Metabolic acidosis

download report

Transcript Metabolic acidosis

Metabolic acidosis
• Metabolic acidosis – a primary decrease in
serum HCO3
• HCO3 also low in respiratory alkalosis
• Metabolic acidosis without a low serum pH
can occur if there is another acid-base
disturbance that increases the serum
HCO3 e.g. metabolic alkalosis from
vomiting
Renal control of serum pH
• Serum pH is maintained in a tight range
via lung control of pCO2 and renal control
of HCO3
• The kidneys control HCO3 by
1) reabsorbing all filtered HCO3 (about
4000 mEq/day); defect in: proximal RTA
2) excreting acid produced from diet
(about 70 meq/day) primarily as NH4+ and
HPO4; defect in: distal RTA
Respiratory compensation in
metabolic acidosis
• The change in pCO2 is 1.2 times the
change in HCO3 or alternatively put a
thumb over the 7 in the pH
• If is adequate respiratory compensation is
simple metabolic acidosis
• If inadequate respiratory compensation is
a mixed disorder – combined metabolic
and respiratory acidosis
Anion Gap
• Na+ - (Cl- + HCO3) = 12 +/- 4 meq/L
• Outside of USA most countries exclude the K+
• Another way of thinking of this formula is as
unmeasured anions – unmeasured cations
• Unmeasured anions - mostly albumin,
phosphorous, and sulfate
• For each 1 gm decrease in serum albumin the
expected anion gap would go down by 2.3
• Unmeasured cations - Mg, Ca, paraproteins
Anion gap (AG) interpretation
• Normal initially described as 12 +/-4 but
with new ion selective electrodes normal in
some hospitals significantly lower
• An insensitive screen for mild to moderate
deviations from normal
• Pronounced elevations (e.g. >30) - the
identity of the anion is usually obvious
• Less pronounced elevations – the
unmeasured anions identity often not clear
delta HC03/delta AG ratio
• Typically is a 1:1 ratio between increase in anion gap
and a decrease in HCO3
• If the change in HCO3 exceeds the change in anion gap
by 3 mEq/L this suggests that both a high and normal
anion gap acidosis are present
• If the change in anion gap is more than the change in
HCO3 probably both a metabolic acidosis and metabolic
alkalosis are present
• Conversion of high anion gap to normal anion gap can
occur if patient excretes the anion from the acid but
retains the H+
High AG metabolic acidosis
•
•
•
•
•
•
•
Glycols - ethylene and propylene
Oxoproline – pyroglutamic acid
L - lactic acid
D - lactic acid
Methanol – formic acid
Aspirin – multiple organic acids
Renal failure – multiple organic and inorganic
acids
• Ketoacidosis – B-OH butyric and acetoacidic
acids
Hyperlactatemia
• Elevated serum lactate without acidosis
• Normal lactate level in critical care patient
<2 mm/L
• Minor elevations (as low as 0.75 mm/L)
correlate with mortality in patients in ER,
ICU, or with sepsis
• Lactate-based therapies in Rx of sepsis
Lactic Acid
• Lactic acid can exist in two forms: L-lactate
and D-lactate. In mammals, only L-lactate
is a product of metabolism.
• The lab measures only L-lactate
• Normal daily production of lactate 15 to 30
mmol/kg per day
• All of this lactic acid is converted to CO2
and water with no net acid-base effect
Type A lactic acidosis
• Mechanism – overproduction of lactic acid
due to shock, hypoxemia, profound
anemia, carbon monoxide, seizures
(transient)
• Anaerobic glycolysis of 1 mole of glucose
generates ATP but only about 10% of that
generated with aerobic glycolysis
• With marked anoxia body can generate 12
mm/min of lactic acid or 12 meq/min of H+
Anaerobic lactate metabolism
• Glucose enters glycolytic cycle in
cytoplasm to form pyruvate.
• Since no 02 for oxidative phosphorylation
pyruvate can not enter the mitochondria to
generate ATP but is converted to lactate
• Lactate generated in muscle goes to liver
which converts it to glucose which can be
cycled back to muscle (Cori cycle)
Type B lactic acidosis
• Mechanism – not due to overproduction of lactic acid but
usually due to decreased liver utilization from genetic
defects, drugs, vitamin deficiencies, toxins
• In comparison to type A - much less common, in some
cases due to a genetic defect only manifested by a drug
or toxin, the acidosis not as severe, since acidosis not as
severe may be easier to treat with HCO3
• Causes - congenital defects in glucose and lactate
metabolism especially in genetic mitochondrial diseases,
liver disease, diabetes, neoplasms, vitamin deficiencies,
toxins, drugs
Drugs associated with lactic
acidosis
•
•
•
•
•
•
•
•
•
highly active retroviral agents
ethylene glycol, methanol, propylene glycol
salicylate
metformin, phenformin
clenbuterol - beta-blocker contaminant in heroin
linezolid
propofol – propofol infusion syndrome
propylene glycol solvent - lorazepam
nitroprusside – cyanide formation
Metformin and lactic acidosis
• Package insert – do not give if creatinine
>1.4 in female or >1.5 in male
• Precipitated by worsening of CKD via
NSAIDs, ACE inhibitors, or contrast
• OD or therapeutic dosage
• Reports of 30-50% mortality
• CRRT can remove the metformin and also
help correct the lactic acidosis
Metformin-induced lactic acidosis
(MALA) recent article titles
• Does metformin increase risk of fatal or
nonfatal lactic acidosis?
• Metformin associated lactic acidosis - is it
really just an association?
• Metformin - potential benefits and use in
chronic kidney disease
• Metformin does not increase risk for lactic
acidosis in type 2 diabetes mellitus
D-Lactic acidosis
• Certain bacteria in the GI tract may convert carbohydrate (cellulose)
into organic acids – primarily D-lactic acid which when absorbed is
very slowly metabolized
• Most patients who develop D-lactic acidosis have slow GI transit as
with blind loops, obstruction, drugs decreasing GI motility
• Often exacerbated by increased carbohydrate intake or antibiotics
allowing for overgrowth of lactobacilli
• CNS findings – usually is associated with confusion, dysarthria,
ataxia (due to other toxins made by the bacteria)
• D-lactate is not measured when order lactic acid level
• Treatment - restrict carbohydrates, hydrate, give bicarbonate
MELAS
• Mitochondrial encephalopathy, lactic
acidosis, stroke-like episodes
• Usually presents with seizures
• Almost always diagnosed in childhood
• Diagnosis usually made by molecular
genetic testing of mitochondrial DNA
• Adults – case reports, suspect if seizures
worsened by valproic acid
Alcoholic ketosis
• Usually a history of long-term alcohol use,
reduced food intake, nausea and vomiting
• Starvation ketosis – similar but less severe
• Ketone measurement may be normal since beta
hydroxybutyric acid may be 90% of acid present
• Increased incidence of sudden death
• Treatment – glucose (increases insulin), normal
saline to correct volume loss, thiamine to
prevent Wernicke’s encephalopathy, do not
need to give HCO3 since as the abnormality
corrects the ketoacids are converted to HCO3
Pyroglutamic acidosis
• Consider if unexplained AG acidosis and
acetaminophen ingestion - either OD or
therapeutic dose
• Some studies have found a high incidence of
this if unexplained AG acidosis and CNS
changes
• Glutathione levels reduced due to the oxidative
stress of an acute illness and suppression from
acetaminophen
• Reduced glutathione levels lead to increased
pyroglutamic acid levels (oxoproline)
Osmolar Gap
• Serum Osm = 2 (Na) + BUN/2.8 + glc/18
• Calculated and determined Osm should
agree within 10 to 15 mOsm/kg.
• If not, then serum Na may be spuriously
low OR osmolytes other then Na, glc or
urea have accumulated.
• The osmolar gap is a reliable and helpful
tool when screening for toxin-associated
high AG acidosis
• Must correct for ETOH if present.
Etylene glycol and methanol
metabolism
• The major toxicities of these agents are not from
the agents themselves but from metabolites
• Methanol produces formic acid & formaldehyde
and ethylene glycol produces glycolic acid
• Both are metabolized by alcohol dehydrogenase
so if the patient has consumed ETOH this would
slow formation of the lethal metabolites
• Alcohol dehydrogenase much more avidly binds
to ETOH than to methanol or ethylene glycol
• Fomepizole – alcohol dehydrogenase specific
inhibitor, much more effective than ETOH
Ethylene glycol poisoning
• Suicide attempt, substitute for alcohol, homicidal
• antifreeze
• 3-phase clinical picture
1) 4-12 hrs - CNS/GI phase: inebriation, mimics EtOH
intoxication
2) 12-24 hrs - worse acidosis, cardiopulmonary
dysfunction, increased HR, increased BP, myocarditis,
pneumonia, pulmonary edema, myositis
3) 36-72 hrs - oliguric renal failure
• Clues for this diagnosis - crystals in the urine (due to
calcium oxalate formation from the ethylene glycol)
• MW of ethylene glycol=46 so a level of 20 mg/dl would
increase AG by 4 and a level of 100 by 16
Methanol poisoning
• Methyl alcohol or wood alcohol
• Can be from bootleg alcohol unknowingly
contaminated
• As a thinner for shellac and varnish, windscreen
and gasoline antifreeze, fuel for alcohol burning
devices
• No symptoms for the first 12 hours
• 1 ounce can produce a blood level of 100 mg/dL
• Toxicity primarily CNS and optic nerve damage
• Molecular weight is 32 so a level of 20 mg/dl
produces an AG of 6 and 100 an AG of 31
Crtieria for Rx in methanol or
ethylene glycol poisoning
• plasma concentration >20 mg/dl OR
• documented recent history of ingestion of
toxic amounts and osmolal gap >10 OR
• at least 3 of the following – arterial
pH<7.3, serum HCO3<20, osmolal gap
>10, oxalate crystalluria (with ethylene
glycol)
• Unexplained anion gap: NEJM 2009:2216
Hemodialysis for methanol or
ethylene glycol
• Goal – to prevent end organ toxicity
• Mechansim – corrects metabolic
abnormalities and eliminates
nonmetabolized methanol or EG
• Indications – level>50 mg/dL, HCO3<15 or
pH<7.3, optic injury from methanol
Propylene Glycol Toxicity
• An alcohol used to enhance water solubility of
many hydrophobic IV medications
(lorazepam, diazepam, esmolol, nitroglycerin)
• Propylene glycol toxicity from solvent
accumulation has been reported in 19%-66%
of ICU patients receiving high dose
lorazepam or diazepam >2 days.
• Signs of toxicity—agitation, coma, seizures,
tachycardia, hypotension
Salicylate intoxication
• Respiratory alkalosis usually accompanies
ASA intoxication, but metabolic acidosis
may be prominent in children
• The toxicity is primarily due [ASA] in
tissues
• The uncharged form HASA crosses cell
membranes easily so a primary goal is to
prevent metabolic acidosis since would
increase conversion of ASA to HASA
ASA intoxication Rx
• Reduction of HASA movement into cells
(especially brain cells) – NaHCO3
• Excretion of ASA in urine by alkalination NaHCO3, acetazolamide (but competes
with protein binding of ASA and may
increase free levels, if not carefully
monitored can cause metabolic alkalosis)
• Hemodialysis – consider: ASA >60 mg/dl,
institute >90 mg/dL
Normal anion gap metabolic
acidosis
• Gastrointestinal HCO3 loss – diarrhea, loss of
pancreatic or biliary secretions, ureteroileostomy
or ureterosigmoidostomy, sevelamer
• Renal acidification defects – RTA, CKD,
hypoaldosteronism; drugs (Topamax,
acetazolamide, spironolactone, amiloride ,
trimethoprim, cyclosporine, pentamidine, toluene
from glue sniffing)
• Administration of acid – cationic aminoacids in
TPN
Estimation of urine NH4+
• The acid excreted by the kidney each day
is excreted primarily in the form of NH4+
• Acidotic patient with normal AG a
decrease in the urine NH4+ suggests a
defect in renal acid excretion – distal RTA
• Estimation of urine NH4+ can be done by
measuring urine AG (urine Na + K – Cl)
• Negative value suggests high urine NH4+
Adverse consequences of severe
acidemia
• Cardiovascular – impaired contractility,
vasodilatation, venoconstriction,
sensitization to arrhythmias, reduced
response to pressors.
• Respiratory - hyperventilation, respiratory
muscle fatigue, dyspnea
• Metabolic -- insulin resistance, inhibition of
anaerobic glycolysis, protein degradation,
decreased ATP synthesis, hyperkalemia
Complications of bicarbonate
therapy
• Overshoot alkalosis – due to conversion of
lactate or acetate to HC03
• Increase in lactate generation in lactic
acidosis
• Volume expansion
• Increased CO2 production
• Hypocalcemia
• Hypernatremia – IV NaHCO3 (8.5%)
• Cardiac depression
NaHCO3 dose estimation
• Volume of distribution of HCO3 is ½ of the
body weight, may be higher with severe
acidosis
• To correct the serum HCO3 from 5 to 10
meq/L in a 100 kg man would be 5 x 50 or
250 meq which is about 5 amps of
NaHCO3
• 1 amp IV NaHCO3 = 48 meq in 50 cc
• 1 gram po NaHCO3 = 12 meq