Hypertension B.Pharmacy 2nd Semester 2023 (2022-2023) Previous Year's Question Papers/Notes Download - HK Technical PGIMS

HYPERTENSION
The blood vessels are closed circuits for the transport of blood from the left heart to
the metabolising cells, and then back to the right heart.
The blood containing oxygen, nutrients and metabolites is routed through arteries,
arterioles, capillaries, venules and veins. These blood vessels differ from each other
in their structure and function.
ARTERIES
NORMAL STRUCTURE
Depending upon the calibre and certain histologic features, arteries are divided into 3
types:
1. Large (elastic) arteries,
2. Medium-sized (muscular) arteries and
3. The smallest arterioles.
Histologically, all the arteries of the body have 3 layers in their walls:
1. The tunica intima,
2. The tunica media and the
3. Tunica adventitia.
These layers progressively decrease with diminution in the size of the vessels.
Tunica intima
 Inner coat of the artery.
 Composed of the
o Lining endothelium
 Flattened cells adjacent to the flowing blood.
 Maintain vascular function.
o Subendothelial connective tissue
 Consists of loose meshwork of connective tissue that includes
myointimal cells, collagen, proteoglycans, elastin and matrix
glycoproteins.
o Bounded externally by internal elastic lamina.
Tunica media
 Middle coat of the arterial wall,
 Bounded internally by internal elastic lamina and externally by external elastic
lamina.
 This layer is the thickest and consists mainly of smooth muscle cells and
elastic fibres.
 The external elastic lamina consisting of condensed elastic tissue is less well
defined than the internal elastic lamina.
Tunica adventitia.  The outer coat of arteries is the tunica adventitia.  It consists of loose mesh of connective tissue and some elastic fibres that
merge with the adjacent tissues.  This layer is rich in lymphatics and autonomic nerve fibres.
There are 3 main kinds of blood vessels – arteries, veins and capillaries. Arteries carry
blood away from the heart. They divide again and again, and eventually form very tiny
vessels called capillaries. The capillaries gradually join up with one another to form
large vessels called veins. Veins carry blood towards the heart
Hypertensive Vascular Disease
Systemic and local tissue blood pressures must be maintained within a narrow range
to prevent untoward consequences.
Low blood pressure (hypotension) results in inadequate organ perfusion and can
lead to tissue dysfunction or death.
Conversely, high blood pressure (hypertension) can cause end-organ damage and is
one of the major risk factors for atherosclerosis.

Blood Pressure Regulation
Blood pressure is a function of cardiac output and
peripheral vascular resistance, both of which are inflenced by multiple genetic
and environmental factors
Cardiac output is a function of stroke volume and heart rate. The most important
determinant of stroke volume is the filing pressure, which is regulated through sodium
homeostasis and its effect on blood volume. Heart rate and myocardial contractility (a
second factor affecting stroke volume) are both regulated by the αand β-adrenergic
systems, which also have important effects on vascular tone.
Peripheral resistance is regulated predominantly at the level of the arterioles by
neural and hormonal inputs. Vascular tone reflcts a balance between vasoconstrictors
(including angiotensin II, catecholamines, and endothelin) and vasodilators (including
kinins, prostaglandins, and nitric oxide). Resistance vessels also exhibit
autoregulation, whereby increased blood flw induces vasoconstriction to protect
tissues against hyperperfusion. Finally, blood pressure is fie-tuned by
tissue pH and hypoxia to accommodate local metabolic demands
Factors released from the kidneys, adrenals, and myocardium interact to
inflence vascular tone and to regulate blood volume by adjusting sodium
balance.
The kidneys fiter 170 L of plasma containing 23 moles of salt daily. Thus, with a typical
daily diet containing 100 mEq of sodium, 99.5% of the fitered salt must be reabsorbed
to maintain total body sodium levels. About 98% of the fitered sodium is reabsorbed
by constitutively active sodium transporters. The small amount of remaining sodium is
subject to resorption by the epithelial sodium channel (ENaC), which is tightly
regulated by the reninangiotensin system; it is this pathway that determines net
sodium balance.
The kidneys and heart contain cells that sense changes in blood pressure or volume.
In response, these cells release circulating effectors that act in concert to maintain
normal blood pressure. Kidneys inflence peripheral resistance and sodium
excretion/retention primarily through the renin-angiotensin system.
• Renin is a proteolytic enzyme produced by renal juxtaglomerular cells, myoepithelial
cells that surround the glomerular afferent arterioles. Renin is released in response to
low blood pressure in afferent arterioles, elevated levels of circulating catecholamines,
or low sodium levels in the distal convoluted renal tubules. The latter occurs when the
glomerular fitration rate falls (e.g., when the cardiac output is low), leading to increased
sodium resorption by the proximal tubules.
• Renin cleaves plasma angiotensinogen to angiotensin I, which in turn is converted
to angiotensin II by angiotensin-converting enzyme (ACE), mainly a product of
vascular endothelium. Angiotensin II raises blood pressure by (1) inducing vascular
contraction, (2) stimulating aldosterone secretion by the adrenal gland, and
(3) increasing tubular sodium resorption. Adrenal aldosterone increases blood
pressure by increasing sodium resorption (and thus water) in the distal convoluted
tubule, which increases blood volume.
The kidney also produces a variety of vascular relaxing substances (including
prostaglandins and NO) that presumably counterbalance the vasopressor effects of
angiotensin.
Myocardial natriuretic peptides are released from atrial and ventricular myocardium in
response to volume expansion; these inhibit sodium resorption in the distal renal
tubules, thus leading to sodium excretion and diuresis. They also induce systemic
vasodilation.

Pathogenesis of Hypertension
Hypertension is a disorder with multiple genetic and environmental contributions. As
already noted, the vast majority (90% to 95%) of hypertension is idiopathic. Even without knowing the specific lesions, it is reasonable to suppose that multiple
small changes in renal sodium homeostasis and/or vessel wall tone or structure act
in combination to cause essential hypertension.
Most other causes fall under the general rubric of renal disease, including
renovascular hypertension (due to renal artery occlusion). Infrequently, hypertension
has an underlying endocrine basis.
Pathogenesis of Secondary Hypertension. In many secondary forms of
hypertension, the underlying pathways are reasonably well understood:
• In renovascular hypertension, renal artery stenosis causes decreased glomerular
flow and pressure in the afferent arteriole of the glomerulus. This induces renin
secretion, which, as already discussed, increases vascular tone and blood volume
via the angiotensin-aldosterone pathway.
• Single-gene disorders cause severe but rare forms of hypertension:  Gene defects affecting enzymes involved in aldosterone metabolism(e.g., aldosterone synthase, 11 β-hydroxylase, 17α-hydroxylase). These lead
to an increase in secretion of aldosterone, increased salt and water
resorption, plasma volume expansion and, ultimately, hypertension. Primary
hyperaldosteronism is one of the most common causes of secondary
hypertension  Mutations affecting proteins that inflence sodium reabsorption. For
example, the moderately severe form of salt-sensitive hypertension, called
Liddle syndrome, is caused by gain-of-function mutations in an epithelial Na+
channel protein that increase distal tubular reabsorption of sodium in
response to aldosterone
Mechanisms of Essential Hypertension
• Genetic factors inflence blood pressure regulation, as shown by comparisons of
monozygotic and dizygotic twins, and genetically related versus adopted children.
Moreover, as noted earlier, several single-gene disorders cause relatively rare forms
of hypertension (and hypotension) by altering net sodium reabsorption in
the kidney. It is also suspected (but not yet proven) that variations in blood pressure
may result from the cumulative effects of polymorphisms in several genes that affect
blood pressure; for example, sequence variants in both the angiotensinogen and the
angiotensin receptor genes have been associated with hypertension in some studies.
• Reduced renal sodium excretion in the presence of normal arterial pressure
may be a key initiating event in essential hypertension and, indeed, a fial common
pathway for the pathogenesis of hypertension. Decreased sodium excretion may lead
sequentially to an increase in fluid volume, increased cardiac output, and peripheral
vasoconstriction, thereby elevating blood pressure. At the higher blood pressure,
enough additional sodium is excreted by the kidneys to equal intake and prevent
further flid retention. Thus, a new steady state of sodium balance is achieved
(“resetting of pressure natriuresis”), but at the expense of an increase in blood
pressure.
• Vasoconstrictive inflences, such as factors that induce vasoconstriction or stimuli
that cause structural changes in the vessel wall, can lead to an increase in peripheral
resistance and may also play a role in essential hypertension.
• Environmental factors, such as stress, obesity, smoking, physical inactivity, and
heavy salt consumption are all implicated in hypertension. Indeed, the evidence linking
dietary sodium intake with the prevalence of hypertension in different populations is
particularly impressive.
Cardiac output and peripheral resistance are the two determinants of arterial
pressure.
[6] Cardiac output is determined by stroke volume and heart rate; stroke
volume is related to myocardial contractility and to the size of the vascular
compartment. Peripheral resistance is determined by functional and anatomic
changes in small arteries and arterioles.