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Vasculogenesis

blood vessels arise from coalescence of hemangioblasts, which arise from blood islands

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Angiogenesis

vessel formation via branches arising from existing vessels

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How do major vessels form?

Vasculogenesis

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Why is it important to understand the processes of angiogenesis and vasculogenesis?

An understanding of these processes is relevant to developing therapeutic strategies to produce revascularization of ischemic tissues or inhibit angiogenesis in cancer and other disorders

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When and where does early vasculogenesis begin?

In week 3 in extraembryonic splanchnic mesoderm surrounding the yolk sac: formation then moves into lateral plate mesoderm

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What is the first site of formation of blood islands

Yolk sac.
Islands arise from mesoderm cells that are induced to form hemangioblasts, a common precursor for vessel and blood cell formation

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Hemangioblasts differentiate into what two populations of cells

angioblasts and hematapoetic stem cells

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Define angioblasts

vascular precursors - form endothelial cells. coalesce into cords and form a lumen

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Define hematapoietic stem cells

differentiate into all types of blood cells

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mesenchymal cells to hemangioblasts is regulated by

FGF 2

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What factor elicits regional change in blood islands

VEGF (vascular endothelial growth factor)
signal to express VEG F may invlove HOXB5 which upregulates VEGF receptor FLK1

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Factors involved in angiogenesis

VEGF, Ang1, Ang2

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Role of Ang1

in angiogenesis, recruits pericytes to sm muscle cells in large vessels to organize mature blood vessels

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Role of Ang 2

works where you might want to punch a hole and have something grow out. works on endothelial cells and stops interactions btwn them - either absence of growth OR cell death.

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Vein specific genes controlling venous development

EPHB4

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master gene for lymphatic vessel differentiation

PROX1

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Specification of vessel type happens when?

Soon after angioblast induction

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What factors specify arterial development?

SHH from notochord induces expression of VEG-F in mesoderm
VEG-F induces Notch pathway which specifies arterial development
through expression of EphrinB2 (ligand)

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AGM stands for?

Aorta - gonad - mesonephros region.

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What is found in the AGM

Definitive hematopoietic stem cells. These cells will eventually colonize the liver, which becomes major hematopoietic organ of the embryo (2-7 months). Hematopoiesis moves form liver to bone marrow at 7 months.

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Progression of hematopoeisis

Blood islands - FGF@ tells them to become hemangioblasts - difinitive hematopoeitic stem cells then seen in AGM - liver - bone marrow.

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What is a Hemangioma

Abnormally dense collection of capillary vessels. common tumors of infancy. focal or diffuse, look for other secondary complications

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What is a Port Wine Stain?

superficial and dilated capillaries in the skin.

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Tumor Angiogenesis

When some of the tumor cells switch to an angiogenic phenotype, the local equilibrium between positive and negative angiogenic refulators changes. allows the tumor to grow.

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Folded endothelial tube whose wall is thickened to act as a regulated pump

Heart

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Endocardium

consisting of an endothelial lining and sub endothelial CT

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Myocardium

Functional syncytium of striated cardiac muscle fibers foming 3 major types of cardiac muscle

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3 major types of cardiac muscle

atrial muscle
ventricular muscle
specialized excitatory and conductive muscle fibers.

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Epicardium

Visceral layer of the pericardium
is a low friction surface
lined by a mesothelium in contact with the parietal pericardial space.

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Cardiomyocytes (3 kinds)

Contractile
myoendocrine
Nodal

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Contractile cardiomyocytes

Contract to move blood

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Myoendocrine cardiomyocytes

produce atrial natriuretic factor that stimulates diuresis and excretion of Na in urine by +glomerular filtration rate, -blood volume

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Nodal Cardiomyocytes

Specialized to regulate contraction of the heart
SA and AV node

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Characteristics of cardiac muscle

striated, branched, uninucleate cells connected to e/o by intercalated discs

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Intercalated disc junction types (3)

Fascia adherins
macula adherins
gap junctions

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Fascia adherins

anchoring sites for actin. connect to closest sarcomere

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macula adherins (desmosomes)

stop separation during contraction by binding intermediate filaments, joining cells together.

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Gap junctions

allow potentials to spread between cardiac cells by permitting the passage of ions btwn cells, producing depolarization of heart muscle

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Electrical conduction system pathway of Heart

SA node --> AV node --> bundle of his (sends out)--> L and R bundle branches --> purkinje fibers

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Specialized muscle cells that conduct electrical impulses

purkinje fibers.

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How can purkinje fibers be distinguised from myocardium?

by size (much larger) and by their staining (lighter, full of glycogen)
but they do have some of the other features of cardiac myocytes, including centrally located nubleus and intercalated disc.

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Vessel that ensures continued flow through capillaries during cardiac diastole

arteries.

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3 major organizational levels or tunics of arteries

tunica intima,
tunica media
tunica externa

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Tunica externa/adventitia (location, composition function)

outermost layer of blood vessel wall
composed of loose CT, elastic and collagen fibers
helps anchor vessel to other tissues

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external elastic lamina that separates the tunica media from tunica externa

vaso vasorum

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Tunica media (location composition fxn)

middle layer of vessel wall
composed of circularly arranged layers of sm m cells.
responds to autonomic innervation (vasoconstriction/vasodilation)

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Tunica intima/ interna (location, composition function)

innermost layer of blood vessel wall
composed of an endothelium and subendothelial layer, external layer of elastic fibers, the internal elastic lamina

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Three major groups of arteries

large elastic arteries
medium sized muscular arteries
small arteries and arterioles

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Type of artery that 1. receives blood from heart under high pressure and 2. keeps blood circulating continuously while the heart is pumping intermittently

Large elastic (conducting) arteries
distend during systole and recoli during diastole

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Examples of large elastic arteries

the aorta, and its largest branches (brachicephalic, common carotid, subclavian, common iliac)

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Large amounts fo fenestrated elastic sheaths are found in the tunica media with bundles of smooth muscle cells permeating the narrow gaps between elastic lamella in this type of artery...

large elastic artery

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Blood vessels, nerves and lymphatics can be recognized in the tunica adventitia of what type of artery

large elastic arteries.

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What does vasa vasorum and nervi vasorum mean?

The blood vessels and nerves to the vasculature.

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What type or artery allows a selective distribution of blood to different organs in response to functional needs?

Muscular distributing arteries

note that we see significant reduction in elastic components and an + in sm m fibers compared to large elastic arteries

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examples of muscular (distributing) arteries

radial, tibial, popliteal, axillary, splenic, mesenteric, intercostal

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What are the layers of the tunica intima of muscular arteries

endothelium
sub endothelium
internal elastic lamina

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The final branches of the arterial system, which regulate the distribution of blood to different capillary beds by vasoconstriction/ vasodilation are called?

arterioles.

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Arterioles are regarded as

resistance vessels and are the major determinants of systemic BP
partial contraction of vascular sm m. exists (TONE)

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What is the microcirculation composed of

Terminal arteriole, capillary bed, adn postcapillary venules.

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What is the functional unit of the cardiovascular system

capillaries.
smallest blood vessels. connect arterioles to venules.
contain only the tunica intima; vasment membrane and endothelium only.

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Continuous capillaries

lined by endothelium with tight junctions and a basal lamina with pericytes

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fenestrated capillaries

have pores or fenestrate (GI, Kidney)

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sinusoids, or discontinuous capillaries

characterized by an incomplete endothelial lining and basla lamina, with gaps or holes between and within endothelial cells
liver, spleen

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What type of vessel is the capacitance (reservoir) vessel

veins

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preferred site of migration of blood cells into the tissues(diapedesis)?

post capillary venules.

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Characteristics of veins.

thin walled. High capacitance attibutable to distensibility of their wall (compliance vessels)
contain large amount of the blood volume.
also contain tunics, not as defined
VALVES, to prevent reflux of blood

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Vessels responsible for transport of chylomicrons, (lipid containing particles), remove excess fluid from intersitital spaces, and conduct immune cells...

lymphatic vessels.

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Two types of Lymphatic drainage

Intrinsic contraction (when vessle become expanded by lymph)
Extrinsic contraction (external factors such as contraction of muscle compresses the lymph vessel)

both lead to pumping of lymph.

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result when lymph drainage impaired

edema

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Lymphedema

caused by a defect in the transport of lymph bc of abnormal vessel development or damaged lymphatic vessels

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Filaviasis (elephantitis)

parasitic infection of lymph vessels by worms
transmitted by mosquito bites
causes damage to lymphativ vessels --> chronic lymphedema of legs and genitals

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Chylothroax or Chylous ascitis

accumulation of high fat containing fluid (chyle) in abodmen or thorax
result of trauma, obstuction, abnormal development of lymphatic vessels.

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Endothelial cells produce what to regulate blood flow

vasoactive substances (NO, prostacyclin, endothelin 1)

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NO and Prostacyclin functions

Relaxation of Sm m.
vasodilation
IN BLOOD VESSELS.
produced by endothelial cells.
(prostacyclin also prevents platelet adhesion and clumping leading to blood clotting)

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Function of endothelin 1

potent vasoconstrictor peptide

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Aside from vasoconstriction/vasodilation, endothelial cells also play a role in what two processes?

Homing and inflammation

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How does the permeability of capillary endothelial cells vary?

It is tissue specific.
also topographic - endothelial cells at venous end are more permeable than those at arterial end.

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In atherosclerosis, what layer do plaques deposit in?

Tunica intima

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what types of vessels do we see atherosclerosis in?

arteries sustaining High BP.

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Atherosclerosis is no recognized as a chronic __________ disease. also correlates with serum levels of what

imflammatory.
high levels of cholesterol or LDL

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what is familial hypercholesterolemia?

A genetic defect in lipoportein metabolism, associates with atheroslcerosis and MI before patients reach 20 years of age.