Applied Pathophysiology: A Conceptual Approach to the Mechanisms of Disease Lecture Notes PDF

Lecture Material is adapted from © 2022 Wolters Kluwer Health, Lippincott Williams & Wilkins Applied Pathophysiology: A Conceptual Approach to the Mechanisms of Disease Chapter 7: Altered Cellular Proliferation and Differentiation Module 2: The Impact of Cancer on Tissues, Organs and Organ Systems...

Lecture Material is adapted from © 2022 Wolters Kluwer Health, Lippincott Williams & Wilkins Applied Pathophysiology: A Conceptual Approach to the Mechanisms of Disease Chapter 7: Altered Cellular Proliferation and Differentiation Module 2: The Impact of Cancer on Tissues, Organs and Organ Systems Dr. Romeo Batacan Jr. MPAT12001 Medical Pathophysiology Lecture Series Copyright © 2017 Wolters Kluwer Health | Lippincott Williams &Wilkins Altered Cell Proliferation and Differentiation Normal cells: cellular proliferation and differentiation is under the control of genes Neoplastic cells ignore genetic controls resulting in: AUTONOMY: Unregulated cellular proliferation ANAPLASIA: Loss of cellular differentiation, therefore loss of cell function The greater the degree of anaplasia, the more aggressive or malignant the tumor will be Altered Cell Proliferation and Differentiation 1. Loss of cell‐to‐cell communication Further unrestricted growth of tumor cells 2. Increased energy expenditure Deprives unaffected cells of nutrients 3. Increased motility and loss of cohesion/adhesion Promoting movement to other locations 4. Rapid angiogenesis Provide extensive blood flow to tumor cells 5. Substance secretion Altering metabolism and degrading neighboring unaffected cells 6. Foreign antigen presentation on cancer cell surface Triggering immune response  Benign versus Malignant Tumors remain localized, resemble tissue of origin: benign Overproliferate, but differentiated Nowak T, Handford AG. Pathophysiology: Concepts and Applications for Health Care Professionals. They can still be dangerous: tumor growth impinge nearby 3rd ed. New York, McGraw‐Hill; 2004 structures, obstruct vital functions: can lead to death Invasive, destructive, rapidly proliferating tumors: malignant Promote ischemia, necrosis Cancer: malignant neoplasm Characteristic Benign Malignant 1. Cell structure Near normal Abnormal shapes, larger cells and nucleus 2. Tissue structure Orderly Disordered, irregular 3. Growth rate Above normal Rapid 4. Invasive growth Uncommon Typical 5. Metastasis Never Typical 6. Capsule Typical Rare, incomplete of present 7. Anaplasia Minimal Typical 8. Prognosis Good Poor Cancer Spread 1. Local spread: proliferation of the neoplasm within the tissue of origin 2. Direct extension: tumor cells are moving into adjacent tissue and organs 3. Seeding: form of direct extension, implantation of cancer cells in body cavities 4. Metastasis: neoplasms are spread to distant sites Mechanisms: Metastasis via embolism (main mechanism) Metastasis via body cavities (seeding) Iatrogenic metastasis (due to medical intervention) Cancer Spread Nowak T, Handford AG. Pathophysiology: Concepts and Applications for Health Care Professionals. 3rd ed. New York, McGraw‐Hill; 2004 Cancer Spread Neoplasms preferred location tend to be predictable Tropism: the affinity of the primary tumor to a specific distant site Factors promoting preferential location: 1. Favorable environment offered by the new tissue or organ 2. Adherence molecule compatibility between the neoplasm and the new tissue 3. Location of the organ in relation to the path of blood flow McCance KL, Huether S. Pathophysiology. 7th ed. N.S.W, Mosby; 2015 Metastasis C F D E B McCance KL, Huether S. Pathophysiology. 7th ed. N.S.W, Mosby; 2015 Cancer Nomenclature Tumor identification is commonly based on the tissue of origin Most benign tumor: tissue of origin + “oma” Most malignant tumor: Tissue of origin+ “carcin” + oma Tissue of origin+ “sarc” + oma There are many exceptions Lymphoma, melanoma, leukemia etc. Carcinoma in situ: Carcinoma is confined to the epithelium Not penetrated the basement membrane Asymptomatic, favourable prognosis Cancer Classifications: TNM staging T: tumor Classifying the extent or spread of neoplasm N: node (usually applied to solid tumors) M: metastasis Tumor size Lymph node involvement Location/metastasis Higher number, more extensive tumor size and involvement Cancer Classifications: TNM staging Treatment decisions are often based on staging criteria: more invasive require more aggressive therapy T1N0M0 T2N1M0 T3N2M1 Nowak T, Handford AG. Pathophysiology: Concepts and Applications for Health Care Professionals. 3rd ed. New York, McGraw‐Hill; 2004 Cancer Classifications: Grading The process of differentiating the level of anaplasia (loss of cell differentiation) depicted by the tumor I (well differentiated, resemble tissue of origin most) II, III, IV (highly undifferentiated, little resemblance) Higher numeric staging: Increased size of tumor Local to distant invasion Cancer Prognosis Nowak T, Handford AG. Pathophysiology: Concepts and Applications for Health Care Professionals. Many factors affect outcome and course 3rd ed. New York, McGraw‐Hill; 2004 Type of cancer Location Stage Person’s age Overall health Response to treatment 5 year survival rate: % of people who are living 5 year after diagnosis Includes who are cancer free Includes remission Living with cancer Clinical Manifestations of Cancer Early general manifestations are often vague Major related manifestations are related: 1. Systemic inflammatory and immune response: lymphadenopathy, unexplained fever, anorexia, cachexia 2. Increased metabolic rate induced by tumors 3. Systemic effects of the neoplasm unrelated to cancer (Paraneoplastic syndromes) 4. Local effects of tumor encroachment or obstruction on neighboring tissues 5. Effects on blood Paraneoplastic Syndromes Hormonal/Neurologic/Hematologic/Chemical disturbances that are not directly related to invasion by the primary tumor Responsible for wide range of clinical manifestations Common characteristics of neoplasms that cause paraneoplastic syndromes: Ability to produce and secrete ectopic hormones Mimic hormone function: clinical manifestation of oversecretion of that hormone Disturb neurologic function Diagnostic Tests History taking and physical examination Imaging studies Direct visualization of tumor masses X‐rays/endoscopy/CT/MRI/ultrasound Biopsy and cytology studies Tumor has been located Marieb EN, Hoehn KN. Human Anatomy & Physiology. 9th ed. Boston, Pearson Education; 2013 Tissue samples (biopsy) Cells examined (cytology) Presence and stage of neoplasm Most cancer: definitive diagnosis only with microscopic examination of tumor cells Tumor markers Other blood, urine and tissue tests Diagnostic tests: tumor markers Produced by the tumor itself or by unaffected cells in response to the presence of tumor Tumor markers are used to: 1. main role: observe clinical course of cancer after diagnosis (treatment effectiveness) 2. screen and identify individuals at high risk for cancer 3. diagnose specific types of tumors Cancer Treatment 1. Completely eradicate neoplasms 2. Control continued growth 3. Reduce symptoms without curing the cancer Major treatment strategies: Surgery/Chemotherapy/Radiation/Hormone/Immunotherapy Alone or combination Treatment of cancer involves psychosocial care Patient, family (anxiety, depression) Holistic approach Alternative, complementary, experimental therapies Palliative care: treating symptoms without curing the cancer Adverse effects of cancer treatment Cancer Prevention Being aware of known carcinogens (The hateful 13!) Avoiding what you can, many types of cancer are considered preventable McCance KL, Huether S. Pathophysiology. 7th ed. N.S.W, Mosby; 2015 Cancer screening Cervical cancer screening program Breast cancer (mammography) Cervical cancer (Pap smear) Colorectal cancer (rectal examination, fecal occult blood test, colonoscopy) Prostate cancer (PSA testing, transrectal ultrasonography) Melanoma (self‐examination) Early detection No associated symptoms Craft AJ, Gordon C, Tiziani A. Understanding pathophysiology. 1st ed. Chatswood, Mosby; 2011 Reduced incidence