Pathophysiology chapter 5

Example of Chemotherapy:

-Adriamycin (doxorubicin) -Bleomycin -Vinblastine -Dacarbazine

Other Drugs - Examples

-Hormones -Biologic response modifiers (BRMs) -angiogenesis inhibitor drug group -Analgesics for pain control

§There are three basic mechanisms for the spread of cancer:

-Invasion -Metastasis -Seeding

Pain:

-Not usually an early symptom of cancer. -Its severity depends on the type of tumor and its location. -May be caused by: •direct pressure of the mass on sensory nerves (e.g., bone cancer). •Inflammation (irritation of nerve endings by chemical mediators). Secondary cause: infection, ischemia, and bleeding (Blood can be "irritating" to tissues and, if it collects in an area, can cause pressure on nerves).

There are two broad categories of genes that are affected by the cancerous mutations:

-Oncogenes -Tumor suppressor genes

what usually required before a normal cell will transform into a cancer cell .

-Series of several mutations to certain classes of genes (DNA) and epimutations -These mutations disrupt the balance between cell proliferation and cell death (apoptosis) leading to an abnormal and uncontrolled cell division and proliferation and therefore cancer. -Only certain mutations lead to cancer whereas the majority of mutations do not.

Examples of Malignant Cancers

-Skin Cancer (Basal Cell Carcinoma) -Brain Tumors

Spread of Malignant Tumors

-Tumors spread by one or more methods depending on the characteristics of the specific tumor cells. -They produce secondary tumors that consist of cells identical to the primary (parent) tumor.

Systemic Effects of Tumor

-Weight loss and cachexia (severe tissue wasting). -Bleeding -Anemia or decreased hemoglobin. -Severe fatigue. -Infections (such as pneumonia).

Obstruction:

-can result when a tumor compresses a duct or passageway (e.g. digestive tract) from an external position or grows inside a passageway or around a structure (Fig. 5-3). -Effect of obstruction: Restriction of Blood supply, lymphatic flow, air flow, or nerve conduction

Characteristics of Benign tumors:

-cells are: similar to normal cells, differentiated , mitosis fairly normal. -growth : relatively slow, expanding mass, frequently encapsulated. -spread: remains localized. -systemic effects: rare. -life-threatening: only in certain locations (e.g brain).

Characteristics of malignant tumors:

-cells are: varied in size and shape with large nuclei, many undifferentiated, mitosis increased and atypical. -growth: rapid growth, cells not adhesive, infiltrate tissue, no capsule. -spread: invades nearby tissue or metastasize to distant sites through blood and lymph vessels. -systemic effects: often present. -life-threatening: yes, by tissue destruction and spread of tumors.

WARNING SIGNS OF CANCER

1 . Unusual bleeding or discharge anywhere in the body. 2. Change in bowel or bladder habits (e.g., prolonged diarrhea or discomfort). 3. A change in a wart or mole (i.e., color, size, or shape). 4. A sore that does not heal (on the skin or in the mouth, anywhere). 5. Unexplained weight loss. 6. Anemia or low hemoglobin, and persistent fatigue. 7. Persistent cough or hoarseness without reason. 8. A solid lump, often painless, in the breast or testes or anywhere on the body. Even if cancer is not present, any of these signs could be the indicator of some other disease process, so it should be checked by a physician. A critical observation can save a life. Sometimes a client may need encouragement to have such warning signs investigated.

"Seven Steps to Heath" to prevent disease:

1- Be a nonsmoker and avoid second-hand smoke. 2- Eat 5 to 10 servings of vegetables and fruit a day. Choose high-fiber, lower-fat foods. If you drink alcohol, limit your intake to one to two drinks a day 3- Be physically active on a regular basis: this will also help you maintain a healthy body weight. 4- Protect yourself and your family from the sun. 5- Follow cancer screening guidelines. 6- Visit your doctor or dentist if you notice any change in your normal state of health. 7- Follow health and safety instructions at home and at work when using, strong, and disposing of hazardous materials.

Adverse effects of Radiation depend on the dose and extent of penetration of radiation into the body:

1. Bone marrow depression → body defenses are reduced. 2. Epithelial cell damage includes damage to blood vessels (vasculitis) and skin inflammation (as in a sunburn), and hair loss (alopecia) occurs. 3. Damage of the digestive tract mucosa (inflammation & ulceration), resulting in some nausea, vomiting, and diarrhea, a risk of malnutrition and dehydration, melena or hematemesis (blood in the stool or vomitus), etc. 4. Sterility or a risk of teratogenesis (congenital malformations in embryo or fetus): damage of the ovaries or testes by radiation (Sperm banking or egg retrieval and storage should be discussed with the patient before starting treatment). 5. fatigue and lethargy (lack of energy and enthusiasm) accompanied by mental depression.

The stages in carcinogenesis:

1. Exposure to a single or a combination of initiating factors or pro-carcinogens causes first irreversible changes in the cell DNA 2. Development of a malignant Tumor 3. Spread of the malignant cells

types of tests used for the diagnosis of cancer:

1.Blood tests 2.Tumor markers 3. X-ray, ultrasound, magnetic resonance imaging (MRI), and computed tomography (CT) scans 4. Cytologic tests

Chemotherapy - Examples of Adverse Effects (side effects)

As with radiation, the normal cells are also damaged, most commonly the skin and mucosa, bone marrow, and gonads • Bone marrow depression: dangerously low blood counts, hemorrhage as a major risk with thrombocytopenia. • Infections • Vomiting owing to direct chemical stimulation by the drug of the emetic or vomiting center in the brain (Antiemetic drugs may be helpful in decreasing vomiting) • Damage of the epithelial cells : Hair loss (alopecia), skin and mucosa breakdown, etc. Notes: Not all cancer cells are sensitive to radiation or chemotherapy

Infection:

Caused by tissue necrosis, ulceration, and reduction of host resistance

A cancer treatment may be:

Curative Palliative

Development of a malignant Tumor

Later Exposure to promoters (e.g. hormones, environmental chemicals, etc.) causes further changes in DNA, resulting in less differentiation and an increased rate of mitosis → Malignant Tumor development (Some tumors develop relatively rapidly, whereas others require decades to develop). -The expanding mass compresses nearby blood vessels, leading to necrosis (&infection) and an area of inflammation around the tumor, and increases pressure on surrounding structures. -Some cancer cells secrete growth factors, which stimulate angiogenesis (the development of new capillaries in the tumor), thus promoting tumor development. (Note: several new Anti-angiogenesis drugs are based on this blocking action. But these drugs are of limited effect in patients receiving chemotherapy because the reduction in blood vessel development impairs the delivery of chemotherapy agents to the tumor). -Tumor cells may increase the uptake of nutrients or "trap" nutrients, depriving normal cells and preventing any tissue regeneration.

Metastatic adenocarcinoma in LN

Lymph node with metastasis (arrow) Carcinomas spread primarily by lymphatics leading to enlargement of the lymph nodes.

Transcoelomic spread

Neoplasms can spread by seeding within body cavities such as the pleural cavity or peritoneal cavity. This pattern of spread is more typical for carcinomas than other neoplasms

Infections (such as pneumonia):

Occur as host resistance declines.

Carcinogenesis

Pathophysiology of Cancer

Paraneoplastic syndromes are

additional problems associated with certain tumors because tumor cells release substances that affect neurologic function or blood clotting or have hormonal effects.

Why Many neoplasms (tumors) are unable to function as normal tissue cells

because they consist of atypical (abnormal) or immature cells.

Bleomycin:

also an antitumor antibiotic that inhibits DNA synthesis

Carcinogenesis

also called oncogenesis or tumorigenesis, is the process that leads to the formation of a cancer, whereby normal cells are transformed into cancerous cells that form a tumor and can spread.

Dacarbazine:

an alkylating agent nonspecific drug

Adriamycin (doxorubicin):

an antitumor antibiotic that binds DNA and inhibits synthesis of nucleic acids

Tumor suppressor genes:

are genes that inhibit cell division, survival, or other properties of cancer cells. Tumor suppressor genes are often disabled by cancer-promoting genetic changes.

why It is difficult to establish precise predisposing or causative (etiologic) factors for each cancer

because it takes many years to gather sufficient documentation, and frequently multiple factors are involved. But some specific cancers have well-established risk factors (e.g., bronchogenic carcinoma or lung cancer and cigarette smoking).

Why A diagnostic test is not usually 100% reliable by itself

because there may be false-negative or false-positive results.

Weight loss and cachexia (severe tissue wasting):

caused by anorexia, fatigue, pain, stress, nutrient trapping by reproducing tumor cells, etc.

Severe fatigue

caused by cachexia, anemia, stress, etc.

the root of malignant transformation are

changes in DNA.

The staging system describes the

extent of the disease at the time and therefore provides a basis for treatment and prognosis.

In order for a normal cell to transform into a cancer cell:

genes that regulate cell division, growth, apoptosis, differentiation, and DNA repair must be mutated (altered).

Palliative

if the cancer is advanced (Palliative treatment is intended to reduce the manifestations and complications related to the cancer and to prolong life). For example decreasing the size of a tumor may lessen the pressure on a nerve, relieving pain, or reduce pressure on the esophagus or bronchus).

Curative

if the tumor is small and localized able to heal or cure

Staging of cancer

is a classification process applied to a specific malignant tumor at the time of diagnosis.

anorexia

lack or loss of appetite for food

Exposure to a single or a combination of initiating factors or pro-carcinogens causes first irreversible changes in the cell DNA

leading to transformation of the normal cell into a malignant cell. This initial change does not create an active neoplasm.

Oncogenes:

may be normal genes that are expressed at inappropriately high levels, or altered genes that have novel properties. In either case, expression of these genes promotes the malignant phenotype of cancer cells. (A proto-oncogene: A normal gene which, when altered by mutation, becomes an oncogene that can contribute to cancer).

ulcer

open sore or lesion in the skin or mucous membrane

Local Effects of Tumor

pain, infection, obstruction

An alternative to surgery for small single tumors in the lungs or liver is

radiofrequency ablation (RFA) (less invasive) (where heat is supplied in the form of radio waves to destroy the malignant cells and tissue immediately surrounding the tumor).

Spread of the malignant cells

result in cells that are capable of detaching from the tumor and spreading to distant sites.

Anemia or decreased hemoglobin:

resulting from anorexia, chronic bleeding with iron loss, etc.

X-ray, ultrasound, magnetic resonance imaging (MRI), and computed tomography (CT)

scans are methods of examining changes in tissues or organs.

Radiation may also be used before surgery to

shrink a tumor or destroy loose surface cells, or may be begun after healing of the surgical site.

Liver metastasis

tan-white masses , multiple and irregularly sized. The primary tumor is commonly in the Gastrointestinal tract (colon- stomach)

Histologic and Cytologic

tests are the only dependable confirmation of malignancy.

Oncology is

the study of malignant tumors (otherwise known as cancer).

Bleeding:

the tumor cells may erode the blood vessels or cause tissue ulceration (Chronic blood loss leads to iron deficiency anemia)

Vinblastine:

§a cell-cycle-specific antimitotic drug

A neoplasm or tumor

§a cellular growth that is no longer responding to normal body controls.

Tumor markers

§are substances, enzymes, antigens, or hormones, produced by some malignant cells and circulating in the blood or other body fluid. Examples of tumor markers: human chorionic gonadotropin (hCG) for testicular cancer, alpha-fetoprotein (AFP) for hepatocellular cancer, prostate specific antigen (PSA) for prostate cancer. Note: Many of these substances are present with other diseases; therefore their presence is not diagnostic by itself.

What The only definitive test for malignancy requires?

§examination of the tumor cells themselves.

Surgery

§involves the removal of the tumor and surrounding tissue, including the nearby lymph nodes if required (but in some cases, removal of adequate surrounding tissue may result in considerable impact on function, e.g., in the brain). -Sometimes complete removal of the tumor may be impossible, but reducing the size of the mass may prevent complications and alleviate some symptoms.

adjuvant therapy

§is additional prophylactic treatment used in cancers that are known to metastasize early in their development, producing secondary tumors that are too small to be detected (micrometastases). For example, following apparent complete removal of a localized breast tumor with no evidence of spread, chemotherapy and radiation may be administered as a precaution in case a few cancer cells have broken away to a lymph node or adjacent tissue.

Radiation

§may be used alone or combined with other therapies to treat radiosensitive tumors.

Radiotherapy causes

§mutations or alterations in the targeted DNA, thus preventing mitosis or causing immediate cell death. Radiation also damages blood vessels, cutting off blood supply to the tumor cells and starving them. -Some types of cancer are radio-resistant or unresponsive to radiation.

Metastasis

• means spread to distant sites by blood or lymphatic channels. In this case the tumor cells erode into a vein or lymphatic vessel, travel through the body, and eventually lodge in a hospitable environment to reproduce and create one or more secondary tumors. •Frequently the first metastasis appears in the regional lymph nodes, which localize the tumor cells for a time. •These lymph nodes are checked at the time of surgery, and often several are removed. •Note: Usually the lymph nodes are removed or treated to eradicate any micrometastases that may be missed, particularly in cancers that are known to spread at an early stage (e.g., breast cancer).

Seeding

• refers to the spread of cancer cells in body fluids or along membranes, usually in body cavities •Again, the tumor cells break away and travel easily with the movement of fluid and tissue. Example: ovarian cancer

Chemotherapy

•Chemotherapy may be used alone, or may be combined with surgery or radiation. •The classifications include antimitotics, antimetabolites, alkylating agents, and antibiotics. •The drugs interfere with protein synthesis and DNA replication at different points in the tumor cell cycle, thus destroying the cells. •Some types of cancer cells respond well to chemotherapy, whereas other types of cells are resistant to this therapy.

Causes that lead to mutations (examples) and therefore cancer :

•Environmental factors, chemicals (carcinogens) •Radiation •Diet •Hormones •Oncogenic viruses •Age •Chronic irritation and inflammation •Random mistakes in normal DNA replication. •Temporary or long-term immunodeficiency •Genetic factors: Variants of inherited genes (oncogenes) may also predispose individuals to cancer.

Basic treatment measures are:

•Surgery •Chemotherapy •Immunotherapy (stimulates the patient's immune system to target the cancer and attack it, or radiation) •Radiation • or a combination, depending on the specific cancer.

Tumors are named according to a system

•The root word: is the cell of origin - such as cerebro for brain. •The suffix "oma" that indicates a benign or malignant tumor. •The suffix "carcinoma" that indicates malignant tumors for epithelial tissue •The suffix "sarcoma" that indicates malignant tumors for connective tissue. However, a number of neoplastic disorders have acquired unique names (e.g., Hodgkin disease, Wilms tumor, and leukemia).

Blood Tests

•are important both as an indicator of a problem and in monitoring the effects of chemotherapy and radiation. •Hemoglobin and erythrocyte counts may be low, a general sign of cancer. •Therapy frequently results in thrombocytopenia, erythrocytopenia, and leukopenia, and these may limit treatment if cell counts fall too low.

Tests are important in:

•early detection of cancer •long-term monitoring of the patient subsequent to the diagnosis. Note: Routine screening tests and self-examination programs need to be promoted, especially in high-risk patients.

Invasion

•refers to local spread, in which the tumor cells grow into adjacent tissue & destroy normal cells.