Unit GENERAL PATHOLOGY AND PHYSIOPATHOLOGY

GENERAL PATHOLOGY AND PHYSIOPATHOLOGY - MOD. 1

Code	A000348
Location	PERUGIA
CFU	6
Learning activities	Caratterizzante
Area	Patologia generale e molecolare, immunopatologia, fisiopatologia generale, microbiologia e parassitologia
Academic discipline	MED/04
Type of study-unit	Obbligatorio (Required)

Cognomi A-L

CFU

6

Teacher

Andrea Bartoli

Teachers

• Andrea Bartoli

Hours

• 75 ore - Andrea Bartoli

Language of instruction

Italian

Contents

Definitions
Molecular pathology
Causes of disease
Intrinsic causes
Extrinsic cause

Reference texts

Pontieri, Russo, Frati.
Patologia Generale
Piccin Ed.

Robbins Kumar Cotran
The pathologic basis of disease
Elsevier

Educational objectives

Acquisition of the basics on the causes of disease, with the molecular mechanisms triggered by them

Prerequisites

Physics, chemistry and cell biology. Basic genetics. Biochemistry of nucleic acids, proteins and lipids.
Histology. Human anatomy. Elements of Immunology

Teaching methods

Lectures, class discussions, visualization and commentary of images and laboratory procedures. Viewing movies. Work in a group. Inverted classes. Peer to peer teaching

Learning verification modality

Itinere verification in the classroom

Extended program

-Concept of disease: state of health and disease. Etiology and Pathogenesis concept.


I - CAUSES OF DISEASE


A) DISEASES FROM ENVIRONMENTAL AGENTS: PHYSICAL AND CHEMICAL.

Low temperature pathologies: Freezing.
High temperature pathologies: burns,
Non ionizing and ionizing radiation pathologies.
Electrical and electromagnetic energy pathologies (outline).
Mechanical and gravitational energy pathologies (outline).
Main chemical agents responsible for diseases and causes of cell damage (outline).

B) EPIGENETIC, GENETIC AND CHROMOSOMIC PATHOLOGY

- INSTRUMENTAL GENE ANALYSIS IN THE DIAGNOSIS OF HUMAN DISEASES (NOTES)

- EPIGENETICS
Epigenetic regulation of gene functionality and main epigenetic modifications. Epigenetic-environment interactions. Epigenetics and human pathology.

- DNA MUTATION
Mutations in regulatory and coding regions and their functional consequences.

- DNA REPAIR
Main molecular repair mechanisms and molecular pathology of DNA repair. Pathology of "mismatch repair". Lynch syndromes and hereditary colorectal cancer. Pathology of the "excision repair". Xeroderma pigmentosum and telangiectasic ataxia. Oncological and non-oncological consequences of altering DNA repair, connection with cellular and organism senescence.

- RNA PATHOLOGIES
Consequences on RNA of gene mutations. Splicing changes. Non-coding RNAs and their alterations in the pathogenesis of human pathologies: basic concepts


- MONOGENIC DISEASES
PROTEIN PATHOLOGY: FROM MUTATION TO DISEASE

A) Complexity of monogenic diseases: genetic heterogeneity, allelic heterogeneity, interaction between genes and their products, gene-environment interactions, germ and somatic mutations.

B) MUTATION OF ENZYMATIC PROTEINS AND FUNCTIONAL INTRACELLULAR PROTEINS
- Lysosomal enzyme deficiency (thesaurismosis) with consequent intracellular accumulation: Wolman's disease, lipidosis, gangliosidosis, mucopolysaccharidosis and glycogenosis.
- Hereditary pathologies of amino acid metabolism. (Phenylketonuria).
- Hemoglobinopathies and hemoglobinopenias (thalassemias, sickle cell)
- Deficiency of homeostatic proteins: G-6-PD
- Proteins that regulate proliferation (see oncology): Neurofibromatosis

C) PATHOLOGY OF THE CELL MEMBRANE: MUTATION OF RECEPTORAL PROTEINS AND TRANSPORT SYSTEMS
- Cystic fibrosis,
- Familial hypercholesterolaemia
- Achondroplasia
- Hemochromatosis and iron metabolism. (Hemosiderosis)

D) PATHOLOGY OF CELL MEMBRANE: MUTATION OF STRUCTURAL PROTEINS AND CYTO-SKELETON
- Hereditary spherocytosis and elliptocytosis,
- Muscular dystrophies

E) MUTATION OF EXTRA-CELL FUNCTIONAL PROTEINS
- Hereditary coagulation pathology: hemophilia, von Willebrand disease, hypercoagulable states

F) CONNECTIVE PATHOLOGY: MUTATION OF EXTRACELLULAR STRUCTURAL PROTEINS
- Hereditary collagen pathology (S. of Ehlers Danlos)
- Hereditary pathology of elastic fibers (S. di Marfan)

G) MONOGENIC DISEASES WITH NON-MENDELIAN HERITAGE
Repeated Triplet Diseases: Fragile X Syndrome. Huntington's disease
Mitochondrial DNA mutations. Pathologies inherited by imprinting

CHROMOSOME PATHOLOGY: NUMERICAL AND STRUCTURAL ALTERATIONS
Trisomies and monosomies of autosomes and sex chromosomes: Down syndrome. Turner syndrome, Klinefelter syndrome.

EMBRYOPATHIES AND FETOPATHIES
Principles of teratogenesis. Physical, chemical and infectious teratogenes

COMPLEX DISEASES AND MULTIFACTORIAL AND POLYGENIC HERITAGE
Genetic, epigenetic and environmental mechanisms

Cognomi M-Z

CFU

6

Teacher

Francesco Grignani

Teachers

• Francesco Grignani

Hours

• 75 ore - Francesco Grignani

Language of instruction

Italian

Contents

Definitions
Molecular pathology
Causes of disease
Intrinsic causes
Extrinsic cause

Reference texts

Pontieri, Russo, Frati.
Patologia Generale
Piccin Ed.

Robbins Kumar Cotran
The pathologic basis of disease
Elsevier

Educational objectives

Acquisition of the basics on the causes of disease, with the molecular mechanisms triggered by them

Prerequisites

Physics, chemistry and cell biology. Basic genetics. Biochemistry of nucleic acids, proteins and lipids.
Histology. Human anatomy. Elements of Immunology

Teaching methods

Lectures, class discussions, visualization and commentary of images and laboratory procedures. Viewing movies. Work in a group. Inverted classes. Peer to peer teaching

Learning verification modality

Itinere verification in the classroom

Extended program

-Concept of disease: state of health and disease. Etiology and Pathogenesis concept.


I - CAUSES OF DISEASE


A) DISEASES FROM ENVIRONMENTAL AGENTS: PHYSICAL AND CHEMICAL.

Low temperature pathologies: Freezing.
High temperature pathologies: burns,
Non ionizing and ionizing radiation pathologies.
Electrical and electromagnetic energy pathologies (outline).
Mechanical and gravitational energy pathologies (outline).
Main chemical agents responsible for diseases and causes of cell damage (outline).

B) EPIGENETIC, GENETIC AND CHROMOSOMIC PATHOLOGY

- INSTRUMENTAL GENE ANALYSIS IN THE DIAGNOSIS OF HUMAN DISEASES (NOTES)

- EPIGENETICS
Epigenetic regulation of gene functionality and main epigenetic modifications. Epigenetic-environment interactions. Epigenetics and human pathology.

- DNA MUTATION
Mutations in regulatory and coding regions and their functional consequences.

- DNA REPAIR
Main molecular repair mechanisms and molecular pathology of DNA repair. Pathology of "mismatch repair". Lynch syndromes and hereditary colorectal cancer. Pathology of the "excision repair". Xeroderma pigmentosum and telangiectasic ataxia. Oncological and non-oncological consequences of altering DNA repair, connection with cellular and organism senescence.

- RNA PATHOLOGIES
Consequences on RNA of gene mutations. Splicing changes. Non-coding RNAs and their alterations in the pathogenesis of human pathologies: basic concepts


- MONOGENIC DISEASES
PROTEIN PATHOLOGY: FROM MUTATION TO DISEASE

A) Complexity of monogenic diseases: genetic heterogeneity, allelic heterogeneity, interaction between genes and their products, gene-environment interactions, germ and somatic mutations.

B) MUTATION OF ENZYMATIC PROTEINS AND FUNCTIONAL INTRACELLULAR PROTEINS
- Lysosomal enzyme deficiency (thesaurismosis) with consequent intracellular accumulation: Wolman's disease, lipidosis, gangliosidosis, mucopolysaccharidosis and glycogenosis.
- Hereditary pathologies of amino acid metabolism. (Phenylketonuria).
- Hemoglobinopathies and hemoglobinopenias (thalassemias, sickle cell)
- Deficiency of homeostatic proteins: G-6-PD
- Proteins that regulate proliferation (see oncology): Neurofibromatosis

C) PATHOLOGY OF THE CELL MEMBRANE: MUTATION OF RECEPTORAL PROTEINS AND TRANSPORT SYSTEMS
- Cystic fibrosis,
- Familial hypercholesterolaemia
- Achondroplasia
- Hemochromatosis and iron metabolism. (Hemosiderosis)

D) PATHOLOGY OF CELL MEMBRANE: MUTATION OF STRUCTURAL PROTEINS AND CYTO-SKELETON
- Hereditary spherocytosis and elliptocytosis,
- Muscular dystrophies

E) MUTATION OF EXTRA-CELL FUNCTIONAL PROTEINS
- Hereditary coagulation pathology: hemophilia, von Willebrand disease, hypercoagulable states

F) CONNECTIVE PATHOLOGY: MUTATION OF EXTRACELLULAR STRUCTURAL PROTEINS
- Hereditary collagen pathology (S. of Ehlers Danlos)
- Hereditary pathology of elastic fibers (S. di Marfan)

G) MONOGENIC DISEASES WITH NON-MENDELIAN HERITAGE
Repeated Triplet Diseases: Fragile X Syndrome. Huntington's disease
Mitochondrial DNA mutations. Pathologies inherited by imprinting

CHROMOSOME PATHOLOGY: NUMERICAL AND STRUCTURAL ALTERATIONS
Trisomies and monosomies of autosomes and sex chromosomes: Down syndrome. Turner syndrome, Klinefelter syndrome.

EMBRYOPATHIES AND FETOPATHIES
Principles of teratogenesis. Physical, chemical and infectious teratogenes

COMPLEX DISEASES AND MULTIFACTORIAL AND POLYGENIC HERITAGE
Genetic, epigenetic and environmental mechanisms

GENERAL PATHOLOGY AND PHYSIOPATHOLOGY - MOD. 2

Code	A000349
Location	PERUGIA
CFU	1
Learning activities	Caratterizzante
Area	Patologia generale e molecolare, immunopatologia, fisiopatologia generale, microbiologia e parassitologia
Academic discipline	MED/04
Type of study-unit	Obbligatorio (Required)

Cognomi A-L

CFU

1

Teacher

Giuseppe Servillo

Teachers

• Giuseppe Servillo

Hours

• 12.5 ore - Giuseppe Servillo

Language of instruction

Italian

Contents

Molecular basis of extrinsic causes of pathology in human.

Reference texts

-PONTIERI FRATI, RUSSO: - Due Volumi- Patologia Generale. Fisiopatologia Generale Ed. PICCIN
-DIANZANI : Istituzioni di Patologia Generale Ed. UTET

Educational objectives

Module 2 of General Pathology is part of the teaching of General Pathology, the Degree in Medicine and Surgery, who studies the causes (etiology) and pathological phenomena at the molecular and cellular disease than the biology and physiology of cell. The course intends to acquire knowledge about the basic mechanisms underlying the most common diseases in humans and the cell response to changes in the external environment. The main objective of the course is to acquire knowledge about:
• intrinsic molecular pathology
• causes physical, chemical and biological disease
• molecular mechanisms of cell death
The oral examination and optional seminars are tools to assess the degree of learning and the ability to communicate and explain, in a simple, yet rigorous, immediate and thorough knowledge gained. The skills acquired in the study of this discipline allows the student to achieve a broad overview of the relationship between the human genome, the environment and the development of diseases and allows to obtain the means to have a clear picture of the causes of pathologies and their specific mechanism of occurrence and development and general pathophysiology of the most common diseases in order to propose behaviors and appropriate treatment as a future Medical Doctor.

Prerequisites

The acquisitionof of an in deep knowledge of main topics in the course of General Pathology, requires relevant knowledge on Biology and Genetics, Biochemistry and Physiology. The skill so btained in these disciplines are essential so that students can understand the concepts of etiopathology of Molecular and Cellular Pathology and Pathophysiology of organs. The student so well prepared in teaching the course will draw a considerable profit.

Teaching methods

To the students are given lectures. The lectures deal with the part of the program of the course of study on the extrinsic causes of disease, with greater reference to the Environmental Pathology, issues of common disorders, that the future physician will face in the course of his profession. Each lesson has a duration of two hours that is given to the specific topic, relating it to others already exposed, to allow the student to have a broad vision of the topics covered. Students are proposed to conduct, at its option, seminars about the arguments in class. The seminars were held in groups of two or three people. The seminars were held in groups of two or three students in the presence of the other students in the course. To this end, the teacher provides students with bibliographical material in English concerning the subject, the subject of the seminar will be presented using computer media (Power-Point and / or similar).

Other information

Learning verification modality

The student evaluation consists of an oral exam at the end of the course lessons. The assessment of the preparation of the student lasts an average of thirty minutes depending on the degree of knowledge of the topics covered and the presentation skills of the student. The test consists of three questions regarding the discipline studied related to: molecular and cellular pathology of the intrinsic and extrinsic causes of disease; cellular pathology and molecular oncology and inflammation; general pathophysiology of organs. The questions are administered by different teachers to ensure maximum consistency and objectivity of evaluation. The oral examination is essential for the assessment of the knowledge acquired by the students, exhibition of his skills and mastery of the subject studied with particular referenceto the ability to link between different topics.

Extended program

Extrinsic Causes of Disease -Physical agents. Non ionizing and ionizing radiation. Low and high temperature: freezing and burn. Electric and electromagnetic energy. -Chemical and Environmental agents. Environment pollution, Drugs. -Alimentary causes. Vitamins: A, D, E, K, B and C group. -Free Radical: Oxidative stress. -Causes of Embryopathy and Fetopathy: physical, infective, endocrine and toxic.

Cognomi M-Z

CFU

1

Teacher

Francesco Grignani

Teachers

• Francesco Grignani

Hours

• 12.5 ore - Francesco Grignani

Language of instruction

Italian

Contents

Elementary lesions of the cell. Ischemia
Cell death: necrosis, apoptosis, autophagy.

Reference texts

Pontieri, Russo, Frati.
Patologia Generale
Piccin Ed.

Robbins Kumar Cotran
The pathologic basis of disease
Elsevier

Educational objectives

Knowledge of the elementary lesions of the cell and of the damages that lead to the different modalities of cell death

Prerequisites

Physics, chemistry and cell biology. Basic genetics. Biochemistry of nucleic acids, proteins and lipids.
Histology. Human anatomy. Elements of Immunology

Teaching methods

Lectures, class discussions, visualization and commentary of images and laboratory procedures. Viewing movies. Work in a group. Inverted classes. Peer to peer teaching. Online teaching

Learning verification modality

Itinere verification in the classroom

Extended program

II - CELLULAR AND CONNECTIVAL PATHOLOGY

ELEMENTARY INJURY OF THE CELL. Mechanisms of cellular damage and consequent elementary pathology of the nucleus, mitochondrion, endoplasmic reticulum, lysosome, cytoskeleton, peroxisomes, Golgi apparatus and cell membrane.
Pathogenic effects of free radicals and oxidative stress.
ATP deficiency; Mitochondrial damage Alteration of calcium flows; Membrane damage; Damage from impaired protein folding.
Ischemia and ischemia and reperfusion

CELLULAR DEATH.

- NECROSIS Types of necrosis, coagulative and colliquative. Gangrene. The outcomes of the necrotic process.

- APOPTOSIS: definition and morphological and cellular phenomena. Apoptosis in physiology and pathology. Stimuli activating apoptosis. Receptor and mitochondrial pathways for the activation of apoptosis. Molecular regulation of apoptotic death, the Bcl-2 and p53 family. Caspases and their molecular targets. Apoptosis and cancer.

- AUTOPHAGY, nephroptosis, entosis

GENERAL PATHOLOGY AND PATHOPHYSIOLOGY - MOD. 3

Code	GP004612
Location	PERUGIA
CFU	1
Learning activities	Caratterizzante
Area	Patologia generale e molecolare, immunopatologia, fisiopatologia generale, microbiologia e parassitologia
Academic discipline	MED/04
Type of study-unit	Obbligatorio (Required)

Cognomi M-Z

CFU

1

Teacher

Francesco Grignani

Teachers

• Francesco Grignani

Hours

• 12.5 ore - Francesco Grignani

Language of instruction

Italian

Contents

Regressive processes and cellular and tissue adaptation mechanisms.
Senescence and aging.
Repair and stem cells

Reference texts

Pontieri, Russo, Frati.
Patologia Generale
Piccin Ed.

Robbins Kumar Cotran
The pathologic basis of disease
Elsevier

Educational objectives

Knowledge of molecular and cellular mechanisms of cellular regressive processes and adaptation mechanisms of cells and tissues. Aging and aging mechanisms. Tissue repair mode. Types of functions and usefulness of stem cells

Prerequisites

Physics, chemistry and cell biology. Basic genetics. Biochemistry of nucleic acids, proteins and lipids.
Histology. Human anatomy. Elements of Immunology

Teaching methods

Lectures, class discussions, visualization and commentary of images and laboratory procedures. Viewing movies. Work in a group. Inverted classes. Peer to peer teaching

Learning verification modality

Itinere verification in the classroom

Extended program

REGRESSIVE CELLULAR PROCESSES. Intracellular degenerations. Fatty. Vacuolar and hydropic degeneration. Turbid swelling. Hyaline and mucous degeneration.

EXTRACELLULAR REGRESSIVE PROCESSES. Amyloidosis, hyaline, fibrinoid and mucous degeneration. Pathology of the extracellular matrix components: fibrosis, sclerosis. Cirrhosis.

PATHOLOGY AND PATHOPHYSIOLOGY OF THE EXTRACELLULAR MATRIX. Structure, biosynthesis and degradation of the components of the matrix and its alterations. Cell-matrix interactions and their alterations.

CELLULAR AND TISSUE ADAPTIVE PHENOMENA

HYPOTHROPHY AND ATROPHY
PROGRESSIVE PROCESSES: HYPERTROPHY AND HYPERPLASIA

SENESCENCE AND AGING. Senescence theories. Cell senescence in intermitotic and post-mitotic cells. Molecular level senescence analysis. Re plicative and stress senescence. Aging of the organism. Aging pathology.

III - REPAIR AND REGENERATION

Outcomes of cell damage and inflammatory processes.
The reparative processes and the granulation tissue.
Wound repair
Tissue regeneration.
Stem cells: definition, types, potential and regenerative medicine

Cognomi A-L

CFU

1

Teacher

Andrea Bartoli

Teachers

• Andrea Bartoli

Hours

• 12.5 ore - Andrea Bartoli

Language of instruction

Italian

Contents

Regressive processes and cellular and tissue adaptation mechanisms.
Senescence and aging.
Repair and stem cells

Reference texts

Pontieri, Russo, Frati.
Patologia Generale
Piccin Ed.

Robbins Kumar Cotran
The pathologic basis of disease
Elsevier

Educational objectives

Knowledge of molecular and cellular mechanisms of cellular regressive processes and adaptation mechanisms of cells and tissues. Aging and aging mechanisms. Tissue repair mode. Types of functions and usefulness of stem cells

Prerequisites

Physics, chemistry and cell biology. Basic genetics. Biochemistry of nucleic acids, proteins and lipids.
Histology. Human anatomy. Elements of Immunology

Teaching methods

Lectures, class discussions, visualization and commentary of images and laboratory procedures. Viewing movies. Work in a group. Inverted classes. Peer to peer teaching

Learning verification modality

Itinere verification in the classroom

Extended program

REGRESSIVE CELLULAR PROCESSES. Intracellular degenerations. Fatty. Vacuolar and hydropic degeneration. Turbid swelling. Hyaline and mucous degeneration.

EXTRACELLULAR REGRESSIVE PROCESSES. Amyloidosis, hyaline, fibrinoid and mucous degeneration. Pathology of the extracellular matrix components: fibrosis, sclerosis. Cirrhosis.

PATHOLOGY AND PATHOPHYSIOLOGY OF THE EXTRACELLULAR MATRIX. Structure, biosynthesis and degradation of the components of the matrix and its alterations. Cell-matrix interactions and their alterations.

CELLULAR AND TISSUE ADAPTIVE PHENOMENA

HYPOTHROPHY AND ATROPHY
PROGRESSIVE PROCESSES: HYPERTROPHY AND HYPERPLASIA

SENESCENCE AND AGING. Senescence theories. Cell senescence in intermitotic and post-mitotic cells. Molecular level senescence analysis. Re plicative and stress senescence. Aging of the organism. Aging pathology.

III - REPAIR AND REGENERATION

Outcomes of cell damage and inflammatory processes.
The reparative processes and the granulation tissue.
Wound repair
Tissue regeneration.
Stem cells: definition, types, potential and regenerative medicine