Disturbances of water and mineral balance. Edema Water Balance Children under 1 year: 65-75% of body weight H2O Young men: 60-65% of body weight Young women: 50-55% of body weight A man over 60 years: 50% of body weight In obese individuals, the water forms a smaller percentage than in thin Women over 60 years: 45% of body weight Water content in the body ECF 20-23% (15 liters) TBW 60-65% (45 liters) ECF/ICF=1/2 ICF 40-45% (30 liters) Plasma 4% (3 liters) ISF 16% (12 liters) Plasma/IST=1/4 Liquids Metabolism 1l 0,5 l Food 1l deficit Feeling thirsty Daily water balance Urine 1-2 l Respiration Stool Perspiration 0,5 l 0,6-0,8 l 0,1 l surplus The excretion of urine Major ions ICF (intracelluar fluid) ECF (extracellular fluid) 4,3 mmol/l K+ 140 mmol/l K+ 140 mmol/l Na+ 12 mmol/l Na+ 104 mmol/l 3 mmol/l Cl- Cl- 24-27 mmol/l HCO3 - 10 mmol/lHCO3- The balance of sodium and chloride Food 50-350 mmol Daily sodium balance Urine 50-350 mmol Stool 10 mmol Sweat 10 mmol Food 50-350 mmol Daily balance of chloride Urine 50-350 mmol Stool 10 mmol Sweat 10 mmol Osmotic balance in body fluids Osmotic pressure is related to the concentration of all dissolved particles P1 >== P2 C 1 > C2 H2O H2O H2O H2O [H2O]1 <= [H2O] 2 Osmotic pressure is related to the concentration of dissolved particles relative to the weight of the solvent: osmolality (mmol/kg solvent) the volume of solution : osmolarity (mmol/l solution). Hyperosmolality Hyperosmolarity Hyposmolality Hyposmolarity H2O H2O H2O H2O H2O H2O H2O Isotonic environment Cell 290 ± 10 mmol/l Blood-vessel Interstitial fluid Hypertonic environment Cell H2O > 300 mmol/l H2O Blood-vessel Interstitial fluid Hypertonic environment Cell > 300 mmol/l Hypertonic environment Céva Intersticium Isotonic environment Cell 290 ± 10 mmol/l Blood-vessel Interstitial fluid Hypotonic environment Cell H2O < 280 mmol/l H2O Blood-vessel Interstitial fluid Hypotonic environment Cell < 280 mmol/l Blood-vessel Interstitial fluid Hyperosmolarity due to the Isotonic rise of environment blood urea Cell Total 290 ±osmolarity 10 mmol/l> 300 Blood-vessel Effective osmolarity = Total osmolarity – urea concentration Interstitial fluid The balance of the capillary and its disorders (water and soluti movement between plasma and interstitium) Isotonic environment Cell 290 ± 10 mmol/l Blood-vessel Interstitial fluid Lymphatic drainage Movement of the filtrate proteins Interstitial fluid Oncotic pressure gradient Precapillary sphincter Capillary venule proteins Lymphatic drainage arteriole Lymphatic drainage Accumulation filtrate in the interstitium proteins Interstitial fluid Oncotic pressure gradient Increase hydraulic pressure gradient Congestion in right cardiac insufficiency Precapillary sphincter Capillary venule proteins Lymphatic drainage arteriole Lymphatic drainage Swelling proteins Increased interstitial counterpressure Interstitial fluid Oncotic pressure gradient Increase hydraulic pressure gradient Congestion in right cardiac insufficiency Precapillary sphincter Capillary venule proteins Lymphatic drainage arteriole Lymphatic drainage Movement of the filtrate proteins Interstitial fluid Oncotic pressure gradient Decrease of oncotic pressure gradient Precapillary sphincter Capillary venule proteins Lymphatic drainage arteriole Reduced lymphatic drainage proteins The accumulation of proteins in the interstitium Accumulation filtrate in the interstitium Interstitial fluid Decrease of oncotic pressure gradient Precapillary sphincter Decrease of plasma proteins concentration Capillary venule proteins Lymphatic drainage arteriole Reduced lymphatic drainage proteins The accumulation of proteins in the interstitium Swelling Increased interstitial counterpressure Interstitial fluid Decrease of oncotic pressure gradient Precapillary Prekapilární sphincter sfinkter Decrease of plasma proteins concentration Capillary venule proteins Lymphatic drainage arteriole Lymphatic drainage Inflammation Movement of the filtrate proteins Interstitial fluid Oncotic pressure gradient Dilation of capillaries Precapillary sphincter Capillary venule proteins Lymphatic drainage arteriole Lymphatic drainage Inflammation Accumulation filtrate in the interstitium proteins Interstitial fluid Increase of hydraulic capillary pressure Oncotic pressure gradient Dilation of capillaries Precapillary sphincter Capillary venule proteins Lymphatic drainage arteriole Accumulation of macromolecular products of inflammatory reactions Inflammation Accumulation filtrate in the interstitium proteins Interstitial fluid Increase of hydraulic capillary pressure Reduction of oncotic pressure gradient Dilation of capillaries Increased capillary permeability Precapillary sphincter Capillary venule proteins Lymphatic drainage arteriole Accumulation of macromolecular products of inflammatory reactions Inflammation Accumulation filtrate in the interstitium proteins Interstitial fluid Increase of hydraulic capillary pressure Reduction of oncotic pressure gradient Dilation of capillaries Increased capillary permeability Precapillary sphincter Capillary venule proteins Lymphatic drainage arteriole Accumulation of macromolecular products of inflammatory reactions Inflammation Swelling proteins Increased interstitial counterpressure Reduction of oncotic pressure gradient Interstitial fluid Increase of hydraulic capillary pressure Dilation of capillaries Increased capillary permeability Precapillary sphincter Capillary venule proteins Lymphatic drainage arteriole Control volume and osmolarity Control volume related to regulation of circulating blood volume and thus with hemodynamics (particularly with the regulation of arterial pressure) Therefore, we are talking about so-called "effective circulating volume" Volume - is detected by atrial tension in the wall (low-pressure baroreceptors), by tension in the artery wall and in the glomus caroticus the aortic arch (highreceptors) Osmolarity – is detected by osmoreceptors in the hypothalamus and possibly also liver Control volume and osmolarity closely related to regulation of sodium excretion (sympaticus, aldosterone, ANF) and control urine osmolarity (ADH) Feeling thirsty Osmoreceptors ADH Effective circulating volume Sympathetic and parasympathetic Low pressure baroreceptors High pressure baroreceptors atrial rate The tension in atrial wall Atrial natriuretic faktor NaCl delivery to macula densa High pressure baroreceptors in vas afferens Angiotensinogen Aldosterone Angiotensin III Renin Angiotensin I Angiotensin II pressure rise pressure drop + nucleus paraventricularis + Nausea, vomiting Plasma osmolarity Low pressure baroreceptors osmoreceptors + + + High pressure baroreceptors Angiotensin II Hypoxia hypoglycemia Dopamin + Enkephalin glucocorticoids ? Liver osmoreceptors - + nucleus supraopticus - - - Alcohol ADH ADH [pg/ml] 10 Hypovolemia Hypervolemia 5 Plasma osmolarity 265 270 275 280 285 290 295 300 [mOsm/l] Feeling thirsty at normal volume The feeling of thirst in hypovolemia 15 ADH is mainly regulated by osmolarity, less by volume ADH [pg/ml] 10 5 b -10% -20% -30% Decrease of the effective circulating volume at normal osmolarity + Na excretion in the kidney Na+ Decreased effective circulating volume Sympathetic activity Renin GFR Angiotensin I Na+ resorption Lungs Heart Na+ resorption Na+ resorption Atrial Natriuretic Faktor H2O resorption Adrenal cortex Brain ADH Angiotensin II H2O a Na+ excretion Aldosterone Na+ Euvolemia Delivery Na+ Euvolemia ECF Volume Delivery Effective circulating volume Delivery Na+ Increased effective circulating volume Sympathetic activity Renin GFR Angiotensin I Na+ resorption Lungs Heart H2O resorption Na+ resorption Atrial Natriuretic Faktor H2O resorption Adrenal cortex Brain ADH Angiotensin II H2O a Na+ excretion Aldosterone Na+ Euvolemia Delivery Na+ Euvolemia ECF Volume Delivery Effective circulating volume Delivery Na + + b-intercalar cells -intercalar cells Principal cells K Cl - HCO3 Cl H - + Cl - Aldosterone + + + CO2 - HCO3 + Na -K ATPase Cl - karboanhydrase OH + H -ATPase - H H2O Na + + K H + H2O + OH + - karboanhydrase H -ATPase - HCO3 CO2 + - + + + Na Cl - + + H K - - HCO3 2- lumen HPO4 Cl - NH3 + - HCO3 CO2 - H2PO4 + NH4 Cl (titratable acids) Cl - Question Why in healthy people with reducing the volume of extracellular fluid and subsequent activation of renin-angiotensin-aldosterone system are not lost potassium? Stimulus: + + Effective circulating volume Na+ reabsorption (proximal tubule) Aldosterone + +secretion + secretion KK (collecting ducts) Does not change Flow rate of urine in the tubule Reabsorption of Na+ (collecting ducts) + Effective circulating volume Stimulus: 1. diuretics 2. osmotic diuresis + Na+ reabsorption (proximal tubule) Aldosterone + K+secretion (collecting ducts) + Flow rate of urine in the tubule Reabsorption of Na+ (collecting ducts) Question What is the regulatory importance of atrial natriuretic factor? ANF acts as a safety valve when the compensatory increase in circulating blood volume Heart failure Cardiac output Effective circulating volume Activation of renin-angiotensin-aldosterone system Congestion - increase in secondary capillary pressure Moving water from intravazálního into the interstitial space The regulatory response to approximately 100 minutes Water retention in the kidneys Venous filling Heart filling in diastole Reply to approximately 4 minutes The safety valve! ANF Osmolarity disorders Transfers of water between the ICF and ECF a) Cells in the hypertonic environment H2O Osmotic shift of water from cells Reducing the volume of cells a) Cells in the hypertonic environment H2O Osmotic shift of water from cells Reducing the volume of cells H2O Active increase in osmotic pressure in the cell and subsequent transfer of water Cell volume increases slightly Na Organic osmoles + H + Na - + - Cl + H HCO3 - Cl H2CO3 CO2 H2O - Hypertonic cell environment HCO3 H2O - + K 2Cl + Na Responding cells - income soluti Rise of intracellular osmolarity Suck in water H2O Normal brain cell volume Skull Raise the PNa Herniate Increased brain volume H2O Organic osmoles K+ + AOrganic osmoles K+ + A- Rapid fall in the PNa K+ + A - H2O Organic osmoles K+ + ASlow fall in the PNa H2O H2O Blood vessels Organic osmoles Brain cell volume ist almost normal H2O Shrunken brain cells; stretched blood vessel may rupture Adaptive changes Organic osmoles K+ + AOrganic osmoles K+ + A- b) Cell in hypotonic environment H2O Osmotic movement of water into the cell Increasing the volume of cells b) Cell in hypotonic environment H2O Osmotic movement of water into the cell Increasing the volume of cells H2 O Active reduction of osmotic pressure in the cell and subsequent transfer of water Cell volume is somewhat reduced Hypotonic cell environment + K - Cl + K - Cl - + Cl + K K - Cl Organic osmoles H2O Responding cells - Loss of soluti Loss of soluti Decrease in osmolarity Water loss H2O Normal brain cell volume Skull Osmotic demyelinisation due to cell volume shrinkage H2O Acute fall in PNa H2O Organic osmoles K+ + A Slow rise in the PNa H2O Organic osmoles K+ + A- H2O H2O Swollen brain cells and higher intracranial pressure Adaptive changes Rapid rise in the PNa K+ + A- Organic osmoles Brain cell volume ist almost normal Organic osmoles K+ + AOrganic osmoles K+ + A- Disorders of the volume and osmolarity Itravascular fluid • hypovolemia shock • hypervolemia Renal failure and water intake Extravascular fluid Dehydratation hypertonic isotonic hypotonic Hyperhydratation hypotonic isotonic (hypertonic) Clinical signs Hct, Hb, Plasma Na+ Tot.pl.prot. PlasmOsm. Dehydratation hyperosmotic isoosmotic normoosmotic ↑ Hyperhydratation ↓ hypoosmotic isoosmotic hyperosmotic MCV ↑ normal ↓ ↓ normal ↑ ↓ normäl ↑ ↑ normal ↓ Dehydratation Euvolemia • Hypotonic (hypoosmolar) • Isotonic – normal fysiology state • Hypertonic (hyperoosmolar) Dehydratation Water retention Water loss volume Water retention • Hypotonic (hypoosmolar) • Isotonic (isoosmolar) • Hypertonic (hyperosmolar) Soluti retention Hyperhydratation • Hypotonic (hypoosmolar) • Isotonic (isoosmolar) • Hypertonic (hyperosmolar) osmolarity Water loss Soluti loss Isotonic dehydratation ECT ICT Cause: loss of isotonic fluid (the same loss of water soluti) Initial state Loss of isotonic fluid from the ECF does not displace the water between the ICF and ECF Solutes H2O Isotonic hyperhydratation ECT Cause: isotonic fluid retention (the same water retention and soluti) Soluti H2O ICT Initial state Retention of isotonic fluid from the ECF does not displace the water between the ICF and ECF Hypotonic dehydratation ECT ICT Cause: The greater solute loss than water loss Solutes H2O Initial state H2O Start failure Osmotic equilibriumincreasing volume of ICF The active changes in cellular osmolarity occurs mainly in brain tissue Compensatory reduction in osmolarity in ICF ... H2O leads to a shift of water from ICF ... …and to correction of increased volume of ICT Hypertonic dehydratation Cause: more water loss than the solute loss Solutes H2O ECT ICT Initial state H2O Start failure Osmotic equilibrium, reducing the volume of ICF The active changes in cellular osmolarity occurs mainly in brain tissue Compensatory increase in osmolarity in ICF ... H2O …leads to water movement in ICF ... …and to correction of reduced volume of ICT Hypertonic hyperhydratation Cause: more soute retention than water retention Solutes H2O ECT ICT Initial state H2O Start failure Osmotic equilibrium, reducing volume of ICF The active changes in cellular osmolarity occurs mainly in brain tissue Compensatory increase in osmolarity in ICF... H2O …leads to water movement in ICF ... ... and to correction of reduced volume of ICF Hypotonic hyperhydratation Cause: The greater water retention than soluti retention Solutes H2O ECT ICT Initial state H2O Start failure Osmotic equilibriumincreasing volume of ICF The active changes in cellular osmolarity occurs mainly in brain tissue Compensatory reduction in osmolarity of the ICF ... H2O leads to a shift of water from ICF ... and to correction of increased volume of ICF Isotonic hyperhydratation ECT ICT Initial state Solutes H2O H2O Edema Congestive heart failure Cardiac output Cirrhosis of the liver Nephrotic syndrome Ascites Albumin Albumin Capillary pressure Transfer of fluid from intravascular space ino ISF Effective circulating volume Sympathetic Renin - angiotensin - aldosterone Na+ reabsorption in the kidney Edema (hyperhydration) Primary renin Primary aldosterone Primary renal disease Angiotensin 2 Aldosteron Glomerular filtration Primary Na+ reabsorpce Na+ reabsorption Na+ and water retention in the kidneys Edema, hypertension (hyperhydratation) Causes of hyperosmolarity Causes hyposmolarity H2O solutes solutes H2O Solutes retention (relative or absolute) Water deficit Solutes deficit Water retention (relative or absolute) hypernatremia normonatremia (140 mmol/l) hyponatremia Na+ Na+ Na+ Na+ Na+ H2O H2O H2O H2O hypovolemia (dehydratation) Na+ Na+ H2O H2O isovolemia Na+ Na+ H2O H2O H2O hypervolemia hypernatremia hyponatremia Na+ Plasma Na+ concentration normonatremia (140 mmol/l) Na+ Na+ Na+ Na+ H2O H2O H2O H2O Extracellular dehydratation Na+ Na+ H2O H2O Na+ Na+ H2O H2O H2O Extracellular edema + K - main itracellular cationt Potassium and Acid-Base K+mmol/l 8 7 6 B 5 H+ H+ K+ K+ A 4 C 3 D 2 1 A: Norm 6,9 7,0 7,1 7,2 7,3 7,4 7,5 7,6 7,7 7,8 pH H+ K+ H+ H+ H+ K+ K+ K+ B: Acidemia exchange K+ / H+ K+ K+ C: long lasting acidemia K+ depletion H+ H+ K+ K+ D: K+ Rapid alkalinization H+/K+ - dangerous hypokalemia K+ Normal or increased intake of potassium From 10% to 50% from 5% to 30% K+ Potassium depletion Normal or increased intake of potassium From 10% to 50% from 5% to 30% Na + + b-intercalar cells -intercalar cells Principal cells K Cl - HCO3 Cl H - + Cl - Aldosterone + + + CO2 - HCO3 + Na -K ATPase Cl - karboanhydrase OH + H -ATPase - H H2O Na + + K H + H2O + OH + - karboanhydrase H -ATPase - HCO3 CO2 + - + + + Na Cl - + + H K - - HCO3 2- lumen HPO4 Cl - NH3 + - HCO3 CO2 - H2PO4 + NH4 Cl (titratable acids) Cl - Potassium depletion Large delivery of sodium in CCD (e.g. in osmotic diuresis) Low chloride in CCS Catabolism Long lasting acidemia Hyperaldosteronism Diuretics (Furosemid) K+ K+ K+ H+ H+ Intracellular acidosis in proximal tubule Enhanced resorption HCO3- Enhanced resorption Cl- Effect of hypokalemia on ECF volume ECF Enhanced resabsorption Cl- Potassium retention Oliguric phase of acute renal failure Tubular damage (e.g. interstitial nephritis, diabetic nephropathy) Hypoaldosteronism (m. Addisoni) K+ K+ Vomiting Normal state HCO3- Stomach H+ CO2 Cl- Balanced CO2 H2O H2O Cl- No acid-base changes - H+ Cl HCO3- H+ CO2 H2O Duodenum and pancreas Hypertonic dehydratation Chloride H+ loss Cl- H+ loss Hypotonic fluid loss HCO3- Stomach H+ HCO3retention Vomitoing HCO3CO2 Cl- Unbalanced CO2 H2O H2O Cl- Hypochloremic alkalosis - H+ Cl HCO3- H+ CO2 H2O Duodenum and pancreas + Na Cl Primary cause: Losses of Cl- a H+ by vomiting Glomerular filtraton (norm) - Cl - Glomerulal filtration (hypochloremic alkalosis) + Na Depletion of Cl chlorides + H Readsorbtion of sodium and chlorides Metabolic alkalosis + Na Cl + Remnant of sodium is exchanged with + and H+ K + Na+/Clreabsorbtion is diminished H + K + Na Cl + H + K Increased exchange Na+ with K+ and Na+ with H+ + Intracellular fluid K Potassium depletion + Na Na + H H + K H+ NH4+ + + + H K Paradoxal urine acidification Increases lossse ofn + K Excretion of potassium increases, acidification of + urine regardless of alkalosis H Diarrhoea Normal state: reabsorbiton NaCl + water in colon H2O CO2 + H2O ClH+ Na+ HCO3AE NHE Na+ H+ Cl- HCO3- H+ HCO3CO2 + H2O Na+ Cl- H2O Increased delivery (H2O, Na+, Cl-) to colon H2O CO2 + H2O ClH+ Na+ HCO3- NHE Na+ AE H+ Cl- HCO3- H+ Increased NHE and AE transport HCO3CO2 + H2O Na+ Cl- H2O Delivery (H2O, Na+, Cl-) to colon is higher then capacity of colon reabsorbtion -> diarhoea H2O H2O Na+ CO2 + H2O ClH+ Na+ HCO3 HCO3- - AE NHE Na+ K+ H+ Cl- HCO3- H+ AE has a lager capacity then NHE HCO3CO2 + H2O H2O Na+ ClCl- HCO3- Hypotonic fluid loss HCO3Hyperchloremic acidosis Alkalic diarrhoea Hypertonic dehydratation Potassium loss HCO3- Hypotonic fluid loss Hyperchloremic acidosis Hypertonic dehydratation Severe alkalic diarrhoea Acute volume changes and acid-base disturbances Normal state HCO3 - CO2 TA + NH4+ H2CO3 CO2 balance + H2O H H+ balance HBuf Buf - Dilution HCO3 - CO2 TA + NH4+ H2CO3 CO2 balance + H2O H H+ balance Buffers system acid-base disturbances: Dilutional acidemia HBuf Buf - Dilution CO2 equilibrium shift HCO3 TA + NH4+ H2CO3 CO2 balance + H2O H H+ balance Buffers system acid-base disturbances: Dilutional acidemia HBuf Buf - Normal state HCO3 - CO2 TA + NH4+ H2CO3 CO2 balance + H2O H H+ balance HBuf Buf - Hemoconcentration CO2 HCO3 TA + NH4+ H2CO3 CO2 balance + H2O H H+ balance Buffers system acid-base disturbances: Contractional alkalemia HBuf Buf - Hemoconcentration CO2 equilibrium shift HCO3 TA + NH4+ H2CO3 equilibrium shift CO2 balance + H2O H H+ balance Buffers system acid-base disturbances: Contractional alkalemia HBuf Buf -