Metabolic medicine Flashcards
Where is CRP synthesised? When does this suggest evolving complications?
Levels of CRP are commonly measured in acutely unwell patients. CRP is a protein synthesised in the liver and binds to phosphocholine in bacterial cells and on those cells undergoing apoptosis. In binding to these cells it is then able to activate the complement system. CRP levels are known to rise in patients following surgery. However, levels of greater than 150 at 48 hours post operatively are suggestive of evolving complications.
What are the 6 divisions of BMI and their names?
< 18.5 Underweight Underweight
18.5 - 24.9 Normal Normal
25 - 29.9 Overweight Overweight
30 - 34.9 Obese Obese I
35 - 39.9 Clinically obese Obese II
> 40 Morbidly obese Obese III
What is a glycaemic index?
The glycaemic index (GI) describes the capacity of a food to raise blood glucose compared with glucose in normal glucose-tolerant individuals. Foods with a high GI may be associated with an increased risk of obesity and the post-prandial hyperglycaemia associated with such foods may also increase the risk of type 2 diabetes mellitus.
Give 3 high GI foods?
High GI White rice (87), baked potato (85), white bread (80)
Give 5 medium GI foods?
Couscous (65), boiled new potato (62), digestive biscuit (59), brown rice (58), Porridge (55)
Give 3 low gi foods?
Fruit and vegetables, peanuts
What is hyperkalaemia associated with - alkalosis or acidosis?
Potassium and hydrogen can be thought of as competitors. Hyperkalaemia tends to be associated with acidosis because as potassium levels rise fewer hydrogen ions can enter the cells
Which 4 conditions lead of hypokalaemia with alkalosis?
Hypokalaemia with alkalosis
vomiting thiazide and loop diuretics Cushing's syndrome Conn's syndrome (primary hyperaldosteronism)
Which 4 situations can lead to hypokalaemia with acidosis?
Hypokalaemia with acidosis
diarrhoea renal tubular acidosis acetazolamide partially treated diabetic ketoacidosis
How does magnesium affect potassium?
Magnesium deficiency may also cause hypokalaemia. In such cases, normalizing the potassium level may be difficult until the magnesium deficiency has been corrected
What are 6 causes of hyperkalaemia?
Causes of hyperkalaemia:
acute kidney injury drugs*: potassium sparing diuretics, ACE inhibitors, angiotensin 2 receptor blockers, spironolactone, ciclosporin, heparin** metabolic acidosis Addison's disease rhabdomyolysis massive blood transfusion
What are the ECG changes seen in hyperkalaemia?
ECG changes seen in hyperkalaemia include tall-tented T waves, small P waves, widened QRS leading to a sinusoidal pattern and asystole
What foods are high in potassium?
Foods that are high in potassium:
salt substitutes (i.e. Contain potassium rather than sodium) bananas, oranges, kiwi fruit, avocado, spinach, tomatoes
Give 5 causes of hypokalaemia with hypertension?
Hypokalaemia with hypertension
Cushing's syndrome Conn's syndrome (primary hyperaldosteronism) Liddle's syndrome 11-beta hydroxylase deficiency*
Carbenoxolone, an anti-ulcer drug, and liquorice excess can potentially cause hypokalaemia associated with hypertension
Give 5 causes of hypokalaemia without hypertension?
Hypokalaemia without hypertension
diuretics GI loss (e.g. Diarrhoea, vomiting) renal tubular acidosis (type 1 and 2**) Bartter's syndrome Gitelman syndrome
Which 5 drugs increase potassium?
ACE inhibitors
Angiotensin-2 receptor blockers
Spironolactone
Potassium sparing diuretics (amiloride, triamterene)
Potassium supplements (Sando-K, Slow-K)
Which 3 drugs decrease potassium?
Thiazide diuretics
Loop diuretics
Acetazolamide
What are causes of pseudohyponatraemia?
Hyponatraemia may be caused by water excess or sodium depletion. Causes of pseudohyponatraemia include hyperlipidaemia (increase in serum volume) or a taking blood from a drip arm. Urinary sodium and osmolarity levels aid making a diagnosis
Hyponatraemia with urinary sodium >20mmol
-give 5 causes
Urinary sodium > 20 mmol/l
Sodium depletion, renal loss (patient often hypovolaemic)
diuretics: thiazides, loop diuretics Addison's disease diuretic stage of renal failure
Patient often euvolaemic
SIADH (urine osmolality > 500 mmol/kg) hypothyroidism
Hyponatraemia with urinary sodium <20
-Give 6 causes
Urinary sodium < 20 mmol/l
Sodium depletion, extra-renal loss
diarrhoea, vomiting, sweating burns, adenoma of rectum
Water excess (patient often hypervolaemic and oedematous)
secondary hyperaldosteronism: heart failure, liver cirrhosis nephrotic syndrome IV dextrose psychogenic polydipsia
What is acute hyponatraemia vs chronic? what is mild/mod/severe hyponatraemia?
Management of hyponatremia is complicated and primarily based on the following parameters:
duration of hyponatremia: is it acute or chronic?
acute: develops over a period of < 48 hours
chronic: develops over a period > 48 hours
the severity of hyponatremia: what is the sodium level?
mild: 130-134 mmol/L
moderate: 120-129 mmol/L
severe: < 120 mmol/L
How is chronic hyponatraemia managed if a hypovolaemic cause is suspected?
If a hypovolemic cause is suspected
normal, i.e. isotonic, saline (0.9% NaCl)
this may sometimes be given as a trial
if the serum sodium rises this supports a diagnosis of hypovolemic hyponatraemia
if the serum sodium falls an alternative diagnosis such as SIADH is likely
How is chronic hyponatraemia managed if a euvolaemic cause is suspected?
If a euvolemic cause is suspected
fluid restrict to 500–1000 mL/day
consider medications:
demeclocycline
vaptans (see below)
How is chronic hyponatraemia managed if a hypervolaemic cause is suspected?
If a hypervolemic cause is suspected
fluid restrict to 500–1000 mL/day consider loop diuretics consider vaptans
What are vaptans? who should this be avoided in?
Vasopressin/ADH receptor antagonists (vaptans):
these act primarily on V2 receptors - antagonism of V2 receptors results in selective water diuresis, sparing the electrolytes They should be avoided in patients who have hypovolemic hyponatremia Vasopression/ADH receptor antagonists can stimulate the thirst receptors leading to the desire to drink free water. They can be hepatotoxic in patients with underlying liver disease.
What can happen if hyponatraemia is corrected too quickly? how quickly should Na rise?
Osmotic demyelination syndrome (central pontine myelinolysis)
can occur due to over-correction of severe hyponatremia
pathophysiology:
thought to develop secondary to astrocyte (and possibly oligodendrocyte) apoptosis
astrocytes and oligodendrocytes (cells of the glial syncytium) are crucial for normal myelination
chronic hyponatraemia → loss of osmotically active organic osmolytes (such as myoinositol, glutamate, glutamine) from astrocytes. These provide protection against cerebral oedema
organic osmolytes cannot be replaced quickly enough when the brain volume begins to shrink in response to the correction of hyponatraemia
the dehydrated astrocytes and oligodendrocytes undergo apoptosis or other forms of injury → demyelination
to avoid this, Na+ levels are only raised by 4 to 6 mmol/l in a 24-hour period
symptoms usually occur after 2 days and are usually irreversible: dysarthria, dysphagia, paraparesis or quadriparesis, seizures, confusion, and coma
patients are awake but are unable to move or verbally communicate, also called ‘Locked-in syndrome’
Give 4 causes of hypernatraemia?
-How is this corrected?
Causes of hypernatraemia
dehydration osmotic diuresis e.g. hyperosmolar non-ketotic diabetic coma diabetes insipidus excess IV saline
Hypernatraemia should be corrected with great caution. Although brain tissue can lose sodium and potassium rapidly, lowering of other osmolytes (and importantly water) occurs at a slower rate, predisposing to cerebral oedema, resulting in seizures, coma and death1. Although there are no clinical guidelines by NICE or Royal College of Physicians at present, it is generally accepted that a rate of no greater than 0.5 mmol/hour correction is appropriate1.
Give 3 malignant causes of SIADH?
small cell lung cancer
also: pancreas, prostate
Give 4 neurological causes of SIADH?
stroke
subarachnoid haemorrhage
subdural haemorrhage
meningitis/encephalitis/abscess
Give 2 infective causes of SIADH?
tuberculosis
pneumonia
Give 5 drug causes of SIADH?
sulfonylureas*
SSRIs, tricyclics
carbamazepine
vincristine
cyclophosphamide
What can:
positive end-expiratory pressure (PEEP)
porphyrias
Cause in terms of sodium?
SIADH
What happens to urine osmalality and urinary sodium concentration in SIADH?
Investigations
Urine osmolality: Urine osmolality is inappropriately high (>100 mOsm/kg) in relation to serum osmolality, as the kidneys should normally dilute urine in the setting of low serum osmolality. Urine sodium concentration: Urine sodium concentration is typically high (>40 mmol/L) due to the action of ADH on the renal tubules.
How is SIADH treated?
correction must be done slowly to avoid precipitating central pontine myelinolysis
fluid restriction
demeclocycline: reduces the responsiveness of the collecting tubule cells to ADH
ADH (vasopressin) receptor antagonists have been developed
How is familial hypercholesterolaemia inherited? what does this result in?
Familial hypercholesterolaemia (FH) is an autosomal dominant condition that is thought to affect around 1 in 500 people. It results in high levels of LDL-cholesterol which, if untreated, may cause early cardiovascular disease (CVD). FH is caused by mutations in the gene which encodes the LDL-receptor protein.
When should you suspect familial hypercholesterolaemia? Who should recieve testing for familial hypercholesterolaemia?
Case finding:
NICE suggest that we should suspect FH as a possible diagnosis in adults with:
a total cholesterol level greater than 7.5 mmol/l and/or
a personal or family history of premature coronary heart disease (an event before 60 years in an index individual or first-degree relative)
children of affected parents:
if one parent is affected by familial hypercholesterolaemia, arrange testing in children by age 10
if both parents are affected by familial hypercholesterolaemia, arrange testing in children by age 5
How is clinical diagnosis of familial hypercholesterolaemia made?
Clinical diagnosis is now based on the Simon Broome criteria:
in adults total cholesterol (TC) > 7.5 mmol/l and LDL-C > 4.9 mmol/l or children TC > 6.7 mmol/l and LDL-C > 4.0 mmol/l, plus: for definite FH: tendon xanthoma in patients or 1st or 2nd degree relatives or DNA-based evidence of FH for possible FH: family history of myocardial infarction below age 50 years in 2nd degree relative, below age 60 in 1st degree relative, or a family history of raised cholesterol levels
What is the management of familial hypercholesterolaemia?
Management
the use of CVD risk estimation using standard tables is not appropriate in FH as they do not accurately reflect the risk of CVD referral to a specialist lipid clinic is usually required high-dose statins are usually used first-line first-degree relatives have a 50% chance of having the disorder and should therefore be offered screening. This includes children who should be screened by the age of 10 years if there is one affected parent statins should be discontinued in women 3 months before conception due to the risk of congenital defects
Who should QRISK2 not be used in?
NICE recommend we use the QRISK2 CVD risk assessment tool for patients aged <= 84 years. Patients >= 85 years are at high risk of CVD due to their age. QRISK2 should not be used in the following situations as there are more specific guidelines for these patient groups:
type 1 diabetics patients with an estimated glomerular filtration rate (eGFR) less than 60 ml/min and/or albuminuria patients with a history of familial hyperlipidaemia
Who may QRISK2 underestimate CVD risk for? 4
NICE suggest QRISK2 may underestimate CVD risk in the following population groups:
people treated for HIV people with serious mental health problems people taking medicines that can cause dyslipidaemia such as antipsychotics, corticosteroids or immunosuppressant drugs people with autoimmune disorders/systemic inflammatory disorders such as systemic lupus erythematosus
How should patients with type 1 diabetes be managed for hyperlipidaemia?
Type 1 diabetes mellitus
NICE recommend that we 'consider statin treatment for the primary prevention of CVD in all adults with type 1 diabetes'
atorvastatin 20 mg should be offered if type 1 diabetics who are:
older than 40 years, or
have had diabetes for more than 10 years or
have established nephropathy or
have other CVD risk factors
How should patients with CKD be treated for hyperlipidaemia?
Chronic kidney disease (CKD)
atorvastatin 20mg should be offered to patients with CKD increase the dose if a greater than 40% reduction in non-HDL cholesterol is not achieved and the eGFR > 30 ml/min. If the eGFR is < 30 ml/min a renal specialist should be consulted before increasing the dose
What is the follow up for patients on statins?
NICE recommend we follow-up patients at 3 months
repeat a full lipid profile if the non-HDL cholesterol has not fallen by at least 40% concordance and lifestyle changes should be discussed with the patient NICE recommend we consider increasing the dose of atorvastatin up to 80mg
What is exetimibe? when should this be considered?
Ezetimibe is a lipid-lowering drug which inhibits cholesterol receptors on enterocytes, decreasing cholesterol absorption in the small intestine.
NICE produced guidelines in 2016 on the use of ezetimibe in primary heterozygous-familial and non-familial hypercholesterolaemia
Ezetimibe monotherapy is recommended as an option for treating primary hypercholesterolaemia in adults in whom initial statin therapy is contraindicated or who cannot tolerate statin therapy
Ezetimibe, coadministered with initial statin therapy, is recommended as an option for treating primary hypercholesterolaemia in adults who have started statin therapy when:
serum total or LDL cholesterol concentration is not appropriately controlled either after appropriate dose titration of initial statin therapy or because dose titration is limited by intolerance to the initial statin therapy
a change from initial statin therapy to an alternative statin is being considered.
What is the chemical name for vit a? what can a deficiency cause?
A Retinoids Night-blindness (nyctalopia)
What is the chemical name for vit B1? what can a deficiency cause?
B1 Thiamine
Beriberi polyneuropathy, Wernicke-Korsakoff syndrome, heart failure
What is the chemical name for vit B3? what can a deficiency cause?
B3 Niacin
Pellagra:
dermatitis
diarrhoea
dementia
What is the chemical name for vit B6? what can a deficiency cause?
B6 Pyridoxine Anaemia, irritability, seizures
What is the chemical name for vit B7? what can a deficiency cause?
B7 Biotin Dermatitis, seborrhoea
What is the chemical name for vit B9? what can a deficiency cause?
B9 Folic acid Megaloblastic anaemia, deficiency during pregnancy - neural tube defects
What is the chemical name for vit B12? what can a deficiency cause?
Cyanocobalamin Megaloblastic anaemia, peripheral neuropathy
What is the chemical name for vitC? what can a deficiency cause?
Ascorbic acid Scurvy
gingivitis bleeding
What is the chemical name for vit D? what can a deficiency cause?
Ergocalciferol, cholecalciferol Rickets, osteomalacia
What is the chemical name for vit E? what can a deficiency cause?
Tocopherol, tocotrienol Mild haemolytic anaemia in newborn infants, ataxia, peripheral neuropathy
What is the chemical name for vit K? what can a deficiency cause?
K Naphthoquinone Haemorrhagic disease of the newborn, bleeding diathesis
What is the initial management of hypercalcaemia? what may be used following this?\
Are there any other options?
when are loop diuretics used?
The initial management of hypercalcaemia is rehydration with normal saline, typically 3-4 litres/day. Following rehydration bisphosphonates may be used. They typically take 2-3 days to work with maximal effect being seen at 7 days
Other options include:
calcitonin - quicker effect than bisphosphonates steroids in sarcoidosis
Loop diuretics such as furosemide are sometimes used in hypercalcaemia, particularly in patients who cannot tolerate aggressive fluid rehydration. However, they should be used with caution as they may worsen electrolyte derangement and volume depletion.
Give 7 causes of hypocalcaemia?§
The clinical history combined with parathyroid hormone levels will reveal the cause of hypocalcaemia in the majority of cases
Causes
vitamin D deficiency (osteomalacia) chronic kidney disease hypoparathyroidism (e.g. post thyroid/parathyroid surgery) pseudohypoparathyroidism (target cells insensitive to PTH) rhabdomyolysis (initial stages) magnesium deficiency (due to end organ PTH resistance) massive blood transfusion acute pancreatitis
Contamination of blood samples with EDTA may also give falsely low calcium levels.
Describe acute management of hypocalcaemia?
Management
severe hypocalcaemia (e.g. carpopedal spasm, tetany, seizures or prolonged QT interval) requires IV calcium replacement
the preferred method is with intravenous calcium gluconate, 10ml of 10% solution over 10 minutes
intravenous calcium chloride is more likely to cause local irritation
ECG monitoring is recommended
further management depends on the underlying caus
What is the pathophysiology of hyperuricaemia?
Increased levels of uric acid may be seen secondary to either increased cell turnover or reduced renal excretion of uric acid. Hyperuricaemia may be found in asymptomatic patients who have not experienced attacks of gout
Hyperuricaemia may be associated with hyperlipidaemia and hypertension. It may also be seen in conjunction with the metabolic syndrome
Give 6 causes of increased synthesis of urate?
Increased synthesis
Lesch-Nyhan disease myeloproliferative disorders diet rich in purines exercise psoriasis cytotoxics
Give 5 causes of decreased excretion of urate?
Decreased excretion
drugs: low-dose aspirin, diuretics, pyrazinamide pre-eclampsia alcohol renal failure lead
