Cell Biology and Physiology I
Cell Biology and Physiology I PSL 534
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Merle Waelchi MD
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Date Created: 09/19/15
PSL 534 Cell Biology and Physiology Overview PSL 534 Cell Biology and Physiology I continues next semester as PSL 535 Cell Biology and Physiology ll Together PSL 534 and 535 are intended to help you learn the most important and most medically relevant vocabulary and concepts in cell biology and physiology More specifically you will learn basic vocabulary and concepts regarding structure function and signaling in cells tissues organs and organ systems In a traditional medical school curriculum the study of cell structure histology was separated from the study of cell function cell physiology Also biochemistry the study of the structure and reactions of biomolecules was treated as a separate discipline However these distinctions make no sense in light of our current appreciation of the inseparability of cell structure and cell function and the fact that cell structure and function are direct consequences of the structure and reactions of the molecules that comprise the cells Therefore in the Cell Biology and Physiology courses we seek to help you integrate the previously artificially separated disciplines of physiology histology and biochemistry The sections of PSL534 include Fundamentals Connective tissue including cartilagebone Blood amp Hematopoiesis Transport Epithelium Signaling amp nerve Muscle Autonomic Signaling Cardiovascular DETAILED OBJECTIVES 01 Fundamental Concepts T 1 Define histology physiology biochemistry cell biology function dysfunction dyspnea heart failure pulmonary edema cardiomyopathy uremia paradigm prognosis diagnosis differential diagnosis enzyme Define holism and give its etymology Describe how cell biology and physiology relate to medical holism List the various interacting organ systems that comprise the body List the various levels of structuralfunctional organization in the body Relate these levels of organization to the biopsychosocial model Explain why it is counterproductive to try to think about structure separately from function in diagnosing or treating illness Name the organ systems whose actions and interactions underlie body function Name in order the levels of suborganization within each organ system Describe the mechanistic paradigm also known as the biomedical or physiological paradigm Define and illustrate the concept of causality Discuss the role of temporality in causality Explain why a mechanistic view of body function can always be depicted as a causeandeffect sequence of chemical and physical changes 09 07 9159 444 N4039 13 Describe the process of differential diagnosis and explain the relationship between differential diagnosis and the assumption of causality 14 Explain how you would detect the presence of feedback in a correctly depicted causeandeffect sequence of bodily functions 15 Define and distinguish between positive feedback and negative feedback in a causeandeffect sequence of bodily functions 16 Explain the relationship between negative feedback and compensation Explain the relationship between positive feedback and decompensation 17 Explain why compensation regulation and homeostasis are such closely related concepts 18 Define teleology and contrast the teleological and mechanistic views of body function 19 Explain why biomedical scientists reject teleology as an adequate explanation of cause 20 Explain why teleology is not always a reliable guide to diagnosis and treatment in medicine 21 Cite some of the strengths and some of the limitations of the mechanistic view of body function 22 Discuss what biomedical science can or cannot tell us about the spiritual or metaphysical aspects of human existence 23 Given a description of some body function or response categorize the description as either teleological or mechanistic and explain why 24 Describe the potential roles of positive and negative feedback in a biochemical reaction sequence State which type of feedback would yield relative stability in the concentration of a reaction endproduct 02 Fundamental Concepts II T A Concept of quotInside and Outsidequot 1 State the role of epithelial cells as an important body boundary layer 2 Explain why from a physiologist39s point of view the contents of the gastrointestinal tract are considered to be on the outside of the body 3 Define invagination 4 Explain why a physiologist would consider the air in the lung39s alveoli to be on the outside of the body 5 Describe what it means to say that the alveolar epithelial cell layer is continuous with the cutaneous epithelium Describe what it means to say that the gastrointestinal epithelial cell layer is continuous with the cutaneous epithelium 6 Define what physiologists mean when they refer to the body39s external environment Define what physiologists mean when they refer to the body39s internal environment Identify the type of cell layer that generally separates the external from the internal environments 7 Define and distinguish between intracellular fluid and extracellular fluid and state 2 names for the biological structure that separates the body39s intracellular and extracellular compartments 8 Define cytosol 9 Define and distinguish between interstitial fluid plasma lymph and transcellularfluid State how these four fluid types are related to extracellular fluid 10 State the relationship between interstitial fluid and the body39s internal environment Distinguish between intracellular fluid and the body39s internal environment 11 Explain why the chemical composition of interstitial fluid is so critical to the normal functioning of the body39s cells 12 List the major constituents of interstitial fluid 13 Compare and contrast using qualitative terms the composition of interstitial fluid with the composition of the intracellular fluid in a typical skeletal muscle cell 14 Describe the barrier that confines blood within the cardiovascular system 15 Explain why it is false to say that blood is an extracellular fluid 16 List the major constituents of normal blood and distinguish between those that are cellular and those that are noncellular extracellular 17 State the primary functions of leukocytes 18 Contrast the relative numbers of leukocytes and erythrocytes in normal blood A NN AO MN N A00 N NNNN OOVGU39I 0000M A0 4000 JON Awwwww OLDOO IGU39I 9159quot l em 9 Describe the origin and characteristics of platelets thrombocytes and state their major function in blood State the location and two primary roles of hemoglobin Describe the steps involved in getting 02 from alveolar air into the blood and bound to hemoglobin Write a chemical reaction for the reversible binding of 02 to Hb List in order the fluid spaces and boundary layers that an 02 molecule would have to traverse to move from its binding site on a hemoglobin molecule to the site within a skeletal muscle cell where oxidative metabolism takes place Define hematocrit and give typical values for men and women Explain how hematocrit is determined in the clinic and state why hematocrit is sometimes called packed cell volume State which components of blood can easily cross the vascular endothelium and which cannot State why plasma proteins and blood cells cannot easily cross the vascular endothelium Compare and contrast the composition of plasma and interstitial fluid Explain why whole blood is red but plasma is pale yellow and interstitial fluid is generally clear nearly colorless Explain how fluid gets into the lymph system Explain why lymph and interstitial fluid are essentially identical in composition List the 4 fluid compartments whose volume you would have to sum up to calculate precisely the body39s extracellular fluid volume Define total body water in terms of intracellular fluid volume and extracellular fluid volume State the approximate fractions of the total body water that are found in the intracellular and extracellular spaces State the approximate fractions of the extracellular fluid volume that are found in the interstitial and plasma spaces Why are lymph and transcellular fluid volumes usually overlooked in making this approximation Define transcellular fluid and list several sites in the body where it is found Describe how a clinical laboratory would obtain a sample of blood plasma Describe how a clinical laboratory would obtain a sample of blood serum Compare and contrast blood serum and blood plasma Given the plasma volume and hematocrit calculate blood volume Calculate estimates for your total body water intracellularfluid volume extracellular fluid volume and plasma volume Concept of quotMass and Energy quot Define concentration and be able to solve concentrationamountvolume problems ie be able to solve for any one of these three given the other two Define and be able to convert between the units of concentration common in medicine gL mgmL molarity and percent Readily convert between metric units particularly kilo deci centi milli micro and nano Be able to convert between cm and inches and also between pounds and kg Describe the steps by which an unknown volume can be measured by the indicatordilution technique and list the assumptions that underlie this technique Given data from an indicatordilution procedure calculate an unknown volume and list the assumptions implicit in this calculation 03 Fundamental Concepts Iquot T Nfgt P Concept of quotScalequot Have an intuitive sense of meter centimeter millimeter and micrometer micron State in metric units and compare the approximate sizes ofthe body typical body cells proteins and small molecules State the difference between a logarithmic and an arithmetic scale Define resolution resolving power as it pertains to the eye or other visual instruments 5 State the approximate limit of resolution of the unaided eye the light microscope and the transmission electron microscope TEM or EM for short 6 State distinguish between the major factors that limit the resolution of the unaided eye the light microscope and the EM 7 Compare and contrast the biological structures that can be seen with the unaided eye light microscope and EM 8 Define magnification scale factor and be able to solve problems involving magnificationsize of object in imagesize of object in nature ie be able to solve for any one of these three given the other two 9 Be able to use a calibration bar known distance on a picture or drawing to determine the actual size in nature of objects shown in the picture or drawing 10 Be able to use a calibration bar known distance on a picture or drawing to determine the magnification of the picture or drawing 11 List several biological or biochemical processes that take place over the time scale ofjust a few milliseconds 12 List several physical or chemical processes that take place overthe time scale ofjust a few nanoseconds 13 Define speed velocity and be able to solve problems involving velocitydistancetime ie be able to solve for any one of these three given the other two 14 Explain why movement seems to be quotspeeded upquot when viewed under a microscope B Concept of quotSignalingquot 1 Explain why the normal functioning of most biological mechanisms involves and depends on signaling 2 Define signaling pathway 3 List four elements processes involved in a biological signaling pathway 4 Given a particular signaling pathway identify the parts of the pathway where each of the four elements processes is taking place 5 Define hormone and give a synonym L01 LAB T 1 Define field of view and know how this varies with the objective used to examine tissue 2 Understand what is meant by fixation embedding and staining of tissue 3 Define eosinophilic and basophilic and know the cellular structures generally stained by each in HampE 4 Know the types of molecules or structures which are lost or unstained in typical HampE preparations 5 Know the range in size for objects which can be viewed in the light microscope 6 Be able to find layers in organs or other major functional divisions by staining patterns and cell density 7 Be able to deduce the simple underlying 3D shape from a 2D section 804 Cell Organization Lipid Structure and Membrane Properties T 1 Distinguish the techniques of light microscopy electron microscopy and freezefracture 2 Categorize and distinguish the common histological stains and the structures revealed by their reactions 3 Draw the general structure and apply the system of nomenclature for the saturated and unsaturated fatty acids and triacylglycerols 4 Draw the general structure and apply the nomenclature of the phospholipids sphingolipids glycolipids and cholesterol 5 Identify the polar and nonpolar portions of membrane lipids 6 Describe the general composition and diagram the structural features of biological membranes 7 Describe how amphipathic molecules assemble into lipid bilayers via noncovalent interactions 8 Distinguish integral versus peripheral proteins 9 Illustrate that membranes are fluid structures 10 Distinguish the structures of the phosphorylated derivatives of phosphatidylinositol and describe their significance 11 Distinguish the specificity of the phospholipases 805 Cell Organization Subcellular Compartments and the Flow of Information T 1 Recognize and interpret morphological structures and staining patterns color of cells and subcellular structures 2 List and identify the biochemical activity and physiological function of the organelles of a cell 3 Describe and illustrate the notion of traffic between intracellular compartments separated by membrane barriers a signal and receptormediated targeting to the destination i nucleusnuclear envelope nuclear pores nuclear localization signal importins ii ERsignal sequence signal recoginition particle ER retention signal iii lysosomesignal sequence to enter lumen of the ER sorting in the trans Golgi network mannose 6phosphate and its receptorfortargeting to the lysosome b movement from one compartment to another via vesicular fusion i Coatomers and SNAREs 4 Distinguish the features of exocytosis and endocytosis a exocytosis b phagocytosis c pinocytosis d receptormediated endocytosis 5 Identify and distinguish the cytoskeletal filaments a microfilaments and its subunit actin independent of cell type b intermediate filaments and their subunits cell type specific c microtubules and its subunit tubulin 6 Distinguish the modes of celltocell signaling a secreted signaling molecules versus direct cellcell contact b autocrine paracrine and neurotransmission endocrine and juxtacrine c hydrophilic versus hydrophobic signaling molecules d the six receptormediated signal transduction pathways 7 Identify the importance of cell anchoragecell contact L02 CYTOLOGY LAB T For the following topics 1 Nucleus 2 Cell undergoing mitotic cell division 3 The nucleus and its structural features in EM sections 4 Cytoplasmic organelles 5 Cytoplasmic staining 1 Be able to identify the organelles described above those with specific examples in EM and in LM where possible 2 Be able to relate the ultrastructure of the cell to its function understand the implications of variations in the size or number of cell organelles and possible secretory transcription or active transport activities Understand the relationship between cytoplasmic staining and cytoplasmic contents Know the difference in resolution preparation and staining of LM and EM sections Identify plasma membranes and understand their structure Understand which components are electron dense in the electron micrograph 6 Understand and identify the structure of the nucleus nuclear membrane nuclear pore 39 39 quot 39 quot and 39 39 in LM where possible and EM 9159quot 0607 Embryology and Stem Cells T 1 Describe the development of the ectoderm endoderm and mesoderm define embryonic germ layeL 2 Understand the correlation between the embryonic germ layers and the 4 adult tissue types 3 Define inner and outer cell mass morula blastocyst and bilaminar disc embryoblast and trophoblast epiblast and hypoblast know the developmental period in which these arise 4 Understand the difference between totipotent and pluripotent and the developmental stages when these are present 5 Describe the events of gastrulation in terms of induction cell migration and changes in cell adhesion know the significance of the primitive streak and the notochord as induction zones Understand how changes in potential cell growth adhesion apoptosis and gradients established by induction zones can affect development 7 Define the embryonic mesenchyme cell 8 Know the origin of the neural crest and neural tube 9 Define stem cell and transit amplifying cells and understand the significance of stem cells for repair and replacement 10 Distinguish between adult and embryonic stem cells in terms of origin and potential 11 Define niche and understand its significance in repair 12 Know the stem cell source forthe tissues discussed epidermis intestinal gland amp blood As you learn about more tissues in the coming weeks you will also learn about the stem cells which exist and the cell derivations In this way you will be able to understand the links between cell types that differ greatly in morphology and function yet share a common antecedent 13 Compare embryonic development to adult repair in terms of the role of signaling molecules and cell adhesion Know the specific action of Wnt and notch 14 Understand the process of obtaining embryonic stem cells 9 08 Connective Tissue T 1 Extracellular matrix a List the cellular and noncellular components of connective tissue b Categorize and compare the three major classes of molecules constituting the extracellular matrix 2 Structural features of collagen polypeptide a Describe the primary structure and the special features of glycine lysine and proline residues b Describe the secondary structure and report the lack of typical tertiary structure c Diagram the quaternary structure in terms of a triple helix and rationalize in terms of the forces stabilizing such a helix d Identify hydroxylation and glycosylation as examples of posttranslational modification of proteins particularly of collagen e Identify proteolytic cleavage as another example of posttranslational modification and illustrate its effect on collagen f Identify colvalent crosslinking as still another example of posttranslational modification and illustrate its effect on collagen g Categorize the basis of genetically inherited collagen disorders and predict their consequences h Identify the basis of acquired collagen defects in ascorbate deficiency 3 Glycosaminoglycans GAGs a Recognize the structure and nomenclature of the GAG molecules and identify their common characteristics repeating structures of disaccharides with negative charges b Sketch and distinguish GAGs versus proteoglycans and proteoglycan molecule versus proteoglycan aggregate Identify their components c Rationalize the physical properties of the proteoglycans in relation to their structure d Describe how an adhesive glycoprotein eg fibronectin can link a cell to its extracellular matrIx 4 Elastic fibers a List the two major components of elastic fibers b List the 3 most common forms of elastic fiber in tissues 5 Cell function a Chart the flow of information for the synthesis of collagen by a fibroblast 09 Connective Tissue 02 Cellular Components T 1 Distinguish connective proper and specialized connective tissues a distinguish in histological section the type of connective tissue b relate the predominant fiber type the density of fibers and the orientation of fibers ot the function of the tissue 2 Describe the general functions of connective tissues ad and relate these to specific structural components of the connective tissue a Structural support b Medium exchange c Defense d Fat storage 3 Describe the functions of individual types of connective tissue cells a Fixed connective tissue cells fibroblasts adipocytes mesothelial cells and pericytes b Transient connective tissue cells plasmacells mast cells and macrophages 4 Distinguish the various cell types in histological stains L03 Connective Tissue Lab T 1 Identify connective tissue and specify the type of connective tissue This is an important part of analyzing the structure and function not only of connective tissue itself but the organs in which connective tissue provides support Identify the different types of extracellularfibers in connective tissue and the different stains described 2 Understand the relationship between the function of these tissues and their structure in terms of fiber type density and orientation and cellular constituents 3 Identify and understand the structure and function of the various cell types of connective tissue 4 Identify the ground substance and understand its composition and function 5 Know the special stains used for the different fibers types of connective tissue 6 Include as part of your basic medical vocabulary the following terms a Stroma b Lamina propria 1011 Connective Tissue 0304 Cartilage and Bone T 1 Compare cartilage and bone with respect to GAGs extracellular fibers appositional and interstitial growth source of nutrition for osteocytes and chondrocytes 2 Know the differences between hyaline cartilage elastic cartilage and fibrocartilage in terms of fiber types and location in the body 3 Understand the biomechanical properties of cartilage understand the importance of fluid and fluid movement and extracellular fiber type and orientation on cartilage biomechanics 4 Know the relationship between osteon orientation bone remodeling and external load in bone 5 Be able to describe the relationship between osteoblasts macrophage or stromal cell and osteoclast role of RANK RANKL OPG PTH calcitonin and BMP 6 Define intramembranous and endochondral bone formation and understand how these relate to mesenchyme hyaline cartilage epiphyseal plate Which bones are formed by intramembranous means 7 Understand the effects of disuse on both cartilage and bone How does this relate to Wolff s Law What region of bone is particularly prone to bone loss 8 Identify the features in the osteon which relate to communication between osteocytes blood vessels communication between osteons 9 Define the terms osteoid woven bone mature bone cancellous bone trabecular bone compact bone epiphysis diaphysis medullary cavity 7 10 Understand the difference between the organic and inorganic components of bone matrix and the effects of vitamin C vitamin D and Calcium on bone matrix 11 Understand how changes in the following processes would affect bone formation or resorption Differentiation of osteoblasts Synthesis of osteoid by osteoblasts Mineralization of osteoid Differentiation of osteoclasts Bone resorption by osteoclasts Cartilage and Bone Lab T 1 Be able to distinguish the different types of cartilage from bone and from all of the types of connective tissue studied so far 2 Identify in microscopic section the 3 types of cartilage and understand their difference in structure and normal function 3 Define the terms listed in the introduction 4 Identify compact bone cancellous bone and medullary cavity in gross specimens microscopic images and radiographic images and identify the components of the Haversian system in LM sections 5 Identify the cells of cartilage and bone and understand the ultrastructural differences between bone and cartilage cells 6 Relate the cells in bone to the function and control of BMU 7 Understand the difference between endochondral and intramembranous bone formation and recognize these in section Relate these features to the gross specimens and radiographic Images 8 Identify the components of the synovial joint in section and in radiographic images 812 Blood 01 Blood Cells and Hemopoiesis T 1 Describe the terms a Formed elements b Plasma c Serum d Buffy coat e Hematocrit f Clot 2 List the principal types of cells in blood and provide their function 3 Describe the functions of the bone marrow and distinguish red versus yellow marrow 4 Distinguish the properties of pluripotential hemopoietic stem cell progenitor cell precursor cell 5 Catalog the myeloid versus the lymphoid lineage CFUGEMM versus CFUL of hemopoietic cells 6 Distinguish by histological stains the various cell types in the erythropoietic series 7 Describe the roles of colony stimulating factors erythropoietin thrombopoietin and interleukins 8 Describe the contents of platelets and their functions 9 Describe the red blood cell a Morphology and elastic properties b Housekeeping versus erythroidspecific functions S13 Blood 02 Iron Metabolsim T 1 Identify the major steps in iron absorption transport storage use and excretion including a The form of Fe participating in these steps b The factors affecting the efficiency of these steps c The proteins mediating these steps 2 Explain the role of IronResponsive Element IRE in regulating the levels of transferring receptor anf of ferritin and predict the consequences on transferrin receptor ferritin and iron uptaketransport 3 List the general methods for assaying body iron stores 4 Describe the basis for and consequences of hypochromic anemia hemochromatosis and sideroblastic anemia S14 Blood 03 Heme Metabolsim T 1 Identify glycine and succinylCoA as the precursors of heme 2 Identify porphobilinogens as intermediates in heme synthesis 3 Identify the enzyme catalyzing the committed step of heme synthesis 4 Identify the enzyme that is the principal target of lead inhibition 5 Describe the basis for the porphyrias and predict consequences of lesions early versus late in the pathway 6 List the names of intermediates and endproducts of heme degradation 7 Identify reactants and enzyme required for bilirubin conjugation and describe the biological role of conjugation 8 Identify the names of excreted compounds derived from the catabolism of bilirubin 9 Distinguish between the direct and indirect van den Bergh tests of serum bilirubin in terms of methodology compounds which react and clinical significance 10 Identify the bases forjaundice and how prehepatic and posthepatic types can be distinguished S15 Blood 04 Red Blood Cell Metabolism T 1 Examine the roles of pathways of RBC energy metabolism in maintaining the integrity of the cell a Identify the roles of superoxide dismutase glutathione peroxidase and glutathione reductase as they relate to MetHb b Identify the major reactions producing NADPH and the major reactions using NADPH in the red blood cell c Identify the biochemical events in RBC associated with glucose 6phosphate dehydrogenase deficiency and predict its consequences 2 Identify the role of pyruvate kinase in ATP production in RBC and how enzyme deficiency can lead to hemolysis 3 Compare the distinguishing features of the two major categories of hemoglobinopathies 4 Identify the nature of the basic defect in the thalassemias and define d and Bthalassemia 5 Describe and explain the molecular basis of sickle cell anemia and identify the factors which may contribute to sickle cell crisis 6 Identify the basis for Hemoglobin M and explain the clinical consequences 7 lnterpret the data contained in the Complete Blood Count CBC report a RBC hematocrit HCT hemoglobin HGB and reticulocyte Retic b WBC and the various cell types constituting the leukocyte population c Platelets S16 Blood 05 Hemostasis T 1 Identify the four phases of hemostasis including the processes and components of platelet activation 2 Describe the key reactions of the blood coagulation pathway what starts the intrinsic versus the extrinsic pathways where do they converge what factors are nonenzymatic and the Components of the Final Common Pathway 3 Select the common theme of the enzymatic cascades involved in coagulation 4 Describe the basis of the thrombincatalyzed fibrinogen to fibrin conversion why fibrin aggregates and identify how covalent crosslinks are formed 5 Describe the components involved in clot dissolution 6 Identify the molecular basis of hemophilias 7 Explain the requirement for vitamin K in blood clotting and how dicoumarol works as an anticoagulant 8 Categorize the regulation of clotting activity including the actions of thrombomodulin protein C serine proteinase inhibitors antithrombin Ill and heparin L05 Blood And Hemopoiesis Lab T 1 Be able to identify the terms given in the preparation section 2 Be able to identify the formed elements of blood and know the normal frequency of each cell type in blood 3 Be able to distinguish the following cell classes Developmental stages from mature stages for erythrocytes and granulocytes Erythropoiesis series from the granulopoiesis series 4 Be able to place developing series in their correct sequence Understand how this sequence relates to the stages of hemoglobin production in erythrocytes or to the synthesis of specific granules in granulocytes 5 Understand the structure of bone marrow and know the normal location of active marrow in adults Understand the role of bone marrow in hemopoiesis formation of connective tissue stem cells and osteoclast differentiation ldentify megakaryocytes 6 Be able to identify lymphocytes neutrophils eosinophils and plasma cells in connective tissue S17 Transmembrane Transport T 1 State the two preconditions that must exist before movement flow will occur 2 Write a general equation relating flow driving force and conductance 3 Given any two factors in this equation be able to calculate the third 4 Write specific forms of this equation for bulk flow of fluid through a tube diffusional flow of a substance 5 List the major factors determining fluid conductance of a tube diffusional conductance 6 State the name by which the equation in 2 is known when it is applied to the flow of electricity State the name by which the equation in 2 is known when it is applied to simple diffusion 7 Write an equation relating resistance to conductance 8 Distinguish between the physical form that electric current usually takes in electronic devices and the physical form that electric current usually takes in physiological processes 9 Define a Hydrostatic pressure b Perfusion pressure c Chronic obstructive pulmonary disease COPD d Pulmonary edema 10 Describe the properties of a membrane that influence diffusional conductance 11 Describe the properties of a solute that influence diffusional conductance 12 Explain why the solubility of a solute in the membrane influences diffusional conductance 13 Write an equation for Fick39s Law of Diffusion and explain the significance of each of its factors 14 Define and illustrate Osmolarity lsosmotic Hyperosmotic Hypoosmotic lsotonic Hypertonic Hypotonic 15 Given the chemical composition of a solution determine its osmolarity whether it is isosmotic hyperosmotic or hypoosmotic compared to normal cells and whether it is isotonic hypertonic or hypotonic compared to normal cells 16 State the two driving forces that influence the movement of water across membranes 17 Explain why only impermeant solutes create a lasting osmotic effect across a semipermeable membrane 18 List the essential conditions to have osmosis 19 Define osmotic pressure 20 Write an equation for Van39t Hoff39s Law and explain the significance of each of its factors 21 Given values for the hydrostatic and osmotic pressures acting across a semipermeable membrane predict the direction of water flow masher 22 State why many cell membranes have a permeability to water that is greater than the permeability to water of a simple phospholipid bilayer 23 State the two driving forces that influence the movement of ions across membranes 24 Explain in physical terms what it means to say that there is a voltage difference across a membrane 25 Explain in physical terms what it means to say that a cell has a negative membrane potential 26 Given the concentrations of an ion inside and outside a cell calculate the membrane potential that would be needed to exactly balance the concentration force acting on the ion 27 Define electrochemical equilibrium 28 Given the concentrations of an ion inside and outside a cell and given the actual membrane potential predict the direction of the net electrochemical driving force on the ion and state which way the ion would flow if the cell membrane were permeable to it 818 Transmembrane Transport II T 1 Use information about the extracellular and intracellular concentrations of a solute together with information about the membrane potential to predict which way the solute would move y passive transport 2 Given information about the extracellular and intracellular concentrations of a solute together with information about the membrane potential and also given information about which way the solute is actually moving across the cell membrane determine whether the solute is being passively transported or actively transported State the basic difference between passive and active transport across cell membranes Compare and contrast the driving forces for passive transport of uncharged vs charged solutes Define and describe transmembrane transport via simple diffusion facilitated diffusion via channel proteins facilitated diffusion via carrier proteins and active transport via carrier proteins 6 Compare and contrast the modes of transport mentioned in 5 with regard to free energy change potential throughput selectivity and directionality 7 Compare and contrast the modes of transport mentioned in 5 with regard to saturability draw graphs to illustrate these differences 8 Describe how you could experimentally distinguish between each of the modes of transport mentioned in 5 9 In regard to a saturable transport process define Vmax and km illustrate these concepts graphically 10 State what determines the direction of net transport via a reversible transport mechanism like carrier proteins 11 Define and contrast uniport cotransporter symport and antiport exchanger give at least one specific example of each 12 Describe at least 2 transporters that help to keep intracellular Ca very very low 13 State the main mechanism responsible for keeping intracellular Na low and intracellular K high 14 Describe the mechanism of transport via the NaK ATPase 15 Describe how the NaK ATPase interacts with the NaCa antiport to keep intracellular Ca very very low 16 State the action of digitalis and describe its effect on intracellular Na K and Ca 17 Explain why digitalis may be prescribed for a patient with heart failure even though it is a deadly porson 18 Explain why cells are at risk for swelling and describe the role of the NaK ATPase in counteracting the tendency for cells to swell 19 Define endocytosis and exocytosis 20 Describe transmembrane transport by simple passive endocytosis pinocytosis What kinds of solutes can be transported across the membrane by this mechanism 21 Explain why endocytosis and exocytosis can only mediate active transport when they are linked to energyrequiring processes or reactions 9159quot 11 S19 Epithelium 1 T 1 Know the general structure of intercellularjunctions and the hemidesmosome compare the different types of intercellularjunctions with respect to the typical location on the cell function and type of cytoskeletal filament to which each attaches Be able to designate the general location of these junctions on a drawing of LM image Be able to distinguish the tight junctions from the adhesive junctions and from the hemidesmosome in an EM image 2 Review the cytoskeletal filaments and the terminal web 3 Understand the polarity of epithelial cells and know which structures are apical and which are basaL 4 Define the different types of epithelium define endothelium Be able to associate typical functions with each type of epithelium Be able to identify the type of epithelium in an LM or EM image or in a drawing 5 Known the structure and function of cilia versus microvilli know which is connected to the terminal web Be able to distinguish these in EM images 6 Understand the structure and function of basolateral folds or striations Be able to identify these on a diagram an LM image and an EM image 7 Define simple versus complex glands serous versus mucus glands serous demilunes tubular versus acinar glands Be able to distinguish glands from ducts in a drawing or LM image 8 Know the differences in morphology and secretions of serous versus mucus secreting cells Be able to distinguish serous from mucous glands in LM sections 9 Review the structure of the basal lamina the distinction between basal lamina and basement membrane 820 Epithelium 2 Transepithelial Transport T 1 Define and distinguish between External environment Internal environment Transmembrane transport Transepithelial transport Paracellular pathway Transcellular pathway Apical luminal mucosal Basal serosal quotbloodquot side Basal lateral basolateral Tight junction zona occludens Mucous membrane mucous mucus 2 Sketch a generic epithelial cell layer and label its various sides surfaces and critical features 3 Describe tightjunctions and explain their critical role in transepithelial transport specifically explain why there could not be any active transepithelial transport without tight junctions 4 Using a sketch and description explain the mechanism forthe transport of 02 across the alveolar epithelium 5 Using a sketch and description explain the mechanisms forthe absorption of glucose Na Cl and water from the small intestine Name the location where the NaK ATPase is found in most epithelial cell layers Given information about the type and distribution of various transport proteins on a particular set of epithelial cells make predictions about the resulting transport functions of that epithelium 8 Create sketches to show the distribution of critical transport proteins on particular epithelial cells and use the sketch to make predictions about the resulting transport functions of that epithelium 9 Using a sketch as in 2 explain the mechanisms for absorption of amino acids from the small intestine quot39393quot quot39 D 510 575 lp 10 Explain why the absorption of Na from the small intestine can build up a voltage difference across the intestinal epithelium Explain why this voltage difference would eventually inhibit the absorption of Na if anions such as Cl were not reabsorbed along with the Na 11 State the name and location of the epithelial cells in the stomach that secrete HCl Given a sketch showing the location of the relevant transport proteins on these cells explain the mechanism for HCl secretion 12 Describe the function ofthe striated duct cells of the salivary gland Given a sketch showing the location of the relevant transport proteins on these cells explain the mechanism for their secretion 13 State the name and location of the epithelial cells in the sweat glands that are responsible for the hypotonic character of normal sweat Given a sketch showing the location of the relevant transport proteins on these cells explain the mechanism for secretion of a hypotonic sweat 14 Summarize the epidemiology main symptoms natural history and etiology of cystic fibrosis 15 State the meaning of CFTR and describe its relationship to cystic fibrosis 16 Explain how a defect in CFTR can account forthe main dysfunctions seen in the pancreas sweat glands and lungs of victims of cystic fibrosis L06 Epithelium Lab T 1 Be able to distinguish epithelial tissue from any other type of tissue 2 Be able to classify the type of epithelium and identify the apical and basal margin of individual epithelial cells and of the tissue as a whole Understand the general function of each type of epithelium 3 Identify in LM and EM cilia and microvilli and know the difference in structure and function Identify basolateral folds relate these to striated duct cells and understand the function 4 Identify in EM the different types of intercellular and cellularto basal lamina junctions and know the structure and function of each type 5 Identify the secretory specializations of epithelial cells serous vs mucous secretory cells vs ducts acini vs tubular glands Understand the relationship between the location of the secretory products within the cell apical or basal and the space into which the products will be discharged 6 Identify and understand the structure of the basement membrane Review 821 Signaling and nerve 01 T 1 Be able to describe the physical space of the synapse including the somatic neuromuscular junction be able to relate the structure to the chemical and electrical events described in the following lectures Know the function of glia at the synapse 2 Understand the difference between chemical and electrical synapses 3 Know the differences between antero and retrograde transport the two MAPs involved and the mechanisms of transport 4 Know the capacity of neurons for repair regeneration in CNS and PNS and the role played by Schwann cells and oligodendrocytes in either aiding or inhibiting this 5 Know the functions and types of glia in central and peripheral nervous system 6 Understand function of dendritic spines know the difference between pseudounipolar multipolar neurons 7 Understand the morphology of axons axon hillock initial segment myelin sheath nodes of Ranvier Be able to identify these in LM or EM sections where possible depending on the resolution Describe the components of a somatic sensory autonomic and enteric ganglion or plexus Be able to identify dorsal root or autonomic ganglion cells and their associated satellite glia 9 Understand the structure of peripheral nerves the organization amp composition of the investing sheaths and the organization of the blood supply Be able to identify these in LM and EM section 26 9 22 Signaling and nerve 02 T N4 P Uquot 9 599 44 4o 4 N 4444 DUIbu 4 N NNAA N AO QOO N at Define and distinguish between intercellular and intracellular Define and distinguish between the following modes of intercellular chemical signaling a Juxtacrine b Autocrine c Paracrine d Endocnne e Neurotransmitter State another name for an endocrine messenger Define a Connexin and connexon b Neuroendocrine d Second messenger Describe andor diagram the relationship between the following elements of a typical second messenger signaling pathway First messenger Receptor Gprotein Amplifier enzyme Phosphorylated precursor Second messenger Protein kinase Cellular response Explain why some intercellular signaling substances must exert their effects on target cells via activation of plasma membrane receptors whereas other signaling substances are able to penetrate the target cell membrane and access intracellular receptors directly Give examples of each kind Describe in general terms the similarities and differences between ionchannellinked receptors and Gproteinlinked receptors Describe the structure and function of the nicotinic cholinergic receptor Define protein kinase describe the general mechanism by which protein kinases become phosphorylated and the general consequences of that phosphorylation State the general characteristics of Gproteins and explain why they are called Gproteins Describe the general mechanism by which Gproteins are activated and the general consequences of that activation Describe the specific conditions that must exist in order for the Gs protein to activate adenylate cyclase Describe how the synthesis and degradation of cAMP is controlled State in general terms the main actions of cAMP Predict in general terms the consequences of administering a phosphodiesterase inhibitor Explain how different types of cells can use the same second messenger system eg Gs adenylate cyclase cAMP protein kinase A to effect such divergent responses State the specific subtypes of adrenergic and cholinergic receptors found on cardiac pacemaker cells List important similarities and differences between Gs and Gi proteins Describe the Gq 77 lP3DAG 77 CacalmodulinCkinase cell signaling pathway List several examples of the role of Ca as an intracellular signaling chemical State the approximate range of cytosolic concentrations over which Ca functions as an effective signaling molecule List 5 mechanisms used by cells to keep the cytosolic concentration of free ionic Ca below a toxic level Which of these are normally the most important State the type of Gprotein linked to each of the following receptors 01 02 31 and 32 adrenergic and M2 and M3 muscarinic cholinergic 390 7w 510 UN 23 Signaling and nerve 03 Membrane Potentials T 1 Define membrane potential resting membrane potential depolarization and hyperpolarization 2 Explain why opening more K channels in a cell membrane causes the membrane potential to move toward the K equilibrium potential 3 Explain why opening more Na channels in a cell membrane causes the membrane potential to move toward the Na equilibrium potential 4 Explain the role played by each of the following in establishing and maintaining the resting membrane potential NaK ATPase Nongated K channels K quotleakquot channels Transmembrane Na transporters eg NaCa antiport or Na glucose symport 5 Explain what specific changes in a K channel a Na channel or a Ca channel would cause a cell at rest to rapidly depolarize 6 State the immediate and longterm effects on membrane potential of inhibiting the NaK ATPase compare the relative magnitude of these two effects and account for their difference in magnitude 7 Explain why an epithelial cell might have a different membrane potential across its apical membrane than across its basolateral membrane 8 Contrast the magnitudes of membrane conductances permeabilities to Na and K in a normal resting neuron 9 Using axes of membrane potential vs time sketch a graph showing a the normal resting membrane potential b the effects of brief graded subthreshold depolarizations and c the effect of a brief suprathreshold depolarization for a neuron or skeletal muscle cell 10 Distinguish between an excitable cell and a nonexcitable cell 11 Describe the quotall or nothingquot characteristic of action potentials 12 Describe in general terms what causes the channel changes that lead to depolarization in a Sensory nerve endings b Interneurons within the CNS c Motor neurons d Skeletal muscle cells 13 Describe the basic components and features of the flexion reflex nociceptive reflex 14 List at least 4 sites within a normal flexion reflex quotarcquot where depolarization leads to formation of an action potential 15 Define a Synapse b Neuroeffectorjunction c Neurotransmitter d Excitatory postsynaptic potential epsp e End plate potential 824 Signaling and nerve 04 Action Potentials T 1 Using axes of membrane potential vs time sketch graphs showing the normal resting membrane potential and an action potential for a neuron a skeletal muscle cell and a cardiac muscle cells 2 State the major similarities and differences between neurons skeletal muscle and cardiac muscle in regard to resting membrane potentials and action potentials 3 Name the various phases of a normal neural action potential 4 Explain the role played by each of the following in the various phases of a normal neural action potential a NaK ATPase b K quotleakquot channels c Voltagegated quotfastquot Na channels d Voltagegated quotdelayed rectifierquot K channels e Other transmembrane Na transporters eg NaCa antiport 5 Explain the nicknames quotfastquot and quotdelayed rectifierquot as they are applied to certain Na and K channels 6 Describe and name 3 states for the voltagegated Na channel and 2 states for the voltagegated K channel 7 Contrast the magnitudes of membrane conductances permeabilities to Na and K in a normal resting neuron 8 Sketch graphs to show the progression of changes in Na conductance and K conductance during an action potential in a normal neuron 9 Interpret the progression of changes in Na conductance and K conductance during an action potential in a normal neuron in terms of the quotstatesquot of voltagegated Na and K channels 10 Define and illustrate the concept of refractory period and explain the relationship between refractory period and Na channel inactivation 11 Explain the functional importance of refractory period 12 Explain why a typical neuron can still produce hundreds or even thousands of action potentials even after inhibition of the NaK ATPase 13 Explain how local anesthetics blockthe formation of action potentials in neurons 14 Name 2 or 3 common local anesthetics describe the source and biological action of tetrodotoxin 15 Explain why an action potential is said to be propagated rather than conducted 16 Describe local ionic currents and explain their role in propagation of an action potential 17 Describe how the propagation of an action potential is affected by refractory period axon diameter and myelination of axons 18 State approximate velocities of conduction of action potentials in large myelinated axons in small unmyelinated axons L07 Nervous System Lab T 1 Identify peripheral nerve ganglion white and grey matter in section and distinguish neural from other types of tissues Know the different locations of soma for somatic and autonomic sensory and motor neurons 2 Distinguish neurons axons myelin and glial cells within neural tissue 3 Be able to relate the structure of myelinated and unmyelinated axons in light and EM section to the function of conducting action potentials understand the relationship between axon diameter and conduction velocity of action potentials 4 Identify the following components of synapses pre and post synaptic terminals synaptic cleft synaptic vesicles in synapses between neurons and in neuromuscularjunction Relate these structures to the events of synaptic transmission 5 Identify the neuromuscularjunction in light and electron microscopic section 6 Identify astrocytes in section 825 Signaling and nerve 05 Neurotransmitters and Synaptic Function T 1 Describe in detail the sequence of events in a normal flexion reflex beginning with a nociceptive stimulus and ending with contraction of flexor muscles 2 Describe the normal point of origin of action potentials in sensory afferent neurons in motor efferent neurons and in interneurons 3 Define and distinguish between motor efferent neuron interneuron and peripheral sensory afferent neuron on the basis of function anatomical location and basic morphology particularly the relationship of axon to soma 4 Describe the following parts of a motor neuron and state the function of each dendrites cell body soma axon hillock initial segment axon and axon terminals 5 Describe the typical locations for ligandgated vs voltagegated ion channels on motor neurons and describe in detail how these channels participate in the initiation and propagation of an action potential and in the release of neurotransmitter from the axon terminals Define synapse synaptic cleft and synaptic transmission Explain why it is incorrect to say that synapses transmit action potentials from one neuron to another 4 A 4 01500 N AO N444 A OLOOOV 0 MN NA NNN 01500 NNN COMO N O 0000 A0 000000 00 00 V0701 A 00 00 00 A00 OLD Describe the general mechanisms involved in the synthesis storage and release of neurotransmitter from an axon terminal Describe the general mechanism by which a neurotransmitter exerts an effect on the postsynaptic cell and describe the general mechanisms for terminating that effect Define and describe the mechanisms responsible for EPSP39s and lPSP39s Define temporal summation and explain its role in initiating an action potential in a postsynaptic cell Define spatial summation and explain its role in initiating an action potential in a postsynaptic cell Compare and contrast synapses and neuroeffector junctions Define neuromuscularjunction also called myoneural junction List and distinguish between the effector target tissues innervated by somatic vs autonomic motor neurons Distinguish between small molecule neurotransmitters and polypeptide neurotransmitters neuropeptides Name two subcategories of small molecule neurotransmitters and give examples of each Name the subcategory of neurotransmitters to which ACh DA NE and Epi belong List important examples of cholinergic neurons Distinguish between preganglionic and postganglionic autonomic motor neurons and explain why there is no such thing as a postganglionic somatic motor neuron Name the neurotransmitter utilized throughout the parasympathetic nervous system Name the usual neurotransmitter of postganglionic sympathetic neurons and cite one important exception to this rule Describe the mechanisms for synthesis storage and release of ACh Describe the mechanisms for degradation and recycling of ACh from the synaptic cleft Define acetylcholinesterase inhibitor and describe the mechanisms and effects of its action Also give at least one example of such a drug Explain why acute exposure to an acetylcholinesterase inhibitor can be fatal Define ligand agonist and antagonist and explain why an antagonist is often called a quotblockerquot Define and distinguish between nicotinic and muscarinic cholinergic receptors on the basis of their agonists antagonists and locations in the body Describe the location structure and function of nicotinic cholinergic receptors of the muscle sub type Nmuscle receptors Describe the functional anatomy of the somatic neuroeffectorjunction myoneural junction List a detailed causeandeffect sequence to show how an action potential in a somatic motor neuron leads to an action potential in the skeletal muscle fiber that it innervates State similarities and differences between a somatic neuroeffectorjunction and an excitatory nervenerve synapse in terms of structure and function Describe the synthesis name each intermediary storage and release of catecholamine neurotransmitters You do not need to memorize the chemical structures of the intermediaries nor do you need to remember the names of each enzyme in the synthetic pathway Explain why among the neurons that synthesize catecholamine neurotransmitters some release dopamine some norepinephrine and some epinephrine State the location and main function of chromaffin cells Define and describe the composition of quotadrenalinequot Describe the mechanisms for degradation and recycling of catecholamines from the synaptic cleft and also from the blood stream Define catecholamine reuptake inhibitor and describe the mechanisms and effects of its action Also give at least one example of such a drug Explain why acute exposure to cocaine can be fatal Define adrenergic receptors also called adrenoceptors and state where you would be likely to find them in the body 41 Describe how one might distinguish between a and 3 adrenergic receptors on the basis of their selective agonists and antagonists You do not need to memorize the names of specific exogenous adrenergic agonists or antagonists 42 Explain why we think that there are distinct subtypes of d and 3 receptors name these subtypes 43 Define dopaminergic receptor describe how you could experimentally distinguish between a dopaminergic receptor and an adrenergic receptor 44 Describe the mechanism of action and effects of curare explain why curare and atropine would not have the same effects on the body 45 Explain why some neuropeptides are described as being quotmodulatorsquot rather than classic neurotransmitters 46 Explain why some neuropeptides are described as being quotcolocalizedquot and quotcoreleasedquot along with other neurotransmitters 47 Name the type or family of neuropeptides that enkephalins and endorphins belong to and name the general type of receptor that they activate 26 Skeletal Muscle 01 T 1 Understand the composition of the epi peri and endomysium and the relationships between these connective tissue investments and the large blood vessels capillaries and muscle fibers and proprioceptors 2 Understand the ultrastructural relationship between Ttubules SR and myofibrils and between the SR and the myofibrils 3 Know the functional components of the sarcomere thin and thick filaments Z disk and M line A band and l band be able to relate these elements to the sliding filament mechanism of contraction Know the primary anchoring proteins desmin dystrophin titin and their position within the myofibril or myofiber 4 Know the embryonic origin of skeletal muscle and the difference between myotube and myofiber 5 Understand the capacity of muscle fiber for repair hypertrophy and regeneration understand the role of satellite cells and the trophic effects of innervation Understand the effects of stretch lGF1 and myostatin on myofiber hypertrophy Know the changes that occur with aging 6 Know the general composition location and innervation of muscle proprioceptors 7 Define the motor unit 8 Know the difference between parallel and pennate muscle architecture and the structure of the musculotendinous junction 27 Skeletal Muscle 02 T 1 Describe the role of Ca in regulating cross bridge formation 2 Describe the cross bridge cycle in terms of ATP binding hydrolysis and release of products Ca regulation and movement in the heads of myosin explain the difference between normal rest and rigor 3 Know the mechanism for reuptake of Ca into the SR the binding proteins in the SR understand the significance of interfering with either calcium release or calcium reuptake on muscle contraction 4 Describe the coupling of action potential at the ttubule to the conformation change in channel proteins in the SR Define electromyogram know the underlying casues of fibrillations versus fasciculations Explain the difference between endplate potential and action potential in the muscle fiber Understand how agents that block release receptor binding or AChE activity will affect muscle contraction 8 Be able to compare the time course of the muscle action potential with the time course of calcium increase and decrease within the cytosol After the next lectures you should also be able to compare these to the time course of force development during a contraction N939quot 9 Understand the difference between the endplate potential and the myofiber action potential Know what kind of ion channels are involved in each Know the location of the endplate potentials and action potentials S28 Skeletal Muscle 03 T 1 2 3 Uquot 6 Be able to distinguish isometric concentric and eccentric contractions Understand the lengthtension relationship of isometric contractions distinguish between active and passive components of force and know the molecular basis for passive and active force Understand the relationship between moment arm and torque and the optimal joint angle for most muscles Understand the time course of the force developed during isometric contractions the correlation between myosin ATPase rates and contraction time compare the duration of the action potential Calcium levels with the duration of the twitch contraction some of these issues are introduced in the next lecture Describe the forcevelocity relationship of isotonic contractions relate the maximum velocity to actinmyosin ATPase Define the regions of isometric and eccentric contraction on the force velocity curve Relate the architecture of muscle to differences in shortening velocity maximal force production and maximal length change during contraction Understand the relationship between the power of muscle and the velocity of shortening and the mechanical disadvantage of muscles at joints S29 Skeletal Muscle 04 T 1 2 3 4 5 6 7 8 9 Define the three types of muscle fibers Relate fiber types I Ilb Ila to the relative use of aerobic versus anaerobic metabolism Relate the fiber types to the type of myosin ATPase cross bridge cycling rate Relate the metabolic needs of the three types of muscle fibers to their ultrastructure mitochondria intracellular glycogen capillary beds in the perimysium fiber diameter Know the relative power not the particular numbers of each of the three main pathways for generating ATP Describe the mechanism of temporal summation relate temporal summation to the release and reuptake of Ca to the duration of action potentials in the muscle and to the elastic properties of the muscle and tendon Define motor units by their mechanical metabolic and ultrastructural properties Explain the role of motor unit recruitment in producing smooth gradations in force of contraction Describe spatial summation in terms of motor unit recruitment 10 Understand the impact of neurogenic versus myogenic disorders on motor unit recruitment S30 Cardiac Muscle Histology And Physiology T INSTRUCTIONAL OBJECTIVES are questions from the coursepack L08 Skeletal Smooth and Cardiac Muscle Lab T 1 2 9 N33591 Be able to answer the questions already given in this lab manual Be able to identify skeletal and smooth muscle and distinguish these from the other tissue types which we have studied so far Correlate the ultrastructure of skeletal muscle with the sliding filament theory of contraction excitation contraction coupling and the energy requirements of contraction Define the various connective tissue layers of skeletal muscle Identify muscle spindles Correlate the smooth muscle ultrastructure with its function Be able to compare skeletal smooth and cardiac muscle make a chart with respect to anatomy ultrastructure and physiology including phycological controls S31 Smooth Muscle Histology and Physiology T INSTRUCTIONAL OBJECTIVES are questions from the coursepack S32 Autonomic Nervous System 01 T FUNCTIONAL ORGANIZATION OF THE AUTONOMIC NERVOUS SYSTEM INSTRUCTIONAL OBJECTIVES are questions from the coursepack S33 Autonomic Nervous System 02 T AUTONOMIC NEUROEFFECTOR FUNCTION INSTRUCTIONAL OBJECTIVES are questions from the coursepack S34 Signaling 01 The Receptor as a Tyrosine Kinase Pathway T 1 Delineate in terms of structure binding properties and enzymatic activity the domains of a tyrosine kinase TK receptor 2 Explain or schematically diagram the events following the binding of hormoneligand to a TK receptor what happens and what is its purpose 3 Define the structural and binding properties of a protein containing an SH2 domain Cite at least three examples of such a protein 4 List in sequence the classification of components in the mitogenactivated protein kinase MAP kinase cascade 5 Distinguish the three branches of MAP kinase cascade in terms of the key distinctive kinase and the general type of biological response 6 Explain how phosphatidyl inositol 3 kinase PI3K binds to an activated TK receptor and how this signal transduction pathway can affect metabolic changes via its effects on protein synthesis 7 Using insulin and plateletderived growth factor as examples illustrate signal transduction from a TK receptor via the MAP kinase cascade and PI3K cascade 8 Explain how oncogenes are related to growth factorsgrowth factor receptors and provide an example to illustrate the relationship S35 Signaling 01 Hormonal Action via Guanylate Cyclase T 1 Compare and contrast the components and key features of the receptor as a guanylate cyclasequot pathway of signal transduction versus a The receptor coupled to adenylate cyclasecAMP cascade pathwayquot b The receptor as a tyrosine kinase pathwayquot 2 Identify the source targets and effects of atrial natriuretic factor 3 Describe the domains and properties of the ANF receptor 4 Identify the source targets and effects of nitric oxide 5 Distinguish a The endogenous cellular precursor vs the pharmacologic precursor of NO b The Ca2dependent NO synthase of endothelial and nerve cells vs the Ca2 independent NO synthase of macrophages and neutorphils and liver cells c The local paracrine action of NO through diffusional movement vs the longrange endocrine action via hemoglobin as a carrier 6 Identify the three gases for which hemoglobin can serve as a carrier in the bloodstream S36 Signaling 03 Eicosanoids T 1 Define what is an essential fatty acid 2 Recognize the nomenclature of the three major classes of eicosanoids and distinguish their divergent pathways of biosynthesis 3 Identify the cyclooxygenase pathway in terms of the first enzyme 1 protein 2 activities and diagram how isomerases and reductases branch out into many derivatives Describe the basis of steroid and nonsteroidal antiinflammatory drugs Explain the basis of selective inhibition of the two isozymes of PGH synthase Give examples of the eicosanoids as potent physiologic agents with many different activities 20 9701 S37 Cardiovascular System 01 Cardiac Electrophysiology and the Cardiac Cycle T 1 Excitation of cardiac cells Ionic basis of the action potential in working muscle and Purkinje fibers Ionic basis of pacemaker potential and action potential in nodal fibers Hierarchy of pacemaker and conduction velocity Cardiac muscles as a function synctium Effect of acetylcholine and norepinephrine on pacemaker potential Dual reciprocal innervation and the regulation of heart rate Relationship of action potential to twitch contraction 2 Organization and synchronization of the heart beat a Spread of excitation in the heart b Autonomic effects on spread of excitation 3 Electrocardiogram 4 Cardiac Cycle masher S38 Cardiovascular System 02 Cardiac Output 1 T 1 Cardiac Histology a General plan 1 Endocardium 2 Myocardium 3 Epicardium b Arrangement of fibers c Atrial myocytes 2 Control of Cardiac Output Cardiac Output Stroke volume x Heart rate 3 Factors Influencing Stroke Volume a Starling s Law of the Heart preload 1 Definition 2 Starling curves 3 Ventricular compliance 4 Balance of output of right and left ventricles b Contractility 1 Definition 2 Starling curves 3 Causes of changes in contractility c Afterload 1 Definition 2 Effect of change in afterload on stroke volume 3 Compensation for increased afterload 4 Starling curves S39 Cardiovascular System 03 Cardiac Output 2 T 1 Pressure volume loops a Correlates with the cardiac cycle b Effect of preload c Effect of changes in contractility 2 Influence of heart rate on cardiac output a Contradictory effects of heart rate on cardiac output b Effect of electrical pacing on cardiac output c Effect of increased heart rate caused by sympathetic nerve stimulation d Predicting the effect of increased heart rate on stroke volume 3 Cardiac Energetics a Cardiac energy production b Cardiac energy consumption internal and external work 21 c Pressure work vs volume work d Effect of 1a e oad 2 heart rate 3 contractility e Double product S40 Cardiovascular System 04 The Systemic Circulation T 1 Blood vessels in the systemic circulation a General plan b Elastic arteries c Muscular arteries d Arterioles 2 How pressures are established in the cardiovascular system a Characteristics of blood vessels Mean circulatory filling pressure How the pump heart establishes the pressure profile ofthe systemic circulation Systolic and diastolic arterial pressure Pressure drop in the arterioles Pressure drop in the capillaries Pressure drop in the veins 3 Pressure and ow pro le in the systemic circulation 4 Systemic vascular resistance 5 Mean arterial pressure and pulse pressure Pulse pressure Systolic and diastolic pressure Mean arterial pressure Effect of changes in stroke volume heart rate and systemic vascular resistance 272099 995 S41 Cardiovascular System 05 Blood Volume and Venous Return T 1 Microanatomy of veins and venules a Medium veins b Venules 2 Blood volume and venous return a Distribution of blood volume 1Transmural pressure 2Changes with standing 3 Effects of respiration Venous return and cardiac output 1Transients 2 The vacuum cleaner experiment 3 Change in total blood volume 3 Pulmonary circulation a Pulmonary arterial pressure b Effect of increased cardiac output on pulmonary vascular resistance c Effect of hypoxia on pulmonary vascular resistance 039 L09 Cardiovascular System Lab T 1 Identify the tunics of a blood vessel correlate these tunics with the type of vessel and the function of the vessel 2 Correlate the ultrastructure of capillaries with their transport and other functions 3 Identify the regions of the heart and heart valve and correlate these with function 4 Identify Purkinje fibers and understand their function 22 S42 Cardiovascular System 06 Exchange of Substances Across The Capillary Walls T 1 Microanatomy of capillaries a b c d Vascular and tissue exchange of solutes C Capillary Filtration and Reabsorption CON P rthOO39mmlorthOO39m Composition of wall Continuous Fenestrated Sinusoidal or discontinuous Forces affecting water movement Starling forces Factors affecting capillary hydrostatic pressure Pc Factors affecting interstitial fluid hydrostatic pressure Pi Factors affecting capillary plasma oncotic pressure l39lc Factors affecting interstitial fluid oncotic pressure l39li The role of lymph flow Balance of Starling forces in the lungs ema Definition and general cause Edema resulting from increased venous pressure T Pc Safety factors against edema Edema resulting from hypoproteinemia T l39lc Edema resulting from lymphatic obstruction i F Edema resulting from injury or allergic reaction T Pc and T F S43 Cardiovascular System 07 Neural amp Hormonal Regulation of Blood Pressure amp Volume T 1 Celestial Committee on the Control of the Circulation 2 Arterial baroreceptor reflex a b Baroreceptor firing rate at different mean arterial and pulse pressures Response to activation of baroreceptors 3 Cardiopulmonary reflex 4 Effect of CBV on hormones 5 The long term regulation of arterial pressure a b Role of salt and water metabolism Cast of characters 1 Renin angiotensin aldosterone system 2 Antidiuretic hormone 3 Natriuretic hormones 4 Pressure diuresis 6 Stress of upright posture a b Initial cardiovascular response to standing Cardiovascular response to prolonged standing 1 Muscle pump 2 Respiratory pump 3 Salt and water metabolism S44 Cardiovascular System 08 Local Regulation of Blood Flow T 1 Reminder ofthe basic design of the control ofthe circulation 2 Basic mechanisms for local regulation of blood ow a b c Metabolic regulation Myogenic regulation Paracrine regulation 3 Categories of local regulation a b Active hyperemia Reactive hyperemia 23
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