CARE OF CLIENTS WITH PROBLEMS IN

CELLULAR ABERRATION, ACUTE BIOLOGIC

CRISIS, EMERGENCY AND DISASTER NURSING
& INTRAVENOUS THERAPY
Nina Anne Bernadette P. Paracad, MSN
LECTURE 1: CELLULAR ABERRATION
SUB-TOPICS:
• Proliferative Growth Patterns
• Characteristics of Cancer Cells
• Tumor Growth
• Molecular Pathophysiology of Cancer
• Carcinogenesis
• Routes of Tumor Spread
CANCER- NOT A SINGLE DISEASE, BUT A GROUP
OF HETEROGENEOUS DISEASE THAT SHARE
COMMON BIOLOGIC PROPERTY.
• Heterogeneous disease— There are various types of Cancer cells. In fact the
number of possible type of cancer cell is as much as the number of different
types of cell in the body.
• Common biologic property- All cancers are genetic and share common
molecular pathogeneses which result in mutations in oncogenes and tumor
suppressors.
• Cell Proliferation – a process of cell division and reproduction

• Normally: Number of cells actively dividing = number of cells dying or being shed
(Therefore, there is regulated proliferation)

Example:

• There are approximately 2.5 M of RBC being destroyed every second.

Therefore, there should be at least 2.5 M RBC cells being produced every
second.
CELL DIVISION/ CELL CYCLE – COORDINATED SEQUENCE OF EVENTS
RESULTING IN DUPLICATION OF DNA AND DIVISION INTO 2 DAUGHTER
CELLS (MITOSIS)

• Mitosis: Initiated by the presence of certain growth factors or other signals

that indicate the need for production of cells.
Somatic cells: fat cells, skin cells, except sex cells
Product: 2 daughter cells (diploid)

• Meiosis: Process by which gametes (sex cells) are generated in organisms

that produce sexually.
Product: 4 daughter cells (haploid)
PROCESS:
• G1- lasts from hours to days
RNA and protein synthesis
Cellular contents except chromosomes are duplicated
• S- Lasts from 10-20 hours
DNA replication
• G2- lasts from 2 hours to 10 hours DNA synthesis stops
RNA and protein synthesis continue
“Double checking” of duplicated chromosomes
• M- Lasts from 30-60 seconds
Cell division occurs
Go- Resting phase
MITOTIC PROCESS
• Prophase- disintegration of nuclear membrane
Formation of centromere
Formation of asther

• Metaphase- centromeres attach to the spindle fibers

Chromosomes line up in the middle of the cell

• Anaphase- centromere split; half chromosome move to opposite pole

Cell membrane begins to pinch at the center

• Telophase- cell division completes

DURATION OF CELL CYCLE

• Varies depending on the cell type, drequency of cell division, and other
characteristics such as growth factors.

• Variability depends on Go-G1 phase

• Very rapidly dividing cells---- 8 hours; other cells----- 1 year

VIDEO
CELL CYCLE TIME
• Amount of time required for a cell to move from one mitosis to another
mitosis

• Varies depending on type of cell

• Cancer cells proliferate at same rate as the normal cells. The difference is
cancer cells proliferate continuously and does not go through Go phase
CHECKPOINTS
• Cyclins— (D,E,A,B)
Protein which activates CDKs

• CDKs- Cyclin Dependent Kinases

Enzymes which serve as checkpoints. They monitor the cell cycle.
2 checkpoints
• G1-S transition
• Checking of DNA damage and ddecides wether to proceed with the
replication
• If there is damage, repair mechanisms are activated and cell cycle is delayed
• G2- M transition
• Verification of accurate DNA replication
• Determines if Mitosis can occur
NEOPLASM- “NEW GROWTH”
• Abnormal mass of tissue characteristics by autonomous, excessive, and
uncoordinated growth
• Classified into benign and malignant (CA)
• Results from abnormal cell differentiation
 CELL DIFFERENTIATION
Process by which the cell acquire specific
structural and functional characteristics until
they become specialized cells.
 APPEARANCE

• Cancer cells struggle to maintain the morphological and functional traints of

the original tissue
• Pleomorphism is the change in size and shape of cancer cells (large and
irregular shape)
• Multiple nuclei
• Aneuploidy is the abnormal number of chromosomes or abnormal
arrangement of chromosome (translocation, deletion, addition)
• Anaplastic- cells appear cytologically disorganized and have no
resemblance to the tissue of origin
 ALTERED METABOLISM
• Changes in cell membrane due to production of surface enzymes that aid I
metastasis and invasion
• Loss of cell-to-cell adhesion and increase in cell mobility due to loss of glycoproteins
that assist in cellular adhesion
• Cell becomes less dependent to oxygen due to the increase rates of anaerobic
glycolysis
• Production of abnormal growth factor receptors leading to uncontrolled cell growth
• Paraneoplastic syndromes are signs and symptoms not directly related to the local
effects of the tumor
• Cancer cells inappropriately secrete hormone-like substances in an organ or tissue
that does not normally produce or release those hormones

• Example: Cell-carcinoma of the lungs----- ADH-------- hyponatremia

Renal carcinoma-------------Erythropoietin---- polycythemia
 TUMOR SPECIFIC ANTIGENS
• These are antigens produce by the tumor cells. Tumor markers for example
are produced by tumor cells and are often used to screen and diagnosed
individuals with cancer.

A. Hormones
• HCG--- trophoblastic tumor, testicular CA
• Calcitonin--- medullary carcinoma of the thyroid

B. Oncofetal Antigens
• Carcinoembryonic-carcinoma of colon, pancreatic Ca, lung CA, gastric CA

C. Isoenzyme-
• Prostatic acid phosphate—prostate CA

D. Specific proteins
• PSA—prostate CA

E. New Molecular markers

• P53, APC, and RAS (stool and serum)--- colon cancer
 ALTERED CELLULAR FUNCTION

• Uncontrolled cell proliferation

Normally—(+) stimulus---------- Proliferation
(-) Stimulus---------- (-) Proliferation

• Therefore there is balance between cell production and cell loss

• Cancer cells—uncontrolled proliferation------- uncontrolled cell growth

• Loss of contact inhibition
• Normally, cells stop movement when they come in contact with
another cell and symmetrically arrange themselves around each
other. Cancer cells tend to invade other cells that they come in
contact with.
• Normal cells stop to divide when they are surrounded by other
cells. Cancer cells continue to pile on top of each other
• Chromosomal Instability------ Increase in malignant cells---------
malignancy
• Metastasis- Spread of cancer cells from a primary site to distant
secondary site
• Doubling Time
• Length of time it takes for a tumor to double its volume
• Tumor cells undergo series of doublings as the tumor increase in size (Average- 2
mos)
• Rapidly growing tumor-(testicular cancer)---- every month
• Slow growing tumor-(prostate cancer)------ every year
• Factors affecting doubling time
• Cell-cycle time
• Growth fraction
• Cell loss (cell death, differentiation, metastasis)
• It takes 10 years for a tumor to reach 1 cm size which is the size of
tumor to be clinically detectable. Tumors need to undergo doubled
rime 30 times to produce 1 billion cells and gain 1 g weight.
• Growth Fraction
• Ration of the total number of cells to the number of dividing cells
• Increase in growth fraction---increase in tumor volume quickly
• As tumor volume increases---- growth fraction decreases

• Gompertzian growth curve

• When the cell death is equal to the cell birth (plateau) there will still be
continuous but slower growth in tumor.
FACTORS CONTRIBUTING TO CELLULAR
MALIGNANCY

1. Self-sufficiency in growth signal

• Proto-oncogenes—normal genes that regulate
normal cell growth and repair
• Oncogenes--- altered proto-oncogens that
promote autonomous cell growth in cancer
cells
2. Insensivity to growth-inhibitory signals
• Tumor-suppressor genes---- “Brakes of the cell”
Types:
• Gatekeeper genes—directly contros the growth of tumors by
inhibiting cell proliferation and or promoting cell death
(Apoptosis)
• Inactivation of the gatekeeper genes will result into
uncontrolled proliferation
• Caretaker genes—control the rate of mutation
• Mutation of caretaker genes result into genetic instability. This
will further result into increase mutation and malignancy,
hence, the uncontrolled growth of tumor
3. Evasion of Apoptosis
• Mutation in genes that control cell death (programmed cell death)
4. Defects in DNA repair----- malignancy

5. Limitless replication potential

• Telomeres—structure at the end of each chromosome that shorten
in every cell division. Once they shorten beyond a certain point,
proliferation ceases or apoptosis occurs.

• Telomerase--- enzyme in cancer that prevents shortening of the

telomere thus enabling cells to self-replicate
7. Sustained Angiogenesis
• Angiogenesis- Formation of vascular supply to sustain blood vessel growth.
• Vascular Endothelial Growth Factor (VEGF) --Angiogenic factors produced
by the tumor cells to stimulate angiogenesis.

8. Ability to invade and metastasize

• Invasion—growth of primary tumor into the surrounding host tissue
• Metastasis- spread of cancer cells from a primary tumor to distant sites of the
body
• Carcinogenesis
• The process of malignant transformation
• 1941- Rous and Kidd--- 2 stage theory
• 1947—Berenblum and Shubik—3 stage theory
(initiation, promotion, progression)

• Carcinogens
• Agents that initiate or promote cellular transformation
 CLASSIFICATION OF CARCINOGEN
• Initiating Agent
• Chemical, biologic or physical agent capable of producing
irreversible changes in the DNA and cell
• Promoting Agents
• Hormones, plant products, chemicals and drugs
• Complete carcinogen (Co-carcinogen)
• Chemical carcinogens that can both initiate and promote
malignancy
• Cigarette smoking
• Cancer suppressing/ cancer-reversing agents
• Vitamins, minerals, carotenoids, flavonoids
 SOURCES OF CARCINOGENS

1. Heredity/ Genetic and Familial factors

• Hallmarks of family predisposition to cancer
• Cancer in 2 or more first degree and 2nd degree
• Early onset of CA in family members (<50 years)
• Same type of Cancer in one or more family
members
2. Hormonal Factors
• Disturbance in hormonal balance
• Diethylstilbestrol (DES)—causes vaginal carcinoma
• Contraceptives
• Early menarche (<12 y.o)
• Delayed menopause (>55 y.o)
• Delayed childbirth (>30 y.o)
• Nulliparity
3. Environmental Agents
A. chemical agents
• Tobacco smoke is the most lethal chemical carcinogen
• Effect of second hand smoker
B. Physical agents (Radiation)
• Exposure to UV rays
• Exposure to ionizing radiation
• Radiation therapy
• Cells in G2 phase are more sensitive to radiation
than cells in S or G1 phase
C. Viruses
• Human Papilloma Virus
• (Cervical carcinoma, anal carcinoma)
• Epstein- Barr virus (EBV)
• (Burkitt’s lymphoma, B-cell lymphoma, nasopharyngeal carcinoma)
• Hepatitis B Virus (HBV)—Hepatocellular carcinoma
• HT LV-1- Human T-cell leukemia Virus 1 (T-cell leukemia)

D. Bacteria and Parasites

• Helicobacter Pylori- first bacteria that was found to cause CA
(Gastric lymphoma, gastric carcinoma)
• Scistosoma hematobium- parasites linked to bladder and liver
CA
• Human Papilloma Virus (HPV)- cervical/anal carcinoma
• Epstein-Barr Virus (EBV)- Burkitt’s lymphoma, B-cell lymphoma,
nasopharyngeal carcinoma
4. Immune System Deficiency/ies
• Normally when a developing tumor expresses a
tumor-associated antigen, the immune system
recognizes these antigen as foreign and destroys
the cancer cells.
• Cytotoxic T-cells—Works for immunologic
surveillance. With receptors of specific tumor
antigens, and natural killer lymphocytes,
macrophages and B-lymphocyte.
 WAYS IN WHICH CA CELLS BYPASS
SURVEILLANCE

1. Tumor-cell camouflage
• In the early phase of growth, the tumor antigen
may be weak and thus, do not promote an
immune response until the CA is too large for the
immune system to destroy
2. Antigenic Modulation
• Cancer cells may change or lose antigens in
response to recognition by the immune system
3. Overwhelming antigen exposure
• CA cells may express an excess of Tumor-Associated
Antigen. The antige bind to specific antibodies or to
lymphocyte receptors
4. Blocking agents
• Blocking antibodies may bind with TAA/TSA antigen to
prevent recognition by T-cells or free antigen produced by
the Cancer cells binds with T-cells to prevent recognition of
the CA cells
 METASTASIS

Spread of cancer cells from a primary tumor to organs and distant sites in the
body
 STEPS:

1. Growth and progression of the primary tumor (1st requirement of

metastasis)
• TUMORS MUST REACH 1 BILLION CELLS or 1 CM IN SIZE BEFORE METASTASES CAN
TAKE PLACE
2. Angiogenesis at the primary site
• Tumor releases angiogenic factors to stimulate new caoillary formation
• Tumor vascularity allows growth of tumor and spread
3. Local invasion
4. Detachment and embolization
• Tumor cells aggregate with blood cells, primarily platelets, and form fibrin in
platelet emboli to protect themselves and to promote metastases by adhering
to capillary walls of target organs
5. Arrest in distant organ capillary beds
• Cancer cell attachment
6. Extravasation
• Penetration to vessel wall
7. Proliferaion
 ROUTES OF TUMOR SPREAD

• Direct extension / local invasion of adjacent

organs
• Metastases by implantation of serosal seeding
• Metastases to distant organ by lymph/
circulatory system
 DIRECT EXTENSION / LOCAL INVASION OF
ADJACENT ORGANS

• First step in metastatic process

• Mechanism:
• Tumor Growth ----- Increase mechanical pressure
• Tumor secreted enzymes---- decrease cellular
adhesion---increase motility-----escape and
invade
 SEROSAL SEEDING

• Tumors have invaded a body cavity from surrounding tissue and attach to
the surface of an organ within the cavity
LYMPHATIC SYSTEM
 CIRCULATORY SYSTEM

• Tumor cells follow the flow of venous that drain the site of the neoplasm