Weatherly's Woes - Blood Vessels

ATHEROSCLEROSIS

Plaque deposition in the tunica intima of medium and large arteries.

Abdominal Aorta > Coronaries > Popliteal > Carotids > Circle of Willis

Atherosclerosis MOA - a generalized state of inflammation is seen with smoking, diabetes and hypertension → endothelial cells are hurt → if you have high cholesterol, some of the excess LDL will slip through the cracks in the endothelium and accumulate within the walls of the vessel (intima) → macrophages arrive, and eat oxidized LDL → the macrophages get fat, and turn into foam cells→ they are too thiqq to pass through gaps between endothelial cells, so they accumulate in the intima (fatty streaks) → when foam cells die, cytokines are released → cytokines attract smooth muscle cell migration from the tunica media (PDGF/FGF involved) → smooth muscle cells proliferate and extra-cellular matrix is laid down → fibrous plaque → complex atheromas (large size) → calcification (seen on CT) → atheroma outgrows its blood supply → necrotic core develops, which is prone to intraplaque hemorrhage → plaque rupture may occur, spilling all of the built up goop inside the vessel wall (fat, calcium, collagen) into the blood → the goop is highly inflammatory and highly pro-clotting, so a blood clot will form, and this blood clot can occlude the lumen and cause a heart attack!

Vocabulary

Fibrous Cap - the blood vessel wall overlying an atherosclerotic plaque. Rich in collagen, which is laid down by vascular smooth muscle cells in the presence of cytokines and growth factors (PDGF, FGF, endothelin-1)

Stable Plaque - this plaque has a thick cap, minimal lipid cores and minimal inflammation so it’s unlikely to rupture. It can produce stable angina if the plaque grows large enough to narrow the vessel 70% or more. Treatment with stents can help to maintain vessel patency.

Unstable Plaque - this plaque has a thin cap, large lipid core and dense inflammatory infiltrates so it’s likely to rupture. Like a volcanic eruption, the plaque contents (fat and inflammatory products) explode out and promote clot formation and vasoconstriction. The clot can either occlude locally (MI) or embolize to a distant site (carotid → stroke). Once a plaque occludes 30% of the vessel, it is considered capable of causing a heart attack. There will be no angina with patients between 30% and 70% patency, but they are at risk of sudden MI and death.

Timeline

Pre-Clinical Phase - asymptomatic atherosclerosis that begins in children and young adults that lasts for decades. Mostly fatty streaks

Clinical Phase - symptomatic portion that occurs in middle / old age after a lifetime of atherosclerosis.

Modifiable Risk Factors for atherosclerosis (descending order of importance)

Diabetes - non-enzymatic glycosylation damages endothelial cells, and glucose promotes inflammation
High LDL Hyperlipidemia - LDL accumulates faster (a low HDL is not as important as a high LDL)
Smoking - directly damages endothelium
Hypertension - shear force that pushes against the endothelial cells causing injury
Obesity - excess adipose leading to a hyperinflammatory state

Non-Modifiable Risk Factors for atherosclerosis (descending order of importance)

History of previous MI / stroke - single strongest predictor of a future MI
Old age - people below 55 shouldn’t have heart attacks
Family hx of ACS or sudden unexplained death in nuclear family member <55 male or <65 female. Very important.
Male gender
Ethnicity (Black or SE Asian)

Changeable Influences - poverty, stress, poor diet, exposure to smoke/fumes/pollution, access to healthcare

Random note on calcium

Calcium can be seen on CT scans. That makes CT’s useful for finding atherosclerosis. If you perform a CT of the heart, you can calculate something called the Coronary Artery Calcium (CAC) Score, which is used to stage CAD. However, CTs are costly, radioactive and the CAC score isn’t as sensitive as we’d like

AORTIC ANEURYSMS

There are four major forces that weaken the Aorta: Trauma, Atherosclerosis, Syphilis and Marfans (a connective tissue disease). When blood vessels weaken, high hydrostatic forces (hypertension) can cause the wall to balloon. Some aneurysms grow slowly. Some grow fast. But all aneurysms grow, and all eventually rupture. Aneurysms can occur on any artery in the body. The most clinically significant aneurysms occur in the brain and on the aorta. The aorta has a thoracic half and an abdominal half. The thoracic half is protected from aneurysms because it has a vasa vasorum. The abdominal half is very prone to atherosclerosis and aneurysms because it lacks a vasa vasorum (below the level of the renal arteries). But the Vasa Vasorum isn’t perfect -- it’s a target for Syphilis (which likes to infect small blood vessels).

Thoracic aortic aneurysms are very rare nowadays. That’s because the most common cause is (or rather was) tertiary Syphilis. Syphilis inflames the vasa vasorum (called endarteritis obliterans). Thoracic aortic aneurysms may also occur with Marfan syndrome. Thoracic aneurysms are deadly. If the aneurysm is near the beginning of the aorta (the root), it can stretch out the annular ring (the base for the aortic valve), causing aortic regurgitation. An aneurysm of the arch can also compress the recurrent laryngeal nerve and cause hoarseness.

Abdominal Aortic Aneurysms (AAAs) are more common than thoracic ones. You should know the clinical presentation cold. It’s a unique set of symptoms, and it’s pathognomonic for a AAA. The patient (an old male smoker) will have a pulsatile abdominal mass. Small AAAs themselves aren’t very dangerous (although thromboemboli do like to form inside them). The real problem is that all AAAs will eventually rupture. AAA rupture is one of the most devastating conditions in all of medicine. The odds of surviving are negligible. Here are the symptoms. Left flank pain -- the aorta is a retroperitoneal structure, which is why the pain may involve the abdomen, back or (left) flank. Syncope / lightheadedness / hypotension -- blood pours into the retroperitoneal cavity, which eventually deprives the brain of oxygen. This is one of the few abdominal pathologies that causes syncope! AAA’s are common in older males with a 20+ pack-year smoking history, so they need to be screened once in their life with an abdominal ultrasound.

AORTIC DISSECTIONS

Wall splits

An Aortic Dissections is a pocket of blood within the wall of the Aorta. It’s an emergency. It causes severe tearing chest pain that radiates to their back (the Aorta is retroperitoneal). Here’s the difference between dissections and aneurysms:

Dissections occur when the intimal layer tears. The cause of the tear is usually long-standing hypertension (thus dissections only occur in the high-pressure aorta). The only other cause is a genetic connective tissue disease (e.g., Marfan's or Ehlers Danlos). Dissections will spread along the medial-intimal border if left untreated. Upper dissections (arch and ascending aorta) are more concerning than lower dissections (descending aorta). Dissections are dangerous. The risk of death rises 1% every hour. Type A dissections involve the Ascending Aorta or the Aortic Arch. Requires urgent surgical repair, because it can cause deadly complications involving the heart and aortic arch. Type B dissections only involve the descending aorta (Beyond the arch). Sometimes treated surgically, sometimes treated conservatively with medicine (esmolol to lower BP and heart rate) and close monitoring.

The gold standard for diagnosis is a chest CT with contrast, looking for a line within the aorta lumen. But you can sometimes spot them on a CXR, looking for mediastinal widening (60% sensitive for dissection). An even cheaper test is to look for asymmetry in the BP / pulses of their arms (30% sensitive, but pretty specific). In my experience, their BP is usually pretty high. And I recently read in a journal that the D-dimer is a 90% sensitive / specific test, but I don’t think that’ll be tested on boards.

You are expected to spot an Aortic Dissection on a chest CT.

Mediastinal Widening on a chest x-ray (Aortic Dissection)

The Aorta is very thick, which makes it hard to perfuse the walls. The vasa vasorum refers to "vessels of the vessels." It is the blood supply of any artery's walls. It provides perfusion from the vessel’s periphery. The Aorta is the largest artery in the body, meaning it requires the most robust vasa vasorum. Certain pathologies can disturb the Aorta's vasa vasorum, leading to weakness of the Aorta's walls.

ARTERIOLOSCLEROSIS

Thiccening of small arteries

Arteriolosclerosis is the thiccening or hardening of small vessel (arterioles) walls. It limits blood flow.

Arteriosclerosis (without the -olo-) is the thiccening of any artery’s walls. It also limits blood flow.

I personally find these to be incredibly confusing. Thankfully, you won’t be expected to know a TON about them. You have to (a) recognize histological pictures of hyaline & hyperplastic arteriolosclerosis, (b) associate Hyperplastic Arteriolosclerosis with Malignant Hypertension, and you might be expected to know (c) the pathophysiology / imaging / prognosis of Monckeberg Sclerosis (calcification / lead pipes / benign).

Hyaline Arteriolosclerosis

Pink goop around vessel

Hyperplastic Arteriolosclerosis

Onion skinning around vessel

Mönckeberg Sclerosis

Arteries light up on x-ray