Kidney Function and Regulation

Renal Structure and Function

Functional Unit of the Kidney

  • Nephron:
    • Basic unit of kidney function; approximately one million per kidney.
    • Components include tubule and associated vasculature (arterioles & capillary beds).

Elements of Renal Function

  • Bowman’s Capsule / Glomerulus:

    • Function: Formation of protein-free ultrafiltrate of plasma.

  • Proximal Convoluted Tubule (PCT):

    • Function: Major site for reabsorption of water and solutes into interstitial fluid (ISF) and then into peritubular capillaries.

  • Loop of Henle:

    • Function: Produces highly concentrated interstitial fluid in the medulla.

  • Distal Tubule / Collecting Ducts:

    • Function: Regulation of solute concentrations and reabsorption; some solutes are secreted.
    • Medullary Collecting Duct: Regulates water content.

Glomerular Filtration Rate (GFR)

  • Definition: Amount of plasma that enters Bowman’s capsule per minute.
  • GFR comparison: Urine output is about 1% of GFR.

Arterioles Effect

  • Efferent Arteriole:
    • Increases glomerular capillary hydrostatic pressure (enhances net filtration).
    • Decreases peritubular capillary hydrostatic pressure (inhibits net reabsorption).

Kidney Tubular Processes

Key Processes
  • Filtration: Movement of fluid from blood to tubule (occurs in glomerulus).
  • Reabsorption: Movement of substances from tubule back to blood (primarily in PCT).
  • Secretion: Movement of substances from blood to tubule (in various nephron segments).
Podocytes Function
  • Podocytes: Form the inner layer of Bowman’s capsule, with filtration slits allowing the passage of water and ions, but not proteins.

Sodium & Water Reabsorption

Locations in Nephron
  • Sodium Pumps: Located on basolateral membranes of nephron epithelial cells.
  • Sodium Co-Transporters and Ion Channels: Found on apical membranes; vary by nephron region.
Transport Mechanisms
  • Na+ Reabsorption: Mediated by tubular transport processes.
  • Cl- Reabsorption: Typically follows Na+ due to electrical neutrality.
  • Water Reabsorption: Occurs via osmosis, following solute reabsorption.
Transport Maximum (Tm)
  • Tm: Tubular Maximum; the maximum capacity of carrier proteins.
  • Filtered Load: Amount of substance entering the tubules per minute; the relationship compared to Tm helps understand saturation levels, with glucose commonly used as an example.

Osmolarity and Urine Concentration

  • Normal Plasma Osmolarity: 290-300 mOsm/L.
  • Loop of Henle Properties:
    • Countercurrent: Fluid flows down and up in opposing directions.
    • Thick Ascending Limb: Actively transports NaCl out; impermeable to water.
    • Descending Limb: Freely permeable to water; impermeable to NaCl.
Urine Concentration
  • Maximum urine concentration in humans can reach approximately 1200-1400 mOsm/L, due to the countercurrent multiplier effect in juxtamedullary nephrons.
  • Dilute Urine Production: Achieved by allowing water to remain in collecting ducts leading to a concentration of 30-50 mOsm/L.

ECF Osmolarity Regulation Reflex

  • Components:
    • Sensors: Detect osmotic changes.
    • Integrator: Kidneys, particularly juxtaglomerular apparatus (JGA) smooth muscle cells.
    • Effectors: Principal cells in cortical collecting duct, along with behavioral responses (drinking, salt intake).

Extracellular Fluid (ECF) and Sodium Regulation

  • Relationship: ECF [Na+] regulates plasma volume. Changes in Na+ affect fluid shifts and plasma volume.
  • Regulation of [Na+]: Focuses on active transport as Cl- moves passively.
Juxtaglomerular Apparatus (JGA) Components
  • Tissues:
    • Afferent arteriolar smooth muscle cells.
    • Macula densa cells: Sense tubular [NaCl] and signal to smooth muscle.
Renin Formation Stimuli
  • Increased renal sympathetic nerve activity.
  • Decreased arterial pressure.
  • Decreased GFR leading to reduced flow to macula densa.
Effects of Angiotensin II (AT II)
  • Increases plasma renin levels.
  • Promotes vasoconstriction and fluid retention.
Sensors and Effectors for ECF Volume Regulation
  • Sensors: High pressure (arterial) and low pressure (venous) receptors.
  • Effectors: JGA smooth muscle cells, principal cells in cortical collecting duct.

Calcium Regulation in Plasma

Sensor Location
  • Parathyroid Glands: Senses plasma [Ca2+].
Relationship of Calcium and PTH
  • Low plasma [Ca2+] stimulates PTH release.
Effectors of Calcium Regulation
  • Gut: Increases absorption of Ca2+.
  • Bone: Increases resorption of Ca2+.
  • Kidney: Enhances reabsorption of Ca2+ under PTH influence.

Potassium Regulation

Importance of [K+] Regulation
  • Critical for maintaining the resting membrane potential of excitable cells.
K+ Secretion Mechanism
  • Normally secreted due to dietary excess; occurs in cortical collecting duct.
  • Regulation: Influenced by the adrenal hormone aldosterone.

pH Regulation by Kidneys

Normal Plasma pH Range
  • pH: 7.35 - 7.45.
Regulation Mechanisms
  • H+ Secretion: Regulates pH by excreting H+ ions into nephron lumen.
  • Bicarbonate (HCO3-) Reabsorption: Involves secreting H+ into the tubule.
Compensation for pH Imbalances
  • Acidosis: Increase H+ secretion, hyperventilate, CO2 removal.
  • Alkalosis: Decrease H+ secretion, reduce CO2 removal.
Diagnosing pH Imbalances
  • Use plasma pH, PCO2, and [HCO3-] for differentiated diagnosis:
    • Respiratory Acidosis: PCO2 > 40 mm Hg, increased H+ secretion by kidneys.
    • Respiratory Alkalosis: PCO2 < 40 mm Hg, decreased H+ secretion by kidneys.
    • Metabolic Acidosis: PCO2 < 40 mm Hg, compensated by respiratory adjustments.
    • Metabolic Alkalosis: PCO2 > 40 mm Hg, kidneys decrease H+ secretion.