Chem Path (Meded) Flashcards

Question

A 48 year old man is seen by his GP for tiredness. His medical history includes hypertension, previous myocardial infarction and a cerebral glioma, resected 5 years ago. He is currently on ramipril, bisoprolol, aspirin and atorvastatin. The GP sends off a basic set of bloods which return as follows: Na 128 mmol/L (135-145) K 4.1 mmol/L (3.5-5.5) Ur 4.5 mmol/L (2.5-6.7) Cr 82 mmol/L (70-150) The patient is euvolaemic and the doctor suspects a diagnosis of SIADH. What is the most likely cause of this patient’s SIADH? A. ramipril B. Chronic HTN 3. Atorvastatin 4. Glioma recurrence 5. Heart failure

Answer 1

4. Brain pathology is a known cause of SIADH (brain, lungs, pills)

Answer 2

SPASMODIC: S – Spasms (Trousseau's sign) P – Perioral parasthaesia A – Anxiety/Irritability S – Seizures M – Muscle tone increase (colic, dysphagia) O– Orientation impairment (i.e. confusion) D – Dermatitis I – Impetigo herpetiformis C – Chvostek's sign

Answer 3

1. Vitamin D deficiency -Malnutrition (i.e. osteomalacia) -Malabsorption (e.g. gastrectomy, short bowel syndrome, Coeliac disease, chronic pancreatitis) -CKD 2. Hypoparathyroidism -Post-parathyroidectomy, postradiation, autoimmune -Inherited (eg iron deposition in people with thalassaemia) -hypo/hypermagnasaemia -Pseudohypoparathyroidism (resistance to PTH) -DiGeorge syndrome 3. Hyperphosphataemia -Tumour lysis syndrome -Rhabdomyolysis -Phosphate administration 4. Acute pancreatitis (sequestration of serum calcium to proteins released dying pancreatic tissue) 5.Hypomagnesaemia 6. Acute alkalosis

Answer 4

Answer: Calcitriol (active form of vitamin D). In patients with CKD, final activation (hence vitamin D supplements must be in the active form)

Answer 5

E. Fluid restriction. Patient has SIADH (euvolaemic hyponatraemia with low serum osmolality, high urine osmolality and high urine sodium). 1st line treatment SIADH: fluid restriction (IV normal saline will make hyponatraemia worse in context of SIADH). When IV normal saline (0.9% NaCl) is given to a patient with SIADH, it can exacerbate hyponatremia because the extra sodium in the saline can cause a shift in fluids from the extracellular compartment (where sodium is higher) to the intracellular compartment (where sodium is lower). This shift can lead to further dilution of sodium in the blood, worsening the hyponatremia.

Answer 6

E. Fluid restriction. Patient has SIADH (euvolaemic hyponatraemia with low serum osmolality, high urine osmolality and high urine sodium). 1st line treatment SIADH: fluid restriction (IV normal saline will make hyponatraemia worse in context of SIADH). When IV normal saline (0.9% NaCl) is given to a patient with SIADH, it can exacerbate hyponatremia because the extra sodium in the saline can cause a shift in fluids from the extracellular compartment (where sodium is higher) to the intracellular compartment (where sodium is lower). This shift can lead to further dilution of sodium in the blood, worsening the hyponatremia.

Answer 7

B: TSH and cortisol are needed to exclude hypothyroidism and Addisonianism (both of which are causes of hyponatraemia). The paired serum and urine osmolalities are used to prove that the urine is inappropriately concentrated in the presence of dilute serum. The urine sodium is used to show that the sodium concentration is inappropriately high

Answer 8

D. Rhabdomyolysis Rhabdomyolysis develops due to damage to muscle tissue, causing an acute rise in creatine kinase. Muscle damage can be caused by exercise, crush injuries, drugs and infection. Treatment is with fluids or haemofiltration, and complications include hyperkalaemia, hypocalcaemia and death -hyperkalaemia--> cardiac arrest ccause

Answer 9

C. Hypokalaemia presents as above with generally a long PR, long QT and u waves which are positive deflections after the T wave. It should be managed with potassium replacement therapy the rate and method of which depend upon the severity of the loss. The maximum rate of potassium infusion off of a cardiac monitor (i.e. on a level 1 ward – not ITU or CCU) is 10mmol/h. This lady appears clinically dehydrated and therefore a standard regimen would be to add 40mmol of potassium to 1 litre of normal saline and run this IV over 4 hours

Answer 10

D. Oral calcium resonate In stable patients whose potassium is less than 6.0 mmol/L and ECG is normal, emergency treatment for hyperkalaemia is not required. Calcium resonium 15g QDS PO should be considered, apart from considering the underlying cause of the hyperkalaemia such as diet and medications (ACE-inhibitors, potassium-sparing diuretics, NSAIDs) Not: B IV calcium gluconate: This is part of the emergency treatment for hyperkalaemia, which is not indicated in this patient. This has no direct effect on the potassium levels, but stabilises the myocardium which is particularly sensitive to changes in potassium levels, especially when ECG changes such as peaked T waves, broad QRS, absent P waves or bradycardia are seen

Answer 11

D. Oral calcium resonate In stable patients whose potassium is less than 6.0 mmol/L and ECG is normal, emergency treatment for hyperkalaemia is not required. Calcium resonium 15g QDS PO should be considered, apart from considering the underlying cause of the hyperkalaemia such as diet and medications (ACE-inhibitors, potassium-sparing diuretics, NSAIDs) Not: B IV calcium gluconate: This is part of the emergency treatment for hyperkalaemia, which is not indicated in this patient. This has no direct effect on the potassium levels, but stabilises the myocardium which is particularly sensitive to changes in potassium levels, especially when ECG changes such as peaked T waves, broad QRS, absent P waves or bradycardia are seen

Answer 12

1. Serum magnesium – correct if low (Adequate magnesium intake is required for maintaining normal potassium levels, because hypomagnesaemia results in excess urinary excretion of potassium) 2. Aldosterone:renin ratio (if concomitant high BP); Primary hyperaldosteronism (Conn's) presents with hypertension and hypokalaemia.

Answer 13

hyperkalaemia -Digoxin increases intracellular calcium in myocardial cells indirectly by inhibiting the sodium–potassium ATPase pump in the cell membrane, causing the hyperkalaemia commonly seen in toxicity

Answer 14

hypocalcaemia -with a single gland removal the effects are likely to be transient due to suppression of the other parathyroid glands, but it may sometimes require treatment with oral calcium and vitamin D. Some patients can remain permanently hypocalcaemic, especially if more than one gland is operated on

Answer 15

Use the Fracture Risk Assessment Tool (FRAX) If the risk is low, bisphosphonates do not need to be given, but if the risk is between the two extremes, a DEXA scan should be carried out to guide the need for bisphosphonates

Answer 16

Use the Fracture Risk Assessment Tool (FRAX) If the risk is low, bisphosphonates do not need to be given, but if the risk is between the two extremes, a DEXA scan should be carried out to guide the need for bisphosphonates

Answer 17

hypocalcaemia, hyperphosphataemia, hyperkalaemia , hyperuricaemia

Answer 18

alcoholic hepatitis

Answer 19

viral hepatitis

Answer 20

- Biliary obstruction

Answer 21

advanced fibrosis or cirrhosis

Answer 22

toxins eg paracetamol, ischaemia eg ischaemic shock, viral hepatitis

Answer 23

Clotting – PT/INR Albumin Bilirubin

Answer 24

Bilirubin ALT, AST GGT ALP

Answer 25

Wilson's disease. worry if it's low

Answer 26

Hep B surface antigen, Hep C antibody

Answer 27

Wilson's disease

Answer 28

1. Gilbert’s syndrome: the most common cause. 2. Haemolysis: check a blood film, full blood count, reticulocyte count, haptoglobin and LDH levels to confirm.

Answer 29

if albumin function not preserved--> chronic

Answer 30

hepatocellular injury

Answer 31

marker of cholestasis

Answer 32

Toxins, viruses (acute viral hepatitis) and ischaemia

Answer 33

cholestatic picture

Answer 34

-Bony metastases or primary bone tumours (e.g. sarcoma) -Vitamin D deficiency -Recent bone fractures -Renal osteodystrophy

Answer 35

gliclazide

Answer 36

saxagliptin citagliptin, linagliptin, vildagliptine

Answer 37

exenatide, liraglutide lixisenatide

Answer 38

dapagliflozin, empagliflozin, canagliflozin

Answer 39

glargine, detemir

Answer 40

fatty liver

Answer 41

Carotid Ultrasound

Answer 42

adenocarcinoma

Answer 43

Enteropathy associated T-cell lymphoma (EATL) is a T-cell lymphoma

Answer 44

ALT (more than AST)

Answer 45

Alcohol: methanol, ethanol Sugars: mannitol, sorbitol Lipids: hypertriglyceridaemia Proteins: hypergammaglobulinaemia

Answer 46

1. Serum glucose – to exclude DM 2. Serum potassium – to exclude hypokalaemia 3. Serum calcium – to exclude hypercalcaemia 4. Plasma and urine osmolality 5. Water deprivation test (diagnosis of exclusion)

Answer 47

despite raised plasma osmolality, urine is dilute with a urine:plasma osmolality of < 2:1

Answer 48

Paired serum and urine osmolalities

Answer 49

muscle weakness, cramps, hypotonia

Answer 50

flattened/inverted T wave, prominent U wave, prolonged PR interval, ST depression

Answer 51

Increased potassium loss GI loss – diarrhoea, vomiting, high output stoma Renal loss – Conn’s syndrome, diuretics, congenital defects (Bartter and Gitelman syndromes) Increased cellular influx – insulin, beta agonists, refeeding syndrome, metabolic alkalosis

Answer 52

consider renal tubular acidosis (type 1 and 2), partially treated DKA

Answer 53

oral Sando-K

Answer 54

10 mmol/hour IV KCl, continuous ECG monitoring

Answer 55

tall tented T wave, small P wave, widened QRS, prolonged PR interval, sine wave

Answer 56

Artefact – haemolysis Iatrogenic – massive blood transfusion, excessive K+ therapy Reduced excretion – renal disease, aldosterone deficiency, drugs (potassium-sparing diuretics, ACEi, ARB) Increased cellular release – metabolic acidosis, tissue breakdown

Answer 57

1. recheck K+ levels if >6.5mmol/l (haemolysis) 2. 10mls 10% calcium gluconate (cardioprotective) 3. 100mls 20% dextrose (stimulates insulin release) and 10 units short-acting insulin eg actrapid 4. nebulised salbutamol 5. in some cases consider calcium resonium 15g or 30g PR (binds potassium in gut)

Answer 58

primary: suspect Men1 /2a syndrome tertiary: late stage CKD (autologous vitamin D)

Answer 59

paraesthesia (peri-oral), arrhythmia (long QT), convulsions, tetany (Trousseau’s sign), spasm (Chvostek’s sign) The symptoms can be recalled by the mnemonic "CATs go numb" - convulsions, arrhythmias, tetany, and numbness in the hands and feet and around the mouth.

Answer 60

Hypoparathyroidism – DiGeorge (primary), post-thyroidectomy (secondary), low magnesium Vitamin D deficiency

Answer 61

ECG (bedside), bloods (Mg, phosphate, PTH level, ALP), imaging (consider DEXA if # history)

Answer 62

-Mild (> 1.9 mmol/L, no Sx) – Oral calcium, vitamin D supplement -Severe (< 1.9 mmol/L, Sx present) – IV calcium gluconate

Answer 63

Low PTH – malignancy (PTHrP, bony mets, multiple myeloma), hyperthyroidism, hypoadrenalism, sarcoidosis, thiazides, vitamin D excess

Answer 64

Raised PTH – primary and tertiary hyperparathyroidism How to differentiate – late-stage CKD in tertiary Suspect MEN1 and 2a syndrome if primary

Answer 65

1. Osteomalacia 2. Secondary hyperparathyroidism 3. Osteoporosis 4. Primary hyperparathyroidism 5. Parathyroid carcinoma Osteomalacia – Vitamin D very low need for calcium absorption, calcium will fall the most 2° PTH – raised PTH 2° to low Ca (short term) (usually in chronic kidney disease, unable to retain Ca) Osteoporosis – calcium normal 1° PTH - mainly due to parathyroid adenoma/hyperplasia, PTH secretion less than carcinoma Parathyroid carcinoma – highest PTH - autonomous release of Ca2+ (lack of -ve feedback)

Answer 66

myeloma screen, TFTs (hyperthyroidism can cause bone resorption), cortisol level (to rule out Addison's)

Answer 67

Acute: IV 0.9% NaCl +/- diuretics Medical: Bisphosphonates (malignant hypercalcaemia), cinacalcet Surgical: Parathyroidectomy if parathyroid adenoma

Answer 68

vitamin D deficiency

Answer 69

parathyroid adenoma

Answer 70

malignancy

Answer 71

The most common causes of secondary hyperparathyroidism are kidney failure and vitamin D deficiency.

Answer 72

Prehepatic – haemolytic anaemia, ineffective erythropoiesis Key – absent conjugated bilirubin, absent urine bilirubin

Answer 73

Hepatic – hepatocellular dysfunction, impaired conjugation, impaired bilirubin uptake

Answer 74

Post-hepatic (obstruction) – stones, pancreatic cancer Key – dark urine (raised urobilinogen), pale stool (low stercobilinogen

Answer 75

Increased haemolysis – extravascular (spherocytosis), intravascular (haemoglobinuria) Impaired hepatic uptake – drugs (contrast, rifampicin) Impaired conjugation – Gilbert’s syndrome (deficiency of UDP-glucuronyl transferase), Crigler-Najjar syndrome (absolute deficiency)

Answer 76

Hepatocellular dysfunction – congenital, infections, toxins, autoimmune, neoplasm, vascular Decreased hepatic excretion – congenital (Dubin-Johnson, Rotor syndrome)

Answer 77

Prothrombin time

Answer 78

troponin creatine kinase (MB) AST LDH

Answer 79

Men2 syndrome

Answer 80

-Multiple endocrine neoplasia (predispositions to develop cancer) MEN1 (3Ps): Pituitary, Pancreatic (e.g. insulinoma), Parathyroid adenoma MEN2a (2Ps, 1M): Parathyroid hyperplasia , Phaeochromocytoma, Medullary thyroid MEN2b (1P, 2Ms): Phaeochromocytoma, Medullary thyroid, Mucocutaneous neuromas (& Marfanoid) -AUTOSOMAL DOMINANT -Men 1 (parathyroid adenoma), Men2a (parathyroid hyperplasia)

Answer 81

autosomal dominant

Answer 82

adrenaline causes hypokalaemia

Answer 83

C. The patient has a raised anion gap metabolic acidosis. This patient’s anion gap is calculated as follows: [141 + 4.9] – [104 + 12] = 29.9mmol/L. He has risk factors for chronic kidney disease: age, diabetes and hyertension and he also has a clear reason to have a pre-renal decompensation: poor oral intake. The patient has several features of renal failure (e.g. confusion, pleuritic pain, signs of fluid overload) which is a serious complication of acute kidney injury and leads to a raised anion gap metabolic acidosis Not: D: If severe it would lead to a respiratory acidosis rather than a metabolic acidosis. It is also not consistent with the history

Answer 84

C. The patient has a raised anion gap metabolic acidosis. This patient’s anion gap is calculated as follows: [141 + 4.9] – [104 + 12] = 29.9mmol/L. He has risk factors for chronic kidney disease: age, diabetes and hyertension and he also has a clear reason to have a pre-renal decompensation: poor oral intake. The patient has several features of renal failure (e.g. confusion, pleuritic pain, signs of fluid overload) which is a serious complication of acute kidney injury and leads to a raised anion gap metabolic acidosis Not: D: If severe it would lead to a respiratory acidosis rather than a metabolic acidosis. It is also not consistent with the history

Answer 85

D. IV calcium gluconate Given that the patient is symptomatic and is experiencing distressing spasms it is appropriate to rapidly correct her hypocalcaemia with IV calcium Not: C. Encourage increased oral calcium and Vitamin D intake Although this is important in long term prevention of hypocalcaemia in hypoparathyroid patients, it does not tackle the immediate problem

Answer 86

A. 4 hour IV infusion of 1L 0.9% saline containing 40mmol potassium chloride As the patient is showing ECG changes it is prudent to initiate intravenous therapy. The infusion rate is used to avoid potassium being administered too fast. Saline is the preferable solute for the potassium chloride because it does not affect insulin production Not B: 40mmol potassium chloride IV bolus As the patient is showing ECG changes it is prudent to initiate intravenous therapy. The infusion rate is used to avoid potassium being administered too fast. Saline is the preferable solute for the potassium chloride because it does not affect insulin production

Answer 87

C. This is the correct answer. This patient has hypercalcaemia due to bone metastases to the hip, secondary to a lung malignancy (suggested by her dyspnoea and smoking history). Hypercalcaemia caused by bone metastasis is accompanied by hyperphosphataemia and raised ALP. PTH may be normal (or low if PTH-related peptide (PTHrP) is produced) Not B: Sarcoidosis Whilst increasing dyspnoea, especially on exertion, coupled with hypercalcaemia (causing thirst and polyuria), are suggestive of sarcoidosis, you would expect a raised serum Vitamin D due to hydroxylation of vitamin D by sarcoid granulomas. The resultant hypercalcaemia would then supress PTH

Answer 88

B. 1L normal saline with 40mmol potassium chloride given over 4 hours This is correct. The patient is severely potassium deficient so needs IV potassium. On top of that she will also be fluid deplete from her ongoing losses. It is therefore wise to replace the potassium as quickly as is safe (10mmol/hour) while replacing fluids reasonably quickly Not D: oral Sandok for 3 days The patient has ongoing vomiting therefore will not keep this down

Answer 89

A. Calcium This is the correct answer. Iatrogenic hypocalcaemia is not uncommon after thyroidectomy affecting the parathyroid glands. ECG changes consistent with hypocalcaemia include prolonged QT interval

Answer 90

C. IV haematin This is correct. The patient has the features of an acute attack of intermittent porphyria (abdominal pain, vomiting, seizures, red urine and high porphobilinogen). Part of the treatment of severe attack should be IV haematin which reduces the activity of 5-aminolevulinic acid synthase 1 which produces 5-ALA and porphobilinogen

Answer 91

D. This is the correct answer. ESR is useful in monitoring the progression of rheumatoid arthritis and when ESR is raised in an acute flare, it remains raised for up to one week after the inflammation settles Not B: Anti-CCP is highly sensitive for diagnosing rheumatoid arthritis but is not an acute phase reactant

Answer 92

B. Central diabetes insipidus This is the only diagnosis that unifies all of the clinical findings and workup results: a polyuria of more than 3L of urine a day, a raised plasma osmolality and reduced urinary osmolality (low sodium, high water), all of which are reversed with desmopressin administration. Normally, a water deprivation test is performed first before desmopressin is administered to exclude psychogenic polydipsia as a differential. However, given the higher than normal serum sodium (> 145 mmol/L), this is adequate evidence of a water deprived state, and the water deprivation test is not required. Carrying this out regardless is dangerous for patients with diabetes insipidus, and can result in rapid circulator collapse and shock as their urine output remains markedly raised Not C: SIADH Such patients would have hyponatraemia (< 135 mmol/L), a low serum osmolality (< 275 mOsmo/kg) and a raised urinary osmolality (> 100mOsmo/kg)

Answer 93

normal or primary polydipsia

Answer 94

central DI

Answer 95

nephrogenic DI

Answer 96

Paired serum and urine osmolalities

Answer 97

B. Asymptomatic Paget's mainly affects elderly people and is caused by increased bone cell turnover - which can be asymmetrical, often larger in size. Bones affected by Paget's have altered mechanical properties so are more likely to fracture. 90% of patients with Paget's disease however are asymptomatic so it is often picked up as a coincidental finding. The diagnosis is primarily radiological and the feature include; lytic lesions, cortical thickening, loss of corticomedullary distinction, thickening of long bones, sclerosis and an increase in bone size Not D: Pain tends to be multifactorial in origin, either due to fractures, nerve compression or because of 'growing' pains. The answer is incorrect as it is not the commonest clinical feature

Answer 98

hyperkalaemia as the kidneys would usually maintain potassium homeostasis by excreting any excess.

Answer 99

A. Treat for osteoporosis This is the correct answer. A score which shows a 10 year fracture risk of greater than 10% requires further assessment using a bone density scan. Osteoporosis is diagnosed when patients have a bone density score of less than 2.5 standard deviations below the average value in a cohort of young patients

Answer 100

D. Diabetic ketoacidosis This patient’s anion gap is calculated as follows: [140 + 4.5] – [104 + 16] = 24.3mmol/L. This is raised. Diabetic ketoacidosis is the correct answer because the exhibits clinical features of DKA including nausea, vomiting, abdominal pain and dehydration. The introduction does not state that the patient has polyuria/polydipsia but the age of the patient and the fact that DKA is a well known cause a raised anion-gap acidosis makes this the best answer Not A. Uraemia will cause a raised anion gap acidosis. However, although the patient does have an acute kidney injury, it is not severe enough to support a diagnosis of uraemia. Furthermore, the patient shows no evidence of either uraemic pericarditis or encephalopathy

Answer 101

1. Analgesia 2. Bisphosphonates (eg. alendronic acid, pamidronic acid) - inhibit osteoclast activity 3. Typically treatment lasts 6 months and following completion bone activity may return to normal 4. Monitor at regular 6 or 12 month intervals for recurrence

Answer 102

brain, lung, pills, malignancy (eg small cell lung cancer:ACTH, ADH)

Answer 103

small square: 40ms large square: 200ms SMALL square (1mm) = 0.04 sec (40ms) 5 SMALL squares (5mm) = 1 LARGE square = 0.2 sec (200ms) 5 LARGE squares = 1 second. QTc is prolonged if > 440ms in men or > 460ms in women

Answer 104

electrolytes: hypomagnesiumia, hypokalaemia, hypothermia

Answer 105

B. Raised alkaline phosphatase levels: This is due to increased bone turnover (osteoblastic activity in particular) as a result of raised parathyroid levels. It is likely this patient has progressed from secondary to tertiary hyperparathyroidism, as persistent secondary hyperparathyroidism leads to autonomous production of parathyroid hormone, regardless of negative feedback from calcium levels Not: C Low calcium levels The hallmark of progression from secondary to tertiary hyperparathyroidism is the increase in calcium levels, due to the negative feedback from calcium levels no longer having an effect on parathyroid hormone levels. Tertiary hyperparathyroidism is defined as the presence of raised calcium, phosphate and parathyroid hormone levels Not E: Reduced phosphate levels Phosphate levels are generally raised in tertiary hyperparathyroidism. Although increased parathyroid levels generally lead to a net reduction in phosphate levels, such as in primary hyperparathyroidism, this is likely outweighed by decreased phosphate excretion as a result of reduced renal function. Tertiary hyperparathyroidism is defined as the presence of raised calcium, phosphate and parathyroid hormone levels

Answer 106

-80% single parathyroid adenoma -15% parathyroid hyperplasia/multiple parathyroid adenomas -0.5% carcinomas (most carcinomas non-functional) -Men1 (adenoma) and 2 (hyperplasia)

Answer 107

-Ca: high -phosphate: low (PTH causes phosphate excretion from kidneys) -vitamin D: normal -ALP: normal/high -PTH: high/normal

Answer 108

-CKD -osteomalacia (long term), vitamin D deficiency -malabsorption syndromes

Answer 109

-Ca: low -vitamin D: normal/low (CKD; less active vitamin D/vitamin D deficiency) -phosphate: high -ALP: high -PTH: high

Answer 110

-prolonged secondary hyperparathyroidism (causing unregulated secretion of PTH) -kidney transplant

Answer 111

-Ca: high/normal -vitamin D: normal/low (CKD; less active vitamin D/vitamin D deficiency) -phosphate: high/low -ALP: high -PTH: high (usually everything high except vitamin D)

Answer 112

Chimpanzee

Answer 113

Management focuses on preventing this from occurring through giving prophylactic allopurinol and in some cases a recombinant urate oxidase, rasburicase. Good hydration should be maintained.

Answer 114

Tumour lysis syndrome is caused by the release of uric acid from cells that are being destroyed by chemotherapy. The uric acid can form crystals in the interstitial tissue and tubules of the kidneys and causes acute kidney injury. Allopurinol or rasburicase are used to reduce the high uric acid levels. Other chemicals such as potassium and phosphate are also released so these need to be monitored and treated appropriately. High phosphate can lead to low calcium, which can have an adverse effect, so calcium is also monitored.

Answer 115

include nausea, vomiting and muscle pain

Answer 116

Important investigations include: U&E (potassium and phosphate are typically raised), calcium (low), uric acid (raised), and ECG (metabolic abnormalities e.g. hyperkalaemia may precipitate life-threatening arrhythmias).

Answer 117

B. IV antibiotics and fluids This is correct. The patient has all the features of urosepsis and therefore should get IV antibiotics for the infection and fluids to combat the septic shock. The raised troponin is a perfect example of an inappropriately requested investigation given the patient has no chest pain or ECG changes Not: A: Aspirin, clopidogrel and treatment dose low molecular weight heparin Although this patient has a raised troponin it is almost certainly secondary to sepsis because the patient does not have chest pain, has a normal ECG and has a static troponin. Therefore, the is no need to treat this as acute coronary syndrome

Answer 118

D. Recent transsphenoidal pituitary surgery Water deprivation test: cranial DI urine osmolality after fluid deprivation: low urine osmolality after desmopressin: high This is a case of cranial diabetes insipidus. Despite 8 hours of water deprivation, the patient's urine is still incredibly dilute (urine osmolalility >100mOsml/kg) suggesting a water concentration issue with vasopressin. The fact that the urine osmolality increments wonderfully with desmopressin, it suggests that there is a vasopressin production issue, implying cranial diabetes insipidus. Recent transsphenoidal is a well-documented cause for cranial diabetes insipidus and would be most relevant given the water deprivation findings above. (brain, lungs, pills) Now to look at the other options. Recent AKI would be important in the polyuric phase of an AKI, however, these results suggest a vasopressin issue given the marked response to desmopressin. Concurrent lithium use is relevant for nephrogenic diabetes insipidus. Primary hyperparathyroidism with subsequent hypercalcaemia is another well-documented cause for nephrogenic diabetes insipidus. Schizophrenia is one of the most common associations with psychogenic (primary) polydipsia.

Answer 119

1. Increased loss of HCO3, such as; -Diarrhoea -High output ileostomy -Ureterosigmoidostomy I-mpaired kidney resorption (e.g. acetazolamide treatment) -Renal tubular acidosis type 2 -Hypoaldosteronism -Adrenal insufficiency -Mineralocorticoid receptor block (e.g. spironolactone treatment) 2. Increased production of H+, such as; -Toluene (crude oil/mining) poisoning -Lysine or arginine administration (found in total parental nutrition) 3. Decreased excretion of H+, such as; -Renal tubular acidosis types 1 and 4

Answer 120

A. Bendroflumethiazide Hyponatraemia occurs more commonly with thiazide diuretics, although it has also been described in association with furosemide and spironolactone Not: E: spironolactone A weak potassium sparing diuretic that works as an anti-mineralocorticoid. It is often used in congestive heart failure and cirrhosis. It’s side effects include gynecomastia and hyperkalemia. It is less likely to cause hyponatraemia compared to a thiazide-like diuretic Not D: Acetazolamide: A weak potassium sparing diuretic. It is most often used for high altitude sickness and idiopathic intracranial hypertension. It works by inhibiting carbonic anhydrase and leads to excess ions excreted in the proximal tubule of the kidney. Although it can cause hyponatremia it is less likely than bumetanide

Answer 121

There may be a clear cause of hyponatraemia such as heart failure or vomiting. When the cause is not well-defined, a number of tests are required to confirm/exclude Syndrome of Inappropriate Anti-Diuretic Hormone (SIADH): 1. Urea and Electrolytes (while not on diuretics) - to confirm hyponatraemia and to exclude mixed electrolyte abnormalities (not seen in SIADH) 2. Urine and plasma paired osmolalities (while not on diuretics) - to demonstrate the inappropriate concentration of the urine 3. Urine sodium (while not on diuretics) - to demonstrate sodium wasting in the kidneys 4. Urine dip - to screen for infection and glomerular pathology 5. TSH and cortisol - to exclude hypothyroidism (rare cause of euvolaemic hyponatraemia) and Addison's disease

Answer 122

1. Adrenal adenoma (Conn's Syndrome) 2. Bilateral adrenal hyperplasia 3. Familial hyperaldosteronism 4. Adrenal carcinoma

Answer 123

1. Hypertension 2. Hypokalaemia 3. Metabolic alkalosis

Answer 124

Patients can present with polyuria, polydipsia, lethargy and headaches. There is also an association with osteoporosis. Investigations 1. FBC/UE/LFT 2. ESR 3. Bone profile 4. Thyroid function tests 5. Chest X-ray 6. ECG 7. Aldosterone/renin ratio 8. CT/MRI to locate adrenal lesions 9. Selective adrenal venous sampling (Gold Standard)

Answer 125

Treatment of aldosterone excess is to identify the underlying cause, often using specialist imaging or adrenal venous sampling and then to surgically remove the affected adrenal gland, or if bilateral adrenal disease then to use medication such as potassium sparing diuretics (e.g. Amiloride, Spironolactone, Eplerenone).

Answer 126

C. Bumetanide This patient's ECG shows features of hypokalaemia, notably flattened and even inverted T-waves (seen best in leads V5 and V6), ST-segment depression (seen best in leads II, III and aVF), and most tellingly, prominent U waves (additional uptick waveform following the T-wave, seen best in the precordial leads). Bumetanide is a loop diuretic, a potent ("high-ceiling") diuretic which inhibits the NKCC2 transporter in the thick ascending loop of Henle, which is responsible for Sodium, Chloride and Potassium reabsorption. Increased delivery of Sodium to the collecting ducts results in increased Sodium/Potassium exchange via the ENaC transporter, leading to further Potassium loss. Therefore, a notable and common side-effect of loop diuretics is hypokalaemia. This patient has likely been treated with Bumetanide for acute pulmonary oedema

Answer 127

they can elevate the calcium levels in the samples (can also cause pseudohyperkalaemia)

Answer 128

Difficult or traumatic venepuncture can lead to mechanical haemolysis of red bloods cells leading to massive release of potassium. This can lead to inaccurate measure of the serum potassium if not checked for by the lab

Answer 129

putting a sample on ice reduces the risk of pseudohyperkalaemia from haemolysis

Answer 130

Omeprazole is a very common cause of hypomagnesaemia. This occurs via inhibition of gut absorption of magnesium

Answer 131

B. Sertraline The patient has the clinical features of SIADH (euvolaemic hyponatreamia with low serums osmolality, high urine osmolality and high urine sodium). Selective serotonin reuptake inhibitors are a well recognised drug cause of SIADH Amlodipine, ranitidine=rare causes of SIADH. other drugs in GORD eg omeprazole=more common in SIADH ramipril (ACE inhibitor) causes hyperkalaemia

Answer 132

Indapamide is a thiazide-like diuretic. Thiazide diuretics decrease blood pressure by blocking the Na/Cl cotransporter in the distal convoluted tubule. This results in an increased excretion of sodium and chlorine (and therefore water) in the urine, leading to a decreased blood volume and therefore blood pressure.

Answer 133

(GFR: outside inside glomerulosa, fasciculata & reticularis: salt, sugar, sex: mineralocorticoids, glucocorticoids, androgens vs medulla: catecholamines eg adrenaline/noradrenaline and dopamine)

Answer 134

hyperparathyroidism (parathyroid adenoma/hyperplasia )

Answer 135

Xanthine oxidase

Answer 136

B3 (niacin)

Answer 137

3Ds: dementia, dermatitis, diarrhoea

Answer 138

ATP7B (chromosome 13); encodes copper transporting ATPase expressed on canalicular membrane therefore decreases biliary copper excretion and deposits in liver, CNS & iris (Kayser Fleischer rings) -deficiency of caeruloplasmin (a copper-containing protein produced by the liver that helps to transport copper in the blood)

Answer 139

ACE inhibitors and ARBs reduce proteinuria by lowering the intraglomerular pressure, reducing hyperfiltration. These drugs tend to raise the serum potassium level and reduce the glomerular filtration rate

Answer 140

Type 1 Renal Tubular Acidosis Renal tubular acidosis are a series of heterogenous conditions which describe the failure of the body to acidify the urine. This, therefore, leads to an intravascular metabolic acidosis. There are four clinically significant types of renal tubular acidosis. Type 1 (Distal Renal Tubular Acidosis) Profound metabolic acidosis Hypokalaemia Renal stones (more alkaline urine means calcium precipitates more easily) Failure of alpha intercalated cells to secrete H+ and resorb K+ Type 2 (Proximal Renal Tubular Acidosis) Moderate metabolic acidosis Hypokalaemia Failure of proximal tubular cells to reabsorb HCO3- Type 3 Exists but is very niche even for path Type 4 (Hyperkalaemic RTA) Adrenal failure Mild reduction in serum pH Hyperkalaemic Caused by a deficiency of aldosterone

Answer 141

Probenecid The aim of treatment in an acute flare up of gout is to reduce inflammation. First line is NSAIDs (eg. Diclofenac). Colchicine is also useful in reducing inflammation and acts by inhibiting polymerisation of tubulin to reduce migration of neutrophils. Glucocorticoids can be injected or given orally. During the intervals between acute gout, the aim is to reduce urate levels. Patients should be advised to drink plenty of water and avoid dietary sources high in purines such as port wine and organ meats. Medications should also be reviewed and diuretics stopped. Allopurinol inhibits the enzyme xanthine oxidase to reduce urate synthesis, and Probenecid increases fractional excretion of uric acid.

Answer 142

1 alpha hydroxylase The granulomatous tissue seen in sarcoidosis has been known to increase activation of vitamin D via production of the enzyme 1 alpha hydroxylase normally expressed in the kidney. The raised vitamin D leads to an increase in absorption of calcium from the gut causing hypercalcaemia. Production of PTH-related-peptide (PTHrP) is another mechanism by which the granulomatous tissue can cause hypercalcaemia.

Answer 143

1. Addison's disease 2. Bicarbonate loss (diarrhoea, laxative abuse, Renal Tubular Acidosis) 3. Chloride gain (Sodium Chloride 0.9% infusion) 4. Drugs (acetazolamide)

Answer 144

Addison's disease Step 1 - Identify the metabolic acidosis (+- any respiratory compensation) A low pH, low base excess low bicarbonate, normal/low pCO2 characterises this. Step 2 - Calculate the anion gap Recall that the anion gap is (Na + K) - (Cl + HCO3) and is normally 14-18mmol/L Causes of a raised anion gap metabolic acidosis are best remembered by GOLDMARK (MUDPILES is old) G: Glycols (ethylene glycol and propylene glycol) [overdose] O: Oxoproline [chronic paracetamol use, usually malnourished women] L: L-lactate [sepsis] D: D-lactate [short bowel syndrome] M: Methanol [overdose] A: Aspirin [overdose. Initially causes respiratory alkalosis but in moderate/severe overdose causes metabolic acidosis] R: Renal failure K: Ketoacidosis [DKA, alcoholic, starvation] Are you not sure which of the causes of a raised anion gap acidosis are present? Move to step 3. Causes of a normal anion gap metabolic acidosis. Bicarbonate is lost and replaced with Chloride leading to a normal anion gap Addison's disease Bicarbonate loss (diarrhoea, laxative abuse, Renal Tubular Acidosis) Chloride gain (Sodium Chloride 0.9% infusion) Drugs (acetazolamide) If the history matches any of these causes then you have your answer Step 3 - still unsure? If it's still not clear what is going on with a raised anion gap metabolic acidosis, then the osmolar gap may explain what's going on. Osmolality (measured by lab) - Osmolarity (calculated by you) Calculated osmolality = 2x(Sodium +Potassium) + Glucose + Urea Professor Meeran uses an outdated osmolar gap equation including potassium - in clinical practice 2xNa + Glucose + Urea is used instead This should be less than 10. If it is greater than 10 then it suggests the presence of something that our tests cannot measure directly. For instance, an unexplained metabolic acidosis (usually in the context of overdose) with a raised anion and raised osmolar gap can only be due to glycol, ethanol, mannitol or methanol poisoning.

Answer 145

Fanconi syndrome Fanconi syndrome (NB: Fanconi anaemia is something else) is an inherited or acquired condition where there is almost complete failure of the proximal convoluted tubule in the kidney to reabsorb molecules. Causes (there are many, but for exams these are classical) Congenital Wilson's disease (To be even more unhelpful, Wilson's is also associated with Type 1 Renal Tubular Acidosis) Tetracyclines Multiple Myeloma Lead poisoning Symptoms + Signs Polyuria, polydipsia and dehydration (due to glucosuria) Growth failure (in children) Metabolic acidosis (Type 2 Renal Tubular Acidosis) Hypokalaemia Proteinuria Hyperuricosuria

Answer 146

Hyperosmolar Hyperglycaemic State Hyperosmolar Hyperglycaemic State (HHS) is a complication of type 2 diabetes resulting from significantly raised blood glucose resulting in high serum osmolality and leading to severe dehydration. This occurs without significant ketoacidosis but still has a high mortality. Individuals may present unconscious explaining why HHS is also known as Hyperglycaemia Hyperosmolar Nonketotic Coma (HONK). HHS usually develops over a few days and may be precipitated by an infection. Treatment is aimed at rehydration and reducing blood glucose safely. Serum osmolality must be reduced slowly and monitored frequently to avoid causing cerebral oedema.

Answer 147

cholesterol esters Acyl-CoA cholesterol acyltransferase (ACAT) is found in nearly all cells and catalyses the esterification of cholesterol. ACAT therefore plays an important role in bile acid synthesis and is also involved in the process of atherosclerosis.

Answer 148

tertiary hyperparathyroidism Hypocalcaemia on a background of untreated chronic kidney disease may result in secondary hyperparathyroidism with hyperplasia of the parathyroid glands. Renal transplantation can correct the underlying kidney disease causing the hypocalcaemia but the hyperplasia of the parathyroid glands may persist after transplant. This results in an inappropriately high level of PTH and subsequent hypercalcaemia. This is known as tertiary hyperparathyroidism.

Answer 149

Evolocumab LDL receptor mutations are a common genetic defect underlying Familial hypercholesterolemia. The LDL receptor usually removes LDL from the circulation and so the disorder results in high levels of LDL predisposing to early atherosclerotic disease. The most potent LDL lowering drug in this setting is evolocumab - a PCKS9 inhibitor.

Answer 150

Familial Hypercholesterolemia Arcus senilis (cornea senilis) are lipid deposits that appear as rings on the outer region of the cornea

Answer 151

Microsomal triglyceride transfer protein Lomitapide is a lipid lowering medication used in the treatment of Familial Hypercholesterolemia. Lomitapide acts by inhibiting Microsomal triglyceride transfer protein (MTP), thereby blocking the release of VLDL from the liver. This in turn leads to reduced LDL levels.

Answer 152

Approximately 40% of serum Ca2+ is bound to the circulating plasma protein albumin. 50% of serum Ca2+ is free (ionised) and this makes up the active component. The concentration of this active component is tightly controlled. If the plasma albumin concentration falls the total calcium level will appear low but the free calcium level will remain the same. Calculating a corrected calcium level allows us to check if the free calcium concentration is normal in the presence of an abnormal albumin level. Corrected Ca = serum Ca × 0.02 × (40 - serum albumin g/L)

Answer 153

conjugated bilirubin The van den Bergh reaction is used to measure serum bilirubin via fractionation. The direct reaction measures conjugated bilirubin whereas a complete reaction measures total bilirubin. The indirect reaction refers to the difference between these two and measures unconjugated bilirubin.

Answer 154

Colchicine The aim of treatment in an acute flare up of gout is to reduce inflammation. First line is NSAIDs (eg. Diclofenac). Colchicine is also useful in reducing inflammation and acts by inhibiting polymerisation of tubulin to reduce migration of neutrophils. Glucocorticoids can be injected or given orally. During the intervals between acute gout, the aim is to reduce urate levels. Patients should be advised to drink plenty of water and avoid dietary sources high in purines such as port wine and organ meats. Medications should also be reviewed and diuretics stopped. Allopurinol inhibits the enzyme xanthine oxidase to reduce urate synthesis, and Probenecid increases fractional excretion of uric acid.

Answer 155

Osteomalacia It results from incomplete mineralisation of bone in adults. It is common in the elderly with vitamin D deficiency being the most common cause. Rickets also results from defective bone mineralisation but occurs in children prior to growth plate closure. Osteoporosis is caused by a loss of bone mass rather than mineralisation, and therefore the biochemistry is normal. Osteoporosis is an age related process that particularly affects women post-menopause. Those with early menopause or who suffered from childhood illness are at increased risk. It is asymptomatic and usually presents first as a fracture, typically of the neck of femur, vertebra or wrist.

Answer 156

Pseudohypoparathyroidism The endocrinologist Fuller Albright was first to suggest pseudohypoparathyroidism results from an inherited resistance to PTH. He also identified the characteristic phenotypic appearance amongst these patients which includes short 4th and 5th metacarpals, obesity and rounded facies. This syndrome is now known as Albright hereditary osteodystrophy.

Answer 157

CATCH 22 (22q11.2), (with the 22 referring to the chromosomal deletion): Cardiac anomalies Abnormal facies Thymic aplasia Cleft palate Hypoparathyroidism ( Individuals with DiGeorge syndrome are born without the 3rd and 4th branchial arches and so do not have parathyroid glands.)

Answer 158

Salicylates Patients with Salicylate (Aspirin) poisoning typically experience nausea and vomiting, dizziness and ringing in the ears. Severe poisoning characteristically causes a respiratory alkalosis with metabolic acidosis. This is because salicylates stimulate the respiratory centre causing hyperventilation and inhibit the Krebs cycle resulting in anaerobic metabolism.

Answer 159

Type 3 hyperlipoproteinemia Human apolipoprotein E (ApoE) plays a crucial role in cholesterol and lipid metabolism. There are three major isoforms of ApoE: ApoE2, ApoE3, and ApoE4. ApoE3 is the most common isoform found in the majority of the population. ApoE4 is found with increased prevalence amongst those with Alzheimer’s disease and is thought to confer increased risk of the condition, whereas ApoE2 is thought to provide some protection against Alzheimer’s disease. ApoE2 is also the cause of Type 3 hyperlipoproteinemia (Familial dysbetalipoproteinaemia), a condition characterised by increased total cholesterol and triglycerides.

Answer 160

Negative effect Phosphoribosyl pyrophosphate amidotransferase (PAT) is the enzyme responsible for the conversion of PRPP into PRA. This is the rate limiting step in the de novo synthesis of purines. Guanylic acid (GMP) and adenylic acid (AMP) exert negative feedback on PAT.

Answer 161

NPC 1L1 NPC1L1 (Niemann-Pick C1-like 1) transporter is found on epithelial cells of the GI tract and hepatocytes and is involved in the absorption of cholesterol from the gut. Ezetimibe is a sterol absorption inhibitor which targets the NPC1L1 transporter. Ezetimibe results in lower blood cholesterol and can be prescribed alongside a statin.

Answer 162

Insulin overdose C-peptide is a short chain of amino acids cleaved in the conversion of proinsulin to insulin. It is created in equimolar amounts to insulin making it useful in the investigation of hypoglycaemia. Hypoglycaemia with high insulin and low C-peptide suggests an exogenous source of insulin. This may be in a type 1 diabetic or from surreptitious use of insulin. Hypoglycaemia with high insulin and high C-peptide suggests an endogenous source of insulin. Causes include insulinoma and inborn errors of metabolism. Sulfonylureas, used to lower blood sugar in type 2 diabetes, may also cause hypoglycaemia with high C-peptide due to increased release of endogenously produced insulin. Factitious hypoglycaemia may be caused by surreptitious use of insulin or sulfonylureas. A Sulfonylurea screen is useful in distinguishing an insulin-secreting tumour from surreptitious sulfonylurea ingestion.

Answer 163

1st metatarsophalangeal (MTP) Gout is a crystal arthropathy caused by the deposition of monosodium urate crystals in the synovium of joints. In chronic gout (tophaceous) there may also be deposition of crystals (tophi) around joints and at other locations such as the ear lobes. Acute gout (podagra) presents as a rapid build-up of severe pain in a red and swollen joint. The most common joint to be affected is the 1st metatarsophalangeal joint and it is more common in men. Monosodium urate crystals are negatively birefringent which means under polarised light they appear orange when parallel to a red light filter and blue when perpendicular. This allows them to be differentiated from calcium pyrophosphate crystals of pseudogout which show positive birefringence.

Answer 164

Cholesteryl ester transfer protein (CETP) Cholesteryl ester transfer protein (CETP) mediates the movement of cholesteryl ester from HDL into VLDL/LDL, and the movement of triglyceride from VLDL/LDL into HDL. A defect in this protein is a cause of hyperalphalipoproteinemia 1 (HALP1) where there are raised levels of HDL-cholesterol.

Answer 165

Lead Saturnine gout presents similarly to primary gout but with acute attacks more common in the knee. It is caused by lead toxicity, often associated with drinking homemade alcohol. Lead toxicity reduces renal urate excretion leading to hyperuricaemia.

Answer 166

Normal calcium levels Pseudopseudohypoparathyroidism presents with the phenotypic appearances of Albright hereditary osteodystrophy but with normal biochemical findings and without resistance to parathyroid hormone (PTH).

Answer 167

Orlistat Orlistat is a anti-obesity drug, which inhibits lipases from breaking down triglycerides into free fatty acids which can then be absorbed from the gut. A side effect of this is steatorrhoea and patients are advised to follow a low-fat diet to reduce this side effect.

Answer 168

Tangier disease Tangier disease is an inherited disorder caused by mutations in the ABCA1 gene (HDL deficiency). This prevents the release of cholesterol and lipids from cells which results in them accumulating in certain organs. This may present as hepatomegaly, splenomegaly, or classically as enlarged orange tonsils in children. The condition is characterised by low HDL levels in the blood conferring an increased risk of cardiovascular disease.

Answer 169

Allopurinol and azathioprine should not be co-prescribed unless the combination cannot be avoided. Allopurinol interferes with the metabolism of azathioprine, increasing plasma levels of 6-mercaptopurine which may result in potentially fatal blood dyscrasias.

Answer 170

a rise in serum ALP and GGT in ALD patients compared to NASH patients.

Answer 171

Paracetamol is a regularly prescribed analgesic and antipyretic due to its low side-effect profile; however it can result in accumulation of 5-oxoproline in individuals who are predisposed to reduced glutathione levels, leading to high anion gap metabolic acidosis.

Answer 172

If you just have fat but no damage to your liver, the disease is called nonalcoholic fatty liver disease (NAFLD). If you have fat in your liver plus signs of inflammation and liver cell damage, the disease is called nonalcoholic steatohepatitis (NASH).

Answer 173

Alcoholic fatty liver disease in UK (1/3rd of liver disease deaths) -Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide,

Answer 174

Cushing disease occurs when Cushing syndrome is caused by an ACTH-producing pituitary tumor, whereas Cushing syndrome is the set of symptoms that results when there is a surplus of cortisol in the body -the standard high-dose dexamethasone suppression test has been reported to be 86 percent accurate in differentiating Cushing's disease from ectopic ACTH production.

Answer 175

Bitemporal hemianopsia most commonly occurs as a result of tumors located at the mid-optic chiasm. Since the adjacent structure is the pituitary gland, some common tumors causing compression are pituitary adenomas and craniopharyngiomas. Also, another relatively common neoplastic cause is meningiomas.

Chem Path (Meded) Flashcards

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