Lec 45 Distal Tubule, Collecting Duct, ADH, RAAS, Erythropoietin, ANP Flashcards
What is the physiologic role of distal tubule and collecting duct?
- fine tune what we excrete and what we keep
- acidify urine
What are mechs of Na and Cl transport in early distal tubule?
apical:
- Na/Cl cotransporter [1 Na in, 1 Cl in]
basolateral:
- Na/K ATPase [3 Na out, 2 K in]
- Cl channel out
Is early distal tubule diluting or concentrating?
diluting – continues to create free water
Is early distal tubule permeable to water?
no – impermeable
What are the two cell types of late distal tubule and collecting duct?
principal cells
intercalated cells
What do principal cells do?
- reabsorb Na
- secrete K
- respond to ADH/aldosterone
What do alpha intercalated cells do?
- secrete H
- reabsorb K
What do beta intercalated cells do?
- secrete HCO3
What is mech of principal cells?
apical: - Na in via Na channel [driven by gradient] - K secreted to lumen via K channel basolateral: - Na/K ATPase [3 Na out, 2 K into cell] - negative
Is lumen positive or negative voltage in late distal tubule and collecting duct? What does this mean?
- negative voltage
- means you get paracellular Cl diffusion out of lumen
How is Cl transported in late distal tubule and collecting duct?
- via paracellular diffusion it is reabsorbed
- negative potential of lumen is driving force
How is K transported in late distal tubule and collecting duct?
- via K channel secreted in principal
- via H-K ATPase reabsorbed in alpha intercalated
What is mech of alpha intercalated cell?
apical:
- H-ATPase transfers H out of cell into lumen
- H-K ATPase: [1 H into lumen, 1 K into cell]
basolateral:
- Na-K ATPase [3 Na out of cell into capillary, 2 K into cell]
- K channel out to capillary
- HCO3-Cl antiporter [HCO3 out of cell into capillary, Cl into cell]
- Cl channel out
What primarily drives K transport?
H-K ATPase
What happens to principal cell action when you have lots of K?
- more principal cell action since principal cells are excreting K
Do principal cells or intercalated cells play bigger role in K regulation?
principal cells
What is the mech of HCO3 transport in alpha intercalated
- HCO3 generated with H from CO2 and H2O in alpha intercalated
- H used for the H-K ATPase that drives K transport
- HCO3 reabsorbed using HCO3/Cl antiporter
What are the 3 paradigms of acid-base regulation by alpha intercalated cells?
- reabsorbing HCO3
- excreting H as titratable acid
- excreting H as NH4
What is mech of H+ secretion by alpha intercalated cell? Is there a difference between this mech for secretion via titratable acid or NH4?
- in cell: CO2 and H2O –> H2CO3 –> H + HCO3 via carbonic anhydrase
- on apical side of cell: H-ATPase and H-K exchanger get rid of H into lumen
- on basolateral side HCO3 reabsorbed via HCO3-Cl exchanger
- no difference in mech for titratable acid vs NH4
What is mech of H excretion as a titratable acid in alpha intercalated? What is feedback?
- some acid HA dissociated into H and A in lumen
- extra H associates with HPO4 and SO4 –> H2PO4, HSO4
- excreted as acid
- extra H feeds back and inhibits H-ATPase and H-K ATPase so you don’t get too acidic
What is mech of H excretion via NH4+ in alpha intercalated? Why is this a preferable method of excretion?
- NH3 in lumen + H –> NH4+
- NH3 comes from proximal tubule glutaminase rxn
- good method of excretion because it doesn’t dissociate in urine so can excrete acid without lowering pH more
What is mech of bicarbonate reabsorption in alpha intercalated?
- H ion secreted and binds filtered HCO3 –> H2CO3 –> H2O + CO2 allows HCO3 reabsorption and H recycled
- if not sufficient HCO3 in lumen, H excreted because there is no other way to reabsorb it
What are 3 ways of getting more HCO3 from alpha intercalated?
- NH4 and titratable acid mech form new HCO3 that is reabsorbed
- HCO3 recycling mech causes reabsorption of another HCO3
What happens to principal cell mech if you are alkylotic?
- you have lots of HCO3 filtered and little H secreted
- you can’t reabsorb all the HCO3
What happens to principal cell mech if you are acidotic?
- you secrete more H than HCO3 is filtered
- first you will reabsorb all the HCO3 you can
- then you will still have leftover H and you will need to secrete it
What is long term change in kidney when you are acidotic?
- upregulate glutaminase so get more NH3 creation in prox tubule
What is ADH?
hormone that regulates blood volume and BP by regulating tubular transport, free water creation, and reabsorption of free water
also vasoconstricts periphery
Where is ADH generated?
- in hypothalamus precursor synthesized and then converted to ADH and secreted by posterior pituitary
what do osmoreceptors do?
- sense change in osmolarity of plasma
- at increased osmolarity –> induce ADH release
What do baroreceptors do?
- sense change in BP
- if BP decreases by 10-20% get massive change in ADH
- causes tubular effects and vasoconstriction
What 4 things induce ADH receptors?
- increased osmolarity via osmoreceptors
- decreased BP via baroreceptors
- angiotensin II
- pain
- nicotine
What are three non-receptor things that increase ADH release?
- angiotensin II
- pain
- nicotine
What are two non-receptor things that decrease ADH release?
- ANP
- ethanol
What does angiotensin II do to ADH release?
increase ADH
What does pain do to ADH release?
increase ADH
What does nicotine do to ADH release?
increase ADH
What does ANP do to ADH release?
decrease ADH
What does ethanol do to ADH release?
decrease ADH
What two ADH receptors and what types of receptors are they?
Vascular V1 receptor
- Gq couple –> phospholipase C –> DAG/IP3 –> increase Ca
Tubular V2 receptor - on principal cells in distal tubule and collecting duct
- Gs couple –> adenylyl cyclase –> cAMP
What happens to urine conc with no ADH?
- low activity of Na/Cl/K transport
- no urea coming out of collecting duct
- low/moderate longitudinal gradient
- no permeability of late distal tubule and collecting duct to H2O
- excrete hypotonic urine
What happens to urine conc with ADH?
- more hypertonic urine
What is mech of ADH increasing H2O permeability in collecting duct?
- bind V2 receptor
- phosphorylate storage vesicle containing aquaporins
- causes aquaporin-2 to insert in apical membrane
Overview of RAAS system?
- liver makes angiotensinogen
- renin from kidney converts angiotenisnogen to angiotensin I
- ACE from lung converts angiotensin I to angiotensin II
What is rate limiting step of RAAS system?
renin converting angiotensinogen to angiotensin I
Where is renin produced
juxtaglomerular cell in kidney afferent arteriole
What are the 4 main things that control renin release?
- renal vascular baroreceptor
- macula densa mechanism
- renal sympathetic nerves
- Angiotensin II
What is the macula densa mech of renin release?
decreased arterial pressure
- -> decreased Pgc
- -> decreased GFR
- -> decreased delivery of NaCl to macula densa cells in distal convoluted tubule
- -> macula densa signal to increase renin secretion and decrease afferent resistance [via TG-feedback]
- -> increased renin causes increase angiotensin II
- -> increased angiotensin II causes increased BP
How does angiotensin II control renin release?
angiotensin II does feedback inhibition of renin
How do renal sympathetic nerves control renin release?
- sympathetic nerve fibers innervate juxtaglomerular cells and cause them to release renin
How do renal vascular baroreceptors control renin release?
- afferent arteriole senses low pressure
- causes juxtaglomerular cells to release renin
How do prostaglandins control renin release?
stimulate renin release
How does K control renin release?
stimulates renin release
How does ADH control renin release?
stimulates renin release
How does ANP control renin release?
inhibits renin release
What are mech of angiotensin II?
- increase sympathetic activity
- increase proximal Na/Cl reabsorption, H2O retention
- increase K excretion
- stimulate adrenal cortex release of aldosterone which has direct effect on principal cells [more K excretion]
- vasoconstrict to increase BP
- stimulate posterior pituitary to secrete ADH [which then increases collecting duct H2O absorption]
What does erythropoietin do?
kidney releases erythropoietin and causes production of RBCs
What happens to erythropoietin in people on dialysis?
- people on dialysis can’t make their own erythropoietin
What stimulates erythropoietin?
- hypoxia due to decreased RBC count
- decreased Hb
- decreased availability of O2
Where is ANP released? what stimulates release?
- synthesized in atrial myocytes
- release stimulated by pressure changes in heart [high P, big volume]
What does ANP inhibit?
ADH
angiotensin II
What are 4 main actions of ANP?
- stimulate Na and H2O loss at kidney
- inhibit antagonist hormones [ADH/angiotensin]
- suppress thirst
- dilate blood vessels
What does ANP do to renal vasculature tone? RBF? GFR? Kf? medullary blood flow?
- causes vasodilation afferent arteriole
- increases RBF
- increases GFR
- increases Kf [by relaxing mesangial cells]
- increases bloodflow through vasa rect so washes out some of longitudinal gradient so you excrete more Na/H2O
