Path Flashcards
Karyorrhexis
Nuclear fragmentation
Pyknosis
Nuclear shrinkage
Role of Apaf-1
Apaf-1 induces caspases, but Bcl-2 prevents cytochrome c release by binding and inhibiting Apaf-1
Role of FADD
After Fas-FasL crosslink, multiple Fas molecules coalesce, forming a binding site for a death domain containing adaptor protein, FADD. FADD binds inactive caspaces, activating them
Karyolysis
Dissolution
30 year old female presents with fibrinoid necrosis reasoning?
Commonly seen in preeclampsia where very high BP can cause fibrinoid necrosis of the placenta
Areas suceptible to hypoxia/ischemia and infarction Brain Heart Kidney Liver Colon
ACA/MCA/PCA boundary areas
Subendocardium of LV
Straight segment of proximal tubule (medulla) and thick ascending limb (medulla)
Around the central vein (zone III)
Splenic flexure, rectum (watershed areas that receive dual blood supply from most distal branches of 2 arteries, which protects these areas from single-focal blockage). However, these areas are suceptible to ischemia from systemic hypoperfusion.
Likelihood of cell injury based on what 3 factors?
1) Type of stress
2) Severity
3) Type of cell affected
Final electron acceptor in ETC
O2
Areas suceptible to ischemia from systemic hypoperfusion (eg. cardiac arrest, shock)
ACA/MCA/PCA boundary areas, splenic flexure, rectum
Hypoic ischemic encephalopathy affects what two cells
Pyramidal cells of hippocampus and purkinje cells of cerebellum
Organ suceptibility to infarction after occlusion of feeding artery is ranked greatest to least as follows:
CNS>Myocardium>Kidney>Spleen>Liver
3 organs suceptible to hemorrhagic infarction
Lung, liver, intestine
3 organs suceptible to pale infarction
Spleen, heart, kidney
Chromatolysis in 3 steps
Axonal injury causes
1) cellular body swelling
2) movement of nuclei to periphery
3) dispersion of nissl substance to increase protein synthesis to help with regeneration of axon
Dystrophic calcification
Normocalcemic deposition of calcium into abnormal tissues secondary to necrosis/injury
Metastatic calcification
Hypercalcemic (secondary to disorder that increases calcium) deposition of tissues into normal tissue
3 common tissues of metastatic calcification?
Kidney, lung, gastric mucosa b/c these tissues lose acid quickly. Increase in pH favors deposition
Mechanism of cytoskeleton degradation?
Ubiquitin proteosome degradation by intermediate filaments of cytoskeleton are “tagged” with ubiquitin and destroyed by proteosomes
Two mechanisms by decrease in cell size
Ubiquitin proteosome degradation of cytokskeleton and autophagy of cellular components
Most dangerous free radical
*OH (hydroxyl free radical)
3 scenarios where you would see exudate
Lymphatic obstruction, malignancy, inflammation/infection
3 scenarios where you would see transudate
Increase Na+ absorption, Increased hydrostatic pressure (HF), decreased oncotic pressure (nephrotic syndrome, cirrhosis)
Granuloma formation
1) MHC Class II presenting macrophages present antigen to CD4+ t cells
2) Secrete IL-12 to differentiate CD4+t cells into Th1 cells
3) TH1 cells secrete interferon gamma to activate macrophages
4) Macrophages secrete TNF alpha to maintain/induce granuloma formation
5 categories with increased ESR
inflammation (temporal arteritis), anemia (except sickle cell), infection, cancer (multiple myeloma), pregnancy, autoimmune
5 categories with decreased ESR
Sickle cell anemia (altered shape), polycythemia (increase RBC dilute aggregation factors), HF, microcytosis, hypofibrinogenemia
Primary amyloidosis has deposition of what
Deposition of proteins from Ig Light chains
Secondary amyloidosis has deposition of what
Fibrils composes of serum amyloid a (acute phase reactant seen in inflammation)
Dialysis-related has deposition of what
Fibrils composed of B2 microglobulin
Heritable amyloidosis due to?
Transthyretin gene mutation
Age-related (senile) systemic amyloidosis
Deposition of normal (wild-type) transthyretin
Organ-specific: Precursor protein/peptide responsible for localized amyloidosis 1) Cardiac atria: 2) Thyroid gland 3) Pituitary gland 4) Pancreatic islets in DM2 5) Alzheimer disease
Amyloid deposition into single organ
1) ANP
2) Calcitonin
3) Prolactin
5) B-amyloid protein
4) IAPP (islet amyloid polypeptide)
Lipofucin caused by
Lipid peroxidation
Method cells use to invade basement membrane
Collagenases and hydrolases (metalloproteinases)
How is cell-cell contact lost in invasive carcinoma?
Inactivation of E-cadherin which promotes metastisis
Metalloproteinases degrade?
Component of ECM and basement membrane, composed primarily of laminin+collagens (work through tissue remodeling)
P-glycoprotein and role in cancer therapy
ATP dependent efflux pump protein that has a broad specificity for hydrophobic compoudnds and pumps out toxins, including chemotherapeutic agents (one mechanism of decreased repsonsiveness or resistance to chemotherapy over time)
Which has a more prognostic value? Stage or grade?
Stage
Anaplasia
Equated with undifferentiated malignant neoplasms with complete lack of differentiation and no resempblance to tissue of origin
Single most important prognostic factor for cancer prognosis?
Metastases
Desmoplasia
Fibrous tissue formation in response to neoplasm
Sarcoma origin
Mesenchymal
Carcinoma origin
Epithelial
Most Carcinomas spread via _____ while most sarcomas spread ______
lymphatics, hematogenously
Epithelium derived benign/malignant cancer
adenoma, papillary adenoma
Adenocarcinoma, papillary carcinoma
Mesenchyme (blood cells) beningn and malignant cancer
Beningn does not exist
Malignant Lukemia, lymphoma
Blood vessels benign and malignant cancer
Benign Hemangioma
Malignant: Hemangiosarcoma
Smooth muscle benign and malignant cancer
Benign: Leiomyoma
Malignant: Leiomyosarcoma
Striated muscle benign and malignant cancer
Benign: Rhabdomyoma
Malignant: Rhabdomyosarcoma
Connective tissue benign and malignant cancer
Benign: Fibroma
Malignant: Fibrosarcoma
Bone benign and malignant cancer
Benign: Osteoma
Malignant: osteosarcoma
Fat benign and malignant cancer
Benign: Lipoma
Malignant: Liposarcoma
What is cachexia mediated by
TNFalpha (cachectin)–>main mediator, IFN gamma, IL1, IL6