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Molecular Cell Biology

A. Cells in the Context of Tissue,

Organ and Organismal Architecture

B. Wound Healing

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Four Types of Vertebrate Tissue

1.Epithelium

2.Connective Tissue

3.Muscle

4.Nervous Tissue

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1. Architecture of Epithelium

Simple, Stratified, Pseudostratified, Transitional

Squamous, Cuboidal, Columnar

Ciliated or not

Examples:

Small Intestine = Simple Columnar Epithelium

Trachea = Ciliated Pseudostratified Columnar Epithelium

Blood Vessel = Simple Squamous Epithelium

Skin = Stratified Squamous Epithelium

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Structure equals Function

Small Intestine:

Simple Columnar Epithelium = absorption

Trachea:

Ciliated Pseudostratified Columnar Epithelium = filtering debris

Blood Vessel:

Simple Squamous Epithelium = gas exchange

Skin:

Stratified Squamous Epithelium = protective physical barrier

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Function:

1. absorption of nutrients

2. enzymatic digestion at neutral pH

3. multiple defensive mechanisms

Simple,

Columnar

Epithelium

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4 Cell types in Small Intestine

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Small Intestine

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Tracheal Epithelium

Ciliated PseudostratifiedColumnar Epithelium

with Goblet Cells

1. Mucus traps dust and air-borne microorganisms

2. Ciliar waving gets rid of

unwanted material

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The Vasculature: Simple, Squamous Epithelium

Gas Exchange Fluid Exchenge

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Epidermis of Skin

StratifiedSquamous

Epithelium

Creates tough,

waterproofbarrier

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Differentiation and Direction of Movement in Epidermis

Cornification

is the over-

production of

cytokeratins,ECM and the

adhesions to

a degree that

stops cellularmetabolism.

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2. Mesenchymal Cell Types and

Connective Tissues

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15/75Figure 23-52 Molecular Biology of the Cell( Garland Science 2008)

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The Fibroblast

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Loose Connective Tissue

Dense Regular CT

Dense Irregular CT

Elastic Connective Tissue

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Cartilage and the Chondrocyte

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Lacunar Structure of the Hyaline Cartilage

Extremely low blood flow

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Lacunar structure of the long bones

Osteoblasts

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Cortical Bone vs. Spongy Bone

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Marrow of

Long Bones

has Stem Cells

Cell Types of the Bone

St t t til d l b ilt b h d t

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Start out as cartilage models built by chondrocytes

Chondrocytes hypertrophy, calcify and die

Osteoblasts and osteoclasts finish up

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The Adipocyte

MesenchymalStem Cells are a

continuous source

of adipocytes

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Figure 23-47a Molecular Biology of the Cell( Garland Science 2008)

3. Contractile Tissue

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Arteries, veins

Lymphatic vessels

Gastrointestinal tract

Respiratory tractUrinary bladder

Reproductive tract

Urinary tract

Iris of the eye

Erector pili of skin

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4. Nervous Tissue

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Nerve Bundles

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Cutaneous Wound Healing

The skin is a complex organ...

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Many cells and activities involved

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Many cells and activities involved in Healing

Clotting

Scarring

Re-establishing

Function

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Four overlapping stages to wound healing

Hemostasis

Inflammation

Proliferation

Maturation

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Blood flows into the exposed ECM of

the injured tissue.

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RBC and Platelets Trapped in Fibrin Clot

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Clottingfactor

VII from the

blood contacts

tissue factoron

cells in the

damagedtissues to

activate clotting

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.

Camacho A , Dimsdale J E Psychosom Med 2000;62:326-3362000 by Lippincott Williams & Wilkins

Platelet activation in the clot makes them sticky

and releases their signal storage vesicles

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Positive feedback

activates even more

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Platelet activation

releases growthfactors by regulated

secretion

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Inflammation is a process mediated primarily

by WBC as part of our innate immunity

- Resident mast cells and macrophages

- Recruited monocytes and neutrophils

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Resident mast cells also degranulate

rubor= rednesscalor= heat

tumor= swelling

dolor= pain

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Activated mast cell activities

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Figure 1 Development and differentiation of macrophages.

Rickard A J , Young M J J Mol Endocrinol 2009;42:449-459

2011 Society for Endocrinology

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Activated macrophage activities

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Neutrophil Diapedesis

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Activated neutrophils are phagocytic

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Proliferation re-establishes tissue function

Reconnection of

the dermal

connective tissue

Integrity of the

epidermal layers

Re-establishment

of blood flow

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Reconnection of

the dermal CT

Cell Migration or Crawling

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Cell Migration or Crawling

The Basic Mechanism

Triggered by signals from outside the cell

Actin-myosin based movement

Requires attachments to outside to pull against

Gotta drag all of the cell contents along for the ride

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Chemotaxis

Circumferential receptors

Rho-family GTPases (monomeric)

Rho-dependent kinases

1. Actin monomer nucleotide exchange2. Actin fiber polymerization and disassembly

3. Myosin motor ATPase activity

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Figure 17-62 (part 1 of 3) Molecular Biology of the Cell( Garland Science 2008)

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Formation of the scar matrix

1. glycosaminoglycans

2. proteoglycans

3. fibrous proteins

4. elastic proteins

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Re-establishment of the

epidermal epithelium

involves both mitosis and

epithelial migration

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Also must reform the basal lamina

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Model depicting 31 integrin mediated functions of epidermis that contribute to wound

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Model depicting 31-integrin-mediated functions of epidermis that contribute to wound

healing.

Mitchell K et al. J Cell Sci 2009;122:1778-1787

2009 by The Company of Biologists Ltd

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Figure 23-34 Molecular Biology of the Cell( Garland Science 2008)

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Maturation Phase

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Wound contraction by myofibroblasts

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Stitches Perform Wound Contracture

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Collagen Remodeling

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Healing Abnormalities

Failure to heal: Excessive Inflammation

Excessive scarring: Wound Fibrosis Hypertrophic Scarring

Keloid Scarring

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Biofilms May Block Healing

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Hypertrophic scars result from failed

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Hypertrophic scars result from failed

fibroblast contracture

Dont extend beyond the original wound edge

Keloid scars result from excessive

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Keloid scars result from excessive

TGF-b receptors on fibroblasts

Extend to fibroblasts outside the wound

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