CELL INJURY and CELL DEATH

Reversible Injuries: (Two types of changes can be gleaned using the light microscope)  Cellular swelling (hydropic change/degeneration) o e.g. Hydatidiform mole characterized by vesicle formation  Fatty change (steatosis) o e.g. fatty liver characterized grossly by an increase in weight from normally 1.1-1.3kg to 4-6kg and will appear yellowish and greasy o histologically, accumulation of lipid vacuoles pushing the nuclei to the periphery signet ring sign; also has a sieve-like appearance

y y

y y

Local deficiency in the blood supply (ischemia) limited oxygen and glucose supply In the hypoxic state, the most commonly affected organelle is the mitochondrion (site of oxidative phosphorylation) mitochondrial activity will lead to ATP production ATP will lead to a decreased level of activity of the ATP dependent Na-K pumps located at the cell membrane Na remains in the cell and attracts water which leads to cellular swelling In the hypoxic state, the cell shifts to anaerobic glycolysis whose end product is pyruvate which will be reduced to lactic acid thus resulting in a decrease in pH clumping of chromatin(ECF: 7.4; ICF:7-7.3)

* Cell death can either be necrosis or apoptosis which are distinct from one another Features Cell size Necrosis Enlarged (swelling) Apoptosis Reduced (shrinkage)

SY 2011-2012

Subject: Pathology Pre-lab discussion Topic: Cell Injury and Death Lecturer: Dr. Kent Ermita Date of Lecture: 06/16/2011 Transcriptionist: porkanor Pages: 2

Nucleus

Pyknosis karyorrhexis karyolysis

Fragmentation into nucleosomesize fragments Intact; altered structure, especially orientation of lipids Intact; may be released in apoptotic bodies No

Plasma membrane

Disrupted

Cellular contents

Enzymatic digestion; may leak out of cell

Adjacent Frequent inflammation Physiologic or Pathologic role Invariably pathologic (culmination of irreversible cell injury)

Often physiologic, means of eliminating unwanted cells; may be pathologic after some forms of cell injury, especially DNA damage

Enzymatic fat necrosis - Release of activated pancreatic lipase liquefies membranes of fat cells in the peritoneum. - Fatty acid when combined with calcium form chalky white areas Caseous/ Caseation necrosis - Tuberculous infection - Complete obliteration of tissue architecture - Friable(crumbly) yellow-white areas of necrosis - Characteristic focus of inflammation: GRANULOMA  collection of transformed macrophages called epitheloid cells (hallmark of granuloma formation) rimmed by lymphocytes  may have Langhan s type giant cells Gangrenous necrosis - e.g. Lower limb that has lost its blood supply. - e.g. appendicitis  there is obliteration of the layers of the appendiceal wall - Coagulative necrosis is transformed by liquefaction action of enzymes released by leukocytes when there is superimposed bacterial infection

*table taken from Robbins Basic Pathology 8th ed. p.6

Irreversible Injuries: NECROSIS  Increased eosinophilia  Nuclear changes o PYKNOSIS- shrinkage and increased basophilia o KARYOLYIS- dissolution and fading of chromatin o KARYORRHEXIS- fragmentation  PATTERNS OF NECROSIS o Coagulation necrosis/ COAGULATIVE necrosis  Infarction of solid organs except brain  Denaturation of proteins as well as enzymes blocking proteolysis of necrotic cells  Basic tissue architecture is preserved (tombstone) o Liquefaction necrosis/ LIQUEFACTIVE necrosis - CNS, focal bacterial infections with accumulation of inflammatory cells - Enzymatic digestion of dead cells transforming tissues into liquid viscous mass - Obliteration of tissue architecture

Intracellular Accumulations: 1. Lipids A. Fatty change, Liver B. Atherosclerosis (Coronary Artery) 2. Pigments A. Exogenous  carbon (most common exogenous pigment; anthracotic pigment) B. Endogenous  lipofuscin (insoluble yellowish brown granular material)  hemosiderin (golden yellowbrown granular pigments derived from hgb)  melanin (black-brown pigment produced by melanocytes) 3. Other cellular accumulations A. Dystrophic calcifications o Affinity of calcium to necrotic tissue o No disturbance in calcium balance as opposed to metastatic calcification B. Hyaline change ____________END OF TRANSCRIPTION_________
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