Hypertension CPC

10.11.06

Case 1
• Male aged 42, software salesman.
• Non-smoker and light drinker.
• Colleagues said he was prone to unpredictable fits of rage, described as "like apoplexy."
• Apparently fit and well.
• Suddenly died while driving his car.

• Autopsy conducted at request of coroner.
• Enlarged heart 450g (LVH).
• No obvious thrombus/infarct.

Phaeochromocytoma
• Tumour of adrenal medulla.
• Produces NA.
• Paroxysmal release.
• 10% bilateral/malignant.
• Large, pleomorphic cells with vascular architecture. Dense core granules on electron micrograph.

Case 2
• Female aged 48 presents with asymptomatic systemic hypertension of 150/110, discovered at insurance medical.
• Company director.
• FH: father died age 49 of stroke, vague history of large kidneys.

Investigations
• U + E:
-Creatinine 410.
-Urea 16.
-Potassium 4.8.
• Hb 11.1.
• Creatinine clearance 35 ml/min.
• USS: bilateral large kidneys.
• IVU: poor excretion and large kidneys.

Polycystic kidney, another renal cause of hypertension
• Autosomal dominant.
• 1:500 births.
• 10% chronic renal failure needing treatment.
• Middle-aged onset of symptoms.
• Associated with cysts of other organs (liver 40%) and berry aneurysms.

Case 3
• Male aged 59, PE teacher, generally well, goes to gym and does weights.
• Presents with severe abdominal pain of sudden onset ("tearing").
• Shocked: BP 100/55 on admission.
• Not anaemic, U + E normal.

• Abdominal wall become discoloured, purplish-brown.
• Angiogram shows leaking aortic aneurysm.
• Stabilised, then…
• Taken to theatre urgently.
• Open repair of aneurysm.
• Makes full recovery.

Aortic aneurysm
• Predisposing factors:
-Hereditary.
-Atheroma.
-Syphilis.
• Sites.
• Treatment:
-Open.
-Endovascular.
• Normal diameter ~ 1.5-2.5cm.
• Risky >5cm.
• Likely to rupture in 12 months >6cm.
• Screening programme for people at risk (+FH).
• Endovascular repair somewhat better results than open (current BMJ data).

BP
• Measurement errors.
• 24-hour recording shows wide variation.
• Spikes possible in moments.

Case 4
• Female, aged 55, florist.
• Presents with severe headaches, not relieved by aspirin.
• Noticed swollen ankles lately.
• BP 190/140.
• U + E: sodium 148, potassium 5.1, creatinine 380, urea 16.8.
• Renal biopsy shows:
-Necrotising arteriolitis.
-Hyperplastic arteriolitis (onion-skinning).
-Necrotising glomerulonephritis.
• Fails to respond to aggressive antihypertensive therapy.
• Develops stroke - becomes comatose.
• CT brain shows subarachnoid haemorrhage.
• Some recovery occurs, but left with severe deficit.

Systemic Hypertension

10.11.06

What is it?
• What is normal BP?
• Usually given in mmHg as 100 + age, but only in Western populations.
• What is abnormal level?
• Very variable definition - some debate about whether to treat ostensibly healthy population who are not symptomatic but may be at slight risk of complications.
• Diastolic >90 usually given as threshold level.
• Systolic >140 over period also - hypertension.

Prevalence/types
• Gives prevalence ~25%, increasing with age >50 years.
• More common in females (But less severe in older female group).
• 90-95% is essential type.
• Most of secondary type due to renal disorders (but others possible: endocrine, vascular, Neurogenic).
• Malignant (accelerated) hypertension: can occur in both essential and secondary types - ~5% hypertensive patients develop this.

Mechanisms
• BP = cardiac output x peripheral resistance.
• Concept of autoregulation - especially brain and kidney (but to some extent, all vessels).
• Cardiac output influenced by volume and cardiac activity factors.

Peripheral resistance influenced by:
• Neural (α, β adrenergic).
• Local (autoregulation, ionic, pH etc.)
• Dilators (prostagladins, kinins).
• Constrictors (angiotensin-II, catecholamine, thromboxane, leukotrienes).
• Also by atheroma affecting compliance of aorta.
• Coarctation.

Derangements
• Renin-angiotensin system: normally accurately controlled feedback mechanism.
• Increased renin important in:
-Unilateral renal artery stenosis.
-Malignant hypertension.
-Vasculitis.
-Pyelonephritis.
-JGA tumours, Wilms' tumour/carcinoma.
-Some cases of chronic renal failure of various causes.
• Sodium homeostasis: as well as angiotensin II, glomerular filtration rate and natriuretic factors have bearing on this.
• Sodium retention most important factor in hypertension of chronic renal failure, with which it is strongly associated.

Mechanisms of essential hypertension
1. Genetic (twins, blood relatives).
-Polygenic inheritance.
-?Role of imprinting.
2. Environment: dietary sodium most important?
-Variation of blood pressure with sodium intake locally.

Possible reasons
• Loss/defect of sodium excretion facility.
• Defect of sodium transport in cell membranes.
• Increased sympathetic response to stress/neurogenic factors.

Renal artery stenosis
• Accounts for 2-4% all hypertension, but treatable.
• Type works by JGA stimulation proportional to degree of stenosis.
• 70% cases due to atheromatous plaque at origin of artery.
• Fibromuscular dysplasia can also occur.

Other causes of secondary hypertension
• Renal.
-Acute glomerulonephritis.
-Renal polycystic disease.
-Renal involvement by vasculitis.
• Endocrine.
-Exogenous hormones.
-Steroid-producing tumours.
-Thyroid.
-Phaeochromocytoma.
• Neural.
-Acute stress.
-Sleep apnoea.
-Raised intracranial pressure.
-Psychological.
§Note: blood pressure can be lowered in some people by biofeedback methods.

Effects of hypertension: kidney
• Benign nephrosclerosis.
-Small granular kidneys with narrowed vessels and resultant ischaemic atrophy, glomerulosclerosis and tubular atrophy.
-Fibroelastic hyperplasia in larger arteries.
-Does not usually cause renal failure but will have reduced reserve.

Cerebral effects of benign hypertension
• Intracerebral haemorrhage + subarachnoid.
• Lacunae (minute infarcts in deep portions of brain e.g. basal ganglia and white matter).
• Subcortical leukoencephalopathy: diffuse loss of hemispheric white matter leading to dementia (probably ischaemic).

Hypertensive heart disease
• Left ventricular hypertrophy, usually of concentric type. LV >200g. May occur even at 140/90 i.e. 25% of population.
• Heart undergoes hypertrophy as result of increased workload.
• Eventually, leads to ischaemic fibrosis and decompensation.
• Can be diagnosed only in absence of other causes e.g. aortic stenosis.
• Coronary atherosclerosis interacts with (and is worsened by) hypertension.
• If blood pressure controlled, some evidence hypertrophy may regress. Especially true of ACE inhibitors.

Malignant hypertension - clinical features
• Diastolic >130, papilloedema, encephalopathy, renal failure and cardiac insufficiency.
• Often present with headaches/scotomas.
• May have hypertensive crises.
• Real emergency. Now 50% 5-year survival - much improved from previous rate.

Pathogenesis
• Very high levels of renin, angiotensin II and aldosterone.
• Interacts with endothelial damage to cause intravascular thrombosis, with more ischaemia and vicious circle.
• Sometimes coagulation may come first.
• Renal failure results from profound ischaemia.

Effects: kidney
• Malignant nephrosclerosis.
-Strongly correlated with previous benign hypertension/renal disease of another type.
-2 main changes.

Effects: brain
• Encephalopathy: associated with malignant hypertension, eclampsia and acute nephritis.
• Headache, drowsiness, stupor and coma.

The Cardiovascular System In Its Context

6.11.06

Hypertension
• ABC of Hypertension: The Pathophysiology of hypertension, BMJ, 322: 912-916.
• Up to 5% patients with hypertension have it as secondary to some other disease e.g. renal disease.
• Rest have "essential hypertension."

Story so far…
Stroke volume

Cardiac output


Heart rate

• Intrinsic (Starling's law - "more in, more out").
• Extrinsic (principally autonomic.)

Postulated mechanism
• Increased sympathetic activity:
-Leads to increased cardiac output.
-And peripheral vasoconstriction (to protect capillary beds).
• Drop in blood flow triggers rennin-angiotensin system.

Evidence
• Cross transplantation studies show essential hypertension has origins in kidneys.
-Human and animal studies.
• Little evidence "stress" involved.
-But, of course, drugs that decrease sympathetic activity decrease blood pressure.

Control
BRAIN
Volume ANS
Pressure
Chemicals ADH

HEART BODY


Angiotensin

LOCAL BLOOD FLOW

Pressure
• Sensed by baroreceptors - in carotid arteries and aortic arch.
• Increase in pressure causes decrease in sympathetic activity.
• Decrease in pressure causes increase in sympathetic activity.

Volume
• Sensed by atrial volume receptors.
• Decrease in volume causes:
-Increase in ADH secretion.
-Decrease in ANP secretion.

Local blood flow (kidney)
Decreased renal blood flow


Monitored by JGA cells


Renin production


Angiotensin Angiotensin I


Converting enzyme

Angiotensin II

Sodium resorption
Aldosterone
Potassium secretion

Vasoconstriction

Hormones
• Angiotensin II = vasoconstrictor.
• Aldosterone increases vascular sensitivity to angiotensin II.
• ADH increases water resorption.
• ANP decreases sodium secretion.

Module 2.06

Ignorance Is Bliss?
6.11.06 - 17.11.06.