Adaptation, Injury, and Death + Cell Injury (SS 01) Flashcards
define necrosis
death of cells, tissues, or organs in a living person
define apoptosis
programmed cell death of single cells
define ischemia
reversible injury due to inadequate blood supply
define infarction
irreversible necrosis due to ischemia that is not relieved in time
is the same treatment used for all types of necrosis?
no, type of necrosis determines treatment
what type of treatment is used in the case of liquefactive necrosis?
drainage
what type of treatment is used in the case of caseous necrosis?
anti-fungal and TB
what type of treatment is used in the case of gangrenous necrosis?
amputation
pathologic apoptosis is important in ___
certain cancers (lack of it), chemo, radiation, transplant rejection, hypoxia, certain viral infections
define etiology
cause
define morphology
visible manifestation
define gross
visible without a microscope
what is the gradation of response to stress and noxious stimuli?
adaptation –> injury –> death
define adaptation
physiologic and morphologic changes, modulating function, bringing it to a new altered steady state of homeostasis
when it comes to adaptive ability, most vital organs have a large ___
reserve capacity
what is the relationship bw disease and reserve capacity?
disease commonly uses up an organ’s reserve capacity silently until it’s too late
define injury
reversible pathophysiologic and morphologic response to stress or noxious stimuli exceeding the capacity of cell, tissue, organ or person to adapt, though not enough to be lethal
what are the injurious reactive oxygen species (ROS)?
superoxide, hydrogen peroxide, hydroxyl radical, and peroxynitrite
what is reperfusion?
restoration of blood supply to ischemic cells
what can reperfusion lead to?
can be injurious bc brings oxygen that can be converted to ROS and calcium that can increase mitochondrial permeability and activate enzymes inappropriately in cells already damaged
injured and dead cells leak their contents into the bloodstream which are useful how?
blood tests can detect these contents to diagnose tissue injury or necrosis
what is amylase?
enzyme that digests carbs
what is amylase secreted by?
pancreas (into duodenum) and salivary glands (into saliva)
what is lipase?
enzyme that digests fats
what is lipase secreted by?
pancreas (into duodenum)
in a case of pancreatitis where is lipase released?
retroperitoneal peri-pancreatic fat (leading to fat necrosis)
what is creatine phosphokinase (CPK or CK)?
enzyme concentrated in muscle and brain composed of M and B dimers
what is CK secreted by?
myocytes –> MB fraction is secreted into blood with myocardial injury
what is ALT?
alanine aminotransferase, transaminase that catalyzes interconversion of glutamate and alanine
what is ALT secreted by?
liver normally releases it, but more is secreted by liver injury than AST
what is AST?
aspartate aminotransferase, transaminase that catalyzes interconversion of glutamate and aspartate
what is AST secreted by?
muscle, liver, and other organ injury
what is ALP?
alkaline phosphatase, phosphatases that transfer phosphate from donor to receptor molecules at alkaline pH
what is ALP secreted by?
liver and bone injury, esp. with biliary obstruction and space-occupying disease
what is GGT?
gamma-glutamyl-transferase, outer cell membrane enzyme that transports amino acids into cells
what is GGT secreted by?
liver injury (esp. toxic)
what is LDH?
lactate dehydrogenase, enzyme that catalyzes conversion of lactate to pyruvate by removing 2H
what is LDH secreted by?
injury to RBCs, liver, muscle, other organs
what is coagulative necrosis?
morphological manifestation of irreversible injury to cell, tissue, organ due to ischemia (except in brain)
is ischemia reversible or irreversible?
reversible
is infarction reversible or irreversible?
irreversible
what is pyknosis?
condensation, shrinkage , and hyperbasophilia (increased blue) of a dead cell nucleus
what is karyorrhexis?
clumping and fragmentation of nuclear DNA in a pyknotic dead nucleus
what is karyolysis?
fading away of a dead cell nucleus
what are the features of coagulative necrosis?
1) preservation of ghost outline
2) cytoplasm has increased pink eosinophilia
3) nucleus exhibits pyknosis, karryorhexis, karyolysis
4) acute inflammatory response
what is liquefactive necrosis?
necrosis with conversion of solid tissue to liquid due to severe acute infection, toxicity, or (brain only) ischemia
what is an abscess?
localized area of liquefactive necrosis
what is a microabscess?
localized area of liquefactive necrosis visible only microscopically
what is caseous necrosis?
distinctive form of coagulative necrosis grossly resembling cheese
what are the features of caseous necrosis?
amorphous, granular, eosinophilic, no ghost cells
what is gangrene necrosis?
distinctive form of coagulative necrosis with blackening and shrinkage , typically of distal extremities, but sometimes of internal organs such as gallbladder
what is fat necrosis?
adipose tissue digested by pancreatic lipase, creating white saponification (most common form) –> can result from trauma
what does saponification of fat entail?
chalky white deposits of calcium + fatty acid soap from digestion by pancreatic lipase
what 2 pathways can initiate apoptosis?
mitochondrial (internal/intrinsic) and death receptor (external/extrinsic)
can protein misfolding lead to pathologic apoptosis?
yes
what are the features of apoptosis?
1) cell shrinkage
2) cytoplasmic hypereosinophilia
3) chromatin condensation and karyorrhexis
4) phagocytosis by macrophages
do apoptosis and necrosis occur within 1) single cells/small clusters or 2) large groups of cells?
apoptosis = single cells/small clusters necrosis = large groups of cells
do apoptosis and necrosis occur with 1) cell membrane intact or 2) cell membrane disrupted?
apoptosis = intact necrosis = disrupted
do apoptosis and necrosis produce an inflammatory response?
apoptosis = no necrosis = yes
physiologic apoptosis is important in ___
embryogenesis, involution, ending inflammation, eliminating self-reactive lymphocytes, eliminating virally infected and tumor cells, etc.
define lesion
discrete visible manifestation of disease
define physiology
normal function
define pathophysiology
abnormal function, rendered abnormal by disease
define pathogenesis
sequence of events in response of person, organ, or cell to etiologic agent of disease (from initial stimulus to ultimate manifestation of disease)
what is Occam’s razor as it applies to medicine?
a single diagnosis that explains all of a patient’s symptoms, signs and other manifestations of disease is most likely the correct diagnosis
the electrolyte potassium is most important to what?
muscle
the electrolyte sodium is most important to what?
brain (and nerves)
the electrolyte bicarbonate is most important to what?
acid-base balance
which part of the small intestine is most difficult to diagnose injury to?
jejunum
liver injury is more likely than any other organ to elevate ___ out of proportion to ___
ALT; AST
what four factors have influence on whether reversible ischemia becomes irreversible infarction?
1) vulnerability of the disease
2) rate of development
3) alternative blood supply
4) blood oxygenation
infarctions tend to be ___, ___, and ___-shaped
peripheral, subcapsular, and wedge-shaped
white anemia infarcts are typical of ___
solid organs with end-arterial circulation (e.g., heart, spleen, kidneys)
red hemorrhagic infarcts have what different mechanisms?
venous occlusion, dual or anastomosing blood supply or reperfusion
the brain tends to develop what type of necrosis?
liquefactive
do all cell types react to stress and injury the same way?
no
define atrophy
decrease in size and function of cell or organ due to disuse, aging (senile atrophy), denervation, decreased blood supply, etc.
define hypertrophy
increase in size of a cell caused by augmented functional demand or specific hormonal stimulation; can be physiologic or pathologic
define hyperplasia
increase in number of cells in an organ or tissue; can be physiologic or pathologic
define polyploidy
the state of a cell nucleus containing 3+ haploid chromosomal sets
define metaplasia
conversion of one differentiated cell type to another differentiated cell type; can be epithelial or mesenchymal
define dysplasia
alteration of size, shape, and organization of cellular components of a tissue
what is the difference bw hypertrophy and hyperplasia?
hypertrophy = larger cells hyperplasia = more cells (but same size)
is polyploidy always indicative of unrestricted cell growth?
no
metaplasia is based on what concept?
entire genetic code is contained within every cell
metaplasia typically begins where (within epithelium)?
at base of epithelial surface along basement membrane, first in reserve cells then the rest of the cells
what is dysplasia characterized by?
1) abnormalities in size and shape of cells
2) enlargement, irregularity, and hyperchromasia of nuclei
3) disorderly arrangement of cells within epithelium
4) generally preneoplastic condition
name the common intracellular, endogenous brown pigments
iron compds, lipofuscin, melanin
what are the entities responsible physiologically for iron stores?
ferritin and hemosiderin
what is the principal storage form of iron?
ferritin, a “hollow” protein loaded with iron
is ferritin visible by routine microscopy?
no
is hemosiderin visible by routine microscopy?
yes
hemosiderin is composed of what?
intracellular granules in iron storing cells - autophagosomes loaded with semidigested ferritin molecules
iron stores may be increased due to ___
hemochromatosis (hereditary, too much iron absorbed or retained) or hemosiderosis (iron overload bc of other systemic or local causes)
what is the function lipofuscin?
“wear and tear” pigment, polymer of oxidized lipids, present in long-lived cells; no real use proven
what is melanin?
naturally occurring pigment normally present in basal layer of skin, retina, and some other ectodermal derived tissues
what is the function of melanin?
absorbs harmful UV light and may be useful as free radical ‘sink’, in neoplasms may indicate malignant melanoma
name the most commonly encountered black pigment in pathology
carbon
what is the main route of ingestion of carbon?
pulmonary
can carbon be seen microscopally? grossly?
yes and yes
what is anthracosis?
permanent condition of black pigment in the lungs, pulmonary lymph nodes, and distant tissues
is anthracosis harmful?
no, as long as surrounding tissues don’t react to inert carbon
what causes tissue calcification?
calcium salts deposit in abnormal, diseased or dead tissues of many types
what are the types of pathologic calcification?
dystrophic type and metastatic type
which type of calcification is more common?
dystrophic
what are the features of dystrophic type calcification?
- more common
- generally localized process, usu. related to some tissue injury
- plasma calcium levels are normal
what are the features of metastatic type calcification?
- less common
- generalized process where there may be calcification of many tissues
- generally related to more systemic derangement of calcium levels (elevated)
what abnormal accumulations can build up in cells?
water, electrolytes, lipids, carbs, proteins
how do water and electrolytes accumulate in cells?
leaking into cells due to vacuole formation or to hydropic swelling, resulting in diffuse waterlogging of entire cell
what is hydropic swelling?
early and often reversible indicator of cell damage
what are the 2 significant lipids that can accumulate in cells?
cholesterol and triglycerides
what is xanthelasma?
soft, yellow-orange like plaques on eyelids or medial canthus (associated with LDL)
how are triglycerides seen in accumulation?
seen grossly as greasy, yellow deposits on diseased organs whose cells are engorged with triglyceride droplets and vacuoles (steatosis) –> most common in liver
kwashiorkor is caused by what type of diet?
low protein, high carb
kwashiorkor results from the lack of what?
protein synthesis, which blocks synthesis and export of LPPs from liver, with retention of lipid components
abnormal deposition or storage of cholesterol can lead to what?
severe disease or may be histologic curiosity only (e.g., foam cells in wall of gallbladder)
what is an example of a carbohydrate accumulant that is seen pathologically?
glycogen, may increase intracellularly in conditions like diabetes or hypoxia but accumulation tends to diffuse
most carbohydrate accumulations can’t be seen as discrete bodies, except for ___ found in the aging CNS.
corpora amylaceae (extracellular, not harmful)
what proteins tend to accumulate and when do they do so?
cytoskeletal proteins may accumulate or condense in a variety of disease states