1. ACID BASE BALANCE Lecture – 8 Dr. Zahoor 1

2. ACID BASE BALANCE 2  Acid Base Balance refers to regulation of free (unbound) H + concentration in the body fluids  Acids liberate free H + ion, whereas bases accept them  Strong acid gives greater percentage of free H + e.g. HCL is strong acid  Weak acid give less H + ion e.g. carbonic acid H 2 CO 3 is weak acid

3. BASE 3  Base is a substance that combines with free H + and removes it from the solution  Strong base combines with H + more readily than weak base

4. pH (Potential Hydrogen) 4  pH is used to express H + ion present  H + in ECF is normally 4×10 -8 or 0.00000004 equivalent per liter (3 million times less than Na + in ECF)  pH = log1/[H + ]  High H + corresponds to low pH (acidity)  Low H + corresponds to high pH (towards alkaline)

5. pH 5  Normal pH = 7.4  How it is calculated ?  Normal H+ ion concentration is 40nEq/L and can change normally 3-5nEq/L  These small values are difficult to express, therefore we express H+ concentration on logarithm scale using pH units  pH = log 1/[H+] OR pH= -log H+  Normal H+ is 40nEq/L (0.00000004Eq/L)  Therefore Normal pH = - log [ 0.00000004]  pH = 7.4

6. Acid Base Balance 6  pH 7 is neutral in CHEMISTRY  H 2 O pH is 7 (equal number of H + and OH - ions are formed when H 2 O disassociates)  Solution having pH less than 7.0 is acidic (have more H + ion)  Solution having pH more than 7.0 is alkaline (less H + ion)

7. pH consideration in chemistry and physiology 7

8. ACIDOSIS & ALKALOSIS IN BODY 8  Arterial blood pH is 7.45  Venous blood pH is 7.35  Average blood pH is 7.4  Acidosis when blood pH falls below 7.35  Alkalosis when blood pH is above 7.45 Remember – Reference point for body’s pH determination is 7.4. Why?

9. ACIDOSIS & ALKALOSIS IN BODY 9  Because body’s pH of 7.4 is taken neutral for the body and is reference point for acidosis or alkalosis for the body.  PH compatible with life 6.8- 8  IMPORTANT – An arterial pH less than 6.8 or greater than 8.0 is not compatible with life Death can occur in few seconds, therefore, pH of body fluids is carefully regulated

10. ACIDOSIS & ALKALOSIS IN BODY 10  pH regulation is important because changes in H +, alter nerve, enzyme and K + activity which will affect CVS, CNS and body metabolic processes  Acidosis causes depression of CNS, disorientation, coma and death  Alkalosis causes over excitability of CNS and peripheral nervous system (muscle twitches and muscle spasm)

11. REGULATION OF H + ION IN THE BODY 11  There are 3 lines of defense against changes in H + ion to keep the pH of ECF 7.4 in the body  3 lines of defense are: 1. Chemical buffer system – respond in seconds 2. Respiratory mechanism of pH control – respond in minutes 3. Renal mechanism of pH control – respond in hours to days We will study each one, mainly renal mechanisms

12. REGULATION OF H + ION IN THE BODY 12 1. Chemical Buffer System  In Chemical Buffer System either an acid or a base is added or removed from the solution  In body, 4 buffer systems are i). H 2 CO 3 : HCO 3 buffer system ii). Protein buffer system iii). Hemoglobin buffer system iv). Phosphate buffer system

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14. 2. Respiratory mechanism of pH control 14  Respiratory system regulates H+ by controlling the rate of CO 2 removed  Respiration plays important role in acid base balance by pulmonary ventilation and excretion of H+ by generating CO 2

15. 2. Respiratory mechanism of pH control 15  When there is metabolic acidosis, respiratory center in the brain stem is stimulated, therefore, increase ventilation occurs and CO 2 is eliminated which helps to remove H+ ion H + HCO 3  H 2 0 + CO 2  CO 2 is removed by ventilation, therefore, decreased H+ occurs in body fluid  Respiratory system is very important for every day removal of H+ ion  Respiratory system can bring pH back to normal only 50 to 75%

16. 3. Renal mechanism of pH control 16  Kidneys regulate acid base balance by 1. H+ secretion and excretion 2. HCO 3 reabsorption 3. Renal buffers i). Phosphate buffers ii). Ammonia mechanism

17. 3. Renal mechanism of pH control 17 1. H + ion secretion  The proximal, distal and collecting tubule all secrete H + ion  Normally urine pH is 6 as H + is excreted  Mechanism of H + ion secretion H + secretary process begins in the tubular cells with CO 2 diffused into tubular cells from plasma, tubular fluid or CO 2 metabolically produced in tubular cell

18. 18 Active Secretion of H+ ion in to tubular cell and reabsorption of HCO 3 ion

19. 1. H + ion secretion 19  H+ ion is secreted in PCT by both primary H+ ATP pump and secondary active transport via Na + - H + anti-porters (anti-porters transport Na + and H + in opposite directions where Na + is reabsorbed and H + is secreted)  H+ secretion in distal and collecting tubule occurs in intercalated cells type A  Intercalated cells type A secrete H+ ion and reabsorb HCO 3

20. 20 Primary Active Secretion of H+ ion in the intercalated epithelial Type A cell in DCT and CT

21. 2. HCO 3 Reabsorption 21 As we have seen in previous diagram ( slide 18 )  Filtered HCO 3 disappears, but is coupled with appearance of another HCO 3 from the cell into the plasma  Two HCO 3 are different, but HCO 3 going to the plasma is considered to have been reabsorbed

22. 3. Renal buffers 22 i) Filtered Phosphate buffer ii) Secreted ammonia Filtered Phosphate buffer  Secreted H+ ion is buffered by phosphate buffer system  H+ secreted in the tubule combines with phosphate

23. Buffering of Secreted H + by Filtered phosphate (NaHPO 4 - ) and Generation of “New” HCO 3 - 23

24. Secreted ammonia as Urinary Buffer 24  When acidosis exist, the tubular cells secrete NH 3 in the tubular fluid, once normal urinary phosphate buffers are saturated  NH 3 is synthesized from amino acid glutamine within the tubular cell  NH 3 combines with H+ in the tubular fluid to form ammonium (NH 4 )  NH 4 is excreted from tubular fluid

25. Production and Secretion of NH 4 + and HCO 3 - by Proximal Tubular Cell “New” HCO 3 - 25

26. Buffering of Hydrogen Ion Secretion by Ammonia (NH 3 ) in the Collecting Tubules 26

27. pH Regulation 27  Kidneys are powerful third line of defense against changes in H+ ion  Kidneys requires hours to days to compensate for changes in body fluid pH  H+ is secreted by energy depending H+ carrier until tubular fluid (urine) becomes 800 times more acidic than plasma  At this point, kidney can not acidify urine any more and pH of urine is 4.5

28. pH Regulation 28  In Alkalosis, H+ ion is secreted less in PCT and type A intercalated cells  There is decreased HCO 3 reabsorption  Secretion of HCO 3 occurs by intercalated type B-cells in DCT and CT. HCO 3 is excreted in urine.  In Alkalosis, kidney makes urine alkaline

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30. ACID BASE DISORDERS 30  Acid Base imbalance can occur from respiratory dysfunction or metabolic disturbances  Acid Base disorders - Respiratory acidosis – increased CO 2 - Respiratory alkalosis – decreased CO 2 - Metabolic acidosis – decreased HCO 3 - Metabolic alkalosis – increased HCO 3 There can be combined disorders

31. ACID BASE DISORDERS 31 Respiratory Acidosis  Occurs due to CO 2 retention, therefore, there is increased CO 2 due to hypoventilation  Increased CO 2 generates more H+ ion  Causes - Depression of respiratory center e.g. drugs - Nerve and muscle disorders

32. ACID BASE DISORDERS 32 Respiratory Alkalosis  Occurs due to decreased CO 2 e.g. hyperventilation, therefore, decreased H+ is formed  Causes of Respiratory Alkalosis - Fever - Anxiety - Aspirin poisoning - High altitude

33. ACID BASE DISORDERS 33 Metabolic Acidosis  It is characterized by decreased HCO 3  CO 2 remains normal  Causes of Metabolic Acidosis - Severe Diarrhea – HCO 3 is lost from GIT - Diabetes mellitus – there is keto acidosis due to abnormal fat metabolism - Renal failure – kidney can not excrete H+ ion, therefore, there is increase H+ ion

34. ACID BASE DISORDERS 34 Metabolic Alkalosis  In Metabolic Alkalosis, there is increased HCO 3 and decreased H+ ion  Causes - Vomiting – Loss of H ion due to loss of gastric juice - Ingestion of alkaline drugs e.g. NaHCO 3 for acidity

35. 35 pH in Uncompensated Acid-Base Abnormalities

36. 36 Analysis of Simple Acid-Base Disorders Analysis of Simple Acid-Base Disorders Figure 30-10; Guyton and Hall

37. THANK YOU 37