Acid base homeosatsis

Brief summary on acid base Homeostasis

1. ACID BASE HOMEOSTASIS R.Madhuri Roll no: 5 PHARM-D 4 th YEAR

2. INTRODUCTION : The kidney plays a central role in the regulation of acid–base homeostasis through Excretion or re-absorption of filtered bicarbonate Excretion of metabolic fixed acids Generation of new bicarbonate The lungs control arterial carbon dioxide levels through changes in the depth and/or rate of respiration 2

3. ACID - BASE CHEMISTRY Acid VOLATILE ACID Base The degree of acidity is expressed as pH pH = log 1/[H + ] = -log [H + ] Alterations in blood pH serve as the basis for the diagnosis of acid–base disorders 3 FIXED ACID Henderson- Hasselbalch equation: pH = p K + log([base]/[acid])

4. Regulation of acid base homeostasis Buffers function almost instantaneously (rapid) Respiratory mechanisms take several minutes to hours Renal mechanisms may take several hours to days 4

5. EXTRACELLULAR BUFFERING First line of defense Two most common chemical buffer groups 5 Bicarbonate Non bicarbonate (Hb,protein,phosphate) Act instantaneously Regulate pH by binding (Or) releasing H⁺

6. 6 Carbonic acid- bicarbonate buffer system: The bicarbonate buffer is the most important of the body’s buffers, because There is more bicarbonate present in the extracellular fluid (ECF) than any other buffer component The supply of carbon dioxide is unlimited The acidity of ECF can be regulated by controlling either the bicarbonate concentration or the Pco2. The bicarbonate buffer system easily adapts to changes in acid–base status by alterations in ventilatory elimination of acid (Pco2) and/or renal elimination of base (Hco3–)

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8. Protein Buffer System Plasma and intracellular proteins are the body’s most plentiful and powerful buffers Is the only intracellular buffer system with an immediate effect on ECF pH Helps prevent major changes in pH when plasma Pco2 is rising or falling The charged side chains of amino acids provide the buffering action Carboxyl group gives up H+ Amino Group accepts H+ 8

9. 9 Hydrogen ions are buffered by hemoglobin molecules

10. Phosphate Buffer System The components are Dihydrogen phosphate (H 2 PO 4 - ) Monohydrogen phosphate (HPO 4 -2 ) ions . (H 2 PO 4 - ) acts as weak acid and is capable of buffering strong bases such as OH- as follows: OH - + H 2 PO 4 - → H 2 O + HPO 4 -2 (HPO 4 -2 ) acts as weak base and buffers strong acids such as H+ as follows: H + + HPO 4 -2 → H 2 PO 4 - Phosphates are major anions in intracellular fluid , hence it is an important regulator of pH in cytosol . Extracellular phosphate is present only in low concentrations, so its usefulness as a buffer is limited As an intracellular buffer, phsosphate is more useful. Calcium phosphate in bone is relatively inaccessible as a buffer, but prolonged metabolic acidosis will result in the release of phosphate from bone. 10

11. pH rises to normal CO2 eliminated in lungs Control center : Inspiratory area in medulla oblongata Receptors: central chemo-receptors in medulla oblongata , peripheral chemo receptors in aortic and carotid bodies. Blood pH decreases (increase in H+ concentration) Some stimulus disrupts homeostasis Effector : Diaphragm contracts more forcefully and frequently so more co2 is exhaled RESPIRATORY REGULATION 11

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14. RENAL REGULATION Acid base regulation by Reabsorption of HCO 3 – Secretion of H+ Generation of new HCO 3 – The bicarbonate load delivered to the nephron is approximately 4,500 mEq /day. Bicarbonate reabsorption (>85%) occurs primarily in the proximal tubule. Excretion of metabolic fixed acids and generation of new HCO3– is achieved through renal ammoniagenesis and distal tubular hydrogen ion secretion. Ammoniagenesis plays a critical role in acid–base homeostasis, with ammonium (NH+4) excretion comprising approximately 50% of renal net acid excretion. Distal tubular hydrogen ion secretion accounts for the remaining 50% of net acid excretion. 14

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18. Acid-base disturbances Alterations in blood pH are designated by the suffix “- emia ” Acidemia is an arterial blood pH <7.35 Alkalemia is an arterial blood pH >7.45 The pathophysiologic processes that result in alterations in blood pH are designated by the suffix “- osis .” These disturbances are classified as either Metabolic Respiratory 18

19. 19 PATHOPHYSIOLOGY Changes in the arterial pH are driven by changes in PaCO2 and/or serum HCO3– Carbon dioxide is a volatile acid that is under respiratory control A respiratory acid-base disorder is a pH disturbance caused by pathologic alterations of the respiratory system or its central nervous system control. PaCO2 (greater than 45 mm Hg), Respiratory acidosis (less than 35 mm Hg), Respiratory alkalosis Variations in respiratory rate and/or depth allow the lungs to achieve changes in the PaCO2 very quickly (within minutes).

20. 20 Bicarbonate is a base that is regulated by renal metabolism via the enzyme carbonic anhydrase . It is under metabolic control. A metabolic acid-base disorder is a pH disturbance caused by derangement of the pathways responsible for maintaining a normal HCO3– level. HCO3– (greater than 26 mEq /L ) Metabolic alkalosis (less than 22 mEq /L) Metabolic acidosis. In contrast to the lungs rapid effects on CO2, the kidneys change the HCO3– very slowly (hours to days).

21. 21 COMBINATION Respiratory and metabolic derangements can occur in isolation or in combination The most common clinical disturbances are simple acid-base disorders. If two or three simple acid-base disorders are simultaneously present the patient has a mixed (complicated) disorder. If a respiratory acid-base disturbance is present for Minutes to hours - Acute disorder Days or longer - Chronic disorder The metabolic machinery that regulates HCO3– results in slow changes in serum bicarbonate and all metabolic disorders are chronic

22. 22 COMPENSATION Because all metabolic acid-base disorders are chronic and the normal respiratory system can quickly alter the PaCO2, Essentially all metabolic disorders are accompanied by some degree of respiratory compensation Chronic respiratory acid-base disorders are typically accompanied by attempts at metabolic compensation With acute respiratory acid-base disorders there is insufficient time for the metabolic pathways to compensate significantly.

23. 23 Acid–Base Disorder pH Primary Disturbance Compensation Acidosis Respiratory Decrease Increase PaCO2 Increase HCO3– Metabolic Decrease Decrease HCO3– Decrease PaCO2 Alkalosis Respiratory Increase Decrease PaCO2 Decrease HCO3– Metabolic Increase Increase HCO3– Increase PaCO2

24. 24 Acid-base nomogram

25. Clinical assessment of acid-base status Arterial blood reflects how well the blood is being oxygenated by the lungs (an accurate measurement of PaO2) whereas venous blood reflects how much oxygen tissues are using. Arterial blood rather than venous blood should be used whenever possible because venous blood obtained from an extremity can provide misleading information Partial pressure of oxygen from arterial blood [PaO2] Partial pressure of oxygen from venous blood [PvO2 ]. Arterial Blood Mixed Venous Blood pH 7.40 (7.35–7.45) 7.38 (7.33–7.43) PO 2 80–100 mm Hg 35–40 mm Hg SaO 2 95% 70%–75% PCO 2 35–45 mm Hg 45–51 mm Hg HCO 3 – 22–26 mEq /L ( mmol /L) 24–28 mEq /L ( mmol /L) 25

26. ANALYSIS OF BLOOD GAS DATA Arterial blood gases provide an assessment of the patient’s acid–base status. The bicarbonate calculated from the patient’s PaCO2 and pH of the blood gas should be compared with the measured total CO2 content Ordinarily, the blood gas bicarbonate value(24mEq/L) is approximately 1 to 2 mEq /L less than total CO2 content (26 to 30 mmol /L). 26

27.     pH  < 7.35   7.35 - 7.45  > 7.45  Acidosis  Normal or Compensated  Alkalosis INTERPRETATION Step:1 use pH to determine acidosis or alkalosis Step 2: use paCO₂ to determine respiratory effect    PaCO2   < 35  35 -45 > 45  Tends toward alkalosis Causes high pH  Normal or Compensated  Tends toward acidosis Causes low pH 27

28. Step:3 Assume metabolic cause if respiratory is ruled out :  High pH Low pH  Alkalosis Acidosis  High PaCO2 Low PaCO2 High PaCO2 Low PaCO2  Metabolic Respiratory Respiratory Metabolic If PaCO2 is abnormal and pH is normal, it indicates compensation. pH > 7.4 would be a compensated alkalosis pH < 7.4 would be a compensated acidosis Step4: use HCO₃ to verify metabolic effect Normal range:22 to 26 High PaCO2 and low HCO3- (acidosis) or Low PaCO2 and high HCO3- (alkalosis) 28

29. ANION GAP CONCEPT (SAG) To know if Metabolic Acidosis due to Loss of bicarbonate Accumulation of non-volatile acids Provides an index of the relative conc. of plasma anions other than chloride, bicarbonate SAG= [ Na⁺] – ( [ Cl ⁻] + [HCO₃⁻]) To maintain electroneutrality , the total concentration of cations in the serum must be equal to the total concentration of anions. [Na+] + [UCs] = [ Cl –] + [HCO3–] + [UAs] Therefore the SAG can be expressed as: SAG = [UAs] – [UCs] The normal SAG is approximately 9 mEq /L , with a range of 3 to 11 mEq /L.

30. Metabolic Acidosis Increased AG M.acidosis (or) Normochloremic M.acidosis Normal AG M.acidosis (or) Hyperchloremic M.acidosis net gain of acid loss of bicarbonate

31. ADJUSTED ANION GAP Hypoalbuminemia can mask an increased concentration of gap ions, lowering the value of AG Adjusted AG = AG + 2.5[ normal albumin ( g/ dL ) - obtained albumin (g/ dL )] DELTA RATIO / GAP-GAP Ratio between change(↑)in AG and change(↓)in bicarbonate AG BICARBONATE HAGMA(NORMOCHLOREMIC ACIDOSIS) :- RATIO = 1 HYPERCHLOREMIC ACIDOSIS (NAGMA):- RATIO < 1 In DKA after therapy with NS Met.acidosis with Met.alkalosis :- RATIO > 1

32. Steps in Acid–Base Diagnosis Obtain arterial blood gases (ABGs) and electrolytes simultaneously. 2. Compare [HCO3 –] on ABG and electrolytes to verify accuracy. 3. Calculate anion gap (AG). 4. Is acidemia (pH <7.35) or alkalemia (pH >7.45) present? 5. Is the primary abnormality respiratory (alteration in PaCO2) or metabolic (alteration in HCO3)? 6. Estimate compensatory response 7. Compare change in [ Cl –] with change in [Na+] 33

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34. CASE 58 y.o . female with weakness and muscle aches 139 115 3.1 17 7.34 / 87 / 33 / 17

35. 36 pH / pO2 / pCO 2 / HCO 3 Acidosis / alkalosis As the pH is less than 7.35 it is acidosis Determine if it is respiratory or metabolic The pH, bicarbonate and pCO 2 all move in the same direction (up ) It is metabolic P rimary disorder Metabolic Acidosis 7.34 ↓ / 87 ↓ / 33 ↓ / 17 ↓

36. 37 Predicting pCO 2 in metabolic acidosis: Winter’s Formula In metabolic acidosis the expected pCO 2 can be estimated from the HCO3- Expected pCO 2 = (1.5 x HCO 3 ) + 8 ± 2 If the pCO 2 is higher than predicted then there is an addition respiratory acidosis If the pCO 2 is lower than predicted there is an additional respiratory alkalosis Expected pCO 2 = (1.5 x HCO 3 ) + 8 ±2 = (1.5 x 17)+ 8 ± 2 = 31.5 to 35.5 Actual pCO 2 is 33, which is within the predicted range, indicating a simple metabolic acidosis

37. 38 Appropriately compensated metabolic acidosis Metabolic acidosis is further evaluated by determining the anion associated with the increased H+ cation It is either chloride(Non-Anion Gap Metabolic Acidosis) (Or) it is not chloride(Anion Gap Metabolic Acidosis) These can be differentiated by measuring the anion gap =

38. 39 Calculating the anion gap 139 115 3.1 17 Anion gap = Na – (HCO 3 + Cl ) Anion gap = 139 – (17 + 115) Anion gap = 7 FINAL DIAGNOSIS: Appropriately compensated non-anion gap metabolic acidosis Normal anion gap is 6 ±3

39. 40 CONCLUSION All acid-base abnormalities result from underlying disease processes. Definitive therapy for these disturbances requires treatment of the illness that has disrupted the pH equilibrium Serial arterial blood gases and serum chemistries should be compared, as every patient’s acid-base status can be continuously changing based on the underlying disease state and any therapy initiated…

40. 41 REFERENCE JOSEPH T. DIPIRO Pharmacotherapy, A pathophysiologic approach 8th Edition , pg no:889 MCGRAW-HILL Medical Publishing Division MARIE A. CHISHOLM-BURNS ,BARBARA G.WELLS ,JOSEPH T. DIPIRO Pharmacotherapy principles and practice Page no: 419 MCGRAW-HILL Medical Publishing Division http://www.austincc.edu/apreview/EmphasisItems/Electrolytefluidbalance.html

41. 42 THANK YOU..!!