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Acid-Base Balance Disturbances. Hydrogen ion h omeostasis. Acids are produced continuously during normal metabolism. (provide H+ to blood) H + ion concentration of blood varies between narrow limits pH of the extracellular fluid = 7.35 – 7.45
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Hydrogen ion homeostasis • Acids are produced continuously during normal metabolism. • (provide H+ to blood) • H+ ion concentration of blood varies between narrow limits pH of the extracellular fluid = 7.35 – 7.45 • Constant H+ concentration within physiological limits is physiologically • important to preserve the enzyme activity and metabolism
Sources of acids of blood • 1- Volatile acids: - Carbon Dioxide CO2 (H2CO3) 2- Nonvolatile acids: 1- Organic acids: - Lactic Acid - Ketone bodies 2-Inorganic acids - Sulphuric Acid - Phosphoric Acid
Buffering of acids (H+) in blood • H+ is generated during intracellular metabolism from several sources(~ 150 000 mmol H+ is produced every day) • They are continuously neutralized by buffers resulting in no gain of H+ ions = No pH change
Carbonic Acid -Bicarbonate Buffer System • ( H2CO3 – HCO3-) The equilibrium reactions of the buffer system H+ + HCO3-H2CO3(Reaction 1) H2CO3CO2+ H2O(Reaction 2) excreted by the lungs Accordingly,the addition of H+ causes the equilibrium to be shifted to the right (towards CO2production and excretion by the lungs)
Carbonic Acid -Bicarbonate Buffer System • ( H2CO3 – HCO3-) cont. In case of increased H+ production, H2CO3- HCO3-bufferwill reduce H+ as follows: • H+ + HCO3-H2CO3(Reaction 1) • H2CO3CO2+ H2O (Reaction 2) First Stage: In this case, pH of blood may be within normal range i.e. not much affected However, amount of buffer (HCO3-) is reduced (COMPENSATED ACIDOSIS) End Stage: Continuous reduction of H+ will lead to continuous reduction of buffer (HCO3-) will finally end in lowering pH of blood to below normal limits i.e. acidemia (UNCOMPENDSATED ACIDOSIS)
Disorders of Acid-Base Balance • Increase in H+ concentrations results in a decrease in pH of blood (acidosis) • Decrease in H+concentrations results in an increase in pH of blood (alkalosis) Alkalosis or Acidosisdescribes any abnormality in H+ balance whether: 1- Compensated Alkalosis or Acidosis • Noblood pH changes (pH of blood is within normal range). • Buffer concentrations are abnormal • Compensatory mechanisms try to restore pH to normal if pH is changed. 2-Uncompensated alkalosis or acidosis (alkalaemiaoracidaemia) • AbnormalpHof blood (above or below normal range) • Buffer concentrations are abnormal
Relation between pH & buffer Assessment of Acid-Base Balance Henderson-Hasselbach Equation Normal pH of blood is not an indication of acid-base balance. Accordingly, in order to assess acid-base balance (status) of blood , we should assess pH& buffer concentration of blood [HCO3-] pH= 6.1 + log --------------------------------- pCO2+ 0.225
Assessment of Acid-Base Balance cont. Blood pH & bicarbonate buffer are to be measured Bicarbonate buffer measurement: 1- INDIRECTLY From arterial blood sample Using blood gas analyzer to measure pH& PCO2in arterial blood Accordingly, bicarbonatein blood can be measured indirectly by applying Henderson-Hasselbach Equation 2- DIRECTLY From venous blood Samples: used to measure HCO3-directly [HCO3-] pH= 6.1 + log --------------------------------- PCO2+ 0.225
Acid-Base Balance Disturbances Acid-base 1- Acidosis: - Metabolic - Respiratory 2- Alkalosis: - Metabolic - Respiratory DIAGNOSIS IS CONFIRMED BY LABORATORY INVESTIGATIONS OF pH, pCO2 & pO2 & HCO3- Sample: Arterial Blood using Procedure: Blood gas analysis
1-Metabolic Acidosis Causes: I-Increased production of H+ Common Causes of increased H+ (acids) in the blood: 1- Increased endogenous acid production. - Diabetic ketoacidosis (increased ketone bodies in blood) - Lactic acidosis (increased lactic acid in blood). 2-Ingestion of acids (or substance that produces an acid) - Poisons: as salicylate (aspirin) overdose - Methanol ingestion - High protein diet. 3-decreased acid (H+) excretion by the kidney: in renal failure. II- Loss of bicarbonate: e.g. in diarrhea
Metabolic Acidosis cont. Mechanism: The more decrease in HCO3- in blood leads to finally end in an decrease in pH as follows: [HCO3-] pH = 6.1 + Log ---------------------- PCO2 X 0.225 H+ is increased. It reacts with HCO3-. HCO3- is reduced.CO2 is produced {then exhaled by lungs (increase respiration)H++ HCO3-H2CO3(Reaction 1) H2CO3CO2+ H2O (Reaction 2) CO2 is produced (increased) & then exhaled by lungs (increase respiration)
Metabolic Acidosis cont Compensatory mechanisms of metabolic acidosis 1- Exhaustion of bicarbonate buffer with shift of reactions to CO2 production. Stimulation of the respiratorycentre to eliminate excess CO2 formed 2- Increase in renal acid excretion of H+
LABORTORY INVESTIGATION: Sample: Arterial Blood Equipment: Blood Gas Analyzer pH: Low HCO3: Low PCO2: Low: asCO2 is produced then exhaled by lungs by increasing respiration PO2: Normal
2-Respiratory Acidosis Causes Impaired carbon dioxide excretion and thus blood pCO2increases. caused by any pulmonary (lung) cause resulting in hypoventilation. 1-Chronic respiratory acidosis: occurs due to chronic obstructive airway diseases. Chronic bronchitis Emphysema Bronchial asthma 2-Acute respiratory acidosis: occurs due to acute respiratory failure Cardiac arrest Neuromuscular disorders of chest wall Depression of the respiratory centre in the brain by: cerebral disease or drugs
Respiratory Acidosis Mechanism: The increase in pCO2 in blood leads to an decrease in pH as follows: [HCO3-] pH = 6.1 + Log ---------------------- PCO2 X 0.225 CO2 is increased in blood (due to respiratory disease). So, the reaction is directed as followsCO2+ H2OH2CO3(Reaction 1)H2CO3H+ + HCO3-(Reaction 2)H+ is produced & pH is decreased (acidosis)
Compensation:by kidney via ↑ HCO3- reabsorption ↑ H+ excretion LABORTORY INVESTIGATION: Sample: Arterial Blood Equipment: Blood Gas Analyzer pH: Low HCO3: High PCO2: High (due to the respiratory problem) PO2 : Low (due to the respiratory problem)
3-Metabolic ALkalosis The primary abnormality in metabolic alkalosis is the increased plasma bicarbonate level. (HCO3-). Causes: Less common 1- Intake of a large amounts of alkali as sodium bicarbonate: (if intake is more than 1000 mmol/day) More common 2- Loss of H+ (acids) from the body: 1- From the kidneys(increased excretion of acids, H+ ions): a- Mineralcorticoid (aldeserone) excess b- Severe potassium deficiency 2- From the GIT(increased loss acids, H+ ions): vomiting and gastric wash
Metabolic ALkalosis Mechanism: The increase in HCO3- in blood leads to an increase in pH as follows: [HCO3-] pH = 6.1 + Log ---------------------- PCO2 X 0.225 H+ is reduced. So, the reaction is directed as followsCO2 production is increased by respiratory depression (compensatory)CO2+ H2O H2CO3(Reaction 1)H2CO3H+ + HCO3-(Reaction 2)HCO3-is produced & pH is increased (alkalosis)
Compensation: by lungs via inhibition of respiration which leads to ↑ PCO2 LABORTORY INVESTIGATION: Sample: Arterial Blood Equipment: Blood Gas Analyzer pH: High HCO3: High PCO2 : High (due to compensatory respiratory depression)
4- Respiratory Alkalosis Causes: The PCO2 is reduced due to: Hyperventilationwhich may be due to: 1- Respiratory centre stimulation as in cases of: Anxiety Salicylateoverdose Cerebral disease (infection, tumour) 2- pulmonary embolism. 3- Fevers 4- Hepatic failure Mechanism The decrease in PCO2 leads to an increase in pHas follows: [HCO3-] pH = 6.1 + Log ---------------------- PCO2 X 0.225
Respiratory Alkalosis CO2 is decreased. So, the reaction is as follows to produce CO2:H++ HCO3-H2CO3(Reaction 1) H2CO3CO2+ H2O (Reaction 2) Compensation : by kidney by ↓ HCO3 reabsorption and ↓ H+ secretion LABORTORY INVESTIGATION: Sample: Arterial Blood Equipment: Blood Gas Analyzer pH: High HCO3: Low PCO2 : Low