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46 Cards in this Set

  • Front
  • Back

roles of kidney

-blood filtration


-excretion of endogenous and exogenous compounds


-endocrine fxns

filtration capacity of kidney

-clear waste by excretion into urine, returning essentials back ino blood


-filter 125ml/min (180L/d)


-make 1mL/min urine


-receive 20% of CO from a pair of renal arteries arising from abdominal aorta


-renal arteries become afferent arterioles


-each kidney made up of ~1 million nephrons, each capable of forming urine

structure of nephron

2 major components:


a) glomerulus


b) long tubule

glomerulus

glomerular capillaries surrounded by Bowman's capsule


-through which large amounts of fluid are filtered from the blood (the glomerular capillaries are supplied w blood by afferent arteriole while blood leaves via efferent arteriole)

tubule

proximal tubule, loop of henle, distal tubule, collecting tubule


-in which filtered fluid is converted into urine

2 capillary beds of renal circulation

glomerular (afferent arteriole ends in the capillaries of the glomerulus where high pressure causes filtration)


and


peritubular (efferent arteriole ends in the peritubular capillary network where low pressure permits absorption)

processes by which substances excreted in the urine:

1) glomerular filtration


2) reabsorption of substances from the renal tubules into the blood


3) secretion of substances from the blood into the renal tubules




urinary excretion rate = filtration rate - reabsorption rate + secretion rate

what happens after blood enters afferent arteriole?

-filtration from glomerular capillaries into bowman's capsule of large amount of fluid


-glomerulus behaves like a sieve; fluid is filtered; cells and proteins remain



layers of glomerular capillary membrane

similar to that of other capillaries, except that it has 3 (instead of 2) major layers:


endothelium


-perforated by thousands of small holes called fenestrae


basement membrane


-meshwork of collagen and progeoglycans


-main filtration barrier


-primary restriction point for plasma proteins


epithelial cells (podocytes)


-have long "foot-like" processes that wrap around capillaries leaving gaps called split pores




these layers make up filtration barirer

what happens after fluid leaves the Bowman's capsule?

-passes through tubules, modified by reabsorption of water and specific solutes back in to the blood (active and passive transport depending on substance and site) or by secretion of other substances from the peritubular capillaries into the tubules


-blood exits through the efferent arteriole

GFR

the amount of fluid which leaves the glomerular capillaries to go into the glomerular space



regulated by constriction or dilation of afferent arterioles

tubular reabsorption

quantitatively more important than tubular secretion in the formation of urine


-highly selective




-some substances (eg glucose, aa) almost completely reabsorbed from tubules so urinary excretion rate = 0


-certain waste products (eg urea, creatinine) poorly reabsorbed from tubules and excreted in large amounts




therefore, by controlling rate at which they reabs diff substances, kidneys regulate excretion of solutes (essential for precise control of composition of body fluids)

tubular secretion

some substances secreted into the tubular fluid for removal


eg. K+, H+, urea, some drugs like thiazides

juxtaglomerular cells

specialized set of smooth muscle cells that line the afferent and efferent arterioles

mechanisms that control JGC release of renin

1. direct pressure sensing mechanism within the afferent arteriole (decreased tension increases renin release likely a consequence of prostaglandin secretion)


2. sympathetic innervation of JGC promotes renin release via beta1-adrenergic signaling


3. specialized cells within distal tubule called macula densa that is especially sensitive to electrolyte concentration (esp NaCl)


-decreased luminal NaCl delivery (causes secretion of adenosine) increases JGC renin release (adenosine also dilates afferent arteriole)

renin

protease produced and secreted by JGC


-cleaves circulating angiotensinogen (large plasma protein) formed by the liver to the decapeptide angiotensin I (ATI)

ACE

highly expressed in pulmonary vascular endothelium, but also present in endothelial cells lining the coronary arteries and blood vessels in the kidneys


-cleaves angiotensin 1 to the active octapeptide angiotensin II



fxns of ATII

1. stimulation of aldosterone secretion from the adrenal cortex


2. arterial vasoconstriction


3. can also stimulate thirst and ADH (vasopressin) secretion

aldosterone

promotes renal tubular reabsorption of NaCl

vasopressin

can increase peripheral vascular resistance and thus BP by acting on the V1 receptor


-can also promote absorption of water (stimulates the V2 receptor in the cells of the collecting duct)


-as a consequence, aquaporin (sepcifically A!2) or water channels are translocated to the plasma membrane and water is absorbed into the blood


-increase intravascular volume and BP

tubular reabsorption mechanisms

includes passive and active mechanisms


-simple diffusion


-channel-mediated diffusion


-carrier-mediated (facilitated diffusion)


-counter transport


-ATP-mediated transport

simple diffusion

solutes w sufficient lipid solubility may diffuse across the membrane concentration gradients

channel-mediated diffusion

diffusion of solute through a pore

carrier-mediated (facilitated diffusion)

transport of solute by carrier protein down electrochemical gradient

co-transport

co-transport of solutes in the same direction

counter transport

countertransport of solutes in opposite directions

ATP-mediated transport

transport of solute by carrier protein against an electrochemical gradient w ATP hydrolysis providing the driving force

sodium-potassium ATPase pump

ATP-mediated transport


-throughout most parts of the renal tubule


-present on the basolateral side of the tubular epithelial cell


-cell membrane has extensive Na+/K+/ATPase that hydrolyzes ATP and uses the released energy to transport Na+ out of the cell into the interstitium and eventually into the peritubular network


-at the same time K+ is transported from the interstitium to the inside of the cell


3Na+ ions ejected form the cell, simultaneously 2 K+ ions gain entry

fxn of Na-K-ATPase pump:

a) maintains low intracellular sodium


b) creates a net negative charge within the cell


-favours the movement of sodium across the luminal membrane (either via carrier proteins or Na+ cahnnels) into the epithelial cells


-as sodium diffuses down its electrochemical gradient, the energy released is used to co-transport (eg. glucose, aa, Cl-) or counter-transport (eg. H+) other substances

% reabsorbed in proximal tubule

65-70% of filtered load of sodium and water, slightly lower % of filtered chloride reabsorbed by proximal tubule before it reaches loop of henle

proximal tubule

-epithelial cells highly metabolic and have large # mitochondria (to support potent active transport processes)


-extensive brush border (densely packed microvilli to provide an extensive membrane SA)


-amount of Na in tubular fluid decreases along proximal tubule, concentration of Na remains constant b/c water permeability keeps pace w Na reabs


-sodium-hydrogen exchanger (NHE3)


-carbonic anhydrase (CA)


-organic acid secretory systems


-sodium-glucose co-transporter


-

sodium-hydrogen exchanger

located at apical side of luminal membrane of the proximal tubule epithelial cell

carbonic anhydrase

located at apical side of the cell membrane (CAIV) or in the cytosol (CAII) of proximal tubule


-catalyzes the hydration of CO2 and the dehydration of carbonic acid


(H2O + CO2 <-> H2CO3- <-> HCO3- + H+)


-CAIV catalyzes cleavage of carbonic acid into water and CO2 (which diffuses into cytoplasm of proximal epithelial cells)


-intracellular CO2 is rapidly rehydrated to carbonic acid by cytoplasmic CAII


-leads to formation of HCO3- which is then co-transported w Na+ across asolateral membrane of the epithelial cell (Na+/HCO3- co-transporter called NBC1)


-hence, reabs of HCO3- by proximal tubule is dependent on CA activity



organic acid secretory systems

-present at proximal tubule


-secrete variety of substances like uric acid and diuretics into luminal fluid from the blood


-help to deliver diuretics to the luminal side of the tubule where most of them are active




salt transport in proximal tubule is not under hormonal control

sodium-glucose co-transporter (SGLT)

-SGLTs couple glucose w sodium




SGLT-2 (Na:glucose co-transport ratio of 1:1)


-present in the S1 and S2 convoluted section of the proximal tubule


-responsible for the reabs of 90% of glucose filtered in the glomerulus back into the blood stream




SGLT-1 (Na:glucose co-transport ratio of 2:1)


-present in the S3 or straight segment of the proximal tubule


-responsible for reabs of the remaining 10% of filtered glucose

% reabsorbed in loop of henle

20-25% of filtered loads of sodium, chloride, and potassium are reabsorbed in the thick ascending limb of the loop of henle

loop of henle segments

descending thin segment


ascending thin segment


thick ascending segment

loop of henle

-descending limb freely permable to water


-Na+/K+/ATPase pump


-Na/K/2Cl co-transporter (thick ascending loop)

Na/K/2Cl cotransporter (NKCC2)

-in thick ascending loop (which is virtually impermeable to water despite reabs of large amounts of NaCl)

-NKCC2 is an electro neutral co-transporter


-by taking K+ from lumen into the epithelial cell, which also gains K+ from the interstitial fluid (Na+/K+/ATPase pump) there is backflow of K+ into the lumen


-this creates a trans-epithelial voltage along the thick ascending limb that is oriented such that the lumen is positive relative to the interstitial fluid


-this drives the paracellular reabs of luminal divalent cations like Mg2+ and Ca2+




% reabsorbed in distal tubule

4-5% of filtered Na+ in the glomerular filtrate

distal tubule

-first portion forms part of the JG complex (whre distal convoluted tubule comes in contact w the afferent arteriole)


-at this junction, distal tubular cells become highly specialized = macula densa, and respond to changes in Na+


-activation of macula densa triggers highly specialized cells lining the afferent arterioles (granular JGCs) to release renin into blood


-contain Na/Cl co-transporter (NCC)


-ion-specific Ca2+ channels (TRPV5)

TRPV5

ion-specific Ca2+ channels in distal tubule


-mediates reabs of luminal Ca2+ in apical membrane (under control of PTH)


-reabsorbed Ca2+ can then cross the distal tubule basolateral membrane via specific Na+/Ca2+ exchangers and Ca2+/ATPase (that exchanges internal calcium for external H+)

% reabsorbed in collecting duct

reabsorb less than 4-5% of the filterd sodium

collecting duct

last segment


-reabs sodium and water


-secretes potassium


-under control of aldosterone (secreted from the adrenal cotrex -causes reabs of Na+, which can increase blood volume and BP)


-cells have ion channels for Na+ and K+ (no transport systems)


-only one ion (sodium) tat is being abs


-Cl- and HCO3- are left behind, making the lumen negative = driving force that draws K+ out of cells through apical membrane K+ channel, resulting in K+ secretion


-lumen neg potential can also move Cl= back into blood via paracellular pathway


-permeability controlled by ADH

aldosterone role in collecting duct

regulate reabs of Na+ and its coupled secretion of K+


-increases synthesis of proteins including Na+ channel and Na+/K+/ATPase in addition to causing mitochondrial biogenesis

ADH in collecting duct

-secreted from the posterior pituitary


-increases permability of collecting ducts to water thereby concentrating the urine


-stimulates G-protein coupled receptor in the basolateral membrane (V2 recepotrs)


-cAMP produced due to this activation promotes the insertion of pre-formed water channels called aquaporin-2 (AQP2) into the apical membrane