4 Vascular disease/CKD

Question 1

What is hypertensive nephrosclerosis?

Answer 1

• chronic kidney disease (scarring!) in a patient with long-standing, poorly controlled HTN
• typically evidence of other end organ damage as well
• proteinuria often present (many filters scarred, so the remaining ones become stressed and “leaky”)

Question 2

What are the gross morphologic features of hypertensive nephrosclerosis?

Answer 2

• normal to slightly small kidney
• finely granular subcapsular surface

Question 3

What are the histological findings of hypertensive nephrosclerosis?

Answer 3

• subcapsular glomerular sclerosis
• arteriolar hyaline
• “downstream damage” from glomerular sclerosis:
  
  • tubular atrophy
  • interstitial fibrosis

Question 4

What are the histologic findings in the kidney caused by malignant HTN?

Answer 4

• mucoid intimal thickening (arteries)
• glomerular capillary wrinkling (afferent constriction, kidney trying to protect itself from high pressures)
• glomerular basement membrane duplication (similar to thrombotic microangiopathy)

Question 5

What causes renovascular HTN?

Answer 5

• renal artery stenosis from…
  
  • atherosclerosis (in older patients)
  • fibromuscular dysplasia (especially in young females)
  • trauma, dissection, extrinsic compression/tumor
• decreased blood flow to the kidneys causes secondary HTN

Question 6

What is the mechanism of renovascular HTN?

Answer 6

• decreased renal blood flow releases renin
• renin converts angiotensinogen to angiotensin I
• ACE converts ang I to ang II
• ang II vasoconstricts and stimulates aldosterone release
• aldosterone increases Na/water reabsorption

Question 7

When should you suspect renal artery stenosis?

Answer 7

• early or late onset HTN (outside the range of 20-60 yo)
• difficult to control HTN
• abdominal or flank bruit
• renal failure after starting ACE inhibitor
  
  • efferent arteriole dilation unmasks dysfunction

Question 8

What are the morphologic features of renal artery stenosis caused by atherosclerosis?

Answer 8

• stenosis in the proximal renal artery
• eccentric plaque with intimal fibrosis, cell debris, lipid and foam cells
• medial and adventitial fibrosis
• plaque may hemorrhage/dissect
• calcification may occur

Question 9

What are the morphologic features of renal artery stenosis caused by FMD?

Answer 9

FMD= fibromuscular dysplasia (intimal, medial, and adventitial forms)

• alternating thinned media and thickened fibromuscular ridges
  
  • forms “string of beads” radiographically
  • beading is larger than caliber of artery
• middle to distal artery

Question 10

What are the arteries commonly affected by FMD?

Answer 10

FMD= fibromuscular dysplasia

• renal artery (60-75%, bilateral 35%)
• cervicocranial arteries (25-30%)
• visceral arteries (9%)
• extremity arteries (5%)

**two vascular beds involved in up to 28%

Question 11

What are the treatments for renal artery stenosis?

Answer 11

• medical management only (common)
• surgical revascularization (only if severe)
• angioplasty and stenting

Question 12

What are the morphologic features of a renal cortical infarct?

Answer 12

• renal artery occlusion -> extensive parenchymal infarction
• smaller branch -> wedge-shaped infarct
  
  • pale with hyperemic border
  • coagulative necrosis
  • hemorrhage and acute inflammation at edge
• fibrotic (later)

Question 13

Describe atheroembolic disease

Answer 13

• Disruption of atherosclerotic plaques (aka “a kidney heart attack”)
• Can cause acute and subacute renal failure
• Eosinophils can be seen in the blood or urine (may be related to activation of C5a)
• Occurs after procedures that disrupt plaques in the aorta, leading to a shower of cholesterol emboli that lodge in the renal microvasculature

Question 14

What are the outcomes of atheroembolic disease?

Answer 14

• stabilized or normal renal function in mild, isolated cases
• chronic, progressive deterioration in renal function in subacute cases
• end-stage renal disease in severe cases
  
  • permanent dialysis may be necessary

Question 15

What is TMA?

Answer 15

TMA= thrombotic microangiopathy

• characterized by thrombosis in capillaries and arterioles
  
  • microangiopathic hemolytic anemia (MAHA)
  • thrombocytopenia
  • renal failure
• e.g. hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP)

Question 16

What is the pathogenesis of TMA?

Answer 16

TMA=thrombotic microangiopathy

• endothelial injury and activation
  
  • intravascular thrombosis
• platelet aggregation
  
  • vascular obstruction
  • vasoconstriction
• “small blood vessels taking a beating” -> disrupts flow -> increases clotting -> RBCs lyse

Question 17

What is HUS?

Answer 17

HUS= hemolytic uremic syndrome

• commonly from shiga toxins
• often occurs after intestinal infection with E coli O157:H7

Question 18

Define chronic kidney disease

Answer 18

• progressive irreversible renal insufficiency that develops over months to years
• may ultimately lead to end-stage renal disease (GFR <10 ml/min)

Question 19

What are the main causes of chronic kidney disease?

Answer 19

• diabetes (irreversible; “caterpillar on a leaf” analogy)
• hypertension
• glomerulonephritis
• cystic diseases

Question 20

How is the kidney size affected in chronic kidney disease?

Answer 20

• usually (but not always) reduced kidney size
• may have normal or large kidneys in…
  
  • diabetes
  • amyloidosis
  • HIV
  • cystic kidney disease

Question 21

What are the 3 main consequences of CKD?

Answer 21

CKD= chronic kidney disease

1. anemia
   
   • decreased erythropoietin production (because of decreased function of fibroblasts at the cortico-medullary junction)
   • occurs below GFR of 60 ml/min
2. hypertension (increased renin)
3. secondary hyperparathyroidism

Question 22

Describe the complications of secondary hyperparathyroidism in CKD

Answer 22

• decreased renal synthesis of 1,25 dihydroxy vitamin D3 and decreased phosphate excretion result in…
  
  • hypocalcemia
  • hyperphosphatemia
  • renal osteodystrophy

Question 23

What are some other possible findings in CKD?

Answer 23

• metabolic acidosis
  
  • decreased secretion of ammonium and retention of phosphates/sulfates
• hyperkalemia (K excretion increased via GI)
• inability to maintain sodium and water balance
• coagulopathy- platelet dysfunction
• sensorimotor neuropathy

Question 24

What are the physical symptoms of CKD?

Answer 24

Physical symptoms of chronic uremia:

• lethargy, fatigue
• day-night sleep reversal
• anorexia, N/V
• pruritus
• restless legs syndrome
• uremic percarditis

Question 25

How can you slow the progression of CKD?

Answer 25

• control hypertension (ACEi, ARB)
• reduce proteinuria (slows “holes in the filter”; tubules are injured by protein)
• control blood sugar and hyperlipidemia
• smoking cessation
• disease-specific therapy as indicated (anemia, acidosis)
• dietary restrictions
  
  • Na, K, phosphorus, protein?

Question 26

What is the most common cause of CKD and end-stage renal disease in the US?

Answer 26

diabetes

Question 27

How do you treat ESRD?

Answer 27

• ESRD= end-stage renal disease
• treat with…
  
  • dialysis
  • kidney transplant