Cardiovascular Disease, Diabetes
and Obesity
• (c) Pathology of cardio vascular disease (CVD).
• (i) Process of atherosclerosis, its effect on arteries and
blood pressure and its link to cardiovascular diseases
(CVD).
Atherosclerosis
Contributing factors to the
development of atherosclerosis
• High blood
pressure
• Carbon monoxide
in cigarettes
• Diabetes
• High blood
cholesterol levels
Hypertension (high blood pressure)
• Hypertension is a major risk
factor for many diseases
including coronary heart
disease.
Of hearts and hypertension film
• http://www.hhmi.org/biointeractive/hearts-and-hypertensionblazing-genetic-trails
Consequences
• Atherosclerosis is the root cause of various cardio vascular diseases
including
•
•
•
•
angina
heart attack
stroke
peripheral vascular disease
Atherosclerosis
• Atherosclerosis is the accumulation of fatty
material (consisting mainly of cholesterol),
fibrous material and calcium forming an
atheroma, also known as a 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.
• Examine league tables for coronary heart disease worldwide.
• Examine trends in coronary heart disease over last 10 years.
• (ii) Thrombosis— Events leading to a myocardial
infarction (MI) or stroke.
• Endothelium damage, clotting factors and the role of
prothrombin, thrombin, fibrinogen and fibrin.
Thrombus formation and effects of an embolus.
Thrombosis
THROMBOSIS
• A thrombus is a
blood clot that forms
inside a blood vessel
or cavity of the
heart.
• Thrombosis is the
formation or
presence of a blood
clot inside a blood
vessel or the heart.
Thrombosis
Clotting of Blood
• a) Damaged endothelial cells 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.
Thrombosis
• Atheromas may rupture damaging the
endothelium. The damage releases clotting
factors that activate 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.
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.
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.
Myocardial Infarction
(Heart Attack or Coronary Thrombosis)
Clot stops flow of
blood
Plaque build-up on vessel walls
Where the blockage occurs in the
artery
Where the heart is affected
Myocardial infraction
• 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. Either way, cells are deprived of
oxygen, leading to death of the tissues.
• Investigate the use of thrombolytic medications such as streptokinase
and tissue plasminogen activator.
• Compare and contrast the use of antiplatelet and anticoagulants
therapies.
• Investigate examples of bleeding disorders such as Von Willebrand
disease and haemophilia A, B and C.
• (iii) Causes of peripheral vascular disorders including
narrowing of arteries due to atherosclerosis, deep
vein thrombosis (DVT) and pulmonary embolism due
to blood clots.
Peripheral Vascular Disorders
Peripheral Vascular Disease
• Caused by
narrowing of the
arteries other
than those of the
heart or brain
• 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.
Peripheral vascular disease
• 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 Deep Vein Thrombosis (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 if it travels to a blood vessel
supplying the lungs.
• (iv) Control of cholesterol levels and familial
hypercholesterolaemia.
• Cholesterol synthesis and its function in the cell
membrane and in steroid synthesis.
• Roles of high density lipoproteins (HDL) and low
density lipoproteins (LDL). LDL receptors, negative
feedback control and atheroma formation. Ratios of
HDL to LDL in maintaining health, the benefits of
physical activity and a low fat diet. Reducing blood
cholesterol through prescribed medications.
Control of Cholesterol Levels
Cholesterol facts
• Found in the diet – eggs, dairy etc
• Made up of lipids, component of the cell membrane and required for
steroid synthesis
• Removed by the liver
• 2 types of cholesterol carrying proteins in the blood:
1. High density lipoproteins (HDL)
2. Low density lipoproteins (LDL)
HDL transports excess
cholesterol from the body
cells to the liver for
elimination.
This prevents
accumulation of
cholesterol in the blood.
A higher ratio of HDL to
LDL will result in lower
blood cholesterol and a
reduced chance of
atherosclerosis.
Cholesterol
• Most cholesterol is synthesised by the liver from
saturated fats in the diet. Cholesterol is a component of
cell membranes and needed for steroid synthesis. There
are two types of cholesterol carrying proteins:
1. High density lipoproteins (HDL)
2. Low density lipoproteins (LDL)
• HDL transport excess cholesterol from the body cells to
the liver for elimination. This prevents accumulation of
cholesterol in the blood. A higher ratio of HDL to LDL will
result in lower blood cholesterol and a reduced chance of
atherosclerosis.
• 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.
Cholesterol
• 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.
• Research data on the action of cholesterol reducing drugs.
• Investigate current views on the use of statins in treatment of
patients at risk of CVD.
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.
Reducing cholesterol
• Regular exercise tends to raise HDL levels, removing more
cholesterol from the blood.
• 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.
• Genetic screening of familial hypercholesterolaemia
(FH) and its treatments.
Familial Hypercholesterolaemia
Familial Hypercholesterolaemia
Families,
inherited
High levels
cholesterol
a condition
• Familial hypercholesterolaemia (FH) is due to
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 (see reducing
cholesterol) and drugs.
• Cell receptors and the role of hormones in negative feedback control
of blood glucose through insulin, glucagon and adrenaline
(epinephrine).
Regulation of Blood Glucose Levels
Blood Glucose Regulation
‘Fight or Flight’ situation.
• The adrenal glands
secrete the hormone
adrenaline
(epinephrine).
• Promotes glycogen
breakdown in liver
• Inhibits insulin secretion
Blood glucose regulation
• Receptors in the pancreas respond to high blood glucose levels by
producing insulin which activates the conversion of glucose to glycogen
in the liver and so decreases blood glucose concentration.
• Receptors also respond to low blood glucose levels by producing
glucagon which activates the conversion of glycogen to glucose in the
liver and so increases blood glucose level.
• During exercise and ‘fight or flight’ responses, glucose levels are
raised by adrenaline (epinephrine) released from the adrenal glands
which stimulate glucagon secretion and inhibit insulin secretion.
•
• Regulating blood glucose levels animation:
• http://www.abpischools.org.uk/page/modules/diabetes_16plus/diab
etes3.cfm?coSiteNavigation_allTopic=1
Diagnosing 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.
Glucose Tolerance Test
Hormone effects on organs animation
• http://www.abpischools.org.uk/page/modules/diabetes_16plus/diab
etes3.cfm?coSiteNavigation_allTopic=1
• Drag and drop quiz at bottom
Diabetes
The glucose tolerance test measures how quickly blood
glucose levels return to normal after fasting then and two
hours after drinking 250-300ml of glucose solution.
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.
• Diagnosis, treatments and role of insulin in type 1 and type 2
diabetes.
Type 1 and Type 2 Diabetes
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
Diabetes UK
• Diabetes film
• http://www.diabetes.org.uk/Guide-to-diabetes/What-is-diabetes/
Type 1 diabetes
• NHS film
• http://www.nhs.uk/Conditions/Diabetestype1/Pages/Introduction.aspx
• Chandler’s story
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
Type 2 diabetes
• Risk calculator:
• www.nhs.uk/Conditions/Diabetes-type2/Pages/Introduction.aspx
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.
Type 1 and 2
diabetes
Read diabetes articles
Gene therapy to diabetic treatment
• 2 short videos:
• http://www.abpischools.org.uk/page/modules/diabetes_16plus/diab
etes9.cfm?coSiteNavigation_allTopic=1
Diabetes
• Type 1 diabetes usually occurs in childhood. Type 1 diabetics are
unable to produce insulin and can be treated with regular doses of
insulin injections.
• Type 2 diabetes or adult onset diabetes typically 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
leading to a failure to convert glucose to glycogen. Treatment involves
a low sugar diet, regular exercise and decreasing calories within the
diet to reduce any obesity.
• (v) Blood glucose levels
• Chronic elevated blood glucose levels leads to
atherosclerosis and blood vessel damage.
Blood Glucose levels, Atherosclerosis and
Blood Vessel Damage
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.
• 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
BLEEDING (THE RED BLOTS) FROM
BLOOD
VESSEL WALLSvascular
DUE TO
• Can leadWEAK
to
peripheral
disease,
DIABETES
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
• Investigate the symptoms associated with ‘microvascular disease’ and
‘macrovascular’.
Diabetic ulceration
Blood glucose levels
Chronic (long term) elevation of blood glucose levels
leads to the endothelium cells taking in more glucose
than normal which damages 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.
Diabetes
ABPI schools
• Hormones drag and drop exercise:
• http://www.abpischools.org.uk/page/modules/hormones/horm10.cf
m?coSiteNavigation_allTopic=1
ABPI schools
• Diabetes quiz questions:
• http://www.abpischools.org.uk/page/modules/diabetes_16plus/diab
etes2.cfm?coSiteNavigation_allTopic=1
• And
http://www.abpischools.org.uk/page/modules/diabetes_16plus/diab
etes10.cfm?coSiteNavigation_allTopic=1
• (vi) Obesity linked to cardiovascular disease and diabetes.
• Definition and characterisation of obesity. Body fat, body density
measurements and BMI calculations. Role of exercise in reducing
CVD.
• Compare measurement of body composition using different methods. For
example using densitometry, skin fold thicknesses, bioelectrical impedance,
waist-hip ratio and body mass index.
• Perform simple measurements of body composition.
• Analyse data which illustrates the effect of exercise on body composition.
• Examine case histories using coronary heart disease risk calculators (eg
Framingham index).
• Examine risk factors and remedial measures in treating cardiovascular disease.
Obesity -Cardiovascular Disease and
Diabetes
Obesity-Risk Factor
• Obesity is a major risk factor for
cardiovascular disease and type
2 diabetes
Obesity
• Body mass index (BMI) is a simple index
commonly used to classify overweight and
obesity in adults.
• Body mass index greater than 30 is used to
indicate obesity.
Body Mass Index (BMI)
Classification
BMI (kg/m2)
Associated health
risks
Underweight
Less than 18.5
Low
Normal
18.5 - 24.9
Average
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.
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
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)
• Percentage body fat can then be calculated
Obesity
• Obesity is a major risk factor for cardiovascular
disease and type 2 diabetes. Obesity is characterised
by excess body fat in relation to muscle tissue.
• A body mass index (BMI) is used to estimate levels of
obesity.
BMI =
• A BMI over 30 is used to indicate obesity. Accurate
measurement of body fat requires the measurement
of body density.
• Skin fold thickness measurements can indicate skin
fat levels by using callipers.
Treatment of Obesity
• Limit fats and free sugars in diet
• 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 and sugars
naturally present in honey, syrups, fruit juices and
fruit concentrates
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
Obesity
• Obesity is linked to high fat diets and a decrease in
physical activity. The energy intake in the diet should
limit fats as fats have a high number of calories per
gram. Energy intake should also limit free sugars as
they require no metabolic energy to be expended in
their digestion.
• Exercise increases energy expenditure and preserves
lean tissue. It can help to reduce risk factors for CVD
by keeping weight under control, minimising stress,
reducing hypertension (high blood pressure) and
improving HDL levels in the blood.