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Integrative Physiology

Integrative Physiology. O2/CO2 transport disorders. Respiratory disorders. Circulation disorders. Acid -Base disorders. Acid -Base disorders. Osmolarity disorders. Electrolyte disorders. Volume disorders. Gastrointestinal disorders. Kidney disorders.

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Integrative Physiology

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  1. IntegrativePhysiology O2/CO2 transport disorders Respiratorydisorders Circulationdisorders Acid-Base disorders Acid-Base disorders Osmolarity disorders Electrolytedisorders Volume disorders Gastrointestinaldisorders Kidneydisorders

  2. Homeostasis of internal enviroment Disorders of the acid-base chemistry, influence of respiration, lungs and altered metabolism

  3. Inputs Balance between input and output flow Storage ? Outputs retention ? depletion

  4. External environment of organism Balance estimation Concentrations extracellular fluid - ECF intracellular fluid - ICF Metabolism

  5. External environment of organism Balance estimation Concentrations plasma Lymph capillaries extracellular fluid -ECF interstitial fluid - ISF intracellular fluid - ICF Metabolism

  6. External environment of organism intravascular blood cells plasma Lymph fluid (part of ICF) capillaries capillaries extracellular fluid -ECF interstitial fluid - ISF intracellular fluid - ICF Metabolism

  7. External environment of organism intravascular blood cells plasma Lymph fluid (part of ICF) extracellular fluid -ECF capillaries capillaries transcellular fluid interstitial fluid - ISF intracellular fluid - ICF Metabolism

  8. External environment of organism GIT Lungs „exchangers“ Kidney intravascular blood cells plasma Lymph fluid (part of ICF) extracellular fluid -ECF capillaries transcellular fluid interstitial fluid - ISF intracellular fluid - ICF Metabolism

  9. External environment of organism „exchangers“ GIT Lungs Kidney intravascular blood cells plasma Lymph fluid (part of ICF) extracellular fluid -ECF Circulation capillaries „mixing“ transcellular fluid interstitial fluid - ISF intracellular fluid - ICF Metabolism

  10. External environment of organism GIT Lungs „exchangers“ Kidney intravascular blood cells plasma Lymph fluid (part of ICF) extracellular fluid -ECF Circulation capillaries „mixing“ transcellular fluid interstitial fluid - ISF intracellular fluid - ICF Metabolism

  11. External environment of organism CO2 H+ GIT Lungs „exchangers“ Kidney intravascular blood cells plasma Lymph fluid (part of ICF) extracellular fluid -ECF Circulation capillaries „mixing“ transcellular fluid interstitial fluid - ISF intracellular fluid - ICF ACID-BASE BALANCE Metabolism

  12. Practically complete reabsorbtion of HCO3- H+ excretion Acid-Base Balance 60 mmol/24 h CO2 HCO3- H2CO3 TA+NH4+ H+ H2O A- 20 000 mmol/24 hod 60 mmol/24 hod Metabolic production of CO2 Metabolic production od strong acids

  13. Buffering systems of the blood + + CO2 H2O H2CO3 H+ HCO3- HBuf H+ + Buf- H+ + Hb- HHb H+ + Alb- HAlb H+ + HPO42- H2PO4- non-bicarbonate buffers Buf = Hb + Alb + PO4-

  14. HCO3- CO2 H2CO3 H2O H+ HBuf Buf- Buffering reactions

  15. AcidBalance BaseBalance Acid-Base Balance Productionof HCO3- Productionof H+ Diet -> 2H++SO42- Diet ->H+ + HPO4- Diet -> 3K++ 3 HCO3- Removalof H+ Removalof HCO3- 2H++2HCO3- -> 2CO2+2H2O Glucose -> 3H++Citrate- Excreteorganicanions Add „new“ HCO3- 2NH4++SO4- H2PO42- 3K++Citrate- Urine

  16. H+formation/removal Reactionsthatyields H+ (more negative charge in productsthan in substrates) Glucose -> Lactate- + H+ C16fattyacids-> 4ketoacidsanions- + 4 H+ Cysteine -> urea + CO2+H2O+SO42- + 2 H+ Lysine+ -> urea + CO2 + H+ Reactionsthatremoves H+ (more net positive charge in productsthan in substrates) Lactate- + H+-> Glucose • Glutamate- + H+-> urea + CO2+H2O • Citrate- + 3 H+-> CO2+H2O H+ are neitherproduced nor removed(neutrals to neutrals) • Glucose -> Glycogenor+ CO2+H2O • Triglyceride -> CO2+H2O • Alanine -> urea + glucoseorCO2+H2O

  17. Diet ECF 2CO2+2H2O 2 H+ Sulfur-AA 2 HCO3- SO42- urine Glutamine SO42- 2NH4+ 2NH4+ kidney ECF Diet H+ CO2+H2O HCO3- RNA-P- HPO42- CO2+H2O urine kidney HPO4- H+

  18. liver Diet OA utilisation Glucose OA- ECF HCO3- OA- H+ H+ K+ CO2+H2O CO2+H2O K+ OA- OA- kidney urine

  19. Acid-base regulation - CO2 HCO3 TA + NH4+ H2CO3 CO2 balance H2O H+ H+ balance • Buffer systems (msec) • Respiration control (12 hours) • Kidney control (3-5 days) HBuf Buf - Exchange H+/K+ H+/Na+ between cells and ECF Role of liver in AB regulation

  20. Acid-base disturbances: - CO2 HCO3 TA + NH4+ H2CO3 CO2 balance H2O H+ H+ balance HBuf Buffer system acid-base disturbances Buf - Balance acid-base disturbances: - metabolic acidosis/alkalosis - respiration acidosis/alkalosis

  21. - CO2 HCO3 TA + NH4+ H2CO3 CO2 balance H2O H+ H+ balance HBuf • Buffers system acid-base disturbances: • Dilutional acidemia • Contractional alkalemia • Hypoproteinemic alkalemia Buf -

  22. Dilution - CO2 HCO3 TA + NH4+ H2CO3 CO2 balance H2O H+ H+ balance HBuf • Buffers system acid-base disturbances: • Dilutional acidemia Buf -

  23. Dilution equilibrium shift - CO2 HCO3 TA + NH4+ H2CO3 CO2 balance H2O H+ H+ balance HBuf • Buffers system acid-base disturbances: • Dilutional acidemia Buf -

  24. Hemoconcentration - CO2 HCO3 TA + NH4+ H2CO3 CO2 balance H2O H+ H+ balance HBuf • Buffers system acid-base disturbances: • Contractional alkalemia Buf -

  25. Hemoconcentration CO2 - HCO3 TA + NH4+ H2CO3 CO2 balance H2O H+ H+ balance HBuf • Buffers system acid-base disturbances: • Contractional alkalemia Buf -

  26. Hemoconcentration CO2 - HCO3 equilibrium shift TA + NH4+ H2CO3 CO2 balance H2O H+ H+ balance HBuf • Buffers system acid-base disturbances: • Contractional alkalemia Buf -

  27. Acute hypoproteinemia - CO2 HCO3 TA + NH4+ H2CO3 CO2 balance H2O H+ H+ balance HBuf Buffers system acid-base disturbances: Hypoproteinemic alkalemia Buf -

  28. Acute hypoproteinemia - CO2 HCO3 TA + NH4+ H2CO3 equilibrium shift CO2 balance H2O H+ H+ balance HBuf Buffers system acid-base disturbances: Hypoproteinemic alkalemia Buf -

  29. Acid-base disturbances: - CO2 HCO3 TA + NH4+ H2CO3 CO2 balance H2O H+ H+ balance HBuf Buffer system acid-base disturbances Buf - Balance acid-base disturbances: - metabolic acidosis/alkalosis - respiration acidosis/alkalosis

  30. PCO2torr 90 pH=7,1 pH=7,2 pH=7,37 pH=7,3 pH=7,43 80 pH=7,5 Sustained respiratory acidosis Acute respiratory acidosis 70 pH=7,6 60 Sustained metabolic alkalosis 50 Akute metabolic alkalosis Acute metabolic acidosis 40 30 Sustained metabolic acidosis Acute respiratory acidosi Sustainedrespiratoryalkalosis 20 10 -20 -15 -10 15 -5 -25 25 0 30 10 5 20 Base Excessmmol/l

  31. Bicarbonate reabsorbtion (4) diarhoea TA+NH4 + (3) losses of HCO3- (1) Increased metabolic production of strong acids (2) Disorder of H+ excretion H+excretion CO2 HCO3- H2CO3 H+ retention H+ depletion H+ H2O HBuf A- Buf -

  32. Gastrointestinal losses of bicarbonate NH3 • Metabolic acidosis with: • increased anion gap • normal anion gap H+ A- HCO3- Cl- H+ Accumulation of anions of strong acids (laktate acidosis ketoacidosis uremic acidosis) Cl- NH4+ Cl- Urea Overdosis of NH4Cl K+ Na+ Normal anion gap Anion gap Na+ Increased anion gap Na+ Na+ In urine: [K+]+[Na+]-[Cl-] < 0 HCO3- HCO3- HCO3- Cl- Relativeaccumulationofchlorides Cl- NH3 Cl- Cl- HCO3- HCO3- H+ Decreasedacidification (tubularacidosis, hypoaldosteronisms, decreasesglomer. filtration) HCO3- Cl- NH4+ K+ Cl- Na+ in urine: [K+]+[Na+]-[Cl-] >= 0

  33. Diarrhoea

  34. Cl- Na+ H+ H20 + CO2 HCO3- H2O H2O NHE AE Colon H+ Na+ HCO3- Cl- H20 + CO2 HCO3- Na+ Cl- HCO3- H2O

  35. Cl- H+ H20 + CO2 HCO3- HCO3- Na+ Na+ H2O H2O H2O AE NHE Colon H+ Na+ HCO3- Cl- H20 + CO2 HCO3- Hypotonic fluid loss Cl- HCO3- Na+ H2O Hypertonicdehydratation Cl- Alkalic diarrhoea HCO3- Hyperchloremicacidosis

  36. Cl- Cl- H+ H20 + CO2 HCO3- HCO3- Na+ Na+ H2O H2O H2O AE NHE Colon K+ Potassiumloss H+ Na+ HCO3- Cl- H20 + CO2 HCO3- Hypotonic fluid loss Cl- HCO3- Na+ H2O Hypertonicdehydratation Cl- Severe alkalicdiarrhoea HCO3- Hyperchloremicacidosis

  37. Cl- Histidine H.Histidine+ Cl- H20 + CO2 H+ HCO3- Na+ Na+ H2O H2O H2O NHE Colon AE H+ Na+ HCO3- Cl- H20 + CO2 HCO3- Hypotonic fluid loss Na+ Cl- HCO3- H2O Hypertonicdehydratation HCO3- Acidic diarrhoea in DRA, down-regulatedadenoma Cl- Hypochloremicalkalosis

  38. Cl- HCO3- Complete reabsorbtion norm H+ norm Normalacidification proximaltubularrenalacidosis NH4+ Cl- Rateofbicarbonatereabsorbtion NH4+ Cl- b a c K+ normal anion gap Anion gap Na+ Na+ Na+ HCO3- Normalurine anion gap HCO3- In urine: [K+]+[Na+]-[Cl-] < 0 Cl- Plasma levelof HCO3- 20 10 25 15 Cl- NH3 Cl- HCO3- Hyperchloremicacidosiswithnormal anion gap Cl- HCO3- H+ Decreasedacidification (tubularacidosis, hypoaldosteronisms, decreasesglomer. filtration) HCO3- Cl- NH4+ K+ Positive urine anion gap Cl- c b a Na+ norm In urine: [K+]+[Na+]-[Cl-] >0 pH=5,5 pH=6,5 pH=7,8 pH=5,5

  39. Bicarbonate reabsorbtion Metabolicalkalosis TA+NH4 + hyperaldosteronism katabolism (7) K+ depletion (6) vomiting H+ K+ Overdosis HCO3-infusion H+excretion CO2 HCO3- H2CO3 Retence H+ Retence H H+ H2O HBuf A- Buf -

  40. PCO2torr 90 pH=7,1 pH=7,2 pH=7,37 pH=7,3 pH=7,43 80 pH=7,5 Sustainedrespiratoryacidosis Acute respiratory acidosis 70 pH=7,6 60 Sustained metabolic alkalosis 50 Akute metabolic alkalosis Acute metabolic acidosis 40 30 Sustainedmetabolicacidosis Acute respiratory acidosi Sustained respiratory alkalosis 20 10 -20 -15 -10 15 -5 -25 25 0 30 10 5 20 Base Excessmmol/l

  41. Vomiting

  42. HCO3- H+ CO2 Cl- H2CO3 H2CO3 Balanced Stomach CO2 H2O H2O Cl- Cl- H+ +HCO3- H+ H2CO3 CO2 CO2 H2O Duodenum andpancreas

  43. Cl- Hypotonic fluid loss H+ Hypertonicdehydratation HCO3- H+ CO2 Cl- H2CO3 H2CO3 Unbalanced, HCO3-retension Stomach CO2 H2O H2O Cl- hypochloremia Hypochloremicalkalosis Cl- H+ H++HCO3- CO2 H2CO3 CO2 H2O Duodenum andpancreas

  44. Cl- Na+ Na+ Cl- Cl- Remnant of sodium is exchanged with and H+ K+ Na+ Na+ H+ K+ H+ NH4+ Primary cause: Losses of Cl- a H+ by vomiting Glomerular filtraton (norm) Glomerulal filtration (hypochloremic alkalosis) Na+ Na+ Cl- Depletion of chlorides Cl- H+ Na+/Cl- reabsorbtion is diminished Readsorbtion of sodium and chlorides Metabolic alkalosis H+ H+ K+ K+ Increased exchange Na+ with K+ and Na+ with H+ Intracellular fluid K+ Potassiumdepletion H+ Excretion of potassium increases, acidification of urine regardless of alkalosis K+ H+ K+ H+ Paradoxal urine acidification Increases lossse ofn

  45. PCO2torr 90 pH=7,1 pH=7,2 pH=7,37 pH=7,3 pH=7,43 80 pH=7,5 Sustained respiratory acidosis Acute respiratory acidosis 70 pH=7,6 60 Sustained metabolic alkalosis 50 Akute metabolic alkalosis Acute metabolic acidosis 40 30 Sustained metabolic acidosis Acute respiratory acidosi Sustainedrespiratoryalkalosis 20 10 -20 -15 -10 15 -5 -25 25 0 30 10 5 20 Base Excessmmol/l

  46. PCO2torr 90 pH=7,1 pH=7,2 pH=7,37 pH=7,3 pH=7,43 80 pH=7,5 Sustained respiratory acidosis Acute respiratory acidosis 70 pH=7,6 60 Sustained metabolic alkalosis 50 Akute metabolic alkalosis Acute metabolic acidosis 40 30 Sustained metabolic acidosis Acute respiratory acidosi Sustainedrespiratoryalkalosis 20 10 -20 -15 -10 15 -5 -25 25 0 30 10 5 20 Base Excessmmol/l

  47. Arterial blood at pH=7,4 Concentration of O2 Oxygen released due drop PO2 Oxygen released due to shift of dissotiacion curve (Bohr effect) Venose blood at pH=7,2 PO2 PaO2 PvO2

  48. Arterial blood at pH=7,6 (alkalemia) Arterial blood at pH=7,4 (normal conditions) Release of oxygen at respiratory alkalosis Concentration of O2 Release of oxygen at normal condition Venous blood at pH=7,36 (alkalemia) Venous blood at pH=7,2 (normal conditions) Decrease of oxygen delivery to tissues at acute respiratory alkalosis PO2 normal PaO2 PvO2 High PaO2 during hyperventilation at respiratory alkalosis

  49. Mixed acid-base disturbances - examples PCO2torr 90 pH=7,1 pH=7,2 pH=7,37 pH=7,3 pH=7,43 80 pH=7,5 Sustained respiratory acidosis Acute respiratory acidosis 70 pH=7,6 60 Sustained metabolic alkalosis 50 Akute metabolic alkalosis Acute metabolic acidosis 40 30 Sustainedmetabolicacidosis Acute respiratory acidosi Sustained respiratory alkalosis 20 10 -20 -15 -10 15 -5 -25 25 0 30 10 5 20 Base Excessmmol/l Metabolic acidosis + respiratory acidosis Diarrhoea -> metabolic acidosis + vomiting -> metabolic alkalosis + catabolism, ->lactate metabolic acidosis Metabolic acidosis + respiratory alkalosis

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