L10 Modulation of urinary concentration, osmolytes, diuretics, and potassium homeostasis Flashcards
inulin clearance
- only filtered (not absorbed or secreted)
→ good GFR indicator - independent of plasma concentrations since it is just filtered
- passive process
creatinine clearance
- almost only filtered - secreted slightly at low GFR (not often)
→ good endogenous marker of GFR - independent of plasma concentrations since mostly just filtered
glucose clearance
- fully reabsorbed
→ over normal range of solute, clearance is 0 - glucose in urine is pathological (> threshold)
PAH clearance
- secreted
- BUT very high plasma PAH levels → saturate secretory process in proximal tubule → less efficient at clearing plasma of PAH
clearance of ___ and ___ approaches the clearance of inulin at ___ plasma concentrations
clearance of glucose and PAH approaches the clearance of inulin at high plasma concentrations
- organic osmolytes / compatible solutes purpose?
→ increase of overall osmolyte concentration from ___ to ___ ___ - betaine: what is it?
- sorbitol: what is it? elevated mainly in ___
- inositol: elevated mainly in ___
- organic osmolytes / compatible solutes: small molecules that allow cells to maintain their internal water balance when exposed to hypertonic surround without compromising cellular function
→ increase of overall osmolyte concentration from cortex to inner medulla - betaine: amino acid
- sorbitol: sugar alcohol (like glucose), elevated mainly in inner medulla
- inositol: elevated mainly in outer medulla
GPC = glycerophosphocholine (GPC)
accumulated in cells exposed to ___ solutions - in ___ ___ ___:
- ↑ [NaCl] → ↑ accumulation of ______
- ↑ [raffinose] → ↑ in ______
- ↑ [urea] → ↑ in ______ to protect against denaturing effect of urea
- GPC = ___ and ___
GPC = glycerophosphocholine (GPC)
accumulated in cells exposed to hypertonic solutions - in cultured renal cells:
- ↑ [NaCl] → ↑ accumulation of sorbitol, inositol, betaine, and GPC
- ↑ [raffinose] → ↑ in sorbitol, inositol, and betaine, NO increase in GPC
- ↑ [urea] → ↑ in GPC only to protect against denaturing effect of urea
- GPC = compatible and counteracting
accumulation and release of osmolytes during anti-diuresis
- sorbitol: synthesized from ___ by ___ ___. ↑ ___ → ↑ ______ + ______
- [inositol] ↑ by ______ (related to ___)
- betaine + taurine: elevated by uptake via ______
- ↑ [NaCl] or [urea] → ___ gets converted to ___ via ___
- ↑ GPC levels by inhibiting its degradation by ___
accumulation and release of osmolytes during anti-diuresis
- sorbitol: synthesized from glucose by aldose reductase. ↑ osmolality → ↑ transcription of aldose reductase + osmolyte transporter gene
- [inositol] ↑ by Na/inositol cotransporters (related to SGLT2)
- betaine + taurine: elevated by uptake via separate Na, Cl, osmolyte cotransporters
- ↑ [NaCl] or [urea] → choline gets converted to GPC via phospholipase
- ↑ GPC levels by inhibiting its degradation by phosphodiesterase
excretion of fluid during diuresis
(ECF becomes more ___)
- osmolytes rapidly ___ from cell when osmotic pressure ___, likely through ______ channels
excretion of fluid during diuresis
(ECF becomes more hypotonic)
- osmolytes rapidly released from cell when osmotic pressure falls, likely through swelling-activated anion channels
common diuretics
proximal tubule: ___ diuretics
- ___
- ___ at high levels (in ___)
- ___: ___ ___ inhibitor, reduces ___ reabsorption by preventing ___ reabsorption
TAL: ___ diuretics
- ___ + ___: ___ inhibitors
early distal tubule: thiazide diuretics
- ___: ___ inhibitor
late distal tubule/ CCD: ___ ___ diuretics
- ___ + ___ - ___ blockers
- inhibit secretion of ___ by inhibiting reabsorption of ___ (no driving force is established for ___ to leave into lumen)
common diuretics
proximal tubule: osmotic diuretics
- mannitol
- glucose at high levels (in diabetes mellitus)
- acetazolamide: carbonic anhydrase inhibitor, reduces bicarbonate reabsorption by preventing water reabsorption
TAL: loop diuretics
- bumetanide + furosemide: NKCC2 inhibitors
early distal tubule: thiazide diuretics
- hydrochlorothiazide: NCC inhibitor
late distal tubule/ CCD: potassium sparing diuretics
- amiloride + triamterene - ENaC blockers
- inhibit secretion of potassium by inhibiting reabsorption of sodium (no driving force is established for potassium to leave into lumen)
- potassium homeostasis. where does potassium in diet go?
- overall balance of potassium determined by ___
- ___ and ___ stimulate K secretion
- ______ matches amount absorbed from intestine
- potassium in diet → some excreted in feces, but most reabsorbed by intestine
→ then most stored in tissues, sequestered in cells - overall balance of potassium determined by [𝐾]𝑝𝑙𝑎𝑠𝑚𝑎
- ADH and aldosterone stimulate K secretion
- secretion in urine matches amount absorbed from intestine
K⁺ distribution
- ___ pool»_space;> ___ pool → must be tightly regulated
- all cells have ______ to bring K⁺ into cells
- recycling of potassium determines membrane potential → sets state of excitability for muscle + nerve cells
- higher K⁺ → ______
- lower K⁺ → ______
K⁺ distribution
- intracellular pool»_space;> extracellular pool → must be tightly regulated
- all cells have Na⁺/K⁺ ATPase to bring K⁺ into cells
- recycling of potassium determines membrane potential → sets state of excitability for muscle + nerve cells
- higher K⁺ → easier to fire AP
- lower K⁺ → cell hyperpolarized → less excitable
factors that influence plasma potassium levels? (8)
factors that influence plasma potassium levels
- insulin
- epinephrine
- aldosterone
- acid-base status: during acidemia , protons go into cells, potassium goes out → hyperkalemia (only strong acids, lactic acid doesn’t have same effect on cells)
- ECF osmolar status: cells put in hypertonic solution will lose solute to inflate (one of these being potassium)
- exercise: small amount of potassium release when muscles contract → elevate plasma [K⁺]
- cell lysis: since extracellular K⁺ is so high, small amount of cell lysis can lead to increase potassium levels
- K⁺ gain/loss from body
K⁺ absorption / secretion characteristics and mechanisms in proximal tubule, TAL, late distal tubule / CCD and on basolateral side?
K⁺ gets filtered, then reabsorbed mostly by proximal tubule, then secreted in distal tubule according to need
apical side:
proximal tubule
- reabsorbed paracellularly through tight junctions
- driven by lumen positive voltage that occurs in superficial nephrons (outer part of cortex)
TAL
- NCCK2 (K⁺ goes in) + recycling occurs via ROMK2 (K⁺ goes out)
- so direction of potassium depends on relative conductances between apical and basolateral membranes
- lumen voltage even more positive → also paracellular K⁺ reabsorption
late distal tubule / CCD:
- principal cells: Na⁺ enters via ENaC, potassium secreted in response to voltage change by RIMK1 + ROMK3 → major site of K⁺ secretion
- intercalated cells: absorb K⁺ in exchange for H⁺
basolateral side:
- Na⁺/K⁺ pumps
- potassium can be recycled @ basolateral membrane without being secreted
ROMK (Renal Outer Medullary K⁺) channel
- ___ transmembrane segments, form ___
- allow for ______ in the principal cells of the collecting duct (___ + ___)
- in TAL, ___ allows for ______
- BK channels are responsive to ___ ___ in the lumen
ROMK (Renal Outer Medullary K⁺) channel
- 2 transmembrane segments, form tetramer
- allow for K⁺ secretion in the principal cells of the collecting duct (ROMK1 + ROMK3)
- in TAL, ROMK2 allows for recycling of potassium
- BK channels are responsive to flow rate in the lumen
factors influencing urinary K⁺ excretion? (6)
- increase in plasma uptake stimulates ___ secretion → acts on ___ ___ to stimulate ______ (___ ___ proteins) → ↑ ___ pumps on ___ membrane + ↑ ___ ___ channels
factors influencing urinary K⁺ excretion
- dietary intake of K+
- mineralocorticoids (aldosterone)
- urinary Na⁺ excretion (Na⁺ entry into collecting duct increases secretion of K⁺)
- urinary flow rate (if flow rate is high, K⁺ doesn’t get a chance to build up → efficient secretion)
- H⁺ balance (H⁺ can inhibit K⁺ channels)
- diuretic drugs
- increase in plasma uptake stimulates aldosterone secretion → acts on collecting duct to stimulate transcription of AIP genes (aldosterone induced proteins):
- ↑ Na⁺/K⁺ pumps on basolateral membrane
- ↑ apical K⁺ channels
how can black licorice lead to heart arrhythmias?
- 11 β-HSD 2 makes mineralocorticoid receptor more selective by converting cortisol to cortisone so aldosterone can exert proper effects to upregulate sodium pumps
- glycyrrhizin is inhibitor of 11 β-HSD 2 → hyperstimulation MR receptors → increased Na⁺ reabsorption and K⁺ secretion
- too low K⁺ → cardiac arrhythmias
