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186 Cards in this Set

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  • Back
What's the difference between hyperplasia and hypertrophy?
hyperplasia is increased numger of cells and hypertrophy is increased size of cell
What is metaplasia?
Change from one cell type to another. Ex. smokers change esophageal squamous epithelium to columnar OR endocervical chronic irritation replace columnar w/ squamous--better suited
What are abnormal changes in cellular components called? What can this lead to?
Dysplasia. Can become PRE-cancer.
What is the difference between dysplasia and metaplasia?
metaplasia is organized while dysplasia is not and can lead to cancer
What are the nuceli like in dysplastic cells?
nuclei are irregular in dysplastic cells
When a normal cell undergoes excess physiologic stress what can happen to it?
either it will adapt or die. When injury is reverisble and is chronic it adapts and when acute it dies
What are forms of lethal injury?
apoptosis or necrosis
What does a normal cell dependent on in order to remain viable?
needs genetic program for differentiation and metabolism, constraints of neighbor cells, metabolic substrates
What are forms of adaptation
hypertrophy and hyperplasia OR atrophy, dysplasia, metaplasia
What causes atrophy? (7)
disuse, loss of innervation, diminished blood supply, inadequate nutrition, loss of endocrine stimulation, aging, pressure
What are the steps in clinical diagnosis?
etiology (cause), pathogenesis (mechanism of events), disease, clinical signs (clinician) and symptoms (patient), lab tests, diagnosis
Are there any types of physiologic atropy?
Sure, uterus after parturition
What is lipofuscin commonly associated with?
atrophy, not diagnositic of atrophy, but often associated with
What causes atrophy?
protein synthesis an dprotein degradation
What is atrophy commonly associated with?
lipofuscin and autophgic vacuoles
What is lipofuschin?
residual bodies (byproduct of protein digestion)associated with atrophy and aging
Atrophy results from an imbalance in what?
in protein synthesis and degradation with lipofuscin as a result
How does atrophy occur?
lysosomes, protein degradation

ubiquitin proteasome pathwya of protein degradation. (catabolic cancer cachexia)
Why does hypertrophy result? What are ex of physioloical and pathological?
hypertrophy due to increased demand which leads to increased functional proteins.

physio--uterus and breast in pregnancy

patho--heart mm adaptation( alpha myosin replaced by beta myosin heavy chain, TGF, beta)
Give some physioloical and pathological examples of hyperplasia?
physio--fremal breast at puberty and pregnancy AND liver after hepatectomy

patho--(may be precancerous) excessive hormal stimulation--endometrium. Effects of growth factor on target cells
What is a key factor in metaplasia?

What is the trade-off in metaplasia?
reprogramming stem cells. Ex. squamous to columnar adult cells.

undersirable: loss of important function at expense of durability
What (7) factors can cause cell injury or death? etiologic agents
1. hypoxia and ischemia
2. physical agents--burn, cold, radiation
3. chemicals and drugs
4. micorobiologic agents
5. immunologic derangements--autoimmunity, drug rxn
6. genetic derrangements
7. nutritional imbalances--anorexia and obesity
What are the major biochmeical mechanisms for cell injury?
interfere with endogenous substances or enzymes--leads to decreased ATP

disruption of ETC or TCA cycle
What happens in order to kill a cell?
increased o2 radical, ATP depleted, increased cytosolic Ca and ruined Ca homeostasis.

irreversible mitochondrial damage

cytochrome c initiates cascade to apoptosis
When the cell membrane changes reversibly what are the signs?

How do you know the damage is irreversible?
cell swelling, cytoplamic blebs, blunitng of microvili, myelin forms, loosening of intracellular attachements.

Irreversible only when the membrane breaks
What are the signs of reversible mitochonidrial damage?

mitochondrial swelling, matrix condensation

Irreversible--vacuoles swell, bizarre forms, amorphous densities, Ca deposits, membrane rupture
What are the signs of reversible ER damage?

damage to ER results in decreased protein synethesis

reversible--dilation, ribosomes detatch, polysomes dissociate

Irreversible--progressive fragmentation and lysis of ER
What are the signs of reversible lysosomal damage?

reversible--swollen, no leakage of enzymes

irreversible--markedly swollen or ruptured and disappeared, leaked enzymes
What morphological changes can be seen by light microscope?
cytoplasmic, nuclear, nucleolar changes
What are the signs of reversible cytoplasmic damage?

cellular swelling

irreversible--cytoplasmic eosinophilia (high eosinophil count), homogeneous, eosinophilic globules (swollen mitochondria), cellular calcification
Which cellular sites are particularly vulnerable to injury?
cell membrane, aerobic resp, protein synthesis, genetic apparatus.
What is cell response to injury dependent on?
type of injury, duration and severity
What do consequences of injury depend on?
type, state, adaptability of injured cell
Wehn does a morphologic change become apparent?
only after derangement of a critical biochemical system
What are three effects of reversible types of cell injury?
pallor (compression of capillaries), increased weight (due to cell swelling), increase in turgor (due to increase in size)
What are the most common forms of cell injury?
ischemic and hypoxic, free radical induced injury, toxic injury
Why do changes take place in the cell membrane when in hypoxia? What is the result?
o The disruption of mitochondrial aerobic respiration leads to the absence of ATP, which leads to changes in the plasma membrane. Changes in membrane lead to increased wnzyme activity, decreased glycogen and decreased pH until can't do glycolysis. Disrupt ER (protein synthesis)
How long does it take to get reversible changes after ishemic/hypoxic injury? When will irreversible injury result?
Only 60 sec. After 30-40 mins irreversible damage begins (so with heart attack, the quicker they get to the hospital to stabilize the more cells can be saved from IRreversible damage)
What happens to Na levels during ischemic and hypoxic injury?
influx is greater, leads to swelling because water and Ca+2 influx w/ Na. [K efflux]
In persistent hypoxia what IRreversible injuries occur?
In mitochondria--SEVERE swelling, amorphous densities.

plasma membrane--extensive damage, leakage of enzymes!! Serum is indicator.

Lysosomes--swelling and activation of enzymes for digestion
What is coagulative necrosis?
refers to cells that have maintained their cell membranes/borders but have lost their nucleus, appear more acidophilic
Describe the how a Reperfusion Injury occurs and what results.
increase oxygen on reperfusion to try to reverse hypoxia/ischemia. Thereby increase O2- (superoxide radical). Free radicals promote mitochondrial permeability transition. CK's recruit PMN's w/ reperfusion
What is an autocatalytic rxn as far as free radicals are concerned?
increase in free radicals
What can cause free radicals?
radiation, inflammation, oxygen toxicity, chemicals, reperfusion injury
What protects against free radicals?
superoxide dismutase, glutathione peroxidase, Vitaman A, E, C, catalyase in peroxisomes decomposes H202, spontaneous decay to H202 and o2.
What are the mechanisms for chemical injry?
direct combination with the cell components (mercuric chloride and cyanide directly poisons mitochondrial enzymes)


the injury might be inactive until converted to free radicals by P450 in the ER (CCl4 and acetaminophen)
How does CCl4 cause injury?
§ Free lipid radicals are unable to attach to proteins to form lipoproteins, and thus, they build up within the cells and lead to a fatty liver because of enlarged hepatocytes
How does acetaminophen cause damage?
High or moderate amounts of acetaminophen leads to massive hepatic necrosis b/c of overuse of glutathione molecules (depletion) Time: 3-5 days
What is the morphology of coagulative necrosis?
see outline of cell, no nucleus, protein denaturation. ischemic EXCEPT in the brain.
What are the general features of necrosis?
morphologic expression of cell death, results from a SLOW process (hours), digestion of cell, and denaturationof protein, symptoms and enzymes in serum.
When is liquefactive necrosis common? What are its features?
common in most infections and ISCHEMIC brain infarcts! ENZYMATIC digestion occurs. This happens in stroke, and ischemia of the brain. Appears smooshy. brain can become cystic.
What type of necrosis is common in TB patients?
Caseous. Looks cheezy. No cell outlines, amorphous material
What are symptoms of enzymatic fat necrosis?
Occurs in pancreatitis, Suponification: bubbles of fat in tissue due to combining of fat w/ Ca
o areas of fat destruction, result of release of activated pancreatic lipases into pancreas and peritoneal cavity
What are the types of gangrene and what are types of necrosis are they due to?
Dry Gangrene: occurs b/c of coagulative necrosis
Wet Gangrene: occurs b/c of liquifactive necrosis
Which is faster: necrosis or apoptosis?
What is apoptosis?
cell death w/o inflammation--not as morphological as necrosis. Also called programmed cell death
What type of cell is necessary for apoptosis?
phagocyte, engulf apoptotic bodies from dying cell
What are some causes of apoptosis?
inhibition of growth hormones, death of immune cells, cytotoxic Tcell injury, viral disease, cell death in tumors, cell deletion in proliferating cells (cancer research looking at this)
What are the steps of apoptosis?
1. signaling pathway to initiate
2. control/integration (promote or stop apoptosis) checkpoint.
3. execution phase: requires C-aspase (C for cysteine and aspase--to cleave after aspartic (asp) acid residues
4. execution: caspases to disrupt cytoskeleton by clevage of cytoskeletal and nuclear matrix proteins.
Decide which of the following is a symptom of necrosis or of apoptosis:
inflammation, fragmentation, cell shirinking, cell swelling, enzymatic digestion, physiologic, pathologic.
necrosis--inflammation, swelling, pathologic, enzymatic digestion, plama membrane disrupted.

apoptosis-cell shrinking, intact plasma membrane and cell contents, physiologic
What is the difference between intrinsic and extrinsic apoptosis? How is cancer related to apoptosis?
intrinsic uses BCl2 family (inhibition of apoptosis or BCl2 leads to cancer)

extrinsic-uses FAS membrane bound receptor. Involved in the removal of tumor cells. Triggers apoptosis.
What happens when apoptosis is inhibited? What if it is increased?
leads to cancer. If increased then leads to ischemic injury, virus induced lyphocyte depletion, neurodegenerative diseases.
What are forms of subcellular repsonse to injury?
lysosomal, SER, mitochondria, cytoskeleton
What is the difference between autophagy and heterophagy? What structure performs these?
autophagy w/in lysosome; heterophagy outside of lysosome
What causes lysomal storage diseases? Is this from a normal or abnormal exogenous or endogenous?
disfunction in enzymes, leads to lack in transport, packaging and secretion. Normal OR Abnormal endogenous substance.
What causes fatty liver disease? Is this the same as stromal fat?
normal endogenous substance because of abnormal metabolism. Fat is a normal thing, but not in the liver at high rates. No--stromal is normal, physiological; fatty liver is pathogenic
Is fatty liver reversible or irreversible?
Reversible. afatty liver to alcoholic hepatitis to cirrohsis.
What is the medical term for fatty liver?
What is the mitochondrial subcellular response to injury?
hypertrophy, atrophy--occurs in nutritional deficiency w/ alcoholism, myopathy, oncocytomas
Why does drug tolerance increase as a response to subcellular injury?
the SER increases tolerance because of p450 adaptation to meds, alcohol.
What are signs of cytoskeletal injury? What disease can result?
chediak-higashi, mallory bodies, neurofibrillary tangle (alzheimers)
If cytoskeleton is damaged, what will the effect be on the thin filaments, microtubules, and intermediate filaments?
thin filaments--actin, myocin, leukocyte movement impaired.

microtubules--sperm motility maybe affected. Leukocyte migration, phagocytosis, mitotic spindle.
Intermediate filaments--cells would fall apart. neurofibrillary tangle leads to alzheimers and mallory bodies formed.
Which portions of the cytoskeleton are targeted by drugs?
thin filaments and microtubules are targeted. Colchicine targets microtubules
What type of pigments can be accumulated?
exogenous--C and tatoos

endogenous--lipofuscin, melanin, hemosiderin (hb to iron to ferritin to aggreg), bilirubin (hg to bilirubin and Fe)
What effects can intracellular accumulation of bilirubin have? What about in children?
jaundice, obstructive liver disease (greenish brown globular deposits in liver), hemolytic disease of newborn (bilirubin encephalophthy= kernicterus)
What are the two types of calcification and what's the difference?
dystrophic and metastatic. Difference is that dystrophic is local and metastatic is systemic.
Where is dystrophic Ca. found? What is the Ca serum level?
dystrophic= local. areas of necrosis, athrosclerosis, aging, damaged heart valves. normal Ca level in serum
Give some exs of metastatic Ca. What is the Ca serum level?
hyperPARAthyroidism, vitamin D intox, systemic sarcoidosis (lymph), metastatic cancer. Serum Ca will be off!
Is hyalin change specific or non-specific? What does it look like? What are the types of accumulation?
non-specific. homogeneous, glassy, pink. Extra and intracellular hyalin accumulation.
Give an ex. of intracellular hyalin cartilage. Extracellular?
intracellular--accumulation of proteins, russel and mallory bodies. Extracellular: long standing htx/DM (diabetes mellitus): arterioles-bm. amyloid: fibrillar protein deposits = enzymatic fat necrosis (note: amyloid is amorphous protein buildup found in alzheimers)
What factors effect aging?
telomerase activity (length of telomere), genetics, environmental
How many units of standard deviation away from the mean is the "normal" range?
The mean ± 2 S.D. = 95% of the population studied
What does the "normal" range assume?
assumes a gauss curve.
If you perform more than 1 lab test will you be more or less likely to see an abnormal result in a healthy population?
What are some non disease factors that could cause a value to be outside of the "normal range"?
genetic, interindividual, racial, ethnic
physiologic, intraindividual, age, sex, etc.
drug influence ( in vivo or in vitro effect)
specimen collection (tourniquet, hemolysis)
specimen handling (transport time, storage time, temperature)
analytical factors (test methodology)
What is indicated when subsequent values of a test are >± 3 SD?
unlikely due to methodology alone, could be due to equipement, etc
What is the difference between sensitivity and specificity?
sensitivity is the + WITH the disease. selectivity is the - without the disease.
What is the difference between predictive values of + and - tests? How are they calculated?
predictive value:

positive: true positive/all positives (true positive + false positive)

negative: true negative/all negatives (false neg and true neg)
How do you calculate sensitivity?
selectivity is # True +/total of those WITH the disease
How do you calculate specificity?
specificity is # true - / total of those w/o the disease
if a test is NEGATIVE what can be ruled out?
That the person has the disease
Predictive value increases with what?
with prevalence/incidence
What effect does prevalence have on sensitivity? specificity? true positives? false negatives? true negatives? false positives?
no change for sensitivity and specificity.
FN and TP increase, TN and FP decrease. i.e. a higher prevalence of disease leads to a better predictive value and a better test.
What is prevalence?
# people w/ disease at point in time.
What are the three types of tests?
screening, diagnostic, multiphastic tests
What are characteristics of a screening test?
asymptomatic patients,
a single + test identifies high % with disease
the - test virtually rules out disease,
the disease should have high prevalence,
untreated dx should have fatal outcome or lead to great disability,
test should be simple and economical,
test should not be harmful or objectionable
What are the characteristics of a diagnostic test?
higher specificity and predictive value than screening tests,
distinguishes those with and without disease i.e., is definitive,
requires costly and sophisticated procedures,
not suited for mass screening
What are the characteristics of a multiphatic test?
testing for MULTIPLE serum parameters,
small serum sample,
low cost/patient,
not indicated in asymptomatic population,
perform better in symptomatic patients,
lower cost than when performed individually
2nd-order tests already included
What yields the best cut off or referent value?
one with HIGHEST SENSitivity and LOWEST false positive rate
Deep-seated pyogenic infection of the skin and subcutaneous tissues, usually arising in several contiguous hair follicles, with formation of connecting sinuses; often preceded or accompanied by fever, malaise, and prostration
inflammation of the soft or connective tissue in which a thin, watery exudate spreads through the tissue spaces.
a collection of pus in a body cavity (especially in the lung cavity)
--In humans, erysipelas is a group A streptococcal infection of the skin resulting in inflammation of skin and underlying tissues. It is a form of cellulitis. (Erysipelas is also the name given to an infection in animals caused by the bacterium Erysipelothrix rhusiopathiae. Infection by Erysipelothrix rhusiopathiae in humans is known as erysipeloid.)
What are the 5 cardinal signs of acute inflammation:
loss of function
What causes the 5 cardinal signs of acute inflammation?
rubor/calor due to hypernemia
dolar due to pressure on n ending
tumor due to edema b/c of exudates
loss of function due to tissue injury or to pain due to inflammation
What happens when vascular permeability is increased?

What is the difference between transudate and exudate?
Transudate—normal ultrafiltrate is replaced by exudates which contains high protein due to increased pore size.

Exudates may contain bacteria, fibrin, purulent, catarral. Transudates do not.
What happens if the lymph system tries to remove exudates?
Spread of bacteria. Possible: lymphangitis (lymphatics) or lymphadenitis. (node)
What are the 3 time related patterns of increased vascular permeability?
a. immediate transient response—30-60 mins after injury, controlled by chemical mediators
b. immediate-sustained response—severe tissue injury w/ endothelial cell sloughing, all levels of microciculation affected. Permeability is increased due to direct damage.
c. Delayed prolonged—common, not well understood. Xray, UV, bacteria, thermal, hypersensitivity are causes. Sunburn good ex. lasts for hrs/days. Involves VENULES AND CAPILLARIES, possible direct endothelial injury by initial stimulus.
What causes rouleaux formation?
Aggregation in CENTER of RBC’s after injury. Looks like stack of pennies.
Where are WBC’s found when rouleaux is formed?
In periphery, b/c RBC’s invaded the center where the WBC’s used to flow freely
How do WBC’s get to an inflammatory tissue? What happens at each step?
1. Margination: In normally flowing blood in venules, RBC’s are confined to a central axial column, displacing the leukocytes toward the wall of the vessel.

1st P-selectin then E-selectin:bind to silated-Lewis X molecules on surface of circulating WBC’s to them them down and marginate.

Cells are rolling, integrins (heterodimers on surface cells) recognize and bind to small sites 3AA’s—Arginine, glycine, aspartate. These will bind with ICAM and VCAM.

2. Pavementing- WBC’s attach to vessels . ICAM and VCAM (intracellular adhesion molecule and vascular cell adhesion molecule) both allow for dramatic shape changes.

3. Adhesion and transmigration
By now, WBC’s conformational change allows to move through pores and across the basement membrane to the extravascular space to reach the tissues.
. How doe RBC’s get out of the blood vessels?
Passively thru leaky blood vessels behind the WBC’s
How long does it take for Neutrophils to get to injured tissue?
6-24 hrs
How long does it take for monocytes to get to the infection?

What does this mark?

What changes occur in a monocyte when it gets to injured tissue?
Moncytes—24-48 hrs. This marks beginning of chronic inflammation . Monocytes change to macrophages by increasing in size, lysosmal content, and phagocytic activity.
What is chemotaxis and why is it so important?
Chemotaxis is movement of cells by a chemical gradient. This is important in the inflammation response b/c large #’s of WBC’s are brought to the site of injury and phagocytosis can occur.
What is opsonization? What is it’s purpose?
Opsonizatoin is the coating of microbes with antibodies, IgG or complement, C3b in order to be more efficiently recognized by receptors on a PMN or macrophage.
When PMN’s and macrophages phagocytize a microbe what happens?
Enzymes leak out and metabolic byproducts get outside the cell which could cause further damage.
. How are organisms killed before phagocytosis?
H202-Myeloperoxidase-halide system. PMS rich in myeloperoxidase (MPO)

Respiratory burst—NADPH involved in forming superoxide, interacts w/ dismutase to form H202.

H202 kills microbes. And does so even more effectively with Myeloperoxidase and halides to form hypochlorous or hypobromous acid.
What do macrophages use to kill microbes?

Are they equally as efficient as PMNs?
No, they are less efficient than PMN’s. Use lysozyme (muramidase) and lactoferrin, and radical—NO. relaxes smooth mm, reduce platelet adhesion. Uncontrolled NO leads to septic shock
Name some of the genetic disorders of PMN’s
diminished #’s of granulocytes= neutropenia
leukocyte adhesion def—LAD1 and LAD2 defective due to mutations in beta chain of integrin.
Diminished #’s receptors for chemotaxsis. (IL8 and C5a receptors)
Inadequated phagocytosis—actin dysfunction syndrome
Chronic granulomatous disease(CGD)—def in NADpH ocidase deficiency. Respiratory burst is messed up, microbes aren’t killed.
PMN granules—Chediak-Higashi syndrome
Which diseases result from problems with Leukocyte

1. adhesion

2. chemotaxis

3. phagocytosis?
Chemotaxis—burns, DIABETES, malignancy
Phagocytosis—sepsis, malnutrition
What is the triple response?
First get a red line (local small blood vessel dilation). Next get a bright flare (arteriole dilation caused by local axon reflex). Finally get edema (increased permeability) and a pale wheal
. What mediates vasodilation? In humans?
Serotonin and histamine—his more in humans. Also, aracodonic acid and platelet activating factors
What are the 2 pathways that arachodonic acid gives rise to? What do they produce?
Cyclo oxygenase—prostoglandins-PG, prostocyclins (PC), and thromboxanes Tx

Lipo-oxygenase-leukotrienes LT
What do products of arachodonic acid pathways do?
All are chemical medators of inflammation
Effects are local
. Describe prostaglandin E, PGE. What is its antagonist?
PGE—vasodilator, enhances bradykinin for pain
What do prostacyclins do? What does it compete with?
PC—endothelial cells dilation, increase permeability. Competes w/ throboxane A (a vasoconstrictor)
What are leukotrienes involved in?
LT—chemotaxis, transient vasoconstriction and increase vascular permeability
What inhibits cyclo oxygenase pathway?
Asprins, NSAIDS
Where do platelet activating factor (acetyl glycerol ether phosphocholine) come form?
AGEPC comes from neutrophils, eosinophils, platelets, basophils, macrophages, vascular endothelium
. What do platelet activating factors (PAF) do?

What types of disorders are they found in?
Cause vasco and broncho constriction at high levels. Low conc. induces vascular permeability and vasodilation. Interesting contradiction.

Also aid in chemotaxis, stimulation of synthesis of PG’s and LT’s

bronchial asthma
Where do lysosomal chemical mediators come from?
What are the functions of acidic, basic, and neutral lysosomal chemical mediators?
Basic--Some act as chemotacitic agents for macrophages, increase vascular permeability, immobilize other granulocytes.

Acidic—degrade bacteria w/in phagolysosomes

Neutral—extracellularly degrade bacteria
What do plasma kinin’s do? Which is most important?
From kallikrein activated by FXII. Produce pain, promote peripheral vasodilation in smooth mm relaxation and contraction of endothelium

Most important—nonapeptide bradykinin
What is C3b?
An opsonin inflammatory mediator of complement system.
What does C5a do?
C5a also important b/c 100 x more potent than C3b. Also part of complement system. Enhances adhesion, chemotactic for neutrophils, macrophages, and eosinophils
. How does activation of the clotting system aid in inflammation response?
Formation of fibrinopepetides—increase vascular permeability and are chemotactics for PMNs. Fibrin liberates fibrin degradation products during lysis and activates the complement cascade
What are the possible outcomes of acute inflammation and which is most likely?
1. complete resolution (most likely)
2. healing by scaring.
3. abscess formation
4 progrssion to chronic inflammation
What is an abscess? What does it indicate?
PMN packed area w liqefacation necrotic tissue. Shows unsuccessful inflammatory response.
What are the main characteristics of acute inflammation?
Short duration, PMNs, exudation of plasma proteins
What are the 3 ways that chronic inflammation occurs?
1. follows acute inflammation
2. response to repeated bouts of acute inflammation (recurrent cholecystitis, pyelonephritis) AKA subacute inflammation. Both types of inflammatory cells
3. insisious low grade smoldering response w/o ever having acute inflammation
Which cells predominate chronic inflammation?
Mononuclear cells—macrophages
How are macrophages able to stick around for so long?
Recruitment from monocytes responding to chemotactic stimuli, local proliferation and ability to survive makes them stay around for longer time.

Rich in hydrolytic enzymes, secretion of cytokines—interferon.
Which type of lymphcytes are present during chronic inflammation?
T and B cells are present in proportion due to the type of inflammatory rxn. Even there in non-immunologic inflammation

Produce cytokines and and activators for macrophages.
What is epithelioid tissue characteristic of?
Granulomatous chronic inflammation. Definitive of GRANULOMA
How does epithelioid tissue stain?
Stain pink in H and E sections
What is found in epitheliod tissue?
Rich in ER, Golgi vescicles—ready for secretion, not phagocytosis.
What other cell might be found in a granuloma?
Giant cells
What are the two types of giant cells and what are the differences? What are the subtypes of giant cells?
Langhans types (nuclei around periphery, like a horse shoe)
Foreign body type—nuclei dispersed all over the cell

Subtypes—asteroid (star like)made of degraded intracellular filaments
and Schaumann bodies—protein w Ca and/or P
Do giant cells do phagocytosis?
No, they don’t have the ability, but they can secrete enzymes.
How could giant cells make you a billionaire?
Figure out how to control chronic inflammation. Giant cells have increased level of alpha antiprotease w/in –control of chronic inflammation
What is an eosinophil?
WBC that digests microorganisms
When are eosinophils found? What do they respond to?
Found in ulcerative colitis, allergic reactions, parasitic infestations, and asthma

Respond to chemotactic agents released by mast cells LTB4.
What do helminthic infections produce? What is a possible side effect?
Helminthic—parasitic. Induce production of eosinophils thru IgE. Release eosinophil granlules. Dangerous b/c could cause damage of human epithelial cells.
What do eosinophils neutralize?
Neutralize histamine, LT, PAF
What are the 2 factors that determine the formation of granulomas?
1. presence of indigestible organisms like fungi or silica and 2. cell mediated immunity (t cell), i.e. produce CDK’s
What is the CDK of critical importance in granuloma formation?
Tumor necrosis factor alpha (TNF alpha)—CDK of importance. W/o granuloma won’t form.
What type of cell is REQUIRED for dx of granulomatous inflammation?
Epitheliod cells
What happens to the center of a TB cell?
Center undergoes CASEOUS NECROSIS= tubercle. Indicitive of TB, doesn’t happen in other granulomas.
What happens to a granuloma once the disease has been treated?
Are most chronic inflammations granulomatous or not?
Most are non-granulomatous.
What are the defining factors of chronic inflammation?
Non-granulomatous, diffuse infiltration of mononuclear cells
What is the difference between repair and regeneration?
Repair forms a scar—replacement w/ CT, regeneration replaces SAME as lost parenchyma cells (parenchyma cells are tissues of an organ)
What type of healing do neurons, cardiac mm undergo?
Repair, cannot regenerate
What types of cell undergo slow regeneration? Fast? What is a characteristic of regeneration cells?
Slow--Liver, kidney, stable cells
Fast—labile cells like surface epithelia, mucosal lining of excretory ducts, glands, transitional cells, hematopoietic cells

Cells w/ ability to regenerate undergo mitosis
What is the result of the repair process?
Loss of function
Is granulotomas tissue the same as granulation tissue.
No! granulation is physiologic. Granulotomas are pathologic
What does granulation tissue look like? Gross and histological.
Appears soft, pink @ gross level, often boggy and edematous due to leaky new jncts
Proliferation of blood vessels and fibroblasts w/macrophages and mast cells—histologically
What is angiogenesis? What are the steps?
New blood vessels by neovascularization. Provide large amt of o2 for wound formation.

First mother vessel basement membrane is degraded, and a new sprout takes place. then existing vascular endothelium MIGRATES into the new sprout, surrounding matrix degraded. PROLIFERATION of vascular endothelium. Fibronectin coats the new outgrowth, new vessel forms a lumen and basement membrane, anatomoses, circuluation.
How do fibroblasts differ w/in granulation and mature tissue?
In granulation tissue they’re making more of the extracellular matrix—non-collagenous glycoproteins, proteoglycans, collagen.
What do activated fibroblasts look like in histologic sections?
Plump and juicy—hypertrophic w/ increased RER, contain myofibroblasts
What is a myofibroblast?
When fibroblasts lose their ability to secrete collagen then they’re myofibroblasts. Found in active fibroblasts—have a muscular coating.
How do macrophages look in granulation tissue?
Hypertrophic b/c of constant remodeling. Stain w/ toudine blue
What are the two types of healing?
First intention/primary union and second intention/secondary union
What is the difference between first and second intention?
First healing between an easy cut—like a surgical cut. The edges aren’t too far away. Heals relatively easily and in a timely manner. No bacterial contamination.
In primary union when do the following form?

Type I and III collagen,


clot forms,

epithelial cells migrate beneath the scab and establish epidermal continuity, PMNs arrive,

New vessels disappear and leukocyte infiltration and edema diminish.

Proliferated fibroblasts migrate and produce procollagen and fibronectin.

Scab falls off.
Type I and III collagen—Day 7

macrophages—Day 3

clot forms—0-1day,

epithelial cells migrate beneath the scab and establish epidermal continuity—1-2 days,

PMNs arrive 0-1 day,

New vessels disappear and leukocyte infiltration and edema diminish 1-2 weeks

Proliferated fibroblasts migrate and produce procollagen and fibronectin –Day 4.

Scab falls off—1-2days.
Describe timeline of healing by 1st intention
0-1 day—Clot forms, scab forms PMN’s come, fibroblast proliferate

1-2 days—epith cell migrate benath the scab, establish epithelial continuity, secrete proteolytic enzyme, dissolve bottom of scab, it drops off

Day 3—macrophages in. PMN’s gone. Granulation fills in incisional space. Collagen synthesis, thickening of epidermis.

Day 4—fibroblasts from procollagen and fibronectin

Day 5—incidsional sp filled w/ vascular granulation tissue—now keratinized

1 week—collagen synthesis maxed out. Actin fibrils condense into bundles. Beginnings of cell matrix appears.

9 days—extracellular matrix accumulated. Fibroblasts w/in wound lose collagen synthesis=myofibroblasts

1-2 weeks—new vessels disappear, leukocyte infiltration and edema diminish. Tissue looks pale (blanched). Tensile strength low. Wound contraction occurs, fibroblasts undergo apoptosis L

1 months—epithelium totally remodeled. Cellular CT, normally overproduction of collagen causing hypertrophied scar.

Months-Years—maturation of scar continues. Collagen Type III replaced by Type I. Scar tissue remains a little weaker than it was prior to injury
Why can’t a timeline be placed on second intention?
Don’t know size of wound and how long it will take to come together. Dependent on degree of damage.
What is the process of second intention like?
Granulation tissue covers wound, epithelial cells migrate from wound edges, granulation tissue contracts via myofibroblasts, pulling skin margins so reduce the wound opening by 70%, then follows 1st intention
What happens if exudates gets into a wound? Describe resolution.
An inflammatory response may develop extensive exudates that fill in tissue spaces. W/o necrosis, exudates digested by proteolytic enzymes and resorbed. This leaves tissue in pre-injury state.
Describe organization.
Sometimes granulation tissue grows into an area covers exudates, necrotic tissue, thrombous, clost into a fibrous tissue
Why does fetal tissue not scar?
Low levels of TGF-beta
What is the key factor involved in wound healing? What does it do?
TGF beta--Transforming growth factor beta. Links inflammation and healing. It is chemotactic for fibroblasts an dmacrophages, blocks pasminogen, enhances angiogenesis, stimulates collagen.
What other CDK’s are important in wound healing?
Platelet derived (PDGF), epithelial (EGF), fibroblast growth factor (FGF) families and TNF-alpha, integrins,
What are some retardants of wound healing?
Nutritional deficiency, hypoxia, vit C def, low temp, ionizing radiation, mobility of tissue, infection, foreign material .
What are some complications of wound healing?
Deficient scar formation = dehiscence, extensive scar formation = fibrous adhesions, exhuberant granulation= proud flesh, keloid formation, hypertrophic scarring, malignant change!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!