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1. Discuss the RAAS pathway.

The renin-angiotensin-aldosterone system (RAAS) is a signaling pathway responsible for

regulating the body's blood pressure. Stimulated by low blood pressure or certain nerve
impulses (e.g. in stressful situations), the kidneys release an enzyme called renin. This triggers
a signal transduction pathway: renin splits the protein angiotensinogen, producing angiotensin I.
This is converted by another enzyme, the angiotensin-converting enzyme (ACE), into
angiotensin II.

Angiotensin II not only causes blood vessels to narrow (vasoconstriction), it also simultaneously
stimulates the secretion of the water-retaining hormone vasopressin (also called AVP) in the
pituitary gland (hypophysis) as well as the release of adrenaline, noradrenaline and aldosterone
in the adrenal gland. Whereas adrenaline and noradrenaline enhance vasoconstriction,
aldosterone influences the filtration function of the kidneys. The kidneys retain more sodium and
water in the body and excrete more potassium. The vasopressin from the pituitary gland
prevents the excretion of water without affecting the electrolytes sodium and potassium. In this
way, the overall volume of blood in the body is increased: more blood is pumped through
constricted arteries, which increases the pressure exerted on the artery walls – the blood
pressure.

2. Discuss the baroreceptor reflex mechanism in hypertension.

Baroreceptors respond to changes in arterial pressure, by sensing stretch in the vessel wall o
With increased arterial wall pressure → vessel wall stretches → baroreceptors are stimulated →
send increased signals to the medulla → initiates negative feedback loop → inhibits the
sympathetic NS & stimulate parasympathetic NS → vasodilation → decrease peripheral
vascular resistance, reduction in heart rate, decrease in CO → reduction in arterial pressure.

3. What is the use of arterial graft in coronary artery by-pass graft?

Coronary artery bypass grafting (CABG) is a procedure to improve poor blood flow to the heart,
where coronary arteries are narrowed or blocked. CABG uses blood vessels from another part
of the body and connects them to blood vessels above and below the narrowed artery,
bypassing the narrowed or blocked coronary arteries. The blood vessels are usually arteries
from the arm or chest, or veins from the legs.

4. Complications of Myocardial infarction.

 Contractile dysfunction:
 o Left ventricular infarcts
o Acute MI → Severe pump failure or cardiogenic shock
o Right ventricular infarcts
 Right-sided heart failure associated with pooling of blood in the
venous circulation and systemic hypotension.
 Arrhythmias:
o MI → mocardial irritability → fatal arrhythmias
o MI-associated arrhythmias:
 sinus bradycardia, atrial fibrillation, heart block, tachycardia, ventricular
premature contractions, ventricular tachycardia, ventricular fibrillation
 Myocardial rupture: Various forms of cardiac rupture typically occur when there is
transmural necrosis of a ventricle. It incudes:
o Ventricular free wall rupture (MOST COMMON) with fatal hemopericardium
and cardiac tamponade
 Occurs most frequently 2 to 4 days after MI
 Occurs when coagulative necrosis, neutrophilic infiltration, and lysis
of the myocardial connective tissue have appreciably weakened the
infarcted myocardium
o Ventricular septal rupture → acute VSD and L-R shunt
o Papillary muscle rupture (LEAST COMMON) → acute onset of severe mitral
regurgitation
 Ventricular aneurysm:
o True aneurysms (in contrast of false aneurysms) of the ventricular wall are
bounded by myocardium that has become scarred
 Arrhythmias: MIs lead to myocardial irritability and conduction disturbances →
sudden death
 Pericarditis:
o Transmural infarct → A fibrinous or fibrinohemorrhagic pericarditis- develops
about the second or third day as a result of underlying myocardial
inflammation (Dressler syndrome)
 Infarct expansion: weakening of necrotic muscle; disproportionate stretching,
thinning and dilation of infarcted region
o Mural thrombus: Combinations of:
 Local abnormality in contractility → stasis
 Endocardial damage → thrombogenic surface
 Leads to mural thrombosis and thromboembolism
 Papillary muscle dysfunction: result from ischemia → postinfarct mitral
regurgitation
o Papillary muscle fibrosis and shortening or global ventricular dilation →
mitral valve insufficiency

5. Discus the mechanism of hypertension involved in coarctation of aorta.

A pathological constriction or blockage of the aorta at a point beyond the aortic arterial
branches to the head and arms but proximal to the renal arteries is a condition called
coarctation of the aorta. When this occurs, blood flow to the lower body is carried by
multiple, small collateral arteries in the body wall, with much vascular resistance between
the upper aorta and the lower aorta. As a consequence, the arterial pressure in the
upper part of the body may be 40 to 50 percent higher than that in the lower body.

When a constrictor is placed on the aorta above the renal arteries, the blood pressure in both
kidneys at first falls, renin is secreted, angiotensin and aldosterone are formed, and
hypertension occurs in the upper body. The arterial pressure in the lower body at the level of the
kidneys rises approximately to normal, but high pressure persists in the upper body. The
kidneys are no longer isch-emic, and thus secretion of renin and formation of angio-tensin and
aldosterone return to normal. Likewise, in coarctation of the aorta, the arterial pressure in the
lower body is usually almost normal, whereas the pressure in the upper body is far higher than
normal. (REFERENCE: GUYTON)

6. What are the first line anti-hypertensive drugs according to JNC 8 and their
mechanism of action.

DRUGS MOA
THIAZIDE DIURETICS
 Hydrochlorothiazide – Inhibits Na+, Cl- and H2O reabsorption by
PROTOTYPE & most frequently inhibiting the Na+/Cl- cotransporter at the
prescribed DCT
 Chlorothiazide
 Chlorthalidone
 Metolazone
 Indapamide: used in hypertensive
diabetic patients
ACE INHIBITORS
 Captopril In RAAS, Angiotensin II is a potent
 Enalapril vasoconstrictor. By this group of drugs,
 Lisinopril angiotensin II can’t be formed leading to a
 Ramipril decrease in peripheral resistance. This also
 Quinapril induces breakdown of bradykinin which the
 Fosinopril causes vasodilation.

ANGIOTENSIN RECEPTOR BLOCKERS

(ARBs)
 Losartan Blocks the action of AG II at the AT 1
 Candesartan receptors which lowers PVR then low blood
 Valsartan pressure
 Telmisartan
 Irbesartan
 Eprosartan
 Olmesartan
CALCIUM CHANNEL BLOCKERS
 Verapamil Bind α 1 subunit of L-type calcium channel in
 Amlodipin muscle cell membrane located in cardiac
 Nicardipine muscles and vascular smooth muscle leading
 Felodipine to a decrease in intracellular calcium

Can also block cyclic nucleotide PDE

resulting to a decrease cGMP and decreasing
calcium influx, thus there is a dilation of
peripheral arterial cell binding