Things to learn

Question 1

What are the three ways that activate the complement system?

Answer 1

In complement activation, proteolysis of the complement protein C3 is required. C3 can be cleaved by one of 3 pathways

• Classical pathway: antigen binds to an antibody. This activates the C1 protein which sets off a cascade that cleaves C3
• Alternative pathway: triggered by bacterial endotoxin, LPS
• Lectin pathway: Lectin opsonises carbohydrates on microbes, directly activating C1

Question 2

What are the functions of the complement system?

Name the complement proteins involved.

Answer 2

Inflammation
• C5a stimulates histamine release from mast cells
• Activates the lipoxygenase pathway in neutrophils and monocytes

Opsonization and phagocytosis
• C3b fixes to microbial cell wall (opsonization) and promotes phagocytosis

Cell lysis
• Membrane attack complex proteins ‘drills’ holes in the microbial membrane

Question 3

Describe side effects of glucosteroids

Answer 3

· Osteoporosis
· Myopathy: GCs can affect muscle tone by direct catabolic effect through activation of GC receptor
· Hyperlipidemia
· Increase glucose production, hyperglycemia
· Gastrointestinal: gastritis, peptic ulceration and gastrointestinal hemorrhage.

Question 4

List some glucosteroids

Answer 4

· Cortisone 
· Hydrocortisone 
· Dexamethasone
· Prednisolone 
· Prednisone 
· Triamcinolone
(end in one)

Question 5

Detail how the mevalonate pathway works.

Answer 5

The mevalonate pathway leads to the formation of prenylated proteins and cholesterol.

The pathway starts when two acetyl CoA molecules join together to form “Acetoacteyl- CoA”.

Then, “Acetoacteyl- CoA” gets into a reaction with acetyl- CoA to form HMG - CoA.

HMG - CoA then gets into a reaction with HMG- reductase to form MEVALONATE.

MEVALONATE goes into a series of many reactions to eventually form two important things:

• Isopentenyl pyrophosphate
• Dimethylallyl pyrophosphate

Isopentenyl pyrophosphate + Dimethylallyl pyrophosphate = Geranyl transferase. This is catalysed by PRENYLTRANSFERASE.

PRENYLTRANSFERASE transforms geranyl transferase into Farnesyl transferase = prenylated proteins.

NBP’s block the function of prenyltransferase

Question 6

Describe the pathogenesis of atherosclerosis

Answer 6

· A deficiency in NO production leads to excess constriction of blood vessels and activates of platelets = blood clotting. It increases the stimulation of inflammation and thus vessel permeability

· Endothelial dysfunction: when LDLs are high, they can go through the endothelium and deposit in the tunica intima

· These LDLs are oxidised. Oxidised LDLs activates endothelial cells which causes them to express receptors that attract WBCs

· WBC’s (monocytes and T cells) can move into tunica intima via diapedesis

· Monocytes mature into macrophages which phagocytose the LDLs. They then become foam cells

· Foam cells cause the migration and proliferation of smooth muscle cells from tunica media into tunica intima. This increases the synthesis of collagen = hardening of plaque

· Meanwhile, foam cells die releasing their lipid content. This causes the plaque to grow. As it grows, it can eventually cause rupturing of the endothelium

· To fix the rupture, thrombosis occurs. This forms a huge clot that can impeded blood flow

Question 7

What does the pT measure?

Answer 7

Measures extrinsic pathway (short)

• Factors 2, 5, 10
• Factor 7
• Fibrinogen

Question 8

What does the pTT measure?

Answer 8

Measures intrinsic pathway (long).

• Factors 2, 5, 10
• Factors 8, 9, 11 or 12

Question 9

• Prolonged PT

* Normal PTT/ INR

Answer 9

• Low Vit K
• Defective factor 7
• Warfarin therapy

Question 10

• Normal PT

* Prolonged PTT

Answer 10

• Defective factor 8, 9, 11, or 12

* VwF disease

Question 11

• Prolonged PT

* Prolonged PTT

Answer 11

• Defective factor 2, 5 or 10
• Severe liver disease
• Warfarin overdose

Question 12

When is prophylaxis recommended?

Answer 12

• Prosthetic valves
• History of IE
• Congenital heart disease if only involve; 6 months after surgery OR CHD repair with residual defects
• Cardiac transplantation with the subsequent development of cardiac valvularpathy
• History of Rheumatic Heart disease, only indigenous Australians, Maori and Pacific Islander people

Question 13

List dosage recommendations for adults

Answer 13

Amoxicillin:
2 g

Clindamycin:
600 mg

Cephalexin:
2 g

Question 14

List dosage recommendations for children

Answer 14

Amoxicillin:
50 mg

Clindamycin:
15 mg

Cephalexin:
50 mg

Question 15

Which antihypertensive drug is contraindicated in diabetics and asthmatics?

Answer 15

Beta blockers

Question 16

Which antihypertensive drug is contraindicated in anaphylactics and pregnancy?

Answer 16

ACE inhibitors

Question 17

What are side effects of thiazide?

Answer 17

* Gout (uric acid) 
• Hyperglycaemia
• High Ca
• Low K
• Low Mg