are the third most common tumour of cats these are typically soft tissue sarcomas, and injection site-associated (see oncology next year) Fibrosarcomas also relatively common in dogs and cats associated with the mouth See oral pathology lecture Histo appearance is typical of a mesenchymal tumour Fusiform cells and nuclei

Answer 886

Hypertrophic osteopathy- Marie’s Disease Secondary to (typically) intra-thoracic pathology but also reported in association with bladder tumours and hyperadrenocorticism Unclear pathogenesis Characterized by progressive, often bilateral, periosteal, new bone formation of the distal limbs Bone cysts- Most common in the horse Aneurysmal, simple (unicameral) and subchondral Also dentigerous cysts Osteochondromas (cartilaginous exostoses)

Answer 887

Mammary, liver, lung and prostatic carcinomas preferentially metastasise to bone. Ribs, vertebrae and proximal long bones in dogs Clinically silent pulmonary carcinomas in cats metastasize to the third phalanx, causing destruction of the nail bed epithelium (“feline lung-digit syndrome”).

Answer 888

Pathogenesis Denervation- Types 1+2 Disuse- Predominantly Type 2 Endocrine- Predominantly Type 2 Malnutrition - Predominantly Type 2 Congenital- Predominantly Type 1

Answer 889

Predominantly reported in dogs, but also cattle Pathogenesis: Canine Masticatory myositis: Canine masticatory muscles have a unique myosin isoform (2M) Various bacterial infections may lead to misdirected antibodies against type 2M -> muscle fibre necrosis Gross: Bilateral severe masticatory muscle wastage Histo: Multifocoal polyphasic myofiber degerenation and necrosis Lymphocytes predominate with various eosinophils Localised extraocular form in Goldies Localised tongue form in Japanese Welsh corgis Polymyositis in dogs is typically associated with severe underlying systemic disease such as lupus, lymphoma and thymoma Feline disease associated with FIV Cattle form is eosinophil rich and may be associated with sarcocystis

Answer 890

Wooden tongue Cattle Actinobacillus lignieresii Blackleg Clostridium chauvoei Necrosis, gas formation

Answer 891

White muscle disease Pathogenesis- Vit E/selenium deficiency

Answer 892

Porcine stress syndrome (PSS) or malignant hyperthermia Pathogenesis Defective calcium channel Gross- Pale soft exudative pork Capture myopathy Exertional rhabdomyolysis Mild will just see increased CK/AST/LDH Myoglobin is toxic to renal tubular cells Myoglobinuria Renal failure in severe cases

Answer 893

Double muscling Pathogenesis Defect in myostatin Muscles are hyperplastic and hypertrophic Muscular dystrophy Pathogenesis Defect in dystrophin X-linked Splay-leg Hyperkalaemic periodic paralysis Pathogenesis Defect in sodium channel Polysaccharide storage myopathy Pathogenesis Defect in glycogen handling

Answer 894

Neutrophils Macrophages Dendritic cells (B-cells)

Answer 895

Component of serum Roles: Chemotactic Increase vascular permeability Opsonisation Formation of membrane attack complex (MAC)

Answer 896

Proteins, peptides and glycoproteins Typically only produced by leukocytes, but also fibroblasts and endothelial cells Interleukins (IL-), interferons (IFN-), tumour necrosis factor (TNF) Modulate functional expression of inflammatory cells in acute inflammatory response Also major roles in haematopoiesis and adaptive immunity Grouped into: Hematopoietic growth factors – IL-3, G-CSF, GM-CSF +/- IL-9, IL-11 and stem cell factor Inflammatory mediators – including acute phase reactants and natural immunity, IL-1, IL-6, TNF α and β Chemotactic – IL-8 T lymphocyte proliferation, activation and differentiation – IL-2, 4, 5, 7, 9, 10, 12, and 17 through 29 Biochemically, cytokines divided into type I or type II Type I – 4 α helices Type II - 6 α helices Variety of stimuli invoke cytokine expression and wide range of receptors Chemokines: Smaller Type of cytokine that primarily promote leukocyte chemotaxis and migration across capillaries and venules Produced by all nucleated cells

Answer 897

Key antigen presenting cells (APCs) Monocyte-macrophage lineage/ monocyte phagocytic system special type of immune cell that is found in tissues, such as the skin, and boosts immune responses by showing antigens on its surface to other cells of the immune system. A dendritic cell is a type of phagocyte and a type of antigen-presenting cell (APC).

Answer 898

T helper-cells (CD4) can differentiate into different functions Th1, Th2, Th17 and T-regs T-cells can differentiate into different functions TH1, TH2 and T-regs TH1 lymphocytes are activated by IL-12 and IL-18 and produce primarily IL-2, IFN-γ, and TNF-β to direct a cell-mediated immune response. TH2 lymphocytes are activated by IL-4 and produce primarily IL-3, IL-4, IL-5, IL-6, IL-10, and IL-13 to direct a humoral immune response.

Answer 899

Immunity to feline infectious peritonitis (FIP), when it occurs, is largely cell-mediated Production of antibodies is counterproductive Antibodies enhance the uptake and replication of FIPVs in macrophages Also contribute to a type III hypersensitivity (antibody-mediated) vasculitis Reason why the vaccination made the disease worse It is also assumed that much of the pathology occurring in FIP is associated with how macrophages respond to viral infection and how the immune system of the host responds to the infected cells. The effusive form of FIP results from a failure to mount T-cell immunity in the face of a vigorous B cell response. At the opposite extreme, cats that resist disease presumably mount a vigorous cell-mediated immune response that is able to overcome any negative effects of antibodies. Cats with the dry form of FIP represent an intermediate state involving a cellular response that is partially effective in containing the virus to a relatively small number of macrophages in a few focal sites within specific target organs. The two forms of FIP are somewhat interchangeable; when it has been observed in experimental infection, the dry form always follows a brief bout of effusive disease. In the terminal stages of naturally occurring dry FIP, immunity can completely collapse and the disease reverts to a more effusive form.

Answer 900

Under appropriate conditions, B-cells mature to plasma cells Plasma cells produce immunoglobulins Five different classes of antibodies (in mammals): IgG IgM IgA IgE IgD The class of immunoglobulin secreted by B cells and plasma cells depends on their location. Cells located in lymphoid organs within the body secrete IgM and IgG, whereas cells located on mucosal surfaces mainly secrete IgA and/or IgE. IgG is the most abundant immunoglobulin found in the bloodstream and clostrum. IgM is usually confined to the bloodstream because it is a very large molecule with much more antigen binding capacity compared with the smaller IgG, which can easily go into interstitial spaces. IgA is produced by B cells and plasma cells located on mucosal surfaces. Most abundant in milk. IgE is produced locally by plasma cells and then binds with a very high affinity to tissue mast cells. Involved in allergy (see later).

Answer 901

Occurs from dam to neonate via colostrum. IgG. Enterocyte only able to take up IgG in first 24-36hours of life. Suboptimal transfer occurs is approximately 35% of dairy calves. Failure of passive transfer (FPT) Predisposes neonate to systemic infections Joint ill Can be measured in two ways Indirect Serum total protein Zinc sulphate turbidity test GGT levels Direct ELISA (snap test) - foals

Answer 902

Primary lymphoid organs Antigen-independent formation of lymphocytes Thymus Bursa of Fabricius Bone marrow Peyer’s patches (in ruminants) Foetal liver Secondary lymphoid organs Antigen-dependent maturation of lymphocytes Spleen Tonsil Peyer’s patches Lymph nodes Tertiary MALT/GALT/BALT Sampling of pathogens at epithelial surfaces

Answer 903

Immunodeficiency can be defined as a relative or absolute inability of the immune system to protect the host from infection Primary or secondary Primary- Genetic deficiency in a component of the immune system Secondary- Exogenous cause of defective immunity Infectious Radiation/chemotherapy Age-related Nutritional

Answer 904

SCID One of the best well known immunodeficiencies Family of genetic defects- X-linked Autosomal recessive Sporadic Affects adaptive immunity T or T and B - cell Deficiencies in both humoral and cellular mediated responses Horses Arabian Autosomal recessive Lymphopaenia and agammaglobulinaemia Death due to secondary infections In mice this is selectively bred for for experimental purposes Gross pathology includes marked thymic hypoplasia

Answer 905

Defective ability to release intracellular granules and reduced ADP Affects All granulocytes Melanocytes Platelets

Answer 906

Humans, dogs (Irish Setters) and cattle (Holsteins) CD18 deficiency High numbers of neutrophils circulating, but cannot migrate through the endothelium

Answer 907

Foal immunodeficiency syndrome (FIS), previously known as Fell Pony syndrome Autosomal recessive Severe anaemia and B cell lymphopenia

Answer 908

Grey collie syndrome/cyclic haematopoiesis Autosomal recessive Every 10-12 days the neutrophil count drops dramatically Death before 6 months

Answer 909

Infections primarily cause immunodeficiency in three ways Destruction of a physical barrier Consumption of immune factors Direct infection/destruction of immune cells and/or tissues Canine parvovirus and feline panleukopaenia Examples of all three Apoptosis of enterocytes Destruction of the gut/bloodstream barrier Virulent Lymphocyte and/or precursor infection Resulting in diarrhoea, secondary bacterial infections, panleukopaenia Inflammation and infection can result in autoimmunity in 5 keys ways Upregulated expression of costimulators on APCs that present self-antigens Molecular mimicry Some infectious agents express antigens that have the same amino acid sequences as self-antigens, leading to activation of self-lymphocytes Polyclonal B cell activation Tissue injury Causes self-antigen release. These antigens are may also be altered by injury Stimulate production of cytokines NB: infection can also protect against allergy/autoimmune disease. See POP Infection – protozoa, fungi and helminths lecture

Answer 910

Definition Altered and injurious immune reactivity to a specific antigen in a sensitised host General features: Elicited by antigens endogenous or exogenous microbial and nonmicrobial Imbalance of effector and control mechanisms Often associated with particular susceptibility genes Tissue injury mechanism same in hypersensitivity as in normal defence effector mechanisms Just poorly controlled, excessive or misdirected Sensitisation and effector phases allergic cytotoxic immune complex delayed

Answer 911

“Allergy” Rapid reaction in a previously sensitised individual triggered by binding of an environmental antigen to IgE antibody on mast cell surface Most caused by excessive Th2 responses; stimulate IgE production and promote inflammation Systemic (injection, ingestion) or local reaction Two phases: 1) Immediate (mins  hours) – vasodilation, vascular leakage, smooth muscle spasm, gland secretion 2) Late (2-24 hours  days) – tissue infiltration with eosinophils, neutrophils, basophils, monocytes, CD4+ T cells AND tissue destruction (mucosal epithelial) Mediators of Immediate Hypersensitivity Pre-formed (primary) mediators stored in granules Vasoactive amines – e.g. histamine  smooth muscle contraction, ↑vascular permeability, ↑mucus (nasal, gastric, bronchial) Enzymes – e.g. neutral proteases (chymase, tryptase), acid hydrolases. Cause tissue damage and lead to generation of kinins and activate complement components (C3a) Proteoglycans – e.g. heparin and chondroitin sulfate. Package and store the amines in granules Lipid mediators - membrane phospholipids  arachidonic acid  leukotrienes (5-lipoxygenase), prostaglandins (COX) Leukotrienes – C4, D4 (vasoactive) and B4 (neutrophil chemotactic) Prostaglandin D2 Platelet-activating factor Cytokines – many Leukocyte recruitment - TNF, IL-1, chemokines Amplify Th2 response – IL-4 Histamine-releasing factors Development of Allergies Susceptibility genetically determined= “atopy” Several genes Higher serum IgE, more IL-4-producing Th2 cells Environmental factors – pollutants, viral infections, bacterial skin infections 20-30% of immediate reactions triggered by non-antigenic stimuli e.g. temperature extremes, exercise, and do not involve IgE or Th2 cells = “nonatopic allergy” Systemic Anaphylaxis Vascular shock, oedema, difficulty breathing Local Immediate Hypersensitivity Reactions Reaction to e.g. pollen, animal dander, food Cause urticarial, allergic rhinitis, bronchial asthma, etc. Acute allergic reaction (local hypersensitivity) defined as an acute onset of illness and evidence of generalized mediator release restricted to cutaneous findings alone erythema, pruritis, urticaria, or angioedema without any other systemic signs. Systemic (generalized) hypersensitivity reactions classified by the severity of the systemic reaction based on a grading system Mild skin/mucosal tissue without involvement of other organs but having some indication of a generalized component (eg, fever) Moderate systemic involving 2 or more organ systems, animals are normotensive and without evidence of neurologic compromise. Severe evidence of neurologic compromise (collapse or syncope) or hypotension Moderate and severe systemic hypersensitivity reactions are classified as anaphylaxis In human medicine, serum mast cell tryptase can be measured Post mortem findings Acute cardiogenic failure Marked diffuse vascular congestion of lungs, liver, intestine Marked diffuse alveolar oedema of the lungs Histo Moderate hydropic degeneration of centrolobular to midzonal hepatocytes In humans, histopathology of lungs will show increased numbers of mast cells

Answer 912

Part of the innate immune system A granulocyte Contains cytoplasmic granules Mast cells are normally distributed throughout connective tissue adjacent to blood vessels and lymphatics within the skin and mucosa When exposed to inciting agent and IgE, degranulate to release histamine Histamine is a vasoactive amine-> vasodilation and increased permeability of vessels

Answer 913

Antibodies react with antigens on cell surfaces or in ECM  destroy these cells, trigger inflammation or interfere with normal function Antigens endogenous or exogenous (drugs, microbial protein) IgM and IgG Occur within hours after exposure in sensitized host Three mechanisms: Opsonization and Phagocytosis - IMHA Inflammation- Glomerulonephritis(not all), Vascular issues and rejection in organ grafts Dysfunction- Myasthenia gravis

Answer 914

Antigen-antibody complexes Inflammation at site of deposition- Typically vascular Examples- Blue-eye in canine adenovirus (hepatitis) FIP

Answer 915

CD4+ T cell-Mediated Inflammation cytokines produced by the T cells induce inflammation that may be chronic and destructive Delayed type hypersensitivity Th1 and Th17 cells contribute to organ-specific diseases in which inflammation is a prominent aspect of the pathology Th1 – activates macrophages Th17 – activates neutrophils Tuberculin skin reaction

Answer 916

Self tolerance = lack of responsiveness to own antigen Antigen receptors of lymphocytes are generated by somatic recombination of genes in a random fashion. Receptors recognising self antigens are constantly generated These self-recognising lymphocytes must be “taught” to not react to self antigens Occurs centrally or peripherally: Centrally- Thymus and bone marrow Peripherally- Anywhere there are APCs Occurs in four ways- Centrally T and B cells can be deleted (apoptosis) T-cells can also be delete peripherally Or T-cells can be pushed toward becoming T-regs Peripherally T and B cells can become anergic T-regs locally supress the immune response

Answer 917

Some sites do not communicate with blood/lymph: And/or have minimal MHC expression Examples: testes, eye & brain Because of this, the thymus does not need to “tell” lymphocytes not to react to them Therefore, if trauma or leakage of this tissues does expose them to the immune system, the immune response is typically marked and chronic- Examples: post-traumatic orchitis Conversely, it is difficult to elicit an immune response to antigens introduced into these sites More on the eye- Cells of iris and ciliary body also produce inhibitory cytokines Corneal endothelium and retina express practically no MHC class 1- Inability to activate cytotoxic T-cells

Answer 918

1. Defective tolerance Breakdown of the previously discussed self-tolerance mechanisms. Genetic – complex multigenic MHC alleles 2. Increased expression or persistence of self antigens or changes to self antigens These antigens undergo structural changes as a result of cellular stress or injury, or from enzymatic modifications. These changes lead to the display of antigenic epitopes that are not expressed normally. The immune system may not be tolerant to these epitopes. 3. Inflammation/infection The innate immune response creates a strong stimulus for subsequent activation of lymphocytes & generation of an adaptive immune response. Microbes or cell injury can induce inflammatory reactions that resemble the innate immune response, inducing autoimmune disease.

Answer 919

Lupus erythematosus occurs in two distinct forms in animals: Systemic lupus erythematous (SLE)- which affects multiple tissues, occasionally including the skin Cutaneous or discoid lupus erythematous (CLE/DLE)- lesions are localized to the skin. SLE: Recognized in mice, humans, non-human primates and various domestic animals. Pathogenesis- Loss of B- and T-cell tolerance to self-antigens Autoantibodies against a range of nuclear and cytoplasmic components of the cell, including histones, double-stranded DNA, nonhistone proteins bound to RNA, and nucleolar antigens. Incites a type 3 hypersensitivity reaction, but also type 2 and 4 depending on type Definitive cause unclear Pathophysiology- Systemic inflammation Autoantibodies and self-antigen complexes deposit within glomeruli, blood vessels, skin and joints, A wide spectrum of clinical presentations Affected patients may exhibit a combination of renal disease (glomerulonephritis, interstitial nephritis, vasculitis, and proteinuria), polyarthritis, skin lesions, hematologic disorders, respiratory, or neurologic dysfunction. In domestic animals, lupoid skin disorders, such as CLE, are most frequently seen in the dog, often localized to the nose: Gross lesions range from alopecia to scaling to ulcerative dermatitis Depigmentation of the nose is classic of DLE but not pathognomonic Histopathology is diagnostic Interface dermatitis

Answer 920

Fever Nonerosive polyarthritis - Characterised by exudation of neutrophils and fibrin into synovial membrane + perivascular cuffing by mononuclear cells Primarily affects intervertebral, carpal, tarsal, temporomandibular Glomerulonephritis- Deposition of immune complexes in glomerulus, blood vessels & basement membrane of renal tubules Persistent proteinuria (>0.5g/dL) Variable from slight mesangial alterations to diffuse proliferative lesions Mucocutaneous lesions Skin lesions: Non-specific in the dog Affects face, ears & digital extremities Erythema, ulceration & exfoliative dermatitis Lymph node & splenic enlargement Haematologic abnormalities: IMHA and/or IMTP – both together is called Evan’s syndrome Lymphopenia with increased CD4:CD8 ratio (SLE <6:1, normal <2:1) Antinuclear antibody (ANA) titre commercially available in dogs

Answer 921

Pemphigus are a group of autoimmune skin diseases Pathophysiology: Immune reaction agains anchoring collagens desmosomes, hemidesmosomes, etc Gross pathology: pustules, vesicles, bullae, erosions, ulcers Histopathology: Acanthosis = epidermal thickening (not specific) Acantholysis = loss of adhesion between epithelial cells (relatively specific) Characterised into different types by location of epidermal damage P. foliaceous = superficial (stratum granularis) P. vulgaris = deeper (stratum basal) Subepidermal forms include: mucous membrane pemphigus, bullous pemphigoid, epidermolysis bullosa

Answer 922

Single gene disorders – autosomal dominant Only one mutated allele is required One parent heterozygous will result in 50% affected offspring Signalment- Persian cats and Bull Terrier dogs Pathogenesis- Polycystin-1 and/or 2 mutated Modify cilia function, cell proliferation and migration-Tubular cell proliferation and fluid secretion Clinical signs- Assoc. with renal failure PUPD Clin path- Low USG Azotaemia Gross pathology- Bilaterally irregular enlarged to shrunken kidneys depending on chronicity Large cysts interspersed by firm pale tan to cream/white (fibrotic) areas In cats cysts are also seen in the liver and pancreas

Answer 923

Only one mutated allele is required One parent heterozygous will result in 50% affected offspring Polycystic kidney disease

Answer 924

Single gene disorders – autosomal recessive Two mutated alleles are required Both parents heterozygous will result in 25% affected offspring Signalment- Young animals, any species Pathogenesis- Result from the lack of any protein that is necessary for the normal functioning of lysosomal degradation pathways. Clinical signs- Vary depending on which part of the CNS affected. Progressive. Ataxia, dysmetria, head and limb tremors Gross- Typically none Potentially increased cerebellar weight if primarily affects cerebellum Histopathology See image Clin path- May see accumulated material in macrophages in blood or CSF Diagnosis- Urinalysis for GAGs Biopsy/PM tissue material – ultrastructure and/or enzyme assay Dried blood spots – enzyme assay

Answer 925

Two mutated alleles are required Both parents heterozygous will result in 25% affected offspring Lysosomal storage diseases

Answer 926

Single gene disorders – X-linked Mutated gene on the X-chromosome- Usually recessive Males worse affected Signalment- Middle aged dogs Goldies Pathogenesis- Dystrophin gene Lack of this gene increases the susceptibility of the muscle fibres to repeated bouts of necrosis, regeneration, and fibrosis Clinical signs and gross pathology- Progressive muscle atrophy Resultant weakness in diaphragm impairs respiration and may result in hiatal hernia Histopath-

Answer 927

Mutated gene on the X-chromosome Usually recessive Males worse affected Duchenne's muscular dystrophy

Answer 928

Rare Chromosomal disorders Turner-like syndrome Horses, pigs XO Clinical appearance- Can go unnoticed until breeding failure Small body size, poor conformation, angular deformities Small and inactive ovaries with an underdeveloped reproductive tract Diagnosis- Karyotyping

Answer 929

Rare X-chromosome monosomy Turner-like syndrome Horses, pigs XO

Answer 930

Poorly characterised Humans Diabetes type 1 Systemic lupus erythematosus The aetiology of the autoimmune disease systemic lupus erythematosus (SLE) is considered to be a combination of multiple genetic and environmental factors whose amalgamation breaches the threshold of immune tolerance.

Answer 931

new growth due to irreversible genetic changes rendering them unresponsive to ordinary cellular controls Other terms: Mass- Enlargement of tissue Neoplastic or otherwise (granuloma) Tumour- Swelling/growth Describes clinical appearance Cancer- Crab Describes infiltrative behaviour Always denotes malignant neoplasms Oncology = study of neoplasia

Answer 932

Initiation: first step of carcinogenesis: introduction of an irreversible genetic change into normal cells by action of mutagenic initiating agent e.g. chemical or physical carcinogens that damage DNA. Mutation induction also requires mispairing of the DNA lesion to produce altered complementary DNA strand thus at least a single round of DNA replication is necessary for genetic change to become permanent. Initiated cells are morphologically normal Promotion: second stage; outgrowth of initiated cells in response to selective stimuli (=promoting agents) that drive proliferation. Promoters are not mutagenic but create a proliferative environment with reversible effects. A benign tumour is the end product of the promotion phase Progression: final stage where a benign tumour evolves into an increasingly malignant tumour = malignant transformation (irreversible change that involves genetic and epigenetic changes). Hallmarks of progression = genetic instability and increasing tumour cell heterogeneity Definitions- Mutagens: agents that cause mutations Carcinogens: agents that cause cancer Complete Carcinogens: An agent that is an initiator and promoter, e.g. radiation The latent period is the time before a tumour becomes clinically detectable Smallest clinically detectable mass is usually ~1cm and contains ~10^9 cells (need 30 rounds of cell division)

Answer 933

first step of carcinogenesis: introduction of an irreversible genetic change into normal cells by action of mutagenic initiating agent e.g. chemical or physical carcinogens that damage DNA. Mutation induction also requires mispairing of the DNA lesion to produce altered complementary DNA strand thus at least a single round of DNA replication is necessary for genetic change to become permanent. Initiated cells are morphologically normal

Answer 934

second stage; outgrowth of initiated cells in response to selective stimuli (=promoting agents) that drive proliferation. Promoters are not mutagenic but create a proliferative environment with reversible effects. A benign tumour is the end product of the promotion phase

Answer 935

final stage where a benign tumour evolves into an increasingly malignant tumour = malignant transformation (irreversible change that involves genetic and epigenetic changes). Hallmarks of progression = genetic instability and increasing tumour cell heterogeneity

Answer 936

controls expression nad activation of protiens involved in the cell cycle acts as a tumor suppressor, which means that it regulates cell division by keeping cells from growing and dividing (proliferating) too fast or in an uncontrolled way. activated p53 can send the cell down numerous pathways- sensecence, repair, apoptosis defective p53 may lea to uncontrolled neoplasms in the event cells are exposed to mutinagens and carcinogens Vet example: Aflatoxin B1 produced by Aspergillus sp. causes mutation in TP53 gene causing G:C  T:A at codon 249. Result is arginine to serine substitution in p53 protein. Strong association between hepatocellular carcinoma and Aflatoxin B1

Answer 937

Single gene disorders of somatic cells NOT heritable Tumorigenesis – see cancer lectures Congenital disorders Rare Single gene disorders of germ cells Heritable Autosomal dominant Autosomal recessive X-linked Single-gene disorders of mitochondria Rare Mitochondrial encephalopathies (Huskies) and myopathies (horses)

Answer 938

NOT heritable Tumorigenesis – see cancer lectures Congenital disorders Rare

Answer 939

Heritable Autosomal dominant Autosomal recessive X-linked

Answer 940

Rare Mitochondrial encephalopathies (Huskies) and myopathies (horses)

Answer 941

Morphology- Tumours resemble normal parenchymal cells Well-differentiated adenocarcinomas of the thyroid form normal-appearing follicles Squamous cell carcinomas may contain cells that appear identical to normal squamous epithelial cells Functional- Retain a lot of normal function Benign neoplasms and well-differentiated carcinomas of endocrine glands frequently secrete hormones characteristic of their origin, e.g. thyroid adenoma Well-differentiated squamous cell carcinomas of the epidermis synthesises keratin Sertolli cell tumours overproduce oestrogen- Paraneoplastic syndrome

Answer 942

Morphology- Lose resemblance to normal cells Criteria of malignancy Anisocytosis – variation in cell size Anisokaryosis – variation in nuclear size Pleomorphism – variation in cell shape Karyomegaly – large nuclei, increased N:C ratio Multiple nuclei Mitoses – indicative of rapid growth. Atypical/bizarre mitoses may be present Loss of polarity – disturbed orientation Large central areas of ischaemic necrosis Functionality- Lost function May gain new and unanticipated functions Expression of foetal proteins or other proteins not normally found in corresponding normal adult cells May produce unexpected hormones- parathyroid-like hormone in anal sac gland carcinoma paraneoplastic syndrome

Answer 943

the occurrence or potential to metastasise

Answer 944

Cancer cells break away from their site or organ of origin to invade surrounding tissue and spread to distant body parts. Some cancers rarely metastasise Criteria of malignancy typically correlate with risk of metastasis Lymphomas and leukaemias are often disseminated at diagnosis and are always taken to be malignant hence the interchangeable terms lymphoma and lymphosarcoma Due to our clinical knowledge, we can predict risk in some tumours in some species in some locations Melanoma in dog mouth is always considered malignant Staging can confirm metastasis (see MCT lecture)

Answer 945

Loosening of intercellular junctions Loss of cell to cell adhesion is a key first step Downregulation of e-cadherins Degradation of the basement membrane- Production of proteases/collagenases Adhesion to ECM- Upregulation of n-cadherins Migration/locomotion- Autocrine motility factor Response to scatter factor Intravasion- Tumour associated macrophages Angiogenesis Tumour emboli- Escape from anoikis Extravasion- Chemokines

Answer 946

Most carcinomas and some sarcomas go this way Lymph node involvement largely depends on pre-existing routes of normal lymphatic drainage. e.g. adenocarcinoma of intestine -> mesenteric LN first However, regional LN’s may be bypassed, so-called skip metastasis—because of venous-lymphatic anastomoses or because inﬂammation or radiation has obliterated lymphatic channels. Recent studies suggest that lymphatic spread does not occur in an orderly fashion and that metastasis to regional lymph nodes indicates that systemic spread has likely already occurred.

Answer 947

Sarcomas use this more than carcinomas Generally invade veins more than arteries because of thinner walls Tumour cells invading veins, go to vena cava, then pass through heart and lodge in capillary beds particularly of lungs Tumour cells that invade portal vein tend to lodge in liver. Pheochromocytomas has a notable predilection for invading veins - likes to invade adjacent caudal vena cava

Answer 948

Aka ‘seeding’ Tumours that arise on surface of abdominal or thoracic structure. Spread over visceral and parietal surfaces e.g. ovarian and pancreatic adenocarcinomas – multiple tumour masses throughout the abdomen. This condition is termed carcinomatosis. Difficult to treat, generally fatal

Answer 949

Mast cells originate from hematopoietic precursors in bone marrow that undergo differentiation and maturation in tissues under the influence of cytokines Have a specific KIT receptor for the stem cell factor, also known as CD117 Why they become neoplastic is not completely understood Some breeds of dog over-represented, therefore genetic- Labrador Retriever (13% of all mast cell tumour claims) Staffordshire Bull Terrier (12%) French Bulldog (7%) Golden Retriever (7%) Boxer (5%) Mutations in the KIT proto-oncogene 20–30% of canine MCT express a mutated form of KIT Mastinib is a chemotherapeutic that inhibits KIT MCTs, in the dog, are typically solitary masses May be within the dermis (cutaneous) Or subcutaneous In the cat they are more likely to be visceral Most common round cell tumour of the feline spleen MCTs, in the dog, are typically solitary masses Within the dermis (cutaneous)- Or subcutaneous Typically singular on the leg or flank Nodular, soft mass Reddening – histamine Ulceration, pruritus, oedema and swelling of limb – histamine Rarely, systemic anaphylaxis and/or vomiting due to histamine’s action on the stomach = paraneoplastic syndrome diagnosis- Fine needle aspirate (FNA)- Cytology Conscious Cheap Quick Can potentially grade but not yet standardised Biopsy- Histopathology GA/ sedation+local Relatively more expensive Results take longer to come back Grading more accurate? Incisional versus excision biopsy margins Stained typically with haematoxylin and eosin Granules in a well-differentiated neoplasm are easy to see In cats and poorly differentiated can be hard to see the granules Giemsa Toluidine blue in cats- iological behaviour varies Most are solitary and benign Cutaneous or visceral? Grading scheme Histological types Prognostic factors not well defined

Answer 950

Histologic grading has been the primary tool for veterinary pathologists to assess the potential biological behaviour of canine MCTs, and it is commonly used for prognostication and therapeutic determination. In 1984, Patnaik et al., came up with a three-tier grading system that became widly adopted Grade 1 - low Grade 2 - intermediate Grade 3 - high There has generally been a shift two-tier grading schemes across medicine and veterinary medicine for various cancers In 2010 the two-tier canine cutaneous MCT grading system by Kiupel, et al., was published High Low According to the Kiupel system (KS), the diagnosis of a high-grade (HG) MCT is characterized by any of the following criteria: At least 7 mitotic figures in 10 high-power fields (hpf) At least 3 multinucleated (3 or more nuclei) cells in 10 hpf At least 3 bizarre nuclei in 10 hpf Karyomegaly (nuclear diameters of at least 10% of neoplastic cells vary by at least two-fold). impoetat for predicting prognosis- Low grade MCTs are composed of relatively monomorphic populations of neoplastic mast cells that have a low nuclear to cytoplasmic ratio, minimal anisokaryosis, single nuclei, often with only one to two nucleoli, and a low mitotic index (A). MCTs are classified as high grade if they meet any of the following criteria: seven or more mitotic figures in 10 high power fields (HPF) (B), three or more cells with three or more nuclei in 10 HPF (C), three or more bizarre nuclei in 10 HPF (D), or karyomegaly and anisokaryosis as defined by nuclear diameters that vary by at least two times in at least 10% of neoplastic cells (E). Density of intracytoplasmic granules, number of eosinophils and amount of supporting stroma are variable between tumors and are not features evaluated for grading. Dogs with low grade MCTs have a significantly longer survival time in comparison to those with high grade MCTs

Answer 951

Mutations in exon 11 of c-kit is an important prognostic indicator in canine mast cell tumours (MCTs). (A) Dogs with MCTs that have mutations in exon 11 of c-kit have significantly shorter survival times. Differences in patterns of expression of the KIT protein have also been associated with prognosis Three distinct immunohistochemical expression patterns of KIT have been described in canine cutaneous MCTs: (B) peri-membrane labelling =pattern 1 (C) focal perinuclear or stippled cytoplasmic with decreased membrane labelling = pattern 2 (D) diffuse cytoplasmic labelling = pattern 3 MCTs with KIT patterns 2 and 3, which represent aberrant localization of KIT protein, have been associated with decreased survival time and an increased incidence of local recurrence

Answer 952

As apposed to grading, which is performed by the pathologist, staging is performed by the clinician with the assistance of a pathologist. Staging is the assessment of whether a tumour has metastasised. T-N-M classification scheme T refers to the local tumour N for regional lymph nodes M for distant metastasis For the majority of tumours, a local draining lymph node is typically the first place it will spread to = sentinel Contrast agent can be used Imaging and/or FNA for distant metastasis Liver and spleen The sensitivity of ultrasound for detecting mast cell infiltration was 43% for the spleen and 0% for the liver. Dogs with positive cytologic evidence of mast cell infiltration to spleen, liver, or both had significantly shorter survival (100 vs. 291 days) than dogs without evidence of mast cell infiltration (P<0.0001). Routine splenic aspiration should be performed regardless of ultrasonographic appearance in dogs with a clinically aggressive mast cell tumour.

Answer 953

are clinical signs or disorders caused by a neoplasm indirectly and distant from the primary mass or its metastases. Cachexia Endocrine tumours- endocrine disease Reproductive tumours- repro disease an hormone production Thymomas- myasthenia gravis, polymyositis, various dermatoses Hypercalcaemia Myeloma Amyloidosis

Answer 954

In cancer cachexia both muscle and fat are lost Starvation is primarily fat at first Pathogenesis- Metabolic catabolism of the neoplasm AND Production of TNF-a (cachectin), IL-1, IL-6 and prostaglandins- Anorexia Lipolysis Insulin resistance

Answer 955

See endocrine week for pituitary adenomas, adrenal-dependent Cushing’s and hyperthyroidism See pancreas dry lab for insulinoma Neoplasm of islet beta cells There are other cells within the islets G-cells -> gastrin

Answer 956

Sertoli cell tumours Oestrogen secretion occurs in 20-30% of Sertoli cell tumours Hyperoestrogenism syndrome Feminization Gynecomastia Bone marrow suppression- Pancytopenia Squamous metaplasia of the prostate gland Alopecia Granulosa cell tumour- GCTs in the horse are associated with 3 behavioural patterns: anoestrous; inhibin-producing nymphomania; continuous or intermittent oestrus; oestrogen-producing male behaviour; androgen-producing Testosterone levels are elevated in most cases, but male behaviour is only observed when serum testosterone levels are very high

Answer 957

Several immune-mediated conditions in humans, dogs, and cats have been associated with thymomas, including myasthenia gravis polymyositis various dermatoses Exfoliative dermatitis is reported in cats and goats with thymomas Due to failure of the thymus to remove self-reactive lymphocytes

Answer 958

Many neoplasms can result in hypercalcemia PUPD is most consistent clinical sign Bradycardia, lethargy, weakness A functional adenoma of the parathyroid gland will over-produce parathyroid hormone (PTH) Most common example of ectopic hormone production is anal sac gland carcinoma Production of parathyroid-like hormone Like normal PTH, acts to increase calcium in the blood Others include- Multiple myeloma Squamous cell carcinoma in the horse Metastatic bone tumours Lymphoma

Answer 959

Neoplasm of plasma cells Differentiated B-cell that produces immunoglobulins (antibodies) Three types of plasma cell tumours: Extramedullary plasmacytomas- Solitary or rarely multiple benign tumours arising in soft tissues such as skin and oral cavity Solitary bone plasmacytomas Multiple myeloma: Involves bone marrow of multiple joints Results in increased immunoglobulins in the blood- monoclonal gammopathy as all the same as all from one neoplastic plasma cell and its neoplastic daughters Part of the light chain of the immunoglobulins is seen as Bence-Jones proteins in the urine Radiography will show osteolysis multifocally Multiple potential paraneoplastic syndromes- Hypercalcemia, due to damage to bone Pancytopenia, due to effacement of bone marrow Haemorrhage, caused by pancytopenia and secondary platelet dysfunction due to the binding of the paraprotein to platelets Hyperviscosity syndrome , due to circulating globulins Renal disease, due to nephrocalcinosis secondary to chronic hypercalcemia, hypoxic damage from hyperviscosity, renal toxicity of light chains and neoplastic cell infiltration into the kidney and/or renal amyloidosis.

Answer 960

Amyloid is a pathogenic proteinaceous substance composed of polypeptides arranged in beta-pleated sheets Amyloidosis is considered a protein-misfolding disorder in which the proteins biologic function is lost Types of amyloid: AL, amyloid light chain; derived from plasma cells; contains immunoglobulin light chains AA, amyloid-associated; an acute phase protein produced in excess, as a result of chronic antigenic stimulation such as occurs in persistent infections, inflammation, or neoplasia Aβ Amyloidosis in the cerebral cortex of aged dogs with canine cognitive disorder or human beings with Alzheimer’s disease Islet Amyloid Polypeptide: amyloid secreting β cells of the pancreatic islets, released with insulin Pathogenesis: Genetic- Kidneys of Abyssinian cats and Shar-Pei dogs Liver of Siamese cats Chronic inflammation Plasma cell tumours Unknown- Nasal amyloidosis in the horse

Answer 961

85% of epidermis Ectoderm function- Skin barrier. Immune response – phagocytes & cytokine production.

Answer 962

(tissue-resident macrophages) origin- Haematopoietic progenitor cells function- Immune response

Answer 963

origin- Neural crests fuinctionMelanic pigment production, UV protection

Answer 964

origin- Epidermal stem cells function- Mechanoreceptos

Answer 965

Infection that develops up to 30 days after surgical procedure OR Up to ONE YEAR if surgical implants placed skin doesnt form bacteril seal until 24-48 hours after surgery can be insisional or organ/ space infections

Answer 966

Exogenous- e.g on skin Endogenous- in the animal Nosocomial - from the vet clinic

Answer 967

Elective, non-traumatic procedure No break in aseptic technique Infection rates (small animal): 2.5-6% Do we need to give antibiotics?

Answer 968

Minor break in aseptic technique Entry into GIT, UG or respiratory tract Infection rates: 2.5-9.5% Give antibiotics ?

Answer 969

Traumatic wound more than 6 hours old Break in aseptic technique Infection rates: 5.5-28% Give antibiotics?

Answer 970

Traumatic wound over 12hrs old Infection rate: 18-25% Give antibiotics?

Answer 971

Structured community of bacterial cells enclosed in a self produced polymeric matrix and adherent to an inert or living surface Quorum sensing Matrix is protective Biofilms grow through a combination of cell division and recruitment Once developed, biofilm allows bacteria inside to become more resistant to antibiotics

Answer 972

Consider flora of surgical site Skin: Dog: Staphs and Streps Cat: Pasteurella multocida Respiratory Tract: Staphs and Streps Not usually a source of infection

Answer 973

Oral cavity: large numbers of aerobic and anaerobic bacteria Upper GIT Smaller numbers aerobes and anaerobes Gram negatives Small intestine (upper SI) = more and more anaerobes Lower GIT (lower SI and LI) larger numbers of bacteria Colon: Far more anaerobes than aerobes

Answer 974

Sterile – under normal conditions Staphs and Streps Coliforms Usually ascending

Answer 975

Dental Procedures Geriatric Patients GIT procedures- can make stool lass solid so this should be considered when rupture is ruisk

Answer 976

MRSA Methicillin-resistant staph aureus Human health risk? Vet ‘antibiogram’ different Spread by direct contact Spread limited by basic hygiene and common sense Any chronic non-healing wound: Think MRSA Swab for C+S Cover wound and barrier nurse or isolate patient Basic hygiene – wash hands after touching any animal stop antibiotics as soon as granulation tissue present Risk factors Antibiotic overuse Antibiotic misuse Patient disease status Number of procedures Hospitalisation

Answer 977

The swim bladder is a hollow organ filled with a gas Main functions buoyancy oxygen storage respiratory functions communication (hearing and sound production) In Cyprinidae (carp which includes goldfish) two chambers, anterior and posterior, linked by a narrow isthmus (ductus communicans) connected to the oesophagus by a pneumatic duct *Connected to the oesophagus by a duct in salmonids *Facilitates buoyancy adjustment by swallowing/expelling air via mouth

Answer 978

Ich/white spot (Ichthyophthirius multifiliis) Gas bubble disease Bacterial kidney disease of salmonids (Renibacterium salmoninarum Infectious salmon anaemia Sea lice Koi herpes virus Fish tuberculosis (Mycobacterium marinarum) - zoonotic

Answer 979

lung or gill heart liver spleen kidnwy stomach small and large intetine brain tounge skeletal muscle pancreas gallblader lymph heart bine eye larynx peripheral nerve cloaca

Answer 980

Because amphibian skin has such unique structural properties and physiologic functions, skin diseases are among the more common causes of death. Poison glands Skin diseases of note Batrachochytrium dendrobatidis Chytridiomycosis Red leg Aeromonas hydrophila and others Capillaria xenopodis Mycobacterium marinarum zoonotic

Answer 981

Risk Carriers of salmonella Venomous snakes can still bite! Oral mucosa with tongue and proximal oesophagus a standard section Diseases of note Boid inclusion body disease Arenavirus Ranavirus Ophidiomycosis

Answer 982

external layer of tfish eye

Answer 983

4 layers of gills on each side made of two rows of fillaments on each arch each have many secondary lamilla giving big surface area that may exede that of skin can be damged easily by pathogens or high C02 responsible for gas exchange, acid base exchange, exchange of nitogenous waste, osmoregulation (ion exchange), immune role water ust flow in contracurrent

Answer 984

Pyramid shaped. Located between liver and gills Circulates blood throughout the body

Answer 985

Located in the midline running the length of the abdomen beneath the spine, obscured by swim bladde osmoregulation, excretion of wastes (posterior portion) manufacture of RBC & immune function (anterior portion ). Smooth uniform surface-wine/brown/black in colour

Answer 986

Largest organ - anterior abdomen around stomach Assists in digestion, fat storage, processing toxins (nitrogen waste excretion)

Answer 987

Dark red, located caudally in abdomen Blood cell formation, immune response, blood filtration

Answer 988

Distributed throughout fat around pyloric caecae Secretes digestive enzymes & hormones.

Answer 989

Located in dorsal abdomen below the swim bladder. In pair connected to the vent (anal/urinary pore), but in salmonids oviduct not fully connected, eggs are released in the peritoneal cavity. in salmonids eggs released into peritoneal caity rather than directly to vent

Answer 990

W-shaped myotome muscles are layered not stiated have red muscle in lateral line and base of finsfor swiming white muscle in body

Answer 991

lso called lateralis system, a system of tactile sense organs, unique to aquatic vertebrates from cyclostome fishes (lampreys and hagfish) to amphibians, that serves to detect movements and pressure changes in the surrounding water. It is made up of a series of mechanoreceptors called neuromasts (lateral line organs) arranged in an interconnected network along the head and body. This network is typically arranged in rows; however, neuromasts may also be organized singly. At its simplest, rows of neuromasts appear on the surface of the skin; however, for most fishes, they lie embedded in the floor of mucus-filled structures called lateral line canals. These canals are placed just underneath the skin, and only the receptor portion of each neuromast extends into the canal. In amphibians the lateral line system occurs only in larval forms and in adult forms that are completely aquatic.

Answer 992

25 – 50% total energy output used for osmoregulationInvolves kidney, gut & gillsFluid & salt balance

Answer 993

Epizootic haematopoietic necrosis- (EHN)Declared free Gyrodactylus salaris (GS)-Declared free Infectious haematopoietic necrosis (IHN)- Declared free Infectious salmon anaemia (ISA)- Declared free Koi herpesvirus disease (KHV)- Undetermined Spring viraemia of carp (SVC) -Declared free Viral haemorrhagic septicaemia (VHS)-Declared free Bacterial kidney disease (BKD)-Not recognised as free. Disease in control nationally.

Answer 994

*Flashing*Rapid opercular movement*Flared gills*Thickening of gill epithelium on microscopic examination*Darkening in fry*Grey patches*Increased mortalities

Answer 995

Skin damage, stress and general weakness *Osmoregulatory failure *Irritation – pain? *Decreased appetite *↑ susceptibility to other diseases *↑ susceptibility to damage/stress during handling

Answer 996

caused by the protozoan Neoparamoebaperurans *Wrasse, Lumpfish and Salmon particularly susceptible *Clinical disease most common between 12-20°C *Can survive on gills of dead fish *Can cause high mortalities (hatcheries and pens) *Proliferation of lamellar epithelium and increased mucus production

Answer 997

*Flagellated protozoa *Parasite may be free swimming or attached to fish cells. *Free swimming shows erratic rapid movement easily seen under low power (x10), *Observation of flagellae under higher power confirms identification. *Attached stages can be seen round edges of secondary lamellae. *Treatment: Formalin baths

Answer 998

*Ciliated parasite *Large parasite (easily seen under low power), free swimming, with slow, undulating motion, appears to graze over edge of gills. *Increases mucus, hypoxia *Treatment: Formalin baths

Answer 999

*Ciliated parasite *Large (easily seen under low power), free swimming, with circular motion, using numerous cilia round edge (look like flying saucers). *Treatment: Formalin bath

Answer 1000

*Icthyophthirius multifilis *Ciliated *Several life stages occur but identification is usually on large mature stage embedded in fish skin. Horse shoe shaped nucleus is easily identifiable feature. *Skin & gill irritation, respiratory distress. *Micro skin lesions*Stress *Prevention/management: Good tank hygiene, disinfection of equipment. *Treatment: Formalin bath

Answer 1001

Capriniana sp. (Tricophyra) *Scyphidia *Fixed in place *Feed on organic matter in water

Answer 1002

Tetracapsuloides bryosalmonaePrimarily occurs during summer Gross lesions: Darkened body color, exophthalmos, pale gills, abdominal swelling, ascites, splenomegaly, and enlargement of kidney Management: Clean environment, reduce stress, reduce temperature

Answer 1003

*Acute septicaemia: persistent increased mortalities *Chronic: furuncles, skin lesions *Outbreaks generally >16°C *Horizontal transmission: water column, direct fish-to-fish, vectors CLINICAL SIGNS: -Sudden death (acute infections) -Lethargic swimming, surface-swimming (fish with exophthalmia) -Loss of appetite, respiratory distress, fish jumping from water -Haemorrhages in internal organs, enlarged spleen and focal liver necrosis, congested GIT PREVENTION & CONTROL*Vaccination*Antibiotherapy*Biosecurity

Answer 1004

*Acute septicaemia *High survival in environment (months) *Horizontal transmission: fish-to-fish *Once in the system, difficult to clear *Carrier status possible CLINICAL SIGNS:*Unspecific *Increased mortalities *Fish swimming near surface or tank-edges *Dark colour *Poor feeding response CONTROL: *Vaccination, Antibiotherapy, biosecurity

Answer 1005

Salmon, Wrasse and lumpfish (SW) T. maritimum, T. dicentrarchi, T. finnmarkense External lesions, gill/fin rot, systemic infection Predisposing factors: Water temperature, poor water quality, skin damage, jellyfish?

Answer 1006

Notifiable Clinical signs:*Dark coloration, exophthalmos, pale gills, abdominal distension, or hemorrhages at the vent or base of the fins. *Kidney- nodular masses Control: Appropriate antibiotic / appropriate biosecurity. If outbreak is observed, follow eradication plan.

Answer 1007

*Classical vibriosis *23 serotypes (only 01, 02a/ß and 03 pathogenic) Serotype 01 *Also infects salmonids *Serotype most regularly isolated from cleaner fish Serotype 02a/ß *Often isolated in other marine species Signs:*High mortalities, lethargy, loss of appetite*Superficial congestion and haemorrhage *Systemic infections: similar to furunculosis May be present in the gut of healthy fish and be stress activated

Answer 1008

Observed during colder months Affects osmoregulation Might heal, but leaves scarring tissue and melanisation Wild wrasse (UK), lumpfish in Ireland, Iceland Research indicates differences between salmon and lumpfish isolates in Iceland

Answer 1009

Significant pathogen of Atlantic salmon, has also been observed in Rainbow trout & Lumpfish Facultative intracellular bacteria Clinical signs:Lethargy, haemorrhagic skin lesions, ascites, discolouration of heart (fibrinous epicarditis) and liver, pale gills, swollen kidney, granulomas in liver or spleen.Petechial haemorrhaging of GIT and swim bladde

Answer 1010

Pasteurella skyensis affects Salmon SW *Two serotypes, O2 in Scotland *Lethargy, skin darkening *Anaemia, petechia in internal organs and muscle Pasteurella sp.in Lumpfish *Head ulcers, white spots on skin, bleeding gills, tail rot *Granulomas, white nodules on organs, swollen spleen, ascite

Answer 1011

Affects Lumpfish External signs *Redness in lower jaw, cheeks, around ventral part of body and pectoral fins, darkening of last third of body flanks. Internal signs *Enlarged kidney and liver, ascites

Answer 1012

fungus in fish Economically significant pathogen to FW aquaculture around the world Characterised by white/grey patches of filamentous hyphae Saprolegnia diclina- infects eggs Saprolegnia parasitica- infects fish Represents major source of losses in FW salmonid aquaculture MANAGING THE DISEASE Bath treatments – early treatmentGood tank hygiene and water quality Minimise stress Remove mortalities

Answer 1013

fungus in fish Affects lumpfish: Black lesions observed in all tissues (heart, gills, caecae, liver, kidney, spleen, muscle, skin.)

Answer 1014

IPN is a disease of stressed salmonids! *Clinical disease generally occurs when fish are most vulnerableor subjected to heaviest stresslevels. Freshwater and marine stages (most vulnerable after hatching). *In fry IPN generally occurs within 3-4 weeks of first feeding. Onset of disease can be explosive with up to 90% losses. *Mortality level is often related to stocking density and environmental conditions, survivors become carriers (faeces, gonad fluids, mucus, urine). External signs- Loss of appetite- Sluggishness - Spiral swimming- Protruding vent- Trailing cast- Popeye- Swollen belly- Change in pigmentation Internal signs- Pale liver (consistent finding in fry, liver looks like condensed milk)- Ascites- Visceral fat petechiae- Empty gut with whitish or yellow exudate

Answer 1015

*Detected in Norway, Scotland, Ireland, Faroes*Suspect Pox Virus damages epithelium and paves the way for other pathogens *Compromises mucosal defense of the gills. *Clinical signs -described mainly for salmon fry: loss of appetite, lethargy and crowding in the bottom of the tank (respiratory distress). *On gross examination the gills appear pale and the filaments swollen.

Answer 1016

Virus infection targets: *(Systemic – general weakness/lethargy) *Pancreas = impaired food digestion/absorption *Heart = increased susceptibility to stress/handling *Skeletal muscle = impaired swimming Clinical appearance (signs observed, mortality level etc) can be quite variable. Typical signs include: -Lethargy, altered appetite, fish “hanging about”, fish spiralling to the bottom of the pen, thin snake-like fish, yellow faecal casts, sudden death at handling, poor FCR PREVENTION= Vaccination / fallowing / SD / good condition fish MONITORING= serology/PCR MANAGING THE DISEASE Disease stages:Viraemia (early stages of the infection) careful management! Avoid stressAntibodies (late stages – from 3 weeks post-infection)Samples to assess level of damage (CPK, histology)Remove morts

Answer 1017

Virus infection targets: Heart = increased susceptibility to stress/handling.Liver (probably secondary changes to heart damage. *Signs: Ascites/oedema due to heart failure.Fibrin around heart and/or liver.Enlarged heart. *Usually affects large fish close to harvest – only noticed when fish die at harvest crowd. *Corkwing and ballan wrasse on 2 sites in Ireland *Wrasse have to be considered potential vectors *In 2017, increased incidence in smaller fish, with very high mortality in some cases.

Answer 1018

This virus is found in almost all farmed salmon, however not all salmon will develop this disease!-> THIS IS AN IMPORTANT REMINDER THAT THE PRESENCE OF A PATHOGEN DOES NOT ALWAYS MEAN DISEASE WILL OCCUR!!! Virus infection targets: *Heart = increased susceptibility to stress/handling *Skeletal muscle = impaired swimming *Red blood cells (?associated with blood cell disorders?) *(Systemic – general weakness/lethargy?)

Answer 1019

Contagious viral disease *Causes severe haemorrhaging & anaemia *Can lead to significant mortalities *Notifiable disease

Answer 1020

Contagious viral diseases, mainly FW but can be observed in SW Notifiable diseases, outbreaks require compulsory slaughter UK approved zone, disease freeBoth are caused by Novirhabdovirus Vertical & horizontal transmission, affects all ages, several types of salmonids and other species too. IHN Signs are: Lethargy, anaemia (pale gills and internal organs), exophthalmia, haemorrhagic fins, ascites. VHS signs are: Exophthalmia, ascites, dark skin, haemorrhages in internal organs and muscle, pale gills. Control: Biosecurity, use of disease free ova. Screening of fish prior reception

Answer 1021

Repeatedly detected in lumpfish in Norway and the UK High mortality has been attributed to the infection Histology characterized by liver pathology Research ongoing

Answer 1022

CLuTV, anecdotal experience: Detected in alevins and juveniles, mainly during presence of intestinal Vibriosis, associated to “diarrhoea” (co-infection?)*Not detected any more from young adults CLuCV, anecdotal experience: *Detected in adults, no clear mortalities associated to it yet. Both viruses still under research

Answer 1023

Water quality- Environmental gill disease NephrocalcinosisGas bubble disease Supersaturation Physical/environmental- Algae/JellyfishPredation UV, electrocution Behavioural- Tail biting (stress, light, lower stocking densities?) Mitigated by environmental enrichment? Air gulping Management related- High susceptible to stress, handling Welfare important Cataracts - Likely nutrition related infectious Linked to fast growth/high temperatures? Light wavelength- green light 520nm? Nutritional - Deficiencies Fat rancidity Mycotoxins Deformities- Sucker deformities common problem in lumpfish Skeletal deformities underdiagnosed? Egg incubation temperatures, nutrition, ... Haemorrhagic smolt syndrom Skin lesions: *Open doors to other infections *General weakness *Decreased appetite *Irritation – pain? *Osmoregulatory failure *PREVENTION = Adequate/careful handling *MONITORING= check fish condition (morts, divers, sub-sampling) *MANAGING THE DISEASE *Careful handling *Antibiotics needed? *FW/disinfectant bath

Answer 1024

Physical/environmental Algae/Jellyfish: Plankton Reduce O2 content in water Physical damage Toxic damage Supersaturation Vectors for bacteria Sublethal exposure to harmful plankton is stressful & increases disease susceptibility Harmful plankton can affect wild fish, however farmed fish at significantly greater risk because they are unable to escape in the face of a bloom.

Answer 1025

Clinical findings:* Red marks on flanks and beneath fish* Lesions only skin deep* No other gross effects* No mortalities* If fish left alone, lesions resolve in a few weeks Antibiotic successful Cause unknown (probably bacterial) Can be prevented by use of high levels of vitamin C and glucans Histopathology:* Dermatitis involving the epidermis* Dermis and sub-dermal tissues usually unaffected* Epithelial hyperplasia

Answer 1026

Severe dermatitis affecting Rainbow trout: *Excess mucus on flanks of fish – no parasites*Oedema of skin*White or grey skin patches +/- petechial haemorrhages → raised, reddened “blister” lesions and scale loss. Associated with a very low mortality, but potentially significant economic losses for affected farms due to downgrades, the need for culling and increased production costs. Usually affects 1kg+ triploid rainbow trout, however, could affect smaller (400g) too. Similarities between PSD, RMS and SD, but they can be differentiated based on their epidemiological and clinical characteristics. Not yet seen in brown trout or other salmonids Seen year-round, temperatures between 5.4 and 16.9 °C but prevalence and severity greatest during late summer and autumn, declining over winter

Answer 1027

Bovine tuberculosis (bTB) Mycobacterium bovis Gram positive, acid-fast Slow growing, long incubation period Shed through urine, faeces, sputum and discharge from bite-wounds Badgers are highly susceptible to M. bovis infection Often latent, subclinical infections (no visible lesions) Stressors: concurrent disease, pregnancy, old age Primarily respiratory disease  progression to systemic dissemination testing- Culture pooled tissue (Lowenstein-Jensen, Stonebrink or Middlebook 7H11 culture mediums) Gold standard (6-22 weeks) Post-mortem examination Ziehl-Neelsen stain Cytology or histology sections PCR – APHA (PM tissue samples) gross leasions- Experimental infection (left) Respiratory inoculation Mimics severe disease in naturally-infected badgers (right) Multifocal to coalescing 1-2 mm diameter discrete pale yellow to white tubercles, to extensive miliary lesions Lobar caseation and consolidation Lymphadenomegaly Oedema Multifocal to coalescing pale yellow to white Systemic dissemination ->renal disease Radial granulomatous nephritis Histologic features differ slightly from bTB in other species No encapsulation, abscessation, or layered organised granulomas with multinucleated giant cells Epithelioid cells (E) are surrounded by fibrosis (F) with lymphocytes, plasma cells, macrophages and neutrophils +/- central necrosis (N) Granulomas within a lymph node Similar histologic pattern Centre of epithelioid cells surrounded by fibrosis and inflammation Badger are implicated in the transmission to cattle Small ruminants are susceptible (goats and sheep) Zoonotic risk - human tuberculosis

Answer 1028

Implicated in the transmission of lungworm to dogs Often subclinical / asymptomatic Canine lungworm - Angiostrongyliasis Angiostrongylus vasorum AKA French heartworm L3 (ingested infectious stage) Adults found in lungs & heart Right ventricle / pulmonary artery Eggs in lung capillaries L1 coughed up testing- A. vasorum SNAP test - ELISA Blood sample Good sensitivity and specificity Rapid and reliable Ante-mortem Faecal smear Distinctive kinked tail of L3 larvae Baermann faecal flotation Detection of L3 larvae Eggs aren’t shed so we can’t use a worm egg count Time consuming Low sensitivity due to intermittent shedding Pool faeces over multiple days gross leasions- Adults in right ventricle and pulmonary artery Pulmonary hypertension Right sided heart failure (cor pulmonale) Caudodorsal firm, bulging nodules Consolidation histology- Presence of eggs and larvae within airways Granulomatous inflammation (macrophages and multinucleated giant cells) Adults in vessels Loss of alveolar structure Fibrosis Source of infection for dogs Greater chance of transmission in urban environments Slugs / snails are required for the life cycle - wet environments Can induce haemostatic dysfunction in infected dogs Mucosal bleeding Scleral bleeding

Answer 1029

Squirrel pox virus - poxvirus Poxviruses are resistant and survive outside the host Occurs in England in areas co-inhabited with grey squirrels Asymptomatic in grey squirrels Transmission via body fluids and shared parasites Rapid loss of body condition and subsequent death ELISA (antibodies) Post mortem examination Histopathology PCR Electron microscopy Raised crusting and erythematous dermatitis Oral, periocular, vulvar folds, nail bed Poor body condition Epidermal ulceration Ballooning degeneration of the intact epidermis Mixed inflammatory dermatitis Intracytoplasmic eosinophilic viral inclusion bodies within keratinocytes

Answer 1030

RHDV2 - Type 2 subtype is now most common Calicivirus - Lagovirus Shed in secretions - direct contact and indirect through fomites / ectoparasites High mortality in domestic and wild rabbits Death 48-72h following infection Peracute: no clinical signs, sudden death Acute: anorexia, ataxia, abnormal behaviour, conjunctival congestion Subacute: similar clinical signs, not as fatal testing- PCR (RHDV1 + RHDV2) Post mortem Histopathology Immunohistochemistry gross lesions- Sudden death Splenomegaly Widespread haemorrhages DIC histology- Multisystemic haemorrhages (DIC) Acute splenic necrosis Portal to diffuse hepatic necrosis Disassociation of hepatic cords Electron microscopy (research)

Answer 1031

Avian influenza virus Predominantly affects poultry and waterfowl Rare spill-over detected in wild mammals UK detection Foxes European Otters Grey seals testing- PCR detection Immunohistochemistry Detection of virus antigen Reddish brown = positive

Answer 1032

AMR and anthelmintic resistance Zoonotic disease detection and control Statutory reporting of notifiable and reportable diseases Food safety – residues and contamination Detection of threats to international trade Reporting adverse reactions to Veterinary Medicines Directorate (VMD) Gathering evidence to inform field studies and targeted surveillance Helping build valuable archive of samples APHA Veterinary Medicines Directorate (VMD) SAVSNET VetCompass Cats Protection Dogs Trust RSPCA SSPCA City of London, Heathrow Animal Reception Centre BSAVA ESCCAP UK & Ireland DEFRA Trade Team Veterinary Medicines Directorate (VMD)

Answer 1033

January 2020: Vet in Liverpool raises concerns of increased cases of acute, severe vomiting in dogs (~40 cases) – approaches SAVSNET SAVSNET: data on main presenting complaints and free-text mining from electronic health records 2014-2020 – significant rise in cases between December 2020 to March 2020. Parallel significant rise in the use of maropitant (anti-vomiting drug) Spatiotemporal mapping showed clustering in NW and SW England and Edinburgh February – March 2020: Rapid case-control questionnaire survey of 1200 owner-reported cases. February 2020: Looked back at diagnostic data Jan 2017 – Feb 2020: PCR of enteric diseases including Giardia, Clostridia, Parvovirus, Canine Enteric Coronavirus (CeCoV) February – March 2020: Rapid case-control questionnaire survey of 1200 owner-reported cases in 4.5 weeks. Male dogs and dogs in contact with other vomiting dogs significant No obvious association with SARS-CoV-2 February 2020: Looked back at diagnostic data Jan 2017 – Feb 2020: PCR of enteric diseases including Giardia, Clostridia, Parvovirus, Canine Enteric Coronavirus (CeCoV)

Answer 1034

Owner wants confirmation that it was not their fault that their pet died *Owner wants to know why their pet died *Owner wants to know if it is somebody else's fault e.g. the vet's that their pet died *Owner wants to know if the neighbourpoisoned their pet. *Vet wantsto know what went wrong/ what was missed/ what could they do different *Welfare investigations e.g. RSPCA or Police *Grouped kennel/ breeding setting

Answer 1035

Owner wants to know what they can do to prevent cohort animals being sick/ dying *Owner wants to know why their individual animal died *Owner wants to know why their treatment attempts didn't work *Owner wants confirmation of cause of death for insurance purposes *Welfare investigations e.g. RSPCA, Police, Trading Standards

Answer 1036

carry out a PM/ further investigationsWhat to do instead? Call the Defra Rural Services helpline (APHA)

Answer 1037

Group 1 Unlikely to cause human disease. * Group 2 Can cause human disease and may be a hazard to employees; it is unlikely to spread to the community and there is usually effective prophylaxis or treatment available. * Group 3 Can cause severe human disease and may be a serious hazard to employees; it may spread to the community, but there is usually effective prophylaxis or treatment available. * Group 4 Causes severe human disease and is a serious hazard to employees; it is likely to spread to the community and there is usually no effective prophylaxis or treatment available ACDP cat 4: currently unlikely to encounter in the UK in routine PMEs e.g. Ebola, Hendra Virus. Though beware old-world primates (esp macaques) potential carriers of cat 4 Herpesvirus B! ACDP cat 2: various common pathogens (incl Leptospira spp, Listeria spp, Pasteurella spp etc) that can result in significant disease in individuals and one of the reasons why to wear appropriate PPE when carrying out PMEs. Includes also pathogens like Chlamydia abortus or Toxoplasma gondii – higher risk if pregnant or immunocompromised! ACDP cat 3: main zoonotic concern in the UK especially if pathogen can aerolise. Risk assessment of potential presence needs to be done prior to considering if carrying out any PME

Answer 1038

ACDP3 and notifiable/ reportable zoonotic diseases potentially found in UK: * Bacillus anthracis – consider in all sudden death animals esp cattle (last case in the UK in 2015) and in cases of throat swelling in pigs * Mycobacterium bovis – TB (concerns include alpacas) * (Brucellosis – UK free of Brucella abortus and melitensis but some cases of B canis now in dogs and brucellosis in marine mammals) * BSE – all 'fallen stock cattle' over 48 months of age must have their brainstem tested for BSE * (Highly Pathogenic Avian Influenza – poorly defined zoonotic risk and changing) (some) ACDP3 pathogens present in the UK * Q-fever (Coxiella melitensis) - esp abortions of ruminants esp goats * Chlamydia psittaci – birds esp psittacines and pigeons * Louping Ill (tick-borne disease) - esp sheep and grouse

Answer 1039

Histopathology / (Cytology) Bacteriology/ Microbiology Virology Parasitology Biochemistry / Toxicology

Answer 1040

Where do we collect the sample into? ▪ 10% neutral buffered formalin (CAVE: fumes have carcinogenic potential) What is the “perfect” sample for histopathology? ▪ <1cm thick but wide and long enough to be representative of lesion (fixation speed approx. 1mm per hour) ▪ From the edge of affected to unaffected tissue ▪ Handle carefully, don’t squash, avoid contamination etc Ratio sample size to fixative volume ▪ >10 times the volume of formalin compared to tissue volume

Answer 1041

Requirement of live bacteria for culture Avoid contamination Swab (charcoal medium), taken in a sterile manner (e.g. heat searing of surface), or large section of tissue (into sterile container) Preferred location of sample: edge ↔ centre of lesion ▪ Previous treatment with antibiotics ▪ Abscess/ granuloma Aerobic (routine and/ or selective) ↔ anaerobic Keep sample cool Bacteriology – alternatives for bacteria growing poorly in routine culture media Selective media required Anaerobic culture with adapted sample technique Special staining/ labelling of impression smears (or histopathological sections) PCR Histopathology +/- special stains +/- IHC Toxin detection rather than bacterial detection

Answer 1042

PCR ▪ Piece of affected tissue or swab Viral culture/ isolation ▪ Viruses very fragile, often dead in PM samples ▪ Very expensive Histopathology +/- Inclusion Bodies +/- IHC ((paired) serology

Answer 1043

Helminths * Worm egg count e.g. McMaster's * Total worm count: Washing of contents of abomasum and small intestine with subsequent sieving and microscopic assessment * Visualise grossly esp fluke, tapeworm, Haemonchus spp, lungworm Ectoparasites * Skin scrapings * Histopathology * Visualise grossly e.g. lice Protozoa * PCR e.g. Toxoplasma, Neospora * Histopathology e.g. Histomonas spp * Scrapings/ Worm egg counts/ Flotation/ Smear +/- stain e.g. Coccidia, Giardia, Cryptosporidia spp Blood-borne parasites * PME not diagnostic test of choice * PCR

Answer 1044

post mortem blood? What makes sense testing? * Haematology: useless * Biochemistry: useless; apart from ZST in neonatal animals if only minor haemolysis of sample * Serology: sometimes possible if test not very sensitive to haemolysis +/- only minor haemolysis * Urine * Glucose * Other parameters unreliable – sloughing of mucosa Tissue analysis: liver ↔ kidney ▪ Suspect acute toxicities: predominately testing of kidney tissue as toxin is circulating in blood stream (excretion via kidneys) ▪ Mineral status/ chronic phase of toxicity: test storage organ, e.g. liver for copper, selenium, cobalt Keep tissue frozen (minimum tissue size: > 10g !) – can be processed later Eye fluid analysis (collect asap after death; <48 h): ▪ Vitreous/ aqueous humour esp Mg, Urea, Ca, BHB, nitrate/ nitrite * Use of ocular fluids to aid postmortem diagnosis in cattle and sheep Toxicology for plant poisoning? Clinical history as guidance – look at the field/ environment Look for plant fragments in the gastrointestinal tract * E.g. yew, rhododendron, pieris, acorns No testing available for many “fast acting” plant toxicities Histopathology for some “slower” plant toxicities to provide evidence of toxic effect rather than plant aetiology e.g. ragwort (liver

Answer 1045

Collect the following samples on PM: ▪ Stomach + intestinal contents ▪ Liver ▪ Kidney ▪ PM blood ▪ Urine ▪ Fat ▪ Brain (if suspect organophosphate poisoning) Freeze unless there is evidence of involvement of a specific toxin that can be tested for. If suspicion of poisoning persists after histopathology, discuss possibilities/ options with owner. You will need to provide the testing laboratory with a list of what you want to test for (and find out if available): limiting additional factors include costs, lack of “normal” background reference range

Answer 1046

strong indicator of imaciation rules out sudden death

Answer 1047

InfectiousMetabolic/ feed-relatedToxic Traumatic, accidental, miscellaneous

Answer 1048

Pigs: especially Clostridium perfringens type C –Necrotising enteritis Sheep: especially Clostridium perfringens type D –Pulpy kidney disease Goats: especially Clostridium perfringens type D –Necrotising enteritis Cattle: especially Clostridium chauvoei–Blackleg Other Clostridia sppto consider: Cl. novyi(Black disease), Cl. perfringens type B (lamb dysentery), Cl. tetani, Cl. botulinum, Cl. difficile (Cl. septicum, Cl. sordelli, Cl. haemolyticum, Cl. perfringenstype A)

Answer 1049

Pericardial fibrinous effusionConing of the cerebellum Advanced autolysis kidneys Widespread haemorrhages (e.g. kidney, heart) Glucosuria Confirmation of diagnosis? Toxin ELISA on ileal content (Histopathology brain)

Answer 1050

Usually shortly post-weaning*Intestinal infection with E.colistrains that produce Shiga/ Verotoxins(STEC/ VTEC) with subsequent toxaemia*PM findings: from none to oedema especially subcutaneously (face and eyelids), the greater curvature of the stomach and the mesocolon *Diagnosis?*Isolation of specific serotypes of E.coli and/ or toxin gene PCR in intestinal contents *Histopathology brain

Answer 1051

Worm egg count on large intestinal contents –limitations? *WEC cannot distinguish between trichostrongyle-type eggs (strongyle eggs) e.g. Haemonchus, Teladorsagia, Trichostrongylussppetc *Disease during prepatencyperiod especially NematodirusbattusGrossly visible HaemonchussppTotal worm count –washing abomasum/ C3 and small intestine –sieving contents through a defined sieve size-microscopically count and identify present nematodes

Answer 1052

Hypomagnesaemia (staggers) (Hypocalcaemia)Vit E / SeCCN / PEMRuminal acidosisBloat‘Redgut’ Stomach ulcers Caudal Vena cava syndrome

Answer 1053

Possible clinical presentation? *Sudden death with a large pool of blood around nose/ mouth (DD: anthrax) What does the arrow point to? ▪Thrombus in a pulmonary vessel How did it get there? ▪Thromboembolism e.g.from the caudal vena cavaMost likely pathogenesis? ▪(Subacute/ subclinical) ruminal acidosis → rumenitis → liver abscesses → caudal vena cava abscess/ thrombus → thromboembolism to smaller lung vasculature → vascular erosion and haemorrhage

Answer 1054

Hypomagnesaemia: ocular fluid (vitreous humour) Hypocalcaemia: ocular fluid (aqueous humour) Vit. E/ Se deficiency- *White muscle disease (gross and/ or histo): multifocal muscle necrosis *Mulberry heart disease: pericardial effusion, stripy haemorrhages heart (angiopathy) *Massive hepatic necrosis *Diagnosis: histopathology, liver Se, cohort blood biochemistry CCN / PEM- *Mostly associated with Vit B1 def/ Thiamine *Autofluorescence brain under UV light (some) *Histopathology brain *Differential diagnoses: sulphur-toxicity, lead toxicity, water deprivation/ salt poisoning

Answer 1055

Copper poisoning- *PM findings: anaemia, jaundice (pre-hepatic icterus) *Diagnosis: tissue biochemistry –KIDNEY! Lead poisoning- *Diagnosis: tissue biochemistry –kidney Iatrogenic -*E.g. Nitroxynil BEWARE! Food Safety Incidents

Answer 1056

the evolutionary development and diversification of a species or group of organisms, or of a particular feature of an organism

Answer 1057

the development of an individual organism or anatomical or behavioural feature from the earliest stage to maturity

Answer 1058

raised ridges of brain

Answer 1059

ridges of brain

Answer 1060

6,7,8,9,10,11,12

Answer 1061

a type of cell that provides physical and chemical support to neurons and maintain their environment. Located in the central nervous system and peripheral nervous system, glial cells are sometimes called the "glue" of the nervous system,

Answer 1062

Blood brain barrier integral to protect from infection and toxins Glial cells are effectively the nervous system of the brain Phagocytosis

Answer 1063

long-lived post-mitotic cells Lipofuscin- Age-related and incidental Overproduction/acceleration associated with some diseases (lipofuscinosis)

Answer 1064

Neurones are most susceptible to injury High energy requirement No internal stores of glucose Limited ability to cope with accumulation of intracellular calcium- important factor in repairable damage and non repairable Are terminally differentiated in the adult – no repair Neuronal injury and death looks just like injury in other cells with some key differences: Chromatolysis Shrunken RED IS DEAD However, overhandling fresh brain at post mortem causes this artefact Edges only? Neurones can die via necrosis (oncosis) and apoptosis Glial cells will proliferate and there will be increased infiltrating leukocytes starting at the vessels None of the above are particularly specific for cause Just like in any other part of the body, acute inflammation is associated with vascular changes that can result in oedema In the brain this has dire consequences due to being encased in the skull Flattened gyri Herniation- cerebellum herniates out of skull resulting in coning Vascular occlusion

Answer 1065

Response of axons and myelin to injury- Swollen axon Degeneration and loss of myelin sheath Macrophage infiltration Proximal and distal axon will also degenerate Degeneration of neuronal cell body will also occur Again not pathognomic for cause but frequently seen with anything that causes spinal cord compression -disc disease -cervical myelopathy

Answer 1066

Aged dogs and cats develop deficiencies in learning and memory- In dogs is referred to as canine cognitive dysfunction- May be analogous to Alzheimer's : Senile plaques and cerebrovascular amyloidosis (a blob of pink material assosiated with inflamatory proceses) See DMJ’s lecture Also, a syndrome characterised by severe and acute but typically (partially) transient defect of the central vestibular system (vestibular syndrome) is seen in dogs -Idiopathic

Answer 1067

Myasthenia gravis- Can be congenital or acquired Congenital form- Mutation in one of several genes associated with normal production or function of acetylcholine Acetylcholine stimulates muscle contraction And is main neurotransmitter in parasympathetic system megaoesophagus can occur- apears as regurgitation Acquired form- Due to autoantibodies against the acetylcholine receptor- Thymic mass Tensilon/edrophonium test- Anti-cholinesterase

Answer 1068

The brain is reliant on glucose Diseases the cause hypoglycaemia will result clinically in collapse, coma and/or seizures- Diabetes mellitus Insulinoma Very metabolically active and post-mitotic Heavily reliant on anti-oxidants Thiamine- Deficiency in cattle results in polioencephalomalacia (PEM) also known as cerebrocortical necrosis (CCN) Typically due to sudden shift to concentrates or sulphur contamination of food or water Wandering, circling, cortical blindness, incoordination, head pressing, recumbency, nystagmus, and seizure activity Gross swelling of the brain fluorescence The brain is also reliant on electrolytes Dairy cows may suffer events of hypocalcaemia and hypomagnesemia, commonly known as milk fever and tetany respectively. Milk fever is characterized by hypocalcaemia at parturition as a consequence of a sudden increase in Ca demand and an unavoidable delay in Ca metabolism adaptation. Post mortem collection of aqueous humour Tetany is due to impaired Mg absorption from the rumen that cannot be compensated by absorptive or excretory adaptation, resulting in a net nutritional shortage of Mg and culminating in hypomagnesemia. Lactating grazing cattle on lush pasture Post mortem collection of vitreous humour Copper deficiency Ddx = lead poisoning, water intoxication, hypoxia, In cats deficiency is associated with eating raw fish (thiaminase), poor food formulation (recent outbreak in UK cats) or sulphur contamination in food Classic symmetrical haemorrhages in thalamus

Answer 1069

“Sway-back” (congenital) in lambs or enzootic ataxia (acquired as neonates) in lambs and kids Most common in lambs aged four to twelve weeks old Ascending paresis/paralysis and ataxia Pathogenesis = myelin degeneration May be true copper deficiency, or high sulphur or molybdenum Grossly – the brain is collapsed with bilateral symmetrical cavitation of the white matter Ddx – Bluetongue and Border disease virus

Answer 1070

Endogenous Hepatic encephalopathy- shunts or acquired liver disease, Ammonia Renal encephalopathy Ketosis Exogenous List is practically endless! See toxicology week Both?! Water deprivation/salt toxicosis Seen in animals deprived of water that suddenly are allowed to drink ad lib Pigs are particularly susceptible botulinum protiene cleaves protien that allows for the fusing a acetyle choline lysosomes with axon testnus toxin does the same but acts on inhibitry inter neurons cause=ing uncompramised release of acetyle choline Decreased water intake -> dehydration and increased plasma sodium, which moves passively into CSF -> high sodium inhibits anaerobic glycolysis in the brain -> cerebral energy production decreased -> sodium cannot be actively transported from CSF back to plasma -> increased osmotic gradient -> with regained access to low-ion water, oedema -> increased pressure -> necrosis

Answer 1071

Neurones are post-mitotic therefore tumours of neurones are rare in adults Neuroblastomas, ganglioneuroblastoma and ganglioneuromas are however seen in young animals In the dog the most common location for a peripheral NB is dorsal cranial abdomen (peri-renal) due to remnants of neural crest Olfactory neuroblastomas are rare tumours of the caudal nasal cavity and seen in older animals Therefore, tumours of the CNS and PNS are typically from supporting structures Meninges = meningioma- Most common in cats. good prognosis Glial cells = glioma/glioblastoma- Over-represented in brachys, MOST COMMON BRAIN TUMOUR IN DOGS. poor prognosis Peripheral nerve sheath tumours PNSTs Tumours of Schwann cells (Schwannomas or neurofibromas) Brachial plexus – dogs Skin of the eyelid - cattle

Answer 1072

PNSTs Tumours of Schwann cells (Schwannomas or neurofibromas) Brachial plexus – dogs Skin of the eyelid - cattle

Answer 1073

Do animals have strokes? Stroke in humans refers to an acute blockage of the vessels in the brain resulting in ischaemia to dependent tissue = infarction More common in humans due to vessels already narrowed by atherosclerosis which is rare in animals Infarction of the CNS of animals can otherwise be due to Fat emboli – risk of orthopaedic surgery Fibrocartilaginous emboli – associated with disc disease Anything that causes hypercoagulability could cause an infarction in the brain- In dogs shown to be associated with CKD or hyperadrenocorticism Vascular brain disease in the cat- Feline hypertensive encephalopathy Feline ischaemic encephalopathies- Not in UK – Cuterebra larvae migrate to middle cerebral artery and occlude it resulting in massive infarction

Answer 1074

Naturally affected species- Bovine spongiform encephalopathy – cattle, goats, exotic ungulates, felines (zoonotic!)- notifiable Scrapie – sheep and goats- notifiable Chronic wasting disease –cervids- notifiable Camelid prion disease –dromedary camels (others?) Transmissible mink encephalopathy – mink * Two disease forms in BSE, scrapie and likely CWD Classical form (original) Atypical form (more novel) H-type and L-type BSE

Answer 1075

* Transmissible- From dam to offspring Lateral transmission (scrapie) * Affects more than 1 animal * Wide age range 4-6 y in cattle (21 m-22 y) ≥18-24 m in sheep/ goats * Detectable prions in lymphoid tissue using standard tests Distal ileum Various lymph nodes in sheep Atypical and classical cases have different legal consequences Diagnosis by Western immunoblot or immunohistochemistry

Answer 1076

Sporadic/ spontaneous- worldwide occurrence * Single animals * Usually older animals ≥8 y in cattle ≥3 y in sheep/ goats * Prions NOT detectable in lymphoid tissue using standard tests Infectivity in lymphoid tissue of sheep (mouse bioassay) Atypical and classical cases have different legal consequences Diagnosis by Western immunoblot or immunohistochemistry

Answer 1077

Classical forms *Uptake of prions mainly via the digestivetract (tonsil, distal ileum) *Spread via the vagusnerve to the CNS and/or haematogenous/ lymphoid spread in smallruminants and cervids *Detection of prions in brain (obex) Spread to periphery (e.g. muscle spindles) Atypical forms*Spontaneous (?) accumulation of prions in brain*Limited spread to periphery although in sheep detectable in distal ileum (after oral challenge) and lymph nodes by mouse bioassay Susceptibility to scrapie dependent on prion protein genotype

Answer 1078

* High susceptibility of VRQ/VRQ sheep with short incubation period * Peripheral prion protein distribution in all VRQ/VRQ sheep * Presence of ARR allele increases incubation period and reduces peripheral distribution

Answer 1079

take brainstem and cerebellum for screening and confirmatory test Screening test: ELISA Fast turn-around time No anatomical context or discriminatory potential *Confirmatory test: Immunohistochemistry, Western Immunoblot WB: no anatomical context, good biochemical discrimination IHC: full anatomical context, good discriminatory potential

Answer 1080

*Slowly progressive neurological disease *Duration: weeks to months (?acute disease) *Usually changes in behaviour, sensation and movement as well asunspecific signs *Lack of association between pathological findings and clinical signs bse- Changes in mental status, behaviour and activity: * Apprehension, fear, nervousness * Dullness may be present in atypical BSE Changes in sensation: * Over-reactivity to external stimuli, startle responses Aversion to touch of the head/ neck Flash test, stick test, clipboard test, bang test/ hand clap Changes in posture and movement * Ataxia, tremor, wide-based stance * Difficulty rising predominant sign in atypical BSE Non-specific signs: * Loss of body weight/condition * Reduced milk yield * Bradycardia * Positive scratch test in atypical BSE (?) scrapie- Abnormal behaviour and mental status -Nervousness/ dullness, bruxism, separation from rest of the flock/ herd *Abnormal sensation Pruritus; over-reactivity to external stimuli less pronounced in sheep Positive scratch test (‘nibble reflex’) *Abnormal movement and posture Ataxia, hypermetria Wide-based stance, crouching (Head) tremor *Other neurological signs Absent menace response, collapsing episodes (narcolepsy?), drooling *Physical changes Loss of weight/ body condition, fleece changes/ wool or hair loss

Answer 1081

Changes in mental status, behaviour and activity: * Apprehension, fear, nervousness * Dullness may be present in atypical BSE Changes in sensation: * Over-reactivity to external stimuli, startle responses Aversion to touch of the head/ neck Flash test, stick test, clipboard test, bang test/ hand clap Changes in posture and movement * Ataxia, tremor, wide-based stance * Difficulty rising predominant sign in atypical BSE Non-specific signs: * Loss of body weight/condition * Reduced milk yield * Bradycardia * Positive scratch test in atypical BSE (?)

Answer 1082

Abnormal behaviour and mental status -Nervousness/ dullness, bruxism, separation from rest of the flock/ herd *Abnormal sensation Pruritus; over-reactivity to external stimuli less pronounced in sheep Positive scratch test (‘nibble reflex’) *Abnormal movement and posture Ataxia, hypermetria Wide-based stance, crouching (Head) tremor *Other neurological signs Absent menace response, collapsing episodes (narcolepsy?), drooling *Physical changes Loss of weight/ body condition, fleece changes/ wool or hair loss

Answer 1083

Changes in behaviour & mental status Separation from herd Loss of fear towards humans Dullness (droopy ears, low head carriage) Teeth grinding * Weight loss * Other signs Hypersalivation, increased regurgitation (risk of aspirationpneumonia) Polydipsia/ polyuria (less frequent in elk) Flaccid hypotonic facial muscles Patchy retention of winter coat in summer Ataxia (more frequent in elk), head tremor Oesophageal distension, ruminal atony Hyperexcitabilitywhen handled Compulsive walking, circling More susceptible to sudden death after handling

Answer 1084

Disease notification (passive surveillance) or positive test (active surveillance) * Cattle Cull of cohort and recent offspring May affect WOAH BSE risk status (currently controlled in GB) Removal of specified risk material at slaughter most important to protect consumer * Sheep/ goats Cull of herd/ flock if BSE Cull of susceptible animals only (classical scrapie) Movement restrictions (classical scrapie) TSE monitoring of animals over 18 months for 2 years

Answer 1085

Non-neuronal cells of the CNS Macroglia- Astrocytes deendrites can be seen on staining and this destingushed them from microglia Form the BBB and control blood flow Microglia- Glial cells Phagocytes Macrophage-monocyte lineage

Answer 1086

Endothelial cells Endothelial cell basement membrane Foot processes of astrocytes fluid going into brain must be tightly regulated

Answer 1087

haematogenous direct extension- nasal, spine, ear retrograde axonal transport

Answer 1088

Thrombotic meningioencephalitis- Calves Histophilus somni- fibrin exudation of the meninges, devistating leasion in gray matter. liquefactive necrosis meninges full of blood and so can be infected this way Cryptococcus- Cats C. neoformans or C. gatti bilateraly asymetrical easions- random Strongylus vulgaris-Horse Coenurus cerebralis Sheep Gid Larval form of tapeworm Taenia multiceps cavetous leasions

Answer 1089

Otitis media- Pasturella multocida fibrotic absess capsua and fluid center Nasal-Aspergillus Ameoba (Balamuthia) very little between nasal sinuses and brain common in dolceocephalic breeds Discospondylitis- infection of intervertable discs Trueperella pyogenes Brucella

Answer 1090

the aetiologica agent travels in the nerve from axon to cell body Listeria monocytogenes From contaminated silage via damage to oral mucosa Travel up cranial nerve to brainstem Unilateral clinical signs- Drooling, facial paralysis Unilateral micro-abscesses Rabies- Family Rhabdoviridae, genus Lyssavirus Zoonotic, notifiable Greatest threat to UK Is seen in wild-ranging bats Furious, dumb, paralytic forms initaly replicates n muscle then acends via retrograde axonal transport in a peripheral nerve via a dorsal root ganglion and then enters the spinal cord and brain

Answer 1091

There are innumerable viruses that affect the nervous system Most typically cause no gross lesions and will have similar histopathological findings possibly- redening of meninges, cerebellar coaning Perivascular cuffing with lymphocytes Several viruses are associated with cerebellar hypoplasia- BVD (cattle) and Bluetongue (sheep and cattle) Feline panleukopenia Swine fever Clinical signs range from Ataxia (kittens) – learn to live with it (altricial or infected as neonates) Opisthonus – incompatible with life (precocial or infected in utero) Several viruses are associated with hydrocephalus, porencephaly and hydrancephalus Seasonal? – consider insect vectors Neurolocalisation- Diffuse? Multisystemic? Abortions? Severe mortality in young animals? Milder flu-like signsin older animals? Behavioural Example: Aujeszky’s disease virus Notifiable Mainly pigs Suid herpes virus- Typical inclusions “Mad-itch” Respiratory, dermal, neuro and repro signs

Answer 1092

increased volume of fluid within the ventricles Typically idiopathic congenital disease In young animals will deform the skull Chihuahuas and other brachys will have to some degree often with no clinical signs. Disease states typically associated with true outflow impedance of the CSF. Head pressing, inappetence, seizures, lethargy and altered mental status Can be seen with BVD

Answer 1093

Loss of cerebral cortical tissue within a cranial vault of normal conformation. The resultant cavity communicates with the ventricular system, and is filled with CSF. Clinical signs may include lethargy, propulsive circling, head pressing, and blindness. Develops as a result of the destruction of developing neural tissues Typically associated with cerebellar hypoplasia and arthrogryposis Worry about Bluetongue, Schmallenberg (and BVD) Akbane virus (not in UK)

Answer 1094

Cystic structures within the neuropil that typically do not communicate with the ventricles Less common Akabane virus, BVD and malignant catarrhal fever

Answer 1095

spread by vector presents with inccorsination, hindlimb weakness spinal cord will apear with asymetric haemorage and necrosis within the grey matter

Answer 1096

Notifiable Mainly pigs Suid herpes virus Typical inclusions “Mad-itch” Respiratory, dermal, neuro and repro signs

Answer 1097

Hydrocephalus = increased volume of fluid within the ventricles Typically idiopathic congenital disease In young animals will deform the skull Chihuahuas and other brachys will have to some degree often with no clinical signs. Disease states typically associated with true outflow impedance of the CSF. Head pressing, inappetence, seizures, lethargy and altered mental status Can be seen with BVD Hydrancephaly Loss of cerebral cortical tissue within a cranial vault of normal conformation. The resultant cavity communicates with the ventricular system, and is filled with CSF. Clinical signs may include lethargy, propulsive circling, head pressing, and blindness. Develops as a result of the destruction of developing neural tissues Typically associated with cerebellar hypoplasia and arthrogryposis Worry about Bluetongue, Schmallenberg (and BVD)

Answer 1098

Teratogenic lesions a Generalised arthrogryposis of the appendicular skeleton (arthrogryposis multiplex congenita) and vertebral column malformation, including torticollis and kyphoscoliosis. b Hydranencephaly, brachygnathia inferior and thickened flat bones of calvarium. Parasagittal section through the head exposing the severely dilated right lateral ventricle

Answer 1099

FOREBRAIN (PROSENCEPHALON) Cerebral hemispheres-Telencephalon Thalamus- Diencephalon Receiving/processing Sensory Information- Auditory Visual Pain Generates movement and posture Role in generating appropriate consciousness/mentatin

Answer 1100

Changes in mentation Changes in behaviour Circling (ipsilateral) Head turn (ipsilateral) Seizures Postural response deficits (contralateral) – NOT WEAKNESS Abnormal nasal mucosal response (contralateral) Abnormal menace response (contralateral) Central Blindness/ Central deafness

Answer 1101

BRAINSTEM Midbrain (mesencephalon) Pons (Ventral metencephalon) Medulla oblongata (myelencephalon) Regulate vital reflex functions: HR, RR, Temperature Cranial nerves and nuclei (CNIII-XII)

Answer 1102

Changes in mentation Changes in behaviour (Respiratory and cardiac abnormalities) Paresis/paralysis- tetra/hemi (ipsilateral) Postural response deficits ( All or ipsilateral one side) Cranial nerve nuclei dysfunction CN III-XII - pupil size - menace response - head tilt - nystagmus - gag reflex - spontaneous or positional strabismus - facial paralysis

Answer 1103

CEREBELLUM-Dorsal Metencephalon Maintain balance and posture and tone Modulates commands to motor neurons

Answer 1104

Intention tremors Hypermetria ( all or ipsilateral), Dysmetria Truncal ataxia broad-based stance Mydriasis Postural response delayed with an exaggerated response ( All or ipsilateral one side) Menace response deficit (ipsilateral) Vestibular dysfunction- head tilt (contralateral), nystagmus, strabismus

Answer 1105

c1-c5 c6-t2 t3-l3 l4-s1 s1-s3

Answer 1106

tetri/hemi paresis/palegia all 4 or one sided ataxia postural reactions reduced in all 4 limbs withdrawl/patellar reflexes normal or increased in all 4 limbs perinela reflex normal normal or increaded limb muscle tone in all 4 limbs normal anal tone Upper motor neuron neurogenic bladder dysfunction other findings- horner syndrome/ respiritory difficulty

Answer 1107

tetri/hemi paresis/palegia all 4 or one sided ataxia postural reactions reduced in all 4 limbs withdrawl/patellar reflexes reduced in one or both tls, normal Pls perinela reflex normal limb muscle educed in one or both tls, normal Pls normal anal tone Upper motor neuron neurogenic bladder dysfunction other findings- horner syndrome/ respiritory difficulty

Answer 1108

para/mono paresis/palegia pls only ataxia postural reactions reduced reduced in one or both Pls withdrawl/patellar reflexes normal tls, normal/increased pls perinela reflex normal limb muscle normal tls, normal/increased pls normal anal tone Upper motor neuron neurogenic bladder dysfunction

Answer 1109

no paresis/palegia no ataxia postural reactions normal withdrawl/patellar reflexes normal perinela reflex normal limb muscle normal normal anal tone lower motor neuron neurogenic bladder dysfunction

Answer 1110

no paresis/palegia no ataxia postural reactions normal withdrawl/patellar reflexes normal perinela reflex normal limb muscle normal normal anal tone lower motor neuron neurogenic bladder dysfunction

Answer 1111

mono, para or tetra paresis/palegia no ataxia postural reactions in one, two or all 4 limbs withdrawl/patellar reflexes in one two ir all 4 limbs limb muscle normal normal anal tone lower motor neuron neurogenic bladder dysfunction other findings- quick onset of muscle atrophy, cranial nerve dysfunction also

Answer 1112

GAIT- Delayed generation, long-strided MUSCLE TONE- Hypertonia SPINAL REFLEXES- Normal to hyperreflexive MUSCLE MASS- Normal, if chronic disuse atrophy POSTURAL REACTIONS- Abnormal/absent

Answer 1113

GAIT- Weak, unable to support weight, short-strided MUSCLE TONE- Hypotonia (Flaccid) SPINAL REFLEXES- Hyporeflexia/areflexia MUSCLE MASS- Normal (maybe abnormal if severe) POSTURAL REACTIONS- Abnormal/absent

Answer 1114

I: Olfactory II: Optic III: Oculomotor IV: Trochlear V: Trigeminal VI: Abducens VII: Facial VIII: Vestibulocochlear IX: Glossopharyngeal X: Vagus XI: Accessory XII: Hypoglossal

Answer 1115

HANDS OFF- BLINDNESS Normal to dilated pupils HANDS ON- Menace response deficit Pupillary Light Reflex deficit

Answer 1116

MOTOR (External) Extra-ocular muscles: Medial rectus Dorsal rectus Ventral rectus Ventrolateral oblique PARASYMPATHETIC (Internal) Sphincter pupillae muscle: Contraction of pupil MOTOR (External) Spontaneous Strabismus (ventral) Abnormal vestibulo-ocular reflex PARASYMPATHETIC (Internal) Mydriasis Absent pupillary light reflex

Answer 1117

Trochlear function: Dorsal oblique Trochlear dysfunction: Lateral rotatory strabismus (cats)

Answer 1118

THREE branches: Ophthalmic: Sensory Maxillary: Sensory Mandibular: Sensory and Motor Sensory deficits: Absent palpebral reflex Medial (ophthalmic branch) Lateral (maxillary branch) Reduced facial sensation Abnormal nasal mucosal response Motor deficits Unilateral: loss of temporalis mass and other masticatory mm Bilateral: dropped jaw

Answer 1119

Function: Lateral rectus muscle Retractor bulbi muscle Dysfunction Medial Strabismus Abnormal Vestibulo-ocular reflex

Answer 1120

HANDS OFF Facial asymmetry Absent movement of ear, eyelid, upper lip and nostrils Drooling Saliva Dropped ear HANDS ON Absent palpebral reflexes Lack of blink in response to menace response and testing facial sensation Dropped lip commissure

Answer 1121

Head tilt Nystagmus: Spontaneous or positional or both Positional ventrolateral Strabismus Vestibular Ataxia Abnormal Vestibulo-ocular reflex

Answer 1122

Reports of dysphagia (IX and X) Reduced/absent gag reflex (IX and X) Inspiratory dyspnoea [laryngeal dysfunction] (X) Regurgitation [Megaoesophagus] (X)

Answer 1123

De-innervation of neck muscles: Sternocleidomastoideus Trapezius Sternocephalicus Brachiocephalicus Atrophy of neck muscles Torticollis?

Answer 1124

Tongue deviation towards the side of dysfunction

Answer 1125

Continuously growing insisors Enamel only on front of insisors omniverous

Answer 1126

Mammary fibroadenima Pituitary tumour Skin tumours- zymbals gland tumour, dermal fibroma/fibrosarcoma

Answer 1127

Most common tumours in mice Mammary tumour- adebicarcinoma Lymphoma/leukemia

Answer 1128

Lymphoma Skin subcutis tumour Mammary tumour

Answer 1129

Hard to tell macroscopically Skin mass or abdominal cell tumours? Species narrows down differentails Cells of origin- Epithelial cell tuour melanoma Spindal cell tumours Round cell tumours Differentials- absess, haematoma, fracture

Answer 1130

Papilloma Squamos cell carcinoma Trichofolliculoma- from hair follicle Tricopitheliomoa- from hari follicle Scent gland tumours Mammary tumour

Answer 1131

Papilloma- benign Common Single or multiple Exophytic/ polupoid Viral origin possible Squamous cell carcinoma- Less common Often ulcerated

Answer 1132

Trichofolliculoma- Most common epithelia tumour of guinie pigs Benign Solitary, dome shaped, firm subcutaneous nodules, <2cm Central pore with keratien debris Common in dorsal lumbar region Trichoepithelioma Common in hamsters Associated with poluoma virus infection Common on face-lips pinna, ear canal neck Discrete, well circumscribed Multiple and cystic

Answer 1133

Modified sebaceous glands Ventral abdomen in gerbals, flank in hamsters Hyperplasia ad sebaceous and squamous cell neoplasms Benign or malignant

Answer 1134

Fibroadenomsa Benign Wel demarcated in subcutis May have underlying pituitart tumour

Answer 1135

Tend to be more glandular More likely malignant- adenocarcinoma Do metastisise esp in mice

Answer 1136

Lipoma Liposarcoma Fibroma Fibrosarcoma/spindle cell sarcoma Microchip related sarcoma

Answer 1137

Common in guinea pigs Usually well circumscribed Soft,fluctulant

Answer 1138

Firmer than lipoma Subcutaneous masses Spindle shaped cells Viriable collagen and mitotic activity Metasteses uncommon eve with malignant tumours

Answer 1139

Hamsters and rodents Face, ears, neck, feet Dark irregular mass Can metastisise

Answer 1140

Masses- often equate to affted lympnodes- groun, axilla, neck Lymphoma may just aft lymphnodes or include other organs In hamsters- epitheliotic lymohoma- alopecia and scalling

Answer 1141

Osteosarcoma- mice Haemangiosarcoma- mice Hibernoma- rats Malignant fiberous histiocytoma Histiocytic sarcoma Zymbals gland tumour not particularly common

Answer 1142

Cysts Pyogranulomas Absesses especially in sebaceous gland- Cliterola Zymbals gland

Answer 1143

Head or jaw From fighting or trauma Typicallu pyogranulomas Gram +ve cocci ususally

Answer 1144

Rodents Modified sebaceous gland at base of ear Common site for absess formation Can present as otitis externa Ddx tumours

Answer 1145

Indications Suspected inflammatory or neoplastic lesions of the central nervous system Contraindications Atlanto-occipital collection contraindicated if signs of brain herniation are present. Advantages Findings often highly significant and of good diagnostic and prognostic value. Disadvantages Results of analysis may be unrewarding or non-specific. Need for general anaesthesia. If dramatic drop in CSF pressure created during withdrawal of CSF, this may result in tentorial herniation and convulsions.

Answer 1146

lumbar cistern cereblomedullary cistern

Answer 1147

total nucleated cell count (TNCC) red blood cells (RBC) total protein (TP) concentration cytological evaluation. Normal CSF does not contain RBC and has a TNCC of less than 5 cells/μL. CSF TP concentration should not exceed between 25–30 mg/dL at the cerebellomedullary cistern and 45 mg/dL at the lumbar subarachnoid space CSF can also be tested with PCR for infectious diseases Neospora

Answer 1148

pugs and yorkshire terries have idiopathic inflamatory diseases tap shows massive amounts of inflamitory cells some involve high numbers of eosinophils- eosinophilic meningitis steriod responsive meningitis arteritis involves high no of neutrophils in csf

Answer 1149

can see metastatic carcinoma- cels displaying adhearence and malignant criteria. not often epithelil tumours in spinal cord so is a metastisis lympoma can be seen

Answer 1150

increased number of macrophages containing material- possibly myelin

Answer 1151

macrophage with globules in cytoplasm that pick up staining

Answer 1152

Pathogenesis: Reduced number or function of nicotinic acetylcholine receptor Acquired: aberrant immune process results in development of autoantibodies produced against the nicotinic acetylcholine receptor Congenital: mutations in choline acetyltransferase gene, acetylcholine esterase collagen gene or the receptor itself Pathophysiology: Due to a lack of communication from the nervous system to muscle. Clinical signs: Weakness, dysphagia, regurgitation (mega-oesophagus). Diagnosis Rule out a myopathy- Creatine kinase (CK) Response to edrophonium chloride (Tensilon test)- Inhibits the enzyme acetylcholinesterase Weakness should improve within 30-60 seconds, with effect persisting for 3-5 minutes Serology for AChR antibodies Thoracic radiography can be caused by thymic mass

Answer 1153

Pathogenesis: Loss of sympathetic innervation to the globe and adnexal structures. Pathological change at one of several sites: First order: brain stem to T1-T3 spinal cord lesions. Second order: (pre-ganglionic fibers) arising in spinal cord segments T1-T3 and joining the vago-sympathetic trunk via the rami communicators. Third order: (post-ganglionic fibers) arising at cranial cervical ganglion rostrally joining the trigeminal nerve at the trigeminal ganglion. Pathophysiology and clinical signs: reduction of sympathetic nerve supply to smooth muscle of orbit third eyelid protrusion, ptosis, miosis Underlying cause differs between species Canine = idiopathic Feline = otitis media/nasopharyngeal polyip/iatrogenic Equine = guttural pouch disease Also seen with grass sickness (see later) Diagnosis 1% phenylephrine applied topically to both eyes- mydriasis in the affected eye with no response in the control eye Cats – head radiography or CT Horse – scope guttural pouch versus imaging of the neck depending on other clinical signs/history

Answer 1154

Equine dysautonomia Pathogenesis Degeneration of autonomic neurons in the brain, ganglia, and enteric nervous system Due to Clostridium botulinum toxin Signalment- Adult horses at grass Clinical signs- Tachycardia, ileus, colic Chronic weight loss Acute colic and gastric reflux Bilateral Horner's syndrome Diagnosis- Histo Biopsy of rectal or ileal samples in live animals Cranial mesenteric or cranial cervical ganglion post mortem Chromatolysis

Answer 1155

atrophy of the temporal muscle symetricaly due to imuune system attaching the muscle

Answer 1156

Results in back up of blood as right side cannot receive it properly and so results in Congestion of peripheral tissues- Dependent oedema and ascites- blood ooses from vena cava- Transudate fluid Liver congestion- signs related to impaired liver function Gi tract congestion- anorexia, gi distress, weight loss

Answer 1157

Results in decreased cardiac output as left ventricle cannot pump blood- Activity intolerance, signs of decreased tissue perfusion Inability of left atrum to receive blod results in Pulmonary congestion- Impaired gas exchange- cyanosis and signs of hypoxia Pulmonary odema- cough with frothy sputum, orthopnea, paroxysmal nocturnal dyspnea

Answer 1158

Congenital heart disease (CHD) refers to a group of heart conditions that are present at birth in animals. CHD is relatively common in veterinary medicine, and it can affect many different species of animals. Examples include Ventricular septal defect (VSD): A hole in the wall that separates the two lower chambers of the heart. Atrial septal defect (ASD): A hole in the wall that separates the two upper chambers of the heart. Pulmonic stenosis: Narrowing of the valve or artery that leads from the right ventricle to the lungs, which can lead to reduced blood flow to the lungs. Patent ductus arteriosus (PDA): A blood vessel that fails to close after birth, leading to abnormal blood flow between the aorta and pulmonary artery. Tetralogy of Fallot (TOF): A combination of four heart defects, including a ventricular septal defect, pulmonary stenosis, an overriding aorta, and right ventricular hypertrophy. Vascular ring anomalies such as persistent right aortic arch

Answer 1159

The most commonly reported CHD in cattle Also seen in cats and miniature swine, occasionally in dogs- Heritable in English Springer Sps Typically located in the perimembranous portion of the septum- high in the ventricular septum Left to right shunting of blood- he pressure in left ventricle higher than right, too high pressure for right ventrile so blood flows back into pulmonary vessel-> pulmonary hypertension

Answer 1160

In the foetus, the atria are connect by the foramen ovale which closes at/ shortly after birth. Failure to close (patent foramen ovale) is not the same as true ASD, which is due to a true hole in the interatrial septum- can teel difference as in asd the scarring form the patent foramen ovale should be to the right Left to right shunting- Less blood can come in from vena cava so backs up-> right-sided heart failure= ascites

Answer 1161

Overrepresented in brachycephalic dogs such as Bulldogs, but also JRTs, Labradors and Samoyeds Fusion or dysplasia of the pulmonic valve leaflets May cause thickening of right side of heart as it eeds to work harder to force blood past stentic gap-> Right-sided heart failure

Answer 1162

The most common CHD of dogs In the foetus, the Ductus arterious shunts blood from Pulmonary Artery to aorta so as to bypass the lungs After birth failure to close results in Aota to Pulmonary Artery shunting-> oxygenated blood that is intended for body goes to pulmonary arter- less oxygenated blood in body- pressure in lungs as they are overwhelmed with amount of blood->-> pulmonary hypertension and LHS failure Results in base murmer

Answer 1163

PRAA not a true CHD as involves vessels outwith the heart As a foetus, most structures develop symmetrically, this is true also of vessels of the heart with unnecessary duplicated structures regressing. The aorta should curve to left of trachea- in an animal with PRAA, the right fourth arch, instead of the left, becomes the functional aorta. The ligamentum arteriosum (LA) extends between the left pulmonary artery and the anomalous Right Aortic Arch, causing constriction of the oesophagus causing megaoesophagus

Answer 1164

PRAA not a true CHD as involves vessels outwith the heart As a foetus, most structures develop symmetrically, this is true also of vessels of the heart with unnecessary duplicated structures regressing. The aorta should curve to left of trachea- in an animal with PRAA, the right fourth arch, instead of the left, becomes the functional aorta. The ligamentum arteriosum (LA) extends between the left pulmonary artery and the anomalous Right Aortic Arch, causing constriction of the oesophagus causing megaoesophagus

Answer 1165

compared to dogs, which primarily have breathing issues, is a blocked nasolacrimal duct.

Answer 1166

Watery eyes= epiphora May have purelant discharge Inflammation and infection of the duct= dacryocystitis Also more prone to malocclusion

Answer 1167

Disease of rabbits Aetiological agent Pasturella multocida Pathology Rhinitis -> turbinate atrophy Pneumonia Abscesses Otitis media -> head tilt

Answer 1168

Pneumonia-Pseudomonas spp, Bordetella bronchiseptica, Staphylococcus spp, and Streptococcus have also been isolated Carriers of P. multocida can be identified by an indirect fluorescent antibody test on nasal swabs. Common comensal An ELISA test to detect antibodies against P multocida may also help detect carriers. It is important to remember that Pasteurella can be sampled from a large percentage of clinically normal rabbits, and culture results must be interpreted carefully PCR can discriminate between different isolates and is commercially available.- Not every strain of Pasteurella is pathogenic. Five serotypes (strains) of Pasteurella have been described, with two of them most commonly involved in pathologic conditions in rabbits. Pathology of cranial ventral lesion of lung lobe Seropuralent discharge from nose Abcesses in lung lobes

Answer 1169

The most common neoplasia of the rabbit reproductive tract and probably the most common neoplasia of any body system of female rabbits Carcinoma = malignant 80% will metastasize lungs

Answer 1170

Bordetella bronchiseptica and Pasteurella multocida Bordetella phase- Virulence factor: Dermonecrotic toxin (DNT) Pasteurella phase- Virulence factor Pasteurella multocida toxin (PMT) Pathogenesis and pathophysiology: DNT Kills epithelial cells allowing access of PMT to submucosa PMT Increases osteoclasts and inhibits osteoblasts-> turbinate atrophy

Answer 1171

Enzootic pneumonia (EP) is the most common respiratory disease seen in pigs in the UK.- Mycoplasma hyopneumoniae The primary agent of the porcine respiratory disease complex (PRDC) PRRSV, PCV2, Swine influenza virus, Pasteurella multocida, Actinobacillus pleuropneumoniae, Haemophilus parasuis, Bordetella bronchiseptica Other influencing factors are housing conditions and management practices (like crowding, poor air quality, stress) Pig specific Present in more than 80% of pig herds in the UK Clinical signs 3-5months Low-grade to severe cough Mild fever Slowed growth Secondary more sever infections Gross lesions- Classic bilateral cranioventral Histo- Bronchopneumonia Diagnosis- Mycoplasma spp are difficult to culture - PCR

Answer 1172

Bordetella bronchiseptica Pastrurella multocida

Answer 1173

Bordetella bronchoseptica Pasturella cultocida Prrsv Pcv2 Swine influenza virus Actinobacillus pleuropneumoniae, Haemophilus parasuis,

Answer 1174

Actinobacillus pleuropneumoniae Clinical signs- fever, anorexia, reluctance to move, respiratory distress, and sudden death Gross lesions- severe fibrinonecrotic and hemorrhagic pneumonia with accompanying fibrinous pleuritis and/or pericareditis Diagnosis- culture

Answer 1175

Actinobacillus pleuropneumonaie

Answer 1176

mycoplasma hypopneumoniae

Answer 1177

Glaesserella (Haemophilus) parasuis Fibrinous polyserositis and polyarthritis, but septicemia with sudden death and bronchopneumonia also can occur Diagnosis- Bacterial culture or PCR

Answer 1178

Glaesserella parasuis

Answer 1179

Implicated viruses- PRRSV (porcine reproductive and respiratory syndrome virus) Coronavirus Swine Influenza virus Circovirus (PCV2) Inhaled- Contribute to cranioventral lesions in association with bacterial bronchopneumonia More typical of viral pneumonia is INTERSTITIAL PNEUMONIA

Answer 1180

Sneezing, coughing and difficulty breathing Abortions (in some cases) Nasal and ocular discharge Pyrexia Loss of appetite Weakness swollen and red eyes

Answer 1181

disease of pigs Due to vitamin E/selenium deficiency- Anti-oxidants Cardiomyocyte and vascular necrosis- Polyphasic Important differential for cardiac necrosis in pigs are viruses in the picornavirus family- Foot and Mouth Disease Virus

Answer 1182

The most frequent heart disease in cats is hypertrophic cardiomyopathy (HCM) Heritable in Bengals, British Shorthair, Maine Coon, Persian, Ragdoll, and Sphynx cats Proven genetic basis in Maine Coons and Ragdolls- Myosin binding protein Diastolic failure- Inability of the left ventricle to relax and therefore fill fully Due to areas of fibrosis and left ventricular hypertophy Pulmonary oedema Pleural effusion Heart weight >20g LV and IVS thickened Dilated left atrium Thrombus in left atrium Thromboembolism in aortic trifucation

Answer 1183

Taurine deficiency Making a come back thanks to weird diets

Answer 1184

Genetic- Doberman Pinschers, Boxers, Great Danes, German Shepherd Dogs, Irish Wolfhounds, Scottish Deerhounds, Newfoundlands, Saint Bernards, and Labrador Retrievers Dietary- Taurine Gluten free? Doxorubicin Parvo Insidious combination of left and right sided failure Systolic failure

Answer 1185

Boxers Rarely in cats Genetic defect- Striatin Syncope and sudden death Arrythmia

Answer 1186

Myxomatous Atrioventricular Valve Degeneration CKChSp massively over-represented Cause unknown Fibrous layer of the mitral valve undergoes myxoid degeneration Leaky valve results in back flow of blood into left atrium Left sided heart failure

Answer 1187

Bacterial endocarditis arises from adhesion of the microorganisms to the endocardium, leading to death of the endothelium and formation and adherence of a thrombus within which large colonies of bacteria proliferate. Streptococcus sp., Staphylococcus sp. and E. coli are frequently implicated as the etiologic agents in many species. Additionally, Erysipelothrix rhusiopathiae is often isolated in pigs and (occasionally) dogs, while Bartonella sp. is more specific to the dog or the cat. Arcanobacterium pyogenes is a common pathogen in cattle and Actinobacillus equuli can occasionally cause valvular endocarditis in horses. Look for the underlying cause IV catheter?

Answer 1188

The sac around the heart can fill with fluid for several reasons The most common PE in dogs would be haemorrhagic and due to a ruptured haemangiosarcoma PE is rare in cats but most commonly associated with heart failure In sheep a transudate/modified transudate with fibrin clots is most indicative of Clostridium perfringens type D Fibrinosuppurative pericarditis in cattle is secondary to penetration of a wire from the stomach All will impede function of the heart due to compression Cardiac tamponade Right side most vulnerable

Answer 1189

IMPORTANT – influenza virus not involved! Multifactorial: Viruses-Herpes Calicivirus Bacteria- Chlamydophila/Chlamydia felis Bordetella bronchiseptica Mycoplasma felis also Polyps- cause of polyps is a little unclear but we presume it is a proliferative response to chronic infection or inflammation, for example chronic otitis Clinical signs- Rhinitis, sinusitis, conjunctivitis Pneumonia rarely

Answer 1190

The most common non-dermal fungal disease of cats C neoformans or C gattii From pigeon faeces Zoonotic Asymptomatic airborne colonisation of the respiratory tract Nasal form most common Cutaneous, systemic (including ocular) and CNS forms all reported Cytology - Classic yeast form with virtually pathognomonic thick capsule

Answer 1191

Aelurostrongylus abstrusus Relatively rare compared to canine lungworm

Answer 1192

Pleuritis (pleurisy) is inflammation of the pleural cavity Thoracic empyema/pyothorax is the accumulation of pus in the pleural cavity Bite wound? Typically polymicrobial- Escherichia col Pasteurella spp. Actinomyces spp. Nocardia spp. Streptococcus spp. Staphylococcus spp. Corynebacterium spp. 62% survival?

Answer 1193

Allergic lower airway disease Key clinical sign is coughing- Cats with heart failure do not cough c.f. dogs Inspiratory wheeze- Marked effort on inspiration Overinflated/flattened diaphragm Bronchoalveolar lavage- eosinophils

Answer 1194

Pulmonary adenoma/carcinoma Seen in all species Pulmonary adenocarcinoma relatively common in aged cats Pulmonary adenocarcinomas in the cat most commonly metastasize to the digit- Lung-digit syndrome Goblet cells and cilia in a toe tumour!

Answer 1195

‘Snotty nose’ is a common presentation, particularly in communal yards Clinical Signs- Bilateral, mucoid/mucopurulent nasal discharge Snorting/URT stertor/coughing Aetiology Viral: Herpes (EHV1 or 4) Equine rhinitis A & B viruses (Picornaviridae) Adenoviruses Bacterial: Normally secondary infection- Strep. equi zooepidemicus Treatment Usually none required – 1st line antimicrobial therapy only if absolutely necessary URT Viral infection Altered mucociliary clearance-> mucoid discharge (Obstruction to drainage Cyst / Neoplasia Trauma) Stagnation of mucus within sinus Secondary bacterial infection -> purulent discharge (Dental Disease Accumulation of pus (empyema)

Answer 1196

Objectives of therapy Total remove infection / diseased tissue Restoration of normal drainage and mucociliary clearance Prevent recurrence 1o - Acute/uncomplicated-Antimicrobials – TMPS or Penicillin Mucolytics & Controlled exercise 1o - Chronic- + sinus trephination and regular lavage 2o – Dental, trauma, neoplasia- + treatment/removal of inciting condition

Answer 1197

The roots of the maxillary molar cheek teeth lie within the maxillary sinus space Covered by very fine layer of alveolar bone and sinus periostium Apical tooth root infections of these teeth will result in sinusitis Less profuse but often malodourous nasal discharge Chronic sinusitis, non-responsive to medical Tx Must examine the oral cavity / occlusal surfaces of teeth to assess for any pathology. Radiographs are usually diagnostic

Answer 1198

Can occur in horses of any age 3rd most common sinunasal disorder Large expansile structures which can distort nasal structure Clinical signs Serous/Mucoid unilateral nasal discharge Facial distortion(maxillary or frontal) Obstruction to nasal airflow Abnormal respiratory noise Treatment >90% success rate with extirpation via sinus flap surgery

Answer 1199

Frontal sinus or the caudal maxillary sinus Placement of a indwelling foley catheter Allow high volume lavage and instillation of antimicrobials

Answer 1200

Better surgical access to sinuses Improve drainage; Breakdown bullae CMS  RMS Create ventral fistula between MS and middle meatus

Answer 1201

Non-neoplastic Progressive sub-mucosal haemorrhages Can develop in nasal or sinus portion of ethmoids Intermittent epistaxis (altered/ ‘mucky’ blood) Varying degrees of nasal/sinus obstruction Treatment Small lesions: Intralesional formalin Large lesions: Surgical resection via sinus flap Prognosis- Fair High rate of recurrence

Answer 1202

Clinical Signs- Initial Fever Inappetance Dull, lethargy 2nd fever URT obstruction Dyshpagia Discharge Fomitic spread of infected material-Inhalation or ingestion of S. equi Colonisation of URT epithelium/tonsil tissue-2-6d Incubation period Rhinitis and pharyngitis Spread to local lymphatics- Submandibular, retropharyngeal, parotid. Systemic bacteraemia can occur-Seeding in distant lymphatic tissue Lymphadenopathy & Abscess formation-GP Empyema, Abscess rupture diagnosis- Sample sites Nasopharyngeal swabs Purulent discharge Guttural pouch lavage- detects carrier horse To confirm disease History and clinical signs Culture + qPCR on any of above To confirm resolution or ID carrier qPCR on 3 sequential NP swabs qPCR on 1 NP swab and GP lavage Analysis methods: Bacterial culture Can have false positives Quantitative PCR analysis (qPCR) Better sensitivity and specificity Supportive therapy during acute phase of infection; Nursing support Non-steroidal anti-inflammatory medication-Flunixin meglumine, 1.1mg/kg IV or PO BID Encouraging drainage of abscesses- Hot pack, surgical lancing, daily cleaning/lavage Antimicrobial therapy Reserve for very sick/compromised patients. S. equi equi usually sensitive to Penicillin (20-25mg/kg IM BID)  will have benefit in early disease, but may interfere with development of natural immunity

Answer 1203

Inflammation/infection of GP Prone to the same pathophysiology for infection as the sinuses Clinical signs similar to GP mycosis, +/- purulent discharge Chronic empyema _> chondroid formation Treatment - Removal of inspissated material - Lavage and topical antibiotic Crystalline penicillin admixed with gelatin instilled into gutturall pouch Any horse with purulent material in the GP should be tested for Strep. equi equi infection GP’s are a predilection site for strangles Close association with lymphatic structures of the URT (retropharyngeal LN’s)

Answer 1204

Aspergillus (e.g. A. fumigatus) - Opportunistic infection Presence of fungal plaques on the GP mucosa Predilection sites over the Internal (ICA) or External ECA) carotid arteries Clinical Signs Depend on location of fungal plaque, and degree of local tissue damage/inflammation; Erosion of ICA or ECA- Epistaxis initially intermittent, progressing to possible exsanguination Mucosal Only- No clinical signs Mild, intermittent mucoid discharge Cranial nerve dysfunction- Pharyngeal paralysis Laryngeal hemiplegia Facial paralysis Horner’s syndrome Pain in parotid region Stiffness in the neck Reduced appetite Diagnosis- History of repeated episodes of unilateral epistaxis Endoscopy – Cautious examination of the GP Treatment- Medical management with systemic or topical anti-fungals is rarely successful- Only for sub-clinical cases Where there is evidence of haemorrhage, horse should be referred for ligation of the internal carotid artery- Need to occlude artery distal and cranial to the lesions Prognosis- Guarded – Complications are common Poorer prognosis if significant neurological dysfunction present

Answer 1205

The RLn contains the longest motor axons in the horse, measuring up to 2.5 m in length in Draft and Thoroughbred horses, with the left nerve being30 cm longer than the right in tall breeds Left rln occurs more than right URT Obstruction Causes marked inspiratory effort Dynamic collapse of soft tissues due negative pressure associated with inspiration Inspiratory STRIDOR or STERTOR treatment- Ventriculectomy Ventriculocordectomy Laryngoplasty Arytenoidectomy Neuromuscular pedicle graft

Answer 1206

Syndrome of mature horses. Generally > 7-years-old A condition of small airway obstruction characterised by; Neutrophilic inflammation (bronchiolitis) Mucus hyper-secretion Bronchoconstriction / Bronchospasm Previously known as Equine Heaves, COPD Allergen induced hypersensitivity response; Commonly associated with stabling – high exposure to allergens- Poor environment, ventilation and management can all contribute Summer Pasture-associated RAO – induced by environmental pollens respiritory pattern- LRT Obstruction Thickening, inflammation and mucus Causes increased expiratory effort Small airways held open during inspiration Early collapse during expiration Acute condition is reversible with; Removal of inciting cause / Environmental management Medical therapy- Bronchodilators, Anti-inflammatories (corticosteroids) Chronicity can result in irreversible change; Metaplasia of epithelium Permanent obstruction Alveolar over-inflation -> emphysema Bronchovesicular sounds- Increase airflow  Harsh intensity Wheezes - Air passing through narrow airways- Bronchoconstriction Crackles/Rales - Air passing through fluid & mucus

Answer 1207

Can affect any age of horse, but more common in younger horses Multifactorial (or multiple aetiologies proposed) - Non specific inflammation: Neutrophilic, eosinophilic or mast cell-associated Post-viral infections Bacterial aetiology Parasitic involvement Secondary to pulmonary haemorrhage Very often sub-clinical when at rest Common clinical findings Exercise intolerance and poor performance Intermittent cough associated with exercise Varying degrees of mucus accumulation

Answer 1208

BAL fluid cytology Specific and informative neutrophilic response Medical therapy For clinical RAO, or IAD when associated with poor performance BRONCHODILATORS Anticholinergics Atropine- Very effective when given IV for acute episodes Hyoscine butylbromide- Potent and rapid bronchodilatory effect Ipratropium - Given as inhalational therapy Β2-agonists Clenbuterol-Bronchodilator, anti-inflammatory and improves mucociliary clearance Salbutamol/Albuterol -Inhalataional therapy Medical therapy For clinical RAO, or IAD when associated with poor performance CORTICOSTEROIDS Oral/systemic Prednisolone- Only licensed oral steroid in horses Dexamethasone- More potent than prednisolone Inhalational Beclomethasone, Fluticasone Both have more potent anti-inflammatory action and reduced systemic side effects Systemic- Acute exacerbations Establish ‘control’ of allergy Restore normal function Inhalational- Better for long term control Minor relapses Can tailor treatment to response Environmental Management Essential in the treatment of any form of lower airway inflammation Maximise time at pasture Reduce exposure to dust / spores Dust extracted bedding – keep clean Avoid hay where possible- Feed haylage , Soaking or steam hay Optimise ventilation when indoors/ stabled Turn horse out before mucking out Stable away from muck heap or busy thoroughfares May require change of location / yard

Answer 1209

Infectious canine tracheobronchitis = Canine infectious respiratory disease (CIRD) complex Infectious tracheobronchitis that is usually self-limiting unless complicated by bronchopneumonia in unvaccinated pups or old/immunosuppressed dogs Frequently involving several infectious agents: Canine parainfluenza virus (CPIV) Canine adenovirus type 2 (CAV-2) Canine herpesvirus (CHV-1) Bordetella bronchiseptica Mycoplasma canis and M. cynos Usually apparent 3-7 days after exposure Cough (dry or productive), retching - particularly during exercise and when on lead Nasal +/- ocular discharge, sneezing In most cases recovery after one to three weeks Pathogenesis- Infection of respiratory epithelial cells by viruses and/or Bordetella Cell damage caused by viruses and bacterial toxins Inhibition of ciliary clearance by damage to ciliated cells Potential secondary bacterial infections (streptococci, Pasteurella spp.) Different mix of infectious agents may produce same clinical signs

Answer 1210

Causes mild respiratory disease Frequently (>50% cases) isolated from dogs with respiratory disease More severe disease if in combination with Bordetella

Answer 1211

CAV-2 causes respiratory disease Not commonly associated with kennel cough in UK/US possibly due to good adenovirus vaccine uptake CAV-1 causes hepatitis (ICH) (but has been reported to cause respiratory disease as well)

Answer 1212

DNA virus – IN eosinophilic IBs fatal systemic disease in young puppies (< 2wks old) ‘fading puppy syndrome’ thermotropic virus (<35.5oC) mild tracheobronchitis in adults (part of ‘kennel cough’ complex) Multifocal necrotising hepatitis with eosinophilic intranuclear IBs (also necrotising nephritis)

Answer 1213

Small Gram-negative rods Main phenotypic traits Motile Strict aerobe Glucose non-fermentative Oxidase-positive Commensal of the upper respiratory tract Endogenous or exogenous infection transmitted by aerosol or direct contact Diagnosis by PCR or culture Treatment: doxycycline or amoxicillin with clavulanic acid Intranasal multivalent vaccines

Answer 1214

Associated with mild respiratory disease Highly contagious Vaccine under development (RVC/Zoetis) Distinct from canine enteric coronavirus (CECoV) (mild diarrhoea in young dogs) CECoV vaccines do not cross protect

Answer 1215

Discovered in 2010 in NE USA while looking for novel respiratory viruses in animal shelters Closely related to murine pneumovirus and human respiratory syncytial virus (RSV) More recently been isolated from non-shelter dogs Often co-infections with other respiratory viruses RVC involved in a large prevalence study (early data ~25-60% +ve, 93% have Abs)

Answer 1216

All segments of viral genome derived from equine influenza Direct transfer of equine virus rather than reassortment Spread within the canine population by dog to dog contact (droplets, aerosols) Evidence for presence of influenza virus in subsequent outbreaks of non-fatal respiratory disease at race tracks and dog shelters across North America and a small numbers of UK reports in foxhounds Vaccine now licensed in USA H3N2 now likely endemic in US shelters Serological studies in UK pet dogs so far negative

Answer 1217

Canine distemper virus (CDV), a morbillivirus (related to measles) Shed in all body fluids Spreads by aerosol or close contact Nasal and ocular discharge, cough Diarrhoea, vomiting Depression Anorexia Virus enters via the respiratory tract Spreads to tonsils and local lymph nodes Infects monocytes/macrophages Viraemia, systemic dissemination 2-3 weeks after infection dogs which are able to develop a good humoral and cellular immune response will recover or develop a mild form of the disease In dogs with insufficient immune response CDV spreads to epithelial cells of the respiratory, gastrointestinal and genitourinary tract as well as the CNS CDV causes immunosuppression  secondary bacterial infections

Answer 1218

LRT bacterial pathogens in dogs Small Gram-negative rods (coccobacilli) Main phenotypic traits: Non-motile Facultative anaerobe Glucose fermentative Oxidase-positive Commensal of oral cavity and URT Opportunistic pathogen associated with: Secondary URT infections (>pets) Secondary LRT infections (>cattle) Bite infections in pets and humans Usually susceptible to penicillin No effective vaccines

Answer 1219

LRT bacterial pathogens in dogs Gram-positive cocci in chains Main phenotypic traits: Non-motile Facultative anaerobe Glucose fermentative Catalase-negative Commensal on respiratory mucosae Two species associated with pets S. equi subsp. zooepidemicus S. canis Opportunistic pathogens that cause suppurative infections, including outbreaks in kennels Susceptible to penicillin

Answer 1220

Severe suppurative pneumonia and pleuritis (pyothorax/empyaema) Important in cats following bites or other infected wounds Often part of mixed infections

Answer 1221

Commensal in the URT of horses (mainly associated with abortion/low-grade URT dz) In recent years increasingly reported in dogs Between 2006-7 a pathologist in California reported on an outbreak involving over 1000 dogs in a single kennel. These dogs had either suffered from or died of haemorrhagic pneumonia caused by a single clone of S. zooepidemicus Pyrexia, haemorrhagic nasal discharge and sudden death PM: severe necro-haemorrhagic and fibrino-suppurative bronchopneumonia

Answer 1222

Rare infections in dogs caused by Actinobacteria, a diverse group of Gram-positive bacteria that grow slowly and produce branching filaments. Two species involved: Actinomycetes viscosus: commensal in oral cavity of dogs. It can cause chronic pyogranulomatous lesions on the pleura (often associated with pyothorax) or other organs (e.g. cutaneous forms after bite wounds). The main clinical sign is respiratory distress. Usually responsive to penicillin. Nocardia spp. (e.g. N. asteroides): soil bacterium that cause thoracic as well as cutaneous and disseminated forms. The clinical picture is the same as for actinomycosis but the organism is acid-fast and resistant to penicillin due to the wax-like mycolic acids in the cell wall. Sulfa TMP is one of the antimicrobials indicated for treatment of nocardiosis Copious red-brown exudate in pleural cavity May become chronic with adhesion formation Exudate contains ‘sulphur granules’

Answer 1223

Disease caused by Aspergillus fumigatus, a fungus inhabiting soil and decomposing organic matter Acquired by inhalation of spores Two types of infections in dogs (other animals may also be affected): Nasal aspergillosis: invasive sinusitis with persistent and profuse sanguino-purulent nasal discharge (usually unilateral). Systemic aspergillosis: this form occurs in immunosuppressed animals and clinical signs depend on location of the pathogen. Treatment is difficult (bad prognosis). Rapidly growing (2-3 days) on Sabouraud Dextrose agar (medium used for fungal culture, low pH (5.5) plus antibiotics to inhibit bacterial growth) Nasal turbinates progressively destroyed by chronic (pyo)granulomatous (and eosinophilic) inflammation There may be a yellow-green mycotic exudate in the caudal nasal cavity

Answer 1224

Dictyocaulus viviparus Life cycle: 4weeks ppp The life cycle is similar to that of the gastrointestinal nematodes except that eggs, containing first-stage larvae (L1) are coughed up and swallowed and then hatch during passage through the digestive tract. The L1 present in freshly-voided faeces, are characteristically sluggish and their intestinal cells are filled with dark brown food granules. The pre-parasitic stages do not need to feed. Under optimal conditions the L3 stage is reached within 5-7 days, but this may take longer depending on the environmental conditions. The L3 leave the faecal pat to reach the herbage through their own movements or by airborne spread utilizing the fungus, Pilobolus. After ingestion, L3 penetrate the intestinal mucosa and pass to the mesenteric lymph nodes where they moult. The L4 then travel via the lymph and blood to the lungs, and break out of the capillaries into the alveoli about one week after infection. These migrate up the lungs and moult to L5, becoming mature adults between three and four weeks after infection, when L1 can be detected in dung. The adults are found in the main stem bronchi and trachea. Clinical signs: Youngstock during their first grazing season on permanent or semi-permanent pastures, from late summer-early autumn. Characterised by bronchitis and pneumonia Deep husky cough, worse after exercise. Which varies with the severity of the infection. Stand with head and neck outstretched ‘air hunger position’. Respiratory rate >80 bpm. Bright, alert and feeding, however lose condition rapidly. Expiratory dyspneoa and death can occur in heavy infections where there is massive obstruction of the airways. Auscultations: harsh inspiratory and expiratory noise. Moist rasps as fluid accumulated, loud breath sounds and crackles over the bronchial tree (ventral lung consolidation) crackles over the dorsal diaphragmatic lobe (dorsal interstitial emphysema). Diagnosis: History (movement, pastures), clinical signs, auscultation. Baermann technique faecal test-confirms lungworm infestation (see L1). Not all animals will shed larvae if they are int eh early stages of disease whilst the worms are immature. So absence of L1 does not exclude parasitic bronchitis from a differential diagnosis list. Bronchoalveolar lavage or sputum examination for eosinophils, eggs, larvae is a sensitive method of diagnosis. Serological or bulk milk ELISA antibody test are available in some parts of the world, however bulk milk samples may have a low sensitivity. Post mortem Baermann and ELISA prone to false negatives! So always be mindful of the history and clinical signs Gross pathology: lesions: large, grey, depressed, wedge shaped areas of atelectasis present usually along the dorsocaudal aspect of the lungs. Reginal lymph nodes enlarged. On the cut surface: oedematous foam and mucus mixed with white, slender (up to 80mm long) nematodes in bronchi. In the most severe cases, massive numbers of nematodes fill the entire bronchial tree. Microscopically: parasite in bronchi are associated with excess mucus due to goblet cell hyperplasia, metaplasia of bronchial and bronchiolar epithlium, alveolar oedema, hyperplasia of BALT, hyperplasia of bronchiolar smooth muscle and a few eosinophilic granulomas around the eggs and dead larvae. These granulomas , grossly, are grey nodules (2-4mm) and may be confused with those caused by tuberculosis.

Answer 1225

is an acute allergic reaction (full aetiology unknown). It occurs when previously sensitized/immune adult cattle are exposed to large numbers of larvae. Many larvae are killed on reaching the bronchioles by the animals immune response. A large larval challenge may induce a severe and often fatal immune-mediated hypersensitivity reaction. Lesions are of a hypersensitivity pneumonia Clinical signs of severe respiratory distress, expiratory dyspnoea, oral breathing, pneumonic emphysema and subcutaneously on the back. Diagnosis: disease does not become patent as the parasite is killed in the lungs so there will be no larvae in the faeces (Baermann test not useful). Low/no antibody response (ELISA not useful either) Gross lesions include diffuse interstitial pneumonia with severe alveolar and interstitial oedema and interlobular emphysema. The lungs are enlarged, pale, rubbery, with lesions most notable in the caudal lobes. Microscopically, eosinophils and larvae are seen in exudate. The lesions are alveolar and interstitial oedema and emphasema, formation of hyaline membranes within alveoli and in those animals that survive for several days, hyperplasia of type II alveolar epithelial cells.

Answer 1226

life cycles: similar to cattle. Direct life cycle, and the females are ovo-viviparous (the females lays eggs which contain mature larvae). clinical signs: usually non. Coughing and weigh loss in heavy infestations due to obstruction of the bronchi by adult worms, but very uncommon. Weight loss. May be severe when immune system compromised eg concurrent Johnes disease diagnosis: Baermann test, Post mortem Gross pathology : areas of atelectasis and pneumonia. Microscopically characterized by a catarrhal, eosinophilic bronchitis with peribronchial lymphoid hyperplasia of type II pneumocytes and focal infiltration of lymphocytes and an alveolar exudate. Secondary bacterial pneumonia is common.

Answer 1227

Life cycle: requires slugs or snails as intermediate hosts parasite infects a snail or slug intermediate host. snail or slug is subsequently ingested by a sheep or goat while grazing. larvae migrate to the lungs by the lymphatic system and cross into the alveoli or bronchioles.[1][5] In the alveoli, the larvae mature to the adult stage, and the adults lay their eggs in the lung tissue. The eggs rapidly hatch, and the larvae are coughed up or swallowed.[5] The larvae are expelled into the environment in the sputum or feces.[5] The larvae reinfect a snail or slug to complete the life cycle. Clinical signs: usually non Diagnosis: Baermann test, Post mortem Gross pathololgy: multifocal, subpleural nodules, found mostly in the dorsal areas of the caudal lobes. The nodules are soft and haemorrhagic in the early stages, but later become grey-green and hard or calcified. Microscopically, a focal eosinophilic and granulomatous reaction occurs in the subpleural alveoli where the adults, eggs and larvae reside.

Answer 1228

Metastrongylus apri, Metastrongylus edentates Life cycles: requires an earth worm as an intermediate host. Therefore parasite only occurs where pigs have access to earth in an outside environment. Worms found in the lungs 20-24days after the pig consumes the thick walled egg (contains L1 larvae). Clinical signs: coughing and dyspnoea in young/growing pigs. (adults appear immune) Diagnosis: clinical signs, history, management. FWEC-thick walled eggs containing larvae Gross pathology PM- adult worms are 45mm long, found in/squeezed out of bronchi or bronchioles of the diaphragmatic loves of the lungs. Pulmonary emphysema may be seen in caudal parts of the diaphragmatic lung lobes.

Answer 1229

Sheep respiratory retroviruse Highly transmissible, retroviral induced neoplasia of the lungs. Clinically characterized by a long incubation period. Spread by aerosolized respiratory droplets, and from ewe to lamb via milk or colostrum. Young lambs are most susceptible to JSRV infection and the time between infection and clinical signs developing (incubation time) is dependent on the age of sheep at infection and the dose of JSRV. Found around the world, in particular in Scotland where there have been efforts to control its spread. 60 and 85 cases are diagnosed in veterinary labs in Scotland, England, and Wales per year, but this is certainly an underestimate It is a neoplasm that presents as a pneumonia Mainly affects mature sheep Not naturally transmissible to goats Affects mainly mature sheep, sometimes coughing and distress (particularly after exercise), lag behind the flock Gradual loss of condition 10 to 40 ml per day of frothy, clear or at times pinkish fluid/mucus is common to pour from the nostrils but this can be up to 400 ml per day. Around one third of cases don’t produce any fluid. Normal appetite, normothermic Death (after several months). Sometimes noticed as an increase in ‘sudden’ deaths Cases peak in January and February due to affected sheep being unable to cope with adverse weather conditions and nutritional restrictions at that time of year. Raise the pelvic limbs ‘wheelbarrow test’: copious, thin mucoid fluid, pours from the nostrils (not welfare friendly! Like drowning!) Ultrasound examination of the lungs detects early disease (cull). only detect tumours over 1 cm in size in the ventral areas of the lungs. Therefore, it is not possible to guarantee absence of OPA in individual animals. any sheep with suspicious lesions at scanning are quarantined and scanned again 2 months later. Post mortem (gold standard) Histopathology No commercial lab test for live animals-A PCR test has been used in research studies, but it lacks the sensitivity for field diagnosis in individual animals Early: Lungs are enlarged, heavy, wet and fail to collapse. Contain several firm, grey, well demarcated variably sized nodules. Later stages: nodules become confluent and large segments of both lungs are diffusely but not symmetrically, infiltrated by neoplastic cells. On cross section, a copious mucoid secretion is in the airways Sequalae includes: secondary bronchopneumonia, abscesses, fibrinous pleural adhesions, and metastasis occur to tracheobronchial and mediastinal lymph nodes, and to a lesser extent to the pleura, muscle, liver and kidneys.

Answer 1230

Sheep respiratory retroviruse Important, highly infectious, slow viral (lentivirus) disease in sheep Maedi means ‘shortness of breath’ and Visna means ‘wasting or shrinking of the nervous system’ in Icelandic It is sometimes referred to as lymphoid interstitial pneumonia Caused by a non oncogenic retrovirus of the lentivirus subfamily Seroepidemiological studies indicate that infection is widespread in the sheep population, yet clinical disease is rare. The pathogenesis is not completely known. The transmission is thought to occur through ingestion of infected colostrum and milk, close contact and inhalation via droplets from the nose and mouth, cross contamination of blood from punches and needles The virus remains for long periods of time in monocytes and macrophages. Clinical signs do not develop until an incubation period of over 2 years Experimentally the incubation period can be reduced if lambs are inoculated intratracheally with ovine lentivirus in the perinatal period Goats are considered to be susceptible: the same virus causes Caprine Arthritis Encephalitis (CAE) in goats and can be passed between the two species. Impact on the flock MV has a long incubation period and the disease can spread unnoticed for many years before the signs are seen. By this time it is likely that at least half of the flock is infected resulting in high levels of culling. The potential economic impacts are: * 10-20% adult mortality after the development of clinical signs * Lamb mortality and reduced growth rates due to lack of colostrum/milk * A reduction in conception rates * Increase in culling rate An MV prevalence survey in 2013 found that in the 15 year period since the previous survey: * The number of flocks with MV doubled (from 1.4% to 2.8%) * The number of infected sheep increased almost four fold (2 per 1,000 to 8 per 1,000) * Within affected flocks the average proportion of infected sheep almost doubled (13% to 24%) Dyspnoea Insidious slowly progressive emaciation despite good eating Chronic mastitis Progressive weakness leading to paralysis Arthritis Death (may take months) Serological testing (screening packages and accredited free status available) Post mortem Severe interstitial pneumonia, lungs fail to collapse when thorax opened. Rib imprints on the lung surface Lungs are pale, mottled and heavy (2-3 x normal). Regional lymph nodes enlarged. Other pathology: encephalitis, non suppurative arthritis with periarticular fibrosis, lymphofollicular mastitis, or vasculitis Combination of these lesions or remain infected but disease free for life

Answer 1231

Pyrexia Fever Respiritory distress Petechial haemorage Sudden death Vomiting Cutaneous erythema Enlarged friable spleen Haemorages in lymphnodes- Gastohepatic lympnode specifically Haemorage in kidneys Oedema of gall blader Perirenal oedema

Answer 1232

immunohistocheistry- Good for determining tumour type Electron microscopy could be helpful but is not appropriate outside of a research project

Answer 1233

Struvite is more likely in bacterial infections The bacteria have been phagocytosed so it is usually they are a result of contamination and it is a true bacterial infection Bacterial urine culture is next best step

Answer 1234

Serum total thyroxine (T) 4 levels it is a clinical sign of hyperthyridism serum iodine is more a concern in farm animals

Answer 1235

Hyperadrenocotisism Hyperthyroidism Diabetes melatus would be a ifferentail for pupd but coat condition is not caused by this

Answer 1236

Intranuclear inclusion bodies

Answer 1237

SMEDI- stillbirth, mumification, embryoinic death, infertility Porcine parvo virus

Answer 1238

Zheil neilson

Answer 1239

Urea and createnine ok and so kidneys ok Liver markers are ok so liver ok Intestinal biopsy would be most useful- inflammatory bowl disease, lymphoma

Answer 1240

liver Hepaticecepalopathy- build up of amonia

Answer 1241

Fructosamine test

Answer 1242

Suprative arthritis Culture

Answer 1243

Facial nerve paralysis mydriasis could be due to guteral pouch disease or neck injury

Answer 1244

Salmonella- all birds Chlamydia psittiaci- in chicken turkeys and parrots Avian mycoplasmosis Mycoplasma gallisepticum & Mycoplasma meleagridids- in chicken and turkey

Answer 1245

whiote discolouration in caeca- ceacal cores would be cultured and reported if pathegen found game birds often carry salmonella and so bacteriology must always be done in liver

Answer 1246

presents with swolen head sparce fetheratin around eye- swelling increases distance in feahers, closed eye exudate in nasal cavity

Answer 1247

Avian influenza newcastle disease west Nile Virus- not currently in uk but birds are being screened

Answer 1248

1. Mortality- most important 2. Neurological signs 3. Intestinal signs

Answer 1249

Pancreatic necrosis splenic necrosis Pulmonary congestion and pneumonia Hydropericardium but sometimes there is nothing to see- very acute disease

Answer 1250

wet smears done at post mortem in recently euthanised animal from mid-intestine and caeca

Answer 1251

an opening between the nasal and oral cavity in birds good place for swab sampling for PCR

Answer 1252

5-75% mortality in chickens 100% in turkeys As low as 0% in ducks Incubation of 3 to 10 days Winter virus Current strain is H5N1 (hemagglutinin type 5 and neuraminidase type 1) influenza virus Waterfowl/shorebirds, poultry, mammals Anseriformes/Charadriiformes (natural reservoir hosts)- Asymptomatic carrier species (i.e. mallards) Sentinel species (i.e. swans) Non waterfowl species (i.e. ostriches, falcons) High mortality in farmed poultry (chickens and turkeys) Variable morbidity and mortality in wild birds Influenza A virus - Orthomyxoviridae - RNA virus Subtypes: antigenic variation in haemagglutinin (HA, 16 subtypes) and neuraminidase (NA, 9 subtypes) glycoproteins Low pathogenic and highly pathogenic strains Based on experimental poultry infections LPAI - typically wild birds HPAI - poultry with spill over to wild birds LPAI - prevalence peaks in late summer and early winter Species and location dependent HPAI - often associated with autumn migration Acute infection (~4-8 days) ends with an immune response or death Variable clinical signs LPAI - subclinical HPAI - lethargy, respiratory and neurological signs Macroscopic Findings: Emaciation and muscle wastage (juveniles) PANCREATIC HAEMORRHAGE AND NECROSIS Duodenal, myocardial and air sac haemorrhages Pulmonary congestion, oedema and consolidation Hepatosplenomegaly Histopathological Findings: Necrotising pancreatitis and hepatitis Lymphoplasmacytic encephalitis with neuronal necrosis and neuronophagia Confirmation of infection- Virus isolation (PCR) Demonstrating viral nucleic acid or antigen in tissues (IHC) (Fig 3D)

Answer 1253

Paramyxovirus Affects- respiratory system (mainly respiratory disease) Intestinal system Neurological system Labored breathing Head shaking “snicking”- birds cannot cough or sneeze due to no diaphragm so headshake to expel air fro respiratory tract Lesions in gizzard- hemorrhagic lesions in gastric glands (not pathognomonic) Green scour Torticollis- twisting of neck, stargazing ect Ataxia Can vaccinate against it and routinely do- live and attenuated vaccines Vaccines administered to chicks on raring farm- primed with live and boosted with dead vaccines

Answer 1254

Cotton like lesion in airsacks Labored breathing Abdominal breathing Typically in game birds Typically don’t die but do show signs Comes in on wet bedding and straw so is seen in birds housed on straw

Answer 1255

Syngamus trachea Seen often in game birds- disease of stocking density Found in trachea- male and female attached toghther and consume blood form the trachel wall which they are attached to Bird cough up eggs they are producing and swallow them Birds will “gape” Lifecycle 3 weeks Use anthelminthic- worm every 3 weeks- meat withdrawal 8 days at longest. Not given medicine at point of release with game birds Without treatment the worms will eventually block windpipe

Answer 1256

Fungal infection of crop Older birds crops sag and food sits at the bottom of crop and ferments

Answer 1257

Tvp- transmissible viral proventriculitis- effects ability of gastric glands and lining of gizzard Mechanical damage of gizzard- nails, wires, large grit, failure pf coilus (protective barrier)

Answer 1258

Exact landmark between jejunum and illium Reminanat of yolk sack- residual scar tissue

Answer 1259

inflammation and/or infection of the umbilical vein

Answer 1260

inflammation of the caeca often protozoal disease typhlitis

Answer 1261

Motile protzoal disease Not same presentation in different birds- different species, species specific, no cross infection Chickens- affected by several species in the Eimeria family: In duodenal loop you can see white scars with Eimeria. Acervuline (a comes first)- Lifecycle- 7-8 days: after 3 cycles chicken often cannot cope Red dots all along the intestinal tract are indicative of Eimeria. Maxima- the oocyst is largest microscopically (effects large amount of tract)- chicken most effected after 4 lifecycles, day 21 Heamorage of the caeca is a typical presentation of Eimeria. Tenella Alphabetical order of portion of tract they effect: AMT Eimeria. Brunetti (b for bum) effects colon Eimeria. Necatrix- seen in all of digestive tract, though not often not caeca Biggest economical cost to broiler industry Biggest economical cost to broiler industry All linked to necrotic enteritis

Answer 1262

('MD' or 'fowl paralysis') is a very common disease of chickens caused by a herpes virus Infected for life Virus becomes dormant in nervous tissue Clinical singns- nervous Legs splayed out- completely ataxic Torticollis Transient paralysis Often infects younger bird- fliars up at point of stress like lay Commercial long living birds (breeders and layers) routinely vaccinated but broilers are not- inactivated virus No treatment Sample sites are sciatic nerve- infected nerve much larger Feather follicle- virus sheds in dander and so can be found Can live in environment for 20 years or more

Answer 1263

Formerly Atoxoplasma Protozoan parasite- Obligate intracellular coccidian Enteric form- present Throughout birds Intestinal form Oocysts shed in faeces Diarrhoea and weight loss Systemic Isosporiasis- Restricted to the order Passeriformes Extraintestinal/visceral form Clinical significance and pathogenicity questionable Often subclinical Morbidity and mortality uncommon Restricted to fledglings exposed to high parasite loads or stress-induced reduction in immunity associated with overcrowding / co-morbidities Gold standard: direct visualisation of asexual merozoites within circulating mononuclear cells Buffy coat or impression smears Difficult ante-mortem Blood sampling challenging, visceral impressions PM qPCR for pooled faecal samples Post Mortem Examination less sensitive Macroscopic findings Often unremarkable Splenomegaly and hepatomegaly Histology used to assess host response instead of detection Lymphocytic, lymphohistiocytic or lymphoproliferative splenitis and hepatitis Widespread dissemination in severe cases Neoplastic transformation rarely reported can see Intracytoplasmic merozoites within a parasitophorous vacuole that peripheralise and indent the nucleus

Answer 1264

Trichomonas gallinae Flagellated protozoan parasite- Most species are commensals of the GIT Pigeons (canker) - primary carriers Birds of prey (frounce) - feeding on infected birds Gardens birds (finches in particular) - UK epidemic in 2006-2007 Transmission via contaminated food or water Clinical signs: lethargy, fluffed up plumage, dysphagia, dyspnoea Predispose to aspiration pneumonia Concurrent fungal (Candida) or bacterial (S. aureus) infections are common Diagnosis- Identification of motile flagellates on a wet mount Culture or PCR from swabs/tissues Organisms are round to ovoid, ~ 5–7 µm in diameter with a small condensed nucleus Macroscopic findings Yellow mucosal plaques - oropharynx, oesophagus, crop Lesions extend into the subjacent soft tissues, bone and nasal cavity Histology findings- Fibrinoheterophilic and necrotising (diphtheritic) inflammation Stomatitis, oesophagitis, ingluvitis +/- flagellates at the leading edge

Answer 1265

Salmonella enterica serovar Typhimurium Songbird salmonellosis – passerines- Seed eating birds: greenfinches, house sparrows Can also affect waterfowl and shorebirds Outbreaks more common in cold months or during migration Can be associated with crowding at feeders - faecal oral transmission Clinical signs: Found dead Non-specific signs: lethargy, fluffed plumage, weight loss Pasting of faeces at the vent Diagnosis: Bacterial culture - crop/oesophagus or in multiple organs in disseminated cases (septicaemia) Macroscopic findings Acute: pinpoint white lesions in the liver and spleen Chronic: multifocal caseous nodules / necrotising ingluvitis and oesophagitis Histology findings- Foci of necrosis - crop, oesophagus or multiorgan necrosis (liver, spleen etc.) Infiltrating heterophils and macrophages (Fig 7) with intra- and extracellular gram-negative bacilli (arrows) Incidence and prevalence are currently low compared to 2000s Prevention and control - hygiene (can persist in the environment) Zoonotic risk (very low compared to other causes of salmonellosis in humans)

Answer 1266

Poxviruses - Avipoxviruses - large, enveloped DNA virus Affects a wide variety of bird species globally (different strains)- UK - great tits most frequently affected Transmission via direct contact, fomites or biting insects (mosquitos) Cutaneous or diphtheric forms - Cutaneous more common in passerines Macroscopic findings Wart-like growths on non-feathered skin (feet, digits, cere, periorbital) Histologic findings- Epithelial hyperplasia (epidermis and follicles) Swollen epithelial cells with cytoplasmic vacuoles/oedema (ballooning degeneration) Few to numerous variably sized (often large) eosinophilic, intracytoplasmic inclusion bodies (Bollinger bodies) Lesions can be self-limiting and regress spontaneously over weeks Can affect vision, feeding and perching- Trauma, emaciation Opportunistic bacterial and fungal infections- Contribute to morbidity and mortality

Answer 1267

Papillomaviridae - Papillomatosis - tassel foot Fringilla coelebs papillomavirus (FcPV1) Epitheliotropic double-stranded DNA virus - host specific Cnemidocoptes - Cnemidocoptosis - mange / scaley leg C. jamaicensis and C. intermedius - affect 10 species of European finches Burrowing mite Chaffinches most common; rarely brambling, bullfinch and greenfinch Transmission via contact Mixed infections are common Minimal clinical significance - low mortality Macroscopic findings - Proliferative leg lesions (FcPV1 & Cnemidocoptosis) Unilateral or bilateral (Squamous) papillomas and wart-like growths Nodular or hyperplastic lesions with deeply fissured papillary growths (i.e. papilliferous) Grey/white diffuse scale, “powdery” to severe hyperkeratosis with crusts and scabs Histologic findings - Proliferative leg lesions (FcPV1 & Cnemidocoptosis) Epidermal hyperplasia, papillary projections, hyperkeratosis, keratinocyte vacuolation, acanthosis FcPV1 - Intranuclear inclusion bodies Cnemidocoptosis - Sections through mites Diagnostic Tests - Proliferative leg lesions (FcPV1 & Cnemidocoptosis) Histology FcPV1 - PCR Cnemidocoptosis - NaOH digest of skin lesions

Answer 1268

Common in all wildlife species Accidental (i.e. window strike) Secondary to a primary disease process (i.e. falling from a perch due to poxvirus/FcPV2/Cnemidocoptosis lesions) Iatrogenic (i.e. traps, firearms, fencing) Predation (i.e. domestic cats) Haemorrhage - subcutaneous, coelomic Fractures - appendicular skeleton, cranium, beak Anaemia and Neurological deficits Limb amputation- Traps Accidental collisions with fences

Answer 1269

Key points The domestic cat is the main host although other felids can be infected Prevalence high; large populations, shelters Acute upper respiratory and ocular disease, particularly severe in young kittens Almost all cats undergo a latent infection, which can lead to recurrent clinical signs, mainly ocular diseases (conjunctivitis and keratitis) after intermittent reactivation The virus enters the body via the nasal, oral or conjunctival routes. Acute disease usually resolves within 10 to 14 days although ocular signs, in cases of keratitis, can persist longer. Some animals develop chronic lesions in the upper respiratory tract and in ocular tissues. Following infection, the virus spreads along the sensory nerves and reaches the neurons, particularly in the trigeminal ganglia. It is thought that all cats experiencing primary infection are likely to become lifelong latent carriers. CLASSICAL ACUTE- Rhinitis, conjunctivitis, tracheitis Corneal ulcers* Sneezing, nasal discharge, salivation, coughing, conjunctival hyperaemia and serous ocular discharge ATYPICAL ACUTE- Peri-ocular and facial dermatitis Viraemia, pneumonia Nasal and facial ulcerated and crust-forming lesions Severe systemic signs, coughing, death (acute death in kittens, “fading kitten syndrome”) CHRONIC - Stromal keratitis Chronic rhinosinusitis* Corneal oedema, vascularisation, blindness Chronic sneezing and nasal discharge

Answer 1270

Key points Highly contagious, widespread distribution No known reservoirs or alternative hosts A single diverse genogroup Infected via the nasal, oral or conjunctival routes Prevalence is broadly proportional to the number of cats in a household High FCV prevalence within a colony is associated with high FCV strain diversity Cats can be infected with FCV via the nasal, oral or conjunctival routes. Acute oral and URT disease – ulcerative lesions on tongue Acute mild respiratory disease Pneumonia – young kittens Feline chronic gingivostomatitis?? Limping syndrome FCV less commonly affects other tissues, such as the lungs, leading to pneumonia Co-infections of feline herpesvirus (FHV) and FCV are generally very common and have been described in kittens with pneumonia; FHV infection leads to airway damage, which might facilitate secondary infection with FCV due to reduced mucociliary clearance and impaired immune defences Acute synovitis with thickening of synovial membranes and increased synovial fluid have been noted in cats with limping kitten syndrome Limping kitten syndrome can also occur after FCV vaccination with some modified live virus vaccines.

Answer 1271

VS-FCV strains cause: widespread vasculitis multi-organ involvement very high mortality CASE: Severe respiratory disease in a large colony of farm cats High morbidity and mortality, no URT Tachypnoea progressing to dyspnoea Different cell tropism-

Answer 1272

Feline allergic miliary dermatitis Feline mosquito bite sensitivity Feline herpesviral ulcerative dermatitis Feline cowpox viral infection Feline indolent ulcer (Eosinophilic Granuloma Complex) Feline idiopathic ulcerative dermatosis (underlying abscess, neoplasia, trauma etc)

Answer 1273

Key points Orthopoxvirus usually cowpox virus Wide host spectrum including man zoonosis! Rodent contact Skin lesions predominantly on the head and paws Usually heal spontaneously, in severe cases progressive proliferative ulcerations ensue In kittens and immunosuppressed cats, generalized cowpox infections frequently take a fatal course Corticosteroids enhance systemic spread of the virus and are contraindicated enters via bitewound from rodent Potential ZOONOSIS If immunosuppressed (FeLV/FIV) or treated with steroids: necrotising pneumonia, nasal discharge, diarrhoea, death – don’t give them steroids!!! Oval to circular ulcerated papules and plaques with crusting Diagnostic tests – on the scab PCR*** Serology for Ab titre

Answer 1274

Trauma Neoplasia (SCC**, sarcoma) Eosinophilic granuloma complex lesion Ulcerative glossitis as part of a more generalised stomatitis, a common condition especially of older cats; multifactorial: imbalance in oral microbial flora feline calicivirus feline herpesvirus 1 possibly an immune-mediated component? A more generalised underlying condition, for example uraemia Papillomavirus lesions – plaques, feline “sarcoid” – fibropapilloma

Answer 1275

1. Basal cell tumours 22.6% 2. Fibrosarcoma 19.5% 3. Squamous cell carcinoma 11.4% 4. Mast cell tumour 6.8%

Answer 1276

Actually a group of tumours, all composed of basal cells Can be grossly cystic and/or pigmented (ddx melanoma) The two most common types in cats include: Apocrine ductal adenoma Trichoblastoma (hair follicle origin) Not always sub-classified BENIGN

Answer 1277

Second most common Including FISS** Most (but not all) considered low to intermediate malignancy Infiltrative and often locally recurrent Metastasis is uncommon Grading system proposed Surgical excision = treatment of choice

Answer 1278

Often but not always fibrosarcoma More aggressive, larger, younger cats Highly recurrent Metastatic potential Anatomical location Infiltrative behaviour Pleomorphism Lymphocytic infiltrates Macrophages with intracytoplasmic pigment (adjuvant) A compatible history

Answer 1279

Approx. 1% Cutaneous/subcut nodules Abscesses which do not heal or are only partially responsive to AB S.W., S.E. of London, N. England or S. Scotland Potential zoonosis Histopath = first line of diagnosis If you suspect Mycobacteriosis, say so on the form so the pathologist can request a ZN stain Diagnostic if acid-fast organisms are seen But not necessarily excluded if negative Histopath cannot speciate Culture of fresh or frozen tissue (50%, can be very slow) IFNg release assay (blood test) 70-100% sensitive PCR based; fresh preferred, can use formalin-fixed Other presentations: GIT – mass lesion – outbreak associated with raw feeding Ocular lesions

Answer 1280

More common feline fungal rhinitis Can also present as cutaneous lesions Opportunistic pathogen Coexistent debilitating disease / immunosuppressive diseases Potentially zoonotic Saprophyte organism Soil contaminated with pigeon excrement Most common systemic fungal infection of cats Multiple organs may be involved; respiratory tract disease, subcutaneous nodules, lymphadenopathy, intraocular inflammation, fever, or central nervous system (CNS) diseases always advise identification either by culture or PCR testing, prior to deciding on treatments Cerebral cryptococcosis with so-called “Soap bubble” lesions (pathognomonic)

Answer 1281

Dermatophytosis aka “Ringworm” Culture advised Systemic therapy is the treatment of choice Can be difficult to eradicate Asymptomatic carriers Potential zoonosis, especially in immuno-compromised individuals Microsporidium canin (natural host is cat not dog), Trichophyton mentagrophytes and M. gypseum are the most common isolates. Culture is advised in these cases to determine which species is involved since this may affect client advice and treatment regime. In general terms, systemic therapy is the treatment of choice, but this can be a difficult condition to eradicate successfully, especially in multi-cat households, where asymptomatic carriers may perpetuate the condition. Be aware that this is a potential zoonosis, especially in immuno-compromised individuals.

Answer 1282

Abdominal – Thoracic – Bicavitary - Pericardial FIP (“wet form”) Cardiac causes Liver disease Hypoproteinaemia Purulent - peritonitis Neoplastic – abdominal tumours - mesothelioma Haemorrhage – amyloidosis liver Urine – ruptured bladder

Answer 1283

Key points Feline coronavirus (FCoV) is ubiquitous Most FCoV-infected cats either stay healthy or show only mild enteritis Only a small proportion of FCoV-infected cats goes on to develop feline infectious peritonitis (FIP) FCoV transmission is faecal-oral via litter trays and fomites FCoV infection of monocytes is the key event in FIP pathogenesis Internal mutation theory = internal mutations of FCoV = switch of cell tropism arising in an individual cat = development of highly pathogenic FIP-inducing FCoV Pedigree cats, under two years old Sample the effusion GOLD STANDARD diagnosis of FIP = histopathological changes + FCoV antigen IHC Positive FCoV antibody is not confirmatory of FIP Absence of FCoV antibodies makes FIP less likely. Coronaviral genomes possess a high level of genetic variation due to the error rate of RNA polymerase leading to different types of mutations. FCoV infection occurs following ingestion of the virus (e.g. by grooming paws contaminated with faeces during litter tray use) FCoV then replicates in the epithelial cells of the small intestinal villi, resulting in faecal shedding within a week enteric FCoV infection is often asymptomatic but can result in enteritis FCoV is then found in the colon where the main site of viral replication is the ileo-caecocolic junction. FCoV infection can then spread to the mesenteric lymph nodes followed by viraemia in the blood. low level FCoV viraemia in monocytes can occur in cats that do not go on to develop FIP Immune response can clear the infection at these stages still, even with low level viraemia efficient and high FCoV replication in activated monocytes and macrophages (which are likely mediated by viral mutations) is believed to be a key event in FIP pathogenesis, alongside the nature of the immune response mounted by the cat in response to FCoV infection. When FIP develops there is a reaction between replicating FCoV in monocytes and blood vessel walls, allowing extravasation of the monocytes, where they differentiate into macrophages. Breakdown of the endothelial tight junctions Virus survives and replicates in large numbers = HIGH VIRAL LOAD Virus replicates within monocytes and macrophages Activated = VASCULITIS** and PERIVASCULITIS Breakdown of endothelial tight = junctions plasma leaks out Effusion in the abdominal, thoracic and/or pericardial cavities WET FORM Often fast developing Larger perivascular pyogranulomata More chronic – DRY FORM Mass lesions Signs depend on vessel location: Liver Lungs Kidneys Brain Intestines EYES** Liver with fibrin deposition over the capsular surface cerebrum, with dilated lateral ventricles (hydrocephalus) Granulomatous inflammation obstructing CSF outflow at level of mesencephalic aqueduct “Dry” FIP often has ocular changes, such as uveitis, hypopyon, vasculitis History suggestive? lymphopaenia non-regenerative anaemia increased TP, hypergammaglobulinaemia, low alb/glob ratio high a1 acid glycoprotein and high FCoV titres Effusions: positive Rivalta’s test high protein low alb/glob ratio neutrophils and macrophages typically straw coloured, clear and non-odourous Biopsy – typical lesions and positive staining cells by immunofluorescence/IHC currently gold standard RT-PCR

Answer 1284

As a cause of sudden unexplained death? Initial differential list: Cardiac disease asymptomatic cardiomyopathy (HCM, ARVC) less likely valvular disease (endocarditis) pericardial disease neoplasia (lymphoma, heart base mass) congenital heart defect Trauma Pre-existing disease (non-cardiac) Toxin exposure (malicious or accidental)

Answer 1285

Cardiomyopathy HCM (LVOTO, ES-HCM); 1° vs 2° DCM (taurine) ARVC UCM Hypertrophic cardiomyopathy (HCM) most common form 15% of the domestic cat population, primarily as subclinical disease severe HCM leading to heart failure or arterial thromboembolism (ATE) only occurs in a small proportion of these cats a genetic cause of HCM has been identified in two breeds and is suspected in another, but for most cats the cause is unknown.

Answer 1286

Gastrointestinal; Neoplastic (lymphoma, mast cell tumour, carcinoma, sarcoma/GIST) FIP Fungal granuloma Feline Gastrointestinal Eosinophilic Sclerosing Fibroplasia Mycobacteria Other sites; splenic, hepatic, lymph nodes, pancreas, bladder, kidneys, adrenal glands

Answer 1287

most commonly diagnosed neoplasm in cats presents in various forms and clinical signs, depending on the organs / site(s) affected There are various ways of classifying lymphoma in cats: Phenotype Anatomical site Viral versus non-viral related Anatomical site lack of consensus between studies primary lymphomas with nodal involvement Broadly classified into four anatomical groups: Multicentric Mediastinal/thymic (confined to the thoracic cavity) Alimentary (sometimes includes renal and hepatic) “Extra-nodal” Anatomical site: extra-nodal, non-GI lymphomas NASAL/Upper Respiratory Tract pharynx, larynx and trachea as well? vast majority of nasal lymphomas = B-cell origin appears to carry the best prognosis OCULAR uncommon site unilateral or bilateral often present in multicentric forms may affect the uvea, the cornea, rarely the retina may also involve the retrobulbar space = exophthalmos RENAL older cats (not always) often if not always bilateral often presents with involvement of other organs (but not always) majority = B-cell origin CNS Traditionally the most common spinal tumour in cats; FeLV? can also be present as an intracranial mass often involvement of other organs; spinal and renal lymphoma lowest response rate Feline gastrointestinal lymphoma Mucosal only – T-cell Most common form Diffuse Difficult to distinguish from diffuse lymphocytic enteritis MST = 29 months Low grade Transmural – T-cell or B-cell B-cell transmural lymphomas stomach, jejunum, ileo-caecal-colic junction Presents as a mass MST = 1.5 months for T-cell MST = 3.5 months for B-cell Intermediate or high grade Viral verses non-viral related, i.e. whether or not the tumour is associated with infection with FeLV and/or less commonly FIV. Viral related: Younger cats Certain anatomical sites multicentric mediastinal/thymic possibly the CNS. As vaccination against FeLV has become more widespread, the relative numbers of these types of lymphoma have declined, changing the pattern of disease we see clinically and diagnostically.

Answer 1288

Retrovirus, prevalence in Europe generally low – vaccination Infection normally via saliva (grooming, shared bowls, bites) Does not survive long outside the host Viral RNA → → reverse transcription → → viral DNA → → usually incorporated into host genome ( = provirus) Diagnostic tests FeLV p27 antigen (in house) – detects Ag in circulation FeLV provirus – detects genome integrated FeLV proviral DNA FeLV RNA – detects RNA in circulation **BEWARD FALSE POSITIVES** in FeLV p27 antigen test in areas of low prevalence ABORTIVE INFECTION- Circulating anti-FeLV antibodies Infection not detectable (negative on p27 Ag and PCR) REGRESSIVE INFECTION Proviral DNA remains in DNA of host cells (DNA PCR positive) Cat has overcome viraemia / no viraemia (p27 Ag negative) Viraemia can be reactivated PROGRESSIVE INFECTION Viraemia persists Shedding FeLV Often develop FeLV associated diseases (positive on p27 Ag and DNA PCR) Clinical signs in persistently FeLV viraemic cats Anaemia (mostly non-regenerative) Immune suppression Lymphoma (mediastinal, peripheral, spinal) Less common: Other lymphoma, other neoplasia, immune-mediated uveitis, reproductive, peripheral neuropathies

Answer 1289

Retrovirus, closely related to HIV Endemic; seroprevalence varies between regions Most infections acquired by bites (fights, mating) from persistently infected cats Long asymptomatic phase (years, some never develop disease Clinical signs – immunodeficiency causes…. Chronic gingivostomatitis Lymphadenopathy Chronic rhinitis Weight loss Renal failure (immune mediated glomerulonephritis) (neoplasia, incl lymphoma/leukaemia, bone marrow disease, neurological signs)

Answer 1290

Middle aged cats Ragdolls Long histories! Palpable mass, hard Pylorus and ICC often Lymph node involvement Cause????

Answer 1291

Hyperthyroidism – functional hyperplasia / adenoma Progresses over time to well-differentiated carcinoma? Often bilateral Beware hypocalcaemia in bilateral thyroidectomies Beware ectopic thyroid tissue!

Answer 1292

Lung-digit syndrome Fungal / bacterial infection PF Giant cell granuloma

Answer 1293

Primary lung neoplasia metastases to digits It’s a cat thing!

Answer 1294

Lump on cat toe close to nail bed Multinucliated giant cells Mitotically active spindle cell populations Not really turmours- reactive change in nail bed Not malignant Can also see in mouth

Answer 1295

SNAP test Loss of crypts in intestinal histology Knocks out eplicating crypt epithelial cells- can no longer produce intestinal epithelium Remianing epithelial cells become flattened and elongated or hyperplastic to compensate High mortality rate particularly in kittens Enteritis dhiarea High mortality (more than 90% in kittens) Diagnostic tests Faecal testing for FPV antigen (PCR on whole blood, faeces) IHC available Basophilic IN inclusions in enterocytes, lymphocytes (early) Diseases it causes include (targets replicating cells) Diarrhoea, enteritis Lymphopaenia, neutropaenia, thrombocytopaenia and anaemia Cerebellar ataxia (kittens) Abortion

Answer 1296

Liver: hepatic necrosis Lung: interstitial pneumonia Heart: necrotizing myocarditis IHC confirmed Toxoplasmosis gondii Systemic Toxoplasmosis- Cats = definitive host of Toxoplasma gondii Organism can infect a wide variety of species (birds, rodents, herbivores, carnivores) which may act as intermediate hosts. Infection widespread in most domestic animals (and humans) Overt disease is rare except as a cause of abortion in sheep and goats (and, rarely, transplacental infection in humans) Systemic toxoplasmosis occurs most commonly in young or immunocompromised animals and corticosteroids, 'stress' or infection with immunosuppressive viruses (e.g. FeLV/FIV in cats) may exacerbate disease or reactivate a latent infection. IMPORTANT NOTE: THIS INFECTION HAS ZOONOTIC POTENTIAL

Answer 1297

Serious disease, essentially 100% fatal Morbillivirus (causes canine distemper) accelerated syndrome in ferrets Disease progression: 12 days in ferret-adapted strains 42 days in wild canine strains Profoundly immunosuppressive animals that survive this stage succumb to neurologic dysfunction within several weeks Gross lesions similar to those seen in the dog: Photophobia Oculo-nasal discharge Hyperkeratosis of the planum nasale and footpads Papular rash Bronchopneumonia Non-suppurative encephalitis with demyelination = neurologic disease

Answer 1298

2006 – novel granulomatous disease in ferrets resembling the dry form of FIP Ferret coronavirus known to cause epizootic catarrhal enteritis Gross lesions resemble dry form of FIP (systemic form) Granulomas - mesentery, abdominal and less commonly thoracic organs Affected animals may show: mild anaemia, thrombocytopaenia, hypergammaglobulinaemia Epizootic catarrhal enteritis = coronaviral disease of ferrets, epizootics of high morbidity (up to 100%), but low mortality Ferret enteric coronavirus (FECV) diarrhoea - rapidly dehydrating and most mortalities occur in older animals with concurrent illness vomiting dark green stool with abundant mucus

Answer 1299

only domestic animal species susceptible to human influenza viruses often infected by their human owners clinical signs: photophobia catarrhal nasal discharge sneezing, coughing, pyrexia anorexia, and malaise

Answer 1300

ferrets caused by a parvovirus In mink: rapidly life-threatening immune-mediated glomerulonephritis, vasculitis and hypergammaglobulinaemia In ferrets: notable similarities, including hypergammaglobulinaemia, immune complex glomerulonephritis (later stages) In ferrets, the disease is much more insidious, with progression as long as 2 years Ferrets in the late stages of disease will be hyperproteinaemic

Answer 1301

Adrena and pancreatic most common- endocrine disease Cutaneous and subcut lymphoid

Answer 1302

Common, middle aged to older ferrets proliferative lesions adrenal cortex = excess amounts of oestrogenic hormones (hyperplasia, adenoma, or carcinoma) Cutaneous, behavioural, and reproductive signs (not to be confused with Cushing's disease) Bilaterally symmetrical alopecia Enlarged vulva in a spayed female

Answer 1303

Common neoplasm Hypoglycaemia due to inappropriate secretion of insulin Clinical signs include: lethargy, stupor, ptyalism, and ataxia Progressing to coma and death Potentially malignant, metastasis is rare (cf dog and cat)

Answer 1304

Sebaceous epitheliomas Mast cell tumours Dermal leiomyomas, leiomyosarcomas (piloleiomyomas) Vaccination-site fibrosarcomas

Answer 1305

COMMON Most are spontaneous, is there a retroviral infection? 1). older ferrets, primarily peripheral lymphadenopathy, visceral spread and subsequent organ failure late in the course of disease 2). young ferrets less than two years of age. Early visceral neoplasms, often with a large thymic mass 3). uncommon form, in which combinations of peripheral lymphadenopathy and visceral neoplasms and numerous bizarre lymphoblasts may be seen, known as the immunoblastic polymorphous variant.

Answer 1306

Most common neoplasm of the musculoskeletal system Arise in or adjacent to vertebra from remnants of primitive notochord Most commonly seen at the tip of the tail*** Also cervical spine Chordomas are considered potentially malignant Metastasis not seen in tail tumours Cutaneous metastasis reported in one chordoma from the cervical spine

Answer 1307

Cardiomyopathy – DCM, HCM and RCM Heart may appear enlarged Right ventricle may appear thin or flabby Fluid in the abdominal cavity, the pleural cavity, or both Globose heart

Answer 1308

Dental disease Salivary mucocoeles Ulcerations Neoplasia – squamous cell carcinoma! (fibrosarcoma, melanoma)

Answer 1309

Thrombocytopaenia: Cutaneous haemorrhage Melena Swollen vulva

Answer 1310

Xenobiotics are exogenous chemicals in the environment in air, water, food, and soil that may be absorbed into the body through inhalation, ingestion, and skin contact. =poison =toxin

Answer 1311

The basis of toxicology involves absorption, distribution, metabolism, and excretion (ADME). Distribution is typically via the bloodstream. The liver receives the portal circulation and is the organ most commonly involved in metabolism. Excretion is largely dependent on water solubility- Polar or aqueous-soluble agents tend to be excreted by the kidneys Lipid-soluble chemicals- More likely to be excreted via the bile, Accumulate in fat

Answer 1312

There are two phases of metabolism of toxins. Phase 1 generally produces derivatives ready for phase 2 metabolism, but can also produce metabolites that can be directly excreted without phase 2 Phase 1 includes Oxidation Reduction Hydrolysis An important Phase I enzyme is cytochrome P450- MOST abundant in centrilobular (zone three) hepatocytes Phase 2 principally involves conjugation.- Common conjugates include glucuronides, acetylation products, and combinations with glycine. Important differences in metabolic mechanisms exist between species: Cats lack forms of glucuronyl transferase, their ability to conjugate compounds is therefore compromised.

Answer 1313

Xenobiotics can be directly toxic Or Can be metabolised to non-toxic metabolites- Some species may be better at this: Dogs tolerate paracetamol, cats don’t- Glucuronidation Xenobiotics can be minimally or non-toxic but then metabolised to a toxic metabolite: Ethylene-glycol, Organophosphates

Answer 1314

ZONAL PATTERN Not specific however Hypoxia- hepatocytes around central vein furthest from supply of oxygenated blood and then show damage more Grossly it will not be clear whether centrilobular or periportal hepatocytes are affected Assume centrilobular as more likely pattern Important to differentiate from random- Viruses and some blood-borne bacteria

Answer 1315

Centrilobular necrosis = toxic metabolites Most common Pyrrolizidine alkaloid-containing plants- Ragwort Aflatoxins- Produced by fungi Amanita mushrooms Remember will have to rule out congestive heart failure- Chronic versus acute (chronic = chf) Typically more degeneration and less necrosis Peri-portal necrosis- Uncommon, Directly toxic straight from portal circulation, doesn’t need to be metabolised to have effect Midzonal necrosis- Rare Massive necrosis- Relatively specific Iron dextran Vit E / Selenium deficiency Xylitol

Answer 1316

Carbon monoxide (see lecture later today) Pig salt toxicity/water deprivation (see neuro lecture) Urea/ammonia toxicosis- Slurry tank not cleaned out prior to using as water tank?

Answer 1317

Brain Heart Lungs Liver Kidney

Answer 1318

Urine Stomach content Kidney Liver Blood Fat - chronic/fat soluble. Best place to test for PCBs (sea mammal predators have chronic depositions as they are lipid soluble)

Answer 1319

Ethylene glycol (EG) is a colourless, odourless alcohol with a sweet taste and is an active constituent of antifreeze Pathophysiology- Once ingested EG is rapidly absorbed by the gastrointestinal system and distributed by the bloodstream Metabolism – Gastric - mucosal alcohol dehydrogenase liver - serial oxidation by alcohol dehydrogenase and aldehyde dehydrogenase= Rapid metabolism resulting in severe anion gap metabolic acidosis, this is what causes problem Once converted to oxalic acid within 36 to 93 hours, calcium oxalate crystals precipitate in target tissues including kidneys, brain, heart and lungs.- Hypocalcaemia Renal azotaemia- Increased urea and creatinine, Low USG (however are often anuric) Renal damage is due to: acid metabolites of ethylene glycol, which can cause acute tubular necrosis, primarily of the proximal tubules deposition of calcium oxalate crystals, primarily in proximal tubule epithelium Neuro signs in farm animals- thyamine

Answer 1320

Diagnosis History, time of year, clinical signs Biochem, urinalysis and blood-gas results- Renal azotaemia Hypocalcaemia High anion gap metabolic acidosis Calcium oxalate crystals in urine Urine will fluoresce under UV light Urine for toxicology Cats that have progressed to azotaemia tend to have bad prognosis Post mortem- Bilaterally mildly enlarged kidneys Multifocal white streaking within cortex- Necrosis and calcification Histopathology of kidney and brain Tox testing – blood, urine, fresh kidney tissue

Answer 1321

Rodenticides can be split into following categories First-generation anticoagulant rodenticides: warfarin, chlorphacinone, diphacinone Second-generation anticoagulant rodenticides: brodifacoum, bromadiolone, difenacoum, difethiolone Bromethalin - neuro toxin Cholecalciferol – vitD3 analogue Pathogenesis and pathophysiology- Anticoagulant rodenticides inhibit vitamin K Vitamin K is a cofactor of both intrinsic and extrinsic pathways of secondary haemostasis Animals will bleed- Disorders of secondary haemostasis tends to present with :epistaxis, GI, cavities, suffusive compare disorders of platelets (primary haemostasis) – petechiation, ecchymoses

Answer 1322

Diagnosis Investigate bleeding CBC-Regenerative anaemia Blood smear-Regenerative anaemia, Normal number of platelets Buccal mucosal bleeding time- Normal (1ry haemostasis) Coagulation/clotting times- PT and aPTT will be raised Post mortem Haemorrhages into intestine and cavities Histopathology not rewarding Tox testing- Stomach content not always useful as can take several days to weeks from ingestion to manifest, Seen in heparinised blood and liver

Answer 1323

Vitamin D3 is also known as cholecalciferol Found in Rodenticides Human medications- Tables, Creams (psoriasis) Pathogenesis and pathophysiology: Rapidly absorbed and metabolized by the liver and kidney. The major toxic effects are due to the major metabolite, calcitriol (1,25-dihydroxycholecalciferol) Calcitriol enhances- Resorption of calcium from bone Absorption of calcium from the gut Proximal renal tubule reabsorption of calcium in the kidney Results in hypercalcaemia- Calcium deposits in soft tissue- Stomach, Kidney -> renal failure

Answer 1324

Diagnosis- Biochemistry and urinalysis- Renal azotaemia and hypercalcemia (not pathognomonic) Post mortem- Soft tissue mineralisation: Stomach wall, Serosal surfaces, Kidneys Histopath- Stomach and kidneys (can see mineralisation)

Answer 1325

NSAIDs typically inhibit COX COX enzymes required for multiple functions Eg: aspirin is an analgesic, anti-inflammatory and anti-pyretic but also given to reduce clotting - 1ry haemostasis, Very very mild increase in BMBT The primary toxic effects of NSAID are due inhibition of prostaglandins ->Vasoconstriction : in kidney-> renal failure (necrosis at renal pelvis), in stomach -> stomach ulcers

Answer 1326

Incomplete list of examples Xylitol Aflatoxins Amanita mushroom (amanitin) Blue-green algae (microcystin) Heavy metals-Copper (see later) Certain herbicides, fungicides, insecticides, and rodenticides. Paracetamol- Cats>>dogs Idiosyncratic drug reactions Diazepam Carprofen Methimazole Pathophysiology Liver failure- Raised ALT+ALP, Low albumin, Coagulopathies (2ry haemostasis), Jaundice (Increased Tbil), Hyperammonaemia (Hepatic encephalopathy, Ammonium biurate crystals in the urine), Multi-organ failure

Answer 1327

Copper plays a critical role as a cofactor: Cytochrome C oxidase - mitochondrial respiration Lysyl oxidase - connective-tissue maturation (collagen cross-linking) Superoxide dismutase - antioxidant defense Tyrosinase - melanin synthesis Ceruloplasmin - iron metabolism dopamine β hydroxylase - neurotransmitter biosynthesis In excess- Catalyzes free radical formation Accumulates intracellularly in the nucleus resulting in DNA damage and apoptosis Mechanisms of toxicity- Primary metabolic defect in hepatic copper metabolism- Bedlington terriers, autosomal recessive disorder of copper metabolism due to exon 2 deletion of COMMD1 gene causing progressive hepatic copper accumulation with age Altered hepatic biliary excretion of copper Excess dietary intake of copper Gross lesions Chronic changes – fibrosis, nodular regeneration, small liver Diagnosis: Histopath (centrilobular degeneration and fibrosis)- Special stains (rhodanine) for intracellular copper Fresh sections of liver for copper levels

Answer 1328

Typically an acute crisis secondary to inappropriate bolussing or sheep being fed or breaking into cattle feed Toxic to hepatocytes and erythrocytes- Liver failure Intravascular haemolysis Renal failure Haemoglobinuria Gross pathology- Liver variable Kidneys bilaterally dark red and slightly enlarged with dark red urine

Answer 1329

Normal acetaminophen metabolism: Phase I reaction via CYP450 -> toxic metabolite N-acetyl-p-benzoquinone-imine (NAPQI) Phase II reaction (conjugation) via either: Uridine diphosphate (UDP)-glucuronosyl transferase (glucuronidation) > excreted via bile and urine Phenol sulfotransferase (sulfation) > excreted via bile and urine Glutathione (GSH) (glutathione conjugation) > excreted via bile and urine Pathogenesis and pathophysiology of overdose: Phase II enzyme systems become saturated -> excess toxic NAPQI -> excessive oxidative stress and cell damage in blood oxidation of iron in haemoglobin and formation of methemoglobin (Fe2+ > Fe3+ = methaemoglobin) -> interference with oxygen transport -> cyanosis and brown mucous membranes denatured haemoglobin precipitates on erythrocyte membranes ->Heinz bodies oxidation and cross-linking of membrane proteins -> eccentrocyte formation NB: Heinz bodies and eccentrocytes not pathognomic, just means oxidative damage – rule out onion toxicity -> excessive oxidative stress and cell damage of hepatocytes Centrilobular hepatic necrosis

Answer 1330

Theobromine and caffeine Clinical signs- Polydipsia, vomiting, diarrhoea, abdominal distention, and restlessness. May progress to hyperactivity, polyuria, ataxia, rigidity, tremors, and seizures. Tachycardia, premature ventricular contractions, tachypnoea, cyanosis, hypertension, hyperthermia, bradycardia, hypotension, or coma may occur. Death is generally due to cardiac arrhythmias, hyperthermia, or respiratory failure. High fat content of chocolate products may trigger pancreatitis No specific lesions at necropsy.

Answer 1331

Unclear pathogenesis Renal failure

Answer 1332

Slug bait Neurological Very sudden onset

Answer 1333

Ataxia, bradycardia, hypothermia, vocalization, hypersalivation, vomiting, diarrhoea, urinary incontinence

Answer 1334

Contains persin Toxic to many species – birds and mammals Cardiotoxic – see next lecture

Answer 1335

Carbon monoxide (CO) will most commonly be encountered by animals and people in poorly ventilated enclosed spaces heated by combustion sources- intensive animal production facilities Also part of death in a fire, and produced by cars Odourless and colourless Pathogenesis- CO binds with high affinity to many ferrous heme-containing proteins. Hb has a 250-fold greater affinity for CO than for oxygen. CO competes with oxygen for binding to Hb and, by displacement of oxygen, reduces oxygen carrying capacity. Clinical signs in people- severe and persistent headache dizziness, weakness, nausea, vomiting, chest pain, shortness of breath, irritability, and altered mental status tachycardia, tachypnoea, hypotension impaired memory and cognitive and sensory disturbances Signs and necropsy in animals- Mass death Cherry red mucous membranes and organs

Answer 1336

As with small animals the liver is commonly involved in poisoning cases. In farm animals and equines this is often associated with toxic plants. The most commonly associated is ragwort. Pathogenesis and pathophysiology- Pyrrolizidine alkaloids- exists in the plant in two molecular forms toxicity occurs when these are converted by liver microsomal enzymes (cytochrome P-450 monooxygenases) Toxicity of PAs is due to centrilobular necrosis and antimitotic action Centrilobular necrosis with megalocytosis in the liver Typically a chronic disease- Fibrosis and biliary hyperplasia, regenerative nodules Clin path- Elevated liver enzymes Herbivores – photosensitisation - > skin ulceration Megalocytosis- Will see multiple and large nuclei as cells try to undergo mitosis but cannot

Answer 1337

Many toxins are cardiotoxic Plants- Avocado Foxglove (digitalis) Yew Rhododendron-Less acute, Only thing that makes goats vomit! Drugs: Ionophores- Coccidiostats/growth promoters Typically peracute- Plant material found in GIT Gross post mortem findings non-specific otherwise Histopath- Peracute/acute monophasic cardiomyofibre necrosis

Answer 1338

Native to North America Ornamental in UK Wilted/dried leaves toxic, not green Most commonly reported in horses Unknown toxin causes oxidative damage to erythrocytes Heinz body anaemia Haemolysis Methaemoglobin Haemoglobinuria Renal failure

Answer 1339

Native to UK Seeds (Autumn) and seedlings (Spring) toxic Most commonly reported in horses Atypical myopathy/seasonal pasture myopathy Contain hypoglycin A- inhibit acyl-CoA dehydrogenases, causing degeneration of type I muscle fibres Elevated CK Myoglobinuria Renal failure

Answer 1340

Native to UK Acorns (Autumn) and young leaves (Spring) toxic Most common in ruminants but can occur in horses Gallotannins are hydrolyzed to their active metabolites: tannic acid, gallic acid, and pyrogallol by fermentation in the rumen Toxic to renal tubules- Renal failure and haematuria Bind to endothelium resulting in endothelial damage -perirenal oedema, hydrothorax, ascite

Answer 1341

A positive reaction for heme on a dipstick occurs in the following situations: Haemorrhage (haematuria): This is the most common cause of a positive reaction. The reaction for heme on the dipstick is very sensitive and will detect heme associated with as few as 10 RBC/uL. Intravascular haemolysis (haemoglobinuria) Skeletal muscle injury (myoglobinuria) How to tell the difference Sediment exam If once urine is spun down and the urine is clear it is most likely haematuria Assess sediment for in tact RBCs If present is most likely a urinary (or repro) source UTI Neoplasia Pyo If after spinning remains red is either haemoglobinuria or myoglobinuria- Look at biochem and CBC Ammonium sulphate 80% will precipitate out haemoglobin not myoglobin

Answer 1342

Contains several toxins- Ptaquiloside Quercetin (carcinogenic) Thiaminase And a “bleeding factor” of unknown structure Thiamine deficiency Acute Horses Polioencephalomalacia Ruminants Acute- Direct inhibition of bone marrow--> pancytopenia ->haemorrhage and neutropaenic septicaemia Chronic- Co-infection with BPV, will result in GI or bladder tumours.

Answer 1343

Pathogenesis- Lush grass contains abundant L-tryptophan Not toxic on its own but converted by ruminal bacteria to 3-methylindole - Pneumotoxic, Interstitial pneumonia Clinical signs- Respiratory distress Foaming at the mouth 30% mortality Gross pathology- Diffuse widening of interlobular septa by fluid

Answer 1344

an exudate or other product of disease that replaces alveolar air, rendering the lung solid

Answer 1345

Elevated urae, kreatinie, usg and total protein is DEHYDRATION Increased SDMA, urea and creatinine- Azotaemia (term for the elevated levels) Uraemia is the clinical manifestation (of azotemia) -Halitosis, tongue ulcers, etc SDMA elevated earlier When have these signs Also test USG- Low USG indicates tubular loss Electrolytes- NaCL decrease K+ increases – blocked K+ decreases – cats with CKD Ca – Depends:, Hypo in ethylene glycol, end stage CKD, blocked, Hyper in AKI Phosphate – increases Urine protein- Increased with glomerular disease, UTI, canine HAC With glomerular disease will also see low albumin Kidneys produce EPO- Non-regen anaemia with CKD

Answer 1346

Key differences in small versus large animals Cat ALT and ALP have much shorter half life compared to dogs → smaller elevations are more clinically significant Canine steroid ALP isoenzyme is elevated with both drugs (corticosteroids, phenobarbital), chronic stress, and hyperadrenocorticism Bone ALP can increase with growth in young animals as well as patients with high osteoblastic activity (e.g. hyperparathyroidism) Colostrum is high in GGT → increases in calves: Can be used to check for passive transfer Also elevated in foals but not due to colostrum Others Bile acids and bile acid stimulation test- Liver function Shunts ( other markers will be normal as liver is being bypassed) Bilirubin Icterus/jaundice Cholesterol, albumin, urea and glucose- All low in liver failure as made here Coagulation factors (2ry haemostasis)- Clotting times/aPTT and PT increased in liver failure Think about this before biopsy!

Answer 1347

List what blood tube you would pick for common samples taken in small animal practice Biochem- Lithium heparin- Generally the orange top in small animals Also fine for haematology in exotics Haematology- EDTA- Generally the pink or red top in small animals Contaminating biochem sample will result in hyperkalaemia and hypocalcaemia Glucose- Run immediately inhouse Sodium fluoride/oxalate- Generally yellow top in small animals Clotting times (2ry haemostasis)- Run in house Sodium citrate- Generally the purple top in small animals Endocrine- Plain/gel tubes- Generally white or brown top in small animals Serum do lithium heprin before edta

Answer 1348

Haematocrit (HCT) is a calculated value- nRBCs x mean cell volume (MCV) Packed cell volume is what you measure Complete blood count versus haematology Start with nRBC/HCT/PCV If low = anaemia Then have to decide if regenerative or not- MCV and reticulocytes will increase MCV is the average size of the erythrocytes Reticulocytes are immature erythrocytes Regenerative = disease happening in blood and bone marrow can respond Non-regenerative = bone marrow disease, chronic illness especially CKD as kidneys make EPO Iron-deficiency- Microcytic hypochromic Low MCV and low MCHC Round and pale on smear Polychromatophils are the same thing as erythrocytes but stained differently

Answer 1349

Acanthocytes- Lipid disorders Liver disease Shearing injury- DIC, Cancers: Haemangiosarcoma Echinocytes- Prolonged storage (artefact) Schistocytes- Fragility (iron deficiency) Shearing injury- Haemangiosarcoma Spherocytes- IMHA:Regenerative anaemia Jaundice In-saline agglutination Coomb’s test

Answer 1350

Reticulocytes/polychromatophils/basophilic stippling- regeneration Heinz bodies- Oxidative damage Onions Paracetamol Red maple Not obvious with all stains- Methylene blue Howell-Jolly bodies- Normal/regeneration

Answer 1351

Cattle and dogs- Babesia Cats- Mycoplasma haemofelis: Not the same one as respiratory Camelids- Mycoplasma haemolamae

Pathology Flashcards

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