1. 1 Mohammed A. Almeziny BPharm.RPh. Msc. PhD Clinical Pharmacist

2.  Homeostasis of pH is tightly controlled  Extracellular fluid = 7.4  Blood = 7.35 – 7.45  8.0 death occurs  Acidosis (acidemia) below 7.35  Alkalosis (alkalemia) above 7.45 2

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4.  Most enzymes function only with narrow pH ranges  Acid-base balance can also affect electrolytes (Na +, K +, Cl - )  Can also affect hormones 4

5.  Cardiovascular  (e.g., impaired contractility, arrhythmias),  Pulmonary  (e.g., impaired oxygen delivery, respiratory muscle fatigue, dyspnea),  Renal  (e.g., hypokalemia)  Neurologic  (e.g., decreased cerebral blood flow, seizures, coma).

6.  Acids take in with foods  Acids produced by metabolism of lipids and proteins  Cellular metabolism produces CO 2. 6

7. Balance maintained by:  Buffering systems  Lungs  Kidneys H 2 CO 3 …..HCO 3

8. 1-Buffer systems  Prevent major changes in pH  Act as sponges…  3 main systems Bicarbonate-carbonic acid buffer Phosphate buffer Protein buffer H+

9.  Sodium Bicarbonate (NaHCO 3 ) and carbonic acid (H 2 CO 3 )  Maintain a 20:1 ratio : HCO 3 - : H 2 CO 3 HCl + NaHCO 3 ↔ H 2 CO 3 + NaCl NaOH + H 2 CO 3 ↔ NaHCO 3 + H 2 O 9

10.  Major intracellular buffer  H + + HPO 4 2- ↔ H 2 PO4 -  OH - + H 2 PO 4 - ↔ H 2 O + H 2 PO 4 2- 10

11.  Includes hemoglobin, work in blood and ISF  Carboxyl group gives up H +  Amino Group accepts H + 11

12.  Exhalation of carbon dioxide  respiratory control center in the medulla to increase the rate and depth of ventilation.  Peripheral chemoreceptors (located in the carotid arteries and the aorta)  activated by arterial acidosis, hypercarbia (elevated PaCO 2 ), and hypoxemia (decreased PaO 2 ).  Central chemoreceptors (located in the medulla).  activated by cerebrospinal fluid (CSF) acidosis and by elevated carbon dioxide tension in the CSF 12

13.  Powerful, but only works with volatile acids  Doesn’t affect fixed acids like lactic acid  CO 2 + H 2 0 ↔ H 2 CO 3 ↔ H + + HCO 3 -  Body pH can be adjusted by changing rate and depth of breathing 13

14.  Can eliminate large amounts of acid  Can also excrete base  Can conserve and produce bicarb ions  Most effective regulator of pH  If kidneys fail, pH balance fails 14

15.  Buffers function almost instantaneously  Respiratory mechanisms take several minutes to hours  Renal mechanisms may take several hours to days 15

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17.  pH< 7.35 acidosis  pH > 7.45 alkalosis  The body response to acid-base imbalance is called compensation  May be complete if brought back within normal limits  Partial compensation if range is still outside norms. 17

18.  If underlying problem is metabolic, hyperventilation or hypoventilation can help : respiratory compensation.  If problem is respiratory, renal mechanisms can bring about metabolic compensation. 18

19.  Principal effect of acidosis is depression of the CNS through ↓ in synaptic transmission.  Generalized weakness  Deranged CNS function the greatest threat  Severe acidosis causes  Disorientation  coma  death 19

20.  Alkalosis causes over excitability of the central and peripheral nervous systems.  Numbness  Lightheadedness  It can cause :  Nervousness  muscle spasms or tetany  Convulsions  Loss of consciousness  Death 20

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22.  Respiratory Acidosis  Respiratory Alkalosis  Metabolic Acidosis  Metabolic Alkalosis

23.  Carbonic acid excess caused by blood levels of CO 2 above 45 mm Hg.  Hypercapnia – high levels of CO 2 in blood  Chronic conditions:  Depression of respiratory center in brain that controls breathing rate – drugs or head trauma  Paralysis of respiratory or chest muscles  Emphysema 23

24.  Acute conditons:  Adult Respiratory Distress Syndrome  Pulmonary edema  Pneumothorax 24

25.  Kidneys eliminate hydrogen ion and retain bicarbonate ion 25

26.  Breathlessness  Restlessness  Lethargy and disorientation  Tremors, convulsions, coma  Respiratory rate rapid, then gradually depressed  Skin warm and flushed due to vasodilation caused by excess CO 2 26

27.  Restore ventilation  Treat underlying dysfunction or disease 27

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29.  Carbonic acid deficit  pCO 2 less than 35 mm Hg (hypocapnea)  Most common acid-base imbalance  Primary cause is hyperventilation 29

30.  Conditions that stimulate respiratory center:  Oxygen deficiency at high altitudes  Pulmonary disease and Congestive heart failure – caused by hypoxia  Acute anxiety  Fever, anemia  Early salicylate intoxication  Cirrhosis  Gram-negative sepsis 30

31.  Kidneys conserve hydrogen ion  Excrete bicarbonate ion 31

32.  Treat underlying cause  Breathe into a paper bag  IV Chloride containing solution – Cl - ions replace lost bicarbonate ions 32

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34.  Bicarbonate deficit - blood concentrations of bicarb drop below 22mEq/L  Causes:  Loss of bicarbonate through diarrhea or renal dysfunction  Accumulation of acids (lactic acid or ketones)  Failure of kidneys to excrete H+ 34

35. Normal AG  Hypokalemic  Diarrhea  Fistulous disease  Ureteral diversions  Type 1 RTA  Type 2 RTA  Carbonic anhydrase inhibitors  Hyperkalemic  Hypoaldosteronism  Hydrochloric acid or precursor  Type 4 RTA  Potassium-sparing diuretics  Amiloride  Spironolactone  Triamterene Elevated AG  Renal Failure  Lactic Acidosis (see Table 10-5)  Ketoacidosis  Starvation  Ethanol  Diabetes mellitus  Drug Intoxications  Ethylene glycol  Methanol  Salicylates AG, anion gap; RTA, renal tubular acidosis.

36.  Headache, lethargy  Nausea, vomiting, diarrhea  Coma  Death 36

37.  Increased ventilation  Renal excretion of hydrogen ions if possible  K + exchanges with excess H + in ECF  ( H + into cells, K + out of cells) 37

38.  Treat underlying cause  IV Bicarbonate solution 38

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40.  Bicarbonate excess - concentration in blood is greater than 26 mEq/L  Causes:  Excess vomiting = loss of stomach acid  Excessive use of alkaline drugs  Certain diuretics  Endocrine disorders  Heavy ingestion of antacids  Severe dehydration 40

41.  Respiratory compensation difficult – hypoventilation limited by hypoxia 41

42.  Respiration slow and shallow  Hyperactive reflexes ; tetany  Often related to depletion of electrolytes  Atrial tachycardia  Dysrhythmias 42

43.  Treat underlying disorder  Electrolytes to replace those lost  IV chloride containing solution  0.1 N HCL  Infusion rate 0.2 mmol/kg/hr  Central line  Acetazolamide 43

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45. Disorder Arterial pH Primary Change Compensatory Change Metabolic acidosis ↓↓HCO 3 - ↓PaCO 2 Respiratory acidosis ↓↑PaCO 2 - ↑HCO 3 - Metabolic alkalosis ↑↑HCO 3 - ↑PaCO 2 Respiratory alkalosis ↑↓PaCO 2 - ↓HCO 3 -

46.  Arterial Blood Gas (ABG)  Arterial carbon dioxide tension (PaCO 2 ).  Serum bicarbonate (HCO 3 - ).  Arterial oxygen tension (PaO 2 )  pH  <7.35, the patient is considered academic  >7.45, the patient is considered alkalemic

47. ABGsNormal Range pH7.36–7.44 PaO 2 90–100 mmHg PaCO 2 35–45 mmHg HCO 3 - 22–26 mEq/L

48.  The concentration of all the unmeasured anions in the plasma eg lactate, acetoacetate, sulphate.  Anion gap = [Na+] - [Cl-] - [HCO3-]  Reference range is 8 to 16 mmol/l.  Adjusted AG = AG + 2.5 × (normal albumin – measured albumin in g/dL

49.  Clinical Use of the Anion Gap  To signal the presence of a metabolic acidosis and confirm other findings  Help differentiate between causes of a metabolic acidosis  To assist in assessing the biochemical severity of the acidosis and follow the response to treatment

50.  Osmolality mOsm/kg H2O= (1.86[Na])+([glucose (mmol/L)])+([BUN mmol/L])  Osmolal gap= measured Osmolality- Calculated Osmolality  exists when the measured and calculated values differ by >10 mOsm/kg

51.  Obtain a detailed patient history and clinical assessment.  Check the arterial blood gas, sodium, chloride, and HCO 3 -. Identify all abnormalities in pH, PaCO 2, and HCO 3 -.

52.  Determine which abnormalities are primary and which are compensatory based on pH.  If the pH is <7.40, then a respiratory or metabolic acidosis is primary.  If the pH is >7.40, then a respiratory or metabolic alkalosis is primary.  If the pH is normal (7.40) and there are abnormalities in PaCO 2 and HCO 3 -, a mixed disorder is probably present because metabolic and respiratory compensations rarely return the pH to normal.

53.  Consider other laboratory tests to further differentiate the cause of the disorder.  If the AG is normal, consider calculating the urine AG.  If the AGis high and a toxic ingestion is expected, calculate an osmolal gap.  If the AG is high, measure serum ketones and lactate.

54.  Always calculate the AG. If ≥20, a clinically important metabolic acidosis is usually present even if the pH is within a normal range.  If the AG is increased, calculate the excess AG(AG-10). Add this value to the HCO 3 - to obtain corrected value.  If corrected value >26, a metabolic alkalosis is also present.  If corrected value is <22, a nonanion gap metabolic acidosis is also present.

55.  Consider other laboratory tests to further differentiate the cause of the disorder.  If the AG is normal, consider calculating the urine AG.  If the AGis high and a toxic ingestion is expected, calculate an osmolal gap.  If the AG is high, measure serum ketones and lactate.

56.  Compare the identified disorders to the patient history and begin patient-specific therapy.

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