Dr. imrana ehsan

What do the kidneys do? The glomeruli “non-discriminantly” filter the blood, and the tubules take back what the body needs leaving the rest as waste to be excreted. Some wastes also can be actively added to the tubular fluid.

 Amount filtered= GFR*Plasma concentrates  Excretion refers to the removal of solutes and water from the body in urine  Reabsorption (movement from tubular fluid to peritubular blood) and secretion (movement from peritubular blood to tubular fluid) refer to direction of movement of solutes and water across the renal tubular epithelium

 The luminal cell membranes are those that face the tubular lumen (“urine” side)  The basolateral cell membranes are those are in contact with the lateral intercellular spaces and peritubular interstitium (“blood” side)  Tubular reabsorption is highly selective.  Small changes in GFR produces large changes in excretion rates.

 The transmembrane potential difference is the electrical potential difference between the inside and outside of the cell  The transepithelial potential difference is the electrical potential difference between the tubular lumen and the peritubular interstitium

 The term transcellular refers to movement of solutes and water through cells  The term paracellular refers to movement of solutes and water between cells  Epithelial cell junctions can be “leaky” (proximal tubule) or “tight” (distal convoluted tubule, collecting duct)

Terminology Transepithelial versus transmembrane potential difference Luminal versus basolateral membranes Transcellular versus paracellular transport

 Leaky epithelia (proximal)  Small transepithelial concentration difference  Small TEPD  High water permeability  Tight epithelial (distal)  Large transepithelial concentration difference  Large TEPD  Low water permeability

That renal tubular reabsorption must occur is intuitively obvious because … The fluid filtered into Bowman’s space is an ultrafiltrate of plasma containing many vital small molecular weight solutes (e.g., glucose, amino acids, bicarbonate) but these solutes do not normally appear in urine

 Solute reaborption in the proximal tubule is isosmotic (water follows solute osmotically and tubular fluid osmolality remains similar to that of plasma)  65% of water and solute reabsorption occurs in the proximal tubule  90% of bicarbonate  99% of glucose & amino acids  Proximal tubules: coarse adjustment  Distal tubules: fine adjustment

Cl - goes up because Na + is reabsorbed with glucose, amino acids, P i and HCO 3 - Glucose, amino acids, P i and HCO 3 - go down due to reabsorption with Na + Unchanged due to isosmotic reabsorption

LUMINAL BASOLATERAL Glucose, P i amino acids Na + H+H+H+H+ 3 Na + 2 K + K+K+K+K+ HCO H 2 CO 3

 Passive transport (simple diffusion)  Facilitated diffusion  Primary active transport  Secondary active transport  Pinocytosis  Solvent drag

 Movement of a substance across a membrane as a result of random molecular motion

 No metabolic energy required  Rate of transfer dependent on electrochemical gradient across membrane and membrane permeability characteristics  Rate of transfer linearly related to concentration of diffusion substance (no V max )

 Movement of a substance across a membrane down its electrochemical gradient after binding with a specific carrier protein in the membrane

 Saturable (has a V max )  Structural specificity and affinity of carrier for substance transported  Transfer may occur in either direction across membrane  Does not directly require metabolic energy

 Glucose, amino acids: Basolateral membranes of proximal tubules  Sodium: luminal membranes of proximal tubules

 Movement of a substance across a membrane in combination with a carrier protein but against an electrochemical gradient

 Directly requires metabolic energy (i.e. hydrolysis of ATP)  Saturable (has a V max )  Structural specificity and affinity of the carrier for the substance transported

 Na + -K + ATPase  H + ATPase  H + -K + ATPase  Ca +2 ATPase

 Two substances interact with one specific carrier in the cell membrane and both substances are translocated across the membrane  Co-transport Transported substances move in the same direction across the membrane  Counter-transport Transported substances move in opposite directions across the membrane

 “Uphill” transport of one substance is linked to “downhill” transport of another substance  Carrier must be occupied by both substances (or be unoccupied) to be mobile in the membrane  Saturable (has a V max )  Demonstrates specificity and affinity of carrier for substance transported  “Uphill” transport occurs without direct input of metabolic energy

 Glucose, amino acids, or phosphate with sodium in luminal membranes of proximal tubules  Sodium and hydrogen ions in luminal membranes of proximal tubules

 The metabolic energy for secondary active transport of Na + at the luminal membrane in the proximal tubule comes from Na + -K + ATPase which transports Na + out of the cell across the basolateral membrane and maintains a favorable electrochemical gradient for the entry of Na + at the luminal membrane

LUMINAL BASOLATERAL Glucose, P i amino acids Na + H+H+H+H+ 3 Na + 2 K + K+K+K+K+ HCO H 2 CO 3

 Definition: Uptake by cells of particles too large to diffuse through the cell membrane  Example: Reabsorption of filtered proteins in the proximal tubules

 A solvent such as water moving across an epithelium by osmosis can drag dissolved solutes with it

 Large surface area for reabsorption of water and solutes (brush border, lateral cellular interdigitations)  Large numbers of mitochondria to provide ATP  Leaky epithelial junctions  Loaded with carrier protiens.

 Paracellular  1% of surface area  5-10% of water transfer  Passive diffusion or solvent drag only  Requires favorable electrochemical gradient  Passive diffusion of ions and large non-polar solutes  Transcellular  99% of surface area  90-95% of water transfer  Passive or active transport  All active transport occurs by this route

 PROXIMAL HALF;sodium, water, bicarbonate, amino acids, glucose, and phosphate reabsorbed  DISTAL HALF:sodium, water and chloride reabsorption.  Secretes hydrogen ions,organic acids and bases like bile salts,oxalate,urate and catecholamines.  Secrete toxins and drugs  Secretes PAH.

 Glucose, Amino acids  T max high and constant (kidney not a regulator of plasma glucose and amino acid concentrations)  Phosphate  T max low and altered by PTH (kidney is a regulator of plasma phosphtate concentration)

 In renal tubular cells found only in basolateral membrane  When ATP is hydrolyzed, 2 K + ions are pumped into the cell and 3 Na + ions are pumped out  Maintains favorable electrochemical gradient for Na + entry at luminal membrane  Maintains cell membrane potential difference and intracellular osmolality

 Endocytosis: Filtered proteins adsorbed to sites on luminal membranes that are internalized to form endosomes. Fusion with lysosomes forms endolysosomes in which digestion of proteins occurs  Hydrolysis of filtered proteins to constituent amino acids by enzymes in brush border of proximal tubular cells

 Urea is passively reabsorbed in the proximal tubule  More urea is reabsorbed at low tubular flow rates than at high tubular flow rates  Contributes to BUN increasing out of proportion to creatinine in dehydrated patients even before GFR decreases