ACID BASE BALANCE

1. ACID BASE BALANCE Lecture – 8 Dr. Zahoor

2. ACID BASE BALANCE • 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 H2CO3 is weak acid

3. BASE • 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) • 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 • 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 • pH 7 is neutral in CHEMISTRY • H2O pH is 7 (equal number of H+ and OH- ions are formed when H2O 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

8. ACIDOSIS & ALKALOSIS IN BODY • 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 • 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 • 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 • 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 • 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). H2CO3 : HCO3 buffer system ii). Protein buffer system iii). Hemoglobin buffer system iv). Phosphate buffer system

14. 2. Respiratory mechanism of pH control • Respiratory system regulates H+ by controlling the rate of CO2 removed • Respiration plays important role in acid base balance by pulmonary ventilation and excretion of H+ by generating CO2

15. 2. Respiratory mechanism of pH control • When there is metabolic acidosis, respiratory center in the brain stem is stimulated, therefore, increase ventilation occurs and CO2 is eliminated which helps to remove H+ ion H + HCO3 H20 + CO2 • CO2 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 • Kidneys regulate acid base balance by 1. H+ secretion and excretion 2. HCO3 reabsorption 3. Renal buffers i). Phosphate buffers ii). Ammonia mechanism

17. 3. Renal mechanism of pH control • 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 CO2 diffused into tubular cells from plasma, tubular fluid or CO2 metabolically produced in tubular cell

18. Active Secretion of H+ ion in to tubular cell and reabsorption of HCO3 ion

19. 1. H+ ion secretion • 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 HCO3

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

21. 2. HCO3 Reabsorption As we have seen in previous diagram ( slide 18 ) • Filtered HCO3 disappears, but is coupled with appearance of another HCO3 from the cell into the plasma • Two HCO3 are different, but HCO3 going to the plasma is considered to have been reabsorbed

22. 3. Renal buffers • Filtered Phosphate buffer • 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 (NaHPO4-) and Generation of “New” HCO3-

24. Secreted ammonia as Urinary Buffer • When acidosis exist, the tubular cells secrete NH3 in the tubular fluid, once normal urinary phosphate buffers are saturated • NH3 is synthesized from amino acid glutamine within the tubular cell • NH3 combines with H+ in the tubular fluid to form ammonium (NH4) • NH4 is excreted from tubular fluid

25. Production and Secretion of NH4+ and HCO3- by ProximalTubular Cell “New” HCO3-

26. Buffering of Hydrogen Ion Secretion by Ammonia (NH3) in the Collecting Tubules

27. pH Regulation • 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 • In Alkalosis, H+ ion is secreted less in PCT and type A intercalated cells • There is decreased HCO3 reabsorption • Secretion of HCO3 occurs by intercalated type B-cells in DCT and CT. HCO3 is excreted in urine. • In Alkalosis, kidney makes urine alkaline

30. ACID BASE DISORDERS • Acid Base imbalance can occur from respiratory dysfunction or metabolic disturbances • Acid Base disorders - Respiratory acidosis – increased CO2 - Respiratory alkalosis – decreased CO2 - Metabolic acidosis – decreased HCO3 - Metabolic alkalosis – increased HCO3 There can be combined disorders

31. ACID BASE DISORDERS Respiratory Acidosis • Occurs due to CO2 retention, therefore, there is increased CO2 due to hypoventilation • Increased CO2 generates more H+ ion • Causes - Depression of respiratory center e.g. drugs - Nerve and muscle disorders

32. ACID BASE DISORDERS Respiratory Alkalosis • Occurs due to decreased CO2 e.g. hyperventilation, therefore, decreased H+ is formed • Causes of Respiratory Alkalosis - Fever - Anxiety - Aspirin poisoning - High altitude

33. ACID BASE DISORDERS Metabolic Acidosis • It is characterized by decreased HCO3 • CO2 remains normal • Causes of Metabolic Acidosis - Severe Diarrhea – HCO3 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 Metabolic Alkalosis • In Metabolic Alkalosis, there is increased HCO3 and decreased H+ ion • Causes - Vomiting – Loss of H ion due to loss of gastric juice - Ingestion of alkaline drugs e.g. NaHCO3 for acidity

35. pH in Uncompensated Acid-Base Abnormalities

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

37. THANK YOU