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.

 

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

Two specimens of aorta, cut so that the intimal space is visible. The left aorta is a relatively normal aorta with early changes with yellow/orange/white streaks on the relatively smooth intimal surface. The right aorta is an aorta with moderate atherosclerosis with more yellow/orange/white streaks but the surface is more bumpy/shaggy
DHPLC specimen C0324 Early and Moderate Atherosclerosis of Aorta

Severe and Very Severe Atherosclerosis

Key observations

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.

Two specimens of aorta, cut so that the intimal space is visible. The left specimen is an aorta with severe atherosclerosis which is mostly white/yellow streaks but the surface is bumpy/shaggy. The right specimen is an aorta with severe atherosclerosis. The entire surface is bumpy, covered with multiple yellow/orange plaques.
DHPLC specimen C0330 Severe and Very Severe Atherosclerosis of Aorta

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 Takeawats

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

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

 

 

the abdominal aorta is cut open to reveal the inner intimal surface. On the left of the image, the proximal aorta shows yellow-white atherosclerotic plaques. In the middle of the image, the entire luminal space is filled with a dark blood thrombus (clot) centered around a shaggy atherosclerotic plaque with a needle-thin opening for blood. The right image shows the abdominal aorta splitting into the two common iliac arteries.
DHPLC Specimen C0414 Thrombosis of Atherosclerotic Aorta

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

The abdominal aorta is opened at the level of the aneurysm, exposing the inside. The aneurysm has many layers, like an onion, with a dark blood clot (thrombus) just off the centre. The bottom of the aorta shows the bifurcation to the common iliac arteries. The top of the image shows the abdominal aorta dotted with yellow white atherosclerotic plaques
DHPLC specimen C0309 Atherosclerotic Aneurysm of Aorta

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

1. Fill in the blanks.On gross anatomy specimens, atherosclerotic plaques appear as _____ lesions. (indicate colour)

2. Finish the following sentence. Common clinical outcomes of advanced atherosclerosis include:
Select all that apply.

  • Aneurysm formation
  • Clot formation
  • Decreased blood pressure
  • Arythmias

3. Fill in the blank.

As atherosclerosis progresses, _____ can form on the luminal surface of the vessel, exposing underlying layers of the vessel wall.

4. Finish the following sentence. Aneurysm is usually a consequences of a weakened:

  • Tunica intima
  • Tunica media
  • Tunica externa

5. Fill in the blank.

_____ damage is necessary for atherosclerotic lesion initiation.

6. In atherosclerosis, lipid deposits can accumulate in both tunica intima and tunica media.

  • True
  • False

7. Fill in the blank.

_____ deposits in advanced atherosclerosis harden the vessel wall and make it brittle.

 

Answer Key

  1. Yellow
  2. Aneurysm formation, clot formation
  3. Ulcers
  4. Tunica media
  5. Endothelial
  6. True
  7. Calcium

Media Attributions

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Pathology Copyright © 2022 by Tetiana Povshedna is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, except where otherwise noted.

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