Question 1. Sketch the anatomy of the coronary vessels.
Question 2. Which ECG leads are best placed to record changes when the lesion is on the (a) diaphragmatic aspect of the heart, (b) antero-septal region? Which arteries are involved?
Question 3. Indicate the time relationships of the arterial pressure wave to the heart sounds, ECG, and left ventricular pressure.
Question 4. Identify the serum lipoproteins and their role in atherosclerosis.
Question 5. Identify, and briefly comment on the functions of, the cells involved in atheroma formation.
Question 6. An obese 45-year-old man who smokes 20 cigarrettes a day is referred to the lipid clinic. Investigations found the following blood plasma results:
BP 160/100 Fasting glucose 7.5mM (3.27.0mM) Triglycerides 3.5 mM (<2mM) Total cholesterol 8.0 mM (<5.5mM) HDL 0.85mM (0.92.2mM)
a) How do you rate this mans cardiovascular risk? Explain your answer. b) What lifestyle changes would you recommend to improve his health? c) Does he have an abnormality of carbohydrate metabolism?
Question 7. Identify the differences between apoptosis and necrosis.
Question 8. How do tPA and streptokinase work?
Question 9. How do nitrates like glyceryl trinitrate work?
Question 10. Name the 2 major classes of cholesterol-lowering drugs and describe the mechanism of action of each.
Question11. Identify steps in problem-solving when counselling in the post-infarct situation.
STOP! DONT TURN THE PAGE UNTIL YOU HAVE WORKED ON THESE QUESTIONS IN MONDAYS PBL TUTORIAL, OR ATTEMPTED WRITTEN ANSWERS YOURSELF. Quiz for Week 15 Answer Guides
Question 1. Sketch the anatomy of the coronary vessels.
Answer should indicate the origin of the coronary arteries above the aortic valve cusps, and the territory of the major vessels and branches. The venous drainage should be identified. Some anomalous drainage going into the left atrium instead of the right contributes to the normal right to left shunt.
Question 2. Which ECG leads are best placed to record changes when the lesion is on the (a) diaphragmatic aspect of the heart, (b) antero-septal region? Which arteries are involved?
(a) II, III and aVF; (b) precordial leads, esp V2 V5; arteries follow on from Question 1
Question 3. Indicate the time relationships of the arterial pressure wave to the heart sounds, ECG, and left ventricular pressure.
This is a good diagram to draw as it encapsulates most of the critical ideas about the cardiac cycle: it is in every physiology book though the wave shapes tend to be artistic rather than realistic.
Question 4. Identify the serum lipoproteins and briefly describe their role in atherosclerosis.
LDL has the highest cholesterol content and transports lipids to the periphery; CVS risks increase with levels. VLDL contains triglyceride; risks increase with levels. HDL is involved in cholesterol transport out of the tissues back to the liver; increased levels reduce risk. Total cholesterol risk increases sharply above about 5.2 mmol/l. Oxidised cholesterol increases with age and disturbs the feedback control loops so that total cholesterol rises progressively from infancy onwards.
Question 5. Identify, and briefly comment on the functions of, the cells involved in atheroma formation.
Endothelial cells: platelet aggregation/thrombus formation, LDL uptake. Platelets: form thrombus. Smooth muscle cells: take up LDL forming foam cells. Macrophages: oxidize LDL and take up lipids. Neutrophils: phagocytosis, secrete proteases and inflammatory mediators causing ongoing damage.
Question 6. An obese 45-year-old man who smokes 20 cigarrettes a day is referred to the lipid clinic. Investigations found the following blood plasma results:
BP 160/100 Fasting glucose 7.5mM (3.27.0mM) Triglycerides 3.5 mM (<2mM) Total cholesterol 8.0 mM (<5.5mM) HDL 0.85mM (0.92.2mM)
a) How do you rate this mans cardiovascular risk? Explain your answer. b) What lifestyle changes would you recommend to improve his health? c) Does he have an abnormality of carbohydrate metabolism?
a) His cardiovascular risk is high on account of his moderately elevated total cholesterol, low HDL, smoking, hypertension and possibly diabetes. b) Weight reduction, low cholesterol diet, smoking cessation and regular mild exercise. c) This level of fasting glucose is consistent with diabetes mellitus. It needs to be confirmed because diagnosis cannot be made on the basis of one measurement.
Question 7. Identify the differences between apoptosis and necrosis.
Apoptosis is programmed cell death, involving activation of a sequence of genes; it is ordered and results in a compacted, dehydrated cell with fragmented chromatin, which is disposed of neatly by phagocytosis by surrounding cells.
Necrosis results from injuries such as ischaemia and occurs when cells cannot maintain basic homeostasis: - such as maintaining ion gradients for osmoregulation (volume regulation) and electrical polarization of the membrane, keeping out calcium, maintaining the pool of glutathione to prevent oxidative damage, etc. It results in inflammation, cellular infiltration, and the repair phase will produce scar tissue.
Question 8. How do tPA and streptokinase work? What are the advantages and disadvantages of each?
Streptokinase is an enzyme which acts by binding to plasminogen. The streptokinase-plasminogen complex then activates other plasminogen molecules by converting them to the active proteolytic enzyme, plasmin, which cleaves fibrin. Because it is derived from beta-haemolytic streptococci, it is cheap but its effectiveness can be reduced in patients who have developed antibodies to it through previous strep infections.
tPA acts by a different mechanism from the endogenous tissue plasminogen activator. It specifically activates only the plasminogen that is within blood clots, thus minimising haemorrhage from general plasminogen activation. However, it is much more expensive than streptokinase.
Question 9. How do nitrates like glyceryl trinitrate work?
Nitrovasodilators reduce total peripheral resistance, reducing arterial blood pressure (afterload), dilating the large veins, reducing venous return (preload) and therefore reducing cardiac workload in two ways. They are NOT coronary vasodilators. They donate oxides of nitrogen including nitric oxide, which is biologically active in minute concentrations. NO is normally produced by vascular endothelial cells and acts as a vasodilator by activation of guanylate cyclase, producing cyclic GMP, which triggers a cascade of phosphorylation reactions leading to relaxation of vascular smooth muscle.
Question 10. Name the 2 major classes of cholesterol-lowering drugs and describe the mechanism of action of each.
i) Statins: Examples are simvastatin and lovastatin. These act by inhibiting HMG-CoA reductase, the rate-limiting enzyme in the hepatic synthesis of cholesterol. In the face of decreased cholesterol levels, the liver up- regulates its LDL receptors, thereby pulling in LDL-cholesterol from the periphery for use in bile acid synthesis.
ii) Anion exchange resins: Examples are cholestyramine and colestipol. These act by binding irreversibly to bile salts, thus interfering with the enterohepatic circulation of bile salts between the gut and the liver and removing them from the body. Since bile salts are required for the emulsification and absorption of dietary fats, there is a resultant increase in hepatic LDL receptors which again result in an increased rate of removal of cholesterol from the blood for conversion to bile salts.
Question 11. Identify steps in problem-solving when counselling in the post-infarct situation.
Problem clarification; Goal setting; Examine possible solutions and their impact on the patient; Develop action plan agreed with the patient.