SA clinical pathology

Question 1

What liver features can be tested for by clinical pathology?

Answer 1

Hepatocellular injury -> leakage of enzymes
Cholestasis (reduced/blocked bile excretion) -> release of enzymes induced by retained bile
Hepatocellular function - decreased production or catabolism of substances
Hepatic portal circulation - decreased extraction of substances absorbed from GIT

Question 2

Where are liver enzymes found normally?

Answer 2

ALP and GGT - on hepatocyte cell membranes

ALT, AST and SDH - in hepatocyte cytosol (and AST in mitochondria)

Question 3

Which liver enzymes are there and what are they specific for?

Answer 3

ALT - largely liver specific (but also muscle), small animals
AST and LDH - liver and muscle
SDH and GLDH - liver specific in all species, used in large animals, SDH unstable
ALP and GGT - used in large animals as indicators of liver damage

Question 4

What does it mean if there are increased liver ‘leakage’ enzymes in the blood?

Answer 4

Indicates hepatocellular damage
Myocyte damage can cause mild increase of AST, LDH +/- ALT (check CK)
Artefact (haemolysis) can increase AST and LDH (check serum/plasma quality)
Magnitude of increase correlates with degree of hepatocellular damage but not with reversibility of injury, prognosis or hepatic function
Short half lives: days in dogs, hours in cats (so even small increases may be significant in cats)

Question 5

Which ‘cholestatic’ enzymes are there, used in small animals? What else can be used so assess if cholestasis?

Answer 5

ALP - good se for dogs but poor se for cats, scottish terriers have higher activities
GGT - more specific
Bilirubin
Bile acids - more sensitive
Cholesterol

Question 6

What forms of ALP are there?

Answer 6

2 isoenzymes: intestinal and non tissue specific (I-ALP not generally detected in plasma as short half life so lost in GI tract)
Measurable isoforms:
- Liver-ALP (L-ALP) - serum half life of approx 70h in dog and 6h in cat (so insensitive in cats)
- Bone-ALP (B-ALP) - usually causes only mild increases, negative prognostic marker in osteosarcoma
- C-ALP - unique to dogs, induced by corticosteroids, product of I-ALP gene but produced in hepatocytes

Question 7

What happens to senescent red cells to produce bilirubin?

Answer 7

Breakdown of haemorrhage to bilirubin in macrophages of reticula-endothelial system (tissue macrophages, spleen, liver)
Unconjugated bilirubin is transported in blood via albumin to the liver
Taken up by facilitated diffusion by liver and conjugated with glucoronic acid
Conjugated bilirubin actively secreted into bile then into intestine
In intestine glucorionic acid is removed by bacteria and bilirubin is converted to urobilinogen
Some of urobilinogen is reabsorbed from gut and enters portal blood
Some of this participates in the enterohepatic urobilinogen cycel
Remainder of urobilinogen is transported in blood to kidney, converted to yellow urobilin and excreted

Question 8

Types of hyperbilirubinaemia?

Answer 8

Prehepatic - secondary to haemolytic, check for anaemia
Hepatic - can be due to decreased bilirubin uptake, conjugation and excretion (so hepatocyte dysfunction and intrahepatic cholestasis)
Post-hepatic - secondary to obstruction of extra hepatic bile duct, serum cholesterol often high, ultrasound useful

Question 9

How is bilirubin measured?

Answer 9

Total bilirubin
Conjugated bilirubin (=direct bilirubin)
Unconjugated = Til-DirBil (=indirect bilirubin)

Question 10

Clinical signs of hyperbilirubinaemia?

Answer 10

Jaundice persists long after liver function turned to normal due to delta-bilirubin bound to albumin
If jaundice is due to delta-bilirubin there will be no bilirubinuria

Question 11

Liver functions?

Answer 11

Detoxification
Synthesis of cholesterol, bile acids, plasma proteins, clotting factors
Breakdown of RBCs
Metabolism of carbohydrates, lipids and amino acids
Removal of bacteria
Storage of glycogen, iron, copper, vitamins

Question 12

What markers are there of decreased hepatocellular function?

Answer 12

Decreased uptake and excretion of bilirubin and bile acids - increased (unconjugated) bilirubin and bile acids
Decreased conversion of ammonia to urea - increased ammonia, decreased urea
Decreased synthesis of metabolites - decreased albumin, cholesterol coagulation factors and inhibitors, glucose (but hypoalbuminaemia, hypoglycaemia, hypocholesterolaemia are insensitive markers for decreased liver function)
Decreased synthesis of coagulation proteins - decreased fibrinogen, increased PT and PTT
Decreased immunologic function - decreased clearance of toxins and antigens -> systemic stimulation -> increased Igs

Question 13

What markers are there of alteration of hepatic blood flow (PSS)?

Answer 13

Decreased uptake and excretion of bile acids - increased bile acids (bilirubin not usually increased as major problem is the bile acids re-uptake from blood)
Decreased conversion of ammonia to urea - increased ammonia
Decreased immunologic function - decreased clearance of toxins and antigens -> systemic stimulation -> increased Igs

Question 14

Where is ammonia produced and what happens to it?

Answer 14

Produced in GIT by protein digestion or bacteria metabolism
Enters liver via portal vein
Uptaken by hepatocytes to synthesise urea, amino acids, proteins
Urea diffuses to sinusoidal blood or bile canaliculi and is excreted through kidneys or intestine

Question 15

Things to note when measuring blood ammonia?

Answer 15

Relatively insensitive
Only significant if raised (hepatic encephalopathy)
Not stable in vitro so should be measured immediately after blood sampled
Elevated in:
- congenital and acquired porto-systemic shunts and liver failure

Question 16

Where are bile salts produced and what happens to them?

Answer 16

Produced by hepatocytes
Released into biliary system and then intestine - allow fat absorption and digestion
>90% then reabsorbed from ileum, enter portal vein, return to liver, re-circulate
Small amounts lost in faeces, replaced by liver

Question 17

What can increased bile acids in the blood mean?

Answer 17

Reduced uptake/excretion by hepatocytes - reduced hepatocellular mass, impaired hepatocyte function
Disruption of enterohepatic circulation - portosystemic shunts, cholestasis/bile obstruction
No point measuring BA if bilirubin already increased (BA more sensitive)

Question 18

Interpretation of fasting SBA?

Answer 18

> 25-30mmol/L are abnormal and indicate hepatobiliary pathology - can’t differentiate between cholestasis and liver failure
<25-30mmol/L cannot completely exclude portosystemic shunt, perform bile acid stimulation test (BAST) if still suspecting hepatic pathology

Question 19

Interpretation of post prandial SBA? How to do it?

Answer 19

BA stimulation test/dynamic BA
Take resting sample
Fatty meal
Post-prandial sample 2h after feeding
>25-30mmol/L is abnormal and indicates hepatobiliary pathology - can't differentiate between cholestasis and liver failure

Question 20

What extra hepatic diseases can cause elevation in liver enzymes?

Answer 20

Hypoxia
GI and pancreatic disease
Endocrine diseases (fat or glycogen accumulation)
Sepsis 
= 'reactive hepatopathies'

Question 21

How to determine if raised liver enzymes is due to ‘reactive hepatopathy’ due to extra hepatic disease?

Answer 21

Most have normal bile acids
Other markers of liver function will be normal - unless affected by primary disease
Bile acids may be markedly elevated in sepsis/SIRS/endotoxaemic shock

Question 22

What haematology may be seen in liver disease?

Answer 22

Microcytosis - portosystemic shunts or severe liver insufficiency, likely due to altered iron transport or metabolism
Ovalocytes (elliptocytes) are frequently seen in cats with hepatic lipidosis
Acanthocytes - lipid disorders, disruption of normal vasculature (e.g. hepatic haemangiosarcoma)

Question 23

Urinalysis in liver disease?

Answer 23

Often unremarkable but may see:

• isosthenuria or inappropriately low USG
• bilirubinuria (more than 2+ in dogs, any in cats)
• ammonium bitrate crystals or uroliths (40-70% of patients with portosystemic shunts)

Question 24

Functions of the pancreas?

Answer 24

Exocrine acinar cells (98%) - secrete enzymes involves in initial digestion of food
- proteases (trypsin, chymotrypsin, elastase)
- lipases
- amylases
- high conc of bicarbonate in secretions
- aids B12 and zinc absorption
- antibacterial activity
- intestinal mucosal modulation
- proteases stored as inactive zymogens
Endocrine islet cells (2%) - secrete insulin and glucagon

Question 25

Tests for exocrine pancreas integrity?

Answer 25

Amylase and lipase tests - identify injury to pancreatic cells (increases most often due to pancreatitis), pancreatitis should be based on a combo of these tests with compatible clinical and imaging signs (abdominal ultrasound) DGGR - proven to correlate well with more specific tests and clinical pancreatitis, cut offs for pancreatitis diagnosis: - >34 U/L in cats - >216 U/L in dogs Canine pancreatic lipase (cPL) - considered more specific and more sensitive than lipase and amylase, snap test available TLI (trypsin like immunoreactivity) - used in dogs, cats, horses (species specific assays), detects trypsinogen, trypsin and trypsin bound to protease inhibitors, use in animals with clinical signs of maldigestion/malabsorption, high se and sp for exocrine pancreatic insufficiency, less useful fro pancreatitis, serum TLI < 2.5mg/L in dogs, < 8mg/L in cats

Question 26

Amylase - function, half life, species used in?

Answer 26

``` Catalyses hydrolysis of complex starches Short half-life (hours) Salivary and intestinal not found in serum More useful in dogs than other species Can increase due to decreased GFR ```

Question 27

Lipase - function, half life etc?

Answer 27

Catalyses hydrolysis of triglycerides Very short half-life (2 hours) Mostly from pancreas Can increase (mildly) due to decreased GFR Different tests have different positive and negative predictive value

Question 28

Diagnosis of pancreatitis?

Answer 28

Elevation in lipase (and amylase) - suggestive but other causes possible, higher increase=higher likelihood, degree of increase doesn't = severity of disease Need compatible clinical signs Additional tests - PLI (specific pancreatic lipase), ultrasound, fluid analysis, biopsy

Question 29

Suggested criteria for diagnosis of acute pancreatitis in dogs?

Answer 29

Absence of surgical disease on abdominal radiographs or analysis of abdominal fluid And abdominal ultrasound with evidence of primary pancretitis And one or more of the following: - Spec-cPL >400ug/L - Positive SNAP-cPL - Gross lipaemia - Serum PE-1 >17.24 ng/ml - Total lipase >3x the upper reference interval

Question 30

Indications for cytology?

Answer 30

``` Lesion (nodule, mass, plaque) palpable externally or seen on imaging Organomegaly Cavitary effusion Cancer staging PUO ```

Question 31

Problems reducing cytology sample quality?

Answer 31

Ruptured cells - incorrect sampling or smearing technique | Inadequate staining

Question 32

Identifying cell types on cytology?

Answer 32

Inflammatory cells - neutrophilic, eosinophilic, lymphocytic, histiocytic, mixed Tissue cells - expected from organ aspirated, abnormal cells

Question 33

Normal cytology of skin and subutaneous tissue?

Answer 33

Few keratinocytes Scant fat Rare sebocytes

Question 34

How to assess neoplastic cells and malignancy from cytology?

Answer 34

Cell arrangement - discrete or cohesive - any cytoarchitecture Cell shape - round, polygonal, spindle Criteria of malignancy - hypercellularity (in mesenchymal tumours) - pleomorphism (anisocytosis, anisokaryosis) - high/variable N:C ratio - multinucleation - karyomegaly - mitoses (especially if atypical) - nuclear moulding (rapid cell growth) - large, angular, or variably sized nucleoli Minimum of 3 criteria to be classified as malignant (nuclear are stronger) - adapt depending on specific organ/cell type, allow some with inflammation and in histiocytes If absent criteria of malignancy -> benign or well differentiated malignant

Question 35

How do round cell tumours, epithelial tumours and mesenchymal tumours typically present on cytology?

Answer 35

Round cell tumour - 'sea' of round, discrete cells Epithelial tumour - 'islands' of cohesive polygonal cells Mesenchymal tumour - spindle cells with indistinct edges embedded in extracellular 'matrix'

Question 36

What round cell tumours are there?

Answer 36

``` Histiocytoma Plasma cell tumour Mast cell tumour Lymphoma Transmissible venereal tumour (not in UK) ```

Question 37

Histiocytoma - Typical presentation? Cytology?

Answer 37

Dome shaped, alopecia, may be ulcerated Tend to regress in a few weeks Often (but not only) in young dogs Cytology - light blue cytoplasm fading into the background, small lymphocytes often present and may predominate at later stages, sometimes difficult to differentiate from plasma cell tumour and lymphoma

Question 38

Histiocytic sarcoma - cytology?

Answer 38

Arises from interstitial dendritic cells Usually marked cell pleomorphism with karyomegaluy and multinucleation Localised or disseminated

Question 39

Lymphoma - cytology?

Answer 39

Round cells with high nucleus to cytoplasm ratio Large blasts (larger than a neutrophil) Monomorphic population

Question 40

Mast cell tumour - cytology?

Answer 40

Magenta granules in the cytoplasm - sometimes don't stain well with Diff Quik (send some unstained slides to lab) Poor granulation can be due to poor differentiation (usually means a more aggressive tumour)

Question 41

Plasmacytoma - cytology?

Answer 41

Cutaneous plasmacytomas are usually benign Can be well differentiated to pleomorphic (most commonly) Deep blue cytoplasm, perinuclear halo, eusinophilic borders Round, eccentric nucleus

Question 42

Types of keratinising lesions?

Answer 42

Epidermal/follicular cysts - cysts lined by normal keratinised epithelium, keratin accumulates in centre Hair follicle tumours - many types, mostly benign, often cytologically identical to cysts, sometimes basaxoid cells

Question 43

Trichoblastoma - what is it? cytology?

Answer 43

Benign skin tumour Scant amount of cytoplasm Uniform nuclei

Question 44

Sebaceous adenoma - cytology?

Answer 44

Raised cauliflower alopecic lesions Clusters of cohesive heavily vacuolated cells Cannot differentiate from hyperplasia on cytology

Question 45

Hepatoid gland tumour - where? cytology?

Answer 45

Usually benign Perianal or along thighs Cutaneous Clusters of 'hepatic' cells - similar to hepatocytes (large polygonal shaped cells, abundant pink-blue granular cytoplasm, prominent single nucleolus) Surrounded by few 'reserve' cells - smaller and higher N:C ratio and oval nuclei

Question 46

Squamous cell carcinoma - cytology?

Answer 46

Polygonal cells with variable tendency to cohesion Typically marked pleomorphism Often secondary neutrophilic inflammation

Question 47

Anal sac adenocarcinoma - cytology?

Answer 47

Classically 'naked nuclei' appearance Often cells form rosettes and 'rows' Sheets of bland looking cells but high metastatic potential!

Question 48

Most common soft tissue sarcomas in dogs and cats?

Answer 48

``` Dogs: - perivascular and nerve sheath tumour - fibrosarcoma Cats: - fibrosarcoma/injection site sarcoma ```

Question 49

What tumours are 'confusing' as not easily classified as round, epithelial or spindle?

Answer 49

Endocrine and neuroendocrine tumours Histiocytic sarcoma, chondrosarcoma, osteosarcoma - may be round or spindle Melanoma: - well differentiated melanocytes are stellate - undifferentiated melanocytes may be fixate, round, cuboidal with some tendency to cohesion

Question 50

Are melanomas usually benign or malignant?

Answer 50

Usually benign and well differentiated in haired skin | Often malignant in nail beds, oral cavity

Question 51

Lipoma - cytology?

Answer 51

Can't differentiate from 'normal' subcutaneous adipose tissue

Question 52

Where are erythropoietin and renin synthesised and where is vitamin A activated?

Answer 52

Erythropoietin: peritubular interstitial cells Renin: juxtaglomerular cells Vitamin D activation: proximal tubular cells

Question 53

What electrolytes/substances and conserved and excreted by a healthy kidney?

Answer 53

Conserve: - water - amino acids/proteins - glucose - bicarbonate - Na+ and Cl - Mg2+ and Ca2+ Excrete: - urea - creatinine - K+ - H+ - PO4 - ketones and lactate - bilirubin - haemoglobin and myoglobin

Question 54

What is not filtered by glomerlar filtration and what is it restricted by?

Answer 54

Cells, proteins larger than albumin and most lipoproteins Restricted by: - size - charge - albumin is size of pores but negatively charged

Question 55

Which tests of renal function are there? What are they all useful to assess?

Answer 55

Biochemistry: nitrogenous waste excretion (urea and creatinine), degradation of lipase and amylase, electrolyte balance Urinalysis Haematology: erythropoietin secretion Blood gas analysis: acid base balance (pH, BE, HCO3)

Question 56

How can GFR be measured?

Answer 56

Directly with plasma clearance of creatinine or iohexol - impractical Indirectly - urea and creatinine SDMA

Question 57

How much urea and creatinine is normally reabsorbed in the kidney?

Answer 57

Urea: up to 40% Creatinine: not reabsorbed, a bit secreted

Question 58

Causes for increased blood urea?

Answer 58

Decreased GFR Mild increases: - upper GI haemorrhage: protein catabolism, hypovolaemia/dehydration - high protein diet - recent meal - catabolism (fever, starvation, corticosteroids)

Question 59

Causes for decreased blood urea?

Answer 59

``` Severe liver disease or portosystemic shunt Low protein diet Aggressive fluid therapy PUPD - cause and effect Young animals Deficiency of enzymes in urea cycle ```

Question 60

Causes of increased and decreased blood creatinine?

Answer 60

``` Increase: - decreased GFR - high muscle mass (mild increase) - high dietary protein - non creatinine chromagens Decrease: - reduced muscle mass - usually not clinically significant ```

Question 61

Define azotaemia and uraemia?

Answer 61

``` Azotaemia = increased creatinine and/or urea Uraemia = complex of clinical signs seen in patients with renal disease: V+, D+, anorexia, weight loss, anaemia, ulcerative stomatitis, muscle tremors, convulsions, coma ``` All uraemic patients are azotaemic but not vice versa

Question 62

Causes of pre-renal azotaemia? Clinical signs/pathology/how can you tell it is prerenal?

Answer 62

Dehydration or decreased CO (due to decreased blood flow to kidneys): - clinical evidence of dehydration and/or hypovolaemia - maximally concentrated USG (>1.030 in dogs, >1.035 in cats) - urea often increased more than creatinine - should respond to fluid therapy Increased ammonia load (high protein diet, or GI haemorrhage) - increased urea but not creatinine - maximally concentrated USG - signs of iron deficiency possible

Question 63

Causes of renal azotaemia? Clinical signs/pathology/how can you tell it is prerenal?

Answer 63

Cause: decreased functional nephrons Variable USG: - isosthenuria (1.008-1.012) when >66% of nephrons lost - suboptimal USG (>1.012 but <1.030 in dogs and <1.035 in cats) - falls progressively - cats can lose concentrating ability later than dogs

Question 64

Causes of post renal azotaemia? Clinical signs/pathology/how can you tell it is prerenal?

Answer 64

Urinary tract rupture or blockage -> failure of urine output Hyperkalaemia If ruptured bladder: - creatinine in abdominal fluid > blood

Question 65

How good are urea and creatinine as markers of renal function?

Answer 65

Insensitive - only azotaemia when >75% of functional nephrons lost

Question 66

What is SDMA produced from? Is it filtered by the kidneys? Benefits for kidney disease? When to measure? RI?

Answer 66

Produced from intranuclear demethylation of L-arginine Freely filtered by glomerulus More se and sp than creatinine: - not influenced by muscle mass - increases with 40% reduction of GFR Measure when creatinine is normal or borderline to identify animals in IRIS stage 1/2 with absent or milf clinical signs RI <14ug/L (+1 in puppies, kittens, greyhounds)

Question 67

What electrolyte changes are seen with kidney disease?

Answer 67

Hyperphosphataemia: - small animals have a high phosphate intake - exception is horses as low diet P so tend to be hypo Hyper or hypokalaemia: - increased with acidosis, decreased urine output, marked decreased nephrons, anuria/oligura (AKI), bladder rupture, obstruction - decreased with increased urinary losses (esp CKD), decreased intracellular stores, GI losses Hypochloraemia: - increased renal loss (follows Na) - GI loss with vomiting Hyper or hypocalcaemia - hyper in horses - hyper in low % of smallies (usually only tCa) - most commonly hypo in smallies as decreased vit D and alimentation and tissue deposition

Question 68

What does it mean if the USG is hyposthenuric?

Answer 68

Requires functioning nephrons Diluted by kidneys Typically ADH problem

Question 69

When is a suboptimal USG significant? Cause?

Answer 69

``` If low USG + dehydration/azotaemia First look for non kidney causes: - lack of aldosterone or ADH - diuretics, glucocorticoids, glycosuria, medullary washout, pyelonephritis - low urea, Na or K, or high Ca If not, renal disease likely ```

Question 70

Proteinuria: When is it significant? Causes?

Answer 70

``` Small amounts up to +1 may be normal More significant if low USG Causes: - glomerular damage (renal) - protein overload to glomerulus (pre-renal) or urinary tract inflammation (post-renal) ```

Question 71

Urine protein:creatinine ratio: Why is this useful? Reference range for dogs and cats? What does it suggest?

Answer 71

Measure of proteinuria independent of urine concentration >0.5 (dogs) >0.4 (cats) = proteinuric 0-2-0.5 - borderline Elevated ratio in absence of an active sediment or hyperproteinaemia is a strong indicator of renal (often glomerular) disease

Question 72

Glycosuria: When seen? Significance?

Answer 72

Seen with serum glucose >10mmol/L in dogs and >16.6mmol/L in cats If serum glucose normal = renal glycosuria (failure of tubular reabsorption)

Question 73

What is the normal urine pH for dogs and cats? What does it mean if different?

Answer 73

Usually 5.5-7 Low with metabolic acidosis Can be inappropriately high with metabolic acidosis due to tubular dysfunction Alkaline due to UTI with urease producing bacteria

Question 74

What are casts un urine? Significance?

Answer 74

Cylindrical moulds of tubules composed of mucoproteins +/- cells Occasionally hyaline and granular casts may be normal Granular, cellular and waxy indicate tubular damage

Question 75

Crystals in urine: How significant?

Answer 75

Fresh urine: likely developed in vivo Stored urine: can precipitate post collection Lots of normal animals have crystalluria

Question 76

What types of crystals are there in urine? Significance? When formed?

Answer 76

Struvite: - magnesium ammonium phosphate - UTI, urolithiasis or normal - form in alkaline urine and in vitro Amorphous: - urate in acidic pH: no clinical significance - phosphate in alkaline pH, no clinical significance Calcium oxalate di-hydrate: - can be normal - can form in vitro - can be seen with ethylene glycol toxicity but not pathognomic Calcium oxalate monohydrate: - hyperoxaluric disorders or hypercalciuria (e.g. ethylene glycol toxicity or ingestion of oxalate rich foods like peanut butter) Ammonium bitrate or uric acid: - portosystemic shunts, liver disease, dalmatians Cystine: - associated with metabolic defect in tubular resorption of cystine (bulldogs)

Question 77

Normal distribution of electrolytes?

Answer 77

ECF: Na, Cl, HCO3 ICF: K, P, proteins

Question 78

Role of sodium? Causes of change? Controlled by?

Answer 78

``` Major cation in ECF responsible for preservation of electroneutrality - each Na ion balanced by an anion (2/3 Cl, bicarbonate) Maintains water in the body Usually narrow range Altered due to: - loss of Na and water (volume depletion) - loss of water alone (dehydration) Regulation of volaemia via RAAS Regulation of osmolarity via ADH ```

Question 79

RAAS system?

Answer 79

Low BP, low perfusion pressure, renal ischaemia, low Na in DCT, sympathetic stimulation -> renin synthesis Renin enzyme for angiotensinogen -> ANGI ANG 1 -> ANG 2 -> Vasoconstriction -> increased BP -> Aldosterone -> Na and water retention, K loss -> increased BP

Question 80

ADH activation and action?

Answer 80

Increased blood osmotic pressure -> detected by osmoreceptors in hypothalamus -> ADH and thirst -> increases permeability of collecting duct -> water reabsorbed to prevent further dehydration Thirst -> drinking reduces blood osmotic pressure

Question 81

Causes of hyponatraemia?

Answer 81

``` Loss: - V+, sometimes D+ - kidneys (tubulopathy) - hypoadrenocorticism (no aldosterone) - loss into an effusion - iatrogenic (thiazides, furosemide) Volume overload: - CHF - (end stage renal failure) - iatrogenic Increased plasma osmolarity: - severe hyperglycaemia - mannitol ```

Question 82

Reference for hypernatraemia in dogs and cats? Treatment?

Answer 82

>160mmol/L in dogs >165mmol/L in cats >170mmol/L is life threatening If chronic must correct slowly (too quick can cause CNS oedema) low sodium fluid - 5% glucose, 0.45% NaCl Furosemide as last resort?

Question 83

Causes of hypernatraemia?

Answer 83

Most commonly due to loss of fluid with concurrent decreased intake or deficient ADH responses ``` Hypotonic fluid loss (most common): - GI losses - renal failure - post-obstructive diuresis - any cause of polyuria (DM, Cushing's) Free water loss: - heat stroke - pyrexia - diabetes insipidus deprived water - inadequate/inability to access water - adipsia (mini Schnauzers and cats) Excessive intake (uncommon): - incorrectly mixed milk/electrolyte solutions without water access Excessive reabsorption: - hyperaldosteronism Iatrogenic: - fludrocortisone - sodium phosphate enemas ```

Question 84

What controls the K concentration in plasma? What happens to it?

Answer 84

K plasma concentration controlled by insulin, aldosterone and SNS Freely filtered at renal glomerulus and then reabsorbed K higher in serum than plasma

Question 85

Reference for hyperkalaemia? Clinical signs?

Answer 85

``` K > 5.5mmol/L Muscle weakness Cardiac abnormalities (normally if >7.5) Bradycardia Bradyarrhythmias - atrial standstill, life threatening conduction abnormalities ```

Question 86

Causes of artefactual hyperkalaemia?

Answer 86

Relatively common Postal/aged samples: - cell lysis - esp if leucocytosis and/or thrombocytosis K+ EDTA contamination: hyperkalaemia, hypocalcaemia, low ALP

Question 87

Causes of true hyperkalaemia?

Answer 87

``` Decreased urinary excretion: - urethral obstruction - bladder/UT rupture - anuric/oliguric renal failure - hypoadrenocorticism (lack of aldosterone) Drugs: - beta blockers, ACE-I, and K sparing diuretics in combo with K supplementation Translocation ICF -> ECF: - insulin deficiency in ketoacidotic DM - tumour lysis syndrome - extensive crush/reperfusion injuries - necrosis-large thrombi Increased intake: - iatrogenic - excessive supplementation ```

Question 88

Treatment for hyperkalaemia?

Answer 88

``` IVFT with K free or K depleted fluids Saline +/- 5% glucose Insulin and glucose? Calcium gluconate: - if cardiac effects - monitor on ECG Treat primary disease - correct acidosis ```

Question 89

Reference for hypokalaemia? Clinical signs?

Answer 89

``` K < 3mmol/l Clinical signs: - muscle weakness - PU/PD, impaired urine concentration - anorexia - ileus - constipation Anorexia will always lead to hypokalaemia as there is always some loss of K ```

Question 90

Causes of hypokalaemia?

Answer 90

``` Decreased intake: - anorexia - fluid therapy with K depleted fluids Translocation ECF -> ICF: - insulin - glucose containing fluids - catecholamines Increased loss: - gastrointestinal (vomiting, diarrhoea) Urinary - CRF in cats - diet-induced hypokalaemic nephropathy (low K, urinary acidifying diets) Post obstructive diuresis (esp cats) Mineralocorticoid excess: - HAC (more common if adrenal dependent) - primary hyperaldosteronism Drug therapy: - loop and thiazide diuretics - penicillins (unadsorbable anions increase lumen electronegativity) ```

Question 91

Feline hypokalaemia myopathy: What is it?

Answer 91

Sudden onset myopathy Often associated with elevated creatinine Inherited form in Burmese cats

Question 92

What is phosphate regulated by?

Answer 92

PTH promotes phosphate release from bone and excretion by kidneys

Question 93

Causes of hyperphosphataemia?

Answer 93

``` Failure to excrete: - decreased GFR (pre-renal) - renal failure (esp chronic) - UT obstruction/rupture Increased release from bone: - young animals - (osteolysis) - feline hyperthyroidism Increased intake/absorption - high phosphate diet - hypervitaminosis D - mild post-prandial Increased renal reabsorption - primary HYPOparathyroidism (PTH has a phosphaturic effect) Spurious: - haemolysis: Tends to be mild - monoclonal gammopathy Tumor lysis syndrome, soft tissue trauma ```

Question 94

Causes of hypophosphataemia?

Answer 94

``` Anorexia (cat) Shift from ECF to ICF: - insulin administration Decreased renal reabsorption GI loss (vomiting/diarrhea) Primary HYPERparathyroidism (PTH is phosphaturic) Reciprocally in hypercalcaemia of malignancy Hepatic lipidosis in cats Cushing’s in dogs ```

Question 95

Forms of calcium in the body?

Answer 95

Total calcium: - free calcium is biologically active (50% of total): regulated by PTH, vitamin D (calcitriol) and calcitonin - protein bound (most bound to albumin, 40%) - bound in other complexes (phosphate, bicarb) Free calcium is unstable so must be measured ASAP

Question 96

How to calculate corrected Ca for dogs? Problem?

Answer 96

Measured Ca - alb + 3.5 | Need to convert units and not reliable in patients with kidney disease

Question 97

Clinical signs of hypercalcaemia?

Answer 97

PUPD

Question 98

Causes of hypercalcaemia?

Answer 98

``` Malignancy: - LYMPHOPROLIFERATIVE DISEASES - anal sac adenocarcinoma Renal failure Primary hyperparathyroidism Hypoadrenocorticism Bone lesions Young, growing animals Vitamin D toxicity Cholecalciferol rodenticide toxicity Artefact: lipaemia, hypovolaemia, haemolysis ```

Question 99

Ddx acronym for hypercalcaemia?

Answer 99

``` H = Hyperparathyroidism, houseplants, hyperthyroidism (cats), HHM A = Addison’s, Vit A R = Renal disease, raisins (dogs) D = Vitamin D toxicosis, granulomatous dz I = Idiopathic (cats), infections, inflammatory O = Osteolytic N = Neoplasia, nutritional S = Spurius, Schistomosiasis ```

Question 100

Clinical signs of hypocalcaemia?

Answer 100

``` Muscle tremors, twitches, cramps Seizures Facial pruritus in cats Lethargy, anorexia Restlessness, behavioural changes ```

Question 101

Should you always supplement for hypocalacemia?

Answer 101

Not if due to hypoalbuminaemia (low total but normal ionised Ca)

Question 102

Causes of hypocalcaemia?

Answer 102

``` Hypoalbuminaemia (but free Ca is WRI) Ethylene glycol toxicity (precipitates in tubules) Intestinal malabsorption (dog) Acute pancreatitis (dog) Eclampsia/puerperal tetany Idiopathic hypoparathyroidism Renal disease EDTA or citrate tube Iatrogenic hypoparathyroidism: - drugs (anticonvulsants, glucocorticoids, phosphate enemas) - nutritional - post thyroidectomy in cats ```