eMedici - GenMed 1/3 Flashcards
Presentation - Eva is a 46-year-old woman who attends her local health centre for review of a blood test. Her last blood test showed a corrected total calcium level of 2.45 mmol/L and she had not had hypercalcaemia prior to this. A previous routine blood examination six months earlier was normal. She had presented to the clinic last week for a check-up, with a two month history of feeling vaguely unwell and tired. On the basis on the calcium result, her blood tests were repeated and the results are now available. Which one of the following most accurately reflects her corrected total calcium?
- 1.38 mmol/L
- 2.28 mmol/L
- 2.42 mmol/L
- 2.68 mmol/L
- 3.0 mmol/L
= 2.68 mmol/L
Which one of the following is the most likely cause for the hypercalcaemia?
- Sarcoidosis
- Vitamin D toxicity
- Primary hyperparathyroidism
- Spurious result
- Multiple myeloma
Primary hyperparathyroidism
Investigations - Primary hyperparathyroidism and malignancy account for >90% of hypercalcaemia cases. In patients with known malignancy, it is important to assess for disease progression and possible metastases. Multiple myeloma should be suspected in patients with hypercalcaemia and a history of acute renal failure, anaemia or pathological fracture. Urinary Bence-Jones protein and a serum paraprotein screen should be done in these cases. Vitamin D toxicity is uncommon in healthy patients, but should be considered when there is underlying renal impairment. Drugs such as lithium and thiazide diuretics may also contribute to hypercalcaemia. Eva’s only clinical complaint is a one month history of fatigue. A blood sample is sent for PTH level and vitamin D metabolites estimation. Eva’s PTH level is 9.9 pmol/L (N: 1.0-7.0) and her vitamin D level is normal.
DEXA scan & Urinary calcium/creatinine clearance ratio
Aetiology - Both primary hyperparathyroidism and familial hypocalciuric hypercalcaemia (FHH) will result in a high or inappropriately normal PTH level despite hypercalcaemia. PTH, which stimulates osteoclastic activity and works to increase serum calcium, should normally decrease in response to a high total calcium level. FHH is a rare autosomal dominant condition linked to mutations in the calcium sensing receptor gene (CASR). Patients with FHH are typically asymptomatic with a mild, longstanding hypercalcaemia and usually require no treatment. The underlying pathophysiology in FHH may be due to increased calcium reabsorption in renal tubules. Eva’s calcium/creatinine clearance ratio is 1.2 and a diagnosis of primary hyperparathyroidism is made.
= Parathyroid adenoma, Parathyroid hyperplasia, & Parathyroid carcinoma
Management - Primary hyperparathyroidism is most commonly due to an adenoma in one or two parathyroid glands (85%). Parathyroid hyperplasia is the next most common cause, and parathyroid carcinoma is more rarely implicated. A history of radiation to the head or neck, multiple endocrine neoplasia 1 (MEN-1) and older age are risk factors for developing primary hyperparathyroidism. Eva undergoes a DEXA scan that shows a bone mineral density (BMD) T-score of -1.4 at AP spine and -0.9 at total Hip. She has no fractures and her eGFR is >60 ml/min.
= Sestamibi scan and neck ultrasound
Which one of the following is the most appropriate next step in management?
- Intravenous rehydration
- Cinacalcet
- Calcitonin
- Pamidronate
- Parathyroidectomy
- Denosumab
= Intravenous rehydration
Risks - Eva’s hypercalcaemia responds well to intravenous rehydration and her total calcium level drops to 2.7 mmol/L. Her pancreatitis is managed conservatively and her abdominal pain resolves over the next couple of days. The option of parathyroidectomy is discussed once again and Eva is now keen to have the surgery. She is counselled on the risks associated with the procedure. Which of the following risks are specifically associated with parathyroidectomy?
= Vocal cord paralysis & Hypocalcaemia
What are the Clinical complications of hypercalcaemia?
What 4 things should you consider in the assessment of a patient with hypercalcaemia?
What is Jay’s Glasgow Coma Scale score?
= 13 - Jay’s opens his eyes to verbal commands (3), and is confused (4) but obeys motor commands (6) even though it takes several times to prompt him (6). A score of 15 would be the highest score and indicates normal neurological function.
Investigations - After being reassured that Jay’s airway is patent and protected you assess his breathing. He is breathing deeply, has a tachypnoea and the breath sounds and expansion are normal and equal over both lung fields. You also note a sweet smell on his breath and Jay’s mucous membranes are dry. The rest of his physical examination is unremarkable. With help from the nurse you both insert two large bore cannulae into Jay’s antecubital fossae and take some baseline bloods. Which of the following laboratory investigations would be appropriate at this stage?
= Full blood count, Serum biochemistry, Blood sugar level, Liver function tests, Arterial blood gas analysis, Blood and urine ketones, Urinary drug screen, Blood cultures.
Which of the following are potential explanations for these biochemical findings?
- Alcoholic ketoacidosis
- Anion gap acidosis
- Diabetic ketoacidosis
- Ethylene glycol toxicity
- Cocaine toxicity
= All except Cocaine toxicity
Fluid balance - Further results are obtained:
- Blood sugar *40mmol/L
- Ketones * 5.2mmol/L
confirming a diagnosis of diabetic ketoacidosis. Jay’s condition appears to be worsening. In addition to the Kussmaul respiration, he is dehydrated and lapsing in and out of consciousness. He needs prompt resuscitation.
Which one of the following combinations is required at this stage?
Intravenous fluids and insulin
Which of the following may have precipitated the diabetic ketoacidosis?
- Infection?
- Cocaine drug use?
- Non-compliance with medication?
- Insulin Overdose?
= Infection, Cocaine drug use, Non-compliance with medication.
Which of the following investigations are likely to be of value in determining the cause of his diabetic ketoacidosis?
- Urine culture
- Chest X-ray
- Glycosylated haemoglobin (HbA1c)
- Upper abdominal ultrasound
= Chest X-ray
Management - Jay is now transferred to the high dependency unit for close monitoring. Three hours after admission he has been given three litres of Hartmann’s and 20 units of actrapid insulin. A further litre of Hartmann’s is planned for the next two hours and the insulin infusion will continue at 5 units per hour. If on retesting it was found that his pH was now 7.1 and his blood glucose was 14 mmol/L what management plans would need to be instituted?
Add potassium to the intravenous fluid replacement regimen & Change the intravenous fluid regimen to include dextrose 5%
Which of the following diagnoses must be considered?
- Inflammatory bowel disease
- Carcinoma of the colon
- Infectious colitis
- Diverticulitis
- Irritable bowel syndrome
- Mesenteric ischaemia
History - With these possible diagnoses to consider, it is important to ask further questions to try and clarify the clinical picture. Select all the other questions that should be asked.
Quantitative and qualitative information on bowel motions, Family history of IBD, Constitutional Symptoms: weightloss, malaise, anorexia, Recent travel, Current medication.
Which initial investigations would be appropriate?
Colonoscopy - Lars is reviewed in the clinic after some investigation have been performed. He has a mild normocytic anaemia with an elevated white cells count, elevated ESR 30 mm/hr and C-reactive protein (CRP) 50 mg/ dL. Stool analysis is negative for common pathogens. Faecal calprotectin is raised. His liver function test and metabolic profile are unremarkable. A decision is made to refer Lars for a gastroenterological opinion. The gastroenterologist agrees that the likely diagnosis is ulcerative colitis and decides to perform an urgent colonoscopy the following week. Which of the following are the macroscopic features the gastroenterologist will look for to confirm this diagnosis?
= Backwash ileitis, Pseudopolyps, Broad-based ulcers, Inflammation that starts in the rectum and extends proximally.
Choose the first line treatment for ulcerative colitis.
= Oral and rectal 5-ASA (mesalazine)
Drug side effects - Lars is started on sulfasalazine (5-ASA) 2g twice daily and mesalazine enema 1g each night. He is monitored over the next 10 - 14 days, but despite complying with therapy, fails to achieve resolution of his rectal bleeding or improvement in diarrhoea. Lars is now commenced on oral prednisolone 40mg daily with the aim to reassess response to therapy again in the next 2-4 weeks. Prednisolone up to 1mg/kg/daily can be used in a tapering fashion usually over a 6-8 week period. Lars is warned about the potential side effects of this drug. Which of the following are recognised side effects of prednisolone?
Which of the following management options would be appropriate?
- Commence antibiotic therapy
- Intravenous fluid therapy
- Antidiarrhoeal agents
- Intravenous hydrocortisone 100mg 6 hourly
- Prophylactic anticoagulation
- Opioid analgesia
- Methotrexate
- Consider infliximab if the patient fails to respond to intravenous corticosteroid therapy
What additional conditions need to be excluded with this acute presentation?
Clostridium difficile colitis & CMV colitis - In an acute flare up of ulcerative colitis in a patient that has achieved substantial remission, other potential infections with cytomegalovirus (CMV) and Clostridium difficile need to be considered.
Surgery - Lars is admitted to hospital for treatment of an acute severe flare of his ulcerative colitis. The cause of this flare is not clear. During this admission his case is discussed with the surgeons with a view to colectomy. What are the indications for surgical management in ulcerative colitis?
Acute severe colitis that fails to respond to medical therapy Toxic dilatation of the colon (toxic megacolon) Refractory haemorrhage Perforation of the colon Failure of medical therapy to achieve sustained clinical remission Colorectal cancer risk in chronic colitis. Lars is reviewed by a surgeon to discuss the option of colectomy. Despite best practice medical management and regular infliximab infusions, Lars fails to achieve reduction of his inflammatory markers and improvement of his symptoms. Due to the patient’s inability to achieve substantial remission he elects to undergo a colectomy.
Which of the following are risk factors or diseases that could result in Franz’s jaundice?
- Haemolysis
- Intravenous drug use
- Recent antibiotic use
- Recent travel to South-East Asia
- Hydatid disease
- Heavy alcohol consumption
- Gall stones
- Inflammatory bowel disease
- Haemochromatosis
= Haemolysis, Intravenous drug use, Recent antibiotic use, Recent travel to South-East Asia, Heavy alcohol consumption, Gall stones, & Haemochromatosis.
History - Franz reports that his symptoms started ten days ago with dark, tea-coloured urine and his stools becoming paler in colour. More information needs to be obtained from the history. Which of the following pieces of information are likely to be of diagnostic value?
Important points on the patient’s medical history (and family history) that should be asked include:
- History of gallstones
- History of pancreatitis
- Known liver disease: cirrhosis, non-alcoholic fatty liver disease
- Known malignancy: either primary hepatic or biliary carcinoma, or known metastatic disease
- Autoimmune conditions: primary biliary cirrhosis, sclerosing cholangitis, autoimmune hepatitis, any other autoimmune conditions (inflammatory bowel disease, diabetes, thyroid disease, etc)
- Storage disorders: haemochromatosis, Wilson’s disease, a1-antitryptsin deficiency
- Haemolytic anaemias such as sickle cell anaemia.
- History of adverse drug reactions
Which of the following are stigmata of chronic liver disease?
- Spider naevi/angiomas
- Janeway lesions
- Gynaecomastia
- Head titubation
- Palmar erythema
- Chvostek sign
- Clubbing of the fingernails
- Testicular atrophy
- Koilonychia
- Ascites
Which of the diagnoses should be considered?
- Cholangitis
- Viral hepatitis
- Carcinoma of the head of the pancreas
- Drug-induced cholestasis
- Alcoholic liver disease
= Cholangitis & Drug-induced cholestasis
Investigations - From the information gained so far, it is quite likely that some intra-hepatic and post-hepatic causes should be considered. Some investigations will be needed to help determine the cause of Franz’s jaundice. Which of the following initial investigations should be undertaken?
A CT scan would not be a first-line investigation. Franz does not have risk factors for cancer and so cancer markers would be an inappropriate first-line investigation. In addition, cancer markers, such as alpha-feto protein and CA 19-9, have poor sensitivity and specificity and are more appropriately used for prognostication in patients with known disease.
Physiology - Blood samples are collected and arrangements are made for an ultrasound scan. The pathophysiology of jaundice will be considered. Bilirubin is the breakdown product of which blood component?
- Platelets
- Lymphocytes
- Globin
- Haem
= Haem
Erythrocytes are broken down by Kupffer cells in the liver and reticulo-endothelial system. Iron and globin are recycled. Haem is converted to biliverdin via haem oxygenase, and biliverdin is then reduced to bilirubin via bilirubin reductase.
Physiology - Which enzyme is responsible for bilirubin conjugation in the liver?
- Lactate dehydrogenase
- UDP-glucuronyltransferase
- Bilirubin transferase
- Beta-glucuronidase
= UDP-glucuronyltransferase
Physiology - Where does the majority of bile acid reabsorption occur?
- Distal colon
- Proximal colon
- Terminal ileum
- Duodenum
Terminal Ileum - About 95% of bile acids are reabsorbed in the terminal ileum. Conjugated bilirubin enters the gut then is reduced to urobilinogen which is absorbed by intestinal epithelium and returned to the liver via the enterohepatic circulation. Excess circulating urobilinogen is excreted by the kidneys, giving urine its straw colour.
Physiology - Pre-hepatic jaundice results in which combination of stool, urine and urinalysis findings (UA).
= Normal colour urine, no bilirubin on UA, positive urobilinogen on UA, normal stool.
Treatment - Whilst awaiting the results of the investigations, Franz wonders if there is something that he can use to help him with the itching. You have just finished revising the pathophysiology of jaundice when the nurse comes to tell you that Mr Ali is complaining about his itchy skin. The nurse would like you to prescribe some medication for his pruritus. Which of the following medications would be appropriate?
- Promethazine
- Cholestyramine
- Naloxone
= Any of these three medications could be considered.
Pathology - The results of the blood tests are now available. Which pathological process are they most consistent with? is suspected based on the pattern of LFTs?
- Pre-hepatic pathology
- Hepatocellular pathology
- Cholestatic pathology
- Isolated elevated bilirubin
= Cholestatic pathology
A hepatocellular disease pattern will result in a disproportionate elevation in the serum aminotransferases compared with the alkaline phosphatase, with or without elevation of serum bilirubin, and abnormal tests of synthetic function (albumin, prothrombin time). Common hepatocellular diseases associated with an elevated bilirubin and jaundice include viral and toxic hepatitis (including drugs, herbal therapies, and alcohol) and end-stage cirrhosis from any cause.
A cholestatic disease pattern will have a disproportionate elevation in alkaline phosphatase compared with the serum aminotransferases, with or without elevation of serum bilirubin (Image 1), and abnormal tests of synthetic function. The ALP must be twice the upper limit of normal combined with a significant elevation in GGT to be classified as cholestatic injury (Image 2). Cholestasis can be caused by either intra-hepatic or extra-hepatic pathologies. Common causes include partial bile duct obstruction, biliary cirrhosis (primary or secondary), sclerosing cholangitis (primary or secondary), and certain drugs.
Franz’s biochemical picture on his liver function tests suggests a cholestatic pathology. There is a significant rise in the alkaline phosphatase (ALP) and γ- glutamyl transpeptidase (GGT) which indicates either a post-hepatic obstructive cause (such as cholelithiasis) or intra-hepatic cholestasis (Image 3). Cholestatic injury is defined as an elevation of serum alkaline phosphatase (ALP) to greater than twice the upper limit of normal combined with a major elevation of γ-glutamyl transpeptidase (GGT) with minimal elevation of alanine transaminase (ALT) value. Alternatively, cholestasis is thought to be present when there is an increase in both ALT and ALP, but with an ALT:ALP ratio of < 2.
With a pre-hepatic pathology the conjugated bilirubin is significantly elevated indicating a hepatic or post-hepatic cause. In pre-hepatic pathologies, there would be an elevated unconjugated bilirubin with a normal conjugated bilirubin.
A hepatocellular pathology is unlikely as there is only a minor rise in alanine aminotransferase (ALT) comparative to alkaline phosphatase (ALP) and γ- glutamyl transpeptidase (GGT).
The liver function test shows derangement of liver enzymes as well as elevated bilirubin (Image 4) and therefore the pattern of Isolated elevated bilirubin is not present. Gilbert’s syndrome may give an isolated elevation of bilirubin.
Which one of the following combinations shows the common patterns of drug-induced liver injury?
- Hepatocellular, cirrhotic, obstructive
- Obstructive, inflammatory, mixed
- Hepatocellular, cholestatic, mixed-picture
= Hepatocellular, cholestatic, mixed-picture
Franz is reviewed the following day. Repeat liver function tests show bilirubin has risen, but his other liver enzymes are fairly stable. The other tests that were ordered all come back normal. This included a lipid profile, iron studies, thyroid function test, caeruloplasmin, and autoimmune antibodies (anti-nuclear antibody, anti-neutrophil cytoplasmic antibody, anti-mitochondrial antibody). With gastroenterological input, a (MRCP) is arranged to confidently exclude bile duct obstruction. It confirms no structural biliary or hepatic pathology. It is very likely that celecoxib is the culprit. What investigation could be ordered to confirm the diagnosis of drug-induced cholestasis?
- Fibroscan
- Fine-slice CT scan
- Magnetic resonance cholangiopancreatography (MRCP)
- Ultrasound-guided liver biopsy
- Antimitochondrial antibodies and IgG4 levels
= Ultrasound-guided liver biopsy
Which drugs can cause Drug-induced cholestasis?
Presentation - A 82-year-old man presents to his general practitioner with a three week history of increasing tiredness and fatigue. Ken has been off his food during this time and with a decreased appetite has become constipated. He thinks he might have lost a little weight over this time. In the last few days he has developed some discomfort in the right upper quadrant of his abdomen. Ken is normally in good health for his age and the only medications he takes ‘are tablets for my blood pressure and something for the cholesterol…’ He stopped smoking 15 years ago, with a 25 pack-year history. He enjoys a glass of wine most evenings. The only other illness of note is an episode of diverticulitis two years ago, which required a stay in hospital. He is a retired sheep farmer from Hamilton, Victoria. The doctor does not find anything abnormal on physical examination and thinks a CT scan would be appropriate. Several images from the study are shown. This shows two prominent filling defects in the liver. No other abnormalities are seen on the scan. In which of the liver segments are these lesions located?
The lesions are in segments IV and VI of the liver.
Aetiology
The Couinaud system of classification divides the liver into eight functional segments, each with its own arterial and portal venous inflow, venous outflow and bile drainage. Two lesions are clearly visible. Thought must be given to possible explanations for these lesions. Which of the following diagnoses need to be considered?
- Abscess formation
- Haemangioma
- Hydatid cysts
- Hepatocellular carcinoma
- Focal nodular hyperplasia
- Metastatic disease
- Hepatic cysts
= Metastatic disease
Aetiology
The Couinaud system of classification divides the liver into eight functional segments, each with its own arterial and portal venous inflow, venous outflow and bile drainage. Two lesions are clearly visible. Thought must be given to possible explanations for these lesions. Which of the following diagnoses need to be considered?
- Abscess formation
- Haemangioma
- Hydatid cysts
- Hepatocellular carcinoma
- Focal nodular hyperplasia
- Metastatic disease
- Hepatic cysts
= Metastatic disease
Investigations - The appearances are most suggestive of metastatic disease. The General Practitioner had also arranged some laboratory investigations. Which one of the following would be the most appropriate next step in management?
- Endoscopic retrograde cholangiopancreatography (ERCP)
- Fine needle aspiration biopsy
- Tumour markers
- Endoscopy and colonoscopy
- Magnetic resonance cholangiopancreatography (MRCP)
- Positron emission tomography (PET scan)
= Endoscopy and colonoscopy
Presentation - Mr. Finchurch is a 23-year-old indigenous man from outback South Australia who presents with 6 weeks of progressive dysphagia. Initially, solid foods such as sandwiches and pies were “sticking in his throat” and after two weeks he started to regurgitate his food. Mr Finchurch is now unable to swallow liquids and is concerned because he has lost 15kg of weight over the 6 weeks despite having a normal appetite. For the past three months, Mr. Finchurch has been weak and easily fatigued and has noticed a mild retrosternal burning pain. He has had no hoarseness of the voice, no cough and no haemoptysis. His past medical and surgical history is unremarkable and he takes no regular medications. He has no known allergies and no family history of atopy. Likely causes of this patient’s dysphagia include which of the following?
Eosinophilic oesophagitis, Achalasia, & Corrosive injury