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Cellular response to stress

1. Adaptation
2. Reversible Injury
3. Irreversible Injury, death

First changes from stress occur at...

...molecular and biochemical level.

Sequence of changes within cell from stress

1. Biochemical
2. Functional
3. Morphologic


a reduction in oxygen supply to tissue


a loss of blood supply to tissue due to impeded arterial flow or reduced venous drainage.

________ is the most common cause for hypoxia.


Immune mechanisms can react with both _________ and __________ antigens.

exogenous; endogenous


an immune response to host cells

Hemoglobin S

The affected protein in sickle cell anemia. exhibits a single amino acid substitution.

Aging can result in...

...a diminished ability to respond to exogenous stimuli and injury.


an increase in the size of a cell


an increase in cell number


a decrease in the size of a cell

causes of atrophy

decreased workload, a loss of innervation, a diminished blood supply, inadequate nutrition, a loss of endocrine stimulation, and aging.

What forms in atrophy in order to catabolize self-components?

Autophagic vacuoles

membrane-bound residual bodies

vacuoles which contain materials that resist digestion and persist in the cytosol


total failure of a structure to develop


incomplete developement of a structure


a change in which one adult cell type is replaced by another adult cell type


large epithelial cells that contain a brightly eosinophilic, granular cytoplasm packed with mitochondria

oncocytic metaplasia

often seen in salivary gland parenchyma associated with aging

influences that induce metaplastic transformation, if persistent, may induce ______.


Barrett esophagus

the transformation in chronic gastric reflus of esophageal stratified squamous epithelium to gastric or intestine-type columnar epithelium.

Barrett esophageal metaplasia has been linked to __________ ______________.

esophageal adenocarcinoma

Heat Shock Proteins

function as stress proteins after injury to refold and restore function of denatured proteins. also tag irreversibly denatured proteins for disposal.

Use of barbituates leads to...

...induction of hepatocyte SER and metabolic (P-450 mixed function oxidase system) enzymes.

results of cytoskeletal abnormalities

aberrant movement of intracellular organelles, defective cell locomotion, or intracellular accumulations of fibrillar material.

Primary lysosomes

membrane-bound intracellular organelles containing a variety of hydrolytic enzymes


breakdown of ingested materials


removal of damaged or senesscent organelles

some ______ can remain undigested in lysosomes.

lipids (e.g. lipofuscin)


fatty change, most often seen in liver rusulting from alcohol abuse


when smooth muscle cells and macrophages are filled with lipid vacuoles composes of cholesterol and cholesteryl esters

Russell bodies

rounded, eosinophilic inclusions formed by accumulation of newly synthesized Ig in some plasma cells

Mallory body

an eosinophilic intracytoplasmic inclusion of aggregated prekeratin intermediate filaments in liver (characteristic of alcoholic disease)

In poorly controlled diabetes mellitus, ________ is seen within the kidney, heart, and pancreas.


Glycogen storage disease

enzymatic defects in the synthesis or breakdown of glycogen resulting in massive stockpilin, with secondary injury and cell death.

the most common exogenous pigment inclusions are ______.



a yellow-brown granular iron-containing pigment


a systemic excess of iron, which does not cause tissue damage


a systemic iron overload disorder, which causes parenchymal tissue damage.


a buildup of bilirubin, usually seen in skin and eyes from obstruction of bile duct

wear-and-tear or aging pigment


Presence of lipofuscin is an important marker of...

...past free radical injury

Melanin is synthesized from ________ via __________ in ___________.

tyrosine; tyrosinase; melanocytes

_____ _____________ adjacent to melanocytes may accumulate melanin.

Basal keratinocytes

Dystrophic calcification

deposition of calcium salts in dead or dying tissues

Metastatic calcification

reflective of hypercalcemia, deposition of calcium salts in normal tissues

Sites of cell injury

1. cell membrane integrity
2. ATP generation
3. protein synthesis
4. integrity of genetic apparatus

Mild cellular injury may cause swelling of the ____________ with disappearance of granules.


Severe injury of a cell will disrupt the mitochondrial ________.


________ of the ER is one of the first ultrastructural manifestations of increased cell permeability.


Membrane changes are present in...

...later stages of injury.


light microscopic changes associated with nonlethal injury

_______ changes are rarely seen until cell death.


Cellular swelling

results from energy loss for sodium pump, influx of sodium and water, "cloudy swelling"

hydropic degeneration

severe cellular swelling producing clear vacuoles in cyoplasm, aka vacuolar degeneration.

Fatty changes are a sign of...

...more severe cellular injury.

The presence of what enzymes are diagnostic for MI?

glutamic-oxalacetic transaminase, lactic dehydrogenase, and creatine phosphokinase


the sequence of morpholigic changes that follow cell death in living tissue


when hydrolytic enzymes derive from dead cells themselves.


when hydrolytic enzymes derive from lysosomes of invading inflammatory cells

denaturation of protein occurs as a result of...

...a rapid drop in pH.


a progressive fading of the basophilia a chromatin, due to DNase


shrinking of the nuclear chromatin, due to destruction and condensation of nuclear material


fragmentation of pyknotic chromatin

hallmark appearance of dead cell

cell with an eosinophilic granular outline, devoid of a nucleus or any internal cytoplasmic structures.

Liquifaction Necrosis

results in an abscess filled with pus, characteristic of bacterial infections and hypoxic damage of CNS


fluid composed of digested cellular debris, neutrophils, and fluids

Coagulation Necrosis

rapid denaturation of all cellular proteins, including lysosomal enzymes, resulting in blockage of cellular digestion

cuagulation necrosis is characteristic of...

...hypoxic death in all tissues other than CNS. (MI)

Caseous Necrosis

occurs in TB, results in debri accumulation with a cheesy gross appearance


programmed cell death

DNA laddering

a useful marker for apoptosis, however not diagnostic for programmed cell death

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