1

Causes of death
Leading causes of death, Australia, 2014
Cause of death Rank Number
Ischaemic heart diseases 1 20 173
Dementia and Alzheimer disease 2 11 965
Cerebrovascular diseases 3 10 765
Trachea, bronchus, lung cancer 4 8 251
Chronic lower respiratory diseases 5 7 810
Diabetes 6 4 348
Blood and lymph cancer (including leukaemia) 7 4 275
Colon, sigmoid, rectum and anus cancer 8 4 169
Heart failure 9 3 447
Urinary system 10 3 136

Data from Australian Bureau of Statistics, 3303.0 Causes of Death Australia 2013, Mar 2016 2
Cause of death Rank Number Males
Ischaemic heart diseases 1 11 082
Trachea, bronchus, lung cancer 2 4 947
Cerebrovascular diseases 3 4 279
Chronic lower respiratory diseases 4 4 164
Dementia, including Alzheimer disease 5 4 106
Prostate cancer 6 3 102
Blood and lymph cancer (including leukaemia) 7 2 413
Colon, sigmoid, rectum and anus cancer 8 2 279
Diabetes 9 2 213
Intentional self harm 10 2 157 Females
Cause of death Rank Number
Ischaemic heart diseases 1 9 091
Dementia and Alzheimer disease 2 7 859
Cerebrovascular diseases 3 6 486
Chronic lower respiratory diseases 4 3 646
Trachea, bronchus, lung cancer 5 3 304
Breast cancer 6 2 814
Diabetes 7 2 135
Heart failure 8 1 975
Colon, sigmoid, rectum and anus cancer 9 1 890
Data from Australian Bureau of Statistics, 3303.0
Causes of Death Australia 2013, Mar 2016 Blood and lymph cancer (including leukaemia) 10 1 3862
http://www.abs.gov.au/ausstats/abs@.nsf/Lookup/by%20Subject/3303.0~2014~Main%20Features~
4
Summary%20of%20Findings~1, Last accessed July 2016
5
 Systemic and pulmonary circuits
Systemic circuit
Blood supply to and
from all body tissues
Pulmonary circuit
Blood supply to and
from lungs (for
oxygenation)

6
Craft & Gordon, Understanding Pathophysiology 2nd ed 2015, Fig 22-1
 Pathway of blood through the circulation

7
Craft & Gordon, Understanding Pathophysiology 2nd ed 2015, Fig 22-2
 Structure of capillaries

Booth & Wyman, Anatomy, physiology, and pathophysiology for allied health. 2nd edn, 2009, Fig 5-9 and 5-10. 8
 Anatomy of the heart

9
Craft & Gordon, Understanding Pathophysiology 2nd ed 2015, Fig 22-16C
 Coronary arteries
Branch off the aorta
Lead into capillaries
supply cardiac tissue

Left main coronary artery

Right coronary artery

10
Craft & Gordon, Understanding Pathophysiology 2nd ed 2015, Fig 22-16A
 Coronary veins
Drain into coronary sinus (posterior surface of
heart)
Empties into right atrium

11
Craft & Gordon, Understanding Pathophysiology 2nd ed 2015, Fig 22-16 B
 Cardiac conduction system
Sequence of excitation
Sinoatrial node: pacemaker, 100
impulses per minute
Atrioventricular node
Atrioventricular bundle (Bundle of His)
Right and left bundle branches
Purkinje fibres

Parasympathetic nervous system slows

heart rate
Sympathetic nervous system increases
heart rate

12
Telser, Elseviers integrated histology, 2007, Fig 7-2
 Electrocardiogram (ECG)

13
Craft & Gordon, Understanding Pathophysiology 2nd ed 2015, Fig 22-25
 ECG and cardiac mechanical events

14
Fox, Human Physiology, 8th edn, 2004, Fig 13.21
 ECG and cardiac mechanical events
ECG deflection Electrical Mechanical event
event
P wave Atrial depolarisation Atrial contraction

QRS complex Ventricular Ventricular

depolarisation contraction
T wave Ventricular Ventricular
repolarisation relaxation
Systole: contraction
Diastole: relaxation 15
16
 Cardiac innervation
Cardiac control centres in
brainstem
Cardioinhibitory centre
decreases heart rate
Via parasympathetic
nervous system
Cardioexcitatory centre
increases heart rate
Via sympathetic nervous
system, 1-receptors in heart
17
Marieb & Hoehn, Human Anatomy and Physiology, 7th edn, 2007, Fig 18-15
 18
Craft & Gordon, Understanding Pathophysiology 2nd ed 2015, Fig 22-16 B
 Sympathetic neurotransmitters
Adrenaline and noradrenaline
Released from sympathetic nervous system as
neurotransmitters
Released from adrenal medulla as hormones
Occurs when the sympathetic nervous system
signals the adrenal medulla

Adrenaline and noradrenaline are similar

Usually have the same effect
Both bind to adrenergic receptors

19
 Adrenergic receptors
Receptor type Location Effect of adrenaline or
noradrenaline binding
Alpha ()1 Arteries supplying Vasoconstriction
receptors skin and visceral
organs
Beta ()1 receptors Heart (muscle) Increases heart rate;
increases force of
contraction
Beta ()2 receptors Coronary arteries Vasodilation

Beta ()2 receptors Respiratory Bronchodilation

bronchioles
20
21
 Blood pressure in vessels of the
systemic circulation

22
Craft & Gordon, Understanding Pathophysiology 2nd ed 2015, Fig 22-38
 Peripheral resistance
Opposition to blood flow due to friction
Depends on:
Diameter of blood vessel
Adjusted constantly
Vasoconstriction increases resistance and BP

Blood viscosity
Thicker blood increases BP

23
 Control of arterial blood pressure

Determined by:
cardiac output
peripheral resistance,
by altering blood
vessel diameter Vasoconstriction: Vasodilation:
decreases diameter increases diameter
increases resistance decreases resistance
increases BP decreases BP

BP = CO x PR
Blood pressure = cardiac output x peripheral resistance
24
https://www.physicool.co.uk/wp-content/uploads/2014/04/vasoconstriction.jpeg, Last accessed Feb 2016
 Oxygen and cardiac muscle
Cardiac muscle uses 75% of oxygen in coronary
circulation at rest
Compared with overall body usage of 25% of
oxygen

Cardiac muscle unable to extract much more

oxygen in times of increased oxygen demand eg
during exercise
Increase cardiac muscle oxygenation by coronary
vasodilation

25
Short-term control of blood pressure:
Nervous system (1)
Chemoreceptor reflex
Chemoreceptors (in aortic arch and carotid sinus)
Detect low pH, low O2
Stimulates cardioexcitatory centre to increase HR, and
vasoconstriction

26
Short-term control of blood pressure:
Nervous system (2)
Baroreceptor reflex
Baroreceptors (in carotid arteries and aortic arch)
Detect changes in stretch eg when stretched less (due to
decreased blood pressure)
Stimulates cardioacceleratory centre to increase HR, and
vasoconstriction

27
 Baroreceptor reflex for
low blood pressure

28
Marieb & Hoehn, Human Anatomy and Physiology, 8th edn, Fig 19.9
 Baroreceptor reflex for
high blood pressure

29
Marieb & Hoehn, Human Anatomy and Physiology, 8th edn, Fig 19.9
 Long-term control of blood pressure:
Renin-angiotensin-aldosterone
Decreased blood pressure detected by kidney
Kidney releases renin: converts angiotensinogen to
angiotensin l
Angiotensin converting enzyme (ACE): converts
angiotensin I to angiotensin II (mainly in lungs)
Angiotensin II: causes aldosterone secretion from
adrenal gland, resulting in:
Reabsorption of sodium and water by kidney
Increased blood volume
Increased blood pressure
30
 Renin-Angiotensin-Aldosterone system
Decrease in BP Kidneys reabsorb
detected by kidneys Na and water

31
Craft & Gordon, Understanding Pathophysiology 2nd ed 2015, Fig 28-15
32
 Medications for Cardiovascular system (1)
Type Generic name Action
Anticoagulants eg Heparin, Inhibits coagulation (prevent fibrin mesh)
Warfarin Inhibits thrombus formation
Antiplatelets eg Aspirin, Inhibit platelet aggregation
Cartia Inhibits thrombus formation
Angiotensin- eg Captopril, Inhibits conversion of angiotensin I to angiotensin II,
converting Enalapril so less aldosterone
enzyme (ACE) Decrease blood pressure
inhibitors
Angiotensin II eg Irbesartan, Blocks angiotensin II receptors, so less aldosterone
blockers (ARBs) Losartan Decrease blood pressure

Beta blockers Selective 1- Blocks effects of adrenaline / noradrenaline at

(-blockers) blockers eg -receptors
Metoprolol, Decreases cardiac contractility and heart rate
Atenolol
33
Angiotensinogen
Renin

Angiotensin I
ACE (angiotensin converting enzyme)
ACE Inhibitors

Angiotensin II
Angiotensin receptors (adrenal cortex)
Angiotensin II receptor blockers

Aldosterone 34
Medications for Cardiovascular system (2)
Type Generic name Action
Calcium eg Diltiazem, Block calcium influx into cytoplasm
channel Verapamil Coronary artery vasodilation, improving perfusion
blockers Decreases contractility, lowers blood pressure
Coronary eg glyceryl Reduces myocardial demand for oxygen
vasodilators / trinitrate (GTN), Widespread vasodilation
nitrates nitroglycerine Coronary artery vasodilation, decreases
afterload
Digoxin Digoxin Increases intracellular calcium levels
Increases contractility
Diuretics eg Frusemide, Increase renal excretion of sodium and water
Spironolactone Decreases blood pressure
Lipid lowering eg Simvastatin, Liver draws LDL from the peripheral blood vessels
drugs Atorvastatin Decreases plasma lipid levels
Thrombolytics eg Breaks down fibrin mesh
Streptokinase Breaks down existing thrombus
35
36
 Dietary fats
Triglycerides
Monounsaturated fats (eg olive oil)
Polyunsaturated fats (eg fish)
Trans-unsaturated fats (eg processing of
polyunsaturated fats, deep fried foods)
Saturated fats (eg animal fats)
Phospholipids (eg plant and animal)
Cholesterol (eg animal fats, eggs)

37
 Sources of cholesterol
1. Dietary cholesterol (as per previous slide)

2. Produced by liver
Cells require cholesterol for cell membrane
Liver produces more cholesterol when the diet is
high in saturated and trans fats, and high blood
glucose level

Liver can also remove cholesterol from the

circulation

38
 Production of cholesterol
Cholesterol is produced by
the liver

Lipid-lowering drugs - statins

Modified from Nelms et al, Nutrition Therapy and Pahophysiology, 2nd ed, Fig 13-10 39
 Cholesterol in bile
Liver removes cholesterol
from the circulation through
the bile salts
Digestive function in emulsifying
fats in the small intestine
Bile salts are recycled via the
enterohepatic circulation

40
Sherwood, Human Physiology, 2004, Fig 16-17
 Cholesterol in hormones
Cholesterol is necessary for the production of
various hormones, including
Cortisol
Aldosterone
Testosterone
Oestrogen

41
Berg et al, Biochemistry 7th edn, Fig 26-27
 Transport of dietary fats
Lipoproteins: transport lipids in the blood
Lipids are insoluble in plasma (water-based)

Liver forms lipoproteins, including:

LDL: low density lipoprotein
HDL: high density lipoprotein

42
 LDL = low density
Lipoproteins: LDL lipoprotein,
bad cholesterol

Transports cholesterol to body tissues from liver

LDL deposits cholesterol at endothelial cells

(blood vessel lining)
Endothelial cells cannot break down
cholesterol
Excess cholesterol may accumulate

43
 HDL : high density
Lipoproteins: HDL lipoprotein,
good cholesterol

Transports cholesterol from body tissues to the liver

Liver can remove cholesterol from the circulation

Maintains endothelial cells

Inhibits movement of macrophages into the artery
wall
Prevents and removes lipids from artery wall

44
 Summary of LDL and HDL activity

45
Gould, Pathophysiology for Health Professionals, 3rd edn, Fig 18-11b
 Dyslipidaemia
Abnormal levels of lipids in the blood
Major risk factor for atherosclerosis

Dyslipidaemia includes:
Increased triglycerides
Increased LDL
Decreased HDL

May have xanthelasmas

46
Craft & Gordon, Understanding Pathophysiology 2nd ed 2015, Fig 23-15
 Risk factors
Modifiable:
High intake saturated and trans fatty acids
Stimulates liver production of cholesterol
High total energy intake, high intake cholesterol
Low intake mono- and poly- unsaturated fatty acids
These enhance excretion of cholesterol
Low intake of dietary fibre including wholegrain
cereals
Sedentary lifestyle
Smoking
Stress
Non-modifiable: familial hyperlipidaemia (genetic) 47
 Recommended target levels for
lipids in the blood

Lipids (mmol/L)
LDL < 2.0
HDL > 1.0
Triglycerides <2.0
Total cholesterol <4.0

Adapted from Craft & Gordon, Understanding Pathophysiology 2nd ed 2015, Table 23.4 48
 Prevention and Management
Dietary
Modifying amount and type of fat intake
Decreasing total energy intake
Increasing dietary fibre
Decreasing intake of simple carbohydrates
Exercise
Lipid-lowering drugs

49
50
 Atherosclerosis
Atherosclerosis: fatty deposits and hardening of artery
wall

Progressive accumulation of
lipids
inflammatory cells
smooth muscle cells
connective tissue

Becomes clinically important when vessel lumen

becomes occluded by 70% or more
51
https://myhealth.alberta.ca/health/pages/conditions.aspx?hwid=hw139808, Last accessed Feb 2016
 Atherosclerosis

52
http://media-2.web.britannica.com/eb-media/83/98483-004-FD45DAA5.jpg, Last accessed Feb 2016
 53
Craft & Gordon, Understanding Pathophysiology 2nd ed 2015, Fig 23-12A
 Risk factors for atherosclerosis
Modifiable risks Non-modifiable risks
Dyslipidaemia Increasing age
Male gender;
Hypertension
female after menopause
Obesity, sedentary lifestyle Family history of heart disease
Diabetes mellitus, insulin
Familial hyperlipidaemia (genetic)
resistance
Cigarette smoking Aboriginal and Torres Strait Islander
Inflammation
Stress 54
 Dyslipidaemia
Abnormal amounts of lipids in the blood
High total cholesterol, high LDL, or low HDL

55
 Hypertension
Consistent elevation of systemic arterial blood
pressure
Causes endothelial cell injury

56
 Obesity, sedentary lifestyle
Obesity: contributes to dyslipidaemia and
altered fat metabolism
Abdominal fat decreases HDL and increases BP

Sedentary lifestyle: decreases HDL and

increases LDL
Exercise increases HDL and decreases LDL

57
 Diabetes mellitus
Diabetes mellitus and insulin resistance:
characterised by hyperglycaemia
Cholesterol production is high during
hyperglycaemia
Hyperglycaemia: high blood glucose level

Hyperglycaemia causes:
Endothelial cell injury
Inflammation

58
 Smoking
Nicotine stimulates release of adrenaline and
noradrenaline
Increases HR, vasoconstriction, and BP

Endothelial cell injury

Increases LDL and decreases HDL

59
 Inflammation
Chronic inflammation contributes to heart
disease

C-reactive protein (CRP) in blood

Predicts cardiovascular risk and recurrent events in
patients who have coronary heart disease

60
 Stress
Increases production of cortisol
Cortisol promotes dyslipidaemia and increases blood pressure

Increases aldosterone and causes vasoconstriction

decreases renal perfusion
activates the renin-angiotensin-
aldosterone system (RAAS)
further increases blood pressure

61
Fox, Human Physiology, 2010, 11th ed, Fig 13-32
Aboriginal and Torres Strait Islander
Higher prevalence of risk factors for heart disease

May have more rapid disease progression

Exceedingly high age-standardised mortality

Risk calculated from age 45 for non-Indigenous

Risk calculated from age 35 for Indigenous

62
https://heartfoundation.org.au/images/uploads/publications/aust-cardiovascular-risk-charts.pdf,
63
Last accessed Jul 2016
 Progression of atherosclerosis
1. Endothelial cell injury and inflammation
2. Fatty streak
3. Hard / Fibrous plaque
4. Soft / Complicated plaque

64
1. Endothelial cell injury and inflammation
Injured endothelial cells:
Allows LDL to enter the subendothelium
Macrophages enter the subendothelium,
enhancing the inflammatory response
Unable to mediate vasodilation

65
Craft & Gordon, Understanding Pathophysiology 2nd ed 2015, Fig 23-11A
 Endothelial cells
Normal physiology: Pathophysiology:

Secrete nitric oxide (NO): Loss of nitric oxide

Vasodilating Vasoconstriction

Low levels of NO also promotes LDL entry into the vessel wall

66
 2. Fatty streak
LDL in the subendothelium is engulfed by
macrophages
Macrophages become foam cells

67
Craft & Gordon, Understanding Pathophysiology 2nd ed 2015, Fig 23-11B
 3. Fibrous / hard plaque
Macrophages release growth factors
Stimulate smooth muscle growth
Increased deposition of collagen
Loss of vasodilation

68
Craft & Gordon, Understanding Pathophysiology 2nd ed 2015, Fig 23-11C
 4. Soft and Complicated plaques
Thrombosis formation of a
Soft plaque: prone to rupture blood clot
The surface promotes thrombosis
Thrombus unstable, perfusion restored
quickly
Platelets promote vasoconstriction
Complicated plaque: Soft plaque + thrombus

69
Craft & Gordon, Understanding Pathophysiology 2nd ed 2015, Fig 23-11D
 Atherosclerosis
Soft plaque Fibrous / hard plaque

Lipid deposits covered Proliferation of connective

in fibrous cap tissue
Prone to rupture and Vessel less able to dilate
formation of a Calcification
complicated plaque

70
Damjanov, Pathophysiology, 2009, Fig 4-36
 Consequences of atherosclerosis
Heart: chest pain, heart attack, death
Brain: stroke, death
Arms and legs: peripheral artery disease,
gangrene and amputation
Kidneys: kidney failure
Genitals: erectile dysfunction, vaginal dryness

71
 Formation of an embolus

o Part of the thrombus

may break off the
plaque, becoming an
embolus

o Embolus travels
downstream and lodges
in a smaller diameter
vessel, blocking
perfusion to the organ

72
Gould, Pathophysiology for the Health Professions, 3rd edn, Fig 18-12e
 Prevention and management
Addressing risk factors, including dietary
Decreasing saturated and trans fats
Increasing mono-, poly-unsaturated fats and dietary
fibre
Medications
Antiplatelets
Anticoagulants
Lipid lowering
ACE inhibitors, angiotensin II blockers
73