Surgical Foundations: Wednesday, November 3, 2010
Harry Kim, Dan Charleton, Dan Hoppe, and Xian Kang
Royal College Objectives
• Understand the physiologic basis for fluid, electrolyte, and acid‐
base management of the surgical patient, including body water compartments: composition, osmotic activity and oncotic pressure of body fluids; water and electrolyte exchange; mechanisms of osmoregulation and volume regulation; buffer systems and mechanisms of acid‐base homeostasis
• Diagnose and prescribe appropriate treatment for fluid, electrolyte, and acid‐base disturbances, on the basis of clinical manifestations and interpretation of blood gases and serum and urine biochemistry, including metabolic acidosis and alkalosis, respiratory acidosis and alkalosis, mixed acid‐base disturbances, hyponatremia, hypernatremia, syndrome of inappropriate ADH release, diabetes insipidus
Hydrogen Ion
Almost all enzyme systems are influenced by the hydrogen ion
+
pH and H
Minute hydrogen ion concentration in the body
pH inversely related to H+ concentration
pH = log 1/[H+] = ‐ log [H+]
Normal pH
Compatibility of life
Arterial blood = 7.4
Lower limit pH = 6.8
Venous blood and interstitial fluid = 7.35
Upper limit pH = 8.0
Acids & Bases
Acid
• Molecules containing hydrogen atoms that can release hydrogen ions in solution
• Acidosis : excess addition of H+ to body fluids
Base
• Ion or molecule that can accept a hydrogen ion
• Alkalosis : excess removal of H+ from body fluids
Hydrogen Ion Balance
Regulate [H+] & prevent acidosis and/or alkalosis
⇔
Chemical Acid‐Base Buffer
⇔
• Combines with acid or base to prevent excessive changes in H+
concentration
• Does not eliminate H+ from or add them to body
• Buffer = any substance that can reversibly bind H+
• Reacts within a fraction of a second
Bicarbonate Buffer System
* carbonic anhydrase
Lung alveoli & epithelial cells of Renal Tubules
Bicarbonate salt occurs as sodium bicarbonate (NaHCO3) in ECF
Weak dissociation of H2CO3
Henderson‐Hasselbalch Equation
• Physiologic acid‐base homeostasis results from coordination of lungs and kidneys
• Acid‐base disorders occur when lungs and/or kidneys are impaired
• Makes bicarbonate buffer system the most powerful extracellular buffer in the body due to precise regulations of HCO3‐ and CO2 by kidneys and lungs
• Other buffer systems: phosphate, ammonia, proteins
Respiratory
Metabolic
Acidosis
↑ PCO2 ↓ HCO3‐
Alkalosis
↓ PCO2
↑ HCO3‐
Respiratory Regulation
• Controls ECF CO2 concentration via lungs
• Changes in pulmonary ventilation OR rate of CO2 formation by tissues affects ECF PCO2
• [H+] affects rate of alveolar ventilation
• Effectiveness between 50‐75%
• Response time of 3‐12 minutes
• Physiologic buffer system – provides time for kidneys to eliminate the imbalance
• Overall buffering power 1‐2X as great as the buffering power of all other chemical buffers in the ECF combined
Renal Regulation
• HCO3‐ filtered into tubules
• H+ secreted into tubular lumen by tubular epithelial cells
• Both reabsorption of HCO3‐ and excretion of H+
accomplished through process of H+ secretion by tubules
• HCO3‐ reacts with secreted H+ to form H2CO3 before being reabsorbed
• for each HCO3‐ reabsorbed, an H+ must be secreted
•Alkalosis – fail to reabsorb all filtered bicarbonate Æ
increased excretion of bicarbonate
•Acidosis – reabsorption of all filtered bicarbonate and formation of new bicarbonate
• Renal regulation:
• secretion of H+ • reabsorption of filtered HCO3‐
• production of new HCO3‐
Renal Regulation
• H+ ion secretion and HCO3‐ reabsorption occurs in all parts of tubules except descending and ascending thin limbs of loop of Henle
• 80‐90% of reabsorption/excretion occurs in proximal tubules; 10% in thick ascending loop of Henle
• HCO3‐ : H+ ratio
• acidosis/alkalosis correction via kidneys based on incomplete titration
• Volatile vs. Non‐volatile acids
• binds free excess H+ to combine w/ other urinary buffers
• H+ + non‐volatile acid = new HCO3‐
added to blood
• ie. phosphate, ammonia
Acidosis Correction
• Metabolic • Decreased filtration of HCO3‐ b/c decreased ECF [HCO3‐]
• Excess H+ over HCO3‐
• Compensation: • Increased ventilation rate Æ reduces PCO2
• Renal compensation Æ addition of new bicarbonate to ECF w/ excess H+
• Respiratory
• Increased PCO2 = increased ECF [H+] Æ decreased pH
• Compensation:
• Increased plasma HCO3‐ via addition of new bicarbonate to ECF by kidneys
Alkalosis Correction
• Excess HCO3‐ can’t be reabsorbed from tubules without H+ Æ excretion in urine
• Respiratory
• Decrease in plasma CO2 caused by hyperventilation
• Reduced PCO2 causes less H+ secretion by renal tubules Æ balance of HCO3‐ > H+
• Thus: HCO3‐ that doesn’t react with H+ becomes excreted
• Metabolic
• Increased ECF HCO3‐ concentration
• Part compensation via reduced respiration rate Æ increases PCO2
• Increased HCO3‐ concentration in ECF causes increased filtered load of HCO3‐ Æ
balance of HCO3‐ > H+ in renal tubular fluid
• Excess HCO3‐ fails to be reabsorbed Æ urinary excretion
Arterial Blood Gas Interpretation
Interpretation of ABGs
pH
• Measurement of acidity or alkalinity, based on the hydrogen (H+) ions present.
• The normal range is 7.35 to 7.45
PaO2
• The partial pressure of oxygen that is dissolved in arterial blood.
• The desired range is 80 to 100 mm Hg
• Will vary greatly based on inspired FiO2
PaCO2
• The amount of carbon dioxide dissolved in arterial blood.
• The normal range is 35 to 45 mm Hg
Interpretation of ABGs
HCO3
• The calculated value of the amount of bicarbonate in the bloodstream.
• The normal range is 22 to 26 mEq/liter
(others)
SaO2
• The arterial oxygen saturation.
• The normal range is 95% to 100%.
Base Excess
• The base excess indicates the amount of excess or insufficient level of bicarbonate in the
• system.
• The normal range is –2 to +2 mEq/liter.
• (A negative base excess indicates a base deficit in the blood.)
1. What is the primary disorder?
2. What is the compensation?
•
Is this a mixed disorder?
3. If metabolic acidosis… what are
the “gaps”?
Determine Primary Disorder
1) Look at pH
• Acidemia or Alkalemia?
• <7.35 or >7.45?
•*If normal, may be a mixed disorder
Determine Primary Disorder
2) Look at pCO2
• For a primary respiratory disorder, pH and pCO2 are inversely related
Therefore:
• pH < 7.35 and pCO2 > 45 mmHg = respiratory acidosis
• pH > 7.45 and pCO2 < 35 mmHg = respiratory alkalosis
If pH and pCO2 moving in same direction:
Suspect primary metabolic disorder
Determine Primary Disorder
3) Look at HCO3‐
• For a primary metabolic disorder, pH and HCO3‐ will move in the same direction
• Therefore:
• pH <7.35 and HCO3 <22 = metabolic acidosis
• pH >7.45 and HCO3 >26 = metabolic alkalosis
•pCO2 will also move in the same direction
Determine Compensation
Primary Disorder
Change in pCO2 (mmHg)
Change in HCO3‐
(mEq/L)
Acute Respiratory Acidosis ↑ 10
↑1
Chronic Respiratory Acidosis
↑10
↑3.5
Acute Respiratory Alkalosis
↓10
↓2
Chronic Respiratory Alkalosis
↓10
↓5
Compensatory
met. alkalosis
Compensatory
met. acidosis
Determine Compensation
Change in HCO3‐
(mEq/L)
Change in pCO2 (mmHg)
Metabolic
Acidosis ↓1
↓1.0‐1.5
Compensatory
resp. alkalosis
Metabolic
Alkalosis
↑1
↑0.5‐1.0
Compensatory
resp. acidosis
Primary Disorder
Based on Winter’s Formula:
•Expected pCO2 = [(1.5 x HCO3) +8] ±2
•Compare with measured to determine compensation
Mixed Disorders
• Suspect a “mixed” disorder, i.e. a second primary disorder, if:
• Compensation is inappropriate
• Normal pH but abnormal pCO2 and HCO3‐
• pCO2 and HCO3‐ change in opposite directions
Examples:
pH 7.27, pCO2 60, HCO3‐ 17
pH 7.40, pCO2 30, HCO3‐ 20
Metabolic Acidosis: Anion Gap
• Anion gap = (Na+ + K+) ‐ [Cl‐ + HCO3‐]
• K+ typically omitted in daily practice
• Normal range of 12 +/‐ 2
• An increase implies the presence of unmeasured anions in the serum • A normal AG acidosis implies loss of HCO3
• (aka hyperchloremic metabolic acidosis)
*NOTE* For each Albumin ↓10g/L, add 3 to calculated AG, since loss of albumin with artificially increase serum anion concentrations
Metabolic Acidosis : Osmolar Gap
• Check in AG acidosis, especially if etiology unclear
• Calculated osmolality = 2 x [Na] + [glucose] + [urea]
• Aka “Two salts and a sticky BUN”
• OG = measured serum osmolality − calculated osmolality
• A normal osmolar gap is < 10
• Elevated osmolar gap implies unmeasured osmoles, namely toxic alcohols
Metabolic Acidosis: Delta Gap
• ΔAG = change in AG from normal range
• ΔHCO3 = change in bicarb from normal range
• Delta gap = ΔAG ‐ ΔHCO3
• Delta gap is the amount that bicarb should be ↓ due to unmeasured cations
• Measured HCO3 + Delta Gap should fall in normal range of Bicarb
• If <22 there is less “corrected bicarb” than expected, therefore there is a concurrent non‐AG metabolic acidosis
• If >26 there is more than expected, and there is a concurrent metabolic alkalosis
Example:
AG = 20, HCO3 = 9 Å “should be” 14
Summary
1. What is the primary disorder?
2. Is the compensation appropriate?
• If not appropriate, what is other primary disorder
3. If metabolic acidosis… what is the AG?
• AG vs. hyperchloremic acidosis
4. If AG elevated… • What is the osmolar gap?
• If elevated then suspect presence of toxic alcohols
• What is the delta gap?
• If elevated then metabolic alkalosis present, if decreased then non‐
AG acidosis also present
Elevated Anion Gap
• An elevated anion gap is caused by the addition of a fixed acid to the ECF
• Acids added to ECF dissociate into H+ and A‐
• The H+ combine with bicarb to form carbonic acid, which decreases ECF bicarb and elevates the anion gap
• Usual causes of elevated AG metabolic acidosis are:
• Lactic acidosis
• Ketoacidosis
Elevated Anion Gap
• More comprehensive list:
M‐ methanol
U‐ uremia (impaired secretion of H+ into distal tubules)
D‐ diabetic ketoacidosis/starvation ketoacidosis
P‐ paraldehyde
I‐ isoniazid, iron, ibuprofen
L‐ lactate (ie. Seizures, shock)
E‐ ethylene glycol, EtOH
S‐ salicylates
Normal Anion Gap
• When a metabolic acidosis is caused by the primary LOSS of bicarb, this is coutnerbalanced by a gain in chloride ions to maintain charge neutrality
• A proportional increase in Cl‐ leaves the AG unchanged
• Common causes of a normal AG metabolic acidosis:
•
•
•
•
Diarrhea (loss of HCO3‐ in the stool)
Early renal insufficiency (increased bicarb loss in the urine)
Infusion of isotonic saline (Cl‐ conc. In saline > conc. In ECF)
Renal tubular acidosis
Management of High AG Metabolic Acidosis
• Many different etiologies involving varied forms of treatment
• Main point is to TREAT THE UNDERLYING CAUSE
• Will focus on lactic acidosis and diabetic ketoacidosis
Lactic Acidosis
• Lactate is the end product of anaerobic glycolysis
• Occurs when O2 utilization by cells is impaired
• Ie. In shock, sepsis, seizures
Thiamine deficiency (thiamine acts as a co‐factor to initiate pyruvate oxidation in the mitochondria)
• Primary goal in management is to correct the underlying metabolic abnormality
• Ie. treat the sepsis if patient is septic!
• Some studies have shown that therapy aimed at correcting the pH is of questionable value
Lactic Acidosis: “Controversies in Management”
1. Is Acidosis Actually Harmful?
• No major harmful effects have been shown from acidosis alone
• It is the underlying metabolic abnormality that is harmful
• Some clinical studies have shown an impairment in myocardial contractility
• However, acidosis also stimulates catecholamine release from the adrenals and produces vasodilation
• So impaired contractility is less of a concern
• Acidosis may also play a protective role in the setting of shock
• In vitro studies have shown extracellular acidosis to protect energy‐
depleted cells from apoptosis
Lactic Acidosis: “Controversies in Management”
2. Bicarbonate is Not Likely an Effective Buffer
• Sodium bicarbonate is the standard buffer used in lactic acidosis
• However, has limited success in raising the serum pH
• It is the underlying metabolic abnormality that is harmful
• Why?
• Dissociation constant (pK) for carbonic acid is 6.1
• This means that at pH=6.1, 50% of the acid is dissociated
Lactic Acidosis: “Controversies in Management”
2. Bicarbonate is Not Likely an Effective Buffer
• Buffers are most effective within 1 pH on either side of the pK
• SO, effective range should be a serum pH between 5.1‐7.1
• Therefore, bicarbonate is not expected to be an effective buffer in the usual serum pH range
Lactic Acidosis: “Controversies in Management”
3. Adverse Effects of Bicarbonate
• Infusion of large amounts of bicarbonate can shift the equation to the left and produce a CO2 load that must be removed by the lungs
Lactic Acidosis
How to manage:
• Sodium bicarbonate does not seem to have a role in the management of lactic acidosis
• Management aimed at treating underlying cause for abnormality
• However, in the setting of severe acidosis (pH<7.1), may want to try an infusion of bicarbonate by administering ½ the estimated bicarbonate deficit Ketosis
• In conditions of reduced nutrient intake, adipose tissue releases free fatty acids
• Metabolized in the liver to form ketones
• can be sued as oxidative fuel by the body
• Normal serum ketone concentrations are negligible, but can increase 10x after only 3 days of starvation
• Ketones are strong acid, and ketosis produces a progressive metabolic acidosis
Diabetic Ketoacidosis
• Often results from inappropriate insulin dosing, but can be triggered by concurrent illness (such as infection)
• Up to 20% of pts are not prior known‐diabetics
• Clinically, look for a combination of:
• Hyperglycemia
• Serum bicarbonate <20 mEq/L
• Elevated anion gap
Diabetic Ketoacidosis ‐
Management
• Insulin
• IV bolus of 0.1 units/kg, followed by continuous infusion at 0.1 U/kg/hr
• Check BG levels every 102 hours • Fluids
• If pt is stable, use crystalloids; otherwise use colloids
• Start with NS at a rate of 1L/hr for the first 2 hours, then decrease to ½ NS at 250‐500cc/hr
• Can add dextrose once glucose levels normalize
• Potassium
• Insulin therapy causes a intracellular shift of K+
• Can dramatically decrease K+ levels
• Start K+ replacement therapy as soon as possible
• Serial electrolyte checks
• Bicarbonate
• Not shown to improve outcome in DKA
Case 1:
• 47M with crush injury from construction site
‐ABG ‐ 7.2 / 32 / 96 / 15
‐Na‐ 135 / K‐5 / Cl‐ 98 / HCO3‐ 15 / BUN‐ 38 / Cr‐ 1.7
‐CK‐ 646
Use pH – low, therefore acidemic
Look at pCO2, HCO3 – low bicarb, therefore metabolic acidosis
Anion Gap = 135 ‐ (98 + 15) = 22
anion gap metabolic acidosis
Winters Formula pCO2 = 1.5 (15) + 8 ± 2 = 32.5
compensated (actual pCO2 is comparable to calculated one)……no separate respiratory disorder
Delta Gap = 22 ‐ 10 = 12
Corrected HCO3 = 12 + measure HCO3 = 12 + 15 = 27
Slightly above normal range of bicarb……mild metabolic alkalosis
Assessment: Compensated elevated anion gap acidosis with mild metabolic alkalosis secondary to crush muscle injury and possible vomiting. Case 2:
• 55F with SBO presents with nausea and vomiting.
• ABG ‐ 7.49 / 40 / 98 / 30
• Na‐ 140 / K‐ 2.9 / Cl‐ 92 / HCO3‐ 32
Use pH – high, therefore alkalemic
Look at pCO2, HCO3 – high bicarb, therefore metabolic alkalosis
Winters Formula pCO2 = 1.5 (30) + 8 ± 2 = 55
UNcompensated (measured pCO2 is lower than calculated one)……therefore a primary respiratory alkalosis is also present
Assessment: Mixed metabolic alkalosis and respiratory alkalosis secondary to vomiting and likely increase respiratory rate
Case 3:
70M with history of CHF presents with increased
shortness of breath and leg swelling.
-- ABG - 7.24 / 60 / 52 / 27
Use pH – Low, therefore acidemic
Look at pCO2, HCO3 – both abnormally high, therefore likely a mixed disorder. PCO2 is high and represents respiratory acidosis (consistent with PH). This is likely the primary mechanism given the presentation.
Is respiratory process acute or chronic?...... Change in pCO2 = 60‐ 40 =20.
‐ If acute, expected compensation is ↑[HCO3] = 1 mEq/L for every 10 mm Hg ∆pCO2……therefore elevation in [HCO3‐] = 20/10 × 1 = 2
‐ This should increase the [HCO3] to around 26
Assessment: Acute respiratory acidosis likely secondary to pulmonary edema.