L13- Renal Vasculature Diseases

Question 1

list the 3 categories of vascular diseases with renal involvement

Answer 1

• HTN: benign or malignant nephrosclerosis
• renal arterial sclerosis
• thromobotic microangiopathy: HUS (hemolytic uremic syndrome), TTP (thrombotic thrombocytopenic purpura)

Question 2

Benign hypertensive nephrosclerosis is usually (1) with a (normal/reduced) GFR. Risk factors include the following: (3).

Answer 2

1- asymptomatic
2- normal or slightly reduced GFR
3- black (8-fold), higher BP, 2nd underlying CKD (i.e. DM)

Question 3

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).

Answer 3

1- medial / intimal thickening (of large/small vessels)
2- luminal narrowing
3- dec pressure transmission
4- ischemic injury
5- glomerulus, tubules, interstitium

Question 4

describe the vascular changes in benign hypertensive nephrosclerosis

Answer 4

• 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)

Question 5

describe the glomerular changes in benign hypertensive nephrosclerosis

Answer 5

• global sclerosis is a ischemic injury –> nephron loss

- FSGS is a adaptive injury due to compensatory hyperfiltration due to nephron loss (compounding factor)

Question 6

describe the tubular and interstitial changes in benign hypertensive nephrosclerosis

Answer 6

• tubular atrophy

- interstitial fibrosis (ischemic mediated)

Question 7

describe the clinical presentation of benign hypertensive nephrosclerosis

Answer 7

(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)

Question 8

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).

Answer 8

1- HTN (long-standing)
2- mild proteinuria
3- LVH, retinopathy, stroke

Question 9

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).

Answer 9

1- >180/120 or diastolic >130
2- essential HTN OR secondary HTN (pheochromocytoma, primary hyperaldosteronism)
3- young black males

Question 10

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.

Answer 10

1- medial / intimal thickening of large and small arteries
2- luminal narrowing
3- ‘breakthrough’ transmission of high pressure
4- dec pressure transmission

Question 11

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).

Answer 11

1- severe HTN
2- endothelial
3- arterioles, capillaries
4- fibrinogen, platelet deposition, plasma protein
5- fibrinoid necrosis + intravascular thrombosis

Question 12

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.

Answer 12

1- kidney, brain, eyes, heart, lungs, large BVs
2- hrs - days
3- IV anti-hypertensives
4- >50% mortality w/in 3 mos

Question 13

describe the symptoms of malignant hypertensive crisis in: kidney, brain, heart, lungs, large vessels, eyes

Answer 13

• 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

Question 14

list the thrombotic microangiopathies (TMA)

Answer 14

HUS: hemolytic uremic syndrome

TTP: thrombotic thrombocytopenia purpura

Question 15

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.

Answer 15

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

Question 16

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).

Answer 16

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

Question 17

HUS involves (1) more than (2) and TTP involves (2) more than (1)

Answer 17

1- kidney (HUS)

2- CNS (TTP)

Question 18

list the clinical and laboratory findings in HUS/TTP

Answer 18

• microangiopathic hemolytic anemia – schistocytes in peripheral blood smear
• thrombocytopenia
• purpuric rash
• ARF: mild-moderate proteinuria, hematuria
• CNS: HA, confusion, seizure, stroke
• fever

Question 19

TTP mostly effects (1), leaving (2) more spared or with less severe effects. It is often associated with (3).

Answer 19

1- brain/CNS
2- kidney (less severe renal failure)
3- SLE, HIV, hematological malignancy

Question 20

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).

Answer 20

1- one or both
2- atheromatous plaque (75-90%)
3- fibromuscular dysplasia (10-25%)
4- Takayasu’s arteries, aortic/renal artery dissection

Question 21

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).

Answer 21

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)

Question 22

what are the main risk factors for RAS (who does it affect the most)

Answer 22

• HTN or malignant HTN
• CAD
• renal insufficiency

Question 23

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).

Answer 23

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

Question 24

list the diagnostic imaging studies used for RAS (indicate the gold standard)

Answer 24

• 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

Question 25

RAS requires an angioplasty and stent if there is....

Answer 25

- uncontrolled HTN - declining renal function (elevated Cr) - recurrent pulmonary edema

Question 26

Adult PKD is a (AD/AR) disease Childhood PKD is a (AD/AR) disease

Answer 26

(polycystic kidney disease) Adult- autosomal dominant [polycystin 1,2] Childhood- autosomal recessive [fibrocystin]

Question 27

______ are systemic diseases associated with cystic kidney disease

Answer 27

- Von Hippel-Lindau Syndrome (VHLS) | - tuburous sclerosis (TS)

Question 28

acquired cystic kidney disease is termed as either (1) or (2)

Answer 28

1- benign simple cysts | 2- medullary sponge kidney

Question 29

Adult PKD (ADPKD) is characterized by (1) and usually will present clinically with (2)

Answer 29

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)

Question 30

ADPKD mostly results from (1) mutation, but (2) is also a common mutation

Answer 30

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%)

Question 31

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.

Answer 31

1- Ca flux 2- mechanosensation by tubular cilia 3- altered tubular epithelial growth and differentiation 4- abnormal ECM, cell proliferation, fluid secretion

Question 32

cyst growth in ADPKD will lead to (1) and (2) as final consequences, but they are limited by (3) and (4)

Answer 32

1- compression and destruction of normal adjacent parenchyma 2- over-perfused glomeruli 3- <5% nephrons involved 4- no evidence of FSGS

Question 33

list the 4 renal manifestations resulting from PKD (include reasons why and % chance they are evident)

Answer 33

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

Question 34

list the extra-renal manifestations of PKD

Answer 34

- hepatic cysts, pancreatic cysts - cerebral aneurysms - cardiac valve disease (MVP, AR) - colonic diverticular disease - abdominal wall + inguinal hernia

Question 35

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).

Answer 35

1- age (80% over 30) 2- asymptomatic or mild 3- synthetic liver function intact 4- pain from distension on liver capsule

Question 36

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.

Answer 36

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

Question 37

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.

Answer 37

1- either one or multiple 2- older people 3- F (only clinical finding would be pain due to cystic rupture)

Question 38

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).

Answer 38

1- collagen IV synthesis (basement membrane) 2- X-linked (80%), AR/AD (20%) 3- COL4A4, COL4A5 4- males > females, age 5-20 y/o

Question 39

Alport's syndrome is evident by the following symptoms:

Answer 39

- Nephritis: hematuria**, proteinuria, renal failure - Nerve deafness (55%) - eye disorders (15-30%, juvenile form) - (rare) hematological disorders: thrombocytopenia

Question 40

describe the microscopic appearance of the kidney in Alport's syndrome

Answer 40

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