Pathology
Terms
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- What is hydropic swelling?
-
acute sublethal reversible injury
can cause cell swelling, large pale cytoplasm, membrane blebbing, mito swelling, detachment of ribosomes from ER, ER swelling, nucleolar disaggregation - what is hypertrophy
- increase in cell size accompanied by augmented functional capacity
- what is metaplasia?
-
conversion of one cell type into another.
usualy fully reversible, but may have associated risk of neoplastic transformaiton - what is dysplasia
- alteration in size, shape and organization of cellular components of tissue
- what are some intracellular storage problems?
-
fat
glycogen
iron (liver)
lipofuscin (yellow stuff)
melanin
inherited lysosomal storage diseases - Name the types of necrosis
-
1) coagulative
2) liquefactive
3) enzymatic fat
4) caseous
5) fibrinoid - What is coagulative necrosis?
-
denaturation of proteins, nuclear dissolution with PRESERVATION of cell outline.
Characteristic of hypoxic cell death/ischemia - What is liquefactive necrosis?
-
cellular digestion to a liquid, viscous mass.
Characteristic of focal bacterial or fungal infections - What is fat necrosis?
- focal areas of fat destruction, frequently associated with release of activated pancreatic enzymes into pancreatic tissue during pancreatitis
- What is caseous necrosis?
-
Subset of coagulative necrosis
Associated with TB and granulomatous inflammation - What is fibrinous necrosis?
- alteration of injured BV with insudation and accumulation of blood proteins causing vessel wall to stain intensely with eosin.
- What are the stages histologically of coagulative necrosis?
-
1) cytoplasm and organelle swelling, blebbing, ribosome detachment (reversible injury)
2) rupture of membranse, organeles, nuclear pyknosis (irreversible)
3) more rupturing.... - What is the most important cause of coagulative necrosis?
- ischemia
- describe the histologiocal stages of apoptosis
-
1) condensation of chromatin; compaction of cytoplasm
2) shrinkage, blebbing, nuclear fragmentation
3) cell fragmentatin as membrane bound apoptotic bodies
4) phagocytosis of those bodies - What is karyorrhexis?
- fragmentation of nucleus
- What are the categories of etiology (mnemonic)
-
1) vascular
2) inflammatory
3) neoplastic
4) drug
5) infectious
6) congenital
7) allergic
8) trauma
9) endocrine - How does eosin stain?
- stains basic things pink/red
- How does hematoxylin stain/
- stains acidic (neg charged) (??) things blue.
- What is in a granulomain the lung?
-
activated Mphages
giant cells
caseous necrotic core - What is inflammation
-
The reaction of living tissue and its microcirculation to pathogenic insult
Generation of inflammatory mediators
movement of fluid and leukocytes from blood into extravascular tissue - What are the characteristics of accute inflammation?
-
Immediate reaction to tissue injury
Rapid onset
Innate immnunity
Neutrophils mainly
Hours--weeks
prominent VASCULAR response - What are the characteristics of chronic inflammation
-
Persistant rxn to tissue injury
slow response
CMI
mainly mononuclear cells: lymphocytes, plasma cells, monos
weeks--years
less prominennt vascular response - Causes of accute inflammation
-
microbial infection
tissue necrosis
physical agents
chemical irritants
immune-mediated hypersensitivity - causes of chronic inflammation
-
persistant tissue injury & acute inflammation
microorgs resistant to phagocytosis or intracellular killing
foreign bodies
autoimmune disorders
primary granulomatous diseases - What are some primary granulomatous diseases that can trigger chronic inflammation?
-
Crohn's disease
sarcoidosis - Name some chemotactic factors that are inflammatory mediators
-
c5a
ltb4
chemokines - Name some vasoactive mediators of inflammation
-
histamine
serotonin
bradykinin
anaphylatoxins
leukotrienes/PGs
PAF
NO
LEADS TO EDEMA!!! - Name some outcomes of inflammation
-
1) abscess: excessive tissue destruction
2) persistant inflammation-->chronic inflam w/fibrosis
3) resolution
4) fibrosis (scar) - What are the classic signs of acute inflammation
-
Calor
Dolor
Tumor
Rubor
and loss of function - What are the major manifestations of acute inflammation?
-
1) rapid vascular response wiht altered microvasculature (dilation, flow up)
2) increased vascular permeability with accumulation of fluid and plasma components
3) intravascular stimulation of platelets
4) interaction of chemical mediators
5) emigration of neutrophils (PMNs)
6) Phagocytosis, intracellular kiling - what is effusion
- excess fluid in body cavities
- What are the causes of increased vascular permeability in acute inflammation
-
1) contraction of vascular endothelial cells makes gaps (Fast, short lived)
2) direct injury to the vessel
3) leukocytes injure vesssel from insiide and get out - What are some plasma derived mediators of edema?
-
1) Hageman factor (triggers clotting system), triggers bradykinin production
2) Complement activation system (C3a, C5a) - What are some cell derived mediators of edema?
-
1) Histamine (mast cell degranulation)
2) platelets (serotonin)
3) inlfammatory cells (PAF, PG, Leukotrienes)
4) Endothelium (NO, PAF, PGs) - What is transudate?
- edema fluid with LOW protein content
- What is exudate?
- edema fluid with HIGH protein content
- What is serous exudate
-
hi protein
absence of prominent cellular componenets - what is fibrinous exudate?
- contains large amts of fibrin from activation of coag
- what is prurulent exudate?
- prominent cellular components, usually neutrophils
- What is suppurative inflammation?
-
Subset of purulent exudate
purulent + liquefactive necrosis (pus) - what does hageman factor activation cause?
-
(=factor XII)
kinin generation
clot formation
anaphylatoxin generation (via complement cascade)
fibrin degradation product formation (fibrinolyiss) - what does fibrinolysis do wrt vascular permeabilty/
- augments it
- how else does hageman factor increase vascular permeability/
-
activates complement cascade, which produces anaphylatoxins (c3a, c5a)
generates kinins (bradykinin) - name a comoplement cascade opsin
- c3b
- name complement cascade anaphylatoxins
- c3a, c5a
- name a complement cascade chemoattractant
- c5a
- what is the MAC
-
c5b - c9
lyses cell
started by c5b - which is the most important anaphylatoxin
- c3a
- what effects do anaphylatoxins have?
-
chemotaxis
smooth muscle contraction (broncho and vasoconstriction)
increased vascular permeability - Name some more cell derived vasoactive mediators
-
1) AA metabolites (PG, TX, LT)
2) PAF
3) platelets
4) mast cell, basophil: hist, leukotrienes
5) endothelial cells: prostacyclin - What are the 2 ways AA can be metabolized?
-
Cyclooxygenase path-->PG and thromboxanes
Lipoxygenase path-->leukotrienes - What is PAF? What does it do?
-
1) generated by activated inflammatory cells (neutros, masts), endo cells, injured cells
2) induces platelet aggregation
3) enhances platelet release of serotonin
4) increase vascular permeability
5) recruits leukocytes
6) vasodilator
7) enhances phagocytosis
8) stimulates synthesis of AA pathways - What are the platelet derived mediators?
-
1) serotonin (-->vasc perm up_
2) TxA2 (AA-->cyclooxygenasepath-->SM constriction
3) cationic proteins (vasc perm up)
4) histamine - what does PGI2 do?
-
anti aggregatory for platelets
inhibits PMN respons - What are mast celll and basophil derived mediators?
-
histamine
leukotrienes (sm contract, vasc perm up)
PAF
cytokines - what is haptotaxis?
- chemotaxis along a fixed, insolumble chemotactic gradient
- what chemotaxins are the initial neutrophil recruiters?
-
c5a
LTB4 - what are the 3 stages of leukocyte emigration? what are they mediated by/
-
1) rolling: selectins, addressins
2) adhesion; integrins, ICAM
3) transmigration: PCAM - what is in neutrophil granules?
-
phospholipase A2
myeloperoxidase
lysozyme - what is the major bacteriocidal agent?
-
HOCl
(hypochlorous acid) - Name all of the bacteriocidal compounds
-
superoxide anion (respiratory burst)
hydrogen peroxide (substrate for other ROS)
HOCl
OH radical: another potent bactericide - what are symptoms of a myeloperoxidase deficiency?
- no HOCl, recurrent fungal infections
- what is chronic granulomatous disease?
- no NADPH oxidase, so you get no H202, which is a substrate for the real potent bactericides
- what are some diseases caused by inflammatory cells damamging tissue by releasing enzymes and ROS??
-
emphysema
rheumatoid arthritis - hemostasis definition
- arrest of hemorrhage following vascular injury
- what are the 2 paths of the coagulation cascade
-
1) Intrinsic cascade. FXII contacts thrombogenic surface.
2) Extrinsic cascade: blood is exposed to extravascular (subendothelial) tissue factor (TF) - Coagulation, generally
- conversion of soluble plasma fibrinogen to insoluble fibrillar polymer fibrin, catalyzed by thrombin
- What is probably the most important factor in thrombus progression and stabilization?
- Thrombin production
- Steps to no in clotting cascade
-
1) TF combines with VII
2) TF:VIIa catalzyses X-->Xa and IX--IXa
3) These steps are inhibited by TFPI tho
4) Meanwhile, THROMBIN Activates XI to XIa.
5) Thrombin also activates V and VIII and XIII.
6) these precursors help the steps in 2 progress better
7) this all leads to more creation of thrombin from prothrombin
8) finally, thrombin converts fibrinogen to soluble fibrin, and then soluble fibrin converst to insoluble fibrin via activated XIIIa - Whaat is VWF
-
Von Willebrand factor
enhances platelet adhesion by binding both to platelet membrane and fibrinogen - What do activated platelets do?
-
1) release granule contents (ADP, TxA2) that recruits more platelets and promotes aggregation
2) other factors released promote clotting cascade and thrombus formation - What does endothelium do to regulate the thrombus?
- releases NO and PGI2 (prostacyclin), which INHIBIT platelet aggregation
- Descibe hemophilia A
-
1) inherited coagulopathy
2) MOST COMMON X-linked recessive inherited bleeding disorder
3) absent/low F XIII
4) spontaneous bleeding into joints, muscles, organs
5) dr. brinkhous worked on this - Describe hemophilia B
-
1) less common X-linked recessive bleeding disorder
2) clinically indistinguishable from type A
3) "Christmas disease" - Describe vWD
-
1) the MOST COMMON HEREDITARY BLEEDING DISORDER
2) AUTOSOMAL DOMINANT (cf hemophilias, X-linked recessive)
3) abnormal/deficient vWF
4) also associated with reduced F XIII levels, since vWF is a carrier for F XIII
5) excessive blood loss from superficial injuries, operative and post traumatic injuries - Incidence of acquired coagulopathies
- GREATER than thhat of the inherited coagulopathies (hemophilia, vWD)
- Vitamin K deficiency
-
1) decrease in a bunch of factors (II, VII, IX, X)
2) malapsorption in the gut of stuff - Liver disease and coagulopathy
-
1) can cause impaired vit K absorption, leading to vit K deficiency-type coagulopathy
2) thrombocytopenia due to hypersplenism
3) reduced synthesis of clotting factors, fibrinogen - Characteristics of DIC
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an acquired coagulopathy characterized by widespread thrombosis AND hemorrhage secondary to the consumption of all of the platelets and coag factors elsewhere.
Also widepsread ischemia due to thrombosis - General cauases of DIC
-
1) tissue injury
2) endothelial cell injury - what are the major factors predisposing to thrombosis?
-
1) changes in blood constituents
2) changes to internal surface of BV
3) changes in patterns of blood flow - what is the most common cause of death in western industrialized countries?
- arterial thrombosis, with the complication of embolization
- definition of embolism
- passage through arterial or venous system of ANY material capable of lodging in the lumen and occluding it
- Materials able to cause embolism
-
thrombus
air
amniotic fluid
fat
atheromatous debris
foreign objects
tumor - Where can arterial emboli cause infarct
-
(usually cardiac source, e.g. mural thrombi)
1) brain
2) intestine
3) lower extremeties
4) kidney
5) heart - Describe amniotic fluid embolism
-
1) uncommon but lethal childbirth complication
2) sudden dyspnea, hypertension, SCA
3) ebolization of fetal material/debris
4) associated with DIC and ARDS - what is fat embolism associated with
- bone fractures
- what causes the nasty rotted off fingers?
-
Buerger disease
(necrosis secondary to thrombosis) - what cells are responsible for organizing a thrombus? how?
-
Phagocytes: injest thrombotic material
Fibroblasts: replace it with fibrosis - name some signs of greater thrombus reorganization
- clefts form in the thrombus, line themselves with endothelial cells! meanwhile fewer nucleii are seen inside the thrombus.
- what things can happen to a thrombus after formation
-
1) can be lysed either by endogenous enzypmes or drugs
2) can be replaced by fibrous tissue/reorganized - how are venous thrombi distinuishable from just blood in the lumen
-
1) you see signs of repair and healing
2) you see mphages injesting RBCs
3) you see endothelial proliferation in the adjacent vein wall - why do you get hemorrhagic infacts in the lung
- not an end-artery system like spleen or kidney. There is another, o2 rich arterial blood supply to lung (bronchial arteries, cf pulmonary arteries). this shoots in blood distal to the thromboembolism into necrotic vessels...hemorrhage ensues
- what is the most frequent cause of AAA?
- atherosclerosis with medial destruction
- What are possible consequences of AAAs
-
1) they may give rise to emboli of atheroma or mural thrombus
2) they may rupture and cause massive/fatal hemorrhage - Simplified clot cascade steps
-
1) vascular/endothelial injury releases TF
2) TF combines with VII to make TF:VIIa, which activates IX and X
3) IX and XIIIa activates X
4) Xa and Va catalzye prothrombin-->thrombin
5) thrombin converts fibrinogen to fibrin - what is chronic inflammation characterized by?
- interetitial fibrosis and influx of mainy MONONUCLEAR leukocytes (lymphocytes, monocytes, macrophages)
- what things induce chronic inflammation
-
1) stimulus not readily degradable
2) stimulus is incide a cell
3) stimulus IS a cess
4) recurrent injury
5) inflammation is induced by a T lymphocyte mediated immune response (contact dermatitis) - What are the most important effecter cells of chronic inflammation?
- mononuclear phagocytes and lymphocytes
- how are monocytes/macrophages activated and recruited?
-
1) monocytopoeisis, trigered by CSFs
2) vascular transmigration and chemotaxis
3) activation, via gamma interferon, LPS, polynucleotides - how are lymphocytes activated and recruited/
-
1) immune activation via antigen recognition y T lymphocyte antigen recceptors, B lymphocte antigen receptors, or antibodies
2) activation involves ccytokines - whhat are cytokines? Who releases them
-
= major molecular mediators of chronic inflammation
released by
1) mononuclear phagocytes
2) lymphocytes
3) non leugocytes like endothelial cells, fibroblasts - what do activated macrophages release?
-
1) lytic enzymes
2) phlogogenic lipid metabolites
30 toxic oxygen metabolites
4) plasma mediators or their activators (complement proteins, etc) - Describe granulomatous inflammation
-
A special form of chronic inflammation characterized by granulloma formation.
Granuloma is a dense accumulation of predominantly mononuclear phogocytes, typically with many showing difenrentiation into "epithelioid cells" - what causes many of the systemic signs and symptoms of choonic inflammation?
- cytokines
- what is granulation tissue
- tissue characterized by small new blood vessels with plump endothelium and active fibroblasts laying down collagen.
- are b lymphocytes involved in chronic inflammation mediation?
- no
- what kind of things do the cytokines IL-1 and TNNF cause?
-
1) activation of leukocytes
2) CNS effects--fever, somnolence, anorexia
3) skeletal muscle proteolysis, bone resorption--myalgias
4) proliferation of tissue cells (proud flesh) - are multinucleated giant cells found in granulomas
- sometimes, not always
- what is success of repair dependent on?
-
severity of injury
proliferative capacity of injured cells
nature of the inflammatory response
other mitigating/aggravating circumstances. - stages of "organization" of a MI
-
1) coagulative necrosis with acute inflammation
2) chronic inflammation w/early granulation tissue
3) Late granulation tissue
4) Focal fibrosis (scar) - What is sarcoidosis? what can be involved
-
multisystemic disease of unknown etiology invovling noncaseating granulomatous infection in many organs, including:
skin
uveal tract
hilar/mediastinal nodes
bone marrow
spleen
liver
lungs - is there always a gross process evident in viral myocarditis?
- no
- what does granulation tissue eventually do
- remodels into dense fibrous tissue
- in addition to sarcoidosis, what can cause granulomatous inflammation/
- fungal infection
- what are the nodules in a cirrhotic liver made up of?
- regenerating hepatocytes
- what is a characteristic of keloid microoscopicallly?
- wide, pink, accellular bands of stained collagen. not normal skin/dermis componenets. Large, darkly staining fibroblasts
- what is the major pathological process in viral myocarditis
- chronic inflammation
- which cytokines are most important in directly causeing the systemic signs of chronic inflammatory disease/
- IL-1 and TNF
- is infiltration with mononuclear leukocytes characteristic of acute, chronic, neither, or both viral myocarditis?
- BOTH
- hyperplasia, def
-
increase in cell number
usually associated with increase in tissue mass
can be physiologic or pathologic - metaplasia, def
-
change of one differentiated cell type into another.
USUALLY REVERSIBLE!!! - Dysplasia, def
-
1) abnormal appearing cells
pleomorphism
nuclear enlargment/irregularity
hyperchromatism
2) disorderly arranged cells
loss of polarity
loss of maturation
abnormal location of mitotic figures - Neoplasia, def
-
abnormal growth of tissue
excessive growth
uncoordinated and autonomous - histology of benign neoplasms
-
resemble normal tissue
histologically well differentiated
low mitotic rate
generally well circumscribed
does not metastasize - osteoma is...
- benign bone neoplasm
- chondroma
- benign Cartilage neoplasm
- Adenoma
- benign neoplasm of gland
- what are sarcomas?
- tumors that arise in CT like bone, muscle, fat
- where do carcinomas arise
- epithelium
- what group are sarcomas more common in?
- kids/teens
- is dysplasia reversible?
- yes
- what is grading
- a HISTOLOGICAL determination of how differentiated tumor cells are compared to the tissue they came from
- what are the 3 parts of a cancer staging
-
tumor (0-4)
nodes (0-4)
metastasis (0, +) - what is anaplasia
- very poorly differentiated neoplasm
- Rhabdo-
- skeletal muscle-derived
- leimyo-
- smooth muscle derived
- is leiomyoma at risk to turn into leiosarcoma?
- no
- how does tumor get from gut to liver
- hematogenous spread
- what is desmoplasia
- scarring response to tumor
- what is chronic myelogenous leukemia
-
cancer of white blood cells
bcr-abl tranlocation
targeted by magic bullet gleevec