The document summarizes the structure and functions of the vascular endothelium. It discusses how endothelial cells form a single layer lining the interior of blood vessels, acting as a permeability barrier and performing important roles in coagulation, immune response, angiogenesis, and regulation of vascular tone. Dysfunction of the endothelium is implicated in many vascular diseases such as atherosclerosis, hypertension, diabetes, and sepsis. The integrity of the endothelial layer is essential for organ health.

1. ENDOTHELIUM IN HEALTH
AND DISEASES
Dr. Meghana .P
PG in Pathology

2. VASCULAR ENDOTHELIUM
• Thin layer of cells which lines the interior
surface of blood vessels.
• Body’s largest organ (endocrine).
• One cell thick.
• 1-2 trillion cells.
• Surface area of 400 sq.m
• Weighs 1.5 kg

3. HISTORY
• First described by Rudolf Virchow in capillaries -
simple membrane with flattened nuclei
• Endothelium term - Swiss Anatomist Wilhelm His
• Waldayer -suggested the term restricting to those
cells that make up the innermost layer of blood and
lymph vessels.

4. STRUCTURE OF ENDOTHELIUM
 Thickness is maximum
at the level of nucleus -
2-3 µm
 In capillaries as thin as
0.2 µm
 Diameter - 10-20 µm
Simple Squamous epithelium
(monolayer)

5. STRUCTURE OF ENDOTHELIUM
• Ultra structural level, they have few
characteristic organelles
e.g. 1) transcytotic/ pinocytotic vesicle
2) caveolae
3) Weibel-Palade body

6. ENDOTHELIUM

7. ENDOTHELIUM

8. TRANSCYTOTIC VESICLE
• In exchange vessels.
• Shuttle small amount of extracellular fluid or
blood plasma across the endothelial cytoplasm.
• Facilitates bulk exchange of dissolved gases,
metabolites and nutrients.
• Example: in the lung capillaries

9. CAVEOLAE
• Special type of transcytotic vesicle.
• Typical in vessels of smooth muscle cells.
• Vesicular invagination of cell surface.
• Associated with receptors, enzymes and ion
channels.

10. WEIBEL PALADE BODIES
• Storage granules
• von Willebrand factor and P-selectin.

11. ENDOTHELIAL CELLS
CULTURE – COBBLESTONE APPEARANCE

12. ENDOTHELIAL
HETEROGENEITY
Structural Heterogeneity:
• Continuous endothelium
• Fenestrated endothelium
• Discontinuous endothelium

13. Endocrine glands
GI mucosa
Glomerulus
Liver
Spleen
BM
Skeletal muscle
Heart
Lung
Brain
m
m
m
m
m

14. HIGH ENDOTHELIAL VENULES (HEV)
• Specialized endothelial
cells of post capillary
venules.
• Diameter - 7-30µm
• Site: secondary lymphoid
organs except spleen
• Enable lymphocytes to
enter lymph node.
• Expresses CD34,
MAdCAM-1

15. BLOOD BRAIN BARRIER
• Highly selective
permeability.
• Formed by capillary
endothelial cells.
• Tightness of barrier
depends upon the close
apposition of astrocytes.
• Circumventricular
organs lack it.

16. ENDOTHELIAL PHENOTYPES
Integrins
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17. EMBRYOGENESIS

18. • Earliest blood vessels develop from Blood
islands.
• Blood islands consists of 2 cell lines –
1. Central cells - hematogoniae or hemoblasts
2. Peripheral cells - angioblasts

19. Mesodermal cells
FGF- 2
HEMANGIOBLAST
VEGF
Central blood islands
Hematopoeitic stem cells
( Precursor of all blood cells)
Peripheral hemangioblasts
ANGIOBLAST(Precursor
of blood vessels)

21. ENDOTHELIAL CELL
FUNCTIONS
• Permeability barrier
• Maintenance of extracellular matrix
• Transport function
• Pro and antithrombotic actions
• Regulation of immune responses
• Vascular tone
• Regulation of cell growth
• Angiogenesis

22. MAINTENANCE OF
EXTRACELLULAR MATRIX
Secretes ECM protein
• Basal lamina- collagen, laminin, elastin,
fibronectin
• Glycocalyx - Proteoglycans

23. TRANSPORT
• Simple diffusion - O2, CO2
• Active transport - Glucose, Amino acids,
Electrolytes
• Pinocytosis - Small molecules,
Soluble proteins
• Receptor mediated
endocytosis - GF’s, Antibodies,
LDL, Transferrin,
MHC complexes

24. REGULATION OF IMMUNE
RESPONSES
• Secretion of interleukins (IL-1,IL-6,IL-8)
• Expression of MHC II molecules.
• Expression of cell adhesion molecules and
their receptors.
• Leukocyte rolling.

25. LEUKOCYTE MIGRATION THROUGH THE
BLOOD VESSELS

26. PRO AND ANTITHROMBOTIC
ACTIONS
• Smooth surface of endothelium - glycocalyx
• Negative charge on endothelial cells –
glycosaminoglycans.
• Anticoagulants and antithrombotic substances
- intact endothelial surface.
• Prothrombotic substances - damaged
endothelium.

28. REGULATION OF CELL
GROWTH
Secretion of –
• Growth stimulating factors – PDGF, GM-CSF,
FGF
• Growth inhibiting factors – Heparin, TGF-β

29. VASCULAR TONE
Secretion of –
Vasoconstrictors - Endothelin-1
Thromboxane (TXA2)
Angiotensin II
Vasodilators - Prostacyclin (PGI2)
EDHF
Nitric oxide (NO)

30. NITRIC OXIDE
• Soluble gas produced from arginine.
• Nitric oxide synthase – 3 isoforms
1. eNOS
2. nNOS
3. iNOS

32. NITRIC OXIDE
• Stimulus : Shear stress, inflammation,
acetylcholine, substance P, bradykinin,
serotonin, endothelin, thrombin
• Inactivated by: hemoglobin
• Action lasts for 3-6 sec

33. ENDOTHELIN
• Endothelial cells produce endothelin-1 (ET1)
• Potent vasoconstrictor
• Secretion – regulated via transcription of ET1
gene

34. ENDOTHELIN
STIMULATORS
• Angiotensin II
• Catecholamines
• Growth factors
• Hypoxia
• Insulin
• Oxidized LDL
• Shear stress
• Thrombin
INHIBITORS
• NO
• ANP
• PGE2
• Prostacyclin

35. ANGIOGENESIS
• Formation of new blood vessels from pre-existing
blood vessels.
• Stimulants : Pregnancy
Hypoxia
Inflammation
Trauma
Tumors
• Facilitated by -VEGF
• Also by Ang-1, FGF, α5β1 integrin

36. PHYSIOLOGICAL
ANGIOGENESIS

37. ANGIOGENESIS
Tumor vessels are -
• Tortuous
•Dilated
•Uneven diameter
•Excessive branching
&shunting
•Lack perivascular
cells

38. ENDOTHELIAL ACTIVATION

39. ENDOTHELIAL DYSFUNCTION

40. ATHEROSCLEROSIS
• Disease of large and medium sized muscular
arteries.
• Characterized by-
1. Endothelial dysfunction
2. Vascular inflammation
3. Atheroma /atherosclerotic plaque

41. PATHOGENESIS OF
ATHEROSCLEROSIS
Intima

42. ATHEROSCLEROSIS

43. HYPERTENSION
• Angiotensin converting enzyme(ACE) is an
endothelial enzyme.
• Converts angiotensin I to angiotensin II

44. SMOKING
• Nicotine- opens up intercellular junction and
allow large molecules to pass through the wall.
• Such toxins can potentiate degenerative changes
in the blood vessels and lead to vascular disease.
• Prolonged smoking increase death rate from IHD
by 200%
• Smoking cessation decreases that risk
substantially.

45. ENDOTHELIUM AND STROKE
• Production of EDCF- counteracts the normal
dilator effect of NO.
• Reduced activity of NOS.
• Presence of Hemoglobin in subarachnoid
haemorrhage inhibition of NO
vasospasm

46. ENDOTHELIUM AND DIABETES

47. ENDOTHELIUM AND CKD
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48. ENDOTHELIUM AND SEPSIS

49. THROMBOTIC
MICROANGIOPATHIES
• TTP & HUS are caused by insult that
activates platelets and deposit as thrombi in
microcirculation.
• Superimposition of endothelial injury may
further promote platelet micro aggregate
formation.

50. VON WILLEBRAND DISEASE
• vWF - interaction and adhesion of platelets to
ECM.
• Genetic absence of this factor ( AD, rare AR)
von Willebrand disease

51. TUMORS OF ENDOTHELIAL CELLS-
WHO CLASSIFICATION
A) BENIGN
1. Hemangiomas -sub cutaneous, capillary, cavernous,
arteriovenous, venous, intramuscular, synovial
2. Epitheloid Hemangiomas
3. Angiomatosis
4. Lymphangioma

52. TUMORS OF ENDOTHELIAL CELLS-
WHO CLASSIFICATION
B) INTERMEDIATE (LOCALLY AGGRESSIVE)
1. Kaposiform hemangioendothelioma
C) INTERMEDIATE (RARELY
METASTASIZING)
1. Retiform hemangioendothelioma
2. Papillary intralymphatic angioendothelioma
3. Composite hemangioendothelioma
4. Kaposi sarcoma

53. TUMORS OF ENDOTHELIAL CELLS-
WHO CLASSIFICATION
D) MALIGNANT
1. Epitheloid hemangioendothelioma
2. Angiosarcoma of soft tissue

54. SUMMARY
• Endothelial cells play a vital role in health and
integrity of every tissue of the body.
• Not only a permeability barrier, but also
involved in - immune response, growth
regulation, coagulation, production of ECM
components, modulation of blood flow and
blood vessel tone.
• Thus, they are life-supporting tissue extending
and remodeling the network of blood vessels,
and enabling tissue growth, motion and repair.

55. • Dysfunction of endothelium has been
implicated in virtually every type vascular
disease and hence integrity and proper function
of endothelium is essential for proper organ
function and good health.
SUMMARY

56. REFERENCES
• Harrison’s internal medicine, 17th edition.
• Hematology: Basic Principles And Practice, Ronald Hoffman,
6th edition.
• Hemostasis and Thrombosis: Basic Principles and Clinical
Practice, Victor and William, 6th edition.
• Rajendran P, Rengarajan T, Thangavel J, Nishigaki Y,
Sakthisekaran D, Sethi G, Nishigaki I. The Vascular
Endothelium and Human Diseases. Int J Biol Sci 2013;
9(10):10571069.
• Pathological basis of disease : Robbins and Cotran, 9th edition.
• WHO classification: tumors of soft tissue and bone.

57. THANK YOU