Chest Pain

Front 1

List the main categories of blood cells, with additional nomenclature and approx relative quantities.

Back 1

Red blood cells, erythrocytes, 4-6 x 10 to the 6 / uL (45% blood volume)
Platelets, thrombocytes, 1.5-4 x 10 to the 5
White blood cells, leukocytes, 4-11 x 10 to the 3 (<1% blood volume)

Front 2

Classify white cell types.

Back 2

Granulocytes and Agranulocytes.
Granulocytes include neutrophils (40-70%), eosinophils (1-6%), basophils (<1%)
Agranulocytes include monocytes (2-6%) and lymphocytes (20-40%)

Front 3

Give the proportions of different types of white cell.

Back 3

Double amount of neutrophils to lymphocytes (60%-30%)
Roughly the same amount of eosinophils and monocytes (2-5%)
Very few basophils (<1%)

Front 4

Classify white cells as either myeloid or lymphoid.

Back 4

Neutrophils, eosinophils, basophils and monocytes are myeloid
Lymphocytes are lymphoid.

Front 5

Describe a red blood cell.

Back 5

Bi concave disc, 7uM in diameter, no nucleus/organelles

Front 6

How long do red blood cells live for?

Back 6

120 days normally.

Front 7

What is a reticulocyte?

Back 7

A juvenile red blood cell, has lost it's nucleus but may contain some remaining organelles.

Front 8

What is the main function of platelets?

Back 8

Haemostasis and clotting (hence thrombocytes)

Front 9

Describe a platelet.

Back 9

2-3uM in diameter, bi-convex disc, normal organelles and granules containing clotting factor 4, serotonin and some chemotaxins for monocytes and neutrophils.

Front 10

How long does a platelet live for and how are they formed?

Back 10

8-10 days. Formed from fragmentation of a megakaryocyte, which grows in bone marrow until it is massive 50-70uM, cytoplasm then demarcated by ER vesicles which then fuse, ejecting the platelets.

Front 11

Which cell type represents over 90% of granulocytes?

Back 11

Neutrophils.

Front 12

Describe a neutrophil.

Back 12

12-14uM diamater. Multi-lobed nucleus (2-5 lobes).
Contains 3 granule types, one lysosomes, one with inflammatory mediators, and one with adhesion proteins.

Front 13

How do neutrophils get energy?

Back 13

Not many organelles, rely on glycolysis for energy.

Front 14

How do neutrophils phagocytose?

Back 14

Primary granules containing lysosomes fuse with ingested micro-organism, killing them with burst of super-oxide/hydrogen peroxide.

Front 15

What is the primary constituent of pus?

Back 15

Neutrophils.

Front 16

Describe an eosinophil.

Back 16

12-17uM in diameter with a bi-lobed nucleus.
Big and oval in shape. Contain enzymes, lysosomes and histaminase.

Front 17

Which white cell is heavily involved in the phagocytosis of parasites?

Back 17

Eosinophils.

Front 18

Describe a basophil.

Back 18

12uM in diameter, bi-lobed nucleus, strongly granulated with heparin, histamine.

Front 19

How are basophils thought to be related to mast cells?

Back 19

Precursor cell. Both have receptors for IgE and are involved in type 1 hypersensitivity.

Front 20

Describe a monocyte.

Back 20

Large, 20uM in diameter. Horseshoe or kidney shaped nucleus. Enter tissues and become macrophages.

Front 21

Describe a typical lymphocyte.

Back 21

Small, 6-9uM, big nucleus leaving just a thin rim of cytoplasm. Divided into B and T cells.

Front 22

What are large lymphocytes?

Back 22

Either activated B-cells on route to becoming plasma cells, or NK cells.

Front 23

How does the site of haemopoiesis change in the neonate?

Back 23

In utero, begins in the yolk sac, then moves to liver and spleen after 5 weeks. Towards the end of the second trimester, moves to bone marrow.

Front 24

Where is erythropoietin synthesised and why?

Back 24

In kidney is response to oxygen shortage.

Front 25

What are the three main types of arteriosclerosis?

Back 25

Atherosclerosis, progessive disease of the intima
Monckeburg's medial sclerosis, a calcification of muscular arteries
Arteriolosclerosis, a thickening of the walls of small arteries and arterioles

Front 26

What are the major predisposing factors for atherosclerosis?

Back 26

Diet, hyperlipidaemias, hypertension, smoking and diabetes

Front 27

What are some minor risk factors for atherosclerosis?

Back 27

Obesity, physical inactivity, male, old, family history, stress, oral contrceptives

Front 28

Describe the 4 stages in the development of an atheromatous plaque.

Back 28

Stage 1 - Lipid found in macrophages of the intima
Stage 2 - Lipid in both macrophages and smooth muscle cells
Stage 3 - Formation of a fibrous plaque
Stage 4 - Complex plaque, fibrous with a lipid core.

Front 29

What causes the initial formation of a plaque?

Back 29

Some kind of endothelial injury, but there are roles for macrophages, inflammatory mediators, smooth muscle cells and thrombosis.

Front 30

What causes endothelial injury?

Back 30

Dysfunction - increased permeability, increased monocyte adhesion and and increased endothelial cell replication. Smoking and high BP increases vascular permeability.

Front 31

Describe the influence of monocytes in atherosclerosis.

Back 31

Monocytes adhesion increased by molecules VCAM-1 and I~CAM-1. Monocytes and macrophages in the intima express a receptor for LDL. They become foam cells as they fill with LDL.

Front 32

What is the most common form of hyperlipidaemia and is it primary or secondary?

Back 32

Hyperlipoproteinaemia - can be primary (e.g. genetic) or secondary (e.g. nephrotic syndrome, alcoholism, hypothyroidism, and diabetes mellitus)

Front 33

What is thrombosis and when is a patient at risk of sudden death?

Back 33

A complication of late-stage atherosclerosis. Fibrin-rich thrombus may contribute to plaque formation and luminal encroachment. If the plaque occludes >70% risk of sudden death is significant.

Front 34

Why might someone with atherosclerosis limp occasionally?

Back 34

Intermittent claudication. A narrowing of the vascular lumen causing loss of blood flow to the extremities, noticeable when walking after sitting down.

Front 35

What is haemostasis?

Back 35

Body process involved in the prevention of haemorrhage after vascular injury.

Front 36

What are the 3 phases of clotting?

Back 36

Initial, amplification and propagation.

Front 37

What natural inhibitors prevent inappropriate clotting and how do they work?

Back 37

Endothelial cell Nitric oxide and prostacyclins (inhibits platelets)
Tissue Factor Pathway Inhibitor (inactivates factor 10 and 7a)
Active Protein C (acts with Protein S to inactivate 5a and 8a)
Antithrombin (activated by heparin, inactivates thrombin, 9a, 10a, 11a, 12a)

Front 38

Describe primary haemostasis.

Back 38

Adhesion, Activation, Aggregation
1. NO and prostacyclins dispersed
Adhesion: Platelet receptor GP1b binds collagen vWF
Activation: Platelet receptor GP6 activates, releasing ADP, 5-HT, Ca2+
Aggregation: ADP on P2Y and GP2/3 and fibrinogen play a role

Front 39

Describe the initiation phase of clotting.

Back 39

Damaged vasculature exposes tissue factor bearing cells (monocytes/fibroblasts).
Tissue factor combines with factor 7, to give 7a.
7a converts 10 to 10a with Ca2+.
10a converts prothrombin (2) to thrombin (2a) with Ca2+
Thrombin (2a) converts fibrinogen to fibrin which forms the clot.

Front 40

Describe the amplification phase of clotting.

Back 40

Thrombin splits vWF and factor 8 to factor 8a
Thrombin also splits factor 5 (from platelet alpha-granules) to 5a
5a and 8a attract more platelets and activate them.

Front 41

Describe the propagation phase.

Back 41

Thrombin also converts 11 to 11a.
11a converts 9 to 9a.
8a (from amplification) and 9a make tenase (10a)
Tenase forms 'prothrombinase' (a combination of 10a and 5a) This is a very effective producer of thrombin

Front 42

Describe the process of clot destruction (fibrinolysis).

Back 42

Thrombomodulin activates protein C.
Active protein C and protein S block 5a and 8a
Active protein C also inhibits the enzyme (PAI-1) which inhibits Tissue Plasminogen Activator (TPA)
Plasminogen is weaved into the structure of any fibrin clot, but is inactive. TPA activates plasminogen but is normally inhibited in clot formation.
Active protein C removes this inhibition, allowing TPA to convert plasminogen to plasmin, which breaks down the fibrin clot.

Front 43

How do antiplatelets work?

Back 43

Antiplatelets e.g. Aspirin, inhibit COX. COX is expressed by activated platelets, creating thromboxane, which attracts fibrinogen and other platelets. Other anti-platelets work on platelet or fibrinogen receptors.

Front 44

How do anticoagulants work?

Back 44

Block an aspect of the clotting cascade.
Heparin activates antithrombin, which inhibits 10a, crucial for the conversion of prothrombin (2) to thrombin (2a).
Warfarin is a vitamin K antagonist, vitamin K reductase is vital for production of factors 2, 7, 9 and 10.

Front 45

How would you test for the right dose of warfarin and heparin?

Back 45

Front 46

Who is predisposed to thrombosis?

Back 46

Virchow's triad:
Vascular damage - causes arterial thrombosis
Stenosis (low flow) - causes venous thrombosis
Hypercoagulability - thrombocytosis and factor V.

Front 47

What is a 'white thrombus'?

Back 47

Arterial, platelet rich, associated with atherosclerosis/MI. Anti-platelet drugs most effective.

Front 48

What is a 'red thrombus'?

Back 48

Fibrin rich, associated with veins/DVT. Anti-clotting most effective.

Front 49

What is haemophilia?

Back 49

Genetic clotting disorder caused by lack of certain clotting factors. Results in prolonged or defective clotting.

Front 50

Why is vitamin K deficiency a risk for inadequate clotting?

Back 50

Vitamin K an essential precursor to factors 7, 9 and 10 synthesised in the liver. Deficiency causes big problems for clotting.

Front 51

In addition to haemophilia and vitamin K deficiency, name three other conditions which affect clotting.

Back 51

Antiphospholipid syndrome, von Willebrand factor deficiency and Factor V Leiden.

Front 52

What is an infarction?

Back 52

An area of ischaemic necrosis produced by occlusion either of arterial supply or venous drainage.

Front 53

Why is venous infarction less common, and where might you see it?

Back 53

Due to greater number of anastamosing veins. Can get a mesenteric occlusion causing an intestinal infarction. Can also occur in torsion of testes.

Front 54

How are infarcts classified (colour/location/type)?

Back 54

Red infarcts occur with venous occlusion, in loose tissues like the lung, or tissues with two blood supplies. They are haemorrhagic.
White infarcts occur with arterial occlusion, in solid tissues like the heart, lung and kidney. They are anaemic.
Septic infarcts contain bacterial contamination, bland infarcts do not.

Front 55

What are the two types of MI?

Back 55

Transmural (most common) and subendocardial.

Front 56

Describe a transmural MI.

Back 56

Necrosis of the full thickness of the ventricular wall, caused by occlusion of a single coronary artery.

Front 57

Describe a subendocardial MI.

Back 57

Necrosis limited to the inner 1/3rd or 1/2 of the ventricular wall, diffuse stenosing, global hypoxia but no plaque or thrombosis.

Front 58

Describe the structural changes following an MI over time.

Back 58

Initially, ultrastructural changes.
After a few hours - tetrazolium dye detects dehydrongenase
4-12 hours and you see the classic signs of necrosis
12-24hours, beginning of gross changes observable by eye (blue hue)
2-3 days, acute inflammation.
5-10 days, macrophages remove necrotic cardiac muscle cells.
2-4 weeks, granulation, then scarring

Front 59

What complications can be seen post MI?

Back 59

Cardiac rupture - Ventricular free wall, tamponade, interventricular septum (causing shunt), papillary muscles (mitral incompetence)
Pericarditis - Fibrinous/fibrinohaemorrhagic (over necrosis)
Mural thrombosis - Due to damaged myocardium (stasis) and endocardium damage
Ventricular aneurysm - Late stage; transmural infarct heals into thin fibrous layer which bulges out due to pressure in systole

Front 60

What sorts of things form emboli?

Back 60

Thrombi which break or fragment
Material from ulcerating plaques
Septic emboli
Tumour fragments
Fat globules
Air emboli
Parenchymal cells (functional parts of organs)

Front 61

Why is DVT a post-operative risk?

Back 61

Form most commonly in legs, due to stasis. Iliac or femoral veins give rise to emboli which can be up to 30cms in length. Block right atrium, pulmonary artery and right ventricle.

Front 62

What is an atheroma?

Back 62

Build up of cholesterol rich plaques causing stenosis of the artery.

Front 63

What symptom might you expect from an atheromatous plaque?

Back 63

Angina, or intermittent claudication.

Front 64

What is angina pectoris?

Back 64

Temporary pain in chest due to imbalance in demand and supply of oxygen.

Front 65

What are the three types of angina?

Back 65

1. Angina of effort (stable angina)
2. Vasospastic angina
3. Unstable angina (similar to an MI)

Front 66

What causes angina of effort?

Back 66

Stenosis of heart vessel which induces ischaemia when demand rises, e.g. in exercise.

Front 67

What are the 5 main types of pharmacological treatment for angina of effort and where do they work?

Back 67

1. B-blockers
2. Ivabradine
3. Nitrates
4. K+ ATP agonist
5. Ca2+ channel blockers

Front 68

What are the two types of beta blockers and how do they help angina of effort?

Back 68

Atenolol - B1 selective
Propanolol - Non-selective
Work by reducing sympathetic stimulation of the heart, lowing heart rate and contractility

Front 69

How does ivabradine help treat angina?

Back 69

Reduces I-funny, or If, which is an electrical current used in the SA node to control heart rate.

Front 70

Describe the cellular mechanism and main sites of action of GTN, route of administration and effect in the treatment of angina.

Back 70

Nitrates relax smooth muscle cells, mostly in veins (lowering CVP, LVEDP and CO) but also in some coronary collaterals (lowering TPR)
GTN is metabolised by Aldehyde Dehydrogenase (ALDH-2) in mitochondria to produce NO
NO stimulates Guanylate Cyclase to produce cGMP
cGMP lowers [Ca2+] reducing contraction of smooth muscle
Administered under the tongue

Front 71

How are nitrites normally administered?

Back 71

Under the tongue or in patches.

Front 72

Name 2 calcium channel blockers, describe how they work and explain how they help in angina.

Back 72

Verapamil, Nifedipine.
Block Ca2+ entry into smooth and cardiac muscle cells.
Main effect in angina is in arteries, reducing TPR
Verapamil also reduces heart force

Front 73

Name a K+ATP channel agonist, and describe how it helps in angina?

Back 73

Nicorandil. Opens a K+ channel in smooth muscle cells, hyperpolarises membranes, causes vasodilation and reduction in TPR

Front 74

How is vasospastic angina treated?

Back 74

With nitrates, Ca2+ channel blockers and K+ channel agonists.

Front 75

How is unstable angina treated?

Back 75

Like an MI.

Front 76

What are statins?

Back 76

Drugs which inhibit HMG-CoA reductase, a liver enzyme responsible for production of LDL. Result is liver has to use circulating LDL from plasma.

Front 77

What two surgical treatments are considered for angina?

Back 77

CABG - Coronary Artery Bypass Graft - essentially using a piece of vein from an arm or leg to replace occluded coronary vessels.
PCI - Per Cutaneous Intervention, essentially a stent.

Front 78

When and why does venous blood thrombose, and what type of treatment is suitable?

Back 78

Usually due to stasis, causes formation of fibrin deposits. Plane flights and atrial fibrillation. Treated with anti-coagulants.

Front 79

What is heparin and how does it work?

Back 79

Antithrombin activator, which inhibits factor 10a, which is essential for converting 2 (prothrombin) to 2a (thrombin)

Front 80

What is warfarin and how does it work?

Back 80

Vitamin K antagonist. Stops synthesis of factors 2, 7 and 10 in liver. Takes 1-3 days for full effect.

Front 81

What is thrombolysis?

Back 81

Administration of fibrinolytic drug which dissolves clots. Used after occlusive strokes and MI.

Front 82

Give examples of some fibrinolytic drugs.

Back 82

Alteplase, reteplase and streptokinase.

Front 83

What is the time window for the administration of thrombolysis?

Back 83

3 hours in ischaemic stroke, but up to 12 hours for MI.

Front 84

Why give an antiplatelet drug?

Back 84

Reduces risk of arterial thrombosis formation.

Front 85

How does aspirin prevent thrombosis?

Back 85

Aspirin irreversibly inhibits COX, stopping synthesis of TXA and PGI by activated platelets. This is irreversible. Your endothelium repairs and makes new COX, but your platelets cannot.

Front 86

What is the current treatment for coronary thrombosis?

Back 86

Chewable aspirin and fibrinolytic drug immediately, or coronary angioplasty.

Front 87

What are the long term goals of post-MI treatment?

Back 87

Lower risk factors - smoking, BP, cholesterol
Exercise - lower BP, less weight to carry around
Reduce thrombosis risk - give aspirin in low dose
Reduce sympathetic heart stimulation - B-blockers

Front 88

Why would you not give nitrates all the time?

Back 88

Tolerance. Patients build up a resistance to their action, related to inhibition of mitochondrial enzymes. Sporadic administration then is most effective.

Front 89

Why would you not use a beta-blocker for vasospastic angina?

Back 89

B-blockers are not vasodilators, so would have no effect.

Front 90

Other than aspirin, list 2 other antiplatelet drugs.

Back 90

P2Y12 receptor antagonists, and GP2b/3a inhibitors

Front 91

CD4+ and CD8+ T-cells are found in atheromatous plaques, what is their role?

Back 91

Role uncertain

Front 92

What are the 4 major effects of atherosclerosis on arteries?

Back 92

Narrowing of lumen causing ischaemia
Prolonged ischaemia leading to infarction
Possible embolism
Weakening of vessel wall, causing aneurysm