secondary hypertension

SECONDARY HYPERTENSION

DEFINITION

• Essential, primary, or idiopathic hypertension is defined as high BP in which secondary causes or mendelian (monogenic) forms are not present

• High BP – repeatedly measured BP exceeding 140/90 mmHg, i.e. a systolic BP above 140 and/or diastolic BP above 90

Aetiology of Hypertension

• Primary – 90-95% of cases – also termed “essential” of “idiopathic”

• Secondary – about 5% of cases– Renal or renovascular disease– Endocrine disease

• Phaeochomocytoma• Cushings syndrome• Conn’s syndrome• Acromegaly and hypothyroidism

– Coarctation of the aorta– Iatrogenic

• Hormonal / oral contraceptive• NSAIDs



• Secondary – about 5% of cases– Renal parenchymal (2-5%)or renovascular disease– Endocrine disease

• Phaeochomocytoma• Cushing syndrome• Conn syndrome• Acromegaly and hypothyroidism



Renal parenchymal disease

• Acute and chronic glomerulonephritis

• Polycystic kidney disease

• Diabetic nephropathy

• Pyelonephritis

• Obstructive uropathy

• Neoplasms

• Renal trauma

• Radiation nephritis

Renal parenchymal disease

CIN – chronic interstitial nephritis; APKD – adult-onset polycystic kidney disease; MCN - minimal change nephropathy; MGN – membranous glomerulonephritis; DN – diabetic nephropathy; MPGN – membranoproliferative glomerulonephritis; FSGN – focal segmental glomerulonephritis

Candidate pathophysiologic mechanisms related to hypertension in parenchymal renal disease

Hypertension in parenchymal renal disease: major target organ manifestations

Hypertension in parenchymal renal disease

Hypertension in parenchymal renal disease:CONCLUSIONS

• Hypertension may result from renal disease that reduces functioning nephrons;

• Evidence shows a clear relationship between high blood pressure and end-stage renal disease;

• BP should be controlled to 130/85 mmHg (125/75 mmHg in patients with proteinuria in excess of 1g/24 h)

Aetiology of Hypertension• Primary – 90-95% of cases – also termed “essential” of

“idiopathic”

• Secondary – about 5% of cases– Renal parenchymal

or renovascular disease (0.3-3%)– Endocrine disease

• Phaeochomocytoma• Cushings syndrome• Conn’s syndrome• Acromegaly and hypothyroidism



RENAL ARTERY STENOSIS(RAS)

• Atherosclerotic RAS (>90% of cases): involves the ostium and the proximal portion of the main renal artery with plaque extending into the perirenal aorta

• Fibromuscular dysplasia (10% of cases): typically seen in young and middle-aged females. As opposed to atherosclerotic RAS, fibromuscular dysplasia typically affects the distal two thirds of the main renal artery

RENAL ARTERY STENOSIS:screening and diagnostic studies

Renal duplex sonography Magnetic resonance angiography Renal artery arteriography Captopril renography

RENAL ARTERY STENOSIS:renal duplex sonography

Stenoses over 60%:

• Peak systolic velocity (PSV) >150-180 cm/sec

• Renal-aortic ratio >3.5

Prognostic value:

• Resistance index (RI): RI=(1-EDV)/PSVx100;

if RI>80 no benefit after revascularization

RENAL ARTERY STENOSIS:MR angiography

Strong sides:

• Provides images of the renal arteries, 3D-reconstruction, plaque characterization and hemodynamic information

• Gadolinium (contrast agent): non-nephrotoxic

Weak sides: high cost and limited availability

RENAL ARTERY EVALUATION:MR angiography (3D-reconstruction)

RENAL ARTERY EVALUATION:contrast angiography (the “gold” standard)

Fibromuscular dysplasia: “string of beads” appearance

Atherosclerotic RAS with poststenotic dilatation

What is your diagnosis ?

RENAL ARTERY STENOSIS:treatment

• BP control

• Antiplatelet, lipid-lowering therapy, and beta-blockers, if appropriate

• No ACE-inhibitors in severe RAS !

RENAL ARTERY STENOSIS:treatment

Percutaneous or surgical revascularization, if:

● Resistant or poorly controlled hypertension and unilateral or bilateral renal artery stenosis

● Renal artery stenosis and recurrent flash pulmonary edema for which there is no readily explainable cause

● Chronic renal failure and bilateral renal artery stenosis or renal artery stenosis to a solitary functioning kidney

● Sonographic renal longitudinal length >7cm




• Phaeochomocytoma (0.1-0.6 %)• Cushings syndrome• Conn’s syndrome• Acromegaly and hypothyroidism



PHEOCHROMOCYTOMA“frequently searched for, but rarely found”

• About 90 % of pheochromocytomas are located within the adrenal glands;

• 10% are bilateral;• 10% are malignant;

• 10% are extra-adrenal;

• Extra-adrenal pheochromocytomas develop in paraganglion chromaffin tissue of the sympathetic nervous system; of them, 40% are not diagnosed, 5% are multiple;

• overall, nearly 98% of pheochromocytomas are found in the abdomen

Frequency of signs and symptoms (%) of pheochromocytoma

PHEOCHROMOCYTOMA“the great mimic”

PHEOCHROMOCYTOMAdiagnostic techniques

Biochemical tests High pressure liquid chromatography:

• Plasma catecholamines: noradrenaline, adrenaline;

• Free plasma fractionated metanephrines: normetanephrine, metanephrine;

• Urinary catecholamines (24h)• Urinary fractionated metanephrines (24h)

Spectrophotometry:• Total metanephrines (24h urine);• Vanillylmandelic acid (24h urine)

PHEOCHROMOCYTOMA

Sensitivity and specifity of biochemical tests for diagnosis of pheochromocytoma

PHEOCHROMOCYTOMAimaging techniques

• Duplex sonography;

• Magnetic resonance imaging (MRI);

• Computed romography (CT);

• 123I – meta-iodo-benzyl-guanidine scanning (123I-MIBG)

PHEOCHROMOCYTOMA

Sonography :

• Sonographic appearances are those of a well-defined homogeneous hypoechoic mass in approximately 50 pet cent of patients.

• However the mass may be complex or even cystic (16 pet cent) and hyperechoic to the renal parenchyma (approximately 20 pet cent).

PHEOCHROMOCYTOMA

MRI (coronal and sagittal sections):

• Magnetic resonance (MR) imaging is equally sensitive to CT and lends itself to in vivo tissue characterization, which is not possible with CT;

• MR imaging is nearly 100% sensitive and around 70% specific.

• Preferred for the localisation of extra-adrenal tumours or tumours during pregnancy, in children, or in patients with allergies to contrast

PHEOCHROMOCYTOMA

CT:

• accurately detects tumors larger than 1.0 cm and has a localization precision of approximately 98%, although it is only 70% specific;

• since CT scanning and MRI have similar sensitivities (90–100%) and specificities (70–80%), MRI is the preferred procedure

PHEOCHROMOCYTOMA

123I-MIBG scanning:

• increased specificity (95–100%), as compared with CT or MRI;

• provides both anatomic and functional characterization;

• Relevant in patients with multiple, extra-adrenal, malignant (metastatic) tumors

PHEOCHROMOCYTOMA: laparoscopic removalPreoperative Management (10-14 days)

Purpose: to prevent catecholamine induced, serious, and potentially life-threatening complications during surgery, including hypertensive crises, cardiac arrhythmias, pulmonary oedema, and cardiac ischemia;

BP should be reduced to below 160/90 mm Hg for at least 24h;

orthostatic hypotension should be present, but blood pressure in the upright position should not fall below 80/45 mm Hg;

there should be no more than one ventricular extrasystole every 5 min;

and the electrocardiogram should show no S-T segment changes and T-wave inversions for 1 week;

PHEOCHROMOCYTOMA:Management

• Phenoxybenzamine, a long acting alpha-adrenergic blocker, is the mainstay of medical treatment to control BP. A total dose of 1 mg/kg is sufficient in most patients.

• An alpha-blocker Doxazosin in increasing doses from 1 to 16 mg once a day.

•A beta-adrenoceptor blocker (eg,propranolol 40 mg three times daily or atenolol 25–50 mg once daily) could be included after several days of alpha-adrenergic blockade.

• Adequate salt and fluid intake lowers the risk of orthostatic hypotension.

PHEOCHROMOCYTOMA:Management

•Should substantial rises in blood pressure still take place during surgery, these can be controlled by bolus or by continuous infusion of phentolamine, sodium nitroprusside, or a shortacting calcium antagonist (eg, nicardipine);

• Tachyarrhythmias can be treated by infusion of a shortacting -adrenoceptor blocker (eg, esmolol).

PHEOCHROMOCYTOMA

Sensitivity and specifity of biochemical tests for diagnosis of pheochromocytoma

Conn’s Syndrome (primary hyperaldosteronism)

• Should be considered in any hypertensive pt with muscle weakness, polydipsia, andor hypokalemia;

• 75% - adrenal adenoma;

• 25% - adrenal hyperplasia

• Rarely – adrenocortical cancer

Primary Hyperaldosteronism• Screening for hyperaldosteronism should include

plasma aldosterone and plasma renin activitymeasured in morning samples

• Plasma aldosterone:renin ratio: normally <20; diagnostic cut-off value >30;

• Aldosterone excretion rate during salt loading, captopril, or spironolactone test (the captopril test may be less useful in blacks because of the high prevalence of low plasma renin activity)

• Adrenal CT, MRI

Primary HyperaldosteronismShould be differentiated from

• Secondary hyperaldosteronism in patients with renal failure, CHF, essential hypertension

• Monogenic forms of hypertension (pseudohyperaldosteronism):

Liddle’s syndrome (autosomal-dominant disorder, characterized by low-renin, low-aldosterone, low-potassium volume-expanded hypertension)

Gordon’s syndrome (autosomal-dominant disorder, characterized by low-renin, low-aldosterone, high-potassium volume-expanded hypertension)

Primary Hyperaldosteronism

TREATMENT

1. Medical• Spironolactone, a competitive aldosterone antagonist• Amiloride, a potassium-sparing diuretic

• Glucocorticoids (in glucocorticoid-remediable form)

2. Surgical, if appropriate




• Phaeochomocytoma

• Cushing’s syndrome (0.1-0.6%)Conn’s syndrome • Acromegaly and hypothyroidism



Cushing’s Syndrome

• Hypertension occurs in about 80% of patients;

• Urinary free cortisol

• If 24h UFC>100 µg/ml: measure plasma ACTH

Hypothyroidism

• Both hypertension (particularly diastolic) and hypotension are common;

Hyperthyroidism

• Accompanied by systolic hypertension, especially in the elderly;

Acromegaly

• 25-50% exhibit elevated blood pressure

secondary hypertension

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