Pathology - Injury, death, and adaptation Flashcards
2 ways a cell can die
necrosis and adoptosis
What causes cell injury?
Victorian
V-Vascular
Infectious
CHemical
Trauma-Temperature
Ospital
Radiation
Inhereted
Autoimmune
Nutritional
The cellular responsae to injury depends on the:
- Severity/intensity/duration & nature of the injurious agent
- the nature and genetic background of the cell
What is a reversible cell injury
Change in function and cellular moirphology in response to an injurious agent that return to normal after removal of the injurious agent
Macroscopic (gross findings) findings when reversible cell injured?
- increased organ weight
- pale with increased turgor (swollen)
Light microscopic findings when reversible cell injury
-Cellular swelling
-Blebbing of plasma membrane
-Hydropic change/vacuolar degeneration
-Fatty change
Ultrastructural (electron microscopy) findings when reversible injured cell
- Plasma membrane damage
- Mitochondrial swelling
- Dilatation of endoplasmic reticulum
- Detachment of ribosomes
/
What happens on the right picture? What are we seeing on the left one?
Surface blebbing, eosinophilia, and cell swelling
- left one: normal renal tubules
What is necrosis
Necrosis: Pathologic rapid, uncontrollable cell death in response to severe or persistent injury
macroscopic (gross) patterns of necrosis (high yield) (5)
- Coagulative necrosis
- Liquefactive necrosis
- Caseous Necrosis
- Fat necrosis
- Fibrinoid Necrosis
Findings in coagulative necrosis
- cellular outline is maintained
- protein degradation
Liquefactive necrosis findings
- loss of cellular outlines
- enzymatic digestion and inflammation (pus)
Caseous necrosis findings
- special type of necrosis in mycobacterial infection
- amorphous granular debris surrounded by granulomatous inflammation
Fat necrosis findinds
- fat destroyed through action of lipases
- grossly appears as chalky areas
Looks pale pink, with a rim of blood. in liquifactive necrosis there is a lot of blue - in coagul
what kind of necrosis
what kind of necrosis
liqufactive necrosis
What kind of necrosis
on the left: cheese like necrosis - lymph node with caseous necrosis
on the right: necrotizing granulomas
(its a lymph node, but no way to figure out what it is0 what kind of necrosis?
Caseous Necrosis
With granulomatis inflammation = macrophages inflammation
What kind of necrosis
Fat necrosis
Light Microscopy findings – Cytoplasmic Changes when necrosis
Increased eosinophilia
Hyaline Change
Vacuolation
Calcification
Light Microscopy findings – Nuclear Changes when necrosis
- Karyolysis : loss of basophilia due to breakdown of DNA
- Karyorrhexis : nuclear fragmentation
- Pyknosis - shrinkage of the nucleous and increased basophilia due to DNA condensation
- Complete loss of nucleus
Definition of aptotosis
Programmed cell death involved in both pathologic and physiologic processes
Example of physiologic apoptosis
-Embryogenesis
-Involution of hormone dependent tissues
-Homeostasis in proliferating cell populations
-Elimination of self-reactive lymphocytes
-Destruction of inflammatory cells after they are no longer needed
Examples of pathological apoptosis
-DNA damage (radiation, hypoxia, cytotoxic agents)
-Misfolded protein response
-Induced by virus or host response
-Pathologic atrophy
2 pathways that leads to apoptosis
- Mitochondrial (intrinsic) pathway
- Death receptor (extrinsic) pathway
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Slide 30
Morphologic features of apoptosis
- Cell shrinkage
- chromatin condensation
- Blebbing, fragmentation, and formation of apoptotic bodies
- Phagocytosis of apoptotic bodies
example of failure of physiologic apoptosis during development
Fraser syndrome : The digits have failed to separate in a case of Fraser syndrome, an autosomal recessive disorder associated with defects in genes involved in apoptosis.
What happens with ATP in the case of Necrosis vs Apoptosis
Necrosis: Independent
Apoptosis: Dependent
What happens with cell sinze in the case of Necrosis vs Apoptosis
What happens with the nucleus in the case of Necrosis vs Apoptosis
What happens with Plasma membrane in the case of Necrosis vs Apoptosis
What happens with cell content in the case of Necrosis vs Apoptosis
What happens with inflammation in the case of Necrosis vs Apoptosis
Physiologic or pathologic in the case of Necrosis vs Apoptosis ?
Necrosis: Always pathologic
apoptosis: both
On what depends the damage caused by a particular injurious agent on the cell ? (3)
- Nature of the injury – Severity & Duration
- Type of cell, it’s metabolic state, adaptability, and genetic makeup.
- Damage is usually caused because of interference in multiple biochemical processes
Principle mechanisms and sites of cell injury (4)
- Hypoxia/ischemia, radiation and other injurious agents on the mitochondria
- ROS or other injurious agents that damages the cellular membranes
- Radiation or mutations that affects the nucleus
- Mutations, cell stress or infections that affects the endoplasmic reticulum
definition of hypoxia
Oxygen deprivation (anaerobic glycolysis can continue since substrates continue to be delivered).
Definition of ischemia
Oxygen deprivation and diminished blood flow (affects aerobic and anaerobic energy production)
definition of reperfusion injury
Paradoxical increase in cell injury after blood flow is returned to an ischemic area (complex but likely related to increased generation of ROS, influx of calcium, and activation of leucocytes)
Definition of hypertophy
Increased Synthesis of Cell Structural Components
Where does hypertrophy happens?
Occurs in Dividing and Non-Dividing Cells
-Increased functional demand
-Hormonal Stimulation
Is hypertrophy physio or patho?
both
Mechanisms – Mechanical or trophic factor of hypertrophy (2)
- Increased protein synthesis
- Re-expression of developmental genes
- Induction of structural genes
What is hyperplasia?
Increase in cell number
By what is caused hyperplasia?
Caused by stress or noxious stimuli leading cells with proliferative capacity to divide (less commonly stem cells)
Os hyperplasia patho or physio?
Both
Mechanisms of hyperplasia
- Growth Factors/Hormones
- Growth Receptors
- Activation of Signaling Pathways
- Activation of Cell Cycle Regulators
- New production from stem cells
What is metaplasia
replacement of one cell type by another
Is metaplasia patho?
Always
By what is caused metaplasia?
Caused by:
- chronic inflammation
- cytostatic druges
What is the mechanism of metaplasia?
reprogramming of stem celles or undifferentiated cells
2 types of pathologic calcification
- dystrophic calcification
- Metastatic calcification
where does dystrophic calcification occurs?
Occurs at sites of previous necrosis
What is the apperance of dystrophic calcification
Appears as clumped, amorphous basophilic material
Pathogenesis of dystrophic calcification
Calcium is concentrated in membrane-bound vesicles in cells with membrane damage.
when does metastatic calcification occurs?
Occurs in setting of hypercalcemia
Causes of hypercalcification?
- Parathyroid hormone (bone reabsorption)
- Destruction of bone secondary to malignancy
- Vitamin D disorders
- Renal Failure (secondary hyperparathyroidism)
