renin angiotensin system

1. RENIN ANGIOTENSIN ALDOSTERONE
SYSTEM(RAAS)
BY:NAGEEN TALIB

2. CONTENTS
• What is the 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 from kidney
• Hydrolyses angiotensinogen

6. FACTTORS AFFECTING RENIN RELEASE
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 and released by liver
• Levels increased by corticosteroid, estrogen and thyroid hormone

8. ANGIOTENSIN I
• Produced in the kidney through action of renin on angiotensinogen
• Has no biological activity
• Precursor to angiotensin2

9. ANGIOTESIN II
• Produced by 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
• Has 40% activity of angiotensin2
• Has aldosterone producing activity
• Causes increase in mean arterial blood pressure

12. ACE
• Angiotensin converting enzyme
• Acts in the lungs
• Catalyses conversion of angiotesin1 to angiotensin2
• Degrades bradykinin to other vasoactive peptides

14. LABORATORY TESTS

15. What is being tested?
• 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
Measurement of 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 in plasma 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
1 mL
Minimum Volume
0.8 mL (Note: This volume does not allow for repeat testing.)
Container
Lavender-top (EDTA) tube

19. Patient Preparation
If inpatients are 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
Screening test 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 falsely increased 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 mass spectrometry (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 II has 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.