necrosis and apoptosis - work load adaptation

lecture 6

Cellular swelling is one of the most common and basic signs of cell

injury. Which specific process causes this event?

a.) Multiplication of mitochondria due to increased demands on the cell.

b.) Storage of pigment in cells.

c.) Loss of Na+/K+ ATPase function

c.) Loss of Na+/K+ ATPase function

for coagulation necrosis, the outline of the cell persists because there is denaturation of protein ncluding enzymes, thus

self digestion via these enzymes cannot occur and the cellular components are not dissolved until the arrival of inflammatory cells

cytoplasmic changes in dead cells involve

• loss of differential staining of nucleus and cytoplasm (hypereosinophilic)

• swelling with fragmentation

• loss of cell to cell contact

• loss of microvilli and cilia

which side is exhibiting necrotic hepatocytes?

left side

liquefactive necrosis occurs when

enzymatic digestion of necrotic cells predominates

for liquefactive necrosis in bacterial infections, neutrophils contain

potent hydrolases

liquefactive necrosis occurs in hypoxic damage of the

CNS

what is the gross appearance of liquefactive necrosis?

soft, viscous, fluid mass

in acute inflammation, liquid is mostly dead WBC (pus)

what is the microscopic appearance of liquefactive necrosis?

may see degenerate neutrophils and/or amorphous necrotic material

(or nothing if necrotic tissue has flowed out)

caseous necrosis is seen with specific bacterial diseases like

tuberculosis, caseous lymphadenitis

what is the gross appearance of caseous necrosis?

grey-white, dry (inspissated),

friable to pasty necrotic material

cheese like

frequently with dystrophic calcification

with the microscopic appearance of caseous necrosis, dead cells persist as

amorphous, coarsely, granular eosinophilic debris

with the microscopic appearance of caseous necrosis, necrotic cells do not

• retain cellular outline

• undergo complete dissolution

the microscopic appearance of caseous necrosis is frequently associated with

granulomatous inflammation and thick outer fibrous capsule

gangrenous necrosis is defined as

ischemic necrosis of extremities, such as limbs, digits, or tips of ears

what are examples of gangrenous inflammation

aspiration pneumonia and gangrenous mastitis

dry gangrene

coagulation of necrosis of an extremity with subsequent mummification

wet gangrene

when the coagulative necrosis of dry gangrene is modifidied by the liquefactive action of saprophytic/putrefactive bacteria

gas (emphysematous) gangrene

clostridial infections with necrosis and gas production

eg C. chauvoei (blackleg)

fact necrosis is distinguished by its

location in body fat stores

what is the etiology of fat necrosis

inflammation, vit E deficiency, trauma, idiopathic

what is the gross appearance of fat necrosis

firm to hard, white/chaky ± gritty area (oftens adjacent to normal fat - saponification)

what is the microscopic appearance of fat necrosis

often see basophilic calcium deposits and often surrounded by inflammatory cells

is necrosis or apoptosis active (1)

apoptosis (1)

does necrosis or apoptosis have a tissue respone (2)

necrosis (2)

necrosis causes ______ ______, while apoptosis causes _____ ______-

membrane injury

DNA damage

between necrosis and apoptosis, which one does not have mitochondrial and ER changes (3)

apoptosis (3)

between necrosis and apptosis, which has blebbing only? (4)

apoptosis (4)

does necrosis or apoptosis have karyolysis (5)

necrosis (5)

apoptosis lacks which one

1. pyknosis

2. karyorrhexis

3. karyolysis

karyolysis

apoptosis will have ______ cytoplasmic eosinophila

increased

apoptosis results in the formation of

apoptotic bodies

what are apoptotic bodies

cell fragments bounded by plasma membrane containing normal organelles and condensed nuclear fragments

what are the 5 causes of apoptosis?

1. cell death during embryogenesis

2. normal turnover

3. immune system

4. cell death in neoplasm

5. pathogenic stimuli

What are examples of normal turnover that causes apoptosis?

1. hormone dependent involution

2. cell deletion in proliferating population

What are examples of the immune system causing apoptosis?

• deletion of autoreactive T cell clones in thymus

• cell death of cytokine-starved lymphocytes

• cell death induced by cytotoxic T cells

what are examples of pathogenic stimuli that cause apoptosis?

• some viruses and immune-mediated processes

• radiation/drugs damaging DNA

• low doses of toxins/drugs, hyperthermia, hypoxia

what is the morphology of apoptosis

cell shrinkage

chromatin condensation

cytoplasmic blebs → apoptotic bodies

phagocytosis of apoptotic bodies

who performs phagocytosis of apoptotic bodies

macrophages with no inflammation

erythema multiforme is defined as the

Acute reaction pattern of the skin and mucous membranes that may be

elicited by a wide array of trigger factors

even though the pathogenesis of erythema multiforme is incompletely understood, what is the hypothesis?

EM represents a T lymphocyte mediated hypersensitivity reaction directed towards various antigens

Erythema Multiforme is considered rare in ____ and is most commonly associated with

dogs

drug administration and infections

rare cases of erythema multiforme is associated with

diet

some cases of EM are considered ________

idiopathic

atrophy

when cells are no longer stimulated (needed)

(Aplasia/hypoplasia: congenital defect in which the organ

was not or only insufficiently formed)

• caused decreased size of organ or tissue

Hypertrophy/Hyperplasia

when cells are over-stimulated

metaplasia

reversible; replacement of one adult cell type

(more specialized) by another cell type of the same germ

line (less specialized)

dysplasia

abnormality in maturation of cells within a tissue

(usually epithelial cells); often indicative of early neoplastic

process

hypoplasia

an organ or tissue that never reaches full size

where is hypoplasia often seen

in young animals

physiologic atrophy is also known as

known as involution

physiologic atrophy happens in

fetal development

thymus atrophy/atrophy of lymphoid tissue

senile atrophy

age-independent atrophy

why is senile atrophy called “brown atrophy”

due to intracellular “lipofuscin” accumulation

age-independent atrophy is cycle-dependent and known as

involution of uterus and mammary gland post partum

pathologic atrophy is NOT the same as

involution

what are the two types of pathologic atrophy

localized and generalized

localized pathologic atrophy includes

disuse,

neurogenic

ischemic

compression/pressure

nerve cell atrophy

types of nerve cell atrophy

retrograde, prograde, and Wallerian

what are the types of generalized pathologic atrophy

inanition and systemic

What are the two mechanisms for atrophy

1. lysosomal acid hydrolases (cathepsin)

2. ubiquitin-proteasome pathway

atrophy: cytosolic and nuclear proteins conjugated to “ubiquitin” →

degradation within a large cytoplasmic organelle: “proteasome

atrophy is often accompanied by increased numbers of

autophagic vacuoles

in atrophy: if not digestible →

membrane bound residual bodies remain (eg lipofuscin)

what is this?

rim of hyperemia in dog brain - liquefactive necrosis

what is this?

melting of tissue in spinal vertebrae with pus present - liquefactive necrosis

what is this

mammary gland from bovine with demarcated tissue and pus present - liquefactive necrosis

what is happening?

lymphoid effaced by cheese-like material - caseous necrosis

what is happening

lymph node in goat - caseous lymphadenitis, effaces normal tissue and white areas are gritty - caseous necrosis

large glomerulations of macrophages - caseous necrosis

dry gangrene on ear tips of sow

what is another common cause of dry or wet gangrene

frostbite

aspiration pneumonia - gangrenous necrosis; plant material stuck in lung

pancreatitis in dogs - fat necrosis; pancreas leaks lipase causing fat tissue necrosis - evidenced by the white tissue.

firm fat has turned into soapy mineralized material (like saponification) in cow - fat necrosis

adipocytes develop wispy blue material in fat necrosis

apoptosis of lymphocytes

apoptotic cells are shrunken causing crusting around the area

compression atrophy - cerebrum of cat that had blockage of ventricular system and causes CSF build up

horse; damage to recurrent laryngeal nerve, cricoarytenoid muscles has atrophy on one side