Control of ECF osmolality and volume

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Control of ECF osmolality and volume
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MAIN DIFFERENCES BETWEEN ICF AND ECF

• More Na in ECF
• More K in ICF
• More Cl- in ECF
• More PO4, HCO3, and Pr- in ICF

These differences are maintained by transport
processes in the cell membrane
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Distribution of Na and K in the body
Na K
Total intracellular 9.0 89.6
Total extracellular 91.0 10.4
Plasma 11.2 0.4
Interstitial fluid 29.0 1.0
Connective tissue 11.7 0.4
Bone 36.5 7.6
Transcellular 2.6 1.0
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• ECF volume
• 20 of body weight
• 14 L (in a 70 kg man)
• 3.5 L plasma 10.5 L interstitial fluid
• Measured by using inulin, mannitol or sucrose

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• Osmolar concentration of plasma
• 290 mosm/L - 142 mEq/L Na
• Tonicity Osmolality of a solution in relation
  to plasma - isotonic, hypertonic, hypotonic
• 0.9 saline is isotonic
• 270 mosm/L is contributed by Na, Cl- and HCO3-
• Plasma proteins contribute less than 2 mosm/L (28
  mm Hg oncotic pressure)

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Ranges of salt and water intake and
excretion a. Salt intake from 50 mg to 25
g/day b. Water excretion from 400 ml to 25 l/day
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• Total body sodium is relatively constant.
• Freely filtered
• Reabsorbed but not secreted
• Therefore,
• Na excretion Na filtered Na reabsorbed
• (GFR X Pna) - Na reabsorbed
• Pna is relatively constant
• Therefore control is exerted by
• GFR
• Na reabsorption

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• Sensors
• Extrarenal baroreceptors
• Carotid sinuses
• Arteries
• Great veins
• Atria
• 2. Renal juxtaglomerular apparatus
• Efferents
• Renal sympathetic nerves
• Macula densa ?renin ?angiotensin II ? aldosterone

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• Control of GFR
• Angiotensin II ?efferent arteriolar constriction
  ?? PGC
• Renal sympathetic nerves ?Na ?? adrenergic
  receptors ?Constriction of afferent and efferent
  arterioles ?? PGC

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Osmoreceptor -ADH mechanisms
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Renal handling of NaCl and water NaCl H2O are
freely filterable at the glomerulus. There is
extensive tubular reabsorption but no tubular
secretion. Na reabsorption is driven by the
basolateral Na/K-ATPase and is responsible for
the major energy expenditure in kidney.
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Mechanisms of Sodium Reabsorption
a. Na entry per se by SFD
b. Na co-transported with glucose or organic
acids
c. Na counter-transported with intracellular H
d. Na co-transported with Cl-
e. Na following Cl- diffusion through tight
junctions
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• Proximal Tubule
• The PT is highly permeable to water.
• Reabsorbs 65 of filtered sodium (active
  transport) and water plus organic nutrients etc.
• Water reabsorption is passive, along osmotic
  gradients and keeps pace with solute.
• Therefore, the Na remains virtually constant
  through the PT, whereas the mass of Na is
  reduced by 65.

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• Movement of water is facilitated by the presence
  of water channels - aquaporin 1, in the apical
  membranes of proximal tubule epithelial cells
• Late in the PT, some Na is also reabsorbed by
  simple diffusion and solvent drag.
• Cl- initially lags behind and the concentration
  gradient is established by water reabsorption.
• Accordingly, in the middle and late PT, Cl- is
  the major anion coupled with Na.

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At the end of the PT 1. Luminal osmolality is
isotonic 2. The concentration of Cl- is
higher 3. The concentration of HCO3- is lower
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• Loop of Henle
• Reabsorbs a further 25 of the filtered NaCl plus
  15 of filtered water.
• The descending limb does not reabsorb NaCl.
• The entire ascending limb of loop of Henle does.
• thin ALH ? reabsorption of of NaCl
• b. thick ALH ? co-transport of Cl- Na (carrier
  transports Na, K, 2Cl-)

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The ALH, unlike the PT, reabsorbs more solute
than water, therefore delivers hypotonic urine to
the distal tubule. The decrease Na is greater
than the decrease in osmolality due to the
addition of urea to lumen in the ALH. Drugs
that inhibit transport of Cl- in the ALH
therefore also inhibit Na reabsorption producing
diuresis.
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Distal Tubule Collecting Duct NaCl
reabsorption continues along the DT CT so that
the final urine contains 1 of the filtered
mass. H2O permeability of the early DT is
extremely low and not subject to physiological
control. Accordingly almost no water is
reabsorbed in the early distal segment.
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H2O permeability of the late DT Water
permeability of distal tubule and initial
collecting tubule, is also extremely
low. However under the influence of ADH it
becomes highly water permeable. Further removal
of solute in the EDT presents the LDT with
markedly hypotonic urine containing even less Na
Removal of Na continues in the LDT and
collecting system, so that the final urine may
contain virtually no Na.
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Anti-diuretic hormone ADH (antidiuretic
hormone), vasopressin or arginine vasopressin
(AVP) is the major regulator of urine osmolality
and urine volume. ADH is a nonapeptide produced
by neurons in the supraoptic and paraventricular
nuclei of the hypothalamus. The axon terminals
of these neurons reside in the posterior
pituitary. ADH is stored in these axon
terminals.
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When ADH is released from the posterior pituitary
it causes the kidney to produce urine that is
high in osmolality and low in volume. In the
absence of ADH the kidney tends to produce a
large volume of urine with low osmolality.
Total solute excretion is relatively constant
over a wide range of urine flow rates and
osmolalities.
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Control of ADH release 1. Increased osmolality
of ECF is a powerful stimulus for ADH release a
1 change in osmolality induces significant
increase in ADH release. Hypothalamic
supra-optic and paraventricular nuclei respond to
increased osmolality of ECF by producing ADH. As
a result of this high sensitivity, responses to
increased osmolality occur rapidly.
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Control of ADH release 2. Volume In a
volume-depleted individual, the release of ADH is
more sensitive to increased osmolality. In a
volume-expanded state, ADH release is less
sensitive to increases in osmolality. 3.
Decreased blood pressure or blood volume also
enhance ADH release, but not with such high
sensitivity 5 to 10 changes are required to
alter ADH secretion.
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Effects of ADH on the kidney ADH increases the
water permeability of the epithelial cells of
late distal tubules and the collecting tubules
May also increase NaCl absorption in the thick
ascending limb of the loop of Henle. ADH also
increases the urea permeability of the inner
medullary collecting tubules.
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Action of ADH Binds to receptors in the
basolateral membrane, causing increased cAMP.
This results in rapid insertion of aquaporin-2
protein channels into the luminal membrane of
principal cells. The water channel proteins are
present in preformed intracellular vesicles, so
this up regulation of water permeability can
occur quickly. The water channels can be
rapidly re-internalized when ADH is no longer
present.
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Effect of ADH on collecting tubule cells
Aquaporin-2
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Summary
Stimulation of osmoreceptors in anterior
hypothalamus
? osmolality
Supraoptic paraventricular Nuclei
Posterior pituitary ADH
? permeability of LDT, CCD, MCD to H2O
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Summary of handling of Na by the kidney
Glomerular filtrate 26 000 mEq/Day
PCT 65 Active transport
Thick ascending loop 27 Active transport
LDCT 8 Aldosterone
Cortical collecting duct Aldosterone
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Thirst mechanism
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• Thirst (conscious desire for water)
• Under hypothalamic osmoreceptor control
• Water intake is regulated by - increased plasma
  osmolality - decreased ECF volume -
  psychological factors

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Stimulus Intracellular dehydration due to
increased osmolar concentration of ECF Excessive
K loss ? Low intracellular K in osmoreceptors
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• Mechanism is activated by
• The arterial baroreceptor reflex ? BP
• The volume receptors- low pressure receptors in
  atria ? CVP
• Angiotensin II
• Increased Na in CSF

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Hypertonicity
Hypovolaemia
Baroreceptors Angiotensin II
Osmoreceptors
Hyp
Thirst
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Thirst center Subfornical organ Organum
vasculosum of the lamina terminalis
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• Other factors regulating water intake
• Psycho-social
• Dryness of pharyngeal mucous membrane
• ? Gastrointestinal pharyngeal metering

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Renin-angiotensin aldosterone system
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Renin Produced by Juxtaglomerular cells
located in media of afferent arterioles Lacis
cells junction between afferent and efferent
arterioles
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• Factors affecting renin secretion
• Stimulatory
• Increased sympathetic activity via renal nerves
• Increased circulating catecholamines
• Prostaglandins
• Inhibitory
• Increased Na and Cl- reabsorption in macula
  densa
• Angiotensin II
• Vasopressin

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Renin ? Angiotensinogen ?Angiotensin
I ? Angiotensin-converting enzyme Angiotensin I
?Angiotensin II ? Adrenal cortex ?Aldosterone
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• Actions of angiotensin II
• Arteriolar vasoconstriction and rise in SBP and
  DBP
• On adrenal cortex to produce aldosterone
• Facilitates release of noradrenaline
• Contraction of mesangeal cells - ?GFR
• Brain - ? sensitivity of baroreflex
• Brain - increases water intake (AP, SSFO, OVLT)

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Actions of aldosterone Increased reabsorption of
Na from urine, sweat, saliva and GIT ECF
volume expansion Kidney P cells increased
amounts of Na are exchanged for K and H
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Salt appetite
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• ECF Na
• Blood volume

Hypothalamic centers
? Salt appetite
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Potassium excretion
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• Renal handling of K
• 800 mEq/day enter the filtrate
• 100 mEq/day is secreted
• PCT reabsorption
• DCT and CD both reabsorption and secretion

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Secretion is mainly by the Principal cells
ENaC epithelial sodium channels
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• Control by P cells
• NaK pump
• Electrical gradient from blood to lumen
• Permeability of luminal cell membrane to K
• Stimulation Inhibition
• ? ECF K Acidosis
• Aldosterone
• Urine flow rate

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The End