9 water ions
TRANSCRIPT
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Body water
Fluid and electrolyte balance
© Department of Biochemistry, 2011 (J.D.)
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Average total body water (TBW) as body weight percentage
465260 y and older
475540 – 59 y
506117 - 39 y
575910 - 16 y
621 - 10 y
651 - 12 months
760 - 1 month
FemalesBothMalesAge
The water content of the body changes:with age - about 75 % in the newborn, usually less than 50 % in the elders,with the total fat (10 % H2O) and muscle (75 % H2O) content,a lean person has high TBW, an obese person has low TBW
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Total body water compartments
interstitial fluid (and lymph)2/31/3
extracellular fluid ECF ICF intracellular fluid
IVFblood plasma
ISF
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Quantification of body fluid compartments (in adult male, 70 kg)
Percentage of
20 %33 %14ECF
5 %8 %3.5IVF (blood plasma)
15 %25 %10.5ISF
40 %67 %28ICF
60 %100 %42 TBW
Body weightBody fluidVolume (Liters)Fluid
The contribution of lymph and transcellular fluid is negligible.
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Transcellular fluidsare secreted by specialized cells into particular body cavities
• cerebrospinal fluid• intraocular fluid• synovial fluid• pericardial, intrapleural, peritoneal fluids• digestive juices • bile• urine
they are usually ignored in fluid balance
Exceptions: heavy vomiting or diarrhea, ascites or exudates may cause fluid imbalances
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Daily water balance (average data, 70 kg male)
2500 mltotal output2500 mltotal input
1500 mlurine
100 mlfeces 300 mlmetabolic water
100 mlsweat1000 mlfood
800 mlinsensible (skin, lungs)1200 mlbeverages
Water outputWater input
Attention should be paid to water intake in children:
– they have higher metabolic rate and large body surface (per body weight)
– they are more sensitive to water depletion
in the elders: the sensation of thirst is often impaired or lacking
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Metabolic water
Examples of metabolic dehydration (1,3) or condensation (2) reactions:
• glycolysis: 2-P-glycerate → H2O + phosphoenolpyruvate
• glutamine synthesis: glutamate + NH3 + ATP → H2O + glutamine + ADP + Pi
• FA synthesis: R-CH(OH)-CH2-CO-S-ACP → H2O + R-CH=CH-CO-S-ACP
100 g of glucose → 55 ml
100 g of protein → 41 ml
100 g of fat → 107 ml
generally:
nutrients + O2 → CO2 + H2O + chemical energy + heat
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Average ion concentrations in blood plasma, ISF, and ICF (mmol/l)
6-2Proteins254Organic anions
100.50.5SO42-
65 *11HPO42- + H2PO4
-
102825HCO3-
8115103Cl-
1511.5Mg2+
traces1.32.5Ca2+
15544K+
10142142Na+
ICFISFBlood plasmaIon
* Most of them are organic phosphates (hexose-P, creatine-P, nucleotides, nucleic acids)
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103
25
18
2
1
5
103
25
2
1
0.5
4
Cl-
HCO3-
Protein-
HPO42-
SO42-
OA
142
4
5
3
142
4
2.5
1.5
Na+
K+
Ca2+
Mg2+
ChargeAnionChargeCation
Molarity (mmol/l)Anion
Molarity (mmol/l)Cation
The average molarity of ions in blood plasma
Total buffer bases: 42 ± 3 mmol/l65 – 85 g/l
total positive charge 154
total negative charge 154
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Comments to ionic composition of body fluids
• blood plasma and ISF have almost identical composition, ISF does not contain proteins
• the main ions of blood plasma are Na+ and Cl-, responsible for osmotic properties of ECF
• the main ions of ICF are K+, organic phosphates, and proteins
• every body fluid is electroneutral ⇒ [total positive charge] = [total negative charge]
• molarity of charge (mmol/l) = mEq/l (miliequivalent per liter)
• in univalent ionic species (e.g. Na+, Cl-, HCO3-) ⇒ molarity of charge = molarity of ion
• in polyvalent ionic species ⇒ molarity of charge = charge × molarity of ion,
e.g. SO42- ⇒ 2 × [SO4
2-] = 2 × 0.5 = 1 mmol/l
• plasma proteins have pI around 5 ⇒ at pH 7.40 they are polyanions
• OA = low-molecular organic anions: lactate, oxalate, citrate, malate, glutamate, ascorbate, KB ...
• hydrogen carbonate, proteins, and hydrogen phosphate are buffer bases
• total plasma proteins are usually expressed in g/l (mass concetration)
• charge molarity of proteins and org. anions is estimated by empirical formulas
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Sodium balance
120-240 mmol/day (urine)[99 % of filtered Na+ is reabsorbed in kidneys]~10 mmol/day (stool), 10-20 mmol/day (sweat)
Output
aldosterone = salt conserving hormoneANP = atrial natriuretic peptide = antagonist of aldosterone
Regulation
130-145 mmol/lgradient between ECF and ICF is created and maintained by Na+, K+-ATPase
Blood level
ECF (50 %), bones (40 %), ICF (10 %)the main cation of ECF, responsible for osmolality and volume of ECF
Distribution
150-280 mmol/daytable salt (NaCl), salty foods (sausages etc.), some mineral waters
Input
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Hormones regulating sodium
excretion of Na+ and water resorption of Na+ excretion of K+
Main effects (in kidneys)
peptidesteroidChemical type
heart atriumadrenal cortexProduced in
Atrial natriuretic peptide AldosteroneFeature
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The loss of sodium under special or pathological situations
The loss by urine• diuretics (furosemid, thiazides)• osmotic diuresis (hyperglycemia in diabetes)• renal failure• low production of aldosterone
The loss by digestion juices• vomiting, diarhea, fistulas etc.
The loss by sweating• work or sports in hot and dry conditions
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Potassium balance
45-90 mmol/day (urine)5-10 mmol/day (stool)
Output
the secretion of K+ into urine (in distal tubule) depends on many factors: K intake, aldosterone production, alkalosis/acidosis, anions in urine
Regulation
3.8-5.2 mmol/l, the gradient between ECF and ICF is maintained by Na+, K+-ATPaseblood level of K+ depends on pH
Blood level
ICF (98 %), ECF (2 %)the main cation of ICF, associated with proteins (polyanions) and phosphates
Distribution
40-120 mmol/daymainly from plant food: potatoes, legumes, fresh and dried fruits, nuts etc.
Input
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pH
K+
pH = 6.8 ~ 7.0 mmol K+ / l
pH = 7.4 ~ 4.4 mmol K+ / l
pH = 7.7 ~ 2.5 mmol K+ / l
Potassium blood level depends on acid-base status
H+ H+
K+K+
cell
H+ H+
K+ K+
cell
cation exchangeacidosis →
hyperkalemia
alkalosis →
hypokalemia
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The hydration of Na+ and K+ cation
• Na+ is the most hydrated ion, typically with 4 or 6 water molecules in the first layer, depending on the environment, Na+ binds water strongly, the hydration shell is stable and moves together with the cation
• any Na+ movement (retention, excretion) is followed by H2O movement• the more salt in ECF, the more water in ECF, the higher volume and blood pressure• potassium ion is larger, has 8 more electrons shielding positively-charged nucleus,
so K+ makes transient associations with water rather than a discrete hydration layer• it also helps to explain why K+ has higher permeability across cell membrane than Na+
Hydrated Free
0,460,27K+
0,520,19Na+
Ion diameter (nm) Ion
K+
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The main species determining the osmolality of blood plasma
proteins
Na+
glucose
urea
water
IVF ICFISF
×
××
×barrier:
blood vessel wallspore-lined
barrier:cell membranehighly selective
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The movement of ions and polar neutral molecules across cell membranesis due to the existence of specific transport proteins (including ion pumps).Diffusion of water molecules is possible, but it is slow and not efficient.
Aquaporins are membrane proteins that form water channels and account for the nearly free and rapid two-way moving of water molecules across most cell membranes (about 3 × 109 molecules per second).
Aquaporin channel structure
Aquaporins consist of six membrane-spanning segmenst arranged in two hemi-pores which fold together to form the "hourglass-shaped" channel.The highly conserved NPA motifs (Asn-Pro-Ala) may form a size-exclusion pore, giving the channel its high specifity.
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In membranes, some of aquaporin types exist as homotetramers, or formregular square arrays.Aquaporins are controlled by means of gene expression, externalization of silenced channels in the cytoplasmic vesicles, and also by the changes in intracellular pH values (e.g., increase in proton production inhibits water transport through AQP-2 and increases the permeability of AQP-6).
More than 12 isoforms of aquaporins were identified in humans, 7 of which are located in the kidney.Examples:AQP1 (aquaporin-1), opened permanently, is localized in red blood cells, endothelial and epithelial cells, in the proximal renal tubules and the thin descendent limb of the loop of Henry.AQP2 is the main water channel in the renal collecting ducts. It increases tubule wall permeability to water under the control of ADH: If ADH binds onto the V2 receptors located in the basolateral membrane, AQP2 in the membranes of cytoplasmic vesicles is phosphorylated and exposed in the apical plasma membrane. Reabsorbed water leaves cells through AQP3 and AQP4 in the basolateral plasma membrane.
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osmolality (mmol/kg H2O) ≈ 2 [Na+] + [glucose] + [urea] (mmol/l)
An osmotic gap can be perceived in this way. The measured value is higher
than the calculated rough estimate, if there is a high concentration
of an unionized compound in the sample (e.g. alcohol, ethylene glycol, acetone). [One gram of ethanol per liter increases the osmolality by about 22 mmol/kg H2O]
Osmolality of blood plasma males 290 ± 10 mmol/kg H2Ofemales 285 ± 10 mmol/kg H2O
Osmolality of blood plasma depends predominantly on the concentrations of Na+, glucose, and urea. Even if the osmolality of a sample is known (it has been measured), it is useful to compare the value with the approximate assessment:
Osmolality of biological fluids is measured by osmometers based mostly on the cryoscopic principle.
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Osmolarity = i c = i × molarity (mmol/l)
Osmolality = i cm = i × molality (mmol/kg H2O)
Distinguish
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Oncotic pressure – colloid osmotic pressure
Oncotic pressure is a small fraction of the osmotic pressure that is induced by plasma proteins.plasma proteins: 62 - 82 g/l (1.3 - 2.0 mmol/l)
plasma albumin: 35 - 50 g/l (0.5 - 0.8 mmol/l)
Albumin makes about 80 % of oncotic pressure.
The capillary wall, which separates plasma from the interstitial fluid, is freely permeable to water and electrolytes, but restricts the flow of proteins.
Osmotic pressure of blood plasma: 780 - 795 kPaOncotic pressure of blood plasma: 2.7 - 3.3 kPa
2.7 – 1.4 kPa ... sizable edemas, imminent danger of pulmonary edema < 1.4 kPa ... unless albumin is given i.v., survival is hardly possible
Within the extracellular fluid, the distribution of water between bloodplasma and interstitial fluid depends on the plasma protein concentration.
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The capillary wall is permeable for small molecules and water but not permeable for proteins.
The hydrostatic pressure of a blood tends to push water out of the capillary – filtration.
The oncotic pressure pulls the water from the interstitial space back into the capillary - resorption.
The significance of oncotic pressure
Blood capillary
Endothelial cells
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The movement of fluid between plasma and interstitial fluid
Oncotic pressure can be measured by means of colloid osmometers.
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Six cases of water/sodium imbalance
„pure“ sodium„pure“ sodium
„pure“ water„pure“ water
isotonic fluidisotonic fluid
The overload byThe loss of
For more details see physiology
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ICF
ECF
The loss of isotonic fluid
Normalstatus
The loss of isotonic fluid = isotonic dehydration
↓ ECF volume (hypovolemia)
activation of RAAS
Consequence
vomiting, diarrhea, bleeding, burns,(ascites)
Typical situation
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ICF
ECF
The loss of pure waterNormalstatus
H2O
The loss of pure (solute-free) water/hypotonic fluid = hypertonic dehydration
hypovolemiaECF becomes hypertonic (hypernatremia)water osmotically moves from ICF to ECFcellular dehydration (cells shrink)*ADH production ↑ (water retention)
Consequences
hyperventilationno drinking (older people) osmotic diuresisADH deficit (diabetes insipidus)
Typical situations
* The shrinking of brain neurons disturbs brain functions (confusion, delirium, convulsions, coma)
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ICF
. .. . . .
ECF
The loss of salt Normalstatus
H2O
The loss of pure sodium (salt)
ECF becomes hypotonic (hyponatremia)water osmotically moves from ECF to ICF →hypovolemia + intracellular edemas
expansion of ICF → increase of intracranial pressure - imminent danger of cerebral edemas
ADH production ↓ (water excretion) + RAAS activation
Consequences
aldosterone deficitdiuretics(also vomiting, sweating, diarrhea)
Typical situations
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ICF
ECF
The overload by isotonic fluid
Normalstatus
The overload by isotonic fluid = isotonic hyperhydration
expansion of ECF volumeECF edema
Consequences
excessive infusions by isotonic salinecardial insufficiencyrenal diseases (secondary hyperaldosteronism)
Typical situations
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ICF
. . . . . . . . .
ECF
The overload by water Normalstatus
The overload by pure (solute-free) water/hypotonic fluid = hypotonic hyperhydration (water intoxication)
ECF volume expansionECF becomes hypotonic (hyponatremia) water moves osmotically to ICFICF + ECF edemasADH production ↓ (water diuresis)
Consequences
excessive drinking simple waterSIADH*, also stress, trauma, infectionsgastric lavageexcessive infusion of glucose solution
Typical situations
H2O
* syndrome of inappropriate ADH
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ICF
ECF
The overload by sodiumNormalstatus
The overload by pure sodium/salt
ECF becomes hypertonic (hypernatremia) → hypervolemiawater moves osmotically from ICF to ECFECF (pulmonary) edemas + cellular dehydration↑ ADH (to retain water)↑ ANP / urodilatin (to excrete sodium)RAAS inhibited
Consequences
excessive intake of salt / mineral watersdrinking sea water (ship wreck)excessive infusions of Na-salts (ATB ...)aldosterone hyperproduction
Typical situations
H2O
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Water and osmolality control
Antidiuretic hormone (ADH, Arg-vasopressin, AVP) released from the nerve terminals in posterior pituitary
Aldosterone secreted from the zona glomerulosa of adrenal cortex after activation of the renin-angiotensin system
Natriuretic peptides (ANP, BNP) secreted from some kinds of cardiomyocytes in heart atria and chambers
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OSMOSENSORShypothalamus liver
VOLUMOSENSORS heart juxtaglomerular cells
WATER INTAKE
Sensation of thirst
RenalRETENTION OF WATER RETENTION OF Na+
INTAKE OF Na+ WATER LOSS
Osmolality increase Decrease in ECF volume
Water and osmolality control is closely inter-related
Filling of heart upper chambers Filling of arteries
Secretion of ADH (vasopressin)
Increaseof HMV
Secretion of renin
Better fillingof arteries
Secretion ofaldosterone
Antagonistic action ofnatriuretic peptides ANP and BNP
For details see physiology
Example
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Antidiuretic hormone (ADH, Arg-vasopressin, AVP)
is a nine amino acid cyclic peptide:
Cys–Tyr–Phe–Gln–Asn–Cys–Phe–Arg–Gly
S S
Vasopressin receptors V2 are in the basolateral membranes of renal collecting ducts.
Vasopressin receptors V1 are responsible for the vasoconstriction.
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The renin-angiotensin aldosterone system (RAAS)
THE JUXTAGLOMERULAR CELLSof the renal afferent arterioles
Fluid volume decreaseBlood pressure decreaseBlood osmolality decrease
Stimulation of ALDOSTERONE production in zona glomerulosa cells of adrenal cortex
Vasoconstriction of arterioles
angiotensin-converting enzyme(ACE, a glycoprotein in the lung,endothelial cells, blood plasma)
release into the blood
ANGIOTENSINOGEN(blood plasma α2-globulin, >400 AA)
ANGIOTENSIN II
ANGIOTENSIN I
ANGIOTENSIN III
Rapid inactivationby angiotensinases
Protein
His-Leu
(a decapeptide)
(an octapeptide)
renin(a proteinase)
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Angiotensin II and III
NH2–Asp–Arg–Val–Tyr–Ile–His-Pro–Phe–His–Leu–Leu–Val–TyrN-Terminal sequence of the plasma α2-globulin angiotensinogen:
reninDecapeptide angiotensin I:
NH2–Asp–Arg–Val–Tyr–Ile–His-Pro–Phe–His–Leuangiotensin converting enzyme (ACE)
Octapeptide angiotensin II: NH2–Asp–Arg–Val–Tyr–Ile–His-Pro–Phe
aminopeptidase
Heptapeptide angiotensin III: Arg–Val–Tyr–Ile–His-Pro–Phe
inactivating angiotensinases
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Aldosterone acts on gene expression level Induces the synthesis of Na / K channels, and Na/K-ATPase
Natriuretic peptides
K+K+
Na+Na+
3 Na+
2 K+
H2Oaquaporin 3
ATP
H2O0aquaporin 2
Tubular lumen
receptors V2
Aldosterone
for ADH
Blood plasma
urine
blood
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Natriuretic peptides (more types are known)
brain natriuretic peptide (BNP)(mainly of cardiac ventricular origin)
atrial natriuretic peptide (ANP)
Both peptides have a cyclic sequence (17 amino acyl residues) closedby a disulfide bond; ANP consists of 28 residues, BNP of 32.
They originate from C-ends of their precursors by hydrolytic splitting and have short biological half-lives. Released N-terminal sequences are inactive, but because they are long-lived, their determination is useful.
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Membrane receptors for natriuretic peptides are of unique kind –
they exhibit intrinsic guanylate cyclase activity;
binding of natriuretic peptides onto receptors increases intracellular
concentration of cGMP.
Both ANP and BNP have been shown
- to have diuretic and natriuretic effects,
- to induce peripheral vasodilatation, and
- to inhibit release of renin from kidneys and aldosterone from adrenal cortex
These peptides are viewed as protectors against volume overload and
as inhibitors of vasoconstriction (e.g. during a high dietary sodium intake).
Natriuretic peptides are antagonists of aldosterone