Regulation of Solutes/Ions Flashcards
Renal Control of Potassium
-Results?
Changes in cardiac function, ECG changes
Effects on K concentration on ECGs
Slide 10
Factors affecting movement on K+ between intracellular and extracellular pools
-ICF (cells)–> ECF (movement out of cells)
- Hypokalemia
- Acidemia
- Ischemia (cell damage)
- alpha-adrenergic agonists
- Heavy exercise
Factors affecting movement on K+ between intracellular and extracellular pools
-ECF–> ICF (cells) (movement into cells)
Hyperkalemia
Alkalemia
Beta-adrenergic agonists
Insulin
Factors affecting movement on K+ between intracellular and extracellular pools
-ECF–> ICF (cells) (movement into cells)-Hyperkalemia is seen in patients with what common disease?
Diabetes
When a patient is alkalotic, what is happening to:
- H?
- Na, K?
-H+ is being pumped out of the cells (to compensate for the decreased H+ in the ECF)
-Na and K are being pumped into the cells
(opposite for acidotic)–>hypokalemic
Renal tubular handling of K
-Where is it reabsorbed?
-Mostly in the PT but also in the thick ascending limb via the Na, K, 2Cl cotransporter)
Renal tubular handling of K
-Where is physiological control exerted?
- In the CD
- Principal cells either reabsorb or secrete K depending on body’s K balance
Five factors which affect K secretion in CD?
- Extracellular K concentration
- Na reabsorption
- Luminal fluid flow rate (Na and water delivery)
- Extracellular pH
- Aldosterone
Five factors which affect K secretion in CD
-Na reabsorption?
Negative luminal voltage ‘attracts’ K
Five factors which affect K secretion in CD?
-Luminal fluid flow rate?
Dilution of secreted K resulting in conc gradient
Five factors which affect K secretion in CD?
-Extracellular pH?
K and H exchange across cell membranes
Five factors which affect K secretion in CD?
-Aldosterone?
Stimulates K secretion in CD to maintain electroneutrality when Na is reabsorbed
General rule of thumb
-Out of Na, H, and K-When one of these three is being absorbed?
The other 2 are going out of the cell to balance it out
What happens to urinary K excretion as plasma K concentration increases?
Urinary K excretion increases
Tubular flow rate affects K secretion in the distal nephron (graph)
-Patients on loop diuretics sometimes need to be supplemented with?
Potassium
Situations that alter K handling
-MOA of most diuretics?
Most classes of diuretics increase Na and volume delivery to late DT and CD which increases K secretion
Situations that alter K handling
-Low sodium diet?
Less Na delivery to late DT, CD–> less K excretion–>may cause hyperkalemia
Clinical application-How might hyperkalemia be treated?
- By increasing downstream delivery of Na to the DT/CD
- Results in increased Na reabsorption and K secretion
Amount of potassium secreted in an acidotic patient versus an alkalotic patient?
An acidotic patient would secrete less potassium than normal (opposite for alkalotic)
Effect of aldosterone on K?
Aldosterone stimulates K secretion in DT and CD
Effect of increased plasma K concentration on aldosterone?
Increased plasma concentration stimulates aldosterone secretion
2 main presenting symptoms of hyperaldosteronism (Conn’s syndrome)?
Hypokalemia and metabolic alkalosis
What would be the plasma Na of a patient with hyperaldosteronism?
It would be normal or on the high end of normal (not extremely high) because water is being absorbed along with the sodium
Disorders of aldosterone secretion
- Primary hyperaldosteronism (Conn’s syndrome)
- Due to?
- What happens to K secretion?
- Consequence?
- Aldosterone secreting tumor in adrenal cortex
- Inappropriately stimulated K secretion–>hypokalemia
Disorders of aldosterone secretion
- Hypoaldosteronism (Addison’s disease)?
- Caused by?
- What happens to K secretion?
- Consequence?
- Destruction of adrenals (no aldosterone secreted)
- Decreased K secretion in CD–>hyperkalemia
Disorders of aldosterone secretion
- Hypoaldosteronism (Addison’s disease)
- What would the sodium level be?
Low sodium level
Practice on slide 28
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Diuretics
-What are they?
Drugs that increase urine excretion by inhibiting tubular solute and water reabsorption (increasing excretion)
Diuretics
-Purpose?
To help eliminate excess volume to treat volume overload disorders (e.g. edema, CHF)
Different classes of diuretics
- Osmotic diuretics
- MOA?
- Example?
- Inhibit reabsorption of water and, secondarily, Na
- Example-mannitol
Different classes of diuretics
- Carbonic anhydrase inhibitors
- MOA?
- Example?
- Inhibit NAHCO3 reabsorption
- Example-Acetazolamide
Where do osmotic diuretics and carbonic anhydrase inhibitors act in the nephron?
Proximal tubule
Loop diuretics
-Where in the nephron do they act?
Loop diuretics act at the loop of Henle
Loop diuretics
-MOA?
- Inhibit Na, K, 2Cl cotransporter by competing for Cl
- Increases total RBF and dissipates high solute concentration of medullary interstitium
- Lessens water reabsorption in descending limb and medullary CD
Loop diuretics
-Caveat?
Powerful: require careful medical supervision
Loop diuretics
-Examples?
Furosemide (lasix), bumetanide (bumex), ethacrynic acid
Thiazide diuretics
-Where do they act in the nephron?
DCT
Thiazide diuretics
-MOA?
- Inhibit Na, Cl cotransport
- Increase Na, Cl, and K excretion
- Results in decreased Ca excretion
Thiazide diuretics
-Example?
Hydrochlorothizazide
“Potassium-sparing” diuretics
-Where do they act in the nephron?
Collecting duct
“Potassium-sparing” diuretics
- MOA? - Often used in combination with?
- Inhibit Na reabsorption and K secretion
- Often used in combination with other diuretic classes that increase K excretion
“Potassium-sparing” diuretics
-Examples?
-Amiloride, triamterene, spironolactone
“Potassium-sparing” diuretics
-Triamtrene-MOA?
Blocks Na channels
“Potassium-sparing” diuretics
-Spironolactone-MOA?
Aldosterone antagonist
Summary of diuretics
Slide 34
Renal control of Calcium
-Importance of EC Ca?
- Affects activity of excitable tissues: nerve, muscle, myocardium
- Enzyme cofactor, component of bone, cell signaling, blood clotting
Ca can damage action potentials by?
-Ca can dampen action potentials by blocking Na channels
Renal Control of Potassium
-What are the effects of extracellular K concentration?
Extracellular K concentration affects membrane potential and excitability of muscle and nerve tissue
Low EC Ca can induce?
Hypocalcemic tetany
Ca is required for?
Neuromuscular transmission
Active vs inactive Ca?
- 45% of plasma Ca is protein-bound-inactive
- ONLY free Ca is biologically active
What is the Ca concentration in Bowman’s capsule? Why?
Only half of Ca in blood can be filtered because half of Ca is protein bound and proteins cannot be filtered through the glomerulus
Effect of plasma pH on free Ca?
H compete with Ca for binding sites on plasma proteins
Acidemia-increased H–>?
Increased free Ca in plasma (opposite for alkalemia)
Patient with acidosis is at risk for?
Hypercalcemia (alkalotic patient is at risk for hypocalcemia)
How does EC Ca affect the myocardium?
Affects contractile strength
Hypocalcemia-What does PTH do when released:
-3 MOA?
- Causes the kidneys to activate vitamin D (calcitriol)
- Causes GI tract to reabsorb more Ca from diet
- Causes resorption of bone by osteoclastic activity
Where is the majority of Ca reabsorbed?
PCT
Mechanism of PT Ca reabsorption
-2 routes?
- Paracellular-between the cells
- Transcellular-intracellular calcium is very low compared to tubular fluid-goes down concentration gradient
Paracellular Ca reabsorption in thick ascending limb of Henles loop
-Driven by?
Positive transepithelial potential
Paracellular Ca reabsorption in thick ascending limb of Henles loop-Driven by positive transepithelial potential
-What effects will loop diuretics have on this process?
Abolishes the positive transepithelial potential and the reabsorption of Na, K, Ca, Mg and NH2 decreases
-This is why loop diuretics are so powerful-gets rid of a lot of different electrolytes
Reabsorption of which ions are particularly dependent on the positive transepithelial potential?
Ca and Mg
Transcellular Ca reabsorption in distal tubular cells (explained in lecture)
- Epithelial calcium channels are vitamin D dependent
- So when PTH is released and vitamin D is activated it activates these channels to reabsorb Ca into the cell
- Once in the cell, Ca binds to calbindin and is then reabsorbed into the capillary via Ca ATPase and/or Ca, Na exchanger
Hypocalcemia-Parathyroid gland senses this
-What does parathyroid gland do?
-When parathyroid gland senses low Ca it releases PTH
Patients on thiazide diuretics are at risk for?
Hypercalcemia
Physiological control of tubular Ca reabsorption
-Where in the nephron is control exerted?
Control is exerted in the thick ascending limb and DCT
Physiological control of tubular Ca reabsorption
-Reabsorption is stimulated by?
PTH, calcitriol (vit. D3), and calcitonin
Physiological control of tubular Ca reabsorption
-Decreased plasma Ca induces cells parathyroid gland to?
secrete PTH
Overall effect of PTH?
Increase EC Ca
As plasma Ca increases, what happens to PTH?
Decreases
As Plasma Ca increases, what happens to calcitonin (probably don’t need to know)?
Increases
PTH and calcitriol flow chart
slide 46
What can happen to patients with renal disease if it goes on long enough?
Since the renal tissue is damaged the kidney is unable to activate vitamin D and inhibits the body’s ability to reabsorb Ca via the tubule
This leads to increased PTH driven resorption of bone and thus the patient’s bones become fibrotic and diseased-secondary hyperparathyroidism
Transcellular Ca reabsorption in distal tubular cells
-MOA of thiazide diuretics (from slide)?
-Inhibit the Na, Cl symporter in early DCT–>intracellular Na decreases–>enhances activity of Na, Ca exchanger creating an increased driving force for Ca reabsorption and Na excretion
Mechanism of proximal tubular phosphate reabsorption
- How does it get into the cell?
- How does it get into the blood?
- Most of it is by a sodium cotransporter-depends on sodium gradient-this gets the phosphate into the cell
- Then it is sent into the blood by an anion counter transporter-anion goes from blood into the cell phosphate goes from cell into blood
Proximal tubular phosphate reabsorption
-Reabsorption of phosphate is inhibited by?
PTH-decreases Tm Increases excretion (decreases absorption)
Mg handling by nephron
-Bulk of the filtered Mg is reabsorbed in the?
Thick ascending limb (by paracellular movement)
How is the transepithelial potential established and how does this apply to Mg reabsorption?
By potassium leak channels-positive charge builds up in the tubular urine and drives magnesium between the cells and helps it reabsorb (they repel each other b/c they are like charges)
Effect of loop diuretics on the transepithelial potential and their MOA?
Increase flow? and decrease the transepithelial potential (pos charge)
Renal control of phosphate
-In what part of the nephron is the majority of phosphate reabsorbed?
PCT
