1. SECONDARY HYPERTENSION

2. 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

3. 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

5. 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

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

7. 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

8. Candidate pathophysiologic mechanisms related to hypertension in parenchymal renal disease

10. Hypertension in parenchymal renal disease: major target organ manifestations

11. Hypertension in parenchymal renal disease

12. 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)

14. 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

15. 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

16. RENAL ARTERY STENOSIS: screening and diagnostic studies
Renal duplex sonography
Magnetic resonance angiography
Renal artery arteriography
Captopril renography

17. RENAL ARTERY STENOSIS: renal duplex sonography
Stenoses over 60%:
Peak systolic velocity (PSV) > cm/sec
Renal-aortic ratio >3.5
Prognostic value:
Resistance index (RI):
RI=(1-EDV)/PSVx100;
if RI>80 no benefit after revascularization

18. 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

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

20. RENAL ARTERY EVALUATION: contrast angiography (the “gold” standard)
Fibromuscular dysplasia:
“string of beads” appearance
Atherosclerotic RAS with
poststenotic dilatation

21. What is your diagnosis ?

22. RENAL ARTERY STENOSIS: treatment
BP control
Antiplatelet, lipid-lowering therapy, and beta-blockers, if appropriate
No ACE-inhibitors in severe RAS !

23. 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

24. 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

25. 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

26. Frequency of signs and symptoms (%) of pheochromocytoma
PHEOCHROMOCYTOMA “the great mimic”
Frequency of signs and symptoms (%) of pheochromocytoma

27. 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)

28. PHEOCHROMOCYTOMA
Sensitivity and specifity of biochemical tests for diagnosis of pheochromocytoma

29. PHEOCHROMOCYTOMA imaging techniques
Duplex sonography;
Magnetic resonance imaging (MRI);
Computed romography (CT);
123I – meta-iodo-benzyl-guanidine scanning (123I-MIBG)

30. 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).

31. 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

32. 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

33. 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

34. 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;

35. 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.

36. 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).

37. PHEOCHROMOCYTOMA
Sensitivity and specifity of biochemical tests for diagnosis of pheochromocytoma

38. 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

39. 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

40. 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)

41. Primary Hyperaldosteronism
TREATMENT
1. Medical
Spironolactone, a competitive aldosterone antagonist
Amiloride, a potassium-sparing diuretic
Glucocorticoids (in glucocorticoid-remediable form)
2. Surgical, if appropriate

42. 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 ( %)
Conn’s syndrome
Acromegaly and hypothyroidism
Coarctation of the aorta
Iatrogenic
Hormonal / oral contraceptive
NSAIDs

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

44. 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