simplified illustration of the pathology of vasculitis and varicose veins for undergraduate medical students

1. Level 2
Semester 3
•
Module (CIBL309)

2. Lecture Title
Vasculitis
varicose veins

3. Instructor information
Dr/ Rana “M. ElSaid” Abou-
ElFetouh Abdalla
Lecturer of pathology
MD., DipRCPath Pathology Department.
Official email:
rana.elsaied@fmed.bu.edu.eg

4. Ilos
• Define vasculitis
• Identify different
pathogenesis of vasculitis
• Classify vasculitis
• Describe selected types of
vasculitis
• Define varicose veins
• Identify risk factors, causes
and effects of varicose veins
• Describe the morphology of
varicose veins.

5. Case scenario
Yassin is a 9-year-old male child, who has been recently
abroad in a trip with his parents and a newborn sister.
After they are home, the parents expressed
constitutional and respiratory symptoms. Taking in
consideration the pandemic circumstances, they were
suspicious for COVID-19 infection. They seaked
medical advice and tested positive for the virus.
Fortunately, Yassin and his sis had no symptoms so they
were kept away from the parents for 14 days.
Two weeks after the family reunion, Yassin expressed
easily fatigability, palpitations and fainted once. The
mother noticed rash on his chest and red swelling of his
legs.
They visited the pediatrician, on examination he
detected cervical and axillary lymphadenopathy.
Considering the pandemic background, he requested a
COVID-19 swap for Yassin that came out positive.

6. Vasculitis
• Def: general term for vessel wall inflammation
• clinical features : depend on the vascular bed
affected (e.g., central nervous system vs. small
bowel).
• signs and symptoms :
➢Generally: include fever, myalgias, arthralgias, and
malaise.
➢Specifically: any organ can be affected; most
vasculitides involve small vessels, from arterioles
to capillaries to venules.

8. etiology
The two most common pathogenic
mechanisms of vasculitis are :
• immune-mediated inflammation
• Infectious
infections can:
➢Directly by invading the vessel wall by
infectious pathogen
➢ Indirectly induce a noninfectious
vasculitis by generating immune
complexes or triggering cross-reactivity.
***In it is critical to distinguish between
infectious and immunological mechanisms,
because immunosuppressive therapy is
appropriate for immunemediated vasculitis
but could very well worsen infectious
vasculitis.

9. NONINFECTIOUS VASCULITIS
The main immunological mechanisms that
initiate noninfectious vasculitis are
(1) immune complex deposition,(eg SLE)
(2) antineutrophil cytoplasmic antibodies
(ANCA) e.g small vessle vasculitis,
(3) anti–endothelial cell antibodies (eg
Kawasaki disease).
(4) Autoreactive T cells cause injury to
vuscular endothelium, forming granuloma
e.g giant cell arteritis

10. 1- Immune Complex–Associated
Vasculitis.
• Many systemic immunological diseases, e.g:(SLE) and
polyarteritis nodosa, manifest as immune complex-
mediated vasculitis.
➢Circulating antigen-antibody complexes may also be
seen (e.g., DNA–anti-DNA complexes in SLE–
associated vasculitis
➢drug hypersensitivity. In some cases (e.g., penicillin)
➢vasculitis secondary to viral infections eg, polyarteritis
nodosa have an underlying hepatitis B infection.

11. 2- Antineutrophil Cytoplasmic
Antibodies.
• ANCAs are a heterogeneous group of
autoantibodies directed against constituents of
neutrophils
• previously classified according to their
intracellular distribution: cytoplasmic (c-ANCA) or
perinuclear (p-ANCA).
• now, they are discriminated based on their target
antigens: (Anti-myeloperoxidase, Anti-proteinase-
3)

12. ANCAs serve as useful diagnostic markers for the ANCA-
associated vasculitides
ANCA titers rise with recurrent disease and are
therefore useful in clinical management.
Although the precise mechanisms are unknown, ANCA
can directly activate neutrophils ------->stimulate
neutrophils to release reactive oxygen species and
proteolytic enzymes -----------> endothelial cell damage.

13. 3- Anti-Endothelial Cell Antibodies.
• Antibodies to endothelial cells may predispose to
vasculitides, e.g: Kawasaki disease.
4-Autoreactive T cells cause injury to
vascular endothelium, forming granuloma
e.g: Giant cell arteritis

14. Diagrammatic representation of the typical vascular sites involved with the more common
forms of vasculitis, as well as the presumptive etiologies. Note that there is a substantial
overlap in distributions.
ANCA, antineutrophil cytoplasmic antibody; SLE, systemic lupus erythematosus.

15. I-Large-Vessel Vasculitis
✓Giant cell arteritis
✓Takayasu arteritis
Giant cell arteritis (temporal
arteritis)
• The most common form of
vasculitis ,specifically among
elderly.
• Vessels affected: principally the
arteries in the head—especially
the temporal arteries,
ophthalmic arteries
•Presents mainly with: Severe
headache and migraine
• Ophthalmic arterial involvement
can lead to permanent
blindness

16. I- Large-Vessel Vasculitis
✓Giant cell arteritis
✓Takayasu arteritis
Giant cell arteritis (temporal
arteritis)
Pathogenesis:
• Autoreactive T cells cause injury to
vascular endothelium, forming
granuloma
• The cause of giant-cell arteritis remains
elusive
• The extraordinary predilection for a
single vascular site (temporal artery)
remains unexplained

17. I- Large-Vessel Vasculitis
✓Giant cell arteritis
✓Takayasu arteritis
Giant cell arteritis
Morphology:
➢Grossly: nodular intimal thickening
reduces the luminal diameter.
➢Microscopically:
• medial granulomatous inflammation
that leads to elastic lamina
fragmentation
• infiltrate of T cells , macrophages &
Multinucleated giant cells.
• Inflammatory lesions are not
continuous ,normal artery may be
interposed.
• The healed stage is marked by

18. B, Elastic tissue stain demonstrating focal destruction of internal elastic lamina (arrow) and
intimal thickening (IT) characteristic of long-standing or healed arteritis.
C, Examination of the temporal artery of a patient with giant-cell arteritis shows a thickened,
nodular, and tender segment of a vessel on the surface of head (arrow)

19. I- Large-Vessel Vasculitis
✓Giant cell arteritis
✓Takayasu arteritis
Giant cell arteritis
Diagnosis:
➢ depends on biopsy and histologic
confirmation.
➢because it is extremely segmental,
adequate biopsy requires at least a
2- to 3-cm length of artery
➢a negative biopsy result does not
exclude the diagnosis.
Treatment
➢corticosteroids is generally effective

20. I- Large-Vessel Vasculitis
✓Giant cell arteritis
✓Takayasu arteritis
Takayasu arteritis
• Age: younger than 40 years
• More common in Asian
females
• Affected vessels: the aorta
and its major branches
• S: ischemic symptoms
(pulselessness disease or
aortic arche disease)

21. Takayasu
arteritis.
• A, Aortic arch angiogram
showing narrowing of
brachiocephalic, carotid, and
subclavian arteries (arrows).
• B, Gross photograph of two
cross-sections of the right
carotid artery taken at autopsy
of the patient shown in A,
demonstrating marked intimal
thickening with minimal
residual lumen.

22. II- Medium-Vessel Vasculitis
• Poly arteritis nodosa (PAN)
• Kawasaki disease
Poly arteritis nodosa (PAN)
• disease involving medium-
sized and small muscular
arteries (renal & visceral aa),
but spares lung vessels
• age: fourth to sixth decades
• Associated with hepatitis B
infection
• Aneurysms or stenosis of the
arteries may be seen

24. II- Medium-Vessel Vasculitis
• Poly arteritis nodosa
(PAN)
• Kawasaki disease
KWASAKI (mucocutaneous lymph node
syndrome, infantile PAN)
• Acute self-limited disease, genetic
susceptibility triggered by infection
(viral).
• Mainly coronary arteries, but any
muscular artery may be involved;
• Age: infants and children (mostly < 4
years)
• S&S: fever for at least 5 days and at
least four of the following clinical
features:
✓conjunctival injection-
✓ cervical lymphadenopathy-
✓ oral mucosal changes-
✓ polymorphous rash-
✓ swelling or redness of the extremities

26. II- Medium-Vessel Vasculitis
Kawasaki disease
• Grossly: Coronary ectasia can
be seen in the acute stage
• Microscopically:
➢Inflammation: lymphocytes and
macrophages first in the intima
and adventitia, then progresses
into the media
➢Panarteritis with neutrophilic
infiltration
➢Healed lesions : fibrosis
• Poly arteritis nodosa
(PAN)
• Kawasaki disease

27. II- Medium-Vessel Vasculitis
Kwasaki
prognosis
• Coronary artery aneurysm develops in
15% to 25% of untreated cases
➢are at risk for rupture in the acute
phase
➢Thrombosis leading to MI
➢become stenotic with progressive
intimal hyperplasia and thrombosis in
the chronic phase
• Poly arteritis nodosa (PAN)
• Kawasaki disease

28. III- Pauci-immune Small-Vessel Vasculitis
e.g:
• Wegener granulomatosis
• Churg-Strauss syndrome (allergic granulomatosis and angiitis)
• Microscopic polyangiitis(hypersensitivity vasculitis or leukocytoclastic
vasculitis)

29. III- Pauci-immune Small-Vessel Vasculitis
• Wegener granulomatosis
• Churg-Strauss syndrome
(allergic granulomatosis
and angiitis)
• Microscopic
polyangiitis(hypersensiti
vity vasculitis or
leukocytoclastic
vasculitis)
• Affects small blood vessels, capillaries
and venules.
• Ch.ch by high serm ANCA level
(diagnostic.
• Wegener granulomatosis: necrotizing
granulomatous vasculitis mainly in lung
and upper airways, glomeruli also
affected.
• Churg-Strauss syndrome: granulomas
mainly skin and kidney, rich in
eosinophils
• Microscopic polyangiitis:necrotizing
vasculitis ,(glomeruli and pulmonary
capillaries)

30. THROMBOANGIITIS
OBLITERANS
(BUERGER DISEASE)

31. • Inflammatory and
occlusive vascular
disorder
• affecting : small and
medium-sized arteries
and veins
• Sites: the vessels of the
distal upper and lower
extremities (tibial and
radial vs)
• sex: young men, who are
heavy smokers;
• age :before 40 years
• Symptoms: advanced
disease may present with
claudication, ischemic
ulcers, or gangrene

33. Pathogenesis.
• The strong relationship to
cigarette smoking is thought to be
due to : direct endothelial cell
toxicity by some component of
tobacco
• Genetic influences are suggested
: an increased prevalence in
certain ethnic groups (Israeli,
Indian Japanese)
Prognosis:
• No laboratory or serologic tests
are useful in establishing
diagnosis
• Cessation of smoking with or
without steroid therapy usually
renders a good prognosis

34. Referral to the case scenario
• Explain Yassin’s symptoms.
• How are these symptoms
linked to the COVID-19 virus.
• Name possible complications
if Yassin’s condition was
neglected.
• Name the most commonly
affected arteries in Yassin’s
case.
• Mention the mechanism by
which these arteries could be
affected.
• Describe the morphology of
these arteries.

35. Varicose veins

36. • Definition: abnormally dilated, elongated, tortuous veins
produced by prolonged increased intraluminal pressure& to lesser
extent by loss of support of the vessel wall.
• Risk factors:
*standing for long periods.
*Age: common over the age of 50 years.
*Sex: more common in females.
• Causes:
1-Deficient support of venous wall either congenital , Familial
tendency
2-Increased pressure inside the veins eg during pregnancy.
3- Incompetence or rupture of valves in the veins
4- senility

37. • Common sites:
a) Superficial lower leg veins,
b) lower end of esophagus,
c) anorectal junction and pampiniform plexus of the spermatic
cord (varicocele).
• Clinical course:
* Varicose dilatation  Venous stasis Congestion, edema
and thrombosis.
* Embolism
* Painful distension of the superficial veins.
* Trophic changes in the skin  Stasis, dermatitis and ulcer.
* Wound infection:  Chronic ulcer (varicose ulcer). May
predispose to metaplasia and carcinoma (Marjolin ulcer).

38. • Morphology:
• Gross: Veins are:
*Dilated, tortuous, elongated with
marked variation in thickness.
*Thinning at point of maximal
dilatation.
*Showing intraluminal thrombosis,
valvular deformities.
• Microscopic:
➢Compensatory hypertrophy in the
smooth muscles
➢subintimal fibrosis,
➢elastic tissue degeneration and
spotty calcification (phlebosclerosis).

39. • Esophageal varices
• Definition: Varicosity of veins at the lower part of esophagus
due to liver cirrhosis  portal hypertension and opened
portosystemic anastmosis.
• Hemorrhoids
• Definition: Varicosity of the hemorrhoidal plexus of veins at
anorectal junction. Prolonged pelvic congestion as repeated
pregnancy, chronic constipation.
• Leading to bleeding, thrombosis and ulceration.

40. References and recommendations
• https://books.google.com.eg/books?id=jheBzf17C7YC&lpg=PA349&v
q=vasculitis&hl=ar&pg=PA349#v=snippet&q=vasculitis&f=false
• https://youtu.be/VfdeBT7e-dc
• https://youtu.be/Ce2TjGY-r1o
• https://youtu.be/LkXQTDb8g2U