Term
What do each of the following terms mean and what are their normal levels?
1) Renal Blood Flow (RFR)
2) Renal Plasma flow (RPF)
3) Glomerular FIltration Rate (GFR)
4) Filtration Fraction |
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Definition
1) Blood that perfuses both kidneys each minute (1200 ml/min)
2) Plasma that perfuses both kidneys each minute/normally 55-60% of RBF) (670 ml/min)
3) Volume of plasma filtered each minute by glomeruli (125 ml/min for males and 100 ml/min for females)
4) GFR:RPF ratio (normally 0.18-0.22)
*GFR and RPF must maintain nearly constant flow to maintain equilibrium** |
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Term
| What factors determine renal blood flow distribution? |
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Definition
Pre-glomerular
1) Size of glomeruli (larger juxtaglomerular get more blood than superficial)
**More salt intakes increases BF to superficial glomeruli with shorter LOH, in order to increase solute excretion**
Post-glomerular
2) 85% goes to cortex
3) 15% goes to medulla |
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Term
| What happens to Pre-glomerular blood flow following a high-salt meal? |
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Definition
| More salt intake increases BF to superficial glomeruli with shorter LOH (vs. Juxtaglomedullary glomeruli with long LOH in order to increase solute excretion |
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Term
1) How does the starling principle relate to GFR?
2) How is GFR affected by constriction of afferent and efferent arterioles?
3) How might Kf be manipulated? |
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Definition
The amount of plasma filtered each minute depends upon the balance hydrostatic and oncotic pressures in the glomeruli
1) GFR= Kf [(Pgc-Pb)- (Ogc-Ob)
Where (Pgc-P) indicates the hydrostatic pressure differential in the glomerular space and (Ogc-Ob) indicates the oncotic pressure differential.
If hydrostatic pressure differential dominates, then GFR will increase.
2a) Afferent constriction (pre-glomerular) increases afferent arteriolar resistance and reduces RBF, glomerular capillary hydrostatic pressure and GFR
2b) Efferent constriction (post-glomerular) increases efferent resistance, increasing glomerular hydrostatic pressure and GFR, while decreasing RBF
3) Kf is determined by the product of (total filtering SA of the glomerulus) (hydraulic conductivity of the glomerular membrane)
- Relaxing mesangial cells would increase Kf, thereby increasing GFR |
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Term
What happens to GFR and RBF during afferent arteriolar dilation?
What about during efferent arteriolar constriction?
Mesangial cell constriction? |
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Definition
1) Pre-glomerular resistance decreases, increasing RBF, capillary hydrostatic pressure and GFR.
2) Post-glomerular resistance increases, increasing capillary hydrostatic pressure and GFR, while decreasing RBF
3) Decreased Kf (surface area of filtration), so decreased GFR. |
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Term
| Where does the majority of autoregulation of renal vascular resistance occur? |
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Definition
In pre-glomerular, "afferent" arterioles.
**Critical function of juxtaglomerular apparatus, in order to prevent excessive salt/water loss in distal nephron** |
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Term
| Describe the concept of "effective circulating volume" |
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Definition
Maintained by tight control of GFR and reabsorption by kidney
"The volume necessary in the vascular space to ensure adequate vital organ perfusion" |
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Term
What do each of the 4 renal disease have in common?
1) Acute Kidney injury
2) Diabetic Nephropathy
3) HTN Nephropathy
4) Progressive renal failure (hyperfiltration injury) |
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Definition
| All caused by autoregulatory failure! |
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Term
What is the "Myogenic Hypothesis" of Autoregulation?
How does it relate to Tubuloglomerular feedback (TGF) |
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Definition
1) Afferent arterial smooth muscle contracts/relaxes with wall tension in a calcium-dependent manner
**increased wall tension causes compensatory contraction**
2) Macula densa detects changes in Cl- delivery and modulates juxtaglomerular vasoconstriction accordingly via adenosine binding to AT1 receptors in afferent arterioles (ATP-hydrolysis increases adenosine levels)
** increasing RBF increases GFR and delivers more chloride to cTAL, so macula densa cells cause vasoconstriction in afferent arterioles to increase pre-glomerular resistance and decrease GFR and RBF to normal levels ** |
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Term
| How does the renin-angiotensin system extrinsically regulate renal blood flow and glomerular filtration? |
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Definition
Preserve GFR during low perfusion states when RBF cannot be maintained.
1) When intravascular volume is low, renin is secreted from granular epithelial cells of afferent arterioles into the surrounding interstitium.
2) Renin cleaves Angiotensinogen to Ang-1 and ACE converts Ang-1 to Ang-2.
3) Ang-2 circulates and binds to AT-1 receptor causing Systemic Vasoconstriction (afferent arterioles, efferent arterioles AND mesangial cells), increasing Systemic BP and Renal Perfusion Pressure
5) Decrease in RBF and GFR (less than RBF), thereby increasing the FILTRATION FRACTION
**constriction is more prominent in efferent arterioles**
6) Stimulate aldosterone release, proximal tubular sodium absorption, thirst, ADH release and sympathetic nerve activity |
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Term
| What are 4 causes of renin release from JG apparatus (afferent arterioles) into the interstitium? |
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Definition
All caused by decreased intracellular calcium leading to increased cAMP levels in JG cells
1) When renal artery perfusion pressure decreases, renal vascular baroreceptor in JG cells senses arteriolar wall tension change
2) When afferent arteriolar, carotid arterial and atrial wall tension decreases, vascular baroreceptors activation sympathetic nervous system to release catecholamines.
3) Decreased sodium intake
4) renal sympathetic nerve activity increases |
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Term
| What chemicals can inhibit renin release? |
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Definition
1) Ang 11 itself
2) Potassium
3) ADH
4) Thromboxane A2 (platelet accumulation) |
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Term
| How can the RAAS system preserve GFR despite decreasing RBF? |
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Definition
Although Ang-2 binding to AT-1 receptor causes systemic vasoconstriction (especially of post-glomerular arterioles), the decrease in RBF is MORE than the decrease in GFR.
Therefore, Filtration Fraction INCREASES (you get more bang for your buck when blood flow cannot be maintained) |
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Term
| How does PGE signaling extrinsically regulate renal blood flow and glomerular filtration? |
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Definition
1) PGE synthesis and release is promoted by vasoconstriction , volume depletion and renal hypoperfusion (Ang2, BDK, catecholamine, ADH and Glucocorticoids).
2) Act directly on afferent arteriolar smooth muscle (vasodilation) and indirectly via neurohormonal regulation.
This vasodilation increases RBF and GFR (battling against systemic vasoconstriction from RAAS system during effective volume depletion, and limiting the constriction to the efferent arterioles, which actually will increase RBF and GFR). |
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Term
| What will happen to a patient in effective volume depletion who is given aspirin and NSAIDs |
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Definition
These drugs will inhibit PGE, preventing afferent arteriolar vasodilation.
There will be unopposed vasoconstriction from RAAS and renal function will be compromised as GFR and RBF fall (WATCH OUT!) |
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Term
| What are the major neural mechanisms of extrinsic regulation of renal blood flow and glomerular filtration? |
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Definition
** NOT normally necessary for efficient autoregulation or tubuloglomerular feedback and MOST important in stressful condition**
1) Adrenergic fibers for SNS increase renal vascular resistance.
**High levels of alpha-stimulation cause predominant effect on afferent arterioles and decrease glomerular capillary pressure, decreasing RBF and GFR**
2) Stimulation of renal efferent nerves increases renin releases and PGE formation. |
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