Chapter 06 - Integumentary System Flashcards

Cellular Metabolism

Metabolic Reactions: Anabolism and Catabolism

• Cellular metabolism refers to the collective sum of all chemical reactions occurring within a cell, organized primarily into interconnected pathways or metabolic cycles.

• Metabolism consists of two fundamental components:

  • Anabolism: Synthetic pathways in which smaller, simpler molecules are constructed into larger, complex structures. These reactions require energy input, typically supplied by ATP generated during catabolic reactions.

  • Catabolism: Degradative pathways in which larger molecules are broken down into smaller, simpler constituents. These reactions release energy.

Anabolism and Dehydration Synthesis

• Anabolic processes produce necessary cellular materials required for maintenance, cellular growth, and tissue repair.

• Dehydration Synthesis: A primary anabolic mechanism used to join small molecular units together:

  • In dehydration synthesis, a hydrogen atom ($\text{H}$) is removed from one subunit and a hydroxyl group ($\text{OH}$) is removed from another, joining the subunits and releasing a molecule of water ($\text{H}_2\text{O}$).

  • Carbohydrates: Monosaccharides (e.g., glucose) undergo dehydration synthesis to form disaccharides (e.g., maltose) and polysaccharides (e.g., glycogen).

  • Lipids: Three fatty acid molecules combine with one glycerol molecule via dehydration synthesis to yield one triglyceride molecule and three water molecules ($3\,\text{H}_2\text{O}$).

  • Proteins: Amino acids combine via dehydration synthesis; an amide link called a peptide bond forms between the carboxyl group of one amino acid and the amino group of another, forming dipeptides and extended polypeptide chains.

Catabolism and Hydrolysis

• Catabolic processes decompose carbohydrates, lipids, and proteins into their foundational building blocks.

• Hydrolysis: The primary catabolic cleavage mechanism, representing the chemical reverse of dehydration synthesis:

  • A water molecule ($\text{H}_2\text{O}$) is consumed to break the covalent bond between molecular subunits, splitting water into a hydrogen atom ($\text{H}$) attached to one subunit and a hydroxyl group ($\text{OH}$) attached to the other.

  • Hydrolysis breaks down polysaccharides into monosaccharides, triglycerides into glycerol and fatty acids, and proteins into free amino acids.

Control of Metabolic Reactions and Enzymes

• Cellular survival requires precise regulation of reaction rates so that energy-releasing catabolic reactions occur at rates that strictly balance energy-utilizing anabolic reactions.

• Enzymes: Specialized globular protein catalysts that control the rates of both anabolic and catabolic reactions.

  • Enzymes accelerate reaction rates by dramatically lowering the activation energy required to initiate a reaction.

  • Enzymes are not consumed or altered during the chemical process, allowing them to be reused repeatedly.

  • Enzymes exhibit high substrate specificity based on the exact 3D spatial conformation of their active site.

  • Enzyme nomenclature typically utilizes the name of its specific substrate combined with the suffix -ase (e.g., lipase catalyzes lipid breakdown).

Enzyme Action Sequence

1. Substrate molecules encounter and fit into the active site of the enzyme molecule.

2. Temporary binding creates an enzyme-substrate complex.

3. The reaction occurs, transforming the substrate into a distinct product molecule.

4. The unaltered enzyme molecule releases the product and is immediately available to bind new substrate molecules.

Cofactors, Coenzymes, and Denaturation

• Cofactor: A non-protein component essential for enzyme activity. Cofactors help fold active sites into proper active conformations or directly assist in binding enzymes to substrates. A cofactor may be an inorganic ion, element, or small organic molecule.

• Coenzyme: An organic cofactor molecule. Most coenzymes are derived from dietary vitamins, which are essential organic nutrients that human cells cannot synthesize independently.

• Denaturation: The irreversible loss of an enzyme's functional 3D conformation, disrupting the active site so it can no longer bind substrate molecules. Denaturation can be induced by heat exposure, radiation, extreme pH values, electricity, or specific toxic chemicals.

Metabolic Pathways and Regulation

• Metabolic Pathway: A sequential series of enzyme-catalyzed reactions where the product of one enzymatic reaction serves as the substrate for the subsequent step.

• Rate-Limiting Enzyme: An enzyme that sets the pace for an entire metabolic sequence.

  • The rate-limiting step is typically catalyzed by the first enzyme in a metabolic sequence, present in strictly limited concentrations.

  • In many pathways, the final product acts through negative feedback to inhibit the rate-limiting enzyme, preventing overproduction of the end product.

Metabolic Applications and Diseases

• Human Metabolome: The complete set of small molecules and metabolites participating in cellular metabolism within a cell, tissue, organ, or organism. The Human Metabolome Database catalogues these compounds (estimating over 2,500 distinct human cellular metabolites) to analyze concentrations, drug/food interactions, and pathway interfaces for clinical toxicology and diagnostic screening.

• Inborn Errors of Metabolism: Inherited genetic mutations resulting in deficient or absent metabolic enzymes.

  • Lacking a functional enzyme blocks the catalyzed pathway, causing substrate accumulation behind the block and product deficiency downstream.

  • Phenylketonuria (PKU): An inherited metabolic disorder where a missing enzyme blocks the normal conversion of the amino acid phenylalanine into tyrosine. Accumulating excess phenylalanine enters the bloodstream and damages brain tissue. PKU is managed clinically through specialized dietary restriction.

Cellular Respiration and Energy Production

• Energy: The biological capacity to change matter or perform cellular work. It exists in forms including heat, light, sound, electrical, mechanical, and chemical energy.

• Chemical energy stored within molecular bonds is released when those bonds are broken via enzymatic oxidation.

• Cellular Respiration: A set of metabolic pathways that transfers energy from nutrient molecules (primarily glucose) to construct Adenosine Triphosphate (ATP).

  • During glucose oxidation, $40\%$ of released energy is captured as chemical energy in ATP molecules.

  • The remaining $60\%$ of released energy escapes as heat, which maintains internal homeostatic body temperature ($37\,^\circ\text{C}$ or $98.6\,^\circ\text{F}$).

Structure and Dynamics of ATP

• ATP is the primary cellular energy currency and consists of three distinct chemical units:

  1. An adenine nitrogenous base.

  2. A ribose 5-carbon sugar.

  3. A chain of three phosphate groups linked in sequence.

• The second and third phosphate linkages represent high-energy bonds ($\sim$). Breaking the terminal high-energy phosphate bond releases usable energy for cellular work, converting ATP into Adenosine Diphosphate (ADP) and an inorganic phosphate group ($\text{P}_i$).

• Phosphorylation: Re-attaching an inorganic phosphate group to ADP to regenerate ATP. This process requires an energy input derived from cellular respiration.

Overview of Cellular Respiration Stages

• Complete catabolism of glucose requires oxygen ($\text{O}_2$) and yields carbon dioxide ($\text{CO}_2$), water ($\text{H}_2\text{O}$), ATP, and heat:

$\text{C}_6\text{H}_{12}\text{O}_6 + 6\text{O}_2 \rightarrow 6\text{CO}_2 + 6\text{H}_2\text{O} + 32\,\text{ATP} + \text{Heat}$

1. Glycolysis (Anaerobic Phase)

• Occurs within the cytoplasm (cytosol) and does not require oxygen.

• Consists of a 10-step enzymatic sequence that breaks down one 6-carbon glucose molecule into two 3-carbon pyruvic acid molecules.

• Divided into three distinct phases:

  1. Phase 1 (Priming): Glucose is phosphorylated twice using energy from $2\,\text{ATP}$ molecules, producing fructose-1,6-diphosphate.

  2. Phase 2 (Cleavage): Fructose-1,6-diphosphate is split into two 3-carbon molecules (dihydroxyacetone phosphate and glyceraldehyde phosphate).

  3. Phase 3 (Oxidation and ATP Formation): High-energy hydrogen atoms and electrons are transferred to two $\text{NAD}^+$ carrier molecules to form two $\text{NADH} + \text{H}^+$. Subsequent steps yield four ATP molecules via substrate-level phosphorylation, resulting in a net gain of 2 ATP per glucose.

• Anaerobic Pathway (Lactic Acid Formation): In the absence of oxygen ($\text{O}_2$), $\text{NADH} + \text{H}^+$ donates high-energy electrons and hydrogen protons directly back to pyruvic acid, reducing it to lactic acid. Lactic acid accumulation inhibits glycolysis and causes muscle fatigue.

2. Citric Acid Cycle / Krebs Cycle (Aerobic Phase)

• Occurs within the mitochondrial matrix and requires oxygen.

• Preparatory Step: Each 3-carbon pyruvic acid enters the mitochondrion, loses a carbon atom (released as $\text{CO}_2$), and generates $\text{NADH} + \text{H}^+$ to form a 2-carbon acetyl group that combines with Coenzyme A (CoA) to produce acetyl coenzyme A (acetyl CoA).

• Cycle Mechanics: Acetyl CoA combines with 4-carbon oxaloacetic acid to form 6-carbon citric acid.

• Through a series of sequential reactions, citric acid is converted back into oxaloacetic acid to repeat the cycle.

• For each turn of the cycle (two turns per glucose molecule):

  • Releases $2\,\text{CO}_2$ molecules.

  • Generates $1\,\text{ATP}$ molecule directly.

  • Transfers hydrogen atoms and high-energy electrons to three $\text{NAD}^+$ molecules (forming $3\,\text{NADH} + \text{H}^+$) and one $\text{FAD}$ molecule (forming $1\,\text{FADH}_2$).

3. Electron Transport Chain / Oxidative Phosphorylation (Aerobic Phase)

• Occurs across enzyme complexes embedded within the inner mitochondrial membrane (cristae).

• High-energy electron carriers ($\text{NADH}$ and $\text{FADH}_2$) deliver high-energy electrons and hydrogen protons to the electron transport chain.

• As electrons pass through a cascade of electron carrier complexes, released energy powers the proton-pumping active transport of hydrogen ions, driving ATP synthase to phosphorylate ADP into ATP.

• At the termination of the chain, electrons combine with hydrogen protons ($\text{H}^+$) and oxygen ($\text{O}_2$) to form water ($\text{H}_2\text{O}$). Oxygen serves as the final electron acceptor:

$2\text{e}^- + 2\text{H}^+ + \frac{1}{2}\text{O}_2 \rightarrow \text{H}_2\text{O}$

• Summary of ATP Yield per Glucose Molecule:

  • Glycolysis: $2\,\text{ATP}$

  • Citric Acid Cycle: $2\,\text{ATP}$

  • Electron Transport Chain: $28\,\text{ATP}$

  • Total Yield: Up to $32\,\text{ATP}$ (or 36 ATP in select cell types depending on electron shuttle mechanisms).

Alternate Pathways and Carbohydrate Storage

• Monosaccharides derived from dietary carbohydrates can enter catabolic pathways to generate ATP, or enter anabolic pathways when cellular energy levels are saturated:

  • Glycogen: Excess glucose is polymerized into glycogen for storage, concentrated primarily within liver and skeletal muscle cells.

  • Triglycerides: Continued excess glucose is converted into glycerol and fatty acids to be stored as fat in adipose tissue.

DNA Structure, Replication, and Protein Synthesis

• Deoxyribonucleic Acid (DNA): The master genetic material storing nucleotide sequences that instruct cells how to synthesize specific proteins.

  • Proteins coded by DNA include enzymes, blood proteins, structural proteins of muscle and connective tissues, antibodies, and membrane receptors.

• Genome Definitions:

  • Gene: A sequence of DNA nucleotides containing instructions for producing one specific protein.

  • Genome: The complete set of genetic instructions in a single cell.

  • Exome: The small protein-coding portion of the human genome (approximately $1.5\%$ of the complete genome).

  • Gene Expression: The mechanism controlling which proteins are produced in a given cell type, in what quantities, and under what conditions.

Structural Organization of DNA

• DNA is a double-stranded molecule arranged as an antiparallel double helix.

• Each strand consists of a repeating backbone of sugar (deoxyribose) and phosphate groups.

• Nucleotide: The monomeric unit of DNA, consisting of one 5-carbon deoxyribose sugar, one phosphate group, and one nitrogenous base.

• Nitrogenous Bases:

  • Purines: Adenine (A) and Guanine (G) (two-ring structures).

  • Pyrimidines: Thymine (T) and Cytosine (C) (single-ring structures).

• Complementary Base Pairing: Nitrogenous bases on opposite strands bind via hydrogen bonds: Adenine pairs exclusively with Thymine (A-T via 2 hydrogen bonds), and Cytosine pairs exclusively with Guanine (C-G via 3 hydrogen bonds).

• DNA molecules wrap tightly around globular histone proteins to condense into chromatin and individual chromosomes.

DNA Replication

• Occurs during the S phase (Synthesis phase) of interphase prior to cell division.

• Steps in replication:

  1. Hydrogen bonds between complementary base pairs break.

  2. The double helix unwinds and unzips to expose two single template strands.

  3. DNA Polymerase brings in free complementary nucleotides to pair with exposed template bases.

  4. Ligases and associated enzymes form the sugar-phosphate backbones, creating two identical daughter DNA molecules, each containing one original strand and one newly synthesized strand (semi-conservative replication).

RNA Structure vs. DNA Structure

• Ribonucleic Acid (RNA) differs structurally from DNA:

  • Consists of a single polynucleotide strand.

  • Contains the 5-carbon sugar ribose instead of deoxyribose.

  • Uses the pyrimidine base Uracil (U) in place of Thymine (T). Uracil pairs complementarily with Adenine (A-U).

  • RNA molecules are significantly shorter than DNA genomic strands.

• Three major functional classes of RNA: Messenger RNA (mRNA), Transfer RNA (tRNA), and Ribosomal RNA (rRNA).

Protein Synthesis Mechanisms

Transcription (Occurs in Nucleus)

1. RNA Polymerase binds to a promoter DNA sequence at the start of a gene.

2. RNA polymerase unwinds and separates the two strands of the DNA double helix.

3. The enzyme moves along the exposed template DNA strand, catalyzing the synthesis of a complementary messenger RNA (mRNA) strand.

4. Synthesis continues until RNA polymerase reaches a termination signal sequence on the gene.

5. The newly synthesized mRNA strand is released, the original DNA helix rewinds, and the mRNA exits the nucleus via a nuclear pore to enter the cytoplasm.

Translation (Occurs in Cytoplasm)

• Genetic Code: The linear sequence of 3-base mRNA combinations called codons. There are 64 total codons:

  • 61 codons code for specific amino acids.

  • AUG is the universal start codon, coding for Methionine and initiating translation.

  • Three codons (UAA, UAG, UGA) are stop codons that signal the termination of translation and carry no corresponding tRNA.

• Translation Sequence:

  1. The mRNA strand binds to a ribosome (composed of rRNA and structural proteins).

  2. A Transfer RNA (tRNA) molecule carrying a specific amino acid approaches the ribosome. The tRNA contains a 3-base sequence called an anticodon complementary to the mRNA codon.

  3. The first tRNA anticodon pairs with the start codon (AUG) on mRNA.

  4. A second tRNA carrying its designated amino acid binds to the adjacent codon.

  5. Peptide bond formation is catalyzed between the adjacent amino acids.

  6. The first tRNA releases its amino acid, detaches from mRNA, and returns to the cytoplasm to be reloaded.

  7. The ribosome translates down the mRNA strand codon by codon, elongating the polypeptide chain until a stop codon is encountered.

  8. The completed polypeptide is released, folding into its active 3D protein conformation.

Mutations and Genetic Variations

• The base sequences of the human genome are $99.9\%$ identical among all people. The remaining $0.1\%$ structural variation accounts for individual health differences, physical appearance, and benign single nucleotide polymorphisms.

• Mutation: Any change in the DNA nucleotide sequence due to replication errors or chemical alterations.

  • Spontaneous Mutations: Arise randomly from insertion of unstable bases during replication.

  • Induced Mutations: Result from exposure to mutagens, such as ionizing radiation, UV light, or toxic chemicals.

• Pathological Effects of Mutations:

  • Mutations altering amino acid sequences can cause production of nonfunctional or missing proteins.

  • Sickle Cell Disease: Caused by a single nucleotide substitution in the hemoglobin gene, replacing glutamic acid with valine. Under low-oxygen conditions, the mutated hemoglobin alters red blood cell shape into a rigid sickle morphology, causing vascular blockages and severe pain.

• Protective Genetic Features:

  • DNA Repair Enzymes: Scan DNA molecules to cut out and correct mispaired or damaged bases.

  • Degeneracy of Genetic Code: Multiple codons code for the same amino acid (e.g., 2 to 4 codons per amino acid), meaning third-base mutations often produce identical amino acids without altering protein function.

  • Diploid Duplication: Humans possess two copies of each chromosome; a normal allele on one chromosome can often produce sufficient functional protein to compensate for a mutated allele.

Tissues

Histology and Intercellular Junctions

• Tissue: A specialized group of similar cells working together to perform a specific, shared physiological function.

• Histology: The microscopic study of tissues.

• The human body contains four primary tissue categories: Epithelial, Connective, Muscle, and Nervous tissues.

Intercellular Junctions

• Many cell types are tightly bound together by specialized intercellular junctions:

  • Tight Junctions: Formed by the direct fusion of adjacent cell membranes, closing extracellular spaces to prevent passage of substances between cells (e.g., lining of the small intestine).

  • Desmosomes: Structural "spot welds" formed between cell membranes that reinforce mechanical integrity against stretch (e.g., outer skin epidermal layer).

  • Gap Junctions: Tubular membrane channels (connexons) bridging adjacent cells that allow direct exchange of ions, nutrients, and small chemical signals (e.g., cardiac muscle cells and smooth muscle of the digestive tract).

• Nanotechnology Application: Structures sized under $100\,\text{nm}$ utilize liposomes (phospholipid bubbles) to encapsulate drugs (e.g., anesthetics, chemotherapeutics, or inhaled insulin), enabling targeted transport across the protective tight junctions of the blood-brain barrier.

Epithelial Tissues

• General Characteristics:

  • Cover organ surfaces, line body cavities and hollow organs, and form glandular tissues.

  • Always possess a free (apical) surface exposed to an open space and an anchored basement membrane attached to underlying connective tissue.

  • Lack blood vessels (avascular); nutrients diffuse upward to epithelial cells from dermal or underlying connective tissue blood vessels.

  • Cells are tightly packed and divide readily, allowing rapid wound healing.

  • Classified according to cell shape (squamous, cuboidal, columnar) and layer count (simple, stratified, pseudostratified).

Specific Epithelial Classes

1. Simple Squamous Epithelium

• Single layer of thin, flattened cells fitted tightly together.

• Functions in rapid filtration, diffusion, and osmosis.

• Found lining the air sacs (alveoli) of lungs, capillary walls, blood and lymph vessel linings, and membranes covering internal viscera.

2. Simple Cuboidal Epithelium

• Single layer of cube-shaped cells with centrally located, spherical nuclei.

• Functions in secretion and absorption.

• Found lining kidney tubules, thyroid follicles, and ducts of specific glands; covers ovary surfaces.

3. Simple Columnar Epithelium

• Single layer of elongated cells with oval nuclei located near the basement membrane.

• Specialized features include surface microvilli (to expand absorptive surface area), cilia, and mucus-secreting goblet cells.

• Functions in protection, secretion, and absorption.

• Found lining the stomach, uterus, and small and large intestines.

4. Pseudostratified Columnar Epithelium

• Single layer of elongated cells that appears stratified because nuclei are positioned at two or more levels. All cells physically touch the basement membrane, though not all reach the free surface.

• Commonly possess surface cilia and interspersed goblet cells.

• Functions in protection and sweeping mucus and debris out of airways.

• Found lining respiratory tract passages.

5. Stratified Squamous Epithelium

• Many cell layers; deep basal cells divide actively, pushing older cells outward toward the surface, where they become flattened.

• Keratinized Stratified Squamous: Outer epidermal skin layers accumulate the tough, waterproof protein keratin, causing cells to dry out, harden, and die.

• Non-keratinized Stratified Squamous: Lines moist internal cavities requiring physical protection against friction, such as the oral cavity, esophagus, vagina, and anal canal.

6. Stratified Cuboidal Epithelium

• Consists of 2 to 3 layers of cube-shaped cells lining a lumen.

• Provides reinforced protection.

• Lines larger ducts of mammary glands, sweat glands, salivary glands, and the pancreas.

7. Stratified Columnar Epithelium

• Consists of several cell layers; superficial cells are columnar, while deeper basal layers consist of cuboidal cells.

• Functions in protection and secretion.

• Found lining portions of the male urethra and larger excretory gland ducts.

8. Transitional Epithelium (Uroepithelium)

• Multi-layered tissue adapted to undergo physical stretch and alteration in shape in response to fluid tension.

• Consists of cuboidal and rounded cells that flatten out when stretched, forming a leak-proof barrier.

• Found lining the urinary bladder, ureters, and superior portion of the urethra.

Glandular Epithelium and Exocrine Secretion

• Composed of specialized cells that produce and secrete substances into ducts or tissue fluids.

• Endocrine Glands: Ductless glands that secrete chemical products (hormones) directly into tissue fluid or blood.

• Exocrine Glands: Glands that secrete products into ducts opening onto an internal or external surface.

Structural Classification of Exocrine Glands

• Unicellular Glands: Single-celled glands, such as mucus-secreting goblet cells.

• Multicellular Glands: Composed of many cells, sub-classified by structural architecture:

  • Simple Glands: Ducts do not branch before reaching secretory units.

  • Simple Tubular: Straight tube-like gland (e.g., intestinal glands).

  • Simple Branched Tubular: Multiple tubular secretory units converge into a single duct (e.g., gastric glands).

  • Simple Coiled Tubular: Long coiled tube ending in a single duct (e.g., merocrine sweat glands).

  • Simple Branched Alveolar: Sac-like expanded secretory units sharing a duct (e.g., sebaceous glands).

  • Compound Glands: Ducts branch repeatedly before reaching secretory portions.

  • Compound Tubular: Repeatedly branching ducts terminating in tubes (e.g., bulbourethral glands).

  • Compound Alveolar: Repeatedly branching ducts terminating in sac-like alveoli (e.g., mammary glands).

Modes of Exocrine Secretion

• Merocrine (Eccrine) Glands: Cells release fluid products through exocytosis without losing cellular material (e.g., salivary glands, merocrine sweat glands, pancreas).

• Apocrine Glands: Cells lose small portions of their glandular cell bodies during secretion (e.g., mammary glands, ceruminous wax glands).

• Holocrine Glands: Entire cells loaded with secretory products disintegrate and rupture to release their contents (e.g., sebaceous glands).

Connective Tissues

• General Characteristics:

  • Most abundant tissue type by weight.

  • Cells are separated by an abundant extracellular matrix (ECM) consisting of protein fibers and a fluid-to-solid ground substance.

  • Highly vascularized (with exceptions like cartilage) and capable of division.

  • Functions: Binds structures together, provides support and structural framework, protects organs, fills spaces, stores fat, produces blood cells, defends against infection, and repairs damaged tissue.

Connective Tissue Cell Types

1. Fibroblasts: The most common fixed cell type. Large, star-shaped cells that synthesize and secrete protein fibers into the ECM.

2. Macrophages (Histiocytes): Wandering phagocytic cells derived from monocytes. Move through connective tissues to clear foreign debris and pathogens.

3. Mast Cells: Large, fixed cells located near blood vessels. Release heparin (an anticoagulant preventing blood clotting) and histamine (a vasodilator promoting inflammation).

Connective Tissue Fiber Types

• Collagenous (White) Fibers: Thick, parallel threads of the structural protein collagen. Possess flexible structure with immense tensile strength. Main components of tendons and ligaments.

• Elastic (Yellow) Fibers: Branched bundles of the protein elastin. Highly elastic; can stretch easily and resume their original shape. Found in vocal cords and respiratory passages.

• Reticular Fibers: Very thin, highly branched collagenous fibers that form delicate supportive networks (stroma) within soft organs like the spleen and liver.

Connective Tissue Categories

Connective Tissue Proper

1. Loose Connective Tissue:

   • Areolar Connective Tissue: Forms delicate membranes composed of fibroblasts, collagen, and elastic fibers suspended in a gel-like ground substance. Located beneath epithelia, nourishing avascular epithelial layers.

   • Adipose Tissue (Fat): Specialized tissue where adipocytes store fat droplets in their cytoplasm, pushing nuclei to the periphery. Cushions joints, insulates, and stores metabolic energy. Located beneath the skin, behind eyeballs, around the heart and kidneys.

   • Reticular Connective Tissue: Composed of a network of thin reticular fibers providing a structural framework for soft internal organs (liver, spleen).

2. Dense Connective Tissue:

   • Dense Regular Connective Tissue: Contains densely packed, parallel bundles of collagenous fibers with few fibroblasts. Possesses high tensile strength to withstand pulling forces in a single direction. Forms tendons and ligaments. Lacks a direct blood supply, leading to slow wound healing.

   • Dense Irregular Connective Tissue: Consists of thick, randomly interwoven collagenous fibers capable of sustaining tension exerted from multiple directions. Found in the deep reticular layer of the dermis and surrounding skeletal muscles.

   • Elastic Connective Tissue: Contains abundant yellow elastic fibers. Provides elastic flexibility to the spinal column attachments, walls of hollow internal organs, large arteries, and respiratory airways.

Specialized Connective Tissues

1. Cartilage:

   • Rigid connective tissue providing support, protection, and structural framework.

   • Chondrocytes (cartilage cells) reside within small chambers called lacunae, completely surrounded by an extracellular matrix composed of collagen fibers and a gel-like ground substance.

   • Avascular; receives nutrients via diffusion from a surrounding connective tissue membrane called the perichondrium. Heals slowly when injured.

   • Hyaline Cartilage: Most common type; contains fine collagen fibers. Found on the ends of bones in joints, the soft part of the nose, respiratory rings, and embryonic skeleton models.

   • Elastic Cartilage: Rich in elastic fibers; provides flexible framework for the external ear and parts of the larynx.

   • Fibrocartilage: Extremely tough tissue containing dense bundles of collagenous fibers. Acts as a shock absorber between intervertebral discs, the pelvic girdle, and knee menisci.

   • Collagen Pathologies: Chondrodysplasia (asymmetric, widened collagen chains cause stunted growth and deformed joints); Marfan Syndrome (inherited deficiency of the protein fibrillin causing long limbs, weak aortic walls, and lens dislocation).

2. Bone (Osseous Tissue):

   • The most rigid connective tissue; matrix contains mineral salts (calcium phosphate and carbonate) deposited around collagen fibers.

   • Supports body structures, protects cranial and thoracic organs, acts as a lever system for movement, stores minerals, and houses blood-forming red bone marrow.

   • Osteocytes (bone cells) reside within lacunae arranged in concentric rings called lamellae surrounding a central canal containing blood vessels.

   • Osteon: The cylinder-shaped functional unit of compact bone formed by concentric lamellae, osteocytes, and a central canal.

   • Canaliculi: Tiny canal systems radiating through the bone matrix, allowing osteocyte cellular processes to connect and transport nutrients directly between central canals.

   • Spongy Bone: Interior bone tissue composed of delicate bony plates (trabeculae) containing osteocytes, reducing bone weight while housing marrow.

3. Blood:

   • Liquid connective tissue consisting of formed elements suspended in a fluid extracellular matrix called plasma.

   • Formed elements include Red Blood Cells (erythrocytes for gas transport), White Blood Cells (leukocytes for immune defense), and Platelets (thrombocytes for blood clotting).

Tissue Membranes

• Epithelial membranes are composite sheets composed of an epithelial layer underlaid by connective tissue.

• Four major types:

  1. Serous Membranes: Line internal body cavities that do not open to the outside (e.g., pleural, pericardial, peritoneal cavities). Composed of simple squamous epithelium and areolar connective tissue. Secrete watery serous fluid to lubricate organ surfaces.

  2. Mucous Membranes: Line cavities and tubes that open to the outside of the body (e.g., digestive, respiratory, urinary, and reproductive tracts). Composed of various epithelia over lie areolar tissue; contain goblet cells secreting mucus.

  3. Cutaneous Membrane: The external body covering commonly called the skin.

  4. Synovial Membranes: Composed entirely of connective tissue; line joint cavities.

Muscle and Nervous Tissues

Muscle Tissues

• Muscle cells (muscle fibers) are contractile and excitable, capable of shortening to generate movement.

• Skeletal Muscle Tissue: Attached to bones. Controlled voluntarily. Fibers are long, cylindrical, thread-like, multinucleated, and feature light and dark cross-markings called striations.

• Smooth Muscle Tissue: Non-striated, involuntary tissue. Cells are short, spindle-shaped, and contain a single, centrally located nucleus. Located in the walls of hollow internal organs (stomach, intestines, blood vessels).

• Cardiac Muscle Tissue: Found exclusively in the heart wall. Controlled involuntarily. Cells are branched, striated, single-nucleated, and joined end-to-end by specialized junctional complexes called intercalated discs.

Nervous Tissue

• Located in the brain, spinal cord, and peripheral nerves.

• Neurons: Highly specialized functional cells that receive, integrate, and conduct electrochemical impulses. Possess a central cell body (soma), receptive dendrites, and a single conducting axon.

• Neuroglia: Supportive helper cells that nourish, insulate, protect, and support neurons.

• Tissue Engineering: Biomedical technology growing replacement tissues on synthetic scaffolds using autologous stem/progenitor cells (e.g., regenerating donor urinary bladders from a patient's own smooth muscle and uroepithelium progenitor cells).

Integumentary System

Structure of the Skin and Layers

• The skin (cutaneous membrane) and its accessory structures (hair, nails, glands, sensory receptors) constitute the integumentary system.

• Skin is the body's largest organ by weight and contains two primary layers:

  1. Epidermis: The outer layer composed of stratified squamous epithelium.

  2. Dermis: The deeper layer, thicker than the epidermis, composed of connective tissue containing collagenous and elastic fibers, muscle, blood vessels, and nervous tissue.

• Subcutaneous Layer (Hypodermis): Located deep to the dermis. Consists of loose areolar and adipose connective tissue that insulates the body and contains major blood vessels. Not considered a structural component of true skin.

Layers of the Epidermis

• The epidermis lacks internal blood vessels (avascular). Basal cells are nourished via diffusion from dermal capillaries.

• As basal cells divide and grow, older cells (keratinocytes) are pushed outward away from the dermal nutrient supply. As they migrate, they undergo keratinization (hardening, dehydration, and filling with fibrous keratin protein).

• Tightly packed keratinocytes develop desmosomes and reach the surface to form the stratum corneum, eventually sloughing off.

• Epidermal thickness ranges from $0.07\,\text{mm}$ to $0.12\,\text{mm}$ across most of the body, but reaches $0.8\,\text{mm}$ to $1.4\,\text{mm}$ on the palms and soles.

Specialized Epidermal Cells

• Dendritic (Langerhans) Cells: Located in the stratum spinosum; phagocytes that defend against microbial invasion.

• Tactile (Merkel) Cells: Located in the stratum basale; associate with sensory nerve endings to form tactile discs for sensing light touch.

• Melanocytes: Specialized cells in the stratum basale that synthesize the pigment melanin inside organelles called melanosomes.

  • Melanocytes extend long cellular processes between neighboring keratinocytes, transferring melanin granules to protect keratinocyte nuclei from UV-induced DNA damage.

Skin Pigmentation Factors

• Melanin pigments:

  • Eumelanin: Brownish-black pigment standard in epidermis and hair.

  • Pheomelanin: Reddish-yellow pigment found in specialized regions (e.g., lips).

• Factors controlling skin color:

  • Genetic Factors: All humans possess roughly the same total number of melanocytes per unit area; skin color variations result from genetically controlled differences in the amount, size, and distribution of melanin granules.

  • Albinism: An inherited genetic mutation in melanin synthesis genes causing a complete lack of melanin pigment.

  • Environmental Factors: Sunlight exposure, UV lamps, and X-rays stimulate increased melanin synthesis (tanning).

  • Physiological Factors: Blood oxygenation in dermal vessels (high oxygenation appears pink; low oxygenation causes a bluish tint called cyanosis); dermal blood vessel dilation or constriction; dietary carotene accumulation; jaundice (liver dysfunction causing bilirubin buildup).

• Skin Cancer Risk: Exposure to UV radiation causes cellular DNA damage.

  • Basal cell carcinoma and squamous cell carcinoma arise from epidermal epithelial cells.

  • Melanoma arises from melanocytes. Melanoma accounts for only $4\%$ of skin cancer cases, but causes $80\%$ of skin cancer deaths.

The Dermis and its Layers

• Average thickness of $1\,\text{mm}$ to $2\,\text{mm}$. Binds the epidermis to underlying tissues.

• Contains dermal papillae projecting upward between epidermal ridges, producing finger-print friction ridges.

• Divided into two layers:

  1. Papillary Layer: Superficial, thinner layer composed of loose areolar connective tissue. Houses dermal papillae, capillaries, and Tactile (Meissner's) corpuscles (light touch receptors).

  2. Reticular Layer: Deeper, thicker layer composed of dense irregular connective tissue with tough collagenous and elastic fibers. Houses Lamellated (Pacinian) corpuscles (deep pressure receptors), hair follicles, sweat glands, and sebaceous glands.

Accessory Structures of the Skin

Nails

• Protective coverings on the terminal ends of fingers and toes.

• Consist of three parts:

  • Nail Plate (Body): Visible, keratinized surface layer overlying the nail bed.

  • Nail Bed: Layer of surface epithelium beneath the nail plate.

  • Nail Matrix: Active growth region of dividing cells at the proximal end of the nail bed.

  • Lunula: White, half-moon-shaped region at the base of the nail plate overlying the thick nail matrix.

  • Cuticle: Proximal fold of stratum corneum extending over the nail plate base.

Hair Follicles

• Hair is present on all skin surfaces except the palms, soles, lips, nipples, and parts of the external reproductive organs.

• Hair Follicle: A tube-like depression of epidermal stem cells extending down into the dermis or subcutaneous layer.

• Hair Anatomy:

  • Hair Root: Portion of the hair embedded within the follicle beneath the skin surface.

  • Hair Bulb: The expanded deep base of the hair root containing dividing cells of the hair matrix.

  • Hair Papilla: Projection of dermal connective tissue containing blood vessels that nourish dividing hair cells.

  • Hair Shaft: Dead, highly keratinized cellular column extending beyond the skin surface.

• Arrector Pili Muscle: Smooth muscle bundle attached to each hair follicle. Contracts involuntarily in response to cold temperatures or emotional fear, pulling hair upright and producing "goosebumps".

• Hair Disorders:

  • Androgenic Alopecia: Common pattern baldness caused by lowered levels of testosterone (men) or estrogen (women). Hair stem cells remain intact in follicles, but functional progenitor cells are lost.

  • Alopecia Areata: Autoimmune disorder where antibodies attack hair follicles, causing patch hair loss.

Skin Glands

• Sebaceous Glands:

  • Holocrine glands associated with hair follicles.

  • Secrete an oily mixture of fatty material and cellular debris called sebum, which keeps hair and skin soft, pliable, and waterproof. Absent on palms and soles.

  • Acne Vulgaris: Inflammation of sebaceous glands stimulated by pubertal androgen production; clogged ducts trapped with sebum foster anaerobic bacterial infections.

• Sweat (Sudoriferous) Glands:

  • Exocrine glands originating as coiled tubes in the deep dermis or subcutaneous layer.

  • Merocrine (Eccrine) Sweat Glands: Most abundant sweat glands. Respond to elevated body temperature to cool the skin. Secrete watery sweat (water, salts, wastes) through surface pores located on the forehead, neck, and back.

  • Apocrine Sweat Glands: Open into hair follicles in the axillary and groin regions. Activate during emotional distress, pain, and sexual arousal. Secretions develop odor when metabolized by skin bacteria.

  • Ceruminous Glands: Modified sweat glands in the external acoustic meatus secreting ear wax (cerumen).

  • Mammary Glands: Modified sweat glands in breasts secreting milk.

Thermoregulation and Skin Functions

• Primary functions of skin: Physical protection against infection/water loss, sensory reception, waste excretion, Vitamin D synthesis initiation (activated by UV light to promote calcium absorption), and temperature regulation.

Mechanisms of Heat Loss and Thermoregulation

• The hypothalamus in the brain monitors deep body temperature against a set point of $37\,^\circ\text{C}$ ($98.6\,^\circ\text{F}$).

• Heat is produced as a byproduct of cellular metabolism in active tissues (liver, skeletal muscles, cardiac muscle).

• Four physical methods of heat loss through skin:

  1. Radiation: Primary heat loss method; infrared heat rays diffuse from warm skin into cooler environment.

  2. Conduction: Direct heat transfer from skin to cooler solid objects in physical contact.

  3. Convection: Heat transfer away from skin into circulating air currents.

  4. Evaporation: Sweat absorbs body heat and evaporates into surrounding air, carrying heat away.

Thermoregulatory Control Loop

• Hyperthermia Response (Body Temperature Above Set Point):

  1. Thermoreceptors detect elevated temperature and signal the hypothalamus.

  2. Hypothalamus triggers dermal blood vessel vasodilation, increasing peripheral blood flow to radiate heat outward.

  3. Deep internal blood vessels constrict.

  4. Merocrine sweat glands actively secrete sweat to induce evaporative cooling.

• Hypothermia Response (Body Temperature Below Set Point):

  1. Thermoreceptors signal the control center in the hypothalamus.

  2. Hypothalamus triggers dermal blood vessel vasoconstriction, reducing skin blood flow to conserve internal heat.

  3. Sweat glands remain inactive.

  4. If temperature continues dropping, the hypothalamus signals skeletal muscles to contract involuntarily (shivering), generating metabolic heat.

• Thermoregulatory Complications:

  • Hyperthermia: Abnormally high body temperature occurring on hot, humid days when sweat evaporation fails, causing dizziness, nausea, headache, and potential cardiovascular collapse.

  • Hypothermia: Abnormally low body temperature leading to confusion, lethargy, loss of reflexes, and multi-organ shutdown.

  • Fever: Immune response where phagocytes release chemical pyrogens, raising the hypothalamic set point to help destroy pathogens.

Wound Healing and Burn Severity

• Inflammation: Natural tissue response to injury or stress characterized by dermal blood vessel dilation and increased capillary permeability. Inflamed tissue displays four cardinal signs: redness, swelling, heat, and pain.

Wound Repair Process

• Shallow Cuts: Damage restricted to the epidermis causes surrounding epithelial cells to increase mitosis and migrate to fill the gap.

• Deep Wounds: Damage reaching the dermis or subcutaneous layer ruptures blood vessels:

  1. Escaping blood forms a blood clot composed of insoluble fibrin, blood cells, and platelets.

  2. The clot and dried tissue fluids dry into a protective scab.

  3. Fibroblasts migrate into the region, secreting dense collagenous fibers to bind wound edges together.

  4. Granulation Tissue forms, consisting of new blood vessel branches and clusters of fibroblasts.

  5. Phagocytic macrophages clean up dead cellular debris.

  6. Damaged epithelial tissue regenerates, the scab sloughs off, and excess collagenous fibers form a scar.

Burn Classification and Rule of Nines

• Superficial Partial-Thickness (1st Degree) Burn: Injures only the epidermis (e.g., mild sunburn). Characterized by erythema (redness), heat, and mild inflammation. Heals in days to weeks without scarring.

• Deep Partial-Thickness (2nd Degree) Burn: Destroys the epidermis and part of the underlying dermis (e.g., burn from hot liquid). Causes fluid-filled blisters. Stem cells surviving in deep hair follicles and glands regenerate skin; usually recovers without scarring.

• Full-Thickness (3rd Degree) Burn: Completely destroys the epidermis, dermis, and all accessory structures. Requires skin autografts or synthetic skin substitutes to heal.

• Rule of Nines: Clinical method dividing total adult body surface area into sections representing $9\%$ (or multiples of $9\%$) to estimate fluid replacement requirements and burn severity:

  • Anterior and Posterior Head and Neck: $9\%$ ($4.5\%$ anterior, $4.5\%$ posterior).

  • Anterior and Posterior Upper Extremities: $18\%$ ($9\%$ per complete arm; $4.5\%$ per side).

  • Anterior and Posterior Trunk: $36\%$ ($18\%$ anterior chest/abdomen, $18\%$ posterior back/buttocks).

  • Anterior and Posterior Lower Extremities: $36\%$ ($18\%$ per complete leg; $9\%$ per side).

  • Perineum (Perineal Region): $1\%$.

  • Total Body Surface Area: $100\%$.

Life-Span Changes in the Integumentary System

• Epidermal cell cycle slows; skin becomes scaly, thin, and develops localized pigment spots ("age spots").

• Dermis thins as collagen and elastin decline, producing skin sagging and wrinkling.

• Subcutaneous adipose layer shrinks, increasing sensitivity to cold ambient temperatures.

• Sebaceous glands produce less oil, resulting in dry skin.

• Melanocyte counts decline, causing hair to whiten and gray.

• Hair follicle counts decrease, leading to hair thinning.

• Nail growth slows and nails become brittle or impaired.

• Sensory receptors decline in density, reducing touch and temperature sensitivity.

• Dermal vasodilation/vasoconstriction and sweat gland response efficiency decline, impairing body temperature regulation.

• Skin capacity to synthesize active Vitamin D diminishes.