9 water ions


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9 water ions

  1. 1. Body waterFluid and electrolyte balance © Department of Biochemistry, 2011 (J.D.) 1
  2. 2. Average total body water (TBW) as body weight percentage Age Males Both Females 0 - 1 month 76 1 - 12 months 65 1 - 10 y 62 10 - 16 y 59 57 17 - 39 y 61 50 40 – 59 y 55 47 60 y and older 52 46 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 2
  3. 3. Total body water compartments extracellular fluid ECF ICF intracellular fluid ISF 1/3 2/3interstitial fluid (and lymph) IVF blood plasma 3
  4. 4. Quantification of body fluid compartments (in adult male, 70 kg) Percentage of Fluid Volume (Liters) Body fluid Body weight TBW 42 100 % 60 % ICF 28 67 % 40 % ECF 14 33 % 20 % ISF 10.5 25 % 15 % IVF 3.5 8% 5% (blood plasma) The contribution of lymph and transcellular fluid is negligible. 4
  5. 5. Transcellular fluidsare secreted by specialized cells into particular body cavities• cerebrospinal fluid• intraocular fluid• synovial fluid• pericardial, intrapleural, peritoneal fluids• digestive juices• bile• urinethey are usually ignored in fluid balanceExceptions:heavy vomiting or diarrhea, ascites or exudates may cause fluid imbalances 5
  6. 6. Daily water balance (average data, 70 kg male)Water input Water outputbeverages 1200 ml insensible (skin, lungs) 800 mlfood 1000 ml sweat 100 mlmetabolic water 300 ml feces 100 ml urine 1500 mltotal input 2500 ml total output 2500 mlAttention 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 depletionin the elders: the sensation of thirst is often impaired or lacking 6
  7. 7. Metabolic water 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 + heatExamples 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 7
  8. 8. Average ion concentrations in blood plasma, ISF, and ICF (mmol/l)Ion Blood plasma ISF ICFNa+ 142 142 10K+ 4 4 155Ca2+ 2.5 1.3 tracesMg2+ 1.5 1 15Cl- 103 115 8HCO3- 25 28 10HPO42- + H2PO4- 1 1 65 *SO42- 0.5 0.5 10Organic anions 4 5 2Proteins 2 - 6* Most of them are organic phosphates (hexose-P, creatine-P, nucleotides, nucleic acids) 8
  9. 9. The average molarity of ions in blood plasma Molarity (mmol/l) Molarity (mmol/l)Cation Anion Cation Charge Anion ChargeNa+ 142 142 Cl- 103 103K+ 4 4 HCO3- 25 25Ca2+ 2.5 5 Protein- 2 18Mg2+ 1.5 3 HPO42- 1 2 total positive charge 154 SO42- 0.5 1 OA 4 5 total negative charge 154 65 – 85 g/l Total buffer bases: 42 ± 3 mmol/l 9
  10. 10. 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 × [SO42-] = 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 10
  11. 11. Sodium balance 150-280 mmol/dayInput table salt (NaCl), salty foods (sausages etc.), some mineral waters ECF (50 %), bones (40 %), ICF (10 %)Distribution the main cation of ECF, responsible for osmolality and volume of ECF 130-145 mmol/lBlood level gradient between ECF and ICF is created and maintained by Na+, K+-ATPase aldosterone = salt conserving hormoneRegulation ANP = atrial natriuretic peptide = antagonist of aldosterone 120-240 mmol/day (urine)Output [99 % of filtered Na+ is reabsorbed in kidneys] ~10 mmol/day (stool), 10-20 mmol/day (sweat) 11
  12. 12. 12
  13. 13. Hormones regulating sodiumFeature Aldosterone Atrial natriuretic peptideProduced in adrenal cortex heart atriumChemical type steroid peptide resorption of Na+Main effects excretion of K+ excretion of Na+ and water (in kidneys) 13
  14. 14. The loss of sodium under special or pathological situationsThe loss by urine• diuretics (furosemid, thiazides)• osmotic diuresis (hyperglycemia in diabetes)• renal failure• low production of aldosteroneThe loss by digestion juices• vomiting, diarhea, fistulas etc.The loss by sweating• work or sports in hot and dry conditions 14
  15. 15. Potassium balance 40-120 mmol/dayInput mainly from plant food: potatoes, legumes, fresh and dried fruits, nuts etc. ICF (98 %), ECF (2 %)Distribution the main cation of ICF, associated with proteins (polyanions) and phosphates 3.8-5.2 mmol/l,Blood level the gradient between ECF and ICF is maintained by Na+, K+-ATPase blood level of K+ depends on pH the secretion of K+ into urine (in distal tubule) depends on many factors:Regulation K intake, aldosterone production, alkalosis/acidosis, anions in urine 45-90 mmol/day (urine)Output 5-10 mmol/day (stool) 15
  16. 16. Potassium blood level depends on acid-base status pH = 6.8 ~ 7.0 mmol K+ / l K+ pH = 7.4 ~ 4.4 mmol K+ / l pH pH = 7.7 ~ 2.5 mmol K+ / l cell cell H+ H+ alkalosis →acidosis → H + H+hyperkalemia cation exchange hypokalemia K+ K+ K+ K+ 16
  17. 17. Ion diameter (nm) Ion Free HydratedThe hydration of Na and K cation + + Na+ 0,19 0,52 K+ 0,27 0,46• 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+ K+ 17
  18. 18. The main species determining the osmolality of blood plasma IVF ISF ICF water urea glucose × Na+ × proteins × × barrier: barrier: blood vessel walls cell membrane pore-lined highly selective 18
  19. 19. 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 cellmembranes (about 3 × 109 molecules per second). Aquaporin channel structureAquaporins consist of six membrane-spanning segmenst arranged in two hemi-poreswhich 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 itshigh specifity. 19
  20. 20. In membranes, some of aquaporin types exist as homotetramers, or formregular square arrays.Aquaporins are controlled by means of gene expression, externalization of silenced channelsin the cytoplasmic vesicles, and also by the changes in intracellular pH values (e.g., increasein proton production inhibits water transport through AQP-2 and increases the permeabilityof AQP-6).More than 12 isoforms of aquaporins were identified in humans, 7 of which arelocated in the kidney.Examples:AQP1 (aquaporin-1), opened permanently, is localized in red blood cells, endothelial andepithelial cells, in the proximal renal tubules and the thin descendent limb of the loop ofHenry.AQP2 is the main water channel in the renal collecting ducts. It increases tubule wallpermeability to water under the control of ADH: If ADH binds onto the V2 receptorslocated in the basolateral membrane, AQP2 in the membranes of cytoplasmic vesicles isphosphorylated and exposed in the apical plasma membrane. Reabsorbed water leavescells through AQP3 and AQP4 in the basolateral plasma membrane. 20
  21. 21. males 290 ± 10 mmol/kg H2OOsmolality of blood plasma females 285 ± 10 mmol/kg H2OOsmolality of biological fluids is measured by osmometers based mostly on thecryoscopic principle.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 beenmeasured), it is useful to compare the value with the approximate assessment:osmolality (mmol/kg H2O) ≈ 2 [Na+] + [glucose] + [urea] (mmol/l)An osmotic gap can be perceived in this way. The measured value is higherthan the calculated rough estimate, if there is a high concentrationof 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] 21
  22. 22. DistinguishOsmolarity = i c = i × molarity (mmol/l)Osmolality = i cm = i × molality (mmol/kg H2O) 22
  23. 23. Oncotic pressure – colloid osmotic pressureWithin the extracellular fluid, the distribution of water between bloodplasma and interstitial fluid depends on the plasma protein concentration.The capillary wall, which separates plasma from the interstitial fluid,is freely permeable to water and electrolytes, but restricts the flow of proteins.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.Osmotic pressure of blood plasma: 780 - 795 kPaOncotic pressure of blood plasma: 2.7 - 3.3 kPa2.7 – 1.4 kPa ... sizable edemas, imminent danger of pulmonary edema < 1.4 kPa ... unless albumin is given i.v., survival is hardly possible 23
  24. 24. The significance of oncotic pressureThe capillary wall is permeable for small molecules and water but notpermeable for proteins.The hydrostatic pressure of a blood tends to push water out of thecapillary – filtration.The oncotic pressure pulls the water from the interstitial space backinto the capillary - resorption.Endothelial cellsBlood capillary 24
  25. 25. The movement of fluid between plasma and interstitial fluidOncotic pressure can be measured by means of colloid osmometers. 25
  26. 26. Six cases of water/sodium imbalance The loss of The overload by isotonic fluid isotonic fluid „pure“ water „pure“ water „pure“ sodium „pure“ sodium 26For more details see physiology
  27. 27. The loss of isotonic fluid = isotonic dehydration Typical situationNormal The loss of isotonic fluid vomiting, diarrhea, bleeding, burns,status (ascites)ECF Consequence ↓ ECF volume (hypovolemia)ICF activation of RAAS 27
  28. 28. The loss of pure (solute-free) water/hypotonic fluid = hypertonic dehydration Typical situations Normal hyperventilation The loss of pure water status no drinking (older people) osmotic diuresis ECF ADH deficit (diabetes insipidus) Consequences H2O hypovolemia ICF ECF becomes hypertonic (hypernatremia) water osmotically moves from ICF to ECF cellular dehydration (cells shrink)* ADH production ↑ (water retention)* The shrinking of brain neurons disturbs brain functions (confusion, delirium, convulsions, coma) 28
  29. 29. The loss of pure sodium (salt) Typical situationsNormal The loss of salt aldosterone deficitstatus diuretics (also vomiting, sweating, diarrhea) . .ECF Consequences . . . . ECF becomes hypotonic (hyponatremia) H2O water osmotically moves from ECF to ICF →ICF hypovolemia + intracellular edemas expansion of ICF → increase of intracranial pressure - imminent danger of cerebral edemas ADH production ↓ (water excretion) + RAAS activation 29
  30. 30. The overload by isotonic fluid = isotonic hyperhydration Typical situationsNormal The overload by excessive infusions by isotonic salinestatus isotonic fluid cardial insufficiency renal diseasesECF (secondary hyperaldosteronism) Consequences expansion of ECF volumeICF ECF edema 30
  31. 31. The overload by pure (solute-free) water/hypotonic fluid = hypotonic hyperhydration (water intoxication) Typical situations Normal The overload by water excessive drinking simple water status SIADH*, also stress, trauma, infections . . . . gastric lavage ECF . . . . . excessive infusion of glucose solution H2O Consequences ICF ECF volume expansion ECF becomes hypotonic (hyponatremia) water moves osmotically to ICF ICF + ECF edemas ADH production ↓ (water diuresis) * syndrome of inappropriate ADH 31
  32. 32. The overload by pure sodium/salt Typical situations excessive intake of salt / mineral watersNormal The overload by sodium drinking sea water (ship wreck)status excessive infusions of Na-salts (ATB ...) aldosterone hyperproductionECF Consequences H2O ECF becomes hypertonic (hypernatremia) → hypervolemiaICF water moves osmotically from ICF to ECF ECF (pulmonary) edemas + cellular dehydration ↑ ADH (to retain water) ↑ ANP / urodilatin (to excrete sodium) RAAS inhibited 32
  33. 33. Water and osmolality controlAntidiuretic hormone (ADH, Arg-vasopressin, AVP) released from the nerve terminals in posterior pituitaryAldosterone secreted from the zona glomerulosa of adrenal cortex after activation of the renin-angiotensin systemNatriuretic peptides (ANP, BNP) secreted from some kinds of cardiomyocytes in heart atria and chambers 33
  34. 34. Example Water and osmolality control is closely inter-related INTAKE OF Na+ WATER LOSS Osmolality increase Decrease in ECF volume Filling of heart Filling of arteries upper chambers OSMOSENSORS VOLUMOSENSORS hypothalamus liver heart juxtaglomerular cells Secretion of renin Increase of HMV Sensation Secretion of Secretion of of thirst ADH (vasopressin) aldosterone Better filling of arteries Renal WATER INTAKE RETENTION OF WATER RETENTION OF Na+ Antagonistic action of 34 natriuretic peptides ANP and BNPFor details see physiology
  35. 35. Antidiuretic hormone (ADH, Arg-vasopressin, AVP)is a nine amino acid cyclic peptide: Cys–Tyr–Phe–Gln–Asn–Cys–Phe–Arg–Gly S SVasopressin receptors V2 are in the basolateral membranes of renal collectingducts.Vasopressin receptors V1 are responsible for the vasoconstriction. 35
  36. 36. The renin-angiotensin aldosterone system (RAAS) Fluid volume decrease ANGIOTENSINOGEN Blood pressure decrease(blood plasma α2-globulin, >400 AA) Blood osmolality decrease renin THE JUXTAGLOMERULAR CELLS Protein (a proteinase) of the renal afferent arterioles release into the blood ANGIOTENSIN I (a decapeptide) angiotensin-converting enzyme His-Leu (ACE, a glycoprotein in the lung, endothelial cells, blood plasma) ANGIOTENSIN II (an octapeptide) Stimulation of ALDOSTERONE production ANGIOTENSIN III in zona glomerulosa cells of adrenal cortex Vasoconstriction of arterioles Rapid inactivation by angiotensinases 36
  37. 37. Angiotensin II and III N-Terminal sequence of the plasma α2-globulin angiotensinogen:NH2–Asp–Arg–Val–Tyr–Ile–His-Pro–Phe–His–Leu–Leu–Val–Tyr renin Decapeptide angiotensin I:NH2–Asp–Arg–Val–Tyr–Ile–His-Pro–Phe–His–Leu angiotensin 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 37
  38. 38. Aldosterone acts on gene expression levelInduces the synthesis of Na / K channels, and Na/K-ATPase Tubular lumen Blood plasma Aldosterone 3 Na+ 2 K+ Natriuretic Na+ Na+ peptides ATP K+ K+ blood aquaporin 3 H2O H2O aquaporin 2 0 receptors V2 for ADH urine 38
  39. 39. Natriuretic peptides (more types are known) atrial natriuretic peptide (ANP) brain natriuretic peptide (BNP) (mainly of cardiac ventricular origin)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 haveshort biological half-lives. Released N-terminal sequences are inactive, butbecause they are long-lived, their determination is useful. 39
  40. 40. Natriuretic peptides are antagonists of aldosteroneBoth 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 cortexThese peptides are viewed as protectors against volume overload andas inhibitors of vasoconstriction (e.g. during a high dietary sodium intake).Membrane receptors for natriuretic peptides are of unique kind –they exhibit intrinsic guanylate cyclase activity;binding of natriuretic peptides onto receptors increases intracellularconcentration of cGMP. 40