9.1 Cardiovascular Function and Disease

What does each component of the ECG (P, QRS, ST, T) represent?

P wave = atrial depolarisation (electrical activity through upper chambers). QRS complex = ventricular depolarisation. ST segment = ventricular contraction with no current flow (normally flat/isoelectric). T wave = ventricular repolarisation/resetting.

How is iron stored in the body, and in which tissues are the major stores?

Iron is stored mainly in the liver (~1000 mg as ferritin/haemosiderin), erythrocytes (~2000 mg as haemoglobin), and the reticuloendothelial system (~80 mg). Plasma transferrin carries only ~3 mg in transit.

What is the role of hephaestin in iron transport?

Hephaestin is a transmembrane ferroxidase that oxidises Fe²⁺ to Fe³⁺ as iron exits the enterocyte. Fe³⁺ then binds to plasma transferrin for transport in the blood.

What is the role of the lymphatic system in relation to the cardiovascular system?

It collects excess tissue (interstitial) fluid and returns it to the cardiovascular system, maintaining fluid balance.

Describe the four stages of atherosclerosis development.

Stage 1: LDL infiltrates the intima of healthy vessels. Stage 2: Monocytes infiltrate to clear LDL (inflammatory response). Stage 3: Macrophages engulf oxidised LDL → foam cells → atherosclerotic plaque. Stage 4: Inflammation causes plaque rupture → thrombus formation → vascular occlusion.

What happens when an unstable plaque ruptures?

Platelet activation, adhesion, and aggregation at the rupture site; activation of the clotting cascade; formation of an occlusive thrombus that can completely block the coronary artery, causing an MI.

How do arteries, capillaries, and veins differ structurally and functionally?

Arteries (thick smooth muscle wall) carry blood away from the heart and regulate pressure. Capillaries (one-cell-thick wall) allow exchange of gases and nutrients with tissues. Veins (thin walls, valves) return blood to the heart.

What cholesterol level and blood pressure threshold are used as risk cut-offs for heart disease?

Cholesterol >5.2 mmol/L and blood pressure >140/90 mmHg are the thresholds cited as risk factors for coronary heart disease.

What ECG changes suggest myocardial infarction versus angina?

Angina: ST depression (horizontal or downsloping). Infarct/STEMI: ST elevation. NSTEMI/unstable angina: inverted T waves or ST depression. Pericarditis: saddle-shaped ST elevation. Pathological Q waves indicate myocardial necrosis.

What are the two main circuits of the cardiovascular system?

The pulmonary circuit (heart → lungs → heart) and the systemic circuit (heart → all body tissues → heart). Pulmonary arteries carry deoxygenated blood to the lungs; systemic arteries carry oxygenated blood to tissues.

Which population groups in Australia have the highest rates of CVD hospitalisation and death?

Lower socioeconomic groups, Aboriginal and Torres Strait Islander peoples, and those living in remote areas have disproportionately high rates of CVD hospitalisation and death.

What is the role of duodenal cytochrome B reductase in iron absorption?

It reduces extracellular Fe³⁺ (ferric) to Fe²⁺ (ferrous) so that it can be transported into the enterocyte via DMT1.

What is the difference between NSTEMI and STEMI?

NSTEMI: partial coronary occlusion → subendocardial infarction; ECG shows T-wave inversion or ST depression. STEMI: complete occlusion → transmural (full-thickness) infarction; ECG shows ST elevation and raised troponins. STEMI requires immediate reperfusion.

What is haemochromatosis and what are its consequences?

Iron overload disorder, most commonly hereditary (HFE gene). Excess iron accumulates in parenchymal cells of the liver, pancreas, heart, joints, and gonads, causing tissue damage and haemosiderosis.

List six major risk factors for heart disease.

Family history, dyslipidaemias, smoking (~19% of MI risk), hypertension (>140/90 mmHg, ~13%), diabetes, and menopause. High cholesterol (>5.2 mmol/L) is associated with ~46% and physical inactivity with ~37% of heart disease cases.

What is ferroportin 1 and what is its function?

Ferroportin 1 is a transmembrane channel that exports Fe²⁺ from enterocytes into the bloodstream. Its function is inhibited by hepcidin in states of iron overload.

In iron deficiency, how do serum iron, TIBC, transferrin saturation, and ferritin change?

Serum iron ↓; total iron-binding capacity (TIBC) ↑; transferrin saturation ↓; serum ferritin ↓; soluble transferrin receptor ↑. Oral iron treatment normalises haemoglobin.

What is thrombosis and what three things can cause it?

Thrombosis is the formation of a blood clot within a vessel. It can result from: 1) turbulent blood flow; 2) inflammatory processes; 3) rupture of an unstable atherosclerotic plaque.

Name the three categories of causes of iron deficiency anaemia.

1) Increased iron requirements (growth, pregnancy, erythropoietic therapy); 2) Increased iron loss/blood loss (GI, genitourinary, respiratory tracts; blood donation); 3) Decreased intake/absorption (poor diet, malabsorption, gastric surgery, IRIDA).

What is cardiac ischaemia and what is its most common cause?

Ischaemia is cell damage/death due to hypoxia when coronary blood supply falls below a critical level. The most common cause is coronary artery disease/atherosclerosis. It ranges in severity from angina to acute myocardial infarction (Acute Coronary Syndrome spectrum).

Where in the body is dietary iron absorbed, and what form must it be in?

Iron absorption is an active process in the duodenum. Only the reduced ferrous form (Fe²⁺) can be transported into enterocytes via DMT1 (divalent metal transporter 1), not the oxidised ferric form (Fe³⁺).

What is myocardial infarction and what underlies it?

MI is necrosis of heart tissue caused by loss of blood supply (ischaemia). The underlying pathology is atherosclerosis causing narrowing of coronary arteries and reduced perfusion. It typically presents as chest pain (angina pectoris).

What are three key statistics about cardiovascular disease burden in Australia?

CVD kills one Australian every 12 minutes; affects 1 in 6 Australians (~3.7 million people); in 2017 there were ~61,800 acute coronary events (~169/day). Lower socioeconomic groups, Aboriginal and Torres Strait Islander peoples, and those in remote areas have the highest hospitalisation and death rates.

What are the four key functions of the cardiovascular system?

1) Transporting O₂ from lungs to cells; 2) Transporting nutrients from intestines to cells; 3) Carrying waste products to kidneys, liver, and lungs; 4) Ensuring cell viability. The heart pumps ~5 L of blood per minute.

How do oxidised LDL particles contribute to plaque formation?

LDL particles enter the intima and become oxidised. Oxidised LDL recruits monocytes (via adhesion molecules on endothelial cells) that differentiate into macrophages. Macrophages engulf oxLDL via scavenger receptors, becoming lipid-laden foam cells that form the plaque core.

What is hepcidin and what does it do?

Hepcidin is a 25-amino acid peptide hormone released by the liver. When iron levels are high (overload), the liver increases hepcidin production, which inhibits ferroportin 1 and blocks Fe²⁺ export from enterocytes into the blood.

How does iron overload differ biochemically from iron deficiency?

In iron overload: serum iron ↑, ferritin ↑, transferrin saturation ↑; TIBC is normal or ↓; soluble transferrin receptor ↓. Oral iron treatment is inappropriate/contraindicated.

What is the difference between a stable and an unstable atherosclerotic plaque?

Stable plaque: thick fibrous cap over a necrotic lipid core — less prone to rupture. Unstable plaque: thin fibrous cap, foam cells secreting tissue factor, local inflammatory infiltrate (neutrophils, T-cells, macrophages) — prone to rupture and thrombosis.

What are four clinical uses of an ECG?

1) Diagnose unexplained chest pain (e.g. MI, pericarditis); 2) Investigate symptoms of heart disease; 3) Check pacemaker function; 4) Monitor heart health in patients with risk factors (hypertension, diabetes, high cholesterol, smoking).