Flashcards in Cell Injury and Necrosis Deck (32):
What is the final common pathway of cellular injury (Regardless of cause)
1. Interruption of ATP synth.
2. Damage to cell membranes
3. Free radical damage to membrane lipids, molecules
4. Influx of Na and Ca
5. Activation of Damaging Enzymes
6. Loss of organelle integrity (cytoskeleton)
7. Nuclear Disassembly
ATP depletion leads to --->
Less maintained ion gradients
Cell Swelling + Dilation of Endoplasmic Reticulum
Switch to anaerobic glycolysis (intracellular acidosis)
Detachment of ribosomes
High intracellular Ca
Marks of irreversible mitochondrial damage
Formation of a high-conductance mitochondrial channel, can't maintain membrane potential. Leaks cytochrome C into the cytosol, triggering apoptosis.
Common types of free radical damage
Lipid peroxidation of membranes
Oxidative modification of proteins
Formation of thymidine dimers + ss breaks
How do cells prevent free radical damage
Catalase, Superoxide dismutase, antioxidants, and scavengers, glutathione peroxidase
Who injures you faster -- hypoxia or ischemia?
First system affected by hypoxia?
How long can brain be hypoxic before necrosis? Liver?
Brain -- 3-5 minutes
Liver -- 1-2 hours
Common mechanisms of injury by free radicals
1. Peroxidation of Membrane Lipids. Can lead to H2O2, which propagates the rxn, leading to severe membrane damage.
2. Oxidative modification of proteins, promoting sulfhydryl linking of S containing AAs
3. Single Strand DNA breaks, thymidine dimers
Describe the mechanism of reperfusion injury?
Reestablishment of metabolic pathways with free radical byproducts, influx of cells that produce free radicals (inflam.)
Describe Carbon tetrachloride injury
Formation of highly reactive free radical CCl3.
Auto-oxidation of fatty acids with organic peroxides.
Damage to lipid export --> Fatty Liver
Describe acetaminophen chemical injury
Electrophillic, highly toxic metabolite
normally detoxified by GSH
Covalent binding of toxic metabolites with lipid peroxidation
Describe Fenton Reaction/Hemochromatosis
Iron not metabolized, deposited in tissues.
Chronic damage --> Cirrhosis, diabetes, heart failure
Also tied to liver cancer
Subcellular/Ultrastructural Signs of Reversible Cell Injury
Dilation, Loss of polysomes in the ER
Mitochondrial Swelling, Densities
Clumping, Lysis of Chromatin
Microscopic signs of reversible cell injury
CELL SWELLING AND FATTY CHANGE, Vacuolization, Nuclear Changes
Gross changes in reversible injury
Changes in coloration or tissue consistency
_____ is typically indicative of necrosis
Pyknosis (Loss of nuclear integrity)
Two key features of necrosis
1. Inability to reverse mitochondrial dysfunction
2. Disruption of membranes leading to dissolution of cell
Three main causes of morphological changes --> irreversible injury
Enzymatic Digestion (release of enzymes, infil of leuko.)
Denaturation of protein, lipids, and nucleic acids
Disruption of membranes
Cytoplasmic changes associated with necrosis?
Eosinophilia (Loss of RNA/Ribosomes)
Hyalinization (Loss of glycogen/organelles)
Vacuolation (oh crap - this one is both)
Three main types of nuclear changes associated with necrosis
Pyknosis, Keryorrhexis, Karyolysis
Solid, shrunken basophilic mass
Increased basophilia of chromatin
Pyknotic nucleus undergoes fragmentation
Dissolving of nucleus into amorphic mass
Describe coagulative necrosis
Absent or karyorrhectic nucleus
Cell outlines preserved
Tissue organization remains intact for days
Describe liquefactive necrosis
Large neutrophil infiltration, architecture destroyed
Soft/Liquid Mass, Capsule
How does liquefactive necrosis happen?
Pyogenic bacterial infection usually. Can be fungal of G- bacteria. They stimulate neutrophil migration. PMNs will release proteolytic enzymes that will liquefy the tissue.
Exception to the rule on liquefactive?
Happens in brain necrosis, may have no PMN infiltrate
What is gangrenous necrosis?
Coagulative necrosis associated with loss of blood supply (dry gangrene)
Associated with limbs
Secondary liquefactive necrosis --> Wet gangrene
What is caseous necrosis? Tissue features?
Type of coagulative associated with myco. infection.
Central areas of amorphous, eosinophlic granular material,
Indistinct cell boundaries, surrounded by mps and giant cells. Granulomatous.
General features of fat necrosis?
Destruction of adipose tissue associated with abnormal release of activated pancreatic lipases into the pancreas/peritoneum. Associated with TRAUMA.
The combination of calcium and degrading lipids/proteins results in calcium soaps