Answer: The two main groups of reactions are:

• Anabolism (anabolic): building up complex molecules from small ones
• Catabolism (catabolic): breaking down nutrients to provide energy for the reactions of anabolism

Disorders of either of these types of reaction can cause a range of disturbances of physiology and anatomy including: growth and developmental delay, neuromuscular symptoms and congenital brain malformation, autonomic symptoms, jaundice, change in urine colour and unusual odours in body fluids, organomegaly and eye changes. There are a wide range of tests which can be carried out to aid achievement of the specific diagnosis.

Answer: Metabolic syndrome consists of a complex range of disorders. Someone is identified as having this condition if they have: central obesity (i.e. waist circumference outwith the limits set for the specific ethnic group) and at least two of the following: raised triglycerides, reduced HDL cholesterol, raised blood pressure, raised fasting plasma glucose (FPG). It is linked with cardiovascular changes and significant insulin resistance thus predisposing to diabetes. These conditions can have a significant influence on how the individual can function and the support needed by their family.

Answer: The overall rate of body metabolism is determined by the level of secretion of the thyroid hormones. They are important in regulating lipid, cholesterol and glucose metabolism in the liver and, thus, influence the development of metabolic syndrome. They regulate mitochondrial function (i.e. energy homeostasis) and fatty acid metabolism. The two main conditions which can occur are:

• Hypothyroidism: decreased thyroid hormones cause slowing of metabolism with bradycardia, fatigue, weight gain, cold intolerance, decreased exercise capacity, muscle weakness, constipation, depression and menstrual irregularities. It is common in clinical practice.
• Hyperthyroidism: raised levels of thyroid hormones in the blood result in increased anabolism and metabolic rate, with raised heat production leading to heat intolerance. The response to autonomic stimulation is increased.

Answer: Blood glucose levels are controlled by four types of cell in the pancreas. DM is a disorder of carbohydrate, fat and protein due to inadequate insulin secretion. It can occur due to:

• an absolute or relative insulin deficiency which may be due to:
  • impaired release of insulin
  • production of inactive insulin
• insulin resistance which may be due to:
  • inadequate or defective insulin receptors or post-receptor regulation
  • insulin destroyed before it can carry out its action.

Type 1 DM is due to an absolute lack of insulin causing hyperglycaemia and glycosuria with the following effects: polyphagia, weight loss, ketonuria, fatigue, polyuria, polydipsia. Insulin by injection must be administered.

Type 2 DM is due to an inadequate secretion of insulin, largely related to genetic factors and obesity, limiting the amount of glucose entering the cells and being metabolised. Oral hypoglycaemic drugs are usually used in controlling this condition.

Answer: The complications of DM fall into two main categories: acute and chronic.

• The acute complications are threefold: two related to high blood glucose and one to low blood glucose levels. These are:
  • Diabetic ketoacidosis (DKA) in type 1 DM. The metabolic changes are hyperglycaemia (which develops as glucose cannot enter the cells), ketosis and metabolic acidosis. Ketosis occurs as fat is metabolised for energy and metabolic acidosis happens due to the build-up of ketones.
  • Hyperosmolar hyperglycaemic non-ketotic syndrome (HHNKS) occurs in type 2 DM with hyperglycaemia, hyperosmolarity, dehydration and absence of ketones (limited insulin present prevents conversion of fats and proteins to ketones) occurring. Dehydration develops because of glycosuria; as plasma volume with increased serum osmolarity resulting in dehydration, polyuria and polydipsia and may cause weakness and neurological signs and symptoms.
  • Hypoglycaemia (insulin shock) is caused by insulin overdose, failure to eat or excessive or very high intensity exercise rapidly affecting the nervous system with, e.g., headache, difficulty in problem solving, disturbed or altered behaviour, slurred speech, staggering gait, coma and seizures. Increased autonomic nervous system symptoms include: hunger, anxiety, tachycardia, sweating and cool clammy skin.

• Chronic complications are associated with hyperglycaemia, accumulation of glycated end products and activation of metabolic pathways damaging the tissues. These are: microvascular (damage to capillaries) or macrovascular (damage to larger vessels).
  • Microvascular complications due to thickening of the basement membrane and cross-linking of molecules due to raised blood glucose levels which can block smaller blood vessels leading to hypoxia and tissue ischemia. The major organs and systems affected are: kidneys (nephropathy); eyes (retinopathy); nervous system (neuropathy) affecting central nervous system, sensorimotor nerves, autonomic nervous system. Most frequent is damage to the sensation and movement of the legs.
  • Macrovascular complications cause damage to medium and larger blood vessels and the organs supplied. Common conditions include: atherosclerotic changes causing coronary artery disease, stroke, peripheral vascular disease and damage to the feet which can result in diabetic foot ulcers and lower limb amputation.
  • Management is associated with controlling blood glucose levels by balancing the diet and insulin in the blood maintained by oral drug therapy or insulin administration.
  • Development of complications can be reduced with strict control of blood glucose levels.

Answer: Acute liver disorders occur rapidly without earlier indications. It can be due to: viral infection; drug-induced, e.g. paracetamol; toxin,: e.g death cap mushroom; acute fatty liver of pregnancy; vascular conditions plus other causes. In acute liver failure, the presentation includes: prolonged prothrombin time, decline in mental function, peripheral vasodilation, indications of systemic inflammatory response syndrome, and eventually multi-organ failure.

Chronic liver disease develops over time due to repeated damage to the cells of the liver due to similar causes as above and can lead to cirrhosis and hepatocellular cancer. Two other major categories are alcohol-related liver disease and non-alcoholic fatty liver disease (NAFLD).

Cirrhosis causes structural injury liver results from injury and fibrosis with inflammation leading to progressive loss of liver function damaging the liver structure and its blood supply. These changes impede blood flow causing portal hypertension leading to diversion of blood from the high-pressure hepatic portal vein causing decreased life expectancy and quality of life. Symptoms are: tenderness in right upper quadrant of the abdomen, ascites, peripheral oedema, jaundice, pruritus, anorexia, malnutrition and fatigue, bruising and bleeding tendencies. Management is primarily supportive, including the use of diuretics, vitamin K, blood products, antibiotics and appropriate nutritional care.

Complications of chronic liver disease are: portal hypertension, ascites. oesophageal varices. hepatic encephalopathy, disrupted protein metabolism, central nervous system (CNS) manifestations of liver failure, anaemia, bruising and bleeding.