kidney function II: control of osmolality Flashcards
What is osmolality?
Osmolality (mosm/kg) is a measure of water concentration. The higher the solution osmolality, the lower the water concentration.
What is osmolarity?
Osmolarity (mosm/l) is a measure of water concentration. The higher the solution osmolarity, the lower the water concentration.
In describing physiological fluids, how are osmolality and osmolarity used?
Osmolality and osmolarity can be used interchangeably when describing physiological fluids.
Why is osmolality generally preferred over osmolarity?
Osmolality is preferred because it is independent of temperature.
What 3 types of urine can the kidney generate?
The kidney can generate dilute urine, iso-tonic urine, or concentrated urine.
What is the normal osmolality range for plasma?
Plasma osmolality ranges from 285-295 mosm/kg.
What is the osmolality range for urine?
Urine osmolality ranges from 50-1400 mosm/kg.
When does urine become concentrated?
Urine becomes concentrated during water deprivation.
When does urine become dilute?
Urine becomes dilute during water loading.
What is the difference between osmolality and osmolarity?
Osmolality is measured in mosm/kg, while osmolarity is measured in mosm/l (e.g., plasma 285-295 mosm/l).
What is the main osmotically active solute in plasma?
Sodium (Na⁺) is the main osmotically active solute in plasma.
What is the normal plasma sodium concentration?
Plasma sodium concentration ranges from 135-145 mmol/l.
Where is sodium freely filtered in the kidney?
Sodium is freely filtered at the renal corpuscle.
How is the amount of sodium filtered calculated?
Plasma Na⁺ concentration (mmol/l) × GFR (l/min) = Amount filtered
Example: 140 × 0.125 = 17.5 mmoles/min
What is the total amount of sodium filtered per day?
25,200 mmoles/day, with the majority being reabsorbed
Why is sodium balance important?
Sodium balance is linked to blood pressure regulation.
Where does sodium reabsorption primarily take place in the nephron?
Sodium reabsorption occurs throughout the tubule via active transport.
What are the four main sites of sodium reabsorption in the nephron?
Proximal tubule
Thick ascending limb
Distal tubule
Collecting duct (principal cells)
What organelle is abundant in the cells responsible for sodium reabsorption?
Mitochondria, which provide ATP for active sodium transport.
Where does sodium reabsorption occur in the Loop of Henle?
Sodium reabsorption occurs in the thin ascending limb (passively) but not in the descending limb.
Is sodium reabsorbed in the descending limb of the Loop of Henle?
No, the descending limb is impermeable to sodium.
How does sodium move in the thin ascending limb of the Loop of Henle?
Sodium is passively reabsorbed in the thin ascending limb.
What percentage of the filtered NaCl load is reabsorbed in the proximal tubule?
65% of the filtered NaCl load is reabsorbed in the proximal tubule.
What is the function of the Na⁺/H⁺ exchanger (NHE3) in the proximal tubule?
The Na⁺/H⁺ exchanger (NHE3) exchanges Na⁺ into the epithelial cell while secreting H⁺ into the lumen to facilitate sodium reabsorption.
What is the role of the Na⁺:K⁺ ATPase pump in sodium reabsorption?
The Na⁺:K⁺ ATPase pump actively pumps 3 Na⁺ out of the epithelial cell into the interstitial fluid and brings in 2 K⁺, helping to maintain a sodium gradient for reabsorption.
What percentage of the filtered NaCl load is reabsorbed in the thick and thin ascending limb?
25% of the filtered NaCl load is reabsorbed in the ascending limb of the loop of Henle.
What is the role of the Na⁺:K⁺:2Cl⁻ cotransporter in the thick ascending limb?
The Na⁺:K⁺:2Cl⁻ cotransporter actively transports Na⁺, K⁺, and 2Cl⁻ into the epithelial cell from the lumen, aiding in sodium reabsorption.
What percentage of the filtered NaCl load is reabsorbed in the distal tubule
2-5% of the filtered NaCl load is reabsorbed in the distal tubule.
What is the function of the Na⁺:Cl⁻ cotransporter in the distal tubule?
The Na⁺:Cl⁻ cotransporter actively transports Na⁺ and Cl⁻ into the epithelial cell from the lumen, facilitating sodium reabsorption.
What are the two main cell types in the collecting duct?
Principal cells – responsible for Na⁺ transport.
Intercalated cells – involved in H⁺ transport (acid-base balance).
What percentage of the filtered NaCl load is reabsorbed in the collecting duct?
5% of the filtered NaCl load is reabsorbed in the collecting duct.
What is the function of the ENa⁺ channel in the collecting duct?
The ENa⁺ channel (Epithelial Sodium Channel) allows sodium ions to pass from the lumen into the principal cells, facilitating sodium reabsorption
What are the three main factors that water reabsorption depends on?
Osmosis
Sodium reabsorption
Tubule permeability
How is water reabsorption in the proximal tubule coupled to sodium reabsorption?
Sodium is actively transported from the tubular lumen into the interstitial fluid, creating an osmotic gradient that drives water reabsorption via osmosis.
What is the role of tight junctions in water reabsorption?
Tight junctions in the proximal tubule are highly water-permeable, allowing water to follow sodium reabsorption isotonically.
What specialized water channels are present in the proximal tubule?
Aquaporin-1 (AQP1) channels are expressed in the proximal tubule membrane, facilitating efficient water transport.
What is the key requirement for producing a concentrated urine with an osmolality >300 mosm/kg?
Separation of sodium (Na⁺) and water reabsorption.
What role does the renal medulla interstitial fluid play in urine concentration?
It must have a high osmolality to drive water reabsorption from the collecting duct via osmosis.
What is the direction of flow in Henle’s loop?
countercurrent
How does the reabsorption of salt and water differ in Henle’s loop?
Salt reabsorption: 25% of the filtered sodium is reabsorbed.
Water reabsorption: 10% of the filtered water is reabsorbed.
What is the main function of the descending limb of the Loop of Henle?
Water reabsorption via AQP1 (aquaporin-1) channels.
Does the descending limb of the Loop of Henle reabsorb sodium?
No, sodium is not reabsorbed in the descending limb. However, minor passive sodium secretion occurs.
What is the permeability characteristic of the ascending limb?
The ascending limb reabsorbs sodium via the Na-K-Cl cotransporter but is impermeable to water.
What is the main function of the ascending limb of the Loop of Henle in sodium and water reabsorption?
The ascending limb reabsorbs sodium (Na⁺) and chloride (Cl⁻) via the Na⁺:K⁺:2Cl⁻ cotransporter but is impermeable to water.
What happens in the descending limb of the Loop of Henle?
Water is reabsorbed via AQP-1 water channels, but sodium (NaCl) is not reabsorbed.
Why is the descending limb permeable to water?
Because it expresses AQP-1 water channels, allowing passive water reabsorption.
What is secreted into the tubule in the descending limb of the Loop of Henle?
Sodium chloride (NaCl) is secreted into the tubule.
What is the osmolarity of the filtrate entering the Loop of Henle from the proximal convoluted tubule?
290 mosm/kg.
What is the primary function of the descending limb of the Loop of Henle?
picks up salt and loses water
What is the function of the loop of Henle?
The loop of Henle is a counter-current multiplier.
How does osmolality change in the medullary interstitial fluid?
There is a gradient of increasing osmolality as you move deeper into the medulla.
What is the osmolality of fluid entering the loop of Henle from the proximal tubule?
300 mosm/kg.
What is the osmolality of fluid leaving the loop of Henle?
100 mosm/kg.
What is the function of the vasa recta in the kidney?
It supplies blood without washing the gradient away, maintaining the osmotic gradient in the medulla.
Where is the vasa recta located?
It is found in the medulla, running alongside the Loop of Henle.
what are the osmolality values in vasa recta
300 in
325 out
What happens to sodium concentration in the interstitial fluid surrounding the vasa recta?
Sodium concentration is high around the turn of the vasa recta.
What is the main purpose of the counter-current exchange in the vasa recta?
It helps preserve the osmotic gradient in the medulla by allowing solute and water exchange between the descending and ascending limbs.
Where is urea freely filtered in the kidney?
In the renal corpuscle.
What happens to urea in the proximal tubule?
Urea undergoes passive reabsorption.
How is urea handled in the Loop of Henle?
Urea is secreted into the tubule via urea transporters.
Where does urea reabsorption occur in the nephron?
In the collecting duct via urea transporters.
What is the approximate percentage of filtered urea that is excreted?
Around 40-60%, depending on physiological conditions.
What hormone influences urea reabsorption in the collecting duct?
Anti-diuretic hormone (ADH).
Where does urea secretion occur?
In the loop of Henle.
Where does urea reabsorption take place?
In the collecting duct via urea transporters under the control of ADH.
How does urea recycling affect the kidney?
It contributes to the high osmolality in the medulla.
What two solutes contribute equally to the osmolality of the renal medulla interstitial fluid?
Urea and sodium.
What is the primary function of the Loop of Henle in sodium and water balance?
To separate sodium and water reabsorption.
Does the Loop of Henle reabsorb more sodium or water?
It reabsorbs more sodium than water.
How does the Loop of Henle contribute to osmolality in the medulla?
It creates a gradient of increasing osmolality in the medullary interstitial fluid by reabsorbing sodium and recycling urea.
what is the primary role of ADH in the collecting duct?
ADH regulates water reabsorption by inserting aquaporins (AQP2) into the principal cells of the collecting duct.
How does ADH stimulate water reabsorption in the collecting duct?
ADH binds to the V2 receptor, activates cAMP, and promotes AQP2 insertion into the apical membrane of principal cells.
Which aquaporins are involved in water movement in the collecting duct?
AQP2 is inserted into the apical membrane, while AQP3 and AQP4 allow water to move into the interstitial fluid.
How does ADH affect urine concentration?
ADH increases water reabsorption, leading to concentrated urine.
What is the function of the vasa recta in maintaining the concentration gradient?
The vasa recta supplies blood without washing away the osmotic gradient, preventing dilution of the medullary interstitium.
How does the presence or absence of ADH affect urine output?
With ADH, urine is concentrated due to water reabsorption; without ADH, urine remains dilute.
What two main factors influence the formation of concentrated urine?
1) High osmolality of the renal medulla interstitial fluid
2) Water permeability of the collecting duct in the presence of ADH
What is the main regulator of ADH secretion?
Plasma osmolality.
When does neural control become important in regulating ADH secretion?
When blood volume decreases by 5% or blood pressure decreases by 10%
Which hormone increases ADH secretion?
Angiotensin II.
What hormone decreases ADH secretion
Natriuretic peptides.
What was ADH originally called?
Vasopressin
what are the 2 functions of ADH
1 = maintains plasma osmolality by controlling water reabsorption at collecting duct
2 = restores blood pressure by causing constriction of systemic arterioles
What is osmolar clearance (C_osm)?
The volume of plasma cleared of osmotically active particles per unit time.
What is the formula for osmolar clearance?
What is the normal fasting osmolar clearance?
About 2-3 ml/min.
What is free water clearance (C_H2O)?
The ability of the kidneys to excrete dilute or concentrated urine.
What is the formula for free water clearance?
How does free water clearance (C_H2O) indicate urine concentration?
What is the possible range for free water clearance (C_H2O)?
-1.3 to 14.5 ml/min.
What does the term “Diabetes Insipidus” mean?
“Diabetes” comes from the Greek word diabainein, meaning “to pass through,” and “Insipidus” is Latin for “having no flavor.”
What are the 3 key characteristics of Diabetes Insipidus?
Polyuria (excessive urination, urine > 2L/day)
Polydipsia (excessive thirst)
Nocturia (frequent urination at night)
What are the two main types of Diabetes Insipidus?
Neurogenic (Central) – No ADH is secreted.
Nephrogenic – ADH is present, but kidneys do not respond to it.
What are the 2 causes of Neurogenic Diabetes Insipidus?
Congenital (genetic causes)
Trauma (e.g., head injury or brain tumor)
What are the causes of Nephrogenic Diabetes Insipidus?
Inherited (mutations in V2 receptor or aquaporin 2 channel)
Acquired (due to infection or drug side effects, e.g., lithium)
What is osmotic diuresis?
Increased urination due to small molecules (e.g., glycerol, mannitol, excess glucose) in the renal tubule lumen, preventing water reabsorption.
What are the key characteristics of osmotic diuresis?
Polyuria (excessive urination)
Polydipsia (excessive thirst)
What condition is osmotic diuresis typical of?
Untreated diabetes mellitus
What is the first step in the mechanism of osmotic diuresis?
Increased blood glucose
How does increased blood glucose contribute to osmotic diuresis?
What is the major intracellular cation in the body?
Potassium (K⁺)
What are the normal potassium concentrations in the body?
Extracellular fluid: 5 mM
Intracellular fluid: 150 mM
What is the main determinant of resting membrane potential?
The potassium gradient across the cell membrane
How much potassium is ingested daily?
40-120 mmoles per day
What processes are involved in renal handling of potassium?
Filtration, reabsorption, and secretion
How much potassium do the kidneys filter daily?
~800 mmoles/day
What percentage of filtered potassium is reabsorbed?
~95%
Where is potassium secreted in the nephron?
In the collecting duct, then excreted in urine
Where does the majority of potassium (K⁺) reabsorption occur in the nephron?
approx 65% In the proximal tubule
Is potassium reabsorbed actively or passively in the proximal tubule?
Passively
Which side of the tubular epithelial cell faces the filtrate?
The luminal side
Which side of the tubular epithelial cell faces the interstitial fluid?
The basolateral side
What percentage of potassium is reabsorbed in the thick ascending limb?
~30%
Which transporter is responsible for potassium reabsorption in the thick ascending limb?
Na⁺:K⁺:2Cl⁻ cotransporter (NKCC2 transporter)
What percentage of potassium is reabsorbed in the distal tubule?
5%
Which transporter is responsible for potassium reabsorption in the distal tubule?
K⁺-H⁺ exchanger
Where does potassium reabsorption occur in the distal tubule?
In the intercalated cells (Type A) of the distal tubule
Which cells reabsorb K⁺ in the collecting duct?
Intercalated cells (Type A) and distal cells
How do intercalated cells reabsorb K⁺?
In exchange for H⁺ (H⁺-K⁺ exchanger)
Which cells primarily secrete K⁺ in the collecting duct?
Principal cells
What are the two exit routes for K⁺ secretion in principal cells?
- K⁺ channels
- Renal Outer Medullary K⁺ channel (ROMK)
- Ca²⁺-activated big-conductance K⁺ channel (BK) - K⁺:Cl⁻ cotransporter
What charge do sodium (Na⁺) and potassium (K⁺) ions carry?
Both are positively charged ions.
How do sodium and potassium ions move across membranes?
they move through specific ion channels down their electrochemical gradient.
What are the two components of an electrochemical gradient?
Chemical gradient – Difference in ion concentration across a membrane.
Electrical gradient – Difference in charge across a membrane.
What affects potassium (K⁺) secretion by principal cells in the collecting duct?
Factors affecting Na⁺ entry through epithelial Na⁺ channels (ENaC).
How does aldosterone influence potassium secretion?
Aldosterone stimulates K⁺ channels, increasing K⁺ secretion.
How does tubular flow rate affect K⁺ secretion?
High flow rates favor K⁺ secretion.
How does acid-base balance influence K⁺ secretion?
Acidosis inhibits K⁺ secretion.
Alkalosis enhances K⁺ secretion
Acidosis inhibits K⁺ secretion.
Alkalosis enhances K⁺ secretion
3.5 to 5 mM.
What is hyperkalemia?
plasma potassium concentration greater than 5.5 mM.
What is hypokalemia?
Plasma potassium concentration below 3.5 mM.
What is obligatory water loss?
The minimum volume of urine lost daily, approximately 0.428 L/day.
What is oliguria?
Urine output below the obligatory water loss.
What is diuresis?
A large volume of urine.
What is water diuresis?
Urine that contains primarily water.
What is osmotic diuresis?
Urine containing an abnormal concentration of solutes plus water.
What is polyuria?
Excessive urine output (above 2.5 liters/day).
What is dilute urine?
Urine with osmolality less than plasma.
What is concentrated urine?
Urine with osmolality greater than plasma.
