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- 2. CONTENTS • What isthe renin angiotensin system? • Role it plays in hypertension • Laboratory tests
- 3. WHAT IS IT? •A hormone system • Regulate blood pressure and fluid balance • Involve kidney ,liver and lungs
- 4. IMPORTANT FACTORS • Renin •Angiotensinogen • Angiotensin I • Angiotensin II • Aldosterone
- 5. RENIN • Released fromkidney • Hydrolyses angiotensinogen
- 6. FACTTORS AFFECTING RENINRELEASE Increased By Decreased By Arterial BP Na+, water retention BP in Glomerular Vessels BP Loss of Na+, water Activation of AT1 receptors(short loop Sympathetic activity negative feedback)
- 7. ANGIOTENSINOGEN • Produced andreleased by liver • Levels increased by corticosteroid, estrogen and thyroid hormone
- 8. ANGIOTENSIN I • Producedin the kidney through action of renin on angiotensinogen • Has no biological activity • Precursor to angiotensin2
- 9. ANGIOTESIN II • Producedby ACE in lungs • Main hormone responsible for increase in blood pressure • Stimulates Na reabsorption and h+ secretion in proximal tubules of kidney
- 11. ANGIOTENSIN III • Has40% activity of angiotensin2 • Has aldosterone producing activity • Causes increase in mean arterial blood pressure
- 12. ACE • Angiotensin convertingenzyme • Acts in the lungs • Catalyses conversion of angiotesin1 to angiotensin2 • Degrades bradykinin to other vasoactive peptides
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- 15. What is beingtested? • Aldosterone is a hormone that plays an important role in maintaining normal sodium and potassium concentrations in blood and in controlling blood volume and blood pressure. Renin is an enzyme that controls aldosterone production. These tests measure the levels of aldosterone and renin in the blood and/or the level of aldosterone in urine. • A variety of conditions can lead to aldosterone overproduction (hyperaldosteronism, usually just called aldosteronism) or underproduction (hypoaldosteronism). Since renin and aldosterone are so closely related, both substances are often tested together to identify the cause of an abnormal aldosterone
- 16. PLASMA RENIN ACTIVITY(PRA) Use Measurementof renin activity is useful in the differential diagnosis of individuals with hypertension. Limitations • Transition to upright posture causes a reduction in renal perfusion pressure and an increase in PRA. PRA levels exhibit a diurnal rhythm, with the highest levels observed in the early morning upon awakening and falling during the day.1 Collecting blood for PRA and aldosterone at midmorning from seated patients following a two to four hour upright posture improves the sensitivity of the aldosterone renin (ARR) for primary aldosteronism. • PRA levels can be increased by dietary salt restriction and suppressed by consumption of a high salt diet. • PRA levels gradually fall as renal function declines with normal aging or with the development of renal impairment due to reduced renin-producing capacity and salt-retenti • A number of drugs can affect the PRA levels.
- 17. Methodology The renin inplasma is allowed to act on the plasma's endogenous substrate, angiotensinogen producing angiotensin I. This is measured by liquid chromatography/mass spectrometry (LC/MS-MS). Age Range (ng/mL/hr) 0 to 11 m 2.000−37.000 1 to 3 y 1.700−11.200 4 to 5 y 1.000−6.500 6 to 10 y 0.500−5.900 11 to 15 y 0.500−3.300 >15 y 0.167−5.380 Reference Interval
- 18. Specimen Requirements Specimen Plasma, frozen Volume 1mL Minimum Volume 0.8 mL (Note: This volume does not allow for repeat testing.) Container Lavender-top (EDTA) tube
- 19. Patient Preparation If inpatientsare physically able, they should be asked to ambulate for 30 minutes before blood is drawn for renin activity Collection Draw blood into an EDTA tube. Keep tube at room temperature. Centrifuge at room temperature. Transfer the plasma into a frozen purple tube with screw cap . Freeze immediately and maintain frozen until tested. It is critical that the plasma be transferred and frozen as quickly as possible to prevent cryoactivation of protein to renin (which results in falsely elevated renin levels). Causes for Rejection Nonfrozen sample received; nonseparated sample received; non-EDTA plasma specimen; gross haemolysis or lipemia.
- 20. ALDESTERONE RENIN RATIO(ARR) Use Screeningtest for primary aldosteronism in higher risk groups of hypertensive patients. Limitations A number of factors can affect the aldosterone: renin ratio and thus lead to false- positive or false-negative results. These include: Factors producing falsely increased ARR (false negative) • Angiotensin-converting enzyme (ACE) inhibitors • Angiotensin II type 1 receptor blockers (ARBs) • Calcium blockers, dihydropyridines (DHPs) • Hypokalaemia • Pregnancy
- 21. Factors producing falselyincreased ARR (false positive) • β-adrenergic blockers • Nonsteroidal anti-inflammatory drugs (NSAIDs) • Renin inhibitors • Potassium loading • Sodium loaded • Advancing age • Renal impairment The ARR should be regarded as a detection test only, and should be repeated if the initial results are inconclusive or difficult to interpret because of suboptimal sampling conditions (e.g., maintenance of some medications listed above). The consensus guideline recommended that patients with a positive ARR should proceed to confirmatory testing by any of four confirmatory tests.
- 22. Methodology Liquid chromatography/tandem massspectrometry (LC/MS-MS) Reference Interval 0−30 ng/dL per ng/mL/hour Container Red-top tube or gel-barrier tube and lavender-top (EDTA) tube Storage Instructions Serum, refrigerated and plasma, frozen
- 23. ANGIOTENSIN II Use Angiotensin IIhas multifaceted effects on aldosterone secretion, vasoconstriction, sodium reabsorption, and fluid volume, all of which serve to raise blood pressure. Several investigators have found that a subgroup of patients with severe chronic heart failure has elevated plasma angiotensin II levels despite long-term ACE inhibitor use. This phenomenon has been referred to as ACE escape or angiotensin II reactivation and has been associated with increased mortality. Limitations The performance characteristics of this product have not been established. Results should not be used as a diagnostic procedure without confirmation of the diagnosis by another medically established diagnostic product or procedure.
- 24. Methodology Radioimmunoassay (RIA) Specimen Requirements Specimen Plasma,frozen Volume 3 mL Minimum Volume 1.5 mL (Note: This volume does not allow for repeat testing.) Container Lavender-top (EDTA) tube Patient Preparation Patient must not have received radioactive substances 24 hours prior to test. Patient should be fasting.