Physiology - Epithelia

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General Features

  • Cancer prevalent due to high rates of division
  • Ectoderm epithelial origin
  • Covering (line all body surfaces) vs. glandular (functional unit) 
  • Bound tightly by specialised cell junctions
  • Supported by basement membrane (separates other tissues, intact means good prognosis)
  • Apical, lateral and basal (lamina densa, technically not a true membrane, structural attachment, filtration, compartmentalisation, signalling, scaffold, e.g lamins) all differ
  • Polarised (e.g. perpendicular to force applied i.e. wound)
  • Classification based on a. shape of top layer (squamous, cuboidal or columnar), b. no. cell layers (simple - all cells contact basal, stratified - only one layer in contact, or pseudostratified), c. surface specialisation (cilia, microvilli, keratinised), d. function - exchange (e.g. lungs), transport (e.g. kidney), movement (e.g. female reproductive tract), protective (e.g. urethra), or secretory (e.g. tear ducts)

Simple squamous covering - passive transport of gas/fluid, e.g. alveoli, endocardium

Stratified squamous non-keratinised covering - protection, surface squamous but basal cuboidal and divide constantly, e.g. cervix, oral cavity, oesophagus

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Surface Specialisations

Cilia e.g. respiratory tract and fallopian tubes

  • Extension of cytoskeleton composed of microtubule core (2 central, 9 outer)
  • Mobile - themselves and substances e.g. mucus, centrioles and other proteins
  • Primary - centrosomes migrate to plasma membrane to form cilia when not dividing

Microvilli

  • Very small (700nm) parallel bundles of actin
  • Increases SA for absorption but do not move 

Basolateral folds e.g. ion transport 

  • Deep invaginations increasing SA, many mitochondria

Inner/outer hair cells e.g. in ear

  • Completely different - stereocilia containing actin
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Glandular Epithelia

Exocrine

  • Via a duct
  • Merocrine - membrane-bound vesicles fuse with membrane e.g. sweat
  • Apocrine - release of product into vesicles e.g. mammary
  • Holocrine - entiire cell death e.g. sebaceous

Endocrine

  • Exocytosis of product which diffuses directly into bloodstream
  • Surrounded by capillaries 
  • e.g. lipids, thyroid hormones
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Connective Tissue Types

Loose

  • Substance exchange - collagen thin and sparse, ECM greater volume than fibres, viscous but permits diffusion (oxygen, nutrients, carbon dioxide)
  • Defense - adjacent to body surface and internal organs, intitial defense against pathogens when epithelium breached, wandering cells from local blood vessels, inflammatory response

Dense 

  • Irregular - mostly collagen fibres (bundles in various orientations), little ECM, strength e.g. intestinal submucosa
  • Regular - main constituent of ligaments (bone-bone), tendons (muscle-bone), and aponeuroses (fibrous tissue takes place of tendons in muscle sheets e.g. cornea, "six-pack" rectus abdominis, mainly collagen (parallel orientation), little ECM
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Tendons, Aponeuroses and Ligaments

Tendons

  • Parallel bundles of collagen
  • Rows of fibroblasts (tendinocytes) in between
  • Lack of elastic fibres (cannot stretch)
  • Epitendinium (outer capsule fibres less regular), endotendinium (connective tissue partitioning tendon, contianing blood vessels and nerves) 
  • Dense regular fasicles encased by dense irregular connective tissue

Aponeuroses

  • Collagen fibres arranged in layers
  • Adjacent (90 degrees) to each other = orthogonal array e.g cornea transparency 

Ligaments 

  • Fibres (mostly collagen) and fibroblasts in parallel but less regular than in tendons
  • If associated with nervous system - mostly consists of elastic fibres 
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Support Tissues

Collagen - most abundant fibre type

  • Flexible and high tensile strength
  • Varied diameter (15nm developing tissues, 300nm dense regular or tendons)
  • Straight but may form overlapping network
  • 20+ types e.g. type III collagen "reticular fibrils" - 20nm, branched, banding around blood vesselsetc., produces by fibroblasts, Schwann cells and smooth muscle cells, sign of tissue immaturity or initial scar formation (quick strength but replaces by stronger type I collagen) 

Elastin fibres

  • Prevents tearing and limits distensibility
  • Thinner and coiled
  • Interwoven with collagen - 3D mesh links
  • Central core of elastin surrounded by fibrillin
  • Produced by fibroblasts and smooth muscle
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Cell Junctions

  • Adherens (anchoring)- strong mechanical attachment, formed first as essential for further function, connected to actin cytoskeleton via intracellular adapter proteins e.g. catenins, extracellular domains from neighbouring cells bind together via cadherins (require Ca2+ to stabilise flexible linkers), NB: invasive carcinomas (epithelial origin) have often lost E-cadherin expression
  • Desmosomes (anchoring) - strong cell-cell adhesion, non-classical cadherins, adapter proteins e.g. desmoplakins, mutation = die during embryo development e.g. mice, if survive e.g. autoimmune pemphigus vulgaris
  • Tight - seal between cells (membranes pressed so prevent water/solute movement), regulate transport through epithelia, close but not strong (terms of tissue integrity), bubble-wrap appearance from rows of membrane proteins e.g. claudins, JAMs
  • Gap - adjacent cell passageways, molecules <2kDa (e.g. ions, metabolites, small signalling proteins), connexins (or innexins in insects), most mammalian tissues e.g. heart (contraction), neurons (rapid transmission of electrial signals)
  • Hemidesmosomes - cell-matrix adhesion, connect to basal lamina, shape, rigidity and cell signalling
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Extracellular Matrix

  • Lost in most histological procedures
  • Different proportions secreted by different tissues (hence different properties)
  • Mechanical and structural support, tensile strength, biochemical barrier, regulates cellular activity e.g. binds/retains growth factors, storage, embryonic tissue development interactions

Proteoglycans

  • 1. Heparan sulfate - to e.g. perlecan or agrin, regulates developmental processes, angiogenesis, blood coagulation, and tumour metastasis
  • 2. Chondroitin sulfate - tensile strength, neuroplasticity
  • 3. Keratan sulfate - cornea, cartilage, bones and horns
  • NB: 4. Hyaluronic acid - not found as a proteoglycan, resist compression by providing a counteracting turgor (swelling) force by absorbing significant amounts of water, load-bearing joints, interstitial gel, binds to CD44 (tumour metastasis, inflammation)

Proteins - laminins, fibronectin, collagen, elastin

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Connective Tissue Cells

  • Fibroblasts - secrete fibres (collagen and elastin) and ECM
  • Myofibroblasts - modified fibroblasts, contracticel machinery (wound closing), rough ER, gap junctions, similar to smooth muscle BUT single cells and no basal lamina
  • Chrondocytes - secrete cartilage ECM
  • Osteoblasts - secrete bone ECM
  • Adipocytes - store lipids
  • Macrophages
  • Mast cells - respond to previously-encountered antigens ("sensitisation"), release granules containing inflammatory and immune response promoting substances e.g. increase small blood vessel permeability
  • Lymphocytes
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Skin - Epidermis

  • Keratinocytes - a. Basal (site of production, mitosis, cuboidal/columnar, bound to BM by hemidesmosomes), b. Spinous (no mitosis, bound together by desmosomes, rich in keratohyalin granules and keratin (dark stain) bundles), c. Granular (flatten, lose nucleus, secrete lipids, change membrane comp.) d. Cornified (tight, flat, dead, cross-links with lipids = epidermal barrier "cornified envelope")
  • Melanocytes - produce melanin (skin colour, UV protection), in basal layer, numbers consistent but degree of activity changes, melanoprotein complexes pass through processes into keratinocytes (carried upwards), detect using Masson-Fontana stains (e.g. malignancy)
  • Langerhans Cells - immune systen (antigen presentation), mostly spinous, cytoplasmic processes between cells, pale HE stain, detect using metal impregnation or immunocytochemistry
  • Merkel Cells - sensory receptors of light touch, in basal layer, synaptic junctions with peripheral nerve endings (disk or tactile corpuscle), singly or grouped (fingertips), detect as in Langerhans
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Skin - Dermis

  • Epidermal appendages - hair, sweat glands
  • Supporting tissue
  • Sensory cells, nerves, fibroblasts
  • Two major cell layers - a. papillary (higher, collagen/elastin thin and vertical, more glycosaminoglycans and capillaries) b. reticular (lower, dense collagen and thick elastin, major blood and lymp vessels, oriented horizontally
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Skin - Hypodermis/Subcutis

  • Deepest layer
  • Adipose tissue and collagen fibres
  • Major blood supply and nerves
  • Insulator
  • Shock absorbance
  • Food store

Epidermal appendages

  • Hair and sebaceous glands = pilosebaceous unit, branched acinar gland, holocrine secretion, arrector pilli muscle aids in expulsion of sebum (lipids and waxes)
  • Apocrine sweat glands - discontinuous, genitali, armpits, anus, large coiled tubular gland with direct to surface duct, microbial activity (odour product breakdown, mark territory)
  • Eccrine/Merocrine swear glands - continuous, all over body esp. palms/forehead, temp. regulation, large coiled tubular gland with direct to surface duct, lipid rich (Na, K, Cl and urea so very hypotonic), a. clear calle (watery), b. dark cells (proteinaceous), 3. myoepithelial cells (contractile)
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