Disorders of Haemostasis - Embolism, DIC, Shock

Describe bacterial emboli

E.g. bacterial endocarditis —> bacterial embolus in pulmonary & systemic circulation

What is an embolic-metastatic neoplasm?

A neoplasm caused by emboli aggregation at different sites in the systemic circulation (often caused by bacterial emboli).

What does this show?

Parasitic embolism (heartworm disease in heart of dog)

What does this show?

Fat droplet embolism (after pelvic fracture) in lung of dog

What does this show?

Tumour cell embolus within vein

What is disseminated intravascular coagulation (DIC)?

Acute, subacute or chronic thrombo-haemorrhagic disorder occuring as a secondary complication (severe end of disease spectrum)

What occurs with DIC?

1. activation of the coagulation cascade

2. formation of micro-thrombi throughout microcirculation

3. consumption of platelets, fibrin and coagulation factors —> activation of fibrinolysis

Microthrombi cause occlusion of the capillaries throughout the body.

What clinical signs are associated with DIC?

• Tissue hypoxia

• Infarction

• Haemorrhagic disorder (due to consumption coagulopathy)

What are the underlying mechanisms of DIC?

Caused by:

• Release of tissue factor or thromboplastic substances into the circulation

• Widespread endothelial damage (so coagulation cascade activation)

Summarise the pathogenesis of DIC with a flow diagram

DIC pathogenesis

List at least 2 underlying causes of DIC

1. severe systemic infections due to direct endothelial cell injury or via immune complex deposition

2. septic (endotoxic) shock

3. neoplastic diseases

4. extensive trauma or burns

5. following extensive surgery

How do some gram negative bacteria cause DIC?

• Express LPS on cell wall (endotoxin)

• Causes monocytes to increase synthesis and release of tissue factor (also of IL-1 and TNF)

• This causes endothelial cells to increase the expression of tissue factor and decrease expression of thrombomodulin

• Overall cause is activation of the clotting cascade and inhibition of clotting control

How do some gram-positive bacteria cause DIC?

• Bacterial factors (e.g. glycoproteins) cause excessive cytokine prodcution by monocytes

• This causes a systemic inflammatory response → to clotting → DIC

How do some gram-positive bacteria cause shock?

• Neutrophils adhere to endothelial cells (which have bacteria glycoproteins on)

• They release proteases and oxygen radicals to eliminate glycoproteins

• Causes capillary damage & haemorrhage → shock (if sustained)

Describe endothelial alterations in classical swine fever (capillaries vs arteries)

Capillaries —> swelling of endothelial cells, hyalinisation, complete obstruction

Arteries —> thrombosis, necrosis

Describe rabbit haemorrhagic disease

Massive necrosis of hepatocytes, DIC

Describe the pathogenesis of immune-complex mediated DIC

• Immune complex deposition in vessel walls

• Activates compliment system which incidentally damages the endothelial cells

• Causes the activation of the coagulation cascade

What is shock?

Complete cardiovascular collapse (so unable to perfuse the tissues of the body).

What are the broad causes of systemic hypoperfusion?

• Reduced CO

• Reduced effective circulating blood volume

What are the main causes of shock (list at least 2)?

• severe haemorrhage

• microbial sepsis

• extensive trauma or burns

• large infarction

• massive pulmonary embolism

What is the end result of shock?

Hypotension, impaired tissue perfusion, cellular hypoxia

List at least 2 categories of shock and what their cause is

• cardiogenic shock (failure of myocardial pump)

• hypovolaemic shock (loss of blood / plasma volume)

• septic shock (systemic microbial infection; bacteria, fungi)

• neurogenic shock (depression of vasomotor centre)

• anaphylactic shock (generalised IgE-mediated hypersensitivity)

List the stages of shock

1) Non-progressive stage

2) Progressive stage

3) Irreversible stage

4) Death

Summarise the pathogenesis of septic shock

• Animal exposed to endotoxin (e.g. LPS of gram-negative bacteria)

• Stimulates cells of innate immune system to destroy the toxins

• If there is lots of toxin —> damages endothelium of blood vessels (due to activation of acquired immune response)

• Leads to DIC, haemorrhage or reduced cardiac contractility and systemic vasodilation (latter due to cytokine and inflammatory modulators action)

In what condition do fat emboli typically arise?

Long bone fracture

What it the typical morphological pattern of metastatic neoplasia?

Large primary tumour, disseminated smaller tumours in other organs