Cell and Tissue PDF

5. Cell and tissue 5.1. Structure of cell 5.1.1. Plasma membrane All cellular membrane share common underlying structure Phospholipid Amphipathic in nature bilayer ○ Hydrophilic head...

5. Cell and tissue 5.1. Structure of cell 5.1.1. Plasma membrane All cellular membrane share common underlying structure Phospholipid Amphipathic in nature bilayer ○ Hydrophilic head (polar) ○ Hydrophobic tail (non-polar) High mobility  Fluid in Lipid can move laterally nature Mosaic model ○ Membrane proteins are dispersed throughout the membrane Factors affecting fluidity: Increasing temperature Shorter hydrophobic fatty acid tail Increase the number of double bonds Less cholesterol Function 1. Compartmentalisation Define boundaries Allow specialised activities without external interference → independent regulation 2. Scaffold for biochemical activities 3. Providing a selectively permeable barrier Ion channels allow materials to move into/ out of cells 4. Act as receptors to detect external signals 5. Provide cell-to-cell contact, adhesion & communication 5.1.2. Membrane bounded organelles Organelle Structure Function Nucleus Enclosed by nuclear envelope Contain DNA to direct cellular Double membrane functions With nuclear pores Endoplasmic 1. Rough ER Protein synthesis (protein releases reticulum Flattened sheets of into cisternae of rER) membranes and tubules- Well-developed in protein synthesis Presence of ribosomes and secretory cells (e.g. exocrine bound to the cytosolic pancreatic cells) surface 2. Smooth ER Steroid synthesis (e.g. androgen Free of associated from Leydig cells of testis) ribosomes Lipid metabolism More tubular compared to Detoxification rough ER Calcium storage and release (e.g. sarcoplasmic reticulum in muscle cells) Golgi Modification, packing, and Stacked membranous cisternae with apparatus distribution of proteins and lipids vesicles  for secretion/ internal use ○ Cis-Golgi network The side facing the ER and receives the vesicles from it ○ Trans-Golgi network The side in which proteins and lipids are released as vesicles ○ In the lumen Protein and lipid modification e.g. Glycosylation of proteins: long proteins cleaved into smaller ones Mitochondria Double membrane Provide energy for the cell in form of ATP Involved in programmed cell death Lysosomes Membrane-bound vesicles Contain enzymes to degrade phagocytosed materials Destruction of organelles (recycling & digesting) Enzymes mostly activated under acidic conditions Peroxisomes Small membrane-bound vesicles Contain enzymes to break down (smaller than lysosomes) long fatty acids (H2O2 metabolism) & amino acids Commonly present in liver 5.2. Nucleus Only present in eukaryotic cell Store genetic information 5.2.1. Nuclear envelope Doubled Outer membrane Continuous with the membrane of ER membrane Lumen of Continuous with the lumen of ER nuclear envelope Nuclear Formed by fusion of outer & inner nuclear pores membrane Function: Passive diffusion of small molecules (sugar/ nucleotides/ amino acids) Import protein Export RNA & protein 5.2.2. Nucleolus Site for synthesis of ribosomal RNA (rRNA) Contains genes for encoding rRNAs For processing & assembling the ribosomal subunit ○ Ribosomal subunits = rRNA + ribosomal protein imported from the cytoplasm Assembled ribosomal subunits transport out of the nucleus Assembled as functional ribosomes for protein synthesis in cytoplasm Fibrillar centre (fc) Depot of inactivated RNA genes Dense fibrillar component (dfc) Pre-rRNA synthesis Early rRNA processing Granular component (gc) Contain ribosomal subunits in different stages of assembling  5.2.3. Nucleoplasm Heterochromatin Inactive in gene transcription Dark stained, highly compacted Euchromatin Active in gene transcription Pale stained, loosely packed Overview: movement of proteins through intracellular membrane system 1. Ribosomal subunit exported from the nucleus through nuclear pore 2. Formation of functional ribosome in cytoplasm 3. Most ribosome reside at endoplasmic reticulum 4. Protein synthesis 5. Synthesised protein transport through transport vesicles to Golgi apparatus for protein modification/ maturation 6. Final product a. Secreted (exocytosis) b. Stay inside the cell for intracellular use as lysosome/ vacuole 5.3. Cytoskeleton Non membranous  Function: Maintain cell shape Cell locomotion Cytokinesis Intracellular traffic of organelles Provide mechanical strength to cells 5.3.1. Microfilament Organisation Building block: actin Globular monomer: G-actin Polymer filament: F-actin (+) end elongate faster  Function Cell movement Interact with myosin → cytokinesis Change in cell shape Example Intestinal microvilli ○ Increase surface area ○ Do not move 5.3.2. Intermediate filament  Organisation Building block: rod-like protein x2 = dimer x4 = x2 dimer (in antiparallel manner) = tetramer xN tetramer = protofilament ○ Stronger than actin filament/ microtubules ○ Exhibit strain hardening under stress Function Bear tension Maintain cell shape Example Keratin: Withstand physical force Without keratin: Cells become fragile & prone to rupture → skin blistering 5.3.3. Microtubules Organisation Building block: tubulin dimer (alpha/ beta tubulins) Longitudinal rows: protofilament 13 microfilaments arranged side-by-side to form a hollow centre  Origin: microtubule-organising centre (MTOC) ○ Site of assembling ○ Anchor for centrosomes/ basal bodies (cilia/ flagella) Function & Separation of chromosomes during mitosis example ○ Microtubules form mitotic spindle Intracellular transport of organelles ○ Axonal transport ○ Movement of materials down the axon Cell locomotion & support ○ Ciliary & flagella movement Prevention Colchicine of ○ Bind to tubulin dimer → prevent polymerisation microtubular function into microtubules Taxol  ○ Bind to microtubules → prevent polymerisation Disrupt mitosis Affect dynamic process of mitotic spindle for chromosome separation 5.4. Epithelial tissue 5.4.1. Embryonic origin Ectoderm Epithelium of skin Mesoderm Kidney tubules, endothelium (blood/ lymph vessels), mesothelium (serous cavities) Endoderm Respiratory & gastrointestinal tracts Function: Protection (skin) Absorption & excretion (intestine) Secretion (glandular epithelium) Sensation (retina/ olfactory epithelium) Association with connective tissue: Basement membrane: Acellular Formed by secretion of both epithelium & connective tissue  Function: Attachment to connective tissues Guide cell migration for tissue repair Tissue-specific (e.g. act as filter in Bowman’s Capsule, kidney) Basal lamina Secreted from epithelial cells Type IV collagen Reticular lamina Secreted from fibroblasts in connective tissues Type III collagen Characteristics: Rest on the basement membrane Junctional complex Avascular ○ Depend on connective tissue for material exchange Exhibit functional & morphological polarity Contains cytokeratin (intermediate microfilament) ○ Resist stretching Little/ no intercellular matrix ○ Closely packed  5.4.2. Classification No. of Cell shape Function Example cell layer Simple Squamous Facilitate Lining of heart/ blood vessels/ lymphatics exchange of material, absorption, secretions Lining of peritoneal & pleural cavity Cuboidal Secretion, Ducts of glands/ kidney tubules excretion, absorption  Columnar Transportation of Epithelial lining of intestines & gallbladder fluids, secretion, absorption Ciliated columnar Epithelial lining of the fallopian tube Stratified Squamous For protection, (non- superficial layers keratinised) of squamous cells contain nuclei Squamous For protection, (keratinised) superficial layers contains rich in amount of keratin fibres but without any nuclei (dead cells)  Cuboidal Proteccion, Excretory duct of exocrine gland (sweat gland secretion, limited ducts/ salivary glands ducts) absorption (uncommon) Columnar Protection, Larynx, large duct of exocrine glands (mammary secretion gland duct) (uncommon) Transitional For protection, to ONLY in mammal’s urinary tract (ureter & urinary accommodate bladder) high degree of stretching Pseudostratified For protection, Confined to airways to respiratory system in ciliated columnar mucus mammals production, cilia Respiratory epithelium beat to sweat mucus (and trapped particles) out of the respiratory tract  5.4.3. Morphological polarity in epithelial cell Apical Microvilli Non-motile GI tract surface Finger-like/ hair-like projections Microfilament Actins present Cilia Motile Respiratory epithelia Microtubules Oviduct Lateral Junctional Tight junction/ Nearest to special aspect of cell surface complex Zonula occludens Tight seal between adj. cell (ZO) Restricting movement of substance Adhering junction/ Layer of protein inside plasma membrane that Zonula adherens attaches membrane protein & microfilaments (ZA) Composition: transmembrane glycoproteins, cadherins Provides physical strength Desmosomes Provide mechanical strength Interact with keratin intermediate filament  Gap junction For communication between adjacent cells Allow ions & small molecules to pass to neighbouring cells Basal surface Infolding present Involve in active absorption & secretion Example: Kidney tubules Striated duct in salivary gland  5.4.4. Glandular epithelium Exocrine gland: No. of Single cell gland Goblet cell secretory ○ Present in tracheal & intestinal epithelia cells Multicellular Structure Branchy Simple of gland (unbranched) Compound (branched) Shape Longitudinal section Cross section Nature of Mucous gland Flattened nuclei Salivary gland secretory Secrete glycoprotein product (mucin) Pale cytoplasm  Serous gland Round nuclei Pancreas Secrete protein/ enzyme (watery) Basophilic staining (stain preferentially with basic dyes) Mixed gland Serous + mucous Salivary gland gland Serous demilune = serous cells arrange as a cap on the mucous cell Method Merocrine secretion No loss cytoplasm Sweat gland of Secretion leaves by secretion exocytosis Apocrine secretion Production of Mammary gland membrane-bound vesicles Holocrine secretion Cell rupture & Sebaceous gland secrete secretory product 5.5. Connective tissue 5.5.1. Embryonic origin Origin of connective tissue: Mesenchyme ○ From mesoderm Function: Exchange of materials Support & binding of other tissues together ○ E.g.: epithelia, blood vessels, nerves Protection ○ Against infection, inflammation, immune response Wound healing ○ Involve collagen I & III Regulating behaviour of cells ○ Migration, proliferation, differentiation  5.5.2. Components A. Extracellular matrix Ground Hyaluronic acid Polysaccharide substances Viscous, slippery, good lubricant Proteoglycan Core protein + Glycosaminoglycan (GAG) Traps water Glycoprotein Adhesion proteins Links to components of ground substance & surface of cells (e.g. fibronectin, laminin, osteopontin) Fibrous Collagen fibre Type I collagen components Formed by fibroblasts Most abundant Provide flexibility with high tensile strength Appear as wavy fibre Reticular fibre Type III collagen (very fine fibrils) Formed by fibroblast Provide supporting mesh framework for soft organs (e.g. spleen, red bone marrow, liver, lymph node) Not visible under H&E staining Silver stain: → black/ brown PAS: → pink Elastic fibre Stretch & recoil Branching fibres with wavy appearance (when relaxed) Fresh elastic fibre: yellow Distribution: e.g. aortic wall, larynx, ligamentum flavum in vertebral column Marfan Syndrome: Autosomal dominant disorder Defect in gene encoding protein fibrillin-1 Elastic fibres are loosely arranged → losing the stretch & recoil ability Predominant in aorta, skin, ligaments ciliary zonular fibres of the lens Patients often exhibit tall stature with long limbs and fingers B. Cellular components Resident Fibroblast Most common in connective tissue cell Fibrocyte: less active form Synthesise collagen, elastic & reticular fibre, ground substance of ECM Response to tissue damage & synthesise new matrix Adipocytes Cell containing single lipid droplet which nuclei squeezed to periphery Synthesis & storage of fat Endocrine & thermal regulation 1. Unilocular adipose tissue (white) 2. Multilocular adipose tissue (brown)  Mesenchymal stem cells Transient Macrophage Phagocytic cells derived from monocytes in blood cell Either fixed or transient Engulf pathogen, dead cells, RBCs Defence & immune response Antigen-presenting cell Lymphocytes Mast cells Contains numerous secretory granules ○ Cellular granule: vasoactive & immunoreactive substances  (e.g. histamine/ heparin) Mediate inflammation & allergic reaction Very dense & obscure nucleus Plasma cells Developed from B-lymphocyte after activation Oval shape Cells with prominent Golgi apparatus & rER Nucleus in eccentric location & clock-faced Antibody production Granular leukocytes  5.5.3. Types of connective tissue A. Embryonic connective tissue Mucous connective tissue in umbilical cord B. Mature connective tissues Connective Loose Fine network of collagen/ elastic/ reticular fibre with ground tissue connective substance-filled space proper tissue Widely distributed under epithelia of body (lamina propria), dermis (more cell of skin than fibre ) Example: mesentery of intestine To support & binding Material exchange Immune & defence function  Dense Regular Dense parallel collagen fibres connective Withstand tensile force in one direction tissue Poorly vascularised (more fibre Attach muscle to bones (tendons)/ bone to bones than cell) (ligament) Irregular Large amount of collagen fibre ○ Provide high tensile/ elasticity Fibres arranged in random direction Superficial connective tissue sheaths of muscle & nerves, adventitia of large blood vessels, capsule of glands/ organs Specialised Adipose connective tissues Cartilage Bone Liquid connective tissue 5.6. Cell proliferation Cell division: Day 0-1 Zygote Day 3-4 Morula Totipotent ○ Able to generate extra-embryonic tissue & embryo Day 5-6 Blastocyst Inner cell membrane ○ Embryonic stem cell (pluripotent: stem cells capable of giving rise to several different cell types) Extraembryonic tissue Stem cell: Self renewal (divide & produce more stem cells) Undifferentiated cells Have the potential to differentiate into functional cell  Lgr stem cell Highly proliferative @ epidermal layer Lgr6 @ base of gastric gland Lgr5+ @ hair follicle Lgr5/6+ Quiescent stem cell: Slow-cycling stem cells In a state of cell cycle arrest Activated in response to injury/ tissue damage Senescence: Permanent cell cycle arrest Ageing causes senescence ○ Accumulation of senescent cells in old individuals in vivo Senescence causes ageing ○ Senescence of stem cell progenitor compartments drive tissue ageing ○ Genetic experiment in mice shows senescence is detrimental to healthy ageing  5.6.1. Cell cycle Interphase G1 phase (growth) Cells grow in size S phase (synthesis) DNA replication for two daughter cells G2 phase Cell checks error in DNA replication M phase Prophase Chromosomes become condensed → become visible (mitosis) Nuclear envelope breaks down Nucleolus disappear Cytoskeleton forms spindle fibre  Metaphase (prometaphase): spindle fibre attach to kinetochore Chromosomes line up along the equator Each sister chromatid attached to a spindle fibre originating from opposite poles Anaphase Sister chromatids are pulled apart under the contraction of spindle fibre Telophase Chromosomes decondense Nucleus envelope develop Cytokinesis Physical division of cell G0 phase (resting) Temporarily/ permanently stop dividing → entre quiescence phase 5.6.2. Molecular control of cell cycle Cyclin-Cdk complex: Protein that undergo cyclical pattern of synthesis & degradation for cell cycle regulation Cyclin-dependent kinases ○ Trigger specific events in the cell cycle (DNA replication & cell division) ○ Bind to cyclin by phosphorylation ○ Add phosphate group to target protein  Cyclin D Cdk 4/6 Trigger cells to move from G0 to G1 G1 to S-phase Cyclin E Cdk 2 Prepare for DNA replication in S-phase Cyclin A Cdk 2 Activate DNA replication in nucleus in S- phase Cyclin B Cdk 1 Assemble mitotic spindle Reorganise cytoplasm for mitosis 5.6.3. Regulation A. Regulation of Cyclin-Cdk activities 1. Periodic synthesis Regulated transcription of cyclins 2. Periodic degradation Regulated proteolysis of cyclins 3. Phosphorylation/ dephosphorylation by other kinases (add phosphate group) & phosphatases (remove phosphate group) 4. Cdk inhibitors CIP (Cdk interacting protein)/ KIP (kinase interacting protein) & INK4 Mediate DNA damage checkpoint control  B. Sequential activation of Cyclin/ Cdk Phase Cdk Cyclin Regulation G1 phase Cdk 4 Cyclin D Phosphorylate Rb, releasing E2F Promote G1 to S phase S phase Cdk 2 Cyclin A FacilitateDNA replication G2 phase Cdk1 Cyclin B Activate FoxM1 to promote mitotic gene Trigger chromatin condensation, spindle formation, nuclear envelope breakdown Rb: retinoblastoma protein E2F: transcription factor C. Mitosis promoting factor (MPF) MPF: regulator of cell cycle (transition from G2 to M phase) ○ Cdk1/ Cyclin B Wee1 (inhibitory kinase) phosphorylate Cdk1 → inactive Cdk1/cyclin B (G2 phase) Cdc25 (activating phosphatase) dephosphorylate & activates Cdk1 → activate downstream protein related to mitosis  D. Synthesis & degradation of cyclin Temporal availability of cyclins affect activation of MPF Synthesis Allow formation of Cyclin/Cdk complex Degradation Removal of Cyclin/Cdk complex to inactivate MPF E. Cyclin-dependent kinase inhibitors (CKIs) Cyclin/Cdk complex Inhibitor Phase affected Cyclin D/ Cdk4/6 INK4 G1 phase Cyclin E/ Cdk2 Cip/Kip (p21) G1 /S phase Cyclin A/ Cdk 2 Cip/Kip (p21) S phase Cyclin B/ Cdk1 Cip/Kip (p21/ p27) G2/ M phase INK4: inhibitor of kinase 4 CIP/ KIP: Cdk interacting protein/ kinase inhibitory protein DNA Damage-induced p53 and p21 synthesis: p53: activated in response to DNA damage through phosphorylation to stabilise it ○ Transcription factor regulating genes involved in cell cycle arrest/ repair/ apoptosis p21: inhibits cyclin/Cdk complexes (Cdk2/ Cdk1) ○ Stop cell cycle progression Dysregulation of cell cycle can cause cancer: 5.7. Skin  Largest organ in the body ○ Weight: 5 kg (70-kg, average build individual) ○ Body surface area: 2 m² Epidermis (stratified, cellular) Dermis (connective tissue) Subcutis (fat, skin appendages) Protects underlying structures (fascia, muscle) Development: Ectoderm + Mesoderm ○ Ectoderm: nervous system, epidermis ○ Mesoderm: dermis, skin appendages Hair follicles, nails (9 week) Sweat glands (9 week – palms, soles; 15 week – others) Sebaceous glands (15 week) 5.7.1. Function Mechanical barrier Prevention of physical injury Stratum corneum ○ Cornified cell envelope ○ Highly insoluble layer ○ Glutamyl-lysyl isodipeptide bonds ○ Rich in ceramides, free sterols, free fatty acid Prevent inward/ outward passage of water & electrolytes UV Protection Protection against DNA damage → mutations → carcinogenesis (epidermis, melanin) UV absorption ○ Stratum corneum ○ Epidermal keratinocyte ○ Melanin DNA repair mechanism Melanocytes ○ Pigment-producing cells ○ Located at basal epidermis ○ Production of melanin Eumelanin (brown/ black) Phaeomelanin (yellow/ red) ○ Melanin transferred as melanosomes Melanocytes → keratinocyte/ hair Thermoregulation Constant body core temperature (vessel + sweat gland) Independent on environmental changes Thermoreceptors (warm, cold-sensitive) Signal processing in hypothalamus  ○ Sweating ○ Shivering ○ Alteration of circulation Immunity Innate (innate, adaptive) ○ Antimicrobial peptides E.g. cathelicidins, beta-defensins Direct antimicrobial action ○ Alarmins Enhance host defence system Chemotactic, angiogenic ○ Phagocytosis Dermal dendritic cells Macrophages Adaptive immunity ○ Antigen-presenting Langerhans’ cells, dendritic cells, macrophages ○ Cellular immunity (Th1 response) ○ Humoral immunity (Th2 response) Sensation Afferent → sensory (touch, pressure, Efferent → autonomic temperature change, pain, Specialised sensory receptors: Meissner’s corpuscles/ Merkel’s itch) receptors Endocrine Production of vitamin D (Vitamin D synthesis) ○ Upon sunlight exposure Cholesterol → cholecalciferol (D3) Vitamin D: Fat-soluble Enhance intestinal absorption of Ca2+, PO43- Bone metabolism Deficiency: Ricket, osteomalacia, osteoporosis Communication Visual appeal, texture, smell Role in social and sexual aspects Organ of communication Enhancement by clothings, cosmetics  5.7.2. Structure Epidermis 0.05 – 0.1 mm in thickness 30-day cycle (basal surface) Cellular level: keratinocytes Stratified ○ Stratum corneum ○ Stratum granulosum ○ Stratum spinosum ○ Stratum basale Dermo-epidermal Complex network of protein and glycoprotein junction (DEJ) Basement membrane ○ Basal keratinocyte in contact with superficial dermis Importance: Adhesion (destruction → blister; e.g. pemphigoid) Cellular migration (wound healing) Cellular signalling (epithelial-mesenchymal) Dermis Supporting matrix Water retention Strength Involves proteins, ground substance and polysaccharides Rich in blood supply ○ Superficial & deep vascular plexus Adnexal structures  ○ Pilosebaceous unit, eccrine, apocrine glands Major protein fibre: Collagen (80-85% of dry weight) ○ For tensile strength Elastic tissues (elastin, microfibrils) (2-4% of dry weight) ○ Elasticity Dermal collagens ○ Type I, III: dermal interstitium ○ Type IV: basement membrane ○ Most collagen skincare products have molecules that are not small enough to pass through the DEJ Polysaccharides ○ 0.1 - 0.3% ○ Hyaluronic acid ○ Water-binding capacity ○ Water: 60% of dermis by weight Subcutis Adipose tissue 80% of body’s fat reserve Arterioles, venules, lymphatics Function: Calorie reserve Cushion effect Insulation Glabrous skin ○ Non-hair bearing → no acne vulgaris ○ Palms, soles have thickened skin ○ Compact stratum corneum (10 times > flexures) ○ Encapsulated sense organs (dermis) ○ Lack of hair follicles and sebaceous glands Hair-bearing skin ○ Hair follicles and sebaceous glands ○ Lack of encapsulated sense organs  5.7.3. Skin appendages Hair Hair follicle: Scalp ○ Terminal hair ○ Largest follicle size ○ Extension into subcutis ○ Grows around 1 cm/ month Forehead ○ Vellus hair ○ Small follicle size ○ Large sebaceous glands Number of follicles Remained unchanged until middle life Ratio of terminal hair : vellus hair changes Androgenetic alopecia ○ Hair loss due to premature conversion of terminal to vellus hair Hair growth: Anagen (growing) ○ Active growth phase ○ Up to 90% of hair follicles ○ Length of hair cycle: 2-7 years, average of 3 years Catagen (regressing/ transitional) ○ Regressing/ Involuting phase ○ ~1% of hair follicles  ○ Length of hair cycle: 3 weeks Telogen (resting) ○ Resting/ Quiescent phase ○ ~10% of hair follicles ○ Hair shedding occurs in the telogen phase ○ Length of hair cycle: 3 months E.g. Eyebrows complete hair cycle in 4 months Scalp hair: 100,000 terminal hair follicles on average Telogen phase ○ 10% of hair follicles – 10,000 ○ Lasts for around 3 months (100 days) ○ On average 100 hair shed per day (normal) Telogen effluvium ○ Due to physical or psychological stress ○ Up to 70% ot hair enter telogen phase prematurely Nail Nail development since 8-9 weeks of gestation Growth: Fingernails – 3 mm/ month Toe nails – 1 mm/ month Structure: Lunula – most distal portion of nail matrix Nail matrix – gives rise to nail plate Nail bed under nail plate Proximal nail fold Hyponychium  Function: Mechanical protection Enhance sensory discrimination Dexterity (scratching/ grooming) Cosmetic accessory Related disease: Acute paronychia ○ Water goes into nail bed, causes inflammation of nails ○ Due to topical agents or frequent hand washing Adnexal Pilosebaceous structure unit Originated from epidermal downgrowth Developed between 10–14 weeks of gestation 4 classes of hair:  Terminal (scalp, beard area) Vellus (majority of skin) Apopilosebaceous (axilla, groyne) Sebaceous (face, chest, back) Eccrine gland Thermoregulatory sweating Distributed nearly entire body surface Identifiable over palms, soles in 16th week Structure: Diameter: 30-50 um Length: 2-5 mm Bullous secretory coil (lower dermis) Secretory duct (dermis) Opening pore (surface) Stress leads to sweating in palms and soles Apocrine Secretion by “decapitation” gland Low secretory output Lipid rich production Connected to hair follicles Axilla, genitalia, mammary areas Human perspiration: Insensible perspiration ○ Passive water evaporation from skin surface ○ Depends on temperature, humidity  Active sweating (mainly eccrine glands) ○ Thermal (heat) → body temperature ○ Mental/ Emotional (mental stimuli) → palms, soles Nerve innervation: Sympathetic Cholinergic fibres Increased pilocarpine (increase sweat) Increased atropine (reduces sweat) Repair & renewal : Proliferation and differentiation Stem cells ○ Bulge area of follicles ○ Basal area of the interfollicular epidermis ○ Base of sebaceous glands 5.8. Homeostasis 5.8.1. Organisation of physiological function Level of organisation: Atoms & molecules Organelles Cells Tissues Organs Organ system Organism Cardiovascular system: Heart is made of cardiac muscles, epithelium, connective tissues Act as pump: contract & relax rhythmically (cardiac cycle) Deoxygenated blood: pumped to lungs for gas exchange Oxygenated blood: supplied to organs Adjust strength & frequency of contractions to meet metabolic needs Arteries: from heart to organs Vein: from organs to heart  Large arteries → smaller arteries → arterioles → capillaries Smooth muscle contract/ relax to change diameter of arteries/ arterioles to change amount of blood supplied to organ Organ system (interdependent nature): Circulatory system/ cardiovascular system (pumping blood) Respiratory system (O2/ CO2) Digestive system (nutrients & water) Urinary system (water & waste) Integumentary system (protective boundary, body temperature regulation)  Musculoskeletal system (support & body movement, blood cell production in bone marrow) Nervous & endocrine Reproductive system Immune system 5.8.2. Body fluid Water: 50-70% total human body weight Solvent for substances in body (e.g. ions, nutrients, gases) Medium for biochemical reactions Osmolality (Osm/kg) Number of osmoles per kilogram (mass) Osmolarity (Osm/L) Number of osmoles per litre (volume) Body fluid Intracellular Extracellular fluid (ECF) fluid (ICF) Interstitial fluid Blood plasma Fluid in space In blood around cell Transcellular fluid Within epithelial space Cerebrospinal fluid/ synovial fluid/ intraocular fluid/ pleural fluid Movement substances between ICF & ECF Water: via osmosis Ion: ✔ICF ←→ plasma ❌ICF ←→ ECF Protein: too large, ❌, only present in ICF & plasma ICF: higher [K+] ECF: higher [Na+/ Cl-] Internal environment Surrounded by ECF External environment Surrounded by the body 5.8.3. Homeostasis mechanism State of dynamic constancy Variables stay within narrow range/ change significantly throughout the day  Body act to restore variables to a set point [K+]: Too low Disrupt nerve impulse transmission → paralysis Too high Cardiac arrest Blood pressure: Pressure of blood against the lal of arteries Hypertension: high blood pressure Hypotension: low blood pressure Tachycardia: heart beat faster than 100 bpm Bradycardia: heart beat slower than 60 bpm Homeostasis control system: Sensor Sensory cells (thermoreceptors/ baroreceptors/ chemoreceptors/ osmoreceptors) Cellular components (cell surface receptors/ enzymes) Control centre Utilise electrical signals (action potential)/ chemical signal (neurotransmitter/ endocrine/ paracrine/ autocrine) to control effector Effector Blood pressure: heart/ blood vessels/ kidney Blood glucose level: liver/ adipose tissue/ skeletal muscle Blood volume & osmolarity: kidney/ blood vessel Neural mechanism: Endocrine mechanism: Neuroendocrine mechanism: Blood pressure homeostasis: Blood glucose: Properties: Property Neural mechanism Endocrine/ neuroendocrine mechanism  Speed Immediate response with Slower than neural, extra time rapid conduction velocity needed for hormone synthesis/ transport Specificity Localised effect Global effect Duration of Usually very short Last longer than neural action Negative feedback: Act to change the regulated variable towards normal level, eliminating stimulus detected by sensor Reduce variability of regulated variable Feedforward control (anticipatory response): unable to prevent changes from happening Positive feedback: Amplify input signal → accelerate the process E.g. coagulation cascade (prevention of bleeding), childbirth, surge of luteinising hormone after follicular phase of menstrual cycle 5.8.4. Thermoregulation Body temperature: Core temperature: 36-37.5°C (fluctuate ~1°C) Menstrual cycle cause slight fluctuation of core temperature in female Impact rate biochemical reactions & activity level Heat balance: Heat production Heat loss  By-product of metabolism To compensate significant proportion of Heat loss from skin surface: energy lost Heat transfer from internal body core to skin ○ Metabolism of nutrients via circulation ○ ATP → ADP + P Higher rate of blood flow to skin: promote Heat is produced mostly in internal body heat transfer from internal body core to skin core Means of heat loss: Factors affecting metabolic rate: Radiation Basal metabolic rate (for maintaining basic ○ Infrared rays function of all living cells) ○ Heat exchange between body & Additional metabolism environment ○ Increase muscle activity (shivering/ ○ Surrounding temp. > body temp.: exercise/ movement) heat gain by radiation ○ Thyroid hormone/ growth hormone ○ Epinephrine/ norepinephrine/ Conduction & convection sympathetic stimulation ○ Heat conducted to air through ○ Digestion/ absorption/ storage of contact with skin/ ventilation food/ nutrients (diet-induced ○ Heated air carried away & replaced thermogenesis) by convection (air current) Insulating property of skin: Evaporation Skin & subcutaneous tissues (fat is a poor ○ Heat lost when water evaporate from heat conductor) body surface Prevent heat loss from internal body core ○ Insensible water loss: water evaporate from skin/ lungs even when the person is not sweating Ways to prevent heat loss: Clothing (reduce conduction/ convection) Clothing traps air (reduce convection of air around skin surface) Emergency blanket (prevent heat loss by radiation) 5.8.5. Response to temperature change Receptor/ Central Preoptic area (POA), @ anterior (front) end of hypothalamus sensor thermoreceptor Detect core temperature Warmth-sensitive neuron ○ Firing rate (rate that neuron in brain generate electrical impulse) increase when body temperature increase Cold-sensitive neuron Skin thermoreceptor Detect change in ambient temperature  Cold receptor Warmth receptor Extreme cold/ heat stimulate pain receptor Effector Skeletal muscle Posterior hypothalamus Motor neuron Shivering Brown adipose tissue 1. Sympathetic noradrenergic neuron (BAT) ○ Norepinephrine Bind to Β3-adrenergic receptors on BAT 2. Thyroid hormone ○ Upregulate expression of UCP1 by BAT Breakdown TAG into FA & glycerol Energy release as heat (X ATP) Skin 1. Sympathetic cholinergic neuron ○ Acetylcholine 2. Adrenal medulla ○ Epinephrine/ norepinephrine Activate eccrine sweat gland Promote heat loss by evaporation 1. Sympathetic noradrenergic neuron ○ Norepinephrine Bind to α-adrenergic receptors of arterioles & arteriovenous anastomoses Vasoconstriction Increase in core body temperature Decrease in core body temperature Warmth-sensitive neuron in POA (send Cold-sensitive neuron in POA (send signals signals to posterior hypothalamus) to posterior hypothalamus) Inhibit sympathetic noradrenergic neuron Stimulate sympathetic noradrenergic neuron ○ Vasodilation ○ Vasoconstriction ○ Increase blood flow to skin ○ Decrease blood flow to skin ○ Increase heat loss by radiation/ ○ Decrease blood loss by radiation/ conduction conduction (Infants) inhibit sympathetic noradrenergic (Infants) stimulate sympathetic neuron noradrenergic neuron ○ Decrease heat production via ○ Increase heat production viz thermogenesis thermogenesis Stimulate sympathetic cholinergic neuron Stimulate motor neuron to induce shivering ○ Stimulate eccrine sweat gland  Exposure to high ambient temperature Exposure to low ambient temperature Skin warmth receptor Skin cold receptor Stimulate warmth-sensitive neuron in POA Inhibit warmth-sensitive neuron in POA Vasodilation Vasoconstriction (Infants) decrease heat production via (Infants) increase heat production via thermogenesis thermogenesis Newborns /infants X shiver/ sweat Small in size, high SA to volume ratio ○ Core temperature is more prone to change Modest ability to cause vasoconstriction of skin arterioles & AV anastomoses Large deposit of BAT Adults Can readily shiver/ sweat Can cause vasoconstriction of skin arterioles & AV anastomoses Minimal amount of BAT Elderly Less able to sense heat/ cold Reduced ability to generate/ dissipate heat 5.8.6. Fever, hyperthermia, hypothermia Fever (pyrexia) Increase in core body temperature due to elevation of thermoregulatory set point Cause Bacterial/ viral infection (most common) Physical trauma/ tissue damage In response to exogenous pyrogens (e.g. lipopolysaccharide from Gram-negative bacteria) Macrophages release cytokines (e.g. IL-1β, IL-6 and TNF-α) to the circulation ○ Increased production of prostaglandin E2 (PGE2) in the brain ○ PGE2 acts on the preoptic area to increase the set point Antipyretic drugs (aspirin/ ibuprofen) reduce fever by inhibiting the production of PGE2 Hyperthermia Increase in core body temperature above set point Cause Strenuous exercise ○ Increased skeletal muscle activity High ambient temperature ○ Increased heat gain from/ reduced heat loss to the environment High ambient humidity  ○ Decreased rate of evaporation of sweats Response Profuse sweating → heat exhaustion ○ The body loses water and salt weakness, nausea, fainting Heatstroke ○ Complete breakdown of thermoregulatory system (e.g. failure to sweat) → collapse, delirium seizure, prolonged unconsciousness Acclimatisation to heat (when a person is exposed to hot weather for an extended period) ○ Sweat more profusely → become better able to lose heat ○ Sweat with lower concentration of sodium chloride due to increased aldosterone secretion by adrenal cortex ○ Lose less salt from sweating → less likely to experience weakness due to excessive loss of salt Hypothermia Decrease in core body temperature below set point Cause Prolonged immersion in cold water ○ Water has greater specific heat capacity & thermal conductivity than air Alcohol intoxication ○ Ingestion of alcohol → vasodilation of skin blood vessels Response (Severe hypothermia) Impaired consciousness, cardiac arrest