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62 Cards in this Set

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Define pathology.
The structural and fxnal causes of human disease.
What are the four aspects of a disease process that form the core of pathology?
1. etiology (cause)
2. pathogenesis - mechanism of development
3. morphological changes induced by the disease
4. clinical significance - functional consequences of the changes
What are 4 types of adaptation? Define each.
1. Atrophy - decrease in cell size

2. Hypertrophy - increase in cell size

3. Hyperplasia - increase in cell number

4. Metaplasia - change in one normal epithelial type to another normal epithelial type
What is the difference between adaptation and reversible injury?
Adaptation is caused by a stressor that changes the state of teh cell; however, it preserves the cell in the face of the exogenous stimuli.

Reversible injury - pathological changes that occur to the cell but cell can be returned to normalcy is the stimuli is removed.
What are two patterns of cell death? Which one is always associated with a pathological process?
Necrosis and apoptosis

Necrosis = always pathological
What are 7 causes of cell injury?
1. oxygen deprivation: ischemia, loss of oxygen carrying capacity, inadequate oxygenation

2. physical damage
3. chemical damage
4. infectious agents-viruses, bacteria, fungi, parasites
5. immunologic reactions - autoimmune dz and rxn to infection
6. genetic derangements
7. nutritional imbalances
Cell injury results from abnormalities in one or more of 5 essential cellular components... Name the 5 components.
1. Aerobic respiration - ox phos and ATP production
2. Maintenance of cell membrane integrity
3. Protein synthesis
4. Intracellular cytoskeleton
5. Integrity of the genetic apparatus
What are some causes of mitochondrial damage?
hypoxia, toxins, increased cytosolic Ca(2+), oxidative stress, phospholipid breakdown
What are consequences of mitochondrial damage?
Formation of mitochondrial permeability transition (MPT)

-- this causes the leakage of portons and disspiates the electron motive potential that drives ox phos

Can also leak cytochrome c, triggering apoptosis - cyt c will bind with Apaf-1
What 2 phenomena consistently characterize irreversibility of cell injury?
1. inability to reverse mitochondrial dysfunction even after resolution of the original injury

2. Development of profound disturbances in membrane function
What are the 2 characteristics of reversible cell injury?
1. cell swelling - cant maintain ionic and fluid homeostasis

2. fatty change - lipid vacuoles found in cells involved in or dependent on fat metabolism
What are the 2 processes that underlie the basic morphologic changes in necrosis?
1. Denaturation of proteins

2. Enzymatic digestion of organelles and other cytosolic components
What are distinctive features of necrotic cells?
1. eosinophilic
2. calcium deposits - complex with phosphates to form soaps
3. pyknosis
4. karyorrhexis
5. karyolysis
Describe reperfusion injury.
Restoration of blood flow after irreversible injury can exacerbate the injury.

1. Reperfusion can cause the additional formation of free radicals from epithelial and parenchymal cells
2. Formation of free radical since the mitochondria is not completely reducing oxygen
3. Increased inflammation due to increased neutrophils entering site and producing more cytokines
4. When blood flow resumed, have activation of complement system -- complement proteins bind to Abs, are activated, and cause inflammation
5. ROS can promote MPT
What are the morphologic features of apoptosis?
cell shrinkage, chromatin condensation and fragmentation, cellular blebbing and fragmentation into apoptotic bodies, and pagocytosis of apoptotic bodies by adjacent healthy cells or macrophages

lack of inflammation
What are the 2 phases that apoptosis are divided into? The first phase also has sub-divisions - name them.
Initiation and Execution Phase

Initiation phase is divided into:
1. extrinsic phase (receptor mediated)
2. intrinsic phase (mitochondrial pathway)
Describe the extrinsic pathway of the initiation phase of apoptosis.
Death receptors are part of the TNF-alpha receptor family. They consist of a death domain that when ligands bind to each domain they cross link each other. This causes the formation of binding sites for adaptor proteins. This causes inactive caspase-8 activity into close proximity. The low level enzymatic activity casuses a caspase cascaded to occur.
Which caspase is associated with the extrinsic pathway of the initiation phase of apoptosis?
Caspase 8
Which caspase is associated with the intrinsic pathway of the initiation phase of apoptosis?
Caspase 9
Describe the intrinsic pathway in the initiation phase of apoptosis.
Mitochondrial permeability is increased and pro-apoptotic molecules are released into the cytoplasm. Death receptors are not involved!

Bcl-2 and Bcl-x are anti-apoptotic proteins. When cells are subject to stress or lose survival signals, these two proteins are replaced with Bax, Bim, and Bak.

Mitochondrial permeability is increased, leaking out proteins.

Cyt c leaks out and binds with Apaf-1 and caspase 9 is activated.
What is the importance of the term "caspase."
C = cysteine in active site

aspase = aspartic acid - can cleave after aspartic acid residues
Which caspases are initiator caspases?
8 and 9
Which caspases are executioner caspases?
3 and 6
What does caspase-3 activate?
activates a cytoplasmic DNAase resulting in characteristic internucleosomal cleavage of DNA -- cutting DNA into ladders of 200 bps
Fas-FasL interactions are important for eliminating?
lymphocytes that recognize self antigens
What secretes perforin?
Cytotoxic T cells
What is perforin?
transmembrane pore forming molecule that allows entry of the cytotoxic derived serine protease granzyme B
What is granzyme B?
enzyme that enters a cell and cleaves proteins after aspartate residues and thus, activates multiple caspases
What is the difference between heterophagy and autophagy?
Heterophagy involves uptakes and degradation of materials from the EXTERNAL environment by phagocytosis.

Autophagy involves the lysosomal degradation of degenerating INTRACELLULAR organelles.
What are residual bodies?
undigested debris or abnormal substances that cannot be completely be metabolized may persist within cells as residual bodies.
What are lipofucin pigment granules?
undigested material derived from intracellular lipid peroxidation
What is megamitochondria and when is it usually seen?
Abnormally large mitochondria

Seen in hepatocytes in alcoholic liver disease or nutritional disease
What are oncocytomas?
Benign tumors consisting of cells with abundant enlarged mitochondria.
What is fstt steatosis?
occurs when a normal constituent (triglycerides) accumulates, leading to an absolute increase in intracellular lipids
What is anoxia?
Decreased fatty acid oxidation
What is cholesterolosis?
Focal accumulations of cholesterol-laden macrophages occur in the lamina propria of gallbladders.
What is Niemann Pick Disease, type C?
lysosomal storage disease due to mutation of an enzyme involved in cholesterol metabolism
Describe alpha-1 antitrypsin disease
mutations slow protein folding

partially folded intermediates accumulate in the ER of hepatocytes

loss of antitrypsin leads to emphysema
Describe the relationship of misfolded proteins and CF.
Most common mutation delays dissociation of the chloride channel protein from its chaperones, resulting in abnormal folding and subsequent degradation.
What is anthracosis?
exogenous pigments deposit and accumulate in pulmonary macrophages and lymph nodes.
What is hemosiderin?
hemoglobin derived, golden yellow brown granular intracellular pigment composed of aggregated ferritin.
What is the difference between dystrophic and metastatic calcification?
Dystrophic calcification occurs to nonviable or dying tissues in the presense of normal calcium levels.

Metastatic calcification occurs in normal tissues and is associated with hypercalcemia.
What are the two steps of dystrophic calcification and describe them?
1. Initiation -- can be intracellular or extracellular
2. Propagation

Extracellular occurs on membrane bound vesicles from dead or dying cells that concentrate calcium due to their content of charged phospholipids; membrane bound phosphotases generate phosphate that form calcium phosphate complexes

Intracellular - calcification occurs in mitochondria of dead or dying cells.

Propagation of crystal formation depends on concentration of calcium and phosphates
What are the 4 principle causes of metastatic calcificaiton?
Occurs due to hypercalcemia

1. increased secretion of parathyroid hormone
2. destruction of bone tissues
3. Vit D related disorders
4. Associated with renal failure
What is the Hayflick theory?
Cells have finite life spans in culture.... they have clocks...

in reference to cellular senescence - cells have limited capacity for replication
What is Werner Syndrome?
premature aging caused by a defect in DNA helicase, resulting in rapid accumulation of chromosomal damage.
Describe calcium homeostasis.
Cytosolic calcium is maintained at extremely low levels. Cell injury causes calcium influx across the plasma membrane and release of calcium from mitochondria and ER.

Increase cytosolic Ca activates phospholipases, proteases, ATPases, endonucleases
Name storage and transport proteins that help minimize reactive oxidative species by binding to them.
transferrin, ferritin, lactoferrin, and ceruloplasmin
Name some enzymes the scavenge and catabolize hydrogen peroxide and superoxide anion.
catalase, glutathione, peroxidase, superoxide dismutase
What is the first manifestation of almost all forms of injury to cells?
Cellular swelling
The pattern of cellular swelling is also sometimes called....?
hydropic change or vacuolar degeneration
The ultrastructural changes of reversible cell injury include:
plasma membrane alterations
mitochondrial changes
dilation of the ER
nuclear alterations
What type of necorsis is dominated by protein denaturation?
Coagulative necrosis
What type of necrosis implies the preservation of the basic outline of the coagulated cell? Why does this happen?
Coagulative

Occurs because the intracellular acidosis denatures not only structural proteins byt also enzymes and so blocks the proteolysis of the cell.
Liquefactive necrosis is characteristic of...?
focal bacterial or occassional fungal infections because microbes stimulate the accumulation of inflammatory cells
Caseous necrosis is most often seen in what type of infections? Describe the appearance of this type of necrosis.
tuberculous infections

cheesy white appearance with amorphous granular debris
granulomatous reaction
Chemical injury can occur by 2 mechanisms. What are they and give examples of each?
Directly binding to some critical molecular component - mercuric chloride binds to cell membrane protein, inhibiting ATPas-dependent transport and causing increased permeability.

Indirectly - by conversion to reactive toxic metabolites
Carbon tetrachloride - its conversion by P450 to the free radical CCl(3)

Acetominophen - detoxed in liver and small amounts are converted by cyt P450 oxidation. The intermediate is detoxed with GSH. When large amounts are consumed, GSH is depleted and the toxic metabolites accumulate.
Steatosis is commonly seen in which two organs? Which organ is often seen with a tigered appearance?
Liver and Heart

Heart -- due to accumulation of fat that gives an alternating banding appearance
Abnormal intracellular accumulations of intermediate filaments are called?
Mallory bodies
What are Russell bodies?
Ig distending the ER of plasma cells due to much synthesis... accumulate and form Russell bodies
What are three interrelated processes that likely accounty for cellular aging?
1. replicative senescence
2. genes that influence the aging process
3. progressive accumulation of metabolic and genetic damage due to continuous exogenous influences
With pathological calcification, psamooma bodies can be formed. What are psamoma bodies?
progressive acquisition of outer layers of calcium that create lamellated configurations of calcium deposits