Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
297 Cards in this Set
- Front
- Back
|
Define etiology
|
the cause of a disease
|
|
|
Define pathogenesis
|
the sequence in manifestation of an illness
|
|
|
What are morphologic changes?
|
size, shape and color, consistency changes
|
|
|
What are functional derangements and clinical manifestations?
|
signs and symptoms a patient presents with
|
|
|
What's the difference b/w focal and diffuse?
|
focal is well defined or a definitive space. diffuse is broad region, not well defined or spread out
|
|
|
What are changes a cell may undergo in response to stimulus (rx of the body to injury or stress):
|
Cellular adaptation
Reversible cell injury Irreversible cell injury (death) |
|
|
What are LABILE cells? Example?
|
A continuously renewing, REGENERATING cell population.
Ex: epithelial cells |
|
|
What are STABLE cells? Example?
|
A (potentially) expanding cell population. Don't regenerate unless forced into division
Ex: hepatocyte, any -blast like a fibroblast |
|
|
What are PERMANENT cells? Example?
|
A static (can't regrow) cell population.
ONLY 2 KINDS: CNS cells and cardiac myocytes **Extremely specialized cells are much less likely to adapt |
|
|
What are the 5 cell adaptations?
*specific to stimulus and degree of specialization of the cell itself |
1. Atrophy 2. Hypertrophy 3. Hyperplasia 4. Metaplasia 5. Dysplasia
|
|
|
What is atrophy?
|
An adaptation to diminished need or resources for a cell's activities.
|
|
|
What occurs with atrophy?
|
Shrinkage of a cell or organ due to the loss of organelles.
|
|
|
What does atrophy involve?
|
Changes in both production and destruction of cellular constituents. A cell's reversible restructuring of its activities to help its survival and adapt to diminished use.
|
|
|
What causes pathological atrophy? Example?
|
Diminished blood supply, inadequate nutrition, loss of innervation, abnormal endocrine stim. loss, decreased workload.
EXAMPLES: atherosclerosis, spinal lesion, gland removal |
|
|
What is hypertrophy?
|
An increase in cell SIZE and functional capacity due to an increase in production and number of organelles (high metabolic demands)
*Tissue gets larger because the cells themselves are getting larger |
|
|
Where would you expect to find physiological hypertrophy?
|
muscles
|
|
|
Where could you find pathological hypertrophy?
|
heart: myocardial hypertrophy due to valve damage or MI
throat: goiter - hyperactivity of endocrine gland hormone-secreting tumor = hyperactivity of endocrine gland |
|
|
What is hyperplasia?
|
Increase in size of an organ or tissue due to an increase in the NUMBER of cells. Increased functional and/or metabolic demands on the cell or compensatory proliferation.
|
|
|
Where would you find physiological hyperplasia?
|
Lactating breast from hormonal stim. and increase in RBCs at high altitude.
|
|
|
When could you find pathological hyperplasia?
|
endometriosis (progesterone/estrogen levels out of whack)
psoriasis (layers piling up) liver regeneration (due to surgery) |
|
|
What is metaplasia?
|
A change/substitution in which one TERMINALLY DIFFERENTIATED cell type is REPLACED by ANOTHER terminally differentiated cell type. Metaplasia is basically a substitution.
|
|
|
Why would you find metaplasia?
|
Persistent injury/irritation (smoker)
Commonly, glandular epithelium is replaced by squamous ep. Not restricted to squamous differentiation. |
|
|
What conditions could produce metaplasia?
|
Smoking/bronchus or bladder transitional ep. changes to squamous
Barret esophagus Myositis ossificans |
|
|
What is dysplasia?
|
A DISORDERED/DISORGANIZED growth and maturation of the cellular components of a tissue.
Loss of Uniformity & Architectural orientation. Response to injury which may reverse. |
|
|
What conditions may give rise to neoplasia?
|
hyperplasia, metaplasia, dysplasia
|
|
|
What are the 3 categories of cellular ACCUMULATIONS?
|
1. Normal cellular constituent
2. An abnormal substance 3. A pigment |
|
|
Why might substances accumulate in a cell/organ?
|
Up! Production & Deposition
Down... Transport & Metabolism |
|
|
Give 6 examples of intracellular accumulations.
|
1. Steatosis 2. Hydropic change 3. Pigments 4. Proteins 5. Glycogen 6. Cholesterol
|
|
|
What is STEATOSIS and what is the most common organ involved? Caused from?
|
-Accumulation of FATTY ACIDS/triglycerides w/in parenchymal cells.
-Commonly involved in the LIVER. -Causes: protein malnutrition, toxins (ALCOHOL #1), obesity, anoxia |
|
|
What occurs in a cell with ischemia?
|
Low oxygen - Low pH - High lactate - Low ATP
*Both hypoxia and ischemia cause the Na/ATPase pump to fail, allowing water to rush in (following Na+) and engorge with fluid |
|
|
What is hydropic change/cellular swelling?
|
An increase in water accumulation within parenchymal cells. Water accumulates in the cytoplasm and in the actual CYTOPLASMIC ORGANELLES.
|
|
|
What is the most common cause of cellular swelling?
|
Hypoxia (lack of Oxygen) & Ischemia (lack of blood flow) that causes: Loss of ATP, due to fail of Na+/ATPase pump
|
|
|
Hemosiderosis
|
PIGMENT accumulation of IRON w/in parenchymal cells and w/in interstitium; golden brown granules
RBC's are degraded, pop, and form a bruise |
|
|
What is FOCAL hemosiderosis?
|
a common bruise (localized)
|
|
|
What is SYSTEMIC hemosiderosis?
|
Body looks bruised, can be from blood transfusions, hemolytic anemias, hemochromatosis (increased absorption of iron)
|
|
|
What is lipofuscin?
|
PIGMENT an undigestable mixture of lipids and proteins thought to be result of OXIDATIVE stress. WEAR AND TEAR (yellowish), increases with age
*Tends to be in the CNS |
|
|
What diseases could lead to glycogen accumulation?
|
Enzyme deficiency diseases.
|
|
|
What are the 4 enzyme deficiency diseases and what enzymes are they associated with?
|
1. Pompe: acid alpha glucosidase
2. McArdle: myophosphorylase 3. Cori: glycogen debranching enzyme 4. von Gierke: glucose-6-phosphatase |
|
|
Where can cholesterol accumulate?
|
Macrophages and vascular smooth muscle cells w/in blood vessel walls = ATHEROSCLEROSIS!
|
|
|
What is a disorder of cholesterol accumulation?
|
Xanthomas
*can affect skin, bone, joints, not just vascular |
|
|
7 causes of cell injury
HC IN PIG |
Hypoxia
Physical agent Chemical agent and drugs Infectious agent Immunological rx Genetic defects Nutritional imbalance |
|
|
What are SUB-cellular changes in REVERSIBLY injured cells? (2)
|
1. cellular swelling -crash of Na/ATPase pump = ion
2. steatosis -(fatty change) altered metabolism/transport of triglycerides *both of these injuries may become irreversible |
|
|
What are STRUCTURAL cell changes in REVERSIBLE injuries? (6)
|
Plasma membrane bleb - frothy, bubbly
Increased intracellular volume Mitochondrial swelling and calcification Dilated, vesicular ER Aggregated cytoskeletal elements vs. Disaggregated ribosomes |
|
|
What occurs in an IRREVERSIBLE injury of a cell? (3)
|
1. Vacuolization of the mitochondria - fuses to lysosome and E crash
2. Rupture of lysosomes - cell dies in its own digestive juices 3. Nuclear changes - pyknosis (small, shrunken & dark), karryorrhexis (fragmented), karyolysis (faded) |
|
|
What are the IRREVERSIBLE INJURY 3 nuclear changes and how do they present on a slide?
|
1. pyknosis: pinpoint nucleus (shrunken, small, dark)
2. karryorrhexis: fragmented nucleus - chopped up 3. karyolysis: nucleus no longer visible |
|
|
Review free radicals and the reactions in the body.
|
pgs. 27 - 31
|
|
|
What is dystrophic calcification?
|
Calcium deposition in dead (necrotic)/non-viable tissue
*BONDO! deposition of Ca+ salts - will not go away |
|
|
What is metastatic calcification?
|
Calcium deposition in NORMAL tissues due to hypercalcemia. (over entire area)
|
|
|
What is necrosis?
|
A spectrum of morphologic changes that occur in cells following cell DEATH IN LIVING TISSUE.
|
|
|
Necrosis is the sum of what two processes that follow cell death in living tissue or organs?
|
1. DENATURING of proteins
2. enzymatic digestion of organelles AUTOLYSIS |
|
|
What is coagulative necrosis?
|
Morphologic pattern of necrosis characterized by preservation of cellular outline, lacking nuclei
|
|
|
Where would coagulative necrosis occur?
|
heart, kidney tubular cells
|
|
|
What is liquefactive necrosis?
|
Morphologic pattern of necrosis characterized by destruction of the tissue, cellular debris, loss of architecture.
|
|
|
Where does liquefactive necrosis occur?
|
CNS
|
|
|
What is gangrenous necrosis?
|
Morphologic pattern of necrosis characterized by blue/black discoloration of the anatomy, visible with eyes.
|
|
|
When does gangrenous necrosis occur and what are the 2 types?
|
In limbs after disruption of blood supply. Dry = w/o bacterial infection and Wet = w/ bacterial infection
|
|
|
What is caseous necrosis?
|
Morphologic pattern of necrosis characterized by cheesy like consistency, necrotic debris resembles cheese.
|
|
|
Why would caseous necrosis occur?
|
TB (mycobacterium in the lungs)
|
|
|
What is enzymatic fat necrosis?
|
Morphologic pattern of necrosis characterized by enzymatic degradation of fat/lipids
|
|
|
What is the word for turn to soap (fat react w/ minerals) giving a bubbly necrotic debris?
|
saponification
|
|
|
Where does enzymatic fat necrosis readily occur?
|
pancreas. pancreatitis gives severe, lancinating epigastric pain
|
|
|
What do HSP 60 and HSP 70 do?
|
Involved in protein folding and targeting to final destination. (CHAPERONINS provide escort services)
|
|
|
What does ubiquitin do?
|
TAGS bad proteins and hurries along their degredation
|
|
|
Define inflammation.
|
A complex reaction to injurious agents such as microbes and damaged, usually necrotic cells that consists of vascular responses, migration and activation of WBCs and systemic reactions.
|
|
|
Give the 4 major players in the inflammatory process.
|
1. WBCs (leukocytes)
2. Blood vessels (capillaries & post-cap's only) 3. CT cells (fibroblasts) 4. Extracellular Matrix (collagen = scar) |
|
|
What are major causes of inflammation?
|
physical, chemical, microbiological, immune responses; anything that can damage a cell can cause inflammation
|
|
|
What is an acute inflammatory response both clinically and histologically?
|
Clinically: ACUTE, fast
Histologically: NEUTROPHILS then macrophages later |
|
|
What is a chronic inflammatory response both clinically and histologically?
|
Clinically: slow, CHRONIC INFLAMMATION
Histologically: LYMPHOCYTES & MACROPHAGES, fibroblasts |
|
|
What are the cardinal signs of inflammation? (both languages)
|
heat (calor), swelling (tumor), redness (rubor), pain (dolor), loss of function (functio laesa)
|
|
|
What is an edema? 2 types of edema?
|
Accumulation of fluid w/in the extravascular compartment and interstitial tissues
Inflammatory (exudate) or non-inflammatory (transudate) |
|
|
What is an exudate? example?
|
high PROTEIN
INFLAMMATORY Higher specific gravity *sunburn, blister, mild injuries |
|
|
What is an effusion?
|
BODY CAVITY fluid between visceral & parietal layers
|
|
|
What is a transudate? example of how occurs?
|
NON inflammatory
LOW protein low specific gravity *hemodynamic cause - ie R side heart failure so leaking fluid causes a transudate/non-inflammatory edema |
|
|
What is a serous exudate/effusion?
|
LOW cell count
yellow/straw-like color (clear) |
|
|
serosanguinous inflammation
|
A serous exudate, or effusion, that contains RBCs and has a red tinge. Has a low cell count because it is a serous exudate.
|
|
|
What is a fibrinous exudate?
|
Large amounts of FIBRIN due to activation of COAGULATION system. When occurs on pleura or pericardium, called "fibrinous pleuritis" or "f. pericarditis". Mayonnaise consistency.
|
|
|
What is a purulent exudate and what conditions is it frequently associated with?
|
HIGH cell count
white PUS |
|
|
What is suppurative inflammation?
|
Pus (purulent exudate) + LIQUEFACTIVE NECROSIS. Very bad.
|
|
|
What is the sequence of events in inflammation?
|
1. transient vasoconstriction 2. vasodilation 3. margination 4. adhesion/pavementation 5. emigration/migration via chemotaxis 6. aggregation 7. phagocytosis
|
|
|
Why does transient vasoconstriction occur?
|
constriction THEN vasodilation (ie, why you don't bleed immediately after a cut and then it gushes) to prevent hemorrhaging out.
|
|
|
Vasodilation during inflammation does what?
|
Increases BLOOD FLOW and cells/substrates to damaged tissues. Vasodilation itself is not enough - need to increase PERMEABILITY! (3 types)
|
|
|
What is an immediate-transient response?
|
Endothelial cell contraction (tight junctions open)
|
|
|
What is an immediate-sustained response?
|
Endothelial cell damage DEATH (large efflux)
|
|
|
What is delayed-prolonged leakage?
|
apoptosis? Cell exposed to damaging stim and then apoptoses b/c too damaged causing leakiness to begin.
*example: tanning |
|
|
What is stasis?
|
Decreased velocity of bloodflow and the reason simple vasodilation isn't enough to mediate inflammation but has to be combined with vascular permeability!
|
|
|
What does margination in inflammation mean?
|
Movement of WBCs toward vascular wall.
|
|
|
What do selectins do in the adhesion/pavementation stage of inflammation?
|
Rolls and sticks WBCs along the side of the vessel wall.
|
|
|
What do integrins do in the adhesion/pavementation stage of inflammation?
|
Sticks the WBCs firmly to the vessel wall.
|
|
|
What do immunoglobulins do in the adhesion/pavementation stage of inflammation?
|
Causes WBCs to squeeze b/w endothelial cells (transmigration).
|
|
|
What is not produced in the deficiencies LAD type 1 and 2?
|
LAD type 1: no selectins so cells have trouble adhering to wall. Pt's often sick with bacterial infex.
LAD type 2: no integrins. More severe. Short stature, cognitive defects. |
|
|
What is chemotaxis?
|
Movement along a chemical gradient.
|
|
|
What occurs with phagocytosis?
|
Recognition and binding of WBCs via opsonization (coat bacterium) Engulfment via endocytosis Killing via free radicals, lysosomal enzymes and production of AA metabolites
|
|
|
What are the opsonins?
|
C3b, IgG
|
|
|
What are the 3 systems associated with chemical mediators?
|
1. Kinin system 2. Complement system 3. Clotting system
|
|
|
Kinin system cascade produces what? What are its effects and how is it activated?
|
Bradykinin Pain, vasodilation, increased vascular permeability. Activated by the coagulation system ->Hageman Factor
|
|
|
The complement system is a family of 20 proteins, what are the 4 most important and what do they do?
|
1. C3a: VD and increased VP 2. C5a: VD and increased VP, chemotaxis; activates AA metabolism 3. C3b: opsonin (coats targets) 4. C5b-C9: membrane attack complex
|
|
|
What are other activators of the complement system and what do they do? (3)
|
1. Classic pathway: antigen antibody complexes turn on C1 turns on complement system 2. Alternate pathway: Interaction with LPS turns on complement system 3. Mannose Binding pathway: Microbial surfaces can exhibit sugar to turn on system
|
|
|
Describe the Coagulation Cascade.
|
Prothrombin becomes thrombin. Thrombin + fibrinogen -> fibrin. Plasminogen + tPA -> plasmin. Fibrin + plasmin -> fibrin split products (review notes on pg. 56)
|
|
|
Name 2 vasoactive amines and what they do.
|
1. Histamine: Major inflammatory chemical throughout body. Secreted by many cells and derived from basophils. Serotonin: Amine in GI tract and brain, augments blood flow (review notes on pg. 58)
|
|
|
What are the 2 Arachidonic Acid pathways?
|
1. Lipoxygenase pathway (LOX) 2. Cyclooxygenase pathway (COX)
|
|
|
What type of products does the COX pathway produce? (3)
|
prostaglandins (PG) thromboxane (TX) Lipoxins (LX)
|
|
|
What type of products does the LOX pathway produce? (2)
|
Leukotrienes (LT) Lipoxins (LX)
|
|
|
What LOX product is the cell derived chemotactic agents for WBCs?
|
LTB4
|
|
|
What protein of the complement system is a plasma derived chemotactic agent?
|
C5a
|
|
|
Which cytokine is a cell derived chemotactic agent for neutrophils only?
|
IL-8
|
|
|
What condition do leukotrienes mimic and why?
|
asthma; increased vascular permeability and vasodilation, hypersensitivity to something inhaled, bronchus closes
|
|
|
PGE2 increases/is associated with?
|
pain
|
|
|
Prostacyclin inhibits what and which proastaglandin is a prostacyclin?
|
platelet aggregation; PGI2
|
|
|
What does thromboxane do?
|
vasoconstricts and increases platelet aggregation
|
|
|
What is singulair's action on the arachidonic acid metabolites?
|
blocks leukotrienes by inhibiting LOX pathway
|
|
|
What are some examples of COX inhibitors?
|
Vioxx, Celebrex, NSAIDs
|
|
|
What do steroids inhibit?
|
Phospholipase, both LOX and COX
|
|
|
COX-1 is generally found in? COX-2 mainly produces?
|
GI tract Inflammation and pain
|
|
|
PGE2 and PDG2 cause what biologically?
|
induce vasodilation, bronchodilation; inhibits inflammatory cell function
|
|
|
PGI2 causes what biological activity?
|
Induces vasodilation, bronchodilation; Inhibits inflammatory cell function
|
|
|
PGF2a does what biologically?
|
Induces vasodilation, bronchoconstriction
|
|
|
TXA2 does what biologically?
|
Induces vasoconstriction, bronchoconstriction; Enhances inflammatory cell functions (especially platelets)
|
|
|
LTB4 causes what biological activity?
|
Chemotactic for phagocytic cells; stimulates phagocytic cell adherence; enhances microvascular permeability
|
|
|
LTC4, LTD4, LTE4 all cause what biologically?
|
Induce smooth muscle contraction; constrict pulmonary airways; increase microvascular permeability
|
|
|
What do fish oils do to arachidonic acid metabolism?
|
Inhibits AA present
|
|
|
Cytokines are categorized as and do what action?
|
Interleukins; tell cell's to do work
|
|
|
What are the roles of cytokines in inflammation? (5)
|
1. Induce synthesis of endothelium adhesion molecules 2. Induce synthesis of NO 3. Induce aggregation of neutrophils 4. Induce systemic acute-phase reactions 5. Chemotactic for neutrophils (IL-8 mainly)
|
|
|
What stimulates cytokine secretion?
|
Endotoxins, immune complexes, physical injury and produced by lymphocytes and macrophages (released with indication of tissue damage)
|
|
|
What 2 interleukins are the dictators of inflammatory response/first 2 to cause release of inflammatory mediators?
|
Interleukin 1 (IL-1) and Tumor/Tissue Necrosis Factor (TNF)
|
|
|
IL-2 takes what actions while mediating inflammation?
|
Responsible for adaptive host response, activates WBCs, recruits to fight off infections/tumors
|
|
|
IL-6 does what when mediating inflammation?
|
Involved in systemic acute phase reaction (flu-like symptoms); induces fever, pain, loss of apetite, malaise
|
|
|
IL-8 takes what action while mediating inflammation?
|
Cell derived chemotactic agent; chemokine for neutrophils only
|
|
|
What does TNF do an inflammation mediator?
|
Causes cell death -> triggers apoptosis in surrounding area
|
|
|
IL-1 and TNF play a role in what condition?
|
arthritis
|
|
|
IL-6 is special in that it can do what?
|
Cross the BBB to reset temperature at the hypothalamus
|
|
|
NO is a _______-derived _________ factor.
|
endothelial; relaxing derived from arginine
|
|
|
NO is synthesized by what 2 cells?
|
endothlial cells and macrophages
|
|
|
In what 2 forms is NO found?
|
Constitutive and inducible (endothelial cells and macrophages can induce)
|
|
|
What 2 actions can NO have in mediating inflammation?
|
Vasodilator and cytotoxic as a free radical; it mediates vascular tone and degrades foreign material
|
|
|
Platelet activating factor is derived from and is what?
|
membrane phospholipids; very potent and versatile mediator
|
|
|
Platelet activating factor (PAF) is synthesized by? (3)
|
1. all inflammatory cells 2. endothelial cells 3. injured tissue
|
|
|
Platelet activating factor has what functions? (5)
|
1. increased permeability 2. vasodilation 3. platelet aggregation 4. increased AA metabolism 5. increased leukocyte adherence
|
|
|
Review cytokine production flow chart
|
pg. 63
|
|
|
If a macrophage is autocrine, what happens?
|
self stimulating effect - macrophage has IL-2 receptor-activated when IL-2 released
|
|
|
If a macrophage is paracrine, what happens?
|
One cell secretes substance that has an immediate effect in neighboring cells
|
|
|
If a macrophage is endocrine, what happens?
|
Substance secreted and travels distance away and causes an effect
|
|
|
Review WBCs, their actions, what they release, etc.
|
pgs. 64-66
|
|
|
What is natural immunity? (3)
|
1. inflammatory response 2. Doesn't require prior exposure to offending agent (antigen) 3. Is non-specific and lacks memory
|
|
|
What is "acquired immunity"? (3)
|
1. A specific response to a specific antigen 2. Requires a sensitizing exposure 3. Response is magnified by subsequent exposure
|
|
|
IgA antibodies are found where?
|
nose, breathing passages, digestive tract, ears, eyes and vagina
|
|
|
IgA protect what parts of the body?
|
Surfaces that are exposed to the outside from foreign organisms and substances
|
|
|
IgA is found where?
|
saliva and tears
|
|
|
IgG antibodies are found where?
|
All body fluids but mostly in the blood.
|
|
|
How is IgG different in its size and abundance?
|
smallest but most abundant in body
|
|
|
IgG antibodies known for fighting what?
|
Bacterial and viral infections
|
|
|
IgG is special in that it can do what?
|
Only antibody that can cross the placenta and confer immunity to the fetus.
|
|
|
IgM antibodies are special how and are found where?
|
largest type; blood and lymph fluid
|
|
|
IgM are produced when?
|
First antibody produced in response to an infection.
|
|
|
IgD are found where and in what amount?
|
Tissues that line the cavities inside the body; small amounts
|
|
|
IgD plays a role in what?
|
allergic reactions to some substances like milk, some medications and some poisons
|
|
|
IgE are found where?
|
lungs, skin, mucous membranes
|
|
|
IgE protect the body against what substances?
|
pollen, fungus, spores and animal dander
|
|
|
IgE antibody levels are high in what type of people?
|
Those with allergies
|
|
|
A type 1 hypersensitivity reaction is mediated by and is of what type?
|
IgE; immediate
|
|
|
What are some examples of a type 1 hypersensitivity reaction?
|
hay fever, seasonal allergies, B-cell reaction to foreign antigen, anaphylactic reaction
|
|
|
What happens to mast cells in a type 1 hypersensitivity reaction?
|
IgE antibodies bind mast cells, basophils, cross link IgE receptors causing degranulation
|
|
|
A type 1 hypersensitivity reaction leads to and releases?
|
vascular leakage, especailly venules; various mediators including histamine
|
|
|
What is the 3 step process that occurs in a type 1 hypersensitivity reaction?
|
1. initial exposure to antigen = increased IgE production 2. IgE binds to mast cells 3. Subsequent exposure to antigen = binding to IgE and degranulation of mast cells -> histamine, leukotrienes, eosinophil chemotactic factor
|
|
|
A type 2 hypersensitivity reaction involves what antibodies binding to what?
|
IgG and IgM bind to fixed (not soluble) target antigens cytotoxic
|
|
|
What does an antibody do in a type 2 hypersensitivity reaction?
|
Antibody binds to fixed antigen, attracts complement and Ig-Fc receptor bearing cells. IgG or IgM bind to "self" antigens and trigger complement activation and tissue damage
|
|
|
What type of antibodies are found in a type 3 hypersensitivity reaction?
|
A type 3 is an immune complex mediated response and IgG and IgM bind to circulating antigens forming immune complexes
|
|
|
A type 4 hypersensitivity reaction is what type of reaction and what is not produced?
|
T-cell-mediated or delayed-type reaction; antibody not produced
|
|
|
What elicits a type 4 reaction?
|
the antigen itself
|
|
|
Type 4 is considered a delayed hypersensitivity why?
|
Foreign antigens elicit cytokine release (Il-1, 6, 12) by T helper cells and cytokines cause macrophage and lymphocyte activation
|
|
|
How long does a type 4 reaction take to occur?
|
24-48 hours after exposure
|
|
|
What are the outcomes of acute inflammation?
|
Complete resolution Healing by fibrosis/organization Abscess formation Chronic inflammation
|
|
|
Define chronic inflammation
|
Inflammation of prolonged duration (weeks or months) in which active inflammation, tissue destruction and attempts at healing are all proceeding simultaneously
|
|
|
What could cause chronic inflammation to arise without a pre-existing acute inflammatory component?
|
Persistent microbial infection Prolonged exposure to exogenous or endogenous toxic agents Autoimmune diseases
|
|
|
How does a macrophage "adapt" to chronic inflammation?
|
Becomes flattened out -> epithelioid cell Many fuse to become a "multi-nucleated giant cell"
|
|
|
What is granulomatous inflammation and what occurs with it?
|
A distinctive pattern of chronic inflammation: the predominant cell is the activated macrophage which possesses a modified epithelial like appearance; multinucleated giant cells, lymphocytes, necrosis and fibroblasts
|
|
|
What is a granuloma?
|
A focal area of granulomatous inflammation consisting of a central zone of necrosis surrounded by microscopic aggregates of epithelioid cells, lymphocytes and fibroblasts.
|
|
|
What causes a granuloma?
|
General: immune reaction, chronic irritation, undigestable foreign material, unknown etiology. specific: TB, leprosy, syphillis, sarcoidosis, fungal infection, suture.
|
|
|
What type of reaction tends to be granulomatous?
|
4
|
|
|
What does the wound healing and repair process involve?
|
Total reconstruction (regeneration/resolution) Partial reconstruction Universal repair tissue = fibrous CT scar
|
|
|
What are the 4 components to wound healing and repair and what do they involve?
|
Angiogenesis: migration and proliferation of endothelial cells Migration and proliferation of fibroblasts Deposition of extracellular matrix Remodeling of CT
|
|
|
What is granulation tissue?
|
The hallmark tissue of early healing by fibrosis (scab)
|
|
|
What is granulation tissue made up of?
|
Proliferating small capillaries, proliferating fibroblasts/myofibroblasts, extracellular fluid, macrophages
|
|
|
What is the function of granulation tissue?
|
Fill in tissue gaps Remove dead cell debris Aid in wound contraction Form an early pre-scar
|
|
|
What are the 7 steps of healing by primary union/intention?
|
1. blood clot fills incisional space 2. Neutrophil infiltration 3. Epithelial continuity restored 4. Macrophage infiltration 5. Granulation tissue fills space 6. Progressive collagenization 7. Remodeling
|
|
|
What are the 4 steps of healing by secondary union/intention?
|
1.Large amounts of granulation tissue are required 2. Inflammatory reaction is more prolonged 3. More debris and inflammatory exudate 4. More pronounced scar formation -> More myofibroblasts
|
|
|
What local (4) and systemic (3) factors influence wound healing?
|
type, size and location, vascular supply, infection, movement; circulatory status, infection, malnutrition
|
|
|
What is proud flesh?
|
Excessive granulation tissue. i.e. tiny cut but huge scab
|
|
|
What is keloid formation?
|
Hypertrophic scar: excessive collagen deposition
|
|
|
What is wound dehiscence?
|
Mechanical stress/ mechanical failure of a wound
|
|
|
What is contracture?
|
Excessive wound contraction i.e. myofibroblasts do too good of a job and cause dimpling of the skin
|
|
|
pink cytoplasmic stain
|
eosinophilic
|
|
|
blue or violet nucleus stain
|
basophilic
|
|
|
glassy change; an accumulation of mucus-like protein. Looks like this type of cartilage but tinted red.
|
Hyaline
|
|
|
from external environment
vs. from internal environment |
exogenous
vs. endogenous |
|
|
sickness
vs. death |
morbidity
vs. mortality |
|
|
sick with more than one thing at a time
|
co-morbidity
|
|
|
The potential for a cell to regenerate depends on what kind of cell it is. Name the 3 types of cells:
|
1. Labile - continuously turn over & regenerate
2. Stable - regenerate if forced 3. Permanent - cannot regenerate; two kinds only: CNS & heart cells |
|
|
normal loss of endocrine stimulation results in ___________ atrophy. This is based on supply and demand.
|
physiological atrophy
*is based on supply and demand of endocrine |
|
|
when one terminally differentiated cell is replaced/substituted by another in response to a PERSISTENT NOXIOUS STIMULI, injury, irritation.
|
Metaplasia
|
|
|
Commonly, glandular epithelium in the bronchus and bladder is replaced by _________ epithelieum during metaplasia.
|
squamous
|
|
|
Metaplasia when muscle behaves like bone, soft tissue swelling becomes bone
|
Myositis ossificans
|
|
|
why is a Barret esophagus significant?
|
cell change from glandular to squamous epithelium due to gastric reflux = first pathological step towards cancer/carcinoma
|
|
|
a pre-neoplastic lesion that is necessary stage in multi-step evolution of cancer
|
Dysplasia
|
|
|
What does severe dysplasia indicate should be done?
|
aggressive preventative therapy
|
|
|
A person is discovered to have a dysplasia. What is the presentation and what should be done?
|
disordered growth and maturation of cells, loss of uniformity and architecture. Persistent injury response. Pre-neoplasm so should be aggressively treated.
|
|
|
what 2 cells states are not pre-neoplasms and therefore not considered pre-cancerous?
|
atrophy and hypertrophy
|
|
|
states considered pre-cancerous (pre-neoplastic) regarding cell changes?
|
-Dysplasia(disordered),-Hyperplasia (increase in size due to increase in Number), -Metaplasia (substitution of one terminally dif. cell for another)
|
|
|
dividing layer at base of CIN grading method application for "real-world" dysplasia (disordered) cell growth:
|
stratum basale
|
|
|
In reaction to injury or stress, cells will accumulate __________.
|
substances
(they become little hoarders during the apocalypse) |
|
|
3 categories of accumulations of material within a cell or organ during times of disaster (injury, stress, etc):
|
normal cell substance
abnormal cell substance a Pigment |
|
|
Describe the substances accumulated during a cell as a response to stress or injury:
|
Substances may gather transiently or permanently, may be harmless or toxic, may be located in the cytoplasm or in the nucleus
|
|
|
Reasons (features of intracellular accumulation) for extra stuff in cells?
|
Increased production demands, decreased metabolism, decreased deposition, decreased transport
-overworked, fat, less turnout, less demand for your product so backlog |
|
|
accumulation of fat/triglycerides in cells has a _____________ appearance on a slide (due to alcohol)
|
signet ring
*Steatosis is reversible~ |
|
|
In signet ring appearance of steatosis due to alcoholism or obesity, where is the nucleus banished?
|
Peripheralized! (marginalized, poor bastard)
|
|
|
Besides alcoholism, obesity, anoxia and lack of protein, STEATOSIS is caused by the acummulation of?
|
CCL4
|
|
|
qualities caused by ischemia
|
down O2 and pH and ATP
(no air, acidic, no energy) up Lactate (increase waste products) |
|
|
What are some comparative changes between steatosis and hydropic change in a cell?
|
Hydropic (cellular swelling) does not peripheralize the nuclei - they stay centered. This indicates it's water, not fat, filling up the cells. No signet ring appearance. Hydropic is often in muscles, not liver.
|
|
|
accumulation of iron within parenchymal cells and interstitium
|
Hemosiderin
|
|
|
Cholesterol can accumulate in muscles and smooth muscle cells within blood vessel walls - name this disorder?
|
athersclerosis!
|
|
|
What four universal biochemical processes govern the manner in which cell injury manifests, regardless of its cause (HC IN PIG causes)?
|
Lack of Oxygen
Increases in intracellular Ca+ Depletion of ATP Defects in membrane permeability |
|
|
Universal biochemical process of Lack of Oxygen (or oxygen excess):
*Hypoxia or Anoxia |
decreases synthesis of ATP
|
|
|
Universal biochemical process of
Increases in intracellular Ca+: |
loss of Ca+ homeostasis = activates Ca+ dependent enzymes. If the cell can't regulate Ca+ for action potentials, then it commits suicide.
|
|
|
Universal biochemical process of
Depletion of ATP: |
loss of membrane fcn and intracellular processes (which leads to the 4th universal biochem process of defect in membrane permeability)
|
|
|
Universal biochemical process of
Defects in membrane permeability: |
necrosis or apoptosis results
|
|
|
What happens to cause cellular swelling in reversibly injured cells?
|
loss of Na/K/ATPase pump so sodium rushes in and water follows it
|
|
|
What has occurred when steatosis (fatty change) has built up in a reversibly injured cell?
|
the transport and/or metabolism of fatty acids has been changed somehow inside the cell
|
|
|
How to tell if cell has suffered irreversible rupture of lysosomes after heart attack?
|
Lactate dehydrogenase & Creatine kinase will be present in blood. Should only be present in muscles. After heart attack, these are in blood.
|
|
|
How to tell if cell has suffered irreversible rupture of lysosomes due to acute pancreatitis?
|
blood test - digestive enzymes like serum amylase and pancreatic amylase will appear in blood
|
|
|
karryorrhexis
|
fragmented, chopped up = dead cell
|
|
|
pyknosis
|
pinpoint and small
shrunken and dark |
|
|
karyolysis
|
faded, no longer visible
|
|
|
It is important to note the __________ in which a cell has become irreversibly injured
|
point of no return
|
|
|
What are the 3 "points of no return" for an HYPOXIC/ISCHEMIC cell injury from notes?
|
1. Severe mitochondrial vacuolization
2. lysosomal membrane rupture/ Activation of Ca+ dependent enzymes 3. Plasma membrane defects |
|
|
Describe Hypoxia/Ischemia situation in a cell that is reversible:
|
Down ATP & pH
Up Lactate (plan B for anerobic resp) Hydropic & Mitochondrial swelling Ribos pop off the RER |
|
|
4 Irreversible hypoxic/ischemia cell points of no return as explained by Dr. Arar?
|
1. Lysosomal membranes pop & cell autodigests
2. Plasma membrane pops & cell disintegrates into environment 3. Inability to sequester Ca+ turns on all of the autolysing 4. Mitochondria fuse with lysosome - vacuolization |
|
|
What is a free radical?
|
Molecule with an unpaired -e.
Produced as a normal intermediate in covalent chemistry. Made in lysosomes & peroxisomes. Immune system depends on -e to kill |
|
|
Free radicals are not normal when they occur in the cytoplasm, because the can damage you and cause disease. How do they damage?
|
Wants that octet stability & will rip an electron off a cell membrane, destroying a protein, degrading cell activity or damaging DNA.
|
|
|
Why do free radicals exist?
|
They are present between the shuttling of -e between chemical moieties, and are the final common pathway of many cell processes
|
|
|
Consist of a chemical species which are highly reactive, autocatalytic, and unstable
|
free radicals (-e)
|
|
|
Damage caused by free radicals when they aren't killing bacteria
|
Lipid peroxidation of cell membranes
Oxidative changes to cell processes Damage to DNA |
|
|
Free Radical producing pathway and uninstaller (deactivator):
|
(-e): O2 via NADPH & Xanthine oxidase --O2negative Superoxide anion --Superoxide dismutase --H2O2 -- Catalase (deactivates H+peroxide) --H2O & O2 inerts
|
|
|
a molecule like Vitamin E that sacrifices itself to a free radical is the product of what process?
|
Glutathione shunt
*too much Vit E or C (martyrs) due to oversupplementation will make them free radicals |
|
|
Fenton Reaction
|
Iron + Hydrogen peroxide = -OH free radical. This happens when we overconsume Fe+. Free rads go to liver, make hepatic carcinoma or cirrhosis.
|
|
|
Haber-Weiss Reaction
|
superoxide anion reaction with H+ to produce Hydrogen Peroxide and maintain free radical state
|
|
|
forms free radicals via Fe+-catalyzed Fenton reaction. Diffuses widely within the cell
|
Hydrogen Peroxide (H2O2)
|
|
|
Generated by LEAKS in the -e transport chain & cytosolic rx (xanthine oxidase). Produces other ROS. Likes to stay close to home.
|
Superoxide anion (O2-)
*likes to stay close to home |
|
|
Generated from H2O2 by Fe+-catalyzed Fenton rx. Intracellular radical most responsible for ATTACK on mAcromolecules.
|
Hydroxyl radical (*OH)
|
|
|
Formed from the reaction of nitric oxide (NO) with O2- and damages macromolecules
|
Just say NO to ONOO*! Peroxynitrite
|
|
|
Organic radical produced during lipid peroxidation
|
Lipid peroxide radicals (RCOO*)
|
|
|
Produced by macrophages and neutrophils during respiratory burst that accompanies phagocytosis. Dissociates to yield hypocholorite radical (OCL*)
|
Hypocholorus acid (HOCl)
|
|
|
Fe2+ ?
|
Ferrous iron
|
|
|
What minimize the effects of free radical damage but, like everything that is good for you, if overconsumed could increase free radical products?
|
Antioxidants
|
|
|
Overuse of O2 therapy can cause free radicals due to?
|
excess O2
*as in oxygen bars |
|
|
PMN's and macrophages can cause free radicals due to?
|
Inflammation
|
|
|
PMN's and xanthine oxidase can cause free radicals due to?
|
Re-perfusion injury after ischemia (ie, the blood returning)
|
|
|
Mixed function oxidation, cyclic redox reactions create free radicals when there is ?
|
chemical toxicity = redox
|
|
|
Radiotherapy creates free radicals when there is
|
ionizing radiation = radiotherapy
|
|
|
Mutagens create free radicals when there is
|
chemical carcinogenesis = mutagens
|
|
|
Mitochondrial metabolism creates free radicals when natural biological ________ occurs.
|
aging = mitochondria
|
|
|
When O2-, H2O2 or *OH are created, they are known as _____________________ and do membrane damage as free radicals.
|
activated oxygen
*very busy oxygen |
|
|
why won't dystrophic calcification go away over time?
|
Because it has NO characteristics of actual bone - no cortex, no traebeculae and most importantly, no osteoclasts to break it down.
|
|
|
example of dystrophic calcification in vessels
|
secondary as a result of atherosclerosis - dystrophic calcifications (Ca+ deposition) at aortic valves and arterial wall. Non-uniform.
|
|
|
example of dystrophic calcification in tendon
|
In tendo calcaneus (Achilles tendon) or supraspinatus tendon...small calcific densities in a tendon or ligament that won't go away b/c they aren't real bone. MYOSITIS OSSIFICANS
|
|
|
Metastatic calcification is Ca+ over a wide area. Example of something that would cause this widespread deposition of Ca+ all over the body?
|
Parathyroid-secreting tumors
*due to hypercalcemia |
|
|
Necrosis occurs only in ?
|
living organisms
|
|
|
necrosis vs. apoptosis
|
necrosis - death due to injury (irrev.)
VERSUS apoptosis -planned cell suicide (not pathological in nature) |
|
|
review necrosis slides
|
pp. 35-37 or lab manual
|
|
|
Where does enzymatic fat necrosis usually present as saponification and what color does it stain
|
Pancreas, because highly innundated with fatty acids and digested itself. Ca+ salts stain purple (saponification is usually extremely purple stain)
|
|
|
How are necrosis and apoptosis different?
|
Necrosis is murder and apoptosis is suicide
Necrosis is pathological (whoops!), but apoptosis is physiological (programmed) |
|
|
A labile cell that won't apoptose is usually ?
|
cancerous
|
|
|
3 basic causes of apoptosis
|
embryogenesis
hormone-dependent involution (adults) cell turnover in normally labile (skin) |
|
|
Inflammation follows ________, not __________.
|
necrosis = inflammation
not apoptosis |
|
|
brief description of apoptosis
|
cell shrinks
chromatin condenses apoptic bodies (blebbing off bits) phagocytosis of blebs by phagocytes |
|
|
Apoptosis is naturally culling the herd. It looks different than necrosis, although it may play a role in the pathogenesis of ___________.
|
neoplasms
|
|
|
Proteins which protect against thermal excess.
|
Heat Shock Proteins (HSP)
|
|
|
Are heat shock proteins always being made or only made in times of stress/injury?
|
yes.
"induced & constitutively synthesized" |
|
|
HSP's are induced during what 2 major events?
|
myocardial infarction MI
cerebral ischemia |
|
|
the healing process which attempts to repair damaged tissue
|
INFLAMMATION
|
|
|
describe some attributes of inflammation
|
Complex reaction in vascular CT
Accumulated fluid & leukocytes in extravascular tissue. Repair. Reconstitution. |
|
|
Cell regeneration, Scars, or both
|
Inflammation repair process
|
|
|
WBC's are also called ___________ (inflammation major player)
|
leukocytes
|
|
|
Are in intimate contact with tissue so exchange between themselves and the surrounding tissue during inflammation.
|
Capillaries and Post-capillary Venules only
|
|
|
Secrete extracellular matrix and collagen to form scar tissue during inflammation
|
Fibroblasts!
|
|
|
Deposited by fibroblasts as a precursor to scarring (inflammation major player)
|
Extracellular Matrix
|
|
|
After necrosis is inflammation. What happens after apoptosis?
|
nothing.
|
|
|
pattern of inflammation that produces a scar
|
CHRONIC
|
|
|
Chemical mediators are derived from ___ or cells.
|
plasma
*technically from liver cells but called plasma to differentiate |
|
|
type of cells found in acute inflammation and that completely reconstitute the tissue
|
neutrophils
|
|
|
type of cells found in chronic inflammation of unrecognizable tissue (destruction)
|
lymphocytes and macrophages w/ fibroblasts (scarring)
*tissue destroyed completely |
|
|
Three major components comprising the inflammatory response:
|
-vessel wall permeability changes
-vasodilation -leukocyte movement=EXTRAVASATION |
|
|
T V M Ad/pave E=mc to AGG + PHAGS on the street.
Inflammatory! Choreographed! *7 stages of inflammatory cascade |
In a highly choreographed, inflammatory series of events, Two Vain Men Adhered to the pavement, then Emigrated (via citytaxis) to Aggravate Phags on the street.
|
|
|
3 types of vascular permeability possible in the Vasodilation step #2 of choreographed inflammatory response:
|
Immediate-transient: endothelial
Immediate-sustained: endo cell killed Delayed-prolonged leakage: apoptos |
|
|
What is the problem with simple vasodilation as a means to handle inflammation?
|
it's too slow - gets more blood to tissue but STASIS increases viscosity. Must combine vasodilatoin with an increase in VASCULAR PERMEABILITY!
|
|
|
diapedesis
|
passage of blood or any of its formed elements through the intact walls of blood vessels
|
|
|
During what phase do WBC's begin to express adhesion molecules and why?
|
Margination
because they can't do anything from the center of the vessel. Adhesions are like sticky pads to catch hold for an exit to injury site. |
|
|
L.A.D. regarding genetic defects in adhesion molecules on WBC's
|
Leukocyte Adhesion Deficiencies
(of selectins, integrins, or immunoglobulins) |
|
|
How do LAD type 1 (no selectins) and LAD type 2 (no integrins) deficiencies illustrate importance of adhesions?
|
Damage cannot be easily fixed without adhesions so inflammatory healing process cannot occur
|
