Irreversible Cell Injury and Cell death Flashcards
What determines the cellular response of injury?
(1) the type of cell,
(2) the severity
(3) the duration
What cell is the most susceptible to hypoxia?
Neurons (3-5 minutes)
What are the cells that are susceptible to hypoxia within 30 minutes to 2 hours?
Myocardium, hepatocytes, renal epithelium
What are the cells that are susceptible to hypoxia many hours later?
Fibroblasts, epidermis, skeletal muscle
What is Oncotic necrosis?
Pathologic.
Swelling ( and damage from swelling) due to increased sodium and increased H2O in cell.
What is Apoptosis?
Physiologic cell (point of no return) death/Programmed cell death Considered Physiologic and Pathologic
What are the 3 points of no return in cell injury?
- Increased mitochondrial damage.
- Increased Cell Membrane Permeability
- Increased Calcium
What are the ultrastructural indications of oncotic necrosis?
- Swelling
- Rupture of plasma membrane and organelles ( leakage of contents which attracts inflammatory cells)
- rupture of nucleus
- Swollen Mitochondria and develop amorphous densities
What are the microscopic indications of oncotic necrosis?
- Hypereosinophilic cytoplasm ( due to denatured protiens and loss of ribosomes)
- Nuclear Changes:
Pyknosis (nuclear condensation with shrinkage and intense basophilia) - Karyorrhexis (nuclear fragmentation)
- Karyolysis ( nuclear dissolution or loss)
What nuclear change is occuring in this image?
- Pyknosis (nuclear condensation with shrinkage and intense basophilia)
What nuclear change is occuring in this image?
Karyorrhexis (nuclear fragmentation)
What nuclear change is occuring in this image?
Karyolysis (nuclear dissolution or loss)
What is occuring at letters A-C in this histological image?
A.) Pyknosis
B.) Karyorrhexis
C.) Karyolysis
What is occuring to the cells in this image?
Necrotic neurons with hypereosinophilic cytoplasm and pyknotic nuclei
What is occuring in this image?
Nuclear karyorrhexis
What can be seen in gross observation of cells with oncotic necrosis?
- Swelling and pallor (soon after death)
- Loss of structural detail and demarcation from adjacent viable tissue.
- Discolored (usually white)
- Soft
Varies alot and dependent on tissues involved, time between death and necropsy, and nature of injurious agent.
What are the classifications of necrosis?
Coagulative
Caseous
Liquefactive
What is important to remember about types of necrosis/
The morphologic appearance of necrotic cells and tissues changes
with time.
Coagulative necrosis → Liquefactive necrosis
What are the causes of coagulative necrosis?
hypoxia, ischemia, or toxic injury
What are observational indications that would infer the section is of coagulative necrosis?
- General tissue architecture preserved
- Cell outlines still recognizable
- Pale tan to pale gray (it can be red, hemorrhagic: hemorrhagic infarct and venous infarct)
- Often sharply demarcated from the adjacent viable tissue
• Solid (without apparent crumbling, sloughing, liquefaction, or other obvious loss of
structure)
What is an infarct? What kind of necrosis can this be seen in?
Infarct: a focal area of coagulative necrosis resulting from failure of blood supply (ischemia)
What is a hemmorrhagic infarct?
Blood enters the infarcted tissue because blood flow restored in the obstructed
vessel or arrived from collateral circulation
What is an ischemic infarct?
After a few days macrophages remove the blood from acute hemorrhagic infarct
What is a venous infarct?
infarct when vein is occluded due to some sort of compression
i.e strangulating lipoma, small intestinal volvulus
What is a strangulating lipoma? What animal is it more common in?
It is a lipoma that causes a section of intestine to loose blood supply. This occurs in horses.
What is occuring in this image? What would be the characteristic that indicates what is going on?
Toxic injury. The pale color to the tissue.
What is occuring in this image?
Toxic Injury
- There is prominent lobular pattern
What is ocurring in this histological section? What does it indicate?
- Eosinophillic staining + Nuclei loss or Pyknosis.
There are preservation of cell outlines though.
Coagulative Necrosis.
What is occuring in this image? What are the two lines drawn to?
Coagulative necrosis. You can see preservation of tissue architecture. The arrow on the right side is indicating the dead tissue while the arrow on the right is indicating live tissue.
What is occuring in this image?
Necrotic myofibers
What is caseous necrosis?
curdled cheese like gross appearence. Older lesion with complete loss of cellular or tissue architecture. Cell outlines are not visible. Granular to amorphus eosinophilic substance with basophilic nuclear debris. Mineralization occurs.
What does caseous necrosis look like grossly?
Granular, Friable Consistancy (Loss of tissue architecture)
Looks like cheese
Why are caseous necrosis not diffuse lesions?
This is because of granuloma formation and the body attempting to wall off the infection.
What is occuring in this image? Please label the arrows
Caseous necrosis.
Top arrow -> granuloma formation ( inflammation trying to wall off infection)
Bottom arrow -> area of necrosis
What is occuring in these images?
Eosinophillic granular substance in light pink areas
bottom arrow is mineralization.
What is liquefactive necrosis?
Necrotic tissue converted into fluid phase.
Cells are lysed by lytic enzymes of neutrophils
Yellow/ soft consistency ( pus like fluid)
What is an abcess?
Collection of dead neutrophils
What is occuring in this image, why?
Cells lysed by lytic enzymes.
Lack of fiberous tissue to uphold structure.
What is Malacia?
Term of gross appearance of necrosis in the CNS
What can be found at the center of an abcess?
Pyogenic bacteria
What can you see microscopically with Liquefactive necrosis?
- Loss of tissue and cellular structure
- Cells outlines are not visible
- Granular to amorphous eosinophilic substance with basophilic nuclear debris
- Numerous viable and necrotic neutrophils (in abscesses)
What is occuring in this image? What is the circled area indicating?
Liquefactive necrosis
- Circle: Malecia
What is occuring in this image of white matter within the CNS?
Liquefactive necrosis
- Loss of neuropil (rarefaction)
- Loss of tissue and cellular structure
- Eosinophilic amorphous material
What is Gangrenous necrosis? How can you tell the difference between the two types of gangrene?
Dry gangrene
- coagulative necrosis - due to loss of blood supply
- At the distal aspect of extremities: limbs, tail, or pinnae
- Imparts a dry, leathery texture
- *- Free of bacteria**
Wet gangrene
- Necrotic tissue invaded by bacteria
- Occurs commonly in the lungs (aspiration pneumonia) and mammary glands
- If bacteria are gas forming (Clostridium spp.): Gas gangrene
What kind of gangrene is seen in this image?
Dry gangrene
What kind of gangrene can be seen in this image? What is its cause?
Wet Gangrene: Aspiration pneumonia: Ruminal (stomach content) rich in bacteria
What is occuring in this image?
Gangrenous mastitis
Wet gangrene
What are the 3 types of fat necrosis?
- Enzymatic
- Traumatic
- Idiopathic
What is enzymatic fat necrosis?
Occurs secondary to leakage of pancreatic enzymes (lipases) in cases of pancreatitis
What is traumatic fat necrosis?
• Blunt trauma or chronic pressure against bony prominences
(subcutaneous adipose tissue in recumbent animals (I.e liposuction)
What is idiopathic fat necrosis?
• Necrosis of abdominal fat in overconditioned cattle
Cause unknown
What is occuring in this image?
Enzymatic fat necrosis
What type of fat necrosis is shown in this image? What is one concern/consequence of this kind of fat necrosis?
Idiopathic, can cause an obstruction
What are the terms associated with necrosis of epithelium? What does each term mean?
Erosion: Suprficial sloughing or exfoliation of dead cells without rupture of basement membrane.
Ulcer: Full thickness necrosis of epithelium ( with rupture of basement membrane)
What is occuring in this image?
Ulcers
What is occuring in this image? What can this cause?
Perforating ulcer. This can cause peritonitis due to leaking of GI contents.
What is the sequelae to oncotic necrosis?
- Inflammatory reaction
- Sequestrum ( separation because foreign material cannot be digested so it is walled off)
- Regeneration ( due to inflammation)
- Scar formation ( replacement of necrotic tissue by fiberous connective tissue)
What cells will go to the site of necrosis?
Neutrophills and macrophages
What is occuring when a red line encircles the necrotic tissue?
Red line encircles the necrotic tissue = vessels bringing leucocytes to the site • Neutrophils and macrophages phagocytize the necrotic tissue
What is occuring in this image? Why?
Sequestrum
Piece of dead bone that has become separated during the process of necrosis from normal bone (sequela of chronic osteomyelitis)
What is occuring in this image? What allows for the changes seen in the second photo?
Inflammation with regeneration. After stimulus is removed, comlpete regrowth. This occurs if defect is shallow enough.
What is occuring in this image?
This is inflammation with scar formation. Chronic area is being filled in and contraction of fiberous connective tissue.
What is a scar?
scar: replacement of dead tissue by fibrous connective tissue
What is apoptosis?
Apoptosis (apoptotic necrosis) is a type of programmed cell death with initiation
of a self-induced cell death process (“cell suicide”)
It is both, physiologic and pathalogic and is morphologically characterized by condensation and shrinkage of cell.
What is the physiologic triggers of apoptosis?
• Physiologic:
- Programmed cell destruction during embryogenesis
- Involution of organs or tissues deprived of hormonal stimulation (endometrial and uterine involution)
- Cell deletion in proliferating cell populations (to keep homeostasis). Epithelial cells of the skin, gut, etc..
What is occuring in this image? and what is this caused by?
Syndactyl
This is failure of apoptosis
What are the pathologic triggers of apoptosis?
• Pathologic triggers of apoptosis:
- Injury from toxins, ROS
- Mitochondria and DNA damage (radiation, anticancer drugs)
- Mediated by cytotoxic T lymphocytes and NK cells
- Nutrient deprivatio
What regulates apoptotis?
*** regulated by pro-apoptic and anti-apoptotic intracellular proteins*** **** that activate gene and enzymes leading to cell death****
What occurs to the cell during necrosis? What occurs during apoptosis?
Necrosis: Swelling leads to rupture which allows for leakage ( Necrosis always induces inflammatory response due to the content release (leakage of enzymes) stimulating inflammatory cells to come of site of leak. )
Apoptosis: is programmed cell death. Shrinkage of cell. Condensation/ Fragmentation of cell but is surrounded by plasma membrane, so there is no inflammatory reaction. These cell fragments will become phagocytized.
