Renal Tubular Reabsorption Dr imrana ehsan What do

Renal Tubular Reabsorption 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.

Renal tubular reabsorption: (URINARY EXCRETION=GF- tubular reabsorption+tubular secretion) � � � 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

Renal tubular reabsorption � � 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.

Renal tubular reabsorption 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

Renal tubular reabsorption 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

Renal tubular reabsorption Leaky epithelia (proximal) Small transepithelial concentration difference Small TEPD High water permeability Tight epithelial (distal) Large transepithelial concentration difference Large TEPD Low water permeability

Renal tubular reabsorption 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

Renal tubular reabsorption 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, Pi and HCO 3 Unchanged due to isosmotic reabsorption Glucose, amino acids, Pi and HCO 3 - go down due to reabsorption with Na+

Secondary active co-transport (glucose, amino acids, phosphate) LUMINAL Glucose, Pi amino acids Na+ HCO 3 - Na+ + H+ H 2 CO 3 BASOLATERAL 2 K+ 3 Na+ K+

Types of transport processes Passive transport (simple diffusion) Facilitated diffusion Primary active transport Secondary active transport Pinocytosis Solvent drag

Passive transport (simple diffusion): Definition Movement of a substance across a membrane as a result of random molecular motion

Passive transport (simple diffusion): Characteristics 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 Vmax)

Facilitated diffusion: Definition Movement of a substance across a membrane down its electrochemical gradient after binding with a specific carrier protein in the membrane

Facilitated diffusion: Characteristics Saturable (has a Vmax) � Structural specificity and affinity of carrier for substance transported � Transfer may occur in either direction across membrane � Does not directly require metabolic energy �

Facilitated diffusion: Examples Glucose, amino acids: Basolateral membranes of proximal tubules Sodium: luminal membranes of proximal tubules

Primary active transport: Definition Movement of a substance across a membrane in combination with a carrier protein but against an electrochemical gradient

Primary active transport: Characteristics Directly requires metabolic energy (i. e. hydrolysis of ATP) Saturable (has a Vmax) Structural specificity and affinity of the carrier for the substance transported

Primary active transport: Examples Na+-K+ ATPase H+-K+ ATPase Ca+2 ATPase

Secondary active transport: Definition 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

Secondary active transport: Characteristics “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 Vmax) Demonstrates specificity and affinity of carrier for substance transported “Uphill” transport occurs without direct input of metabolic energy

Secondary active transport: Examples Glucose, amino acids, or phosphate with sodium in luminal membranes of proximal tubules Sodium and hydrogen ions in luminal membranes of proximal tubules

Secondary active transport 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

Secondary active co-transport (glucose, amino acids, phosphate) LUMINAL Glucose, Pi amino acids Na+ HCO 3 - Na+ + H+ H 2 CO 3 BASOLATERAL 2 K+ 3 Na+ K+

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

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

Morphologic features of proximal tubular cells � � 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.

Routes of transport across proximal tubular epithelium 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

Intrasegmental axial heterogeneity of proximal tubule � � � 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.

Secondary active transport Glucose, Amino acids Tmax high and constant (kidney not a regulator of plasma glucose and amino acid concentrations) Phosphate Tmax low and altered by PTH (kidney is a regulator of plasma phosphtate concentration)

Secondary active transport: Glucose

Secondary active transport: Phosphate

Na+-K+ ATPase 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

Pinocytosis 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: Passive diffusion 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