Chem Path (Meded) Flashcards
what is the value range for normal osmolality?
275 – 295 mOsmol/kg
What’s the difference between osmolarity & osmolality?
Osmolality=mOsm/kg of solvent (more accurate, measured by automated lab machine) ;It does not vary with temperature as it is measured per 1 Kilogram of solvent, and is therefore the preferred term for biological systems.
OsmolaRity=mOsm/litRe of solvent (more practical, calculated from blood tests)
How to calculate osmolality?
Osmolality: (2x Na + K) + glucose + urea
What’s the biggest contributor to osmolality?
sodium
Rank the expected calculated osmolality in patients with each of the following outcomes, with 1 being the highest osmolality and 5 being the lowest.
Diabetes insipidus
Diabetic ketoacidosis
Hyperosmolar hyperglycaemic state
Pneumonia
SIADH
- Hyperosmolar hyperglycaemic state
- Diabetic ketoacidosis
- Diabetes insipidus
- Pneumonia
- SIADH
What is the definition of hyponatraemia?
Sodium concentration < 135 mmol/L
What is the underlying pathogenesis of hyponatraemia?
Increased extracellular water (relative excess water)
What are the 2 main stimuli of ADH release?
- Increased serum osmolality (via hypothalamic osmoreceptors)
- Blood volume/pressure (via baroreceptors)
What is the first step in the management of hyponatraemia?
Assess their volume status
What causes normal osmolality in pseudohyponatraemia?
lipids, proteins
What causes high osmolality in pseudohyponatraemia?
alcohol, sugars
what are some clinical features of hypovolaemia?
Tachycardia
Postural hypotension
Dry mucous membranes
Reduced skin turgor
Confusion
Reduced urine output
What is the most reliable clinical sign of hypovolaemia?
Low urine sodium (suggests that you are trying to retain fluid)
NOTE: this may be high in patients on diuretics
what are some clinical signs of hypervolaemia?
Raised JVP
Bibasal crackles
Peripheral oedema
How is hypovolaemic hyponatraemia managed?
- treat underlying cause
- IV 0.9% NaCl
- slow IV hypertonic 3% NaCl
List some causes of hypovolaemic hyponatraemia (urinary sodium<20 and >20mmol/L)
<20mmol/L (extra-renal):
1. vomiting
2. diarrhoea
3. burns
> 20mmol/L (renal)
1. renal disease
2. diuretics
3. salt wasting nephropathy
how is euvolaemic hyponatraemia treated?
- treat underlying cause
- fluid restrict
- demeclocycline or tolvaptan for resistant SIADH
List some causes of euvolaemic hyponatraemia:
If < 20 mmol/L = psychogenic polydipsia, tea and toast diet
If > 20 mmol/L = hypothyroidism, adrenal insufficiency, SIADH
what are the 3 steps of assessing hyponatraemia
- True/false (osmolality low in true hyponatraemia)
- Check volume status (for hypo/eu/hypervolaemia)
- Is urinary sodium >20mmol/L (renal cause) or <20mmol/L (extra-renal cause)
List some causes of hypervolaemic hyponatraemia:
If < 20 mmol/L =”failures”: CCF, cirrhosis, nephrotic syndrome
If > 20 mmol/L = CKD
what is the management of hypervolaemic hyponatraemia?
treat underlying cause, fluid restrict (because hypervolaemic)
what is anion gap and value?
=cations - anions=
(Na + K)- (HCO3 + Cl),
14-18mmol/L
what are causes of raised anion gap? (mnemonic)
how is SIADH diagnosed (mnemonic):
-Low plasma sodium (< 135)
-Low plasma osmolality (< 270)
-High urinary sodium (> 20)
-High urinary osmolality (> 100)
-No adrenal/thyroid/renal dysfunction (early morning cortisol and TFTs)
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
- Brain pathology is a known cause of SIADH (brain, lungs, pills)
how can clinical features of hypocalcaemia be remembered (mnemonic):
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
what are some causes of hypocalcaemia?
- Vitamin D deficiency
-Malnutrition (i.e. osteomalacia)
-Malabsorption (e.g. gastrectomy, short bowel syndrome, Coeliac disease, chronic pancreatitis)
-CKD - Hypoparathyroidism
-Post-parathyroidectomy, postradiation, autoimmune
-Inherited (eg iron deposition in people with thalassaemia)
-hypo/hypermagnasaemia
-Pseudohypoparathyroidism (resistance to PTH)
-DiGeorge syndrome - Hyperphosphataemia
-Tumour lysis syndrome
-Rhabdomyolysis
-Phosphate administration - Acute pancreatitis (sequestration of serum calcium to proteins released dying pancreatic tissue)
5.Hypomagnesaemia - Acute alkalosis
If potassium is low, what should you also check?
magnesium
A 62-year-old lady with no past medical history presents with non-specific symptoms of mild nausea and fatigue. The GP does a full workup and eventually diagnoses her with chronic kidney disease and hypocalcaemia. Her magnesium levels are noted to be normal. Apart from referring her to secondary care, the GP also prescribes her with calcium carbonate tablets and one additional supplement.
Which of the following is the most likely additional supplement to have been prescribed?
A. ergocalciferol
B. calcefediol
C. Cholecalcifriol
D. Calcitriol
E. 7-dehydrocholesterol
Answer: Calcitriol (active form of vitamin D). In patients with CKD, final activation (hence vitamin D supplements must be in the active form)
An 84 year old man is admitted with a community acquired pneumonia. His past medical history includes hypertension, ischaemic heart disease and benign prostatic hyperplasia. His medications include tamsulosin, ramipril and bisoprolol. On examination he has coarse crepitations in the left lung base. He is normotensive and normocardic and is clinically euvolaemic. Laboratory tests return as follows:
Na+ 120 mmol/L (135-145) K+ 3.9 mmol/L (3.5-5) Ur 3.5 mmol/L (2.5-6.7) Cr 88 mmol/L (70-150) TSH 0.99 mU/L (0.5-5.7) Cortisol 840 nmol/L (140-520) Serum osmolality 268 mOsm/kg (275–295) Urine osmolality 587 mOsm/kg Urine sodium 43mmol/L (<20)
What is the most appropriate management of this patient’s hyponatraemia?
A. levothyroxine
B.IV hypertonic saline
C. IV normal saline
D. Iv hydrocortisone
E. Fluid restriction
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.
An 84 year old man is admitted with a community acquired pneumonia. His past medical history includes hypertension, ischaemic heart disease and benign prostatic hyperplasia. His medications include tamsulosin, ramipril and bisoprolol. On examination he has coarse crepitations in the left lung base. He is normotensive and normocardic and is clinically euvolaemic. Laboratory tests return as follows:
Na+ 120 mmol/L (135-145) K+ 3.9 mmol/L (3.5-5) Ur 3.5 mmol/L (2.5-6.7) Cr 88 mmol/L (70-150) TSH 0.99 mU/L (0.5-5.7) Cortisol 840 nmol/L (140-520) Serum osmolality 268 mOsm/kg (275–295) Urine osmolality 587 mOsm/kg Urine sodium 43mmol/L (<20)
What is the most appropriate management of this patient’s hyponatraemia?
A. levothyroxine
B.IV hypertonic saline
C. IV normal saline
D. Iv hydrocortisone
E. Fluid restriction
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.
An 83 year old man is admitted with confusion and vomiting. His past medical history includes hypertension and IBS. His medications include loperamide and ramipril. On examination he is euvolaemic and there are no specific clinical findings. Bloods are sent which return as follows:
Na 120 mmol/L (135-145) K 4.5 mmol/L (3.5-5) Ur 2.7 mmol/L (2.5-6.7) Cr 83 mmol/L (70-150)
What further investigations are necessary to confirm the likely diagnosis?
A. Serum ADH, paired serum and urine osmolalities and urine sodium
B. TSH, cortisol, paired serum and urine osmolalities and urine sodium
C. Paired serum and urine osmolalities and urine sodium
D. Serum ADH, TSH, cortisol, paired serum and urine osmolalities and urine sodium
E. Paired serum and urine osmolalities, urine sodium and potassium
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
A 71 year old patients is brought into the emergency department after two cycles of cardiopulmonary resuscitation. The paramedics hand over that he required two shocks due to ventricular fibrillation. After reviewing his initial blood gas, treatment of insulin, dextrose and calcium gluconate is commenced.
Which of the following is most likely to have caused cardiac arrest in this patient?
A. Bendroflumethiazide therapy
B. Conn’s syndrome
C. Steroid therapy
D. Rhabdomyolysis
E. Liquorice abuse
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
A 68 year old female patient is admitted to the emergency department with a five day history of a campylobacter positive diarrhoeal illness. She is clinically dehydrated on admission and has suffered with a poor oral intake for the last five days. She takes no regular medications.
Her observations are as follows:
19 breaths/min
97% room air
99/64 mmHg
96 bpm
Afebrile
On examination she is clinically dehydrated with dry mucous membranes and a clear chest bilaterally with normal heart sounds and a tender abdomen in the epigastrium and hyperactive bowel sounds.
Her blood tests have been sent and are awaited
Her ECG is seen below:
A. Hypercalcaemia
B. Hypomagnasaemia
C. Hypokalaemia
D. Hyperkalaemia
E. Hypothermia
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
A 72-year-old gentleman, with known chronic kidney disease, was referred to A&E for hyperkalaemia discovered incidentally on a blood test ordered by his GP. He is asymptomatic. In the referral letter, the potassium result was noted to be 5.8 mmol/L, which was confirmed by a venous blood gas sample in the resuscitation area. An ECG performed revealed a normal sinus rhythm.
Which of the following options is the single best management for this patient?
A. Haemodialysis
B. Intravenous calcium gluconate
C. Intravenous insulin-glucose solution
D. Oral calcium resonate
E. Nebulised salbultamol
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
A 72-year-old gentleman, with known chronic kidney disease, was referred to A&E for hyperkalaemia discovered incidentally on a blood test ordered by his GP. He is asymptomatic. In the referral letter, the potassium result was noted to be 5.8 mmol/L, which was confirmed by a venous blood gas sample in the resuscitation area. An ECG performed revealed a normal sinus rhythm.
Which of the following options is the single best management for this patient?
A. Haemodialysis
B. Intravenous calcium gluconate
C. Intravenous insulin-glucose solution
D. Oral calcium resonate
E. Nebulised salbultamol
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
What are 2 main investigations for hypokalaemia?
- Serum magnesium – correct if low (Adequate magnesium intake is required for maintaining normal potassium levels, because hypomagnesaemia results in excess urinary excretion of potassium)
- Aldosterone:renin ratio (if concomitant high BP); Primary hyperaldosteronism (Conn’s) presents with hypertension and hypokalaemia.
What electrolyte abnormality is associated with digoxin toxicity?
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
A 72 year old lady has been feeling unwell for several years with the clinical manifestations of primary hyperparathyroidism including renal stones, osteopenia and low mood.
She has neck imaging which confirms a solitary parathyroid adenoma and she is listed for a parathyroidectomy.
What is the commonest complication of this procedure (electrolyte abnormality)?
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
A T score of what on DEXA confirms osteoporosis?
<2.5
A 75-year-old female presents to her GP accompanied by her Daughter. The patient has had suffered 2 falls at home within the last month, both without significant injury. The patient has never had a fracture in the past, but her daughter understands that older people have “weak bones” and that if her mother continues to fall, she could end up with a hip fracture. She has read on the internet that bones can be strengthened with bisphosphonates, and requests some for her mother. What is the best initial step in deciding whether this patient should be offered bisphosphonates?
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
A 75-year-old female presents to her GP accompanied by her Daughter. The patient has had suffered 2 falls at home within the last month, both without significant injury. The patient has never had a fracture in the past, but her daughter understands that older people have “weak bones” and that if her mother continues to fall, she could end up with a hip fracture. She has read on the internet that bones can be strengthened with bisphosphonates, and requests some for her mother. What is the best initial step in deciding whether this patient should be offered bisphosphonates?
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
what electrolyte disturbances does tumour lysis syndrome cause?
hypocalcaemia, hyperphosphataemia, hyperkalaemia , hyperuricaemia
what does AST: ALT >2:1 indicate?
alcoholic hepatitis
what does Raised AST:ALT < 1:1 indicate?
viral hepatitis
What does ALP > ALT indicate?
- Biliary obstruction
what does Ast: Alt>1 indicate?
advanced fibrosis or cirrhosis
What does ALT/AST in the 1000s indicate?
toxins eg paracetamol, ischaemia eg ischaemic shock, viral hepatitis
what are markers of liver function?
Clotting – PT/INR
Albumin
Bilirubin
what are markers of liver damage?
Bilirubin
ALT, AST
GGT
ALP
what is the half life of albumin
20 days
what is caeruloplasmin used to test (if <50yr)
Wilson’s disease. worry if it’s low
what hepatitis blood tests do you do for liver panel?
Hep B surface antigen, Hep C antibody
what is rhodamine dye used to diagnose?
Wilson’s disease
what are some causes of an isolated rise in bilirubin include:
- Gilbert’s syndrome: the most common cause.
- Haemolysis: check a blood film, full blood count, reticulocyte count, haptoglobin and LDH levels to confirm.
how to tell if deranged lfts are acute/chronic?
if albumin function not preserved–> chronic
what is ALT a marker of?
hepatocellular injury
what is ALP a marker of?
marker of cholestasis
3 things that put ALT over 1000:
Toxins, viruses (acute viral hepatitis) and ischaemia
what can augmentin cause?
cholestatic picture
Causes of an isolated rise in ALP include:
-Bony metastases or primary bone tumours (e.g. sarcoma)
-Vitamin D deficiency
-Recent bone fractures
-Renal osteodystrophy
Name the common blood test that best indicates acute liver dysfunction?
INR
Give an example of biguanide:
metformin
Give an example of sulfonylurea:
gliclazide
Give an example of a-glucosidase inhibitor:
acarbose
Give an example of DDP-4 inhibitor:
saxagliptin citagliptin, linagliptin, vildagliptine
Give an example of GLP1 receptor agonist:
exenatide, liraglutide lixisenatide
Give an example of SGLT2 inhibitor:
dapagliflozin, empagliflozin, canagliflozin
Give an example of insulins:
glargine, detemir
what does Slightly elevated ALT mean?
fatty liver
What further imaging is indicated for a confirmed transient ischaemic attack of the anterior circulation when neurological symptoms have resolved?
Carotid Ultrasound
Which histological subtype of malignancy are patients with poorly controlled ulcerative colitis at increased risk for?
adenocarcinoma
which cancer is associated with coeliac disease?
Enteropathy associated T-cell lymphoma (EATL) is a T-cell lymphoma
which enzyme goes up in viral hepatitis?
ALT (more than AST)
what causes Measured osmolality – calculated osmolality > 10mOsmol/kg
Alcohol: methanol, ethanol
Sugars: mannitol, sorbitol
Lipids: hypertriglyceridaemia
Proteins: hypergammaglobulinaemia
What 5 tests should you do to diagnose diabetes insipidus?
- Serum glucose – to exclude DM
- Serum potassium – to exclude hypokalaemia
- Serum calcium – to exclude hypercalcaemia
- Plasma and urine osmolality
- Water deprivation test (diagnosis of exclusion)
what is the diagnostic criteria of DI?
despite raised plasma osmolality, urine is dilute with a urine:plasma osmolality of < 2:1
A 65 year old gentleman who is a long-term smoker presented with a 2-month history of cough, shortness of breath and weight loss.
His examination is unremarkable.
His investigation results are as follows: Na 128, K 4.0, adjusted Ca 2.4, urinary sodium 40, normal TSH and cortisol level.
His CXR report is pending.
What is the next best step in investigation?
Paired serum and urine osmolalities
what are key features of hypokalaemia? (mnemonic)
muscle weakness, cramps, hypotonia
what are ecg features of hypokalaemia:
flattened/inverted T wave, prominent U wave, prolonged PR interval, ST depression
what are causes of hypokalaemia?
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
if there is acidosis with hypokalaemia, what could be the cause?
consider renal tubular acidosis (type 1 and 2), partially treated DKA
how to manage mild to moderate hypokalaemia (2.5-3.5mmol/L)
oral Sando-K
how to manage severe hypokalaemia <2.5mmol/L
10 mmol/hour IV KCl, continuous ECG monitoring
ecg changes in hyperkalaemia:
tall tented T wave, small P wave, widened QRS, prolonged PR interval, sine wave
hyperkalaemia causes: (mnemonic)
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
what’s the treatment for hyperkalaemia
- recheck K+ levels if >6.5mmol/l (haemolysis)
- 10mls 10% calcium gluconate (cardioprotective)
- 100mls 20% dextrose (stimulates insulin release) and 10 units short-acting insulin eg actrapid
- nebulised salbutamol
- in some cases consider calcium resonium 15g or 30g PR (binds potassium in gut)
how to differentiate between 1 and 3 hyperparathyroidism?
primary: suspect Men1 /2a syndrome
tertiary: late stage CKD (autologous vitamin D)
what are some signs/symptoms of hypocalcaemia? (mnemonic)
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.
what are some causes of hypocalcaemia?
Hypoparathyroidism – DiGeorge (primary), post-thyroidectomy (secondary), low magnesium
Vitamin D deficiency
what are some investigations of hypocalcaemia?
ECG (bedside), bloods (Mg, phosphate, PTH level, ALP), imaging (consider DEXA if # history)
management of hypocalcaemia (mild/severe)?
-Mild (> 1.9 mmol/L, no Sx) – Oral calcium, vitamin D supplement
-Severe (< 1.9 mmol/L, Sx present) – IV calcium gluconate
what are some causes of hypercalcaemia with low PTH?
Low PTH – malignancy (PTHrP, bony mets, multiple myeloma), hyperthyroidism, hypoadrenalism, sarcoidosis, thiazides, vitamin D excess
what are some causes of hypercalcaemia with high PTH:
Raised PTH – primary and tertiary hyperparathyroidism
How to differentiate – late-stage CKD in tertiary
Suspect MEN1 and 2a syndrome if primary
Rank the plasma calcium concentration in the following conditions, with 1 bring the lowest and 5 being the highest.
Primary hyperparathyroidism
Secondary hyperparathyroidism
Osteoporosis
Osteomalacia
Parathyroid carcinoma
- Osteomalacia
- Secondary hyperparathyroidism
- Osteoporosis
- Primary hyperparathyroidism
- Parathyroid carcinoma
Osteomalacia – Vitamin D very low need for calcium absorption, calcium will fall themost
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)
investigations for hypercalcaemia:
myeloma screen, TFTs (hyperthyroidism can cause bone resorption), cortisol level (to rule out Addison’s)
what is the management of hypercalcaemia?
Acute: IV 0.9% NaCl +/- diuretics
Medical: Bisphosphonates (malignant hypercalcaemia), cinacalcet
Surgical: Parathyroidectomy if parathyroid adenoma
What is the most common cause of hypocalcaemia in the community?
vitamin D deficiency
what is the commonest cause of hypercalcaemia in the community?
parathyroid adenoma
what is the commonest cause of hypercalcaemia in hospital?
malignancy
what are the causes of secondary hyperparathyoidism?
The most common causes of secondary hyperparathyroidism are kidney failure and vitamin D deficiency.
causes of raised anion gap (mnemonic)
MUDPILES
causes of prehepatic jaundice
Prehepatic – haemolytic anaemia, ineffective erythropoiesis
Key – absent conjugated bilirubin, absent urine bilirubin
causes of hepatic jaundice
Hepatic – hepatocellular dysfunction, impaired conjugation, impaired bilirubin uptake
causes of posthepatic jaundice
Post-hepatic (obstruction) – stones, pancreatic cancer
Key – dark urine (raised urobilinogen), pale stool (low stercobilinogen
causes of raised unconjugated bilirubin:
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)
causes of raised conjugated bilirubin:
Hepatocellular dysfunction – congenital, infections, toxins, autoimmune, neoplasm, vascular
Decreased hepatic excretion – congenital (Dubin-Johnson, Rotor syndrome)
what is the best marker of liver function in acute liver injury?
Prothrombin time
which enzymes are raised in acute myocardial infarction
troponin
creatine kinase (MB)
AST
LDH
why are cortisol levels checked in hypercalcaemia?
Men2 syndrome
what are the different MEN syndromes? (mnemonic) & mode of inheritance
-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)
inheritance pattern in MEN syndromes;
autosomal dominant
how does adrenaline affect K+ levels
adrenaline causes hypokalaemia
An 88 year old man is admitted with confusion and pleuritic chest pain beginning 2 days ago. His wife reports extremely poor oral intake over the preceding week and states that he has not passed urine for 2 days. His background include poorly controlled diabetes, hypertension and COPD. On examination he is GCS 14/15 and has bibasal crepitations. Examination is otherwise unremarkable. An ABG is performed which demonstrates the following:
pH 7.29 (7.35-7.45) pO2 13.7 kPa on room air (>10.6) pCO2 2.6 kPa (4.7-6) HCO3- 12 mmol/L (22-28) Lactate 1.7 mmol/L (0.6-1.8) Na+ 141 mmol/L (135-145) K+ 4.9 mmol/L (3.5-5) Cl- 104 mmol/L (95-105)
What is the most likely cause of this presentation?
A. Myocardial infarction
B. Pulmonary embolus
C. Acute kidney injury
D. Acute exacerbation of COPD
E. Hyperosmolar Hyperglycaemic State
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
An 88 year old man is admitted with confusion and pleuritic chest pain beginning 2 days ago. His wife reports extremely poor oral intake over the preceding week and states that he has not passed urine for 2 days. His background include poorly controlled diabetes, hypertension and COPD. On examination he is GCS 14/15 and has bibasal crepitations. Examination is otherwise unremarkable. An ABG is performed which demonstrates the following:
pH 7.29 (7.35-7.45) pO2 13.7 kPa on room air (>10.6) pCO2 2.6 kPa (4.7-6) HCO3- 12 mmol/L (22-28) Lactate 1.7 mmol/L (0.6-1.8) Na+ 141 mmol/L (135-145) K+ 4.9 mmol/L (3.5-5) Cl- 104 mmol/L (95-105)
What is the most likely cause of this presentation?
A. Myocardial infarction
B. Pulmonary embolus
C. Acute kidney injury
D. Acute exacerbation of COPD
E. Hyperosmolar Hyperglycaemic State
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
A 53 year old female presents to hospital with a one day history of colicky abdominal pain, painful spasms and perioral paraesthesia. Last week she completed a course of radio-iodine for Grave’s disease. She has no other medical history of note other than Vitamin D deficiency. She takes no medication.
On examination she is Trousseau’s and Chvostek’s sign positive. An ECG is done which is normal. Bloods tests are done which show the following:
Corrected calcium 1.73 mmol/L (2.12-2.65) Phosphate 4.83 mmol/L (2.5-4.5) PTH 0.01 pmol/L (0.8-8.5) ALP 83 mmol/L (30-150)
What is the most appropriate immediate treatment for this patient?
A. Oral calcium supplements
B. IV Furosemide
C. Encourage increased oral calcium and Vitamin D intake
D. IV calcium gluconate
E. Oral Vitamin D supplements
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
An 83 year old female is seen on the care of the elderly ward round. She has now been admitted for 3 days for treatment of an exacerbation of heart failure. The nurses have expressed concerns about her eating and she is currently awaiting a dietician review.
Blood tests this morning reveal an isolated hypokalaemia with a serum potassium 2.6mmol/L (3.5-5.5). An ECG is done which shows ST depression and U-waves.
What is the most appropriate management of this patient?
A. 4 hour IV infusion of 1L 0.9% saline containing 40mmol potassium chloride
B. 40mmol potassium chloride IV bolus
C. Stop furosemide, no treatment required
D. Oral slow release potassium chloride
E. 4 hour IV infusion of 1L 5% dextrose containing 40mmol potassium chloride
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
An 84-year-old woman is brought to the emergency department with lethargy and confusion. Her son reports that she has been excessively thirsty recently, and has lost a considerable amount of weight in the past few months. She has been struggling to do her daily activities due to dyspnoea. Severe right-sided hip pain in the last few months has also been a source of distress. She has a past medical history of Type 2 diabetes controlled by Metformin, and is an ex-smoker with a 30 pack-year history.
Her observations are below:
Observations
HR 125
BP 79/50
RR 14
SaO2 97%
T 37.6
Blood results are below:
Blood results Normal values
Hb: 130 (female 115-165 g/L)
MCV: 80 (76-96 fL)
WCC: 5.7 (4.0-11.0 × 109/L)
Platelets: 310 (150-400 × 109/L)
ESR: 20 (women over 50: <30mm/h)
Fasting glucose: 9mmol/L (4-7mmol/L)
HbA1C: 50 mmol/mol (<48 mmol/mol)
Corrected Calcium: 3.1 (2.2-2.6 mmol/L)
ALP: 300 (30-130U/L)
PTH: 2.0 (1.05 - 6.83 pmol/L)
Phosphate: 2 (0.8-1.5mmol/L)
What is the single most likely underlying cause of her symptoms?
A. Diabetes Mellitus
B. Sarcoidosis
C. Bone Metastases
D. Primary hyperparathyroidism
E. Multiple Myeloma
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
An 83 year old lady is admitted with severe diarrhoea and vomiting. Her bloods show a serum potassium of 2.8 mmol/L. Her ECG is normal sinus rhythm. What is the most appropriate management of these patients?
A. 1L normal saline with 40mmol potassium chloride given over 12 hours
B. 1L normal saline with 40mmol potassium chloride given over 4 hours
C. 1L normal saline with 80mmol potassium chloride given over 4 hours
D. Oral Sando K for 3 days
E. 40mmol potassium chloride given over 15min
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
A 68 year old female is seen in AMU. She has a 2 week history of pins and needles in her hands and feet after a subtotal thyroidectomy for Grave’s disease.
Her ECG is shown below:
A. Calcium
B. Sodium
C. Phosphate
D. Potassium
E. Magnesium
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
A 31 year old lady is admitted with significant abdominal pain, vomiting and a seizure following recently starting a course of trimethoprim for a UTI. She is noted to be tachycardic and hypertensive. Her urine is noted to be dark red and her urinary porphobilinogen levels are raised. What is the most appropriate management of this patient?
A. IV ceftriaxone
B. Blood transfusion
C. IV haematin
D. Laparotomy
E. Low carbohydrate diet
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
A 46 year old woman has frequent flare ups of her rheumatoid arthritis. Her management is escalated to biological agents. Her rheumatologist would like to monitor disease progression closely.
Which inflammatory marker is most useful to monitor disease progression?
A. C-reactive protein (CRP)
B. Anticyclic citrullinated peptide antibodies (anti-CCP)
C. Albumin
D. Erythrocyte sedimentation rate (ESR)
E. Fibrinogen
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
A 56-year-old gentleman, with no past medical history, presents to his GP with polyuria. He is not on any diuretic nor high-protein diet, his blood glucose level is within normal limits. Further workup suggests he passes 4.5L of urine a day, plasma osmolality is 295 mOsmo/kg, urinary osmolality is 50 mOsmo/kg and serum sodium is raised at 147 mmol/L. On giving desmopressin, the plasma osmolality and urine output markedly decrease, while the urine osmolality increases to 700 mOsmo/kg.
Which of the following is the single most likely diagnosis?
A. Psychogenic polydipsia
B. Central diabetes insipidus
C. Syndrome of inappropriate anti-diuretic hormone
D. Diabetes mellitus
E. Nephrogenic diabetes insipidus
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)
what does
Urine concentrates after restriction mean
normal or primary polydipsia
what does Urine concentrates after desmopressin mean:
central DI
what does Urine remains dilute after desmopressin mean:
nephrogenic DI
A 65 year old gentleman who is a long-term smoker presented with a 2-month history of cough, shortness of breath and weight loss.
His examination is unremarkable.
His investigation results are as follows: Na 128, K 4.0, adjusted Ca 2.4, urinary sodium 40, normal TSH and cortisol level.
His CXR report is pending.
What is the next best step in investigation?
Paired serum and urine osmolalities
An 80 year old man is being looked after by the orthopaedic team following a recent fall and a fractured neck of femur. He undergoes bilateral hip and femoral X-rays to compare both hip joints and limbs. The X-rays show changes consistent with Paget’s disease. Of the following, which of the following is the most common presenting feature in patients with Paget’s disease?
A. Bowed legs
B. Asymptomatic
C. Osteosarcoma
D. Pain
E. Fractures
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
what electrolyte disturbance is most common in patients with renal failure?
hyperkalaemia as the kidneys would usually maintain potassium homeostasis by excreting any excess.
A 49 year old man has severe asthma requiring multiple courses of prednisolone in the last year. His 10 year FRAX risk of sustaining a hip fracture is calculated as 15%. His DEXA scan results are as follows: T-score at femoral neck: -2.9, T-score in spine: -2.4, Z-score at femoral neck: -1.4, Z-score in spine: -1.1.
What is the next best step for this patient?
A. Treat for osteoporosis
B. Advise the patient his hip is less likely to fracture compared with the average population
C. Advise the patient he will definitely suffer a hip fracture if he is not treated
D. Warn the patient he has osteopenia, and monitor every 6 months
E. Improve asthma control and repeat FRAX score in 12 months
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
A 21 year old male is admitted with nausea, vomiting, diarrhoea and generalised abdominal pain which started 2 days ago.
On examination, he has dry mucous membranes, a thready pulse and a non-visible JVP. Examination is otherwise unremarkable and the patient is oriented to time, place and person.
An arterial blood gas (ABG) is performed which demonstrates the following:
pH 7.31 (7.35-7.45) pO2 13.3 kPa on room air (>10.6) pCO2 2.4 kPa (4.7-6) HCO3- 16 mmol/L (22-28) Lactate 1.1 mmol/L (0.6-1.8)
A set of bloods are done and return as follows:
Na+ 140 mmol/L (135-145) K+ 4.3 mmol/L (3.5-5) Cl- 104 mmol/L (95-105) Ur 8.1 mmol/L (2.5-6.7) Cr 171 mmol/L (70-150)
What is the most likely cause of this patient’s presentation?
A. Uraemia
B. Diarrhoea
C. Lactic acidosis
D. Diabetic ketoacidosis
E. Renal tubular acidosis Type 1
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
what is the management of Paget’s disease
- Analgesia
- Bisphosphonates (eg. alendronic acid, pamidronic acid) - inhibit osteoclast activity
- Typically treatment lasts 6 months and following completion bone activity may return to normal
- Monitor at regular 6 or 12 month intervals for recurrence
SIADH causes (mnemonic)
brain, lung, pills, malignancy (eg small cell lung cancer:ACTH, ADH)
value for prolonged QTc interval: (+ ECG small square/large square)
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
Causes of prolonged QTc interval:
electrolytes: hypomagnesiumia, hypokalaemia, hypothermia
A 76-year-old gentleman with long-standing chronic kidney disease presents with bone pain, constipation, abdominal pain and muscle weakness. The renal physician looking after him suspects he has developed tertiary hyperparathyroidism. He orders some blood tests including a bone profile and parathyroid hormone levels to confirm this.
Which of the following investigation results is most likely to be seen in tertiary hyperparathyroidism?
A. Normal parathyroid levels
B. Raised alkaline phosphatase levels
C. Low calcium levels
D. Creatinine at baseline levels
E. Reduced phosphate levels
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
Primary hyperparathyroidism causes:
-80% single parathyroid adenoma
-15% parathyroid hyperplasia/multiple parathyroid adenomas
-0.5% carcinomas (most carcinomas non-functional)
-Men1 (adenoma) and 2 (hyperplasia)
Primary hyperparathyroidism Ca, phosphate, vit D, ALP, PTH:
-Ca: high
-phosphate: low (PTH causes phosphate excretion from kidneys)
-vitamin D: normal
-ALP: normal/high
-PTH: high/normal
Secondary hyperparathyroidism causes:
-CKD
-osteomalacia (long term), vitamin D deficiency
-malabsorption syndromes
Secondary hyperparathyroidism Ca, phosphate, vit D, ALP, PTH:
-Ca: low
-vitamin D: normal/low (CKD; less active vitamin D/vitamin D deficiency)
-phosphate: high
-ALP: high
-PTH: high
Tertiary hyperparathyroidism causes:
-prolonged secondary hyperparathyroidism (causing unregulated secretion of PTH)
-kidney transplant
Tertiary hyperparathyroidism Ca, phosphate, vit D, ALP, PTH:
-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)
hypoparathyroidism causes
causes of hypercalcaemia (mnemonic):
Chimpanzee
management of tumour lysis syndrome
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.
what is tumour lysis syndrome?
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.
symptoms of tumour lysis syndrome
include nausea, vomiting and muscle pain
Important investigations for tumour lysis syndrome:
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).
A 94 year old man is admitted with suprapubic pain, fevers and urinary retention. His past medical history includes dementia, hypertension and diabetes. On examination he is peripherally flushed, pyrexial, tachycardic, hypotensive with suprapubic tenderness. Examination is otherwise unremarkable. His ECG and chest x-ray is normal. His urine dip is positive for nitrites and blood. Bloods show CRP 201 (<5), WCC 19.2 (5-11), Troponin 321 nmol/L (<20) and Repeat troponin 318 nmol/L (<20). What is the most appropriate management of this patient?
A. Aspirin, clopidogrel and treatment dose low molecular weight heparin
B. IV antibiotics and fluids
C. Oral antibiotics and fluid restriction
D. Thrombolysis
E. Immediate primary percutaneous coronary intervention
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
A 45-year-old male is investigated for polyuria. A water deprivation test is done to ascertain the cause.
Water deprivation started at 8 am.
Plasma osmolality after 8 hours 305 mOsm/kg
Urine osmolality after 8 hours 190 mOsm/kg
Urine osmolality after 4 hours after desmopressin 575 mOsm/kg
Based on the presumed diagnosis, what feature is this patient most likely to have in their past medical history?
A.A recent acute kidney injury (AKI)
B. Concurrent lithium use
C. Primary hyperparathyroidism
D. Recent transsphenoidal pituitary surgery
E. Schizophrenia
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.
Causes of normal anion gap:
- 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) - Increased production of H+, such as;
-Toluene (crude oil/mining) poisoning
-Lysine or arginine administration (found in total parental nutrition) - Decreased excretion of H+, such as;
-Renal tubular acidosis types 1 and 4
A 73-year-old woman comes in with complaints of dizziness and generalised weakness over the last two weeks. Her family feel that she has been a little bit more confused than usual. Observations are all normal. Her only laboratory abnormality is a sodium of 124. She appears dehydrated.
Which one of the following medications is the most likely cause of her symptoms?
A. Bendroflumethiazide
B. Bisoprolol
C. High dose aspirin
D. Acetazolamide
E. Spironolactone
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
Hypovolaemia investigations:
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):
- Urea and Electrolytes (while not on diuretics) - to confirm hyponatraemia and to exclude mixed electrolyte abnormalities (not seen in SIADH)
- Urine and plasma paired osmolalities (while not on diuretics) - to demonstrate the inappropriate concentration of the urine
- Urine sodium (while not on diuretics) - to demonstrate sodium wasting in the kidneys
- Urine dip - to screen for infection and glomerular pathology
- TSH and cortisol - to exclude hypothyroidism (rare cause of euvolaemic hyponatraemia) and Addison’s disease
Hyperaldosteronism causes:
- Adrenal adenoma (Conn’s Syndrome)
- Bilateral adrenal hyperplasia
- Familial hyperaldosteronism
- Adrenal carcinoma
biochemical features of hyperaldosteronism:
- Hypertension
- Hypokalaemia
- Metabolic alkalosis
Clinical features/investigations for hyperaldosteronism:
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)
Management of hyperaldosteronism:
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).
A 82-year-old man is recovering from an episode of acute pulmonary oedema on the cardiology ward. He has a background of congestive heart failure and hypertension. His current list of medications includes Bisoprolol, Metolazone, Ramipril, Nifedipine, Spironolactone and Bumetanide. On the ward round today, the patient has an irregular pulse, but is otherwise relatively well. An electrocardiogram is performed which shows the following:
Which of his medications is most likely responsible for these changes?
A. Ramipril
B. Spironolactone
C. Bumetanide
D. Metolazone
E. Nifedipine
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
tourniquets and calcium levels:
they can elevate the calcium levels in the samples (can also cause pseudohyperkalaemia)
A 27 year old otherwise fit an well man is admitted for an open reduction and internal fixation of his left ankle. An initial set of bloods finds a serum potassium of 3.4 mmol/L. A repeat set is sent 2 hours later and returns at 7.9 mmol/L. In the intervening time the patient has been given 10mg oral morphine and started on a bag of Hartmann’s solution. He is otherwise well and all of bloods are normal. What is the most likely explanation for the second potassium level?
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
blood sample placed on ice and potassium levels:
putting a sample on ice reduces the risk of pseudohyperkalaemia from haemolysis
A 49 year old man is admitted in pulseless ventricular tachycardia. He is resuscitated after a round of CPR and a DC shock. His past medical history includes GORD, diabetes, chronic constipation and chronic kidney disease. His medications include omeprazole, antacids, lactulose, ramipril, sitagliptin and vitamin D. Bloods show magnesium 0.14 mmol/L (0.8-1.2). What is the most likely cause of this presentation?
Omeprazole is a very common cause of hypomagnesaemia. This occurs via inhibition of gut absorption of magnesium
A 78 year old lady is admitted with confusion and hallucinations. Her background includes hypertension, depression, gout, GORD and chronic kidney disease. Her medications include sertraline, ramipril, amlodipine, ranitidine, allopurinol, vitamin D and calcium carbonate. On examination she is euvolaemic and there are no specific findings. A set of tests are performed which return as follows:
Na+ 121 mmol/L(135-145) K+ 4.5 mmol/L(3.5-5) Ur 3.1 mmol/L(2.5-6.7) Cr 83 mmol/L(70-150) TSH 0.93 mU/L (0.5-5.7) Cortisol 940 nmol/L (140-520) Serum osmolality 267 mOsm/kg (275-295) Urine osmolality 503 mOsm/kg Urine sodium 49 mmol/L (<20)
What is the single most likely cause of this presentation?
A. Ramipril
B. Sertraline
C. Amlodipine
D. Ranitidine
E. Allopurinol
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
You are the F1 on call. You have been asked to review the drug chart of a patient with hypertension who has a potassium of 3.0 mmol/l. Which of the following drugs can cause hypokalaemia?
A. Spironolactone
B. Indapamide
C. Ramipril
D. Ibuprofen
E. Amiloride
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.
Hypo vs hyperthyroid causes:
zones of adrenal cortex & what hormones they produce:
(GFR: outside inside glomerulosa, fasciculata & reticularis: salt, sugar, sex: mineralocorticoids, glucocorticoids, androgens vs medulla: catecholamines eg adrenaline/noradrenaline and dopamine)
What condition occurs in both MEN1 and MEN2a?
hyperparathyroidism (parathyroid adenoma/hyperplasia )
What enzyme does allopurinol inhibit?
Xanthine oxidase
What vitamin deficiency causes pellagra?
B3 (niacin)
what does pellagra cause (mnemonic):
3Ds: dementia, dermatitis, diarrhoea
What hormone is produced by fat cells, and has receptors in the hypothalamus?
leptin
mutated gene in Wilson’s disease:
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)
how do ACE inhibitors/ARBs affect potassium levels?
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
ACE inhibitors side effects:
A 28 year old woman has an venous blood gas performed in the emergency department as part of a workup for right loin pain.
She has a negative pregnancy test. Urine dip shows the presence of blood, although she is presently on her period. Her abdomen is soft and non tender.
ED start empirical antibiotics for suspected sepsis given the acidosis.
Inflammatory markers are normal.
pH 7.24
Na 136
K 2.4
Ur 6
Cr 135
Gluc 8.1
HCO3- 16
Cl- 94
Lact 0.7
On review of previous bloods performed at her GP 6 months earlier, she seems to be persistently hypokalaemic.
What is the likely underlying diagnosis?
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
Name a drug used in the treatment of non-acute gout to reduce urate levels by increasing the fractional excretion of uric acid?
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.
In sarcoidosis, production of which enzyme by granulomatous tissue can lead to hypercalcaemia?
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.
You are handed the following VBG while working in the emergency department.
The 24 year old patient has type 1 diabetes and appears very dehydrated.
pH 7.20
BE -12
Na 155mmol/L
K 5mmol/L
Cl 115mmol/L
HCO3 20mmol/L
Glucose 27mmol/L
Lactate 2mmol/L
You are also given the urea (15mmol/L) and serum osmolarity which is 365mmol/L
What is the anion responsible for the patient’s metabolic acidosis?
ketones
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)
ou are handed the following VBG while working in the emergency department.
The patient has coeliac disease and is very unwell, with a blood pressure of 84/36. She describes a 3 day history of productive cough and fevers.
pH 7.21
BE -12
Na 131mmol/L
K 6mmol/L
Cl 109mmol/L
HCO3 12mmol/L
Glucose 3mmol/L
Lactate 2mmol/L
You are also given the urea (6mmol/L) and serum osmolarity which is 290mmol/L. Inflammatory markers are normal.
What condition is responsible for of her metabolic acidosis?
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.
What condition describes inadequate function of the proximal renal tubules of the kidney and is associated with glucosuria, hypophosphatemia and hyperuricosuria?
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
A 54 year old man with type 2 diabetes presents to A&E with low GCS.
He has dry mucous membranes and decreased skin turgor. His wife says he has been going to the toilet more frequently and drinking more for the last few days.
Blood tests show blood glucose 57 mmol/L, serum osmolality high and ketones negative.
What is the diagnosis?
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.
In bile acid synthesis Acyl-CoA cholesterol acyltransferase (ACAT) is the enzyme that converts cholesterol into what?
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.
A patient with chronic kidney disease had a renal transplant and recovered well.
However, on follow-up they are found to have high calcium and a raised PTH.
What is the most likely diagnosis?
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.
What is the most potent pharmacological agent at reducing low density lipoprotein concentration in blood?
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.
A 26 year old man presents to his GP with a yellow nodule on his achilles tendon.
You notice a bluey grey ring around his cornea and yellow irregularly shaped deposits around his eyelids.
Low density lipoprotein (LDL) is raised whereas high density lipoprotein (HDL) and triglycerides are normal.
Genetic studies reveal a LDL receptor mutation.
What is the diagnosis?
Familial Hypercholesterolemia
Arcus senilis (cornea senilis) are lipid deposits that appear as rings on the outer region of the cornea
Lomitapide is a low density lipoprotein lowering drug.
What protein does Lomitapide inhibit?
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.
Which plasma protein is important in the calculation of a corrected calcium level?
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)
The van den Bergh reaction is used to measure serum bilirubin via fractionation. What kind of bilirubin is measured with the direct reaction?
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.
Which drug, used in the treatment of acute gout to reduce inflammation, acts by inhibiting polymerisation of tubulin to reduce motility of neutrophils?
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.
An elderly lady living in a care home has limited mobility and rarely leaves home.
Blood tests find low vitamin D, calcium and phosphate with high PTH and ALP.
What is the most likely diagnosis?
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.
A patient is hypocalcaemic, has an elevated serum phosphate and has an elevated parathyroid hormone (PTH).
Upon examination you notice they have short 4th and 5th metacarpals.
What is the most likely diagnosis?
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.
DiGeorge syndrome mnemonic:
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.)
A 21 year old woman with Borderline Personality Disorder presents to A&E after taking an overdose of medication. Her blood gas shows a metabolic acidosis with respiratory alkalosis. She refuses to tell you what she has taken but does say she has ringing in her ears. What has she most likely overdosed on?
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.
A 29 year old man presents with eruptive xanthomas and a yellow discolouration to the palm.
Blood tests reveal high total cholesterol and triglyceride levels. Genetic studies reveal ApoE2 present.
What is the diagnosis?
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.
In de novo purine synthesis, what kind of feedback do guanylic acid (GMP) and adenylic acid (AMP) have on the enzyme PAT?
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.
What is the name of the cholesterol transport channel targeted by the drug Ezetimibe?
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.
A 24 year old bodybuilder presents to A&E unconscious. He was found at home with low GCS and his flatmate reported he had been shaking and appeared sweaty and confused. He has no past medical history of note. Blood tests show his insulin level is high and C-peptide is low.
What is the most likely cause of his symptoms?
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.
What is the most common joint to be affected in acute gout?
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.
Which protein, found in blood plasma, exchanges triglycerides and cholesterol esters between lipoproteins?
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.
A middle aged man presents to A&E with an exquisitely painful left knee.
He is carrying a half empty bottle and says it contains moonshine.
Blood tests show hyperuricaemia and a low Hb. He is under investigation for a sideroblastic anaemia.
Intoxication of what element is responsible for causing his condition?
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.
In a patient with pseudopseudohypoparathyroidism, what would you expect the serum calcium level to be?
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).
A 43 year old man presents to his GP complaining of very smelly stool that is difficult to flush.
He has been taking a new medication supposed to help him lose weight prior to his bariatric surgery in a few months’ time.
However, he continues to eat takeaways most days of the week.
What medication is this patient most likely taking to explain his symptoms?
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.
A 9 year old boy presents to the GP with enlarged orange coloured tonsils.
Examination elicits a peripheral neuropathy and blood tests show very low plasma HDL levels.
What is the most likely diagnosis?
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.
allopurinol and azathioprine:
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.
GGT and ALP in NAFLD vs AFLD:
a rise in serum ALP and GGT in ALD patients compared to NASH patients.
what ABG result will paracetamol cause? why?
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.
NAFLD vs NASH:
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).
most common cause of liver disease in UK vs worldwide:
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,
Cushing’s disease vs syndrome: how to differentiate?
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.
causes of bitemporal hemianopias:
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.
