B74 vascular diseases of the kidney

Question 1

What are the vascular diseases discussed specifically in the kidney chapter?

Answer 1

Arteriolonephrosclerosis, Malignant hypertension, HUS, and TTP.

Question 2

Describe arteriolonephrosclerosis.

Answer 2

Arteriolonephrosclerosis:

Arterionephrosclerosis - the term used for the thickening and sclerosis of arterial walls and the renal changes associated with benign hypertension. Also called benign nephrosclerosis.

Hyaline arteriolosclerosis of the small arterioles.

Reduplication of the internal elastic membrane

Fibroelastic hyperplasia of the media. Thickening of the media due to fibrous deposition and hyperplasia of the cells.

Question 3

Describe malignant hypertension

Answer 3

Blood pressure above 200/120 mmhG

Arises de novo in normotensive patients, or may occur in patients with pre-existing mild/benign hypertension.

Cause:

• Injury to small vessel walls
• Increased permeability
• Fibrinoid necrosis and intravascular thrombosis
• Subsequently, platelet mitogenic factors cause intimal hyperplasia** and **hyperplastic arteriolosclerosis, forming onion-skin lesions around the small vessels.

Kidneys become ischemic, RAS system activated, further perpetuating renal ischemia, and hypertension.

Clinical symptoms

• Extremely high blood pressure 200/120
• First symptoms are from elevated intracranial pressure and increased filtration pressure in the glomerulus
• Headache, nausea, vomiting, and visual impairments black spots or scotomas.
• The extreme pressure also causes proteinuria and hematuria, but renal function is still in tact.
• Soon the RAS activation and renal ischemia causes acute kidney injury and renal function declines. Without intervention irreversible kidney ischemia will occur.

Malignant hypertension has a bad prognosis, with about 50% survival over 5 years.

90% of deaths are from kidney failure

10% from cerebral hemorrhage or heart failure.

Question 4

What are the thrombotic microangiopathies?

Answer 4

• Hemolytic uremic syndrome
• Thrombotic thrombocytopenic purpura (TTP)
• Various drugs
• Malignant hypertension or scleroderma

Question 5

Describe HUS

Answer 5

Mostly caused by strain O157:H7 of EHEC, which produces shiga toxin, and also by Shigella dysenteriae itself.

Shiga toxin is toxic to GI epithelial cells as well as Glomerular endothelial cells. Damage is most severe in glomerular capillaries, afferent arterioles, and interlobular arteries.

Causes thrombotic microangiopathy (thrombosis of the small vessels and resulting ischemia)

Also sometimes occurs in people with a mutation of factor H which inhibits complement activation. Minor endothelial injury causes excessive complement activation and damage initiating the thrombotic microangiopathy.

Clinical HUS:

• Sudden onset after GI infection with bloody diarrhea.
• Sudden, severe oliguria, hematuria, microangiopathic hemolytic anemia.
• Sometimes involves neurological defecits from microinfarcts
• The acute kidney injury needs to be treated with dialysis, and patients spontaneously recover over a couple weeks.
• However about 25% will develop renal insufficiency from secondary scarring

Question 6

Describe Thrombotic THrombocytopenic Purpura

Answer 6

Caused by an acquired defect in cleaving vWF. Usually from autoantibodies against ADAMTS 13 protease. Normally cleaves vWF multimers into smaller sizes.

The excessive concentration of very large vWF causes spontaneous platelet activation and thrombosis.

Inherited mutations to ADAMTS 13 can also cause a similar disease.

TTP has more prominent involvement of the CNS than HUS, and kidney problems are not as severe.