Chapter 3Chapter 3

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Dee Unglaub Silverthorn, Ph.D.

H ^UMAN P ^HYSIOLOGY H ^UMAN P ^HYSIOLOGY

AN INTEGRATED APPROACH

T H I R D E D I T I O N

Chapter 3 Chapter 3

Cells and Tissues

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About this Chapter About this Chapter

• Cell structure and types

• Cell differentiation

• Compartmentalization

• Mechanical properties and cell functions

• Cell junctions

• Tissue types and characteristics

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Overview: Cells to Organ Systems

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• Cytosol

• Organelles

• Inclusion

• Dissolved

• Insoluble Cell Cytoplasm Cell Cytoplasm

Figure 3-3: A map for the study of cell structure

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• Ribosomes

• Free

• Fixed

• Protein synthesis

Nonmenbranous Organelles

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Nonmenbranous Organelles Nonmenbranous Organelles

Figure 3-6: Ribosomes are nonmembranous organelles composed of RNA and protein

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• Internal lumen and membranes for protected reactions

• Mitochondria: Generates cell energy (ATP) , have DNA

Membranous Organelles: Create cell compartments

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• Smooth ER: Lipid synthesis & conversion

• Rough ER: Ribosomes, protein assembly &

transport vesicles

Endoplasmic Reticulum (ER) ad Ribosomes

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• Protein packaging

• Secretory vesicles

• Secreted to E C F Golgi Apparatus

Golgi Apparatus

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Golgi Apparatus Golgi Apparatus

Figure 3-11: The Golgi apparatus

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• Lysosomes

• Enzymes

• Intracellular digestion

• Peroxisomes

• Hydrogen peroxide

• Detoxification

• Fatty acid degradation Cytoplasmic Vesicles Cytoplasmic Vesicles

Figure 3-12: Lysosomes and peroxisomes

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• Nuclear envelope

• Nuclear pore complex

• Chromatin

• DNA form genes

• Nucleoli

• DNA concentrations

• Control rRNA synthesis Nucleus

Nucleus

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Nucleus Nucleus

Figure 3-13: The nucleus

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Nuclear Envelope- Double Phospholipid Bilayer

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Overview: Cells to Organ Systems Overview: Cells to Organ Systems

Figure 3-4a-c: Anatomy Summary: Levels of Organization—System to Cell

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Cell Membrane

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The importance of selectively permeable membranes

•Membranes are physical barriers of cells and subcellular compartments controlling material exchange

between the internal environment and the extracellular environment

•A membrane is essentially a

hydrophobic permeability barrier consisting of phospholipids,

glycolipids, and membrane proteins

•Membranes contain amphipathic molecules such as phosphatidyl ethanolamine, an example of

phosphoglycerides, the major class of membrane phospholipids in most cells.

Polar

headNonpolar tail

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Cell Junctions:

• Gap Junctions: Simplest Cell-Cell Junction.

Can open and close. Present in many tissues. Proteins associated with:

Connexins

• Tight Junctions: Cell-Cell Junction in

Epithelial tissue that does not allow much movement of material between cells.

Proteins associated with: Claudins and Occludins. Blood Brain Barrier

• Anchoring Junctions: Attach cells to each

other (cell-cell anchoring junction) or to the

ECM (cell-matrix anchoring junction).

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Junctions Junctions

Figure 3-14: Types of cell junctions

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Key Junction Proteins:

Connexin, cadherins, occludin & integrins Key Junction Proteins:

Connexin, cadherins, occludin & integrins

Figure 3-15: A map of cell junctions

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Intracellular Proteins Intracellular Proteins

• Tubulin (microtubules)

• Actin- (microfilaments)

• Myosin (intermediate filaments)

• Keratin (intermediate filaments)

• Neurofilament protein

• Kinesin

• Dynein

(26)

Cell Membrane Proteins Cell Membrane Proteins

• Connexin

• Claudin

• Occludin

• Cadherin

• Integrin

• Selectin

(27)

Extracellular Matrix Proteins Extracellular Matrix Proteins

• Collagen

• Elastin

• Fibrillin

• Fibronectin

• Laminin

(28)

• Cell to cell

• Gap junctions: between heart muscle cells

• Tight junctions: blood brain barrier

• Anchoring junctions:

• Desmosomes- attach to intermediate filaments of cytoskeleton

• Adherens Junctions- link actin in adjacent cells

Junctions

(29)

Junctions Junctions

• Cell to matrix: Anchoring Junctions

• Focal Adhesions- junction between

intracellular actin and matrix proteins

• Hemidesmosomes- strong junction that

ties a cell to the matrix proteins

(30)

Types of Anchoring Junctions Types of Anchoring Junctions

• Cell- Cell Anchoring Junctions:

Adherens Junction- links actin in adjacent cells and Desmosomes- attach to intermediate

filaments of cytoskeleton

• Cell-Matrix Anchoring Junctions:

--Focal adhesions- bind intracellular actin to different matrix

proteins such as fibronectin --Hemidesmosomes- strong junctions

that anchor intermediate fibers of the cytoskeleton to matrix proteins such as

laminin

(31)

Cytoskeleton Cytoskeleton

• Three Dimensional Scaffold of Actin,

Intermediate Filaments and Microtubules

• Responsible for Cell Shape, internal organization, movement, intracellular

transport and assembly of cells into tissue

(32)

Cytoskeleton Cytoskeleton

Figure 3-7: The cytoskeleton and cytoplasmic protein fibers

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• Strength

• Support

• Shape

• Transport

• Cell to cell links Cytoskeleton

Cytoskeleton

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Cytoskeleton Cytoskeleton

• Microfilaments: Composed of Actin

• Intermediate Filaments: Composed of

Myosin, Keratin, Neurofilament and other proteins

• Microtubules: Largest cytoplasmic protein fibers. Creates centrioles, cilia and flagella.

Composed of tubulin (a globular protein)

• Motor Proteins: Composed of multiple protein chains that bind to the

cytoskeleton. Proteins involved include

myosin, Kinesins and Dyneins

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The Centrosome The Centrosome

• The centrosome is located in the cytoplasm usually close to the nucleus.

• It consists of two centrioles — oriented at right angles to each other — embedded in a mass of amorphous material containing more than 100 different proteins.

• It is duplicated during S phase of the cell cycle.

• Just before mitosis, the two centrosomes move apart until they are on opposite sides of the nucleus.

• As mitosis proceeds, microtubules grow out from each centrosome with their plus ends growing toward the metaphase plate. These clusters of microtubules are called spindle fibers.

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• Centrosomes are the microtubule organizing centers

• Centrioles: bundles of microtubules

• Centrioles composed mainly of tubulin are built from a

cylindrical bundle of 27 microtubules arranged in nine triplets.

Centrosomes and Centrioles Centrosomes and Centrioles

Figure 3-8a,c: Centrioles, cilia, and flagella

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• Motor proteins

• 2:9 microtubule pattern

• Cilia move fluids

• Flagella move sperm cell

Cilia and Flagella

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Extracellular Matrix Extracellular Matrix

• Extracellular material that is synthesized and secreted by the cells of a tissue.

• Composed of Proteoglycans (glycoproteins or proteins covalently bound to

polysaccharide chains) and Insoluble

protein fibers such as collagen, fibronectin, laminin, fibrillin and elastin.

• It provides strength and helps anchor cells to the Matrix

• Attachments between the ECM and

proteins in cell membrane or cytoskeleton

are one means of communication between

cell and environment

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Proteoglycans Proteoglycans

• Proteoglycans are glycoproteins that are heavily glycosylated.

The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan (GAG) chain(s).

• The point of attachment is a Ser residue to which the

glycosaminoglycan is joined through a tetrasaccharide bridge (For example: chondroitin sulfate-GlcA-Gal-Gal-Xyl-PROTEIN).

• The Ser residue is generally in the sequence -Ser-Gly-X-Gly- (where X can be any amino acid residue), although not every protein with this sequence has an attached glycosaminoglycan.

• The chains are long, linear carbohydrate polymers that are negatively charged under physiological conditions, due to the occurrence of sulfate and uronic acid groups. Proteoglycans occur in the connective tissue.

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Cell Membrane Proteins Cell Membrane Proteins

• Cell Adhesion Molecules (CAMS)-

Membrane spanning proteins responsible for cell junctions and transient cell

adhesions. Include Claudins, Occludins, Cadherins, Integrins and Selectins

• Cell-Cell and Cell-Matrix Adhesions are

mediated by these Cell Adhesion Molecules

• Growing nerve cells move along ECM with help of nerve cell adhesion molecules

(NCAM’s)

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Cell Adhesion Molecules (CAM’s) Cell Adhesion Molecules (CAM’s)

• Attachments between ECM and Cell

Membrane Proteins or Cytoskeleton are a

means of communication between a cell

and its external environment

(51)

• Tissue defined: A collection of cells usually held together by cell junctions that works together to achieve a common purpose

• Amount of Extracellular Matrix in a tissue is highly variable

• Tissue types

• Epithelial

• Connective

• Muscle

Primary Tissue Types

(52)

Different epithelial cells/tissues and their appearance

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Epithelial Tissues

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Epithelial Tissue Epithelial Tissue

• Protects the internal environment of the body and regulates exchange of materials between the internal and external

environment

• Five Functional Types: Exchange,

Transporting, Ciliated, Protective and

Secretory

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• Leaky junctions

• Rapid transport

• Oxygen

• Carbon dioxide

• Ions & fluids

• Capillaries

• Lung alveoli

Exchange Epithelial Tissues Exchange Epithelial Tissues

Figure 3-18a: Movement of substances across tight and leaky epithelia

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• Transport epithelium

• Intestinal microvili

• Tight junctions

• Ciliated epithelium

• Trachea

• Sweep mucous out

• Protective epithelium

• Skin

• Multiple cell More Epithelia

More Epithelia

Figure 3-18b: Movement of substances across tight

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• Ciliated epithelium

• Trachea

• Sweep mucous out

• Protective epithelium

• Skin

• Multiple cell layers

• Prevent exchange More Epithelia More Epithelia

Figure 3-19a: Ciliated epithelia

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• Exocrine tissues

• Mucous glands- goblet cells

• Sweat glands

• Secreted externally

• Endocrine tissues

• Hormones

• Secreted to ECF & blood Secretory Epithelia

Secretory Epithelia

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Secretory Epithelia Secretory Epithelia

Figure 3-20: Goblet cells

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Connective Tissue Connective Tissue

• Provides structural support and sometimes physical barriers that along with

specialized cells helps defend the body from foreign invaders.

• The distinguishing characteristic is an

extracellular matrix with widely scattered cells that secrete and modify the matrix.

Blood, cartilage, bone, support tissues for skin and organs

• ECM of Connective Tissue is a ground

substance of proteoglycans and water in

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Connective Tissue Connective Tissue

• Loose Connective Tissue: Underlies skin and provides support for small glands

• Dense Connective Tissue: Provides

strength and flexibility- ligaments, tendons

and muscle sheaths

(63)

• Matrix

• Fibers & their functions

• Fibroblast cells

• Collagen

• Elastin

• Fibrillin

• Fibronectin

Connective Tissues (CT)

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Connective Tissues (CT) Connective Tissues (CT)

Figure 3-22: Cells and fibers of connective tissue

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• Dense

connective tissue

• Tendons &

ligaments

• Collagen dominates

More Connective Tissues

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More Connective Tissues More Connective Tissues

• Adipose connective tissue

• Adipocytes

• Fat vacuoles

• Blood

• Plasma matrix

• Free blood cells

(69)

Supporting Connective Tissues

(70)

Muscle and Nerve Muscle and Nerve

• Have very little Extracellular Matrix

• Muscle has the ability to contract and produce force and movement

• Neural tissue has two types:

Neurons- Carry information in the form of chemical and electrical

signals from one part of the body to

another Glial cells or Neuroglia- Provide support for

neurons.

(71)

• Contractile

• Force

• Movement

• Excitable- they conduct signals

• Types

• Cardiac

• Smooth

Muscle Tissues

(72)

• Neurons send signals

• Excitable

• Electrical

• Chemical

• Glial cells support Nervous Tissues

Nervous Tissues

Figure 8-2: Model neuron

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• Necrosis

• Damaged cells die

• Disrupt/kill neighbors

• Apoptosis

• Normal cell replacement

• Programmed cell death

• Does not damage neighbors

• Stem cells

• Role in cell replacement

Cell Life, Death, and Replacement

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Apoptosis Apoptosis

• Apoptosis is a naturally occurring process by which a cell is directed to Programmed Cell Death.

Apoptosis is based on a genetic program that is an indispensable part of the development and function of an organism. In this process, cells that are no

longer needed or that will be detrimental to an organism or tissue are disposed of in a neat and orderly manner; this prevents the development of an inflammatory response, which is often associated with Necrotic cell death. There are at least two

broad pathways that lead to Apoptosis, an

"Extrinsic" and an "Intrinsic" Pathway. In both pathways, signaling results in the activation of a

family of Cys (Cysteine) Proteases, named Caspases that act in a proteolytic cascade to dismantle and remove the dying cell.

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The role of caspase

• During apoptosis, the cell is killed by a class of proteases called caspases. More than 10 caspases have been

identified. Some of them (e.g., caspase 8 and 10) are involved in the initiation of apoptosis, others (caspase 3, 6, and 7) execute the death order by destroying essential proteins in the cell. The apoptotic process can be

summarized as follows:

1. Activation of initiating caspases by specific signals 2. Activation of executing caspases by the initiating

caspases which can cleave inactive caspases at specific sites.

3. Degradation of essential cellular proteins by the executing caspases with their protease activity.

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Adapted Cell + Stress

Injury Normal

cell

Reversibly injured cell

Irreversibly

Injured cell Dead cell

+Stress

Apoptosis Necrosis - Stress

- Stress

Overview

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Adapted Cell + Stress

Normal

cell - Stress

Cellular adaptation

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Adapted Cell +Stress

Normal cell

Stress = ?

Increased/decreased workload

* skeletal muscle and body building

* cardiac muscle and hypertension

* skeletal muscle disuse (limb immobilization)

Increased/decreased stimulation

* estrogenic stimulation of uterus in pregnancy - Stress

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Adapted Cell

Cellular adaptations to stress

1. Hyperplasia (more cells) 2. Hypertrophy (bigger cells) 3. Atrophy (smaller cells)

4. Metaplasia (different type of cells)

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1. Hyperplasia 1. Hyperplasia

(more cells) (more cells) 1. Physiologic

1. Physiologic

* Hormonal (breast/uterus in pregnancy)

* Compensatory (liver after partial hepatectomy)

2. Pathologic 2. Pathologic

Excessive hormone/GF stimulation of target tissue

* Endometrial hyperplasia (x’s estrogen)

* Benign prostatic hyperplasia (x’s androgens)

(98)

Thyroid hyperplasia

(99)

Hyperplasia Hyperplasia

(Mechanism) Cell proliferation

via increased production of TRANSCRIPTION FACTORS

due to

* Increased production of GF

* Increased levels of GF receptors

* Activation of intracellular signaling

(100)

Adapted Cell

2. Hypertrophy (larger cells)

*

Not due to swelling

* Increased synthesis of structural components

* Results in larger organ

* May occur with hyperplasia

(101)

Hypertrophy (Heart)

(102)

Hypertrophy of uterus

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3. Atrophy

(smaller cells) 1. Physiologic

During development: i.e. notochord; thyroglossal duct

2. Pathologic

(local or generalized) via

* disuse * Loss of endocrine stimulation

* denervation * Aging

* ischemia * Pressure

* Nutrition

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Normal Atrophied Brain atrophy

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Atrophy

(Mechanism)

Reduction in structural components

Decreased number of mito, myofilaments, ER via

proteolysis (lysosomal proteases; ubiquitin-proteosome system)

Increase in number of autophagic vacuoles

Residual bodies (i.e. lipofuscin  brown atrophy) NB: diminished function but not dead

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4. Metaplasia

One adult cell type replaces another

Reversible

Columnar to squamous epithelium (most common epithelial type of metaplasia)

Chronic irritation i.e. (in trachea and bronchi of smokers) Vit A deficiency squamous metaplasia in respiratory epithelium

May be some loss of function

(110)

Photomicrograph of the trachea from a smoker. Note that the columnar ciliated epithelium has been replaced by squamous epithelium.

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Metaplasia

(Mechanism) Reprogramming

1. of stem cells present in normal tissues 2. of undifferentiated mesenchymal cells

in connective tissue Mediated by signals from

cytokines, GF or ECM

Leading to induction of specific transcription

factors

(113)

Metaplasia versus Dysplasia

1. Dysplasia is a pathological term used to refer to an irregularity that hinders cell maturation within a particular tissue whereas Metaplasia is the process of the reversible substitution of a distinct kind of cell with another mature cell of the similar distinct kind.

2. Dysplasia is cancerous whereas Metaplasia is non-cancerous.

3. Metaplasia can be stopped by removing the abnormal stimulus, but Dysplasia is a non-reversible process.

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• Organ defined: A group of tissues that carries out related functions

• Skin

• Epidermal tissue

• Multiple cell layers

• Keritin: hardened

• Desmosomes: junctions holding cells together

Organs:

Focus on the Skin, the Body’s Largest Organ Organs:

Focus on the Skin, the Body’s Largest Organ

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Functions of skin Functions of skin

• Protection

• Cushions and insulates and is waterproof

• Protects from chemicals, heat, cold, bacteria

• Screens UV

• Synthesizes vitamin D with UV

• Regulates body heat

• Prevents unnecessary water loss

• Sensory reception (nerve endings)

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Remember…

• Four basic types of tissue

• Epithelium – epidermis

• Connective tissue - dermis

• Muscle tissue

• Nervous tissue

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Epidermis Epidermis

• Keratinized stratified squamous epithelium

• Four types of cells

• Keratinocytes – deepest, produce keratin (tough fibrous protein)

• Melanocytes - make dark skin pigment melanin

• Merkel cells – associated with sensory nerve endings

• Langerhans cells – macrophage-like dendritic cells

• Layers (from deep to superficial)

• Stratum basale or germinativum – single row of cells attached to dermis; youngest cells

• Stratum spinosum – spinyness is artifactual;

tonofilaments (bundles of protein) resist tension

• Stratum granulosum – layers of flattened keratinocytes producing keratin (hair and nails made of it also)

• Stratum lucidum (only on palms and soles)

• Stratum corneum – horny layer (cells dead, many layers thick)

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Epithelium: layers (on left) and cell types (on right)

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Dermis Dermis

• Strong, flexible connective tissue: your

“hide”

• Cells: fibroblasts, macrophages, mast cells, WBCs

• Fiber types: collagen, elastic, reticular

• Rich supply of nerves and vessels

• Critical role in temperature regulation (the vessels)

• Two layers (see next slides)

• Papillary – areolar connective tissue; includes dermal papillae

• Reticular – “reticulum” (network) of collagen and reticular fibers

(121)

*

Dermis layers

*

Dermal papillae

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Hypodermis Hypodermis

• “Hypodermis” (Gk) = below the dermis

• “Subcutaneous” (Latin) = below the skin

• Also called “superficial fascia”

“fascia” (Latin) =band; in anatomy: sheet of connective tissue

• Fatty tissue which stores fat and anchors skin (areolar tissue and adipose cells)

• Different patterns of accumulation

(male/female)

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Burns Burns

• First degree- Epidermis appears red (erythema). Dry texture.

Painful. 1wk or less to heal

• Second degree (superficial partial thickness) Extends into

superficial (papillary) dermis- Appears red with clear blisters.

Blanches with pressure. Moist texture. Painful . 2-3wks to heal. Complications-Local infection/cellulitis

• Second degree (deep partial thickness) Extends into deep

(reticular) dermis. Appears red-and-white with bloody blisters.

Less blanching. Moist texture. Painful. Weeks to heal - may progress to third degree burn. Can cause scarring,

contractures (may require excision and skin grafting)

• Third degree (full thickness). Extends through entire dermis.

Stiff and white/brown appearance. Dry, leathery texture.

Painless. Requires excision. Complications- Scarring, contractures, amputation

• Fourth degree Extends through skin, subcutaneous tissue and

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• Dermal tissues

• Loose CT

• Fibers & muscles

• Hair, sweat glands

• Sebaceous glands

• Hypodermal tissues

• Blood vessels

• Nerves

• Adipose & loose CT More on Skin

More on Skin

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Chapter 3Chapter 3

H UMAN P HYSIOLOGY H UMAN P HYSIOLOGY

Chapter 3 Chapter 3

Cells and Tissues

About this Chapter About this Chapter

• Cell structure and types

• Cell differentiation

• Compartmentalization

• Mechanical properties and cell functions

• Cell junctions

• Tissue types and characteristics

Overview: Cells to Organ Systems

Overview: Cells to Organ Systems

• Cytosol

• Organelles

• Inclusion

• Dissolved

• Insoluble Cell Cytoplasm Cell Cytoplasm

Nonmenbranous Organelles

Nonmenbranous Organelles

Nonmenbranous Organelles Nonmenbranous Organelles

• Internal lumen and membranes for protected reactions

• Mitochondria: Generates cell energy (ATP) , have DNA

Membranous Organelles: Create cell compartments

Membranous Organelles: Create cell compartments

• Smooth ER: Lipid synthesis & conversion

• Rough ER: Ribosomes, protein assembly &

transport vesicles

Endoplasmic Reticulum (ER) ad Ribosomes

Endoplasmic Reticulum (ER) ad Ribosomes

• Protein packaging

• Secretory vesicles

• Secreted to E C F Golgi Apparatus

Golgi Apparatus

Golgi Apparatus Golgi Apparatus

• Lysosomes

• Enzymes

• Intracellular digestion

• Peroxisomes

• Hydrogen peroxide

• Detoxification

• Fatty acid degradation Cytoplasmic Vesicles Cytoplasmic Vesicles

• Nuclear envelope

• Nuclear pore complex

• Chromatin

• DNA form genes

• Nucleoli

• DNA concentrations

• Control rRNA synthesis Nucleus

Nucleus

Nucleus Nucleus

Nuclear Envelope- Double Phospholipid Bilayer

Nuclear Envelope- Double Phospholipid Bilayer

Overview: Cells to Organ Systems Overview: Cells to Organ Systems

Cell Membrane

Cell Membrane

The importance of selectively permeable membranes

Cell Junctions:

Cell Junctions:

• Gap Junctions: Simplest Cell-Cell Junction.

Can open and close. Present in many tissues. Proteins associated with:

Connexins

• Tight Junctions: Cell-Cell Junction in

Epithelial tissue that does not allow much movement of material between cells.

Proteins associated with: Claudins and Occludins. Blood Brain Barrier

• Anchoring Junctions: Attach cells to each

other (cell-cell anchoring junction) or to the

ECM (cell-matrix anchoring junction).

Junctions Junctions

Key Junction Proteins:

Connexin, cadherins, occludin & integrins Key Junction Proteins:

Connexin, cadherins, occludin & integrins

Intracellular Proteins Intracellular Proteins

• Tubulin (microtubules)

• Actin- (microfilaments)

• Myosin (intermediate filaments)

• Keratin (intermediate filaments)

• Neurofilament protein

• Kinesin

• Dynein

H ^UMAN P ^HYSIOLOGY H ^UMAN P ^HYSIOLOGY