Chapter 20.3 Vascular Diseases Flashcards
Renal vascular diseases can be categorized in what ways?
- Small vessel disease
- Large vessel disease
- Thrombotic microangiopathies
- Other
Nephrosclerosis, commonly assx with _____, is defined by prescense of varying degrees of
Nephrosclerosis, commonly assx with HTN, is defined by prescene of varying degrees of
- glomerulsclerosis
- interstitial fibrosis and tubular atrophy
- arteriosclerosis
- arteriolosclerosis
In nephrosclerosis, what happens as the lumen narrows?
- contributes to glomerulosclerosis (global and segmental), which can cause interstitial fibrosis and tubular atrophy.
What is Benign Nephrosclerosis.
- Hyaline sclerosis of the renal arterioles and small arteries d/t benign HTN=> multi-focal ischemia of kidney parenchyma that the sclerotic vessels supply
Is Benign Nephrosclerosis is a general process or a specific Dx?
General process
Benign Nephrosclerosis is strongly associated with _________
and it will occur more in who?
- HTN
- Blacks, increasing age and DM
What 2 microscopic processes occur in benign nephrosclerosis?
- Medial and intimal thickening (fibroelastic hyperplasia) due to hemodynamic changes, aging => narrowing of lumen
- Hyaline protein depositions in arteriolar walls (hyaline arteriolosclerosis) => homogenous and eosinophillic thickening
How does the cortical surface of the kidney appear in Benign Nephrosclerosis?
- Granular, leather appearance due to scarring and shrinking => causing a reduction in cortical mass
Ischemia that occurs in Benign Nephrosclerosis causes what?
- patchy ischemic atrophy of tubules and glomeruli
Benign nephrosclerosis can progress to what?
- glomerulosclerosis
- chronic tubulointerstitial injury (tubular atrophy & interstitial fibrosis)
Does Benign nephrosclerosis cause renal failure/renal insufficiecy.
No. Obny in 3 cases:
- African-Americans
- Severe HTN
- Diabetic Nephropathy
Malignant Nephrosclerosis typically occurs most often in whom?
Younger men, black
- Malignant Nephrosclerosis is a renal disease with typical arterial changes associated with ______________
Malignant or accelerated HTN
What type of HTN is a clinical syndrome and a medical emergency?
Malignant HTN
What is the pathogenesis of malignant HTN?
- Injured endothelium (d/t hemodynamic changes) => ↑ permeability to fibrinogen and plasma proteins,
- => Irreversible endothelial injury => focal vascular cell death and platelet deposition
- This will lead to:
- fibrinoid necrosis of arterioles and small arteries,
- activation of platelets and coagulation factors causing intravascular hemorrhage** and **thombosis
- Fibrinoid necrosis leads to hyperplastic arteriolitis/onion skinning (malignant arteriolar sclerosis), causes
- Ischemic kidneys d/t lumen narrowing.
- RAAS => Elevated plasma renin
- This creates a self-perpetuating cycle of damage and HTN
What do we see as a result of the fibrinoid necrosis and hyaline arteriolitis seen in malignant nephrosclerosis?
Ischemic kidneys and high plasma renin
- Lumen narrowing causes ischemic kidneys
-
+ RAASs ==> high plasma renin
*
High plasma renin results in what in Malignant Nephrosclerosis?
self-perpetuating cycle of damage and HTN
What are the morphological manifestations of malignant HTN.
Malignant arteriolosclerosis/malignant nephrosclerosis
How does the cortical surface of the kidney appear in Malignant Nephrosclerosis?
“Flea-bitten”; small, pinpoint petechial hemorrhages
What are the histological manifestation of malignant nephrosclerosis?
- Fibrinoid necrosis of arterioles
- Hyperplastic arteriolitis (collagen + proteoglycans and plasma proteins), indicative of renal failure
The full-blown syndrome of Malignant HTN is characterized by what BP, and other serious clinical manifestations?
- BP: >180/>120,
- Papilledema,
- Retinal hemorrhages,
- Encephalopathy
- CV abnormalities
- Renal failure
Early symptoms of Malignant HTN are due to what?
↑ ICP
Large vessel disease: Unilateral renal artery stenosis causes ____________ and is important to recognize. Why?
- Unilateral renal artery stenosis causes 2-5% of HTN cases and is important to recognize because it is curable by surgery.
Renal artery stenosis is a cause of _____ due to what?
HTN
Due to an increasing production of renin from an ischemic kidney
What perpetuates HTN in renal artery stenosis?
Accumulation of Na+
Renal artery stenosis is most commonly due to what?
1. Atherosclerosis (70%)
2. Fibromuscular dysplasia (medial** (most common), intimal and adventitial hyperplasia)
Atherosclerosis is more common in
- Men
- Increasing age
- DM
Which cause of renal artery stenosis is more often seen in younger age groups (3rd-4th decades) and is more common in woman?
Fibromuscular dysplasia of the renal artery
Which cause of renal artery stenosis is more often seen in older people?
atherosclerosis;
What is the classic appearance on arteriography of renal artery stenosis due to fibromuscular dysplasia?
“String of beads”
In general pts w/ renal artery stenosis present clinically similar to what other disorder?
How can it be diagnosed?
- Resemble those w/ essential HTN
- Occasionally bruit can be heard over kidney on ausculation (rare)
- High renin levels, response to ACE inhibitors, renal scans, and IV pyelography may all aid in Dx
- Need arteriography to localize stenotic lesion
What is the arteriolosclerosis like in the ischemic kidney in renal artery stenosis vs. non-ischemic (functional) kidney?
- Ischemic kidney: decrease size and show signs of diffuse ischemic necrosis
- Contralateral kidney (healthy) may show more severe arteriolosclerosis, depending on severity of the HTN!
*Think the ischemic kidney w/ stenosis is essentially shut off from the blood supply, while the functional kidney is getting rocked by extremely high/persistent BP
What are the 2 important thrombotic microangiopathies?
- HUS (Hemolytic-uremic syndrome)
- TTP (thrombotic thrombocytopenic purpura)
Thrombotic microangiopathy are a diverse set of conditions that all lead to
- Insults that cause excessive activation of platelets, forming thrombi in capillaries and arterioles in various tissue beds, including the kidneys.
What are the 3 major findings in the Thrombotic Microangiopathies (HUS and TTP)?
- Thrombi in capillaries and arterioles
- Microangiopathic hemolytic anemia
- Thrombocytopenia (low platelet count)**** (big clue in a question stem!)
Thrombocytopenia that occurs in HUS and TTP causes what?
- Results in flow abnormalities that shear red cells
- Causes microangiopathic hemolytic anemia and microvascular occlusions
- Causes ischemia and organ dysfunction.
The primary cause/inciting event that causes thrombi formation in HUS differs from TTP how as far as pathogenesis?
- HUS = injury to endothelial cells and platelet activation ==> intravascular thrombosis
- TTP = platelet activation –> aggregation
What are triggers of injury to endothelial cells?
- bacterial toxins
- cytokines
- viruses
- certain meds
- anti-endothelial antibodies
In HUS, what is a result of damage to the endothelial cells?
- Decrease prostaglandin I2 and NO, which inhibit aggregation of platelets
- Increased endothelin, which causes vasoconstriction
What is the trigger for platelet activation and thrombosis in typical HUS vs. atypical HUS?
- Typical HUS - Shiga-like toxin (from E.coli) after eating food
- Atypical HUS - inherited mutation of proteins that cause excessive activation of complement
Typical HUS is associated with what synonyms?
1. Epidemic
2. Classic
3. Diarrhea +
Atypical HUS is associated with what synonyms?
- Non-epidemic
- Diarrhea negative
Who is most often affected by Typical HUS?
How is this form treated/managed and prognosis?
- Children
- Renal failure is managed w/ dialysis and most pts recover normal renal function within weeks
- Long-term prognosis is variable due to renal damage
What are the 2 common inherited mutations which cause Atypical HUS?
- factor H mutation
- Factor I and CD46 mutation
Besides inherited mutations, what else can cause Atypical HUS?
- Antiphospholipid syndrome, either 1° or 2° to SLE
- Pregnancy –> postpartum renal failure
- Vascular diseases of kidney: systemic sclerosis and malignant HTN
- Chemotherapy and immunosupprants
- Irradiation of kidney
What has a worse prognosis: Typical or Atypical HUS?
Atypical, due to underlying conditions
Thrombotic Thrombocytopenic Purpura (TTP) is classically manifested by what pentad, what is the dominant feature?
1) Neurological sx’s = Dominant feature
2) Fever
3) Microangiopathic hemolytic anemia
4) Thrombocytopenia
5) Renal failure
TTP and Atypical HUS both appear more commonly in adults, occassionally having similar sx’s. How are they distinguished from one another?
Atypical has of normal ADAMTS13 in plasma
TTP is associated with inherited or acquired deficiencies in what?
The most common cause is due to what?
- ADAMTS13 = negative regulator of vWF, which forms large multimers of vWF => activate platelets
- Inhibitory autoantibodies against ADAMTS13 = MOST COMMON!
Who is most often affected by TTP and it typically presents before what age?
- Woman
- Presents before 40 yo
What is the course of TTP and treatment?
- Relapsing and remitting course
- Plasma exchange to remove autoAB to ADAMTS13
Light microscopy of chronicdisease associated with atypical HUS/TTP will show what?
- Mildy HYPERcellular glomeruli
- Thickened capillary walls
- Splitting/reduplication of BM (“tram-tracks”)
- “Onion-skinning” of arterial walls
What are the morphological characteristics seen on micrcoscopy in both HUS/TTP?
Which arteries will show necrosis? (quiz question!)
- In acute, active dz, the kidney shows patchy or diffuse CORTICAL necrosis and subscapular petechiae
- Thrombi occluded glomerular capillaries
- Mesangiolysis
- Interlobular arteries w/ fibrinoid necrosis of wall and occlusive thrombi
When is life stress related to atherosclerosis?
When pt has unhealthy coping mechanisms
Bilateral renal artery disease (aka atherosclerotic ischemic renal disease) is a common cause of what in older individuals?
Chronic ischemia w/ renal insufficiency, sometimes w/o HTN
How is bilateral renal artery disease definitively diagnosed?
Treatment?
- Arteriography
- Surgical revascularization
Atheroembolic renal disease is caused by what?
Most often seen in whom and when?
- Fragments of atheromatous plaques from aorta or renal artery embolize into intrarenal vessels,
- Most commonly in older adults w/ severe atherosclerosis, esp. following surgery on AAA repaire, aortography, or intra-aortic cannulization
What occurs when atheroembolism throws?
to a sudden obstruction of blood flow in the renal artery or their main segmental branches and to ischemia of kidney => infarction w/ renal dysfunction of failure
Hemorrhagic renal infarcts are due to what?
renal vein thrombosis
What is the most common cause of renal infarct?
Embolism from mural thrombus on left side of heart
Renal infarct occurs when what?
- Decreased blood flow (25% of CO)
- End-organ vascular supply
- Lack of collateral circulation
What are OTHER sources of emboli leading to renal infarcts?
- Mural thrombosis from left atrium/ventricle due to MI
- Vegetative endocarditis
- Aortic aneurysms
- Aortic atherosclerosis
Due to the lack of collateral blood supply, how do renal infarcts appear morphologically?
Shape?
- Sharply demarcated, pale, yellow-white areas of coagulative necrosis
- Wedge-shaped
-
Sickle Cell Nephropathy is seen both the disease and can manifest with sickle trait as well.
- What are the sx?
- Hematuria
- Hyposthenuria
- 30% will have sub-nephrotic proteinuria
How does sickle cell nephropathy alter the kidney?
- Patchy papillary necrosis
- Cortex is pale d/t diffuse ischemic
- Vascular disruption
- Diffuse Cortical Necrosis is what?
- Caused by?
- Can lead to?
- Coagulative necrosis of both glomeruli and tubules
- Obstetic MRGENCIES, septic shock, surgery complications
- Systemic hypoperfusion or hypoxia
