Acid-Base Balance PDF

Acid – base balance Asst.Prof.Dr.Qasim AL-Daami Basic facts – repetition Regulation of A-B balance Pathophysiology of clinically important disorders Acids vs. Bases  definition: Bronsted-Lowry (1923) Acid: H+ donor  normal...

Acid – base balance Asst.Prof.Dr.Qasim AL-Daami Basic facts – repetition Regulation of A-B balance Pathophysiology of clinically important disorders Acids vs. Bases  definition: Bronsted-Lowry (1923) Acid: H+ donor  normal A:B ratio  1:20 Base: H+ acceptor strength is defined in terms of the tendency to donate (or accept) the hydrogen ion to (from) the solvent (i.e. water in biological systems) pH  pH is and indirect measure of [H+] pH=-log [H+] E CAVE! Hydrogen ions (i.e. protons) do not exist free in solution but are linked to adjacent water molecules by hydrogen bonds (H3O+) [H+] by a factor of 2 causes a  pH of 0.3 pH 7.40  40 nM pH 7.00  100 nM pH 7.36  44 nM  neutral vs. normal plasma pH pH 7.44  36 nM pH 7.4 (7.36-7.44) normal pH 7.0 neutral but fatal!!! Buffers  extracellular  intracellular carbonic acid / proteins bicarbonate (H2CO3 / phosphoric acid / HCO3-) hydrogen phosphate Henderson-Hasselbalch equation: (H3PO4 / H2PO4- + pH = 6.1 + log([HCO3-] / 0.03 pCO2) HPO42-) haemoglobin Organs involved in the regulation of A-B-balance Equilibrium with plasma High buffer capacity  Haemoglobin – main buffer for CO2 Excretion of CO2 by alveolar ventilation: minimally 12,000 mmol/day Reabsorption of filtered bicarbonate: 4,000 to 5,000 mmol/day Excretion of the fixed acids (acid anion and associated H+): about 100 mmol/day Organs involved in the regulation of A-B-balance CO2 production from complete oxidation of substrates  20% of the body’s daily production metabolism of organic acid anions  such as lactate, ketones and amino acids metabolism of ammonium  conversion of NH4+ to urea in the liver results in an equivalent production of H+ Production of plasma proteins  esp. albumin contributing to the anion gap Bone inorganic matrix consists of hydroxyapatite crystals (Ca10(PO4)6(OH)2]  bone can take up H+ in exchange for Ca2+, Na+ and K+ (ionic exchange) or release of HCO3-, CO3- or HPO42- pH is constantly “impaired” by metabolism Total CO2: = [HCO3] + [H2CO3] + [carbamino CO2] + [dissolved CO2] Why is pH so important ?  All the known low molecular weight and water soluble biosynthetic intermediates possess groups that are essentially completely ionised at neutral pH’ E pH-dependent ionisation (i.e. charge) serves to an efficient intracellular trapping of ionised compounds within the cell and its organelles  Exceptions: macromolecules (proteins)  mostly charged anyway or size-trapping or hydrophobic lipids  those needed intarcellularly are protein-bound waste products  pH has an effects on protein function The most important pH for the body is the intracellular pH The most important pH for the body is the intracellular pH  Intracellular pH is maintained at about the pH of neutrality (6.8 at 37˚C) because this is the pH at which metabolite intermediates are all charged and trapped inside the cell pN [H+] = [OH-] pN=7.0 at 25˚C for pure H2O pN=6.8 at 37˚C in cell  Extracellular pH is higher by 0.5 to 0.6 pH units and this represents about a fourfold gradient favouring the exit of hydrogen ion from the cell E to maintain it at a stable value because of the powerful effects of intracellular [H+] on metabolism maintaining a stable intracellular pH by:  ‘Intracellular buffering’ (chemical, metabolic, organelles)  Adjustment of arterial pCO2  Loss of fixed acids from the cell into the extracellular fluid Respiratory system - CO2  differences in the stimulation of respiration by pCO2, H+ and pO2  alveolar ventilation  disturbances acidemia  respiratory centre of the brain  alveolar ventilation  CO2 alkalemia  respiratory centre of the brain   alveolar ventilation   CO2 Renal system – fixed H+ & HCO3-  Proximal tubular  Distal tubular mechanisms: mechanisms: reabsorption of HCO3- net excretion of H+ filtered at the  normally 70mmol/day glomerulus  max. 700mmol/day production of NH4+ E together with proximal tubule excretion of H+ could increase up to 1000x!!! (pH of urine 4.5) Formation of titratable acidity (TA) Addition of NH4+ to luminal fluid Reabsorption of remaining HCO3- Assessment of A-B balance Arterial blood Mixed venous blood range range pH 7.40 7.35-7.45 pH 7.33-7.43 pCO 40 mmHg 35 – 45 pCO2 41 – 51 pO2 95 mmHg 80 – 95 pO2 35 – 49 Saturation 95 % 80 – 95 Saturation 70 – 75 BE 2 BE HCO3- 24 mEq/l 22 - 26 HCO3- 24 - 28 Disorders of A-B balance  Acidosis: abnormal condition lowering arterial pH before secondary changes in response to the primary aetiological factor  Alkalosis: abnormal condition raising arterial pH before secondary changes in response to the primary aetiological factor  Simple A-B disorders: there is a single primary aetiological acid-base disorder  Mixed A-B disorders: more primary aetiological disorders are present simultaneously Acidaemia: arterial pH44 nM) Alkalaemia: arterial pH>7.44 (i.e. [H+]40 mmHg), i.e. hypercapnia  time course: paCO2 = VCO2 / VA acute (pH) chronic (pH or normalisation of pH)  renal compensation – retention of HCO3-, 3-4 days  causes: decreased alveolar ventilation (presence of excess CO2 in the inspired gas) (increased production of CO2 by the body) Most cases of RA are due to decreased alveolar ventilation !!!! the defect leading to this can occur at any level in the respiratory control mechanism A rise in arterial pCO2 is a potent stimulus to ventilation so a respiratory acidosis will rapidly correct unless some abnormal factor is maintaining the hypoventilation RA - inadequate alveolar ventilation  Central respiratory depression &  Lung or chest wall defects other CNS problems acute on COPD drug depression of respiratory chest trauma -contusion, center (e.g. by opiates, sedatives, haemothorax anaesthetics) pneumothorax CNS trauma, infarct, haemorrhage diaphragmatic paralysis or tumour pulmonary oedema hypoventilation of obesity (e.g. Pickwick syndrome) adult respiratory distress syndrome cervical cord trauma or lesions (at or above C4 level) restrictive lung disease high central neural blockade aspiration poliomyelitis tetanus  Airway disorders cardiac arrest with cerebral upper airway obstruction hypoxia laryngospasm bronchospasm / asthma  Nerve or muscle disorders Guillain-Barre syndrome  External factors Myasthenia gravis Inadequate mechanical ventilation muscle relaxant drugs toxins e.g. organophosphates, snake venom various myopathies RA - rare causes  Over-production of CO2 in hypercatabolic disorders malignant hyperthermia sepsis  Increased intake of CO2 re-breathing of CO2-containing expired gas addition of CO2 to inspired gas insufflation of CO2 into body cavity (e.g. for laparoscopic surgery) RA - metabolic effects (hypercapnia!)  depression of intracellular metabolism  cerebral effects  cardiovascular system extremely high hypercapnia:  anaesthetic effects (pCO2>100mmHg)  hypoxaemia An arterial pCO2>90 mmHg is not compatible with life in patients breathing room air: pAO2 = [0.21x(760-47)]-90/0.8 = 37 mmHg RA - compensation  Acute RA - buffering only!  Chronic RA - renal about 99% of this bicarbonate retention buffering occurs takes 3 or 4 days to reach intracellularly its maximum  proteins (haemoglobin paCO2 pCO2 in and phosphates) are the proximal tubular cells most important intravascular buffers for H+ secretion into the CO2 but their lumen: concentration is low   HCO3 production which relative to the amount of crosses the basolateral carbon dioxide requiring membrane and enters the buffering circulation (so plasma [HCO3] increases) the bicarbonate system is not responsible for any   Na+ reabsorption in exchange for H+ buffering of a respiratory acid-base disorder -   NH3 production to 'buffer' the H+ in the system cannot buffer itself tubular lumen (so urinary excretion of NH4Cl increases) RA - correction (i.e. treatment)  the pCO2 rapidly returns to normal with restoration of adequate alveolar ventilation E treatment needs to be directed to correction of the primary cause if this is possible  rapid fall in pCO2 (especially if the RA has been present for some time) can result in: severe hypotension ‘post hypercapnic alkalosis’ Metabolic acidosis (MA)  primary disorder is a pH due to HCO3-:  fixed [H+] = high anion gap loss or  reabsorption of HCO3- = normal anion gap AG = [Na+] - [Cl-] - [HCO3-] MA - causes  ketoacidosis  renal tubular acidosis diabetic, alcoholic,  GIT loss of HCO3 starvation diarrhoea  lactic acidosis drainage of pancreatic or  acute renal failure bile juice  toxins MA - metabolic effects  respiratory hyperventilation shift of haemoglobin dissociation curve to the right decreased 2,3 DPG levels in red cells (shifting the ODC back to the left)  cardiovascular  others increased bone resorption (chronic acidosis only) shift of K+ out of cells causing hyperkalaemia