Chapter 2 (Sections 1 and 2) - Cell Responses Flashcards
4 things in a cascade that are the disease process overview
- Etiology - cause of disease
- Pathogenesis - sequence of cellular events
- Morphologic Changes - structural alterations in cells
- Clinical Manifestations - signs and symptoms of disease
2 broad classes of causes of disease
- Genetic
2. Environmental
Any deviation from normal structure or function and is manifested by characteristic symptoms
Disease
A derangement or abnormality of function
Disorder
Any new or abnormal growth
Neoplasm
A set of symptoms that occur together
Syndrome
Adaptation of a cell
Reversible functional and structural responses to changes that allow the cell to achieve a new steady state to survive and continue functioning
If a cell is unable to adapt, what will occur?
Cell injury
Is a cell injury reversible?
Yes, up to a certain point and then it becomes an irreversible injury
What changes are seen in a cell with a reversible injury?
Swelling and fatty changes
If a cell suffers irreversible injury, what will occur?
Cell death
List some causes of cell injury
Oxygen Deprivation
Physical agents (stress)
Chemical agents - ex. drugs
Infectious agents - ex. parasite
Genetic mutations
Nutritional imbalances - ex. protein-calorie deficiency
Immunologic reactions - ex. autoimmune rxns
Is there a time lag between the stress applied to the cell and the morphologic changes of the cell injury?
Yes
With a cell that is undergoing necrosis, the morphologic changes may not be seen for several hours after injury. However, what can be measured much sooner and why?
Specific enzymes and biomarkers released from the cell due to loss of plasma membrane integrity during necrosis!!
What 2 phenomena characterize the point of no return for irreversible cell injury?
- Mitochondrial damage with ATP DEPLETION
2. Lysosomal and plasma membrane rupture
For cell death, what are the options?
Necrosis
Apoptosis
Necrosis and Apoptosis - Cell size
Necrosis = Enlarged and swollen Apoptosis = Shrinkage and chromatin condensation
Necrosis and Apoptosis - Plasma membrane
Necrosis = DISRUPTED plasma membrane Apoptosis = INTACT plasma membrane with blebbing
Necrosis and Apoptosis - Cell content release
Necrosis = Digested enzymes and contents leak out disrupted plasma membrane Apoptosis = Cellular contents can be released in apoptotic bodies
Necrosis and Apoptosis - Adjacent inflammation
Necrosis = YES Apoptosis = NO
Why is there no adjacent inflammation with apoptosis?
The cell is devoured by macrophages before the contents can leak out and cause an immune response
List 3 nucleus changes seen with Necrosis
- Karyolysis
- Pyknosis
- Karyorrhexis
Karyolysis
Nuclear fading
- seen with necrosis
Pyknosis
Nuclear shrinking
- seen with necrosis
Karyorrhexis
Nuclear fragmentation
- seen with necrosis
How do necrotic cells appear on a stain?
Increased cytoplasmic Eosinophilia (pink)
Necrosis and Apoptosis - Pathologic or Physiologic?
Necrosis = Pathologic Apoptosis = Physiologic or Pathologic
Common things that leak out of necrotic cells?
ATP and Uric Acid
Coagulative Necrosis
Dead tissue is preserved for a few days due to proteolysis of dead cells being blocked
- Ischemia of a vessel can cause this
Liquefactive Necrosis
Digestion of dead cells creates a viscous liquid (pus)
- Focal bacteria in the BRAIN may lead to this
Gangrenous Necrosis
Loss of blood supply to a limb; seen in diabetes
Caseous Necrosis
Yellow-white “cheesy” appearance to necrotic area
- Tuberculosis infection of the lungs can cause this
Fat Necrosis
Fat destruction due to pancreatic lipases;
White chalky deposits are seen
Fibrinoid Necrosis
Antigen-Antibody complexes deposited in blood vessel walls that appear more pink (eosinophilic)
- Vascular damage during immune reactions cause this
Tightly regulated cell death; cell activates its own enzymes to degrade itself and its contents
Apoptosis
Physiologic causes of Apoptosis
Eliminating cells no longer needed
- ex. Development, menstrual cycle
Elimination of self reactive Lymphocytes uses what mechanism?
Apoptosis – Extrinsic pathway
Pathologic causes of Apoptosis
Eliminating cells that are injured beyond repair
- ex. DNA damage, misfolded proteins, viral infection
What enzymes become activated with Apoptosis?
Caspases
2 pathways for Apoptosis?
- Mitochondrial pathway (intrinsic) - Most common!
2. Extrinsic pathway (Death receptor initiated)
Job and example of Anti-Apoptotic molecules?
Keep the outer mitochondrial membrane IMPERMEABLE
- ex. BCL-2
Job and examples of Pro-Apoptotic molecules?
Increase permeability of the outer mitochondrial membrane
- ex. Bak and Bax
With Apoptosis, once the Pro-Apoptotic molecules increase the permeability of the outer mitochondrial membrane, what is released from there into the cytosol?
Cytochrome C
For the Mitochondrial pathway of Apoptosis, what activates Caspase 9 in the cytosol?
Cytochrome C
Apoptosome
Cytochrome C + APAF-1 in the cytosol
= Activates Caspase 9!
For the Extrinsic pathway of Apoptosis, what receptors are activated?
FAS
TNF
Once FAS and TNF receptors are activated with the Extrinsic pathway of Apoptosis, what happens next?
- Activates Caspase 8 which activates Caspase 9
What can inhibit the Extrinsic pathway of Apoptosis?
FLIP - binds the Pro-Caspase 8 so it cannot be cleaved and activated
Autophagy
Cell eats its own contents
When is Autophagy usually present?
Nutrient Deprivation
Describe the order of events with Autophagy
- Sequestration of organelles
- Creation of an Autophagosome
- Autophagosome fuses with lysosomes
- Lysosomes degrade Autophagosome contents
= Contents are recycled!
What is an example of a disease state that dysregulation of autophagy might occur?
Inflammatory bowel disease, Cancer
Pyroptosis occurs in cells that are infected with?
Microbes
Pyroptosis
Programmed cell death; Caspase 1 activated
Caspase 1 causes IL-1 release and Fever
Necroptosis
Programmed Necrosis; NO CASPASES
- Release of cellular contents and evokes inflammation
What triggers Necroptosis by ligations?
TNFR1
What form holes in the plasma membrane with Necroptosis?
RIPK and MLKL
