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

Aetiology of Hypertension Primary – 90-95% of cases – also termed “essential” of “idiopathic” Secondary – about 5% of cases Renal parenchymal (2-5%) or renovascular disease Endocrine disease Phaeochomocytoma Cushing syndrome Conn syndrome Acromegaly and hypothyroidism Coarctation of the aorta Iatrogenic Hormonal / oral contraceptive NSAIDs

Renal parenchymal disease Acute and chronic glomerulonephritis Polycystic kidney disease Diabetic nephropathy Pyelonephritis Obstructive uropathy Neoplasms Renal trauma Radiation nephritis

Renal parenchymal disease Most forms of renal disease are associated with hypertension. The prevalence of hypertension in chronic renal parenchymal disease varies with each. Hypertension is most evident with glomerular diseases, in which 70% to 80% of patients are affected, including diabetic nephropathy (DN), membranous glomerulonephritis (MGN), membranoproliferative glomerulonephritis (MPGN) and focal segmental glomerulonephritis (FSGN). Minimal change nephropathy (MCN) is a notable exception. Tubulointerstitial disorders such as analgesic nephropathy, chronic interstitial nephritis (CIN), medullary cystic diseases, and chronic reflux nephropathies are less commonly associated with hypertension. 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 Coarctation of the aorta Iatrogenic Hormonal / oral contraceptive NSAIDs

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

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 (0.1-0.6 %) Cushings syndrome Conn’s syndrome Acromegaly and hypothyroidism Coarctation of the aorta Iatrogenic Hormonal / oral contraceptive NSAIDs

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” Frequency of signs and symptoms (%) of pheochromocytoma

PHEOCHROMOCYTOMA diagnostic 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

PHEOCHROMOCYTOMA imaging 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).

MRI (coronal and sagittal sections): 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 removal Preoperative 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 activity measured 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 Hyperaldosteronism Should 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

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 Cushing’s syndrome (0.1-0.6%) Conn’s syndrome Acromegaly and hypothyroidism Coarctation of the aorta Iatrogenic Hormonal / oral contraceptive NSAIDs

Cushing’s Syndrome Hypertension occurs in about 80% of patients; Urinary free cortisol If 24h UFC>100 µg/ml: measure plasma ACTH

Hypothyroidism Hyperthyroidism Acromegaly Both hypertension (particularly diastolic) and hypotension are common; Hyperthyroidism Accompanied by systolic hypertension, especially in the elderly; Acromegaly 25-50% exhibit elevated blood pressure