Atherosclerosis is a primary factor for certain dz’s –

CAD; atherosclerotic stroke relates to plaques; abdominal aneurysm due to weakening of the vessel;

nontraumatic amputation of lower extremity (peripheral vascular dz); mesenteric angina, small bowel infarction, renovascular atherosclerosis of the renal arteries. Atherosclerosis only involves muscular arteries and elastic arteries. Can small vessel, such as arterioles get hardened? Yes. Example: look at the spleen – hyaline arteriolar sclerosis and hyperplastic arteriolar sclerosis (onion skinning).

1. Hyaline arteriosclerosis is a small vessel dz; lumen is narrow; whenever there is a lot of pink staining stuff, this is hyaline. Example: small vessel dz of diabetes and HTN – two major dz’s that produces a small vessel dz with different mechanisms:

a. Diabetes: nonenzymatic glycoslyzation – aka HbA1c; glycoslyzation is glucose attaching to aa and protein. For HbA, its glucose attaching to aa and HbA, and the HbA is glycosylated. HbA1c levels correlate with the blood glucose levels of the last 6-8 weeks, so this is the best way of looking at long term glucose levels. All the damage seen in diabetes is due to glucose. For a diabetic, you should be under 6%, meaning that you are in a normal glucose range. There is nothing unique about diabetes except for a large glucose level, you keep that normal, and it’s as if you don’t have diabetes. The only two pathologic processes are this: nonenzymatic glycosylation of small BV’s including capillaries in the kidney, and osmotic damage. Those tissues that contain aldose reductase – lens, pericytes in the retina, schwann cells – all have aldose reductase and can convert glucose into sorbitol and sorbitol is osmotically active sucks water into it and those cells die, leading

to cataracts, microaneurysms in the eye b/c the pericytes are destroyed and weakened and the retinal vessels get aneurysms, and you get peripheral neuropathy b/c schwann cells are destroyed.

They all related to excess glucose. So, tight glucose control = normal life.

What does nonenzymatic glycosylation to do the basement membrane of small vessels? Its renders them permeable to protein, so the protein in the plasma leaks through the BM and goes into the vessel wall, produces a hyaline change and narrows the lumen. What if there is nonenzymatic glycosylation of the GBM? It will render it permeable to protein – called microalbuminuria. This is the first change to be seen in diabetic nephropathy. So, what is the mechanism? Nonenzymatic glycosylation.

b. Hypertension

Does not use nonenzymatic glycosylation. It just uses bruit force and drives (b/c of increase in diastolic pressure) the proteins through the BM and produces the effect. When we look at a kidney in HTN, it is shrunken, has a cobblestone appearance – this is b/c there is hyaline arteriolosclerosis of the arterioles in the cortex, ischemia, and is wasting away with fibrosis and atrophy of tissue.

Lacunaer strokes (tiny areas of infarction that occur in the internal capsule) are a hyaline arteriosclerosis problem related to HTN.

2. Hyperplastic arteriosclerosis

Seen in malignant HTN; more common in blacks then whites, mainly b/c HTN is more common in blacks than whites. Mainly see this vessel dz in malignant HTN (ie when pt has BP of 240/160).

B. Aneurysm

1. Definition: area of outpouching of a vessel due to weakening of the vessel wall.

Atherosclerosis can cause weakening of the abdominal aorta leading to an aneurysm.

What would be the analogous lesion in the lungs with weakening and outpouching? Bronchiectasis – due to cystic fibrosis with infection, destruction of elastic tissue leading to outpouching and

dilatation of the bronchi. Example: what is the GI aneurysm? Diverticular dz – have a weakening and outpouching of mucosa and submucosa

2. Law of Laplace – the wall stress increases as radius increases. In terms of this, once you start dilating it, it doesn’t stop b/c as you dilate something, you increase the wall stress and eventually it ruptures. So, in other words, all aneurysms will rupture – it’s just a matter of when.

3. Abdominal Aorta Aneurysm: Why is the abdominal aorta the MC area of aneurysm? B/c there is no vasa vasorum or blood supply to the aorta below the renal arteries. So, the only way abd.

aorta gets O2 and nutrients is from the blood that’s in the lumen. So, part furthest from it mgets screwed. Therefore, apart from the part that is not getting much O2 and nutrients, it will be more susceptible to injury, therefore atherosclerosis leads to weakening of the wall and aneurysm/injury occurs.

a. MC complication abdominal aortic aneurysm = rupture. The triad of s/s are: a sudden onset of severe left flank pain b/c the aorta is retroperitoneal organ and so it does not bleed into the peritoneal cavity, but into the peritoneal tissue. So, severe left flank pain, HypoTN, and pulsatile mass on PE. These are three things that always occur when there is a ruptured aortic abdominal aneurysm. MC complication of any aneurysm = rupture

4. Aneurysm of the arch of the aorta – MCC = tertiary syphilis. Pathology of syphilis is vasculitis of arterioles. Chancre, too. Its painless b/c if you section it, you will see little arterioles surrounded by plasma cells and the lumen of the vessel is completely shut, so it is ischemic

necrosis. In other words, it is ischemia of the overlying tissue undergoing necrosis. B/c nerves are next to vessels, they are knocked off, too, and it is painless. All of syphilis is a vasculitis. That is what the Treponema infects – small vessels and arterioles. What are they affecting in the arch of the aorta? The vasa vasorum; the richest supply of vasa vasorum is in the arch, so its logical that the Treponema will pick it – leads to endarteritis obliterans (they are obliterating the lumen), ischemia, weakening under systolic pressures, leads to depression in the arch of the aorta (looks like a catcher’s mitt). What will that do to the aortic valve ring? It will stretch it – which murmur will this lead to? Aortic regurg. Murmurs can occur b/c there is valvular damage or b/c the valvular ring is stretched. So, there can be stretching of the ring and nothing wrong with the valves, and have a murmur, or you can have damage to the valves and have a murmur. Syphilis is an example of stretching of the aortic valve ring leading to a murmur and aortic regurg.

Aorta should be closing during diastole – as you pump the blood out, and the SV goes down, and b/c the aortic cannot close properly, only some of the blood will drip back in. So you will have more volume of blood in the left ventricle in someone with aortic regurg. Frank-starling forces will be working. As you stretch cardiac muscle, you increase the force of contraction. Normally, you have a 120 ml’s of blood and get out 80, so the EF is 80/120 =66%. Lets say you have 200 mls of blood in the LV b/c blood is dripping back in, and frank-starling force gets out 100 mls of blood, which has an EF of 50%. So this isn’t as efficient. Therefore, frank-starling occurs in a pathologic condition. If you have 100 mls of blood coming out of your aorta, that’s not good b/c their head is wobbling, and when they open their mouth you can see uvula pulsating, can take their nail and lift it up and see pulsations of the vessels under the nail, Water-hammer pulse, and when listening with the

stethoscope of the femoral artery you can hear Durasane’s sign. This is all due to the increase in SV coming out related to the fact that there is more blood in the LV. syphilitic aneurysms of the

abdominal aorta is the classic example of this. Anatomy correlation: the Left Recurrent Laryngeal Nerve wraps around the arch and therefore can get hoarseness. Again the MC complication is rupture.

5. Dissecting aortic aneurysm:

a. Key factor that causes a tear in the aorta is HTN b/c it imposes stress on the wall of the vessel. There must be weakening the elastic artery and is caused by elastic tissue fragmentation.

Cystic medial necrosis: that’s where the GAG’s mix together and there’s mucinous material w/in, and walls of aorta rub upon itself, and when adding a little bit of HTN leads to a tear. Wherever the area of weakness in the elastic artery is where the blood will dissect and tear – blood can go to the pericardial sac, leading to cardiac tamponade. This is called the proximal dissection (MC). Most of the tears up in the arch; therefore you would think the pt may have an absent pulse; this is very common in pts with tears that are proximal. When it dissects, it closes lumen to subclavian artery and it usually dissects on the left and causes an absent pulse on left.

b. Chest pain in MI is diff than the chest pain in a dissecting aneurysm. MI has chest tightness radiating to left arm and jaw; in aortic dissection, there is a tearing pain radiates to the back; and is a retrosternal pain. Pulse on left is diminished vs. the one on the right. On chest x-ray, widening of the aortic knob. With blood there, diameter of aorta will be enlarged, as seen on x-ray, and this test is 85% sensitive in detecting it, therefore it is the screening test of choice; see widening of the proximal aortic knob. To prove, do transesophageal ultrasound or angiography to confirm dx.

c. Many dz’s can predispose to aortic dissections:

(1) Marfan syndrome (eunochoid proportions – ht of pelvic brim to feet is greater than from pelvic brim to the head. Also, another definition is that arm span is greater than the height. AD inheritance, c’some 15, defect in fibrillin, which is a component in elastic tissue. Due to the defect in fibrillin, the elastic tissue is weak – this is why they have dislocated lenses and have dissected aortic aneurysms (MCC death in marfans is MVP).

(2) Ehler Danlos has a collagen defect, MCC of death

(3) Pregnant women are susceptible to dissecting aortic aneurysms b/c in pregnancy they have twice the amount of plasma vol vs. a non-pregnant woman. There is an increase of plasma vol by 2 and RBC mass by 1, so it’s a 2:1 ratio of increasing plasma vol to RBC mass; which decreases the Hb concentration. That’s why all pregnant women have decreased hemoglobin; usually around 11.5 is their cutoff for anemia and the cutoff is 12.5 for normal women. This is b/c of dilutional effect with excess in plasma vol. Apparently in some women, the excess plasma volume for 9 months can cause weakening of the aorta and thereby causing an aneurysm.

V. Venous Disorders:

A. Superior vena cava lung syndrome in a smoker with primary lung cancer, now complaining