DD 1 Flashcards
Give 3 examples of PMNs
Neutrophils
Basophils (related to mast cells)
Eosinophils
3 examples of Mononuclear cells
Leukocytes
Monocytes
Lymphocytes
In acute injuries, are PMNs or mononuclear cells more involved?
PMNs
- produce effect in seconds/minutes
In chronic injuries, are PMNs or mononuclear cells more involved?
Mononuclear - (lymphocytes, macrophages, leukocytes)
- ongoing injury
What are oxygen free radicals?
chemical species w/ unpaired electron
How do oxygen free radicals arise?
H2O2 in the presence of superoxide anion O2- can lead to oxygen free radicals
- generated by too much O2 during O2 poor conditions via intrinsic oxidases and radiation
How do oxygen free radicals produce cellular injury?
highly reactive → random oxygen atoms oxidizing (pulling e-) from a variety of things inside cell
How does the body get rid of oxygen free radicals?
Via either one of 2 catalases:
- Superoxide anion, O2- → broken down to H2O2 → broken down by glutathione peroxidase (antioxidant)
- Oxygen free radicals can also be removed by superoxide dismutase (SOD)
or
Antioxidants (uric acid, Vit E)
Where can intrinsic oxidases that generate oxygen radicals be found?
ER of all cells and in PMNs
How does ischemia/hypoxia create setting where Oxygen free radical damage causes cell injury
Hypoxia → ischemic injury → Induces txn factor: hypoxia-inducible factor 1 (HIF1 α/β) → Targets genes (EPO, VEGF, glucose transporters, glycolytic enzymes)→ increases ROS
Single most important type of injury seen in clinical medicine
Other than cell’s inability to make enough ATP to maintain viability, cell can also produce oxygen radicals.
3 ways clinical medicine can produce oxygen radicals
- O2 therapy
- Acute inflammation
- Reperfusion
During acute inflammation, which cells have enzymes that can produce oxygen radicals?
-name that enzyme
PMNs
- myeloperoxidase
*hypoxic tissues are infiltrated by PMNs remember?
What is reperfusion?
restoring flow of blood to organ/tissue after period of ischemia or hypoxia
How can reperfusion (restoring flow of blood to organ/tissue) cause oxygen radicals?
In prolonged ischemia → hypoxanthine is formed via ATP metabolism break down → give back oxygen →Xanthine dehydrogenase is converted to xanthine oxidase → so when you do give them O2→ produces oxygen radicals
Which cell death, Necrosis or apoptosis is usually seen in:
ischemia or w/ toxins/chemicals?
With this in mind, would it lead to large or scattered areas of cells dying?
Necrosis
-large area: cells die simultaneously
Which cell death, Necrosis or apoptosis is usually seen in:
elevation in intracellular [Ca2+]?
how does death occur?
Necrosis
Ca2+ leaks into cell and Ca2+ storage in ER and mitochondria is released → activates Ca2+ dependent proteases and lipases → cytoplasm dead and swollen → loss in membrane integrity
Name 3 ways that Apoptosis is regulated
via:
Ligands + cell surface receptors ( Fas ligand)
Mitochondria activation of caspase (Apoptosis inducing factor AIF)
Nuclear DNA endonuclease
coagulative necrosis
What is it?
Example
dead cell remnant “ghost like”
-ie: heart following MI
What are three characteristics that you see in smears regarding coagulative necrosis?
more eosinophilic, nucleus shrinks, clumped chromatin deeply basophilic (pyknotic),
fragmented nucleus (karyorrhexis), dark condense (pyknotic) clumps break down and disappear (karyolysis)
Liquifactive necrosis
What is it?
Example
Dead cell dissolves - lysosomal hydrolases digest cell compartments
Common in: brain + spleen w/ acute infection
Caseous necrosis
What is it?
Example
Central portion of infected lymph node is necrotic
Chalky white (like milk casein)
Only in tuberculosis
Fat necrosis
What is it?
Example
Necrotic adipose tissue - fats are hydrolyzed into free fatty acids → ppt with Ca2+ →chalky gray material
Common in acute pancreatitis or trauma
Reversible biochemical alterations during hypoxic injury
1) ↓ ATP
2) ↓ Na pump (cell swelling)
3) ↑ glycolysis,
4) ↓ pH
5) ↓ protein synthesis
