Clinical Biochemistry - Lec 1+2 - CHO - Pharmacy 5th Stage 2024 - 2025 PDF

Shared using Xodo PDF Reader and Editor Dr. Rasha Khalaf Pharmacy college- 5th stage 2024-2025 Lec1  Shared using Xodo PDF Reader and E...

Shared using Xodo PDF Reader and Editor Dr. Rasha Khalaf Pharmacy college- 5th stage 2024-2025 Lec1  Shared using Xodo PDF Reader and Editor A. Chemistry of CHO The main monosaccharide hexoses are reducing sugars. Naturally occurring polysaccharides are long- chain carbohydrates composed of glucose subunits Starch, found in plants, is a mixture of amylose (straight chains) and amylopectin (branched chains). Glycogen, found in animal tissue, is a highly branched polysaccharide  Shared using Xodo PDF Reader and Editor Functions of extracellular glucose The main function of glucose is as a major tissue energy source (glycolysis and citric acid cycle). The brain is highly dependent upon the extracellular glucose concentration for its energy supply; hypoglycaemia is likely to impair cerebral function or even lead to irreversible neuronal damage. This is because the brain cannot:  synthesize glucose,  store glucose in significant amounts,  metabolize substrates other than glucose and ketones – plasma ketone concentrations are usually very low and ketones are of little importance as an energy source under physiological conditions,  extract enough glucose from the extracellular fluid (ECF) at low concentrations for its metabolic needs, because entry into brain cells is not facilitated by insulin  Shared using Xodo PDF Reader and Editor Normally the plasma glucose concentration remains between about 4 mmol/L and 10 mmol/L, despite the intermittent load entering the body from the diet. The maintenance of plasma glucose concentrations below about 10 mmol/L minimizes loss from the body as well as providing the optimal supply to the tissues. Renal tubular cells reabsorb almost all the glucose filtered by the glomeruli, and urinary glucose concentration is normally too low to be detected by the usual tests, even after a carbohydrate meal. Significant glycosuria usually occurs only if the plasma glucose concentration exceeds about 10 mmol/L – the renal threshold.  Shared using Xodo PDF Reader and Editor How the body maintains extracellular glucose concentrations ((REGULATION) 1. Hormones concerned with glucose homeostasis Insulin Glucagon Somatostatin Other hormones 2. The liver Other organs 3. Systemic effects of glucose intake  Shared using Xodo PDF Reader and Editor Insulin Insulin is the most important hormone controlling plasma glucose concentrations. A plasma glucose concentration of greater than about 5 mmol/L acting via the glucose transporter 2 stimulates insulin release from the pancreas b-cell. These cells produce proinsulin, which consists of the 51-amino-acid polypeptide insulin and a linking peptide (C-peptide). Splitting of the peptide bonds by prohormone convertases releases via intermediates equimolar amounts of insulin and C-peptide into the ECF Shared using Xodo PDF Reader and Editor  Shared using Xodo PDF Reader and Editor Action of insulin 1. Insulin binds to specific cell surface receptors on muscle and adipose tissue, thus enhancing the rate of glucose entry into these cells. 2. Insulin-induced activation of enzymes stimulates glucose incorporation into glycogen (glycogenesis) in liver and muscle 3. Insulin also inhibits the production of glucose (gluconeogenesis) from fats and amino acids, partly by inhibiting fat and protein breakdown (lipolysis and proteolysis).  Shared using Xodo PDF Reader and Editor 4. The transport of glucose into liver cells is insulin independent but, by reducing the intracellular glucose concentration, insulin does indirectly promote the passive diffusion of glucose into them. 5. Insulin also directly increases the transport of amino acids, potassium and phosphate into cells, especially muscle; these processes are independent of glucose transport. 6.In the longer term, insulin regulates growth and development and the expression of certain genes. Shared using Xodo PDF Reader and Editor  Shared using Xodo PDF Reader and Editor Glucagon is a single-chain polypeptide synthesized by the a-cells of the pancreatic islets. Its secretion is stimulated by hypoglycaemia. Glucagon enhances hepatic glycogenolysis (glycogen breakdown) and gluconeogenesis.  Shared using Xodo PDF Reader and Editor Somatostatin This peptide hormone released from the D cells of the pancreas inhibits insulin and growth hormone release.  Shared using Xodo PDF Reader and Editor Other hormones When plasma insulin concentrations are low, for example during fasting, the hyperglycaemic actions of hormones, such as growth hormone (GH), glucocorticoids, adrenaline (epinephrine) and glucagon, become apparent Secretion of these so-called counterregulatory hormones may increase during: stress and in patients with acromegaly (GH), Cushing’s syndrome (glucocorticoids) or in phaeochromocytoma (adrenaline and noradrenaline ) and thus oppose the normal action of insulin.  Shared using Xodo PDF Reader and Editor 2. The liver The liver is the most important organ maintaining a constant glucose supply for other tissues, including the brain. It is also of importance in controlling the postprandial plasma glucose concentration. Portal venous blood leaving the absorptive area of the intestinal wall reaches the liver first, and consequently the hepatic cells are in a key position to buffer the hyperglycaemic effect of a high-carbohydrate meal glucagon or fat ‫يخلصني مَہטּ هاي الكميه الجبيرة يا يخزنة ع شكل‬  Shared using Xodo PDF Reader and Editor The entry of glucose into liver and cerebral cells is not directly affected by insulin, but depends on the extracellular glucose concentration. The conversion of glucose to glucose-6-phosphate (G6P), the first step in glucose metabolism in all cells, is catalysed in the liver by the enzyme glucokinase, which has a low affinity for glucose compared with that of hexokinase, which is found in most other tissues. Glucokinase activity is induced by insulin. Therefore, hepatic cells extract proportionally less glucose during fasting, when concentrations in portal venous plasma are low, than after carbohydrate ingestion. This helps to maintain a fasting supply of glucose to tissues such as the brain.  Shared using Xodo PDF Reader and Editor The liver cells can store some of the excess glucose as glycogen. The rate of glycogen synthesis (glycogenesis) from G6P may be increased by insulin secreted by the B- cells of the pancreas in response to systemic hyperglycaemia. The liver can convert some of the excess glucose to fatty acids, which are ultimately transported as triglyceride in very low-density lipoprotein (VLDL) and stored in adipose tissue.  Shared using Xodo PDF Reader and Editor Under normal aerobic conditions, the liver can synthesize glucose by gluconeogenesis using the metabolic products from other tissues, such as glycerol, lactate or the carbon chains resulting from deamination of certain amino acids (mainly alanine).  Shared using Xodo PDF Reader and Editor The liver contains the enzyme glucose-6-phosphatase, which, by hydrolysing G6P derived from either glycogenolysis or gluconeogenesis, releases glucose and helps to maintain extracellular fasting concentrations. Hepatic glycogenolysis is stimulated: 1. by the hormone glucagon, secreted by the a-cells of the pancreas in response to a fall in the plasma glucose concentration, 2. by catecholamines such as adrenaline or noradrenaline  Shared using Xodo PDF Reader and Editor During fasting, the liver converts fatty acids, released from adipose tissue as a consequence of low insulin activity, to ketones. The carbon chains of some amino acids may also be converted to ketones. Ketones can be used by other tissues, including the brain, as an energy source when plasma glucose concentrations are low.  Shared using Xodo PDF Reader and Editor Other organs The renal cortex is the only other tissue capable of gluconeogenesis, and of converting G6P to glucose. The gluconeogenic capacity of the kidney is particularly important in: 1. hydrogen ion homeostasis and 2. during prolonged fasting. Other tissues, such as muscle, can store glycogen but, because they do not contain glucose-6-phosphatase, they cannot release glucose from cells and so can only use it locally; this glycogen plays no part in maintaining the plasma glucose concentration Shared using Xodo PDF Reader and Editor  Shared using Xodo PDF Reader and Editor Ketosis  Shared using Xodo PDF Reader and Editor ketosis Adipose tissue triglyceride is the most important long term energy store in the body. Greatly increased use of fat stores, for example during prolonged fasting, is associated with ketosis. Mild ketosis may occur after as little as 12 h of fasting.  Shared using Xodo PDF Reader and Editor During fasting, when exogenous glucose is unavailable and the plasma insulin concentration is therefore low, endogenous triglycerides are reconverted to free non-esterified fatty acids (NEFAs) and glycerol by lipolysis. Both are transported to the liver in plasma, the NEFA being protein bound, predominantly to albumin. Glycerol enters the hepatic gluconeogenic pathway at the triose phosphate stage; the glucose synthesized can be released from these cells, thus minimizing the fall in glucose concentrations.  Shared using Xodo PDF Reader and Editor Most tissues, other than the brain, can oxidize fatty acids to acetyl CoA, which can then be used in the TCA cycle as an energy source. When the rate of synthesis exceeds its use, the hepatic cells produce acetoacetic acid by enzymatic condensation of two molecules of acetyl CoA; acetoacetic acid can be reduced to b-hydroxybutyric acid and decarboxylated to acetone. These ketones can be used as an energy source by brain and other tissues at a time when glucose is in relatively short supply. Shared using Xodo PDF Reader and Editor  Shared using Xodo PDF Reader and Editor lactic acidosis Lactic acid produced by anaerobic glycolysis, may either be  oxidized to CO2 and water in the TCA cycle OR be reconverted to glucose by gluconeogenesis in the liver. ‫هسه هنا الزم ازوي هاي العمليتني حتى اتخلص مَہטּ االكتك اسدوس بس تحتاج اوكسجني اذا ما‬ ‫عندي اوكسجني تتيجة لشوك لو مرض قلبي ما اكدر اسوي هاي العمليات فيصير الكتك يتراكم وهو‬ ‫شي مو زين‬ 27  Shared using Xodo PDF Reader and Editor The physiological lactic acidosis  During muscular contraction (exercise), glycolysis stimulated by adrenaline and supply energy by TCA the rate of glycolysis may exceed the availability of oxygen needed in TCA and glycolytic product then accumulate and produce 2 lactate, The lactate transport in blood to liver where it can used for gluconeogenesis, providing glucose for muscle ((cori cycle) This physiological accumulation of lactic acid is a temporary phenomenon and rapidly disappears at rest, when slowing of glycolysis allows aerobic processes to ‘catch up’. 28 Shared using Xodo PDF Reader and Editor 29  Shared using Xodo PDF Reader and Editor Pathological lactic acidosis during hypoxia may occur because: 1. - production is increased by an increased rate of anaerobic glycolysis. 2. Use is decreased by impairment of the TCA cycle or impairment of gluconeogenesis. 30  Shared using Xodo PDF Reader and Editor o Hypoxia increases plasma lactate concentration because: - The TCA cycle cannot function anaerobically, so oxidation of pyruvate and lactate to CO2 and water is impaired. - Anaerobic glycolysis is stimulated because the falling ATP levels cannot be regenerated by the TCA cycle under anaerobic conditions. The combination of impaired gluconeogenesis and increased anaerobic glycolysis converts liver from an organ that consumes lactate to one that generates large amounts of lactic acid. Sever hypoxia for following cardiac arrest cause marked lactic acidosis example. 31  Shared using Xodo PDF Reader and Editor Hyperglycemia and diabetes mellitus o HYPERGLYCEMIA may be due to: 1. Intravenous infusion of glucose-containing fluids 2. Sever stress (transient effect) such as trauma, myocardial infarction or cerebrovascular accidents. 3. Diabetes mellitus or impaired glucose regulation. 32  Shared using Xodo PDF Reader and Editor Diabetes Mellitus DM is caused by an absolute or relative insulin deficiency. It has been defined by WHO, on the basis of laboratory findings: - fasting venous plasma glucose concentration of 7.0 mmol/l(126 mg\dl) or more (more than one occasion in the presence of diabetes symptoms) - OR a random venous plasma glucose concentration of 11.1 mmol/l(200 mg\dl) or more. 33  Shared using Xodo PDF Reader and Editor Classification of DM I. Type 1 diabetes mellitus (insulin-dependent diabetes mellitus) Cause: Destruction of beta cells of pancreatic islets Consequence: Absolute deficit of insulin Present during childhood and adolescence Insulin therapy is essential because they are prone to develop ketoacidosis Most of these cases are due to immune-mediated processes . There is a form of type 1 diabetes called idiopathic diabetes mellitus that is not autoimmune mediated but is strongly inherited and more common in black and Asian people There is also LADA (Latent autoimmune diabetes of adults), sometime called slow-onset type 1 diabetes 34  Shared using Xodo PDF Reader and Editor Classification of DM II. Type 2 diabetes mellitus (non insulin-dependent diabetes mellitus) - The disorder ranging from mainly insulin resistance with relative insulin deficiency to a predominantly secretory defect with insulin resistance. - Insulin may sometimes be needed - Onset is most usual during adult life - There is familial tendency and an associated with obesity. 35  Shared using Xodo PDF Reader and Editor III. Other specific types of diabetes mellitus Genetic defect of beta-cell function M aturity-onset diabetes of the young (MODY): 1. MODY 1: mutation of hepatocyte nuclear factor (HNF4A) gene 2. MODY 2: mutation of glucokinase gene 3. MODY 3: mutation of HNF1A gene Some cases are thought to be point mutation in mitochondrial DNA associated with DM and deafness 36  Shared using Xodo PDF Reader and Editor III. Other specific types of diabetes mellitus Genetic defect of insulin action Type A insulin resistance (insulin receptor defect), Insulin deficiency due to pancreatic disease 1- Chronic pancreatitis 2- Pancreatectomy 3- Haemochromatosis 4- Cystic fibrosis Infections 1- Septicemia 2- Congenital rubella 3- Cytomegalovirus 37  Shared using Xodo PDF Reader and Editor III. Other specific types of diabetes mellitus Endocrinopathies Relative insulin deficiency, due to excessive GH (acromegaly), phaeochromocytoma, glucocorticoid secretion (Cushing’s syndrome) Drugs 1- Thiazide diuretics 2- Interferon alpha 3- Glucocorticoids 38  Shared using Xodo PDF Reader and Editor III. Other specific types of diabetes mellitus Rare form of autoimmune-mediated diabetes 1- Anti-insulin receptor antibodies 2- Stiff man syndrome, with high level of GAD ((glutamic acid decarboxylase)) autoantibodies Genetic syndrome associated with diabetes 1- Down’s syndrome 2- Turner’s syndrome 3- Klinefelter’s syndrome 4- Myotonic dystrophy 39  Shared using Xodo PDF Reader and Editor IV. Gestational diabetes mellitus Women at high risk for GDM including: previously have GDM that given birth to a high- birth weight baby, obese, family history of DM, high-risk ethnic groups (black or South Asian). 40  Shared using Xodo PDF Reader and Editor Screening at the earliest and, if normal, retested at about 24-28 weeks, as glucose tolerance progressively deteriorates throughout pregnancy. Fasting venous plasma glucose ≥ 7.0 mmol/l and/or random measurement ≥ 11.1 mmol/l. Six weeks post partum, the woman should reclassified with repeat test 41  Shared using Xodo PDF Reader and Editor  Impaired glucose tolerance (IGT) IGT :blood sugar levels are elevated but not elevated enough to warrant a diagnosis of diabetes Fasting venous plasma glucose concentration < 7.0 mmol/l 2 h after an oral glucose intake (OGTT), plasma glucose between 7.8 mmol/l and 11.1 mmol/l Some patients with IGT develop diabetes mellitus later Pregnancy IGT is treated as GDM because of the risks to the fetus. 42  Shared using Xodo PDF Reader and Editor Metabolic features of DM Hyperglycemia o If plasma glucose > 10.0 mmol/l, glycosuria would be expected High urinary glucose concentration produce osmotic diuresis and therefore polyuria. Cerebral cellular dehydration due to hyperosmolality, secondary to hyperglycemia, causes polydepsia Prolonged osmotic diuresis may cause excessive urinary electrolyte loss. 43  Shared using Xodo PDF Reader and Editor Metabolic features of DM Abnormal in lipid metabolism These may be secondary to insulin deficiency Lipolysis is enhanced and plasma NEFA concentration rise. In the liver NEFA converted to acetyl CoA and ketones or re- esterified to form TG and incorporated into VLDL which accumulate in plasma because lipoprotein lipase, which require insulin for optimal activity to catabolise VLDL HDL-cholesterol tend to be low in type 2 DM 44  Shared using Xodo PDF Reader and Editor Metabolic features of DM Chylomicronaemia may also occur if insulin deficiency is very sever Cholesterol synthesis increased with an associated increase in LDL As a consequent, patients with DM may show high TG, raised cholesterol and low HDL- cholesterol 45  Shared using Xodo PDF Reader and Editor Long-term effects of DM Vascular disease is a common complication of DM Macrovascular disease due to abnormalities of large vessels (coronary artery, cerebrovascular or peripheral vascular insufficiency). The condition probably related to alteration of lipid metabolism and associated hypertension. Microvascular disease due to abnormalities of small blood vessels particularly affects the retina (diabetic retinopathy) and the kidney (nephropathy). May be related to inadequate glucose control. 46  Shared using Xodo PDF Reader and Editor Long-term effects of DM Infections are also more common in diabetic patients, e.g. urinary tract or chest infections Diabetic neuropathy can occur Diabetic ulcer, e.g. of the feet, can lead gangrene and amputation. The joints can also affected Skin disorder; e.g. abscesses 47  Shared using Xodo PDF Reader and Editor Monitoring of DM 1. Glycosuria Defined as a concentration of urinary glucose detectable. Usually, the proximal tubular cells reabsorb most of the glucose in the glomerular filtrate. Glycosuria occur when the plasma, and therefore glomerular filtrate, concentrations exceed the tubular reabsorptive capacity. When plasma glucose concentration > 10.0 mmol/l A diagnosis of diabetes mellitus should never be made on the basis of glycosuria. 48  Shared using Xodo PDF Reader and Editor Monitoring of DM 2.Blood glucose 3.Glycated haemoglobin HbA1c is formed by non-enzymatic glycation of haemoglobin and is dependent on: 1- mean plasma glucose concentration 2- lifespan of the red cell Falsely low values may be found in patients with haemolytic disease. HbA1c gives a retrospective assessment of the mean plasma glucose concentration during the preceding 6-8 weeks 49  Shared using Xodo PDF Reader and Editor Monitoring of DM The higher HbA1c, the poorer the mean diabetic or glycaemic control. 4. Fructosamine Plasma fructosamine may be used to assess glucose control over a shorter time course than that of HbA1c (about 2-4 weeks). Fructosamine reflect glucose bound to albumin, which has a plasma half-life of about 20 days but is problematic in patients with hypoalbuminaemia. 50  Shared using Xodo PDF Reader and Editor Monitoring of DM 5. Blood ketones 6. Urinary albumin determination and diabetic nephropathy One of the earliest signs of diabetic renal dysfunction is the development of small amounts of albumin in the urine (microalbuminuria). Normoalbuminuria < 30 mg/day or < 20 µg/min. Microalbuminuria 30-300 mg/day or 20-200 µg/min. o Untreated microalbuminuria can progress to albuminuria (> 300 mg/day), impaired renal function and finally end-stage renal failure. 51  Shared using Xodo PDF Reader and Editor Monitoring of DM A random urine sample or timed overnight collection can be useful to assess urinary albumin excretion, although the standard test is the urinary albumin to creatinine ratio (ACR), which avoids a timed urine collection. ACR < 2.5 g/mol for male ACR < 3.5 g/mol for female 52  Shared using Xodo PDF Reader and Editor Acute metabolic complication of DM 1. Hypoglycemia This is probably the most common cause of coma seen in diabetic patients Hypoglycemia is most commonly caused by overadministration of insulin plus inadequate food intake, or taken excessive exercise. Overadministration of hypoglycemic medicine 53  Shared using Xodo PDF Reader and Editor Acute metabolic complication of DM 2.Diabetic ketoacidosis Insulin insufficiency triggers the following: Increase lipid and protein breakdown Enhanced hepatic gluconeogenesis and impaired glucose entry into cells The clinical consequence of diabetic ketoacidosis are due to: – Hyperglycemia causing plasma hyperosmolality – Metabolic acidosis – Glycosuria 54  Shared using Xodo PDF Reader and Editor Acute metabolic complication of DM Diabetic ketoacidosis 1. Vomiting water & electrolyte loss (increase fluid depletion)(extracellular depletion) shift of water out of the cellular compartment and sever cellular dehydration 2. Haemoconcentration & glomerular filtration rate cause uraemia due to renal circulatory insufficiency 3. The rate of hydrogen ions production exceeds the rate of bicarbonate generation, which buffer H+, lead to plasma bicarbonate falls. H+ secretion causes a fall in urinary pH. 55 Shared using Xodo PDF Reader and Editor 56  Shared using Xodo PDF Reader and Editor Acute metabolic complication of DM Diabetic ketoacidosis 4. Failure of glucose entry into cells & glomerular filtration rate may raise plasma potassium concentration, before treatment is started. 57  Shared using Xodo PDF Reader and Editor Acute metabolic complication of DM Hyperosmolal non-ketotic coma (HONK) (hyperosmolar hyperglycaemic state (HHS)) Insulin is present to some degree : it suppress fat breakdown lack of ketosis insulin is present to some degree : its effective is less than needed for effective glucose transport hyperglycemia glycosuria & polyuria body fluid depletion intracellular dehydration, which contribute to coma Hypernatraemia due to predominant water loss is more commonly found than in ketoacidosis. 58  Shared using Xodo PDF Reader and Editor Acute metabolic complication of DM Lactic acidosis Can cause a high anion gap metabolic acidosis and coma Other causes of coma in patients with DM - Cerbrovascular accident because of the increased incidence of vascular disease - Diabetic patients can have any other coma, e.g. drug overdose - Diabetic patients are also more at risk of diabetic nephropathy & renal failure & thus uraemia coma 59  Shared using Xodo PDF Reader and Editor Investigation of suspected diabetes mellitus Fasting or random blood glucose determinations. OGTT may be required Plasma glucose estimation if a patient presents with symptoms of DM or glycosuria or if there is strong family history. 60  Shared using Xodo PDF Reader and Editor Investigation of suspected diabetes mellitus DM is confirmed if one of the following is present: A fasting (at least 10 h) venous plasma concentration ≥ 7.0 mmol/l on two occasions or once with symptoms. A random venous plasma concentration ≥ 11.1 mmol/l on two occasions or once with symptoms. 61 Shared using Xodo PDF Reader and Editor 62  Shared using Xodo PDF Reader and Editor Investigation of suspected diabetes mellitus HbA1c > 6.5 % is diagnostic of DM, but this is not universally agreed as other factors, e.g. haemoglobin variants and erythrocyte lifespan may affect HbA1c levels. 63  Shared using Xodo PDF Reader and Editor Hypoglycaemia Define if plasma glucose is less than 2.5 mmol/l in a specimen collected into a tube containing an inhibitor of glycolysis, e.g. fluoride oxalate. Blood cells continue to metabolize glucose in vitro if specimen collected without such an inhibitor (the result of glucose concentration in whole blood will be approximately 1.0 mmol/l lower)—((pseudo hypoglycemia)). Symptoms: sweeting, tachycardia, faintness, and dizziness or lethargy may progress rapidly to coma and if untreated, permanent cerebral damage or death may occur. 64  Shared using Xodo PDF Reader and Editor Hypoglycemia Symptoms: sweeting, tachycardia, faintness, and dizziness or lethargy may progress rapidly to coma and if untreated, permanent cerebral damage or death may occur. 65  Shared using Xodo PDF Reader and Editor Hypoglycemia divided into: Hyperinsulinaemia hypoglycemia Hypoinsulinaemia hypoglycaemia Reactive (functional) hypoglycaemia 66  Shared using Xodo PDF Reader and Editor Hyperinsulinaemia hypoglycaemia Insulin or other drugs are probably the most common causes. Hypoglycaemia in diabetic patient may be caused by accidental insulin overdosage, by changing insulin requirement or by failure to eat after insulin has been given. 67  Shared using Xodo PDF Reader and Editor Hypoglycaemia due to exogenous insulin suppresses insulin and c-peptide secretion. Measurement of plasma c-peptide concentrations may help to differentiate exogenous insulin administration from endogenous insulin secretion, whether it is from insulinoma or following pancreatic stimulation by sulphonylurea drugs. c-peptide ‫منخفص سبب انسولني خارجي واذا مرتفع انسولني داخلي مَہטּ خالل ادويه او‬ ‫ورم‬ 68  Shared using Xodo PDF Reader and Editor Pancreatic tumor ( An insulinoma )is usually a small, it is benign primary tumour of the islet cells of the pancreas. In response to exogenous insulin, insulin antibody can form. Sometimes, insulin antibodies form despite the patient never having been exposed to exogenous insulin- autoimmune insulin syndrome (AIS). Insulin receptor antibodies may cause hypoglycaemia, although they sometimes lead to insulin resistance and hyperglycaemia. 69  Shared using Xodo PDF Reader and Editor Hypoinsulinaemia hypoglycaemia Endocrine Glucocorticoid deficiency/adrenal insufficiency Severe hypothyroidism Hypopituitarism Organ failure Severe liver disease End-stage renal disease Severe congestive cardiac failure 70  Shared using Xodo PDF Reader and Editor Hypoinsulinaemia hypoglycaemia Some non-pancreatic islet cell tumours Insulin-like growth factor (IGF)-2- secreting tumours, e.g. liver, adrenal, breast,Leukaemias, lymphomas 71  Shared using Xodo PDF Reader and Editor Reactive functional hypoglycaemia Idiopathic Post-gastric surgery Alcohol induced Miscellaneous causes Von Gierke’s disease (type 1 glycogen storage disease) Drugs, e.g. salicylates, quinine, haloperidol pentamidine, sulphonamides 72  Shared using Xodo PDF Reader and Editor Miscellaneous causes Von Gierke’s disease (type 1 glycogen storage disease) Drugs, e.g. salicylates, quinine, haloperidol pentamidine, sulphonamides 73  Shared using Xodo PDF Reader and Editor Investigation of adult hypoglycaemia 74