Flashcards in Renal - Hypertension and renal vascular disease Deck (33):
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 artery stenosis
- primary hyperaldosteronism
- intrinsic renal disease
- defects in tubular sodium handling
- polycystic kidney disease
- Cushing's syndrome
- Liddle's syndrome
- congenital adrenal hyperplasia
- glucocorticoids (mineralocorticoid effect of exogenous and endogenous steroids)
- coarctation of the aorta (decreases renal perfusion, stimulates renin release)
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.
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
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
- 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)
ECG, ideally with echo to assess for LVH
- uric acid
- plasma and urinary catecholamines or vanillylmandelic acid (VMA) - phaeochromocytoma
- adrenal function tests - Cushings
- retinal angiography - renal artery stenosis
- 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
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
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.
Lifestyle advice for the hypertensive patient
Low salt diet recommended - aim for <6g/day, ideally 3g/day
Reduce caffeine intake
Stop smoking, drink less alcohol, weight loss, exercise, balanced diet
Step 1 treatment for hypertension
Patients <55 years old - ACEi
Patients >55 years old or Afro-Carribean - CCB
Step 2 treatment for hypertension
ACEi + CCB
Step 3 treatment for hypertension
Add thiazide diuretic (i.e. A + C + D)
NICE advocate using chlorthalidone or indapamide in preference to conventional thiazide diuretics (e.g. bendroflumethiazide)
Step 4 treatment for hypertension
Clinic BP > 140/90mmHg after optimal step 3 treatment as resistant hypertension.
Step 4 treatment:
- consider further diuretic treatment
- if potassium < 4.5 mmol/L add spironolactone 25mg OD
- if potassium > 4.5 mmol/L add higher dose thiazide like diuretic treatment
- if further diuretic treatment not tolerated, contraindicated or ineffective consider alpha or beta blocker
BP targets following treatment
Depend on age
< 80 years:
- clinic = 140/90mmHg
- ABPM/ HBPM = 135/85mmHg
> 80 years:
- clinic = 150/90mmHg
- ABPM/HBPM = 145/85mmHg
Role of direct renin inhibitors in hypertension management
Inhibiting renin blocks conversion of ATI --> ATII
Similar reduction in BP cf. ACEi/ ARBs
Adverse effects uncommon, diarrhoea occasionally seen
Only current role is in patients who fail with conventional anti-hypertensive medication
Why does renal artery stenosis cause hypertension?
Decreased renal perfusion stimulates the juxtaglomerular apparatus to release renin, which enhances ATII production. ATII causes hypertension by systemic vasoconstriction (increasing TPR) and by stimulating aldosterone release, which promotes salt and water retention.
Renal artery stenosis and renal impairment
ATII vasoconstricts the efferent arterioles more than the afferent arterioles. This reduces renal blood flow, but maintains GFR, so that filtration fraction is increased.
Inhibition of ATII (with ACEi) removes efferent vasoconstriction causing a fall in GFR. Microembolisation from an atherosclerotic plaque can contribute to renal damage. If only one kidney has a stenosed artery, plasma creatinine may be normal because of compensatory hyperfiltration by the other kidney.
Why does renal artery stenosis cause oedema?
Bilateral renal artery stenosis caused enhanced proximal tubular sodium reabsorption (due to alteration of Starlings forces). Contributory factors include a fall in renal blood flow, stimulation of proximal tubule NHE3 NA+/H+ exchanger by ATII and stimulation of distal tubular reabsorption of Na+ by aldosterone. Aldosterone also promotes potassium secretion which can cause hypokalaemia unless renal impairment is present.
Mild proteinuria can occur, possibly because ATII increases glomerular pore size. In unilateral RAS, salt and water balance are normalised by the other kidney.
Cause of renal artery stenosis
- atherosclerotic disease affecting proximal renal artery and accounts for most cases
- often vascular disease elsewhere
- usual risk factors for atherosclerosis - e.g. smoking, DM, hypertension, FHx, hyperlipidaemia
- fibromuscular dysplasia, esp women
- can occur as multiple bands separated by dilated segments, appearing as "beads on a string" on angiogram
Rare causes - Takayasu's arteritis, neurofibromatosis, pressure from renal artery aneurysms, and extrinsic pressure
Examination findings in renal artery stenosis
Risk factors for atherosclerosis or symptoms of vascular disease elsewhere
Rapid deterioration following administration of an ACEi or ARB is highly suggestive
Signs of vascular disease - bruits, aneurysms, or absent pulses
Bruits (caused by turbulent blood flow through a stenosed artery) may be heard over the kidneys
Pulmonary or peripheral oedema (if CCF) - "flash pulmonary oedema" (repeated episodes with only mild cardiac or renal impairment) suggest RAS
How should renal artery stenosis be investigated?
Diagnosis suggest by:
- Elevated urea and creatinina
- Different sized kidneys on USS
With unilateral disease, ischaemic damage reduces the size of the affected kidney.
Angiography definitive - MRA most common
Technetium labelled DTPA scan - Tc labelled DTPA is freely filtered at the glomerulus and neither secreted nor absorbed
- after injection, gamma camera produces a curve showing isotope accumulation in each kidney
- RAS - ATII increases proximal tubule reabsorption of sodium and water --> reduced urine flow --> delays peak and slows the downward phase
- administration of an ACE inhibitor during the renogram removes the effect of ATII (which also maintains GFR) and makes the test more sensitive
- Furosemide increases specificity by inhibiting distal salt reabsorption
Treatment of renal artery stenosis
ACEi and ARBs can reduce GFR, and a unilateral fall in GFR may be undetected by serum creatinine measurement. They can help with blood pressure control, but require careful monitoring.
Aspirin may help thrombus formation at the stenosis and statins reduce the progression of atherosclerotic lesions.
Percutaneous transluminal balloon angioplasty sometimes with stent insertion, can be undertaken
- response of hypertension variable
- usually has no beneficial effect on renal function
Renal embolisation for uncontrollable hypertension or nephrectomy to remove the source of renin
- success rate is higher for fibromuscular dysplasia, balloon angioplasty undertaken
How can cholesterol emboli affect the kidneys?
Detached fragments of atheroma in the aorta or renal arteries can embolize to the kidneys, especially after arterial surgery or angiography. Microemboli of cholesterol crystals and debris can provoke inflammation and fibrosis. Showers of these crystals can also cause LIVEDO RETICULARIS in the legs or microembolic lesions in the retina.
Acute renal infarction
Sudden occlusion of renal artery presents with acute loin pain with haematuria on dipstick, pain can sometimes be absent.
Severe hypertension common, but not always
LDH and CRP are raised.
- local atherosclerosis or by thromboemboli from distant source which cause occlusion in branch arteries with multiple parenchymal infarcts, visible on CT
Bilateral infarcts results in AKI with anuria (usually in patients with widespread vascular disease, evidence of aortic occlusion - absent pulses, reduced leg perfusion)
Rx - supportive, anticoagulation, stenting in some cases
Microvascular disorders associated with acute renal damage
= conditions association with acute damage and occlusion of small blood vessels (arterioles and capillaries)
Thrombotic microangiopathy (e.g. HUS and TTP)
Small vessel vasculitis
Microangiopathic haemolytic anaemia is a common feature of all, due to lysis of RBCs in damaged vessels.