ALTERATIONS IN CELLULAR REGULATION AND GENETICS
CELLULAR REGULATION
What is Cellular Regulation?
Cellular regulation refers to the processes that control cell growth, replication, and function. It ensures that cells work correctly, repair damage, and replace old or dying cells. Disruption in cellular regulation can lead to serious health problems like cancer, anemia, or autoimmune diseases.
Types of Cellular Changes
Normal: Standard cell function and maintenance.
Hyperplasia: Increased cell number.
Atrophy: Decreased cell size.
Metaplasia: Conversion of one cell type to another.
Hypertrophy: Increased cell size.
Dysplasia: Disorderly growth.
Cancer
Cancer is a destructive (malignant) growth of cells, characterized by rapid division, invasive behavior, and the potential to metastasize, which refers to the spread of cancer cells beyond the original site. Cancer cells are typically more aggressive than normal cells.
Mechanisms of Metastasis
Direct Invasion: Cancer cells invade nearby tissues and organs.
Circulation: Travel through the blood or lymphatic system.
Direct Transportation: Cells may be moved unintentionally during medical procedures.
Carcinogenesis (Oncogenesis)
All cancers result from gene malfunctions that regulate cell growth and division. The transformation from a normal cell to a cancerous cell is referred to as carcinogenesis, influenced by various factors, including viruses, carcinogens (physical/chemical), genetics, diet, immune function, metabolism, and hormones.
Malignant Tumors
Malignant tumors are cancerous growths with the ability to invade surrounding tissues and metastasize. They are characterized by:
Key charatersistics
Rapid, uncontrolled growth: Cells divide excessively and do not respond to normal growth control signals.
Invasion of nearby tissues: Malignant cells destroy normal structures by invading surrounding tissues.
Metastasis: Proliferation through the bloodstream or lymphatic system to distant organs (e.g., lung cancer spreading to the brain).
Abnormal cell structure: Features irregular shapes, large nuclei, often disorganized appearance under a microscope.
Genetic mutations: DNA changes lead to unregulated growth and evasion of apoptosis (normal cell death).
Angiogenesis: Formation of new blood vessels to supply tumors with oxygen and nutrients for continued growth.
Resistance to treatment: Ability to develop resistance to chemotherapy, radiation, and immune responses.
Tumor Nomenclature
Malignant tumors are classified based on their origin:
Carcinomas: Arising from epithelial tissues.
Adenocarcinomas: Glandular tissues.
Sarcomas: Connective, muscle, and bone tissues.
Gliomas: Brain and spinal cord tissues.
Melanomas: Pigment skin cells.
Myelomas: Plasma cells.
Lymphomas: Lymphatic tissue.
Leukemias: Blood cells. (the only one thats a little bit different)
Tumor Staging and Grading
The later the stage it is metasised.
T Classification: Defines the primary tumor size and extent:
TX: Primary tumor cannot be measured.
T0: Primary tumor cannot be found.
T1-4: Measured tumor; higher numbers indicate larger size or more extensive spread into nearby tissue.
N Classification: Evaluates lymph node involvement:
NX: No information on lymph nodes.
N0: No cancer in nearby lymph nodes.
N1-3: Presence of cancer in lymph nodes; higher numbers indicate more nodes involved.
M Classification: Assesses metastasis:
MX: Metastasis cannot be measured.
M0: No spread to distant parts of the body.
M1: Spread present to distant body parts.
Stage 0: cancer cells found in their earliest form
Stage 1: A small tumor that hasnt spread
Benign Tumors
Benign tumors are non-cancerous growths that do not invade nearby tissues or metastasize.
Key Characteristics of Benign Tumors
Slow growth and LOCALIZED: Gradual increase in size over time.
Encapsulation: Often enclosed in a fibrous capsule, preventing tissue invasion.
Non-invasive: Do not spread to other body parts.
Well-differentiated cells: Cells resemble normal tissue and function similarly.
Minimal health risks: Many benign tumors are asymptomatic and often require treatment only if symptomatic.
Rare recurrence: Less likely to return after surgical removal compared to malignant tumors.
Examples of Benign Tumors
Adenomas: Glandular tissue tumors.
Lipomas: Fat tissue tumors, typically found under the skin.
Fibromas: Tumors of fibrous tissue, commonly found in the uterus.
Hemangiomas: Abnormal blood vessel growths, often appearing as birthmarks.
Meningiomas: Tumors in the membranes covering the brain and spinal cord.
Cancer Statistics
Cancer is a leading cause of death in the United States, causing 1 in 4 deaths.
Most Common Forms of Cancer:
Prostate cancer
Lung cancer
Skin cancer
Early Detection
Early detection of cancer or cardiovascular diseases often leads to more effective treatment and better prognoses. A critical aspect is thorough assessment, including inquiries about risk factors:
Cigarette smoking history.
Family history of cancer.
Exercise patterns and diet.
Exposure to potential hazards (e.g., asbestos).
CAUTION Mnemonic for Assessment
C: Change in bowel or bladder habits.
A: A sore that doesn’t heal.
U: Unusual bleeding or discharge.
T: Thickening or lump.
I: Indigestion or difficulty swallowing.
O: Obvious changes in a wart or mole.
N: Nagging cough or hoarseness.
Risks and Cancer Factors
Viruses and Cancer
Some viruses can alter cell genetics, increasing cancer risk:
Epstein-Barr Virus (EBV): Linked to Burkitt lymphoma, Hodgkin disease, nasopharyngeal cancer.
Human Papillomavirus (HPV): Related to cervical, vulvar, anal, oropharyngeal, and penile cancers.
Hepatitis B and C Viruses: Associated with hepatocellular (liver) carcinoma.
Human T-Cell Lymphotropic Virus: Linked to adult T-cell leukemia.
HIV: Connected to Kaposi sarcoma.
Radiation and UV Exposure
UV radiation (from sun exposure, tanning beds) linked to skin cancers:
Squamous Cell Carcinoma
Basal Cell Carcinoma
Melanoma
Radiation exposure can cause tumors, with risk factors including tissue type, age, exposure duration, and hormone levels.
Environmental Carcinogens
Certain substances have the potential to damage DNA, increasing cancer risk:
Tobacco: Associated with lung, pancreatic, kidney, bladder, mouth, and esophageal cancers.
Asbestos & Airborne Hydrocarbons: Linked to lung cancer.
Alkylating Agents: Connected to leukemia. (Medications→ chemo)
Immune System and Cancer
Weakened immunity can heighten cancer risk, particularly in:
AIDS patients
Transplant recipients on immunosuppressants: Increased risk of Kaposi sarcoma, non-Hodgkin lymphoma, and skin cancer.
Diet and Cancer Risks
Colorectal cancer risk factors include:
Low-fiber, high-fat diets.
High consumption of red/process meats.
Heavy alcohol use and long-term smoking.
Ingestion of nitrates and charbroiled foods. (carcinogen)
Hormones and Cancer
Hormones can INCREASE or DECREASE cancer risk
Hormonal changes can influence cancer risk, with excess estrogen linked to certain cancers while reducing the risk of others.
Hereditary Cancers
Approximately 5% of all cancers are strongly linked to inherited genetic mutations, which may be:
Autosomal Dominant
Autosomal Recessive
X-Linked Disorders
Common Characteristics of Hereditary Cancers
Early onset of cancer.
Higher risk of bilateral cancer in paired organs (e.g., breasts, adrenal glands, kidneys).
Increased incidence of multiple primary cancers across different organs.
Presence of abnormal chromosomes in tumor cells.
Unique combinations of tumor sites.
Multiple family members diagnosed with the same cancer.
Cancer Treatments
3 Main Goals
Elimination
Managing
Control the spread
Types of Cancer Treatments
Palliative care (confort care)
Chemo and radiation
Immunotherapy
Surgery
Stem cell therapy + bMT
Hormonal tx
Supporive care
Pain management
hospice
Pleur x catheter (permanent chest tube)
Nurtritional needs
DANA-FARBER CANCER INSTITUTE
Cancer Prevention Tips
Stop or Never Start Smoking: Leading cause of lung cancer and related to other cancers.
Exercise: Regular physical activity lowers cancer risk and recurrence.
Moderate Alcohol Consumption: Linked to various cancers.
Know Your Family History: Consult about genetic counseling if there’s a strong history.
Wear Sunscreen: Protects against skin cancer.
Get Immunized: Vaccines for HPV and hepatitis B can prevent respective cancers.
Practice Safe Sex: Reduces risk of sex-related cancers.
Get Regular Check-Ups: Essential for monitoring health.
Limit Consumption of Red Meats: Linked to various cancers.
Maintain a Healthy Weight: Obesity is a known risk factor for cancers.
Sources: World Cancer Research Fund International
GENETICS
What is Genetics?
Genetics is the study of heredity, which is the passing of traits from biological parents to their children. This includes physical traits like hair and eye color, as well as biochemical and physiological traits, such as a predisposition to certain diseases or syndromes.
Transmitting an Inheritance
Inherited traits are passed down from biological parents through genes in germ cells or gametes (eggs and sperm). A person's genetic makeup is established at fertilization when the egg and sperm combine. Within germ cells are chromosomes made of DNA, consisting of thousands of genes. These genes carry information for inherited traits, such as blood type, color, and physical features.
Chromosomes and Zygote Formation
A human egg cell (ovum) and a sperm cell each contain 23 chromosomes. Their pairs form when fertilization occurs, creating a fertilized cell called a zygote, which has 46 chromosomes (23 pairs).
Cell Division and Chromosomes in Development
The zygote undergoes mitosis, enabling each 46 chromosome to replicate. This process continues, resulting in cells forming a fully developed human body, where every cell (except for egg and sperm cells) contains 46 identical chromosomes. Ova and sperm are produced through meiosis, a division process that results in gametes each containing one set of 23 chromosomes.
Gene Location and Pairing
The specific location of a gene on a chromosome is referred to as its locus. Thousands of genes exist, each having unique characteristics that remain constant across individuals. The Human Genome Project has mapped all gene loci. During fertilization, gene pairs form—one from the mother and the other from the father.
Alleles and Expression
An allele represents a variation of a gene controlling a trait (e.g., eye color). Inheritance may involve different combinations of alleles:
Homozygous: Identical alleles.
Heterozygous: Different alleles.
Dominant alleles require just one copy for trait expression, whereas recessive alleles require both copies.
Chromosomes and Sex Determination
Humans have 23 pairs of chromosomes; 22 pairs are autosomes, while the 23rd pair are sex chromosomes. Males produce sperm that carry either an X or a Y chromosome—fertilization with an X results in a female offspring, and a Y results in a male offspring.
Female: XX
Male: XY
What is a Mutation?
A mutation is a permanent alteration in genetic material, potentially producing a new trait. Mutations in gametes can be passed to offspring and can cause serious disorders in three forms:
Single-Gene Disorders
Chromosomal Disorders
Multifactorial Disorders
Single Gene Disorders
Single-gene disorders have identifiable inheritance patterns:
Autosomal Dominant: Affected males and females are equally impacted. An affected parent contributes a 50% chance of an affected child.
Example: Marfan syndrome.
Autosomal Recessive: Offspring of unaffected parents can be carriers, presenting a 25% chance of being affected.
Sex-Linked Inheritance: Disorders are passed through sex chromosomes, most commonly the X chromosome.
Single-gene disorders are inherited in clearly identifiable patterns. Two important inheritance patterns are called autosomal dominant and autosomal recessive
Autosomal Dominant Inheritance
Affected males and females have equal chances of transmission.
One of the biological parents is also usually affected
An affected parent usually has a 50% chance of affecting their offspring.
If both parents are affected, all their children will likely be affected.
Autosomal Dominant Inheritance on Punnett Square
The affected parent
passes the altered gene
to half the children.
Affected Parent
A
a
a
Aa
a
Aa (affected), aa (unaffected)
Affected Unaffected
### Autosomal Recessive Inheritance
- Affected males and females are equally impacted.
- If both parents are carriers (unaffected), children have a 25% chance of being affected.
#### Autosomal Recessive Inheritance on Punnett Square
Heterozygous Parent Heterozygous Parent
A a A a
/ A A A
AA (unaffected) Aa (carrier) Aa (carrier) aa (affected)
Only a child
who receives
two altered genes
develops the disorder.
Autosomal recessive inheritance
Male and female are affected equally
If both biological parents are unaffects but heterozygous for the trait (carriers), each of their biological offspring has a one in four chance of being affected
If both biological parent are affected, all of their biological offspring will be affects
BEING AFFECTED is NOT the same as BEING A CARRIER
Sex-Linked Disorders
Genetic disorders from genes located on sex chromosomes are termed sex-linked, predominantly concerning the X chromosome. Males, having only one X chromosome, are more frequently affected by X-linked disorders.
Because males have only one x chromosome a single x linked recessive gene can cause disease in a male. In comparrison a female need TWO copies of the diseased gene.
Therefore, males are more commonly affected by x-linked recessive diseases than females
X-Linked Dominant Inheritance
An affected individual usually has one affected parent.
If the father is impacted, all daughters are affected; sons aren’t.
If the mother has the disorder, there’s a 50% chance that a child of either sex will be affected.
X-Linked Recessive Inheritance
Most affected individuals are males with unaffected parents. Female offspring of affected fathers are carriers.
Hemophilia serves as an example of an X-linked recessive disorder.
All of the female offspring of an affected biological father will be carriers
Male offspring of an affected biological father are unaffected. Unaffected male offspring cant transmit the disorder
Chromosomal Disorders
Chromosomal aberrations involve changes in chromosome structure or number leading to genetic issues caused by nondisjunction, where chromosomes fail to separate adequately during cell division.
Nondisjuction occurs when chromosomes fail to seperate correctly during cell division, leading to an unequal distribution of chromosomes.
Monosomy: Missing chromosome; associated with Turner syndrome.
Trisomy: Extra chromosome; often results in Down syndrome. Nondisjunction risk rises with maternal age.
The likelihood of nondisjunction increases with material, age, and it can lead to miscarriages
Multifactorial Disorders
These disorders arise from genetic and environmental factors, with contributing factors including maternal age, chemical exposures, infections during pregnancy, and nutritional statuses.
Examples are:
Cleft lip
Cleft palate
myelomeninggocle (spina bifida with a portion of the spinal cord and membranes protruding
Sickle Cell Anemia
What is Sickle Cell Anemia?
An inherited autosomal recessive disorder characterized by abnormal hemoglobin and irregularly-shaped erythrocytes, diagnosed through newborn blood screening like hemoglobin electrophoresis. Symptoms arise during hypoxia or stress (infection, trauma, increased altitude, dehydration) , leading to tissue ischemia and potential organ damage over time.
Sickled RBCS or stiff, mishapen (sickle shaped), and clog small capillaries, Clinical Manifestations causing tissue ischemia
Over time, all body systems may become affected, causing end organ damage and death
Common Symptoms:
Jaundice (eyes-sclera)
Pallor (conjunctiva, muscous membrane)
Pain (joints, chest,back, long bones)
Fatigue
Concerning Symptoms:
Fever (infection)
Dyspnea (acute chest syndrome)
Chest pain (acute chest syndrome)
Headaches, dizziness, vision issues. (stroke)
Spelnic sequestration
Genetic Transmission
If both parents carry the sickle cell trait, the probabilities are:
25% chance of sickle cell disease
25% chance of a normal child
50% chance of having a child with sickle cell trait.
Treatment Approach
Aim to prevent organ damage and alleviate symptoms. Hospital treatment during crises may include:
Oxygen therapy
Fluid and electrolyte support
Anticoagulation therapy
Pain management
Hydroxyurea to increase hemoglobin
Folic acid to prevent meggloblastic anemia complications
Blood transfusions, stem cell transplants, gene therapy.
Conclusion
This comprehensive overview details mutations, genetic disorders, cellular regulation, cancer growths, and treatment options, emphasizing the significance of early detection and understanding genetic predispositions in managing health conditions effectively.
That's all Folks!