Case Study: Methanol Poisoning of a Child

Case Study Methanol Poisoning of a boor cosmosIn this PBL, we observe a case of methanol poisoning in a child. We volition first define the unfamiliar term of tertiary superintend centre and proceed to understand erosive base homeostasis in the personify, the basis for methanol poisoning. thusly we will look at how ethanol and methanol ar metabolised in the body followed by how methanol poisoning actually endures. We will also discuss how the osmolal chap is obtained using osmolality and osmolarity and lastly child abuse.Learning Objectives interpretation of unfamiliar terminologyAn overview of acid base homeostasis in the bodyHow ethanol and methanol are metabolised in the bodyHow does methanol poisoning workOsmolality and osmolarityChild abuse1. Unfamiliar term Tertiary dread centreA tertiary care centre is where a patient goes to when primary and secondary care have not been able to adequately treat the patient. Tertiary care centres are equipped with noblely trained st aff and highly dedicated health check equipment to cater to complex words or procedures as required by the patient. An example of a tertiary care centre would be the colorectal unit at The Royal London (1). Amareen was transferred to a tertiary care centre to receive more suitable care mainly due to the fact that she was so raw and suffering from methanol poisoning.2. Overview of acid base homeostasis in the bodyAcid base homeostasis is the regulation of hydrogen ions. The high the submerging of hydrogen ions, the lower the pH and vice versa. Acidic solutions have a high pH whereas alkaline solutions have a lower pH. The normal pH in the body is in the range of 7.35-7.45. A pH lower than 7.35 results in acidosis whereas a pH higher than 7.45 results in alkalosis.Acid base oddment has its basis in the Henderson-Hasselbalch equivalence shown in Figure 2. If we rearrange the equation, we see that bicarbonate and carbon dioxide directly affects the acid base balance.Figure 2 Hend erson-Hasselbalch Equation (3) in that location are trey main ways in which the body controls the acid base balance. These three systems usually work in concert. Firstly, there are physiologic buffers, each of which consist of a weak acid and its base salt or a weak base and its base acid. Physiologic buffers react immediately within seconds to the change in pH in the body. These buffer systems occur in both intra and extracellular parts of the cells. The main buffering systems for physiologic buffers are extracellular bicarbonate-carbonic acid buffering system, intracellular protein buffers and inorganic phosphate buffers in the bone. An overview of the physiologic buffer system is shown below in Figure 1.Figure 1 Physiologic buffer systems (2)If physiologic buffers are not nice to return the pH back to its normal value, pulmonary compensation contribute take place in the lungs. This works by eliminating or retaining carbon dioxide. change magnitude ventilation effort (hyperv entilation) and decreased ventilation effort (hypoventilation) are the two ways pulmonary compensation works. The changes in pulmonary compensation is rapid within a few minutes.The final compensatory mechanism, renal compensation in the kidney, starts when the previous two mechanisms have failed to regulate the pH take in the body. The kidneys prolong balance by excreting or conserving bicarbonate and hydrogen ions in the body. However, this compensatory mechanism is a long term regulator and takes longer, usually a few hours, to resolve to a change in acid base balance.The normal arterial blood gas values for partial pressure of carbon dioxide is 35-45 mmHg/ 4.7 kPa-6.0 kPa and bicarbonate dumbness is 22-26 mmol/L. A change in the partial pressure of carbon dioxide or bicarbonate concentration from normal levels results in respiratory or metabolic disorders respectively. This together with acidosis or alkalosis determined by the pH results in 4 main disorders arising. Figure 3 below shows the 4 different disorders and their respective compensatory mechanisms.Figure 3 Diagnosis of the four main acid base disorders and respective compensation mechanisms (4).In Amareens case, metabolic acidosis occurs. The major obtain is the high production of formic acid which is not excreted quickly from the body. This has caused a decrease in the bicarbonate concentration due to H+ combining with bicarbonate. By the law of mass reach using the Henderson- Hasselbalch equation, there is extra CO2 generated thus Amareen shows respiratory compensation via tachypneic breathing whereby the peripheral chemo receptors in the lungs are stimulated which stimulates the alveoli to try to exhale the bare(a) CO2. The exhalation of CO2 would in most cases be enough to correct the metabolic acidosis but in this case as methanol was ingested, external treatment was mandatory to save Amareens life.3. How methanol and ethanol are metabolised in the bodyEthanol metabolismEthanol, comm only known as drinking alcohol, is metabolised earlier by alcohol dehydrogenase in the liver. Once ingested, ethanol is quickly absorbed by the gastrointestinal tract and small intestines with concentrations reaching at uttermost level at 20-60 minutes (5). Ethanol is metabolised to acetaldehyde by alcohol dehydrogenase and then to acetate in the mitochondria via aldehyde dehydrogenase. Acetate is then metabolised to Acetyl CoA and subsequently to CO2 and water by the Krebs cycle in the mitochondria. Ethanol dismiss also be metabolised by two other pathways by cytochrome P450 2E1 (CYP2E1) in microsomes of the endoplasmic reticulum when there is a high ethanol consumption and by catalase in peroxisomes (6). The three ways ethanol is metabolised are illustrated in Figure 4 below.Figure 4 aerobic pathways of ethanol metabolism in the body (7)Methanol metabolismMethanol, commonly known as wood alcohol, rouse be absorbed by the body via inhalation, ingestion and skin exposure (8). In this specific case, Amareen ingests methanol. When methanol is ingested, it is quickly absorbed by the gastrointestinal tract with concentration reaching a maximum level at 30-90 minutes after ingestion (8). Methanol is primarily metabolised in the liver. In the first note, methanol is metabolised to formaldehyde by alcohol dehydrogenase. Then formaldehyde is subsequently metabolised to formic acid by formaldehyde dehydrogenase. Formic acid is finally metabolised into carbon dioxide and water in the presence of tetrahydrofolate. This final step proceeds very slowly and hence there is an accumulation of formic acid in the body which is the chief cause of methanol poisoning and will be discussed in the next section. Methanol metabolism is illustrated in Figure 5 below.Figure 5 Metabolism of methanol (9)4. How does methanol poisoning workSymptoms and CausesThe main characteristics of methanol poisoning are metabolic acidosis and ocular damage. Formic acid, the metabolite of methan ol and not methanol itself is considered to be toxic. The malignity of the toxicity correlates with the degree of metabolic acidosis rather than concentration of methanol. (10, 11) The accumulation of formic acid in the body has many detrimental effects if left untreated. The effects of methanol poisoning can be grouped into different phases (12). The phases are described in Table 1 below.Table 1 Different phases of methanol poisoningFormic acid has been shown to inhibit cytochrome C oxidase activity in mitochondria (14) which is similar to the action of cyanide, hydrogen sulphate and carbon monoxide (15). Cytochrome C oxidase is the last enzyme in the electron transport kitchen stove of the mitochondria which results in the synthesis of ATP (16). Thus, by inhibiting cytochrome C oxidase, there would be significant reduction in the synthesis of ATP resulting in cell hypoxia ahead(p) to cell injury and death (17, 18).The amount of formic acid in the blood is proportional to the in crease in the anion gap which measures the contribution of unmeasured anions to acidosis by using the formula Na+ + K+ Cl- HCO3- (19). A high anion gap of 20mmol/dL was observed in the arterial blood gas of Amareen when she was transferred to the tertiary care centre. A high anion gap indicates the loss of bicarbonate ions without concurrent loss in chloride ions. Thus, a low blood serum bicarbonate level is a reliable indicator of the severity of methanol poisoning. Other causes of a high anion gap are diabetes keto acidosis, lactic acidosis, ethylene glycol and salycilate.DiagnosisDiagnosis for Amareen was relatively easy as a history was available from her parents stating that she had ingested methanol. This allowed doctors to treat Amareen quickly and correctly to pr heretoforet blindness or even death. If a history is unavailable, a test for the osmolal gap (refer to on how osmolal gap is derived) is very useful. A high osmolal gap (10 mOsm/kg H20) indicates the presence of significant amounts of low molecular weight substances such as methanol. When methanol is metabolised, the osmolal gap returns to the normal and the anion gap increases due to formic acid arrangement which causes bicarbonate ions to decrease via the Henderson Hasselbach equation.A high serum methanol concentration of 35 mg/dL ( 0mg/dL), low serum bicarbonate level of 18mmol/L, low pH of 7.32 and a high anion gap of 20mmol/dL confirms Amareens diagnosis of metabolic acidosis cause by methanol poisoning.TreatmentsIn this case, Amareen is treated with an ethanol drip. This is because like methanol, ethanol uses alcohol dehydrogenase as its first stage of metabolism and that ethanol has a higher affinity for alcohol dehydrogenase than methanol in the ratio of 201 (8). Therefore when ethanol enters the bloodstream, they will competitively bind to alcohol dehydrogenase thus inhibiting the formation of formic acid. In a clinical setting, a target level of 100-150 mg/dl is used to saturate alcohol dehydrogenase with ethanol (20). However, ethanol can be a challenge to administer due to irregular rate of metabolism making a steady target level difficult to maintain and it can also cause intoxication (20).Amareen later receives fomepizole treatment after the ethanol drip was not so effective. This is a better treatment because fomepizole has an even higher affinity for alcohol dehydrogenase than methanol in the ratio of 80001 (21). This prevents methanol from being metabolised. The advantages of fomepizole are the ease of administration, long duration of effect and that it doesnt cause intoxication (22). However, fomepizole is very expensive and is less widely available (23).Due to both ethanol and fomepizole being ineffective in reducing the serum concentration of methanol in the body, haemodialysis was started. Haemodialysis is the most effective way to remove methanol and formic acid from the body (24). This works by passing blood from the body through a dialysis ma chine that contains a series of membranes to filter out unwanted substances and replenish essential minerals to the blood and then pumping blood back to into the body. The reason why haemodialysis was not immediately administered was probably due to it requiring a neck line which is very invasive and can result in multiple complications for Amareen who is only 5 years old.5. Osmolarity and OsmolalityOsmolality refers to the osmolar concentration of plasma per kilogram of solvent. Osmolality is measured using osmometers. Osmolarity on the other hand refers to the osmolar concentration of plasma per litre of solution. This value is calculated using a set formula from measured concentrations of Na+, K+, glucose and urea. The equation is 2Na+ + 2K+ + Glucose + Urea (all in mmol/L). use osmolality and osmolarity, the osmolal gap can be calculated which is the difference between the actual osmolality and the calculated osmolarity which normally lies in the range of 8-10 mOsm/kg (25).6. C hild AbuseThere are four main categories of child abuse (26). Physical abuse which involves bodily harm for example bruises, burns and fractures. Emotional abuse that involves persistent turned on(p) ill-treatment or neglect causing adverse effects on the childs emotional development. Sexual abuse by forcing a child to perform internal activity. This includes non-contact sexual activities such as producing child pornography. Lastly, negligence which is the failure of carers to provide the basic physical and psychological needs as well as management from harm to the child which results in an adverse effect on the childs health and development. An example would be protecting a child from serious substances which Amareens parents have failed to do.ReferencesNHS. Barts Health General surgery for patients NHS 2014 cited 2014 11 November. forthcoming from http//www.bartshealth.nhs.uk/our-services/services-a-z/g/general-surgery/for-patients/.College AC. Electrolyte Fluid Balance Austi n Community College 2014 cited 2014 11 November. Available from http//www.austincc.edu/apreview/EmphasisItems/Electrolytefluidbalance.html.Keener P. Okeanos adventurer Expeditions INDEX 2010 Indonesia-USA Deep-Sea Exploration Expedition Purpose 2014 cited 2014 11 November. Available from http//oceanexplorer.noaa.gov/okeanos/explorations/10index/background/edu/purpose.html.Droual R. The Urinary System Fluid and Electrolyte Balance Modesto Junior College 2014 cited 2014 11 November. Available from http//droualb.faculty.mjc.edu/Course%20Materials/Physiology%20101/Chapter%20Notes/Fall%202011/chapter_19%20Fall%202011.htm.Jones AW, Jonsson KA, Neri A. Peak blood-ethanol concentration and the time of its occurrence after rapid drinking on an empty stomach. J Forensic Sci. 199136(2)376-85.Zimatkin SM, Deitrich RA. Ethanol metabolism in the brain. Addiction Biology 1997. p. 387-400.Zakhari S. Alcohol metabolism and epigenetics changes. Alcohol Res. 201335(1)6-16.(IPCS) IPoCS. Methanol. E nvironmental Health Criteria 196. Geneva WHO 1997.Strmann K, Ryan MT. Alcohol-Related EmergenciesA New Look At An Old ProblemEmergency medicine Practice. 20013(9)9.Jacobsen D, McMartin KE. Antidotes for methanol and ethylene glycol poisoning. J Toxicol Clin Toxicol. 199735(2)127-43.Swartz RD, Millman RP, Billi JE, Bondar NP, Migdal SD, Simonian SK, et al. Epidemic methanol poisoning clinical and biochemical analysis of a recent episode. Medicine (Baltimore). 198160(5)373-82.Tephly TR. The toxicity of methanol. breeding Sci. 199148(11)1031-41.Martin-Amat G, McMartin KE, Hayreh SS, Hayreh MS, Tephly TR. Methanol poisoning ocular toxicity produced by formate. Toxicol Appl Pharmacol. 197845(1)201-8.Nicholls P. The effect of formate on cytochrome aa3 and on electron transport in the intact respiratory chain. Biochim Biophys Acta. 1976430(1)13-29.Alonso JR, Cardellach F, Lopez S, Casademont J, Miro O. century monoxide specifically inhibits cytochrome c oxidase of human mitochondrial res piratory chain. Pharmacol Toxicol. 200393(3)142-6.Fontanesi F, Soto IC, Barrientos A. Cytochrome c oxidase biogenesis new levels of regulation. IUBMB Life. 200860(9)557-68.Shah S, Pandey V, Thakore N, Mehta I. Study of 63 cases of methyl alcohol poisoning (hooch tragedy in Ahmedabad). J Assoc Physicians India. 20126034-6.Jammalamadaka D, Raissi S. Ethylene glycol, methanol and isopropyl alcohol intoxication. Am J Med Sci. 2010339(3)276-81.Sejersted OM, Jacobsen D, Ovrebo S, Jansen H. Formate concentrations in plasma from patients poisoned with methanol. Acta Med Scand. 1983213(2)105-10.Jacobsen D, McMartin KE. Methanol and ethylene glycol poisonings. Mechanism of toxicity, clinical course, diagnosis and treatment. Med Toxicol. 19861(5)309-34.Bestic M, Blackford M, vibrating reed M. Fomepizole a critical assessment of current dosing recommendations. J Clin Pharmacol. 200949(2)130-7.Hall TL. Fomepizole in the treatment of ethylene glycol poisoning. Cjem. 20024(3)199-204.Rathi M, Sakh uja V, Jha V. Visual blurring and metabolic acidosis after ingestion of bootlegged alcohol. Hemodial Int. 200610(1)8-14.Suki WN, Massry SG. Therapy of renal diseases and related disorders Springer 1991.Kapur G, Valentini RP, Imam AA, Jain A, Mattoo TK. Serum osmolal gap in patients with idiopathic nephrotic syndrome and severe edema. Pediatrics. 2007119(6)e1404-7.NICE. When to suspect child maltreatment. July 2009.