Foundations - Learning Objectives for Final Exam

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Learning Objectives for Foundations Final Exam Intro to Foundations LO-01 Identify the expectations of the Foundation Block LO-02 Understand the general overview of the role of Foundations in the 4-Year Curriculum. LO-03 Identify the contact information of the Foundation Block Director and faculty. LO-04 Articulate the course objectives of the Foundation Block. LO-05 Navigate Foundations course site on MedLearn. LO-06 Acknowledge responsibility to engage in sessions with respect and integrity for self and others. LO-07 Identify opportunities for self-directed learning within the Foundations Block. Intro to Physiology LO-01 Define homeostasis. LO-02 Describe a homeostatic process in the human body. Give specific examples of how all the organs work together. LO-03 Describe how dysfunction in a single organ can lead to dysfunction of another organ. LO-04 List the steps associated in the loss of homeostasis in heat stroke. Intro to Principles of Pharmacology LO-01 Define the terms Pharmacology, Pharmacokinetics, Pharmacodynamics, Toxicology and Pharmacotherapeutics. LO-02 Define the three general mechanisms of drug actions LO-03 Foundations Page 1 LO-03

Define what it takes for a drug to have affinity for a receptor. LO-04 Compare and contrast therapeutic index vs therapeutic window. LO-05 Apply in-class principles to heat stroke. IL Drugs in Foundations 1. Compare and contrast NSAIDs and steroids including the mechanism of action, what they are used for and their side effects. 2. Describe the mechanism whereby antibiotics act to inhibit bacterial growth (no need to memorize proprietary names-yet). 3. Associate drugs listed in the tables with type of pathogen they are used to treat. 4. Describe the mechanism of action of the drugs used for Acne and beware of life threatening side effects (i.e., teratogen and severe depression-suicide). IL Cell Signaling Basics 1. Differentiate among autocrine, juxtacrine, paracrine and endocrine signaling, and give examples of each. 2. Describe the four main types of signaling pathways and give examples of each. 3. Define the following terms in the context of cell signaling, and diagram their interrelationships: ligand, receptor, kinase, phosphatase, amplification, regulation, G protein, phosphorylation, second messenger, cascade, cell surface receptor, intracellular receptor. Clinical Genetics LO-01 Define the following terms and identify examples of each: locus, genotype, phenotype, allele, homozygote, heterozygote, hemizygote, genetic heterogeneity (allelic and locus), variable expression, pleiotropy, reduced penetrance, consanguinity, Single Nucleotide Polymorphism (SNP), copy number variant (CNV), Variant of Uncertain Significance (VUS/VOUS). LO-02 Generate differential diagnoses and risk assessments from clinical assessment. LO-03 Understand the mechanisms of pedigree formation, including limitations in the current standard process. LO-04 Using information from a medical history and pedigree, assign a disorder to an autosomal dominant, autosomal recessive, X-linked dominant and X-linked recessive inheritance pattern.

Foundations Page 2 LO-05 Calculate the risk of having an affected child for selected individuals in pedigrees of autosomal dominant, autosomal recessive, and X-linked inheritance. The Human Genome & Mutation LO-01 Explain the following terms: genome; gene; exon; intron; non-coding RNA; epigenetics; penetrance; variable expressivity; circulating cell-free DNA; chromatin; histone; linkage disequilibrium; monogenic disorder; complex multifactorial disorder LO-02 Describe the structures and functions of the following components of the human genome: (1) Gene-coding sequences (protein-coding & non-coding); (2) Gene-related sequences (introns & UTRs); (3) Transcriptional regulatory elements; (4) Intergenic repetitive DNA sequences (retroposons, DNA transposons, simple repeats; large repeats); mitochondrial genome; cell-free circulating DNA LO-03 Summarize the steps in the packaging of the nuclear genome from chromatin to chromosomes LO-04 Select the most appropriate clinical DNA sequencing methods for detection of different types of disease-associated gene mutations LO-05 List the key properties of complex multifactorial diseases LO-06 Identify the different types of mutations that are commonly found in the genome LO-07 Discuss the classification of gene mutations associated with familial breast cancer Evidence Based Decision Making 101 LO-01 Become familiar with the vocabulary terms. LO-02 Identify the components of a good clinical question and construct a clinical question using these components. LO-03 Identify the four steps of the practice of EBM. LO-04 Given a series of clinical research abstracts, rank them in order of the level of evidence each provides in support of a specific clinical question assuming they are well done studies.

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LO-05 Be able to construct a clinical question using the PICO Model. Foundations Page 3 Be able to construct a clinical question using the PICO Model. LO-06 Apply a “best practice model” to make a decision about a clinical question. LO-07 Reconstruct the Evidence Pyramid and explain the rationale behind each level’s rank. Considering Cultural Humility and Health Inequity LO-01 Explore the complexities of collective and individual identity in the United States and discuss your identity in a small group. LO-02 Discuss bias, discrimination, and racism’s effects on health and health care. LO-03 Define “health disparities” and their effects on historically marginalized populations in the United States. LO-04 Describe models for culturally responsive patient care and practice using a framework for engaging in conversations with patients. Arizona Population Health LO-01 Learn the basic geography, history, and demographics of Arizona. LO-02 Describe the differences between individual vs. population-level approaches to health. LO-03 Summarize how population health can be used in medical care. LO-04 Understand the levels of prevention and how it connects to population health. LO-05 Discuss the needs of key populations in Arizona and consider how community engagement could improve population health. Intro to Anatomy LO-01 Describe and demonstrate standard anatomical position

LO-02 Describe the planes of anatomical section Foundations Page 4 LO-03 Apply the planes of anatomical section to medical imaging LO-04 Apply the following terms to describe the position of anatomical structures: anterior/posterior, rostral/caudal, superior/inferior, medial/lateral, proximal/distal, dorsum/palmar/plantar, deep/superficial/intermediate, external/internal, unilateral/bilateral, contralateral/ipsilateral. LO-05 Describe the distribution and function of the following organ systems: musculoskeletal, integumentary, nervous, circulatory, respiratory, lymphatic, digestive, urinary, endocrine, reproductive. LO-06 Compare and contrast the function and distribution of the central nervous system, somatic peripheral nervous system, visceral peripheral nervous system6. Compare and contrast the function and distribution of the central nervous system, somatic peripheral nervous system, visceral peripheral nervous system LO-07 Apply the concepts of deep and superficial to explain fascial layers and structural layers LO-08 Compare and contrast the structure of a cavity, a bursa, and a potential space LO-09 Compare and contrast relationships between organ systems in 2 examples: a muscular compartment and the small intestine LO-10 Explain the clinical relevance of anatomical variation Major Organs and Vessels (Gross Anatomy) LO-01 Identify and describe location of the structures listed below relative to one another using proper anatomical terminology (anterior-posterior, medial-lateral, superior-inferior, proximal-distal, superficial-deep). LO-02 Deduce consequences of damage based upon relationships and basic functions (use knowledge of normal to predict abnormal and vice versa). LO-03 Be able to identify the bold-face organs on axial CT scans. (See lab notes for structure list.)

IL Tissue Types LO-01 Describe characteristics that distinguish the four tissue types from each other. Apply these Foundations Page 5 Describe characteristics that distinguish the four tissue types from each other. Apply these features to identifying tissue types in tissue sections. LO-02 Apply the standard classification scheme to identifying different epithelia. Relate function of different types of epithelia to structure. LO-03 Explain the concept of epithelial cell polarity and discuss its importance in epithelial function. LO-04 Describe structure and function of the main apical, basal and lateral membrane specializations of epithelial cells. LO-05 Describe the composition of connective tissue proper including fibers, ground substance and cells. Relate structure to function LO-06 Describe the role of connective tissue in support and defense including metabolic support and inflammation. LO-07 List resident and itinerant cells in connective tissue. Briefly describe the function of resident cells. LO-08 Describe the path of white blood cell circulation, and entry into connective tissues. LO-09 Compare and contrast cardiac, skeletal and smooth muscle in terms of structure and function, and distinguish these tissues in sections. LO-10 List components of the central and peripheral nervous systems. Identify peripheral nerves, parasympathetic ganglia, and their components in tissue sections. IL Organ Architecture LO-01 Define architecture and cytology. Compare and contrast hollow and solid organs in terms of architecture. LO-02 Describe basic functions of digestive tract, lung airways, pancreas, liver, and kidney, relating

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function to structure where possible. LO-03 Describe/identify the following structures where they occur: mucosa; lamina propria; submucosa, muscularis, serosa; adventitia, including the sublayers and components of each. LO-04 Explain the concept of dual blood supply as it applies to lung and liver, and name the vessels involved. Foundations Page 6 LO-05 Compare and contrast the layers and sub-layers of blood vessels with that of hollow organs such as the digestive tube. LO-06 Distinguish medium and large arteries, arterioles, medium veins, venules, and capillaries in sections. Identify the different layers and sublayers and their components. LO-07 Describe the histological organization of the pancreas. Distinguish parenchyma and stroma. Identify lobules, acinar cells, acini and ducts in sections of pancreas. LO-08 In the liver, outline blood flow through portal tracts, sinusoids and central veins. Contrast with flow in bile ducts. Identify these structures in sections. LO-09 In the kidney, distinguish glomeruli (and components, in electron micrographs), kidney tubules, blood vessels and interstitium. LO-10 Identify bronchi, bronchioles and alveoli in lung. Compare in terms of structure and function. IL Pathologic Basis of Clinical Medicine LO-01 Understand the role of pathology in prevention, diagnosis, treatment, and management of disease. LO-02 Describe the basic mechanisms of disease. LO-03 Describe the three basic competencies in pathology. LO-04 Describe the approach used in the diagnosis of neoplasms and other pathologies, including the use of tumor markers. TL Imaging 1

LO-01 Students will explain the advantages of a Chest Radiograph (CXR) in an Emergency Room patient with shortness of breath versus CT scan. LO-02 Students will explain the basics of reading a CXR including identification of critical anatomical markers. LO-03 Students will identify conditions where CT scan is superior to CXR. Foundations Page 7 Students will identify conditions where CT scan is superior to CXR. LO-04 Students will identify major abdominal organs on abdominal XR. LO-05 Students will identify the liver, spleen, pancreas, kidney, stomach, and colon on an abdominal CT scan with oral and intravenous (IV) contrast. LO-06 Students will describe the advantages and disadvantages of Ultrasound and CT in screening for abdominal trauma. Intro to Immunology - Overview and Innate Immunity LO-01 Describe the general features that distinguish innate versus adaptive immunity (major cell types, kinetics of response, features of response, receptor families important for response). LO-02 Describe the properties of epithelial surfaces that contribute to innate immunity. LO-03 Describe the roles of complement components in the innate immune response. Explain how the system is triggered and what it does to combat infection. LO-04 Describe the properties and roles in immunity of key innate cells such as neutrophils and macrophages. LO-05 Explain the basic pathway of an acute inflammatory response; understanding the roles of key chemical mediators and cell types. LO-06 Explain the mechanisms used by the innate immune system to recognize “non-self”. Describe the function of the TLR and NLR families of innate receptors, and explain the importance of cellular damage sensing in innate immunity.

Intro to Immunology - Lymphocytes LO-01 Define the general functions of the major cell types involved in adaptive immune response (B cells, T cells, and antigen-presenting cells). LO-02 Explain the clonal selection model of adaptive immunity. LO-03 Describe the structure and features of antigen receptors on B and T cells, including the different protein chains and domains. Foundations Page 8 LO-04 Explain the molecular process by which antigen receptor diversity is generated for B and T cells (VDJ recombination). LO-05 Explain the molecular process of isotype switching (class switching) of immunoglobulins. LO-06 Describe the properties and functions of each antibody isotype. LO-07 Identify the effector functions of Helper, Cytotoxic, and Regulatory T cells, including the major sub-lineages of Helper T cells. LO-08 Describe the cell types and steps involved in T cell activation, including the roles of APCs and costimulation. LO-09 Describe how antigenic peptides for MHC Class I and Class II are generated, and what this means for immune surveillance. LO-10 Explain the structural differences between MHC Class I and MHC Class II. Histology Lab - Tissue Types LO-01 Describe characteristics that distinguish the four tissue types from each other. Apply these features to identifying tissue types in tissue sections. LO-02 Apply the standard classification scheme to identifying different epithelia. Relate function of different types of epithelia to structure. LO-03

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Explain the concept of epithelial cell polarity and discuss its importance in epithelial function. LO-04 Describe structure and function of the main apical, basal and lateral membrane specializations of epithelial cells. LO-05 Describe the composition of connective tissue proper including fibers, ground substance and cells. Relate structure to function LO-06 Describe the role of connective tissue in support and defense including metabolic support and inflammation. LO-07 List resident and itinerant cells in connective tissue. Briefly describe the function of resident cells. Foundations Page 9 List resident and itinerant cells in connective tissue. Briefly describe the function of resident cells. LO-08 Identify the following in peripheral blood smears: red blood cell, neutrophil, lymphocyte, eosinophil, basophil, monocyte, platelet. Describe relative proportions of each of these cell types in a normal peripheral blood smear. LO-09 Describe the path of white blood cell circulation, and entry into connective tissues. LO-10 Compare and contrast cardiac, skeletal and smooth muscle in terms of structure and function, and distinguish these tissues in sections. LO-11 List components of the central and peripheral nervous systems. Identify peripheral nerves, parasympathetic ganglia, and their components in tissue sections. Histology Lab - Organ Architecture LO-01 Define architecture and cytology. Compare and contrast hollow and solid organs in terms of architecture. LO-02 Describe basic functions of digestive tract, lung airways, pancreas, liver, and kidney, relating function to structure where possible. LO-03 Describe/identify the following structures where they occur: mucosa; lamina propria; submucosa, muscularis, serosa; adventitia, including the sublayers and components of each. LO-04 Explain the concept of dual blood supply as it applies to lung and liver, and name the vessels

involved. LO-05 Compare and contrast the layers and sub-layers of blood vessels with that of hollow organs such as the digestive tube. LO-06 Distinguish medium and large arteries, arterioles, medium veins, venules, and capillaries in sections. Identify the different layers and sublayers and their components. LO-07 Describe the histological organization of the pancreas. Distinguish parenchyma and stroma. Identify lobules, acinar cells, acini and ducts in sections of pancreas. LO-08 In the liver, outline blood flow through portal tracts, sinusoids and central veins. Contrast with flow in bile ducts. Identify these structures in sections. LO-09 Foundations Page 10 LO-09 In the kidney, distinguish glomeruli (and components, in electron micrographs), kidney tubules, blood vessels and interstitium. LO-10 Identify bronchi, bronchioles and alveoli in lung. Compare in terms of structure and function. CBL: Trauma LO-01 Integrate major organs anatomy and imaging principles to case scenarios of trauma, including stab wound and gun shot wound. LO-02 Apply immunology principles to adverse event scenario Pharmacodynamics: Drug Receptors, Signal Transduction and Dose-Response LO-01A Define the terms Pharmacodynamics and Pharmacotherapeutics. LO-02A Describe the chemical nature of receptors. LO-03A Explain the chemical interaction between drugs and receptors and what it takes for a drug to have affinity for a receptor. LO-04A Give evidence for the existence of receptors.

LO-05A Describe the components of drug receptor systems. LO-06A Define agonist, partial agonist and antagonist drugs in terms of affinity and efficacy. LO-07A Define potency, efficacy, competitive antagonist and noncompetitive antagonist. LO-08A Define signal transduction. LO-09A Describe (draw out) Gs, Gi and Gq protein coupling. LO-10A Describe how a G-protein can influence gene transcription. LO-11A Describe how a G-protein can alter ion channel activity. Foundations Page 11 LO-12A Describe how kinase receptors result in signal transduction. LO-13A Describe the mechanism of corticosteroid receptors. LO-14B Be able to plot data on a typical log dose-response curve. LO-15B Understand how dose-response curves can be used to determine potency, efficacy, and the nature of drug interactions. LO-16B Define graded and quantal dose-response curves. LO-17B Explain why potency is often expressed as D50 or ED50. LO-18B Compare and contrast “therapeutic window” and "therapeutic index", and know how to calculate both. Foundations of Embryology and Early Development LO-01 Relate general anatomy of an embryo to postnatal anatomy using correct directional terminology. LO-02 Describe the spatial and functional relationships between the embryo, extraembryonic tissue, and maternal tissue.

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LO-03 Describe the relevance of apoptosis, growth factors, transcription factors, and induction to normal & pathological development. LO-04 Define which germ layer(s) contribute to formation of a given organ LO-05 Describe the general timeline of human development. LO-06 Describe the clinical relevance of mutations, numeric/structural chromosomal abnormalities, critical periods, teratogen exposure, congenital infection, and multifactorial inheritance. LO-07 Apply the following terms for developmental injury: malformation, disruption, deformation, aplasia, hypoplasia, dysplasia, field defect, syndrome, sequence, association. LO-08 Describe the multiplication and distribution of cells in the embryo from zygote to blastocyst. Foundations Page 12 Describe the multiplication and distribution of cells in the embryo from zygote to blastocyst. LO-09 Compare and contrast the development of single zygotes, dizygotic twins, and monozygotic twins. LO-10 Describe the movement of the embryo from fertilization to implantation, including normal and pathological implantation locations. LO-11 Describe the development of the 2-layered embryonic disc and its spatial relationships with the amnion, primary yolk sac, Cyto-trophoblast, and syncytio-trophoblast. LO-12 Describe the function of the primitive streak and its significance to sacrococcygeal teratomas and laterality defects. LO-13 Describe the movement of cell populations to produce the three germ layers of the embryo (ectoderm, mesoderm, endoderm). Hemoglobin: Red Blood Cells and Oxygen Transport LO-01 Differentiate between reticulocytes and erythrocytes, and discuss how reticulocyte and erythrocyte count may be used diagnostically. LO-02 Describe the role of band 3 protein (anion exchange protein), and cytoskeletal proteins associated with

the red blood cell membrane. LO-03 Describe similarities and differences between Myoglobin and Hemoglobin. LO-04 Describe the beta and alpha globin gene clusters, and identify the different globin chain compositions that comprise HbA1, HbA2 and HbF. LO-05 Discuss how the R(elaxed) and T(ense) configurations of Hb relate to the positioning of the heme iron, the role of the proximal histidine, and the binding or releasing of oxygen. LO-06 Describe how cooperative binding of oxygen by hemoglobin improves its effectiveness as an oxygen transporter. LO-07 Discuss the physiological significance of protons (Bohr Effect), carbon dioxide, BPG (2,3- bisphosphoglycerate) and the presence of the g-subunit rather than the b-subunit in HbF on the affinity of Hb for oxygen and under what circumstances these effects are important. LO-08 Discuss how carbon monoxide (CO) competes with oxygen for binding to Hb and how its greater Foundations Page 13 Discuss how carbon monoxide (CO) competes with oxygen for binding to Hb and how its greater affinity relative to O2 is reduced by the distal histidine. LO-09 Describe the relationship between hemoglobin and acid-base homeostasis. LO-10 Describe the molecular genetic basis of the various thalassemias, the genotypephenotype relationships in these diseases and the aberrant hemoglobins that are produced. Intro to Blood - Part 1 LO-01 Describe the components of blood. LO-02 Describe the morphologic features that characterize differentiation of marrow precursors cells to the mature cells seen in the blood and the approximate time this process takes for platelets, RBCs, and neutrophils. LO-03 Define anemia and outline the classification of anemia. LO-04 Describe the components of the hemostasis system and their functions. LO-05

Compare and contrast disorders of primary hemostasis (platelet, vessel wall) and secondary hemostasis (coagulation factor) in terms of type of bleeding (location, severity) and onset of bleeding. LO-06 Describe the two main causes of thrombocytopenia. LO-07 Compare and contrast von Willebrand disease and Hemophilia A in terms of type of bleeding, defect, lab features and treatment. Intro to Anemias LO-01 Define anemia with its signs and symptoms LO-02 Describe the approach to anemia classification LO-03 Become familiar with the diagnostic tests in work up of a patient with anemia a. Red cell incises b. Reticulocyte count and advanced red cell parameters c. Peripheral blood smear assessment LO-04 Foundations Page 14 LO-04 Describe the morphologic findings and diagnostic work up of: a. Anemia of inflammation b. Thalassemia and hemoglobinopathies c. Hemolysis, immune and non-immune mediated hemolysis d. Anemia due to RBC membrane structural defects and enzyme defects Cardiovascular Physiology LO-01 Identify the 3 basic components of the cardiovascular system. LO-02 Describe the heart as a single pump, then as 2 separate pumps. LO-03 Define: Heart Rate, Stroke Volume, Cardiac Output, Inotropy, Preload, Afterload. LO-04 Identify p-wave, QRS complex, T-wave, intervals and segments on a basic ECG trace. LO-05 Describe the major classes of vessels and classify them by their major “job”. LO-06 Describe how Cardiac Output and Systemic Vascular Resistance control blood pressure and how

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changes in either (or both) can lead to hypertension. Active Learning Embryology LO-01 Evaluate the relative impact of teratogen exposure or congenital infection at different points in development. LO-02 Evaluate which germ layers would be involved in a given clinical scenario. LO-03 Infer which anatomical structures may be impacted by injury to a particular germ layer. LO-04 Differentiate between different types of twinning based on morphology and timing of division. LO-05 Apply material from the live foundations of development/early development lecture to a given clinical scenario. IL Cell Injury and Death LO-01 Explain why an elevated blood level of cardiac troponin is used as an indicator of a myocardial infarct. Foundations Page 15 LO-02 Differentiate the different types of necrosis by their etiology and morphologic features. LO-03 Summarize the molecular changes occurring in cells exposed to hypoxia and relate these changes to the microscopic appearance of reversibly, and irreversibly, injured cells. LO-04 Understand the role of glutathione in cells. LO-05 Describe the mechanism by which cyanide injures cells, and explain why N-acetylcysteine is used to treat acetaminophen poisoning. LO-06 Summarize key differences between necrosis and apoptosis. Thrombosis, Embolism and Infarction LO-01 Define thrombosis, differentiate hemostatic versus pathologic thrombosis, and summarize the 3 major predisposing factors.

LO-02 Describe the features that differentiate a true thrombus from a postmortem clot. LO-03 Describe the mechanism whereby factor V Leiden and the prothrombin gene mutation lead to hypercoagulability. LO-04 Describe the potential fates of a thrombus and their clinical significance. LO-05 Define embolism and describe different types (thromboemboli, fat, air, amniotic fluid) and their causes/risk factors. LO-06 Describe the pathophysiologic consequences and potential outcomes of pulmonary embolism. LO-07 Define infarction and describe the clinical significance. LO-08 Compare and contrast the gross and microscopic features of red and white infarcts; explain why they occur in different organs. LO-09 Summarize the factors that influence the development of an infarct. CBL: Autonomics Foundations Page 16 CBL: Autonomics LO-01 Apply principles of pharmacodynamics to the Autonomic Nervous System, including autonomic receptors within the cardiovascular system Pathology Lab - Thrombosis, Embolism and Infarction LO-01 Identify/describe the microscopic and gross pathologic changes that occur in tissues with hemorrhagic or pale infarcts. LO-02 Distinguish a thrombus from a postmortem clot based on microscopic and gross pathologic features. LO-03 Describe the general microscopic and gross features of an atherosclerotic plaque (fibrous cap, cholesterol clefts, calcification, intimal location). CBL: Hypertension

LO-01 Define Hypertension. LO-02 Explain lifestyle changes that should be instituted in patients with hypertension. LO-03 Describe the mechanism of action of Lisinopril and HCTZ in the treatment of hypertension. LO-04 Define shock. LO-05 Describe the first sympathetic nervous system response to hypovolemic shock and the effect produced on the arteriole and the heart. CBL: Thrombosis , Emboli and Infarction LO-01 Define virchows triad for clotting. LO-02 Describe the clinical presentation and physical findings of Deep Vein Thrombosis (DVT) of the lower extremity. LO-03 Describe the risk factors for DVT in trauma patients. LO-04 Describe the imaging tool and findings for DVT of the lower extremity. Foundations Page 17 Describe the imaging tool and findings for DVT of the lower extremity. LO-05 Describe the risk factors for arterial embolism. LO-06 Describe the clinical presentation and physical findings in arterial embolism of the lower extremity. LO-07 Describe the risk factors for arterial thrombosis of the lower extremity. LO-08 Describe the clinical presentation and physical findings for arterial thrombosis of the lower extremity. Respiratory Physiology LO-01 Describe the anatomy of the respiratory system (work from where air enters the body and end at

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the alveoli). LO-02 Contrast the mechanics of inspiration and expiration. LO-03 List and define the volumes and capacities of the lungs. Intro to Blood 2 LO-01 Describe the components of blood. LO-02 Describe the morphologic features that characterize differentiation of marrow precursors cells to the mature cells seen in the blood and the approximate time this process takes for platelets, RBCs, and neutrophils. LO-03 Describe the morphologic features of the white blood cells in the peripheral blood and be able to identify them. LO-04 Describe the function of the different WBCs. LO-05 Relate major causes of leukocytosis and leukopenia to functions of white blood cells. LO-06 Describe the significance of a left-shift of granulocytes in the blood. Foundations Page 18 Intro to Microbials LO-01 Differentiate between colonization and infection. LO-02 Discuss the general mechanisms of actions of antibacterials, antivirals, antifungals, antiprotozoals, and anthelmintics LO-03 Explain the mechanisms of action for antibiotic inhibitors of protein synthesis, and be able to list specific examples of antibiotics LO-04 Discuss the killing characteristics of antibacterials LO-05 Discuss the mechanisms of antibiotic resistance, its importance in medicine, and how to combat it

Protein Synthesis and Structure LO-01 Describe the role of mRNA, tRNA, and ribosomes in protein synthesis and the main steps of protein translation. LO-02 Describe the types of post-translational modifications and the nature of the role of each. LO-03 Outline the sequence of events in the synthesis and processing of insulin including differentiating its precursor forms. LO-04 Describe the regulation of the synthesis and secretion of insulin by glucose. LO-05 Describe the steps and relevant cofactors in the synthesis and processing of collagen including the post-translational modifications of amino acid residues during its maturation (i.e., proteolysis, hydroxylation, glycosylation, and oxidation). The Immune Response LO-01 Describe the patterns of lymphocyte circulation throughout the body (especially between the blood and lymphatics) and relate these to immune surveillance of the body. LO-02 Describe the major steps involved in the generation of B and T cell responses, including cells and molecules involved, anatomical locations, and effector functions. LO-03 Foundations Page 19 LO-03 Describe the kinetics and dynamics of B and T cell responses. LO-04 Explain the concept of affinity maturation and describe the molecular mechanism. LO-05 Define the functions of Natural Killer (NK) cells and explain how they recognize their targets. LO-06 Describe the acute-phase response, including the cytokines the induce it and their effects. LO-07 Explain the concepts of active and passive immunization and provide examples of each. IL: Microbiology Overview

LO-01 Describe the organism factors (e.g., virulence) and host factors (e.g., age, nutritional status) that determine susceptibility to an infectious disease. LO-02 Understand the differences between prokaryotes and eukaryotes. LO-03 Identify characteristics of bacteria, viruses, fungi, and parasites that help in their identification. LO-04 Describe the factors of bacteria, viruses, fungi, and parasites that contribute to their pathogenesis. LO-05 Describe important factors that affect the diagnosis of bacteria, viruses, fungi, and parasites. Study Designs 101 LO-01 Become familiar with the vocabulary terms LO-02 Identify the fundamental characteristics of the following study designs and demonstrate an understanding of their relative strengths and weaknesses: a. Descriptive: Case Report, Case Series, Cross-sectional study b. Observational – Cohort and Case-control c. The Randomized Controlled/Clinical Trial (RCT), d. Systematic Review LO-03 Demonstrate an understanding of what the discipline of Clinical Epidemiology is and how clinical research differs from basic science research. LO-04 Demonstrate a basic understanding of how incidence, prevalence, attributable risk and mortality rates are used in estimating the probability of disease on populations and individuals. Foundations Page 20 LO-05 Demonstrate an understanding of what Relative Risk (RR) and Odds Ratio (OR) mean and how they are similar and different. LO-06 Demonstrate the ability to construct a 2x2 table given data from a Case-control study or Cohort study and where appropriate, use it to calculate: a. Absolute risk b. Relative Risk c. Odds Ratio d. Absolute Attributable Risk e. Relative Attributable Risk LO-07

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Describe the characteristics of common study designs to be used in answering clinical questions of the studies discussed in EBDM 101 a. What is the clinical question? b. What kind of patients are enrolled? c. What intervention are administered to the subjects? d. What intervention, if any, is given to the control subjects? e. What outcomes are measured? f. What are the conclusions drawn by the investigators? Diagnostic Tests and Probability LO-01 Become familiar with the vocabulary terms. LO-02 Identify why diagnostic tests are useful in clinical decision making. LO-03 Describe the performance characteristics of diagnostic tests below and what probabilities they reflect. a. Sensitivity b. Specificity c. Positive Predictive Value d. Negative Predictive Value LO-04 Given data from a hypothetical study, construct a 2 x 2 table to determine the performance characteristics of a hypothetical diagnostic test. LO-05 Describe what a “Gold Standard” reference test is and when it is appropriately used. LO-06 Demonstrate a basic understanding of a ROC curve and the tradeoff between sensitivity and specificity. Foundations Page 21 CBL: Airway Disease LO-01 Explain the terms tidal volume (TV), residual volume (RV), inspiratory reserve volume (IRV), expiratory reserve volume (ERV), vital capacity (VC) LO-02 Explain the clinical significance of testing for Forced Expiratory Volume at 1 second (FEV1) in a patient with a long history of smoking. LO-03 Compare and contrast chronic obstructive pulmonary disease (COPD) and asthma as obstructive disease.

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LO-04 Describe what asthma and emphysema have in common to be grouped as obstructive diseases. LO-05 Describe the basic pathophysiology of asthma. LO-06 Describe the basic pathophysiology of COPD. LO-07 Interpret basic pulmonary functions using TV, VC FEV1, TLC and FEV1/FVC in asthma and emphysema. Compare and contrast PFTs in these diseases. LO-08 Understand the impact on PFT that autonomic medications for asthma and COPD have before and after treatment. IL: Acute Inflammation LO-01 Explain the three major components of acute inflammation. LO-02 Describe four common types of stimuli that trigger acute inflammation. LO-03 Describe the various types of extracellular fluid collections, including transudate, exudate, edema and pus. LO-04 Understand the two major results of the vascular response in acute inflammation to be vasodilation and increased vascular permeability, and describe the forces favoring fluid movement out of vessels. LO-05 Name the chemical mediator commonly implicated in the primary, transient vascular permeability response and identify the type of blood vessel in which increased permeability primarily occurs. Foundations Page 22 LO-06 Know the sequence of events in leukocyte extravasation, and explain how adhesion molecules are involved at most steps. LO-07 Explain the three main steps of phagocytosis, and describe four processes that are important in the third step (killing and degradation of microbes). LO-08 Name two diseases that occur due to defects in leukocyte function. LO-09

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Know the two main types of vasoactive amines, their source and explain their main effects. LO-10 Know the two main pathways of the arachidonic acid cascade and describe where anti inflammatory medications act in the cascade to inhibit the production of prostaglandins and leukotrienes. LO-11 Explain how nitric oxide acts as an endogenous regulator of inflammation. LO-12 Know the two main cytokines involved in inflammation and describe their major effects. LO-13 Recognize the complement, kinin and clotting systems as enzyme cascades that can act to modify the inflammatory response. LO-14 Explain the four common morphologic patterns of acute inflammation in tissues, and be able to give an example of each pattern. LO-15 Describe the three main outcomes of acute inflammation and explain factors favoring each outcome. Explain why some types of ongoing or repeated injury responses may display a mixed (both acute and chronic) inflammatory picture. IL: Chronic Granulomatous Inflammation, Tissue Regeneration, Wound Healing LO-01 Define chronic inflammation. LO-02 Describe three major causes of chronic inflammation, and be able to give an example of each. LO-03 Describe the morphologic features of chronic inflammation, including the predominant cell types. LO-04 Describe the main functions of macrophages in chronic inflammation. Foundations Page 23 LO-05 Understand that unregulated inflammation can cause tissue damage and identify two types of substances macrophages secrete that can injure host tissues. LO-06 Define granulomatous inflammation (i.e. formation of granulomas) and recognize granulomas in tissue. LO-07 Know the two main types of granulomas and list the common causative agents of granuloma formation.

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LO-08 Diagram the dynamic cellular events and mediators involved in granuloma formation. LO-09 Understand the relationship between blood monocytes, macrophages, epithelioid histiocytes and giant cells. LO-10 Describe three common fates of granulomas. LO-11 Compare and contrast tissue regeneration with healing by scar formation. LO-12 Explain the differences between embryonic and adult stem cells. LO-13 Know the main growth factors involved in tissue regeneration and repair. LO-14 Know the main components of granulation tissue and be able to recognize its appearance in tissue. LO-15 Explain two separate mechanisms of angiogenesis. LO-16 Explain the three main processes in scar formation. LO-17 Contrast wound healing by first intention to healing by second intention. LO-18 Recognize the main systemic and local factors that influence wound healing and describe three complications of wound healing. LO-19 Explain the main way in which fibrosis associated with chronic inflammatory conditions differs from healing of a cutaneous wound. Foundations Page 24 IL: Immune Organs LO-01 Outline the path of lymph flow, including the major lymph vessels and the regions they drain. Explain a major clinical implication of the asymmetric pattern of lymph drainage. LO-02 Describe the pathways that lymphocytes use to travel between blood and tissues, and compare to pathways used by other WBCs.

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LO-03 Explain the difference between primary and secondary lymphoid organs. LO-04 Identify diffuse lymphoid tissue and lymphoid follicles in histological sections. Identify the following structures in follicles: high endothelial venules, mitotic figures, macrophages, lymphocytes. LO-05 Describe the structure of lymph nodes, spleen, and tonsils. Identify these organs in histological sections. Relate structure to function. LO-06 Explain the special anatomic features that reflect the function of lymph nodes as filters of lymph, and spleen as a filter of blood. Apply this information to understanding causes of lymphadenopathy and splenomegaly. LO-07 Distinguish a bone marrow smear from a normal peripheral blood smear. LO-08 Distinguish mature from immature cells in the bone marrow slide. LO-09 Identify the following in tissue sections: neutrophils, eosinophils, macrophages, lymphocytes, plasma cells CBL: Pneumonia LO-01 Describe the pathogenesis of the various infections that involve the lower respiratory tracts LO-02 Compare and contrast clinical presentations, diagnosis, and treatment of bacterial, viral (influenza and SARS-CoV-2), fungal pneumonias (coccidioides, histoplasma, blastomyces) and tuberculosis LO-03 Describe the approach to antibiotic therapy in a patient with community-acquired pneumonia CBL: O2 Dissociation Cases Foundations Page 25 LO-01 Explain the terms tidal volume (TV), residual volume (RV), inspiratory reserve volume (IRV), expiratory reserve volume (ERV), vital capacity (VC) LO-02 Explain the significance of oxygen saturation and hematocrit and hemoglobin levels in O2 delivery LO-03

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Describe the O2 dissociation curve and understand what causes left and right shifts LO-04 Explain respiratory changes at high altitude and what causes HAPE LO-05 Describe issues associated with CO poisoning Histology Lab Immune Organs LO-01 Outline the path of lymph flow, including the major lymph vessels and the regions they drain. Explain a major clinical implication of the asymmetric pattern of lymph drainage. LO-02 Describe the pathways that lymphocytes use to travel between blood and tissues, and compare to pathways used by other WBCs. LO-03 Explain the difference between primary and secondary lymphoid organs. LO-04 Identify diffuse lymphoid tissue and lymphoid follicles in histological sections. Identify the following structures in follicles: high endothelial venules, mitotic figures, macrophages, lymphocytes. LO-05 Describe the structure of lymph nodes, spleen, and tonsils. Identify these organs in histological sections. Relate structure to function. LO-06 Explain the special anatomic features that reflect the function of lymph nodes as filters of lymph, and spleen as a filter of blood. Apply this information to understanding causes of lymphadenopathy and splenomegaly. LO-07 Distinguish a bone marrow smear from a normal peripheral blood smear. LO-08 Distinguish mature from immature cells in the bone marrow slide. LO-09 Identify the following in tissue sections: neutrophils, eosinophils, macrophages, lymphocytes, plasma cells. Foundations Page 26 plasma cells. Pathology Lab: Inflammation LO-01 Identify/describe the microscopic and gross pathologic changes in tissue with acute and chronic inflammation.

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LO-02 Identify (when possible) the underlying process that induced the inflammation. LO-03 Describe the cellular events that produced the microscopic appearance observed (chemotaxis, margination, etc.). LO-04 Relate the microscopic findings to gross and clinical findings. TL: Imaging and Labs LO-01 The student will identify the structures in the right upper quadrant (RUQ) of the abdomen. LO-02 The student will be able to explain why Ultrasound is a better exam than CT scan for demonstrating gallstones. LO-03 The student will be able to interpret the results of a Liver Panel (Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Bilirubin (BR), Alkaline Phosphatase (ALP). LO-04 The student will explain how the movement of a gallstone out of the gallbladder and into the common duct changes the values of the different components of the liver panel. LO-05 The student will be able to classify the type of jaundice, (pre-hepatic, hepatic and post – hepatic) based on the liver panel in a jaundiced patient. LO-06 The student will know the difference between labs that reflect liver function and those that reflect liver cell death. IL: Gene Expression & Regulation - Part 1 LO-01 Describe the role of the core and regulatory elements in transcription initiation. LO-02 Explain how DNA methylation and chromatin modifications control transcription initiation. LO-03 Foundations Page 27 LO-03 Explain how estrogen regulates the transcription of estrogen-responsive gene expression. LO-04 Describe how the transcription factors Myc-Max-Mad and p53 control cell growth and

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proliferation and how dysregulation leads to abnormal cell proliferation and cancer LO-05 Outline the structure of the beta-globin locus and how the genes are controlled by the LCR super enhancer LO-06 Explain how the nucleotide repeat expansion mutation in the FMR1 gene causes fragile X syndrome IL: Gene Expression & Regulation - Part 2 LO-01 Describe how alternative mRNA splicing regulates gene expression and how aberrant mRNA splicing can lead to disease LO-02 Outline how the translation of ferritin mRNA is regulated by the iron response element binding protein LO-03 Discuss the role of nonsense-mediated decay in mRNA quality control LO-04 Explain how the mTOR pathway globally controls translation during cell growth and in cancer cells LO-05 Diagram the pathway for the synthesis of miRNAs and discuss how miRNAs regulate the translation and stability of specific mRNAs. LO-06 Explain how an mRNA COVID-19 vaccine works LO-07 Discuss the how the frameshift mutations and mutations in introns can cause Duchenne muscular dystrophy IL: Genome Maintenance LO-01 Identify and describe the function of each of the following structures in the classical model of the DNA replication fork: (1) leading strand synthesis, (2) lagging strand synthesis, (3) DNA polymerase, (4) helicase, (5) single-stranded DNA binding protein, (6) DNA topoisomerase (7) primase, (8) ligase. and (9) sliding clamp; and (10) telomerase. LO-02 Compare and contrast the three different classes of DNA recombination: (1) homologous recombination, (2) site-specific recombination, and (3) transposition. Foundations Page 28 recombination, (2) site-specific recombination, and (3) transposition. LO-03

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Describe each of the major DNA repair pathways: (1) DNA mismatch repair; (2) base excision repair (BER); (3) nucleotide excision repair (NER); (4) translesion DNA synthesis; (5) double stranded break repair: homologous recombination-directed (HRD) repair & non-homologous end joining (NHEJ) repair; and (6) interstrand crosslink repair. LO-04 Explain the presentations and molecular etiologies of the following disorders involving DNA repair genes: xeroderma pigmentosum, Lynch Syndrome, ataxia telangiectasia, Werner syndrome, Bloom syndrome, Fanconi anemia, and BRCA1/BRCA2 dependent familial cancers. IL: Cellular Growth, Differentiation, and Adaptation LO-01 Describe tissue repair processes that occur after injury. Compare and contrast regeneration and connective tissue repair, and consider whether a tissue contains labile, stable or permanent cells. LO-02 Explain the importance of the extracellular matrix to normal cell growth, differentiation, and repair of injury. LO-03 Differentiate between hyperplasia, hypertrophy, atrophy, metaplasia and dysplasia; give causes, features and examples of each. Introduction to Pharmacokinetics LO-01 List the factors influencing passive diffusion of a molecule across a biological membrane. LO-02 Explain the basis for the relative influence of lipophilicity vs. size in influencing the diffusion of solutes across a lipid bilayer. LO-03 Explain the importance of distance in defining the rate of a diffusive process. LO-04 Explain the basis of "non-ionic diffusion" and "ion-trapping;" predict the effect of changes in pH on net diffusional flux of a weak acid or weak base between two compartments. LO-05 Describe the relationship between the molar concentration of osmotically active particles and the "osmotic pressure" of a solution; given knowledge of the osmotic concentration of opposing solutions, predict the direction of net water flux (i.e., osmosis). LO-06 List the diagnostic characteristics of carrier-mediated processes and explain how each can be used to distinguish passive (i.e., diffusion-based) transport from mediated transport. LO-07 Foundations Page 29

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LO-07 Describe the basis for the influence a competitive inhibitor has on the kinetics of transport of a competing substrate. Predict the effect the presence of a competitive inhibitor has on the kinetics of carrier mediated substrate transport. Distinguish between the predicted effects on transport kinetics of a competitive vs. a noncompetitive inhibitor. LO-08 Define the difference between facilitated “diffusion” and “active” transport; explain the criteria that are used to differentiate between these two processes. LO-09 Compare and contrast primary and secondary active transport. Discuss the characteristics that these two categories of mediated transport have in common and those that differentiate them. CBL: Marfan Syndrome LO-01 Identify the most common clinical findings in Marfan Syndrome LO-02 Discuss the inheritance pattern of Marfan Syndrome LO-03 Discuss the gene mutations in the fibrillin gene that are associated with Marfan Syndrome LO-04 Describe the most common locations in the aorta for aortic aneurysm and dissection in patients with Marfan Syndrome LO-05 Correlate the histology of the aorta with the pathogenesis of Marfan Syndrome Neoplasia LO-01 Define neoplasm and its related terms: tumor, cancer, oncology. LO-02 Given a tumor name, be able to determine the cell of origin and describe its behavior (benign vs. malignant). LO-03 Compare and contrast metaplasia, dysplasia and neoplasia. LO-04 Compare and contrast benign and malignant neoplasms in terms of differentiation, rate of growth, local invasion and metastatic potential. LO-05 Describe the morphologic features that characterize loss of differentiation (anaplasia). LO-06

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Foundations Page 30 LO-06 Describe the three pathways of metastasis and which routes are characteristic of different groups of neoplasm (carcinoma and sarcoma). LO-07 Summarize the impact of certain factors on the epidemiology of cancer: geography, environment, age, heredity, social factors. Give examples. LO-08 Compare and contrast the categories of genetic predisposition to cancer. LO-09 Describe the acquired conditions that predispose to cancer and give examples. LO-10 Define carcinogenesis. LO-11 Describe how mutations in the four classes of normal regulatory genes can lead to malignant transformation of a cell. LO-12 Describe the steps in chemical carcinogenesis. LO-13 Define direct and indirect chemical carcinogens. LO-14 Describe the mechanism whereby the three main classes of carcinogens cause cancer and give examples. LO-15 Summarize the range of effects of tumors on their host. LO-16 Define paraneoplastic syndrome and give an example. LO-17 Describe the microscopic features of that are used to grade a neoplasm. LO-18 Describe how neoplasms are staged and the significance of staging. CBL Molecular Genetics of Cancer LO-01 Describe the clinical presentation and diagnostic and therapeutic strategies for retinoblastoma and retinoblastoma-related metastatic osteogenic sarcoma. LO-02 Explain the function of the rb1 gene in cellular growth and proliferation and the role of the loss of heterozygosity in the etiology of retinoblastoma.

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Foundations Page 31 LO-03 Discuss the clinical presentation, diagnosis, and treatment of non-small cell lung cancer (nsclc) LO-04 Describe the how the mutations in the gene encoding the tyrosine kinase alk are associated with nsclc and are targeted for therapeutics. CBL Neurofibromatosis LO-01 Identify the most common clinical findings in Neurofibromatosis Types 1 & 2 LO-02 Discuss the inheritance pattern of Neurofibromatosis Types 1 & 2 LO-03 Discuss the gene mutations that are associated with Neurofibromatosis Types 1 & 2 LO-04 Describe the gene mutations that may portend different prognosis for patients with Neurofibromatosis Type 1. Neoplasia (Pathology Lab) LO-01 Recognize the cellular and architectural features of neoplasms and correlate with gross pathology findings. LO-02 Distinguish between benign and malignant neoplasms based on gross and microscopic features (interface with normal tissue, architecture, cellular features). LO-03 Distinguish different subtypes of benign or malignant neoplasms based on architecture and cellular features (e.g., adenoma, squamous cell carcinoma, adenocarcinoma, etc). LO-04 Distinguish benign or malignant neoplastic lesions from other types of lesions and normal (e.g., acute and chronic inflammatory lesions). LO-05 Begin associating certain cell types of neoplasia with certain organs as primary sites. CBL Breast Cancer LO-01 Discuss the risk factors, epidemiology, clinical presentation, diagnostic imaging, and surgical treatment for breast cancer

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LO-02 Foundations Page 32 LO-02 Explain how the presence of cell surface receptors for hormones and growth factors is used in the classification of breast cancer LO-03 Explain how genetic analysis is used in the diagnosis, prognosis, and therapeutic decisions for breast cancer LO-04 Correlate BRCA1 genemutations with dysregulation of gene expression LO-05 Discuss the use of qRT-PCR in breast in cancer prognosis & therapeutic decisions Cell Signaling and Role of Insulin in Regulation LO-01 Describe five key features of signaling pathways. LO-02 Identify the general structural features of a G protein-coupled receptor (GPCR) including its subunit composition. LO-03 Delineate the steps leading to activation/inhibition of adenylyl cyclase by GPCR. LO-04 Outline the general mechanism of signal transduction via G-proteins. LO-05 Discuss the signaling mechanism including the role of phospholipase C leading to the production of IP3, Ca2+, and DAG and the downstream effects of these second messengers including how IP3 causes Ca2+ release and how Ca2+ and DAG synergistically activate protein kinase C. LO-06 Define the major subtypes of alpha ( α )-and beta ( β )-adrenergic receptors, the second messenger systems to which they are linked and distinguish the changes in cyclic AMP with activation of alpha-1 and alpha-2 adrenergic receptors. LO-07 Compare the mechanisms by which cholera toxin and pertussis toxin cause overproduction of cyclic AMP. LO-08 Identify the general structural features of the insulin receptor, including its subunit composition and functional domains. LO-09 Delineate the steps leading to activation of the tyrosine kinase activity of the insulin receptor

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including the significance of interchain autophosphorylation of tyrosine residues in the insulin receptor. LO-10 Foundations Page 33 LO-10 Describe the mechanism by which insulin elicits mobilization of GLUT-4 glucose transporter protein to the plasma membrane in muscle and adipose tissue via IRS-1and PI-3K. Introduction to Ethical Thinking and Decision Making in Medicine LO-01 Identify common ethical conflicts in medicine. LO-02 Define the terms: autonomy, nonmaleficence, beneficence and justice; understanding their application in the context of specific case examples. LO-03 Identify the differences between principle-based, virtue-based, and casuistry ethical approaches. LO-04 Recognize the difference between ethics and the law. LO-05 List and apply the questions and components of an ethical deliberation. Molecular Therapeutics LO-01 Outline the basic strategies used in molecular therapeutics. LO-02 Describe the use of genetically engineered proteins in gene product augmentation therapy. LO-03 Discuss the advantages and disadvantages of the most common vector systems in gene replacement therapy. LO-04 Describe how CRISPR/Cas gene editing is used to correct point mutations and INDELS, how the technology has been applied to treatment of inherited human diseases. LO-05 Compare and contrast RNA/DNA interference, antisense oligonucleotides, and small molecule approaches for correction of aberrant gene expression associated with genetic diseases. LO-06 Discuss the treatment options for Duchenne muscular dystrophy, Huntingtin disease, and ADA severe combined immunodeficiency.

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Pharmacotherapeutics: Anti-Inflammatory Medications and Acetaminophen LO-01 Define pharmacotherapeutics. Foundations Page 34 LO-02 Describe the differences and similarities of aspirin vs. ibuprofen. LO-03 Compare and contrast naproxen and celecoxib. LO-04 Compare and contrast the use of NSAIDs and corticosteroids. LO-05 Describe the mechanism of hydroxychloroquine for arthritis and malaria. LO-06 Summarize the unwanted side effects of corticosteroids, aspirin, ibuprofen, indomethacin and celecoxib. LO-07 Describe what drug-drug interactions these anti-inflammatory medications may have if any. LO-08 Summarize the contraindications for the anti-inflammatory medications if any. LO-09 Describe the use of acetaminophen and whether it is considered an anti-inflammatory agent. Pharmacogenomics LO-01 Define pharmacogenetics and pharmacogenomics. LO-02 Describe specific inherited traits that influence drug metabolism in a clinically significant fashion. LO-03 Summarize the major mechanisms (i.e., metabolism, enzymes, receptors) through which genetic variation can alter responses to drugs. Give examples of each. LO-04 Describe the potential outcomes of genetic variations and the use of medications Metabolic Disorders: Diabetes Mellitus LO-01 Summarize the role of insulin in maintaining blood glucose homeostasis

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LO-02 Compare the pathogenesis and clinical features of Type 1 and Type 2 diabetes mellitus. LO-03 Explain the laboratory tests and criteria used in the diagnosis of diabetes mellitus Foundations Page 35 LO-04 Explain how metabolic syndrome is key to development of type 2 diabetes mellitus and the significance of metabolic susceptibility in this development. LO-05 Discuss the various analogs of insulin primarily used in the treatment of Type 1diabetes mellitus. Pharmacokinetics I: Absorption and Distribution LO-01 List the clinically used routes of drug administration. LO-02 Define and use appropriately the following terms: Absorption, Bioavailablity, Distribution, Apparent Volume of Distribution. LO-03 Explain how drugs can travel from the site of drug administration to the site of action. LO-04 Describe how pH affects the charge of weak acids and bases and the implications of charge for drug distribution. LO-05 Explain how plasma protein binding can affect drug distribution between plasma and tissues. LO-06 Describe the relationship between dose, plasma concentration, and apparent volume of distribution. LO-07 Explain how apparent volume of distribution differs between lipophilic and hydrophilic drugs. Pharmacokinetics II: Drug Metabolism LO-01 Highlight importance of biotransformation of chemicals. LO-02 Describe major biotransformation pathways for drugs. LO-03 Demonstrate competition for biotransformation between drugs. LO-04

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Evaluate factors that influence biotransformation of drugs. LO-05 Understand the difference between detoxification versus bioactivation. Foundations Page 36 Pharmacokinetics III: Drug Elimination LO-01 Understand how drug movement between pharmacokinetic compartments affects plasma concentration over time. LO-02 Understand how drug movement between pharmacokinetic compartments affects the rate of drug elimination. LO-03 Define and calculate the following pharmacokinetic parameters: a.Clearance, b. Elimination Half life, c. Rate constant LO-04 Use clearance, bioavailability, and/or volume of distribution to calculate: a. Loading dose to achieve a desired steady-state plasma concentration b. Maintenance dose to ensure a patient remains at a steady-state plasma concentration. CBL: Diabetes Type 1 LO-01 Summarize the role of insulin in maintaining blood glucose homeostasis. LO-02 Compare the pathogenesis and clinical features of Type 1 and Type 2 diabetes mellitus. LO-03 Explain the laboratory tests and criteria used in the diagnosis of diabetes mellitus. LO-04 Discuss the various analogs of insulin primarily used in the treatment of Type 1diabetes mellitus. LO-05 Apply and integrate basic immunology concepts to a clinical scenario. IL: Tolerance and Autoimmunity LO-01 Give the three defining properties needed to establish the presence of an autoimmune disease. LO-02 List and explain the general features that characterize autoimmune diseases. LO-03

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Explain the difference between central and peripheral tolerance, and describe the basic mechanisms by which immunological tolerance against “self” is established, including clonal deletion, anergy, and the activity of regulatory T cells. LO-04 Explain how genetics and environment both contribute to the development of autoimmunity. Foundations Page 37 Explain how genetics and environment both contribute to the development of autoimmunity. LO-05 Describe the proposed mechanisms by which tolerance can be broken to produce autoimmunity, including bystander activation, molecular mimicry, release of sequestered antigens, and superantigen-mediated disease induction. LO-06 Describe the clinical features of systemic lupus erythematosus (SLE), including common abnormalities of the facial skin and renal glomeruli. LO-07 Know the common autoantibody tests for SLE, including two autoantibodies which are virtually diagnostic for this disease when present. LO-08 Identify four non-genetic factors that can impact SLE. LO-09 Describe three immunologic factors that contribute to the pathogenesis in SLE, including abnormalities of T-cells, type II hypersensitivity and type III hypersensitivity. LO-10 In addition to serologic testing, identify tissue biopsy (skin, kidney) as important laboratory tests in the diagnostic workup of SLE. LO-11 For Type I diabetes, list the main cellular targets and common clinical manifestations. IL: Hypersensitivity Reactions LO-01 Explain what is meant by the terms “immunopathology”, “hypersensitivity”, and “allergy”. LO-02 Explain the basic immunologic pathways that are active in each of the four types of hypersensitivity reactions. LO-03 Contrast the roles of antibody molecules between Type I, II, and III reactions. LO-04 Explain the role of mast cells in Type I reactions and the key inflammatory mediators they produce.

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LO-05 For the following conditions, list the type of hypersensitivity reaction involved, and pathology observed: urticaria, asthma, anaphylaxis, systemic lupus erythematosus LO-06 Review the steps which lead to the formation of a granuloma, and provide examples of granulomatous diseases. Foundations Page 38 IL: Amyloidosis LO-01 Define amyloidosis as a heterogeneous group of inherited and inflammatory disorders that lead to tissue damage and functional compromise due to accumulation of fibrillary proteins. LO-02 Describe the physical and chemical properties of amyloid proteins and their unique structural arrangement that leads to special staining characteristics with Congo Red dye. LO-03 Recognize the appearance of amyloid protein in histologic sections from affected organs (including interpretation of Congo Red stain) and by ultrastructural examination (electron microscopy). LO-04 Understand how amyloidosis is classified in terms of systemic, hereditary and localized forms. LO-05 Describe the features of primary amyloidosis, including the specific amyloid protein most commonly involved, and recognize the underlying etiology/group of diseases associated with this disorder. LO-06 Describe the features of reactive systemic amyloidosis, including the specific amyloid protein involved, and list the most common underlying diseases associated with this disorder. LO-07 Identify the most common types of amyloid proteins associated with hemodialysis-associated amyloidosis, Familial Mediterranean fever, Alzheimer disease, medullary carcinoma of the thyroid, Islets of Langerhans (type 2 diabetes), and amyloid of aging. LO-08 Recognize LECT2 amyloid as a cause of amyloidosis and renal failure with high incidence in Hispanic patients. LO-09 Describe the clinical manifestations of amyloidosis, including manifestations in kidney, heart, gastrointestinal tract and blood vessels. IL: Diabetes: Chronic Management, Screening Exams and Emerging Technology LO-01 List the annual screening examinations and testing for patients with diagnosed diabetes.

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LO-02 Describe the underlying chronic conditions for which these tests evaluate. LO-03 Describe recent advances using technology in management of patients with diabetes. Foundations Page 39 TL: Immunology and Inflammation LO-01 Explain the major mechanisms of innate immunity and be able to explain how these pathways can contribute to pathology. LO-02 Explain how adaptive immune responses are generated for B and T cells. Describe the effector mechanisms of lymphocytes, how they can contribute to pathology, and be able to recognize their presence in microscopic sections. LO-03 Contrast the general time course and transition of events characterizing acute and chronic inflammation. Recognize these features in cardiac tissue following myocardial infarction. LO-04 Explain the cellular sources, target tissues, and main roles of key inflammatory mediators covered in the basic immunology, acute inflammation, and chronic inflammation lectures. LO-05 Explain the molecular and cellular events that underlie each of the four types of hypersensitivity. Recognize the typical clinical presentations and expected histologic findings in affected tissues of patients with hypersensitivity reactions, including organ transplant rejection. LO-06 Explain the processes by which immunological tolerance to “self” is produced and maintained, and factors that can lead to a loss of tolerance. Provide the target antigens and tissues for common autoimmune diseases, and explain how immune attack of those organs produces the respective clinical pictures for these diseases. CBL: Diabetes & Metabolic Disease LO-01 Explain what is meant by “Insulin Resistance” in Type 2 Diabetes Mellitus (DM). LO-02 Compare and contrast the pathophysiology of Type 1 and Type 2 Diabetes Mellitus. LO-03 Compare and contrast the treatment and long term management of Type 1 and Type 2 DM.

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LO-04 Explain the pathophysiology of the clinical symptoms of polydipsia and polyuria in DM. LO-05 Explain what is meant by the diagnosis of Type 1.5 DM LO-06 Explain the role of C-peptide and GAD antibodies in the diagnosis of hyperglycemia. LO-07 Explain the mechanism of action, clinical indications for administration, and complications of Foundations Page 40 Explain the mechanism of action, clinical indications for administration, and complications of Metformin, Glipizide, and Insulin. CBL: Lupus LO-01 Apply your knowledge of the disciplines from Foundations Block to cases of SLE, including general anatomy, histology, pathology, biochemistry, genetics, and clinical evaluation. Therapy Decisions 101 LO-01 Become familiar with the vocabulary terms. LO-02 Identify the many different goals of therapeutic interventions. LO-03 Identify the factors that patients and physicians must consider prior to choosing a therapy. LO-04 Understand the study designs used to evaluate therapeutic interventions and be familiar with the phases of FDA drug trials. LO-05 Understand how bias affects study results and how elements of study design diminish those effects. LO-06 Understand common measures of therapeutic benefit and given a study, be able to construct a 2 x 2 table to calculate: a. NNT/NNH b. RR/OR c. Relative Risk Reduction d. Absolute Risk Reduction LO-07 Demonstrate a basic understanding of effect precision in terms of a p value and confidence interval and understand their impact on study result validity. LO-08

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Understand the concept of hypothesis testing and the null hypothesis/value. LO-09 Demonstrate the ability to interpret statistical significance based on a p-value or confidence interval. LO-10 Understand limitations of therapeutic trials and how they may apply to your patients. Therapy Decisions 102 - Advanced Study Designs and Systematic Reviews LO-01 Understand the vocabulary terms provided. Foundations Page 41 LO-02 Understand bias as it affects the results of clinical research. LO-03 Understand the different types of statistical error. LO-04 Outline the fundamental process by which a systematic review and meta-analysis are constructed and published. LO-05 Describe why systematic reviews and meta-analyses might be useful in clinical decision-making. LO-06 Characterize the possible biases that are potentially present with systematic reviews and meta analyses. TL: Pharmacology LO-01 Explain the difference between affinity, potency and efficacy. LO-02 Discuss how an antagonist prevents the effects of an agonist and the differences between competitive and non-competitive antagonists. LO-03 Describe basic characteristics of the GPCRs, Ligand gated ion channels, Kinase receptors and nuclear receptors (for example ligand-gated ion channels allow the passage of ions, produce rapid responses, are multimeric proteins … .) LO-04 Calculate the therapeutic index of a drug. LO-05 Explain the differences between phase I and phase II drug metabolism and how alterations in

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phase I and phase II enzyme levels can alter medication therapeutic and/or side effects. LO-06 Illustrate the effects of pH on the ability of weak acids and bases to cross membranes. (Describe the relationship between apparent volume of distribution, dose and plasma drug concentration). LO-07 Explain how volume of distribution and clearance affect drug half-life. Know how to use the equations for clearance, distribution, half-life, maintenance dose and loading dose. LO-08 Review medications use for inflammation. Clinical Decision Rules and Practice Guidelines Foundations Page 42 LO-01 Become familiar with the vocabulary terms. LO-02 Summarize the fundamental characteristics of Clinical Decision Rules (CDR) and Clinical Practice Guidelines (CPG). LO-03 Understand how Clinical Decision Rules (CDR) are created and how clinicians may choose to use them. LO-04 Be familiar with the common types of recommendations given by widely adapted CPGs such as the GRADE working group. LO-05 Demonstrate an understanding of the benefits and risks of using CPGs, CDRs in clinical decision making. LO-06 Identify the limitations of using CDRs and CPGs on individual patients.

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Foundations Page 43

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Foundations - Learning Objectives for Final Exam

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