1. General Pathology – Seminar 2 Necrosis Atrophy - causes Jaroslava Dušková Inst. Pathol.,1st Med. Faculty, Charles Univ. Prague http://www1.lf1.cuni.cz/~jdusk/

2. Death irreversible damage of the morphological & functional integrity of organism cells

3. Cell Death v apoptosis v necrosis

4. Apoptosis  induced (from outside) or  genetically programmed cell death (cell execution / suicide) v logical and functional contrary to mitosis v a system for the removal of unnecessary, aged, or damaged cells

5. Triggered by a wide range of stimuli. Cell surface receptors like Fas or tumor necrosis factor receptor 1 (TNFR1). Interplay of proapoptotic ( Bax, Bad, Bid, Bik, and Bim) and antiapoptotic (Bcl-2 and Bcl-XL) proteins Apoptosis -1

6. Apoptosis Morphology – chromatin condensation – cell shrinkage – budding and forming of apoptotic bodies (emission of pseudopodia) –karyorrhexis (not pathognomonic for apoptosis)

7. Apoptosis Meaning v physiological process necessary for right organ formatting and life course v pathological process leading to organism damage - e.g. atrophy

8. Apoptosis Ontogenesis intestinal mucose, genit. tract, immune system - T lymphocytes Regeneration of tissues and organs intestinal mucose, blood Physiological involution neonatal adrenal cortex, thymus, breast after lactation period Atrophy preassure, hyperplasia regression, slight ischemia

9. Necrosis cell death caused from external insult

10. Necrosis Biochemistry –no expression of genes de novo –energy dependent membrane systems damaged hypoxia, toxins – changes in concentrations of ions – increased water volume (oncosis) – autolysis

11. Necrosis Morphology – pyknosis, karyorhexis, karyolysis – denaturation of proteins - eosinophilia – cell swelling – cell budding (cytoplasmic protrusions)

12. Necrosis Meaning pathological process leading to a temporary organism damage or death

13. Necrosis Classification according to the tissue macroscopy: – simple – liquefaction – coagulation + special types: caseation, Zenker´s of waxy appearance

14. Necrosis - further development: – no death of organism – gangrene sicca (dry g.) humida (wet g.) emphysematosa (gas g.) – demarcation, sequestration regeneration repair

15. Necrosis - Causes: u chemical –chlorinated hydrocarbons, heavy metal compounds, ethyl- alcohol, aphlatoxins,... u physical –mechanical trauma, UV light, ionizing radiation, heat, cold, …. u biologic –bacteria, viruses, fungi...

16. Atrophy diminution of organ or tissue after full development has been attained ( versus hypoplasia, aplasia) v simple (x hypertrophy) v numerical (x hyperplasia)

17. Atrophy - causes: v vascular v pressure v inactivity v inanition v neurogenic v ionizing radiation v involution v senile v postinflammatory v endocrine v unknown cause

18. Atrophy - meaning: v may be reversible v loss of specialised structures & hypofunction v clinically silent or unimportant (involution) v clinically apparent v metaplasia, increase of the supportive tissues - pseudohypertrophy