1. DISEASES OF BLOOD VESSELS
H.A .MWAKYOMA, MD

2. BLOOD VESSELS Introduction Atherosclerosis Aneurysms
Hypertensive vascular disease
Vasculitis
Diseases of veins
Diseases of lymphatics
Tumors (we will not talk much about it except Kaposi’s sarcoma)

3. Types of blood vessels Arteries: Arterioles: Capillaries:
Elastic arteries: Aorta and large arteries.
Muscular arteries: Smaller arteries.
Atherosclerosis is a disease of large elastic arteries. It rarely affects muscular arteries and does not affects arterioles.
Arterioles:
Smallest elements of arterial system.
Hypertensive arterial disease is primarily a disease of the arterioles.
Capillaries:
Tiniest blood vessels.
Capillaries are rarely affected by disease, except in disseminated intravascular coagulation.

4. Types of blood vessels cont--
Venules
Veins
Venous thrombosis is more common than arterial, because of the slow blood flow and at a lower pressure.
Lymphatics

5. Atherosclerosis A disease of large and medium-sized arteries.
So we are talking about the aorta and its main branches: internal and external iliac, carotids, & subclavian arteries.
The organ arteries are rarely affected such as renal, splanchnic, upper extremity arteries. The intracerebral arteries & lower extremity arteries are the only exceptions.
By far the commonest clinical problem you will face because of atherosclerosis is coronary artery atherosclerosis.
Accumulation within the intima of smooth muscle cells and lipids.
Produces irregular thickening of the wall and narrowing of the lumen.

6. General Comments Arteriosclerosis
Thickening and loss of elasticity of arterial walls
Hardening of the arteries
Greatest morbidity and mortality of all human diseases via;
Narrowing
Weakening

7. Three patterns of arteriosclerosis
Atherosclerosis
The dominant pattern of arteriosclerosis
Primarily affects the elastic (aorta, carotid, iliac) and large to medium sized muscular arteries (coronary, popliteal)
Monckeberg medial calcific sclerosis
Arteriolosclerosis –small arteries and arterioles (hypertension and DM)

8. Non-Modifiable Risk Factors
Age
A dominant influence
Atherosclerosis begins in the young, but does not precipitate organ injury until later in life
Gender
Men more prone than women, but by age about equal frequency
Family History
Familial cluster of risk factors
Genetic differences

9. Modifiable Risk Factors (potentially controllable)
Hyperlipidemia
Hypertension
Cigarette smoking
Diabetes Mellitus
Elevated Homocysteine
Factors that affect hemostasis and thrombosis
Infections: Herpes virus; Chlamydia pneumoniae
Obesity, sedentary lifestyle, stress

10. Pathogenesis of atherosclerosis

11. Normal Artery

12. Atherosclerosis A disease of the intima
Atheromas, atheromatous/fibrofatty plaques, fibrous plaques
Narrowing/occlusion; weakness of wall

13. ATHEROSCLEROSIS Steps in atherosclerosis development
Fatty streak
Fibrous plaque
Atherosclerotic plaque
Calcification plaque
Complication of atherosclerotic plaques.

14. ATHEROSCLEROSIS Fatty streak: Represents the initial lesion
Results from abnormal accumulation of lipoproteins in the intima layer
Mainly localized at arterial bifurcations
Appears since first years of life.

15. ATHEROSCLEROSIS Fibrous plaque:
Is the most characteristic lesion of Atherosclerosis, is composed of:
Monocytes
Macrophages
S.M.C. (Smooth Muscle Cells)
“Foam cells”
*** Lipid-rich “Necrotic core”.

16. Fibrous plaque:

17. Major components of plaque
Cells (SMC, macrophages and other WBC)
ECM –Extracellular Matrix (collagen, elastin, and PGs)
Lipid = Cholesterol (Intra/extracellular)
(Often calcification)

18. Two major processes in plaque formation
Intimal thickening (SMC proliferation and ECM synthesis)
Lipid accumulation

19. ATHEROSCLEROSIS Atherosclerotic plaque:
Proliferation at the intima layer of:
S.M.C.
Macrophages
“Foam cells”
Conective Tissue elements (CTE)
Collagen type I
Elastin Fibers
Glycosaminoglycans
Cholesterol uptake
Calcium deposits
Complication of the plaque

20. ATHEROSCLEROSIS COMPLICATED PLAQUE: Ulceration Thrombosis Growth
Acute thrombosis with oclussion
Disloging and peripheral embolism
Thrombosis
Acute ischemia/necrosis
Growth
Chronic ischemia
Necrosis
Aneurysm development

22. PATHOGENESIS OF ATHEROSCLEROSIS

23. Response to injury hypothesis
* Injury to the endothelium
(dysfunctional endothelium)
* Chronic imflammatory response
* Migration of SMC from media to intima
* Proliferation of SMC in intima
Excess production of ECM
Enhanced lipid accumulation

24. Response to injury hypothesis (I)
1. Chronic EC (Endothelial Cell) injury
EC dysfunction
Increased permeability
Leukocyte adhesion (via VCAM-1)
Thrombotic potential

25. Response to Injury

26. Response to injury hypothesis (I)

27. Response to injury hypothesis (II)
Accumulation of LDL (cholesterol)
Oxidation of lesional LDL
Adhesion & migration of blood monocytes; transformation into macrophages and foam cells
Adhesion of platelets
Release of factors from platelets, macrophages and ECs

28. Response to injury hypothesis (III)
Migration of SMC from media to intima
Proliferation of SMC
ECM production by SMC
Enhanced lipid accumulation
Intracellular & Extracellular (SMC and macrophages)

29. Initiation of Fatty Streak

30. Fatty Streak

31. Fatty Streak-Aorta

32. Fatty Streak-Coronary Artery

33. Fibro-fatty Atheroma

34. Summary of Atherosclerotic Process
Multifactorial process (risk factors)
Initiated by endothelial dysfunction
Up regulation of endothelial and leukocyte adhesion molecules
Macrophage diapedesis
LDL transcytosis
LDL oxidation
Foam cells
Recruitment and proliferation of smooth muscle cells (synthesis of connective tissue proteins)
Formation and organization of arterial thrombi

35. Consequences of plaque formation
Generalized
Narrowing/Occlusion
Rupture
Emboli
Leading to specific problems:
Myocardial and cerebral infarcts
Aortic aneurysms
Peripheral vascular disease

36. Consequences of plaque formation

37. Altered Vessel Function
Vessel change
- Plaque narrows lumen
Wall weakened
Thrombosis
Breaking loose of plaque
Loss of elasticity
Consequence
Ischemia, turbulence
Aneurysms, vessel rupture
Narrowing, ischemia, embolization
Athero-embolization
Increase systolic blood pressure

38. Fibrous cap
Cholesterol clefts
Elastin membrane
destroyed
Neovas.
Calcification
Inflam. cells

39. Foam Cells/Cholesterol Crystals

40. Cholesterol Crystals/Foam Cells

41. Hemorrhage into Plaque

42. Late Changes Calcification Cracking, ulceration, rupture
An example of dystrophic calcification
Cracking, ulceration, rupture
Usually occurs at edge of plaque
Thrombus formation
Caused by endothelial injury,ulceration, turbulence
Organization of thrombus
More thrombus
Encroachment
Weakens vessel wall
Bleeding
Ulceration, cracking and angiogenesis

43. Fibrous Plaques
Complicated Lesions

44. Complicated Lesions

45. Atherosclerosis The major complications of atherosclerosis are
ischemic heart disease without MI
myocardial infarction the most serious complication
Stroke which is cerebrovascular ischemia
gangrene of the lower extremities
the upper extremities are rarely affected if it was due to atherosclerosis however it is common in other diseases like embolization, vasculitis, compression, trauma.
Rarely embolization.
Ischemic heart disease is the leading cause of death in developed countries
while in the developing countries infectious diseases is the leading cause of death.

46. Complicated Lesion/Ulceration/Thrombosis

47. Ulceration/Hemorrhage/Cholesterol Crystals

48. Thrombosis/Complicated Lesion

49. Complicated Lesion/Calcification

50. B: Aneurysms
Localized dilatation of blood vessels caused by a congenital or acquired weakness in the media (by infection or atherosclerosis).
Classification may be based on location, configuration, or etiology.

51. Classification of Aneurysms by Etiology
Atherosclerotic
The commonest large artery aneurysms is caused by atherosclerosis.
It affects mostly the thoracic aorta, abdominal aorta, and its large branches.
Atherosclerosis affecting the arch of aorta or the ascending aorta is extremely rare.
Syphilitic
Uncommon, affects the ascending portion of the aorta .

52. Classification of Aneurysms by Etiology
Dissecting we don’t use this term anymore, it is called “aortic dissection” (cystic medial necrosis)
This will not produce an aneurysm but narrowing of the aorta and occlusion.
Mycotic
Congenital

53. Congenital Aneurysm “Berry Aneurysm”
They are so called Berry aneurysm because they look like small berries توت
Cerebral arteries.
Congenital defect in arterial wall.
Is a cause of subarachnoid or intracerebral hemorrhage.
Usually participated by hypertension

54. Congenital Aneurysm “Berry Aneurysm”

55. saccular or berry aneurysms

56. Unruptured berry aneurysm of middle cerebral artery

57. A ruptured berry aneurysm with subarachnoid hemorrhage leads to sudden onset of an excruciating headache.

58. Hemorrhagic stroke - SAH (Berry Aneurysm)

59. A form of hematoma within the vessel wall.
Dissecting Aneurysms
A form of hematoma within the vessel wall.
History of hypertension or have a weakening in the vessels wall.
Cystic medial necrosis.
Clinical features.
Treatment.

60. Dissecting Aneurysm

61. Dissecting Aneurysm

62. Dissecting Aneurysm

63. Atherosclerotic Aneurysms
Abdominal aorta and common iliac arteries.
Usually fusiform.
May contain a mural thrombosis.
Micro: destruction of arterial wall.
Clinical features

64. Aortic Aneurysm

65. Aortic Aneurysm

66. Aneurysms Pulsatile abdominal mass Abdominal pain Bleeding
Aortic Aneurysm
Pulsatile abdominal mass
Abdominal pain
Bleeding
Atheroembolization
Narrowing of lumen
Usually not a problem

67. Syphilitic Aneurysms
Uncommon, but some studies are suggesting that syphilis is coming back specially in the developing countries.
Aetiology of syphilis: bacterial spirochetes “Treponema pallidum”
Treatment: penicillin
Thoracic Aorta
Syphilitic Aortitits - “tree bark” appearance
Obliterative endarteritis and plasma cell infiltration

68. Syphilitic Aneurysms
In tertiary syphilis, inflammation of the adventitia and the vasa vasorum of the aorta lead to weakening of the media and gradual aneurysm formation.
These aneurysms typically affect the arch of the aorta, and may involve the root of the aorta, leading to incompetence of the aortic valve.
Complications include compression or erosion of adjacent structures as well as rupture

69. Syphlitic Aneurysm of the Aortic Arch

70. Aortic Aneurysm with Thrombus

71. Mycotic Aneurysms
Result of microbial infection (it doesn’t have to be fungal infection, it could be any other infection) and weakening of vessel wall.
Can rupture.
Aorta, cerebral vessels, splanchnic arteries.

72. C: Vasculitis
Inflammation and with or without necrosis of blood vessels, including arteries, veins and capillaries.
May also be known as angiitis.
Many of these disorders involve immune mechanisms such as immune complex deposition, circulating antibodies and various forms of cell-mediated immunity

73. Classification of Vasculitis
Large Vessel Vasculitis:
Giant cell arteritis: Granulomatous arteritis of aorta and large branches. Patients older than 50
Takayasu arteritis: Granulomatous inflammation of aorta & large branches. Patients younger than 50
Medium-sized vessel Vasculitis
Polyarteritis nodosa (classic):
Kawasaki disease: Usually children; coronary artery involvement

74. Classification of Vasculitis
Small Vessel Vasculitis very common
It involves the dermal blood vessels and the renal blood vessels
Wegener’s granulomatosis: Upper & lower respiratory tracts & kidneys.> ANCA present
Churg Strauss syndrome: Lower respiratory tract; asthma; blood eosinophilia
Leukocytoclastic vasculitis: Hypersensitivity vasculitis involving skin
Henoch Schonlein purpura: IgA dominant immune complex deposition in skin, gut & kidney
Microscopic polyarteritis:

75. Classification according to pathogenesis
Infectious: Bacterial, viral, fungal, rickettsial
Immunologic: commonest
Immune complex mediated:Henoch Schonlein; Lupus vasculitis.
Immune complex nephritis is very important, we can see it in purpura or SLE.
Direct antibody attack: Goodpasture’s syndrome it’s a disease that will attack the lungs and the kidney; Kawasaki disease
ANCA associated disorder of the muscles:
Wegener’s granulamatose which is a disease of the lung and the kidney
microscopic PAN, Churg Strauss
So they are termed as vasculitis that present pulmonary-renal syndrome

76. Classification according to pathogenesis –cont--
Unknown:
Giant cell(temporal) arteritis
Takayasu disease
Classic Polyarteritis nodosum

77. Polyarteritis Nodosa
It is called like this because it is segmental and produces small aneurysms that looks like nodes.
An acute, necrotizing vasculitis affecting medium and smaller, muscular arteries.
Patchy involvement of arteries.
Fibrinoid necrosis, acute inflammation, eosinophils.
Thrombosis
Small aneurysms because of the weakening of the wall.
Clinical features: it affects many vessels (polyarteritis)
Kidneys, heart, skeletal muscle, skin, intestine, lung
Association with Hepatitis B
Responds to Steroids and Cyclophosphamide

78. Hypersensitivity Angiitis
Angiitis means an inflammation of an artery.
Group of vascular disorders thought to be in response to exogenous substances, e.g., bacterial products or drugs.
Cutaneous lesions - leukocytoclastic vasculitis.
Due to this many of the vasculitis patients go to dermatology.
Systemic lesions - microscopic polyarteritis, inflammation restricted to the smallest arteries and arterioles.
May be a feature of other systemic diseases such as Lupus Erythematosus.

79. Allergic granulomatosis and Angiitis (Churg-Strauss Syndrome
Systemic vasculitis with prominent eosinophilia
Young persons with history of asthma
Widespread necrotizing vascular lesions of small and medium-sized arteries, arterioles, and veins

80. Giant Cell Arteritis (Temporal Arteritis, Granulomatous Arteritis)
Focal, chronic, granulomatous inflammation of temporal arteries and/or other cranial arteries.
The patient will come complaining of headaches and tenderness at the temporal region, so it will produce pain while wearing a hat.
you don’t have to wait for testing, it needs to be treated with steroids immediately.
Disease of elderly individuals (60 – 70 yrs old).
Artery is cord-like and nodular.

81. Presenting symptoms of headache and temporal pain.
4. Giant Cell Arteritis (Temporal Arteritis, Granulomatous Arteritis) cont--
Thrombus in lumen.
Granulomatous inflammation of arterial wall so the artery becomes really hard.
Presenting symptoms of headache and temporal pain.
Visual symptoms in 50% of patients.
Common symptoms: +/- fever, pain,vessel is very hard, very tender.

82. Wegener’s Granulomatosis
Systemic vasculitis involving nasal sinuses, lungs and kidneys( pulmonary-renal syndrome.)
Anti-neutrophilic cytoplasmic antibodies – ANCA.
Necrosis, granulomatous inflammation, vasculitis of small arteries and veins.
Persistent sinusitis, pneumonitis, hematuria and proteinuria.

83. Takayasu Arteritis Aortic arch, large arteries.
Unknown cause, may be auto-immune.
Worldwide distribution affecting young women.
Intimal thickening, obliteration of lumen, thrombosis.
Pulseless disease.

84. Kawasaki Disease
It attacks the small vessels or the lymph nodes.
Muco-cutaneous lymph node syndrome, because patients have enlarged lymph nodes.
Infancy and childhood.
Unknown cause.
Fever, rash, conjunctival and oral lesions.
Lymphadenitis.
Necrotizing vasculitis.
Coronary artery aneurysms rare.

85. Thrombo-Angiitis Obliterans
You can tell from the name that the patient have thrombosis, obliteration, and vasculitis. Angiitis could affect either arteries or veins.
Also referred as Buerger disease.
Occlusive, inflammatory disease of blood vessels.
Smoking usually in males.
Intermittent claudication.
Can lead to gangrene of the lower limps.

86. Antineutrophil Cytoplasmic Antibodies (ANCA)
We assess and evaluate the immunological findings like ANCA which is important whenever there is vasculitis.
A heterogeneous group of autoantibodies against enzymes mainly in neutrophil granules.
C-ANCA seen in Wegener’s.
p-ANCA seen in microscopic polyarteritis and Churg-Strauss.

87. D: Varicose Veins Enlarged tortuous veins
Risk factors for varicose veins of the legs:
Increasing age
Female sex and has fair skin
Hereditary predisposition
Obesity
Posture specially for long hours travelers by car
Increased venous pressure
Like pregnancy, intra-abdominal tumor, track drivers, surgeons.

88. Varicose Veins
Pathology: dilatation of veins, valvular deformity so the blood will become static, just dilate and becomes engorged.
Aetiology : Weakening of the vein or a deformity
Clinical features: swelling and dull pain
Complications: besides the ugly appearance
stasis dermatitis
Stasis of the blood for a long time will produce a form of dermatitis,so the skin above the vessel becomes reddish & inflamed.
stasis ulcers

89. Varicose Veins At Other Sites
Hemorrhoids in the anal canal.
Esophageal Varices.
Associated with upper GI bleeding & shock.
They are usually seen as a complication of portal hypertension secondary to a chronic cirrhosis.
Varicocele in the scrotum.
The engorged veins and the stasis of blood raises the the temperature of the scrotum, this may result in infertility or low sperm count.

90. VASCULAR TUMOURS AND TUMOUR-LIKE LESIONS
2. BORDERLINE/ INTERMEDIATE
Haemangioendothelioma
3. MALIGNANT
Angiosarcoma
Haemangiopericytoma
Kaposi’s sarcoma
1. BENIGN
Haemangioma
Granuloma pyogenicum
Glomus tumour

91. TUMOURS OF LYMPHATIC SYSTEM
Lymphangioma- capillary, cavernous
Lymphangiosarcoma

92. KAPOSI’S SARCOMA
First described by Moriz Kaposi in 1872 on five patients presenting with ‘sarcoma idiopathicum multiple hemorrhagicum’
In 1912 Sternberg termed this disease Kaposi’s sarcoma-now referred as classical KS
An indolent tumour seen typically in men of mediterranean or east European Jewish origin

93. Kaposis Sarcoma
In 1914 Hallenberg described the first case of African or endemic KS
In 1960 the first report of KS following organ transplant and immuno-suppressive therapy
In 1981 Hymes described the epidemic form associated with AIDS

94. Kaposis Sarcoma The conditions were KS and PCP
The defined social group was homosexual male community
By 1998 nearly people in the USA had developed KS as a result of HIV
Swiss cohort study showed a significant decrease of KS in mid 90s due to HAART

95. HHV-8 Associated Diseases
Kaposis Sarcoma
HHV-8 Associated Diseases
First identified in 1995.
Kaposi’s Sarcoma: Accounts for 80% of all cancers in AIDS patients.
Lesions are flat or raised areas of red to purple to brown discoloration.
May be confused with hemangioma or hematoma.
Strong male predominance.
2/3 of affected patients present oral lesions
Oral lesions are initial presentation in 20% of patients.
Progressive malignancy that may disseminate widely.
Oral lesions are a major source of morbidity and frequently require local therapy.

96. Kaposis Sarcoma
KS associated with gamma-2 herpes virus known as HHV-8(KSHV)
Virus identified using PCR-based techniques in all forms of KS
Classical
Endemic african
Paediatric
Epidemic(HIV related)

97. Kaposi’s Sarcoma HHV-8 transmitted in saliva
In homosexual men rate of HHV-8 is related to the number of sexual partners
Recent evidence from africa on HHV-8 prevalence in children suggests infection is acquired through normal social contacts within the family

98. Clinical features
Classic lesion of KS is a raised macule purplish in colour
Lesions may coalesce into plaques and may ulcerate and bleed
KS may develop at sites of previous trauma
Oedema is almost always a feature
Visceral

99. Clinical features

100. Clinical features

104. AIDS patient with intraoral Kaposi’s sarcoma of the hard palate

105. AIDS patient with intraoral Kaposi’s sarcoma

106. Scrotal skin- KS

107. Endemic Kaposi’s Sarcoma, nodular form

108. Extensive symmetric tumor lesions of Kaposis’s sarcoma in an AIDS patient.

109. STAGING OF KS
Stage I represents localized nodular KS, with more than 15 cutaneous lesions or involvement restricted to 1 bilateral anatomic site, and few, if any, gut nodules.
Stage II includes both exophytic destructive lesions and locally infiltrative cutaneous lesions as locally aggressive KS.
Stage III (generalized lymphadenopathic KS) has widespread lymph node involvement, with or without skin lesions, but with no visceral involvement.

110. STAGING OF KS
Stage IV (disseminated visceral KS) has widespread KS, usually progressing from Stage II or Stage III, with involvement of multiple visceral organs.
A: Associated opportunistic infection(s)
B: Patient is HIV-I seropositive.
C: Cutaneous anergy or other evidence of severe immunodeficiency is present

111. EPIDEMIOLOGIC VARIETIES (TYPES) OF KS

112. Classic Kaposi's sarcoma
older men of Eastern European, Mediterranean, or Jewish descent.
The male/female ratio :(15:1 -3:1).
Bluish-red
macules  papulesplaquesnodules
edema
on the distal lower extremities are often the first sign of KS.
The process is slow and the course is benign.
Visceral or mucosal involvement is found in 10% of patients.

113. Endemic Kaposi's sarcoma (African)
male to female ratio similar to that of classic KS and a mean age of onset of 48 years exept lymphadenopathic type
1.nodular variant = classic KS.
2.florid / infiltrative are aggressive.
3.lymphadenopathic form is particularly common among the young Bantu children . –
Rapid visceral involvement can cause early death.
Skin lesions are sparse

114. Iatrogenic Kaposi's sarcoma
especially true for male patients of Eastern European, Mediterranean, or Jewish origin.
The lesions typically appear several years after transplantation in transplant recipients.
the lesions commonly regress when the medications are reduced or discontinued.
HHV-8 been reported in transplant recipients.

115. Epidemic Kaposi's sarcoma (aids associated)
most common AIDS-associated malignancy
early lesions commonly appear on the face, especially on the nose, eyelids, and ears.
trunk lesions may follow the lines of cleavage.
reddish to pink macules and papules.
Only in prolonged courses do the macules and papules sufficiently coalesce to form plaques

116. Epidemic Kaposi's sarcoma (aids associated)
The lymph nodes and the gastrointestinal tract are commonly involved.
The oral mucosa is the initial site of disease in 10% to 15% of patients, (palate)

117. Other HHV 8 associated diseases
1-Primary effusion lymphoma rare.. DNA copy number is extremely high
IN HIV B cell lymphoma
2.Multicentric Castleman's disease IL6 IN HIV
Fever+ anemia+ hypergammaglobulinemia
3.POEMS syndrome
(polyneuropathy, organomegaly, endocrinopathy, multiple myeloma, skin changes)

118. Mortality/Morbidity Usually die with not from KS
The mean survival rate of patients with KS-AIDS has been approximately months (without treatment)
Fatality: gut perforation, cardiac tamponade, massive pulmonary obstruction or, rarely, brain metastases
Patients with iatrogenic KS tend to have gut bleeding resulting from KS

119. lab
Serum glucose levels may reflect an increased incidence of diabetes mellitus in patients with classic KS.
Immunohistochemical detection of human herpes virus-8
Eosinophilia
cytopenia
Anemia
PCR

120. CONT. CT chest Endoscopy GI angiography may demonstrate KS.
Radionucleotide scans may be USEFUL
Markers for endothelial cells:
Factor VIII–related antigen,
Human leukocyte antigen DR (HLA-DR),
von Willebrand factor, and
The lectin Ulex europaeus I is highly suggestive.
CD34 antigen,

121. (TISSUE BIOPSY): KS - MICROSCOPIC
KS tends to demonstrate increased spindle cells with
vascular slits and vascular structures with a predominance of endothelial cells.
Extravasated erythrocytes and hemosiderin-laden macrophages often are evident.
Some spindle cells may show nuclear pleomorphism.
Early KS may resemble granulation tissue with a diffuse chronic inflammatory infiltrate and capillaries dilated and increased in number.

122. KS - MICROSCOPIC

123. KS - MICROSCOPIC