lect 6 objs

• Lecture on Renal Physiology


  MARCH 5, 2024
• Renal reabsorption of selected solutes and water

  Starts in the proximal convoluted tubule
• Email: [e-mail]
• Water movement depends on aquaporins and the water permeability of tight junctions
• GENERAL PRINCIPLES OF RENAL TRANSPORT:
• Carriers can be saturated, meaning their rate of transport has an upper limit
• Renal epithelial transport is transcellular and paracellular
• Renal glucose transport is commonly used to illustrate Tm
• Lecturer: 'Deborah A. Podolin, PhD'
• The kidneys filter about 180 liters of water each day that contains essential and non-essential substances. They have to reclaim what is essential and excrete what is not.
• Renal tubular cells both reabsorb and secrete solute
• Key functions of each segment of the nephron

  • The solute transporters and ion channels present
  • The distribution and permeability of its water pores, aquaporins
  • The relative “leakiness” of its epithelial tight junctions (TJ’s) to water and solutes
  • The responsiveness of specific carriers, channels and aquaporins to hormonal control
• Basolateral Na+-K+ pumps drive carrier-mediated solute transport by establishing an electrochemical gradient for Na+ entry from the lumen
• Solute transport depends on protein carriers and ion channels, their distribution along the nephron and location in the basolateral or apical cell membrane
• The Tm or “transport maximum” for a given substance is the rate of transport when the carriers are saturated
• Substance with Tm

  • Renal glucose transport
• As plasma glucose level increases, so does the amount of glucose in urine. When plasma glucose reaches 350-400 mg/dl, rate of glucose reabsorption becomes constant at Tm. Glucose filtered above Tm is not reabsorbed and is excreted
• Saturation in transport


  Rate of transport has an upper limit
• At normal blood sugar levels, the proximal tubule reabsorbs all filtered glucose co-transported with Na+. Tm for glucose transport is about 375 mg/min
• PT reabsorption


  Filtered Na+ and water (70%), HCO3- (80%), PO4-3 (80%), Ca2+ (2/3), essential nutrients like glucose and amino acids, organic acids, short peptides, and other substances
• PT reabsorbs solutes and water through and between cells, with isosmolar reabsorption due to highly permeable tight junctions
• Paracellular solute and water reabsorption in the PT

  Na+ and other solutes accumulate in the interstitium creating a concentration gradient for water to move into the interstitium seeking osmotic equilibrium, dragging other solutes with it (solvent drag)
• Na+ cotransport in the PT

  Glucose, phosphate, amino acids, sulfates, lactate, mono- and di-carboxylic acids
• PT secretion


  Organic ions including drugs and toxins, synthesis and secretion of ammonia for H+ excretion and new HCO3- generation
• Glucose starts to appear in urine at a blood level of 180-200 mg/dl, below the concentration that would saturate the transporters. More glucose filtered leads to saturation of SGLTs near Bowman’s space
• Proximal Convoluted Tubules (PT) are high capacity, handling large volumes of water and solute
• Tm or "transport maximum"


  Rate of transport when carriers are saturated
• Glucose-Na+ cotransporters

  • SGLT-1 and -2
• Renal reabsorption of Na+

  Integral to maintenance of extracellular fluid volume, with >99% of filtered Na+ normally reabsorbed
• Na+ counter-transport in the PT

  Uses a Na+-H+ exchanger
• Corticomedullary concentration gradient

  • Generated by the loops of Henle
  • Maintained by the vasa recta
• Countercurrent Multiplication

  Countercurrent multiplication can be thought of in two steps: The single effect and Fluid flow
• Lecturer: 'Deborah A. Podolin, PhD'
• Urea comprises about half of the solute in the deep renal medullary interstitium. Urea is important for urinary concentration and dilution processes.
• Renal Physiology


  MARCH 5, 2024
• Email: [e-mail]
• The solute concentration in the renal interstitium increases from the cortex to the medulla
• Loop of Henle process

  The TAL transports NaCl to the interstitium. No water follows. 2. Water leaves the thin descending limb. 3. The fluid flows. 4. Repeat.
• Reabsorption of solutes and water in the kidney

  1. Water drags other solute with it, known as solvent drag

  2. Bulk, passive reabsorption where whatever is in the filtrate that could cross the tight junctions can be dragged across with the water

  3. Reabsorbed solutes and water enter the peritubular capillaries driven by Starling forces

  4. If a concentration gradient for any given solute increases during its movement down the tubule, paracellular solute transport of that solute is enhanced
• Reabsorption of filtered Cl-

  1. Majority of PT Cl- reabsorption is paracellular

  2. Cl- reabsorption in the late PT is both cellular and paracellular

  3. Paracellular Cl- reabsorption lags behind Na+, HCO3-, and water transport in the early PT

  4. Final segment of the PT has chloride transporters for Cl- reabsorption