Renal Transport Mechanisms Flashcards
What fraction of filtered water is reabsorbed by the PT?
2/3
Why do the lines for Na and K superimpose on the 1.0 line on TF:P graphs?
They are reabsorbed at the same rate as water
What does it mean to have a TF:P ratio of >1?
More water is reabsorbed than solutes, or solute is being secreted
What does it mean to have a TF:P ratio of <1?
More solute is being reabsorbed than water
Sodium uptake across the apical membrane in the early PT is coupled with another molecule. What molecules might sodium be reabsorbed with?
What about exchanged with?
Primarily with HCO3
Can also be with glucose, amino acids, Pi, and lactate
May be reabsorbed in exchange for H+ or organic solutes
The reabsorption of Na and its buddies in the PT generates a transtubular osmotic gradient. Osmolality of tubular fluid is slightly ______ than that in the ISF outside the basolateral membrane, which provides the driving force for ______ diffusion of water from the tubule to ISF and the blood.
Lower
Passive
More water than Cl is reabsorbed in the early PT, so tubular [Cl] rises by the time we come to the late PT. How does this drive reabsorption of Na and Cl?
By creating a positive transepithelial potential difference, driving paracellular reabsorption of Na and Cl
There is also a modest concentration gradient created by sodium and water reabsorption, as Cl and urea become more concentrated along the length of the PT
Na+uptake across the apical membrane of the LATE PT is coupled with ____ via _________ route
[what other transporters must be operating simultaneously?]
Cl; transcellular
Requires operation of parallel transports in Na/H antiporter and Cl-base antiporters
What forces push water from interstitial fluid into the peritubular capillary?
Hydrostatic pressure pushes fluid and solute from ISF into peritubular capillary space
In addition, protein oncotic pressure in peritubular capillary is elevated bc of glomerular filtration, which helps pull water in
Describe transport mechanism and cellular path for glucose reabsorption
Secondary active transport along trancellular path across SGLT in apical membrane using gradient set up by Na/K ATPase in basolateral membrane
Glucose then exits through basolateral membrane via facilitated diffusion through GLUT transporter
What happens in filtered amount of glucose exceeds a certain rate?
If filtered load exceeds a certain rate, SGLTs become saturated and capacity to reabsorb all glucose is exceeded (Tm); glucose appears in the urine
[same principle applies to protein]
Where in the nephron is secretion most active?
PT
Describe transporters utilized for organic anion secretion
OATs in basolateral membrane - OA’s are taken across basolateral membrane in exchange for a-KG moving down its gradient.
OA’s cross the apical membrane via ATP dependent MRP2/4 or BCRP; or via OAT4 in exchange for a-KG
Describe transporters utilized for organic cation secretion
OCT’s in basolateral membrane - cations taken across basolateral membrane driven by magnitude of cell-negative potential difference
OCT’s in apical membrane (ATP dependent), or in exchange for H+
T/F: PAH is both filtered and secreted
True
What type of molecule is creatinine, and what transporters does it utilize?
An organic cation; utilizes organic cation and anion transporters
What occurs in the kidneys with aspirin poisoning, and how might this be treated?
Aspirin has a weak acid metabolite (salicylic acid), dropping the pH of the urine.
Treatment goal is to make the urine more alkaline with sodium bicarb in order to increase ionization of salicylic acid and increase its excretion from the body. Activated charcoal and IV sodium bicarb are used to keep HCO3 from being reabsorbed, or to take more H+ out of the tubule.
[ionization makes it harder for the salicylic acid to be reabsorbed back into the cell]
What are some factors the shift K+ into cells (thus potentially causing hypokalemia)
Insulin
Aldosterone
B-adrenergic stimulation
Alkalosis
What are some factors that shift K+ out of cells (thus potentially causing hyperkalemia)
Insulin deficiency Aldosterone deficiency B-adrenergic blockade Acidosis Cell lysis Strenuous exercise Increased extracellular fluid osmolality
Variations in [K+] alter membrane potential of skeletal muscle and can result in cardiac arrhythmias. What effect does hyperkalemia have on these 2 cell types?
Skeletal muscle: increases resting potential, thus making it easier to generate a muscle contraction
Cardiac muscle: PR interval prolonged, T wave “tenting”, P wave may become indiscernable, possible Vfib. Becomes lethal at high concentrations
Variations in [K+] alter membrane potential of skeletal muscle and can result in cardiac arrhythmias. What effect does hypokalemia have on these 2 cell types?
Skeletal muscle: shifts resting potential more negative, making muscle contraction more difficult
Cardiac muscle: flattened T wave, may depress ST segment
What is reabsorbed vs. secreted by the principal cells?
Reabsorb: Na+ and H2O
Secrete: K+
What is reabsorbed vs. secreted by the alpha-intercalated cells?
Reabsorb: K+ and HCO3
Secrete: H+
What is reabsorbed vs. secreted by the beta-intercalated cells?
Reabsorb: H+ and Cl-
Secrete: K+ and HCO3-
What are the 3 most important factors that stimulate potassium secretion?
- Increased ECF [K+]
- Aldosterone
- Increased tubular flow rate
What are the 2 most important factors that stimulate potassium reabsorption?
- K+ deficiency, low K+ diet, hypokalemia
2. K+ loss through SEVERE diarrhea
Describe the K+ shift caused by acidosis
Decreased activity of Na/K pump
Decreased [K] in the cell
Decreased passive diffusion of K into tubule lumen
Decreased K+ channels
Decreased K+ secretion
End result = hyperkalemia
Acute acidosis causes a decrease in potassium secretion with the end result of hyperkalemia. What are the effects of chronic acidosis on potassium?
Chronic acidosis stimulates K+ secretion
[because chronic acidosis decreases reabsorption of water and solutes by the PT by inhibiting the Na/K pump which increases tubular flow to DT and CD. Meanwhile RAAS is stimulated d/t lack of water reabsoprtion and subsequent decrease in ECF volume. These changes offset the reabsorptive effects of acute acidosis and K+ secretion rate rises]
What effects do hypoalbuminemia vs. hyperalbuminemia have on plasma Ca?
Hypoalbuminemia increases plasma Ca
Hyperalbuminemia decreases plasma Ca
T/F: in alkalosis, there is more free calcium in circulation
False; this is true of acidosis
Alkalosis results in more calcium bound to plasma proteins
Alkalosis results in more calcium bound to plasma proteins, which predisposes to what condition?
Hypocalcemic tetany
What effect does a decreased [Ca++] have on PTH levels? What are the downstream effects?
Decreased [Ca] –> increased PTH
Increased PTH increases Vit D3 activation, increases Ca release from bones, and increases renal Ca reabsorption
What is the mechanism of reabsorption of Ca in the proximal tubule?
Primarily paracellular
May also be transcellular by diffusion gradient into cell, exits via Ca ATPase and Na/Ca antiporter
What change in ECF causes an increase in Ca reabsorption in the PT?
Volume contraction
Describe Ca reabsorption in TAL
Primarily paracellular; reabsorption parallels Na
[dependent upon TEPD - lumen positive voltage; ADH stimualtes reabsorption]
How are loop diuretics able to treat hypercalcemia?
They inhibit Na reabsorption in the TAL, thus reducing the TEPD, reducing Ca paracellular reabsorption (increasing Ca excretion)
The DT has a lumen-______ transepithelial voltage. Ca reabsorption is active transcellular transport; it crosses the apical membrane via _______ and the basolateral membrane via Na/Ca exchanger
Negative; TRPV5
What 2 compounds stimulate Ca reabsorption in the DT?
PTH and thiazide diuretics (also Vit D and calcitriol)
What effect does acidemia have on TRPV5 in the DT?
Acidemia increases Ca excretion by inhibiting TRPV5
[alkalemia decreases Ca excretion by stimulating TRPV5]
Calcitonin’s 3 effects on calcium renal regulation
Opposes PTH
Stimulated by hypercalcemia
Decreases serum phosphorus and calcium concentrations
Decreased ECV effect on Ca renal regulation
+ sympathetics –> Na reabsorption in PCT
Ca reabsorption depends on transepithelial voltage and solvent drag, which depend on Na reabsorption
What are the major regulatory factors for renal handling of phosphate
FGF23 - increases excretion
PTH - increases excretion
Vit D3 - increases serum Pi by increasing intestinal absorption
Insulin - lowers serum levels by shifting into cells
How is Pi reabsorbed in the PT
Across apical membrane via Na/Pi symporters
Across basolateral membrane via unknown transporter
What effect does PTH have on Pi excretion
PTH inhibits Na/Pi transporters and Na/H antiporter in apical membrane of PT cells, thus increasing excretion
What effect does acidosis vs. alkalosis have on Pi excretion?
Chronic acidosis increases Pi excretion
Chronic alkalosis decreases Pi excretion
Magnesium reabsorption pathways
PT: 20%, paracellular, follows Na and H2O
TAL: 70%, paracellular, depends on uptake of Na and K via NKCC2 and lumen positive voltage of TAL
DCT: 10%, fine-tuning, electric potential = primary driver, crosses apical border via TRPM6, no known mechanism for shuttling or crossing basolateral membrane
What effect do diuretics have on Mg reabsorption
Decrease reabsorption
