The Molecular Basis of Medicine
Step 1
Case 3
John Dorsey's Severe Chest Pains
Step Master: W. Marshall Anderson, Ph.D.
Tutors:W. Marshall Anderson, Ph.D.
Mary Ann Kirkish, Ph.D.
Susanna Alverez- Banks, Ph.D.
Case Author: W. Marshall Anderson, Ph.D.
Case Editors: Case Review Committee.
The Molecular Basis of Medicine
Step 1
Case 3 First Session
John Dorsey's Severe Chest Pains
John Dorsey is a 59-year-old black male who is admitted to the hospital with a three-hour history of severe chest pain. He describes similar but less severe pain in the chest during heavy exertion over the last year, but he thought that it was due to pain in the chest muscles. Mr. Dorsey describes himself as an insomniac and associates the beginning of his sleep problems with his first experiences of chest pain. This present pain is the worst he has ever experienced, and it is felt in both arms, his neck and back. He reports feeling sick to his stomach and having some trouble breathing.
Mr. Dorsey had no significant medical problems until three years ago when he began to have chest pains and noticed small growths on his hands. Mr. Dorsey is a real sports fan and eats a lot of fast foods, and enjoys potato chips and beer while watching the Sox, Bears, Hawks, and Bulls on TV.
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The Molecular Basis of Medicine
Step 1
Case 3 First Session Continued
Dr. Sigh, the emergency room physician, treats Mr. Dorsey with aspirin (325 mg orally) followed by nitroglycerin to relieve the acute pain, and she performs a quick physical exam.
Significantfindings on the physical exam are the following:
blood pressure -160/100
heart rate - 110/min
respirations are 20/min
no fever.
crackles in the bases of the lungs
systolic bulge at the left of the sternum
S4 gallop is heard over the ventricle and a systolic murmur is present
abdominal exam - normal
extremities - xanthomas over the tendons of the hands
pulses in the femoral and ankle arteries - decreased.
Electrocardiogram (EKG) shows evidence of acute infarction of the left anterior wall of the heart.
The nitroglycerin is controlling the acute pain, so morphine was not administered.
Blood was drawn for analysis, a beta blockerand a chest X-ray was ordered, and Mr. Dorsey was transferred to CCU.
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The Molecular Basis of Medicine
Step 1
Case 3 First Session
Continued
Lab Result for John Dorsey
JohnNormal Reference range
Electrolytes - normal
Blood count - normal
Troponin T positive (negative)
Troponin I positive (negative)
Arterial blood gas:
pH 7.46 7.36-7.45
pO2 65 90
pCO2 35 35-45
Chest x-ray: pulmonary edema, normal heart size
Lipid profile:
JohnNormalReferenceRange
Cholesterol 510 mg/dl (< 200 mg/dl)
HDL cholesterol 27 mg/dl (35-55 mg/dl)
LDL cholesterol 483 mg/dl (65-190 mg/dl)
Triglycerides 100 mg/dl (30-200 mg/dl)
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The Molecular Basis of Medicine
Step 1
Case 3 Second Session
Mr. Dorsey is treated with oxygen by mask and is given a dose of diuretic to reduce fluid accumulation in the lungs. The EKG shows injury to the anterior wall of the heart. An echocardiogram shows that the anterior wall of the left ventricle contracts poorly. Because of the short duration of his symptoms and the severity of the heart muscle dysfunction at this stage, he is given intravenous TNK-tPA. Three hours later he no longer has significant pain and he can breathe better. The following morning a repeat echocardiogram shows improved contraction.
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The Molecular Basis of Medicine
Step 1
Case 3 Second Session Continued
Mr. Dorsey comes from a large family with three brothers and four sisters. His father died of a massive heart attack at the age of 42 and two brothers and one sister have had heart attacks in their mid-thirties. Mr. Dorsey had a normal childhood, with the normal array of childhood illnesses, including chicken pox and measles. He smoked one pack a day for six years in his twenties, but hasn't smoked since then. He was hospitalized once, at the age of 31 for injuries from a traffic accident, but otherwise has had no significant medical problems, until the chest pains began three years ago. He has never been overweight. Mr. Dorsey is a mailman, so he gets some exercise every day walking from house to house, except Sunday. His wife has urged him to have his cholesterol checked, but he hasn't found time to get around to it.
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The Molecular Basis of Medicine
Step 1
Case 3 Second Session Continued
Mr. Dorsey is diagnosed as a heterozygous familial hypercholesterolemic. He has a few risk factors for coronary artery disease, yet, has abnormally high total cholesterol and high LDL values and the presence of xanthomas on the tendons of his hands. Following his hospital stay of ten days, he is put on a low fat, high fiber diet, with no eggs or organ meats, and given 1g of niacin before each meal and 20 mg Lipitor® orally once a day to control his blood cholesterol and to continue on the beta blocker until a re-evaluation at his next check-up in one month. He is enrolled in the cardiac patient exercise program at the hospital to increase his exercise level, and is told to cut out potato chips and beer while watching sports on TV. His liver function will be monitored at regular intervals.
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The Molecular Basis of Medicine
Step 1
Case 3
Objectives
1. Identify the roles of the various lipoproteins in lipid transport and metabolism.
2. Identify the enzymes that interact with lipoproteins.
3. Diagram the path of LDL delivery of cholesterol to cells, and explain the role of the LDL receptor.
4. Explain the roles of apoproteins in lipoprotein function.
5. Discuss the mechanism by which atherosclerotic plaques form.
6. List the primary risk factors in coronary artery disease.
7. List the proteins used in the diagnosis of myocardial infarction, and describe how the diagnosis is made on the basis of these values.
8. Describe the function of TNK –tPA in treating myocardial infarction patients. Describe other treatments that are commonly used.
9. List the functions of cholesterol in the body.
- Describe the mechanism of action of niacin and statins (Lipitor®).
- List the sources of cholesterol found in the body.
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The Molecular Basis of Medicine
Step 1
Case 3
Vocabulary
xanthoma
creatine kinase
infarction
pulmonary edema
HDL
LDL
triglycerides
tissue plasminogen activator
echocardiogram
Troponin T and I
niacin
statins
hypercholesterolemia
isoenzymes
cholesterol
chylomicrons
VLDL
apoproteins
lipoprotein lipase
LCAT
ACAT
LDL receptor
Lipitor®
Beta blocker
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The Molecular Basis of Medicine
Step 1
Case 3
Tutor's Guide
1. Abstract
Mr. Dorsey, a 59-year-old black male, is admitted to the hospital with severe chest pains. He has had similar but less severe pains during heavy exertion over the last year. Mr. Dorsey describes himself as an insomniac and associates the beginning of his sleep problems with his first experiences of chest pain. His present pain is also in both arms, neck and back. He is also nauseated and has trouble breathing. He has small fatty growths on his hands. Physical exam in the emergency room after giving oral aspirin followed by nitroglycerinfor acute pain, revealed crackles at the base of the lungs, a systolic bulge left of the sternum, a S4 gallop over the ventricle, and a systolic murmur. Xanthomas are present over the tendons of the hands. Pulse is decreased in the extremities. EKG shows acute infarction of left anterior wall of the heart. Lab findings reveal high positive test for Troponin T and I, cholesterol of 510/dl, HDL of 25 mg/dl, LDL of 350 mg/dl, and normal triglycerides. He is transferred to CCU, given a beta blocker and a diuretic for congestive heart failure, oxygen by mask and TNK-tPA. Echocardiogram before treatment shows left anterior heart wall contracting poorly, but improved contraction the morning after treatment. Mr. Dorsey has essentially only a few risk factors for coronary artery disease (e.g. does not smoke, is not overweight, and gets regular exercise). He does, however, like fast foods and potato chips, which are high in saturated fats (especially trans fats), is African American male and middle aged. He is released from the hospital after ten days, put on a low fat, high fiber diet and given niacin and Lipitor® to control blood cholesterol. He is also enrolled in the cardiac patient exercise program and is to continue the beta blocker until his next check-up at which time this medication will be re-evaluated. His liver function will be monitored regularly, to detect possible toxicity of Lipitor®.
2. Aims
This case is during the third week of the course. During this week the students will be finishing carbohydrate metabolism and covering lipid metabolism. A case on myocardial infarction is thus very germane to the subject matter. It should focus their attention on a major health problem in this country, make them aware of lipid metabolism and the function of lipoproteins in lipid metabolism and introduce them to some of the drugs used in treating coronary artery disease, including recombinant DNA product, such as TNK-tPA as well as drugs and dietary changes to control blood cholesterol. The student may want to learn something about cholesterol synthesis and degradation during this case and this would be appropriate. They may also want to delve deeply into nutrition at this point, which should be allowed, but not encouraged too much as they will get into it in a very big way during the last week of the course. As with the previous case, the students will begin to get an appreciation of how metabolism of various organs of the body interrelate, which will be important for the rest of the course.
Tutor's Guide continued
3. Sequence
As pointed out above this case illustrates the biochemical interrelationship of tissues and organs in the body. Later in the course they will be learning a lot more about this with purine metabolism, heme metabolism, and hormonal regulation.
4. Final diagnosis and outcome of the case
Based on the presence of only a few risk factors, yet high cholesterol, and LDL, low HDL, the presence of xanthomas on the hands and the severity of heart dysfunction, Mr. Dorsey is diagnosed as heterozygous hypercholesterolemic. Confirmation of this diagnosis would involve determining the LDL receptor content from a biopsy sample. It is hoped that the dietary changes together with niacin and Lipitor® will control Mr. Dorsey's blood cholesterol concentration, and that no more infarctions will occur. Since Mr. Dorsey gets exercise on his job, he should have no problems with the exercise program at the hospital and should be able to return to work soon. Since Lipitor®
can cause liver damage, his liver function will be monitored on a regular basis.
Guiding Questions
Session 1
What would cause such severe chest pains in this patient?
What is the nature of the growths on the patient's hands?
What is the significance of the patient liking "junk food"?
What is the significance of the elevated blood pressure?
What do aspirin and nitroglycerin do?
Why was a beta blocker prescribed for the patient?
Why was the patient given a diuretic?
What are xanthomas?
Why is positive Troponin T and Iin the blood sample significant in this patient?
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Why is the pO2 decreased?
Session 2
Why is it necessary to reduce fluid accumulations in the lungs in this patient?
What is the purpose of administering TNK-tPA? What other treatment options are available?
Would the patient's previous history of smoking contribute to his condition?
What are the risk factors for coronary artery disease?
What is hypercholesterolemia and what are its causes?
What is the mechanism of action of niacin and Lipitor®?
Why is the patient advised to eat a low fat, high fiber diet?
Why is the patient advised to have liver function tests done at regular intervals?
5. References
Cortner, J. A., et al. (1994) Familial combined hyperlipidemia in children: clinical expression, metabolic defects, and management. Curr. Prob. Ped., 24:295-305.
Humphries, S. E. (1994) The application of molecular biology techniques to the diagnosis of hyperlipidaemia and other risk factors of cardio-vascular disease. Annales de Biologie Clinique,. 52:67-75.
Cortner J. A., et al. (1993) Familial combined hyperlipidemia in children: clinical expression, metabolic defects, and management. J. Ped., 123:177-184.
Nordestgaard, B. G. And Tybjaerg-Hansen, A. (1992) IDL, VLDL, chylomicrons, and atherosclerosis. Eur. J. Epidemiol., 1:92-98.
Motulsky, A. G. (1992) Nutrition and genetic susceptibility to common diseases. Am. J. Clin. Nutr., 55:1244S-1245S.
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World Wide Web Resources:
Hyperlipidemia: URL:
Statin Drugs: URL:
Zocor URL:
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