Renal Physiology: Glucose & Osmolarity

Glucose Reabsorption & Renal Threshold

• All filtered glucose is usually reabsorbed in the proximal convoluted tubule (PCT).
• Renal threshold: If blood glucose exceeds 180mg/dL, the transport maximum (Tm) is exceeded, leading to glucose in the urine.
• This indicates hyperglycemia, often seen in diabetes mellitus.

Osmolarity Changes in the Nephron

• Filtrate entering the loop of Henle has an osmolarity of approximately 300 mOsm (isotonic).
• The filtrate becomes hypertonic (~1200 mOsm) at the bottom of the loop due to water reabsorption in the descending limb.
• Filtrate becomes hypotonic (~100 mOsm) after leaving the ascending limb, where Na⁺, K⁺, and Cl⁻ are reabsorbed without water.

Countercurrent Multiplier System

• Function: Establishes the vertical osmotic gradient in the medulla, critical for concentrating urine.
• Mechanism: The descending limb allows water to leave, while the ascending limb actively transports ions out and is impermeable to water.
• This creates a progressively higher osmolarity in the medulla.

Ion Recycling in the Thick Ascending Limb

• Most potassium brought into cells by the NKCC2 transporter is recycled back into the tubular lumen.
• This helps maintain adequate K⁺ in the lumen for NKCC2 function.
• The recycling creates a positive charge in the lumen, driving the paracellular reabsorption of Ca²⁺ and Mg²⁺.

Lasix (Furosemide)

• A loop diuretic that inhibits the NKCC2 transporter in the thick ascending limb.
• By blocking NKCC2, Lasix prevents Na⁺, K⁺, and Cl⁻ reabsorption.
• This disrupts the medullary osmotic gradient and increases urine output.
• It is used to treat fluid retention and hypertension.

The Collecting Duct and ADH

• The collecting duct reabsorbs water based on the medullary osmotic gradient and ADH (antidiuretic hormone) presence.
• ADH increases water permeability in the collecting duct by adding aquaporins.
• This concentrates the urine.
• Without ADH, urine remains dilute.

Glucose Reabsorption and Renal Threshold

• Glucose reabsorption: Typically, all filtered glucose is reabsorbed in the proximal convoluted tubule (PCT).
• Renal threshold: If blood glucose levels exceed approximately 180 mg/dL, the transport maximum (Tm) for glucose reabsorption is reached, resulting in glucose appearing in the urine.
• Hyperglycemia: This indicates hyperglycemia, often seen in conditions like diabetes mellitus.

Osmolarity Changes in the Nephron

• Entering the Loop of Henle: The filtrate entering the loop of Henle has an osmolarity of approximately 300 mOsm (isotonic with plasma).
• Bottom of the Loop: The filtrate becomes hypertonic (~1200 mOsm) due to water reabsorption in the descending limb.
• Leaving the Ascending Limb: As Na⁺, K⁺, and Cl⁻ are reabsorbed without water in the thick ascending limb, the filtrate becomes hypotonic (~100 mOsm).

Countercurrent Multiplier System

• Function: The countercurrent multiplier system in the loop of Henle establishes the vertical osmotic gradient in the medulla, essential for concentrating urine.
• Mechanism: The descending limb allows water to leave, while the ascending limb actively transports ions out but is impermeable to water. This creates a progressively higher osmolarity in the medulla.

Ion Recycling and Lumen Charge in the Thick Ascending Limb

• Potassium Recycling: Most potassium brought into cells by the NKCC2 transporter is recycled back into the tubular lumen.
• Lumen Positive Charge: This recycling creates a positive charge in the tubular lumen, driving the paracellular reabsorption of other cations like calcium (Ca²⁺) and magnesium (Mg²⁺).

Lasix (Furosemide) Mechanism of Action

• Target: Lasix is a loop diuretic that inhibits the NKCC2 transporter in the thick ascending limb of the loop of Henle.
• Effect: Blocking NKCC2 prevents Na⁺, K⁺, and Cl⁻ reabsorption, disrupting the medullary osmotic gradient and leading to increased urine output, commonly used to treat fluid retention and hypertension.

Role of the Collecting Duct and ADH

• Water Reabsorption: The collecting duct reabsorbs water based on the medullary osmotic gradient and the presence of antidiuretic hormone (ADH).
• ADH Influence: When ADH is present, it increases water permeability in the collecting duct by adding aquaporins, allowing water to be reabsorbed, concentrating the urine. Without ADH, the urine remains dilute.

Potassium Recycling in the Thick Ascending Limb

• NKCC2 Function: In the thick ascending limb, potassium (K⁺) recycling into the tubular lumen is crucial for maintaining the NKCC2 transporter’s activity.
• Net Positive Voltage: This recycling creates a positive voltage in the lumen, driving the paracellular reabsorption of other cations (e.g., Ca²⁺ and Mg²⁺).

Medullary Osmotic Gradient and the Collecting Duct

• Purpose: The vertical osmotic gradient (VOG) in the medulla, established by the loop of Henle, is essential for allowing water reabsorption in the collecting duct.
• Water Reabsorption: When ADH is present, water moves from the collecting duct into the hypertonic medullary interstitial fluid, enabling the kidney to produce concentrated urine.

Explore the critical concepts of glucose reabsorption and renal threshold in the nephron. Understand how osmolarity changes throughout the nephron and the role of the countercurrent multiplier system in urine concentration. This quiz is perfect for students studying renal physiology in advanced biology courses.