SC

Study of Tissues and Histology

5.1 The primary tissue classes

  • Tissues are groups of similar cells and cell products that arise from the same region of the embryo and work together to perform a specific structural or physiological role in an organ.
  • The four primary tissue classes: epithelial, connective, nervous, and muscular.
  • Key distinctions among tissue classes:
    • Cell types and functions vary.
    • Matrix (extracellular material) varies in composition and amount.
    • In many tissues (especially muscle and epithelium), Cells are tightly packed with little visible matrix; in connective tissue, the matrix occupies much more space than the cells.
  • Ground substance and extracellular matrix (ECM): a clear gel to rubbery medium that contains water, gases, minerals, nutrients, wastes, hormones, etc. It surrounds cells and forms the medium through which tissues obtain nutrients and dispose wastes.
  • In cartilage and bone, the ECM is more rubbery or stony rather than gel-like.
  • Summary: a tissue is composed of cells and matrix; the matrix is composed of fibers and ground substance.

5.1 B Embryonic tissues

  • Human development starts from a fertilized egg that divides to produce many identical cells.
  • Tissues first appear as cells organize into layers: the primary germ layers.
  • The three primary germ layers:
    • ectoderm (outer layer) → gives rise to epidermis and nervous system.
    • mesoderm (middle layer) → gives rise to mesenchyme and many connective tissues; later differentiates into tissues like cardiac muscle, bone, blood.
    • endoderm (inner layer) → mucous membranes of digestive and respiratory tracts and glands, among others.
  • Mesoderm differentiates into mesenchyme, a gelatinous tissue with fine, wispy collagen fibers and branching cells embedded in ground substance; mesenchyme gives rise to cardiac muscle, bone, blood, etc.
  • Most organs derive from two or more germ layers; mature tissues persist from infancy through adulthood.
  • Histology slides and two-dimensional sections: histologists preserve tissue with a fixative (e.g., formalin), section thinly (1–2 cells thick), mount on slides, and stain to reveal details.
  • Translating 2D sections to 3D structure requires understanding planes of section: longitudinal (LSN), cross (CSN), and oblique.
  • Planes of section visuals (Fig. 5.2): A longitudinal, B cross, C oblique.
  • Planes discussion: a coiled tube (e.g., gland) may appear in pieces in a section; recognition relies on knowing it is a single organ path.
  • Smears and spreads: some tissues (e.g., blood, spinal cord) can be prepared as smears; other tissues as spreads (like areolar tissue) on slides.

Test Your Understanding (from the transcript):

  • Classify the following into the four primary tissue classes: skin surface, fat, spinal cord, most heart tissue, bone, tendons, blood, inner lining of the stomach.
  • What are tissues composed of in addition to cells? What embryonic germ layer gives rise to nervous tissue, liver, and muscle? What is the term for a thin, stained slice of tissue mounted on a microscope slide?

5.2 Epithelial Tissue

  • Epithelial tissue consists of a sheet of closely adhering cells; surfaces are exposed to the environment or to internal spaces.
  • Functions of epithelia:
    • Protection (e.g., epidermis protects from infection; gastric lining protects deeper tissues from acid and enzymes).
    • Secretion (epithelia produce mucus, sweat, enzymes, hormones, and other secretions).
    • Absorption (e.g., intestinal epithelia absorb nutrients).
    • Filtration (e.g., kidney epithelium filters blood substances).
  • Epithelium is avascular (no blood vessels between cells) and rests on a vascular connective tissue layer that nourishes it; cells closest to the connective tissue have higher mitotic rates for repair.
  • Basement membrane: anchors epithelium to connective tissue and regulates exchange with underlying tissues; binds growth factors.
  • Surface polarity:
    • Basal surface faces the basement membrane.
    • Apical surface faces the body surface or organ cavity.
    • Lateral surfaces lie between cells.
  • Epithelia are classified into two broad categories: simple (one cell layer) and stratified (two or more layers).
  • More detail: four types in each category (simple and stratified):
    • Simple: squamous, cuboidal, columnar, and pseudostratified columnar (all named by cell shape; pseudostratified appears stratified but every cell contacts the basement membrane).
    • Stratified: squamous, cuboidal, columnar, and urothelium (transitional epithelium of urinary tract).
  • Simple epithelia characteristics:
    • Simple squamous: thin, flat cells; efficient for filtration and diffusion.
    • Simple cuboidal: cube-like cells; often function in secretion and absorption.
    • Simple columnar: tall, narrow cells; often have apical microvilli and goblet cells for mucus.
    • Pseudostratified columnar: all cells touch the basement membrane but appear stratified; often with goblet cells.
  • Goblet cells: secret mucus; commonly associated with simple columnar and pseudostratified epithelia.
  • Stratified epithelia: multiple layers; deeper basal cells are typically cuboidal or columnar; surface cells vary with function.
  • Stratum squamosa: deepest cells are cuboidal to columnar; mitosis occurs at the base; surface cells become flat and desquamate (exfoliation).
  • Urothelium (transitional epithelium): special stratified epithelium of the urinary tract; umbrella cells on the surface with a thickened outer membrane and lipid rafts with uroplicans to protect against urine; folds during empty bladder and unfold when stretched.
  • Keratinized vs non-keratinized stratified squamous epithelium:
    • Keratinized: epidermis; dead keratin-filled surface cells provide dry, water-repellent barrier.
    • Non-keratinized: lining of mouth, esophagus, vagina; moist and abrasion-resistant.
  • Urothelium features: umbrella cells with a thickened outer phospholipid layer; lipid rafts and uroplicans protect against urine; membrane folds adapt with bladder volume.
  • Clinical note: Biopsies and cytology (exfoliative cytology) are used for disease diagnosis (e.g., Pap smear for cervical cancer).
  • Key Figures and tables: Simple epithelium (Fig. 5.4–5.7) and Table 5.2 illustrating the four simple epithelia; Stratified epithelia (Table 5.3; Fig. 5.8–5.11).

Test Your Understanding (from the transcript):

  • Distinguish between simple and stratified epithelia; explain why pseudostratified columnar epithelium belongs in the simple category despite its superficial appearance.
  • Distinguish stratified squamous epithelium from urothelium; describe common functions of keratinized vs non-keratinized epithelia and how structure relates to function.
  • How do esophageal and stomach epithelia differ, and how does that relate to their functions?

5.3 Connective tissue

  • Connective tissues are the most abundant and histologically variable primary tissues; they include fibrous tissue, adipose tissue, cartilage, bone, and blood.
  • General features:
    • Cells occupy less space than the extracellular matrix (ECM).
    • Vascularity varies: rich networks in loose connective tissue; avascular in cartilage.
    • Functions: binding of organs, support, protection, immune defense, movement, storage, heat production, transport.
  • Mature connective tissues fall into four broad categories: fibrous connective tissue, supportive connective tissues, and fluid connective tissue.

5.3 B Fibrous connective tissue

  • Most connective tissues contain fibers; fibers are a conspicuous component here.
  • Cellular components:
    • Fibroblasts: produce fibers and ground substance.
    • Macrophages: phagocytose pathogens and debris; activate immune response.
    • Leukocytes (white blood cells): neutrophils, eosinophils, basophils, lymphocytes, monocytes; migrate through tissues; immune roles.
    • Plasma cells: synthesize antibodies.
    • Mast cells: secrete heparin (anticoagulant) and histamine (dilate vessels).
    • Adipocytes: fat cells; can appear in clusters; adipose tissue is a tissue where adipocytes dominate.
  • Fibers:
    • Collagenous fibers (collagen): tough, flexible, resist stretching; white fibers; major component of tendons, ligaments, dermis; pervade cartilage, bone, muscle.
    • Reticular fibers: thin collagen fibers coated with glycoprotein; form a sponge-like framework in spleen and lymph nodes; part of basement membranes.
    • Elastic fibers: thinner, branched, composed of elastin and fibrillin; allow stretch and recoil (e.g., skin, lungs, arteries).
  • Ground substance: gelatinous to rubbery; three major molecular classes:
    • Glycosaminoglycans (GAGs): negatively charged; attract Na+ and water; regulate water/electrolyte balance; most common is chondroitin sulfate.
    • Proteoglycans: bottle-brush shaped; large complexes with GAGs; form a hydrated gel; slow spread of pathogens; some are bound to membranes.
    • Adhesive glycoproteins: bind matrix components to cells and guide cell migration during development.
  • Types of fibrous connective tissue: loose vs dense; connective tissue can be loose (areolar, reticular) or dense (dense regular, dense irregular); elastic tissue is a specialized form.
  • Areolar tissue: loose connective tissue with abundant ground substance, many blood vessels, flexible; surrounds vessels and nerves; foundation for epithelia.
  • Reticular tissue: mesh of reticular fibers forming framework for lymphoid organs (lymph nodes, spleen, bone marrow).
  • Dense connective tissue: dense regular (tendons/ligaments; parallel collagen bundles; slow to heal due to few blood vessels) and dense irregular (random collagen bundles; resists stresses from multiple directions; in dermis and organ capsules).
  • Elastic tissue: dense with elastic fibers; found in vocal cords, spinal ligaments, and large arteries; important for recoil and vascular elasticity; Marfan syndrome is a clinical example involving elastic fibers.
  • Adipose tissue (5.3 G): adipocytes dominate; white adipose tissue (WAT) stores triglycerides; brown adipose tissue (BAT) stores lipids as multiple globules and generates heat; BAT is prominent in infants and hibernating mammals; BAT can be up to about 6% of an infant’s weight and is concentrated in shoulders, upper back, around kidneys and heart.
  • Areolar tissue, dense irregular tissue, and adipose tissue can be difficult to distinguish in some slides; look at fiber density and spacing to differentiate.
  • Cartilage and bone are discussed separately as supportive connective tissues; see 5.3 G and 5.3 F for bone and cartilage.

5.3 F Blood

  • Blood is a fluid connective tissue; composed of plasma (ground substance) and formed elements: erythrocytes (RBCs), leukocytes (WBCs), and platelets.
  • Formed elements:
    • Erythrocytes (RBCs): transport oxygen and carbon dioxide; usually anucleate in mammals.
    • Leukocytes (WBCs): defense against infection; five major types: neutrophils, eosinophils, basophils, lymphocytes, monocytes; life cycles involve moving between blood and tissues.
    • Platelets: small cell fragments involved in clotting and release growth factors for vascular growth.
  • The blood is produced by bone marrow and lymphoid organs; it contains no true fibers unless it clots.

5.3 G Cartilage and Bone (supportive connective tissues)

  • Cartilage:
    • Relative stiffness with a rubbery matrix; chondroblasts produce matrix and become chondrocytes in lacunae; cartilage is avascular—nutrition depends on diffusion.
    • Matrix rich in glycosaminoglycans and collagen; three main types:
    • Hyaline cartilage
    • Elastic cartilage
    • Fibrocartilage
    • Perichondrium surrounds most cartilage (except fibrocartilage and some hyaline). A reserve chondroblastic population persists between perichondrium and cartilage for growth.
  • Bone (osseous tissue): a hard, calcified connective tissue comprising the skeleton; two forms: compact bone and spongy bone; bone is composed of osseous tissue plus cartilage, bone marrow, and other tissues.
    • Compact bone is organized into osteons (concentric lamellae around a central canal) with lacunae housing osteocytes connected by canaliculi.
    • The bone is covered by periosteum.
    • Two-thirds of bone weight are minerals (calcium and phosphate) providing compressive strength; one-third is collagen and glycosaminoglycans providing some flexibility.

5.4 Nervous and muscular Tissues (Excitable Tissues)

  • Excitable tissues are distinguished by their ability to respond rapidly to stimuli via changes in membrane potential.
  • Nervous tissue:
    • Composed of neurons and glial (neuroglial) cells; neurons detect stimuli, respond, and transmit signals; glial cells support and protect neurons.
    • Typical neuron structure: cell body (soma), dendrites (receive stimuli), and a long axon (sends signals).
    • Glia vastly outnumber neurons and provide protective, supportive, and housekeeping functions.
    • Nervous tissue is found in the brain, spinal cord, and ganglia.
  • Muscular tissue:
    • Specialized to contract and generate force.
    • Three types of muscle tissue: skeletal, cardiac, and smooth.
    • Skeletal muscle: attached to bones; striated and voluntary; multinucleated fibers (30–77 nuclei per mm of fiber); long, cylindrical cells.
    • Cardiac muscle: found in the heart; striated but shorter, branched cells; typically one nucleus; interconnected by intercalated discs with gap junctions for synchronized contraction.
    • Smooth muscle: lacks striations; involuntary; fusiform cells with a single central nucleus; located in walls of hollow organs and vascular walls; contraction propels contents and modulates flow.

5.5 Cellular Junctions, Glands, and Membranes

5.5 A Cellular Junctions

  • Cells require junctions to grow, divide, and withstand mechanical stress; junctions regulate movement of substances between cells.
  • Types of junctions:
    • Tight junctions: encircle the cell near the apical surface; membranes are tightly bound by adhesion proteins to seal intercellular space; prevent leakage and protect tissues (e.g., stomach and intestines).
    • Desmosomes: patch-like adhesions that resist mechanical stress; anchor cytoskeletons to the membrane and create a strong network; common in epidermis, cervix epithelium, and cardiac muscle.
    • Hemidesmosomes: anchor epithelial cells to the basement membrane (half-desmosomes) preventing peeling away.
    • Gap (communicating) junctions: form a channel between cells via a ring of six transmembrane proteins; allow ions and small solutes to pass; critical for electrical coupling in cardiac and smooth muscle; absent in skeletal muscle and in lens/cornea.
  • These junctions show how structure relates to function in tissue integrity and signaling.

5.5 B Glands

  • Gland: a cellular organ that secretes substances for use elsewhere (secretion) or elimination as waste (excretion).
  • Glands are primarily epithelial tissue with supportive connective tissue and a capsule.
  • Endocrine vs Exocrine glands:
    • Endocrine glands lose contact with surface and secrete hormones directly into the bloodstream (e.g., pituitary, thyroid, adrenal).
    • Exocrine glands maintain contact with surface via ducts and secrete onto surfaces or into body cavities (e.g., salivary glands, pancreas, liver; also unicellular goblet cells).
  • Multicellular exocrine glands are enclosed by a capsule and divided into lobes by septa; parenchyma performs secretion; stroma provides support with connective tissue framework.
  • Gland architecture:
    • Simple vs compound (duct branching)
    • Tubular vs acinar (alveolar)
    • Tubulocystic or tubuloacinar (mixed ducts and secretory portions)
  • Secretory modes:
    • Merocrine (eccrine): secretion by exocytosis; examples include tear glands, salivary glands, pancreas.
    • Apocrine: apical portion of cell buds off with secretory material (lipid-rich secretions; e.g., previously thought in sweat glands, but many are actually merocrine).
    • Holocrine: entire cell disintegrates to release its product (e.g., sebaceous glands).
  • Secretions can be serous (watery) or mucous (mucin-rich), or a mixture; goblet cells are unicellular mucous glands.
  • Mucous membranes (mucosa) and serous membranes (serosa) are membranes formed by epithelia and connective tissues:
    • Mucous membranes line passages open to exterior and include mucosa-associated lymphoid tissue; composed of epithelium, lamina propria (areolar connective tissue), and sometimes muscularis mucosae.
    • Serous membranes line body cavities and cover viscera; consist of simple squamous epithelium (mesothelium) resting on areolar tissue; secrete watery serous fluid.
    • Endothelium lines circulatory system; derived from mesoderm; forms tunica interna of vessels and endocardium of the heart.

5.6 5.6 Tissue growth, development, repair, and degeneration

5.6 A Tissue growth

  • Tissues grow by two mechanisms:
    • Hyperplasia: increase in cell number
    • Hypertrophy: increase in cell size (e.g., skeletal muscle and adipose tissue growth via hypertrophy rather than increased cell numbers)
  • Neoplasia: development of a tumor (neoplasm) that is abnormal, nonfunctional tissue.
  • Postnatal growth is largely via hyperplasia and hypertrophy depending on tissue type.

5.6 B Tissue development

  • Tissues can change from one type to another (differentiation) and sometimes undergo metaplasia.
  • Example: vaginal epithelium changing from simple cuboidal to stratified squamous epithelium during puberty to accommodate functional demands; long bones change from red to yellow bone marrow with age; bronchial pseudostratified columnar epithelium can undergo metaplasia to stratified squamous epithelium in smokers.
  • Function and structure relate to environmental demands; metaplasia can alter tissue function and susceptibility to disease.

5.6 C Stem cells

  • Growth and differentiation depend on stem cells: undifferentiated cells with potential to differentiate into multiple mature cell types.
  • Two main types:
    • Embryonic stem cells (ESCs): totipotent/pluripotent; early embryo (inner cell mass) can form any cell type, including placenta; developmental plasticity is extensive; sources include surplus IVF embryos; ethical concerns exist.
    • Adult stem cells: reside in mature tissues; more limited plasticity; generally multipotent, capable of forming a few lineages; examples include hematopoietic stem cells in bone marrow that produce blood cells.
  • Induced pluripotent stem cells (iPSCs): adult cells reprogrammed to a pluripotent state, offering potential for patient-specific therapies but with technical and safety challenges.
  • Clinical context: stem cell therapies show promise (bone marrow transplants, cord blood), but broad clinical adoption requires overcoming safety, efficacy, and ethical concerns. Organ regeneration and tissue engineering are under active research (e.g., decellularized scaffolds reseeded with patient cells; organ-on-a-chip technology).
  • Deeper insights: regulatory, ethical, and practical considerations around stem cell therapies, regulatory status, and ongoing clinical trials collaborate with regenerative medicine.

5.6 D Tissue Repair

  • Damaged tissues repair via two main processes:
    • Regeneration: replacement of dead/ damaged cells with the same type of cells, restoring normal function.
    • Fibrosis: replacement with scar tissue (collagen) produced by fibroblasts; restores structural integrity but not full function.
  • Wound healing sequence (skin injury example):
    1) Severed vessels bleed; histamine release increases permeability and blood flow.
    2) Blood clot forms to seal wound and prevent infection.
    3) Clot dries to form a scab; macrophages remove debris.
    4) Granulation tissue forms with new capillaries and fibroblasts; epithelial cells migrate beneath the scab.
    5) Epithelial layer thickens; underlying connective tissue undergoes fibrosis.
    6) Remodeling/maturation can last weeks to two years; scar may become less noticeable.
  • Regenerative medicine: tissue engineering and regenerative approaches aim to restore function by creating functional tissues or organs; decellularized scaffolds reseeded with patient cells; organ-on-a-chip models for drug testing; potential future therapies include engineered vessels, heart valves, patches of cardiac muscle, etc.
  • Practical cautions: stem cell therapies can be dangerous if unregulated; patient safety and regulatory oversight are critical.

5.6 E Tissue degeneration and death

  • Atrophy: shrinkage of tissue through loss of cells or cell size; due to aging or disuse; examples include muscle atrophy in spaceflight or immobilization.
  • Necrosis: pathological tissue death due to trauma, toxins, or infection; often triggers inflammation.
    • Infarction: sudden tissue death due to loss of blood supply (e.g., myocardial infarction, cerebral infarction).
    • Gangrene: necrosis due to infection or severely impaired blood supply; dry vs wet gangrene; dry is common in diabetes and involves dry, shrunken tissue; wet gangrene involves infection and liquefaction.
  • Decubitus ulcers (pressure ulcers): bedsore due to prolonged pressure, commonly in immobile patients.
  • Apoptosis: programmed cell death; normal in development and homeostasis; cells shrink and are rapidly phagocytosed; no inflammatory response because contents are not released.
  • Deeper insights (clinical): regenerative medicine and stem cells are not yet a universal solution; iPSCs show potential but come with risks (tumor formation, misplacement); clinical trials and FDA oversight are critical.

Deeper Insights and Clinical Connections (throughout 5.6)

  • Regenerative medicine and organ engineering: decellularization and recellularization strategies; organ-on-a-chip as models for drug testing and personalized medicine; tissue engineering successes include engineered skin, cartilage repair, bladder tissue, and vascular grafts.
  • Practical considerations: ethical issues surrounding ESCs; advances led to iPSC technology but challenges remain in safety, efficacy, cost, and regulatory approval.
  • Clinical trends: ongoing global stem cell trials; common targets include neurodegenerative diseases, diabetes, macular degeneration, spinal cord injuries, and dental/craniofacial applications; FDA continues to regulate and assess safety of stem cell therapies.

Practice and Reflection (Key Questions)

  • What are the three basic modes of tissue repair, and which one restores function? What is the role of fibrosis if function is not fully restored?
  • How do hyperplasia and hypertrophy differ, and in which tissues are each typically observed?
  • What is metaplasia, and can you give an example from the transcript?
  • Distinguish between simple and stratified epithelia, and explain why pseudostratified columnar epithelium is considered simple.
  • Compare connective tissue types by their primary components: cells, fibers, and ground substance; how does this relate to their function?
  • Name the three main cartilage types and note a distinctive feature of perichondrium.
  • Describe the basic plan of bone structure: osteon, central canal, lacunae, canaliculi, and periosteum.
  • What are the three kinds of muscular tissue, and how do you identify them in histology and on the basis of function?
  • Differentiate endocrine and exocrine glands by their ducts and target tissues; give an example of each.
  • What are the major components of a mucous membrane, and what are its typical functions? How does a serous membrane differ?
  • Explain the planes of section (longitudinal, cross, oblique) and why this matters for interpreting histology slides.

ext{Growth types:} egin{aligned} ext{Hyperplasia} &: ext{ increase in cell number} \ ext{Hypertrophy} &: ext{ increase in cell size} \ ext{Regeneration} &: ext{ replacement with the same cell type} \ ext{Fibrosis} &: ext{ replacement with scar tissue} \ ext{Differentiation} &: ext{ maturation from stem cell to specific cell type} \ ext{Metaplasia} &: ext{ one mature tissue type changing to another} \ ext{Apoptosis} &: ext{ programmed cell death with minimal inflammation} \ ext{Necrosis} &: ext{ pathological cell death with inflammation} \ ext{Infarction} &: ext{ tissue death due to ischemia} \ ext{Gangrene} &: ext{ necrosis with infection or severe ischemia} \ ext{Totipotent} &: ext{ potential to form any cell including placenta} [6pt] ext{Pluripotent/Multipotent} &: ext{ limited lineage options} \ ext{iPSC} &: ext{ induced pluripotent stem cells (reprogrammed somatic cells)} \ ext{ESC} &: ext{ embryonic stem cells (totipotent/pluripotent in early stages)} \ ext{Tissue engineering} &: ext{ decellularized scaffolds seeded with patient cells} \ ext{Organ-on-a-chip} &: ext{ microfluidic devices that mimic organ-level physiology} \ ext{Clinical trial landscape} &: ext{ thousands of trials; regulatory oversight essential} \ ext{Regeneration vs. repair} &: ext{ regeneration restores function; fibrosis supports structure} \ ext{Regenerative medicine outlook} &: ext{ promising but gradual translation to clinics} \
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