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Flashcards in Pathology Deck (90)

What are the four factors on which the degree of cellular injury depend?

1. Dose of injurious agent - eg.  the more virus or bacteria assaulting the cell, the worse the injury could be;

2. Duration of agent's action - the longer, the worse the effect, typically

3. Vascular flow & nutrient supply - eg., oxygen from blood. Typically, cells in tissue that are poorly supplied with blood tend to be more susceptible to infection, but in cases where the antigen/pathogen travels via blood, then those cells that reside in richly vasculated areas like lung, liver, heart, kidneys can be worse affected.

4. Cell Type - highly active/metabolic cells eg. hepatocytes, proximal convoluted tubular epithelium of kidney & cardiac myocytes most susceptible to injury, compared with less metabolically active cells like tenocytes of tendon.


What five stimuli cause cellular injury?

i/ ATP-depletion (ATP needed for cell function). This can occur with:
a/ damage to mitochondrial membrane, which would halt metabolism and thus deprive the cell of ATP & thus result in cell death;
b/ damage to lysosome membrane, so that cellular components would be lysed;
c/ damage to cell’s plasma membrane itself, leading to loss of cellular contents into interstitial fluid.

ii/ Accumulation of waste products like lactate

iii/ Increased cell metabolism - non-renal/cardiac/hepatic cells can also turn on their metabolism to meet demands 

iv/ hypoxia of cell

v/ Pressure changes on cellular organelles - eg., when organelles degenerate, ↑ pressure on the cell inside (basically the rotting/detritus of organelles jams up cell cytoplasm)


What are the five main types of cellular degeneration? 

Degeneration occurs when observable change can be detected within the individual cell.

1. Cellular swelling - mildest, earliest detectable degenerative change due to damage to cell membrane; first stage of cell injury; might be momentary or quickly becoming serious damage.

2. Hydropic - more severe/advanced form of cellular swelling. Cells might swell up like balloon prior to destruction OR vacuole/bleb of fluid develops inside cytoplasm. Looks progressively more swollen & irregular in shape.

3. Cellular fatty change - accumulation or increase of fatty substances within cyctoplasm of specific cells eg., liver, kidney, heart parenchyma, but DOES NOT include accumulation of fat in normal fatty stores.

4. Mucoid (myxoid or myxomatous) - Two types:
I. Extracellular - tend to show faint bluish tinge in H&E stains (check on this for examples)
II. Changes in ground substance aka matrix produced by fibroblasts in connective tissue or epithelial tissue (excessive secretion of mucin). 

5. Hyaline - always pathological, means “glassy”. 
Microscopically, degeneration appears amorphous, staining pinkish red with eosin in H&E.
Intracellular - Eg. degeneration of skeletal muscle
Extracellular - Eg. hyaline protein casts in urine


What are the causes and significance of cellular-swelling degeneration, and what does it look like grossly & microscopically?

CAUSED by influx of H20 into the cell, caused by anoxia & mild toxins (they cause plasma-membrane damage);

SIGNIFICANCE: leads to very subtle change, not so different from early post-mortem or agonal change.

GROSSLY, the tissue would appear paler than normal, and upon cutting, the tissue might bulge because the cells within are swollen.

MICROSCOPICALLY, you would see moderate swelling of cells.


What are the causes and significance of hydropic degeneration?

CAUSE: Excess fluid transferred to ER, which swells, fragments & leaves fluid vacuole in cytoplasm.
SIGNIFICANCE: might indicate viral infection, eg., FMD. Common in metabolically active cells, and those that have well-developed ion pumps.



ATP Production decreases
⬇(Cell membrane damage)

Na+ & H2O move into cell

K+ moves out of cell

Osmotic pressure ↑

More H2O moves into cell

Cisterae of ER distend, rupture & form vacuoles

Ruptured ER & vacuoles merge Extensive vacuolation



What are the causes of cellular fatty change?

I. Dietary & Metabolic:
i/ Starvation - liver is overwhelmed by ↑ mobilisation of fat, stored as neutral fat in liver.
ii/ Overeating - dietary intake is greater than energy expenditure, so fat is temporarily stored prior to movement to body-fat stores.
iii/ Lipotrope derangement - these are basically transporters of fats out of liver. They’re amino acids that help conjugate fat with proteins to form lipoprotein that’s excreted out of cell. Choline & methionine deficiency in diet can lead to fatty change.
(metabolic disease lead to DIFFUSE fatty change)

II. Anoxia:
i/ Anaemia - due to haemhorrage or haemolysis
ii/ Circulatory disorders - eg. ischaemia, chronic venous congestion (leads to ZONAL fatty change with “nutmeg” liver, in periportal areas & congestion in periacinar areas).

III. Toxins: more severe form of cellular swelling when toxins cause fatty change in liver.
i/ bacterial & fungal toxins - produced in bloodstream from circulating bacteria or produced elsewhere & absorbed into bloodstream;
ii/ chemical toxins - CCl4, phosphorous, arsenic, lead
iii/ some plant & fungal toxins - cause fatty change in v. early stages of poisoning.


What are the different types of hyaline degeneration?

Intracellular - Eg. degeneration of skeletal muscle
Extracellular - Eg. hyaline protein casts in urine
Eg. hyaline membranes in lung - protein escaping into
alveoli, impairing gas exchange.


What is fibrinoid degeneration?

Partly degenerated muscles & elastic fibres; partly increased amount of protein ground substance around degenerated fibres; appears fibrin-like red smudging - suggests either local hypersensitivity reaction or hypertension in the blood vessels.


What is amyloid degeneration?

Polymerisation of abnormal peptides into fibrillar proteins from wide variety of sources including albumin, immunoglobin, acute phase proteins & hormones.

β-pleated fibrils (sheets) make up 95% of amyloid - they’re insoluble and can’t be removed from tissues once formed. Remaining 5% derived from connective tissue & include serum amyloid P component, glycosaminoglycans & proteoglycans.

i/ chronic inflammatory process elsewhere in the body (in most cases);

ii/ tumours as in plasma cell & thyroid tumours

iii/ prion disease eg. BSE



What is the difference between primary amyloidosis & secondary amyloidosis?

Give examples of each.

Primary amyloidosis is seen in neoplasia/neoplastic diseases. AL =  amyloid light chain - made up of complete immunoglobulin light chains secreted by plasma-cell tumours. Ie., too much antibody proteins
Eg.,  affected animals have monoclonal gammopathy with abnormal protein in urine (Bence-Jones proteinuria)
- many cases in humans not associated with plasma cell tumours but with increase of normal plasma cells in bone marrow (may produce more immunoglobulin) - sometimes called Dyscrasia

Secondary amyloidosis - amyloid protein deposited in the renal glomeruli of dog & ox - AA = amyloid associated protein
- also called Reactive Systemic Amyloidosis
- secondary to inflammatory reactions, particularly chronic infections


What is renal amyloidosis and what are its effects?

Renal amyloidosis is a secondary amyloidosis, as a reaction secondary to inflammatory reaction esp to chronic infection, as opposed to primary, which is due to neoplastic disease.

Aka Reactive Systemic Amyloidosis & Nephrotic Syndrome

AA (amyloid-associated) protein deposited in the renal glomeruli of dog & ox. 


- failure of normal renal function, sustained loss of protein (mainly albumin) into urine
- reduces osmotic potential of blood to attract fluid back into the blood at the venous end of the capillary bed
- results in oedema of the subcutis and abdominal cavity


What are three types of secondary amyloidosis that can effect the body's organs as a result of a inflammatory reaction to a chronic infection? 

Renal amyloidosis - aka Nephrotic Syndrome or Reactive Systemic Amyloidosis; amyloid deposition in renal glomeruli

Hepatic amyloidosis - Amyloid deposition in the liver causes hepatomegaly with a high risk of haemorrhage

Endocrine amyloidosis - Amyloid deposition can occur in endocrine organs (e.g. the islets of Langerhans in the pancreas)


What is infiltration in terms of pathology?

When something accumulates in the individual cell or surrounding tissue:

1. Glycogen

2. Viral inclusion bodies

3. Abnormal storage products


What is necrosis? 

Death of substantial numbers of cells within the living body, or attached to the living body, resulting in either:

a/ further changes in tissue itself and/or

b/ surrounding unaffected living tissue reacting against necrotic tissue.


What are the causes of necrosis?

Ischaemia / Infarction

Non-living agents: Physical injury, Chemical injury

Living agents: bacteria, parasites, viruses



What is ischaemia and how does it lead to necrosis? 

Ischaemia is reduced blood supply to tissue. 

It can lead to necrosis (ischaemic necrosis) if blood supply is severely reduced due to:




of blood vessel


Give examples of how COMPRESSION of a blood vessel can lead to ischaemic necrosis.

1. Intestinal torsion
2. Intestinal intussusception (portion of sm. intestine becomes enveloped in another)


Venous flow impeded
Organ swells due to congestion
Swelling impedes arterial flow
Arterial flow stops
Tissue undergoes ischaemic necrosis
Intestinal blood barrier compromised - ie., breakdown of villus structure in lining
Bacterial toxins absorbed; prone to rupture with peritonitis ∴
Toxaemia & death


Give examples of how NARROWING of blood vessel can lead to ischaemic necrosis.

1. Arteriosclerosis - vessel wall becomes thickened, not due to any deposition of material; may occur in hypertension, age-related

2. Atheriosclerosis - deposition of lipid, cholesterol & inflammatory macrophages can cause thickening & narrowing of arteries & ischaemia; rare in animals, occasionally dogs with hyperthyroidism


Give examples of how BLOCKAGE of a blood vessels can lead to ischaemic necrosis.

1. Thombosis - Aortic thrombus in cat with hyperthyroidism; embolism

2. Valvular endocarditis (bacterial infection of valve leaflets)

3. Erysipeloxthrix rhusiopathiae in pigs (diamond-skin disease) - Bacterial infection of skin, occlusion of vessels supplying skin, which becomes ischaemic

4. Ingestion of ergot (fungus) - Ischaemic necrosis of extremities, especially ears, digits. Can cause abortion due to ischaemia of placenta.


Give an example of how an infarction can lead to necrosis?

Acute renal infarct - arterial vascular event -- sudden drop in blood supply -- that may cause irreversible damage to kidney tissues. It is often a sign of systemic illness.

Renal infarction can result from an embolus arising in a distant location or from thrombosis of the renal artery. Renal artery thrombosis can be secondary to a diseased artery, systemic hypercoagulability or trauma. Treatment of renal infarction will usually begin with anticoagulation. 


What are some examples of physical injuries that can lead to ischaemic necrosis?

- Burns
- Cold
- Frostbite
- X-rays
- Pressure - eg., recumbent horses can develop ischaemia due to weight of organs pressing down on back & hindlimbs
- Pinching or crushing of tissue - eg. Burdizzo castration


What are some examples of chemical injuries that can lead to ischaemic necrosis?

Oak poisoning (tannins) of foal


Give an example of how living agents -- bacteria, fungi, parasites, viruses -- can cause ischaemic necrosis?

Black Disease 

 aka Infectious Necrotic Hepatitis

A sheep infected with Fasciola hepatica trematode(liver fluke) suffers liver-parenchyma necrosis as the parasite triple in size, blocking blood supply to the liver.  The liver is haemhorragic & necrotic.

The necrotic, anaerobic/hypoxic conditions enable secondary infection by Clostridium novyii Type B, the spore-forming Gram (+) bacillus bacteria that produces toxins.


What are the three zones of necrosis, when microscopically observed, in histological sample?

1/ Sphere of necrosis - where the effect of the causal agent is maximal
2/ Zone of degeneration - a little further away, where the tissue will be damaged but not yet dead
3/ Zone of inflammation - still further away, where effect of agent is insufficient to cause death or degeneration of cells


What are the cellular events of necrosis that can be observed microscopically?

1/ Pyknosis 
2/ Karyorrhexis
3/ Karyolysis 
4/ Cytoplasm sometimes stains brighter pink (more eosinophilic due to lower pH)


What is pyknosis? 

It's a cellular event in necrosis that can be seen histologically: chromatin condenses & becomes small, dark & shrunken



What is karyorrhexis?

It's a cellular event in necrosis that is more advanced than pyknosis. Histologically, the nucleus can be seen to have broken up into several dense pieces.


What is karyolysis?

It's a cellular event in necrosis that is more advanced than pyknosis and karyorrhexis.

It's dissolution of the cell's nucleus. Staining of nucleus with haematoxylin becomes faint & only ghost outline remains.


What happens to the colour of cytoplasm in a cell that is undergoing necrosis when viewed with hematoxalin stain?

It stains brighter pink ie., more eosinophilic due to lower pH. 

(Eosinophilic is more acidic = pink

Basophilic is more basic/alkaline = blue)


What are the five different types of necrosis?

1. Coagulative

2. Liquefactive - Malacia (CNS)

3. Liquefactive - Abscesses

4. Caseous

5. Fat


What causes coagulative necrosis & what does it look like?

CAUSES: Bacteria that produce toxins esp. Clostridium spp; Infarction; some foci of viral replication eg. Canine herpesvirus-1

GROSS: Remains firm; drier on cut surface but still resembles in outline the adjacent viable tissue

MICRO: General architecture preserved. Cells may appear slightly larger & outline lost. Cytoplasm appears structureless & homogenous. Important nuclear changes (pyknosis, karyorrhexism karyolysis); might see inclusion bodies



What are the differences between liquefactive necrosis involving CNS malacia & liquefactive necrosis involving abscesses?

They affect different tissues and look different grossly & microscopically.

1. Liquefactive necrosis involving malacia of CNS tissue:

GROSS: Gaps apparent in white matter of brain and spinal cord

MICRO: Vacuoles appear where grey matter of brain is becoming necrotic

CAUSES: Thiamine (Vit. B) deficiency in cereborcortical necrosis in ruminants
Lead toxicity in ruminants
Salt poisoning in pigs

2. Liquefactive necrosis involving abscesses: 

GROSS: Whitish, yellowish watery or clumpy pus

MICRO: Necrotic area composed of: varying stages of degeneration & death of neutrophils; homogenous structureless mixture of remnants staining faintly bluish

Pyogenic membrane - reddish membrane on inner surface of capsule composed of blood vessels responsible for transporting the vast # of neutrophils to lesion

Fibrous tissue capsule- part of host inflammatory response walls off the irritant

CAUSES: Pyogenic (pus-producing) organisms.

Pus = dead & dying neutrophils, dead tissue & organisms causing necrosis
Bacteria cause necrosis & attract vast #s of neutrophils ➔ neutrophils kill ➔ dying neutrophils release proteolytic enzymes ➔ digest necrotic tissue ➔ kill further tissue cells ➔ kill other incoming neutrophils


What is caseous necrosis? What does it look like and what causes it?

CAUSE: Mixture of coagulation & liquefactive necrosis

Specific organisms eg. Mycobacterium tuberculosis can cause granulomas; fungi, parasites & foreign bodies also cause granulomas

GROSS: - “Cottage-cheese”-like; white/grey/yellowish; consistency varies according to fluid content; some dry & crumbling

MICRO: Complete loss of cell architecture. Purplish necrotic material due to:

- random intermixing of nuclear & cytoplasmic components that stain with H&E
- lots of MACROPHAGES in granulomas: large proportion of necrotic tissue is composed of macrophages recruited into tissue to engulf organism
- can see multinucleate giant cells: merger of macrophages in histo sample of M. tuberculosis-infected tissue; Mycobacteria have fatty cell wall that resists digestion & other factors, allowing replication within macrophage & evasion of phagolysis ➔ organisms burst macrophage ➔ engulfed by other macrophages



What is fat necrosis? What does it look like & what causes it?

Adipocytes die ➔ fat broken down into fatty acids ➔ these combine with Ca++, Na+ & K+ to form soaps (saponification) ➔ soaps provoke inflammatory response ➔ do not dissolve but remain indefinitely & often calcify

GROSS: Areas of focal opacity, very hard consistency

MICRO: Vacuoles surround inflammation


Enzymatic - release of pancreatic enzymes esp lipase from damaged pancreas into adjacent mesenteric fat eg., pancreatitis

Traumatic - in subcutaneous tissue following trauma to area; quite common in brisket of recumbent animals due to prolonged pressure

Diet-related - rarely in cats with antioxidant-deficient diets eg., Vit. E, eating only fish.


What is gangrene? 

Post-necrotic change
- degradation of dead tissue AFTER necrosis

- it is NOT necrosis


What are the two types of gangrene?

Wet: Life-threatening; Eg., common in bovine mastitis due to S. aureus (primary)

Primary - agent that initially kills tissue also putrefies it Live skin rotting, malodourous

Secondary -  dead tissue invaded by organisms that putrefy ittissue already dead/necrotic, black, pus-y, rotten, starting to putrefy


Dry: Like mummification Eg., Post-septicaemic salmonellosis; appears leathery, dessicated then sloughs off; occurs on extremities; air passing over extremities removes fluid content of dead tissue; appears leathery


What is apoptosis?

Programmed death of scattered single cells in living tissues


Eg., mammary gland after lactation, endometrial cells during menstruation, death of lymphocytes in tolerance, low levels of injurious substances, some viruses & tumours, extra cells produced in embryogenesis

GROSS: No reaction, no inflammation

MICRO: Cell membrane intact



What is the difference between hyperaemia & congestion?

Hyperaemia: Engorgement of the vascular bed due to ↑ INFLOW of blood. There is more blood in circulation/in blood vessels because there is more physiological demand for blood flow.

Eg., from muscles during exercise, loss of heat from skin or digestion of food. Hyperaemia can also be the earliest response in inflammation (eg., swelling).

Congestion: Engorgement of vascular bed due to ↓ OUTFLOW of blood. There is more blood clogging up the veins because it can’t flow out from one end to the other. It can lead to hypoxia or cyanosis, since oxygenated blood doesn’t make it through the circulation, the stagnant blood loses its oxygen.

Eg., local obstruction or congestive heart failure. 


What is venous congestion?  What are some examples of chronic & acute venous congestion?

Venous Congestion - ↓ flow of blood to tissues caused by functional or structural blockage to blood flow.

Chronic - congestive heart failure - buildup of blockage
Acute - acute heart failure - sudden blockage (lung & abdominal viscera don’t get enough blood); spleen after barbiturate euthanasia; accidental compression of  tissues eg., abdominal twist
Can be localised to an organ or generalised, affecting the whole body.


Intestinal torsion is a cause of localised venous congestion. What happens?

Compression of the vessels occludes the thin-walled veins, stopping blood from leaving the tissue

For a time blood can still enter tissue, passing through the muscular arteries

Dark red venous blood collects in capillaries and veins

Organ may become red/black and if the condition persists anoxic necrosis will occur 


Congestive heart failure, often with oedema, is a cause of generalised venous congestion. What happens?

Obstruction of blood flow through the heart

Blood is held back or “pools” behind the point of obstruction in the circulation

Left-sided heart failure - due to congestion of pulmonary (lung) circulation
Right-sided heart failure - due to congestion of hepatic (liver) circulation


List causes of congestive heart failure that can lead to generalised venous congestion.

Damage to heart valves - eg., endocardiosis (congenital in King Charles Cavaliers), endocarditis (bacterial)

Changes to heart muscle - cardiomyopathy

Compression of heart from outside - eg. wire, hydropericardium

Neoplasia affecting heart


What's the difference between pathological congestion & hypostatic congestion?

Hypostatic congestion occurs after death: Before blood clots, it pools due to gravity to lowest parts of organ/body; important to distinguish from pathological congestion, which occurs during life to cause or as a symptom of disease.


What is oedema?

Abnormal accumulation of fluid in INTERSTITIAL TISSUES or BODY CAVITIES. It occurs when there is an imbalance in the forces that retain blood/fluid in the blood vessels and those that retain fluid in the interstitial spaces & body cavities.


What are the two types of oedema fluid?

1/ Exudate - protein-rich, containing many inflammatory cells, produced during inflammatory oedema

    2/ Transudate - low in protein & cells, clear-running, produced during non-inflammatory aka haemodynamic oedema


What are the four main causes of oedema?

1. ↑ Capillary Blood Pressure aka Hydrostatic Pressure

 2. Plasma Osmotic Pressure - loss or lack of blood protein (mainly albumin)

3. ↑ Capillary Permeability - usually inflammatory in origin

4. Blockage of Lymphatic Flow - cells, including tumour cells


↑ Capillary Blood Pressure aka Hydrostatic Pressure is a cause of oedema. What is the mechanism & give examples.

Increase in blood pressure prevents adequate resorption of fluid at venous end of the capillary bed.
Blood can’t flow out of the veins, so pressure increases in the capillary bed, forcing fluid out into the interstitial space between cells.


Localised - occlusion of veins:
Venous congestion: Intestinal torsion, heart-valve disease, cardiomyopathy, left-sided or right-sided heart failure

Generalised - cardiac failure:
- Ventral subcutaneous oedema - seen in heart failure in horses & cattle
- Anasarca - generalised tissue oedema most noticeable in subcutaneous tissues


Plasma Osmotic Pressure - loss or lack of blood protein (mainly albumin) - is a cause of oedema. What is the mechanism & what are some examples?

Osmotic (oncotic) pressure is the force responsible for pulling tissue fluid BACK INTO BLOOD VESSELS at venous end; it’s the protein gradient where water goes from low-protein concentration to area of high-protein concentration.

Reduction in albumin due to malnutrition, loss or reduction in formation by liver or protein-losing pathologies means proteins can’t be absorbed across tissues into blood vessels, so fluid flows OUT of blood, where protein is low, into tissue or body cavities where there is higher protein levels.


Protein-losing enteropathy - loss of protein due to chronic inflammation of GIT; animal can’t absorb protein via GIT or it passes in faeces. Water leaves blood vessels (area of low protein) into GIT tissue.
Haemonchus contortus - blood-sucking nematode in sheep abomasum leading to “bottle jaw”


Protein-losing nephropathy aka Nephrotic Syndrome - subcutaneous oedema as fluid accumulates in body cavities because proteins are lost via urine in cases of glomerulonephritis & amyloidosis
Ascites - excessive fluid in abdominal cavity, common in dogs
Hydrothorax - excessive fluid in thorax, common in cats.

Chronic liver disease - may interfere with albumin synthesis
Liver fluke (Fasciola hepatica) -  in sheep
Fibrosis of liver - in dogs


↑ Capillary Permeability - usually inflammatory in origin - is a cause of oedema. What is the mechanism & what are some causes of this response?

Increased capillary permeability allows escape of plasma protein into interstitial fluid & thereby ↑ osmotic pressure

Fluid then is drawn INTO the interstitial fluid FROM the plasma.

Systemic causes:
Bacterial toxins
Various chemicals
Some immune-mediated conditions - Feline Infectious Peritonitis (FIP)

Local causes:
Inflammation - vasoactive substances eg., histamine, substance P, ↑vascular permeability so fluid & inflammatory cells move out of vessels into extracellular tissue, forming cell-rich exudate



Blockage of Lymphatic Flow - by cells, including tumour cells - is a cause of oedema. What is the mechanism & what are some examples?

Blockage of lymphatic flow refers to an obstruction from inside or outside the blood vessels, or removal of lymphatics. Lymphatics help maintain interstitial fluid at normal homeostatic volume by draining waste out of blood, produces localised oedema

Can be caused by trauma, surgery, inflammation or neoplasia.


Cells of malignant epithelial tumours (metastases) travel through lymphatic system to seed other tissues & may cause obstruction
Breast cancer


What is haemhorrage & how does it differ from congestion?

Haemorrhage is the escape of blood from vessels. Distinguished from congestion because the blood is OUTSIDE of vessels as opposed to inside.


In terms of haemhorrage, what is rhexis & what can cause it?

Rhexis is a type of haemhorrhage due to physical rupture of a blood-vessel wall.


- Trauma
- Haemorrhagic enteritis
- Erosion of blood vessels by tumours or absesses
- Idiopathic rupture of arteries 




What are some examples of rhexis (rupture of blood-vessel wall)?

Intrapericardial rupture of aorta in horse
Arterial rupture in pigs associated with Cu deficiency
Adult turkeys often have rupture of various arteries


What do


have in common?

They are all types of haemhorrage into body cavities caused by rhexis (physical rupture of blood-vessel wall).


What are the similarities & differences between a haematoma & a bruise?

Both are haemhorrages within tissue due to rhexis.

Haematoma: release of blood into tissue forming clot; can be associated with angiogenic tumours

Bruise: red for 48 hrs, then turns yellow due to macrophages converting haemoglobin to haemosiderin (not as serious)


What do

Gastric haemorrhage

have in common?

They are all forms of loss of blood (haemhorrage) from the body, due to rhexis (rupture of blood vessel). 


What is epistaxis? 

Nosebleed; originates anywhere in respiratory system; can occur in lungs after heavy exercise or in problem with gutteral pouch in horses. 


Example of haemhorrage out of the body.


What is gastric haemhorrage?

Gastric secretion turns blood dark brown, “coffee-ground” appearance; called haematomesis when vomited up & melena when passed in faeces (blood originated in stomach/upper SI, often due to ulceration)

Example of haemorrhage OUT of the body due to rhexis.


What is dysentery?

Blood in faeces when bleeding is low down in the GIT & when blood is passed in faeces relatively unchanged.

Example of haemhorrage OUT of the body due to rhexis.


What is haematuria?

Blood in urine; loss of whole blood.

Distinguish from haemoglobinuria (loss of haemoglobin into bladder following intravascular haemolysis). 

Example of haemhorrage OUT of the body due to rhexis. 



What is haemoglobinuria?

Loss of haemoglobin into bladder following intravascular haemolysis. 

Distinguish from haematuria - loss of whole blood.


Example of haemhorrage OUT of the body due to rhexis.


What is diapedesis & how does it differ from rhexis?

Both diapedesis & rhexis are forms of haemorhorrage.

Diapedesis are small losses of blood, usually from tiny ruptures in microvasculature.

Rhexis is bigger, physical rupture that lead to bigger haemorrhages.




What are the different types of diapedesis that can be observed in live tissue?

Usually seen on skin, mucous membranes & serosal surfaces:

Petechiae - minute, pinpoint

Ecchymoses - 1-3 cm diameter & blotchy

Purpura - mix 


What are some causes of diapedesis in animals?

Purpura haemorrhagica - in horses after an infection, esp. strangles. Endothelial damage caused by accumulation of immune complexes.

Haemophilia - rare but reported in dogs & pigs; failure of normal blood clotting of blood due to absence of clotting factors

Dicoumeral poisoning - warfarin, an antagonist to Vit. K, or prolonged feeding of sweet clover

Astrongylus vasorum - worm that parasitises pulmonary artery, right ventricle & lungs of dogs & foxes; secretes anticoagulant causing sporadic haemorrhage


Describe the mechanisms by which vascular collapse and shock occur.

Shock comes about when the entire body suffers a severe lack of blood flow, or hypoperfusion. This is due either to decreased effective circulating blood volume, in the case of haemorrhage, thromboembolism or heart failure, and/or increased peripheral vascular resistance (ie., higher blood pressure), which reduces blood flow to tissues.

Shock can also occur with hypotension, or very reduced blood pressure, which can result in impaired blood flow, hypoxia and a shift to anaerobic metabolism of cells, cellular degeneration and apoptosis.

It is a common final outcome for severe haemorrhage, dehydration, severe trauma, burns, major myocardial infarction, massive pulmonary embolism & sepsis. 


What are the three categories of shock?



Maldistribution of blood


What is hypovolaemic shock & what causes it?

Reduced circulating blood volume; loss of 10% blood volume can occur without causing a fall in blood pressure. When loss of more than 35% blood volume occurs, BP falls dramatically & tissue perfusion cannot be maintained
- 80-90% young, healthy animals survive




What is cardiogenic shock & what are the causes?

Heart fails to pump enough blood or fails to do so forcefully enough to perfuse the systemic circulation. Unsuccessful compensation by sympathetic stimulation results in stagnation of blood & progressive tissue hypoperfusion


Myocardial infarction
Cardiac arrythmias
Obstruction of blood flow from the heart (pulmonary embolism)
Cardiac dysfunctions


What is blood maldistribution shock and what are the causes?

Decrease in vascular resistance (ie., increase in systemic vasodilation) resulting in relatively reduced perfusion to vital organs. Peripheral blood-pooling & stagnation.


Septic - most common & important; infectious organisms (eg. bacterial endotoxin) induce excess release of vascular & inflammatory mediators (eg. DIC) → multi-organ failure

Anaphylactic - generalised hypersensitivity reaction, eg., plant allergens, drugs, vaccines (IgE on mast cells →histamine → vasodilation →vascular permeability)

Neurogenic - induced by trauma, electrocution, fear, emotional stress (profound autonomic stimulation → widespread vasodilation)



Describe how blood clots.

Blood-clotting, or haemostasis, begins with vasoconstriction of the ruptured blood vessel. This is caused by myogenic spasm (contraction of the vascular muscle cells initiated by themselves), production of vasoconstrictor thromboxane by platelet enzymes and nervous stimulation by pain sensation. This is followed by primary & secondary clotting, then fibrolysis

Primary clotting involves the adhesion, activation and aggregation of platelets to the site of rupture. When the blood is exposed to collagen in the ruptured vessel, platelets change shape and begin secreting factors that cause them to adhere to the ruptured vessel’s endothelial cells, which normally prevent such sticking of platelets. Platelets especially adhere to Von Willebrand Factor, which leaks into the tissues from the plasma.

Activation occurs when the irregularly shaped, contracting platelets secrete factors such as ADP  and 5-HT (seratonin, a vasoconstrictor), while the phospholipid in the platelets’ cell membrane generate arachidonic acid, which acts as a substrate for the enzyme cyclooxygenase (COX). COX, reacting with the platelets’ arachidonic acid, catalyses synthesis of TxA2, aka thromboxane,  another vasoconstrictor. Together, ADP and thromboxane activate nearby platelets.

The aggregating platelets express GP IIb/IIIa surface receptors, which bind soluble fibrinogen in a cross-link pattern, forming a temporary platelet plug.

Secondary clotting occurs via the coagulation cascade. This can be triggered extrinsically when the vessel wall is ruptured, and intrinsically, when there’s trauma to the blood or exposure to collagen.  The first step in the extrinsic pathway is the release of tissue factors (TF) from the nearby tissue. These factors are made of lipoproteins and phospholipids especially that act like proteolytic enzymes and activate many of the clotting factors. A key factor is the conversion of Factor X to Factor Xa, which sets in motion the interaction of prothrombin activator in the presence of Ca++ to convert prothrombin, which is already in the blood, to thrombin. Thrombin then converts soluble fibrinogen into insoluble fibrin fibres, forming a haemostatic clot. This is a rapid process that protects the body.

The intrinsic pathway starts by the activation of Factor XII (Hageman) to Factor XIIa, and there is no interaction with the TF of the extrinsic pathway. The common final pathway they share begins with the conversion of Factor X to Factor Xa, after which prothrombin + Ca++ converts prothrombin to thrombin, etc. This is a slow process that occurs outside of the body, eg., in a test tube.

Finally, the clot undergoes fibrinolysis. The tissue around the clot and the underlying endothelial cells release tPA, aka tissue plasminogen activator, which converts plasminogen already in the blood to plasmin, which digests the fibrin until it disappears. Plasmin also digests key clotting factors, including prothrombin.



Give examples of how the body can fail to clot.

A failure to clot, or dyscrasia, can mean the body lacks or has defective clotting factors, as in the case of haemophilia.

It can also be due to liver disease, which cuts down on the production of prothrombin, fibrinogen and other clotting factors.

A deficiency of Vitamin K can also lead to dyscrasia, and it can occur with the ingestion of warfarin, which blocks Vit. K, or sweet clover, which has a similar effect.

Angiostrongylus vasorum secretes an anticoagulant into the blood.

Thrombocytopaenia is a condition in which there is a decrease in platelets due to infection, drugs, bone-marrow tumours or poisons.

Septicaemia can lead to widespread damage to the vascular endothelium. 


Discuss how pathological clotting of blood occurs & its causes.  



Pathological clotting means clotting that occurs when it’s not supposed to. This is called THROMBOSIS.

It is typically due to three primary influences (Virchow’s Triad):

i/ Endothelial injury - this also triggers the normal clotting cascade, due to all the same things that can cause normal clotting, as well as depletion of plasminogen activator inhibitors. Remember that tissue plasminogen activator tPA sets in motion fibrinolysis so a tPAI, or PAI, would inhibit fibrinolysis, resulting in a clot not dissolving.

ii/ Alteration of blood flow - stasis (usually venous) or turbulence (usually arterial) caused by intestinal torsion, external compression of vessel or cardiac disease causing a blockage.

iii/ Hyper-coagulability of blood - could be due to ↑ number of platelets (diabetes mellitus, cancer, heartworm, uraemia, nephrotic syndrome) , ↑ in clotting fibres and fibrin (nephrotic syndrome, DIC, neoplasia), ↓ in fibrinolytic system, metabolic abnormalities (eg. hyperadrenocorticism).


How do cardiac thrombi differ in appearance & location from venous thrombi?

Arterial/Cardiac Thrombi:

Usually non-occlusive (result of rapid & high vol flow; turbulence)

Smaller arterial thrombi may be occlusive

All begin at sites of endothelial injury or turbulence

Grey-red, laminated layers (platelets + fibrin and RBCs)

Major sites: left ventricle, faulty heart valves, sometimes in peripheral circulation

Venous Thrombi:


Occur in sites of stasis

Long red-blue cast of lumen

Enmeshed RBCs + fibrin - red-blue MESH instead of thrombus

Major sites: veins of distal limbs (DVT - deep vein thrombosis)




What is thrombosis? How is it related to an embolism aka thromboembolism?

A thrombosis is an inappropriate clot.

A thromboembolism is a fragment of a thrombus (clot) that breaks away and flows through the blood stream and ends up blocking a blood vessel. The vascular occlusion can be complete or partial, and can lead to ischaemia & necrosis. 


What are the different types of emboli or thromboemboli?

Venous emboli (ie., found in veins) tend to lodge in the pulmonary circulation (ie., pulmonary veins coming back from the lungs). These are called pulmonary infarcts, or right-sided heart failure because the emboli tend to lodge in the vessels leaving the heart to the lungs, ie., pulmonary artery.
Arterial emboli tend to lodge in smaller downstream arteries, often near a bifurcation site, such as at the iliac arteries that branch off the aorta.
Left-sided cardiac emboli are basically arterial emboli, and are often saddle emboli like the emboli of the iliac arteries.


What is infarction?

Infarction occurs when blood supply to tissues is so impaired (ischaemia) that it leads to necrosis of the tissue. The ischaemia can be caused by a thrombosis, emboli, compression from outside the vessel like a tumour, vasoconstriction or vasculitis (inflammatory destruction of blood vessels). The effects in tissue might be reversible, depending on the duration of the ischaemic period or the metabolic demands of the tissue.


Where is infarction likely to be found in the body?

Infarction affects, most importantly, the following end-arteries aka terminal arteries:

renal artery & its branches
splenic artery & its branches
coronary arteries (heart)
some cerebral & spinal-cord arteries
anterior mesenteric artery & its branches


The organs most sensitive to infarction are those that have an “end-artery” structure & are thus very sensitive to hypoxia (ie. organs whose tissue only receives oxygenated blood from one artery, therefore a blockage would cut off all oxygen to that organ): Brain, Kidney, Heart cells


Lung, liver, muscle and intestines are less sensitive because they have alternative blood supplies.


What is an infarct?

An area of ischaemic necrosis. It is usually arterial & not venous.


What is a global infarct?

Large or more proximal artery blockage that causes more severe or extensive infarction, eg. to the whole kidney or the whole lung. 


DIC - Disseminated Intravascular Coagulation - widespread intravascular coagulation/clot, especially microthrombi in the capillaries, caused by widespread generation of thrombin (complication of diffuse thrombin activation, diffuse activation of extrinsic coagulation). 


What is DIC?

Disseminated Intravascular Coagulation

 Widespread intravascular coagulation/clot, especially microthrombi in the capillaries, caused by widespread generation of thrombin (complication of diffuse thrombin activation, diffuse activation of extrinsic coagulation). Generation of TF by endothelial cells in response to bacteraemia, toxaemia, other stimuli or systemic infections that activate widespread release of inflammatory mediators.
Concurrently, high levels of thrombin stimulate various anti-coagulant functions, so fibrinolysis goes into overdrive, while platelets and clotting factors get used up, so paradoxically the body bleeds in widespread haemorrhagic diathesis. Clinically this presents as shock, acute respiratory distres, heart failure and renal failure.


What is the aetiology & pathogenesis of hyaline degeneration in muscle? 

Hyaline degeneration is a segmental (affects a portion but not all) necrosis of the muscle fibres.


Vitamin E and/or Selenium deficiency: both these substances protect cellular membranes from the effects of radicals produced during normal cellular metabolism


What is the expression of hyaline degeneration in a herd of cattle?

Subclinical ill-thrift. Vitamin E and Selenium protect all cells, so the immune system cells are also reduced in their ability to counteract infections.


What is a common cause of Nephrotic Syndrome, or deposit of amyloids in the renal glomeruli, which presents with oedema in the ventral abdomen?

Protein-losing nephropathy aka Nephrotic Syndrome - subcutaneous oedema as fluid accumulates in body cavities because proteins are lost via urine in cases of glomerulonephritis & amyloidosis

Caused by chronic, sometimes purulent (pus producing), inflammatory process elsewhere in the body.
Following continuous stimulation from the chronic inflammatory process (due to chronic liver disease or a liver-fluke infestation), the liver produces a substance (serum associated amyloid –SAA) that deposits and polymerises into fibrils in the glomeruli. This allows protein to leak into the urine (proteinuria), thereby lowering the plasma protein level (hypoproteinaemia) and resulting in transudation of low-protein fluid into the body cavities and tissue spaces.



What does pneumonia in a cat, caused by secondary infection from Aspergillus spp, look like in histology?

See picture. Note:
a. The circular nature of the lesions due to sporing heads of Aspergillus fungus
b. The nuclear changes in the necrotic area (pyknosis, karyorrhexis, karyolysis)


Remember, Aspergillus spp is a filamentous fungus (mycelium), that causes Aspergillosis:

Some strains of Aspergillosis, which spreads by the fragmentation of its septate mycelium into sporing heads that release spores that we see as blue- green mould, are other examples of mycotoxosis as the spores are easily ingested.

- A. fumigatus, A. nidulans, A. flavus, A. niger
- fungus abundant in hay, straw & grain heated during storage
- produce large numbers of dry light spores that become airborne



What might bring on a lung infection in a cat from Aspergillus spp fungus? 

Immunosuppression caused by primary FIV or FeLV infection.


What is the difference between melanophages & melanocytes in histological sample of a darkly pigmented mass?

The pigment that makes the mass dark is melanin.

Melanophage: round and contains lots of pigment

Melanocyte: also contains melanin but of lesser intensity. Produces the melanin and IS the tumour cell. Varies in size and shape.


Why would an animal found to have a darkly pigmented mass on its toe also have a cough?

There could be spread (metastasis) of the melanoma tumour to the lungs. Melanomas on the extremities i.e. digits of dogs tend to be malignant and readily metastasise to the lungs. The oral cavity is another predilection site for malignant melanomas in dogs


In post-mortem exam of a dog with biliary-tract obstruction, its liver is yellow from a back-up of bile (post-hepatic jaundice).

What is responsible for the gross yellowing of other tissues throughout the abdomen?

Bilirubin (hyperbilirubinaemia), which is major component of bile
from erythrocyte breakdown.


What is dilation of alveolar capillaries with red blood cells, and what causes it? 


It is part of the acute inflammatory reaction. The vessels actively dilate to bring fluid and inflammatory cells to the damaged tissue.

Bacterial bronchopneumonia results in hyperaemia (parasite enters via the airways).

Cattle and pigs have a well developed interstitium between lung lobules and for the infection to spread from one to the other, it must go back up the airway of the affected lobule and down into the unaffected lobule. This does not apply to lesions produced by bacteria secreting necrotising toxins.



If thrombi form on the left atrioventricular valve of the heart, where will the most obvious effect be seen in the rest of the body?

As pieces of the thrombus break off, they go through the systemic circulation and a usual site for them coming to rest is the renal vessels and blocking them. The kidney has an ‘end artery’ supply and so the tissue whose supplying vessel has been blocked undergoes an ischaemic necrosis (termed infarction).

Decks in BVM2 Class (88):