Disease at the Cellular Level
Cellular response to stress
2. Reversible Injury
3. Irreversible Injury, death
First changes from stress occur at...
...molecular and biochemical level.
Sequence of changes within cell from stress
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.
an immune response to host cells
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?
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
often seen in salivary gland parenchyma associated with aging
influences that induce metaplastic transformation, if persistent, may induce ______.
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 __________ ______________.
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.
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
rounded, eosinophilic inclusions formed by accumulation of newly synthesized Ig in some plasma cells
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.
deposition of calcium salts in dead or dying tissues
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.
results from energy loss for sodium pump, influx of sodium and water, "cloudy swelling"
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.
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
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)
occurs in TB, results in debri accumulation with a cheesy gross appearance
programmed cell death
a useful marker for apoptosis, however not diagnostic for programmed cell death