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Flashcards in Sriramula Deck (37)
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Major sites of Sodium Reabsorption

  • Proximal Tubule
    • 65-70%
  • Ascending limb of loop of Henle
    • 20-25%
  • Distal Tubule
    • 5%
  • Collecting duct
    • 1-5%
  • Where sodium goes, water goes
  • Less than 1% of the filtered sodium load is excreted per day



  • Kidneys always want to preserve at the expense of other electrolytes 
    • even K+
  • Water follows
  • <1% of filtered sodium load exreted per day


What controls renal function

  • Renin Angiotensin Aldosterone System
  • Renal Nerves/catecholamines
  • Renal pressure gradient
    • perfusion pressure
    • Interstitial pressure
  • Vasopressin (ADH)
  • Autocoids
    • prostaglandins
    • Nitric Oxide
    • Bradykinin


What is the function of the kidneys

  • Fluid and electrolyte homeostasis
  • BP control
  • Detoxification


What electrolyte is preferentially absorbed by the kidneys?

Sodium at the expense of other electrolyes

even K+


What is the role of the afferent and efferent arteriole

  • Differential resistance buiilt in these 2 vascular beds
  • blood will be forced to stay in the capsule
  • glomerular filtration
    • changes in GFR=constriction/dilation of afferent/efferent


What regulate afferent and efferent arteirole tone



Why is renin important with renal artery stenosis

  • Upregulation of intra-renal renin-angiotensin system maintains GFR in renal artery stenosis patients
  • vasoconstricts efferent arterioles


What drugs would lead to renal failure with renal arter stenosis

  • ACEIs or ARBs leads to kidney failure.



  • Inhibit electrolyte reabsorption in the kidney
  • increase rate of urine flow


What are the primary and secondary effects of diuretics

  • Primary
    • increase solute excretion
      • mainly Na+
  • Secondary effect
    • increase urine flow
      • response to the osmotic force of solutes within the renal tubule lumen


Different types of Diuretics and major site of action


Epithelial Transporters

  • Channels
    • Na, K, Cl
  • Antiporter/Countertransport
    • Na-K ATPase
    • Na-H Exchanger
  • Sympoter/Cotransport
    • Na-Cl
    • Na-K-2Cl


Osmotic DIuretics

  • Prototype=Mannitol
    • no molecular target
  • interfer directly with osmosis
  • Major site of action=Proximal tubule


Osmotic Diuretic Characteristics

  • Free Glomerular Filtration
  • Limited or no tubular reabsorption
  • Pharmacologically inert
    • minor side effects/DDI


What is the prototypical osmotic drug



How do osmotic diuretics work?

interfere directly with osmosis


What is the major site of action of osmotic diuretics

  • Proximal tubule


What is the MOA of mannitol

  • Water moves across the membrane from low osmolarity (dilute side) to higher osmoloarity (Concentrated side)
  • Mannitol:
    • Loss of water
    • Reduced intracellular volume
    • Hypernatremic risk 


Osmotic Diuretics: Therapeutic uses

  • acute renal failure (hypovolemic shock/trauma)

    • Prophylactic diuresis 

    • maintains urine flow

  • Cerebral edema (Mannitol I/V infusion

    • raises osmotic pressure

      •  water moves from brain to general circulation)

  • Glaucoma

    • preoperatively

    • reduce intraocular pressure before surgery


Adverse effects/Contraindications of osmotic diuretics

  • evidence of renal epithelial cell or BBB injury 

  • Heart Failure patients

    • may develop pulmonary edema

  • Electrolyte imbalances

  • dry mouth

  • thirst

  • blurred vision


How does bicarbonate ion regulate Sodium Absorption

  • Na+-H+ exchanger on luminal border allows Na+ to enter the cell in exchange for H+ ion.
  • Next reabsorbed Na+ is pumped out of the cell by Na+-K+-ATPase, whereas, secreted H ion combines with luminal bicarbonate to form carbonic acid.
  • This carbonic acid is dissociated by Carbonic Anhydrase enzyme into water and CO2. CO2 diffuses into the cell and is rehydrated to form carbonic acid. Because the concentration of cellular H+ ion is low, carbonic acid dissociates into H+ and bicarbonate.
  • Thus the constant supply of H+ is furnished for countertransport of Na+ and absorption of bicarbonate.


What is the prototypical carbonic anhydrase inhibitor?



Acetozolamide: MOA

  • As a result:
    • bicarbonate gets retained in the lumen
    • No H+ ion is produced for NHE
    • results in inhibition of Na+ absorption


Carbonic Anhydrase Inhibitors: Therapeutic Uses

  •  edema of congestive heart failure (self limiting diuretic)
    • weak diuretic effect
    • max activity at proximal tubule
      • but Na+ and Bicaronate can be still reabsorbed at distal parts of nephron
  • Other Pharmacological uses:
    • Glaucoma 
      • to reduce intraocular pressure
    • Mountain sickness
      • prophylactic meausre, metabolic acidosis implicated
    • Alkalization of urine
      • enhance excretion of weak acids (uric acid, aspirin)


Carbonic Anhydrase Inhibitors: Adverse effects

  • Metabolic acidosis
    • loss of bicarb buffering
  • Sulfonamide derivative
    • allergic rxn 


What are the Na-K-2Cl Symport Inhibitors

  • Prototype=Furosemide
  • Sulfa-based (-ide)
    • furosemide
    • Bumetanide
    • Torsemide
  • Non-sulfa
    • Ethacrynic acid


What is another name for Na-K-2Cl Symport Inhibitors

  • Loop diuretics
  • High Ceiling diuretics
    • greater effect than other diuretics


illustrate the high ceiling effect of loop diuretics

  • high ceiling-greater effect than other diuretics


What is the MOA of loop diuretics

  • F=Furosemide
    • binds to symporter
  • loss of potassium