THE CIRCULATORY SYSTEM

J u n q u e i r a ’ s B a s i c H i s t o l o g y T e x t & A t l a s 1 5 E d . C h a p t e r 1 1

ENDOTHELIUM
Estimated Total Length of Vessels
• 100,000 – 150,000 km
General Structures of the Circulatory System
• Simple Squamous Epithelium
1. Heart
o propels blood through the system • Lines all internal surface of blood & lymphatic
2. Arteries vessels
o Efferent vessels from the heart Cardiovascular Endothelial Cells
o Become smaller as they branch into the • Special Barrier
various organs o Selectively permeable
o Carry blood to the tissues o Antithrombogenic
3. Capillaries ▪ inhibitory to clot formation
o Smallest vessels • Determine when and where White Blood cells leave
o Sites of O2, CO2, nutrient, and waste the circulation for the Interstitial Space of tissues
product exchange between blood and • Secrete a variety of Paracrine factors for:
tissues o Vessel Dilation
o MICROVASCULAR BED o Constriction
▪ Anastomosing tubules o Growth of adjacent cells
▪ Formed with Capillaries, Arterioles HEART
& Venules Right Ventricle
4. Veins
• Propels blood into PULMONARY circulation
o The convergence of venules into a system
Left Ventricle
of larger channels which continue enlarging
• Propels blood into SYSTEMIC circulation
as they approach the heart
Right Atrium
2 Major Divisions
• Receives blood from the body
1. Pulmonary Circulation
Left Atrium
o Blood goes to lungs for oxygenation
• Receives blood from PULMONARY CIRCULATION
2. Systemic Circulation
o Blood goes through tissues to bring
3 MAJOR LAYERS OF THE HEART
nutrients & remove wastes 1. Endocardium
Lymphatic Vascular System 2. Myocardium
• Lymphatic Capillaries 3. Epicardium
o Thin-walled, closed-ended tubules
o Carry Lymph which merge to form vessels of
steadily increasing size ENDOCARDIUM
Consists of:
• Largest Lymph Vessels • Lining ENDOTHELIUM
o Connect with the blood vascular system • Fibroelastic Connective tissue
o Empty into the large veins near the Heart o With scattered fibers of SMOOTH MUSCLE
▪ Returns fluid from tissue spaces all o Supporting layer
over the body to the blood • Subendocardial Layer
o Deeper layer of connective tissue
o Continuous with Myocardium
o Surrounds the Heart’s Conducting System

MYOCARDIUM
• Thicker in VENTRICLES (particularly in Left)
o As it requires stronger force to pump blood
Contractile Muscle Fibers
• Majority of myocardium
• Arranged SPIRALLY around each heart chamber

EPICARDIUM
• Corresponds to the VISCERAL layer of Pericardium
• Reflected back as the PARIETAL layer of Pericardium
where blood vessels enter & leave the heart
Simple Squamous Mesothelium
• Supported by layer of Loose Connective tissue
o Contains Blood Vessels & Nerves
Adipose Tissue
• Cushions underlying structures during heart
movements
Lubricating Fluid
• Produced by both layers of serous Mesothelial cells
• Prevents friction within Pericardium

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 Parasympathetic Division
CARDIAC SKELETON
• Vagus Nerve
• Dense Irregular Connective tissue
• Slows heartbeat
• Separates the musculature of the Atria from
Sympathetic Division
Ventricles
• Accelerates activity of the Pacemaker
• Forms part of the Interventricular and Interatrial
Afferent Free Nerve Endings
Septa
• Between fibers of Myocardium
• Extends into the Valve Cusps and the CHORDAE
• Register pain (Angina Pectoris)
TENDINEAE
o Where partially occluded coronary arteries
o Where they are attached
cause local oxygen deprivation
Function of Cardiac Skeleton
1. Surrounds, anchors, and supports all heart valves Structural Abnormality of the Valves
2. Provides firm points of insertion for cardiac muscle • Causes
in the atria and ventricles o Scarring from infection
3. Helps coordinate the heartbeat o Hypertension
o Acts as electrical insulation between atria • May not close tightly
and ventricles o Causes slight regurgitation
o Backflow of blood
CONDUCTING SYSTEM OF THE HEART • Produces abnormal heart sound
• Modified cardiac muscle cells o Heart Murmur
• Present in Subendocardial layer and the adjacent • Heart may compensate by working “harder”
Myocardium o Results to enlargement
• Generate and conduct waves of depolarization
o Stimulate rhythmic contractions in adjacent
myocardial fibers
2 Nodes
1. Sinoatrial Node (SA Node)
• Right atrial wall near SVC
• 6-7 mm3 region of less stained cardiac muscle
cells
• Smaller & fewer Myofibrils
• Fewer Intercalated Disks
2. Atrioventricular Node (AV Node)
• Where BUNDLE OF HIS (AV Bundle) emerges
• AV bundle passes through an opening in the
Cardiac Skeleton into Interventricular Septum
o Bifurcates into the LEFT & RIGHT bundles
o Located within Myocardium &
Subendocardial Layer
o Further subdivides into PURKINJE FIBERS at
the Apex
Purkinje Fibers
• Pale-staining fibers
• Larger than the adjacent contractile fibers
• Sparse, peripheral Myofibrils, and much Glycogen
• Trigger waves of contraction through both Ventricles
simultaneously
Innervation of the Heart
• Parasympathetic and Sympathetic
• Ganglionic Nerve Cells & Fibers
o Present in the regions close to SA & AV
node
o Affect HR & rhythm

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 VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF)
• Stimulates VASCULOGENESIS
o Formation of vasculature from
EMBRYONINC MESENCHYME
• Promote ANGIOGENESIS
o Capillary sprouting & outgrowth from small
existing vessels

ANGIOPOIETINS
• stimulate endothelial cells to recruit Smooth Muscle
cells and Fibroblasts to form the other tissues of the
vascular wall

Thrombus
• An intravascular clot with Fibrin framework that
forms when endothelial cells are damaged
• In endothelial tissue injury, collagen is exposed in
the subendothelial tissues and induces blood
platelets aggregation
• Platelets release factors which initiate a cascade
of events that produce FIBRIN from circulating
Plasma Fibrinogen
Emboli
TISSUES OF THE VASCULAR WALL • Solid masses that detach from large Thrombi
• Carried by blood and causes obstruction of
Smooth Muscle & Connective Tissue
vessels
• ABSENT IN CAPILLARIES
Tissue Plasminogen Activator (tPA)
• Present in all other vessels in addition to
• Serine Protease that break down Fibrin and
Endothelium
quickly dissolves clot
• Factors affecting its arrangement:
• Used to treat MI & Pulmonary Embolism
o Mechanical factors
▪ Blood pressure
o Metabolic factors SMOOTH MUSCLE FIBERS
▪ Reflects the local need of tissues • Present in the walls of all vessels larger than
Capillaries
ENDOTHELIUM • Arranged HELICALLY in layers
• Specialized Simple Squamous Epithelium • Arterioles & Small Arteries
o Polygonal o Connected by Gap Junctions that permits
o Elongated with long axis in the direction of ▪ Vasodilation
blood flow ▪ Vasoconstriction
• Acts as a semipermeable barrier between the BLOOD
& INTERSTITIAL TISSUE FLUID CONNECTIVE TISSUE
Other Endothelial Functions • Present in vascular walls in variable amounts
1. Nonthrombogenic Surface o Based on local function requirements
o Secretes agents that control local clot Collagen Fibers
formation • Present in:
▪ Heparin o Subendothelial layer
▪ Tissue plasminogen activator ▪ Between smooth muscle layers
▪ Von Willebrand factor o Outer covering
2. Vascular tone & Blood flow regulation Elastic Fibers
o Secretes factors that stimulate muscle • Provide resiliency to expand under pressure
contraction • Forms PARALLEL LAMELLAE in Large Arteries
▪ Endothelin-1 o Regularly distributed between muscle layers
▪ Angiotensin-converting enzyme Ground Substance
(ACE) • Variations in amount & composition contribute to
o Secretes factors of relaxation (including the Physical & Metabolic properties of the wall
▪ Nitric oxide (NO) o Especially their PERMEABILITY
▪ Prostacyclin • Proteoglycans
3. Inflammation & Local immune responses • Hyaluronate
o Specific WBCs undergo Transendothelial 3 CONCENTRIC LAYERS OF LARGE VESSELS
migration at sites of injury/infection
1. Tunica Intima
o Interleukins
2. Tunica Media
o P-selectin
3. Adventitia / Tunica Externa
▪ Expressed rapidly in the presence
of Weibel-Palade Bodies
4. Growth Factors
o Secreted under various conditions
o VEGF
o Angiopoietins

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 TUNICA INTIMA
Consists of:
• Endothelium
• Thin Subendothelial layer of Loose CT
• Arteries
o Internal Elastic Lamina is present
▪ a thin layer of elastin
▪ has holes allowing better diffusion
of substances from blood deeper
into the wall

TUNICA MEDIA
• Concentric layers of helically arrange Smooth Muscle
cells
• Interposed between the muscle fibers (produced by
Smooth Muscle cells)
o Elastic Lamellae
o Reticular fibers
o Proteoglycan
• Arteries
o External Elastic Lamina may be present
▪ Separates media from outermost
tunic

ADVENTITIA / TUNICA EXTERNA

Connective tissue consisting mainly of:
• Type 1 collagen
• Elastic Fibers
• Continuous with and bound to the Stroma of organ
o Where blood vessel runs
Large Vessels
• Contains network of VASOMOTOR NERVES
o Unmyelinated Autonomic Nerve Fibers
o Releases NOREPINEPHRINE
(Vasoconstrictor)
o More in ARTERIES

VASA VASORUM
• “Vessels of vessels”
• Present in Adventitia of large vessels
• Since wall of larger vessels is too thick to be
nourished solely by diffusion
• Consists of Arterioles, Capillaries, & Venules that
provide metabolites to cells far from lumen
• More in VEINS
o Since they carry deoxygenated blood

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VASCULATURE ARTERIAL SENSORY STRUCTURES

CAROTID SINUSES
ELASTIC ARTERIES • slight dilations of bilateral Internal Carotid Arteries
1. Aorta • Act as BARORECEPTORS
• ~50 elastic lamellae o Monitors BP
o More in Hypertensive • Tunica Media is THINNER
2. Pulmonary Artery o Allows greater distension when BP rises
3. Their largest branches • Adventitia
• Also called CONDUCTING ARTERIES o Contains many sensory nerve endings from
o Major role is to carry blood to smaller CN IX (Glossopharyngeal Nerve)
arteries Carotid Bodies
• Present in walls of Carotid Sinuses
THICK TUNICA MEDIA
Aortic Bodies
• Most prominent feature
• Present in walls of Aortic Arch
• Elastic Lamellae alternate with features of Smooth
• Transmits signal to CN X (Vagus Nerve)
muscle
Chemoreceptors
Elastic Laminae
• Monitors blood CO2, O2, & pH
• important function of making the blood flow more
• Found in Carotid & Aortic Bodies
uniform
• Elastin rebounds passively after the Arterial wall is PARAGANGLIA
stretched by the high pressure of Ventricular Autonomic Nervous System that includes:
contraction (Systole) • Baroreceptors of Carotid & Aortic bodies
o Passive rebound helps • Chemoreceptors of Carotid & Aortic bodies
▪ maintain arterial pressure when • Rich capillaries
Ventricles relax (Diastole)
• Glomus Cells
▪ continue blood flow away from the
o Derived from Neural crest
heart
o Surrounds the capillaries
o Filled with dense-core vesicles containing
TUNICA INTIMA
• Many smooth muscle cells in the Subendothelial ▪ Dopamine
▪ Acetylcholine
Connective Tissue
▪ Other neurotransmitters
• shows folds in cross-section
o Supported by Satellite Cells
o due to loss of BP & contraction at death
• Ion channels respond to stimuli in Arterial blood
Internal Elastic Lamina
o Hypoxia (low O2)
• between Intima & Media
o Hypercapnia (excess CO2)
• more defined than Elastic Lamina of Media
o Acidosis
ADVENTITIA • Glossopharyngeal Nerve
• much thinner than Media o Forms synapses with Glomus cells
o Signal the brain centers to initiate CV &
respiratory response
Atherosclerosis
• Disease of elastic arteries & large muscular
arteries
• Initiated by damaged Endothelial Cells oxidizing
LDLs in the Tunica Intima
• Induces adhesion and Intima entry of
Monocytes/Macrophages to remove the
modified LDL forming FOAM CELLS (Lipid-filled
macrophages)
• FATTY STREAKS form from accumulated Foam
cells and free LDL
• ATHEROMAS (fibro-fatty plaques) consisting of a
gruel-like mix of Smooth Muscle cells, Collagen
fibers, and Lymphocytes with necrotic regions of
Lipid, Debris, and Foam cells
o Weakens walls of Elastic Arteries causing
ANEURYSMS
o Can occlude Muscular Arteries
(Coronary)
• Risk Factors
o Dyslipidemia
o Hyperglycemia
o HPN
o Smoking

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MUSCULAR ARTERIES • Muscle tone normally keeps Arterioles closed
o Resists blood flow
• Distributing arteries
• Major determinants of Systemic BP
• Help regulate BP
•
o contraction or relaxation of Smooth muscle
in Media

INTIMA
• Has thin Subendothelial Layer
• Prominent Internal Elastic Lamina

MEDIA
• ~40 layers of Smooth muscle cells
o Interspersed with variable number of Elastic
Lamellae (depends on size of vessel)
• External Elastic Lamina
o Present only in larger Muscular arteries

ADVENTITIA
Connective tissue contains:
• Lymphatic Capillaries
• Vasa Vasorum
• Nerves
May penetrate to the outer part of Media

ARTERIOLES
• Smallest arterial branch
• Only has 1-2 Smooth muscle layers
• Indicates beginning of an organ’s Microvasculature
• <0.1 mm diameter
• Lumens as wide as the wall
• Subendothelial Layer = thin
• Elastic Lamina = absent
• Media = circularly arranged smooth muscle cells
• Adventitia = thin & inconspicuous
• Almost always branch to form Anastomosis
• Smooth muscle fibers act as Sphincters at the end

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 CAPILLARY BEDS
• Permit & regulate metabolic exchange blood &
tissue
• Network of the smallest blood vessels
• Density is dependent on the metabolic activity of the
tissues
o High metabolic activity=abundant Cap. beds
▪ Kidney
▪ Liver
▪ Cardiac & skeletal muscle
o Low metabolic activity
▪ Smooth muscle
ARTERIOVENOUS SHUNT
▪ Dense connective tissue
• Arteriovenous Anastomosis
Metarterioles
o Arterioles can bypass capillary networks
• 1-2 supplies capillary bed
and connect directly to Venules
• Thoroughfare Channels
o Thicker Media & Adventitia
o Continuous with Metarterioles
o Richly innervated with Sympathetic &
o Lacks smooth muscle
Parasympathetic nerve fibers
o Connects with Postcapillary Venules
o Vasoconstriction regulates blood flow
o High capillary BF = greater heat release • Precapillary Sphincters
o Metarteriole muscle cells that control blood
VENOUS PORTAL SYSTEM flow into Capillaries
• Blood flows through 2 successive capillary beds o Contract & relax cyclically
separated by a Portal Vein ▪ 5-10 cycles/min
• Allows efficient delivery of Hormones/nutrients ▪ Causes pulsatile blood flow
picked up from the 1st Capillary network to cells
CAPILLARIES
around the 2nd Capillary bed
• Simple layer of Endothelial cells
• Hepatic Portal System
• Encircled by scattered Smooth muscle cells
• Hypothalamic-Hypophyseal Portal System
• Converge into the Thoroughfare Channels
o Anterior Pituitary Gland
• Diameter = 4-10 μm
ARTERIAL PORTAL SYSTEM • Length = ≤ 50 μm (total = ~> 100,000 km)
• Kidney • Thickness = 0.25 μm
• Afferent arteriole → capillaries → efferent arteriole • Total surface area = 5000 m2
• 90% of the body’s vasculature
• Most are empty at any given time
o Due to the cyclical opening of sphincters
• Optimizes exchange of water & solutes
o Diffusion
o Transcytosis
• Nuclei
• Curved to accommodate its size

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3 HISTOLOGIC TYPES OF CAPILLARIES
1. Continuous Capillaries
2. Fenestrated Capillaries
3. Discontinuous Capillaries/Sinusoids

CONTINUOUS CAPILLARIES
• Most common
• Many Occluding Junctions
• Location:
o Muscle
o Connective tissue
o Lungs
o Exocrine glands
o Nervous tissue
• Important in maintaining the endothelial Blood-Brain
FENESTRATED CAPILLARIES Barrier in CNS
• Allows more extensive molecular exchange • Proliferate & differentiate into Smooth muscle in
• Endothelial cells have Fenestrations (~80nm) vessels after injuries
• Basement membrane is continuous
• Location: organs with rapid interchange Diabetic Microangiopathy
o Kidneys • Diffuse thickening of the Capillary Basal Laminae
o Intestine caused by Hyperglycemia
o Choroid plexus (produces CSF) • Decreases metabolic exchange of these vessels
o Endocrine glands o Kidneys
o Retina
SINUSOIDS o Skeletal Muscle
• Permits maximal exchange of MACROMOLECULES o Skin
• Discontinuous layer with spaces between & through
cells
• Highly discontinuous Basement Membranes
• Larger diameters (30-40 μm)
o Slows blood flow
• Location:
o Liver
o Spleen
o Bone Marrow
o Some Endocrine
Pericytes
• Mesenchymal cells with long cytoplasmic processes
• Partly surrounds the endothelial layer
• Secrete many ECM components
• Form their own Basal Lamina
o Fuses with the Basement Membrane of
endothelial cells
• Contributes in dilation/constriction of capillaries
o Indicated by the presence of Cytoskeletal
networks of Myosin, Actin, & Troponin

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VENULES
• Large Lumen diameter compared to its thin wall
o Characteristic of ALL venules
Postcapillary Venules
• Have larger Pericytes (15-20 μm)
• Primary site where WBCs adhere to
Endothelium & leave the circulation at sites of
infection or tissue damage
• Converge into larger Collecting Venules
• Junctions between Endothelial cells are the
LOOSEST of microvasculature
o Migration of leukocytes during
inflammation
o Loss of fluid during inflammatory
response (Edema)
Collecting Venules
• Have more distinct contractile cells
• Muscular Venules
o 2-3 layers of Smooth muscle
o Starts to surround the venules as the
size increases
VEINS
• Blood has low BP
• Blood moves toward heart through:
o Smooth muscle contraction in the
Media
o External compression from
surrounding Skeletal muscles & organs
Classified either as:
1. Small veins
2. Medium veins
• Most are Small/Medium (≤ 10mm)
o located close & parallel to Muscular
Arteries
o Intima = thin
o Media has small bundles of Smooth
muscle cells + Reticular + Elastic fibers
o Adventitia = thick & well developed
3. Large veins
• Paired with Elastic Arteries close to the
heart
• Intima = well-developed
• Media = thin
o with alternating Smooth muscle &
connective tissue
o with Elastic fibers
• Adventitia = thicker than media
o Often has longitudinal bundles of
Smooth muscle
o with Elastic fibers
• Internal Elastic Lamina = may be present

VALVES
• Important features of Large & Medium veins
• Thin paired folds of INTIMA
• Projects across the lumen
• Rich in Elastic fibers
• Endothelium covers both sides
• Numerous in Legs
• Prevents backflow of blood

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 • Valves
LYMPHATIC VASCULAR SYSTEM o Forms in specific domains of adjacent
endothelial cells where there is no
Hemidesmosome connecting to the Basal
LYMPHATIC CAPILLARIES
Lamina
• Collect Lymphs
o Facilitates entry of fluid
o Excess interstitial fluid
o Prevents backflow
o Does not contain RBCs
o Enters Lymphatic capillaries by: LYMPHATIC VESSELS
▪ Flowing between endothelial cells • Convergence of the smaller Lymphatic Capillaries
▪ Transcytosis
• Thin walls
• Present in most tissue with blood microvasculature
• Increasing amounts of CT & Smooth muscle
o Except in
o Does not form clear distinct outer tunics
▪ Bone marrow
• Valves = present
▪ Most of CNS
o Comprised of complete Intimal Folds
• Tubes of very thin endothelial cells
(similar to veins)
• Lack Tight Junctions
• Lymph flow is controlled like in Veins
• Basal Lamina = discontinuous o Valves
o Has fine anchoring filaments of collagen o External forces (muscle contractions)
that extends to surrounding CT preventing
• Major distributor of Lymphocytes, antibodies, &
its collapse
other immune components
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LYMPH NODES
• Site where Lymph is processed by cells of Immune
system

2 LARGE TRUNKS OF LYMPHATIC VESSELS

1. Thoracic Duct
2. Right Lymphatic Duct
• Where the lymphatic vessels ultimately converge &
through which Lymph empty back into blood
• Similar structure with Small Veins
• Adventitia = underdeveloped but contains
o Vasa Vasorum
o Neural network

THORACIC DUCT
• Enters circulatory system near the junction between
o Left Internal Jugular Vein
o Left Subclavian Vein

RIGHT LYMPHATIC DUCT

• Enters circulatory system near confluence between
o Right Subclavian Vein
o Right Internal Jugular Vein

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