BUFFERING OF HYDROGEN LOAD 1. Extracellular space minutes 2. Intracellular space minutes to hours 3. Respiratory compensation 6 to 12 hours 4. Renal compensation hours, up to 2-3 days
RENAL HYDROGEN SECRETION
HYDROGEN SECRETION (>99 %) (<1%) BICARBONATE REABSORPTION HYDROGEN EXCRETION NH 4+ (35 350 mmol/day) acidemia (+) hypokalemia (+) TITRATABLE ACID ( 25 250 mmol/day) Filtered phosphate (+) Unreabsorbable anions (+) FREE HYDROGEN ( urine ph 4.5 5.0)
HYDROGEN SECRETION STIMULATION FACTOR Decrease in plasma [HCO 3- ] Increase in plasma pco 2 SITE OF ACTION Entire nephron Entire nephron Increased filtered load of [HCO 3- ] Proximal tubule Decrease in ECF volume Hypokalemia Aldosterone Nonreabsorbable anions Proximal and collecting tubule Proximal and collecting tubule Collecting tubule Entire nephron
TYPES OF ACID-BASE DISORDERS Alkalosis and Acidosis Metabolic and Respiratory Acute and Chronic Simple and Complex
ANALYSIS OF ACID-BASE BALANCE 1. BLOOD GASOMETRY 2. SERUM ANION GAP [Na] { [Cl] + [HCO 3 ] } 3. URINE ANION GAP { [Na] + [K] } [Cl] = - [NH 4 ]
RESPIRATORY ACIDOSIS [H + ] 35-45 nmol/l [HCO 3- ] 24-26 mmol/l pco 2 40 mm Hg Diagnosis 40 24 40 NormaL
RESPIRATORY ACIDOSIS [H + ] 35-45 nmol/l [HCO 3- ] 24-26 mmol/l pco 2 40 mm Hg Diagnosis 40 24 40 NormaL 60 24 60 Acute Respiratory Acidosis
RESPIRATORY ACIDOSIS [H + ] 35-45 nmol/l [HCO 3- ] 24-26 mmol/l pco 2 40 mm Hg Diagnosis 40 24 40 NormaL 60 24 60 Acute Respiratory Acidosis 40 36 60 Compensated Respiratory Acidosis
RESPIRATORY ACIDOSIS [H + ] 35-45 nmol/l [HCO 3- ] 24-26 mmol/l pco 2 40 mm Hg Diagnosis 40 24 40 NormaL 60 24 60 Acute Respiratory Acidosis 40 36 60 Compensated Respiratory Acidosis 48 30 60 Respiratory Acidosis and Metabolic Acidosis
RESPIRATORY ACIDOSIS [H + ] 35-45 nmol/l [HCO 3- ] 24-26 mmol/l pco 2 40 mm Hg Diagnosis 40 24 40 NormaL 60 24 60 Acute Respiratory Acidosis 40 36 60 Compensated Respiratory Acidosis 48 30 60 Respiratory Acidosis and Metabolic Acidosis 32 45 60 Respiratory Acidosis and Metabolic Alkalosis
ANALYSIS OF ACID-BASE BALANCE 1. BLOOD GASOMETRY 2. SERUM ANION GAP [Na] { [Cl] + [HCO 3 ] } 3. URINE ANION GAP { [Na] + [K] } [Cl] = - [NH 4 ]
METABOLIC ACIDOSIS LACTIC ACIDOSIS -type A - caused by hypoxia - total anoxia ( 60 mmol of lactic acid/min) - type B - inadequate metabolism of lactate - liver failure - Lactic acidosis in presence of tumors: - production of LA in ischemic tumor cells - metabolites released from necrotic cells inhibit hepatic gluconeogenesis
METABOLIC ACIDOSIS 2. Ketoacidosis - accumulation of acetoacetate, β- hydroxybutyrate A. with normal β-cell function - hypoglycemia due to starvation - inhibition of insulin release (α-adrenergics) B. with abnormal β-cell function - decompensated diabetes mellitus
HYPERCHLOREMIC METABOLIC ACIDOSIS 1. Excessive loss of bicarbonates via GI tract - diarrhea ( activation of Na + /H + and Cl - /HCO 3- antiporters) 2. Excessive loss of bicarbonates via kidneys - inhibition of carbonic anhydrase - renal tubular acidosis
PROXIMAL RENAL TUBULAR ACIDOSIS (TYPE II) defective bicarbonate reabsorption due to decreased secretion of H + defect in basolateral Na + /HCO 3- cotransporter deficiency of carbonic anhydrase defect of Na + - K + ATPase the defect may coexist with: defective Na+ reabsorption defective reabsorption of other solutes (glucose, aminoacids) defective reabsorption of albumin Such disorder is called Fanconi Syndrome Fractional excretion of bicarbonates > 15%
DISTAL RENAL TUBULAR ACIDOSIS (TYPE I) defect in H + secretion from the α-intercalated cells dysfunction of HCO 3- /Cl - basolateral antiporter back-leakage of H + via hyperpermeable luminal membrane urine ph > 5.5 simultaneous increased secretion of potassium from principal cells
SYSTEMIC EFFECTS OF ACIDOSIS Cardiovascular dilatation of arteries constriction of veins negative inotropic effect release of catecholamines enhanced vagal stimulation Renal potassium wastage Central Nervous System inhibition of activity, depression Bones demineralisation
METABOLIC ALKALOSIS Patomechanisms adminstration of alkaline substances gastrointestinal H + loss contraction alkalosis metabolic alkalosis due to potassium deficiency Buffering of metabolic alkalosis ECF (about 65%) and ICF (about 35%) respiratory compensation renal compensation depends on ECF volume depends on potassium balance
SYSTEMIC EFFECTS OF ALKALOSIS Cardiovascular decreased cardiac output arrhytmias Respiratory decrease in respiratory drive increased affinity of oxygen to hemoglobin Renal decreased reabsorption of bicarbonates Central Nervous System lethargy, confusion, paresthesias
RESPIRATORY ACIDOSIS Excessive synthesis of CO 2 in the body Deficient elimination of CO 2 from the organism Patomechanisms of hypercapnia Excessive production of CO2 exercise hyperthyroidism increased body temperature carbohydrate diet all these factors do not cause hypercapnia if ventilation is adequate
RESPIRATORY ACIDOSIS - PATOMECHANISMS CENTRAL Inhibition of the medullary respiratory center ischemia barbiturates, opiates PERIPHERAL Disorders of the respiratory muscles or chest wall polimyositis myasthenia gravis hypokalemia kyphoscoliosis obesity Upper airway obstruction Impaired gas exchange in lungs obstructive lung disease adult respiratory distress syndrome pulmonary edema Mechanical hypoventilation
SYSTEMIC EFFECTS OF RESPIRATORY ACIDOSIS Acidification of cytosol => inhibition of glycolysis => inhibition of Krebs cyle => deficit of energy Cardiovascular effects negative inotropic effect vasodilatation increased blood flow in brain => brain edema (CO 2 narcosis) increased coronary blood flow ( stealing of blood from ischemic regions) intracellular acidification + increased catecholamines => arrhytmia Endocrine effects increased release of catecholamines from adrenal medulla increased release of cortisol increased release of aldosterone increased release of ACTH increased release of ADH
SYSTEMIC EFFECTS OF RESPIRATORY ACIDOSIS Gastrointestinal effects increased secretion of gastric juice Respiratory effects (if chronic) decreased sensitivity of respiratory center to CO 2 Renal increased secretion of hydrogen increased reabsorption of bicarbonates increased synthesis of NH 3 increased excretion of titratable acid
RESPIRATORY ALKALOSIS - PATOMECHANISMS Hypoxemia stimulation of the peripheral chemoreceptors => hyperventilation Pulmonary diseases hypoxemia stimulates ventilation pulmonary juxtacapillary receptors activated during edema =>n.vagus => hyper ventilation irritant receptors in bronchi => n.vagus => hyperventilation Direct stimulation of the respiratory center psychogenic or voluntary hyperventilation amines in liver failure endotoxins progesteron salicylates Mechanical hyperventilation
SYSTEMIC EFFECTS OF RESPIRATORY ALKALOSIS Alkalisation of the cells stimulation of anaerobic glycolysis leftward shift of hemoglobin curve => impaired O 2 supply to tissues Cardiovascular effects increased myocardial contractility => increased oxygen demand increased systemic vascular resistance => increased afterload arrhytmias increased platelet count & aggregation => thrombosis Respiratory effects increased airway resistance increased pulmonary capillary permeability depletion of lamellar bodies in pneumocytes => decreased compliance hypocapnia attenuates hypoxic pulmonary vasoconstriction => increased blood shunt in lungs Central Nervous System constriction of blood vessesl => decreased blood flow