CHAPTER (1)

BLOOD VESSELS

ILOs:

After this lecture student should be able to:

 Describe causes and pathogenesis of hypertension.

 Explain complications of both types of essential hypertension.
 Describe pathological lesions of Malignant essential hypertension in different organs.
 Explain the pathology of atherosclerosis and arteiolosclerosis.
 Mention types of vasculities.
 Describe morphology and effects of Buerger`s disease.
 Mention types and causes and complications of aneurysms.
 Describe morphology of different types of aneurysms.
 Mention causes and effects and complications of varicose veins.

Structure of blood vessels

Vessel walls are formed of three concentric layers: intima, media and adventitia.

Arteries: Arteries are divided into three types

 Large elastic arteries (aorta, aortic arch vessels, iliac and pulmonary arteries). In the
media, elastic fibers alternate with smooth muscle cells. Small arterioles within the
adventitia (vasa vasorum) supply the outer two thirds of the media. The inner third
receive oxygen and nutrients by direct diffusion from the vessel lumen.
 Medium-sized muscular arteries (coronary, renal). Elastic fibers are arranged in an
internal and external elastic lamina.
 Small arteries (< 2mm in diameter), and arterioles lie within the connective tissue of
organs. Their media is mostly formed of smooth muscles. Arterioles regulate the blood
flow resistance.
 Capillaries: Lined by endothelial cells surrounded by pericytes (smooth muscle –like
cells).
 Veins: have larger diameter, wider lumen, thinner wall, with less distinct layers.
HYPERTENSION
Definition: It is the persistent elevation of resting blood pressure above
140/90.
Types of hypertension:
- Etiological classification:
 Primary (essential hypertension)95%: Without obvious cause
 Secondary hypertension: Table(1.1).

- Clinico-pathological classification:
 Benign Hypertension: the rise of blood pressure is gradual and
moderate.
 Malignant hypertension (5%): the rise of blood pressure is rapid.
The blood pressure usually exceeds 200/120.It may start de novo, or
it may appear suddenly in a person with benign hypertension
(accelerated hypertension).

Etiology and pathogenesis of essential hypertension:

The blood pressure is a factor of total peripheral resistance and cardiac
output.
 Impaired renal sodium excretion: leads to increased blood volume
with increase cardiac output.
 Increased vascular resistance due to hypersensitivity of blood
vessels to circulating catecholamines.
 Genetic factors:There is familial clustering of hypertension, may be
linked to specific variation of angiotensinogen and angiotensin II
receptors.
 Environmental factors as stress, obesity, and excess salt intake.
Causes of secondary hypertension:
Renal causes
Renal artery stenosis
Acute and chronic glomerulonephritis
Polycystic kidney
Chronic pyelonephritis.
Endocrine causes
Adrenocortical hyperfunction: primary aldosteronism, Cushing syndrome.
Exogenous corticosteroids
Pheochromocytoma (adrenal medulla tumor secreting catechol amines).
Hyperthyroidism.

Coarctation of aorta (upper half of the body)

Table (1.1) Causes of secondary hypertension

The mechanism of renal hypertension is through excess renin secretionby

the juxtaglomerular cells of the kidney which converts plasma
angiotensinogen to angiotensin I which is then converted to angiotensin II
by angiotensin-converting enzyme. Angiotensin II raises blood pressure by
increasing both peripheral resistance(vasoconstrictor) and blood volume
(stimulation of aldosterone secretion, leading to increase in distal tubular
reabsorption of sodium and increased blood volume.)
Benign hypertension:
Pathological changes
1. Blood vessels:
 Hyaline arteriolosclerosis:
- Generalized changes of small arteries and arterioles
- Homogeneous pink hyaline thickening of the intima and media
with narrowing of the lumen.
- It results due to endothelial injury by hemodynamic stress and
leakage of plasma components into the intima.
 Fibroelastic hyperplasia (elastosis):
- Affects larger arteries
- There is duplication of internal elastic lamina with thickening of the
media.
2. Heart:

 Concentric hypertrophy of the left ventricle

 Acceleration of atherosclerosis, together with increased oxygen
demand due to muscle hypertrophy leads to ischemic heart disease
and angina pectoris.
3. The Kidney: Benign nephrosclerosis(primary contracted
kidney).
Gross:Both kidneys are symmetrically atrophic. The renal surface
shows diffuse fine granularity (resembling leather grain)
 Microscopic: Hyaline arteriolosclerosis of afferent arterioles
(describe), resulting in sclerosis of glomeruli, diffuse tubular atrophy,
and fibrosis. The large arteries show fibroelastic hyperplasia
(describe).
A decrease in GFR and mild degree of proteinuria may be present.
Complications and causes of death in benign hypertension
1. Heart failure
2. Cerebral hemorrhage
3. Chronic renal failure (rare)

Fig (1.1) Diagram of vascular changes in benign hypertension. (Left): Hyalinosis.

(Right): Fibroelastic hyperplasia

Malignant hypertension:
Pathological changes
1. Blood vessels:
 Fibrinoid necrosis of the small arteries and arterioles (granular
eosinophilic material in vessel wall).
 Hyperplastic arteriolosclerosis: onion-skin appearance of
vessels due to hyperplasia of smooth muscle cells and
connective tissue.

2. The kidney:
Gross:The kidney is usually normal in size, or shrunken (in case of
accelerated hypertension). The outer surface shows pin-point
hemorrhages (Flea- bitten kidney)
Microscopic: Arterioles show fibrinoid necrosis. Larger arteries show
hyperplastic arteriolosclerosis.Necrosis may also involve the
glomeruli with microthrombi.
 3. The retina (hypertensive retinopathy):
Retinal hemorrhages and exudates, and papilledoema (edema of
optic disc, leading to blurring of vision)
4. The heart is not markedly hypertrophied due to short duration.
Complications and cause of death
1. Acute renal failure
2. Cerebral hemorrhage
3. Heart failure (rarely)

Figure(1.2) Vascularchanges of malignant hypertension (Left): Fibrinoid necrosis of

glomeruli and afferent arteriole (Right): hyperplastic arteriolosclerosis.

Figure (1.3) The kidney in hypertension (Left): Benign nephrosclerosis: kidney with
leather grain surface (Right): Kidney in malignant hypertension showing pinpoint
hemorrhages(Flea –bitten kidney)
ARTERIOSCLEROSIS
Arteriosclerosis means hardening of the arteries. Three distinct types are
recognized

 Arteriolosclerosis: which affects small arteries and arterioles in

hypertension: Hyaline arteriolosclerosis and hyperplastic
arteriolosclerosis.
 Monckeberg calcific medial sclerosis: Calcific deposits in muscular
arteries, in patients older than 50 years. The lesion do not encroach
on vascular lumen and are of no clinical significance.
 Atherosclerosis: Thickening and hardening of the vessel due to lipid
deposition in the subintimal connective tissue.

ATHEROSCLEROSIS
Definition:

Atherosclerosis is a disease of blood vessels characterized bypatchy

intimal thickening as a result of lipid deposition,covered by fibrous cap.

Risk factors:
 Major risk factors:
1. Hyperlipidemia (hypercholesterolemia):
a) Increased levels of low density lipoproteins(LDL) (bad cholesterol)
which distributes cholesterol to peripheral tissues.
b) Decreased levels of high density lipoproteins(HDL) (good
cholesterol), which mobilizes cholesterol from developing plaques
and transport to the liver to be excreted in bile.
Increased LDL may be hereditary or related to diet (increase intake of
animal fat or trans fats from artificial hydrogenation of oils). Exercise and
omega 3 fatty acids in fish oil increases HDL levels.
2. Hypertension. Both systolic and diastolic BP are important. The high
pressure causes endothelial injury.
3. Diabetes mellitus causes hypercholesterolemia.
4. Smoking.

 Constitutional risk factors:

1. Advanced age:Atherosclerosis becomes clinically apparent at 40-60
years.
 2. Gender. Women in child bearing age are relatively protected (by
estrogen) but the incidence increases after the menopause.
3. Genetics. Family history is an important independent risk factor.
 Hereditary hypercholesterolemia accounts for a small
percentage of cases.
 Familial risk is due to the fact that the major risk factor
(diabetes and hypertension) are polygenic in nature
(controlled by multiple genes).
4. Lack of exercise and living a competitive stressful life style.

Pathogenesis :
Response to injury hypothesis (interplay of endothelial injury and
inflammation).
a) Hyperlipidemia, hypertension, smoking and hemodynamic forces.
causeendothelial injury(atheromatous plaques tend to occur at
ostia of vessels, at branching points of vessels where turbulence is
high).
The endothelial injury leads toincreased permeability to LDL, which
accumulates in the intima.

b) Platelets adhere to the endothelium, also monocytes adhere to the

endothelium and migrate into the intima and transform to
macrophages.

c) Endothelial cells as well as monocytes release oxygenfree radicals

which cause oxidation of soluble LDL to insoluble oxidized LDL.
Insoluble LDL and cholesterol crystals are taken up by macrophages
which change to foam cells.

d) Under the effect of platelet derived growth factors, smooth muscle

cells from the media migrate to the intima and proliferate. They
secrete extracellular matrix (ECM) namely collagen.

e) T cells are recruited to the intima, are activated and produce

inflammatory cytokines which stimulate macrophages, endothelial
cells and smooth muscle cells (the exact antigen and cause of Tcell
activation is not clear).
 Figure (1.1) Pathogenesis of atherosclerosis.

Morphology:

1- Fatty Streaks.
 Fatty streaks are the earliest lesions in atherosclerosis as early
as age of 10.
 They are composed of lipid-filled foamy macrophages.
 They are seen grossly as elongated streaks 1 cm or more in
length.
 These lesions are not significantly raised and do not cause any
flow disturbance.
2- Atheromatous Plaque.
 These are areas of intimal thickening and lipid accumulation.
 White to yellow raised lesions 0.3-1.5 cm in diameter, but can
coalesce to form larger masses. Superadded thrombosis givethe
lesions a red-brown color.
 Lesions affect only part of the circumference of vessels so on
cross section the lesion appears eccentric.

Sites:

- In descending order, the most extensively involved vessels are the

infrarenal abdominal aorta, the coronary arteries, the poplitealarteries,
the internal carotid arteries, and the vessels of the circle of Willis.
- Vessels of the upper extremities are usually spared, as are the
mesenteric and renal arteries, except at their ostia.
 - Nevertheless, in an individual case, the severity of atherosclerosis in
one artery does not predict its severity in another.

Microscopic picture:

- Atheromatous plaques consist of a central lipid core covered by a

fibrous cap of smooth muscle cells and collagen.
- The central core contains lipids, (cholesterol, necrotic debris, lipid
laden macrophages (foam cells, fibrin and other plasma
proteins).The cholesterol appears as needle shaped clefts (because
the cholesterol dissolves during slide preparation).
- The shoulder region, where the fibrous cap meets the vessel wall is
more cellular and contains macrophages, T cells and smooth muscle
cells. Later it shows neovascularization (proliferated small blood
vessels).
- Secondary changes include ulceration, thrombosis and calcification.
- The media opposite the plaques are thin due to smooth muscle
atrophy and loss.

Fig (1.4) Pathology of atherosclerosis: A. Fatty streaks. B. Atheromatous plaques.(Lower

Left) Atheroma, C lipid core, F fibrous cap. (Lower right) Early lesions: foam cells
Effect and Complications:

 Artery stenosis (in medium sized arteries as coronary): leading

to diminished tissue perfusion e.g. cardiac ischemia and angina
pectoris.
 Hemorrhage into a plaque. Rupture of the overlying fibrous cap,
or of the thin-walled vessels in the areas of neovascularization,
increase the size of the plaque and it may rupture.
 Atheroembolism. Plaque rupture can discharge atherosclerotic
debris into the bloodstream, producing microemboli.
 Aneurysm formation. Pressure atrophy of the media resulting in
aneurysmal dilation and potential rupture.

VASCULITIS
Definition: Vessel wall inflammation

1. Infectious vasculitis:
 Bacterial or fungal infections of arterial wall (may lead to mycotic
aneurysm.
 Syphilitic aortitis.

2. Non-infectious vasculitis
 Hypersensitivity vasculitis

These are immune mediated diseases, commonly by immune complex

deposition in vessel wall. These are multisystem disordersbut affecting
mainly highly vascular tissues as the skin, glomerulus, lung and GIT. E.g.
polyarteritisnodosa, systemic lupus erythematosus, Henoch-
schoenleinpurpura.

 Buerger disease (thrombangiitisobliterans) related to smoking.

Polyarteritisnodosa (PAN):
- An immune mediated systemic disease affecting males more than
female, affecting small & medium sized arteries.

- One third of patients have chronic hepatitis B infection, which lead to

formation of immune complex deposits containing B antigens in the vessel
wall.
Morphology

- Segmentaltransmuralfibrinoid necrosis of arterial wall, surrounded by

an acute inflammatory reaction.
- Lesions usually affect only part of the vessel circumference.

Complications:
1- Thrombosis with vascular occlusion or emboli resulting in infarctions.
2- Aneurysm due to segmental inflammatory weakening of the arterial
wall. Occurs especially in coronaries, cerebral or mesenteric
arteries.
3- Rupture resulting in tissue hemorrhages e.g. melena.

Thrombangiitisobliterans (Buerger’sdisease):
- Definition: A segmental, inflammatory disease that most commonly
affects the tibial and radial arteries, adjacent veins, and nerves
(neurovascular bundle).
- It occurs almost exclusively in heavy smokers.

Morphology:
- There is a sharply segmental acute transmural inflammation with
microabscess formation. The inflammationoften extends to adjacent veins
and nerves. Thrombosis, organization and recanalization often occurs.

Clinical picture:
It affects mainly the legs, maybe the hands, with severe pain and
progressive ischemic changes which may end in gangrene.

ANEURYSMS
Definition: Localized permanent arterial wall dilatation.

Pathogenesis: Weakness of the vessel wall due to one of the following

causes:

1. Congenital absence of muscle wall and replacement by fibrous

tissue.
2. Loss of smooth muscle cells as in
 Atherosclerosis: Thickened intima may cause ischemia of the
media due to decreased diffusion of nutrients. Also thickened
vasa vasorum by hypertension may cause ischemia of the
 outer media. Common site of atherosclerotic aneurysm is
abdominal aorta.
 Syphliticaortitis: Inflammation of the aorta in tertiary syphilis
with endarteritis obliterans of vasa vasorum causing ischemia
of the media, with loss of muscle cells. Syphilitic aneurysm
occurs in ascending aorta.
3. Weakening of the arterial wall secondary to infection resulting in the
so- called mycotic aneurysm. Mycotic aneurysms result from
 Embolization of infected embolus as a complication of infective
endocarditis.Commonest site is in the cerebral arteries.
 As an extension of an adjacent suppurative process.
4. Vasculitis. Immune mediated inflammation of arteries weaken the
vessel wall leading to small arterial dilatation as in
polyarteritisnodosa.

Classification of aneurysms

 Aneurysms may be classified by shape into:

 Saccularaneurysm areoutpouchimgs from 5 to 20 cm, from one
side of arterial wall, often with a contained thrombus.
 Fusiform aneurysms are circumferential Dilatations up to 20 cm
in diameter. These commonly involve aortic arch, the abdominal
aorta and iliac arteries.

NB. False aneurysms (pseudoaneurysm) arise due to a penetrating injury

in arterial wall leading to the formation of an extravascular hematoma
which becomes surrounded by adventitial fibrosis, forming a sac
communicating with the vascular lumen (pulsating hematoma). Examples
of penetrating injuries:bullets or shrapnels, femoral artery puncture during
arteriography or percutaneous angioplasty.
 Figure (1.5) Types of aneurysm

 Aneurysms may be classified according to etiology:

1. Congenital aneurysm: Small berry aneurysm of cerebral arteries at
the branching of the circle of Willis. Rupture leads to subarachnoid
hemorrhage.
2. Atherosclerotic aneurysm in abdominal aorta, iliac arteries. They
are saccular or fusiform in shape.
3. Syphilitic aneurysm affects ascending part or arch of aorta.
Saccular in appearance.
4. Mycotic aneurysm: cerebral, coronary,mesenteric.
5. Polyarteritisnodosa

Complications of aneurysms:

1. Rupture causing hemorrhage.

2. Mural thrombus formation with possible occlusion of ostia of vessels
branching off the aorta e.g. renal or mesenteric artery. Embolism
may occur.
3. Pressure on surrounding structures (e.g. vertebrae in cases of aortic
aneurysm.

Acute aortic dissection (dissecting aortic aneurysm):

Blood is forced through a tear in the intima of the aorta and tracks down
the aorta splitting the media in two, forming a blood-filled channel within
the aortic wall.
Causes:

1- Hypertension is the main cause, with cases presenting at age 40-60.

2- Marfan syndrome: congenital absence of fibrillin, a glycoprotein
closely associated with elastic fibers.Thisoccurs in younger patients.

Figure (1.6) Aortic dissection.

Morphology

1. The tear commonly startin the aorta within 10 cm of aortic valve. The
dissection spreads distally or towards the heart.
2. Microscopically: cystic medial necrosis may be seen especially in
cases associated with Marfan syndrome. Medial necrosis is
characterized by mucoid degeneration and elastic fiber
fragmentation.
3. External rupture causes massive hemorrhage or cardiac temponade
if it occurs in the pericardial cavity.

Clinical picture:

Sudden onset of severe pain starting in the chest, radiating to the back
between the scapulae as the dissection progresses. It is associated
with high mortality and treatment is surgical.
VARICOSE VEINS
Definition:
Varicose veins are abnormally dilated, tortuous veins, produced by
prolonged, increased intraluminal pressure leading to vessel dilation and
incompetence of the venous valves.
13Etiology
- Familial predisposition.
- Risk factors include occupations with prolonged standing, obesity and
pregnancy.
Complications:
1. Pain, congestion, edema and stasis dermatitis.
2. Chronic varicose ulcer (poor wound healing and superadded
infection).
 Varicose veins of the esophagus (esophageal varices):
Esophageal varices complicate portal hypertension of any cause, .cirrhosis
and bilharzialperiportal fibrosis. This leads to the opening of porto-systemic
shunts and increased blood flow to the veins in lower esophagus.
 Hemorrhoids:
- Varicose dilatation of veins at the anorectal junction from prolonged
pelvic venous congestion associated with pregnancy and straining at
defecation.
- They are a source of bleeding per rectum, liable to thrombosis and
painful ulceration.
FORMATIVE ASSESSMENT
SAQ:

List risk factors for atherosclerosis

MCQ

1. The most common site of atherosclerotic aneurysm is:

a) Ascending aorta
b) Abdominal aorta
c) Femoral artery
d) Carotid artery.
 2. Which one of the following is not involved in the etiology of secondary
hypertension
a) Atherosclerosis
b) Renal artery stenosis
c) Chronic glomerulonephritis
d) Phaeochromocytoma
3. The most common cause of death in cases of malignant hypertension.
a) Chronic renal failure
b) Acute renal failure
c) Heart failure
d) Cerebral thrombosis

References:

http://www.uaz.edu.mx/histo/pathology/ed/ch_1/c1_s33.htm

http://www.medrx-education.com/cardiology-review/arteriolosclerosis

https://image.slidesharecdn.com/atn-csbrp-151030053520-lva1-
app6892/95/atn-csbrp-28-638.jpg?cb=1446183421

http://peir.path.uab.edu/library/_data/i/upload/2013/08/01/20130801095945
-3dff127b-me.jpg

https://upload.wikimedia.org/wikipedia/commons/thumb/f/f1/Atherosclerosi
s%2C_aorta%2C_gross_pathology_PHIL_846_lores.jpg/230px-
Atherosclerosis%2C_aorta%2C_gross_pathology_PHIL_846_lores.jpg

https://www.pharmacology2000.com/Cardio/Cardio_risk/fatty_streaks1.jpg

http://slideplayer.com/slide/5795119/19/images/29/Microscopic+appearanc
e+of+atherosclerotic+lesions.jpg