Lecture 6: Renovascular Hypertension

Question 1

How much of cardiac outflow goes to the kidner?

Answer 1

20% , 1L/min
Kidney requires plasma to filter waste products
Important component of TPR

Question 2

What can renovascular hypertension be caused by?

Answer 2

Restriction of blood flow by:

• cysts, in kidney, blocks arteries within kidney itself, genetic
• atheroma, in arteries running toward kidneys

Question 3

What is autosomal dominant polycystic kidney disease (ADPKD)?

Answer 3

One of the most common genetic diseases
1 in 700 people
Autosomal dominant inheritance
No family history in 10% - spontaneous mutation, adoption, false paternity

Question 4

Where can cysts occur in autosomal dominant polycystic kidney disease (ADPKD)?

Answer 4

Ductal organs:
Kidneys (100%)
Gut, pancreas spleen (80%)
Liver (70%)
Heart (15%)
Blood vessels (10%)

Question 5

What are the two stages of ADPKD?

Answer 5

Early hypertension

Renal Failure - cysts crush normal tissue surrounding them

Question 6

What does growth of ADPKD cysts depend on?

Answer 6

Obstruction to nephron or net fluid secretion by cyst cells
Abnormal cell proliferation
Abnormally compliant basement membrane - signals: cross talk with layer on top tell cells how to behaves, lose the signal = cyst formation

Question 7

Where do ADPKD renal cysts form?

Answer 7

Appear in utero
From only 1% of nephrons
Thin walled dilations from any part
Lose continuity with nephron as they grow
Can reach several cm in diameter

Question 8

How many nephrons in a kidney?

Answer 8

100,000

Question 9

What are the two types of ADPKD mutations?

Answer 9

PKD1 (chromosome 16)

• encodes polycystin-1
• 85% of cases
• > 64 different mutations
• allelic heterogenity

PKD2 (chromosome 4)

• encodes polycystin-2
• 15% of cases
• > 50 different mutations

Look identical clinically but have different genetic origins

Question 10

What is the role of the polycystin complex?

Answer 10

Basement membrane integrity (polycystin 1)
Ion channels (polycystin 2)

Question 11

How does APDKD affect BP?

Answer 11

Slightly increases SBP and DBP

Question 12

How does APDKD affect renal function?

Answer 12

Significantly lowers renal blood flow

Renal vascular resistance increases due to presence of early cysts

Question 13

How does APDKD affect vessels?

Answer 13

Intrarenal arteries are stretched and compressed by enlarging cysts
Glomerular arteriole baroreceptors detect BP changes
Pre glomerular cells granular cells release renin in response to low BP

Question 14

How does APDKD affect hormones?

Answer 14

Risk of reabsorbing more Na+ than usual and expanding ECF volume/blood volume
Significantly increases plasma renin activity and aldosterone levels

Question 15

Increase in BP causes a ____ in renin

Answer 15

Decrease

Question 16

Decrease in BP causes an ____ increase in renin

Answer 16

Increase

Question 17

Where is renin found in ADPKD?

Answer 17

Enlarged juxtaglomerular cells
Vessels
Cells lining the cyst walls
Chronic expression of renin leads to it going to abnormal places

Question 18

How does APDKD affect fluid volume?

Answer 18

Significantly increases exchangeable Na

Question 19

What physiological process occur as a result of ADPKD?

Answer 19

Reduced renal blood flow
Increased plasma renin (released by granular cells)
Elevated plasma aldosterone
High body Na and plasma volume
High BP

Question 20

What is renal artery stenosis (RAS)?

Answer 20

Significant (>70%) obstruction to renal blood flow by:

• atheroma (70%)
• fibromuscular dysplasia (FMD) (25%)

Question 21

What is atheromatous RAS?

Answer 21

Irregular choking
Associated with atheroma generally in the:
- heart
- brain 
- legs 
Tends to be in:
- men
- older people

Question 22

What is fibromuscular dysplasia (FMD) RAS?

Answer 22

Distortion of architecture of arteries
Abnormal growth in the renal artery wall, coils/twists = obstruction
Affects young women

Question 23

Why do ACE inhibitor drugs cause renal failure in patients with RAS to both kidneys?

Answer 23

Angiotensin maintains a high GFR when threatened with low BP
GFR is determined by pressure in glomerular capillaries
Pressure is result of blood therefore keep as much blood in as possible
Constriction of post glomerular arterioles = banks blood up in glomerulus = pressure is higher in glomerulus
ACE inhibitor decreases angiotensin levels = lets blood escape = fall in GFR