Ion Transport In Renal Physiology Flashcards
What have transporters got to do with renal medicine?
- Bicarbonate reabsorption in the proximal tubule - pH control
- Na+ reuptake by the kidney - control of blood pressure - hypertension (high blood pressure)
How does sodium reabsorption occur in the proximal tubule?
- sodium needs to be take out of the filtrate in the lumen through the proximal tubule cell and into the capillary.
1. Basis of the transport is the sodium pump on the side of the cell next to the capillary that drives sodium out of the proximal tubule cell and into the capillary.
2. This creates a gradient for sodium inwards into the cell from the filtrate in the lumen .
3. This is done by sodium moving down its concentration gradient into the cell by the NHE (sodium, hydrogen exchanger). Causing acidification of the filtrate in the lumen
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How is bicarbonate reabsorbed in addition to sodium in the proximal tubule?
- The acidification of the filtrate is important because as sodium is taken up it is releasing bicarbonate and the bicarbonate buffers the hydrogen ions, by binding to form carbonic acid.
- Carbonic anhydrase (apical surface of the proximal tubule) catalyses the conversion of carbonic acid to water and carbon dioxide.
- The car in dioxide and water can freely diffuse across the membrane into the proximal tubule and the intracellular carbonic acid converts it because to carbonic acid.
- The carbonic acid dissociate to form H+ and bicarbonate ions, the H+ is pumped out again via the NHE and the bicarbonate is pumped into the capillary by the anion exchanger and chloride is pumped into the cell.
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Why does the kidney reabsorb all the bicarbonate filtered into the proximal tubule.
- The main reason is to retain base for pH buffers
How is renal control of circulating Na+ concentration a first line of treatment for mild hypertension?
- Amiloride inhibits the Na+ reuptake by the proximal tubule. By inhibiting the action of the NHE.
- Na+ excreted, as they are osmolytes , water follows the Na+ (diuresis)
- Reduced Na+ re-entering the blood, reduced uptake of water, reduced blood volume and thereby reducing blood pressure.
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What else does Amiloride inhibition effect?
By inhibiting the NHE, the filtrate isn’t acidified and the bicarbonate cannot be converted to carbonic acid and the water and carbon dioxide and enter the cell and this might have an effect on the pH buffering .
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How is sodium reabsorbed in the Thick ascending limb?
- The sodium pump on the side of the cell facing the capillary creates a gradient for sodium.
- This allows for the uptake of sodium from the filtrate in the lumen into the cell by the sodium potassium 2 Chloride co-transport (NKCC2 - allows the electroneutral transport of 3 ions)
- Sodium is take into the cell down its concentration gradient and the extruded into the blood in the capillary by the sodium pump.
What are the other transporters found in the thick ascending limb and what are there functions?
- The cell needs to balance the potassium and chloride ions in the cell.
1. Potassium chloride transport on the cell on side of the capillary, that pumps chloride and potassium out of the cell into the capillary
2. Chloride channel that pumps chloride into the capillary
3. The ROMK channels voltage sensitive potassium Chanel which pumps potassium it if the cell into the filtrate.
What Inhibits the NKCC2 co transport in the thick ascending limb?
- Loop diuretics drugs
- similar to amilirode as the prevent/reduce the sodium ion re-uptake across the thick ascending limb
- Therefore antihypertensive
How is sodium reabsorbed in the distal convoluted tubule?
- NCCT (sodium chloride co transport) brings sodium and chloride into the cells from the filtrate in the lumen.
- The sodium pump creates a sodium gradient and extrudes sodium ions into the blood in the capillary.
- The chloride coming in by the NCCT is pumped into the capillary by the potassium chloride co transporter and chloride ion.
- Potassium pumped into the cell by the sodium pump is pumped back into the capillary by the potassium chloride co transport.
- The ENaC (epithelial sodium channel) is non voltage gated and allows sodium to enter into the cell from the filtrate down its electrochemical gradient, so it can be transported into the blood.
What inhibits the NCCT and the ENaC of the distal convoluted tubule?
- NCCT is inhibited by thiazides, another choice for first line treatment for mild hypertension.
- ENaC is inhibited by amiloride, another drug for hypertension
What are Organic anion transporters (OAT)?
- Poly-specific an ionic (negatively charged) substrate transporters
- 11 OAT family members
- expressed in many tissues including
Kidney, liver, brain, retina and placenta
What are the organic anions that (OA-) are transported by the organic anion transporters (OAT)?
- Natural substrates:
- Conjugated sex steroids
- Carnitine
- Butyrate etc - Common drugs:
- Antibiotics
- Antivirals
- Diuretics
- Nutrients (vitamins, flavonoids)
How do Organic anion transporters (OAT) work in the proximal tubule?
- OATs pick up ions from the blood and transport them into the kidney (lumen - filtrate).
- They do this in exchange for dicarboxylate ions (organic ions which have 2 carboxylate groups), which are brought up into the cell by dicarboxylate transport which is driven by the inwards sodium gradient into the cell.
- So the OAT pumps dicarboxylate into the capillary and pumps out organic anions out of the capillary and into the cell, so it can be pumped intro the lumen.
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What type of transporters are OAT’s?
- OAT’s e.g. OAT1,2 and 3 are tertiary active transporters as there activity is driven by secondary active transporters which are driven by primary active transporters.
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