Potassium, Calcium and H+ Homeostasis Flashcards
Where is most potassium located
98% is IC
Changes in EC K cna impact resting potential…more K—decreased RM potential—-increased exciatbility
over 5.5 - hyper
under 3.5 - hypo
Dietary K+ changes
Ingestion of small amounts of GI COULD have significant effects if retained in the ECF
Dietary changes prevented by - Rapid cellular uptake of K (epinephrine, insulin, aldosterone…increase Na-K-ATPase)
AND slower renal excretion
Renal tubular transport of K+
2/3 reabsorbed in PT, and 25% in TALH…occurs independent of postassium status
ONly 10% delivered to distal neprhon BUT higher FL percentages excreted in the urine because K+ secreted int he late distal and collecting tubule
Physiologic regulation of excretion primarily achieved by controlling rate of K+ secretion
K+ secretion mechanism
Uptake across basolateral iva Na-K-ATPase
Efflux across lumanial via K channels and K-Cl cotransporters
Na reabsorption through luminal channel creates lumen negative potential which also promotes K+ secretion
In K+ reapsorption in the distal and collectint tutuble
Low capacity K+ reabsorption will reduce K_ excretion
Uptake across luminal membrane via energy dependnet K-H anti-porter
Efflux across basolateral membrane via K+ selective channels
Physiologic changes to EC fluid K+ homeostasis
Hypertonicity - hypertonic ECF causes cells to shrink and increases intracellular K+ concentration…this increase K+ efflux and therefore hyperkalemia
Cell lysis - realse K_ into ECF…local hyperkalemia…exercise-induced muscle
breakdwon
Changes in H+ cause paralelll changes in ECF (metabolic alkalosis is decreased H and K)
Metabolic acidosis due to inroganic acids increasse plasma K+ to a much greater extent than simlr by orgnaic
Resp acid-base disorders have little or no effect on plasma K+
Regulation of tubular postassium secretion
Increase in ECF concentration increase K+ secretion and thus increase in K+ urine excretion by
Direct increase in ATPase activity on distal neprhon cells and
Direct increase in aldosterone secretion (increase in ATPase activity and increased luminal membrane K+ permability)
Effect of tubular fluid flow
Increased flow - increased K+ secretion
Increased flow minimizes the rise in tubular fluid K concentration
increased flow increases Na reabsorption—-increased ATPase activity—-increased intracellular K+
Loop Diuretics effect
Decreases K+ reabsorption in the thick limp
Increased distal secretion due to increased distal tubular fluid flow and increased distal na reabsorption…inrease N-K-ATPase—increase intracellular K
Can lead to hypokalemia
Integrated response to hypocalcemia
Maintenance of normal plasma Ca dependent on PTH mediated effects
Normally a drop in caclium leads to increase in PTH…this increase renal calcium reabsorptio nand decreases excretion
How much calcium is free?
45% is free
50% is protein bound
ONly the free portion is filtered
Renal calcium reabsorption
From proximal tubule and TALH…PARACELLULAR
Most in the PT
Familial hypomagnesemic hypercalciuria - mutation in claidun 16 - protein compoennt of TAL tight juncton
Ca reabsorptioin in the distal tubule
Channel mediated
Reabsorbs Ca via lumnal TRPV5 channel….binds to 28K…removed through PMCA1b (ATP depdnent) or NCX1 (Na/Ca antiporter)
Reabsorbes Mg via luminal TRPM6 channel (Binds to MgBP?)…leaves same way as Mg
PTH and Ca reabsoortiojn
PTH increases Ca reabsorption in the distal tubule due to stimulation of Ca ATPase and Na-Ca exchangs on basolateral membrane
GI tract response to hypocalcemia
Renal contribution is that high PTH stimulates 1 alpha hydroxylase in proximal tubules which activates vit D which allows more GI rabsorption
Bone response to hypocalcemia
When you resorb the bone, free up phosphate which can lead to hyperphosphatemia
Prevented by inhibitory effect of PTH on renal HPO4 reabsorption
PTH and PO4 reaborption mech
INcreased PTH decrease HPO4 reabsorptiin in the proximal tubule due to inhibition of
Na-HPO4 co transport on the luminal membrane
H+ production
VOlatile acid via oxidative metabolism…this is eliminated by the lungs
Fixed acid - by amino acid metabolism…increases with exercise and diabetes
lines of defense to prevent acid-induced acidification of body fluids
Physicochemical buffering Respiraotry compensation (CO2 eliminaion) Renal compensation (H+ excretion and generation of HCO3-)
Physicochemical buffering
A buffer - molecule that combines with or releases H+ ions
Buffer systems - minimize the change in free H+ concentration
Capacity depends on concentration of the buffer pair
pH at which buffer ocmponent concentrations equal is the pK…this is the point of greatest buffering capacity***
Combined effects of all buffers in a given compartment determines the free H+ concentration (isohydric principle)
Bicarb buffer system
Lungs regulate the CO2 levels and kidnneys regulate plasma
Carbonic anhydrase is responsible for conversion…this converts all of the H2CO3 to water and CO2
Multiply .03 by pCO2 to mmol/L dissolved CO2
Ratio of base/acid determine the pH…20/1 is ideal
The base here is HCO3 and the acid is CO2
pH=pKa +log(HCO3/CO2)
Resp system effect
CO2 diffuse from tissue to RBC…converted to H+ and HCO3
H+ buffered by de-oxygenated hemoglobin
HCO3 diffuse out of RBC in exhcnage of CL- (chrloide shift)
Process reversed at lungs
Alveolar ventilation regulated
Control arterial pCO2
Regulated by H+ and pCO2
Response to infused acid load
1 - physochemical buffering…after buffering plasma HCO3 reduced and totoal CO2 is increased…pH is decreased
2 - Respiration eliminates the CO2 generated in the buffering process…this increases the pH
3 - continued low pH will stimulate respiration and further decrease pCO2
4 - renal compensation…pH returend to close to normla value but the plasma HCO3 is depleted and excess H+ retained in combo with other buffers
Kidneys will generate new HCO3 to restore ECH concentration and excrete the excess H+
How do kidneys reabsorb bicarb?
More than 99% reabsrbed
Indirect
Intracellular generation of H+ and HCO3
H+ secreted into lumen…combines with filtered HCO3 to from CO2 and H@O
Intracellular \ly generated HCO3 transported across BL membrane to ECF
For every 1 mEq of gfiltered HCO3 converted, i mEq added to ECF
Regulation of biacrb reabsorption
Arterial blood CO2…more CO2…more H secretion…more HCO3 reabsorption
Na reabsorption…increase Na reabsorption…intease Na-H antiport…increase H secretion….increased HCO3 reabsorption
Renal generation of new bicarbonate
Occurs primarily in the distal nephron…intercalated (vs principal) collecting tubule cells
Generation of new depends on availability of urinary buffer to accept secreted H+ like titratable acid
Availability of HPO4 and H2PO4 as tubular buffer is limited because filtered load is low
HCO3 can be generated from glutamien metabolism in the proximal tubule…also generates ammonium ion secreted into the tubular lumen
The NH4 is reabsorbed in the TALH…subs for K
Interstitial NH4 exsits in equlibirium with NH3…NH4 transported across intercalated cells into lumen and excreted…NH3 transported into lumen…interacts with secreted H+ resulting in new HCO3 syntehssi
Regulation of HCO3 syntehsis
Metabolic acidosis increases glutamine metabolism and thus HCO3 synthesis and NH3 availability
HCO3 synthesis also regulated by aldosterone…increase in aldosterone—-increased H+ ATPase—-increased H++ secretion—-increase HCO3 reabsorption and syntehsis
Resp and met disturbances
Resp acidosis - increased pCO2 with decreased pH…opposited fro alk…caused by change in pCO2
met - shift in pH from primary change in plasma HCO3
Acidosis - Increase H+ leads to decreased HCO3…diabetes
Alkalosis - decreased H+ leads to more HCO3-…chronic vomiting
Stimulus for new HCO3 syntehsis in resp distrubances
High pCO2 stimulates H+ secretion
What stimulates respiration
Reduced pH will stimulate respiration and therefore decrease pCO2
Requirement and mechanism
Resotre plasma HCO3 to normal
To this by reabsorbing all filtered HCO3 and generate new HCO3
PRoblem with this is that low pCO2 preidcts low secretion of H+ but low plasam HCO3 results in greatly recued filtered load of HCO3…thus still sufficient H+ to reabsorb all filtered HCO3 and generate new HCO3
Anion gap
Na - (Cl+HCO3)
With diabetic ketoacidosis…decreased HCO3 and increase anion gap
HCl induced acidosis…decreased HCO3 but anion gap norma because CL will increased as HCl buffered
In diarrhea…decreated Cl/HCO3 exhcnage in GI tract—-decreased HCO3 but anion gap normal (decreased exchanger —-loss of HCO3 in stool but retention of plasam Cl)
