L8 Renal Regulation Of K, Ca, And Phosphate Flashcards
Why is regulation of potassium important?
It’s role in the excitability of nerves and muscles (resting membrane potential depends on K concentration gradient)
ECF potassium is a function of what two variables?
Amount of K+ in the body (input = output)
Distribution of K+ between ICF and ECF
Most potassium is found _______
Inside cells rather than in the ECF (98%)
Therefore, changes in concentration are readily detected
Regulation of internal K+ is under the physiological control of what three hormones?
Epinephrine
Insulin
Aldosterone
In response to epinephrine, alpha-1 receptors cause a shift in K+ ______ of cells
Out of cells
May result in hyperkalemia
In response to epinephrine, ß-2 receptors stimulate K+ __________ cells
Uptake into cells
May cause hypokalemia
ß-2 antagonists block this action and can cause HYPERkalemia
How does insulin regulate internal K+ distribution?
Insulin increases K+ uptake into cells
Responsible for dietary uptake of K+ into cells after a meal
Also stimulates Na/K ATPase
How does Aldosterone regulate internal K+ distribution?
Aldosterone increases K+ uptake into tubule cells and increases K+ excretion
Also stimulates Na/K ATPase
Other non-hormonal factors regulating the internal K+ balance
Hyperosmolarity (ie exercise and cell lysis) —> drives K+ out of cells —> hyperkalemia
Insulin and ß agonists drive K+ into cells —> hypokalemia
Acid-base factors influencing internal K+ balance
Acidosis —> movement of K+ out of cells
Alkalosis —> movement of K+ into cells
Generalizations for K+ balance
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
Factors that increase K+ secretion
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
K+ secretion also increases when ______ load to the distal nephron increases
Na+
Increased sodium load to principal cells stimulates the Na/K ATPase —> increases intracellular K+ concentrations
What is the link between loop diuretics and thiazides and kaliuresis?
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
In high K+ diets, _______ is stimulated by high plasma K+ and promotes K+ secretion
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
Summarize the control of K+ excretion by aldosterone…
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
The homeostatic response to a low K+ diet?
Decrease K+ excretion
Proximal tubule and LOH will reabsorb 87% of the filtered K+
Remaining K+ will be reabsorbed in the distal nephron
Where does the K+ reabsorption occur in the distal nephron?
In the alpha-intercalated cells
K+ is reabsorbed in exchange for H+ secretion
K+ diffuses across the basolateral membrane back to the blood
Why is it so important to regulate Calcium?
Plays a major role in: • Bone formation •Cell growth/division • Blood coagulation •Hormone-response coupling • Excitation-contraction coupling
Where is calcium stored in the body?
99% in bone
1% in the ICF
0.1% in the ECF
Normal plasma Ca2+ level
2.5 mM = 5 mEq/L = 0.1 mg/ml
The three forms of Ca2+ in the plasma
50% ionized Ca2+ (the biologically active form)
10% complexed to anions (ie CaPO4)
40% bound to plasma proteins
How is Ca2+ handled by the kidneys?
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
Sites of Ca2+ reabsorption in the kidneys
Proximal tubule - 67% Thick ascending limb - 25% Distal tubule - 5-10% Collecting duct - <5% Excreted - 1%
By what mechanism is Ca2+ reabsorbed in the proximal tubule?
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
_________ interfere with Ca2+ reabsorption and are used to treat hypercalcemia
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
How is Ca2+ reabsorbed in the distal tubule?
Across apical membrane (via Ca2+ channels)
Across the basolateral membrane via either active transport (Ca2+-ATPase) or Na/Ca2+ exchange
Parathyroid hormone stimulates Ca2+ uptake in the ________
Distal tubule
Mediated by cAMP
__________ increase Ca2+ from the luminal fluid and should not be given to patients with hypercalcemia
Thiazide diuretics
Thiazides inhibit NaCl reabsorption but stimulate Ca2+ reabsorption
Thiazides decrease [Na+] which increases inward movement of Na+ via the Na/Ca2+ exchanger
Why do we regulate Phosphate?
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
How much of plasma PO4 is protein-bound?
10%
_____ of phosphate is stored in the bones
85%
________% of plasma PO4 is filterable at the glomerulus
90-95%
______% is reabsorbed in either the convoluted or straight proximal tubule
85%
The amount of PO4 reabsorbed in the LOH, distal tubule, and CD is ….
Negligible.
Most is reabsorbed in the proximal tubule
____% of PO4 is excreted
15%
Important buffer anion in urine
Role of PTH in PO4 balance
Decreased plasma ionized Ca2+ —> Increased PTH
Increased PTH —> decreased PO4 reabsorption in the proximal tubule —> increased PO4 excretion
