PBL-3: CONSEQUENCES OF SMOKING AND GUTKA

VITALS:

B.P: 110/70 ( Normal range: 120/80 – 140/90)

PULSE: 90/min. ( Normal range: 60 – 100/min)
BMI: 19.5 ( Normal weight: 18.5 – 24.9 )
TEMP: 98 F ( Normal: 98.6 F)
R/R: 20/min ( Normal: 12-20/min)
ANEMIA: Present
CLUBBING: Present
LYMPH NODES: Submandibular lymph nodes palpable on left side.

LEARNING GOALS:

1-BETEL NUT: It is a seed of fruit of areca palm and contains tobacco.

It’s long term effects are discolouration of teeth and ghums, mouth and
stomach ulcer and oral cancers.

2-EXOPHYTIC: It shows something proliferating externally or on the surface

epithelium of an organ or other structure in which the growth originates, Like
tumor that grows into the lumen of a hollow organ rather than into the wall.

3-BUCAL MUCOSA: It refers to the inside lining of the cheeks and floor of the
mouth and is part of the lining mucosa.

4-CLUBBING: It is an abnormality where the ends of the fingers and toes

enlarge and the nails curve, often it is related to an inadequate oxygen rich
blood supply however it can be hereditary. Lung cancer is the most common
cause of clubbing.

5-WHEEZE: It is high pitched whistling sound made while we breathe. It’s

heard most clearly when we exhale but in severe cases it can be heard when
we inhale, It is caused by narrowed airways and inflammation.

6-CARCINOGENESIS: It means initiation of cancer due to some errors in DNA

sequences. It involves three phases Initiation, promotion and progression.
There are some carcinogens for mutations and some physical, chemical and
microbial agents.
PHYSICAL AGENTS: UV radiations, X-rays.
CHEMICAL AGENTS: Tobacco, plastic
MICROBIAL AGENTS: Viral,fungal,bacterial
GENETIC FACTORS: breast cancer, retinal
DIET AND HABBITS: High protein diets.

CELL CYCLE
INTERPHASE.  MITOSIS.  CYTOKINESIS
Actively dividing eukaryote cells pass through a series of stages known collectively as
the cycle cell: two gap phases (G1 and G2); an S (for synthesis) phase, in which the genetic
material is duplicated; and an M phase, in which mitosis partitions the genetic material and
the cell divides.

G1 phase. Metabolic changes prepare the cell for division. At a certain point the restriction
point the cell is committed to division and moves into the S phase.
CHECKPOINT 1: It is after G1 phase to check the correct growth of the cell.
S phase. DNA synthesis replicates the genetic material. Each chromosome now consists of
two sister chromatids.
CHECKPOINT 2: It is after S phase to check that cell has replicated normally.
G2 phase. Metabolic changes assemble the cytoplasmic materials necessary for mitosis and
cytokinesis.

Mitosis:
Mitosis is a form of eukaryotic cell division that produces two daughter cells with the same
genetic component as the parent cell. Chromosomes replicated during the S phase are
divided in such a way as to ensure that each daughter cell receives a copy of every
chromosome. In actively dividing animal cells, the whole process takes about one hour.
Prophase:
Prophase occupies over half of mitosis. The nuclear membrane breaks down to form a
number of small vesicles and the nucleolus disintegrates. A structure known as
the centrosome duplicates itself to form two daughter centrosomes that migrate to
opposite ends of the cell. Spindle fibres are formed.

Prometaphase:
The chromosomes, led by their centromeres, migrate to the equatorial plane in the mid-line
of the cell - at right-angles to the axis formed by the centrosomes. This region of the mitotic
spindle is known as the metaphase plate

Metaphase:
The chromosomes align themselves along the metaphase plate of the spindle apparatus.

Anaphase
The shortest stage of mitosis. The centromeres divide, and the sister chromatids of each
chromosome are pulled apart and move to the opposite ends of the cell, pulled by spindle
fibres attached to the kinetochore regions.

Telophase:

The final stage of mitosis, and a reversal of many of the processes observed during
prophase. The nuclear membrane reforms around the chromosomes grouped at either pole
of the cell, the chromosomes uncoil and become diffuse, and the spindle fibres disappear.
Cytokinesis

Meiosis:
Meiosis is the form of eukaryotic cell division that produces haploid sex cells or gametes
(which contain a single copy of each chromosome) from diploid cells (which contain two
copies of each chromosome).
Meiosis I:

Meiosis I separates the pairs of homologous chromosomes.

In Meiosis I a special cell division reduces the cell from diploid to haploid.

Prophase I:
The homologous chromosomes pair and exchange DNA to form recombinant chromosomes.
Prophase I is divided into five phases:

Leptotene: chromosomes start to condense.

Zygotene: homologous chromosomes become closely associated to form pairs of
chromosomes consisting of four chromatids (tetrads).
Pachytene: crossing over between pairs of homologous chromosomes to form chiasmata.
Diplotene: homologous chromosomes start to separate but remain attached by chiasmata.
Diakinesis: homologous chromosomes continue to separate, and chiasmata move to the
ends of the chromosomes.
Prometaphase I:
Spindle apparatus formed, and chromosomes attached to spindle fibres by kinetochores.

Metaphase I:
Homologous pairs of chromosomes (bivalents) arranged as a double row along the
metaphase plate. The arrangement of the paired chromosomes with respect to the poles of
the spindle apparatus is random along the metaphase plate.
Anaphase I
The homologous chromosomes in each bivalent are separated and move to the opposite poles of the cell

Telophase I:
The chromosomes become diffuse and the nuclear membrane reforms.
Cytokinesis:
The final cellular division to form two new cells, followed by Meiosis II. Meiosis I is a
reduction division: the original diploid cell had two copies of each chromosome; the newly
formed haploid cells have one copy of each chromosome.

MEIOSIS 2
Prophase 2:

Spindle fibers reform and attach to centromeres in prophase II.

Metaphase 2:

The chromosomes align on the metaphase plate during metaphase II in preparation for
centromeres to divide in the next phase.
Anaphase 2:

In anaphase II, chromosomes divide at the centromeres (like in mitosis) and the resulting
chromosomes, each with one chromatid, move toward opposite poles of the cell.

Telophase 2 and Cytokinesis:

Four haploid nuclei are formed in telophase II. Division of the cytoplasm during cytokinesis
results in four haploid cells. In humans, meiosis produces genetically different haploid
daughter cells, each with 23 chromosomes that consist of one chromatid.

DIFFERENCES BETWEEN BENINGN AND MALIGNANT TUMORS

BENINGN:
1- It is localized and non invasive.
2- It tends to have clear boundaries.
3- It has normal shaped DNA.
4- No bleeding is observed at cut surfaces.

MALIGNANT:
1- It is metastasized and insave.
2-It is nucleus prominent and cell membrane disappears
3- It has abnormal shaped DNA.
4- Bleeding is observed at cut surfaces.

TUMOR GRADING
 It shows how abnormal the tumor cell looks and indicates how quickly it
spreads. It has 5 sub types as follow.

1- GX -> Undetermined tumor

2- G1 -> well differentiated tumor
3- G2 -> moderately differentiated
4- G3 -> poorly differentiated
5- G4 -> Undifferentiated

TNM STAGING
TNM stands for tumor lymph nodes metastasis. It is done to classify the extent
of spread of cancer.
T-> shows size or direct extent of primary tumor
*Tx-> tumor can not be assessed
*Tis-> Carcinoma in situ and not invaded
*T0-> No evidence of tumor
*T1-> tumor less then 2cm
*T2-> tumor in between 2-4cm
*T3-> tumor greater than 4cm
*T4-> it has invaded adjacent structures.
Nx-> Not assessed
*N0-> no positive nodes
*N1-> single clinically positive ipsilateral node less than 3cm
*N2-> single clinically positive ipsilateral node in between 3 to 6cm.
*N3-> nodes greater than 6cm

Mx-> Distant metastasis not assessed

*M0-> no distant metastasis
*M1-> distant metastasis is present.

MECHANISM OF CISPLATIN
 It works by binding to DNA and inhibits its replication. Firstly cisplatin
enters the body through active transport and then this drug goes into
nucleus where it forms the bond with guanisine bases and then HNG
protein present there binds to DNA, this protein causes the modified
DNA to not replicate properly and so cell dies.

 Some side effects of this drug includes hearing problems, severe

vomiting and kidney problems.

MECHANISM OF PACLITAXEL

 It works by interfering with normal function of microtubules during cell

division. Paclitaxel treated cells have defects in mitotic spindle assembly,
chromosome segregation and cell division. Chromosomes are unable to
achieve a metaphase spindle configuration. It blocks mitosis and prolonged
activation of mitotic checkpoint triggers apoptosis or reversion to G0 phase.

CLASSIFICATION OF ANTICANCER DRUGS

 Cell cycle specific drugs kill only dividing cell

 Cell cycle non specific drugs kill resting as well as dividing cells.
ALKYLATING AGENTS:
1-Cisplatin, oxaliplatin
2-Chlorambucil

ANTIBIOTICS:
1-Bleomycin
2-Mitomycin C
3-Doxorubicin

ANTIMETABOLITES:
1-5-Fluorouracil
2-Methotrexate

TAXANES:
1-Paclitaxel
2-Docetaxel

CAMPOTHECIN ANALOGUES:
1-Topotecan
2-Irinotecan

VINCA ALKALOIDS:
1-Vincristine
2-Vinblastine

MISCELLANEOUS:
1- Etoposide
2-Imatininb
 SIX PRINCIPLES OF MEDICAL ETHICS:

1-BENEFICENCE: To act in the best interest of the patient.

2-NON-MALFEASANCE: Do not harm the patient.

3-AUTONOMY: The patient right to refuse or choose the treatment.

4-JUSTICE: Everyone should be provided with equal treatment on the merit of

illness.

5-DIGNITY: Patient and doctor both have a right to dignity.

6-HONESTY: The patient deserves to know the whole truth about the illness
and treatment.