Chem Path SBAs

Question 1

1. Arterial blood gas sampleA 67-year-old woman presents to accident and emergency after having a fall.She is diagnosed with a fractured neck of femur which is fixed with a hemiarthroplasty.She also suffers from metastatic breast cancer. Four days postoperatively,she develops shortness of breath with an increased respiratory rate of24 breaths per minute. The doctor on call takes an arterial blood gas samplewhich shows the following results:pH 7.48PaO2 15.4 kPa on 2 L of oxygenpCO2 2.6 kPaBase excess +1Saturations 99 per centWhat does the blood gas show?A Metabolic alkalosis with respiratory compensationB Metabolic alkalosisC Respiratory alkalosis with metabolic compensationD Respiratory alkalosisE None of the above

Answer 1

D Respiratory alkalosisThis lady has most likely suffered a pulmonary embolism manifestingas an acute onset of shortness of breath. Acid–base questions are bestapproached in three steps: first, decide if the pH shows an alkalosis or anacidosis. Next look at the PaCO2 and decide if it is high or low. Carbondioxide dissolves in water to form carbonic acid, a weak acid. Therefore,if the concentration of carbon dioxide is high, it will lower the pH. Youmust then decide if the PaCO2 is compounding or helping the patient’spH – in other words, is it worsening an acidotic patient or compensatingfor an alkalotic patient? Finally, look at the base excess. A greaterpositive base excess implies a higher concentration of bicarbonate, whichis a base. Unlike carbon dioxide, therefore, high levels of bicarbonatewill raise the pH. In this scenario, the pH is 7.48 meaning the patientis alkalotic with a low PaCO2, implying a respiratory cause. There is nocompensation as the base excess of +1 is within normal limits. Unlikerespiratory compensation, metabolic compensation takes several days.Below is a table of common causes of the different acid–base abnormalitieswith the likely carbon dioxide and base excess values.

Question 2

2. Paradoxical aciduriaA 19-year-old female student presents to the GP with low mood, lethargy andmuscle weakness. She is anxious that she is putting on weight and admits topurging after meals to keep her weight under control for several months. She hasa past history of depression and is taking citalopram. On examination, her bodymass index is 18, she is clinically dehydrated with signs of anaemia includingconjunctival pallor. She has bilateral parotidomegaly and the GP also noticeserosions of the incisors. He orders some blood tests which reveal the following:Hb 9.5White cells 7.8Platelets 345Na 143K 3.1Urea 8.5Creatinine 64Arterial pH 7.49Urinalysis is normal except for acidic urine. The cause of this patient’s acidicurine is:A Acute renal failureB Renal tubular acidosisC CitalopramD AnaemiaE Physiological

Answer 2

E PhysiologicalThis is a difficult question but the answer can be deduced with a basicknowledge of electrolyte physiology. This patient suffers from bulimianervosa as characterized by the use of characteristic purging after mealsto keep her weight under control. The main abnormalities in the investigationsreveal a hypokalaemia with arterial alkalosis and paradoxicalaciduria. The alkalosis is likely to be due to excessive purging leadingto a loss of hydrogen ions. The hypokalaemia is secondary to the metabolicalkalosis as potassium and hydrogen are transported across cellmembranes by the same transporter. The reduction of plasma hydrogenions leads to increased potassium uptake leading to hypokalaemia. Aspart of a normal homeostatic mechanism, potassium is exchanged for hydrogenions in the distal convoluted tubule of the nephron, resultingin an apparent paradoxical aciduria.

Question 3

3. HyponatraemiaA 55-year-old man with severe learning difficulties presents with shortness ofbreath on exertion, fever and a productive cough of rusty red sputum. On examination,there is increased bronchial breathing in the lower right zone with inspiratorycrackles. The patient is clinically euvolaemic, and urine dipstick is normal.A chest X-ray demonstrates right lower zone consolidation with the presence ofair bronchograms. He is on carbemezepine for epilepsy and risperidone. Bloodtests reveal the following:Hb 13.4White cell count 12.8C reactive protein 23Na 123K 4.7Urea 6Creatinine 62What is the most likely cause of hyponatraemia?A PneumoniaB CarbamezepineC RisperidoneD Syndrome of inappropriate antidiuretic hormone (SIADH)E Cerebral salt wasting syndrome

Answer 3

B CarbamezepineThis patient’s hyponatraemia is most likely secondary toCarbamezepine therapy (B), a well documented side effect of this antiepilepticmedication. Carbamezepine stimulates the production of vasopressin,the mechanism of action of which will be discussed shortly.It is also one of the ‘terrible 3 Cs’ which cause aplastic anaemia, theother two being carbimazoleand chloramphenicol. Any patient withsigns of infection or bleeding must be taken very seriously as fulminantsepsis may ensue without prompt treatment. This patient, however,has mounted a white cell response with a normal platelet counttherefore making aplastic anaemia unlikely.Pneumonia (A) does not normally cause a sodium abnormality on itsown. Less commonly, Legionnaire’s disease caused by the bacteriumLegionella pneumophilia can have extrapulmonary features includinghyponatraemia, deranged liver function tests and lymphopenia. This isunlikely to be the case as this organism often colonizes water tanks inplaces with air conditioning and has a prodromal phase of dry coughwith flu-like symptoms. The alternative indirect pulmonary cause ofhyponatraemia is lung cancer producing a SIADH; the tumour predisposesthe patient to pneumonia by obstructing the normal ciliary clearance of the bronchi. It is unlikely in this patient given the lack ofsmoking history or cachexia.

Question 4

HypercalcaemiaA patient with end stage renal failure presents with depression. He is on haemodialysisthree times a week but feels it is not working anymore and is getting moretired lately. He says he has lost his appetite and consequently feels rather constipatedtoo. He feels his mind is deteriorating and there is little worth in attendingdialysis anymore. His doctor wants to exclude a reversible cause of his depressionand orders some blood tests. The doctor finds the patient has a raised correctedcalcium, normal phosphate levels and high parathyroid hormone levels. What is thediagnosis?A Primary hyperparathyroidismB Secondary hyperparathyroidismC Tertiary hyperparathyroidismD PseudohypoparathyroidismE Pseudopseudohypoparathyroidism

Answer 4

C Tertiary hyperparathyroidismThis patient has tertiary hyperparathyroidism (C) given the presence ofelevated calcium levels with high parathyroid levels in the presence ofchronic renal failure. Plasma calcium levels are controlled via parathyroidhormone (PTH) which is produced in the parathyroid glands situatedwithin the thyroid gland. Reduced ionized calcium concentrationis detected by the parathyroid glands leading to a release of PTH whichcirculates in the blood stream. PTH increases calcium resorption from the kidneys whilst increasing phosphate excretion. PTH also stimulates1-alpha hydroxylation of 25-vitamin D to make 1,25-vitamin D. Finally,PTH increases bone resorption of calcium via osteoclast activation.The sum effects of increased PTH levels are to increase plasma calciumconcentration and to reduce phosphate concentration. PTH has an indirect,but very important, mechanism via 1,25-vitamin D which acts toincrease gut absorption of calcium.Tertiary hyperparathyroidism (C) is seen in the setting of chronic renalfailure and chronic secondary hyperparathyroidism leads to hyperplasticor adenomatous change in the parathyroid glands resultingin autonomousPTH secretion. The causes of calcium homeostasis dysregulationare multifactorial including tubular dysfunction leadingto calciumleak, inability to excrete phosphate leading to increased PTH levelsand parenchymal loss resulting in lower activated vitamin D levels.

Question 5

Vitamin deficiency testsA 59-year-old man presents with a fall and haematemesis after a heavy nightdrinking at the local pub. This is his third admission in a month with alcoholrelatedproblems. He has stopped vomiting, and on examination he is haemodynamicallystable. He has digital clubbing, spider naevi and gynaecomastia. He isadmitted for neurological observations overnight as he hit his head. The doctorsnotice the patient suffers from complex ophthalmoplegia, confusion and ataxia.Given his neurological symptoms which test would confirm the associated vitamindeficiency?A Red cell folateB Red blood cell transketolaseC Red blood cell glutathione reductaseD Red blood cell aspartate aminotransferase activityE Carbohydrate deficient transferrin

Answer 5

B Red blood cell transketolaseThis patient suffers from chronic alcohol abuse with signs of chronicliver disease. He also exhibits the classical triad of Wernicke’s encephalopathycaused by a thiamine (vitamin B1) deficiency. The test for thisis measuring red blood cell transketolase activity (B). Red cell transketolaseis a thiamine pyrophosphate requiring enzyme which catalyzesreactions in the pentose phosphate pathway essential for regeneratingNADPH in erythrocytes. The test measures enzyme activity by addingthiamine pyrophosphate to a sample of haemolyzed red blood cellsand measuring the effluent substances. By calculating the amount ofproduct made and substrates consumed, one is able to calculate theincrease of enzyme activity after thiamine addition. A marked increasein activity implies a thiamine deficiency as the other substrate (ribose5 phosphate) is supplied in excess. Thiamine deficiency has a numberof clinical sequelae including Wernicke’s encephalopathy, a reversibleneurological manifestation characterized pathologically by haemorrhagein the mammillary bodies. If left untreated, this may progress toKorsakoff’s syndrome, an irreversible neurological disease characterizedby severe memory loss, confabulation, lack of insight and apathy.Thiamine deficiency can also lead to wet beriberi syndrome leading toa high output cardiac failure.

Question 6

HyperkalaemiaA 75-year-old man presents with acute onset abdominal pain. The patienthas not passed stools for 3 days and looks unwell. His past medical historyincludes bowel cancer which was treated with an abdominoperineal resectionand chemotherapy 6 years ago. On examination, there is a large parastomalmass which is tender and irreducible. An arterial blood gas shows metabolicacidosis with a rasied lactate. The on-call doctor immediately starts normalsaline fluids and prepares the patient for theatre. A strangulated hernia is diagnosedby the registrar and an emergency laparotomy is performed to resect theischaemic bowel. One day postoperatively the patient has the following bloodresults:Hb 13.2WCC 10.9Platelets 234Na 145K 6.3pH 7.38Urea and creatinine normalWhat is the most likely cause of hyperkalaemia?A Acute kidney injuryB Tissue injuryC Resolving metabolic acidosisD Adrenal failure from metastasesE Overhydration from intravenous fluids

Answer 6

B Tissue injuryThe most likely cause of this patient’s hyperkalaemia is secondary totissue injury. Potassium is the principle intracellular cation whereassodium is the principle extracellular cation. Na–K exchange pumpsrequire a continuous supply of adenosine triphosphate (ATP) to supplythe energy required to maintain the transcellular gradient. In iscliaemic conditions, where oxygen supply is limited, ATP production fails tomeet demand via aerobic respiration alone. Therefore ATP is also generatedvia anaerobic respiration. This can only occur for a limited periodas the anaerobic pathway is both less efficient and produces lactic acid,thereby reducing the local pH and reducing the efficiency of enzymaticactivity. This patient has had a significant amount of infarcted bowelremoved with a raised lactate implying anaerobic metabolism has bothoccurred and ultimately failed leading to cell necrosis. The cells are thenunable to maintain the Na–K transporter activity leading to potassiumrelease in the blood stream. Furthermore, surgery itself causing directcell damage increases the intracellular potassium leak into the plasma.

Question 7

HypernatraemiaA 54 year old with a background of hypertension, presents to the GP with a2-week history of diarrhoea. He has been travelling in South East Asia recentlyand developed symptoms of diarrhoea 3 weeks ago. He went to the local doctorwhilst in China who prescribed tetracycline, but his symptoms have persisted andonly improved slightly. His past medical history includes an undisplaced parietalskull fracture he sustained when he was 10. He takes no other medications. TheGP orders blood tests which show the following:Na 148K 4.8Urea 13Creatinine 112What is the most likely cause of his hypernatraemia?A Conn’s syndromeB Nephrogenic diabetes insipidusC Cranial diabetes insipidusD TetracyclineE Dehydration

Answer 7

E DehydrationThe most likely cause of hypernatraemia in this man is dehydration (E).Gastroenteritis with diarrhoea for 3 weeks causes a high rate of freewater loss resulting in increased concentration of sodium in the extracellularcompartment. Sodium and intravascular volume are closelylinked and controlled by the renin angiotensin system and antidiuretichormone. A reduction in renal blood flow through loss of intravascularvolume results in increased renin secretion from the juxtaglomerularapparatus in the kidneys. Renin converts angiotensinogen to angiotensinI which in turn is converted to angiotensin II by angiotensinconverting enzyme (which is constitutively expressed in the lungs).Angiotensin II increases the release of aldosterone from the zona glomerulosain the adrenal cortex which acts to increase sodium retention.Retained sodium increases plasma osmolality which stimulates antidiuretichormone (ADH) release from the posterior pituitary. ADH acts toincrease free water retention, the net result being an increased intravascularvolume with a normal osmolality.

Question 8

Water deprivation testA 42-year-old woman with persistent polyuria and polydipsia is admitted for awater deprivation test. At the beginning of the test her weight, urine volume andosmolality and serum osmolality are measured and hourly thereafter for 8 hours.After 8 hours, she is given intramuscular desmopressin but drinks 3 L of waterbefore going to bed. Her blood is taken again the next morning (16 hours afterbeginning the test) and the results are as follows:Start 8 hours 16 hoursWeight 70 kg 67.8 kg 66.8 kgUrine volume (total) 0 mL 2200 mL 4000 mLUrine osmolality 278 mosmol/kg 872 mosmol/kg 980 mosmol/kgWhat is the most likely diagnosis?A Nephrogenic diabetes insipidusB Craniogenic diabetes insipidusC Psychogenic polydipsiaD Invalid testE Normal

Answer 8

C Psychogenic polydipsiaThis patient is most likely suffering from psychogenic polydipsia, anuncommon condition where excessive water drinking occurs without thephysiological stimulus to drink. It was classically described in patientswith schizophrenia but also occurs in children. Chronic psychogenicpolydipsia can result in mineral washout of the renal interstitium resultingin a physiological inability to concentrate urine, in other words aform of nephrogenic diabetes insipidus.

Question 9

Acute abdominal painA 24-year-old previously fit and well woman presents with sudden onsetabdominal pain the night after a party where she drank five units of alcohol. Shecomplains of central abdominal pain, with nausea and vomiting. She also findsit difficult to control her bladder. On examination, she is tachycardic, hypertensiveand is beginning to become confused. On looking back at her previousadmissions, the doctor notices she has had similar episodes after drinking. Thiswas also true for when she started the oral contraceptive pill and when she hadtuberculosis which was treated with standard antibiotic treatments. She is alsoseeing a neurologist for peripheral neuropathy of unknown cause. The admittingdoctor, an Imperial college graduate, suggests the possibility of acute intermittentporphyria. What enzyme deficiency is responsible for this disease?A Porphobilinogen deaminaseB Uroporphyrinogen synthaseC Coproporphyrinogen oxidaseD Protoporphyrinogen oxidaseE Uroporphyrinogen decarboxylase

Answer 9

A Porphobilinogen deaminasePBG deaminase deficiency (A) causes acute intermittent porphyria,which this patient suffers from. The porphyrias are a group of sevendisorders caused by enzyme activity reduction in the haem biosyntheticpathway. Haem is manufactured in both the liver and bone marrowwhere branched chain amino acids together with succinyl CoA andglycine are needed. The first step involves 5 aminolevulinic acid (ALA)synthesis by ALA synthase. This is the rate limiting step which is undernegative feedback from haem itself.

Question 10

Exacerbating factors for goutA patient presents with an acutely painful, inflamed elbow. He has decreased rangeof movement passively and actively and the joint is tender, erythematous and warm.His past medical history includes hypertension, chronic lower back pain for whichhe takes aspirin, lymphoma for which he has just completed a course of chemotherapyand psoriasis which is well controlled. He is also a heavy drinker. A joint aspirateshows weakly negative birefringent crystals confirming the diagnosis of acutegout. Which factor in this patient is the least likely to contribute to this attack?A BendroflumethiazideB ChemotherapyC AlcoholD PsoriasisE Aspirin

Answer 10

D PsoriasisAlthough all of these factors can contribute to hyperuricaeamia, wellcontrolled psoriasis (D) in this patient is unlikely to contribute to thisattack of gout. Gout may be acute or chronic and is caused by hyperuricaemia.Hyperuricaemia is caused either by increased urate productionor decreased urate excretion.Uric acid is a product of purine metabolism and is produced in threemain ways – metabolism of endogenous purines, exogenous dietarynucleic acid and de novo production. De novo production involvesmetabolizing purines to eventually produce hypoxanthine and xanthine.The rate limiting enzyme in this pathway is called phosphoribosyl pyrophosphate aminotransferase (PAT) which is under negative feedbackby guanine and adenlyl monophosphate. The metabolism of exogenousand endogenous purines, however, is the predominant pathway foruric acid production. The serum concentration of urate is dependenton sex, temperature and pH. A patient with acute gout does not necessarilyhave an increased urate concentration, therefore making serumurate levels an inaccurate method of diagnosis. The diagnosis of acutegout, which most commonly affects the first metatarsophalangeal joint(‘podagra’) is best made by observing weakly negatively birefringentcrystals in an aspirate of the affected joint. This test is performed withpolarized light – urate crystals are rhomboid and illuminate weaklywhen polarized light is shone perpendicular to the orientation of thecrystal (hence negative birefringence). This is in contrast with pseudogoutwhich has positively birefringent, spindly crystals – theseilluminate best when the polarized light is aligned with the crystals.X-ray of the affected joint shows soft tissue inflammation early on,but as the disease progresses, well defined ‘punched out’ lesions in thejuxta-articular bone appear with a late loss of joint space. There is nosclerotic reaction. Treatment is with a non-steroidal anti-iflammatory(e.g. diclofenac) in the acute phase or colchicine.

Question 11

Anion gapA patient has the following blood results; calculate the anion gap:Na 143 mmol/LK 4 mmol/LCl 107 mmol/LHCO3 25 mmol/LPO4 1 mmol/LGlucose 8 mmol/LUrea 7 mmol/LA 14 mmol/LB 15 mmol/LC 16 mmol/LD 17 mmol/LE Not enough information

Answer 11

A 14 mmol/LThe anion gap is calculated using the following equation:Anion gap = [Na+] + [K+] − [HCO3] − [Cl−]It is a method of assessing the contribution of unmeasured anions inmetabolic acidosis. The normal range varies between laboratories butthe upper limit is usually between 10 and 18 mmol/L. It is helpful toestimate the unmeasured anions such as phosphate, ketones and lactatewhich are difficult to measure normally.

Question 12

Estimated plasma osmolarityA patient has the following blood results:Na 143 mmol/LK 4 mmol/LCl 107 mmol/LHCO3 25 mmol/LPO4 1 mmol/LGlucose 8 mmol/LUrea 7 mmol/LWhat is the estimated plasma osmolarity?A 309B 279C 426D 294E Not enough information

Answer 12

A 309Estimated plasma osmolarity is calculated using the following equation:Estimated plasma osmolarity = {[Na+] + [K+]} × 2 + [glucose] + [urea]The estimation of osmolarity is an approximation of the laboratoryplasma osmolality which is always higher. The difference betweenosmolarity and osmolality is the quantity of solvent one is referringto – the former describes the osmoles of solute in 1 kg, whereas the latterdescribes the same solute in 1 L of solvent. Sodium and potassiumare the main plasma cations, they are doubled to take into account theequal concentration of total anions present to maintain electrical neutrality.Glucose and urea are the other main osmolites even though ureahas very little osmotic effect in the plasma. It is a very small moleculethat can pass easily through cell membranes without affecting osmoticpressure.

Question 13

Biochemical abnormalities in chronic renal failureA 67-year–old man with chronic renal failure presents with fatigue. He has been onhaemodialysis three times per week for a decade. His past medical history includesdiabetes mellitus, hypertension and gout. He has been increasingly tired the last fewweeks although he cannot explain why. He has been attending his dialysis appointmentsand is compliant with his medications. The GP takes some bloods to investigate.Which of the following is NOT a common association with chronic renal failure?A AcidosisB AnaemiaC HyperkalaemiaD HypocalcaemiaE Hypophosphataemia

Answer 13

E HypophosphataemiaPatients with chronic renal failure normally suffer from hyperphosphataemia,not hypophosphataemia (E). This is due to renal impairmentof calcium metabolism which is under the control of parathyroidhormone (PTH) and vitamin D. In the evolving stages of chronic renalfailure, a secondary hyperparathyroidism exists to compensate forthe inabilityof the kidney to retain calcium and excrete phosphate.Therefore hypocalcaemia(D) is associated with chronic renal failure.This stimulates a physiological secretion of PTH by the parathyroidglands in an attempt to retain calcium. PTH is also responsible forexcreting phosphate in the kidney, which is impaired due to the failure.Hyperphosphataemia also increases PTH levels as part of a negativefeedback loop designed to maintain its homeostasis. Patients withchronic renal failure usually take phosphate binders (e.g. Sevelamer)which act to reduce phosphate absorption. This reduces PTH productionwhich also reduces bone resorption thus improving renal osteodystrophy,a complex metabolic bone pathology associated with chronic renalfailure. It is also important to reduce phosphate concentration to reduceectopic calcification – if this precipitatesin the tubules, this may reducewhat little function there is left.

Question 14

Thyroid function testsA 45-year-old woman presents feeling tired all of the time. She has been investigatedfor anaemia which reveals macrocytosis. She denies drinking excessively.She has recently moved house and the GP notices she has a croaky voice, peachesand cream complexion and a slowed reaction to his questions. He examinesher and elicits slow relaxing ankle reflexes. He suspects hypothyroidism andorders some thyroid function tests.Which of the following results are consistentwith primary hypothyroidism?A Low TSH, raised free T4 and T3B Low or normal TSH with low free T4 and T3C Raised TSH with normal free T4 and T3D Normal or raised TSH with raised T4 and T3E None of the above

Answer 14

E None of the aboveThyroid function tests are relatively easy to interpret with a basicunderstanding of the hypothalamic–pituitary–thyroid axis of thyroidhormone control. The pituitary produces TSH (thyroid stimulatinghormone) which is released from the anterior pituitary. It is under thecontrol of the hypothalamus which releases thyroid releasing hormone(TRH) which signals to anterior pituitary cells to release TSH. TSHtravelsin the bloodstream and acts on thyrocytes in the thyroid glandto stimulate production of T4 and T3 hormone. Specifically TSH controlsthe rate of iodide uptake required for thyroid hormone production,thyroid peroxidase activity, iodotyrosine reuptake into the thyrocytefrom colloid and iodotyrosine cleavage to form mature hormone. T4 isthe main circulatory hormone produced in about a 10:1 ratio comparedwith T3. However, free T3 has greater efficacy; in fact circulating T4 isconverted into T3 within cells which then binds to its hormone receptor.TSH release is under negative feedback control of T4. In primaryhypothyroidism,the thyroid does not have the ability to produce sufficientT4 or T3 to inhibit further TSH release. Therefore the biochemicalabnormality found in primary hypothyroidism is a raised TSH with lowT4 and T3, which is not one of the answer options (E).

Question 15

Biochemical abnormalities of metabolic bone diseaseAn 86-year-old woman presents to accident and emergency after a fall. She is afrequent faller but was unable to weight bear after the most recent incident. Shehas a history of rheumatoid arthritis which is controlled with low dose prednisolone.On examination her right leg is clinically shortened and externally rotatedand a pelvic X-ray confirms the presence of a fractured neck of femur. The patient’ship is fixed the next day. Her day one postoperative bloods show the following:Corrected calcium normalPhosphate normalAlkaline phosphatase raisedParathyroid hormone level normalVitamin D level lowWhat is the most likely diagnosis?A NormalB OsteoporosisC Paget’s diseaseD OsteomalaciaE Malignancy

Answer 15

B OsteoporosisOsteoporosis (B) is a common disease which affects women more thanmen. It is pathologically associated with a reduction in bone densitybut normal mineralization of bone. There are usually no biochemicalabnormalities and therefore all of the parameters measured here shouldbe normal. Given the nature of the fracture, the raised alkaline phosphataseis likely to be due to the fracture where osteoblast and osteoclastactivation for remodelling and bone healing is required for boneunion. Note osteoblasts produce alkaline phosphatase, not osteoclasts.The activation of the two is usually simultaneous, therefore any bone remodelling will lead to a rise in alkaline phosphatase concentration.An important exception is in myeloma where bone lysis occurs with norise in alkalaline phosphatase because osteoclasts are directly activatedwithout osteoblast activity. Recently the National Institute of ClinicalExcellence (NICE) have published guidelines regarding osteoporosis andits management. The risk factors of osteoporosis include:1 Genetic factors: woman, age, Caucasion/Asian, family history2 Nutritional factors: excessive alcohol and caffeine, low body weight3 Life style factors: inactivity, smoking4 Hormonal factors: nulliparous women, late menarche/early menopause,oophorectomy, post menopausal women, amenorrhoea5 Iatrogenic factors: thyroxine replacement, steroids

Question 16

Inherited metabolic disordersA 42-year-old woman presents to maternity in labour. It is her first child andshe delivers a baby boy at 42 weeks gestation. During the neonatal period, thechild develops feeding difficulty with hypotonia and jaundice. On examinationthere is a conjugated hyperbilirubinaemia. The mother thinks this has startedshortly after she has started feeding the child with milk. After a few months,the child develops cataracts. On testing the urine, there is positive Fehling’s andBenedict’s reagent tests with a negative glucose oxidase strip test. The milk iseliminated from the child’s diet and immediately some of the symptoms improve.What is the diagnosis?A Fructose intoleranceB GalactosaemiaC Galactokinase deficiencyD Urea cycle disorderE Tyrosinaemia

Answer 16

B GalactosaemiaThis neonate, born with cataracts, poor feeding, lethargy, conjugatedhyperbilirubinaemia with hepatomegaly and reducing sugars in theurine after starting milk, is likely to have galactosaemia (B). This is arare autosomal recessive inherited condition most commonly due to amutation in the galactose-1-phosphate uridyltransferase gene on chromosome9p13. It results in excessive galactose concentrations whenmilk, which contains glucose and galactose, is introduced into thebaby’s diet.

Question 17

Neonatal jaundiceA 2-week-old neonate born at term with no gestational complications developsuncongutated jaundice. This was following a difficult birth where instrumentationwas required after excessive delay in the second stage of labour. On examination,the neonate looks well in a normal flexed position with visible jaundice mostnoticeable in the soft palate. There are no abnormal facies but there is a visiblelarge caput succedaneum with bruising. Urine dipstick is normal with no markersof infection present in the blood. What is the most likely cause of the jaundice?A Urinary tract infectionB BruisingC HaemolysisD Crigler–Najjar syndromeE Gilbert’s disease

Answer 17

B BruisingThis child, with a large amount of bruising (B), most probably developedunconjugated jaundice from the excess breakdown products of erythrocytes.The difficult labour requiring instrumentation has led to a largecollection of bruising in the scalp which is broken down and leads tounconjugated jaundice. Neonates are susceptible to jaundice for manydifferent reasons – reduced erythrocyte half life with increased haemoglobinlevels, reduced transport in the liver (reduced ligandin is responsiblefor this) and increased enterohepatic circulation. Investigation ofthis is to rule out other causes including urinary tract infection, otherhaemolytic anaemias and congenital hypothyroidism which is normallytested for by the heel prick Guthrie test. Treatment is usually via phototherapywhich uses light at 450 nm wavelength to solubilize (NOTconjugate) the excess bilirubin for excretion through the kidneys. Thisprevents passage of bilirubin through the immature blood–brain barrierwhich can then deposit into the basal ganglia causing kernicterus.Another method of treatment includes exchange transfusion.

Question 18

Vitamin D deficiencyA 54-year-old man with a past history of alcohol abuse, recurrent severe epigastricpain with flatulence and steatorrhoea presents after a fall whilst out drinkingwith his friends. He had fallen onto his hip, has severe pain and inability toweight bear. On examination, his right lower limb is shortened and externallyrotated. His liver function tests were normal apart from a raised alkaline phosphatase.A fractured neck of femur is diagnosed and is fixed that night. As partof a routine follow up, the fracture liaison nurse suspects vitamin D deficiencyand orders a full set of vitamin D levels. What set of results would you expect inthis man given his history?A Low 25-hydroxycholecalciferol, low 1,25-dihydroxycholecalciferol,low parathyroid hormoneB Low 25-hydroxycholecalciferol, high 1,25-dihydroxycholecalciferol, high parathyroid hormoneC High 25-hydroxycholecalciferol, low 1,25-dihydroxycholecalciferol,high parathyroid hormoneD High 25-hydroxycholecalciferol, high 1,25-dihydroxycholecalciferol, highparathyroid hormoneE High 25-hydroxycholecalciferol, low 1,25-dihydroxycholecalciferol,low parathyroid hormone

Answer 18

B Low 25-hydroxycholecalciferol, high 1,25-dihydroxycholecalciferol, highparathyroid hormoneThis man is highly likely to have osteomalacia given the history ofchronic alcohol abuse and episodes consistent with chronic pancreatitis.This is significant because the pancreas is responsible for emulsificationand digestion of fats which facilitate fat soluble vitamin absorptionincluding vitamins A, D, E and K. The reduced vitamin D absorptionhas led to osteomalacia, the pathological syndrome caused by vitaminD deficiency after epiphyseal closure. If vitamin D deficiency occurredbefore epiphyseal closure, the patient would suffer from rickets.

Question 19

Raised alkaline phosphataseWhich of the following is not a cause of raised alkaline phosphatase levels?A PregnancyB Paget’sC Congestive heart failureD Obstructive jaundiceE Myeloma

Answer 19

E MyelomaAlkaline phosphatase (ALP) is an enzyme responsible for removingphosphate groups from various molecules. It is produced in the liver,bile duct, kidney, bone and placenta. It is commonly requested aspart of the liver function test panel and is used diagnostically in theapproach to various conditions.Of these answers, only myeloma does not classically cause a raisedALP. ALP is caused by osteoblast activation whereas in myeloma thereis direct osteoclast activation through the release of various cytokines.

Question 20

Nutritional deficiencyA 44-year-old African man is seen by a volunteer doctor in his village with skinchanges around the neck. There are erythematous and pigmented areas around theneck in a necklace-like distribution. His family is also complaining of him becomingmore forgetful and unable to perform normal daily tasks. This is made particularlydistressing given his increase in bowel movements, although he cannot rememberhow many times he goes. He and his family, like many of the villagers, eat almostexclusively maize, and the doctor has treated several cases of kwashiorkor in thelocal area. What is the nutritional deficiency most likely to explain his symptoms?A TocopherolB RiboflavinC RetinolD Vitamin B3E Ascorbate

Answer 20

D Vitamin B3This man with poor diet, dermatitis, dementia and diarrhoea most likelyhas a niacin deficiency leading to pellagra. The other name for niacin isvitamin B3 (D).The rash he describes is also known as Casal’s necklace–a distinctive erythematous, pigmented rash in the necklace distributionnamed after Gaspar Casal, a Spanish physician practising in the early1700s.

Question 21

Therapeutic drug monitoringA 51-year-woman with epilepsy is admitted after suffering a seizure followingnon-compliance with her phenytoin. She admits to having problems at homeand was finding it difficult to continue to take her medication regularly. She isrestarted on phenytoin. How many half lives does it normally take for a drug toreach its steady state?A 1–2 half livesB 3–5 half livesC 10–11 half livesD 50–60 half livesE 100–150 half lives

Answer 21

B 3–5 half livesUsually, drugs take between 4 and 5 half lives to reach a steady state.The half life is the time it takes for the plasma concentration of thedrug to halve. Drugs such as phenytoin are monitored because underdosingwill lead to no effect but overdosing will lead to toxicity. Mostdrugs have a wide therapeutic window – that is the difference betweenthe minimum effective concentration and minimum toxic concentration.Drugs with narrow therapeutic windows may be suitable for drug monitoringto optimize treatment

Question 22

HypoglycaemiaA 67-year-old Indian man presents with irritability, sweating and tremor whichprogresses to stupor. The admitting doctor sends for a laboratory glucose whichcomes back at 2.2 mmol/L. The patient is resuscitated and given intravenousglucose.A history reveals that he does not suffer from diabetes, and his pastmedical history is remarkable only for vitiligo. On direct questioning he admitsto feeling increasingly more tired, particularly after returning recently fromIndia. His family arrive after which the doctor notices the patient’s unusuallydarker tan compared with his children. Further investigations reveal the patienthas low insulin and low C peptide concentrations. What is the most likely diagnosis?A Pituitary failureB Addison’s diseaseC Alcohol inducedD Glycogen storage diseaseE Medium chain acyl-CoA dehydrogenase deficiency (MCADD)

Answer 22

B Addison’s diseaseThis patient, presenting with hypoglycaemia, tiredness and hyperpigmentationwith an associated autoimmune history of vitiligo, mostprobably has adrenal failure (Addison’s disease (B)). The adrenal glandsare responsible for producing cortisol, aldosterone and sex hormones.Adrenal failure is potentially lethal due to the lack of cortisol, which isan important stress hormone as well as an important gluconeogenesisstimulant at times of hypoglycaemia. An important worldwide cause istuberculosis but in the developed world, autoimmunity is more likely.Autoimmune conditions often segregate as in this man with vitiligo,an autoimmune disease causing destruction of melanin in the skin. Thepatient has a tan as a by product of the lack of negative feedback in thehypothalamic–pituitary–adrenal axis. The hypothalamus releases cortisolreleasing hormone (CRH) to the anterior pituitary which in turn releasesACTH (adrenocorticotropic hormone). ACTH is produced from its precursormolecule POMC (pro-opiomelanocortin) which, when cleaved, alsoproduces MSH (melanocyte stimulating hormone). This accounts for theincreased tanning seen in patients with Addison’s.

Question 23

Acute pancreatitisA 56-year-old presents with sudden onset, severe epigastric pain which radiatesthrough to the back. The pain is relieved only partly by sitting forward and isassociated with nausea. The admitting doctor suspects pancreatitis and sendsfor a serum amylase which is greatly raised. A diagnosis of acute pancreatitis ismade. The following results come back following a blood test:Haemoglobin 14.5 g/dLWhite cells 14.2Na 148K 4.6Urea 14Creatinine 123Calcium 2.98 (corrected)Cholesterol 5.5Albumin 35 g/LGlucose 8.8 mmol/LWhich biochemical abnormality is not likely to be a consequence of acutepancreatitis?A Raised white cellsB Raised sodiumC Raised urea and creatinineD Raised calciumE Raised glucose

Answer 23

D Raised calciumHypercalcaemia is not a common consequence of acute pancreatitis,indeed hypercalcaenia is one of the causes of acute pancreatitis. Othercauses of pancreatitis can be remembered by the well known mnemonic‘GET SMASHED’:• Gallstones• Ethanol• Trauma• Steroids• Mumps• Autoimmune (polyarteritis nodosa)• Scorpion venom (Trinidadian scorpion)•Hypercalcaemia/Hypertriglyceridaemia/Hypothermia• Endoscopic retrograde cholangiopancreatogram• Drugs (including thiazides, azathioprine, valproate, oestrogens)

Question 24

Treatment of hyperkalaemiaA 76-year-old man presents following a fall and is diagnosed with a pubic ramusfracture which is treated conservatively. He has a background of chronic renalfailure and over the weekend starts to feel palpitations and lightheadedness. Anelectrocardiograph is performed which shows tenting of the T waves, suggestiveof hyperkalaemia. A blood test is performed which confirms the diagnosis. Whichof the following treatments does not lower plasma potassium levels?A Calcium resoniumB Sodium bicarbonateC Calcium gluconateD InsulinE Salbutamol

Answer 24

C Calcium gluconate Hyperkalaemia over 6.5 mmol/L is a medical emergency. Highextracellularpotassium levels increase cardiac excitability lowers thethreshold of fatal dysrhythmia. Classical electrocardiographicchangesinclude tall tented T waves, small P waves, widened QRS complexeswhich eventually become sinusoidal and can degenerate into ventricularfibrillation. Ten millilitres of 10 per cent calcium gluconate is the firstline medication given to anyone with hyperkalaemia. It does not changethe plasma potassium levels but stabilizes the myocardium to help preventfatal dysyhythmia. It does so by increasing the threshold potentialmaking the myocardium less excitable.

Question 25

Myocardial infarctionA 54-year-old man is admitted for an elective shoulder repair. The day before hissurgery he develops acute onset central crushing chest pain radiating to his leftarm and up the jaw. He is also sweaty and feels nauseous. He has a past medicalhistory of coronary artery bypass grafting and angina, and his father died froma heart attack aged 46. An electrocardiogram is performed which shows acuteST elevation in the inferior leads. He is diagnosed with acute coronary syndromeand treated appropriately. His surgery is delayed, but he presents with the samesymptoms 2 days later with further ST changes in the lateral leads. Which cardiacenzyme is most useful to confirm re-infarction?A Troponin IB Troponin TC Aspartate transaminaseD Creatine kinase muscle brain (MB)E Lactate dehydrogenase

Answer 25

D Creatine kinase muscle brain (MB)This question is difficult as it requires both knowledge of the relativesensitivities of cardiac enzymes and their relative timelines at whichthey stay raised after a recent infarction. CK MB (D) is the heart isoenzymecreatine kinase which rises about 6–12 hours post-infarctionand it usually peaks in concentration 24 hours later. It then reduces tonormal within 48–72 hours. It is very sensitive and is diagnostic if it is>6 per cent of total creatine kinase or the CK MB mass is >99 percentileof normal.It is very useful in detecting re-infarction because of its sensitivityand rapid return to normal levels compared with troponin I andT (A and B). Troponin is the most sensitive and specific test for myocardialinfarction and is traditionally taken 12 hours post-infarction.Troponin I is a better marker of myocardial infarction compared withtroponin T (Trop I: sensitivity and specificity of 90 per cent at 8 hoursand 95 per cent, respectively, trop T 84 per cent at 8 hours and 81 percent, respectively). However, troponin levels take up to 10 days to normalize,making their use in re-infarction soon after a primary infarctlimited. Another reason troponin is not the correct answer is that theyare not strictly speaking cardiac enzymes, but rather a structural proteinin the contractility mechanism. Interestingly, troponin T is also elevated in chronic kidney disease without troponin I elevation, for reasonsunknown.