Aorta and arteries
The aorta is an elastic bag that catches each stroke of blood and pushes it out again between beats; the arteries beyond it are muscular taps that set how hard the heart has to push.
What it normally does
The aorta stretches in systole and recoils in diastole (the Windkessel effect). That recoil is what drives blood forward between beats, so organs get a fairly steady stream instead of squirts. The difference between systolic and diastolic pressure is the pulse pressure, normally around 40 mmHg. Diastolic pressure matters most to the left coronary bed: the contracting myocardium squeezes its intramural branches shut in systole, so the left ventricular myocardium is perfused mainly in diastole, off that recoil pressure. The right coronary artery, running over a lower-pressure right ventricle, is perfused through both phases.
when the aorta stiffens, systolic pressure spikes and diastolic pressure sags at the same time — a wide pulse pressure. The low diastolic number is not a reassuring number: it is the pressure that was perfusing the left coronary bed.
The small arteries and arterioles are the resistance vessels. Their smooth muscle constricts to noradrenaline (alpha-1 receptors) and to angiotensin II (AT1 receptors), and sustained constriction depends chiefly on calcium entering through L-type calcium channels (with a smaller contribution from calcium released inside the cell and from rho-kinase sensitising the machinery to whatever calcium is present). To a good approximation mean arterial pressure = cardiac output x systemic vascular resistance (strictly, mean arterial minus right atrial pressure), so tone in these vessels is most of what sets blood pressure.
blood pressure can be lowered at any point on that chain — cut angiotensin II signalling, block the calcium channel, or unload volume — and the antihypertensive classes map straight onto it.
The inner lining (endothelium) is a single cell layer that resists platelet adhesion, releases nitric oxide to relax the muscle underneath, and forms a barrier that limits how much LDL cholesterol enters the wall. Some LDL crosses even a healthy endothelium; injury raises how much gets in and how long it stays.
endothelial injury is the first step of atherosclerosis, and it explains why the same risk factors — smoking, LDL, hypertension, diabetes — produce disease in coronary, carotid and leg arteries alike.
The wall has three layers: a thin inner intima, a thick media of elastin, collagen and smooth muscle, and an outer adventitia. The media carries the load. By Laplace's law, circumferential wall tension rises with pressure and with radius (T is roughly pressure x radius), and wall stress is that tension spread over the wall thickness — so a wide, thin-walled vessel is under far more strain than a narrow one at the same pressure.
once the media is damaged, both of the big aortic catastrophes follow from it: the wall bulges and the bulge feeds itself (aneurysm), or blood splits the media apart along its length (dissection).
What goes wrong
- Hypertension from raised arteriolar tone← from “The small arteries and arterioles are the resi…”
The resistance vessels sit constricted — sympathetic drive and angiotensin II push tone up — while salt and water retention loads extra volume on top. Take the two limbs of mean pressure = output x resistance: resistance rises with no compensating fall in output, so pressure rises through the whole arterial tree upstream of the arterioles. The left ventricle now ejects against a higher load and thickens (concentric hypertrophy), and the sustained pressure batters the endothelium, feeding the problems below. In most people no single cause is found (primary hypertension); secondary causes are worth thinking about in the young, the severe, and the sudden.
Raised systemic vascular resistance with preserved output. Asymptomatic, diagnosed on repeated or ambulatory readings, clinic threshold 140/90. Treatment decided on absolute CVD risk, except that severe hypertension and end-organ disease are treated regardless. Consequences: LV hypertrophy, accelerated atherosclerosis, aneurysm and dissection.
You would find: Usually nothing at all — it is found on a cuff, not by symptoms. Repeat readings, home readings or ambulatory monitoring come before anyone is labelled hypertensive, because a single high clinic reading may be white-coat effect. Australian practice takes clinic blood pressure at or above 140/90 mmHg as hypertension, with a daytime ambulatory average at or above about 135/85 mmHg as the equivalent. Whether to treat is then judged mainly on absolute cardiovascular risk (the Australian CVD risk calculator), not on the number alone — but that is not a rule without exceptions: markedly raised pressure, around 160/100 mmHg and above, and established cardiovascular, kidney or diabetic end-organ disease are treated on their own account.
- Stiff aorta and wide pulse pressure (isolated systolic hypertension)← from “The aorta stretches in systole and recoils in …”
With age, and faster with hypertension, elastin in the aortic media fragments and is replaced by stiffer collagen. The aorta can no longer stretch to absorb the stroke volume, so systolic pressure spikes higher; and having stored little elastic energy, it has little to give back, so diastolic pressure sags. The pulse pressure widens. Reflected pressure waves also return from the periphery earlier, arriving in late systole rather than diastole, which augments the systolic peak instead of supporting the diastolic pressure. The low diastolic pressure matters most, because that is the pressure perfusing the left coronary bed.
Age-related elastin loss in the aortic media. Systolic up, diastolic down, pulse pressure wide. It is the commonest hypertension pattern over 60 and it carries real risk — do not dismiss a normal-looking diastolic. Differentiate from aortic regurgitation and high-output states.
You would find: An older patient with a blood pressure like 175/65 mmHg and a bounding pulse with a sharp upstroke. Wide pulse pressure is the finding, and it means a stiff pipe, not a strong heart. Do not confuse it with the collapsing (water-hammer) pulse of aortic regurgitation, which widens pulse pressure by leaking blood back out of the aorta rather than by stiffening it. Other causes of a wide pulse pressure include a high-output state such as thyrotoxicosis, severe anaemia or an arteriovenous fistula.
- Atherosclerosis← from “The inner lining (endothelium) is a single cel…”
Smoking, high LDL, hypertension and diabetes injure the endothelium, so its barrier and anti-adhesive functions fail. LDL enters the intima in excess and is oxidised; monocytes are recruited, become macrophages, eat it and turn into foam cells; a lipid core builds under a fibrous cap formed by smooth muscle and collagen. A stable plaque narrows the lumen, and once the narrowing is severe — roughly 70% of diameter in a coronary artery — flow reserve is used up, so flow is adequate at rest but not on exertion. If the cap ruptures or erodes, the thrombogenic core and subendothelial collagen are exposed, platelets adhere and a thrombus forms, and the artery can occlude in minutes. Plaques tend to form where flow is disturbed: branch points, bifurcations and the inner curve of bends.
Endothelial injury, LDL retention and oxidation, foam cells, lipid core under a fibrous cap. Stable plaque causes demand-limited symptoms; cap rupture with thrombosis causes the acute event. Degree of stenosis predicts angina; plaque composition predicts infarction.
You would find: Depends on the artery. Coronary: exertional chest tightness relieved by rest. Legs: calf pain on walking that stops with rest (intermittent claudication), absent pedal pulses, ankle-brachial index below 0.9 (an index above about 1.4 means non-compressible calcified vessels, common in diabetes and chronic kidney disease, and cannot be used to exclude disease). Carotid: a bruit, transient ischaemic attack or stroke. An occlusive rupture presents abruptly as myocardial infarction or stroke rather than as gradual worsening — though many ruptures are clinically silent, heal, and simply make the plaque bigger.
- Abdominal aortic aneurysm← from “The wall has three layers: a thin inner intima…”
Chronic inflammation, proteolysis and atherosclerosis destroy elastin and collagen in the media, so the wall gives and the aorta balloons out — conventionally called an aneurysm once the infrarenal aorta reaches about 30 mm. Laplace's law then makes this self-perpetuating: a wider radius means more wall tension at the same pressure, which stretches it further, and stress rises again as the wall thins. Rupture happens when wall stress exceeds wall strength.
Infrarenal aorta 30 mm or more. Laplace makes expansion self-feeding. Male smokers over 65. Surveillance by ultrasound; repair thresholds around 55 mm in men, 50 mm in women, or fast growth. Ruptured AAA is pain plus hypotension plus a pulsatile mass — do not wait for all three.
You would find: Silent until it is not — usually an incidental pulsatile, expansile abdominal mass or an ultrasound finding. Rupture is sudden abdominal or back pain with hypotension and a pulsatile mass. The highest-risk group in Australia is men over 65 who have smoked; Australia has no national AAA screening program, so most are found incidentally. Small aneurysms are followed by ultrasound; repair is generally considered from about 55 mm in men and about 50 mm in women, or with rapid growth (of the order of 10 mm a year), because beyond that the yearly rupture risk starts to outweigh the risk of repairing it.
- Aortic dissection← from “The wall has three layers: a thin inner intima…”
A tear in the intima lets pressurised blood enter the media and split it along its length, creating a false lumen. The flap propagates with each beat, driven by the pressure and by how fast pressure rises (dP/dt). It causes harm by what it shears past: branch arteries are sheared off or compressed (stroke, absent limb pulse, ischaemic kidney, gut or spinal cord); or, if it involves the aortic root, the root dilates and the valve leaflets lose their commissural support, so they prolapse and the valve leaks (acute aortic regurgitation); or it ruptures into the pericardium (tamponade) or the pleural space. Hypertension is the main risk factor; connective tissue disease — Marfan syndrome (fibrillin-1), Loeys-Dietz, vascular Ehlers-Danlos — and bicuspid aortic valve are the young-patient versions. Stanford type A involves the ascending aorta and is a surgical emergency; type B spares it and is usually managed medically unless complicated.
Intimal tear, blood into the media, false lumen propagating with dP/dt. Tearing pain maximal at onset, inter-arm gradient over 20 mmHg, new AR murmur, wide mediastinum. Type A to theatre, type B usually medical. Control rate before pressure.
You would find: Sudden severe tearing or ripping chest pain radiating through to the back, often with a blood pressure difference of more than 20 mmHg between the arms, a new early diastolic murmur, or a widened mediastinum on chest x-ray. The pain is typically maximal at onset, whereas infarction pain more often builds. CT aortography is the usual confirmatory test in a stable patient.
What we give, and how it works
Open a drug to see what it binds, what that does to the cell, and what you then see in the patient.
- Binds
- Angiotensin converting enzyme on endothelial cell surfaces (ACE inhibitors), or the AT1 receptor on arteriolar smooth muscle and adrenal zona glomerulosa (sartans)
- Which does
- Less angiotensin II is made, or less of it signals. Arteriolar smooth muscle loses a constrictor stimulus and relaxes; less aldosterone is released, so less sodium and water are retained.
- So you see
- Systemic vascular resistance and blood pressure fall over days to weeks, with no reflex tachycardia because the baroreflex is not being driven hard and sympathetic facilitation by angiotensin II is reduced. Left ventricular hypertrophy regresses over months.
- And the same mechanism causes
- Angiotensin II is what constricts the efferent glomerular arteriole to hold up filtration pressure, and it drives aldosterone. Remove both and creatinine can rise and potassium climb — a small early creatinine rise that plateaus is the mechanism working, but a steep rise suggests filtration was depending on that efferent tone (bilateral renal artery stenosis, volume depletion). Blocking fetal renin-angiotensin signalling causes oligohydramnios and fetal renal failure, which is why both classes are contraindicated in pregnancy.
- Handling
- Potassium and kidney function are checked a week or two after starting or increasing the dose, and the drugs are withheld during acute dehydrating illness.
Catches people out: A dry cough is the classic reason people stop an ACE inhibitor — ACE also degrades bradykinin, so blocking it lets bradykinin and substance P accumulate in the airway. Sartans cause it far less often, though not never, which is why the usual response to the cough is to switch. Angioedema is rare but can be life-threatening; it is much less frequent with sartans but has been reported after switching, so it is not a free swap. Combining an ACE inhibitor with a sartan is avoided: dual blockade adds hyperkalaemia and acute kidney injury without improving outcomes.
- Binds
- The L-type (Cav1.2) calcium channel in vascular smooth muscle; the dihydropyridines are far more selective for vascular than for cardiac channels, unlike verapamil and diltiazem
- Which does
- Calcium entry falls, so calcium-calmodulin activation of myosin light chain kinase falls and the actin-myosin cross-bridging that maintains tone cannot be sustained. The arteriole dilates.
- So you see
- Systemic vascular resistance and blood pressure fall. Because the vascular selectivity spares the sinoatrial and atrioventricular nodes, heart rate is not slowed — it may rise a little through the baroreflex, especially with shorter-acting agents.
- And the same mechanism causes
- Ankle swelling, and it is not fluid overload. These drugs dilate the precapillary arteriole but not the postcapillary venule, so more of the arterial pressure is transmitted to the capillary and fluid is driven into the interstitium. Because it is a capillary pressure problem rather than a volume problem, it does not respond to a diuretic; it eases when the dose is reduced or an agent that also dilates the venous side is added. Flushing and headache follow from the same arteriolar dilation.
- Handling
- Ankle oedema is dose-dependent, so recognising it as mechanism rather than heart failure prevents an unnecessary diuretic.
Catches people out: Ankle swelling is common and is frequently misread as heart failure. Any change of dose or agent is the prescriber's call — the point to take from here is the physiology, not a course of action.
- Binds
- HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway, in the hepatocyte
- Which does
- Intracellular cholesterol synthesis falls, SREBP-2 is activated, and the hepatocyte upregulates LDL receptors on its surface.
- So you see
- Circulating LDL cholesterol falls; over years plaque lipid content falls, inflammation settles and the fibrous cap thickens, so fewer plaques rupture. The benefit is fewer events, not fewer symptoms.
- And the same mechanism causes
- The mevalonate pathway also supplies coenzyme Q10 and the isoprenoids used to prenylate signalling proteins in myocytes, which is the usual explanation for statin-associated muscle symptoms. Aching proximal muscles are the common complaint; genuine myopathy with a raised creatine kinase is uncommon and rhabdomyolysis rare, and the risk rises with anything that raises statin exposure.
- Handling
- Muscle symptoms are far more often tolerable than dangerous, and blanket cessation loses a large benefit — which is why the symptom is investigated rather than assumed.
Catches people out: Because patients feel nothing, adherence is the main practical problem. In Australia lipid-lowering is directed mainly by absolute cardiovascular risk rather than by the cholesterol number alone — with the important exceptions that established cardiovascular disease, familial hypercholesterolaemia and a markedly raised LDL are treated in their own right.
- Binds
- Platelet COX-1 (aspirin) and the platelet P2Y12 ADP receptor (clopidogrel, a prodrug activated by hepatic CYP2C19)
- Which does
- Thromboxane A2 synthesis, and ADP-driven amplification of activation, are lost. Because the platelet has no nucleus it cannot replace the acetylated enzyme or the blocked receptor, so the effect lasts that platelet's lifetime of about 7 to 10 days and recovers only as new platelets appear.
- So you see
- Aggregation on a ruptured cap is blunted, so an occlusive thrombus is less likely — fewer myocardial infarctions and strokes in people who already have arterial disease.
- And the same mechanism causes
- The same blockade of platelet aggregation everywhere means bleeding — gastrointestinal and intracranial in particular. Aspirin adds a second, separate mechanism of gastric injury: COX-1 in gastric mucosa also makes the prostaglandins that maintain mucus, bicarbonate and mucosal blood flow, so blocking it removes mucosal defence at the same time as it removes clotting.
- Handling
- The antiplatelet effect outlasts the drug by days because it is irreversible, which is what matters around surgery or bleeding.
Catches people out: This is for people who already have arterial disease. Aspirin is not routinely used for primary prevention in otherwise healthy people in Australia, because at low absolute risk the bleeding harm offsets the benefit.
- Binds
- Beta-1 adrenoceptors on cardiac myocytes and the sinoatrial node (esmolol and metoprolol are beta-1 selective; labetalol blocks beta-1, beta-2 and alpha-1)
- Which does
- Less Gs-coupled signalling means less cyclic AMP, less protein kinase A activity, and less calcium cycling — the node fires more slowly and the ventricle contracts less forcefully and less rapidly.
- So you see
- Heart rate, contractility and the rate of rise of aortic pressure all fall. Accepted practice aims at a heart rate around 60 beats per minute and the lowest systolic pressure — conventionally about 100 to 120 mmHg — that still perfuses brain, kidneys and heart.
- And the same mechanism causes
- The same negative inotropy and chronotropy that protect the aorta reduce cardiac output, so hypotension, bradycardia and heart block can follow — and that is dangerous here, because a dissection involving the root may already have caused acute aortic regurgitation or tamponade, where output depends on rate. Beta-2 blockade with labetalol can provoke bronchospasm in asthma.
- Handling
- Esmolol is titratable and very short-acting (its effect wears off within minutes), which is why it is favoured when the haemodynamic tolerance is uncertain.
Catches people out: Order matters, and the reason is pure physiology: rate and contractility are controlled first, vasodilation second. A vasodilator given alone drops pressure, the baroreflex answers with a tachycardia and a more forceful ejection, and the resulting rise in dP/dt can extend the dissection — the opposite of the intent. This is emergency management by a senior team; it appears here to explain the mechanics of the flap, not as anything to act on.
Systolic pressure is what the ventricle generates; diastolic pressure is what the aorta gives back. So 175/65 in an 80-year-old is a stiffness problem, not a strong heart — and the left coronary bed, perfused mainly in diastole because systole squeezes its intramural branches shut, is the one paying for that low second number. Carry the same two-layer thinking into the aortic catastrophes: Laplace's law explains why an aneurysm widens until it tears, and dP/dt explains why a dissection propagates — which is why one is sized and watched and the other is rate-controlled before it is vasodilated.
Now test whether it stuck
Reading this through is not the same as being able to reconstruct it. Every question in the bank is free, with a full debrief on each option.