BERNE AND LEVY (5TH ED.

) POTASSIUM, CALCIUM, PHOSPHATE

CHAPTER 37 HOMEOSTASIS

POTASSIUM HOMEOSTASIS Pathophysiological: Displace plasma [K+] from normal
Total body K+ = 50 mEq/kg body weight; Acid-Base Balance
= 3,500 mEq/70kg individual Metabolic acidosis increases plasma [K+]
98% K+ in ICF; 150 mEq/L o Inorganic (HCl, H SO ) > Organic (lactic, acetic, ketoacids)
2 4

2% K+ in ECF; 4 mEq/L Organic anions may enter cell

ECF vs ICF concentration difference is due to with H+ eliminates need for
Na/K-ATPase K+/H+-exchange
o Hyperkalemia [K+] > 5.0 mEq/L Organic anions may stimulate
Tall, thin T waves insulin secretion moves K+
Prolonged PR interval
Depressed ST segment into the cells
Lengthened QRS interval Metabolic alkalosis decreases plasma [K+]
As plasma [K+] 10 mEq/L o As H+ moves across, K+ moves in opposite
P wave disappears
QRS interval broadens Respiratory disorders little or no effect
ECG looks as sine wave
Ventricles fibrillate Plasma Osmolality
o Hypokalemia [K+] < 3.5 mEq/L ECF osmolality K+ release, ECF [K+]
ECF osmolality ECF [K+]
After a meal, the rise in plasma [K+] is prevented Associated with changes in cell volume
thru rapid uptake of K+ into cells o As water moves across, the [K+] driving
o Excretion of K+ in kidneys is relatively force changes
slow @6 hours
To maintain the total body K+ constant, all the K+ Cell Lysis causes K+ release hyperkalemia
absorbed by the GIT must be secreted by the
kidneys Exercise causes K+ release
Regulated by two mechanisms:
o Regulatory mechanisms in the ECF Drugs that induce hyperkalemia
o Renal adjusting mechanisms keeping the
Risk is increased in patients with:
amount of K+ in the body constant vs
o Diabetes Mellitus,
dietary K+ intake
o Renal Insufficiency, and

o Elderly
FACTORS AFFECTING DISTRIBUTION OF K+
Includes:
Physiological: Keep plasma [K+] constant o Potassium supplements
Increases K+ uptake by stimulating Na/K-ATPase o ACE inhibitors
o Acute - turnover of Na/K-ATPase o K-sparing diuretics
o Chronic - no. of Na/K-ATPase o Heparin

Epinephrine K+ EXCRETION BY KIDNEYS
Acts within minutes Normal K+ intake: 100 mEq/L
Activates and 2-adrenergic receptors The kidneys excrete 90-95% of K+ diet intake
o release K+ from cells; important in Amounts of K+ lost in stool and sweat (5-10%)
hypokalemia mechanism Freely-filtered by the glomerulus
o 2 causes uptake of K+; important after Main determinant of urinary K+ excretion is K+
K+-rich meal and is released during stress secretion from the blood into distal tubule and
collecting duct system
Insulin Segment % K+ absorbed
Acts within minutes Proximal Tubule 67%
Most important hormone for K+ uptake Loop of Henle 20%
Stimulate K+ uptake after meal Distal Tubule 3%
Can be used to correct hyperkalemia Cortical Collecting Duct 9%


Aldosterone
K+ diet intake may reach 80% K+ urine
Acts after 1 hour
K+ diet intake may fall to 1% K+ urine
Stimulates urinary K+ secretion
Since the kidneys cannot reduce the K+ secretion
Ald may cause hypokalemia the same as Na+, hypokalemia may develop with
Ald may cause hyperkalemia K+-deficient diet


SALUNGA, JOEZELLE H. 1 of 4
 BERNE AND LEVY (5TH ED.) POTASSIUM, CALCIUM, PHOSPHATE
CHAPTER 37 HOMEOSTASIS

Cellular Mechanisms of K+ Transport An acute increase in aldosterone enhances the
by Distal Tubule and Collecting Duct activity of Na/K-ATPase but does not increase
Not completely understood K+ excretion
Intercalated cells may reabsorb K+ by H/K- o Aldosterone stimulates Na+ reabsorption
ATPase in the apical membrane water reabsorption
Pathway of K+ exit from IC cells is unknown tubular flow
K+ secretion
Secretion from blood into tubular fluid is a
two-step process involving: Glucocorticoids
1) K+ uptake across basolateral membrane by Na/K- Stimulate K+ excretion
ATPase Indirect effect: mediated by GFR tubular flow
o Creates high intracellular [K+]
provides the driving force for K+ exit ADH
across apical membrane K+ channels Stimulates Na+ uptake across apical membrane
Electrochemical gradient favors electrical potential difference across
downhill movement from apical apical membrane
Permeability is greater than driving force for K+ apical exit
basolateral membrane Does not change K+ secretion by these segments
2) Diffusion of K+ from the cell into the tubular fluid because it stimulates Na+ reabsorption:
water reabsorption
Three major factors controlling rate of K+ secretion: tubular flow
1) Activity of Na/K-ATPase
2) Driving force (electrochemical gradient) for K+ Factors Perturbing K+ Excretion
movement across apical membrane Flow of Tubular Fluid
3) Permeability of apical membrane to K+ Affects K+ secretion by altering driving force for
K+ exit across the apical membrane
Regulation of K+ Secretion tubular fluid rapidly (w/in minutes) stimulates
by Distal Tubule and Collecting Duct K+ secretion by DT and CT [vice versa]
Achieved mainly by alterations in K+ secretion by As K+ is secreted, [K+] of fluid increases
principal cells driving force for K+ exit
Major regulators of K+ secretion: rate of secretion
o Plasma [K+] tubular flow increases Na+ entering DT and CT
o Aldosterone Na+ reabsorption
o ADH less important Na/K-ATPase activity
K+ uptake across basolateral membrane
Plasma [K+] Diuretic drugs also increase tubular flow
Hyperkalemia stimulates within minutes enhances urinary K+ secretion
1) Stimulates Na/K-ATPase
K+ uptake across basolateral membrane Acid-Base Balance
intracellular [K+] Acute alterations in the pH od the plasma affect K+
electrochemical gradient secretion by DT and CT
K+ exit thru apical membrane Alkalosis increases H+ secretion
2) Increases permeability of apical m. to K+ Acidosis decreases K+ secretion
3) Stimulates aldosterone secretion by adrenal 1) Inhibits Na/K-ATPase
cortex, which also stimulates K+ secretion cell [K+]
4) Increases flow rate of tubular fluid driving force for K+ apical exit
Hypokalemia decreases K+ secretion 2) Reduces permeability of apical to K+
o Opposes mechanisms of hyperkalemia The effects of metabolic acidosis is time
dependent may inhibit of stimulate K+
Aldosterone excretion depending on duration of disturbance
A chronic elevation in plasma aldosterone o Chronic inhibits Na/K-ATPase
enhances K+ secretion by increasing amount of water, NaCl reabsorption
Na/K-ATPase in the principal cells augmented tubular flow
Increases K+ exit thru apical membrane decrease in ECF
Increases permeability of apical m. to K+ stimulate Aldosterone secretion
(also happens if caused by inorganic acids)


SALUNGA, JOEZELLE H. 2 of 4
 BERNE AND LEVY (5TH ED.) POTASSIUM, CALCIUM, PHOSPHATE
CHAPTER 37 HOMEOSTASIS

Ca2+ & Pi HOMEOSTASIS Parathyroid Hormone (PTH)
In a normal adult, Ca2+ and Pi renal excretion is most powerful effect on renal Ca2+ excretion;
balance by GI absorption responsible for maintaining Ca2+ homeostasis
If the plasma concentrations decline substantially, Secreted by parathyroid glands
the following return plasma conc. to normal: stimulated by plasma [Ca2+] (hypocalcemia)
o GI absorption reduced by hypercalcemia
o Bone resorption Increases plasma [Ca2+] by:
o Renal tubular reabsorption o Stimulating bone resorption
o Ca2+ reabsorption by kidneys
CALCIUM HOMEOSTASIS (Thick AL; DT)
Calcium plays a major role in different processes: o Stimulating production of calcitriol
o Bone formation Ca2+ GI reabsorption
o Cell division and growth Stimulates bone resorption
o Blood coagulation
o Hormone-response coupling Calcitriol
o Electrical stimulus-response coupling Similar mechanisms with PTH
99% of Ca2+ is stored in bones; 0.1% in ECF Production by proximal tubule stimulated by:
Total [Ca2+] in plasma is 10 mg/dL o Hypocalcemia
o Hypocalcemia Effect is secondary to PTH
Increases excitability of nerve o Hypophosphatemia
and muscle cells; Direct Pi Calcitriol
can lead to hypocalcemic tetany
characterized by muscle spasms Calcitonin
o Hypercalcemia Secreted by parafollicilar cells of thyroid gland
May lead to decreased stimulated by plasma [Ca2+] hypercalcemia
neuromuscular excitability, plasma [Ca2+] by stimulating bone formation
cardiac arrhythmias, lethargy, (Thick AL; DT)
disorientation, and even death
Ca2+ Transport along the Nephron
Ca2+ homeostasis depends on two factors: Normally, 99% of filtered Ca2+is reabsorbed
1) Total amount of Ca2+ in the body Segment % Ca2+ absorbed
Ca2+ is absorbed by GI though active, carrier- Proximal Tubule 70%
mediated transport mechanism stimulated by Loop of Henle 20%
calcitriol (metabolite of Vit D) Distal Tubule 9%
Ca2+ ingested in ave. diet 1,500 mg/day Cortical Collecting Duct <1%
Ca2+ lost in feces 1,300 mg/day
200 mg/day, but can increase
About 1% (200 mg/day) is excreted in urine
Net Ca2+ absorption by GI
to 600 mg/day
Ca renal excretion is equal to
2+ Proximal Tubule
200 mg/day
amount absorbed by GI Transcellular pathway
o 20% of PT reabsorption; active
2) Distribution of Ca2+ between bone & ECF o Ca2+ diffuses across the apical membrane
Regulated by three hormones: down a steep electrochemical gradient
o Parathyroid Hormone (PTH) also favors Ca2+ entry via Ca2+ channels
o Calcitriol o Ca2+ leaves via basolateral membrane
o Calcitonin Ca2+-ATPase and 3Na+/Ca2+-antiporter
Affected by acid-base balance Paracellular pathways
o 50% of plasma Ca2+ is ionized, 45% o 80% of PT reabsorption; passive
bound to plasma protein, 5% bound to o Occurs by solvent drag
several ions o Also driven by positive luminal voltage in
o Acidosis 2nd half f PT
increases percentage of ionized
calcium Protein-bound Loop of Henle
less susceptible to tetany Restricted to thick ascending limb
o Alkalosis via cellular and paracellular pathways
decreases percentage of ionized Similar to PT except Ca2+ solvent drag part
calcium Protein-bound Paracellular mechanism:
more susceptible to tetany

SALUNGA, JOEZELLE H. 3 of 4
 BERNE AND LEVY (5TH ED.) POTASSIUM, CALCIUM, PHOSPHATE
CHAPTER 37 HOMEOSTASIS

o Secondary to Na+ reabsorption and by generation of Proximal Tubule
lumen-positive transepithelial voltage
Change in Na+ will cause changes in Ca2+
mainly Transcellular pathway
reabsorption o Pi uptake across apical membrane via
2Na+/Pi symporter
Distal Tubules o Pi exits across basolateral membrane via
Tubule voltage is electronegative vs blood Ca2+ Pi/anion-antiporter
reabsorption is entirely active
Exclusively transcellular; similar to PT and LH: Regulation of Pi Reabsorption
o Uptake across apical membrane All act on the proximal tubule
o Exit across basolateral membrane Parathyroid Hormone (PTH)
Ca2+-ATPase and 3Na+/Ca2+-antiporter Stimulates cAMP production
Na+ and Ca2+ usually change in parallel but this is Inhibits Pi reabsorption in proximal tubule
not always the case: Dietary Pi intake
Reabsorption of Ca2+ and Na+ by distal tubule is Modulate Pi transport by:
independent and differentially regulated o altering transport rate of 2Na+/Pi-symporter
o increasing number of transporters
Example: thiazide diuretics inhibit Na+ reabsorption
Pi loading increases excretion [v/v]
but stimulate Ca2+ reabsorption. ECF Volume
Indirect effect
Regulation of Ca2+ Reabsorption Volume expansion increases excretion [v/v]
plasma Pi Acid-Base Balance
PTH Acidosis increases excretion
Ca2+ excretion [v/v] Alkalosis decreases excretion
Glucocorticoids
ECF volume
Allows DT and CT to secrete more H+ and generate
NaCl & Water reabsorption
more HCO3- for buffering
Ca2+ reabsorption; Ca2+ excretion [v/v] Inhibits proximal tubular reabsorption
Increase delivery of Pi to DT and CT
Pi HOMEOSTASIS * Absent in Addisons disease
Varying intake between 800-1,500 mg/day Growth Hormone
Decreases Pi excretion
Pi Homeostasis depends on two factors:
1) Amount of Pi in the body Integrated Hormone effect on Ca2+ and Pi
Determined by relative amount of Pi absorbed Parathyroid Hormone (PTH)
in GI minus excreted by kidneys Primarily stimulated by hypocalcemia
Stimulates bone resorption
Pi absorption occurs by both active and passive
Decreases urinary Ca2+ excretion
Pi absorption
Stimulates production of calcitriol
o increases as dietary Pi increases; Overall, a rise in plasma PTH increases plasma [Ca2+] but
o stimulated by calcitriol decreases plasma [Pi] [v/v]
Calcitriol
2) Distribution of Pi between ICF and ECF Stimulates Ca2+ and Pi GI reabsorption and bone
Regulated by three hormones: release
o Parathyroid Hormone (PTH) Decreases Ca2+ and Pi renal excretion
o Calcitriol The net effect is to increase increases plasma [Ca2+]
o Calcitonin stimulate bone-formation plasma [Pi]
Calcitonin
The release of Pi is always accompanied with Ca2+
Blocks bone resporption

Stimulates Ca2+ deposition in bone
Pi Transport along the Nephron Decreases Urinary Ca2+ excretion
Urinary Pi excretion increases to a value above Pi
GI absorption Net loss of Pi from the body Calcium-Sensing Receptor
Senses small changes in plasma [Ca2+]
Segment % Pi absorbed Where Ca2+ binds to in PTH-secreting cells
Proximal Tubule 80% o [Ca2+] inhibit PTH & Calcitriol, secrete
Distal Tubule 10% calcitonin
10% of filtered Pi is excreted Maintains Ca2+ homeostasis by direct regulation of
Ca2+ renal excretion

o [Ca2+] activates CaSR in TAL and DT
inhibits Ca2+ absorption


SALUNGA, JOEZELLE H. 4 of 4