The Normal Reference Range for a Healthy Human - Case Study Example

Case Study Problem Name Lecturer Course Date Question 1 (18 marks) For each of the test results presented in the case study, are the figures within the normal reference range for a healthy human (you need to find and present a reference range for each test)?  Normal ranges are as follows: Plasma total [bilirubin] normal range is 3-25 μmol/L; 75μmol/L is above the normal value. Plasma AST normal range is 0-35U/L, 40 U/L is therefore above the normal value. Plasma ALT normal range is 7-56U/L, 58 units/ L is slightly above the normal range thus indicates an early onset of a pathological defect (Collins et al., 2016). Plasma GGT normal value is 0-30U/L, 50 U/L is above the normal range thus indicates an imbalance in the biochemical processes of the body. Plasma [ceruloplasmin] normal range is 200-600mg/L, 95mg/L is therefore below the normal range. Plasma [copper] normal range is 1.6-2.4 μmol/L; 7μmol/L is above the normal range thus an indicator of a disturbance in the biochemical balance (Bossolasco et al., 2017). Question 2 (30 marks) For each of the test results presented in the case study you should state what conclusion you draw from that test. If the test result is in the normal range, what does that tell you (you will need to consider the normal role of the enzyme/metabolite)? If the test result is not in the normal range, what does that indicate (again, consider the role of that enzyme/metabolite)? Plasma total [bilirubin] level is elevated. Elevation of bilirubin is an indicator of haemolysis from any cause. Bilirubin is elevated in poor erythropoiesis, breakdown of haemoglobin leading to increased bilirubin when haem is broken down (Shi et al., 2017). This is probably due to inflammation of the gall bladder, cholecystitis, or inflammation of the bile ducts, cholangitis. This elevation could also point to some inherited syndromes such as Gilbert Syndrome marked with unconjugated hyperbilirubinemia or Dubin Johnson Syndrome marked with conjugated hyperbilirubinemia (Acharya et al., 2016). Hyperbilirubinemia also indicate hepatitis infections that could be due to the viruses (HAV, HBV, HCV, HDV, HEV), autoimmune hepatitis or the metabolic disorders such as Wilson disease, hemochromatosis and alpha-1 antitrypsin deficiency. Plasma AST level is slightly above the normal range thus indicates a liver injury or damage to the muscles. It reflects infection of the liver with resultant poor biochemical substance flow. Plasma ALT is normally involved in the gluconeogenesis in glucose deficient states. These could be due to infection of the liver with a breakdown of the normal interplay between glucose uptake into the cells by insulin and release of glucose into circulation by glucagon hormone among other anti-insulin hormones (Kellum & Cerda, 2013). Its elevation indicates a compromise to this regulatory mechanism. Plasma GGT is elevated thus pints to a defect in the normal transport of metabolites in circulation (Collins et al., 2016). It indicates an increased transportation of the metabolites in the circulation. These metabolites could be products of drugs breakdown, chemicals, and compounds among other substances that are usually detoxified by the liver. They could even be metals or electrolytes in the circulation. Plasma ceruloplasmin level is very low. This indicates a decreased amount of copper in circulation due to either Wilson disease or Menkes disease or aceruloplasminemia. This indicates a nephrotic syndrome, hepatic encephalopathy, liver cirrhosis, intestinal malabsorption, malnutrition, among other liver diseases (Collins et al., 2016). The Wilson defects would be due to a mutation in the ATP7B genes while Menkes would be due to mutation of ATP7A gene. This would lead to accumulation of copper in the tissues while decreased in circulation thus a decreased ceruloplasmin level. Plasma [copper] is above the normal levels. This point to excess storage of copper in the tissues. The deposition of copper would be into tissues that are usually the liver causing jaundice, nausea and abdominal pain (Hoffmann et al., 2017). Increased deposition in the brain would lead to dystonia, fatigue, tremors, and difficulty walking. Question 3 (18 marks) Given the above results, what diagnosis would you make? How could you confirm this diagnosis (give some detail e.g. what sort of samples you would require, what test you would run, and what results would you expect if your diagnosis is correct). The diagnosis is as a result of a metabolic disorder called Wilson’s disease. Other tests, samples required and the expected results are as outlined below. Urine copper levels would be tested using the urine as the sample. In this experiment, a 24 hours’ urine of the patient would be collected. This would be elevated. The normal urine copper is in most cases, less than 0.6 μmol/L in 24 hours urine according to studies such as Alawi et al. (2016). In Wilson’s disease, the urine copper levels are elevated above 1.6 μmol/L/24hours urine. The hepatic copper would be determined in a specimen of a liver biopsy. This biopsy study would in normal situations indicate levels less than 250 μg/g dry weight. In Wilson’s disease, the levels of hepatic copper would be more than 250μg/g dry weight. The abnormality of the suspicion of elevated copper levels in the cerebrum would be performed by a study of a cerebral magnetic Resonance Imaging (MRI). Normally, the imaging would indicate a normal cerebrum (Schnabel et al., 2016). This observation is different with the case of Wilson’s disease. In this disease, the appearance would be abnormal. Because my patient is above 10 years, I would conduct a study to determine the presence of Kayser-Fleischer ring. These are diagnostic rings that are brown that in Wilson’s disease are deposited on the iris of the patient. The study of these rings is performed by the aid of a slit-lamp. Question 4 (24 marks) Describe the pathophysiology of the condition that you have diagnosed (i.e. what causes this disease? How does this lead to the disease symptoms?). Wilson’s disease is an inherited autosomal disorder caused by mutation in ATP7B gene that is responsible for conversion of apoceruloplasmin into ceruloplasmin leading to accumulation of copper due to defective excretion of copper into biliary canaliculi (Bisswanger, 2013). This build-up of copper into the canaliculi leads to toxic effect including the destruction of the mitochondrial membrane leading to damage of the cells. This then is followed by spillage of copper from the hepatocytes into the blood thus carried to other organs including the kidneys, brain, and red blood cells (Schnabel et al., 2016). This led to hepatitis-like symptoms including jaundice, abdominal pains. This was clinically illustrated by the elevated AST and ALT levels. Increased copper transportation into the circulation points to the cause of elevated GGT that normally functions to transport metabolites in the circulation and in this case increased copper transportation to the tissues of the cerebrum, kidneys, and the red blood cells. Increased deposition of copper into the tissues led to the decreased concentration of ceruloplasmin there was no coper transport just the deposition of copper into the tissues. When copper in circulation reaches the brain, it damages the lenticular nuclei. Through its oxidative damage to the brainstem, thalamus, cerebellum and cerebral cortex. It also leads to the damage of the astrocytes including the Opalski cells and the Alzheimer cells. These degeneration causes necrosis, breakdown of the glial cells and cystic changes. This led neurological symptoms. This would in the long run compromise brain functioning and subsequently lead to neural defects that were observed at the clinic. This led to dystonia, difficulty walking among other defects (Bisswanger, 2013). The deposition of copper in the kidney’s proximal convoluted tubule leads to Fanconism marked by bicarbonate in urine, glycosuria, proteinuria, amino aciduria and phosphates in urine. This led to the increased copper urine concentration. Deposition of copper would also occur in the iris of the patients after being carried through blood circulation and would result into Kayser Fleischer rings in the Descemet’s membrane of the cornea. While in the circulation, copper oxidative potential would breakdown the red blood cells and the subsequent breakdown of haemoglobin leading to haemolysis. This led to increased haemoglobin breakdown. The products are haem and globin. Globin is broken down into substituent amino acids and recycled (Devasena, 2015). Haem is then deprived of iron leading to carbon monoxide, and bilirubin production. This thus points to the reason for the elevated bilirubin. Question 5 (10 marks) Describe the treatment and/or management options that may be put in place for the patient. How do these strategies help to control or alleviate the disease symptoms? The management of Wilson’s disease involves measures and mechanism that alleviate the increased copper levels. These include treatments modalities that are described below. Restriction of the dietary copper intake. This helps to alleviate symptoms by decreasing the amount of copper ingested that could be in turn deposited in the tissues (Crook, 2013). This is achieved by restriction foods in copper which includes liver, shellfish, chocolates, nuts. Use of copper chelators. These drugs include penicillamine, triethylelentetramine. This treats the condition by chelating copper present in the tissues thus alleviating the symptoms. Ingestion of Zinc would reduce intracellular copper as it also chelates copper leading to decreased copper absorption thus control the amount of copper in the circulation. Liver transplant alleviates the symptom and is a curative therapy for the condition. It alleviates the symptoms from the neural damages, kidney damages, and deposition into the eyes (Bisswanger, 2013). References Acharya, G., Mehra, S., Patel, R., Frunza-Stefan, S., & Kaur, H. (2016). Fatal nonhepatic hyperammonemia in ICU setting: a rare but serious complication following bariatric surgery. 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