82/56 Semester 2

THE UNIVERSITY OF SYDNEY PAPER 1 FACULTY OF MEDICINE UNIVERSITY OF SYDNEY MEDICAL PROGRAM YEAR 2

14 OCTOBER 2002

MED 2 SUMMATIVE

MEQ PAPER 1

ANSWER COPY

In general students will receive either a score of 2 or 0 for each of their answers. A student will score 2 marks if their answer fulfills the criteria of the MLC (minimum level of competence). A student will be given zero marks if their answer is incorrect or alternatively demonstrates significant misconceptions even if they have met the requirements of the MLC. If their answer is very close the MLC but doesn’t quite satisfy the criteria, you may give the student a score of 1. If a student has provided an answer that displays superior understanding of the question, exceeding the requirements of the MLC you may give the student a score of 3.

2

Competent answer (equivalent to the level of the minimum level of competence - MLC)

0 Unsatisfactory answer. The answer displays minimal or no understanding of the issue, or contains significant misconceptions.

3

Superior answer displaying a more comprehensive understanding than the MLC.

1 Very Close to the MLC. The answer does not meet the level of the competent answer, but does display some knowledge/understanding of the issue.

82/56 Semester 2

Case 1

Alan Peters is a 55 year old man who presents with sudden onset of severe abdominal and left shoulder tip pain. On examination his pulse rate is 120 per minute, systolic blood pressure 100 mmHg, with a postural drop (from lying to sitting) of 20 mmHg, his hands are cold and sweaty and there is board-like rigidity on abdominal examination. His initial WCC is *18.5 x 109/L (normal range (NR) 4.0-11.0 x 109/L). 1. List at least 3 known complications of peptic ulcer disease. Model Answer Peptic ulcer disease can lead to GIT bleeding via erosion of small vessels or larger arteries. Haemorrhage may occur from both gastric and duodenal ulcers. Peptic ulcers may be associated with scarring of surrounding tissues leading to stricture formation. This particularly occurs around the pylorus leading to pyloric obstruction Peptic ulcers may also erode through to the peritoneal surface. This is called perforation and may result in an acute abdomen pain + shock Answer should include: git bleeding obstruction perforation MLC 2/3 Curriculum reference: 7.07 Lec 6 Complications of peptic ulcer Suggested Time = 5 min Question 1 of 5 Cumulative Time = 5 min

82/56 Semester 2

Alan Peters is a 55 year old man who presents with sudden onset of severe abdominal and left shoulder tip pain. On examination his pulse rate is 120 per minute, systolic blood pressure 100 mmHg, with a postural drop of 20 mmHg, his hands are cold and sweaty and there is board-like rigidity on abdominal examination. His initial WCC is *18.5 x 109/L (NR 4.0-11.0 x 109/L). The initial imaging investigation obtained on Mr Peters was a PA Chest Radiograph, reproduced below. 2. a) Place an arrow on the abnormality in the image.

b) What is the correct term used to describe this abnormality? c) What is the most likely cause?

Model Answer

a) Either or both arrows placed as above. b) Free subphrenic gas OR free subdiaphragmatic gas OR free (intra)peritoneal gas. c) Perforated hollow intra-abdominal viscus OR perforated upper GIT (gastric or duodenal) ulcer. MLC Correct answers to ANY 2 out of 3 parts of the Question. Curriculum reference: 7.07 BCS2 Viewing of hollow organs Suggested Time = 5 min Question 2 of 5 Cumulative Time = 10 min

82/56 Semester 2

Alan Peters is a 55 year old man who presents with sudden onset of severe abdominal and left shoulder tip pain. On examination his pulse rate is 120 per minute, systolic blood pressure 100 mmHg, with a postural drop of 20 mmHg, his hands are cold and sweaty and there is board-like rigidity on abdominal examination. His initial WCC is *18.5 x 109/L (NR 4.0-11.0 x 109/L). 3. a) List 3 types of receptors on the basolateral membrane of gastric parietal cells whose stimulation results in an increase in acid secretion.

b) Give the cells of origin of the 3 agonists which stimulate these receptors. Model Answer a) Histamine type 2 receptors Gastrin receptors Acetylcholine (M3) receptors b) Histamine from enterochromaffin-like cells Gastrin from G cells Acetylcholine from vagal neuronal endings MLC 2/3 in each Curriculum reference: 7.07 LT4 Gastric secretion Suggested Time = 5 min Question 3 of 5 Cumulative Time = 15 min

82/56 Semester 2

Alan Peters is a 55 year old man who presents with sudden onset of severe abdominal and left shoulder tip pain. On examination his pulse rate is 120 per minute, systolic blood pressure 100 mmHg, with a postural drop of 20 mmHg, his hands are cold and sweaty and there is board-like rigidity on abdominal examination. His initial WCC is *18.5 x 109/L (NR 4.0-11.0 x 109/L).

4. a) With respect to the diagram above, identify the following structures: A. ___________________________ precise part at B. ___________________________ curvature at C. ___________________________ thickened part at D. ___________________________ organ and part at E. ___________________________

b) Name 2 structures not shown on the diagram that empty into E.

c) Name 2 structures that are related to (in contact with) E. Comprehensive answer a) A. oesophagus

B. fundus of stomach C. greater curvature of stomach D. pyloris (pyloric sphincter) E. second or descending part of duodenum

b). Bile duct, main pancreatic duct, accessory pancreatic duct (any 2 of these) c) Head of pancreas, gallbladder, liver, bile duct, transverse colon, right kidney, pancreatic ducts (any 2 of these), peritoneum, root of transverse mesocolon Satisfactory answer: Part 1: 3 of 5 Part 2: 1 accurate response Part 3: 1 of the suggested responses Reference: 7.06. Lecture, overview of gut structure and function, 7.06 BCS2, 7.08 BCS2 Suggested Time = 5 min Question 4 of 5 Cumulative Time = 20 min

82/56 Semester 2

Alan Peters is a 55 year old man who presents with sudden onset of severe abdominal and left shoulder tip pain. On examination his pulse rate is 120 per minute, systolic blood pressure 100 mmHg, with a postural drop of 20 mmHg, his hands are cold and sweaty and there is board-like rigidity on abdominal examination. His initial WCC is *18.5 x 109/L (NR 4.0-11.0 x 109/L). 5. a) Identify the pathophysiological sequence of events by which Helicobacter pylori infection

induces duodenal ulcer formation. b) Nominate at least one test which could be used to confirm H. pylori infection.

Model Answer a) Colonisation of gastric mucosa, usually the antrum, by Helicobacter pylori (Hp) Followed by epithelial injury and inflammation (gastritis) Ensuing destruction of D-cells (somatostatin); imbalance D and G-cells leads to gastrinaemia with increased acid production Hyperacidity stimulates metaplasia in duodenum with subsequent Hp colonisation and duodenitis Exposure of injured epithelium to chronic hyperacidity and Hp induced elevated pepsinogen levels causes further erosion leading to ulcer formation b) Mucosal biopsy at endoscopy, then cultured, or Serology, or Urea breath test MLC Essence of (a) plus one correct from (b) Reference : Lecture: 7.07 Peptic ulcer as an infection Suggested Time = 6 min Question 5 of 5 Cumulative Time = 26 min

END OF CASE 1

82/56 Semester 2

Case 2

Mr Clive Hokin is a 61 year old man who is approaching retirement. His wife is concerned he has lost interest in his home and work life and he expresses frustration at his inability to get things done. 1. Erikson’s psychosocial theory of development refers to the opposing tendencies of generativity and stagnation occurring during middle adulthood. Briefly describe at least 2 activities that are relevant to generativity. Answer Any two of the following points (it is not necessary to use the exact terms – the general idea will suffice): Procreativity - desire to have children. Productivity – desire to take care of things, maintain the world, make society better for one’s children, preserve things for future generations. Creativity – learning to accept the new, to continue to learn. Caring – nurturing, mentoring, taking care of others, developing ideas. Reference: 1.04 Lec 6 Middle adulthood Suggested Time = 5 min Question 1 of 5 Cumulative Time = 31 min

82/56 Semester 2

Mr Clive Hokin is a 61 year old man who is approaching retirement. His wife is concerned he has lost interest in his home and work life and he expresses frustration at his inability to get things done. His medical problems include hypertension, diabetes and obesity. On questioning you discover that he has been experiencing morning headache and increasing daytime somnolence. His wife has moved to another room because of his severe snoring. He drinks 80 g of alcohol per day and smokes 30 cigarettes per day. On examination he looks tired and pale. His blood pressure is 180/100, he has a thick “bull neck” and small oropharynx. His BMI is 35.

2. a) Identify the following structures: A. ____________________ Fold at B. ____________________ C. ____________________ Tissue at D. ____________________ E. ____________________ Part of pharynx F. ____________________ Part of pharynx G. ____________________ Part of pharynx H. ____________________

b) Name the cranial nerve that provides motor supply to C. ______________________________ Name the cranial nerve that provides sensory supply to G. ____________________________

Comprehensive answer a) A. Soft palate

B. Palatoglossal fold C. Tongue D. Palatine tonsils E. Epiglottis F. Nasopharynx G. Oropharynx H. Laryngopharynx

b) Cranial nerve 12 (hypoglossal nerve) provides motor supply to the tongue

Cranial nerve 9 (glossopharyngeal nerve) provides sensory supply to the oropharynx Either the number or the name of the cranial nerve is OK.

Satisfactory/adequate: Part 1 - Identification of 4 of 8 Part 2 - 50% correct for part 2. Reference: 3.04 BCS1, 6.04 BCS Cranial nerves Suggested Time = 5 min Question 2 of 5 Cumulative Time = 36 min

82/56 Semester 2

Mr Clive Hokin is a 61 year old man who is approaching retirement. His wife is concerned he has lost interest in his home and work life and he expresses frustration at his inability to get things done. His medical problems include hypertension, diabetes and obesity. On questioning you discover that he has been experiencing morning headache and increasing daytime somnolence. His wife has moved to another room because of his severe snoring. He drinks 80 g of alcohol per day and smokes 30 cigarettes per day. On examination he looks tired and pale. His blood pressure is 180/100, he has a thick “bull neck” and small oropharynx. His BMI is 35. 3. a) Nominate the 2 major sets of chemoreceptors that contribute to the control of respiration.

b) For each set of chemoreceptors briefly outline their roles and describe which stimuli they respond to.

Model Answer a) central and peripheral b) Peripheral - respond to decreases in blood PO2 (increases ventilation, high PO2 does not decrease ventilation), or to changes in blood PCO2 (high PCO2 increases ventilation, low PCO2 reduces ventilation - peripheral chemoreceptors responsible for around 20% of overall ventilatory response to changes in PCO2) or changes in blood pH (acidosis increases ventilation somewhat, alkalosis reduces ventilation a little). Central: mainly responds to changes in blood PCO2 via alterations in cerebrospinal fluid PCO2 (high PCO2 increases ventilation, low PCO2 reduces ventilation central chemoreceptors responsible for around 80% of overall ventilatory response to changes in PCO2 - tolerance occurs) MLC Must mention peripheral and central and which stimulus (or at least 2 of the peripheral stimuli) they respond to (underlined). At least 2 of the directions of change in ventilation must be correct (eg low O2 increases ventilation) Curriculum reference: 3.04 Lec 1 Control of respiration Suggested Time = 5 min Question 3 of 5 Cumulative Time = 41 min

82/56 Semester 2

Mr Clive Hokin is a 61 year old man who is approaching retirement. His wife is concerned he has lost interest in his home and work life and he expresses frustration at his inability to get things done. His medical problems include hypertension, diabetes and obesity. On questioning you discover that he has been experiencing morning headache and increasing daytime somnolence. His wife has moved to another room because of his severe snoring. He drinks 80 g of alcohol per day and smokes 30 cigarettes per day. On examination he looks tired and pale. His blood pressure is 180/100, he has a thick “bull neck” and small oropharynx. His BMI is 35. 4. a) What is the most likely diagnosis of this man’s sleepiness?

b) Nominate at least 3 other medical conditions which could be contributing to his sleepiness. Model Answer a) The most likely diagnosis is obstructive sleep apnoea. b) The other conditions, which are likely to contribute to his sleepiness, include: * His excessive alcohol intake with possible liver disease * Underlying CAL secondary to smoking contributing to the severity of nocturnal desaturation – Sleep Hypoventilation Syndrome *His weight. Again contributing to more severe nocturnal desaturation – Obesity Hypoventilation Syndrome. * Metabolic disturbances, in particular thyroid disease (seen with DM as well as obesity) as well as anaemia (the patient appears pale). MLC Obstructive Sleep Apnoea Excessive Alcohol Smoking Weight / obesity Curriculum reference: 3.04 LT1 chronic obstructive pulmonary disease; Lec 3 Pathophysiology of

sleep apnoea Suggested Time = 5 min Question 4 of 5 Cumulative Time = 46 min

82/56 Semester 2

Mr Clive Hokin is a 61 year old man who is approaching retirement. His wife is concerned he has lost interest in his home and work life and he expresses frustration at his inability to get things done. His medical problems include hypertension, diabetes and obesity. On questioning you discover that he has been experiencing morning headache and increasing daytime somnolence. His wife has moved to another room because of his severe snoring. He drinks 80 g of alcohol per day and smokes 30 cigarettes per day. On examination he looks tired and pale. His blood pressure is 180/100, he has a thick “bull neck” and small oropharynx. His BMI is 35. 5. What is the most useful diagnostic test for obstructive sleep apnoea and what specific information does this provide? Model Answer The most useful test would be a laboratory-attended polysomnograph. A home oximetry may be misleading particularly as there would be no information about the position of sleep and whether the patient achieved REM sleep. The later being of major importance in determining the possibility of respiratory or obesity-related hypoventilation. A full PSG would also allow you to detect possible arrhythmias or even see hypoxia related ischaemia, which would indicate further cardiac assessment to be warranted. Furthermore, the presence of central sleep apnoea could be determined and its severity appreciated. Oximetry offers no useful information in this condition. The presence of periodic limb movements can only be determined on PSG. They would increase the need to look for hypothyroidism and iron deficiency, and may in themselves contribute to sleep fragmentation. Unattended PSG is currently not recognised as being equivalent to the gold standard of laboratory PSG. Auto-titrating CPAP devices set in diagnostic mode have not been validated for the diagnosis of sleep disordered breathing and will not determine many measures of sleep quantity, quality or other non- respiratory measures such as ECG and leg movements. MLC Sleep Study:

Lab attended Identify that patient actually goes to sleep REM (sleep stages) Body position can be identified Cardiac arrhythmias or ischaemia can be identified Limb movements

Optional (comprehensive answer) compare with oximetry, CPAP, other devices. Curriculum reference: 3.04 - Sleeping on the job - Patient Data Suggested Time = 5 min Question 5 of 5 Cumulative Time = 51 min

END OF CASE 2

82/56 Semester 2

Case 3

Henry Xie is a 67 year old right handed man who was admitted to hospital with acute onset of weakness in his right upper and lower limbs and difficulty speaking. You suspect a stroke. Refer to the two supplied articles on cholesterol and stroke (in separate booklet) to answer the following questions. 1. Which of the following is each paper most concerned with - aetiology, frequency, diagnosis, prognosis, or intervention? Answer Study 1 (White et al): intervention Study 2 (Segal et al): aetiology NB Study 1 is a randomized controlled trial, and Study 2 a case-control study. MLC [Satisfactory for Q1 = Correct identification for both studies]. Suggested Time = 5 min Question 1 of 3 Cumulative Time = 56 min

82/56 Semester 2

Henry Xie is a 67 year old right handed man who was admitted to hospital with acute onset of weakness in his right upper and lower limbs and difficulty speaking. You suspect a stroke. Refer to the two supplied articles on cholesterol and stroke (in separate booklet) to answer the following questions. 2. Discuss at least 3 important aspects of validity with respect to each paper. Do not simply list the JAMA User’s Guide validity criteria. (Note you may use the same or different criteria for each paper – direct comparison of the papers is not required). Answer Study 1: White et al i) Was the assignment of patients to treatments randomized? Patients with a previous myocardial infarction or unstable angina with a cholesterol between 4-7mmol per litre were randomly assigned to receive pravastatin or placebo. Exact process not described. ii) Were all patients who entered the trial properly accounted for and attributed in its conclusions? 9014 patients were randomized, and followed-up for a mean of 6 years. The authors do not mention whether follow-up was similar for both groups, and whether there was any loss to follow-up. iii) Were patients analysed in the groups to which they were randomized? Analyses were performed on an intention to treat basis. This indicates that randomization was preserved. iv) Were patients, health workers, and study personnel ‘blind’ to treatment? Patients were randomly assigned in a double blind manner. Patients were given a placebo which ‘matched’ the pravastatin. All events reported as a stroke were reviewed by a Stroke Assessment Committee who were blinded with respect to study-group assignment. v) Were the groups similar at the start of the trial? Table 1 shows that the groups were similar, even with respect to cholesterol levels, except for a slightly higher level of triglycerides in the pravastatin group. vi) Aside from experimental observation, were the groups treated equally? Authors do not comment on this.

82/56 Semester 2

Study 2: Segal et al. i) Were there clearly identified comparison groups that were similar with respect to important determinants of outcome, other than the one of interest? The cases were hospital-based, and one control groups was population based while the other was from a primary care clinic. The groups were age and sex matched as shown in Table 2 (although they later mention that the practice control group were younger than the cases)and had similar exclusion criteria. The authors tried to minimize selection bias by not informing the controls that the research was on lipids until after enrollment. Recall bias is not an issue with regard to exposure as it did not depend on past history. ii) Were the outcomes and exposures measured in the same way in the groups being compared? Patients and investigators were not blinded to outcome. Measurement of exposure did not require blinding as it was a blood test. However it appears that cases had more blood tests, and cholesterol was measured with a different technique for the population based controls. iii) Was follow-up sufficiently long and complete? 70 patients were enrolled after exclusions and informed consent. Analyses were performed on 45 (64%) of these patients. 19 patients (27%) died prior to the follow up and 6 (9%) were lost to follow-up, so all cases were accounted for. No mention is made of follow-up of controls. iv) Is the temporal relationship correct? No, the exposure (cholesterol level) was measured after the outcome (intracerebral haemorrhage). v) Is there a dose response gradient? No, the authors just considered the cholesterol levels found in the lowest quintile of the control groups. MLC [Satisfactory for Q2 = Appropriate discussion of 3 of the above points for each paper using the JAMA criteria for validity. Two possible satisfactories]. Suggested Time = 20 min Question 2 of 3 Cumulative Time = 76 min

82/56 Semester 2

Henry Xie is a 67 year old right handed man who was admitted to hospital with acute onset of weakness in his right upper and lower limbs and difficulty speaking. You suspect a stroke. Refer to the two supplied articles on cholesterol and stroke (in separate booklet) to answer the following questions. 3. Refer to the paper by White et al entitled “Pravastatin therapy and the risk of Stroke” to answer the following questions: a) Using Table 2 on page 319, calculate the number needed to treat. (Use the figures from the first row – ‘Patients with stroke’, and show all working.) Answer: Number needed to treat (NNT) = 1/ absolute risk reduction (ARR) Absolute risk reduction = the difference in risk between control group (placebo) and the treated group (pravastatin). ARR = 204/4502 – 169/4512 = 0.00786 NNT = 1/0.00786 = 127.3 b) In the results section on page 323 the authors state that “treatment with pravastatin was associated with a reduction of 16% in the overall risk of stroke (95% confidence interval, -3 to 31%; P=0.10). Explain what this confidence interval means. Answer: There is a 95% chance that the true effect of pravastatin on stroke is between a 3% increase in stroke to a 31% decrease in stroke. MLC [Satisfactory for Q3 = Either a or b correct]. Overall criteria for satisfactory in EBM Med 2 Summative 2002: For satisfactory results in EBM summative, students are required to get 3 ‘satisfactories’ out of a possible 6. Students MUST gain at least one satisfactory from the SBA and one satisfactory from question 2 of the MEQ. There are a possible 2 satisfactories in the SBA and 4 in the MEQ. Suggested Time = 5 min Question 3 of 3 Cumulative Time = 81 min

END OF CASE 3

82/56 Semester 2

Case 4

Angela Clarke is a 31 year old woman who presents with double vision and a complaint of heaviness in the left arm and leg of subacute onset. Although she can walk, after about 200 metres she notices the left leg begins to drag. Examination shows there is incomplete abduction of the right eye when looking to the right and very mild weakness of the left arm and leg. The reflexes are brisker in the left limbs compared to the right and the left plantar response is extensor. 1. Describe possible anatomical explanations for these symptoms and signs. Model Answer A lesion in the right pons could affect the corticospinal fibres, which will cross to supply the left limbs. The right VI nerve nucleus or fibres associated with it could be affected on this side by the same lesion causing weakness of right abduction of the eye. (Less likely in this patient a space occupying lesion in the left hemisphere or upper brain stem could affect the left corticospinal tract and then the right VI nerve as a non lateralising sign of increased intra cranial pressure.) (Ref. Anatomy tutorials, Cranial nerve lectures.) MLC Left upper motor neurone signs (R cortical or brain stem) + R VI nerve lesion + one explanation eg: L UMN signs -> right sided pathology of cortex/brainstem ↓ Abduction -> right VI nerve palsy Explanations: single lesion in pons; two separate lesions affecting UMN + VI nerve signs Curriculum reference: 6.04 LT5 Ocular motor control; 6.07 LT2 Organisation of somatic motor systems Suggested Time = 6 min Question 1 of 6 Cumulative Time = 87 min

82/56 Semester 2

Angela Clarke is a 31 year old woman who presents with double vision and a complaint of heaviness in the left arm and leg of subacute onset. Although she can walk, after about 200 metres she notices the left leg begins to drag. Examination shows there is incomplete abduction of the right eye when looking to the right and very mild weakness of the left arm and leg. The reflexes are brisker in the left limbs compared to the right and the left plantar response is extensor. 2. Outline the general cranial nerve innervation of the extraocular muscles. In your answer, state the nerves involved and the muscles they innervate. Model Answer Oculomotor nerve (III) - innervates levator palpebral superior, superior rectus, inferior rectus, inferior oblique, medial rectus Abducent nerve (VI) - innervates the lateral rectus Trochlear nerve (IV) - innervates the superior oblique MLC Need at least 4 of underlined words including all 3 nerves. Curriculum reference: 6.04 LT5 Ocular motor control Suggested Time = 5 min Question 2 of 6 Cumulative Time = 92 min

82/56 Semester 2

Angela Clarke is a 31 year old woman who presents with double vision and a complaint of heaviness in the left arm and leg of subacute onset. Although she can walk, after about 200 metres she notices the left leg begins to drag. Examination shows there is incomplete abduction of the right eye when looking to the right and very mild weakness of the left arm and leg. The reflexes are brisker in the left limbs compared to the right and the left plantar response is extensor. These symptoms resolve completely after four weeks and Mrs Clarke is well for 18 months. She then presents again complaining that the vision from the right eye is misty, colours do not appear so bright through this eye, and movement of the eye is painful. 3. a) What is the most likely cause of the eye symptoms?

b) What abnormalities would you expect to find on ocular examination? Model Answer a) Optic neuritis. The classical features of reduced vision in one eye and pain on eye movement strongly suggest this diagnosis. (Ref. BCS visual testing) b) Abnormalities on testing of visual fields – most commonly a central or paracentral scotoma Delay in constriction of the right pupil compared to the left, when a bright light is alternately shone in each eye (swinging torch test) Fundoscopy is usually normal in the acute phase but if the lesion is anterior within the optic nerve then disc swelling or papillitis may be seen. MLC Optic neuritis and 2 abnormalities Curriculum reference: 6.05 BCS2 Visual pathways Suggested Time = 5 min Question 3 of 6 Cumulative Time = 97 min

82/56 Semester 2

Angela Clarke is a 31 year old woman who presents with double vision and a complaint of heaviness in the left arm and leg of subacute onset. Although she can walk, after about 200 metres she notices the left leg begins to drag. Examination shows there is incomplete abduction of the right eye when looking to the right and very mild weakness of the left arm and leg. The reflexes are brisker in the left limbs compared to the right and the left plantar response is extensor. These symptoms resolve completely after four weeks and Mrs Clarke is well for 18 months. She then presents again complaining that the vision from the right eye is misty, colours do not appear so bright through this eye, and movement of the eye is painful. This symptom also recovers after 2 months, except when tired or on a hot day, the vision again becomes indistinct in the right eye. One year later she develops mild weakness of the right leg and a burning sensation in the left leg. Her upper limbs are normal. Mrs Clarke also complains of urgency and frequency of micturition. Examination shows a loss of pain and hot/cold discrimination in the left leg. 4. a) What is the underlying diagnosis of Mrs Clarke? Justify your answer.

b) Where is the lesion responsible for the symptoms and signs in the lower limbs? State your reasons.

Answers a) The underlying diagnosis in Mrs Clarke is multiple sclerosis. There have been 3 different episodes affecting 3 different regions of the CNS with recovery of the first 2. Curriculum reference: 6.05 Lec5 Overview of Multiple Sclerosis: diagnosis b) The lesion is on the right side of the spinal cord probably in the thoracic region. Symptoms and signs in the arms would be expected if the lesion was in the cervical cord. The right spinal cord contains fibres traveling in the corticospinal tract to the right leg and ascending fibres in the spinothalamic tract traveling from the right leg, conveying pain and temperature sensation. Curriculum reference:6.01 LT3 Spinal cord structure and function longitudinal organisation; 6.06 LT5 Central pain pathways MLC a) MS b) Level + side Must have a) and b) for satisfactory. Suggested Time = 6 min Question 4 of 6 Cumulative Time = 103 min

82/56 Semester 2

Angela Clarke is a 31 year old woman who presents with double vision and a complaint of heaviness in the left arm and leg of subacute onset. Although she can walk, after about 200 metres she notices the left leg begins to drag. Examination shows there is incomplete abduction of the right eye when looking to the right and very mild weakness of the left arm and leg. The reflexes are brisker in the left limbs compared to the right and the left plantar response is extensor. These symptoms resolve completely after four weeks and Mrs Clarke is well for 18 months. She then presents again complaining that the vision from the right eye is misty, colours do not appear so bright through this eye, and movement of the eye is painful. This symptom also recovers after 2 months, except when tired or on a hot day, the vision again becomes indistinct in the right eye. One year later she develops mild weakness of the right leg and a burning sensation in the left leg. Her upper limbs are normal. Mrs Clarke also complains of urgency and frequency of micturition. Examination shows a loss of pain and hot/cold discrimination in the left leg. You have told Mrs Clarke you think she has multiple sclerosis. Mrs Clarke has a degree in biological sciences. She has read that multiple sclerosis is an ‘autoimmune disease.’ She asks you to explain what the term ‘autoimmune’ means. 5. a) Define ‘autoimmunity’.

b) Describe the possible target(s) of autoimmune attack in multiple sclerosis. Model Answer a) Autoimmunity is a breakdown in self-tolerance ie a breakdown of mechanisms that delete or render inactive lymphocytes with self-reactive antigen receptors. b) The targets of autoimmune attack are probably components of myelin, including myelin basic protein (MBP), proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG). MLC a) breakdown of self-tolerance b) components of myelin Including other details indicates above a satisfactory answer. Curriculum reference. 6.05 Learning topic. Autoimmunity of demyelination Suggested Time = 5 min Question 5 of 6 Cumulative Time = 108 min

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82/56 Semester 2

Angela Clarke is a 31 year old woman who has been diagnosed with multiple sclerosis. Mrs Clarke has a degree in biological sciences. She asks you for an explanation of what is happening in her brain. You sketch the diagram shown opposite for her. 6. Explain to her, following the numbers, the various cellular processes that are active in a lesion in her brain (refer to the diagram opposite). She will want to know:

a) What is the entire lesion within the dotted circle called? b) What is the primary pathogenic process and how does this affect nerve function? c) What structures are preserved in the lesion? d) What are these perivascular cells and what is their significance? e) What is this cell and what is its function? f) What is this cell and what is its function?

Model Answer a) The lesion is called a multiple sclerosis plaque. b) The axons in this plaque do not have their normal layer of myelin (demyelination), so nerve impulses will travel very slowly through them. c) The cell bodies and axons of neurons in the plaque are preserved, at least initially. d) Inflammatory cells, especially plasma cells, around small blood vessels suggest an immunological basis for the condition. e) Macrophages enter the plaque to mop up (phagocytose) the myelin that is removed from the axons. They may also actively strip myelin from the axons. f) Astrocytes form reactive scar tissue within the plaque. MLC 4 of the above points (must include point b) Curriculum reference: 6.05 Lecture Demyelination in the CNS Suggested Time = 6 min Question 6 of 6 Cumulative Time = 114 min

END OF CASE 4

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Case 5

Silvia Bianchi is a 28 year old woman with a past history of rheumatic fever, who is pregnant for the first time. During a routine review at 12 weeks gestation, she reports that she has had difficulty climbing stairs for the last week and gets “winded’ with minimal exertion. She notes some mild discomfort under the left breast when taking a deep breath or coughing. On examination her chest is clear to auscultation. 1. List at least 3 possible causes of dyspnoea in a pregnant woman. Model Answer Pulmonary embolism Lower respiratory tract infection Cardiac failure (valvular or cardiomyopathy) Dilutional anaemia Reduced venous return MLC 3 of the above Suggested Time = 5 min Question 1 of 4 Cumulative Time = 119 min

82/56 Semester 2

Silvia Bianchi is a 28 year old woman with a past history of rheumatic fever, who is pregnant for the first time. During a routine review at 12 weeks gestation, she reports that she has had difficulty climbing stairs for the last week and gets “winded’ with minimal exertion. She notes some mild discomfort under the left breast when taking a deep breath or coughing. On examination her chest is clear to auscultation. After further questioning by her GP, she admits to “tightness” behind the left knee for the last 2 weeks. Her left calf and thigh are marginally larger in diameter than the right, with no pitting oedema. Silvia is found to have an extensive left proximal deep vein thrombosis in the left leg and two mismatched perfusion defects in the left lung (a high probability scan for pulmonary embolism). 2. Regarding the venous system of the lower limb:

a) Name the two major superficial veins of the lower limb and their usual points of drainage into the deep system.

b) Describe at least one structure which acts to facilitate venous return in the deep venous system

and the mechanism by which it acts. Model Answer. a) The two major superficial veins of the lower limb are the long (great) and short (lesser) saphenous veins. The long saphenous vein joins the femoral vein in the femoral triangle and the short saphenous vein joins the popliteal vein in the popliteal fossa. b) Valves within the deep, superficial and communicating veins prevent blood flow within the veins from deep to superficial and proximal to distal. The muscles of the limb particularly the posterior leg (calf) muscles, which lie within the deep fascia and surround a deep venous plexus, by their contraction help pump blood towards the heart. Fractionated Marking. (MLC) 2 - A competent answer should . Name the two veins and indicate their points of drainage into the deep system. Name one of the facilitating structures and state the way in which it acts. 1 - An answer which falls short. Names only one of the veins and its point of drainage or omits the mechanism of action. 3 - A superior answer. Would include either details or additional relevant material. 0 - Unsatisfactory. Answers only one of the two parts or half of each of the two parts or includes additional material which is markedly incorrect or contradictory. Reference. 2.03 Lecture. Anatomy of the Knee, Leg, Ankle and Foot, Theme Session. Anatomy of the Knee, Leg and Foot, Curriculum reference: 4.05 LT Anatomy of venous system in leg Suggested Time = 5 min Question 2 of 4 Cumulative Time = 124 min

82/56 Semester 2

Silvia Bianchi is a 28 year old woman with a past history of rheumatic fever, who is pregnant for the first time. During a routine review at 12 weeks gestation, she reports that she has had difficulty climbing stairs for the last week and gets “winded’ with minimal exertion. She notes some mild discomfort under the left breast when taking a deep breath or coughing. On examination her chest is clear to auscultation. After further questioning by her GP, she admits to “tightness” behind the left knee for the last 2 weeks. Her left calf and thigh are marginally larger in diameter than the right, with no pitting oedema. Silvia is found to have an extensive left proximal deep vein thrombosis in the left leg and two mismatched perfusion defects in the left lung (a high probability scan for pulmonary embolism). 3. Describe the changes in pregnancy which increase the risk of thrombosis. MLC Mechanical obstruction to venous return by the uterus (L>R) Increased levels of procoagulant factors, particularly fibrinogen, vWF, II, VII, VIII and X Impaired fibrinolysis Reduced physical activity, bedrest Curriculum reference: 4.05 LT Effects of pregnancy on blood Suggested Time = 5 min Question 3 of 4 Cumulative Time = 129 min

82/56 Semester 2

Silvia Bianchi is a 28 year old woman with a past history of rheumatic fever, who is pregnant for the first time. During a routine review at 12 weeks gestation, she reports that she has had difficulty climbing stairs for the last week and gets “winded’ with minimal exertion. She notes some mild discomfort under the left breast when taking a deep breath or coughing. On examination her chest is clear to auscultation. After further questioning by her GP, she admits to “tightness” behind the left knee for the last 2 weeks. Her left calf and thigh are marginally larger in diameter than the right, with no pitting oedema. Silvia is found to have an extensive left proximal deep vein thrombosis in the left leg and two mismatched perfusion defects in the left lung (a high probability scan for pulmonary embolism). 4. a) Which proven therapies for venous thrombosis are safe during pregnancy?

b) Which commonly-used anticoagulant is considered unsafe in pregnancy? What problems are associated with this anticoagulant (nominate at least one problem)?

Model Answer a) Unfractionated heparin Low molecular weight heparin Optional - Compression stockings b) Warfarin + one effect - use in first 6 -9 weeks of pregnancy is associated with a specific embryopathy (characterised by nasal hypoplasia) - use in alter pregnancy can cause fetal bleeding leading to CNS damage - spontaneous abortion can also occur MLC any one of the above Suggested Time = 4 min Question 4 of 4 Cumulative Time = 133 min

END OF CASE 5

82/56 Semester 2

Case 6

Samuel Pantelis, a 10 year old boy, presents with increasing fatigue and drowsiness. A history of weight loss, polydipsia and polyuria is obtained. He is noted to have rapid breathing (24 per minute). On testing he is found to have a blood glucose of *25 mmol/L (NR 4-8 mmol/L). A diagnosis of Type 1 diabetes mellitus is considered. 1. What is the mechanism underlying the immunopathology in the pancreatic islets in Type 1 diabetes mellitus? Model Answer Recognition of self-antigen by T cells in the islets leads to recruitment of CD4 and CD8 T cells and macrophages to the islet and a cellular inflammatory response that destroys the islet B Cells. CD4 and CD8 T cells and local production of cytokines, including interferon-gamma (IFN-γ), lead to inflammation. The islet cell auto-antigens recognised include GAD (glutamic acid decarboxylase). The auto-immune basis is supported by associations with HLA-DR3 and DR4 and HLA-DQ2. MLC Two out of the following four (2/4): Cellular inflammation of islets Cytokine- interferon-gamma (IFN-γ) CD4 and CD8 T cells Autoantigens including GAD Curriculum reference: 7.01 lec 5 Autoimmunity in endocrine disease Suggested Time = 5 min Question 1 of 4 Cumulative Time = 138 min

82/56 Semester 2

Samuel Pantelis, a 10 year old boy, presents with increasing fatigue and drowsiness. A history of weight loss, polydipsia and polyuria is obtained. He is noted to have rapid breathing (24 per minute). On testing he is found to have a blood glucose of *25 mmol/L (NR 4-8 mmol/L). A diagnosis of Type 1 diabetes mellitus is considered. 2. Describe the main histological features and physiological functions of the endocrine pancreas. Model Answer The endocrine pancreas consists of about 1 million islets of Langerhans which consist of groups of cells and a network of fenestrated capillaries. Consist of beta cells (insulin) alpha cells (glucagon), D cells (somatostatin), minor islet cells (producing a range of gut hormones). MLC Islets of Langerhans; 2 cells types and 2 properly matched hormones Curriculum reference: 7.04 BCS2 Pancreas: normal & abnormal Suggested Time = 4 min Question 2 of 4 Cumulative Time = 142 min

82/56 Semester 2

Samuel Pantelis, a 10 year old boy, presents with increasing fatigue and drowsiness. A history of weight loss, polydipsia and polyuria is obtained. He is noted to have rapid breathing (24 per minute). On testing he is found to have a blood glucose of *25 mmol/L (NR 4-8 mmol/L). A diagnosis of Type 1 diabetes mellitus is considered. 3. a) List at least 3 important elements of insulin action on carbohydrate metabolism.

b) What is a likely metabolic explanation for his rapid breathing? Model Answer a) Insulin promotes the uptake and storage of glucose as glycogen and acts to suppress glycogen breakdown and gluconeogenesis. In muscle and fat cells, insulin receptor activation leads to the recruitment of GLUT-4 glucose transporters to the cell surface thereby facilitating glucose uptake from plasma and its intracellular trapping as glucose 6-phosphate. In hepatocytes and muscle cells, insulin activates glycogen synthase, the enzyme that regulates the control of glycogen synthesis from UDP-glucose. * insulin promotes glucose uptake into muscle and or fat * insulin activates glycogen synthesis OR glycogen synthase * suppresses glycogenolysis * suppresses gluconeogenesis b) He is likely to have ketoacidosis. Uncontrolled type 1 diabetes results in a metabolic disorder in which there is accelerated lipolysis and conversion of free fatty acids to ketone bodies.The attendant drop in plasma pH results in a compensatory tachypnea. MLC a) 3 of the points listed AND b) ketoacidosis, metabolic acidosis or respiratory compensation Curriculum Reference: 7.04: Learning Topic: Insulin in intermediary metabolism Suggested Time = 5 min Question 3 of 4 Cumulative Time = 147 min

82/56 Semester 2

Samuel Pantelis, a 10 year old boy, presents with increasing fatigue and drowsiness. A history of weight loss, polydipsia and polyuria is obtained. He is noted to have rapid breathing (24 per minute). On testing he is found to have a blood glucose of *25 mmol/L (NR 4-8 mmol/L). A diagnosis of Type 1 diabetes mellitus is considered. Samuel improves with fluids and the use of insulin. He requires long term insulin therapy. 4. Inadequate diabetic control over time can lead to microvascular diabetic complications. List 3 microvascular complications, each from a different organ system. Model Answer Retinopathy Nephropathy Peripheral neuropathy Autonomic neuropathy Necrobiosis lipoidica diabetocorum (NLD) (or equivalent description of the above) MLC 2 of the above, and must not have any confusion with macrovascular disease (stroke, IHD, PVD) Curriculum reference: 7.04 LT5 Chronic complications of diabetes Suggested Time = 3 min Question 4 of 4 Cumulative Time = 150 min

END OF CASE 6