HistoReview_1stShift.pdf

UST FACULTY OF MEDICINE AND SURGERY Class of 2016

By: Sachi Estreller |Section B 1

Histology First Shifting Reviewer

CELL STRUCTURE AND FUNCTION Histology: study of normal structure

Cell: functional unit of all living organisms

Eukaryote: have defined nucleus enclosed by a membrane

Prokaryote: lacks membrane-bound organelles

Membrane Structure Plasmalemma: outer limiting membrane

Davson and Danieli: Classical Model o Trilaminar appearance of 2 protein

layers sandwiching a lipid layer

Singer and Nicholson: Fluid Mosaic Model o Phospholipid amphipathic bilayer, with

a hydrophilic head and a non-polar hydrophobic tail

o Polar head: glycerol conjugated to a nitrogenous compound

o Non-polar tail: two long-chain fatty acids (one unsaturated, one saturated)

o Fluidity and flexibility is due to presence of unsaturated fatty acids and cholesterol

Integral proteins o Incorporated within the membrane o Transmembrane if it spans the entire

thickness of the membrane

Peripheral proteins o Held to inner and outer surfaces by

weak electrostatic forces

Glycocalyx o Glycoproteins and glycolipids

projecting from the surface of the bilayer forming an outer coating involved in protection, cell recognition, formation of intercellular adhesions, and adsorption of molecules

o Role in histocompatibility

Functions o Filtration barrier o Ion permeability o Receptor sites o Cell recognition o Pinocytosis/ phagocytosis/ exocytosis

Cytoplasm Ground substance subdivided into:

o Endoplasm: manifest active streaming with cell components carried along

o Exoplasm: gel-like

Nucleus Largest organelle; found in all cells except RBC

Control center of the cell

Types: o Pyknotic Nucleus: small, condensed o Chromatic Nucleus: blotchy o Vesicular Nucleus: cleared out

appearance

Contents: o Chromatin

Contains DNA and proteins Heterochromatin: tightly

coiled inactive chromatin found in irregular clumps (in females, Barr Body exist as inactivated X chromosomes)

Euchromatin: electron-luscent, active in RNA synthesis

o Nucleoprotein Synthesis in the cytoplasm

and imported to the nucleus Histone proteins: LMW,

positively charged, bind tightly to DNA and control coiling and expression of genes

Non-Histone: enzymes for the synthesis of DNA and RNA

o RNA mRNA, tRNA, rRNA

Nucleolus and Protein Synthesis Nucleoli are sites of RNA synthesis and ribosome

assembly o Filamentous components: sites of

ribosomal RNA synthesis o Granular components: sites of

ribosome assembly

Intensely basophilic o Pars Amorpha/ Pars Fibrosa

Closely packed filaments on interior

o Nucleolonema/ Pars Granulosa Surrounds pars amorpha,

reticulum of anastomosing strands



Protein Synthesis o Transcription: DNA template copied to

form a complementary mRNA o Introns (non-coding sequences) are

spliced out of the mRNA before passing through the nuclear pore complex

o Translation: mRNA binds to ribosomes that read the sequence and make a chain of AAs for a particular protein

Ribosomes o Composed of a strand of RNA with

associated ribosomal proteins o Aligns mRNA so that tRNA will be

brought into position and AAs are added sequentially to form protein

o Polyribosomes: ribosomes attached to mRNA

o Ribosomes in RER Proteins are folded to form

tertiary structure, intrachain disulphide bonds are formed and first steps of glycosylation take place

Lysosomal proteins, proteins for export, and integral membrane proteins are made

o Free Ribosomes Proteins destined for the

cytoplasm, nucleus, and mitochondria are produced

Nuclear Envelope Thicker than cell membrane

Consist of 2 membranes enclosing a narrow perinuclear space that communicates with cisternae of RER

Inner and outer layers have phospholipid bilayer with different integral proteins

Outer lipid bilayer o Continuous with RER

Inner lipid bilayer o Contains the nuclear lamina, a layer of

intermediate filaments that consist of lamins that link inner membrane proteins and heterochromatin

Nuclear pore o Contains a nuclear pore complex,

cylindrical structure consisting of 50 proteins forming a central pore

o Permit the exchange of metabolites, macromolecules and ribosomal subunits

o Hold together the two lipid bilayers

Endoplasmic Reticulum Most abundant organelle

May have flattened and tubular cisterns Rough Endoplasmic Reticulum

With ribosomes

Active in protein synthesis Smooth Endoplasmic Reticulum

Without ribosomes

Active in lipid synthesis and membrane synthesis and repair

Synthesize cholesterol and phospholipids (FAs, and triglycerides are synthesized in cytoplasm)

Found in the liver o Rich in cytochrome P450 and plays a

role in the metabolism of glycogen and detoxification of metabolic by-products

Found in muscle o Called sarcoplasmic reticulum o Involved in storage and release of

calcium

Golgi Apparatus Stacked, saucer-shaped, membrane-bound

cisternae

Cis: convex, forming face

Trans: concave, maturing face

Process: o Proteins synthesized in RER

transported to cis Golgi face in coated vesicles (coat protein is called COP II)

o Coat proteins disengage and fuse with the cis face

o Proteins are passed from cistern to cistern by COP I coat proteins

o Glycosylation of proteins is completed by sequential addition of sugar residues and the proteins are packaged for transport to their final destination

o At the trans face, proteins are sorted into secretory vesicles destined for extracellular space, plasma membrane, or other organelles

o Secretory granules are liberated by exocytosis



Cell Transport Passive Diffusion

Dependent on presence of concentration gradient

Lipids and lipid-soluble molecules

In general, plasma membrane is impermeable to hydrophilic molecules; however, water, urea, and bicarbonate are able to pass through passive diffusion

Facilitated Diffusion

Concentration-dependent, requires presence of protein carriers

Example: Aquaporins o Allow water molecules to pass through

similar to passive diffusion Active Transport

Operates against concentration gradient

ATP is required Bulk Transport

Mediated by subcellular, transient structures known as coated vesicles

Transport proteins embedded in the membrane of a vesicle or soluble cargo within the lumen of the vesicle

Dependent on the fluidity and deformability of lipid membranes and mobility of intrinsic membrane proteins

Formation of a coat vesicle: o Coat proteins bind to membrane and

induce it to form a bud that is pinched off

o Formed vesicle sheds coat proteins and is moved by cytoskeleton to target site

Exocytosis o Secretory granules dock with plasma

membrane at the cell apex forming a transient opening called a porosome

o Secretory product exits through the porosome

o Secretory vesicle is recycled o Regulated secretion

Dependent on signal o Constitutive secretion

Continuous exocytosis

Receptor-mediated Endocytosis o Important in uptake of ligands that

bind to surface receptors o Receptors: intrinsic membrane

proteins with extracellular and cytoplasmic domains

o Process: Cytoplasmic tail of receptor

binds to clathrin coat protein in a coated pit

Receptors with ligands are concentrated in the coated pit

The pit buds off and forms coated vesicle

Vesicles lose clathrin coat and fuse with sorting endosomes

Sorting endosomes dissociate receptor and ligand (d/t acid PH)

Membrane and receptors are shuttled to recycling endosomes

Sorting endosome containing the ligand converts into a late endosome called a multivesicular body

Multivesicular body moved to golgi to fuse with lysosomes

Phagocytosis o Cells of the defense system ingest and

kill pathogenic organisms o Process:

Bacterium binds to cell receptors

Formation of pseudopodia that extend around bacterium

Enveloping pseudopodia form a phagosome

Phagosome fuses with lysosome phagolysosome

Bacterium is broken down by lysosome enzymes

Dead bacteria may be released and maintained in cytoplasm as residual body, or expelled from cell

Transmembrane Signalling

Signalling molecules bind and activate membrane receptors (usually enzymes)



Mitochondria and Energy Production Mitochondria

Elongated, cigar-shaped organelles

Very mobile, moves through microtubules

Localize at sites of maximum energy requirement

Contains DNA and ribosomes resembling chromosomes and ribosomes of bacteria

Undergo self-replication and synthesize some of their own constituent proteins

Aerobic respiration takes place in the matrix and inner membrane

Marker: succinate dehydrogenase

Four compartments: o Outer membrane

Contains porin which allows passage of small molecules

Contains enzymes that convert lipid substrates into forms that can be metabolized within mitochondrion

o Inner membrane Forms the cristae

o Mitochondrial Matrix Contains dense matrix

granules that are binding sites for calcium

Site of Kreb’s Cycle, protein and lipid synthesis

o Intramembranous Space Contains a variety of

enzymes

Energy Production and Storage

Cellular respiration: supplies energy stored in the form of ATP

Main substrates are simple sugars and lipids

Glycolysis o Begins in the cytosol where it is

degraded to form pyruvic acid o Pyruvic acid diffuses into mitochondria

where it is degraded to CO2 and H2O

Fatty Acid o Pass directly to mitochondria

Lysosomes Membrane-bound organelles containing

amorphous granular material

Lysosomal enzymes: proteases, lipases, nucleases, collectively known as acid hydrolases that are optimally active at PH 5

Involved in degradation of bacteria (heterophagy) and cellular organelles (autophagy)

Peroxisomes/ Microbodies Small, spherical, similar to lysosomes but contain

different material

Contain oxidases involved catabolic pathways which result in formation of hydrogen peroxide

Contain catalase that regulates hydrogen peroxide concentration

Nucleoid: central crystalloid structure that contains urate oxidase (not present in humans)

Annulate Lamellae Visible in Electron Microscopy

Parallel arrays of cisternae with small pores at regular intervals along length

Presence of diaphragms closing the pores

Functional significance not known

Cytoplasmic Inclusions Pigments

Lipofuscin o Represents an insoluble degradation

product of organelle turnover o “Wear and Tear” or “age” pigment o Residual bodies (remnants of

undigested molecules) may appear as brown lipofuscin granules

Melanin o Responsible for skin color

Lipids

Precursor molecules: FAs, triglycerides, and cholesterol

Lipid droplets in the cell do not have limiting membranes

Functions: o Maintain constant turn-over of cell

membranes o Store excess energy

Glycogen

Present in large amounts in liver cells

Glycogen granules are either: o Beta Particles: irregular single granules o Alpha Particles: glycogen rosettes

Others

Crystals

Secretory granules

Vacuoles



Cytoskeleton Functions:

o Maintains the shape and polarity of the cell

o Movement o Contractility o Reorganization of constituents in cell

division Microfilaments

Extremely fine strands of actin <8nm

Consist of two strings of bead-like subunits twisted together like a rope

Stabilized by calcium ions and associated with ATP molecules to provide energy for contraction

Functions: o Found in microvilli o Together with filamin, forms the cell

cortex which protects the cell against deformation

o Cell movement, pinocytosis, and phagocytosis

o Contractile properties Tonofilaments/ Intermediate Filaments

8-12 nm diameter

Purely structural function; not known to be contractile

Examples: o Cytokeratin: in epithelial supporting

network o Vimentin: in cells of mesodermal origin o Desmin: muscle cells o Glial fibrillary acidic protein: glial cells o Lamin: form layer in inner side of

nuclear membrane Microtubules

Appear as a circle composed of 13 globular subunits

Provide for alterations in cell shape and position of organelles; element of spindle apparatus

Originate from centriole found in centrosome

Microtubule associated proteins: stabilize tubular structure

o Capping Proteins Stabilize growing ends of the

tubules o Motor Proteins

Dynein Kinesin

Centrosome

Made up of a pair of centrioles (called diplosome) and centrosome matrix/ pericentriolar material

Self-duplicating

Centrioles: microtubule organizing center; nine triplets of microtubules

Aster: microtubules radiate outwards from the centrioles in a star-like arrangement

Delta Tubulin Ring Complexes: nucleus for polymerization of microtubules



CELL CYCLE AND REPLICATION Cell cycle: interval between mitotic divisions

S, G, M phases of the cell cycle are relatively constant in duration; G1 phase is highly variable

Terminologies Stem Cells

Labile cell

Relatively undifferentiated

Able to replace terminally differentiated cells Terminally Differentiated Cells

Lost ability to undergo mitosis

Permanent cells arrested at G0 phase Facultative Dividers

Do not normally divide but retain capacity to undergo mitosis when the need arises

Arrested at G2 phase Hypertrophy

Increase in bulk without multiplication of parts

Process in terminally differentiated cells

Examples: muscular hypertrophy, ventricular hypertrophy

Hyperplasia

Abnormal or unusual increase in cell number

Process in cells that retain capacity for mitosis

Common pre-neoplastic response to stimulus

Examples: endometrial hyperplasia, gingival hyperplasia, adrenal hyperplasia, benign prostatic hyperplasia

Atrophy

Decrease in size or wasting away of a tissue or body part

May happen in arrested development or progressive decline of cellular processes

Examples: atrophy of the thymus, muscleatrophy Metaplasia

Transformation of one tissue to another or one differentiated type of cell to another differentiated type

Occurs for the body to be able to adapt better to changing conditions

Usually reversible; when stimulus or environmental condition that induced metaplasia is removed

Example: barrett’s esophagus

Interphase G1 Phase

Between end of M phase and beginning of S phase

Cells differentiate and perform specialized functions

Usually the longest S Phase

Synthesis phase when nuclear DNA is replicated

Completed before onset of mitosis G2 Phase

Between end of S phase and beginning of M phase

Cells prepare for mitotic division

Prolonged phase in facultative dividers G0 Phase

State of continuous differentiated function

State of terminally differentiated cells; may last for entire lifespan

Mitosis Results in formation of two daughter cell

(diploid, genetically identical)

No duplication Chromosomes

In humans, there are 46 chromosomes, paired in 22 homologous pairs called autosomes and 2 sex chromosomes

Chromatids: identical chromosomes resulting from S phase

Karyotyping: examination of chromosomes of dividing cells

DNA o Consist of a backbone containing

alternating deoxyribose and phosphate moieties

o Deoxyribose: bound to a purine or pyrimidine base; linked to a complementary base on the other strand

o Bases: adenine, cytosine, thymine, guanine

o Genetic code: dependent on sequence of bases

Bases are read in groups of three called codons; each codon codes for an AA



Mitotic Apparatus

Comprises a spindle of longitudinally arranged microtubules extending between a pair of centrioles at each pole of the dividing cell

Visible only during the M phase; disaggregates after mitosis is completed

Phases of Mitosis

Prophase o Start: chromosomes first become

visible in nucleus o Chromosomes become increasingly

condensed and shortened o Nucleoli disappear o Pairs of centriole migrate towards

opposite poles of the cell while the spindle of microtubules is formed

o End: dissolution of nuclear envelope

Metaphase o Mitotic spindle moves to nuclear area

and duplicated chromosomes attached at the kinetochore to another group of microtubules in the spindle

o Kinetochore DNA and protein structure

on the chromosome located at the centromere that binds the duplicated chromosomes (chromatids) together

Metaphase checkpoint: kinetochore controls entry of cell into the anaphase; mitosis does not proceed unless all chromatids are aligned at the cell equator

o Chromosomes are arranged in the metaphase plate

Anaphase o Start: splitting of centromere o Mitotic spindle lengthens o Centrioles pulled apart and chromatids

are drawn to opposite ends of the spindle

Telophase o Chromosomes uncoil and regain

interphase conformation o Nuclear envelope reforms and nucleoli

become visible o Cytokinesis: plane of division defined

by position of spindle equator, formation of cleavage furrow

Meiosis Produces gametes that contains haploid number

of chromosomes

Involves one reduplication of chromosomes followed by two cell divisions

Process o Duplication of chromosomes o Chiasma formation: crossing over of

chromatids that provides genetic variability

o First meiotic division: separation of pairs of chromatids still joined at centromere

o Second meiotic division: splitting of chromatids by pulling apart centromeres

In males: four gametes are produced and mature into spermatozoon

In females: one large gamete matures into ovum, while the other three gametes degenerate and form polar bodies

Apoptosis Highly controlled and ordered mechanism by

which cells are removed in a way that causes minimal disruption in surrounding tissue

Active process that requires energy; may be normal or pathologic

Different from necrosis, which is associated with pathology and is characterized by the inability of cells to produce ATP and maintain homeostasis

Process: o Extracellular signal molecule binds to

Fas, the death receptor; OR o Intracellular signals such as DNA

damage cytochrome C release from mitochondria into cytoplasm triggers the event

o Caspase cascade is activated: enzymes cleave cellular proteins

Pyknosis: condensation of nuclear chromatin

Cell shrinks away from neighboring cells

Karryorhexis: nuclear material is fragmented, dissolution of nuclear membrane

Karyolysis: entire cell breaks up

Apoptotic Body: fragments that contain nuclear material; phagocytosed by macrophages or neighbouring cells



EPITHELIAL TISSUE Derived from ectoderm, mesoderm, and

endoderm

Endothelium in vessels and mesothelium in cavity linings are derived from mesoderm and were not originally classified as epithelium

Functions o Cover or line body surfaces o Selective diffusion o Absorption or secretion o Physical protection and containment

Majority contain the intermediate filament, cytokeratin

Critically dependent on diffusion of oxygen and metabolites from supporting tissue because basement membrane is not penetrated by blood vessels

Classification of Epithelia Traditionally classified according to

morphological characteristics: o Number of cell layers o Shape of component cells o Surface specializations

Simple Epithelia

Single layer of cells

Functions in selective diffusion, absorption, and secretion

Simple Squamous Epithelium o Flattened, irregularly shaped o Sometimes termed as pavemented

epithelium o Found in lining surfaces involved in

diffusion of gases or fluids (eg. vessels and cavity linings)

Simple Cuboidal Epithelium o Square, but polygonal in surface view o Nucleus usually round and centrally

located o Found in small ducts or tubules (eg.

renal tubules)

Simple Columnar Epithelium o Taller and columnar cells o Nuclei are elongated and may be

located towards base, center, or apex (polarity)

o Found in lining of absorptive surfaces in the small intestine or secretory surfaces in the stomach (eg. gallbladder)

Simple Columnar Ciliated Epithelium o Found mainly in female reproductive

tract o Have surface specializations called cilia

(discussed later)

Pseudostratified Columnar Epithelium o Single layer of cells that conveys the

erroneous impression that there is more than 1 layer

o All cells rest on basement membrane but nuclei are disposed at different polarities

o Found in the airways of the respiratory system

o Different from TRUE stratified epithelia in two aspects:

Pseudostratified cells exhibit polarity of nuclei, mainly confined in basal 2/3 of epithelium

Cilia never present in true stratified epithelia

Stratified Epithelia

has two or more layers of cells

Functions mainly for protection

Stratified Squamous Epithelium o Found in uterine cervix and epidermis

of the skin Basal layer: cuboidal Intermediate layer:

polygonal Surface layer: flattened

o Withstand abrasion but not desiccation

Stratified Cuboidal Epithelium o Thin, stratified layers (2-3) of cuboidal

cells o Found in lining of the larger excretory

ducts of the exocrine glands

Transitional Epithelium o Found only in urinary tract

Basal layer: cuboidal Intermediate layer:

polygonal Surface layer: umbrella cells

that may contain 2 nuclei In the stretched state,

intermediate and surface layers are flattened

o Accommodate stretch and withstand toxicity of urine

Neuroepithelium o Chief cell surrounded by supporting

cells made up of columnar and basal cells



Glandular Epithelia

Invaginations of epithelial cell surfaces

Exocrine o Connected to a surface epithelium by a

branching system of ducts

Endocrine o Lost connection to epithelial surface

and release secretions directly into blood

Membrane Specializations Intercellular surface specializations function to

form a continuous cohesive layer of epithelia and also for cell communication

Luminal surface specializations function for secretion, absorption, and mobilization

Basal surface specializations provide anchorage and structural support

Intercellular Junctions

Junctional Complex o Composed of tight junction, zonula

adherens, and desmosomes

Zonula Occludens o Also called tight junctions o Forms a continuous circumferential

band that: Block passage of molecules Separate apical and

basolateral plasma membrane compartments

o Sealing strands stitch membranes together, with each strand comprising of two molecules of claudin on the plasma membrane and actin on the cytoplasm

o Fascia Ocludens: structurally similar but discontinuous strips of tight junctions that are found in blood vessels

Zonula Adherens o Form a contractile circumferential

band o Transmembrane protein: cadherin o Anchoring proteins: catenin, vinculin,

alpha actinin) o Bind to actin molecules

Macula Adherens o Also called desmosomes o Transmembrane protein: cadherin o Anchoring protein: desmoplakin,

plakoglobin) o Bind to intermediate filaments

Gap Junctions o Conduit for passage of small molecules

between adjacent cells; large molecules and negative ions are denied passage

o Important in the control of growth, development, cell recognition, and differentiation

o Contains transmembrane channels called connexons, made up of 6 connexin proteins

Hemidesmosomes

Variant of desmosomes that bind intermediate filaments linking the basement of the cell to the basement membrane

Transmembrane protein: integrins

Anchoring protein: plectin

Bind to intermediate filament

Extracellular binding site: laminins in BM Cilia

Beat in wave-like synchronous pattern

Function in propelling mucus or fluid in a consistent direction over the epithelial surface

Axoneme: central core consisting of 20 microtubules arranged as a central pair surrounded by 9 peripheral doublets

Basal Body: nine microtubule triplets continuous with the base of the cilium

Dynein: ATPase that fuels ciliary movement Microvilli

Minute finger-like projections on luminal plasma membrane

Termed as brush borders in light microscopy

Core contains actin microfilaments which insert into the terminal web anchored to the zonula adherens

Stereocilia

Extremely long microvilli found in the male reproductive tract

Facilitate absorptive processes Goblet Cell

Modified columnar epithelial cells that synthesize and secrete mucus

Contains aggregation of mucigen granules which are released through exocytosis and combines with water to form mucus

Mucigen: mix of acidic and neutral proteoglycans

RER and Golgi apparatus are prominent



Keratin

Occurs in Stratified Squamous Epithelium

During maturation, cells accumulate cross-linked cytokeratin resulting in the formation of a tough, non-living surface layer of squames consisting of a protein called keratin

In the keratin layer nuclei become pyknotic then disappear

Exocrine Glands Classification by Means of Secretion

Merocrine (Eccrine) o Most common form of secretion

through exocytosis

Apocrine o Discharge of free, unbroken,

membrane-bound vesicles o In lipid secreting glands in the breasts

and some sweat glands

Holocrine o Discharge of whole secretory cells with

subsequent disintegration of cells to release the product

o In sebaceous glands Morphological Classification

Simple Tubular o Single, straight, tubular o In large intestine

Simple Coiled Tubular o Single, coiled in 3D o In sweat glands

Simple Branched Tubular o Several tubulosecretory portions that

converge in a single unbranched duct o In the stomach

Compound Branched Tubular o In the duodenum

Simple Acinar o Rounded exocrine secretory unit o In penile urethra

Simple Branched Acinar o Several secretory acini empyting into a

single excretory duct o In sebaceous glands

Compound Acinar o Acinar secretory units draining into a

branched duct system o In pancreas

Compound Tubuloacinar o Branched tubular, branched acinar,

and branched tubular with acinar end pieces called demilunes

o In submandibular gland

2 types of secretory cells

Mucous o Tubular o Acidophilic o Striated granular o With canaliculi o Bounded nucleus and narrow lumen

Serous: o Acinar and demilunes o Basophilic o Reticulated o No canaliculi o Flattened nucleus, wide lumen

Endocrine Glands Consist of clusters or cords of secretory cells

surrounded by a rich network of blood vessels

Most release more than one hormone

Some consist of more than one type of secretory cell

Hormone secretion is controlled by metabolic factors, the nervous system, and other hormones

Follicular Endocrine Gland

Seen in thyroid gland

Stores hormone in spherical cavities enclosed by secretory cells



CONNECTIVE TISSUE Mesodermal in origin

o Mesencymal cells are stellate or spindle-shaped with cytoplasmic extensions; differentiate into all cell types found in mature supporting tissue

Functions o Structural and metabolic support o Exchange of nutrients and metabolites o Protection and tissue repair o Insulation o Hematopoietic and immunologic

Connective Tissue Cells Fibroblast

Secrete ECM in most tissues

Dominant RER and Golgi Apparatus reflecting dominant protein-secreting function

Maintain integrity of supporting tissues by continuous slow turnover of ECM constituents

Chondrocytes and Osteocytes

Secrete ECM in cartilage and bone

Myofibrolasts

Have additional contractile properties

Adipocytes

Storage of metabolism and fat Defense Cells of Supporting Tissue

May be fixed (macrophages and mast cells) or wandering (leukocytes)

Reticuloendothelial system o Refers to phagocytic cell network

located in the marrow, spleen, lymph node, and liver that have a supporting framework of reticular fibers

Mast Cells o Found in skin, GI lining, blood vessels,

and lining of peritoneal cavity. o Similar to basophils with some

differentiating properties: Less condensed chromatin More uniform distribution of

processes > cytoplasmic filaments and

granules Lack of glycogen granules

o Mast cell degranulation results in the release of histamine and other vasoactive mediators which induce immediate hypersensitivity and anaphylactic shock

Macrophages o Active cells exhibit irregular

cytoplasmic projections or pseudopodia which are involved in amoeboid movement and phagocytosis

o Functions: Tissue scavengers Antigen presenting cells

during opsonisation Cytokine secretion that

enhances immune response Lymphokines: increase the

metabolic and phagocytic activity of macrophages

Connective Tissue Fibers Collagen Fibers

Most abundant protein in the body

Most notable function is tensile strength

Secreted in the form of tropocollagen that polymerize in the ECM to form collagen

Types: o Type I: in fibrous supporting tissue,

dermis of the skin, tendons, ligaments, and bone

o Type II: hyaline cartilage o Type III: reticulin, found in highly

cellular tisues also called argyrophillic

fibers because it is stained through silver impregnation

o Type IV: basement membrane o Type VII: anchoring fibrils for basement

membrane Elastin Fibers

Has stretch and elasticity

Secreted in the form of tropoelastin

Deposition of elastin as fibers requires that presence of fibrillin (structural glycoprotein)

Found in lungs, skin, urinary bladder, and blood vessels

Ground Substance Consist of GAGs or mucopolysacharrides

GAG: double sugar units usually uronic acid and amino acid sugar (N-acetylglucosamin and N-acetylgalactosamine)

Hyaluronic Acid: predominant GAG, without sulphate side groups

Other GAGs: chondroitin-4 and 6- sulphate, dermatan sulphate, heparin and heparin sulphate, and keratin sulphate

GAGs are hydrophilic ECF confers turgor



Structural Glycoproteins Fibrillary: fibrillin, fibronectin

Non-Fibrillary: laminin, entactin, tenascin

Function as links between cells and ECM Fibrillin

Enhance adhesion between other extracellular constituents and deposition of fibers in elastin

Fibronectin

Control deposition and orientation of collagen in ECM

Enhance binding of cell to extracellular material Laminin

Form links between cell membranes and basement membrane

Entactin

Bind laminin to Type IV collagen in basement membrane

Tenascin

Binds to integrins and play a role in embryonic nerve cell growth

Basement Membrane Sheet-like arrangements of ECM that act as

interface between support tissues and parenchymal cells

Main constituents: heparin sulphate, collagen type IV, fibronectin, laminin, and entactin

Functions: o Metabolic support o Control of epithelial growth and

differentiation o Regulation of permeability

Layers: o Lamina Lucida

Electron lucent Mainly type IV collagen

bound to basal plasma membrane by laminin

Entactin mediates binding of laminin to collagen

o Lamina Densa Electron dense, intermediate

layer o Lamina Fibroreticularis

Merges with underlying supporting tissue

Mainly type III collagen bound to integrin of parenchymal basal membrane by fibronectin

Adult Connective Tissue Loose Areolar Connective Tissue

Few collagen fibers present

Found in lamina propria, superficial and deep fascia

Dense Regular Connective Tissue

Compact collagen fibers oriented unidirectionally

Found in tendons, ligaments, and aponeurosis

Dense Irregular Connective Tissue

Compact collagen fibers oriented multidirectionally

Found in GIT, dermis, periosteum, perichondrium

Elastic Connective Tissue

Contain elastin fibers, slender and refractile

Found in wall of hollow organs, blood vessels, trachea, bronchi, yellow ligaments, suspensory ligaments

Reticular Connective Tissue

Contains reticulin fibers

Supporting framework of hematopoietic and lymphoid organs

Adipose Connective Tissue

Adipocytes o Adapted for storage of fat in lipid

droplets o Derived from mesenchymal cells that

develop as lipoblasts o Signet-ring appearance with the

nucleus at the periphery o Secrete adipocytokines that modulate

energy metabolism o Generally has a rich blood supply o Have receptors for insulin,

glucocorticoids, growth hormone and noradrenaline

Stored fat from: o Triglycerides from liver o Circulating dietary fat o Triglycerides from glucose within

adipocytes

Types: o White Adipose Tissue

Unilocular Energy store, thermal

insulator, and cushion o Brown Adipose Tissue

Multilocular Found in newborns and

hibernating mammals



Function in body temperature regulation: non-shivering thermogenesis induced by cold stress

Contains thermogenin which uncouples mitochondrial metabolism from production of ATP to produce heat

Cytochrome accounts for the brown color of adipocytes

Embryonic Connective Tissue Mesencymal Connective Tissue

With capacity for differentiation

Mucuous Connective Tissue

Formed by primitive fibroblasts (spindle-shaped/stellate)

Wharton’s jelly of umbilical cord

Specialized Connective Tissue Cartilage, bone, and blood to be discussed in a

later section



SKELETAL TISSUES Mesodermal in origin

Rigid form of connective tissue due to calcification of ground substance

Inorganic elements: Mg, Ca, Na

Organic elements: calcified matrix

Functions: o Internal support o Attachment of muscles and tendons o Contains bone marrow o Protect vital organs o Calcium storage

Cartilage provides smooth articular surface and structural

support; also important in bone formation

made up to extracellular matrix: ground substance + fibers

Ground Substance o Made up of proteoglycans o Accound for solid and flexible

properties of cartilage o Sulphated GAGs predominate such as

chondrotin and keratin sulfate

Most are avascular thus exchange of metabolites between chondrocytes and surrounding tissue depends on diffusion through water solvation of ground substance

Cartilage Formation

Primitive mesenchymal cells differentiate to chondroblasts which synthesize ground substance and fiber

Chondroblasts o Separated by cartilaginous matrix and

undergo mitotic division in separate areas, maturing into chondrocytes

Chondrocytes o Maintain the integrity of the cartilage

matrix o Arranged in clusters of 2-4 enclosed by

amorphous cartilage matrix o Involved in synthesis of ground

substance and fibers of the ECM o Have prominent RER and Golgi

Apparatus

Appositional Growth o Through the perichondrium, a layer

surrounding mature cartilage composed of fibers and spindle-shaped cells

o Cells transform into chondroblasts and produce new cartilage

Interstitiial Growth o Occurs through further division of

chondrocytes trapped within mature cartilage

o Mature cartilage has little capacity to repair and regenerate due to poor vascular supply

Hyaline Cartilage

Most common type

Found in nasal septum, larynx, tracheal rings, articular surfaces

Precursor in the developing bone

Consists of collagen type II (except articular cartilage)

Elastic Cartilage

Found in external ear, epiglottis, laryngeal cartilage, and walls of Eustachian tube

Elasticity is derived from elastic fibers in the cartilage matrix

Fibrocartilage

Found in intervertebral discs, articular cartilage, and pubic symphysis, joint capsules, ligaments, and tendons

Chondrocytes typically arranged in rows between dense collagen layers

Bone Provides a rigid protective and supporting

framework

Also serves as a calcium reservoir

Composed of cells and type I collagen called osteoid, mineralized by deposition of calcium hydroxypatite

Cells of the Bone

Osteoprogenitor o Primitive mesenchymal cell line where

osteoblasts and osteoclasts originate

Osteoblasts o Synthesize osteoid and mediate its

mineralization; lined up in bone surfaces

o Inactive: spindle shaped; active: cuboidal

Osteocytes o Inactive osteoblasts embedded in

formed bone; assist in nutrition

Osteoclast o Phagocytic, multi-nucleated cells that

erode bone for turnover and refashioning; come from monocyte-macrophage cell line



o Found in Howship’s lacunae, depressions of resorbed bone

o With a ruffled border formed by microvilli that secrete organic acids and proteolytic enzymes

Types of Bone According to Collagen Organization

Woven Bone o Collagen fibers arranged randomly and

irregularly o Fabricated during periods of rapid

bone growth: embryogenesis, reactive, neoplastic

o Hypercellular with large osteocytes and lacunae distributed in haphazard fashion

o Prone to greenstick fracture o Pleomorphic osteocytes

Lamellar Bone o Collagen fibers arranged in parallel o Synthesized more slowly; stronger o Less cellular, small osteocytes and

lacunae o Uniform osteocyte morphology o May be compact or spongy

Compact Bone (Substantia Compacta)

Parallel columns made up of concentric bone layers surrounding the haversian canal

Haversian System o Haversian channel

Contains lymphatics, blood vessels, nerves

o Volkmann’s Canal Connect neurovascular

bundles in haversian canals with andosteum and periosteum

o Lacunae Containing ostecytes and are

seen in between lamella o Canaliculi

Minute interconnecting canals in between lacunae containing cytoplasmic extensions of osteocytes

Provide passage for circulation of ECF and diffusion of metabolites between lacunae and vessels of haversian canals

o Concentric Lamella Internal/Endosteal Lamella External/Periosteal Lamella Interstitial Lamella: remnants

of resorbed lamellae no longer surrounding haversian canals

o Periosteum Bound to underlying bone by

Sharpey’s Fibers Layer of condensed fibrous

tissue containing osteogenic cells

Spongy Bone (Substantia Spongiosa)

Irregular branching bony spicules forming a network of interconnecting spaces

With thin trabeculae made up of irregular lamellae

Trabeculae is lined by thin endosteum containing flat inactive osteoblasts

Number, thickness, and orientation are dependent on the stresses to which the bone is exposed

Contains red (hematopoietic) and yellow (adipose) marrow

No haversian system Types of Bone According to Structure

Long Bone o Diaphysis

Mostly compact bone o Epiphysis

Mostly spongy bone o Epiphyseal Plate

In between epiphysis and diaphysis

o Metaphysis Transition connecting

epiphyseal plate and diaphysis

o Periosteum and Endosteum Lining of outside and inside

of bone

Flat Bone o Made up of 2 layers of compact bone

(inner and outer tables) surrounding spongy bone layer (diploe)



Joints Synovial Joint

Allows extensive movement

Also known as diarthroses

Articular cartilage o Hyaline cartilage that covers articular

surfaces o Infers resistance to compressive forces

Synovium o Secretory cell layer that secretes

synovial fluid in the cavity to facilitate smooth articulation

o May be fibrous (dense), areolar (loose), or adipose (fat) synovium

o Synovial fluid contains: Hyaluronic acid and

associated glycoproteins from Type B Synoviocytes

Transudate from capillaries Leucocytes and monocytes

o Type A Synoviocytes With extensive golgi complex

and lysosomes o Type B Synoviocytes

With extensive endoplasmic reticulum

Cruciate ligaments o Internal ligaments that limit joint

movement together with fibrous joint capsule and external fibro-elastic ligaments

Non-Synovial Joints

Have limited movement

No free articular surface, instead joined by dense collagenous tissue

Types: o Dense fibrous Tissue

Called syndesmoses that transform to synostoses when replaced by bone

Found in sutures of the skull o Hyaline Cartilage

Called synchondrosis Found in union of first rib

with sternum o Fibrocartilage

Called symphyses Found in pubic symphysis

and intervertebral discs

Tendon Tough flexible straps that connect muscles to

bone

Composed of compact linear collagen fibers with nuclei of inactive fibroblasts

Poorly vascularised and heals slowly

Anchor to muscle through myotendinous junctions

Anchor to bone through the periosteum or Sharpey’s Fibers

Bone Development and Growth Bone Matrix and Mineralization

70% inorganic salts o Mainly calcium and phosphate in the

form of hydroxypatite crystals o Magnesium carbonate o Sodium o Potassium

30% organic o Type I collagen creates hole zones, the

initial site for mineralization o Ground substance proteoglycans

consist of hyaluronic acid and chondroitin sulphate

o Osteocalcin: involved in binding calcium during mineralization

o Osteonectin: bridging function between collagen and mineral component

o Sialoprotein

Process o Collagen and other organic

components synthesized from RER of osteoblasts Golgi Apparatus secreted as osteoids

o After maturation phase, calcium phosphate salts precipitate in the hole zones

o Pyrophosphate: inhibitor that controls bone mineralization

o Alkaline Phosphatase: neutralize effect of pyrophosphate

Intramembranous Ossification

Skull vault, maxilla, mandible

Occurs within membranes of condensed, primitive mesenchymal tissue

Process: o Mesenchymal cells differentiate into

osteoblasts that begin synthesis of osteoid at “centers of ossification”

o Mineralization of osteoid o Osteoblasts trapped in lacunae evolve

into osteocytes and cytoplasmic extensions shrink and form canaliculi



o Osteoprogenitor cells continue to form osteoblasts

o Fusion of adjacent ossification centers occurs

o Woven bone is remodelled by osteoclastic activity and subsequent osteoblastic deposition of mature compact bone

Endochondral Ossification

Long bones, vertebrae, pelvis, skull base

Permits functional stress to be sustained during skeletal growth

Process of Primary Ossification o Zone of Reserve Cartilage

Cartilage model is first formed in hyaline cartilage

o Zone of Proliferation Appositional growth occurs

to form the different parts of bone

o Zone of Maturation Chondrocytes within the

model enlarge and resorb the cartilage so as to leave perforated trabeculae of cartilage matrix

o Zone of Hypertrophy and Calcification Cartilage matrix is ossified

o Zone of Cartilage Degeneration Chondrocytes degenerate,

primitive mesenchymal cells and blood vessels invade the spaces occupied by chondrocytes and differentiate into osteoblasts and hematopoietic cells

o Osteogenic Zone Osteoblasts begin to form

woven bone o Perichondrium develops osteogenic

potential and assumes the role of periosteum

o Periosteum lays down a thin layer of bone on the surface

o Results in bony diaphysial shaft with cartilaginous epiphyses at each end

Process of Secondary Ossification o Conversion of central epiphyseal

cartilage into bone

Documents

HistoReview_1stShift.pdf