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acid_base_balance.ppt
The document discusses acid-base metabolism and disorders. It defines key terms like pH, acidosis, and alkalosis. It describes the three major buffer systems that help regulate blood pH - bicarbonate/carbonic acid, phosphate, and protein. The bicarbonate system acts through lungs and kidneys to control CO2 levels. The kidney also regulates pH through reabsorbing bicarbonate, exchanging hydrogen ions for sodium ions, and producing ammonia to excrete excess hydrogen ions in the urine. Together these chemical and organ system mechanisms tightly control blood pH within a narrow range essential for life.
acid_base_balance.ppt
- 1. Physiology and Disorders of Acid-BaseMetabolism Dr. Sarita Mangukiya ASSISTANT PROFESSOR BIOCHEMISTRY, GMCS
- 2. Definitions • Acid –Proton donor • Base – Proton acceptor • pH – Negative log of H+ activity • Acidemia – Arterial blood pH < 7.35 • Alkalemia – Arterial blood pH > 7.45 • Acidosis and Alkalosis – Pathological states leading to acidemia and alkalemia
- 3. 3 pH refers toPotential Hydrogen Expresses hydrogen ion concentration in water solutions Water ionizes to a limited extent to form equal amounts of H+ ions and OH- ions H2O H+ + OH- H+ ion is an acid OH- ion is a base pH SCALE
- 4. 4 H+ ion isan acid
- 5. 5 OH- ion isa base
- 6. 6 H+ ion isan acid OH- ion is a base
- 7. 7 Pure water isNeutral ( H+ = OH- ) pH = 7 Acid ( H+ > OH- ) pH < 7 Base ( H+ < OH- ) pH > 7 Normal blood pH is 7.35 - 7.45 pH range compatible with life is 6.8 - 8.0 OH- OH- OH- OH- OH- OH- H+ H+ H+ H+ OH- OH- OH- OH- OH- H+ H+ H+ H+ OH- OH- OH- H+ H+ H+ H+ H+ H+ H+ ACIDS, BASES OR NEUTRAL??? 1 2 3
- 8.
- 9. Acid – BaseBalance Normal pH of Plasma 7.4 Range 7.35 – 7.45 Production of Acids :- (a)Volatile Acids – 20,000 m.Eq / day - Carbonic Acid (H2CO3) (b) Non Volatile Acids – 60 – 80 m.Eq / day (fixed Acids) - Lactic Acid, Keto Acids, Phosphoric Acids… Production of bases - Very small Amount (Negligible)
- 10. Proton Balance Input (Sourcesof acid) : • Diet – minimal contribution • Metabolism – Volatile acids – CO2 Nonvolatile acids – -- Sulphuric acid -- Phosphoric acid -- Uric acid -- Pyruvic acid -- Lactic acid -- -OH Butyric acid
- 11. Proton Balance Output (Means of disposal) : • Lungs – CO2 • GIT – HCl, HCO3 • Kidney – Free Acid -- Ammonium -- NaH2PO4
- 12. Proton Balance Input Output •Buffersystems •Respiratory regulatory mechanisms •Renal regulatory mechanisms 1st Line of defense Chemical regulatory mechanism 7.35 7.45
- 13. Buffer systems Buffer– mixture of weak acid and a salt of its conjugate base Function – to resist changes in pH when a strong acid or base is added to the solution pK – pH at which a buffer exists in equal proportions of its acid and conjugate base Buffers work best in the interval +/- one pH unit of its pK Buffers are more effective with concentration Buffer value() – amount of base required to change pH by one unit
- 14. Buffer systems Buffer systemActs in pK Bicarbonate/Carbonic acid system Plasma RBC 6.1 Phosphate system RBC Plasma 6.8 Plasma protein system Plasma 7.3 Hemoglobin system RBC 7.3
- 15. Bicarbonate/Carbonic acid buffersystem H+ + NaHCO3- H2CO3 + Na H2O + CO2 HCO3- = regulated by kidney CO2 = regulated by lungs High concentration of conjugate base pK = 6.1. Base : Acid concentration 20 : 1 Disposal/retention of CO2 by lungs / rate of reclamation of HCO3 by renal tubules Respiratory Component Renal Component
- 16. When strong &non volatile acid enters:- e.g. lactic acid NaHCo3 Na+ HCo- 3 HL H+ L- H2Co3 + Na L (Na Lactate) In lung Carbonic Anhydrase H2Co3 H2O + Co2 When alkali enters:- H2Co3 HCo- 3 H+ NaOH OH- Na+ H2O + Na H Co3 Bicarbonate/Carbonic acid buffer system
- 17. 17 Equilibrium shifts towardthe formation of acid Hydrogen ions that are lost (vomiting) causes carbonic acid to dissociate yielding replacement H+ and bicarbonate H+ HCO3 - H2CO3
- 18. Bicarbonate/Carbonic Acid Buffer System Plasma HCO3 is taken as measure of base excess or deficit. High concentration (24 mEq/L : 1.2 mEq/L) Alkali Reserve
- 19. Phosphate Buffer systemNa2 H PO4 / NaH2 PO4 When strong acid enter:- e.g. Hcl Na2HPo4 Na+ NaHPo- 4 HCl H+ Cl- Acid Phosphate (NaH2Po4) + NaCl NaH2Po4 NaHPo4 - H+ NaOH OH- Na+ Alkaline Phosphate (Na2HPo4) + H2O When an alkali enters:- :-NaOH Phosphate buffer system
- 20. Phosphate Buffer System NaHPO4 2++ H+ NaH2PO4 + NaH2PO4 + + OH- NaHPO4 2+ + H2O pK = 6.8 pK. Base : Acid concentration 4 : 1 Plasma – 5% of non-HCO3 buffer RBC -- 6% of non- HCO3 buffer in the form of 2,3 DPG Important in excretion of acids in urine
- 21. 21 1) Phosphate buffersystem Na2HPO4 + H+ NaH2PO4 + Na+ Most important in the intracellular system H+ Na2HPO4 + NaH2PO4 Click to animate Na+ +
- 22. 22 Na2HPO4 + H+NaH2PO4 + Na+ Alternately switches Na+ with H+ H+ Na2HPO4 + NaH2PO4 Click to animate Na+ + Disodium hydrogen phosphate
- 23. 23 Na2HPO4 + H+NaH2PO4 + Na+ Phosphates are more abundant within the cell and are rivaled as a buffer in the ICF by even more abundant protein Na2HPO4 Na2HPO4 Na2HPO4
- 24. 24 Regulates pH withinthe cells and the urine Phosphate concentrations are higher intracellularly and within the kidney tubules Too low of a concentration in extracellular fluid to have much importance as an ECF buffer system HPO4 -2
- 25. 25 PROTEIN BUFFER SYSTEM 2)Protein Buffer System Behaves as a buffer in both plasma and cells Hemoglobin is by far the most important protein buffer
- 26. 26 PROTEIN BUFFER SYSTEM Proteinsare excellent buffers because they contain both acid and base groups that can give up or take up H+ Proteins are extremely abundant in the cell The more limited number of proteins in the plasma reinforce the bicarbonate system in the ECF
- 27. 27 PROTEIN BUFFER SYSTEM AsH+Hb picks up O2 from the lungs the Hb which has a higher affinity for O2 releases H+ and picks up O2 Liberated H+ from H2O combines with HCO3 - HCO3 - H2CO3 CO2 (exhaled) Hb O2 O2 O2 H+
- 28. 28 PROTEIN BUFFER SYSTEM Venousblood is only slightly more acidic than arterial blood because of the tremendous buffering capacity of Hb Even in spite of the large volume of H+ generating CO2 carried in venous blood
- 29. Plasma Protein BufferSystem HPr H+ + Pr- • Mainly intracellular action • 95% of non-HCO3 buffer of plasma • Imidazole group of Histidine most important • 1 Albumin molecule contains 16 Histidines
- 30. 30 Pr - addedH+ + Pr - PROTEIN BUFFER SYSTEM Proteins can act as a buffer for both acids and bases Protein buffer system works instantaneously making it the most powerful in the body 75% of the body’s buffer capacity is controlled by protein Bicarbonate and phosphate buffer systems require several hours to be effective
- 31. 31 PROTEIN BUFFER SYSTEM Proteinsare very large, complex molecules in comparison to the size and complexities of acids or bases Proteins are surrounded by a multitude of negative charges on the outside and numerous positive charges in the crevices of the molecule - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + + + + + + + + + +
- 32. 32 PROTEIN BUFFER SYSTEM H+ions are attracted to and held from chemical interaction by the negative charges - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + + + + + + + + + + H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+ H+
- 33. 33 PROTEIN BUFFER SYSTEM OH-ions which are the basis of alkalosis are attracted by the positive charges in the crevices of the protein - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + + + + + + + + + + OH- OH- OH- OH- OH- OH- OH- OH- OH- OH- OH- OH-
- 34. Respiratory Regulation ofAcid-Base Balance Peripheral chemoreceptors – In carotids and aorta -- Stimulated by pH d/t CO2 accumulation or PO2 Central chemo-receptors -- In medulla oblongata -- Stimulated only by pH of CSF Onset of response – immediate Maximal response – 3-6 hrs
- 35.
- 36. 36 CHEMOSENSITIVE AREAS Chemosensitive areasof the respiratory center are able to detect blood concentration levels of CO2 and H+ Increases in CO2 and H+ stimulate the respiratory center The effect is to raise respiration rates But the effect diminishes in 1 - 2 minutes CO2 CO CO2 CO2 CO2 CO2 CO2 CO2 Click to increase CO2
- 37. 37 CHEMORECEPTORS Overall compensatory responseis: Hyperventilation in response to increased CO2 or H+ (low pH) Hypoventilation in response to decreased CO2 or H+ (high pH)
- 38. RENAL CONTROL OFpH pH of Plasma : 7.4 pH of Urine : 6.0 ... Kidney excretes acids
- 39. Renal regulation ofAcid-base Balance 1. Excretion of H+ (Na+ -H+ exchange) 2. Reclamation / Re-absorption of filtered HCO3 - 3. Renal production of NH3 and excretion of NH4 + ions 4. Excretion of H+ as H2PO4 - (titrable Acids) 5. Excretion of other acids
- 40. I Renal Regulationof pH of Blood Acidification of urine – pH 6.0 (1) Excretion of H+ and generation of HCO3 Plasma P. C. Tubular Cells Tubular Lumen Na HCO3 - Na+ Na HCO3 - + H+ H+ + Base- HB Excreted H2CO3 CO2 + H2O CA Urine pH is normally lower than blood pH
- 41. Na+ -H+ exchange •Renal tubular Na+ -H+ exchanger extrudes H+ into tubular fluid in exchange for Na+ • Exchange in acidosis and in alkalosis • Max urine acidity reached at pH 4.4
- 42. Na+ -H+ exchange CO2+H2O HHCO3 HCO3 - H+ Na+ HCO3 - Na+ H+ Na+ Na+HPO4 2- Na+H2PO4 - Tubular cell Plasma and interstitial fluid Glomerular filtrate
- 43. Na+ -H+ exchange •K+ compete with H+ in renal tubular NHE Renal intracellular K+ H+ excretion Acidity of body fluids • Hyperkalemia acidosis • Hypokalemia alkalosis • Potassium : weather vein : Serum K+ can be used as a poor man’s pH meter in the absence of pH measure.
- 44. (2) Reabsorption ofBicarbonate – (from Glomerular Filtrate) Plasma Tubular Cells Tubular Lumen (Glomerular filtrate) Na+ Na+ Na + HCO3 - HCO3 - + H+ H+ H2CO3 H2O + CO2 C.A . CO2 + H2O C.A . H2CO3 HCO3
- 45. Na+ HCO3 NH3 Na+ H+ Glutamin Glataminase Glutamic Acid NH3 Na+ NH4 HCO3 - + H+ H2CO3 CO2+ H2O C. A. (3) Excretion of Ammonium (NH4) Plasma Tubular Cells Tubular Lumen AA Oxidative Deamination
- 46. Renal production ofNH3 and excretion of NH4 + ions • NH3 gas diffuses from renal tubular cells into tubular lumen • In lumen, NH3 + H+ NH4+ • At the acid pH of urine NH4+ : NH3 10000:1 • NH4+ cannot cross cell membrane easily • Excreted with anions like PO4, Cl- or SO4
- 47. Renal production ofNH3 and excretion of NH4 + ions • In normal persons, NH4+ production in tubular lumen excretion of 60% of H+ associated with non-volatile acids (30-60 mmols/day) • In acidosis, greatest net renal excretion of H+ as NH4+ • Max. rate of NH3 production (400 mmols/d) by 3 days • In CRF, insufficient NH3 production leads to acidosis
- 48. Plasma Tubular Cells TubularLumen Na+ Na+ Na HPO4 - HCO3 - + H+ H+ H2CO3 CO2 + H2O C.A . Excreted NaH2 PO4 HCO3 6.0 7.4 Na2 HPO4 Na+ (4) Excretion of Titrable Acid
- 49. H+ + Na+Na+HPO4 2- Na+ + Na+H2PO4 - • H+ secreted by NHE into tubular lumen • Depends on PO4 filtered by glomeruli and pH of urine 30 mmols/d of H+ excreted as H2PO4 90% of titratable acidity of urine • pH gradient maintained, Na+ conserved Excretion of H+ as H2PO4 -
- 50. Excretion of H+as H2PO4 - • High protein intake PO4 production and filtration • Acidemia PO4 excretion buffer for reaction with H+ GFR as in renal disease H2PO4 excretion Urine pH is normally lower than blood pH
- 51. 5. Excretion ofother acids • Strong acids. fully ionized at urinary pH • H+ buffered by a base and equal no. of cations like Na+, K+ or NH4+ lost along with the anions of these acids • Some acids remain undissociated at acid pH eg. Acetoacetic acid , -OH Butyric acid • They are excreted partially in non-dissociated form
- 52. Regulation of Acid– base balance (E. C. F.) (1) Plasma Buffer System - Bicarbonate Buffer is used up ( HCO3 -) 1st line of defence 2nd line of defence (2) Respiratory compensation 3rd line of defence tends to restore Blood pH - Re-absorption of HCO3 - Excretion of H+ Cellular Buffers – 50 – 60% of B. capacity (A) (B) Bone Skeletal muscles H+ enters the cell en exchange of Na+ & K+ to prevent severe acidosis by hyperventilation ( H2CO3) (3) Renal mechanism
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- 55. Acid-Base Disorders Primary Change Compensatory response Metabolic AcidosisHCO3 PCO2 Alkalosis HCO3 PCO2 Respiratory Acidosis Acute PCO2 HCO3 Chronic PCO2 HCO3 Alkalosis Acute PCO2 HCO3 Chronic PCO2 HCO3
- 59. Metabolic Acidosis Anion Gap: Due to unmeasured anions eg. Proteins, SO4 2-, HPO4 2- • Unmeasured cations: calcium, magnesium, gamma globulins, potassium. • Unmeasured anions: albumin, phosphate, sulfate, lactate. Anion Gap = ( Na+ + K+) – (Cl- + HCO3 -) (142 + 4) – (106 + 24) = 16 mEq/L
- 60. Anion Gap • Highanion gap acidosis (Organic acidosis) : HCO3 consumed in buffering excess H+ • Normal anion gap acidosis (Inorganic acidosis) : Loss of HCO3-rich fluid from Kidney or GIT
- 61. Decreased anion gap •Decrease in unmeasured anions – Hypoalbuminemia • Increase in unmeasured cations – Hypercalcemia – Hypermagnesemia – Hyperkalemia – Multiple myeloma – Lithium toxicity
- 62. High AG Acidosis Methanoltoxicity Formate Uremia of renal failure, Ketoacidoses Sulfuric, phosphoric, organic Diabetes mellitus,Ethyl alcohol toxicity,starvation Acetoacetate, -OH Butyrate Paraldehyde toxicity INH/Iron toxicity,ischemia Organic mainly lactate Lactic acidosis Lactate Ethylene glycol toxicity Hippurate, Glycolate, oxalate Salicylate toxicity Salicylate, organic
- 63. Normal Gap Acidosis •H: hyperalimentation • A: acetazolamide • R: RTA • D: diarrhea • U: rectosigmoidostomy • P: pancreatic fistula
- 64. Compensatory mechanisms in MetabolicAcidosis • HCO3 / PCO2 < 20/1 • Respiratory mechanism: pH Hyperventilation PCO2 • Renal mechanism: Excretion of H+ (as much as 500 mmol/d) HCO3 (Chemically fully compensated metabolic acidosis)
- 65. Respiratory Acidosis Causes: Elimination of CO2 Types: • Acute • Chronic Conditions: • Factors directly depressing Respiratory Centre • Conditions affecting the respiratory apparatus • Others
- 66. Respiratory Acidosis • CO2above normal with drop in extracellular pH. • Disorder of ventilation. • Rate of CO2 elimination << than production • 5 main categories: – CNS depression – Pleural disease – Lung diseases such as COPD and ARDS – Musculoskeletal disorders – Compensatory mechanism for metabolic alkalosis
- 67. Respiratory Acidosis -Compensatory Mechanisms • Acute state: • Buffer system – Excess carbonic acid buffered by non HCO3 - buffers like Hb and protein buffer systems. Kidney involvement minimum at this stage. HCO3 - appears like metabolic alkalosis – 10 mm Hg increase in CO2 / pH should decrease by .08 • Respiratory mechanism – When primary defect not in Respiratory centre PCO2 respiratory centre stimulation rate and depth of respiration pH approaches normal
- 68. Respiratory Acidosis -Compensatory Mechanisms • Chronic: • Renal mechanism – not effective before 6-12 hrs, not optimal till 2-3 days Chronic cases almost complete compensation • Mechanism : Renal synthesis and retention of HCO3 -. • As HCO3 - added to blood, Cl- will decrease to balance charges. – This is the hypochloremia of chronic metabolic acidosis. – 10 mm Hg increase in CO2 / pH should decrease by .03
- 71. Nonpulmonary Stimulation ofRespiratory Centre • Anxiety, Hysteria • Febrile states • Gram-negative septicemia • Metabolic encephalopathy • CNS infections • CVAs • Intracranial surgery • Hypoxia – High altitude, severe anemia • Drugs – Salicylates, catecholamines, Progesterone • Pregnancy • Hyperthyroidism
- 72. Pulmonary Disorders andOthers • Pneumonia • Asthma • Pulmonary emboli • Interstitial lung disease • Large right to left shunt • Congestive heart failure • Respiratory compensation after correction of metabolic acidosis • Others – Ventilator induced hyperventilation
- 73. Respiratory Alkalosis • Twostages of compensation First stage: RBC & Tissue buffers provide H+ ions that consume some amount of HCO3 - Second stage operational in prolonged akalosis. Dependant on decreased renal reclamation of HCO3 - as in metabolic alkalosis.
- 75. Exogenous Base • Iatrogenic --HCO3 containing IV fluid therapy -- Massive blood transfusion(Na citrate overload) -- Antacids and cation-exchange resins in dialysis pts.
- 76. Compensatory Mechanisms • Respiratory: pH Depressed respiratory centre Retention of CO2 (hypercapnia) HCO3 - / PCO2 approaches normal although actual levels of both remain high (PCO2 increases 6 mm Hg for each 10 mmol/L rise in HCO3) • Renal : Na-H exchange, NH3 formation, reclamation of HCO3 - Above Responses blunted by hypokalemia and hypovolemia
- 77. It’s not magicunderstanding ABG’s, it just takes a little practice!
- 78.
- 79. CASE STUDY 1 APatient was brought to the emergency in a confused and semi-conscious state. There was laboured breathing and the respiratory rate was 34/min. Expired air had a sweet Acetone like smell. On examination the following were the findings: Parameters Serum Values in the Pt. Reference Values Blood Sugar 340 mg/dl 80 – 120 mg/dl HCO3 - 15 mmol/L 22 – 26 mmol/L H2 co3 1.2 mmol/L 1.2 mmol/L pH 7.3 7.35 – 7.45
- 80. CASE STUDY 2 Anobese Patient was brought to the emergency with c/o dizziness and confusional state. There was h/o COPD. On examination the following were the findings: Parameters Serum Values in the Pt. Reference Values Blood Sugar 110 mg/dl 80 – 120 mg/dl HCO3 - 24 mmol/L 22 – 26 mmol/L H2 co3 2.4 mmol/L 1.2 mmol/L pH 7.5 7.35 – 7.45
- 81. Physiology and Disordersof Acid-Base Metabolism S.L.O : Define Acids, Bases, pH & Buffers Name the different buffer systems in the body Action of each buffer system Role of Lungs. Role of Kidneys Anion Gap Blood Values of certain parameters Clinical abnormalities of pH
- 84. • 55 yearold male patient admitted in hospital with shortness of breath. He is taking Diuretics for Hypertension and 75mg aspirin daily. Positive history of cigarettes smoking. • PH= 7.53 • PaCO2= 37 mmHg • PaO2= 62mmHg • SaO2=87% • HCO3= 30