Chapter 3 - Vessel wall biology Flashcards by Gary Yang

Vessel wall characteristics: artery, vein, lymphatic

Collagen content
Elastic fiber content
Central pressure
Shear stress
Stretch force
Pulsatility
Compliance
Oxygen tension
Intrinsic propulsion
Valves

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3 layers of the arterial wall

Tunica intima

Tunica media

Tunica adventitia

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Thickness of vascular endothelium in capillaries/veins vs aorta

0.1 microm in capillaries/veins

1 microm in aorta

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Coating on the vascular endothelium to reduce friction

Glycocalix

Thickness varies across vascular tree

Sheared off in inflammation to allow leukocyte attachment

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Distance of intercellular space in the vascular endothelium

15-20 nm

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Define: pinocytic vesicles

allow movement of material from vessel lumen into the wall

primarily in muscular small blood vessels, largely in heart and lung, less in retina and brain

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Size of fenestrae on vascular endothelium

70 nm

majority have 5-6 nm nonmembranous diaphragm

Located in capillaries of exocrine/endocrine glands, GI mucosa, choroid plexus, glomeruli, renal tubules

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Location of nonfenestrated continuous endothelium

Brain, skin, heart, lung

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Location of discontinuous endothelium

size of their fenestrations

Liver

100-200 nm without diaphragm

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Zones of the basal lamina

Lamina rara (inner): laminin (glycoprotein)

Lamina densa: fibrillar, dense next to interstitial connective tissue; type IV collagen

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Endothelium in normal functioning

Quiescent state

Cell-cell contact inhibit proliferation

Low mitotic index

Secrete ECM components (fibronectin) and basement membrane (laminin, proteoglycans, collagen IV)

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Composition of basal lamina

glycoprotein

adhesion molecule (laminin, fibronectin, entactin, thrombospondin)

proteoglycans (heparan sulfate chains)

microfibrils of collage IV and V (5 nm in diameter)

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Sublayers of the tunica intima

Endothelium

Basal lamina

Reticular layer

Internal elastic lamina

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Reticular layer of the tunica intima

Composition

Collagen types I and III

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Proteoglycan: what it is, function in vascular wall, main types

macromolecules that influence viscoelasticity, permeability, lipid metabolism, homeostasis, thrombosis

Heparan sulfate
Dermatan sulfate
Chondroitin sulfate

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Collagen: what it is, function in vascular wall, main types

Type IV collagen: made by EC and SMC; in the basement membrane
- high proline triple helix structure: affects flexibility and enhance cell adhesion and migration

Type V collagen: pericellular, made by EC and SMC
- bind interstitial collagen to cell/basal laminae

Type I collagen: major collagen; main type in human aorta intima and media

Type III collagen: major collagen; subendothelium of young adults

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Describe: laminin

noncollagenous basement membrane

pivotal role in cell-basement membrane interactions

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Describe: fibronectin

large glycoprotein with two disulfide-linked subunits

promote adhesion of molecules, spread of mesenchymal and epithelial cells and proliferation and migration of embryonic and tumor cells

Regulartes cell differentiation, shape, cytoskeletal organization

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Thickness of internal elastic lamina

70-100 nm

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Organization of the internal elastic lamina

Elastin organized into fenestrated cylindrical lamellae

Lamellae separated from neighbors by single layer SMC

Thickness and circumference can change with changes in media (in disease)

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Tunica media: composition

Vascular SMC, elastin, collagen fibers arranged in organized fashion

SMC surrounded by basement membrane (laminin, collagen IV, heparans ulfate proteoglycan, entactin/nidogen, fibronectin)

prevents migration of SMC
maintains contractile state (not synthetic state SMC)

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Synthetic state of SMC

Migrate to intima

proliferates

secrets ECM components

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Strength layer collagen type of SMC

Type III

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Average tangential tension per medial layer

2000 dynes/cm

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Elastic arteries vs musclar arteries

Elastic arteries: well-defined elastic lamellae and collagen - aorta, brachiocephalic trunk, iliac arteries - lamellar units: elastin, collagen, SMCs Muscular arteries: SMCs with fewer connective tissue fibres - predominate in 2nd or 3rd order branches of elastic arteries

Average number of lamellar units in aorta

40-60 units 12-17 microm from arterial lumen Number of lamellar units decrease from heart to peripheral arteries

Fascicles of the tunica media

Further organization of the SMC and branching elastic fibres Each fascicle = sheath of basal lamina and collagen fibrils Orientation of fascicle is in same direction of imposed tensile stress - circumferentially in straight segments - smaller and less uniform in size and orientation at bends and branching points

Tunica adventitia: composition

Vasa vasorum Nerves: control SMC function Fibrous connective tissue (elastic + collagen fibers) Lymphatic network

Vaso vasorum: which vessels have them

Arteries \> 200 microm Arteries where medial layer \> 29 lamellar units Supply outer part of media while inner part is supplied by lumenal flow Arise from parent artery at branch junctions

Pathophysiology of vasa vasorum in diseases

Flow affected by hypertension, mural stresses and deformations

Anatomy: track of the aorta

Left ventricle (3 cm) arch back over root of left lung descend within thorax on L of vertebral column through aortic hiatus ends opposite to lower L4 (1.75 cm)

Differences in small arteries vs larger arteries

Smaller arteries are musclar arteries more innervated and principal regulators of peripheral resistance thinner tunica intima well defined internal elastic lamina incomplete external elastic lamina

Unique anatomic features of coronary arteries

``` Thicker adventitia (collagen, elastic fibers, adipose tissue - predominate collagen \> elastic: greater tensile strength, low stretch ``` Richly innervated SMC in medial and adventitia Branching sites of artery show normal periodic thickening of intima

Define: musculoelastic cushions

Thickening of intima at branching sites in coronary arteries May contribute to atherosclerosis May be a normal phenomenon

What vessel type is responsible as the chief source of vascular resistance

Arterioles

Composition of capillaries

Only tunica intima Endothelium, basal lamina, pericytes (incomplete surrounding)

Function of pericytes

Contractile properties: regulate flow in capillaries Differentiate into endothelial or SMC in remodeling and repair

Three types of capillaries

Continuous: selective filter by endothelium and lamina Fenestrated: openings in endothelium; complete basal lamina Discontinuous: incomplete endothelium, incomplete basal lamina - sinusoid capillaries in liver, spleen, red bone marrow

Diameter of capillaries

4-15 microm

Size of fenestrations in fenestrated capillaries

50-60 nm

Size of Intercellular gaps in discontinuous capillaries

0.1 - 1 microm

Principle of vascular remodeling

Increase circumferential stress = increase SMC hypertrophy, collagen, elastin production Decrease circumferential stress = vascular atrophy

Effect of chronic shear stress

Enhance L-arginine/NO pathway in endothelium --\> mRNA cGMP --\> matrix metalloproteinases (MMP-2, MMP-9) - apoptosis, enlargement, vascular remodeling Upregulation Type III NO synthase

Effect of age on arterial circumference

Medial thickness unchanged Intimal thickness increased Lumen diameter increased Maintain consistent tensile strength

Principle of pressure-induced arterial wall crush

When there is limited vascular stretch, intraluminal pressure causes crush (same as in PTA treatment) - DNA synthesis, cell proliferation (FGF2)

Endothelium response to shear stress

Align in direction of stress (elongation of cells) Redistribution of intracellular stress fibers and quantity Higher stress fibers (actin, myosin, contractile proteins) \*only occurs in arteries, not in veins Activate stretch-induced ion channels, phospholipids and integrins Upregulate PDGFs alpha and beta, TPA, TGF beta, endothelin-1, NO synthase III and ICAM-1

Different vessel wall layer response to cyclic/circumferential stretch

Endothelium: Cell proliferation (max in 1st day of exposure) - Increase total protein content SMC: change orientation (align perpendicularly to direction of strain vector; annular) - increase type I and III collagen - increase elastin Fibroblast: increase type II:I collagen ratio

Venous endothelial cells produce these

Vasorelaxants: prostacyclin (PGI2) and NO

Venous media differes from arteries

Thinner layer, less well developed Contribute to varicosity development SMC held in quiescent state TGF beta reduces mitogenesis and stabilize matrix Heparin-like molecule neutralize FGF to downregulate proliferation

Venous adventitia differs from arteries

Thickest layer in large veins can blend with the media Vasa vasorum penetrate deeper

Vasa vasorum in veins differ from arteries

Much more extensive and penetrate deeper into adventitia Likely due to lower oxygen tension in venous blood

Cellular signalling pathway for differentiation of artery and vein

Effect of Ephrin-B2 signalling

Regulates mural-cell migration, spreading and adhesion during wall assembly Absence will limit mural cell recruitment

Effect of EphB4

limits cell proliferation, decreased intimal and medial thickening

Vein composition difference with artery

Vein more collagen, nearly no elastic fibers Veins has diminished internal and external elastic laminae

Types of venules (3) Characteristics and functions

Postcapillary venules: 10-50 microm in diameter - endothelium and pericytes, no SMC - loosely organized endothelium is leaky - thin basal lamina - main site for WBC diapedesis and tissue exudate Collecting venules: similar with more pericytes Muscular venules: clearly defined intimal layer, no elastic fibers, tunica media with 1-2 layers of SMC

Average size range of small-medium veins

1-9 mm diameter

Vessel wall anatomy of the venae cavae

Intima: fibroelastic tissue Media: narrow with circumferentially oriented SMC Adventitia: thick, longitudinally oriented collagen and SMC Elastic fibers scattered throughout all layers; small amounts of cardiac tissue near connection to heart; extensive vasa vasorum in adventitia

Threshold of reverse velocity for venous valve closure

30 cm/s

Composition of venous valves

Collagen-elastic fiber core of connective tissue covered by thin endothelium

General location of venous valves

Distal to confluence of minor venous branches forming larger veins

Direction of intervenous flow in the lower extremity

Caudal to cephalad Superficial to deep Deep to superficial in dorsum of foot

Venous valve changes in venous insufficiency

Reduction in valves per unit length Infiltration by monocytes and macrophages Increased MMP-2 and MMP-9 favoring accumulation of ECM

Lymphatic drainage system names from extracellular back to vein

Extracellular matrix Lymphatic capillaries (initial lymphatics; terminal lymphatics) Precollecting lymphatics Collecting lymphatics Trunks Ducts

Initial lymphatics: location

Blind-ended vessels - connective tissue of skin and liver - mucous membrane of resp, GI, GU

Diameter of initial lymphatics

10-60 microm

Thickness of initial lymphatics and wall composition

50-100 nm monolayer nonfenestrated endothelial cells Discontinuous or absent basal lamina

What is the endothelial microvalve

Gaps between endothelial cells are 10 microm When vessels collapsed, gaps open allowing for lymphatic entry When vessels filled, cells expand and close gaps - therefore unidirectional flow

Precollecting lymphatics propulsion system

Secondary valves: bicuspid, irregularly spaced, sometimes single leaflet SMC contractions Primary valves as in initial lymphatics

Collecting lymphatics: wall anatomy

No more primary valve mechanism 3 typical vessel layers - intimal monolayer - SMC, collagen, elastic fiber 1-3 layers (helicoidal manner) - adventitia: fibroblast, connective tissue, nerve terminals More regularly spaced secondary valves

Lymphangions definition diameter and length

Space between two secondary valves In head and neck: 0.2 mm diameter, 2 mm length Lower extremity: 1-2 mm diameter, 2 mm length Innervated by SNS and PNS

Lymph node anatomy

Secondary valves anatomy

Lymphatic vessel wall bulges at secondary valves - causes string of pearls because of diameter changes Monolayer of endothelial cells on a collagen matrix

Cisterna chyli Define

Confluence of lymphatic vessels from lower extremity by way of inguinal lymph nodes

Factors involved in lymphatic propulsion

Primary valves Secondary valves Rhythmic contractions of SMC (pacemaker cells)

Chapter 3 - Vessel wall biology Flashcards

(75 cards)