1. Respiratory regulation of Acid-Base Balance DR. SUMREENA MANSOOR ASSISTANT PROF OF BIOCHEMISTRY DEPT OF BIOCHEMISTRY & MOLECULAR BIOLOGY

2. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. pH Review

3. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. The Body and pH

4. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Acids are H + donors. Bases are H + acceptors, or give up OH - in solution. Acids and bases can be: Strong – dissociate completely in solution HCl, NaOH Weak – dissociate only partially in solution Lactic acid, carbonic acid

5. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Types of Acids in the Body Volatile acids: Can leave solution and enter the atmosphere. H 2 C0 3 (carbonic acid). Pco 2 is most important factor in pH of body tissues.

6. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Types of Acids in the Body Fixed Acids: Acids that do not leave solution. Sulfuric and phosphoric acid. Catabolism of amino acids, nucleic acids, and phospholipids.

7. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Types of Acids in the Body Organic Acids: Byproducts of aerobic metabolism, during anaerobic metabolism and during starvation, diabetes. Lactic acid, ketones.

8. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Small changes in pH can produce major disturbances Most enzymes function only with narrow pH ranges Acid-base balance can also affect electrolytes (Na +, K +, Cl - ) Can also affect hormones

9. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. The body produces more acids than bases Acids take in with foods Acids produced by metabolism of lipids and proteins Cellular metabolism produces CO 2. CO 2 + H 2 0 ↔ H 2 CO 3 ↔ H + + HCO 3 -

10. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Henderson-Hasselbalch Equation

11. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. APPLICATIONS OF HH EQUATION Analysis of dissociation of the alanine in the same way as described for acetic acid Use to calculate how pH of a physiologic solution responds to changes in the concentration of a week acid and/or it’s corresponding salt form. Example Bicarbonate buffer system (How HCO 3 and CO 2 Influence pH)

12. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. APPLICATIONS OF HH EQUATION Useful for calculating ionic forms of acidic and basic drugs. Acidic drug HA H + +A - Example: Aspirin  Basic drug BH + B+H + Example: Morphine  Drug can readily pass through the membrane if it is uncharged

13. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. APPLICATIONS OF HH EQUATION How much drug is found on either side of a membrane that separates two compartments that differ in pH, for example, the stomach (pH 1.0-1.5) and blood plasma (pH 7.4)

14. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Buffer Systems Provide or remove H + and stabilize the pH. Include weak acids that can donate H + and weak bases that can absorb H +. Change in pH, after addition of acid, is less than it would be in the absence of buffer.

15. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chemical Buffers Act within fraction of a second. Protein. HCO 3 -. Phosphate.

16. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Proteins COOH or NH 2. Largest pool of buffers in the body. pKa close to plasma. Albumin, globulins such as Hb.

17. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Protein Buffers Includes hemoglobin, work in blood Carboxyl group gives up H + Amino Group accepts H + Glutamate, aspartate, histidine, arginine, lysine Additional potentially charged groups in side chain

18. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Bicarbonate buffer 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

19. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. HCO 3 - pk= 6.1 Most important ECF buffer. Present in large quantities. Respiratory and renal systems act on this buffer system.

20. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Phosphate buffer Major intracellular buffer H + + HPO 4 2- ↔ H 2 PO4 - OH - + H 2 PO 4 - ↔ H 2 O + HPO 4 2- pk = 6.8 Better buffer in ICF (kidneys and bone)

21. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Rates of correction Buffers function almost instantaneously Respiratory mechanisms take several minutes to hours Renal mechanisms may take several hours to days

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23. Respiratory System 2nd line of defense. Acts within min. maximal in 12-24 hrs. H 2 CO 3 produced converted to CO 2, and excreted by the lungs. Powerful, but works with volatile acids Exhalation of carbon dioxide. CO 2 + H 2 0 ↔ H 2 CO 3 ↔ H + + HCO 3 - Body pH can be adjusted by changing rate and depth of breathing

24. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Renal system Can eliminate large amounts of acid Can conserve and produce bicarbonate ions Most effective regulator of pH If kidneys fail pH balance fails

25. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Urinary Buffers Urine pH = 4.5 H + secreted into the urine tubule and combines with HPO 4 -2 or NH 3. HPO 4 -2 + H + H 2 PO 4 -2 NH 3 + H + NH 4 +

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27. Acid-Base Imbalances 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.

28. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Compensation If underlying problem is metabolic, hyperventilation or hypoventilation can help : respiratory compensation If problem is respiratory, renal mechanisms can bring about metabolic compensation

29. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Acidosis 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

30. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Alkalosis Alkalosis can cause It can cause : Nervousness Muscle spasms or tetany Convulsions Loss of consciousness Death

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32. Respiratory Acidosis 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

33. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Respiratory Acidosis Acute conditions: Adult Respiratory Distress Syndrome Pulmonary edema Pneumothorax

34. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Compensation for Respiratory Acidosis Kidneys eliminate hydrogen ion and retain bicarbonate ion Acute respiratory failure: pH low,[HCO - 3 ] high normal, or slightly raised Chronic respiratory failure: pH normal or low depending upon chronicity,[HCO - 3 ] raised

35. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Signs and Symptoms of Respiratory Acidosis Breathlessness Restlessness Lethargy and disorientation Tremors, convulsions, coma Respiratory rate rapid then gradually depressed Skin warm and flushed due to vasodilatation caused by excess CO 2

36. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Treatment of Respiratory Acidosis Restore ventilation Treat underlying dysfunction or disease

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38. Respiratory Alkalosis Carbonic acid deficit pCO 2 less than 35 mm Hg (hypocapnea) Primary cause is hyperventilation

39. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Respiratory Alkalosis Conditions that stimulate respiratory center: Hysterical over breathing (overrides normal respiratory control) Raised ICP (Which stimulate respiratory centre) Hypoxia Pulmonary edema Lobar pneumonia Pulmonary collapse or fibrosis Excessive artificial ventilation

40. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Compensation of Respiratory Alkalosis Compensatory fall in plasma [HCO - 3 ] tends to correct the pH Pco 2 always reduced [HCO - 3 ] low normal or low pH raised (uncompensated or partly compensated) or normal (fully compensated)

41. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Treatment of Respiratory Alkalosis Treat underlying cause IV Chloride containing solution – Cl - ions replace lost bicarbonate ions

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