Buffers in the body

a detailed information abour buffers and its importance

1. BUFFERS IN THE BODY 1 PRESENTOR : Dr.Kumar MODERATOR : Dr.Prabhavathy

2. 2 Buffers resist changes in pH from the addition of acid or base in the body absorb H 3 O + or OH  from foods and cellular processes to maintain pH are important in the proper functioning of cells and blood in blood maintain a pH close to 7.4; a change in the pH of the blood affects the uptake of oxygen and cellular processes

3. Buffers (continued) When an acid or base is added to water, the pH changes drastically to a buffer solution, the pH does not change very much; pH is maintained 3

4. Components of a Buffer 4 The components of a buffer solution are acid – base conjugate pairs can be a weak acid and a salt of its conjugate base typically have equal concentrations of the weak acid and its salt can also be a weak base and a salt of its conjugate acid

5. The Major Body Buffer Systems

6. Body Buffer system

7. -Hydrogen ion Homeostasis -Control system -Control CO2 (PCO2) By lungs -Control HCO3 - By Kidney and Erythrocytes

8. Body Buffer system Hydrogen Ion Homeostasis About 50 to100 m mol of hydrogen ions are released from cells into extracellular fluid each day Hydrogen ion concentration [H + ] is maintained between about 35 and 45 nano mol\L. ( 40nmol/L=pH 7.4) Control of hydrogen ion balance depends on the secretion of H + from the body, mainly into the urine therefore Renal impairment causes acidosis

9. -Aerobic metabolism of the carbon skeletons of organic compounds converts from hydrogen, carbon and oxygen to water and carbon dioxide (CO 2 ) 9 C C C C C C H H H H H H H H H H H H

10. CO 2 is essential compound of extracellular buffering system -Control of CO 2 depends on normal lung function.

11. Buffering Is a process by which a strong acid (or base) is replaced by a weaker one, with a consequent reduction in the number of free hydrogen ions and therefore the change in PH HCl + NaHCO 3 = H2CO 3 + NaCl Strong acid buffer weak acid neutral salt

12. PH is a measure of hydrogen ion activity Log 100 =log 10 2 =2 Log 10 7 =7 If [H + ] is 10 -7 (0.000 0001) Then log [H + ] =-7 The Henderson – hasselbalch equation PH= PK+log [base] /[acid]

13. The bicarbonate pair is an important biological buffer example; H 2 CO 3 HCO 3 - + H + Acid base The base is bicarbonate (HCO 3 - ) and the carbonic acid (H 2 CO 3 ) . - It is not possible to measure the latter directly however it is in equilibrium with dissolved CO 2 of which the partial pressure (PCO 2 ) can be estimated.

14. The conc. of H 2 CO 3 is derived by multiplying this measured value by the solubility co efficient (s) for CO 2 therefore PH =PK-log [HCO 3 - ]/PCO 2 XS (0.03 )

15. Hydrogen ion Homeostasis PH is relatively tightly controlled in blood by the following mechanisms 1-Hydrogen ions can be incorporated in water H + + HCO 3 - H 2 CO 3 CO 2 + H 2 O

16. This is normal mechanism during oxidative phos phorylation . H + is inactivated by combining with the HCO3 only if the reaction is driven to the right by the removal of CO 2 . By this would cause bicarbonate depletion H + can be lost from the body only through the kidney and the intestine .This mechanism is coupled with the generation of bicarbonate ion (HCO 3 - ) In the kidney this is the method which secretion of excess H + ensures regeneration of buffering capacity

17. Control system CO 2 and H + are potentially toxic products of aerobic and anaerobic metabolism most CO 2 is lost through the lungs but some is converted to bicarbonate Thus contributing important extracellular buffering capacity Bicarbonate system is the most important buffer in the body because has high capacity.

18. The control of CO 2 (PCO 2 ) by the Respiratory center and lungs The partial pressure of CO 2 in plasma is normally about 5.3 kpa (40 mmHg) and depend on the balance between the rate of production by metabolism and the loss through the pulmonary .

19. the rate of respiration, and then therefore the rate of CO 2 elemination is controlled by chemoreceptor in the respiratory centre in the medulla of the brain. The receptors respond to changes in the [CO 2 ]or[H + ] of plasma or of the cerebrospinal fluid . the PCO 2 rises much above 40 mm of Hg the PH falls, the rate of respiration increases .

20. Normal lungs have a very large reserve capacity for CO 2 elimination The normal respiratory centre and lungs can control CO 2 conc. Within norrow limits by responding to changes in the [H + ] and therefore compensate for changes in acid-base disturbances . diseases of the lungs, or abnormalities of respiratory control, primarily affect the PCO 2

21. The Control of Bicarbonate by -The Kidneys and Erythrocytes The renal tubular cells and erythrocytes generate bicarbonate, the buffer base in the bicarbonate system from CO 2 under physiological conditions.

22. The erythrocyte mechanism makes fine adjustments to the plasma bicarbonate conc. In response to changes in PCO 2 in lungs and tissues. The kidneys play the major role in maintaining the circulating bicarbonate conc. And in elimination H + from the body.

23. The carbonate dehydratase system Bicarbonate is produced following the dissociation of carbonic acid formed from CO 2 and H 2 O. This is catalyzed by carbonate dehydratase (CD) present in high conc. in erythrocytes and renal tubular cells. CO 2 + H 2 O H 2 CO 3 H + + HCO 3 - Carbonate dehydratase

24. In addition to content erythrocytes and renal tubular cell to CD they also have means of removing one of the products, H+ thus both reactions continues to the right and HCO3- is formed. one of the reactants, water, is freely available and one of the products, H + is removed.

25. HCO 3 - generation is therefore accelerated if the conc.of CO 2 rises HCO 3 - falls. H + falls because it is either buffered by erythrocytes or excreted from the body by renal tubular cells. Therefore an increase of intracellular P CO 2 or decrease in intracellular [HCO 3 - ] in the erythrocytes and renal tubular cells maintain the extracellular bicarbonate conc. by accelerating the production of HCO 3 - . This minimizes changes in the ratio of [HCO 3 - ] to PCO 2 and therefore change in PH.

26. In normal subject, at a plasma ; PCO 2 of 40mm of hg (a CO 2 of about 1.2 mmol \L) Erythrocytes and renal tubular cells keep the extracellular bicarbonate at about 25 mmol \L The extracellular ratio of [HCO 3 - ] to [CO 2 ] (both in mmol \L) is just over 20:1.

27. Bicarbonate Generation by the Erythrocytes Erythrocytes produce little CO 2 as they lack aerobic pathway Plasma CO 2 diffuses along a concentration gradient into erythrocytes, where carbonate dehydratase catalyses its reaction with water to from carbonic acid (H 2 CO 3 ) which then dissociates Much of the H + is buffered by hemoglobin and the HCO 3 - diffuses out into the extracellular fluid along a conc. Gradient

28. CARBON DIOXIDE DIFFUSION 28 CO 2 Red Blood Cell Systemic Circulation H 2 O H + HCO 3 - carbonic anhydrase Plasma CO 2 CO 2 CO 2 CO 2 CO 2 CO 2 CO 2 Click for Carbon Dioxide diffusion + + Tissues H + Cl - Hb H + is buffered by Hemoglobin

29. The kidneys Two renal mechanism control [HCO 3 - ]in the extracellular fluid: Bicarbonate reclamation ( reabsorption ) The CO 2 driving in renal tubular cells is derived from filtered bicarbonate, after action of the carbonate dehydratase . There is no correct to an acidosis but can maintain a steady state.

30. Normal urine is nearly HCO 3 - free. An amount equivalent to that filtered by the glomeruli is returned to the body by the tubular cells. The luminal surface of renal tubular cells are impermeable to HCO 3 - . Thus, HCO 3 - can only be returned to the body if first converted to CO 2 in the tubular Lumina, and an equivalent amount of CO 2 is converted to HCO 3 - with in tubular cells.

31. The luminal surface of renal tubular cells are impermeable to HCO 3 - , Thus, HCO 3 - can only be returned to the body if first converted to CO 2 in the tubular Lumina, and an equivalent amount of CO 2 is converted to HCO 3 - with in tubular cells.

32. 32 Capillary Distal Tubule Cells Tubular Urine NH 3 Na + Cl - + H 2 CO 3 HCO 3 - + NaCl NaHCO 3 Click Mouse to Start Animation NaHCO 3 NH 3 Cl - H + NH 4 Cl Click Mouse to See Animation Again Notice the H + - Na + exchange to maintain electrical neutrality

33. Bicarbonate generation A very important mechanism for correcting acidosis, in which the levels of CO 2 or [HCO 3 - ] affecting the carbonate dehydratase reaction in tubular cells reflect those in the extracellular fluid, there is a net loss of H +

34. PHOSPHATE BUFFER SYSTEM 34 1) Phosphate buffer system Na 2 HPO 4 + H + NaH 2 PO 4 + Na + Most important in the intracellular system Alternately switches Na + with H + H + Na 2 HPO 4 + NaH 2 PO 4 Click to animate Na + +

35. PHOSPHATE BUFFER SYSTEM 35 Na 2 HPO 4 + H + NaH 2 PO 4 + Na + Phosphates are more abundant within the cell and are rivaled as a buffer in the ICF by even more abundant protein Na 2 HPO 4 Na 2 HPO 4 Na 2 HPO 4

36. PHOSPHATE BUFFER SYSTEM 36 Regulates pH within the cells and the urine Phosphate concentrations are higher intracellularly and within the kidney tubules Too low of a concentration in extracellular fluid to have much importance as an ECF buffer system HPO 4 -2

37. PROTEIN BUFFER SYSTEM 37 Behaves as a buffer in both plasma and cells Hemoglobin is by far the most important protein buffer. Most important intracellular buffer ( ICF ) The most plentiful buffer of the body Proteins are excellent buffers because they contain both acid and base groups that can give up or take up H + Proteins are extremely abundant in the cell The more limited number of proteins in the plasma reinforce the bicarbonate system in the ECF

38. 38 Hemoglobin buffers H + from metabolically produced CO 2 in the plasma only As hemoglobin releases O 2 it gains a great affinity for H + Hb O 2 O 2 O 2 O 2 H +

39. 39 H + generated at the tissue level from the dissociation of H 2 CO 3 produced by the addition of CO 2 Bound H + to Hb (Hemoglobin) does not contribute to the acidity of blood Hb O 2 O 2 O 2 O 2 H +

40. 40 As H + Hb picks up O 2 from the lungs the Hb which has a higher affinity for O 2 releases H + and picks up O 2 Liberated H + from H 2 O combines with HCO 3 - HCO 3 - H 2 CO 3 CO 2 (exhaled) Hb O 2 O 2 O 2 H + O 2

41. 41 Venous blood is only slightly more acidic than arterial blood because of the tremendous buffering capacity of Hb Even in spite of the large volume of H + generating CO 2 carried in venous blood

42. 42 Proteins can act as a buffer for both acids and bases Protein buffer system works instantaneously making it the most powerful in the body 75% of the body’s buffer capacity is controlled by protein Bicarbonate and phosphate buffer systems require several hours to be effective

43. PROTEIN BUFFER SYSTEM 43 Proteins are very large, complex molecules in comparison to the size and complexities of acids or bases Proteins are surrounded by a multitude of negative charges on the outside and numerous positive charges in the crevices of the molecule - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + + + + + + + + + +

44. PROTEIN BUFFER SYSTEM 44 H + ions are attracted to and held from chemical interaction by the negative charges - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + + + + + + + + + + H + H + H + H + H + H + H + H + H + H + H + H + H + H + H + H + H + H + H + H + H +

45. PROTEIN BUFFER SYSTEM 45 OH - ions which are the basis of alkalosis are attracted by the positive charges in the crevices of the protein - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + + + + + + + + + + OH - OH - OH - OH - OH - OH - OH - OH - OH - OH - OH - OH -

46. PROTEIN BUFFER SYSTEM 46 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + + + + + + + + + + OH - OH - OH - OH - OH - OH - OH - OH - OH - OH - OH - OH - H + H + H + H + H + H + H + H + H + H + H + H + H + H + H + H + H + H + H + H + H +