Circulatory system consists of Two systems:

Cardiovascular system (CVS): blood circulates (closed system)

Lymphatic system for lymph flow (open system)

Common structural features: MACROSCOPIC HOLLOW organs + fluid in lumen

Three layers around the lumen: Why? Push fluid forward!
• Tunica intima (endothelium + BM + connective tissue), same in all vessels
• Tunica media: muscle layer (pushes fluid forward), Variations
• Tunica externa or adventitia: connective tissue, same in all vessels
Tunica media exhibits the greatest variations and used for classification
*SOLID organs’ terminology: cortex + medulla (Latin: bark + middle)
*MiCROSCOPIC HOLLOW organs: 1 layer, only tunica intima or less, why? For diffusion!

Dr Anikở Szabở MD, PhD

BM: basement membrane
 Functions of CVS

1 It pushes blood, always in one directions: forward!

Clinical: Backward movement of any fluid is patho-physiology!
2 Oxygen/ CO2 and nutrients/ wastes transport and exchange
3 Temperature homeostasis
4 Transport and delivery of hormone
5 Transport and delivery of immune cells
 Objectives

1. Describe the structure, function, location and diseases of pericardium

2. Describe the structure, function, location and diseases of myocardium
3. Describe the structure, function, location and diseases of endocardium
4. Describe the structure, function, location and diseases of Purkinje fibers
 Etymology of the Components of CVS

Hollow organs Blood in the lumen is a fluid connective tissue

Heart Vessel Blood
Cardia (Greek) Angio- (Greek) Hemo-, hemat-, hemato- (Greek)
Cor (Latin) Vas- (Latin) Sanguine (Latin)

Sacré Coeur de Montmartre

 Definitions

Cardiac muscle cell = cardiomyocyte

Cardiac muscle fiber = cardiomyocytes joined by intercalated discs, end to end
Cardiac muscle tissue = two or more cardiomyocytes

Morphological Syncytium: a long, multinuclear cell made by fusion of uninuclear cells

• Example: skeletal muscle

Physiological Syncytium: cells interconnected by specialized plasma membranes with gap

junctions, and are synchronized electrically in an action potential
• Example: cardiac muscle, some smooth muscle

Greek: syn-"together" and kytos “cell")

Extracellular fluids (ECF) are named by locations

1 Two fluid-connective tissues:

• Lymph: ECF in lymphatic vessel
• Blood plasma: ECF in blood vessel
2 Interstitial fluid or ground substance:
• ECF between vessels and cells
 Histology of the Heart

The heart is a muscular pump that maintains unidirectional flow of blood

 Heart of a mouse
1 Myocardium of left ventricle
2 Lumen of left ventricle
3 Myocardium of Interventricular septum
4 Lumen of right ventricle
5 Myocardium of right ventricle
6 Papillary muscle in left ventricle

3 6
4
5
 3 layers of the heart from outside

2 1

3 Observe!
Blue mesothelium + pink endothelium are both:
• simple squamous epithelium
 Outside Layer:
• Serous Pericardium or Tunica externa of heart
• Two layers: parietal + visceral (=epicardium) + fluid

Histology
• Mesothelium + BM + areolar CT + adipose tissue
Function:
• Lubrication for pumping
• Epicardium: coronary vessels (blood supply) of myocardium and sympathetic
autonomic nerve supply of coronary vessels are located under epicardium
• Reminder from MSK: muscle needs both blood and action potential to “live”
Location: outside layer of heart
 Serous Pericardium, a serous membrane (serosa)
Structure: “Water balloon” with two walls + cavity between + fluid in cavity* (15-50 ml)
• Wall 1: Epicardium = Visceral pericardium, “glued” to myocardium
• Wall 2: Parietal pericardium, “glued” to fibrous pericardium
• Between the two walls: pericardial cavity (lumen) + pericardial fluid
• Histology: mesothelium + BM + areolar connective tissue + adipose CT
Function:
• Lubrication for smooth “pumping” or contraction (by slippery, non-adhesive surfaces)
Etymology: peri=around, cardia=heart, epi=top, viscera=organ, parietal=wall, myo=muscle
Hilus Reflections
Epicardium:
Hilus Reflections
No serosa; Visceral pericardium
“Gate” for becomes
Macroscopic *
parietal pericardium
* and vica versa
• Vessels * *
*
• Nerves Water
*
*
• Lymphatics *
 Epicardium or Visceral pericardium
Mesothelium (M) = simple squamous epithelium (flat nucleus) (Facing pericardial lumen)
• Function: Formation of “slippery” pericardial fluid + Phagocytosis/ Antigen presenting cell
Sub-mesothelial Connective tissue (CT): Areolar CT (loose irregular) + adipose (A) CT
• Function:
• Keeps mesothelium and myocardium alive
• Coronary vessels + extrinsic autonomic nerves + lymphatics are buried in adipose tissue that
supply the myocardium (blood supply to cardiac muscle from outside to inside)
* M
* * * PF
F
A M=Mesothelium
PF=pericardial fluid
CT= connective tissue
F=fibro-elastic CT
Ep=epicardium
Myo=myocardium
A=adipose tissue
Co=coronary artery
yo
N=autonomic nerve
 Epicardium
1 Lumen of a ventricle A Lumen of pericardial cavity
2 Endocardium B Mesothelium (flat nucleus)
3 Myocardium C Submesothelial connective tissue: areolar
4 Epicardium D Adipose tissue in submesothelial connective tissue
E Myocardium
Chunk of heart
1 E
2

D Coronary artery
3 Coronary vein

4
C
A B
 Diseases of Pericardium

1 Pericarditis (infection)

2 Cardiac tamponade
(too much pericardial fluid blocks blood flow through the heart)

3 Mesothelioma
(malignant cancer of mesothelium)
Middle Layer:
• Myocardium or Tunica media of heart

Histology (structure):
• Cardiac muscle tissue
Function:
• Conducts action potential by gap junctions
• Contracts and pumps blood
Location:
• Middle layer of heart
 Cardiac muscle tissue in myocardium
3 cardiac m cells 1 Intercalated discs = cell junctions between cardiac muscle cell
2 Branching of cardiac muscle cells
3 Striations (alternating A bands and I bands)
4 Uni- or binucleation in the center of cardiac muscle cell
5 Endomysium: fibroblasts + collagen
6 Endomysial capillaries: endothelium + erythrocytes
1
2 4
3
1
2

1 6
3
5
 Cardiac muscle tissue in myocardium
3 cardiac m cells 1 Intercalated discs = cell junctions between cardiac muscle cell
2 Branching of cardiac muscle cells
3 Striations
4 Uni- or binucleation in the center of cardiac muscle cell
5 Endomysium: fibroblasts + collagen
6 Endomysial capillaries: endothelium + erythrocytes
 Electron Microscopy of two cardiac muscle cells
1 Intercalated disc (ICD)
2 Z disc
3 Thin-actin filament proteins in I band
4 Thick-myosin filament proteins (H zone/M line in A band)
5 Mitochondria, between the myofibrils

ICD is a densely stained line Electron Microscopy 50 000x: ICD is staircase-like

5 1 5

1 4 3
Cell 1 Cell 2
1 2
5
Light Microscopy 400x
4 3
2 Cell 1 1 Cell 2
 Intercalated disc (ICD)
Remember 4 structures!

Intercalated disc (ICD) =

1 Two interdigitating sarcolemmas between two cardiomyocytes, in a shape of a stair-case
 ICD contains cell-to-cell junctions to keep the tissue together during pumping
• 2 Fascia adherens (adhering junction)
• 3 Macula adherens (desmosome)
 ICD also contains gap junctions, to spread action potential, making cardiac muscle
fibers a physiological syncytium (= Greek: together cells)
• 4 Gap junction (communicating junction, nexus)
 Diseases of Myocardium
1 Cardiac muscle disease
Infection: myocarditis (rheumatic fever)
2 Blood vessel disease
Coronary artery is obstructed:
• Cardiac muscle tissue is injured (angina: chest pain)
• Cardiac muscle tissue is dead (heart attack or myocardial infarct)
3 Conduction system disease
Action potential disruption leads to
• arrhythmias
• heart blocks
• cardiac arrest
• sudden death
 Injury and Repair of Cardiac Muscle

Myocardial Infarct (MI)

Injured cardiac muscle tissue dies and is replaced by collagen (fibrous connective tissue)
Loss of function of pumping based on the size of the injury

Diagnosis:
Injured cardiac muscle cells leak subunits of TnI and TnT into blood, in 3-12 hours
Measurement of these proteins are diagnostic markers of MI

Prognosis: cardiac muscle does not regenerate or very minimal

Recovery of the person depends on the size of the injury of the left ventricle
 Inside Layer:
• Endocardium or Tunica interna/intima of heart

Histology (structure):
• Endothelium + BM + areolar CT
• (Endothelium = simple squamous epithelium (flat nucleus) (Facing
lumen of heart chambers)
Function:
• “Slippery” blood-heart barrier
• Covers valves
• Sub-endocardium: Intrinsic nervous system of heart (Purkinje fibers)
Location:
• Inside layer of heart
• Covers valves
 Valves of Heart: Avascular structures: Keep blood flow in one direction, no backflow
Two Structures of valves
1 Leaflets of Fibro-elastic tissue 2 Chordae tendineae (A-V valves only)
• Fibro-elastic sheet in center (F) • Fibrous thread-like cords (collagen)
• Covered by endothelium on both sides (E) • Covered by endothelium
• Myocardium (M), edge of valve • Attach to papillary muscles:
• Prevent A-V valves to open into atria on systole

Mitra
Leaflet, no chordae tendineae
 When you study endocardium, remember Purkinje fibers, running immediately under the
endocardium, before penetrating myocardium

Structure:
Non-contractile, specialized, cardiac muscle cells (pacemaker or autorhythmic cardiomyocytes)
Function:
1 Autorhythmicity: creating action potential (AP)
2 Conducting AP: Terminal branches of Conduction system or “Intrinsic Nervous system” of
heart to give action potential to papillary muscles and ventricular myocardium
Action potential invades myocardium from inside (endocardium)
Location: subendocardium connective tissue

https://www.youtube.com/watch?v=RYZ4daFwMa8
Animation about Conduction system
Flow of cardiac action potential in Conduction system or “Intrinsic Nervous system” of heart
Anatomy Electric insulation Atrial syncytium
between atrias and ventricles ↓
By fibrous skeleton; (yellow) Fibrous skeleton (yellow)
only bundle of His can cross it. ↓
Ventricular syncytium
Flow of cardiac action potential in Conduction system or “Intrinsic Nervous system” of heart
Name Location: Sub-endocardium Beat/min:Heart Rate
Sino-atrial (SA) node Right atrium 60-100 beat/min
Physiology True pacemaker At Junction of superior vena cava; • Autorhythmic
↓ AP is generated and spread to atrial
Atrial syncytium syncytium 1st

Atrio-ventricular node In interatrial septum near the 40-60 beat/min

(AV node) opening of the coronary sinus, • Autorhythmic
Dormant pacemaker Above tricuspid valve
↓ Simultaneously, AP also conducted
to AV node
Bundle of His Interventricular septum
Dormant pacemaker It crosses over fibrous skeleton,
↓ brings AP delayed to ventricles;
Ventricles contract after atrias
Left and right bundle Bundle of His divides in
branches (2) Interventricular septum;
Dormant pacemaker AP hits apex, papillary muscles 1st
↓
Purkinje fibers Wall of ventricles 20-40 beat/min
Dormant pacemaker Terminal branches of the conduction • Autorhythmic
↓ system,
Ventricular syncytium in subendocardium CT;
AP travels upward from apex
 Purkinje fibers stuck between endocardium and myocardium
A Lumen of a ventricle (blood)
B Endothelium of endocardium (flat nucleus) + BM
C Sub-endothelial connective tissue: fibroblast + collagen
D Purkinje fibers in sub-endocardium
1 Lumen of a ventricle E Purkinje-Myocyte Junctions (PMJs)
2 Endocardium F Working Cardiac muscle tissue (cross cut: larger myofibrils at periphe
3 Myocardium
4 Epicardium A
F D blood
1
2
C
E

3 B
pink white

4
Cardiomyocytes (cardiac muscle cells)
Regular cardiac muscle tissue
Two Function:
• `Physiological Syncytium: Conducts action potential as
one big “cell” by gap junctions (cannot create)
• Contracts to pump blood
Cells are making fibers by intercalated discs (ICD)
Fibers are made out of cardiac muscle cells
Cells have desmosomes in ICD
Functional syncytium by gap junctions
ICD = interdigitations of 2 sarcolemma of 2 cardiomyocytes
Structures in ICD: desmosome, fascia adherens, gap junction
Cells have smaller diameter
Pink cytoplasm from myofibrils
Sarcoplasm is filled with myofibrils
Myofibrils make striations
Uninucleation or binucleation
Nucleus is smaller, in center
More nuclei are visible (smaller cells)
Lots of mitochondria
T-tubules, located at Z lines,
• Dyad: T tubule + one tubule of SR, No terminal cisterna
Location: myocardium of all 4 chambers
Autorhythmic cardiomyocytes)
Conduction system or “Intrinsic Nervous system” of heart (hierarchy)
It can be modified by Extrinsic Nervous system:
(Autonomic sympathetic nerves and parasympathetic Vagus X.)
Two Function:
• Creates and conducts action potential (conduction 4x faster)
Cells are making fibers, BUT fewer intercalated discs
Fibers are made out of Purkinje muscle cells
Cells have desmosomes, in ICD???
Functional syncytium by gap junctions
ICD (variable in appearance and number)
Cells have larger diameter
Pale or white cytoplasm from glycogen granules → resists hypoxia
Less myofibrils (at plasma membrane: periphery of cell, only)
Has few myofibrils and few striations, irregularly arranged under sarcolemma
Uninucleation or binucleation
Nucleus is bigger, in center
Less nuclei are visible (larger cells, so knife can miss them more)
Lots of mitochondria
No T-tubules
Location: sub-endocardium (between endocardium and myocardium)
 Purkinje-Myocyte Junctions (PMJs)
A Purkinje fibers in sub-endocardium
B Purkinje-Myocyte Junctions (PMJs)
C Working Cardiac muscle tissue (long. cut: myofibrils make striations)
A B C
 Diseases of the Endocardium

1 Endocarditis
2 Damage to endothelial cells leads to blood components adhere to the endocardium and
causes thrombus formation, because it is not smooth any more
3 Valvular heart disease
Rheumatic fever heart disease (after infection of throat by the bacterium Streptococcus)
Degeneration of valves
• Calcification
• Fibrosis
Jan Evangelista Purkyně:1787 – 1869
a Czech anatomist and physiologist 

• Purkinje fibers
• Purkinje neurons in cerebellum
• Plasma (blood)
• Protoplasm