Lecture 13 - Role of the Kidney in the Regulation of BP Flashcards
MAP equation?
MAP = CO x SVR
SVR = systemic vascular resistance = TPR = total peripheral resistance
CO equation?
CO = HR x SV
3 factors affecting CO?
- Autonomic NS: contractility and rate
- Preload
- Afterload
What makes up systemic vascular resistance?
- Neurohumoral constrictor/vasodilator systems
2. Locally acting constrictor/vasodilator systems
What is the mean circulatory filling pressure? What 2 factors determine it?
Integrative measure of the fullness of the system (arterial, mostly venous, and capillary)
- BV
- Cardiovascular capacitance due to varying vasoconstrictor/dilator tone
How is mean circulatory mean pressure measured? Normal value?
Stop CO and measure BP when arterial and venous pressures equalize
= 7 mmHg
Effect on plasma [Na+] when ingested Na+ increases?
NO EFFECT, water follows (thirst and ADH) to keep it constant at ALL TIMES => ECF expansion => increase in body weight
What does overperfusion of an organ/whole body lead to?
Increased resistance of flow to the organ via autoregulation
What does autoregulation involve?
- Myogenic regulation of smooth muscle cells
2. Local autocrine and paracrine signaling
2 factors affecting the effective blood volume?
- Capacitance
2. Mean circulatory filling pressure
3 immediate effects of increasing BV if ANS is blocked?
- CO increases
- Arterial BP rises
- Urinary output increases
How to accurately measure daily Na+ intake?
Measure Na+ in urine, since all of it will be excreted in the steady state
What does the pressure associated with a particular Na+ intake correspond to?
Pressure needed to excrete load of Na+
How does the kidney sense pressure in the aorta aka the renal perfusion pressure?
Changes sensed in renal medulla
How is the signal of changing renal perfusion pressure transduced into changes in renal salt/volume excretion?
Renal perfusion is transduced to high renal medullary interstitial hydrostatic pressure, which increases natriuresis and urine output:
Systemic arterial pressure is transmitted through the renal artery => changes in BP are sensed/transduced as changes in medullary blood flow because the myogenic autoregulation is not as strong in the medulla =>
- High medullary flow increases interstitial pressure (when the capsule is intact) => increasing natriuresis
- Low medullary flow => decreases interstitial pressure => decreasing natriuresis
What part of the kidney’s flow varies linearly with arterial pressure over a wide range?
Medullary blood flow
What part of the kidney’s flow varies linearly with arterial pressure over a wide range?
Medullary blood flow
Would a vasoconstrictor administered to the medulla affect cortical blood flow?
NOPE
What is necessary for high renal perfusion to be transduced to high medullary interstitial hydrostatic pressure?
Only happens when the renal capsule is intact
Describe the renal function curve and how it can be altered.
Arterial pressure vs Na+ intake or output =>
- Shift to the right/left:
- Right: at every level of Na+ intake, your BP is higher than normal => low medullary blood flow
- Left: at every level of Na+ intake, your BP is lower than normal => high medullary blood flow - Lower slope of the curve: BP is more “salt-sensitive” meaning small changes in Na+ will cause larger changes in BP
- Normal curve, but elevated BP set-point because that patient maintains continuous increase in Na+ intake so BP is continuously raised
Can a very small change in Na+ reabsorption lead to chronic HT? Example? What do we call?
YUP
e.g. aldosterone secreting tumor, which only acts on CD where only 3-5% of Na+ is reabsorbed => secondary cause of HT
Can we demonstrate pressure natriuresis in young healthy patients?
NOPE because kidneys regulate BP too well so you would never need to use this system to get rid of excess volume
Timing of maximal effect of Ang II?
<20 min
How does Ang II impact pressure natriuresis?
It impairs it
Effect of high Ang II on renal function curve?
Flatter curve
Effect of Ang II blockade on renal function curve?
Shift to the left and flatter curve
Example of Ang II blocker?
ACE inhibitor
What does a healthy renal function curve look like?
Almost one straight line as the RAA system makes sure Na+ intake does not impact BP => hybrid of high Ang II and Ang II blockade curves
Describe the Goldblatt Hypertension experiments. Significance?
GOLDBLATT II: ONE CLIPPED KIDNEY/ONE NORMAL ONE:
- Renal artery has a constriction clip that can decrease renal perfusion pressure to increase renin secretion
- Ang II increases systemic BP and salt/Na+ retention and almost restores perfusion pressure to the clipped kidney
- Other kidney senses increase in arterial BP => pressure natriuresis
GOLDBLATT I: ONLY ONE KIDNEY AND ONE CLIP:
- Renal arteries have a constriction clip that can decrease renal perfusion pressure to increase renin secretion
- Ang II increases systemic BP and salt/Na+ retention and almost restores perfusion pressure to the kidney
- No pressure natriuresis
=> both of these forms of HT can occur clinically due to narrowing of one or both renal arteries
What is the Goldblatt I experiment equivalent to?
2 kidneys with 2 clips => suprarenal coarctation of the aorta (narrowing of the aorta) => high BP in arms and low in legs
What may limit pressure natriuresis?
Humoral effects of Ang II and HT damage in a chronic state
What does volume status look like in a patient with ESSENTIAL HT? What does this imply? What to note?
Always relative volume overload in chronic state (increase in mean circulatory filling pressure), implying a central role for the kidney => subtle primary renal defect in salt excretion (right shifted renal function curve)
Why do a lot of HT patients require combination therapy (aka more than 1 drug)?
- Diuretics are limited by compensatory RAA system and SNS
2. Vasodilators are limited by RAA system and SNS
% of US adults with HT?
30% (70% of those over 65)
What could the Goldblatt clip represent?
- Atherosclerotic plaque
2. Fibromuscular dysplasia of renal artery wall
Are the Goldblatt 1 and 2 experiments showing renin or volume dependent HT?
- Goldblatt II: relatively lower volume because of pressure natriuresis (may increase in chronic phase due to RAAS) => renin-dependent HT
- Goldblatt I: relatively higher volume because NO pressure natriuresis => volume-dependent HT (also renin obviously)
So is increased medullary blood flow due to medullary vasodilation?
No, the increased flow causes the vasodilation and vice versa
Is there myogenic regulation in medullary vessels?
NOPE
