Disorders of Blood Flow & Blood Pressure Regulation – Comprehensive Study Notes

Blood Vessel Architecture

• Every vessel, regardless of size, possesses three concentric tunics:
  • Tunica interna (intima) – endothelium + thin basement membrane, directly adjacent to the lumen.
  • Tunica media – concentric layers of smooth-muscle cells interwoven with elastic fibres (elastic lamellae in large arteries).
  • Tunica externa (adventitia) – connective tissue sheath anchoring the vessel to surrounding structures.
• Comparative morphology of vessels:
  • Elastic (conducting) artery – thick media rich in elastic lamellae; dampens the systolic pulse.
  • Muscular (distribution) artery – prominent internal elastic lamina; thick smooth-muscle media allows vasomotion.
  • Arteriole – ≤2 elastic lamellae; critical resistance vessels.
  • Capillary (continuous, fenestrated, sinusoidal) – endothelium + basement membrane ONLY; primary exchange site.
  • Venule / vein – thinner media, large irregular lumen, abundant valves preventing retrograde flow.
  • Arteries have thicker walls, higher intraluminal pressure, a folded intima and greater elasticity, whereas veins display larger luminal diameters, lower pressure and valves.

Disorders of the Arterial System

1. Dyslipidaemia

• "Imbalance" of circulating lipid fractions. Lipid categories:
  • Triglycerides – glycerol + $3$ FA; metabolic fuel.
  • Phospholipids – structural backbone of lipoproteins, membranes, myelin.
  • Cholesterol – sterol with membrane, steroid-hormone, bile-salt roles.
• Hyperlipidaemia = elevation of ≥1 lipid class.
• Transported by lipoproteins:
  • Chylomicrons (exogenous TG) desirable $<150$ mg/dL, high >$200$.
  • VLDL (endogenous TG) desirable $<150$ mg/dL. • LDL (major cholesterol carrier) optimal $<100$ mg/dL, high >$160$.
  • HDL anti-atherogenic $40–60$ mg/dL (low <$40$). • Total-C desirable $<200$, high >$240$ mg/dL.

Hypercholesterolaemia

• Defined as serum cholesterol ≥$240\,\text{mg/dL}$; confers ↑ risk of MI, stroke, other atherosclerotic events.
• Aetiology:
  • Primary (familial) – defective LDL-receptor gene ➜ decreased LDL clearance.
  • Nutritional / lifestyle – high saturated-fat diet, obesity ➜ ↓ HDL receptor activity.
  • Secondary (metabolic) – Diabetes mellitus elevates all atherogenic lipoproteins.
• Clinical clues (usually asymptomatic): CAD, PAD, tendon/tuberous xanthomas at extremely high levels, neuropathic paraesthesias, dyspnoea, confusion.

2. Atherosclerosis

• Literally “paste hardening” of the arteries; fibrofatty plaque formation within the intima of large & medium muscular arteries.
• Canonical lesion sequence (simplified 4-step):
  $1.$ Endothelial injury/dysfunction (HTN, smoking, hyper-LDL) ➜ ↑ permeability & leukocyte adhesion.
  $2.$ Monocyte migration ➜ uptake of oxidised-LDL ➜ foam-cell formation (macrophages + lipid-laden SMCs create fatty streak – even observable in infants).
  $3.$ SMC proliferation & extracellular-matrix deposition ➜ fibrous cap over lipid core.
  $4.$ Progressive plaque growth ± calcification, necrotic core, thinning cap ➜ rupture / thrombosis / embolisation.
• Major risk factors:
  • Hypercholesterolaemia, cigarette smoking, hypertension.
  • Positive family history of premature CHD (first-degree ♂<$55$, ♀<$65$).
  • Age (♂ ≥$45$, ♀ ≥$55$).
  • Low HDL <$40$ mg/dL, elevated C-reactive protein (CRP), ↑ homocysteine.

Complications & Organ-specific Sequelae:

• Ischaemic narrowing ➜ angina, claudication.
• Acute occlusion/rupture ➜ MI, stroke.
• Thrombo-embolisation.
• Aneurysmal dilation (wall weakening).
• Sites & outcomes:
  • Cerebral – stroke; Carotid – TIA/stroke.
  • Coronary – angina/MI.
  • Aorta – aneurysm.
  • Renal – renovascular hypertension.
  • Iliac/femoral/tibial – peripheral vascular disease (PVD).

3. Vasculitis

• Immune-, infectious- or trauma-mediated inflammation of arterial, capillary, venous walls, causing necrosis & lumen compromise.

4. Peripheral Arterial Disorders

• Acute arterial occlusion – embolus / trauma ➜ 6 Ps (pain, pallor, pulselessness, paresthesia, paralysis, polar).
• Atherosclerotic occlusive disease – lower-leg vessels of men $60–70$ yrs; chronic claudication, rest pain.
• Thromboangiitis Obliterans (Buerger) – non-atherosclerotic vasculitis of medium arteries (foot, hand) in ♂ $25–40$ heavy smokers; episodic ischaemia, ulceration.
• Raynaud disease/phenomenon – paroxysmal digital vasospasm, often healthy young females; triggered by cold/emotion ➜ pallor→cyanosis→rubor sequence.

5. Aneurysms

• Localized permanent dilation of an artery/vein with wall weakness.
• Types:
  • Berry – small saccular dilations at Circle of Willis branchpoints; risk of subarachnoid haemorrhage.
  • Fusiform & saccular (true) – circumferential or asymmetric dilations of thoracic/abdominal aorta; enlarge gradually.
  • Dissecting (false) aneurysm – intimal tear ➜ blood tracks within media generating a longitudinal channel; acute, lethal without rapid control.

Disorders of Venous Circulation

• Primary varicose veins – superficial saphenous reflux from valve failure; precipitated by prolonged standing, pregnancy, obesity.
• Secondary varicosities / chronic venous insufficiency – deep-vein obstruction or incompetent perforators ➜ oedema, stasis dermatitis, ulcers.
• Venous thrombosis (DVT) – Virchow triad: stasis + hypercoagulability + endothelial injury; inflammatory response.

Regulation of Blood Pressure

• Adequate perfusion vs. vascular damage trade-off.
  • Hypotension ➜ impaired nutrient/oxygen delivery, waste removal.
  • Hypertension ➜ endothelial injury, accelerates atherosclerosis, risk of haemorrhage.

Hypertension Categories

• Essential (primary/idiopathic) – chronic BP elevation with no overt secondary cause (~$90–95\%$ of all cases).
• Secondary – consequence of another disorder; potentially curable.
• Malignant / hypertensive emergency – diastolic >$120$ mmHg + acute target-organ injury.

Pathogenesis of Essential Hypertension

• Renal mechanisms: disordered sodium & water handling ➜ ↑ blood volume; hyperactive RAAS (renin-angiotensin-aldosterone system) ➜ vasoconstriction & Na⁺ retention.
• Sympathetic nervous system: chronic ↑ tone ➜ peripheral resistance.
• Modifiers: genetics, race (↑ prevalence & severity in African-Americans), age, diabetes mellitus.
• Lifestyle contributors: high salt intake, obesity, physical inactivity, excess alcohol, combined oral contraceptives.

Consequences / Target-Organ Damage

• Left-ventricular hypertrophy (LVH) – adaptive response to afterload; major predictor of IHD, CHF, arrhythmia.
• Ischaemic heart disease, cerebrovascular disease, aortic dissection, renal insufficiency/ESRD, hypertensive retinopathy.

Risk Factors Recap

• Advancing age, male sex / African ancestry, positive family history, high-sodium diet, tobacco, alcohol, obesity, dyslipidaemia.

Secondary Hypertension Examples

• Renal parenchymal / renovascular – impaired perfusion ➜ ↑ renin.
• Endocrine:
  • Hyperaldosteronism (Conn) or glucocorticoid excess (Cushing).
  • Phaeochromocytoma – adrenal medulla tumour secreting catecholamines.
• Coarctation of the aorta – congenital narrowing proximal to renal arteries ➜ upper-body hypertension.

Malignant Hypertension

• Rapid BP rise (often younger African-American ♂, pregnancy HTN, renal/collagen disorders).
• Diastolic >$120$ mmHg, papilloedema, encephalopathy, acute nephropathy; requires emergent reduction.

Orthostatic (Postural) Hypotension

• Diagnostic criterion: sustained fall ≥$20$ mmHg systolic or ≥$10$ mmHg diastolic within $3$ min of standing or $60^{\circ}$ tilt.
• Causes: volume depletion, antihypertensive/vasodilator drugs, ageing (baroreflex impairment), prolonged bed rest, autonomic neuropathies (diabetes), spinal cord injury, Parkinson disease, cerebrovascular accidents.

Hypertension in Pregnancy

• Categories:
  • Preeclampsia–eclampsia (new-onset HTN + proteinuria ± seizures).
  • Chronic hypertension (pre-existing).
  • Chronic HTN with superimposed preeclampsia.
  • Gestational (transient) hypertension.