DV

Renal Physiology Notes

Proximal Tubule (PT) Reabsorption

  • Sodium Reabsorption
    • Basolateral side: Active transport
    • Apical side: Variety of symport, antiport, or leak channels
  • Sodium-linked active reabsorption
    • NaHCO3 and Na-organic solutes are primarily reabsorbed in the first half.
    • Co-transport with glucose, amino acids, organic solutes.
    • Counter-transport with H+ ions
  • Passive Reabsorption: Urea
    • No active transporters in the PT.
    • Passive reabsorption due to urea concentration gradient.
    • Transcellular and paracellular pathways.
  • Transcytosis: Protein
    • Small proteins and peptides can pass through the filtration barrier.
    • Most filtered proteins are removed from filtrate in the PT.
    • Receptor-mediated endocytosis - renal digestion terminates peptide signal.
  • Fanconi's Syndrome
    • Impaired ability of the proximal tubule can lead to increased levels of the following substances in the urine:
      • HCO3-
      • Amino acids
      • Glucose
      • Low molecular-weight proteins

Proximal Tubule Secretion

  • H+
    • Apical Na-H+ exchanger (NHE).
  • Ammonium ions
    • Na-NH4+ antiport
  • Process
    1. Na+-H+ antiport secretes H+.
    2. H+ in filtrate combines with filtered HCO3- to form CO2.
    3. CO2 diffuses into the cell and combines with water to form H+ and HCO3-.
    4. H+ is secreted again and excreted.
    5. HCO3 is reabsorbed.
    6. Glutamine is metabolized to ammonium ion and HCO3-.
    7. NH4+ is secreted and excreted.
    8. HCO3 is reabsorbed.

Organic Compounds

  • Transported across the tubule epithelium primarily by secondary and tertiary active transport.
  • Broad specificity.
  • Organic anions: Bile salts, Urate, Vitamins (ascorbate, folate), PAH, penicillin, toxic chemicals.
  • Organic cations: Creatinine, dopamine, Epinephrine, Atropine, Morphine, Cimetidine, Isoproterenol, procainamide.
  • Drug Interaction Example
    • Taking Cimetidine (a Histamine H2 antagonist) and Procainamide (an antiarrhythmic medicine) simultaneously can lead to drug interactions due to competition for the same transporters.

Clearance of Penicillin

  • The clearance of penicillin is larger than the GFR because it is actively secreted in the proximal tubule.

Loop of Henle Reabsorption

  • 30% of the filtrate reaches here.
  • Reabsorbs:
    • 15% of the filtered water
    • 25% of the filtered NaCl
  • The two parallel segments of the LH have very different permeability to different solutes:
    • Thin descending: permeable to water, moderate to urea, ions.
    • Thin ascending: impermeable to water but permeable ions (solutes).
    • Thick ascending: impermeable to water and ions but actively pumps out Na+/Cl-
  • Osmolarity changes:
    • 1200 mOsm/L at the bottom.
    • 300 mOsm/L at the top.

Distal Tubule and Collecting Duct

  • Reabsorption
    • Na+, Cl- (Aldosterone sensitive)
    • Water (ADH sensitive)
  • Secretion
    • K+ (Aldosterone sensitive)
    • H+ (pH dependent)
    • NH4+ ion, organic ions, creatinine, penicillin
  • Ion Exchange
    • K+ is exchanged for Na+.
    • H+ is exchanged for K+.
  • Caution
    • Taking a medication that inhibits Na+ channels to treat hypertension may cause electrolyte imbalances, affecting K+ and H+ levels.

Acidosis and Alkalosis

  • Acidosis (Type A Intercalated Cells)
    • Occurs when [H+] is high.
    • H2O + CO2 converts to HCO3- + H+ via carbonic anhydrase (CA).
    • Excretes H+ and reabsorbs K+.
    • HCO3- acts as a Cl- buffer.
  • Alkalosis (Type B Intercalated Cells)
    • Occurs when [H+] is low.
    • H2O + CO2 converts to HCO3- + H+ via carbonic anhydrase (CA).
    • Excretes K+ and HCO3-.

Effect of Plasma pH on Potassium in Urine

  • A decrease in pH in plasma would lead to a decrease in the amount of potassium in the urine because the kidneys will reabsorb more potassium to excrete more H+.

ADH Sensitive Water Reabsorption

  • ADH (Vasopressin) causes insertion of water pores (Aquaporin-2) into the apical membrane.
  • Stimuli for ADH Release
    • Osmolarity greater than 280 mOsM
    • Decreased atrial stretch due to low blood volume
    • Decreased blood pressure
  • Mechanism
    1. Vasopressin binds to membrane receptor.
    2. Receptor activates cAMP second messenger system.
    3. Vesicles with AQP2 water pores are inserted into the apical membrane.
    4. Water is absorbed by osmosis into the blood.
  • Systemic Response
    • Increased water reabsorption to conserve water

Clinical Correlation: Desert Trip Scenario

  • Scenario: Two men, A and B, are driving through the desert.
    • A drinks beer in the tavern (Excessive uptake of fluids & Hydration).
    • B hikes into the desert (Excessive sweating & Dehydration).
  • Effects: The table was not fully filled, so I can't completely explain, but it discusses the impact on things like blood osmolarity, ADH secretion, insertion/removal of water channels, water reabsorption, and urine volume.

Aldosterone Sensitive Sodium Reabsorption

  • Negative Sodium Balance: Aldosterone is released when:
    • Decreased Blood Pressure (through renin-ANG II)
    • Increased extracellular K+ concentration

Aldosterone and Potassium

  • Increased extracellular [K+] stimulates Aldosterone secretion to prevent hyperkalemia.
    • Hyperkalemia can lead to cardiac arrhythmias.
  • Reflex Loop
    • Increased plasma [K+] leads to increased Aldosterone.
    • Increased Aldosterone leads to increased tubular secretion of K+ (in exchange for Na+).

Renal Physiology Outline

  • The Kidneys:
    • Anatomy of the urinary system.
    • Overview of renal processes.
  • Filtration:
    • GFR Regulation.
    • Calculate glomerular filtration rate.
    • Calculate renal blood flow.
  • Absorption, secretion, and excretion:
    • Calculate renal threshold for a substance.
  • Fluid and Electrolyte Balance:
    • Urine Concentration.
    • Water, sodium, potassium, and pH balance.

How Urine is Concentrated

  • Medullary osmotic gradient - established/maintained by juxtamedullary nephrons and vasa recta.
  • Collecting ducts can exploit this gradient to form a concentrated urine.
  • Gradient range: 300 mOsm to 1200 mOsm

Questions

  • At the end of PCT, would you see similar ion concentrations as those at the beginning of PCT?
  • What is the most concentrated urine you would expect to excrete?

How is an Osmotic Gradient Established?

  • Countercurrent Multiplier
  • Key Contributing Factors:
    1. Ascending limb actively transports NaCl, and impermeable to water.
    2. Descending limb (loop of Henle) permeable to water, impermeable to solutes.
    3. Papillary duct permeable to urea (contributes to gradient).

Countercurrent Multiplier Model

  • Illustrates how the osmotic gradient is established through the interaction of the descending and ascending limbs of the loop of Henle.
  • Steps include:
    • Active transport of NaCl from the ascending limb into the interstitium.
    • Water movement out of the descending limb due to the osmotic gradient.
    • Recirculation of urea to contribute to the gradient.
    • The numbers provided in the graphic show how the osmolarity changes in the different parts of the loop over several steps to concentrate the gradient.

Countercurrent Exchanger Mechanism

  • Vasa recta act as a countercurrent exchanger - Maintains osmotic gradient while delivering blood.
  • Blood flow downward: Salt in and water out.
  • Blood flow upward: Salt out and water in.
  • Function: Maintain steep concentration gradient!