disorders of vein

1. COMMON DISORDERS OF
ARTERIES AND VEINS

2. HYPERTENSIVE VASCULAR
DISEASE

3. Blood pressure regulation
Blood pressure is determined by cardiac out put
and peripheral vascular resistance
Vascular resistance is regulated at the level of the
arterioles, influenced by neural (adrenergic) and
hormonal (angiotensin) inputs
Cardiac output is determined by heart rate and
stroke volume
Blood volume in turn is regulated mainly by renal
sodium excretion or resorption

4. Cont’d
Kidneys influence peripheral resistance and
sodium excretion/retention primarily through
renin-angiotensin-aldosterone system
Renin, a major regulator of blood pressure, is
secreted by the kidneys in response to
decreased blood pressure

7. Hypertension(HTN)
 Cutoffs in diagnosing hypertension in clinical practice
sustained diastolic pressures >90 mm Hg, and/or
sustained systolic pressures >140 mm Hg
 Malignant hypertension: A small percentage of HTN
patients (5%) present with a rapidly rising blood
pressure
systolic pressures > 200 mm Hg or diastolic pressures >
120 mm Hg
 associated with renal failure and retinal
hemorrhages and exudates
 more often is superimposed on preexisting benign
hypertension

8. Types of hypertension
1- Essential
hypertension: most
cases (95%) are
idiopathic.
2- Secondary
hypertension: due to
renal disease, or renal
artery narrowing
(renovascular
hypertension), and
adrenal disorders

9. Pathogenesis of essential HTN
Reduced renal sodium excretion: most
etiologic factor
Decreased Na+ excretion —› increase fluid volume
—› increase blood volume —› HTN
Increased vascular resistance
Genetic factors
HTN has been linked to specific angiotensinogen
polymorphisms and angiotensin II receptor
variants; polymorphisms of the renin-angiotensin
system.

10. Cont’d
Environmental factors
• stress
• obesity
• Smoking
• physical inactivity
• high levels of salt consumption,

11. Complications of HTN
• stroke (CVD)
• multi-infarct dementia
• atherosclerotic coronary heart disease
• cardiac hypertrophy and heart failure
(hypertensive heart disease)
• aortic dissection
• renal failure

13. Morphology
HTN is associated with arteriolosclerosis
(small arterial disease)
Large Blood Vessels (Macroangiopathy)
–Atherosclerosis, HT is a major risk factor in
AS.
Two forms of small blood vessel disease are
hypertension-related:
1- hyaline arteriolosclerosis
2- hyperplastic arteriolosclerosis

14. Hyaline arteriolosclerosis
 Associated with benign
hypertension.
 Marked by homogeneous, pink
hyaline thickening of the
arteriolar walls, and luminal
narrowing.
 Results from:
 leakage of plasma components
across injured endothelial cells
into vessel walls
 increased ECM production by
smooth muscle cells in response
to chronic hemodynamic stress
 Complications:
- Most significant in the
kidneys
nephrosclerosis
(glomerular scarring).
 Other causes of hyaline
arteriolosclerosis (in
absence of HTN):
1- elderly patients
(normo-tensive)
2- diabetis mellitus

15. Cont’d

16. Hyperplastic arteriolosclerosis
Is more typical of severe hypertension.
"onionskin," concentric, laminated thickening of
arteriolar walls and luminal narrowing.
The laminations consist of smooth muscle cells
and thickened, reduplicated basement
membrane.
 In malignant hypertension these changes are
accompanied by fibrinoid deposits and vessel
wall necrosis (necrotizing arteriolitis), which are
particularly prominent in the kidney

17. Cont’d

18. VASCULAR WALL RESPONSE
TO INJURY
Injury to the vessel wall (particular to Ecs)—is
the fundamental basis for the vast majority
of vascular disorders
The integrated function of ECs—and the
underlying SMCs—is critical for the
vasculature to respond to various stimuli (
adaptive or leads to pathologic lesion)

19. Intimal Thickening
Is stereotypical Response to Vascular Injury
Vascular injury leading to EC loss or dysfunction
stimulates :
– SMC growth,
– ECM synthesis
– thickening of the vascular wall
Migration of SMCs or SMC precursor cells into the
intima then proliferate and synthesize ECM.
Forming a neointima that typically is covered by
an intact EC layer

20. Cont’d
The phenotype of neointimal SMCs is distinct
from medial SMCs
The migratory, proliferative, and synthetic
activities of the intimal SMCs are regulated by
growth factors and cytokines produced by
platelets, ECs, and macrophages
persistent or recurrent insults, further
thickening can occur that leads to the stenosis
of small- and medium sized blood vessels

22. Diseases of arteries

23. ARTERIOSCLEROSIS
Is hardening of the arteries”(arterial wall
thickening and loss of elasticity).
There are four distinct types
1. Arteriosclerosis:
Hyaline & hyperplastic thickening of small
arteries & arterioles cause luminal narrowing &
ischemia.
2. Monckeberg medial sclerosis:-
Characterized by formation of:-
- Calcific deposits (Irregular medial plate)
- In medium-sized muscular arteries.
- In persons > 50 years

24. Cont’d
3.Fibromuscular intimal hyperplasia
is a non-atherosclerotic process that occurs in
muscular arteries larger than arterioles
predominantly an SMC- and ECM-rich lesion
driven by inflammation or mechanical injury
4. Atherosclerosis:
Characterized by formation of:-
- Intimal fibrous plaques
- Have central core rich in lipid=fibro-fatty
plaques

25. ATHEROSCLEROSIS
 Atherosclerosis is characterized by intimal lesions
called atheromas (or atheromatous or atherosclerotic
plaques) that impinge on the vascular lumen and can
rupture to cause sudden occlusion
 Commonest.
- Contributes to high morbidity & mortality
(> half of all death).
 It primarily affects:-
- Large Elastic arteries:- (aorta, carotid, iliac arteries).
- Large & medium muscular arteries(coronary &
popliteal arteries).

26.  Atheromatous
plaques are
raised lesions
composed of
soft friable
(grumous) lipid
cores (mainly
cholesterol and
cholesterol
esters, with
necrotic debris)
covered by
fibrous cap

27. Atherosclerosis Risk Factors

28. Hyperlipidemia
Is a major risk factor for atherosclerosis, more
specifically hypercholesterolemia
Total serum cholesterol include:-
 LDL( Bad cholestrol)
HDL( Good cholestrol)
Cholesterol
TG
The various classes of blood lipids are transported
as lipoproteins complexed to specific apoproteins

29. Dyslipoproteinemias
Causes:-
1. Genetic mutations:- Involving apolipoproteins
genes.
2. Other underlying disorder:-
• Like nephrotic syndrome, alcoholism,
diabetes mellitus, hypothyreoidism.
 Types of lipoprotein abnormalities:-
1. Increased LDL / cholesterol level.
2. Decreased HDL / cholesterol level.
3. Increase level of an abnormal lipoprotein
Lp(a).

30. Other Risk Factors Of
arterial Diseases
Hypertension:
– Strong risk factor > hypercholesterolemia after age
45y.
- BP > 169/90 mm Hg have 5X > risk of IHD
than those with BP of 140/90 mm Hg.
 Smoking:
– One or more packs of cigarettes /day for several years,
increases the death rate from IHD twice.
 Diabetes mellitus:
 DM induces hypercholesterolemia atherosclerosis.
The incidence of MI is 2X, stroke is 4X greater, and the
incidence of lower extremities gangrene is 100X.

31. Cont’d
Inflammation:
 pro-inflammatory state is associated with the
development of atherosclerosis
measures of systemic inflammation have been used
in risk stratification
C-reactive protein (CRP) is systemic marker of
inflammation and produced in liver
CRP levels independently predict the risk for
myocardial infarction, stroke, peripheral arterial
disease, and sudden cardiac death, even among
apparently healthy individuals

32. Cont’d
Elevated Plasma Homocysteine:
Increased serum homocysteine levels —›
Artery disease (IHD, peripheral vascular disease,
stroke, & DVT).
Elevated levels of procoagulants
are potent predictors of risk for major
cardiovascular events including myocardial
infarction and stroke

33. Pathogenesis of atherosclerosis
• “response to injury” hypothesis
• This model views atherosclerosis as a chronic inflammatory
and healing response of the arterial wall to endothelial
injury
• Lesion progression occurs through interaction of
modified lipoproteins, macrophages, and T lymphocytes
with ECs and SMCs of the arterial wall
1) Endothelial Injury
• the three most important causes of endothelial
dysfunction are hemodynamic disturbances,
hypercholesterolemia, and inflammation.

34. 2. Deposits of Lipoproteins (LDL &
cholesterol crystals) into the vessel
wall.
3. Oxidation of these lipoproteins.
4. Adhesion of platelets to focal areas of
adherent leukocytes
5. Adhesion of monocytes to the
endothelium.
6. Migration of monocytes into the
intima.

35. Cont’d
7. Transforamation of monocytes into macrophages &
foam cells.
8.Release of factors from activated platelets &
Macrophage
9. Migration of smooth muscle from media into intima.
10. Proliferation of smooth muscle in the intima &
elaboration of extracellular matrix.
11. Accumulation of collagen & proteoglycans.
12.Enhanced accumulation of lipids within
macrophages, smooth muscle and extracellularly

37. The mechanisms of dyslipidemia to
cause atherogenesis
 Increasing local oxygen free radical
production ( EC dysfunction)
Lipoproteins accumulate within the intima
and generate oxidized LDL and cholesterol
crystals.
Oxidized LDL stimulates the local release of
growth factors, cytokines, and chemokines,
increasing monocyte recruitment
LDL also is cytotoxic to ECs and SMC

38. Inflammation
Monocytes differentiate into macrophages
and avidly engulf lipoproteins
Activated macrophages also produce toxic
oxygen species that drive LDL oxidation and
that stimulate SMC proliferation.
Activated T cells in the growing intimal lesions
elaborate inflammatory cytokines (e.g., IFN-γ),
which stimulate macrophages, ECs, and SMCs

39. SMC Proliferation and Matrix
Synthesis
Intimal SMC proliferation and ECM deposition
lead to conversion of the earliest lesion, a
fatty streak into a mature atheroma,
It contributing to the progressive growth of
atherosclerotic lesions

40. Morphology
The development of atherosclerosis tends to
follow a series of morphologic changes
1. Fatty Streaks:
Minute yellow, flat macules that coalesce into
elongated lesions, 1 cm or more in length
composed of lipid-filled foamy macrophages but
are only minimally raised
do not cause any significant flow disturbance
Fatty streaks can appear in infants and older
children

41. Cont’d

42. 2. Atherosclerotic Plaque
 The key features of these lesions are intimal thickening
and lipid accumulation
 White to yellow raised lesions and range from 0.3 to
1.5 cm in diameter
 Atherosclerosis involves the infrarenal abdominal
aorta, the coronary arteries, the popliteal arteries, the
internal carotid arteries, and the vessels of the circle of
Willis
 Atherosclerotic plaques have three principal
components:
(1) cells, including SMCs, macrophages, and T cells

43. Cont’d
(2)ECM, including collagen, elastic fibers, and
proteoglycans;
(3) Intracellular and extracellular lipid
 Plaques have a superficial fibrous cap composed of SMCs
and relatively dense collagen.
 Cap meets the vessel wall (the “shoulder”) is a more
cellular area containing macrophages, T cells, and SMCs
 Deep to the fibrous cap is a necrotic core, containing lipid
(primarily cholesterol and cholesterol esters), necrotic
debris, lipidladen macrophages and foam cells.
 The periphery of the lesions shows neovascularization
(proliferating small blood vessels
 Atheromas also often undergo calcification

45. Cont’d

46. Acute Plaque Change
Plaque erosion or rupture typically triggers
thrombosis,leading to partial or complete
vascular obstruction and often tissue infarction
1. Rupture/fissuring, exposing highly
thrombogenic plaque constituents
2. Erosion/ulceration, exposing the thrombogenic
subendothelial basement membrane to blood
3. Hemorrhage into the atheroma, expanding its
volume

47. Cont’d

48. Symptom of atherosclerotic
disease
Related to arteries supplying the:-
- Heart. = MI
- Brain. = Stroke
- Kidneys.= Kidney failure.
- Lower extremities = gangrene.
- Small intestine = gangrene.

49. Cont’d

50. Consequences of Atherosclerosis
Aortic aneurysms.
Gangrene of the legs.
Gangrene of intestine (Mesenteric
occlusions)
Ischemic encephalopathy.
Chronic IHD.
 Sudden death

52. ANEURYSMS AND DISSECTIONS

53. Aneurysm
Are congenital or acquired dilations of blood
vessels or the heart
True” aneurysms: involve all three layers of the
artery (intima, media, and adventitia)
False aneurysm (pseudoaneurysm): The wall is
ruptured, creating a collection of blood
(hematoma) bounded externally by adherent
extravascular tissues.
Saccular aneurysms : discrete outpouchings
Fusiform aneurysms: circumferential dilations

54. Cont’d

55. Pathogenesis
1. Inadequate or abnormal connective tissue
synthesis: mutations in TGF-β receptors,
Marfan syndrome, Ehlers-Danlos syndrome
2. Excessive connective tissue degradation:
Increased matrix metalloprotease expression
3. Loss of SMCs or change in the SMC synthetic
phenotype

56. Cont’d
The two most important predisposing conditions
for aortic aneurysms are atherosclerosis and
hypertension
Atherosclerosis is the dominant factor in
abdominal aortic aneurysms, while hypertension
is associated with ascending aortic aneurysms
Other causes
trauma
Vasculitis
congenital defects
infections

57. Cont’d
Mycotic aneurysms may result from
(1) Embolization of a septic embolus, usually as
a complication of infective endocarditis;
(2) Extension of an adjacent suppurative
process;
(3)Direct infection of an arterial wall by
circulating organisms.

58. Abdominal Aortic Aneurysm
 occurring as a consequence of atherosclerosis
 Form most commonly in the abdominal aorta and common
iliac arteries
 Occur more frequently in men and in smokers
 Morphology:
Occur renal arteries and the aortic bifurcation;
They can be saccular or fusiform
Contains bland, laminated, poorly organized mural
thrombus,
 Inflammatory AAAs are a distinct subtype characterized by
dense periaortic fibrosis containing abundant
lymphoplasmacytic inflammation with many macrophages
and giant cells

60. Clinical Consequences
 Obstruction of a vessel branching off the aorta
resulting in ischemia of the kidneys, legs, spinal cord,
or gastrointestinal tract
 Embolism of atheromatous material (e.g., cholesterol
crystals) or mural thrombus
 Impingement on adjacent structures
 An abdominal mass (often palpably pulsating)
 Rupture into the peritoneal cavity or retroperitoneal
tissues

61. VASCULITIS
• is a general term for vessel wall inflammation
with protean manifestations depending on the vascular bed
affected
• Besides this findings, the clinical manifestations typically include
constitutional signs and symptoms associated with systemic
inflammation, such as fever, myalgias, arthralgias, and malaise.
• Vessels of any type in virtually any organ can be affected;
most vasculitides affect small vessels ranging from arterioles
to capillaries to venules. Nevertheless, several vasculitides
tend to affect only vessels of a particular size or location

62. • The two pathogenic mechanisms of vasculitis are immune-
mediated inflammation and direct invasion of vascular
walls by infectious pathogens.
• Infections can also indirectly induce a noninfectious
vasculitis
– by generating immune complexes or
– triggering vascular cross-reactivity
• Physical and chemical injury (e.g., from irradiation,
mechanical trauma, and toxins) can also cause vasculitis

64. Noninfectious Vasculitis
I. Immune Complex–Associated Vasculitis
• can be seen in immunologic disorders such as SLE that are associated with
autoantibody production
• Only rarely is the specific antigen responsible for immune complex formation
identified.
• While immune complexes can occasionally be detected in the blood, in most cases
it is not clear whether the pathogenic antigen antibody complexes are deposited
from the circulation or form in situ
• In many suspected cases, even the antigen-antibody deposits are scarce (“pauci-
immune” vasculitides)
– the immune complexes have putatively been degraded by the time of biopsy;
– alternatively, other underlying mechanisms need to be considered

65. • Immune complex deposition is implicated in the following vasculitides:
• Drug hypersensitivity vasculitis e.g., penicillin
• Vasculitis secondary to infections
II. Antineutrophil Cytoplasmic Antibodies (ANCAs)
• are a heterogeneous group of autoantibodies directed against
constituents (mainly enzymes) of neutrophil primary granules,
monocyte lysosomes, and ECs.
• are very useful diagnostic markers; their titers generally mirror clinical
severity.
• Although a number of ANCAs have been described, two are most
important
– Anti-proteinase-3 (PR3-ANCA, previously c-ANCA)
– Anti-myeloperoxidase (MPO-ANCA, previously p-ANCA)

66. III. Anti–Endothelial Cell Antibodies
IV. Autoreactive T cells

67. Giant Cell (Temporal) Arteritis
• is a chronic, classically granulomatous inflammation of
large- to small-sized arteries that principally affects
arteries in the head
• The temporal arteries are not particularly vulnerable
• Vertebral and ophthalmic arteries, as well as the aorta
(giant cell aortitis), also can be involved
• Pathogenesis
– T cell–mediated immune response to an as yet
uncharacterized vessel wall antigen.
– Proinflammatory cytokines (especially TNF) and anti-EC
antibodies also contribute

68. • Morphology
• Involved arterial segments develop intimal thickening (with
occasional thromboses) that reduces the luminal diameter.
• Classic lesions exhibit medial granulomatous inflammation
centered on the internal elastic membrane with elastic
lamina fragmentation;
• there is an infiltrate of T cells (CD4+ > CD8+) and
macrophages.
• Although multinucleated giant cells are seen in
approximately 75% of adequately biopsied specimens
• granulomas and giant cells can be rare or absent
• Segments of relatively normal artery may be interposed.

69.  Clinical Features
• rare before age 50.
• Symptoms may be only vague and constitutional—fever,
fatigue, weight loss
• may involve facial pain or headache, most intense along the
course of the superficial temporal artery, which can be
painful to palpation.
• Ocular symptoms
• Diagnosis depends on biopsy and histologic confirmation.
• Corticosteroids or anti-TNF therapies are typically effective

71. Polyarteritis Nodosa (PAN)
• is a systemic vasculitis of small- or medium-sized muscular arteries
that typically affects renal and visceral vessels but spares the
pulmonary circulation
• There is no association with ANCAs, but a third of patients with PAN
have chronic hepatitis B
• is associated with segmental transmural necrotizing inflammation
• Lesions usually involve only part of the vessel circumference with a
predilection for branch points
• is primarily a disease of young adults but can occur
in all age groups.
• The course is frequently remitting and episodic, with long
symptom-free intervals

72. Infectious Vasculitis
• Arteritis can be caused by the direct invasion of
infectious agents, usually bacteria or fungi, and in
particular Aspergillus and Mucor species.
• Vascular invasion can be part of a localized tissue
infection or, less commonly, can arise from
hematogenous spread
• Vascular infections can weaken arterial walls and
culminate in mycotic aneurysms or
• can induce thrombosis and downstream infarction

73. DISORDERS OF BLOOD VESSEL
HYPERREACTIVITY
 Raynaud Phenomenon
• results from exaggerated vasoconstriction of arteries and arterioles
in responses to cold or
emotion.
• most commonly affects the extremities, particularly the fingers and
toes
• The restricted blood flow induces paroxysmal pallor and even
cyanosis in severe cases
• Involved digits classically show “red, white, and blue” color changes
• Primary- symmetric, severity and extent typically does not progress.
• Secondary- asymmetric, worsens progressively

75. Varicose Veins
• are abnormally dilated, tortuous veins
produced by prolonged, increased
intraluminal pressure with vessel dilation and
incompetence of the venous valves.
• The superficial veins of the upper and lower
leg are commonly involved
• Risk factors: Obesity ,Female sex ,Inactivity
and family history, Prolonged standing

76. • Primary
-Due to genetic or developmental defects in
the vein wall that cause diminished elasticity
& valvular incompetence.
• SECONDARY
-arise from destruction of valves caused by
trauma,DVT,proximal venous
obstruction(pregnancy,pelvic tumor)

77. Clinical features
• Asymptomatic,seek evaluation for aesthetic
concerns.
• Diffuse aeche & heaviness
• Phlebitis
• stasis dermatitis(brawny induration) and
ulcerations
• poor wound healing and superimposed infections
• embolism from these superficial veins is very rare

78. Thrombophlebitis and
Phlebothrombosis
• are largely interchangeable designations for
venous thrombosis and inflammation
• Thrombosis of deep leg veins accounts for
more than 90% of case
• Other sites where venous thrombi may form
are the periprostatic venous plexus in males
and the pelvic venous plexus in females etc.

79. Risk factors for DVT
• prolonged immobilization
• postoperative state
• congestive heart failure
• pregnancy, oral contraceptive use
• malignancy, obesity, male sex, and age over 50
years.
• Inherited defects in coagulation factors

80. Clinical feuture
• Asymptomatic
• distal edema, cyanosis, superficial vein dilation,
heat, tenderness, redness, swelling, and pain
• In some cases, pain is elicited by pressure over
affected veins, squeezing the calf muscles, or
forced dorsiflexion of the foot (Homan sign)