This document summarizes vascular pathology and diseases of blood vessels. It describes the normal structure of blood vessels and the three layers - intima, media, and adventitia. It then discusses different types of arteries and veins as well as blood flow. Various vascular disorders are outlined including atherosclerosis, aneurysms, vasculitis, and problems with veins and lymphatics. The major risk factors for atherosclerosis are identified as age, male gender, family history, hyperlipidemia, hypertension, smoking, and diabetes. The characteristic lesions of atherosclerosis including fatty streaks and fibrous plaques are described. Complications such as plaque rupture, thrombosis, and aneurysm formation are also summarized.

1. 1
Vascular pathology
(Diseases of blood vessels)

2. 2
Normal
Blood vessel walls have three basic
constituents:
1. Endothelial cells
2. Smooth muscle cells
3. Extracellular matrix
elastin, collagen, glycosaminoglycans.

3. 3
The vascular wall

4. 4
Blood vessels have three concentric layers
Intima:
consists of single layer of endothelial cells
separated from media by internal elastic
lamina
Media:
consists of smooth muscle cells
outer portion of media is separated from
adventitia by external elastic lamina.
Adventitia :
lies external to media
consists of connective tissue with nerve fibers
and vasa vasorum.

5. 5
Arteries are of three types
Large or elastic arteries
Aorta, and its large branches
Media is rich in elastic fibers.
Medium sized or muscular arteries
Coronary and renal arteries
Media is chiefly composed of smooth muscle cells.
Small arteries and arterioles
The ones within the substance of tissues and
organs
Capillaries:
Have an endothelial lining but no media
Blood flow is very slow
Well suited for exchange of diffusible substances
between blood and tissues.

6. 6
Veins:
Have larger diameter, larger lumens and
less well organized walls
Predisposed to irregular dilatations,
compression, and easy penetration by tumor
cells.
Have valves that prevent backflow of blood.
Lymphatics:
Thin walled, endothelial lined channels
Drain interstitial fluid and inflammatory
cells back to blood.
Important pathway for spread of bacteria
and tumor cells.

7. 7
Blood flow
Blood flows from
Capillary beds 
Post-capillary venules 
Collecting venules 
Small, medium and large veins.
Leukocyte extravasation and vascular
leakage occurs in postcapillary venules***.

8. 8
Disorders of blood vessels
Arteriosclerosis
Aneurysms and
dissection
Vasculitis
Hypertension
Raynaud phenomenon
Veins and lymphatics
Varicose veins
Thrombophlebitis
Phlebothrombosis
Superior and
inferior vena cava
syndrome
Lymphangits
Lymphedema
Tumors of blood
vessels

9. 9
Pathological changes in blood vessels
Narrowing
or
complete obstruction
Weakening
of
blood vessel wall
Consequences
Atrophy / infarction
Slow
(e.g. by
atherosclerosis)
Acute
(e.g. by thrombus
or embolus)
Dilation, Dissection or rupture
Consequences

10. 10
Arteriosclerosis
Literally means hardening of the
arteries.
A group of diseases that result in
thickening and loss of elasticity of
arterial walls.

11. 11
Three patterns of arteriosclerosis
1. Atherosclerosis (AS):
most frequent and important
2. Monckeberg medial calcific sclerosis:
characterized by calcium deposits in
muscular arteries (uterine and radial)
3. Arteriolosclerosis :
Affects small arteries and arterioles.
Two types:
1. Hyaline arteriolosclerosis and
2. Hyperplastic arteriolosclerosis

12. 12
Case History
A 40-year-old diabetic woman brought to ER with chest
pain.
Past medical history:
Had anginal attacks for many years.
Angina lasted 10-15 minutes - relieved by
nitroglycerine.
Angioplasty relieved symptoms for six months.
Exercise-induced angina returned.
Began having daily anginal attacks that lasted 30
minutes or more.
Hypertensive , Smoker
Medications:
antihypertensives and cholesterol-lowering agents.

13. 13
In the hour prior to her admission:
she had awakened with severe chest
pain, nausea, and dyspnea.
Pain - severe unrelenting - for 45
minutes
not relieved by nitroglycerine.
Vital signs:
HR 105, BP 100/50 (her usual BP was
about 155/95), temp. 1000F.
An EKG and serial cardiac markers were
ordered.

14. 14
Serial cardiac serum marker study

15. 15
Region of Plaque ruptureAtherosclerotic plaqueLumen Occluded
by thrombus

16. 16
Atherosclerosis (AS)
Definition: AS is a disease of large and
medium sized blood vessels characterized by
formation of atheromas deposited in the
intima of arteries.
Responsible for:
1. Ischemic heart disease
1. Acute myocardial infarction
2. Angina pectoris
2. Cerebral infarction (stroke)
3. Gangrene of lower extremities.

17. 17
Atherosclerosis (AS)
The characteristic lesion of AS:
Atheroma or atheromatous or fibrofatty
plaque.
Atheromas have several consequences:
1. Protrude into the lumen of vessels  causing
narrowing and obstructing blood flow.
2. Weaken the underlying media.

18. 18
Atherosclerosis (AS)
Distribution of disease: the
most common vessels
involved in AS in descending
order:
1. abdominal aorta (MC)*
2. coronary arteries
3. popliteal arteries
4. descending thoracic aorta
5. internal carotid artery.

19. 19
Atherosclerosis: Morphology
Initial lesion of AS:
Fatty streak
Characteristic lesion of AS
Fibrous plaque or Atheroma

20. 20Fatty streak

21. 21

22. 22
Fatty streak
Foamy macrophages

23. 23
Fatty streak
The earliest lesion of AS
Is present at all ages including the newborns.
Is composed of lipid filled (cholesterol)
macrophages k/a foam cells
Do not cause disturbance in blood flow (as not
significantly raised)
Fatty streaks may progress to atheromatous
plaques , but not all do so.

24. 24
Fibrous cap
Necrotic center
Media
Atheroma
Foamy
macrophages
Cholesterol
crystals

25. 25
Atheroma or Atheromatous plaque
Is the pathognomonic lesion of AS
It’s a raised focal lesion within the intima of
vessel.
Has a necrotic soft, yellow core of lipid (mainly
cholesterol and cholesterol esters).
Covered by a firm , white fibrous cap.
Composition:
Cells: smooth muscle cells, macrophages and
other leukocytes ( lymphocytes)
ECM : collagen, elastic fibers
Interacellular and extracellular lipids

26. 26
Fibrous cap
Cholesterol
crystals
Vessel Wall
Hemorrhage

27. 27Foamy macrophages
Cholesterol crystal

28. 28
Cholesterol clefts

29. 29
Necrotic Core
Fibrous cap
Lumen
Normal coronary Atheroma

30. 30
Atherosclerosis in the aorta
Fibrous plaque Complicated lesions

31. 31

32. 32
Pathogenesis: Three theories
1. Thrombogenic theory
2. Monoclonal theory (monoclonal proliferation
of SMCs)
3. Reaction to injury theory (the most favored
theory)
Endothelial cell damage in muscular and
elastic arteries leads to eventual
formation of a fibrous plaque.

33. 33
Normal EC injury
Atheroma
Lipid deposits
Collagen
Lymphocyte

34. 34
Reaction to injury theory
EC injury causes:
endothelial dysfunction & increased
permeability
expression of leukocyte adhesion molecules.
Blood monocytes adhere to damaged EC.
migrate into intima and transform into
macrophages
lipoproteins (LDL and VLDL) insudate into
vessel wall at foci of EC injury.
Macrophages accumulate lipid and become
foam cells
Macrophages oxidize the LDL.

35. 35
Platelets adhere to areas of EC injury.
Activated platelets, macrophages, release
factors (e.g.PDGF) that cause migration of
SMC to intima.
SMC proliferate in intima , accumulate lipids
and also produce extracellular matrix (collagen
and proteoglycans).
Lipids accumulation:
within the cells (macrophages and SMC) and
extracellularly.
Development of fibrous cap
Ongoing inflammation:
macrophages  cytokines, O radicals, growth
factors cause lesion progression and
subsequent complications.

36. 36
Complications developing in plaques
Rupture,
ulceration or
erosion
Calcification
Aneurysmal
dilation
Thrombus
formation
Occlusion of lumen
•Partial
•Complete
Cholesterol
emboli
Hemorrhage

37. 37
Normal artery
Fatty streak
Fibrofatty plaque Advanced plaque
Occlusion
by thrombus

38. 38
Complications developing in plaques
1. Erosion, ulceration, or fissuring of plaque surface:
2. Plaque hemorrhage:
3. Thrombosis:
Results from
Turbulent blood flow around the plaque
Damage to endothelial cells 
Thrombus formation.
Can also occur at sites of rupture / ulceration/
fissuring of plaque
4. Aneurysmal dilation:
5. Calcification:
Occurs in areas of necrosis and elsewhere in the
plaque.

39. 39
Complications of Atherosclerosis

40. 40
Complications of Atherosclerosis
1. Aneurysm formation:
• Occurs due to weakening
of underlying media.
• Weakening of vessel wall
 outpouching due to
arterial pressure
• All aneurysms enlarge and
may eventually rupture.
• Abdominal aortic aneurysm
is the MC type.
Abdominal aortic Aneurysm

41. 41
Complications of Atherosclerosis
2. Acute occlusion due to Thrombus formation:
• Can result in ischemic necrosis (infarction) of
the tissue supplied by the vessel:
• Can manifest clinically as:
Acute MI : coronary artery
Stroke : internal carotid artery
Small bowel infarction : superior
mesenteric artery
Gangrene of lower extremities

42. 42Coronary Artery thrombosis

43. 43
Complications of Atherosclerosis
3. Chronic narrowing of vessel lumen:
1. Progressive reduction in blood flow to the
tissue 
2. Chronic ischemia  manifest as
1. Renal atrophy ( renal artery AS)
2. Skin atrophy ( in DM, peripheral vessel)
4. Hypertension:
Due to proximal renal artery atherosclerosis
with activation of renin angiotensin
aldosterone system.

44. 44
Complications of Atherosclerosis
4. Peripheral vascular disease:
due to narrowing of lumens of lower
limb vessels
Gangrene of lower legs
Due to AS of popliteal artery
Impotence, atrophy of calf muscles and
pain in buttocks when walking (Aortoiliac
AS).

45. 45
Complications of Atherosclerosis
5. Source of atheroemboli:
causing renal infarction (MC).
6. Cerebral atrophy:
AS involving the circle of Willis vessels
and/or ICA

46. 46
Risk factors for AS
A: Major:
A. Non-modifiable
1. Age
2. Male gender
3. Family history
B. Modifiable:
1. Hyperlipidemia
2. Hypertension
3. Cigarette smoking
4. Diabetes mellitus
B: Minor:
1. Hyperhomocystinemia
2. C-Reactive proein
3. Obesity
4. Physical inactivity
5. Stress (type A
personality)
6. High carbohydrate
intake
7. Chlamydia pneumoniae
infection.

47. 47
Major risk factors
A. Nonmodifiable
1. Age: most important overall risk factor.
Male >45 female >55 years
2. Male gender
3. Family history: family H/O of premature
CAD, MI, stroke.

48. 48
Major risk factors
B. Potentially Modifiable
1. Hyperlipidemia
2. Hypertension
3. Cigarette smoking
4. Diabetes mellitus

49. 49
Major risk factors
B. Potentially Modifiable
1. Hyperlipidemia :
Increased cholesterol levels (
hypercholesterolemia) enhances AS.

50. 50
Hyperlipidemia
LDL cholesterol: (bad cholesterol)
Transports cholesterol in blood
>160 mg/dL enhances AS
HDL cholesterol: good cholesterol
Mobilize cholesterol from Atheromas
<35mg/dL enhances AS
Increased levels associated with low risk of
AS.
HDL >60 mg/dL negative risk factor for CAD.
Exercise and ethanol ( moderate amounts),
estrogen raise HDL levels
Obesity and smoking lower HDL.

51. 51
2. Hypertension:
Blood pressure >169/95 mmHg.
Antihypertensives reduce the risk of AS
3. Cigarette smoking: enhances AS by damaging
endothelial cells.
Cessation of smoking reduces the risk.
4. Diabetes Mellitus:
Induces hypercholesterolemia enhancing AS.
Incidence of MI twice as high in diabetics as
in nondiabetics.
Increased risk of stroke
Increased risk of AS induced gangrene of
lower extremity.

52. 52
Minor or yet uncertain significance
Hyperhomocystinemia:
Inborn error of metabolism ( increased
homocysteine levels - >100 umol/L).
Due to low folate and vitamin B12 intake.
Increased incidence of Vascular disease.
Markers of inflammation and hemostasis:
Elevated plasminogen activator inhibitor -1
Increased C reactive protein
Associated with AS
Obesity:
Induces HT, DM, hypertriglyceridemia and
decreased HDL

53. 53
Minor or yet uncertain significance
Physical inactivity
Stress (type A personality)
High carbohydrate intake
Chlamydia pneumoniae infection.

54. 54
Monckeberg medial calcific sclerosis
Characterized by
calcium deposits in
muscular arteries
(uterine and radial)
no clinical
consequence unless
associated with
atherosclerosis.

55. 55
Arteriolosclerosis
– Affects small arteries and arterioles.
Two types:
1. Hyaline arteriolosclerosis and
2. Hyperplastic arteriolosclerosis

56. 56

57. 57
Hyaline arteriolosclerosis
Hyaline refers to Pink, glassy appearance of
arterial wall.
Pathogenesis: increased protein is deposited in
the vessel wall that occludes the lumen
Associated conditions:
DM: nonenzymatic glycosylation of protein in
the BM renders them permeable to protein
Hypertension: increased intraluminal pressure
pushes plasma proteins into the wall of the
arteriole.

58. 58
Hyaline arteriolosclerosis
Protein accumulation  narrowing of lumen
 ischemic damage to organs.
Most evident in kidney
Causes loss of renal parenchyma
referred to as benign nephrosclerosis

59. 59
Hyperplastic arteriolosclerosis
Smooth muscle proliferation resulting in wall
thickening and luminal narrowing
Associated condition:
Malignant hypertension and progressive
systemic sclerosis.
Pathogenesis:
acute increase in blood pressure causes smooth
muscle cell proliferation in an onion skin
pattern in renal arterioles.
Narrowing of lumen  ischemic damage .

60. 60

61. 61
Hyaline
arteriolosclerosis
Hyperplastic
arteriolosclerosis