Disturbances in Cellular Functioning

ONCOLOGY
CANCER A disease process that begins when an abnormal cell is transformed by the genetic mutation of the cellular DNA. ONCOLOGY refers to the medical specialty that deals with the diagnosis, treatment and study of cancer. REVIEW OF SYSTEMS HEMATOLYMPHATIC SYSTEM Involves: 1. Blood and Bone Marrow 2. Reticuloendothelial System (RES) 3. Lymphatic glands/organs 4. Immune System

A. HEMATOLOGIC SYSTEM BONE MARROW - site of HEMATOPOIESIS production of blood. - As child ages, marrow activity decreases. - By adulthood, marrow activity is limited to: > Pelvis site of Bone Marrow Transplant > Ribs > Vertebra > Sternum > Femur BLOOD a type of connective tissue that consists of cells and cell fragments and by a liquid matrix called PLASMA. FORMED ELEMENTS - RBC (Erythrocytes) - WBC (Leukocytes) - Platelets (Thrombocytes)

STEM CELLS -Single population of cells that differentiate to give rise to the formed elements of blood.
STEM CELLS Lymphoblast

Proteoblast

Megakaryoblast Monoblast

Myeloblast RBC

Lymphocyte Basophils Eosinophils Neutrophils Monocyte

Platelets

Granulocytes

Agranulocytes WBC

B. RETICULOENDOTHELIAL SYSTEM - Composed of MACROPHAGES which arises from Monocytic cells. MACROPHAGES phagocytize bacteria, dead cells, cell fragments and any other debris within the tissues. Functions: 1. Defend 2. Remove dead cells or toxins 3.Stimulate other lymphoid tissue 4. Give rise to KUPFFER CELLS macrophages in the liver. DUST CELLS lungs Found in the: - Spleen - Liver - Lungs - Lymphoid organs

C. LYMPHATIC SYSTEM Organs: 1. TONSILS a. Palatine Tonsils located on each side of the posterior opening of the oral cavity. b. Pharyngeal / Adenoid Tonsils - Near internal opening of the nasal cavity. c. Lingual Tonsil posterior surface of the tongue. 2. LYMPH NODES filters Lymph. - Distributed along the various lymphatic vessels and most lymph passes through at least one lymph node before entering the blood. LYMPH fluid that enters the Lymphatic capillaries, it passes through the lymphatic vessels to return to the blood. Types: Inguinal Nodes groin Axillary nodes armpits Cervical Nodes neck

3. SPLEEN filters blood instead of lymph. - detect and respond to foreign substances in the blood and destroy worn out RBC. 4. THYMUS Located in the posterior mediastinum, the partition dividing the thoracic cavity into right and left parts. - Site for production and maturation of lymphocytes. D. CELLS Functions: 1. Basic unit of life 2. Transport of Oxygen and nutrients. 3. Production of ATP. 4. Protection and support Bone cells 5. Movement muscle cells 6. Communication nerve cells 7. Inheritance

Parts: A. PLASMA MEMBRANE aid in transport of substances in and out of the cell. B. CYTOPLASM 1. Organelles Little organs a. Mitochondria ATP synthesis. b. Endoplasmic Reticulum RNA synthesis. c. Ribosomes Protein synthesis d. Golgi Apparatus Lysosomes production e. Lysosomes contains hydrolytic enzymes that repairs worn out cells. f. Centrosomes organize a complex of centrioles and microtubules which support cytoplasm and help in the movement of substances or organelles within the cytoplasm. 2. Cytosol (Fluid Medium) Intracellular Fluid (IFC) refers to the cytosol inside the cell and fluid inside the nucleus called Nucleoplasm. C. NUCLEUS control center of the cell. a. Nuclear Envelope surrounds the nucleous. b. Nucleolus site of ribosome formation. c. Chromatin Fibers involve in mitosis. MITOSIS somatic reproduction of cells.

INTERPHASE

PROPASE Chromatin condenses into chromosomes which is composed of 2 Chromatids joined at the centromere.

METAPHASE chromosomes align in the center of the cell.

ANAPHASE chromatids separate to form 2 sets of identical chromosomes.

TELOPHASE chromosomes disperse, nuclear envelopes and nucleoli form, cytoplasm divides.

MITOSIS Complete

E. IMMUNE SYSTEM IMMUNITY the ability to resist damage from foreign substances, such as microorganisms and harmful chemicals. Types of Immunity: 1. INNATE IMMUNITY a. Mechanical Mechanisms prevent the entry of microorganisms. a.1. Skin and mucous membranes. a.2. Tears, saliva, urine wash microorganisms from the surface of the body. b. Chemical Mediators Complement promote inflammation and phagocytosis and can directly lyse (rupture) bacterial cells. Interferons Protect the body against viral infection. -Because some cancers are induced by viruses, interferons may play a role in controlling cancers by activating macrophages and Natral Killer cells which attack tumor cells. Histamine, Prostagladins, Leukotrienes - Promote inflammation.

c. White Blood Cells Neutrophils first cells to enter infected tissues. Macrophages are monocytes that leave the blood, enter infected tissues and enlarge about fivefolds. Basophils motile WBC, promote inflammation. Mast cells non motile cells, promote inflammation. Natural Killer cells - type of lymphocyte produced in red bone marrow, recognize classes of cells, such as tumor cells or viral infected cells. d. Inflammatory Response 2. ADAPTIVE IMMUNITY - Involves activities of LYMPHOCYTES. Antigens substances that stimulate adaptive immune system. LYMPHOCYTES responsible for the destruction of antigens. a. T Cells released from the thymus. b. B cells released from the bone marrow.

a. ANTIBODY MEDIATED IMMUNITY - Exposure of the body to an antigen can result in the activation of B cells and the production of Antibodies which destroy the antigens. ANTIBODIES found in body fluids, proteins produced in response to antigens. IgG cross the placenta, provide protection to the fetus and newborn. IgM first antibody produced. IgA Found in colostrums and milk, provide protection to the newborn. IgE IgD b. CELL MEDIATED IMMUNITY - Is the function of cytotoxic T Cells and is most effective against microorganisms that live inside the cells. - Essential for fighting viral infections and attacking tumors.

ACQUIRED ADAPTIVE IMMUNITY 1. ACTIVE NATURAL antigens are introduced through natural exposure. Ex. Chicken pox 2. ACTIVE ARTIFICIAL vaccines. 3. PASSIVE NATURAL Ex. IgG placenta IgA breast milk/colostrum 4. PASSIVE ARTIFICIAL antibodies produced by another person or an animal are injected. Ex. Antiserum

CANCER
NEOPLASIA neo = new plasia = molding - Unresponsive cell growth unresponsive to normal growth control mechanism. NEOPLASM group of abnormal cells that can be: Benign or Malignant METASTASIS hallmark of malignant neoplasm Meta beyond stasis Standing - Spread of cancer cells from the primary tumor to distant sites.

ETIOLOGY
D IET fats, salt cured, smoked meat, foods containing nitrates and nitrites. OBESITY associated with endometrial cancer and post menopausal breast cancer. R ADIATION Sunlight, radiation therapy, x-rays. P HARMA Diethylstilbestrol (DES) used to prevent miscarriage, may cause Adenocarcinoma (Vaginal cancer) Oral contraceptives & estrogen Replacement therapy linked to hepatocellular, endometrial and breast cancers. O CCUPATIONAL / INDUSTRIAL asbestos and pesticide G ENETICS BRCA 1 gene linked to ovarian and breast cancer. BRCA 2 gene (Breast Related Cancer) early onset breast cancer.

I NFECTIOUS AGENTS Viruses and bacteria VIRUSES are thought to incorporate themselves in the genetic structure of that cell, thus altering future generations of that cell population. Herpes simplex virus, cytomegalovirus, Human papilloma virus cervical CA HIV Kaposis Sarcoma Helicobacter pylori gastric CA Epstein Barr Virus hodgkins disease A LCOHOL synergistic effect to smoking. T OBACCO SMOKE the single most lethal chemical carcinogen, accounts for at least 30% of Cancer deaths. - Strongly associated with lung, head and neck, esophagus, pancreatic, cervical and bladder cancer. Tobacco Chewing oral cancer E NDOGENOUS HORMONES Estrogen proliferation of breast cancer

PATHOPHYSIOLOGY OF THE MALIGNANT process

CARCINOGENESIS -Also called Malignant Transformation. -A process through which normal cells are transformed into malignant or cancer cells. Stages: 1.INITIATION - Carcinogens (intiators) damages DNA. - initial exposure to antigens. - Alteration of genetic structure of the cells. - damage may lead to genetic mutations if not repaired. - DNA DAMAGE 2. PROMOTION - additional assaults to the cells. - repeated exposure to carcinogens resulting in Malignant Conversion =Mutated genes. - GENETIC DAMAGE

3. PROGRESSION - Cells are increasingly malignant in appearance and behavior and develop into an invasive cancer that metastases to distant body parts. - MALIGNANT CELLS INVASION refers to the growth of the primary tumor into the surrounding host tissues. METASTASIS is the dissemination or spread of malignant cells from the primary tumor to distant sites by direct spread of tumor cells to body cavities or through lymphatic and blood circulation. MALIGNANT CELLS can invade and metastasize because of 3 reasons: 1.Mechanical pressure exerted by rapidly proliferating neoplasms may force fingerlike projections of tumor cells into surrounding tissues and interstitial spaces.

2. They possess or produce specific destructive enzymes that destroy surrounding tissues facilitating invasion. Protinases (enzymes) Collagenases specific to collagen. Plasminogen Activators Plasma Lysosomal Hydrolyses 3. Less adherent and may break off from the primary tumor and invade adjacent structures. METASTATIC MECHANISMS LYMPH & BLOOD Key mechanisms by which cancer cells spread. LYMPHATIC SPREAD -Is the most common mechanism of metastasis. -Tumor emboli enter the lymphatic channels by way of the interstitial fluid that communicates with lymphatic fluid. -After entering the lymphatic circulation, malignant cells either lodge in lymph nodes or pass between lymphatic and venous circulation.

BREAST TUMOR frequently metastasize in this manner through axillary, clavicular, and thoracic lymph channels. 2. HEMATOGENOUS SPREAD -Malignant cells are dessiminated through the blood stream. 3. ANGIOGENESIS -Malignant cells induce the growth of new capillaries from the host tissue to meet their needs for nutrients and oxygen. -Through this vascular network, tumor emboli can enter the systemic circulation and travel to distant sites.

CANCER DEVELOPMENT
A. PROLIFERATION -A process of CELL RENEWAL Forms: 1. HYPERPLASIA increase in number of cells thereby increasing its size. 2. METAPLASIA conversion or transformation of one mature type of cell into another different cell type. 3. DYSPLASIA a normal or unusual change of cell in size, shape and arrangement. 4. ANAPLASIA growth resulting to poorly differentiated cells. Most indicative of Malignancy. 5.NEOPLASIA uncontrolled cell growth not based on physiologic demand. B. DIFFERENTIATION - Cells DIVERSIFY - Become more complex in arrangement and behavior.

NEOPLASTIC TRANSFORMATION NORMAL CELL CHARACTERISTICS CELL CYCLE - Controlled to maintain the normal number of cells in the body. - Cells that die are replaced but no extra cells are produced. Gap 2
Protein and RNA synthesis

Synthesis
DNA synthesis and replication

Mitosis
DEATH

Gap 1
Production of enzymes for DNA synthesis

Gap 0
Resting phase

Cellular Proto oncogenes - present in cellsand act as an on switch for cellular growth. Tumor Suppressor genes - turn off or regulate unneeded cellular proliferation. DIFFERENTIATION Cell specialized as they mature. CONTACT INHIBITION cells spread freely about a medium until they contact another cell. NEOPLASTIC CELL CHARACTERISTICS 1. ALTERED CELL CYCLE - Cancer cells do not go through the cell cycle at a faster rate tha normal cells, rather, the abnormality is that they do not stop replicating due to: a. Lack of responses to signals to stop replicating. b. Lack of responses to cell death APOPTOSIS.

2. ALTERED DIFFERENTIATION a. Appearance - Normal cells have well organized cellular components, while CA cells have variable sizes and shapes. - CA cells have abnormal number and arrangement of chromosomes. - Well differentiated cells are mature in appearance and more like the normal cells. - Undifferentiated cells ANAPLASTIC CELLS appear disorganized and have no resemblance to the tissue of origin. b. Cell Membrane loss of glycoproteins results in loss of cellular adhesion and communication. - loss of antigens that identify the cell as self. c. Tumor Specific Antigen - Tumors express more of an antigen than is expressed by normal cells. - can be used as a diagnostic tool in the detection of cancer or in monitoring the effectiveness of CA treatment.

d. Function CA cells do not function normally and may even act in a way that causes damage to the host. 3. ALTERED GROWTH CHARACTERISTICS a. CONTACT INHIBITION - Cancer cells continue to spread even when they are already in contact with another cell. b. DOUBLING TIME - Time required for cancer cells to double its mass/size. - It may take 10 years for a tumor to reach 1 cm. In only 1 year the same tumor may grow to 8 cm. - Rate: 1, 2, 4, 8, 16, 32 - 1 cm. = tumor is clinically evident. 4. GENETIC CHANGES Pro-oncogenes (+) effect on cell growth Tumor Suppressor genes ( - ) effect on cell growth

Stress, carcinogens, genetics

Activate Pro-oncogenes

deactivate Tumor Suppressor genes

Expression of altered cells (Mutation)

Malignant cells