Acid-base balance (ABB)

Transcription

1 Acid-base balance (ABB)

2 Overview of the lecture ph, relationships between metabolism and changes of ph: Definition of ph, ph values in the different body compartments Production of acids and bases in the metabolism Systems that participate in ABB: Buffer systems The role of lungs, kidneys and liver in the maintenance of the acid base balance Examination of the ABB status Basic ABB disorders and their compensation

3 Internal environment Composition of liquid surrounding cells. Belongs among vital functions. Components: constant volume (izovolumia) constant tonicity (izoosmolarity) and composition (izoionia) constant ph (izohydria)

4 ph = - log [H + ] From year 1909 is the concentration of H+ expressed as ph. This is good form chemists, but really bad for doctors and medical students. Everything would be simplier, if we still can use concentration of H nmol/l. Instead of we have nonlinear ph, where decrease of ph means increase of acidity.

5 Opening ph = - log c H + ph = 7,4 c H + = 40 nm Acid = donor of H + Base = acceptor of H + Buffer is a mixture of compounds which have the ability to absorb small amounts of H + or OH - with very little change of ph. = system maintaining ph Acidosis is a disorder, which leads to decrease in blood ph (< 7.35) Alkalosis is a disorder, which leads to increase in blood ph ( 7.45)

6 Concentration of H + ph = - log [H + ] Normal values ph = 7,40 (7,36-7,44) [H + ] = 40 nmol/l Other ions: [Na + ] = 140 mmol/l [HCO 3- ] = 25 mmol/l

7 Borders of ph Figure is found on

8 Borders of ph Obrázek převzat z (duben 2007)

9 IC and EC ph Neutral ph means the same amount of [H + ] and [OH - ]. Intracelular ph is ~ 7,0. IC [H + ] nmol/l. ph of arterial blood is 7,4. EC [H + ] - 40 nmol/l; H + follow this gradient, when they are leaving cells. Venous blood and interstitial fluid have ph 7.35

10 Acids and bases in body Source of acids: metabolism Source of bases: food Their fate: transformation by the metabolism excretion

11 Where we gain and lose H +? Protonproductive reactions: Anaerobic glykolysis in muscles and ery: Glucose 2 CH 3 CHOH COO H + Ketogenesis: MK ketone bodies + n H + + Lipolisis: TAG 3 FA + glycerol + 3 H Synthesis of urea in liver: CO 2 + 2NH 4 urea + H 2 O + 2H + Protonconsuming reactions: Gluconeogenesis 2 lactate + 2 H + Glc Oxidation of neutral and dicarboxylated AA Protonneutral reactions: Full oxidation of glucose, lipogenesis from Glc

12 ~ mmol / den Obrázek převzat z knihy: J.Koolman, K.H.Röhm / Color Atlas of Biochemistry, 2 nd edition, Thieme 2005

13 The metabolism produces acids Full oxidation: carbon skeleton CO 2 + H 2 O HCO H + CO 2 can be breathed out, problem is, when the lungs aren`t working well Saccharides glucose pyruvate, lactate + H + Triacylglycerols FA, ketone bodies + H + Phospholipids phosphate + H + Proteins amino acids sulfate, urea + H +

14 Acids formed in the body Respiratory (volatile) acids mmol of CO 2 /day excretion by the lungs CO 2 + H 2 O H 2 CO 3 HCO H +

15 Acids formed in the body Metabolic (nonvolatile) acids 1mmol/kg/day excreted by kidneys, or metabolized a) organic acids: are continually produced as a by-product of metabolism glucose lactic acid lactate + H + TAG 3 RCOO - + 3H + + glycerol (Lipolysis) FA ketone bodies: acetoacetic a. acetoacetate + H + β-hydroxybutyric a. β-hydroxybutyrate + H + Under normal conditions are these acids completely metabolized to CO 2 and H 2 O. They have no effect on ABB b) inorganic acids: excretion by kidneys amino acids Cys and Met H 2 SO 4 sulfate + 2H + 2- Phospholipids, NA H 3 PO 4 HPO 4 + 2H +

16 Synthesis of ATP is connected with the production of H + Human body is well equipped to cope with acids

17 The order of systems that participate in ABB Buffers (changes of ph caused by common metabolism) react in seconds. The lungs (CO 2 ) - Respiratory centre in brain stem reacts in 1 3 min. The kidneys (H +, HCO 3- ) - Need hours, days. Blood ph can be also affected by: The liver (synthesis of urea / glutamine from the ammonia, metabolism of lactate) The heart (oxidation of ketone bodies and lactate)

18 Body maintains physiologic ECF ph by buffer systems One or two molecules that act to resist ph changes when strong acid or base is added Blood buffers are: Bicarbonate buffer (HCO 3 - / CO 2 ) - 53% Hemoglobin in ery - 35% Plasma proteins (mainly albumin) - 7% Phosphate buffer (HPO 4 2- / H 2 PO 4- ) - 3% Any drifts in ph are resisted by the entire chemical buffering system.

19 Henderson - Hasselbach equation ph of the buffer depends on the logarithm of the ratio base/acid. For given ph we gain specific ratio of these components. [A - ] ph = pk a + log [HA]

20 Principle of Isohydria The ratio of acid and base in each buffer depends only on ph and buffer pair pk a. Buffers work best at ph = pk ± 1 All body buffers are in equilibrium. Changing the concentration of any member of any buffer couple is reflected in the ph and thus in all body buffers.

21 Principal buffer systems fluid buffer note ISF bicarbonate buffers metabolic acids phosphate proteins low concentration low concentration blood bicarbonate buffers metabolic acids hemoglobin buffers CO 2 (H 2 CO 3 ) plasma proteins phosphate low concentration low concentration ICF proteins important buffer phosphate important buffer urine phosphate related to almost all titratable acidity of the urine ammonium important: excretion of both NH 3 and H + ; cation!!!

22 Blood buffers - overview bicarbonate buffer: HCO 3- /CO 2 pk(h 2 CO 3 ) = 6,1 phosphate buffer: HPO 4 2- /H 2 PO 4 - pk(h 2 PO 4- ) 7,0 hemoglobin: Hb - /Hb-H + pk(hhbo 2 ) = 6,17 pk(hhb) = 7,82 proteins: protein/protein-h + 24 mm 1 mm 160g/L 70g/L pk = 4 12 (mainly Asp, Glu and His)

23 Blood buffers pufr plasma erythrocytes sum HCO 3- /CO 2 35 % 18 % 53 % Hb/Hb-H % 35 % plasma proteins 7 % - 7 % inorganic phosphate 1 % 1 % 2 % organic phosphate - 3 % 3 % 43 % 57 % 100 %

24 Bicarbonate Buffer System Is the most important EC buffer. Its importance is so great, because the body can actively change the concentration of HCO 3 - and pco 2 : [CO 2 ] / pco 2 is changed by ventilation [HCO 3 ] is changed by kidneys and liver Bicarbonate buffer is an open buffer system The effectiveness of buffer is much greater than would be expected from the pk = 6.1 Using the values of bicarbonate buffer can doctors assesses the state of ABB in the patients (ph, [HCO 3 - ] and pco 2 ).

25 HCO 3- /CO 2 system is an open buffer system CO 2 elimination (pco 2 ) is controlled by lungs (respiratory system). It takes 1 3 min to respond to changes in ph and effect changes in the ph. ventilation pco 2 alkalinization ventilation pco 2 acidification HCO 3 - elimination / synthesis is controlled by kidneys. Urinary system needs several hours or days to compensate changes in ph.

26 Protein Buffer System Plasma and intracellular proteins are the body s most plentiful and powerful body buffers. Some amino acids of proteins have: Free organic acid groups (weak acids) Groups that act as weak bases (e.g. amino groups) Hb is the most important - 35% of the buffering capacity of the blood, the other proteins only 7% of the buffering capacity of the blood.

27 Hemoglobin as a Buffer In the working tissue absorbs protons and helps the body to cope with the acid load (production of HCO 3 - ). On the other hand, in the lungs are H + released. They combine with HCO 3 - to produce CO 2. Exchange of HCO 3 - for Cl - in the erythrocyte membrane is called the Hamburger's effect. This process proceeds also in gastric parietal cells (the formation of HCl) and in the kidney tubules (the resorption of HCO 3 - ).

28 Hemoglobin as a Buffer In the tissue Hb releases O 2 and binds H + H + is produced: CO 2 + H 2 O HCO H + Bicarbonate is transported from the ery in exchange for Cl -. In the lungs Hb binds O 2 and releases H + H + reacts with HCO 3 - : HCO H + CO 2 + H 2 O CO 2 is breathed out, bicarbonate is replenished from plasma (exchange for Cl -.

29 Hb as a O 2 Buffer O 2 (March 07)

30 Phosphate Buffer System Nearly identical to the bicarbonate system. Its components are: Inorganic phosphate: Sodium salts of dihydrogen phosphate (H 2 PO 4- ), a weak acid Monohydrogen phosphate (HPO 4 2- ), a weak base - H 2 PO 4 + H 2 O HPO4-2 + H 3 O + But also organic compounds (AMP, ADP, ATP) This system is an effective urine and IC buffer.

31 Urine buffers 1 excreted H + 1 reabsorbed HCO 3 - NH 3 + H + NH mmol H + /day H + + HPO 4 2- H 2 PO 4-20 mmol H + /day NH 3 /NH 4 + and HPO 4 2- /H 2 PO 4 - are the most important urinary buffer systems. About 50 mmol of NH 4 + is excreted in the daily urine, but the excretion is controlled during acid-base disorders. Urine ph varies between

32 The kidney (and lung) is the most important organ for maintaining acid-base balance. Protecting the internal environment against acid overload.

33 Role of lungs in the ABB Excrete about 15 moles of CO 2 a day. pco 2 in the venous blood is about 6,13 kpa (46 mmhg). Due to good CO 2 solubility are its concentrations in the alveoli and in the arterial blood equal - pco 2 in the arterial blood is 5,33 kpa (40 mmhg). pco 2 depends on the minute ventilation - the number of breaths x tidal volume. The increase in the pco 2 leads to decrease in ph, pco 2 decrease means an increase in ph.

34 Renal Mechanisms of ABB Chemical buffers can tie up excess of acids or bases, but they cannot eliminate them from the body. The lungs can eliminate carbonic acid by eliminating carbon dioxide. Only the kidneys can rid the body of metabolic acids (phosphoric, uric and lactic acids and ketones) and can resist the metabolic acidosis. Moreover, only the kidney is able to effectively deal with alkalosis (otherwise we could only stop breathing). The ultimate acid-base regulatory organ are the kidneys.

35 Renal Mechanisms of ABB The most important renal mechanisms for regulating acid-base balance are: Conserving (reabsorbing) or generating new bicarbonate ions. Excreting bicarbonate ions. Losing a bicarbonate ion is the same as gaining a hydrogen ion; reabsorbing a bicarbonate ion is the same as losing a hydrogen ion.

36 Renal Mechanisms of ABB Hydrogen ion secretion occurs in the PCT (Proximal convoluted tubule) and in type A intercalated cells (DCT and collecting duct). Hydrogen ions come from the dissociation of carbonic acid. Bicarbonate secretion takes place in type B intercalated cells.

37 Reabsorption of bicarbonate Na + /H + exchanger (April 2007)

38 Reabsorption of bicarbonate Bicarbonate is in PCT in urine. Hydrogen ions are secreted to urine in PCT and form together with bicarbonate carbonic acid. Carbonic acid splits into carbon dioxide and water. These nonpolar compounds can go freely through membranes of tubular cells. In cells you do the oposite reactions and then transport reabsorbed bicarbonate to blood. For each hydrogen ion secreted, a sodium ion and a bicarbonate ion are reabsorbed by the PCT cells. Thus, bicarbonate disappears from filtrate at the same rate that it enters the peritubular capillary blood.

39 Reabsorption of bicarbonate Carbonic acid formed in filtrate dissociates to release carbon dioxide and water Carbon dioxide then diffuses into tubule cells, where it acts to trigger further hydrogen ion secretion

40 Generating of the new bicarbonate Generating of the new bicarbonate takes place in the type A intercalated cells. H + is secreted by the proton pump direct ATP demand active transport. Main urine buffers are ammonia and phosphates.

41 Hydrogen Ion Excretion Dietary hydrogen ions must be counteracted by generating new bicarbonate. H + secretion into the distal tubule: Intercalated cells A actively secrete hydrogen ions into urine, which is buffered and excreted. H + ATPase performs H + transport. Aldosteron increases H + secretion. Hydrogen ion in the urine reacts with NH 3 (glutaminase, GDH) or HPO 4 2- Urine ph varies between Generated bicarbonate goes into peritubular capillary blood via a cotransport system.

42 Hydrogen Ion Excretion In response to acidosis: Kidneys generate bicarbonate ions and add them to the blood An equal amount of hydrogen ions are added to the urine

43 Generating of the new bicarbonate (April 2007)

44 Generating of the new bicarbonate (April 2007)

45 Ammonium Ion Excretion This process uses ammonia that is produced by the metabolism of glutamine in tubular cells. Glutamine's metabolism produces two ammonium ions and two bicarbonate ions. Bicarbonate moves to the blood and ammonium ions are excreted in urine.

46 Bicarbonate Ion Secretion When the body is in alkalosis, type B intercalated cells: Do the bicarbonate ion secretion Reclaim hydrogen ions and acidify the blood The processes in type A and type B intercalated cells are opposite (secretion in type B x resorption in type A). Even during alkalosis, the nephrons excrete fewer bicarbonate ions than they conserve.

47 The liver detoxication of ammonia according to the ABB state amino acids LIVER, MUSCLE carbon skeleton LIVER favourized during alkalemia urine urine favourized during acidemia The figure has been adopted from: Klinická biochemie. Požadování a hodnocení biochemických vyšetření. Karolinum, Praha, ISBN CO NH 4 urea + 2 H + + H 2 O NH Glu Gln + H 2 O

48 Glutamine cycle in the liver The figure has been adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley Liss, Inc., New York, ISBN

49 Summary ph of extracellular fluid is maintained by buffer systems in the range: 7.36 to ph is determined by the ratio pco / [HCO ] by the H.-H equation. pco is changed by lungs and 2 [HCO - ] by kidneys. 3

50 Physiological values of ABB (Astrup investigation) ph 7,36-7,44 po 2 pco 2 - HCO 3 BE 9,9-13,3 kpa mmhg 4,80-5,90 kpa mmhg 24 ± 2 mm 0 ± 2,5 mm BE (base excess) is defined as the amount of the strong acid that must be added to the liter of blood to return the ph to 7.40 at a temperature of 37 C and a pco 2 of 5.3 kpa.

51 Ions ECT Changes in ABB influence all ions, but mostly kalemia. Anion gap

52 Anion gap (AG) The sum of the concentrations of Na + and K + is greater than the sum of concentrations of HCO 3 - and Cl -. Difference is called anion gap. AG is calculated: AG = (Na + + K + ) (HCO Cl - ) Normal values of AG: mmol/l AG represents the plasma anions which are not routinely measured (albumin, phosphates, sulphates, organic anions, some toxic compounds). If there are new acids in blood, their anions replace the existing anions and the anion gap increases. AG is therefore calculated in the case of metabolic acidosis.

53 Anion Gap METABOLIC ACIDOSIS NORMAL Hyperchloremic High Anion Gap AG HCO 3 - AG HCO 3 - AG HCO 3 - Na + Na + Na + Cl - Cl - Cl -

54 BE - Base excess BE is defined as the amount of moles of the strong acid that must be added to liter of fully oxygenated blood to return the ph to 7.40 at a temperature of 37 C and a pco 2 of 40 mmhg (5.3 kpa). Optimal for the evaluation of metabolic component of ABB. Normal: 0 ± 2,5 mm A negative value indicates an excess of acids - metabolic acidosis. A positive value indicates an excess of bases - a metabolic alkalosis.

55 Kalemia 3,8-5,3 mm Acidosis release of K + from cells hyperkalemia loss of K + with urine (quick alkalization of the organism by treatment can cause consequent hypokalemia danger of heart beat imbalance) Alkalosis K + replaces H + in cells decrease of K + in blood hypokalemia; K + is excreated into urine instead of H + (exchange with Na + )

56 Basic ABB disorders Acidosis: a process leading to a decrease in blood ph. Alkalosis: the process leading to a rise in blood ph.! CAVE! All calculations in the ABB are calculated in human plasma, its ph is in the alkaline range ~ 7.4 (H + concentration ~ 40 nmol/l). Respiratory disorders = caused by changing pco 2 Metabolic disorders = caused by changing [HCO 3 - ].

57 Basic ABB disorders Respiratory acidosis: decrease in blood ph, caused by increased pco 2 Respiratory alkalosis: increase in blood ph, caused by decreased pco 2 Metabolic acidosis: decrease in blood ph, caused by decreased [HCO 3 - ] Metabolic alkalosis: increase in blood ph, caused by increased [HCO 3 - ]

58 ABB disorders The figure has been adopted from J.Koolman, K.H.Röhm / Color Atlas of Biochemistry, 2 nd edition, Thieme 2005

59 ABB disorders Primary process Compensation metabolic acidosis [HCO 3 ] pco 2 metabolic alkalosis [HCO 3 ] pco 2 respiratory acidosis pco 2 [HCO 3 ] respiratory alkalosis pco 2 [HCO 3 ]

60 Compensation Effort to readjust plasma ph back toward normal. Acid-base imbalance due to inadequacy of a one system is compensated by the other system. respiratory disorders are compensated by the kidneys (3-5 days) metabolic disorders are compensated by the lungs (12-24 hours) or corrected by the kidneys

61 Respiratory Compensation The respiratory system will attempt to correct metabolic acid-base imbalances. In metabolic acidosis: The rate and depth of breathing are elevated. Blood ph is below 7.35 and bicarbonate level is low. As CO 2 is eliminated by the respiratory system, pco 2 falls below normal. In metabolic alkalosis: Compensation exhibits slow, shallow breathing, allowing CO 2 to accumulate in the blood.

62 Renal Compensation To correct respiratory acid-base imbalance, renal mechanisms are stepped up. RAc has high pco 2 and high bicarbonate levels. The high pco 2 is the cause of acidosis. The high bicarbonate levels indicate the kidneys are retaining bicarbonate to cope with the acidosis. RAl has low pco 2 and high ph The kidneys eliminate bicarbonate from the body by failing to reclaim it or by actively secreting it.

63 Physiological values of ABB (Astrup investigation) ph 7,36-7,44 po 2 pco 2 - HCO 3 BE 9,9-13,3 kpa mmhg 4,80-5,90 kpa mmhg 24 ± 2 mm 0 ± 2,5 mm BE (base excess) is defined as the amount of the strong acid that must be added to the liter of blood to return the ph to 7.40 at a temperature of 37 C and a pco 2 of 5.3 kpa.

64 Respiratory acidosis and alkalosis Result from failure of the respiratory system to balance ph. pco 2 is the single most important indicator of respiratory inadequacy. pco 2 levels: Normal pco 2 fluctuates between 35 and 45 mmhg. Values above 45 mm Hg signal respiratory acidosis. Values below 35 mm Hg indicate respiratory alkalosis.

65 Respiratory acidosis (RAc) RAc is the most common cause of acid-base imbalance. Occurs when a person breathes shallowly, or gas exchange is hampered by diseases such as pneumonia, cystic fibrosis, or emphysema. RAc is caused by hypoventilation. Hypoventilation is associated with an impaired ability to eliminate CO 2, therefore the pco 2 increases and the accumulated CO 2 reduces the arterial ph. Other causes: airway obstruction, neuromuscular disorders, disorders of CNS, opiate poisoning - Compensation: reabsorption of HCO 3 in kidneys

66 Respiratory alkalosis (RAl) Respiratory alkalosis is a common result of hyperventilation. The hyperventilation is disproportionately high compared to the CO 2 production, whereby the pco 2 falls and the ph increases. Causes: CNS injury, salicylate poisoning, fever, Other typical cases are the anxious patient during an attack of asthma or the hysterical hyperventilation in neurotic patients. - Compensation: renal excretion of HCO 3 plasma ph decreases toward normal ph.

67 Metabolic acidosis and alkalosis All ph imbalances except those caused by abnormal blood carbon dioxide levels. BE is optimal for the evaluation of metabolic component of ABB. Normal BE: 0 ± 2,5 mm A negative value indicates an excess of acids - metabolic acidosis. A positive value indicates an excess of bases - a metabolic alkalosis.

68 Metabolic acidosis (MAc) MAc is the second most common cause of AB imbalance. MAc is caused by accumulation of acids in ECF or excessive loss of bicarbonate ions. Negative BE. Causes: hypoxia is a lack of O 2 in tissues anaerobic glycolysis produces lactic acid lactate acidosis shock overproduction of ketone bodies ketoacidosis (DM, starvation) ingestion of methanol, ethylene glycol or too much alcohol Diarrhoea, Kidney failure

69 Metabolic acidosis (MAc) Compensation of MAc: 1 st step: buffering of excess of H + by HCO 3-2 nd step: respiratory compensation by hyperventilation 3 rd step: renal correction excretion of H + in urine

70 Metabolic alkalosis (MAl) Rising blood ph and bicarbonate levels indicate metabolic alkalosis. MAl is caused by a primary accumulation of bases in ECF. Both the [HCO 3- ] and the [noncarbonic buffer base] are increased, so the BE is increased. Causes: Intake of excess base (ingestion of alkaline drugs e.g. antacids - NaHCO 3 ) prolonged vomiting the acid contents of the stomach Constipation, in which excessive bicarbonate is reabsorbed

71 Metabolic alkalosis (MAl) Compensation: 1 st step: buffering of excess of HCO 3-2 nd step: respiratory compensation by hypoventilation pco in 2 arterial blood 3 rd step: renal correction: - excretion of HCO 3 in urine