Tissue Types in the HumanSiufui HendrawanBiochemisty and Biology MolecularSchool of Medicine - Tarumanagara University

Tissue Types in the HumanEpithelialPrimarily used for protectionVery little extracellular material between cellsEndothelium: specialized epithelial cells in blood vesselsConnectivePrimarily used for supportMusclePrimarily used for movementNervePrimarily used for control

Connective tissues

Tissues specialized for maintenance of integrity and support of organsMade from matrix proteins and cells in different composition and proportionsLoose, dense or specialized such as bone or cartilage

Type of Connective tissues

1. Loose connective tissue

Underlies epithelia in soft places such as GI tract and lungs Found around organs Few fibers, some cells, sparse ECM ECM of hyaluronan and proteoglycans supported by collagen and elastic fibers Cells mostly fibroblasts and migratory immune cells, adipocytes

2. Dense connective tissue

Lots of strong fibers, predominantly collagen Few cells, mostly fibroblasts Dependent on composition can be as hard as a bone or elastic as in skinCollagen can be arranged precisely such as in tendon or cornea or scattered as in skinDense connective tissue can also be elastic (collagen and elastic fibers) as in skin or large arteries

3. Specialized connective tissue: bone or cartilage

Connective TissueMatrix - non-living component of connective tissue = Extracellular Matrix (ECM): A collection of proteins and carbohydrates produced by cells that forms a matrix outside the cell Ground SubstanceProteoglycan aggregates (PGA) - pine tree shaped moleculesAdhesive proteinfibrilin, fibronectin, laminin

FibersCollagen, Elastin, and Reticular Fibers

Cells - living component of connective tissue

Two classes of connective tissue cells Indigenous Immigrant

Functions Produce extracellular matrix Defend against infections Storage of foodstuffs in form of easily accessible fats

Indigenous cells of connective tissue

Undifferentiated mesenchymal cells Proliferate and differentiate into fibroblasts , fat cells, chondrocytes Fibroblasts Synthesize most of ECM molecules (especially collagen) Mast cells

Adipocytes (white fat cells)Immigrant cells of connective tissue

Blood cellsAll derive from a stem cell in bone marrow

Extracellular Matrix (ECM):

Functions:Support (bone and cartilage)Integrate cells into tissues (adhesion)Influence cell shape and cell movementInfluence cell development and differentiation

Extracellular Matrix (ECM):

Proteoglycans

ProteoglycansComplex of a core protein and glycosaminoglycansGAGs are linear, repeating disaccharides with amine modificationsOften sulfatedAlways negativeThus, the hydrophilic GAGs spring away from one another, and form a hydrated matrix

Proteoglycans

Types of FibersFibrous protein in connective tissue structureConstitutes about 50% of the proteins in manPresent to some degree in all human organFormed of parallel fibrilsHigh modulus of elasticityMany types (e.g. type I)Major constituent of tendons

Collagen

Collagen is the major structural protein of vertebrate extracellular matrix. Types of collagen Collagen type I i)The fibers have diameter between 80 to 160nm. ii)Found in bone, dentin, skin, tendon, muscles and walls of blood vessels. Collagen type II i)have a diameter

SCANNING ELECTRON MICROGRAPH OF DENSE COLLAGEN FIBERS OF GINGIVA

Collagen acts as the support structure in tissues and facilitates the live and function of cells.

HEALTHY GINGIVA CONTAINS MANY FIBROBLASTS AND A FEW INFLAMMATORY CELLS SUCH AS MACROPHAGES ,NEUTROPHILS, PLASMA CELLS AND LYMPHOCYTES.

Collagena. protein high in content of AA, glycine, proline, hydroxyproline and many AA missing b. Protein helix is linearly oriented-3 chains twisted around each other in a fibril. H bonding between the chains.

The hierarchical design of collagen.The structural features of collagen ranges from the amino acid sequence, tropocollagen molecules, collagen fibrils to collagen fibers.

OtherTypes of FibersReticular Fibers: Actually very fine collagen fibersUsually form a networkFill space between other tissues & organsContained in the reticular laminae

Elastic Fibers:Contain protein called ELASTINElastin molecules look like coiled springsReturn to original shape after distortion

Collagen and elastin. Elastin polypeptide chains are cross-linked together to form rubberlike, elastic fibers.

Each elastin molecule uncoils into a more extended conformation when the fiber is tretched and recoils spontaneously as soon as the stretching force is relaxed.

Elastin is a protein in connective tissue that is elastic and allows many tissues in the body to resume their shape after stretching or contracting. Elastin serves an important function in arteries and is particularly abundant in large elastic blood vessels such as the aorta. Elastin is also very important in the lungs, elastic ligaments, the skin, the bladder, elastic cartilage

Elastin is primarily composed of the amino acids glycine, valine, alanine, and proline. It is a specialized protein with a molecular weight of 64 to 66 kDa, and an irregular or random coil conformation made up of 830 amino acids.

Elastin is made by linking many soluble tropoelastin protein molecules, in a reaction catalyzed by lysyl oxidase, to make a massive insoluble, durable cross-linked array. The amino acid responsible for these cross-links is lysine.

Disorders of connective tissueEhlers-Danlos syndrome - deficient type III collagen- a genetic disease causing progressive deterioration of collagens, with different EDS types affecting different sites in the body, such as joints, heart valves, organ walls, arterial walls, etc.

Marfan syndrome - a genetic disease causing abnormal fibrillin. Scurvy - dietary deficiency in vitamin C, leading to abnormal collagen. (hemorrhages, loose of teeth, gums swell and bleed easily)

Osteogenesis Imperfecta results in a dramatic weakening in the structure of bone, which leads to frequent fractures occurring at an early age. The fractures, in turn, lead to permanent deformaties of the extremities.

Diseases that Affect Collagen

Overproduction of Collagen FibersLung Fibrosis (Cystic Fibrosis) excess glandular secretions (mucous)Liver Cirrhosis irreversible scarring (fiber deposition) in the liver

Atherosclerotic heart disease

Insufficient CollagenEhlers-Danlos syndrome - rubber man - contortionist diseaseOsteogenesis Imperfecta - brittle bonesScurvey -Vitmain C deficiencyToo few hydrogen bonds in the formation of the collagen moleculeInferior tissue formation in bones, blood vessels, skin, and teeth

Autoimmune Disorders that Damage Collagen Lupus Erythematosus Collagen damage and inflammation - can occur anywhere in the body Most Common areas affected: skin, articular tissue, Some have inner organ problems (heart, lungs, kidneys, blood vessels, brain)

Diseases that Affect Collagen

Bone

Connective tissue that provides mechanical support and protectionMostly calcified matrix with few cellsVery important storage of calciumMechanical strength derived both from composition and overall organizationSpongy or compact

Chemistry of the bone

A. CellsB. Extracellular matrix - Osteoid uncalcified bone matrix - Mineral Organized in rounded structures called osteonsHighly vascular and well innervatedContains lymph channelsFunctions in mineral storage and blood cell production besides support, protection, and movementInfluences on Bone Growth:Levels of Ca++, Phosphorous, Vitamin D, HGH, estrogen, testosterone

Osteons

Principal organizing feature of compact bone Haversian canal place for the nerve blood and lymphatic vessels Lamellae collagen deposition layers Osteocytes (bone cells) localized in lacunae

A. Bone Cells

Osteocytes

Trapped osteoblasts Keep bone matrix in good condition and can release calcium ions from bone matrix when calcium demands increase Connected to each other by long filopodia that run through narrow channels in calcified matrix canalliculi

2. Osteoblasts Make collagen well developed secretory organelles Activate crystallization of hydroxyapatite onto the collagen matrix, forming new bone As they become enveloped by the collagenous matrix they produce, they transform into osteocytes3. Osteoclasts

Resorbe bone matrix from sites where it is deteriorating or not needed Multinucleated giant cells Focal decalcification and extracellular digestion by acid hydrolases and uptake of digested material

Bone contains both organic and inorganic material - Organic : Tropocollagen subunits giving bone elasticity and fracture resistance (osteoid) - Inorganic : 65% of bone weight is calcium hydroxyapatite, sodium, magnesium, carbonate, and fluoride (mineral)

B. Extracellular matrix of the bone

Osteoid

Collagen type I arranged in a mesh Layers of various orientations (add to the strength of the matrix) Other proteins 10% of the bone protein Mineral

A calcium phosphate/carbonate compound resembling the mineral hydroxyapatite Ca10(PO4)6(OH)2 Hydroxyapatite crystals Imperfect Contain Mg, Na, K

Mineralization of the bone

Calcification occurs by extracellular deposition of hydroxyapatite crystals - Trapping of calcium and phosphate ions in concentrations that would initiate deposition of calcium phosphate in the solid phase, followed by its conversion to crystalline hydroxyapatite - Mechanisms exist to both initiate and inhibit calcification

Bone formation

Osteoblast synthesize and secrete type I collagen Collagen molecules form fibrils Fibrils stagger and overlap themselves Mineral deposition Fibers join to form the framework

Bone remodeling process Constant process Proceeds in cycles - first resorption than bone formationThe calcium content of bone turns over with a half-time of 1-5 years

Bone remodeling Sequential processes of resorption and formation

3 phase process of bone remodeling(coordination of resorption and formation)

Phase I Signal from osteoblasts Precursor stimulation to become osteoclasts Process takes 10 days

Phase II Osteoclast resorb bone creating a cavity Macrophages clean up

Phase III New bone laid down by osteoblasts Takes 3 months

Bone Diseases & Treatments

Osteoporosis

CartilageVery resilient connective tissueCovers the articular surfaces of jointsSupports large airways, nose, ears etcAlso embryonic precursor of bone during embryonic developmentPrimarily glycosoaminoglycans with few fibers and very few cells

CartilageECM of collagen II crosslinked by collagen IXLots of glycosoaminoglycans and hyaluronan - Organized in megacomplexes - Hydration increases pressure resilienceCells chondrocytes- Synthesize ECM- Limited turnover abilities

JOINTSClassification of Joints FibrousCartilaginousSynovial

Joint Injuries Inflammatory and Degenerative Conditions - Arthritis - Osteoarthritis (OA) - Rheumatoid Arthritis(RA) - Gout

Gout Gout is caused by excessive uric acid level in the blood and tissue. This problem can be cause by overproduction of purine nucleotides or a decreased ability to excrete uric acid.

Purine nucleotides:IMPAMPGMP

Muscle TissueMuscle tissue functionsMovementPostureJoint stabilizationHeat generation(11.5a)

Muscle tissue typesSkeletalStriated, voluntaryCardiacHeart, striated, involuntarySmoothNonstriated, involuntaryTable 10.2

Muscle tissue terminologyFiber skeletal, cardiac & smooth muscle cellMyofilamentsActin thin filamentsMyosin thick filamentsSarcolemma plasma membraneSarcoplasm cytoplasm

Skeletal muscle(40% of Body weight)Composition:75% water

20% protein (myosin, actin, tropomyosin, myoglobin

5% inorganic salts, high energy phosphates, urea, lactic acid, minerals (Ca, Mg, P), enzymes, pigments, ions of Na, K,Cl, and amino acids and carbohydrates.

Striations: Alternating light and dark bands.

Summary: skeletal muscle fibersmusclefasciclefibermyofibrilMyofilaments :actin & myosin

T tubulesInvaginations of sarcolemmaRuns between myofibrilsConducts electrical impulses from sarcolemmaExcites SR to release Ca++ (10.8)

Sarcoplasmic reticulumSR surrounds each myofibrilStores Ca++Release Ca++ for contractionCa++ uptake for relaxation

Motor UnitDefinition: a motor neuron and all the muscle fibers it innervates.When a motor neuron fires, all muscle fibers in the motor unit contract.All or none principleA motor unit may contain hundreds to four muscle fibers (average ~ 150)Each muscle fibers receives one NMJ(14.6)

Muscle contractionAP to axon terminalACh releasedAChR activatedMuscle excitedExcitation travels down t-tubuleSR releases Ca++Ca++ activates sliding filament processMuscle contracts http://www.blackwellpublishing.com/matthews/myosin.html(14.5b)

Cross-Bridge Formation in Muscle Contraction

Energy for Muscle ContractionATP is required for muscle contractionMyosin ATPase breaks down ATP as fiber contractsSources of ATPPhosphocreatine (PC)GlycolysisOxidative phosphorylation

Sources of ATP for Muscle Contraction

Muscle Diseases & Associated Therapy

Fibromyalgia- pain in muscles and connective tissuesMuscular Dystrophy - an inherited disorder characterized by progressive proximal muscle weakness with destruction of muscle fibers and replacement with connective tissue

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