UST FACULTY OF MEDICINE AND SURGERY

Class of 2016

Histology
First Shifting Reviewer

Cytoplasm

CELL STRUCTURE AND FUNCTION

Histology: study of normal structure

Cell: functional unit of all living organisms
Eukaryote: have defined nucleus enclosed by a
membrane
Prokaryote: lacks membrane-bound organelles

Nucleus

Membrane Structure

Plasmalemma: outer limiting membrane

Davson and Danieli: Classical Model
o Trilaminar appearance of 2 protein
layers sandwiching a lipid layer
Singer and Nicholson: Fluid Mosaic Model
o Phospholipid amphipathic bilayer, with
a hydrophilic head and a non-polar
hydrophobic tail
o Polar head: glycerol conjugated to a
nitrogenous compound
o Non-polar tail: two long-chain fatty
acids (one unsaturated, one saturated)
o Fluidity and flexibility is due to
presence of unsaturated fatty acids
and cholesterol
Integral proteins
o Incorporated within the membrane
o Transmembrane if it spans the entire
thickness of the membrane
Peripheral proteins
o Held to inner and outer surfaces by
weak electrostatic forces
Glycocalyx
o Glycoproteins and glycolipids
projecting from the surface of the
bilayer forming an outer coating
involved in protection, cell recognition,
formation of intercellular adhesions,
and adsorption of molecules
o Role in histocompatibility
Functions
o Filtration barrier
o Ion permeability
o Receptor sites
o Cell recognition
o Pinocytosis/ phagocytosis/ exocytosis

Ground substance subdivided into:

o Endoplasm: manifest active streaming
with cell components carried along
o Exoplasm: gel-like

Largest organelle; found in all cells except RBC

Control center of the cell
Types:
o Pyknotic Nucleus: small, condensed
o Chromatic Nucleus: blotchy
o Vesicular Nucleus: cleared out
appearance
Contents:
o Chromatin

Contains DNA and proteins

Heterochromatin: tightly
coiled inactive chromatin
found in irregular clumps (in
females, Barr Body exist as
inactivated X chromosomes)

Euchromatin: electronluscent, active in RNA

synthesis
o Nucleoprotein

Synthesis in the cytoplasm

and imported to the nucleus

Histone proteins: LMW,

positively charged, bind
tightly to DNA and control
coiling and expression of
genes

Non-Histone: enzymes for

the synthesis of DNA and
RNA
o RNA

mRNA, tRNA, rRNA

Nucleolus and Protein Synthesis

Nucleoli are sites of RNA synthesis and ribosome

assembly
o Filamentous components: sites of
ribosomal RNA synthesis
o Granular components: sites of
ribosome assembly
Intensely basophilic
o Pars Amorpha/ Pars Fibrosa

Closely packed filaments on

interior
o Nucleolonema/ Pars Granulosa

Surrounds pars amorpha,

reticulum of anastomosing
strands

By: Sachi Estreller |Section B

UST FACULTY OF MEDICINE AND SURGERY

Class of 2016

Protein Synthesis
o Transcription: DNA template copied to
form a complementary mRNA
o Introns (non-coding sequences) are
spliced out of the mRNA before
passing through the nuclear pore
complex
o Translation: mRNA binds to ribosomes
that read the sequence and make a
chain of AAs for a particular protein
Ribosomes
o Composed of a strand of RNA with
associated ribosomal proteins
o Aligns mRNA so that tRNA will be
brought into position and AAs are
added sequentially to form protein
o Polyribosomes: ribosomes attached to
mRNA
o Ribosomes in RER

Proteins are folded to form

tertiary structure, intrachain
disulphide bonds are formed
and first steps of
glycosylation take place

Lysosomal proteins, proteins

for export, and integral
membrane proteins are
made
o Free Ribosomes

Proteins destined for the

cytoplasm, nucleus, and
mitochondria are produced

Nuclear Envelope

Thicker than cell membrane

Consist of 2 membranes enclosing a narrow
perinuclear space that communicates with
cisternae of RER
Inner and outer layers have phospholipid bilayer
with different integral proteins
Outer lipid bilayer
o Continuous with RER
Inner lipid bilayer
o Contains the nuclear lamina, a layer of
intermediate filaments that consist of
lamins that link inner membrane
proteins and heterochromatin
Nuclear pore
o Contains a nuclear pore complex,
cylindrical structure consisting of 50
proteins forming a central pore
o Permit the exchange of metabolites,
macromolecules and ribosomal
subunits
o Hold together the two lipid bilayers

Endoplasmic Reticulum

Most abundant organelle

May have flattened and tubular cisterns

Rough Endoplasmic Reticulum

With ribosomes

Active in protein synthesis

Smooth Endoplasmic Reticulum

Without ribosomes

Active in lipid synthesis and membrane synthesis

and repair

Synthesize cholesterol and phospholipids (FAs,

and triglycerides are synthesized in cytoplasm)

Found in the liver

o Rich in cytochrome P450 and plays a
role in the metabolism of glycogen and
detoxification of metabolic byproducts

Found in muscle
o Called sarcoplasmic reticulum
o Involved in storage and release of
calcium

Golgi Apparatus

Stacked, saucer-shaped, membrane-bound

cisternae
Cis: convex, forming face
Trans: concave, maturing face
Process:
o Proteins synthesized in RER
transported to cis Golgi face in coated
vesicles (coat protein is called COP II)
o Coat proteins disengage and fuse with
the cis face
o Proteins are passed from cistern to
cistern by COP I coat proteins
o Glycosylation of proteins is completed
by sequential addition of sugar
residues and the proteins are packaged
for transport to their final destination
o At the trans face, proteins are sorted
into secretory vesicles destined for
extracellular space, plasma membrane,
or other organelles
o Secretory granules are liberated by
exocytosis

By: Sachi Estreller |Section B

UST FACULTY OF MEDICINE AND SURGERY

Class of 2016
o

Cell Transport
Passive Diffusion

Dependent on presence of concentration

gradient

Lipids and lipid-soluble molecules

In general, plasma membrane is impermeable to

hydrophilic molecules; however, water, urea,
and bicarbonate are able to pass through passive
diffusion
Facilitated Diffusion

Concentration-dependent, requires presence of

protein carriers

Example: Aquaporins
o Allow water molecules to pass through
similar to passive diffusion
Active Transport

Operates against concentration gradient

ATP is required
Bulk Transport

Mediated by subcellular, transient structures

known as coated vesicles

Transport proteins embedded in the membrane

of a vesicle or soluble cargo within the lumen of
the vesicle

Dependent on the fluidity and deformability of

lipid membranes and mobility of intrinsic
membrane proteins

Formation of a coat vesicle:

o Coat proteins bind to membrane and
induce it to form a bud that is pinched
off
o Formed vesicle sheds coat proteins
and is moved by cytoskeleton to target
site

Exocytosis
o Secretory granules dock with plasma
membrane at the cell apex forming a
transient opening called a porosome
o Secretory product exits through the
porosome
o Secretory vesicle is recycled
o Regulated secretion

Dependent on signal
o Constitutive secretion

Continuous exocytosis

Receptor-mediated Endocytosis
o Important in uptake of ligands that
bind to surface receptors
o Receptors: intrinsic membrane
proteins with extracellular and
cytoplasmic domains

Process:

Cytoplasmic tail of receptor

binds to clathrin coat protein
in a coated pit

Receptors with ligands are

concentrated in the coated
pit

The pit buds off and forms

coated vesicle

Vesicles lose clathrin coat

and fuse with sorting
endosomes

Sorting endosomes
dissociate receptor and
ligand (d/t acid PH)

Membrane and receptors are

shuttled to recycling
endosomes

Sorting endosome containing

the ligand converts into a
late endosome called a
multivesicular body

Multivesicular body moved

to golgi to fuse with
lysosomes
Phagocytosis
o Cells of the defense system ingest and
kill pathogenic organisms
o Process:

Bacterium binds to cell

receptors

Formation of pseudopodia
that extend around
bacterium

Enveloping pseudopodia
form a phagosome

Phagosome fuses with

lysosome phagolysosome

Bacterium is broken down by

lysosome enzymes

Dead bacteria may be

released and maintained in
cytoplasm as residual body,
or expelled from cell

Transmembrane Signalling

Signalling molecules bind and activate

membrane receptors (usually enzymes)

By: Sachi Estreller |Section B

UST FACULTY OF MEDICINE AND SURGERY

Class of 2016
Mitochondria and Energy Production
Mitochondria

Elongated, cigar-shaped organelles

Very mobile, moves through microtubules

Localize at sites of maximum energy

requirement

Contains DNA and ribosomes resembling

chromosomes and ribosomes of bacteria

Undergo self-replication and synthesize some of

their own constituent proteins

Aerobic respiration takes place in the matrix and

inner membrane

Marker: succinate dehydrogenase

Four compartments:
o Outer membrane

Contains porin which allows

passage of small molecules

Contains enzymes that

convert lipid substrates into
forms that can be
metabolized within
mitochondrion
o Inner membrane

Forms the cristae

o Mitochondrial Matrix

Contains dense matrix

granules that are binding
sites for calcium

Site of Krebs Cycle, protein

and lipid synthesis
o Intramembranous Space

Contains a variety of
enzymes
Energy Production and Storage

Cellular respiration: supplies energy stored in the

form of ATP

Main substrates are simple sugars and lipids

Glycolysis
o Begins in the cytosol where it is
degraded to form pyruvic acid
o Pyruvic acid diffuses into mitochondria
where it is degraded to CO2 and H2O

Fatty Acid
o Pass directly to mitochondria

Lysosomes

Membrane-bound organelles containing

amorphous granular material
Lysosomal enzymes: proteases, lipases,
nucleases, collectively known as acid hydrolases
that are optimally active at PH 5
Involved in degradation of bacteria
(heterophagy) and cellular organelles
(autophagy)

Peroxisomes/ Microbodies

Small, spherical, similar to lysosomes but contain

different material
Contain oxidases involved catabolic pathways
which result in formation of hydrogen peroxide
Contain catalase that regulates hydrogen
peroxide concentration
Nucleoid: central crystalloid structure that
contains urate oxidase (not present in humans)

Annulate Lamellae

Visible in Electron Microscopy

Parallel arrays of cisternae with small pores at
regular intervals along length
Presence of diaphragms closing the pores
Functional significance not known

Cytoplasmic Inclusions
Pigments

Lipofuscin
o Represents an insoluble degradation
product of organelle turnover
o Wear and Tear or age pigment
o Residual bodies (remnants of
undigested molecules) may appear as
brown lipofuscin granules

Melanin
o Responsible for skin color
Lipids

Precursor molecules: FAs, triglycerides, and

cholesterol
Lipid droplets in the cell do not have limiting
membranes
Functions:
o Maintain constant turn-over of cell
membranes
o Store excess energy

Glycogen

Present in large amounts in liver cells

Glycogen granules are either:

o Beta Particles: irregular single granules
o Alpha Particles: glycogen rosettes
Others

Crystals
Secretory granules
Vacuoles

By: Sachi Estreller |Section B

UST FACULTY OF MEDICINE AND SURGERY

Class of 2016
Cytoskeleton

Functions:
o Maintains the shape and polarity of
the cell
o Movement
o Contractility
o Reorganization of constituents in cell
division
Microfilaments

Extremely fine strands of actin <8nm

Consist of two strings of bead-like subunits

twisted together like a rope

Stabilized by calcium ions and associated with

ATP molecules to provide energy for contraction

Functions:
o Found in microvilli
o Together with filamin, forms the cell
cortex which protects the cell against
deformation
o Cell movement, pinocytosis, and
phagocytosis
o Contractile properties

Centrosome

Made up of a pair of centrioles (called

diplosome) and centrosome matrix/
pericentriolar material

Self-duplicating

Centrioles: microtubule organizing center; nine

triplets of microtubules

Aster: microtubules radiate outwards from the

centrioles in a star-like arrangement

Delta Tubulin Ring Complexes: nucleus for

polymerization of microtubules

Tonofilaments/ Intermediate Filaments

8-12 nm diameter

Purely structural function; not known to be

contractile

Examples:
o Cytokeratin: in epithelial supporting
network
o Vimentin: in cells of mesodermal origin
o Desmin: muscle cells
o Glial fibrillary acidic protein: glial cells
o Lamin: form layer in inner side of
nuclear membrane
Microtubules

Appear as a circle composed of 13 globular

subunits

Provide for alterations in cell shape and position

of organelles; element of spindle apparatus

Originate from centriole found in centrosome

Microtubule associated proteins: stabilize

tubular structure
o Capping Proteins

Stabilize growing ends of the

tubules
o Motor Proteins

Dynein

Kinesin

By: Sachi Estreller |Section B

UST FACULTY OF MEDICINE AND SURGERY

Class of 2016
CELL CYCLE AND REPLICATION

Cell cycle: interval between mitotic divisions

S, G, M phases of the cell cycle are relatively
constant in duration; G1 phase is highly variable

Terminologies
Stem Cells

Labile cell

Relatively undifferentiated

Able to replace terminally differentiated cells

Terminally Differentiated Cells

Lost ability to undergo mitosis

Permanent cells arrested at G0 phase

Facultative Dividers

Do not normally divide but retain capacity to

undergo mitosis when the need arises

Arrested at G2 phase
Hypertrophy

Increase in bulk without multiplication of parts

Process in terminally differentiated cells

Examples: muscular hypertrophy, ventricular

hypertrophy
Hyperplasia

Abnormal or unusual increase in cell number

Process in cells that retain capacity for mitosis

Common pre-neoplastic response to stimulus

Examples: endometrial hyperplasia, gingival

hyperplasia, adrenal hyperplasia, benign
prostatic hyperplasia
Atrophy

Decrease in size or wasting away of a tissue or

body part

May happen in arrested development or

progressive decline of cellular processes

Examples: atrophy of the thymus, muscleatrophy

Metaplasia

Transformation of one tissue to another or one

differentiated type of cell to another
differentiated type

Occurs for the body to be able to adapt better to

changing conditions

Usually reversible; when stimulus or

environmental condition that induced
metaplasia is removed

Example: barretts esophagus

Interphase
G1 Phase

Between end of M phase and beginning of S

phase

Cells differentiate and perform specialized

functions

Usually the longest

S Phase

Synthesis phase when nuclear DNA is replicated

Completed before onset of mitosis

G2 Phase

Between end of S phase and beginning of M

phase

Cells prepare for mitotic division

Prolonged phase in facultative dividers

G0 Phase

State of continuous differentiated function

State of terminally differentiated cells; may last

for entire lifespan

Mitosis

Results in formation of two daughter cell

(diploid, genetically identical)
No duplication

Chromosomes

In humans, there are 46 chromosomes, paired in

22 homologous pairs called autosomes and 2 sex
chromosomes

Chromatids: identical chromosomes resulting

from S phase

Karyotyping: examination of chromosomes of

dividing cells

DNA
o Consist of a backbone containing
alternating deoxyribose and phosphate
moieties
o Deoxyribose: bound to a purine or
pyrimidine base; linked to a
complementary base on the other
strand
o Bases: adenine, cytosine, thymine,
guanine
o Genetic code: dependent on sequence
of bases

Bases are read in groups of

three called codons; each
codon codes for an AA

By: Sachi Estreller |Section B

UST FACULTY OF MEDICINE AND SURGERY

Class of 2016
Mitotic Apparatus

Comprises a spindle of longitudinally arranged

microtubules extending between a pair of
centrioles at each pole of the dividing cell

Visible only during the M phase; disaggregates

after mitosis is completed
Phases of Mitosis

Prophase
o Start: chromosomes first become
visible in nucleus
o Chromosomes become increasingly
condensed and shortened
o Nucleoli disappear
o Pairs of centriole migrate towards
opposite poles of the cell while the
spindle of microtubules is formed
o End: dissolution of nuclear envelope

Metaphase
o Mitotic spindle moves to nuclear area
and duplicated chromosomes attached
at the kinetochore to another group of
microtubules in the spindle
o Kinetochore

DNA and protein structure

on the chromosome located
at the centromere that binds
the duplicated chromosomes
(chromatids) together

Metaphase checkpoint:
kinetochore controls entry of
cell into the anaphase;
mitosis does not proceed
unless all chromatids are
aligned at the cell equator
o Chromosomes are arranged in the
metaphase plate

Anaphase
o Start: splitting of centromere
o Mitotic spindle lengthens
o Centrioles pulled apart and chromatids
are drawn to opposite ends of the
spindle

Telophase
o Chromosomes uncoil and regain
interphase conformation
o Nuclear envelope reforms and nucleoli
become visible
o Cytokinesis: plane of division defined
by position of spindle equator,
formation of cleavage furrow

Meiosis

Produces gametes that contains haploid number

of chromosomes
Involves one reduplication of chromosomes
followed by two cell divisions
Process
o Duplication of chromosomes
o Chiasma formation: crossing over of
chromatids that provides genetic
variability
o First meiotic division: separation of
pairs of chromatids still joined at
centromere
o Second meiotic division: splitting of
chromatids by pulling apart
centromeres
In males: four gametes are produced and mature
into spermatozoon
In females: one large gamete matures into
ovum, while the other three gametes
degenerate and form polar bodies

Apoptosis

Highly controlled and ordered mechanism by

which cells are removed in a way that causes
minimal disruption in surrounding tissue
Active process that requires energy; may be
normal or pathologic
Different from necrosis, which is associated with
pathology and is characterized by the inability of
cells to produce ATP and maintain homeostasis
Process:
o Extracellular signal molecule binds to
Fas, the death receptor; OR
o Intracellular signals such as DNA
damage cytochrome C release from
mitochondria into cytoplasm triggers
the event
o Caspase cascade is activated: enzymes
cleave cellular proteins

Pyknosis: condensation of
nuclear chromatin

Cell shrinks away from

neighboring cells

Karryorhexis: nuclear
material is fragmented,
dissolution of nuclear
membrane

Karyolysis: entire cell breaks

up
Apoptotic Body: fragments that contain nuclear
material; phagocytosed by macrophages or
neighbouring cells

By: Sachi Estreller |Section B

UST FACULTY OF MEDICINE AND SURGERY

Class of 2016
EPITHELIAL TISSUE

Derived from ectoderm, mesoderm, and

endoderm
Endothelium in vessels and mesothelium in
cavity linings are derived from mesoderm and
were not originally classified as epithelium
Functions
o Cover or line body surfaces
o Selective diffusion
o Absorption or secretion
o Physical protection and containment
Majority contain the intermediate filament,
cytokeratin
Critically dependent on diffusion of oxygen and
metabolites from supporting tissue because
basement membrane is not penetrated by blood
vessels

Classification of Epithelia

Traditionally classified according to

morphological characteristics:
o Number of cell layers
o Shape of component cells
o Surface specializations

Simple Epithelia

Single layer of cells

Functions in selective diffusion, absorption, and

secretion

Simple Squamous Epithelium

o Flattened, irregularly shaped
o Sometimes termed as pavemented
epithelium
o Found in lining surfaces involved in
diffusion of gases or fluids (eg. vessels
and cavity linings)

Simple Cuboidal Epithelium

o Square, but polygonal in surface view
o Nucleus usually round and centrally
located
o Found in small ducts or tubules (eg.
renal tubules)

Simple Columnar Epithelium

o Taller and columnar cells
o Nuclei are elongated and may be
located towards base, center, or apex
(polarity)
o Found in lining of absorptive surfaces
in the small intestine or secretory
surfaces in the stomach (eg.
gallbladder)

Simple Columnar Ciliated Epithelium

o Found mainly in female reproductive
tract
o Have surface specializations called cilia
(discussed later)

Pseudostratified Columnar Epithelium

o Single layer of cells that conveys the
erroneous impression that there is
more than 1 layer
o All cells rest on basement membrane
but nuclei are disposed at different
polarities
o Found in the airways of the respiratory
system
o Different from TRUE stratified epithelia
in two aspects:

Pseudostratified cells exhibit

polarity of nuclei, mainly
confined in basal 2/3 of
epithelium

Cilia never present in true

stratified epithelia

Stratified Epithelia

has two or more layers of cells

Functions mainly for protection

Stratified Squamous Epithelium

o Found in uterine cervix and epidermis
of the skin

Basal layer: cuboidal

Intermediate layer:
polygonal

Surface layer: flattened

o Withstand abrasion but not
desiccation

Stratified Cuboidal Epithelium

o Thin, stratified layers (2-3) of cuboidal
cells
o Found in lining of the larger excretory
ducts of the exocrine glands

Transitional Epithelium
o Found only in urinary tract

Basal layer: cuboidal

Intermediate layer:
polygonal

Surface layer: umbrella cells

that may contain 2 nuclei

In the stretched state,

intermediate and surface
layers are flattened
o Accommodate stretch and withstand
toxicity of urine

Neuroepithelium
o Chief cell surrounded by supporting
cells made up of columnar and basal
cells

By: Sachi Estreller |Section B

UST FACULTY OF MEDICINE AND SURGERY

Class of 2016

Glandular Epithelia

Invaginations of epithelial cell surfaces

Exocrine
o Connected to a surface epithelium by a
branching system of ducts

Endocrine
o Lost connection to epithelial surface
and release secretions directly into
blood

Membrane Specializations

Intercellular surface specializations function to

form a continuous cohesive layer of epithelia
and also for cell communication
Luminal surface specializations function for
secretion, absorption, and mobilization
Basal surface specializations provide anchorage
and structural support

Intercellular Junctions

Junctional Complex
o Composed of tight junction, zonula
adherens, and desmosomes

Zonula Occludens
o Also called tight junctions
o Forms a continuous circumferential
band that:

Block passage of molecules

Separate apical and

basolateral plasma
membrane compartments
o Sealing strands stitch membranes
together, with each strand comprising
of two molecules of claudin on the
plasma membrane and actin on the
cytoplasm
o Fascia Ocludens: structurally similar
but discontinuous strips of tight
junctions that are found in blood
vessels

Zonula Adherens
o Form a contractile circumferential
band
o Transmembrane protein: cadherin
o Anchoring proteins: catenin, vinculin,
alpha actinin)
o Bind to actin molecules

Macula Adherens
o Also called desmosomes
o Transmembrane protein: cadherin
o Anchoring protein: desmoplakin,
plakoglobin)
o Bind to intermediate filaments

Gap Junctions
o Conduit for passage of small molecules
between adjacent cells; large
molecules and negative ions are
denied passage
o Important in the control of growth,
development, cell recognition, and
differentiation
o Contains transmembrane channels
called connexons, made up of 6
connexin proteins

Hemidesmosomes

Variant of desmosomes that bind intermediate

filaments linking the basement of the cell to the
basement membrane

Transmembrane protein: integrins

Anchoring protein: plectin

Bind to intermediate filament

Extracellular binding site: laminins in BM

Cilia

Beat in wave-like synchronous pattern

Function in propelling mucus or fluid in a
consistent direction over the epithelial surface
Axoneme: central core consisting of 20
microtubules arranged as a central pair
surrounded by 9 peripheral doublets
Basal Body: nine microtubule triplets continuous
with the base of the cilium
Dynein: ATPase that fuels ciliary movement

Microvilli

Minute finger-like projections on luminal plasma

membrane

Termed as brush borders in light microscopy

Core contains actin microfilaments which insert

into the terminal web anchored to the zonula
adherens
Stereocilia

Extremely long microvilli found in the male

reproductive tract

Facilitate absorptive processes

Goblet Cell

Modified columnar epithelial cells that

synthesize and secrete mucus

Contains aggregation of mucigen granules which

are released through exocytosis and combines
with water to form mucus

Mucigen: mix of acidic and neutral proteoglycans

RER and Golgi apparatus are prominent

By: Sachi Estreller |Section B

UST FACULTY OF MEDICINE AND SURGERY

Class of 2016
Keratin

Occurs in Stratified Squamous Epithelium

During maturation, cells accumulate cross-linked
cytokeratin resulting in the formation of a tough,
non-living surface layer of squames consisting of
a protein called keratin
In the keratin layer nuclei become pyknotic then
disappear

Exocrine Glands
Classification by Means of Secretion

Merocrine (Eccrine)
o Most common form of secretion
through exocytosis

Apocrine
o Discharge of free, unbroken,
membrane-bound vesicles
o In lipid secreting glands in the breasts
and some sweat glands

Holocrine
o Discharge of whole secretory cells with
subsequent disintegration of cells to
release the product
o In sebaceous glands
Morphological Classification

Simple Tubular
o Single, straight, tubular
o In large intestine

Simple Coiled Tubular

o Single, coiled in 3D
o In sweat glands

Simple Branched Tubular

o Several tubulosecretory portions that
converge in a single unbranched duct
o In the stomach

Compound Branched Tubular

o In the duodenum

Simple Acinar
o Rounded exocrine secretory unit
o In penile urethra

Simple Branched Acinar

o Several secretory acini empyting into a
single excretory duct
o In sebaceous glands

Compound Acinar
o Acinar secretory units draining into a
branched duct system
o In pancreas

Compound Tubuloacinar
o Branched tubular, branched acinar,
and branched tubular with acinar end
pieces called demilunes
o In submandibular gland

2 types of secretory cells

Mucous
o Tubular
o Acidophilic
o Striated granular
o With canaliculi
o Bounded nucleus and narrow lumen

Serous:
o Acinar and demilunes
o Basophilic
o Reticulated
o No canaliculi
o Flattened nucleus, wide lumen

Endocrine Glands

Consist of clusters or cords of secretory cells

surrounded by a rich network of blood vessels
Most release more than one hormone
Some consist of more than one type of secretory
cell
Hormone secretion is controlled by metabolic
factors, the nervous system, and other
hormones

Follicular Endocrine Gland

Seen in thyroid gland

Stores hormone in spherical cavities enclosed by

secretory cells

By: Sachi Estreller |Section B

10

UST FACULTY OF MEDICINE AND SURGERY

Class of 2016
CONNECTIVE TISSUE

Mesodermal in origin
o Mesencymal cells are stellate or
spindle-shaped with cytoplasmic
extensions; differentiate into all cell
types found in mature supporting
tissue
Functions
o Structural and metabolic support
o Exchange of nutrients and metabolites
o Protection and tissue repair
o Insulation
o Hematopoietic and immunologic

Connective Tissue Cells

Fibroblast

Secrete ECM in most tissues

Dominant RER and Golgi Apparatus reflecting

dominant protein-secreting function

Maintain integrity of supporting tissues by

continuous slow turnover of ECM constituents
Chondrocytes and Osteocytes

Secrete ECM in cartilage and bone

Myofibrolasts

Have additional contractile properties

Adipocytes

Storage of metabolism and fat

Defense Cells of Supporting Tissue

May be fixed (macrophages and mast cells) or

wandering (leukocytes)

Reticuloendothelial system
o Refers to phagocytic cell network
located in the marrow, spleen, lymph
node, and liver that have a supporting
framework of reticular fibers

Mast Cells
o Found in skin, GI lining, blood vessels,
and lining of peritoneal cavity.
o Similar to basophils with some
differentiating properties:

Less condensed chromatin

More uniform distribution of

processes

> cytoplasmic filaments and

granules

Lack of glycogen granules

o Mast cell degranulation results in the
release of histamine and other
vasoactive mediators which induce
immediate hypersensitivity and
anaphylactic shock

Macrophages
o Active cells exhibit irregular
cytoplasmic projections or
pseudopodia which are involved in
amoeboid movement and
phagocytosis
o Functions:

Tissue scavengers

Antigen presenting cells

during opsonisation

Cytokine secretion that

enhances immune response

Lymphokines: increase the

metabolic and phagocytic
activity of macrophages

Connective Tissue Fibers

Collagen Fibers

Most abundant protein in the body

Most notable function is tensile strength

Secreted in the form of tropocollagen that

polymerize in the ECM to form collagen

Types:
o Type I: in fibrous supporting tissue,
dermis of the skin, tendons, ligaments,
and bone
o Type II: hyaline cartilage
o Type III: reticulin, found in highly
cellular tisues

also called argyrophillic

fibers because it is stained
through silver impregnation
o Type IV: basement membrane
o Type VII: anchoring fibrils for basement
membrane
Elastin Fibers

Has stretch and elasticity

Secreted in the form of tropoelastin

Deposition of elastin as fibers requires that

presence of fibrillin (structural glycoprotein)

Found in lungs, skin, urinary bladder, and blood

vessels

Ground Substance

Consist of GAGs or mucopolysacharrides

GAG: double sugar units usually uronic acid and
amino acid sugar (N-acetylglucosamin and Nacetylgalactosamine)
Hyaluronic Acid: predominant GAG, without
sulphate side groups
Other GAGs: chondroitin-4 and 6- sulphate,
dermatan sulphate, heparin and heparin
sulphate, and keratin sulphate
GAGs are hydrophilic ECF confers turgor

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Structural Glycoproteins

Fibrillin

Loose Areolar Connective Tissue

Few collagen fibers present

Found in lamina propria, superficial and deep

fascia

Enhance adhesion between other extracellular

constituents and deposition of fibers in elastin

Dense Regular Connective Tissue

Compact collagen fibers oriented

unidirectionally

Found in tendons, ligaments, and aponeurosis

Fibronectin

Control deposition and orientation of collagen in

ECM

Enhance binding of cell to extracellular material

Laminin

Form links between cell membranes and

basement membrane
Entactin

Bind laminin to Type IV collagen in basement

membrane
Tenascin

Binds to integrins and play a role in embryonic

nerve cell growth

Basement Membrane

Adult Connective Tissue

Fibrillary: fibrillin, fibronectin

Non-Fibrillary: laminin, entactin, tenascin
Function as links between cells and ECM

Sheet-like arrangements of ECM that act as

interface between support tissues and
parenchymal cells
Main constituents: heparin sulphate, collagen
type IV, fibronectin, laminin, and entactin
Functions:
o Metabolic support
o Control of epithelial growth and
differentiation
o Regulation of permeability
Layers:
o Lamina Lucida

Electron lucent

Mainly type IV collagen

bound to basal plasma
membrane by laminin

Entactin mediates binding of

laminin to collagen
o Lamina Densa

Electron dense, intermediate

layer
o Lamina Fibroreticularis

Merges with underlying

supporting tissue

Mainly type III collagen

bound to integrin of
parenchymal basal
membrane by fibronectin

Dense Irregular Connective Tissue

Compact collagen fibers oriented

multidirectionally

Found in GIT, dermis, periosteum,

perichondrium
Elastic Connective Tissue

Contain elastin fibers, slender and refractile

Found in wall of hollow organs, blood vessels,

trachea, bronchi, yellow ligaments, suspensory
ligaments
Reticular Connective Tissue

Contains reticulin fibers

Supporting framework of hematopoietic and

lymphoid organs
Adipose Connective Tissue

Adipocytes
o Adapted for storage of fat in lipid
droplets
o Derived from mesenchymal cells that
develop as lipoblasts
o Signet-ring appearance with the
nucleus at the periphery
o Secrete adipocytokines that modulate
energy metabolism
o Generally has a rich blood supply
o Have receptors for insulin,
glucocorticoids, growth hormone and
noradrenaline

Stored fat from:

o Triglycerides from liver
o Circulating dietary fat
o Triglycerides from glucose within
adipocytes

Types:
o White Adipose Tissue

Unilocular

Energy store, thermal

insulator, and cushion
o Brown Adipose Tissue

Multilocular

Found in newborns and

hibernating mammals

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Function in body
temperature regulation: nonshivering thermogenesis
induced by cold stress
Contains thermogenin which
uncouples mitochondrial
metabolism from production
of ATP to produce heat
Cytochrome accounts for the
brown color of adipocytes

Embryonic Connective Tissue

Mesencymal Connective Tissue

With capacity for differentiation

Mucuous Connective Tissue

Formed by primitive fibroblasts (spindleshaped/stellate)

Whartons jelly of umbilical cord

Specialized Connective Tissue

Cartilage, bone, and blood to be discussed in a

later section

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SKELETAL TISSUES

Mesodermal in origin
Rigid form of connective tissue due to
calcification of ground substance
Inorganic elements: Mg, Ca, Na
Organic elements: calcified matrix
Functions:
o Internal support
o Attachment of muscles and tendons
o Contains bone marrow
o Protect vital organs
o Calcium storage

Cartilage

provides smooth articular surface and structural

support; also important in bone formation
made up to extracellular matrix: ground
substance + fibers
Ground Substance
o Made up of proteoglycans
o Accound for solid and flexible
properties of cartilage
o Sulphated GAGs predominate such as
chondrotin and keratin sulfate
Most are avascular thus exchange of metabolites
between chondrocytes and surrounding tissue
depends on diffusion through water solvation of
ground substance

Cartilage Formation

Primitive mesenchymal cells differentiate to

chondroblasts which synthesize ground
substance and fiber

Chondroblasts
o Separated by cartilaginous matrix and
undergo mitotic division in separate
areas, maturing into chondrocytes

Chondrocytes
o Maintain the integrity of the cartilage
matrix
o Arranged in clusters of 2-4 enclosed by
amorphous cartilage matrix
o Involved in synthesis of ground
substance and fibers of the ECM
o Have prominent RER and Golgi
Apparatus

Appositional Growth
o Through the perichondrium, a layer
surrounding mature cartilage
composed of fibers and spindle-shaped
cells
o Cells transform into chondroblasts and
produce new cartilage

Interstitiial Growth
o Occurs through further division of
chondrocytes trapped within mature
cartilage
o Mature cartilage has little capacity to
repair and regenerate due to poor
vascular supply

Hyaline Cartilage

Most common type

Found in nasal septum, larynx, tracheal rings,

articular surfaces

Precursor in the developing bone

Consists of collagen type II (except articular

cartilage)
Elastic Cartilage

Found in external ear, epiglottis, laryngeal

cartilage, and walls of Eustachian tube

Elasticity is derived from elastic fibers in the

cartilage matrix
Fibrocartilage

Found in intervertebral discs, articular cartilage,

and pubic symphysis, joint capsules, ligaments,
and tendons

Chondrocytes typically arranged in rows

between dense collagen layers

Bone

Provides a rigid protective and supporting

framework
Also serves as a calcium reservoir
Composed of cells and type I collagen called
osteoid, mineralized by deposition of calcium
hydroxypatite

Cells of the Bone

Osteoprogenitor
o Primitive mesenchymal cell line where
osteoblasts and osteoclasts originate

Osteoblasts
o Synthesize osteoid and mediate its
mineralization; lined up in bone
surfaces
o Inactive: spindle shaped; active:
cuboidal

Osteocytes
o Inactive osteoblasts embedded in
formed bone; assist in nutrition

Osteoclast
o Phagocytic, multi-nucleated cells that
erode bone for turnover and
refashioning; come from monocytemacrophage cell line

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o
o

Found in Howships lacunae,

depressions of resorbed bone
With a ruffled border formed by
microvilli that secrete organic acids
and proteolytic enzymes

Types of Bone According to Collagen Organization

Woven Bone
o Collagen fibers arranged randomly and
irregularly
o Fabricated during periods of rapid
bone growth: embryogenesis, reactive,
neoplastic
o Hypercellular with large osteocytes
and lacunae distributed in haphazard
fashion
o Prone to greenstick fracture
o Pleomorphic osteocytes

Lamellar Bone
o Collagen fibers arranged in parallel
o Synthesized more slowly; stronger
o Less cellular, small osteocytes and
lacunae
o Uniform osteocyte morphology
o May be compact or spongy
Compact Bone (Substantia Compacta)

Parallel columns made up of concentric bone

layers surrounding the haversian canal

Haversian System
o Haversian channel

Contains lymphatics, blood

vessels, nerves
o Volkmanns Canal

Connect neurovascular
bundles in haversian canals
with andosteum and
periosteum
o Lacunae

Containing ostecytes and are

seen in between lamella
o Canaliculi

Minute interconnecting
canals in between lacunae
containing cytoplasmic
extensions of osteocytes

Provide passage for

circulation of ECF and
diffusion of metabolites
between lacunae and vessels
of haversian canals

Concentric Lamella

Internal/Endosteal Lamella

External/Periosteal Lamella

Interstitial Lamella: remnants

of resorbed lamellae no
longer surrounding haversian
canals
Periosteum

Bound to underlying bone by

Sharpeys Fibers

Layer of condensed fibrous

tissue containing osteogenic
cells

Spongy Bone (Substantia Spongiosa)

Irregular branching bony spicules forming a

network of interconnecting spaces

With thin trabeculae made up of irregular

lamellae

Trabeculae is lined by thin endosteum containing

flat inactive osteoblasts

Number, thickness, and orientation are

dependent on the stresses to which the bone is
exposed

Contains red (hematopoietic) and yellow

(adipose) marrow

No haversian system
Types of Bone According to Structure

Long Bone
o Diaphysis

Mostly compact bone

o Epiphysis

Mostly spongy bone

o Epiphyseal Plate

In between epiphysis and

diaphysis
o Metaphysis

Transition connecting
epiphyseal plate and
diaphysis
o Periosteum and Endosteum

Lining of outside and inside

of bone

Flat Bone
o Made up of 2 layers of compact bone
(inner and outer tables) surrounding
spongy bone layer (diploe)

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Joints
Synovial Joint

Allows extensive movement

Also known as diarthroses

Articular cartilage
o Hyaline cartilage that covers articular
surfaces
o Infers resistance to compressive forces

Synovium
o Secretory cell layer that secretes
synovial fluid in the cavity to facilitate
smooth articulation
o May be fibrous (dense), areolar
(loose), or adipose (fat) synovium
o Synovial fluid contains:

Hyaluronic acid and

associated glycoproteins
from Type B Synoviocytes

Transudate from capillaries

Leucocytes and monocytes

o Type A Synoviocytes

With extensive golgi complex

and lysosomes
o Type B Synoviocytes

With extensive endoplasmic

reticulum

Cruciate ligaments
o Internal ligaments that limit joint
movement together with fibrous joint
capsule and external fibro-elastic
ligaments
Non-Synovial Joints

Have limited movement

No free articular surface, instead joined by dense

collagenous tissue

Types:
o Dense fibrous Tissue

Called syndesmoses that

transform to synostoses
when replaced by bone

Found in sutures of the skull

o Hyaline Cartilage

Called synchondrosis

Found in union of first rib

with sternum
o Fibrocartilage

Called symphyses

Found in pubic symphysis

and intervertebral discs

Tendon

Tough flexible straps that connect muscles to

bone
Composed of compact linear collagen fibers with
nuclei of inactive fibroblasts
Poorly vascularised and heals slowly
Anchor to muscle through myotendinous
junctions
Anchor to bone through the periosteum or
Sharpeys Fibers

Bone Development and Growth

Bone Matrix and Mineralization

70% inorganic salts

o Mainly calcium and phosphate in the
form of hydroxypatite crystals
o Magnesium carbonate
o Sodium
o Potassium

30% organic
o Type I collagen creates hole zones, the
initial site for mineralization
o Ground substance proteoglycans
consist of hyaluronic acid and
chondroitin sulphate
o Osteocalcin: involved in binding
calcium during mineralization
o Osteonectin: bridging function
between collagen and mineral
component
o Sialoprotein

Process
o Collagen and other organic
components synthesized from RER of
osteoblasts Golgi Apparatus
secreted as osteoids
o After maturation phase, calcium
phosphate salts precipitate in the hole
zones
o Pyrophosphate: inhibitor that controls
bone mineralization
o Alkaline Phosphatase: neutralize effect
of pyrophosphate
Intramembranous Ossification

Skull vault, maxilla, mandible

Occurs within membranes of condensed,

primitive mesenchymal tissue

Process:
o Mesenchymal cells differentiate into
osteoblasts that begin synthesis of
osteoid at centers of ossification
o Mineralization of osteoid
o Osteoblasts trapped in lacunae evolve
into osteocytes and cytoplasmic
extensions shrink and form canaliculi

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o
o
o

Osteoprogenitor cells continue to form

osteoblasts
Fusion of adjacent ossification centers
occurs
Woven bone is remodelled by
osteoclastic activity and subsequent
osteoblastic deposition of mature
compact bone

Endochondral Ossification

Long bones, vertebrae, pelvis, skull base

Permits functional stress to be sustained during

skeletal growth

Process of Primary Ossification

o Zone of Reserve Cartilage

Cartilage model is first

formed in hyaline cartilage
o Zone of Proliferation

Appositional growth occurs

to form the different parts of
bone
o Zone of Maturation

Chondrocytes within the

model enlarge and resorb
the cartilage so as to leave
perforated trabeculae of
cartilage matrix
o Zone of Hypertrophy and Calcification

Cartilage matrix is ossified

o Zone of Cartilage Degeneration

Chondrocytes degenerate,
primitive mesenchymal cells
and blood vessels invade the
spaces occupied by
chondrocytes and
differentiate into osteoblasts
and hematopoietic cells
o Osteogenic Zone

Osteoblasts begin to form

woven bone
o Perichondrium develops osteogenic
potential and assumes the role of
periosteum
o Periosteum lays down a thin layer of
bone on the surface
o Results in bony diaphysial shaft with
cartilaginous epiphyses at each end

Process of Secondary Ossification

o Conversion of central epiphyseal
cartilage into bone

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