Disease at the Cellular Level

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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

Hypoxia

a reduction in oxygen supply to tissue

Ischemia

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

________ is the most common cause for hypoxia.

Ischemia

Immune mechanisms can react with both _________ and __________ antigens.

exogenous; endogenous

Autoimmunity

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.

Hypertrophy

an increase in the size of a cell

Hyperplasia

an increase in cell number

Atrophy

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

Aplasia

total failure of a structure to develop

hypoplasia

incomplete developement of a structure

metaplasia

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

oncocytes

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 ______.

cancer

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

heterophagy

breakdown of ingested materials

autophagy

removal of damaged or senesscent organelles

some ______ can remain undigested in lysosomes.

lipids (e.g. lipofuscin)

steatosis

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

atherosclerosis

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

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 ______.

carbon

Hemosiderin

a yellow-brown granular iron-containing pigment

hemosiderosis

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

Hemochtomatosis

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

jaundice

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

wear-and-tear or aging pigment

lipofuscin

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.

mitochondria

Severe injury of a cell will disrupt the mitochondrial ________.

membrane

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

Dilation

Membrane changes are present in...

...later stages of injury.

degenerations

light microscopic changes associated with nonlethal injury

_______ changes are rarely seen until cell death.

Nuclear

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

Necrosis

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

autolysis

when hydrolytic enzymes derive from dead cells themselves.

heterolysis

when hydrolytic enzymes derive from lysosomes of invading inflammatory cells

denaturation of protein occurs as a result of...

...a rapid drop in pH.

Karyolysis

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

pyknosis

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

Karyorrhexis

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

Pus

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

apoptosis

programmed cell death

DNA laddering

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

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