Vascular and interstitial disease

Question 1

What is the phenotype of normal blood vessels?

Answer 1

Anticoagulant form

Lining of the vessel wall is kept smooth by anticoagulant molecules on cell surfaces

Question 2

What happens when there is damage to the endothelial layer lining the blood vessels?

Answer 2

Anticoagulant surface is disrupted with platelets, thrombin and complement

Procoagulant phenotype is expressed

Expression of prothrombotic molecules

Question 3

How do endothelial cells change following vessel damage?

Answer 3

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

Question 4

Condition where clot occludes blood vessels leading to the organ distal to the occlusion becoming ischaemic

Answer 4

Thrombotic microangiopathy

Question 5

Why do RBC become damaged in occluded vessels?

Answer 5

RBC try to work their way through a clot and become damaged

Question 6

What are some causes of thrombotic microangiopathy?

Answer 6

Drugs - chemotherapy

Antibodies binding to endothelium following infectious events or autoimmunity

Complement activation

Vessel wall damage

Question 7

What causes vessel wall damage?

Answer 7

Stress force or hypertension

Question 8

What is the coagulation pathway?

Answer 8

Stimulates blood clot formation

Question 9

What is the complement pathway?

Answer 9

Deposition of complement molecules on endothelial surfaces

Question 10

What happens to the balance of coagulation and complement pathways in pathology?

Answer 10

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

Question 11

Which diseases lead to thrombotic microangiopathy?

Answer 11

Scleroderma - deposition of antibdodies on blood vessel wall

Accelerated hypertension

Haemolytic anaemia

Question 12

What are antiphospholipid antibodies?

Answer 12

Abnormal antibodies against phospholipids on blood vessel walls that increase blood clotting

Question 13

How does haemolytic anaemia lead to TMA?

Answer 13

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

Question 14

What is an example of haemolytic anaemia?

Answer 14

Haemolytic uraemic syndrome

Question 15

What is vasculitis?

Answer 15

Blood vessel inflammation due to activation of leukocytes

Leads to damage of endothelial cells

Question 16

What is the pathophysiology of systemic vasculitis?

Answer 16

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

Question 17

Which antibodies are normally associated in systemic vasculitis?

Answer 17

Anti-neutrophil cytoplasm antibodies

Question 18

What is a simple test that can be done to detect proteins present in inflammation?

Answer 18

Dipstick urine test

Question 19

What is tubulointerstitial nephritis characterised by?

Answer 19

Infestation of WBC in tubules

Question 20

Why are the tubules more predisposed to injury than other parts of the nephron?

Answer 20

Filter the urinary filtrate so exposed to antigens present in the kidney

Question 21

What cell types cause damage to the tubules?

Answer 21

Leukocytes, antibodies and complement

Question 22

How do WBC respond to antigens in the tubules?

Answer 22

Stimulate an inflammatory response

Question 23

What are causes of tubulointerstitial nephritis?

Answer 23

Infections

Drugs

Autoimmunity

Unkown - inflammation resolves as quickly as it started

Question 24

Which drugs commonly cause tubulointerstitial nephritis?

Answer 24

NSAIDS

Proton pump inhibitors

Question 25

Which cell is the main WBC in drug-induced TN?

Answer 25

Eosinophils