Acid-base Balance and its Disorders

1. Acid-base Balance and its Disorders Prof. Dr. Meltem Pekpak

2. For optimal functioning of cells.. • Acids and bases in the body must be in balance. • We all consume every day food and drinks which contain acids, metabolism produces also acids...

3. Body pH Balance • Chemical blood buffers: • Lungs, • Cells, • Kidneys • Defences against changes in hydrogen concentration (getting acidotic..)

4. You get acidotic every day ! • While living, eating and drinking...there is.. • Production of 1 mmol of fixed acid/kg body weight per day (60 kg=60 mmol/day)

5. Buffers • Extracellular: • Hemoglobin • (‘Chloride shift’-for each chloride leaving the cell-one bicarbonate ion enters) • Plasma protein • (with the liver, varying the amount of H-ions in the protein structure) • Bicarbonate system: • Normal acid to base ratio is 20:1 • 20 parts bicarbonate to 1 part carbonic acid (H2CO3=CO2), • Neutralizing a strong acid bicarb. will be lost

6. Human Acid-baseHomeostasis • Tight regulation: • CO2 tension • by respiratory excretion (of volatile acids) • Plasma bicarbonate [HCO3-] • By renal HCO3- reabsorption and • Elimination of protons produced by metabolism • pH is determined by CO2 tension and [HCO3-]

7. Physiology of Buffering: • Ability of a solution containing a weak or poorly dissociated acid and its anion (a base) to resist change in pH when strong acid or alkali is added • 1 ml of 0.1 M HCl to 9 ml distilled water = • [H+]from 10 -7 M to 10 -2 M= pH from 7 to 2 • 1 ml of 0.1 M HCl to 9 ml of phosphate buffer: dissoc. H+combines with [HPO42-] = (H2PO4-) • pH fall of only 0.1= to 6.9

8. Bicarbonate Buffer • Extracellular most important buffer • Proteins and phosphate buffer less important • Intracellularphosphate- most important b. • Equilibrium conditions because abundant carbonic anhydrase in blood • H+ + HCO3- H2CO3  H2O + CO2 • [H+ ]= Keq x [H2CO3 ]/[HCO3-]

9. Equations • H+ + HCO3- H2CO3  H2O + CO2 • Equilibrium • [H+ ]= Keq x [H2CO3 ]/[HCO3-]

10. Total Acid- base Metabolism Henderson-Hasselbalch 1909,1916 Altered by Buffering Primarily Altered in Metabolic Disorders HCO3- • pH = pK + log ------------ PaCO2 Metabolic comp. Respiratory component Primary Respiratory Disorders Altered by Respiratory Compensation for Metabolic Disorders Result of Metabolic and Respiratory Interplay

11. Normal Values • [HCO3-] ~ 24 mM • PaCO2 = 38 torr • pH ~ 7.42 • Plasma HCO3- regulation by • reclaiming filtered HCO3- and • generating new HCO3- (carboanhydrase) • ( to replace the lost internally titrating metabolic acid and externally from the GI tract) • Production of 1 mmol of acid/kg body weight per day (60 kg=60 mmol/day)

12. Renal Acid -base Handling • Two seperate functions: • Bicarbonate reabsorption • Net acid secretion

13. Proximal Tubular BicarbonateReclamation Process (90 %) Two vehicles for apical H+ secretion (Na+/H+ exchanger), H+ATPase. Basolateral ion pumps: Na+/K+ ATPase, (Na+HCO3-)symporter,HCO3-/Cl- Exchanger. The role of carbonic anhydrase (CA) in tubular cell and brush border

14. Net Acid Excretion • Urine is acid = pH~ 4.5 • Buffer salts are in the tubular fluid • Phosphate is the most important buffer in urine: HPO42- + H+ = H2PO4- • Nonvolatile (fixed) acids (anions= sulfates, phosphates) must be accompanied in the urine by equivalent cations (Na +, K +, Ca + +) for maintenance of electrical neutrality • In acid urine ammonium helps to keep [H+ ] (ammonia NH3+ to NH4+)

15. Clinical Evaluation • Patient history • Clinical presentation • Acidemia Hyperventilation • Alkalemia Paresthesias and Tetany • Laboratory: Blood acid-base status: • Blood pH (4 º C, with anticoagulant, promptly), • Urine pH • Plasma and urine electrolyte concentration • Lactate concentration

16. Acidosis • Clinical effects of severe acidosis: pH <7.2 • Cardiovascular system effects: • Decreased myocardial contractility • Decreased cardiac output • Cardiac failure • Hypotension • Decreased hepatic and renal blood flow • Centralization of effective blood volume • Tissue hypoxia • Pulmonary edema

17. Metabolic acidosis • Hallmark is [HCO3-] • 1. Acid production  net acid intake  above net renal excretion (ketoacidosis, lactic acidosis, ammonium chloride loading) • 2. failure of renal net excretion (chronic renal failure, renal tubular acidosis) • 3. Bicarbonate loss via the gastroinestinal tract (diarrhea, gastrointestinal fistula) • 4. Nonbicarbonate solutions added to ECF (dilutional acidosis)

18. Steps of evaluation • 1.Examine pH= Reduction ( 7.2)  Acidosis • Increase (7.5) Alkalosis • 2. Examine directional change of PCO2 • and [HCO3-] , • pH acid, HCO3- low  Metabolic acidosis • pH alkal., HCO3- high  Metabolic alkalosis • 3. Assess degree of compensation: Mixed acid-base disorder? • Metabolic acidosis  PCO2  • Metabolic alkalosis  PCO2 • Failure of respiratory compenstion= primary respiratory acid-base disorder • Never to initial pH through compensation !!

19. Steps of evaluation • 4. Calculate the serum anion gap • Is the acid-base disorder organic or mineral in origin?? • We use venous sample blood electrolytes: • Electroneutrality demands: • Serum anion gap, that means: • [Na+] + [UC]= [Cl-] +[Total CO2] + [UA] • (U means: unmeasured)

20. Normally the serum anion gap is about 9 (6-12 mEq/l), a major increase in Anion gap > 26 mEq/l always implies existence of an organic acidosis

21. Differential Diagnosis of Metabolic Acidosis • Normal anion gap Increased anion gap • (hyperchloemic) (organic)_________ • GI loss ofHCO3- acid production • Diarrhea Lactic acidosis • Renal tub. Acidosis Diab. Ketoacidosis • Parenteral alimentation Toxic alcohol,salicy. • Carbonic anhydr. İnh. Acute renal failure • K-sparing diuretics Chronic renal failure

22. Increased anion gap Metabolic acidosis • Ketoacidosis (diabetic) • Uremia (renal failure) • Salicylate intoxication • Starvation • Methanol intoxication • Alcohol ketoacidosis • Unmeasured osmoles (intoxication) • Lactic acidosis

23. Simple decompensatedAcid-base Disorders • Acid Base Dis.: pH pCO2 HCO3- • Metabolic acidosis    • Respiratory acidosis    • Metabolic alkalosis    • Respiratory alkalosis   

24. Compensatory Response one half of acid load is buffered by nonbicarbonate buffers= Bone, protein, red cells.. • PCO2  (Kussmaul) • compensatory response after 15-30 minutes, • 5 days up to maximal • Kidney: • Metabolic acidosis •  processing of glutamine into NH4+ (ammonia to ammonium for better H-excretion) and • Bicarbonate generation (and reclaiming)

26. Respiratory Acidosis • Acute increase in pCO2 • Buffered primarily by intracellular buffers • Chronic state: • Kidneys compensation: • Increase net acid excretion, • (48 hours for fully development) • Underlying cause: • Central nervous system disease, • lung (COPD)and heart disease, • sedatives and opiates depressing the respiratory center • Hypercapnic encephalopathy can develop

27. Metabolic Alkalosis • Plasma bicarbonate [HCO3-]  = pH  • 1) H+ GI loss or shift into cells • 2) Excess HCO3- Administration of  bicarbonate, or precursors:  lactate, acetate, citrate or Failure to excrete: mineralocorticoid effect • 3) Loss of fluid with Diuretic therapy [Cl-], [K+] and [H+] loss from plasma- extracellular volume contraction

28. Alkalosis

29. Volume Depletion and Metabolic Alkalosis • Absolute volume depletion: • Loss of salt by bleeding or vomitting or • Effective volume depletion: • Heart failure, cirrhosis, nephrotic syndrome  whenever •   GFR •  Tubular HCO3- reabsorption • Because proximal tubule reabsorption is enhanced for Na and water

30. Compensatory Respiratory Response • Alveolar hypoventilation(hypercapnia) • (limited pCO2riseto 50-60 mm Hg) • Kidneys: • Excretion of HCO3-proportional to GFR (excessive)

31. Respiratory Alkalosis pCO2 , pH  due to: Hypoxia (compensatory hyperventilation) • Acute: pulmonary edema or emboli, pneumonia, • Chronic: severe anemia, high altitude, hypotension Respiratory center stimulation • Pregnancy, Anxiety, Fever, heat stroke, sepsis, salisylate intox., cerebral disease, hepatic cirrhosis, Increased mechanical ventilation

32. Respiratory Alkalosis • Most common acid-base disorder • Physiologic in pregnancy and high altitude • Bad prognosisin critically ill patients (the higher hypocapnia, the higher mortality) • Hyperventilation, • Perioral and extremity paresthesias, • Light-headedness, • Muscle cramps, • Hyperreflexia, seizures,  ionized Ca  tetany

33. Metabolic Alkalosiswith and without Volume Depletion • Volume depleted- Chloride responsive metabolic acidosis: • Urine chloride is low (<10 mmol/l) • Due to: • Gastric fluid losses • Stool losses • Diuretic therapy

34. Metabolic AlkalosisExcessive Mineralocorticoids • Mineralocorticoidsstimulatehydrogenionsecretion • And thisbicarbonate reabsorption • Urinary chloride is normal (<20 mmol/l) • Hypokalemia • Primary aldosteronizm, • Bartter’s Syndrome, • Cushing Syndrome • Renovascular hypertension

36. Proximal Tubular Bicarbonate Reclamation Process (90 %) The proximal tubulus cells form carbonic acid from carbon dioxide and water under the influence of the enzyme carboanhydrase (CA). Carbonic acid ionizes to yield hydrogen and bicarbonate . Hydrogen formed in the cell exchanges with sodium in the tubular fluid (dashed circle). As a net effect Sodium bicarbonate is reabsorbed, and the hydrogen ion secreted into the tubular lumen is buffered by filtered bicarbonate.

37. Henderson-Hasselbach 1909,1916 • H2CO3 = p CO2 +solubility in physiol. Fluids • [H+ ]= K x [S x pCO2 ]/[HCO3-] Antilog of both sides: pH= pK + log10 [HCO3-] / [S x PCO2] In blood at 37º C, pK =6.1 and S is 0.03 pH= 6.1+ log10 [HCO3-] / [0.03 x PaCO2]