1. Cardiovascular Disease, Diabetes and Obesity

2. What You Should Know Atherosclerosis is the accumulation of fatty material (consisting mainly of cholesterol), fibrous material and calcium forming an atheroma or plaque beneath the endothelium. As the atheroma grows the artery thickens and loses its elasticity. The diameter of the artery becomes reduced and blood flow becomes restricted resulting in increased blood pressure. Atherosclerosis is the root cause of various cardio vascular diseases including angina, heart attack, stroke and peripheral vascular disease.

3. Atherosclerosis Atherosclerosis is the accumulation of a lipid containing material known as atheroma or plaque beneath the inner lining of the arteries Plaque is made up of fat, cholesterol, calcium and other substances found in your blood (Atheroma is the ancient Greek word for porridge, the deposits look like blobs of porridge.) It causes a narrowing of the diameter of the arteries restricting blood flow Reduction of diameter is often accompanied by loss of elasticity of the artery walls (hardening) causing an increase in blood pressure

6. Contributing factors to the development of atherosclerosis High blood pressure Carbon monoxide in cigarettes Diabetes High blood cholesterol levels

7. Consequences Atherosclerosis is the root cause of various cardio vascular diseases including –angina –heart attack –stroke –peripheral vascular disease

8. Thrombosis

9. What You Should Know Atheromas may rupture damaging the endothelium. The damage releases clotting factors that activate a cascade of reactions resulting in the conversion of the enzyme prothrombin to its active form thrombin. Thrombin then causes molecules of the plasma protein fibrinogen to form threads of fibrin. The fibrin threads form a meshwork that clots the blood, seals the wound and provides a scaffold for the formation of scar tissue. The formation of a clot (thrombus) is referred to as thrombosis. In some cases a thrombus may break loose forming an embolus and travel through the bloodstream until it blocks a blood vessel. A thrombosis in a coronary artery may lead to a heart attack (MI). A thrombosis in an artery in the brain may lead to a stroke. Cells are deprived of oxygen leading to death of the tissues

10. THROMBOSIS thrombusA thrombus is a blood clot that forms inside a blood vessel or cavity of the heart. ThrombosisThrombosis is the formation or presence of a blood clot inside a blood vessel or cavity of the heart.

11. Thrombosis

12. Clotting of Blood Clotting is the mechanism that prevents blood loss from broken blood vessels. a) Platelets or damaged cells release a group of proteins called clotting factors. These clotting factors are released into the plasma at a wound site. b) Clotting factors activate the enzyme Thrombin from its inactive form to prothrombin c) Thrombin turns the soluble plasma protein fibrinogen into its insoluble fibrous form Fibrin. d) The fibrin threads form a meshwork that clots the blood by binding platelets and blood cells to form a ‘plug’ (clot) to seal the wound and provide a scaffold for the formation of scar tissue

13. Thrombosis The plaque from atherosclerosis provides a roughened surface that allows blood platelets to accumulate. The platelets release clotting factors, which may result in the formation of a blood clot or thrombus at the site of plaque formation. If the thrombus grows large enough to obstruct the artery completely, a thrombosis occurs. For example, a coronary thrombosis closes off a blood vessel in the heart.

14. If the thrombus breaks loose from the site of formation (embolus), it travels along the blood stream until it reaches an artery too narrow to allow it to get through.

15. Stroke A stroke means that the blood supply to a part of the brain is suddenly cut off. The brain cells need a constant supply of oxygen from the blood. Soon after the blood supply is cut off, the cells in the affected area of the brain become damaged or die.

16. Myocardial Infarction (Heart Attack or Coronary Thrombosis) Plaque build-up on vessel walls Clot stops flow of blood Where the heart is affected Where the blockage occurs in the artery Heart attack or ‘coronary’ are common terms for the disorder myocardial infarction, which means, literally, death of part of the heart muscle following a blockage in its blood supply

17. Myocardial infraction

18. Peripheral Vascular Disorders

19. What You Should Know Peripheral vascular disease is narrowing of the arteries due to atherosclerosis of arteries other than those of the heart or brain. The arteries to the legs are most commonly affected. Pain is experienced in the leg muscles due to a limited supply of oxygen. A DVT is a blood clot that forms in a deep vein most commonly in the leg, and can break off and result in a pulmonary embolism.

20. Peripheral Vascular Disease Caused by narrowing of the arteries other than those of the heart or brain you may not know that you have the condition. If you do get symptoms, the most common is pain or cramp in your calf (lower leg) or less commonly in your thigh, buttock muscles or feet. The pain will come on after walking or doing other exercise as oxygen supply to the cells will be restricted. It will usually go away within a few minutes of you stopping the exercise.

21. Deep Vein Thrombosis A DVT is a blood clot that forms in a deep vein most commonly in the leg, and can break off and result in a pulmonary embolism

22. Control of Cholesterol Levels and Familial Hypercholesterolaemia.

23. What You Should Know Most cholesterol is synthesised by the liver from saturated fats in the diet. Cholesterol is a component of cell membranes and a precursor for steroid synthesis. HDL transports excess cholesterol from the body cells to the liver for elimination. This prevents accumulation of cholesterol in the blood. LDL transports cholesterol to body cells. Most cells have LDL receptors that take LDL into the cell where it releases cholesterol. Once a cell has sufficient cholesterol a negative feedback system inhibits the synthesis of new LDL receptors and LDL circulates in the blood where it may deposit cholesterol in the arteries forming atheromas. A higher ratio of HDL to LDL will result in lower blood cholesterol and a reduced chance of atherosclerosis. Regular physical activity tends to raise HDL levels, dietary changes aim to reduce the levels of total fat in the diet and to replace saturated with unsaturated fats. Drugs such as statins reduce blood cholesterol by inhibiting the synthesis of cholesterol by liver cells.

24. Cholesterol Lipid Component of cell membrane Found in the diet – Eggs, dairy, liver High levels lead to development of CHD 2 types of cholesterol -carrying proteins (HDL, LDL) Low-density Lipoproteins (LDL) - bad cholesterol High-density Lipoproteins (HDL) - good cholesterol LDL- carries up to 70% Blood cholesterol from liver to body cells As level of LDL increases, Level of CHD increases HDL- carries 20% Blood cholesterol HDL- gathers Cholesterol from body cells for elimination by liver As level of HDL Increases, risk of CHD decreases

25. Once a cell has sufficient cholesterol a negative feedback system inhibits the synthesis of new LDL receptors and LDL circulates in the blood where it may deposit cholesterol in the arteries forming atheromas. A higher ratio of HDL to LDL will result in lower blood cholesterol and a reduced chance of atherosclerosis. Receptor mediated endocytosis

26. Lowering Cholesterol Levels Regular physical activity tends to raise HDL levels Dietary changes aim to reduce the levels of total fat in the diet and to replace saturated with unsaturated fats. Drugs such as statins reduce blood cholesterol by inhibiting the synthesis of cholesterol by liver cells.

27. Familial Hypercholesterolaemia

28. What You Should Know Familial hypercholesterolaemia (FH) is caused by an autosomal dominant gene, which predisposes individuals to developing high levels of cholesterol. FH genes cause a reduction in the number of LDL receptors or an altered receptor structure. Genetic testing can determine if the FH gene has been inherited and it can be treated with lifestyle modification and drugs

29. Familial Hypercholesterolaemia Familial hypercholesterolaemia is an inherited condition The level of low-density lipoprotein (LDL) cholesterol in the blood is higher than normal from birth It is caused by a defect in a gene which controls the way cholesterol is handled in the body As a result of the defect, LDL receptor number is reduced or the structure altered. This stops the LDL from unloading its cholesterol into the cell. LDL cholesterol is not broken down properly and builds up in the bloodstream. In most cases the defective gene is inherited from one parent (heterozygous inheritance, autosomal) Results in the development of heart disease at a young age. This is caused by plaques of atheroma developing within the walls of the coronary (heart) arteries

31. Treatment Eating healthily Getting a reasonable amount of exercise. Avoiding smoking. Maintaining a normal weight. Use of statins

32. Blood Glucose levels, Atherosclerosis and Blood Vessel Damage

33. What You Should Know Chronic elevation of blood glucose levels leads to the endothelium cells taking in more glucose than normal damaging the blood vessels. Atherosclerosis may develop leading to cardio vascular disease, stroke or peripheral vascular disease. Small blood vessels damaged by elevated glucose levels may result in haemorrhage of blood vessels in the retina, renal failure or peripheral nerve dysfunction.

34. Blood Glucose Levels and Vascular Disease Normal blood glucose levels 5 mmol/l If a person has untreated diabetes blood glucose levels become elevated Chronic level of 30mmol/l

35. Elevated blood glucose levels cause the endothelial cells lining the blood vessels to absorb more glucose than normal This cause damage to the blood vessels Can lead to peripheral vascular disease, CVD or stroke Small blood vessels damaged by elevated glucose levels may result in haemorrhage of blood vessels in the retina, renal failure or peripheral nerve dysfunction BLEEDING (THE RED BLOTS) FROM WEAK BLOOD VESSEL WALLS DUE TO DIABETES

36. Regulation of Blood Glucose Levels

37. What You Should Know Pancreatic receptors respond to high blood glucose levels by causing secretion of insulin. Insulin activates the conversion of glucose to glycogen in the liver decreasing blood glucose concentration. Pancreatic receptors respond to low blood glucose levels by producing glucagon. Glucagon activates the conversion of glycogen to glucose in the liver increasing blood glucose level. During exercise and fight or flight responses glucose levels are raised by adrenaline (epinephrine) released from the adrenal glands. Epinephrine stimulates glucagon secretion and inhibits insulin secretion

38. Blood Glucose Regulation

39. Control of Blood Sugar Level This is by homeostatic control. Cells in the pancreas (islets of Langerhans) monitor blood glucose levels The pancreas secretes 2 hormones which work antagonistically to return glucose levels in the blood to normal Hormones are insulin and glucagon

40. Increase in Blood Glucose When glucose levels in the blood increase Pancreas secretes more This insulin increases permeability of cells to glucose They take in more glucose for fuel The insulin also travels to the liver where high insulin levels also make the liver cells more permeable to glucose so they absorb more In the liver cells the glucose molecules are joined to form glycogen which is stored in the liver. Glucose levels in the blood return to normal

41. Decrease in Blood Glucose Glucagon released by the pancreas stimulates the conversion of glycogen to glucose Glucose levels in the blood return to normal

43. Adrenaline (epinephrine) In an emergency - ‘Fight or Flight’ - situation. when the body needs additional glucose supplies, adrenaline is released from the adrenal glands Epinephrine overrides the homeostatic control and promotes the breakdown of glycogen by glucagon to glucose. Epinephrine inhibits insulin secretion

44. Adrenal Glands The adrenal glands are located above the kidneys and they secrete the hormone adrenaline (epinephrine).

45. Type 1 and Type 2 Diabetes

46. What You Should Know Vascular disease can be a chronic complication of diabetes. Type 1 diabetes usually occurs in childhood. Type 2 diabetes or adult onset diabetes typically develops later in life and occurs mainly in overweight individuals. A person with type 1 diabetes is unable to produce insulin and can be treated with regular doses of insulin. In type 2 diabetes individuals produce insulin but their cells are less sensitive to it. This insulin resistance is linked to a decrease in the number of insulin receptors in the liver leading to a failure to convert glucose to glycogen.

47. What is Diabetes Mellitus? A failure to control blood glucose levels and an impaired ability to store glucose in the form of liver and muscle glycogen

48. Type 1 Diabetes Type 1- usually occurs in childhood. A person with type 1 diabetes is unable to produce insulin and can be treated with regular doses of insulin

49. Type 2 Diabetes Type 2 diabetes or adult onset diabetes develops later in life and occurs mainly in overweight individuals. Type 2 diabetics produce insulin but their cells are less sensitive to it. This insulin resistance is linked to a decrease in the number of insulin receptors in the liver This leads to a failure to convert glucose to glycogen.

50. Symptoms of Diabetes Mellitus Classic symptoms of diabetes are – Frequent urination, with large volumes of urine (especially at night) Excessive thirst Hunger Weight loss Other symptoms – Fatigue Blurry vision Gum and urinary tract infections Slow healing of skin

51. Complications Associated with Diabetes Nerve damage Vascular disease can be caused by chronic diabetes –Hypertension –Stroke –Kidney disease –Increased risk of atherosclerosis –Impaired vision due to cataracts or damaged retinas.

53. Diabetic ulceration

55. Diagnosis of Diabetes

56. What You Should Know In both types of diabetes individual blood glucose levels will rise rapidly after a meal. The kidneys are unable to cope resulting in glucose being lost in the urine. Testing urine for glucose is often used as an indicator of diabetes. The glucose tolerance test is used to diagnose diabetes. The blood glucose levels of the individual are measured after fasting and two hours after drinking 250–300 ml of glucose solution.

57. Testing for Diabetes In both types of diabetes blood glucose levels rise sharply after a meal The kidneys are unable to cope with the high glucose levels and therefore glucose is lost in the urine A urine test for glucose is often used as an indicator of diabetes

58. Glucose Tolerance Test If your urine tests positive for glucose then a glucose tolerance test is used to diagnose diabetes Prior to having the test, you will be asked not to eat or drink certain fluids for 8-12 hours. Before the test, a blood sample is taken so your blood glucose can be measured. You will then be given a sweet glucose drink. After drinking the glucose drink, your blood glucose will be measured again after two hours.

59. Glucose Tolerance Curve

60. Obesity -Cardiovascular Disease and Diabetes

61. What You Should Know Obesity is a major risk factor for cardiovascular disease and type 2 diabetes. Obesity is characterised by excess body fat in relation to lean body tissue (muscle). A body mass index (weight divided by height squared) greater than 30 is used to indicate obesity. Accurate measurement of body fat requires the measurement of body density. Obesity is linked to high fat diets and a decrease in physical activity. The energy intake in the diet should limit fats and free sugars as fats have a high calorific value per gram and free sugars require no metabolic energy to be expended in their digestion. Exercise increases energy expenditure and preserves lean tissue. Exercise can help to reduce risk factors for CVD by keeping weight under control, minimising stress, reducing hypertension and improving HDL blood lipid profiles.

62. Obesity-Risk Factor Obesity is a major risk factor for cardiovascular disease and type 2 diabetes

63. Obesity Obesity is characterised by excess body fat in relation to lean body tissue (muscle). Body mass index (BMI) is a simple index of weight-for-height that is commonly used to classify overweight and obesity in adults. It is defined as a person's weight in kilograms divided by the square of his height in meters A body mass index greater than 30 is used to indicate obesity.

64. Body Mass Index (BMI) ClassificationBMI (kg/m2)Associated health risks UnderweightLess than 18.5Low Normal18.5 - 24.9Average Overweight Moderate Obese class 1 Obese class 2 Obese class 3 Greater than 25.0 25.0 – 29.9 30.0 – 34.9 35.0 – 39.9 Greater than 40.0 Increased Moderate increase. Severe increase. Very severe increase.

65. Disadvantage of Calculating BMI Classification by BMI may result in an individual being classified as overweight or obese, when in fact they have a relatively low percentage body fat but a large bone mass or muscle bulk. Eg. – body builders

66. Densitometry An accurate measurement of body fat requires the measurement of body density Densitometry depends on the fact that fat is less dense than lean tissue Measurement of body density by underwater weighing Density= body mass(g) body volume(cm³)(vol of water displaced) Percentage body fat can then be calculated

67. Causes of Obesity High fat diet Energy intake should limit fats and free sugars Fats have a high calorific value Free sugars need no metabolic energy to be expended to digest them. Free sugars include monosaccharides and disaccharides that are added to foods by manufacturers, cooks or consumers, and sugars naturally present in honey, syrups, fruit juices and fruit concentrates Decrease in physical activity

68. Why Exercise? Exercise increases energy expenditure It preserve lean tissue Exercise can help to reduce the risk factors for CVD by –keeping weight under control –Minimising stress –Reducing hypertension –Improving HDL blood lipid profiles