HRR: renal tubule I and II Flashcards
What are the two big methods of transport across the tubule?
Transcellularly or paracellularly
What allows passive transport to be possible in the tubule?
Concentration gradient established by the sodium potassium pump
Describe the importance of the sodium potassium pump in the tubule.
It transports sodium from the interior of the cell through the basolateral membrane, creating negative intracellular potential that creates a favorable gradient for sodium entry for reabsorption.
What helps create different permeabilities to water in different parts of the tubule?
The presence/structure of the tight junctions and aquaporins in a given area.
Where is most solute reabsorption happening?
The proximal tubule
What is the segment of the tubule controlled by hormones?
The collecting duct
What are the main solutes reabsorbed in the proximal tubule?
Sodium, chloride, bicarb, phosphate, glucose
What is secreted by the proximal tubule?
Acids, bases, and hydrogen ions into the tubular lumen
Proximal tubule reabsorption is ___tonic with plasma.
Isotonic
What provides energy for reclamation in the proximal tubule?
The electrochemical gradient from the sodium potassium pump
What is solvent drag?
Passive paracellular reabsorption of solute and water due to leaky tight junctions of the proximal tubule. It results from a greater tonicity in the interstitial fluid compared to luminal fluid.
How is bicarb reabsorbed in the proximal tubule?
The sodium-proton exchanger
Describe the sodium-proton exchanger in relation to movement of bicarb.
- Filtrate enters the proximal tubule.
- Sodium-proton exchanger on the apical membrane brings sodium into the cell and puts proton into the lumen of the tubule.
- Proton in the tubule combines with bicarb to form carbonic acid, which converts to CO2 and water.
- CO2 diffuses into the epithelial cell, where it recombines with water to form carbonic acid.
- Carbonic acid dissociates into bicarb and a proton.
- Proton is exchanged for sodium via NHE3, and the bicarb is transported into the interstitial space.
How can declining kidney function lead to drug toxicity?
Usually, the kidneys secrete drugs and toxins through the tubular cells and into the lumen to clear them from the blood. When kidney function declines, they can’t clear these substances which can lead to toxicity.
Where does a lot of phosphate get reabsorbed?
The proximal tubule
Where is glucose reabsorbed?
The proximal tubule via SGLT
How much glucose should be in the urine?
Usually none, unless SGLT is saturated via issues with the transporter.
What is the thin descending limb of the loop of Henle permeable to?
Highly permeable to water, not super permeable to solute.
What happens to the concentration of urine as it travels down the thin descending limb?
It becomes more concentrated due to water moving out.
What is the thick ascending limb permeable to?
Salt and chlorine, but not water.
Where is there no reabsorption of water?
The thick ascending limb of the loop of Henle.
What is significant about the reabsorption of salt in the thick ascending limb of the loop of Henle?
It contributes to generating the hypertonic medullary interstitium, which is a pulling force for water later on!
What is the main drive for reabsorption of NaCl in the thick ascending limb?
The Na/K/Cl transporter (NKCC2)
Describe the role of potassium in the thick ascending limb of the loop of Henle.
Potassium becomes high in the cells and leaks back into the tubule via ROMK. This creates a positive charge in the lumen that drives paracellular reclamation of cations like calcium and magnesium.
How does the loop of Henle help generate the hypertonic medullary interstitium?
- NaCl reabsorption. 2. Urea recycling. 3. Countercurrent exchange in the medulla.
The macula densa is in the…
Distal convoluted tubule
What is the main transport protein active in the distal convoluted tubule?
The NaCl cotransporter NCC
What is the target of thiazide diuretics?
NCC
What is reabsorbed in the distal convoluted tubule?
Sodium and chloride, but not water!
What keeps sodium concentration of distal convoluted tubule cells low?
Sodium potassium pump
How does chloride get out of the distal tubule cells?
Diffuses into the interstitial fluid via chloride channels
What part of the nephron is a target for PTH to reabsorb calcium?
Distal convoluted tubule
What composes the cortical collecting duct?
Principal cells, alpha-intercalated cells, and beta-intercalated cells
What do principal cells do?
Reabsorb sodium and potassium
What do alpha-intercalated cells do?
Secrete hydrogen and reabsorb bicarb and potassium
What do beta-intercalated cells do?
Secrete bicarb and reabsorb H+ as needed
How is sodium reabsorbed in the collecting duct?
ENaC in principal cells
What is significant about sodium reabsorption in the collecting duct?
It creates a negative luminal potential
Why can diuretics lead to hypokalemia?
They cause more sodium in the collecting ducts, which will increase the amount of sodium leaving the ducts via ENaC and create an even larger negative potential that pulls potassium in.
What controls sodium reabsorption in the collecting duct?
Aldosterone increasing the sodium potassium pump and ENaC activity in principal cells. This helps us hold onto salt and water and waste potassium.
Where does ADH act?
The collecting duct
How does ADH work in the collecting ducts?
It stimulates insertion of aquaporin 2 channels on the luminal side of principal cells, allowing for reabsorption of water back into the blood.
What happens to principal cells in the absence of ADH?
They become essentially impermeable to water; this helps us control the dilution or concentration of urine.
What plays a major role in acidifying urine?
Alpha-intercalated cells via excretion of protons.
What happens with protons and bicarb in alpha intercalated cells?
H+ is secreted and combines with bicarb to form carbonic acid. The carbonic acid converts back to CO2 and water. These then diffuse into the alpha-intercalated cells and recombine to form carbonic acid that then splits back into bicarb and a proton. The proton will follow the previous cycle, and the bicarb enters the blood.
What happens with protons and bicarb in beta-intercalated cells?
CO2 and water combine to form carbonic acid, which splits to form a proton and bicarb. The proton enters the blood, and the bicarb enters the urine. Helps us dump bicarb during alkalosis.
What is the final site for processing urine?
Medullary collecting ducts
What controls the permeability of the medullary collecting duct to water?
ADH
What part of the nephron is a site for ANP and BNP regulation?
Medullary collecting ducts
What do naturetic peptides do in the collecting duct?
Inhibit insertion of aquaporins to reduce water reabsorption and reduce sodium-potassium pump activity to block Na+ reabsorption. This helps lower blood volume.
What do naturetic peptides do to GFR?
Increase it via dilation of afferent arteriole.
What part of the nephron is permeable to urea?
The medullary collecting ducts
Describe Bartter syndrome.
Loss of function mutation in TAL channels, mostly NKCC2, results in hypokalemic salt-wasting.
Describe Gitelman syndrome.
Loss of function mutation in NCC channel in the DCT. Causes an increase in serum calcium, high plasma renin, low extracellular fluid, secondary hyperaldosteronism, hypokalemia, and metabolic alkalosis.
What is Liddle syndrome?
Hypokalemic salt retaining tubulopathy that results from a gain of function mutation in ENaC in the cortical collecting duct. It resembles hyperaldosteronism.
