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Functions of all tissues is
Maintenance of a constant internal environment
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Intracellular fluid<->Intersticial fluid<->Plasma<->Organs<->External Environment
Exchange and communication are key concepts for understanding physiological homeostasis
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Homeostasis refers to the dynamic mechanisms that
Sense or detect deviations in physiological variables from their "set point" values bu initiating effector responses that restore the variables to the optimal range
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Exploring Homeostasis
- Identify the internal environmental variable
- Establish the "set point' value for that variable
- Identify the inputs and outputs affecting the variable
- Examine the balance between the inputs and outputs
- Determine how the body monitors/senses the variable
- Identify Effectors that restore variable to its set point
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How are homeostatic systems controlled?
Reflex pathways
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Negative feedback
An increase in a parameter causes changes that lead to a decreases in the value of the parameter, vice versa.
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Positive feedback
An increase in a parameter that causes changes that lead to a further increase in the value of the parameter, vice versa.
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Homeostatic control systems require:
Communication, networks utilizing signal molecules that bind to receptors
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Communication Signals
Neural: signal crosses synapse to affect target cells
Endocrine: signal reaches distant targets via blood transport
Paracrine: signal reaches neighboring cells via ISF
Autocrine: signal affects the cell that synthesized the signal
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Physiological Parameters
Internal environment variable that is regulated so it remains within a "set point"
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Circadian rhythms add an aticipatory component to homeostasis
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Total body balance depends on:
net gain vs net loss
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Metabolism:
Catabolic breakdown: need energy sources and O2, produce CO2
Anabolic synthesis: need precursors for nucleic acids, protiens, lipids and carbs
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Multicellular organisms
Bulk transport; mvmnt of substances to/from cell surface to interface with external environment
Communication: cells communicate in order to coordinate fxns
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Allosteric modulator
forms non-covalent bond with protein
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Covalent modulator
forms a covalent bond with the protein
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Law of mass action
increase in the amount of reactants will increase the rate of production formation
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Glycolysis: oxidation of glucose
- Net: 2 molecules of ATP synthesized 2 NAD+
- Can occur anaerobically to form lactic acid
- Not much energy captured
- Oxidized NAD+ is regenerated
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Citric acid and electron transport chain
- carries electrons to the ETC where they are transferred to O2 reducing it to H2O
- Synthesizes ATP by capturing energy
- Lots of energy captured
- Acetate to 2CO2
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ATP provides energy to make a molecule more reactive
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Glycolysis
- Aerobic conditions:
- Glucose to pyruvate
- Small ATP generated
- NAD+ reduced to NADH
- Anaerobic conditions
- Glucose to lactate
- NAD+ regenerated to maintain ATP production
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Diffusion due to random thermal motion
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Net flux
accounts for solute movements in both directions
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Net movement
toward the area of lesser concentration until dynamic equilibrium is reached
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Factors that affect diffusion
- Magnitude of concentration gradient
- Permeability of membrane
- presence of transport or pore proteins
- Surface area
- Molecular mass
- Distance
- biological membranes tend to be thin
- Temperature
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Hypertonic, Isotonic, Hypotonic
- Hypertonic, cell shrinks, solution more concentrated
- Hypotonic, cell swells, solution more dilute
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Protein ion channels
- transmembrane proteins that form aqueous pores
- carry ions through lipid membranes down their electrochemical gradient
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Carrier-mediated transport
- transmembrane protiens
- transport ions and other solutes down or against their gradients
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Active transport
solute moved against its concentration gradient
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ATP hydrolysis changes protein conformation
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Secondary active transport
- solute is glucose, amino acid, or another ion
- binding changes protein conformation and affinity for solute
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Secondary active transport
Symport
Antiport
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primary active transport ATPases
•H+ ATPase found on inner mitochondrial membrane –involved in ATP synthesis
- •H+ / K+ ATPase
- found in stomach and kidney
- •Ca2+ ATPase:
- –Found in plasma membrane, where
it pumps Ca2+ out of the cytosol into the ECF - –Found in the membrane of smooth
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Epithelial Transport
- often asymmetrical:
- Net transport can occur in one direction across the epithelial sheet or tube
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Intracellular Signal Transduction
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- •Lipid soluble (nonpolar)
- messengers
–Cytosolic - (intracellular) receptors
- •Water soluble (polar)
- messengers
–Kinase - receptors
–G protein coupled receptors
•Cyclic nucleotides (via nucleotide cyclases)
•Cytosolic Ca2+ (via phospholipase C)
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Lipid-soluble messengers act as regulators of transcription factors
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G-protein coupled signal transduction
This is a GTPase enzyme, active when GTP is bound, inactive when GDP is bound
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Adenylate Cyclase enzyme: cyclic AMP formation and PKA activation
- PKA is activated by cAMP, relative activity of AC and PDE enzymes controls [cAMP]
- Adenylate cyclase catalyzes the formation of cAMP
- Phosphodiesterase inactivates cAMP
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One type of second-messenger enzyme can coordinate many cell processes via target protiens
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PKC is avtivated by calcium release form the ER and DAG in plasma membrane
- PLC hydrolyzes mbn lipid (PIP2) to form IP3 (water soluble) and DAG (lipid soluble)
- PKC requires both calcium and DAG for activation
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Arachidonic Acid signaling initiated by:
- Phospholipase A2-these lipids are important in paracrine signaling
- COX enzyme inhibited by ibuprofen eg.
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Antagonist: competes for a receptor with a chemical messenger normally in body
Agonist: A chemical messenger binds to receptor and triggers cells response
Down-regulation: decrease in total number of target-cell receptors for a given messenger
Up-regulation: increase in total number of target-cell receptor for a given messenger
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Electrical potentials result from:
separation of charged particles
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Charge separation across membrane is small fraction of total number of particles
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Steady state:
net ion flux due to diffusion is exactly balanced by active transport of ions by the pump NOT EQUILIBRIUM
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Nervous system: rapid control of processes in the organism (behavior)
- Composed of neurons and other cellular elements
- sensory systemsintegrative systems
- motor systems
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Anterograde transport: away from cell body: kinesin
Retrograde transport: toward cell body: dynein
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CNS Cell types
neurons
astrocytes: form blood brain barrier
oligodendrocytes: form myelin sheaths
microglia: brain macrophages
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Afferent neurons and efferent neurons are in the __________ nervous sytem. Over 99 percent of neurons are ____________.
PNS Interneurons
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Presynaptic: Sender
Postsynaptic: receiver
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Transient changes
2 types: graded potentials (transduction and integration)
action potentials (transmission)
mediates information processing and trasmission by nerve cells
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The opening and closing of ion channels results from changes in integral proteins due to:
membrane potential changes or ligand binding
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Repolarization of the action potential is due to:
Action potential is "all or none"
- rapid inactivation of depolarization-activated sodium channels
- slower activation of depolarization-activated potassium channels
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Sodium channels are located:
only at modes (active sites)
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What is lost in MS?
Myelin sheath which leads to slowing or failure of AP conduction
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B-cell receptor
Immunoglobulin on plasma membrane surface
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T-cell receptor
Immunoglobulin-like molecule on plasma membrane surface. Interacts with specific antigen only when it is "complexed with an MHC molecule
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Major Hitocompatibility Complex (MHC)
- gene cluster code for proteins found at cell surface
- Everyone has a unique set of MHC genes and proteings
- MHC serves as "self' identiy tags
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Helper T cells only interact with antigen encountered on macrophages, dendritic cells & B cells since they express Class II MHC protiens
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Acquired Immune Response
- Extracellular pathogen
- Microbe-infected cells or cancer cells
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How does your immune system lear to distinguish the bodies' own molecules form foreign ones?
During fetal and early post-natal life, T and B cells that recognize "self" molecules are eliminated in th thymus (colonal deletion) or inactivated in the periphery (colonal inactivation)
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Immune surveillance
process where body (self) recognizes itself as distinct forn foreign molecules
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Cellular Components
Neutrophils: blood-born phagocyte eat foreign matter
Monocytes: macrophage precursors in blood
Macrophages: tissue dwelling phagocytes
Dendritic cells: (macrophage-like cells)
Lyphocytes:
Mast Cells: reside in tissue; mediate allergic responses
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Cytokines
- Protein messengers released by immune cells and other tissue cells
- Function as both paracrine/autocrine and endocrine signals
- IL-1 & TNFa: initiates inflammatory response adn mediate sickness response
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Innate (nonspecific) response
- Phagocytes have receptors that recognize classes of foreign molecules
- Injury or infection cause chemotaxis- attraction of immune cells to the site
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Acquired immune response
- mediated by lymphocyte makes a receptor that recognizes a specific foreign molecule or antigen
- All of the progeny of each lymphocyte are called
clones- recognition of antigen results in
clonal expansion-proliferation of specific lymphocyteEffecor cells-carry out attackMemory cells-for future encounters with antigen
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Primary and secondary lyphoid organs
- Primary-bone marrow and thymus
- Secondary-lymph nodes, spleen, tonsils and adenoids
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Humoral (antibody-mediated) response
- B lymphocytes produce immunoglobulin molecules that recognize a specific antigen (secreted as antibodies)
- Antibody (AB) functions: attachment to antigen can directly inactivate it, attachment to antigen enhances phagocytosis (opsinization)
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