Professional Documents
Culture Documents
L11, Pathophysiology Manual
L11, Pathophysiology Manual
L11, Pathophysiology Manual
College of Pharmacy
Aim: To learn the concepts of cancer, its origin and its harmful effects on the body and life.
Key concepts:
Cancer means, an altered cell growth and differentiation. The cancerous tissue also called Neoplasm
(Greek: means new formation). The term Tumor means swelling caused by many factors (trauma or
inflammation). Tumor and neoplasm are often interchangeable. In cancers, cell growth is
uncoordinated and autonomous (self-directed). The cells lack normal regulatory control over growth
and differentiation; hence they continue to grow and to increase in size after removal of the stimulus.
Cancers are divided into Benign and Malignant. Malignant cancers are toxic cells that can metastasize
from primary to secondary origins due to lacking normal adhesiveness to tissue cells producing
harmful effects there. Too undifferentiated cancers are the most malignant one. They cannot be
detected early unless they are in late stages. Cancer cells have mutant genes arising from many causes
including heredity, radiation, some viruses and immunologic defects. When their toxic effect appears
they can be diagnosed, graded and treated. The main goal of treatment is to prevent their further
metastasis and increase life expectancy.
Outcomes: at the end of this lab., the students should be able to describe the concept, types,
metastasis, causes, diagnosis, prognosis and treatment strategies of cancers.
Demonstration tools: Data show and posters
Evaluation: Case study exam
M.S., a 45-year-old woman, presents to her primary care physician with a palpable lump in her
left breast. She reports noticing the lump about a month ago and mentions occasional breast
pain. Mrs. Smith has no significant family history of breast cancer, but she does have a history of
hormonal replacement therapy for menopausal symptoms. The physician orders a mammogram,
which reveals a suspicious mass. A biopsy confirms the presence of invasive ductal carcinoma.
T.J., a 50-year-old woman, presents to her oncologist with complaints of persistent fatigue,
unexplained weight loss, and swollen lymph nodes. She reports experiencing night sweats and
intermittent fever over the past few months. Physical examination reveals enlarged cervical and
axillary lymph nodes. A biopsy of the lymph node confirms the diagnosis of diffuse large B-cell
lymphoma (DLBCL), a common type of non-Hodgkin lymphoma.
R.M., a 55-year-old man, presents to his hematologist with complaints of persistent fatigue,
unintentional weight loss, and abdominal discomfort. Routine blood tests reveal an elevated
white blood cell count and the presence of the Philadelphia chromosome. Further diagnostic
tests confirm the diagnosis of Chronic Myeloid Leukemia (CML).
Uruk University 3rd stage, Pathophysiology Lab
College of Pharmacy
Cancer
Proliferation Means the cell division. It is normal highly regulated process for replacing
old and damaged cells with new ones. It is highly regulated (no. of actively
dividing cells = no. of died cells)
Differentiation Means the specialization. It is normal process for getting similar
structural, functional features and life expectancy of replaced cells (e.g.;
RBC: Concave, hold O2, live for 120days) . Anaplasia = lack of differentiation
The size of cell population is determined by: proliferation rate, differentiation rate and apoptosis
Cell cycle
Stable cell (like hepatocytes) enter quiescent period (G0) and can re-enter S phase in response to
nutrients, growth factors, hormones, tissue injury, ischemia and signals for re-newel.
Uruk University 3rd stage, Pathophysiology Lab
College of Pharmacy
Differentiation: Involves several steps. With each progressive step specialization increase
and ability to develop different characteristics is lost.
Types of neoplasm
Benign or Malignant and are recognized according to: (1) Differentiation (2) Rate of growth
(3) Metastasis (4) General effect (5) Tissue destruction (6) Ability to cause death.
Uruk University 3rd stage, Pathophysiology Lab
College of Pharmacy
Naming of tumor
By adding suffix – oma, carcinoma or sarcoma to the parenchymal tissue type from which the
tumor is originated
For Benign – oma
- Glandular epithelium – adenoma
- Bone - ostoma
For Malignant epithelial origin – carcinoma
Glandular epithelial tissue – adenocarcinoma
For Malignant mesenchymal origin – sarcoma
Bone – osteosarcoma
Benign microscopic or macroscopic fingerlike projections from mucosal surface – papilloma
Growth of projections from mucosal surface as in the intestine - polyp
Malignant neoplasms
Growth and spread: Rapidly growing and spread widely (metastasize)
Fatality: Fatal regardless of their location; compress blood vessels producing ischemia and
necrosis
Toxicity: Liberate enzymes, toxins and hormones that destroy tumor and normal supporting
tissue
Proliferation and differentiation: are fail
Malignancy: if occur in the early steps of the process – highly malignant. if occur in the late
steps of the process – less malignant
Types: (1) Solid, (2) hematologic
Uruk University 3rd stage, Pathophysiology Lab
College of Pharmacy
Differences from normal: anaplastic cells differ from original tissue cells in that they have:
1) Altered nucleus size
2) Altered shape
3) No function (lack of metabolic pathways)
4) Non-endocrine cancer may produce ectopic hormones
5) Do not die in normal time schedule
6) Resemble each other (e.g.; leukemic cells)
7) Loss contact inhibition (loss growth stop after cell come in contact with another cell)
8) Loss cohesiveness (cell shedding)
9) Loss cell-to-cell communication (no response to external stimuli)
10)Express altered tissue antigens (help recognized as foreign by immune system)
11)Release destructive enzymes (fibrinolysin, proteases and glycosidase destruct matrix
proteins)
Metastasis
Means: development of secondary tumor in location distant from the primary tumor
Characters: retains many characteristics of primary tumor making the detection of the
primary site possible.
Onset: may be in the early or in the late stage of the tumor development
- Malignant tumor of kidney metastasize into lung even that the kidney tumor is
asymptomatic and undetected.
Seeding: spread of the tumor into the body cavities (peritoneal, plural, synovial cavities)
- seeding in the peritoneal cavity is common in ovarian cancer
Tissue reaction: Lack of demarcation line, fibrous capsule and low inflammatory reaction
making the tumor spread undetectable and cannot be removed by surgery
Ways of spread: either lymphatic spread or hematogenic spread
- Cancer is first disseminated into and lodges in the lymph node drain the area of neoplasm.
Tumor cell may die in these lymph nodes (lack of proper environment, killing by
lymphocytes) or may survive and enter venous circulation
- Blood-born tumor cells follow the venous flow that drains the area of neoplasm.
Neoplasms in stomach, intestine, spleen and pancreas commonly metastasize to liver. But
some uncommonly metastasize to far distances.
Distant metastasis is favored by availability of growth factors or hormones for survival.
- Even 1/10,000 shed primary tumor cell can induce the growth of secondary tumor
- Once in the secondary site, tumor cells induce angiogenesis by releasing angiogenic
factors
- In tissues lack the stimulatory factor or have inhibitory factors, tumor cells do not survive
Uruk University 3rd stage, Pathophysiology Lab
College of Pharmacy
Carcinogenic agents produce damage in these genes and causing activation of many
independently mutated genes Cancer
Mutated P53 gene is linked to lung, breast and colon cancer
Cells retain P53 genes respond to chemotherapy than those with mutated one.
Heredity
50 types of cancer are related to heredity
Breast cancer in grandmother, mother, aunt, sister linked to 1st degree family member
breast cancer
- 10% in female have 1 affected family member
- 15% in female have 2 affected family members
- 30% in female have 3 affected family members
- The risk increase to 50% in >65Y woman having multiple members with breast cancers
- Two variant oncogenic genes were detected to be hereditary affected
Breast carcinoma 1 (BRAC1) gene
Breast carcinoma 2 (BRAC2) gene
These are DNA repairing genes
Carcinogenic agents
Carcinogens
Both form highly are reactive electrophiles or free radicals attack DNA, RNA and proteins
Thus induce gene mutation, alter synthesis of enzyme and regulatory molecules
Carcinogenicity of promotor agents increased by lifestyle risk factors (smoking, dietary
factors, alcohol consumption)
- Cigarette smoking promotes lung, laryngeal, esophageal, pancreatic, renal, uterine cervix,
and bladder cancers.
- Bezo[a]pyrine is a polycyclic hydrocarbon converted to carcinogen when fat reused many
times
- Nitrosamines used in vegetable and food preservatives are converted to carcinogens
when meat and fish are boiled or smoked.
- High fat, protein and beef with low dietary fibers associated with colon cancer
Uruk University 3rd stage, Pathophysiology Lab
College of Pharmacy
Radiation Oncogenesis
A. High energy ionizing radiation can be encountered in radiological warfare; medicine and
industry. It commonly induces skin cancer and leukemia. The effect depends on the dose;
the gender and the age at which the individual exposed.
Ex: 25-30 years of whole body exposure or trunk exposure to radiation increased
incidence of leukemia and breast, lung, stomach, thyroid, salivary gland, GIT and lymphoid
tissue cancers.
- If the child exposed to radiation in utero leukemia after 2-3 years after birth
- If the child exposed to radiation in childhood leukemia after 5-10 years and certain
tumors after 20 years after birth
- Irradiation of head and neck to decrease size of thymus or tonsils thyroid cancer after 35
years of exposure
B. Low energy radiation such as ultraviolet light does not deeply penetrate the skin. It
causes skin cancers and there is a long delay between exposure and appearance of skin
cancer
Oncogenic Viruses
Immunologic Defects
Immune surveillance hypothesis by Paul Ehrlich in 1909 say that our immune system
participates in the resistance against the progression and spread of cancer
Immunological mechanisms provide a mean for cancer (1) Detection (2) Classification (3)
Prognosis and (4) Therapy
Immune system is compromised in AIDS, autoimmune diseases, chemotherapy, organ
transplant and advanced age (e.g.; Kaposi sarcoma in AIDS patients)
Most tumor cells have surfaces tumor antigens that can be detected and attacked by T-
lymphocytes (CD8+ T-cell).
The antibodies of B-cell link tumor cell to natural killer (NK) cells and also activate the
complement system. IL-2, lymphokines and interferons augments the killing effect of NK
Macrophages are antigen presenting cells (APC) that participate in tumor cell lysis.
Uruk University 3rd stage, Pathophysiology Lab
College of Pharmacy
Diagnosis
1. DAP smear
2. Biopsy
3. Tumor markers
4. Blood samples
5. Imaging (X-ray, computerized tomography “CT scan”, Magnetic resonance imaging “MRI”, A
positron emission tomography “PET scan”)
CT scan looks at the structure of organs
Prostate cancer, uterine cancer, and certain liver cancers, are much invisible or very hard
to detect on a CT scan; in addition, metastases to the bone and brain also show up better on
an MRI.
PET scan: can find abnormal activity and it can be more sensitive than other imaging tests
in detecting cancer by looking at their function and shows unusual cellular activity.
DAP smear # exfoliative cytology: Looking for exfoliated tumor cells in the secretion
surrounding the tumor growth
In cervical cancer, DAP smear done annually between 18-45 years
Example of fluids examined:
- Nipple drainage
- Pleural fluid
- Peritoneal fluid
- Gastric washings
Staging
Treatment
1. Surgery
2. Radiotherapy
3. Chemotherapy
4. Hormone and anti-hormone therapy
5. Biotherapy (Active and passive immunity)
6. Organ transplant