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Questions and Answers
Which segment of the nephron is responsible for developing urine with variable osmolality and solute composition?
Which segment of the nephron is responsible for developing urine with variable osmolality and solute composition?
What is the main reason why the thin descending limb is highly permeable to water?
What is the main reason why the thin descending limb is highly permeable to water?
Which structure is primarily responsible for reabsorption of NaCl in the thick ascending limb?
Which structure is primarily responsible for reabsorption of NaCl in the thick ascending limb?
What is the net effect of fluid movement as it progresses through Henle's loop?
What is the net effect of fluid movement as it progresses through Henle's loop?
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In which part of the nephron does reabsorption of Ca primarily occur through paracellular transport?
In which part of the nephron does reabsorption of Ca primarily occur through paracellular transport?
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What drives the reabsorption of Mg and Ca across epithelia paracellularly in the thick ascending limb?
What drives the reabsorption of Mg and Ca across epithelia paracellularly in the thick ascending limb?
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Which isoform of aquaporin is specific to the Henle's loop and is activated by phosphorylation?
Which isoform of aquaporin is specific to the Henle's loop and is activated by phosphorylation?
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What modification can increase Ca reabsorption in the distal tubule?
What modification can increase Ca reabsorption in the distal tubule?
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Which segment of the nephron is responsible for diluting urine even more?
Which segment of the nephron is responsible for diluting urine even more?
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What drives the reabsorption of Na and Cl into the cell by the Na/Cl cotransporter in the distal tubule?
What drives the reabsorption of Na and Cl into the cell by the Na/Cl cotransporter in the distal tubule?
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What dictates the flow of ions across the nephron epithelium?
What dictates the flow of ions across the nephron epithelium?
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Which segment of the nephron is responsible for almost all organic substrate reabsorption?
Which segment of the nephron is responsible for almost all organic substrate reabsorption?
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Which mechanism is responsible for reabsorption of solutes from urine into kidney cells?
Which mechanism is responsible for reabsorption of solutes from urine into kidney cells?
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What causes the lumenal pH to drop in the late proximal tubule?
What causes the lumenal pH to drop in the late proximal tubule?
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What is the primary mechanism by which water is reabsorbed into capillaries from kidney cells?
What is the primary mechanism by which water is reabsorbed into capillaries from kidney cells?
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What happens to uric acid primarily in the liver?
What happens to uric acid primarily in the liver?
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Which transporter is responsible for both reabsorption and secretion of uric acid in the proximal tubule?
Which transporter is responsible for both reabsorption and secretion of uric acid in the proximal tubule?
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What is the role of carbonic anhydrase in the nephron?
What is the role of carbonic anhydrase in the nephron?
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What is the primary energy source required for the active transport of most solutes across the nephron epithelium?
What is the primary energy source required for the active transport of most solutes across the nephron epithelium?
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In the nephron, what dictates the flow of water across epithelial cells?
In the nephron, what dictates the flow of water across epithelial cells?
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Which transport process in the nephron is coupled to the reabsorption of organic substrates?
Which transport process in the nephron is coupled to the reabsorption of organic substrates?
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What enzyme is involved in breaking down carbonic acid into water and carbon dioxide in the nephron?
What enzyme is involved in breaking down carbonic acid into water and carbon dioxide in the nephron?
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What is the net effect of the late proximal tubule's transport activity regarding ion reabsorption?
What is the net effect of the late proximal tubule's transport activity regarding ion reabsorption?
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In the nephron, what is primarily responsible for moving chloride ions through the paracellular route?
In the nephron, what is primarily responsible for moving chloride ions through the paracellular route?
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Which mechanism leads to the reabsorption of solutes from urine into kidney cells in the nephron?
Which mechanism leads to the reabsorption of solutes from urine into kidney cells in the nephron?
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Which segment of the nephron is responsible for developing urine with variable osmolality and solute composition?
Which segment of the nephron is responsible for developing urine with variable osmolality and solute composition?
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What is the primary driving force for osmotic water flow from the tubular fluid into the interstitium in the thin descending limb of Henle's loop?
What is the primary driving force for osmotic water flow from the tubular fluid into the interstitium in the thin descending limb of Henle's loop?
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What is the primary function of the thick ascending limb of Henle's loop?
What is the primary function of the thick ascending limb of Henle's loop?
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Which aquaporin isoform is known to be abundant in the collecting duct and can be modified in its expression?
Which aquaporin isoform is known to be abundant in the collecting duct and can be modified in its expression?
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What is the role of Na/K/2Cl cotransporter in the thick ascending limb of Henle's loop?
What is the role of Na/K/2Cl cotransporter in the thick ascending limb of Henle's loop?
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What is the net effect of transport in the distal tubule?
What is the net effect of transport in the distal tubule?
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What drives Mg and Ca across epithelia paracellularly in the thick ascending limb?
What drives Mg and Ca across epithelia paracellularly in the thick ascending limb?
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Where are AQP3 and AQP4 primarily located within the nephron?
Where are AQP3 and AQP4 primarily located within the nephron?
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What is primarily responsible for generating the high osmolality of the interstitial fluid in the medulla?
What is primarily responsible for generating the high osmolality of the interstitial fluid in the medulla?
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What is a distinctive characteristic of epithelial cells in the thin descending limb that contributes to their function?
What is a distinctive characteristic of epithelial cells in the thin descending limb that contributes to their function?
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What is the primary function of vasopressin receptor antagonists?
What is the primary function of vasopressin receptor antagonists?
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Which hormone modulates water reabsorption in the collecting tubules?
Which hormone modulates water reabsorption in the collecting tubules?
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What is the primary criteria for osmotic diuretics based on the text?
What is the primary criteria for osmotic diuretics based on the text?
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What is the main action of vasopressin V2 receptor activation?
What is the main action of vasopressin V2 receptor activation?
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Which of the following best describes the effect of vasopressin on water channels?
Which of the following best describes the effect of vasopressin on water channels?
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What is the consequence of using V2 receptor antagonists on AQP2 translocation?
What is the consequence of using V2 receptor antagonists on AQP2 translocation?
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How do osmotic diuretics limit water reabsorption in the nephron?
How do osmotic diuretics limit water reabsorption in the nephron?
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What is the primary objective of vasopressin/ADH hormone in collecting tubules?
What is the primary objective of vasopressin/ADH hormone in collecting tubules?
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Which enzyme is activated by vasopressin to facilitate transcellular H2O transport?
Which enzyme is activated by vasopressin to facilitate transcellular H2O transport?
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What is the primary effect of vasopressin V2 receptor antagonists on AQP2 translocation?
What is the primary effect of vasopressin V2 receptor antagonists on AQP2 translocation?
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What is the primary mechanism by which loop diuretics such as furosemide and bumetanide work?
What is the primary mechanism by which loop diuretics such as furosemide and bumetanide work?
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How do carbonic anhydrase inhibitors, as diuretics, affect urine pH and cells?
How do carbonic anhydrase inhibitors, as diuretics, affect urine pH and cells?
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Which diuretic is a direct descendant of thiazide diuretics?
Which diuretic is a direct descendant of thiazide diuretics?
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What is the primary effect of thiazide diuretics on ion transport in the nephron?
What is the primary effect of thiazide diuretics on ion transport in the nephron?
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What is the main mechanism of action of potassium-sparing diuretics like spironolactone?
What is the main mechanism of action of potassium-sparing diuretics like spironolactone?
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Which transporter do thiazide diuretics specifically inhibit in the nephron?
Which transporter do thiazide diuretics specifically inhibit in the nephron?
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Study Notes
Proximal Tubule
- Bulk absorber of the nephron
- Concentration of tubular fluid beyond the proximal tubule remains relatively unchanged
- Reabsorption and secretion of various solutes occur in the proximal tubule
Loop of Henle
- Reabsorption of NaCl, K, Ca, and Mg occurs in the loop of Henle
- Tubular fluid becomes dilute (hypotonic) compared to plasma and interstitium
- The interstitial fluid of the medulla is extremely hypertonic, with osmolality reaching up to 1200 mOsm/kg H2O
- Half of the osmolality is due to NaCl and the other half due to urea
- The thin descending limb of the loop of Henle is very permeable to water due to the presence of aquaporin channels
Aquaporin Family
- More than 200 aquaporin (AQP) isoforms have been identified across species
- At least 7 AQP isoforms are known to be present in the human kidney
- AQP1 is a tetrameric complex of 4 identical monomers and is abundant in the proximal tubule and thin descending limb
- AQP2 is abundant in the collecting duct and its expression can be modified by vasopressin
- AQP3 and AQP4 are located on the basolateral membrane in the collecting duct
Thin Descending Limb
- Initially, the fluid in the thin descending limb is isosmotic compared to the interstitium
- An osmotic pressure gradient develops as the fluid moves through the loop, resulting in osmotic water flow from the tubular fluid into the interstitium
- The tubular fluid becomes very concentrated, reaching up to 1200 mOsm/kg H2O
Thin and Thick Ascending Limb
- The ascending portion of Henle's loop is impermeable to H2O but permeable to some solutes (Na, Cl, and K)
- The ascending limb is referred to as the diluting segment
- Fluid entering the ascending limb has a higher NaCl concentration than the interstitium due to the concentrating actions of the descending limb
- Passive diffusion of Na and Cl occurs, and H2O cannot follow
- In the thick ascending limb, Na, Cl, and K are further reabsorbed, and H2O cannot follow
Na/K/2Cl Cotransporter
- Na, Cl, and K are transported into cells by a downhill gradient
- Energy comes from the electrochemical potential gradient generated by NaK ATPase on the basolateral membrane
- 1Na:2Cl:1K = electroneutral
- Cl leaves cells on the basolateral side through Cl channels and KCl co-transporter via electrochemical gradient
- K can leave cells on the basolateral side through the KCl co-transporter
- K can also leak from the cell on the apical side through K channels, resulting in a lumen-positive electrical potential
- Lumen-positive electrical potential drives Mg and Ca across epithelia paracellularly
Distal Tubule
- Na and Cl continue to be reabsorbed in the distal tubule
- Ca is also reabsorbed (transcellular) in the distal tubule
- Like the thick ascending limb, the distal tubule epithelium is relatively impermeable to H2O
- The distal tubule dilutes the urine even more
Collecting Tubule
- The collecting tubule is responsible for the final modification of the urine
- The collecting tubule is responsible for the reabsorption and secretion of various solutes
Nephron
- The nephron is the functional unit of the kidney
- Each kidney has approximately 10^6 nephrons
- The nephron is divided into four sections: proximal tubule, loop of Henle, distal tubule, and collecting tubule
- The nephron begins at the glomerulus and ends at the ureter
- The length of the nephron spans the renal cortex and medulla
Nephron Epithelium
- The nephron is lined with a single layer of epithelial cells
- Epithelial cells have apical (lumen) and basolateral (interstitial) sides
- Different types of epithelial cells line the nephron segments
- Ionic and water flow are dictated by the properties of these epithelial cells
Movement across the Nephron Epithelium
- Na dictates ionic flow, and water follows
- Active Na reabsorption occurs throughout the nephron
- The NaK ATPase is located on the basolateral membrane throughout the nephron
- The NaK ATPase pumps 3 Na ions out to the interstitium for every 2 K ions into the cell
- The NaK ATPase creates an electrochemical potential gradient
- The energy required for transport of most other solutes comes from the ECP gradient generated by the NaK ATPase
Reabsorption of Organic Substrates
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Na is more abundant outside of the cell (interstitium and lumen)
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The ECP favors Na entry from the lumen into the cell
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It is inefficient to waste energy from the ECP
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Therefore, active transport of organics is coupled to Na reabsorption; NaS cotransporters
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Almost all organic substrates are reabsorbed in the proximal tubule
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However, there are a finite number of transporters in each cell
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Transport maximum is attained when all nephrons are reabsorbing at maximum rate### Proximal Tubule
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Proximal tubule is a bulk absorber
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Concentration of tubular fluid beyond proximal tubule remains relatively unchanged
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Nephron beyond the proximal tubule is specialized to develop urine with variable osmolality and solute composition
Reabsorption and Secretion in the Loop of Henle
- Net effect: reabsorption of NaCl, K reabsorption, Ca and Mg reabsorption (paracellular)
- Tubular fluid becomes dilute (hypotonic compared to plasma and interstitium)
Transport in the Thin Descending Limb
- Interstitial fluid of the medulla is extremely hypertonic in comparison to plasma
- Osmolality can rise to as high as 1200 mOsm/kg H2O
- ½ of osmolality is due to NaCl and ½ due to urea
- Epithelial cells of thin descending limb are very thin (hence the name) and lack significant amounts of mitochondria (no energy source)
- No active transport processes for solutes
- However, they are very permeable to water due to specialized channels called aquaporins
The Aquaporin Family of H2O Channels
- More than 200 aquaporin (AQP) isoforms identified across species
- At least 7 are known to be present in human kidney
- AQP monomers consist of 6 transmembrane domains
- AQP1 is a tetrameric complex of 4 identical monomers
- AQP1 is abundant in the proximal tubule and thin descending limb, its expression is relatively consistent
- AQP2 is abundant in collecting duct, its expression can be modified; the principal target of vasopressin
Transport in the Thin and Thick Ascending Limb
- Initially, the fluid in the thin descending limb is isosmotic (equal) compared to the interstitium
- However, an osmotic pressure gradient develops as fluid moves through the loop
- Results in osmotic water flow from tubular fluid into the interstitium (H2O gets reabsorbed)
- Tubular fluid becomes very concentrated (1200 mOsm/kg H2O)
- At the loop’s bend, the tubular fluid enters the thin ascending limb
- The ascending portion of Henle’s loop is impermeable to H2O but permeable to some solutes: primarily Na, Cl, and K
- Ascending limb is referred to as diluting segment
- Fluid entering the ascending limb has higher (NaCl) than interstitium from concentrating actions of descending limb
- Passive diffusion of Na and Cl (paracellular)
- H2O cannot follow
- Fluid then enters the thick portion of the ascending limb
- Epithelial cells are thicker in this region and contain numerous mitochondria
- Na, Cl, and K are further reabsorbed in the thick ascending limb
- H2O cannot follow
The Na/K/2Cl Cotransporter of the Thick Ascending Limb
- Na, Cl, and K are transported into cells by a downhill gradient
- Energy comes from ECP generated by NaK ATPase on the basolateral membrane
- 1Na:2Cl:1K = electroneutral
- Cl leaves cells on the basolateral side through Cl channels and KCl cotransporter via electrochemical gradient
- Likewise, K can leave cells on the basolateral side through the K-Cl cotransporter
- K can also leak from the cell on the apical side through K channels; resulting in lumen-positive electrical potential
- Lumen-positive electrical potential drives Mg and Ca across epithelia paracellularly
Distal Tubule and Collecting Tubule
- Na and Cl continue to be reabsorbed in the distal tubule
- Ca is also reabsorbed (transcellular)
- Like the thick ascending limb, distal tubule epithelium is relatively impermeable to H2O
- Dilutes urine even more
- Na and Cl transported into cells by Na/Cl cotransporter
- Energy comes from the ECP gradient from basolateral NaK ATPase
- Ca actively transported into the cell by the Ca channel and across the basolateral membrane by the Na/Ca exchanger
- Ca reabsorption can be modified by parathyroid hormone (PTH) at this point
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Description
Test your knowledge on the functions and segments of the nephron, including the Proximal Tubule, Loop of Henle, Distal Tubule, and Collecting Tubule. Learn about the epithelium lining the nephron and its different types of epithelial cells.
