K Regulation Flashcards
What is renal secretion?
moving a substance from the blood into the lumen of a nephron
What is the mechanism through which secretion of substances takes place?
Active pumps on the basolateral side of the nephron tubule cell, establishing a gradient (high inside cell)
Apical part of a lumen cell = ? Basolateral = ?
Apical = The part that faces the tubule lumen
Basolateral = the part that faces the interstitium
Secretion of organic cations through the tubule cell is different from secretion of organic anions. Why?
Since the electrical force on the ion from the negative membrane potential favors movement of the cation into the cell, from the interstitial fluid.
What is the significance of the fact that many molecules in the blood use the same transporter to be secreted into the lumen of the nephron?
secretion of one substance might be decreased in the presence of one of its competitions for the carrier protein
Why is it that a substance that is secreted may not always stay in the tubular lumen? (2)
There can be back leak through the “tight” junctions
pH of urine can affect charge, and thus solubility of substance
What happens with ASA when the urine is highly acidic (as in acidemia)?
Since ASA is an organic acid, low pH will protonate it, and cause it to leak back in
How can you treat overdose on ASA via the renal tubules?
Give lots of bicarb
Organic cations are also called what?
Organic bases
If the dissociated state of an organic base predominates, what will predominate: excretion or reabsorption?
Excretion
Acidification of urine increases or decreases reabsorption of organic bases?
decreases
What are atropine, morphine and cimetidine–organic acids or bases?
Organic bases
Excretion = ?
Secretion + filtration
Why is PAH used to demonstrate renal plasma flow?
For the most part, it mostly cannot reabsorbed, only filtered and secreted
What is the point at which the renal nephrons secrete the maximum amount of a substance?
Transport maximum
What is the equation for renal plasma flow?
[(Upah)(V) / Ppah ]/ (1-hematocrit)
Why isn’t PAH perfect?
Some is absorbed from the nephron
How do you calculate the filtration fraction?
GFR/ ERFP
What is the filtration fraction?
The percent of the plasma delivered to the kidneys that is filtered
Why is K so important to homeostasis?
Establishes membrane potentials (like in the heart)
Is K bound to plasma proteins? What is the consequence of this?
No, thus it is freely filtered at the glomerulus
Where does most K reabsorption take place? How regulated is this?
Ascending loop of Henle
Essentially unregulated
What/where are the regulated parts of K reabsorption?
Distal tubule and collecting duct
What happens to the tubules in hyperkalemia?
High K+ stimulates the Na/K+ATPase pump on basolateral surface. This transports K+ into the tubule cell. K+ can then flow down its electrochemical gradient through open K+ channels in the luminal membrane.
What is the chemical that stimulates K secretion (besides K itself)?
Aldosterone
What happens to the renal tubule in hypokalemia?
the Na+/K+ATPase pump is inhibited. The collecting duct intercalated cells have a K+ resorption pump on their luminal membrane and this pump is continually active.
True or false: The collecting duct intercalated cells have a K+ resorption pump on their luminal membrane and this pump is continually active. Only the Na/K pump on the basolateral surface of tubule cells are regulated
True
What is the main effect of aldosterone on K reuptake/secretion?
increase the number of active epithelial sodium channels (ENaCs) in the collecting ducts, increasing the reabsorption of Na+ and increase the secretion of K+.
What is the effect of ANP on ENaC? What is the effect on plasma [K]?
Inhibited, leading to increased [K]
In what cells are the Na/K pumps regulated within a nephron?
Principle cells
What are the two ways discussed in lecture that increases aldosterone production?
- Increased plasma [K]
2. Activation of renin-angiotensin system
What are the five effects of aldosterone?
- Increase the amount of Na/K-ATPase in the basolateral membrane
- Increase expression of EnaC in apical membrane
- Elevate SGK1 to further 1 and 2
- Stimulates CAP1 to activate ENaC
- Increases K channels
What is the effect of ouabain?
inhibits Na/K pump
What is the effect of a diuretic? What does this do to K secretion?
inhibits the reabsorption of water at some point in the nephron, causing water and K to be secreted
What is the effect of loop diuretics?
Block the Na/K/Cl pumps in the thick ascending loop of Henle on the luminal side. This leads to a decrease in water reabsorption, because there is a lower gradient of solutes
What lab value (discussed in this lecture specifically) should be closely monitored with patients on diuretics?
[K]
What is the MOA of thiazide diuretics?
inhibit NaCl reabsorption in the early distal tubule, thus inhibiting water following
What causes the increase in K secretion to increased flow?
Cilia bending causes cascade to be activated, Ca activation, and K channels recruited
What are the potassium sparing diuretics? How do they work?
Aldosterone inhibitors, which will decrease Na and water reabsorption
What is a complication of using aldosterone inhibitors?
Hyperkalemia
What is the effect of metabolic alkalosis on the Na/K ATPase on the basolateral membrane of principal cells of the late distal convoluted tubule and collecting ducts? What happens to the intracellular [K]?
Increases x2
What are the three loop diuretics?
Furosemide
Ethacrynic acid
Bumetaide
Which side of the principal cells is the Na/K ATPase on: the basolateral or the luminal side?
Basolateral
Why does the reabsorption of other positive ions decrease in response to the presence of loop diuretics?
The drug lowers the positive Electrochemical gradient in the lumen
What is the major source of K loss in the nephrons: the inactivation of the pump or the increase flow, leading to increased K excretion
Increased flow
What causes the increased K excretion seen in metabolic alkalosis?
Increases the Na/K ATPase action in the distal tubule, increasing K intake into the cell from the ECF, and thus causing it to flow into the lumen
Chronic metabolic alkalosis + decreased ECF results in a significant increase in K excretion. Why?
Increases aldosterone d/t lower BP. This activates the Na/K pump
What is the effect of acidosis on [K]? How?
Sometimes causes hyperkalemia.
Caused by an intake of H into cells, leading to outflow of K to maintain electric neutrality
What is the effect of aldosterone on K secretion? How?
Increases via increasing the Na/K pump action
What controls secretion of aldosterone?
plasma [K]
What is Conn syndrome, and how does it relate to K secretion?
Causes excess aldosterone, thus increases K secretion
What is Addison’s disease, and how can it cause Hyperkalemia?
Inhibition of aldosterone, leading to less function of the Na/K pump
What is the effect of beta blockers on K?
May cause hyperkalemia
What is the effect of catecholamines on plasma [K]?
Hypokalemia
What is the main cell type that is involved in K regulation?
Principle cells of the distal tubule
What are the three ways that an increased plasma [K] will increase K secretion?
- Increases Na/K ATPase activity
- Increased gradient potential
- Increased aldosterone synthesis
