Control of Reabsorption and secretion in the nephron Flashcards
What is the usual GFR rate?
125 ml/min
What hormone can particularly change GFR?
Angiotensin 2
What substances are almost completely reabsorbed and have virtually no trace in urine, also absorbed in the proximal tubule?
Glucose and amino acids
What is the function of the sodium potassium pump?
- Transports sodium from the interior of thr across the basolateral membrane creating a low intracellular electrical potential
- This causes sodium to diffuse from the tubular lumen into epithelial cells through brush border
What is the intracellular potential inside tubular epithelial cells?
-70 mV
What is the charge in the tubular lumen in the proximal tubule?
-3 mV
Explain secondary active transport?
As one of the substances diffuses down its electrochemical gradient (e.g sodium) the energy released is used to drive another substance (e.g glucose) against its electrochemical gradient
What do elcetrolytes pass through when they move paracellularly?
Leaky tight junctions
What does Na+/K+ATPase cause?
- Intracellularly low concentrations of sodium and high concentrations of K+
- Creates concentration gradients which can be used to drag other ions either into the cell or out of the cell
What causes Na+ to diffuse from the tubular lumen into the epithelial cells through the brush border?
- Na+/K+ATPase creating a low intracellular Na+ concentration and negative intracellular electrical potetential through Na/K+ATPase transporting Na+ from the interior of the cell across the basolateral membrane
What is the negative intracellular electrical potential mostly due to?
Potassium efflux (potassium channels not Na+/K+ATPase pump)
Why is the tubular lumen slightly more negative (3mV) than the interstitial fluid?
On apical surface of tubular cells there are many transporters that transport sodium into the cell as well as a non-charged solute (e.g glucose)
How is glucose taken up?
- SGLT2 (secondary active transport) 1 Na+ per glucose
- SGLT1 (takes 2 Na+ for every 1 glucose)
SGLT1 more distal in proximal tubule
What mechansim does the NHE-Na/H exchanger use?
Counter-transport (used to pump sodium out of the cells)
What percentage of sodium and water is reabsorbed in the proximal tubule?
65%
What is secreted into the tubule from the tubular cells?
H+, organic acids, bases (mostly in the distal part)
Where is glucose uptaken?
100% in proximal tubule
What percentage of filtered water is reabsorbed in the loop of Henle?
20%
What percentage of filtered sodium, chloride and potassium is reabsorbed in the loop of Henle?
25%
Where is the majority of Magnesium absorbed?
Thick ascending limb (~80%) (paracellularly driven by positive luminal chrage)
What is the potential in the tubular umen in the loop of Henle?
+8mV
What is the main transporter in the thick ascending limb?
NKCC2
What percentage of sodium is absorbed in the distal tubule?
5%
What are the 2 main cells in the late section of the distal tubule?
- Principal cells
- Intercalated cells
How are Ca++ and Mg++ uptaken in the distal tubule?
Specific transporters
What do principal cells absorb?
- Na+ Cl-
- H2O if ADH is present
What do alpha intercalated cells do in the distal tubule?
- Absorb K+
- Secrete H+
What do principal cells excrete?
K+
What do Beta intercalated cells excrete?
HCO3-
What is the potential of the tubular lumen in the early distal tubule?
-10mV
What is the transporter which is affected by thiazide diuretcics in the distal tubule?
Na+/Cl- symporter
Where are principal cells found?
- Cortical collecting tubule
- Late distal tubule
What cells are sensitive to aldosterone?
Principal cells
What channel alows na+ to pass from the lumen into the cell?
ENaC (Na+ the gets pumped out of Na+/K+ATPase into interstitium)
What does the regulation of sodium cholride result in the excretion of?
K+
How is Cl- often uptaken in the collecting tubule?
Paracellularly
What is the main purpose of alpha-intercalated cells?
Secrete acid
What are beta-intercalated cells involved in mostly?
Absorbing protons or excreting bicarbonate
What percentage of filtered water and sodium ions are absorbed at the medullary collecting ducts?
less than 10%
Can the medullary collecting ducts absorb water?
Impermeable unless ADH is present
What does ADH allow for the absorbption of in the medullary collecting ducts?
Water and urea
How does the medullary collecting duct play a role in the acid/base balance?
Can secrete H+ ions into lumen
How is glucose taken up?
- SGLT2 (secondary active transport) 1 Na+ per glucose
- SGLT1 (takes 2 Na+ for every 1 glucose)
SGLT1 more distal in proximal tubule
What mechansim does the NHE-Na/H exchanger use?
Counter-transport (used to pump sodium out of the cells)
What percentage of sodium and water is reabsorbed in the proximal tubule?
65%
What is secreted into the tubule from the tubular cells?
H+, organic acids, bases (mostly in the distal part)
Where is glucose uptaken?
100% in proximal tubule
What percentage of filtered water is reabsorbed in the loop of Henle?
20%
What percentage of filtered sodium, chloride and potassium is reabsorbed in the loop of Henle?
25%
Where is the majority of Magnesium absorbed?
Thick ascending limb (~80%) (paracellularly driven by positive luminal chrage)
What is the potential in the tubular umen in the loop of Henle?
+8mV
What is the main transporter in the thick ascending limb?
NKCC2
What percentage of sodium is absorbed in the distal tubule?
5%
What are the 2 main cells in the late section of the distal tubule?
- Principal cells
- Intercalated cells
How are Ca++ and Mg++ uptaken in the distal tubule?
Specific transporters
What do principal cells absorb?
- Na+ Cl-
- H2O if ADH is present
What do alpha intercalated cells do in the distal tubule?
- Absorb K+
- Secrete H+
What do principal cells excrete?
K+
What do Beta intercalated cells excrete?
HCO3-
What is the potential of the tubular lumen in the early distal tubule?
-10mV
What is the transporter which is affected by thiazide diuretcics in the distal tubule?
Na+/Cl- symporter (brings both Na+ and Cl- in)
Where are principal cells found?
- Cortical collecting tubule
- Late distal tubule
What cells are sensitive to aldosterone?
Principal cells
What channel alows na+ to pass from the lumen into the cell?
ENaC (Na+ the gets pumped out of Na+/K+ATPase into interstitium)
What does the regulation of sodium cholride result in the excretion of?
K+
How is Cl- often uptaken in the collecting tubule?
Paracellularly
What is the main purpose of alpha-intercalated cells?
Remove protons into the lumen and recover bicarbonate
What are beta-intercalated cells involved in mostly?
Absorbing protons or excreting bicarbonate
What percentage of filtered water and sodium ions are absorbed at the medullary collecting ducts?
less than 10%
Can the medullary collecting ducts absorb water?
Impermeable unless ADH is present
What does ADH allow for the absorbption of in the medullary collecting ducts?
Water and urea
How does the medullary collecting duct play a role in the acid/base balance?
Can secrete H+ ions into lumen
Where does aldosterone act?
- Collecting tubule and duct
What are the effects of aldosterone?
- Increased absorption of: NaCl and H2O
- Also sodium uptake into blood through ENaC
- Increased secretion of K+
- Major affect on principal cells of the cortical collecting duct
- Stimulates Na+/K+/ATPase
- Increases Na+ permeability on luminal side of principle cell membrane
- Stimulates apically located H+-ATPase in intercalated cells resulting in proton secretion
Where does angiotensin 2 act?
- Proximal tubule
- Thick ascending loop of Henle
- Distal tubule
- Collecting tubule
What is the effect of angiotensin 2?
Increased absorption of:
- NaCL
- H2O
Increased H+ secretion
- Also constricts afferent and efferent arteriole (more efferent
- Increases GFR
- Blood flow to vasa recta decreases, increasing oncotic pressure
- Na+ pump on basolateral side of tubular epithelia and the Na+/H+ exchange on the luminal membrane especially in the proximal tubule
Where does ADH act?
Distal tubule/collecting tubule and duct
What is the effect of ADH?
- Increased H2O reabsorption and urea transporters
Where does Atrial natriuretic peptide act?
Distal tubule / collecting tubule and duct
What is the effect of Atrial natriuretic hormone?
Decreased NaCL reabsorption
What is the site of action of Parathyroid hormone?
- Proximal tubule
- Thick ascending loop of henle
- Distal tubule
What is the effect of Parathyroid hormone?
- Decreased PO4 reabsorption
- Increased Ca++ reabsorption
Where is aldosterone released?
Adrenal cortex
What is the potential of the tubular lumen in the late distal and cortical collecting ducts?
-50mV
What tranporter does Amiloride and triamterene block?
Na+ channel on tubular epithelium in late distal and cortical collecting ducts (principal cells)
Where can ang 2 receptors be found?
Both the basolateral and apical surface
How many amino acids is angiotensin 2?
8 amino acids (can perfuse)
What does an increase in intracellular calcium as a result of angiotensin cause?
- Activation of Na+/H+ exchanger on the apical surface
- Na/K+ ATPase
- Na+/3HCO-3 exchanger (1 Na+ for 3 HCO-3 molecules electrogenic)
What does ADH bind to and how does this work?
- Specific V2 receptors and through signal transduction mechanisms stimulate the movement of a vesicular associated intracellular water channel called aquaporin 2 to the apical (luminal) surface of the epithelial cells
- Reversible to allow control of water permeability of these distal sections of the tubule
Describe the signal transduction mechanism when ADH binds to its receptor?
- ADh binds to ADH receptor on basolateral membrane of principal cell
- Activates stimulatory G protein to activate adenylate cyclase
- This converts ATP to cAMP
- cAMP activates protein kinase A
- Protein kinase A phosphorylates a number of key regulatory proteins which cause the movement and fusion of preformed secretory vesicles containing aquaporin 2 incorporating them into apical membrane making them permeable to H2O
- Driven by high concentration of solutes in peritubular fluid/interstitium drves water uptake into vasa recta
How does sympathetic nervous system affect the renal system?
Decreases sodium and water excretion mainly by constricting renal arterioles and so decreasing GFR (decrease blood flow to vasa recta, so increasing medullary interstitial osmolality). Can also increase angiotensin II formation (renin release) to increase tubular reabsorption and so decrease excretion of Na+ and H2O