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Etiology and Pathogenesis הרצאה 3. Disease - Definition.
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Disease - Definition • A disease is any abnormal condition of the body or mind that causes discomfort, dysfunction, or distress to the person affected or those in contact with the person. Sometimes the term is used broadly to include injuries, disabilities, syndromes, symptoms, deviant behaviors, and atypical variations of structure and function, while in other contexts these may be considered distinguishable categories. • Pathology is the study of diseases. The subject of systematic classification of diseases is referred to as • nosology. The broader body of knowledge about diseases and their treatments is medicine.
Classification of Diseases: • Developmental – genetic, congenital. • Inflammatory – Trauma, infections, immune, etc. • Neoplastic – tumors, cancers • Degenerative – aging.
Pathology Study of Disease: • Epidemiology • Etiology - Causes • Pathogenesis - Evolution • Morphology - Structural Changes • ClinicalSignificance –Functional Changes Clinical manifestation • Complications • Prevention
אטיולוגיה: מהו הגורם הראשוני פתוגנזה: מהו מנגנון ההתפתחות מורפולוגיה: השנויים המבניים משמעות קלינית: השנויים התפקודיים ETIOLOGY: Cause of disease. PATHOGENESIS: Mechanisms of development of disease. MORPHOLOGY: The structural alterations induced in cell and tissues. FUNCTIONAL CONSEQUENCES: Functional consequences of the morphologic changes, as observed clinically. Knowledge of etiology remains the backbone: Disease diagnoses Understanding the nature of diseases Treatment of diseases. Pathology focuses on 4 aspects of diseaseהמרכיבים העיקריים בחקר המחלה
(etios+logos)ETIOLOGYאטיולוגיה: - גורמים etiology גנטיים (endogenous causes)סיבות פנימיות נרכשים (exogenous causes)סיבות חיצוניות המושג: "גורם אחד = מחלה אחת", היה מקובל בעבר. התברר, שלרוב, אינו נכון.
Etiology: • Environmental agents: • Physical • Chemical • Nutritional • Infections • Immunological • Psychological • Genetic Factors: • Age • Genes Multifactorial:
Exogenic causes ( סיבות חיצוניות): 1. physical factors (גורמים פיזיקליים). 2. chemical factors (גורמים כימיים). 3. infections (זיהומים ). 4. environmental factors (גורמי סביבה). 5. Psychogenic factors (פסיכוגניים ). 6. Iatrogenic factors (יאטרוגניים).
physical factors (גורמים פיזיקליים): mechanical trauma pressure temperature ( cold, hot, fire) radiation: ultraviolet x-rays radioactive laser electromagnetic waves
chemical factors (גורמים כימיים): irritative substance poisons drugs infections (זיהומים ): bacterial fungal parasitic viral prions (Kreutzfeldt-Jakob, kuru)
Environmental factors (גורמי סביבה): contact with some materials: carbon silica asbest industrial pollutions deficiency of vitamins or minerals deficiency of food Psychosocial factors ((גורמים פסיכוסוציאלים: emotional stress
Iatrogenic factors (גורמים יאטרוגניים): chemotherapy: immunodeficiency dialysis: bone abnormalities immunodeficiency amyloidosis transplantation: rejection GVHD immunodeficiency drug complications: pseudomembranous colitis hypersensitivity reactions
Endogenic causes (סיבות פנימיות ): ( mostly - genetic disease ) 1. a-dominant diseases: Morfan syndrome neurofibromatosis achondroplasia von Hipple-Lindau 2. a-recessive diseases: cystic fibrosis phenylketonuria Tay-Sachs disease 3. x-linked diseases: hemophilia G6PD deficiency 4. Multifactorial genetic diseases: congenital malformations diabetes
Diseases of unknown origin: Lupus erythematosus (LE) Rheumatoid arthritis (RA) Polyarteriitis nodosa (PAN) Sjogren's syndrome Sarcoidosis
Role of conditions ( תנאים )in development of disease: Many diseases is not always expressed even in presence of causal factors. For example: Meningococcal infection: no disease nasopharyngitis meningitis meningococcemia Expression of disease depends on status of host(immune system, nutrition, presence of other diseases.)
Risk factors (גורמי סיכון) It may be very difficult or even impossible to distinguish between causal factors and conditions in some diseases.
Risk factors influencing for development of ischemic heart disease (IHD): Heredity Age Smoking Hypercholesterolemia Oral contraceptives Hypodynamia Hypertension Diabetes High stress life style
One etiologic agent—one disease. Several etiologic agents—one disease. One etiologic agent—several diseases.
Diseases are “caused” due to internal or external factors. • Multifactorial: No more “one cause to one disease” • Genetic factors affect acquired diseases and environment has profound effect on genetic diseases.
(pathos+genesis)PATHOGENESIS Pathogenesis is chain of biological reactions triggered by causal factor and leading to expression of disease. רצף של תגובות ביולוגיות המתפתחות בגוף כתוצאה ראשוני (סיבהמהשפעת גורם ראשוני (סיבה אטיולוגית) ומביאות לביטוים קליניים ומורפולוגיים של מחלה.
For example - Pathogenesis of burn (כויה): Fire 6 Termal injury of skin 6 Release of arachidonic acid 6 Synthesis of leukotriens and prostoglandins 6 Vascular permiability, vasodilatation, chemotaxis, pain, edema. Clinical expression (ביטוים כליניים): rubor, dolor, tumor, calor, loss of plasma.
Complications: 1. pain + loss of plasma 6 shock 2. absence of skin barier 6 infection 6 sepsis 6 shock
Etiology and pathogenesis in context of prevention and treatment of disease. 3 types of treatment: etiologic pathogenetic symptomatic
Etiologic treatment - against cause of disease. Examples: Infections - antibacterial, antifungal, antiviral therapy. Vitamin deficiency - vitaminotherapy. Iron deficiency anemia - Fe therapy.
Pathogenetic treatment: cause is unknown or causal factor is no longer active. Examples: - mechanical trauma - burn (כויה) - postinfective autoimmune deseases (rheumatic fiver, PIGN ).
Prevention of diseases: vaccinations (חיסונים) genetic consultations (יעוץ גנטי) prohibition of some materials decrease of risk factors.
Pathology Summary: • Etiology: • Carcinogenesis. DNA Damage, Mutation. • Pathogenesis: • Uncontrolled cell division, tumor. • Morphology: • Enlarged lymphnodes, liver, spleen, microscopically – lymphoma cells. • ClinicalFeatures: • Fever, Wt loss, tumor-Ln, Liver, Spleen.