First Aid Pathology Flashcards
Apaptosis
programmed cell death
ATP required
no significant inflammation (unlike necrosis)
characterized by deeply eosinophilic cytoplasm, cell shrinkage, nuclear shrinkage (karyorrhexis), and formation of apoptotic bodies
Intrinsic pathway
involved in tissue remodeling in embryogenesis
occurs when a regulating factor is withdrawn from a proliferating cell population or after exposure to injurious stimuli
Extrinsic pathway
2 pathways:
- ligand receptor interactions (FasL binding to Fas)
- immune cell (cytotoxic T-cell release of perforin and granzyme B)
Necrosis
enzymatic degradation and protein denaturation of cell due to exogenous injury resulting in leakage of intracellular components inflammatory process (unlike apoptosis)
coagulative necrosis:
seen in
due to
histo
- ischemia/infarcts in most tissues (except brain)
- ischemia or infarction; proteins denature, then enzymatic degradation
- cell outline preserved; incr. cytoplasmic binding of acidophilic dyes
liquefactive necrosis:
seen in
due to
histo
- bacterial abscesses, brain infarcts (due to incr fat content)
- neutrophils releasing lysosomal enzymes that digest the tissue; enzymatic degradation first, then protein denatures
- early: cellular debris and macrophages; late: cystic spaces and cavitation (brain), neutrophils and cell debris seen with bact. infxn
caseous necrosis:
seen in
due to
histo
- TB, systemic fungi
- macrophages wall off infecting microbes (granular debris)
- fragmented cells and debris surrounded by lymphocytes and macrophages
fat necrosis
seen in
due to
histo
- enzymatic: acute pancreatitis; nonenzymatic: breats trauma
- damaged cells release lipase, which breaks down fatty acids in cell membranes
- outlines of dead fat cells without peripheral nuclei; saponification of fat (combined with Ca2+) appears dark blue on H&E stain
fibrinoid
seen in
due to
histo
- immune reactions in vessels
- immune complexes combine with fibrin (vessel wall damage)
- vessel walls are thick and pink
gangrenous
seen in
due to
histo
- distal extremity, after chronic ischemia
- dry: ischemia; wet: superinfection
- dry: coagulative (cell outline preserved); wet: liquefactive (early: cellular debris and macrophages; late: cystic spaces and cavitation)
cellular injury
reversible
ATP depletion cellular/mitochondrial swelling (decr. ATP, decr activity of Na+/K+ pump) nuclear chromatin clumping decr glycogen fatty change ribosomal/polysomal detachment membrane blebbing
cellular injury
irreversible
nuclear pyknosis (shrinkage), karyorrhexis (fragmentation), karyolysis
plasma membrane damage (degradation of membrane phospholipid)
lysosomal rupture
mitochondrial permeability/vacuolization; phospholipid-containing amorphous densities within mitochrondria (swelling alone is reversible)
Ischemia
susceptible areas:
organ and location
- brain (ACA/MCA/PCA boundary areas)
- heart (Subendocardium, LV)
- kidney (straight segment of proximal tubule (medulla), thick ascending limb (medulla)
- liver (area around central vein (zone III)
- colon (splenic flexure, rectum)
Infarcts
red
red = hemorrhagic infarcts occur in venous occlusion and tissues with multiple blood supplies, such such as liver, lung and intestine Reperfusion injury (after angioplasty) is due to damage by free radicals *think REd for REperfusion
Infarcts
pale
Pale = anemic infarcts
occur in solid organs with a single (end-arterial) blood supply, such as heart, kidney, and spleen
define atrophy
reduction in the size and/or number of cells
causes of atrophy
- decr endogenous hormones (eg post-menopausal ovaries)
- incr exogenous hormones (eg steroid use)
- decr innervation (eg motor neuron damage)
- decr blood flow/nutrients
- decr metabolic demand (eg paralysis)
- incr pressure (eg nephrolithiasis)
- occlusion of secretory ducts (eg calculus/stones)
five characteristics of inflammation
rubor (redness) dolor (pain) calor (heat) tumor (swelling) functio laesa (loos of function)
vascular component of inflammation
incr vascular permeability, vasodilation, endothelial injury
cellular component of inflammation
neutrophils extravasate from circulation to injured tissue to participate in inflammation through phagocytosis, degranulation, and inflammatory mediator release
acute cellular component of inflammation
neutrophil, eosinophil, and antibody mediated
acute inflammation is rapid onset (sec - min) and of short duration (min - days)
outcomes include complete resolution, abscess formation, or progression to chronic inflammation
chronic cellular component of inflammation
mononuclear cell and fibroblast mediated
characterized by persistent destruction and repair
assoc with blood vessel proliferation, fibrosis
granuloma: nodular collections of epitheliod macrophages and giant cells
outcomes include scarring and amyloidosis
what is chromatolysis?
process involving the neuronal cell body following axonal injury
changes reflect incr protein synthesis in effort to repair the damaged axon
characterized by:
round cellular swelling
displacement of the nucleus to the periphery
dispersion of Nissl substance throughout cytoplasm
define dystrophic calcification
Ca2+ deposition in ABNORMAL TISSUE, secondary to injury or necrosis
tends to be localized (eg calcific aortic stenosis)
seen in TB (lungs and pericardium), liquefactive necrosis of chronic abscesses, fat necrosis, infarcts, thrombi, schistosomiasis, Monchkeberg arteriolosclerosis, congenital CMV + toxoplasmosis, psammoma bodies
*is not directly assoc with serum Ca2+ levels (pt usually normocalcemic)
define metastatic calcification
widespread deposition of Ca2+ in NORMAL TISSUE secondary to hypercalcemia or high calcium-phosphate product levels
Ca2+ deposits predominantly in interstitial tissues of kidney, lung, and gastric mucosa (these tissues lose acid quickly, incr pH favors deposition)
*pt is usually not normocalcemic
Leukocyte extravasation
WBCs exit from blood vessels at sites of tissue injury and inflammation in 4 steps
1) margination and rolling (defective in leukocyte adhesion deficiency type 2), involves E-selectin, P-selectin, and GlyCAM-1, CD34
2) tight-binding (defective in leukocyte adhesion def. type 1), involves ICAM-1 (CD54)
3) diapedesis (WBC travels btwn endothelial cells and exits blood vessel), involves PECAM-1 (CD31)
4) migration (WBC travels through interstitium to site of injury or infection guided by chemotactic signals released in response to bacteria (C5a, IL-8, LTB4, kallikrein, platelet-activating factor)
what is free radical injury?
free radicals damage cells via membrane lipid peroxidation, protein modification, and DNA breakage
when are free radicals initiated?
radiation exposure, metabolism of drugs (phase I), redox reactions, nitric oxide, transition metals, WBC (neutrophils, macrophages) oxidative burst
how are free radicals eliminated?
- scavenging enzymes such as catalase, superoxide dismutase, glutathione peroxidase
- spontaneous decay
- antioxidants (Vit A, C, E)
- metal carrier proteins (transferrin, ceruloplasmin)
Pathologies that involve free radical injury
- retinopathy of prematurity
- bronchopulmonary dysplasia
- carbon tetrachloride, leading to liver necrosis (fatty change)
- acetaminophen overdose (fulminant hep, renal papillary necrosis)
- iron overload (hemochromatosis)
- reperfusion injury (superoxide), esp after thrombolytic therapy
what’s an inhalation injury?
pulmonary complication associated with smoke and fire
caused by heat, particulates (
sx of inhalation injury?
chemical tracheobronchitis edema pneumonia ARDS many pts present secondary to burns, CO inhalation, or arsenic poisoning
hypertrophic scars vs keloid scars in terms of collagen synthesis collage arrangement extent recurrence notes
hypertrophic: has moderate collagen synth collagen is parallel scar confined to borders of original wound infrequently recur following resection keloid: high levels of collagen synth collagen is disorganized scar extends beyond borders of original wound frequently recur following resection higher incidence in african americans
wound healing:
tissue mediators and their functions
PDGF- secreted by activated plalets and macrophages, induces vascular remodeling and smooth muscle cell migration, stimulates fibroblast growth for collagen synth
FGF- stimulates angiogenesis
EGF- stimulates cell growth via tyrosine kinases
TGF-beta- angiogenesis, fibrosis, cell cycle arrest
metalloproteinases- tissue remodeling
VEGF- stimulates angiogenesis
phases of wound healing
inflammatory (up to 3 days after wound)
mediators and characteristics
-platelets, neutrophils, macrophages
clot formation, incr vessel permeability and neutrophil -migration into tissue; macrophages clear debris 2 days later
phases of wound healing
proliferative (day 3- weeks after wound)
mediators and characteristics
- fibroblasts, myofibroblasts, endothelial cells, keratinocytes, macrophages
- deposition of granulation tissue and collagen, angiogenesis, epithelial cell proliferation, dissolution of clot, and wound contraction (mediated by myofibroblasts)
phases of wound healing
remodeling (1 week- 6+ mo after wound)
mediators and characteristics
- fibroblasts
- type III collagen replaced by type I collagen, incr tensile strength of tissue
Granulomatous disease
- Bartonella henslae (cat scratch disease)
- Berylliosis
- Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
- Crohn disease (noncaseating granuloma)
- Foreign bodies
- Francisella tularensis
- Fungal infections (caseous necrosis)
- Granulomatosis with polyangiitis (Wegener)
- Listeria monocytogenes (granulomatosis infantiseptica)
- M. leprae (leprosy; Hansen disease)
- M. tuberculosis (caseous necrosis)
- Treponema pallidum (tertiary syphilis)
- Sarcoidosis (noncaseating granuloma)
- Schistosomiasis
pathogenesis of granuloma formation
Th1 cells secrete IFN-gamma, activating macrophages
TNF-alpha from macrophages induces and maintain granuloma formation
what drugs can cause disseminated disease?
Anti-TNF drugs can, as a side effect, cause sequestering granulomas to break down, leading to disseminated disease
Always test for latent TB before starting anti-TNF therapy!
Exudate
think THICK cellular protein rich specific gravity > 1.020 Due to: lymphatic obstruction, inflammation/infxn, malignancy
Transudate
think THIN
hypocellular
protein-poor
specific gravity
what is ESR (erythrocyte sedimentation rate)?
products of inflammation (eg fibriongen) coat RBCs and cause aggregation
the denser the RBC aggregates fall at a faster rate within a pipette tube. Often co-tested with CRP levels
things that cause increased ESR?
most anemias infections inflammation (eg, temporal arteritis) cancer (eg, multiple myeloma) pregnancy AI disorders (eg SLE)
things that cause decreased ESR?
sickle cell anemia (altered shape) polycythemia (inc RBCs "dilute" aggregation factors) HF microcytosis hypofibrinogenemia
describe amyloidosis
abnormal aggregation of proteins (or their fragments) into beta-pleated sheets. leads to damage and apoptosis
types of amyloidosis:
AL (primary)
due to deposition of proteins from Ig Light chains
can occur as a plasma cell disorder or associated with multiple myeloma
often affects multiple organ systems: renal (nephrotic syndrome), cardiac (restrictive cardiomyopathy, arrhythmia), hematologic (easy bruising, splenomegaly), GI (hepatomegaly), and neurologic (neuropathy)
types of amyloidosis:
AA (secondary)
fibrils composed of serum Amyloid A
often multisystem
seen with chronic inflammatory conditions such as RA, IBD spondyloarthropathy, protracted infection
types of amyloidosis:
Dialysis-related
fibrils composed of beta2- microglobulin
seen in patients with ESRD and/or on long-term dialysis
may present in carpal tunnel syndrome
types of amyloidosis:
Heritable
heterogeneous group of disorders, including familial amyloid polyneuropathies due to transthyretin gene mutation
types of amyloidosis:
Age-related (senile) systemic
due to deposition of normal (wild-type) transthyretin in myocardium and other sites
slower progression of cardiac dysfunction relative to AL amyloidosis
types of amyloidosis:
Organ-specific
Amyloid deposition localized to a single organ
most important form is amyloidosis in Alzheimer disease due to deposition of beta-amyloid protein cleaved from amyloid precursor protein (APP)
Islet amyloid polypeptide (IAPP) is commonly seen in DM type 2 and is caused by deposition of amylin in pancreatic islets
What’s lipofuscin?
a yellow-brown “wear and tear” pigment associated with normal aging
how is lipofuscin made?
formed by oxidation and polymerization of autophagocytosed organellar membranes
hyperplasia
cells incr in number
dysplasia
abnormal proliferation of cells with loss of size, shape, and orientation
carcinoma in situe/preinvasive
neoplastic cells have not invaded intact basement membrane
incr nuclear/cytoplasmic (N/C) ratio and clumped chromatin
neoplastic cells encompass entire thickness
invasive carcinoma
cells have invaded basement membrane using collagenases and hydrolases (metalloproteinases)
cell-cell contacts lost by inactivation of E-cadherin
metastasis
spread to distant organ
“seed and soil” theory of METS
seed= tumor embolus
soil= target organ is often the first-encountered capillary bed
the cancer cells being the “seeds” and the specific organ microenvironments being the “soil.”
what’s P-glycoprotein?
AKA multidrug resistance protein 1 (MRP1)
classically seen in adrenal cell carcinoma but also expressed by other cancer cells
used to pump out toxins, including chemotherapeutic agents (one mechanism of decr responsiveness or resistance to chemotherapy over time)
carcinoma implies
epithelial origin
sarcoma implies
mesenchymal origin
carcinoma and sarcoma both imply
malignancy
most carcinomas spread via
lymphatics
most sarcomas spread via
blood
non-neoplastic malformation
hamartoma (disorganized overgrowth of tissue in their native location)
choristoma (normal tissue in a foreign location)
benign epithelial tumors
adenoma
papilloma
benign blood vessel tumor
hemangioma
benign smooth muscle tumor
leiomyoma
benign striated muscle tumor
rhabdomyoma
benign connective tissue tumor
fibroma
benign bone tumor
osteoma
benign fat tumor
lipoma
malignant epithelial tumor
adenocarcinoma
papillary carcinoma
malignant blood cell tumors
leukemia
lymphoma
malignant blood vessel tumor
angiosarcoma
malignant smooth muscle tumor
leiomyosarcoma
malignant striated muscle tumor
rhabdomyosarcoma
malignant connective tissue tumor
fibrosarcoma
malignant bone tumor
osteosarcoma
malignant fat tumor
liposarcoma
description of benign tumor
well differentiated well demarcated low mitotic activity no METS no necrosis
description of malignant tumor
poor differentiation erratic growth local invasion METS decr apoptosis upregulation of telomerase prevents chromosome shortening and cell death
description of cachexia
weight loss muscle atrophy fatigue occurs in chronic dz (CA, AIDS, HF, TB) mediated by TNF-alpha, IFN-gamma, IL-1, and IL-6
Oncogene
description
need damage to
gain of function -> incr CA risk
need damage to only 1 allele
Tumor suppressor
description
need damage to
loss of function -> incr CA risk
need damage to both alleles
what should tumor markers be used for? what shouldn’t they be used for?
- used to monitor tumor recurrence and response to tx
- shouldn’t be used as primary tool for CA dx or screening
what are psammoma bodies? what diseases are they associated with?
-laminated, concentric spherules with dystrophic calcification
PSaMMoma
P=papillary carcinoma of thyroid
S= serous papillary cystadenocarcinoma of ovary
M=meningioma
M=malignant mesothelioma
Cancer incidence in men
- prostate
- lung
- colon/rectum
Cancer incidence in women
- breast
- lung
- colon/rectum
Cancer mortality in men
- lung
- prostate
- colon/rectum
Cancer mortality in women
- lung
- breast
- colon/rectum
what’s the primary leading cause of death in US? 2nd?
- hear disease
- cancer
common METS to brain from tumors in:
lung > breast > prostate > melanoma > GI
common METS to liver from tumors in:
colon»_space; stomach > pancrease
common METS to bone from tumors in:
prostate/breast > lung/thyroid/kidney
