Renal Handling of Na+ in PCT

Renal Handling of Na+ in PCT

• 70% of Na+ is reabsorbed in PCT.
• About 70% of Na+ load is reabsorbed in PCT.
• At the luminal border, Na+ is transported from the lumen to inside cells via facilitated diffusion.
• This is impacted by two factors:
  • Concentration gradient
  • Electrical gradient
    • Lumen at -3mV
    • Inside Cell at -70mV
• Large surface area of brush border of PCT & presence of carriers helps this process.
• At the baso-lateral border, Na+ crosses into the interstitium fluid.
• It crosses via active pump against its electrochemical gradient via Na+-K+ ATPase activity.
  • For every 3 Na+ ions pumped out, only 2 K+ ions are carried in.
• After K+ ions enter the cell, they diffuse back into the interstitium due to concentration gradient & cell membrane permeability.
• This maintains intracellular negativity related to luminal fluid which increases Na+ entry into the cell, to help facilitate diffusion.

Reabsorption Results

• 70% of water is reabsorbed, known as "obligatory water reabsorption," due to the high osmolality created by Na+ reabsorption.
• Active co-transport transports glucose, amino acids, HCO3-, & other organic acids using the same carrier as Na+.
• Passive diffusion of Cl- occurs in the 2nd half of PCT due to concentration increase.

Renal Handling of HCO3- in PCT

• More than 99% of HCO3- is reabsorbed by the kidney, especially in the PCT.
• Reabsorption is affected by the acid-base balance.
  • Alkalosis: excretion of HCO3- is increased and, urine becomes alkaline (normal urine is acidic at pH=6)
  • Acidosis: HCO3- reabsorption is complete.
• Renal tubules are poorly permeable to HCO3-, but it undergoes reabsorption as CO2, which is highly permeable.
• Mechanism Steps:
  • Step 1 (intracellular): CO2 from blood & tubular fluid diffuses into PCT cells, CO2 binds with H2O with the help of Carbonic Anhydrase (CA) which results in H2CO3, that then ionizes to HCO3- + H+.
  • Step 2 : H+ is secreted into the lumen, exchanging with Na+ (from filtered NaHCO3) via secondary active transport (Na+/H+ counter-transport) and then Na+ diffuses into blood.
  • Step 3 (intra-luminal): Secreted H+ combines with filtered HCO3- with, the help of CA in the brush border of the PCT cells in order to form H2CO3 which creates H2O & CO2, with CO2 diffusing back into the tubular cells.
  • Step 4: Formed HCO3- inside the cell moves passively through the basal border to the interstitium, binds Na+, and then creates NaHCO3.

Renal Handling of Potassium

• 1.K+ load measures 760/mEq per day.
• 65% is actively reabsorbed by the PCT.

Renal Handling of Calcium

• 99% of filtered Ca2+ is reabsorbed, with 65% of that occurring in the PCT.
• An increase in the rate of Na+ reabsorption will lead to an increase in Ca2+ reabsorption by the PCT.

Renal Handling of Phosphate

• Parathormone inhibits phosphate reabsorption while increasing Ca2+ reabsorption in order to maintain a constant solubility product.

Renal Handling of Glucose

• Glucose serves as the primary fuel source for various body tissues, including brain and cornea.
• It is almost completely reabsorbed by the PCT in the kidney, with only a negligible amount appearing in urine over 24 hours.
• Glucose is reabsorbed through secondary active transport, coupled with Na+ reabsorption.
  • In the 1st half of PCT: a common carrier binds both Na+ and glucose at the luminal brush border where Na+ diffuses from lumen to the inside of the cell with an electro-chemical gradient.
  • Increased glucose concentration within cells leads to the glucose undergoing passive transport from the basolateral border to the interstitium via facilitated diffusion.
• The common carrier for Na+ and glucose at the luminal border is called SGLT2, while the glucose carrier at the basolateral border is called GLUT2.
• Energy required for this transport derives from the energy that is released by Na+ K+ ATPase at the basolateral border of cells.
• The presence of insulin is not critical for glucose transport in PCT cells.

Renal Threshold of Glucose

• Definition: Blood glucose where glucose doesn't appear in urine.
• The blood level of glucose under which glucose never appears in the urine is where it is completely reabsorbed & has a plasma clearance of zero.
• The value for this level is 180mg/dl in a healthy adult.
• When glucose surpasses 180 mg/dl, it begins to appear in the urine, and the kidney's capacity to reabsorb glucose increases due to increased activity in the carrier system.
• With increased hyperglycaemia, there is going to be more glucosuria & a greater increase in kidney capacity for reabsorption of glucose.
• As glucose reaches a particular level, carriers become fully saturated and any excess glucose gets excreted in the urine.
• The point at which it gets excreted is called the maximum transport of glucose.

Tubular Maximum Transport of Glucose(TmG)

• Definition: The level of tubular that determines when any excess glucose is excreted in the urine.
• The value is = 375 mg/min, which corresponds to a plasma level = 300 mg/dl (300 mg/min in females).
• TmG is dependent on:
  • Reabsorptive power of the nephrons: some have reabsorptive power at tubular load of only 200 mg/min, compared to others who have more and more til the all nephrons work by their maximum capacity, in which the TmG level is reached.
  • Carrier system:
    • It binds to the "d" isomer more than "L" isomer of glucose.
    • Competing monosaccharides: galactose, xylose & fructose.

Renal Handling of Urea

• Urea is formed in the liver as an end product of nitro metabolism.
• Normal blood urea level equals 20 - 40 mg/dl.
• Blood urea nitrogen BUN = ½ blood urea = 10-20 mg/dl.
• 40 to 60% of the filtered urea are excreted, the amount varies based on urea concentration in plasma & GFR.
• Minimal amounts of urea are reabsorbed in PCT.

Renal Handling of Uric Acid (UA)

• Uric acid is produced as a product of purine metabolism.
• Filtered UA can then be:
  • Reabsorbed (90%) in the PCT
  • Secreted (10%) in the PCT
  • Excreted in urine (20%)
• Net reabsorption in PCT = 80%.

Renal Handling of Proteins & Amino Acids

• About 1% of albumin is filtered in the kidney but gets fully reabsorbed by pinocytosis.
• Some diseases such as nephritis, will decrease sialoproteins which results in an increase in albumin loss in urine.
• Amino acids undergo renal handling in a similar way to glucose reabsorption: Active in PCT, dependent on Na+ transport & shows tubular maximum due to carrier saturation.

Renal Handling of Water

• 1.5 liters of urine is excreted i.e. 99% of water is reabsorbed from 180 liters of plasma that are filtered/day in both kidneys.
  • A: Water reabsorption in PCT:
    • About 70% of water is reabsorbed in the PCT.
    • This water reabsorption is passive, due to active transport of other solutes (NaCL, glucose & amino acids) creating a high osmotic pressure in the renal interstitium.
    • It is then called obligatory water reabsorption because it operates independent of the ADH effect.
    • The water reabsorption in PCT is assisted by water channels, or Aquaporin-1 in the luminal border of cells.