Lecture 6: Sodium Homeostasis (and part of Lecture 7) Flashcards
what hormones regulate extracellular fluid voluem by altering Na excetion by the kidney?
angiotensin II (increase reabsorption) arginine vasopressin (increase reabsorption) aldosterone (increase reabsorption) natriuretic factors (ANP, dopamine, endothelin, ouabain, and ouabain analogues) (increase renal excretion)
describe the reabsorption of Na at different parts of the nephron.
65% proximal tubule
25-30% at loop of henle
3-5% at distal tubule
1-3% at collecting tubule
How does the kidney alter the amount of Na exretion?
changin in the filtered load or
change in graction of filtered Na that is reabsorbed
Describe filtration of Na at the glomerulus
freely filtered
starling forces determine GFR
glomerular capillary flow important determinant of GFR
higher oncotic pressure less filtration
more rapid flow, slower rise in oncotic pressure
Describe reabsorption of Na at the proximal tubule
65% reabsorbed
Na crosses apical membrane via co-transporters (especially with HCO3- in early proximal tubule)
Na absorption is isoosmotic
Na-k-ATPase provides driving force for Na reabsorption
Some Na transport occurs with chloride via paracellular pathway in late proximal tubule
what are the major Na transporters on the apical plasma membrane?
Na/H exchanger
Na/glucose co-transporter
Na/amino acid co-transporter
Na/PO4 co-transporter
How does Na enter the interstitial space?
crosses basolateral membrane via Na/K ATPase and Na/HCO3- costransporter (uses electromotive force despite chemical gradient)
Describe Cl reabsortption at the proximal tubue
facilitated by anion exchangers: Cl/HCO3- exchanger, Cl/formate, Cl/oxalate
Describe the paracellular pathway of Na transport
in late proximal tubue, Cl- concentration in tubular lumen is greater than in interstitial space, Cl- moves across tight junctions creating a lumen positive potention that drives Na through the tigh junctions
What happens to Na in the interestitial space?
enters peritubular capillaries (rate limiting of Na reabsorption)
leaks back across tight junctions into the tubular lumen
How is Na reabsorption affected by oncotic and hydrostatic pressure of the peritubular capillary?
increasing oncotic pressure or decreasing hydrostatis pressure in peritubular capillary will increase Na reabsorption
Describe reabsorption of Na in the loop of henle
25-35% reabsorption of filtered Na occurs here
50% of the reabsorbed Na travels thru the transccellular pathway and 50% through the paracellular patway
Na crosses apical via Na,K,2Cl co-transporter
loop diuretics block Na reabsorption in the segment by blocking Na.K,2Cl transporter
Paracellular transport of Ca2+ and Mg2+ occur here
no active transport across descending limb and thin ascending limb
some passive transport in the thin ascending limb
active transport across the thick ascending limb**
Crosses basolateral via the Na-K-ATPase and enters interstitial space
Describe the paracellular pathway in the loop of henle
depends on developing positive charge in tubule as K is recycled across apical plasma membrane via ROMK
this drives Na, Mg2+ and Ca2+ uptake
describe reabsorption in the distal nephron
4-8% of filtered Na reabsorbed
early distal convoluted tubule reabsorbs Na via the Na,Cl co-transporter (activated by aldosterone, inhibited by thiazide diuretics)
late distal convoluted tubule uses ENaC (activated by aldosterone and arginine vasopressin and inhibited by K sparing diuretics [amiloride, triamterene], trimethoprim, and spironolactone)
Na crosses basolateral membrane via Na-K-ATPase to enter interstitial space
What is absorbed in the early distal convoluted tubule?
Na+, Ca++, Mg++
Ca++ and Mg++ reabsorbed transcellularly
when Na,Cl co transporter inhibited, reabsorption of filtered Ca++ and Mg++ is inreased due to enhanced proximal tubular reabsorption
Describe conversion of angiotensinogen to angiotensin II
renin (excreted by JG cells) cleaves angiotensinogen to angiotensin I
ACE cleaves angiotensin I to angiotensin II
what does angiotensin II do?
constricts efferent arteriole
reduces renal plasma flow and glomerular palsma flow
increases glomerular hydrostatic pressure
increase filtration fraction while maintaining GFR
increase peritubular oncotic pressure + decrease peritubular hydrostatic pressure –> increase Na and H2O reabsorption in proximal tubule
increases systemic BP (arterial vasoconstriction, increasing proximal tubular Na reabsorption, release aldosterone increasing distal tubular Na reabsorption)
filtration fraction equation
FF = GFR/RPF
What regulates renin release?
amount of solute delived to macula densa
stretch of the afferent arteriole
sympathetic nervous system
prostaglandins
how does angiotensin II effect gfr?
selective efferent arteriolar constriction –> increases GFR by increasing hydrostatic pressure
however there is a decrease in renal plasma flow leading to rise in oncotic pressure –> reduce GFR
net result = little change in GFR
Describe arginine vasopressin
it is secreted in response to osmotic stimuli or non-osmotic stimuli like volume deption or reduced effective arteriolar volume
activates Na,K,2Cl cotransporter in thick ascending limb –> increasing Na transport across cells
activats NCC and ENaC in distal nephron
Describe aldosterone
secreted in response to angiotensin II and increased plasma K
increases Na reabsorption by activating Na-Cl cotransporter, ENaC and increasing basolateral NaKATPase in distal nephron
increases K and H secretion in distal nephron
Secretion of aldosterone from adrenal cortex is a response to what?
ang II
increased plasma [K]
how does aldosterone affect ENaC?
effects levels of ENac mRNA in kidney (alpha subunit expression increased)
regulates ENaC post-translational mechanisms
Describe ANP
secreted by atrial myocytes in response to stretch
increases GFR and inhibits NA reabsorption in inner medullary collecting tubule due to inhibition of the Na/K-ATPase –> increasing urinary Na excretion
Describe ouabain analogues
inhibits NaKATPAse –> increase renal Na excretion
secreted by hypothalamus
Describe dopamines effect on Na excretion
increases urinary Na excretion due to inhibition of Na/H exchanger and Na/K ATPase in proximal tubule
inhibits Na reabsorption in more distal nephron sements
Describe endothelin’s effect on Na excretion
increases urinary Na excretion by inhibiting ENaC
Describe PGs effect on Na reabsorption
prostacyclin and PGE2 enhance renin secretion by JG apparatus
specific PGs affect glomerular hemodynamics by dilating the afferent and efferent arterioles
renal Pgs (PGE2) promote urinary Na excretion by inhibiting Na reabsorption in the thick ascending limb and cortical collecting duct
Describe the effect of the activation of the sympathetic nervous system on Na reabsorption
enhances renin secretion leading to increase in Ang II and aldosterone
enhances Na reabsorption (proximal tubule)
Describe Gitelman’s Syndrome
loss of function mutation from the Na,Cl co transporter in early distal tubule resembles treatment with a thiazide diuretic clinically presents with low-normal ECF volume low-normal BP elevated renin and aldosterone low K+ hypocaciuria
Describe pseudohypoaldosteronism Type I
loss of function mutation of ENaC or mineralocorticoid receptors –> making collecting tubule unable to respond to aldosterone
AR disorder
characterised by:
volume depletion, hypotension
hyperkalemia despite elevated plasma aldosterone
What are some common causes of volume overload?
advanced renal failure
heart failure
liver failure
nephrotic syndrome
How does an increase in Na and H2O in the IT space manifest?
edema
lung –> dyspnea
extremities –> swelling
abdomen –> ascites
how does an increase in Na and H2O in the IV space manifest?
hypertension
what are two factors that drive the formation of edema?
renal retention of Na and water?
change in capillary starling forces (net movement of fluid out of capillary bed and into interstitial space)
what are some characteristics of ESRD?
volume overload, retention of Na and H2O and increased hydrostatic pressure
what disorders will you see an expansion of the extracellular fluid volume and underfilling of the arterial bed: “decreased effective arterial volume”
CHF, cirrhosis, some nephrotic syndromes
describe volume overload in heart failure
decreased CO –> decreased pressure at baroreceptors and decreased flow to kidneys –> RAAS activation –> renal retention of Na and water
