EPITHELIAL TISSUEEPITHELIAL TISSUE

Membrana basalisMembrana basalis

Membrana basalis: basal lamina, basement membrane Membrana basalis: basal lamina, basement membrane (thin, separating layer beneath the epithelial cells).(thin, separating layer beneath the epithelial cells).

Lamina rara, lamina densa, lamina fibroreticularis.Lamina rara, lamina densa, lamina fibroreticularis. Proteins: laminin, fibronectin, collagen.Proteins: laminin, fibronectin, collagen. Glycosaminoglycans (GAG): long polysaccharide Glycosaminoglycans (GAG): long polysaccharide

chains (hyaluronic acid, heparin, chondroitin sulphate, chains (hyaluronic acid, heparin, chondroitin sulphate, etcetc).).

Proteoglycans: complexes of GAGProteoglycans: complexes of GAGs and proteins.s and proteins. Function of basal lamina: mechanical support of the Function of basal lamina: mechanical support of the

cells (hemidesmosomes); molecular surface on which cells (hemidesmosomes); molecular surface on which cells migrate (regeneration); barrier; molecular sieve cells migrate (regeneration); barrier; molecular sieve (kidney)(kidney)

Detection: routine stains (HE), immunohistochemistry, Detection: routine stains (HE), immunohistochemistry, electron microscopy.electron microscopy.

THE MEMBRANA BASALIS IN THE LIGHT MICROSCOPETHE MEMBRANA BASALIS IN THE LIGHT MICROSCOPE

THE MOLECULAR STRUCTURE OF MEMBRANA BASALIS:THE MOLECULAR STRUCTURE OF MEMBRANA BASALIS:LAMININ RECEPTORS, INTEGRINS AND CADHERINS IN THE CELL LAMININ RECEPTORS, INTEGRINS AND CADHERINS IN THE CELL

BIND TO THE EXTRACELLULAR PROTEINS AND PROTEOGLYCANSBIND TO THE EXTRACELLULAR PROTEINS AND PROTEOGLYCANSPRESENT IN THE MEMBRANA BASALISPRESENT IN THE MEMBRANA BASALIS

SIMPLE SQUAMOUS EPITHELIUM: MESOTHELSIMPLE SQUAMOUS EPITHELIUM: MESOTHEL

SIMPLE SQUAMOUS EPITHELIUM: ENDOTHEL (CONTINUOUS, FENESTRATED)SIMPLE SQUAMOUS EPITHELIUM: ENDOTHEL (CONTINUOUS, FENESTRATED)

STRATIFIED SQUAMOUSSTRATIFIED SQUAMOUSEPITHELIUMEPITHELIUM

STR. PLANOCELLULARESTR. PLANOCELLULARE

STR. SPINOSUM/STR. SPINOSUM/POLYGONALEPOLYGONALE

STR. BASALESTR. BASALE

STRATIFIED SQUAMOUS, KERATINIZINGSTRATIFIED SQUAMOUS, KERATINIZINGEPITHELIUMEPITHELIUM(EPIDERMIS)(EPIDERMIS)

Str. lucidumStr. lucidum

PIGMENTED (MELANIN) KERATINOCYTES IN THEPIGMENTED (MELANIN) KERATINOCYTES IN THEEPIDERMIS (SKIN)EPIDERMIS (SKIN)

SIMPLE CUBOIDAL EPITHELIUMSIMPLE CUBOIDAL EPITHELIUM

SIMPLE COLUMNAR EPITHELIUM SIMPLE COLUMNAR EPITHELIUM (ENTEROCYTES ON THE INTESTINAL MUCOUS MEMBRANE)(ENTEROCYTES ON THE INTESTINAL MUCOUS MEMBRANE)

PSEUDOSTRATIFIED COLUMNAR, CILIATED EPITHELIUMPSEUDOSTRATIFIED COLUMNAR, CILIATED EPITHELIUM

CILIA WITH EMCILIA WITH EM(AXONEME)(AXONEME)

CILIA WITH SCANNING EM (TRACHEA)CILIA WITH SCANNING EM (TRACHEA)

STRATIFIED COLUMNAR EPITHELIUM (URETHRA)STRATIFIED COLUMNAR EPITHELIUM (URETHRA)

TRANSITIONAL EPITHELIUM (UROTHELIUM) TRANSITIONAL EPITHELIUM (UROTHELIUM)

TRANSITION OF DIFFERENT EPITHELIA: CARDIATRANSITION OF DIFFERENT EPITHELIA: CARDIA(SIMPLE COLUMNAR (SIMPLE COLUMNAR STR. SQUAMOUS)STR. SQUAMOUS)

UNICELLULAR GLANDS: GOBLET CELLS IN SIMPLE COLUMNAR EPITHELIUMUNICELLULAR GLANDS: GOBLET CELLS IN SIMPLE COLUMNAR EPITHELIUM

GOBLET CELLGOBLET CELL

BRUSH BORDER ON THE APICAL SURFACE OF CELLSBRUSH BORDER ON THE APICAL SURFACE OF CELLS

MUCOUS GLAND ACINI: SUBLINGUAL GLANDMUCOUS GLAND ACINI: SUBLINGUAL GLAND

EXCRETORY DUCTEXCRETORY DUCT

GLANDULAR ACINIGLANDULAR ACINI

PIGMENT EPITHELIUM: MELANINPIGMENT EPITHELIUM: MELANIN--PRODUCING EPITHELIUM (RETINA)PRODUCING EPITHELIUM (RETINA)(UNSTAINED SPECIMEN)(UNSTAINED SPECIMEN)

Connective tissues

Connective tissue (CT) develops from the mesoderm of the embryo: the paraxial mesoderm gives rise not only to CT, but also

to skeletal elements and muscle.

Neural tube

Paraxial mesoderm

Lateral mes.

Ectoderm

chorda

Introduction

Connective tissue connects, holds and supports other body tissues.

The cells of connective tissue are characteristically separated from one another by large amount of intercellular material.

The extracellular material determines connective tissues quality and strenght.

Components: Cells; Extracellular fibers (collagen, etc); Extracellular matrix (ECM).

Two types of cells are present in the

connective tissue:

FIXED (resident)

Fibroblast

Adipocyte

Melanocyte

Mesoblast

Reticular cell

MOBILE (migrating)

Plasma cell

Mast cell

Histiocyte (macrophage)

Lymphocyte

Granulocyte

Fibroblast,

fibrocyte

Fibroblasts are responsible for the formation of collagen-, elastic- and reticular fibers and the amorphous material (ECM).

The old, nonproductive cells are commonly called fibrocytes.

Fibrocytes can transform into fibroblast by various growth factors (e.g.: interleukin-1, platelet-derived growth factor).

The fibrocytes, and the fibroblasts, are spindle-shaped.

Fibroblasts and collagen fibers (HE and EM)

Fat cells (adipocyte) The types of the adipocyte:

Unilocular adipocytes contain one large droplet of yellow fat in their cytoplasm.

Multilocular adipocytes contain numerous lipid droplets and large number of mitochondria.

Fat cells are scattered throughout the body in connective tissue; when many adipocytes accumulate they form fat tissue (adipose tissue). Unilocular fat cells constitute yellow fattissue, multilocular adipocates form brown fat.

Melanocyte Melanocytes synthesize

the pigment melanin. Melanin is localized in melanosomes.

They are located in the deepest layer of the epidermis, and in the loose connective tissue.

They are responsible for the color of the skin.

In lower vertebrates melanocytes they are regulated by the pituitary gland: melanocyte stimulating hormone (MSH).

Mesoblast-mesenchymal cell

These cells are closely resemble fibroblasts and can give rise to other normal connective tissue cells, such as fat cells or fibroblasts.

They are multipotential like the embryonic mesenchymal cells.

They are important in forming new fibroblasts and may form other cell types, too (regenerationof the connective tissue).

Reticular cells (fibroblast-type)

These cells produce the reticular fibers, located in small external compartments, formed by the reticular cell processes. They are characteristic cells of the lymphoid and hemopoietic tissues (red bone marrow, lymph node).

Reticular fibers

Granulocytes

Neutrophils and eosinophils are present in the connective tissues.

They are phagocytosing and mobile. They migrate from the blood vessels into the CT.

Granulocytes

NEUTROPHILS

EOSINOPHILS

BASOPHILS

The cells were photographed inperipheral blood film

Mast cells

Mast cells

Defensive cells, numerous around blood vessels and nerves.

Granules contain heparin (GAG), histamine, enzymes and chemotactic factors which stimulate granulocytes.

Granules liberate their content following chemical, mechanical and immune stimuli.

Degranulation causes increased vascular permeability, smooth muscle contraction and activation of granulocytes.

Mast cells are produced in the red bone marrow, migrate to connective tissues, where they become resident cells.

We stain them with basic anilin dyes (methylene blue).

Other migrant cells of the CT, (blood film)

LYMPHOCYTES

MONOCYTES (MACROPHAGES)

Histiocytes (macrophages)

Macrophages are mobile cells and are capable of phagocytosing and digesting foreign and other particulate matter.

This capability is evidenced by the numerous vacuoles, lysosomes, and residual bodies in their cytoplasm.They also secrete a number of lysosomal enzymes.

Multinucleated giant cells in chronic inflammations are born from fusion of histiocytes.

Different lymphocytes:- Small lymphocyte (blood)- Plasma cell (CT)- Lymphoblast (blood)

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Extracellular space

Fibers

Collagen fibers

Elastic fibers

Reticular fibers

Amorphous material

(ECM)

GAG and proteoglycans

Fibronectin, laminin

Tissue fluid: water and solublemolecules (small, large)

Collagen fibers

Collagen fibers are composed of the protein collagen.

They have great tensile strength and are non-elastic.

The fibers measure between 1-10 m in thickness and are of indefinite length.

Structure of the collagen fiber

Each collagen fiber is composed of parallel aggregations of many fibrils.

Each fibril is composed of bundles of parallel microfibrils.

The microfibrils can be seen only with the electron microscope and measure between 20-100 nm in thickness.

Each microfibril is composed chemically of molecules of tropocollagen, each of which is about 260 nm long and 1.5 nm thick.

Structure and development of the collagen

molecule

Each tropocollagen molecule is made up of three polypeptide chains, called units, that have a helical configuration and are coiled around the another in a right-handed fashion.

They are connected by crosslinks.

Each polypeptide chain is rich in glycine and contains the amino acids proline, hydroxyproline and hydroxylysine.

There is an overlapping of the parallel-running tropocollagen molecules along one-quarter of their length.

MOLECULAR STRUCTURE AND SUPRAMOLECULARMOLECULAR STRUCTURE AND SUPRAMOLECULARORGANIZATION OF THE COLLAGEN FIBERSORGANIZATION OF THE COLLAGEN FIBERS

COLLAGEN FIBRILS UNDER THE ELECTRON MICROSCOPE

Elastic fibers

Elastic fibers are composed of the protein elastin.

They are not as strong as collagen fibers.

They stretch easily but return to their original length when the stretching force is withdrawn.

Elastic fibers are formed by fibroblasts and smooth muscle cells.

Elastic fibers form the media and the elasticlaminae of the blood vessels.

Stains used to visualize: orcein & resorcin-fuchsin.

Reticular fibers

Reticular fibers are very thin collagen fibers and have similar periodic crossbinding.

Reticular fibers are often found to be continuous with collagen fibers.

Reticular fibers form delicate networks around blood vessels, adipose tissue cells and are present in lymphatic and hemopoietic tissues.

We stain them with silvernitrate (argyrophilic fibers)

Amorphous material

Communication between two type of interacting cells may occur by way of the ECM, which consists of material that is secreted by one or both of the cells into the space between the cells.

This matrix frequently contains a large concentration of complex polysaccharides, such as glycosaminoglycans.

These molecules are long chains of repeating disacharides.

They are often linked to proteins to form the proteoglycans.

Glycosaminoglycans (GAGs) in CT

Hyaluronic acid (synovial fluid, cartilage)

Dermatan sulfate: skin, tendon

Heparan sulfate: lung, liver, basal lamina

Keratan sulfate: cornea

Chondroitin 4-sulfate: bone, cornea, aorta

These molecules contain repeating disacharides (amino sugar + uronic acid). GAGs contain sulfate groups.

Proteoglycan moleculeattached to hyluronic acid

Collagen-proteoglycan complex

MOLECULAR STRUCTURE OF PROTEOGLYCANS (ATTACHMENT TO COLLAGEN)MOLECULAR STRUCTURE OF PROTEOGLYCANS (ATTACHMENT TO COLLAGEN)

Glycoproteins (laminin, fibronectin)

Fibronectin is a glycoprotein synthesized by fibroblasts and epithelial cells: it has binding sites for cells, collagen and glycosaminoglycans.

Laminin, a fibrous glycoprotein found in basal lamina, participates in the adhesion of epithelial cells.

Edema

Connective tissue ECM contains water (TISSUE FLUID), which comes from the capillaries with help of hydrostatic pressure (consequence of the pumping action of the heart).

The osmotic pressure of the blood proteins counterbalances the hydrostatic pressure.

The surplus tissue fluid in the CT will be drained by the lymph vessels.

Pathological conditions (e.g.: obstruction of lymph vessels) increase the amount of tissue fluid in the extracellular space this is EDEMA. It is visible as a swelling on the body surface.

Types of connective tissue

Loose connective tissue: connective tissue proper (e.g.: lamina propria)

Dense regular connective tissue (e.g.: tendon)

Dense irregular connective tissue (e.g.: periosteum, tunica albuginea)

Whartons jelly (e.g.: umbilical cord)

Adipose tissue: yellow and brown fat

Loose connective tissue(areolar tissue)

Blood vesselNerve

Dense regular connective tissue

TendonsLigamentsAponeurosesCornea (substantia propria)

Dense irregular CT:the capsule of organs(tunica albuginea);adventitia of vessels

Longitudinal section of a tendon

Adipose tissue with unilocular adipocytes

Adipose tissue with multilocular and unilocular adipocytes

Mucoid tissue: embryonic type of CTWhartons jelly in the umbilical cord

Mucous membrane:Mucous membrane:

-- EpitheliumEpithelium-- Basal laminaBasal lamina-- Lamina propriaLamina propria

The lamina propria is The lamina propria is a loose CT with manya loose CT with manycell types (granulocytes,cell types (granulocytes,lymphocytes, macrolymphocytes, macro--phages, mast cells,phages, mast cells,fibroblasts).fibroblasts).

Diseases of the CT

Scurvy: lack of vitamin C (this vitamin is needed for collagen synthesis). Atrophy of skin CT, ulceration of gums, hemorrhages.

Ehlers-Danlos disorder: collagen synthesis is faulty due to enzyme defect. Augmented skin elasticity and rupture of the eyeball (due to the weakness of sclera the fibrous coat of the eye).