CMG

Chief Function of Cardiovascular System = To transport blood to and from the respiratory system and

the rest of the body

It consists of:

› A four-chambered pump, the heart

› A system to distribute blood from the heart to capillary beds (arteries)

› A system to return blood from capillaries to the heart (veins)

Two main divisions of the circulatory system

› Pulmonary circulation -- conveys deoxygenated blood from the heart to the lungs, where it becomes oxygenated

before returning to the heart

› Systemic circulation -- conveys oxygenated blood from the heart to the body and returns deoxygenated blood to the

heart, which pumps it through the pulmonary circuit for oxygenation

Capillaries are specialized for transfer of oxygen and carbon dioxide, nutrients, and hormones across

their thin walls

Three layers in the walls of structures in the cardiovascular system:

› An inner, tunica intima (called endocardium in heart)

Consists of an endothelium and a thin CT domain

› A middle, tunica media (called myocardium in heart)

Consists of contractile elements, either smooth muscle or cardiac muscle, and CT

› An outer, tunica adventitia (called epicardium in heart)

Consists of CT domains

Thin, simple squamous epithelium

Centrally located flat nucleus

Long axes of cells are oriented parallel to direction of blood flow

Cells joined by:

› Tight junctions (zonulae occludentes) – provides selective permeability

› Zonulae adherentes

› Desmosomes (macula adherens)

Communication via gap junctions

von Willebrand Factor = factor VIII-related antigen

› Found in membrane-bound Weibel-Palade (W) bodies in cytoplasm

› Synthesized by arterial endothelial cells

› Participates in platelet aggregation and adhesion; coagulation

Binds factor VIIIW

Major Property Associated Functions Molecules Involved & Additional Notes

Maintenance of selective

permeability barrier

Passive & Active transport O2, CO2 & Glucose, Electrolytes, Amino Acids,

Pinocytotic vesicles H2O, Small Molecules, Soluble Proteins

Receptor-mediated endocytosis LDL, Cholesterol, Transferrin, Growth Factors

Fenestrations Larger Molecules (diffuse through “holes”)

Control of Thrombosis

Maintenance of

nonthrombogenic barrier

Secretion of antithrombogenic agents

(under NORMAL conditions –

prevents 1o hemostasis)

Prostacyclin (PGl2) – inhibits platelet aggregation

Tissue Plasminogen Activator (TPA) – fibrinolytic

Secretion of anticoagulants (under

NORMAL conditions – prevents 2o

hemostasis)

Thrombomodulin – binds/inhibits thrombin activity inhibits

coagulation cascade

Thrombosis = formation of

clot (thrombus) inside

blood vessel obstructs

flow of blood; Embolus if

breaks free

Secretion of prothrombogenic agents

(after INJURY to vessel wall

Tissue Thromboplastin – initiation of thrombin formation for

coagulation cascade

von Willebrand Factor – platelet aggregation

Plasminogen Activator Inhibitor – promotes fibrin formation

1o hemostasis = platelet aggregation to form a plug at the injury site

2o hemostasis = clotting factors are activated (including thrombin) to form fibrin strands that strengthen the plug

Major Property Associated Functions Molecules Involved & Additional Notes

Modulation of vascular

resistance (BP) (via SM

contraction/ relaxation)

Secretion of

vasoconstrictorsEndothelin, Angiotensin-Converting Enzyme (ACE)

Secretion of

vasodilatorsNitric Oxide (NO), Prostacyclin

Modulation of immune

and inflammatory

responses

Regulation of leukocyte

migration by

expression of adhesion

molecules

Leukocyte Adhesion Molecules & Their Receptors (e.g., Selectins, Integrins,

CD Marker Molecules) [Expressed on luminal surface of endothelium to allow

attachment of lymphocytes, monocytes, and neutrophils → Allows for

diapedesis across vessel wall to surrounding tissues]

Regulate lymphocyte

response and migrationInterleukins

Synthesis and

secretion of hormonal

regulatory factors

Regulation of

hematopoeisisSecretion of growth-stimulating and inhibiting factors

Regulation of blood

pressure

Converts angiotensin I to angiotensin II (vasoconstrictor -- ↑ BP) [Part of the

rennin-angiotensin system]

Inactivate blood-borne

compoundsInactivates norepinephrine, thrombin, prostaglandins, bradykinin, serotonin

Involvement in

lipoprotein metabolism

(oxidation)

Production of free

radicals

LDL, Cholesterol, VLDL are oxidized by free radicals → Oxidized lipoproteins

are endocytosed by macrophages in subendothelial CT → Creates "foam

cells" (1st step of atherosclerotic plaque formation)

Cardiovascular System

Endocardium

Myocardium

Epicardium

Simple squamous epithelium

(endothelium) is

continuous w/ endothelium of

vessels entering & leaving

the heart

Subendocardial layer in

ventricles contain Purkinje fibers

(no subendocardial layer in

papillary muscles & chordae

tendineae)

Concentrically arranged

cardiac muscle cells

Designed to wring blood from the

chambers during systole

(contraction)

Visceral lining of pericardium

made of simple squamous

epithelium (mesothelium)

Thin CT layer contains coronary

vessels, nerves, & autonomic

ganglia. Adipose tissue may be

present to cushion heart within

pericardial cavity.

Endothelium

Subendothelial layer (CT + smooth muscle)

Myocardium

Subendothelial layer

Subendocardial layer

(C.T. unites endocardium and

myocardium; contains

Purkinje fibers)

Myocardium

Atrial Wall

Ventricular Wall

Mesothelium(visceral pericardium)

Autonomic

ganglion cell

(CN X)

Branch of coronary artery

FAT

FAT

Ganglion cells are parasympathetic (vagal) present near the S-A and A-V

nodes in the subendocardial layer innervate coronary vessels and

pacemaker cells

Functions:› Central support structure of the heart

Keeps chambers from collapsing

Supporting structure for valves

› Electrical insulator keeps atrial signal from traveling down to ventricles prematurely

Composition: › Thick, interlaced bundles of collagen fibers with islands of chondroid

(cartilage-like material; calcifies with age)

Three Parts:› Septum membranaceum within interventricular septa

› Annuli fibrosi 4 fibrous rings In arota, pulmonary artery, right & left atrioventricular orifices

Prevent valve-containing outlets from dilating when blood is forced through

› Trigona fibrosa 2 triangular masses (right & left) Connect annuli fibrosi; often contain chondroid

Septum membranaceumwithin upper portion

(membranous part) of

interventricular septum

4 Annuli fibrosi

Cardiac valves regulate unidirectional blood flow in the heart

Atrioventricular valves (L., mitral and R., tricuspid)› Atrial Surface

Composed of sheets of connective tissue on the atrial side (spongiosa) Reinforced with thin, ligamentous strands (fibrosa) which originate at the annuli fibrosi

› Ventricular surface (ventricularis) Contains dense CT, with many layers of elastic fibers

Continuous with the chordae tendineae

› Valves covered by endothelium The 3 layers blend at the free edges of the valves

Aortic and pulmonic valves › Same general structure

› Fibrocartilage plates with accompanying collagenous and elastic fibers located in middle Connected to annuli fibrosi

› Central layer thickening at the middle of the free edges = nodulus Arranti

› Both sides of valves are covered with endothelium

Mitral valve

From: Ross, Kaye & Pawlina Histology A Text and Atlas 4th ed. LWW

Dense CT

Endothelium

Endothelium

from annuli

fibrosi

attach to

chordae

tendineae

Elastic Fibers

loose CTA-V Valves:--Mitral (Left side)

--Tricuspid (Right side)

Cardiac Valves (Cont.)

Sinoatrial node (S-A node) › Location: B/w the right atrium and the superior vena cava

› Composition: A network of interwoven, fine spindle-shaped muscle fibers embedded in connective tissue

› Function: Muscle fiber intrinsic rhythm sets the pace for the entire myocardium Initiates wave of depolarization in the atrial myocytes, causing them

to contract

Atrioventricular node (A-V node) › Location: Posterior lower portion of the interatrial septum

› Composition: Specialized cardiac muscle fibers similar to those of the S-A node

› Function: Receives depolarization signal from atrial myocytes

Atrioventricular bundle (bundle of His)

› Location: Arises from A-V node and extends down within the subendocardial layer to the

interventricular septum Then divides into right and left branches In both ventricles the

branches gradually divide into many thread-like structures which ramify in the myocardium

› Composition: At the A-V node, contains similar cells About halfway down branches, Purkinje

fibers appear

› Function: Purkinje fibers are specialized impulse conducting fibers

Contain relatively few myofibrils but have considerable amounts of glycogen at their central core

Connected to each other by intercalated disks having numerous gap junctions which allow the

depolarizing signal to be passed from cell to cell within the A-V bundle and finally to the ventricular

myocardium

SA and AV pacemaker cells, AV bundle cells• Smaller than normal myocytes

• Conduct impulses 4x faster than cardiac fibers

• Are the only ones that can conduct thru cardiac skeleton

• Coordinate contractions of atria and ventricles

Purkinje fibers

Purkinje fibers

in subendocardial layer

Endocardium

Purkinje fibers

Von Willebrand Disease (VWD)› Most common inherited bleeding disorder

› von Willebrand Factor (Factor VIII-related antigen) = deficient or abnormal In hemophilia, Factor VIII is inactive or missing

› Usually milder than hemophilia

› Affects both males and females vs. hemophilia which mainly affects males

Rheumatic Fever (Valvular Disease)› Inflammation w/ gradual replacement of elastic tissue by collagen,

especially observed in the mitral valve

› Valves lose elasticity HEART MURMUR

› Can also cause pulmonary valve stenosis (narrowing of the pulmonary orifice)

Cardiovascular System: The Heart

This specimen is taken from the top of the left ventricle -- a papillary muscle (pm) anchors a valve via a chorda tendinea (ct)

Endocardium (en)› Simple squamous epithelium (endothelium) at

the lumen

› Thin layer of CT w/ some fibroblasts

Myocardium (my)› Cardiac muscle fibers

Epicardium (ep)› Thicker CT domain

› Infiltrated with adipose tissue

› Blood vessels that dip down into the myocardium to supply oxygenated blood to the myocardium

› An outer mesothelium that is the most superficial part of the visceral pericardium

Endocardium

Myocardium

Endothelium

Mesothelium (most superficial part

of visceral pericardium)

Epicardium

Adipose Tissue

Myocardium

Blood Vessels(supply oxygenated blood to

the myocardium)

Epicardium

Myocardium

Adipose Tissue

This slide shows several large blood vessels (BV) (muscular arteries)› These are branches of the

coronary arteries (supply blood to the heart muscle)

› Occlusion of these vessels by atherosclerotic plaque will result in a heart attack (myocardial infarction)

ID = intercalated discs, sites of intercellular junction between adjacent cardiac myocytes

This specimen has the endocardial

surface of the heart at the bottom

Purkinje fibers (pf)

› Lay just deep to the endocardium (en)

› Part of the cardiac conduction system

› Similar to cardiac myocytes, except

that they have ~2x the diameter

› They have a large amount of

glycogen stored in the sarcoplasm

The unstained glycogen store increases

the volume of the cell and disperses the

myofibrils so that they are less tightly

packed thus, the cytoplasm is less

densely stained

Compare Purkinje fibers to the deeper

myocytes (mc)

Cardiac Myocytes

Purkinje Fibers

Endothelium

This specimen of the heart has some

excellent examples of Purkinje fibers,

located on the endocardial surface of the

heart in a small, oval, lightly stained area

just below the PF label in the thumbnail

image

Notice that Purkinje fibers have the

following characteristics when compared

to standard cardiac myocytes

› More lightly stained

› Have a larger diameter

› Have a few peripheral myofibrils

› A centrally placed nucleus

› A large perinuclear clear area that is

packed full of glycogen granules

Cardiovascular System: The Heart

SEM of a portion of a cardiac muscle fiber. Sarcolemma has been pulled back exposing

the mitochondria (M) and adjacent myofibrils. X5000.

M

TEM, cardiac muscle -- Note single central nucleus in one cell (*), and abundant mitochondria (small arrows). The

myofilaments, though less organized than in skeletal muscle, show distinct striations. T-tubules, invaginations of the

sarcolemma, a component of the diad, occur at the Z-lines in cardiac muscle (solid arrow). The intercalated disc (open arrow) is

clearly seen.

single

central

nucleus

T-tubule

intercalated disc

mitochondria

TEM showing portions of two cardiac muscle fibers joined by an intercalated disc. The disc is composed of numerous

desmosomes (solid arrow) for attachment, and 20A gap junctions (open arrow) for intercellular communication. Components of

the sarcomere include the Z-line (1) in the center of the I-band (2), and an A-band (3), which has a lighter H-band (4) bisected

by an M-line (5). Note the irregular shape of the mitochondria and numerous glycogen inclusions. Rabbit, X42,000.

Gap Junction

Gap Junction Desmosome