Programmed cell death; ATP required. Mediated by caspases.
Apoptosis is characterized by...?
Cell shrinkage, nuclear shrinkage and basophilia (pyknosis), membrane blebbing, pyknotic nuclear fragmentation (karyorrhexis), nuclear fading (karyolysis), and formation of apoptotic bodies, which are then phagocytosed. No significant inflammation.
When does apoptosis occur?
Occurs during embryogenesis, hormone induction (menstruation), immune cell-mediated death, injurious stimuli (e.g., radiation, hypoxia), atrophy (e.g., endometrial lining during menopause)
Enzymatic degradation of a cell resulting from exogenous injury.
Necrosis is characterized by...?
Enzymatic digestion and protein denaturation, with release of intracellular components. Inflammatory.
Restoration of normal structure. Granulation tissue -- highly vascularized, fibrotic. Abscess -- fibrosis surrounding pus. Fistula -- abnormal communication. Scarring -- collagen deposition resulting in altered structure and fxn.
Characteristics of trans udate
Hypocellular Protein-poor Specific gravity > 1.012 Due to: Incr hydrostatic pressure Decr oncotic pressure Na+ retention
Characteristics of ex udate
Cellular Protein-rich Specific gravity < 1.020 Due to: Lymphatic obstruction Inflammation
Neutrophils exit from blood vessels at sites of injury and inflammation in 4 steps: 1.) Rolling 2.) Tight binding 3.) Diapedesis 4.) Migration <img src="218a.JPG" />
Rolling (step 1 in leukocyte extravasation)
Mediated by E-selectin and P-selectin on vascular endothelium binding to sialyl Lewis^x on the leukocyte. <img src="218a.JPG" />
Tight binding (step 2 of leukocyte extravasation)
Mediated by ICAM -1 on vascular endothelium binding to LFA-1 (integrin) on the leukocyte ("Hold on tight to your CAM era") <img src="218a.JPG" />
Diapedesis (step 3 in leukocyte extravasation)
Leukocyte travels btw endothelial cells and exits blood vessel; PECAM-1 is involved. <img src="218a.JPG" />
Migration (step 4 in leukocyte extravasation)
Leukocyte travels thru the interstitium to the site of injury or infxn guided by chemotactic signals (e.g., cytokines) <img src="218a.JPG" />
Things that initiate Free radical injury
Radiation exposure Metabolism of drugs (phase I) Redox rxtn Nitric oxide Transition metals Leukocyte oxidative burst *Reperfusion after anoxia induces free radical production (e.g., superoxide) and is a major cause of injury after thrombolytic therapy
Free radical injury induces cell injury thru...?
Membrane lipid peroxidation Protein modification DNA Breakage
Free radical degradation
Produced thru enzymes (catalase, superoxide dismutase, glutathioe peroxidase), spontaneous decay, antioxidants (Vitamins A, C, E).
Beta-pleated sheet demonstrable by apple-green birefringence of Congo red stain under polarized light; affected tissue has waxy appearance.
Type of amyloid protein: Primary Protein? Derived from...?
AL protein Derived from Ig L ight chains (multiple myeloma) (AL = L ight chains)
Type of amyloid protein: Secondary Protein? Derived from...?
AA protein Derived from serum amyloid-associated (SAA) protein (chronic inflammatory dz) (AA = A cute-phase reactant)
Type of amyloid protein: Senile cardiac Protein? Derived from...?
Protein = transthyretin Derived from AF (AF = old F ogies)
Type of amyloid protein: DM2 Protein? Derived from...?
Amylin protein Derived from AE (AE = E ndocrine)
Type of amyloid protein: Medullary carcinoma of thyroid Protein? Derived from...?
A-CAL protein Derived from calcitonin (A-CAL = CAL citonin)
Type of amyloid protein: Alzheimer's dz Protein? Derived from...?
Beta-amyloid Derived from amyloid precursor protein (APP)
Type of amyloid protein: Dialysis-associated Protein? Derived from...?
Beta-2 microglobulin Derived from MHC class I proteins.
Cells have increased in # (hyperplasia ) Abnormal proliferation of cells w/ loss of size, shape, and orientation (dysplasia ) <img src="220b.JPG" />
Neoplastic progression: step 2 In situ carcinoma
Neoplastic cells hae not invaded basement membrane. High nuclear/cytoplasmic ratio and clumped chromatin Neoplastic cells encompass entire thickness Tumor cells are monoclonal <img src="220c.JPG" />
Neoplastic progression: step 3 Invasive carcinoma
Cells have invaded basement membrane using collagenases and hydrolases Can metastasize if they reach a blood or lymphatic vessel <img src="220d.JPG" />
Neoplastic progression: step 4 Metastasis
Metastasis = Spread to distant organ Must survive immune attack. "Seed and soil" theory of metastasis: Seed = tumor embolus Soil = target organ -- liver, lungs, bone, brain... Angiogenesis allows for tumor survival Decr cadherin, incr laminin, integrin receptors <img src="220e.JPG" />
Incr in # of cells. Reversible.
1 adult cell type is replaced by another. Often 2' to irritation and/or environmental exposure (e.g., squamous metaplasia in trachea and bronchi of smokers) Reversible.
Abnormal growth w/ loss of cellular orientation, shape, and size in comparizon to normal tissue maturation; commonly preneoplastic. Reversible.
Abnormal cells lacking differentiation; like primitive cells of the same tissue, often equated w/ undifferentiated malignant neoplasms. Little or no resemblance to tissue of origin. Irreversible.
A clonal proliferation of cells that is uncontrolled and excessive. Irreversible.
Fibrous tissue formation in response to a neoplasm. Irreversible.
Degree of cellular differentiation based on histologic appearance of tumor. Usually graded I-IV based on degree of differentiation and number of mitoses per high-power field; character of tumor itself.
Degree of localization/spread based on site and size of 1' lesion, spread to regional LNs, presence of metastases; spread of tumor in a specific pt. S tage = S pread
TNM staging system
T = size of T umor N = N ode involvement M = M etastases
Which usually has more prognostic value, tumor stage or grade?
Usually stage < grade
Tumor nomenclature: Epithelium What do you call a benign tumor of this tissue? .. a malignant one?
Causes: PTH-related peptide, TGF-beat, TNF, IL-1 Effect: Hypercalcemia What neoplasm would create this paraneoplastic effect?
Squamous cell lung carcinoma, renal cell carcinoma, and breast carcinoma
Paraneoplastic effects of tumors: Renal cell carcinoma, hemangioblastoma Causes...? Effect?
Causes: Erythropoietin Effect: Polycythemia
Causes: Erythropoietin Effect: Polycythemia What neoplasm would create this paraneoplastic effect?
Renal cell carcinoma, hemangioblastoma
Paraneoplastic effects of tumors: Thymoma, small cell lung carcinoma Causes...? Effect?
Causes: Ab's against presynaptic Ca2+ channels at NMJ Effect: Lambert-Eaton syndrome (muscle weakness)
Causes: Ab's against presynaptic Ca2+ channels at NMJ Effect: Lambert-Eaton syndrome (muscle weakness) What neoplasm would create this paraneoplastic effect?
Thymoma, small cell lung carcinoma
Paraneoplastic effects of tumors: Leukemias and lymphomas Causes...? Effect?
Causes: Hyperuricemia due to excess nucleic acid (e.g., cytotoxic therapy) Effect: Gout, urate nephropathy
Causes: Hyperuricemia due to excess nucleic acid (e.g., cytotoxic therapy) Effect: Gout, urate nephropathy What neoplasm would create this paraneoplastic effect?
Leukemias and lymphomas
Laminated, concentric, calcific spherules seen in: 1.) Papillary adenocarcinoma of thyroid 2.) Serous papillary cystadenocarcinoma of ovary 3.) Meningioma 4.) Malignant mesothelioma PS aMM oma: P apillary (thyroid) S erous (ovary) M eningioma M esothelioma
Metastasis to brain
Typically multiple well-circumscribed tumors at grety-white border. Overall, approximately 50% of brain tumors are from metastases.
Primary tumors that metastasize to brain
L ung B reast S kin (melanoma) K idney (renal cell carcinoma) G I L ots of B ad S tuff K ills G lia.
Metastasis to liver
The liver and lung are the most common sites of metastasis after regional LN's. Metastasis << primary liver tumors.
Primary tumors that metastasize to liver
C olon < S tomach < P ancreas < B reast < L ung "C ancer S ometimes P enetrates B enign L iver."
Metastasis to bone
Metastatic bone tumors are far more common than primary bone tumors. L ung = lytic Prostate = blastic B reast = B oth lytic and blastic.
Primary tumors that metasize to bone
P rostate, T hyroid, T estes, B reast, L ung, K idney "P.T. B arnum L oves K ids" Metastases from breast and prostate are mosot common.
Cancer epidemiology: Lung cancer? As a cause of death overall?
Lung cancer deaths have plateaued in males, but continue to incr in females. Cancer is the 2nd leading cause of death in the USA (heart dz is 1st).