Renal - Hypertension and renal vascular disease Flashcards
Definition of hypertension
Blood pressure greater than 140/90mmHg.
Can damage vessels and organs
Cause identified = “secondary” hypertension
No cause identified = “primary/ essential” hypertension
ABP = CO X TPR CO = SV X HR
ABP = (SV X HR) X TPR
Key determinants of hypertension are total peripheral resistance (determined in turn by degree of arteriolar constriction) and circulatory volume (increases preload, which affects stroke volume).
Causes of secondary hypertension
Renal causes:
- renal artery stenosis
- primary hyperaldosteronism
- intrinsic renal disease
- defects in tubular sodium handling
- polycystic kidney disease
Endocrine causes:
- phaeochromocytoma
- Cushing’s syndrome
- Liddle’s syndrome
- congenital adrenal hyperplasia
- acromegaly
Others:
- glucocorticoids (mineralocorticoid effect of exogenous and endogenous steroids)
- NSAIDs
- pregnancy
- coarctation of the aorta (decreases renal perfusion, stimulates renin release)
- COC
Renal artery stenosis causing hypertension
Reduces renal blood flow and GFR, stimulating renin release and angiotensin II production. ATII causes hypertension by vasoconstriction and stimulation of aldosterone release and sodium retention.
If both kidneys affected, the hypervolaemia and hypertension eventually restores renal perfusion and renin levels fall slightly. If only one kidney affected, hypertension increases GFR. This promotes sodium excretion by the healthy kidney, but the stenosed kidney remains underperfused and continues to produce high renin levels.
No fluid retention in unilateral renal artery stenosis.
Primary hyperaldosteronism
Cause of secondary hypertension - 1-2% of cases.
Excess aldosterone increases renal sodium retention and potassium excretion –> hypervolaemia –> hypertension
Renin production is suppressed because renal perfusion pressure and sodium chloride delivery to the macula densa are increased.
Mechanism by which intrinsic renal disease causes hypertension
Any renal disease can cause hypertension
Severe renal impairment reduces sodium excretion and causes hypervolaemia and hypertension - “salt sensitive” because increased by salt intake
Milder renal impairment, perceived renal hypoperfusion promotes renin secretion and ATII mediated vasoconstriction. This hypertension is NOT salt sensitive and is termed salt resistant.
Defects in tubular handling causing secondary hypertension
Pseudohyperaldosteronism type 2 due to WNK1 or WNK4 mutations cause distal tubular NCC sodium chloride co-transporter overactivity with excess sodium retention, hyperkalaemia and hypertension.
Liddle’s syndrome of pseudohyperaldosteronism also causes excess sodium retention, hypokalaemia and hypertension.
What two mechanisms explain the raised increased peripheral resistance in primary hypertension?
1) High renin/ salt resistant/ dry essential hypertension
- raised serum renin levels for their body sodium content
- -> ATII release with vasoconstriction, aldosterone secretion and sodium retention
- filtration fraction and sodium excretion increase to a greater extent and the patient can become hypovolaemic
- HTN is “salt resistant” because salt excretion is not impaired
- High renin and ATII correlate with vascular injury and end organ damage
- High ATII down regulates nephrin –> proteinuria
- High renin HTN responds best to inhibition of renin angiotensin II axis with ACEi’s, ARBs or beta blockers
2) Low renin/ salt sensitive/ wet essential hypertension
- renal sodium and water retention, suppresses renin production
- hypertension worsens with salt intake
- sodium retention may be caused by increased sympathetic adrenergic activity or a deficit in sodium coupled transport
- excess sodium –> vasoconstriction by altering smooth muscle calcium fluxes
- Rx = sodium restriction, diuretics, alpha blockers and CCBs
Diagnosing hypertension
Clinic reading of >= 140/90mmHg indicates HTN
Patient should be offered ABPM or HBPM
1) < 135/85mmHg = not hypertension, no Rx needed
2) >= 135/85mmHg = STAGE 1 HTN, Rx if <80 AND
- target organ damage
- established cardiovascular disease
- renal disease
- diabetes
- 10 year cardiovascular risk equivalent to 20% or greater
3) >=150/95mmHg = STAGE 2 HTN, Rx ALL patients regardless of age
- clinic BP should be >=160/100mmHg
If BP >180/110mmHg immediate treatment should be initiated
- if evidence of papilloedema or retinal haemorrhages then NICE recommend same day treatment by specialist
Investigations in hypertensive patients
Urinalysis (assess renal damage) FBC Serum electrolytes Lipid profile Fasted glucose ECG, ideally with echo to assess for LVH
Specialist investigations:
- uric acid
- plasma and urinary catecholamines or vanillylmandelic acid (VMA) - phaeochromocytoma
- adrenal function tests - Cushings
- retinal angiography - renal artery stenosis
Patterns:
- hypokalaemia suggests primary hyperaldosteronism
- paired plasma renin and aldosterone, useful if hypokalaemia and hypertension
i) BOTH raised = secondary hyperaldosteronism (e.g. high renin in renal artery stenosis)
ii) Low renin, high aldosterone = primary hyperaldosteronism (Conn’s syndrome)
iii) BOTH low = other explanation for high mineralocorticoid activity, e.g. raised glucocorticoids
Rx with ACEi, ARBs and diuretics can slightly elevate the ratio of renin to aldosterone, but a very low or undetectable plasma renin should raise suspicion of primary hyperaldosteronism.
Renal complications of hypertension
Microalbuminuria and dipstick proteinuria early signs of hypertensive nephropathy
- BP control slows rate of renal damage
Groups most at risk of renal damage - elderly, obese, black patients, patients from Indian subcontinent who are also diabetic
Raised pressure damages renal vessels
- interlobular arteries, muscular walls replaced by sclerotic tissue
- afferent arteriole wall undergoes hyalinization - subintimal deposition of lipids and glycoproteins exuded from plasma
- exposure of glomerular capillary endothelium to high pressure —> reduces glomerular blood flow and filtration, promotes proteinuria
- inflammatory proteins exuded from plasma –> glomerular sclerosis or ischaemic atrophy
Cardiovascular complications of hypertension
High vascular resistance increases afterload on heart –> LVH.
Also accelerates atherosclerosis
Retinopathy associated with hypertension
Graded according to severity:
- Grade 1 = arterial spasm, tortuous arteries, silver wire appearance
- Grade 2 = arteriovenous nipping, veins appear narrowed as arteries pass over them
- Grade 3 = heamorrhage, flame haemorrhages; lipid extravasation causes exudates, hard exudates are old but soft exudates, or cotton wool spots, indicate acute severe hypertension
- Grade 4 = papilloedema, swollen optic disc
Malignant hypertension
Severe hypertension with grade 3 or 4 retinal changes. Can arise anew or as a complication of essential or secondary hypertension.
Central feature is renal vessel damage, usually caused by hypertension. Damage reduces renal blood flow, triggering renin secretion, which promotes further hypertension and sodium retention.
Damage to endothelium can cause fibrinoid necrosis - fibrin enters the blood vessels, triggering cell proliferation, vessel occlusion and ischaemia.
Clinical features of malignant hypertension
Headache
Visual disturbance
SOB from cardiac problems
Renal impairment is common - haematuria and proteinuria
Damaged vessels can harm RBCs –> microangiopathic haemolytic anaemia
Treatment for malignant hypertension
ACEi’s, ARBs or beta blockers
Care is required because patients can have renal artery stenosis.
Diuretics promote sodium excretion
Hypertensive encephalopathy, pulmonary oedema, or severe acute renal disease may require i.v. treatment with sodium nitroprusside, hydralazine, labetalol or a nitrate infusion.
