1.

Characteristics of epithelial tissue

Tissue organized as sheets of cells which line/cover and form tubular structures
within organs.
Composed of cells and ECM (highly organized basement membrane)
Features: Various cell shapes + function, avascular, innervated, renewable, and
can undergo metaplasia (change into different types of epithelial tissue)
Cell shapes: Flattened, Cuboidal, Collumnar (nuclear form corresponds to shape)
Functions: Covering, lining + protecting surfaces (Epidermis)
Absorption (Intestinal lining)
Secretion and excretion (glands)
Contraction (myoepithelial cell)

2. Polarity of epithelial tissue and epithelial cell. Differences between

apical and baso-lateral domain.

Polarity relies on organelle distribution and membrane protein distribution
(membrane domains).
The region of the cell contacting the connective tissue is the basal pole (also
closest to basal lamina) and towards the free surface is the apical pole.
Differences in domains are usually due to protein and lipid distribution.
Apical domain: proteins enzymes, transporters and channels
Lipids Cholesterol and sphingomyelin
Baso-lateral domain: Proteins Na+/K+ ATP-ase, receptors, adhesion proteins
Lipids phosphatidylcholine, phosphatidylinositol

3. Specialisations of apical domain (cilia, microvilli, stereocilia)

Cilia
Long projecting structures which contain internal arrays of microtubules
Most cell types have at least one cillum (primary cillum) that is not motile.
Motile cilia are only found in epithelia 5-10 micrometres long and 2 micro wide
Consists of a core structure with 9 peripheral microtubular doublets, which form
an array around 2 central microtubules. This 9 + 2 assembly is an axoneme.
At the base of each cillum is a basal body, anchoring the axoneme to the apical
cytoplasm.
They are located in many places in the body e.g trachea, fallopian tube
Cilia beat in co-ordinated waves and brush foreign substances along (i.e mucus
in lungs) or move the ovum from ovary to the uterus in Fallopian tubes.
Microvilli
Projections of the apical pole. 1 micro long and 0.1 micro wide.
Contains bundle of actin filaments that are cross-linked
Located in epithelial cells specialized for absorption (i.e intestinal lining) and are
visible here as a brush border.
They may also assist in secreting enzymes for digestion i.e intestine.

Stereocilia
Resemble microvilli, containing arrays of actin filaments
However, they are much longer and less motile than microvilli.
Increasing surface area means that they have an increased capacity for
absorption. They are only located in epididymis and ductus deferens.

4. Specializations of the baso-lateral domain: intercellular junctions

There are 3 types: Tight junctions forms a seal between adjacent cells
Adherent junctions

Gap junctions channels for communication between adjacent

Cells
Of these, tight junctions are the most apical and at these junctions, adjacent
membranes appear fused. Seal is due to interaction of claudin and occluding.
The basal is the zonula adherens, where adhesion is mediated by cadherins.
It also encircles the epithelial cells. Involved in linking the actin cytoskeletons of
neighbouring cells. Another type of adherent junction is the desmosome/macula
adherens. They are disc-shaped structures that are matched with identical
structures at adjacent surfaces.
Basal domains of an epithelial cell attach to the subjacent basal lamina by
junctions call hemidesmosomes. They resemble a half-desmosome in TEM but
contain integrins rather than cadherins.
Gap junctions consist of transmembrane proteins called connexins that form
circular patches in membrances. When 2 cells attach, connexins in adjacent cell
membranes align to form connexons, wihich contains a central hydrophilic pore
that allows passage of small molecules.

5. Basal lamina and basement membrane

The basement membrane is a sheet of EC material at basal surface of epithelial
cells. It is visible in TEM as 2 structures:
Basal lamina electron dense layer nearest to basal pole
Reticular lamina
The basal lamina consists of laminin, type 4 collagen and an adhesive
glycoprotein such as entactin/nidogen or proteoglycans such as perlecan.
The basal lamina is made by molecules which are secreted by epithelial cells.
The reticular lamina consists of type VII collagen and fibronectin.
Its molecular composition is made by the connective tissue cells.

6. Classification of covering epithelia.

Epithelia can be functionally divided into 3 groups: Covering, glandular and
sensory epithelia.
Covering epithelia cover external surfaces and line cavities or internal organs.
Such epithelia can be classified by the no of layers:
Simple epithelia containing 1 layer
Stratified epithelia 2 or more layers

Furthermore they can also be classified based on cell shape:

Squamous flattened cells
Cuboidal width + thickness are similar/equal
Collumnar cells are taller than they are wide
The stratified squamous epithelia can also be keratinized/non-keratinized.
Furthermore, there are also 2 types of epithelia do not fall into this classification:
Transitional/urothelium
Pseudostratified columnar nuclei are disposed at different levels giving
appearance of stratified epithelia

7. Covering epithelia: Characteristics, location, function

Simple squamous epithelium consists of single layer of flattened cells, with
nuclei corresponding to cell shape.
Typically specialized as lining of vessels (endothelium) and cavities, where they
regulate passage of substances into underlying tissue.
They are also involved in serous lining of cavities: pericardium, pleura etc.
Their main functions are active transport by pinocytosis secretion of biologically
active molecule and facilitating the movement of viscera.
Simple cuboidal is a single layer of cells that are tall as they are wide. They are
mainly located in the ovary, kidney tubules and thyroid. Due to its greater
thickness, the cytoplasm is rich in mitochondria and other organelles for high
levels of active transport.
Simple cuboidal is a single layer of cells that are taller than wide, with apical cilia
or microvilli. They line the intestine, digestive tract and fallopian tubes. Due to
apical specializations, they are often specialized for absorption. Complexes of
tight and adherent junctions are also present at apical ends.
8. Pseudostratified epithelium: Characteristics, location, function

9. Stratified squamous keratinized epithelium:

Characteristics,location,function

The very thin apical surface of stratified squamous epithelium epithelia can be
keratinized, which means filled with keratin intermediate filaments.
It cells form many layers, with the less differentiated cuboidal cells near the
underlying connective tissue.
They become more irregular and flatten in shape as they accumulate keratin and
move progressively closer to skin surface, where they become thin, metabolically
inactive packets (squames) of keratin, which lack nuclei.
This surface layer of cells protects against dehydration and is located in areas
such as skin.

10. Stratified squamous non-keratinized epithelium.

These cells generally line wet cavities such as the mouth, esophagus and vagina,
where water loss is not a problem.
Here, the flattened cells of the surface layer contain much less keratin, retaining
their nuclei and metabolic function.
The keratinizing system consists of continuous renewal of epithelium of the
epithelium by 4 overlapping processes: mitosis, keratinization, cell death,
exfoliation.

11. Stratified cuboidal and columnar epithelia

2 or more layers of cuboidal/columnar cells.
Both are relatively rare, consisting of several layers of each type of epithelia.
Cuboidal epithelia are mainly located in sweat glands and excretory ducts, where
its main role is protection and secretion.
Columnar epithelia are mainly located in the conjunctiva lining the eyelids where
is both protective and mucus secreting.

12. Transitional epithelium

13. Endocrine glandular epithelium

Group of epithelial cells specialized for secretion that have no connection with
the surface: completely surrounded by connective tissue.
They eliminate their secretory product directly into the bloodstream.
They can be classified according to:
Cell grouping: Anastamosing cords, follicles, islets and isolated cells
Secretory product: small polypeptides, proteins or cholesterol derived
Moment of release: immediate, or after storage

14. Exocrine glandular epithelium

Group of epithelial cells specialized for secretion that forms glands in contact
with free surface of epithelium by an excretory duct.
They eliminate product through an excretory duct.
They can be classified based on:
No of cells Unicellular or multicellular gland
Shape of duct: simple unbranched or compound unbranched
Shape of secretory region: tubular, coiled tubular or branched tubular
Acinar or branched acinar
Mixed (tubuloacinar)
Secretory product: Mucous product rich in glycoproteins

Serous protein secreting

Mixed

15. Cells specialized for protein synthesis (Serous cells)

Exocrine glands with merocrine secretion can be separated into mucous or
serous according to secretory product. Serous glands secrete proteins.
These protein secreting cells have a basal pole rich in RER, a round central
nucleus, rich in Golgi just above nucleus and have zymogen granules at their
apical pole.
Serous acini refers to the termination of the exocrine gland where the secretion
is produced.
These cells secretion includes enzymes (pancreas, salivary glands) and
hormones (parathyroid-PTH)

16. Cells specialized for glycoprotein synthesis (mucous cells)

Exocrine glands with merocrine secretion can be separated into mucous or
serous according to secretory product.
Mucous cells have a basal pole containing the nucleus and organelles (RER,golgi
etc.) and an apical pole with secretory granules.
They release heavily glycosylated proteins called mucins.
When the mucins are released from the cell, they become hydrated and form
mucus.
Mucous secreting cells include goblet cells, and mucous acini in salivary glands.

17. Cells specialized for lipid synthesis

Special type of epithelial cells

- Location:

Exocrine Cells

Sebaceous gland (secretes sebum)
- Sebum is the product of holocrine secretion. The entire cell produces and
becomes filled with the fatty product while it simultaneously undergoes
programmed cell death (apoptosis) as the product fills the cell.

Endocrine Cells

Leydig Cells- Testis
Large, polygonal, eosinophilic cells that typically contain lipid droplets
Elaborate smooth endoplasmic reticulum (sER), a feature that accounts for their
eosinophilia
The enzymes necessary for the synthesis of testosterone from cholesterol are
associated with the sER.

Follicular Cells Ovary

When a primordial follicle begins the changes leading to the formation of a

mature follicle, the layer of squamous follicular cells becomes cuboidal, as in this
figure. In addition, the
follicular cells proliferate and become multilayered.

Adrenal Cortex Cells

18. Cells specialized for small peptide and amine synthesis

19. Cells specialized for ion transport

20. Myoepithelial cell

Epithelia of many exocrine glands (e.g salivary,sweat) contain contractile
myoepithelial cells, located inside the basal lamina around the basal end of the
secretory cells.
Long processes embrace around an acinus, whereas they are more longitudinally
arranged in ducts.
They are connected to each other and to the other epithelial cells by gap
junctions and desmosomes.
They are rich in actin filaments and myosin.
Their contractions help propel secretory products into, and up the duct system.

21. Merocrine, apocrine and holocrine secretion.

Epithelial cells in multicellular exocrine glands have 3 main releasing
mechanisms:
Merocrine Most common method, involves exocytosis of the product
from membrane bound vesicles e.g salivary gland
Apocrine product accumulates at cells apical end. Portions of apical
membrane, cytoplasm and the product are then released into the lumen
of gland. E.g lipid droplet secretion in mammary gland.
Holocrine Cells accumulate product as they mature and undergo
differentiation, culminating in complete cell disruption with release of
product and cell debris into lumen e.g sebaceous gland in skin

22. Definition, basic structure and function of connective tissues.

One of the 4 basic types of tissues.
Composed of cells, fibers and GS. The amount of each of these components
defines what type of connective tissue is.
All connective tissue has a common embryological origin (mesoderm).
Major constituent is the ECM (fibers and GS).
They are innervated and vascularized (cartilage is only exception with no
capillary bed.
They provide structural support (bone & cartilage), defense (non-specific and
immune), are important in cell growth + differentiation and provide insulation
(adipose tissue).

23. Structure and ultrastructure of connective tissue fibers: collagen,

elastin and reticulin

Collagen and reticular fibers consist of collagen proteins. Elastic fibers come
from elastin proteins.
Collagen is secreted by fibroblasts as procollagen, which then aggregates to form
fibers. It consists of 3 protein chains wrapped around each other and cross-
linked. In the TEM, collagen fibrils have alternating light and dark bands
longitudinally (which exhibit an 68nm repeating pattern), and appear as dots
surrounded by GS in cross sections.
In the light microscope they appear as fibrils.
Reticular fibers are also made of collagen, but mainly type 3.
It forms a network of extremely thin fibers, also exhibiting a 68 nm banding
pattern. They are displayed using the PAS reaction, with a thread-like
appearance.
Elastic fibers are made from the protein elastin. They are thinner than collagen
fibers and arranged in a branching pattern to form a network. They are
commonly interwoven with collagen fibers to limit distensibility of tissue they
are in. Consists of a central elastic core and surrounding network of fibrillin
microfibrils.
The elastin appears as an amorphous structure of low electron density.

24. Collagen biosynthesis

Formation of mRNA for each type of alpha chain

Synthesis of alpha chains of preprocollagen. Clipping of signal peptide
Hydroxylation of amino acid (prolyl and lysyl) residues in ER. This step is
vitamin C dependent.
Attachment of galactosyl and glucosyl to hydroxylysyl residues.
Assembly of procollagen molecules
Registration peptides
Transport of procollagen to the Golgi
Secretory vesicles (assisted by microtubules and filaments) transport
procollagen to the cell surface.

Discharge of procollagen into the EC space. Peptides cleave and transform

procollage into tropocollagen, which aggregates to form collagen fibrils.
Fibrilar structure is reinforced by formation of covalent cross-links
between tropocollagen molecules.

25. Collagen types

Several classes of collagen are identified on the basis of their polymerization
pattern:
Fibrilar collagens type 1, 2, 3, 5 and 11. Form 68nm banding pattern
Fibril associated collagen type 9 and 12. Have interruptions in their
triple helixes to allow for measure of flexibility.
Network forming collagens 8 and 10
Transmembrane collagens 13 and 17
In total, there are 28 different classes of collagen.

26. Ground substance: molecular composition and function

Part of the ECM that occupies space between cells and fibers.
Participates in binding cells to fibers.
Consists predominantly of 3 groups of molecules:
Proteoglycans, GAGs and multiadhesive glycoproteins
GAGs are long polysaccharides consisting of repeating disaccharide units, usually
a uronic acid and a hexosamine. They are responsible for many of the physical
properties of the GS, allowing rapid diffusion of water soluble molecules and
providing a structural framework for the cells.
Proteoglycans composed of GAGs covalently attached to core protein.
Finally, GS also consists of cell adhesion proteins such as fibronectin, which
binds cells, collagen & GAGs, and laminin, which mediates attachment of
epithelial cell to basal lamina.

27.Connective tissue cells - classification

28. Fibroblast/Fibrocyte

The fibroblast is the principal cell of the connective tissue.
They are responsible for the synthesis of collagen and reticular fibers, and the
complex carbohydrates in GS.
Two levels of fibroblast activity can be observed histologically.
Cells higher activity are the fibroblast, and contain a larger, more euchromatic
nucleus. Cells with less activity are the fibrocytes, and are smaller, with a more
heterochromatic nucleus.

They can freely change between these 2 states and the fibroblast often can
induce differentiation of surrounding cells.
Furthermore fibroblasts involved in wound healing called myofibroblasts show
the properties of both smooth muscle cells and fibroblasts. It is associated with
actin and has a contractile function.

29. Uniocular/white adipocyte

Large mesenchymally derived cell specialized for cytoplasmic storage of lipids.

Termed uniocular because the triglycerides are contained within a large single
lipid droplet which takes up the majority of the cell.
Because of its large size, the lipid droplet displaces and flattens the nucleus
against the cell membrane, giving it a signet ring appearance with a thin rim of
cytoplasm also associated with the nucleus.
Most of the cytoplasm surrounds the nucleus and contains small golgi, RER etc.
The membranous layer surrounding the lipid droplet contains cisternae of SER
and pinocytotic vesicles.

30. Multiocular/brown adipocyte

Large mesenchymally derived cell specialized for cytoplasmic storage of lipids.

Termed ultiocular because the adipocytes contain many small lipid inclusions.
The cells are polygonal and generally smaller than white adipose tissue. Their
nuclei are often centrally located.
The brown colour is mainly due to very abundant mitochondria (containing
cytochrome) and the large no of capillaries.
The many lipid droplets, mitochondria and capillaries all help mediate the
prinicipal function of brown adipose tissue, which is thermogenesis in non-
shivering mammals such as newborns, who have a substantial amount of brown
adipose tissue.

31. Reticular cell: Structure, Ultrastructure, Functions

A reticular cell is a type of fibroblast that synthesizes type III collagen and uses it
to produce reticular fibres.
Star-shaped cells with long and thin processes that establish anchoring junctions
with neighbouring cells; round, central, pale nucleus. Consists of mainly of
collagen type III, which forms extensive networks of extremely thin (diameters
0.52 m) and heavily glycosylated fibres in certain organs. The reticular
cells surround the reticular fibres with its cytoplasm, isolating it from other
tissue components and cells.
Produce reticular fibres, which form the fine structural network of organs such as the
lymph nodes, spleen and bone marrow, support to soft organs.
Should not be confused with the reticulocyte, an immature erythrocyte


32. Macrophage: structure,ultrastructure,functions
a) Structure:
they are part of the mononuclear phagocyte system(MPS/RES)
30 micrometer, ruffled membrane (irregular shapes), acidophilic
lysosomes in the cytoplasm; can have various heterogenous inclusions -
-- ingested material
Reound, oval or kidney_shaped,eccentric nucleus; can have nucleoli
Derived from the peripheral blood monocytes, involved in phagocytosis
and inflammatory response
Has various shapes,localizations and names (e.g.: Histiocytes!connective
tissue;Kupffer Cells!liver;langerhans cells!intraepidermal,
osteoclasts!bone ..etc.)
b) Ultrastructure:
numerous lysosomes, phagosomes and pseudopodia
abundant RER, SER, Mitochondria and Golgi complexes
c) Function:
Mainly phagocytosis
Triggered by a specific interaction between membrane receptors and
ligands
Consequences: ! cell movement towards target particle
!pseudopodia formation engulfment
!respiratory burst
!secretion: cytokines, interferon,completement and
coagulation factors
!production of matrix metalloproteinases
33. Mast Cell: structure,ultrastructure,functions
Localized in most of the loose connective tissue areas along blood vessels
a) Structure:
Large oval cell, 20-30 micrometer
Cytoplasm has numerous basophilic metachromatic
granules(elements of a cell stain in a different color from that of the
dye solution in a different color from that of the dye solution- toluidine
blue)
Round, small and central nucleus
b) ultrastructure:
Granules, an extensive golgi complex, cisternae of RER, free ribosomes,
mitochondria and numerous microvili and folds
c) Function:
Granules contain heparin or chondroitin sulfate, histamine, eosinphil
chemotactic factors.. etc.
Conten can be released! degranulation; the process is triggered by
chem./physical stimuli, or through binding of antigen-IgE-complexes
by specialized receptors
Degranulation is mediated by cAMP and leads also to leukotriene
synthesis

34. Plasma Cell: structure, ultrastructure, functions

a) Structure:
Ovoid/pear-shaped cells
Basophilic cytoplasm (due to abundant RER), with a perinuclear pale area (Golgi
apparatus); can contain acidophilic Russel bodies (secretory granules)
Eccentric nucleus, with hetero- and euchromatin in a characteristic pattern:
cart wheel or clockface (the heterochromatin resembling the spokes of the
wheel or the numbers on a clock), visible nucleolus.
b) Ultrastructure:
extensive Golgi complex, abundant RER, secretory granules (Russel bodies), free
ribosomes and mitochondria.

c) Function:
Found in lymphoid organs (lymph nodes, spleen, bone marrow) and connective
tissues associated to the respiratory and digestive mucosae

Originate in B lymphocytes, that are terminally differentiated as a response to

antigen challenge

Secrete immunoglobulins (antibodies): IgM, IgG, IgA, IgE

Part IV. Varieties of Connective Tissues



35. Classification of connective tissue

!based on the composition and organisation of ist components and on ist functions

Embryonic connective tissue: I. mesenchyme
II. mucous connective tissue
Adult connective tissue(connective tissue proper): I. loose(areolar) CT
II. dense(fibrous)
(regular/irregular) CT
III. reticular CT
IV. elastic CT
Specialized connective tissue: I. adipose tissue
II. cartilage
III. bone
IV. hematoproetic tissue (bone marrow)
CT has following elements: 1) Ground substance 2) Fibers 3) Cells

36.Loose connective tissue: structure and localization:

a) structure:
More abundant than dense CT
comprises all the main components of CT proper, in equal portions
all types of cells; most numerous: fibroblasts, macrophages
collagen, elastic small proportion of reticular fibers
abundant ground substance
flexible, very well vascularized , not very resistant to stress
b) Localisation:

 supports epithelial tissues

ensheathes the lymphatic and blood vessels
papillary layer of the dermis
serosal linings of peritoneal and pleural cavities
glands and mucous membranes
37. Dense irregular connective tissue: structure+localization
a) structure:
has fewer cells, mainly fibrocytes, occasional mast cells and macrophages
clear dominance of collagen fibers
little ground substance
less flexible (dense CT in general)
DENSE IRREGULAR! collagen fibers in bundles without a definite orientation
3D-Network! resistant to stress from all directions
b) localization:
Capsules of the parenchimatose organs
Dermis#submucosa of digestive tract
Periosteum
Perichondrium

38. Tendon: structure + localization

a) Structure:
Elongated cylindrical structures
Rich in collagen fibers! white and inextensible
Parallel,closely packed bundles of collagen
Small quantities of amorphous intercellular substance
Fibrocytes= tendocytes
The collagen bundles primary bundles!loos connective tissue =
endotenonium
Aggregate in larger bundles secondary bundles ! loose connective tissue with
blood vessels and nerves = peritoneum
Externally, the tendon is surrounded by a sheath of dense connective tissue =
epitoneum
b) Localization:
Attaches striated muscles to bones

39. Aponeuroses: structure + localization

a) Structure:
Inextensible structure that attaches striated muscle to bones (flat?)
Predominance of thick collagen fibers
Multiple layers: 1) Parallel to same layer 2) perpendicular on the collagen fibers
from the layer beneath and above!textile aspect
Fibrocytes, flattened, narrow-shaped
b) Localization:
Attaches striated muscle to flat bones

40. Reticular connective tissue: structure + localization

a)structure:
Specialized loose CT
Framework(stroma) of the myeloid( bine marrow) and lymphoid tissue
Supports soft organs

41. Elastic tissue: structure, localization

Structure:
Predominance of thick, parallel elastic fibres, in between are
rare collagen fibres and flattened fibroblast.
The elastic fiber is formed from the elastic microfibril
(consisting of numerous proteins such as microfibrillar-
associated glycoproteins, fibrillin, fibullin, and the elastin
receptor) and amorphous elastin.

Localisation:

Yellow ligament of the neck
Suspensory ligament of the penis.
Layers of elastic fibres in blood vessels.
Lungs
Bladder
Skin

42. Mucous tissue: structure, localization
Considered under embryonic connective tissue. It is loose and
irregular connective tissue

Structure:

Gelatin- like extra cellular matrix
Abundance of amorphous ground substance (whartons
Jelly)
Thin collagen Fibres
Spindle shaped cells

Localisation:
Found in umbilical cord

43. White adipose tissue: structure, localization, function

Basically composed of fat cells and thin layers of loose irregular
connective tissue.
Structure:
White unilocular adipose
Spherical (isolated) and polyhedral (in the tissue)
Flattened nucleus
Have a rim of cytoplasm
Small amounts of collagen and elastic fibres
Small amount of ground substance.
Colour (white to dark yellow).
Location:
Throughout the human body
The distribution and density of the tissue is sex and age
determined. ( Hips on women and abdomen on men).
Function:
Insulation
Fat pads for organ protection.
44. Brown adipose tissue: structure, localization, function
Generates body heat in new borns.
Structure:
Multilocular tissue cells
Polygonal and smaller than white adipose
Well vascularised
Spherical, central nucleus
Cytoplasm: Greater number of lipid droplets of
different sizes and numerous mitochondria with
abundant long cristae.
Location
Large amounts in newborns
Scarce in adults
Except the perirenal, periaortic, cervical and
mediastinum regions.

45. Hyaline Cartilage: structure, localization

Structure:
Hyaline cartilage consists of a bluish-white, shiny ground
elastic material with a matrix of chondroitin sulphate into
which many fine collagen fibrils are embedded. It contains
numerous chondrocytes.

Location:
Embryonic skeleton (fetus)
Articular surface of the joint
Trachea
Bronchus
Nose
Larynx

46. Elastic Cartilage: structure, localization
Structure:
Cells in large numbers compared to hyaline
In small isogenous groups( 2-3 cells)
Smaller spaces between cells
Matrix has type II collagen fibrils
Perichondrium is present
Location:
Epiglotis
Larynx
Pinna of the ear
Auditory canal
Eustachian Canal

47. Fibrous Cartilage: structure, localization

Structure:
Cells: Rare chondrocytes, small isogenous groups
arranged in long rows
Fibers: Numerous, Type 1 collagen fibres ,
irregular/aligned in parallel arrangement
Ground substance: Less abundant
No perichondrium.
Location:
Intervertebral disks
Pubic symphysis
Some articular cartilages
Associated to dense connective tissue in ligaments and
tendon.
48. Chondroblast, and chondrocyte: structure, ultrastructure,
localization
Chondroblast Immature:
Structure LM:
Nucleus: Round, euchromatic, 1-2 nucleoli
Cytoplasm: Basophilic , juxtanuclear pale region
Found near perichondrium
Can be isolated in groups
Ultrastructure EM:
Rough endloplasmic reticulum
Golgi complex
Mitochondria
Glycogen
Lipid droplets
Many short cytoplasmic projections

Chondrocyte Mature:
Structure LM:
Oval nucleus (one or two nucleoli)
Cytoplasm: Acidophilic
Far from perichondrium.
Ultrastructure EM:
Synthesis and secretion of components in extracellular matrix
Few organelles
Euchromatin and heterochromatin on nucleus
49. General histological structure of osseous tissue types.
Osseous tissue, or bone tissue, is the major structural and supportive
connective tissue of the body. Osseous tissue forms the rigid part of the
bones that make up the skeletal system.
Bone tissue is a mineralized connective tissue. It is formed by cells,
called osteoblasts, that deposit a matrix of Type-I collagen and also
release calcium, magnesium, and phosphate ions that ultimately combine
chemically within the collagenous matrix into a crystalline mineral,
known as bone mineral, in the form of hydroxyapatite. The combination
of hard mineral and flexible collagen makes bone harder and stronger
than cartilage without being brittle.
There are two types of osseous tissue: compact and spongy. Compact
tissue is synonymous with cortical bone, and spongy tissue is
synonymous with trabecular and cancellous bone. Compact bone forms
the extremely hard exterior while spongy bone fills the hollow interior.
The tissues are biologically identical; the difference is in how the
microstructure is arranged.

50. Osteoblast, osteocyte, osteoclast: structure, ultrastructure,

functions
Osteoblast: synthesis the organic components of the matrix
Structure:
Shape: Columnar, cuboidal (matrix synthesis), flattened when
inactive.
Nucleus: pale stained, Nucleoli
Cytoplasm: Basophilic
Ultrastructure:
Rough endoplasmic reticulum
Golgi complex
Mitochondria
Function:
Synthesis of the organic components of the matrix=osteoid.
Growing factors (autocrine/paracrine)
Receptors for hormones and vitamins
Stimulating factors for osteoclasts.
Osteocyte:
Represent inactive osteoblast trapped within formed bone (1 cell per
lacuna) between layers (lamellae) of bone matrix
Structure:
Shape: Flattened and elongated
Nucleus: Flattened, condensed chromatin
Cytoplasm: Basophilic/ acidophilic
Ultrastucture:
When compared with osteoblasts, the flat, almond-shaped osteocytes
exhibit a significantly reduced RER and Golgi apparatus and more
condensed nuclear chromatin. Have long thin cytoplasmic processes.
Function:
These cells are involved in maintaining the bony matrix and their death is
followed by resorption of this matrix.

Osteoclast:
Structure and ultrastructure:
Very large (20-150 m)
Multinucleated (20-150 nuclei)
Acidophilic cytoplasm
Clear zone (actin): site of adhesion to bone
Vesicles zone: lysosomes
Nuclei zone + organelles (mitochondria, golgi and RER)
Function:
Osteoclast re absorption contributes to bone remodeling in
response to growth or mechanical stress on skeleton.
51. Intramembranous ossification
One of the ways in which bones are formed initially (other is
endochondrial ossification)
Osteoblasts differentiate directly from mesenchyme and begin secreting
osteoid. It is the direct replacement of mesenchyme by bone in
vascularised zones. In both processes, the bone tissue that appears first is
primary or woven. Primary bone is a temporary and is soon replaced by
the definitive secondary lamellar bone. During bone growth, areas of
primary bone, areas of resorption, and areas of secondary bone all appear
side by side.
Most of the flat bones are produced by membranous ossification and it
takes place within condensations of embryonic mesenchymal tissue. The
frontal and parietal bones of the skull as well as parts of the occipital and
temporal bones and the mandible and maxilla are formed by
intramembranous ossification.
The starting point for bone formation is called an ossification center. The
process begins when groups of mesenchymal cells differentiate into
osteoblasts. Osteoblasts produce osteoid matrix and calcification follows,
resulting in the encapsulation of some osteoblasts, which then become
osteocytes. These islands of developing bone form walls that delineate
elongated cavities containing capillaries, bone marrow cells, and
undifferentiated cells. Several such groups arise almost simultaneously at
the ossification center, and their fusion between the walls gives the bone
a spongy appearance. The connective tissue that remains among the bone
walls is penetrated by growing blood vessels and additional
undifferentiated mesenchymal cells, giving rise to the bone marrow.

52. Endochondral bone formation

Takes place within a piece of hyaline cartilage whose shape resembles a
small version, or model of the bone to be formed. This type of
ossification is principally responsible for the formation of short and long
bones.
This cartilage model continues to grow by both interstitial and
appositional means, and primarily is used to form the short and long
bones. As development progresses, the chondrocytes divide, hypertrophy
(enlarge), and mature, and the hya- line cartilage model begins to calcify.
As calcification of the cartilage model continues, diffusion of nutrients
and gases through the calcified matrix decreases. Consequently,
chondrocytes die, and the fragmented calcified matrix serves as a
structural framework for the deposition of bony material.
As soon as a layer of bony material is deposited around the calcifying
cartilage, the inner peri- chondrial cells exhibit their osteogenic potential,
and a thin periosteal collar of bone forms around the midpoint of the shaft
of the bone. This external surrounding connective tissue is now called the
periosteum. Mesenchyme cells differentiate into osteoprogenitor cells
from the inner layer of periosteum, and blood vessels from the
periosteum invade the calcified and degenerating cartilage model.
Osteoprogenitor cells proliferate and differentiate into osteoblasts that
secrete the osteoid matrix, a soft initially collagenous tissue that lacks
minerals but is quickly mineralized into the bone. The osteoblasts are
then surrounded by bone in the cavelike lacunae and are now called
osteocytes; there is one osteocyte per lacuna. Osteocytes establish a
complex cell-to-cell connection through tiny canals in the bone called
canaliculi; these eventually open into channels that house the blood
vessels. Osteoprogenitor cells also arise from the inner surface of bone
called endosteum. Endosteum lines all internal cavities in the bone and
consists of a single layer of osteoprogenitor cells.
Mesenchyme tissue, osteoblasts, and blood vessels form a primary
ossification center in the developing bone that first appears in the
diaphysis or the shaft of the long bone, followed by a secondary
ossification center in the epiphysis or the articular surface of the
expanded end. In all developing long bones, cartilage in the diaphysis and
epiphysis is replaced by bone, except in the epiphyseal plate region,
which is located between the diaphysis and epiphysis. Growth in this
region continues and is responsible for lengthening the bone until bone
growth stops. Expansion of the two ossification centers eventually
replaces all cartilage with bone, including the epiphyseal plate. The only
exceptions are the free or articulating ends of long bones. Here, a layer of
perma- nent hyaline cartilage covers the bone and is called the articular
cartilage.

BLOOD
53. Erythrocytes
Erythrocytes or red blood cells are non nucleated cells and are the most
numerous blood cells. They are one of the three of formed elements in the
blood (others are leukocytes WBC and platelets). They are the most
abundant element.
Erythrocytes (red blood cells) are terminally differentiated, lack nuclei,
and are packed with the O2-carrying protein hemoglobin. Under normal
conditions, these corpuscles never leave the circulatory system.
Like most mammalian red blood cells, human erythrocytes suspended in
an isotonic medium are flexible biconcave disks. They are approximately
7.5 m in diameter, 2.6 m thick at the rim, and only 0.75 m thick in the
center. This biconcave shape provides a large surface-to-volume ratio and
facilitates gas exchange. The normal concentration of erythrocytes in
blood is approximately 3.95.5 million per micro litre in women and 4.1
6 million per micro-litre in men.

Contain haemoglobin with iron molecules in cytoplasm

Carry oxygen as oxyhaemoglobin and carbon dioxide as carbaminohemoglobin
Biconcave shape increases surface area to carry respiratory
gases
Life span is about 120 days, after which cells are phagocytosed in
spleen, liver, and bone marrow
No mitochondria so the generate ATP anaerobically

Disorders:

Decrease in oxygen carrying capacity

Increased destruction (Haemolytic)
Decreased production
Anaemia

54. Differential count of blood leukocytes

The aim of the count is to indicate what type of disease a patient may
have if any. A sample of venous blood is obtained with one drop placed
on a slide in order to prepare a blood smear. Using a light microscope 100
blood cells are counted noting each leukocyte and their frequency.
Normal quantities in blood:
Neutrophils = 48-66%
Eosinophils = 1-4 %
Basophils = 0-0.5 %
Monocytes = 8%
Lymphocytes = 25-27%
Pathological results and indications:
An increase in:
Neutrophils = acute bacterial inflammation
Eosinophils = allergic reaction, parasitic infection, chronic inflammation
Basophils = Allergic reaction so basophils release histamine
Lymphocytes = in viral infections and tumour cells.
55. Neutrophil: structure, ultrastructure and functions
Structure:
12-15 m diameter
are spherical in shape
Nucleus:
- Multi-lobed nucleus (2 5).
- Number of lobes increases with cell age (hyper-segmented cells).
- Human females may have inactivated second X chromosome
(Barr corpuscle drumstick) (3%)
Cytoplasm - acidophilic
- Neutrally stained specific granules
- Non-specific granules (lysosomes) are azurophilic
Ultrastructure:
Heterochromatic nucleus
Cytoplasm has: RER, Golgi Apparatus, mitochondria, lysosomes
Granules: Lysosome, Lactoferin, collagenase.
Function:
play a central role in inflammatory processes
follow chemotaxic signals to wound sites or other inflammation
leave the blood diapedesis
phagocytose foreign agents such as bacteria
First wave if cells invading infection sites.

56. Basophil: structure, ultrastructure and functions

Structure LM:
12-15 m diameter
Are spherical in shape
Nucleus:
U- or S-shaped nuclei with 2 - 3 lobes
Cytoplasm - acidophilic
basophilic stained specific granules
large, irregular shape purplish-black
non-specific granules are azurophilic
Ultrastructure:
Specific granules
- heparin,
- histamine inflammatory chemical that acts as a
vasodilator
- leukotriens
Azurophilic granules - lysosomes
Function:
The function is related to that of mast cells
Allergies and anaphylaxis (hypersensitivity reaction)
- binding of antigens to membrane-bound IgE antibodies
induces degranulation of specific granules, which leads to
allergic reaction.
- in hypersensitivity reaction, widespread vasodilation
(arteriolar) and vessel leakiness induce circulatory shock.
Bronchial spasms cause respiratory insufficiency; combined
effect is anaphylactic shock.

57. Eosinophil: structure, ultrastructure and functions

Structure :
12-15 m diameter
Spherical in shape
Nucleus (bi-lobed)
Cytoplasm (acidophilic)
- acidophilic (red-orange) stained specific granules
- non specific granules are azurophilic.
Ultrastructure:
Heterochromatic nucleus
Few organelles

 Specific granules (light zone at the periphery and dark zone in the
middle)
Function:
Kills parasites (especially helminthic parasites
Associated with allergic reactions
Phagocytose Ag-Ab complexes formed in allergy
Implicated in chronic inflammation
Corticosteroids decrease Eosinophils in blood
58. Monocyte : structure, ultrastructure and functions
Structure:
12-20 m diameter
Nucleus : Oval or kidney shaped, eccentric
Cytoplasm: Basophilic (blue)
- Azurophilic granules.
About 16 m in smears, thus the largest leukocyte. Large, eccentric
nucleus either oval, kidney-shaped or horseshoe-shaped, with delicate
chromatin that is less dense than that of lymphocytes. Pale cytoplasm,
often grayish, may contain occasional stained granules (lysosomes =
azurophilic granules). Large lymphocytes may resemble monocytes, but
the lymphocyte nucleus is usually more dense.
Ultrastructure:
Azurophilic Granule (lysosome)
Centriole
Mitochondria
Golgi
Function:
Respond by chemotaxis to the presence of factors from damaged
tissues, microorganisms and inflammation by migration into the
tissues and differentiating into macrophages.
Constitute mono-nuclear phagocyte system
Mediate inflammatory response (phagocyte bacteria, other cells
and tissue debris).
Antigen presenting cells: dendritic cells, Langerhans cells.

59. Lymphocyte: structure, ultrastructure and functions

Structure:
6-8 m diameter (small) up to 15 m (Large)
Round, dark, large heterochromatic nucleus.
Thin layer of basophilic, non-granular cytoplasm.
3 Types B, T and NK
Ultrastucture:
Mitochondria
Centriole
Cytoplasm doesnt appear to be very active
Free ribosomes.
Function:
Lymphocytes vary in life span according to their specific functions; some
live only a few days and others survive in the circulating blood or other
tissues for many years. They are the only type of leukocytes that,
following diapedesis, can return from the tissues back to the blood.
Lymphocytes have diverse functional roles related to immune defense
against invading microorganisms, foreign or abnormal antigens, and
cancer cells.
Essential in immunologic defense of organism
When exposed to specific antigens, B lymphocytes form
plasma cells in connective tissue
Plasma cells release antibodies to counteract or destroy
invading organisms
B lymphocytes:
Are involved in humoral immunity
Differentiate into plasma cells
Involved in production of antibodies
T lymphocytes:
T helper (express CD4, critical for induction of immune response).
T suppressor (express CD8, CD45RA, suppress antibody formation
by B cell and down regulate the ability of T lymphocyte to initiate
immune response).
T cytotoxic (Express CD8, primary effector cell in cellular
mediated immunity, require interaction with T h cells to get
activated. Detect virus-infected cells.

60. Platelet : structure, ultrastructure and functions

150.000-400.000 /l. They are fragments of megakaryocyte cytoplasm
with a life span of 10 days in blood.
Structure:
2-5 m diameter
Round or oval
Non-nucleated
Cytoplasm ( light blue, dark blue/purple granules)
Ultrastructure:
Peripheral zone: ( plasma membrane, mictrotubule, actin and
myosin filaments)
Organelle zone: Mitochondria, peroxisomes, glycogen particles,
granules ( alpha, lambda, delta granules)
-Alpha: contain fibrinogen, coagulation factors, plasminogen,
platelet derived growth factor.The play an important role in the
initial phase of vessel repair, blood coagulation and platelet
aggregation.
- Lamda: similar to lysosomes and function in clot resorbtion
-Delta: Smaller, denser and less numerous, contain ADP, ATP and
facilitate platelet adhesion and vasoconstriction in the area of
injured vessel.
Membrane system: interconnected canalicular system.
Function:
Form plugs to occlude sites of vascular damage by adhering to the
collagenous fibres at the margin of the wound. Later this plug is
reinforced by fibrin.
They promote clot formation by providing a surface for the
assembly of coagulation protein complex.
Secrete factors that modulate coagulation and vascular repair.

HEMATOPOIESIS
61. Bone Marrow: Structure and Function
- Bone marrow is found in the mdullary canals of long bone and the small
cavities of cancellous bone
- 2 types (Based on gross appearance)
Blood-forming red bone marrow Contains 2 types of stem cells

1) Hematopoietic
2) Stromal
Yellow bone marrow filled with adipocytes that exclude most
hematopoietic cells

- At birth, all bone marrow is red but becomes more yellow as you age
- Red bone marrow contains a reticular connective tissue stroma, hematopoetic
cords/islands of cells and sinusoidal capillaries
- The stroma = Network of specialized fibroblastic cells called reticular cells +
delicate web of reticular fibers supporting the hematopoietic stem cells
- The matrix of bone marrow also contains collagen type I fibers, proteoglycans,
fibronectin and laminin
Main function:

Hematopoietic - to produce blood cells



Stromal to produce fat, cartilage and bone

62. Hematopoietic Stem Cells

- All blood cells arise from a single major type of pluripotent stem cells in the
bone marrow that can give rise to all the cell types
- These cells proliferate to form 2 major lineages of the progenitor cells:
One for lymphoid cells (lymphocytes)
One for myeloid cells (marrow)
- These develop in bone marrow
-Myeloid cells include:
granulocytes, monocytes, erythrocytes and
megakaryocytes
-These lymphoid progenitors migrate from bone marrow to thymus/other
lymphoid structures where they proliferate and differentiate
- Progenitor cells for blood cells are called colony forming units (CFUs)
- 4 Major types:

1) CFU-erythrocytes
2) CFU-megakaryocytes
3) CFU-granuloctes
4) CFU-lymphocytes

63. Intrauterine Hematopoiesis

- Blood cells appear in circulation during or 3rd week of development
- Their numbers increase as they divide repeatedly
- Separated into 3 phases:
1) Prehepatic phase human blood stem cells develop from mesoderm of
the yolk sac and allantois. Only cells of the red cell lineage are present

2) Hepatosplenothymic phase- Begins in the 2nd month blood forms in

the mesenchyme within the liver and late in the spleen and thymus. The
liver produces precursor cells of granulocytes, megakaryocytes and
erythroblass until its activity decreases (around 4th or 5th month)
3) Medullolymphatic phase begins once bone marrow and lymph nodes
develop. Clavicle is the first bone to exhibit hematopoietic activity. The
marrow of other bones soon follow. By the 5th month, bone marrow
becomes the predominant hematopoietic tissue.

64. Erythropoiesis

- Erythropoeis = formation of erythrocytes

- Erythrocytes develop from the multipotential myeloid stem cell CFU-GEMM
(Colony forming units - Granulocyte Erythrocyte Macrophage Monocyte) under
the influence of erythropoietin (protein)
- 1st recognizable precursor cell = proerythroblast which comes from CFU-E
- Proerythroblast = large cell with large sphical nucleus and basophilic cytoplasm
- Next = Basophillic erythroblast more strongly basophilic and has a more
condensed nucleus
- The basophilia of these 2 cells is caused by large number of polysomes
synthesisizing hemoglobin
- During the next stage, cell volumes and polysome number decrease and some
cytoplasmic areas begin to fill with hemoglobin, producing acidophilic and
basophilic regions = Polychromatophatophillic erythroblast
- Then the cell and nucleus volumes continue to condense and no basophillia is
evident, resulting in an acidophilic cytoplasm = Orthochromatophillic
erythroblast (Normoblast)
- Late in this stage, the cell ejects its nucleus which is then phagocytosed by
macrophages
- The cell still has a few polyribosomes which form a faintly stained network
The resulting cell is = Reticulocyte
- Reticulocytes pass to the circulation, quickly lose their polyribosomes and
mature as Erythrocytes
- This process takes approximately 1 week

65. Granulopoiesis

- Granulopoiesis = formation of granulocytes

- Involves cytoplasmic changes dominated by synthesis of proteins for
azurophillic granules and specific granules
- They all originate form the multipotent CFU-GEMM stem cell
- Its induced to differentiate into CFU-GM (Neutrophil) by factors such as GM-
CSF, G-CSF and IL-3
- It differentiates into CFU-Eo by factors such as GM-CSF, IL-3 and IL-5
- Lack of IL-5 causes it to differentiate into CFU-Ba
- The azurophillic granules are made initially, and are the same in all 3
granulocytes.
- This is followed by production of the specific granules whose contents differ in
each type of cell, giving them certain different properties.

- The myeoblast = first recognizable cell with no cytoplasmic granules and faint
nucleoli
- In the next stage, the promyelocyte is characterized by a basophilic cytoplasm
and azurophillic granule. Different promyelocytes activate different genes
resulting in 3 lineages.
- The first visible sign of this differentiation appears in the myelocyte in which
specific granules gradually increase and eventually occupy most of the cytoplasm
in the metanomyelocyte.
- These neutrophillic , basophilic and easinophillic metamyelocytes mature with
further condensations of the nuclei
- Before its complete maturation, the neutriphillic granulocyte passes through an
intermediate stage, the band cell, where the nuclei is elongated but not yet
polymorphic.

66. Lymphopoiesis

- Lymphopoiesis = formation of lymphocytes

- Although lymphocytes originate mainly in the thymus and peripheral lymph
organs (spleen, lymph nodes, etc.), all progenitor cells originate in the bone
marrow.
- Some of these lymphocytes migrate to the thymus, where they acquire
properties of T lymphocytes
- Subsequently, T lymphocytes populate specific regions of peripheral lymphoid
organs
- The first progenitor of lymphoid cells = Lymphoblast a large cell capable of
dividing 2 or 3 times to form a lymphocyte
- As lymphocytes develop, their nuclei become much smaller and cells decrease
in size
- In bone marrow and thymus these cells synthesize the specific cell surface
proteins that characterize B or T lymphocytes

67. Monopoiesis

- Monopoiesis = formation of monocytes

- Also differentiates from the multipotent CFU-GEMM stem cell
- Produced from the CFU-GM under stimulation by GM-CSF, IL-3 and M-CSF
- The monoblast = progenitor cell and is virtually identical to the myeoblast,
containing no cytoplasmic granules and faint nuclei
- Further differentiaton leads to the promonocyte a large cell with basophilic
cytoplasm and slightly identical nucleus
- Promonocytes divide twice as they develop into monocytes
- Differentiating monocytes contain extensive RER and Golgi forming lysosomes
which are observed as azurophillic granules at maturity
- Monocytes circulate in blood and entertissue where they mature as
macrophages

68. Megakaryocytes and Platelet formation

- Thrombocytes orginate in red bone marrow by dissociating from mature

megakaryocytes which in turn differentiate from megakaryoblasts in a process
driven by thrombopoietin
- The megakaryoblast has a kidney-shaped nucleus with several small nucleoli

- Before differentiating, the cells undergo endomitosis with repeated rounds of

DNA replication not separated by cell divisions resulting in a highly polypoid
nucleus (shape of polyp or hydra)- the cytoplasm is basophilic
- Megakaryocytes = giant cells up to 150m in diameter with large polyploidy
nuclei, coarse chromatin and no visible nucleoli. Cytoplasm with mitochondira,
RER and Golgi
- To form platelets, megakaryocytes extend several branching processes called
proplatelets.
- These extensions penetrate the sinusoidal endothelium and are exposed into
the circulating blood of sinusoids
- Internally, proplatelets have actin filaments and microtubules
- A loop of microtubules forms an enlargement at the distal end of the proplatelet
and the cytoplasm in these loops is pinched off to form platelets
- Mature megakaryocytes have invaginations of plasma membrane throughout
the cytoplasm called demarcation membranes which are thought to represent a
membrane reservoir that facilitates the continous rapid proplatelet elongation.

MUSCLE TISSUE
69. Structure of skeletal muscle tissue

- Consists of muscle fibers which are long, cylindrical multinucleated cells with
diameters of 10 to 100m
- Elongated nuclei are found peripherally just under the sarcolemma
- A small reservoir of progenitor cells called satellite cells are found adjacent to
most fibers of differentiated skeletal muscle
- 3 types of skeletal muscle fibers are described
1) Type I - Slow oxidative
2) Type II a Fast oxidative glycolytic
3) Type II b Fast glycolytic
- Characterised by cross-striations in longitudinal sections
- Alternating light and dark bands A band in I band.
- In cross sections they are polygonal with nuclei at periphery and connective
tissue between cells

70. The connective tissue sheaths of striated skeletal muscle

- Thin layers of connective tissue surround both individual muscle fibers and
bundles of muscle fibers
- At the end of the muscle, the connective tissuecontinues as a tendon and
attaches the muscle to a bone (usually)
- The connective tissue associated with muscle is:
Endomysium delicate layer of reticular fibers that surrounds individual
muscle fibers. In addition to nerve fibers, capillaries form a rich network
in the endomysium, bringing O2 to the muscle fibers
Perimysium thicker connective tissue layer that surrounds a group of
fibers to form a bundle/fascicle. Each fascicle makes up a functional unit
of muscle fibers

Epimysium Sheath of dense connective tissue that surrounds a

collection of fascicles that constitutes the muscle. Contains the larger
nervers, blood and lymphatics of the muscle.

71. Myoneural junction structure and ultrastructure
- also called the neuromuscular junction
- Myelinatated axons of motor nerves branch out in the perimysium where each
nerve gives rise to several unmyelinated terminal twigs that pass through
endomysium and form synapses with individual muscle fibers
- Each axonal branch loses their myelin sheath and forms a dilated termination
situated within a trough on the muscle cell surface.
- this synaptic structure is nthe NMJ/ motor end plate.
- Within the axon terminal are mitochondria and vesicles containing Ach
- Between the axon and muscle is a space = the synaptic cleft
- The sarcolemma is thrown into deep junctional folds which provides greater
postsynaptic surface area and more Ach receptors
- A neuron along with the specific muscle fibers that it innervates is a motor unit

72. Outline the ultrastructural organization of skeletal muscle fiber
- Each muscle fiber is filled with longitudinal subunits called myofibril
- Myofibrils are composed of bundles of myofilaments, which are polymers of
myosin II and actin
- The functional unit of a myofibril is the sarcomere which extends between 2
lines. It consists of alternating A (Dark) and I (Light) bandsby a well developed
smooth ER called the sarcoplasmic reticulum
- The myofibrils are anchored to the inner surface of the sarcolemma
(FOR THIS QUESTION, ALSO INCLUDE PARTS OF THE NEXT 3 QUESTIONS AS
THEY ARE DIRECTLY RELATED TO THIS ONE)

73. Ultrastructure and molecular organization of sarcomere

- Functional unit of the myofibril extending between two Z lines.

- Measures 2 to 3m but can stretch to >4m and reduce to 1m in contraction
- The arrangement of thick and thin filaments gives rise to density differences
that produce the cross striations
- The myosin containing thick filaments are located centrally in the sarcomere
and termed the A band
- The thin filaments attach to the Z line and extend into the A band to the edge of
the H band
- Poritons of 2 sarcomeres, on either side of a Z line, constitute the I band and
contain only thin filaments
- The Z line appears as a zig-zag structure; it anchors the thin filaments from
adjacent sarcomeres to the angles of the zig-zag

74. Sarcoplasmic reticulum Ultrastructure and function

- In skeletal muscle, it is specialized for Ca2+ sequestration

- Depolarization of the sarcoplasmic reticulum membrane, which causes release
of Ca2+, is initiated at the motor end plates.

- To trigger Ca2+ release from the SR throughout fiber simultaneously and cause
uniform contraction of all myofibrils, the sarcolemma is folded into T tubules
- Adjacent to each side of every T tubule are expanded terminal cisternae of the
SR
- This complex of T tubule + 2 Cisternae = Triad
- After depolarization of SR membrane, Ca2+ ions in the cisternae are released
into the cytoplasm surrounding thick and thin filaments
- Ca2+ binds troponin and allows briding between actin and myosin molecules
- When the membrane depolarization ends, the SR pups Ca2+ back into the
cisternae, ending contractile activity
- Together, the triad components make up a signaling apparatus to convert
repeated cell membrane depolarizations into spikes of free Ca2+that trigger
contraction

75. Particular aspects of the sarcolemma in skeletal muscle fiber

- Name given to the cell membrane of a skeletal muscle fiber cell

- Covered by a basal membrane consisting of basal and reticular lamina
- Has several particularities:
To trigger Ca2+ release from SR throughout the fiber simultaneously and
cause uniform contraction of all myofibrils, sarcolemma is folded into a
system of T tubules. These finger- like invaginations penetrate deeply into
the sarcoplasm and encircle every myofibril near the aligned A and I band
of sarcomeres. Adjacent to each T tubule are 2 terminal cisternae of the
SR- These 3 elements form the triad (T tubule + 2 Cisternae)
At the neuromuscular junction, the sarcolemma has numerous deep
junctional folds which provide for greater post synaptic surface area and
more transmembrane Ach receptors

76. Molecular events in contraction mechanism and contraction

regulation of striated muscle
- Contraction mechanism begins with a nerve impulse arriving at NMJ triggering
release of Ach receptors in the motor end plate, initiating a muscle impulse in the
sarcollema of the muscle fiber
- The impulse spreads from sarcollema along the T tubles, and Ca2+ ions are
released from terminal cisternae into the sarcoplasm
- Ca2+ binds to troponin which changes shape moving tropomyosin on the actin
to expose active sites on actin molecules of thin filaments
- Myosin heads of thick filaments attach to these active sites and form cross-
bridges
- ATP binds myosin and is hydrolyzed to ADP + Pi
- Myosin heads detach from thin filaments and return to original position
- This repeating cycle of attach-pivot-detach-return slides thick and thin
filaments past each other
- The sarcomere shortens and the muscle contracts
- When the impulse stops, Ca2+ ions are actively transported into the SR,
tropomyosin re-covers active sites, and filaments passively slide back to relaxed
state.

- Regulation involves Ca2+, SR and T-tubules

- Ca2+ must be available for the reaction between actin and myosin and the
terminal cisternae in the SR act as reservoirs
- They also contain abundant Ca2+ channels, mitochondria and glycogen
- T-tubules contain depolarization-sensitive transmembrane channels that are
active when sarcolemma is depolarized
- Conformational changes of these proteins affect Ca2+ channels located in the
terminal cisternae (Triggers release of Ca2+ from channels)

77. Histophysiological types of skeletal muscle

- 3 types of skeletal muscle fibers:

Type I (slow oxidative fibers) Small fibers that contain many
mitochondria, myoglobin and cytochrome complexes. They are slow-
twitch fatigue resistant motor units. They have great resistance to fatigue
but generate the least tension and have the lowest myosin ATP-ase
reaction velocity. Typically found in long muscles of back (posture) and
long distance runners

Type IIa (fast oxidative glycolytic fibers) Intermediate fibers that also
have many mitochondria and myoglobin. However, they can undergo
anaerobic glycolysis. They make up fast-twitch fatigue resistant motor
units and are seen in high proportions in the 400m/800m runners

Type IIb - (fast glycolytic fibers) - Large fibers that contain less
myoglobin and mitochondria. They have a low amound of axidative
enzymes but high anaerobic activity and considerable glycogen stores.
They are fast-twitch fatigue prone motor units and generate most muscle
tension but fatigue rapidly due to lactic acid build up. Seen in higher
proportions in short distance sprinters and weight lifters.

78. Regeneration of skeletal muscle fibers

- Satellite cells are interposed between the plasma membrane of muscular

fiber and its external lamina
- Satellite cells = small cells with a small quantity of cytoplasm, single nucleus
and a chromatin network denser and coarser than muscle cell nuclei
- Satellite cells are responsible for the skeletal muscles ability to regenerate
but their regenerative capacity is limited
- These myogenic precursors of muscle cells are normally inactive and do not
express MRFs (Myogenic regulatory factors)
- However after injury of muscle tissue, some satellite cells become activated,
reenter the cell cycle and begin to express MRFs
- They proliferate and give rise to new myoblasts
- As long as the external lamina is intact, the myoblasts fuse within the
external lamina to form myotubes which mature into a new fiber.
- In contrast, if the external lamina is disrupted, fibroblasts repair the
injured site with subsequent scar tissue formation.

79. Structure of cardiac muscle

- Type of striated muscle similar to skeletal but consists of individual cylindrical

cells, each containing 1 or 2 centrally located nuclei
- Cardiac fibers consist of cells in a series with interlinking processes where they
are held together
- Cells within a fiber often branch and bind to cells in adjacent fibers and
therefore, the heart consists of tightly knit and interwoven bundles of cells
- The regions of contact are called intercalated discs and represent the boundary
between adjacent muscle cells
- The discs contain desmosomes in their transverse regions and gap junctions in
their longitudinal regions
- Two desmosomes serve to bind cells tightly together and prevent their pulling
apart under constant contractile activity
- The gap junctions provide ionic continuity between cells, serving as electrical
synapses and allow cardiac muscle to act like a multinucleated syncytium
(multinucleate cell which can result from multiple cell fusions of uninuclear
cells)

80. Outline the ultrastructural organization of cardiac muscle fiber

- In the TEM, it is impossible to see the abundant mitochondria which occupy

40% of cytoplasmic volume
- There are also numerous lipid droplets which contain triglycerides as fuel for
the heart
- The cardiac muscles also contain T-tubules from the sarcolemma and are only
associated with 1 expanded terminal cistern of the SR (Sarcoplasmic reticulum),
forming a dyad (rather than the triad seen in skeletal muscle)
- In atrial muscle cells, it is also possible to find cytoplasmic granules containing
ANF (Atrial Neuretic Factor)

81. Conduction system of the heart. Structure and Ultrastructure of

Purkinje fibers
- Consists of specialized cardiac cells which generate the impulse for the heart
beat pacemaker cells
- They are SA node, AV node and Bundle of His
- Cardiac muscle does not rely on nerve activity to begin contraction =
involuntary muscle
- SA node is the primary pacemaker of the heart
- These nodes consist of P cells which have a clear cytoplasm and a large, central
nucleus
- They have no T tubules and sarce contractile filaments and desmosomes
- Purkinje fibers are specialized fibers extending from atria ! ventriclular
septum and lateral ventricle walls
- They are larger than cardiac muscle cells and form a network embedded in
dense connective tissue
- They contain 1-2 nuclei, display peripheral cross-striations, they dont contain
any intercalated disc and have a clear central area in each sarcoplasm and are
rich in mitochondria and glycogen granules

82. Structure of smooth muscle tissue

- Smooth muscle fibers consist of individual, small fusiform (tapering) cells that
are linked by numerous gap junctions
- They are non-striated cells enclosed by a basal lamina and a fine network of
reticular fibers (endomysium)
- Each cell has a single long nucleus centrally located
- There are short membrane invaginations called caveolae that are often present
at cell surface

83. Ultrastructual organization of smooth muscle fibers

- Consists of spare SR but they lack T tubules

- The caveolae contain several pumps and ion channels
- Consists of bundles of thick and thin myofilament criss-crossed obliquely
through the cell
- Have an elaborate array of 10 nm intermediate filaments usually composed of
desmin
- The intermediate filaments and F-actin filaments both insert into dense bodies
(which contain -actinin and are functionally similar to Z-discs of striated and
cardiac muscle.

84. Molecular events in contration mechanism and contraction

regulation of smooth muscle
- The characteristic contractile activity of smooth muscle is generated by
myofibrillar arrays of actin and myosin
- The bundles of thin and thick myofilament criss-cross obliquely through the cell
- The actin filaments use calmodulin and Ca2+ sensitive myosin light chain kinase
(MLCK) instead of fraponin in contraction mechanism
- Smooth muscle is not under voluntary control and contraction is regulated
differently in viscera, airways or blood vessels.
- Regulation can involve autonomic nerves, through swellings of axons with
synaptic vesicles which lie near sarcollemma or hormones
- Smooth muscles receives adrenergic and cholinergic nerve endings that can
stimulate/depress its activity

85. Types of smooth muscle cells

Visceral (single unit) cells

- connected by gap junctions

- Network receives single innervations and contract together
- They are arranged in layers in the walls of cavitary organs
- Show rhythmic contraction cycles in absence of neural stimulation

Multiunit cells
- Each fiber innervated and contracts separately
- Located around large blood vessels and airways. Iris of eye etc.

86. Classification of neurons, examples of particular types of neurons.

(John)


1. Shape of cell body: pyramidal, star-shaped, granular
2. Size

large > 100m,
small 10 m
3. No. of processes (**examples highlighted below)
unipolar
bipolar
multipolar

4. Type of released neurotransmitter

5.

Function
Sensory (afferent) transmit impulses toward the CNS
Motor (efferent) carry impulses away from the CNS
Interneurons (association neurons) lie between sensory and motor
pathways and shuttle signals through CNS pathways

87. Structure and ultrastructure of different types of neuroglia: astrocytes,

oligodendrocytes, microglia, ependymal cells.

In General:

Type of Neuroglia
Astrocytes:
- Link between neurons and
capillaries

Structure and ultrastructure

Largest of the neuroglial cells
Do not form myelin
Star-shaped with many processes
Two kinds of astrocytes identified;
Protoplasmic astrocytes
- Are more prevalent in the outer
most covering of brain called gray
matter.
- These astrocytes have numerous,
short, branching cytoplasmic
Fibrous astrocytes
- are more common in the inner
core of the brain called white
matter.
- These astrocytes have fewer
processes, and they are relatively
straight


Oligodendrocytes:
- Appear in specially stained light
- Cell responsible for producing CNS
microscopic preparations as small
myelin.
cells with relatively few
- The myelin sheath in the CNS is
processes compared with
formed by concentric layers of
astrocytes
oligodendrocyte plasma membrane
- Small round, nuclei, with

processes surrounding one axon

or several nearby axons

" The nucleus-containing region of
Found in both white and gray matter
the oligodendrocyte may be at
- Majority of CNS cellularity (most
some distance from the axons it
common)
myelinates
Microglia
Small,
Phagocytic cells
- smallest of the neuroglial cells

Elongated cells
- have relatively small, elongated

Ependymal cells
Form the epithelium-like lining of the
fluid- filled cavities of the CNS
- Line the central cavities of the
brain and spinal column

nuclei
Short, irregular processes
- When stained with heavy metals,
microglia exhibit short, twisted
processes

Ultrastructure:
- TEM reveals numerous lysosomes,
inclusions, and vesicles.
- However, microglia contain little
rER and few microtubules or actin
filaments
Form a single layer of cuboidal/
columnar cells that have the morphologic
and physiologic
characteristics of fluid-transporting cells
- Many are ciliated
They are tightly bound by junctional
complexes located at the apical
surfaces.
- Tight junctions at apical pole,
Ultrastructure:
At the TEM level, the basal cell surface
exhibits numerous infoldings that
interdigitate with adjacent astrocyte
processes.
- The apical surface of the cell
possesses cilia and microvilli.
- The latter are involved in
absorbing cerebrospinal fluid.
- The modified ependymal cells and
associated capillaries are called
the choroid plexus




88. General organization of a neuron. Axonal transport

Features:
1. Nerve cell body (Perikaryon or
Soma)

The cell body of a neuron has characteristics
of a proteinproducing
cell.

Characteristics
- Contains the nucleus and a nucleolus
-

The major biosynthetic center

Has no centrioles

Has well-developed Nissl bodies

(rough ER)

Axon hillock cone-shaped area where
axons arise; contains Na voltage-gated
channels, responsible for action potential
initiation
- lacks large cytoplasmic organelles
and serves as a landmarkto
distinguish between axons and

dendrites in both light microscopy

and TEM

2. Axon
Axons are effector processes that transmit
stimuli to other neurons or effector cells.

3. Dendrites
Dendrites are receptor processes that
receive stimuli from other neurons or from
the external environment.

1 per soma

Initial segment from axon hillock

Transmits AP away from soma

No Nissl bodies or Golgi cisternae

However; Microtubules,
neurofilaments, mitochondria, and
vesicles pass through the axon
hillock into the axon

Axon collaterals
Axon terminals
- They have a greater diameter than
axons, are unmyelinated, are usually
tapered, and form extensive
arborizations called dendritic trees.
-

Dendritic trees significantly increase

the receptor surface area of a
neuron.

Contents of the perinuclear

cytoplasm of the cell

body and cytoplasm of dendrites are similar,

with the exception of the Golgi apparatus.

Axonal transport;

Newly synthesized protein molecules are transported to distant locations within a
neuron in a process referred to as axonal transport


Most neurons possess elaborate axonal and dendritic processes.

Because the synthetic activity of the neuron is concentrated in the nerve cell body,
axonal transport is required to convey newly synthesized material to the processes.
Axonal transport is a bidirectional mechanism;
- It serves as a mode of intracellular communication, carrying molecules and
information along the microtubules and intermediate filaments from the
axon terminal to the nerve cell body and from the nerve cell body to the axon
terminal.


Anterograde transport carries material from the nerve cell body to the periphery.
- Kinesin, a microtubule-associated motor protein that uses ATP, is involved in
anterograde transport
Retrograde transport carries material from the axon terminal and the dendrites to
the nerve cell body.
- This transport is mediated by another microtubule-associated motor protein,
dynein

Transport Type
Fast anterograde

Speed (mm/day)
~ 400

Mechanism
Material Transported
Saltatory
1. Mitochondria;
movement along
2. Vesicles
microtubules by the
motor molecule
containing peptide
kinesin (ATP
3. neurotransmitters,
dependent)
4. some destructive
enzymes

Fast retrograde

Slow anterograde

~200-300

~0.2-8

Saltatory
movement along
microtubules by the
motor molecule
dynein (ATP
dependent)

1. Degraded
vesicular
membrane

Not clear; possibly

by molecular
motors

1. Cytoskeletal
elements (e.g.,
neurofilament and

2. Absorbed
exogenous
material (toxins,
viruses, growth
factors)

microtubule
subunits)
2. Soluble proteins of
intermediary
metabolism
3. Actin

89. Classification of synapses

Synapse:
-A junction that mediates information transfer from one neuron to another neuron
or to an effector cell

Classification:

1. Location

axodendritic, occurring between axons and dendrites;

axosomatic, occurring between axons and the cell body; or

axoaxonic, occurring between axons and axons

2. Mechanism of conduction

Chemical synapses:
- Conduction of impulses is achieved by the release of chemical substances
(neurotransmitters) from the presynaptic neuron.
-

Neurotransmitters then diffuse across the narrow intercellular space that

separates the presynaptic neuron from the postsynaptic neuron or target
cell.

Electrical synapses:
- Common in invertebrates, these synapses contain gap junctions that permit
movement of ions between cells and consequently permit the direct spread
of electrical current from one cell to another.

These synapses do not require neurotransmitters for their function.

Mammalian equivalents of electrical synapses include gap junctions in

smooth muscle and cardiac muscle cells

3. Response of postsynaptic membrane

The release of neurotransmitter by the presynaptic component can cause either
excitation or inhibition at the postsynaptic membrane.
- In excitatory synapses, release of neurotransmitters such as acetylcholine,
glutamine, or serotonin opens transmitter-gated Na_ channels (or other
cation channels), prompting an influx of Na_ that causes local reversal of
voltage of the postsynaptic membrane to a threshold level (depolarization).
This leads to initiation of an action potential and generation of a nerve
impulse.
-

In inhibitory synapses, release of neurotransmitters such as (GABA) or

glycine opens transmitter-gated Cl_ channels (or other anion channels),
causing Cl to enter the cell and hyperpolarize the postsynaptic membrane,
making it even more negative. In these synapses, the generation of an action
potential then becomes more difficult.

4. Type of neurotransmitter

*Same as above


90. Describe the structure of a chemical synapse
A typical chemical synapse contains a presynaptic element, synaptic cleft, and
postsynaptic membrane.

A presynaptic element (presynaptic knob, presynaptic component, or synaptic
bouton) is the end of the neuron process from which neurotransmitters are
released.

The presynaptic element is characterized by the presence of synaptic

vesicles, membrane-bound structures that range from 30 to 100 nm in
diameter and contain neurotransmitters

Presynaptic density/Active zone: electron dense thickening of the

presynaptic membrane, where synaptic vesicles accumulate/dock and where
neurotransmitters are released

Numerous small mitochondria are also present in the presynaptic element

The synaptic cleft is the 20- to 30-nm space that separates the presynaptic neuron
from the postsynaptic neuron or target cell, which the neurotransmitter must cross.
-

Fluid-filled space separating the presynaptic and postsynaptic neurons,

prevents nerve impulses from directly passing from one neuron to the next

Transmission across the synaptic cleft:

Chemical event
Ensures unidirectional communication between neurons
The postsynaptic membrane (postsynaptic component) contains receptor sites with
which the neurotransmitter interacts.
-

This component is formed from a portion of the plasma membrane of the

postsynaptic neuron and is characterized by an underlying layer of dense
material.

postsynaptic density: represents an elaborate complex of interlinked

proteins that serve numerous functions such as

1. Translation of the neurotransmitterreceptor interaction into an intracellular

signal,
2. Anchoring of and trafficking neurotransmitter receptors to the plasma
membrane,
3. Anchoring various proteins that modulate receptor activity



91. Describe the steps of neurotransmitter vesicle traffic
1. Trafficking to the synapse by kinesins
2. Transmitter Loading happens at synaptic site!
-

an active processes requiring a specific neurotransmitter transporter and a

vacuolar-type proton pump ATPase

3. Docking dependent on small GTPases

4. Fusion to presynaptic membrane
-

Ca-dependant, by activation of synaptogamins

Incomplete: kiss and run

Complete: exocitosis

5. Endocytosis or..

Clathrin-depenedent

6. Neurotransmitter clearance
-

Reuptake in the presynaptic compartment by membrane transporters

(dopamine)

Metabolization in the synaptic cleft (acetylcholine)

92. The Schwann cell

Origin: Neural crest cell

Two phenotypes:
- Myelinizing type- express myelin markers (e.g. MBPs; myelin basic proteins,
glycoprotein PO)
- Non-myelinizing type

In the PNS, Schwann cells produce the myelin sheath
- The myelin sheath isolates the axon from the surrounding extracellular
compartment of endoneurium.
- Its presence ensures the rapid conduction of nerve impulses.

Function:
1. The main function of Schwann cells is to support myelinated and
unmyelinated nerve cell fibers
- The axon hillock and the terminal arborisations where the axon synapses
with its target cells are not covered by myelin

2. Unmyelinated fibers are also enveloped and nurtured by Schwann cell
cytoplasm.

3. Schwann cells aid in cleaning up PNS debris

4. Guide the regrowth of PNS axons.



Formation of myelin sheath;

Myelination begins when a Schwann cell surrounds the axon and its cell membrane
becomes polarized.
During formation of the myelin sheath (also called myelination), the axon initially
lies in a groove on the surface of the Schwann cell (picture below).
- A 0.08- to 0.1-mm segment of the axon then becomes enclosed within each
Schwann cell that lies along the axon.

The Schwann cell surface becomes polarized into two functionally distinct
membrane domains.
- The part of the Schwann cell membrane that is exposed to the external
environment or endoneurium, the abaxonal plasma membrane, represents
one domain.
- The other domain is represented by the adaxonal or periaxonal plasma
membrane, which is in direct contact with the axon.

When the axon is completely enclosed by the Schwann cell membrane, a third
domain, the mesaxon, is created

This third domain is a double membrane that connects the abaxonal and
adaxonal membranes and encloses the narrow extracellular space.




93. The myelin sheath

Definition:
Whitish, fatty, segmented sheath around most long axons

Functions:
- Protects the axon
- Electrically insulates fibers from one another
- Increases the speed of nerve impulse transmission
- Produced by supportive cells:
Oligodendrocyte in CNS
Schwann cell in PNS

Formation:
In the CNS;
- The myelin sheath is formed by concentric layers of oligodendrocyte plasma
membrane
In the PNS;
- The myelin sheath develops from compacted layers of Schwann cell
mesaxon wrapped concentrically around the axon.
- Myelination begins when a Schwann cell surrounds the axon and its cell
membrane becomes polarized.

Summary:

94. Neurogenesis in adult life; neural stem cells

Neurogenesis is the generation of new neurons in adult life; this takes
place in the dentage gyrus of hippocampus. The new neurons are
generated from neural stem and progenitor cells. This process is most
active during pre-natal development, its also responsible for populating
the growing brain with neurons. New neurons are continually born
throughout adulthood in predominantly two regions of the brain, the
subventricular zone (SVZ) and subgranular zone (SGZ). Many of the
newborn cells die shortly after the are born, however a number of them
become functionally integrated into the surrounding brain tissue.
Modulation of adult neurogenesis:
1. Inhibitory influences such as:
Ageing
Stress
Cortisol
Alcohol
2. Enhancement effect:
- Learning
- Ovarian hormones
- Dopamine
- Growth factors (EGF, IGF-I)
- Physical exercise
Potential therapeutical use of neurogenesis for certain diseases:
- Huntington - Parkinson
- Depression - Alzheimer
- Stroke
- Stem cell therapy
- Growth factor therapy
- Fetal brain transplant
Neural stem cells:
- Undifferentiated (Nestin positive)
- Multipotent
- Self renewal capability
- Highly mobile in pathological circumstances.
Neural stem cells differentiate into neurons, astrocytes and
oligodendrocytes. The neural stem cell niche is formed by astroglia,
mircroglia and endothelial cells. Populated with renewal cells,
intermediate progenitors (mitotically active) and neuroblasts.

95. The Choroidal plexus: structure, ultrastructure, physiological

role
The choroid plexus is a highly specialized tissue that projects as elaborate
folds with many villi into the four large ventricles of the brain. It is found
in the roofs of the third and fourth ventricles and in parts of the walls of
the two lateral ventricles, all regions in which the ependymal lining
directly contacts the pia mater.
Structure:
The ependymal cells:
Cuboidal, epithelial like cells
Polarised cells
- Apical membrane (numerous micrvilli
- Basolateral membrane (many foldings).
Capillaries:
Non continuous and have gaps between the capillary endothelial cells
allowing the free movement of small molecules.
Ultrastructure:
The choroid ependyma cells contain abundant mitochondria, endoplasmic
reticulum membranes and a prominent Golgi apparatus.
Role:
The main function of the choroid plexus is to remove water from blood
and release it as cerebrospinal fluid (CSF). This fluid completely fills the
ventricles, the central canal of the spinal cord, the subarachnoid space,
and the perivascular spaces. It is important for metabolism within the
CNS and acts to absorb mechanical shocks.
CSF is clear, has a low density, contains Na+, K+ , and Cl ions but very
little protein, and its only cells are normally very sparse lymphocytes. It
is produced continuously across the walls of the choroid plexus villi and
circulates through the ventricles and central canal, from which it passes
into the subarachnoid space. There, arachnoid villi provide the main
pathway for absorption of CSF into the venous circulation since there are
no lymphatic vessels in CNS tissue.

96. Structure of meninges: dura matter, arachnoid and piamatter.

The meninges is a connective tissue that consists of three layers: the dura
mater, arachnoid mater, and pia mater
Dura Mater
The dura mater is the thick external layer consisting of dense, fibroelastic
connective tissue continuous with the periosteum of the skull. Around the
spinal cord the dura mater is separated from the periosteum of the
vertebrae by the epidural space, which contains a plexus of thin-walled
veins and areolar connective tissue.
The dura mater is always separated from the arachnoid by the thin
subdural space. The internal surface of all dura mater, as well as its
external surface in the spinal cord, is covered by simple squamous
epithelium of mesenchymal origin.
Arachnoid
Has two components: (1) a sheet of connective tissue in contact with the
dura mater and (2) a system of loosely arranged trabeculae containing
fibroblasts and collagen. This trabecular system is continuous with the
deeper pia mater. Surrounding the trabeculae is a large, sponge-like
cavity, the subarachnoid space, filled with CSF. This space forms a
hydraulic cushion that protects the CNS from trauma. The subarachnoid
space communicates with the ventricles of the brain.
The connective tissue of the arachnoid is said to be avascular because it
lacks nutritive capillaries, but larger blood vessels run through it. Because
the arachnoid has fewer trabeculae in the spinal cord, it can be more
clearly distinguished from the pia mater in that area. The arachnoid and
the pia mater are intimately associated and are often considered a single
membrane called the pia-arachnoid.
In some areas, the arachnoid perforates the dura mater and protrudes into
blood-filled venous sinuses within the dura mater. These CSF-filled
protrusions, which are covered by vascular endothelial cells, are called
arachnoid villi. Their function is to transport CSF from the subarachnoid
space into venous sinuses.

Pia Mater
The innermost pia mater is lined internally by flattened, mesenchymally
derived cells closely applied to the entire surface of the CNS tissue, but
this layer does not directly contact nerve cells or fibers. Between the pia
mater and the neural elements is a thin limiting layer of astrocytic
processes, which adheres firmly to the pia mater. Together the pia mater
and glial layer form a physical barrier at the CNS periphery. This barrier
separates the CNS tissue from the CSF in the subarachnoid space.
Blood vessels penetrate the CNS through tunnels covered by pia mater
the perivascular spaces. The pia mater disappears when the blood vessels
branch to the smallest capillaries. However, these capillaries remain
completely covered by expanded perivascular processes of astrocytes.

97. Histologic organization of peripheral nerves

A peripheral nerve is composed of numerous axons of various sizes that
are surrounded by sev- eral layers of connective tissue, which partition
the nerve into several nerve (axon) bundles or fas- cicles. The outermost
connective tissue layer is the strong sheath epineurium that binds all
fasci- cles together. It consists of dense irregular connective tissue that
completely surrounds the peripheral nerve. A thinner connective tissue
layer called the perineurium extends into the nerve and surrounds one or
more individual nerve fascicles. Within each fascicle are individual axons
and their supporting cells, the Schwann cells. Each myelinated axon or a
cluster of unmyelinated axons associated with a Schwann cell is
surrounded by a loose vascular connective tissue layer of thin reticular
fibers, called the endoneurium.
Nuclei seen between individual axons are Schwann cells and fibrocytes
Schwann cells myelinate and surround individual axons, or enclose
unmyelinated axons
Between individual Schwann cells in myelinated axons are the nodes of
Ranvier
Conduction along myelinated axon is called saltatory conduction
Small satellite cells surround neurons of PNS ganglia
Satellite cells provide structural support, insulate, and regulate
metabolic exchanges

98. Histologic organization of ganglia

Are ovoid structures that are surrounded by connective tissue. They could
be Intramural, craniospinal or autonomic. Ganglia (singular, ganglion) are
small accumulations of neurons and supportive glial cells surrounded by
a connective tissue capsule. The nerves of the PNS contain both sensory
and motor axons. These axons transmit information between the
peripheral organs and the CNS. The neurons of the peripheral nerves are
located either within the CNS or outside of the CNS in different ganglia.
Dorsal root (Spinal) ganglia:
Sensitive
On the dorsal roots of the spinal nerves
Medullar zone: mostly myelinated nerve fibres
The neuron cell bodies belong to large, pseudounipolar sensory neurons
that have a single T-shaped process; these are the afferent fibers
carrying sensory information from the periphery (sensory receptors in the
skin, joints and muscles that respond to touch, temperature, pain, stretch)
to the dorsal horn, where they synapse on neurons in the spinal cord.
Autonomic ganglia:
Autonomic ganglia contain cell bodies of sympathetic or parasympathetic
motor neurons, which receive synaptic input from preganglionic
autonomic neurons whose cell bodies are located in the CNS. The
autonomic motor neurons in the ganglia send efferent fibers
(postganglionic autonomic nerve fibers) to innervate cardiac muscle
fibers of the heart and smooth muscle fibers of body organs and glands.
Sympathetic:
The cell bodies of sympathetic neurons are smaller than those of sensory
neurons in the dorsal root ganglion, and often have eccentrically placed
nuclei. The cell profile appears somewhat angular, since these cells are
multipolar, and the roots of their processes are often included in the plane
of section. The satellite cells (glial cells) are sparse and less apparent.
Parasympathetic:
Parasympathetic ganglia are located in the organ that is being innervated.

99. The blood-brain barrier.

The blood-brain barrier (BBB) is a functional barrier that allows much
tighter control than that in most tissues over the passage of substances
moving from blood into the CNS tissue, protecting the nature of the
neuronal microenvironment. The main structural component of the BBB
is the capillary endothelium, in which the cells are tightly sealed together
with well-developed occluding junctions and show little or no
transcytosis. Moreover, the basal lamina of capillaries in most CNS
regions is enveloped by the perivascular feet of astrocytes, which further
regulate passage of molecules and ions from blood to brain.
The BBB allows the stable composition and constant balance of ions in
the interstitial fluid surrounding neurons and glial cells that is required for
their function and protects these cells from potential toxins and infectious
agents. The components of the BBB are not found in the choroid plexus
where CSF is produced, in the posterior pituitary, which releases
hormones, or in regions of the hypothalamus where plasma components
are monitored.
The circumventricular organs: These nuclei are located along the
ventricles and are unique in the brain in that they lack a BBB. This allows
them to monitor substances in the blood that would normally be shielded
from neural tissue.

100. General histological organization of central nervous system

organs: spinal cord, cerebral hemispheres, cerebellum.
It has virtually no connective tissue and is therefore a relatively soft, gellike organ.
The central nervous system consists of the brain located in the cranial
cavity and the spinal cord located in the vertebral canal. The CNS is
protected by the skull and vertebrae and is surrounded by three
connective tissue membranes called meninges. The brain and spinal cord
essentially float in the cerebrospinal fluid that occupies the space between
the two inner meningeal layers. The brain is further subdivided into the
cerebrum, cerebellum, and brain stem that connect with the spinal cord.
Spinal cord:
The spinal cord is the most caudal portion of the CNS, extending from
the base of the skull to the first lumbar vertebra. The spinal cord is
segmented, with 31 pairs of spinal nerves that contain both sensory
(afferent) nerves and motor (efferent) nerves.
It is divided into 31 segments (8 cervical, 12 thoracic, 5 lumbar, 5 sacral,
and 1 coccygeal), and each segment is connected to a pair of spinal
nerves. Each spinal nerve is joined to its segment of the cord by a number
of rootlets grouped as dorsal (posterior) or ventral (anterior) roots. In
cross-section, the spinal cord exhibits a butterfly-shaped grayish-tan inner
substance surrounding the central canal, the gray matter, and a whitish
peripheral substance, the white matter.
Cerebellum:
The cerebellar cortex, which coordinates muscular activity throughout the
body, has three layers, an outer molecular layer, a central layer of very
large neurons called Purkinje cells, and an inner granule layer. The
Purkinje cell bodies are conspicuous even in H&E stained material and
their dendrites extend throughout the molecular layer as a branching
basket of nerve fibers. The granule layer is formed by very small neurons
(the smallest in the body), which are packed together densely, in contrast
to the neuronal cell bodies in the molecular layer which are sparse.
Cerebral Hemispheres:
Brain has 2 hemispheres ( left and right)
Corpus collosum is major pathway between the two.

Cerebrum has 6 layers:

1. Molecular layer: homogenous aspect with few small neurons
2. External granular layer: small granular cells
3. External pyramidal layer: thickest layer in the section
4. Internal granular layer: small and few large granule cells
5. Internal pyramidal layer: Large pyramidal neurons
6. Polymorph layer: Cells of various shapes many of which are
fusiform.