Concise Flashcards Sem 2B

Question

Summarise the actions of different tumour supressors.

Answer 1

**Tumour Suppressors** 1. p21 2. p16 3. p53 4. pRB 5. p14ARF

Answer 2

**Cyclins DEAB** * Cyclin D → CDK4 or CDK6 * Cyclin E → CDK2 * Cyclin A → CDK2 * Cyclin B → CDK1

Answer 3

_Zones of the Prostate_ 1. **Peripheral zone (PZ)** * Most carcinomas originate here 2. **Central zone (CZ)** * Cancers here (2.5%) are more likely to invade seminal vesicles 3. **Transitional zone (TZ)** * Most hyperplasias originate here = BPH 4. **Periurethral zone** 5. **Fibromuscular** **stroma** (non-glandular)

Answer 4

**Pathogenesis of BPH** 1. Stromal cells produce 5α-reductase 2. 5α-reductase converts testosterone to dihydroxytestosterone (DHT) * DHT is ~10x as potent as testosterone 3. DHT stimulates transcription of growth factors by stromal cells (autocrine) and epithelial cells (paracrine) * Oestrogen also binds androgen receptors, enhancing the response 4. Hyperplastic stromal and epithelial tissues compress the prostatic urethra, leading to bladder outflow obstruction

Answer 5

**Symptoms of BPH** 1. Urinary frequency, urgency, hesitancy 2. Weak flow of urine, small volume voided 3. Nocturia 4. Interrupted stream 5. Incomplete bladder emptying 6. Dribbling

Answer 6

_Carcinogenic Agents_ * **Chemicals** - vinyl chloride, tobacco smoke (polycyclicaromatic hydrocarbons) * **Viruses** – HPV, hepatitis B, Epstein-Barr, herpes simplex * **Ionizing** (UV, X-rays, gamma rays) and non-ionising (α/β particles, neutrons, protons) radiation * Immediate effects – death, bone marrow failure, GIT effects * Late effects – leukaemia, thyroid cancer, lung/breast etc. cancer * **Exogenous** **hormones** – e.g. oestrogens in plastics * **Bacteria, fungi, and parasites** e.g. H. pylori * **Miscellaneous** agents (asbestos, metals)

Answer 7

**Urinary Casts** 1. Hyaline casts 2. Granular casts 3. Waxy casts 4. Fatty casts 5. Pigment casts 6. Crystal casts 7. RBC casts 8. WBC casts 9. Bacterial casts 10. Epithelial casts

Answer 8

_Causes of Tubulointerstitial Nephritis_ 1. **Infections** – pyelonephritis 2. **Toxins** – drugs, analgesics, heavy metals 3. **Metabolic** **diseases** – urate nephropathy, hypokalemic nephropathy 4. **Obstruction** – of urinary tract 5. **Neoplasms** – multiple myeloma 6. **Immune** **reactions**

Answer 9

_Glomerular Conditions - Clinical Presentation_ 1. **Nonspecific** → haematuria or polyuria 2. **Nephrotic** **syndrome**→ proteinuria, hypoalbuminaemia, hyperlipidaemia, lipiduria * Leakage of large amounts of protein due to increased glomerular permeability 3. **Nephritic** **syndrome** → proteinuria, haematuria, azotaemia, oliguria, hypertension, oedema * Leakage of protein and red blood cells due to renal inflammation 4. **Acute** **renal** **failure** - acute nephritis, proteinuria 5. **Chronic** **renal** **failure** - azotaemia → uraemia progressing for months to years

Answer 10

_Changes Essential for Malignant Growth_ 1. **Self**-**sufficiency** of growth signals (↑oncogenes) – mutations in growth factors, GF receptors, RAS, MYC, cyclins, CDKs 2. **Insensitivity** to growth-inhibitory signals (↓tumour suppressor genes) * BRCA1, BRCA2 (breast cancer) * APC (colorectal cancer) * p53 (many tumours) * Rb (retinoblastoma) * NF1 (neuofibromatosis) 3. **Evasion** **of** **apoptosis** – mutations in Bax, Bcl, caspases 4. Defects in **DNA repair** 5. Potential for **limitless** **replication** - e.g. maintenance of telomere length 6. **Angiogenesis** 7. **Invasion and metastasis**

Answer 11

_Haemostasis_ 1. **Vasoconstriction/Spasm** * Direct trauma (local myogenic spasm), chemical signals from damaged cells (e.g. TXA2 from platelets), nervous reflexes (from pain impulses and sensory inputs) 2. **Platelet Plug Formation** 1. Adhesion: platelets bind to exposed collagen – aided by vWF (platelets) 2. Activation: by exposed collagen - activated platelets secrete ADP and TXA2 3. Aggregation onto the growing platelet plug 3. **Blood Coagulation – The Clotting Cascade** * Prothr. activator catalyses prothrombin → thrombin - catalyses fibrinogen → fibrin 4. **Restoration of Normal Bloodflow** * Clot lysed by Fibrinolysis - Plasminogen → plasmin → catalyses breakdown of fibrin

Answer 12

_Endogenous Substances that Limit Coagulation_ 1. **Antithrombin III** (ATIII) – binds to activated clotting factors (IIa, IXa, XIa, XIIa) and inactivates them – heparin increases ATIII activity 2. **Activated Protein C** (APC) – activated by thrombin - inactivates factors V and VIII 3. **Protein S** – cofactor for protein C on platelet surface

Answer 13

**Disorders of Haemostasis** 1. Vessel Wall Abnormalities 2. Platelet Deficiency (thrombocytopenia) 3. Defective Platelet Function 4. Abnormalities in Clotting Factors

Answer 14

**_Disseminated Intravascular Coagulation (DIC)_** **Summary** * Excessive activation of coagulation, leading to formation of thrombi in the microvasculature * Occurs as a secondary complication of many different disorders * Presents with signs and symptoms related to tissue hypoxia/infarction or haemorrhage **Pathogenesis** 1. Release of tissue factor or thromboplastic substances into the circulation, or 2. Widespread injury to endothelial cells

Answer 15

_Types of Lymphoid Neoplasms_ 1. **Lymphoid** **Neoplasms** – the phenotype of the neoplastic cell resembles a stage of lymphocyte differentiation * **Acute** **lymphoblastic** **leukaemia** (ALL): proliferation of pre-B/T cells * **Chronic** **lymphocytic** **leukaemia** (CLL): proliferation of B cells * **Lymphoma**: proliferation of B/T/NK cells in tissues 2. **Myeloid** **Neoplasms** – arise from haematopoietic stem cells that differentiate into myeloid lineages * **Acute myeloid leukaemia** (AML): accumulation of immature progenitor cells in bone marrow * **Myelodysplastic syndromes** : due to ineffective haematopoiesis * **Chronic myeloid leukaemia** (CML): accumulation of terminally differentiated myeloid cells 3. **Histiocytoses** – proliferative lesions of macrophages and dendritic cells

Answer 16

_Major Types of Leukemia - Prognosis_ 1. **Acute Lymphoblastic** - ~95% of children will achieve full remission with aggressive chemotherapy, and ~80% are cured 2. **Chronic** **Lymphoblastic** - extremely variable, median survival is 4-6 years 3. **Acute** **Myelogenous** - difficult to treat, 60% of patients achieve full remission using chemotherapy, but only ~20% remain disease-free for 5 years 4. **Chronic** **Myelogenous** - insidious onset and slow-progressing disease, without treatment, the median survival is 3 years * Allogenic bone marrow transplantation in young patients is curative in 75% of cases

Answer 17

**Purine Metabolism**

Answer 18

**Pyramidine Metabolism**

Answer 19

_Chemotherapy - Side effects_ * **Bone** **Marrow**: myelosuppression * Leukopenia, lymphocytopenia, thrombocytopenia, anaemia * Increased risk of infection * Impaired wound healing, haemorrhage * **GIT**: oral/intestinal ulceration → nausea, vomiting, diarrhoea * **Hair** **roots**: alopecia * **Gonads**: menstrual irregularities, amenorrhoea, infertility * **Any** **tissue**: predisposition to future cancer (disruption of DNA) * **Foetus**: teratogenesis

Answer 20

_Overcoming Limitations of Chemotherapy_ 1. **Toxicity** * Most drugs are cytotoxic – kill normal cells as well as cancer cells 2. **Resistance** * Inability of tumour cells to undergo apoptosis in response to drug-mediated DNA damage * Alteration of the drug target, ↑expression of the drug target, ↑rate of repair following damage * ↓ drug uptake, ↑ drug efflux/clearance, ↓ activation of prodrug

Answer 21

**Difficulties faced by a rural doctor** * Being the ‘outsider’ when entering into the community – local rules * Isolation * Difficult for spouse & children – lack of family support, difficulty in making friends * Often a low standard of working environment * Extended on-call period * Boundaries between personal and professional relationships may become blurred

Answer 22

_Rural Barriers to Healthcare_ 1. **Decreased** **access** to healthcare * Geographical remoteness * Limited resources (e.g. imaging/pathology) * Lower proportion of people with private healthcare * Difficulty attracting local specialists * Shortage of nursing homes 2. **Lower socioeconomic status** 3. **Harsher environments** 4. **Sparse** **infrastructure** 5. **Poor** **uptake** of health promotion messages 6. Increased **occupational hazards** 7. Attitudes towards safety and more frequent indulgences in **risky behaviour**

Answer 23

**Path of Milk** 1. Alveoli 2. Intralobular ducts 3. Terminal interlobular ducts 4. Lactiferous ducts 5. Lactiferous sinuses

Answer 24

1. Pectoralis major 2. Pectoralis minor 3. Parts of serratus anterior 4. External oblique

Answer 25

**Lymphatic Drainage of the Breast.** * Lateral: anterior axillary nodes (75%) * Medial: parasternal nodes

Answer 26

**Mammary Gland**

Answer 27

_Hormonal Control of Mammogenesis_ 1. **Growth and branching of the ductal system and stroma is stimulated by:** * Oestrogen * Growth hormone * Prolactin * Insulin * hCG * Placental lactogens (hCS) 2. **Development of alveolar tissue is stimulated by progesterone** * Synergised by oestrogen and other hormones 3. **Prolactin levels are increased** * Prolactin stimulates milk production * This is inhibited by oestrogen and progesterone until after parturition

Answer 28

**Menopause** 1. Reduction in size of breasts and uterus 2. Mood changes, anxiety, depression 3. Hot flashes – intense heat, sweating, tachycardia 4. ↑risk of cardiovascular disease 5. Memory loss – anecdotal but no studies 6. Vaginal dryness 7. Dry skin 8. Insomnia 9. Fatigue 10. ↑ risk of osteoporosis

Answer 29

_Triple Assessment of Breast Cancer Diagnosis_ 1. **Clinical** – inspection and palpation 2. **Radiological** – mammography, ultrasound, CT 3. **Pathological** – fine needle aspiration, histological assessment Sensitivity: 99.6% Specificity: 62%

Answer 30

_Breast Cancer - Risk Factors_ 1. **Gender** – 99% of cases occur in women (1% in men) 2. **Age** – peaking at 75-80 years 3. **Age** **at** **menarche** – menarche at 11 years old → 20% increased risk 4. **Age** **at** **1st** **live** **birth** - giving birth \<20 years → 1/2 risk vs. nulliparous 5. **First-degree relatives with breast cancer** 6. **History of atypical hyperplasia** 7. **Race** – risk of developing invasive carcinoma in the next 20 years: * Non-hispanic white women 1 in 15, African Americans: 1 in 20, Asian/Pacific islanders: 1 in 26, Hispanics: 1 in 27 8. **Estrogen** **exposure** – postmenopausal hormone therapy (↑risk by ~1.5) 9. **Breast** **density** – high breast radiodensity 10. **Radiation** **exposure** – cancer therapy, atomic bomb, nuclear accidents 11. Carcinoma of contralateral breast or endometrium 12. **Geographic** – rates in the USA and Europe 4-7x higher than other areas 13. **Obesity** – ↓ risk in obesity; ↑ risk with postmenopausal obesity 14. **Not** **breastfeeding** – the longer a woman breastfeeds the lower the risk

Answer 31

**Histological Subtype of Breast Cancer** 1. In situ ductal carcinoma (DCIS) 2. In situ lobular carcinoma (LCIS) 3. Invasive ductal cancer 4. Invasive lobular cancer 5. Other invasive cancer

Answer 32

_Treatments for ER+ (oestrogen receptor positive) cancers_ 1. **Selective Oestrogen Receptor Modulators** (SERMS) * Tamoxifen * Raloxifene * Selectively antagonise/agonise E receptors → ↓ growt 2. **LHRH agonists (GNRH agonists)** * ↓ LH and FSH → ↓oestrogen * Effective in premenopausal women 3. **Selective aromatase inhibitors (steroidal/non-steroidal)**

Answer 33

_Prognostic Indicators for Breast Cancer_ 1. **Invasive vs. In situ** * The majority of women with DCIS are cured 2. **Distant** **metastasis** – cure is unlikely, but long-term remissions are possible 3. **Lymph** **node** **metastasis** – the most important diagnostic factor * No nodal involvement – 10-year survival rate is 70%-80% * 1-3 nodes involved – 35-40% * \>10 nodes involved – 10-15% 4. **Tumour size** 5. **Locally** **advanced** **disease** – into skin or skeletal muscle 6. **Inflammatory carcinoma** – breast swelling and skin thickening * 3-year survival rate is only ~3-10%

Answer 34

_Strategy for Breaking Bad News = SPIKES_ * **S – Setting** → Basic communication and facilitation skills, be available, ensure privacy, involve significant others – e.g. family, close friends * **P – Perception** → Ask the patient what they already know or suspect, determine the patient’s perception of the seriousness of the situation as well as their comprehension * **I – Invitation** → Obtain a clear invitation to share information; determine the level of detail the patient wants, leave option to request information open * **K – Knowledge** → Warn that bad news is coming, start at the same level of the patient’s comprehension, give information in small chunks, check that content is understood * **E – Empathy** → Identify emotion/cause of emotion, respond to show a connection has been made * **S – Strategy and Summary** → Summarise major points, ensure that patient understands Strategise – make a clear contract for the next meeting

Answer 35

**Classical Conditioning** * A neutral conditioned stimulus is repeatedly paired with an unconditioned stimulus which invokes a conditioned response * Over repeated trials the neutral stimulus eventually evokes a similar response * E.g. Pavlov’s dog – the sound of footsteps (CS) began to evoke salivation (CR) in dogs anticipating food (UCS)

Answer 36

_Operant Conditioning_ * Actions which result in reinforcement are strengthened and more likely to occur * **Positive** **reinforcement** – e.g. more parental attention with symptoms of anxiety * **Negative** **reinforcement** – removal of a negative stimulus e.g. avoiding school to avoid bullying * Actions which result in punishment are weakened and less likely to occur * **Punishment** – presentation of a negative stimulus * **Negative** **punishment** – removal of a reinforcer e.g. removing pocket money

Answer 37

**Morbidity & Mortality - Young People** * Mental health problems are the major burden of disease (50%) in young people * Primarily anxiety disorders * Affective disorders * Substance abuse disorders * Injury is the leading cause of death (2/3) * Suicide (27%) * Transport accidents (45%)

Answer 38

Changes that occur during adolescence: * Peers and Parents * Autonomy * Education & Vocation * Sexuality * Body image & identity

Answer 39

**Anxiety - Clinical Features** 1. Cognitive experience of dread 2. Associated physiological changes 3. Behavioural attempts to escape or avoid

Answer 40

_Cognitive & Behavioural Manifestations of Anxiety_ * **Hypervigilance** – rapid and global scanning for threats * If a threat is detected, the anxious person’s attention focuses narrowly and intensely on it * **Selective** **attention** – narrowing of attention that occurs in response to a threat * External e.g. lightning – someone with a storm phobia will constantly watch the skies * Internal e.g. heart beat – someone with hypochondriasis will pay close attention for skipped beats * Excessive self-focus is the basis for abnormal behaviour and experience * Alcohol inhibits self-focussing – can reduce anxiety in social situations * **Avoidance Behaviour** * Initially, intense relief with avoidance of a feared situation - reinforcing * In the long term, avoidance strengthens the belief and maintains the anxiety

Answer 41

**Physiological Manifestations of Anxiety** 1. Dizziness 2. Confusion – impairment of concentration, new learning, recall 3. Syncope 4. Hyperreflexia (twitching) 5. Tremors; restlessness 6. Diarrhoea, upset stomach 7. Pupillary mydriasis 8. Tachycardia; palpitations 9. Hyperhidrosis (excess sweating) 10. Hypertension 11. Urinary frequency, hesitancy, urgency

Answer 42

**OCD - Diagnostic Criteria** 1. Presence of obsessions (pervasive and intrusive thoughts, impulses, images) and/or compulsions (repetitive behaviours or mental acts that must be applied rigidly) 2. The person must realise that the obsession and/or compulsions are excessive and unreasonable 3. The obsessions and/or compulsions cause marked distress, are time consuming (\>1hour/day), or significantly interfere with day‐to‐day functioning

Answer 43

_Anxiety - Pharmacological Treatment Options_ 1. **Antidepressants** * Selective serotonin reuptake inhibitors (SSRIs) * Tricyclic antidepressants (TCA) 2. **Anxiolytic Drugs** * Benzodiazepines * Azapirone * Beta-blockers 3. **Anticonvulsant** **drugs** * Valproate * Gabapentin 4. **Atypical** **antipsychotic** **drugs** * Risperidone * Olanzapine

Answer 44

_Anxiety - Non-pharmacological Treatments_ 1. **Relaxation, Breathing Training, Mindfulness** - deep breathing, progressive muscle relaxation, imagery, hyperventilation control, mindfulness 2. **Exposure** **Therapy** - gradually exposing patients to identical or similar stimuli to what he/she fears, to habituate the patient to the stimulus 3. **Systematic** **Desensitisation** - exposure therapy & relaxation training 4. **Cognitive‐Behavioural Therapy** - focuses on information processing, learning and problem solving by identifying automatic thoughts and core beliefs associated with anxiety, then challenging and restructuring unhelpful thoughts and beliefs * What’s the worst thing that could happen? How likely is it that it will happen? What’s an alternative explanation? 5. **Social** **interventions** - managing stress, friendships & supports, relaxing activities 6. **Diet** - avoid alcohol, caffeine, illicit substances, foods with preservatives, medications with pseudoephedrine (where practical)

Answer 45

**Gillick's Ratio** A minor can consent to medical treatment once s/he has achieved a “sufficient understanding and intelligence to enable him or her to understand fully what is proposed”.

Answer 46

_Profile of a Resilient Child_ 1. **Social competence** * Responsiveness o Flexibility * Empathy * Caring * Communication skills * Sense of humour 2. **Problem solving skills** * Critical thinking * Generating alternatives * Planning * Producing change 3. **Autonomy** * Self-esteem * Self-efficacy * Independence * Adaptive/healthy distancing 4. **Sense of Purpose and Future** * Goal directedness * High motivation * Educational aspiration * Persistence * Hopefulness * Coherence