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Control of ECF osmolality and volume. MAIN DIFFERENCES BETWEEN ICF AND ECF. More Na + in ECF More K + in ICF More Cl - in ECF More PO 4 , HCO 3 , and Pr - in ICF. These differences are maintained by transport processes in the cell membrane. - PowerPoint PPT Presentation
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Control of ECF Control of ECF osmolality and osmolality and
volumevolume
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
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
Distribution of Na+ and K+ in the body
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
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)
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
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
Sensors:
1. Extrarenal baroreceptors
Carotid sinuses
Arteries
Great veins
Atria
2. Renal juxtaglomerular apparatus
Efferents:
1. Renal sympathetic nerves
2. Macula densa renin angiotensin II aldosterone
Control of GFR:
1. Angiotensin II efferent arteriolar constriction PGC
2. Renal sympathetic nerves Na+ adrenergic receptors Constriction of afferent and efferent arterioles PGC
Osmoreceptor -Osmoreceptor -ADH mechanismsADH mechanisms
Renal handling of NaCl and water:
NaCl & H2O are freely filterable at the glomerulus.
There is extensive tubular reabsorption but notubular secretion.
Na+ reabsorption is driven by the basolateral Na+/K+-ATPase and is responsible for the major energy expenditure in kidney.
a. Na+ entry per se by SFD
Na+
GlNa+
HNa+
Cl
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
Mechanisms of Sodium Reabsorption:
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%.
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+.
Solute
Na+
Solute transport in PCT
3 Na+
2 K+
S
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
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.
a. thin ALH reabsorption of of NaCl
b. thick ALH co-transport of Cl- & Na+ (carrier transports Na+, K+, 2Cl-)
3 Na+
2 K+Na+
2Cl-
K+
Transport processes in the thick ascending limb
K+
H+
Na+ H2O+CO2H2CO3
H+ + HCO3 HCO3-
+C
A
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.
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.
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+.
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.
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.
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.
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.
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.
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.
Aquaporin-2
H2O
3 Na+
2 K+
ADH
Adenyl cyclasecAMP
Effect of ADH on collecting tubule cells
Summary:
osmolality
Stimulation of osmoreceptors in anterior hypothalamusSupraoptic &
paraventricular Nuclei
Posterior pituitary ADH
permeability of LDT, CCD, MCD to H2O
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
Thirst mechanism
Thirst (conscious desire for water):
Under hypothalamic osmoreceptor control
Water intake is regulated by- increased plasma osmolality- decreased ECF volume- psychological factors
Stimulus:
Intracellular dehydration due to increased osmolar concentration of ECF
Excessive K+ loss Low intracellular K+ in osmoreceptors
Mechanism is activated by
The arterial baroreceptor reflex BP
The volume receptors- low pressure receptors in atria; CVP
Angiotensin II
Increased Na+ in CSF
Hyp
Hypertonicity
Osmoreceptors
Hypovolaemia
BaroreceptorsAngiotensin II
Thirst
Thirst center:
Subfornical organ
Organum vasculosum of the lamina terminalis
Other factors regulating water intake:
Psycho-social
Dryness of pharyngeal mucous membrane
? Gastrointestinal pharyngeal metering
Renin-angiotensin Renin-angiotensin –aldosterone –aldosterone
systemsystem
Renin:
Produced by
Juxtaglomerular cells – located in media of afferent arterioles
Lacis cells – junction between afferent and efferent arterioles
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
Renin
Angiotensinogen Angiotensin I
Angiotensin-converting enzyme
Angiotensin I Angiotensin II
Adrenal cortex Aldosterone
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)
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+
Salt appetiteSalt appetite
ECF Na+
Blood volume
Hypothalamic centers
Salt appetite
Potassium Potassium excretionexcretion
Renal handling of K+:
800 mEq/day enter the filtrate
100 mEq/day is secreted
PCT – reabsorption
DCT and CD – both reabsorption and secretion
Secretion is mainly by the Principal cells
3 Na+
2 K+
Na+
K+
Aldosterone
ENaC Nucleus
ENaC = epithelial sodium channels
Control by P cells
1. Na:K pump
2. Electrical gradient from blood to lumen
3. Permeability of luminal cell membrane to K+
Stimulation Inhibition
ECF K+ Acidosis
Aldosterone
Urine flow rate
The End