Osmoregulation Part 3

1
Osmoregulation Part 3

• Regulation of pH
• Urine-concentrating Mechanism
• Control of Water Reabsorption
• Miscellaneous Topics including Nitrogenous Waste
  Excretion

2
Regulation of pH

• CO2 - HCO3 buffering system determines the pH
  of the extracellular space 2 factors control pH
  in mammals
• Excretion of CO2 via the lungs
• Excretion of acid (H ions) via the kidneys
  maintains plasma bicarbonate concentration in
  mammals
• HCO3 (high) and H (low) concentration in
  Glom ultrafiltrate to plasma, yet urine pH 6
  with little HCO3 acid (H) must be added to
  filtrate most HCO3 must be removed

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Regulation of pH cont

• Protons (H) added to the filtrate along the
  entire tubule, the filtrate becomes progressively
  more acidic
• Proximal tubule LofH protons secreted via
  Na/H antiporter
• Distal tubule and collecting ducts have
  specialized cells (A-type cells) possessing
  proton pump (apical membrane) Cl-/HCO3 exchange
  system (basolateral membrane)

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Type-A Cells cont

• Contain high levels of carbonic anhydrase
  (catalyzes hydration of intracellular CO2 HCO3
  and H formed rapidly i.e. CO2 H2O H HCO3)
  H cross apical side to tubule lumen HCO3
  cross basolateral side to interstitial fluid
  uptake of HCO3 into blood acid secreting cells
• Removal of H creates negative gradient
  enhances Na reabsorption (apical membrane) from
  filtrate intracellular Na kept low by Na/K
  pump (basolateral membrane) transporting Na to
  the extracellular fluid (K channels on apical
  side)
• Acidification of urine associated with Na
  reabsorption

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Type-B Cells

• Also specialized cells in distal tubule
  collecting duct also have Cl-/HCO3 exchanger in
  apical membrane
• Type-B cells contain Carbonic anhydrase secret
  HCO3 into the tubule lumen exchanging for Cl-
• Protons (H) Cl- move across basolateral
  membrane via a proton pump Cl- channels

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Regulating pH by altering activity of Type-A -B
cells

• Activity of A-cells (acid secretion) increases
  during acidosis and activity of B-cells
  (bicarbonate secretion) increases during
  alkalosis
• H secretion by tubule reduces pH of
  ultrafiltrate increases the gradient against
  which protons are transported when the pH of
  ultrafiltrate drops below 4.5, acid secretion
  stops unless ultrafiltrate is buffered (by HCO3,
  phosphates and ammonia they compete for H)
• Tubule membrane impermeable to phosphates and
  ammonium ions excreted in the urine

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Buffering cont

• Phosphates in ultrafiltrate filtered from blood
  in glom. whereas ammonia diffuses from blood
  across the tubular cells into the lumen
  (converted to ammonium ions)
• (phosphate level depends on diet with excess
  found in urine i.e. independent of acidbase
  requirements (note FUS - struvite crystals are
  mainly phosphorous and magnesium, which form in
  an alkaline urine pH)

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Buffering cont

• Acidosis plasma HCO3 falls HCO3 in filtrate
  decreases meaning less is available for buffering
  then ammonia plays greater role in elimination
  of excess acid
• NH3 produced in renal tubule cells by enzymatic
  deamination of aas (esp. Glutamine) (also NH3
  continuously mnft by liver but toxic so must be
  converted to urea and glutamine) to produce NH4
  (which traps both N atoms H in the urine
  serves as a vehicle for their excretion

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Urine Concentrating Mechanism

• Urine concentrated by osmotic removal of water in
  the collecting ducts (hypertonic relative to body
  fluids) also related to length of LofH I.e. the
  longer, the more hypertonic urine e.g. kangaroo
  rat
• In addition, concentrating ability of nephron
  also due to osmolarity of interstitial fluid in
  kidney progressively increasing toward deeper
  regions of renal medulla (suggested a
  counter-current multiplier system in effect p.
  611)

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Countercurrent Multiplier System

• Defn (from text) a pair of opposed channels
  containing fluids flowing in opposite directions
  having an energetic gradient directed
  transversely from one of the channels into the
  other since exchange due to the gradient is
  cumulative with distance, the exchange per unit
  distance will be multiplied as a function of
  the total distance over which exchange takes place

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Urine Concentrating Mechanism cont

• Functional asymmetry between the descending
  ascending limbs of LofH countercurrent
  multiplier principle interstitial
  corticomedullary osmotic gradient - established
  by combination of active transport of NaCl from
  ascending segment selective passive perm to
  water, salt and urea along specific segments of
  nephron (desc high water, low urea and low salt
  perm ascend low water, low urea and high salt
  perm)
• Net loss of water salt in LofH and distal
  tubule, filtrate entering collecting duct high
  urea concentration

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Urine Concentrating Mechanism cont

• As collecting duct passes into the depths of
  medulla highly perm to urea leaks down its
  conc gradient thus raising interstitial
  osmolarity of inner medulla (this draws water
  from desc limb LofH producing very high
  intratubular solute concentration at the bottom
  of the loop
• As highly conc tubular fluid flows up highly
  salt-perm thin seg of ascend NaCl leaks out
  down its concentration gradient see Fig. 14-34 p.
  612 Fig 14-28 p. 605 for summary of gradients
  activities
• Note countercurrent mechanism in vasa recta
  maintains the standing conc gradient in the
  interstitium p. 613

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Control of Water Reabsorption

• Rate of water drawn across wall of collecting
  duct depnds on water perm of the wall which is
  regulated by ADH (antidiuretic hormone) which
  ultimately controls amount of water in urine
• ADH action increase aquaporins in apical mem.
  of collecting duct (by moving water channel
  proteins from vesicular stores to the apical
  membrane)
• Note ADH also causes urea transporter protein
  (UT2) to move from vesicular stores to apical
  membrane inc. urea flux from urine to renal
  medu. coupled to Na in antiport fashion ADH
  stim. both water and urea reabsorption

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More on ADH

• ADH secreted by hypothalamus these cells are
  sensative to inc. plasma osmolarity I.e. as
  plasma osm. Increases (e.g. dehydration), more
  ADH secreted thus more water reabsorbed as ADH
  stim more perm to water etc. urine more conc
• Inhibitory input from arterial atrial
  baroreceptors respond to changes in blood
  pressure e.g. hemorrhage BP dec. red.
  Activity of inhibitory cells inc/ sec. ADH
  water reabsorb help maintain blood volume
• Excellent brief review on p. 614 - feedback
  mechanism under endrocine or nervous or both
  control

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Excretion of Nitrogenous Wastes

• Catabolism of aas release the amino group NH2
  (deamination) or transferred to another molecule
  for removal/reuse (removal dissolved in water
  excreted avoid toxic levels of nitrogenous
  wastes esp. ammonia convulsions, coma and/or
  death most excreted as ammonia, urea or uric
  acid rest as creatinine, creatine, or other
  aas etc.)
• Water is needed as ammonia excretion occurs by
  diffusion different amounts needed i.e. ammonia
  the most, next urea and the least for uric acid
  availability of H2O determines the nature/pattern
  of nitrogen excretion species differences exist

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Excretion of Nitrogenous Wastes Species
Differences

• Aquatic animals (ammonotelic) ammonia via gills
• Terrestrial animals (ureotelic) urea or uric
  acid uricotelic) via kidneys
• Terrestrial birds 90 as uric acid/3-4 as
  ammonia semi-aquatic birds 50 as uric
  acid/30 as ammonia
• Mammals mostly urea excretion