📚 COMPLETE LECTURE-STYLE EXPLANATION: HYPERTENSION

(Based on Davidson's Principles & Practice of Medicine)

🔵 PAGE 1 - INTRODUCTION TO HYPERTENSION

What is Hypertension?

"The risk of cardiovascular diseases such as stroke and CAD is closely related to levels of BP."

"BP follows a normal distribution in the general population and there is no specific cut-off above which the risk of cardiovascular risk suddenly increases."

"The diagnosis of hypertension is therefore made when systolic and diastolic values rise above a specific threshold that corresponds to the level of BP at which the risk of cardiovascular complications and benefits of treatment outweigh the treatment costs and potential side effects of therapy."

"The British Hypertension Society classification, provided in Box 16.64, defines mild hypertension as existing when the BP is above 140/90 mmHg."

"The cardiovascular risks associated with high BP depend on the combination of risk factors in an individual, such as age, gender, weight, physical activity, smoking, family history, serum cholesterol, diabetes mellitus and pre-existing vascular disease."

• Smoking - damages blood vessel lining (endothelium), causes inflammation
• Diabetes mellitus - high blood sugar damages blood vessels chemically
• High cholesterol (hyperlipidaemia) - fat deposits build up in artery walls (atherosclerosis)
• Family history - genetic predisposition; if parents had heart attacks, your risk is higher
• Age - arteries naturally stiffen and narrow over time
• Obesity - extra body weight means the heart must pump blood to more tissue, increasing demand

🔴 PATHOGENESIS OF HYPERTENSION

(Why does high blood pressure develop?)

"Many factors may contribute to the development of hypertension, including renal dysfunction, peripheral resistance, vessel tone, endothelial dysfunction, autonomic tone, insulin resistance and neurohumoral factors."

"In more than 95% of cases, however, no specific underlying cause of hypertension can be found. Such cases are said to have essential hypertension."

🟢 BOX 16.65: CAUSES OF SECONDARY HYPERTENSION

• More circulating blood volume
• Increased sympathetic nervous activity
• Higher insulin resistance
• Physical compression of kidneys by fat tissue

• Combined oral contraceptive pill (oestrogen stimulates the liver to make more angiotensinogen)
• NSAIDs (like ibuprofen - cause sodium retention and reduce prostaglandins that dilate renal vessels)
• Steroids (like prednisolone - mimic aldosterone)
• Ciclosporin (used after organ transplants - causes renal artery constriction)
• Cocaine and amphetamines (strong sympathomimetics)

🟣 PATHOGENESIS (What happens to blood vessels)

"Hypertension has a number of adverse effects on the cardiovascular system. In larger arteries (>1 mm in diameter), the internal elastic lamina is thickened, smooth muscle is hypertrophied and fibrous tissue is deposited."

"The vessels dilate and become tortuous, and their walls become less compliant."

"In smaller arteries (<1 mm), hyaline arteriosclerosis occurs in the wall, the lumen narrows and aneurysms may develop. Widespread atheroma develops and may lead to coronary..."

🔵 PAGE 2 - CLINICAL FEATURES & INVESTIGATIONS

Clinical Features

"Hypertension is usually asymptomatic until the diagnosis is made at a routine physical examination or when a complication arises."

"Reflecting this fact, a BP check is advisable every 5 years in adults over 40 years of age to pick up occult hypertension."

"Sometimes clinical features may be observed that can give a clue to the underlying cause of hypertension. These include radio-femoral delay in patients with coarctation of the aorta, enlarged kidneys in patients with polycystic kidney disease, abdominal bruits that may suggest renal artery stenosis, and the characteristic facies and habitus of Cushing's syndrome."

• Moon face - round, puffy face from fat redistribution
• Buffalo hump - fat deposit at the back of the neck
• Central obesity - fat deposited around abdomen (apple-shaped)
• Purple striae - stretch marks on abdomen (wider and more purple than normal striae)
• Thin skin - bruises easily
• Proximal muscle weakness - difficulty climbing stairs or raising arms

"Examination may also reveal evidence of risk factors for hypertension, such as central obesity and hyperlipidaemia."

"Other signs may be observed that are due to the complications of hypertension. These include signs of left ventricular hypertrophy, accentuation of the aortic component of the second heart sound, and a fourth heart sound."

Retinal Changes in Hypertension (Fig. 16.76)

• Arterioles (tiny arteries) show increased reflectiveness ("silver wiring")
• Why: Normally blood in vessels absorbs light, giving a dull reflection. As walls thicken and become fibrosed/hyaline, they become more reflective - like a silver or copper wire. Copper wiring = earlier change, Silver wiring = more advanced.

• Grade 1 PLUS constriction of veins at arterial crossings ("arteriovenous nipping")
• Why: Where an artery and vein cross each other, they share a connective tissue sheath. When the artery wall thickens, it compresses the vein underneath it, making the vein appear narrowed or nipped at the crossing point.

• Grade 2 PLUS evidence of retinal ischaemia (flame-shaped or blot haemorrhages, and "cotton wool" exudates)
• Flame haemorrhages: Bleeding along nerve fibres, which follow a flame/spoke pattern
• Blot haemorrhages: Bleeding in deeper retinal layers, appearing as round blots
• Cotton wool spots (also called "soft exudates"): White, fluffy patches. NOT actually exudate (not fluid leaked out). They represent micro-infarcts - tiny areas where the nerve fibre layer has died from lack of blood supply. Nerve fibres swell and accumulate transport material, appearing white and fluffy. They fade in a few weeks.

• Grade 3 PLUS papilloedema - swelling of the optic disc (where the optic nerve enters the eye)
• This is the most severe grade and indicates malignant/accelerated hypertension
• Why does papilloedema occur? The optic nerve is surrounded by cerebrospinal fluid (CSF). When intracranial pressure rises (because of hypertensive encephalopathy or cerebral oedema), this pressure is transmitted to the optic nerve sheath, causing swelling at the disc.

🟡 PAGE 3 - INVESTIGATIONS

Why Investigate Hypertension?

"A decision to embark on antihypertensive therapy effectively commits the patient to life-long treatment, so readings must be as accurate as possible."

1. The BP is genuinely elevated (not just anxiety in the clinic)
2. No reversible underlying cause exists
3. You know their overall cardiovascular risk to guide how aggressively to treat

Blood Pressure Measurement (Box 16.67 - How to Measure BP)

"BP measurements should be made to the nearest 2 mmHg, in the sitting position with the arm supported, and repeated after 5 minutes' rest if the first recording is high."

"The cuff should contain a bladder that encompasses at least two-thirds of the arm circumference."

"Exercise, anxiety, discomfort and unfamiliar surroundings can all lead to a transient rise in BP. Sphygmomanometry, particularly when performed by a doctor, can cause a transient elevation in BP, which has been termed 'white coat hypertension.'"

Ambulatory Blood Pressure Monitoring (ABPM)

"A series of automated ambulatory BP measurements obtained over 24 hours or longer provide a better profile than a limited number of clinic readings and correlate more closely with actual target organ damage than casual BP measurements."

• It captures BP during normal daily activities
• It captures sleep BP (which should dip - the "nocturnal dip")
• It eliminates white coat effect
• It detects "masked hypertension" (normal in clinic, high at home)

Box 16.68 - Investigations for Hypertension

• Blood in urine (haematuria) - suggests glomerulonephritis or polycystic kidney disease
• Protein in urine (proteinuria) - suggests kidney damage; in hypertension this indicates nephropathy; also a feature of pre-eclampsia
• Glucose in urine (glycosuria) - suggests diabetes mellitus (a major cardiovascular risk factor)

• Urea and creatinine are waste products normally cleared by kidneys. If kidneys are damaged (hypertensive nephropathy), these rise - this is called renal impairment
• Hypokalemia (low potassium) - suggests primary hyperaldosteronism (Conn's syndrome) or diuretic therapy
• "Hypokalemic alkalosis may indicate primary hyperaldosteronism but is usually due to diuretic therapy" - Aldosterone causes the kidney to excrete potassium (low K+) and hydrogen ions (causing alkalosis = blood becomes more alkaline)

• To detect diabetes mellitus - a major cardiovascular risk factor and common cause of secondary hypertension

• Total cholesterol and HDL (High-Density Lipoprotein) - the "good" cholesterol
• The TC:HDL ratio is used in cardiovascular risk charts (Fig. 16.77)
• High total cholesterol + low HDL = high cardiovascular risk
• The risk charts plot SBP (Systolic Blood Pressure) vs TC:HDL ratio to estimate 10-year CVD risk

• Both hypothyroidism (underactive thyroid) and hyperthyroidism (overactive thyroid) can affect BP
• Hypothyroidism raises diastolic BP; hyperthyroidism raises systolic BP

• ECG detects LVH by showing increased voltage in specific leads
• Sokolow-Lyon criteria: S in V1 + R in V5/V6 > 35mm = LVH
• Also detects AF (atrial fibrillation) - a complication of hypertension causing irregular heartbeat

Box 16.69 - Specialised Investigation of Hypertension

• Echocardiography - Ultrasound of heart - more sensitive for LVH than ECG
• Renal imaging (ultrasound/doppler) - To detect renal artery stenosis (narrowed kidney arteries causing secondary hypertension) or polycystic kidneys
• Renal arteriography - X-ray with contrast dye injected into renal arteries - gold standard for diagnosing renal artery stenosis
• Plasma renin activity and aldosterone - To detect Conn's syndrome (primary hyperaldosteronism). In Conn's: aldosterone HIGH, renin LOW (because the adrenal is acting autonomously, independent of renin)
• Urinary catecholamines - Adrenaline, noradrenaline, and their metabolites (metadrenalines, VMA). Elevated in phaeochromocytoma
• Dexamethasone suppression test - For Cushing's syndrome (cortisol excess). In normal people, giving dexamethasone (a synthetic steroid) suppresses cortisol production. In Cushing's, cortisol stays high despite dexamethasone.

🟠 PAGE 4-5 - MANAGEMENT OF HYPERTENSION

Treatment Goals

"The objective of antihypertensive therapy is to reduce the incidence of adverse cardiovascular events, particularly stroke and heart failure."

"The optimum BP for reduction of major cardiovascular events has been found to be 139/83 mmHg, and even lower in patients with diabetes mellitus."

The Management Flowchart (Fig. 16.78)

• Check if accelerated hypertension or suspected phaeochromocytoma → Refer same day for specialist care (this is an emergency)
• Otherwise: Consider starting drug treatment immediately
• Offer ABPM or home BP monitoring (HBPM) to confirm

1. <135/85 mmHg (Normotensive) - Patient is normotensive (normal BP)! This was white coat hypertension. Check BP every 5 years; more often if close to 140/90. Look for signs of target organ damage.
2. 135-150/85-95 mmHg (Stage 1 Hypertension) - Mild hypertension. Only start drugs if target organ damage is present OR 10-year cardiovascular risk >20%. Otherwise: Offer lifestyle interventions first. If <40 years old: consider specialist referral (to exclude secondary causes in young patients).
3. ≥150/95 mmHg (Stage 2 Hypertension) - Moderate hypertension. Offer antihypertensive drug treatment directly.

• Offer lifestyle interventions
• Patient education for adherence
• Annual review of BP, medication, symptoms

Box 16.71 - Optimal Target Blood Pressures

🔵 NON-DRUG THERAPY (Lifestyle Changes)

"Appropriate lifestyle measures may obviate the need for drug therapy in patients with borderline hypertension, reduce the dose and/or the number of drugs required in patients with established hypertension, and directly reduce cardiovascular risk."

1. Correcting obesity - Every 1 kg of weight loss reduces BP by ~1 mmHg. Losing 10 kg can reduce SBP by 10 mmHg. More importantly, it reduces insulin resistance and sympathetic overactivity.
2. Reducing alcohol intake - Alcohol raises BP through mechanisms including cortisol release, sympathetic activation, and impaired sleep. Limit to <14 units/week (UK guidelines).
3. Restricting salt intake - Sodium (in salt) causes water retention, raising blood volume. Reducing salt to <6g/day can reduce SBP by 4-6 mmHg. The kidneys regulate sodium-water balance; less sodium = less water = lower BP.
4. Taking regular physical exercise - Exercise trains the cardiovascular system. Regular aerobic exercise reduces peripheral resistance, lowers resting heart rate, and promotes weight loss. 30 minutes of moderate exercise 5 days/week is recommended.
5. Increasing consumption of fruit and vegetables - High potassium content counters sodium; potassium promotes sodium excretion. Also high in antioxidants that protect endothelium.
6. Stopping smoking - Smoking doesn't actually chronically raise resting BP much, but it dramatically multiplies cardiovascular risk through endothelial damage, atherosclerosis, and thrombosis. Stopping smoking is THE most impactful cardiovascular risk reduction intervention.
7. Eating oily fish and adopting a low-saturated-fat diet - Reduces cholesterol and cardiovascular risk independent of BP change.

💊 DRUG THERAPY

1. Thiazide Diuretics

"The mechanism of action of these drugs is incompletely understood and it may take up to a month for the maximum effect to be observed."

2. ACE Inhibitors

"ACE inhibitors (enalapril 20 mg daily, ramipril 5-10 mg daily or lisinopril 10-40 mg daily) are effective and usually well tolerated."

1. Kidney releases Renin (when it senses low BP or low sodium)
2. Renin converts Angiotensinogen → Angiotensin I (inactive)
3. ACE (in lungs and vascular endothelium) converts Angiotensin I → Angiotensin II (very active)
4. Angiotensin II causes:
   • Vasoconstriction (directly constricts arteries)
   • Stimulates aldosterone release (causing sodium/water retention)
   • Stimulates ADH (antidiuretic hormone) release (more water retention)
   • Stimulates sympathetic nervous system

3. Angiotensin Receptor Blockers (ARBs)

"ARBs (irbesartan 150-300 mg daily, valsartan 40-160 mg daily) have similar efficacy to ACE inhibitors but they do not cause cough and are better tolerated."

4. Calcium Channel Antagonists (CCBs)

"Amlodipine (5-10 mg daily) and nifedipine (30-90 mg daily) are effective and usually well-tolerated antihypertensive drugs that are particularly useful in older people."

5. Beta-Blockers

"These are no longer used as first-line antihypertensive therapy, except in patients with another indication for the drug such as angina."

6. Other Vasodilators

"A variety of other vasodilators may be used. These include the α1-adrenoceptor antagonists prazosin (0.5-20 mg daily in divided doses), indoramin (25-100 mg twice daily) and doxazosin (1-16 mg daily), and drugs that act directly on vascular smooth muscle, such as hydralazine (25-100 mg twice daily) and minoxidil (10-50 mg daily)."

7. Aspirin

"Antiplatelet therapy is a powerful means of reducing cardiovascular risk but may cause bleeding, particularly intracerebral haemorrhage, in a small number of patients."

8. Statins

"Treating hyperlipidaemia can produce a substantial reduction in cardiovascular risk."

🔴 PAGE 6 - CHOICE OF DRUG & COMBINATION THERAPY

Box 16.72 - Influence of Comorbidity on Drug Choice

Combination Therapy

"Although some patients can be treated with a single antihypertensive drug, a combination of drugs is often required to achieve optimal control. Combination therapy may be desirable for other reasons; for example, low-dose therapy with two drugs may produce fewer unwanted effects than treatment with the maximum dose of a single drug."

• Step 1: ACE inhibitor or ARB (labeled 'A' in the chart)
• Step 2: Add a Calcium Channel Blocker ('C')
• Step 3: Add Thiazide diuretic ('D') - so A+C+D
• Step 4 (Resistant hypertension): Consider spironolactone, alpha-blocker, or beta-blocker + further specialist assessment

• Step 1: Calcium Channel Blocker OR Thiazide
• Then follow same steps

🔵 PAGE 7 - REFRACTORY & ACCELERATED/MALIGNANT HYPERTENSION

Refractory Hypertension

"Refractory hypertension refers to the situation where multiple drug treatments do not give adequate control of BP. Although this may be due to genuine resistance to therapy in some cases, a more common cause of treatment failure is non-adherence to drug therapy."

• Forget to take tablets
• Stop because of side effects without telling the doctor
• Take medication inconsistently

"Resistant hypertension can also be caused by failure to recognise an underlying cause, such as renal artery stenosis or phaeochromocytoma."

1. Check adherence (pill counts, pharmacy records, blood tests for drug levels)
2. Reassess for secondary causes
3. Review all medications including over-the-counter drugs (NSAIDs, decongestants)
4. Assess lifestyle factors

Accelerated (Malignant) Hypertension

"Accelerated or malignant hypertension is a rare condition that can complicate hypertension of any aetiology. It is characterised by accelerated microvascular damage with necrosis in the walls of small arteries and arterioles (fibrinoid necrosis) and by intravascular thrombosis."

• Grade 3 or 4 retinopathy (cotton wool spots/haemorrhages ± papilloedema)
• Rapidly rising BP with end-organ damage
• Renal dysfunction
• Hypertensive encephalopathy (brain involvement)

Management of Accelerated Hypertension

"In accelerated phase hypertension, lowering BP too quickly may compromise tissue perfusion due to altered autoregulation and can cause cerebral damage, including occipital blindness, or precipitate coronary or renal insufficiency."

• Watershed cerebral infarction (brain areas between vascular territories)
• Myocardial infarction
• Acute kidney injury

Box 16.70 - Hypertension in Old Age (Special Population)

Prevalence: Hypertension affects more than half of all people over 60 years (including isolated systolic hypertension).

Risks: Hypertension is the most important risk factor for myocardial infarction, heart failure and stroke in older people.

Benefit of treatment: Absolute benefit is greatest in older people (at least up to age 80 years). This makes sense - older people have higher baseline cardiovascular risk, so treatment prevents more events per 100 patients treated.

Target BP: Targets should be relaxed in older people to 150/90 mmHg.

Tolerance: Antihypertensives are well tolerated in older patients but need more care - postural hypotension, falls, electrolyte disturbances.

Drug of choice: Low-dose thiazides, but in the presence of coexistent disease such as gout or diabetes, other agents may be more appropriate.

📊 CARDIOVASCULAR RISK CHARTS (Fig. 16.77)

1. Choose the correct panel based on: sex (male/female), smoking status (smoker/non-smoker), age group (under 50/50-59/60+)
2. Find the intersection of: Y-axis = Systolic BP (SBP), X-axis = TC:HDL ratio (Total Cholesterol divided by HDL Cholesterol)
3. Read the colour:
   • Green = CVD risk <10% over next 10 years (low risk)
   • Yellow/Orange = CVD risk 10-20% (intermediate risk)
   • Red = CVD risk >20% (high risk)

🗂️ SUMMARY TABLE: Key Points for Exams