1. Acid-Base Balance Zehra Eren,M.D.

2. LEARNİNG OBJECTİVES explain normal acid-base balance explain buffers systems in regulation of pH explain compensatory response to acid-base disorders recognize metabolic acidosis recognize metabolic alkalosis recognize respiratory acidosis and alkalosis

3. Normal Acid-Base Balance Daily net acid production: 1mEq hydrogen ions(H + ) per kilogram H + : 0.0004 mEq/L (40nmol/L)= pH: 7.40 Arterial pH:7.35-7.45 İntracellular pH:7.0-7.3

4. Buffer Systems in Regulation of pH Extracellular fluid: - bicarbonate ion (HCO 3 - ) /carbonic acid H + +HCO 3 - ⇔ H 2 CO 3 H 2 O + CO 2 - plasma proteins - phosphate ions - Ca 2+ and HCO 3 - release of bone carbonic anhydrase

5. Buffer Systems in Regulation of pH İntracellular fluid - hemoglobin - cellular proteins - organophosphate complexes - HCO 3 - by the H + / HCO 3 - transport mechanism

6. Henderson-Hasselbach Equation pH=6.1+log pH7.00 7.40 7.70 [H + ] n mol/L 100 40 20 [HCO3- ] (mEq/L) 0.03XpCO 2 (mm Hg)

7. Normal Levels pH: 7.35-7.45 pCO 2 : 37-45 mmHg HCO 3 - : 22-26 mEq/L

8. pH Acidosis Alkalosis HCO 3 - ↑↓ → Metabolic CO 2 ↑↓ → Respiratory

9. Compensatory response to acid-base disorders Metabolic Acidosis/Alkalosis → reducing / increasing CO 2 Respiratory Acidosis/Alkalosis → renal secretion / reabsorption of HCO 3 - /H +

10. Metabolic Acidosis Fall in HCO 3 - concentration witt fall in pH Compensatory response: fall in pH causes inreased respiration, reducing CO 2 1.2 mmHg fall in arterial PCO2 for every 1 meq/L reduction in the serum HCO3 concentration

11. Causes of Metabolic Acidosis İncreases acid load (H + ) HCO 3 - loses - extrarenal: gastrointestinal - renal Decreased renal acid excretion

14. Serum Anion Gap [Na + ] - ( [Cl - ]+[HCO 3 - ] ) 9 ± 3 mEq/L (mmol/L)

15. Serum Anion Gap Serum AG= Measured cations – Measured anions Serum AG= Na - (Cl+HCO3) Serum AG= Unmeasured anions – Unmeasured cations

17. HIGH SERUM ANION GAP increase in unmeasured anions metabolic acidosis, hyperalbuminemia, hyperphosphatemia, or overproduction of an anionic paraprotein reduction in unmeasured cations hypokalemia, hypocalcemia, hypomagnesemia

18. LOW SERUM ANION GAP Decrease in unmeasured anions primarily due to hypoalbuminemia Increase in unmeasured cations hyperkalemia, hypercalcemia, hypermagnesemia, or severe litium intoxication Bromide ingestion serum protein electrophoresis should be obtained to look for a cationic paraprotein that is present in some patients with multiple myeloma

20. Urinary Anion Gap UAG=( UNa + UK) – UCl (-20) — (-50) mEq/L (NH 4 +)

25. Metabolic Alkalosis Rise in HCO 3 - concentration with rise in pH Compensatory response: rise in pH causes decreased respiration, increasing CO 2 raise the PCO2 by 0.7 mmHg for every 1 meq/L elevation in the serum HCO3 concentration

28. GASTROINTESTINAL HYDROGEN LOSS Each meq of hydrogen lost generates one meq of bicarbonate: the hydrogen ion is derived from water, while the associated hydroxyl ion combines with carbon dioxide to form bicarbonate

29. Development and maintenance of metabolic alkalosis An elevation in the plasma bicarbonate concentration due to hydrogen loss in the urine or gastrointestinal tract, hydrogen movement into the cells, the administration of bicarbonate, or volume contraction around a relatively constant amount of extracellular bicarbonate (called a contraction alkalosis) A decrease in net renal bicarbonate excretion (due both to enhanced reabsorption and reduced secretion), since rapid excretion of the excess bicarbonate would normally correct the alkalosis

30. Factors responsible for the rise in net bicarbonate reabsorption Effective circulating volume depletion, including reduced tissue perfusion in edematous states such as congestive heart failure and cirrhosis Chloride depletion and hypochloremia Hypokalemia

31. EFFECTIVE VOLUME DEPLETION Aldosterone directly enhances acidification by increasing the activity of the H-ATPase pumps in the luminal membrane of the intercalated cells. This pump promotes the secretion of hydrogen ions into the tubular lumen, thereby increasing the reabsorption of bicarbonate. Aldosterone-stimulated sodium reabsorption in the adjacent principal cells makes the lumen electronegative due to the loss of cationic sodium. This potential minimizes the passive back-diffusion of hydrogen ions out of the lumen, allowing the urine to become much more acid than the plasma. Decreased chloride delivery diminishes bicarbonate secretion in the type B intercalated cells, which is thought to be an important component of the normal renal response to a bicarbonate load.

32. CHLORIDE DEPLETION Vomiting Diuretic therapy ->hydrogen and chloride loss The hypochloremia can contribute to the reduction in bicarbonate excretion by increasing distal reabsorption and reducing distal secretion; this effect of chloride may be more important than the associated volume depletion

33. HYPOKALEMIA Hypokalemia directly increases bicarbonate reabsorption

39. Respiratory Acidosis Rise in CO - concentration with fall in pH Compensatory response: fall in pH causes increased renal H+ secretion, raising HCO 3 - concentration

41. Causes of Respiratory Acidosis İnhibition of respiratory drive -opiates -anesthetics -sedatives -central sleep apnea -obesity -central nervous system lesions

42. Causes of Respiratory Acidosis 2 Disorders of respiratory muscles 1.Muscle weakness; -myastenia gaves -periodic paralysis -aminoglycosides -Guillan-Barre syndrom -spinal cord injury -acute lateral sclerosis -multiple sclersis 2.Kyphoscoliosis

43. Causes of Respiratory Acidosis 3 Upper airway obstruction -obstructive sleep apnea -laryngospasm -aspiration Lung diseases -pneumonia -severe asthma -pneumothorax -acute respiratory disress syndrom -chronic obsructive pulnmonery disease -interstitial lung disease

44. Respiratory Alkalosis Fall in CO - concentration with rise in pH Compensatory response: rise in pH causes diminished renal H + secretion, lowering HCO 3 - concentration

45. Causes of Respiratory Alkalosi s Hypoxemia 1.Pulmonary disease -pneumonia -interstitial fibrosis -emboli -edema 2.Congestive heart failure 3.Anemia

46. Causes of Respiratory Alkalosis 2 Stimulation of the medullary respiratory center -hyperventilation -hepatic failure -septicemia -salycilate intoxication -pregnancy -neurologic disordrs Mechanical ventilation

48. Suggested Reading Goldman's Cecile Medicine, Goldman L, Schafer AI Case files Internal Medicine, Toy Patlan Current Medical Diagnosis and Treatment, Maxine A. Papadakis, Stephen J. McPhee, Eds. Michael W. Rabow, Associate Ed. Current Diagnosis & Treatment: Nephrology & Hypertension Edgar V. Lerma, Jeffrey S. Berns, Allen R. Nissenson