Metabolic Pathways of Toxic Alcohols
Panel A shows the metabolic pathways of toxic alcohols. Alcohol dehydrogenase and aldehyde dehydrogenase sequentially oxidize the toxic alcohols. Alcohol dehydrogenase catalyzes the first oxidation of the toxic alcohols and is an important target for antidotal therapy. The enclosed boxes highlight the putative toxic metabolites. Methanol is metabolized to formic acid, ethylene glycol to oxalic and glycolic acid, diethylene glycol to 2.hydroxyethoxyacetic acid and glycolic acid, and propylene glycol to D-lactic and L-lactic acid. Panel B shows the time course of changes in the osmolal and anion gaps with and without coingested ethanol. An increased osmolal gap is prominent early owing to
the accumulation of the un.ionized alcohols. As metabolism proceeds, the osmolal gap declines with the formation of ionized metabolites. Conversely, the serum anion gap is lowest before the alcohol is metabolized and increases with the formation of ionized metabolites. The time course of these changes in both parameters varies among the
alcohols. They typically evolve over several hours to over a day. Coingested ethanol impedes metabolism (dashed lines) and delays the onset of the high anion-gap acidosis.
#Pathophysiology #Toxicology #ToxicAlcohols #Metabolism #Pathways #Osmolar #OsmolalGap #AnionGap #Timeline #NEJM
Toxic Alcohol Ingestion: Clinical Features, Diagnosis, and Management
Methanol intoxication:
• Accidental or intentional ingestion of adulterated alcohol or products with methanol; rare cases of inhalation of methanol
• Dx: Osmolal gap with HAGAc, Visual difficulties with optic papillitis
Ethylene glycol intoxication:
• Accidental or intentional ingestion of antifreeze, alcohol adulterated with ethylene glycol, or products with ethylene glycol
• Dx: Osmolal gap with HAGAc, ARF with osmolal gap, Calcium oxalate crystals in urine, monohydrate or dihydrate
Diethylene glycol intoxication:
• Ingestion of contaminated medication or products with diethylene glycol
• Dx: Osmolal gap with HAGAc, Osmolal gap with ARF, Osmolal gap with coma
Propylene glycol intoxication:
• Intravenous administration of medication with propylene glycol; rare ingestion of products with propylene glycol
• Dx: Osmolal gap with or without LA
Isopropanol intoxication:
• Accidental or intentional ingestion of rubbing alcohol
• Dx: Osmolal gap without HAGA
Alcoholic ketoacidosis:
• Binge drinking often in alcoholic patients associated with starvation and often vomiting
• Dx: HAGA, trace positive or negative nitroprusside reaction with increase with H2O2; hypoglycemia; osmolal gap
#Alcohol #Ingestion #diagnosis #toxicology #comparison #table #management #treatment
Toxic Alcohol Ingestion: Methanol
Solvent found in cleaning and printing solutions, adhesives, stains, paint removers,
antifreeze agent in windshield wiping fluid, camp stove fuel, gasoline additive
Pharmacology:
- Peak serum concentration 30-60 minutes, elimination half-life 12-20 hours
- Permanent blindness reported at as little as 0.1 mL/kg (6-10 mL in adults)
- Lethal dose = 1-2 mL/kg
- Metabolite (eg. formic acid) causes toxicity, but does NOT cause osmolal gap
#Diagnosis #Management #Toxicology #Methanol #Ingestion #ALiEM
Elevated Globulin - Protein Gap (Total Protein - Albumin > 4)
Work-up of an Elevated Globulin Gap:
• An elevated globulin gap (>4 g/dL) should always be evaluated.
• (Total protein concentration minus albumin concentration = "gamma gap")
• The first step in evaluation is to determine whether it represents a monoclonal or polyclonal gammopathy.
Causes of Monoclonal Gammopathy Include:
• MGUS
• Multiple myeloma
• Waldenstrom’s macroglobulinemia
• Amyloidosis
• Lymphoma
• Smoldering multiple myeloma
• Plasma cell leukemia
• Solitary plasmacytoma
• Heavy chain disease
• Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS syndrome)
• Solitary plasmacytoma
• Castleman disease
• AL (light chain) amyloidosis
Causes of Polyclonal Gammopathy Include:
• Viral infections (acute HIV, HBV, EBV, VZV, hepatitis C)
• Connective tissue disorders (RA, Temporal arteritis, Sarcoidosis)
• Liver disease: Cirrhosis, ETOH, autoimmune hepatitis, PBC, PSC, Viral hepatitis
• Malignancies: Solid tumors, ovarian tumors, lung cancers, HCC, renal tumors, gastric tumors
• Hematology: Lymphoma, Leukemia, Thalassemia, Sickle cell anemia
• Other causes of persistent inflammation (acute phase reactants will cause an increase in the globulin gap)
Next Step: Etiology of Protein Gap:
• SPEP, immunofixation and free light chain assay
• An abnormal free light chain ratio indicates overproduction of either kappa or lambda light chain
• Normal kappa/Lambda FLC ratio is 0.26 - 1.65
SPEP can:
1. Detect a spike
2. Determine its size (amount)
SPEP cannot:
1. Confirm monoclonality
2. Comment on type (heavy/light chain)
3. Always detect a small spike
Immunofixation:
1. Confirm monoclonality
2. Determine heavy/light chain specificity
3. Detect smaller M spikes
#Globulin #Protein #Gap #ProteinGap #differential #diagnosis #hematology
Salicylate Toxicity - Diagnosis and Management
Consider if:
1) Patient is hot and altered
2) You see tachypnea with no respiratory cause
3) Labs show anion-gap metabolic acidosis
4) Presentation seems like DKA, sepsis, PNA, meningitis
5) History of acute or chronic ingestion/exposure
Symptoms: Nausea, Vomiting, Tinnitus, Hearing loss, Dizziness, Altered, Seizure, Coma
Exam: Tachypnea, Tachycardia, Elevated temp, Diaphoresis, Pulmonary edema, Shock
Labs: Anion-Gap Metabolic Acidosis, Respiratory Alkalosis, High Lactate, Low Potassium, Low Glucose, Salicylate level
- Toxic Salicylate Level: 150mg/kg
Management:
1) Resuscitation
2) Urine pH > 7.5 with Alkalinzation
3) Glucose > 4.5 mmol/L
4) K > 4.5 mmol/L
5) Dialysis
By Sarah Foohey @SarahFoohey
#Salicylate #Aspirin #Toxicity #Toxicology #diagnosis #management #Treatment
Causes of Thrombocytopenia and Platelet Disorders - Differential Diagnosis and Workup
History:
- Prior platelet count, family history
- Medications
- Chronicity/severity
- History of bleeding (petechiae, ecchymoses, epistaxis, gingival bleeding, hematemesis, melena, heavy menstrual
- Recent procedures
- Infection exposure (l MD SOAP)
- Risks factor for HIV, HCV
- Alcohol use
- Dietary practices that could cause nutrient deficienies
Labs:
- Basic labs for decreased PLT count: CBC(.plateletcount), peripheral blood smear, HIV/HCV testing
- Lab for decreased PLT in selected cases: INR/PT, aPTT(liver disease, decrease vit K), H. pylori test (GI symptoms/endemic country), thyroid function test, ANA (e.g., SLE), anti-phospholipid antibodies, Quantitative IgA, IgG, IgM (CVID, WAS), (neurologic/psychiatric changes), high MCV anemia (vegan, gastric bypass), LFT (liver disease), HBsAg/anti-HBc (rituximab tx candidate)
- Bone marrow evaluation: not required in all patients with thrombocytopenia. However, it may be helpful in some patients if the cause of thrombocytopenia is unclear, or if a primary hematologic disorder is suspected. When do you do a BM aspiration/biopsy? Refractory ITP, unexplained pancytopenia, dysplasia on the smear
Dr. Jorge Cortés @Jcortesizaguirr
#Thrombocytopenia #Platelet #Disorders #Differential #Diagnosis #Causes #Workup #hematology
