Loop of Henle

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Questions and Answers

The kidney is capable of producing concentrated urine but not diluted urine

False

What is needed to form concentrated urine?

A hypertonic medullary interstitial is needed to form concentrated urine.

The short and long hoop of Henle contribute to urine concentration.

True

Match the broad function of each essential component needed for either concentrating/diluting urine.

Hypertonic medullary insterstitium = Allows excretion of concentrated urine Thick ascending limb and DCT = Allows excretion of dilute urine CT’s permeability to ADH = Determines final urine concentration Free bee = Free bee Signup and view all the answers

Which nephron segment reabsorbs bulk of the filtered solutes?

PCT Signup and view all the answers

Why/how is the PCT able to absorb the bulk of filtered solutes?

Due to its proximity to the peritubular capillary and the structure of proximal tubule Signup and view all the answers

What are the two pathways solutes are able to take during reabsorption?

The transcellular and paracellular pathway Signup and view all the answers

What structural feature of proximal tubule cells aids in the absorption process?

Brush borders formed by microvilli Signup and view all the answers

Which component contributes to keeping the peritubular capillaries in close contact with the proximal tubule?

High oncotic pressure Signup and view all the answers

What role do the coated pits on the proximal tubule cells serve?

Binding sites for substances undergoing receptor-mediated endocytosis Signup and view all the answers

How does the structure of tight junctions in proximal tubule cells influence their function?

They decrease permeability between cells. Signup and view all the answers

What is the primary force driving fluid movement at the peritubular capillaries?

Hydrostatic pressure pushes fluid out, while oncotic pressure pulls it in. Signup and view all the answers

Which type of nephron has long loops of Henle that extend into the inner medulla?

Juxtamedullary nephrons Signup and view all the answers

Which segment of the loop of Henle is primarily responsible for the reabsorption of sodium and chloride ions?

Thick ascending limb Signup and view all the answers

The thin segments of the loop of Henle are characterized by which of the following features?

Thin epithelial membranes and low metabolic activity Signup and view all the answers

The THIN loop of Henle has (HIGH/LOW) permeability to water.

The thin loop of Henle has HIGH permeability to water. Signup and view all the answers

What is the primary role of aquaporins (AQP-1) in the thin descending loop?

Allowing passive diffusion of water Signup and view all the answers

Which statement correctly describes the thin descending loop’s permeability characteristics?

Low permeability to sodium and increased permeability to water Signup and view all the answers

What effect does the reabsorption of water in the thin descending limb have on the tubular fluid?

It concentrates the tubular fluid. Signup and view all the answers

Why does the thin descending loop have a lesser number of mitochondria?

It requires less energy for metabolic activities. Signup and view all the answers

Which physiological outcome results from the characteristics of the thin descending limb?

Enhanced water retention in the body Signup and view all the answers

What effect does the reabsorption of sodium and chloride in the medullary thick ascending limb have on the tubular fluid?

It decreases osmolality of the tubular fluid. Signup and view all the answers

The medullary thick ascending limb is referred to as the 'diluting segment' primarily because it facilitates what process?

Dilutes tubular fluid by reabsorbing solutes without water. Signup and view all the answers

Which of the following best describes the permeability characteristics of both ascending limbs of Henle's loop?

Virtually impermeable to water. Signup and view all the answers

What physiological consequence arises due to the reabsorption process in the medullary thick ascending limb?

Increased concentration of the renal medullary fluid. Signup and view all the answers

Which of the following ions does the medullary thick ascending limb reabsorb in significant amounts?

Chloride. Signup and view all the answers

Match to the appropriate description of the LOH segments

Descending limb = Water is reabsorbed, low permeability to solutes, osmolality of tubular fluid gradually increases Ascending thin limb = Essentially impermeable to water and NaCl is reabsorbed Ascending thick limb = Virtually impermeable to water, NaCl reabsorption, dilution of tubule fluid, paracellular transport of Ca, Mg and Na Free bee = Free bee Signup and view all the answers

The ascending thin limb is present only in short loop nephrons

False Signup and view all the answers

What are the two relevant transporter systems in the mTAL?

It is the NKCC and ROMK Signup and view all the answers

Which ion is primarily transported by the NKCC in the mTAL against its concentration gradient?

Chloride Signup and view all the answers

What effect does furosemide have on the NKCC?

Inhibits NKCC function Signup and view all the answers

Which mechanism contributes to the positive potential in the tubular lumen created by NKCC activity?

Back leak of potassium via ROMK Signup and view all the answers

What is the primary energy source for the NKCC located on the apical side of the mTAL?

Sodium-potassium ATPase on the basolateral membrane Signup and view all the answers

Which hormone is known to stimulate the NKCC activity in the thick ascending limb?

Antidiuretic hormone (ADH) Signup and view all the answers

What is the primary role of the countercurrent exchange in the kidney?

To maintain a hypertonic environment in the medulla Signup and view all the answers

Which of the following statements accurately describes the function of the descending limb of the loop of Henle?

Passively reabsorbs water without solute movement Signup and view all the answers

What occurs due to the osmotic gradient generated by the countercurrent multiplier?

Increased concentration of the interstitial fluid in the medulla Signup and view all the answers

Which physiological feature primarily leads to the maintenance of high osmolality in the interstitial fluid of the renal medulla?

Balanced inflow and outflow of solutes and water Signup and view all the answers

What is primarily responsible for the differing permeability of the ascending and descending limbs of the loop of Henle?

Differences in epithelial cell structure and function Signup and view all the answers

What is the primary physiological effect of furosemide on the kidneys?

Increases urine and sodium excretion by blocking the NKCC transporter Signup and view all the answers

How does the presence of increased sodium in the tubular fluid affect water absorption?

Increases osmolality, leading to reduced water reabsorption Signup and view all the answers

What role does sodium play in urine formation when affected by furosemide?

Sodium increases the volume of filtrate due to its osmotic effect Signup and view all the answers

What is the mechanism by which furosemide affects the NKCC transporter?

Blocks the transport of sodium, potassium, and chloride into the renal cells Signup and view all the answers

Why does furosemide lead to an increase in urinary output?

It leads to increased osmolality in the tubular fluid, reducing water reabsorption Signup and view all the answers

Which transporter system is directly inhibited by thiazide diuretics in the distal convoluted tubule?

Sodium/Chloride co-transporter (NCC) Signup and view all the answers

What ions are primarily reabsorbed by the distal convoluted tubule?

Sodium, potassium, chloride, calcium and magnesium Signup and view all the answers

Which of the following correctly describes a feature of the distal convoluted tubule?

It shares structural characteristics with the medullary thick ascending limb (mTAL). Signup and view all the answers

Which ion does the sodium/chloride co-transporter (NCC) primarily facilitate reabsorption for?

Sodium Signup and view all the answers

What is the role of Calcium channels in the distal convoluted tubule?

Allowing calcium to enter the cell for reabsorption Signup and view all the answers

Which statement accurately describes the function of principal cells in the collecting ducts?

They reabsorb sodium through ENaC channels and water reabsorption is ADH dependent. Signup and view all the answers

What is the primary role of intercalated cells in the collecting ducts?

To maintain acid-base homeostasis through bicarbonate and hydrogen ions transport. Signup and view all the answers

What distinguishes type A intercalated cells from type B intercalated cells?

Type A cells secrete hydrogen ions while type B cells reabsorb them. Signup and view all the answers

Which transport systems are relevant to principal cells in terms of potassium excretion?

Potassium channels (ROMK) and epithelial sodium channels (ENaC). Signup and view all the answers

What characterizes the inner medullary collecting ducts compared to the late distal convoluted tubule?

The inner medullary collecting ducts reabsorb urea via specific transporters like UT-A1, A-3. Signup and view all the answers

Which statement accurately describes the role of urea in the kidney?

Urea contributes to the medullary hypertonicity, enhancing water reabsorption. Signup and view all the answers

What enhances urea reabsorption in the inner medullary collecting duct?

Anti-diuretic hormone (ADH) Signup and view all the answers

Which condition best describes the movement of urea in the descending thin limb?

Urea is secreted into the tubule by diffusion down its concentration gradient. Signup and view all the answers

How does sodium reabsorption influence the movement of water in the kidneys?

Sodium increases interstitial osmolality, leading to water reabsorption. Signup and view all the answers

What physiological challenge do terrestrial animals face regarding kidney function?

Desiccation or dehydration due to water loss. Signup and view all the answers

What is the approximate daily filtration volume for a 20 kg dog?

144 liters Signup and view all the answers

Which mechanism primarily contributes to the countercurrent multiplication system in the kidney?

The concurrent flow of filtrate in the descending and ascending limbs of Henle's loop. Signup and view all the answers

What is the primary function of aquaporins in the nephron?

Promoting water reabsorption throughout various nephron segments. Signup and view all the answers

How does the renal handling of ions like Na+ and Cl- contribute to urine concentration?

They create a gradient for water reabsorption. Signup and view all the answers

What is the primary impact of ADH on the collecting ducts?

It enhances water permeability. Signup and view all the answers

Which mechanism primarily contributes to the increase in medullary interstitial osmolality?

Urea recycling in the collecting duct. Signup and view all the answers

What happens to the osmolality of tubular fluid as it passes through the descending thin limbs of Henle's loop?

It gradually increases. Signup and view all the answers

What physiological condition triggers the release of ADH?

Dehydration leading to hyperosmolarity. Signup and view all the answers

What effect does aldosterone have on the principal cells in the collecting duct?

Increases K+ secretion. Signup and view all the answers

Which statement best describes the role of the countercurrent mechanism in the kidney?

It helps maintain a hypertonic medullary interstitium. Signup and view all the answers

What occurs when ADH levels are low in the kidneys?

Decreased permeability of collecting ducts to water. Signup and view all the answers

Which element is primarily responsible for the reabsorption of Na+ in the distal convoluted tubule?

ENaC channels. Signup and view all the answers

How does furosemide primarily affect the kidneys?

Blocks the NKCC activity in the thick ascending limb. Signup and view all the answers

Which condition allows the kidneys to produce hypotonic urine?

Increased fluid intake. Signup and view all the answers

What is the effect of the Na+/H+ exchanger in the proximal tubule?

It facilitates Na+ reabsorption and H+ secretion. Signup and view all the answers

What primarily determines the final osmolality of urine in the kidneys?

The level of ADH present. Signup and view all the answers

What role does the NKCC (Na+, K+, Cl-) transporter play in the kidney?

Increases the osmolality of the tubular fluid. Signup and view all the answers

What is the primary mechanism that allows the kidneys to produce concentrated urine?

Countercurrent mechanism enhancing medullary hypertonicity Signup and view all the answers

Which nephron segment is primarily responsible for the active reabsorption of NaCl that contributes to medullary hypertonicity?

Thick ascending limb of the loop of Henle Signup and view all the answers

What effect does the secretion of antidiuretic hormone (ADH) have on urine concentration?

Enhances water reabsorption in the collecting duct Signup and view all the answers

How does countercurrent exchange in the vasa recta contribute to maintaining medullary interstitial hypertonicity?

By preventing dilution of the medullary interstitium while allowing water removal Signup and view all the answers

What is the consequence of NaCl reabsorption by the medullary thick ascending limb on the tubular fluid?

Dilutes the tubular fluid as it leaves this segment Signup and view all the answers

Study Notes

Proximal Tubule Structure

Proximal tubule cells are polarized, with apical and basolateral membranes.
The apical membrane has brush borders (microvilli), which increase surface area for absorption.
The basolateral membrane has infoldings, which facilitate transport of reabsorbed substances.
Tight junctions, specifically zonula occludens, join adjacent proximal tubule cells, forming a barrier that prevents leakage.
Coated pits on the cell membrane contain binding sites for substances reabsorbed by receptor-mediated endocytosis.
Peritubular capillaries are in close contact with the proximal tubule, facilitating exchange of substances.
Peritubular capillaries have high oncotic pressure and low hydrostatic pressure, promoting reabsorption from the proximal tubule.
The high oncotic pressure in peritubular capillaries results from high protein concentration, pulling fluid back into the capillaries.
The low hydrostatic pressure in peritubular capillaries minimizes fluid pressure pushing fluid out of the capillaries.

Loop of Henle Structure

The Loop of Henle (LoH) is a structure within the nephron that arises after the proximal tubule.
The LoH is composed of four segments:
- Thick descending limb (some authors don't consider this segment, and call it the "straight part" of the proximal tubule)
- Thin descending limb
- Thin ascending limb
- Thick ascending limb, also known as the medullary thick ascending limb (mTAL)
The thin segments have thin epithelial membranes, no brush borders, few mitochondria, and low metabolic activity.

Nephron Types

Two types of nephrons exist:
- Juxtamedullary nephrons:
  - Long loops of Henle that extend into the inner medulla
- Cortical nephrons:
  - Short loops that extend only into the outer medulla.
  - Do not have a thin ascending limb.
Long loops of Henle are particularly important for urine concentration.
Understanding these differences in nephron types is crucial for understanding their functions.

Key Concepts

Solution: A substance dissolved in a liquid.
Solute: The dissolved substance.
Solvent: The liquid of the solution.
Osmolality: The number of osmoles (Osm) of solute per kilogram of solvent.
- More suitable for living organisms because volume is temperature-dependent (Osm/Kg water).
Osmolarity: The concentration of all osmotically active particles in a solution, expressed as osmoles per liter of solution (Osm/L).
- Osmolarity (osM) = molarity (M) x dissociation factor
One mole of any substance has Avogadro's number (6.02 × 10^23) of particles.
Molarity (M) of a solution is a measure of concentration, with one mole of solute per liter of solution.

Osmolality

Represents the number of osmoles of solute per kilogram of solvent
More suitable for living organisms as it is temperature independent
Osmolality is a measure of the solute concentration in a solution that takes into account the number of particles that contribute to the osmotic pressure

Osmolarity

Represents the number of osmoles of solute per liter of solution
Osmolarity is a measure of the solute concentration in a solution that takes into account the number of particles that contribute to the osmotic pressure
It is temperature dependent.

Thin Descending Loop of Henle

The thin descending loop of Henle does not have a brush border.
The thin descending loop of Henle has fewer mitochondria compared to other parts of the nephron due to reduced metabolic activity.
The thin descending loop of Henle is primarily involved in water reabsorption through simple diffusion.
The thin descending loop of Henle expresses aquaporin-1 (AQP-1) in the apical membrane, facilitating water reabsorption.
The thin descending loop of Henle exhibits reduced permeability to sodium, chloride, and urea.
As water is reabsorbed, the concentration of NaCl within the tubular lumen increases, contributing to tubular fluid concentration.
The thin descending loop plays a crucial role in concentrating the tubular fluid as it descends into the hypertonic renal medulla.

Ascending Limb of Henle's Loop

Both thin and thick ascending limbs are impermeable to water.
The thin ascending limb has low reabsorptive capacity.
The medullary thick ascending limb (mTAL) reabsorbs significant amounts of sodium, chloride, potassium, calcium, bicarbonate, and magnesium.
The mTAL is metabolically active due to its thick epithelial cells.
mTAL reabsorbs NaCl without water, leading to diluted tubular fluid and a concentrated renal medulla.
The mTAL is known as the "diluting segment" due to its role in diluting tubular fluid and maintaining the hypertonicity of the renal medulla.

Sodium, Potassium, Chloride Cotransporter (NKCC)

The NKCC protein is located on the apical side of the mTAL cells (the thick ascending limb of the loop of Henle)
The NKCC is inhibited by furosemide (loop diuretics)
NKCC utilizes energy from the sodium-potassium ATPase pump, which is located on the basolateral membrane.
NKCC moves potassium and chloride against their concentration gradient into the cell.
Potassium and chloride then passively diffuse out of the cell along their concentration gradient.
A small amount of potassium leaks back into the tubular lumen through ROMK channels, which creates a positive potential in the lumen.
This positive potential facilitates the paracellular movement of other positive ions, including magnesium and calcium, into the interstitium.
Antidiuretic hormone (ADH) stimulates the NKCC, resulting in increased reabsorption of sodium, chloride, and potassium in the TAL.

Countercurrent Mechanisms

Countercurrent mechanisms utilize opposing fluid flow to generate and maintain concentration gradients.
Simple exchange systems involve parallel fluid flow with exchange only at high gradient points.
Countercurrent exchange involves fluids flowing in opposite directions, enabling exchange along the entire length.
The Loop of Henle in the kidney exemplifies countercurrent exchange, utilizing a hairpin-shaped loop.
In the Loop of Henle, the fluid exiting is only slightly different from the entering fluid due to continuous exchange.
The countercurrent multiplier in the Loop of Henle is facilitated by a sharp hairpin turn and opposing fluid flow.
The descending limb of the Loop of Henle is permeable to water, while the ascending limb reabsorbs solutes without water, generating an osmotic gradient of approximately 200 mOsm/L.
Water reabsorption in the interstitium occurs via the vasa recta, preventing dilution and swelling of the medulla.
The high osmolality of the medullary interstitial fluid is maintained by a balanced inflow and outflow of solutes and water.

Furosemide Mechanism

Furosemide inhibits the NKCC transporter in the ascending limb of the loop of Henle.
Inhibition of NKCC prevents sodium, potassium, and chloride from entering the cells of the ascending limb.
This results in an increased sodium concentration in the tubular fluid.
Sodium is an effective osmole, so increased sodium concentration in the tubule increases osmolality.
Increased osmolality in the tubular fluid reduces water reabsorption.
Less water reabsorption leads to more water remaining in the tubular fluid.
Ultimately, the result is increased urine excretion and sodium excretion.

Distal Convoluted Tubule (DCT)

Resembles the medullary thick ascending limb (mTAL) structurally
Reabsorbs a significant amount of ions including: Sodium, potassium, chloride, calcium, and magnesium
Employs various transporter systems for these reabsorption processes:
- Calcium channels
- Sodium/chloride co-transporter (NCC)
- Chloride and potassium channels
- Sodium/calcium exchanger (NCX)
Thiazide diuretics inhibit the NCC, thus reducing sodium and chloride reabsorption.

Late Distal Convoluted Tubule & Cortical Collecting Duct

Water reabsorption is regulated by aquaporins and anti-diuretic hormone (ADH).
High ADH levels increase water permeability, leading to increased water reabsorption.

Inner Medullary Collecting Ducts

Urea reabsorption occurs through specific urea transporters (UT-A1, A-3).

Collecting Duct Cell Types

Principal cells:
- Responsible for sodium chloride (NaCl) reabsorption.
- Have apical epithelial sodium channels (ENaC), which are induced by aldosterone.
- Involve ROMK (renal outer medullary potassium channel) for potassium excretion.
Intercalated cells:
- Crucial for acid-base homeostasis.
- Two types:
  - Type A cells secrete hydrogen and reabsorb bicarbonate.
  - Type B cells reabsorb hydrogen and secrete bicarbonate.

Urea Recycling

Urea is a waste product of protein metabolism.
It is eliminated through the urinary system and helps maintain medullary hypertonicity.
The kidneys reabsorb some urea, but the majority that is not reabsorbed is excreted in the urine.
Urea reabsorption can occur in the proximal tubule but is not regulated.
Urea is secreted into the tubule via the descending thin limb.
It moves down a concentration gradient from the vasa recta, through the interstitium, to the thin descending limb.
Antidiuretic hormone (ADH) enhances urea reabsorption in the inner medullary collecting duct (IMCD).
ADH upregulates the urea transporter proteins UT-A1 and UT-A3, increasing urea reabsorption.
Enhanced urea accumulation in the medullary interstitium contributes to medullary interstitial osmotic pressure and promotes water reabsorption.

Medullary Hypertonicity and Urine Concentration

The kidney's ability to concentrate urine depends on a hypertonic medullary interstitium.
This gradient is established through selective reabsorption and secretion of solutes, primarily NaCl and urea.
The thin descending limb of Henle's loop is highly permeable to water but less permeable to solutes, leading to an increase in tubular fluid osmolality as water is reabsorbed.
The thick ascending limb is impermeable to water but actively reabsorbs NaCl, further increasing the osmolality of the interstitium.
The late distal tubule (DT) and cortical collecting duct (CCD) water permeability is regulated by ADH.
In the presence of ADH, water permeability is increased leading to concentrated urine.
In the absence of ADH, water permeability is decreased resulting in diluted urine.
Urea recycling plays a crucial role in establishing and maintaining medullary hypertonicity.

Water Reabsorption in the Kidney

The kidney's ability to reabsorb water plays a crucial role in water balance and maintaining plasma tonicity.
The proximal tubule reabsorbs water through aquaporins and solute reabsorption.
The thin descending limb of Henle's loop reabsorbs water via osmosis, driven by the increasing medullary interstitial osmotic pressure.
The collecting duct carries out the final major water reabsorption, which is regulated by ADH.
The countercurrent mechanism in the vasa recta prevents dilution of the medullary interstitium by removing water without disrupting the osmolality gradient.

Antidiuretic Hormone (ADH)

ADH (also known as vasopressin) is produced in the hypothalamus and transported to the posterior pituitary for release.
It acts on the kidney by increasing water permeability in the collecting duct, leading to water reabsorption.
ADH also stimulates sodium, chloride, and potassium reabsorption in the thick ascending limb (TAL) and increases urea reabsorption in the collecting duct.
It is triggered by hyperosmolarity, decreased atrial receptor firing, angiotensin II, and sympathetic stimulation.

Aldosterone

Aldosterone is a steroid hormone produced in the adrenal cortex and is part of the renin-angiotensin-aldosterone system (RAAS).
It targets the principal cells in the collecting duct.
Aldosterone increases Na+ reabsorption by increasing the activity of the sodium channel (ENaC) and the Na+,K+-ATPase pump.
It increases K+ secretion by stimulating the potassium channels ROMK and BK.

Angiotensin II

Angiotensin II is a potent vasoconstrictor that also plays a role in blood volume regulation.
It acts directly on the kidneys to increase Na+ reabsorption in various segments, including the proximal tubule, TAL, and distal collecting duct.
It directly affects the adrenal glands stimulating aldosterone production.

Summary Statements

The kidneys play a crucial role in maintaining water balance by adjusting urine concentration and promoting water reabsorption.
The proximal tubule reabsorbs over 60% of filtered water, setting the stage for further water reabsorption in the nephron.
The kidney can produce both concentrated and diluted urine based on the body's water needs.
A hypertonic medullary interstitium is essential for generating concentrated urine.
Short-loop and long-loop nephrons contribute differently to urine concentration.
NaCl reabsorption by the medial thick ascending limb (mTAL) is crucial for medullary hypertonicity.
Urea reabsorption in the inner medullary collecting duct and urea recycling further enhance medullary hypertonicity.
The countercurrent mechanism amplifies medullary interstitial osmolality by creating a gradient of increasing osmolality from the cortex to the medulla.
Countercurrent exchange in the vasa recta allows for water removal from the medullary interstitium without reducing the hypertonic gradient.
Active NaCl reabsorption in the TAL and DCT dilutes the tubular fluid.
ADH regulates collecting duct water permeability, ultimately determining the final urine osmolality.

Kidney Water Balance

Kidneys play a crucial role in maintaining water balance within the body.
The proximal tubule (PT) reabsorbs more than 60% of the filtered water.
The kidney can create both concentrated and diluted urine depending on the body's needs.
A hypertonic medullary interstitium is essential for the formation of concentrated urine.
Short-loop and long-loop nephrons have distinct roles in urine concentration.
Sodium chloride (NaCl) reabsorption by the thick ascending limb (TAL) contributes to medullary hypertonicity.
Urea reabsorption by the inner medullary collecting duct (IMCD) and urea recycling further enhance medullary hypertonicity.
The countercurrent mechanism increases medullary interstitial osmolality.
Countercurrent exchange in the vasa recta removes water from the medullary interstitium without reducing medullary interstitial hypertonicity.
Active NaCl reabsorption in the TAL and distal convoluted tubule (DCT) dilutes the tubular fluid.
Antidiuretic hormone (ADH) regulates collecting duct water permeability, ultimately determining the final urine osmolality.

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