Diseases Of Renal Vessels Flashcards
Layers of blood vessels
Innermost -> outermost
1) tunica intima
- endothelium and thin subendothelial layer of loose CT
- * in arteries only, intima includes thin layer of internal elastic lamina
2) tunica media
- lots of smooth muscle and elastic fibers
- * in arteries may also present with a external elastic lamina layer
3) tunica externa
- connective tissues with type 1 fiber as and elastic fibers
Nephrosclerosis
Associated with renal arterioles and small artery sclerosis
- causes glomerulosclerosis and chronic tubulointerstital injuries.
- vessels are narrowed lumens and focal parenchyma ischemia
**strongly associated with HTN and diabetes
***more common in blacks and advanced age
Pathogenesis of nephrosclerosis
Two processes
1) medial and intima thickening
- response to hemodynamic changes, aging, genetic defects
2) hyalinization of arteriolar walls
- response to leakage of plasma proteins through injured endothelium and increased basement membrane matrix
Malignant nephrosclerosis
Renal vascular disorder associated with malignant or accelerated HTN
Really only affects younger patients who are male and black
- usually also only develops as a superimposed condition on preexisting essential HTN and underlying chronic renal disease
**leads to rapid renal failure from untreated malignant HTN
Malignant nephrosclerosis pathology
Almost always the initial insult is some form of vascular damage to the kidneys
Leads to fibriunoid necrosis of arterioles and small arteries with activation of intravascular thrombosis
Can also cause hyperplastic arteriolosclerosis if mitogenic factors cause hyperplasia of intima smooth muscle of vessels
- typical in malignant HTN
What system is often chronically stimulated in malignant nephrosclerosis?
RAAS
- the kidney is markedly ischemic which in turn makes the kidney think the overall blood pressure and volume in the body is low all the time
this cycle further increases ischemia however since angiotensin-2 further vasoconstricts and renin further increases due to increased vasoconstriction
Fibrinoid necrosis vs hyperplastic arteriolosclerosis
Fibrinoid necrosis
- cytology detail is lost within the vessel and the vessel wall takes on a smudgy eosinophilic appearance (due to fibrin deposition)
- NO inflammation
Hyperplastic arteriolitis
- looks line an “onion-skin”
- can show inflammation
- more often leads to renal failure
Clincial features of malignant nephrosclerosis
BP is >200/120
Shows:
- papilledema
- retinal hemorrhages
- symptoms of encephalopathy
- cardiovascular abnormalities
- symptoms of early renal failure
- marked proteinuria and hematuria
Treatment = intense aggressive HTN treatment to prevent irreversible renal injuries
- before current HTN drugs mortality was 50-90%
- now mortality is 30-50%
Thrombotic microangiopathies (TMA)
Lesions in various clinical syndromes
Primary forms:
- Shiga toxin-HUS, TTP and atypical HUS (complement mediated TMA)
Secondary forms:
- Malignant HTN and scleroderma-associated TMA
Classic laboratory findings in TMAs
- Thrombocytopenia
- Hemolytic anemia (microangiopathic)
Caused due to chronic platelet consumption and shearing mechanical damage to RBCs as they pass through the clot site (respectively)
Shiga toxin mediated HUS pathogenesis
** msot common cause of TMA (75% of TMAs are started after GI infection of Shiga toxin E. Coli
E. Coli Shiga toxin producing species causes HUS due to the Shiga toxin itself
Toxin causes endothelial damage and glomerular endothelial cell damage
- toxin activated increased endothelin and decreases nitric oxide production (both together promotes vasoconstriction and both platelet adhesion and activation)
- high does = cell death
**also produces thrombi sometimes which often get stuck in afferent arterioles of the kidney
Atypical HUS pathogenesis
Usually hereditary causes that dampen complement activation via the alternative pathway
- leads to excessive activation of complement and ensuing microvascular injury and microvascular thrombosis
- also activated MAC (target for therapeutic antibody action)
no diarrhea
(Thrombotic Thrombocytopenic Purpura) TTP pathogenesis
Inherited deficiencies of ADAMTS13 (plasma protease that cleaves vWF)
- inherited = mutations in the ADAMTS13 gene
- acquired = antibodies against ADAMTS13 gene
both result in formation of abnormally large vWF multimers that activate platelets spontaneously and formation of thrombosis
Shiga toxin associated HUS symptoms
Sudden onset of hematemesis, melena hematuria and severe oligouria.
- **almost always proceeds after a GI or flulike prodromal episode
- anemia and neurological changes are also seen
is a main cause of AKI in children and most recover within weeks. However there is a 25% chance of developing renal insufficiency in 25 yrs
Atypical HUS symptoms
Similar to Shiga toxin except there is **NO prodromal flu-like or GI infection
Treatment requires antibody inhibitors, plasmapheresis or liver transplant to cure
(so more aggressive and without this, usually provides a poorer outcome)
