1. Aproach to the patient with acid-base disorders
Zehra Eren,M.D.

2. LEARNING OBJECTIVES recall normal acid-base balance
recall buffer systems in regulation of pH
recall Henderson-Hasselbach Equation
describe metabolic acidosis and alkalosis
describe respiratory acidosis and alkalosis
manage acid-base disorders

3. LEARNING OBJECTIVES H.L. MENCKEN
"Life is a struggle, not against sin, not against the Money Power, not against malicious animal magnetism, but against hydrogen ions."
H.L. MENCKEN

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

5. Buffer Systems in Regulation of pH
Extracellular fluid:
- bicarbonate ion (HCO3-) /carbonic acid
H++HCO3- ⇔ H2CO H2O + CO2
- plasma proteins
- phosphate ions
- Ca2+ and HCO3- release of bone
carbonic
anhydrase

6. Buffer Systems in Regulation of pH
İntracellular fluid
- hemoglobin
- cellular proteins
- organophosphate complexes
- HCO3- by the H+/ HCO3- transport mechanism

7. Henderson-Hasselbach Equation
pH=6.1+log pH
[H+]nmol/L
[HCO3- ] (mEq/L)
0.03XpCO2 (mm Hg)

8. Normal Levels
pH:
pCO2: mmHg
HCO3- : mEq/L

9. pH Acidosis <7.35-7.45> Alkalosis HCO3- ↑↓ → Metabolic
CO2 ↑↓ → Respiratory

10. Compensatory response to acid-base disorders
Metabolic Acidosis/Alkalosis→
reducing / increasing CO2
Respiratory Acidosis/Alkalosis→
renal secretion / reabsorption of HCO3-/H+

12. Metabolic Acidosis
Fall in HCO3- concentration with fall in pH
Compensatory response:
fall in pH causes increased respiration, reducing CO2
1.2 mmHg fall in arterial PCO2 for every 1 meq/L reduction in the serum HCO3 concentration

13. Formulas Arterial PCO2 = 1.5 x serum HCO3 + 8 ± 2 (Winters’ equation)
Arterial PCO2 = Serum HCO3 + 15
Arterial PCO2 should be similar to the decimal digits of the arterial pH (eg, 25 mmHg when the arterial pH is 7.25, a setting in which the serum HCO3 concentration would be approximately 11 meq/L)

14. Causes of Metabolic Acidosis
İncreases acid load (H+)
HCO3- loses
- extrarenal: gastrointestinal
- renal

16. Plasma Anion Gap
[Na+] - ([Cl-]+[HCO3- ])
9 ± 3 mEq/L (mmol/L)

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

18. Anion Gap Anions Cations Cl+HCO3 Na Albumin Phosphates K Sulfates Ca
Lactates Mg
Urates

19. 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

20. 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

23. Urinary Anion Gap UAG=( UNa + UK) – UCl (-20) — (-50) mEq/L (NH4 +)
The urinary anion gap reflects the ability of the kidney to excrete NH4Cl

24. Symptoms and Signs mainly those of the underlying disorder
compensatory hyperventilation is an important clinical sign
Kussmaul breathing (deep, regular, sighing respirations) may be seen with severe metabolic acidosis

25. Laboratory Findings Blood pH, serum HCO3-, and PCO2 are decreased
Anion gap may be normal (hyperchloremic) or increased (normochloremic)
Hyperkalemia may be seen

26. Treatment: Normal Anion Gap Acidosis
Treatment of RTA is mainly achieved by administration of alkali (either as bicarbonate or citrate) to correct metabolic abnormalities and prevent nephrocalcinosis and CKD
Proximal RTA:
-large amounts of oral alkali (10–15 mEq/kg/d)
-thiazides may reduce the amount of alkali required
-mixture of sodium and potassium salts is preferred
Distal RTA:
- requires less alkali(1–3 mEq/kg/d)

27. Treatment: Normal Anion Gap Acidosis
Type IV RTA:
-dietary potassium restriction may be necessary and potassium-retaining drugs should be withdrawn
-Fludrocortisone may be effective in cases with hypoaldosteronism, but should be used with care, preferably in combination with loop diuretics.

28. Treatment: Increased Anion Gap Acidosis
Treatment is aimed at the underlying disorder, such as insulin and fluid therapy for diabetes and appropriate volume resuscitation to restore tissue perfusion
Supplemental HCO3– is indicated for treatment of hyperkalemia
Large amounts of HCO3– may have deleterious effects, including hypernatremia, hyperosmolality, volume overload, and worsening of intracellular acidosis

29. Treatment: Increased Anion Gap Acidosis
In salicylate intoxication:
-alkali therapy must be started to decrease central nervous system damage unless blood pH is already alkalinized by respiratory alkalosis, since an increased pH converts salicylate to more impermeable salicylic acid
In alcoholic ketoacidosis:
- thiamines should be given with glucose to avoid Wernicke encephalopathy
The bicarbonate deficit can be calculated as follows:
HCO3=0.5 x b.w. (kg) x (24-HCO3)

30. Metabolic Alkalosis Rise in HCO3- concentration with rise in pH
Compensatory response:
rise in pH causes decreased respiration, increasing CO2
raise the PCO2 by 0.7 mmHg for every 1 meq/L elevation in the serum HCO3 concentration

31. Causes of Metabolic Alkalosis
Loss of Hydrogen
1.Gastroinrestial losses:
-gastrik section
-vomiting
-antacid therapy
-chloride-losing diarrhea
2.Renal losses:
-diuretics
-mineralocorticoid excess
-hypercalcemia/milk-alkali syndrom
-low chloride intake
3. H+ shift into cell
-hypokalemia

32. Causes of Metabolic Alkalosis 2
Retention of Bicarbonate
-massive blood transfusions
-NaHCO3 administration
Contraction alkalosis
-diuretics
-sweat losses in cystic fibrosis

35. Symptoms and Signs There are no characteristic symptoms or signs
Orthostatic hypotension may be encountered
Concomitant hypokalemia may cause weakness and hyporeflexia
Tetany and neuromuscular irritability occur rarely

36. Laboratory Findings The arterial blood pH and bicarbonate are elevated
Serum potassium and chloride are decreased
The urine chloride can differentiate between saline-responsive (< 25 mEq/L) and unresponsive (> 40 mEq/L) causes

37. Treatment Saline-Responsive Metabolic Alkalosis
-correction of the extracellular volume deficit with isotonic saline
-H2-blockers or proton pump inhibitors may be helpful in patients with alkalosis from nasogastric suctioning
-acetazolamide will increase renal bicarbonate excretion
Saline-Unresponsive Metabolic Alkalosis
-surgical removal of a mineralocorticoid-producing tumor -blockage of aldosterone effect with an ACE inhibitor or with spironolactone

38. Respiratory Acidosis Rise in CO- concentration with fall in pH
Compensatory response:
fall in pH causes increased renal H+ secretion, raising HCO3- concentration
serum HCO3 concentration increase by about 1 meq/L for every 10 mmHg elevation in the PCO2

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

40. 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 sclerosis
2.Kyphoscoliosis

41. 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

42. Treatment Ventilatory support
NaHCO3− therapy controversial in this disorder:
-Perhaps beneficial in severely acidemic patient (eg, status asthmaticus) versus
-Hazards of therapy in patients with reversible hypercapnea (eg, chronic obstructive pulmonary disease in which respiratory drive is depressed)

45. Respiratory Alkalosis
Fall in CO- concentration with rise in pH
Compensatory response:
rise in pH causes diminished renal H+ secretion, lowering HCO3- concentration
serum HCO3 concentration fall 2 meq/L for every 10 mmHg decline in the PCO2

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

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

48. Treatment Correction of underlying disorder
Increasing Pco2 in inspired air (breathing into paper bag) in setting of acute respiratory alkalosis

49. Diagnosis of acid-base disorders: a stepwise approach
Step1: Obtain arterial blood gas and electrolyte values simultaneously
Step2: Define the acid-base disorders
Step3: Calculate the anion gap
Step4:Define the limits of compensation to distinguish simple from mixed acid-base disorders
Step5:Make the diagnosis

51. Case pH:7.23 pCO2: 40 mmHg HCO3: 18 mEq/L Na: 143 mEq/L K: 3.7 mEq/L
Cl: 115 mEq/L

52. pH:7. 23 pCO2:40mmHg HCO3: 18mEq/L Na:143mEq/L, K:3
pH:7.23 pCO2:40mmHg HCO3: 18mEq/L Na:143mEq/L, K:3.7mEq/L,Cl:115mEq/L Anion gap=143-(18+115)= 10mEq/L
Acidosis
Normal
Metabolic
Normal

53. Major reactions involved in ammonia production in the kidneys
Ganong's Review of Medical Physiology, 24e, 2012

54. Principal Buffers in Body Fluids