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Conditions Invalidating or Modifying ABG Results:

Conditions Invalidating or Modifying ABG Results DELAYED ANALYSIS Consumptiom of O2 & Production of CO2 continues after blood drawn into syringe Iced Sample maintains values for 1-2 hours Uniced sample quickly becomes invalid PaCO2  3-10 mmHg/hour PaO2  at a rate related to initial value & dependant on Hb Sat

Slide 3:

Parameter 37 C (Change every 10 min) 4 C (Change every 10 min)  pH 0.01 0.001  PCO2 1 mm Hg 0.1 mm Hg  PO2 0.1 vol % 0.01 vol % EFFECT OF TEMP ON RATE OF CHANGE IN ABG VALUES

Slide 4:

EXCESSIVE HEPARIN Dilutional effect on results  HCO 3 - & PaCO2 Syringe be emptied of heparin after flushing Risk of alteration of results  with:  size of syringe/needle  vol of sample 25% lower values if 1ml sample taken in 10 ml syringe (0.25 ml heparin in needle) Syringes must be > 50% full with blood sample HYPERVENTILATION OR BREATH HOLDING May lead to erroneous lab results

Slide 5:

AIR BUBBLES PO2 150 mmHg & PCO2 0 mm Hg in air bubble(R.A.) Mixing with sample lead to  PaO2 &  PaCO2 Mixing/Agitation  S.A. for diffusion  more erroneous results Discard sample if excessive air bubbles Seal with cork/cap imm after taking sample FEVER OR HYPOTHERMIA Most ABG analyzers report data at N body temp If severe hyper/hypothermia, values of pH & PCO2 at 37 C can be significantly diff from pt’s actual values Changes in PO2 values with temp predictable

Slide 6:

No significant change of HCO3-, O2 Sat, O2 capacity/content, CO2 content values with temp No consensus regarding reporting of ABG values esp pH & PCO2 after doing ‘temp correction’ ? Interpret values measured at 37 C: Most clinicians do not remember normal values of pH & PCO2 at temp other than 37C In pts with hypo/hyperthermia, body temp usually changes with time (per se/effect of rewarming/cooling strategies) – hence if all calculations done at 37 C easier to compare Values other than pH & PCO2 do not change with temp Hansen JE, Clinics in Chest Med 10(2), 1989 227-237

Slide 7:

? Use Nomogram to convert values at 37C to pt’s temp Some analysers calculate values at both 37C and pt’s temp automatically if entered Pt’s temp should be mentioned while sending sample & lab should mention whether values being given in report at 37 C/pts actual temp WBC COUNT 0.1 ml of O2 consumed/dL of blood in 10 min in pts with N TLC Marked increase in pts with very high TLC/plt counts – hence imm chilling/analysis essential

Slide 8:

TYPE OF SYRINGE pH & PCO2 values unaffected PO2 values drop more rapidly in plastic syringes (ONLY if PO2 > 400 mm Hg) Other adv of glass syringes: Min friction of barrel with syringe wall Usually no need to ‘pull back’ barrel – less chance of air bubbles entering syringe Small air bubbles adhere to sides of plastic syringes – difficult to expel Though glass syringes preferred, differences usually not of clinical significance  plastic syringes can be and continue to be used

Slide 9:

QUALITY CONTROL & CALIBRATION Mechanism of Measurement & Electronic Drift in electrodes Measurement of voltages (potentiometric) – Balance Drift (Shifting of calibration points from baseline though maintain same slope) Sanz (pH) electrode Severinghaus/Stow (PCO2) electrode Measurement of amperage (amperometric) – Slope Drift (Angle of calibration points changes though baseline remains same) Clark (PO2) electrode Recommendations for calibration of each electrode – 2 point calibration every 8 hrs 1 point calibration every 4 hrs

Approach to ABG Interpretation:

Approach to ABG Interpretation Assessment of the type of acid base disorder requires at a minimum 2 of the following: Arterial pH pCO2 plasma HCO 3 - Complete analysis of an ABG requires: pH pO2 pCO2 HCO 3 - O2 Sat BE/BD Anion Gap (AG)  AG  HCO 3 -

Assessment of Oxygenation Status:

Assessment of Oxygenation Status

Arterial Oxygen Tension (PaO2):

Arterial Oxygen Tension (PaO2) Normal value in healthy adult breathing room air at sea level  97 mm Hg.  progressively with  age Dependant upon FiO2 P atm Hypoxemia is PaO2 < 80 mm Hg at RA Most pts who need ABG usually req O2 therapy O2 therapy should not be withheld/interrupted ‘to determine PaO2 on RA’

Acceptable PaO2 Values on Room Air:

Acceptable PaO2 Values on Room Air Age Group Accepable PaO2 (mm Hg) Adults upto 60 yrs & Children > 80 Newborn 40-70 70 yrs > 70 80 yrs > 60 90 yrs > 50 60 yrs  80 mm Hg   1mm Hg/yr

Inspired O2 – PaO2 Relationship:

Inspired O2 – PaO2 Relationship FIO2 (%) Predicted Min PaO2 (mm Hg) 30 150 40 200 50 250 80 400 100 500 If PaO2 < FIO2 x 5, pt probably hypoxemic at RA

Hypoxemia on O2 therapy:

Hypoxemia on O2 therapy Uncorrected: PaO2 < 80 mm Hg (< expected on RA & FIO2) Corrected: PaO2 = 80-100 mm Hg (= expected on RA but < expected for FIO2) Excessively Corrected: PaO2 > 100 mm Hg (> expected on RA but < expected for FIO2) PaO2 > expected for FIO2: 1. Error in sample/analyzer 2. Pt’s O2 consumption reduced 3. Pt does not req O2 therapy (if 1 & 2 NA)

Assessment of Acid-Base Status:

Assessment of Acid-Base Status

Bicarbonate (HCO3-):

Bicarbonate (HCO 3 - ) Std HCO 3 - : HCO 3 - levels measured in lab after equilibration of blood PCO2 to 40 mm Hg (  routine measurement of other serum electrolytes) Actual HCO 3 - : HCO 3 - levels calculated from pH & PCO2 directly Reflection of non respiratory (metabolic) acid-base status. Does not quantify degree of abnormality of buffer base/actual buffering capacity of blood.

Base Excess/Base Deficit:

Base Excess/Base Deficit Calculated from pH, PaCO2 and HCT Expressed as meq/L of base above N buffer base range Negative BE also referred to as Base Deficit True reflection of non respiratory (metabolic) acid base status


DEFINITIONS AND TERMINOLOGY 3 Component Terminology – Compensated/Uncompensated Respiratory/Metabolic Acidosis/Alkalosis ACIDEMIA – reduction in arterial pH    (pH<7.35) ALKALEMIA – increase in arterial pH (pH>7.45) ACIDOSIS – presence of a process which tends to  pH by virtue of gain of H + or loss of HCO 3 - ALKALOSIS – presence of a process which tends to  pH by virtue of loss of H + or gain of HCO 3 -

Slide 20:

RESPIRATORY VS METABOLIC Respiratory – processes which lead to acidosis or alkalosis through a primary alteration in ventilation and resultant excessive elimination or  retention of CO2 Metabolic – processes which lead to acidosis or alkalosis through their effects on kidneys and the consequent disruption of H + and HCO 3 - control

Slide 21:

COMPENSATION – The normal response of the  respiratory system or kidneys to change in pH induced by a primary acid-base disorder SIMPLE VS. MIXED ACID-BASE DISORDER Simple acid-base disorder – a single primary process  of acidosis or alkalosis Mixed acid-base disorder – presence of more than one acid base disorder simultaneously

Slide 22:

Characteristics of  acid-base disorders DISORDER PRIMARY RESPONSES COMPENSATORY RESPONSE Metabolic acidosis  [H + ]  PH  HCO 3 -  pCO2 Metabolic alkalosis  [H + ]  PH  HCO 3 -  pCO2 Respiratory acidosis  [H + ]  PH  pCO2  HCO 3 - Respiratory alkalosis  [H + ]  PH  pCO2  HCO 3 -

Compensation :

Compensation In the presence of acidosis or alkalosis, regulatory mechanisms occur which attempt to maintain the arterial pH in the physiologic range. These processes result in the return of pH towards, but generally just outside the normal range Disturbances in HCO3- (metabolic acidosis or alkalosis) result in respiratory compensation while changes in CO2 (respiratory acidosis/alkalosis) are counteracted by renal compensation a. Renal compensation – kidneys adapt to alterations in pH by changing the amount of HCO3- generated/excreted. Full renal compensation takes 2-5 days b. Respiratory compensation – alteration in ventilation allow immediate compensation for metabolic acid-base disorders

Slide 24:

RENAL & RESPIRATORY COMPENSATIONS TO  ACID-BASE DISTURBANCES Disorder Compensatory response Metabolic acidosis PCO 2  1.2 mmHg per 1.0 meq/L  HCO 3 - Metabolic alkalosis PCO 2  0.7 mmHg per 1.0 meq/L  HCO 3 - Respiratory acidosis [HCO 3 - ]  Acute 1.0 meq/L per 10 mmHg  Pco 2 Chronic 3.5 meq/L per 10 mmHg  Pco 2 Respiratory alkalosis [HCO 3 - ]  Acute 2.0 meq/L per 10 mmHg  Pco 2 Chronic 4.0 meq/L per 10 mmHg  Pco 2

Stepwise approach to ABG Analysis:

Stepwise approach to ABG Analysis Determine whether patient is alkalemic or acidemic using the arterial pH measurement Determine whether the acid-base disorder is a primary respiratory or metabolic disturbance based on the pCO2 and serum HCO 3 - level If a primary respiratory disorder is present, determine whether it is chronic or acute In metabolic disorders, determine if there is adequate compensation of the respiratory system In respiratory disorders, determine if there is adequate compensation of the metabolic system

Slide 26:

Determine pt’s oxygenation status (PaO2 & SaO2) – hypoxemic or not If a metabolic acidosis is present, determine the anion gap and osmolar gap In high anion gap acidosis, determine the change in anion gap (  AG) &  HCO 3 - in order to assess for the presence of coexisting metabolic disturbances In normal (non) anion gap acidosis, determine the urinary anion gap - helpful to distinguish renal from non renal causes

Interpretation: pH:

Interpretation: pH Normal arterial pH = 7.36 to 7.44 Determine Acidosis versus Akalosis 1. pH <7.35: Acidosis 2. pH >7.45: Alkalosis Metabolic Conditions are suggested if pH changes in the same direction as pCO2/HCO3- pH is abnormal but pCO2 remains unchanged Respiratory Conditions are suggested if: pH changes in the opp direction as pCO2/HCO3- pH is abnormal but HCO3- remains unchanged

Slide 28:

pH  N  Acidemia Resp and/or Met Acidosis Alkalemia Resp and/or Met Alkalosis No acidemia /alkalemia Resp Acidosis and Met Alkalosis Met Acidosis and Resp Alkalosis No A-B Dis

Slide 29:

pH  pCO2 , HCO3  pCO2 , HCO3 N Resp + Met Alkalosis Uncomp Resp Alkalosis pCO2 N , HCO3  Uncomp Met Alkalosis pCO2 , HCO3  Comp(F/P) Met Alkalosis pCO2 , HCO3  Comp(F/P) Resp Alkalosis

Slide 30:

pH  pCO2 , HCO3  pCO2 , HCO3 N Resp + Met Acidosis Uncomp Resp Acidosis pCO2 N , HCO3  Uncomp Met Acidosis pCO2 , HCO3  Comp(F/P) Resp Acidosis pCO2 , HCO3  Comp(F/P) Met Acidosis

Slide 31:

pH N or N pCO2 , HCO3  Comp(F) Met Alkalosis pCO2 N , HCO3 N N Acid Base Homeostasis pCO2 , HCO3  Met acidosis + Resp alkalosis Comp(F) Met Acidosis Comp(F) Resp Alkalosis Comp(F) Resp Acidosis Resp Acidosis + Met Alkalosis

Respiratory Acid Base Disorders:

Respiratory Acid Base Disorders Respiratory alkalosis most common of all the 4 acid base disorders (23-46%) -followed by met alkalosis - review of 8289 ABG analysis in ICU pts Kaehny WD, MCNA 67(4), 1983 p 915-928 Resp acidosis seen in 14-22% of pts Attention to possibility of hypoxemia and its correction always assumes priority in analysis of pts with a possible respiratory acid-base disorder



Causes of Respiratory Alkalosis:

Causes of Respiratory Alkalosis CENTRAL RESPIRATORY STIMULATION (Direct Stimulation of Resp Center): Structural Causes Non Structural Causes Head trauma Pain Brain tumor Anxiety CVA Fever Voluntary PERIPHERAL RESPIRATORY STIMULATION (Hypoxemia  Reflex Stimulation of Resp Center via Peripheral Chemoreceptors ) Pul V/Q imbalance Pul Diffusion Defects Hypotension Pul Shunts High Altitude

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INTRATHORACIC STRUCTURAL CAUSES: Reduced movement of chest wall & diaphragm Reduced compliance of lungs Irritative lesions of conducting airways MIXED/UNKNOWN MECHANISMS: Drugs – Salicylates Nicotine Progesterone Thyroid hormone Catecholamines Xanthines (Aminophylline & related compounds) Cirrhosis Gram –ve Sepsis Pregnancy Heat exposure Mechanical Ventilation

Manifestations of Resp Alkalosis:

Manifestations of Resp Alkalosis NEUROMUSCULAR: Related to cerebral A vasoconstriction &  Cerebral BF Lightheadedness Confusion Decreased intellectual function Syncope Seizures Paraesthesias (circumoral, extremities) Muscle twitching, cramps, tetany Hyperreflexia Strokes in pts with sickle cell disease

Slide 37:

CARDIOVASCULAR: Related to coronary vasoconstriction Tachycardia with  N BP Angina ECG changes (ST depression) Ventricular arrythmias GASTROINTESTINAL: Nausea & Vomitting (cerebral hypoxia) BIOCHEMICAL ABNORMALITIES:  tCO2 PO 4 3- Cl -  Ca 2+

Homeostatic Response to Resp Alkalosis:

Homeostatic Response to Resp Alkalosis In ac resp alkalosis, imm response to fall in CO2 (& H2CO3)  release of H+ by blood and tissue buffers  react with HCO3-  fall in HCO3- (usually not less than 18) and fall in pH Cellular uptake of HCO3- in exchange for Cl- Steady state in 15 min - persists for 6 hrs After 6 hrs kidneys increase excretion of HCO3- (usually not less than 12-14) Steady state reached in 1 1/2 to 3 days. Timing of onset of hypocapnia usually not known except for pts on MV. Hence progression to subac and ch resp alkalosis indistinct in clinical practice

Treatment of Respiratory Alkalosis:

Treatment of Respiratory Alkalosis Resp alkalosis by itself not a cause of resp failure unless work of increased breathing not sustained by resp muscles Rx underlying cause Usually extent of alkalemia produced not dangerous. Admn of O2 if hypoxaemia If pH>7.55 pt may be sedated/anesthetised/ paralysed and/or put on MV.

Pseudorespiratory Alkalosis :

Pseudorespiratory Alkalosis Arterial hypocapnia can be observed in an idiotypic form of respiratory acidosis. Occurs in patients with profound depression of cardiac function and pulmonary perfusion but with relative preservation of alveolar ventilation ( incl pts undergoing CPR). Severely reduced pul BF limits CO2 delivered to lungs for excretion   PvCO2 . Increased V/Q ratio causes removal of a larger-than-normal amount of CO2 per unit of blood traversing the pulmonary circulation  arterial eucapnia or frank hypocapnia.

Slide 41:

Absolute excretion of CO2 decreased and CO2 balance of body +ve — the hallmark of respiratory acidosis. Pts may have severe venous acidemia (often due to mixed respiratory and metabolic acidosis) accompanied by an arterial pH that ranges from mildly acidic to the frankly alkaline. Extreme oxygen deprivation prevailing in the tissues may be completely disguised by the reasonably preserved values of arterial oxygen. To rule out pseudorespiratory alkalosis in a patient with circulatory failure, blood gas monitoring must include sampling of mixed (or central) venous blood. Mx must be directed toward optimizing systemic hemodynamics.



Causes of Acute Respiratory Acidosis:

Causes of Acute Respiratory Acidosis EXCRETORY COMPONENT PROBLEMS: Perfusion: Massive PTE Cardiac Arrest Ventilation: Severe pul edema Severe pneumonia ARDS Airway obstruction Restriction of lung/thorax: Flail chest Pneumothorax Hemothorax Bronchospasm (severe) Aspiration Laryngospasm OSA

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Muscular defects: Severe hypokalemia Myasthenic crisis Failure of Mechanical Ventilator CONTROL COMPONENT PROBLEMS: CNS: CSA Drugs (Anesthetics, Sedatives) Trauma Stroke Spinal Cord & Peripheral Nerves: Cervical Cord injury LGBS Neurotoxins (Botulism, Tetanus, OPC) Drugs causing Sk. m.paralysis (SCh, Curare, Pancuronium & allied drugs, aminoglycosides)

Causes of Chronic Respiratory Acidosis:

Causes of Chronic Respiratory Acidosis EXCRETORY COMPONENT PROBLEMS: Ventilation: COPD Advanced ILD Restriction of thorax/chest wall: Kyphoscoliosis, Arthritis Fibrothorax Hydrothorax Muscular dystrophy Polymyositis

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CONTROL COMPONENT PROBLEMS: CNS: Obesity Hypoventilation Syndrome Tumours Brainstem infarcts Myxedema Ch sedative abuse Bulbar Poliomyelitis Spinal Cord & Peripheral Nerves: Poliomyelitis Multiple Sclerosis ALS Diaphragmatic paralysis

Manifestations of Resp Acidosis:

Manifestations of Resp Acidosis NEUROMUSCULAR: Related to cerebral A vasodilatation &  Cerebral BF Anxiety Asterixis Lethargy, Stupor, Coma Delirium Seizures Headache Papilledema Focal Paresis Tremors, myoclonus

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CARDIOVASCULAR: Related to coronary vasodilation Tachycardia with  N BP Ventricular arrythmias (related to hypoxemia and not hypercapnia per se) Senstivity to digitalis BIOCHEMICAL ABNORMALITIES:  tCO2  Cl -  PO 4 3-

Homeostatic Response to Respiratory Acidosis:

Homeostatic Response to Respiratory Acidosis Imm response to rise in CO2 (& H2CO3)  blood and tissue buffers take up H+ ions, H2CO3 dissociates and HCO3- increases with rise in pH. Steady state reached in 10 min & lasts for 8 hours. PCO2 of CSF changes rapidly to match PaCO2. Hypercapnia that persists > few hours induces an increase in CSF HCO3- that reaches max by 24 hr and partly restores the CSF pH. After 8 hrs, kidneys generate HCO3- Steady state reached in 3-5 d

Slide 50:

Alveolar-gas equation predicts rise in PaCO2  obligatory hypoxemia in pts breathing R.A. Resultant fall in PaO2 limits hypercapnia to  80 to 90 mm Hg Higher PaCO2 leads to PaO2 incompatible with life. Hypoxemia, not hypercapnia or acidemia, that poses the principal threat to life. Consequently, oxygen administration represents a critical element in the management

Treatment of Respiratory Acidosis:

Treatment of Respiratory Acidosis Ensure adequate oxygenation - care to avoid inadequate oxygenation while preventing worsening of hypercapnia due to supression of hypoxemic resp drive Correct underlying disorder if possible Avoid rapid decrease in ch elevated PCO2 to avoid post hypercapnic met alkalosis (arrythmias, seizures  adequate intake of Cl-)

Slide 52:

Alkali (HCO3) therapy rarely in ac and never in ch resp acidosis  only if acidemia directly inhibiting cardiac functions Problems with alkali therapy: Decreased alv ventilation by decrease in pH mediated ventilatory drive Enhanced carbon dioxide production from bicarbonate decomposition Volume expansion. COPD pts on diuretics who develop met alkalosis often benfefited by acetazolamide





Slide 55:

ACID PRODUCTION Volatile Acids – metabolism produces 15,000-20,000 mmol of CO2 per day. Henderson Hasselbach Equation pH = pK + log base acid pH = 6.1 + log HCO 3 - H 2 CO 3 pH = 6.1 + log HCO 3 - 0.03 pCO 2 H + = 24 x pCO 2 HCO 3 - Free H+ will be produced if the CO2 is not eliminated. Overview of Acid-Base Physiology

Slide 56:

Non-Volatile Acids – 50-100 meq/day of non-volatile acids produced daily. The primary source is from metabolism of sulfur containing amino acids (cystine, methionine) and resultant formation of sulfuric acid. Other sources are non metabolized organic acids, phosphoric acid and other acids

Slide 57:

Range of ECF [H+] variation very small pH Vs. [H+] pH nanoeq [H+]/L 7.00-7.38 Acidemia 100-44 7.38-7.44 Normal 44-36 7.44-7.80 Alkalemia 36-16 Relationship between pH and [H] at physiologic pH pH 7.00 7.10 7.20 7.30 7.40 7.50 7.60 7.70 [H+] (nM) 100 79 63 50 40 32 25 20

Importance of pH Control:

Importance of pH Control pH (intracellular and ECF incl blood) maintained in narrow range to preserve N cell, tissue and organ f x Intracellular pH (pH i ) Maintanined at  7.2: To keep imp metabolic intermediates in ionized state and limit tendency to move out of cell Most intracellular enzymes taking part in cellular metabolism have pH optimum close to this value DNA, RNA & Protein synthesis  at slightly higher pH

Slide 59:

Maintained with help of plasma memb H+/base transporters (activated in response to acidemia) Blood pH Maintanined at  7.4: To keep pH i in optimal range Enable optimal binding of hormones to receptors Enable optimal activity of enzymes present in blood Kraut et al AJKD 2001; 38(4): 703-727

Slide 60:

1. BUFFERS – presence of buffer systems minimize the change in pH resulting from production of acid and provide imm protection from acid load. Main buffer system in humans is HCO3- HCO 3 - + H +  H2CO 3  H 2 O + CO 2 2. ROLE OF THE RESPIRATORY SYSTEM – elimination  of volatile acid -- CO2. a. Respiratory centers in the brain respond  to changes in pH of CSF and blood to  affect ventilatory rate. b. Ventilation directly controls the elimination of CO2. Regulation of arterial pH

Slide 61:

3. ROLE OF THE KIDNEY - To retain and regenerate HCO3- thereby regenerating the body buffer with the net effect of eliminating the non-volatile acid load a. H+ secretion 1. Free urinary H+ - minimal contribution 2. Ammonia 3. Phosphorus b. HCO3- reabsorption 1. Proximal tubule – 90% 2. Distal tubule Factors affecting H+ secretion/reabsorption HCO3- a. CO2 concentration, pH b. Aldosterone d. Potassium concentration c. ECF volume e. Chloride

Anion Gap:

Anion Gap AG traditionally used to assess acid-base status esp in D/D of met acidosis  AG &  HCO 3 - used to assess mixed acid-base disorders AG based on principle of electroneutrality: Total Serum Cations = Total Serum Anions Na + (K + Ca + Mg) = HCO3 + Cl + (PO4 + SO4 + Protein + Organic Acids) Na + UC = HCO3 + Cl + UA Na – (HCO3 + Cl) = UA – UC Na – (HCO3 + Cl) = AG

Slide 63:

Normal value of AG = 12 +/- 4 meq/L Revised N value AG = 8 +/- 4 meq/L Changes in methods of measurement of Na, Cl & HCO3 and resultant shift of Cl value to higher range.

Limiting factors for AG:

Limiting factors for AG LABORATORY VARIATIONS – Variations in normal reference range of components of AG to be taken into consideration. Each institution should assign a normal range for AG based on these values. INHERENT ERRORS IN CALCULATION – All limits of components valid for 95% of N population. Probability of false +ve determination for each variable (Na/Cl/HCO3) = 0.05 Probability of false +ve determination for AG = 3 x 0.05 = 0.15

Slide 65:

HYPOALBUMINEMIA - Pts with lowS. albumin can have high AG acidosis, but measured AG may be N becuase albumin has many -ve surface charges & accounts for a significant proportion of AG. Severe hypoalbuminemia may exhibit N AG as low as 4. Therefore in severe hypoalbuminemia if AG is normal, one must suspect an additional metabolic cause for increased AG ALKALOSIS -Alkalemic patients with pH > 7.5, AG may be  due to met alkalosis per se & not because of additional met acidosis. Reasons proposed for the same include:

Slide 66:

Surface charges on albumin become more -ve in alkalemic conditions (due to loss of protons) -->  unmeasured anions Assoc vol contraction --> hyperproteinemia Induction of glycolysis and resultant hyperlactatemia HYPERCALCEMIA - Fall in AG as expected (  UC) except in paraneoplastic hypercalcemia for unknown reasons Oster et al. Nephron 1990; 55:164-169. DRUGS - Lithium and polymyxin cause fall in AG (  UC) while carbenicillin cause  in AG (act as UA)

Slide 67:

CLEARANCE OF ANIONS - Pts with expected  AG acidosis may have N AG because of clearance of added anions e.g. DKA pts in early stage with adequate clearance of ketones may have a normal AG as also those in recovey phase  AG -  HCO 3 - RELATIONSHIP - used to assess mixed acid-base disorders in setting of high AG Met Acidosis:  AG/ HCO 3 - = 1  Pure High AG Met Acidosis  AG/ HCO 3 - > 1  Assoc Metabolic Alkalosis  AG/ HCO 3 - < 1  Assoc N AG Met Acidosis Based on assumption that for each 1 meq/L increase in AG, HCO3 will fall by 1 meq/L

Slide 68:

However: Non HCO3 buffers esp intracellular buffers also contribute to buffering response on addition of H+. Becomes more pronounced as duration of acidosis increases. Hence  AG/ HCO 3 - > 1 even in absence of Met Alkalosis All added anions may not stay in EC comp and those that diffuse inside cells could lead to a lesser rise in AG than expected Hence  AG/ HCO 3 - < 1 even in states expected to have high AG Met Acidosis Salem et al, Arch Int Med 1992; 152: 1625-1629

Slide 69:

Strict use of AG to classify met acidosis & of AG/HCO3 to detect mixed/occult met acid-base disorders can be assoc with errors because of the possibility of change of AG by factors other than metabolic acid-base disturbances. Use of sequential AG determinations and observation of temporal profile of AG more imp than single value.

Modifications/Alternatives for AG:

Modifications/Alternatives for AG  AG/ HCO 3 - = 1-2  Pure High AG Met Acidosis  AG/ HCO 3 - > 2  Assoc Met Alkalosis  AG/ HCO 3 - < 1  Assoc N AG Met Acidosis Black RM. Intensive Care Medicine 2003; 852-864 Use of Corrected AG Corrected AG = Calculated AG + 2(Albumin gm/dL) + 0.5 (PO4 3 - mg/dL) Kellum JA et al. Chest 1996; 110: 18S



Slide 72:

1. HCO3 loss a. Renal b. GIT Decreased renal acid secretion – Increased production of non-volatile acids a. Ketoacids b. Lactate c. Poisons d. Exogenous acids Pathophysiology

Causes of High AG Met Acidosis:

Causes of High AG Met Acidosis Ketoacidosis: Diabetic Alcoholic Starvation Lactic Acidosis: Type A (Inadequate O2 Delivery to Cells) Type B (Inability of Cells to utilise O2) Type D (Abn bowel anatomy) Toxicity: Salicylates Paraldehyde Methanol Toluene Ethylene Glycol

Slide 74:

Renal Failure Rhabdomyolsis Causes of N AG Met Acidosis HCO3 loss: GIT Diarrhoea Pancreatic or biliary drainage Urinary diversions (ureterosigmoidostomy) Renal Proximal (type 2) RTA Ketoacidosis (during therapy) Post-chronic hypocapnia

Slide 75:

Impaired renal acid excretion: Distal (type 1) RTA Hyperkalemia (type 4) RTA Hypoaldosteronism Renal Failure Misc: Acid Administration (NH4Cl) Hyperalimentation (HCl containing AA sol) Cholestyramine Cl HCl therapy (Rx of severe met alkalosis) Black RM. Intensive Care Medicine 2003; 852-864

Manifestations of Met Acidosis:

Manifestations of Met Acidosis Cardiovascular Impaired cardiac contractility Arteriolar dilatation, venoconstriction, and centralization of blood volume Increased pul vascular resistance Fall in C.O., ABP & hepatic and renal BF Sensitization to reentrant arrhythmias & reduction in threshold of VFib Attenuation of cardiovascular responsiveness to catecholamines Adrogue et al, NEJM 1998; 338(1): 26-34

Slide 77:

Respiratory Hyperventilation  strength of respiratory muscles & muscle fatigue Dyspnea Metabolic Increased metabolic demands Insulin resistance Inhibition of anaerobic glycolysis Reduction in ATP synthesis Hyperkalemia ( secondary to cellular shifts) Increased protein degradation Cerebral Inhibition of metabolism and cell vol regulation M ental status changes (somnolence, o btundation & coma) Adrogue et al, NEJM 1998; 338(1): 26-34

Slide 78:

SERUM AG URINARY AG Total Urine Cations = Total Urine Anions Na + K + (NH4 and other UC) = Cl + UA (Na + K) + UC = Cl + UA (Na + K) – Cl = UA – UC (Na + K) – Cl = AG Helps to distinguish GI from renal causes of loss of HCO3 by estimating Urinary NH4+ (elevated in GI HCO3 loss but low in distal RTA). Hence a -ve UAG (av -20 meq/L) seen in former while +ve value (av +23 meq/L) seen in latter. Evaluation of Met Acidosis Kaehny WD. Manual of Nephrology 2000; 48-62

Slide 79:

PLASMA OSMOLAL GAP – Calc P Osm = 2 [Na+] + [Gluc]/18 + [BUN]/2.8 N Meas P Osm > Calc P Osm (upto 10 mOsm/kg) Meas P Osm - Calc P Osm > 15-20 mOsm/kg  presence of abn osmotically active substances (usually an alcohol) URINE OSMOLAL GAP - similar to P. Osm gap Calc U Osm = 2 [(Na+ u ) + (K+ u )] + [Gluc u ]/18 + [UUN]/2.8 Meas P Osm > Calc P Osm  excretion of NH4+ with non Cl- anion (e.g.hippurate) [ NH4+ u ] usually  50% of osmolal gap

Slide 80:

Met Acidosis N AG  AG Ketones +ve Serum Lactate  P Osm Gap (OH) B/AA = 5:1 (OH) B/AA = 3:1 +ve UAG - ve UAG Lactic Acidosis Intoxications DKA Alcoholic GIT RTA Ketoacidosis < 5.5 Urine pH  K  K > 5.5 Type 1 Type 2 Type 4 U Osm Gap Iatrogenic Acid Gain  N

Treatment of Met Acidosis:

Treatment of Met Acidosis Severe acidemia  Effect on Cardiac function most imp factor for pt survival since rarely lethal in absence of cardiac dysfunction. Contractile force of LV  as pH  from 7.4 to 7.2 However when pH < 7.2, profound reduction in cardiac function occurs and LV pressure falls by 15-30% Most recommendations favour use of base when pH < 7.15-7.2 or HCO3 < 8-10 meq/L. When to treat?

How to treat?:

How to treat? Rx Undelying Cause HCO3- Therapy Aim to bring up pH to 7.2 & HCO3-  10 meq/L Qty of HCO3 admn calculated: 0.5 x LBW (kg) x HCO3 Deficity (meq/L) Vd of HCO3 50% in N adults. However in severe met acidosis can  to 70-80% in view of intracellular shift of H+ and buffering of H+ by bone and cellular buffers.

Why not to treat?:

Why not to treat? Considered cornerstone of therapy of severe acidemia for >100 yrs Based on assumption that HCO3- admn would normalize ECF & ICF pH and reverse deleterious effects of acidemia on organ function However later studies contradicted above observations and showed little or no benefit from rapid and complete/over correction of acidemia with HCO3.

Adverse Effects of HCO3- Therapy :

Adverse Effects of HCO3- Therapy  CO2 production from HCO3 decomposition  Hypercarbia (V>A) esp when pul ventilation impaired Myocardial Hypercarbia  Myocardial acidosis Impaired myocardial contractility &  C.O.  SVR and Cor A perfusion pressure  Myocardial Ischemia esp in pts with HF Hypernatremia & Hyperosmolarity  Vol expansion  Fluid overload esp in pts with HF Intracellular (paradoxical) acidosis esp in liver & CNS ( CSF CO2)

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 gut lactate production,  hepatic lactate extraction and thus  S. lactate  ionized Ca  VO2,  PaO2,  P 50 O2 CORRECTION OF ACIDEMIA WITH OTHER BUFFERS: Carbicarb - not been studied extensively in humans - used in Rx of met acidosis after cardiac arrest and during surgery - data on efficacy limited


THAM THAM (Trometamol/Tris-(OH)-CH3-NH2-CH3) - biologically inert amino alcohol of low toxicity. Capacity to buffer CO2 & acids in vivo as well as in vitro pK at 37 C = 7.8 (HCO3 has pK of 6.1) More effective buffer in physiological range of blood pH Accepts H+/CO2 and generates HCO3/  PaCO2 R-NH2 + H2O + CO2  R-NH3 + + HCO3 - R-NH2 + H + + La -  R-NH3 + + La -

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Rapidly distributed in ECF except RBCs & liver cells --> excreted by kidneys in the protonated form (NH3+) Effective as buffer in closed or semiclosed system (unlike HCO3- which req an open system to eliminate CO2) Effective in states of hypothermia Side Effects: 1. Tissue irritation and venous thrombosis if admn through peripheral vein - seen withTHAM base (pH = 10.4) THAM acetate (pH = 8.6) well tolerated - does not cause tissue or venous irritation

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2. Large doses can cause resp depression 3. Hypoglycemia Initial loading dose of THAM acetate (0.3 ml/L sol) calculated: Lean BW (kg) x Base Deficit (meq/L) Max daily dose ~15 mmol/kg Use in severe acidemia (pH < 7.2): 1. Resp failure: a) Induced Acute Hypercapia - Apnoeic oxygenation during bronchoscopy and organ collection from organ donors b) ARDS with permissive hypercapnia

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c) Acute Severe Asthma with severe respiratory acidosis 2. DKA 3. Renal failue 4. Salicylate or Barbiturate intoxication 5. Raised ICT due to cerebral trauma 6 Cardioplegia during Open heart surgery 7. CPR (after restoration of cardiac function) 8. During liver transplantation 7. Chemolysis of renal calculi 8. Severe burns Nahas et al, Drugs 1998; 55(2):191-224




Introduction Met alkalosis common (upto 50% of all disorders) Severe met alkalosis assoc with significant mortality Arterial Blood pH of 7.55  M ortality rate of 45% Arterial Blood pH of 7.65  M ortality rate of 80% (Anderson et al. South Med J 80: 729–733, 1987) Metabolic alkalosis has been classified by the response to therapy or underlying pathophysiology

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1. INITIATING EVENT a. HCO3- gain b. H+ loss 1) Renal 2) GIT c. H+ shift d. Contraction/chloride depletion Pathophysiology

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2. MAINTENANCE Alkaline loads generally excreted quickly and easily by the kidney. Significant metabolic alkalosis can thus only occur in the setting of impaired HCO3- excretion Causes of impaired HCO3- excretion 1) Decreased GFR – volume depletion 2) Increased reabsorption – volume/chloride depletion hyperaldosteronism

Pathophysiological Classification of Causes of Metabolic Alkalosis:

Pathophysiological Classification of Causes of Metabolic Alkalosis H+ loss: GIT Chloride Losing Diarrhoeal Diseases Removal of Gastric Secretions (Vomitting, NG suction) Renal Diuretics (Loop/Thiazide) Mineralocorticoid excess Post-chronic hypercapnia Hypercalcemia High dose i/v penicillin Bartter’s syndrome Black RM. Intensive Care Medicine 2003; 852-864

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HCO3- Retention: Massive Blood Transfusion Ingestion (Milk-Alkali Syndrome) Admn of large amounts of HCO3- Contraction alkalosis Diuretics Loss of high Cl-/low HCO3- GI secretions (vomitting and some diarrhoeal states) H+ movement into cells Hypokalemia Refeeding Black RM. Intensive Care Medicine 2003; 852-864

Classification of Causes of Metabolic Alkalosis acc to response to therapy:

Classification of Causes of Metabolic Alkalosis acc to response to therapy VOLUME/SALINE RESPONIVE (Vol/Cl- Depletion) Gastric losses: vomiting, mechanical drainage, bulimia, gastrocystoplasty Chloruretic diuretics: bumetanide, chlorothiazide, metolazone etc. Diarrheal states: villous adenoma, congenital chloridorrhea Posthypercapneic state Dietary chloride deprivation with base loading: chloride deficient infant formulas Cystic fibrosis (high sweat chloride) Gall JH. J Am Soc Nephrol 2000; 11: 369–375.

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VOLUME REPLETE/SALINE UNRESPONIVE K+ DEPLETION/MINERALOCORTICOID EXCESS Primary aldosteronism: Adenoma Renin-responsive Idiopathic Glucocorticoid-suppressible Hyperplasia Carcinoma Apparent mineralocorticoid excess: Primary deoxycorticosterone excess: 11  - & 17 - hydroxylase deficiencies Drugs: licorice (glycyrrhizic acid) as a confection or flavoring, carbenoxolone Liddle syndrome Gall JH. J Am Soc Nephrol 2000; 11: 369–375.

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Secondary aldosteronism Adrenal corticosteroid excess: Severe hypertension: malignant/accelerated renovascular Hemangiopericytoma, nephroblastoma, RCC Bartter and Gitelman syndromes and their variants Laxative Abuse, Clay Ingestion HYPERCALCEMIC STATES ( HCO3- reabsorption) Hypercalcemia of malignancy primary secondary exogenous Gall JH. J Am Soc Nephrol 2000; 11: 369–375.

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Ac or Ch milk-alkali syndrome (both HCO3- & Ca ingested  additional mechanisms for alkalosis incl vomiting &  GFR MISC Carbenicillin/ampicillin/penicillin. HCO3- ingestion: massive or with renal insufficiency Recovery from starvation Hypoalbuminemia (Alkalosis usually mild and due to diminution of -ve charge normally contributed by albumin towards AG & shift in buffering curve for plasma). Gall JH. J Am Soc Nephrol 2000; 11: 369–375.

Manifestations of Met Alkalosis:

Manifestations of Met Alkalosis Symp of met alkalosis per se difficult to separate from those of Cl-/K+/Vol depletion  latter usually more apparent than those directly attributable to alkalosis. Cardiovascular Arteriolar constriction Reduction in Coronary BF/Anginal threshold Predisposition to refractory SV & V arrhythmias (esp if pH > 7.6) Respiratory - Hypoventilation ( Compensatory)  Hypercapnia/Hypoxemia Adrogue et al, NEJM 1998; 338(2): 107-111

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Metabolic Stimulation of anaerobic glycolysis & organic acid production Reduction plasma ionized Calcium conc Hypokalemia ( secondary to cellular shifts) Hypomagnesemia & Hypophosphatemia Cerebral Reduction in Cerebral BF  m ental status changes (stupor, lethargy & delirium) N-M irritability (related to low ionized plasma Ca)  Tetany, Hyperreflexia, Seizures Adrogue et al, NEJM 1998; 338(2): 107-111

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Urinary Cl- & K+ measurements before therapy useful diagnostically. Low urinary chloride (<10 mEq/L) seen in alkalotic states where Cl- depletion predominates (except cause is use of chloruretic diuretic)  Remains low until Cl- repletion nearly complete. Urinary K+ conc of >30 mEq/L with  S. K+ suggests renal K+ wasting due to: Intrinsic renal defect Diuretics High circulating aldosterone Urinary K+ conc of <20 mEq/L with  S. K+ suggests extrarenal K+ loss. Evaluation of Met Alkalosis

Treatment of Metabolic Alkalosis:

Treatment of Metabolic Alkalosis Although relationship between alkalemia and mortality not proven to be causal, severe alkalosis should be viewed with concern, and correction by the appropriate intervention should be undertaken when the arterial blood pH exceeds 7.55 Imm goal of therapy is moderation & not full correction of the alkalemia. Reducing plasma HCO3- to <40 meq/L short-term goal, since the corresponding pH  7.55 or lower. Most severe metabolic alkalosis is of Cl- responsive type

Treatment of Vol Depleted/Saline Responsive Metabolic Alkalosis:

Treatment of Vol Depleted/Saline Responsive Metabolic Alkalosis Rx underlying cause resp for vol/Cl- depletion While replacing Cl- deficit, selection of accompanying cation (Na/K/H) dependent on: Assessment of ECF vol status Presence & degree of associated K depletion, Presence, degree & reversibility of  of GFR. Pts with vol depletion usually require replacement of both NaCl & KCl.

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DEPLETION OF BOTH CL- & ECF VOL (most common): Isotonic NaCl appropriate therapy  simultaneously corrects both deficits. In patients with overt signs of vol contraction, admn of min of 3 - 5 L of 150 mEq/L NaCl usually reqd to correct vol deficits & metabolic alkalosis. When ECF vol is assessed as normal, total body Cl- deficit can be estimated as: 0.2 x BW (kg) x Desired [ Cl- ] – Measured [ Cl- ] (mEq/L) Replace continuing losses of fluid & electrolytes Correction of Na, K & Cl deficits & assoc prerenal azotemia promotes HCO3 excretion and alkaline diuresis with a  in plasma HCO3 towards normal.

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DEPLETION OF CL- &  ECF VOL Admn of NaCl is inadvisable for obvious reasons. Chloride should be repleted as KCl unless hyperkalemia present or concomitant  GFR where ability to excrete K+ load is hampered. Administration of acetazolamide accelerates bicarbonaturia esp: If natriuresis with a high Na excretion rate req simultaneously If high serum K+ present Monitoring needed to detect associated kaliuresis and phosphaturia. GFR must be adequate (C/I if S. creat >4 mg/dl)

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CL- DEPLETION with  ECF VOL & HYPERKALEMIA (Use of NaCl/KCl C/I) Hydrochloric Acid I/v HCl indicated if correction reqd imm Amount of HCl given as 0.1 or 0.2 M sol needed to correct alkalosis estimated as: 0.5 x BW (kg) x Desired [ Cl- ] – Measured [ Cl- ] (mEq/L) Continuing losses must also be replaced. Use of 50% of BW as V d of infused protons done so that infused protons act to correct alkalosis in both ICF and ECF & restore buffers at both sites ½ correction given since imm goal of therapy is correction of severe & not full correction of alkalemia.

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HCl has sclerosing properties  must be admn through a central venous catheter (placement confirmed radiologically to prevent leakage of HCl  sloughing of perivascular tissue) Infusion rates N < 0.2 mmol/kg BW/hr with m ax rate of 25 mEq/h. HCl can also be infused after adding it to AA sol, fat emulsion or dextrose sol containing electrolytes & vit without causing adverse chemical RX - can also be admn through a peripheral vein Req frequent measurement of ABG and electrolytes. Ammonium Chloride Can be given into a peripheral vein Rate of infusion should not exceed 300 mEq/24 h. C/I in presence of renal or hepatic insufficiency (worsening of azotemia & ppt of acute ammonia intoxication with coma respectively).

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Dialysis In presence of renal failure or severe fluid overload state in CHF, dialysis +/- UF may be reqd to exchange HCO3 for Cl & correct metabolic alkalosis. Usual dialysates for both HD/PD contain high [H CO3- ] or its metabolic precursors & their conc must be reduced. In pts with unstable hemodynamics, CAVH/CVVH using NaCl as replacement sol can be done. Adjunct Therapy PPI can be admn to  gastric acid production in cases of Cl-depletion met alkalosis resulting from loss of gastric H+/Cl- (e.g. pernicious vomiting, req for continual removal of gastric secretions, gastrocystoplasty Met alkalosis likely to persist & replacement of preexisting deficits hampered by ongoing losses

Treatment of Vol Replete/Saline Unresponsive Metabolic Alkalosis:

Treatment of Vol Replete/Saline Unresponsive Metabolic Alkalosis MINERALOCORTICOID EXCESS Therapy should be directed at either removal of the source or its blockade. K-sparing diuretics, esp spironolactone helpful in reversing adverse effects of mineralocorticoid excess on Na, K and HCO3excretion. Restriction of Na and addition of K to diet also helpful both in Rx of alkalosis as well as HTN. Correction of K deficit reverses alkalinizing effects but elimination of aldosterone excess essential to achieve permanent correction.

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MILK-ALKALI SYNDROME & OTHER HYPERCALCEMIC STATES Cessation of alkali ingestion & Ca sources (often milk and calcium carbonate) Treatment of underlying cause of hypercalcemia Cl- and Vol repletion for commonly associated vomiting

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