Renal Physiology Lectures 5-7

Renal Physiology Lectures 5-7

• Tubular Reabsorption Objectives:
  • Explain sodium reabsorption and the function of Na/K ATPase.
  • Describe the mechanism of water, urea, and chloride reabsorption in the proximal tubule.
  • Explain the reabsorption of peptides and small molecular weight proteins in the proximal tubules.
  • Clinical correlation-Proteinuria.

Trans-epithelial Transport

• Substances must cross five barriers to be reabsorbed from filtrate to plasma:

  • Luminal cell membrane
  • Cytosol
  • Basolateral cell membrane
  • Interstitial fluid
  • Capillary wall

• Steps of Trans-epithelial Transport:

  • Step 1: Substance leaves tubular fluid by crossing the luminal membrane.
  • Step 2: Substance passes through the cytosol from one side of the tubular cell to another.
  • Step 3: Substance crosses the basolateral membrane to enter the interstitial fluid.
  • Step 4: Substance diffuses through the interstitial fluid.
  • Step 5: Substance diffuses through the capillary wall to enter the blood.

Sodium Reabsorption by Various Nephron Parts

• 65% of sodium is reabsorbed in the proximal tubule, 25% in the loop of Henle, and 4-8% in the distal and collecting tubule.
• Proximal tubule reabsorption is crucial for glucose, amino acids, water, chloride, and urea.
• Loop of Henle reabsorption plays a role in producing urine with varying concentrations.
• Distal and collecting tubule reabsorption is variable and controlled by hormones, crucial for regulating ECF volume and arterial blood.

Active Na-K ATPase Pump

• 80% of the kidney's energy is spent running the Na-K ATPase pump.
• The pump actively extrudes Na from the cell, building up Na concentration in the lateral space.
• This creates a concentration gradient that facilitates passive Na movement from the tubular lumen into the tubular cell.
• Sodium continues to diffuse down a concentration gradient from the lateral space to the interstitial fluid.

Active Na Reabsorption Responsible for Passive Reabsorption

• Water is passively reabsorbed throughout the tubule, following Na.
• Approximately 65-117 liters of filtered water per day is passively reabsorbed by the end of the proximal tubule.
• Reabsorption primarily occurs via aquaporin 1 water channels.
• The return of filtered water to plasma is enhanced by higher osmotic pressure in peritubular capillaries.

Active Na Reabsorption for Urea Reabsorption

• Urea reabsorption at the glomerulus is identical to its concentration in the entering peritubular capillaries.
• Osmotically induced water reabsorption, secondary to active Na reabsorption, creates a concentration gradient for passive urea reabsorption.
• Only approximately 50% of filtered urea is passively reabsorbed.

Reabsorption of Filtered Peptides by the Proximal Tubule

• Substances with approximately 10 kDa are freely filtered at the glomerulus.
• Molecular weight increases cause a decline in filtered solute amounts.
• The proximal tubule actively reabsorbs filtered peptides and low-molecular-weight proteins.
• Proteins are broken down into amino acids and reabsorbed via co-transport with Na.

Reabsorption of Low Molecular Weight Proteins

• Low-molecular-weight filtered proteins (insulin, glucagon, parathyroid hormone) are absorbed via receptor-mediated endocytosis.
• These proteins bind to receptors (megalin, cubilin) in the plasma membrane, leading to endocytosis.
• Endocytosed proteins are delivered to lysosomes for degradation and recycling.

Clinical Correlation: Proteinuria

• Proteinuria can be categorized as normal, overflow, glomerular, or tubular.

Objectives for Renal Physiology

• Glucose reabsorption in the proximal tubule.
• Sodium and potassium handling in the loop of Henle, distal convoluted tubules, and collecting tubules.
• Mechanism of action of aldosterone.
• Potassium handling in different parts of the nephron.
• Aldosterone-clinical correlation (Hypoadrenocorticism).
• Aldosterone antagonists as diuretics.

Glucose Reabsorption in Proximal Tubules

• Glucose is reabsorbed via Na-dependent secondary active transport.
• Sodium and glucose are simultaneously transported into the cell by SGLT.
• A limited number of SGLT molecules limits the maximum amount of glucose that can be actively transported.

Mechanisms of Sodium, Chloride, and Potassium Transport in the Thick Ascending Loop of Henle

• The sodium-potassium ATPase pump maintains low intracellular sodium concentration.
• The 1-sodium, 2-chloride, 1-potassium co-transporter moves these ions from the tubular lumen into the cells.
• Energy from sodium diffusion creates the driving force for transport.

Mechanism of Sodium Chloride Transport in the Early Distal Tubule

• The sodium-potassium ATPase pump in the basolateral membrane maintains low intracellular sodium concentration.
• The sodium-chloride co-transporter moves sodium and chloride from the tubular lumen into the cells.
• Chloride diffuses out of the cell through chloride channels in the basolateral membrane and into the renal interstitial fluid.

Diuretics

• Various diuretics (loop, thiazide, K+-sparing, carbonic anhydrase inhibitors) have different mechanisms of action that influence sodium and water reabsorption in the kidney.

Activation of the Renin-Angiotensin-Aldosterone System

• Granular cells function as intrarenal baroreceptors.
• Decreased NaCl triggers macula densa cells to stimulate renin secretion.
• Increased sympathetic activity also stimulates renin secretion.

Regulation of Na Reabsorption and Potassium Ion Secretion

• Na/K ATPase pump moves Na out of the cell and transports K from the lateral space into the principal cells of CT. This process enables high intracellular K concentration, facilitating passive K movement into the tubular lumen via leak channels.
• K is then moved out of the peritubular capillary plasma into the interstitial fluid.

Mechanism of Action of Aldosterone

• Acute Effects: Promotes Na+ reabsorption and K+ secretion via stimulating Na+/K+-ATPase activity and increasing open probability of Na+ channels (ENaC).
• Chronic Effects: Increases Na+/K+-ATPase abundance, expression of NaCl co-transporter (NCC) in the distal convoluted tubule and ENaC in collecting duct principal cells.

Summary of Na Handling by the Kidney

• Kidneys adjust salt excretion by regulating GFR and Na reabsorption.
• Na reabsorption in the distal and collecting tubules is a function of the renin-angiotensin-aldosterone system.
• The RAAS promotes Na retention by stimulating Na reabsorption. Amount of filtered Na is controlled by GFR and amount of salt excreted by two processes.

Distribution of Potassium in Body Compartments

• Potassium is primarily intracellular (98%), with small amounts in the extracellular fluid.
• Small changes in extracellular K concentrations can significantly impact the body's membrane electrical activity (excitable tissues).

Potassium Handling by the Kidney

• Potassium is actively reabsorbed in the proximal tubule and loop of Henle, and primarily secreted in the distal and collecting tubules.
• Potassium secretion is controlled by the principal cells and other cells.
• Potassium secretion in distal parts is important to maintaining a balance of K concentrations in the body.

Regulation of Potassium Secretion

• Several factors alter the rate of K secretion, with aldosterone being the most influential.
• Elevation in systemic potassium stimulates the adrenal cortex to release more aldosterone. Increased aldosterone causes increased K secretion and Na reabsorption.

Aldosterone Functions in the Kidney

• Aldosterone affects principal cells of the collecting ducts by increasing Na reabsorption and promoting K secretion.
• Aldosterone stimulates hydrogen secretion in intercalated cells of the collecting ducts. Both of these processes contribute to electrolyte and acid-base balance.

Hypoadrenocorticism (Addison's Disease)

• Aldosterone deficiency is a key characteristic.
• Other symptoms include hyperkalemia, hyponatremia, hypochloremia and metabolic acidosis, polyuria, polydipsia, weakness, recurrent vomiting, and diarrhea.

Quiz Questions (Examples)

• (various quiz questions about specific cases and conditions.)