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Pharmocology- Unit Two
Renal Review (T Pierce)
33
Medical
Professional
09/11/2009

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Term
transporters in PCT
Definition
  • on lumen side
    • Na/H antiporter (Na reabsorbed, H into tubule)
    • Cl/organic base antiporter (Cl reabsorbed)
  • on interstitial/blood side
    • Na/K pump
    • HCO3 channel
      • for each HCO3 reabsorbed, there is one hydrogen secreted into lumen
    • symporters (reabsorbed
      • Na/glucose
      • Na/phosphate
      • Na/AA
Term
Drugs: organic anions secreted by PCT
Definition
  • acetazolamide (CA inh.)
  • chlorothiazide (thiazide diuretic)
  • furosemide (loop diuretic)
  • penecilin
  • probenecid
  • salicylate (aspirin)
  • HTZ (thiazide diuretic)
  • bumetanide
Term
Drugs: organic cations secreted by PCT
Definition
  • atropine (muscarinic antagonist)
  • isoproterenol
  • cimetidine
  • morphine
  • quinine
  • amiloride
  • procainamide
Term
Mechanism of isoosmotic reabsorption in the PCT
Definition
  • sodium is reabsorbed with bicarbonate in the early PCT
  • in the lat PCT, chlorine is very concentrate
  • Cl and Na are reabsorbed at this point via paracellular pathway
  • water will follow NaCl due to osmosis
Term
Clinical importance of organic acid and base transporters in PCT
Definition
  • drugs that our bound to protein cannot enter nephron lumen UNLESS these transporters secrete them into the lumen
  • they have a finite rate of secretion
    • so two drugs may have to compete for the same transporters
    • this alters rate of elimination/action
Term
channels in TAL and properties
Definition
  • lumen side
    • NKCC channel (all reabsorbed)
    • K channel (secreted)
      • causes positive potential drives movement of Mg and Ca into blood
  • interstitium/blood side
    • Na/K pump
    • K/Cl cotransport

Called diluting segment due to its impermeability to water

Term
Branching of blood supply to kidney
Definition
  1. renal artery branch into interlobar A.'s
  2. interlobar into arcuate A's
  3. arcuate A's into interlobular A's
  4. interlobular into afferent arteriole
  5. afferent arteriole into glomerular capillaries
  6. glomerullar capillaries into efferent arteriole
  7. two options
    1. outer cortex: efferent arteriole into peritubular capillaries
    2. inner cortex: efferent arteriole into vasa recta
Term
What part of the kidney would you find the greatest blood flow?
Definition
  • cortex (decreases as we go inward to medulla)
Term
Location of JGA in relation to nephron
Definition
  • in conjunction with the early DCT
Term
Compare the amount of filtrate produced with the amount of urine produced. What can we say about what is happening then?
Definition
  • 180 L if filtrate produced a day, but only 1.5 L of urine/day
  • this means most of the filtrate is reabsorbed
    • ex: AA, urea, ions, glucose
Term
What channel drives the transport process through the kidney?
Definition
  • 3Na/2K ATP pump at the basolateral membrane of tubule cells (establishes ionic gradient)
Term
Mechanism of water reabosrption
Definition
  • can be transcellular or paracellular
  • follows solute absorption
  • water absorption can also resulte in "solvent drag"
Term
Clinical importance of secretion of drugs into PCT
Definition
  • many drugs are bound to a protein, so they cannot enter the lumen via filtration
  • only way protein bound is via secretion
Term
Fate of chloride in the late PCT
Definition
  • at this point, Cl becomes concentrated
  • reabsorbed along with sodium via paracellular pathway with water following
Term
Nature of permeability of tDL
Definition
  • water permeable but impermeable to NaCl
    • water is reabsorbed
    • NaCl concentrated in the tubule
Term
channels of DCT
Definition
  • Na/Cl cotransporter (into cell) on luminal side
  • Ca channel (into cell) on luminal side
  • Na/K pump on basolateral side
  • Na/Ca antiport (Na in, Ca out) on basolateral side (driving force for calcium reabsorption)
Term
CD cell types
Definition
  • principle cells
  • intercalated cells
Term
channels of principle cells of CD
Definition
  • sodium channel (sodium into cell) on lumen side
  • potassium channel (potassium into lumen) on lumen side
  • V2 channel (water into cell) on lumen side
  • Na/K pump on basolateral side
Term
channels of intercalated cells of CD
Definition
  • H/ATPase pump (H into lumen) on luminal side
  • K/H pump (H into lumen, K into cell) on luminal side
  • K channel (K out) on basolateral side
  • HCO3/Cl antiport (HCO3 into blood, Cl into cell) on basolateral side
Term
Effect of adding 2 L of isotonic saline
Definition
  • increase in ECF volume
  • no increase in osmolality of any compartment
  • no change in volume of ICF
Term
Effect of adding 2 L of water to ECF
Definition
  • decreased osmolarity in both ECF, ICF
  • increased volume in both ECF and ICF
Term
effect of adding 290 mmol of NaCl to ECF
Definition
  • ECF volume increase
  • ICF volume decrease
  • increase osmolality in both compartments
Term
What channel is responsible for creating the corticomedullary osmotic gradient via counter current multiplier? What compound will reabsorb from CD in the presence of ADH with this system?
Definition
  • Na/2Cl/K channel in TAL
  • urea reabsorbed from collecting duct along with water
Term
How does the countercurrent exchanger work?
Definition
  • via the vasa recta
  • as we go more inside the medulla of the kidney nephron, we see recirculation of solutes
    • at descending arm, water out and solutes in
    • at ascending arm, solutes out, water in
  • this leads to recirculation
Term
Mechanism of secretion of ADH
Definition
  1. body senses increase in plasma osmolality (senses at about 280 mOsm/kg H2O)
    • could also fire to significant decreases in volume
  2. stimulation of osmoreceptors in the supraoptic and paraventricular areas of hypothalamus
  3. ADH produced by hypothalamus and released from post. pit.
  4. ADH bind to principle cell R's in CD
  5. upgregulates adenylate cyclase, leading to increase cAMP
  6. activate PKA, leading to phosphorylation of vesicles containing V2 channels
  7. V2 channel vesicles fuse with apical cell membrane
  8. increase water and urea reabsorption
    • decrease urine volume
    • increase urine osmolality
Term
Mechanism of macula densa knowing when to stimulate the release of renin
Definition
  1. NaCl transported into macula densa cells via Na/K/Cl
  2. when it is high
    • inhibit COX2 enzyme from making PG
  3. when it is low
    • COX2 produce PG's
    • via Gs mechanism, stimulate granular cells to release renin

Also, when ATP hydrolyzed, can produce ADO and inhibit cAMP, thereby inhibit renin release.

Term
Aside from the stimulation of the macula densa, what are the other ways the JGA knows to release renin?
Definition
  • decreased effective circulating volume could be sensed by baroR leading to increased sympathetic stimulation of granular cells via beta 1
  • decrease renal perfusion pressure in afferent arterioles
Term
Effect of increased levels of ang II
Definition
  • intrarenal and systemic vasoconstriction
  • increased PCT sodium reabsorption
  • increased Ald, leading to increased sodium reabsorption, increased potassium and hydrogen excretion
  • increased ADH, leading to increased water reabsorption
Term
Ang 1-7 (mechanism of production, effect on body, effect of ACE inhibitor on it)
Definition
  • mechanism of production (serves as counter regulatory pathway for production of Ang II)
    • produced from Ang II via ACE2
  • effect on body
    • produces vasodil.
    • inhibits prolif. of vascular smooth muscle
  • clinical app.- ACE inhibitors usually dont inhibit ACE2, but rather increase circulating levels of Ang 1-7
Term
What causes the release of Ald?
Definition
  • increase plasma potasssium
  • increase levels of Ang II
Term
Mechanism of action of Aldosterone
Definition
  • principle cells
    • increase active Na channels on lumen side
    • increase Na/K pump activity
    • increase K channel activity
    • increase Na/H antiport activity
  • intercalated cells
    • increase H/ATPase activity

Happens over a period of hours to days. Remember, its a steroid hormone that translocates to the nucleas via activated receptor complex

Term
Potential causes of metabolic alkalosis
Definition
  • loop and thiazide diuretics
  • vomiting
  • hyperAld
Term
potential causes of metabolic acidosis
Definition
  • diarrhea
  • DM
  • CA inh.
  • K sparring diuretics
  • renal failure
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