Dr. Suzana Voiculescu
AB balance parameters Extracellular ph (plasmatic ph)= 7.35-7.45 < 7.35= acidosis >7.45= alkalosis
Kassirer-Bleich equation [H+] = 24 PCO2/ [HCO3-] predicts that the ratio of dissolved CO2 to HCO3-, rather than their actual concentrations, determines hydrogen ion concentration and thus ph.
A drop or rise in PCO2 will result in a drop or rise in [H+] respectively. [HCO3-] on the other hand is inversely related to H+ concentration whereby a drop in bicarbonate levels result in an increase in H+ concentration while a rise in bicarbonate levels result in a reduction in H+ concentration.
This buffer system is of physiologic importance because both the pulmonary and renal mechanisms for regulating ph work by adjusting this ratio. The PCO2 can be modified by changes in alveolar ventilation, while plasma [HCO3-] can be altered by regulating its generation and excretion by the kidneys.
The Henderson-Hasselbach equation The ratio of bicarbonate to carbonic acid determines the ph of the blood. Normally the ratio is about 20:1 bicarbonate to carbonic acid. This relationship is described in the Henderson- Hasselbach equation: ph = pk + log (HCO3-/H2CO3) (pk is the dissociation constant of the buffer, 6.10 at body temperature)
ph physiological variations: Age: newborn babies and children have a ph closer to the superior limit of the interval (7.42)- this favors anabolic processes (growth), while older people have more acidic ph due to the catabolic processes Digestion phases: gastric digestion, there is a more basic ph (elimination of H+ in the gastric secretions) intestinal digestion, the ph is more acid (HCO3- in the intestinal secretions)
ph physiological variations Circadian rhythm in the morning and at night- more acidic ph- CO2 accumulation during sleep Altitude- more basic ph-physiologic alkalosis- low po2 causes hyperventilation and low CO2. Effort- lactic acid
AB balance parameters Sampling of arterial blood Oxygenation of blood level through gas exchange in the lungs (SaO2, po2) CO2 elimination through respiration AB balance/imbalace in ECF
Oxygenation 4 ml/kg/min normal healthy person X10 fit X20 athletes Oxidative metabolism of carbohydrates/fats Co2 (15000-20000 meq/day) When hypoxia lactic acid Check if patient is breathing room air (21% O2) or not
Oxygenation po2 Normal= 100 mmhg young healthy adult breathing room air; falls with age (V/Q missmatch) po2= 104- (age x 0,27) Hypoxia po2< 90 mmhg Hyperoxia po2>100 mmhg SaO2 derived from po2 using Hb dissociation curve Hypoxia < 95%
AB balance parameters pco2= 38-42 mmhg= mean pressure of carbon dioxide in arterial blood Alkaline reserve= actual bicarbonate= 21-24 meq/l= content of HCO3- in patients blood at actual pco2; it represents the metabolic component of the buffer system, and it is usually modified by kidneys.
AB balance parameters ph Blood H+ conc= 0.00004 meq/l [H+] concentration is expressed on a logarithm scale as ph units
Standard bicarbonate [HCO3-] in standard conditions: standard pco2 and complete Hb oxygenation (thus eliminating the influence of the lungs on blood base concentration); normal values= 21-27 meq/l; What bicarbonate concentration would heve been after pco2 is corrected to 40 mmhg It is derived from actual bicarbonate value after changes associated with respiratory disturbances have been eliminated; reflects pure metabolic changes high [HCO3-] means metabolic alkalosis and low [HCO3-] means metabolic acidosis.
Base excess Base excess (BE)- the amount of base that needs to be removed to bring ph level back to normal when pco2 is corrected to 40 mmhg Negative (base deficit) in metabolic acidosis and positive in metabolic alkalosis. Normal value= +2.5-2.5 mmol/l.
Anionic gap Anionic gap- the difference between cations and anions which are normally determined in the plasma. AG = (Na + + K + ) [(Cl - ) + (HCO3 - )]; normal value = 16 ± 2 mmol/l. AG = (Na + ) [(Cl - ) + (HCO3 - )]; normal value= 12 ± 4 mmol/l. Corrected AG in case of low albumin level: AG corrected = AG + 0,25 (Albumin normal Albumin measured)
AB balance disorder An acid base disorder is a change in the normal value of extracellular ph that may result when renal or respiratory function is abnormal or when an acid or base load overwhelms excretory capacity. ph PCO2 HCO3- Range: 7.35-7.45 36-44 22-26 Optimal value 7.40 40 24
Acid base status is defined in terms of the plasma ph. Acidemia - decrease in the blood ph below normal range of 7.35-7.45 Alkalemia - Elevation in blood ph above the normal range of 7.35 7.45 Clinical disturbances of acid base metabolism classically are defined in terms of the HCO3- /CO2 buffer system. Acidosis process that increases [H+] by increasing PCO2 or by reducing [HCO3-] Alkalosis process that reduces [H+] by reducing PCO2 or by increasing [HCO3-]
IMPORTANT It is important to note that though acidosis and alkalosis usually leads to acidemia and alkalemia respectively, the exception occurs when there is a mixed acid base disorder. In that situation, multiple acid base processes coexisting may lead to a normal ph or a mixed picture
Respiratory versus metabolic Since PCO2 is regulated by respiration, abnormalities that primarily alter the PCO2 are referred to as respiratory acidosis (high PCO2) and respiratory alkalosis (low PCO2). In contrast, [HCO3-] is regulated primarily by renal processes. Abnormalities that primarily alter the [HCO3-] are referred to as metabolic acidosis (low [HCO3-]) and metabolic alkalosis (high [HCO3-]).
Simple vs mixed Simple acid base disorders : Disorders that are either metabolic or respiratory. Mixed acid base disorders: More than one acid base disturbance present. ph may be normal or abnormal
Compensation Acid Base disoders are associated with defense mechanisms referred to as compensatory responses that function to reduce the effects of the particular disorder on the ph. They do not restore the ph back to a normal value. This can only be done with correction of the underlying cause. In each of these disorders, compensatory renal or respiratory responses act to minimize the change in H+ concentration by minimizing the alteration in the PCO2 /[HCO3-] ratio.
Compensatory resposes 1. Compensatory responses never return the ph to normal. 2. The basis of compensatory responses is to maintain the PCO2/[HCO3-] ratio. 3. Therefore, the direction of the compensatory response is always the same as that of the initial change.
4. Compensatory response to respiratory disorders is two-fold; a fast response due to cell buffering and a significantly slower response due to renal adaptation. 5. Compensatory response to metabolic disorders involves mainly an alteration in alveolar ventilation. 6. Metabolic responses cannot be defined as acute or chronic in terms of respiratory compensation because the extent of compensation is the same in each case.
Respiratory acidosis Increase of pco2 in respiratory diseases Elevation in the PCO2/[HCO 3 -] ratio which subsequently increases the hydrogen ion concentration according to the following equation: [H+] = 24 PCO2 / [HCO3-] Compensation- increase of HCO3- by a) rapid cell buffering of H+ (HB and proteins) ACUTE H 2 CO 3 + Hb- HHb + HCO 3 - b) an increase in net acid excretion CHRONICAL
ACUTE vs CHRONIC Respiratory Acidosis ACUTE - buffers As shown above, each buffering reaction produces HCO 3 -, which leads to an increase in plasma [HCO 3 -]. Due to this process, acutely, there is an increase in the plasma [HCO 3 -], averaging 1 meq/l for every 10 mmhg rise in the PCO2. CHRONIC- kidneys A 3.5 meq/l increase in the plasma HCO3- concentration for every 10 mmhg increase in the PCO2; metabolic comp is not obvious for a few hours and takes 4 days to complete
Thus... Renal compensation offers more significant ph protection in the setting of chronic respiratory acidosis in contrast to intracellular buffering in the acute situation. Chronic respiratory acidosis is commonly caused by COPD. These patients can tolerate a PCO2 of up to 90-110 mmhg and not have a severe reduction in ph due to renal compensation.
Respiratory acidosis Causes: Alveolar hypoventilation CNS depression (meds, trauma) Miopathic diseases Restrictive pulmonary disease Obstructive pulmonary disease High CO2 production- hyper thyroidism, malignant hyperthermia, seizure VERY RARE
Respiratory alkalosis Decrease of pco2 due to hyperventilation is followed by increased ph. Net reduction in PCO2 and subsequently a reduction in the PCO2 / [HCO 3 -] ratio which reduces the hydrogen ion concentration (and increases the ph) according to the following equation: [H+] = 24 PCO2 / [HCO 3 -]
Respiratory alkalosis Compensation Rapid cell buffering ACUTE Kidneys decrease H+ secretion and increased HCO3- excretion. CHRONICAL Causes: Peripheric stimulation (hypoxemia, anemia, altitude) Central stimulation (pain, anxiety, meds) Metabolic encephalopathy (hepatic cirrhosis)
ACUTE Respiratory alkalosis About 10 minutes after the onset of respiratory alkalosis, hydrogen ions move from the cells into the extracellular fluid, where they combine with HCO 3 - The hydrogen ions are primarily derived from intracellular buffers such as hemoglobin, protein and phosphates. The reaction with bicarbonate ions in this reaction leads to a mild reduction in plasma [HCO 3 -]. In acute respiratory alkalosis, as a result of cell buffering, for every 10 mmhg decrease in the PCO2, there is a 2mEq/L decrease in the plasma HCO3- concentration.
CHRONIC Respiratory alkalosis If respiratory alkalosis persist for longer than 2-6 hours, the kidney will respond by lowering hydrogen secretion, excretion of titratable acids, ammonium production and ammonium excretion. There will also be an increase in the amount of HCO3 in the urine- excreted due to decreased reabsorption of filtered HCO 3 -. Completion of this process occurs after 2-3 days after which a new steady state is achieved. Renal compensation result in a 4 meq/l reduction in plasma [HCO 3 -] for every 10 mmhg reduction in PCO2.
Metabolic acidosis Decrease in [HCO3-] followed by plasma ph decrease. Elevation in the PCO2/HCO3- ratio and thus an elevation in hydrogen ion concentration according to the following equation: [H+] = 24 (PCO2 / [HCO3-]) Compensation Respiratory- LOW CO2 through hyperventilation Renal- if the cause is not kidney disfunction- H+ excretion enhanced high ammonia (NH4+)
The reduction in PCO2 is accomplished by increasing alveolar ventilation- quick response The drop in arterial ph stimulates central and peripheral chemoreceptors controlling respiration, resulting in an increase in alveolar ventilation. The increase in ventilation is characterized more by an increase in tidal volume than by an increase in respiratory rate, and may if the acidemia is severe, reach a maximum of 30L/min (nl = 5-6 L/min).
Kussmaul breathing Kussmaul breathing is respiratory compensation for a metabolic acidosis, most commonly occurring in diabetics in diabetic ketoacidosis. https://www.youtube.com/watch?v=tg0vpkae3js
Metabolic acidosis causes 1. most frequent Increased extracellular buffering of an increased acid load 2. less frequent loss of bicarbonate ions in the urine
Cause evaluation of metabolic acidosis Anionic gap= Na+ - [Cl- - HCO3-]= 12 +/- 4 High AG= H+ excess AG = (Na + ) [(Cl - ) + (HCO3 - )] Exogenous intoxication (ethylene glycol, salicylates, methanol) Endogenous ketoacidosis, lactic acidosis, renal failure Normal AG (hyperchloremic acidosis)= HCO3- loss AG normala = (Na + ) [(Cl - ) + (HCO3 - )] Organism retains one Cl- for each lost HCO3- Digestive (intestinal fluid) Renal (renal tubular acidosis)
If metabolic acidosis with high anionic gap- Delta ration
If metabolic acidosis with normal AG- renal or digestive?? Urinary Anionic Gap= UAG Cations in the urine Na +, K +, NH 4+, Ca ++, Mg ++. Anions in urina Cl -, HCO 3-, sulfate, phosphate, organic. Usually measured Na +, K +, Cl- The unmeasured ones= UA/UC (unmeasured A/C) Cl- + UA = Na + + K + + UC UA-UC= [Na + ]+ [K + ] - [Cl - ] Urinary Anion Gap normal value >0
UAG Index of NH4+ excretion in the urine If digestive loss of bases (extrarenal) normal renal function urinary ammonia excretion UAG <0 If renal loss of bases- kidneys cannot eliminate the excess H+ through ammonia low ammonia excretion UAG >0
UAG Hyperchloremic metabolic acidosis: UAG <0 bicarbonate digestive loss UAG> 0 loss of renal acidifiation capacity negutive - negative UAG in bowel (GUT) causes.
Metabolic alkalosis Increased [HCO3-], followed by increased arterial blood ph. [H+] = 24 (PCO2 / [HCO3-]) organism tries to increase pco2 low alveolar ventilation Compensation: Respiratory- hypoventilation On average the pco2 rises 0.7 mmhg for every 1.0 meq/l increase in the plasma [HCO3-].
Metabolic alkalosis Causes: Digestive loss (gastric acid) Renal loss (diuretics) Primary hyperaldosteronism Next? Cause evaluation
Cause evaluation in metabolic alkalosis Cl responsive- urinary Cl < 20 meq/l Digestive- gastric acid loss (vomiting) Renal use of diuretics Cl unresponsive- urinary Cl> 20 meq/l Endocrine- primary hyperaldosteronism
Cause evaluation in metabolic alkalosis Cl responsive-urinary Cl < 20 meq/l Digestive- vomiting- gastric acid loss (loss of fluid and NaCl higher HCO3- reabsoption to compensate Clloss) Renal- diuretics (Cl- loss in the urine)- furosemide, thiazide Cl unresponsive- urinary Cl > 20 meq/l Endocrine- primary hyperadosteronism
Mixed Mixed acid base disorders occur when there is more than one primary acid base disturbance present simultaneously. They are frequently seen in hospitalized patients, particularly in the critically ill.
When to suspect a mixed acid base disorder: The expected compensatory response does not occur Compensatory response occurs, but level of compensation is inadequate or too extreme Whenever the PCO2 and [HCO3-] becomes abnormal in the opposite direction. (i.e. one is elevated while the other is reduced). In simple acid base disorders, the direction of the compensatory response is always the same as the direction of the initial abnormal change. ph is normal but PCO2 or HCO3- is abnormal In simple acid base disorders, the compensatory response should never return the ph to normal. If that happens, suspect a mixed disorder.
Steps to follow in diagnosis of AB disorders 1. ph evaluation- acidosis or alkalosis 2. establish cause- metabolic/respiratory in simple ones 3. compensation degree present/absent 4. AG calculus If metabolic acidosis If AG is high delta ratio If AG is normal- Urinary AG- renal or digestive? 5. Urinary Cl If metabolic alkalosis 6. think of possible diagnosis and order further tests
Case study A 50 year old man came to emergency department after returning from foreign travel. His symptom included persistent diarrhea (over the past 3 days) and rapid respiration. Blood gases were drawn with following results : ph- 7.21 ( ) pco2-19 mmhg ( ) po2-96 mmhg HCO3-7 mmol/l Questions: 1. What is the patient acid base status? 2. Why is the HCO3 level is so low? 3. Why does the patient have rapid respiration?
Clinical case 1 A 44 year old moderately dehydrated man was admitted with a two day history of acute severe diarrhea. Electrolyte results: Na+ 134, K+ 2.9, Cl- 108, HCO3-16, BUN 31, Cr 1.5. ABG: ph 7.31 pco2 33 mmhg HCO3 16 po2 93 mmhg
Is compensation adequate? Estimated PCO2 = 1.5 [HCO3-]) + 8 ± 2 = 1.5 16 + 8 ± 2 = 30-34. So... Respiratory compensation is present (no respiratory disorder is present)
Clinical case 2 A 22 year old female with type I DM, presents to the emergency department with a 1 day history of nausea, vomiting, polyuria, polydypsia and vague abdominal pain. P.E. noted for deep sighing breathing, orthostatic hypotension, and dry mucous membranes
Labs: Na 132, K 6.0, Cl 93, HCO3-11 glucose 720, BUN 38, Cr 2.6. Urine: ph 5, SG 1.010, ketones negative, glucose positive. Plasma ketones trace. Acid base: ph 7.27 HCO3-10 PCO2 23
Likely ab disorders based on clinical scenario Elevated anion gap acidosis secondary to DKA, or Elevated anion gap acidosis secondary to lactic acidosis in the setting of vomiting and polyuria which may lead to hypovolemia, and/or Metabolic alkalosis in the setting of vomiting
First step- ph ACIDOSIS How to distinguish initial change from compensatory response? Low HCO3- is consistent with ph change initial change To maintain the PCO2/HCO3-, the PCO2 is reduced in response
Diagnostic- METABOLIC ACIDOSIS Calculate the anion gap The anion gap is Na - (Cl + HCO3-) = 132 -(93 + 11) = 28 Since gap is greater than 16, it is therefore HIGH.
Is compensation adequate? PCO2 = 1.5 [HCO3-]) + 8 ± 2 = 1.5 11 + 8 ± 2 = 22.5-26.5. Since the actual PCO2 falls within the estimated range, we can deduce that the compensation is adequate and there is no separate respiratory disorder present. Compensated high anionic gap metabolic acidosis (diabetic ketoacidosis)
!! Note the absence of ketones in the urine. This is sometimes seen in early DKA due to the predominance of beta-hydroxybutyrate. The dipstick test for ketones detect acetoacetate but not beta-hydroxybutyrate.
Clinical case 3 A previously well 55 year old woman is admitted with a complaint of severe vomiting for 5 days. Physical examination reveals postural hypotension, tachycardia, and diminished skin turgor. The laboratory finding include the following: Electroyes: Na 140, K 3.4, Cl 77 HCO3-9, Cr 2.1 ABG: ph 7.23, PCO2 22mmHg
Likely ab disorders Elevated anion gap acidosis secondary to lactic acidosis in the setting of severe persistent vomiting which may lead to hypovolemia, and/or Metabolic alkalosis in the setting of persistent vomiting The ph is low, (less than 7.35) therefore by definition, patient is acidemic.
What is the process? Look at the PCO2, HCO3-. PCO2 and HCO3- are abnormal in the same direction, therefore less likely a mixed acid base disorder but not yet ruled out. Need to distinguish the initial change from the compensatory response Low HCO3- represents acidosis and is consistent with the ph, therefore it must be the initial change. The low PCO2 must be the compensatory response.
Anionic gap The anion gap is Na - (Cl + HCO3-) = 134 -(77 + 9) = 48 Since gap is greater than 16, it is therefore abnormal.
Is compensation adequate PCO2 = 1.5 [HCO3-]) + 8 ± 2 = 1.5 9 + 8 ± 2 = 19.5-23.5. Since the actual PCO2 falls within the estimated range, we can deduce that the compensation is adequate and there is no separate respiratory disorder present.
Delta ratio Delta ratio= delta AG/ delta [HCO3-]= DR= AG-12/ 24-[HCO3-]= 48-12/24-9= 2.6 Concurrent metabolic alkalosis (vomiting) Mixed elevated anion gap metabolic acidosis and metabolic alkalosis likely due to lactic acidosis and vomiting.
Clinical case 4 A 70 year old man with history of CHF presents with increased shortness of breath and leg swelling. ABG: ph 7.24, PCO2 60 mmhg, PO2 52 HCO3 27
ph The ph is low, (less than 7.35) therefore by definition, patient is acidemic. PCO2 and HCO3- are abnormal in the same direction, therefore less likely a mixed acid base disorder but not yet ruled out. HCO3- is on the high side of normal and is not consistent with the ph. PCO2 is high and represents acidosis and is consistent with the ph. Therefore it must be the initial change. The high normal HCO3- must be the compensatory response= RESPIRATORY ACIDOSIS
Clincal case 5 A 28 year old female with history of Sjogren s syndrome presents to her PCP for a check up visit. In review of systems, she reports a 2 day episode of watery diarrhea 2 days ago. She is otherwise doing well. Physical examination is unremarkable. She is noted to have the following serum chemistry: Na 138, K 4.2, Cl 108, HCO3-14
Urine Because of her history, the physician decides to check her urine electrolytes. Urine chemistry: K 31, Na 100, Cl 105
Note that in this scenario, we are not given an arterial blood gas. Therefore we must deduce the diagnosis primarily from the history and the limited workup available.
The patients presents to an outpatient visit very asymptomatic. Besides the history of diarrhea, there is nothing else in the history to suggest an active acid base disorder. However, her serum electrolytes indicate a low HCO3- concentration which suggests acidosis. We can safely rule out a chronic respiratory alkalosis as basis of the low HCO3- since hyperventilation would be evident on exam. In the absence of other data, we have to assume that the patient has a metabolic acidosis.
We are not given serum electrolytes and therefore we cannot calculate the anion gap, Based on the history, we can assume that the patient does not have lactic acidosis, ketoacidosis, uremia and has not ingested any toxins.
Assuming the patient has normal anion gap acidosis, our differential becomes diarrhea vs RTA. We have to consider RTA in this patient, because of the history of Sjogren's.
UAG UAG = Na + K - Cl UAG = 100 + 31-105 = 26. A positive UAG suggest RTA because in the setting of diarrhea, ammonium chloride concentration in the urine would be high and the UAG would be negative. A postive value suggests that the kidney is unable to adequately excrete ammonium, leading to a reduction in net acid excretion and thus metabolic acidosis. Metabolic acidosis likely secondary to renal tubular acidosis.