02. Acid/Base Disorders

References: Marino ICU Chapter 28, Sabiston Chapter 81-90, Acid-Base Handout

Acid base hemostasis is necessary for normal physiologic function

-Contractile protein function - myocardial arrhythmias, poor cardiac output

-Enzyme function - imidazole potion of histidine amino acids which bind protons

-Clotting factor function - triad of death in trauma patients (metabolic acidosis, coagulopathy, hypothermia)

Definitions:

-Acid - H⁺ donor, Base - H⁺ acceptor

-Acid-base status is reflected by H⁺ concentration (normal [H⁺] = 40 neq/L)

-[H⁺] expressed as pH = -log([H⁺]) (inverse relationship between pH and [H⁺])

-Acidosis: pH < 7.35, Alkalosis: pH > 7.45

Volatile Acids (Mostly Carbonic Acid: H₂CO₃)

-15-20,000 meq/day of CO₂ produced by metabolism - hydrated to Carbonic Acid

-Volatile = can be re-equilibrated to CO₂ in lungs and ventilated off

-CO₂ + H₂O <--> H₂CO₃ <--> H⁺ + HCO₃^-

-Uncharged (easily diffusable)<--><--> charged (requires energy to move across membranes)

Nonvolatile Acids (Total cocnentration expressed as A_TOT)

-Cannot be breathed off

-50-100 meq/day, often considered negligible compared to carbonic acid

-Sulfuric Acid (H₂SO₄), Phosphoric Acid (H₃PO₄), Albumin

Determination of systemic pH

-Assuming A_TOT within normal range - balance between CO₂ and HCO₃^- state determines pH

-This relationship is described by the Henderson-Hasselbach equation

pH = 6.1 + log[HCO₃^-] / (0.03 x PaCO₂)

-As well as the Henderson equation

[H⁺] = 24 x PaCO₂ / [HCO₃^-]

-These two equations just mean the concentration of acid (pH, [H⁺]) is directly related to the partial pressure of CO₂ and inversely related to the concentration of HCO₃^-

-In reaction to a change in CO₂ or HCO₃^- the body will attempt to change the other to compensate and maintain pH, maintain acid-base homeostasis

Acid-Base Disorders --> compensatory changes

-Respiratory acidosis (hypoventilation) - increased PCO₂ --> increased HCO₃

-Respiratory alkalosis (hyperventilation) - decreased PCO₂ --> decreased HCO₃

-Metabolic acidosis - decreased PCO₂ --> decreased HCO₃

-Metabolic alkalosis - increased PCO₂ --> Increased HCO₃

Acid-Base Regulation

Buffers - immediately (to minutes)

-Extracellularly: 400 mmol buffering capacity

HCO3- and carbonic acid (95%) - vast majority of ECF buffering

Organic phosphates (5%)

-Intracellularly: 800 mmol buffering capacity

HCO3- and carbonic acid (42%)

Bone

Inorganic phosphates (6%)

Proteins (52%) - especially histadine amino acid proteins

Respiratory Compensation - minutes to hours

-Hypercapnia, hypoxia and acidosis stimulate increased depth and rate of respiratory via chemorecptors (central and carotid body), without these stimuli, breathing slows down

-Blows off CO₂ and works in conjunction with HCO₃

-Patients can become exhausted from hyperventilation and crash - need to be ventilated

-If outside expected range = mixed acid/base disorder

Compensation for Metabolic Acidosis: Expected PaCO₂ = 1.5 x HCO₃ + (8 +/- 2)

Compensation for Metabolic Alkalosis: Expected PaCO₂ = 0.7 x HCO₃ + (21 +/- 2)

-Often have to hyperventilate surgical patients with lactic acidosis to prevent systemic effects of low pH

Renal compensation - hours, but not complete till days

-Renal compensation by excretion (Alkalosis) or reabsorption (Acidosis) of HCO₃

Slower but most powerful mechanism of compensation

Begins within 6-12 hours of PaCO₂ alteration, fully developed after 48 hours

Re-absorption of all HCO₃ with levels PaCO₂ < 27

Reabsorption limited by HCO₃ concentration

Carbonic anhydrase processes HCO3 for excretion intracellularly in kidney

-Renal compensation by H+ secretion

Means of eliminating non-volatile acids

Main mechanism - Ammonium ion - normally 30-50 meq/day of H⁺ is excreted as NH₄⁺, can increase over several days up to 250 meq/day with metabolic acidosis

Titratable Acid (main eg: Phosphoric acid Na₂HPO₄) - can excrete 10-40 meq/day of H⁺

-In severe renal failure, unable to excrete excess protons from diet and acidosis develops

-Cannot fully compensate or over compensate, if pH outside expected range = mixed abnormality

Acute Respiratory Acidosis: Expected pH = 7.40 - [0.008 x (PaCO₂ - 40)]

Acute Respiratory Alkalosis: Expected pH = 7.40 + [0.008 x (40 - PaCO₂)]

Chronic Respiratory Acidosis (~48hrs): Expected pH = 7.40 - [0.003 x (40 - PaCO₂)]

Chronic Respiratory Alkalosis (~48hrs): Expected pH = 7.40 + [0.003 x (40 - PaCO₂)]

*For acute, add 0.08 for every 10 PaCO₂, for chronic, add 0.03 for every 10 PaCO₂

Metabolic acidosis

Anion Gap

Electrochemical balance: total anions=total cations

Na + unmeasured cations = Cl + HCO3 + unmeasured anions

Na - Cl - HCO3 = unmeasured anions - unmeasured cations = anion gap

-Normal anion gap = 8-12

Unmeasured anions:

-Albumin (15 meq/L) - must correct for hypoalbuminemia

corrected AG = measured AG + 2.5 (4.5 - Albumin)

-Organic Acids (5 meq/L)

-Phosphate (2 meq/L)

-Sulfate (1 meq/L)

-Total unmeasured anions (23 meq/L)- mostly due to albumin

Unmeasured cations:

-Ca++ (5 meq/L)

-K+ (4.5 meq/L)

-Mg++ (1.5 meq/L)

-Total unmeasured cations (11 meq/L)

The Gap-Gap

-If the acid/base disorder is a simple high AG metabolic acidosis, then the change in the gap should equal the change in HCO₃ (26-gap elevation~HCO₃)

-If HCO3 is higher - concurrent metabolic alkalosis

-If HCO3 is lower - concurrent metabolic acidosis

Acid-Base Analysis

1. Ensure data are valid

2. Know normal values (pH 7.35-7.45, PaCO₂ 35-45, HCO₃ 24-28, AG 8-12)

3. pH - Acidosis or Alkalosis?

4. HCO₃, PaCO₂ - Primary metabolic or respiratory?

5. Approprate compensation or additional disturbance?

6. Check Anion Gap

7. Correct anion gap for hypoalbuminemia

8. +/- check gap-gap with high anion gap acidosis

Stewart Methodology

-Limitations to traditional acid-base methodology

-Emphasized importance of ion movement across membranes and effects on pH

-Very complex, requires program to do acid base analysis - not easy to implement, no proven clinical benefit

Importance of ion charges

Addition of anions ----> acidifying effect

-Anion addition --> excessive negative charge --> decreased HCO3 re-absorption --> charge neutrality

Addition of cations ----> alkalinizing effect

-Cation addition --> excessive positive charge --> increased HCO3 re-absorption --> charge neutrality

Normal saline has 154meq/L of Na⁺ and 154 meq/L of Cl^-

Plasma has 135-145 meq/L of Na⁺ and 101-111 meq/L of Cl^-

NS gives excess Cl^- and can result in hyperchloremic, normal AG metabolic acidosis

Treatment: D5W + 2 or 3 amps of NaHCO₃ (1 amp NaHCO₃ = 54 meq)

(fixed cation with labile anion)

LR contains 130 meq/L Na⁺, 109 meq/L Cl^-

Results in increased cations and therefore alkanizing effect - despite 28 mmol lactate since this is quickly metabolized to HCO₃ unlike large amounts that build up by hypoperfusion etc.

Not contraindicated in lactic acidosis, actually may be better than NS since it is alkalinizing

Acidosis shifts oxyhemoglobin curve to the right - releases O2 easier (better than alkalosis)

Alkalosis shifts oxyhemoglobin curve to the left - won't release O2 (worse than acidosis)

Metabolic Acidosis

High anion gap - reflects an increase in non-volatile acids

-Lactic acidosis (most common in surgical patients, part of deathly triad with hypotension and coagulopathy)

poor perfusion, lack of oxygen to receive electons, anaerobic metabolism, buildup of lactate, inefficient

Treatment is resuscitation - Aggressive fluid resuscitation (LR is best), blood if needed, treat sepsis, stop bleeding, intubate to increase ventilation if necessary

Bicarbonate does not help - only consider if pH < 7.15 due to impaired cardiac contractility, no can be problematic:

Post-recovery metabolic alkalosis

Hypernatremia

CO2 "backed up in venous system

Calcium binding

No evidence of benefit during CPR

-Ketoacidosis

DM - protocols w/ fluid, potassium replacement, insulin

Alcohol - reduced nutrient intake (increases ketone production), hepatic oxidation of ethanol (generates NADH, enhancing b-OHB) and dehydration (reduces urinary ketone excretion), in addition thiamine deficiency - pyruvate dehydrogenase cofactor - increases ketones

-ESRD

-Toxin ingestion

Methanol, ethylene glycol, EtOH, salicylates, metformin (Profound; common after CT w/contrast; treat with bicarbonate - only one)

-D-lactate acidosis - Jejuno-ileal bypass (no longer performed) or Short bowel syndrome

Decreased ability to process carbohydrates --> excess glucose and startch in the colon --> D-Lactate formation in colon (bacteria) --> systemic absorption and D-lactic acidosis

Slow to clear (L-lactic dehydrogenase can't recognize)

SXS: Neuro: confusion, ataxia, slurred speech, memory loss (similar to EtOH intoxication)

Labs show increased AG metabolic acidosis with normal lactate (D-lactate not recognized by L-lactate assay)

Treat: HCO3, Abx, low carb diet

-Rare complication of malignancies

Normal Anion Gap - reflects a decrease in HCO₃

-Diarrhea - loss of HCO3 in stool

-Fistulas - direct HCO3 loss

-Saline Infusion - loss of HCO3 in urine

-Early Renal Failure - Loss of HCO3 in urine

-Renal Tubular Acidosis - loss of HCO3 in urine

-Acetazolamide - loss of HCO3 in urine (counteract furosemide metabolic alkalosis)

-Ureteroenterostomy - loss of HCO3 in stool

Normal anion gap metabolic acidosis treatment - treat the underlying cause, NaHCO3 prn (unlike high anion gap)

Metabolic Alkalosis

Chloride Responsive

-GI losses - Vomiting, NG suction, Cl- wasting (sometimes diarrhea)

-Diuretic therapy - furosemide (very common)

-PCN effect

-Post hypercapnia - takes longer for chronic renal compensation to react

-Contraction alkalosis - loss of significant volumes of HCO3 - free fluid - eg. overdiuresis, ng losses, sweat losses in CF,

treat: volume (NS best), K+ and Cl- replacement

Chloride Unresponsive

-Adrenal Hyperfunction - Conn's syndrome, cushing's syndrome - aldosterone increases sodium reabsorption and hydrogen excretion

-Exogenous steroids

-Re-feeding syndrome - low mg low phos

-Alkali Intake/administration

-Hypercalcemia

-Milk-alkali syndrome

Alkalosis treatments

-Acetazolamide (diamox) - carbonic anhydrase inhibitor - makes you acidotic

-HCl

Hypokalemia and metabolic alkalosis

-transcellular cation exchange - low potassium causes hydrogen excretion

-H-K ATPase in distal convoluted tubule,

-decreased Cl- resorption

Respiratory acidosis

-Respiratory failure - CNS depression, neuromuscular disorders, thoracic cage limitations, restrictive lung abnormalities, obstructive lung disease, ventilator malfunction

-Treat: mechanical ventilation

Respiratory alkalosis

-Can be seen initial abnormality in sepsis

-CNS disorders, med effects, sepsis, hyperthyroidism, pregnancy, liver failure

ABG vs. VBG

-correlate well with PaCO2, pH, HCO3

-Cannot substitute quantitatively

8 STEPS TO COMPLETE ACID/BASE ANALYSIS

1. Utilize pCO2 and pH data from ABG but obtain HCO3 (CO2) from Chem panel as the HCO3 on ABG is a calculated value. Draws need to occur concurrently.

Ensure data is valid: 24 (pCO2) / (HCO3) then place 10-9, then take log, should ~ pH

If it doesn't there is a discrepancy and lab redraw should be considered.

2. Know normal values:

pH 7.35 - 7.45

PaCO2 = 35 - 45

HCO3 = 24 - 28

3. Acidosis or Alkalosis? - even if pH is normal, technically should go through remaining steps to rule out mixed picture

4. Metabolic or respiratory?

5. Appropriate compensation or 2nd disturbance?

Metabolic acidosis: Expected PaCO2 = 1.5 (HCO3) + 8 (+/-2)

Metabolic alkalosis: Expected PaCO2 = 0.7 (HCO3) + 21 (+/- 2)

Acute respiratory acidosis: Expected pH = 7.40 - 0.008 (PaCO2 - 40)

Chronic respiratory acidosis: Expected pH = 7.40 - 0.003 (PaCO2 - 40)

Acute respiratory alkalosis: Expected pH = 7.40+ 0.008 (40 - PaCO2)

Chronic respiratory alkalosis: Expected pH = 7.40 + 0.003 (40- PaCO2)

Acute = under 24-48 hrs

6. Determine anion gap = Na - (Cl + HCO3)

7. Correct anion gap for hypoalbuminemia: AGc = AGm + 2.5 ( 4.5 - albumin)

8. With elevated anion gap cases check for appropriate HCO3:

26-gap elevation should approximate HCO3

If not, metabolic disturbance is present