1. Acidosis Dr. Elmukhtar Habas PhD Fachärzt Internal Medicine Fachärzt Nephrology Dr. med.

2. Normal ABG PaCO2 4.8-6.1 kPa(35-45 mmHg) PaO2 10-13.3 kPa(75-100 mmHg) pH7.35-7.45[H+] 35-45 mol/L Bicarbonate 22-26 mmol/L BE Base Excess-2 to +2

4. Acid-Base disturbance disturbancePHPco2HCO3 Metabolic Acidosis Low Respiratory Acidosis LowHigh Metabolic Alkalosis High Respiratory Alkalosis HighLow Normal ABG7,36-7,4435-45mmHg22-26 mmol/l

5. LOW EC pH HIGH NORMAL No disturbance Or Mixed disturbance Mixed if PCO2+HCO3 both low or both high or plasma anion gap wide Alkalemia Acidemia Low PCO2 Respiratory Alkalosis High HCO3 Metabolic Alkalosis Low HCO3 High PCO2 Metabolic Acidosis Respiratory Acidosis

6. Definition of Acidosis Is a process that tends to lower the extracellular fluid pH (which is equivalent to raising the hydrogen concentration) that can be either by A) a fall in the ECF (or plasma ) bicarbonate concentration. b) an elevation in the PCO2 in ECF.

7. Types of Acidosis Metabolic acidosis. -Low bicarbonate, low PH, normal PCO2. -Usually associated with hyperK. Respiratory acidosis: -Low PH, high PCO2 &Normal or high Hco3 -can be hyperk+

8.  Each day approximately 15,000 mmol of carbon dioxide (which can generate carbonic acid as it combines with water) and 50 to 100 meq of nonvolatile acid (mostly sulfuric acid derived from the metabolism of sulfur-containing amino acids) are produced.  Acid-base balance is maintained by normal pulmonary and renal excretion of carbon dioxide and acid, respectively.  Renal excretion of acid involves the combination of hydrogen ions with urinary titratable acids, particularly phosphate (HPO42- + H+ —> H2PO4-) or with ammonia to form ammonium.  since ammonia production from the metabolism of glutamine can be appropriately increased in the presence of an acid load.

9. Henderson-Hasselbalch equation:  pH = 6.10 + log ([HCO3-] ÷ [0.03 x PCO2]) -pH is equal to (-log [H+]) -6.10 is the pKa (equal to -log Ka). -Ka is the dissociation constant for the reaction -0.03 is equal to the solubility constant for CO2 in the extracellular fluid. -PCO2 is equal to the partial pressure of carbon dioxide in the extracellular fluid.

10. Metabolic acidosis Low Hco 3 -, low Ph Metabolic acidosis diagnostic chart AG= Na+ - (Cl- +HCO - 3 ) HCO - 3 loss, RF, RTA Lactat, Acetoacetic, β-hydrxybutyric acid Lactic or ketoacidosis Osmatic gape= measured osmolality- (Na+ + K+)+glucose/18+ urea/2.8 Methanol, ethylglycol or other intoxication Lab diagnostic diagnosis AG > 12mmol/l normal high High OG>10mosm/Kg normal

11. Renal Tubular acidosis Four types  Type 1. Distal renal tubular acidosis characterized by…….  Type II. Proximal renal tubular acidosis characterized by…….  Type III Mixed  Type IV

12. ANION GAP AG = Na - (Cl + HCO3). The normal plasma AG had been considered to range between 7 and 13 meq/L. knowing the normal range in a particular laboratory is often essential.

13. Calculation Anion gap AG = Na+ - (Cl- +HCO-3). 8-10mmol/l. hypoabulminaemia reduce AG. Osmotic gape (OG) =measured osmolality- calculated osmolality. <10mosm/Kg Calculated Osmolality = (Na + + K + )+glucose/18+ urea/2.8.

14. ANION GAP primarily determined by the negative charges on the plasma proteins, particularly albumin. patients with hypoalbuminemia. AG falling by about 2.5 meq/L for every 1 g/dL (10 g/L) reduction in the plasma albumin concentration.

15. ANION GAP A. an increase in the AG can be induced by a fall in unmeasured cations (hypocalcemia or hypomagnesemia) B. more commonly and more markedly, by a rise in unmeasured anions (as with hyperalbuminemia due to volume contraction or the accumulation of an organic anion in metabolic acidosis). C. Hypoalbuminemia (decreased unmeasured anions) and hyperk+ (increased unmeasured cations) lower the AG.

16. Initial screening to differentiate the high-AG acidose (1) history for evidence of drug and toxin ingestion and measurement of arterial blood gas to detect coexistent respiratory alkalosis (salicylates). (2) determination of whether diabetes mellitus is present (diabetic Ketoacidosis) (3) a search for evidence of alcoholism or increased levels of -hydroxybutyrate (alcoholic ketoacidosis) (4)observation for clinical signs of uremia and determination of the blood urea nitrogen (BUN) and creatinine (uremic acidosis) (5) Inspection of the urine for oxalate crystals (ethylene glycol). (6) Recognition of the numerous clinical settings in which lactate levels may be increased (hypotension, shock, cardiac failure, leukemia, cancer, and drug or toxin ingestion).

17. Elevated anion gap The diagnostic utility of a high AG is greatest when the AG is above 25 meq/L. Lactic acidosis, usually due to marked systemic hypoperfusion or to malignancy. Ketoacidosis due to diabetes mellitus, alcohol, or fasting, in which ß-hydroxybutyrate is the primary unmeasured anion. Is modestly in nonketotic hyperglycemia even though there is little or no metabolic acidosis. In this setting, due to the phosphate &other anions release from the cells.

18. Elevated anion gap Most of renal failure, in whom there is retention of both hydrogen and anions, such as sulfate, phosphate, and urate. Ingestion of methanol, glycolate and oxalate with ethylene glycol &aspirin. metabolic acidosis may be absent and the anion gap may be normal in methanol or ethylene glycol intoxication if there is concurrent alcohol ingestion.

19. Urinary anion gap To evaluate metabolic acidosis in normal anion gap. As to distinguish the cause is from renal or GIT ( Diarrhoea ) URINARY ANION GAP = ( Urinary Na + Urinary K ) – Urinary Cl  If –ve the cause is diarrhea GIT  If +ve the cause is distal renal tubular acidois.

20. HIGH-ANION-GAP ACIDOSES The goal is to increase the [HCO3]to 10 meq/L and the pH to 7.15, not to increase these values to normal. There are four principal causes of a high-HIGH AG acidosis: (1) lactic acidosis. (2) ketoacidosis. (3) ingested toxins. (4) acute and chronic renal failure.

23. normal anion gap metabolic acidosis U ureterosignoidostomy S saline in presence of CRI E endocrine - hypoaldosteronism D diarrhoea C carbonic anhydrase inhibitor A ammonia or alimentation eg TPN R renal tubular acidosis

24. Metabolic acidosis with High AGCause Main anion Clinic/lab Lactic acidosis. Shock, hypoxia, metformin, hepatitis. lactate Kussmaul breath Ketoacidosis. DM,alchol, hunger Acetoacetic, β- hydrxybutyric acid Kussmaul breath, Eventually coma, ketonurea Intoxications. Aspirin. methanol, ethylachol, paraldehyde Salicylic, format,glycol/ lactat, acetat High OG, ARF ARF &CRF Sulphate, phosphate S Urea, Cr. Olig/anuria

25. Metbolic acidosis with normal AG Acid infusion. - Arginin chloride. HCO 3 - loss: - Urtersigmoidostoy, ileum conduct to ureter or bladder. - Diarrhoea. - Carbonic anhydrase inhibitor. Timolol. - RTA type II. Reduced H+-secretion, NHr-excretion. - RTA typeI&IV. Reduced NH3+ formation, reduced distal Nh3+ excretion. - ARF, hypoaldosternism & hyperkalaemia.

26. Metabolic acidosis and anion gap High Anion gape M. A.Increased production of acid or acid equivalant substances Ketoacidosis: DM, Hunger, Alchol. Lactatic acidosis: Tissue hypoxia by cardiac shock, respiratory insufficiency, malignacy, liver cell failure. High A.G with normochloremic M.A.Intoxication with Methanol, Ethyle glycole,Biguanides. Decrease in acid excretion by kidney as in CRF, ARF Normal A.G metabolic acidosisRenaltubular dysfunction as in RTA Hypercholeraemic M.A.Loss of HCO3: Diarrhea, carbonic anhydrase inhibitor (dimox Ingestion of acid with chloriode

27. Clinical presentation  Tachycardia.  Breathlessness.  Low BP.  Headache.  Electrolyte disorder.  Dizziness.  Coma.

28. General principles of treatment 1 A. varies markedly with the underlying disorder. B. The aim Rx is restoration of a normal extracellular pH. C. exogenous alkali may not be required if the acidemia is not severe (arterial pH >7.20), the patient is asymptomatic, and the underlying process, such as diarrhea that can be controlled

29. General principles of treatment 2  In other settings, correction of the acidemia can be achieved more rapidly by the administration of sodium bicarbonate IV.  The initial aim of therapy is to raise the systemic pH to above 7.20; this is a level at which the major consequences of severe acidemia should not be observed.

30. HIGH-ANION-GAP ACIDOSES The goal is to increase the [HCO3]to 10 meq/L and the pH to 7.15, not to increase these values to normal. There are four principal causes of a high-HIGH AG acidosis: (1) lactic acidosis. (2) ketoacidosis. (3) ingested toxins. (4) acute and chronic renal failure.

31. Treatment Treat the underlying cause. NaHCO 3 +. Indication of NaHCO 3 + infusion. - Significant hyperkalaemia with PH < 7.1. - Bicarbonate < 8 & K + <3mmol/l substitution is given. Calculation of bicar mmol/l. Substitution= KG(kg)x0,7x(desired NaHCO3+– NaHCO3+). Haemodialysis. In severe RF or sever acidosis with hyperkalaemia

32. Calculation of bicarbonate deficit If the respiratory function is normal, pH of 7.20 usually requires raising the plasma bicarbonate to 10 to 12 meq/L. HCO3 deficit = HCO3 space xHCO3 deficit /L. Bicarbonate space =[0.4 + (2.6 ÷[HCO3]) ] x body weight ( kg). If more alkali is given, oral Nahco3 or citrate (metabolised to Hco3can replace IV therapy.

33. Treatment In server case when PH < 7.1  NaHCo3 8,4 can be given: 1ml=Immol/.  Needed NaCO3= neg. Bace excess x 0,3. Kg(KG). -divided to halfs… the last half according to ABG  Be careful about Hypokalemia and over correction. In chronic metabolic acidosis:  slow correction with oral calcium or sodium bicarbonate up to 10g/day

34. Advice In acidosis  Do not be hurry for Bicarbonate infusion before you are sure that PH of blood < 6.9 and you should contact your superior.

35. Respiratory acidosis (RA) High CO 2 and low PH. Acute RA:  Respiratory passage obstruction  cardiopulmary arrest  neuromuscular defect  restrictive LD  mechanical defect of respiration  respiratory centre defect. Chronic RA.:  COAD  lesion of respiratory centres defect  obesity  COAD  restrictive LD.

36. Treatment Acute RA.  Treat the underlying diseases.  O 2 inhalation. Chronic RA.  Therapy of the underlying disease.  Controlled O2 inhalation and slow correction.  Slow correction of PCO 2.

38. Case 1 A patient with diarrhea has an arterial pH of 7.23, bicarbonate concentration of 10 meq/L, and PCO2 of 23 mmHg. The low pH indicates acidemia, and the low plasma bicarbonate concentration indicates What?

39. 1 st Example 7.24pH 35 mmHg PCO2 90 mmHg PO2 12 mmol/L HCO3 - 10 mmol/L BE 145 mmol/L Na 4 mmol/L K 100 mmol/L Cl

40. 2 nd Example 7.30pH 40 mmHg PCO2 85 mmHg PO2 18 mmol/L HCO3 - 5 mmol/L BE 130 mmol/L Na 4 mmol/L K 104 mmol/L Cl

41. 3 rd Example 7.25pH 60 mmHg PCO2 70 mmHg PO2 22 mmol/L HCO3 - 8 mmol/L BE 139 mmol/L Na 4.3 mmol/L K 105 mmol/L Cl

42. 4 th Example 7.00pH 20 mmHg PCO2 88 mmHg PO2 13 mmol/L HCO3 - 10 mmol/L BE 139 mmol/L Na 4.3 mmol/L K 105 mmol/L Cl 5.3 mg/dl Crea. 250 mg/dl Urea 299mg%FBS

43. Thanks and good luck