HUMAN ANATOMY

EVALS 3
Lecture 2: Connective Tissue
Lecturer: Eduardo G. Gonzales, M.D.
Composition:
INTRODUCTION 1. cells
 Characteristics: extracellular material is abundant; cells 2. extracellular substance (extracellular matrix)
are relatively sparse a. ground substance
 Origin: almost entirely derived from mesoderm (some Characteristics:
CT in the head is derived from ectoderm)  amorphous
 Classification:  transparent
1. Connective tissue proper  homogenous
Composition:  hydrated gel
a. cells Composition:
b. extracellular substance (extracellular matrix)  water
1. ground substance  proteoglycans
2. fibers  mineral salts
 glycoproteins
2.
Special types of Connective Tissue b. fibers
 Cartilage *Blood vessels and nerve fibers are abundant in the extracellular
 Bone substance
 Blood
 hemopoietic tissue (myeloid and lymphoid) GROUND SUBSTANCE
CONNECTIVE TISSUE PROPER 1. High water content makes it easier for oxygen,

Lecture Content/table of contents nutrients, and other needed materials to diffuse

[Link] Tissue Proper from blood to CT cells, and for waste products of
a. Ground Substance
b. Fibers metabolism to diffuse from the cells to blood.
[Link] fibers
2. Glycoproteins
2. Elastic fibers
3. Reticular fibers  Composition:
c. Cells o Fibrillin
[Link] cell  Fibrillary glycoprotein
[Link] and Fibrocyte  Too thin (10-12 nm) to be
3. Reticular cell
4. Mast cell considered connective tissue fiber
5. Macrophage  Component of elastic fibers
6. Plasma Cell  Non-sulfated molecule
7. Leukocytes or white blood cell
d. CT Proper Classification
 EM: made of electro-lucent core
[Link] CT
2. Special Types of CT Proper surrounded by and electron-dense
a. Adipose tissue area
b. Reticular Tissue o Fibronectin
c. Elastic Tissue o Laminin
d. Mucous Tissue
o Thrombospondin
Note: The last three are probably involved in cell adhesion and
Functions: migration.
2  Binds parts together while allowing for some degree of  At least two glycoproteins are fibrillary(in the form of
3 movement of these parts in relation to their immediate
4
microfibrils)
anatomical neighbors, as the name implies; found all 3. Proteglycans
5
over the body and can be regarded as a “glue”
 Macromolecules
 envelops muscles
 Main structural component of ground substance
 forms stroma (supporting framework) of some
 Vary in size and structure
organs
 Responsible for gelatinouscharacter of ground
 acts as an avenue for blood vessels and nerves
substance of CT
into and away from interiors of organs or
 Basic structure:
parts of the body
1. “core protein”
 allows exchange of gases and substances
2. attached glycosaminoglycans (GAGs)- disaccharides
between blood and other basic tissues
(carbohydrates; make ground substance acidic)-
 provides “arena” for defense cells to combat invading attached covalently in a radiating pattern to core
microorganisms protein

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 HUMAN ANATOMY
EVALS 3
Lecture 2: Connective Tissue
Lecturer: Eduardo G. Gonzales, M.D.

 Acidic nature of GAGs- due to presence of sulfate  in connective tissue proper secreted
and carboxyl group in their sugar components by fibroblasts and mesenchymal
 Common GAGs include: cells
i. Chondroitin sulfate  in cartilage and bone secreted by
ii. Keratin sulfates I and II chondroblasts and osteoblasts.
iii. Heparan sulfate (Note: matrix of cartilage and bone
iv. Dermatan sulfate also contain collagen fibers)
 Most proteoglycan aggregates (complexes) that o in extracellular matrix:
consist of: a. 3 procollagen molecules ( a chains) twist
1. Proteoglycan molecules around each other to form
2. Hyaluronic acid tropocollagen molecules (much like
o Most abundant type of GAGs in CT fibers of the rope and getting bound
o Only one without a sulfate- side group together by hydrogen bonds)
o Does not form covalent bond with core protein b. extra peptide groups of procollagen
o Serves as backbone to which proteoglycan molecules are removed enzymatically
molecules are attached by link proteins o tropocollagen molecules aggregate to form
3. Link protein- binds 1 and 2 microfibrils
o 45-100 nm diameter
EXTRACELLULAR FIBERS o microfibrils collect to form fibrils
 Primarily responsible for supportive function of CT (macrofibrils)
proper o fibrils are 0.3-0.5 mm
 Types: o in LM, hard to distinguish
1. Collagen fibers o in EM, have dense transverse
2. Elastic fibers bands set at 64 nm along length of
3. Reticules fiber fiber
 These three types of CT occur in varying combinations in o fibrils aggregate to form fibers
the CT that are present different parts of the body. o 2-10 mm
COLLAGEN FIBERS (COLLAGENOUS FIBERS) o in LM, easy to distinguish
 Ordinary Connective Tissue o EM: dense transverse bands that
are set at 64 nm intervals along their
 Present in all connective tissues, although in varying
length
amounts
o fibers collect to form bundles
 Main fiber in collagenous CT, the most abundant CT type
 Summary:
in the body
 Procollagen-> tropocollagen-> collagen microfibrils->
 Tensile strength is greater than steel
collagen fibrils-> collagen fibers->
 Flexible, but inelastic
collagen bundles
 Colorless individually
ELASTIC FIBERS
 White when abundant, as in tendons
 fine, highly refractile
 Collect into bundles that appear pink in H & E
 often branch (unlike collagen fibers); branches
preparations since they are acidophilic.
anastomose
 Masson’s trichrome: collagen fibers appear blue
 impart yellow color to fresh tissue
 Consists of Collagen
 in H&E: unstained; appear as refractile, pinkish-yellow
o most abundant protein in body
lines
o accounts for about 25% of body’s dry weight
 in LM
o family of structural proteins
o difficult to distinguish in H & E
 28 distinct types (I- XXVIII) differ by
o selectively stained blue to black by orcein;
amino acid composition
resorcin-fuschin aldehyde- fuschin, etc.
 sequence of alpha- chains
 less tensile strength than collagen, but very supple
o not all types form fibrils and fibers
o in connective tissue, practically all are  recoil back to their original length when stretching force
 types I, II, and III is released
 Collagen fibers are made up of collagen type I  abundant in structures subjected to frequent stretching
o ligamenta flava - between vertebrae
 Formation
o elastic cartilage – form framework of auricle
o Procollagen
and external acoustic meatus of ear, external
 precursor of collagen fibers
nose, auditory tube, epiglottis and some parts
 has polypeptide chains longer than
of larynx.
those in mature collagen

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 HUMAN ANATOMY
EVALS 3
Lecture 2: Connective Tissue
Lecturer: Eduardo G. Gonzales, M.D.

 In EM: fibers)
o amorphous core of elastin o reacts positively with PAS.
 highly-insoluble protein  Formation:
 responsible for elasticity of elastic o same as collagen fibers
fibers
 resistant to boiling and hydrolysis by o but, precursor secreted by specialized
acids, alkali, and most enzymes but fibroblasts called reticular cells
hydrolyzed by pancreatic enzyme CELLS
elastase 1. Resident cells- stay permanently in CT
 only one genetic type  mesenchymal cell
 exists in 2 forms:  fibroblast and fibrocyte
 fibrillar - in elastic fiber  adipose cell
(surrounded by microfibrils)  reticular cell
 nonfibrillar -comprises  mast cell
elastic lamellae of blood  resident macrophage
vessels. 2. Visiting cells- transient in CT
o Microfibrils (longitudinal branches)  inflammatory macrophage
 mostly fibrillin  plasma cell
 surround elastin.  leukocytes or white blood cell
 Elastogenesis/ Elastic fiber formation MESENCHYMAL CELL
 raw materials needed for formation of fibers  Multipotential cell that has differentiated from
1. microfibrils (mostly fibrillin) Pluripotental stem cell
2. tropoelastin – precursor of elastin  Capable of differentiating into several types of cells
 in connective tissue, raw materials secreted to  Stem cells of most connective tissue cells as well as
intercellular space by bone, cartilage, and muscle cells
1. fibroblasts  Pluripotental stem cell
2. mesenchymal cells o common origin of all cells of body
 in elastic lamellae, tropoelastin is secreted by smooth o rare in adults, but some exists, especially in
muscle cells bone marrow
 in intercellular space: o differentiate to multipotential stem cell
1. microfibrils form bundles while tropoelastin polymerizes
to form elastin
2. tropoelastin incorporated to outer aspect of microfibril
bundles (When fiber has enough elastin, additional
microfibril bundles are added on the external surface)
3. later, with addition of more microfibrils and elastin, the
latter gets to occupy core of fiber.
 Elastin that forms the elastic lamellae in arteries is
synthesized by smooth muscle cells that lay down
elastin in fenestrated sheets or lamellae arranged in
concentric layers between layers of smooth muscle  rare in adults; but some exist usually in the bone
marrow and in CT near capillaries
RETICULAR FIBERS  abound in the embryo and in the umbilical cord
 composed of type III collagen  in LM, difficult to distinguish from fibroblast
 compared to collagen fibers (type I collagen) o cytoplasmic processes
o finer (0.5-2mm)  makes cell stellate
o more sugar groups o nucleus
o branch and anastomose. (form extensive  oval
networks in some organs)  distinct nucleolus
 sparse in most connective tissue  fine chromatin
 main intercellular fiber in:  in EM, compared to fibroblast
1. reticular tissue o coarser chromatin
2. lamina fibroreticularis of basement membrane o fewer organelles
 in LM
o not distinguishable in H & E FIBROBLAST
o stain black with silver salts (argyrophilic  most abundant cell type in connective tissue

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 HUMAN ANATOMY
EVALS 3
Lecture 2: Connective Tissue
Lecturer: Eduardo G. Gonzales, M.D.

 originates in embryo from mesenchymal cells o fat droplet is removed during processing
 capable of mitosis, but divide infrequently leaving a large empty space (dissolved and
 long-lived and sturdy washed away by solvents like xylol during
 Routine histologic preparations: lie close to or adhere processing)
to collagen fibers o signet ring cell
 function: synthesis of  large empty space
o organic components of ground substance  nucleus on one side.
 proteins  Fat is fixed and stained black by osmium tetroxide and
 glycoproteins colored by dyes such as Sudan III.
 glycosaminoglycans  mature cells do not divide
o precursors of fibers (collagen, elastic and  new cells sourced from
reticular) o mesenchymal cells
 irregular cytoplasmic processes o pre-fat cells
 cytoplasm  cells in intermediate step between
o basophilic due to presence of well-developed stem cell and fat cell
rER  reside in adipose tissue
 nucleus  uncertain lineage (mesenchymal cell
o pale or fibroblasts?)
o ovoid  divides twice before becoming full-
o fine chromatin fledged fat cells
o visible nucleolus. RETICULAR CELL
 There is some functional specialization among  fibroblast that synthesizes only precursors of type III
fibroblasts. collagen
 Reticular cells- fibroblasts that synthesize reticular  present in small numbers in most connective tissue
fibers that do not synthesize collagen or elastic fibers  abundant in reticular tissue.
 in H & E
FIBROCYTE o slightly larger than fibroblast
 idle or resting fibroblast o nucleus
 can become active (in proper conditions such as  large
wound- healing)  pale staining
 compared to fibroblast o cytoplasmic processes
o smaller  long
o fewer processes  embrace reticular fibers.
o acidophilic cytoplasm MAST CELL
o nucleus is dark and compact.  mastocytes; histaminocytes
ADIPOSE CELL  large, ovate cell (15-20 mm)
 a.k.a., fat cell, adipocyte  not distinguishable in H & E
 specialized to store lipid in its cytoplasm (mainly  nucleus
triglyceride) o centrally located
 present in variable numbers in practically all connective o spherical
tissues  secretory granules in cytoplasm
 predominant cellular element in adipose tissue (a type o numerous
of connective tissue) o membrane bound
 fat in adipose cells is synthesized by cells from glucose o 0.3-0.8 mm in diameter
that is brought to the cells from the liver or obtained by o variable shape
the cell from ingested food, via bloodstream, in the form o metachromatic
of chylomicron o dark purple with toluidine blue; not seen in
 look like fibroblasts before accumulating fat or when fat H&E
contents has been depleted o contain histamine (dilates and makes blood
capillaries more permeable and which
 lipoblast- fat cell is only starting to accumulate fat and
stimulates the smooth muscle cells especially
only few small fat droplets in its cytoplasm can be seen
of the bronchioles in respiratory tract and
 mature cell possesses single large fat droplet
some proteases) and heparin (an
 fat droplet flattens and pushes nucleus and
anticoagulant).
cytoplasmic organelles to one side of the cell
 In EM: mast cells are seen to possess microvilli
 in H&E
 sparse in most connective tissues

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 HUMAN ANATOMY
EVALS 3
Lecture 2: Connective Tissue
Lecturer: Eduardo G. Gonzales, M.D.

 abundant in a. pulmonary alveolar macrophage (aleveoli of

o lamina propria of GI and respiratory tracts lungs)
o underneath skin b. Kupffer cell (sinusoids of liver)
o along course of small blood vessels c. histiocytes ( connective tissue).
 involved in immediate-type hypersensitivity reactions  in connective tissue, classified into (based on mobility):
(allergic reaction), anaphylaxis, wound healing and 1. fixed macrophages
defense against pathogens  attached to collagen fibers
 When activated: 2. free macrophages
1. degranulates and releases  ameboid
 heparin  wander around in extracellular matrix
 histamine  (note: fixed macrophage - can detach and
 proteases become motile; and conversely)
2. synthesizes and releases mediators of  in connective tissue, classified into:
inflammation not in granules 1. resident
 leukotriene  inhabits a given site
 prostaglandin  not as immunologically active as inflammatory
 cytokines macrophages
 Mast cell vs. Basophil  increase their number by differentitating from
a. both have cytoplasmic granules that contain monocytes or by mitosis (limited capacity due
histamine and heparin to local proliferation)
b. both arise from bone marrow, but from 2. inflammatory
different progenitor cells  migrates to a site in response to a stimulus
c. colony-forming unit--basophil (CFU-Bas) =  increase their number by differentiating from
progenitor cell of basophil monocyte.
d. CFU-Mast = progenitor cell of mast cell  activated macrophages
e. mast cells settle permanently in connective a. those with increased functional
tissue and do not circulate in blood activity (phagocytic and antigen-
f. basophils are smaller but more mobile processing) in response to certain
g. basophils have shorter life spans (few days); stimuli.
mast cells live for weeks to months b. deactivated by certain chemical
h. mast cells can divide; basophils cannot. substances produced by body.
i. nucleus is dark and compact. c. life span: about 2 months to 70 days
although mores recent evidence
MACROPHAGES suggest 6-16 days.
 differentiate from monocyte  assume a variety of forms based on their
 phagocytes that serve as effector cells of the location and state of activity
mononuclear phagocyte system, i.e., family of cell  in LM:
that includes: a. similar to fibroblast unless with
o stem, progenitor and precursor cells (in bone phagocytosed material (in CT)
marrow) b. fixed macrophage
o monocytes i. attached to collagen fiber
o macrophages ii. spindle-shaped
 functions: iii. oval nucleus
o heterophagy - ingests bacteria and iv. coarse chromatin
exogenous particulate materials c. free macrophage
o autophagy - ingests dead or dying cells and i. more rounded nucleus
tissue elements that need to be disposed off ii. with pseudopodia
 plays a major role in body’s non-immune or d. basophilic cytoplasm, and typically
inflammatory response (non-immune defense system) appears “frothy”
by engulfing and digesting invading microorganisms e. nucleus is usually indented and
and exogenous particle material densely staining and possesses a
 participates in body’s immune system by serving as prominent nucleolus
antigen-presenting cells (APCs).  in EM- numerous lysosomes
 present all over body; not just in connective tissue a. nucleus is dark and compact.
 other names:

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 HUMAN ANATOMY
EVALS 3
Lecture 2: Connective Tissue
Lecturer: Eduardo G. Gonzales, M.D.
PLASMA CELL COLLAGENOUS CONNECTIVE TISSUE
 Plasmocytes  a.k.a., ordinary connective tissue
 numerous in connective tissues that are accessible to  most abundant type in body
foreign proteins and bacteria (e.g., lamina propria of  predominant fiber is collagen fiber (collagen type I)
GIT)  predominant cell is fibroblast
 few in other connective tissues  types (on the basis of amount of ground substance and
 arises from B lymphocytes the number and arrangement of collagen fibers in the
 terminally differentiated cell intracellular matrix):
o incapable of cell division 1. dense collagenous connective tissue (dense
o cannot revert back to B lymphocytes. connective tissue)
 slightly bigger than RBC  scanty intercellular ground substance in which an
 nucleus abundant number of closely packed collagen fibers and
o eccentric relatively few cells are embedded,
o chromatin clumped and located near nuclear a) regular
membrane (“clock-face” or “cartwheel”  collagenous fibers arranged in definite pattern
appearance)  tendons, ligaments, fibrous membranes
 cytoplasm b) irregular
o basophilic  fibers run in various directions
o negative Golgi image often seen in H&E  dermis, capsule of some organs, sheath of nerves,
o ER is well developed (attesting to its periosteum, dura mater
secretory nature).
 function: 2. Loose collagenous connective tissue (loose
o produces antibodies connective tissue)
 antibody  Abundance of extracellular substance where the
o protein that is produced by plasma cells in relatively few collagenous fibers are arranged
response to an antigen or foreign substance haphazardly
(e.g., bacteria, viruses, etc.)  More cellular
o sole purpose is to help destroy specific  Dense CT has less cells; less ground substance; more
antigen that generated it. collagen fibers that are closely packed
o Binds to antigen that triggers its production  loose is more vascular
and by doing so, it is able to mark the antigen  a.k.a., areolar tissue
for destruction  more abundant in body than dense connective tissue
 life span: 10-20 days.  hypodermis (subcutaneous tissue), tunica adventitia of
blood vessels, lamina propria and submucosa of GIT,
LEUKOCYTES OR WHITE BLOOD CELLS respiratory and urogenital tracts
 five (5) types: neutrophils, basophils, eosinophils,
monocytes, and lymphocytes ADIPOSE TISSUE
 present in variable numbers in connective tissues  predominant cell is adipocyte
 post-natal life: produced in bone marrow and/or  functions:
lymphoid organs o largest energy storage site
 present in circulating blood, but perform function in  12-14% of body weight in males
connective tissue.  20-25% of body weight in females
 Escapes capillaries by ameboid movement  Fat stored in adipose tissue represents excess dietary
 Gather in inflamed areas caloric intake, hence, in overnourished individuals,
CONNECTIVE TISSUE CLASSIFICATION adipose tissue can comprise more than 25% of body
 Classification is based on cellular and extracellular weight.
composition  Inadequate caloric intake- stored energy in adipose
1. collagenous connective tissue cells released in form of fatty acids.
2. special types of connective tissue proper  thermal insulator (adipose tissue stored in the
o adipose tissue subcutaneous area)
o reticular tissue  shock absorber, e.g., soles of feet and around the
o elastic tissue kidneys
o mucous tissue  types:
o yellow (white) adipose tissue
 lipid stored as single fat vacuole

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 HUMAN ANATOMY
EVALS 3
Lecture 2: Connective Tissue
Lecturer: Eduardo G. Gonzales, M.D.
o brown adipose tissue
 lipid stored as numerous vacuoles
(droplets)
 color partly due to mitochondria
 2-5% of body weight in newborn,
mostly in neck and back
 almost absent in adult.
RETICULAR TISSUE
 main cellular element is reticular cell
 predominant fibrillar element is reticular fiber
 forms supporting framework (stroma) of
o liver
o hemopoietic tissue
o lymphoid tissues and organs (lymph nodes
and spleen)
ELASTIC TISSUE
 elastic fibers predominate
 elastic fibers often form bundles that are arranged
parallel to each other
 cells are mostly fibroblast
 found in:
o ligamentum flava of vertebral column
o suspensory ligament of penis
MUCOUS TISSUE
 ground substance
o abundant
o amorphous and jellylike
o mainly hyaluronic acid
 few fibers: collagen, elastic and reticular fibes
 few cells: mesenchymal cells, fibroblasts,
macrophages (present occasionally).
 common in embryo, rare in adults
 e.g., Wharton’s jelly – connective tissue of umbilical
cord

References:
 Powepoint Presentation
 Esteban and Gonzales’ Textbook of Histology

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