Specialized extracellular matrix which anchors cells to underlying connective tissue
Synthesized by epithelia
Has two layers
Layers of basal lamina
Lamina densa, which contains fine fibrils
Lamina lucida, which is the electron lucent layer next to the basal cell surface and the lamina densa
Functions of basal lamina
Structure and organization (attachment of epithelium to connective tissue and organization of the basal membrane)
Filtering (acts as a barrier regulating exchange between epithelium and connective tissue)
Regulation (binds growth factors that regulat cell proliferation, differentiation, and metabolism)
Migration (orients movement of epithelial cells)
Main components of basal lamina (4)
Type IV Collagen
Laminins
Entactin (nidogen)
Perlecan
What is the name of an autoimmune disease in which the patient has damage to basal laminae and epithelial cells?
Goodpasture's syndrome, in which patients synthesize antibodies that bind to type IV collagen, resulting in progressive renal failure and pulmonary hemorrhage
Epithelial cell shapes can be easily determined by examining the:
Cell nucleus, which parallels the shape of the cell
Blood vessels penetrate the epithelium (T/F)?
False. They penetrate the supportive, underlying connective tissue
Lamina propria
The connective tissue which lies beneath epithelial cells and the basal lamina. Blood vessels penetrate this tissue.
Type IV collagen
Trimeric molecules with rodlike and globular domains that form a 2D network, making up most of the basal lamina
Laminins
Multiadhesive proteins that form a fibrous 2D network with type IV collagen, providing attachment sites for epithelial cells
Entactin (nidogen)
A rodlike molecule that crosslinks type IV collagen and laminin and helps incorporate other components into the basal lamina
Perlecan
A large, multidomain heparan sulfate proteoglycan that binds to and crosslinks many components of the basal lamina and cell surface proteins
Basement membrane
Two basal laminae attached to one another as seen in the kidney glomeruli or
The basal lamina of the epithelial cells attached to the reticular lamina of connective tissue cells
It is not synonymous with basal lamina, as it is thicker
Anchoring fibrils
Type VII collagen fibrils embedded in a heparan sulfate gel that anchor the basal lamina to the underlying connective tissue
What type of junction anchors the basal membrane of epithelial cells to the basal lamina?
Hemidesmosomes
What are the transmembrane receptors involved in hemidesmosomes?
Integrins, such as alpha-6-beta-4
They link the basal lamina outside the cell to the keratin-based intermediate filament cytoskeleton inside the cell
Types of adhering junctions (2)
Zonulae adherens
Desmosomes
Types of impermeable junctions (1)
Zonulae occludentes (aka tight junctions)
Types of communicating junctions (1)
Gap junctions (aka intercytoplasmic junctions)
Zonula versus macula
Zonula means belt-like and macula means spot-like
Zonulae occludentes
Aka tight junctions
Found at the most apical portion of the lateral surface of epithelial cells
Prevents macromolecules and some water/ions from diffusing across sheets of epithelial cells
Cholera
Caused by vibrio cholerae (and other enteric bacteria)
Toxins produced by these bacteria alter the tight junction permeability barrier of intestinal epithelia by changing the composition or activity of tight junctions
Massive loss of ions and water into the GI tract occurs, leading to diarrhea and potentially lethal dehydration
Zonulae adherens
Aka adherens junctions
Located near the apical surface, just below tight junctions
Associated with actin/myosin belt that functions as a tension cable to control cell shape
Actin filaments arise from a terminal web, a meshwork of actin, intermediate filaments and spectin in the apical region of the cell
Provides the primary adhesive junctions between adjacent cells in an epithelium by linking actin filaments between adjacent cells
Uses cell adhesion molecules (CAMs) and cadherins (E-cadherins)
Maculae adherens
Aka desmosomes
Button-like points of attachment between adjacent epithelial cells via attachment plaques
Attach internal to the cell via tonofilaments, which are intermediate filaments composed of cytokeratins that insert into attachment plaques or make hairpin turns and return to the cytoplasm
Provide tight adhesion between adjacent epithelial cells by linking tonofilaments from cell to cell
Pemphigus vulgaris
An autoimmune disorger in which patients synthesize antibodies that bind to desmosomal cadherins and disrupt desmosomes and cell-cell adhesion
Results in blistering skin
Intercytoplasmic junctions
Aka gap junctions
Present in epithelia but also abundant in nearly all tissues except for skeletal muscle
Allows communication between cells by permitting passage of small molecules and ions
Made up of connexons, which are hydrophilic channels made up of connexin proteins
Microvilli
Fx: Increase cell surface area for absorption
Actin microbilaments are in the center of each microvillus and are anchored in the terminal web
The outer surface has a thick coat of glycoproteins, called the glycocalyx (appears as a "brush or striated border")
Stereocilia
Fx: Increase cell surface area for absorption (as in the epididymis) or sense fluid motion or fluid pressure (as in the inner ear hair cells)
Like long, branched microvilli
Cilia and Flagella
Fx: Movement (flagella) and removal of foreign particles, bacteria and mucus from the lungs or exterior of nose (cilia)
Made of microtubules in a 9 + 2 arrangement that insert into basal bodies
Basal bodies
Electron-dense structures at the apical pole of epithelial cells
Allow for attachment of microtubules
Structurally analogous to centrioles
Non-motile primary cilia
Elongated structures that do not move on their own but can bend upon external pressures (such as fluid flow)
Nearly all differentiated cells of adult tissues, including most epithelial cells, fibroblasts, chondrocytes, osteocytes, smooth muscle cells, skeletal and cardiac muscle, photoreceptor cells, hippocampal neurons, etc. have a primary cilium
Made of microtubules in a 9 + 0 arrangement and insert into basal bodies
Polycistic Kidney Disease and non-motile primary cilia
Polycystis are disrupted in polycystic kidney disease and result in inability to sense fluid flow
These polycystins form a fluid-sensing mechanism that control the diameter of renal tubules
Types of covering epithelia based upon layers (3)
Simple
Stratified
Pseudostratified (all cells contact the basal lamina, but not all cells reach the free surface)
Types of covering epithelia based upon shape (3)
Squamous
Cuboidal
Columnar
(These classifications are determined by the most superficial layer)
Simple squamous epithelium (distribution and function)
Distribution: Inner surface of tympanic membrane, part of nephrons (Bowman's capsule and loop of Henle), lungs, testes, the smallest excretory ducts of many glands, mesothelium lining serous cavities, mesenchymal epithelium lining cavities in connective tissue, and endothelium lining the walls of blood and lymph vessels
Fx: Exchange, barrier, lubrication
Simple cuboidal epithelium (distribution and function)
Distribution: Small ducts of exocrine glands, choroid plexus (in ventricles of brain which secrete or absorb CSF), free surface of the ovary, thyroid follicles, inner surface of the lens capsule, retinal pigment epithelium, and kidney tubules
Simple columnar epithelium (distribution and function)
Distribution: Digestive tract, excretory ducts of glands, gallbladder
Ciliated simple columnar epithelium: Uterus and oviducts, small bronchi of the lung, paranasal sinuses, central canal of spinal cord
Fx: Absorption and secretion
Side note--often found with goblet cells, which secrete fluids and are unciliated
Stratified squamous epithelium (types, distribution, and function)
Non-keratinized stratified squamous epithelium: Moist surfaces, lining wet cavities (mouth, vagina, female urethra, anus, esophagus, part of epiglottis, part of conjuctiva adn conrea in the eye)
Keratinized stratified squamous epithelium: Skin and hard palate
Fx: Barrier, protection
Stratified cuboidal epithelium (distribution and function)
Stratified columnar epithelium (distribution and function)
Relatively rare
Distribution: Fornix of conjunctiva, cavernous part of urethra, anal mucous membrane, pharynx, epiglottis, large excretory ducts of some glands
Ciliated stratified columnar epithelium: Nasal surface of the soft palate, larynx, fetal esophagus
Fx: Barrier, conduit
Pseudostratified columnar epithelium (distribution and function)
Distribution: Large excretory ducts of the parotid and other glands, male urethra
Ciliated pseudostratified columnar epithelium: Greater part of mucous membrane of respiratory passages (trachea, bronchi, nasal cavity), pharyngoauditory tube, part of typmanic cavity, lacrimal sac, and excretory passages of the male reproductive system
Fx: Secretion, absorption, conduit
Transitional epithelium (definition, distribution, and function)
Definition: Epithelial cells that vary in appearance because they are subject to great mechanical changes due to contraction and distention
Distribution: Urinary bladder, ureters, and upper part of urethra
Fx: Barrier, distensible property
Metaplasia
A reversible event where one differentiated cell type is replaced with another mature differentiated cell type
Usually an adaptation to cellular stress (NOT cancer)
Examples: Barrett's esophagus, airway epithelial metaplasia (replacement of ciliated pseudostratified columnar cells with stratified squamous cells in response to cigarette smoke), and cervical erosion (non-keratinized stratified squamous epithelium is replaced by glandular columnar epithelium, caused by trauma, infections, and chemicals)
Size classifications of glandular epithelium (2)
Unicellular (only goblet cells)
Multicellular
Goblet cells
Unicellular glands (aka mucous cell) that secrete mucin, a protein-polysaccharide that forms a lubricating solution
Mode of secretion classifications of glandular epithelium
Exocrine glands: Secrete into ductal system, retain connections with surface epithelium from which they were derived, discharge product at an external or internal surface
Endocrine glands: Secrete into vascular system, do not retain connections with surface epithelium of origin, do not have ducts
Secretory product classifications of glandular epithelium (3) and examples
Serous: Parotid gland and pancreas
Mucous: Goblet cells and mucous salivary gland
Mixed: Submandibular and sublingual salivary glands
Alveoli
Spherical structures that adjacent serous cells form within serous glands
Zymogen granules
Contain digestive enzymes and are found in serous cells; separate from secretory granules
Mechanism of secretion classifications of glandular epithelium (3)
Merocrine
Apocrine
Holocrine
Merocrine
Secretory granule fuses with plasma membrane by exocytosis without accompanying loss of cytoplasm
Salivary glands and pancreas
Apocrine
Secretory granule plus apical cytoplasm is lost
Mammary glands and sweat glands
Holocrine
Entire cell becomes secretory product and is shed
Uncommon
Sebaceous gland (cells that produce sebum which are found on skin and near hair follicles)
Glandular morphology classifications of glandular epithelium
Densely-packed thick fibers and bundles with variable diameters
Most abundant form, found in dense and loose CT, skin, tendons, fibrous cartilage, organ capsules, bones, cornea, dentin
Made by fibroblasts and specialized CT cells such as osteoblasts, odontoblasts, and chondroblasts
Type II collagen
Fx: Resistance to intermittent pressure
Usually found with many fibril-associated proteins and lots of ground substance, giving it a shock-absorbing property
Does not form thick fibers--only very thin fibrils
Found in hyaline and elastic carilages and vitreous body (intervertebral discs)
Made by chondroblasts
Type III collagen
Fx: Structural maintenance in expansible organs
Forms reticular fibers, which are loosely-packed thin fibrils with uniform diameters
Found in smooth muscle, arteries, uterus and in networkds around cells in spleen, lymph nodes, bone marrow, liver, kidney, and endocrine glands
Made by fibroblasts, smooth muscle cells, reticular cells, Schwann cells, and hepatocytes
Visual differences of types I, II, and III collagens
Type I: Strongly birefringent (transmits light unequally in different directions) yellow or red fibers, nonargyrophilic (not capable of binding silver salts)
Type II: Visible only with picro-Sirius stain and polarization microscopy
Type III: Weakly birefringent greenish fibers, argyrophilic (does bind silver salts because more sugars are associated with these loosely-packed reticular fibers)
Under EM: Fibrils have a striabed appearance due to lacunae and overlapping regions
Type VII collagen
Anchors skin epidermal basal lamina to connective tissue
Ehlers-Danlos type IV disease
Deficiency of type III collagen (reticular fibers) characterized by ruptures in arteries (often aorta) and intestines
Ehlers-Danlos type VI disease
Defects in processing type I collagen and causes hyperextensible skin but increases chance of eyeball rupture
Ehlers-Danlos type VII
Patients have double-jointedness
Synthesis of collagen
Pro-a-chains are made first
Procollagen is assembled in the ER
Proline and lysine residues are hydroxylated in the ER
Procollagen is packaged into secretory vesicles in the Golgi and secreted
Procollagen peptidases cleave procollagen into insoluble tropocollagen, which polymerizes in an overlapping pattern to form collagen fibrils
Scruvy
Caused by a deficiency of vitamin C, which is a cofactor for the hydroxylation of proline and lysine residues
Bone growth, wound and fracture healing, and stability of adult organs may be affected, in addition to periodontal bleeding and ulceration
Elastic fibers
Found in almost all connective tissue, but is enriched in places that must stretch and relax (skin, tendons, heart, blood vessels, fascia of anterior abdominal wall)
Made by fibroblasts and smooth muscle cells
Components of elastic fibers (2)
Microfibrils: Elastic scaffold consisting of fibrillin and associated glycoproteins
Elastin: A non-glycosylated protein that forms amorphous deposits
Development of elastic fibers
1) Oxytalan fibers: Lattice of fibrillin without elastin
2) Elaunin fibers: Elastin protein is deposited and surrounds oxytalan fibers
3) Elastic fibers: Blob of elastin surrounded by tubular microfibrils
Marfan syndrome
Mutations in the fibrillin gene result in defective elastic fibers
Tissues rich in elastic fibers (such as large arteries) suffer a lack of resistance and patients often suffer ruptures in the aorta
Ground substance main components (2)
Glycosaminoglycans (GAGs) and glycoproteins
Glycosaminoglycans
Linear (non-branching) polysaccharides
All GAGs are in proteoglycans except for hyaluronic acid
Proteoglycan
Made up of glycosaminoglycans and a protein core
Dermatan sulfate
A GAG associated with type I collagen; found in the dermis, tendons, ligaments, and fibrocartilage
Chondroitin sulfate
A GAG associated with type II collagen; found in hyaline and elastic cartilage
Heparan sulfate
A GAG associated with types III and IV collagens; found in reticular fibers and basal laminae
Keratan sulfate
A GAG found in cartilage
Functions of glycosaminoglycans
Structural: Bind together protein fibers of ECM and anchor cells to ECM
Hydration: Bind lots of cations (usually sodium) and water
Glycoproteins
Protein-sugar macromolecules composed primarily of proteins (whereas proteoglycans are primarily carbohydrate)
Examples: Fibronectin (cell adhesion and migration), chondronectin (holds chondrocytes to collagen), and laminin (binds epithelia to basal lamina)
Indigenous connective tissue cells
Are generated in the connective tissue and produce the ground substance of the tissue
Includes primitive mesenchymal cells, fibroblasts and fibrocytes, and adipose cells
Immigrant connective tissue cells
Cells that migrate into connective tissue. Their main functions are immunological and defense (phagocytosis, cytokine production, antigen presentation, and allergic reactions)
Includes mast cells, neutrophils, monocytes, macrophages, lymphocytes, plasma cells, and eosinophils.
Primitive mesenchymal cell (origin and function)
Arise from embryonic mesenchyme (mesoderm) which is plentiful in the fetus. These multipotent undifferentiated CT cells then decrease in numbers until persisting as single cells along small blood vessels in the adult.
Fx: Produce more indigenous CT cells
Fibroblast (origin and function)
Arise from primitive mesenchymal cells
Fx: Make and secrete the fibers and ground substance of CT ECM (collagen, elastin, GAGs and PGs, and adhesive glycoproteins)
Also play a role in wound healing by repairing the area by making protein fibers and ground substance
Adipose cell (origin and function)
Arise from primitive mesenchymal cell
Fx: Store neutral triglycerides. These triglycerides remain in the cell for an average of 4 days. "Brown" fat cells (multilocular cells) are important for heat production in babies and hibernating animals. Human adults have only unilocular tissue cells.
Hypertrophic obesity
Excessive fat accumulation in unilocular tissue cells that become abnormally large
Hyperplastic obesity
Excessive fat accumulation in which adipocyte number increases
Mast cell (origin and function)
Arise from hematopoietic stem cells in the bone marrow
Fx: Begin the inflammatory response, which is important for beginning allergic reactions. Also recruits eosinophils. Secretes granules containing heparin (anti-coagulant), histamine (increases permeability of vascular endothelial cells), and proteolytic enzymes, which can cause itching and edema.
Polymorphonuclear leukocyte (origin and function)
Aka neutrophils
Arise from bone marrow and respond to chemotactic factors to migrate via bloodstream
Fx: Rapid defense system, phagocytosis following recognition by complement or IgG. Cells are committed to die after phagocytosis because they are unable to synthesize more granules (lysosomes) or membrane receptors.
Monocyte (origin and function)
Arise from bone marrow and respond to chemotactic factors to migrate via bloodstream
Fx: Provide a population of potential macrophages to CT
Macrophage (origin and function)
Arise from monocytes
Fx: Defend the body by ingesting and killing bacteria and fungi which have been coated by IgG or serum complement, ingest wastes such as dead cells and foreign particles, and store wastes in residual bodies
In addition, they can further mature to give rise to specialized macrophages for specific tissues, such as osteoclasts (bone), Langerhans cells (skin), and dendritic cells (lymph nodes)
Lymphocyte (origin and function)
Arise from bone marrow or lymphatic nodules in CT. They are motile and migrate through endothelia and epithelia.
Fx: Immunologic (T cells initiate cell-mediated immune response and B cells divide and produce plasma cells). Both have receptor sites for antigens on the surface membrane
Plasma cell (origin and function)
Arise from B lymphocytes in CT
Fx: Synthesize and secrete large amounts of a specific immunoglobulin (up to 2000 mol/sec)
Eosinophil (origin and function)
Arise from bone marrow via bloodstream
Fx: Participate in response to allergies and certain parasitic infections
Types of connective tissue proper
Loose
Dense irregular
Dense regular
Loose (areolar) ordinary CT
Many cells and ground substance
Made up of an irregular arrangement of collagen fibrils and elastic fibers
Fx: Flexibility
Found in mesentary, next to epithelium, and around blood vessels and glands
Dense irregular CT
Few cells and ground substance
Made up of a non-parallel, rough-lattice arrangement of collagen fibers and a random arrangement of elastic fibers
Fx: Resist stress
Found in dermis, organ capsules, periosteum, and perichondrium
Dense regular CT
Few cells and ground substance
Made up of a parallel arrangement of collagen fibers and varying amounts of elastic fibers
Fx: Resist stress
Found in tendons and ligamens, and in the cornea of the eye (GAG matrix and no elastin)
Types of cartilage
Hyaline, elastic, fibrous
Hyaline cartilage
Made up of many type II collagen fibrils in a homogenous mixture
Fx: Cusion forces, form temporary skeleton
Found in articulations, the temporary skeleton, ventral ends of ribs, larynx, trachea, and bronchi
Elastic cartilage
Made up of many type II collagen fibrils and numerous branched elastic fibers
Many chonbroblasts
Fx: Flexible skeleton
Found in the auricle of the ear, the external auditory meatus, the auditory tube, epiglottis, and parts of the larynx
Fibrous cartilage
Made up of type I collagen fibers (resembling dense connective tissue), resulting in a little matrix that is acidophilic (collagen has many + charges)
Few cells and proteoglycans
Fx: Stability
Found in tendon attachments and linings, intervertebral discs, and the pubic symphysis
Cartilage ECM
Made of collagen, proteoglycan aggregates (GAGs that are hydrated gels attached to proteins), and glycoproteins (adhesive proteins that bind cells and ECM such as integrins)
Chondroblasts
Free, untrapped cells in the ECM of cartilage that secrete matrix and fibers
These cells persist int he perichondrium and undergo mitosis
Chondrocytes
Cells that are trapped in lacunae of cartilage and are surrounded by matrix
They bind to the collagen in the ECM via chondronectin
Have mitotic potential during growth but are limited in adult
Chondronectin
An adhesion molecule (glycoprotein) which binds chondrocytes to collagen in the ECM of cartilage
Growth of cartilage
Interstitial (inside the cartilage tissue) growth occurs only in the young and results in isogenic populations of cells in cell nests
Appositional growth is from the outside inwards from the chondrogenic layer of perichondrium
Somatomedin C and other growth factors promote cartilage synthesis
Somatomedin C
A growth factor made by the liver which stimulate cartilage production
Layers of perichondrium (2)
An outside, fibrous layer (where fibroblasts secrete type I collagen)
An inside, chondrogenic layer (where appositional growth occurs via chondroblasts)
Regeneration of cartilage
Typically does not occur due to low metabolic rate. Tissue is avascular and receives nutrients from matrix. Does occur more easily in children
Intervertebral disc composition
Annulus fibrosis: Fibrocartilage surronded by external layer of dense connective tissue
Nucleus pulposis (aka hyaline plate): Gel-like, contains hyaluronic acid and type II collagen
Key characteristics of bone versus cartilage
Dense collagen matrix
Mineralized matrix
Repairable
Remodeling
Compact (cortical) bone location
Found on the surfaces of all bones
Spongy (cancellous) bone
Found in the interior of bones. Has a honeycomb appearance, which reduces bone weight while still providing support. Marrow is found within spaces.
Osteon
A central canal and the concentric osseous lamellae encircling it, occurring in compact bone. Also called the Haversian system, it is necessary for blood, lymph, and nerve supply.
Layers of periosteum
Fibrous outer layer and osteogenic inner layer
Endosteum
The inner lining of bone surfaces made up of osteogenic cells and small amounts of collagen
Non-mitotic cells that arise from osteoprogenitor cells
Secrete bone constituents (collagen and matrix)
Osteocytes
Non-mitotic cells that are trapped in lacunae which are necessary for survival. They form cell-cell contact via gap junctions
Bone is not vascularized but does contain nerves (T/F)
False. Bone is both vascularized and does contain nerves
Canaliculi (in compact bone)
Canals between adjacent lacunae that contain osteocyte processes
Cement line (in compact bone)
A 1-2um thick matrix with adhesion molecules but no collagen
Volkmann's canals
Connect parallel Haversion canals
Patterns of lamellae (3)
Interstitial: Between osteons
Concentric: In osteons
Circumferential lamellae: At outer and inner bone surfaces
Trabeculae
Branching connections that are found in spongy bone. They must be about .2mm in order to maintain weight
Location of spongy bone
All immature bone and interiors of mature bones
Blood supply patterns to long bones
Diaphyseal: Supply to the shaft of the long bone from the nutrient artery
Epiphyseal-metaphyseal: Supply to the ends of long bones which have distinct supply to the epiphysis and metaphysis
Major components of organic bone matrix
Collagen (type I mostly), binding proteins, glycoproteins, and growth factors
Major components of inorganic bone matrix
Hydroxyapatite needles, amorphous CaPO4, and minerals, which are stored in bone
Hydroxyapatite crystals
Give bone its hardness. Are found in needle-like shapes, with an interior surface and a hydration shell, which facilitates ion exchange between the crystals and body fluids
Osteoclasts
Multinucleated cells derived from the fusion of multiple monocytes which cause bone resorption at the ruffled border
Bone resorption mechanism
Oteoclasts release hydrolytic enzymes from lysosoes to remove organic matter and H+ to dissolve minerals and activate the enzymes by creating an acidic environment
Osteopetrosis
Dense bone caused by a genetic disease. Osteoclasts do not have ruffled borders and cannot resorb enough bone
Wolff's law
Use and disuse of bone are directly related to their internal architecture by opposite effects (ex: bed rest leads to bone loss and activity leads to bone deposition)
Osteoporosis
Decreased bone density caused by an imbalance of bone resorption and deposition (age related, diet deficiencies, endocrine, drug related)
Major sites: Vertebrae, femoral necks, and wrists
Hormones which cause increased bone matrix
Calcitonin: Inhibits osteoclast resorption
Estrogens: Decrease rate of bone turnover
Androgens: Increase bone density
Growth hormone: Increases bone deposition
Hormones which cause decreased bone matrix
Parathyroid hormone: Cause a calcium shift from the matrix to extracellular fluid (hypercalcemia)
Thyroxine: Stimulates osteoclast resorption
Epiphyseal disk
Aka growth plate
The plate of cartilage which separates diaphyseal and epiphyseal bone during growth
Has zones of inactivity, proliferation, hypertrophy, and calcification
Metaphpysis
A region of bone on the diaphyseal side of the epiphyseal disk which is characterized by ossification at the edge of the cartilage and by resorption of bone on its interior surfaces towards the diaphysis
Immature bone
Has more cells than mature bone
Is non-lamellar, has more heterogeneous ECM, and collagen is disorganized
Mature bone
Lamellar bone in which collagen is oriented in the same plane (but is perpendicular in the next lamella)
Diaphysis
Aka the shaft, the primary center of ossification in a long bone