Exam #4: Renal Hormones & Autacoids

Question 1

Describe the two intrinsic renal mechanism for autoregulation of renal blood flow (RBF) & glomerular filtration rate?

Answer 1

1) Myogenic mechanism= blood vessels resist stretching by contracting in response to increased wall tension i.e. pressure; there is also a reflexive vasodilation in response to decreased wall tension/ stretch
- In the nephron, increased pressure in afferent arteriole= contraction, and prevention of increased hydrostatic pressure in the glomerulus

2) Tubuloglomerular feedback mechanism

Question 2

Describe tubuloglomerular feedback for control of GFR and NaCl delivery to the distal tubule.

Answer 2

1) Increased renal a. pressure= increased GFR & RBF
2) Increased tubular fluid flow
3) Increased flow= less NaCl reabsorption in proximal tubule, b/c less time for reabsorption
4) Eventually, macula densa senses increased flow & NaCl concentration
4) Macula densa secretes ADENOSINE that causes VASOCONSTRICTION of the afferent arteriole

*Note that this effect of adenosine in the kidney is opposite of its normal effect

Question 3

What is the role of the macula densa?

Answer 3

1) Sense increased flow & NaCl concentration
2) Secretion of ADENOSINE that causes VASOCONSTRICTION of the afferent arteriole
3) Inhibition of Renin release–>decrease systemic blood pressure

Question 4

How can tubuloglomerular feedback help prevent excessive fluid losses if there is damage to kidney proximal tubules?

Answer 4

Similar mechanism to increased GFR & RBF, there is LESS water and NaCl sensed at the macula densa–>vasoconstriction of the afferent arteriole to prevent excessive fluid loss from damaged nephrons

Question 5

Give proposed reason why autoregulation is useful.

Answer 5

1) Many activities alter BP, want to uncouple BP from GFR & RBF to keep them CONSTANT
2) Prevent changes in urine output and electrolyte balance based on acute blood pressure changes

Question 6

Can autoregulation still protect the kidney in patients with severe systemic hypertension?

Answer 6

No, these mechanisms stop working at the extremes of blood pressure, but very low and very high

Question 7

Give the names of the autacoids/hormones which can vasodilate the afferent and efferent arterioles.

Answer 7

Vasodilator prostaglandins, PGE2 & PGI2 (prostacyclin)

Question 8

Which hormones/autacoids cause vasoconstriction?

Answer 8

Angiotensin II
NE
Vasopressin (ADH)
Endothelin

Question 9

Explain why drugs that inhibit prostaglandin synthesis can cause renal damage.

Answer 9

Reduced amounts of PGE2 & PGI2 leave vasoconstriction unopposed and can lead to renal damage

Question 10

What common drugs that inhibit prostaglandin synthesis?

Answer 10

NSAIDs e.g. ASA, ibuprofen, naproxen

*****Note that patient’s with chronic renal disease should NOT take NSAIDs–compensatory increase in single nephron GFR is maintained by prostaglandins; knock these out–> immediate renal failure

Question 11

Outline the renin-angiotensin-aldosterone system. Where is each produced?

Answer 11

p. 163

Renin= juxtaglomerular cells of the kidney 
Angiotensinogen= liver 
ACE= lungs and kidneys 
Angiotensinogen II= lung and kidneys 
Aldosterone= adrenal cortex

Question 12

State which cells produce most renin and how renin release is controlled.

Answer 12

Renin is produced by juxtaglomerular cells of the kidney and is secreted in response to decrease arterial pressure, and B1 stimulation

Question 13

Which division of the autonomic nervous system innervates the cells that produce renin?

Answer 13

Stimulation of B1 adrenergic receptors

Question 14

Outline the pathway from angiotensinogen to angiotensin II.

Answer 14

Angiotensin I is converted into Angiotensin II via Angiotensin Converting Enzyme (ACE)

Question 15

Where do renin and angiotensin converting enzyme (ACE) act in this pathway (angiotensinogen to angiotensin II)?

Answer 15

Lung & kidney

Question 16

Describe the effect of angiotensin II on the vascular smooth muscles.

Answer 16

Angiotensin II causes vasoconstriction of vascular smooth muscle

Question 17

Describe the effect of angiotensin II on the adrenal cortex.

Answer 17

Angiotensin II increases secretion of aldosterone from the adrenal cortex

Question 18

Describe the effect of angiotensin II on the efferent arteriole.

Answer 18

In the kidney, angiotensin II preferentially vasoconstricts the efferent arteriole b/c of the vasodilator prostaglandins and NO that act on the afferent arteriole

Question 19

Describe the effect of angiotensin II on the proximal tubule Na+ reabsorption.

Answer 19

Increases the activity of the Na+-H+ exchanger to increase Na+ retention (and consequently, water retention)

Question 20

Describe the effect of angiotensin II on the thirst center.

Answer 20

Increases thirst

Question 21

Describe the effect of angiotensin II on the release of ADH .

Answer 21

Increases secretion of ADH

Question 22

Describe the effect of angiotensin II on sympathetic tone.

Answer 22

Increases sympathetic tone

Question 23

State the two main sources of erythropoietin production. Which organ makes the most (~90%) erythropoietin?

Answer 23

1) Kidney= majority of EPO synthesis

2) Liver

Question 24

What is the effect of erythropoietin on RBC production?

Answer 24

EPO increases RBC production

Question 25

What are the major stimuli for erythropoietin secretion?

Answer 25

Kidney senses oxygen levels and secrets EPO when oxygen levels drop

Question 26

Describe the role of the kidney in making the active form of vitamin D.

Answer 26

Generally, the kidney is responsible for the last step of Vitamin D synthesis

• Vitamin D3 is converted to 25-hydroxycholecaliferol in the liver
• In the kidney, it is converted to 1,25-dihydroxy vitamin D, or Calcitrol

Question 27

What is the major action of the active form of vitamin D? (What is its effect on the intestine? On the kidney? Which effect is more important?)

Answer 27

Intestine= increase absorption of Ca++ & phosphate*

Kidney= increased reabsorption of Ca++ & phosphate

*****Note that the action of Vitamin D in the intestine is more important that the same effect in the kidney

Question 28

Describe the effect of parathyroid hormone on the kidney.

Answer 28

• Formation of the active form of Vitamin D (Calctriol) is stimulated by PTH action on the kidney
• INCREASES Ca++ reabsorption in the kidney but DECREASES reabsorption of phosphate (vs. Calcitriol that increases absorption of both)

Question 29

Describe how chronic renal failure affects the patient’s bones.

Answer 29

• Chronic renal failure= low GFR & increased plasma phosphate
• Elevated phosphate increases PTH
• PTH causes bone resorption

–> “Renal Osteodystrophy”

Question 30

Describe the effects of constricting either the afferent or the efferent arteriole on renal blood flow (RBF).

Answer 30

Afferent= decrease RBF 
Efferent= decrease RBF

Question 31

Describe the effects of constricting either the afferent or the efferent arteriole on GFR.

Answer 31

Afferent= decreased GFR 
Efferent= increased GFR

Question 32

How could you increase the glomerular hydrostatic pressure by constricting the efferent or afferent arterioles?

Answer 32

Constricting the efferent arteriole

Question 33

What is the source of fibroblast growth factor 23 (FGF 23).

Answer 33

Osteoblasts and osteocytes in bone

Question 34

What is FGF23?

Answer 34

“fibroblast growth factor 23”

Question 35

What are the effects of FGF23 on the kidney?

Answer 35

1) Decreased reabsorption of phosphate

2) Decreases the production of calcitriol

Question 36

What stimulates the secretion of FGF23?

Answer 36

1) Elevated phosphate levels

2) Calcitriol i.e. active Vitamin D

Question 37

What are the relationships between FGF23 and parathyroid hormone and calcitriol and their actions?

Answer 37

Vitamin D= increased reabsorption of Ca++ & phosphate

FGF23= decreased reabsorption of Ca++ & phosphate

PTH= increased absorption of Ca++. decreased absorption of phosphate