UNIT 9 INVESTIGATION OF ACID-BASE DISTURBANCES

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1 UNIT 9 INVESTIGATION OF ACIDBASE DISTURBANCES LEARNING OBJECTIVES At the end of this chapter, students must be able to: 1. Describe the main parametres that define the acidbase equilibrium 2. Identify the main and secondary (compensatory) modifications that define an acidbase disturbance 3. Establish the level of compensation in a primary acidbase disturbance (non, partially or totally ). 4. Describe the main causes for each acidbase disturbance 5. Diagnose a combined acid base disturbance The acid base balance is defined as the ability to maintain within normal range the ph in the extracellullary fluid, that is between 7,35 7,45. ph = log [H + ] Maintaing a normal ph is possible due to the existence of the following elements: buffer systems (as the first line of defense) the lungs (the second line of defense) the kidney (the third line of defense) A buffer system an association between a light acid and its conjugated base. The main role of such an association is the rapid intervention in order to prevent large variations of blood ph. The main extracellular buffer system is the bicarbonate/carbonic acid HCO 3 / H 2 CO 3, with the following characteristics: 1. It results from the dissociation of H 2 CO 3 in cells that have the enzyme called carbonic anhydrase (e.g. erythrocytes, cells from the renal tubes), cells that have the ability to fixate (e.g. erythrocytes on intracellular buffer systems) or to eliminate (e.g. renal tube cells due to the H + or K + /H + ATPase) protons (H + ) that result from H 2 CO 3 dissociation (H 2 CO 3 HCO 3 + H + ) 2. High concentration in the extracellular fluids ( 24 mmol/l in the plasmatic fluid) 3. Its dissociation constant (pka = 6,1), has a value close to that of the extracellular ph. 4. Its components can easily adjust: HCO 3 due to kidney intervention HCO 3 is the component of the buffer system 5. Rapid intervention in case of a large amount of acid: o HCO 3 + H + H 2 CO 3 o H 2 CO 3 CO 2 + H 2 O The Henderson Hasselbach equation describes the relation between the buffer system parameters that define the acidbase balance: 1. ph = the ph of the solution in which the HCO 3 /H 2 CO 3 buffer system can be found. Normal value: ph = 7,4 2. pka (the dissociation constant) = the ph of the solution that allows the dissociation of aproximately 50% of the H 2 CO 3 into HCO 3 + H + pka = 6,1 3. The bicarbonate concentration [HCO 3 ]: Normal value: [HCO 3 ] = 24 mmol/l 4. The carbonic acid concentration ([H 2 CO 3 ]) depends upon PaCO 2 according to the following relation: [H 2 CO 3 ] = 0,03 x PaCO 2 where: o 0,03 = the solubility constant for CO 2 in H 2 O o PaCO 2 = the partial pressure of CO 2 in the arterial blood Normal value: PaCO 2 = 40 mmhg [H 2 CO 3 ] = 1,2 mmol/l 5. The ratio [HCO 3 ]/[H 2 CO 3 ] or [HCO 3 ]/[0,03 x PaCO 2 ] = the ratio that dictates ph values Normal value is 20 1

2 According to the HendersonHasselbalch equation: [HCO3] ph pka log [H2CO 3] [HCO3] ph pka log [0,03 x PaCO 2] 24 ph 6,1 log 6,1 log 20 6,1 1,30 7,4 1,2 Compensation processes for acidbase disturbances (ABD) The acidbase compensation mechanisms can bring the [HCO 3 ]/[H 2 CO 3 ] ratio to its normal value ( 20), regardless of the values taken by its parameters. The METABOLIC acidbase disturbances are characterised by a PRIMARY modification of bicarbonate HCO 3 which leads to a SECONDARY, compensating modification of carbonic acid H 2 CO 3. The ABD are due to modifications in lung ventilation processes. The compensation process takes place rapidly (minutes), due to carotid and aortic chemoreceptors, which are highly sensitive to ph disturbances : an acid ph ([HCO 3 ] with a [HCO 3 ]/[H 2 CO 3 ] 20) will induce hiperventilation, which leads to: o a compensatory decrease of PaCO 2 and [H 2 CO 3 ] o normalisation of [HCO 3 ]/[H 2 CO 3 ] an alkaline ph ([HCO 3 ] with a [HCO 3 ]/[H 2 CO 3 ] 22) will induce hypoventilation that leads to: o a compensatory increase of PaCO 2 and [H 2 CO 3 ] o normalisation of [HCO 3 ]/[H 2 CO 3 ] The RESPIRATORY acidbase disturbances are characterised by a PRIMARY modification of PaCO 2 and thus, the modification of carbonic acid H 2 CO 3, which will then induce a SECONDARY modification of bicarbonate HCO 3 levels. Respiratory ABD are due to processes controlled by the kidneys. This compensation takes place slowly (1224 hours) and reaches its peak after 35 days. The renal compensating mechanisms are based upon the kidneys ability to modify the reabsorbtion of HCO 3 and H + excretion processes : an acid ph (PaCO 2 [H 2 CO 3 ] with [HCO 3 ]/[H 2 CO 3 ] 20), will lead to: o a compensatory increase in HCO 3 reabsorbtion/production and H + excretion = elimination of acidic urine. o normalisation of the [HCO 3 ]/[H 2 CO 3 ] an alkaline ph (PaCO 2 and [H 2 CO 3 ] and [HCO 3 ]/[H 2 CO 3 ] 22), will lead to: o a compensatory decrease in HCO 3 reabsorbtion/production and H + excretion = elimination of alkaline urine. o normalisation of the [HCO 3 ]/[H 2 CO 3 ] I. INVESTIGATION OF ACIDBASE BALANCE 1. ARTERIAL BLOOD GAS analysis Principle: determination of the ph, PaCO 2 and PaO 2 in the arterial blood with the help of electrodes, followed by automatic determination of the main parameters that define the acidbase balance (Table 1). Table 1. The main parametres obtained thru arterial gas analysis. Parameter Importance N. values ph H + concentration in 7,357,45 the arterial blood PaCO 2 CO 2 amount in the plasma fluid 3545 mmhg Total CO 2 The total CO 2 concentration in the plasma, found as [HCO 3 ] and [H 2 CO 3 ] [HCO 3 ] The plasma HCO 3 concentration: Total CO 2 (0,03 x PaCO 2 ) Base excess (BE) Base excess/defficite in the blood, depending on ph PaCO 2 and Ht levels 2328 mmol/l 2226 mmol/l 03 mmol/l PaO 2 Plasma O 2 levels 80 mmhg SatO 2 (%) O 2 saturated Hb 95% found the plasma 2

3 Keep in mind! BE defines a ABD: positive values define a base excess and nonvolatile acid defficite. negative values define a base defficite and nonvolatile acid excess and are used to aproximate HCO 3 loss in acidoses: HCO 3 loss (mmol/l) = 0,3 x G (kg) x BE In some medical services, the only available method to explore the acidbase balance is the determination of the alkaline reserve. The alkaline reserve the total CO 2 concentration which can be determined in the venous blood thru enzymerelated methods (ECO 2 ) and can be found almost 8090% as HCO 3 : Normal value: 2229 mmol/l Clinical value: lowered AR levels define the, whereas increased AR levels define the this test loses its clinical value in acidbase disturbances (ECO 2 evaluates levels of CO 2 that result from bicarbonate as well as plasma CO 2 ). 2. THE ANIONIC GAP The anionic gap (AG) refers to the plasma anion concentration that participate in maintaining plasma electric neutrality, but ARE NOT determined during usual lab tests. The AG includes: organic anions: ketoacids, lactate anorganic anions: phosphate, sulphate AG (mmol/l) = [Na + ] [(Cl ) + (HCO 3 )] Normal values: 12 4 mmol/l Clinical value: (MA) classification: MA with increased AG in which lowered [HCO 3 ] levels result from using HCO 3 in buffer systems to balance the concentration of H + that results from increased plasma acid dissociation: Increased AG = [Na + ] [Cl + HCO 3 ] MA with normal AG in which lowered [HCO 3 ] levels result from digestive or renal losses of HCO 3, plasma neutrality is maintained because of an increase in chloride renal reabsorbtion: Normal AG = [Na + ] [Cl + [HCO 3 ] III. DIAGNOSIS OF ACIDBASE DISTURBANCES 1. A modified ph suggests the type of acidbase disturbance: Acidosis if the ph is 7,35 Alkalosis if the ph is 7,45 2. If the [HCO 3 ] modifies in the same direction as the ph: The primary modification is a METABOLICAL one and can be: Metabolic primary decrease of [HCO 3 ] 22 mmol/l Metabolic primary increase of [HCO 3 ] 26 mmol/l The secondary/compensatory modification is a RESPIRATORY one; with regards to the degree of compensation, the primary disturbance can be: o De PaCO 2 is normal, but the ph is modified o Partially PaCO 2 modification is the same as HCO 3 modification, but the ph also remains modified o Totally PaCO 2 modification is the same as HCO 3 modification, but the ph values are brought to normal 3. If the [HCO 3 ] modifies in the opposite direction as the ph: The primary modification is a RESPIRATORY one and can be: Respiratory primary increase in PaCO 2 levels 45 mmhg Respiratory primary decrease in PaCO 2 levels 35 mmhg The secondary/compensatory modification is a METABOLICAL one; with regards to the degree of compensation, the primary disturbance can be: o De [HCO 3 ] is normal, but the ph value is modified o Partially [HCO 3 ] modifies in the same sense as PaCO 2, but the ph remains modified. o Totally [HCO 3 ] modifies the same way as PaCO 2, but the phul is restored to its normal value 3

4 4. If PaCO 2 levels and [HCO 3 ] modify in opposite directions and ph levels are highly deviated from normal values The ABD is a MIXT one, due to the association of 2 primary ABD, that are able to modify ph levels in the same way and sense: o Metabolic ([HCO 3 ]) plus Respiratory (PaCO 2 ) can lead to a highly acidic ph MIXT o Metabolic ([HCO 3 ]) plus Respiratory (PaCO 2 ) can lead to a highly alkaline ph MIXT 5. If PaCO 2 levels and [HCO 3 ] are modified in the same sense, but the ph levels are normal The ABD can be: A primary totally ABD (terapeutically) or A mixt ABD that results from the association between two primary ABD the are able to modify the ph values in opposite directions: o Metabolic ([HCO 3 ]) plus Respiratory (PaCO 2 ) o Metabolic ([HCO 3 ]) plus Respiratory (PaCO 2 ) Keep in mind! A totally ABD (ph is restored to its normal value) before any therapeutic measure is applied, is always a mixt ABD. In other words, a total compensation of a primary ABD IS NEVER the proof of pulmonary or renal compensation efficiency, but the consequence of an adequate therapeutical intervention. 1. METABOLIC ACIDOSIS Definition: ph 7,35 primary of [HCO 3 ] 22 mmol/l The degree of compensation is established according to PaCO 2 modifications (Table 2). Table 2. The degree of compensation in a (examples). ph [HCO 3 ] (mmol/l) PaCO 2 (mmhg) Interpretation 7, De 7, Partially 7, Totally Clasification and main causes Metabolic acidoses are classified according to the anionic gap levels : a) Metabolic acidoses with increased AG levels e.g.: Keto: in diabetes mellitus, alchoholism, starvation Lactic : in shock, alchoholism, hepatic failure Toxic acidoses: methanol, ethylenglycol (antifreeze), salicylates (advanced stages) intoxication Renal failure (increases in phosphate and sulphate anion levels) b) Metabolic acidoses with normal AG levelse.g.: Digestive losses of HCO 3 : chronic diarrhea Renal losses of HCO 3 : hypoaldosteronism 2. METABOLIC ALKALOSIS Definition: ph 7,45 primary in [HCO 3 ] 26 mmol/l The degree of compensation is established according to PaCO 2 modifications (Table 3) 4

5 Table 3. The degree of compensation in a ph [HCO 3 ] PaCO 2 Interpretation (mmol/l) (mmhg) 7, De 7, Partially 7, Totally Clasification and main causes Metabolic alkaloses are classified according to their response to 0,9% sodium chloride administration in: a) CHLORIDEsensitive alkaloses (the administration of 0,9% NaCl corrects the ). In terms of water depletion, Na + and Cl, the kidneys are able to compensate by reabsorbing HCO 3, in order to maintain the electroneutrality of the plasma, whilst the administration of 0,9% NaCl will cause a renal elimination of the bicarbonate excess. This type of can be caused by: Digestive losses of water, Na + and Cl due to severe vomiting Renal losses of water, Na + and Cl due to excessive thyaside and loop diuretics administration c) CHLORIDE insensitive alkaloses (0,9% NaCl administration does not correct the ) can be caused by: Excessive HCO 3 intake (antiacid medication) or excessive administration of HCO 3 equivalents (Ringer lactate solution, high amount of cytrate in transfused blood) Increased renal HCO 3 reabsorbtion: hyperaldosteronism 3. RESPIRATORY ACIDOSIS Definition: ph 7,35 primary of PaCO 2 levels 45 mmhg The degree of compensation is established according to bicarbonate changes (Table 4). Table 4. The degree of compensation in a CHRONIC (examples) ph PaCO 2 [HCO 3 ] Interpretation (mmhg) (mmol/l) 7, De 7, Partially 7, Totally Classification and main causes a) Acute is caused by acute hypoventilation, in minutes to hours time and will mostly be de (due to the fact that there is not enough time in order for renal compensation mechanisms to take place). The most frequent causes are: Acute decreases of the centres activity in drug intoxications (e.g. barbiturates) Thoracic lesions due to severe thoracic trauma Paralysis of the muscles in myasthenia gravis Acute airway obstructions due to severe decompensations in asthma, or ingestion of foreign bodies Acute pulmonary edema Chronic is caused by a chronic hypoventilation process and is always followed by maximum renal compensation. The most frequent causes are: COPD Extreme obesity 4. RESPIRATORY ALKALOSIS Definition: ph 7,45 primary in PaCO 2 levels 35 mmhg The degree of compensation is established according to [HCO 3 ] changes (Table 5). 5

6 Table 5. The degree of compensation in a (examples). ph PaCO 2 [HCO 3 ] Interpretation (mmhg) (mmol/l) 7, De 7, Partially 7, Totally c) Classification and main causes Acute is caused by acute hyperventilation, with no posibility of renal compensation. The most frequent causes are: a) Hyperventilation that results from increased centres activity in: panic attacks hyperpyrexia salicylate intoxication (beggining phase) pregnancy (IIIrd trimester) severe pain b) Hyperventilation that results from hypoxia in: pulmonary embolism (beggining phase) moderate decompensations of asthma CHECKPOINT 1. Which of the follwing afirmations regarding ABD is true? A. The ph levels are always above normal B. Can be totally without therapeutical interventions C. Are totally if the ratio between HCO 3 /H 2 CO 3 equals 20 D. Enquire pulmonary compensatory mechanisms in primary disturbances E. Enquire compensatory mechanisms in primary disturbances 2. Which ABD is shown by the following arterial blood gas analysis: ph = 7,55, PaCO 2 = 19 mmhg, HCO 3 = 24 mmol/l? A. De B. Partially C. Partially D. De E. Mixt 3.Which ABD is shown by the following arterial blood gas analysis: ph = 7,55, PaCO 2 = 66 mmhg, HCO 3 = 56 mmol/l? A. De B. Partially C. Partially D. De E. Mixt 4. Which of the following are causes of with increased anionic gap? A. Severe vomiting 6 B. Chronic diarrhea C. Administration of loop diuretics D. Hyperaldosteronism E. Salicylate intoxication 5. Which ABD is shown by the following arterial blood gas analysis in a patient with COPD and vomiting:ph = 7,40, PaCO 2 = 50 mmhg, HCO 3 _ = 30 mmol/l? A. Totally B. Totally C. Partially D. Partially E. Mixt ABD 6. Given the following arterial blood gas analysis, ph = 7,40, PaCO 2 = 33 mmhg, HCO 3 = 20 mmol/l, the mixt ABD enquires: A. Primary B. Compensatory C. Primary D. Primary E. Compensatory 7. Which of the following are true regarding acidbase disturbances? A. Keto leads to with normal anionic gap B. Renal failure leads to C. COPD leads to chronic D. Chronic diarrhea leads to with increased anionic gap E. Severe pain leads to

7 8. A ph level of 7,40: A. Corresponds to a HCO 3 / H 2 CO 3 ratio of 20 B. Corresponds to a HCO 3 / H 2 CO 3 ratio < 18 C. Corresponds to a HCO 3 / H 2 CO 3 ratio > 22 D. Signifies a totally, if PaCO 2 and [HCO 3 ] levels are decreased E. Signifies a totally, if PaCO 2 and [HCO 3 ] levels are increased 9.The following changes can be found in chronic de : A. ph = 7,4 B. ph = 7,28 C. PaCO 2 = 65 mmhg D. [HCO 3 ] = 30 meq/l E. [HCO 3 ]/[H 2 CO 3 ] ratio 22 CLINICAL STUDIES Practical PATHOPHYSIOLOGY 10. Given the following values: ph = 7,00 PaCO 2 = 52 mmhg HCO 3 = 13 mmol/l The most likely ABD is: A. De primary B. De primary C. Mixt D. A mixt ABD that combines a primary together with a primary E. An ABD that combines a primary together with a primary. 1. A 45 years old male patient is brought to the emergency room with a severe asthma decompensation. Arterial blood gas analysis shows: ph = 7,29 PaCO 2 = 62 mmhg [HCO 3 ] = 28 mmol/l Analyse the acidbase status and diagnose the ABD. Motivate your answer A 15 years old boy is brought to the hospital with severe vomiting. Arterial blood gas analysis shows: ph = 7,51 PaCO 2 = 49 mmhg [HCO 3 ] = 38 mmol/l Analyse the acidbase status and diagnose the ABD. Motivate your answer.... 7

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