Section 1
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pathological hyperplasia characteristic to viral infection - papillomaviruses =mass of hyper plastic epithelium
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Cards (178)
Section 1
(50 cards)
pathological hyperplasia characteristic to viral infection - papillomaviruses =mass of hyper plastic epithelium
wart is an example of physiological or pathological hyperplasia?
brown atrophy cellular debris that resists autophagy
lipofuscin
Metaplasia of columnar epithelium (left) to squamous epithelium (right) in a bronchus. Cigarette smoker Normal PCCE replaced by stratified squamous epithelial cells Lack of mucociliary elevator
physiological
atrophy of embryonic structures would be an example of physiological or pathologic atrophy?
increased size of the cell through increased synthesis of proteins and increased myofilaments therefore increasing the force each myocyte can generate ( increasing strength and work capacity of whole cell
whether its hypertrophy of the striated muscle cells or cardiac muscle cells what is being increased?
following an intramuscular hemorrhage (like being hit with a baseball) patient will experience MYOSITIS OSSIFICANS (bone formation in muscle) formation of cartilage / bone / adipose tissue (mesenchymal tissue) in tissue that do not contain these elements
example of connective tissue metaplasia
hypertrophy OR hyperplasia hyperplasia would be breast increased in size due to puberty or mother to new born
hormonal stimulation can result in
hypertrophy ANP (atrial natriuretic peptide; increase Na secretion and decreased blood volume as well as BP) *ANP is down regulated afterbirth but REEXPRESSED IN HYPERTROPHIC cardiac cells
what cellular response re-expresses genes .. example
cell size and intracellular proteins as well as myofilaments
in skeletal muscle cells (or cardiac cells) hypertrophy would cause an increase in...
when stress on a cell causes metabolic derangements or chronic injury intracellular accumulations include; protein, lipid, carb build up
when might you see intracellular accumulations?
hypertrophy muscle hypertrophy switches from alpha isoform of myosin heavy chain to beta isoform of heavy light chain because slower more energetically efficient
what cellular response switches contractile proteins .. example
reduced blood supply
ischemia
biochem and structural alterations
morphologic change
connective tissue metaplasia myositis ossificans = bone formation in muscle
mechanism of atrophy from nutrient deficiency OR disuse *this activates the ubiquitin ligases (ubiquitin attaches to cellular proteins and targets for degradation in proteasomes *and increases proteolysis (like catabolic conditions = cancer cachexia)
ubiquitin proteasome pathway
excess or inappropriate actions of hormones or growth factors acting on target cells
pathological hyperplasia is cause by...
pathological induced by response to androgens - bumpy prostate with START STOP stream - can lead to cancer
benign prostatic hyperplasia is an example of physiological or pathological hyperplasia?
increased number of cells
hyperplasia
heart muscles become enlarged as a form of adaptation and can then become injured if later blood supply to myocardium is inadequate the muscle will first suffer from reversible injury (via cytoplasmic changes but will eventually suffer irreversible injury and die
what will the heart do in response to increased hemodynamic loads .... and if later the blood supply to the myocardium is compromised or inadequate?
cell death can be caused by ischemia, toxins, infection
what is the end result of progressive cell injury
regressive changes occur.. lysis and loss of myofibril contractile elements extreme case= myocyte death occurs overal equates to cardiac failure
when hypertrophy eventually reaches a limit beyond which enlargement of muscle mass is no longer able to cope with the increased burden ...
barret esophagus - shows stratified squamous cells being replaced by intestinal like columnar epithelia METAPLASIA
photo taken from the esophagus
wasting / weakness of body from source of chronic illness
cachexia
cause (genetic vs acquired)
etiology
hypertrophy
what is triggered by an increase in word load
functional consequences
clinical manifestations
decreased workload - atrophy of disuse (like with immobilization or bedrest denervation diminished blood supply
common causes of atrophy include
reduced size of its or organ due to decrease in cell size and cell number
atrophy
Barret Exophagus - GI tract change in the esophagus (which is normally line with stratified squamous) because of acid reflux the esophagus is exposed to gastric acid which burns the epithelial cells causing body to REPROGRAM stem cells in that area into intestinal columnar epithelial cells
example of squamous to columnar metaplasia
undergoing hypertrophy
how do skeletal muscle cells and cardiac muscle cells respond to increased metabolic demands?
adaptive substitution of cells (sensitive to stress) *replaces with cell that is better able to withstand adverse envir REPROGRAMMING stem cells in the damaged area are reprogrammed into diff cell type (therefore this is NOT a change in phenotype of the cell) or PRECURSOR cells diff along new pathway
metaplasia
autophagy.. an adaptive cellular response that may also culminate in cell death
nutrient deprivation triggers..
mechanical sensors (increased work load) growth factors ( IGF-1, FGF, TGF-beta) vasoactive agents (angiotensin II, alpha adrenergic agonists etc)
integrated actions of hypertrophy are...
membrane bound vacuoles with fragments of cellular components (ultimately fuse with lysosomes and are digested)
autophagic vacuoles
calcium deposited at sites of cell death
pathological calcification
pathological
cardiac hypertrophy would be an example of physiological or pathologic hypertrophy?
enlarged cells - resulting in increase in size of resulting organ
hypertrophy
is mostly due to to hormone-induced hypertrophy ( stimulated by estrogenic hormones acting on smooth muscle)
growth of uterus during pregnancy
embryogenesis and maintaining homeostasis
cell death is normal and essential for...
pathological common cause of abnormal menstrual bleeding - can lead to cancer
endometrial hyperplasia is an example of physiological or pathological hyperplasia?
mechanism of development
pathogenesis
barbiturate drugs ( such as alcohol that act as a depressant, increased GABA activity therefore increasing serotonin) in overconsumption of alcohol... hypertrophy of smooth endoplasmic reticulum in hepatocytes = adaptive response in liver where there is an increase in amount of enzymes available to detoxify drugs therefore patients are able to process at a FASTER rate and have less of a response to original stimulus
an example of a sub cellular organelle undergoing selective hypertrophy
physiological
atrophy of the uterus shortly after parturition would be an example of physiological or pathologic atrophy?
physiological
exercise induced hypertrophy would be an example of physiological or pathologic hypertrophy?
physiological
compensatory hyperplasia is an example of physiological or pathological hyperplasia?
physiological like with breast size during puberty or pregnancy or pathological is hormones are inappropriately expressed like with endometrial hyperplasia and benign prostatic hyperplasia
hormonal hyperplasia is an example of physiological or pathological hyperplasia?
pathological characteristic to viral infection - papillomaviruses =mass of hyper plastic epithelium
mucosal lesion is an example of physiological or pathological hyperplasia?
pathological atrophy
marasmus would be an example of physiological or pathologic atrophy?
infection nutrition chemical physical
examples of an acquired disease
increased functional demand or by stimulation by hormones and growth factors.
physiological hypertrophy is caused by...
Section 2
(50 cards)
marasmus - atrophy due to protein deficiency = inadequate nutrition -- autophagy Use of skeletal muscle as a source of energy after other reserves (adipose stores) have been depleted Results in cachexia
caspase 8 and 9
initiator caspases
apoptosis in order to maintain homeostasis - cell loss in proliferating cell populations to maintain a constant number
Immature lymphocytes in the bone marrow leads to
cell canabalism survival mechanism due to nutrient deprivation where cell eats itself and recycles digested contents autophagic vacuoles sequesters cytosol portions and intracellular organelles into autophagic vacuoles then these autphagic vesicles fuse with lysosomes to form a = autphagolysosome then cellular components are digested by lysosomal enzymes HOWEVER leads to intracellular accumulations
Autophagy
healthy cell : Phosphatidylserine is present on inner leaflet of plasma membrane apoptotic cell : phospholipid flips out and is expressed on outer layer of membrane =recognition by several macrophages
healthy cell vs apoptotic cell....
Abnormal endogenous substance accumulates because of defects in protein folding and transport therefore there is an inability to degrade the protein or transport it
Mutated proteins in degenerative disorders of the CNS is an example of what type of intracellular accumulation?
Normal endogenous substance accumulates because of defect in enzyme responsible for degrading it (usually inherited storage diseases)
Tay Sachs is an example of what type of intracellular accumulation?
caspase 8 and 10 - death receptor initiated
capsize of extrinsic pathway for apoptosis
normal ENDOGENOUS substance produced at an adequate or increased rate BUT metabolic rate is decreased = inadequate removal
Fatty change in the liver and reabsorption protein droplets in the tubules of the kidneys is an example of what type of intracellular accumulation?
apoptosis in order to maintain homeostasis - cell loss in proliferating cell populations to maintain a constant number
Thymus that fails to express useful antigen receptors leads to
infarct
a small localized area of dead tissue resulting from failure of blood supply.
endometrial hyerplasia - common cause of abnormal menstrual bleeding Caused by excess or inappropriate actions of hormones or growth factors acting on target cells Endometrial hyperplasia Abnormal hormone-induced hyperplasia Common cause of abnormal menstrual bleeding
endometrium
restoring the blood flow to ischemic tissues, oxygen and nutrient deprived tissues, does promote recovery of cells however this reperfused tissue may develop loss of cells in addition to the cells that are irreversibly damaged by ischemia... *further damage ensues during reoxygenation which increases generation of reactive oxygen and nitrogen species = damage because cellular antioxidant defense mechanisms are compromised by the preceding ischemia resulting in an accumulation of free radicals *Ca2+ may also enter reperfused cells - damaging various organelles further increasing free radical production *inflammation *complement system
how can ischemia-reperfusion cause further injury?
Growth Factor Deprivation
Neurons deprived of nerve growth factor die by apoptosis would be an example of what type of apoptosis
decrease in oxygen tension within cell (*loss of oxidative phosphorylation) *decreased generation of ATP failure of Na pump = influx of Na and water (therefore cell SWELLS) and a efflux of K **influx of Ca *progressive loss of glycogen *decreased protein synthesis
ischemic cell injury will cause... sequence of events.
toxic chemical related to dry cleaning industry 30-40+ years later patients will develop renal cell carcinoma because of cytochrome p450 converting CCl4 to CCl3 (a free radical) causing lipid peroxidation and damages cellular structures
CCl4
apoptosis since they have served their useful purpose
Lymphocytes at the end of an immune response..
Abnormal endogenous substance accumulates because of defects in protein folding and transport therefore there is an inability to degrade the protein or transport it
Accumulation of mutated α1-antitrypsin in liver cells is an example of what type of intracellular accumulation?
apoptosis since they have served their useful purpose
Neutrophils in an acute inflammatory response post fulfilling tasks will undergo
caspase 3 and 6
executioner caspases
normal apoptosis caused by hormonal withdrawal Atresia is a condition in which an orifice or passage in the body is abnormally closed or absent.
Ovarian follicular atresia in menopause is an example of
normal apoptosis caused by hormonal withdrawal
Endometrial cell breakdown during the menstrual cycle is an example of
ischemia decrease in supply of oxygen and nutrients (cause of reduced blood flow) usually due to mechanical obstruction like a plaque in arterial system and reduced venous drainage can lead to hypoxia
ischemia
normal apoptosis caused by hormonal withdrawal
Prostatic atrophy after castration is an example of
converted to a toxic chemical by the liver during detoxification resulting in cell injury
Acetaminophen
cytoplasm sometimes in nucleus
Location of Abnormal Intracellular Accumulations (usually)
DNA Damage
Exposure of cells to radiation or chemotherapeutic agents would be an example of what type of apoptosis
cytochrome p450 mixed function oxidases -smooth ER of liver and other organs causing membrane damage and cell injury -free radicals and subsequent lipid peroxidation
usually toxic chemicals are not initially toxic to body but are converted by _____ in the body causing injury
apoptosis leading to pathological atrophy in pancreas, kidney and parotid gland
duct obstruction causes what reaction in parenchymal organs?
Apoptosis of an epidermal cell in an immune reaction. The cell is reduced in size and contains brightly eosinophilic cytoplasm and a condensed nucleus.
benign prostate hyperplasia induced by response to androgens
aerobic metabolism is compromised *glycolytic substrates are exhausted = compromising the delivery of substrates for glycolysis = glycolysis is inhibited = accumulation of metabolites
what are consequence that occur due to an ischemic hypoxic injury
Physiologic hypertrophy of the uterus during pregnancy. A, Gross appearance of a normal uterus (right) and a gravid uterus (removed for postpartum bleeding) (left). B, Small spindle-shaped uterine smooth muscle cells from a normal uterus, compared with C, large plump cells from the gravid uterus, at the same magnification.
caspase 9 - mitochondrial damaging pathway via increasing mitochondrial permeability
caspase of intrinsic pathway for apoptosis
ROS reactive oxygen species type of oxygen derived free radical produced normally in cells (during mitchondrial respiration and energy generation) produced in large amounts by leukocytes (Neutrophils and macrophages)
ROS
pathological effects of free radicals 1. lipid peroxidation in membranes 2. oxidative modification of proteins 3. lesions in DNA
pathological effects of free radicals
wart - Papillomaviruses masses of hyperplastic epithelium : characteristic of VIRAL INFECTION
Growth Factor Deprivation
Lymphocytes that are not stimulated by antigens and cytokines would be an example of what type of apoptosis
HYPERPLASIA : Proliferation of the glandular epithelium of female breast Puberty Pregnancy
photo of lobules in the breast
normal apoptosis caused by hormonal withdrawal
Regression of the lactating breast after weaning is an example of
apoptosis induced by the virus (adenovirus or HIV) or due to human immune response (viral hepatitis
viral hepatitis or viral infections in general will cause what response in the human body
Atrophy. A, Normal brain of a young adult. B, Atrophy of the brain in an 82-year-old male with atherosclerotic cerebrovascular disease, resulting in reduced blood supply. Note that loss of brain substance narrows the gyri and widens the sulci. The meninges have been stripped from the right half of each specimen to reveal the surface of the brain.
apoptosis in order to maintain homeostasis - cell loss in proliferating cell populations to maintain a constant number
Epithelial cells in intestinal crypts leads to
toxic liver injury =chemical (toxic) injury to body due to pharmaceuticals causes free radical formation, lipid peroxidation, and cellular membrane damage
Most frequent reason for terminating therapeutic use or development of a drug
Most characteristic feature of apoptosis... chromatin condensation -aggregates peripherally into dense masses other signs are cell shrinkage, nucleus fragmentation, dense cytoplasm, tightly packed organelles, cytoplasmic blebs and apoptotic bodies and finally phagocytosis of these apoptotic or cell bodies via macrophages
Most characteristic feature of apoptosis...
B lymphocytes in germinal centers leads to apoptosis in order to maintain homeostasis - cell loss in proliferating cell populations to maintain a constant number
B lymphocytes in germinal centers leads to
degenerating cellular membranes seen within the cytoplasm (in autophagic vacuoles) or extracellularly seen in reversible and irreversible injuries as part of cytoskeleton dispersion process
myelin figures
1. normal ENDOGENOUS substance produced at an adequate or increased rate BUT metabolic rate is decreased = inadequate removal -fatty change in liver (drinking in excess) 2. Abnormal endogenous substance accumulates because of defects in protein folding and transport therefore there is an inability to degrade the protein or transport it -α1-antitrypsin 3. Normal endogenous substance accumulates because of defect in enzyme responsible for degrading it (usually inherited storage diseases) -tay sachs 4. Abnormal exogenous substance is deposited and accumulates because the cell does not have machinery to metabolize or ability to transport the protein - carbon or lead particles
4 types of abnormalities leading to intracellular accumulations
ischemia tends to cause a more rapid and severe cell and tissue injury than hypoxia would in the absence of ischemia also hypoxia is just reduced oxygen?
what is difference between ischemia and hypoxia
Growth Factor Deprivation
Hormone-sensitive cells deprived of the relevant hormone would be an example of what type of apoptosis
Section 3
(50 cards)
Deposition of calcium salts in otherwise normal tissues Hypercalcemia secondary to some disturbance in calcium metabolism
Metastatic Calcification
Xanthomas -intracellular accumulation of cholesterol within macrophages (acquired or hereditary hyperlipidemic states)
clusters of foamy cells in subepithelial connective tissue of skin and tendon
Cholesterolosis
focal accumulation of cholesterol-laden macrophages in lamina propria of gal bladder
Metastatic Calcification
cholesterolosis -cholesterol laden macrophages (foamy clusters) this is gal bladder cholesterolosis
"strawberry seeds on gal bladder" is trigger phase for
mononuclear phagocytes in liver, spleen, bone marrow, lymph nodes scattered macrophages throughout other organs
Systemic hemosiderosis
Cellular Aging Regulated process Influenced by a limited number of genes Associated with definable mechanistic alterations
*Decreased cellular replication *Accumulation of metabolic and genetic damage are factors of...
Prussian blue stain that is specific for Fe = Iron pigments = hemosiderin
Dystrophic calcification Local deposition in dying tissues Normal serum levels of calcium Absence of derangements in calcium metabolism Encountered in areas of necrosis Coagulative, caseous, or liquefactive type
Dystrophic calcification
Hemosiderin granules - finely distributed NOT peripherally located H+E stain showing golden-brown, finely granular pigment.
hyaline change =amorphous pink deposition - alteration within cells or in extracellular space H+E of glomerulus : homogenous, glassy, pink appearance hyaline change is not permanent, can be revered and is caused by many different things
Cholesterolosis = "strawberry seeds on gal bladder" -cholesterol laden macrophages (foamy clusters) this is gal bladder cholesterolosis
a balance between... damage resulting form metabolic events within the cell && counteracting molecules responses that repair the damage
Cellular life span is determine by...
Hemoglobin derived golden yellow brown, granular or crystalline pigment major form of Fe represents aggregates of ferritin micelles Seen normally in mononuclear phagocytes of the bone marrow, spleen, and liver (actively part of RBC breakdown)
Hemosiderin
Excessive intracellular deposits of glycogen **Seen in patients with an abnormality in either glucose or glycogen metabolism Appear as clear vacuoles within the cytoplasm Dissolves in aqueous fixatives Tissues are best fixed in absolute alcohol Staining with Best carmine or the PAS reaction Rose-to-violet color to the glycogen
Lipid accumulation : fatty change - usually associated with the liver because that is where majority of fat metabolism occurs most likely a heavier organ (2-4x larger)
Bright yellow, soft, greasy gross examination of an organ would show? what other characteristics would you observe?
fatty change =abnormal accumulations of TG within parenchymal cells *seen in liver because it is the main organ associated with fat metabolism *also occurs in kidneys, heart and muscle
Steatosis
Pigmentation Carbon (coal dust) Ubiquitous air pollutant of urban life Accumulations blacken the tissues of the lungs (anthracosis) and the involved lymph nodes
Melanin
The only endogenous brown-black pigment
lysosomal storage disorder caused by mutations effecting an enzyme involved in cholesterol trafficking -leads to cholesterol accumulation in multiple organs
Neiman Pick disease - type C
Adipose requires a different stain inorder to be shown : Requires the avoidance of fat solvents commonly used in tissue preparation Sudan IV or Oil Red-O
why do adipocytes appear clear in H+E stain?
Xanthomas
Abnormal exogenous substance is deposited and accumulates because the cell does not have machinery to metabolize or ability to transport the protein
Accumulations of carbon particles and nonmetabolizable chemicals (silica) is an example of what type of intracellular accumulation?
Cholesterolosis = "strawberry seeds on gal bladder" -cholesterol laden macrophages (foamy clusters) this is gal bladder cholesterolosis
most common cause in developed countries is alcohol abuse or non-alcoholic fatty liver disease due to diabetes or obesity other causes toxin protein mulnutrition diabetes mellitus obesity
what are causes of steatosis
melanin
dystrophic calcification and metastatic calcification dystrophic (necrotizing tissue with normals Ca levels) metastatic (deposition of calcium salt in normal tissues usually with disturbance in Ca metabolism)
two forms of pathological calcifications
a striked appearance of yellow myocardium in a gross examination with alternating bands of darker red-brown, uninvolved myocardium (tiger striped effect)
Lipid accumulation in the heart would reveal
Dystrophic calcification of the aortic valve aortic valve in a heart with calcific aortic stenosis It is markedly narrowed (stenosis). The semilunar cusps are thickened and fibrotic, and behind each cusp are irregular masses of piled-up dystrophic calcification.
hyaline change =amorphous pink deposition alteration within cells or in the extracellular space -center is a blood vessel H+E : homogenous, glassy, pink appearance *amorphous = no cells
Endogenous pigment = Lipofuscin = Insoluble pigment " lipochrome " or " wear-and-tear pigment " Telltale sign of free radical injury and lipid peroxidation Yellow-brown, finely granular cytoplasmic often perinuclear, pigment in tissue sections Prominent in the liver and heart Aging patients / severe malnutrition and/or cancer cachexia
Lipofuscin
reabsorption droplets in the proximal tubules causing intracellular protein accumulations
Renal diseases associated with protein loss in the urine are likely due to ..
intracellular accumulation of cholesterol or cholesterol esters appears foamy aggregates in the intimate
Atherosclerosis
lipofuscin
Endogenous pigmentation that is prominent of heart and liver...
Hemosiderin
pigmentation seen normally in mononuclear phagocytes of bone marrow, spleen, and liver
normal major pigment found in bile derived from hemoglobin but has NO Iron
Bilirubin
fatty liver High-power detail of fatty change of the liver (lipid accumulation). In most cells the well-preserved nucleus is squeezed into the displaced rim of cytoplasm about the fat vacuole.
Localized, pigmentation of the skin Pigments inoculated are phagocytosed by dermal macrophages
Tattooing
dystrophic calcification
what is associated with thermos of advanced arthersclerosis
Hemosiderin
pigmentation that is actively part of RBC breakdown?
glycogen accumulations stains best with carmine or with PAS : rose to violet color to the glycogen "crinkled up tissue paper" & "grainy and wrinkled" seen in patients with abnormality in either glucose or glycogen metabolism
Hemosiderin - iron pigmentation within cells cytoplasm Visualized in tissues using Prussian blue histochemical reaction *Localized breakdown of red cells
Protein reabsorption droplets in the renal tubular epithelium= intracellular accumulations of protein the grainy pink part are the protein resorption droplets (could be from protein misfolding, enzyme disorder; depends on patient) the purple circles are hepatocytes and dark spots within are nuclei
Emphysema =Defective intracellular transport and secretion of critical proteins
α1-antitrypsin deficiency
clusters of foamy cells in subepithelial connective tissue of skin and tendon -intracellular accumulation of cholesterol within macrophages (acquired or hereditary hyperlipidemic states)
Xanthomas
focal accumulation of cholesterol-laden macrophages in lamina propria of gal bladder
Cholesterolosis
lipofuscin
non-hemoglobin derived brown-black pigment formed by enzyme tyrosinase catalyzing the oxidation of tyrosine to dihydroxyphenylalanine in melanocytes (The only endogenous brown-black pigment)
Melanin (formation?)
Bilirubin
Melanin Lipofuscin Hemosiderin
Endogenous pigments
Section 4
(28 cards)