GFR and GFR Regulation Mechanisms Flashcards
True or false GFR is slightly larger in males
True
True or false homeostasis requires a near constant GFR
True
What would happen if GFR was too fast
filtrate in the tubules may pass too quickly and substances may not be reabsorbed
What would happen if GFR was to slow
filtrate in the tubules may pass too slowly and all substances may be reabsorbed and waste may not be excreted efficiently
How does renal blood flow (RBF) affect GFR
RBF indirectly determines GFR by:
- modifying rate of solute and water reabsorption by the proximal tubule
- participates in changing concentration of urine
- delivers O2 nutrients and hormones to the nephrons
- delivers waste for excretion
How does constriction of afferent arteriole affect RBF and GFR
decrease RBF and GFR
How does dilation of afferent arteriole affect RBF and GFR
increases RBF and GFR
How does constriction of efferent arteriole affect RBF and GFR
decreases RBF but increases GFR
How does dilation of efferent arteriole affect RBF and GFR
increase RBF but decreases GFR
What GFR is considered stage 1 CKD
GFR normal but protein in the urine
What GFR is considered stage 5 CKD
GFR <15
What is needed to calculate GFR
Serum creatinine, age, race, wt, gender
Why is creatinine used to calculate GFR
It is a waste product from normal muscle breakdown that is neither metabolized nor reabsorbed in the kidneys (so freely peed out). In healthy adults the serum level of creatinine should equal the urine creatinine clearance
-if serum level is high, than urine levels/clearance are low because the kidney is not filtering properly
What are the 3 mechanisms that regulate GFR
- Renal autoregulation
- Neural regulation
- Hormonal regulation
Renal auto regulatory mechanisms of GFR are constant between what BP
90-180 mmHg
What is the target of most renal auto regulation mechanisms
variable changes in resistance of afferent arterioles
What are the 2 renal autoregulation mechanisms and what do they respond too
- Myogenic mechanism =respond to change in BP
2. Tubuloglomerular = respond to changes in Na-CL H2O
Describe the myogenic mechanism of renal autoregulation
- BP increase causes stretch in afferent arteriole
- Causes brief increase in RBF and GFR
- Smooth muscles of afferent arteriole contract briefly reducing RBF and GFR , this helps to preserve nephron integrity
- afferent arterioles then adjust resistance to normalize GFR
Below 90 mmHg or above 180 mmHg does autoregulation occur
No, it is absent
Describe juxtaglomerular apparatus
a complex structure composed of juxtaglomerular cells (granular cells), macula densa cells, Lacis cells (extraglomerular mesangial cells) that has the ability to affect systemic BP through the tubuloglumerular feedback
Where are juxtaglomerular (granular) cells located and what do they do
Located in the afferent arterioles
They are modified smooth muscle cells that:
- detect low BP (via lack of stretch)
- synthesis/store/secrete Renin
Where are macula densa cells located and what do they do
Located in ascending loop of henle were it meets the afferent arteriole
They:
- Detect increase NaCL in the filtrate
- When they sense increased solute concentration (meaning high GFR) they release ATP and adenosine which causes contraction of afferent arteriole and extraglomerular mesangial cells
Where are extraglomerular mesangial cells located and what do they do
Located between the afferent arteriole, efferent arteriole, and late thick ascending loop of henle
Receive signals from other juxtaglomerular apparatus cells and contract or relax as told to
Describe tubuloglomerular feedback
- When GFR increases, rate of filtrate through the tubules increase and reabsorption of Na, Cl, and H20 decrease
- Macula densa cells sense this increased concentration of Na and CL in the filtrate and release ATP and adenosine
- Extraglomerular mesangial cells, glomerular mesangial cells and the afferent arteriole wall cells react to the ATP and adenosine and constrict which lowers RBF and GFR to normal levels
What happens to renal autoregulation when there are large blood pressure or extra cellular fluid volume changes
Hormonal and neural systems play a larger role in GFR regulation, autoregulation can play a role but it is not the key player any more.
True or false blood vessels of the kidneys are supplied by the sympathetic and parasympathetic nervous system
False, blood vessels in the kidney (and else where in the body) are only supplied by the sympathetic nervous system.
What happens when there is greater sympathetic stimulation throughout the whole body
- Sympathetic stimulation causes EP and NE to be released from adrenal medulla
- NE/EP caused afferent arteriole vasoconstriction and reduced RBF because this blood is needed else where
- GFR is reduced until autoregulation kick in and normalizes GFR
Describe the action of secretion and the hormonal effect of Natriuretic peptide (ANP/BNP)
Secreted by atria or brain in response to increased volume
Effects:
- Dilate afferent arterioles and constricts efferent arteriole
- Inhibits reabsorption of Na and H2O in the distal convoluted tubules and collecting ducts (so more filtrate is excreted)
- Inhibits RAAS
Describe the action of secretion and the hormonal effect of prostaglandins
Secreted only in response to local hemorrhage or reduced extracellular fluid volume
Attempts to counteract vasocontraction of the sympathetic nervous system and Angiotensin II in order to prevent renal ischemia
Do prostaglandins effect GFR
No prostaglandins cause a small change in RBF but not enough for GFR
Describe the action of secretion and the hormonal effect of nitric oxide
Causes vasodilation at afferent and efferent arterioles
Secreted from the endothelium to counteract vasoconstriction of angiotensin II and certain catecholamines
Describe the hormonal effect of bradykinin
Vasodilator that stimulates release of nitric oxide and prostaglandins
Describe the action of secretion and the hormonal effect of endothelin
Potent vasoconstrictor at both afferent and efferent arterioles
Released by endothelial cells of renal vessels, mesangial cells, and distal tubular cells in response to angiotensin II and EP
Describe the action of secretion and the hormonal effect of adenosine
Released by macula densa cells of the juxtaglomerular apparatus in tubuloglomerular feedback autoregulation
Causes vasoconstriction of afferent arteriole
What are the 3 ways the RAAS activated
All 3 causes Renin to be released
- When there is low perfusion/afferent arteriole pressure
- Beta 1 adrenergic receptors at the juxtaglomercular cells are stimulated
- Decrease in Na in the tubule system causes macula dense cells to release ATP/adenosine and start tubuloglomerular feedback
Once renin is released describe the actions leading to Angiotensin II activation
- Renin finds angiotensinogen (protein produced in the liver and regularly released in the blood stream ) and cleaves off a 10 AA peptide converting it to Angiotensin 1
- Angiotensin 1 is converted to Angiotensin 2 by angiotensin converting enzyme (ACE) in the lungs and the kidneys
What are the functions of Angiotensin II
- Vasoconstrictor that effects both the afferent and efferent arterioles (minor vasoconstriction at efferent first at lower levels then stronger vasocontraction of afferent at higher levels )
- Enhances reabsorption of Na, CL, H2O at proximal convoluted tubules
- Stimulates the adrenal cortex to release Aldosterone
- Stimulates release of ADH
What is the effect of aldosterone on the nephron
Causes principle cells in the collecting ducts to reabsorb Na (water follows) and secrete more K
What is the effect of ADH on the nephron
Causes principle cells in the distal convoluted tubules and collection ducts to generate more aquaporin 2 channels in the apical membrane, which causes these cells to become permeable to H2O allowing more H2O to be reabsorbed
What are ACE inhibitors used for and how do they work
Used for primary HTN
Work by blocking conversion of Angiotensin 1 to Angiotensin 2 . They also increase bradykinin levels which causes vasodilation which increases GFR and offloading extra fluid
What is a side affect of ACE inhibitors
Increased bradykinin levels caused by the Rx can cause a characteristic dry cough in some pts
What are Angiotensin 2 receptor blockers used for and how do they work
Used to treat HTN, used as a 2nd line treatment to ACE inhibitors
Blocks binding of Angiotensin 2 at receptors
