General Pathology Basic Principles of Cellular and Organ

General Pathology Basic Principles of Cellular and Organ Pathology Infection - I http: //www 1. lf 1. cuni. cz/~jdusk/ Jaroslava Dušková Inst. Pathol. , 1 st Med. Faculty, Charles Univ. Prague

Inflammation - causes v v nonliving physical chemical living prions (? ) viral bacterial mycotic parasitic AUTOIMMUNE

Interaction of Organism and Microorganism – Terms Bacteriemia (transient) v Sepsis/ Septicemia v Pyemia v Toxemia v Viremia v

Bacteriemia v transient presence of microbes in the bloodstream

Sepsis / Septicemia (Severe Bacteremia) u increasing numbers of microbes (& their toxins) in the bloodstream

Sepsis/Septicemia Def. systemic response to infection manifestating as v v tachypnoe tachycardia temperature leucocytosis > 20/min. > 90/min. > 39 st. C. (ev. < 36 st. C) > 15 000/1 l (ev. < 4000/1 l)

Sepsis – Pathogenetic Factors v Endotoxin, toxins G+ TNF, IL– 1 v Macrophages TNF, IL– 1, IL– 6 v Cytokins NO v PAF (Platelets Activating Factor) v NO synthesis vasodilation coagulation

Syndrome of Systemic Inflammatory Response Def. systemic response to an AGENT manifestating as v tachypnoe > 20/min. v tachycardia > 90/min. v temperature > 39 st. C. (ev. < 36 st. C) v leucocytosis > 15 000/1 l (ev. < 4000/1 l) AGENT : pancreatitis, injury, burns…. .

Pyemia u presence of infected thrombemboli bearing virulent microbes in the bloodstream

Toxemia u presence of microbial toxin (s) without the microbes themselves in the bloodstream

Endotoxin u lipopolysaccharide component of G- bacteria outer wall u effects: fever, shock, DIC, RDS u effects mediated by IL-1, TNF

Exotoxins -1 u often enzymes (leukocidins, hemolysins, hyaluronidases, coagulases, fibrinolysins) uothers………….

Exotoxins -2 u diphteria toxin – inhibition of cellular proteosynthesis u botulotoxin – block of the cholinergic transmission u choleratoxin – increase in c. AMP, losses of isoosmotic fluid via enterocytes

Host u. General Microorganism Encounter & u. Successful transmission defenses u. Site of attack u. Inflammation u. Number of microorg. u. Immune status u. Pathogenicity u. Natural

Host u. General – age, race, nutrition, other diseases (diabetes) u. Natural defenses – skin, mucose integrity – mucus, cilliary action, unobstructed flow – protective secretion (lysosym in tears, gastric acid, Ig. A u. Inflammation – leucocytes – macrophages phagocytosis u. Immune status – immunity (or lack of it) active, passive immunisation, contact – lymphocytes – immunoglobulins – complement

Microorganism Successful transmission u Site of attack u Number of microorg. u Pathogenicity invasiveness u toxin production multiplication resistence to host defence mechanisms ability to cause necrosis enzyme release

INFECTION versus DISEASE v Pathogenicity (virulence) v Incubation Period v Carrier State

Agent – Host Interaction cytocidal v stabilised (steady– state) v transformation – ONCOGENS v

Virus – Host Cell Interaction cytocidal v stabilised (steady– state) v transformation – ONCOGENS v

Inflammation - causes v v non infectious physical chemical infectious prions viral bacterial mycotic parasitic AUTOIMMUNE

Infectious Agents of Humans u u prions viruses (DNA, RNA) bacteria (incl. chlamydia, mycoplasma, u rickettsia – obligatory intracellular parasites) u u fungi (yeasts, molds) parasites (protozoa, helmints, ectoparasites- insects: lice, mites, ticks; spiders)

Infectious Agents of Humans Bacteria simple cells – prokaryotes v both DNA and RNA v cocci, bacilli (AFB!), spirochetes…. v Gram positive /negative v extra- and/or intracellular v aerobic/ anaerobic v

Infectious Agents of Humans Fungi complex cells – eukaryotes v both DNA and RNA v yeasts, molds (hyphae, v pseudohyphae…) PAS, impregnation v extra- or intracellular v mostly opportune pathogens v

Infectious Agents of Humans Parasites -1 Protozoa v v v complex cells – eukaryotes both DNA and RNA extra- or intracellular (Amebas, Trichomonas, Trypanosoma, Toxoplasma, Plasmodium, Pneumocystis…)

Infectious Agents of Humans Parasites -2 Metazoa (helmints and flukes) v v multicellular both DNA and RNA flat and round worms extracellular (Taenia, Ascaris, Enterobius, Trichuris Echinococcus, Clonorchis, Schistosoma, Wuchereria…)

Infectious Agents of Humans Parasites -3 Insecta, Arachnida v v v multicellular both DNA and RNA extracellular (Sarcoptes scabiei, fleas, ticks, lice……)