1.3.2 Tubular Reabsorption Flashcards
Where are amino acids reabsorbed?
The proximal tubule.
What are the functional characteristics of the ascending loop of henle?
Moderate trans-cellular and para-cellular permeability
Reabsorbs 25% of salt
Reabsorbs NaCl and Mg
What are the functional properties of the proximal tubules?
High trans-cellular permeability to H2O and salt
High paracellular ion and H2O conduction
Absorbs 100% of glucose and amino acids
Secretes uric acid and drugs
High reabsorption rate/low gradient
What establishes the electrochemical gradient in the basolateral membrane?
The combination of the Na-K-ATPase and K channels establish the gradient at -80mV
If there were no other channels in the apical membrane, the whole cell would be at -80mV
What provides the tight junctions in the renal tubular epithelium?
zonula occludens
How do the apical and basolateral surfaces of the renal tubular epithelium differ?
Transport mechanisms, channels and receptors are different.
What are the two ways that substances can pass through the renal tubular epithelium?
The transcellular pathway
The paracellular pathway - between cells across the Zona Occludens
How does the proximal tubule compare to the collecting duct in regards to water reabsorption?
In the proximal tubule - it relies on the hydrostatic pressure vs the oncotic pressure
In the collecting duct - ADH regulates the amount of aquaporins that are on the membrane surface
What is the important apical membrane channel in the collecting tubule?
Sodium is reabsorbed from the tubular lumen through Na+ channels in the apical membrane (the ENaC, epithelial Na+ channel)
How can an SGLT-2 inhibitor be used to treat diabetes? (Kidney mascot slide)
Gliflozins are a type of drugs that inhibit glucose in the renal tubules by blocking the SGLT2 ttransporter, which is responsible for more than 90% of glucose reabsorption of the kidney. They are used to treat type II diabetes mellitus; they cause glucosuria and lower blood glucose levels. They have a series of other secondary effects, such as loss of body weight, blood pressure, diuretic effect due to the osmotic action of glucose and dehydration, urinary infections due to the high glucose content of the urine.
What are the functional characteristics of the collecting tubules?
Low para and trans cellular permeability to H2O and ions
Secretion of H+ and HCO3-
Variable NaCl reabsorption depending on aldosterone
Variable H2O reabsorption depending on ADH
What is the important glucose channel in the proximal tubule?
The SGLT-2 channel
How does the apical membrane differ from the basolateral membrane?
The presence of other transporters in the apical membrane modify the gradient. So if there is a sodium channel there would be a depolarization of the apical membrane at -30mV
What are the functional characteristics of distal tubules?
Low trans and para cellular permeability
Reabsorption of NaCl
Reabsorption and secretion of K+
Variable reabsorption of NaCl depending on aldosterone
Variable reabsorption of H2O depending on ADH
Inhibition of the Na/K ATPase in the proximal tubule will have what effect?
inhibition of the Na,K-ATPase in the proximal tubule will disrupt the Na gradient and impair secretion of H. Also, it will diminish glucose and water reabsorption and will depolarize the epithelium.
What is the important apical membrane channel in the thick ascending loop of henle?
Na+-K+-2Cl- cotransporter
What is glomerulotubular balance?
Variations in GFR could produce substantial changes in the amount of filtered sodium and alter the Na+ balance. This does not occur because tubular Na+ reabsorption is adjusted to the sodium filtered load.
This phenomenon, designated glomerulotubular balance (GTB) (note that it is not the same as glomerulotubular feedback), through which sodium and water reabsorption parallels the changes in GFR and the amount of filtered Na+. The proportion of Na+ and water reabsorbed in the proximal tubule is always the same regardless the total volume of filtrate.
Two factors have to be considered in the GTB:
- Oncotic and hydrostatic pressures difference between peritubular capillaries and intercellular space. When GFR increases, if the renal plasma flow is maintained, the plasma protein concentration in the glomerular capillaries rises and, of course, it is also increased in the peritubular capillaries, thus increasing net water and solute reabsorption by the proximal tubule.
- The increment of GFR increases the amount of glucose and amino acids filtered in the glomeruli. As reabsorption of these solutes is coupled to that of Na+ in the symporters of the proximal tubules, Na+ and water reabsorption follows the variations in filtered glucose and amino acids.
What is the important apical membrane channel in the distal tubule?
In the early segment of the tubule, Na+ and Cl- are reabsorbed via a Na+-Cl- symporter in the apical membrane.
Explain the mechanism of bicarbonate reabsorption in the proximal tubule.
Note the Na+-H+ antiporter.
Bicarbonate reabsorption in proximal tubules
The proximal tubule reabsorbs approximately 90% of the filtered bicarbonate. This activity is coupled to the secretion of protons by the Na+-H+ antiport in the apical membrane. In the tubular lumen, bicarbonate (HCO3-) takes a proton and forms carbonic acid (H2CO3). TheThe enzyme carbonic anhydrase, present in the brush border, catalyzes the reaction H2CO3 ⇒H2O + CO2. CO2 diffuses freely into the cell through the apical membrane. Within the cell there is also carbonic anhydrase that catalyzes the reverse reaction of hydration of CO2 to reform carbonic acid. This dissociates into H+ and HCO3-; the protons are sent to the lumen by the Na+-H+ exchanger and bicarbonate is transferred to the interstitium by the 3HCO3- : 1 Na+ symport in the basolateral membrane. This transport is driven primarily by the electrical gradient.
The whole process causes disappearance of one HCO3- from the tubular fluid while another bicarbonate is transferred from the cell to the peritubular capillaries. The final result is the same as if HCO3- would be transported as such across the cell.
Bicarbonate is reabsorbed at a faster rate than Cl- in the initial segment of the tubule.
Explain how magnesium reabsorption occurs in the loop of henle.
Most of the reabsorption of Mg2+ (~60%) occurs in the thick ascending limb of Henle’s loop. The transfer to the interstitial space is mainly passive via the paracellular route, driven by the transtubular electrical gradient (lumen positive). A small proportion of Mg2+ is also reabsorbed transcellularly. Entry through the apical membrane is favored by the high electrochemical gradient and probably involves Mg2+ channels. Active transport systems in the basolateral membrane (Mg2+-ATPase and Na+-Mg2+ exchanger) move Mg2+ to the interstitium. Reabsorption of Mg2+ in the distal tubules and collecting ducts is very poor.
Discuss the reabsorption profile for major solutes along the nephron.
Understand that the majority of Mg reabsorption is done in the ascending Loop on Henle
Explain the mechanism of Cl- reabsorption in the proximal tubule.
Chloride reabsorption in proximal tubules
Chloride is reabsorbed actively via a transcellular pathway and passively via the paracellular pathway.
The transcellular pathway requires an exchanger in the luminal membrane that operates in association with the Na+-H+ antiport. Chloride in the luminal fluid is exchanged for other intracellular anion, for example formate (H.COO-). Although formate is in low concentration in the cell, it is recycled across the apical membrane and can maintain continuous operation of the antiport. Formate is transferred to the lumen in exchange for Cl-. In the lumen, formate is titrated by protons secreted by the Na+-H+ antiport. Formic acid is the protonated, uncharged product, and can diffuse freely into the cell, where it dissociates to formate and H+. Both are recycled back to the lumen by the Cl–formate and Na+-H+ exchangers respectively. It is obvious that Cl- reabsorption depends on the operation of the Na+,K+-ATPase, that maintains a low intracellular Na+ concentration and drives the Na+-H+ antiport.
Reabsorbed chloride returns to the circulation through Cl- channels and K+-Cl- symports in the basolateral membrane, both driven by the negative potential within the cell.
The initial rise in chloride concentration in the luminal fluid of the early segment of the tubule establishes a chemical gradient for Cl- passive diffusion through the paracellular pathway.
How does tubuloglomerular feedback compare to glomerulotubular balance?
Other than tight junctions, what are some other junctional complexes of renal epithelial cells?
Adhering junction
Desmosome
Gap junction
Hemi-desmosome
What are the major apical membrane channels in the proximal tubule?
The Na-glucose symporter
Na-H antiporter
Explain glucose handling by the kidney. (Kidney mascot slide)
Glucose reabsorption
The capacity of proximal tubules to reabsorb glucose is limited. The maximum amount of any substance that can be reabsorbed is called tubular maximum (Tm). The Tm for glucose is approximately 375 mg/min. When the load of filtered glucose exceeds this amount, glucose is excreted in urine.
Assuming a glycemia of 100 mg/dL, with a GFR of 125 mL/min, the glucose filtered will be 125 mL/min ´ 1 mg/mL = 125 mg/min, well below the Tm. Theoretically, excretion of glucosein urine (glucosuria) should appear when glucose concentration exceeds 300 mg/dL (125 mL/min ´ 3 mg/mL = 375 mg/ml = Tm). However, glucosuria is already observed in patients with a glycemia of 180 mg/dL. The plasma concentration at which glucose first appears in urine is the so-called renal plasma threshold for glucose.
That apparent deviation from the Tm is called splay and has been explained by differences in reabsorbing efficiency among nephrons. Some of the nephrons will spill glucose in the urine at lower glucose loads than expected from the Tm value for all the kidney.
Glucosuria is a common symptom in uncontrolled diabetes mellitus patients with hyperglycemia. It is also found in cases with normal glycemia and defects of glucose reabsorption in the proximal tubules (renal glucosuria).
