[OS 206] E03-T07-Tubular Secretion and Renal Regulation of Electrolytes_compressed

• Tubular secretion and the renal regulation of electrolytes are key to kidney function.
• Learning objectives include reviewing transport mechanisms in the renal tubule and discussing the renal handling and secretion of different solutes.

Tubular Secretion

• Tubular secretion involves the transfer of materials from the blood and tubule cells into the glomerular filtrate.
• It aids in the elimination of waste from the body, including drugs and waste products.
• Main focuses of secretion include K+, H+/HCO3, PO4, NH4+/urea, creatinine, and certain substances like EPO, steroids, and HCG.
• Thick segments of the tubule are water impermeable, while thin segments are water permeable.

Nephron Segments and Function

• Nephron parts include the glomerulus, proximal tubule, Loop of Henle, distal tubule, and collecting duct.
• Glomerulus is responsible for filtration of plasma.
• Proximal tubule reabsorbs nutrients and bicarbonate.
• Loop of Henle concentrates urine.
• Distal tubule fine-tunes electrolytes.
• Collecting duct balances water and urea.

Glomerulus Structure

• Glomerulus includes the Bowman's capsule, glomerular space, afferent arteriole, efferent arteriole, and podocytes.
• Podocytes surround the capillaries.
• Kidney glomeruli act as strainers involved in filtration.
• Urinalysis showing all types of cells indicates a glomerular problem, potentially impairing blood filtration.

Kidney Tubule Details

• Tubules regulate reabsorption and secretion.
• Secretion eliminates waste and involves removing drugs and waste products into the urinary space.
• Focus areas include K+, regulation of blood pH via H+/HCO3, PO4, NH4+/urea, creatinine, drugs, and certain detectable substances in urine.
• Proximal Convoluted Tubule (PCT) has the highest percentage of reabsorption, associated with various transporters for glucose, amino acids, HCO₃, urea, uric acid, and bilirubin.
• Loop of Henle concentrates urine using a countercurrent multiplier.
• Thin descending Loop of Henle is permeable to water because of Aquaporin-1 (AQP1) channels but impermeable to Na+, Cl-, and urea.
• Thick ascending Loop of Henle actively reabsorbs Na+, K+, and Cl via the Na+-K+-2Cl cotransporter (NaKCC), which is inhibited by furosemide.
• Distal Convoluted Tubule (DCT) corrects pH and electrolytes, reabsorbing H+, Ca2+, Mg2+, and Na2+ via the Na+-Cl co-transporter (NCC), which is inhibited by thiazide.
• Cortical Collecting Duct is important for final urea and water balance.
• It is associated with urea recycling and regulation by aldosterone (Na+ reabsorption and K+ excretion) and antidiuretic hormone (ADH, water reabsorption via AQP2).

Reabsorption and Secretion Summary

• Proximal Tubule secretes H+, NH4+, Urea, Creatinine.
• Late Distal Tubule and Collecting Duct handle K+ and H+.

Urinalysis Significance

• Urinalysis offers key insights into kidney function, with different nephron segments influencing urine composition.
• Key parameters include color, clarity, microscopic findings (casts, cells, crystals), pH, specific gravity, proteinuria, hematuria, glucose, and ketones.
• Table 1 shows common urinalysis correlations associated with nephron segments, such as proteinuria indicating glomerulus issues and glycosuria or amino aciduria correlating with proximal convoluted tubule problems.

General Orientation Principle

• Tubules are selective; identify the urinary and blood side.
• Urinary side includes the tubular lumen and urinary space.
• Blood side is the interstitial side/interstitium
• Na+-K+ ATPase pump indicates the basolateral side (blood side).

Active and Passive Transport

• Active transport moves solutes against an electrochemical gradient, requiring energy derived from metabolism
• Primary active transport is directly coupled to an energy source (e.g., ATP hydrolysis).
• Secondary active transport is indirectly coupled to an energy source, relying on an ion gradient, and is aided by the Na+-K+ ATPase pump.
• Passive transport, such as osmosis, is coupled mainly to sodium reabsorption.

Tubular Segment Reabsorption

• Proximal Convoluted Tubule (PCT):
  • All substances are reabsorbed with sodium.
  • Sodium cotransports glucose, amino acids, and other solutes.
  • Involved in acid-base regulation, excreting H+ in acidic conditions.
• Loop of Henle:
  • Important in urine concentration.
    • Thin descending segment highly permeable to water.
    • Thick ascending segment actively reabsorbs sodium, chloride, potassium, calcium, magnesium, and bicarbonate.
• Distal Convoluted Tubule (DCT): Used for pH and electrolyte correction, reabsorbing H+, Ca2+, Mg2+, and Na2+.
• Cortical Collecting Duct: Balances urea and water.
  • Regulated by:
    • Aldosterone: Increases Na+ reabsorption and K+ excretion.
    • Anti-diuretic hormone (ADH): Promotes water reabsorption.

Kidney Excretion of H+

• Production of nonvolatile acid is 1 mEq H+/kg body weight per day.
• Excreted via the kidneys primarily in PCT cells and intercalated cells (of DCT & collecting duct).
• deamination and metabolism of glutamine and glutamate produces ammonia (NH3) and bicarbonate (HCO3-).
  • excess NH3 = diffuses into the tubular lumen
  • combines with filtered H+ ion (from HCO3- reabsorption) to form NH4+ (Ammonium).
  • NH4+ is trapped in the tubular lumen and carries excess H+ excreted into urine.

Renal Potassium Handling

• Most potassium is intracellular, maintained by the Na+-K+ ATPase pump.
• Extracellular K+ concentration is tightly regulated due to its effect on cell functions, especially cardiac stability.
• Factors shifting K+ into cells (decreasing extracellular [K+]) include insulin, aldosterone, β-adrenergic stimulation, and alkalosis
• Factors shifting K+ out of cells (increasing extracellular [K+]) include insulin deficiency, aldosterone deficiency, β-adrenergic blockade, acidosis, cell lysis, strenuous exercise, and increased extracellular fluid osmolarity.
• High K+ intake stimulates aldosterone secretion, influencing K+ uptake into cells.
• Increased hydrogen ion concentration reduces Na+-K+ ATPase pump activity, decreasing cellular potassium uptake.
• Alterations in ECF osmolarity cause water to flow in/out of cells, affecting intracellular K+ concentrations and subsequent movement of K+ driven by diffusion.
• Intercalated cells handle acid-base balance and are connected to potassium handling
• Aldosterone increases potassium excretion

Explore tubular secretion and renal electrolyte regulation. Key topics include the transfer of materials into the glomerular filtrate and the handling of solutes. Learn about nephron segments and their functions, including the glomerulus, proximal tubule, and Loop of Henle.