Chapter 3 - Compartmentation: Cells and Tissues

Functional Compartments of the Body

• Three major cavities:
  • Cranial
  • Thoracic
  • Abdominopelvic
• Fluid-filled compartments:
  • Circulatory system
  • Eyes
  • Cerebrospinal fluid (CSF)
  • Pleural and pericardial sacs

Body Compartments - Anatomical: The Body Cavities

• Anterior vs. Posterior
  • Cranial cavity
  • Thoracic cavity
  • Pleural sac
  • Pericardial sac
  • Diaphragm
  • Abdominal cavity
  • Abdominopelvic cavity
  • Pelvic cavity

The Lumens of Some Organs Are Outside the Body

• Hollow organs include heart, lungs, blood vessels, and intestines.
• Lumen is the interior of any hollow organ.
  • May be wholly or partially filled with air or fluid.
  • For some organs, it's an extension of the external environment.

Functionally, the Body Has Three Fluid Compartments

• Extracellular fluid (ECF)
  • Plasma
  • Interstitial fluid
• Intracellular fluid (ICF)

Body Compartments - Functional: Body Fluid Compartments

• Extracellular fluid (ECF) lies outside the cells.
  • Blood plasma is the extracellular fluid inside blood vessels.
  • Interstitial fluid surrounds most cells.
• Cells (intracellular fluid, ICF) subdivide into intracellular compartments.
• Examples of cell sizes:
  • Fat cell: 50-150 \mu m
  • Ovum: 100 \mu m
  • Red blood cell: 7.5 \mu m
  • White blood cell: 15 \mu m
  • Smooth muscle cell: 15-200 \mu m long

Body Compartments – Compartments Are Separated by Membranes

• Pericardial sac surrounds the heart.
• Tissue membranes have many cells.
• Pericardial membrane: layer of flattened cells supported by connective tissue.
• Each cell of the pericardial membrane has a cell membrane.
• Phospholipid bilayers create cell membranes.
• Cell membrane is a phospholipid bilayer.

Biological Membranes

• The cell membrane separates the cell from the environment.
  • Physical isolation
  • Regulation of exchange with the environment
  • Communication between the cell and its environment
  • Structural support
  • Secretion: cell releases substance into extracellular space
• Membranes are mostly lipid and protein.
  • Fluid mosaic model

Composition of Selected Membranes

• Table of membrane composition:
  • Red blood cell membrane: Protein (49%), Lipid (43%), Carbohydrate (8%)
  • Myelin membrane around nerve cells: Protein (18%), Lipid (79%), Carbohydrate (3%)
  • Inner mitochondrial membrane: Protein (76%), Lipid (24%), Carbohydrate (0%)

The Cell Membrane The Fluid Mosaic Model of Biological Membranes

• Illustration of membrane components

Membrane Lipids Create a Hydrophobic Barrier

• Lipids:
  • Phospholipids
  • Sphingolipids
  • Cholesterol
• Phospholipid structures in aqueous solutions:
  • Bilayer
  • Micelle
  • Liposome

Membrane Lipids Create a Hydrophobic Barrier

• Lipids:
  • Phospholipids
  • Sphingolipids
  • Cholesterol
• Phospholipid structures in aqueous solutions:
  • Bilayer
  • Micelle
  • Liposome

Membrane Lipids Create a Hydrophobic barrier

• Structure of Sphingolipid
  • Sphingosine
  • Fatty acid (N-acyl chain)
  • Substituent (R)
  • Categories:
  • Ceramides
  • Sphingomyelins
  • Glycosphingolipids
  • Cerebrosides
  • Lactosylceramides
  • Gangliosides
  • Sulfatides

Membrane Lipids Create a Hydrophobic Barrier

• Lipids:
  • Phospholipids
  • Sphingolipids
  • Cholesterol
• Phospholipid structures in aqueous (solvent = water) solutions:
  • Bilayer
  • Micelle
  • Liposome

The Cell Membrane Membrane Phospholipids

• Membrane phospholipids form bilayers, micelles, or liposomes.
  • They arrange themselves so that their nonpolar tails are not in contact with aqueous solutions.
• Structures:
  • Phospholipid bilayer forms a sheet.
  • Polar head (hydrophilic)
  • Nonpolar fatty acid tail (hydrophobic)
  • Micelles are droplets of phospholipids, important in lipid digestion.
  • Liposomes have an aqueous center.
  • Immunoliposomes

Membrane Proteins May Be Loosely or Tightly Bound to the Membrane

• Proteins:
  • Integral vs. Peripheral
  • Transmembrane
  • Lipid-anchored
  • GPI anchor
• Lipid rafts:
  • Made up of sphingolipids and lipid-anchored proteins

The Cell Membrane Concept Map of Cell Membrane Components

• Diagrammatic representation

Lipid rafts are made of sphingolipids

• Illustration

Membrane Carbohydrates Attach to Both Lipids and Proteins

• Glycocalyx
  • Only on the external surface of the cell
  • Protective layer
  • Formed by:
  • Glycolipids
  • Glycoproteins

ABO blood group system

• Antigens and Antibodies
  • A antigen
  • B antigen
  • A and B antigens
  • None

Intracellular Compartments

• Differentiation: selected genes are active to lead to specialized cell
• Cells are divided into compartments
• Cell Membrane
• Cytoplasm
  • Cytosol
  • Inclusions
  • Cytoskeleton – insoluble protein fibers
  • Organelles
• Nucleus

Cell Structure

• The Cell is composed of:
  • Cell membrane
  • Nucleus
  • Cytoplasm
  • Cytosol
    • Fluid portion of cytoplasm
  • Membranous organelles
    • Mitochondria
    • Endoplasmic reticulum
    • Golgi apparatus
    • Lysosomes
    • Peroxisomes
  • Inclusions
    • Lipid droplets
    • Glycogen granules
  • Protein fibers
    • Cytoskeleton
    • Centrioles
    • Cilia
    • Flagella
• Extracellular Fluid

Inclusions Are in Direct Contact with the Cytosol

• Lack membranes
• Nutrient storage
  • Glycogen granules
  • Lipid Droplets
• Non-nutrient storage function
  • Ribosomes
  • Made from protein or RNA and protein
  • Manufacture proteins
  • Fixed vs. free ribosomes
  • Polyribosomes

Cytoplasmic Protein Fibers Come In Three Sizes

• Microfilaments
  • Actin fibers
• Intermediate filaments
  • Keratin
  • Neurofilament
• Microtubules
  • Tubulin
• Associated accessory proteins
• Involved in structural support and cell movement with motor proteins

Diameter of Protein Fibers in the Cytoskeleton

• Table of fiber diameters and functions:
  • Microfilaments: Diameter 7 nm, Protein Actin (globular), Function Cytoskeleton; associates with myosin for muscle contraction
  • Intermediate Filaments: Diameter 10 nm, Protein Keratin, neurofilament protein (filaments), Function Cytoskeleton, hair and nails, protective barrier of skin
  • Microtubules: Diameter 25 nm, Protein Tubulin (globular), Function Movement of cilia, flagella, and chromosomes; intracellular transport of organelles; cytoskeleton

Cell Structure

Cytoskeleton

• Microvilli increase cell surface area, supported by microfilaments.
• Microfilaments form a network just inside the cell membrane.
• Microtubules are the largest cytoskeleton fiber.
• Intermediate filaments include myosin and keratin.

Microtubules Form Centrioles, Cilia, and Flagella

• Centrosome
  • Assembles tubulin monomers into microtubules
• Centrioles
  • Direct DNA movement in cell division
• Cilia (cilium)
  • Fluid movement across cells
• Flagella (flagellum)
  • Cell (sperm) movement through fluid

Cilia and flagella

• Structure and function
• Cilia on the surface of respiratory epithelium
• Cilia and flagella have 9 pairs of microtubules surrounding a central pair.
• Beating of cilia and flagella creates fluid movement.

The Cytoskeleton Is a Changeable Scaffold

• Cytoskeleton functions:
  • Cell shape
  • Internal organization
  • Intracellular transport
  • Assembly of cells into tissues
  • Movement

Motor Proteins Create Movement

• Use ATP to create movement along cytoskeletal proteins
• Myosins
  • Muscle contraction
• Kinesins and dyneins
  • Movement of vesicles along microtubules
• Dyneins
  • Movement of cilia and flagella

Motor proteins

• Illustration of motor protein moving an organelle along a cytoskeletal fiber using ATP.

Organelles Create Compartments for Specialized Functions

• One or more phospholipid membranes
• Mitochondria with mitochondrial matrix, mitochondrial DNA, and intermembrane space
  • Essential role in cellular ATP production
• The Endoplasmic reticulum (ER)
  • Rough endoplasmic reticulum (RER)
  • Synthesis of proteins
  • Smooth endoplasmic reticulum (SER)
  • Synthesis of fatty acids, steroids, lipids
• The Golgi apparatus or Golgi complex
  • Sorts, modifies and packages proteins into vesicles
• Vesicles - storage vs. secretory vesicles
  • Lysosomes –break down bacteria and old organelles
  • Peroxisomes –break down fatty acids and toxic materials

Cell Structure

Organelles

• Mitochondria: Double-walled organelles with inner matrix, cristae, and intermembrane space for ATP production.
• Golgi Apparatus and Vesicles: Hollow curved sacs (cisternae) surrounded by vesicles for protein modification and packaging.
• Endoplasmic Reticulum (ER) and Ribosomes: Network of interconnected membrane tubes; Rough ER (with ribosomes) for protein synthesis, Smooth ER (without ribosomes) for lipid synthesis and calcium storage.

Cell Structure

Perioxisomes, Lysosomes, Centrioles

• Peroxisomes: Contain enzymes that break down fatty acids and some foreign materials.
• Lysosomes: Small, spherical storage vesicles that contain powerful digestive enzymes.
• Centrioles: Made from microtubules and direct DNA movement during cell division.

The Nucleus Is the Cell’s Control Center

• Nuclear envelope: two membranes with pores
• Nuclear pore complexes
• Chromatin: DNA and associated proteins
• Nucleoli (nucleolus)
  • Control synthesis of ribosomal RNA

Cell Structure

Nucleus

• Surrounded by a double-membrane nuclear envelope with pores for communication with the cytoplasm.
• Contains randomly scattered granular material composed of DNA and proteins (chromatin).
• Nucleoli are dark-staining bodies of DNA, RNA, and protein.

Protein synthesis demonstrates subcellular compartmentation.

• Illustration of protein synthesis pathway, including:
  • mRNA transcription from DNA in the nucleus
  • mRNA transport to cytosolic ribosomes for protein synthesis
  • Protein targeting to specific organelles or secretion

Tissues of the Body

• Histology – study of tissue structure and function
• Extracellular matrix has many functions
  • Synthesized and secreted by cells
  • Composition varies from tissue to tissue
  • Proteoglycans
  • Glycoproteins
  • Insoluble protein fibers
  • Collagen, fibronectin, laminin

Cell Junctions Hold Cells Together to Form Tissues

• Cell junctions
• Cell-adhesion molecules (CAMs) – membrane-spanning proteins
• Gap junctions - communicating junctions
• Tight junctions - occluding junctions Anchoring junctions
  • Paracellular pathway
  • Cell-cell with cadherins
  • Adherens junctions
  • Desmosomes
  • Cell-matrix with integrins
  • Hemidesmosomes
  • Focal adhesions

Major Cell Adhesion Molecules (CAMS)

• Table of major CAMs:
  • Cadherins: Cell-cell junctions (adherens junctions, desmosomes). Calcium-dependent.
  • Integrins: Primarily in cell-matrix junctions. Function in cell signaling.
  • Immunoglobulin superfamily CAMs: NCAMS (nerve-cell adhesion molecules). Nerve cell growth during nervous system development.
  • Selectins: Temporary cell-cell adhesions.

Cell Junctions

• Categories: Communicating, Occluding, Anchoring
• Location: Cell-cell junctions, Cell-matrix junctions
• Types:
  • Gap junction: Membrane protein Connexin. Cytoskeleton fiber - None.
  • Tight junction: Membrane protein Claudin, occludin. Cytoskeleton fiber - None.
  • Adherens junction: Membrane protein Cadherin. Cytoskeleton fiber Actin.
  • Desmosome: Membrane protein Cadherin. Cytoskeleton fiber Intermediate filaments (Keratin).
  • Focal adhesion: Matrix Protein Fibronectin and other proteins. Cytoskeleton fiber Actin.
  • Hemidesmosome: Matrix Protein Laminin. Cytoskeleton fiber Keratin (intermediate filaments).

Cell Junctions

• Communicating junctions allow direct cell to cell communication.
  • Heart muscle has gap junctions that allow chemical and electrical signals to pass rapidly from one cell to the next.
  • Connexin proteins form gap junctions.

Cell Anchoring Junctions

• Communicating junctions: Allow direct cell-to-cell communication through connexin proteins.
• Occluding junctions: Block movement of material between cells via claudin and occludin proteins (Tight junctions).
• Anchoring junctions: Hold cells to one another and to the extracellular matrix.

What happens when the anchoring junctions disappear?

• Cancer cells lose their anchoring junctions
  • Secrete proteases (MMPs)
  • Metastasize
• Normal cell junctions destroyed
  • Autoimmune disease
  • Pemphugus vulgaris

Disturbing images

• Image relating to described disease

Pemphugus Vulgaris

• Medical case examples

Four Tissue Types

• Epithelial
• Connective
• Muscle
• Neural/nerve

Epithelia Provide Protection and Regulate Exchange

• Epithelial tissues = epithelia
• Structure of epithelia
  • One or more layers of epithelial cells
  • Separated from underlying tissue by basal lamina (basement membrane)
  • Tight vs. leaky epithelia

Epithelial Tissue

• Most epithelia attach to an underlying matrix layer called the basal lamina or basement membrane.
• Epithelial cells attach to the basal lamina using cell adhesion molecules.
• Basal lamina (basement membrane) is an acellular matrix layer that is secreted by the epithelial cells.

Epithelial Tissue

Five Functional Categories of Epithelia

• Exchange: One layer, Flattened cells, Pores between cells permit easy passage of molecules (Lungs, lining of blood vessels)
• Transporting: One layer, Columnar or cuboidal cells, Tight junctions prevent movement between cells; surface area increased by folding of cell membrane into fingerlike microvilli (Intestine, kidney, some exocrine glands)
• Ciliated: One layer, Columnar or cuboidal cells, One side covered with cilia to move fluid across surface (Nose, trachea, and upper airways; female reproductive tract)
• Protective: Many layers, Flattened in surface layers; polygonal in deeper layers, Cells tightly connected by many desmosomes (Skin and lining of cavities that open to the environment)
• Secretory: One to many layers, Columnar or polygonal cells, Protein-secreting cells filled with membrane-bound secretory granules and extensive RER; steroid-secreting cells contain lipid droplets and extensive SER (Exocrine glands, including pancreas, sweat glands, and salivary glands; endocrine glands, such as thyroid and gonads)

Epithelial Tissue

• Functional connections in human body

Types of Epithelia (Histology)

• Structurally classification
  • Sheets of tissue that cover surfaces or line hollow organs & tubes
  • Secretory epithelia synthesize and release substances
• Histologically classified by layers and cell shapes
  • Layers: simple & stratified
  • Shapes: squamous, cuboidal, & columnar

Exchange Epithelium

• Very thin, flattened cells
• Allow gas exchange
• Line the blood vessels and lungs
• Classified as simple squamous epithelium
• Called endothelium in the heart and blood vessels

Types of Epithelia

Exchange Epithelium

• Thin, flat cells allow movement through and between the cells.
• Capillary epithelium example.

Transporting Epithelium

• Cell shape - cuboidal or columnar
• Membrane modifications
  • Apical membrane: faces lumen
  • Basolateral membrane: faces ECM
• Cell junctions
• Cell organelles - many mitochondria
• Properties
  • differ depending on where the epithelium is found
  • can be regulated and modified in response to stimuli

Types of Epithelia

Transporting Epithelium

• Selectively move substances between a lumen and the ECF.
• Apical membrane and Basolateral membrane
• Tight junctions prevent movement between adjacent cells.

Ciliated and Protective Epithelia

• Cilia move fluid and particles in respiratory system and female reproductive tract
• Protective epithelia
  • prevent exchange
  • protect areas subject to mechanical and chemical stress

Types of Epithelia

Ciliated Epithelium

• Beating cilia create fluid currents that sweep across the epithelial surface.
• SEM of the epithelial surface of an airway

Types of Epithelia

Protective Epithelium

• Protective epithelia have many stacked layers of cells that are constantly being replaced.
• Section of skin showing cell layers.

Secretory Epithelia

• Produce and secrete a substance into the extracellular space
• May be scattered or grouped into glands
• Exocrine glands: release products to external environment (most through ducts)
  • Serous secretions
  • Mucous secretions (mucus)
  • Goblet cells - single exocrine cells that produce mucus
• Endocrine glands: release hormones into extracellular compartments

Types of Epithelia

Secretory Epithelium

• Secretory epithelial cells make and release a product.
• Exocrine secretions, such as mucus, are secreted outside the body.
• Secretions of endocrine cells (hormones) are released into the blood.
• TEM of goblet cell

Development of endocrine and exocrine glands

• During development, the region of epithelium destined to become glandular tissue divides downward into the underlying connective tissue.
• A hollow center, or lumen, forms in exocrine glands, creating a duct that provides a passageway for secretions to move to the surface of the epithelium.
• Endocrine glands lose the connecting bridge of cells that links them to the parent epithelium. Their secretions go directly into the bloodstream.

Characteristics of the Four Tissue Types

• Table summarizing characteristics of Epithelial, Connective, Muscle, and Nerve tissues, including:
  • Matrix Amount
  • Matrix Type
  • Unique Features
  • Surface Features of Cells
  • Locations
  • Cell Arrangement and Shapes

Structure of Connective Tissues

• Ground substance (matrix)
  • Highly variable
• Connective tissue cells in ECM
  • Fixed cells – local maintenance, tissue repair, energy storage
  • -blasts - example: flbroblasts
  • -clasts
  • -cytes
  • Mobile cells - defense
• Matrix fibers
  • Collagen, elastin, fibrillin, fibronectin

Connective Tissue

Map of Connective Tissue Components

• Mobile Blood cells
• Fixed
• Matrix
  • Ground Substance
  • Protein Fibers

Connective Tissue

Types of Connective Tissue

• Loose connective tissue: Gel; more ground substance than fibers or cells (Skin around blood vessels and organs, under epithelia)
• Dense, irregular connective tissue: More fibers than ground substance (Muscle and nerve sheaths)
• Dense, regular connective tissue: More fibers than ground substance (Tendons and ligaments)
• Adipose tissue: Very little ground substance (Depends on age and sex)
• Blood: Aqueous (In blood and lymph vessels)
• Cartilage: Firm but flexible; Collagen (Joint surfaces, spine, ear, nose, larynx)
• Bone: Rigid due to calcium salts (Bones)

Connective Tissues Provide Support and Barriers

• Types of Connective Tissue
  • Loose connective tissues
  • Elastic tissues under skin
  • Provide support for small glands
  • Dense connective tissues
  • Irregular and regular
  • Provide strength or flexibility
  • Tenons – skeltal muscles to bone
  • Ligaments – bone to bone

Connective Tissues Provide Support and Barriers

• Types of Connective Tissue (continued)
  • Supporting connective tissues
  • Cartilage
    • Nose, ears, knee, windpipe/trachea
    • Lacks blood supply
  • Bone
    • Calcified
  • Adipose Tissue
    • Adipocytes (fat cells)
    • White fat vs. brown fat
  • Blood
    • Plasma, blood cells, and cell fragments

Types of Connective Tissue

Loose Connective Tissue

• Very flexible, with multiple cell types and fibers.
• Collagen fibers, Fibroblasts, Elastic fibers, Ground substance, Free macrophage

Types of Connective Tissue

Bone and Cartilage

• Hard bone forms when osteoblasts deposit calcium phosphate crystals in the matrix.
• Cartilage has firm but flexible matrix secreted by cells called chondrocytes.

Types of Connective Tissue

Dense Connective Tissue

• Collagen fibers of tendon are densely packed into parallel bundles.
• Tendons connect muscle to bone and ligaments attach bone to bone

Bridge-enhanced ACL repair (BEAR) grafts

• Orthop J Sports Med. 2016;4(11):2325967116672176. SAGE Publishing.

Bridge-enhanced ACL repair (BEAR) grafts

• Orthop J Sports Med. 2016;4(11):2325967116672176. SAGE Publishing.
• Results: There were no joint infections or signs of significant inflammation in either group. There were no differences between groups in effusion or pain, and no failures by Lachman examination criteria (BEAR, 8 grade A and 2 grade B; ACL reconstruction, 10 grade A).
• Magnetic resonance images from all of the BEAR and ACL-reconstructed patients demonstrated a continuous ACL or intact graft.
• In addition, hamstring strength at 3 months was significantly better in the BEAR group than in the hamstring autograft group (mean ± SD: 77.9\% \pm 14.6\% vs 55.9\% \pm 7.8\% of the contralateral side; P < .001).

Types of Connective Tissue

Blood and Adipose Tissue

• Blood consists of liquid matrix (plasma) plus red and white blood cells and the cell fragments called platelets.
• In white fat, the cell cytoplasm is almost entirely filled with lipid droplets.

Muscle and Neural Tissues are Excitable

• Muscle tissue
  • Contractile
  • Force and movement
  • Three types
  • Cardiac, Smooth, & Skeletal
• Neural tissue
  • Neurons (nerve cells) send signals
  • Excitable
  • Glial cells (neuroglia) provide support

Characteristics of the Four Tissue Types

• Table summarizing characteristics of Epithelial, Connective, Muscle, and Nerve tissues, including:
  • Matrix Amount
  • Matrix Type
  • Unique Features
  • Surface Features of Cells
  • Locations
  • Cell Arrangement and Shapes

Tissue Remodeling

• Cell death
  • Necrosis (death from injury)
  • Apoptosis (programmed cell death, cell suicide)
• Stem cells
  • Mitosis
  • Totipotent, pluripotent, multipotent
  • Plasticity

Organs

• Groups of tissues with related function
• Skin as an example of an organ
  • Incorporates all four tissue types
  • Multiple functions

The Skin

The Layers of the Skin

• Epidermis consists of multiple cell layers that create a protective barrier.
• The dermis is loose connective tissue that contains exocrine glands, blood vessels, muscles, and nerve endings.
• Hypodermis contains adipose tissue for insulation.
• Sweat glands secrete a dilute salt fluid to cool the body.
• Apocrine glands in the genitalia, anus, axillae (axilla, armpit), and eyelids release waxy or viscous milky secretions in response to fear or sexual excitement.
• Sebaceous glands are exocrine glands that secrete a lipid mixture.
• Arrector pili muscles pull hair follicles into a vertical position when the muscle contracts, creating "goose bumps."
• Hair follicles secrete the nonliving keratin shaft of hair.

The Skin

The Epidermis

• The skin surface is a mat of linked keratin fibers left behind when old epithelial cells die.
• Surface keratinocytes produce keratin fibers.
• Phospholipid matrix acts as the skin's main waterproofing agent.
• Desmosomes anchor epithelial cells to each other.
• Melanocytes contain the pigment melanin.
• Basal lamina

The Skin

Connection between Epidermis and Dermis

• Hemidesmosomes tie epidermal cells to fibers of the basal lamina.
• Basal lamina or basement membrane is an acellular layer between epidermis and dermis.