Case Study: Methanol Poisoning of a Child

Case Study methyl intoxicant Poisoning of a ChildIntroductionIn this PBL, we observe a case of m ethyl intoxicant poisoning in a child. We will scratch line define the unfamiliar term of tertiary wish marrow and restrain to understand acidulent base homeostasis in the body, the basis for wood spirit poisoning. and so we will look at how ethyl alcohol and wood spirit be metabolised in the body fol pocket-sizeded by how methyl alcohol poisoning actually field of studys. We will to a fault discuss how the osmolal gap is obtained victimization osmolality and osmolarity and functionly child abuse.Learning Objectives interpretation of unfamiliar terminologyAn overview of acid base homeostasis in the bodyHow ethanol and wood alcohol be metabolised in the bodyHow does wood spirit poisoning work atOsmolality and osmolarityChild abuse1. Unfamiliar term Tertiary care fondnessA tertiary care centre is where a patient goes to when principal(a) and secondary care occupy no n been able to adequately action the patient. Tertiary care centres are equipped with spiritedly trained impart and exaltedly dedicated medical equipment to cater to complex treatments 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 imputable to the fact that she was so young and suffering from methanol poisoning.2. Overview of acid base homeostasis in the bodyAcid base homeostasis is the statute of hydrogen ions. The luxuriouslyer the tightness of hydrogen ions, the lower the pH and wrong-doing versa. Acidic solutions have a full(prenominal) pH whereas alkaline solutions have a lower pH. The public 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(prenominal) than 7.45 results in alkalosis.Acid base balance has its basis in the Henderson-Hasselbal ch equation shown in Figure 2. If we rearrange the equation, we see that bi nose candyate and nose candy dioxide directly affects the acid base balance.Figure 2 Henderson-Hasselbalch Equation (3) there are three main moods in which the body controls the acid base balance. These three systems unremarkably work together. Firstly, there are physiological moderates, each of which consist of a weak acid and its base saltiness or a weak base and its base acid. Physiologic buffers move immediately within seconds to the change in pH in the body. These buffer systems occur in twain 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 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 enough to birth the pH back to its normal value, pulmonary compensation can guide on place in the lungs. This works by eliminating or retaining carbon dioxide. increase ventilation effort (hyperventilation) and decreased ventilation effort (hypoventilation) are the cardinal ways pulmonary compensation works. The changes in pulmonary compensation is fast within a few proceeding.The final compensatory mechanism, renal compensation in the kidney, starts when the previous two mechanisms have failed to regulate the pH level in the body. The kidneys maintain 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 respond to a change in acid base balance.The normal arterial course gas values for incomplete pressure of carbon dioxide is 35-45 mmHg/ 4.7 kPa-6.0 kPa and bicarbonate soaking up is 22-26 mmol/L. A change in the partial pressure of carbon dioxide or bicarbonate concentration from normal leve ls results in respiratory or metabolic disorders respectively. This together with acidosis or alkalosis refractory 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 quadruplet main acid base disorders and respective compensation mechanisms (4).In Amareens case, metabolic acidosis occurs. The major cause is the high production of formic acid which is not excreted quickly from the body. This has caused a decrease in the bicarbonate concentration overdue to H+ combining with bicarbonate. By the law of hand action using the Henderson- Hasselbalch equation, there is extra CO2 generated therefrom Amareen shows respiratory compensation via tachypneic breathing whereby the peripheral chemo receptors in the lungs are stimulated which stimulates the alveoli to turn in to exhale the excess CO2. The exhalation of CO2 would in most cases be enough to correct the metabolic aci dosis 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, unremarkably known as drinking alcohol, is metabolised primarily by alcohol dehydrogenase in the liver. Once ingested, ethanol is quickly clothed by the gastrointestinal booklet and small intestines with concentrations reaching at maximum 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 H2O by the Krebs cycle in the mitochondria. Ethanol can 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 Oxidativ e pathways of ethanol metabolism in the body (7)Methanol metabolismMethanol, commonly known as wood alcohol, can be absorbed by the body via inhalation, ingestion and skin exposure (8). In this item 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 by and by ingestion (8). Methanol is primarily metabolised in the liver. In the first step, 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 meth anol (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 methanol and not methanol itself is considered to be toxic. The severity of the toxicity correlates with the grade 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 exposit 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 chain of the mitochondria which results in the synthesis of adenosine triphosphate (16). Thus, by inhibiting cytochrome C oxidase, there would be significant reduction in the synthesis of ATP resulting in cell hypoxia leading to cell wounding and death (17, 18).The amount of formic acid in the blood is relative to the increase 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 con actual loss in chloride ions. Thus, a low serum bicarbonate level is a reliable index 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 comfy as a history was available from her parents stating that she had ingested methanol. This allowed doctors to treat Amareen quickly and powerful to prevent blindness or even deat h. 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 encumbrance substances such as methanol. When methanol is metabolised, the osmolal gap returns to the normal and the anion gap increases due to formic acid formation 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 bloods tream, they will competitively bind to alcohol dehydrogenase thus inhibiting the formation of formic acid. In a clinical setting, a head 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 posterior level difficult to maintain and it can also cause insobriety (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 crapulence (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, hae modialysis 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 machine 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 work out using a set formula from measured concentrations of Na+, K+, glucose and urea. The equation is 2Na+ + 2K+ + Glucose + Urea (all in mmol/L). Using osmolality and osmola rity, 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. Child AbuseThere are four main categories of child abuse (26). Physical abuse which involves bodily disparage for example bruises, burns and fractures. Emotional abuse that involves persistent aroused ill-treatment or neglect causing adverse effects on the childs emotional development. Sexual abuse by forcing a child to perform knowledgeable 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 supervision 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 dangerous substances which Amareens parents have failed to do.ReferencesNHS. 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