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Pathology
FA complete review
| Question | Answer |
|---|---|
| Uncontrolled, clonal proliferation of cells | Neoplasia |
| What are hallmarks of cancer? | 1. Evasion of apoptosis 2. Growth signal self-sufficiency, 3. Anti-growth signal insensitivity, 4. Warburg effect, 5. Sustained angiogénesis 6. Limitless replicate potential 7. Tissue evasion 8. Metastasis |
| What is Warburg effect? | Shift of glucose metabolism away from mitochondria toward glycolysis. |
| What is the polarity of normal cells? | Apical |
| What is carcinoma in situ? | Irreversible severe dysplasia that involves the entire thickness of epithelium but does not penetrate the intact basement membrane. |
| What is another term of carcinoma in situ? | Preinvasive |
| Definition of invasive carcinoma | Cells have invaded basement membrane using collagenases and hydrolases |
| Cell-cell contacts lost by inactivation of E-cadherin | Invasive carcinoma |
| What are the means of transport of metastasis? | Lymphatics or blood |
| A carcinoma implies _______________ origin. | Epithelial |
| A sarcoma denotes ______________ origin. | Mesenchymal |
| Description of benign tumors: | Well differentiated, well demarcated, low mitotic activity, no metastasis, and no necrosis. |
| Malignant tumors may show: | Poor differentiation, erratic growth, local invasion, metastasi, and decreased apoptosis. |
| What are terms of non-neoplastic malformation? | Hamartoma and choristoma |
| Disorganized overgrowth of tissues in their native location | Hamartoma |
| What is Choristoma? | Normal tissue in foreign location |
| What would be an example of choristoma? | Gastric tissue in distal ileum in Meckel diverticulum |
| What is malignant tumor of blood cells? | Leukemia, and lymphoma |
| What is benign tumor of smooth muscle? | Leiomyoma |
| What is the common benign melanocytic tumor? | Nevus/mole |
| What is differentiation? | Degree to which a tumor resembles its tissue of origin |
| What is the definition of Anaplasia? | Complete lack of differentiation of cells in a malignant neoplasm |
| Well-differentiated tumors are ________ aggressive. | Less |
| What is meant with grande in respect to tumor classification? | Degree of cellular differentiation and mitotic activity on histology. |
| Degree of localization/spread based on site and size of primary lesion, spread to regional lymph nodes, presence of metastases. | Stage |
| TNM staging system | T = Tumor size/invasiness N = Node involvement M = Metastases |
| Each TNM factor has ---> | Independent prognostic value |
| What are musculoskeletal and cutaneous paraneoplastic syndrome? | 1. Dermatomyositis 2. Acanthosis nigricans 3. Sign of Leser-Trélat 4. Hypertrophic osteoarthropathy |
| What are the associated tumors in Dermatomyositis? | Adenocarcinomas, especially ovarian |
| What are the most common associated tumors of Acanthosis nigricans? | Gastric adenocarcinoma and other visceral malignancies |
| Hypertrophic osteoarthropathy is seen with adenocarcinoma of the __________. | Lung |
| What is the description Hypertrophic osteoarthropathy? | Abnormal proliferation of skin and bone at distal extremities --> clubbing, arthralgia, joint effusions, periostosis of tubular bones. |
| Small cell lung cancer is associated with which Paraneoplastic syndromes? | Cushing syndrome and Hyponatremia (SIADH) |
| What are some common hematologic paraneoplastic syndromes? | Polycythemia, Pure red cell aplasia Good syndrome Trousseau syndrome Nonbacterial thrombotic (marantic) endocarditis |
| Thymoma is associated with which hematologic conditions? | Pure red cell aplasia and Good syndrome |
| What is the "Good syndrome" most significant clinical feature? | Hypogammaglobulinemia |
| Trousseau syndrome is most associated with ____________ (tumor). | Pancreatic adenocarcinoma |
| Associated tumors that produce Polycythemia | Pheochromocytoma, Renal cell carcinoma, HCC, Hemangioblastoma, and Leiomyoma. |
| List of Neuromuscular Paraneoplastic syndromes: | 1. Anti-NMDA receptor encephalitis 2. Opsoclonus-myoclonus ataxia syndrome 3. Paraneoplastic cerebellar degeneration 4. Paraneoplastic encephalomyelitis 5. Lambert-Eaton myasthenic syndrome 6. Myasthenia gravis |
| What neuromuscular paraneoplastic syndrome is associated with Thymoma? | Myasthenia gravis |
| Lambert-Eaton Myasthenic syndrome is associated with which tumor? | Small cell lung cancer |
| Antibodies against presynaptic Ca2+ channels at NMJ. Dx? | Lambert-Eaton Myasthenic syndrome |
| What is the cause of Myasthenia gravis? | Antibodies against postsynaptic ACh receptors at NMJ |
| What condition affects the PREsynaptic calcium channels at NMJ? | Lambert-Eaton Myasthenic syndrome |
| Which condition is seen with antibodies attacking the POSTsynaptic ACh receptors? | Myasthenia gravis |
| "Dancing eyes, dancing feet". Dx? | Opsoclonus-myoclonus ataxia syndrome |
| Which are the tumors associated with the development of Opsoclonus-myoclonus ataxia syndrome? | Neuroblastoma in children and Small cell lung cancer in adults |
| Antibodies against antigens in Purkinje cells. Dx? | Paraneoplastic cerebellar degeneration |
| What are the associated tumors of Paraneoplastic cerebellar degeneration? | 1. Small cell lung cancer (anti-Hu) 2. Gynecologic and breast cancers (anti-Yo) 3. Hodgkin lymphoma (anti-Tr) |
| Anti-Hu, anti-Yo, and anti-Tr. | Markers of tumors seen in the development of Paraneoplastic cerebellar degeneration |
| Ovarian teratoma often causes what neuromuscular paraneoplastic syndrome? | Anti-NMDA receptor encephalitis |
| List of Paraneoplastic syndromes associated with Small cell lung cancer: | 1. Hypertrophic osteoarthropathy 2. Cushing syndrome 3. SIADH 4. Opsonus-myoclonus ataxia syndrome 5. Paraneoplastic cerebellar degeneration 6. Paraneoplastic encephalomyelitis 7. Lambert-Eaton Myasthenic syndrome |
| Clinical signs include: Psychiatric disturbances, memory deficits, seizures, dyskinesias, autonomic instability, and language dysfunction. Associated with Ovarian tumor. Dx? | Anti-NMDA receptor encephalitis |
| Which are some of the tumors or neoplasms that produce Hypercalcemia (due to increased PTHrP) as Paraneoplastic syndrome? | 1. Squamous cell carcinoma of lung, head, and neck 2. Renal, bladder, breast, and ovarian carcinomas |
| EBV associated cancers: | 1. Burkitt lymphoma 2. Hodgkin lymphoma 3. Nasopharyngeal carcinoma 4. Primary CNS lymphoma (immunocompromised) |
| Burkitt lymphoma is often see with what kind of infectious agent? | EBV |
| What does Burkitt lymphoma, Nasopharyngeal carcinoma, and Primary CNS lymphoma have in common? | Associated with EBV infection |
| Which hepatitis infections are associated with HCC? | HBV and HCV |
| Associated cancer of HHV-8 infection? | Kaposi sarcoma |
| HPV ----> associated cancers? | Cervical and penile/anal cancers (types 16,18), head and neck cancer. |
| What infection is often associated to Gastric adenocarcinoma? | H. pylori |
| H. pylori infection is associated with which tumors? | Gastric adenocarcinoma and MALT lymphoma |
| HTLV-1 infections ----> Tumor? | Adult T-cell leukemia/lymphoma |
| What microbe is associated with Cholangiocarcinoma? | Liver fluke (Clonorchis sinensis) |
| Squamous bladder cancer is often described with preceding infection of: | Schistosoma haematobium |
| Aflatoxin exposure examples: | Stored in grains and nuts |
| What is the associated carcinoma of Aflatoxin exposure? | Hepatocellular carcinoma |
| What are examples of aromatic amine exposure? | 1. Textile industry (dyes) 2. Cigarette smoke (2-naphthylamine) |
| Aromatic amines cause ______________ cancer. | Bladder cancer |
| What kind of bladder cancer is seen with exposure to industrial textile dyes? | Transitional cell carcinoma of the bladder |
| Benzidine and 2-naphthylamine are examples of : | Aromatic amines |
| What are common Arsenic exposures examples? | Herbicides (vineyard workers), and metal smelting |
| Arsenic exposure causes damage to which organs? | Liver, Lung, and Skin |
| Associated cancer of arsenic exposures and affection to the liver | Angiosarcoma |
| Person with arsenic exposure. What is the cutaneous cancer association? | Squamous cell carcinoma of the skin |
| Which jobs are often associated with Asbestos exposure? | 1. Old roofing material 2. Shipyard workers |
| What organ is mostly affected by Asbestos exposure? | Lung |
| Which cancer is most common in Asbestos exposures? | Bronchogenic carcinoma |
| What are the two associated tumors/cancers with Asbestos exposure? | Bronchogenic carcinoma>>>> Mesothelioma |
| What type of bladder cancer is due to cigarette smoking? | Transitional cell carcinoma |
| Which are the associated cancers of the lung due to cigarette smoking? | Squamous cell and Small cell carcinoma |
| Cigarette smoking may cause what kidney cancer? | Renal cell carcinoma |
| What is the neoplastic manifestation of cigarette smoking and affection in the Esophagus? | Squamous cell carcinoma/adenocarcinoma |
| What organs are most affected by excessive ethanol consumption? | Esophagus and Liver |
| Ionization radiation to the Thyroid is associated with development of: | Papillary thyroid cancer |
| What is an important risk factor for development of Papillary thyroid carcinoma? | Ionizing radiation |
| What kind of toxin is presented with smoked foods? | Nitrosamines |
| Nitrosamine consumption is associated with ____________ cancer. | Gastric |
| What is the neoplastic relevant toxin found in material used to make PVC pipes? | Vinyl chloride |
| What kind of worker/job is most likely to be in exposures with Vinyl chloride (toxin)? | Plumber/plumbing |
| Vinyl chloride exposure affects the _____________ leading to development of __________________. | Liver ----> angiosarcoma |
| What are Psammoma bodies? | Laminated, concentric spherules with dystrophic calcification |
| What are conditions/cancers seen with Psammoma bodies? | Papillary carcinoma of thyroid Serous papillary cystadenocarcinoma of ovary Meningioma Malignant Mesothelioma |
| Why type of thyroid cancer is seen with Psammoma bodies? | Papillary carcinoma of thyroid |
| Which ovarian carcinoma is seen with Psammoma bodies? | Serous cystadenocarcinoma of ovary |
| Which type of asbestos-related cancer is seen with Psammoma bodies? | Malignant Mesothelioma |
| What is the most important/relevant histologic feature of Papillary thyroid carcinoma? | Psammoma bodies |
| What histological finding can further distinguish between Bronchogenic carcinoma and Mesothelioma? | Psammoma bodies in Mesothelioma |
| What should be the use of serum tumor markers? | Monitor tumor recurrence and response to therapy |
| What is used to monitor tumor recurrence and response to therapy? | Levels of serum tumor markers |
| What procedure should be the one used for definitive diagnosis of cancer? | Biopsy |
| What the important associations of Alkaline Phosphatase? | 1. Metastases to bone or liver, 2. Paget disease of the bone 3. Seminoma (placental ALP) |
| What is the common abbreviation for Alkaline Phosphatase? | ALP |
| Elevated placental ALP is seen in __________________. | Seminoma |
| Elevation in sumru tumor marker, ALP, is seen with metastases to ___________ or _________. | Bone or liver |
| How can ALP be distinguished or separated from hepatic origin? | Exclusion of hepatic origin by checking LFTs and GGT levels |
| Why are LFTs and GGTs levels often measured in cases of elevated ALP? | To exclude is ALP is of liver origin. |
| List of associations seen with elevated a-Fetoprotein: | 1. Hepatocellular carcinoma 2. Endodermal sinus (yolk sac) tumor 3. Mixed germ cell tumor 4. Ataxia-telangiectasia 5. Neural tube defects |
| Low levels of AFP are seen with? | Down syndrome |
| What kind of defects are seen with high levels of AFP? | Neural tube and abdominal wall defects |
| Which endodermal sinus tumor is seen with elevated AFP? | Yolk sac tumor |
| Elevated B-hCG is seen with: | - Hydatiform moles -Choriocarcinomas - Testicular cancer - Mixed germ cell tumor |
| Which tissue normally produces B-hCG? | Syncytiotrophoblasts of the placenta |
| Tumor markers for Breast cancer: | CA 15-3/CA 27-29 |
| Tumor marker of Pancreatic adenocarcinoma? | CA 19-9 |
| CA 125, is an _________________ cancer serum tumor marker. | Ovarian |
| What serum marker is used in Ovarian cancer? | CA 125 |
| What is the most common serum marker used for Medullary thyroid cancer? | Calcitonin |
| Which syndromes are seen with elevated Calcitonin? | MEN2A and MEN2B |
| What are the two major associations of CEA? | Colorectal and Pancreatic cancers |
| What are minor associations of CEA tumor marker? | Gastric, breast, and medullary thyroid carcinomas |
| CEA is the abbreviation for: | Carcinoembryonic antigen |
| What type of tumors use Chromogranin as a serum tumor marker? | Neuroendocrine tumors |
| LDH is a serum tumor marker for which cancers? | Testicular germ cell tumors Ovarian dysgerminoma |
| PSA is seen elevated in _____________ cancer. | Prostate |
| LDH is elevated in which ovarian cancer? | Ovarian dysgerminoma |
| Which testicular cancers result in elevated LDH leves? | Testicular germ cell tumors |
| Prostate-specific antigen is abbreviated ___________. | PSA |
| What other non-neoplastic conditions elevate PSA? | BPH adn prostatitis |
| Why are immunohistochemical stains important in cancerous processes? | 1. Determine primary site of origin for metastatic tumors 2. Characterize tumors that are difficult to classify |
| Immunohistochemical stains may have what important characteristic/ values? | Prognostic and predictive values |
| What is Vimentin's (stain) target? | Mesenchymal tissue |
| What stain is used to identify Mesenchymal tumors? | Vimentin |
| List of important immunohistochemical stains: | Vimentin, S-100 Desmin Cytokeratin GFAP Neurofilament PSA TRAP Chromogranin and synaptophysin |
| What is the target of S-100 stain? | Neural crest cells |
| What stain is used to identify neural crest cells? | S-100 |
| What are common (+) S-100 tumors? | Melanoma, Schwannoma, Langerhans cell histiocytosis |
| Melanoma and Schwannoma are both (+) for ___________. (stain) | S-100 |
| What is the most common immunohistochemical stain used for muscle tumors? | Desmin |
| What is stain/targeted by desmin (immunohistochemical stain)? | Muscle |
| What is Desmin? | Important immunohistochemical stain of muscles |
| What are common cells identified as (+) GFAP? | Astrocytes, Schwann cells, and Oligodendrocytes |
| What is the target of GFAP stain? | Neuroglia |
| What are the two most important (+) GFAP tumors? | Astrocytoma and Glioblastoma |
| What immunohistochemical stain can be used to ID Neurons and Neuronal tumors? | Neurofilament |
| Neuroblastoma is (+) for what immunohistochemical stain? | Neurofilament |
| What is the target for stain PSA? | Prostatic epithelium |
| Prostatic epithelium is stain by ____________. | PSA |
| Hairy cell leukemia is (+)___________. | TRAP |
| (+) TRAP. Dx? | Hairy cell leukemia |
| What are common tumors identified by (+) chromogranin and synaptophysin stains? | 1. Small cell carcinoma of the lung 2. Carcinoid tumor |
| What is another name for P-glycoprotein? | Multidrug resistance protein 1 (MDR1) |
| What is the function of P-glycoprotein? | Pump out toxins, including chemotherapeutic agents |
| Why is P-glycoprotein considered a "resistance" factor to chemotherapy? | It causes the pump-out of toxins, including those chemotherapeutic agents --> decreased response to therapy. |
| What is the most common cancer to show elevated levels of P-glycoprotein? | Adrenocortical carcinoma |
| What is cachexia? | Weight loss, muscle atrophy, and fatigue that occur in chronic disease. |
| What are the cytokines that mediate cachexia? | TNF, IFN-gamma, IL-1, and IL-6. |
| What is the most common cancer? | Skin cancer |
| What is the most common type of skin cancer? | Basal >Squamous >> melanoma |
| What is the highest incidence cancer in men? | Prostate |
| What is the top 3 cancer mortality in men? | Lung > Prostate > Colon/ rectum |
| What is the number 1 cancer incidence in women? | Breast |
| Leukemia is the cancer with highest incidence and mortality in ______________. | Children (0-14 years) |
| What is the 2nd leading cause of death in the United States? | Cancer |
| What is the leading cause of death in the USA? | Heart disease |
| What is the leading cancer mortality in men and women? | Lung |
| What are the top 3 cancer incidence and mortality in children? | Leukemia > CNS > Neuroblastoma |
| What are 50% of brain tumors? | Arise from metastases |
| What are the most common primary tumors that metastasizes to brain? | Lung > breast > melanoma, colon, and kidney. |
| What type of primary tumor metastases to liver the most? | Colon |
| What are the most common sites of metastasis after regional lymph nodes? | Liver and lung |
| Gene prodcut of ALK | Receptor tyrosine kinase |
| What are the associated neoplasms of ALK? | Lung adenocarcinoma |
| What is the gen product of BCR-ABL? | Tyrosine kinase |
| What are the associated neoplasms of BCR-ABL gene? | CML, ALL |
| CML is due to which gene? | BCR-ABL |
| What is the associated neoplasm of BCL-2? | Follicular and diffuse large B cell lymphomas |
| What is the associated gene product of Follicular and diffuse large B cell lymphoma? | Antiapoptotic molecule |
| What is the gene product of Bcl-2? | Antiapoptotic molecule |
| What is the role or function of antiapoptotic molecule? | Inhibits apoptosis |
| What gene is associated with Diffuse large B cell lymphoma? | Bcl-2 |
| Gain of function mutation converts proto-oncogene to oncogene. | Oncogene function |
| Need damage to only one allele | Oncogene |
| What is the gene product of BRAF? | Serine/threonine kinase |
| What are the associated neoplasms of gene BRAF? | Melanoma, non-Hodgkin lymphoma, papillary thryroid carcinoma |
| GIST associated gene? | c-KIT |
| What is the gene product of c-KIT? | Cytokine receptor |
| Cytokine receptor is the gene prodcut of which gene? | c-KIT |
| What is the associated gene of Gastrointestinal stromal tumor? | c-KIT |
| c-MYC produce asn ___________________ (gene product). | Transcription factor |
| What is the associated neoplasm of c-MYC? | Burkitt lymphoma |
| Burkitt lymphoma is due to a _____________ produced by c-MYC. | Transcription factor |
| What is the HER2/neu (c-erbB2) gene product? | Receptor tyrosine kinase |
| Which genes have Receptor tyrosine kinase as gene product? | RET, HER2/neu , and ALK. |
| Associated neoplasm of JAK2 gene? | Chronic myeloproliferative disorders |
| What cancers are associated with gen KRAS? | Colon, lung, and pancreatic cancers |
| Which transcription factor (gene) is associated with Lung tumor? | MYCL1 |
| N-myc gene makes a transcription factor and is associated with __________________. | Neuroblastoma |
| RET gene is involved in which neoplasms? | MEN 2A and 2B, and papillary thyroid carcinoma |
| Loss of function refers to tumor suppressor or oncogenes? | Tumor suppressor genes |
| Both alleles of need to mutated for expressivity of disease | Tumor suppressor gene |
| APC is a ____________________________ gene. | Tumor suppressor |
| What is the associated condition of APC (gene)? | Colorectal cancer |
| How does APC cause colorectal cancer? | Negative regulator of B-catenin/WNT pathway |
| Which are two common DNA repair proteins associated with Breast, ovarian, and pancreatic cancer? | BRCA1/BRCA2 |
| What are the associated neoplasms of CDKN2A? | Melanoma and Pancreatic cancer |
| Colon cancer is associated with which tumor suppressor gene? | DCC |
| Gene APC refests to _______________________ cancer, and DCC is associated with ______________ cancer. | APC ----> colorectal DCC ------> colon |
| Deleted in Colon Cancer | DCC |
| Deleted n Pancreatic Cancer | DCP |
| DCP is the gene product of which specific gene? | SMAD4 (DPC4) |
| Gene product of MEN1? | Menin |
| Gene product of NF2? | Merlin (schwannomin) protein |
| Ras GTPase activating protein | Neurofibromin |
| What is the role PTEN? | Negatively regulates PI3K/AKT pathway |
| What are the associated neoplasm of PTEN? | Breast, Prostate, and endometrial cancer |
| What is the product or function of Rb? | Inhibits EF2; Blocks G1 ---> S phase transition |
| Retinoblastoma and Osteosarcoma are both associated with ____, a tumor suppressor gene. | Rb |
| Which are the most important Rb-associated neoplasms? | Retinoblastoma and Osteosarcoma |
| What is the role of TP53 gene? | Its gene product is p53, which activates p21, and blocks G1 --S phase transition. |
| What tumor suppressor gene is often affected in most human cancers? | TP53 |
| What syndrome is due to mutated TP53 tumor suppressor gene? | Li-Fraumeni syndrome |
| What malignancies are associated with Li-Fraumeni syndrome? | Sarcoma, Breast, Leukemia, and adrenal gland |
| SBLA is another way to refer to: | Li-Fraumeni syndrome |
| What is the the associated tumor suppressor gene and gene product of Tuberous sclerosis? | TSC1; Hamartin protein |
| What are the two associated proteins in the development of Tuberous sclerosis? | Tuberin and Hamartin proteins |
| What is the role of VHL? | Inhibits hypoxia inducible factor 1a |
| What condition is associated with VHL? | von Hippel-Lindau disease |
| Mutated tumor suppressor gene WT1 causes --> | Wilms tumor (nephroblastoma) |
| What is the role of WT1 gene? | Transcription factor that regulates urogenital development |
| What are cellular adaptations? | Reversible changes that can be physiologic or pathologic |
| What is Hypertrophy? | Increase structural proteins and organelles --> increase in size of cells |
| The cellular adaptation the causes increase in size of cells | Hypertrophy |
| What type of cellular adaptation results in increase number of cells? | Hyperplasia |
| What is hyperplasia? | Controlled proliferation of stem cells and differentiated cells --> increase in number of cells |
| What can be complications of excessive cell stimulation? | Pathological hyperplasia, which may progress to dysplasia and cancer |
| Definition of atrophy | Controlled tissue mass due to decrease in size and/or number of cells |
| How is a decrease in tissue mass due to decrease size done? | Increase cytoskeleton degradation via ubiquitin-proteasome pathway and autophagy. |
| What are some actions that lead to atrophy? | Disuse, denervation, loss of blood supply, loss of hormonal stimulation, and poor nutrition |
| Reprogramming of stem cells --> replacement of one cell type by another that can adapt to a new stress. | Metaplasia |
| What cellular adaptation occurs when one cell type is replaced by another? | Metaplasia |
| What are some common causes of metaplasia? | Cigarette smoking and irritation by gastric acid |
| What is dysplasia? | Cellular adaptation consisting of disordered , precancerous epithelial cell growth. |
| Loss of uniformity of cell size and shape; loss of orientation; nuclear changes. | Dysplasia |
| Precancerous epithelial uncontrolled growth. | Dysplasia |
| Severe dysplasia: | Usually becomes irreversible and progresses to carcinoma in situ. |
| Carcinoma in situ are commonly due to severe _______________. | Dysplasia |
| What nuclear irreversible cell injury changes? | 1. Pyknosis (condensation) 2. Karyorrhexis (fragmentation) 3. Karyolysis (fading) |
| What are clinical terms for Nuclear condensation, fragmentation, and fading? | Pyknosis, Karyorrhexis, and Karyolysis |
| Cellular membrane blebbing and nuclear chromatin clumping are examples of: | Reversible cell injury manifestations |
| Definition of Apoptosis: | ATP-dependent programmed cell death |
| Does Apoptosis require ATP? | Yes, it is a ATP-dependent activity |
| Apoptosis as ______________ and ______________ pathways. | Intrinsic and Extrinsic |
| What are the shared features between the intrinsic and extrinsic pathways of apoptosis? | Activate caspases --> cellular breakdown including cell shrinkage, chromatin condensation, membrane blebbing, and formation of apoptotic bodies, which are then phagocytosed. |
| What cellular action is characterized by deeply eosinophilic cytoplasm and basophilic nucleus, pyknosis, and karyorrhexis? | Apoptosis |
| How does Karyorrhexis occurs in apoptosis? | Fragmentation caused by endonuclease-mediated cleavage. |
| What is different in respect cell membrane between apoptosis and necrosis? | In apoptosis the cell membrane remains intact without significant inflammation. |
| What is an important and sensitive indicator of apoptosis? | DNA laddering |
| What is DNA laddering? | Fragments in multiples of 180 bp |
| The mitochondrial pathway refers to the ______________ pathway of apoptosis. | Intrinsic |
| When does the intrinsic pathway of apoptosis occurs? | As a regulating factor is withdrawn from a proliferating cell population. |
| What regulates the Intrinsic pathway of apoptosis? | Regulated by Bcl-2 family of proteins |
| Two PRO-apoptotic proteins: | BAX and BAK |
| Which Bcl-2 family proteins are anti-apoptotic? | Bcl-2 and Bcl-xL |
| What is the function of BAX and BAK? | Form pores in the mitochondrial membrane --> release of cytochrome C from inner mitochondrial membrane ito cytoplasm --> activation of caspases |
| Due to mitochondrial pore formation due to proapoptotic proteins what gets activated? | Caspases |
| What are caspases? | Cytosolic proteases |
| Caspase activation is associated with _______________. | Apoptosis |
| How does Bcl-2 prevent apoptosis? | Keeps mitochondrial membrane impermeable, thereby preventing cytochrome C release. |
| Bcl-2 overexpression ------->? | Decrease caspase activation ---> tumorigenesis |
| What are the two pathways of the Extrinsic Pathway of apoptosis? | 1. Ligand receptor interactions 2. Immune cell |
| What are the Ligand receptor interactions of the Extrinsic paths of apoptosis? | 1. FasL binding to Fas, or, 2. TNF-alpha binding to its receptor |
| What is the Immune cell pathway of the extrinsic apoptotic pathway? | Cytotoxic T-cell release of perforin and granzyme B |
| Fas-FasL interaction is necessary for: | Thymic medullary negative selection |
| What is the result of mutations in Fas? | Increased numbers of circulating self-reactive lymphocytes due to failure of clonal deletion |
| What is the result of defective Fas-FasL interactions? | Autoimmune lymphoproliferative syndrome |
| Necrosis is an ________________ process unlike apoptosis. | Inflammatory |
| What is the definition of Necrosis? | Enzymatic degradation and protein denaturation of cell due to exogenous injury --> intracellular components leakage. |
| When is Coagulative necrosis seen? | Ischemia/infarcts in most tissues (except brain) |
| Which is a tissue that does not show coagulative necrosis? | Brain |
| Coagulative necrosis is due to: | Ischemia or infarction; injury denatures enzymes ---> proteolysis blocked |
| Which type of necrosis is seen with Proteolysis blocked? | Coagulative necrosis |
| Histology of Coagulative necrosis: | Preceserved cellular architecture but nuclei disappear; Increased cytoplasmic binding of eosin stain |
| Histological view presents preserved cellular architecture, no nuclei, and increase cytoplasmic binding of eosin stain. | Coagulative necrosis |
| Liquefactive necrosis is seen with: | Bacterial abscesses and brain infarcts |
| What kind of necrosis is seen in brain infarcts? | Liquefactive necrosis |
| Why does liquefactive necrosis occur? | Neutrophils release lysosomal enzymes that digest the tissue |
| What are the main WBC type that carry out Liquefactive necrosis? | Neutrophils |
| What is the late histological view of Liquefactive necrosis? | Cystic spaces and cavitation (brain) |
| Which infections/conditions are seen with Caseous necrosis? | TB, systemic fungi (histoplasma capsulatum), and Nocardia |
| Macrophages wall off infecting microorganism --> granular debris. | Caseous necrosis pathogenesis |
| What is the histological features of Caseous necrosis? | Fragmented cells and debris surrounded by lymphocytes and macrophages. |
| Which type of necrosis is seen with the formation of granulomas? | Caseous necrosis |
| What are the main type of cells involved in Caseous necrosis? | Macrophages |
| Fat Necrosis is seen with: | 1. Enzymatic: acute pancreatitis 2. Nonenzymatic: Traumatic |
| Why does acute pancreatitis cause Fat necrosis? | Saponification of peripancreatic fat |
| Fat necrosis is due to; | Damaged cells release lipase, wich brask down triglycerides; liberated fatty acids bind calcium ---> SAPONIFICATION |
| Saponification is associated with _____________ necrosis. | Fat |
| Fat necrosis histological features | - Outlines of dead fat cells without peripheral nuclei - Saponification of fat appears dark blue on H&E stain |
| Vessel walls are thick and pink. Description of histological feature of ______________ necrosis. | Fibrinoid |
| What conditions produce Fibrinoid necrosis? | Immune reactions in vessels, preeclampsia, hypertensive emergency |
| How is fibrinoid necrosis produced? | Immune complexes combine with fibrin leading to vessel wall damage |
| Fibrinoid necrosis is considered what kind of hypersensitivity reaction? | Type 3 |
| What type of necrosis is seen in distal extremity and GI tract, after chronic ischemia? | Grangenous necrosis |
| Dry gangrenous necrosis is due to _________________. | Ischemia |
| Wet gangrenous necrosis is due to ________________. | Superinfection |
| Inadequate blood supply to meet demand. | Ischemia |
| What are the mechanisms that involve ischemia? | 1. Decreased arterial perfusion 2. Decreased venous drainage 3. Shock |
| What organ is the most vulnerable to hypoxia/ischemia? | Brain |
| What areas are of the brain most susceptible to hypoxia/ischemia? | ACA/MCA/PCA boundary areas |
| What are the most vulnerables regions to hypoxia? | Brain> Heart> Kidney> Liver> Colon |
| What type of cells are most affected by hypoxia? | Neurons, especially those include Purkinje cells of the cerebellum and pyramidal cells of the hippocampus and neocortex |
| What are two main types of infarcts? | Red infarcts and Pale infacts |
| What is another name for red infarcts? | Hemorrhagic infarcts |
| Red infarcts are due to: | Venous occlusion and tissues with multiple blood supplies, such as liver, lung, intestine, testes |
| What is the main concept behind the development of a red infarct? | Reperfusion |
| Damage or injury due to reperfusion is due to _________________. | Free radicals |
| What is another name for Pale infarcts? | Anemic |
| Which type of organs produce pale infarcts? | Solid organs with a single blood supply, such as heart, kidney, and spleen. |
| Which are the most common organs that have red infarcts? | Liver, lung, intestines, and testes |
| Heart, kidney, and spleen are often seen with __________ infarcts. | Pale |
| An organ with an end-arterial blood supply will most likely suffer on what kind of infarct? | Pale infarct |
| What is inflammation? | Response to eliminate initial cause of cell injury, to remove necrotic cells resulting from the original insult, and to initiate tissue repair. |
| What are the two main divisions of the inflammatory process? | Acute and chronic |
| What conditions lead to a harmful inflammatory response to itself (host)? | If it is: 1. Excessive (septic shock) 2. Prolonged (TB) 3. Inappropriate (autoimmune disease such as SLE) |
| What are the cardinal signs of inflammation? | 1. Rubor (redness), calor (warthm) 2. Tumor (swelling) 3. Dolor (pain) 4. Functio laesa (loss of function) |
| How is the rubor and calor developed in the inflammatory response? | Vasodilation (relaxation of arteriolar smooth muscle) --> increased blood flow. |
| What are the mediators of redness and warmth in inflammation? | Histamine, prostaglandins, and bradykinin. |
| What is the mechanism of action of Swelling caused by the inflammatory process? | Endothelial contraction/disruption --> increased vascular permeability --> leakage of protein-rich fluid from postcapillary venules into interstitial space (exudate) --> incrase in oncotic pressure |
| What is the end result of the process of swelling caused by inflammation? | Increased oncotic pressure due to increased level of proteins in the interstitial space. |
| What mediators cause or regulate endothelial contraction? | Leukotrienes (C4, D4, E4), histamine, and serotonin. |
| Sensitization of sensory nerve endings | Dolor (pain) |
| What are the mediators for dolor? | Bradykinin and PGE2 |
| What are the 3 systemic manifestations of inflammation? | Fever, leukocytosis, and increased plasma acute-phase reactants |
| When is leukocytosis commonly seen? | As a systemic manifestation of inflammation |
| What is leukocytosis? | Elevation of WBC count |
| What is a leukemoid reaction? | Severe elevation in WBC (> 40,000 cells) caused by some stressors or infections |
| What is the initial step in the pathogenesis of fever? | Pyrogens (LPS) induced macrophages to release IL-1 and TNF |
| Fever causes an increase in ______ in perivascular cells of the _______________. | COX activity ; Hypothalamus |
| What areas of the CNS is associated with the development of fever? | Hypothalamus |
| Which interleukin is notably for inducing acute phase reactants? | IL-6 |
| Where are acute-phase reactants produced? | Liver |
| Which are the POSITIVE acute phase reactants? | Ferritin, Fibrinogen, Serum amyloid A, Hepcidin, and C-reactive protein |
| Positive acute phase reactants _____________________. | Upregulate |
| What are the two most significant negative (downregulated) acute phase reactants in the process of inflammation? | Albumin and Transferin |
| Albumin and Transferrin are important ___________________. | Negative acute-phase reactants |
| What is the role of ferritin? | Binds and sequesters iron to inhibit microbial iron scavenging |
| What protein is known to inhibit microbial iron scavenging? | Ferritin |
| Ferritin binds to __________. | Iron |
| What is a coagulation factor, that is also a positive acute phase reactant? | Fibrinogen |
| Promotes endothelial repair; correlates with ESR; Coagulation factor involved in inflammatory process? | Fibrinogen |
| The level of fibrinogen is correlated with the amount of _______. | ESR |
| What are the two main roles of Hepcidin? | 1. Decrease iron absorption 2. Decrease iron release from macrophages |
| How does hepcidin decrease the amount of iron absorption? | Degrating ferroportin |
| What acute phase reactant is known to degrade ferroportin? | Hepcidin |
| The actions (prolonged) of hepcidin will result in the development of ___________________________. | Anemia of chronic disease (ACD) |
| C-reactive protein is an _________________________. | Opsonin |
| What is the main action or role of C-reactive protein? | Fixes complement and facilitates phagocytosis |
| Nonspecific sign of ongoing inflammation | C-reactive protein |
| What is the role of Albumin as an negative acute phase reactant? | Reduction conserves amino acids for positive reactants |
| Which two acute phase reactants are seen in lower levels during inflammation? | Albumin and Transferrin |
| What is the main reason for the low levels of albumin during inflammation? | Conservation of amino acids needed for positive reactants |
| What is the role of Transferrin (downregulated) during inflammation? | Internalized by macrophages to sequester iron |
| What is the abbreviation for Erythrocyte Sedimentation Rate? | ESR |
| What is ESR? | Products of inflammation coat RBCs and cause aggregation |
| The denser RBC aggregates ----> | Fall at a faster rate within a pipette tube --> Increase ESR |
| What is often co-tested with CRP levels? | ESR |
| What are common conditions with elevated ESR? | 1. Most anemias 2. Infections 3. Inflammation 4. Cancer 5. Renal disease (ESD or nephrotic syndrome) 6. Pregnancy |
| Which is the only anemia with a decreased ESR? | Sickle cell anemia |
| What product of inflammation is downregulated or lower in Sickle cell anemia? | ESR |
| Why is Sickle cell anemia manifested with a decreased ESR? | Altered shape of the RBC |
| List of conditions with decreased levels of ESR | 1. Sickle cell anemia 2. Polycythemia 3. Heart failure 4. Microcytosis 5. Hypofibrinogenemia |
| What is decreased in Polycythemia, heart failure, and microcytosis? | ESR |
| What WBC characterize acute inflammation? | Neutrophils in tissue |
| Acute inflammation is a manifestation of the ___________ immune system. | Innate |
| What is the most common clinical manifestation of acute inflammation? | Edema |
| Which are the MC mediators of acute inflammation? | Toll-like receptors, arachidonic acid metabolites, neutrophils, eosinophils, antibodies, mast cells, basophils, complement, and Hageman factor |
| What is the name of Factor XII? | Hageman factor |
| What is an inflammasome? | Cytoplasmic protein complex that recognizes procedures of dead cells, microbial products, and crystals |
| What is the result of an inflammasome activity? | Activation of IL-1 and inflammatory response |
| What is the vascular component of acute inflammation? | Vasodilation and endothelial permeability |
| What is the cellular component of acute inflammation? | Extravasation of leukocytes from postcapillary venules and accumulation in the focus of injury followed by leukocyte activation |
| What is the purpose of vasodilation in acute inflammation? | Bring cells and proteins to site of injury or infection |
| What are the 4 steps in leukocyte extravasation? | 1. Margination and rolling 2. Adhesión 3. Transmigration 4. Migration (chemoattraction) |
| What cells predominate in the late states of acute inflammation? | Macrophages |
| Which Interleukin indicates persistent acute inflammation? | IL-8 |
| What is the result of acute inflammation progressing into chronic inflammation? | Antigen presentation by macrophages and other APCs --> activation of CD4+ Th cells |
| Where does most of leukocyte extravasation occur? | Postcapillary venules |
| What condition is associated with defective Margination and Rolling, step of extravasation? | Leukocyte adhesion deficiency type 2 |
| What leukocyte component is decreased /absent/nonfunctional in LAD type 2? | Sialyl-Lewis x |
| Which proteins, serum markers are involved in Margination and rolling step of Leukocyte extravasation? | E-selectin, P-selectin, and GlyCAM-1, CD34 |
| What is another way to refer to adhesion step in Extravasation of leukocytes? | Tight binding |
| Defective Adhesion step in Leukocyte extravasation process leads to development of ___________________. | Leukocyte adhesion deficiency type 1 |
| LAD 2 is due to defective step ___ in Leukocyte extravasation | 1 |
| LAD type 1 is due to defective step ___ in leukocyte extravasation. | 2 |
| Decreased CD18 integrin subunit is seen in : | Leukocyte adhesion deficiency type 1 |
| ICAM-1 and VCAM-1 are involved in: | Tight binding (adhesion) step of Leukocyte extravasation |
| CD54 indicates? | ICAM-1 |
| CD106 indicates? | VCAM-1 |
| PECAM is represented by CD_. | 31 |
| What is another term used for transmigration? | Diapedesis |
| Description of Diapedesis (step 3) in Leukocyte extravasation | WBC travels between endothelial cells and exits blood vessel |
| What happens during migration (step 4) of WBC extravasation? | WBC travels through interstitium to site of injury or infection guided by chemotactic signals |
| What are some chemotactic products released during Migration in response to bacteria? | C5a, IL-8, LTB4, kallikrein, platelet-activating factor |
| Which are the main cells involved in chronic inflammation? | Macrophages, lymphocytes, and plasma cells |
| What are the most common stimuli for chronic inflammation? | Persistent infections --> Type IV hypersensitivity, autoimmune diseases, prolonged exposure to toxic agents, and foreign material |
| All the cells involved in chronic inflammation which are the most dominant? | Macrophages |
| Chronic inflammation is the result of macrophage interaction with? | T-lymphocytes |
| Which T helper cell is involved in the classical activation of inflammatory (proinflammatory)? | TH1 cells |
| Th2 cells secrete IL 4 and IL-13 --> | Macrophage alternative activation |
| What is the result of the macrophage alternative activation in the process of chronic inflammation? | Repair and anti-inflammatory |
| What is the composition of granulomas? | Composed of epithelioid cells with surrounding multinucleated giant cells and lymphocytes. |
| Granulomas are a pattern of chronic ____________. | Inflammation |
| What are epithelioid cells in granulomas? | Macrophages with abundant pink cytoplasm |
| What subtype helper T cells aid in the formation of granulomas? | Th1 cells |
| What is secreted by Th1 cells that activates macrophages, in the process of making granulomas? | INF-gamma |
| What cytokine is known to induce and maintain granuloma formation? | TNF-alpha |
| What is a possible adverse consequence of using anti-TNF drugs in a patient with a granulomatous disease? | Sequestering granulomas can break down leading to a disseminated disease |
| Why is a TB test always performed prior to starting anti-TNF therapy? | To prevent the breakdown of from granulomas in latent TB, and thus, avoid development of disseminated disease. |
| What is electrolyte condition is strongly associated with granuloma formation? | Hypercalcemia due to calcitriol production |
| What is needed on biopsy to diagnose Sarcoidosis? | Non-caseating granulomas |
| What are the most common granulomatous disease of BACTERIAL origin? | - Mycobacteria (TB, leprosy) - Bartonella henselae (cat scratch disease) - Listeria monocytogenes (granulomatosis infantiséptica) - Treponema pallidum (3 Syphylis) |
| Endemic mycoses are _____________________ diseases. | Granulomatous |
| What is a granulomatous disease due to a parasitic infection? | Schistosomiasis |
| Crohn disease si an autoinflammatory ___________________ disease. | Granulomatous |
| What foreign material ingestion (inhaled) materials are granulomatous disease? | Berylliosis, talcosis, hypersensitivity pneumonitis |
| Primary biliary cholangitis and Subacute (de Quervain) thyroiditis, are both _____________________ diseases. | Granulomatous |
| What are the two types of calcification? | Dystrophic and Metastatic calcification |
| Which type of calcification is seen in abnormal tissues? | Dystrophic |
| Dystrophic calcification extend tends to be _________________. | Localized |
| Metastatic calcification has an extend commonly described as _______________________. | Widespread |
| What are some associated conditions that exhibit dystrophic calcification? | TB (lung and pericardium) Granulomatous infections Liquefactive necrosis of chronic abscesses Fat necrosis Infarcts, thrombi, Schistosomiasis Congenital CMV, Toxoplasmosis, Rubella, Psammoma bodies CREST syndrome Atherosclerotic plaques |
| What areas are most commonly affected by metastatic calcification? | Interstitial tissues of the kidney, lung, and gastric mucosa |
| Dystrophic calcification is most likely due to: | Secondary to injury or necrosis |
| What is the etiology (reason of development) of Metastatic calcification? | Secondary to hypercalcemia or high Calcium-Phosphate product levels |
| What are some examples of high calcium-phosphate product level conditions? | CKD with secondary hyperparathyroidism, long-term dialysis, calciphylaxis, multiple myeloma |
| What is the serum calcium level of a person with evidence of dystrophic calcification? | Normocalcemic |
| Which type of calcification is seen with abnormal serum Ca2+ levels? | Metastatic calcification |
| A yellow-brown "wear and tear" pigment associated with normal aging. | Lipofuscin |
| How is Lipofuscin formed? | By oxidation and polymerization of autophagocytosed organellar membranes |
| Which organs usually show most Lipofuscin deposition upon autopsy of the elderly? | Heart, colon, liver, kidney, and eye. |
| What is the pigment usually found in during the autopsy of an elderly patient around the heart and kidneys? | Lipofuscin |
| How do free radicals cause damage to cell? | By membrane lipid peroxidation, protein modification, and DNA breakage. |
| What are ways to eliminate free radicals? | 1. Scavenging enzymes (catalase, superoxide dismutase, glutathione peroxidase) 2. Spontaneous decay 3. Antioxidants 4. Metal carrier proteins (transferrin, ceruloplasmin) |
| When does scar formation occurs? | When repair cannot be accomplished by cell regeneration alone. |
| In scar formation, the nonregulated cells, are replaced by ________________. | Connective tissue |
| What are the two types of scar formation? | Hypertrophic and Keloid |
| What collagen synthesis is increased in hypertrophic scar formation? | Type III collagen |
| Which collagen types are increased in synthesis in Keloid formation? | Type I and III collagens |
| Which type of scar formation has a much higher or significant (increased) collagen formation? | Keloid formation synthesis much more collagen |
| Hypertrophic scar has its collagen arrangement in _______________, which Keloid shows a ______________ collagen organization. | Hypertrophic ----------- parallel Keloid -------- disorganized |
| Which type of scar is confined to borders of original wound? | Hypertrophic |
| Description Of extent of keloid scar | Beyond borders of original wound with "claw-like" projection typically on earlobes, face, and upper extremities |
| Keloid formation has an increased recurrence in ethnic groups with _____________________. | Darker skin |
| What two tissue mediators solely stimulate angiogenesis? | FGF and VEGF |
| What is the role of PDGF? | 1. Induce vascular remodeling and smooth muscle migration 2. Stimulates fibroblast growth for collagen synthesis |
| What cells secrete PDGF? | Activated platelets an macrophages |
| Which tissue mediator is in charge of tissue remodeling? | Metalloproteinases |
| What is the specific role of EGF? | Stimulates cell growth via tyrosine kinases |
| What are the characteristics of Inflammatory phase of wound healing? | Clot formation, increased vessel permeability and neutrophil migration into tissue |
| What is the second phase of wound healing? | Proliferative |
| What cells are involved in the proliferative phase of wound healing? | Fibroblasts, myofibroblasts, endothelial cells, keratinocytes, and macrophages |
| What are the effector cell of the Inflammatory phase of wound healing? | Platelets, neutrophils , and macrophages |
| What are the effector cells of the Remodeling phase of wound healing? | Fibroblasts |
| What are the features of Proliferative phase of wound healing? | Deposition of granulation tissue and type III collagen, angiogenesis, epithelial cell proliferation, dissolution o clot, and wound contraction |
| What cells mediated wound contraction? | Myofibroblasts |
| What two deficiencies can delay wound healing? | Vitamin C deficiency and Copper deficiency |
| Which stage of wound healing is Type III collagen replaced by type I collagen, and incrase tensile strength of tissue? | Remodeling |
| While Vit C and copper deficiency cause delay in wound healing during the Proliferative phase, the deficiency of Zinc causes same effect in the ______________ phase of wound healing. | Remodeling |
| What enzymes break down type III collagen? | Collagenases |
| What metal (mineral) is required by Collagenases to function? | Zinc |
| Timeframe of proliferative phase of wound healing | Day 3 - weeks after wound |
| What is the common time frame for remodeling phase of wound healing? | 1 week --- 6+ months after wound |
| What is amyloidosis? | Abnormal aggregation of proteins into B-pleated linear sheets |
| What is the end result of amyloidosis? | Cellular damage and apoptosis caused by formation of insoluble fibrils |
| What is the composition of the insoluble fibrils in amyloidosis? | Abnormal aggregation of protein into B-pleated linear sheets |
| What methods and/or procedures can be used to visualize Amyloidosis? | 1. Congo red stain 2. Polarized light (apple green birefringence) 3. H&E stain |
| What is shown in a H&E stain of amyloidosis sample? | Deposits in glomerular mesangial areas and tubular basement membranes |
| What are the systemic types of amyloidosis? | Primary, Secondary, and Dialysis-related amyloidosis |
| What is the fibril protein involved in Primary amyloidosis? | AL (form Ig Light chains) |
| Which disorders are seen with primary amyloidosis? | Multiple myeloma and plasma cell disorders |
| What are the manifestations of systemic amyloidosis? | 1. Cardiac (RCM, arrhythmia) 2. GI (macroglossia, hepatomegaly) 3. Renal (nephrotic syndrome) 4. Hematologic (easy bruising, splenomegaly) 5. Neurologic (neuropathy) 6. Musculoskeletal (carpal tunnel syndrome) |
| What is the most significant Musculoskeletal manifestation of systemic amyloidosis? | Carpal Tunnel syndrome |
| What type of cardiomyopathy is seen with systemic amyloidosis? | Restrictive |
| Is nephritic or nephrotic syndrome associated with amyloidosis? | Nephrotic |
| What is defective protein in secondary amyloidosis? | Serum Amyloid A (AA) |
| What type of conditions (examples) produce secondary amyloidosis? | Rheumatoid arthritis, IBD, familial Mediterranean fever, protracted infection |
| B2-microglobulin protein defect is seen with _________________ amyloidosis. | Dialysis-related |
| What type of patients develop Dialysis-related systemic amyloidosis? | ESRD and/or long-term dialysis |
| What are examples of localized Amyloidosis? | Alzheimer disease, Type 2 DM, Medullary thyroid cancer, Isolated atrial amyloidosis, and Systemic senile amyloidosis |
| B-amyloid protein is involved in _________________ disease. | Alzheimer |
| What is the protein involved in amyloidosis in Type 2 DM? | Islet amyloid polypeptide (IAPP) |
| What is the etiology of Type 2 DM amyloidosis? | Deposition of amylin in pancreatic islets |
| What arrhythmia is more likely to develop in a patient with isolated atrial amyloidosis? | Atrial fibrillation |
| Which part of the heart is most affected in systemic senile amyloidosis? | Cardiac ventricles |
| What are the two types of hereditary amyloidosis? | Familial amyloid cardiomyopathy and Familial amyloid polyneuropathies |
| Mutated transthyretin (ATTR) causes---> | Familial amyloid cardiomyopathy and Familial amyloid polyneuropathies |
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rakomi
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