MVST BOD & NST Part IB Thurs.
5th &
Pathology Practical
Class 22 CARDIOVASCULAR
DISEASE
PROBLEM SOLVING EXERCISES – ATHEROSCLEROSIS & CARDIOVASCULAR DISEASE
PSE: PART I:
ATHEROSCLEROSIS
AIM
To understand the nature and factors influencing development and progression of atherosclerosis.
ATHEROSCLEROSIS:
INTRODUCTION
One of the most common causes of death in the Western world is due to the consequences of coronary artery disease including myocardial ischaemia and myocardial infarction. This most often results from atherosclerosis in the coronary arteries. The process of atherosclerosis leads to formation of atherosclerotic plaques, which have a fibrous cap overlying a soft centre, composed of lipid and necrotic material. Atherosclerotic plaques may rupture, stimulating the development of thrombus. A large thrombus on the surface of a ruptured plaque can cause obstruction of the lumen of the artery – and this is the commonest cause of myocardial infarction. Spasm of the coronary arteries and emboli in the coronary arteries are occasionally involved, but less frequently. To prevent atherosclerosis, it is important to understand the underlying processes (see diagram below) and the relevant risk factors.
Risk factors for atherosclerosis include: 4 major risk factors - smoking, hypertension, diabetes mellitus, hyperlipidaemia, and several minor risk factors - increasing age, male sex (hormonal effects on blood lipid levels), family history, obesity, & certain ethnic origins.
The AORTA and larger arteries are elastic arteries. Arteries have 3 layers: tunica intima (inner layer in contact with blood in the lumen), tunica media (middle layer containing smooth muscle cells), and tunica adventitia (outer layer composed of supporting fibroconnective tissue with capillaries and nerves). The 3 layers are separated by 2 elastic laminae. In H&E sections, the elastic laminae appear pink and usually have a wavy appearance. The intima is the innermost layer and lies between the innermost elastic lamina and the endothelium. At birth the intima consists solely of the endothelium with its basement membrane. Within the arterial system including the aorta and the coronary arteries, there is uniform thickening by smooth muscle cells and fibrous tissue, to form so-called diffuse intimal thickening (DIT).
ATHEROSCLEROSIS:
PROBLEM-SOLVING EXERCISE
First, look at the photographs of macroscopic specimens of normal aorta (P22.1) and atherosclerotic aorta (P22.2), then examine the photomicrographs of microscope slides of normal aorta (P22.3) and an atherosclerotic plaque (P22.4) taken from atherosclerotic aorta. Proceed to the diagram of atherogenesis and answer the problem-solving questions about this pathological process.
P22.1
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N_CR_AO_17.jpg |
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P22.2 Atherosclerotic Aorta
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A_VA_AZ_AO_41.jpg |
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N_CR_AO_18.jpg |
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This aorta was from an 18-year-old girl killed in a road traffic accident.
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A_VA_AZ_AO_42.jpg |
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This aortic
tissue is from an 80-year-old man who had thrombosis over plaques in his
abdominal aorta.
Thrombus has formed over the ruptured surface of an atherosclerotic plaque containing abundant lipid. Within the plaque, there are clear central areas which originally contained necrotic tissue and lipid, (the latter dissolved out during the processing of the tissue), covered by a fibrous cap. In fresh tissue, the necrotic centre of these lesions is very soft with a fancied resemblance to porridge, hence the lesion is called atheroma (from the Greek word, athera = gruel). The central necrotic material contains many cholesterol clefts (crystal-like formations of cholesterol that dissolve out during tissue processing).
Macrophages are present within the plaque, whose cytoplasm is filled with many lipid-laden vacuoles. These appear after tissue processing as clusters of clear bubbles, hence the descriptive term “foam cells”.
This DIAGRAM OF ATHEROGENESIS shows the major
components important in the formation of an atherosclerotic plaque and its
progression.
Monocytes (in blood) enter the Tunica Intima becoming macrophages and these take up the LDLs and lipid to become Foam cells/Foamy macrophages.
ATHEROSCLEROSIS:
PROBLEM-SOLVING QUESTIONS:
QA. At the earliest stages of plaque development, what influences lipid circulating in the blood, in the form of Low Density Lipoprotein (LDL), to enter the tunica intima of the artery wall?
QB. What stimulates blood monocytes to enter the arterial wall (becoming tissue macrophages) at the same site as the LDL?
QC. If the macrophages can phagocytose LDL forming “foam cells” (containing intracellular lipid), how does the extracellular lipid pool form and grow larger? (seen as cholesterol crystals and lipid gruel in your section).
QD. What triggers the smooth muscle cells in the tunica media to migrate to the tunica intima, proliferate and secrete extracellular matrix?
QE. Can you assign the four major risk factors (smoking, hypertension, diabetes mellitus & hyperlipidaemia) to pathogenic events in atherosclerosis?
QF. What makes an atherosclerotic plaque rupture? Why is this an important event?
PSE: PART II: CARDIOVASCULAR PATHOLOGY
AIM
To understand and gain facility in interpreting the relationship between the pathological processes of atherogenesis, thrombosis, embolism and infarction on the one hand, and their capacity to generate complex patterns of disease on the other.
CASE
A 64-year old retired executive, whilst pottering in his garden, developed central crushing chest pain that radiated down his left arm. He was rushed into hospital where an electrocardiogram showed evidence of a recent myocardial infarction. A few hours later, blood tests showed elevation in the serum levels of both Troponin-I and the MB isotype of creatine kinase (an intracellular protein and an intracellular enzyme respectively, normally present only in cardiac myocytes).
The two photographs (P22.5 and P22.6) show the microscopic appearances of myocardium 24 hours and 8 days after an episode of this type (from different cases), but may not have been numbered in the right order.
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A_VA_IF_HT_64.jpg |
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A_VA_IF_HT_65.jpg |
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Q1. Work out, and justify as fully as possible, whether P22.5 was taken earlier than P22.6 or the other way round.
Q2. What changes in the myocardial cells can explain (i) the raised levels of Troponin-I and MB isotype of creatine kinase; (ii) the pain?
Q3. What might you have found in a microscope section of the coronary artery, which supplied the infarcted wall of the left ventricle?
Five days after the initial admission to hospital, he was found unconscious on the floor. When he regained consciousness, he was no longer able to move his arm or leg on his right side. His face was also paralysed on this side.
Two days later, he developed severe abdominal pain and bloody diarrhoea. It was decided not to undertake surgery, given his condition. Instead, he was nursed and sedated. He died 2 days later and a post-mortem was performed.
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Q4. What changes to the intestines can you see? How has this occurred? Why would this cause death? |
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Q5. What has occurred to the brain and why did it occur? |
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A_VA_IF_KD_10.jpg |
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A_VA_IF_KD_11.jpg |
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Q6. An abnormality was found in his kidney at post mortem. What shape is it? What does this suggest it is? Correlate the naked eye changes with the histological appearances. Q7. Can you draw a flow diagram summarising the sequence of events from the pathological processes that triggered the myocardial infarction, to changes affecting brain, kidney & intestines, eventually leading to death? |
Please remember to collect an answer sheet at the end
of the Problem Solving Exercise.