The three major layers that make up the walls of the heart chambers are the endocardium, myocardium, and epicardium. The endocardium is the innermost layer and consists of endothelium, connective tissue, and smooth muscle fibers. The myocardium is the thickest layer and consists mainly of cardiac muscle fibers. The epicardium is the outermost layer and consists of a mesothelium, connective tissue, blood vessels, and nerves.

1. CVS HISTOLOGY

2. HEART

3. 3
The walls of all four heart chambers
consist of three major layers:
1. the internal endocardium;
2. the middle myocardium; and
3. the external epicardium.

4. Dr. R. Khasawneh 4
• The endocardium
consists of:
1. a very thin inner layer of
endothelium (En) and
supporting connective
tissue,
2. a middle myoelastic
layer of smooth muscle
fibers and connective
tissue, and
3. a deep layer of
connec-tive tissue called
the subendocardial
layer (SEn) that merges
with the myocardium.
(En) endothelium, (SEn) subendocardial layer, (P)
conducting (Purkinje) fibers, (M) contractile
cardiac muscle fibers. X200. H&E.

5. Dr. R. Khasawneh 5
• Branches of the heart’s
impulse-conducting
system (P), consisting of
modified cardiac muscle
fibers, are also located in
the subendocardial
layer (SEn).
• The thickest layer, the
myocardium (M),
consists mainly of
cardiac muscle with its
fibers arranged spirally
around each
heart chamber.
(En) endothelium, (SEn) subendocardial layer, (P)
conducting (Purkinje) fibers, (M) contractile
cardiac muscle fibers. X200. H&E.

6. 6
The epicardium (Ep) is a simple squamous mesothelium
(Mes) supported by a layer of loose connective tissue (CT)
containing blood vessels, nerves (N) and fat (F).
(M) myocardium, (Ep) epicardium, (CT) loose connective tissue, (N)
autonomic nerves, (F) fat, (Mes) mesothelium. X100. H&E.

7. 7
Dense fibrous connective tissue (C) of the cardiac skeleton
forms part of the interventricular and interatrial septa, surrounds
all valves (🡪) of the heart, and extends into the valve cusps and
the chordae tendineae (CT) to which they are attached.
(En) endocardium, (🡪) atrioventricular valve, (CT) chordae tendineae, (C) connective
tissue, (A) atrium, (V) ventricle, (M) myocardium. X20. Masson trichrome.

8. CARDIAC MUSCLE

9. 9
• Cardiac muscle cells form complex junctions between interdigitating
processes.
• Cells within a fiber often branch and bind to cells in adjacent fibers.
• Consequently, the heart consists of tightly knit bundles of cells,
interwoven in a fashion that provides for a characteristic wave of
contraction that resembles wringing out of the heart ventricles.

10. • Mature cardiac
muscle cells are
approximately 15 μm
in diameter and from
85 to 100 μm in
length.
• They exhibit a
cross-striated
banding pattern
comparable to that of
skeletal muscle.
• Unlike multinucleated skeletal muscle, however, each cardiac muscle cell
possesses only one (or two) centrally located, pale-staining nuclei.

11. 11
Surrounding the muscle cells is a delicate sheath
of endomysium with a rich capillary network.

12. 12
A unique and distinguishing characteristic of cardiac muscle is
the presence of dark-staining transverse lines that cross the
chains of cardiac cells at irregular intervals where the cells join.

13. 13
These intercalated discs represent the interface between
adjacent muscle cells and contain many junctional complexes.

14. • Transverse regions of these steplike discs have many
desmoso-mes and fascia adherentes (which resemble the zonula
adhe-rentes between epithelial cells);
• together these serve to bind cardiac muscle cells firmly together to
prevent their pulling apart under constant contractile activity.

15. • The longitudinally oriented portions of each disc have many gap
junctions providing ionic continuity between cells.
• These serve as “electrical synapses” and allow cells of cardiac
muscle to act like a multinucleated syncytium as in skeletal
muscle, with contraction signals passing in a wave from cell to cell.

16. 16
• Muscle cells from the heart
atrium show the presence of
membrane-bound granules
(G), mainly aggregated at the
nuclear poles.
• These granules are most
abundant in muscle cells of
the right atrium (~600 per
cell), but smaller quantities are
also found in the left atrium
and the ventricles.
• The atrial granules contain the
precursor of a polypeptide
hormone, atrial natriuretic
factor (ANF).
• ANF targets cells of the kidneys to bring about sodium and
water loss (natriuresis and diuresis).
• This hormone thus opposes the actions of aldosterone
and antidiuretic hormone, whose effects on kidneys
result in sodium and water conservation. X10,000.

17. TISSUES OF THE
VASCULAR WALL

18. Walls of all blood vessels
except capillaries contain
smooth muscle and
con-nective tissue in
addition to the endothelial
lining.

19. • The innermost tunica intima consists of:
• the endothelium and
• a thin subendothelial layer of loose connective tissue sometimes
containing smooth muscle fbers.
• In arteries and large veins, the intima includes a prominent limiting
layer, the internal elastic lamina, composed of elastin, with holes
allowing better diffusion of substances from blood deeper into the wall.

20. 20
• The tunica media, the
middle layer, consists
chiefly of concentric layers
of helically arranged
smooth muscle cells.
• Interposed among the
muscle fbers are variable
amounts of elastic fibers
and elastic lamellae,
reticular fbers, and
proteoglycans, all of which
are produced by the
smooth muscle cells.
• In arteries, the media may
have a thin external
elastic lamina, separating
it from the outermost tunic.

21. Dr. R. Khasawneh 21
• The outer adventitia,
or tunica externa,
consists principally of
type I collagen and
elastic fibers.
• The adventitia is
continuous with and
bound to the stromal
connective tissue of
the organ through
which the blood vessel
runs.

22. Elastic Arteries

23. Dr. R. Khasawneh 23
• Elastic arteries are:
✔ the aorta,
✔ the pulmonary artery, and
✔ their largest branches;
• these large vessels are also
called conducting arteries
because their major role is to
carry blood to smaller
arteries.

24. 24
• The most prominent feature
of elastic arteries is the
thick media (M) in which
elastic lamellae, each
about 10 μm thick, alternate
with layers of smooth
muscle fibers.
• The adult aorta has about
50 elastic lamellae.
Aorta. (🡪) simple squamous
endothelial cells, (I) intima, (IEL)
internal elastic lamina, (M) media, (A)
tunica adventitia, (V) vasa vasorum.
X122. Elastic stain.

25. Dr. R. Khasawneh 25
• The intima (I) is well
developed, with many smooth
muscle cells in the
subendo-thelial connective
tissue, and often shows folds in
cross section as a result of the
loss of blood pressure and
contraction of the vessel at
death.
• The internal elastic lamina
(IEL) is not easily discerned
because it is similar to the
elastic laminae of the next
layer.
• The adventitia (A) is much
thinner than the media.

26. Arterial Sensory Structures

27. 27
Carotid sinuses are
slight dilations of the
bilateral internal
carotid arteries
where they branch
from the (elastic)
common carotid
arteries; they act as
important
barore-ceptors
monitoring arterial
blood pressure.

28. 28
• At these sinuses the media
is thinner, allowing greater
distension when blood
pressure rises, and the
adventitia contains many
sensory nerve endings
from cranial nerve IX, the
glossopharyngeal nerve.
• The brain’s vasomotor
centers process these
afferent impulses and
adjust vasoconstriction,
maintaining normal blood
pressure.
• Functionally similar
baroreceptors are also
present in the aortic arch.

29. 29
Chemoreceptors
that monitor blood
levels of CO2
and
O2
, as well as its
hydrogen ion
con-centration (pH),
are found in the
carotid bodies and
aortic bodies,
located in the walls
of the carotid
sinuses and aortic
arch, respec-tively.
These structures are parts of the autonomic nervous
system called paraganglia with rich capillary networks.

30. Dr. R. Khasawneh 30
• The capillaries are closely
surrounded by numerous,
large, neural crest-derived
glomus (type I) cells (G)
filled with dense-core
vesi-cles containing
dopamine, acetylcholine, and
other neurotransmitters,
which are supported by
smaller satellite (type II)
cells (S).
• Appropriate ion channels in
the glomus cell membranes
respond to stimuli in the
arterial blood, primarily
hypoxia (low O2
),
hyper-capnia (excess CO2
),
or acidosis, by activating
release of neurotransmitters.
Glomus body. (C) capillaries, (G) glomus
cells, (S) satellite cells. X400. PT

31. Sensory fbers branching from the glossopharyngeal nerve form
synapses with the glomus cells and signal brain centers to initiate
cardiovascular and respiratory adjustments that correct the condition.

32. Muscular Arteries

33. The muscular arteries
distribute blood to the organs
and help regulate blood
pressure by contracting or
relaxing the
smooth muscle in the media.

34. 34
• The intima has a very
thin subendothelial layer
and a prominent
inter-nal elastic lamina
(IEL).
• The media (M) may
contain up to 40 layers
of large smooth muscle
cells (SM) interspersed
with a variable number
of elastic lamellae
(de-pending on the size
of the vessel).
Muscular artery. (E) endothelial
cells, (IEL) internal elastic lamina,
(SM) smooth muscle, (M) media,
(V) vasa vasorum. X100. H&E.

35. 35
An external elastic lamina, the last component of the
media, is present only in the larger muscular arteries.

36. 36
• The adventitia consists
of connective tissue.
• Lymphatic capillaries,
vasa vasorum (V), and
nerves are also found in
the adventitia, and these
structures may
pene-trate to the outer
part of the media.
Muscular artery. (E) endothelial
cells, (IEL) internal elastic lamina,
(SM) smooth muscle, (M) media,
(V) vasa vasorum. X100. H&E.

37. Arterioles

38. 38
Muscular arteries branch
repeatedly into smaller
and smaller arteries, until
reaching a size with three
or four medial layers
of smooth muscle.

39. 39
The smallest arteries
branch as arterioles
(A), which have only
one or two smooth
muscle layers; these
indicate the beginning
of an organ’s
micro-vasculature,
where exchanges
between blood and
tissue fluid occur.
(A) arterioles, (C) capillaries,
(V) venules, (L) lymphatic
vessels. 200X H&E.

40. 40
• Arterioles are generally
less than 0.1 mm in
dia-meter, with lumens
appro-ximately as wide as
the wall is thick.
• The subendothelial layer is
very thin, elastic laminae
are absent, and the media
(M) consists of the
circu-larly arranged smooth
muscle cells.
• In both small arteries and
arterioles, the adventitia
(Ad) is very thin and
in-conspicuous.
Arteriole. (I) intima, (E) endothelium,
(M) media, (Ad) adventitia. X350.
Masson trichrome.

41. 41
• Arterioles almost always
branch to form
anasto-mosing
networks or beds of
capillaries that surround
the parenchy-mal cells of
the organ.
• Smooth muscle fibers
act as sphincters
closing arterioles and
producing periodic blood
flow into capillaries.
• Acting as “resistance
vessels,” muscle tone
usually keeps arterioles
partially closed and
makes these vessels the
major determinants of
systemic blood pressure.

42. 42
• In certain tissues and organs arterioles deviate from this simple path
to accommodate various specialized functions.
• For example, thermoregulation by the skin involves arterioles that
can bypass capillary networks and connect directly to venules.

43. Dr. R. Khasawneh 43
• The media and
adven-titia are thicker in
these arteriovenous
shunts (or arteriovenous
anasto-moses) and richly
inner-vated by
sympathetic and
parasympathetic nerve
fibers.
• The autonomic fibers
control the degree of
vasoconstriction at the
shunts, regulating blood
flow through the capillary
beds.

44. 44
• Another important alternative
microvascular pathway is a venous
portal system, in which blood flows
through two successive capillary
beds separated by a portal vein.
• This arrangement allows for
hormones or nutrients picked up by
the blood in the first capillary
network to be delivered most
efficiently to cells around the second
capillary bed before the blood is
returned to the heart for general
distribution.
• The best examples are the hepatic
portal system of the liver and the
hypothalamic-hypophyseal portal
system in the anterior pituitary
gland, both of which have major
physiologic importance.

45. Capillary Beds

46. 46
• Capillaries permit and regulate metabolic exchange
between blood and surrounding tissues.
• These smallest blood vessels always function in groups
called capillary beds, whose size and overall shape
conforms to that of the structure supplied.
• The richness of the capillary network is related to the
metabolic activity of the tissues.
The blood vessels were
injected with a dark
plastic polymer before
the muscle was collected
and sectioned
longitu-dinally. A rich
network of capillaries in
endomy-sium
surrounding muscle
fibers is revealed by this
method. X200. Giemsa
with polarized light.

47. 47
• Capillary beds are supplied preferentially by one or more terminal
arteriole branches called metarterioles, which are continuous with
thoroughfare channels connected with the postcapillary venules.
• True capillaries branch from the metarterioles, which are encircled by
scattered smooth muscle cells, and converge into the thoroughfare
channels, which lack muscle.

48. • At the beginning of each true capillary, muscle fibers act as
precapil-lary sphincters that contract or relax to control the entry of
blood.
• These sphincters contract and relax cyclically, with 5 to 10 cycles per
minute, causing blood to pass through capillaries in a pulsatile manner.

49. 49
When the sphincters are closed, blood flows directly from the
metarterioles and thoroughfare channels into postcapillary venules.

50. 50
• Capillaries (C) are composed of a single layer of
endo-thelial cells rolled up as a tube.
• The average diameter of capillaries varies from 4 to 10 μm,
which allows transit of blood cells only one at a time, and
their individual length is usually not more than 50 μm.
C
A
V

51. Dr. R. Khasawneh 51
• Major structural variations in capillaries occur in
organs with various functions that permit very
different levels of metabolic exchange.
• Capillaries are generally grouped into three
histologic types, depending on the continuity of
the endothelial cells and the external lamina.

52. 52
1. Continuous capillaries have
many tight, well-developed
occluding junctions
between slightly overlapping
endothelial cells, which
provide for continuity along
the endothelium and
well-regulated metabolic
exchange across the cells.
• This is the most common
type of capillary and is
found in:
✔ muscle,
✔ connective tissue,
✔ lungs,
✔ exocrine glands, and
✔ nervous tissue.

53. Dr. R. Khasawneh 53
• Numerous transcytotic
vesicles (V) are evident.
• All material that crosses
continuous capillary
endo-thelium must pass
through the cells, usually
by diffu-sion or
transcytosis.
• Around the capillary are a
basal lamina (BL) and
thin cytoplasmic
exten-sions from
pericytes (P).
• Collagen fibers (C) and
other extracellular material
are present in the
perivas-cular space (PS).
TeM of a continuous capillary in transverse section. X10,000.

54. Dr. R. Khasawneh 54
2. Fenestrated capillaries
have a sieve-like
struc-ture that allows
more extensive molecular
exchange across the
endothelium.
• Fenestrated capillaries are
found in organs with rapid
interchange of substances
between tissues and the
blood, such as the:
✔ kidneys,
✔ intestine,
✔ choroid plexus, and
✔ endocrine glands.

55. 55
• The endothelial cells are penetrated by numerous small circular
openings or fenestrations, approximately 80 nm in diameter.
• Some fenestrations are covered by very thin diaphragms of
proteoglycans; others may represent membrane invaginations during
transcytosis that temporarily involve both sides of the very thin cells.
• The basal lamina is continuous and covers the fenestrations.
TeM of a transversely
sectioned fenestrated
capillary in the
peritu-bular region of the
kid-ney. (🡪) fenestrae
clo-sed by diaphragms,
(BL) continuous basal
lamina surrounding the
endo-thelial cell, (G)
golgi ap-paratus, (N)
nucleus, (C) centrioles.
X10,000.

56. Dr. R. Khasawneh 56
3. Discontinuous
capillaries, commonly
called sinusoids, permit
maximal exchange of
macromolecules as
well as allow easier
movement of cells
between tissues and
blood.
• Sinusoidal capillaries
are found in the:
✔ liver,
✔ spleen,
✔ some endocrine
organs, and
✔ bone marrow.

57. • Individual endothelial cells here have large perforations without
diaphragms; collectively they form a discontinuous layer, with
wide, irregular spaces between the cells.
• Sinusoids (S) also differ from other capillaries by having
❖ highly discontinuous basal laminae and
❖ much larger diameters, often 30 to 40 μm, which slows blood flow.
Bone marrow. (S)
sinusoid, (A)
adipocytes, (H)
hematopoietic
cells. X200. H&E.

58. 58
At various locations along continuous capillaries and postcapillary
venules are mesenchymal cells called pericytes (P).
Spread mesentery preparation. (P) pericytes. X400. H&E

59. • Pericytes (P) have long
cyto-plasmic processes partly
sur-rounding the endothelial
layer.
• They produce their own basal
lamina (BL), which may fuse
with that of the endothelial
cells.
• Well-developed networks of
myosin, actin, and
tropomyo-sin in pericytes
indicate these cells’ primary
contractile func-tion to
facilitate flow of blood cells.
• After tissue injuries,
peri-cytes proliferate and
diffe-rentiate to form smooth
mus-cle and other cells in
new vessels as the
microvascu-lature is
re-established.
TeM of a capillary cut transversely. (E) endothelial
cell, (L) capillary lumen, (BL) basal lamina, (J)
junctional complexes, (P) pericyte, (BL) basal
lamina of pericicyte. X13,000.

60. Venules

61. (A) arterioles, (V) postcapillary venules, (P) pericytes. X400. Toluidine blue (TB).
• The transition from capillaries to venules occurs gradually.
• The immediate postcapillary venules (V) are similar structurally to
capillaries with pericytes, but range in diameter from 15 to 20 μm.

62. 62
A characteristic feature of all venules is the large diameter of
the lumen compared to the overall thinness of the wall.
(V) collecting venules, (A) arterioles. X200. Toluidine blue.

63. 63
• Postcapillary venules
converge into larger
collecting venules
that have more
contractile cells.
• With even greater size,
the venules become
surrounded by a
recognizable tunica
media with two or three
smooth muscle layers
and are called
muscular venules.
Muscular venule cut lengthwise.
(M) smooth muscle, (I) intima, (E)
endothelial cells, (Ad) adventitia,
(A) part of an arteriole. X200.
Masson trichrome.

64. 64
Postcapillary venules (V) are the primary site at which
white blood cells adhere to endothelium and leave the
circulation at sites of infection or tissue damage.
Postcapillary venule (V) from an infected small intestine shows several
leukocytes adhering to and migrating across the intima. X200. H&E.

65. Veins

66. 66
• Most veins are small or medium veins, with diameters of 10 mm or less.
• Such veins are usually located close and parallel to corresponding
muscular arteries.
(V) small vein, (A) small muscular artery, (M) media, (Ad). Adventitia. X200. H&E.

67. 67
• In medium veins, the intima usually has a thin subendothelial layer,
and the media consists of small bundles of smooth muscle cells
intermixed with reticular fibers and a delicate network of elastic fibers.
• The collagenous adventitial layer is well developed.
(MV) medium vein, (MA) muscular artery. X100. H&E.

68. 68
• The big venous trunks, paired
with elastic arteries close to the
heart, are the large veins.
• Large veins have a
well-deve-loped intima (I), but
the media (M) is relatively thin,
with alter-nating layers of
smooth muscle and connective
tissue.
• The adventitial layer (A) is
thicker than the media in large
veins and frequently contains
longitudinal bundles of smooth
muscle.
Vena cava. (🡪) Simple squamous
endothelial cells, (I) intima, (IEL) internal
elastic lamina, (M) media, (A) adventitia,
(EF) elastic fibers, X122. Elastic stain.

69. 69
• Medium and large veins have valves consisting of paired
folds of the intima projecting across the lumen.
• They are rich in elastic fibers and are lined on both sides by
endothelium.
• The valves, which are especially numerous in veins of the legs,
help keep the flow of venous blood directed toward the heart.
Large vein. (M)
media layer, (A)
adventitia, (I)
intima, (V) valve.
X100. PT.

70. GOOD LUCK