Potassium, Calcium and H+ Homeostasis

Question 1

Where is most potassium located

Answer 1

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

Question 2

Dietary K+ changes

Answer 2

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

Question 3

Renal tubular transport of K+

Answer 3

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

Question 4

K+ secretion mechanism

Answer 4

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

Question 5

In K+ reapsorption in the distal and collectint tutuble

Answer 5

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

Question 6

Physiologic changes to EC fluid K+ homeostasis

Answer 6

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+

Question 7

Regulation of tubular postassium secretion

Answer 7

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)

Question 8

Effect of tubular fluid flow

Answer 8

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+

Question 9

Loop Diuretics effect

Answer 9

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

Question 10

Integrated response to hypocalcemia

Answer 10

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

Question 11

How much calcium is free?

Answer 11

45% is free
50% is protein bound

ONly the free portion is filtered

Question 12

Renal calcium reabsorption

Answer 12

From proximal tubule and TALH…PARACELLULAR

Most in the PT

Familial hypomagnesemic hypercalciuria - mutation in claidun 16 - protein compoennt of TAL tight juncton

Question 13

Ca reabsorptioin in the distal tubule

Answer 13

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

Question 14

PTH and Ca reabsoortiojn

Answer 14

PTH increases Ca reabsorption in the distal tubule due to stimulation of Ca ATPase and Na-Ca exchangs on basolateral membrane

Question 15

GI tract response to hypocalcemia

Answer 15

Renal contribution is that high PTH stimulates 1 alpha hydroxylase in proximal tubules which activates vit D which allows more GI rabsorption

Question 16

Bone response to hypocalcemia

Answer 16

When you resorb the bone, free up phosphate which can lead to hyperphosphatemia

Prevented by inhibitory effect of PTH on renal HPO4 reabsorption

Question 17

PTH and PO4 reaborption mech

Answer 17

INcreased PTH decrease HPO4 reabsorptiin in the proximal tubule due to inhibition of
Na-HPO4 co transport on the luminal membrane

Question 18

H+ production

Answer 18

VOlatile acid via oxidative metabolism…this is eliminated by the lungs

Fixed acid - by amino acid metabolism…increases with exercise and diabetes

Question 19

lines of defense to prevent acid-induced acidification of body fluids

Answer 19

Physicochemical buffering
Respiraotry compensation (CO2 eliminaion)
Renal compensation (H+ excretion and generation of HCO3-)

Question 20

Physicochemical buffering

Answer 20

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)

Question 21

Bicarb buffer system

Answer 21

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)

Question 22

Resp system effect

Answer 22

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

Question 23

Alveolar ventilation regulated

Answer 23

Control arterial pCO2

Regulated by H+ and pCO2

Question 24

Response to infused acid load

Answer 24

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+

Question 25

How do kidneys reabsorb bicarb?

Answer 25

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

Question 26

Regulation of biacrb reabsorption

Answer 26

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

Question 27

Renal generation of new bicarbonate

Answer 27

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

Question 28

Regulation of HCO3 syntehsis

Answer 28

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

Question 29

Resp and met disturbances

Answer 29

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

Question 30

Stimulus for new HCO3 syntehsis in resp distrubances

Answer 30

High pCO2 stimulates H+ secretion

Question 31

What stimulates respiration

Answer 31

Reduced pH will stimulate respiration and therefore decrease pCO2

Question 32

Requirement and mechanism

Answer 32

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

Question 33

Anion gap

Answer 33

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)