Chem path Flashcards
Causes of hypokalaemia
-GI loss: vomiting, diarrhoea
- renal loss: hyperaldosteronism, thiazide and loop diuretics, renal tubular acidosis type 1 and 2
- redistribution into cells: insulin, b-blockers, refeeding syndrome
consequences of hypokalaemia
muscle weakness
nephrogenic DI (polyuria and polydipsia)
ECG changes: T wave flattening, U waves, arrhythmias
normal range of potassium
3.5-5.5mmo/L
investigations and management of hypokalaemia
U&Es
monitor ECG changes
aldosterone:renin ratio (if high suggests conn’s as high aldosterone will negatively feedback on renin)
K replacement:
3-3.5mmol/L –> Oral KCl (2 sandoK tablets, TDS for 48hrs)
<3mmol/L –> IV KCl (10mmol/hr) risk of cardicac arrest
Causes of hyperkalaemia
Artefact- haemolysis when taking blood
intracellular –> extracellular mvmt of K: DKA(insulin shortage), rhabdomyolysis, haemolysis
decreased excretion:
mineralocorticodeficiency (Addisons), K sparing diuretics, ACEi, ARBs, NASAIDs, renal tubular acidosis type 4
Describe the ECG changes in hyperkalaemia
Tall tented T waves
loss of P wave
widened QRS
arrhythmia
management of hyperkalaemia
- repeat bloods incase artefact
- 10mls 10% calcium gluconate (stabilise myocardium)
- 100mls 20% dextrose + 10units short acting insulin eg. actrapid (draws K into cells and dex to prevent hypo)
- nebulised salbutamol
- treat cause
acid- base balance: pCO2 and pH in each met/resp acidosis/ alkalosis
metabolic acidosis- pCO2 low, pH low
metabolic alkalosis - pCO2 high, pH high
respiratory acidosis - pCO2 high, low pH
respiratory alkalosis- pCO2 low, pH high
causes of each met/resp acidosis/ alkalosis
met acidosis:
DKA, renal tubular acidosis, addisons, lactate(shock, sepsis), aspirin, ETOH
met alkalosis
bicarbonate ingesion, Conns, vomiting, burns
resp acidosis
hypoventilation: COPD, opioids, sedatives
resp alkalosis
hyperventilation: panic disorder/ anxiety, asthma,
causes of metabolic acidosis with a high anion gap
KULT
Ketoacidosis
uraemia (renal failure)
lactate
toxins (alcohol, salicylate, mannitol)
equation to calculate the anion gap
normal range
anions- cations
(Na+K)- (Cl+HCO3)
normal range: 14-18mol/L
what is the best marker of liver function?
prothrombin time
causes of isolated raised ALP
physiological: pregnancy (ALPregnancy), growth spurths
pathological: osteoblast activation; Pagets disease, osteromalacia, cholestasis, cirrhosis
why is ALP normal in myeloma?
plasma cells suppress osteoblasts
osteoblast activation secretes ALP
Causes of low albumin
nephrotic syndrome
chronic liver disease
protein losing enteropathy
sepsis
raised GGT and ALP
cholestatic/ obstructive picture
raised GGT in alcoholic liver disease
raised AST:ALT 2:1
supportive alcoholic liver disease
remember ALT- Last in the ratio
raised AST:ALT 1:1
supportive of viral liver disease
ALT>AST
chronic liver disease
what is the INR
it is the prothrombin time (time for the production of thrombin) which has been standardised to age and population and expressed as a ratio of ‘normal’
which clotting factors does the liver synthesise
V, VII, IX, X, XII, XIII
causes of pre, hepatic and post hepatic jaundice
pre hepatic- haemolysis, congestive cardiac failure, thalassaemia
hepatic- viral/ alcoholic hepatitis, cirrhosis, gilberts syndrome, crigler Najjar syndrome
post hepatic- primary biliary cholangitis, sclerosing cholestasis, gall stones, cancer of head of pancreas, cholangio carcinoma
features of acute porphryia
the P’s:
Painful abdomen
peripheral neuropathy
Psychosis
acute abdominal pain and neuropsychiatric Sx (eg. confusion, halluconations)
–> AIP until proven otherwise
HMB (hydroxymethylbilane) synthase deficiency leading to build up of porphobilinogen
what are porphryias
rare metabolic conditions where there is enzyme deficiencies in the haem biosynthesis leading to build up of toxic haem precursors
features of porphyria cutanea tarda
commonest
uroporphyrinogen decarboxylase deficiency
leading to uroporphyrin build up
photosensitivity
facial hyperpigmantation
blistering
milia
scarring
exacerbated by ETOH
describe the combined pituitary function test
administration of GnRH, TRH and insulin then measure levels of pituitary hormones at 0,30,60.90 and 120 mins
thyroxine, glucose, cortisol, LH/FSH, prolactin, TSH, GH
insulin: should raise ACTH and GH
TRH: should raise TSH and prolactin
GnRH: should raise LH/FSH
fasting overnight
pituitary macroadenoma
tumor >1cm
can compress pituitary stalk leading to less dopamine reaching the lactotrophs –> hyperprolactinaemia
can compress optic chiasm - bitemporal hemianopia with superior quadrantinopia
(NB craniopharyngoma causes inferior quadrantinopa)
causes of pseudohyponatraemia
hyperlipidaemia
hyperproteinaemia
Na actually normal but the lipids/proteins take up a large proportion of the serum and dilute the sodium because the conc of Na is calculated by Na/serum vol not Na/H20
how to calculate osmolarity
2(Na+K) + glucose + urea
Enzyme deficiency in acute porphryia
hydroxymethylbilane synthase deficiency
Enzyme deficiency in acute intermittent porphryia
hydroxymethylbilane synthase (same as acute porphryia)
Management of high K on blood test
- repeat blood test as may be artefact
- 10ml 10% calcium gluconate
- 100mls 20% dextrose and 10units short acting insulin
- nebulised salbutamol
Enzyme deficiency in porphyria cutanea tarda and resultant raised intermediate
uroporphyrinogen decarboxylase
raised urinary uroporphyrins and coproporphyrins (pink red flourescence with wood lamp)
Precipitating factors for acute intermittent porphyrias
ALA synthase inducers- steroids, barbituates, ethanol
stress- infection, surgery
reduced caloric intake
features of porphyria cutanea tarda and precipitating factors
photosensitivity
facial hyperpigmentation
blistering
milia
scarring
exacerbated by ETOH
Causes of excess ADH
Lung- SCLC, pneumonia
Brain- traumatic brain ingery, meningitis, tumours
Iatrogenic- SSRIs, amitryptilin, carbamazapine, PPIs
Most common type of thyroid neoplasia
Papillary (75-85%)
Risk for MALT lymphoma
chronic H pylori infection
chronic hashimotos
Histology of medullary cancer of thyroid
sheets of dark cells, amyloid deposition within tumour
Histology of papillary cancer of thyroid
Psammoma bodies (foci of calcification), orphan annie eyes (empty appearing nuclei with central clearing)
Histology of anaplastic thyroid cancer
undifferentiated follicular, large pleomorphic giant cells, spindle cells with sarcomatious appearance
tumour markers for different thyroid cancers
papillary and follicular - thyroglobulin
medullary- CEA and calcitonin
Which neoplasias are involved in MEN1
(3Ps)
Pituitary
Pancreas (insulinoma)
Parathyroid
Which neoplasias are involved in MEN2a
(2P 1M)
Parathyroid
Phaeochromocytoma
Medullary thyroid
Which neoplasias are involved in MEN2b
(1P 2M)
Phaeochromocytoma
Medullary thyroid
Mucocutaneous neuroma
(Marfanoid)
Drug toxicity signs:
Ataxia and nystagmus
Phenytoin
Drug toxicity signs:
Arrhythmias, heart block, confusion, seeing yellow-green
Digoxin
Drug toxicity signs:
tremor, lethargy, fits, arrhythmias, renal failure
Lithium
Drug toxicity signs:
Tinnitus, deafness, nystagmus, renal failure
aminoglycosides
ie. gentamycin, vancomycin
Drug toxicity signs:
Arrhythmias, convulsions, anxiety, tremor
Theophylline
Most common cause of hypercalcaemia
hypercalcaemia of malignancy
X ray appearance of uric acid
radiolucent
X ray appearance of calcium oxalate
radio-opaque
fat soluble vitamins
A, D, E and K
Signs of B3 deficiency
Niacin
Pellagra - B3=3Ds
Dementia
dermatitis
diarrhoea
signs of B6 deficiency
Dermatitis
anameia (sideroblasti)
Signs of B2 deficiency
Riboflavin
Glossitis
features of Bartter syndrome
automomal recessive
defect in thick ascending limb of loop of henle
NKCC2 or ROMK gene mutations
hypokalaemia, alkalosis and hypotension
hypercalcuria
effect of ACE inhibitors on potassium
Causes hyperkalaemia due to reduced potassium excretion
reduced angiotensin II and hence reduced aldosterone therefore reduced excretion
what is an AST and ALT of >2000IU/L indicative of?
paracetamol poisoning
what is Crigler-Najjar syndrome
reduction in UDP glucuronosly transferase needed in the conjugation of bilirubin
more severe version of Gilberts
What is Dublin-Johnson syndrome?
reduced secretion of conjugated bilirubin into bile
raised conjugated bilirubin levels
tumour marker in hepatocellular carcinoma
alpha-fetoprotein
level of plasma cortisol indicative of adrenal insufficiency after short and long synACTHen test
short synACTHen <550nmol/L
long synACTHen <900nmol/L (indicative of primary adrenal insufficiency)
what is Schmidst syndrome
also known as autoimmune polyendocrine syndrome type 2
associated with:
addisons
hypothyroidism and T1DM
vitamin deficiency signs:
ataxia and areflexia
vitamin E deficiency
cause of vitamin B6 deficiency
TB treatment esp isoniazid
features of phenylketonuria
fair haired
developmental delay between 6-12 months
low IQ
features of maple syrup urine disease
impaired metabolism of leucine, isoleucine and valine causing accumulaiton f toxic compounds
encephalopathy- lethargy, poor feeding, hypotonia, seizures
sweet odor and sweaty feet
features of short chain acytl CoA dehydrogenase (SCAD) deficiency
neonatal failure to thrive
hypotonia
metabolic acidosis
hyperglycaemia
functions of the liver
metabolism- glycolysis, glucogen strorage, gluconeogenesis, lipolysis
protein synthesis - plasma proteins, clotting factors
xenobiotic metabolism- P450 rnzyme system, acetylation, coxidation, conjugation
hormone metabolism
Bile synthesis
Reticuloendothelial function- kupffer cells, EPO
contents of bile
bile salts, bilirubin phospholipid, cholesterol, amino acids, steroids, enzymes, porphyrins, vitamins, and heavy metals, as well as exogenous drugs, xenobiotics and environmental toxins
how is bilirubin synthesised?
spleen: RBC –> Heme –> unconjugated bilirubin
blood: unconj-bili albumin complex
liver: unconjugated bili –> conjugated bili
gut: conj bili –> urobilinogen
serum markers of liver cell damage
ALT
AST
ALP
GGT
markers of liver function
albumin
prothrimbin time /coagulation factors
bilirubin
where is ALT present
LIVER
muscle
kidney
brain
pancreas
AST:ALT ratio >2
suggest alcoholic liver disease
isolated raised GGT
alcoholic liver disease
what is raised in biliary system injury
ALP
causes of raised ALP
biliary injury
bone damage
pregnancy
causes of low albumin
chronic liver disease
malnutrition
nephrotic syndrome
protein losing enteropathy
sepsis
what is raised in hepatocellular damage
ALT and AST
how to determine acute from chronnic liver damage
look at albumin- if normal then its acute as albumin as a long half life
Isolated raised ALT <120IU/L
most likely fatty liver so give lifestyle advise
causes of drug induced cholestasis
co-amoxiclav
courvoisier’s sign
painless palpable gall bladder NOT likely to be gallstones (probs pancreatic canceR)
causes of AST >1000IU/L
paracetamol
viruses eg. hepatitis
ischaemia
best marker of acute liver failure
INR
represents synthetic function of liver
?? is this not for chronic?
post op thyrectomy with tingling- what needs to me measured urgently
calcium
- because the surgery may have affected the parathyroids
Pagets disease investigations
ALP raised
plain Xray
technitium bone scan - Tc bisphosphonate scan
Complications of pagets of the skull
conductive deafness- if bone in ears affected
compression of VIII can cause nerve deafness
enzymes increased in acute MI
Troponins
CK
AST
LDH
what happens to potassium after acute MI
it will fall due to an increase in adrenaline
what blood marker is most raised in someone with acute viral hepatitis
Alanine aminotranferase
ALT
what blood marker is most raised in someone with alcoholic hepatitis
aspartate aminotransferase
AST
what is low in primary hyperparathyroidism
vitamin D
blood tests measure 1 alpha hydroxylase levels
in primary hyperPTH this gets converted into activated D3 so it appears that it D is low
what rises in acute dehydration AKI
urea
what rises in chronic renal failure caused by a fall in the GFR
creatinine
good marker of glucose control over the last 3 months
and 3 weeks
3 months HbA1c
3 weeks fructosamine
example of a DDP-4 agonist
-GLIPTINS eg.sitagliptin
Example of an SGLT2 inhibitor
-GLIFOZINS
eg. dapafiglozin
example of GLP1 analogue
exenatide
liraglutide
example of a sulphnyurea
glipizide
glimepiride
MOA of sulphonyureas
increase the secretion of insulin from pancreas
WEIGHT GAIN AND HYPOGLYCAEMIA
MOA of metformin
improves bodies sensitivity to insulin and stops production of glucose in the liver
MOA of SGLT2 inhibitors
act on the sodium glucose transporter in the PCT of the kidney tubules and decreases glucose resorption so causes glucosurea
very effective at lowering glucose PLUS 35% decrease in heart failure and 30% decrease in overall mortality
MOA of glp1 antagonist
Injection
stimulates pancreas to secrete insulin, suppresses glucagon
increase satiety
WEIGHT LOSS
MOA of DPP-4 agonist
metabolite of glp1 and can be taken orally
stimulates pancreas to release insulin, anti glucagon effect
no effect on weight
Example of a thiazolidindiones
pioglitazone
what clotting factors does the liver synthesise
5, 7, 9, 10, 12, 13
orphan annie eyes on histology sign of
papillary thyroid cancer
what are psammoma bodies on histology a sign of?
papillary thyroid cancer
serous cystadenoma (ovarian)
management of phaeochromocytoma
1st: alpha blockade (otherwise b-blockade will lead to unopposed alpha stimulation and hypertensive crisis)
2nd: beta blockade
3rd: surgery when BP well controlled
what conditions are associated with phaechromocytoma
MEN2a
Von hippen lindau syndrome
neurofibromatosis
symptoms and signs of drug toxicity and management:
LITHIUM
metallic taste in mouth
tremor
palpitations
GI upset
polyuria, polydipsia
nausia
blurred vision
hyperPTH and hypercalcaemia
renal stones (high Ca)
reduced GCS and confusion
hyperreflexia
circulatory collapse
convulsions
death
Mx:
STOP lithium
A-E approach
senior review and involve MDT
admit for observation for at least 24hrs
correct any electrolyte abnormalities
haemodialysis in extreme cases
symptoms of drug toxicity and management:\
PHENYTOIN
ataxia
nystagmus
Mx:
supportive treatment
admit for observation
symptoms of drug toxicity and management:
DIGOXIN
arrhythmias
heart block
confusion
seeing yellow-green
Mx:
admit
Digibind
symptoms of drug toxicity and management:
AMINOCLYCOSIDES (vancomycin, gentamycin)
tinnitus
deafness
nystagmus
renal failure
Mx:
stop treatment/ switch to different abx
symptoms of drug toxicity and management:
THEOPHYLLINES
arrhythmia
convulsion
anxiety
tremor
Mx:
stop or reduce dose
symptoms and signs of drug toxicity and management:
LITHIUM
metallic taste in mouth
tremor
palpitations
GI upset
polyuria, polydipsia
nausea
blurred vision
hyperPTH and hypercalcaemia
renal stones (high Ca)
reduced GCS and confusion
hyperreflexia
circulatory collapse
convulsions
death
Mx:
STOP lithium
A-E approach
senior review and involve MDT
admit for observation for at least 24hrs
correct any electrolyte abnormalities
haemodialysis in extreme cases
symptoms of TCA OD
tachycardia
hypotension
reduced GCS
dilated pupils
ataxic gait
flushed hands and feet
thirsty and dry mouth
heart block
enzyme deficient in Gilberts that conjugates bilirubin
uridine diphospho-glucuronosyltransferase
(UDP glucuronyl transferase)
drug used in non-acute gout to reduce urate levels by increasing the fractional excretion of uric acid
probenecid
MOA of allopurinol
xanthine oxidase inhibitor which reduces urate synthesis
what is the mechanism of hypercalcaemia in sarcoidosis
ectopic alpha-1 hydroxylase released by the granulomatous tissue (macrophages)
and release of PTHr peptide
causes of metabolic acidosis with a raised anion gap
GOLDMARK
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]
causes of metabolic acidosis with normal anion gap
ABCD (bicarb lost and replaced with Cl)
Addison’s disease
Bicarbonate loss (diarrhoea, laxative abuse, Renal Tubular Acidosis)
Chloride gain (Sodium Chloride 0.9% infusion)
Drugs (acetazolamide diuretic)
conditions associated with coeliac disease
T1DM
hashimotos
addisons
autoimmune hepatitis
sjogrens
multiple sclerosis
What condition describes inadequate function of the proximal renal tubules of the kidney and is associated with glucosuria, hypophosphatemia and hyperuricosuria?
fanconi syndrome
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 is fanconi syndrome
a disease of the PCT of the tubules resulting in inability to reabsorb substances such as electrolytes and glucose
most potent LDL reducing drug used in familial hypercholesterolemia
evolocumab - a PCKS9 inhibitor
mechanism of lomitapide
inhibits microsomal triglyceride transfer protein (MTP), thereby blocking the release of VLDL from the liver.
what reaction is used to measure conjugated bilirubin
van den bergh
fractionation
MOA of colchicine in gout
reduces inflammation and acts by inhibiting polymerisation of tubulin to reduce migration of neutrophils.
low Ca, high PTH, short 4th and 5th metacarpals diagnosis
pseudohypoparathyroidism
(peripheral resistance to PTH)
features of an aspirin overdose
tinnitus
nausea & vomiting
dizziness
metabolic acidosis with respiratory alkalosis
(This is because salicylates stimulate the respiratory centre causing hyperventilation and inhibit the Krebs cycle resulting in anaerobic metabolism.)
Mutations in familial hypercholesterolaemia
AD- PCSK1, ApoB, LDLR
AR- LDLRAP1
mutations in polygenic hypercholesterolaemia
NPC1L1, HMGCR, CYP7A1
what is familial hyper-a-lipoproteinaemia
deficiency in CETP causing high HDL- relatively benign condition
mutation in phytosterolaemia
ABC G5&G8
where is LDL absorbed
coated pits on the liver have LDLr which then endocytose LDL
causes of secondary hyperlipidaemia
Hormonal- pregnancy, exogenous hormones
metabolic- DM(early onset and MODY), Gout, obesity
renal- nephrotic syndrome, chronic renal failure
alcohol
cause of hypolipidaemia
- Abeta-lipoproteinaemia- autosomal recessive- MTP deficiency affecting long chain fatty acid metabolism
- Tangier disease- HDL def
- hypo-b-lipoprotinaemia- truncted apoB gene
function of PCSK9
binds to LDLR and promotes its degredation
loss of function leads to lower LDL levels
where are bile acids absorbed?
terminal ileum
what transporters are responsible for cholesterol regulation in nd out of the ileum
NPC1L1 cholesterol into circulation
ABC G5&G8 back into gut
what is responsible for HDL uptake into the liver
scavenger receptor B1
SR-B1
role of MTP (and full name)
microsomal triglyceride protease
conjugates cholesterol ester with triglyceride and ApoB to create VLDL
role of ACAT
converts cholesterol into a cholesterol ester in the liver
what mediates the movement of free cholesterol in peripheral cells to HDL?
ABC A1
what ediates the conversion of cholesterol ester in HDL into VLDL and TG into VLDL into HDL
cholesterol ester transfer protein (CETP)
XRay of hand in primary hyperparathyroidism might show
radial aspect cystic changes
when do loosers zones occur
vit D deficiency
what will bone histology show of someone with primary hyperparathyroidism
multinucleate giant cells
-Brown tumours
which enzymes are increased in an acute MI
- Troponins within 2-3hrs
- CK within 6-12 hrs
- aspartate aminotransferase
- LDH
which enzyme is most increased in viral hepatitis
ALT (alanine amino transferase)
viraL
which enzyme is most increased in chronic liver cirrhosis
AST (aspartate aminotransferase)
S-Sirrhosis
which enzyme is most increased in prostate cancer
acid phosphatase aka prostate specific antigen
what is the scan used to diagnose pagets?
Technitium 99 bisphosphonate scan
scan used to look for metastases in oncology
fluorodeoxyglucose (FDG)- positron emission tomogrophy (PET)
label used to scan for primary neuroendocrine tumours
radioactive gallium 68 labelled dotatate (somatostatin)
label used in thyroid scans
Technitium 99 pertechnetate
what scan is used to detect a phaeochromocytoma
Meta-Iodo-Benzyl-Guanidine (MIBG)
what drugs can cause SIADH
sulfonylureas
SSRIs, tricyclics
carbamazepine
vincristine
cyclophosphamide
causes of SIADH
ectopic ADH secretion from SCLC
infections- TB, pneumonia
stroke
SAH/SDH
PEEP
what should the management be for acute, severe, symptomatic hyponatraemia (< 120 mmol/L)
eg presenting with seizures
3% hypertonic sodium chloride
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
Which term is used to describe increased bone density?
osteosclerosis
