Flashcards in Exam #4: Renal Hormones & Autacoids Deck (37):
Describe the two intrinsic renal mechanism for autoregulation of renal blood flow (RBF) & glomerular filtration rate?
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
Describe tubuloglomerular feedback for control of GFR and NaCl delivery to the distal tubule.
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
What is the role of the macula densa?
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
How can tubuloglomerular feedback help prevent excessive fluid losses if there is damage to kidney proximal tubules?
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
Give proposed reason why autoregulation is useful.
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
Can autoregulation still protect the kidney in patients with severe systemic hypertension?
No, these mechanisms stop working at the extremes of blood pressure, but very low and very high
Give the names of the autacoids/hormones which can vasodilate the afferent and efferent arterioles.
Vasodilator prostaglandins, PGE2 & PGI2 (prostacyclin)
Which hormones/autacoids cause vasoconstriction?
Explain why drugs that inhibit prostaglandin synthesis can cause renal damage.
Reduced amounts of PGE2 & PGI2 leave vasoconstriction unopposed and can lead to renal damage
What common drugs that inhibit prostaglandin synthesis?
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
Outline the renin-angiotensin-aldosterone system. Where is each produced?
Renin= juxtaglomerular cells of the kidney
ACE= lungs and kidneys
Angiotensinogen II= lung and kidneys
Aldosterone= adrenal cortex
State which cells produce most renin and how renin release is controlled.
Renin is produced by juxtaglomerular cells of the kidney and is secreted in response to decrease arterial pressure, and B1 stimulation
Which division of the autonomic nervous system innervates the cells that produce renin?
Stimulation of B1 adrenergic receptors
Outline the pathway from angiotensinogen to angiotensin II.
Angiotensin I is converted into Angiotensin II via Angiotensin Converting Enzyme (ACE)
Where do renin and angiotensin converting enzyme (ACE) act in this pathway (angiotensinogen to angiotensin II)?
Lung & kidney
Describe the effect of angiotensin II on the vascular smooth muscles.
Angiotensin II causes vasoconstriction of vascular smooth muscle
Describe the effect of angiotensin II on the adrenal cortex.
Angiotensin II increases secretion of aldosterone from the adrenal cortex
Describe the effect of angiotensin II on the efferent arteriole.
In the kidney, angiotensin II preferentially vasoconstricts the efferent arteriole b/c of the vasodilator prostaglandins and NO that act on the afferent arteriole
Describe the effect of angiotensin II on the proximal tubule Na+ reabsorption.
Increases the activity of the Na+-H+ exchanger to increase Na+ retention (and consequently, water retention)
Describe the effect of angiotensin II on the thirst center.
Describe the effect of angiotensin II on the release of ADH .
Increases secretion of ADH
Describe the effect of angiotensin II on sympathetic tone.
Increases sympathetic tone
State the two main sources of erythropoietin production. Which organ makes the most (~90%) erythropoietin?
1) Kidney= majority of EPO synthesis
What is the effect of erythropoietin on RBC production?
EPO increases RBC production
What are the major stimuli for erythropoietin secretion?
Kidney senses oxygen levels and secrets EPO when oxygen levels drop
Describe the role of the kidney in making the active form of vitamin D.
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
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?)
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
Describe the effect of parathyroid hormone on the kidney.
- 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)
Describe how chronic renal failure affects the patient’s bones.
- Chronic renal failure= low GFR & increased plasma phosphate
- Elevated phosphate increases PTH
- PTH causes bone resorption
--> "Renal Osteodystrophy"
Describe the effects of constricting either the afferent or the efferent arteriole on renal blood flow (RBF).
Afferent= decrease RBF
Efferent= decrease RBF
Describe the effects of constricting either the afferent or the efferent arteriole on GFR.
Afferent= decreased GFR
Efferent= increased GFR
How could you increase the glomerular hydrostatic pressure by constricting the efferent or afferent arterioles?
Constricting the efferent arteriole
What is the source of fibroblast growth factor 23 (FGF 23).
Osteoblasts and osteocytes in bone
What is FGF23?
"fibroblast growth factor 23"
What are the effects of FGF23 on the kidney?
1) Decreased reabsorption of phosphate
2) Decreases the production of calcitriol
What stimulates the secretion of FGF23?
1) Elevated phosphate levels
2) Calcitriol i.e. active Vitamin D