Inflammation Flashcards
Early morphological changes in cell injury (reversible)
swelling (membrane damage) Mitochondrial swelling (Hypoxia) Endoplasmic Reticulum swelling - polyribosomes detach Nucleolus changes
Two examples of metaplasia
Columnar epithelium in bronchus –> squamous epithelium in response to smoking
Squamous epithelium –> columnar epithelium in esophagus from GERD (Barrett’s esophagus)
Classic Necrosis
- Ca leaks into the cell and is released from organelles, activating enzymes and proteases and opening the mitochondrial membrane permeability transition pore (MTP)
- Cell loses ability to make ATP, and everything swells and the membrane blebs, loss of membrane integrity
- Nonspecific degradative smear of DNA fragments
Classic Apoptosis
Programmed cell death, activated by extracellular ligand binding (Fas/FasR) and cytochrome c release from mitochondria activates caspases
Cytoplasm shrinks, cytoplasm buds and forms apoptotic bodies that are taken up by macrophages.
-Internucleosomal DNA breakage
Coagulative necrosis
Characteristics of infarcts
Architecture preserved for several days (proteins AND enzymes damaged)
Dead cells remain pale and white
Leukocytes digest dead cells
Liquefactive necrosis
- Focal bacterial or fungal infections because microbes stimulate inflammatory cells
- Leukocyte enzymes “liquefy” (digest) tissue
- Hypoxic cell death in CNS –> liquefactive necrosis
- Dead cells are completely digested and removed by phagocytes
Caseous necrosis
- TB infection
- Central portion of infected tissue is necrotic (toxic mycobacteria effects)
- Fragmented cells and amorphous debris are surrounded by granulomatous inflammation
Fat necrosis
- Areas of fat destruction, resulting from release of activated pancreatic lipases following acute pancreatitis or trauma
- Fats are hydrolyzed into free fatty acids and precipitate with Ca++ to make a chalky grey material
7 causes of cell/tissue injury
1) physical agents (heat, trauma)
2) Chemical and drugs (toxicity, poisoning)
3) Infection
4) Immunologic insults (anaphylaxis, autoimmunity)
5) Genetic derangement (CF, PKU)
6) nutritional imbalance (atherosclerosis, vitamin deficiency)
7) Hypoxia
Reversible changes due to hypoxia (Cell swelling)
1) ↓ ATP
2) ↓ Na pump (cell swelling)
3) ↑ glycolysis, ↓ pH
4) ↓ protein synthesis
Irreversible changes (Membrane damage)
1) Activation of lysosomal enzymes
2) DNA, protein degradation
3) ↑ Ca 2+ influx
Secondary injury from oxygen radicals
1) O2 therapy produces high levels of O2 radicals, esp. in lung
2) Inflammation - PMN’s have enzymes like myeloperoxidase which make O2 radicals
3) Reperfusion - in hypoxia, xanthine dehydrogenase is proteolytically converted to xanthine oxidase, and this will create o2 radicals once hypoxia is fixed
Oxygen free radicals
O2- (superoxide) and •OH
-Generated by intrinsic oxidases and radiation
Free Radical removal
Superoxide removed by SOD making H202
-If H202 isn’t sufficiently removed by catalase, hydroxyl radical forms
Antioxidants, catalase, and glutathione peroxidase remove these radicals
4 key features of acute inflammation
fast; neutrophils, mild/self limited tissue injury/fibrosis, prominent local and systemic signs
4 key features of chronic inflammation
Slow (days)
Monocytes/macrophages and lymphocytes
severe/progressive tissue injury/fibrosis
Less local/systemic signs
Major causes of acute inflammation
trauma infection any cause of necrosis foreign material (splinter, suture) immune reactions (allergies)
Toll-like receptors
10 forms in humans
Recognize microbial materials
Activate transcription factors that upregulate inflammatory mediators, interferons (interfere with infectious agents), and promote lymphocyte activation
Inflammasome
Complex of many receptors that stimulate inflammation by activating caspase 1
Receptors recognize microbial components and pieces of dead cells (ATP just floatin)
Caspase 1 action
-Forms active Interleukin 1 beta
-IL-1ß recruits leukocytes to clean up dead cells
(activated by inflammasome)
Exudate
High protein content and may contain some white and red cells
Allowed by increased vasodilation and permeability during inflammation
Transudate
low protein content, few cells
Vasodilation in acute inflammation
Arterioles swell flooding effected capillary beds (rubor and calor)
As fluid leaves vessels, cells are left behind (slow blood flow and stasis)
Increased permeability in acute inflammation (3 mxns)
(1) endothelial cell contraction
(2) Injury of endothelial cells (activated leukocytes may release toxic compounds to injure endothelial cells)
(3) Transcytosis - vesicular transport accross membrane