Three characteristics of apoptosis?
1) Programmed cell death
2) esinophilis in cytoplasm + cell shrinkage and fragement
3) Cell membrane remains intact without inflammation
What are functions of intrinsic apoptosis (mitochrondrial pathway) ?
1) For tissue remodeling in embryogenesis
2) Regulated by Bcl-2 family
What are the pathways for extrinsic cell death?
1) Ligand receptor interations (TNF alpha)
2) Immune cell (cytotoxic)
where is coagulative necrosis seen? Histology?
1) Ischemia and infarct
2) Histology: Increased cytoplasmic binding of acidophilic dyes
When is liquidefactive necrosis seen? Histology?
1) Bacterial abcesses
2) Neutrophils release lysosomal enzymes that digest the tissues
3) Histology: neutrophils and cell debris are seen in bacterial infection
When is caseous necrosis seen?
1) TB and fungi
2) Granular debris
3) Fragmented cells and debris surrounded by lymphocytes and macrophages.
When is fat necrosis seen?
1) enzymatic (acute pancreatitis), saponification
2) Outline of fat cells with H an E stain
When is fibrinoid necorisis seen?
1) Seen in immune reactions, polyartritis nodosa
2) Giant cell temporal arteritis
3) Vessels are think and pink
What are some changes with reversible cell injury?
this is reverisble with oxygen
1) Cell swelling (Na K+ pump injury)
2) Membrane blebbing
3) Decrease glycogen, increase fat
What are signs of irreversible cell injury?
1) Mitochrondral permeability and vacuoloziation
2) Plasma membrane damage
3) Lysosomal rupture
What are the organs most sensitive to hypoxia?
1) Brain (ACA, MCA, PCA bondaries)
2) Heart
3) Kidney
4) Liver
5) Colon
What are the different types of infarcts? Red vs. pale?
Red, reperfusion injury, when there are multiple blood supplies (liver, lung, testes)
What are the pale infarcts?
1) Single ended arterial supply (heart, kidney, spleen)
What are characteristics of inflammation?
1) red, pain, heat, swelling, and loss of function
What is the vascular vs cellular components of inflammation?
1) vascular: increased permeability, and vasodilation
What are the cellular componenets (acute) vs chronic?
1) Acute is rapid onset, and short duration (can have resolution, abcess)
2) Monocytes, and macrophages, persistent destruction, and repair with blood vessel proliferation
(going to have scarring and amyloidosis)
What is chromatolysis?
1) Neuronal cell body, axonal injury (increased protein synthesis)
2) Round cellular swelling
Can have Wallerian degeneration (degeneration of axon distal to site of injury)
What is dystrophic calcification?
Calcium deposition secondary to injury or necrosis
(Aortic stenosis)
Tuberculosis in the lungs. Not associated with the level of Ca in the body
What is metastatic calcification?
Widespread deposition of Ca in normal tissue
1) Hyperparathyroidism
2) Sarcoidosis
Hyper vitamin D
3) Metastatic calcifications (pneumonitis), patients are NOT normocalcemic
what are the steps of leucocyte extravasation?
1) Margination and rolling
2) Tight binding
3) Diapedesis
4) Migration
What is free-radical injury?
1) Lipid peroxidation, protein modification, DNA breakage
What are agents that initiate free radical injury?
1) Radiation exposure
2) Drug metabolism
3) WBC
What are diseases caused by free-radical injury?
1) Retinopathy of prematurity
2) Bronchopulmonary dysplasia
3) Drug/toxicity carbon tetrachloride (heptotoxicity)
4) Metal toxicity (hemochromatosis)
What is are possible causes of inhalation injury?
1) Smoke
2) Fire
3) Small particles or irrtiants
What are some examples of inhalation injury?
1) Tracheobronchitis
2) edema
3) Pneumonia
4) ARDS
What does bronchoscopy show on inhalation injury?
1) edema
2) congestion
3) soot deposition
How long for 80% of tensil strenth to be regained?
3 months
What are the differences between the hypertrophic vs keloid ?
Hypertrophic
1) Increased collagen synthesis
2) Confined to borders of original wound
3) Can have regression
4) Infrequent re-occurrence
Keloid
1) Increaed collagen ++++
2) Disorganized
3) Beyond borders
4) Progressive growth
Tissue mediator: PDGF?
1) Secreted by actvated platelets and macrophages
2) Induces vascular remodelling
3) Stimulates fibroblasts
Tissue mediator FGF?
Stimulates angiogenesis
Tissue mediator EGF?
Stimulates cell growth
Tissue mediator TFG-B ?
Angiogenesis
Metalloproteinases?
Tissue remodelling
VEGF?
Stimulates angiogeneis.
what are the stages of the wound healing?
1) Inflammatory (3 days after the wound): clot formation, increased vessel permability, and tissue migration
2) Proliferative (day 3 to weeks later) fibroblasts, and myoblasts (deposition of granulation, collagen, and angiogenesis)
3) Remodelling: fibroblasts, and collagen 3 give tensile strength
What are examples of granulomatous disease causes?
1) Bacterial (mycobacteria, bartonella, listeria)
2) Fungal (endemic mycoses)
3) Parasites (schistosomiasis)
4) Autoinflammatory (sarcoidosis, Crohns, Primary bilary cirrhosis, Wegners), giant cell, Takayasu.
5) Foreigh matrial: berylloiosis, talcosis
What are more common caused of caseating necrosis?
Infectious (TB)
How is sarcoidosis diagnosed?
Need to do a biopsy of sarcoidosis. (of the granulomas)
Characteristics of exudate vs transudate?
Exudate vs transudate
1) Celluar vs hypocellular
2) Increased protein vs decreased protein and LDF
3) Specific gravity > 1.02 vs
What causes the ESR to increase, and to decrease?
Increase ESR vs Decrease ESR Anemia vs sickle cell Infections vs polycythemia Inflammation vs Heart failure Cancer vs microcytosis Renal disease vs hypofibrinogenemia
what is amyloidosis characterized by?
Abnormal segregation of proteins into pleated sheets
How is amyloidosis visualized ?
By Congo stain
By Hand E stain
What are 6 types of amyloidosis?
1) AL (deposition of light chains)
2) AA (chronic inflammatory conditions sucj as RA, and IBD)
3) Dialysis related ( Fibrils of microglobulin)
4) Heritable: amyloid polyneuropathies
5) Age related: transthyretin deposited in the cardiac chambers
6) Organ specific: amyloidosis to a single organ
What is lipofuscin?
Normal wear and tear associated with aging.
In elderly person can be deposited in the heart, colon, or eye
what is cellular change, atrophy?
decrease tissue mass due to number of cells (disuse, denervation)
What is cellular change hypertrophy?
Increase in size of the cell
What is cellular change of hyperplasia?
Increase in number of cells (risk factor for future malignancy)
What is cellular change of metaplasia?
Replacement of one cell tyoe by another due to irritant.
What is neoplasia?
Clonal proliferation of cells, can be benign or malignant
What is dysplasia?
Disrodered, non neoplastic growth (only epithelial cells) severe displasia can lead to neoplasia
What is cellular differentiation?
The degree to which the malignant tumor resembles the tissue of origin. Poorly differentiated doesn’t look at all like the original tissue
What is anaplasia?
Complete lack of differentiation of cells in a malignant neoplasm.
What are the stages of neoplastic progression?
Normal cells to dysplasia, to carcinoma insity, to invasive carcinoma (This involves invasion of basement membrane using collagenase and hydrolase) Cell to cell contact lost by inactivation of E-Cadherin
What are the seed and soil theory of metastasis?
Seed:tumor embolus
Soil: Target the first organ encountered in the capillary bed
What is the different between grade and stage of tumor?
Degree of differentiation (low grade means highly differentiated)
Stage: Localized or spread
What is the TNM staging?
T = tumor size
N=Node involvement
M=Metastasis
What does carcinoma suggest?
Epithilial origin
What does sarcoma suggest?
Mesenchymal origin
What does benign suggest?
Well differentiated, well demarcated, low mitotic activity no mets
What does malignancy suggest?
Poor differentiation, erratic growth, local invasion, mets, decrease apoptosis
what are the most common male cancers?
1) Prostate
2) Lung
3) Colon
What are most common female cancers?
1) Breast
2) Lung
3) Colon
What is the highest mortality for men (cancer)?
1) Lung
2) Prostate
3) Colon
what is the highest mortality of woman (cancer)?
1) Lung
2) Breast
3) Colon
What are 2 types of paraneoplastic syndromes?
1) Acanthosis nigricans
2) Lser Trelat
3) Hypercalcemia
4) Cushing
5) Hyponatremia
6) Polycythemia
7) Red cell aplasia
8) Good syndrome
9) Trousseacu
10) endocarditis sterile plaque
11) Anti-NMDA recepter encephalitis
12) Myoclonus ataxia
13) Paraneoplastic cerebeller degeneration
14) Paraneoplastic encephalomyletis
15) Lambert-Eaton mysanthenic
16) Mysanthia gravis
What is acanthosis nigricans consist of?
Hyperpigmented plaques in axilla
Associated with gastric adenocarcinoma (and other viscral malignancies) due to insulin resistance
What are the signs of Leser Trelat? And association?
1) Multiple seborrheic keratosis
2) Associated with GI adenocarcinomas
What is the mechanism of hyercalcemia?
1) Increased PTHrP or increased 1.25 OH vitamin D
2) Squameous cell carcinoma of the lung, head, and neck, renal bladder, breast and ovarian
What is the mechanism of Cushing?
1) Increased ACTH
2) Small cell lung cancer
What is the mechanism of Hyponatremia?
1) Increased ADH
2) Small cell lung cancer
What is mechanism of polycythemia?
1) Increased erythropoietin
2) Renal cell carcinoma
3) Hepatocellular carcinoma
4) Hemangioblastoma
5) Pheochromcytoma
6) Leiomyoma
Mechanism of pure red aplasia?
1) Anemia with low reticulocytes
2) Thymoma
Mechanism good syndrome?
1) Hypogammaglogulinemia
2) Thymoma
Mechanism Trousseau syndrome?
1) Migratroy superficial thrombophlebitis
2) Adenocarcinomas (pancreatic)
Mechanism nonbacterial endocarditis?
1) Sterile plaque thrombi
2) Adenocracinomas (pancreatic)
Mechanism of Anti-NMDA receptor encephalitis?
1) Psychiatric disturbance, memory deficits, seizures, dyskinesias, autonomic instability, langage dysfunction
2) Ovarian teratoma
Mechanism of Opsoclonus, myoclonus ataxia syndrome?
1) Dancing eyes, Dancing feet
2) Neuroblastoma, small cell cancer
Paraneoplastic cerebellar degeneration?
1) Antibodies against Hu, Yo, Tr Antigens in Purkinje cells
2) Small cell cancer
3) Gynecological and breast, Hodgekins
Mechanism of paraneoplastic encephalomyelitis?
1) Antibodies against Hu antigens and neurons
2) Small cell lung cancer
what are causes of Lambert-Eaton mysanthenic syndrome?
1) Antibodies against presynaptic (P/Q type) Ca 2+
2) Small cell lung cancer
What are causes of mysanthia gravis?
1) Antibodies against post synaptic AChR at NMJ
2) Thymoma
Oncogene associated with ALK?
Lung adenocarcinoma
Oncogene associated with BCR-ABL?
CML, ALL
Oncogene with BCL-2?
Follicular and diffuse large B cell lymphoma
Oncogene with BRAF?
Melanona, non hodgkins
Oncogene with c-kit?
gastrointestinal stromal tumor (GIST)
Oncogene with m-MYC?
Burkitt’s lymphoma
Oncogene with Her2/neu (c-erbB2)
Breast and gastric carcinoma
Oncogene with JAK 2?
Chronic myeloproliferative disorders
Oncogene with KRAS?
Colon
Lung
Pancreatic
What is MYCL1?
Lung tumor
What is MYCN?
Neuroblastoma
What is RET?
Men 2A, and 2B
What is APC?
Colorectal cancer
What is BRCA1 and BRCA2?
Breast and ovarian cancer
What is CDKN2A?
Melanoma and pancreatic cancer
What is DCC?
Colon cancer (deleted in colon cancer)
What is DPC 4/SMAD4?
Pancreatic cancer
What is MEN1?
Menin
What is NF1?
Neurofibromatosis type 1
What is NF2?
Neurofibormatosis type 2
What is PTEN?
Breast cancer
Prostate cancer
Endometrial cancer
What is rb?
Retinoblastoma, osteosarcoma
What is TP53?
Most human cancers, Li-Fraumeni syndrome
What is TSC1?
Tuberous sclerosis
What is TSC2?
Tuberous sclerosis
What is VHL?
von Hippel-Lindau disease
Renal cell carcinoma
What is WT1/WT2?
Wilms Tumor.
Oncogene microbe EBV?
Burkitt lymphoma
Hodgekin’s lymphoma
Nasopharyngeal carcinoma
CNS lymphoma
Oncogene HBV, HCV?
Hepatocellular carcinoma, lymphoma
Oncogene HHV-8?
Karposi sarcoma
Oncogene HPV?
Cervical, penile/anal carcinoma (type 16 and type 18)
Oncogene H. Pylori?
Gastric Adenocarcinoma
MALT lymphoma
Oncogene HTLV-1?
Adult T cell leukemia
Oncogene Liver Fluke?
Cholangiocarcinoma
Oncogene Schistosoma haematobium?
Bladder cancer (squamous cell)
Carconogene: aflatoxins?
Hepatocellular carcinoma
Carcinogen: Alkylating agent?
Leukemia/lymphoma
Carcinogen aromatic amines?
Bladder: transitional cell carcinoma
Carcinogen Arsenic?
Angisarcoma
Lung Cancer
Squamous cell carcinoma
Carcinogenn: Asbestos?
Lung
Carcinogen tetrachloride?
Liver
Centrilobular necorisis
Carcinogen: Cigarette Smoke?
Bladder Cerivix Esophagus Kidney Larynx Lung Pancrease
Carcinogen: ethanol ?
Esophagus
Liver
Carcinogen: ionizing radiation?
Thyroid
Carcinogen: niteosamines?
Stomach cancer
Carcinogen: Radon?
Lung cancer
Carcinogen: Vinyl Chloride?
Liver (angiosarcoma)
When are Psammoma bodies seen?
Papillary carcinoma of thyroid
Serous papillary cystadenocarcinoma of the ovary
Mengingioma
Malignent mesothelioma
What are serum tumor markers used for?
Cancer diagnosis and screening (however should not be used for number 1, instead, biopsy
Can be used for tumor reoccurrence and response to therapy
Tumor marker: Alkaline phosphatase?
Mets to bone or liver
Paget disease
Seminoma ALP
Alpha fetoprotein?
Hepatocellular carcinoma
Heptoblastoma
Yolk
Mixed germ cell tumor
Tumor marker B-HCG?
Hydratiform moles
Choriocarcinomas
Testicular cancer
Mixed germ cell
Tumor marker CA 15-3/CA 27-29?
Breast cancer
Tumor marker CA 19-9?
Pancreatic adenocarcinoma
Tumor marker CA 125?
Ovarian Cancer
Tumor marker: Calcitonin?
Medullary Thyroid carcinoma
Tumor marker CEA?
CarcinoEmbyroicAntigen
Non specific
70% of pancreatic, gastric, breast
Tumor marke PSA?
Prostate specific antigen
Questionable benefit for prostate screening
Tumor marker p-glycoprotein?
Adrenal cell carcinoma
What hormones cause Cachexia?
TNF
IFN-alpha
Il-1
Il-6
How do sarcomas spread?
Hemtogenously
How is carcinoma spread?
Lymphatics
What are the most common brain mets?
Lung > Breast> prostate> melanoma> GI
What are the most common liver mets?
Colon»_space; stomach» pancrease
What are the most common bone mets?
Prostate, breast > lung, thyroid, kidney
what are the common types of breast mets?
Are usually mixed
What are the common types of lung mets?
Mixed
What are the types of kidney mets?
Lytic