Aetiology, pathogenesis, course of diseases. Aetiology. course of diseases. diseases. General pathophysiology Terminology Clinical examples

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1 Aetiology, pathogenesis, course of diseases Attila Tóth UDMHSC Institute of Cardiology Division of Clinical Physiology Aetiology, pathogenesis, course of diseases General pathophysiology Terminology Clinical examples Aetiology causes of diseases and the conditions that influence the development of diseases "aitia" = cause; "logos" = discourse (Greek) 1

2 Primary causes of diseases Exogenous: living organisms (bacteria, viruses, helminthes, protozoons, arthropods, mycetes), physical factors (heat, radioactivity, vibration and other mechanical effects, electricity), chemical factors (poisons, heavy metals), Endogenous: genetic disorders (e.g. familial hypercholesterolaemia) missing or altered LDL receptors Familial hypercholesterolaemia D: missing or altered LDL receptor d: normal LDL receptor Inheritance: autosomal dominant genetic susceptibility + environmental factors: multifactorial disease Conditions (part I) (secondary causes of diseases) Strength and quality of the pathogenic factor Examples: - bacterial infections virulence and number of bacteria - electricity - voltage - direct current (D.C.) / alternating current (A.C.) A.C.: 30 Hz Hz - most dangerous > 2000 Hz thermal effect - electrical resistance - duration of exposition - radioactive exposition dose > 50 Gy death within hours/days (CNS) Gy death within 2 weeks (GI tract) 2-10 Gy may cause death (bone marrow failure) 2

3 Haematological responses on radiation Platelets Lymphocytes 1 Gray (Gy) = 1J absorbed energy / 1 kg Neutrophil granulocytes Days after irradiation Biological effect is reflected by the lymphocyte count following radioactive exposition Absolute lymphocyte count/µl days normal range mild severe very severe deadly severity of injury Resistance of the host Conditions (part II) (secondary causes of diseases) Facilitate: (e.g. malnutrition facilitates the development of tuberculosis) Inhibit: (e.g. dry skin decreases the risk of electrical shock) 3

4 Pathogenesis - the origination and development of diseases - dynamic mechanisms of disturbed function during various diseases - all those processes that develop during the course of diseases - the cellular events and reactions that occur in the development of diseases - "pathos" = suffering or disease; "genesis" = birth, giving rise to ( Greek) General scheme for the establishment and outcome of infectious diseases 4

5 Exogenous pathogens enter via various portals of entry a./ ingression - the respiratory tract (inhalation) - gastrointestinal tract and upper respiratory tract (ingestion) b./ skin and mucus membrane entry (contact) c./ penetration - insect bites - cuts and wounds - Iatrogenic (e.g. intravenous catheters) lost barrier function (e.g. immunodeficiency, tissue damages) weak resistance: locus minoris resistentiae Primary localization and colonization depend on the: a./ portal of entry b./ tissue affinity (organotropism) of the invading agent (e.g. dermotropic, neurotropic, viscerotopic viruses/bacteria) c./ inoculum size (quantity of infectious organisms) d./ properties of the host Progression of an illness and routes of spread a./ direct spread: - from cell to cell (e.g.: inflammation) - intracanalicular spread (e.g.: inflammation of the bile duct, tuberculosis of bronchi, ascending urogenital infection) b./ spread during transient tissue contacts (e.g.: perigastritis during gallbladder inflammation, urogenital herpes) c./ spread via lymphatics and blood, i.e. metastatic spread (e.g. cancers, syphilis, bacteria during septicaemia, tuberculosis d./ spread via neurons/cerebrospinal fluid (e.g. lyssa (rabies), tetanus) 5

6 The development/course of diseases According to the duration and the severity/intensity of the symptoms: a./ Hyperacute disease: 1-2 days, very severe symptoms (e.g.: large MI, stroke) b./ Acute disease: 1-2 days 2-3 weeks, severe symptoms (e.g.: pneumonia, cholera) c./ Subacute disease: 3 weeks 6 weeks, less severe symptoms (e.g.: subacute infective endocarditis) d./ Chronic disease: longer than 6 weeks, asymptomatic and symptomatic periods (i.e.: paroxysmal exacerbations) complications or consequences of acute diseases (e.g.: chronic glomerulonephritis, chronic hepatitis) - chronic infective illnesses (e.g.: tuberculosis, syphilis) - metabolic illnesses (e.g.: diabetes, gout) Stages of diseases 1. phase: incubation or latent period: no symptoms, no pathologic regulation, (during infective disorders: invasion, spread,) 2. phase: prodrome or introductory phase: uncertain vague symptoms like weakness, headache, slight fever 3. phase: acme i.e. the critical stage or the crisis of a disease. Symptoms are characteristic for the disease (fever, inflammation, intoxication, exanthema, eruptions or rash of the skin). Complications may develop. 4. phase: outcome/progression of a disease. Recovery might be preceded by shorter or longer convalescence. 6

7 Amyotrophic lateral sclerosis (ALS); commonly known in the United States as Lou Gehrig's Disease. Born: January 8, 1942 Stephen William Hawking Possible outcomes of diseases complete recovery ( restitutio ad integrum ): no anatomical or functional alterations remain clinical or functional recovery: regulation returns, some morphologic alterations remain (e.g.: fibrosis in the heart, cirrhosis in liver remaines) development of a chronic disease: (e.g.: endocarditis followed by circulatory disorders) manifestation of a pathologic condition (e.g.: after virus hepatitis cirrhosis, ascites and liver failure ) death 7

8 Stages of death 1./ Clinical death: respiratory and circulatory functions are ceased, preceded by agony (death struggle) 2./ Intermediate life: organ/tissue survival after clinical death: - cerebral cortex and CNS 5-10 minutes - heart minutes - kidney minutes - liver minutes - cornea 24 hours - finger nail, cartilage, hair, bone hours 3./ Biologic death: irreversible alterations, all cells die in the body Aetiology, pathogenesis, course of diseases 8