HUMAN ANATOMY 1

Epithelium, Connective Tissues, Cell Junctions

TYPES OF TISSUES
 Four (4) basic types of animal tissues
1. Epithelial
2. Connective
3. Muscular
4. Nervous

EPITHELIUM
 Epithelium is formed by closely apposed polygonal cells with little or no intercellular material that covers body surfaces or
form glands, associated with basement membrane.

TYPES

Type Location Main Function

Facilitates the movement of the viscera (Mesothelium)
Lining of vessels
Active transport by pinocytosis (Mesothelium and
(endothelium)
Simple Squamous endothelium)
Secretion of biologically active molecules
Serous lining of cavities
(Mesothelium)
Covering the ovary
Simple Cuboidal Covering, Secretion
Thyroid
Absorption of nutrient materials and fluids from the
filtrate that passes through the tubules
Simple Cuboidal with Brush Proximal and distal
Responsive to ADH and controls reabsorption of water
boarders convolutary tubules
from the glomerular filtrate, thus affect urine density,
and help retain water content of the body
Lining of intestine
Simple Columnar Protection, Lubrication, Absorption, Secretion
Gallbladder
Simple columnar epithelium Absorption - microvilli
with goblet cells and striated Small intestine Secretion of mucus - goblet cells
borders Protection from corrosive secretions of stomach
Lining of trachea Protection, Secretion
Pseudostratified Ciliated * Bronchi (*Nuclei lie at different levels which gives the impression
Nasal cavity that the membrane is composed of more than a layer of cells)
Bladder Allow distensibility of urinary organs without breaking
Ureter the cell contacts.
Transitional
Renal calyces (hence called Forms a protective osmotic border between urine in the
Urothelium) urinary bladder and underlying tissue fluids
Protection, Prevents water loss
Stratified Squamous (*cuboidal or columnar basal cells on basement membrane,
Epidermis
Keratinized* closer to the surface the cells become irregular in shape and
flatten, squamous)
Mouth
Esophagus Protection
Stratified Squamous,
Larynx Secretion
Non- Keratinized
Vagina Prevents water loss
anal canal

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Sweat glands Protection

Stratified Cuboidal
Developing ovarian follicles Secretion

Conjunctiva
Stratified Columnar Protection
Large ducts of salivary glands

Types of Epithelia

GLANDULAR EPITHELIA
 Formed by cells specialized to produce secretion

Types

Type Location

Based on the Number of Cells

Unicellular glands
Goblet cells
Consist of isolated glandular cells
Multicellular glands
Other Glands
Composed of clusters of cells
Based on the Morphology or Shape

Simple* Coiled Tubular Crypts of Lieberkühn

Simple Branched Tubular Sweat glands
Simple Acinar (Alveolar) Stage in the development of gland
Simple Branched Acinar Gastric glands

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*Have only one Unbranched duct

Testis
Compound** Tubular Liver
Kidneys
Salivary glands
Compound Tubuloacinar
Pancreas
**Have ducts that branch repeatedly
Simple Saccular*** Small sebaceous glands
Branched Saccular Big sebaceous glands
Compound Saccular Mammary glands
***Have saclike invaginations

Based on Integrity of Secretory Cells

Holocrine Glands
Sebaceous gland of skin
Cell is completely destructed in the process of secretion
Apocrine Glands Mammary gland
Apical part of cells together with cytoplasm disintegrates Atypical sweat glands
Merocrine Glands
Maintains the integrity of the cells and secretions are released Most of the other glands
by typical exocytosis
Based on Presence or Absence of Excretory Ducts
Endocrine Glands Most of the endocrine glands
Ductless glands, secretes directly into the blood stream Thyroid gland
Exocrine Glands Other glands

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Epithelium, Connective Tissues, Cell Junctions

CELL JUNCTIONS
 When one cell meets another, or with the extracellular matrix, specialized junctions may form at sites on the contacting
cell membranes

Types (Fig. 1.2)

I. Tight junctions (zonula occludens)
II. Adhesive junctions
A. Cell-to-cell
1. Zonula adherens
2. Macula adherens (desmosome)
B. Cell-to-matrix
1. Focal adhesions
2. Hemidesmosomes
III. Communicating (Gap) junctions

Terms
 Zonula – Junction that completely encircles the cell
 Macula – Patch like

Fig. 1.2 Type of Cell Junctions

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 At the molecular level, intercellular junctions comprise of 3 components

 A Transmembrane adhesive protein
 A Cytoplasmic adapter protein
 A Cytoskeletal filament
 Depending on type of junction, these components differ

1. Tight Junction (Zonula Occludens) (Fig. 1.3)

 Cell membranes of adjacent cells are held in close contact by anastomosing strands of transmembrane adhesive proteins
 Intercellular space is obliterated
 Transmembrane adhesive proteins include
 Occludin
 Claudin family
 Junctional Adhesion Molecules (JAM) - In some tissues
 These proteins interact with same type of proteins on adjacent cell membranes
 It controls the passage of material through the intercellular spaces
 It acts as a “Fence” to define apical and basolateral surfaces
 Tightness of the junction depends on
 Claudin present
 Number of strands of transmembrane protein
 Neurotransmitters and hormones

Fig. 1.3 Tight Junction

2. Adhesive Junction
 This junction holds either cell to cell or cell to extracellular matrix
 In Cell to Cell adhesive junction, the intercellular space is around 20 nm
 It is important in cell signaling
 Loss of this type of junction may lead to
 Apoptosis
 Loss of polarity of cell
 Loss of differentiation
 Unregulated cell proliferation
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Types
Cytoskeletal
Type of Adhesive Junction Transmembrane Protein Cytoplasmic Adapter Protein
Filament
Catenin Family
Cadherin Family  p120 Catenin: Stabilizes the
 Ca+2 dependent proteins junction
Zonula Adherens  Nectin: crucial role in  Afadin: links Nectin to Actin
Actin filaments
(Fig. 1. 4) establishing the initial  Vinculin and α – Actinin:
adhesion site and recruits E- Actin-binding proteins
Cadherin to the junction  Ponsin: links Afadin and
Vinculin
α – Catenin and β – Catenin:
Cell to Cell
E- Cadherin  Desmoplakin
 Desmoglein  Plakoglobin
 Desmocollin  Plakophilin
Macula Adherens
(Desmosome) Actin filaments
These proteins of adjacent cell These proteins form dense
(Fig. 1. 5)
membrane interaction results in plaque on cytoplasmic side of
dense line in the middle of the desmosome
intercellular space This plaque act as attachment site
for cytoskeletal filaments
Focal Adhesions
(Cell to
Integrin Family α-actinin, Vinculin, Talin Actin filaments
Extracellular
matrix) (Fig. 1. 6)
Cell to
Integrin Family
Matrix
Hemidesmosomes  Integrin α6β4: Binds to basal
Bullous pemphigoid antigen 230 Intermediate
(Cell to Basal lamina glycoproteins like
(BP230) and Plectin filaments
lamina) (Fig. 1. 7) Laminin and Collagen XVII
(BP180)

Fig. 1.4 Zonula Adherens

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Fig. 1.5 Macula Adherens

Fig. 1.6 Focal Adhesion

Fig. 1.7 Hemidesmosome

3. Gap Junction (Fig. 1.8)

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 Plaque like regions of cell membrane

 Intercellular space: 2 to 3 nm
 Transmembrane proteins
 Connexin family  Forms channels between the cytoplasm of the adjacent cells
 6 Connexin molecules forms a Connexon  has a central channel of 2 nm in diameter
 Connexons of one cell pair with those of adjacent cell  forms an open channel
 Small molecules – ions and signaling molecules - move from one cell to the other
 They couple the cells electrically

Fig. 1.8 Gap Junction

DISEASES ASSOCIATED WITH DEFECT IN INTERCELLULAR JUNCTIONS

Intercellular Junction Protein / Autoantibodies against Disease

Certain types of deafness
Congenital cataracts
A demyelinating disease (Charcot-Marie- Tooth)
Gap junction Genetic defect in Connexin protein
Oculodentodigital dysplasia - presents
craniofacial abnormalities, syndactyly, conductive
hearing loss, and hair and nail abnormalities
Genetic defect in Desmosomal,
Hemidesmosomal and Intermediate filament Epidermolysis bullosa
proteins
Adhesive Junction Genetic defect in Desmosomal proteins Pemphigus vulgaris
(Desmoglein-3 & Desmoglein-1) Pemphigus foliaceus
Autoantibodies against Hemidesmosomal
Bullous pemphigoid
components (Collagen XVII [BP180] & BP230)

CONNECTIVE TISSUE
 Function primarily to
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 Support the body

 Bind or connect all types of tissue
 Provides a mechanical framework (the skeleton) which plays an important role in locomotion
 It holds organs in place and attaches epithelial tissue to other underlying tissues.

Features Functions Components

Few cells Support CT cells
No basement membrane Protection Protein fibers
More of intercellular substances Transport (Collagen, Reticular, Elastin)
Majority take origin from the mesoderm (middle layer) Insulation Stromal components (Matrix)
Hematopoietic
Immunologic
Tissue repair

TYPES OF CONNECTIVE TISSUE

Connective Tissue Type Features Location

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Embryonic Connective Tissue

Vitreous of eye ball
 Found in adults
Pulp of teeth
Mesenchyme  Cell - primitive fibroblast, spindle shaped,
Nucleolus pulposes of
Mucous connective tissue stellate; abundance of ground substance
intervertebral disc
composed primarily of hyaluronic acid.
Wharton’s jelly of umbilical cord
Mature Connective Tissue
Loose Connective Tissue
Widely distributed, fewer collagen fibers, delicate
 Binding the epithelia to Superficial fascia
consistency, flexible, well vascularized, not very
other tissues, contributing Deep fascia
resistant to stress
to the formation of organs
Dense Regular / White Fibrous Tissue
Tendons
Dense Connective Tissue  Collagen fibers oriented unidirectional in
Ligaments
 Close packaging of response to prolonged stress, great resistance in
Aponeurosis
collagen fibers, adapted to traction forces
offer resistance and Dermis
protection, fewer cells, GIT mucosa
Dense Irregular
predominance of collagen Capsule of organs
 Collagen fibers in bundle, randomly oriented
fibers Periosteum
Perichondrium
Types
Parenchyma composing of adipocytes - large, oval 1. Yellow / white / unilocular -
shape, central fat surrounded by thin rim of subcutaneous tissue, around
cytoplasm containing nucleus - signet ring kidney, in various organs
Adipose Tissue
appearance. 2. Brown / multilocular / fetal
Functions: fat storage, insulation, mechanical adipocyte - animals that are
support hibernating, in fetus -- nape and
retroperitoneum
Appears in response to tensile strain with more
White Fibrous Tissue Ligaments, Tendons, Membranes
collagen fibres
Ligamenta flava, Ligamentum
Yellow Elastic Tissue Elastic fibres are predominant
nuchae, Vocal folds

Reticular Tissue With reticular fibres & reticular cells Lymph nodes, Spleen, Liver, Lungs

Supra choroid membrane, lamina

Pigment Connective Tissue Made up of pigment cells like melanocytes
fusca of sclera

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Mesenchyme Mucous Connective Tissue

Loose Connective Tissue Dense Regular Connective Tissue

Dense Irregular Connective Tissue Adipose Tissue

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White Fibrous Tissue
Reticular Tissue
CELLULAR COMPONENTS
Cell types
Fibroblast – Active Cell
Quiescent form – Fibrocyte
Macrophages / Histiocytes
Fat cells / Adipocytes
HUMAN ANATOMY 13
Epithelium, Connective Tissues, Cell Junctions
Yellow Elastic Tissue
Pigment Connective Tissue
Features Functions
Most common resident cells of CT
Synthesis of collagen fibers and
Fusiform or Spindle shaped
amorphous ground substances
Originate from mesenchymal cells
Has different names in different organs
Lungs - Alveolar Macrophage Engulfs bacteria
Blood - Monocyte Abundant in richly vascularized areas
Liver - Kupffer cell Important for defense
Bone - Osteoclast
Brain - Microglial cell
Lymph nodes - Dendritic cell
Skin - Langerhans cell
Heat production
Signet ring appearance
Storage of neutral fats
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Filled with basophilic secretory granules

(containing Heparin, Histamine, &
Releases chemical mediators
Mast Cells Serotonin)
Anaphylactic sensitivity reaction
Has a different name in the blood –
Basophil
Cartwheel appearing nucleus with Seen in inflammation
Plasma Cells
inclusion bodies called Russel bodies Major producer of antibodies

INTERCELLULAR SUBSTANCE/MATRIX
 Non-living material with two elements

Amorphous Elements / Ground Substance Fibrous

Polymers of carbohydrates & proteins Collagen fibres

Viscous, semi fluid material between cells & fibres, Proteoglycans, structural Elastic fibres
glycoproteins Reticular fibres

Ground Substance
 Highly hydrated, transparent, complex mixture of macromolecules: glycosaminoglycans (GAGs), proteoglycans, and
multiadhesive glycoproteins

Components Features

 Long polymers of hexosamine and uronic acid

 Hexosamine can be glucosamine or galactosamine
 Uronic acid can be glucuronate or iduronate
 Largest and most ubiquitous GAG is hyaluronan (also called hyaluronate or

Glycosaminoglycans (GAGs) - hyaluronic acid)

 Hyaluronan is synthesized directly by an enzyme complex, Hyaluronan synthase
Mucopolysaccharides
 Other GAGs are
1. Chondroitin sulphate
2. Dermatan sulphate
3. Keratin sulphate
4. Heparin sulphate

 Proteins with sulfated GAGs

Proteoglycans
 Examples are Perlecan, Aggrecan and Decorin

Large molecules with branched oligosaccharide chains and allow adhesion of cells to
Glycoproteins their substrate
Examples are Laminin, Fibronectin

Connective Tissue Fibers

Types Features Area of presence
I - Dermis, bone, tendon, fibro cartilage
Most numerous II - Hyaline, elastic
Collagen Fibers
Found as bundles III - Endomysium, smooth muscles, liver,
Known for rigidity
Bundles branch but not individual fibres spleen, kidney, lung.
IV - Basal lamina
Elastic Fibers Refractile fibers with Elastin Yellow ligaments of the vertebral column
Known for flexibility Fibres run singly, individual fiber branch, ends Suspensory ligaments of the penis
recoil, not visible - must be stained Bronchi
Trachea

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Hollow organs
Blood vessels

Reticular Fibers Trabecular system creates a sponge like Adipose

Supporting framework of structure within which cells and fluids are Muscle
hematopoietic and freely mobile, surrounds other tissues and cells, Basal lamina
lymphoid organs “argyrophillic" - black fibrillary strands. Stroma of glandular organs

COLLAGEN
 Most abundant protein in the body
 This superfamily comprises of at least 27 types of collagens
 Composed of 3 polypeptide alpha chains coiled around each other to for a triple helix configuration
 All types of collagens have in common
 Hydroxyproline and Hydroxylysine with the aminoacid Glycine at every 3rd position (Gly-X-Y repeating sequence)
 Non-collagenous domains
 Proline residues
 Chief producers of collagen are,
 Mesenchymal cells
 Their derivatives
o Fibroblasts
o Chondrocytes
o Osteoblasts
o Odontoblasts and
o Cementoblasts
 Minor amounts of collagen are produced by Epithelial cells, Endothelial cells, Muscle cells and Schwann cells

TYPES OF COLLAGEN
 Based on Supramolecular assemblies, Collagen superfamily is divided into 9 subfamilies

Subfamily Types of Collagens Salient Features

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I, II, III, V, XI, XXIV

 Form fibrils showing typical 64-nm banding pattern
Fibrillar Collagens and
 Most abundant type of collagen– Type I collagen
XXVII
 Size is like Type I collagen, but it does not assemble as fibrils
 Contains nonhelical sequences arranged in sheet like or chicken-
Basal Lamina collagen IV wire arrangement
 Major component of basal lamina – Type IV – Product of
epithelial cells
 Composed of chains of varying lengths and a variety of non-
collagenous domains
Fibril-associated collagens  Show several interruptions in triple helix
IX, XII, XIV, XVI, XIX,  Usually associated with Fibrillar collagens and other
with interrupted triple
XX, XXI and XXII extracellular matrix components
helices
 Type XIX collagen
 Found in basal lamina
 Crucial for skeletal muscle cell differentiation
Type VIII
 Assembles into hexagonal lattice
 Impart compressive strength
Network-forming  Provides open, porous meshwork
VIII and X
Collagens Type X
 Similar in size and structure as type VIII
 Restricted to hypertrophic zone of epiphyseal cartilage
growth plate
 Large nonhelical domains which makes up 2/3rds of size of the
molecule
Anchoring-fibril Collagen VII  C-terminal ends combine to form dimmers and assembles into
anchoring fibrils  extends from basal lamina into the
underlying connective tissue
 Has large N- and C- terminal globular domains that join in end –
Microfibril-forming to – end manner  beaded filaments
VI
collagen  Present in most connective tissues
 Has binding property for cells, proteoglycans
 These are transmembrane proteins with
 Extracellular – collagenous domain
 C – terminal non-collagenous domain  role in cell adhesion
Transmembrane XIII, XVII, XXIII and  Type XVII collagen: seen in Hemidesmosomes of basal
Collagens XXV epidermal cells and attaches these cells to basal lamina
 Type XIII collagen
 Seen in focal adhesion sites of fibroblasts
 Cell-cell adhesive specializations
 Have multiple interruptions in the central helical domain and a
large, unique C-terminal nonhelical domain
 C-terminal domain can be cleaved by extracellular proteases 
Multiplexin (endostatin-
XVIII, XV form Endostatin – potent inhibitor of endothelial cell migration
forming) Collagens
and angiogenesis
 Both collagens have glycosaminoglycan side chains  classified
as Proteoglycans
 Those that can’t be classified as other types
 Type XXVI – seen in extracellular matrix of testis and ovary
Other Collagens XXVI and XXVIII
 Type XXVIII – seen in basement membranes around Schwann
cells of the peripheral nervous system and dorsal root ganglia

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SYNTHESIS OF COLLAGEN

INHERITED DISEASES INVOLVING COLLAGEN

Mutations in Collagen genes Disease

Type I Osteogenesis imperfect/Brittle bone disease

Type I, Type III or Type V Ehlers-danlos syndrome
Type II or Type XI Stickler’s syndrome
Type IV Alport’s syndrome
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Type VII or Type XVII Epidermolysis bullosa

DEGRADATION OF COLLAGEN
 Involves two mechanisms
1. Extracellular degradation
2. Intracellular degradation

1. Extracellular Degradation
 Collagen triple helix is highly resistant to proteolytic degradation
 MMP (Matrix Metallo Proteinase) family – proteolytic enzymes that includes
 Collagenases (MMP-1, MMP-8, and MMP-13)
 Gelatinases (MMP-2 and MMP-9)
 Metalloelastase (MMP-12)
 Stromeolysins (MMP-3, MMP-10, and MMP-11)
 Matrilysins (MMP-7 and MMP-26)
 MMPs are synthesized by fibroblasts, inflammatory cells, some epithelial cells and tumor cells
 MT-MMPs (membrane type MMPs) also degrades collagen
 Extracellular degradation – occurs in inflammatory lesions & when rapid degradation of large amounts of collagen
occurs.
 Normal component of serum that inhibits MMPs – α2 – macroglobulin
 Fibroblasts are the cells which secrete both the activators and inhibitors of MMPs – regulates extracellular
degradation

MMPs – secreted as inactive precursors (proenzymes) and becomes active on proteolytic cleavage and MT- MMPs are in active
form intracellularly

Activate MMPs such as gelatinase A (MMP-2) & collagenase 3 (MMP-13)

Activated gelatinases + other extracellular proteinases in turn activate collagenases and other soluble MMPs

Cleavage of collagen molecules into 2 smaller fragments and are finally digested

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Fig. 1.9 Extracellular Degradation of Collagen

2. Intracellular Degradation
 Most important mechanism for physiologic turnover
Recognition of collagen fibril to be degraded via fibroblast integrin receptors

Partial digestion via gelatinase A (MMP-2)

Phagocytosis of fragments

Formation of phagolysosome

Digestion of collagen fibrils in acidic environment of lysosomes via cathepsins

CARTILAGE
 It is a special form of CT, rigid matrix but pliable and elastic
 Made up to cells and matrix, with collagen and elastic fibers in matrix, with perichondrium (dense regular fibrous CT)
 Avascular
 Function: provide structural support and degree of flexibility
 Histogenesis - formed by direct differentiation of mesenchymal cells in chondroblasts, chondroblasts multiply, grow and
produce cartilage matrix, surrounded by matrix and trapped in lacunae to mature into chondrocytes, CT fibers appear in
the matrix.
 Growth
1. Appositional Growth - new cells and matrix are added into the surface, increase in width by hypertrophy
2. Interstitial / Endogenous Growth - in the middle portion of the cartilage, multiplication of the chondrocytes and
production of new matrix from within which increase in size and length of cartilage by hyperplasia

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Hyaline Cartilage Elastic Cartilage

Fibrocartilage

Type of Cartilage Features Location

Embryonic cartilage - with perichondrium,

with young chondroblasts which are Skeletal model for bones developing by
numerous, small, irregular shape, minimal cartilage in fetus
matrix

Adult Hyaline - surrounded by the

Hyaline Cartilage
perichondrium; found in matrix:
 Most common type Respiratory system - nasal septum, laryngeal
chondrocytes in lacunae, cell nest, matrix
 Consists of type I and II cartilages like thyroid, cricoid, arytenoids
appears homogenous / glassy (because
collagen [except its apex], tracheobronchial tree.
refractive index of fibres is same as that of
 Transparent / translucent Costal cartilage is unique - prone for fibrous
matrix), interterritorial matrix and
changes
territorial/capsular matrix, collagen fibers
abundant in intercapsular matrix

Articular Hyaline- no perichondrium, more Between articulating surfaces of bones

and bigger chondrocytes, avascular developing from cartilage

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Elastic Cartilage
 Yellowish color -- due to
the presence of elastin
Fibrocartilage
*****
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At sites of sound reception (ear) - eustachian
With elastic fibers in the matrix, more tube, external auditory canal and sound
flexible, with perichondrium, fewer cell production (larynx)
nests Epiglottis, apex of arytenoids cartilage,
cuneiform cartilage in the larynx
Rich in tropocollagen, no perichondrium,
and scanty matrix with thick collagen fiber
Intervertebral disc, tendons and ligaments,
arranged in parallel bundles, chondrocytes -
symphysis pubis, first costochondral joint
smaller, fewer, arranged singly in rows
between bundles of collagen fibers.
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