Clinical disorders of blood glucose control hypoglycaemia

Transcription

1 Clinical disorders of blood glucose control hypoglycaemia Students should be able to: Discuss the causes, clinical picture, diagnosis and immediate management of hypoglycaemia in babies and children Key case You are the medical officer on call one Sunday morning, when a 3 year old child is brought to hospital in a coma. Apparently the child was quite well yesterday. This morning, the family slept late. When the mother got up, she noticed that her child was unusually pale and quiet. Even before she was able to make him his breakfast, he vomited once and then became unconscious. The further history is as follows: His birth weight was 2.2 Kg at term. He has been quite a thin child all along but is otherwise well. The day yesterday was spent at a picnic, where he was very active and did not have time to eat much. When the family got home, he was so tired he was put to bed without supper. On examination, he is pale and clammy. His pulse rate is fast. During the examination he starts to wake up groaning. He smells faintly of acetone. A finger prick dipstick test shows the blood glucose to be 1.5 mmol/l. After an intravenous injection of glucose, he wakes up and seems to be normal. Control of Blood Glucose The glucose in the blood stream is the body s most important energy fuel, especially for red blood cells, brain and kidney cells. Only a few tissues can utilize other sources of energy to maintain cellular function. It is therefore very important that blood glucose must be maintained in the normal range. There is therefore a continuous supply of glucose to the blood stream even as it is being used for metabolic energy needs. The blood glucose level reflects the balance between processes that produce and increase blood glucose (absorption from the gut after food, or production from glycogen, fat and protein during fasting) and those that reduce it by the utilisation in body tissues. The metabolic balance is maintained by different mechanisms according to whether the patient is fasting or has just eaten. In the FED STATE, carbohydrate food in the gut is converted to monosaccharides and glucose and absorbed into the blood stream. The rising glucose level stimulates insulin secretion, this promotes uptake of glucose into the cells of muscle, liver, adipose tissue, where the unused energy is stored as glycogen or fat. The enzymes promoting glycogenolysis and gluconeogenesis are effectively switched off. In the FASTED STATE, the supply of glucose from gut absorption dwindles away and the counter-regulatory hormones glucagon, catecholamines and steroids respond to the declining blood glucose level. These act on glycogen, fat and proteins to increase glycogenolysis and gluconeogenesis. Free fatty acids and ketone bodies become additional sources of energy, but the aim is to restore and maintain blood glucose. It can thus be said that the body has homeostatic defence mechanisms to protect the blood glucose. Hypoglycaemia results when the blood glucose drops too low and reflects failure of adaptation.

2 Definition: A blood glucose level of less than 2.5 mmol/l (<2.2 in the neonatal period) What causes hypoglycaemia? 1) Too little glucose made available from food or stores Substrate deficiency Defective glucose production 2) Glucose used up too fast Hyperinsulinaemia Substrate Deficiency This refers to a lack of intake of food or glucose, or insufficient stores to maintain glucose during fasting. Small for gestational age babies have not grown sufficiently during pregnancy and are born with very small reserves Protein energy malnutrition: The food intake of such children is insufficient to maintain proper glycogen stores or muscle Chronic diarrhoea. Such patients commonly have inadequate absorption and become malnourished Acute starvation. The glycogen reserves are exhausted Severe illness with decreased intake. This is equivalent to starvation plus increased energy requirements because of the illness state Ketotic hypoglycaemia A condition of small stores because of low birth weight and relatively poor growth in which children (most commonly boys) aged about 2 4 years develop hypoglycaemia and ketosis on exaggerated fasting. Defective glucose production This refers to an inability to make glucose even though stores of glycogen, fat and protein may actually be available. Such patients have inherited or acquired diseases involving hormones, enzymes, or the integrity of the liver cells where glucose is produced. Defects of glycogenolysis. Enzyme blocks in the conversion of glycogen to glucose. Glycogen storage diseases. Defects of gluconeogenesis. Large number of disorders involving endocrine control (anterior pituitary deficiencies) and enzyme pathways in intermediary metabolism. Liver cell pathology : Hepatic failure (eg cirrhosis, fulminating necrosis) or hepatotoxins such as Impila, Alcohol, salicylate intoxication, Jamaican Vomiting Sickness. Idiopathic causes (undefined or unknown)

3 Increased utilisation of glucose : Hyperinsulinaemia Infant of diabetic mother: Diabetes mellitus during pregnancy may result in the fetus being exposed to a high blood sugar for much of the time. This means that the fetal pancreas is stimulated to respond to the high blood glucose and increases the fetal insulin production. As a result, the fetus grows excessively fast because of the growth-promoting effect of insulin (anabolic). As the baby is delivered, the maternal glucose supply through the placenta is cut off, but the baby s insulin supply is still high. As a result, the baby can develop hypoglycaemia within a few hours after birth. Erythroblastosis fetalis: The condition of rhesus blood group incompatibility and severe haemolytic anaemia developing in utero is associated with hyperplasia of the pancreas and excess insulin production. Beckwith Syndrome: A genetic condition in which faulty gene action results in tissue overgrowth, organ enlargement and excess insulin production. Beta cell hyperplasia: The beta cells of the pancreas multiply too rapidly and produce too much insulin. Insulin-producing tumours of the islet cells can be benign or malignant Overtreatment with insulin or oral hypoglycaemic agents. The latter serve to release insulin from the pancreas. Risks of hypoglycaemia Particularly important in neonates and young infants because of the developing brain of that age. Symptomatic hypoglycaemia in young infants carries a high risk of permanent brain damage. This is a preventable cause of brain damage. In all patients, hypoglycaemia which is severe and prolonged enough will cause coma and convulsions and may lead on to brain damage and subsequent complications including epilepsy. Symptoms of hypoglycaemia These depend to a degree on the rate of fall and level of blood glucose. Two main groups of symptom complexes are seen: 1. Sympathetic stimulation Due to an acute fall of the blood glucose : Pallor, sweating, abdominal pain, sense of hunger (hunger pains), tachycardia and palpitations. Note that a patient whose blood glucose is falling gradually may not exhibit these symptoms. This applies also to patients who are very ill and whose stress response is already maximally active: such a patient will not show the sympathetic effects of hypoglycaemia and can then become unconscious without any warning. 2. Neuroglycopaenic (Brain cell glucose deprivation) Due to very low blood sugar and insufficient or no other energy substrate: deranged cerebral metabolism with delirium, confusion, coma and convulsions. Neonates These have immature expression of symptoms and may present with very non-specific signs including apnoea attacks (stopping breathing), strange changes in posture or breathing, in addition to convulsions and coma. It may be difficult to recognize any symptoms of hypoglycaemia at all. Recognition of hypoglycaemia It is essential to remember the circumstances that lead to hypoglycaemia and to be pro-active in looking for it before it leads to symptoms. Hypoglycaemia is a preventable cause of brain damage, and therefore we should not allow it to occur or go unnoticed, especially in circumstances where it might be associated with nonspecific or subtle symptoms for some time before it leads to convulsions. In the following situations it is imperative to monitor the blood glucose regularly in order to identify hypoglycaemia and treat it as early as possible:

4 Neonates Before feeding is established. Neonates have small glycogen reserves and cannot tolerate fasting. This is particularly important in low birth weight (<2.5 Kg) premature or small for dates babies. When critically ill for whatever reason. Such babies have the additional problems of increased requirements for energy and poor intake because of the disease. All patients All seriously ill patients who are not feeding may have used up glycogen reserves and become hypoglycaemic. Severely malnourished patients have low glycogen stores. Such patients commonly show no additional symptoms apart from their severely debilitated state and may develop hypoglycaemic coma or convulsions without warning. Sudden onset of coma or convulsions. The other symptoms of hypoglycaemia may have been missed. Diagnosis and Management of Hypoglycaemia Bedside test strip with a drop of fingerprick blood (eg Dextrostix). This can be confirmed with a formal blood sample for glucose sent to the laboratory. A low reading on a test strip done correctly is however sufficiently accurate to require action even if a blood glucose may be sent for confirmation. The essential message is not to waste time. Treat the hypoglycaemia: Give glucose : 1 g/kg body mass oral or IV injection (the latter when coma or convulsion is due to hypoglycaemia). This is equivalent to 10 ml/kg body mass of a 10% solution, or 2 ml/kg body mass of a 50% solution. Identify the cause. Consider the patient s history, circumstances and any additional knowledge from examination or investigation findings. Treat or remove the cause if it can be identified; plan to investigate it if a cause is not obvious. Confirm that the blood glucose is corrected and maintained. Repeat the test strip blood glucose in 1 hour and monitor regularly thereafter. Solution to key case I : This 3 year old boy was a small-for-dates child (growth retarded) with a body mass well below expected for his gestational age at birth. He had small glycogen and fat stores at birth and has not really developed better stores (stayed thin). On the day before, he had used up more energy than normal by the active playing at the picnic, and he had eaten less than normal. On the Sunday morning, breakfast was delayed. His glycogen reserves had been exhausted. The declining blood glucose caused the stress response with catecholamine mediated vasoconstriction (pale and clammy, tachycardia). He then developed ketosis as a response to intracellular starvation. Neuroglycopaenia resulted in coma, but gluconeogenesis occurred to let the blood glucose rise spontaneously and help him to start waking up. After intravenous glucose he woke up completely, but he could also have been given some sugar water, honey etc. After this, he needed his breakfast rather urgently to maintain his blood glucose. The breakfast should preferably supply not only carbohydrate but some fat and protein also. This is the picture of Ketotic Hypoglycaemia

5 Diabetes mellitus in children Students should be able to: Discuss diabetes mellitus in children under the following headings The differences between type I and type II diabetes Causes, pathogenesis and onset of type I diabetes Symptoms and signs of diabetes in children Complications and principles of control Key Case : Mrs C is very worried about her 9 year old son. He seems to have lost a lot of weight over the last 2 weeks although he has been eating very well. Last week she took him to the doctor because of flu-like symptoms and received a prescription for an antibiotic. Over the last few days he has started to complain of abdominal pain. Yesterday the teacher sent him home from school because he felt weak. Overnight he has started to vomit and now is extremely drowsy. On examination he is drowsy, seemingly with a depressed level of consciousness. He has deep sighing respirations and there is a strong smell of acetone on his breath. He is dehydrated and seems to be very thirsty. His pulse rate is 120/minute. His blood pressure is 90/60. His weight is only 19 kg. A urine specimen is obtained and shows Glucose 3+ and ketones 3+. A fingerprick glucose reading is 17 mmol/l. Diabetes mellitus in children Diabetes is caused by 2 main mechanisms: Too little insulin : Type I diabetes : found in children as well as adults Too little insulin effect although insulin is present: A problem of the number or function of the cell receptors for insulin: Type II diabetes : found mainly in adults. In children, diabetes is more commonly type I, although the increasing rate of obesity in children is also associated with an increasing number of type II diabetes cases. Type I Diabetes mellitus This is considered to be an auto-immune disorder, in which the body starts making antibodies against its own tissues for some reason and so progressively destroys those cells. In the case of diabetes, the auto-immune attack is directed against the beta cells of the islets of Langerhans. The body starts making antibodies against the islet cells or against insulin; these can be measured. In auto-immune disorders, the condition is brought on by a combination of 2 sets of circumstances: A genetic predisposition: commoner in certain families Environmental factors In type I diabetes, the following factors are operative: Diabetogenic gene linked to the main histocompatibility factors. There is a higher risk of diabetes in persons carrying the HLA DR3 or DR4 tissue types.

6 The environmental factors are not always readily apparent, but virus infections with mumps or enteroviruses play a part, as do a number of toxins. The effect of such infection- or toxin-induced damage is to expose antigenic components of the cells to circulating immune cells and induce the development of auto-antibodies. After the patient has started to produce insulin or islet cell antibodies, there is a progressive reduction in the total number of insulin producing cells, the beta cell mass. This leads to a progressive decline in the amount of insulin being secreted. The first abnormality to be identified is a state of carbohydrate intolerance in response to stress. In this situation, the patient s blood sugar rises too high in response to a challenge such as a stressful situation. During such a period (eg fever) the patient may actually show glucose in the urine. As the secretion of insulin gets less, the patient s blood glucose rises too high after a meal, and then finally there is just not enough insulin for daily requirement and the patient is now considered diabetic. This state is commonly precipitated by an intercurrent infection, which places an additional burden on the system. At this stage, symptoms will develop. The sequence and pathophysiology of the symptoms and signs is depicted in the diagram below: Type I diabetes mellitus: Pathophysiology of symptoms and signs Insulin Deficiency Consequences Intracellular Glucose Deficienccy Plasma Glucose Elevated Deficient A.T.P. production in C.A.C. Counter-regulatory Hormones stimulate Gluconeogenesis Electrolyte loss in urine Osmotic Diuresis Protein catabolism Fat catabolism Ketosis Polyuria Weakness Coma Wasting Polyphagia Acidosis Dehydration Thirst Type I diabetes has been termed a state of starvation in the midst of plenty. The starvation refers to the state of intracellular glucose depletion which is the reason for the catabolic state, wasting, ketogenesis and accelerated gluconeogenesis seen in this condition. The plenty on the other hand is the state of hyperglycaemia. Insulin deficiency means that glucose does not enter the cells for metabolism and stays in the blood stream. The hyperglycaemic state is responsible for the osmotic diuresis with resultant polyuria, dehydration, thirst, electrolyte loss and acidosis. It is very common for the symptoms of acute onset diabetes to have been present for a very short time only. Untreated, the condition progresses rapidly to ketoacidosis, coma and death.

7 Diagnosis Not difficult. Even if you don t think of it, do the blood sugar! This applies to the diagnosis of hypoglycaemia also. If the blood sugar is high, check the urine: the presence of glucose and ketones together equals diabetes. (Stress hyperglycaemia does not have ketones, and starvation ketosis does not have glycosuria.) Glucose Tolerance Tests are not usually necessary in children with type I diabetes. Management There are 2 phases of management: the stage of acute ketoacidosis, and the maintenance programme of longterm care. In ketoacidosis, the following principles apply: Insulin, to allow glucose to enter the cells and correct hyperglycaemia, ketosis and catabolism; Fluids and electrolytes to correct the dehydration, acidosis and deficits of a variety of electrolytes. Once the patient is back in a homeostatic state, the maintenance phase must begin. To achieve a near-normal state as possible, there has to be a balance between Insulin requirements Energy and glucose (food) intake Energy expenditure (exercise) This requires knowledge, acceptance and commitment on the part of the patient and the family. With the right training and support, it is possible for diabetic children to live normal lives.