Lecture 6: Renovascular Hypertension Flashcards
How much of cardiac outflow goes to the kidner?
20% , 1L/min
Kidney requires plasma to filter waste products
Important component of TPR
What can renovascular hypertension be caused by?
Restriction of blood flow by:
- cysts, in kidney, blocks arteries within kidney itself, genetic
- atheroma, in arteries running toward kidneys
What is autosomal dominant polycystic kidney disease (ADPKD)?
One of the most common genetic diseases
1 in 700 people
Autosomal dominant inheritance
No family history in 10% - spontaneous mutation, adoption, false paternity
Where can cysts occur in autosomal dominant polycystic kidney disease (ADPKD)?
Ductal organs: Kidneys (100%) Gut, pancreas spleen (80%) Liver (70%) Heart (15%) Blood vessels (10%)
What are the two stages of ADPKD?
Early hypertension
Renal Failure - cysts crush normal tissue surrounding them
What does growth of ADPKD cysts depend on?
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
Where do ADPKD renal cysts form?
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
How many nephrons in a kidney?
100,000
What are the two types of ADPKD mutations?
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
What is the role of the polycystin complex?
Basement membrane integrity (polycystin 1) Ion channels (polycystin 2)
How does APDKD affect BP?
Slightly increases SBP and DBP
How does APDKD affect renal function?
Significantly lowers renal blood flow
Renal vascular resistance increases due to presence of early cysts
How does APDKD affect vessels?
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
How does APDKD affect hormones?
Risk of reabsorbing more Na+ than usual and expanding ECF volume/blood volume
Significantly increases plasma renin activity and aldosterone levels
Increase in BP causes a ____ in renin
Decrease
Decrease in BP causes an ____ increase in renin
Increase
Where is renin found in ADPKD?
Enlarged juxtaglomerular cells
Vessels
Cells lining the cyst walls
Chronic expression of renin leads to it going to abnormal places
How does APDKD affect fluid volume?
Significantly increases exchangeable Na
What physiological process occur as a result of ADPKD?
Reduced renal blood flow Increased plasma renin (released by granular cells) Elevated plasma aldosterone High body Na and plasma volume High BP
What is renal artery stenosis (RAS)?
Significant (>70%) obstruction to renal blood flow by:
- atheroma (70%)
- fibromuscular dysplasia (FMD) (25%)
What is atheromatous RAS?
Irregular choking Associated with atheroma generally in the: - heart - brain - legs Tends to be in: - men - older people
What is fibromuscular dysplasia (FMD) RAS?
Distortion of architecture of arteries
Abnormal growth in the renal artery wall, coils/twists = obstruction
Affects young women
Why do ACE inhibitor drugs cause renal failure in patients with RAS to both kidneys?
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
