Lecture 13 - Role of the Kidney in the Regulation of BP

Question 1

MAP equation?

Answer 1

MAP = CO x SVR

SVR = systemic vascular resistance = TPR = total peripheral resistance

Question 2

CO equation?

Answer 2

CO = HR x SV

Question 3

3 factors affecting CO?

Answer 3

1. Autonomic NS: contractility and rate
2. Preload
3. Afterload

Question 4

What makes up systemic vascular resistance?

Answer 4

1. Neurohumoral constrictor/vasodilator systems

2. Locally acting constrictor/vasodilator systems

Question 5

What is the mean circulatory filling pressure? What 2 factors determine it?

Answer 5

Integrative measure of the fullness of the system (arterial, mostly venous, and capillary)

1. BV
2. Cardiovascular capacitance due to varying vasoconstrictor/dilator tone

Question 6

How is mean circulatory mean pressure measured? Normal value?

Answer 6

Stop CO and measure BP when arterial and venous pressures equalize

= 7 mmHg

Question 7

Effect on plasma [Na+] when ingested Na+ increases?

Answer 7

NO EFFECT, water follows (thirst and ADH) to keep it constant at ALL TIMES => ECF expansion => increase in body weight

Question 8

What does overperfusion of an organ/whole body lead to?

Answer 8

Increased resistance of flow to the organ via autoregulation

Question 9

What does autoregulation involve?

Answer 9

1. Myogenic regulation of smooth muscle cells

2. Local autocrine and paracrine signaling

Question 10

2 factors affecting the effective blood volume?

Answer 10

1. Capacitance

2. Mean circulatory filling pressure

Question 11

3 immediate effects of increasing BV if ANS is blocked?

Answer 11

1. CO increases
2. Arterial BP rises
3. Urinary output increases

Question 12

How to accurately measure daily Na+ intake?

Answer 12

Measure Na+ in urine, since all of it will be excreted in the steady state

Question 13

What does the pressure associated with a particular Na+ intake correspond to?

Answer 13

Pressure needed to excrete load of Na+

Question 14

How does the kidney sense pressure in the aorta aka the renal perfusion pressure?

Answer 14

Changes sensed in renal medulla

Question 15

How is the signal of changing renal perfusion pressure transduced into changes in renal salt/volume excretion?

Answer 15

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 =>

1. High medullary flow increases interstitial pressure (when the capsule is intact) => increasing natriuresis
2. Low medullary flow => decreases interstitial pressure => decreasing natriuresis

Question 16

What part of the kidney’s flow varies linearly with arterial pressure over a wide range?

Answer 16

Medullary blood flow

Question 17

What part of the kidney’s flow varies linearly with arterial pressure over a wide range?

Answer 17

Medullary blood flow

Question 18

Would a vasoconstrictor administered to the medulla affect cortical blood flow?

Answer 18

NOPE

Question 19

What is necessary for high renal perfusion to be transduced to high medullary interstitial hydrostatic pressure?

Answer 19

Only happens when the renal capsule is intact

Question 20

Describe the renal function curve and how it can be altered.

Answer 20

Arterial pressure vs Na+ intake or output =>

1. 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
2. Lower slope of the curve: BP is more “salt-sensitive” meaning small changes in Na+ will cause larger changes in BP
3. Normal curve, but elevated BP set-point because that patient maintains continuous increase in Na+ intake so BP is continuously raised

Question 21

Can a very small change in Na+ reabsorption lead to chronic HT? Example? What do we call?

Answer 21

YUP

e.g. aldosterone secreting tumor, which only acts on CD where only 3-5% of Na+ is reabsorbed => secondary cause of HT

Question 22

Can we demonstrate pressure natriuresis in young healthy patients?

Answer 22

NOPE because kidneys regulate BP too well so you would never need to use this system to get rid of excess volume

Question 23

Timing of maximal effect of Ang II?

Answer 23

<20 min

Question 24

How does Ang II impact pressure natriuresis?

Answer 24

It impairs it

Question 25

Effect of high Ang II on renal function curve?

Answer 25

Flatter curve

Question 26

Effect of Ang II blockade on renal function curve?

Answer 26

Shift to the left and flatter curve

Question 27

Example of Ang II blocker?

Answer 27

ACE inhibitor

Question 28

What does a healthy renal function curve look like?

Answer 28

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

Question 29

Describe the Goldblatt Hypertension experiments. Significance?

Answer 29

GOLDBLATT II: ONE CLIPPED KIDNEY/ONE NORMAL ONE:

1. Renal artery has a constriction clip that can decrease renal perfusion pressure to increase renin secretion
2. Ang II increases systemic BP and salt/Na+ retention and almost restores perfusion pressure to the clipped kidney
3. Other kidney senses increase in arterial BP => pressure natriuresis

GOLDBLATT I: ONLY ONE KIDNEY AND ONE CLIP:

1. Renal arteries have a constriction clip that can decrease renal perfusion pressure to increase renin secretion
2. Ang II increases systemic BP and salt/Na+ retention and almost restores perfusion pressure to the kidney
3. No pressure natriuresis

=> both of these forms of HT can occur clinically due to narrowing of one or both renal arteries

Question 30

What is the Goldblatt I experiment equivalent to?

Answer 30

2 kidneys with 2 clips => suprarenal coarctation of the aorta (narrowing of the aorta) => high BP in arms and low in legs

Question 31

What may limit pressure natriuresis?

Answer 31

Humoral effects of Ang II and HT damage in a chronic state

Question 32

What does volume status look like in a patient with ESSENTIAL HT? What does this imply? What to note?

Answer 32

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)

Question 33

Why do a lot of HT patients require combination therapy (aka more than 1 drug)?

Answer 33

1. Diuretics are limited by compensatory RAA system and SNS

2. Vasodilators are limited by RAA system and SNS

Question 34

% of US adults with HT?

Answer 34

30% (70% of those over 65)

Question 35

What could the Goldblatt clip represent?

Answer 35

1. Atherosclerotic plaque

2. Fibromuscular dysplasia of renal artery wall

Question 36

Are the Goldblatt 1 and 2 experiments showing renin or volume dependent HT?

Answer 36

• 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)

Question 37

So is increased medullary blood flow due to medullary vasodilation?

Answer 37

No, the increased flow causes the vasodilation and vice versa

Question 38

Is there myogenic regulation in medullary vessels?

Answer 38

NOPE