Integrative Physiology Ch. 6 - Communication, Integration, and Homeostasis
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| How many cells compose the human body? | show 🗑
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| Two basic types of physiological signals | show 🗑
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| show | Changes in a cell’s membrane potential
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| show | Molecules secreted by cells into the ECF
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| show | Chemical
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| show | Targets for short, are the cells that receive the electrical or chemical signals
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| Four basic methods of cell-to-cell communication: | show 🗑
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| Four basic methods of cell-to-cell communication: gap junctions | show 🗑
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| Four basic methods of cell-to-cell communication: contact-dependent signals | show 🗑
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| Four basic methods of cell-to-cell communication: local communication | show 🗑
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| Four basic methods of cell-to-cell communication: long-distance communication | show 🗑
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| show | A gap junction forms from the union of membrane-spanning proteins called connexins, on two adjacent cells
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| Connexon | show 🗑
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| Syncytium | show 🗑
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| What kind of molecules flow through connexons when they’re open? | show 🗑
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| The only means by which electrical signals can pass directly from cell to cell | show 🗑
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| Are all gap junctions the same? | show 🗑
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| show | In the immune system and during growth and development, such as when nerve cells send out long extensions that must grow from the central axis of the body to the distal ends of the limbs
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| show | “Cell adhesion molecules”. They act as receptors in cell-to-cell signaling. CAMs are linked to the cytoskeleton and to intracellular enzymes. CAMs transfer signals in both directions across cell membranes
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| show | Paracrine and autocrine
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| Paracrine signal | show 🗑
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| Autocrine signal | show 🗑
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| show | …diffusing through the interstitial fluid. Distance is a limiting factor for diffusion so the effective range of paracrine signals is restricted to adjacent cells
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| show | Histamine is a paracrine molecule that is released from damaged cells. It diffuses into nearby capillaries making them more permeable to white blood cells and antibodies in the plasma. They also cause fluid to accumulate and swell
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| show | All of them
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| Most long-distance communication between cells is the responsibility of… | show 🗑
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| show | …hormones
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| Hormones | show 🗑
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| show | It uses a combination of chemical and electrical signals to communicate over long distances. An electrical signal travels along a neuron until it reaches the end of the cell where it’s translated into a chemical signal.
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| show | Neurocrines
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| show | A neurocrine molecule that diffuses from the neuron across a narrow extracellular space to a target cell and has a rapid effect
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| Neuromodulator | show 🗑
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| Neurohormone | show 🗑
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| show | …their distinctions to be blurred so that the two systems are a continuum rather than two different entities
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| Cytokines | show 🗑
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| show | Cell development, cell differentiation, and the immune response
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| show | Cytokines act on a broader spectrum of target cells. Also they’re not produced by specialized cells the way hormones are (all nucleated cells can produce cytokines in response to stimuli), and they are made on demand
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| show | They’re made in advance and stored in the endocrine cell until needed
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| show | Proteins to which signal molecules (paracrine, autocrine, or hormones) bind
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| Rule about receptors | show 🗑
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| Ligand | show 🗑
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| show | First messenger because it brings information to its target cell
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| How is the receptor activated? | show 🗑
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| show | It in turn activates one or more intracellular signal molecules
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| What do the activated intracellular signal molecules do? | show 🗑
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| show | Signal molecules –(binds to)-> Receptor protein –(activates)-> Intracellular signal molecules –(alters)-> Target proteins –(create)-> Response
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| Chemical signals fall into two broad categories based on their lipid solubility: | show 🗑
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| Where can target-cell receptors be found? | show 🗑
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| Lipophilic signal molecules | show 🗑
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| Lipophobic signal molecules | show 🗑
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| show | Receptor-channels, receptor-enzymes, G protein-coupled receptors, integrin receptors
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| Signal transduction | show 🗑
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| First and second messengers | show 🗑
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| show | A device that converts a signal from one form into a different form; e.g. the transducer in a radio converts radio waves into sound waves. In biology, transducers convert the message of ECF ligands into ICF responses
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| Signal amplification | show 🗑
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| Amplifier enzyme | show 🗑
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| show | Ligand binds to and activates a protein or glycoprotein membrane receptor.
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| show | The activated receptor turns on its associated proteins which may be protein kinases (which transfer phosphates from ATP to proteins) or amplifier enzymes (which create ICF second messengers)
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| show | Second messengers alter the gating of channels (opening or closing them, affecting the cell’s membrane potential) then increase intracellular calcium which will bind to proteins and change their function, creating cellular response
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| show | Second messengers will also change enzyme activity, especially protein kinases or protein phosphatases
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| show | The proteins modified by the calcium bonding or phosphorylation (or dephosphorylation) control one or more of the following: metabolic enzymes, motor proteins, gene expression, and membrane transport/receptors
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| show | A signaling cascade starts when a stimulus (ligand) converts inactive molecule A (receptor) to an active form. Active A then converts inactive B to active B, which converts inactive C to active C and so on.
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| The most common amplifier enzymes | show 🗑
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| show | Ca^2+, cAMP, cGMP, IP_3, DAG
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| Receptor enzymes | show 🗑
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| show | Converts GTP to cGMP. Found in membrane cytosol. Activated by receptor-enzyme nitric oxide (NO)
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| Ligands for receptor-enzymes include… | show 🗑
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| show | A cytosolic enzyme called Janus family tyrosine kinase, abbreviated JAK kinase
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| G protein-coupled receptors | show 🗑
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| G proteins | show 🗑
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| show | (1) open an ion channel in the membrane, or (2) alter enzyme activity on the cytoplasmic side of the membrane
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| show | Amplifier enzymes
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| Two most common amplifier enzymes for G protein-coupled receptors | show 🗑
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| The types of ligands that bind to the G protein-coupled receptors | show 🗑
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| show | Converts ATP to cAMP. Found in membrane. Activated by G protein-coupled receptor.
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| show | Converts membrane phospholipids to IP3 and DAG. Found in membrane. Activated by G protein-coupled receptor
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| show | Signal molecule binds to G protein-coupled receptor, which activates the G protein.
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| show | G protein turns on adenylyl cyclase, an amplifier enzyme
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| The G protein-coupled adenylyl cyclase-cAMP system: (3) | show 🗑
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| The G protein-coupled adenylyl cyclase-cAMP system: (4) | show 🗑
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| The G protein-coupled adenylyl cyclase-cAMP system: (5) | show 🗑
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| The G protein-coupled phospholipase C system summary | show 🗑
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| show | A nonpolar diglyceride that remains in the membrane and interacts with protein kinase C (PK-C), a Ca^2+-activated enzyme on the cytoplasmic face of the cell membrane. PK-C phosphorylates cytosolic proteins for signal cascade
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| Inositol triphosphate (IP_3) | show 🗑
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| The G protein-coupled phospholipase C system: (1) | show 🗑
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| show | G protein activates PL-C, an amplifier enzyme
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| show | PL-C converts membrane phospholipids into DAG which remains in the membrane, and IP_3 which diffuses into the cytoplasm
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| show | DAG activates PK-C which phosphorylates proteins
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| The G protein-coupled phospholipase C system: (5) | show 🗑
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| Integrin receptors: ECF | show 🗑
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| Integrin receptors: ICF | show 🗑
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| What important role do integrin receptors play? | show 🗑
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| The simplest receptors are… (also, where are they found?) | show 🗑
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| How do receptor-channels work? | show 🗑
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| show | The neurotransmitter acetylcholine released by a neuron binds to the acetylcholine receptor and opens the channel, allowing Na+ to flow in, depolarizing the cell. A cascade results which leads to contraction of the muscle
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| How does calcium enter the cytosol | show 🗑
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| show | In the ER, where it is concentrated by active transport
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| show | They bind to the protein *calmodulin*, found in all cells, which then alters enzyme or transporter activity or the gating of ion channels. I.e. calmodulin alters proteins after binding to Ca^2+
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| Effects of calcium ions entering the cytoplasm: (2) | show 🗑
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| show | They bind to regulatory proteins to trigger exocytosis of secretory vesicles.
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| show | They bind directly to ion channels to alter their gating state.
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| Effects of calcium ions entering the cytoplasm: (5) | show 🗑
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| show | Soluble gases are short-acting paracrine/autocrine signal molecules that act close to where they’re produced
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| The best known gaseous signal molecules | show 🗑
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| Half-life | show 🗑
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| show | In endothelial tissues NO is produced by nitric oxide synthase (NOS): arginine + O2 –(NOS)-> NO + citrulline. The NO diffuses into target cells where, through a cascade, ultimately relaxes blood vessels.
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| NO in the brain | show 🗑
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| Carbon monoxide (CO) as a signal | show 🗑
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| show | Acts in the cardiovascular system to relax blood vessels. Garlic is a major source of sulfur-containing precursors which explains why eating garlic may be protective to the heart
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| show | Receptors with no known ligand
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| show | Lipid-derived paracrine signals. They are all derived from arachidonic acid, a 20-carbon fatty acid. They ultimately act on their target’s G protein-coupled receptors
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| The synthesis process network that produces arachidonic acid is known as the… | show 🗑
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| Arachidonic acid cascade | show 🗑
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| The two major eicosanoid paracrines (derived from arachidonic acid). Also, what happens to them after they’re produced? | show 🗑
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| Leukotrienes | show 🗑
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| Prostanoids | show 🗑
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| Brief description of how NSAIDs (e.g. aspirin/ibuprofen) work | show 🗑
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| show | Sphingolipids, which are extracellular signals that regulate inflammation, cell adhesion/migration, and cell growth/death. Like eicosanoids they combine with G protein-coupled receptors in their target’s membranes
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| For most signal molecules, the target cell response is determined by… | show 🗑
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| show | …the same receptor’s binding site. This can result in competition
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| Example of specificity and competition with binding site receptors | show 🗑
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| show | Either the ligand activates the receptor and elicits a response, or the ligand occupies the binding site and prevents the receptor from responding.
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| Agonists | show 🗑
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| show | Ligands that prevent (block) receptors from responding
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| Note: what does “endogenous” mean? | show 🗑
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| Example of a pharmacologically synthesized agonist | show 🗑
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| show | When epinephrine binds to the alpha receptor, e.g. in the intestinal tract blood vessels, the blood vessels constrict. When epinephrine binds to the beta-2 receptor, e.g. in skeletal muscle blood vessels, blood vessels dilate
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| What happens when a signal molecule is present in the body in abnormally high concentrations for a sustained period of time? | show 🗑
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| show | A decrease in receptor number. The cell can physically remove receptors from the membrane through endocytosis
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| Desensitization | show 🗑
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| show | …the concentration of the signal molecule
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| show | A condition in which the response to a given dose decreases despite continuous exposure to the drug; it occurs due to down-regulation and desensitization
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| show | The insertion of more receptors into the membrane. E.g. if a neuron is damaged and can’t release normal amounts of neurotransmitter, the target cell may up-regulate its receptors
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| show | By pumping the calcium back into the ER or into the ECF
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| show | One way is by degrading the ligands with enzymes in the ECF. Another is by transporting the messengers into neighboring cells
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| show | By endocytosis of the receptor-ligand complex. Once in the cytoplasm the ligands are removed and the receptors return to the membrane via exocytosis
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| show | Whooping cough: the toxin blocks inhibition of adenylate cyclase (i.e., keeps it active)
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| show | Physiological control system; regulated variables
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| show | (1) an input signal, (2) a controller to respond to input signals, and (3) an output signal
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| The input signal of the physiological control system | show 🗑
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| Physiological control system’s controller | show 🗑
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| Physiological control system’s output | show 🗑
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| show | (1) the nervous system preserves the “fitness” of the internal environment; (2) some systems of the body are under tonic control; (3) some systems of the body are under antagonistic control, (4) one signal can have varied effects
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| Cannon’s postulates describing regulated variables and control systems: (1) | show 🗑
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| Cannon’s postulates describing regulated variables and control systems: (2) | show 🗑
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| show | There are agents in the body that are constantly moderated sending opposing signals to them, e.g. parasympathetic and sympathetic pathways
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| show | As we already learned, one signal can have different effects on different receptors
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| show | A relatively isolated change occurs in the vicinity of a cell or tissue and evokes a paracrine or autocrine response
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| Reflex control pathways | show 🗑
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| show | The nervous and endocrine systems. Cytokines are also involved
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| A reflex pathway can be broken down into two parts: | show 🗑
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| show | Input signal (stimulus/sensor -> afferent pathway), integration of the signal (integrating signal), and output signal (efferent pathway -> effector -> response).
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| Stimulus/sensor -> afferent pathway | show 🗑
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| show | Evaluates the incoming signal, compares it with the *setpoint* (desired value) and decides on an appropriate response.
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| show | The output signal, or efferent pathway, is initiated by the integrating center. This is the electrical or chemical signal that’s sent to the effector (AKA target). The effector carries out the appropriate response to normalize the situation
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| Sensory receptors vs. receptor molecules | show 🗑
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| Central receptors | show 🗑
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| Peripheral receptors | show 🗑
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| Threshold | show 🗑
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| show | No they’re not associated with the nervous system so they don’t use sensory receptors to initiate their pathways
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| In endocrine reflexes, what’s the integrating center? | show 🗑
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| show | Central nervous system (brain/spinal cord)
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| Two levels of response for any reflex control pathway | show 🗑
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| Factors that influence an individual’s setpoint for a given variable | show 🗑
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| Acclimatization | show 🗑
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| show | The adaptation of physiological processes to a given set of environmental conditions if it is induced artificially in a laboratory setting
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| Feedback loop | show 🗑
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| show | Negative (keeps system near setpoint); positive
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| show | …the sensitivity of the system. If not very sensitive, the regulated variable will oscillate around the setpoint. Some sensors in physiological systems are more sensitive than others
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| Positive feedback loop | show 🗑
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| show | Hormonal control of uterine contractions during childbirth. The baby drops and puts pressure on cervix. Oxytocin is released causing uterus to contract, putting more pressure on cervix causing oxytocin release
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| Feedforward control | show 🗑
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| Example of feedforward control | show 🗑
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| Circadian rhythm | show 🗑
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| Are cortisol concentrations in the body constant? | show 🗑
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| show | Neuroendocrine reflexes
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| Specificity of reflex pathways: neural vs. endocrine | show 🗑
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| Speed of reflex pathways: neural vs. endocrine | show 🗑
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| REVIEW AND MEMORIZE DIAGRAM ON PAGE 207 | show 🗑
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| show | Neural control is of much shorter duration than endocrine control. The neurotransmitter is rapidly removed from the target after the response. Endocrine, while slower to start, lasts much longer and are ongoing
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| show | Signal strength of a neuron is constant. Thus to express intensity, the frequency of the signaling through the neuron increases. In the endocrine system, the intensity is reflected by the amount of hormone released
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| Knee-jerk response | show 🗑
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| show | REVIEW AND MEMORIZE TABLE ON PAGE 209
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| 4 basic modes of cell-cell communication | show 🗑
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| show | Gap junctions, through which ions flow to regulate contraction
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| Contact-dependent signals | show 🗑
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| Two types of local communication | show 🗑
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| show | About 100 microns is the limit
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| show | …the endocrine and nervous systems
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| Concentration gradient on which hormones travel when secreted | show 🗑
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| Nervous communication does not require… | show 🗑
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| show | Molecules that are secreted by neurons across a small gap to the target cells neurotransmitters are made in relatively LOW quantities
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| show | Large: it’s more of a brute force method of communication than neural communication
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| Endocrine vs. exocrine | show 🗑
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| How do lipophilic and lipophobic correspond to hydrophobic and hydrophilic? | show 🗑
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| cAMP is a… | show 🗑
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| show | Activated receptor bind to G-protein (a trimer) causing it to released GDP. GTP then binds to G protein, altering its conformation and causing it to detach from receptor. The altered G protein now binds with the effector (adenylyl cyclase)
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| show | GTP is hydrolyzed to GDP; the G protein then reassociates with the remainder of the dissociated G protein (beta and gamma)
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| Recap: parts of the G-protein | show 🗑
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| G protein may work in a different pathway, not cAMP but… | show 🗑
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| show | …epinephrine
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| Major adrenergic receptors. What type of receptor are they? | show 🗑
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| How do adrenergic receptors lead to vasoconstriction (thus increasing blood pressure)? Use an alpha-1-adrenergic receptor an example. | show 🗑
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| show | …mimic epinephrine. It looks enough like the hormone to be able to bind to the receptor. Example: pseudophed, which constricts blood vessels in the nasal cavity leading to nasal decongestion
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| show | On smooth muscle cells
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| Most receptors on the heart are what type of receptor? | show 🗑
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| show | The body releases a ton of catecholamines in an attempt to recover from the injury. This is chronic and results in a down-regulation of beta-adrenergic receptors on the heart
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| show | G protein-couple receptor kinase
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| Give detailed explanation of the process of down-regulation | show 🗑
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| show | The decision is whether to degrade the receptor or send it back out to the surface. It depends on how long the agonist (ligand) is there and how high the concentration is. If it’s chronic, the sorting endosome will degrade the receptor
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| Chronic beta-blocker therapy results in… | show 🗑
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| Where is blood pressure changes sensed in the body? How does this play a role in homeostasis | show 🗑
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| show | An outside factor is required to shut it off
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| show | E.g. for ovulation, wherein you want a powerful surge of response
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