34 terms

Reversible Cell Injury

Lecture 6
What are the 2 types of cell injury?
*Reversible cell injury
*Irreversible cell injury
What is reversible cell injury?
*It is reversible up to a certain point
*Alteration of homeostasis
*Recovery and return to normal when the stressor or injurious stimuli are removed
What are the morphological correlates of reversible cell injury?
*Cellular swelling
*Fatty changes
When is cell injury irreversible cell injury and cell death?
If the injurious stimulus persists or it is severe enough (at first) that the cell passes a "point of no return"
What are the morphologic correlates of irreversible cell injury?
What is another name for acute cell swelling?
Hydropic degeneration
What is the definition of acute cell swelling?
*Early, sub-lethal manifestation of cell damage, characterized by increase cell size and volume
*(Sub-lethal because the cell is still alive)
*Most common and fundamental expression of cell injury
What is the pathogenesis of acute cell swelling due to hypoxia?
Hypoxia -->
ATP production decrease -->
Na and H2O move into cell and K moves out of the cell -->
Osmotic pressure increase -->
More water moves into cell -->
Cisternae of endoplasmic reticulum distend, rupture and form vacuoles -->
Hydropic degeneration
What is the etiology of acute cellular swelling?
Any entity capable of disrupting cellular homeostasis
Give examples of the etiology of acute cellular swelling
*Physical, mechanical injury
*Toxic agents
*Free radicals
*Viral organisms
*Bacterial organisms
*Immune-mediated injury
What is the gross appearance of acute cellular swelling?
*Slightly swollen organ with rounded edges
*Pallor when compared to normal
*Cut surface: tissue bulges and can not be easily put in correct apposition
*Slightly heavy
*Changes in reticular pattern dependent on species
What is the histologic appearance of acute cellular swelling?
*Water uptake dilates the cytoplasm
*Cells are enlarged with pale cytoplasm
*Nucleus in normal position
What is the light microscopic appearance of acute cell swelling?
*Represents distended and pinched-off segments of ER
*Nucleus is still present, but the cytoplasm is pale
What is ballooning degeneration?
*Same as hydropic degeneration only in the epidermis of the skin
*Once the epidermis can no longer hold so much fluid, the cells rupture and fused to form a "balloon," like a blister
Which types of cells are highly vulnerable to hypoxia and cell swelling?
*Proximal renal tubule epithelium
*CNS neurons, oligodendrocytes, astrocytes (cytotoxic edema)
What is the difference between hydropic degeneration and hypertrophy?
*Hydropic degeneration - cell swelling is due to increase uptake of H2O and then to diffuse disintegration of organelles and cytoplasmic proteins
*Hypertrophy - the cell enlargement is caused by increase of normal organelles
What are the ultra-structural (EM) changes of acute cellular swelling due to ischemia?
*Loss of microvilli
*Blebs have formed and extruded in the lumen
*Mitcohondria would have been swollen during ischemia; with reperfusion, they rapidly undergo condensation and become electron-dense
What are the ultrastructural (EM) changes of acute cell swelling?
*Cell swelling with dilation of endoplasmic reticulum (ER)
*Detachment of ribosomes from the rough ER, dissociation of polysomes
*Loss of surface structures (such as microvilli and cilia)
*Breakdown of inter-cellular attachments
*Membrane blebs, myelin figures
*Mitochondrial changes: low-amplitude swelling and early high-amplitude swelling, loss of dense matrix granules, loss of sequestered Ca ions, possible deposition of calcium salts
*Chromatin clumping
What are myelin figures?
Phospholipid aggregates in the cytoplasm due to phospholipase activity on organelle membranes
What is low-amplitude swelling?
Contraction of the inner compartment and expansion of outer compartment
What does the prognosis of cellular swelling depend on?
How much of the cell is affected and how long it's been affected
*Good or Poor
*Poor prognosis = if there is lysis of affected cells then irreversible injury will occur
What is fatty change?
Sub-lethal cell damage characterized by intracytoplasmic fatty vacuolation
Fatty change may be preceded or accompanied by cell swelling
In what cells do fatty changes occur?
*In cells participating in fat metabolism (hepatocytes)
*Renal tubular epithelium
Why does fatty changes occur in hepatocytes?
Because decrease protein synthesis leads to decrease lipid transport out of hepatocytes
What type of stain is used to tell if a cell is swollen due to fat or water?
*Oil Red O
*Fat will stain red, water doesn't stain
What is the basic mechanism of the pathogenesis of fatty change?
*Impaired metabolism of fatty acids -->
*Leading to accumulation of triglycerdes -->
*Formation of intracyoplasmic fat vacuoles
What are the stages in the pathogenesis of fatty change?
*Lipids enter hepatocytes as FFA
*Fatty acids can also be synthesized from acetate
*FFAs are esterified to form triglycerides
*Triglycerides are complexed with apoproteins to form lipoporteins
*Lipoproetins are the only form in which triglycerides can be transported out of hepatocytes
*Lipids are processed by hepatocytes and exported from hepatocytes
*Accumulation of intracellular lipid can occur due to abnormalities in any of these steps
What are all the possible outcomes of FFA?
*Utilized in synthesis of cholesterol
*Utilized in synthesis of phospholipids
*Degraded/oxidized to become ketone bodies
*Esterified to form triglycerides
What are the mechanisms for fatty degeneration?
*Excessive delivery of free fatty acids from the gut or from adipose tissue
*Decreased beta-oxidation of fatty acids to ketones & other substances because of mitochondrial injury (toxicity, hypoxia)
*Impaired synthesis of apoprotein (starvation, CCl4 toxicity, aflatoxicosis)
*Impaired combination of triglycerides & proteins to form lipoprotein
*Impaired release (secretion) of lipoproteins from the hepatocyte
What are the etiologies for fatty change?
*Main causes: hypoxia, toxicity and metabolic disorders
*Seen in abnormalities of synthesis, utilization &/or mobilization of fat
What is the gross appearance of fatty change?
*Liver: diffuse yellow (if all cells are affected)
*Enhanced reticular pattern if specific zones of hepatocytes are affected
*Edges are rounded and will bulge on section
*Tissue is soft, often friable, cuts easily and has a grease texture
*If condition is severe small liver section may float in fixative or water
Which species have probability of fatty liver?
*Ruminants (cattle)
*Occasionally horses
What is the histologic appearance of fatty change?
*Well delineated, lipid-filled vacuoles in the cytoplasm
*Vacuoles are single to multiple, either small or large
*Vacuoles may displace the cell nucleus to the periphery
*Granular or feathery changes to cytoplasm
*Cytoplasm becomes vacuolated with smooth, clear edges and nucleus is pushed to the side