Case Study 3 - Atherosclerosis Flashcards
A 64 year old man attends our clinic. He is known to
have type 2 diabetes and has also been a smoker since the age of 15 years. He has developed a large wound on the bottom of his foot that has gradually got bigger and bigger. It is very painful and smells a lot which is becoming embarrassing for him. He takes the dressing
off of his foot and leg in the clinic and shows you the wound. (1)
Describe what is shown in the picture.
Image
A 64 year old man attends our clinic. He is known to
have type 2 diabetes and has also been a smoker since the age of 15 years. He has developed a large wound on the bottom of his foot that has gradually got bigger and bigger. It is very painful and smells a lot which is becoming embarrassing for him. He takes the dressing
off of his foot and leg in the clinic and shows you the wound. (1)
What do you think has caused this to develop?
Atherosclerosis in the limb arteries leading to necrosis and ischemia, Issues with diabetes and diabetic food, Neuropathic problem because of diabetes (diabetes is a risk factor of atherosclerosis because high blood sugar is toxic to endothelial cells and cause injury), Venous disease most likely atherosclerosis of the arteries
A 64 year old man attends our clinic. He is known to
have type 2 diabetes and has also been a smoker since the age of 15 years. He has developed a large wound on the bottom of his foot that has gradually got bigger and bigger. It is very painful and smells a lot which is becoming embarrassing for him. He takes the dressing
off of his foot and leg in the clinic and shows you the wound.
What is atherosclerosis and what is the pathological process that leads to its development?
Atherosclerosis is a condition characterized by the hardening, thickening, and loss of elasticity of the arteries. The pathological process leading to its development involves several key steps, as you mentioned:
Endothelial Dysfunction/Injury: The endothelial cells lining the inner surface of blood vessels play a crucial role in maintaining vascular health. Factors like high blood pressure, smoking, and diabetes can lead to endothelial dysfunction or injury.
Increased Permeability: In response to endothelial dysfunction, the endothelial cells become more permeable. This allows the entry of low-density lipoprotein (LDL) cholesterol from the bloodstream into the intima layer of the blood vessels.
Formation of Foam Cells: LDL cholesterol undergoes oxidation in the intima layer, and macrophages recognize the oxidized LDL as foreign and attempt to engulf it through phagocytosis. This process results in the formation of foam cells, which are essentially dead macrophages containing lipids.
Formation of Fatty Streaks: Foam cells accumulate in the intima layer, creating fatty streaks. Fatty streaks are considered early lesions of atherosclerosis.
Smooth Muscle Cell Activation: Growth factors are recruited, leading to the activation of smooth muscle cells in the arterial wall’s medial layer.
Migration and Proliferation of Smooth Muscle Cells: Activated smooth muscle cells migrate from the medial layer to the intima layer. There is also increased proliferation of smooth muscle cells in the intima.
Collagen Production: The activated smooth muscle cells produce collagen, contributing to the formation of a fibrous cap over the fatty streak.
Plaque Formation: The combination of foam cells, smooth muscle cells, and collagen forms a plaque in the arterial wall. This plaque can grow over time and may eventually lead to the narrowing or complete blockage of the artery.
A 64 year old man attends our clinic. He is known to
have type 2 diabetes and has also been a smoker since the age of 15 years. He has developed a large wound on the bottom of his foot that has gradually got bigger and bigger. It is very painful and smells a lot which is becoming embarrassing for him. He takes the dressing
off of his foot and leg in the clinic and shows you the wound.
What are the modifiable risk factors for developing atherosclerosis?
Diabetes mellitus type 2, smoking, untreated high BP, elevated CRP, inactivity (rather than obesity), dyslipidemia (high LDL + low HDL)
A 64 year old man attends our clinic. He is known to
have type 2 diabetes and has also been a smoker since the age of 15 years. He has developed a large wound on the bottom of his foot that has gradually got bigger and bigger. It is very painful and smells a lot which is becoming embarrassing for him. He takes the dressing
off of his foot and leg in the clinic and shows you the wound.
What are the non-modifiable risk factors for developing atherosclerosis?
Advancing age, male, genetic predisposition, inherited abnormalities, untreated infections
A 64 year old man attends our clinic. He is known to
have type 2 diabetes and has also been a smoker since the age of 15 years. He has developed a large wound on the bottom of his foot that has gradually got bigger and bigger. It is very painful and smells a lot which is becoming embarrassing for him. He takes the dressing
off of his foot and leg in the clinic and shows you the wound.
What are the pathological changes that can happen to an atherosclerotic plaque?
High Blood Pressure (Hypertension) and Rupture: Elevated blood pressure can contribute to the rupture of an atherosclerotic plaque. Hypertension puts increased stress on the arterial walls, and if the fibrous cap covering the plaque is weakened, the increased pressure can lead to the rupture of the plaque. Rupture can expose the plaque’s contents, triggering a cascade of events that may result in blood clot formation and arterial blockage.
Plaque Destabilization: Atherosclerotic plaques can become unstable due to various factors, including inflammation and the breakdown of the fibrous cap. Unstable plaques are more prone to rupture, leading to the formation of blood clots and potentially causing blockages in blood vessels.
Erosion due to Chronic Hypertension: Chronic hypertension can contribute to the erosion of the blood vessel wall, particularly at the site of the plaque. The constant sheer stress caused by high blood pressure may lead to the gradual wearing away of the endothelial lining, potentially exposing the plaque and promoting further damage.
Hemorrhage into Plaque as a Result of Inflammation: Inflammation within the plaque can lead to the development of a vulnerable, unstable plaque. Inflammatory processes may weaken the fibrous cap, making it more susceptible to rupture. Hemorrhage into the plaque can occur, leading to the expansion of the plaque volume and causing further narrowing (stenosis) of the blood vessel.
These pathological changes highlight the dynamic and complex nature of atherosclerosis. The consequences of these changes can include the formation of blood clots, acute cardiovascular events (such as heart attacks or strokes), and compromised blood flow to various organs and tissues. In the case of the 64-year-old man with type 2 diabetes and a foot wound, these processes may contribute to the severity and complications of his condition.
A 64 year old man attends our clinic. He is known to
have type 2 diabetes and has also been a smoker since the age of 15 years. He has developed a large wound on the bottom of his foot that has gradually got bigger and bigger. It is very painful and smells a lot which is becoming embarrassing for him. He takes the dressing
off of his foot and leg in the clinic and shows you the wound.
What medications could be used to modify some of these risk factors and how do they do this?
Statins:
How they work: Statins are cholesterol-lowering medications that inhibit the enzyme HMG-CoA reductase, which plays a key role in cholesterol synthesis. By reducing cholesterol levels, especially low-density lipoprotein (LDL) cholesterol, statins help stabilize and potentially shrink atherosclerotic plaques.
Role in risk modification: Statins are essential for managing dyslipidemia (abnormal lipid levels) and reducing the risk of cardiovascular events such as heart attacks and strokes.
Antihypertensive Medications:
How they work: Antihypertensive medications, including classes such as ACE inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers, and diuretics, aim to lower blood pressure and reduce the strain on the cardiovascular system.
Role in risk modification: Controlling hypertension is crucial in preventing further damage to blood vessels and reducing the risk of complications associated with atherosclerosis, such as plaque rupture.
Anticoagulants/Antiplatelet Medications:
How they work: Anticoagulants (e.g., warfarin) and antiplatelet medications (e.g., aspirin) interfere with the blood clotting process, reducing the risk of clot formation.
Role in risk modification: These medications are often prescribed to prevent blood clots, which can be especially important in individuals with atherosclerosis to prevent complications such as heart attacks and strokes.
Antidiabetic Medications:
How they work: Medications for diabetes management can include oral hypoglycemic agents (e.g., metformin) and insulin. These medications aim to control blood glucose levels and reduce the impact of diabetes on blood vessels.
Role in risk modification: Proper glycemic control is crucial in preventing diabetes-related complications, including atherosclerosis. By managing blood glucose levels, these medications contribute to overall cardiovascular health.
Low-Dose Aspirin:
How it works: Aspirin is an antiplatelet medication that inhibits the formation of blood clots by interfering with platelet function.
Role in risk modification: Low-dose aspirin is often prescribed to individuals at high risk of cardiovascular events. It can help prevent blood clot formation and reduce the risk of complications in patients with atherosclerosis.
A 64 year old man attends our clinic. He is known to
have type 2 diabetes and has also been a smoker since the age of 15 years. He has developed a large wound on the bottom of his foot that has gradually got bigger and bigger. It is very painful and smells a lot which is becoming embarrassing for him. He takes the dressing
off of his foot and leg in the clinic and shows you the wound.
The GP refers him to the vascular surgeons. They request an ultrasound scan of the arteries of
his leg. The result shows a stenosis of the popliteal artery. When he returns to the clinic for the results, he reports that there have been further changes to his foot.
What has happened to our patient’s toe and why? (2)
Image
A 64 year old man attends our clinic. He is known to
have type 2 diabetes and has also been a smoker since the age of 15 years. He has developed a large wound on the bottom of his foot that has gradually got bigger and bigger. It is very painful and smells a lot which is becoming embarrassing for him. He takes the dressing
off of his foot and leg in the clinic and shows you the wound.
The GP refers him to the vascular surgeons. They request an ultrasound scan of the arteries of
his leg. The result shows a stenosis of the popliteal artery. When he returns to the clinic for the results, he reports that there have been further changes to his foot.
What are the two main types of necrosis? What are the pathological features?
Liquefactive Necrosis:
Pathological Features:
Structure of the cell is destroyed, leading to the conversion of tissue into a liquid, often described as a viscous, liquid mass.
Complete digestion of cellular components occurs.
Commonly associated with bacterial or fungal infections, where enzymes released by pathogens or inflammatory cells lead to the liquefaction of tissue.
Denaturation of intracellular proteins is a key mechanism.
Coagulative Necrosis:
Pathological Features:
Caused by a decrease in blood flow (ischemia) leading to hypoxia.
Mainly associated with infarction, which is the localized death of tissue due to lack of blood supply.
Results in the preservation of the tissue’s basic architecture for a certain period.
Pathological factors include transient inhibition of proteolysis, causing ischemia.
Nuclear changes occur, including:
Nuclear Fading (Karyolysis): Mediated by the action of DNases and RNases, leading to the dissolution of chromatin.
Pyknosis: Nuclear shrinkage due to chromatin condensation, resulting in a smaller, denser nucleus.
Karyorrhexis: Nuclear fragmentation caused by the rupture of the nuclear membrane.
A 49 year old lady comes to see her GP for a review of her blood pressure.
She was diagnosed with hypertension 4 months ago and was prescribed
Ramipril to treat this. She reports that she has had a persistent cough but is otherwise feeling well.
What is meant by the term arteriolosclerosis and what is the difference to atherosclerosis?
Arteriolosclerosis:
Definition: Arteriolosclerosis refers to the thickening and hardening of small arteries and arterioles. It is a condition that primarily affects the smaller vessels in the arterial system.
Causes: Arteriolosclerosis is associated with aging, high blood pressure (hypertension), and conditions like diabetes. Chronic hypertension, in particular, can contribute to the development of arteriolosclerosis.
Atherosclerosis:
Definition: Atherosclerosis is the deposition of fatty materials (such as cholesterol and triglycerides) inside the arteries, leading to the formation of atheromas (plaques). It predominantly affects medium to large arteries.
Causes: The primary cause of atherosclerosis is endothelial injury, often resulting from factors such as oxidative stress. Conditions like hypertension, smoking, diabetes, and high levels of LDL cholesterol contribute to the development and progression of atherosclerosis.
Difference between Arteriolosclerosis and Atherosclerosis:
Vessel Size: Arteriolosclerosis specifically involves small arteries and arterioles, while atherosclerosis primarily affects medium to large arteries.
Location: Arteriolosclerosis is more localized to smaller vessels, often impacting organs and tissues with a dense network of small arteries. Atherosclerosis is commonly found in larger arteries throughout the body.
Associations: Arteriolosclerosis is strongly associated with aging, hypertension, and diabetes. Atherosclerosis is linked to a broader range of risk factors, including hypertension, smoking, diabetes, and elevated cholesterol levels.
Lesion Type: Arteriolosclerosis involves thickening of the vessel walls without the prominent lipid deposition seen in atherosclerosis. Atherosclerosis, on the other hand, is characterized by the accumulation of lipids, inflammation, and the formation of atheromas/plaques within the arterial walls.
A 49 year old lady comes to see her GP for a review of her blood pressure.
She was diagnosed with hypertension 4 months ago and was prescribed
Ramipril to treat this. She reports that she has had a persistent cough but is otherwise feeling well.
How does atherosclerosis occur in people with hypertension?
Shear Stress and Endothelial Injury:
Hypertension Effect: Hypertension leads to increased shear stress on the walls of blood vessels, particularly in areas of turbulent blood flow.
Endothelial Response: The endothelial cells lining the blood vessels respond to this increased stress, and over time, chronic exposure to high blood pressure can result in endothelial injury.
Loss of Endothelial Integrity:
Effect on Endothelium: The continuous stress on the endothelial cells can lead to a loss of integrity in the endothelial lining.
Compromised Function: The compromised endothelial function allows for increased permeability, making it easier for substances, including lipids like LDL cholesterol, to penetrate the vessel wall.
Oxidation of LDL Cholesterol:
Influx of LDL: Due to the compromised endothelial barrier, there is an increased influx of low-density lipoprotein (LDL) cholesterol from the bloodstream into the vessel wall.
Oxidation: Within the vessel wall, LDL cholesterol can undergo oxidative modifications. Oxidized LDL is recognized as foreign or abnormal by the immune system.
Inflammatory Response:
Immune Cells Recruitment: Monocytes and macrophages are recruited to the site of endothelial injury and oxidized LDL deposition.
Phagocytosis: Macrophages engulf the oxidized LDL in a process called phagocytosis. This leads to the formation of foam cells, a hallmark of early atherosclerotic lesions.
Formation of Atherosclerotic Plaque:
Proliferation and Migration: The recruited immune cells, particularly macrophages, release cytokines and growth factors. This stimulates the proliferation and migration of smooth muscle cells from the arterial wall’s media layer to the intima layer.
Collagen Production: Smooth muscle cells produce collagen, contributing to the formation of a fibrous cap over the atherosclerotic plaque.
Atherosclerosis Progression:
Chronic Inflammation: The ongoing inflammatory response, coupled with the accumulation of lipid-laden foam cells and smooth muscle cells, leads to the progression of atherosclerosis.
Plaque Development: The atherosclerotic plaque may undergo changes over time, potentially leading to complications such as plaque rupture or thrombosis.
A 49 year old lady comes to see her GP for a review of her blood pressure.
She was diagnosed with hypertension 4 months ago and was prescribed
Ramipril to treat this. She reports that she has had a persistent cough but is otherwise feeling well.
This is a picture of a muscular artery. Label the features. (3)
Image
A 49 year old lady comes to see her GP for a review of her blood pressure.
She was diagnosed with hypertension 4 months ago and was prescribed
Ramipril to treat this. She reports that she has had a persistent cough but is otherwise feeling well.
What is the pathogenesis of hyperplastic arteriolosclerosis? What is its most common cause and which blood vessels are mostly affected?
Hyperplastic arteriolosclerosis is a type of arteriolosclerosis characterized by the thickening of the arterial walls due to concentric proliferation of smooth muscle cells. This process results in a distinctive microscopic appearance often referred to as “onion skin.”
Pathogenesis of Hyperplastic Arteriolosclerosis:
Hypertrophy of Smooth Muscle Cells:
The process begins with the hypertrophy (enlargement) of smooth muscle cells in the media layer of small arteries and arterioles.
Reduplication of Elastic Laminae:
As smooth muscle cells undergo hypertrophy, there is a reduplication of elastic laminae, which are layers of elastic fibers in the arterial wall.
Growth of New Cells in the Intima:
Simultaneously, there is the growth of new cells in the intima layer, contributing to the thickening of the arterial wall.
Deposition of Collagen:
Collagen deposition occurs, further contributing to the structural changes in the arterial wall.
Concentric Proliferation:
The proliferation of smooth muscle cells is concentric, meaning it occurs in a circular or layered fashion around the vessel lumen.
Onion Skin Appearance:
The combination of hypertrophied smooth muscle cells, reduplicated elastic laminae, and collagen deposition gives rise to the characteristic microscopic appearance known as “onion skin.”
Most Common Cause and Affected Blood Vessels:
Most Common Cause: Hyperplastic arteriolosclerosis is often associated with severe hypertension, especially malignant hypertension. Malignant hypertension is a form of very high blood pressure that can lead to rapid and severe damage to small arteries.
Affected Blood Vessels: This type of arteriolosclerosis primarily affects small arteries and arterioles, particularly those supplying organs such as the kidney. The renal arterioles are commonly affected in hypertensive conditions, leading to changes in the kidney’s microvasculature.
A 49 year old lady comes to see her GP for a review of her blood pressure.
She was diagnosed with hypertension 4 months ago and was prescribed
Ramipril to treat this. She reports that she has had a persistent cough but is otherwise feeling well.
The GP next has a look at our patient’s medication list. He notices that Ramipril is on the list.
But….he can’t remember what this does or how it works!
What class of drug is Ramipril from?
Angiotensin-converting enzyme (ACE) inhibitor
A 49 year old lady comes to see her GP for a review of her blood pressure.
She was diagnosed with hypertension 4 months ago and was prescribed
Ramipril to treat this. She reports that she has had a persistent cough but is otherwise feeling well.
The GP next has a look at our patient’s medication list. He notices that Ramipril is on the list.
But….he can’t remember what this does or how it works!
What is Ramipril used to treat?
Ramipril is a medicine widely used to treat high BP (hypertension) and heart failure. It’s also prescribed after a heart attack. Ramipril helps prevent future stokes, heart attacks and kidney problems.
Therefore, it is used to treat hypertension, congestive heart failure, kidney disease, and diabetes
