Prof. M. Tatár Dept. of Pathophysiology JLF UK ACID – BASE DISORDERS Prof. M. Tatár Dept. of Pathophysiology JLF UK

  H+ affects structure and function of proteins changes of cellular enzymes activity  cellular and organ functions changes

HCO3-  H+ + CO32- HCO3- + H+  H2 CO3 acid – substance containing (H+) that can be liberated in solution (proton donor) base – substance that can combine with (H+) from a solution (proton acceptor) HCO3-  H+ + CO32- HCO3- + H+  H2 CO3

Sources of H+ in organism a) Volatile acid CO2 + H2O  H2CO3  H+ + HCO3- b) fixed acids H2SO4, H3PO4 c) organic acids lactic acid, ketoacids

Hydrogen ion [ H+ ] = 10 - 7,44 až 10 - 7,36 = 0,000000036 - 0,000000044 mol . l-1 = 36 - 44 nmol . l-1 pH = - log [ H+] mol . l-1 pH = 7,4  0,04 1.6 μm3 …… activity of 40 H+ mitochondria : 2 - 5 active H+

pH H+ (nmol.l-1) 160 140 120 100 80 acidaemia 60 norm 40 basaemia 20 6,8 7,1 7,4 7,7 acidaemia norm basaemia

acidemia - acidosis alkalemia - alkalosis

HENDERSON - HASSELBALCH equation [ H+ ] . [ HCO3-] K = --------------------- [ H2CO3] [ H2CO3] [ H+ ] = K . ---------------- [ HCO3-] 1 1 [ HCO3-] log ----- = log ----- + log ------------- [ H+ ] K [ H2CO3] [ HCO3-] pH = pK + log ------------ [ H2CO3] 24 mmol pH = 6,1 + log ----------- ( log 20 ) 1,2 mmol pH = 6,1 + 1,3 = 7,4

NL Alkalosis Acidosis Death One part of 20 parts of H2CO3 HCO3- 7,38 7,42 7,25 7,55 NL pH 6,80 Acidosis Alkalosis 7,8 7,36 7,44 Death Death One part of H2CO3 (1.2 mmol/l) PCO2 = 5.3 kPa 20 parts of HCO3- (24 mmol/l) Blood pH

NL Alkalosis Acidosis Death 1.5 part of H2CO3 (1.8 mmol/l) 7,38 7,42 7,25 7,55 NL pH 6,80 Acidosis Alkalosis 7,8 7,36 7,44 Death Death 1.5 part of H2CO3 (1.8 mmol/l) PCO2=8.0 kPa 20 parts of HCO3- (24 mmol/l) Blood pH

NL Alkalosis Acidosis Death 24 parts of HCO3- (29 mmol/l) One part of 7,38 7,42 7,25 7,55 NL pH 6,80 Acidosis Alkalosis 7,8 7,36 7,44 Death Death 24 parts of HCO3- (29 mmol/l) One part of H2CO3 (1.2 mmol/l) Blood pH

Buffers 1 [ HCO3- ] 1. Bicarbonate system ------------ [ H2 CO3 ] HCl + NaHCO3  H2 CO3 + NaCl NaOH + H2 CO3  NaHCO3 + H2O Hb 2. Hemoglobin system --------- HbO2

CO2 transport

Buffers 2 proteinate- 3. Plasma proteins --------------- H - protein HPO42- 4. Phosphate system ---------- H2PO4- HCO3- - 53% (plasma 35%, RBC- 18%) buffers Hb - HbO2 - 35% in blood Phosphates - 5% Plasm. prot. - 7%

Proximal tubule „reabsorbed“ HCO3- Na,K-ATPase

Distal nephron „new“ HCO3-

13,3 10,6 8,0 (kPa) 6,7 Pco2 5,3 4,0 2,7 7,0 7,2 7,4 7,6 pH

Mechanisms of acid – base disorders metabolic metabolic 1. acidosis 2. alkalosis 3. acidosis 4. alkalosis HCO3- pH = pK + log ---------------------- PCO2 respiratory 5. acidosis 6. alkalosis

Anion gap [ Na+ ] - ( [Cl-] + [ HCO3-] ) = 10 - 12 mmol.l-1 140 - ( 104 + 24 ) = 12 mmol.l-1

Causes of metabolic acidosis (MAC) I. Normal anion gap MAC bicarbonate loss  hyperchloremic MAC a) via the GIT: diarrhea, small bowel fistula b) kidneys: renal tubular acidosis II. High anion gap MAC gains of noncarbonic acids a)  lactic acid: hypoxia, liver insufficiency b) ketoacidosis: diabetes mellitus, starvation, etanol c) retention of fixed acids: renal failure

Compensatory response in MAC 1.  ventilation M M -----  ----- R R 2. HCO3- retention in kidneys Clinical features - Kusmaul breathing -  cardiac contractility - lethargy - renal osteodystrophy - hyperkalemia - vomiting

Causes of metabolic alkalosis (MAL) Cl- lost (hypochloremic alkalosis) a) GIT: prolonged vomiting b) urine: diuretics (furosemid) Cl- and HCO3- have a reciprocal relationships to maintaine electroneutrality

Compensatory response in MAL 1. Alveolar hypoventilation M M ------  ------- R R 2. Renal excretion of the excess HCO3- Clinical features - occasionally tetany -  risk of cardiac dysrhythmias -  afinity of Hb to O2 - hypokalemia

Causes of respiratory acidosis (RAC) Respiratory disorders  CO2 accumulation - alveolar hypoventilation Compensatory response HCO3- retention in kidneys M M -------  ------- R  R Clinical features - CNS dysfunction: confusion, somnolence - cerebral vasodilation:  intracranial pressure,

Causes of respiratory alcalosis (RAL) Alveolar hyperventilation as a result of respiratory centre stimulation a) the most common: anxiety and emotional stress b) hypermetabolic conditions: fever, CNS lesions, thyreotoxicosis c) hypoxia: pneumonia, pulmonary edema, high alitude Compensatory response Clinical features  renal excretion of HCO3- M M  ------  ------- R  R  tetany - vomiting

Mixed acid – base disorders - cardiopulmonary arrest - sepsis - pulmonary diseases and diabetes mellitus - vomiting in renal failure