Blood vessel disease ,Atherosclerosis leading to IHD,CVD,CAD Commonest Arterosclerosis

1. ATHEROSCLEROSIS
Dr.Jyoti Priyadarshini Shrivastava
Associate Professor
Department of Pathology
Gajra Raja Medical College

3. PATHOLOGY
 Bridging Discipline
 General Pathology and Systemic /Special Pathology
CORE OF PATHOLOGY
1.Etiology
2.Pathogenesis
3.Morphology
4.Clinical Significance

4. BLOOD VESSELS
Closed circuits for the transport of
blood from the heart to the tissues for
exchange of gases and nutrients and
vice versa.
Arteries
Veins
Capillaries

5. The Vascular System
 The arterial system - high-pressure system, so
arteries have thick walls that appear round in cross
section.
 The venous system - lower-pressure system,
containing veins that have larger lumens and thinner
walls. They often appear flattened.
 Arteries, arterioles, venules, and veins are composed of
three tunics known as the tunica intima, tunica media,
and tunica externa.
 Capillaries have only a tunica intima layer
(An adult's blood vs. be closer to 100,000 miles long)
(300 million capillaries in the human body. )
Capillary bed: network of 10–100 capillaries connecting arterioles to venules

7. Distribution of Blood
•Systemic circulation 84%
•Systemic veins 64%
•Systemic arteries 13%
 •Arterioles 2%
 •Muscular arteries 5%
 •Elastic arteries 4%
 •Aorta 2%
•Systemic capillaries 7%

10. ATHEROSCLEROSIS

11. INTRODUCTION
Atherosclerosis is a condition
where the arteries become
narrowed and hardened due to a
build up of plaque in the artery
wall.

12.  Sclerosis= Hardening
 Arteriosclerosis=Hardening of Arteries
 Three Patterns:
 1.Atherosclerosis
 2.Monkeberg’s Medial calcific sclerosis
 3.Arteriolosclerosis
 Hypertension
 Diabetes Mellitus
 4.Senile Arteriosclerosis

13. DEFINITION
Atherosclerosis is a specific form of
arteriosclerosis affecting intima of
large(elastic) and medium sized muscular
arteries characterised by fibrofatty plaques or
atheromas.
Athero- porridge,gruel
Sclerosis-Scarring/Connective tissue
Atherosclerosis: Hardening and loss of elasticity

14. Points to remember
1.Progressive disease
2.Intima
3.Fatty streaks(Precursor)
4.Eccenteric lesions at branching points

17. PLAQUE
Plaque is a sticky substance made up of fat,
cholesterol, calcium, and other substances
found in the blood.
The presence of the plaque induces the
muscle cells of the blood vessel to stretch,
compensating for the additional bulk, and the
endothelial lining thickens, increasing the
separation between the plaque and lumen.
Plaque hardens and narrows your arteries.
That limits the flow of oxygen-rich blood to
your body.

20. Masson trichrome staining is used to discriminate collagen fibers from
muscular tissues on histological slides.

21. SITE OF LESION
 SITE: Large(Elastic) ,Medium sized(muscular)
arteries
 Arteries: AORTA(Post.wall)
Abdominal aorta (Aneurysm)
Coronary
Cerebral
Renal
Peripheral vessels
Mesenteric vessels

23. Aetiology

24. ETIOLOGY
 Major risk Factors:
Modifiable-Dyslipidaemia, HTN, D.M., Smoking
Non- Modifiable-Age, Sex, Genetic Factors, Family/race
(Constitutional)
 Emerging Risk Factors:
Environmental factors
Obesity
Hormones
Physical inactivity
Stress
Homocystinuria
Alcohol
Prothrombotic factors
Infections(Herpes,CMV)
High CRP

25. Two risk factors –Increased risk
by 4 Folds
Three risk factors- Increased
risk by 7 Folds

26.  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 60--7070 about equal
frequency.
Oestrgen and HDL are protective .
 Family History
Familial/racial cluster of risk factors- Blacks
Genetic differences

27. Emerging Risk Factors
 1.Environmental influences: > in developed nations,
Western world
 2.Obesity: >20% overweight
 3.Physical inactivity/lack ofexercise
 4.Stress:Type A personality
 5.Homocystinuria(inborn error of metabolism)
 6.Infections:CMV,HSV, C.pneumoniae
 7.CRP:

28. Major risk Factors
 Modified by Life Style /Pharmacotherapy
LIPID DISORDERS:
Virchow-Cholesterol crystals in Atheromatous lesions
Hyperlipidemia :
(Increased Cholesterol,Triglycerides,Liporoteins)
Major factor
Directly proportional
EVIDENCES:
1. Bad cholesterol(LDL,IDL)-Connstituent of plaque
2. HDL: Removes cholesterol
Ratio of LDL:HDL::4:1
3. Experimental animals
4. Diseases inducing hypercholesterolemia- Dm, Nephrotic Syndrome,
Myxoedema,Xanthomaosis
5. IHD more in H+chol.

29. HYPERLIPIDEMIA
 Higher-than-normal levels of cholesterol, triglycerides,
and other lipids and Lipoproteins in the blood.
1.Familial
2.Acquired

30. FAMILIAL HYPERLIPIDEMIA
 Familial :Inherited Autosomal Recessive/Dominant
trait.
 LDL receptor via apolipoprotein E
 Gene mutation of apolipoprotein, Hepatic Lipoprotein
receptors, Lipoprotein lipase enzyme.
 LDL accumulation- Atheromas
Xanthoma

31. ACQUIRED HYPERLIPIDEMIA
I.Dietary Factors:
Cholesterol and Saturated Fats> 40%
Saturated fat intake > 10% of total calories.
(single bonds,stable,deposited under skin)
II.Diseases:
Diabetes
Myxoedema
Nephrotic syndrome
Hypothyroidism
III. Obesity and Smoking
IV. Progesterone
V.Hypertension :
(lipid lowering drugs reduces the chances of IHD)

32. PATHOGENESISMultifactorial Process

33. Insudation Hypothesis/Lipid theory/Response
to Injury Hypothesis(Virchow)
(Rudolf Ludwig Carl Virchow "the father of modern
pathology")
 Imbibed lipids from blood
 Cellular proliferation of Intimal cells

34. Encrustation Hypothesis/Thrombogenic
theory:(Rockitansky)
Atheroma encrusted on arterial wall
Thrombus –platelets,fibrin and leucocytes
Thrombosis not a sole factor
Merged with Response -to-injury Hypothesis

35. Reaction to Injury Hypothesis(Ross)
Widely accepted
Encorporates Lipid theory + Thrombogenic
theory

36. Components of Reaction-to-injury
Hypothesis
1.Endothelial Injury
2.Intimal SMC proliferation
3.Role of Blood Monocytes
4.Role of Dyslipidemia
5.Thrombosis

37. Endothelial injury
 1.Mechanical trauma
 2.Haemodynamic forces(Branching/openings)
 3.Immunological/chemical mechanisms
 Metabolic agent:
Chronic Dyslipidemia
Homocystinuria
 Infections
 Hypoxia
 Radiation
 Carbon monoxide
 Tobacco products

38. Intimal SMC proliferation
 Enothelial damage
 Subendothelium exposed
 Adherence,Aggregation and platelet release reactions
 Inflammatory cells enter
 Proliferation Of SMC’s
 (IL-1,TNF)Production of extracellular matrix
 PDGF,FGF----SMC proliferation in Intima
 TGF-B andIFN- Gamma activate T lymphocytes.Collagen
synthesis
 NO and Endothelin-SMC,Collagen,Elastic fibres

39. Role of Blood Monocytes
LDL in monocyte---Oxidised LDL----foam
cells.
For endothelium—Oxidised LDL-----
Cytotoxic.
Death of Foam cells by Apoptosis releases
Lipids to form Lipid Core of Plaque.

41. Role of Dyslipidemia
 1.Endothelial Injury and Dysfunction
 2.Increased permeability
 3.Foam cell formation by Oxidised LDL,
(HDL—Anti atherogenic)

42. THROMBOSIS
 1.Endothelial damage
 2.Platelet aggregation
 3.Inflammatory reaction
 4.Thrombus formation+Foam cells
 5.Atheromatous Plaque
 6.Fibrin and WBC’s

44. Monoclonal Hypothesis
 SMC proliferation is initial event
 Monoclonal proliferation(Neoplasms)
 SMC show only one form of G6PD isoenzymes.
 Monoclonality is due to mutation by
Chemicals
Metabolites
Viruses

49. MORPHOLOGY

50. STAGES
Intimal Thickening
Fatty Streaks and Dots
Fibrous Plaque
Atheroma
Atherosclerosis

51. Fatty Streaks
At Birth
Asymptomatic
Dots or streaks
1 mm in size
Disappear with age
Aorta(Post.wall),major arteries

52. Earliest Visible Lesion

54. Gelatinous Lesions
 At Birth
 Oval ,Round
 Gross: Grey elevations
 1 cm. in diameter
 Microscopy: Increased Ground substance and
Thinned endothelium.
 Intermediate, transitional stage in the complex
histogenesis of the atherosclerotic plaque.

55. Atheromatous/fibrofatty plaque
 Site:Abdominal aorta
Descending thoracic aorta
Aortic arch
Ostia: Iliac
Femoral
Carotid
Coronary
Cerebral

56. Atheromatous Plaque
Gross:
White to yellowish
1-2 cm
Raised
Cut Section:
1.Fibrous Cap
2.Necrotic centre

57.  Fibrous cap
Superficial luminal part
Covered by enothelium
SMC,Dense connective tissue, ECM(Proteoglycans, collagen)
 Cellular Area
Macrophages
Foam cells
Lymphocytes
SMC
+/- Lipids
 Deeper central soft core
Lipid,Cholesterol cleft, Fibrin,NecroticDebris, Lipid laden Foam cells
 Advanced Lesion: Thick fibrous cap

58. Atheromatous Plaques

59. Typical Atheroma/Type IV lesion

60. Complicated Plaques

61. Calcification
Intima and necrotic area
Different from Monckebergs degeneration-Medial
calcification

63. ULCERATION

64. THROMBOSIS

66. HAEMORRHAGE
Intimal haemorrhage from ulceration
Common in coronary arteries
Hematoma contains hemosiderin laden
macrophages

67. ANEURYSM FORMATION
 Basically Intimal disease
 Advanced----Media and adventiia show secondary
changes
 Media---Atrophy
Thinning
Fragmentation of IEL
 Adventitia: Fibrosis
Inflammation

70. Rupture of Aortic Aneurysm

72. Clinical effects of Atherosclerosis

73. Atherosclerosis Score Index (ASI)
Whole-body magnetic resonance angiography
(WB-MRA) has shown its potential for the
non-invasive assessment of nearly the entire
arterial vasculature within one examination.
Association between the GES(Gene
Expression Score ) based on age, sex and
peripheral blood cell expression levels of 23
genes measured by quantitative real-time
PCR (qRT-PCR)and coronary arterial Plaque
Burden and Stenosis by CT-angiography

74. Atherosclerosis Scoring
 The traditional Framingham Risk Score
 [QRISK score (http://www.qrisk.org)
 Reynolds Risk Score
(http://www.reynoldsriskscore.org)]
 The Society for Heart Attack and Eradication (SHAPE)
guidelines ; they advocate assessment of biomarkers in
all intermediate risk patients, a position not yet
endorsed by NLA. ACC/AHA
 Guideline for Assessment of Cardiovascular Risk in
Asymptomatic Adults (2010) lists a few diagnostic tests
as Class IIa recommendations.

75. THANK YOU