Term
| for this course pathology is what? |
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Definition
| the study of the nature and cause of disease which involves changes in structure and function |
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Term
| disease results from what 3 primary abnormalities |
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Definition
genetic function
physiological/biochemical function
gross structural arrangement of cells, tissues, organs |
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Term
| what is a disease process or response |
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Definition
| a consistent pattern of pathiologic change characteristic of an underlying mechanism |
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Term
| what are the basic pathological proccesses/responses |
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Definition
adaptations of cells to changes in their environment
what happens to cells when they cannot adapt, and how cells die
disorders of cell growth (cancer)
tissue responses to injury (inflammation) and how tissues heal/repair
genetic and immune factors in disease
adverse environmental factors that cause disease
circulatory disturbances |
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Term
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Definition
the cause(s)or origin of disease or disorder
1) many disease have 1 cause
2)individuals react differently to same etiologic agent
3)some disease have many cuases (risk factors) |
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Term
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Definition
| the pathways and mechanisms of a disease process |
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Term
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Definition
| the objective physical alterations of disease observed in patient's body and recorded by health professional |
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Term
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Definition
| subjective feelings and complaints that the patients expresses |
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Term
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Definition
| any pathological or traumatic disontinuity of tissue or loss of function of a part. the concept has been broadened to include molecular level |
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Term
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Definition
| secondary effects of primary process |
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Term
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Definition
recognition of a specific disease
a)differential diagnosis- possible diagnosis in order or probability on the known findings
b)it is not always possible to reach a diagnosis
c)its an art- knowledge curiosity, care observation, guess work, persistance
d)diagnosis leads to rational, timely tx
b) |
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Term
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Definition
forecast of probable outcome of a disease, the prospect as to recovery from a disease as indicated by nature and symptoms of a case
1) its what the patient wants to know
2)not always clear
3) sometimes tx or cure is worse than disease |
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Term
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Definition
the study of the relationships of various factors determinig the frequency and distribution of a disease and thereby contribute to a prevention
b)such studies can also track down the source of a disease |
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Term
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Definition
the science of disease classification
a)many possible classification systems
b)most common system is based on the basic disease process such as the classification previously listed |
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Term
| functional states of a cell |
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Definition
normal, steady state
adapted state
reversibly damanged state
irreversibly damaged state
cell death |
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Term
| cells as adaptable units- what stresses do they undergo? |
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Definition
normal physiologic processes(intrinsic)
external environment changes- extrinsic |
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Term
features of physiologic metabolic adaptations (biochemical fine tuning- happens all the time)
3 examples |
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Definition
-no visibly detectable changes in cell structure
fastine = mobilization of fatty acids for energy
decrease in serum calcium causes increase in parathyroid hormone- increase activity or osteoclasts
drugs- hepatic microsomal enzymes induced to facilitate drug metabolism |
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Term
| physiologic structural adaptations- 3 examples |
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Definition
change in the normal pattern of growth of cells resulting in adaptive structural changes
1)increased cellular activity (increased size or number of cells) often increased functional demands or hormonal stimulation
2)decreased cellular activity (reduced size or number of cells) often reduced functional demands or hormonal stimulation
alteration of cell morphology- alteration of cellular differentiation |
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Term
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Definition
| severe changes in the cellular environment that are the result of a disease |
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Term
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Definition
series of metabolic changes in cells which are important basic mechanisms enabling cellular survival during environmental insults and minimize injury
-genes coding for normal structural proteins are down regulated (house keeping genes)
-genes coding for proteins which have cell organizing and protective functions (cell stress genes) are upregulated |
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Term
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Definition
-expressed at low levels until exposure of cell to potentially injurious stimuli (heat, hypoxia, heavy metals, radiation, viral infection),
rapid response that minimizes cell damage and represents an adaptive response to ensure cell viability
Hsp 70 family may play a role in refolding of denatured polypeptides
-ex- chaperonins which plays a role in protein kinesis- protein folding, disaggregation, intracellular transport, denaturation)
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-highly conserved
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Term
| adaptive response in disease |
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Definition
| cells may also adapt to injurious stimuli by undergoing a modification fo a new, different steady state of metabolism and structure that better positions the cells/tissues to surivive in an abnormal environment or disease state - extensions of the physiologic structural adaptations (increase, decreased cell activity, and alteration of cell morphology) |
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Term
| failure to adapt in disease states may result in what? why does this happen |
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Definition
cell injury or death
1)cell type- some more susceptible than others
2)environmental changes are so severe that stress and adaptive responses are quickly overwhelmed |
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Term
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Definition
increases in number of cells in organ or tissue
due to increased functional demand
chronic cell injury
hormonal stimulation- physiologic and pathologic |
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Term
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Definition
increase in size of a cell accompanied by increased functional capacity
increased functional demand (muscle tissue)
uncommonly- physiologic hormonal hypertrophy, response to abnormally high hormone levels) |
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Term
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Definition
| decrease in number of cells in tissue or organ |
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Term
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Definition
decrease in size and function of cell or organ
reduced functional demand
hypoxia or decrased blood supply to cells- ischemia
insufficient nutritional supply
persistent (chronic) cell injury
aging |
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Term
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Definition
| change in pattern of cellular differentiation from one mature stable cell to another mature, stable cell which is better able to withstand the environmental stress |
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Term
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Definition
| failure of formation of embryonic organ anlage resulting in complete absence of an organ or specific portion of an organ |
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Term
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Definition
| organ primordium is present but failed to differentiate into a developed organ |
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Term
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Definition
| incomplete development of an organ resulting in reduced size |
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Term
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Definition
| organ specific structures develop but lack correct histoanatomical(structural) organization |
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Term
| metaplasia- change in cell differentiation |
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Definition
transformation of one differentiated cell type to another differentiated cell type
reversible, functional adaptation to altered environment
most common is replacement of glandular epithelium with squamous epithelium |
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Term
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Definition
divide often and constantly thru life
particularly susceptible to injury |
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Term
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Definition
| divide infrequently- can respond to external stimuli by increasing rate of mitosis for regeneration or repair |
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Term
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Definition
do not divide in adult life
no capacity to replace injured or dead cells with new cells |
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Term
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Definition
| state of balance between opposing pressures operating in and around cells and tissues |
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Term
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Definition
| when environmental alterations exceed the capacity of the cell to maintain normal homeostasis |
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Term
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Definition
| adverse environmental stimuli/insults are typically mild and short lived |
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Term
| potentail injurious stimuli/agents |
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Definition
hypoxia-reduced availability of oxygen to cells
chemical (drugs, toxins, poisons, caustic agents)
physical- excessive heat or cold, mechanical injury, radiation
infection
inflammation and immune reactions
genetic and metabolic disorders |
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Term
| mechanisms of cell injury |
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Definition
blockage of specific metabolic pathways
deprivation of essential metabolites -o2 and glucose
generation of free radicals
impaired cell membrane integrity
direct damage to DNA
mechanical trauma disrupting cell membranes (oftn irreversible) |
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Term
| morphologic patterns of reversible cell injury |
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Definition
hydropic change
fatty change |
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Term
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Definition
cloudy swelling, hydropic swelling, vacuolar degeneration
increased water within cytoplasm of the cell
impaired fluid volume regulation by the injured cell
pm permeability to sodium
damage to plasma membrane sodium pump
impared synthesis of ATP pump fuel |
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Term
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Definition
abnormal accumulation of lipids w/in cytoplasm
impared lipoproten synthesis
excessive lipid formation
inhibition of lipid degradative enyzmes |
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Term
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Definition
| when stresses to which a cell must react it too severe or prolonged the cellular changes which result lead to the death of a cell |
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Term
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Definition
consequence of catastrophic injury to the mechanisms responsible for maintaining integrity of a cell
characterized by: breakdown of homeostatic control
cell swelling and mitochondiral damage leading to rapid of energy levels ATP
cell membrane lysis and release fo intracellular contnets- leading to an inflammatory response with edema and damage to the surrounding cells |
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Term
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Definition
| energy dependent- genetically determined cell death program initiated under a variety of physiologic and pathologic circumstances |
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Term
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Definition
| the nature of the injurious stimulus and the type of tissue affected will determine morphologic patterns of necrosis |
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Term
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Definition
| condensation of chromatin in necrosis |
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Term
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Definition
| fragmentation of nucleus into smaller particles |
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Term
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Definition
| lysis of chromatin by enzymes |
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Term
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Definition
most frequently encountered type of necrosis
often caused by decreased o2 supply to cell and tissues involved
rapid inactivation of cytoplasmic hydrolytic enzymes
cytoplasmic proteins coagulate- cells retain general form affected tissues initially remain relatively firm |
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Term
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Definition
tends to occur when enzymatic digestion of tissues predominates
necrosis of brain
localized acute inflammation (abscess) |
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Term
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Definition
unique form of necrosis with coagulative changes and limited degree of liquefaction
prototypical disease is TB
necrotic tissue has a cheese-like consistency |
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Term
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Definition
| usually results from traumatic injury to adipose tissue or release of lipases from injured pancreatic acinar cells |
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Term
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Definition
| necrotic tissue that becomes secondarily infected by bacteria - extremities, bowels |
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Term
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Definition
unqiue form of necrosis resulting in amorphous proteinaceous material
prototypical disease is syphilis
necrotic tissue has a firm, rubbery consistency |
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Term
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Definition
dead tissue is permeated with extensive amts of erythrocytes
often associated with blockage of venous drainage of a tissue, congestion and subsequent failure of arterial perfusion |
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Term
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Definition
| necrosis of vessels- usually arteries in disease associated with primary inflammation of b.v. walls- extensive fibrin deposition in necrotic vessel wall |
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Term
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Definition
| a biologic process involving interactions between genetically determined and environmentally influenced events |
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Term
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Definition
| intrinsic genetic mechanism determines life span of cells |
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Term
| replication senescence theory |
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Definition
accumulation of variety of injuries to cell and tissues
DNA repair defects
degeneration in extracellular matrix components
free radical damage
inefficient elimination of damaged cell elements
(wear and tear) is responsible for cellular aging and ultimately cellular and organism failure |
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Term
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Definition
| energy dependent pathway of cell death induced by tightly regulated intracellular program |
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Term
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Definition
cell destined to die activate enzymes that degrade the cell's own nuclear DNA and nuclear and cytoplasmic proteins
plasma membranes remain intact, but stucture is altered such that apoptotic cells become avid targets for phagocytosis
dead cells are rapidly cleared b4 contents leaked out- avoids acute inflammatory response |
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Term
| physiologic situations of apoptosis |
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Definition
embryogenesis and developmental involution
hormone dependent involution
cell deletion in tissues of high cellular turnover
clonal selection of lymphocytes during self tolerance development eliminates potentially auto reactive lymphocytes |
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Term
| pathologic conditions of apoptosis |
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Definition
-cell death induced by variety of stimuli- DNA damage
cytotoxic T lymphocyte mediated cell death
inflammatory and immune cell elmination after function completed-
deprivation of growth factors required for survival
virally infected cells
elimination of neoplastic cells in tumors |
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Term
| 3 main phases of pathogenetic mechanism of apoptosis |
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Definition
induction/signalling/initiation
degradation/execution
phagocytosis dead cell removal |
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Term
| induction/signalling/initiation |
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Definition
-extrinsic (death receptor initiated) pathway
-intrinsic (mitochondria) pathway
-DNA damage mediated pathway |
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Term
| extrinsic death receptor initiated pathway |
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Definition
receptor ligan interactions trigger signal transduction cascade
death receptors- TNF, FAS
binding of ligand binds three or more receptors allowing binding of various adaptor proteins
adaptor proteins bind multiple pro caspase molecules molecules which catalyzes conversion to active initiator caspases (caspase 8) |
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Term
| intrinsic mitochondrial pathway |
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Definition
deprivation of growth/survival signal or cell damage (radiation toxins free radicals, anoxia, increased free Ca++) results in loss of anti apoptotic proteins- Bcl2 and Bclx
increased permeability of mitochondrial membrane MPT permeability transition pore complex PTPC
cytochrome C and other pro-apoptotic proteins released into cytosol
binding to Apaf-1 complexes bind pro caspases molecules which catalyzes conversion to active initiator caspases- caspase 9 |
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Term
| DNA damage mediated pathway |
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Definition
genotoxic stress/damage to DNa- radiation- drugs
accumulation of p53 for cell cycle arrest and DNA repair
failure of DNa repair results in p53 triggering apoptosis
mechanisms not entirely clears
stimulation production of pro apoptotic protein of Bcl2 family called Bax and Bak
induction of genes that code death receptor transmembrane proteins Fas
direct activation of caspase 6 |
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Term
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Definition
converstion of inactive, caspase pro enzymes (3,6) into active proteases
active caspases mediate a wide variety of biochemical and structural alterations within cells
cleave cytoskeletal and nuclear matrix proteins
target proteins involved in DNA replication DNa repair and transcription
activate DNAases which degrade nuclear DNA in 180 and 200 bp |
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Term
| phagocytosis and dead cell removal |
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Definition
apoptotic cells secret soluble factors which recruit phagocytes
phosphatidylserine expression on outer surface of plasma membrane
early recognition of apoptotic cells resulting in phagocytosis wihtout release of proinflammatory cellualr components |
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Term
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Definition
damage to supporting stromal cells is limited following injury and inflammatory reaction
inflammaotry exudate and fragemented tissue debris removed by enzymatic liquefaction and phagocytosis
regeneration of cells to replace damaged and dead cells
labile and stable populations
normal structure and fucntion is acheived |
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Term
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Definition
fibroproliferative response that patches rather than restores a tissue
complex but orderly phenomenon
induction of an inflammatory process in response to the initial injury with removal of damaged and dead tissue
proliferation and migration of parenchymal and connective tissue cells
formation of new blood vessels (angiogenesis) and granulation tissue
synthesis of ECM proteins and collagen deposition
tissue remodeling
wound contraction
acquisition of wound strength |
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Term
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Definition
| replacement of inflammatory exudate and damaged tissue elements by granulation tissue |
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Term
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Definition
term derives from its pink,soft, granular appearance on the surface of wounds
formation of new small blood vessels angiogenesis and the proliferation of fibroblasts |
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Term
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Definition
for preexisting vessels- capillary sprouting
mobilization of endothelial precursor cells from bone marrow |
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Term
| growth factors and receptors of angiogenesis |
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Definition
| VEGF family FGF 2 angiopoietins (stabilization) |
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Term
| extracellular matrix proteins of angiogenesis |
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Definition
facilitate motility and directed migration of endothelial cells
integrins matricellular proteins, mmps |
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Term
| growth factors and cytokines of granulation tissue |
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Definition
grwoth factors- PDGF, EGF, FGF< TGF BETA
cytokines- TNF, il-1 |
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Term
| granulation tissue replaced by fibrous scar characterized by: |
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Definition
dense collagen
fragments of elastic tissue
extracellular matrix components
reduced numbers of fibroblasts as process proceeds
vascular regression (apoptotic mechanisms) |
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Term
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Definition
replacement of granulation tissue with a scar involves transitions int he composition of the ECM
balance between ECM synthesis and degradation results in remodeling of the connective tissue framework- an important feature of wound repair
degradation of collagen and other ECM proteins is done by MMPS |
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