Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
بسم هللا الرحمن الرحيم Faculty of Medicine Alexandria University Diabetes Unit & Clinical Pathology& Biochemistry Departments Clinical Scenario Prepared by Staff members of Diabetes, Metabolism & Clinical pathology and Biochemistry Departments Faculty of Medicine Alexandria University By the end of this ILA session , the students will be able to: 1-Recognize the clinical features of a common health problem among the Egyptian population, which results primarily from disturbance in the metabolism of Glucose 2-Apply the basic biomedical sciences studied in module II to explain the clinical features of these diseases. 3-Identify the relation between some of the common laboratory investigations used in diagnosis of the condition and the biochemical structures and processes already studied. Clinical Scenario Hoda is 48 years old lady with no family history of any serious conditions, except her father has diabetes mellitus. In the past few weeks, she had been experiencing increased urination, day & night, unusual thirst, and she started to feel weak and tired more rapidly than usual. Although she was eating more than usual, she now was losing weight . Hoda went to the primary health care doctor in her territory. The primary health care doctor took proper history from Hoda, and did complete physical examination. The doctor confirmed from the history that Hoda has now increasing urination , thirst , and loss of weight although she was feeling more hungry and eating more food The doctor also asked about the previous history of any diseases as well as the social status and habits Past History: •Appendectomy in 1992. No chronic illnesses. Social History and Habits: •Hoda is a house wife, she has 3 grown up children. •During the last few years, she spent most of her time watching TV & chatting with friends over the phone •She takes no medications, nutritional supplements or herbal remedies. Physical Examination •Pulse : 76 beats/min. (regular) •Blood pressure : 140/80 mm/Hg. •Body weight : 98.5 kg. •Height : 1.6 m •The rest of the examination including : Head and neck , Chest, abdomen and CNS were normal. Assess the anthropometric measures using what you learnt in nutrition module The doctor did a bedside test and said: Mrs. Hoda: The test result is abnormal and you will need some more investigations 1. Which of the following laboratory tests has the doctor conducted? • Stool analysis. • Urine analysis. • Complete blood count Urine samples used for detection of glucose 1- Early morning sample: The first sample the patient produces on waking up. It is a concentrated sample, therefore it is suitable for detection of glucose. 2- Random sample: A sample produced at any time during the day. Disadvantage: The kidney varies the composition of urine during the day according to water, salt & protein intake as well as metabolic status. Therefore this sample may be diluted and not very reliable. It gives a good positive but a poor negative test. Urine Reagent Strips Plastic strips containing dry reagents required for the enzymatic detection of glucose. In presence of glucose in the sample, a colour develops and its intensity changes according to the amount of glucose present. The strip is dipped briefly in urine. After 30 seconds, the colour which develops on the test strip is compared to the colours on the chart present on the box of strips. The matching colour is taken as the correct result. Clinical Scenario The doctor told her that the urine sample contains 3+ glucose which is not a normal finding . He said : We need to find out why there is glucose in the urine so we need to check your blood glucose level Urine strips are specific for glucose, i.e. they do not give a colour reaction with any substance except glucose. However, this is not an accurate quantitative test, In addition, people with high blood glucose levels may have a high renal sugar threshold and therefore glucose may not be excreted in urine Random Blood Glucose If you take the sample in the clinic by your self , then you should sent it immediately to the lab and test should be done done as quickly as possible . Otherwise, glucose level in the sample will decrease due to glycolysis which continues in vitro ( in the blood of the patient while outside his body) . We can collect the blood sample of the patient in specific Tubes containing sodium fluoride which helps to inhibit glycolysis and preserve glucose. Floride Tubes Plain Tubes After the doctor received this Glucose measurement he told Mrs Hoda that the result is high and this might mean that she has a common disease called Diabetes mellitus. He continued : thus ,we need to confirm the diagnosis. So ,I want you to go home , take your dinner at 10 pm , do not eat or drink any thing afterwards except enough water (water contains no calories). Then go to the lab at 8 am for other measurements Hoda went to the lab next day morning with the following request : •Fasting blood glucose •2 hours post oral glucose load test Fasting Plasma Glucose Blood sample for fasting plasma glucose is obtained after 8-12 hours fasting. The patient should drink water freely during this period so as to be well hydrated. Glucose load: 75 grams glucose dissolved in 300 mL water.The patient drinks this over a period of 5 minutes. A blood sample is taken 2 hours later. Laboratory results for Mrs. Hoda : •Fasting plasma glucose: 194 mg/dL. Reference range : 70 – <100 mg/dL •2-hours post load plasma glucose: 266 mg/dL. Reference Range : less than 140 mg/dL Hoda went back to the treating Doctor with the results. He told her that the results confirmed that she has diabetes and he started to explain the disease The doctor explained to Hoda that the diagnosis of diabetes mellitus is based on symptoms of hyperglycemia like what she has, plus the results of blood glucose tests: The laboratory results which make the doctor suspect diabetes are: • Fasting plasma glucose ≥ 126mg/dl • 2-h post oral glucose load test: blood glucose ≥ 200 mg/dl . • Random plasma glucose ≥ 200 mg/dl. Note to the Physician: If one of these tests is positive, it must be confirmed by another positive test on the subsequent day in order to diagnose diabetes mellitus. 1.What is hyperglycemia? 2.Why was there Hyperglycemia in this patient? 3.Explain why there is increased urination (polyuria) with this high blood glucose? 4.Why Hoda had increased appetite (polyphagia) despite high glucose levels? 5.Discuss normal glucose metabolism 6.Suggest the possible alterations in glucose storage and break down that might occur in this clinical problem . 1. 2. A. B. C. D. INSULIN DEFICIENCY: decreases uptake of glucose by cells. insulin dependent enzymes are less active Net effect: inhibition of glycolysis Inhibition of glycogenesis (glycogen synthesis) stimulation of gluconeogenesis Stimulation of glycogenolysis (glycogen degradation) INSULIN Glucose uptake by the tissues GLUCAGON Breakdown of tissue proteins Glycogenolysis Gluconeogenesis Hepatic output Of glucose HYPERGLYCEMIA Explain why there is increased urination (polyuria) with this high blood glucose? When the blood glucose levels exceed the renal sugar threshold glucose is excreted in urine (glucosuria) Due to the osmotic effect of glucose, more water accompanies glucose excretion Polyuria (increase in volume of urine excretion) When the blood glucose levels exceed the renal sugar threshold glucose is excreted in urine (glucosuria) osmotic effect of glucose Polyuria (increase in volume of urine excretion) water accompanies glucose excretion To compensate for the water loss Thirst centre is stimulated More water is is taken (polydepsia: always thirsty, drinks a lot) Why Hoda had increased appetite (polyphagia) despite high glucose levels? Although the blood glucose level is high but glucose is not taken up by the cells due to insulin deficiency therefore the cells are starved The patient will take more food (polyphagia) to compensate for the loss of glucose and also loss of protein Although the blood glucose level is high BUT BUT glucose is NOT taken up by the cells due to insulin deficiency the cells are starved The patient will take more food (polyphagia) to compensate for the decrease of glucose and ATP intracellulary Discuss normal glucose metabolism GLUCOSE GLUCOSE + Insulin glycolysis + Pyruvate + PDH ACETYL COA MITOCHONDRIA CITRIC ACID CYCLE ATP GLUCOSE -6- PHOSPHATE 1)OXIDATION a) For energy production (glycolysis & Krebs cycle) b) For production of pentose P and NADPH (HMS) 2) Conversion to other hexoses: Fructose, galactose 3)Conversion to non essential amino acids. 4)Storage in the form of glycogen or fats. c) For production of uronic acid. Biological effects of insulin PATHWAY Key enzyme Action of insulin on the enzyme Glycolysis Glucokins Stimulation dephosphorylation e of the enzymes PFK-1 Pyruvate kinase Gluconeo- *Pyruvate Inhibition carboxylase genesis *PEPCK *F1,6 diphosphatas e *Glucose 6 phosphatase Dephosphorylation of the enzymes Direct Overall effect effect Hypoglycemia Hypoglycemia Biological effects of insulin PATHWAY Key enzyme Action of insulin on the enzyme Glycogen synthesis Activation Glycogen synthase Direct effect Glycoge dephosphorylatio n storage n Overall effect Hypoglycemia of the enzymes Glycogen degradation Glycogen phosphorylas e Glycoge dephosphorylatio n storage n Inactivation of the enzymes Hypoglycemia In Diabetes Mellitus all these effects are reversed because INSULIN A. B. C. D. GLUCAGON inhibition of glycolysis Inhibition of glycogenesis (glycogen synthesis) stimulation of gluconeogenesis Stimulation of glycogenolysis (glycogen degradation) A. B. Suggest the possible alterations in glucose storage and break down that might occur in this clinical problem. Inhibition of glycogenesis (glycogen synthesis) Stimulation of glycogenolysis (glycogen degradation) During digestion, food is broken down into basic components, such as fatty acids from lipids, amino acids from proteins and simple sugars from carbohydrates. All of these nutrients can be processed by of the liver into one type of simple sugar, glucose, which then enters the blood stream. After digestion, glucose passes into the bloodstream, where it is used by cells for growth and energy. For glucose to get into cells, insulin must be present. Insulin is a hormone produced by the pancreas, a large gland behind the stomach. When normal people eat, the pancreas automatically produces the right amount of insulin to move glucose from blood into our cells. In people with high blood glucose, when they eat, the pancreas either produces little or no insulin, or the cells do not respond appropriately to the insulin produced (or both) => glucose builds up in the blood, overflows into the urine, and passes out of the body in urine => body loses its main source of fuel even though blood contains large amounts of glucose. In the early stages of high blood glucose, there are no symptoms until blood glucose levels exceed the "renal threshold" and glucose appears in the urine. When the "renal threshold" for glucose (a blood glucose level of about 180 mg/dL), is exceeded for a significant portion of the day, the patient will have the classic symptoms of hyperglycemia: excessive urination (polyuria) with consequent thirst and need to keep drinking (polydipsia). The loss of calories, due to the glucose loss in urine, will lead to weight loss, and often a compensatory increase in appetite (polyphagia). The weight loss primarily is due to loss of muscle mass with conversion of amino acids into glucose, as a result of increase gluconeogenesis. Persistent hyperglycemia can draw water into the eyes and cause visual blurring. Clinical Scenario The doctor continued to talk to Hoda about her illness. He said: Diabetes is very common in Egypt. There are about 8 million Egyptians that are diabetic, but a third of them don’t know they have it. Egypt is one of the top ten countries all over the world that have large number of diabetics. Your disease has some genetic predisposition. But the main reasons that made it manifest is the increased weight you had and the style of life you were adopting in the last few years. You were not doing any regular exercise and you were living a sedentary life: حياة مستقرة تتميز بقلة الحركة This type of diabetes is easily controllable through exercise, proper nutritional habits and diet control , with weight loss. In addition we might need to give a drug called Hypoglycemic drug . Can you explain how exercise, and weight loss can help the diabetic patient to control the high blood glucose? Diet: Daily caloric intake: Carbohydrates : 50 – 60% Proteins : 15 – 20% Fats : 25 – 30% Meals should be high in fibers and low in simple sugars and saturated fats Diet should be balanced, and distributed throughout the day with the major 3 meals and 2-3 snacks Carbohydrates (CHO): 1- Simple CHO: Sucrose, Honey, Jam, soft drinks, fruit drinks 2- Complex CHO: Rice, bread, cereals, dried beans, fruits, vegetables, dentils and legumes. • • • Proteins Examples: Lean meat, fish, chicken without skin, milk, egg, & seafood. Fish should be eaten more often and skin should be removed from chicken. Boiled foods are better than fried foods. Fats 2 types: saturated & unsaturated: a-Saturated fat: Solid at room temperature. Examples: Butter, fat in meat and animal products such as hamburger, cheese, coconut oil, and palm oil These should not exceed 7% of the total energy from fat group. b-Unsaturated fat: Monounsaturated: Olive oil, Peanut oil Polyunsaturated: Soya bean, Corn, Sunflower oils. & Exercise • Lowers blood sugar and • Increases sensitivity to insulin • Lowers blood pressure. • Helps to loose weight and maintain weight • Improves lipid profile Aerobic exercise (brisk walking) is generally recommended Exercise should be done regularly on daily bases at 30 min/day at least 5 times a week Start slowly and gradually increase the amount of exercise