EMQs

EMQ CHRISTMAS 2008 1. Anaemia 2. STI 3. NMJ / AP 4. NTD + Trisomy 21 5. Pharm COX 6. Pharm 7. O2 dissociation curve 8. Neoplasia terms 9. Ear anatomy 10. Skin histology 11. Wrist anatomy falling on outstretched arm etc EMQ SUMMER 2009 1. Stats PPV etc 2. Stats CI 3. Pharm ABs 4. Pharm cardiac drugs 5. STIs 6. Ulcers 7. Muscle fibers chain, bag, alpha and beta 8. Lymph little finger, gonads 9. Knee ligaments 10. Anatomy of back S2,3,4 11. Osmolality / compartments decrease BV, burns etc 12. Ear anatomy 13. Hernia anatomy 14. Cranial nerves 15. Pain 16. Exercise 17. Bile 18. Cancer xeroderma pigmentosum 19. Ethics 20. Bile EMQ REPEAT AUGUST 2009 1. Female perineum 2. Surface anatomy lungs 3. Male testes 4. Liver lobule structure 5. Stomach / liver / kidney ligaments / omentum 6. Muscles of gait eccentric / concentric hip, knee, ankle 7. Fetal circulation liver bypass, apoptosis primum, secundum, deoxy perineum -> mother; umbilical artery, foramen ovale 8. Bacteria parts wall etc 9. Anemia types ulcer (dark stools), pernicious, macrocytic, chemo, sickle cell 10. Diabetic complications erection, glove and stocking neuropathy, joint (swollen + pain) 11. Hypo pit hormones 12. Reproduction hormones temp increase 13. Parts of CNS eye afferent accommodation efferent hand off hot stove mid brain / hind tachycardia, hypotension cerebral cortex, cerebellum 14. Cells in inflammation etc 15. Nerve injures umbilicus level, herpes, ptosis, miosis, wasting intrinsic hand muscles 16. Cranial nerves 17. Headache 18. ECG ventricle depolarization Purkinje fibbers 19. Rheumatology drugs Reyes (encephalopathy), folate, ocular problems 20. Stats P values, incidence 1. 2. 3. EMQ Christmas 2009 (1st year Class of 2013) Ear anatomy and physiology Anaemia different types Biostats data distribution (skewed, uniform, symmetrical etc)

4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20.

Biostats different types of clinical trials Immuology types of cells - WBCs mainly I think Immunology cells, chemical mediators etc Immunology more of the same, also inc tissue types involved eg ciliated epithelium etc Antibiotics indications, interactions etc Karyotypes Downs, Trisomy, 47XXY, 45X, 46XY etc Birth defects meningocele, meningoencephalocoele, Arnold-Chiari malformation etc STIs symptoms Neoplasia tumour types eg papilloma, leiomyoma, benign, malignant Partial pressures of O2, CO2 and N2 in tissues, blood vessels, alveoli and mitrochondria! Contraception Action potential, Nerve synapse, NMJ which voltage-gated, ligand-gated ion channels opened or closed at different stages Bacteria structure Osteoporosis Infertility/Fertility PCOS, Ectopic pregnancy, Turners syndrome Actions of male and female sex hormones ?? possibly another immunology!

SAQs
SAQ CHRISTMAS 2008 1. ETHICS AUTONOMY Helen has been diagnosed as having Otosclerosis. Dr Jarman explains that surgery is a possible treatment in some cases. Helen tells Dr Jarman that she will be consulting her naturopath because he has cured a lot of conditions that conventional medicine cant touch. a. Helen is exercising her autonomy in consulting a naturopath. What is meant by autonomy in medical ethics (3 marks) b. Where do doctors find guidance on how to ensure respect for patient autonomy in clinical practice? (2 marks) c. Explain briefly, with reference to your definition of ethical principal of autonomy how Dr Jarman should respond to Helen.

Autonomy

Autonomy: the basic idea of personal autonomy is that everyones actions and decisions are their own. Therefore the patient has the right to decide what happens to their own body. In order to exercise autonomy, a person should be an adult and of sound mind. Article 40.3 of the Irish Constition protects the right to self determination, bodily integrity and privacy. Medical Counsel Guidelines 2009. Hippocratic oath o o

Guidance:

Beneficence: Do good, what's in the best interests of the patient. Nonmaleficence: Don't be bold. Don't hurt the patient. (Where do you draw the line? Euthanasia in terminal illness? Injections hurt, right?) Justice: Making the best use of resources possible. Don't give all the care to the rich people etc. Autonomy

o o

How to respond:

Every adult with capacity is entitled to refuse medical treatment. You must respect a patients decision to refuse treatment, even if you disagree with that decision. In these circumstances, you should clearly explain to the patient the possible consequences of refusing treatment and offer the patient the possible consequences of refusing treatment and offer the patient the opportunity to receive a second medical opinion if possible. The explanation you give the patient and the patients refusal should be clearly documented in the patients medical records.

2. Anatomy female pelvic viscera VISCERA=Grand. 3. Osteoporosis Mary 80 year old with osteoporosis a. Outline the changes which occur in bone with osteoporosis decrease in bone density / loss of bone mass; increase fragility / risk of fractures b. In addition to her age, give 3 risk factors which GP should ask about smoking; steroid use; low BMI; family hx; premature menopause, hyperparathyroidism c. Referred for investigation found to have T score of -2.6. What investigation? DEXA d. Explain T-score of 2.6 e. 2 rx that would be appropriate for Mary biphosphates; calcium and vitamin D supplements 4. Stats definitions 5. 6. 7.

1. Stats definitions a. Double blind technique

Neither the patients, the experimenter, nor any of the assessors of the results, knows which participants are subject to which procedure (or took which treatment etc). This helps to ensure and biases or expectations will not influence results 8. b. Assessment bias When patients and/or clinicians are aware of the treatment allocation, particularly if the response is subjective. An awareness of treatment allocation may influence the recording of signs of improvements or adverse events. Therfore, where possible, all participants (clinicans, patients, assessors) in a trial should be blinded or masked to the treatment allocation. 10. c. Random allocation of patients
9. 11. 12. 13.

When patients are randomly allocated to one of two independent groups d. Wash out period

This arises in a cross-over trial. The patients will receive 2 treatments (eg. half will receive new treatment followed by control and half will receive control treatment followed by new tx. The wash-out period is the amount of time that has to be left between treatments so that the first treatment is no longer in the patients system In the absence of a wash-out period, a positive or negative effect could be wrongly attributed to the second tx. 14. e. Confounding bias
15.

When a spurious association arises due to a failure to adjust fully for factors related to both the risk factor and the ourcome
Likelihood ratios

a) The likelihood ratio for a positive result is the likelihood of a patient who has been clinically diagnosed as having a disease having a positive result according to a screening test (i.e. effectiveness of the test at indentifying true positives), compared to the likelihood of a patient who does not a disease having a positive result according to the screening test (i.e. false positive rate with CAGE).

The formula for this is (Sensitivity) / (1 Specificity)

b) The likelihood ratio for a negative result is the likelihood of a patient who has been clinically diagnosed as having a disease having a negative result according to the screening test (i.e. false negative rate with the screening test), compared to the likelihood of a patient who has been clinically diagnosed as not having a disease having a negative result according to the screening test (i.e. effectiveness of the screening test at identifying true negatives).

The formula for this is (1 - Sensitivity) / Specificity 16.Michael Jackson (see sample questions) a. Explain briefly why lack of O2 leads to brainstem death b. Explain why heart is less seriously affected by hypoxia than brain. c. Explain in 4 sentences why O2 is needed. 17.Anatomy lungs surface anatomy etc. SAQ SUMMER 1. PARKINSONS a. What is deficient? - Da b. Precursor and amino acid in vivo precursor levodopa (L-DOPA); amino acid = tyrosine c. 2 enzymes, which metabolize px deficient neurotransmitter and are therapeutic agents in PD? MAO-B = selegiline; COMT - Entacapone d. More powerful drug: L-DOPA with dopa decarboxylase inhibitor and dopamine agonist (eg Ropinirole). e. Explain what factors should be taken into account in choosing between these 2 options for px tx with reference to relative efficacy and adverse affects of 2 drugs classes you have chosen? Both L-DOPA and ropinirole cause nausea vomiting and psychiatric symptoms such as vivid dreams, hallucinations etc. and also postural hypotension. L-DOPA was the usual first line treatment, but there are some issues: at first there can be dyskinesias from over medication until the correct dosage can be determined. Then, long-term there can be a shortened duration of action of each dose and symptoms can develop between doses. (basically it becomes less effective). Ropinirole is good for newly diagnosed you patients starting therapy as there are less motor fluctuations and dyskinesias. It is also good for advanced patients who are experiencing symptoms between doses of L-DOPA; it may allow them to reduce their dose of L-DOPA. 2. NTD from sample questions 3. COPD AND EMPHYSEMA a. Define COPD b. Pathophysiology of cor pulmonale c. FEV1 (54%) FVC (70%) explain abnormalities

d. e.

Define COPD: Obstructive pulmonary diseases cause difficulty in expelling air from the lungs,. Chronic obstructive pulmonary disease (COPD) is a term which denotes a group of chronic conditions associated with lung tissue damage and airflow obstruction with little or no reversibility. These chronic conditions are classified according to the clinical features (chronic bronchitis, chronic asthma), their chronic pathological changes (emphysema) or physiological correlates (pink puffers, blue bloaters). As these diseases often coexist and overlap, one term is used to describe them, which is COPD. Pathophysiology of Cor Pulmonale: Mechanism: 1. Pulmonary hypertension * 2. Increased workload (afterload ) for RHS of heart 3. Leads to right heart failure. *COPD causes pulmonary hypertension by several mechanisms: 1. Loss of capillary beds (eg, due to bullous changes in COPD) 2. Vasoconstriction caused by hypoxia, hypercapnia, or both 3. Increased alveolar pressure (eg, in COPD, during mechanical ventilation) Demands on the RV may be intensified by increased blood viscosity due to hypoxia-induced polycythemia. Explain abnormalities: FEV1 measures the forced expiratory volume in 1 second. FEV1 = 54% Reason: In emphysema the lung is less compliant and cannot expire air as easily. In chronic bronchitis there are blockages in the airways due to excess secretion of mucus/inflammation and thus air cannot be exhaled easily. FVC is a measure of the maximum amount of air that you can blow out of your lungs voluntarily. FVC = 70% Reason: It is may be reduced in COPD patients due to damage of the lung tissue/small airways. In general FVC is not affected as much as the FEV1- it just takes time and effort for them to remove the trapped air. FEV1/FVC ratio less than 70% = obstructive disease

f. g. h. i. j. k. l. m. n. o. p. q. r. s.

t. u. v.

w.

4. CANCER a. Oncogene and tumor suppressor gene b. Name 2 cell cycle enzyme checkpoints P53, ATM c. 2 physical oncogenes lead; XR, asbestos, coal tar, alcohol d. UV damage to DNA UVB light causes thiamine dimers direct DNA damage; UVA light creates free radicals indirect DNA damage e. Why is cancer a disease of the old? f. Breast cancer genes BRCA 1, BRCA 2 g. 2 viruses that cause cancer HPV, EBC, HBV, HCV, HHV8 5. PITUITARY HORMONES

a. b. c. d. e.

4 anterior pituitary hormones Regulation of secretion 2 hormones involved in water and salt balance and how they work 4 hormones give young boy with Hypopituitarism and hypogonadism Draw optic chiasm LH, GH, TSH, ACTH (+FSH, Prolactin)

a. 4 anterior pituitary hormones b. Regulation of secretion Controlled by hypophysiotropic hormones released by hypothalamus. All stimulate secretion (exception DA which inhibits and GH which can stimulate or inhibit). -ve feedback loops control secretion high circulating levels trigger hypothalamus and pituitary to stop production. c. 2 hormones involved in water and salt balance and how they work ADH and aldosterone ADH (vasopressin) released by posterior pituitary increases aquaporin channels in collecting ducts increased H20 reabsorption. Aldosterone increases Na and H20 reabsorption in cortical collecting ducts Renin Angiotensin system: low blood volume juxtaglomerular apparatus increase rennin secretion angiotensin II adrenal cortex aldosterone. d. 4 hormones give young boy with Hypopituitarism and hypogonadism GH normal growth: acts on liver to produce IGF-1; protein anabolism; protein synthesis; CHO and lipid metabolism. LH act on Leydig cells to secrete testosterone (male 2 sexual characteristics) ACTH acts on adrenal cortex (zona fasiculata) to produce glucorticoids TSH acts on thyroid gland to produce thryoxine and triiodothyronine. Involved in controlling the metabolic rate and influencing physical development. e. Draw optic chiasm

6. SHOULDER ANATOMY SAQ REPEAT AUGUST 2009 1. HB STRUCTURE a. Briefly describe the quaternary structure of normal HbA. - 2 alpha and 2 beta chains - haem group attached to each of 4 chains - Ferrous iron attached to each of 4 chains - H20 molecule attached to each of 4 Fe atoms in deoxy Hb b. Describe the non-covalent forces stabilizing the quaternary structure of Hb. - Ionic bonds - Hydrogen bonds - Van der waals forces - Hydrophobic interactions - Dipole dipole interactions c. What happens to Hb on oxygenation? Why is this effect sometimes described as cooperative? - Relaxed taut cooperative facilitates binding. d. Speculate why amino acids substitution observed in Chaturis Hb causes decreased affinity for O2. How does it differ in fetal Hb? - Intro of more positive charged amino acid in place of negatively charge one in Beta chain means that highly negative charged allosteric effector 2-3 BPG binds even more strongly to Hb beta chains stabilizing deoxy form of Hb - Opposite situation to that in HbF where gamma chains are present rather than Beta chains gamma chains higher affinity for O2 because decreased positive charge in gamma chains making 2-3 BPG bind less readily => stabilizing oxy form of Hb. 2. CVA a. List 2 different types of vascular accident caused by CVA - Ischemic / haemorrhagic b. Risk factors that should be identified and / or treated in px with CVA

- HTN, high cholesterol, alcohol, hyperglycemia c. 2 medications used for secondary prevention and mode of action - Aspirin, Clopidogrel, ticlopidine Antiplatelet d. Structures of circle of Willis 3. DOWN SYNDROME 3. DOWN SYNDROME a. Define karyotype (1) Karyotype a photo representation of a stained metaphase in which the chromosomes are numbered in order of decreasing length characterization of the chromosomal complement - including number, form, and size of the chromosomes. b. Outline normal phases of meiosis (3) Interphase G1 cell grows; S cell copies chromosome; G2 cell grows, prepare for division; M cell division Meiosis I Prophase I duplicate chromosome sister chromatids in pairs = homologous chromosomes o (different from Mitosis, which is pairs of chromosomes each pair = a sister chromatid) o crossing over occurs homologous chromosomes attached at random points called chiasmata Metaphase I pairs of sister chromatids line up at midline attached to spindles Anaphase I pairs of sister chromatids get pulled apart by spindles to opposite poles Telophase I cell divides, each cell with a sister chromatid Meiosis II Prophase II no duplication chromosomes already in pairs Metaphase II sister chromatids line up at midline Anaphase II sister chromatids separate into individual chromosomes Telophase II cell divides, each cell with a chromosome c. How does error in one phase cause DS (2) Non-disjunction chromosome or chromatid fail to separate either in meiosis I or II 14/21 Robertsonian translocation d. What does geneticist mean by Robertsonian translocation? (2) Robertsonian translocation two acrocentric chromosomes join and the short arm is lost 14/21 Robertsonian translocation

e. What is risk of recurrence if mother / father is carrier? If mom has Robertsonian translocation 1:8 If dad has Robertsonian translocation 1:50 4. HOMEOSTASIS Describe the homeostatic mechanisms that will be activated in different bodily organs and systems in an attempt to conserve water. a. b. c. d. Brain Vascular Kidney Endocrine

A) Brain: Central osmoreceptors are present in the hypothalamus. When concentration of the plasma changes, the diffusion of water into and out of the osmoreceptor cells change. For example, with a net loss of water, plasma becomes concentrated, taking water out of the osmoreceptor cells via an osmotic shift. The osmoreceptors, despite being in the hypothalamus, are not covered by the blood-brain-barrier (this is necessary for them to fulfill their duty). The exact parts of the hypothalamus they are in are called the organum vasculosum or the lamina terminalis (OVLT) and the subfornical organ (SFO). These osmoreceptors evoke the feeling of thirst. Increased intake of water will increase plasma volume. There are different osmoreceptors in the same area (OVLT and SFO of the hypothalamus) that do not contribute to the experience of thirst, but rather activate the release of Vasopressin to decrease fluid output. (More about this in the endocrine section.) Side note: this is also why salty foods increase thirst. Excess salt in the bloodstream saps water from the osmoreceptor cells, via osmosis, just like when there was a deficit in water. The end result is the same: you get thirsty. B) Vascular: Vascular control is exerted by the cardiovascular baroreceptors. A drop in plasma volume due to water loss will cause these baroreceptors to signal the posterior pituitary to increase vasopressin secretion. Vasopressin will then act on the collecting ducts to increase tubular permeability to H20 and thus increase reabsorption of water. The reflex is initiated by baroreceptors which decrease their rate of firing when cardiovascular pressure decreases. Vasopressin also causes widespread vasoconstriction-helping to restore blood pressure to normal. (recall, a pressor drug is one that increases blood pressure. Vasopressin, its in the name.) C) Kidney A drop in arterial pressure causes less stretch of renal juxtaglomerular cells, and a drop in plasma volume decreases the GFR, leading to decreased flow to the macula densa. This in turn leads to decreased NaCl delivery to macula densa. The renal juxtaglomerular cells then increase renin secretion, which acts via the Renin-AldosteroneAngiotensin system to increase blood pressure (angiotensin tenses the arteries) and increase sodium and water reabsorption (aldosterone). Aldosterone acts at the DCT and collecting ducts, and also increases secretion of potassium. D) Endocrine: Endocrine efforts to conserve water are due largely to vasopressin and aldosterone, and thus overlap with what was discussed earlier. 1) Vasopressin: Also called antidiuretic hormone (ADH)- comes from the posterior pituitary. It increases osmolality of urine/concentrates urine and decreases excretion of water. It stimulates the insertion of water channels (aquaporin 2) into the apical membrane of the Distal Convoluted Tubule and Collecting ducts, allowing increased reuptake of water. It also stimulates the Na2/K/Cl- cotransporter in the ascending loop of henle, causing increased reabsorption of NaCl, which drives countercurrent multiplication and creates the osmotic gradient needed for the reabsorption of water. 2) Aldosterone: Acts on nuclear mineralocorticoid receptors in the cells of the distal tubule and collecting duct of nephron. It affects transcriptional changes typical of steroid hormone action, resulting in the upregulation of the Epithelial Sodium Channel (ENaC). This channel increases the permeability of the nephron to sodium. Aldosterone stimulates the active reabsorption of sodium from the tubular urine back into the nearby capillaries in the distal tubule. Water is passively reabsorbed with sodium which maintains sodium concentrations at a constant level. It also stimulates the secretion of potassium. 5. SHOCK 25 yo male RR 34 / min Pulse oximetry 95% on 15l / min HR 140 / min BP 79 / 48 Conscious, confused; open eyes to vocal stimuli and following simple commands 15cm laceration on leg

a. b. c.

d.

- Shock due to blood loss 2 14 gauge IV cannula - Gives 1L Hartmans solution crystalloid - After infusions, BP increases 96/64 What is shock and how is it classified? - State where CO insufficient to meet metabolic demands of body - Hypovolaemic, septic, neurogenic, cytotoxic, cardiogenic, anaphylactic How much blood lost? Justify - At least 40% circulating volume 2 liters - Not until this degree of blood loss would a young fit px become hypotensive What is the immediate physiological response to blood loss? How does it account for patients clinical signs? - Decrease BP baroreceptors in aortic arch and carotid sinus, increase symp activity vasoconstriction (pallor and cold extremities); blood flow to vital organs, increase HR and contractility, tachycardia - Hypotension and confusion are due to blood loss being so large that these mechanisms are not able to compensate and maintain good CNS perfusion Explain in physiological terms how infused fluid causes increase in BP - Increase in intravascular volume cases increase in venous return => Increase LVEDV -> starlings law increase SV and CO; CO = SV x HR; BP raises as product of CO and TPR; MAP = CO x TPR

6. VIRUSES a. Structure of Herpes virus (3 marks) - Electron dense core of DNA - Capsid surrounding core - Tegument surrounding capsid b. Replication cycle of virus (4 marks) c. 2 methods used in diagnosis of HSV (2 marks) - Virus culture - Culture followed by immunoflourescence determine virus type - Polymerase chain reaction amplification of viral DNA d. How contracted? (1 mark) -Skin contact -Sexual contact Class of 2011: 1st Year (2007/2008): Q1: Depression risk factors and suicide risk factors Q2: Rheumatoid arthritis - treatment and pathogenesis Q3: Heart disease - Risk factors for MI and treatments and atherosclerosis pathogenesis Q4: Downs syndrome - what is mosaicism and risk of offspring having it Q5: Cancer - what causes it and two viruses, and types Q6: Shock different types and Circle of Willis multiple-choice picture 2nd Year Christmas exams (2008/2009) Q1: CT abdomen and steattorrhea Q2: Menorrhagia and period pain / menstrual cycle Q3: Marathon runner muscles; weight vs. endurance; muscle fibre contraction - coupling Q4: Stats - drug efficacy Q5: ECG and some question about MI heart failure? Q6: Viruses causing cancer, and causes of cancer 2nd Year Summer exams (2008/2009) Q1: Multiple-choice question of cross section of spinal cord with motor and sensory nerves Nigels lecture Q2: Pathogenesis of Atherosclerosis (not including fatty streak) and complications of heart disease/failure Q3: Stats - Kaplan Meier survival curve - kidney transplant survival Q4: SLE Autoimmune question - pathogenesis of autoimmunity, autoantibodies associated with it and treatments Q5: Multiple-choice question of Abdominal scan with questions about innervation and blood supply of gut Q6: Stats - Hardy Weinberg calculations for cystic fibrosis

SAMPLE QUESTIONS

1. ANTIBODIES Joan Duffy, who is 15 weeks pregnant, comes to her GP two days after she develops a flu-like illness. She has recently adopted a stray kitten. On examination, she is noted to have cervical lymphadenopathy and her GP is concerned that she has contracted toxoplasmosis. Serum antibody analysis shows a raised IgG antibody titre to Toxoplasma gondii but IgM antibodies are virtually undetectable. a. Describe the different isotypes of immunoglobulin and outline their structures (3 marks) b. Explain how an antigenic stimulus results in the production of immunoglobulins (2) c. Do Ms Duffys lab results indicate recent or remote exposure to Toxoplasma? Explain your answer (2) d. Outline the distribution of the cervical lymph nodes and the major anatomical structures that drain to them (3). (a) There are 5 isotypes IgM, IgG, IgA, IgD, IgE. Immunoglobulins consists of 4 polypeptide chains - 2 alpha chains - 2 heavy chains 5 types per group define class. The Fab portion is the antigen-binding site. The FC portion directs the biological activity. The variable region at the tips of the Y varies among different antibodies and determines the antigen specificity of the antibody. IgM pentamer IgG monomer 80% IgA mucosal dimer (b) B cells produce immunoglobulin that migrates to the cell surface to act as an antigen receptor. When stimulated by an antigen, the B cell differentiates into plasma cells that express large amounts of secreted IgM. Antibody production is increased by the stimulation of B cells by helper T cells. The secreted antibody circulates in the bloodstream and binds with the antigen that induced its synthesis. (c) Results indicate remote exposures. Antigen stimulation initially causes B cells to produce large amounts of IgM primary immune response. Some B cells undergo a class switch and differentiate into plasma cells expressing IgG secondary immune response. IgG with undetectable IgM indicates remote response. (d) The anterior cervical nodes are both superficial and deep and lie above and below the sternomastoid muscle. They drain the internal structures of the throat, posterior pharynx, tonsils and thyroid. The posterior cervical nodes extend in a line posterior to the sternomastoid but anterior to the trapezius, from the level of the mastoid process to the clavicle. They mainly drain the lungs.

2. OXYGEN Michael Jackson, a 57-year-old man has a cardio-respiratory arrest while watching a rugby match at Thomond Park. CPR is performed by St Johns Ambulance personnel, his heart beat is restored and his BP returns to normal (120/80). However, he had stopped breathing for at least 5 minutes before CPR was commenced. He is intubated and ventilated and transferred to the ITU at MWRH. a. Explain how the events described can lead to brainstem death (4 marks). b. Briefly explain why O2 is required for the body (3). c. Following his admission to hospital, how might the medical team reach a decision not to resuscitate Mr. Jackson in the event of another cardio-respiratory arrest? (3 marks)

(a) The brain has a high-energy requirement and cerebral anoxia for 3 4 minutes leads to irreversible damage. The brain can metabolise glucose anaerobically but this yields little energy while generating lactic acid, causing acidosis. Normally the brain is protected from harmful and highly reactive species of oxygen (e.g. superoxide, H2O2, hydroxyl radical) by protective enzymes (superoxide dismutase, peroxidase, catalase) and free radical scavenging agents (e.g. glutathione, Vit C). These enzymes are lost / reduced when the brain is anoxic. On reperfusion, the brain cannot eliminate the free radicals and toxic O2 derivatives, which continue to damage DNA, RNA, proteins and membranes. (b) O2 is required for the generation of ATP by oxidative phosphorylation. The step requiring O2 is the terminal step of the electron transport chain (ETC). In the ETC, NADH and FADH2 are reoxidised to NAD+ and FAD+ to allow the continuation of oxidation of fuels by the Krebs cycle. Without O2, ATP can only be generated by anaerobic glycolysis, generating little ATP and causing a build up of lactic acid. O2 is also required: - For the liver detoxification of drugs and other substances using the CYP450 system and NADPH - In the synthesis of bilirubin, steroid hormones, activated Vit D etc also using CYP450 - To generate heat of electron transport and oxidative phosphorylation are uncoupled. (c) A DNR decision is appropriate when: - CPR is likely to he futile - CPR is against the stated wishes of a mentally competent patient. Ideally the patients wishes in this regard should be formally documented. - Resuscitation is likely to be followed by a length and quality of life that would not be in the patients best interest - Advance directive - Involve patient and next of kin before emergency - When in doubt - resuscitate In Mr. Jacksons case, his next-of-kin might be asked their opinion of what Mr. Jackson would have wanted were he in a position to make a decision. All decisions made should be communicated and explained to his next of kin. 3. NTDs Susan Gallagher is a healthy 21-year-old woman accountancy student who is in a stable relationship. When in her teens, she suffered some epileptic seizures for which no cause could be found. She has been taking Sodium Valproate for about 6 years. She and her partner normally use barrier methods for contraception. One day she visits her GP because it is 8 weeks since her last period. A home pregnancy test on the previous day was strongly positive. Her major worry is that the baby will have a NTD because of the drug she is taking. (a) Briefly describe the nature of caudal NTDs and the forms they make take. Explain how they develop. (3 marks) (b) Susan asks whether stopping the sodium valproate is a good idea and whether it will reduce the chance of her baby having a NTD. What advice would you give and why? (2 marks) (c) Susan further asks if any tests can be done to see if her baby is normal. Explain what you would say to her. (3 marks) (d) Assuming that sodium valproate is the most effective anticonvulsant for Susan, what advice would you give her about planning future pregnancies? (2 marks) (a) Caudal NTDs develop during the rolling up of the flat neural plate to form the neural tube. If the edges of the caudal portion of the tube do not fuse, a defect known as spina bifida results. In spina bifida, the spinal cord is properly surrounded by the vertebral column. This ranges from a mild form, in which there is only a small defect in the neural arches and in which the skin is intact (occulta), through to conditions where the meninges with or without the spinal cord protrude from the spine, to a severe defect in which the spinal cord is split and completely exposed (myeloschesis). (b) Closure of the neural tube is complete by about 5 weeks of embryonic age. Stopping her drug at this stage (8 weeks) would not lessen the chance of a NTD. There is also a possibility of her seizures reoccurring if she were to stop her anticonvulsant. (c) There are several options: - an ultrasound is good in detecting structural defects in the vertebral column, as bone and cartilage readily reflect sound waves

an NTD results in alpha fetoprotein (AFP) leaking into the amniotic fluid in greater concentrations and this can be detected by sampling the maternal blood by a direct amniocentesis. (d) The dose of sodium valproate should be kept as low as possible and should be given in divided doses throughout the day because teratogenicity is dose-dependant and in the cases of sodium valproate, depends on peak levels. Susan should also take folic acid supplements and her serum folate levels should be monitored. -