1 Growth Adaptions, Cell Injury & Death Flashcards
Hypertrophy
Increase in size of cells via gene activation & protein synthesis to increase amount of cystoskeleton + increased production of organelles
NOTE: Cardiomyocytes, skeletal muscle, nerve tissue use hypertrophy ONLY, no stem cells
Hyperplasia
Increase in number of cells from stem cells
Pathologic hyperplasia to dysplasia to cancer
(Physiologic hyperplasia is okay)
Atrophy
Decrease in size via ubiquitin-proteosome degradation of cytoskeleton + autophagy (vacuole with lysosome) of cell components
Decrease in number of cells via apoptosis
Metaplasia
Squamous epithelium (Keratinizing, Non-keratinizing)
Columnar epithelium
Transitional epithelium/ Urothelium
Mesenchymal tissues
Metaplasia
-Via “reprogramming stem cells”
-Reversible! Remove the stressor
-Vitamin A deficiency (needed for specialized epithelium)
Metaplasia to dysplasia to cancer
(Except: Apocrine metaplasia of breast)
Dysplasia
Disordered cell growth
Proliferation of precancerous cells
Longstanding pathologic hyperplasia or metaplasia
Reversible! Remove the stressor
Progress to carcinoma, which is irreversible
Cell Injury
When cells cannot overcome the stress
-Inflammation
-Hypoxia
-Trauma
-Genetic mutations
-Nutritional deficiency/ excess
Hypoxia
Ischemia
Hypoxemia
Reduced carrying capacity of o2 by Hb
- CO poisoning
- Methemoglobinemia
Hypoxia impairs oxidative phosphorylation, ATP production
ATP needed for Na+/K+ pump which maintains fluid balance & Ca++ pump which keeps Ca++ out of cell/ from activating enzymes
Phases of Cell Injury
Reversible Injury Phase
=Cellular swelling (as Na+ builds up in cell)
-Loss of microvilli
-Membrane blebbing
-Swelling of RER, decreased protein synthesis
Irreversible Injury Phase
=Membrane damage (of three membranes)
-Cell contents spill out (Ex. Cardiac troponin)
-Increase intra-cellular Ca++
-Loss of electron transport chain
-Cytochrome C leaks out, +Apoptosis
-Lytic enzymes escape lysosome
Cell Death
Loss of nucleus via
1. Pyknosis (nucleus shrinks)
2. Karyorrhexis (nucleus breaks up)
3. Karyolysis (pieces breaks up into building blocks)
Necrosis
Death of large group of cells
Followed by acute inflammation
Pathologic process
Coagulative Necrosis
Tissue remains firm
Coagulation of cell proteins
No nuclei
Seen in ischemic infarction (Except: Brain)
-Infarct is wedge-shaped & pale
-Red infarct if blood re-enters, if tissue loosely organized
Liquefactive Necrosis
Dead tissue becomes liquefied
Enzymatic lysis of cells & proteins
Brain infarct - Microglial cells, hydrolytic enzymes
Abscess - Neutrophils, hydrolytic enzymes
Pancreatitis - Pancreatic enzymes
Gangrenous Necrosis
Coagulative necrosis that resembles mummified tissue, dry gangrene
Seen in ischemia of lower limb in diabetic patients
Superimposed infection of dead tissue causes liquefactive necrosis, wet gangrene
Caseous Necrosis
Liquefactive + coagulative
Soft, friable dead tissue with “cottage cheese” appearance
Seen in granulomatous inflammation in TB or fungal infection
Fat Necrosis
Dead fatty tissue
1. Free fatty acids bind with Ca++
2. Saponification
3. Chalky-white appearance because Ca++ deposition
Due to trauma to fat, pancreatitis-related damage of peri-pancreatic fat
Calcification
Dystrophic Calcification
-Saponification (fat necrosis)
-Psammoma bodies (tumor outgrow blood supply)
Metastatic Calcification
-Serum Ca++ or Phos is elevated, forces Ca++ into tissues, & Ca++ precipitates
-Does not mean CA!
Fibrinoid Necrosis
Dead blood vessel wall
Proteins leak from vessel into wall, see bright pink staining (hyaline)
Seen in malignant HTN or vasculitis or pre-eclampsia (fibrinoid necrosis of placental blood vessels)
Apoptosis
Energy-dependent
Genetically programmed
Single cells or small groups of cells
Ex. Endometrial shedding during menstrual cycle
Ex. Embryogenesis
Ex. CD8+ killing of virally infected cells (via MHC-1)
Cell shrinks, turns pink because cytoplasm concentrates
Nucleus condenses, shrinks, fragments
Apoptotic bodies cleared by macrophages
No inflammation!
Apoptosis Mediated by Caspases
-Activate proteases for cytoskeleton
-Activate endonucleases for DNA
Intrinsic Mitochondrial Pathway (of Apoptosis)
Activated by cell injury, DNA damage, decreased hormone stimulation that inactivates BCL2
Without BCL2, cytochrome C leaks out into cytoplasm & activates caspases
Extrinsic Receptor-Ligand Pathway (of Apoptosis)
Something from outside world binds to cell receptor, initiating apoptosis
Ex. FAS ligand binds FAS death receptor (CD95) on T cell in negative selection (when T cell binds too strongly to self-Ag)
Ex. TNF binds TNF receptor
Cytotoxic CD8+ T Cell Pathway (of Apoptosis)
CD8+ recognizes its Ag on MHC-1
-Releases perforins to create holes in target cells
-Releases granzyme to enter pores & activate caspases
Free Radicals
Chemical species with unpaired electron
-Normally generated in electron transport chain
-Pathologically generated by ionizing radiation, inflammation, Cu & Fe, drugs
***Hydroxyl free radical is most damaging
Free radical damage via…
-Peroxidation of lipids, in membranes
-Oxidation of DNA & proteins
Elimination of Free Radicals
Antioxidants, vit A/C/E
Metal carrier proteins for Cu & Fe
Enzymes
-Superoxide dismutase for o2-
-Catalase for h2o2
-Glutathione peroxidase for OH-
Free Radical Injury
Carbon Tetrachloride (CCl4)
-Classically seen in dry-cleaning industry
-Gets into blood, converted to CCl3 by P450 system
-CCl3 free radical damages hepatocytes
-Reversible damage with cell swelling & loss of RER
-Decreased protein synthesis & apolipoproteins
-Fatty accumulation/ change in liver
Reperfusion Injury
-Reduced ability of dead tissue to deal with free radicals, causing even more injury in that area
