CARTILAGE
Mar 22, 2016
CARTILAGE
Features & Functions
The extracellular substance is rich in proteoglycans and gycosaminoglycans
Avascular
Acts as shock absorber
Surrounded by perichondrium Except: ….
It supports soft tissue
It facilitates movement of the bone
It is essential for bone development and growth
Components of Cartilage
Perichondrium
Outer fibrous
Inner cellular
Cells
Chondroblasts
Chondrocytes
Fibres
Collagen
Elastic
Ground Substance
Proteoglycans
Glycosaminoglycans
Perichondrium: present in all types of
cartilage except fibrous and articular cartilages.
Outer fibrous: dense regular connective
tissue, fibroblasts and type I collagen fibres.
Inner cellular: contains undifferentiated cells
(chondrogenic), essential for growth.
Cells of cartilage:
Chondroblasts: situated under the perichondrium, originate
from mesenchymal cell, typical protein synthesizing cells.
Chondrocytes: situated in lacuna, elliptical shape, axis parallel to the
perichondrium. Usually seen in isogenous groups.
Lacuna= space occupied by chondrocyte.
Isogenous group= cells originating from the
mitotic activity of one chondrocyte.
Types of cartilage
Hyaline Elastic Fibrous
Distribution of hyaline cartilage
Epiphyseal growth plate
Costal cartilage
Thyroid cartilage
Fetal skeleton
Nose
Trachea and bronchi
Hyaline Cartilage
Distribution of elastic cartilage
Ear pinna
External auditory tube
Eustachian tube
Epiglottis
Growth of Cartilage
Interstitial growth
Appositional growth
Clinical Problems
Tumors
Chondroma
Chondrosarcoma
Degenerative changes
Herniation of the intervertebral disc
Herniated Disc
The Cell Cycle
Stages of the Cell Cycle
Interphase
Primary growth phase (G1)
Synthesis phase (S)
Secondary growth phase (G2)
Mitosis
Prophase
Metaphase
Anaphase
Telophase
Cytokinesis
Interphase
DNA replicated
Organelles replicated
Cell increases in size
cells spend most of their time in this intermediate non-mitotic state
G1 - Interphase
The time gap between mitosis and RNA replication.
There is active synthesis of RNA and proteins.
Cellular content excluding chromosomes is duplicated.
Cell size grows to the original size.
S - Interphase
Beginning of centrosome duplication.
Synthesis of DNA and histones.
G2 - Interphase
Accumulation of proteins needed for mitosis.
Replicated chromosomes become loosely coiled.
Followed by mitosis (M phase).
Control of the cell cycle
Mitosis
Prophase …1
Chromatin begins to coil and condense to form chromosomes
Each chromosome appears to have two strands (each containing a single molecule of DNA), each strand is called a chromatid
Each chromatid is attached to its sister chromatid at the centromere
At this stage, the number of chromosomes (containing a pair of chromatids) is considered to be equal to the number of centromeres .the two chromatids are the result of DNA replication that takes place just before mitosis starts.
Prophase …2
the two chromatids are the result of DNA replication that takes place just before mitosis starts.
the nuclear envelope disappears
the nucleolus disappears
in cytoplasm, the spindle apparatus forms
eventually the spindle guides the separation of sister chromatids into the two daughter cells
Metaphase
spindle grows and forms attachments to the chromosomes at the centromeres
chromosomes move to an equatorial plate (metaphase plate) which is formed along the midline of the cell between the poles
chromosomes are at their most condensed state now
metaphase chromosomes can be stained and will show distinctive banding patterns
Anaphase
centromeres divide to create two chromosomes instead of a pair of attached chromatids
spindle fibers shorten and the sister chromosomes are drawn to the opposite poles of the cell
poles of the spindle apparatus are pushed apart as the cell elongates
anaphase results in the exact division of chromosome, distributing one complete diploid complement of genetic information to each daughter cell
Telophase
nuclear envelopes reassemble and surround each set of daughter chromosomes
nucleoli reappear inside the newly formed nuclei
in animal cell, a furrow appears around the cell that eventually pinches the cell into two new cells
in plants, a cell plate forms between the two daughter nuclei as the cell wall divides the cell
chromosomes decondense in the daughter cells to become chromatin and the cells are once again in Interphase
Meiosis
Mitosis
Cells produced have the haploid number of chromosomes.
Synapsis = homologous chromosomes of each pair are associated along their length.
• Crossovers occur during the synapsis process, resulting in new combinations.
Chromosomes of cells entering meiosis contain the two identical copies of sister chromatids.
Unique Features of Meiosis
At the start of prophase I, the chromosomes have already duplicated. During prophase I, they coil and become shorter and thicker and visible under the light microscope.
The duplicated homologous chromosomes pair, and crossing-over occurs. At this point, each homologous chromosome pair is visible as a bivalent (tetrad
The nucleolus disappears during prophase I.
In the cytoplasm, the meiotic spindle, consisting of microtubules and other proteins, forms between the two pairs of centrioles as they migrate to opposite poles of the cell.
The nuclear envelope disappears at the end of prophase I, allowing the spindle to enter the nucleus.
Prophase I is the longest phase of meiosis, typically consuming 90% of the time for the two divisions.
Prophase I
Metaphase I
The centrioles are at opposite poles of the cell.
The pairs of homologous chromosomes (the bivalents), now as tightly coiled and condensed as they will be in meiosis, become arranged on a plane equidistant from the poles called the metaphase plate.
Spindle fibers from one pole of the cell attach to one chromosome of each pair (seen as sister chromatids), and spindle fibers from the opposite pole attach to the homologous chromosome (again, seen as sister chromatids).
Anaphase I
Anaphase I begins when the two chromosomes of each bivalent (tetrad) separate and start moving toward opposite poles of the cell as a result of the action of the spindle.
In anaphase I the sister chromatids remain attached at their centromeres and move together toward the poles. A key difference between mitosis and meiosis is that sister chromatids remain joined after metaphase in meiosis I, whereas in mitosis they separate.
Telophase I and Interkinesis The homologous chromosome pairs complete
their migration to the two poles as a result of the action of the spindle. Now a haploid set of chromosomes is at each pole, with each chromosome still having two chromatids.
A nuclear envelope reforms around each chromosome set, the spindle disappears, and cytokinesis follows. In animal cells, cytokinesis involves the formation of a cleavage furrow, resulting in the pinching of the cell into two cells. After cytokinesis, each of the two progeny cells has a nucleus with a haploid set of replicated chromosomes.
Many cells that undergo rapid meiosis do not decondense the chromosomes at the end of telophase I. Other cells do exhibit chromosome decondensation at this time; the chromosomes recondense in prophase II.
Prophase II While chromosome duplication took place prior to meiosis I, no new chromosome replication occurs before meiosis II.
The centrioles duplicate. This occurs by separation of the two members of the pair, and then the formation of a daughter centriole perpendicular to each original centriole. The two pairs of centrioles separate into two centrosomes.
The nuclear envelope breaks down, and the spindle apparatus forms.
Metaphase II
Each of the daughter cells completes the formation of a spindle apparatus.
Single chromosomes align on the metaphase plate, much as chromosomes do in mitosis. This is in contrast to metaphase I, in which homologous pairs of chromosomes align on the metaphase plate.
For each chromosome, the kinetochores of the sister chromatids face the opposite poles, and each is attached to a kinetochore microtubule coming from that pole.
Anaphase II
Centromeres of sister chromatids are detached from each other.
The now non-replicated chromosomes are pulled to the poles of the cells.
Telophase II and Cytokinesis
Each new nucleus formed has half the number of the original chromosomes but each nucleus has one of each type of homologous chromosome.
A total of four new cells will be produced.
Stages of Meiosis
Connective Tissue
1
General Features
Originates from the mesenchyme.
Composed of cells, fibres and extracellular matrix.
Highly vascular.
Variable regenerative power.
2
Functions of Connective Tissue
Support:
Defense and protection:
Storage:
Medium for exchange:
3
Cells of the Connective
Tissue
4
Fixed cells:
• Fibroblasts.
• Adipose cells.
• Pericytes.
• Mast cells.
• Macrophages.
Transient cells:
• Plasma cells.
• White blood cells (Neutrophils, Eosinophils, Basophils, Lymphocytes, Monocytes).
• Macrophages.
5
Fibroblast
6
Fibroblasts
The most numerous cells of connective tissue.
Occur in active and inactive forms (fibrocyte).
Originate from undifferentiated mesenchymal cells.
Capable of some movement.
Rarely undergo division.
FGF may influence cell growth and differentiation.
7
Active fibroblasts
Closely associated with collagen bundles.
Elongated, fusiform, and have many processes.
Cytoplasm is pale and difficult to be differentiated from near by tissue.
Nucleus is large, dark stained and granular.
E.M: prominent Golgi, mitochondria, rER, actin and myosin.
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9
Inactive Fibroblast (Fibrocyte)
Smaller and ovoid with acidophylic cytoplasm.
The nucleus is smaller and darker.
Few processes.
E.M: few rER and many ribosomes.
When stimulated, it may revert to fibroblast.
10
11
Myofibroblast
Has features of both smooth muscles and fibroblasts.
Their contraction is responsible for wound contraction.
12
Mast Cell
13
Mast Cell
Large cell ~ 20-30 m.
Derived from precursors in the bone marrow.
Nucleus: central ovoid.
Cytoplasm highly granular, metachromatic.
Grnules contain:
• Heparin
• Histamin
• Leukotriens
• Eosinophil chemotactic factor.
• Neutrophil chemotactic factor.
• Platelet activating factor.
• Bradykinin.
• Thromboxane A2
14
Plasma Cell
Derived from B lymphocytes following exposure to an antigen.
Present at portal of entry of organisms and sites of chronic inflammation.
Life span ~ 2-4 weeks.
Large ovoid cells ~ 20 m.
Nucleus: eccentric with clusters of heterochromatin cart-wheel or clock-face nucleus.
15
Plasma Cell
Cytoplasm:
• Intensely basophilic.
• Well developed supranuclear Golgi apparatus (- ve image).
• Well developed rER.
Functions: secretion of specific antibodies.
16
Macrophage
Derived from monocyte.
Large cells ~15-30 m.
Surface shows many projections.
Nucleus: eccentric, ovoid, dark, and indented (kidney-shaped).
Cytoplasm: basophilic, well developed Golgi, prominent rER, many lysosomes.
They are part of the MPS.
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Pericyte
Derived from undifferentiated mesenchymal cell.
Surrounded by its own basal lamina.
Commonly seen in the walls of capillaries and venules.
They may differentiate into other cells.
18
Extracellular Matrix
Extracellular Matrix = ground substance + fibres.
• Resists compression and stretching forces.
• The water content allows rapid exchange of metabolites.
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Ground Substance
20
Ground Substance
Composed of:
• Glycosaminoglycans:
• Sulfated: keratan sulfate, chondroitin sulfate, dermatan sulfate and heparin.
• Non-sulfated: hylauronic acid
• Proteoglycans:Responsible for the gel state of the extracellular matrix.
• Adhesive glycoproteins: laminin, chondronectin, osteonectin and fibronectin.
21
Types of GAGs
Distribution GAG
Most connective tissue, cartilage,
dermis, synovial fluid. Hyaluronic acid
Cartilage, cornea, intervertebral disc. Keratan sulfate
Blood vessels, lung, basal lamina Heparan sulfate
Cartilage, bone, blood vessels Chondroitin 4-sulfate
Cartilage, blood vessels, umbilical
cord. Chondroitin 6-sulfate
Skin, heart valves, blood vessels Dermatan sulfate
Mast cell granules, basophils, liver
lung, skin. Heparin
22
Functions of Proteoglycans
Resistance of compression.
Retardation of movement of microorganisms.
Act as a filter.
Possess binding sites for growth factors.
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* Connective Tissue Fibres
Collagen
Elastic
Reticular
24
Connective Tissue Fibres
Fibre Properties
Collagen Undulating course of longitudinally striated bundles,
form meshwork of variable texture, stain pink-red in
H&E. Nonextensible.
Elastic Forms sheets or lamina, Unstained in H & E.
Reversibly extinsible. Stains brown-black in Orcein
or Resorscin Fuchsin.
Reticular Delicate network, Unstained in H & E. Reversibly
extinsible. PAS +ve, stains black in AgNO3
(Argyrophilic).
25
Collagen Fibers
Gives the extracellular matrix strength to resist tensile forces.
Formed of protein collagen (20% of all proteins of the body).
H & E: long, wavy pink bundles.
E.M: cross banding at 67 nm.
Fibres are formed of aggregation of fibrils.
Fibrils are formed of tropocollagen.
Tropocollagen is formed of 3 helical polypeptide chains.
26
Collagen bundle
Fibres
Fibrils
Tropocollagen
3 Helical polypeptide chains, α-chains. 27
28
α-chains possess 1000 amino acids.
Every 3rd amino acid is glycine.
• Other amino acids: proline, hydroxyproline, hydroxylysine.
The sequence of aminoacids determines the type of collagen.
• There are 16 types of collagen.
29
Location Function Synthesizing cell Type
Dermis, tendons,
ligament, capsules,
bone, dentin,
cementum
Resist tension Fibroblast, osteoblast,
odontoblast, cementoblast
I
Hyaline and elastic
cartilage
Resists pressure chondroblasts II
Reticuloendothelia
l system, lung, skin
Form structural
framework of
organs
Fibroblasts, reticular cells,
smooth muscle,
hepatocytes
III
Basal lamina Meshwork of the
lamina densa
Epithelium, muscle,
Schwann cells
IV
As in type I and
placenta
Associated with
type I.
Fibroblasts, mesenchymal
cells
V
Derma-epidermal
junction
Anchoring fibrils
between the lamina
densa and reticularis
Epidermal cells VII
Major Types of Collagen
30
EXTRA CELLULAR
Cleavage and assembly
Intracellular * Transcription (Nucleus).
* Translation (rER).
* Hydroxylation (rER).
* Glycosylation (rER & Golgi).
* Formation of the triple helix.
* Secretion of procollagen (trans Golgi network
and microtubules).
*** Vit. C is essential
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32
Clinical Notes:
Progressive Systemic Sclerosis
Keloid
Vitamin C deficiency (Scurvy)
33
Elastic Fibers
• Oxytalan: found in the zonule of the eye and upper dermis.
• Not elastic, highly resistant to pulling forces.
• Elaunin: found in deep dermis around sweat glands
• Elastic:
• Elasticity is due to elastin.
• Elastin = glycine + proline + lysine.
• Stability is due to microfibrils (resistant to boiling).
• Digested by pancreatic enzyme elastase
Composed of:
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Reticular Fibres
Consist mainly type III collagen.
Short, thin and branching.
Give PAS +ve reaction.
Stain with Silver Nitrate (Argyrophylic).
Found mainly in RES organs, endometrium and around blood vessels.
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Edema الوذمــة
37
Edema = increase in the intercellular fluid.
• Arterial:
• Venous:
• Lymphatic: Causes:
38
Forces acting on water in capillaris:
Hydrostatic pressure: favors filtration at the
arterial side of the capillary.
Oncotic pressure: favors absorption at the
venous side of the capillary.
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Classification of Connective Tissue
Connective tissue proper: Loose (areolar): mesentery
Dense regular: tendons and ligaments
Dense irregular: dermis, capsules.
Special connective tissue: Elastic
Reticular
Adipose
Bone
Cartilage
Blood
Embryonic connective tissue: Mesenchymal connective tissue
Mucous connective tissue
41
Epithelium
Features and classification of epithelium were discussed in the practical class.
Discipline is the bridge between goals and accomplishments.
anonymous
The epithelial cell
Shown to have the following domains:
• Apical
• Baso-lateral
Each domain shows modifications to suit its functions.
Apical Domain
It is the part of the cell that faces the lumen (the free surface of the cell).
It is rich in ion channels, carrier proteins and hydrolytic enzymes.
The apical modifications are:
• Microvilli.
• Stereocilia.
• Cilia.
• Flagella.
Microvilli
Present mainly in absorptive cells.
Their number and size vary according to the degree of activity of the cell.
They are usually crowded on the cell apex forming the striate border in the intestine and the brush border in the kidney.
Structure of the Microvillus
The microvillus is 1- 2µ in length.
Contains a core of 25-30 actin filaments.
Actin filaments are cross-linked with villin.
The actin filaments are inserted into the terminal web.
The terminal web is a network of actin and spectrin supported by myosin, IF, and camodulin in the apical part of the cell.
The microvillus is covered by glcocalyx; it gives PAS +ve reaction
Stereocilia are long immotile microvilli present in the
epididymis and inner ear. They have special functions in these
places.
Cilia
Motile cytoplasmic hair like projections capable of moving fluid and particles along epithelial surfaces.
Measurements: length 7-10μ, diameter 0.2 μ.
Number of cilia/cell is variable and ranges 1-300 cilium/cell.
They move rhythmically and rapidly in one direction.
The core of the cilium is called axoneme.
The axoneme consists of longitudinal microtubules arranged as 9 (doublets) peripheral surrounding 2 (singlets) central (9+2).
The singlets are separated by 13 protofilaments.
The doublets are composed of 2 subunits A & B.
Subunit A is formed of 13 protofilaments.
Subunit B is formed of 10 protofilaments.
Neighboring doublets are connected by nexin.
Doublets are connected to the singlets by radial spokes.
Dynein radiates form subunit A to subunit B.
Dynein has ATPase activity.
Cilia are attached to basal bodies similar in structure to centrioles.
Baso-Lateral Domain
Terminal bars are light microscopic structures at the site of contact of cells.
E.M revealed that the terminal bar is a junctional complex composed of:
• Occluding junctions.
• Anchoring junctions.
• Communicating junctions.
Cell Junctions
Anchoring (Desmosomes and Macula adherentes) - mediate cell-cell and cell-matrix adhesions; linked to cytoskeleton to transmit and distribute stress
Occluding (Zonula Ocludentes) - form seals between epithelial cells; block or regulate (paracellular) permeability between cells
Channel-forming (Gap Junction) - allow diffusion of small molecules
Tight Junctions
Occluding junction (encircles epithelial cells)
Barrier to diffusion between cells (paracellular pathway)
Separates apical and basolateral plasma membranes, the outer layers of 2 adjacent plasmalemma fuse together.
Tight Junctions
Tight junction blocks diffusion of soluble tracer molecules added to either the apical or basolateral compartment.
MBoC5 Fig 19-24
Tight Junction
TEM: is the most apical junction
Freeze fracture of TJ reveals ridges in membranes that correspond to sites of contact between cells
Ridges are linear arrays of occludin and claudin proteins
Tight Junction Permeability
Some claudins and occludins have pores (A, B, and C) that allow selective (paracellular) movement of ions or solutes
Side view Top view
Tight Junction Proteins
Occludins and claudins are transmembrane proteins that interact across the intercellular space to form TJs
ZO (zonula occludens) proteins 1-3 link occludin and claudin to each other, to JAMs, and to actin filaments
Zonula Adherens
Anchoring junction (encircles the cell)
AKA adhesion belt, belt junction, or belt desmosome
Located "under" tight junction in epithelial cells
Connected to actin microfilaments that join terminal web
Zonula Adherens
Cadherin proteins attach to crosslinked actin filaments
Mechanical support - ZA and actin filaments transmit and distribute stress throughout cell and to neighboring cells
Desmosomes
Anchoring junctions
Function as "spot welds" to join cells
Located along lateral plasma membranes of columnar epithelial cells or on processes of squamous cells
Intermediate filaments associate with plaque proteins in cytoplasm
Desmosomes
Desmosomes
cadherins interact across intercellular space
Adaptor proteins form a dense plaque that interconnects cadherins and binds them to intermediate filaments
Desmosomes
Desmoglein and desmocollin are non-classical cadherins
Adaptor proteins such as -catenin (plakoglobin) and desmoplakin link cadherins to intermediate filaments
MBoC5 Fig 19-17
Gap Junction
Channel-forming junction
Named for gap of regular width between cells visualized by TEM
Water-filled junctions transport molecules <1 kDal such as ions, nucleotides (including cAMP), and metabolites
Ross Fig 5-17
Connexin - protein subunit, six form a hexameric connexon
Connexons - two align to form the gap junction channel
Regulation - elevated calcium concentrations close channel
Gap Junction
Hemidesmosomes
Hemidesmosome - "half-desmosome" in appearance only
Mediates attachment to basal lamina (extracellular matrix)
Cytoplasmic plaque is attached to cytoskeletal elements
Hemidesmosomes
Integrins - membrane protein that "integrates" cell into matrix
Integrins
Mediate calcium-independent cell-matrix adhesion
Function as dimers of two membrane proteins ( and )
Adaptor proteins link integrins to intermediate filaments in hemidesmosomes or actin filaments in focal adhesions
Integrins bind matrix proteins such as laminin or fibronectin
Focal Adhesions
Anchoring junction (AKA actin-linked cell-matrix adhesion)
Growing fibroblasts form many focal adhesions (orange) that serve as anchoring points for actin filaments (green)
Focal Adhesions
Fibroblasts attach to extracellular matrix via focal adhesions
Integrins - membrane proteins link actin filaments and matrix
Blistering Disease
Many mechanisms underlie blistering disorders of the skin
Pemphigus group - autoimmune disease in which autoantibodies target desmogleins present in desmosomes
Pemphigus Histology
Acantholysis - separation of epidermal keratinocytes (H&E)
Basal Laminae & Basement Membrane
Basal Lamina
Only visible with E.M
Found also in other tissues
Components are secreted by epithelium, connective tissue, muscle, Schwann cell
Layers of Basal Lamina
Layers of the Basal Lamina
• Lamina Lucida
• Lamina Densa
Lamina Reticularis: not part of the basal lamina
Molecular components are variable but include:
• type IV collagen,
• Glycoproteins (Laminin, entactin…)
• Proteoglycans (Perlecan)
E.M of Basal Lamina
Functions of Basal lamina
Support
Selective barrier
Influencing cell polarity
Regulation of proliferation and growth
Affect cellular metabolism
Affect cell-cell interaction
Clinical Importance of Basal Lamina
Tissue culture
Tumor grading
Glandular
Epithelium
1 Dr. Darwish Badran 2008/2009
Glands are divided into:
Endocrine: • Unicellular: DNES • Multicellular: Thyroid, Adrenal
Exocrine: • Unicellular: Goblet cell • Multicellular: Parotid, Submandibular, Sublingual
Mixed: Liver, Pancreas, Ovary, Testis.
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GLAND DEVELOPMENT I
Mesenchymal-epithelial
exchange of signals
Cell de-differentiation, &
proliferation Epithelium
Mesenchyme
3 Dr. Darwish Badran 2008/2009
GLAND DEVELOPMENT II
Cell de-differentiation,
& proliferation
Epithelial downgrowth
into modified
mesenchyme
Mesenchymal-epithelial exchange of signals
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GLAND DEVELOPMENT III
Differentiation into
duct & secretory cells
Epithelial downgrowth
into modified
mesenchyme
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GLAND DEVELOPMENT IV
Differentiation into
duct & secretory cells
Construction of lumens
Simple alveolar gland
Stroma
6 Dr. Darwish Badran 2008/2009
Although cells in covering and lining epithelia secrete, they are limited
in number. To get more secreting power, and sometimes to focus it
differently, e.g. to interact with blood, rather than dump into a principal
tube, epithelial cells can build glands
GLANDULAR EPITHELIA
ENDOCRINE GLAND
Clumps of endocrine cells
hormone
Duct lined by
cuboidal cells
Secretory unit (acinus or tubule) lined
by “cuboidal” cells
EXOCRINE/DUCTED GLAND
Capillary
basal
lamina
Nerve
control
7 Dr. Darwish Badran 2008/2009
Exocrine Glands.. 1:
Classified according to the mode of secretion:
•Merocrine (eccrine): •Apocrine: •Holocrine:
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secretion released by
exocytosis, with no loss
of cytoplasm
Sebaceous gland
SEBUM
e.g., by endocrine cells
hormone
secretion released,
filling a dead cell
HOLOCRINE
MODES OF SECRETORY RELEASE
MEROCRINE / ECCRINE
released by exocytosis, with
a little loss of cytoplasm
APOCRINE
Female breast 9 Dr. Darwish Badran 2008/2009
Exocrine Glands.. 2:
Classified according to nature of
secretion: • Serous: • Mucous: • Mixed:
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Exocrine Glands.. 3:
Classified according to the duct system and the
secretory part:
Duct:
Simple Compound
Secretory part:
Tubular Acinar
(alveolar) Tubulo-
acinar
11 Dr. Darwish Badran 2008/2009
SIMPLE GLANDS
COMPOUND GLANDS
alveolar
tubular tubulo-alveolar
DUCT tubular alveolar /
acinar
Classification by shape & duct complexity
straight/coiled
12 Dr. Darwish Badran 2008/2009
Glandular Epithelia : Products & Roles
Airway glands, Duodenal & Salivary glands
Extra mucus
Airway glands Extra defense Gastric glands, Pancreas Digestion Liver Blood processing Endocrine glands Hormones Mammary glands Milk
Sweat glands
Sweat
Sebaceous glands
Grease
Special genito-urinary functions Genital glands 13
MUCOUS TUBULE
MYOEPITHELIAL CELL
SEROUS DEMILUNE
BL
SEROUS ALVEOLUS
MUCOUS TUBULE
with
14 Dr. Darwish Badran 2008/2009
muco-ciliary escalator
rids airway of particles
MUCUS-SECRETING
GOBLET CELL
Deliver all along a surface BL
Single cells
exocrine
Deliver all along a surface
Single cells & simple glands
Simple straight tubules,
with - SIMPLE
TUBULAR
Surface goblet cells
Colon cells 15 Dr. Darwish Badran 2008/2009
GUT PARTS
VILLI covered
with simple
columnar
epithelium
MUSCULARIS smooth muscle
SUBMUCOSA
connective tissue
suspensory MESENTERY
with blood vessels
covering SEROSA
with simple
squamous epithelium
GLANDS
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THIN HAIRY SKIN Hair shaft
D
E
R
M
I
S
Epidermis
H
Y
P
O
D
E
R
M
I
S
Large round/ovoid group
of cells, with no duct
SIMPLE ALVEOLAR
Sebaceous gland
SEBUM
17 Dr. Darwish Badran 2008/2009
SWEAT GLAND
Sweat gland
D
E
R
M
I
S
Epidermis
H
Y
P
O
D
E
R
M
I
S
Coiled secretory tubule feeding a coiled thin
wiggly duct - SIMPLE COILED TUBULAR Sweat gland 18 Dr. Darwish Badran 2008/2009
PANCREAS
Duodenum
Exocrine acini
digestive enzymes
Lobule
}
Endocrine islet
metabolic
hormones
Ducts
alkaline ions
Many secretory acini/alveoli feeding branching
duct system - COMPOUND ALVEOLAR
a mixed
exocrine-
endocrine
gland
Deliver at wide intervals
along a surface BL
Large, elaborate, compound
glands
exocrine
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EXOCRINE PANCREAS Ducts 1 Duodenal
papilla Exocrine acini
Lobule
} Principal duct
Interlobular duct
Intralobular ducts
Intercalated ducts 20 Dr. Darwish Badran 2008/2009
Stroma Stroma
Stroma
Traumatic loss of
surface epithelium
Duct Cell de-differentiation,
& proliferation
Stromal cell re-activation, &
proliferation
Restitution of basal lamina &
stroma
Epithelial upgrowth and
outgrowth over clot
Fibrin clot
Differentiation into
surface & duct cells
REGENERATION from
ducts 21 Dr. Darwish Badran 2008/2009
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Unicellular gland
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Unicellular gland
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Simple tubular glands
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Simple coiled tubular gland
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Simple branched tubular
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Simple alveolar glands
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Compound tubular glands
29 Dr. Darwish Badran 2008/2009
Serous gland- parotid
30 Dr. Darwish Badran 2008/2009
Seromucous gland
31 Dr. Darwish Badran 2008/2009
Mucus gland
32 Dr. Darwish Badran 2008/2009
Apocrine gland
33 Dr. Darwish Badran 2008/2009
34 Dr. Darwish Badran 2008/2009
The Nucleus
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Nucleus • The nucleus is a
membrane bound
structure that contains the
cell's hereditary
information and controls
the cell's growth and
reproduction.
• It is commonly the most
prominent organelle in the
cell
Nuclear Envelope
Surrounds the nuclear material.
Consists of two parallel membranes, separated from each other by a narrow perinuclear cisterns.
These membranes fuse at intervals, forming openings in the nuclear envelope called nuclear pores.
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Outer Membrane
The outer membrane 6 nm thick.
It faces the cytoplasm and is continuous at certain sites with the rough endoplasmic reticulum.
A loosely arranged mesh of intermediate filaments (vimentin) surrounds the outer nuclear membrane on its cytoplasmic aspect.
Ribosomes stud the cytoplasmic surface of the outer nuclear membrane.
These ribosomes synthesize proteins that enter the perinuclear cisterna.
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Inner Membrane
6 nm thick.
Faces the nuclear material.
Separated from it and supported on its inner surface by the nuclear lamina, a fibrous lamina that is 80-300 nm thick.
Composed primarily of lamins A, B, and C.
These intermediate filament proteins help organize the nuclear envelope and perinuclear chromatin.
Additionally they are essential during the mitotic events, when they am responsible for the disassembly and reassembly of the nuclear envelope.
Phosphorylation of lamins leads to disassembly, and dephosphorylation results in reassembly of the nuclear envelope.
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Perinuclear cisterns
Located between the inner and outer nuclear membranes and is 20-40 nm wide.
Continuous with the cisternae of the RER.
It is perforated by nuclear pores at various locations.
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Nuclear pores
Average 80 nm in diameter.
Number from dozens to thousands depending upon the metabolic activity; they are associated with: The nuclear pore complex (NPC).
Formed by fusion of the inner and outer nuclear membranes.
Permit passage of certain molecules in either direction between the nucleus and cytoplasm via a 9-nm chamel opening.
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Nuclear pore complex (NPC)
The NPC is composed of nearly 100 proteins, some of which are arranged in eight-fold symmetry around the margin of the pore.
It consists of cytoplasmic ring, nucleoplasmic ring and the middle ring.
The nucleoplasmic side of the pore exhibits a nuclear basket, whereas the cytoplasmic side displays fibers extending into the cytoplasm.
A transporter protein is located in the central core and is believed to be responsible for transporting proteins into and out of the nucleus via receptor-mediated transport.
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Functions of the Nuclear Pore Complex (NPC)
The NPC permits passive movement across the nuclear envelope via a 9- to 11-nm open channel fiber simple diffusion.
Most proteins, regardless of size, pass in either direction only by receptor-mediated transport.
These proteins have clusters of certain amino acids known as nuclear localization segments (NLS) that act as signals for transport.
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Nucleolus
Nuclear inclusion that is not surrounded by a membrane.
It is present in cells that are actively synthesizing proteins;
More than one nucleolus can be present in the nucleus.
It is generally detectable only when the cell is in interphase.
Contains mostly rRNA and protein as well as a modest amount of DNA.
It possesses nucleolar organizer regions (NORs), portions of those chromosomes (in humans, chromosomes 13,14,15,21, and 22) where rRNA genes are located; these regions are involved
in reconstituting the nucleolus during the GI phase of the cell cycle.
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Nucleolus
The nucleolus contains four distinct regions.
• Fibrillar centers are composed of inactive DNA where DNA is not being transcribed.
• Pars fibrosa are composed of 5-nm fibrils surrounding the fibrillar centers and contain transcriptionally active DNA and the rRNA precursors that are being transcribed.
• Pars granulosa are composed of 15-nm maturing ribosomal precursor particles.
• Nucleolar matrix is a fiber network participating in the organization of the nucleolus.
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Nucleolus Functions
Synthesis of rRNA and its assembly into ribosome precursors.
sequesters certain nucleolar proteins that function as cell-cycle checkpoint signaling proteins.
Three such cell-cycle regulator proteins have been identified within the nucleolus, where they remain sequestered until their release is required for targets in the nucleus and/or cytoplasm.
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Nucleoplasm
Nucleoplasm is the protoplasm within the nuclear envelope.
It consists of a nuclear matrix and various types of particles.
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Nuclear matrix
Nuclear matrix acts as a scaffold that aids in organizing the nucleoplasm.
It contains other components:
Structural components include fibrillar elements, nuclear pore, nuclear lamina complex, residual nucleoli, and a residual ribonucleoprotein (RNP) network.
Functional components are involved in the transcription and processing of mRNA and rRNA, steroid receptor-binding sites, carcinogen binding sites, heat-shock proteins, DNA viruses, and viral proteins ('I‘ antigen).
• It may have many more functions which are currently not known. 14
Nuclear Particles
Heterchromatin granules are clusters of irregularly distributed particles
(20-25 nm in diameter) that contain RNP and various enzymes.
Perichromatin granules are single dense granules (30- 50 nm in diameter) surrounded by a less dense halo.
• Located at the periphery of heterochromatin and exhibit a substructure of 3-nm packed fibrils.
• Contain 4.7s RNA and two peptides similar to those found in heterogeneous nuclear RNPs (hnRNPs ).
• They may represent messenger RNPs (mRNPs).
• The number of granules increases in liver cells exposed to carcinogens or temperatures above 37°C.
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Nuclear particles
The hnRNP particles are complexes of precursor mRNA (premRNA) and proteins and are involved in processing of pre-mRNA.
Small nuclear RNPs (snRNPs) are complexes of proteins and small RNAs and are involved in hnRNP splicing or in cleavage reactions.
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Chromatin
Chromatin consists of double-stranded DNA complexed with histones and acidic proteins.
It resides within the nucleus as heterochromatin and euchromatin.
The euchromatin-heterochromatin ratio is higher in malignant cells than in normal cells.
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Chromatin
Heterochromatin is the condensed inactive chromatin, is concentrated at the periphery of the nucleus and around the nucleolus, as well as scattered throughout the nucleoplasm.
Euchromatin is the trascriptionally active form of chromatin that appears in the LM as a lightly stained region of the nucleus.
The main function of chromatin is the synthesis of RNA and cell division.
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Other components of the nucleus
Some of the components which also form a part of the nucleus include the:
• DNA.
• Different classes of RNA (m-RNA, r-RNA and t-RNA).
These are important for cell survival, cell division, and protein synthesis.
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