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What are the 3 functions of the kidney?
Regulatory (acid/base, ionic, extracellular fluid volume, reabsorption/excretion)EndocrineExcretory TERM 2
What is the effect of renin? Define RAS
DEFINITION 2 It activates circulating angiotensin I (then converted to angiotensin II) and causes vasoconstrictionRAS = renin- angiotensin system TERM 3
What molecule do the kidneys secrete that
controls production and secretion of red blood
cells?
DEFINITION 3 Erythropoietin (controls erythropoiesis)85% of total erythropoietin produced at kidneys TERM 4
What cofactor is converted into active
metabolites in the kidney?
DEFINITION 4 Vitamin D (important in Ca2+ and PO4,3- metabolismAt renal proximal tubules (and skin) TERM 5
Define micturation
DEFINITION 5 the act of urination
What will happen if you can't excrete uric
acid?
You will get gout (build up in joints) TERM 7
Why is urine yellow? Where does the smell
come from?
DEFINITION 7 Due to urochrome and urobilinOdour is due to ammonia (asparagus from asparagine) TERM 8
Label the kidney. Where are the colums of
Bertin?
DEFINITION 8 1 - renal pelvis2 - ureters3 - urinary bladder4 - ureter5 - renal pelvis6 - renal pyramids7 - renal cortex8 - renal medullaColums of Bertin are the part of the cortex which extends between the renal pyramids TERM 9
Why is the right kidney slightly lower than the
left?
DEFINITION 9 Because of the liver TERM 10 DEFINITION 10 see next slide
What is the juxtaglomerular
apparatus?
Where the tubule (end of TAL and beginning of DCT) makes contact with originating glomerulus; involved in tubuloglomerular feedback mechanism for autoregulation of renal blood flow and glomerular filtration rateContains macula densa (between afferent and efferent arterioles) involved in sensing tubular flow and ionic concentrationContains juxtaglomerular/granula cells (in afferent arteriole wall close to glomerulus) that secrete reninContains extraglomerular mesangial cells (involved in support and signalling) TERM 17
Describe the flow of blood into and out of the
kidney. How does the blood flow in
juxtamedullary nephrons differ from cortical
nephrons?
DEFINITION 17 renal artery -- afferent arterioles -- bowman's capsule (capillary network aka tuft) -- efferent arteriole -- peritubular capillaries (branches out and surrounds tubular segments; carry reabsorbed water and electrolytes back to circulation) -- renal veinin juxtamedullary nephron, the peritubular capillaries are extended (called vasa recta) and form hairpin loops next to the Loop of Henle TERM 18
What is the main innervation of the kidneys?
What can innervation control?
DEFINITION 18 Mainly sympatheticTarget vasculatures = vasoconstriction via adenoreceptor alphaTarget PT/TAL/Distal nephron = increase Na+ reabsorption via adenoreceptor alpha and betaTarget juxtaglomerular (granular) cells = secretion of renin via beta adenoreceptor TERM 19
What percentage of cardiac output
constitutes the renal blood flow?
DEFINITION 19 20-25% of cardiac output passes through the kidneys TERM 20
What is the normal renal blood flow rate?
DEFINITION 20 3-5 mL/min/g of tissue or 1-1.2 L/min for both kidneys
Why does the inner medulla have a lower
blood flow rate?
This is because it has fewer capillaries TERM 22
Define clearance
DEFINITION 22 Volume of plasma that is completely cleared of substance X per unit timeCan be used to estimate renal plasma flow and glomerular filtration rateRatio of excretory rate of substance X and its plasma concetration:Cx = (Ux)(V)/(Px)Ux = urinary [x] (mg/mL)V = urinary flow rate (mL/min)Px = plasma [x] (mg/mL)UxV = urinary excretory rate of X (mg/mL) TERM 23
What substance is used to estimate renal
plasma flow via clearance? Why is it used?
DEFINITION 23 Para-aminohippuric acid (PAH)It is used because it is almost completely cleared by the kidneys (doesn't re-enter the blood) TERM 24
Describe the theory behind using clearance to
estimate renal plasma flow
DEFINITION 24 Based on Fick's principle of conservation of mass; the rate of a substance moving into the kidneys equals the sum of the rate of the substance moving out and being taken up by the kidneys. The kidneys only filter plasma so the calculation is only used for plasmaInput of X = Output of X + Taken up X(RPF)(Px arterial) = (RPF)(Px venous) + V(Ux)PAH is almost completely cleared so (RPF)(Px venous) = 0RFP = (Upah)(V)/(Ppah) = Cpah TERM 25
What is the one drawback of using PAH for
renal plasma flow estimation? What is the
estimate of RPF?
DEFINITION 25 PAH is almost completely cleared, but some remains (not 100% cleared) so the RPF measured using PAH clearance is referred to as the "effective" RPFEstimated RPF = 625 mL/min
What constitutes ultrafiltrate?
Filtrate generated by the glomerulus; ionic composition similar to plasma except with negligible amounts of macromolecules (proteins, lipids) TERM 32
How are glomerular capillaries able to be so
permeable and maintain shape?
DEFINITION 32 Mesangial cells likely provide support for capillary network TERM 33
What role do mesangial cells play in control of
GFR?
DEFINITION 33 Mesangial cells can contract and relax to increase or decrease filtration surface and therefore GFR TERM 34
What barriers does ultrafiltrate have to pass
between capillary lumen and Bowman's space
of glomerulus?
DEFINITION 34 Glomerular capillary endothelium - has fenestrations (slits) through which filtrate can pass but large molecules cannotGlomerular basement membrane - collagen and proteoglycans but no cellsPodocyte pedicles (legs that wrap around capillaires) aka epithelial cells - have filtration slits (aka diaphragm) between pedicles TERM 35
What kind of molecules are filtered out of the
plasma? Do any of them have an easier time
at it?
DEFINITION 35 Radii less than 15 AMolecular weight less than 5000 DaCations move through the barrier easier b/c the membane is lined with negative chargesNeutral molecules move though second easiestAnions move through with the most difficulty
Why is the filtration barrier membrane lined
with negative charges?
To repel proteins (which are normally negatively charged) so as to not have them get stuck the the filtration barrier and block filtration TERM 37
What criteria must a substance meet to be
used to estimate GFR? What molecule is
used?
DEFINITION 37 Freely filtered, doesn't alter GFR, not produced by the kidney, not metabolized by the kidney, not reabsorbed or secreted by the nephron, not toxicInulin is used; estimate GFR using the clearance (NOT 100%, some flows back to system) of insulin b/c inulin is only filtered by the nephron and filtered inulin is exreted into the urin so filtration rate of inulin = excretory rate of inulinCreatinine clearance could also be used TERM 38
What other method is there for estimating
GFR? Describe it
DEFINITION 38 Starlings forces: the movement of fluid across a capillary membrane is governed by the balance of oncotic pressure and hydrostatic pressure across the membrane4 forces:Pgc = glomerular cap hydrostatic P --> force water out of cappi(gc) = glomerular cap oncotic pressure --> draws water into capPbs = hydrostatic P of bowman's space --> force water into cappi(bs) = oncotic P of bowman's space --> draws water out of cap TERM 39
Why is pi(bs) = 0 when using Starlings forces
to estimate GFR?
DEFINITION 39 It's 0 b/c oncotic pressure is generated by macromolecules, of which there are none in the bowman's spacehydrostatic pressure is generated by water, though so P(bs) isn't 0 TERM 40
What is the equation for ultrafiltration
pressure? What is starling's equation? How
does this related to GFR?
DEFINITION 40 Puf = Pgc - Pbs - pi(gc)in mmHgq (rate of fluid movement across capillary) = Kf * Pufwhere Kf is filtration coefficient depending on the filtration SA and memrbane permeabilityGRF = Kf*Puf
Via which pathway are solute and water
transported into the peritubular space?
Paracellular (between cells) or transcellular (across cells) pathway TERM 47
What kind of transporter for sodium is on the
basolateral/peritubular membrane?
DEFINITION 47 Na/K ATPase TERM 48
What is the difference between apical
transmembrane, basolateral transmembrane
and transepithelial potential differences?
DEFINITION 48 Apical transmembrane PD = PD between lumen and inside of cellsBasolateral transmembrane PD = PD between peritubular space and inside of cellTransepithelial PD PD between luminal and pertitubular spaces TERM 49
Why is the maintenance of Na+ plasma
concentration important?
DEFINITION 49 It is the major electrolyte in maintaining ECFV and plasma osmolality TERM 50
Add percentages
DEFINITION 50 see next slide
see back for detail
Approximately 2/3 of the filtered Na+ and water are reabsorbed in the PT.Water reabsorption is usually a consequence of increased osmotic gradient resulting from Na
- transport (osmosis).ATL and TAL of Loop of Henle are referred to as the diluting segment since they are impermeable to water (tight tight junction). TERM 52
What hormones control Na+ reabsorption?
DEFINITION 52 ADH (antidieuretic hormone) stimulates Na+ reabsorption in the TALAldosterone increases reabsorption of Na+ in late DT and CD TERM 53
What hormones control H2O reabsorption?
DEFINITION 53 ADH (antidieuretic hormone) acts on basolateral V receptors = increase water permeability in DT and CD by increasing insertion of water channels (aquaporin 2) into apical membraneH2O also follows Na+ gradient (more sodium in peritubular space = more H2O travel through leaky junctions of PT) TERM 54
How can you tell if water will enter the
capillary or leak back into the lumen from the
peritubular space?
DEFINITION 54 Starlings forcesq = KfPuf = Kf(Pps - Ppc + Pipc)Pps = hydrostatic pressure of peritubular spacePpc = hydrostatic pressure of peritubular capillaryPi pc = osmotic pressure of peritubular capillary TERM 55
What is different between the water
movement in the PT and DT/CD?
DEFINITION 55 Proximal tubule: osmotic H2O movement (apical and basolateral membrane have aquaportin 1)Distal tubule/collecting duct: ADH mediated H2O movment (aquaporin 2 on apical membrane; aquaportin 3 and 4 on basolateral)
How is sodium reabsorbed along the
TAL?
Na/K/2Cl cotransporter (major): side effect of build up of intracellular K in intracellular space (Na/K pump and this transporter) = leak K into lumen = more positive lumen = easier for cations (ie. Mg) to cross into peritubular space via paracellular pathway down electrochem gradientNa/H exchanger TERM 62
How is sodium reabsorbed along the
DT?
DEFINITION 62 Na/Cl symporter TERM 63
How is sodium reabsorbed along the late late
DT and CD?
DEFINITION 63 2 types of epithelial cells in late DT/CD: intercalated (alpha and beta) cells and principal cellsPrincipal cells = H2O and Na reabsorption via epithelial sodium channel (aldosterone increases Na reabsorption by increasing opening prob, activity and membrane insertion of these channels) TERM 64
What part of the nephron controls overall
renal handling of K?
DEFINITION 64 Distal nephron (DT and CD); secrete excess K during normal/increased K intake; reabsorption during K depletion TERM 65 DEFINITION 65 see next slide
How is K secreted in the distal
nephron?
Increased plasma concentration of K = more K enters "principal" renal epithelial cells from paracellular space (?) = secreted by K channel and Na reabsorbed to maintain electroneutralityAlso secreted through K/Cl cotransporter TERM 67
What can enhance secretion of K?
DEFINITION 67 increased transepithelial potential difference (lumen is more negative)Increased aldosterone secretion induced by increase in plasma K concentration (stimulates K reabsorption = more K to be secreted)Increased tubular flow rate (wash out secreted K from secreted site = more favorable electrochem gradient = more K secreted) TERM 68
How is K
reabsorbed?
DEFINITION 68 Reabsorbed in alpha-intercalated cells by H/K-ATPase then passively into pericellular space (during K depletion) TERM 69
Why is the excretion of K less than 1% in K
depletion but 15-80% in normal cells?
DEFINITION 69 Because the distal tubule/collecting duct will absorb rather than secrete K under depeletion conditions TERM 70
What two organs control homeostatic control
of acid-base balance?
DEFINITION 70 Kidneys and lungs
What is the henderson hasselbalch equation?
pH = pKa + log (A-/HA)where pKa is the dissociation constant of a particular acid TERM 77
What is the chemical equation for the
bicarbonate system?
DEFINITION 77 H2O + CO2 <---CA---> H2CO3 <-----> H+ + HCO3-where CA is carbonic anhydrase TERM 78
Define Henry's Law
DEFINITION 78 The solubility of a gas in solution at a given temperature is directly proportional to its partial pressure in equilibrium with a the particular liquidThis allows us to transform the Henderson-Hasselbalch equation to relate to HCO3 and CO TERM 79
What does the Henderson-Hasselbalch
equation look like according to Henry's Law?
DEFINITION 79 see next slide TERM 80
see back for details
DEFINITION 80 If the log ratio is maintained at 20:1, the pH will always be 7.4 (given pKa of the buffering system is constant)Plasma CO2 concentration maintained by respiration, plasma HCO3- maintained by reabsorption of filtered HCO3- and generation of new HCO3-NOTE: PO2 should be PCO
What causes respiratory acidosis? What is the
compensatory response?
Increased PCO2 (ie. by hyperventilation)Compensate by renal retention/creation of HCO3- TERM 82
What causes metabolic alkaosis? What is the
compensatory response?
DEFINITION 82 Low H+ (or high HCO3) (ie. by vomiting, nasogastric suction and dieuretic therapy)Compensate by decreasing alveolar ventilation ie. hypoventialtion (less ventilation) = increase PCO TERM 83
What are the 4 ways the kidneys can
maintain acid-base balance?
DEFINITION 83 Reabsorption of filtered HCO3Generation of new HCO3 by formation of titratable acid and NH4+Excretion of H as salts of titratable acids and NH4+Secretion of HCO3 under extreme conditions TERM 84
How much HCO3 is usually reabsorbed by the
kidney? How do you calculate filter load?
DEFINITION 84 99% is reabsorbed (85% in PT, 10% in TAL, 5% in CD); amount reabsorbed depends on filter load = GRF*P(HCO3)Decreased filter load = increased pH = decrease in PCO TERM 85
Is it the same HCO3 from the lumen that
enters the capillary?
DEFINITION 85 No, HCO is converted into CO2 in the lumen and enters the cell by diffusion before being converted back into HCO3Also results in excretion of 1 H+
What is the pathway of antidieuretic
hormonecontrol on plasma osmolality?
see next slide TERM 92
note on back
DEFINITION 92 AVP (arginine vasopressin) = ADH TERM 93
What is the normal urinary output for adults?
DEFINITION 93 1.5L/day (1ml/min) but varies depending on state of hydration and substances ingested TERM 94
What is the range of osmolality in
concentrated urine?
DEFINITION 94 40 - 1400 mosmol/kg H2O TERM 95
How do you calculate the minimal amount of
urine that needs to be excreted each day?
DEFINITION 95 Solutes excreted each day: 650 mosmolMaximal osmolality achieved = 1400mosmol/kg H2O650/1400 = 0.5 L per day = obligatory urine output
What is urine osmolality compared against to
deterine if its iso, hypo or hyerosmotic?
Plasma osmolalityDilute = hyposmotic = Uosm < PosmConcentrated = hyperosmotic = Uosm > PosmIsosmotic = U = P TERM 97
Define osmolar clearance
DEFINITION 97 volume of plasma that is completely cleared of osmotically active subtances per unit timeCosm = Uosm*V/Posm TERM 98
Define solute free water clearance
DEFINITION 98 CH2O: used to quantify how dilute the urine is supposed to be; is the volume of plasma that is completely free of solutes per unit timeRepresents distilled water (solute free) that is required to be added to an isomotic urine to render it diluteClearance equation doesn't apply here!CH2O + Cosm = VIf CH2O is negative = solute- free water reabsorption (volume need to be be reabsorbed to render urine concentrated) TERM 99
Where is solute free water reabsorption
generated?
DEFINITION 99 at the CD (due to ADH) TERM 100
What kind of receptors measure extracellular
volume?
DEFINITION 100 ECFV includes volume in vasculature and interstitiaVolume receptors in cardiovasculature system sense 8-15% changes via stretch (respond to pressure)= baroreceptors at atria/veins (low pressure) and carotid sinus/aortic arch (high pressure)
