Vascular and interstitial disease Flashcards
What is the phenotype of normal blood vessels?
Anticoagulant form
Lining of the vessel wall is kept smooth by anticoagulant molecules on cell surfaces
What happens when there is damage to the endothelial layer lining the blood vessels?
Anticoagulant surface is disrupted with platelets, thrombin and complement
Procoagulant phenotype is expressed
Expression of prothrombotic molecules
How do endothelial cells change following vessel damage?
No longer flat and anticoagulant -> pulled apart, plumper and active
Basement membrane is exposed
Procoagulant surface is formed
Stimulates platelets and procoagulant molecules to stick to the basement membrane
Condition where clot occludes blood vessels leading to the organ distal to the occlusion becoming ischaemic
Thrombotic microangiopathy
Why do RBC become damaged in occluded vessels?
RBC try to work their way through a clot and become damaged
What are some causes of thrombotic microangiopathy?
Drugs - chemotherapy
Antibodies binding to endothelium following infectious events or autoimmunity
Complement activation
Vessel wall damage
What causes vessel wall damage?
Stress force or hypertension
What is the coagulation pathway?
Stimulates blood clot formation
What is the complement pathway?
Deposition of complement molecules on endothelial surfaces
What happens to the balance of coagulation and complement pathways in pathology?
If the regulators of the balance are insufficient in number or have a genetic abnormality
There is over activation of the pathway
Disease follows
Can also lead to formation of antibodies against the complement pathway
Which diseases lead to thrombotic microangiopathy?
Scleroderma - deposition of antibdodies on blood vessel wall
Accelerated hypertension
Haemolytic anaemia
What are antiphospholipid antibodies?
Abnormal antibodies against phospholipids on blood vessel walls that increase blood clotting
How does haemolytic anaemia lead to TMA?
Complement regulatory proteins are abnormal
Complement pathways is therefore always switched on
This means that complement will get stuck to the endothelium
Leads to endothelial damage
What is an example of haemolytic anaemia?
Haemolytic uraemic syndrome
What is vasculitis?
Blood vessel inflammation due to activation of leukocytes
Leads to damage of endothelial cells
What is the pathophysiology of systemic vasculitis?
Inappropriate activation of WBC due to antigen
WBC release cell contents
Causing damage to the capillary wall
This activates more blood cells to be recruited
Capillary loop stops functioning
Less filtration happens at the glomerulus
Leads to glomerulonephritis
Which antibodies are normally associated in systemic vasculitis?
Anti-neutrophil cytoplasm antibodies
What is a simple test that can be done to detect proteins present in inflammation?
Dipstick urine test
What is tubulointerstitial nephritis characterised by?
Infestation of WBC in tubules
Why are the tubules more predisposed to injury than other parts of the nephron?
Filter the urinary filtrate so exposed to antigens present in the kidney
What cell types cause damage to the tubules?
Leukocytes, antibodies and complement
How do WBC respond to antigens in the tubules?
Stimulate an inflammatory response
What are causes of tubulointerstitial nephritis?
Infections
Drugs
Autoimmunity
Unkown - inflammation resolves as quickly as it started
Which drugs commonly cause tubulointerstitial nephritis?
NSAIDS
Proton pump inhibitors
Which cell is the main WBC in drug-induced TN?
Eosinophils
