• Histology [Gr.

, 􏰚 􏰚 􏰚 ó􏰚 , histos 􏰚 tissue; 􏰚 􏰚 􏰚 í􏰚 , logia 􏰚

science], also called microscopic anatomy, is the scientific study of
microscopic structures of tissues and organs of the body.
• Modern histology is not only a descriptive science but also includes
many aspects of molecular and cell biology, which help describe cell
organization and function.
• Light microscopy (for viewing glass slides) and virtual microscopy (for
viewing digitized microscopic specimens on a computer screen or
mobile device) are the most commonly taught methods for examining
cells, tissues, and organs in histology courses
• Histochemical and cytochemical procedures are based on specific binding of a
dye with a particular cell component exhibiting inherent enzymatic activity.
• Eosin is an acidic dye (pink) and carries a net negative charge. It reacts with
positively charged cationic groups in cells and tissues, particularly amino groups
of proteins (eosinophilic structures).
• Hematoxylin acts as a basic dye (blue) and carries a net positive charge. It reacts
with negatively charged ionized phosphate groups in nucleic acids (basophilic
structures)
• The periodic acid–Schiff (PAS) reaction stains carbohydrates and carbohydrate-
rich molecules a distinctive magenta color. It is used to demonstrate glycogen in
cells, mucus in cells and tissues, the basement membrane, and reticular fibers in
connective tissue
Tissues: Concept and
Classification
Refuerzo, VR, MD, DPBS,FPSCRS
General Surgery
Subspecialty: Colorectal Surgery
HISTOGENESIS OF TISSUES

• Three germ layers that give rise to all tissues and organs include the ectoderm,
mesoderm, and endoderm.
• Ectodermal-derived structures develop either from surface ectoderm or
neuroectoderm.
• Surface ectoderm gives rise to epidermis (and its derivatives), cornea and lens epithelia of
the eye, enamel of the teeth, components of the internal ear, adenohypophysis, and mucosa
of the oral cavity and lower part of the anal canal.
• Neuroectoderm gives rise to the neural tube, the neural crest, and both their derivatives.
• Mesoderm gives rise to connective tissue; muscle tissue; heart, blood, and lymphatic
vessels; spleen; kidneys and gonads with genital ducts and their derivatives; mesothelium,
which lines body cavities; and the adrenal cortex.
• Endoderm gives rise to alimentary canal epithelium; extramural digestive gland epithelium
(liver, pancreas, and gallbladder); epithelium of the urinary bladder and most of the urethra;
respiratory system epithelium; thyroid, parathyroid, and thymus gland; parenchyma of the
tonsils; and epithelium of the tympanic cavity and auditory (Eustachian) tubes.
EPITHELIAL TISSUE
OUTLINE
• Introduction
• Principal functions of epithelial tissue
• Characteristics of epithelial tissue
• Basement membrane
• Intercellular adhesions and other junctions
• Specializations of the apical cell surface
• Covering Epithelia
• Secretory epithelia
• Transport across epithelia
• Renewal of Epithelial Cells
OVERVIEW OF EPITHELIAL STRUCTURE AND FUNCTION

• Epithelium is an avascular tissue composed of cells that cover the

exterior body surfaces and line internal closed cavities (including the
vascular system) and body tubes that communicate with the exterior
(the alimentary, respiratory, and genitourinary tracts).
• It forms the secretory portion (parenchyma) of glands and their
ducts.
• Receptors for the special senses (smell, taste, hearing, and vision).
• Selective barrier between the external environment and underlying
connective tissue.
CHARACTERISTICS OF EPITHELIAL TISSUE
• Nuclear shape corresponds
roughly to cell shape:
• Tall cells have elongated nuclei
• Squamous cells have flattened
nuclei
• Cuboidal or pyramidal cells
usually have more spherical nuclei
CHARACTERISTICS OF EPITHELIAL TISSUE
• Most epithelia rest on connective tissue that contains the
microvasculature bringing nutrients and O 2 to both tissues.
• LAMINA PROPRIA
• The connective tissue that underlies the epithelia lining the organs of the
digestive, respiratory, and urinary systems.
• PAPILLAE
• The area of contact between the epithelium and connective tissue may be
increased by irregularities at the interface in the form of small appendages
• occur most frequently in epithelial tissues subject to friction, such as the
covering of the skin or tongue
CHARACTERISTICS OF EPITHELIAL TISSUE
• Epithelial cells generally show polarity, with organelles and
membrane proteins distributed unevenly within the cell.
• The region of the cell contacting the connective tissue is called the
basal pole
• The opposite end, usually facing a space, is the apical pole. The two
poles of epithelial cells differ in both structure and function.
Epithelial cells have 3 principal characteristics:

• cell junctions;

• exhibit functional and

morphological polarity

• basement membrane.
PRINCIPAL FUNCTIONS OF EPITHELIAL TISSUE
Covering, lining,
and protecting Absorption
surfaces (intestinal lining)
(epidermis)

Secretion
(parenchymal cells
of glands)
Classification of Epithelium.
# of cell layers and the shape of the surface cells
• simple when it is one cell layer thick
• stratified when it has two or more cell layers.
• The individual cells that compose an epithelium are described as:
• squamous when the width of the cell is greater than its height;

• cuboidal when the width, depth, and height are approximately the same;

• columnar when the height of the cell appreciably exceeds the width
• In a stratified epithelium, the
shape and height of the cells
usually vary from layer to layer,
but only the shape of the cells
that form the surface layer is
used in classifying the
epthelium.
Epidermis Oral cavity Esophagus
Vagina
Barrier and Protection
Specialization of the apical cell surface domain
Special classifications of epithelium

• Pseudostratified epithelium
appears stratified.
• It is a simple epithelium with all
cells resting on the basement
membrane but not all extending
to the free epithelial surface.
• Trachea and bronchial tree Ductus
deferens
Efferent ductules of epididymis
• Secretion and conduit Absorption
and conduit
Special classifications of epithelium

• Transitional epithelium
(urothelium) is stratified and
lines the lower part of the
urinary tract.
• Cells on its free surface layer
transition from large, round,
dome-shaped cells to squamous
cells depending on the urinary
organ distention.
• Renal calyces Ureters Bladder
Urethra
• Barrier, distensible property
Epithelial metaplasia
• is a reversible conversion of one mature epithelial cell type to another
mature epithelial cell type.
• Metaplasia is generally an adaptive response to stress, chronic
inflammation, or other abnormal stimuli.
• The original cells are substituted by cells that are better suited to the
new environment and more resistant to the effects of abnormal
stimuli.
• Metaplasia results from reprogramming of epithelial stem cells that
changes the patterns of their gene expression.
Metaplasia

• The most common epithelial metaplasia is columnar- to-squamous

and occurs in the glandular epithelium, where the columnar cells
become replaced by the stratified squamous epithelium.
• Squamous metaplasia frequently occurs in the pseudostratified
respiratory epithelium of the trachea and bronchi in response to
prolonged exposure to cigarette smoke.
• Simple columnar epithelium of the cervical canal is replaced by the
stratified squamous nonkeratinized epithelium
• Squamous-to-columnar epithelial metaplasia may also occur. For
example, as a result of gastroesophageal reflux (Barrett’s esophagus),
the stratified squamous non- keratinized epithelium of the lower part
of the esophagus can undergo metaplastic transformation into an
intestinal- like simple columnar epithelium containing goblet cells.
• If abnormal stimuli persist for a long time, squamous metaplastic cells
may transform into squamous cell carcinoma. Cancers of the lung,
cervix, and bladder often originate from squamous metaplastic
epithelium. Squamous columnar epithelium may give rise to
glandular adenocarcinomas.
CHARACTERISTICS OF EPITHELIAL TISSUE
• The shapes and dimensions of epithelial cells are quite variable,
ranging from tall columnar to cuboidal to low squamous cells.
• The cells’ size and morphology are generally dictated by their
function.
• Epithelial cell nuclei vary in shape and may be elliptic (oval),
spherical, or flattened.
• Endothelium and mesothelium are the simple squamous epithelia
lining the vascular system and body cavities.

• Endothelium is the epithelial lining of the blood and lymphatic vessels.

• Endocardium is the epithelial lining of ventricles and atria of the heart.

• Mesothelium is the epithelium that lines the walls and covers the contents of
the closed cavities of the body (i.e., the abdominal, pericardial, and pleural
cavities )
Diverse epithelial functions can be found in
different organs of the body.
Absorption and secretion
Secretion
Absorption

• Small intestine and colon

• Stomach lining and gastric glands
• Gallbladder
• transportation, as in the transport of materials or cells along the
surface of an epithelium propelled by motile cilia (transport of dust
particles in the bronchial tree) or in the transport of materials across
an epithelium (pinocytosis or endocytosis) to and from the
connective tissue;
• mechanical protection, as in the stratified squamous epithelium of
the skin (epidermis) and the transitional epithelium of the urinary
bladder; and
• receptor function to receive and transduce external stimuli, as in the
taste buds of the tongue, olfactory epithelium of the nasal mucosa, and
the retina of the eye.
CELL POLARITY
• Apical Domain
• Lateral Domain
• Basal Domain
SPECIALIZATIONS OF THE APICAL CELL
SURFACE

Microvilli Sterocilia

Cilia
APICAL DOMAIN

• Microvilli are small, finger-like cytoplasmic processes containing a core of actin

filaments. They increase the apical surface area for absorption and are visible in LM
as striated or brush borders.
• Stereocilia (stereovilli) are long microvilli with limited distribution to the male
reproductive system (absorption) and sensory epithelium of the inner ear (sensory
mechanoreceptors).
• Motile cilia are hair-like extensions of apical plasma membrane containing an
axoneme, a core of microtubules in a 9 􏰚 2 arrangement. Cilia movement originates
from the coordinated sliding of microtubule doublets generated by the activity of
dynein, a microtubule-based motor protein.
• Primary cilia (monocilia) have a 9 􏰚 0 microtubule arrangement, are immotile, and
function as chemo-, osmo-, and mechanosensors. They are present on almost all
eukaryotic cells.
1. MICROVILLI
• in epithelial cells specialized for
absorption, the apical surfaces present an
array of projections called microvilli
• In cells such as those lining the small
intestine, apical surfaces are densely
covered with uniform microvilli, which
are visible as a brush or striated border
on these cells.
• The average microvillus is about 1 μm
long and 0.1 μm wide, but with hundreds
or thousands present on the end of each
absorptive cell, the total surface area can
be increased by 20- or 30-fold.
Medical Application
• Celiac disease, also called gluten-sensitive enteropathy
or sprue, is a disorder of the small intestine in which one of the first
pathologic changes is loss of the microvilli brush border of the
absorptive cells.
• This is caused by an immune reaction against the wheat protein
gluten during its digestion, which produces diffuse enteritis (intestinal
inflammation), changes to the epithelial cells leading
to malabsorption, and eventually to pathologic changes in the
intestinal wall.
• The malabsorption problems and structural changes are reversible
when gluten is removed from the diet.
2. STEROCILIA • restricted to absorptive epithelial
cells lining the epididymis and the
proximal part of ductus deferens in
the male reproductive system.
• stereocilia increase the cells’ surface
area, facilitating absorption.
• More specialized stereocilia with a
motion-detecting function are
important components of inner ear
sensory cells.
• Longer and much less motile than
microvilli, and may show distal
branching along their length.
3. CILIA
• are long projecting structures,
larger than microvilli, which
contain internal arrays of
microtubules
• Most (if not all) cell types have at
least one cilium of variable length,
usually called a primary cilium
• not motile but is enriched with
receptors and signal transduction
complexes for detection of light,
odors, motion, and flow of liquid past
the cells.
3. CILIA
• Motile cilia
• are found only in epithelia, where they are abundant on the apical domains
of many cuboidal or columnar cells.
• Typical cilia are 5-10 μm long and 0.2 μm in diameter
• Immotile Cilia Syndrome / Kartagener syndrome
• Several mutations have been described in the proteins of the cilia and flagella
• symptoms are chronic respiratory infections caused by the lack of the
cleansing action of cilia in the respiratory tract and immotile spermatozoa,
causing male infertility.
THE LATERAL DOMAIN AND ITS SPECIALIZATIONS IN CELL-TO-
CELL ADHESION

• The lateral domain is

characterized by the presence of
cell adhesion molecules (CAMs)
that form junctional complexes
(occluding, anchoring, or
communicating junctions)
between the apposed lateral
domains of neighboring cells.
TIGHT JUNCTION (ZONULA OCCLUDENS)
• are the most apical of the junctions
• The term “zonula” indicates that the
junction forms a band completely
encircling each cell
• The seal between the membranes is
due to interactions between the
transmembrane proteins claudin and
occludin of each cell
• The intercellular seal of this junctional
type ensures that molecules crossing
an epithelium in either direction do so
by going through the cells
(transcellular path) rather than
between them (paracellular
pathway).
Zonula occludens strands

• Occludin, a 60 kDa protein, participates in maintaining the barrier

between adjacent cells as well as the barrier between the apical and
lateral domains .
• Claudins form the backbone of each strand. In addition, claudins
(especially claudin-2 and claudin-16) are able to form extracellular
aqueous channels for the paracellular passage of ions and other small
molecules.
• Junctional adhesion molecule (JAM) is a 40 kDa protein that belongs
to the immunoglobulin superfamily (IgSF).
• The cytoplasmic portions of all
three proteins contain a unique
amino acid sequence that
attracts regulatory and signaling
proteins called PDZ-domain
proteins.
• These proteins include the
zonula occludens proteins ZO-1,
ZO-2, and ZO-3
Medical applications

• A mutated form of claudin-14 causes an increased permeability of

zonula occludens in the organ of Corti (receptor of hearing), affecting
generation of action potentials.
• Many pathogenic agents, such as cytomegalovirus and cholera toxins,
act on ZO-1 and ZO-2, causing the junction to become permeable.
• Parasite The common house dust mite, Dermatophagoides
pteronyssinus, also destroys zonula occludens junctions. ASTHMA
TIGHT JUNCTION (ZONULA OCCLUDENS)
MEDICAL APPLICATION
• The enterotoxin secreted by Clostridium perfringens, which causes
“food poisoning,” binds claudin molecules of intestinal cells, prevents
insertion of these proteins during maintenance of tight junctions, and
causes loss of tissue fluid into the intestinal lumen via the paracellular
pathway.
• Helicobacter pylori, which is important in the etiology of gastric
ulcers and gastric carcinoma binds the extracellular domains of tight-
junction proteins in cells of the stomach and inserts a protein into
these cells, which targets ZO-1 and JAM and disrupts signaling from
the junction.
• Viruses ( infant enteritis)
Anchoring Junctions
• Anchoring junctions (zonula adherens and macula adherens) provide
adhesions between epithelial cells using CAMs that are linked to the
cytoskeleton of adjacent cells.

• All anchoring junctions utilize calcium-dependent cadherins family of proteins.

• The zonula adherens encircles the cell just below its tight junction and is composed of E-
cadherin–catenin complexes that interact with actin filaments.

• The macula adherens (desmosome) provides a scattered, localized, spot-like junction

and is composed of desmogleins and desmocollins that attach to the desmosomal
plaques anchoring the intermediate filaments.
Anchoring Junctions
• Zonula Adherens

• Couples the actin cyto- skeleton to

the plasma membrane at regions
of cell–cell adhesion
Anchoring Junctions
• Macula adherens (desmosome)

• Couples the intermediate

filaments to the plasma
membrane at regions of cell–cell
adhesion
DESMOSOME (MACULA ADHERENS)
MEDICAL APPLICATION
• Various blistering (bullous) diseases, such as pemphigus vulgaris,
involving the epidermis or stratified squamous epithelia of the oral
mucosa, are due to abnormal desmosome function caused by
autoimmune reactions against specific desmogleins that reduce cell-
to-cell adhesion.
HEMIDESMOSOMES
• These adhesive structures
resemble a half-desmosome
ultrastructurally, but, unlike
desmosomes, they contain
abundant integrins rather than
cadherins.
• The transmembrane integrin
proteins bind the extracellular
macromolecules laminin and
collagen type IV.
Communicating junctions
• Communicating (gap) junctions
consist of an accumulation of
transmembrane channels (formed by
two half-channels, the connexons) in
a tightly packed array.
• They allow for the exchange of ions,
regulatory molecules, and small
metabolites between cells
BASAL DOMAIN: BASEMENT MEMBRANE AND
CELL-TO-EXTRACELLULAR MATRIX ADHESION

• The basement membrane is a specialized structure located next to

the basal domain of epithelial cells and the underlying connective
tissue stroma.
• Cell-to-extracellular matrix junctions anchor the cell to the
extracellular matrix; they are represented by focal adhesions and
hemidesmosomes.
•
Basal cell membrane infoldings increase the cell surface area and
facilitate morphologic interactions between adjacent cells and
extracellular matrix proteins.
Basement membrane
• The basal lamina is the
structural attachment site for
overlying epithelial cells and
underlying connective tissue.
• contains molecules that come
together to form a sheet-like
structure.
BASEMENT MEMBRANE
• The basement membrane may be
resolved into two structures.
• BASAL LAMINA
• Nearest the epithelial basal poles is an
electron-dense layer,
• 20-100 nm thick, consisting of a network of BL
fine fibrils Beneath this
• RETICULAR LAMINA RL

• layer of often a more diffuse and fibrous

COMPONENTS OF BASAL LAMINAE
• Laminin
• These are large glycoproteins that self-assemble as a lacelike
network immediately below the cells’ basal poles where they are
held in place by the transmembrane integrins
• Type IV collagen
• Monomers of type IV collagen contain three polypeptide chains
and self-assemble further to form a feltlike layer.
• The laminin and type IV collagen networks are held together by the
adhesive glycoprotein entactin/ nidogen, and by perlecan, a
proteoglycan.
FUNCTIONS OF BASEMENT MEMBRANE

Provide
Provide polarity
structural
to epithelial cells
support

Attach epithelia
to underlying
connective tissue
Glands
• Exocrine glands
• secrete their products directly onto a surface or through epithelial ducts that
may modify their secretion
(concentrating, removing, or adding substances)

• Endocrine glands
• lack a duct system.
• secrete their hormones into the connective tissue, from which they enter the
bloodstream to reach their target cells.
Exocrine Glands
 MECHANISMS BY WHICH MULTICELLULAR GLANDS
RELEASE THEIR PRODUCTS:
• This is the most common method of protein secretion and involves typical exocytosis of
Merocrine protein or glycoproteins from membrane-bound vesicles (pancreatic acinar cell)

• The secretory product accumulates within the maturing cell, which simultaneously un-
dergoes destruction orchestrated by programmed cell death pathways. (sebaceous
Holocrine
gland;tarsal glands of eyelid.)

• Here product accumulates at the cells’ apical ends, portions of which are then extrude
to release the product together with a bit of cytoplasm and plasma membrane. This is
Apocrine the mechanism by which droplets of lipid are secreted in the mammary gland
SECRETORY EPITHELIA AND GLANDS
• Glands can be simple (ducts not branched) or compound (ducts with
two or more branches).
• Secretory portions can be tubular (either short or long and coiled) or
acinar (rounded and saclike); either type of secretory unit may be
branched, even if the duct is not branched.
• Compound glands can have branching ducts and can have multiple
tubular, acinar, or tubuloacinar secretory portions
Unicellular glands
• Scattered secretory cells,
sometimes called unicellular
glands, are common in simple
cuboidal, simple columnar, and
pseudostratified epithelia of
many organs.
• EX: goblet cell abundant in the
lining of the small intestine and
respiratory tract, which secretes
lubricating mucus that aids the
function of these organs.
Goblet cell
Multicellular glands
SECRETORY EPITHELIA AND GLANDS
• Exocrine glands with merocrine secretion can be further categorized
as either serous or mucous according to the nature of their secretory
products, which give distinct staining properties to the cells.
• Serous cells
• synthesize proteins that are mostly nonglycosylated, such as digestive
enzymes (watery)
• stain intensely with basophilic or acidophilic stains.
• Ex: Acini of the pancreas and parotid salivary glands
• Mucous cells
• such as goblet cells, also have RER and Golgi complexes and are filled apically
with secretory granules, but these contain heavily glycosylated proteins called
mucins .( viscous and slimy,)
Mucous / serous secreting glands
RENEWAL OF EPITHELIAL CELLS
• Epithelial tissues are relatively labile structures whose cells are
renewed continuously by mitotic activity and stem cell populations.
• The replacement cells are produced by mitotic division of adult stem
cells residing in different sites (niches) in various epithelia.
• The rate of renewal varies widely; it can be fast in tissues such as the
intestinal epithelium, which is replaced every week, or slow, as in the
large glands.
• In stratified epithelial tissues, stem cells and mitosis occur only within
the basal layer in contact with the basal lamina.
RENEWAL OF EPITHELIAL CELLS
• Epithelia are normally capable of rapid repair and replacement of
apoptotic or damaged cells.
• In some large glands, most notably the liver, mitotic activity is
normally rare but is actively renewed following major damage to the
organ.
• When a portion of liver tissue is removed surgically or lost by the
acute effects of toxic substances, cells of undamaged regions quickly
begin active proliferation and a mass of liver tissue with normal
function is regenerated.
iPS
• Recent discovery and generation of induced pluripotent stem (iPS) cells
from human keratinocytes demonstrates that somatic adult cells can be
reprogrammed to a pluripo tent state by the enforced expression of several
embryonic transcription factors
• . Keratinocyte-derived iPS cells appear to have identical morphological and
functional characteristics to human embryonic stem cells.
• In the future, iPS cells may play an important role for both custom-tailored
cell therapy (homologous cell recombination and transplantation) and
disease modeling.
• This involves generating iPS cells from a patient’s epidermis, which can be
further differentiated in vitro into disease-affected cell types and tested for
responses to novel drug therapies.