Renal Handling of Salt and Water: Part 1
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Questions and Answers

What characteristic of the glomerular filtrate is most critical for the kidneys to regulate the volume and composition of bodily fluids?

  • It contains a higher concentration of plasma proteins than blood.
  • It is devoid of any cellular components.
  • It has a significantly lower osmotic pressure than blood plasma.
  • Its composition is nearly identical to plasma, excluding larger proteins and cells. (correct)

In tubular epithelial cells, what role do tight junctions play in the absorption and secretion processes?

  • They directly regulate the activity of ATPase pumps.
  • They maintain functional polarity by restricting protein movement between apical and basolateral sides. (correct)
  • They facilitate the transport of large proteins across the cellular membrane.
  • They actively secrete ions against their electrochemical gradient.

Which factor most directly facilitates the movement of water across tubular epithelial cell membranes?

  • The presence of tight junctions preventing paracellular water movement
  • Active transport of electrolytes creating an osmotic gradient (correct)
  • Direct energy expenditure by aquaporins
  • Hydrostatic pressure differences between the filtrate and the interstitium

A patient's urine sample shows a high glucose concentration despite normal blood glucose levels. Which transporter dysfunction is the LEAST likely cause?

<p>Overexpression of aquaporins in the collecting duct (A)</p> Signup and view all the answers

How does the kidney ensure nearly all filtered protein is reabsorbed under normal physiological conditions?

<p>Proteins bind to megalin and cubulin receptors, are endocytosed, and degraded within lysosomes. (D)</p> Signup and view all the answers

A patient has increased protein in their urine due to tubular damage. What factor is LEAST likely to contribute to this condition?

<p>Increased basolateral transport of proteins into the interstitium (B)</p> Signup and view all the answers

What is the primary mechanism by which amino acids are reabsorbed in the proximal convoluted tubule?

<p>Secondary active transport coupled to sodium (D)</p> Signup and view all the answers

Why is the reabsorption of bicarbonate in the proximal convoluted tubule essential for acid-base homeostasis?

<p>It prevents the excretion of filtered bicarbonate, conserving the body's buffering capacity. (C)</p> Signup and view all the answers

A drug that inhibits carbonic anhydrase in the proximal convoluted tubule would MOST directly impair:

<p>Bicarbonate reabsorption (D)</p> Signup and view all the answers

What role do organic ion transporters in the proximal convoluted tubule play in maintaining homeostasis?

<p>They facilitate the removal of potentially toxic organic compounds. (C)</p> Signup and view all the answers

What is the significance of the countercurrent mechanism in the Loop of Henle for urine concentration?

<p>It creates a hypertonic medullary interstitium. (A)</p> Signup and view all the answers

Which segment of the nephron is LEAST permeable to water, contributing to the dilution of the filtrate?

<p>Thick ascending limb of the Loop of Henle (C)</p> Signup and view all the answers

How do loop diuretics like furosemide affect kidney function by disrupting salt reabsorption?

<p>By blocking the Na+/K+/2Cl- cotransporter (NKCC2) in the thick ascending limb. (D)</p> Signup and view all the answers

What is the primary function of the early distal convoluted tubule in regulating fluid and electrolyte balance?

<p>Reabsorbing sodium chloride via thiazide-sensitive cotransporters (D)</p> Signup and view all the answers

How does aldosterone influence sodium reabsorption and potassium secretion in the late distal convoluted tubule and collecting duct?

<p>By increasing ENaC expression, enhancing sodium reabsorption and potassium secretion (C)</p> Signup and view all the answers

What is the primary role of ADH (Vasopressin) in the late distal convoluted tubule and collecting duct regarding urine concentration?

<p>It increases water permeability by upregulating aquaporins. (B)</p> Signup and view all the answers

How do intercalated cells in the late distal convoluted tubule and collecting duct contribute to acid-base balance?

<p>By reabsorbing bicarbonate and secreting hydrogen ions (B)</p> Signup and view all the answers

Which combination of factors listed MOST directly results in hyperkalemia?

<p>Decreased aldosterone activity, acidosis (C)</p> Signup and view all the answers

Which statement best describes the differences in solute handling between the proximal tubule and the collecting duct?

<p>The proximal tubule reabsorbs a constant fraction; the collecting duct’s electrolyte transport is hormonally regulated. (B)</p> Signup and view all the answers

A patient with uncontrolled diabetes mellitus has persistently high blood glucose levels. How does this MOST directly affect urine production and composition?

<p>It saturates SGLT2 transporters, causing osmotic diuresis and glucose excretion. (A)</p> Signup and view all the answers

In which condition is the primary defect in the proximal tubule?

<p>Fanconi syndrome (A)</p> Signup and view all the answers

What is the primary location where tubular fluid osmolarity can increase to 1200 mOsm/L?

<p>The medullary interstitium near the bottom of the loop of Henle (D)</p> Signup and view all the answers

Which of the following best describes the physiological response to a severe drop in blood pressure concerning renal handling of salt and water?

<p>Increased ADH secretion to promote water reabsorption (B)</p> Signup and view all the answers

Why does altering the permeability of the distal tubules and collecting ducts affect the final urine volume and concentration?

<p>These segments play a leading role in directly impacting the final composition of urine. (A)</p> Signup and view all the answers

How does damage to the glomerulus affect urine composition?

<p>Results in increased protein excretion (D)</p> Signup and view all the answers

If the Na+/K+ ATPase pump is inhibited throughout the nephron, what result would likely occur?

<p>Reduction in the production of concentrated urine (C)</p> Signup and view all the answers

Which best characterizes glomerulotubular balance?

<p>Proportionate increase of reabsorption in proximal tubule to increase of glomerular filtration rate (A)</p> Signup and view all the answers

If a person ingested a drug that decreased the afferent arteriole radius of the glomerulus, how would that MOST directly affect filtrate volume with all else held constant?

<p>Filtrate volume would initially decrease (C)</p> Signup and view all the answers

A mutation that causes over-expression of the Na+/K+/2Cl synporter symporter (NKCC2) in the loop of Henle would result in all of the following EXCEPT:

<p>Increased potassium loss (D)</p> Signup and view all the answers

What is the most likely outcome in urine electrolyte composition when a patient takes a drug that has a similar function to vasopressin?

<p>Decreased sodium and chloride (D)</p> Signup and view all the answers

Which action related to kidney filtration is most likely to occur during a sympathetic 'fight-or-flight' response in the body?

<p>Afferent artieroles constrict (C)</p> Signup and view all the answers

A competitive inhibitor medication is designed to block aldosterone receptors in the late distal tubule and collecting ducts. What is the anticipated effect on final urine composition?

<p>Potassium retention while increased sodium excretion (C)</p> Signup and view all the answers

Which of the following characterizes the function of the thin ascending limb in the loop of Henle regarding urine concentration?

<p>Diluting the urine (A)</p> Signup and view all the answers

How do ACE inhibitors lead to lower blood pressure?

<p>Decreasing aldosterone release (A)</p> Signup and view all the answers

How are proteins reabsorbed for use within the body?

<p>Large vesicles engulf the protein, catabolize it into smaller amino acids, that are functional within the body, and then are pushed into the interstitial fluid (C)</p> Signup and view all the answers

What direct effect occurs on the medullary concentration gradient when vasopressin secretion is chronically impaired?

<p>The concentration gradient of sodium chloride does not move as much (A)</p> Signup and view all the answers

An investigator who discovers a new drug that blocks aquaporin channels in the late distal tubule and the collecting duct would expect to see which of the following?

<p>Diluted urine is produced (D)</p> Signup and view all the answers

A patient showing edema is prescribed a loop diuretic which acts on the ascending loop of Henle. What changes can be recorded in urine analysis after the medication?

<p>Significant increase in the concentrations of Na+, K+, and Cl- (C)</p> Signup and view all the answers

A newly developed drug blocks the reabsorption of urea in the medullary collecting duct. How will this medication impact a normal person's urine?

<p>Diluted urine (B)</p> Signup and view all the answers

Blocking reabsorption of sodium chloride impacts reabsorption of water through which mechanism?

<p>Creating of an osmotic gradient (A)</p> Signup and view all the answers

Which cellular adaptation would most likely be observed for proximal convoluted tubule cells?

<p>Increased microvilli (C)</p> Signup and view all the answers

Why can kidney damage cause anemia?

<p>Kidney synthesizes and uses the hormone erythropoietin that is stimulated by hypoxia; damaged kidney cannot facilitate this (A)</p> Signup and view all the answers

A mutation disrupts the function of the Na+/K+ ATPase pump specifically in the basolateral membrane of the proximal convoluted tubule cells. What is the MOST likely direct consequence?

<p>Reduced water reabsorption due to decreased osmotic gradient (B)</p> Signup and view all the answers

A researcher is studying a novel drug that selectively targets aquaporins in the nephron. If the drug completely blocks aquaporin-1 channels, which of the following would be the MOST direct expected outcome?

<p>Substantial reduction in water reabsorption in the proximal tubule and descending limb of the loop of Henle (C)</p> Signup and view all the answers

A patient with a genetic disorder exhibits a significantly reduced number of functional Na+-H+ exchangers (NHEs) in the apical membrane of the proximal tubule cells. Which of the following compensatory mechanisms is LEAST likely to occur in response to this defect?

<p>Upregulation of apical membrane aquaporins to maintain water balance (D)</p> Signup and view all the answers

In a clinical study, researchers are investigating the effects of a drug that inhibits carbonic anhydrase specifically within the tubular lumen. Which of the following changes in urine composition and electrolyte balance would MOST likely be observed?

<p>Elevated excretion of bicarbonate ions in the urine (A)</p> Signup and view all the answers

A novel toxin selectively impairs the function of the Na+/K+/2Cl- cotransporter (NKCC2) in the thick ascending limb of the loop of Henle. Predict the MOST direct effect on urine concentration and volume.

<p>Decreased urine osmolarity and increased urine volume (B)</p> Signup and view all the answers

What distinguishes tubular secretion from reabsorption in the nephron?

<p>Secretion transports solutes from peritubular capillaries into the tubular lumen, while reabsorption transports solutes from the tubular lumen into the blood. (C)</p> Signup and view all the answers

How do tubular epithelial cells contribute to urine formation?

<p>By reabsorbing water, ions and nutrients, and secreting waste and excess substances. (C)</p> Signup and view all the answers

How does the Na+/K+ ATPase pump in the basolateral membrane of tubular cells contribute to transepithelial solute transport?

<p>It maintains a low intracellular Na+ concentration, facilitating Na+ entry across the apical membrane. (D)</p> Signup and view all the answers

A drug that inhibits the Na+/H+ exchanger (NHE) in the proximal tubule would directly affect the reabsorption of which substance?

<p>Bicarbonate (A)</p> Signup and view all the answers

A patient is diagnosed with Fanconi syndrome. Considering the functions of the proximal tubule, which set of abnormalities would be MOST expected in their urine?

<p>Increased glucose, amino acids, and bicarbonate. (B)</p> Signup and view all the answers

Why does the osmolarity significantly increase as the filtrate flows down the descending limb of the Loop of Henle?

<p>Water is reabsorbed into the medullary interstitium due to the high osmolarity. (D)</p> Signup and view all the answers

What is the direct effect of the Na+/K+/2Cl- cotransporter (NKCC2) in the thick ascending limb of the loop of Henle on the medullary interstitium?

<p>It increases the osmolarity of the medullary interstitium. (D)</p> Signup and view all the answers

In the distal convoluted tubule (DCT), what effect does parathyroid hormone (PTH) have on calcium reabsorption?

<p>PTH promotes calcium reabsorption in the DCT (A)</p> Signup and view all the answers

A patient presents with a condition that causes decreased aldosterone secretion. What changes in electrolyte balance and blood pressure would you expect to observe?

<p>Decreased sodium reabsorption, increased potassium concentration, and decreased blood pressure. (A)</p> Signup and view all the answers

What is the primary mechanism by which ADH increases water reabsorption in the collecting duct?

<p>By increasing the number of aquaporin-2 channels in the apical membrane. (A)</p> Signup and view all the answers

How do intercalated cells in the collecting duct respond to a decrease in blood pH?

<p>By secreting hydrogen ions and reabsorbing bicarbonate ions. (B)</p> Signup and view all the answers

What is the effect of increased plasma protein concentration on glomerular filtration?

<p>Glomerular filtration rate may decrease. (D)</p> Signup and view all the answers

What is the effect on urine production if a drug blocks aquaporin channels in the collecting duct?

<p>Increased urine volume and decreased osmolarity. (A)</p> Signup and view all the answers

Damage to the glomerulus most directly affects urine composition how?

<p>Increasing protein concentration in the filtrate. (A)</p> Signup and view all the answers

How is urea reabsorbed for use within the body?

<p>It is transported across the tubular epithelium via a urea transporter. (D)</p> Signup and view all the answers

What is the main advantage of countercurrent multiplication?

<p>It establishes a high medullary concentration. (C)</p> Signup and view all the answers

What transport mechanism is primarily responsible for glucose reabsorption in the proximal tubule?

<p>Secondary active transport (A)</p> Signup and view all the answers

What effect will a drug that increases afferent arteriolar resistance and efferent arteriolar resistance have on glomerular filtration rate (GFR)?

<p>Cannot be determined (D)</p> Signup and view all the answers

Which transport mechanism is primarily involved in the reabsorption of amino acids in the proximal tubule?

<p>Secondary active transport (C)</p> Signup and view all the answers

How does increased hydrostatic pressure affect the filtration rate?

<p>The filtration rate will increase due to higher net filtration pressure (C)</p> Signup and view all the answers

How does the kidney contribute to anemia?

<p>By inhibiting erythropoietin (C)</p> Signup and view all the answers

What would be a result of decreasing the radius of both the efferent and afferent arterioles?

<p>Decrease in filtration rate (B)</p> Signup and view all the answers

If the amount of Na/K ATPase pumps increase on the basolateral membrane, which event would occur?

<p>Increase in active transport of sodium (D)</p> Signup and view all the answers

If the thick ascending limb is impermeable to water and permeable to ions, then:

<p>The osmolarity of the filtrate in this area decreases (B)</p> Signup and view all the answers

How osmolarity in filtrate change as it enter the loop of Henle and then enter the ascending loop of Henle?

<p>Osmolarity increases then decreases (B)</p> Signup and view all the answers

What describes best the role of Type A intercalated cells?

<p>They secrete H+ and reabsorb bicarbonate (B)</p> Signup and view all the answers

What describes how the kidney regulate blood pressure?

<p>By secretion the right amount of fluid to maintain blood volume (B)</p> Signup and view all the answers

How would an ACE inhibitor medication work to lower hypertension?

<p>Inhibiting the production of angiotensin II (A)</p> Signup and view all the answers

The reabsorption of water occurs where?

<p>Proximal tubule and descending loop of Henle (C)</p> Signup and view all the answers

Damage to what area impacts ability to concentrate urine?

<p>Collecting duct and loop of Henle (B)</p> Signup and view all the answers

What will characterize the function of the thin ascending limb in the loop of Henle with regard to urine concentration?

<p>Passive reabsorption of sodium increases concentration of urine (B)</p> Signup and view all the answers

What is the main function of tight junctions?

<p>Preventing paracellular movement (C)</p> Signup and view all the answers

What is the main function of Aquaporin-1?

<p>Mediating water reabsorption (C)</p> Signup and view all the answers

What is the primary result from inhibiting carbonic anhydrase?

<p>Inhibited reabsorption of bicarbonate (C)</p> Signup and view all the answers

Overactivity of the Na+/K+/2Cl- cotransporter (NKCC2), will result in what effect?

<p>Excessive potassium being excreted (A)</p> Signup and view all the answers

Why is it important to reabsorb bicarbonate?

<p>For acid-base hemostasis (D)</p> Signup and view all the answers

Which mechanism helps maintain low [Na+]i?

<p>Na/K APTase pump (D)</p> Signup and view all the answers

What section in the tubule has cuboidal epithelial cells?

<p>Proximal convoluted tubule (D)</p> Signup and view all the answers

In the proximal convoluted tubule (PCT), a drug that inhibits the Na+/H+ exchangers (NHEs) on the apical membrane would MOST directly affect the reabsorption of which of the following substances?

<p>Bicarbonate, due to the reduced secretion of H+ required for its reabsorption. (C)</p> Signup and view all the answers

A patient is prescribed a medication that inhibits the Na+/K+/2Cl- cotransporter (NKCC2) in the thick ascending limb of the loop of Henle. What is the MOST likely effect on the osmolality of the medullary interstitium?

<p>Decrease in osmolality, as the reduced reabsorption of ions impairs the establishment of the medullary gradient. (B)</p> Signup and view all the answers

If a person's body is undergoing an acidotic state, how would the intercalated cells in the collecting duct respond to help restore blood pH?

<p>Increase the reabsorption of bicarbonate ions and secrete hydrogen ions into the tubular fluid. (A)</p> Signup and view all the answers

A researcher discovers a mutation that selectively impairs the function of aquaporin-1 channels in the proximal tubule. Predict the MOST direct effect on the nephron's handling of water and overall urine output.

<p>Decreased obligatory water reabsorption in the proximal tubule and increased urine volume. (C)</p> Signup and view all the answers

A previously healthy individual begins taking a new medication that inhibits aldosterone release from the adrenal cortex. How would their kidneys MOST likely respond to maintain electrolyte balance and blood pressure?

<p>Decreased sodium reabsorption and increased potassium reabsorption in the distal tubule and collecting duct, leading to natriuresis and potassium retention. (D)</p> Signup and view all the answers

Flashcards

What is glomerular filtrate?

Fluid in the Bowman's capsule of the renal corpuscle.

What are tubular reabsorption and secretion?

Reabsorption removes substances from the tubular fluid; secretion adds substances.

What is tubular reabsorption?

The process by which solutes and water are removed from the tubular fluid and transported into the blood.

What is tubular secretion?

The transport of solutes from peritubular capillaries into the tubular lumen.

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What is passive secretion?

Using channels or carriers, substances move down concentration gradients.

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What is active secretion?

The movement of molecules against gradients, using energy-dependent ATPase pumps.

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What is functional polarity?

The ability of epithelial cells to express different transport proteins on their apical and basolateral sides to enable vectorial transport of solutes.

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What are epithelial transport proteins?

Specialized proteins embedded in epithelial cell membranes that form transport pathways.

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What is the primary function of Na+/K+ ATPase pump?

Maintains a low intracellular sodium concentration, driving transepithelial solute transport.

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What are ion channels?

Pores selective for certain ions, gated and opened in response to specific stimuli.

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How does transport occur with ion channels?

Transport through these proteins occurs passively along electrochemical gradients.

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What are carriers?

Proteins that co-transport (symporters) or exchange (antiporters) substances across membranes.

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What is the function of aquaporins?

Transport solute-free water across cell membranes along osmotic gradients. Can transport bi-directionally.

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How is urine formed?

Urine is formed by processing glomerular filtrate.

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What does the proximal convoluted tubule reabsorb?

The early proximal convoluted tubule reabsorbs many filtered solutes like NaCl, ions, glucose, and amino acids.

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How does uptake occur in the PCT?

Uptake here occurs primarily through sodium (Na+) nutrient cotransporters.

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What happens in early proximal tubule?

Glucose reabsorption which is proportionate to the amount filtered until a transport maximum is reached.

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What is SGLT-2?

It is a Na/Nutrient cotransporter that primarily facilitates the sodium/glucose co-transport.

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What is glycosuria?

Occurs when the filtered load of glucose exceeds the tubular maximum for reabsorption.

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What is filtered in Glomerulus?

Hormones and albumin are filtered

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What is filtered in the glomerulus?

Low MW proteins, ionic charge and molecular shape

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What is proteinuria?

the urinary loss of proteins due to increased glomerular permeability, tubular reabsorption dysfunction, or increased protein plasma concentrations.

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What occurs in Fanconi Syndrome?

This causes loss of amino acids, protein, glucose and bicarbonate in the urine

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What are the permeability characteristics of the thin descending limb of the Loop of Henle?

The thin descending limb has low permeability to ions and solutes and is highly permeable to water.

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What are the permeability characteristics of the thin ascending limb of the Loop of Henle?

The thin ascending limb is impermeable to water, but passively permeable to ions.

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Loop of Henle actively reabsorbs?

This actively reabsorbs Na+ and Cl- from the filtrate through the NKCC2 cotransporter, diluting the filtrate and concentrating

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How do loop diuretics work?

They inhibit the NKCC2 cotransporter in the thick ascending limb

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What is the DCT important for?

NaCl transport in the early distal tubule

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What happens in DCT?

Na+ enters through NCC. Inhibited by Thiazide diuretics

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What occurs late Distal Convoluted Tubule/Collecting Ducts?

Na+ is reabsorbed through ENaC. Electrogenic Na+ reabsorption creates a negative charge in the lumen and is under control of aldosterone

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What does aldosterone do?

These are a key hormone regulating blood pressure and influence salt reabsorption

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What do K-sparing diuretics do?

Act by inhibiting ENaC or aldosterone

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High potassium intake result in ?

Increased aldosterone = Increased ENaC.

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What do late DCT/CD do?

These regulate urea absorption

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What occurs in intercalated cells in the late DCT and CD?

Unlike proximal convoluted tubule, it is a non-volatile acid secreted in the DCT/CD

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Kidney's primary function?

The kidneys regulate the volume and composition of bodily fluids by forming urine.

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What plasma components are filtered?

All plasma components are filtered, except larger plasma proteins and cells, that form the glomerular filtrate.

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How do the tubules alter the glomerular filtrate?

Reabsorption is removing substance from filtrate and secretion is adding substance to filtrate.

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What may tubular epithelial cell do?

These cells can remove/reabsorb substances from filtrate or secrete/add substances to filtrate.

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How does filtrate osmolarity change?

Filtrate osmolarity changes dramatically throughout the nephron, from 300 mOsm/L to 1200 mOsm/L and back.

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What is the PCT epithelium?

Cuboidal epithelium with microvilli and lots of mitochondria.

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What is passive diffusion?

Solutes are absorbed through epithelial cells following concentration gradients.

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What is active transport?

Establishes concentration gradients, using energy derived from Na+/K+ ATPase pumps

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How does water cross tubular epithelial cells?

Water crosses membranes through tight junctions/paracellular space and via aquaporins.

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What are tight juctions?

They form homotypic bonds with neighboring cells; permeable to water, ions, and small molecules.

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How is water transported in kidneys?

Osmotic gradients drive passive water transport to/from the filtrate.

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Name other segments of nephron?

Loop of Henle, distal convoluted tubule, and collecting duct.

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What happens if filtered AA levels are elevated?

70% reabsorbed, the rest of the proximal tubule becomes involved.

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What transporters are for organic ions?

Multiple drug resistance protein (MDR1); p-glycoprotein, organic acid transporters (OATs), organic cation transporters (OCTs) etc

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What is bulk reabsorption?

Isotonic reabsorption of solutes and water

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What is the main job of angiotensin II?

Increases NaCl reabsorption in the proximal tubule.

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What does ANP do?

Causes decreased NaCl reabsorption in the collecting duct

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What does ADH do?

Increases H20 reabsorption in collecting duct

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What is Loop of Henle Function?

Maintenance of a highly concentrated medullary interstitium

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What is the thick ascending limbs Role

Creates a lumen +ve charge that drives cation absorption

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Study Notes

  • The lecture discusses the renal handling of salt and water in the formation of urine - part 1.
  • The learning objectives include understanding glomerular filtrate composition, fluid and electrolyte transport, and urine composition.
  • Also covered are the roles of different renal tubule segments and the mechanisms of reabsorption and secretion.
  • Course: Renal System Module
  • Code: MED 204
  • Lecturer: Dr. Stephen Keely & Dr. Patrick Walsh
  • Date: February 2025

Primary Kidney Function

  • Kidneys regulate the volume and composition of bodily fluids.
  • This is achieved through the formation of urine.

Glomerular Filtration

  • Glomerular filtrate is the fluid in the Bowman's capsule lumen within the renal corpuscle.
  • The formation rate is 115-125 ml/min, approximately 180L per day.
  • Filtration occurs from blood through the glomerulus capillaries and Bowman's capsule podocytes.
  • Filtration is driven by blood pressure, and all plasma components are filtered except large proteins and cells.

Renal Tubule Structure and Function

  • The primary function of renal tubules in urine formation transforms glomerular filtrate.
  • Tubular epithelial cells facilitate reabsorption which removes substances from the filtrate.
  • Tubular epithelial cells also secrete, adding substances to the filtrate.
  • Changes in filtrate osmolarity along the tubules drive water movement and urine formation.

Tubular Reabsorption

  • Reabsorption is the process where solutes and water are moved from the tubular fluid back into the blood.
  • Reabsorbed substances include electrolytes, glucose, proteins, amino acids, and urea.
  • This process maintains homeostasis of blood volume, pressure, pH, and osmolarity.
  • Solute absorption uses specific transport proteins arranged into pathways.
  • Passive diffusion absorbs solutes through epithelial cells along concentration gradients.
  • Active transport establishes concentration gradients using energy from Na+/K+ ATPase pumps.
  • Filtrate osmolarity changes along the nephron:
    • PCT: 300 mOsm/L which is the same as plasma
    • Descending LoH: increases to 1200 mOsm/L as water is reabsorbed
    • DCT & CD: osmolarity varies with permeability

Tubular Secretion

  • Tubular secretion moves solutes from peritubular capillaries or interstitium into the tubular lumen.
  • Secretion clears substances from the blood, unlike reabsorption which retains them.
  • Secreted substances include waste/unwanted products like K+, H+, NH4+, creatinine, urea, hormones and drugs.
  • Urea secretion into the tubular fluid contributes to urine formation.
  • Secretion of H+ and NH4 is important for maintaining blood pH.
  • Secretion uses similar processes to reabsorption, but in reverse.
  • Passive secretion is the diffusion of molecules along osmotic or chemical gradients.
  • Active secretion moves molecules against gradients using energy-dependent ATPase pumps.

Tubular Epithelial Cells

  • Tubular epithelial cells differ along the nephron's length, depending on function.
  • PCT cells are cuboidal epithelium which increase surface area for reabsorption which is supported by their rich mitochondria, which are needed for efficient reabsorption via active transport.
  • In Loop of Henle "thick" and "thin" refer to cell size.
    • Thin limbs are squamous.
    • Thick limbs are cuboidal.
  • Two common properties of these cells facilitate absorption and secretion:
    • tight junctions
    • functional polarity

Tight Junctions

  • Tight junctions are a point of contact between neighbouring cells.
  • They consists of transmembrane proteins that form homotypic bonds with neighboring cells.
  • Tight junctions are permeable to water, ions, and small molecules, forming a paracellular pathway.
  • Structural components of tight junctions include occludins, claudins, and junctional adhesion molecules (JAM).
  • They are closely associated with intracellular signalling and cytoskeletal proteins, controling permeability.

Functional Polarity

  • Functional polarity in epithelial cells refers to their ability to express different transport proteins on apical and basolateral sides.
  • This configuration enables vectorial transport of solutes.

Epithelial Transport Proteins

  • Specialized proteins in epithelial cell membranes form pathways that enable water-soluble molecules to cross hydrophobic cell membranes.
  • The 3 main types are:
  • ATPase pumps
  • Channels
  • Carriers: co-transporters and exchangers

Na/K ATPase Pump

  • The Na/K ATPase pump helps to drive the transport of tubular fluid and electrolytes.
  • Its primary function is to maintain a low intracellular sodium concentration.
  • This drives transepithelial solute transport.

Ion Channels

  • Ion channels act as selective pores for certain ions.
  • Their opening is gated and stimuli-responsive.
  • Transport occurs passively along electrochemical gradients established by ATPase pumps.

Carriers

  • Two types of carriers are present on renal tubules:
    • Co-transporters (symporters)
    • Exchangers (antiporters)
  • Transport proteins arrange into specific pathways that facilitate the movement of solutes to and from filtrate across membranes.
  • Water follows by osmosis.

Water Movement

  • Water crosses cell membranes through tight junctions and paracellular space or via water channels called aquaporins.
  • Aquaporins are expressed along tubules and is bidirectional
  • Aquaporins transport solute-free water across membranes along prevailing gradients from active solute transport.
  • Different Aquaporins occur in different regions regulated by antidiuretic hormone (ADH):
  • Aquaporin-1 is abundant in proximal tubule and descending thin limb, mediating H₂O reabsorption.
  • Aquaporins 3 and 4 occur in DCT and collecting ducts, and water reabsorption.

Summary

  • The kidneys form urine by processing glomerular filtrate.
  • Tubular absorption and secretion are controlled by epithelial cells.
  • Water transport is passive and follows osmotic gradients.
  • Osmotic gradients use transepithelial solute transport.
  • Solute transport occurs using specific transport proteins on apical and basolateral cell surfaces, and include:
    • ATPase pumps
    • Ion Channels
    • Carriers: cotransporters (symporters), and exchangers (antiporters)

Volume and Osmolarity

  • In corpuscle filtration volume is 180L and osmolarity is 300 mOsm/L with a pH of 7.4.
  • Tubule reabsorption and secretion yields a volume of 1.5L and osmolarity of 500-850 mOsm/L with a pH of 6.5

Proximal Convoluted Tubule (PCT) Function

  • Early in the PCT many filtered solutes are reabsorbed as well as NaCl, ions, glucose, amino acids, phosphate, lactate, citrate, and urea.
  • Uptake uses Na+/Nutrient Cotransporters (CT) with types for glucose, Pi, amino acids, and lactate.
  • By the time filtrate exits the PCT, 100% of both glucose and amino acids are reabsorbed.
  • Also reabsorbed are 70% sodium, 70% potassium, 90% bicarbonate, 85% phosphate, 50% urea, lactate, and citrate.
  • The PCT also reabsorbed 70% passively of filtered water (about 130 L).

PCT - NaCl Reabsorption Mechanics

  • The PCT is important in net sodium reabsorption
  • The glomerular filtration rate is 26,000 mM Na daily, only 150 mM is excreted.
  • Around 95.5% of filtered Na is reabsorbed, about 70% of this occurs in the PCT
  • The basolateral Na+/K+ ATPase pump drives sodium reabsorption.
  • Sodium absorption also works to maintains an electrochemical gradient across membrane
  • Sodium enters the early PCT enters via apical Na+/solute co-transporters and Na+/H+ exchangers (NHEs).
  • The early PCT is relatively Cl- impermeable.
  • Cl - concentrations increase in the filtrate
  • The late PCT's Cl- is reabsorbed passively through the paracellular pathway.

PCT - Glucose Reabsorption

  • Glucose is reabsorbed in the early portion of the PCT.
  • The amount reabsorbed is proportionate to filtered amount but this is limited by transporter maximum rate (TmG = 2 mmol/min).
  • Glucose undergoes secondary active transport using gradient derived from basal Na/K ATPase activity for reabsorption.
  • Uptake occurs through Na+/Nutrient cotransporter which primarily sodium/glucose co-transporter, SGLT-2 and SGLT-1.
    • Basolateral Na/K ATPase pumps Na+ out in exchange for K+ which crosses the apical membrane through SGLT2.
    • The transport drags in cotransport of Na+ along a Glucose carrier (GLUT 2).
    • Sodium exits into interstitium through the original pump together with glucose.
  • Since the same action moves glucose in same direction its a symporter - and this is the traget Gliflozins.

Glycosuria

  • Almost all the glucose in the PCT is reabsorbed.
  • Tmg is only 3 times higher than the normal filtered lead, increases in filtered load may lead to glucose being excrted = glycosuria.
  • Glycosuria is detectable by a simple dipstick test
  • Elevated plamsa glucose causes a high glucose called hyperglycaemia which is indicative of Diabetes mellitus (Type 1 or 2). Both Type 1 or 2 are characterized by persistently high blood glucose levels - and causes diuersis.
  • Normal plamsa glucose can be present in hypoglycaemia die to redcued tubular reapsorptive acpaity, or renal blood flow.

PCT Protein

  • Protein reabsorption is dpeendent on molecular size, smaller size makes it easier to get filtered.
  • Lower sized proteins are eaier to be reabsorbed.
  • Elevated plasma levels fo a protein lead to inrased filtation.

Protein repasobtion by PCT

  • Filtered proteins bind to recports.
  • bound proteins undergo endocytosis and fuse to form lysosomes.
  • lysosome proteases degrade proteins with resultant exit of amino acids.

Proteinuria

  • An increased amount of protien in the uring and is diagnosed as foam and/or by a dipstick test .
  • Can be from damage or a high protien load or dysfunction.

Amino Acids

  • Amino acids (AA) can derive from 3 sources
    • glomerular filtration
    • enzymatic degradation eg hormoens
    • diffusion
  • 80% of AAs are reabsorbed in the first PCT
  • the are absorbed by N+ in the first third.

Loop of Henle's Role

  • The three functions are Thin Descending Limb, and Thin Ascending Limb, and Thick Ascending Limb
  • The function is maintaneac highly concentrated in the medulla while driving water absoprtion from the tuble
  • Osmolart is affected with most found iin the coretx

Salt Reapsorption

Loop Of Hinle

Loop Diuretics

  • Act by inhibiting NKCC2 in the thick ascending limb of the loop of Henle
  • Inhibit salt reabsorption more potently than most other diuretics
  • can be increased several times over - referred to as “high ceiling diuretics”.

Distal Convoluted tubule

  • Approximately 80% of the filtered water has been recovered by end of the loop, with 36L entering the DCT and with with another 10-15% being recovered here
  • This segment 5 mm long and has two types:
    • Early - no water
    • Late - water, aduretric formol

Late Distal Convoluted tubule + Collecting Duct

  • 2 epethilal with primciapll cell with transports
  • K secretion increases significantly in the late
  • DCT/CD in parallel with ENaC expression

Distal CONVULATED TUBULE + CLOOECTING DUCTS

  • *80% of the bdyt's k is traceullular, lofe threatening!
  • high potassium
  • low potssioum!
  • potassium secretion

Distal Convoluted Collecting:

Combines to fine tune depending on water

Summary

  • Most of the golemrular filtrati is Reabsorbed in the pct!
  • 20% of h20 and 25% of ions

Summary

  • The kidneys form urine by processing glomerular filtrate.
  • Tubular absorption and secretion are controlled by epithelial cells.
  • Water transport is passive and follows osmotic gradients.
    • Osmotic gradients uses transepithelial solute transport. .

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Description

Explore the renal handling of salt and water in urine formation. Understand glomerular filtrate composition and the functions of renal tubules. Learn about fluid and electrolyte transport, reabsorption, and secretion mechanisms.

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