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Acid-Base Balance Disorders LECTURE FROM PATHOPHYSIOLOGY 2012/2013 OLIVER RÁCZ & EVA LOVÁSOVÁ INSTITUTE OF PATHOPHYSIOLOGY UPJŠ LF KOŠICE 23. 5. 2017 abre.ppt 1 Introductory remarks Acidobasic balance (ABB) First of all ABB of extracellular space – blood 7,4 = 40 nmol/l H+ (or 4*10-7 mol/l ) (not H+ but H3O+) CO2 production: 20 mols/day (300 – 360 l) Strong (non-volatile) acid production: 60 – 70 mmols/day oxidation of SH groups (amino acids): sulfate hydrolysis of proteins, phospholipids: phospate keto acids, lactic acid... 23. 5. 2017 abre.ppt 2 Logarithms [H+] Exp pH pH nmol/l mmol/l 100 mmol/l -1 1 7,1 79 10 mmol/l -2 2 7,2 63 1 mmol/l -3 3 7,3 50 100 mmol/l -4 4 7,4 40 10 mmol/l -5 5 7,5 31 1 mmol/l -6 6 7,6 25 100 nmol/l -7 7 7,7 20 10 nmol/l -8 8 7,8 16 1 nmol/l -9 9 abre.ppt 7,9 12 23. 5. 2017 3 Physiological a pathological values Blood Physical exercise Frontiers of life Urine Red cells Muscle cells Bile Duodenal juice Prostata cells Gastric juice 23. 5. 2017 pH 7,36 - 7,44 7,10 6,80 - 7,70 H+ nmol/l 44 - 36 94 158 - 20 4,50 - 8,00 32000 – 10 7,28 6,90 6,2 - 8,5 6,5 - 7,6 4,50 1,2 - 3,0 53 126 631 - 3 316 - 25 32 mmol/l 1000 - 63 abre.ppt 4 ABB Measurement Not very long ago... 23. 5. 2017 abre.ppt 5 „Astrup” Arterial or arterialised capillary blood (hyperemisation of finger or auricle) 0,1 ml into heparinised capillary tube without air, immediate measurement pH and pCO2 electrochemically pCO2 5,3 ± 0,53 kPa 1,2 ± 0,12 mmol/l Other – calculated actual bicarbonates 24 ± 2 mmol/l anion gap 9 – 17 mmol/l standard bicarbonates as actual base excess 0 ± 2 mmol/l buffer base 49 ± 3 23. 5. 2017 abre.ppt 6 Buffers and regulatory systems Buffers only absorb the attacks of hydrogen ions and prevent sudden big fluctuations of pH. Closed systems hydrogencarbonate phosphate haemoglobin/protein bones (carbonate) Regulatory systems – open, regulate the hydrogencarbonate system respiratory (provisional, delayed) excretory (definite) 23. 5. 2017 abre.ppt 7 23. 5. 2017 abre.ppt 8 Henderson and Hasselblach pH = pK + log [HCO3]/[CO2] pK = 6,1 HCO3 = 24 mmol/l CO2 = 40 mmHg = 5,3 kPa = 1,2 mmol/l pH = 6,1 + log (24/1,2) = 6,1 + 1,3 pH = 7,4 23. 5. 2017 abre.ppt 9 Simple ABR disorders acidosis pH < 7,35 metabolic HCO3 < 22 respiratory CO2 > 5,8 alkalosis pH > 7,45 metabolic HCO3 > 26 respiratory CO2 < 4,8 Acute and chronic Not compensated, partial compensated, corriged 23. 5. 2017 abre.ppt 10 Henderson and Hasselblach 1 metabolic acidosis – something is decreasing bicarbonate (24) HCO3 = 12 mmol/l CO2 = 1,2 mmol/l pH = 6,1 + log (12/1,2) = 6,1 + 1,0 pH = 7,1 COMPENSATION THROUGH HYPERVENTILATION (CO2 OUT) HCO3 = 12 mmol/l CO2 = 0,6 mmol/l pH = 6,1 + log (12/0,6) = 6,1 + 1,3 pH = 7,4 is everything OK??? 23. 5. 2017 abre.ppt 11 Henderson and Hasselblach 2 metabolic alkalosis – too much of bicaarbonate HCO3 = 36 mmol/l CO2 = 1,2 mmol/l pH = 6,1 + log (36/1,2) = 6,1 + 1,5 pH = 7,6 COMPENSATION THROUGH HYPOVENTILATION (CO2) RETENTION HCO3 = 36 mmol/l CO2 = 1,8 mmol/l pH = 6,1 + log (36/1,8) = 6,1 + 1,3 pH = 7,4 is everything OK??? 23. 5. 2017 abre.ppt 12 Henderson and Hasselblach 3 respiratory acidosis – asfyxia HCO3 = 24 mmol/l CO2 = 2,4 mmol/l pH = 6,1 + log (24/2,4) = 6,1 + 1,0 pH = 7,1 COMPENSATION THROUGH ACID EXCRETION HCO3 = 48 mmol/l CO2 = 2,4 mmol/l pH = 6,1 + log (48/2,4) = 6,1 + 1,3 pH = 7,4 is everything OK??? 23. 5. 2017 abre.ppt 13 Henderson and Hasselblach 4 respiratory alkalosis – histeria, mountain sickness HCO3 = 24 mmol/l CO2 = 0,8 mmol/l pH = 6,1 + log (24/0,8) = 6,1 + 1,5 pH = 7,6 COMPENSATION THROUGH ACID RETENTION HCO3 = 16 mmol/l CO2 = 0,8 mmol/l pH = 6,1 + log (16/0,8) = 6,1 + 1,3 pH = 7,4 is everything OK??? 23. 5. 2017 abre.ppt 14 Acids bind and decrease bicarbonate Respiratory insufficiency increases CO2 Increased bicarbonate Decreased CO2 20 HCO3 MAC RAC MAL RAL 1 CO2 7,4 23. 5. 2017 abre.ppt 15 RAC, MAC, RAL, MAL 7,2 7,3 CO2 7,4 7,5 7,6 23. 5. 2017 abre.ppt HCO3 16 Compensation 7,2 7,3 CO2 7,4 7,5 7,6 23. 5. 2017 abre.ppt HCO3 17 Compensated disorders 7,2 7,3 CO2 7,4 7,5 7,6 23. 5. 2017 abre.ppt HCO3 18 Respiratory compensation of MAC Exspiration of CO2 (Kussmaul) balances the decreased bicarbonate Delayed – respiration reacts to pH in the brain Danger – delay also during treatment: HCO3 and pH restored through treatment Hyperventilation persists Respiratory alkalosis! 23. 5. 2017 abre.ppt 19 Kidneys Synthesis of bicarbonate in renal tubular cells H20 + CO2 H2CO3 H+ + -HCO3 Complete resorbtion of bicarbonate into blood Maximal excretion of H+ through exchange for Na+, K+ and by protone pump In filtrate H+ ions associate with ammonia and primary phosphate H+ + NH3 = NH4+ 23. 5. 2017 H+ + HPO42- = H2PO4abre.ppt 20 Metabolic acidosis pH < 7,35; HCO3 < 22 mmol/l Increased production of endogenous acids – diabetic ketoacidosis, lactic acidosis Exogenous acids or compounds metabolised to acids – ethylene glycol, methanol, salicylate Bicarbonate losses through GIT or kidneys (diarrhoe, intestinal fistulae, kidney diseases) Insufficient excretion of H+ in acute or chronic kidney failure and in some hereditary tubulopathies 23. 5. 2017 abre.ppt 21 Severity of metabolic acidosis pH HCO3 Light 7,35 – 7,30 22 – 20 Medium 7,30 – 7,20 20 – 16 Severe 7,20 – 7,10 16 – 10 < 7,10 < 10 Very severe 23. 5. 2017 abre.ppt 22 Ketones ? Lactate ? Other ? Anion gap 15 25 AG HCO3- 15 25 15 15 140 110 100 Na+ 100 Cl- 1: norma, anion gap 15 mmol/l 2: MAC, bicarbonate ,chloride , anion gap 15 mmol/l 3: MAC, bicarbonate ,chloride norm, anion gap 23. 5. 2017 abre.ppt 23 Ketoacidosis during starvation Lipid catabolism Gluconeogenesis from oxalacetate, an important intermediate od Krebs cycle Accumulation of acetylcoenzyme A Ketonemia without hyperglycaemia Decreased albumin, phosphate depletion 23. 5. 2017 abre.ppt 24 Diabetic ketoacidosis I (cell starvation) Nondiagnosed Type 1 DM, increased insulin demand during intercurrent diseases Hyperglycaemia Polyuria and dehydratation (glycosuria) Lipid degradation, gluconeogenesis, Krebs cycle blockade Ketonemia, ketonuria (instead of nitroprusside test specific b-hydroxybutyrate assay – in blood, too) Kussmaul breathing, disturbed consciousness, coma Increased anion gap 23. 5. 2017 abre.ppt 25 Diabetic ketoacidosis II (electrolyte disorder) Hyponatremia, hypophosphatemia Intracellular potassium depletion due to insulin deficiency outflow of K+ from cells (acidosis) Urinary losses of K+ (osmotic diuresis, RAA system activation in dehydration) Not always connected with hypokalemia Dangerous hypokalemia can occur during too rapid treatment with insulin FOLLOW IT! 23. 5. 2017 abre.ppt 26 Ketoacidosis in alcohol, methanol and ethylene glycol intoxication Ethanol acetaldehyde, b-hydroxybutyrate (AG) and thiamin deficiency (coenzyme of pyruvate dehydrogenase) Hypalbuminemia, hypomagnesemia Tissue hypoxia (lactic acid) But: vomitus leads to MAL Methanol formaldehyde, formic acid (AG) Optic nerve (alcohol dehydrogenase) Ethanol as treatment Ethylene glycol glyoxal, oxalic acid (AG) Acute tubular necrosis 23. 5. 2017 27 Treatment: dialysis andabre.ppt ethanol Lactic acidosis Hypoxia (A) or block of degradation (B) A – respiratory diseases, circulatory failure, anaemia. With RAC B – some oral antidiabetics of biguanide type (withdrawn or strict indication – contraindications), fructose, sorbitol B – some malignancies, thiamin deficiency hereditary enzyme defects (G6PD) Norm < 1,3 mmol/l > 5 mmol/l high mortality 23. 5. 2017 abre.ppt 28 Acidosis in kidney failure Simple principle – decrease of glomerular filtration < 0,3 ml/s (n = 2 ml/s*) the kidneys are not able to resorb bicarbonate and excrete acids Complicated reality – adaptory mechanisms of tubuli / damage of tubuli Anion gap phosphates potassium Dialysis 23. 5. 2017 abre.ppt 29 MAC with normal anion gap (hyperchloremic) Bicarbonate losses through GIT (diarrhoe) Renal tubular acidoses RTA II – proximal type RTA I – distal type RTA III – mixed RTA IV – with hyperkalemia 23. 5. 2017 abre.ppt 30 Acids and aldehydes Formic acid and formaldehyde, (from methanol) CH3OH H2C=O HCOOH Acetic acid and acetaldehyde (from ethanol) C2H5OH CH3-HCO CH3-COOH Oxalic acid and glyoxal (from ethylene glycol “antifreeze”) HOCH2-CH2OH OHC-CHO HOOC-COOH Lactic acid (from glycolysis) CH3-CHOH-COOH b-hyrdroxybutyric, acetoacetic acid and acetone (stravation, insulin deficiency) CH3-CHOH-CH2-COOH, CH3-CO-CH2-COOH, CH3-CO-CH3 23. 5. 2017 abre.ppt 31 Metabolic alkalosis pH > 7,45; HCO3- > 26 mmol/l Decrease of extracellular space volume Metabolites smaller space and increased K+ and H + secretion due to activation of renin-angiotensin-aldosterone system, Na reabsorbtion, hypokaliemia citrate from blood transfusions, milk alkali syndrome, metabolites of ketone bodies Mineralocorticoids – Na+ retention, K+ and H+ depletion Chloride depletion – diuretics, vomitus, Mg deficiency Dg. 23. help: Urinary chloride excretion < or > 10 mmol/day32 5. 2017 abre.ppt Respiratory acidosis pH < 7,35; pCO2 > 5,8 kPa Connection between ABR and tissue oxygen supply – remember haemoglobin dissociation curve CO2 in red cells is rapidly converted (carboanhydrase) to H2CO3 which dissociates to H+ and HCO3Respiration is regulated by pH and pCO2 RAC – in respiratory disorders (as a part of global respiratory insufficiency) and in hemodynamic failure Renal compensation is not complete Tisue hypoxia leads to lactate acidosis 23. 5. 2017 abre.ppt 33 Respiratory alkalosis pH > 7,45; pCO2 < 4,8 kPa Hyperventilation psychogenic, fever, G negative sepsis mountain disease, CO intoxication some drugs – aminophyllin, salicylate some lungs diseases – pulm. embolism Parestesia, cramps, arrhythmias (ionized Ca++) 23. 5. 2017 abre.ppt 34