Cell Injury and Necrosis

Question 1

What is the final common pathway of cellular injury (Regardless of cause)

Answer 1

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

Question 2

ATP depletion leads to —>

Answer 2

Less maintained ion gradients
Cell Swelling + Dilation of Endoplasmic Reticulum
Switch to anaerobic glycolysis (intracellular acidosis)
Detachment of ribosomes
High intracellular Ca

Question 3

Marks of irreversible mitochondrial damage

Answer 3

Formation of a high-conductance mitochondrial channel, can’t maintain membrane potential. Leaks cytochrome C into the cytosol, triggering apoptosis.

Question 4

Common types of free radical damage

Answer 4

Lipid peroxidation of membranes
Oxidative modification of proteins
Formation of thymidine dimers + ss breaks

Question 5

How do cells prevent free radical damage

Answer 5

Catalase, Superoxide dismutase, antioxidants, and scavengers, glutathione peroxidase

Question 6

Who injures you faster – hypoxia or ischemia?

Answer 6

Ischemia

Question 7

First system affected by hypoxia?

Answer 7

Oxidative Phos

Question 8

How long can brain be hypoxic before necrosis? Liver?

Answer 8

Brain – 3-5 minutes

Liver – 1-2 hours

Question 9

Common mechanisms of injury by free radicals

Answer 9

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

Question 10

Describe the mechanism of reperfusion injury?

Answer 10

Reestablishment of metabolic pathways with free radical byproducts, influx of cells that produce free radicals (inflam.)

Question 11

Describe Carbon tetrachloride injury

Answer 11

Formation of highly reactive free radical CCl3.
Auto-oxidation of fatty acids with organic peroxides.
Damage to lipid export –> Fatty Liver

Question 12

Describe acetaminophen chemical injury

Answer 12

Electrophillic, highly toxic metabolite
normally detoxified by GSH
Covalent binding of toxic metabolites with lipid peroxidation

Question 13

Describe Fenton Reaction/Hemochromatosis

Answer 13

Iron not metabolized, deposited in tissues.
Chronic damage –> Cirrhosis, diabetes, heart failure
Also tied to liver cancer

Question 14

Subcellular/Ultrastructural Signs of Reversible Cell Injury

Answer 14

Membrane Blebbing
Dilation, Loss of polysomes in the ER
Myelin Figures
Mitochondrial Swelling, Densities
Clumping, Lysis of Chromatin

Question 15

Microscopic signs of reversible cell injury

Answer 15

CELL SWELLING AND FATTY CHANGE, Vacuolization, Nuclear Changes

Question 16

Gross changes in reversible injury

Answer 16

Changes in coloration or tissue consistency

Question 17

_____ is typically indicative of necrosis

Answer 17

Pyknosis (Loss of nuclear integrity)

Question 18

Two key features of necrosis

Answer 18

1. Inability to reverse mitochondrial dysfunction

2. Disruption of membranes leading to dissolution of cell

Question 19

Three main causes of morphological changes –> irreversible injury

Answer 19

Enzymatic Digestion (release of enzymes, infil of leuko.)
Denaturation of protein, lipids, and nucleic acids
Disruption of membranes

Question 20

Cytoplasmic changes associated with necrosis?

Answer 20

Eosinophilia (Loss of RNA/Ribosomes)
Hyalinization (Loss of glycogen/organelles)
Vacuolation (oh crap - this one is both)

Question 21

Three main types of nuclear changes associated with necrosis

Answer 21

Pyknosis, Keryorrhexis, Karyolysis

Question 22

Describes pyknosis

Answer 22

Solid, shrunken basophilic mass

Increased basophilia of chromatin

Question 23

Describe karyorrhexis

Answer 23

Pyknotic nucleus undergoes fragmentation

Question 24

Describe karyolysis

Answer 24

Dissolving of nucleus into amorphic mass

Question 25

Describe coagulative necrosis

Answer 25

Absent or karyorrhectic nucleus
Cell outlines preserved
Eosinophillic cytoplasm
Tissue organization remains intact for days

Question 26

Describe liquefactive necrosis

Answer 26

Large neutrophil infiltration, architecture destroyed

Soft/Liquid Mass, Capsule

Question 27

How does liquefactive necrosis happen?

Answer 27

Pyogenic bacterial infection usually. Can be fungal of G- bacteria. They stimulate neutrophil migration. PMNs will release proteolytic enzymes that will liquefy the tissue.

Question 28

Exception to the rule on liquefactive?

Answer 28

Happens in brain necrosis, may have no PMN infiltrate

Question 29

What is gangrenous necrosis?

Answer 29

Coagulative necrosis associated with loss of blood supply (dry gangrene)
Associated with limbs
Secondary liquefactive necrosis –> Wet gangrene

Question 30

What is caseous necrosis? Tissue features?

Answer 30

Type of coagulative associated with myco. infection.
Central areas of amorphous, eosinophlic granular material,
Indistinct cell boundaries, surrounded by mps and giant cells. Granulomatous.

Question 31

General features of fat necrosis?

Answer 31

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

Question 32

What do you see when you look microscopically at fat necrosis?

Answer 32

Eosinophilic ghost outlines of necrotic adipocytes
Basophilic Ca deposits
Inflammation