1. Acid-Base Balance Disturbances

2. 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 Hydrogen ion homeostasis

3. Volatile acids 1- Volatile acids: Carbon Dioxide CO2 (H2CO3) - Carbon Dioxide CO2 (H2CO3) Nonvolatile acids 2- Nonvolatile acids: 1- Organic acids 1- Organic acids: Lactic Acid - Lactic Acid Ketone bodies - Ketone bodies 2-Inorganic acids 2- Inorganic acids Sulphuric Acid - Sulphuric Acid - Phosphoric Acid - Phosphoric Acid Sources of acids of blood

4. 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 Buffering of acids (H+) in blood

5. The equilibrium reactions of the buffer system H + HCO 3 - H 2 CO 3 (Reaction 1) H + + HCO 3 - H 2 CO 3 (Reaction 1) H 2 CO 3 CO (Reaction 2) H 2 CO 3 CO 2 + H 2 O (Reaction 2) excreted by the lung excreted by the lungs Accordingly, the addition of H + causes the equilibrium to be shifted to the right (towards CO 2 production and excretion by the lungs) Carbonic Acid - Bicarbonate Buffer System ( H 2 CO 3 – HCO 3 - )

6. HCO 3 - H 2 CO 3 (Reaction 1) H + + HCO 3 - H 2 CO 3 (Reaction 1) H 2 CO 3 CO(Reaction 2) H 2 CO 3 CO 2 + H 2 O (Reaction 2) First Stage: pHnot In this case, pH of blood may be within normal range i.e. not much affected bufferCOMPENSATED ACIDOSIS However, amount of buffer (HCO3-) is reduced (COMPENSATED ACIDOSIS) End Stage: buffer pHacidemia UNCOMPENDSATED ACIDOSIS 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) H 2 CO 3 - HCO 3 - buffer In case of increased H+ production, H 2 CO 3 - HCO 3 - buffer will reduce H+ as follows: Carbonic Acid - Bicarbonate Buffer System ( H 2 CO 3 – HCO 3 - ) ( H 2 CO 3 – HCO 3 - ) cont.

7. Disorders of Acid-Base Balance acidosis)  Increase in H + concentrations results in a decrease in pH of blood (acidosis) alkalosis)  Decrease in H + concentrations results in an increase in pH of blood (alkalosis) Alkalosis or Acidosis H + whether Alkalosis or Acidosis describes any abnormality in H + balance whether : Compensated Alkalosis or Acidosis 1- Compensated Alkalosis or Acidosis  No blood pH changes pH of blood is within normal range  No blood pH changes (pH of blood is within normal range).  Buffer concentrations are abnormal  Compensatory mechanisms  Compensatory mechanisms try to restore pH to normal if pH is changed. 2-Uncompensated alkalosis or acidosis (alkalaemia or acidaemia) 2- Uncompensated alkalosis or acidosis (alkalaemia or acidaemia)  AbnormalpH of blood (above or below normal range)  Abnormal pH of blood (above or below normal range)  Buffer concentrations are abnormal

8. Relation between pH & buffer Henderson-Hasselbach Equation [HCO 3 - ] [HCO 3 - ] pH pH = 6.1 + log --------------------------------- pCO 2 pCO 2 + 0.225 Assessment of Acid-Base Balance 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

9. Blood pH & bicarbonate buffer are to be measured Bicarbonate buffer measurement: 1- INDIRECTLY From arterial blood sample From arterial blood sample Using blood gas analyzer to measure pH & PCO2 in arterial blood Accordingly, bicarbonate in blood can be measured indirectly by applying Henderson- Hasselbach Equation 2- DIRECTLY From venous blood Samples From venous blood Samples: HCO 3 - directly used to measure HCO 3 - directly Assessment of Acid-Base Balance Assessment of Acid-Base Balance cont. [HCO 3 - ] [HCO 3 - ] pH pH = 6.1 + log --------------------------------- PCO 2 PCO 2 + 0.225

10. Acid-base 1- Acidosis: - Metabolic - Metabolic - Respiratory - Respiratory 2- Alkalosis: - Metabolic - Metabolic - Respiratory - Respiratory DIAGNOSIS IS CONFIRMED BY LABORATORY INVESTIGATIONS OF pH, pCO2 & pO2 & HCO3- Sample: Arterial Blood using Procedure: Blood gas analysis Acid-Base Balance Disturbances

11. Metabolic Acidosis 1- Metabolic Acidosis Causes Causes : Increased production of H + 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

12. Mechanism Mechanism : The more decrease in HCO 3 - in blood leads to finally end in an decrease in pH as follows: [HCO 3 - ] pH = 6.1 + Log ---------------------- PCO 2 X 0.225 Metabolic Acidosis Metabolic Acidosis cont. H+ is increased. It reacts with HCO3-. HCO3- is reduced. CO2 is produced then exhaled by lungs (increase respiration) H + HCO 3 - H 2 CO 3 (Reaction 1) HCO3- is reduced. CO2 is produced then exhaled by lungs (increase respiration) H + + HCO 3 - H 2 CO 3 (Reaction 1) H 2 CO 3 CO 2 (Reaction 2) H 2 CO 3 CO 2 + H 2 O (Reaction 2) CO 2 is produced (increased) & then exhaled by lungs (increase respiration) CO 2 is produced (increased) & then exhaled by lungs (increase respiration)

13. Compensatory mechanisms of metabolic acidosis 1- Exhaustion of bicarbonate buffer with shift of reactions to CO2 production. respiratory Stimulation of the respiratory centre to eliminate excess CO2 formed 2- Increase in renal acid excretion of H + Metabolic Acidosis Metabolic Acidosis cont

14. LABORTORY INVESTIGATION: SampleArterial Blood Sample: Arterial Blood EquipmentBlood Gas Analyzer Equipment: Blood Gas Analyzer pH : Low HCO3: Low PCO2 : Low: CO2 is produced then exhaled by lungs by increasing respiration PCO2 : Low: as CO2 is produced then exhaled by lungs by increasing respiration PO2: Normal

15. Causes Causes Impaired carbon dioxide excretion and thus blood pCO2 increases. hypoventilation caused by any pulmonary (lung) cause resulting in hypoventilation. 1-Chronic respiratory acidosischronic obstructive airway diseases. 1-Chronic respiratory acidosis: occurs due to chronic obstructive airway diseases. Chronic bronchitis Emphysema Bronchial asthma 2-Acute respiratory acidosisacute respiratory failure 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 2- Respiratory Acidosis

16. Mechanism: The increase in pCO2 in blood leads to an decrease in pH as follows: [HCO 3 - ] pH = 6.1 + Log ---------------------- PCO 2 X 0.225 Respiratory Acidosis CO 2 is increased in blood (due to respiratory disease). So, the reaction is directed as follows COH 2 CO 3 (Reaction 1) H 2 CO 3 H + HCO 3 - (Reaction 2) H+ is produced & pH is decreased (acidosis) CO 2 is increased in blood (due to respiratory disease). So, the reaction is directed as follows CO 2 + H 2 O H 2 CO 3 (Reaction 1) H 2 CO 3 H + + HCO 3 - (Reaction 2) H+ is produced & pH is decreased (acidosis)

17. LABORTORY INVESTIGATION: SampleArterial Blood Sample: Arterial Blood EquipmentBlood Gas Analyzer Equipment: Blood Gas Analyzer pH: Low HCO3: High PCO2: High (due to the respiratory problem) PO2 : Low (due to the respiratory problem) Compensation: by kidney via ↑ HCO3- reabsorption ↑ H+ excretion

18. The primary abnormality in metabolic alkalosis is the increased plasma bicarbonate level. (HCO3-). 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: kidneys 1- From the kidneys (increased excretion of acids, H + ions): a- Mineralcorticoid (aldosterone) excess b- Severe potassium deficiency GIT 2- From the GIT (increased loss acids, H + ions): vomiting and gastric wash 3-Metabolic ALkalosis

19. Mechanism Mechanism : The increase in HCO 3 - in blood leads to an increase in pH as follows: [HCO 3 - ] pH = 6.1 + Log ---------------------- PCO 2 X 0.225 Metabolic ALkalosis H+ is reduced. So, the reaction is directed as follows CO2 production is increased by respiratory depression (compensatory) COH 2 CO 3 (Reaction 1) H 2 CO 3 H + HCO 3 - (Reaction 2) HCO 3 - is produced & pH is increased (alkalosis) H+ is reduced. So, the reaction is directed as follows CO2 production is increased by respiratory depression (compensatory) CO 2 + H 2 O H 2 CO 3 (Reaction 1) H 2 CO 3 H + + HCO 3 - (Reaction 2) HCO 3 - is produced & pH is increased (alkalosis)

20. LABORTORY INVESTIGATION: SampleArterial Blood Sample: Arterial Blood EquipmentBlood Gas Analyzer Equipment: Blood Gas Analyzer pH: High HCO3: High PCO2 : High (due to compensatory respiratory depression) Compensation: by lungs via inhibition of respiration which leads to ↑ PCO2 Compensation: by lungs via inhibition of respiration which leads to ↑ PCO2

21. 4- Respiratory Alkalosis Causes : Hyperventilation The PCO 2 is reduced due to: Hyperventilation which may be due to: Respiratory centre stimulation as in cases of 1- Respiratory centre stimulation as in cases of: Anxiety Salicylate overdose Cerebral disease (infection, tumour) pulmonary embolism. 2- pulmonary embolism. Fevers 3- Fevers Hepatic failure 4- Hepatic failure Mechanism The decrease in PCO 2 leads to an increase in pH as follows: [HCO 3 - ] pH = 6.1 + Log ---------------------- PCO 2 X 0.225

22. CO2 is decreased. So, the reaction is as follows to produce CO2: H + HCO 3 - H 2 CO 3 (Reaction 1) So, the reaction is as follows to produce CO2: H + + HCO 3 - H 2 CO 3 (Reaction 1) H 2 CO 3 CO 2 (Reaction 2) H 2 CO 3 CO 2 + H 2 O (Reaction 2) Compensation : by kidney by ↓ HCO3 reabsorption and ↓ H+ secretion LABORTORY INVESTIGATION: SampleArterial Blood Sample: Arterial Blood EquipmentBlood Gas Analyzer Equipment: Blood Gas Analyzer pH: High HCO3: Low PCO2 : Low Respiratory Alkalosis