Pathology of Systemic Hypertension

Question 1

What are the two mechanisms by which angiotensin II raises blood pressure?

Answer 1

1. Direct contraction of arteriolar smooth muscle, increasing total peripheral resistance
2. Promoting adrenal release of aldosterone -> increases sodium resorption in distal convoluted tubule

Question 2

What are the two most common causes of renal artery stenosis?

Answer 2

1. Atherosclerosis with or without superimposed thrombosis, often at origin of renal artery
2. Fibromuscular dysplasia - often in young females

Question 3

What is fibromuscular dysplasia?

Answer 3

FIbromuscular thickening of layers of arterial wall, especially the media

-> tends to affect the renal artery

Question 4

If you have unilateral renal artery stenosis, what tends to happen in the ipsilateral vs contralateral kidney on a pathological level?

Answer 4

Ipsilateral - diffuse ischemic changes, including interstitial fibrosis and tubular atrophy

Contralateral - significant arteriolosclerosis (usually hyaline) dependent on degree of hypertension

Question 5

What is the main clinical finding which will be expected in renal artery stenosis?

Answer 5

Increased plasma renin levels, with possible ability to auscultate a bruit in the affected renal artery

Question 6

What is atherosclerosis vs arteriolosclerosis?

Answer 6

Atherosclerosis - macrovascular disease, narrowing of large arteries

Arteriolosclerosis - microvascular disease affecting arterioles and small muscular arteries

Question 7

What is the most common type of arteriolosclerosis and its pathophysiology?

Answer 7

Hyaline arteriolosclerosis, due to benign hypertension or diabetes

• > wall thickening due to leakage of plasma proteins and ECM synthesis from progressive endothelial damage.
• > progressive luminal narrowing

Question 8

What is the second type of arteriolosclerosis and what is its pathogenesis?

Answer 8

Hyperplastic arteriolosclerosis, appears with fibrinoid necrosis in severe malignant hypertension -> diastolic BP >120 mmHG.

Vessels are injured -> plasma proteins leak out and thrombosis occurs -> PDGF leads to intimal hyperplasia, decreasing perfusion due to vasoconstriction.

Vasoconstriction decreases perfusion to renal artery, leading to worsening hypertension via RAA and further hyperplasia.

Question 9

What can be seen pathologically in hyerplastic arteriolosclerosis? Grossly in kidney?

Answer 9

Concentric proliferation of myofibroblastic cells “onion-skin” apperance

Accompanied by fibrinoid necrosis and petechial hemorrhages.

Grossly: Kidney will have a flea-bitten appearance due to hemorrhages on cortical surface

Question 10

What tends to happen to blood vessels in the brain in severe hypertension? What are these called?

Answer 10

Hyaline / hyperplastic arteriolosclerosis, as well as formation of microaneurysms due to weakening of media called Charcot-Bouchard microaneurysms

Aneurysms are susceptible to rupture, causing deep CNS hemorrhage

Question 11

What areas of the brain are most susceptible to microaneurysm rupture in systemic hypertension?

Answer 11

Putamen (BG), thalamus, and pons

Question 12

What pathologic process occurs in the kidneys due to longstanding essential hypertension and diabetes mellitus? How does this appear grossly? Clinical result?

Answer 12

Benign nephrosclerosis

Grossly: Small or normal-sized kidneys with a finely granular cortical surface

Clinical result: Decreased renal blood flow but only a small reduction in GFR

Question 13

How does benign nephrosclerosis appear microscopically in larger arteries?

Answer 13

Larger arteries - interlobular and arcuate

Fibroelastic hyperplasia -> myofibroblast hyperplasia, reduplication of elastic lamina, medial smooth muscle hypertrophy, and luminal narrowing (large arteries respond somewhat like hyperplastic arteriolosclerosis)

Question 14

How does benign nephrosclerosis appear microscopically in small arteries / arterioles and renal parenchyma?

Answer 14

Small arteries / arterioles - hyaline arteriolosclerosis

Renal parenchyma - ischemic changes - interstitial / glomerular fibrosis and accompanying tubular atrophy

Question 15

What are the microscopic features of malignant nephrosclerosis? (Grossly = flea-bitten appearance)

Answer 15

Small arteries / arterioles -> hyplastic arteriolosclerosis with fibrinoid necrosis

Renal parenchyma -> infarction and/or ischemic atrophy (if you had prior benign hypertension)

Question 16

What other clinical findings will be associated with malignant hypertension which causes malignant nephrosclerosis?

Answer 16

Increased systemic blood pressure, ICP (papilledema / encephalopathy), cardiac complications, and renal abnormalities including proteinuria, hematuria, and acute renal failure

Question 17

What retinal changes of hyaline arteriolosclerosis can be seen very early on?

Answer 17

1. Narrowing / tortuosity of retinal arteries
2. Copper-wire / silver-wire appearance -> due to thickened wall and narrowed blood column, altering light reflex
3. AV nicking

Question 18

What is AV nicking and why does it occur?

Answer 18

Venous compression (typically the larger vessel in the pair) by a thick artery crossing over it due to them both sharing the same connective tissue sheath and the artery having undergone hyaline arteriolosclerosis

Question 19

As vascular walls weaken, forming microaneurysms and hemorrhages in the retina, how do you know if a hemorrhage is superficial vs deep?

Answer 19

Flame-shaped hemorrhages - more superficial, as the nerve fiber layer runs perpendicular to the rods and cones in the back of the retina, and the hemorrhage follows these.
(we are seeing their long axis).

Dot hemorrhages - more deep, as the hemorrhage runs between the plexiform layers which are parallel to the rods / cods in the retina.(we are seeing their short axis)

Question 20

What causes cotton wool spots? What do they look like?

Answer 20

Severe ischemia and infarct in the nerve fiber layer (innermost layer, closest to vitreous) which results in swollen, damaged, distal axons due to disruption of axonal transport. These are “cytoid bodies”

-> look like fluffy, white lesions of the inner retina

Question 21

How serious are hard exudates in the retina and what are they?

Answer 21

Very serious -> represent a severe, acute increase in blood pressure which has resulted in the breakdown of the blood-retinal barrier

-> leakage of lipid and protein into the retina, causing small, yellow, oval lesions deep in the retina

Question 22

What are the most severe findings of malignant hypertension in the retina? Will vision changes occur?

Answer 22

Optic disc swelling (papilledema), associated with macular star

-> macular star due to how nerve fibers are arranged around the fovea, and complete loss of outer blood-retinal barrier causing many hard exudates to deposit around.

Papilledema due to very high ICP.

-> this is where we will see blurred vision typically