Lecture 2: Kidney Structure and Function II Flashcards

1
Q

How does the kidney produce highly concentrated urine despite plasma osmolarity being around 300?

A
  • By creating an osmotic gradient in the renal medulla through the countercurrent mechanism.
  • This mechanism involves the loop of Henle, which establishes a gradient of increasing osmolarity from the cortex to the medulla.
  • The descending limb of the loop of Henle is permeable to water, allowing water to pass out of the tubule and into the interstitial fluid, concentrating the tubular fluid.
  • The ascending limb actively transports ions out of the tubule, creating a hypertonic interstitial fluid.
  • As the collecting duct passes through this hypertonic medullary interstitium, water is reabsorbed osmotically, resulting in the production of concentrated urine.
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2
Q

What is the minimal amount of urine produced, and why is it necessary?

A
  • The minimal amount of urine produced is approximately 500 mL per day.
  • This obligatory urine volume is needed to excrete waste solutes, which typically amount to around 600 milliosmoles per day.
  • The kidneys need to eliminate this waste to maintain proper physiological balance.
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3
Q

What is the maximum urine production per day, and why is it important?

A
  • The maximum urine production per day is around 20,000 mL.
  • This large range of urine production allows the kidneys to rapidly respond to changes in water intake or loss, helping to maintain fluid and electrolyte balance in the body.
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4
Q

What is diurnal variation in urine production?

A
  • Diurnal variation refers to the fluctuation in urine production throughout the day.
  • Typically, urine production is higher during the day and lower at night, reflecting variations in fluid intake, activity levels, and hormonal influences.
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5
Q

What factors determine the osmotic potential of the kidney interstitium, particularly in the medulla?

A
  • The osmotic potential of the kidney interstitium, especially in the medulla, depends on the concentration of urea and sodium chloride (NaCl).
  • High concentrations of these substances in the interstitium drive the movement (reabsorption) of water from the collecting ducts, especially in the presence of antidiuretic hormone (ADH).
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6
Q

How does urea recirculation contribute to the osmotic gradient in the kidney?

A
  • Urea is actively reabsorbed in the collecting ducts and then secreted back into the tubular fluid in the thin descending limb of the Loop of Henle.
  • This urea recirculation process, along with the active reabsorption of sodium ions and the passive movement of water, helps establish and maintain the osmotic gradient in the medulla.
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7
Q

What role do the Loop of Henle and vasa recta play in generating and maintaining the osmotic gradient?

A
  • The Loop of Henle actively transports sodium ions out of the tubular fluid in the ascending limb, creating a concentration gradient in the interstitium.
  • The vasa recta, specialized capillaries surrounding the Loop of Henle, help maintain the osmotic gradient by preventing the rapid washout of solutes from the interstitium.
  • Together, these structures play crucial roles in generating and sustaining the osmotic gradient necessary for water reabsorption and the production of concentrated urine in the kidney.
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8
Q

How is the increasing osmotic gradient in the medullary interstitial fluid formed?

A
  • Sodium ions (Na⁺) and chloride ions (Cl⁻) are actively transported into the medullary interstitial fluid by symporters in the thick ascending limb of the Loop of Henle (LoH), along with urea recycling.
  • Osmosis is inhibited due to reduced permeability of the cells to water, particularly in the descending limb of the LoH, resulting in the establishment of a countercurrent multiplier.
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9
Q

What role does the ascending limb of the LoH play in concentrating ions?

A
  • The ascending limb actively concentrates Na⁺ and Cl⁻ ions by secreting Na⁺ and potassium ions (K⁺) via transporters.
  • There is no osmosis in the ascending limb, contributing to the concentration of ions in the medullary interstitial fluid.
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10
Q

How is the osmotic gradient further enhanced?

A
  • The continued movement of fluid through the tubules leads to a constant build-up of ions in the medullary interstitial fluid.
  • This process results in the formation of an osmotic gradient, increasing from approximately 300 milliosmoles per liter (mOsm/L) to around 1200 mOsm/L.
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11
Q

Why do animals in desert environments often have relatively long LoH?

A
  • Animals in desert environments may have longer LoH because a longer LoH allows for greater urine concentration, which is advantageous in conserving water in arid conditions.
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12
Q

What is the osmolarity gradient down the Loop of Henle?

A

The osmolarity gradient descends to approximately 1200 milliosmoles per liter (mOsm/L) at the bottom of the Loop of Henle. This highly concentrated environment creates a strong osmotic potential, enabling the kidney to reabsorb water and produce concentrated urine.

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13
Q

What is the role of the vasa recta in relation to the Loop of Henle?

A
  • The vasa recta is the blood vessel system that surrounds the Loop of Henle. Originating from the afferent arteriole, it forms a network of vessels that run parallel to the Loop of Henle, resembling a U-shaped configuration.
  • This U-shaped structure of the vasa recta is crucial because it allows the blood vessels to closely follow the shape of the Loop of Henle. This arrangement prevents dissipation of the osmotic and ionic gradients established by the counter-current multiplier mechanism.
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14
Q

How is the osmotic gradient produced in the kidney?

A

The osmotic gradient is generated by the counter-current multiplier mechanism, which involves the active transport of ions, such as sodium (Na⁺) and chloride (Cl⁻), in the Loop of Henle. This process, coupled with passive water movement, results in the creation of a highly concentrated medullary interstitial fluid. This gradient allows for efficient water reabsorption and urine concentration.

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15
Q

What is the role of renin in the renin-angiotensin-aldosterone system (RAAS)?

A

Renin is secreted by juxtaglomerular cells in response to low blood volume and blood pressure. It initiates the conversion of angiotensinogen into angiotensin I.

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16
Q

What are the effects of angiotensin II in the body?

A

Angiotensin II is a potent vasoconstrictor that causes constriction of both afferent and efferent arterioles, leading to a decrease in glomerular filtration rate (GFR). It also increases the reabsorption of sodium (Na+), chloride (Cl-), and water by activating Na+/H+ antiporters. Additionally, angiotensin II stimulates the adrenal cortex to release aldosterone, which acts to increase water retention, thereby increasing blood volume and pressure.

17
Q

What is the physiological response to dehydration, decreased blood volume, and decreased blood pressure?

A
  • Dehydration, decreased blood volume, and decreased blood pressure are detected by juxtaglomerular cells in the kidney, leading to an increase in renin secretion.
  • Renin acts on angiotensinogen released by the liver to produce angiotensin I, which is then converted to angiotensin II by angiotensin-converting enzyme (ACE) primarily found in the lungs.
  • Angiotensin II causes vasoconstriction, leading to an increase in blood pressure until it returns to normal levels.
  • Angiotensin II also reduces glomerular filtration rate (GFR).
  • Additionally, angiotensin II stimulates the release of aldosterone, which increases blood volume by promoting sodium and water retention.
  • Overall, the net effect of the renin-angiotensin-aldosterone system is to increase blood volume and pressure via vasoconstriction and increased fluid retention.
18
Q

How is high blood pressure treated?

A
  • High blood pressure can be treated by targeting two main mechanisms: reducing blood volume and reducing vasoconstriction.
  • One approach to lowering blood pressure is to decrease blood volume through diuretics, which increase urine output and thereby reduce the volume of fluid circulating in the bloodstream.
  • Another approach is to reduce vasoconstriction, which can be achieved by blocking the production of angiotensin II. Angiotensin-converting enzyme (ACE) inhibitors, such as lisinopril and enalapril, inhibit the conversion of angiotensin I to angiotensin II. By blocking this conversion, ACE inhibitors effectively reduce vasoconstriction and lower blood pressure.
  • Therefore, medications like ACE inhibitors are commonly used in the treatment of hypertension to prevent the formation of angiotensin II and its potent vasoconstrictive effects.
19
Q

What are diuretics and how do they work?

A

Diuretics are substances that promote the loss of sodium and water from the body, ultimately leading to increased urine production.

20
Q

What are the types of diuretics?

A
  • Diuretics are substances that promote the loss of sodium and water from the body, ultimately leading to increased urine production.
  • There are several types of diuretics:
  • What are the types of diuretics?
    • Natural diuretic
      • Alcohol: increase urine production by inhibiting the ADH release and blocking the reabsorption of water in the kidneys.
    • Osmotic diuretics
      • E.g. mannitol
      • Create an osmotic force that prevents the reabsorption of water in the renal tubules, leading to increased urine output.
    • Loop diuretics
      • Furosemide
      • Most potent diuretics available.
      • They work by inhibiting the sodium-potassium-chloride cotransporter in the thick ascending limb of the loop of Henle, thereby preventing the reabsorption of sodium and chloride ions.
      • This disruption of ion transport disrupts the medullary concentration gradient, leading to increased urine output.
    • Thiazide diuretics
      • E.g. hydrochlorothiazide
      • Act on the DCT of the nephron.
      • They inhibit the sodium-chloride symporter in the DCT, reducing the reabsorption of sodium and chloride ions and promoting diuresis.
    • Potassium-sparing diuretics
      • E.g. spironolactone
      • Work by antagonizing the aldosterone receptor in the late distal tubule and collecting ducts.
      • By blocking aldosterone’s effects, these diuretics reduce sodium reabsorption and potassium secretion, leading to increased sodium and water excretion while sparing potassium loss.