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    Homeostasis and The Cell

    Pamela R. Bosch, PT, PhD

    PT 531, Applied Human Physiology

    A.T. Still University of Health Sciences, Physical

    Therapy Program

    The copyrighted materials available in this class are for educationaluse only. One copy per student is permitted for educationalpurposes. Redistribution of copyrighted material is not permitted."

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    Lecture Objectives1. Describe the structure of a typical cell and the cell membrane.

    2. Identify the purpose of the major parts of a typical cell, the nucleus and the cytoplasm.3. Identify the purpose of the organelles of the cytoplasm, including the smooth and rough endoplasmic

    reticulum, the golgi complex, lysosomes, peroxisomes, mitochondria, vaults.

    4. Understand the purpose of the cytoskeleton found in the cytosol of the cell.

    5. Describe how the cell membrane regulates movement (transport) of substances across the membrane based

    on physical properties of the solute.

    6. State the difference between simple diffusion, facilitated diffusion and active transport, and provideexamples of each.

    7. Describe the membrane potential and why it exists.

    8. Describe the distribution of body fluids between intracellular and extracellular fluid, interstitial fluid, and

    plasma.

    9. State how the balance of fluid is determined between intra- and extracellular fluid spaces.

    10. Define osmosis and osmotic pressure. Provide a practical example of this in the human system.

    11. Explain how the relative volumes of plasma and interstitial fluids are balanced, and cite factors causing

    plasma volume to be lost to interstitial volume.

    12. Define edema and ascites.

    13. Contrast the composition of plasma, interstitial fluid, and intracellular fluid in terms of concentrations of

    sodium, potassium, chlorine ions, and protein.

    14. Describe cystic fibrosis and what causes it.

    15. Describe stem cells and their significance.

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    Homeostasis

    Defined as maintenance of arelatively stable internal

    environment

    Does not mean thatcomposition, temperature, and

    other characteristics are

    absolutely unchanging

    Homeostasis is essential forsurvival and function of all cells

    Each cell contributes tomaintenance of a relatively stable

    internal environment

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    Homeostasis

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    Homeostasis

    Body cells are contained in watery internalenvironment through which life-sustaining

    exchanges are made

    Extracellular fluid (ECF)Fluid environment in which the cells live (fluid

    outside the cells)

    Two componentsPlasma, interstitial fluid

    Intracellular fluid (ICF)Fluid contained within all body cells

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    Homeostasis

    Factors homeostatically regulated include

    Concentration of nutrient molecules Concentration of O2 and CO2 Concentration of waste products pH Concentration of water, salt, and other

    electrolytes

    Fluid volume and pressure Temperature

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    Disruptions in Homeostasis

    Can lead to illness and death Pathophysiology

    Abnormal functioning of the bodyassociated with disease

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    Cells & Tissues!

    > 200 types of cells! 4 primary!tissue types:!

    Nervous !Epithelial !Muscle !Connective !

    Blood is !also a tissue!

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    Nervous Tissue!

    Voltage-sensitive channels! Integrate incoming signals! Conduct signals rapidly to target organs! Connect complex networks! Initiate, integrate and transmit signals!

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    Epithelial Tissue!

    Lines cavities and free surfaces of body!

    Membranes with protein pumps & receptors! Microvilli increase surface area! Endothelium is a type of epithelium that lines

    circulatory system!

    Glands are specialized epithelial tissue withexocrine or endocrine function!

    Serves as boundary with selective permeability!

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    3 types: skeletal, cardiac, smooth! Sarcoplasmic reticulum for calcium storage & release! Contractile proteins & regulatory proteins! Sarcomeres (in cardiac & skeletal muscle)! Function: force generation!

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    Tendons, cartilage, ligaments, bone, blood! Connects and supports various parts of the body! Blood transports materials throughout the body!

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    Typical Cell

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    Nucleus!

    Contains cells geneticmaterial, DNA , which:!

    Directs proteinsynthesis!

    Is the genetic blueprintduring cell replication!

    Contains theNucleolus, which:! contains RNA !

    Translates &transcribes geneticcode!

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    Cytoplasm

    Portion of cell interior not occupied by thenucleus

    Consists of bothOrganelles

    little organsDistinct, highly organized, membrane-enclosed

    structures

    Cytosol Complex, gel-like mass in which the cytoskeleton is

    found

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    Cellular Organelles!

    Endoplasmic reticulum! Golgi complex! Lysosomes! Peroxisomes! Mitochondria!

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    Endoplasmic Reticulum!

    Smooth ER synthesizes lipids forsteroid hormone synthesis ! Packages and dischargesboth

    proteins and lipids! ER increases as needed!

    EX: in the liver for dischargingdetoxifying enzymes to break downdrugs or foreign compounds!

    Rough ER synthesizes proteins!and lipids! Called rough because it has

    ribosomes that synthesizeproteinsand lipids! Proteins may be secreted from the cell

    as hormones or enzymes! Proteins and Lipids may be

    transported within the cell for cellmaintenance!

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    Golgi Complex!

    Collects proteins synthesized

    in ER and packages them

    into vesicles that aredelivered to different sites:!

    intracellular sites! May replace missing

    segments of membrane!

    May be incorporated intoother organelles (like

    lysosomes)!! !!

    Released from the cell by

    exocytosis!

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    2 functions of transit through the Golgi stack:"1. Modification of raw proteins into final form"2. Sorting proteins by function and destination"

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    Lysosomes!

    Contain hydrolytic enzymes thatdestroy cellular bacteria engulfedin vesicles by pinocytosis orphagocytosis!

    Participate in apoptosis(programmed cell death)!

    Material unable to be digested bylysosomes remains as residual

    bodies ! Example: asbestos fibers remain in the

    lungs once inhaled!

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    Tay-Sachs Disease:! a lysosomal enzyme deficiency that

    allows gangliosides to accumulate!Gangliosides are molecules found in nerve

    cell membranes; important in cell to cell

    communication !

    Tay-Sachs disease causes progressiveneurodegeneration and death by theage of 4!

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    Peroxisomes

    Membranous sacs that houseoxidative enzymes that detoxifyvarious waste products!

    Oxidative enzymes use oxygen toremove hydrogen from toxicmolecules, producing

    hydrogen peroxide! Catalase breaks hydrogen peroxide into water and oxygen, which are harmless to the cell!

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    Mitochondria!

    Extract energy from

    nutrients, and viathe Krebs Cycle &

    Electron TransportSystem, transform

    energy into a

    useable form for

    cellular activities!

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    Mitochondria!

    Site of most ATP production! Contains citric acid (Krebs cycle) enzymes! Mitochondrial DNA codes for severalmitochondrial enzymes needed for aerobic

    metabolism!

    Mitochondrial DNA mutates easily!

    Thought to be partially responsible for manyneurodegenerative diseases (PD, HD, ALS), SIDS,and cardiomyopathy!

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    Cytoskeleton

    Complex protein network of cytosol that actsas bone and muscle of cell

    Three distinct elementsMicrotubules: transport of other components within cells

    Microfilaments: actin, solid fibersIntermediate filaments: structuralstability in cell

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    Element Function

    Microtubules Transport secretory vesiclesMovement of specialized cellprojections

    Form mitotic spindle during cell divisionMicrofilaments Contractile systems

    Mechanical stiffenersIntermediatefilaments

    Help resist mechanical stress

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    Plasma Membrane Structure

    Fluid phospholipid bilayer embedded with proteins Also has small amount of carbohydrates

    On outer surface onlyCholesterol

    Contributes to fluidity and stability of cell membrane

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    Plasma Membrane Structure

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    CYSTIC FIBROSIS!

    Membrane proteins form channels across the lipid bilayer!Channels are selective for specific particles (Na+, K+, forexample)!In CF, a gene mutation impedes or prevents formation ofchloride channels (called CFTR, cystic fibrosis

    transmembrane regulator ) in epithelial cell membranes !

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    CYSTIC FIBROSIS!

    CFTR is made in the endoplasmic reticulum of epithelial cells, !in CF, CFTR is degraded due to a lack of a necessary aminoacid. !

    CFTR never gets packaged and sent out of the ER to thecell membrane to form channels!No CFTR means that Cl- cannot be transported across epithelialcells!Cl- moves with Na+ (NaCl), so Na+ transport is also decreased!

    Reduced Na+ movement decreases water movement, resultingin thicker mucus in airways!

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    Membrane Transport

    Unassisted membrane transport (passive)Diffusion Osmosis (refers to diffusion of water)

    Assisted membrane transportCarrier-mediated transport

    Facilitated transportActive transport

    Vesicular transport

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    Membrane Transport

    Cell membrane is selectively permeable Properties of particles influence whether theycan permeate cell membrane without

    assistance, such as:

    Relative solubility of particle in lipidSize of the particlepolarity (charge) of the particle

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    Diffusion & Osmosis!

    Diffusion: passive movement of molecules fromhigh to low concentration!

    Osmosis: passive movement of water (across amembrane) down its concentration gradient (that

    is, from high concentration to low concentration)!

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    Membrane Transport

    DiffusionUnassisted membrane transportUniform spreading out of molecules due to theirrandom intermingling

    Molecules move from area of high concentrationto area of low transport

    Process is crucial to survival of every cellPlays important role in

    Exchange of oxygen and carbon dioxide between blood andair in lungs

    Movement of substances across kidney tubules

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    Membrane Transport

    Diffusion

    Particles (solutes) and solvents (water) will naturally

    disperse to spread evenly if they can"

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    Membrane Transport

    Factors affecting rate of diffusion collectively

    make up Ficks law of diffusion:

    Magnitude (or steepness) of the concentrationgradient

    Permeability of the membrane to the substance Surface area of the membrane across which diffusion

    is taking place

    Molecular weight of the substance Distance through which diffusion takes place

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    Ficks Law of Diffusion

    Q (rate of diffusion) = C P A MW X

    C = concentration gradient P = permeability A = surface area MW = molecular weight of the substance X = distance traveled

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    Membrane Transport

    Osmosis Net diffusion of water down its

    own concentration

    gradient

    Water doesnt want to be crowded! Thus, it will move from

    where there is more water to where there is less water!"

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    Osmotic Pressure and

    Hydrostatic Pressure

    The net movement of water increases pressure onthe side the water moves to

    Pressure builds until equilibrium is reached This pressure is hydrostatic pressure

    The weight of water pushing against a surface Osmotic pressure a measure of the tendency for

    osmotic flow of water

    Results from differences in relative concentrations ofsolutes and water in cell and ECF

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    Fluid dynamics at the capillary!

    CHP = capillary hydrostatic pressure!

    COP = capillary osmotic pressure!

    IFHP = interstitial fluid hydrostatic pressure!

    IFOP = interstitial fluid osmotic pressure!

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    Fluid Exchange!

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    Edema

    The presence ofexcess fluid in the

    body tissues!Usually, theexcess fluid is inthe extracellularcompartments!

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    Intracellular EdemaSwelling of cells!

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    Extracellular Edema!

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    Extracellular Edema

    Increased capillary pressureRetention of salt and water in kidney failureHigh venous pressure, as with heart failure,

    venous obstruction (pregnancy), or failure of

    venous pumps

    Decreased arteriolar resistance

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    Extracellular Edema!

    Increased Capillary Permeability!

    Immune response!Toxins!Bacterial infections!Burns!

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    Extracellular edema from decreased plasma proteins

    (causes decreased colloid osmotic pressure)!

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    Extracellular Edema

    Chronic lymphatic obstruction cancer radiation therapy radical mastectomy

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    Extracellular

    Edema!

    Chronic lymphedema fromradical mastectomy!

    Lymphedema from

    filarial nematode

    infection of thelymph system!

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    Assisted Membrane TransportCarrier Mediated, and includes

    Facilitated Diffusion and ActiveTransport!

    A mechanism for transporting large, polar, poorly solublesubstances across membrane!A means of transporting some small ions across themembrane!

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    Assisted Membrane Transport

    Accomplished by membrane carrier flipping itsshape

    Can be active (active transport) or passive(facilitated diffusion)Characteristics that determine the kind and

    amount of material that can be transferred

    across the membraneSpecificitySaturationCompetition

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    Facilitated diffusion Substances move from a

    higher concentration to a

    lower concentration

    Requires carrier moleculeBut no energy required!

    Means by which glucoseis transported into cells

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    Carrier Mediated

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    Active Transport

    Moves a substance against its concentrationgradient

    Requires a carrier molecule Primary active transport

    Requires direct use of ATP Secondary active transport

    Driven by an ion concentration gradientestablished by a primary active transport system

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    A good example of active transport is the sodium-potassium

    pump! It transports sodium (3) from inside to outside thecell; while transporting 2 potassium ions from outside to

    inside!!

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    Membrane Potential

    Plasma membrane of all living cells hasa membrane potential (polarized

    electrically)

    Separation of opposite charges acrossplasma membrane

    Due to differences in concentration andpermeability of key ions

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    Na+"Na+"

    K+"K+"

    - - - - - - - - - - -

    +++++++++++

    -70 to -90 mV!

    Typical Cell at Rest!

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    Membrane Potential

    Nerve and muscle cellsExcitable cells can do work!Have ability to produce rapid, transientchanges in their membrane potential when

    excited

    Resting membrane potentialConstant membrane potential present in cells

    of nonexcitable tissues and those of excitable

    tissues when they are at rest

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    Ion Concentration

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    Resting Potential

    Proteins!

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    Membrane Potential

    Effect of sodium-potassium pump onmaintaining membrane potential

    Makes only a small direct contribution tomembrane potential (20%) through its

    unequal transport of positive ions (3 Na+

    out/2 K+ in)

    This is a good example of active transport,which requires energy (ATP)!

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    Hyperkalemia

    Abnormal elevation of K+ in bloodNormal ranges: 3.5 5 mEq/LCauses:Kidney dysfunction

    Adrenal Gland dysfunctionMedications (ACE inhibitors, NSAIDs)

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    Hyperkalemia

    Destruction of the concentration gradientfor K+ across muscle cell membranes

    interferes with muscle contraction, and ifexcessive (> 7 mEq/L) is associated with:

    ArrhythmiasCardiac arrest

    Death

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    Iontophoresis

    A modality used in PT Promotes healing Works because charged particles move

    down an electrical gradient

    Medication is driven into the skin with astimulator carrying a low electrical current

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    Stem Cells

    Undifferentiated cells that can become almostany type of cell.

    Two types:Embryonic stem cells (ESC): from early divisions

    of fertilized eggs; totipotent

    Tissue-specific stem cells: generate specialized celltypes of specific tissues; pluripotent

    For more information, go to:http://stemcells.nih.gov/info/basics/

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