Chem path Flashcards
What is the most potent LDL lowering drug and what mechanism does it use?
evolocumab - a PCKS9 inhibitor.
features of familial hypercholesterolaemia
blue/grey ring around the cornea (corneal arcus)
yellow nodules (xanthomas) on tendons and around eye lids
high LDH
How are fractions of bilirubin measured?
van der Bergh reaction
the direct reaction of the van der Bergh reaction measures?
conjugated bilirubin
the complete reaction of van der Bergh measures?
total bilirubin
the indirect reaction of can der Bergh measures?
unconjugated bilirubin
what condition is due to the presence of ApoE2
Type 3 hyperlipoproteinemia (Familial dysbetalipoproteinaemia)
increased total cholesterol and triglycerides.
What does a defect in CETP cause?
hyperalphalipoproteinemia 1 (HALP1) where there are raised levels of HDL-cholesterol.
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.
What is the mutation that causes Tangier Disease?
ABCA1 gene.
- inability to release cholesterol from the periphery to be picked up by HDL
- hepatomegaly, splenomegaly, or classically as enlarged orange tonsils in children
- characterised by low HDL levels in the blood conferring an increased risk of cardiovascular disease.
Which term is used to describe increased bone density?
osteosclerosis
e.g. XS vit D; Paget’s, hypoparathyroidism
What is the gold standard investigation for quantification of urinary protein loss, not typically performed in clinical practice?
24 hour urine collection
what feature is characteristic of chronic gout?
tophi
around joints and ear lobes
Most common affected joint in gout?
1st metatarsophalangeal joint
What receptor does ADH affect and where?
V2 receptor in the collecting duct
resulting in water reabsorption
what is the main finding in SIADH
euvolaemia hyponatraemia
low serum osmolality
high urine osmolality
dx of exclusion
what drug can be used in SIADH if it is resisitant to fluid restriction
tolvalptan
V2 antagonist
three causes of euvolaemic hyponatraemia
SIADH
adrenal insufficiency
hypothyroidism
three investigations to rule out euvolaemic hyponatraemia
urine and serum osmolality
short synacthen
TFTs
first line drug for SIADH
demecleocycline
how is Lesch Nyhan syndrome inherited?
x-linked recessive
features of Lesch Nyhan syndrome
developmental delay
self mutilation
young boy
hyperuricaemia
Treatment plan for hyperkalaemia
IV calcium gluconate (cardiac membrane)
IV insulin with dextrose (drive K+ into cells)
Treat underlying cause
What type of DI is lithium therapy associated with
nephrogenic
Features of RTA 1
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+
Metabolic change in RTA 1
metabolic acidosis
Potassium in RTA 1
hypokalaemia
mechanism of RTA 1
Failure of alpha intercalated cells to secrete H+ and resorb K+
Features of RTA 2
Type 2 (Proximal Renal Tubular Acidosis)
Moderate metabolic acidosis
Hypokalaemia
Failure of proximal tubular cells to reabsorb HCO3-
Metabolic change in RTA 2
moderate metabolic acidosis
potassium in RTA 2
hypokalaemia
mechanism of RTA 2
Failure of proximal tubular cells to reabsorb HCO3-
features of RTA 4
Type 4 (Hyperkalaemic RTA)
Adrenal failure
Mild reduction in serum pH
Hyperkalaemic
Caused by a deficiency of aldosterone
potassium in RTA 4
hyperkalaemia
mechanism of RTA 4
aldosterone deficiency/ Addisons/ Adrenal failure
What is RTA
series of heterogenous conditions which describe the failure of the body to acidify the urine
What is Paget’s disease of the bone?
focal disorder of bone remodelling with increased bone turnover
leads to localised areas of poorly organised bone overgrowth causing fractures and deformities
Patients may present with localised pain and warmth, loss of hearing and bowing of the legs.
What is the only biochemical abnormality detected in Pagets
Alkaline Phosphatase (ALP)
due to the increased action of osteoblasts.
ECG changes in hyperkalaemia
- tall peaked (tented) T waves
- a shortened QT interval
- loss of P waves.
can progress to sinusoidal wave
how do you assess for a true hyponatraemia?
serum sodium and serum osmolality
A low serum osmolality tells you this is a true hyponatraemia.
A normal or high serum osmolality tells you this is a pseudohyponatraemia.
What is Chvostek’s sign?
Hypocalcaemia: involves tapping the facial nerve just anterior to the external auditory meatus and will cause ipsilateral contraction of the facial muscles
what is trousseau sign?
Hypocalcaemia: blood pressure cuff is used to occlude the brachial artery for a few minutes, may demonstrate spasms of the muscles of the hand and forearm.
How can rhabdomyolysis be diagnosed?
A serum creatine kinase measurement greater than 5 times the upper limit of normal
Raised serum myoglobin which leads to myoglobinuria (Dark brown urine)
what is a normal anion gap range
14-18
how do you calculate anion gap
(Na + K) - (Cl + HCO3)
Causes of raised anion gap
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]
KULT
K- Ketoacidosis
U- Uraemia
L- Lactate
T- Toxins: glycols, salicylates, oxoproline
Causes of normal anion gap
Hyperalimentation
Addison
RTA (bicarb loss)
Diarrhoea (bicarb loss)
Acetozolamide
Spironolactone
Saline (chloride gain)
how do you calculate osmolality
2Na + urea + glucose
osmolality is measured where
lab
osmolarity is measured where
by you
where is cholecalciferol converted to 25-hydroxycholecalciferol?
by what enzyme?
liver
by 25 hydroxylase
What HbA1c is normal?
< 42 mmol/mol
what is the difference in action between alendronic acid and denosumab
Bisphosphonates reduce bone turnover and hence can prevent progression of osteoporosisBisphosphonates do not directly increase bone density. The only treatment that directly increases bone density in osteoporosis is denosumab.
what is the MoA of orlistat
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.
what does a Hypoglycaemia with high insulin and low C-peptide suggest
exogenous source of insulin
what does a Hypoglycaemia with high insulin and high C-peptide suggest
endogenous source of insulin
- insulinoma
- inborn errors of metabolism
- sulfonylureas due to increased release of endogenously produced insulin
How can you exclude factitious hypoglycaemia?
A Sulfonylurea screen is useful in distinguishing an insulin-secreting tumour from surreptitious sulfonylurea ingestion.
Factitious hypoglycaemia may be caused by surreptitious use of insulin or sulfonylureas
ApoE4 classically gives an increased risk of developing which neurodegenerative condition?
Alzheimer’s disease
The T score in DEXA scans describes?
how bone density varies compared to that of a young healthy population
T for Teenagers
The Z score in DEXA scans describes?
describes how the patient’s bone mass varies compared to an age matched control and is useful in identifying accelerated bone loss relative to age
Where in the gut are bile acids reabsorbed?
terminal ileum
This enterohepatic circulation of bile acids minimises the conversion of cholesterol into new bile acids.
how does cholestyramine work to reduce cholesterol?
binds to bile acids in the gut stopping them from being reabsorbed
liver then has to convert greater amounts of cholesterol into bile acids in order to maintain adequate secretion of bile acids into the biliary system, lowering cholesterol levels
Vitamin D def effect on calcium
low
Vitamin D def effect on phosphate
low
Vitamin D def effect on ALP
raised
What class of drug must not be co-administered with azathioprine in individuals with TPMT deficiency, else a potentially fatal buildup of toxic metabolites may occur?
Xanthine Oxidase inhibitors e.g. allopurinol
results in profound leukopenia and death
Levels of what enzyme must be checked before starting azathioprine?
Thiopurine methyltransferase
TPMT deficiency is a congenital deficiency in an enzyme used to convert 6-mercaptopurine, a breakdown product of azathioprine, into less toxic, excretable metabolites.
Leads to a buildup of toxic metabolites that may lead to profound leukopenia and death.
Which enzyme forms the rate limiting step in de novo purine synthesis?
Phosphoribosyl pyrophosphate amidotransferase (PAT)
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.
Blood tests show grossly raised levels of plant sterol in blood. Which autosomal recessive disorder do they have?
Phytosterolemia
The raised levels of non-cholesterol sterols presents with premature atherosclerosis and tendon xanthomas.
Which proteins are involved in regulating the absorption and excretion of cholesterol and non-cholesterol sterols.
ABCG5 and ABCG8
genes encoding transporter proteins sterolin-1 and -2 respectively
Causes of Fanconi syndrome
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
Signs and symptoms of fanconi syndrome
Polyuria, polydipsia and dehydration (due to glucosuria)
Growth failure (in children)
Metabolic acidosis (Type 2 Renal Tubular Acidosis)
Hypokalaemia
Proteinuria
Hyperuricosuria
what are the two ways 6-mercaptopurine are cleared from the body
TPMT and xanthine oxidase
Under polarised light, what colour would you expect needle shaped crystals to appear when parallel to a red filter?
orange
Under polarised light, what colour would you expect needle shaped crystals to appear when perpendicular to a red filter?
blue
in rickets, what are the bony abnormalities
Widening of the bones at the wrist and knees (sites of rapid bone growth)
bowing of the legs
impaired fasting glucose
fasting plasma glucose between 6.1 - 6.9 mmol/L
impaired glucose tolerance
2 hour oral glucose tolerance test plasma glucose 7.8 - 11.0 mmol/L.
why is there raised phosphate in CKD
inability to excrete phosphate
features of salicylate overdose
N&V
room spinning
high pitched tinnitus
tachypnoea, resp distress
fever
features of paracetamol overdose
abdo pain
N&V
liver damage/failure
ABCD of normal anion gap
Addisons
Bicarbonate loss
Chloride again
Drugs e.g. acetozolamide
In familial hypocalciuric hypercalcaemia (FHH), which receptor has suffered a mutation?
Calcium Sensing Receptor
In FHH a mutation of this receptor causes it to be relatively insensitive to calcium
This results in a greater release of PTH in response to a normal calcium level (overall greater calcium retention)
what does the Calcium Sensing Receptor regulate?
PTH release
where is the Calcium Sensing Receptor found
parathyroid gland
how can familial hypocalciuric hypercalcaemia be differentiated from primary hyperparathyroidism
calcium/creatinine clearance ratio measured from a 24 hour urine collection tends to be lower in FHH than in primary hyperparathyroidism.
what gene is tested for to diagnose FHH
CASR
What vitamin converts cyanide to a renally cleared, less toxic, metabolite and is the first line medication for cyanide poisoning?
hydroxocobalamin
Vitamin A
retinol
Vitamin B1
thiamine
Vitamin B2
riboflavin
Vitamin B3
niacin
vitamin B6
pyridoxine
vitamin B12
cobalamin
vitamin C
ascorbate
vitamin D
cholecalciferol
vitamin E
tocopherol
vitamin K
phytomenadione
Excess Vitamin A
Exfoliation hepatitis
Deficiency in Vitamin A
colour blindness
test for vitamin A
serum
deficiency in vitamin B1
Beri-Beri
Neuropathy
Wernicke Syndrome
test for vitamin B1
RBC transketolase
deficiency in vitamin B2
Glossitis
test for vitamin B2
RBC glutathione reductase
deficiency in vitamin B3
Pellagra
– 3Ds Dementia, dermatitis, diarrhoea
deficiency in vitamin B6
Dermatitis/ anaemia
excess vitamin B6
Neuropathy
test for vitamin B6
RBC AST activation
deficiency in vitamin B12
Neuropathy
sub-acute combined degeneration of the cord
test for vitamin b12
serum b12
deficiency in vitamin C
scurvy
excess in vitamin C
renal stones
test for vitamin C
plasma
deficiency in folate results in
neural tube defects
megaloblastic anaemia
test for folate
RBC folate
deficiency in vitamin D
rickets
osteomalacia
excess vitamin D
hypercalcaemia
test for vitamin D
serum
deficiency in vitamin E
Anaemia /neuropathy/IHD
test for vitamin E
serum
deficiency in vitamin K
clotting problems
test for vitamin K
PT
excess iron
haemochromatosis
deficiency in iron
hypochromoc anaemia
test for iron
FBC
Fe and binding studies
Ferritin
deficiency in iodine
hypothyroidism
goitre
excess iodine
Hypo/Hyperthyroid (Jod-Basedow/Wolf- Chaicoff effects)
tests for iodine
TFTs
deficiency in zinc
dermatitis
deficiency in copper
anaemia
test for copper
Cu
caeruloplasmin
excess in copper
Wilson’s disease
deficiency in fluoride
dental caries
excess in fluoride
fluorosis
vitamin deficiency in Crohns
B12 deficiency
fat-soluble vitamins (ADEK)
vitamin deficiency in coeliac
Iron deficiency
Vitamins ADEK
thiamine
Vitamin B6
folate
vitamin deficiency in CLD
Vitamins ADEK
B12
Selenium
Magnesium
Zinc
folate
vitamin deficiency in CKD
Protein energy wasting syndrome
vitamin deficiency in pancreatic insufficiency
Vit ADEK
what is refeeding syndrome
Refeeding syndrome describes the physiological consequences of rapid reintroduction of nutrition to a chronically malnourished person. This causes fluid shifts which result in electrolyte abnormalities. Refeeding syndrome can lead to cardiac failure and is potentially fatal.
features of cyanide poisoning
inhalation of smoke in house fire
confusion
coughing up black sputum
bitter almond taste
tachycardia
hypertensio
first degree AV block
What is the most important blood test in the assessment of an unconscious patient?
blood glucose
what complication is most commonly associated with rapid corrections of hyponatraemia
central pontine myelinolysis
what are the two pathways that purine can be synthesised
de novo
salvage pathway
which purine synthesis pathway predominates in most tissues and is more efficient
salvage
What is the inheritance pattern of Gilbert’s syndrome?
autosomal recessive
what sort of bilirubinaemia does Gilberts cause
isolated unconjugated hyperbilirubinaemia
what dermatological finding is associated with insulin resistance
acanthosis nigricans
what can be the cause of a low anion gap
hypoalbuminaemia
how can you distinguish chronic and acute respiratory acidosis/alkalosis?
the degree of metabolic compensation
What does Cholestyramine bind to in the gut in order to cause the liver to break down more cholesterol?
bile acids
What do bacteria in the gut convert bilirubin into which gives stool its characteristic brown colour?
stercobilin
is unconjugated bilirubin water soluble
no
is unconjugated bilirubin lipid soluble
YES
is conjugated bilirubin water soluble
yes
how is conjugated bilirubin removed in the faeces
bacteria in the gut convert it into stercobilin via stercobilinogen
stercobilin gives stool its brown colour
Looser’s zones are a pathognomonic X-ray finding of which condition?
osteomalacia
pseudofractures lying perpendicular to the surface of the bone. They are seen in osteomalacia as a result of defective bone mineralisation and are often bilateral and symmetrical.
What kind of inheritance is shown by the Multiple Endocrine Neoplasia syndromes?
autosomal dominant
men dominant
how is osmolar gap calculated
osmolality (lab) - osmolarity (your calc)
what is normal osmolar gap
<10
how is osmolality calculated
2(na+k) + glucose + urea
what can a raised OSMOLAR gap be due to
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
- methanol
when is the Guthrie test done
6 days
what condition are checked for in Guthrie test
Phenylketonuria
congenital hypothyroidism
cystic fibrosis
sickle cell disease
MCAD (medium chain acylCoA dehydrogenase) deficiency
what causes phenylketonuria
phenylalanine hydroxylase deficiency
how do you screen for PKu
phenylalanine levels
what causes congenital hypothyroidism
dysgenesis/agenesis of the thyroid gland
screen with TSH
what causes cystic fibrosis
Mutation in CFTR - viscous secretions → ductal blockages
how do you assess for cystic fibrosis
immune reactive trypsin
if positive do a DNA mutation detection test
what is Medium Chain AcylCoA dehydrogenase Deficiency
Fatty acid oxidation disorder
how is Medium Chain AcylCoA dehydrogenase Deficiency detected
Acylcarnitine levels by tandem Mass Spectrometry
what does Specificity mean?
probability (in %) that someone without the disease will correctly test negative
85 people without CF in total, and 80 actually test negative. Specificity is 80/85=94% (much easier to think like this than memorise formulae!)
what does Sensitivity mean
the probability that someone with the disease will correctly test positive
100 people with CF in total, and 90 actually test positive. Sensitivity is 90/100=90%
what does positive predictive value mean?
probability that someone who tests positive actually has the disease
95 people tested positive of which 90 had the disease. PPV= 90/95 = 95%
what does negative predictive value mean?
probability that someone who tests negative actually doesn’t have the disease
90 people test negative, 80 didnt have the disease. NPV= 80/90= 89%
what is ornithine transcarbamylase deficiency
key features
urea cycle disorder
- High ammonia (>200uM) leading to encephalopathy and developmental delay
- Respiratory alkalosis
- Vomiting?diarrhoea
- Treat with low protein diet (stops urea formation)
what do urea cycle disorders result in
high ammonia
how are urea cycle disorders inherited
autosomal recessive
which urea cycle disorder is not autosomal recessive
ornithine decarboxylase deficiency
why are glutamine levels high in urea cycle disorders
The body is incapable of excreting a very high level of ammonia, so, instead, the body will attach an ammonium group to glutamate to make glutamine
This means that plasma glutamine in hyperammoniaemic conditions will be high
treatment of urea cycle disorders
Remove ammonia (using sodium benzoate or sodium phenylacetate or dialysis)
Reduce ammonia production (low protein diet)
what is the metabolic state in organic acidurias
Hyperammonaemia with Metabolic ACIDOSIS and High Anion Gap
what causes organic acidurias
These are caused by defects within the complex metabolism of the branched chain amino acids (leucine, isoleucine and valine)
key features of organic acidurias
funny smelling urine
High urea, ketones
Metabolic acidosis
features of a child with PKU
blue eyes and fair hair/skin Retardation
two examples of aminoacidopathies
PKU
Maple Syrup Urine Disease
characteristic feature in maple syrup urine disease
sweaty feet
what do Mitochondrial Fatty Acid Beta-Oxidation disorders cause
hypoketotic hypoglycaemia
If you are unable to make ketones, it suggests that you are unable to break down fatty acids
Mitochondrial Fatty Acid Beta-Oxidation disorde example
MCADD
features of MCADD
hepatomegaly
cardiomyopathy
rhabdomyolysis
how do you screen for MCADD
Screened with blood acylcarnitine
Test urine organic acids
Treat with regular carbohydrate
what is galactosaemia
disorder of breaking down carbohydrates
avoid milk
what is the most severe form of galactosaemia
Galactose-1-phosphate uridyl transferase (Gal-1-PUT) deficiency
also the most common
key presenting feature of galactosaemia
conjugated hyperbilirubinaemia
poor feeds
retinopathy
what is Von Gierke disease
a glycogen storage disorder
what happens in a glycogen storage disorder
Whenever you break down glucose, you make glucose-1-phosphate or glucose-6-phosphate and then the phosphate groups have to be removed (because they are high energy groups meaning that the molecule CANNOT get across the membrane with the phosphate attached)
Without a phosphatase, the G6P and G1P cannot be exported
This results in your muscles and your liver building up loads of glycogen which cannot be liberated and so you become hypoglycaemic
key finding in glycogen storage disorder like Von Gierke
hypoglycaemia
MELAS, Kearn’s, Sayre, POEMS are all examples of
mitochondrial disorders
CDG type 1a is a type of
glycosylation disorder due defect of post-translational protein glycosylation
how do you investigate glycosylation disorder
Measure serum transferrins
what is diagnostic of mitochondrial disorders
high lactate and CK
Muscle biopsy diagnostic
what type of disorder is Tay Sachs
Lysosomal disorders
Very slow progressing
Neuroregression, hepatosplenomegaly Cardiomyopathy
Test urine mucooligopolysaccharides and WBC enzyme levels
difference in pH in HHS and DKA
DKA < 7.3
HHS > 7.3
osmolality in HHS
> 320
blood glucose in HHS
> 30
In general, what pH imbalance is associated with hypokalaemia?
alkalosis
low potassium means, potassium leaves cells into blood in exchange for protons causing an alkalosis
Hyperinsulinaemic hypoglycaemia causes [3]
- Insulin overdose
- Sulfonylurea excess
- Insulinoma
hypoinsulinaemic hypoglycaemia causes
+ve ketones
o Alcohol binge with no food
o Pituitaryinsufficiency
o Addison’s
o Liverfailure
-ve ketones
o Non pancreatic neoplasms
o Fibrosarcomata
o Fibromata
main investigation finding in Conn’s syndrome
raised aldosterone:renin levels
main investigations in phaeochromocytoma
Plasma and 24h urinary metadrenaline measurement/ catecholamines & VMA
main investigation for Cushings
1st line: Overnight dexamethasone suppression test or 24h urinary free cortisol. +ve suggests true Cushing’s syndrome
inferior pituitary petrosal sinus sampling
main investigation for Addison’s
SynACTHen test
glucose levels in Addisons
low
how do you differentiate ectopic ACTH and pituitary ACTH secretion
using high dose dexamethasone
low dose dexamethasone does not suppress ectopic ACTH
reasons for hypernatraemia in a neonate
dehydration
overly concentrated milk formula
reasons for hypernatraemia in a neonate
dehydration
overly concentrated milk formula
reasons for hyponatraemia in a neonates
excess water intake
immature tubular function
factitious
CAH
normal GFR
120 ml/hr
age related decline in GFR rate
1ml/hr/yr
definition of clearance
the volume of plasma that can be completed cleared of a marker substance in a unit of time.
when can clearance = GFR
If marker is not bound to serum proteins, freely filtered by the glomerulus, and not secreted/reabsorbed by tubular cells
gold standard measure of GFR
inulin
which endogenous marker is used for assess renal function
creatinine
gold standard for assessing proteinuria
protein:creatinine ratio (PCR)
3 definitions of AKI
1- Rise in serum creatinine over 26 within 48h
2- A 50% or greater rise in serum creatinine known or presumed to have occurred within the past 7 days
3- A fall in urine output to less than 0.5mL/kg/hour for more than 6 hours.
what are the 5 indiciations for dialysis
AEIOU
a- acidosis
e- electrolyte disturbance e.g. refractory hyperkalaemia
I- intoxication e.g. lithium ,aspirin
o- overload (fluid) e.g. pulmonary
u- uraemic encephalopathy
how is haemodialysis delievered
tessio line or AV fistula
how is peritoneal dialysis delivered
via a Tenckoff catheter using the peritoneum as a dialysis membrane
done at home
which life long immunosuppression is used post kidney transplant
tacrolimus or ciclosporin
which scar shows a kidney transplant may have been done for the patient
Rutherford Morrison (hockey stick)
4 consequences of CKD
- homeostasis failure
- hormonal function failure
- cardiovascular disease
- uraemia and death
what is the defect in maple syrup urine disease
alpha ketoacid dehydrogenase
low sodium but high serum osmolality
glucose/mannitol infusion
low sodium but normal serum osmolality
pseudohyponatraemia
drip arm sample
what is TURP syndrome
hyponatraemia from irrigation absorbed through damaged prostate
Hyperaldosterone picture with raised Na, low K, HTN but raised renin
renal artery stenosis
Man who has been in a car accident, raised sodium and plasma osmolality, low urine osmolality
Cranial diabetes inspidus
what would the urinary sodium be in a hypovolaemic patient
low
attempt to retain water
exception is diuretics where sodium will be high in the urine regardless
diagnostic criteria for SIADH
True hyponatraemia (<135)
low plasma/serum osmolality (<270)
high urine sodium (>20)
high urine osmolality (>100)
no adrenal/thyroid/renal dysfunction
low serum high urine
most common cause of SIADH
small cell lung cancer
what does aldosterone stimulate the transcription of
ENaC channels
causes of hyperkalaemia
- Reduced GFR
- Reduced renin activity
o Type 4 renal tubular acidosis (diabetic nephropathy)
o NSAIDs - ACE inhibitors
- Angiotensin receptor blockers
- Addison’s disease
- Aldosterone antagonists
- Potassium release from cells
causes of hypokalaemia
- GI loss
- Renal loss
o Hyperaldosteronism, Cushing’s syndrome
o Increased sodium delivery to the distal nephron
o Osmotic diuresis - Redistribution into cells
o Insulin
o Beta agonists
o Alkalosis - RARE causes:
o Renal tubular acidosis type 1 and 2
o Hypomagnesaemia
how you distinguish between a prolactinoma and a non-functional adenoma?
prolactin levels in prolactinoma >6000
prolactin levels in non-functional adenoma 1000-5000
Raised prolactin, raised TSH, raised T4
TSHoma
what is the preferred investigation for cushings
inferior petrosal sinus sampling
test for Addisons
short synacthen
low plasma sodium, low urine sodium
primary polydipsia
what is the water deprivation test finding for primary polydipsia
urine does concentrate but not to normal levels (400-600)
what enzyme is raised in mumps
amylase-S
phosphate levels in secondary hyperparathyroidism vs osteomalacia/rickets
high in secondary due to CKD making it difficult to excrete phosphate leading to this retention
low in osteomalacia due to vitamin D deficiency as low vitamin D means no phosphate absorption from the gut
how can glucose be given to a hypoglycaemic patient with no IV access
IM glucose
acute treatment options for gout
NSAIDs
colchicine
corticosteroids
chronic treatment options for gout
allopurinol
probenecid
which enzyme is elevated in cardiac failure
brain natriuretic peptide
A man develops signs of hyperthyroidism. Bloods show low TSH and high thyroxine. A technetium scan shows no uptake. What is the likely diagnosis?
de quervains
normal range for urine specific gravity
1.005 and 1.030
21 hydroxylase deficiency
most common
low aldosterone
high sex hormones
second most common cause of CAH
11 beta hydroxylase def
which cause of CAH leads to a salt losing crisis
21 hydroxylase
which enzyme deficiency allows for mineralocorticoid activity
11 beta hydroxylase activity
why does an insulinoma reduced FFA levels
insulin suppresses lipolysis
