4b: renal physio, urine formation, electrolyte balance, and hormonal regulation

Renal Physiology

Introduction

• Topics Covered:
    - Urine formation
    - Electrolyte balance
    - Hormonal regulation
    - Presented by Kathleen Miles

Learning Outcomes

• Understand the process of urine formation.

• Identify transport mechanisms in the nephron:
    - Active transport
    - Osmosis
    - Facilitated diffusion
    - Passive electrochemical gradients

• Describe nephron processes for fluid and electrolyte balance.

• Identify electrolytes reabsorbed and secreted by proximal and distal tubules.

• Explain the urine concentration system.

• Identify hormones related to kidney function and their effects.

Tubular Processing of Glomerular Filtrate

how the nephron modifies the raw filtrate through reabsorption and secretion to produce final urine

1. Tubular Reabsorption
      - Definition: The process that moves solutes and water out of the filtrate and back into the bloodstream.

2. Tubular Secretion
      - Definition: Waste products and substances are moved from the blood into the urine.

Tubular Reabsorption - Transport Mechanisms

• Components involved in reabsorption:
    - Interstitial fluid
    - Tubular epithelial cell
    - Basement membrane
    - Tubular lumen
    - Intercellular space
    - Peritubular capillary

Transport Mechanisms

• Types of Transport:
    - Passive Transport: Moves substances without energy.
      - Simple Diffusion: Movement of molecules from high to low concentration.
      - Facilitated Diffusion: Involves carrier proteins or channels.
    - Active Transport: Requires energy (ATP).
      - Primary Active Transport: Directly uses ATP.
      - Secondary Active Transport: Uses electrochemical gradients.
        - Contrasport (symport): Moves substances in the same direction.
        - Countertransport (antiport): Moves substances in opposite directions.
    - Pinocytosis: Cell drinking, ingesting liquid.

Bulk Flow

• Definition: Movement of large volumes of fluid and solutes due to a pressure gradient.

• Driven by hydrostatic and osmotic pressures.

• Water and electrolytes are reabsorbed through bulk flow in peritubular capillaries.

Additional Definitions

• Tubular Transport Maximum (Tm)
    - Maximum rate for the transport of a substance by renal tubules (mg/min) before it starts appearing in the urine.
    - Saturation: Specific carriers and enzyme systems become saturated during active transport.

• Examples of Tm-limited Reabsorption:
    - Glucose, amino acids, phosphates, sulphates.

• Examples of Tm-limited Secretion:
    - Para-aminohippuric acid (PAH), penicillin.

• Renal Threshold: (mg/dl)

  • for substances that have reobsorption Tm

  • plasma concentration where a substance first begins to appear in the urine

  • reflects the point where its filtered load starts to exceed the nephron’s Tm

Handling of Sodium (Na+)

• More than 99% of filtered Na+ is reabsorbed along the renal tubule.

Handling of Glucose by renal tubules

• Under normal conditions, 100% of filtered glucose is reabsorbed to prevent urinary loss.

• Glucose is reaborbed in the proximal tubule by specific transport proteins

• each transporter can only move glucose at a certain rate

• extra glucose above the threshold is excreted into the urine

Handling of Water

• Obligatory Reabsorption:
    - Independent of Antidiuretic Hormone (ADH)
    - 87% of filtered water reabsorbed passively by osmosis.

• Facultative Reabsorption:
    - Dependent on ADH
    - 12.5% of filtered water reabsorbed in certain renal segments.

Summary of Water Handling in Different Tubule Segments:

• Proximal Tubule: Reabsorbs 65% of filtered water secondary to solute reabsorption.

• Loop of Henle: Drives reabsorption due to high osmolarity of medullary interstitium; approximately 15% reabsorbed here.

• Late Distal Tubule & Cortical Collecting Duct: 2% of filtered water reabsorbed.

• Medullary Collecting Duct: Can reabsorb water under the influence of ADH.

Urine Concentration and Dilution

Requirements for Concentrated Urine Excretion:

1. Adequate ADH to increase permeability of late distal tubule, collecting tubule, and medullary duct.

2. Hyperosmotic Renal Medulla:
     - Countercurrent Multiplier: Function of Loop of Henle.
     - Countercurrent Exchanger: Function of vasa recta.
     - Passive Urea Diffusion: From the medullary duct.
     - Sluggish Medullary Blood Flow: About 1-2% of renal blood flow.

Countercurrent Multiplier and Exchanger

• Mechanisms:
    - Active and passive transport processes occurring in the Loop of Henle and vasa recta managing osmotic concentration.

Handling of Urea

• Proximal Tubule: Reabsorbs about 40% of filtered urea via passive diffusion.

• Approximately 40-60% of filtered urea is excreted, particularly from the late distal tubule and collecting duct that become impermeable to urea, raising its concentration.

Handling of Potassium (K+)

• Reabsorption primarily occurs in the proximal tubule and loop of Henle.

• Regulation: Final excretion is conducted by the distal tubule and collecting duct, which maintains serum K+ levels to prevent hyperkalemia or hypokalemia.

Handling of Calcium (Ca++)

• Reabsorption:
    - Proximal Tubule: 60-70% (transcellular)
    - Loop of Henle: 5% (paracellular)
    - Distal Convoluted Tubule: 10% (transcellular)
    - Connecting Tubule: 3-10% (transcellular)

Secretion of Hydrogen (H+) & Reabsorption of Bicarbonate (HCO₃)

• Proximal Tubule: Reabsorbs 85% of filtered HCO₃.

• Thick Ascending Limb of Loop of Henle: Reabsorbs 10% of filtered HCO₃.

• Collecting Duct: Reabsorbs 4.9% of filtered HCO₃.

Plasma Renal Clearance

volume of plasma comopletely cleared of a substance by the kidneys per unit time

reflectts how effectively the kidneys remove that substance

• Formula:
    $C_{r}=\frac{U\cdot V}{P}$
    - Cr: Renal Clearance
    - U: Urine concentration of the substance (mg/mL)
    - V: Urine flow rate (mL/min)
    - P: Plasma concentration of the substance (mg/mL)

high clearance → kidneys removes plasma efficiently

low clearance → kidneys retain in

a. substance is filtered at the glomerulus - whatever is filtered is excreted = GFR

b. filtration + partial absorption = less than GFR

c. iltration + complete reaborption = clearance 0, nothing appears in the urine

d. fitration + secretion - additional amounts are actively secreted = larger than GFR

Hormonal Regulation and Effects on the Kidneys

Additional Hormonal Functions of the Kidneys

• Renin: Regulates blood pressure.

• Erythropoietin (EPO):Stimulates red blood cell production in bone marrow.

• Vitamin D: Activation in kidneys supports calcium absorption in the gut, crucial for bone and muscle health.

Acknowledgments

• Thanks to the contributors for their information and insights on renal physiology.