L8 Renal Regulation Of K, Ca, And Phosphate

Question 1

Why is regulation of potassium important?

Answer 1

It’s role in the excitability of nerves and muscles (resting membrane potential depends on K concentration gradient)

Question 2

ECF potassium is a function of what two variables?

Answer 2

Amount of K+ in the body (input = output)

Distribution of K+ between ICF and ECF

Question 3

Most potassium is found _______

Answer 3

Inside cells rather than in the ECF (98%)

Therefore, changes in concentration are readily detected

Question 4

Regulation of internal K+ is under the physiological control of what three hormones?

Answer 4

Epinephrine
Insulin
Aldosterone

Question 5

In response to epinephrine, alpha-1 receptors cause a shift in K+ ______ of cells

Answer 5

Out of cells

May result in hyperkalemia

Question 6

In response to epinephrine, ß-2 receptors stimulate K+ __________ cells

Answer 6

Uptake into cells

May cause hypokalemia

ß-2 antagonists block this action and can cause HYPERkalemia

Question 7

How does insulin regulate internal K+ distribution?

Answer 7

Insulin increases K+ uptake into cells

Responsible for dietary uptake of K+ into cells after a meal

Also stimulates Na/K ATPase

Question 8

How does Aldosterone regulate internal K+ distribution?

Answer 8

Aldosterone increases K+ uptake into tubule cells and increases K+ excretion

Also stimulates Na/K ATPase

Question 9

Other non-hormonal factors regulating the internal K+ balance

Answer 9

Hyperosmolarity (ie exercise and cell lysis) —> drives K+ out of cells —> hyperkalemia

Insulin and ß agonists drive K+ into cells —> hypokalemia

Question 10

Acid-base factors influencing internal K+ balance

Answer 10

Acidosis —> movement of K+ out of cells

Alkalosis —> movement of K+ into cells

Question 11

Generalizations for K+ balance

Answer 11

Input = output for balance to occur

Dietary K+ is variable (50-150 mEq/day)

Transport in the proximal tubule and loop of Henle DOES NOT CHANGE in the face of increased or decreased total body K+

Physiological regulation of K+ is in the distal tubule and collecting duct

Question 12

Factors that increase K+ secretion

Answer 12

Increased dietary intake (more K+ enters principal cells from ECF so intracellular K+ increases)

When aldosterone is present

During alkalosis (high pH) b/c intracellular K+ increases due to efflux of H+ from cells

At high urine flow rates

Question 13

K+ secretion also increases when ______ load to the distal nephron increases

Answer 13

Na+

Increased sodium load to principal cells stimulates the Na/K ATPase —> increases intracellular K+ concentrations

Question 14

What is the link between loop diuretics and thiazides and kaliuresis?

Answer 14

Increased delivery of Na+ to distal nephron will increase K+ loss (loops)

Increased Na+ entry via apical channel stimulates the Na/K ATPas (thiazides)

Both mechanisms increase the intracellular [K+] and K+ secretion

Question 15

In high K+ diets, _______ is stimulated by high plasma K+ and promotes K+ secretion

Answer 15

Aldosterone

Stimulation of the basolateral membrane Na/K-ATPase in principal cells —> increased luminal membrane permeability to K+

Apical K+ channel up-regulation in addition to the Na/K-ATPase

Question 16

Summarize the control of K+ excretion by aldosterone…

Answer 16

Low plasma volume —> increased Renin secretion —> increased plasma renin —> increased plasma angiotensin II

Increased plasma angiotensin II combined with increased plasma potassium —> increased aldosterone secretion —> increased plasma aldosterone —> tubular reabsorption of sodium and decreased sodium excretion AND tubular secretion of potassium and increase potassium excretion

Question 17

The homeostatic response to a low K+ diet?

Answer 17

Decrease K+ excretion

Proximal tubule and LOH will reabsorb 87% of the filtered K+

Remaining K+ will be reabsorbed in the distal nephron

Question 18

Where does the K+ reabsorption occur in the distal nephron?

Answer 18

In the alpha-intercalated cells

K+ is reabsorbed in exchange for H+ secretion

K+ diffuses across the basolateral membrane back to the blood

Question 19

Why is it so important to regulate Calcium?

Answer 19

Plays a major role in:
• Bone formation
•Cell growth/division
• Blood coagulation
•Hormone-response coupling
• Excitation-contraction coupling

Question 20

Where is calcium stored in the body?

Answer 20

99% in bone

1% in the ICF

0.1% in the ECF

Question 21

Normal plasma Ca2+ level

Answer 21

2.5 mM = 5 mEq/L = 0.1 mg/ml

Question 22

The three forms of Ca2+ in the plasma

Answer 22

50% ionized Ca2+ (the biologically active form)
10% complexed to anions (ie CaPO4)
40% bound to plasma proteins

Question 23

How is Ca2+ handled by the kidneys?

Answer 23

Ca2+ is filtered and reabsorbed
• 60% of plasma Ca2+ is filtered (40% is bound)
• FL = GFR(Pca)(0.6) = (125)(0.1)(0.6) = 7.5 mg/min

Reabsorption occurs throughout the nephron (99%) except the descending limb of LOH

Only 1% of filtered Ca appears in the urine

Question 24

Sites of Ca2+ reabsorption in the kidneys

Answer 24

Proximal tubule - 67%
Thick ascending limb - 25%
Distal tubule - 5-10%
Collecting duct - <5%
Excreted - 1%

Question 25

By what mechanism is Ca2+ reabsorbed in the proximal tubule?

Answer 25

Passive reabsorption

Coupled to Na+ (factors that affect Na+ reabsorption also affect Ca2+ - when Na+ uptake is high, so is Ca2+)

Reabsorbed through paracellular route

Question 26

_________ interfere with Ca2+ reabsorption and are used to treat hypercalcemia

Answer 26

Loop diuretics

The lumen of the thick ascending limb of LOH has a positive potential that drives Ca2+ reabsorption

Ca2+ also enters via paracellular pathway

Question 27

How is Ca2+ reabsorbed in the distal tubule?

Answer 27

Across apical membrane (via Ca2+ channels)

Across the basolateral membrane via either active transport (Ca2+-ATPase) or Na/Ca2+ exchange

Question 28

Parathyroid hormone stimulates Ca2+ uptake in the ________

Answer 28

Distal tubule

Mediated by cAMP

Question 29

__________ increase Ca2+ from the luminal fluid and should not be given to patients with hypercalcemia

Answer 29

Thiazide diuretics

Thiazides inhibit NaCl reabsorption but stimulate Ca2+ reabsorption

Thiazides decrease [Na+] which increases inward movement of Na+ via the Na/Ca2+ exchanger

Question 30

Why do we regulate Phosphate?

Answer 30

PO4 is an important component of organic molecules such as DNA, RNA, and ATP

Also a major component of bone

Urinary PO4 is an important buffer in acid-base balance

Question 31

How much of plasma PO4 is protein-bound?

Answer 31

10%

Question 32

_____ of phosphate is stored in the bones

Answer 32

85%

Question 33

________% of plasma PO4 is filterable at the glomerulus

Answer 33

90-95%

Question 34

______% is reabsorbed in either the convoluted or straight proximal tubule

Answer 34

85%

Question 35

The amount of PO4 reabsorbed in the LOH, distal tubule, and CD is ….

Answer 35

Negligible.

Most is reabsorbed in the proximal tubule

Question 36

____% of PO4 is excreted

Answer 36

15%

Important buffer anion in urine

Question 37

Role of PTH in PO4 balance

Answer 37

Decreased plasma ionized Ca2+ —> Increased PTH

Increased PTH —> decreased PO4 reabsorption in the proximal tubule —> increased PO4 excretion