Atherosclerosis and Angina
Gross Anatomy and Histopathology of Atherosclerosis
Tetiana Povshedna
Learning Objectives
By the end of this chapter, you will be able to:
- Identify macroscopic changes in the gross anatomy of the human aorta during different stages of atherosclerosis and its outcomes
- Relate key pathophysiological changes in the progression of atherosclerosis to the cell/tissue changes visible on the histological slide
- Interpret lipid and elastin histological stains
Stages of atherosclerosis (gross anatomy)
In this section, we will examine macroscopic changes that can occur in blood vessels of different sizes during atherosclerosis progression.
Early and moderate atherosclerosis
Please note: the gross specimen of the aorta appears flat because the artery (physiologically a tube) has been cut open to expose the luminal (inner) side of the vessel. Here, we are looking at the tunica intima – a place of atherosclerotic lesion initiation and a surface that physiologically in the human body is in direct contact with blood. Numerous openings on the aorta wall are origin sites of posterior intercostal arteries that branch off at this level of aorta and supply spine and rib cage with oxygenated blood.
Key observations:
Specimen A: mainly smooth intimal surface with early atherosclerotic lesions that appear as yellow cholesterol-containing plaques/streaks. Poorly defined pearly grey discoloration near openings of intercostal arteries demonstrates connective tissue proliferation
Specimen B: note the increased number and size of lesions compared to specimen A and the more irregular surface of the luminal side of the aorta
Severe and very severe atherosclerosis
Specimen C: Severe atherosclerosis. The wall of the aorta appears stiff and reduced in elasticity. The inner surface contained irregular nodules, patches, and streaks of atherosclerotic plaques that appear dirty yellow. Intima is absent in some areas, leaving surface ulcers. During specimen preparation, numerous calcium flecks were noticed, which rendered the vessel brittle.
Specimen D: Very severe atherosclerosis. The aorta is rigid and inelastic, with its surface completely altered by atherosclerotic lesions in various stages. Multiple surface ulcers are present. The brownish-black patches demonstrate hemorrhage under the atherosclerotic plaques. Thrombosis is occurring over some of the ulcerated lesions. The rigidity is due to calcium deposition.
Histopathology of atherosclerosis
We will examine the histopathology of atherosclerosis using two slides of atheroma of the aorta coming from the same patient – a 65 y.o. man with a history of hypertension – one of the main risk factors of atherosclerosis.
Both slides are stained with special stains (fat stain and elastic tissue stain) that allow for visualization of specific tissue components that would not be clearly identifiable by the classic H&E stain.
While examining tissue slides, please note epithelial damage – an initial step of atherosclerosis progression that triggers subsequent inflammation and atherosclerotic plaque formation.
Histopathology of atherosclerosis (aorta) by Tetiana Povshedna licensed under CC BY 4.0 created with BioRender.com. Histology slides are DHPLC specimens PATH 425-032 (fat stain) and PATH 425-033 (elastin stain)
Fat Tissue Stain: Key Takeaways
- Irregularly thickened tunica intima as a result of lipid accumulation
- Numerous lipid deposits in both tunica intima and tunica media
On a cellular level, this stage of atherosclerosis development is associated with the pro-inflammatory state, macrophage recruitment, and foam cell formation with subsequent necrotic core development.
Elastin Stain: Key Takeaways
- Irregularly thickened tunica intima; loss of elastic fibers in tunica intima (compare this elastic stain to an example of the normal human aorta in Gross anatomy and histology of normal aorta and note the amount of elastic fibers in tunica intima)
- Elastic tissue appears compressed and fragmented in the superficial layers of tunica media. This fragmentation and weakening of the aorta wall might facilitate the formation of aneurysm
- On higher magnification, cholesterol crystals appear as stellate empty spaces in tunica intima
- Areas of calcification appear as dark dense spots within tunica intima
Type your key takeaways here.
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While all the histological slides and gross anatomy specimens above focused on various regions of aorta as a site of atherosclerotic plaque formation, coronary arteries are also one of the common and clinically relevant sites of atherosclerosis. Plaque formation within these arteries can cause hypoxia of the heart muscle which, if left untreated, can lead to a heart attack.
The video below examines the key features of atherosclerosis in coronary arteries. Clinically, these changes would reflect the pathophysiology of ischemic heart disease.
Histopathology of atherosclerosis (coronary artery). Created and presented by Jonathan Bush. Histology slide is from private collection.
Key takeaways:
- numerous immune cells in tunica externa reflect inflammatory process triggered by atherosclerosis
- a blood clot is obstructing the lumen, making tunica intima hard to identify
- fibrotic areas (appear pale pink and do not contain a lot of cell nuclei) reflect lipid accumulation
- foam cells that engulfed oxidized LDL in tunica media
Clinical outcomes of severe atherosclerosis (gross anatomy)
Thrombosis of atherosclerotic aorta
The formation of a clot is one of the common clinical outcomes of severe atherosclerosis. Thrombosis-induced ischemia can result in heart attack or stroke, depending on location. Clot formation as a result of atherosclerosis in coronary vessels can block the blood flow to the heart, and cause tissue damage as a result of hypoxia. Similar scenarios can occur anywhere along the vascular tree, including the brain (stroke), lower limb (peripheral artery disease), etc.
This specimen demonstrates a case of thrombosis in the abdominal aorta as a result of atherosclerosis.
Patient history:
An elderly man with a history of peripheral artery disease – a manifestation of atherosclerosis in lower limbs, which resulted in bilateral leg amputation two years previously. Chief complaint on admission – pain. Cause of death – pneumonia; autopsy revealed generalized atherosclerosis.
The specimen demonstrates distal abdominal aorta as it divides into the right and left common iliac arteries.
Key observations:
- narrowing of the distal aorta by a dark thrombus which extends into common iliac arteries
- thickening of the aorta wall – numerous yellow atherosclerotic plaques that narrow the lumen
- typical location of the plaque and thrombus – bifurcation of a large vessel where the laminar flow becomes turbulent
Aneurysm of atherosclerotic aorta
Severe atherosclerosis can progress towards aneurysm, where the muscular layer of the vessel weakens and creates a bulge that can rupture and lead to internal bleeding.
This case demonstrates atherosclerotic aneurysm of the abdominal aorta.
Patient history:
75 y.o. man with a known abdominal aortic aneurysm, presented with epigastric pain for several days. Physical examination of abdomen revealed a non-painful mass about 10 cm in diameter. Aneurysm dissection was suspected. The autopsy revealed atherosclerosis of coronary vessels, as well as an atherosclerotic abdominal aneurysm with a thrombus.
Key observations:
- compare and contrast the diameter of abdominal aorta and aneurysm
- note numerous atherosclerotic plaques in the proximal part of the aorta
- the lumen of the aneurysm if partially filled with a mural thrombus
- typical location of atherosclerosis/aneurysm – at the bifurcation of the abdominal aorta into right and left common iliac arteries
Compare and contrast the diameter of the abdominal aorta in the above figure and the one below of DHPLC specimens C0414 and C0309
Section review
On gross anatomy specimens, early atherosclerotic lesions appear as yellow streaks/patches on the luminal side of the vessel. As the severity of atherosclerosis increases, atherosclerotic plaques grow in size and number and can cause ulceration. Advanced atherosclerotic vessels have an irregular luminal surface, numerous plaques, areas of calcification, ulceration, and clot formation. One of the most common clinical outcomes of advanced atherosclerosis is an aneurysm or clot formation.
Histologically, lipid deposits are visible within the tunica intima and tunica media of atherosclerotic vessels. Endothelial damage, which is necessary for lesion initiation, is often present. During the advanced stages, cholesterol crystals and calcium deposits can be visualized in tunica intima, while tunica media can appear fragmented.
Review questions
(also, tunica interna) innermost lining or tunic of a vessel
bleeding
same as atherosclerotic plaque
elevated blood pressure
middle layer or tunic of a vessel (except capillaries)
abnormal ballooning/ widening of the blood vessel wall cause by it's weakness. Aneurysm rupture is very dangerous and often fatal
lack of oxygen supply to the tissues
branches of the ascending aorta that supply blood to the heart; the left coronary artery feeds the left side of the heart, the left atrium and ventricle, and the interventricular septum; the right coronary artery feeds the right atrium, portions of both ventricles, and the heart conduction system
(also, tunica adventitia) outermost layer or tunic of a vessel (except capillaries)
insufficient blood flow to the tissues
a large artery that carries oxydenated blood to lower limbs, pelvis, and reproductive organs
part of the blood vessel where it splits in 2 branches
type of fluid flow in which fluid travels smoothly
type of fluid flow in which fluid undergoes irregular fluctuations and mixing
upper abdomen, below the ribs
injury to the inner layer of the vessel, separation (tear) of blood vessel wall that allows for blood to flow between the layers; a medical emergency
arteries that supply heart muscle
