Porth's Essentials of Pathophysiology, 4e

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Cell and Tissue Function

U N I T 1

Local and Regional Manifestations Because tumor cells replace normally functioning paren- chymal cells, the initial manifestations of cancer usually reflect the function of the primary site of involvement. For example, lung cancer initially produces impairment of respiratory function; as the tumor grows and metas- tasizes, other body structures become affected. Cancer has no regard for normal anatomic bound- aries; as it grows, it invades and compresses adjacent structures. Abdominal cancer, for example, may com- press the viscera and cause bowel obstruction. Growing tumors may also compress and erode blood vessels, causing ulceration and necrosis along with frank bleed- ing and sometimes hemorrhage. The development of effusions (i.e., fluid) in the pleu- ral, pericardial, or peritoneal spaces may be the present- ing sign of some tumors. Direct involvement of the serous surface seems to be the most significant inciting factor, although many other mechanisms such as obstruction of lymphatic flow may play a role. Most persons with pleu- ral effusions are symptomatic at presentation with chest pain, shortness of breath, and cough. More than any other malignant neoplasms, ovarian cancers are asso- ciated with the accumulation of fluid in the peritoneal cavity. Complaints of abdominal discomfort, swelling and a feeling of heaviness, and increase in abdominal girth, which reflect the presence of peritoneal effusions or ascites, are the most common presenting symptoms in ovarian cancer, occurring in up to 65% of women with the disease. 33 Systemic Manifestations Cancer also produces systemic manifestations such as anemia, anorexia and cachexia, and fatigue and sleep dis- orders. Many of these manifestations are compounded by the side effects of methods used to treat the disease. In its late stages, cancer often causes pain (see Chapter 35). Pain is probably one of the most dreaded aspects of can- cer, and pain management is one of the major treatment concerns for persons with incurable cancers. Although research has produced amazing insights into the causes and cures for cancer, only recently have efforts focused on the associated side effects of the disease. Anemia Anemia is common in persons with various types of cancers. It may be related to blood loss, iron deficiency, hemolysis, impaired red cell production, or treatment effects. 34–36 For example, drugs used in treatment of cancer are cytotoxic and can decrease red blood cell production. Also, there are many mechanisms through which erythrocyte production can be impaired in persons with malignancies including nutritional defi- ciencies, bone marrow failure, a blunted erythro- poietin response to hypoxia, and an iron deficiency. Inflammatory cytokines generated in response to tumors decrease erythropoietin synthesis, resulting in a decrease in erythrocyte production. Iron deficiency may

(HTLV-1) is the only known retrovirus to cause cancer in humans. Human T-cell leukemia virus-1 is associated with a form of T-cell leukemia that is endemic in certain parts of Japan and some areas of the Caribbean and Africa, and is found sporadically elsewhere, including the United States and Europe. 2 Similar to the AIDS virus, HTLV-1 is attracted to the CD4 + T cells, and this subset of T cells is therefore the major target for malignant transformation. The virus requires transmission of infected T cells by way of sexual intercourse, infected blood, or breast milk.

SUMMARY CONCEPTS

■■ The etiology of cancer is highly complex, encompassing both molecular and cellular origins, and external and contextual factors such as heredity and environmental agents that influence its inception and growth. It is likely that multiple factors interact at the molecular and cellular level to transform normal cells into cancer cells. ■■ The molecular pathogenesis of cancer is thought to have its origin in genetic damage or a mutation that changes the cell’s physiology and transforms it into a cancer cell.The types of genes involved in cancer are numerous, but two main groups are the proto-oncogenes, which control cell growth and replication, and tumor- suppressor genes, which are growth-inhibiting regulatory genes. ■■ Genetic and molecular mechanisms that increase susceptibility to cancer and/or facilitate cancer include defects in DNA repair mechanisms, defects in growth factor signaling pathways, evasion of apoptosis, development of sustained angiogenesis, invasion, and metastasis. Genetic and epigenetic damage may be the result of interactions between multiple risk factors or repeated exposure to a single carcinogenic (cancer-producing) agent. ■■ Among the external and contextual risk factors that have been linked to cancer are heredity, hormonal factors, obesity, immunologic mechanisms, and environmental agents such as chemicals, radiation, and cancer-causing viruses and microbes.

Clinical Manifestations There probably is not a single body function left unaf- fected by the presence of cancer. Even the presenting signs and symptoms may be localized or widespread.

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