-
Features of apoptosis
(irreversible injury)
- No inflammation
- ATP mediated
- Cell shrinkage, nuclear blebbing, karryorhxis, karolysis, pyknosis (basophilia)
- Ca+2 influx to mediates caspases
-
Features of intrinsic apoptosis
- During embryogenesis, atrophy, hormone-induced.
- Decreased Bcl-2 (anti-apoptotic) and increased bax gene
- Increases mitochondrial permeability which releases cytochrome c to activate cytosolic caspases
-
Extrinsic apoptosis
- Cytotoxic T cells (perforin and granzyme B)
- FasL with FasR (CD95) on cell that needs to die
-
Enzymatic degradation and protein denaturation of a cell. Apoptosis or necrosis
- Necrosis
- inflammatory
- Cell swelling (unlike apoptosis = cell shrinkage and blebbing)
-
Forms of irreversible injury
- Mitochondrial damage
- Lysosomal rupture
- PM damage
- (apoptosis features)
-
Reversible injury with oxygen
- cell swelling
- impaired ATP pump
- nuclear chromatin clumping
- fatty change
- decreased glycogen
- ribosomal detachment (decreased protein synth)
-
Area of hypoxia in the heart
Subendocardial tissue
-
Where do red infarcts occur?
- Lung
- liver
- intestine
- reperfusion injury (caused by membrane damage and free radicals)
-
Difference between septic and cardiogenic/hypovolemic shock
Septic: damage to blood vessels due to toxins, which decreases TPR, vasodilation causes increased CO
Cardiogenic: damage to the heart - TPR increases, as blood is sent to the heart to stay there. Low CO
-
Rolling step for neutrophils
- E and P selectins on endothelium
- Sialyl-Lewis on leukocyte
-
Binding of neutrophils
- Endothelium: ICAM1
- WBC: LFA-1 (integrin)
-
Diapedesis of neutrophils (travels between endothelium)
Endo and WBC: PECAM-1
enhanced by platelet-activating factor
-
Migration of neutrophils
C5a, LTB4, IL-8, kallikrenin
enhanced by platelet-activating factor
-
Pathologies of free radical injury
- 1. Retinopathy of prematurity
- 2. Bronchopulmonary dysplasia
- 3. CCl4 in liver (fatty necrosis)
- 4. acetaminophen
- 5. iron overload
- 6. reperfusion injury (after thrombolytic therapy)
-
Weird bugs that produce granulomas
- Bartonella hensale (cat scratch dz)
- Berryliosis
- Syphilis ( gummas in 3rd phase)
-
Decreases ESR (fibrinogen coating RBCs to aggregate them)
- Sickle cell (altered shape)
- Polycythemia (too many RBCs)
-
Fe poisoning causing cell death
acute and chronic sx?
- peroxidation of cell membrane lipids
- acute: GI bleeding
- chronic: anion gap metabolic acidosis, scarring causes GI obstruction
-
Amyloid in multiple myeloma
Bence Jones (AL)
-
Amyloid in secondary amyloidosis (chronic inflammatory conditions)
AA
-
Amyloid in Alzheimer's
B-amyloid from APP
-
Amyloid in dialysis
B2-microglobulin from MHC-I molecules
-
Amyloid in cardiac and DM-II
- cardiac: transthyretin
- DM: amylin
-
How can cells invade basement membrane?
Using metalloproteinases (collagenases + hydrolases)
-
Desmoplasia
fibrous tissue formation in response to neoplasm
-
Anaplasia
- Cells lacking differentiation, resembles primitive cells of same tissue
- undifferentiated maligant cancers, irreversible change
-
Benign and malignant blood vessel tumor
-
Loss of weight, muscle atrophy, and fatigue that occur in chronic dz due to what factors
- Cachexia
- TNF-a, IL-6, and IFN-gamma
-
Immunodeficieny states and autoimmune dz can give what cancer
Lymphomas
-
Radiation exposure assoc with what cancer
Papillary thyroid cancer
-
Genes abl, ret, and erb-B2 are what kind
- Tyrosine kinase
- Proto-oncogenes
-
Gene c-kit is what tumor and what gene product
- gastrointestinal stromal tumor
- cytokine receptor, proto-oncogene
-
BRCA1 and 2 are what kind of gene products
- DNA repair proteins
- tumor suppressor genes: need to lose both alleles to express dz.
-
Bombesin is a tumor marker for
- Neuroblastoma
- n-myc (proto-oncogene)
-
- Cancers:
- Papillary Ca of thyroid
- Serous cystadenoCa of ovary
- Meningioma (brain)
- Mesothelioma
-
Mets to the brain
Lung>breast
-
Mets to the liver
colon > stomach
-
Mets to the bone
Prostate (blastic) > breast (lytic) > lung (lytic)
-
Tumors associated with EPO (2nd polycythemia)
- Renal cell ca
- hepatocellular ca
- pheochromocytoma
-
Liver toxins and cancer
Aflatoxin
Arsenic
Vinyl chloride
CCl4
- HCC
- angiosarcoma
- angiosarcoma
- centrilobular necrosis, fatty change
-
Napthalene (aniline) dyes - cancer?
TCC of bladder
-
Carcinoma origin? Sarcoma origin?
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