Renal Physiology Flashcards
Effect of sympathetics on renal function
- Decrease in RPF
- Decrease in GFR
- Decrease in pressure of peritubular capillary
- Increase in oncotic pressure in peritubular capillary
Filtered Load
FL = GFR * Px
Excreted Load
EL = Vu*Ux
Fractional Excretion
Fraction of filtered load of a solute that is excreted.
FE = EL/FL = (Vu*Ux) / (GFR*Px) = Cx/Ccr
If < 1 reabsorbed
If > 1 secreted
Fractional Filtration
FF = GFR/RPF
Normally about 20%
Renal Blood Flow (RBF)
RBF = RPF/(1-hematocrit)
Normally about 1000 ml/min or about 20% of Cardiac Output
ADH
Primary determinant of plasma osmolality through the control of water reabsorption or excretion in the distal nephron
- Increases permeability of CCD and MCD to water
- Increases permability of MCD to urea
- Stimulates the Na-K-2Cl pump in the thick ascending limb of the LOH
- Stimulates production of renal prostaglandins
Renin-Angiotensin II System
Primary “Low Blood Volume (low pressure) Response System”
- Causes vasoconstriction of both efferent and afferent arterioles that limits the fall in GFR relative to RBF in low volume states
- Stimulates aldosterone release
- Stimulates synthesis of vasodilatory prostaglandins
- Inhibits renin release
- Increases sodium and water reabsorption in the proximal tubule
Aldosterone
- Increases Na+ and Cl- reabsorption in the CCD and MCD
- Increases isoosmotic reabsorption of water
- Increases K+ and H+ secretion in the collecting ducts
- Primary determinant of urinary K+ excretion (balance of reabsorption and secretion)
Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP)
Part of low pressure, high blood volume response system
- Causes renal vasodilation and increases both RBF and GFR
- Increase Na+ excretion (natriuresis) and water excretion (diuresis)
Urodilatin
ANP-like hormone produced within the nephron in response to hypervolemia
- Increases Na+ excretion (natriuresis) and water excretion (diuresis)
Prostaglandins
PGE2 and prostacyclin are vasodilators that modulate RBF by antagonizing the vasoconstrictor effects of sympatheics and angiotensin II
Parathyroid Hormone
Released in response to low plasma Ca2+ concentration
- Activates calcitriol
- Increases active reabsorption of Ca2+ in the distal tubule
- Decreases proximal tubule reabsorption of phosphate (i.e., increases phosphate excretion)
Calcitriol
Most active form of Vitamin D
- Increases Ca2+ and Phosphate reabsorption
- Negative feedback on PTH release
Catecholamines
NE and EPI
- Vasoconstricts afferent and efferent arterioles (alpha-1)
- Decreases RBF and GFR
- Stimulates Na+ reabsorption in proximal tubule and LOH
- Activates renin-angiotensin system via ß1 receptors in JGA of afferent arteriole
Kinins
Vasodilators that appear to antagonize neurohumoral vasoconstriction similar to the prostaglandins
- May have role in Na+ and water handling in the collecting duct by antagonizing ADH-mediated water reabsorption
How does afferent arteriole constriciton change renal function?
Decreases GFR and RPF
How does efferent arteriole constriction change renal function?
Increases oncotic pressure and and decreases hydrostatic pressure
Increases GFR
Decreases RPF
Increases FF (GFR/RPF)
How does an increase in plasma protein concentration change renal function?
Decreases GFR, which decreases the FF
How does a decrease in plasma protein concentration change renal function?
Increases GFR, which increases FF (GFR/RPF)
What is responsible for most of renal oxygen consumption?
NaK-ATPase Pump
Which is responsible for the active reabsorption of Na+
How are the glomerular and peritubular capillaries arranged? Why is this important?
They are arranged in series.
This allows solutes and fluids filtered at the glomerulus and reabsorbed in the tubules to be reabsorbed by peritubular capillaries and returned to systemic circulation.
What is the balance of Starling forces in glomerular capillaries?
Capillary Pressure > Oncotic Pressure
Always results in filtration
What is the balance of Starling forces in peritubular capillaries?
Oncotic Pressure > Hydrostatic Pressure
Always results in reabsorption
What is the importance of autoregulation of RBF and GFR?
What accompanies this autoregulation as arterial pressure increases?
It uncouples renal function from changes in arterial pressure and ensures maintenance of renal function.
Pressure diuresis occurs when arterial pressure is increased meaning urine output is increased as a compensatory mechanism to maintain normal blood pressure
What are the mechanisms of autoregulation of GFR and RBF?
- Myogenic Vasoconstriction
- Occurs in afferent arterioles in response to sudden increases in renal perfusion pressure
- This stretches the arteriole causing vasoconstriction which reduces flow and hydrostatic pressure in glomerular capillaries
- Autoregulation of GFR is secondary to autoregulation of RBF
- Tubuloglomerular Feedback
- Macula densa provides feedback regarding flow and solute delivery (Cl-) to the afferent arteriole
- If GFR too high and increased flow, then the afferent arteriole vasoconstricts leading to a decrease in RBF and GFR
- If GFR and flow too low → vasodilation of afferent arteriole leads to increased RBF and GFR
- This also results in an increase in renin release via prostaglandin PGE2 and NO
What can override the autoregulatory mechanisms?
- Extrinsic Control
- Neural and Humoral Control
How does neural control affect RBF and GFR?
- Afferent and Efferent Arterioles are innvervated by sympathetic nerve fibers
- Low level stimulation constricts both afferent and efferent arterioles resulting in less of a decrease in GFR and RBF
- Greater stimulation causes parallel reductions in GFR and RBF
- Appears to be solely related to maintenance of arterial pressure and not the preservation of renal function (intrinsic control)
How does humoral control affect RBF and GFR?
Hormones and endogenous substances produce either renal vasoconstriction or vasodilation
- Renal Vasoconstrictors
- Angiotensin II
- Catecholamines
- ADH
- Modulate/Antagonize Constrictor Effects
- Prostaglandins
- Kinins
- Renal Vasodilation
- ANP
- Urodilatin
What is the limiting element of the glomerular filtration barrier?
Basement Membrane
What are the principal determinants of glomerular barrier permeability?
- Size and number of pores in glomerular barrier
- Presence of fixed negative charges in barrier (mainly basement membrane)
- Negatively charged glycoproteins retard the movement of negatively charged macromolecules like plasma proteins
- Nephrotic Syndrome results in a loss of these fixed negative charges
What is back-leak and how does it occur?
Back-leak is the bulk flow of water and solutes into the proximal tubule
- Occurs with afferent and efferent arteriolar vasodilation in hypervolemic states that leads to a decreased filtration fraction (GFR/RPF)
- Balance of Starling forces in peritubular capillaries become less favorabe for reabsorption, so water and solutes reabsorbed in the proximal tubule are not readily taken up into the peritubular capillaries → leads to a progressive rise in interstitial hydrostatic pressure
Hypovolemia Effects
Decreased GFR and RBF
- Arterial pressure falls
- Decreased PG and RBF
- Leading to decreased baroreceptor activity and a reflex increase in sympathetic discharge causing vasoconstriction
- Decreased PG and RBF (PG reduction less than RBF)
- Constriction of Afferent decreases PG and RBF
- Constriction of Efferent increases PG and decreases RBF
- Decreased PG and RBF (PG reduction less than RBF)
- Also occurs with increased renin release and increased circulating levels of angiotensin II
- Increased concentration of plasma proteins → increases oncotic pressure in systemic capillaries → decreases GFR
- Decreased Kf
- Mesangial contraction → reducing glomerular perfusion, decreasing surface area for filtration
- Podocytes may also contract and reduce the size of slit pores
- Efferent vasoconstriction → filtration equilibrium being reached sooner along length of glomerular capillaries
Hypervolemia Effects
Increased GFR and RBF
- Increased baroreceptor activity, which decreases sympathetic discharge to resistance vessels (limited degree of vasodilation)
- Increase in blood volume causes stretching of atria → releases ANP from atrial myocytes → ANP and urodilatin vasodilate increase GFR and RBF and increase Na+ excretion
- Intrarenal baroreceptors respond to stretch by decreasing renin release that lowers angiotensin II levels
- Increase in prostaglandins
- Increased mean arterial pressure causes small increases in PG and RBF
- Afferent and Efferent arteriole dilation → Increases RBF and PG
- Afferent dilation → Increases RBF and PG
- Efferent dilation → Decreases PG and Increases RBF
- Dilution of plasma proteins → decreased oncotic pressure in systemic capillaries
- Increase Kf
- Relaxation of mesangial cells
- Filtration equilibrium reached further along the length of the glomerular → greater capillary surface area is utilized for filtration
Clearance Equation
Cx = (Vu * Ux) / Px
What solutes can be used to estimate GFR?
Inulin
Creatinine
Renal Plasma Flow (RPF)
Clearance of PAH, which is avidly secreted by tubules, is used to estimate RPF
CPAH = RPF = (Vu * UPAH) / PPAH
*Averages 625 ml/min*
Fraction Reabsorption
FR = 1 - FE
Fraction Excretion of H2O
FEH2O = Vu / GFR = PCR / UCR
Function of the Glomerulus
- Creates ultrafiltrate of plasma
- Controls GFR
- Activation of Renin-Angiotensin-Aldosterone System (RAAS)
Proximal Tubule Function
- Isosmotic reabsorption of about 65% of filtered load of Na+, Cl-, and H2O
- Reabsorbs almost all filtered glucose and amino acids
- Reabsorbs most of filtered K+, HCO3-, Ca2+, Mg2+, and phosphate
- Secretes H+, NH3, and organic acids and bases (Some K+)
- Relatively leaky junctions allow diffusion of solutes via paracellular route
- Fluid leaving is isotonic to plasma
Loop of Henle Function
- Reabsorbs about 20% of the filtered load of Na+ and water
-
T__hin descending limb permeable to water
- Larger amount of solute is reabsorbed in ascending limb → net solute reabsorption in loop is greater than water reabsorption
- Fluid leaving is hypotonic to plasma
-
Thin Ascending Limb
- __Impermeable to water
- Permeable to Na and Cl
- Contains a urea transporter (moves urea into tubule down concentration gradient)
-
Thick Ascending Limb is impermeable to water (diluting segment)
- Allows for formation of steep osmotic gradient b/t tubule and interstitium - countercurrent multiplier
- Na+, K+, and Cl- actively reabsorbed in thick ascending limb (Na-K-2Cl co-transporter) → hypertonic interstitium
- Increases driving force for water reabsorption from thin descending limb and medullary collecting ducts
- Excess Na+ and Cl- are removed from the medullary interstitium by vasa recta
Distal Nephron Function
- Fine tunes urine volume and solute concentration as 85% of water and solutes are already absorbed
- Consists of:
- Distal Tubule
- Cortical Collecting Tubules
- Medullary Collecting Ducts
Distal Tubule Function
- Reabsorbs small fraction of filtered Na+ and Cl-
- Site of active control of Ca2+ reabsorption and excretion
Cortical Collecting Tubules Function
- Principal Cells
- Reabsorb Na+ and Cl-
- Secrete K+ (aldosterone sensitive)
- Intercalated Cells
- Secrete H+
- Reabsorbe K+
- Secrete HCO3- in metabolic alkalosis
- Reabsorb water in presence of ADH
Medullary Collecting Ducts Function
- Reabsorbs Na+ and Cl- (aldosterone sensitive)
- Inhibit tubular reabsorption of Na+ (ANP and BNP sensitive)
- Water and Urea reabsorption (dependent on ADH levels)
- Secrete H+ and NH3
- Can either reabsorb or secrete K+
Where does reabsorption of glucose occur?
Proximal Tubule Only
Where are organic solutes (glucose, amino acids, etc.) reabsorbed?
Proximal Tubule
How is most glucose reabsorbed?
Na+-Glucose Symporter driven by NaK-ATPase Pump
What is the energy source driving the Na-Glucose symporter?
The electrochemical gradient for Na+ generated by NaK-ATPase Pump