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



pH, HCO3
12-24 hours for complete activation of
respiratory compensation
PCO2 by 1.2mmHg for every 1 mEq/L HCO3
The degree of compensation is assessed via
the Winter’s Formula
PCO2 = 1.5(HCO3) +8  2

Metabolic Gap
Acidosis
◦M - Methanol
◦U - Uremia
◦D - DKA
◦P - Paraldehyde
◦I - Infection
◦L - Lactic Acidosis
◦E - Ehylene Glycol
◦S - Salicylate

Non Gap Metabolic
Acidosis
◦Hyperalimentation
◦Acetazolamide
◦RTA (Calculate urine
anion gap)
◦Diarrhea
◦Pancreatic Fistula
The Anion Gap:
 In the body
cations = anions
 Not all of the anions are measured in routine
laboratory analysis

(
)
[K + Na+] – [Cl-] + [HCO3-] = 12
There are more measurable cations compared to
measurable anions in the serum; therefore, the
anion gap is usually positive. Because we know that
plasma is electro-neutral we can conclude that the
anion gap calculation represents the concentration
of unmeasured anions.
The anion gap varies in response to changes in the
concentrations of the above-mentioned serum
components that contribute to the acid-base
balance. Calculating the anion gap is clinically
useful, as it helps in the differential diagnosis of a
number of disease states.

Anion gap can be classified as either high, normal or low.
Laboratory errors need to be ruled out whenever anion gap
calculations lead to results that do not fit the clinical picture.
Methods used to determine the concentrations of some of the
ions used to calculate the anion gap may be susceptible to
very specific errors. For example, if the blood sample is not
processed immediately after it is collected, continued
leukocyte cellular metabolism may result in an increase in the
HCO3− concentration, and result in a corresponding mild
reduction in the anion gap. In many situations, alterations in
renal function (even if mild, e.g., as that caused by
dehydration in a patient with diarrhea) may modify the anion
gap that may be expected to arise in a particular pathological
condition.
The Anion Gap:
 In the body
cations > anions
 Not all of the anions are measured in routine
laboratory analysis

(
)
[Na+] – [Cl-] + [HCO3-] = 8-16
The Anion Gap:
 The usual unmeasured anions that account
for the “gap” are:
◦ Albumin
◦ Phosphates
◦ Sulphates
A high anion gap indicates that there is loss of
HCO3− without a concurrent increase in Cl−.
Electroneutrality is maintained by the elevated
levels of anions like lactate, betahydroxybutyrate and acetoacetate, PO4−, and
SO4−. These anions are not part of the anion-gap
calculation and therefore a high anion gap
results. Thus, the presence of a high anion gap
should result in a search for conditions that lead
to an excess of these substances.

A high anion gap indicates acidosis. e.g. In
uncontrolled diabetes, there is an increase in
ketoacids (i.e. an increase in unmeasured anions)
and a resulting increase in the anion gap.


Ketoacidosis is a metabolic state associated with
high concentrations of ketone bodies, formed by
the breakdown of fatty acids and the deamination
of amino acids. The two common ketones
produced in humans are acetoacetic acid and βhydroxybutyrate.
Ketoacidosis is a pathological metabolic state
marked by extreme and uncontrolled ketosis. In
ketoacidosis, the body fails to adequately regulate
ketone production causing such a severe
accumulation of keto acids that the pH of the blood
is substantially decreased. In extreme cases
ketoacidosis can be fatal



Ketoacidosis is most common in untreated type 1
diabetes mellitus, when the liver breaks down fat
and proteins in response to a perceived need for
respiratory substrate. Prolonged alcoholism may
lead to alcoholic ketoacidosis.
Ketoacidosis can be smelled on a person's breath.
This is due to acetone, a direct byproduct of the
spontaneous decomposition of acetoacetic acid
It is often described as smelling like fruit or nail
polish remover.
High Anion Gap Acidosis:
Type
Anion:
 Lactic
lactate
 Diabetic
ketones
 Uremia
sulphate/phosphate
 ASA
salicylate
 Methanol
formate
 E. Glycol
oxalate


Uremia is a term used to loosely describe the illness
accompanying kidney failure, in particular the
nitrogenous waste products associated with the failure
of this organ.
In kidney failure, urea and other waste products, which
are normally excreted into the urine, are retained in the
blood. Early symptoms include anorexia and lethargy,
and late symptoms can include decreased mental acuity
and coma. Other symptoms include fatigue, nausea,
vomiting, cold, bone pain, itch, shortness of breath, and
seizures. It is usually diagnosed in kidney dialysis
patients when the glomerular filtration rate, a measure
of kidney function, is below 50% of normal

Increases from: antifreeze, solvent, fuel, and
as a denaturant for ethanol. Methanol is also
produced naturally in the anaerobic
metabolism of many varieties of bacteria
Why do we need oxygen?
 For oxidative phosphorylation
What is oxidative phosphorylation?
 ADP + Pi = ATP (requires energy)
 The formation of ATP
What does the oxygen do?
Lactic Acidosis
Glycolysis:
GlucosePyruvateAcetyl CoA
Kreb’s:
Acetyl CoANADH & FADH
Electron transport chain (ETC)
NADH & FADHATP


The bulk of ATP is generated in the electron
transport chain (ETC) in the mitochondrion
The energy for creating the high-energy
phosphate bond is generated at several points
in the ETC. So are hydrogen ions
High -
Oxygen allows for ATP formation in
an electrically-neutral biologically safe manner
Lactic Acidosis
 Type A: failure of oxidative
phosphorylation (PyruvateLactate)
 Type B: lactate production
overwhelms lactate
metabolism
Failure of ETC:
Decreased Oxygen delivery
◦
◦
◦
◦
Shock of any type
Severe hypoxemia/hypoxia
Severe Anemia
Inhibitors (CO, CN); left shifts
Lactate production overwhelms lactate
metabolism (not anaerobic)
 Malignancies (after chemotherapy)
 Hepatic failure
 Drugs (biguanides, AZT, INH)


Treat the underlying cause
Lower the H+ concentration
Ex:
Profound rapid blood loss
Normal Saline boluses 1-2 Liters, maintain
systolic BP of 90 or more
Transfusion of blood and products
Circulatory support
Lower the H+ concentration
H+ + HCO3-  H2CO3  H2O + CO2
Lower the paCO2 by increasing minute
ventilation
Lower the paCO2 by
increasing
minute ventilation
For every 1meq/l drop in HCO3- from 25, paCO2
should decrease by ~ 1 torr
“Normal” paCO2 in the face of HCO3- 10 is 25 (40
subtracted by 15)
Intravenous bicarbonate administration:
Pro:
lowers H+ concentration (pH)
improves pressor response
improves myocardial function
Con: worsens intracellular acidosis
may worsen outcome
hypertonic
Bottom line:
If there is adequate circulation
and if minute ventilation is appropriate,
some bicarbonate administration is
warranted.
Don’t aim for full correction, continue
arterial blood analysis
With hemodynamic instability:
Severe acute bleed
Sepsis
Trauma
Increase minute ventilation
Analyze arterial blood
Judicious intravenous NaHCO3-