Department of Cell Biology and Histology

Junqueira LC, Carneiro J.

Kierszenbaum,
Abraham L.

Ross MH, Pawlina W.

Gartner LP, Hiatt JL.

 "Histology" - Greek tissue "Histos", and "-logos" = the study of.

Nowadays, the concept includes - understanding of the structure

and function - can better be described as "Microscopic

Anatomy".
(Concise Encyclopedia from Merriam-Webster dictionary)
Branch of biology concerned with the composition and structure of
plant and animal tissues in relation to their specialized functions.
Its aim is to determine how tissues are organized at all structural
levels, from cells and intercellular substances to organs.
involves the use of microscopes as basic tools.

 Cells
Tissues
Organs
Organ Systems

Organism

 Tissues - groups of cells of similar function and origin that

form functional units

Organs - are composed of various tissues.
Organ systems composed of several organs (such as the

gastrointestinal system, respiratory system.....).

 Histology should lighten other disciplines.

Anatomy -- What is the cellular composition of those
structures that you're cutting through?
Physiology -- How are diverse body functions
accomplished by cells, when all cells share a common
set of functions?
Biochemistry -- Where are all those reactions taking
place?
In the long run, it is time-efficient to begin with an

overview of the concepts and appearances associated

with cells and with each of the four basic tissues.

 Knowledge on cellular structure, ultrastructure and

function.
Knowledge on the organization of the four basic tissue

types.
Knowledge on the organization of basic tissues into

organs.
Goal - "reading" tissue specimens on microscope slides

 Because all knowledge is worthwhile, and/or because learning about tissue

composition of the human body is sheer joy.

Because first comes the structure and than the function.

Because some of your patients might expect clear, accurate explanations of

how and why their cells are misbehaving.

Because someday you might become a pathologist, and histology

interpretation is an essential skill.

Because someday you might need to communicate with a pathologist.
Because you want to score well on the U. S. Medical Licensing Exam. -

many USMLE questions

 The body is composed of four basic tissues :

Epithelium - tissue organized as attached sheets of cells

which line or cover and form tubular structures within

organs
Connective Tissue - tissue providing structural and
metabolic support
Muscle Tissue - electrically excitable tissue which
contracts in response to specific stimuli and moves tissues
to which it is attached.
Nervous Tissue - electrically excitable tissue which
receives stimuli, processes them, and transmits signals to
target tissues to integrate the functions of the whole body

12

Location
covers all body surface/lines cavitary organs
forms exo- and endocrine glands.
Origin - in all 3 embryonic layers
endoderm: digestive, respiratory epithelium, thyroid
mesoderm: endothelium, mesothelium
ectoderm: epidermis, adenohypophysis

 Composed of
Cells: compact mass of
specialized cells
Extracellular matrix :
small amount
highly organized basement membrane

HE, ob. 40x

14

Various cell shapes and functions

Avascular
Innervation
Renewal

Metaplasia

15

Cell shapes: flattened, cuboidal, columnar

!!The nuclear form often corresponds to the cell

shape

HE, ob. 40x

17

HE and Blue methylene, ob. 40x

HE, ob. 40x

18

Protection ( epidermis),

Absorption (intestinal epithelium, kidney tubule

epithelium)
Transport
of material at the surface (ciliated epithelia)
across the cell - gas exchange (aveolar epithelium +
endothelium)

Secretion (uni/multicellular glands)

Excretion (kidney tubule epithelium)
Gliding between surfaces (mesothelium)
Contraction : myoepithelial cell

19

Cell polarity: apical/baso-lateral pole

Organelles distribution

Membrane protein distribution membrane domains

Tissue polarity

http://csls-text.c.u-tokyo.ac.jp/active/11_05.html

21

Apical domain
Proteins
Enzymes
Transporters
Channels

Lipids
Cholesterol
Sphingomyelin

Baso-lateral domain
Proteins
Na+/K+ ATP-ase
Transporters (am.ac.,

sugars)
Channels
Receptors
Adhesion proteins
Lipids
Phosphatidylcholine
Phosphatidylinositole

22

23

24

amorphous, PAS + layer beneath

epithelial cells by light microscopy

thicker structure formed by
basal lamina
reticular lamina

25

HE, ob. 40x

http://beyondthedish.wordpress.com/category/lung-treatments/

26

visible only by electron microscopy

a sheet of extracellular material
between epithelial cells and connective tissue
20100 nm thick

lamina densa electron-dense layer - fibrillar

network
laminae lucida - electron-lucent layers on one or
both sides

27

Molecular composition - molecules

secreted by the epithelial cells

type IV collagen in lamina densa
glycoproteins laminin and entactin (nidogen)

- attaching lamina densa to the basal cell

membrane
proteoglycans with heparan-sulfate - perlecan

 Molecules secreted by connective tissue

cells
fibronectin
type VII collagen forming anchoring fibrils

to connective tissue reticular fibers

29

 structural support

selective barrier
regulate cell proliferation and differentiation by

binding and concentrating growth factors;

influence cell metabolism and survival;
organize the proteins in the adjacent plasma
membrane (affecting signal transduction);
pathways for cell migration

 basal laminae to two neighboring epithelia can

fuse or appear to fuse in the absence of

connective tissue
form various barriers or filters

BASAL MEMBRANE
Cell Membrane
(Basal surface
of cell)

Lamina Lucida

Lamina Densa
Lamina Reticularis

35

Apical pole
Cilia, stereocilia, microvilli

Baso-lateral pole
Lateral interdigitations
Basal labyrinth
Basal lamina

36

HE, ob. 40x

Brush border

37

anatomyatlases.org

Pseudostratified columnar
with cilia

Pseudostratified columnar
with stereocilia

MICROVILLI

CILIA

39

40

HE, ob. 100x

Stria vascularis

HE, ob. 100x

42

free nerve endings - unmyelinated axons

depends on location of the epithelium and

its exposure to stimuli

43

Epithelia continuously renew their cell

population
Different rates: fastest small intestine,

slowest- skin

HE, ob. 100x

HE, ob. 100x

HE, ob. 40x

HE, ob. 100x

47

Self-renewal

Assimetric division

Multipotency

Hayward P et al. Development 2008;135:411-424

48

Sheading cells

Differentiated cells
Goblet

Vilus

Enteroendocrine

Enterocyte

Differentiation
and migration
24-48h

Crypt

Mitotic activity
24-36h
Lamina propria

Progenitor cells

Stem cells
Paneth cells

INPUTS FEEDING BACK ON STEM-CELL

FUNCTION IN THE NICHE
constraints of the architectural space
physical engagement of the cell
membrane with neighboring cells or
surfaces
signaling interactions at the interface of
stem cells and niche or descendent cells
paracrine and endocrine signals from

local or distant sources

neural inputs and metabolic products of
tissue activity

Scadden DT. The stem-cell niche as an entity of action. Nature. 2006; 441(7097):1075-9.

Jones LD, Wagers AJ.

No place like home: anatomy and function of the stem cell niche.
Nat Rev Mol Cell Biol. 2008; 9(1):11-21.

51

Metaplasia
transformation into

another type of
mature epithelium,
in pathological
circumstances

Metaplasia
Tissue

Normal

Metaplasia

Stimulus

Bronchi

Pseudostratifi
ed epithelium

Squamous
epithelium

Cigarette smoke

Urinary
bladder

Transitional
epithelium

Squamous
epithelium

Chronic vitamin
A deficiency

Esophagu
s

Squamous
stratified
nonkeratinize
d epithelium

Columnar
epithelium

Gastroesophageal
reflux

53

54

HE, ob. 40x

Histology for Pathologists

Authors: Mills S. E. Sternberg S.
Published year: 2004

55

Covering epithelia covering external

surface of the body or lining cavities of

internal organs
Glandular epithelia - forming secretory part
of exo and endocrine glands
Sensorial epithelia

 Separates two different environments

Active barrier
complete sealing (epidermis)
limited permeability (mucosa-lining epithelia)

Classification based on number

of cell layers.
Apical surface

Basal surface

Squamous

Simple
Apical surface

Basal surface
Stratified

Cuboidal

Columnar
Classification based on cell shape.

 Simple/stratified
squamous
Simple/stratified
cuboidal
Simple/stratified
columnar
Pseudostratified
Transitional/urothelium

 Distribution:
endothelium,
mesothelium
Bowmanns capsule

Silver staining, ob. 40x

Bowmanns capsule

Functions:
flitration
diffusion
osmosis
secretion - serosa
http://imc02.hccs.edu/BiologyLabs/AP1/03Tissues/003EpithelialIndex.html

62

07:14

A, Scanning electron micrograph of well-preserved endothelium.

http://www.comprehensivephysiology.com/WileyCDA/CompPhysArticle/refId-cp02020

Copyright American Heart Association

Roubos N et al. Circulation 1995;92:31-36

64

09:58

Endothelial
cells have
both
metabolic
and synthetic
functions.

2004 by Oxford University Press

Galley H F , and Webster N R Br. J. Anaesth. 2004;93:105-113

 Distribution:
kidney tubules
excretory ducts of
exocrine glands
(intercalated ducts),
covering epithelium of
the ovary
Tubular epithelium,
kidney

http://imc02.hccs.edu/BiologyLabs/AP1/03Tissues/00
3EpithelialIndex.html

Functions:
secretion
absorption

 Distribution:
digestive tract,

fallopian tubes,
excretory ducts of

salivary glands
Intestinal epithelium

apical surface

specializations:
cilia,
microvili

 Functions:

absorption
secretion
Eg. mucus, enzymes

transport on the

surface - ciliary
action

 Distribution:
respiratory epithelium
male reproductive
system

Functions:
Respiratory epithelium secretion goblet cells
clearance
ciliated cells
absorption
- stereocilia
http://imc02.hccs.edu/BiologyLabs/AP1/03Tissues/003EpithelialIndex.html

 apical surface

specializations:
cilia,
stereocilia

Respiratory epithelium

HE, ob. 40x

Epididymis epithelium

 Distribution:
sweat glands
excretory duct
Function
protection
secretion

HE, ob. 100x

Sweat gland

 Distribution:
ocular conjunctiva,
large ducts of salivary glands
Functions:
protection
absorption

HE, ob. 40x

Salivary gland - duct

http://imc02.hccs.edu/BiologyLabs/AP1/03Tiss
ues/003EpithelialIndex.html

 Distribution:
digestive tract mouth to esophagus,
vagina,
anterior cornea

Functions

protection, in

areas subjected
to abrasion

HE, ob. 40x

Esophageal epithelium

 protection, in areas

subjected to
abrasion
prevents water loss

HE, ob. 40x

75

keratinocytes
continuous turnover (renewal) of the epithelium by

passing through 4 overlapping processes:

cell renewal, or mitosis;

differentiation, or keratinization;
cell death
exfoliation

the entire process takes 15-30 days and occurs in

waves.
a cell layer produced by a mitotic wave in the basal
layer undergoes keratinization in synchrony.
each wave pushes the cell layers produced in earlier
waves toward the surface.

76

filagrin
Filagrin
Filam.
Filam.
de
de
keratin
keratin

Descrcare
corpi
lamelari

Corpi
lamelari

 Distribution:
urinary excretory tract (from proximal
ureter to proximal urethra)
Functions:
stretches - allows organs to distend
protective - osmotic barrier
HE, ob. 40x

HE, ob. 100x

 Cells:
basal cells
racket- shaped cells
umbrella-like cells

http://imc02.hccs.edu/BiologyLabs/AP1/03Tissu
es/003EpithelialIndex.html

Guangwei Min, Ge Zhou, Matthieu Schapira, Tung-Tien Sun and XiangPeng Kong - Structural basis of urothelial permeability barrier function
as revealed by Cryo-EM studies of the 16 nm uroplakin particle Journal of Cell Science 116 (20), 2003

 Definition: one or more epithelial cells highly

specialized for secretion

Gland: group of various epithelial cells that

synthesize, store and/or secrete a specific secretion

product.
The secretory process has 4 phases:
Assimilation

Synthesis
Storage
Secretion

 Criterion - release of secretory product

exocrine glands
in contact with the free surface of
epithelium by an excretory duct;
eliminates secretory product through an
excretory duct

endocrine glands
no connection with the surface; completely
surrounded by connective tissue;
eliminates secretory product directly into
the blood stream

Classification:
By cell grouping
By chemical structure of secretory product
By moment of release of secretory product

By range of action of secretory product

Cell grouping:

anastomosing cords, intercalated with

capillaries
follicles: cavities filled with acellular material,
lined by epithelial cell.
islets : endocrine cells grouped in islands,
surrounded by exocrine or connective cells
isolated cells: Diffuse Neuro-Endocrine
System (DNES)

Chemical structure of secretory product:

Small polypeptides: Diffuse Neuro-Endocrine

System (DNES)
Proteins and large polypeptides: parathyroid
Cholesterol-derived : adrenal cortex

Moment of release of secretory product

immediate release: adrenal cortex
after storage
intracellular

extracellular: thyroid follicles

By range of action of secretory product

Autocrine glands: on itself
Paracrine glands: small range action -neighbor

cells
Endocrine glands: at distance

Classification:

By structure
By chemical composition of secretory product
By secretion mechanism

Classification
Number of cells
unicellular gland (goblet cell)

multicellular gland
Structure of excretory duct
Structure of the secretory
portion - adenomer

HE, ob. 100x

PAS, ob. 100x

Excretory duct
simple: unbranched
compound: branched

Secretory segment
tubular
coiled tubular
branched tubular
acinar
branched acinar
mixt: tubuloacinar

MORPHOLOGY OF EXOCRINE GLANDS

= DUCTS
= GLANDS

 Simple tubular : Lieberkuhn glands

Simple coiled tubular: sweat gland
Simple branched tubular: gastric glands
Simple acinar: lacrimal gland
Simple branched acinar: sebaceous gland

 compound acinar: parotid glands

compound tubuloacinar: sublingual, submandibular

glands
compound tubuloalveolar: prostate

 mucous glands: secretory product rich in

glycoproteins (mucus); highly viscous

serous glands: protein secreting cells
mixed glands

 Merocrine secretion: exocytosis of stored

secretory granules
Apocrine secretion: secretion of product along

with apical cytoplasm

Holocrine secretion: destruction of entire cell

during secretion

Merocrine

Apocrine

Holocrine

 Ion-transporting cell
Protein-secreting cell

Mucus-secreting cell
Lipid-secreting cell
Myoepithelial cells

 Reabsorbtion:
Secretion:
uriniferous tubules,
endothelial cells ciliary
processes,
excretory ducts, salivary glands
ependymal cells - choroid
digestive tract
plexus

microvilli

Tight junction

interdigitations

Basal labirinth

Secretory cycle

Polarity:
basal pole: rich RER
round nucleus,
centrally/lower half
Golgi above the nucleus
apical pole: zymogen
granule
Secretion:
enzymes (pancreas, salivary
glands)
hormones (paratyroid PTH)

Serous acinus

 Diffuse neuro-endocrine system (DNES)

Isolated/groups scattered in epithelia

Digestive tract
Respiratory epithelium
Thyroid/parathyroid glands
Urinary and genital system
Special techniques for light microscopy
AgNO3 silver precipitate - ARGENTAFFINE CELLS
K2Cr2O7 oxidation CROMAFFINE CELLS
Immunocytochemistry NSE/secreto-chromogranine

108

Digestive tract
entero-endocrine cells:
somatostatin (D cells)
VIP (D1 cells)
serotonin (EC cells)
colecistochinin (I cells)
GIP (K cells)
enteroglucagon (L
cells)
motilin (Mo cells)
neorotensin (N cells)
secretin (S cells)

109

 Polarity:
basal pole: nucleus,
organelles
apical pole: secretory
granules
Location:
Mucus-secreting cells
Goblet cells
intestinal and respiratory epithelia,
Mucous acini - salivary glands
Gastric epithelium

Hormone-secreting cells
Adenohypophysis -

 Location:
Exocrine cells
Sebaceous gland

Endocrine cells
Leydig cells - testis
Follicular cells - ovary
Adrenal cortex cells

113

114

 Location:
surrounding secretory portion of
Salivary glands
Lacrimal glands
Sweat glands
Mammary glands

 Features:
Cytokeratin filaments

epithelial tissue
Contractile filaments muscle
tissue
GAP junctions synchronizing
Desmosomes with epithelial
cells
Hemidesmosomes with BM