U

UČČE
EBBN
N ÍÍ T
TEEX
XTTY
Y U
UNN II V
VEER
RZZ II T
TYY K
KAAR
R LL O
OVVY
Y V
V P
PRRA
AZZE
E
EXTY UNIVERZITY KARLOVY V PRAZE

COVER

OUTLINES
ZÁKLADY
OF HISTOLOGY
HISTOLOGIE
Jaroslav Slípka
Jaroslav Slípka
Zbyněk Tonar

KAROLINUM
Outlines of Histology

Jaroslav Slípka
Zbyněk Tonar

Reviewed by:
Sarah Leupen, Department of Biological Sciences, University of Maryland
Baltimore County, USA
Ivan Varga, Institute of Histology and Embryology, Faculty of Medicine,
Comenius University, Bratislava, Slovakia

Published by Charles University

Karolinum Press
as a teaching text for the Faculty of Medicine in Pilsen
Typesed by DTP Karolinum Press
Second, revised edition

© Charles University, 2017

Jaroslav Slípka – heirs, Zbyněk Tonar, 2017

ISBN 978-80-246-3743-3
ISBN 978-80-246-3758-7 (online : pdf)

Charles University
Karolinum Press 2017

www.karolinum.cz
ebooks@karolinum.cz
CONTENTS

Cover . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Contents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
PREFACE. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

PART I: THE CELL. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

Cell membranes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Nucleus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Chromatin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Cell cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Mitosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Ribosomes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
Endoplasmic reticulum (ER). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
Rough (granular) endoplasmic reticulum – RER (GER). . . . . . . . . . . . . . . . . 24
Smooth (agranular) endoplasmic reticulum – SER (AER). . . . . . . . . . . . . . . . 26
Golgi complex (Golgi apparatus). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
Mitochondria. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Lysosomes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
Peroxisomes (microbodies). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Nonmembranous organelles and cytoskeleton. . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Microtubules. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Centrosome (diplosome). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Microfilaments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
Intermediate filaments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
Cell inclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

PART II: THE TISSUES. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

A. Epithelial tissue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
Apical surface of epithelia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
Basement membrane. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
Cell adhesion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
Junctional complex. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
Covering epithelia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
 Simple epithelia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
Stratified epithelia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
Glandular epithelia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
Exocrine glands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
Classification of exocrine glands according to shape . . . . . . . . . . . . . 41
Glands according to the mechanism of secretion . . . . . . . . . . . . . . . . 42
Glands according to their secretory products. . . . . . . . . . . . . . . . . . . . 42
Myoepithelial cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
B. Connective tissue. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
Connective tissue proper. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
Cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
Extracellular matrix. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
Fibers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
Ground substance. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
The types of connective tissue proper . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
Cartilage. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
Hyaline cartilage. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
Elastic cartilage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
Fibrocartilage. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
Bone. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
Spongy (cancellous, trabecular) bone . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
Compact bone. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
Ossification. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
Intramembranous ossification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
Endochondral ossification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
Tooth. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
Development of the teeth. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
Histology of the tooth components . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
Enamel. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
Dentin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
Cement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
Periodontal membrane. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
The pulp. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
Alveolar bone and gingiva. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
Blood . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
Plasma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
Erythrocytes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
Leukocytes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
Granulocytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
Agranulocytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
Thrombocytes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
Hematopoiesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
C. Muscle tissue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
Smooth muscle. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
Striated (sarcomeric) muscle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
Skeletal muscle. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
Mechanism of contraction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
Myosatellite cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
Cardiac muscle. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
Cardiac conducting system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
Specialized myocardiocytes – myoendocrine cells. . . . . . . . . . . . . . . 95
D. Nerve tissue. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
Neurons. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
Classification of neurons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
Cytology of the neuron. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
Unmyelinated fibers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
Myelinated fibers of CNS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
Peripheral nerve. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
Synapses and a reflex arc. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
Sensory receptors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
Free nerve endings. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
Meissner’s corpuscles. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106
Pacinian corpuscles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106
Muscle spindles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106
Motor nerve endings. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
Conduction of nerve impulses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
Neuroglia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
Astrocytes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
Oligodendrocytes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
Microglia cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
Ependymal cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
Satellite cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
Meninges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
Pia mater. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
Arachnoid. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
Dura mater. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
Blood-brain barrier. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
Cerebrospinal fluid. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116

Figure captions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118

Literature recommended for further study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
PREFACE

Histology is a science of the tissues which are formed by conglomer-

ation of cells and extracellular matrix. We are always interested in under-
standing the origin, microscopic structure and function of these tissues.
Contemporary general histology deals – in addition to the description
of the fundamental unit of the tissue, the cell – with four kinds of basic
tissues, presented in this textbook. These tissues participate in construction
of various organs and organ systems.
This textbook outlines the courses in general histology, given to the
international students of general and dental medicine in the first year of
their pregraduate studies at the Charles University, Faculty of Medicine
in Pilsen. The first edition was prepared in 1994 and revised in 2004 by
Prof. Dr. Jaroslav Slípka, DSc (1926–2013), who was an enthusiastic and
inspiring researcher and teacher at the Department of Histology and Em-
bryology. The second edition was updated in 2017 to reflect some of the
advances in teaching of histology. Nevertheless, the illustrations and the
concise concept of the book designed originally by prof. Slípka were kept.
We recommend using this textbook for revising and summarizing the es-
sential knowledge. For full color textbooks and atlases that are necessary
for understanding the histological slides, see the literature recommended
at the end.
We wish all our students might enjoy the insight into the universe of
cells and tissues the human body is made of. Welcome to the world of
Histology!

Zbyněk Tonar
Pilsen, 2017

–7–
PART I: THE CELL

The cell is a basic integrated entity of all living organisms. It is a funda-

mental morphologic and physiologic unit, capable of multiplication, metab-
olism, growth, excitability and other specialized functions. The microscopic
analysis of the fine structure and function of cells is referred to as cytology.
There are two different structural types of cells:
Prokaryotic cells with no nuclear membrane and no membranous orga-
nelles like in bacteria.
Eukaryotic cells with a nuclear membrane and various membranous
organelles. These cells can form assemblies, classified into four basic tis-
sues in multicellular animals (Metazoa). The science of the morphologic
and functional features of cells and tissues constitutes histology, the topic
of this textbook.
Shapes and dimensions of cells: Although the primary form of cells is
rounded or spherical, during development of tissues cells become, depend-
ing on their function, squamous, cuboidal, columnar, pyramidal, spindle

Fig. 1 Shapes of cells

–8–
shaped, star shaped, goblet shaped etc. The shape of cells is organized by
an internal scaffolding of proteins known as the cytoskeleton. Those cells
which have remained free, e.g. blood cells, retain their spherical form. Most
of the cells of the human body range from 4–30 micrometers in diameter;
the largest are the oocytes (150 µm in human). The red blood cell, which
ranges around 7.5 µm in diameter, can be used as a rough measure of the
size of the tissue cells seen in the same field.
Composition of cells: The cell is formed by protoplasm which is
composed of cytoplasm (or cytosol), the fluid matrix of the cell, and nu-
cleoplasm, the matrix of the nucleus. Cytoplasm is composed of a colloid
solution, contained by a cell (or plasma) membrane – plasmalemma. The
cytoplasm contains many smaller elements – subcellular structures – called
organelles which provide the framework for cellular activities. It contains
also many of the essential enzymes and metabolites. In the nucleoplasm is
the genetic material in the form of chromosomes. Chemical composition of
cells: in addition to water and inorganic substances, cells contain four main
classes of organic constituents: proteins, carbohydrates, fats (lipids) and

Fig. 2 The cell

–9–
nucleic acids. The pH of the cytoplasm ranges between 7.0–7.4. However,
in most histological staining methods, the cytoplasm of most cells appears
as slightly acidophilic (e.g., stained pink to reddish by an acidic dye named
eosin using the routine hematoxylin-eosin staining).

Cell membranes

The term comprises not only the outer membrane surrounding each cell,
i.e. plasmalemma, but also the membranes surrounding cellular organelles.
The basic structure consists of a lipid bilayer containing specialized pro-
teins in association with surface carbohydrates.
The membrane lipids are of three types: phospholipids, cholesterol and
glycolipids. The phospholipids are organized into a double layer of mole-
cules, in which each molecule has an outer hydrophilic head and an inner
hydrophobic chain. Cholesterol is inserted into the phospholipid bilayer and
is present in about the same amounts as are phospholipids, and is responsi-
ble for the mechanical stability of the otherwise fluid membrane. Glycolip-
ids with their associated sugars are exposed to the extracellular surface and
are involved together with glycoproteins in intercellular communication as
mediators of cellular interactions like adhesion and recognition.
Membrane protein molecules can be classified according to their spa-
tial relations to the membrane: Integral (intrinsic) membrane proteins of-

Fig. 3 Cell membrane

– 10 –
ten span the whole lipid bilayer from one surface to another, and form
a transmembrane channel for passing the ions through the membrane. Some
integral membrane proteins are confined to the inner or outer part of the
membrane only. The peripheral (extrinsic) membrane proteins are not fully
embedded within the lipid bilayer and are more loosely attached to a mem-
brane surface.
Some membrane proteins are receptors, which allow cells to respond
to external signals when binding a variety of signaling molecules (or li-
gands). Binding of signaling molecules (released by a signaling cell) to
their receptors activates in the target cell an intracellular second messenger
system, initiating a cascade of reactions that result in the required response.
For example, a hormone (the first messenger) activates through a receptor
a transmembrane protein – adenylate cyclase, which in cytoplasmic region
catalysates the transformation of ATP to cyclic adenosine monophosphate
(cAMP), i.e. the second messenger.
Numerous membrane proteins bear polysaccharide chains and represent
the glycoprotein molecules. The membrane carbohydrates cover the extra-
cellular surface of the cell membrane like a sugar coating – the glycocalyx.
The polysaccharide chains confer a certain surface specificity on every type

Fig. 4 Cellular processing of external signals

– 11 –
Fig. 5 Membrane transport

of cell. The glycocalyx is directly involved in the recognition and adhesion

of different cell types, particularly during morphogenesis. The carbohy-
drate chains can be demonstrated by staining with lectins (proteins extract-
ed mostly from some plants).
The role of the cell membrane lies not only in preserving the integrity
of the cell, but also in cell-cell recognition and selective transport of mole-
cules. Whereas the cell membrane is impermeable to most large molecules,
it is permeable to some smaller molecules and ions, and so important for
bringing needed material into the cell and releasing waste products. The
membrane is equipped with active transport mechanisms to transfer vari-
ous substances (e.g., glucose, amino acids) in the required direction. Small
molecules are bound to an integral carrier protein which undergoes series of
conformational (shape) changes to release the molecule on the cytoplasmic
side. Some ions can be transported according to the ion gradient through
the plasmalemma by ion selective channel proteins via a mechanism called
facilitated diffusion. Another example is a sodium-potassium pump which
utilizes energy from mitochondria to release the sodium ions from the cell
and to pump potassium into the cell (see, e.g., nerve tissue).
The cell can also ingest macromolecules from the extracellular space
by invagination of the cell surface, termed endocytosis. The invaginated
cell membrane encloses the incorporated material for further processing
in an endocytotic vesicle (endosome). In the case of very small molecules,
we specify the endocytotic process as pinocytosis (i.e. cell drinking) with
the formation of pinocytotic vesicles. For ingestion of large particles (e.g.
bacteria) the term phagocytosis (cell eating) is used. In such cases the cell

– 12 –
extends cytoplasmic processes which engulf the material and ingest it in
endosomes, called phagosomes.
The reverse process is called exocytosis, in which the products produced
in cells can be released. The membrane bound vesicles fuse with cell sur-
face and discharge their content into the extracellular space.
The invaginated cell membrane forms a so called coated pit, which bears
surface receptors that bind specific extracellular ligands. The pit is covered
on the cytosolic side by a coat protein – clathrin – in form of a lattice. The
invaginated membrane then fuses to form an endocytic vesicle – endosome

Fig. 6 Exocytosis and endocytosis

Fig. 7 Transcytosis

– 13 –
(pha­gosome). During the process of internalization the clathrin is shed and
returns to the surface.
Similar membrane invaginations, coated with another protein – caveo-
lin – have been termed the caveoli. They are responsible for the transport of
the substances in vesicles from one side of a flat cell (e.g., endothelium lin-
ing the blood and lymph vessels) to the opposite one. This process is called
transcytosis. Their receptors can also play a role in intracellular signaling
by triggering the intercellular messenger system (e.g., in smooth muscle).

Nucleus

The nucleus is the largest membrane-limited, spherical or ovoid orga-

nelle, situated usually in the center of the cell (missing only in mature mam-
malian RBCs). Its diameter usually varies between 5–10 µm. It is composed
of nucleoplasm, which contains chromatin, and the nucleolus. The nucleus
is separated from the cytoplasm by the nuclear membrane (nucleolemma).
The nuclear membrane is built by two concentric membranes, sep-
arated by a narrow space – the perinuclear space, which can be contin-
uous with the rough endoplasmic reticulum. On the inner membrane are
anchored some filamentous proteins – lamins, which form a sort of scaf-
folding of the nucleoplasm. The outer nuclear membrane can be associated
with ribosomes. Both membranes fuse in numerous circular nuclear pores,
which are not open, but bridged by a thin protein diaphragm, permeable to
some molecules, e.g., to mRNA.

Fig. 8 Nucleus

– 14 –
 The nucleolus is a dense nonmembranous structure within the nucleus,
seen during interphase only. It measures 1–3 µm. Active cells (embryon-
ic, tumorous etc.) have usually larger or even multiple nucleoli. It stains
basophilic, being rich in rRNA and proteins, and it disappears during cell
division, but reappears in the telophase stage of mitosis.
The nucleolus is rich in rRNA and protein, accumulated into ribosomal
subunits, which are then transferred to cytosol through the nuclear pores.
It consists of three distinct regions. The pale area – fibrillar center – sur-
rounds the so called nucleolar organizer DNA regions. There the tips of 5
chromosomes are located and their genes (nucleolar organizers) code for
rRNA. The dark thread-like structure, the dense fibrillar component, con-
sists of primary transcripts of rRNA molecules beginning to form ribo-
somes. The granular regions – granular components – consist of maturing
ribosomal subunits.

Chromatin

There are two forms of chromatin: Heterochromatin is seen as con-

densed basophilic clusters of coarse granules, often adjacent to the nuclear
membrane. It represents an inactive form of chromatin. Euchromatin rep-
resents actively transcribed DNA and appears as lightly stained areas of
nucleoplasm. Its structure is seen in the electron microscope only.
A molecule of deoxyribonucleic acid (DNA) is made up of two polynu-
cleotide strands wound together in the form of a double helix. Each strand
consists of alternating phosphate and deoxyribose sugar groups, and it has
a nitrogenous base extending as a side chain from each sugar group into the
double helix. There are two types of bases: purines (adenine and guanine),
and the pyrimidines (cytosine and thymine).
There is an obligatory pairing of the bases on one strand by hydrogen
bonds with the bases on the other. Such complementary base pairing exists
between adenine (A) and thymine (T), and between guanine (G) and cy-
tosine (C). The building blocks of nucleic acids are the nucleotides, com-
posed of bases linked to sugar and phosphate groups.
DNA is the repository of genetic information. The information transfer
from the nucleotide sequence of DNA to the amino acid sequence of a pro-
tein involves three forms of RNA – ribosomal (rRNA), transfer (tRNA)
and messenger (mRNA). The molecule of ribonucleic acid (RNA) is single
stranded and is not self-replicating, so that all forms of RNA are tran-

– 15 –
Fig. 9 Molecule of DNA

scribed from DNA. DNA serves as a template for a complementary strand

of RNA during a process of transcription. RNA differs from DNA. The
sugar ribose is present instead of deoxyribose and the base uracil (U) re-
places thymine (T).
Chromatin is formed mainly by coiled strands of DNA, wound around
proteins – histones. The basic unit of chromatin is the nucleosome. Nucle-
osomes are regularly repeated globular structures, like beads on a string.
The nucleosomes form a chromatin fiber of 30 nm in diameter. Coiled chro-
matin fibers surround the chromosome protein core during cell replication
and are extensively condensed to form distinct chromosomes, structures
that are visible with the light microscope.
The mitotic chromosome possesses two arms, extending from its cen-
tromere. The adenine-thymine-rich regions of chromosomes produce a pat-
tern of G bands (stained with Giemsa stain), unique for each chromosome
and characteristic for each species. The units of heredity are located at spe-
cific regions on the DNA molecule and are called genes. Each gene repre-

– 16 –
Fig. 10 Chromatin fiber

sents a specific segment of the DNA molecule that codes for the synthesis
of a particular protein.
The number of chromosomes is specific for each species of living
organism. The number and type of chromosomes in an individual is known
as his or her karyotype. The human genome is made up of 46 chromosomes.
This diploid number represents 23 homologous pairs of chromosomes. Of
these 22 pairs are autosomes, and one pair represents sex chromosomes
(heterochromosomes, allosomes). The germ cell has only 23 chromosomes

Fig. 11 Condensed chromosome visible and stained during mitosis

– 17 –
(haploid number), from which are 22 autosomes, and one sex chromosome,
which differs in female and in male germ cells. In females, each ovum
always contains an X chromosome, while in males the spermatozoa are of
two kinds – one carrying sex chromosome X and the other Y. The resulting
sex of a newborn depends on the kind of sperm which fertilizes the ovum.
A male somatic cell then possesses 44 autosomes and XY combination of
sex chromosomes, whereas a female has also 44 autosomes, but XX sex
chromosomes.

Fig. 12 Human male karyotype

Only one of the two XX sex chromosomes of the female somatic cell
is activated during interphase. The other one is inactive and appears con-
densed as a clump of heterochromatin attached to the nuclear membrane
in form of a Barr body. It can be observed in 20–40% of epithelial cells in
smears taken from the oral mucosa or in form of a small drumstick attached
to the nucleus of the neutrophilic granulocytes.

– 18 –
Fig. 13 Barr body in a neutrophilic granulocyte of a female

Cell cycle

The somatic cells exist in the states of division (mitosis) and nondivision
(interphase). Interphase represents a longer period between mitotic division
that begins immediately following telophase of the mitosis. It cannot be
considered as a resting stage, because during this period of time the cell
increases its size and replicates its genetic material.

Fig. 14 DNA replication and doubling of chromatids

– 19 –
Fig. 15 Cell cycle and average duration of its phases

The two DNA strands unwind and separate and each strand serves as
a template for the synthesis of new strand alongside it. Complementary
base pairing occurs determined according the base sequence of preexisting
strand. Two identical double-stranded DNA molecules are formed – one
half persisting from the original one and the second half being synthesized
anew.
Interphase can be subdivided into three phases: During the G1 (gap)
phase when the synthesis of material essential for DNA duplication begins,
the nucleolus reappears and the centrioles begin their duplication. The next
stage is represented by S phase (synthetic), when the genome is duplicated
and the cell contains twice its usual complement of DNA in preparation for
the mitosis. During the last stage of the interphase, the G2 phase, the RNA
and proteins essential to cell division are synthesized, and energy is stored
so that the cell is prepared for mitosis.

Mitosis

Mitosis represents a short period in which the cell divides its nucleus and
cytoplasm into two identical daughter cells. During mitosis the 46 chromo-
somes become highly condensed. In the cytoplasm spindle fibers appear
and the centrioles split and migrate to opposite ends of the cell, where they
act as organizing centers for the spindles.

– 20 –
 Mitosis is a continuous process, but can be conventionally divided
into four main phases. During prophase the chromosomes become visi-
ble and split longitudinally except at the centromere. Each half, joined by
the centromere, is known as a chromatid. Next to the centromere on each
chromatid a new microtubule organizing center, the kinetochore, develops.
The nucleolus disappears and the nuclear membrane breaks down. In the
cytoplasm the spindle fibers stretch between the centrioles. The process of
nuclear material division is called karyokinesis.
During metaphase the chromosomes move accompanied in their migra-
tion by mitotic spindle microtubules. The chromosomes become maximally
condensed and arrange themselves at the equator of the cell, in form of a star.
In the next stage of anaphase the centromeres split and the sister chro-
matids become 92 separate chromosomes. The daughter chromosomes be-
gin to separate from each other and move to opposite sides of the cell. Each
daughter cell receives an identical set of 46 chromosomes, arranged on the
cell poles in a double star pattern.
In the last mitotic stage – telophase – the division of the cytoplasm
occurs (cytokinesis). The nuclear membrane forms and the spindle fibers
disintegrate and the nucleoli reappear. The 46 chromosomes of the daughter
cells condense and the nucleus reforms. The chromosomes begin a cycle of
decondensation and become dispersed throughout the nucleus in form of
chromatin.

Fig. 16 Chromosomes during mitotic cell division

The central dogma of molecular biology:

DNA → transcription → RNA → translation → protein

The central dogma of molecular biology describes the process of ex-

pression of the genetic information stored in the DNA molecule and the

– 21 –
Fig. 17 From genetic information to the protein

transfer of sequence information between information-carrying biopoly-

mers. This process requires two steps. At first the genetic information has to
be copied into messenger RNA (mRNA) in a process known as transcrip-
tion. The information for the insertion of a specific amino acid in a protein
is encoded in mRNA in a triplet of bases, a three-letter code, or codon.
The mRNA passes into the cytoplasm, where the message has to be put
into the language of the newly formed molecule of protein. This second
step of the process, known as translation, requires an interaction of many
components along with the mRNA, including the ribosomes, tRNA, amino
acids, enzymes and energy sources. Ribosomes serve as workbenches upon
which protein synthesis occurs. The transfer RNA (tRNA) contains a bind-
ing site for a specific type of amino acid and a three base segment known
as anticodon. Within the ribosome the anticodon recognizes and binds to
the complementary base sequence (codon) in mRNA, producing a poly-
peptide chain, which is released from the ribosome, e.g., to endoplasmic
reticulum. The ultimate expression of this information in the phenotype are
the proteins.

– 22 –
 Note: The central dogma was stated in 1958 by Francis Crick, a co-dis-
coverer of the structure of DNA molecule. Although it remains a fundamen-
tal concept, there are now several known ways of transfer of biological
sequential information, that are not covered by this dogma, such as reverse
transcription, RNA replication, posttranslational modification, methylation
of DNA, and others.

Ribosomes

Ribosomes are smallest, basophilic, electron-dense cellular organelles

(20–30 nm). They occur in great numbers free in the cytoplasm, or attached
to the membranes, mostly of endoplasmic reticulum. The free ribosomes
appear often in clusters, called polyribosomes or polysomes and synthesize
proteins which are required for uses within the cell. The ribosomes attached
to membranes are involved in synthesis of proteins that will be secreted out
of the cell.
The ribosomes are composed of ribosomal RNA (rRNA) and proteins,
the rRNA being synthesized in nucleolus and protein in the cytoplasm.
They appear in two different sized subunits, that associate to form a single
ribosome (or monosome) during protein synthesis, and which leave the nu-
cleus via nuclear pores.

Fig. 18 Ribosome

– 23 –
 The large subunit contains two rRNA molecules and more than 50 pro-
teins; the small one consists of a molecule of rRNA (different than those in
the large part) and more than 25–30 proteins. The small subunit contains
a site that binds mRNA, and a decoding region that binds a tRNA molecule.
The large subunit contains sites where amino acids are joined together and
the exit point for the newly synthesized protein. The ribosomes are held
together by a strand of messenger RNA, carrying the information of the
amino acid sequence of proteins which should be synthesized during trans-
lation. This is the final stage of the directional flow of genetic information
from DNA through RNA to protein, as stated by the central dogma of mo-
lecular biology.

Endoplasmic reticulum (ER)

The endoplasmic reticulum is a system of membranous, mostly flattened

channels, arranged into sheets within the cytoplasm. Their quantity depends
on cellular metabolic requirements (it is absent in mature erythrocytes, but
still present in erythroblasts). Cells which synthesize and secrete proteins
contain vast amounts of ER. There are two specialized types of ER: the
rough – RER (granular) and smooth – SER (agranular).

Rough (granular) endoplasmic reticulum – RER (GER)

RER is well developed in protein secreting cells (e.g., exocrine pancre-

atic cells, fibroblasts, plasma cells etc.). Its rough-surfaced limiting mem-
brane is studded with ribosomes, which become bound to the membrane of
ER as soon as the protein synthesis begins. When the synthesis of a poly-
peptide chain begins, a part of the amino acid sequence – signal recognition
particle – specifically recognizes the ER membrane and binds to a receptor
in it (a so called docking protein). This signal portion also instructs the
growing protein molecule to pass through this membrane into the lumen of
RER. Finally, the attachment of sugar groups to most molecules that will
become glycoproteins begins in the lumen of RER. The proteins are then
delivered by transfer vesicles to the Golgi apparatus. After completion of
peptide synthesis, the ribosome detaches from the docking protein and re-
turns free into the cytoplasm. Due to the numbers of ribosomes the RER has
a strong affinity for basic dyes and therefore cells specialized for synthesis

– 24 –
of proteins have usually amounts of basophilic RER in their cytoplasm. In
neurons, the RER is called Nissl bodies.

Fig. 19 Rough endoplasmic reticulum (RER)

– 25 –
Smooth (agranular) endoplasmic reticulum – SER (AER)

The SER also forms a membranous (more tubular) network within the
cell, but lacks associated ribosomes and is therefore called agranular. It
is a vital cell membrane system, because it is the site of cell lipid synthe-
sis, particularly membrane phospholipids. The lipid synthetic enzymes are
located on the outer side of SER. The newly formed phospholipids from
the lipid precursors are taken through the SER outer membrane bilayer by
specific transport proteins (so called flippases). In muscle cells and fib-
ers SER appears in the form of sarcoplasmic reticulum and it stores and
releases intracellular calcium ions which regulate the muscle contraction.
SER is also abundant in liver cells, where it is involved chemical modifi-
cations (biotransformation) of many molecules and also in metabolism of
cholesterol and other lipids. In some endocrine organs (e.g., adrenal cortex,
Leydig cells of testis, or cells of the ovarian corpus luteum) it is engaged in
biosynthesis of steroid hormones.

Golgi complex (Golgi apparatus)

This system of flattened and parallel-arranged cisterns, vesicles and vac-

uoles is situated usually around the nucleus (sometimes shifted towards the
apical pole of the cell). It represents an intermediary between the endo-
plasmic reticulum and the rest of cell. It plays a central role in the process
of secretion, being responsible for the chemical modification of secretory
products. Equally important is the role in distribution and packing the prod-
ucts of ER into secretory vesicles and also packing hydrolytic enzymes into
lysosomes.
There are at least two structural and functional parts of Golgi: The nu-
clear-facing convex cis face receives transport vesicles from ER. On the
opposite side of Golgi is the concave trans face, where the Golgi vacuoles
accumulate. During transit of material through this Golgi complex glyco-
sylation (adding saccharide side chains), sulphation, phosphorylation and
partial proteolysis occur. The final contents of the vesicles can then be dis-
tributed to secretory granules, lysosomes, or the plasma membrane. The
secretory vesicles which coalesce at the cell membrane can release their
content extracellulary in a process of exocytosis.

– 26 –
Mitochondria

These are the “power plants of the cell”, because of their capability to
transform the chemical energy stored in molecules of glucose, fatty acids
and amino acids into the production of the energy-rich compound adenosine
triphosphate (ATP) from its precursor adenosine diphosphate (ADP) by the
process of oxidative phosphorylation. The energy stored in ATP can be liber-
ated again by hydrolysis to ADP and can be applied to various energy-con-
suming processes in the cell. The ADP is then rephosphorylated to ATP.
Mitochondria appear in variable numbers in each cell, but in great num-
bers in cells that require great amounts of energy (e.g., several thousands
of mitochondria in in each liver cell). The mitochondria may be randomly
distributed, or they may be concentrated at the sites of high energy utili-
zation. They are usually of nearly spherical or ellipsoidal shape and about
0.5–2 µm long. They are believed to have evolved in eukaryotic cells as
symbiotic prokaryotic organisms similar to bacteria. Each mitochondrion
has its own DNA (mtDNA) and system for protein synthesis independent of
the cell nucleus. Their genetic material is of maternal origin, i.e., derived
from mitochondria present in ovum, with no paternal contribution. It is
important to know that abnormal mitochondrial DNA can lead to defective
cell functions and finally to developmental abnormalities of some organ
systems, like muscle and nervous system.

Fig. 20 Mitochondrion

– 27 –
 Mitochondria are enclosed by two membranes, separated by a narrow
space. The outer membrane is porous and smooth in outline; the inner one
is folded into series of extensions called cristae, which project into the inte-
rior and increase the whole surface area. The internal mitochondrial cavity
is filled by mitochondrial matrix, which contains mtDNA, mtRNA (of all
three types), ribosomes and proteins, as well as granules of calcium ions
accumulations. The matrix is also the site of enzymes of the Krebs (citric
acid) cycle and those concerned with protein and lipid synthesis. On the
cristae many tiny globular structures are located – the inner membrane sub-
units. They consist of a globular head and a slender stalk and their enzymes
are mostly involved in oxidative phosphorylation.

Lysosomes

Lysosomes are membrane-limited organelles 0.25–0.5 µm in diameter,

containing a number of hydrolytic enzymes, operating in an acid pH (acid
hydrolases). They represent an intracellular digestive system, and their en-
zymes can break down all classes of macromolecules. These lytic enzymes
are prevented by the enveloping lysosomal membrane from digesting the
other cell organelles. The lysosomal enzymes are synthesized in the RER
and packaged in small primary lysosomes in Golgi complex. The digestive
process occurs in larger secondary lysosomes. The resulting nutrients then
diffuse into cytoplasm, while the indigestible remnants remain in so called
residual bodies (e.g., accumulation of pigment lipofuscin during ageing).
The lysosomes play an important role in the process of phagocytosis, i.e.,
digestion of material taken up from the extracellular environment (known
as heterophagy). The particle becomes at first engulfed by cell membrane
in form of a phagocytic vesicle, which then enters the cytoplasm as so-
called phagosome. Its membrane then fuses with the membrane of the
primary lysosome which empties its enzymes in the phagocytic vesicle,
starting the digestion in the newly created secondary vesicle. The residual
bodies can be then extruded by exocytosis. In a similar process of auto-
phagy the digested particles are of intracellular origin (organelles or parts
of cytoplasm). This process occurs during reconstruction of the cytoplas-
mic content and is known in cells undergoing atrophy, or some hyperactive
secretory cells.

– 28 –
Peroxisomes (microbodies)

These are small (0.5–1 µm) membrane-bound vesicles of spherical

shape. They contain enzymes involved in lipid metabolism. The synthesis
of peroxisomal enzymes occurs in RER like secretory proteins.

Nonmembranous organelles and cytoskeleton

The cell contains, in addition to the membrane bound organelles, also

many nonmembranous structures from which the ribosomes have been al-
ready described. In addition, the cytoplasm contains also a set of filamen-
tous proteins in form of microfilaments, microtubules and intermediate fil-
aments. These filamentous proteins are attached to cell membranes to form
an internal three-dimensional scaffolding of the cell. They are responsible
not only for the form and shape but also for the movement of the cell, for
anchoring cells together, transport of material within the cytosol etc. The
microtubules can be arranged in bundles and form a special organelle-like
centriole, which plays an important role in the development of the micro-
tubular network in dividing cells and in motile cilia. The detailed composi-
tions of these structures follow in the next chapters.

Microtubules

These are present in all cells as hollow, unbranched structures, com-

posed of the protein tubulin. Each microtubule is 25 nm in diameter and is
composed of protofilaments of alternating alpha and beta tubulin subunits.
These subunits polymerize to form protofilaments which are arranged into
groups of 13 forming the hollow tubule. They are supporting elements of
the cell (analogous to the bones of the body), but they also participate in the
movement of certain components inside the cell (organelles, neurotransmit-
ters in axons, melanin in pigment cells etc.). Microtubules also represent
part of some organelles, like cilia, flagella, and centrosomes.

Centrosome (diplosome)

This is an organelle, present in both animal and plant cells, consisting

of a pair of centrioles. It represents an organizing center for polymeriza-

– 29 –
tion of microtubules in both normal and dividing cells. The centrioles are
cylindric structures (0.15 µm in diameter, 0.3–0.5 µm in length), com-
posed of 9 sets of microtubule triplets. The microtubules in a triplet are
closely stuck together, and the triplets are joined by protein links. In each
pair the long axes of the centrioles are situated at right angles to one anoth-
er. During mitotic cell division, a great number of microtubules arise and
radiate from centrioles, situated on both poles, to the chromosomes and
form the so called spindle apparatus. After cell division the microtubules
disappear.
Centrioles also serve as the basal bodies (kinetosomes) and site of origin
of epithelial cilia, and spermatozoal flagella.

Fig. 21 Centrosome and centriole

Microfilaments

These are slender rods about 7 nm in diameter, made up of the protein

actin in interaction with myosin. Actin is a globular protein (G-actin) which
polymerizes to form filaments (F-actin). In only half of cells does actin
appear in the form of filaments. The polymerization is under the control of
changes in calcium level, and the degree of polymerization is regulated by
various actin-binding proteins. The peripheral zone just beneath the plas-
malemma is rich in actin microfilaments, forming a sort of a cell cortex.
It is composed of a meshwork of actin and so called actin-linking proteins
(e.g., filamin, spectrin, ankyrin etc.).

– 30 –
Fig. 22 Actin filament as a part of the contractile apparatus

The microfilaments can form also bundles like in microvilli where the
actin is associated with fimbrin and fascin. In all cells actin microfilaments
interact with a protein myosin to generate the motile forces. The microfil-
aments of the muscle cells contain in addition to actin also troponin and
tropomyosin. The interactions of these molecules will be described in the
description of muscle tissue.

Intermediate filaments

In addition to the thin (actin) and thick (myosin) filaments cells also con-
tain intermediate sized cytoskeletal filaments of about 10–12 nm thickness,
anchored to transmembrane proteins at special sites on the cell membrane.
They are made of proteins which vary between different cell types and
functions.
In epithelial cells there are cytokeratins, forming usually a tough outer
layer (it is the main constituent protein of hair and nails). In muscle tis-
sue (smooth and striated) there is desmin. In tissues of mesenchymal origin
(e.g., embryonic undifferentiated cells) are characteristic vimentin filaments.
Neurofilaments form a part (next to microtubules and microfilaments) of the
neuron cytoskeleton. They also differ from the glial filaments (glial fibrillary
acidic protein – GFA), found in astrocytes. The nucleus of all cells contains
nuclear lamin, found on the inner side of the nuclear membrane.

Cell inclusions

These are the accumulations of metabolites or deposits of varied nature.

Proteins are stored in glandular cells as secretory granules and are released

– 31 –
periodically by exocytosis. Carbohydrates are stored in the form of the pol-
ysaccharide glycogen, seen in the electron microscope as coarse electron
dense particles mainly in hepatocytes and muscle cells. Fats (lipids) are
stored as non-membrane-bound vacuoles which appear as large clear spaces
mostly in the cytoplasm of adipose tissue cells.
The next category of cytoplasmic inclusions are the pigments. The red
iron-containing pigment hemoglobin in RBCs transports oxygen around the
body. In RBCs destroyed by macrophages hemoglobin becomes degraded
to two other pigments – brown hemosiderin (contains iron) and yellowish
bilirubin. The brown to black pigment of the skin, hair, eye and substan-
tia nigra of the brain is melanin. In tissues from elderly persons appears,
particularly in nerve, heart muscle and liver cells, a golden-brown pigment
lipofuscin. This “wear and tear” pigment resists digestion by lysosomal
enzymes and accumulates in the form of residual bodies in the cytoplasm
during ageing.

– 32 –
PART II: THE TISSUES

The tissues are assemblies of cells that share both their embryonic or-
igin and their morphological characteristics, and usually perform similar
functions. The term “Tissue” was first used in human anatomy by French
surgeon Marie Francois Xavier Bichat (1771–1802). In his books “Traité
des membranes” (1800) and “Anatomie générale” (1801) he classified and
described, without using a microscope, 21 tissues as basic morphological
and physiological units of an organism, as well as a subject of pathological
processes. At the present time, we know that despite its complexity the
human body is composed of only four basic types of tissue:

A. Epithelial tissue
B. Connective tissue
C. Muscle tissue
D. Nerve tissue

A. Epithelial tissue

Origin: all three germ layers, i.e. ectoderm, endoderm and mesoderm
Function: protection and secretion, absorption, respiration, excretion,
reception
Morphology: Epithelium is composed of closely aggregated cells (with
nearly no intercellular substance).
Epithelia line internal and external surfaces of the body or they are or-
ganized into structures of higher order (tubules, acini, trabeculae, etc.).
Each cell, then, has polarity: one surface, apical, is directed to the external
surface or lumen of a hollow organ, and the opposite surface, basal, is
oriented toward the underlying connective tissue (basement membrane).
Apical and basal surfaces often differ in their morphology and physiology.

– 33 –
Apical surface of epithelia

Microvilli – projections of the cytoplasm which enlarge the surface of

the cell. They appear mostly in cells responsible for absorption. They con-
tain actin microfilaments anchored in a terminal web (actin + myosin). At
the top of the villi is a glycoprotein glycocalyx. Accumulation of microvilli
is called a brush border.
Stereocilia – a variety of microvilli. These are long and branching fin-
ger-like nonmotile microvilli (not cilia!) in epididymis and in inner ear.
Unlike kinocilia, stereocilia do not have axonemes.
Kinocilia – these are motile processes 2–10 µm in length and 0.5 µm in
diameter. They possess a core of 9 pairs of microtubules surrounding two
central tubules (so called axoneme). The walls of two peripheral microtu-
bules in a doublet share 2–3 common protofilaments. The doublet tubules
are made of tubulin, while arms that extend from subfiber A are of the
protein dynein (a molecular motor that transforms chemical energy into
mechanical movement). Among the doublets are links composed of another
protein – nexin. The central pair of separated tubules is enclosed in a central
sheath and linked to the doublets by radial spokes.
The energy-dependent movements of cilia and flagella are induced by
sliding of adjacent doublets within the axoneme. The energy required for

Fig. 23 Microvilli

– 34 –
Fig. 24 Stereocilia and kinocilia

the sliding mechanism of axoneme bending is released from ATP through

the enzymatic activity of dynein (ATPase).

Basement membrane

is situated beneath epithelia (i.e., on the basal side) and formed by the
basal and reticular lamina. The basal lamina consists of a clear layer (also
called lamina lucida; 15 nm thickness, contains the multiadhesive glyco-

– 35 –
protein laminin) and a dense layer (lamina densa; 30–300 nm thick net-
work of very fine fibrils). In places where epithelial cells are in contact with
connective tissue, the basal lamina lies on the reticular lamina formed by
reticular and collagenous fibers.

Fig. 25 Basement membrane

Cell adhesion

The cell contacts created by cell junctions occur not only between epi-
thelial cells, but also in non-epithelial cells, enabling cell-cell communica-
tion (see, e.g., cardiac muscle of smooth muscle). This intercellular contact
is enabled by the cell adhesion molecules. There are two main groups of
adhesion molecules:

1. Calcium dependent molecules, including cadherins and selectins

2. Calcium independent molecules – these include the immunoglobulin
superfamily and integrins
Cadherins play a major role in cell adhesion and differentiation, estab-
lishing a link between the internal cytoskeleton of a cell and the exterior
of another cell. There are about 40 different cadherins. E-cadherin (epi-
thelial cadherin) appears along the lateral cell surfaces to mediate cell-cell
attachments in epithelial layers. They form dimers which bind to dimers of
the same class of cadherins in the opposite cell membrane (i.e. homophilic
interaction). N-cadherin is found in the CNS and in striated muscles.
Selectins are bound to carbohydrates, namely to a specific oligosaccha-
ride attached to a protein or a lipid. They belong to the lectin family and
participate in the migration of leukocytes from the blood stream into sur-
rounding tissue to reach the sites of inflammation and enable the homing
mechanism, i.e., to permit the T-lymphocytes to “home” in lymph nodes.

– 36 –
There are three major classes of selectins: P-selectin found in platelets,
E-selectin on activated endothelial cells and L-selectin on leukocytes.
Ig superfamily proteins mediate both homophilic and heterophilic
interactions, i.e., they can bind to identical molecules on another cell or
to other members of the family. Their cell adhesion molecule (CAM) is
folded into immunoglobulin-like domains. The best known is ICAM – i.e.,
intercellular cell adhesion molecule, which is expressed on the endothelial
surface and facilitates the transendothelial migration of leukocytes from the
bloodstream into the tissues. Others are VCAM – vascular cell adhesion
molecule, and NCAM – neural cell adhesion molecule. The surface marker
CD4 of T-helper lymphocytes also belongs to this Ig-superfamily.
Integrins are mainly involved in cell-extracellular matrix interactions.
Almost every cell expresses one or several integrins. The cytoplasmic do-
main of integrins is linked to actin filaments (through connecting proteins),
while the extracellular one binds to laminin and fibronectin (components
of basement membrane), which interact with various collagen types. The
relationship between integrin and extracellular matrix is important for cell
migration during embryogenesis. This process can be disrupted by small
peptides – disintegrins.

Fig. 26 Junctional complex

– 37 –
Junctional complex
The boundary between adjacent epithelial cells is formed by tight junc-
tions (zonula occludens) which form a belt around the cell and usually just
below them (more basal) are adherens junctions (zonula adherens) with
fine filaments which form a belt around the cell. Another important protein
complex at the cell-cell junctions is the desmosome (macula adherens) –
not in belts but in plaques – which are sites of local cell adhesion and
of attachment of the cytoskeleton (tonofilaments of cytokeratin). The last
component is the gap junction or nexus – this appears in plaques and me-
diates flow of current between cells through connexon protein molecules
arranged in hexamers passing through both cell membranes.

Covering epithelia

form a tissue with a protective function for external and internal surfaces
of the body. As in all epithelial tissues, blood vessels are absent; however,
nerve endings are present.

Simple epithelia
These form one layer of cells lying on a basement membrane.
Simple squamous epithelium is made up of one layer of flattened cells.
E.g., glomerular (Bowman’s) capsule of kidney. A modification of the sim-
ple squamous epithelium is represented by endothelium (lining of the whole
circulatory system) and mesothelium (lining of the body cavities). These
are called false or secondary epithelia because of their mesenchymal origin.
Simple cuboidal epithelium is made of cells like paving stones. E.g.,
thyroid follicles, sweat glands, intralobular ducts of salivary glands.
Simple columnar epithelium (cylindrical) is made of tall, prismatic
cells. The nucleus is usually closer to the basal part of the cell. E.g., alimen-
tary canal (stomach to rectum), uterus, oviduct.
Pseudostratified – a variety of simple columnar epithelium. A single
layer of cells which rest on the basement membrane but only the tallest
reach the surface. Cells are mostly ciliated. E.g., nasal cavity, trachea.

Fig. 27 Simple epithelia

– 38 –
Stratified epithelia
The cells are arranged in multiple layers, named according the form of
cells of the superficial layer.

Stratified squamous – basal layer is columnar, then polyhedral and to

the surface more and more flattened, i.e., squamous. They appear in two
types:
a) Stratified squamous keratinized: the upper horny layer contains dead
squamous cells (stratum corneum and stratum desquamans or disjunc-
tum), e.g., epidermis.
b) Stratified squamous non-keratinized: with no horny layer on the surface.
E.g. upper part of digestive system (mouth cavity to cardia of stomach),
vagina, cornea.

Fig. 28 Stratified squamous epithelia

Fig. 29 Stratified columnar epithelium

Stratified columnar – a very rare type. Deepest layer formed by cuboi-

dal cells, then come polyhedral and on the surface columnar cells. E.g.,
conjunctiva.

– 39 –
Fig. 30 Transitional epithelium (urothelium) in contracted and relaxed shape

Transitional – a variety of stratified epithelium. Allows deformation in

contractions and stretching. Superficial layer formed by “umbrella” cells
(often with two nuclei). Most of the cells are in touch with the basal mem-
brane, but the surface umbrella cells are losing this connection, thus making
a separate layer. Appears in urinary passages.

Glandular epithelia

The glands can be divided into exocrine which possess ducts and se-
crete onto an epithelial surface, and endocrine glands which are ductless
and secrete hormones into the bloodstream (they will be described in the
microanatomy part).

Exocrine glands
These consist of cells producing secretions (proteins, lipids, glycopro-
teins). The process of protein secretion proceeds in three steps.
1. Ingestion – amino acids from the bloodstream enter into the cytoplasm.
2. Synthesis – association of the amino acids with tRNA and their trans-
port to the ribosomes which move along the mRNA reading in codons
(3 nucleotides) the instructions (message from DNA). Amino acids are
inserted into the protein molecule being developed on the ribosome. The
ribosomes are attached to the membrane of endoplasmic reticulum in
which the newly formed protein molecules are released. Steps 1–2 are
common steps of protein synthesis in all cells. In glands, the following
third step is added.
3. Extrusion – the secretory product is transferred from RER to the Golgi
complex and in secretory vesicles moves to the surface and is extruded
by the process of exocytosis.
The secretory portion may be composed of one cell type – unicellular
glands (such as goblet cells in the respiratory epithelium and in the intes-
tine), or many cells organized into structures of various shapes – multicel-
lular glands.

– 40 –
Classification of exocrine glands according to shape
According the shape of the secretory units, the exocrine glands can be
categorized as tubular (the secretory portion is a straight or coiled tube), or
alveolar (also named acinar, the secretory portion is a wide outpouching,
having a shape of a flask or grape). An alveolus is very similar to an acinus
in its external shape, but alveoli have a wider inner lumen than acini. If the
tube ends in a sac-like dilation or if the gland contains tubules and alveoli
at the same time, the gland is tuboalveolar. If the duct is unbranched, the
gland is called simple, even if the single duct sometimes receives secretions
from several secretory units (which is called a simple branched gland then).
If the duct is branched into a system or hierarchically arranged ducts, the
gland is compound.

For example:
• simple alveolar glands do not occur in human

• simple acinar glands are, e.g., paraurethral glands outpouching from
the urethra
• straight simple tubular glands are, e.g., intestinal glands of the small

and large intestine (also known as the crypts of Lieberkühn)
• simple coiled tubular glands are the eccrine sweat glands of the skin

• simple branched tubular glands are, e.g., gastric glands (in the body
and the fundus of the stomach), or endometrial glands (in the uterine
mucosa)
• simple branched acinar glands are, e.g., sebaceous glands of the skin

• compound tubular glands are the submucosal glands of Brunner in
duodenum;

Fig. 31 Types of exocrine glands according to shape

– 41 –
• compound acinar gland is, e.g., the parotid gland or the exocrine por-
tion of the pancreas
• compound tuboalveolar (tubuloacinar) glands are, e.g., the sublin-

gual and the submandibular salivary glands.

Glands according to the mechanism of secretion

1. Merocrine (eccrine) glands: The secretory product is released in small
quantities by repeated exocytosis and the shape of the cell does not
change substantially. E.g., sweat glands, parotid, pancreas.
2. Apocrine glands: first, the apical portion of the cell accumulates the se-
cretion and then it is lost with the secretory product. E.g., large axillary
sweat glands. In mammary glands, the milk lipids are secreted by the
apocrine secretion, the proteins (casein) by the merocrine way.
3. Holocrine glands: The secretory product is accumulated in the cyto-
plasm and the secretion process results in a complete breakdown of the
dying cells. E.g., sebaceous glands.

Fig. 32 Patterns of secretion

Glands according to their secretory products

1. Serous – the cell body is basophilic due to the abundant rough endo-
plasmic reticulum. The cells produce watery secretions with proteins.
A serous cell contains rounded nucleus, abundant RER and zymogen
granules (i.e. secretory vesicles with temporarily inactive enzymes).
E.g., parotid gland, exocrine portion of pancreas.
2. Mucous – the cell cytoplasm is pale. The cells produce viscous mu-
cus. The nucleus is flattened on the cell base, the cytoplasm filled by
mucus-containing vesicles that have a high polysaccharide content and
therefore in routine methods stain only weakly or not at all. E.g., submu-
cosal duodenal glands of Brunner.

– 42 –
3. Seromucous (mixed) glands. Secretory units are composed from mu-
cous cells in tubular part of the gland. The serous cells are arranged in
acini, or they form a halfmoon-shaped cap of the acinus, named serous
demilune (of Gianuzzi). E.g., submandibular gland (mostly serous) and
sublingual gland (mostly mucous). Also the nasal cavity, larynx, trachea
and bronchi contain seromucous glands

Fig. 33 Serous and mucous cells

The ducts of compound glands, such as the parotid, submandibular or

sublingual glands, have the following parts:
1. Intercalated ducts are lined by squamous or cuboidal cells. Each inter-
calated duct drains a separate secretory unit.
2. Several intercalated ducts merge into intralobular ducts, that are still
surrounded by secretory units.
3. They open into interlobular striated ducts lined by columnar cells
with striations in the basal part, caused by infolding of the basal plas-
malemma and by elongated mitochondria (ion transporting cells). The
striation is not visible in pancreas.
4. These ducts join into interlobular ducts, the lining of which is stratified
cuboidal becomes finally stratified. Interlobular ducts merge into one or
several major excretory ducts.

– 43 –
Fig. 34 Seromucous gland in a section (left) and surface view (right)

Myoepithelial cells
These embrace the glandular alveoli or ducts like a basket and that
is why they are also called basket cells. They are situated between the
secretory or ductal cells and basement membrane. The cells contain actin
as well as myosin filaments and can contract and help to release the se-
cretory products. The myoepithelial cells are interconnected by gap junc-
tions and also contain cytokeratin filaments which prove their epithelial
character.

B. Connective tissue

Origin: mesenchyme
Function: connects cells, tissues and organs, supports the body, pro-
vides nutrition and defense
Morphology: Connective tissue consists of cells and extracellular ma-
trix composed of protein fibers and ground substance.
According to the consistency of the ground substance four chief types of
connective tissue can be recognized:

– 44 –
1. Connective tissue proper
2. Cartilage
3. Bone
4. Blood, lymph and tissue fluid

Connective tissue proper

Its main appearance corresponds to its function: to connect skin to the

underlying structures and to fill spaces between tissues and organs. Pos-
sesses a large amount of intercellular matrix in which many extracellular
fibers and bundles of fibers are embedded. There are relatively few cells,
which can be either fixed cells, that develop from the mesenchyme in the
connective tissue itself, or wandering cells, that develop from mesenchy-
mal hemopoietic stem cells elsewhere in the body and migrate into connec-
tive tissue proper by way of the bloodstream.

Cells
1. Fibroblasts represent the mother cells of connective tissue. The term
fibroblast is used for active stages with ability to proliferate and to pro-
duce significant amounts of extracellular matrix. Less active and resting

Fig. 35 Fibroblast and fibrocyte

– 45 –
 forms are called fibrocytes. The cells are usually spindle-shaped, with
an ovoid and pale nucleus with one or two nucleoli, rich rough endoplas-
mic reticulum, Golgi complex and elongated mitochondria. They do not
have phagocytic properties. Fibroblasts synthesize collagen, reticular
and elastic fibers, as well as ground substance.
Some modified fibroblasts mostly in wound sites contain bundles of ac-
tin filaments and dense bodies similar to smooth muscle cells. These
cells, called myofibroblasts, are implicated in wound contraction. Other
fibroblast-like cells are represented by reticular cells.
2. Reticular cells, which are similar to fibroblasts but differ from them by
their star-shaped form. They provide the framework of the lymphoid
and hemopoietic organs. The long processes contain tonofilaments
and are joined with the neighboring cell processes by desmosomes.
They produce reticular fibers which remain in close contact with them.
They contain free ribosomes, smooth endoplasmic reticulum and Golgi
complex.

Fig. 36 Reticular cell Fig. 37 Adipocytes

3. Fat cells, also named adipocytes, form white and brown adipose tissue.
White (or yellow) adipose tissue forms about 10% of the whole body
weight. This consists of unilocular adipocytes, spherical in shape and

– 46 –
 filled with one large fat droplet (not seen in the slide, because it has
been dissolved by the histological techniques). The cell has a signet ring
shape with a flattened and eccentric nucleus in a very thin layer of cyto-
plasm. There is only a little smooth ER and filamentous mitochondria.
Brown adipose tissue appears mostly in hibernating animals whereas in
other animals and in humans it is rare and located in interscapular region
and around the kidney, adrenals, aorta and neck. It is present in large
amounts in newborns and in adults it is gradually reduced. The cells are
multilocular and contain small droplets of lipids and a lot of mitochon-
dria which can produce 100 times more heat than other cells (under the
influence of norepinephrine).
4. Pigment cells, melanocytes, are of ectomesenchymal origin (i.e., de-
rived from neural crest). They are located usually at the dermo-epidermal
junction and enter between the basal cells of epidermis. They can have
various shapes and become branched with long cytoplasmic extensions
that ramify between the cells of deep epidermal layers (not connected
with them by desmosomes). They synthesize the pigment melanin in
membranous vesicles (parts of Golgi complex) called melanosomes.
The mature melanin granules are ellipsoid and can be transferred into
epidermal cells (keratinocytes). Although the number of melanocytes
is comparable among various human populations, their activity and
amounts of melanosomes may vary significantly, thus contributing to
the skin pigmentation.

Fig. 38 Melanocyte and mastocyte

– 47 –
5. Mastocytes (mast cells, heparinocytes) – the precursors of these cells
come from the mesenchymal cells of the bone marrow. Their name
comes from German word “Mast” which means fatten. They appear in
loose connective tissue along the vessels, intestine, thyroid gland etc.
They are large oval cells filled with many secretory granules, a small
nucleus, RER and Golgi complex. Granules contain heparin (sulphated
glycosaminoglycan – an anticoagulation factor) and histamine – a me-
diator of inflammation (increases the permeability of vessels and allows
the plasma proteins, e.g. immunoglobulins – to leak from them into the
tissues). The granules show a special staining property – metachroma-
sia – the granules are stained in a different color from the color of the
dye (e.g. toluidine blue stains purple instead of blue). They very much
resemble the basophils. They possess receptors for IgE on the cell mem-
brane and play a role in allergic reactions.
6. Macrophages – these cells, also known as tissue histiocytes, are related
to bone marrow precursors which mature into monocytes. The mono-
cytes migrate from the blood circulation in connective tissue and there
they can mature under the influence of immunoglobulins or the helper
type of T-lymphocyte into macrophages. They are usually round to oval
in shape and have an irregular and eccentrically placed, dark-staining
nucleus, well developed Golgi complex, RER and a number of phago-
somes and lysosomes. Their main function is phagocytosis. The antigen,
phagocyted by a macrophage (antigen presenting cell), becomes stored

Fig. 39 Macrophage and plasmocyte

– 48 –
 within a phagocytic vesicle. This vesicle fuses with a lysosome to be-
come a phagosome. The lysosomal hydrolytic enzymes break down the
antigen into small peptide fragments which bind to MHC molecules
(major histocompatibility complex) inserted in the phagosome mem-
brane. The phagosome fuses with the plasma membrane and the pep-
tide-MHC is exposed to T-lymphocyte, which then secretes interleu-
kins. Interleukins bind to B-lymphocytes and they increase their number
(after clonal divisions) and differentiate into plasma cells.
7. Plasma cells (plasmocytes) are the descendants of mesenchyme-derived
B-lym­pho­cytes that migrated in connective tissue. They are rounded in
shape, the nucleus is spherical, lies eccentrically and its chromatin shows
a “cart-wheel” effect (or clockface appearance), the nucleolus is large.
The basophilic cytoplasm is full of RER, ribosomes and Golgi complex,
mitochondria and secretory vesicles, all of which are critical for plasma
cells’ function, which is to synthesize and secrete the immunoglobulins
(humoral antibodies of all classes e.g. IgM, IgG, IgA, IgE etc.).
8. Some more originally mesenchymal cells are related to the loose con-
nective tissue, like endothelial cells (lining of circulatory system which
we discussed already in the chapter on Epithelial tissue) or pericytes
(perivascular cells which shall be mentioned in microanatomy of vessels).
In loose connective tissue also various types of blood cells can be found.

Extracellular matrix
This consists of fibers and an amorphous ground substance.

Fibers

There are three main types of protein fibers:

1. Collagen fibers – they appear white, unbranched, wide, wavy and stain
pink with eosin. They are firm and resist stretch. The fibers swell in acids
and alkalis, and when boiled they dissolve and yield gelatin (glue). They
can be digested by pepsin but resist trypsin.
In transmission electron microscope, the fibers appear striated (cross
striation) and show axial periodicity. They can be 1–20 µm thick. The
thickness depends on the amount of fibrils which form a collagen bun-
dle. The fibrils are conjoined with a protein substance and are about
0.3–0.5 µm thick. They consist of protofibrils (or microfibrils – 40 nm

– 49 –
 in diameter), containing tropocollagen molecules. Each molecule meas-
ures 280 nm in length and 1.5 nm in width, and it extends beyond its
neighbor by one quarter of its length. The overlapping regions cause
the axial periodicity. The collagen fibril formation is a self-assembly
process that occurs in the extracellular matrix.

Fig. 40 Assembly of a collagen microfibril, a fiber and a bundle of fibers

Collagen is the most abundant protein of our body (30% of the whole
body’s protein content). It is composed of three principal amino acids:
glycine, proline, and hydroxyproline. There are many types of colla-
gen – the most important are these five:
 Type I – produced by fibroblasts and osteoblasts, forms collagen
fibers, appears in loose and dense connective tissue and bones.
 Type II – produced by chondrocytes and appears in fibrils in hyaline
and elastic cartilage.
 Type III – produced by fibroblasts, smooth muscle cells and endothe-
lial cells, forms reticular fibers, appears in loose connective tissue,
arteries, liver, spleen, kidney, lung etc.
 Type IV – produced by epithelial and endothelial cells, muscle cells
and Schwann cells. Forms the basal laminae and basement mem-
branes.
 Type V – not well known – produced probably by fibroblasts and
appears in fetal membranes and bone.
2. Reticular fibers are fine and delicate fibers which branch and form
a supporting network. They are argyrophilic (stain by silver) and appear
around the vessels, nerves, muscles, adipose cells, alveoli, in basement
membranes, lymph nodes, spleen, glands etc. They do not swell in acids
and when boiled they do not give gelatin. Most fibers in fetal connective
tissues and in healing wounds are of the reticular type, considered as
immature collagen fibers and called precollagenous, and they are grad-

– 50 –
 ually replaced by collagen fibers. Reticular fibers are made up of narrow
bundles of fibrils with the periodic structure typical of collagen. They
contain more hexoses than in collagen (this is the reason for being able
to reduce silver cations to black atomic silver). Although reticular fibers
are considered a separate type of fiber, they are actually composed of
type III collagen.
3. Elastic fibers are yellow, long, thin, homogenous, non fibrilar and
branched fibers but also membranes. They are 0.5–4 µm thick. They
appear, e.g., in yellow ligaments, vagina, elastic cartilage, and in blood
vessels, where they also occur in form of fenestrated membranes. They
can be stained by orcein or resorcin-fuchsin. They can not be digested
by trypsin but elastin can be hydrolyzed by pancreatic elastase, they do
not yield gelatin and are resistant against acids and alkali. They con-
sist of amorphous protein elastin in the central region, surrounded by
microfibrils (structural glycoprotein subfibrils of 10 nm). In addition to
glycine and proline elastin contains also desmosine and valine amino
acids, which form hydrophobic domains that are responsible for elastic
coiling of the molecules.

Fig. 41 Reticular fibers and elastic fibers

Ground substance
The amorphous jelly-like substance in which the cells and fibers are em-
bedded. It is derived from connective tissue cells and its consistency is liq-
uid – a loose gel. Chemically it is a protein-polysaccharide complex, i.e.

– 51 –
glycoprotein, formerly called mucopolysaccharide. There are two groups
of glycoproteins:

1. Glycosaminoglycans are complex substances of a carbohydrate nature

consisting of a hexosamine + uronic acid combined with protein. Two
main kinds are:
Hyaluronic acid consists of glucosamine + glucuronic acid with about
2% protein only. Forms intercellular substance of fetal and adult tissues
(umbilical cord, vitreous humor of the eye, synovial fluid and cartilage).
Represents a barrier against bacteria (however, some bacteria posses
enzyme hyaluronidase that depolymerizes the acid, thus facilitating the
spreading of infection through the extracellular matrix).
Sulphuric esters of glycosaminoglycans The most known is chondroi-
tin sulfate – consists of galactosamine + glucuronic acid with about
20% protein. Appears in cartilage, bone, cornea, skin, notochord etc.
Similar are: dermatan sulphate (skin, tendon), heparan sulphate (lung,
liver, basal laminae) and keratan sulphate (cornea, intervertebral discs).
2. Structural glycoproteins are predominately protein to which carbohy-
drates are attached. They are responsible for cell adhesion.
Fibronectin is synthesized by fibroblasts and epithelial cells. Binds
cells, collagen and glycosaminoglycans.
Laminin appears in basal laminae. Responsible for adhesion of epithe-
lial cells to basal lamina.
Chondronectin appears in cartilage. Responsible for adhesion of chon-
drocytes to collagen.

The types of connective tissue proper

1. Loose connective tissue (the cells of the ground substance predominate)
Mesenchyme – nonspecialized embryonic connective tissue contains
mesenchymal cells and reticular fibers.
Mucoid connective tissue – star-shaped fibroblasts and jelly-like inter-
cellular matrix. Umbilical cord (Wharton jelly), dental pulp, iris.
Collagenous connective tissue – fills spaces between tissues and or-
gans. Consists of fibroblasts, fibrocytes and all wandering types of cells,
collagen and elastic fibers. Appears in mucous membranes and in sub-
mucous layers.
Adipose tissue – adipocytes and reticular fibers. White adipose tissue
appears around the kidney, adrenal, mesentery, deep layers of skin (pan-

– 52 –
Fig. 42 Mesenchyme and loose connective tissue

niculus adiposus). Brown adipose tissue in fetuses, newborns and in-

fants. Also present in hibernating animals.
2. Dense connective tissue (the fibers predominate)
Irregular – collagen fibers form a felt structure (rare elastic and reticu-
lar fibers). Appears in dermis and fibrous capsule.
Regular – including tendons, where collagen fibers form primary bun-
dles (between are fibroblasts). Aponeuroses have the same structure but
in flat sheets. Ligaments are elastic connective tissue (elastic and colla-
gen fibers, appear in vertebral column, e.g., yellow ligaments).

Fig. 43 Regular dense collagenous (left) and elastic (right) connective tissue

– 53 –
Cartilage

Cartilage is a semirigid supporting tissue with a firm intercellular matrix.

Related to its supporting function it is closely associated with bones which
mostly develop on the basis of a cartilaginous model. Most of the fetal
skeleton is formed from cartilage. Genetically (mesenchymal origin) and
morphologically it corresponds to the connective tissue. Boiled cartilage
yields glue.
Cartilage consists of cells (chondrocytes) and intercellular matrix
(ground substance and fibers). Mature cartilage lacks blood vessels. There
are three slightly different subtypes of cartilage.

Hyaline cartilage
It is of white appearance in the fresh state. It forms most of the fetal skel-
eton. In postnatal life: articular cartilages of joints, costal cartilages (ventral
ends of ribs), cartilages of the nose, larynx, trachea, bronchi.
Hyaline cartilage occurs usually in plates covered with a vascular fi-
brous membrane, i.e. perichondrium (missing in the articular cartilage
in joints). Perichondrium contains fibroblasts, collagen fibers and many
vessels which do not penetrate into the matrix. The inner part of the peri-
chondrium forms a chondrogenic layer with chondroblasts which produce
intercellular matrix. The chondroblasts buried in cartilage matrix mature
into chondrocytes. The daughter cells remain in matrix cavities – lacu-
nae – and form cell nests – isogenous groups. The wall of a lacuna thick-
ens in a more basophilic capsule which represents a deposit of chondroitin
sulphate produced by the chondrocytes. In addition to proteoglycans the
chondrocytes produce type II collagen and chondronectin. They contain
protrusions and organelles for protein synthesis (RER). The saccharides
and sulphates are incorporated in Golgi complex where they are combined
with proteins to form mucopolysaccharides of the matrix. The chondro-
cytes are nourished by fluid exchange with matrix (from blood vessels in
perichondrium).
The intercellular matrix stains with basic dyes. It is formed by chon-
dromucoproteins (mucoprotein + chondroitin-sulphate). It contains a dense
network of fine collagen fibers. They can not be seen in normal slides be-
cause they have the same refractive index as the ground substance, but
can be demonstrated by silver impregnation or by digesting the tissue with
trypsin.

– 54 –
Fig. 44 Hyaline cartilage and chondrocyte

Elastic cartilage
is adapted to repeated bending. It appears in epiglottis and external ear.
It resembles hyaline cartilage but contains in addition to collagen fibers an
amount of elastic fibers (can be demonstrated by orcein or resorcin-fuch-
sin). There is perichondrium on the surface and the chondroblasts and cho-
drocytes produce all components of the matrix, including elastin. The cells
are embedded in lacunae and do not form so frequently, as in hyaline carti-
lage, small isogenous groups.

– 55 –
Fibrocartilage
This tissue is transitional in form between dense connective tissue and
hyaline cartilage. Appears in places of tendon insertions, pubic symphysis,
intervertebral discs and intraarticular menisci. It possesses no perichon-
drium, and contains small amount of matrix among abundant and thick
bundles of collagen fibers, which form irregular bundles or are arranged in
parallel and sandwich the chondrocytes.

Fig. 45 Fibrous cartilage

Bone

Bone represents a variety of connective tissue, the ground substance of

which is impregnated with calcium salts (97% of the calcium in the whole
body). Apart from the rare fibrous bone which appears in dental cement
and bony tuberosities only, most of the skeleton is formed by lamellar
(Haversian) bone, where layers of osteocytes are found between the lamel-
lated bone matrix. Therefore, lamellar bone is made up of layers (lamellae,
plates) of calcified interstitial substance.
The bone cells, osteocytes, are situated in lacunae, connected in a con-
tinuous system by bone canaliculi. Osteocytes send their processes which
are joined to those of other osteocytes via gap junctions. They possess re-
duced rough endoplasmic reticulum and Golgi complex and condensed
chromatin.
The bone matrix contains calcium and phosphorus in the form of hy-
drated hydroxyapatite [Ca10(PO4)6(OH)2].nH2O crystals and amorphous cal-
cium phosphate Ca3(PO4)2. The organic substance is of type I collagen and

– 56 –
Fig. 46 Osteocytes

glycoprotein ground substance. The collagen fibers run in parallel, oriented

in neighboring lamellae in different directions.
All bones are lined on both external and internal surfaces by dense con-
nective tissue – periosteum and endosteum, both containing osteogenic
cells. Both epiphyses of a long bone are covered by an articular hyaline
cartilage (with no perichondrium).
Two kinds of lamellar bone exist, namely the spongy bone and the com-
pact bone.

Fig. 47 Long and flat bone

– 57 –
Spongy (cancellous, trabecular) bone
It consists of bony trabeculae and spicules with large spaces among them
(which contain bone marrow). This type of bone appears in epiphysis of
long bones, diploe of flat bones, in ribs and vertebral bodies.

Fig. 48 Spongy bone

Compact bone
Compact bone forms dense bony tissue with lacunae and narrow can-
aliculi (which contain osteocytes with processes). In the compact bone the
lamellae are concentrically arranged to form osteons (Haversian systems).
The diaphysis (and lateral part of epiphysis) is covered by periosteum
which consists of an outer fibrous layer (collagen fibers and fibroblasts)
and inner osteogenic layer (spindle shaped osteoprogenitor cells, which
develop in osteoblasts).
Periosteum becomes fixed to bone by strong collagenous fibers which
penetrate into the bone – Sharpey’s fibers. The inner surface of bone
marrow cavity is lined by thin connective tissue which contains one layer
of osteoprogenitor cells – endosteum. The function of these membranes
is nutrition (penetration of blood vessels into the bone through Volk-
mann’s canals) and production of new osteoblasts for growth and repair
of bone.
The bone lamellae underneath periosteum and endosteum are arranged
concentrically, forming outer and inner circumferential lamellae. Be-
tween these peripheral lamellae many osteons (Haversian systems) are situ-
ated. These systems are formed by 4–20 concentric lamellae which contain
the osteocytes. These cells are interconnected by their processes, through

– 58 –
Fig. 49 Compact bone

the canaliculi. In the center of each system a Haversian canal contains

blood and lymphatic vessels, nerves and some connective tissue. Among
the Haversian systems are irregular (triangular) groups of parallel lamellae
called interstitial lamellae, as remnants of destroyed systems during the
growth of the bone.

Fig. 50 Osteon

– 59 –
Fig. 51 Section of compact bone showing the lamellas of an osteon

The matrix of the lamellae, i.e. intercellular substance of bone, is im-

pregnated with insoluble calcium salts (amorphous calcium sulfate, hy-
droxyapatite crystals). This inorganic part forms about 50% of the whole
matrix. Organic matter contains twice as much collagen (type I) than in
the matrix of a hyaline cartilage. The collagen fibers are oriented in paral-
lel in each lamella, but in neighboring lamellae in different directions, to
enable the bone to withstand bending, twisting etc. The amorphous ground
substance contains glycosaminoglycans (chondroitin sulfate and keratan
sulphate). There is a difference between calcification (deposition of calci-
um salts in any tissue) and ossification (process of bone tissue formation).

Ossification
Ossification means the process of bone histogenesis. Some bones de-
velop directly from mesenchyme (i.e., embryonic connective tissue). This
process is named intramembranous ossification. In that way the bones
of face, cranial vault, definitive mandible (embryonic lower jaw is formed
by Meckel’s cartilage which does not ossify) and clavicles develop. But
the majority of bones develop on the basis of a cartilaginous model, which
becomes replaced by bony tissue – endochondral ossification. The histo-
genic process is very similar: the transformation of embryonic connective
tissue i.e., mesenchyme into the bone by the activity of osteoblasts.

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Intramembranous ossification
The primitive connective tissue becomes richly vascularized, the cells
multiply and form reticular and collagen fibers. The young fibroblasts in-
crease in size, and form clusters (bone blastema). They differentiate, be-
come polyhedral and arranged in rows, and they are transformed in oste-
oblasts. These cells are basophilic, with GER and Golgi apparatus. They
produce an enzyme-alkaline phosphatase which hydrolyses calcium phos-
phoric ester (circulating in the blood) to form free salts – calcium phos-
phate. The original matrix has been replaced by a new interstitial substance
which is only slightly calcified – osteoid. The osteoblasts divide and their
daughter cells become embedded in the ground substance – these are the
osteocytes (less basophilic, less GER and Golgi apparatus). In that way the
first trabecules of primary bone have been formed.

Fig. 52 Intramembranous ossification

Fig. 53 Primary bone trabeculae

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 These trabecules are rapidly absorbed by the activity of multinucleated
cells of macrophage type – osteoclasts. They are motile, branched, and
slightly eosinophilic with many lysosomes. Most probably develop by fu-
sion of monocytes and they secrete proteolytic enzymes responsible for
the bone resorption. The cavities produced by this resorption are called
Howship’s lacunae. Simultaneously new bone lamellae are laid down by
the activity of the next wave of neighboring osteoblasts.

Endochondral ossification
This is the process in which the hyaline cartilage degenerates to be re-
placed by bone. It has several stages. The whole process and histological
changes during the endochondral ossification can be summarized as fol-
lows:

1. Swelling of cartilage cells in the center of the cartilaginous structure

(due to lack of nutrition) and arrangement of the chondrocytes into rows.
2. Development of the collar bone around the diaphysis (intramembranous
ossification on the basis of connective tissue of the perichondrium).
3. Calcification of the cartilage matrix – formation of the primary ossifi-
cation center.
4. Invasion of a vessel with mesenchymal cells from the perichondral
(now remodelled into periosteal) tissue.
5. Resorption and excavation of the calcified cartilage by the chondro-
clasts (now becoming osteoclasts, i.e. macrophages of vessel mesen-
chyme origin) and formation of the primitive marrow cavity.
6. The branches of vessels continue to phagocytose (along a line of ero-
sion) the degenerated cartilaginous cells situated in the zone of hyper-
trophy and calcification. These cells are replaced from the zone of pro-
liferation and maturation, which develop from the resting cartilage in the
epiphyseal plate.
7. Mesenchymal cells of the vessel develop into the cells of primitive mar-
row and are then transformed into osteoblasts.
8. Osteoblasts lay down the ground tissue (osteoid) in which their daughter
cells become embedded as osteocytes.
9. Destruction of this newly formed primary bone by osteoclasts and
excavation of Howship’s resorption lacunae (see intramembranous
ossification), around which the circularly arranged lamellae develop
(osteons).

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Fig. 54 Principles of endochondral ossification

In an epiphyseal growth plate, the following zones of endochondral

ossification can be distinguished:

1. The resting zone of normal hyaline cartilage

2. The proliferation zone of rapidly dividing chondrocytes, which are ar-
ranged into columns.
3. The hypertrophic zone of enlarged chondrocytes

– 63 –
4. The calcification zone, where the cartilage matrix is provisionally calci-
fied by mineral salts.
5. The erosion zone, where the chondroclasts destroy the cartilage, thus
making space for new bone tissue
6. The ossification zone, where primary bone trabeculae are formed by
osteoblasts.

Fig. 55 Zones of endochondral ossification (upper scheme) and cross section showing
the penetration of blood vessels into an ossification center (lower scheme)

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Tooth

The tooth represents a complex structure which consists in addition to

the soft pulp of three different hard tissues: dentin, enamel and cement.
Even though the enamel does not correspond to the criteria of the connec-
tive tissue (because of its ectodermal origin), we present in this chapter
the description of all these integrated tissues together. To understand the
structure of the tooth we have to describe at least the principles of its de-
velopment.

Development of the teeth

The first sign of tooth primordium appears at about 6 week of pregnan-
cy as a thickening of the oral ectodermal epithelium which proliferates
and forms a bud. This tooth bud is accompanied by the condensation of
the surrounding mesenchymal cells (i.e. ectomesenchyme, of neural crest
origin). Therefore, the epithelial-mesenchymal interactions are the most
important processes of tooth development, which can be characterized as
a history of interactions between ectodermal epithelial cells, from which
the enamel-depositing ameloblasts develop, and neural crest-derived ec-
tomesenchymal cells, from which dentin-depositing odontoblasts develop.

These processes are under the control of specific (MSX) homeobox

genes, which then activate a cascade of molecular changes, leading to the
expression of various adhesive molecules (syndecan, tenascin, fibronectin,
growth factors etc.) involved in early tooth development.
The proliferation of the oral epithelium forms a continuous horse-
shoe-shaped dental lamina in both jaws. Shortly after its formation, the
dental lamina shows on each side of the jaw five regions of intensive mitot-

Fig. 56 Primordia of two dentitions

– 65 –
ic activity, representing the future primordia of the deciduous teeth (2 inci-
sors, 1 canine, and 2 molars).
The first bud stage is followed by the cap stage. The ectodermal part
forms the enamel organ in which the stratified epithelium becomes sub-
divided into flattened outer and high inner enamel epithelium (preamelo-
blasts). The epithelial cells between these layers become more and more
reticulated. The underlying mesenchyme cells are condensed in the dental
papilla, with the cells on its surface, forming a layer of preodontoblasts.

Fig. 57 Early stages of tooth development

The enamel organ becomes surrounded by the condensed mesenchyme,

called the dental follicle (sac). On the labial side of each enamel organ the
remainder of the dental lamina produces solid epithelial buds of permanent
teeth (10–12 week). These are the 20 counterparts of the deciduous teeth.
The dental lamina then extends gradually backwards and the remaining 3
germs of permanent teeth are formed (the primordia of the last two molars
are not formed until after birth).
During the next bell stage the inner epithelium of the enamel organ dif-
ferentiates into ameloblasts which deposit the enamel matrix. The produc-
tion of enamel occurs only in the future crown region under the influence
of the stellate reticulum which fills the gap between the both enamel epi-

– 66 –
Fig. 58 Bell stage of tooth development

Fig. 59 Enamel organ

thelia. Ameloblasts project on their base into conical extensions – Tomes’

processes (with numerous secretory granules) which are sites of secretion
of the enamel matrix. This matrix is composed of unique enamel proteins
which direct the mineralization of enamel into the hardest tissue in the

– 67 –
body. After the end of secretory phase, the ameloblasts regulate the matu-
ration of enamel, and they degenerate during tooth eruption.
The preodontoblasts of the dental papilla differentiate into odonto-
blasts, which secrete procollagen, which then matures in collagen fibrils
of predentin. Mineralization of these fibrils results in formation of dentin.
Dentin resembles bone in its composition although the histological appear-
ance is different, as the secretory odontoblasts do not get incorporated into
the dentin matrix. Each odontoblast sends its cytoplasmic process – Tomes’
fiber, which becomes embedded in dentin and contributes to the formation
of dentin tubules. Odontoblast cell bodies remain as a confluent cell layer
between the dentin and the cells of dental pulp. At this stage also the nerve
fibers enter the papilla.
After the enamel organ has formed the enamel of the crown, both sheets
of its enamel epithelium grow down into the future root area. They form
a two-layered epithelium because they are not separated by stellated epithe-
lium, which cannot therefore perform its enamel inductive potency in the
root region; instead, the inner enamel epithelium has retained its general
potency to initiate the differentiation of the dentin forming odontoblasts
on the pulp surface. This epithelial root sheath (of Hertwig) is a simple
tubular structure in case of a tooth with a single root. In multi-rooted teeth
this simple tube becomes subdivided into separate tubes, depending on the
number of roots. This is achieved by the inward growth of horizontally di-
rected processes of epithelium from the epithelial root sheath, which meet,
fuse and produce separate, epithelial surrounded parts of the subdivided
root pulp with odontoblasts.
The epithelial sheath breaks gradually up (the remnants of it are known
even long after tooth eruption as rests of Malassez) and the newly formed
dentin induces the differentiation of cementoblasts from the surrounding in-
ner layer of the dental follicle. These cementoblasts form then the cement –
the fibrous bone covering the root. The middle layer of the follicle develops
in the periodontal ligament and the outer one in the alveolar bone.

Histology of the tooth components

Enamel
This is the most highly calcified and hardest tissue of the body. It con-
sists almost entirely of calcium salts (95% hydroxyapatite) and only 0.5 %
comprises organic substances, produced by ectodermal ameloblasts (pro-

– 68 –
teins amelogenin and enamelin). The enamel consists of some million
slightly flattened hexagonal rods or prisms, oriented perpendicular to the
dentine surface, and having a wavy arrangement. The bends of the rods in
two neighboring zones cross one another. The crossings of groups of rods
appear as light and dark lines – the Hunter-Schreger bands. They are
curved with the convexity rootwards and occupy about two thirds of the
enamel thickness. Other bands – incremental lines (of Retzius) – represent
the former outline of the enamel at succeeding stages of its formation. The
free surface of the enamel is covered by a thin primary enamel cuticle
(named also Nasmyth’s membrane), which represents the final product
of ameloblasts.

Fig. 60 The tooth

– 69 –
Fig. 61 Formation and structure of the enamel

Dentin
Forms the bulk of the tooth substance and gives the basic shape to each
tooth, and is yellowish in color. It is less hard than enamel, but harder than
either bone or cement. It consists of an organic (20% – most of it collagen)
and an inorganic (80%, mostly hydroxyapatite crystals) part. It has a radi-
ally striated appearance because of minute canals, the dentinal tubules,
which radiate from the pulp cavity, curving and branching toward the pe-
riphery. The layer of dentin immediately surrounding each tubule is more
refractive and is called the lamina limitans (also sheath of Neumann).
The tubules are penetrated by cytoplasmic processes (Tomes’ fibers) from
the odontoblasts, situated outside the dentin on the surface of the pulp. The
odontoblastic process with some smaller lateral branches extends through
the unmineralized predentin before it enters into tubular channels in the
mineralized dentin.
The calcifying inorganic element of the dentin appears in the organic
matrix as globules (calcospherites) which fuse to form a homogenous sub-
stance. In some areas near the amelo-dentinal junction the globules may
not fuse and the organic matrix remains uncalcified. It forms mainly in the
crown region a layer of interglobular dentin, which appears black in dried
sections as so called interglobular dentin spaces (lacunes of Czermak).

– 70 –
Fig. 62 Odontoblasts

Fig. 63 Dentin

A similar layer of granular appearance can be seen immediately beneath the

cement and is known as Tomes’ granular layer.

Cement
The cement covers the whole root of a tooth as a thin layer of a fibrous
bone. It is yellowish in color and less hard than dentin. It is composed of an

– 71 –
organic matrix and of an inorganic element. The organic matrix consists of
collagenous fibers embedded in an amorphous cementing substance which
contains acid mucopolysaccharides. The inorganic element is represented
by calcium salts in the form of apatite molecules. It is deposited as submi-
croscopic crystallites in the cementing substance among collagenous fibers.
Two types of cement are recognized depending on the presence or ab-
sence of cells – acellular (primary) and cellular (secondary) cement, depos-
ited in layers. Deposition of cement continues throughout life. Acellular
cement forms the innermost layer of cement and consists of layers of col-
lagen fibers (Sharpey’s fibers) formed by the fibroblasts of the periodontal
membrane. The cellular cement is mostly found at the apical region of the
root. The cells – cementocytes – are irregularly distributed. They lie in
spaces – lacunae – like the osteocytes in bone. The processes of cemento-
cytes penetrate in fine canaliculi and often anastomose with those of other
cells. In both acellular and cellular cement incremental lines run roughly
parallel with the root surface and represent intervals between successive
depositions of cement.

Periodontal membrane
Consists of bundles of collagenous fibers which pass from the cement to
the periosteum of the tooth alveolus, to adjacent teeth or into the gingival
tissue surrounding the tooth. These fibers are known as the principal fibers
of the periodontal membrane and are bound together by a cementing sub-
stance. They can be divided into groups according to the direction in which
they run or according to their function. Oblique fibers are most common
and run obliquely inward to the root. In the region of the neck the fibers run
horizontally and form a cervical group. From the neck of the tooth a group
of fibers pass to the very rim of the socket and are known as the alveolar
crest fibers. Another group of fibers also run from the neck radially into the
overlying gum as gingival fibers.

The pulp
It occupies the central cavity of each tooth and consists of loose connec-
tive tissue, on the surface of which is a layer of the highly differentiated
cells – odontoblasts. They are tall columnar cells with an oval nucleus on
their base, rich granular endoplasmic reticulum, Golgi complex and mito-
chondria. Each odontoblast has a long cytoplasmic process (Tomes’ fiber)
which passes into the tubule of the predentin and traverses the whole thick-

– 72 –
ness of the dentin. Immediately beneath the odontoblast layer is a cell-free
zone (basal zone of Weil).
The subodontoblastic pulp contains spindle shaped fibroblasts, smaller
undifferentiated mesenchyme cells, as well as macrophages. In the ground
substance of the pulp containing glycosaminoglycans are fine and irregu-
larly arranged collagen and fibrils. The thicker fibers, which pass the od-
ontoblastic layer (mostly during the dentinogenesis stage), and mingle with
the thin fibrils of the pulp, are known as the Korff fibers. We can also find
reticular fibers in the vicinity of cells, but no elastic fibers. The whole pulp
is highly vascularized and innervated. The nerves and vessels enter the api-
cal foramen together and form numerous branches in the pulp. Some nerve
fibers lose their myelin sheath and form underneath predentin a marginal
plexus, branches of which, sensitive to pain, can enter the dentinal tubules
for some distance.

Alveolar bone and gingiva

Alveolar bone is that part of the facial skeleton of upper and lower jaws
which forms the alveoli and is in immediate contact with the periodontal
membrane. It is made up of a surface cortical layer of dense bone and
interior zone of cancellous bone. It differs from the typical bone because
the collagen fibers are not arranged in the lamellar pattern, but appear in
bundles which penetrate from the bone through the periodontal membrane
into cement.
The gingiva is a mucous membrane bound to periosteum of the jaws.
It is covered by stratified squamous epithelium, which is attached to the
crown by means of a cuticle which forms the epithelial attachment. It
represents the union of the mouth epithelium with the epithelial derivative
enamel. Between the enamel and the epithelium is a small deepening – the
gingival sulcus.

Blood

Blood consists of a fluid called plasma in which float the formed ele-
ments of the blood. The formed elements are: erythrocytes, leukocytes and
blood platelets.
Blood forms about 7–9% of body weight, which corresponds to a vol-
ume of approx. 5–6 litres in an average adult. Its pH is regulated to stay
within the narrow range between 7.36 and 7.44.

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 The proportion of blood occupied by formed blood cells is called hema-
tocrit (HCT, or packed cell volume, PCV) and is normally about 45%. The
remaining 55% of blood volume is occupied by the plasma.

Plasma
Plasma is the liquid extracellular material that transports the nutrients
and products of metabolism. It contains about 90% water and 7% proteins
(albumins, globulins, fibrinogen) and the rest include inorganic salts, lipo-
proteins, vitamins and hormones. Plasma that lacks coagulation factors is
called serum.

Erythrocytes
Erythrocytes, i.e. red blood cells (RBCs) are actually not complete
cells – during development in humans and in all mammals (not in other ver-
tebrates!) the nuclei are lost. Most of the other organelles are lost as well,
which results in no protein synthesis capability. The absence of mitochon-
dria means that the erythrocytes must use anaerobic methods to produce
ATP. The RBC count in adults ranges between 3.8–5.2 million/1 microliter,
i.e. per 1 mm3 in female, and 4.0–5.8 million/1 mm3 in men. There are
approximately 25 billion RBCs in the whole body and their total surface is
about 3 500 m2. In a newborn there are about 6.8 million/microliter (within
one week this falls back to 6 million), in an 11- year-old 5.5 million.
They are of biconcave shape of 7.2–7.8 µm in diameter, and about 2.6
thick in the periphery and 0.8 µm thick in the center. In fresh conditions,
the upper range of the diameter is true, but in a peripheral blood smear on
histological slides, the diameter observed is slightly smaller. In hypotonic
solution RBCs swell and undergo hemolysis (isotonic solution is approx.
0.85% NaCl). RBCs greater than 9 µm are called macrocytes, less than
6 µm are microcytes.

Fig. 64 Erythrocyte

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 RBCs contain 60% water and 33% conjugated protein – hemoglobin,
the remainder consists of other proteins and lipids. Hemoglobin (15 g Hb
per 100 ml in average) is a chromoprotein which consists of globin (a sul-
phur-containing protein) and heme (an iron-containing pigment – feropro-
toporphyrin). It is able to combine with oxygen to form oxyhemoglobin and
to release oxygen in tissues – reduced hemoglobin (carbaminohemoglobin).
The RBC plasmalemma contains about 40% lipids, 50% proteins and
10% carbohydrates. Half of the proteins are integral proteins. On the exter-
nal surface are oligosaccharides which determine the blood groups.
The life span is about 100–120 days. The old RBCs are removed by
macrophages of the spleen, liver and bone marrow.
The young RBCs which contain remnants of some organelles (but no
nucleus!) are called reticulocytes (about 1% of all RBCs in circulation).
They remain in blood circulation for 24 hours. If they contain remnants of
nucleus (DNA), they are called Howel-Jolly bodies (1–2 granules).

Leukocytes
The white blood cells (WBCs) are classified into 2 groups according the
presence and type of granules in their cytoplasm: granulocytes (polymor-
phonuclear leukocytes) which possess specific granules and agranulocytes
(mononuclear leukocytes) with no specific granules.

Granulocytes

Fig. 65 Neutrophilic, eosinophilic, and basophilic granulocytes

White blood cell differential count (all WBCs=100%)

Granulocytes Agranulocytes
Neutrophils 45–70% Lymphocytes 20–45%
Eosinophils 0–5% Monocytes 2–10%
Basophils 0–2%

– 75 –
Neutrophils
Count: 45–70% of WBC
Size: 12–15 micrometers in diameter
Life span: in blood several hours, in connective tissue 1–4 days. They
develop in myeloid tissue of bone marrow and at maturity are released in
the blood circulation.
Nucleus: consists of 2–5 lobes, connected with delicate strands, con-
tains coarse chromatin densely packed, stains deeply blue with basic dyes.
No nucleolus is visible. In female a drumstick-like appendix on one of
the lobes (Barr-body, inactivated X-chromosome) appears in about 3% of
nuclei of neutrophils.
There are 3 lobes in average – Hynek’s nuclear figure = 2.7 (e.g., num-
ber of lobes in 100 neutrophils divided by 100).
The Arneth formula is a useful concept used for assessing the average
age of the population of neutrophils in an individual. The neutrophils are
arranged according the number of their lobes from immature nonsegmented
“bands” to overmatured 5 lobes. A left shift means prevalence of young
neutrophils (less than 3 lobes) and often occurs as a part of reaction to bac-
terial infection. A right shift denotes prevalence of older neutrophils (more
than 3 lobes) in circulation and may indicate e.g., insufficient formation of
new cells in the bone marrow.

Arneth formula
Nuclear 1  2  3  4 5
lobes
[%] of neu- 5 35 41 17 2
trophils
left shift ← mean nuclear figure (2.7) → right shift

Cytoplasm: occupies more space than nucleus and contains a few ribo-
somes, GER, mitochondria. Two kinds of granules:
1. Fine specific granules of lavender (pink) color. They are neither acido-
phil nor basophil and contain alkaline phosphatase
2. Larger azurophilic granules of purple color. They are primary lyso-
somes and form about one third of all granules.
Function: First line and fast defense against antigens. Neutrophils can
move and migrate during the inflammation process from vessels into tis-

– 76 –
sue due to chemical attraction (chemotaxis). They are microphages, they
phagocytose bacteria and destroy the microorganisms by hydrolytic en-
zyme named lysozyme. Thus the contribute to formation of pus, which
consists of dead neutrophils, macrophages, microorganisms and cell debris.

Eosinophils (oxyphils, acidophils)

Count: 0–5% of WBC
Size: 12–15 micrometers in diameter (slightly larger than neutrophils)
Life span: about 8–17 days
Nucleus: two lobes connected with a thin chromatin bridge. Chromatin
is not so densely packed as in neutrophils.

Fig. 66 Eosinophilic granule (0.3–1.0 µm)

Cytoplasm: apart from a few mitochondria, contains large eosinophilic

granules (about 200 in one cell). Granules are lens-shaped – with a cen-
trally situated crystalloid core (containing basic parasite-killing proteins),
surrounded by externum (containing acid phosphatase).
Function: they are attracted (amoeboid movement) to sites where anti-
gens and antibodies react together and phagocytose antigen-antibody com-
plexes. They neutralize foreign proteins and are found in allergic reactions
and parasitic diseases (eosinophilia).

Basophils
Count: 0.5–1% of WBC
Size: 10–12 micrometers (the smallest granulocyte)
Nucleus: irregular in shape (irregular lobes or S-shaped) much less in-
tensively colored than neutrophils and eosinophils.
Cytoplasm: large blue granules stain metachromatically (like in mast
cells). They contain heparin and histamine.

– 77 –
 Function: They liberate heparin and histamine in response to an anti-
gen. They also defend against parasites. They are involved in most inflam-
matory reactions, including allergic reactions (like eosinophils).

Agranulocytes
Lymphocytes
Count: 20–45% of WBC
Size: They are smallest elements within WBC. Classification is very
difficult because their function does not always correspond with their mor-
phological differences. We divide them into two groups: small lympho-
cytes (6–8 µm) and large lymphocytes (8–18 µm). In the circulation the
small lymphocytes prevail (90%) – the large lymphocyte form is only 10%
of those in circulation.
Small lymphocyte – rounded cell nearly entirely occupied by the nu-
cleus (dense chromatin). The nucleolus can be demonstrated in electron
microscope only. Cytoplasm is reduced and forms a narrow rim around the
nucleus. It contains a few mitochondria, ribosomes, poor GER and Golgi
apparatus, one or two azurophilic granules (lysosomes).
Large lymphocyte – can be considered to be a lymphoblast. It is
a mother cell of the small lymphocytes and can also develop from the small
lymphocytes by dedifferentiation after antigenic stimulation. Such a lymph-

Fig. 67 Lymphoblast

– 78 –
oblast is able to differentiate into a specific immunocompetent lymphocyte
(i.e. immunocyte). These large lymphocytes occur mostly in lymph nodes
and lymph follicles.
Functional and developmental characteristic: Lymphocytes form
various subpopulations which play different roles in immune defense of the
organism. The lymphoblasts develop in the bone marrow from the multipo-
tent hemocytoblast (mesenchymal origin) and pass into the blood circula-
tion and mature in lymphoid tissue to be so-called immunocompetent cells.
This maturation process proceeds in two directions:

T-lymphocytes and cellular immune response

Lymphoblasts pass from bone marrow into thymus – the place where –
“Thymus dependent – i.e. T-lymphocytes” mature. They pass through
circulation into lymph nodes (paracortical region) – then pass again into
circulation and if they meet an antigen, they return to a lymph node and
dedifferentiate into a lymphoblast which undergoes mitosis and produc-
es a clone of activated lymphocytes (immunocytes). These lymphocytes
migrate in place of antigenic stimulation and form subpopulations which
can be identified by the presence of different surface markers (cluster of
differentiation, CD):
• T-helper lymphocytes (Th cells) – (surface marker CD4) secrete various
chemical messengers = interleukins, by which they help other lym-
phocytes to perform their functions (e.g. activation of Tc and B cells,
maturing monocytes into macrophages etc.)
• T-cytotoxic lymphocytes (Tc cell, surface marker CD8). They are acti-

vated by TH cells for killing virus infected cells and tumor cells
• T-regulatory lymphocytes (Treg cell) mostly suppress immune reactions

against self-antigens by switching off the immune response.
• T-memory lymphocytes (Tm cell) – remain in lymph node and can re-

spond to an antigen repeated in later life (immunological memory).

B-lymphocytes and humoral immune response

In addition to the thymus lymphocytes mature in birds in a special-
ized lymph organ, situated in the cloaca and called “bursa of Fabricius”
(Bursa-dependent = B-lymphocytes). In mammals the bursa-equivalent
has not been found and the B-lymphocytes undergo maturation directly in
bone-marrow. They are then activated in the lymph nodes, but in the corti-
cal region (follicles) and in spleen. Only few enter the circulation and upon

– 79 –
meeting an antigen they return and mature (after stimulation by TH cells)
in plasma cells which produce antibodies = immunoglobulins of various
classes (IgG, IgA, IgM, IgD, IgE). In addition to these plasma cells also
B-memory cells are produced.

Natural killer cells (NKC)

Next to the B- and T-lymphocytes, there exist also cells (non-specific)
without the properties of T and B cells. These are “natural killer cells”
(NKC) and they are not thymus or bursa dependent and mature in the bone
marrow and lymph organs. Their activity is stimulated and regulated by the
interleukins of T-helper cells. NKC play an important role in anti-tumor
activity (by production of a substance “perforin” which kills the tumor cells
perforating their plasma membrane).

Distribution of lymphocytes in the human body

Only 2% of all lymphocytes can be found in the blood circulation in the
relation: T-Ly=75%, B-Ly=15%, 0 (NKC)=10%. The majority of lympho-
cytes reside in the lymph nodes (40%), further the tissues (18%), spleen
(15%), thymus 10%), bone marrow (10%) and intestine (5%). Lifespan can
be very long (approx. 300 days).

Monocytes
Count: 2–10% of all WBC
Size: 12–20 µm (largest WBC)
Nucleus: large ovoid, kidney-shaped (horseshoe-shaped, sometimes
with deep indentations), chromatin not so dense as in lymphocytes, usually
two visible nucleoli
Cytoplasm: basophilic, few azurophilic granules (lysosomes), few
RER, polyribosomes
Monocytes are motile cells (pseudopodia) – in the blood circulation they
appear in their juvenile forms, when entering the tissues, they can differen-
tiate into macrophages. Their lifespan comprises about 3 days.

Thrombocytes
Count: 150 000–400 000 in mm3
Size: 2–4 µm
Thrombocytes (“blood platelets”) are ovoid, biconvex, non-nucleated
bodies. They are fragments of a giant megakaryocyte.

– 80 –
Fig. 68 Cooperation between cellular and humoral immune response
The T-lymphocytes recirculate between lymph nodes and tissue and may differentiate
into T-helpers (Th), T-cytotoxic (Tc), T-regulatory (Treg) or T-memory (Tm)
lymphocytes. The B-lymphocytes in the lymph nodes and lymphoid follicles
differentiate in plasma cells and B-memory (Bm) lymphocytes.

Fig. 69 Monocyte

– 81 –
Fig. 70 Thrombocyte

Their lifespan is about 4–12 days. The ground substance is light blue
stained – hyalomere – in its marginal part are the filaments and a system of
microtubules which open into invaginations of plasma membrane (through
which the platelet factors are released). The membrane is covered by a cell
coat (glycosaminoglycans which enable the platelet adhesion).
The central part is a dense blue granulomere (chromomere). It contains
in addition to some mitochondria various granules: Alpha-granules con-
tain platelet-specific proteins (e.g. platelet factor). Dense granules contain
calcium ions and serotonin. Lambda-granules contain lysosomal enzymes.
Function: Serotonin starts the contraction of the damaged vessel. The
platelet factor reacts with some plasma substances to form thromboplas-
tin. Thromboplastin reacts with prothrombin (a plasma protein) to form
thrombin. Thrombin reacts with fibrinogen (another plasma protein) giving
rise to a polymer fibrin, which then forms the thrombus (blood clot). The
thrombus as a result of blood coagulation contains also RBCs, WBCs, and
thrombocytes.

Hematopoiesis
The highly specialized blood cells with relatively short lifespans have to
be continuously replaced by new populations of cells, produced in hemo-
poietic tissues of mesenchymal origin. Blood cell development – hemato-
poiesis (or hemopoiesis) occurs in various stages during human ontogen-
esis:
1. Mesoblastic period: (1st–3rd embryonic month) Hematopoiesis starts
extraembryonically in the primary mesoderm (the source of mesen-
chyme) which is situated on the endodermal yolk sac wall, connecting
stalk and chorionic plate, and later in the first embryonic mesenchyme,
derived from the germ layers.

– 82 –
 The mesenchyme condenses into “blood islands”. Their mesenchymal
cells are called “angioblasts” and differentiate on the periphery into en-
dothelial cells and in the center into proerythroblasts and myeloblasts.

Fig. 71 Blood islands

2. Hepatolienal period: (2nd–8th fetal month) Starting from the second

month the mesenchymal part of the liver and from the fourth month also
the spleen serve as producers of most types of blood stem cells (pro-
erythroblasts, myeloblasts, megakaryoblasts - and from the 3rd month
also lymphoblasts).
3. Medullary period: Depends on ossification and consequently on the de-
velopment of the bone marrow. Even though the first ossification process
starts in the clavicle very early (end of 2nd month!), true hematopoiesis
begins in bone marrow approximately during the 5th month of develop-
ment and continues even into postnatal life, when the red bone marrow
represents the predominant hemopoietic tissue, from which all kinds
of blood cells develop in a process, named accordingly: erythropoie-
sis, leukopoiesis, lymphopoiesis, monopoiesis, and megakaryopoiesis
(thrombopoiesis).
According the monophyletic theory, all the blood elements develop from
a pluripotent hemopoietic stem cell – hemocytoblast. The process of dif-
ferentiation and maturation of all kinds of blood cells is shown in the pre-
sented diagram, from which is seen that e.g. during erythroblast maturation
the formation of hemoglobin starts and at the same time the degeneration
and extrusion of the nucleus occurs. During leukopoiesis the formation of
specific granules and segmentation of nucleus etc. occur.

– 83 –
Fig. 72 Hematopoiesis

Parameter Reference limits Units

Peripheral blood smear    
Red blood cell (RBC) count (in male) 4.0 mil.–5.8 mil. /mm3
Red blood cell count (in female) 3.8 mil.–5.2 mil. /mm3
Hemoglobin (in male) 130–160 g/l
Hemoglobin (in female) 120–160 g/l
Hematocrit (HCT) (in male) 0.40–0.50 –
Hematocrit (in female) 0.35–0.47 –
Mean corpuscular volume (MCV) = HCT/RBC 82–98 fl
Red blood cell distribution width (RDW, variability
of RBC size) 10–15.2 %
Mean corpuscular hemoglobin (MCH) 28–34 pg
Mean corpuscular hemoglobin concentration (MCHC) 320–360 g/l
Reticulocyte count 0.5–2.5 % –

– 84 –
 White blood cells (WBC, leukocytes) 4000–10000 /mm3
Platelets (thrombocytes) 150000–400000 /mm3

White blood cell differential count    

Lymphocytes 20–45% –
Monocytes 2–10% –
Segmented neutrophilic granulocytes
(PMN, polymorphonuclears) 45–70% –
Nonsegmented neutrophilic granulocytes (bands, stabs) 0–4% –
Eosinophilic granulocytes 0–5% –
Basophilic granulocytes 0–2% –

C. Muscle tissue

Origin: mesenchyme
Function: generating force by contraction, i.e. shortening and thicken-
ing of cells (fibers); creating (in some cells only) and propagating (spread-
ing) electric action potentials
Morphology: there are two main types: smooth and striated muscle.
In smooth muscle, the intracellular contractile proteins are not organized
in a periodic manner. In striated muscle, the contractile proteins are ar-
ranged in repeating units named sarcomeres and the cells and fibers exhib-
it cross-striations at the light microscope level. The striated (sarcomeric)
muscle tissue occurs in two forms with different microscopic and physio-
logic properties: skeletal muscle and cardiac muscle.

Smooth muscle

Distribution: The uterus comprises the biggest accumulation, the mus-

cle layers of the wall of the digestive tube (from the middle part of the
esophagus to the anus), the muscle layers of the bronchi and bronchioles,
arteries, veins, large lymphatics, arrector pili muscle, areola of the mamma-
ry gland, scrotum, iris (ectomesenchymal origin!), ductus deferens. Smooth
muscle cells are independent of direct voluntary control, though the rate
and strength of contractions are modulated by the autonomic nervous sys-
tem as they are innervated by autonomic nerve system.

– 85 –
Fig. 73 Bundle of smooth muscle cells connected with gap junctions

Morphology: Smooth muscle consists of 20–400 µm long spindle

shaped cells. These cells are non-striated and may be packed in bundles
by a network of reticular fibers. The cells are invested by a thick extracel-
lular coating (basal lamina) which together with the gap junctions enable
coordinated contraction (e.g. peristalsis in the intestine). Among the cells
and around their bundles also a little connective tissue with collagen fibers,
blood vessels and nerves can occur.
The plasmalemma which (together with the surrounding basal lamina)
in muscle is called sarcolemma contains many small inpocketings, called
caveoli (pinocytic vesicles important for Ca intake). These cavities increase
the cell surface and have the same function as the T-tubules of striated
muscles (see below). The caveoli are often continuous with microtubules.
The cytoplasm, i.e. sarcoplasm, contains only one elongated, rod shaped
and centrally situated nucleus. Next to it there appear some long slender
mitochondria, a small Golgi complex, few cisterns of granular endoplas-
mic reticulum and clusters of free ribosomes. The contractile elements are
present in the form of actin and myosin filaments, forming a fine network.
These proteins are inserted into focal densities. These sarcolemma and sar-
coplasma dense bodies represent an equivalent of the Z disc of striated
muscle. With contraction the cells change their shape. The thin filaments
are of actin and tropomyosin (troponin of striated muscle is absent) and
they interact with thicker myosin filaments by a sliding mechanism (similar
to that in striated muscles). This mechanism is based on phosphorylation of

– 86 –
Fig. 74 Smooth muscle cell

myosin. The Ca ions must react with a calcium binding protein – calmod-
ulin – to activate myosin kinase, responsible for myosin phosphorylation.
The phosphorylated myosin is able to interact with actin, thus generating
the contraction force.

Fig. 75 Myocyte contraction

Striated (sarcomeric) muscle

can be divided into skeletal and cardiac muscle.

Skeletal muscle
Skeletal muscle is under voluntary control and is attached to the skel-
eton or to the skin (facial muscles). It is composed of long, cylindrical
and multinucleated syncytial fibers, grouped in fascicles. The fibers can be

– 87 –
from 10 µm to 400 mm in length. The whole muscle is enclosed by a dense
connective tissue sheath named epimysium, from which collagenous sep-
ta surround the fascicles, thus forming an envelope named perimysium.
A delicate layer of reticular connective tissue named endomysium passes
among the individual muscle fibers. In these connective tissue septa pass
the blood vessels (rich capillary network) and nerves.
Each muscle fiber is enclosed by a  delicate membrane  – sarcolem-
ma – (which includes also an extracellular glycoprotein coating and basal
lamina). The sarcoplasm (cytoplasmic matrix) contains numerous nuclei
(sometimes several hundred!) and a large number of myofibrils, arranged
in groups in Cohnheim’s fields (these are seen in cross section after his-
tological processing, separated by various amount of myoglobin). Each
muscle fiber contains a number of nuclei, which are positioned under the

Fig. 76 Skeletal muscle fascicles

Fig. 77 Myofibrils grouped in Cohnheim’s fields, peripheral position of nucleus

– 88 –
sarcolemma. Near each nucleus is a small Golgi apparatus and there are
many mitochondria mostly under the sarcolemma.
The myofibrils run in parallel longitudinally and are cross-striated. The
dark staining bands are doubly refractile or optically anisotropic A-bands,
the light bands are optically isotropic – I-bands. Each I-band is halved by
a transverse line Z-line. Each A-band is crossed by a M-line. The structural
and functional unit between two successive Z-lines is called sarcomere and
is approx. 2.5 µm long.
Ultrastructure: A myofibril represents a bundle of 2 types of filaments –
thin and thick – running symmetrically and parallel to the fibrillar axis. The
Z-line has the form of a zigzag line in which the thin filaments are an-
chored. These thin, i.e. actin filaments form the I-band and are about 1 µm
long and 8 nm wide. The thin filaments are composed of 3 proteins: actin,
tropomyosin, and troponin. The main component is actin – a twisted dou-
ble filamentous polymer which carries thin and short filamentous molecules
of tropomyosin on which three small troponin subunits are attached.

Fig. 78 Skeletal muscle fiber

– 89 –
Fig. 79 Thin myofilament composed of actin and associated proteins

Fig. 80 Sarcomere

The thick, i.e. myosin filaments form the A-band, are 1.6 µm long and
15 nm wide and are arranged in parallel among thin filaments in form of
a comb. Each rod consists of hundreds of myosin molecules. The heads of
these molecules appear as tiny outgrowths. The thick filaments are inter-
connected in the middle by M-line (contains creatine kinase, important for
supply of ATP). During muscle contraction the actin filaments slide in be-
tween the myosin filaments and so the whole sarcomere shortens. The ends
of thin filaments reach nearer to the opposite ones and form between them
a lighter zone, the H-band which becomes very narrow in full contraction
and widens during relaxation of the muscle fiber.
The intake of Ca ions occurs through the transverse tubule system, con-
sisting of a tubular invagination of the sarcolemma named T-tubule which
encircles the myofibrils at the level of the A-I junction.
Adjacent to both sides of each T-tubule are situated the terminal (trans-
verse) cisternae of the sarcoplasmic reticulum and they form together with

– 90 –
Fig. 81 Contraction of a sarcomere in striated muscle

the T-tubule a triad. The T-tubule is not a part of sarcoplasmic reticulum.

The terminal cisternae continue in a branching system of the longitudinal
sarcotubules of sarcoplasmic reticulum, which contains the Ca ions. Cal-
cium is released into myofibrils, binds to troponin, which exposes myo-
sin-binding sites on actin, allowing cross bridges between actin and myosin
to form.

Fig. 82 Ultrastructure of a skeletal muscle fiber

Mechanism of contraction
In normal unstimulated conditions the troponin and tropomyosin mole-
cules prevent the actin molecu­les from interacting with myosin. Both reg-
ulatory proteins lose their protective function in presence of Ca ions and
actin and myosin interact with each other. (The Ca ions bind to the troponin,
the tropomyosin molecule is pushed deeper in action helix and the binding
site of actin is exposed to myosin). The myosin heads contain an ATPase.

– 91 –
Fig. 83 Interaction between actin and myosin filaments

During the relaxed state, the ATPase hydrolyzes ATP to ADP and inorganic
phosphate (Pi). Once myosin is bound to actin, the Pi molecule is released
and the power stroke occurs, pulling actin relative to myosin. ADP then is
released and a new ATP molecule can bind. The cycle continues as long as
Ca++ is available

Myosatellite cells
Multinucleated skeletal muscle fibers cannot divide but can grow larger
in response to muscle activity due to lengthening and increasing their my-
ofibrils, i.e. not to addition of new muscle fibers. But in case of e.g. injury
they can be replaced by new muscle fibers, which differentiate from satel-
lite (myosatellite) cells. These are unipotential stem cells, closely attached
to the surface of the muscle fiber, and covered by the same basal lamina.
They are mitotically quiet in the adult, but in case of necessity they pro-
liferate and become a source of new myoblasts (muscle cell precursors),
which undergo cell divisions before they can fuse with existing myofibers.
However in case of massively damaged muscle fibers the muscle becomes
replaced by a fibrous tissue.

Fig. 84 Myosatellite cell

– 92 –
Cardiac muscle
forms the middle layer of the heart wall, i.e. the myocardium. Some
cardiac muscle cells are also present in the walls of the pulmonary vein
and superior vena cava. Even though it is striated, it differs from skeletal
muscle by its involuntary activity and by some additional morphological
features. In contrast to skeletal muscle it is not formed by long multinu-
cleated fibers, but by single cardiac muscle cells which are joined end to
end by cell junction to form fibers. These cardiac muscle fibers branch and
anastomose, forming a special sort of syncytium, which enables spreading
of a contraction wave. The endomysium among the muscle fibers is a very
vascular loose connective tissue, containing many blood capillaries and
lymphatic vessels.
The cells are about 15 µm in diameter and 80–150 µm in length and pos-
sess one or two centrally located pale nuclei. There are pigment granules
(lipofuscin) near the poles of a nucleus, as well as a small Golgi complex.
The abundant mitochondria are situated mostly in rows among the myofi-
brils. These myofibrils are striated but they are not arranged in Cohnheim’s
fields, are more delicate and spread throughout the whole fiber.
The border between two adjacent cells is formed by the intercalated
discs. It is a darkly stained transverse line across the fiber which repre-
sents a junctional complex. It is usually steplike arranged. In the transverse
portion (fascia adherens) the actin filaments are anchored in the form of
desmosomes (macula adherens). The lateral portion of the disc contains
a gap junction (nexus) which allows the ions to pass through the junction.

Fig. 85 Cardiac muscle

– 93 –
Fig. 86 Intercalated disc

The sarcolemma is penetrated by T-tubules at the level of the Z-line, the

sarcoplasmic reticulum is not so well developed, and transversal cisterns
are missing – we speak, instead of triads, about dyads (1 tubule + 1 cistern).

Cardiac conducting system

In addition to the cardiac muscle cells whose function is contraction,
there exists a specialized system for initiating impulses (“pacemaker”), and
to conduct them through the heart. This system consists of the sinoatrial

Fig. 87 Cardiac conducting system

– 94 –
Fig. 88 Purkinje fibers

node, the atrioventricular node, situated beneath the endocardium (see

location on the diagram) and atrioventricular bundle (bundle of His).
The cells of the cardiac conducting system retain the ability of embryonic
cardiac muscle cells to generate action potentials spontaneously. Although
all cardiac muscle cells generate action potentials, the firing rate of the
sinoatrial controls the heart rate under normal conditions.
The bundle of His enters the fibrous portion of the interventricular sep-
tum from the A-V node and divides into two branches, distributed to right
and left ventricles.
The structure of the nodes is represented by specialized cells, smaller
than ordinary cardiac muscle cells, arranged in a network embedded in
dense connective tissue. The cells of the atrioventricular bundle conduct the
wave of depolarization and are formed by specialized conducting muscle
fibers, called Purkinje (Purkyně’s) fibers (Jan Ev. Purkyně was a famous
Czech scientist, 1787–1869). Purkinje fibers are situated deep in the en-
docardium and are much larger then cardiomyocytes and have one or two
nuclei in a clear central mass of sarcoplasm (which contains much glyco-
gen), which possess many mitochondria and only few striated myofibrils,
arranged peripherally. The intercalated discs are not typical, but there are
also desmosomes along the cell boundaries between adjacent fibers.

Specialized myocardiocytes – myoendocrine cells

Among the cardiac muscle cells of the right atrium appear specialized
cardiac myocytes – myoendocrine cells. They possess many osmiophilic
(i.e., staining with osmium salts) granules mostly in the perinuclear Golgi
region, but also in rows between myofibrils. Their function is endocrine,
they produce the hormone atrial natriuretic peptide (cardiodilatin – regu-
lation of blood pressure). They are rarely found also in the interventricular
septum.

– 95 –
Fig. 89 Myoendocrine cell in atrial myocardium

D. Nerve tissue

Origin: ectoderm
Function: reception of stimuli from environment, formation and con-
duction of nerve impulses, storage and processing of information, coordi-
nation of other body functions, secretion of neurohormones.
Morphology: Nerve tissue contains two major groups of cells: the neu-
rons and the neuroglia.

Neurons

The morphological and functional unit of nerve tissue is a neuron. The

neuron consists of a cell body, (also called perikaryon, or soma) and pro-
cesses.
The processes are of two kinds:
1. Dendrites, which form the receptor portion of the neuron, and are spe-
cialized in receiving stimuli from the environment (or other neurons)
and conducting them toward the cell body (afferent conduction), and
2. Axon (or neurite) which is always single and conducts impulses away
from the cell body (efferent conduction). The distal (i.e. effector) portion
of an axon is branched into terminal arborizations, ending by axon ter-
minals (knob-like dilatations, fr. boutons terminaux) which form the syn-
apses, in which an impulse is transmitted to the next neuron or effector.

– 96 –
Fig. 90 Neuron

Classification of neurons
The central nervous system contains about 100 billion neurons. They
can be classified according to the number of their processes. Whereas there
is always only a single axon, the dendrites can vary in the number:

1. The embryonic neuroblasts represent a cell without processes and can be

considered as apolar neurons.
2. During early development the first process gradually appears – it is an
axon. To such unipolar neurons also olfactory axons can be with some
reservation added (unmyelinated axons of the olfactory cells with no
typical dendrites).

– 97 –
3. Neurons which possess a single axon and single dendrite are bipolar
neurons. They appear as intermediate neurons, e.g. in the retina of the
eye, but also in the ganglia of the vestibulocochlear nerve (VIII.), as well
as in the cerebrospinal ganglia of lower vertebrates (fishes).
4. From the bipolar neurons the pseudounipolar neurons developed by
gradual fusing of the dendrite and axon. They are situated in spinal gan-
glia of higher vertebrates (including human). This sensory neuron pos-
sesses only single process, which then divides into two branches. They
can be functionally considered as dendrite and axon (both are myelinat-
ed) and the stimuli do not pass through the cell body, which has a trophic
function only.
5. Most neurons possess more than one dendrite – these are multipolar
neurons. Typical star-shaped neurons belong mostly to motor neu-
rons (e.g. situated in anterior horns of spinal cord), possess numerous
branched dendrites capable of receiving stimuli from many other neu-

Fig. 91 Types of neurons

– 98 –
 rons, and a single axon, conducting the stimulus to the effector (muscle,
glands). They can be also pyramid-shaped (motor brain cortex), or pear
shaped (Purkinje) cells of cerebellum).

Cytology of the neuron

The cell body (also called perikaryon, or soma) is large, usually star-
shaped, containing a centrally located large, pale and vesicular nucleus
with a conspicuous deeply staining nucleolus (similar to that of an oocyte).
There is no centrosome – that is why once a nerve cell has been differen-
tiated, it loses the ability to divide. Golgi complex is located in the form of
cisterns around the nucleus like a wreath. (This apparatus was discovered
by Camillo Golgi just in the nerve cell body in 1898). Numerous mitochon-
dria witness the heavy energy demands of the neuron.

Fig. 92 Cell body of a neuron

– 99 –
 Nissl bodies in the form of large basophilic granular areas consist of
rough endoplasmic reticulum and polyribosomes and are sites of active
protein synthesis. In exhausted neurons there is a temporary reduction of
Nissl bodies (tigrolysis or chromatolysis). Nissl bodies also extend into
dendrites but are absent from the axon hillock.
The neurofibrils are composed of neurofilaments (diameter 10 nm) and
neurotubules (microtubules – 24 nm), which also extend into all processes.
The granules of a brown, age dependent pigment, called lipofuscin are
found in the axon hillock. In some CNS ganglia black pigment granules of
neuromelanin can also be observed.
Dendrites are afferent processes sometimes with rich branching which
enlarges the area of reception of nerve impulses. Arborization and dendritic
spines enable contacts with terminal arborizations of other neurons (there
can be thousands of synapses). The larger dendrites contain most of the
same organelles as the cell body.
The axon is usually the largest and the longest process of the neuron,
reaching up to 100 cm in length (e.g., in motor neurons innervating the
foot muscles) with a constant diameter along its course. It is covered by
axolemma and it can branch in axon collaterals and at the end it ramifies
into terminal arborizations.
Axoplasm contains no Nissl bodies or ribosomes (proteins are supplied
from the cell body). It contains neurofilaments and neurotubules which
are protein tubular fibers running parallel to longitudinal axis of the axon.
There are also microfilaments built of the protein actin – these can run
crosswise to be fixed to the axolemma. In addition to the filaments the
mitochondria, neurotransmitter vesicles and lysosomes, as well as ax-
oplasmic reticulum cisterns (of unknown function) can also be observed.

Fig. 93 Axon sheaths

– 100 –
Fig. 94 Development of myelin sheath

The axon leaves the cell body at an axon hillock from which the bundles
of neurofilaments and neurotubules continue into the initial segment. It is
the naked part of the axon in which the action potential starts.
After the axon hillock the axon of myelinated fibers becomes invested
by a segmented myelin sheath, interrupted at regular intervals by mye-
lin-free gaps – nodes of Ranvier. The part between two sequential nodes is
called an internodal segment and is covered by one oligodendrocyte glia
cell (in CNS) or Schwann glia cell (in PNS), which is responsible for pro-
duction of myelin. During development of a PNS neuron the Schwann cell
wraps round the axon and rotates around it and gradually forms thinner and
thinner layers of pulled over cell membrane of the Schwann cell. The re-
sulting myelin sheath consists therefore of mainly lipoprotein turns (from
few to 50) of plasmalemma and a little cytoplasm, which projects near the
node (paranodal zone) in little tongues (loops), bent up to contact the axon.

Fig. 95 Node of Ranvier

– 101 –
 Near the paranodal zone the myelin incisures (clefts) can be seen. These
cone-shaped figures are the result of dehiscence and loss of the plasma-
lemma layers in oblique convergent lines during myelination.

Unmyelinated fibers
In addition to the myelinated fibers, many fibers of peripheral and central
nervous system as well as most of those in autonomic nervous system are
unmyelinated (grey or Remak fibers). In those nerves as many as nine ax-
ons may be enfolded by each Schwann cell. The myelin sheath is absent and
therefore also Ranvier’s nodes are not present (i.e. non-segmented fibers).

Fig. 96 Grey fibers in PNS (one Schwann cell encloses multiple fibers)

Myelinated fibers of CNS

In the white matter of the CNS the fibers (axons) are also enclosed with-
in the myelin sheath but instead of Schwann cells, there are oligodendro-
cytes which are responsible for production of myelin. The difference be-
tween them is that whereas Schwann cells build the myelin on one single
axon only, the oligodendrocyte sends more processes which wrap several
axons to build the myelin of white matter. Even though the Ranvier’s nodes
occur, the myelin clefts in the CNS myelinated fibers are absent.

Peripheral nerve

The nerve is formed by fibers, running in bundles, covered by a connec-

tive tissue coat. The myelin-ensheathed axons with Schwann cells are en-
veloped by a thin layer of connective tissue forming endoneurium. A bun-
dle of axons is covered by flat cells of perineurium and the whole nerve is
enveloped by a fibrous coat of dense connective tissue – the epineurium.

– 102 –
Fig. 97 Oligodendrocyte providing a glial sheath and a myelin sheath in CNS

Fig. 98 Peripheral nerve

Synapses and a reflex arc

The contact among neurons or between a neuron and effector tissue

(muscle, gland etc.) is realized through a special arrangement – the synapse.
The interneuronal contact can occur in various sites of the neuron. The most
common is the axo-dendritic synapse, i.e. the synapse of end-branches of
terminal arborizations with the dendrites of the next neuron.
Another type is the axo-somatic synapse. In this case the axon contacts
the cell body (soma) of another neuron directly. An axon can form a syn-

– 103 –
Fig. 99 Synapses

apse only at an unmyelinated site. The dendrites or cell body of one neuron
can be contacted by few axonal branches, but some of them (e.g. pyramidal
cells) by many – and form as many as 10 000 synapses.
Nerve fibers can carry the information from a receptor inside or outside
of the body to the center (centripetally) – such fibers are afferent i.e. senso-

Fig. 100 Reflex arc

– 104 –
ry. From the CNS the impulses are carried by efferent i.e. motor fibers to
the effector organs. Simple contacts of both kinds of these nerve fibers are
represented by the so called reflex arc. The afferent sensory neuron starts
in this case on the periphery in the skin by its free endings of dendrites and
passes through spinal ganglion (cell body of the pseudounipolar cells), from
which its axon continues into dorsal root of the spinal cord gray matter. In
the ventral horns the stimulus is transmitted (an axo-dendritic synapse) to
the dendrites of an efferent multipolar neuron and passes via its axon to the
effector organ (usually muscle).

Sensory receptors

The peripheral end of the afferent neuron, where the sensory pathway
starts, serves as a receptor, which can respond to various stimuli from the
external environment or internal situation of the body and its parts. Detec-
tion of cutaneous sensation occurs by variably specialized nerve endings,
the most important of which are:

Free nerve endings

These are formed by nonmyelinated fibers (dendrites) branched in the
deep layers of epidermis. They detect pain and temperature (nociceptors
and thermoreceptors). On the palms and soles the free endings can be at-
tached to special basal epidermal cells with a lobulated nucleus and nu-
merous granules, known as Merkel cells (mechanoreceptors – sensation
of touch).

Fig. 101 Free nerve endings and Merkel cell

– 105 –
Meissner’s corpuscles
These are encapsulated nerve endings confined to the dermal papillae.
Their capsule consists of fibroblasts and collagen fibers surrounding an
inner core of spirally arranged Schwann cells and nerve terminals. They
are situated vertically in the dermal papillae and are most numerous on the
feet and hands. They are considered as the most sensitive mechanoreceptors
detecting touch.

Fig. 102 Meissner’s corpuscle in the dermal papilla below the epidermis

Pacinian corpuscles
These are large mechanoreceptors (up to 1 mm) situated mostly in the
deep dermis of the digits or subcutaneous fat, as well as in the periosteum,
mesenteries etc. where they detect pressure and vibration. Their capsule
consists of many concentrically arranged lamellae which are modified
Schwann cells separated from each other by fluid filled spaces. The lamel-
lae surround centrally situated unmyelinated nerve terminals.

Muscle spindles
These form special sense organs situated between the muscle fibers in
perimysium. They are about 1.5 mm long and consist of a connective tissue

– 106 –
Fig. 103 Pacinian corpuscle

Fig. 104 Muscle spindle

capsule, surrounding some specialized myofibers (intrafusal fibers). These

fibers lose their cross-striation in their equatorial region in which many
nuclei accumulate. Sensory nerve fibers penetrate the capsule and their un-
myelinated dendrites encircle the intrafusal fibers and register stretch and
tension. Each of the intrafusal fibers also receives a motor innervation in
the form of motor end plates.
Similar structures are found in tendons near the insertion of muscle fib-
ers – Golgi tendon organs. In these organs the connective tissue sheath
encapsulates bundles of collagen fibers, surrounded by sensory nerve end-
ings which respond to stretch.

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Motor nerve endings
The efferent motor neurons usually terminate in a small branched struc-
ture – a motor end plate. The terminal axon loses its myelin, covered only
by the Schwann cell forms a close irregular contact with the muscle fiber.
It is irregular because the sarcolemma is folded in clefts and ridges, called
junctional folds, in the places of contact. Between the axolemma and sarco-
lemma is a narrow intercellular gap – the synaptic cleft. The axon terminals
contain numerous synaptic vesicles with the neurotransmitter acetylcho-
line. The signal is transmitted from axon to muscle by this neurotransmitter
which initiates a wave of depolarization of the muscle fiber. Meanwhile the
acetylcholine is hydrolyzed by the enzyme cholinesterase present in the
synaptic cleft.

Fig. 105 Motor end plate

Conduction of nerve impulses

The conduction of a nerve impulse depends on the content of sodium-

and potassium ions in the fluid inside and outside the neuron. The sodi-
um-ion is a sodium atom, which has one negative electron given away so
that it carries a positive electric charge. There is a ten times higher concen-
tration of sodium-ions in extracellular fluid than inside the neuron. On the
other hand the potassium concentration is 20–40 times higher inside than
outside the neuron. The axolemma is only slightly permeable to both types

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Fig. 106 The Na+/K+ ATPase and ion channels in a membrane of a neuron

of ions, but significantly more to potassium, – so that the sodium-ions dif-

fuse slowly into neuron and on the contrary the potassium-ions leave the
neuron at a somewhat faster rate.
The concentration balance must be maintained by special sodium-po-
tassium-pumps (protein molecules), which continuously pump out sodium
as they pump in potassium. This provides the concentration gradients that
drive diffusion of these ions both at rest (mainly potassium, diffusion of
which creates the resting membrane potential of approximately -70mV)
and during the action potential (mainly driven by sodium diffusion, as de-
scribed below).
Excitation causes opening of channels of voltage-regulated integral pro-
teins, the sodium enters into the cell and the axon becomes depolarized –
action potential. Later, on the contrary, the potassium ions leave the axon
and the resting potential becomes again restored. In myelinated fibers de-
polarization occurs in Ranvier’s nodes only – in this case the nerve impulse
has to jump from one node to the next one – saltatory conduction – and
the action potential is conducted approximately 100× faster than in nonmy-
elinated fibers.

Fig. 107 Saltatory conduction of action potential between two Ranvier nodes of
a myelinated fiber

– 109 –
 Nerve signals are of electric nature while they are spread lengthways
along the nerve fiber. At the moment they reach the end of it, they must
jump over the synaptic cleft in a chemical way, i.e. with the help of a trans-
mitter substance.
Circulation of a neurotransmitter starts in the vicinity of the nucleus
and it travels in a rapid transport to the end of the nerve fiber. As soon as the
nerve excitation reaches the synapse, the calcium channels open and calci-
um enters the presynaptic bulb and helps to fuse the vesicles among them-
selves and with the presynaptic axolemma. The transport vesicles join the
axolemma and evacuate their content (exocytosis). The neurotransmitter
molecules traverse the synaptic cleft and join the receptors of the postsyn-
aptic membrane and transmit the nerve excitation, i.e. causes the increased
permeability of the postsynaptic membrane to ions, usually sodium, and its
depolarization and generation of active potential in the next neuron. The
neurotransmitter is either enzymatically degraded in the synaptic cleft (e.g.,
acetylcholine is degraded by cholinesterase) or taken back up into the pre-
synaptic cell to be used again. After endocytosis, the vesicles containing the
synaptic cleft fluid with remaining transmitter molecules become shifted
back into the cell body where they are split by lysosomes and their content
can contribute to the formation of new vesicles.
The presynaptic terminals resemble an endocrine gland, and the chemi-
cal transmission is a modified form of hormone secretion. There are varie-

Fig. 108 Synapse

– 110 –
ties of small molecules (e.g. acetylcholine, norepinephrine, glycine, seroto-
nin, dopamine etc.) which can serve as transmitters and so can also various
peptides.

Fig. 109 Neurotransmitter circulation

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Neuroglia

In addition to the nervous elements proper, the nervous system contains

numerous non-neural support cells – so called neuroglia cells. These are
situated either in CNS, like macroglia (astrocytes and oligodendrocytes)
and microglia and ependymal cells, as well as in peripheral NS like the
already mentioned Schwann cells and satellite cells. These cells are also of
ectodermal origin (except mesenchymal microglia) and develop from the
spongioblasts or the lining of the primitive neural tube. In early ontogeny
they guide the migration of developing nerve cells.

Astrocytes
The astrocytes provide structural support for nerve tissue. These star-
shaped cells are the largest of the glial cells. They possess oval, pale nuclei
and long cytoplasmic processes (named pedicles) with expanded tips that
adhere to the vessels. These perivascular feet can induce changes in the
endothelium so that it acts as a barrier to diffusion between blood and brain.
Astrocytes also regulate the potassium level, altered by neuronal activity
and transport it to the brain surface and cerebrospinal fluid. Other processes
form a layer under the pia mater and separate it from the nerve cells. As-
trocytes, unlike neurons, can undergo mitosis and participate in repair of
injured CNS by their proliferation and formation of a glia scar.

Fig. 110 Astrocytes

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Fig. 111 Oligodendrocyte and microglia

There are two subtypes of astrocytes:

Fibrous astrocytes are most evident in the white matter and have few
long, not very branched processes, which contain rich bundles of cytoskel-
etal intermediate filaments (glial fibrillary acidic protein).
Protoplasmic astrocytes are present in gray matter and possess many
branched and relatively short processes.

Oligodendrocytes
They are smaller with few slender processes, situated in rows along
nerve fibers. They are the myelin-forming cells of the CNS and are analo-
gous to the Schwann cells which form the myelin of peripheral nerves. In
contrast to a Schwann cell which produces the myelin by rotation around
one axon only, one oligodendrocyte wraps its processes spirally around
several neurons (see the diagram on preceding pages).

Microglia cells
They do not belong in fact to the glial elements because of their mes-
enchymal origin. That is why they are sometimes called mesoglia. Func-
tionally they can be considered as specialized immune cells in the CNS, as
specialized macrophages. They are tiny cells with rod-shaped nuclei and
comparatively long ramifying spiny processes. They form about 10% of

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the neuroglia and increase in size in damaged CNS and become actively
motile and phagocytic.

Ependymal cells
They are epithelially arranged in a layer called ependyma, which lines
the cavities of the brain (ventricles) and the central canal of the spinal cord.
Ependyma consists of two cell types:
Ependymal cells are cuboidal cells linked by desmosomes with apical
microvilli and cilia and abundant mitochondria, a small oval basal nucleus,
Golgi complex and GER. The basal part does not lie on basement mem-
brane and is in contact with astrocytic processes.
Specialized ependymal cells – tanycytes – are found in the floor of the
3 ventricle. The basal process of tanycytes extends and forms end feet on
a blood vessel. They are attached to each other and to the ependymal cells
by tight junctions. Modified ependymal cells cover, as cuboid to columnar
epithelium-like lining, the choroid plexus, which represents folds of pia
mater. They secrete cerebrospinal fluid (daily 600–700 ml).

Fig. 112 Ependyma

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Fig. 113 Satellite cells surrounding a pseudounipolar neuron in a spinal ganglion

Satellite cells
They are support cells which surround the cell bodies of craniospinal
as well as autonomic ganglia. They are small cuboidal cells, resembling
Schwann cells and forming a layer around the craniospinal ganglia and an
incomplete layer around the autonomic and intramural ganglia.

Meninges

The central nervous system is wrapped up in three protective coats – the

meninges:

Pia mater
The innermost layer of meninges, covered by squamous cells of mesen-
chymal origin. The delicate membrane composed of loose connective tissue
also accompanies the vessels and lines their perivascular space up to their
transition in the capillaries. The pia does not adhere to the surface of nerve
tissue because of close contact with processes of astrocytes.

Arachnoid
Middle layer of meninges separated from the dura mater by a thin sub-
dural space. It is connective tissue, containing collagen fibers and covered
by a layer of cells as in the pia mater. Under the roof is an irregular system
of trabeculae – the subarachnoid space, filled with cerebrospinal fluid.
In some places the arachnoid projects into the dural sinuses in form of

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Fig. 114 Meninges

arachnoid villi. There the cerebrospinal fluid is resorbed into the blood of
the venous sinuses.

Dura mater
The outermost layer is made of dense connective tissue, continuous with
the periosteum. It contains collagen fibers with some elastic fibers. The in-
ternal surface of dura is covered by simple squamous epithelium of mesen-
chymal origin. This kind of epithelium also covers the dura in spinal cord.

Blood-brain barrier

The CNS is protected from toxic and other dangerous compounds that
may get into the blood stream by a functional barrier, which results from
the reduced permeability of the blood capillaries of nerve tissue. The lin-
ing endothelial cells are not fenestrated and are joined by continuous tight
junctions. The capillaries are in addition surrounded by a thick basal lamina
and covered by processes of astrocytes.

Cerebrospinal fluid

Cerebrospinal fluid is considered as “cushioning fluid” of CNS and fills

the brain vesicles, spinal central canal and the subarachnoid space. It repre-

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sents a modified tissue fluid which can contain a few leukocytes. It is pro-
duced by choroid plexuses of brain vesicles (derived from ependyma) and
passes through openings in the roof of the hindbrain to the subarachnoid
space, and becomes resorbed into the blood from arachnoid villi. The CSF
also drains the tissue fluid of the brain.

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FIGURE CAPTIONS

Fig.   1 Shapes of cells 8

Fig.   2 The cell 9
Fig.   3 Cell membrane 10
Fig.   4 Cellular processing of external signals 11
Fig.   5 Membrane transport 12
Fig.   6 Exocytosis and endocytosis 13
Fig.   7 Transcytosis 13
Fig.   8 Nucleus 14
Fig.   9 Molecule of DNA 16
Fig. 10 Chromatin fiber 17
Fig. 11 Condensed chromosome visible and stained during mitosis 17
Fig. 12 Human male karyotype 18
Fig. 13 Barr body in a neutrophilic granulocyte of a female 19
Fig. 14 DNA replication and doubling of chromatids 19
Fig. 15 Cell cycle and average duration of its phases 20
Fig. 16 Chromosomes during mitotic cell division 21
Fig. 17 From genetic information to the protein 22
Fig. 18 Ribosome 23
Fig. 19 Rough endoplasmic reticulum (RER) 25
Fig. 20 Mitochondrion 27
Fig. 21 Centrosome and centriole 30
Fig. 22 Actin filament as a part of the contractile apparatus 31
Fig. 23 Microvilli 34
Fig. 24 Stereocilia and kinocilia 35
Fig. 25 Basement membrane 36
Fig. 26 Junctional complex 37
Fig. 27 Simple epithelia 38
Fig. 28 Stratified squamous epithelia 39
Fig. 29 Stratified columnar epithelium 39
Fig. 30 Transitional epithelium (urothelium) in contracted and relaxed shape 40
Fig. 31 Types of exocrine glands according to shape 41

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Fig. 32 Patterns of secretion 42
Fig. 33 Serous and mucous cells 43
Fig. 34 Seromucous gland in a section (left) and surface view (right) 44
Fig. 35 Fibroblast and fibrocyte 45
Fig. 36 Reticular cell 46
Fig. 37 Adipocytes 46
Fig. 38 Melanocyte and mastocyte 47
Fig. 39 Macrophage and plasmocyte 48
Fig. 40 Assembly of a collagen microfibril, a fiber and a bundle of fibers 50
Fig. 41 Reticular fibers and elastic fibers 51
Fig. 42 Mesenchyme and loose connective tissue 53
Fig. 43 Regular dense collagenous (left) and elastic (right) connective tissue 53
Fig. 44 Hyaline cartilage and chondrocyte 55
Fig. 45 Fibrous cartilage 56
Fig. 46 Osteocytes 57
Fig. 47 Long and flat bone 57
Fig. 48 Spongy bone 58
Fig. 49 Compact bone 59
Fig. 50 Osteon 59
Fig. 51 Section of compact bone showing the lamellas of an osteon 60
Fig. 52 Intramembranous ossification 61
Fig. 53 Primary bone trabeculae 61
Fig. 54 Principles of endochondral ossification 63
Fig. 55 Zones of endochondral ossification (upper scheme) and cross section
showing the penetration of blood vessels into an ossification center
(lower scheme) 64
Fig. 56 Primordia of two dentitions 65
Fig. 57 Early stages of tooth development 66
Fig. 58 Bell stage of tooth development 67
Fig. 59 Enamel organ 67
Fig. 60 The tooth 69
Fig. 61 Formation and structure of the enamel 70
Fig. 62 Odontoblasts 71
Fig. 63 Dentin 71
Fig. 64 Erythrocyte 74
Fig. 65 Neutrophilic, eosinophilic, and basophilic granulocytes 75
Fig. 66 Eosinophilic granule (0.3–1.0 µm) 77
Fig. 67 Lymphoblast 78
Fig. 68 Cooperation between cellular and humoral immune response
The T-lymphocytes recirculate between lymph nodes and tissue
and may differentiate into T-helpers (Th), T-cytotoxic (Tc), T-regulatory
(Treg) or T-memory (Tm) lymphocytes. The B-lymphocytes in the lymph

– 119 –
 nodes and lymphoid follicles differentiate in plasma cells
and B-memory (Bm) lymphocytes. 81
Fig.   69 Monocyte 81
Fig.   70 Thrombocyte 82
Fig.   71 Blood islands 83
Fig.   72 Hematopoiesis 84
Fig.   73 Bundle of smooth muscle cells connected with gap junctions 86
Fig.   74 Smooth muscle cell 87
Fig.   75 Myocyte contraction 87
Fig.   76 Skeletal muscle fascicles 88
Fig.   77 Myofibrils grouped in Cohnheim’s fields, peripheral position of nucleus 88
Fig.   78 Skeletal muscle fiber 89
Fig.   79 Thin myofilament composed of actin and associated proteins 90
Fig.   80 Sarcomere 90
Fig.   81 Contraction of a sarcomere in striated muscle 91
Fig.   82 Ultrastructure of a skeletal muscle fiber 91
Fig.   83 Interaction between actin and myosin filaments 92
Fig.   84 Myosatellite cell 92
Fig.   85 Cardiac muscle 93
Fig.   86 Intercalated disc 94
Fig.   87 Cardiac conducting system 94
Fig.   88 Purkinje fibers 95
Fig.   89 Myoendocrine cell in atrial myocardium 96
Fig.   90 Neuron 97
Fig.   91 Types of neurons 98
Fig.   92 Cell body of a neuron 99
Fig.   93 Axon sheaths 100
Fig.   94 Development of myelin sheath 101
Fig.   95 Node of Ranvier 101
Fig.   96 Grey fibers in PNS (one Schwann cell encloses multiple fibers) 102
Fig.   97 Oligodendrocyte providing a glial sheath and a myelin sheath in CNS 103
Fig.   98 Peripheral nerve 103
Fig.   99 Synapses 104
Fig. 100 Reflex arc 104
Fig. 101 Free nerve endings and Merkel cell 105
Fig. 102 Meissner’s corpuscle in the dermal papilla below the epidermis 106
Fig. 103 Pacinian corpuscle 107
Fig. 104 Muscle spindle 107
Fig. 105 Motor end plate 108
Fig. 106 The Na+/K+ ATPase and ion channels in a membrane of a neuron 109
Fig. 107 Saltatory conduction of action potential between two Ranvier nodes
of a myelinated fiber 109

– 120 –
Fig. 108 Synapse 110
Fig. 109 Neurotransmitter circulation 111
Fig. 110 Astrocytes 112
Fig. 111 Oligodendrocyte and microglia 113
Fig. 112 Ependyma 114
Fig. 113 Satellite cells surrounding a pseudounipolar neuron in a spinal ganglion 115
Fig. 114 Meninges 116

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LITERATURE RECOMMENDED
FOR FURTHER STUDY

Mescher A.L Junqueira’s Basic Histology. Text & atlas. 12th edition. McGraw Hill,
New York, 2010.
Ovalle W., Nahirney P.: Netter´s Essential Histology, 2nd edition, Elsevier, Philadelphia,
2013.
Gartner L.P., Hiatt J.L.: Color Atlas and Text of Histology. 6th edition. Wolters Kluwer,
Baltimore, 2014.
Ross M., Pawlina W.: Histology: a Text and Atlas with Correlated Cell and Molecular
Biology. 6th edition. Wolters Kluwer, Baltimore, 2014.
Young B., Woodford P., O´Dowd G.: Wheater´s Functional Histology. A text and colour
atlas. 6th edition, Churchill Livingstone, Philadelphia, 2013.
Ovalle W., Nahirney P.: Netter´s Histology Flash Card Updated Edition, 1st edition,
Elsevier, Philadelphia, 2013.
Lee L.: Lippincott’s Pocket Histology. Wolters Kluwer, Baltimore, 2014.
Lowe J.S., Anderson P.G. Human Histology, 4th Edition. Elsevier, Philadelphia, 2015.
Berkovitz, B.K.B. – Holand, G.R.: Colour Atlas and Textbook of Oral Anatomy,Histol-
ogy and Embryology 3rd Edition, Elsevier Science, Philadelphia, 2005.
Vaňkhara P., Sedláčková M., Lauschová I., Čech S., Hampl A. Guide to General Histol-
ogy and Microscopic Anatomy. Masaryk University, Brno, 2017.

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