Answer is A (Methaemoglobinemia) Pronounced cyanosis together with chocolate brown colour of 'freshly drawn blood suggests a diagnosis of methaemoglobinemia Methaemoglobinemia * * * Methaemoglobinemia is an uncommon but distinct cause of central cyanosis in the absence of hypoxemia or cardio vascular compromise Methaemoglobinemia occurs when a significant concentration of hemoglobin (Hb) is oxidized to methaemoglobin (Met Hb) When the haem moety (iron atoms) of' Hb molecule encounter a strong oxidizing agent iron loses an electron and switches from the Ferrous (2+) to Ferric (3+) state turning Hb to 'Met Hb' Methaemoglobin has such high oxygen affinity that viually no oxygen is delivered Presentation * * Methaemoglobinemia most commonly presents as cyanosis unresponsive to supplemental oxygen The most notable physical examination finding is generalized cyanosis which can manifest as muddy brown dark mucus membranes before proceding to global skin discolaration 'The charachteristic muddy appearance (chocolate brown) of freshly drawn blood can be a critical clue'-*Blood appears dark brown, brownish, muddy or chocolate in colour immediately after withdrawal. In contrast to normal venous blood, the color does not change with addition of oxygen or agitation in the air'- Diffirential diagnosis in Internal Medicine Methaemoglobinemia > 15% cause symptoms of cerebral ischaemia Methaemoglobinemia > 60% is usually lethal Diagnosis * The hest Methaemoglobinomia is * Methaemoglohin Assay' Treatment * The most effective emergency management for methaemaglobinemia is administration of Methylene bluee which serves as an antidote (intravenous) Methylene blue is not effective in patients with methaemoglobinemia due to Hemoglobinopathy MQ (Haemoglobin M) Methylene blue is contraindicated in patients with G6 PD deficiencyQ since it can cause severe hemolysis due to its potential for oxidation Outline of The Four Main Pathways to MetHb Production 1. Congenitally abnormal hemoglobin: Hemoglobin M Hemoglobin M is passed as an autosomal dominant trait affecting either the alpha or beta chain of hemoglobin; homozygous Hb M affecting both alpha and beta chains is incompatible with life. Amino acid substitution (often a tyrosine for histidine) near the heme iron facilitates iron oxidation. 2. Inherited enzyme deficiencies: NADH-dependent cytochrome b5 -reductase and cytochrome bc deficiency. Deficiency of either cytochrome b5 or its reducing enzyme, cytochrome b5-reductase, decreases reduction of MetHb back to Hb 3. Nitrite (NO2), other oxidants and oxygen-reducing compounds Nitrites are a common oxidizing source of MetHb production. Reducing agents paradoxically produce methemoglobinemia by reducing oxygen to a free radical or water to 1-1,O2, which then oxidizes hemoglobin. 4. "Sensitive" hemoglobin: Blue baby syndrome Bacteria in the immature gastrointestinal tracts of infants conve nitrate (NO3) to the powerful oxidant nitrite (NO,). Infants have a relative NADH-dependent reductase deficiency (only 50% of adult levels) and are more susceptible to oxidative injury.