General pathology and physiopathology

A.Y. 2019/2020
Overall hours
Learning objectives
The course aims at providing knowledge in:
i) molecular mechanisms of damage at the cellular, tissue and organismic level,
ii) subcellular, cellular, tissue and organismic responses to damage,
iii) integration of the said elements towards the understanding of selected topics in physiopathology, iv) state-of-the-art in genomic medicine and precision medicine.
Expected learning outcomes
a) know the mechanisms of damage and of the responses to damage,
b) know the principles and the pathological implications of acute and chronic inflammation,
c) know the biological and molecular bases of cancer and the molecular rational of anti-cancer therapies,
d) possess integrated knowledge of physiopathology in selected topics including coagulation disorders, cancer, liver diseases, kidney diseases, endocrine diseases, bowel inflammatory diseases and neurodegenerations,
e) are capable of interpreting molecular profiles in genomic medicine.
Course syllabus and organization

Single session

Course syllabus
Cellular damage, biochemical and molecular mechanisms and functional implications
Concepts of etiology and pathogenesis. Reversible and irreversible cellular damage. Causes of cellular damage. Morphological aspects of damage and necrosis.
Mechanisms (biological, biochemical, molecular) of cellular damage.
Cellular responses and/or adaptation to stress and to damage.
Subcellular responses. Intracellular accumulations. Calcifications. Cellular aging.
Hypoxia, ischemia, hypoperfusion.
Apoptosis: physiology and pathology. Molecular mechanisms, morphological aspects.
Environment and nutrition as cause of damage.

General features of acute and chronic inflammation.
Acute inflammation: vascular modifications, cellular events e molecular mechanisms.
The chemistry of acute inflammation (amines, NO, complement, cytokines e chemokines). Correlation between biochemical features and morphological and functional aspects.
Inflammation as a systemic event: acute phase proteins, fever, other symptoms of acute phase.
Chronic inflammation: morphological aspects, functional aspects, molecular mechanisms.
Tissue repair and fibrosis.
Diseases characterized by marked inflammatory and degenerative aspects. Amyloidosis.

General Oncology
Cancer: definition, morphology, benign and malignant tumors.
Cancer epidemiology and risk factors. Genetics and inheritance in cancer.
Carcinogenesis: chemical, physical biological.
Stem cell theory of cancer.
Paraneoplastic syndromes.
Normal and cancer angiogenesis.
Cell autonomous and non-cell-autonomous mechanisms of cancer.

Molecular Oncology
The concepts of oncogenes (dominant) and tumor suppressor gene (recessive). Multistep carcinogenesis.
Molecular bases of tumorigenesis: alterations of growth factors and growth factor receptors.
Molecular bases of tumorigenesis: mechanisms of receptor attenuation and their subversion.
Molecular bases of tumorigenesis: subversion of adhesion molecules.
Molecular bases of tumorigenesis: alterations of the intracellular mechanisms of signal transduction.
Molecular bases of tumorigenesis: protein:protein interactions, significance and alterations.
Molecular bases of tumorigenesis: cell cycle, checkpoints and their alterations.
Molecular bases of tumorigenesis: DNA damage response and its subversion.
Chromosomic translocations and fusion proteins: Burkitt's lymphoma, chronic myeloid leukemia, acute leukemias.
Molecular and rational basis of therapy. Chemoprevention.

Senescence and aging
Reactive Oxygen Species (ROS), physiology and physio-pathology.
Cellular senescence: telomeres e telomerase, ROS, mitochondrial DNA.
Organismal aging. Theories of aging.

The human genome and the genomic medicine
The human genome and the model genomes. Relevance for BioMedicine.
Genomic databases in BioMedicine.
Molecular Medicine and diagnostic and therapeutic implications.
Technologies in BioMedicine in the post-genomic era.
Ethical implications. The physician in the post-genomic era.
Genomics and drug discovery.

Selected topics in physiopathology
Coagulations and diseases of coagulation.
Liver diseases (Acute and chronic hepatitis, liver cirrhosis).
Bowel Inflammatory diseases.
Endocrine pathologies (diabetes, thyroid diseases)
Breast carcinoma
Colon carcinoma
Prerequisites for admission
Based on the knowledge acquired in the "Biology and Genetics" and "Chemistry and Biochemistry" courses, students are expected to possess knowledge of the principles of cellular and subcellular organization, of the structure and function of biological macromolecules, of the molecular biology of the cell, of genetics, enzymology, bioenergetics and metabolic circuitries.
Teaching methods
The course comprises 12 CFU.
Of these, 9 are provided during the second semester of the second year of the master degree course. At the end of this phase, the students are admitted to the exam.
This part of the course is further subdivided in 8 CFU of "frontal" teaching (see the detailed program below) and 1 CFU of laboratory activity ("Attività Professionalizzanti"). Frontal teaching is based on the use of slides in Power Point. The slides are uploaded onto the Ariel website. For these latter activities, students are grouped into groups of 3 students, each assigned to a tutor, and spend three consecutive afternoons in the lab, participating "hands-on" on a mini-project in genomic medicine. These activities are designed to familiarize the students with the basic and translational research activities behind the concepts and the progresses in genomic and precision medicine.

Three CFUs are provided during the 5th year as a part of the integrated Clinical Medicine course (D53-153). These CFUs take up topics related to the pathological bases of diseases that represent an integral part of the General Pathology and Fisio-Pathology course of the 2nd year and, as such, are not object of additional examination. As a whole, these 3 CFUs represent a "Back to Basics" section that aims at highlighting the importance of discussing the different aspects and multifaceted implications of basic science for clinical medicine, in the perspective of a better patient care. The goal is to familiarize the students with cutting edge genomic and molecular knowledge and demonstrate, through the discussion of specific clinical cases and disease models, the relevance of basic research findings to the clinico-prognostic and therapeutic improvements in the clinical practice.
In addition to frontal teaching, the course also takes the form of teacher-guided lectures and seminars delivered by groups of 2/3 students, which represents an effective strategy to encourage active learning and communication, and develop critical-thinking and decision-making in relation to clinical problems.
Teaching Resources
- Patologia Generale. Robbins e Cotran vol 1: Le basi patologiche delle malattie. VIII edizione. Elsevier
- Patologia Generale e Fisiopatologia generale - G.M. Pontieri. VI edizione. Piccin.
Assessment methods and Criteria
The exam consists in a single oral examination. There are no intermediate tests.
The oral examination aims at evaluating the ability of the student to express him/herself with clarity, scientific rigor, and appropriate language on the topics of the course: a) molecular mechanisms of damage at the cellular, tissue and organismic level, b) subcellular, cellular, tissue and organismic responses to damage, c) integration of the said elements towards the understanding of selected topics in physiopathology, d) state-of-the-art in genomic medicine and precision medicine.
The oral exam last, on the average, 30-40 minutes and consists of the discussion of 3-4 general topics, selected among the general issues of cellular and tissue damage and organismal responses, acute and chronic inflammation, oncology, genomic medicine, and physiopathology. Within the discussion of each topics, there is further "ad hoc" deepening into single aspects of the problems.
The outcome of the exam is expressed in thirtieths.
Informal teaching: 16 hours
Lessons: 96 hours
Gruppo 1
Professor: Di Fiore Pier Paolo
Gruppo 2
Professor: Pelicci Pier Giuseppe
Gruppo 3
Professor: Pece Salvatore
Gruppo 4
Professor: Scita Giorgio
Gruppo 5
Professor: Alcalay Myriam
Gruppo 6
Professor: Chiaramonte Raffaella
Gruppo 7
Professor: Polo Simona Laura Anna
Gruppo 8
Professor: Dellino Gaetano Ivan
Gruppo 9
Professor: Malabarba Maria Grazia