PATHOLOGY Flashcards
Reversible cell injury
- Decrease ATP –> decrease activity of Ca2+ and Na+/K+ pumps –> cellular swelling (earliest morphologic manifestation), mitochondrial swelling
- Ribosomal/polysomal detachment –> decrease protein synthesis
- Plasma membrane changes (eg, blebbing)
- Nuclear changes (eg, chromatin clumping)
- Rapid loss of function (eg, myocardial cells are noncontractile after 1-2 minutes of ischemia)
- Myelin figures (aggregation of peroxidized lipids)
Irreversible cell injury
- Breakdown of plasma membrane –> cytosolic enzymes (eg, troponin) leak outside of cell, influx of Ca2+ –> activation of degradative enzymes
- Mitochondrial damage/dysfunction –> loss of electron transport chain –> decrease ATP
- Rupture of lysosomes –> autolysis
- Nuclear degradation –> pyknosis (nuclear condensation) –> karyorrhexis (nuclear fragmentation caused by endonuclease-mediated cleavage) –> karyolysis (nuclear dissolution)
- Amorphous densities/inclusions in mitochondria
Red (hemorrhagic) Infarct
- Occurs in venous occlusion and tissues with multiple blood supplies (eg, liver, lungs, intestine, testes), and with reperfusion (eg, after angioplasty).
- Reperfusion injury is due to damage by free radicals.
Pale (anemic) Infarct
Occurs in solid organs with a single (end- arterial) blood supply (eg, heart, kidney, spleen).
TGF-β
Angiogenesis
Fibrosis
FGF
Stimulates angiogenesis
VEGF
Stimulates angiogenesis
PDGF
- Secreted by activated platelets and macrophages
- Induces vascular remodeling and smooth muscle cell migration
- Stimulates fibroblast growth for collagen synthesis
Metalloproteinases
Tissue remodeling
EGF
Stimulates cell growth via tyrosine kinases (eg, EGFR/ErbB1)
Brain Metastases Primary Tumor
Lung > breast > melanoma, colon, kidney
Lots of Brain Metastases Can Kill
Bone Metastases Primary Tumor
Prostate, breast > kidney, thyroid, lung
Painful Bones Kill The Lungs
Liver Metastases Primary Tumor
Colon >> stomach > pancreas
Cancer Sometimes Penetrates liver
Mention Oncogenes
ALK
BCR-ABL
BCL-2
BRAF
c-KIT
c-MYC
CDK4
CCND1
ERBB1
HER2/neu (c-erbB2)
JAK2
KRAS
MYCL1 (L-myc-1)
N-myc (MYCN)
RET
Mention Tumor Suppressors
APC
BRCA1/BRCA2
CDKN2A
DCC
SMAD4 (DPC4)
MEN1
NF1
NF2
PTEN
RB1
TP53
TSC1
TSC2
VHL
WT1
WT2
ALK
Oncogene (chromosome 2)
- Receptor tyrosine kinase
- Associated with lung adenocarcinoma
BCR-ABL
- Oncogene
- Non-receptor tyrosine kinase
- Associated with CML, ALL
BCL-2
- Oncogene (chromosome 18)
- Antiapoptotic molecule
- Associated with follicular lymphoma, diffuse large B cell lymphoma
BRAF
- Oncogene (chromosome 7q34)
- Serine/threonine kinase
- Associated with melanoma, non-Hodgkin lymphoma, papillary thyroid carcinoma, hairy cell leukemia
c-KIT
- Oncogene (chromosome 4q12)
- Cytokine receptor
- Associated with gastrointestinal stromal tumors, mastocytosis
c-MYC
Oncogene (chromosome 8) Transcription factor Associated with Burkitt lymphoma
CDK4
Oncogene (chromosome 12) Cyclin-dependent kinase Associated with liposarcoma, melanoma, glioblastoma multiforme
CCND1
Oncogene (chromosome 11) Cyclin D (regulatory protein of the cell cycle) Associated with mantle cell lymphoma
ERBB1
Oncogene (chromosome 7) Epidermal growth factor receptor (EGFR) Associated with non-small cell lung cancer



