Apprenticeship Learning Log

 

Date of Learning: 29/10/25

Time: 9:30 – 16:30

Title of learning activity: Complex Genomics: Cancer, Sickle Cell.

End of Life.

 

Diary of Learning activity

(itemise learning activity and reflect on the main points of learning from each. You should identify for each entry the relevant KSB)

Reflection on Learning Activity (include model of reflection e.g. Driscoll or Gibbs):

 

 

Cancer is a group of diseases in which cells acquire changes (mutations and epigenetic alterations) that let them grow, survive, and spread uncontrolled. Those altered cells form a mass (tumor) for solid cancers or expand in blood/bone marrow for blood cancers (leukemias, lymphomas). Cancers are heterogeneous — even cells within one tumor differ from each other.

 

Pathophysiology — what goes wrong

Cancer develops through stepwise genetic and cellular changes that let cells escape normal control:

• Driver mutations: Changes in oncogenes (e.g., RAS, EGFR) and tumor suppressor genes (e.g., TP53, RB1) disrupt growth, death, and DNA repair. (PMC)
• Hallmarks of cancer: Cells gain abilities to proliferate, resist death, induce angiogenesis, and invade/metastasize — plus newer traits like immune evasion and altered metabolism.
• Genomic instability: Defective DNA repair (e.g., BRCA1/2, mismatch repair) causes mutation accumulation, fueling cancer and guiding targeted therapies. (NCBI)
• Tumor microenvironment: Cancer cells co-opt stromal, vascular, and immune cells to promote angiogenesis, invasion, and metastasis.

Genetic Considerations & Counselling

Genetics influences cancer at two levels:

• Somatic (tumor) mutations drive cancer growth.
• Germline (inherited) mutations increase lifetime cancer risk.

Common hereditary syndromes (NCBI)

• BRCA1/2: breast, ovarian, prostate, pancreatic cancers.
• Lynch syndrome (MLH1, MSH2, MSH6, PMS2): colorectal, endometrial, GI/urinary cancers.
• Others: TP53 (Li-Fraumeni), PTEN (Cowden), APC (FAP).

When to refer/test (NCCN)

• Early-onset (<50 yrs), multiple primaries, or strong family history.
• High-risk tumor types (e.g., high-grade ovarian, triple-negative breast).
• Always provide pre-test genetic counselling.

Counselling process (NCBI)

• Review family history & assess risk.
• Explain pros/cons of testing (positive, negative, VUS).
• Obtain informed consent; discuss implications.
• Offer cascade testing to relatives if a mutation is found.

Key patient points

• Positive result: changes screening or treatment; impacts relatives.
• Negative: lowers but may not eliminate risk.
• VUS: uncertain; managed by clinical history.
• Privacy: genetic discrimination laws (e.g., GINA) protect most health/employment cases.

Genetic Counselling (NCBI)

• Risk assessment: Review personal/family cancer history (who, what age).
• Discuss testing: Explain benefits, limits, and results — positive, negative, or VUS (uncertain).
• Informed consent: Cover medical, emotional, and insurance implications.
• Cascade testing: If a mutation is found, test at-risk relatives for prevention or early detection.

Key Points for Patients

• Positive result: May change screening, enable risk-reducing surgery, or guide targeted therapy; impacts relatives.
• Negative result: Usually lowers risk but doesn’t rule it out.
• VUS: Uncertain; managed by clinical/family history.
• Privacy: Laws (e.g., GINA) protect against most health/employment discrimination; discuss insurance concerns with counselor.

Cancer Management — Core Principles

Treatment is personalised based on cancer type, stage, molecular profile, and patient goals (curative vs. palliative).

1. Staging & Team Planning (PMC)

• Accurate staging defines treatment intent.
• Multidisciplinary teams (surgery, oncology, radiology, genetics, palliative care) coordinate care.

2. Local Therapy (Nature)

• Surgery: removes tumor (curative or debulking).
• Radiotherapy: controls local disease, can be curative, adjuvant, or palliative; sometimes combined with immunotherapy.

3. Systemic Therapy (PMC)

• Chemotherapy: kills rapidly dividing cells.
• Targeted therapy: blocks specific molecular changes (e.g., EGFR, PARP).
• Immunotherapy: boosts immune attack (e.g., checkpoint inhibitors, CAR-T).

4. Supportive Care & Survivorship

• Manage side effects, nutrition, and psychosocial issues; monitor for recurrence and late effects.

5. Palliative Care

• Focus on comfort and quality of life; integrate early for best outcomes.

Types of Cancer

Cancers are classified based on the type of cell or tissue from which they originate:

1. Carcinomas
   • Arise from epithelial cells (lining of organs, skin, glands).
   • Most common type.
   • Examples: breast, lung, colon, prostate, and skin cancers.
2. Sarcomas
   • Originate from connective or supportive tissue — bone, muscle, fat, cartilage.
   • Examples: osteosarcoma, liposarcoma.
3. Leukemias
   • Begin in blood-forming tissues like bone marrow.
   • Lead to excessive abnormal white blood cells circulating in blood.
4. Lymphomas
   • Develop in lymphatic tissues and immune system cells (lymphocytes).
   • Includes Hodgkin and non-Hodgkin lymphoma.
5. Central Nervous System Cancers
   • Originate in the brain or spinal cord.
   • Examples: gliomas, meningiomas.

Cell Mutations in Cancer

Cancer begins at the genetic level with mutations that disrupt normal cell function.

1. Types of Genetic Changes

• Oncogene activation: Normal genes (proto-oncogenes) that promote cell growth become permanently turned “on.”
  Example: RAS, HER2, EGFR.
• Tumor suppressor gene inactivation: Genes that normally control cell growth or trigger cell death become “switched off.”
  Example: TP53, RB1, BRCA1/2.
• DNA repair defects: Damage accumulates because DNA repair mechanisms (e.g., mismatch repair, BRCA pathway) fail.
• Epigenetic changes: Chemical modifications (e.g., DNA methylation) alter gene expression without changing DNA sequence.

2. Effects of Mutations

• Uncontrolled cell division
• Resistance to cell death (apoptosis)
• Evasion of immune surveillance
• Formation of new blood vessels (angiogenesis)
• Ability to invade and metastasize

Benign Tumour is a non-cancerous growth that remains localised, grows slowly, and does not invade nearby tissues or spread to other parts of the body.

Malignant Tumour is cancerous — it grows rapidly, invades surrounding tissues, and can spread (metastasize) to distant organs through the blood or lymphatic system. While benign tumours are usually not life-threatening, malignant tumours can cause serious harm or death if untreated.

 

Metastasis is the process by which cancer cells spread from the original (primary) tumour to other parts of the body. Cancer cells break away, travel through the blood or lymphatic system, and form new (secondary) tumours in distant organs such as the lungs, liver, brain, or bones. These secondary tumours have the same type of abnormal cells as the primary cancer. Metastasis is a key feature that distinguishes malignant cancers from benign tumours and often makes treatment more difficult.

 

Survival rates are usually reported as 5-year relative survival, which is the percentage of people alive 5 years after diagnosis compared to the general population.

Factors affecting survival:

• Cancer type and stage at diagnosis
• Age and overall health
• Response to treatment
• Access to healthcare and support systems

Example: Some cancers like thyroid or testicular cancer have high survival rates, while others like pancreatic or liver cancer tend to have lower survival rates.

Sickle Cell Disease is a genetic blood disorder characterised by the production of abnormal hemoglobin called S (HbS). This causes red blood cells (RBCs) to assume a crescent or sickle shape, especially under low oxygen conditions.

• Normal RBCs are flexible and round; sickled cells are rigid and sticky.
• These sickled cells can block blood flow, leading to pain, organ damage, and anemia.

Genetics of SCD

Inheritance Pattern

• SCD is autosomal recessive: a person must inherit two copies of the HbS gene (one from each parent) to have the disease.
• If a person inherits one HbS gene and one normal hemoglobin gene (HbA), they have sickle cell trait (carrier), usually asymptomatic.

Genetic Mechanism

• Mutation: A single nucleotide substitution in the β-globin gene (HBB) on chromosome 11:
  • DNA change: GAG → GTG
  • Amino acid change: Glutamic acid → Valine at position 6 of β-globin chain
• This produces HbS, which polymerizes under low oxygen, distorting RBCs into sickles.

History and Evolutionary Aspect

• First described in 1910 (Dr. James B. Herrick).
• Geographical prevalence: Common in Africa, India, Middle East, Mediterranean.
• Evolutionary reason: Heterozygous advantage—carriers of sickle cell trait (HbAS) have resistance to malaria, which is why the gene persisted in certain regions.

Transmission Across Generations

• Both parents must pass the HbS gene for a child to have SCD.
• Punnett square overview:
  • HbA + HbA → normal
  • HbA + HbS → carrier (trait)
  • HbS + HbS → sickle cell disease

 Signs and Symptoms (S/S)

SCD manifests due to anemia, hemolysis, and vaso-occlusion:

• Anemia: fatigue, pallor, jaundice
• Pain crises: acute episodes of severe pain due to blocked blood flow
• Swelling: hands and feet (dactylitis)
• Frequent infections: spleen dysfunction
• Delayed growth: due to chronic anemia
• Vision problems: retinal damage

 Diagnosis

• Newborn screening: Hemoglobin electrophoresis or HPLC (High-Performance Liquid Chromatography)
• Blood smear: shows sickle-shaped RBCs
• Genetic testing: confirms mutation in HBB gene
• Other labs: CBC, reticulocyte count, bilirubin levels

Treatment

• Supportive care: hydration, oxygen, pain management
• Medications:
  • Hydroxyurea: increases fetal hemoglobin (HbF) which reduces sickling
  • Pain medications: NSAIDs, opioids
  • Antibiotics & vaccines: prevent infections
• Blood transfusions: prevent stroke and manage severe anemia
• Bone marrow/stem cell transplant: only potential cure, mostly in children
• Gene therapy: emerging experimental treatment

Complications

• Acute: vaso-occlusive crises, acute chest syndrome, stroke, splenic sequestration
• Chronic: organ damage (kidneys, liver, heart), pulmonary hypertension, leg ulcers, retinopathy
• Infections: due to functional asplenia
• Shortened lifespan: if untreated, SCD can reduce life expectancy

End-of-Life Care (EOLC) – Last Days of Life
Care focused on comfort, dignity, and quality of life when death is imminent, rather than curing the disease.

Key Principles:

• Patient-centered: Respect wishes, values, and autonomy.
• Symptom management: Control pain, breathlessness, agitation, nausea.
• Emotional support: Reassure patient and family, address fear and anxiety.
• Family involvement: Provide guidance and support.
• Interdisciplinary approach: Doctors, nurses, social workers, spiritual care.

Common Signs of Imminent Death:

• Weakness, decreased appetite, and mobility
• Changes in breathing (e.g., irregular or shallow)
• Cool, mottled skin
• Decreased consciousness or unresponsiveness

Care Focus:

• Comfort measures: Pain relief (opioids), ease breathing, manage secretions
• Minimal interventions: Focus on comfort over nutrition or invasive treatments
• Communication: Honest, compassionate discussions
• Spiritual/cultural support: Respect rituals and practices
• Family support: Allow closure and guidance through grieving

Goal:
Ensure the patient dies comfortably, peacefully, and with dignity, while supporting loved ones.

KSBs addressed:

K1: Understand the Code: Professional standards of practice and behaviour for nurses, midwives and nursing associates (NMC, 2018), and how to fulfill all registration requirements

K4: Understand the principles of research and how research findings are used to inform evidence-based practice

K6: Understand and apply relevant legal, regulatory and governance requirements, policies, and ethical frameworks, including any mandatory reporting duties, to all areas of practice

S1: Act in accordance with the Code: Professional standards of practice and behaviour for nurses, midwives and nursing associates (NMC, 2018), and fulfil all registration requirements

S13: Apply the aims and principles of health promotion, protection and improvement and the prevention of ill health when engaging with people

S14: Promote preventive health behaviours and provide information to support people to make informed choices to improve their mental, physical, behavioural health and wellbeing

 

B1: Treat people with dignity, respecting individual’s diversity, beliefs, culture, needs, values, privacy and preferences

B2: Show respect and empathy for those you work with, have the courage to challenge areas of concern and work to evidence based best practice

B3: Be adaptable, reliable and consistent, show discretion, resilience and self-awareness

K41: Know the roles, responsibilities and scope of practice of different members of the nursing and interdisciplinary team, and own role within it

K42: Understand and apply the principles of human factors and environmental factors when working in teams

K43: Understand the influence of policy and political drivers that impact health and care provision Skills