L13- Renal Vasculature Diseases Flashcards
list the 3 categories of vascular diseases with renal involvement
- HTN: benign or malignant nephrosclerosis
- renal arterial sclerosis
- thromobotic microangiopathy: HUS (hemolytic uremic syndrome), TTP (thrombotic thrombocytopenic purpura)
Benign hypertensive nephrosclerosis is usually (1) with a (normal/reduced) GFR. Risk factors include the following: (3).
1- asymptomatic
2- normal or slightly reduced GFR
3- black (8-fold), higher BP, 2nd underlying CKD (i.e. DM)
Benign hypertensive nephrosclerosis results from existing HTN causing (1) in arteries and therefore a (2) change in caliber. (2) results in (3) to the arterioles and capillaries and long-term can cause (4) to the following in the kidney, (5).
1- medial / intimal thickening (of large/small vessels) 2- luminal narrowing 3- dec pressure transmission 4- ischemic injury 5- glomerulus, tubules, interstitium
describe the vascular changes in benign hypertensive nephrosclerosis
- medial / intimal thickening; responding to hemodynamic changes (inc BP i guess)
- hyaline atherosclerosis: extravasation off plasma proteins thru injured endothelium (in small arteries of the kidney)
describe the glomerular changes in benign hypertensive nephrosclerosis
- global sclerosis is a ischemic injury –> nephron loss
- FSGS is a adaptive injury due to compensatory hyperfiltration due to nephron loss (compounding factor)
describe the tubular and interstitial changes in benign hypertensive nephrosclerosis
- tubular atrophy
- interstitial fibrosis (ischemic mediated)
describe the clinical presentation of benign hypertensive nephrosclerosis
(asymptomatic most of the time)
-long standing h/o HTN (yrs)
-slowly progressive serum creatinine elevation
-mild proteinuria (<1g/day via segmental scarring)
-no microscopic hematuria
(very few progress to ESRD)
Diagnosis of benign hypertensive nephrosclerosis involves the patient having (1) in their history and (2) urine results. Other related manifestations to this condition are (3).
1- HTN (long-standing)
2- mild proteinuria
3- LVH, retinopathy, stroke
Malignant hypertensive nephrosclerosis is associated with a BP of (1) and develops in patients with (2). It is most common in (3) people (age/race/gender).
1- >180/120 or diastolic >130
2- essential HTN OR secondary HTN (pheochromocytoma, primary hyperaldosteronism)
3- young black males
Malignant hypertensive nephrosclerosis results from severe HTN causing (1) in arteries and therefore a (2) change in caliber. (2) results in (3) to the arterioles and capillaries, instead of (4) seen in the benign form.
1- medial / intimal thickening of large and small arteries
2- luminal narrowing
3- ‘breakthrough’ transmission of high pressure
4- dec pressure transmission
In malignant hypertensive nephrosclerosis, (1) will cause (2) injury in the (3). (2) results in the following, (4), going into extravacular space, which will eventually progress to (5).
1- severe HTN
2- endothelial
3- arterioles, capillaries
4- fibrinogen, platelet deposition, plasma protein
5- fibrinoid necrosis + intravascular thrombosis
Malignant hypertensive crisis usually affects (1) organs, taking (2) time for those organs to be damaged. (3) is required in order to spare irreversible organ damage, although (4) is most likely.
1- kidney, brain, eyes, heart, lungs, large BVs
2- hrs - days
3- IV anti-hypertensives
4- >50% mortality w/in 3 mos
describe the symptoms of malignant hypertensive crisis in: kidney, brain, heart, lungs, large vessels, eyes
- Kidney: marked proteinuria, microscopic/gross hematuria, elevated creatinine (ARF)
- Brain: n/v, HA, encephalopathy, stroke, seizures
- Heart: acute MI
- Lungs: pulmonary edema
- Vessels: aortic dissection
- Eyes: blurry vision, loss of vision
list the thrombotic microangiopathies (TMA)
HUS: hemolytic uremic syndrome
TTP: thrombotic thrombocytopenia purpura
HUS / TTP are characterized by (1) causing (2) throughout the body. (2) will cause injury to (3), which eventually leads to (4). (2) mostly leads to (5) in the (6) organs.
1- abnormal platelet aggregation (=> low platelet count / thrombocytopenia)
2- thrombosis in arterioles and capillaries (small vessels)
3- RBCs
4- microangiopathic hemolytic anemia (fragmented RBCs)
5- ischemic injury
6- kidney, brain, heart
HUS is classically seen in (1) people usually after (2). It mostly effects (3) organ, leaving (4) with less involvement.
Other associated microbes are (5) and possible drugs that cause this are (6).
1- children
2- 1 week after episode of bloody diarrhea due to enterohemorrhagic E. Coli
3- kidney (severe renal failure)
4- less CNS involvement
5- viruses, Shigella, Salmonella
6- quinine (tonic water), gemcitabine, cyclosporine, ticlopidine, oral contraceptives
HUS involves (1) more than (2) and TTP involves (2) more than (1)
1- kidney (HUS)
2- CNS (TTP)
list the clinical and laboratory findings in HUS/TTP
- microangiopathic hemolytic anemia – schistocytes in peripheral blood smear
- thrombocytopenia
- purpuric rash
- ARF: mild-moderate proteinuria, hematuria
- CNS: HA, confusion, seizure, stroke
- fever
TTP mostly effects (1), leaving (2) more spared or with less severe effects. It is often associated with (3).
1- brain/CNS
2- kidney (less severe renal failure)
3- SLE, HIV, hematological malignancy
Renal Artery Stenosis (RAS) involves a occlusion of (one/both) renal arteries, usually due to (2) and sometimes due to (3). Other minor causes include (4).
1- one or both
2- atheromatous plaque (75-90%)
3- fibromuscular dysplasia (10-25%)
4- Takayasu’s arteries, aortic/renal artery dissection
The main consequence of RAS is (1) causing (2) to glomeruli, (3) to tubules, and (4) to interstitium.
Alternatively, (5) can result from RAS because of (6).
1- ischemic nephropathy (=> diffuse ischemic atrophy)
2- crowding glomeruli (due to scarring)
3- tubular atrophy
4- fibrotic interstitium
5- no arteriolosclerosis of affected kidney
6- arterioles are protected from high pressure transmission from stenotic artery –> hypertensive arteriosclerosis of unaffected contra-lateral kidney (due to inc systemic HTN)
what are the main risk factors for RAS (who does it affect the most)
- HTN or malignant HTN
- CAD
- renal insufficiency
RAS usually presents with (1) and (2). Most patients have (3), with onset <30 or >55 y/o which suddenly progresses to (4) and results in intermittent (5).
1- flank or epigastric bruit (abnormal sound)
2- ARF
3- HTN
4- accelerated / malignant and uncontrolled HTN (in someone previously well-controlled)
5- flash pulmonary edema: acute pulmonary venous congestion / volume overload
list the diagnostic imaging studies used for RAS (indicate the gold standard)
- Renal US: asymmetrical kidney size (smaller on side with RAS)
- Renal Artery Doppler: measure blood flow velocities in renal arteries compared to aorta; ratio >3.5 is significant
- MRA renal arteries: anatomical
- CT angiogram: anatomical
- **Renal arteriogram = GOLD standard
RAS requires an angioplasty and stent if there is….
- uncontrolled HTN
- declining renal function (elevated Cr)
- recurrent pulmonary edema
Adult PKD is a (AD/AR) disease
Childhood PKD is a (AD/AR) disease
(polycystic kidney disease)
Adult- autosomal dominant [polycystin 1,2]
Childhood- autosomal recessive [fibrocystin]
______ are systemic diseases associated with cystic kidney disease
- Von Hippel-Lindau Syndrome (VHLS)
- tuburous sclerosis (TS)
acquired cystic kidney disease is termed as either (1) or (2)
1- benign simple cysts
2- medullary sponge kidney
Adult PKD (ADPKD) is characterized by (1) and usually will present clinically with (2)
1- development of multiple fluid filled cysts –> inc kidney size
2- usually silent, <50% of cases are diagnosed during patient’s lifetime
(usually if found, treating HTN is only management)
ADPKD mostly results from (1) mutation, but (2) is also a common mutation
1- abnormal Chr. 16p13.3 PKD1 gene (85-90%)
2- abnormal Chr. 4q21 PKD2 gene: milder phenotype, later onset of smaller and fewer cysts with slower progression and later age of ESRD (10-15%)
The proposed mechanism of PKD is that mutations in certain nephron proteins (polycystin 1/2 in adults, fibrocystin in children, or nephrocystin) lead to altered (1) and (2), resulting (3). (3) causes the following 3 processes, (4), which will lead to cyst formation.
1- Ca flux
2- mechanosensation by tubular cilia
3- altered tubular epithelial growth and differentiation
4- abnormal ECM, cell proliferation, fluid secretion
cyst growth in ADPKD will lead to (1) and (2) as final consequences, but they are limited by (3) and (4)
1- compression and destruction of normal adjacent parenchyma
2- over-perfused glomeruli
3- <5% nephrons involved
4- no evidence of FSGS
list the 4 renal manifestations resulting from PKD (include reasons why and % chance they are evident)
1) HTN (50-70%): cysts compress renal vessels => RAAS activation
2) hematuria (50-60%): ruptured cyst in collecting system
3) flank pain (60%): stretching of renal capsule
4) nephrolithiasis (30%): >50% uric stones, Ca-oxalate
list the extra-renal manifestations of PKD
- hepatic cysts, pancreatic cysts
- cerebral aneurysms
- cardiac valve disease (MVP, AR)
- colonic diverticular disease
- abdominal wall + inguinal hernia
The extra-renal manifestations of ADPKD usually occur with increase in (1) and present as (2). (3) usually remains intact, but can cause pain due to (4).
1- age (80% over 30)
2- asymptomatic or mild
3- synthetic liver function intact
4- pain from distension on liver capsule
Childhood PKD is the result of a (1) mutation on the (2) gene. Cysts become evident at (3) and they arise from (4) part of the kidney. (5) is usually associated and (6) is the typical outcome.
1- autosomal recessive
2- PKHD1 on Chr.6p21-23, protein fibrocystin
3- birth, kidneys are enlarged too
4- collecting tubules
5- hepatic fibrosis
6- variable, but death in infancy or childhood
A simple renal cyst occurs as (one/multiple) events, more common in (2) people of age. (T/F) they have a predisposition for CRF and or cancer.
1- either one or multiple
2- older people
3- F
(only clinical finding would be pain due to cystic rupture)
Alport’s syndrome is the result of a defect in (1) due to a (2) inherited mutation in (3) gene. It mostly affects (4) people (age/gender).
1- collagen IV synthesis (basement membrane)
2- X-linked (80%), AR/AD (20%)
3- COL4A4, COL4A5
4- males > females, age 5-20 y/o
Alport’s syndrome is evident by the following symptoms:
- Nephritis: hematuria**, proteinuria, renal failure
- Nerve deafness (55%)
- eye disorders (15-30%, juvenile form)
- (rare) hematological disorders: thrombocytopenia
describe the microscopic appearance of the kidney in Alport’s syndrome
LM: variation in GBM thickness, FSGS
IF: negative + negative segmental stain for α-3,4,5 collagen GB
EM: thin GBM (<150nm), splitting and lamination of GBM
