Cell Injury and Necrosis Flashcards Preview

Pathology -- Gen Path > Cell Injury and Necrosis > Flashcards

Flashcards in Cell Injury and Necrosis Deck (32):
1

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

2

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

3

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.

4

Common types of free radical damage

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

5

How do cells prevent free radical damage

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

6

Who injures you faster -- hypoxia or ischemia?

Ischemia

7

First system affected by hypoxia?

Oxidative Phos

8

How long can brain be hypoxic before necrosis? Liver?

Brain -- 3-5 minutes
Liver -- 1-2 hours

9

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

10

Describe the mechanism of reperfusion injury?

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

11

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

12

Describe acetaminophen chemical injury

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

13

Describe Fenton Reaction/Hemochromatosis

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

14

Subcellular/Ultrastructural Signs of Reversible Cell Injury

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

15

Microscopic signs of reversible cell injury

CELL SWELLING AND FATTY CHANGE, Vacuolization, Nuclear Changes

16

Gross changes in reversible injury

Changes in coloration or tissue consistency

17

_____ is typically indicative of necrosis

Pyknosis (Loss of nuclear integrity)

18

Two key features of necrosis

1. Inability to reverse mitochondrial dysfunction
2. Disruption of membranes leading to dissolution of cell

19

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

20

Cytoplasmic changes associated with necrosis?

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

21

Three main types of nuclear changes associated with necrosis

Pyknosis, Keryorrhexis, Karyolysis

22

Describes pyknosis

Solid, shrunken basophilic mass
Increased basophilia of chromatin

23

Describe karyorrhexis

Pyknotic nucleus undergoes fragmentation

24

Describe karyolysis

Dissolving of nucleus into amorphic mass

25

Describe coagulative necrosis

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

26

Describe liquefactive necrosis

Large neutrophil infiltration, architecture destroyed
Soft/Liquid Mass, Capsule

27

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.

28

Exception to the rule on liquefactive?

Happens in brain necrosis, may have no PMN infiltrate

29

What is gangrenous necrosis?

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

30

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.

31

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

32

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

Eosinophilic ghost outlines of necrotic adipocytes
Basophilic Ca deposits
Inflammation