Part 1 Viva Flashcards
Causes of respiratory alkalosis
Hypoxia - altitude, anaemia, R-L shunts
Drugs – salicylate, catecholamines etc.
Pulmonary – pneumothorax, haemothorax, pulmonary oedema, pulmonary embolism, aspiration, COPD
Endocrine – pregnancy, hyperthyroidism
CNS – pain, hyperventilation, anxiety, fever, trauma, tumour, meningitis etc.
Causes of a low urea
Hepatobiliary disease due to dec synthesis – acute liver failure, alcohol abuse
Overhydration
Starvation
SIADH
Causes of a high urea
High protein diet
Increased protein catabolism
Dehydration
Renal dysfunction
Shock
Haemorrhage
GI bleed
Causes of hypokalaemia
Inadequate intake - alcoholic, anorexia etc.
Transcellular shift - insulin, ventolin, periodic paralysis etc.
Renal loss - diuretics, vomiting, RTA, Bartter’s syndrome etc.
Extra-renal loss - diarrhoea, laxitives, cancer etc.
Misc – Mg depletion etc.
Further investigation of hypokalaemia
Urine [K], [Cl], plasma [HCO3-], aldo:renin
Bartter syndrome lab findings
Hypokalemic alkalosis
Hypercalciuria/nephrocalcinosis
Increased levels of plasma renin and aldosterone
Biochemical investigation of hyperammonaemia
Mild - exclude artefactual increase and repeat
Exclude heaptic causes (LFTs)
U&E, glucose, Ca, lactate, urine ketones, INR, ABG
Plasma amino acids, urine amino acids, organic acids, orotate, plasma acylcarnitines
Gitelman syndrome lab findings
Hypokalaemic metabolic alkalosis in combination with significant hypomagnesaemia and low urinary calcium excretion
Biochemical investigation of a patient with renal calculi
Single calcium calculus - serum calcium, ionised calcium, and PTH
Recurrent - MC&S, pH, 24 h urinary calcium, phosphate, urate, oxalate, citrate, cystine, creatinine
Stone analysis for components (Fourier Transform InfraRed Spectroscopy)
Causes of low magnesiumm
- Low albumin – biologically active serum Mg is normal
- Electrolyte loss
- GI (malabsorption, diarrhoea, short bowel)
- renal tubular disease, e.g. chronic pyelonephritis, glomerulonephritis, recovery from acute tubular necrosis, post-transplantation - Poor intake - inadequate parenteral nutrition, malabsorption, starvation
- Drugs - thiazides, loop diuretics, aminoglycosides, amphotericin B, cytotoxics, cyclosporine, pentamidine, laxative abuse, proton pump inhibitors, e.g. omeprazole (rare)
- Alcoholism - common (1/3), multiple causes: diet, diarrhoea, renal tubular losses
- Endocrine - hyperthyroidism, hyperparathyroidism, poorly controlled diabetes (osmotic diuresis), hyperaldosteronism, SIADH
- Redistribution - alkalosis, correction of acidosis, severe stress, ‘hungry bone’ syndrome after parathyroid surgery
- Chelation - acute pancreatitis, post-transfusion, foscarnet therapy
- Genetic causes - Bartter, Gitelman syndromes
- Late pregnancy - combination of low albumin and respiratory alkalosis
- High fat diet - up to 10% of patients (mechanism unclear)
Causes of hypoglycaemia in an infant/newborn
- Idiopathic ketotic hypoglycaemia
- Hormonal abnormalities
Insulin excess (non-ketotic)
Counter-regulatory hormone deficiency (ketotic)
eg deficiency of growth hormone or cortisol - Hepatic enzyme deficiencies (ketotic), eg
o Involving glycogen breakdown or synthesis - Glucose-6-phosphatase deficiency, Debrancher deficiency, etc
o Involving gluconeogenesis - Fructose-1,6-diphosphatase deficiency, etc - Other enzyme deficiencies, eg
o Fatty acid oxidation defects (non-ketotic – but not all cases)
o Congenital disorders of glycosylation (phosphomannose isomerase deficiency) - Reaction to drugs or toxins
- Secondary to other systemic disease
Liver failure
Gastroenteritis
CNS disorders
Reye’s syndrome, etc - Iatrogenic – following fundoplication, with gastric tube feeding
Investigation of neonatal hypoglycaemia
o Glucose
o Insulin
o Cortisol
o Growth hormone
o Plasma β-hydroxybutyrate and free fatty acids
o Lactate
o Acylcarnitines (elevated in fatty acid oxidation defects)
o Urine metabolic profile (looking for abnormal patterns of organic acid excretion which may be seen in fatty acid oxidation defects, etc)
o Urine drug screen
o Ammonia (rare possibility of the hyperammonaemia, hypoglycaemia syndrome – activating mutation in glutamate dehydrogenase)
o Other tests – electrolytes and acid-base studies
What substances within the RBC cause interference by haemolysis?
Hb
AST
K
Mg
LDH
Phosphate
Adenylate kinase
Proteases
Rule of thumb: resp compensation for met acidosis?
Winter’s formula: pCO2 = 1.5HCO3 + 8 (+/-2)
Rule of thumb: resp compensation for met alkalosis?
For every 10 mmol/L increase in HCO3, pCO2 should increase by 7 mmHg (by 24 hours)
Expected changes in acute diarrhoea
Expected changes in chronic diarrhoea
Rule of thumb: compensation for acute respiratory acidosis
Every 10mmHg rise in pCO2, 1mmol/L rise in HCO3
Rule of thumb: compensation for chronic resp acidosis
Every 10mmHg rise in pCO2, 3.5 mmol/L rise in HCO3
Rule of thumb: compensation for acute respiratory alkalosis
Every 10mmHg fall in pCO2, 2 mmol/L fall in HCO3
Rule of thumb: compensation for chronic respiratory alkalosis
Every 10mmHg fall in pCO2, 5 mmol/L fall in HCO3
Diagnostic test for protein losing enteropathy
Faecal alpha-1-AT - spot or 24hr clearance
(why - A1AT shows minimal degradation and secretion by GIT, and has similar MW to albumin)
Calculation of 24hr clearance A1AT?
(stool vol x stool [A1AT])/serum [A1AT]
Causes of protein-losing enteropathy
Non GI vs GI
NonGI causes (Lymphatic obstruction vs Cardiac):
Lymphangiectasia
Portal hypertension
Fontan procedure (for univentricular heart)
Congenital heart disease
Congestive heart failure esp RHF
Pericarditis
GI causes (Erosive vs Non-erosive)
Erosive:
IBD primarily Crohn’s
NSAID abuse
Gut malignancy
GVHD
Sarcoidosis
Non-erosive:
Amyloidosis
Collagenous colitis
Sprue
Eosinophilc gastroenteritis
Lupus and ANCA vasculitis, Sjogrens
Causes of increased faecal A1AT
- Protein losing enteropathy
- GI bleeding
- Diarrhoea (obligate loss)
Gold standard test for protein losing enteropathy
Technetium-99m labelled human serum albumin scintigraphy
Causes of low faecal A1AT
Acid degradation (eg Zollinger-Ellison - use PPI)
Causes of distal RTA
Autoimmune diseases are the commonest cause in adults: Systemic lupus erythematosus (SLE), Sjogren syndrome, rheumatoid arthritis, systemic sclerosis, thyroiditis, hepatitis, primary biliary cirrhosis [2].
Drugs: Lithium, amphotericin B, NSAIDs, lead, antivirals, glue sniffing (toluene inhalation in recreational drug abuse)
Inherited, AD or AR: Genetic primary causes of distal RTA include mutations of genes that encode the chloride-bicarbonate exchanger (AE1) or subunits of the H-ATPase pump respectively
Genetic associations: Marfan syndrome, Ehler Danlos syndrome, sickle cell disease, congenital obstruction of the urinary tract
Nephrocalcinosis: Chronic hypercalcemia/familial hypercalciuria, medullary sponge kidney
Tubulointerstitial diseases: chronic pyelonephritis, chronic interstitial nephritis, obstructive uropathy, renal transplant rejection
Hypergammaglobulinemic states: Monoclonal gammopathy, multiple myeloma, amyloidosis, cryoglobulinemia, chronic liver disease
Causes of a proximal RTA
Hypergammaglobulinemic states: Most common cause in adults-monoclonal gammopathy (light chain), multiple myeloma, amyloidosis
Miscellaneous: Interstitial nephritis, Fanconi syndrome, vitamin D deficiency, secondary hyperparathyroidism, chronic hepatitis, idiopathic
Drugs: Lead or other heavy metals, carbonic anhydrase inhibitors (e.g., acetazolamide, topiramate) [4], out of date tetracyclines, aminoglycosides, valproate, mercury, tenofovir, and ifosfamide (nephrotoxic)
Autoimmune: Sjogren syndrome, systemic lupus erythematosus (SLE)
Inherited: AD or AR putative mutations in Na-H antiporter in apical membrane and Na-HCO3 cotransporter in the basolateral membrane of proximal tubular cells respectively
If ferritin is increased due to inflammation, what other test for iron deficiency can be done?
Soluble transferrin receptor 1
What is pyroglutamic acid (5-oxoproline)?
A glutathione precursor. Produced from gamma-glutamyl cysteine by gamma-glutamyl cyclotransferase. Gamma-glutamyl cyclotransferase activity is induced by glutathione depletion - in states of ongoing glutathione depletion, especially if glutathione synthase is inhibited (catalyses gamma-glutamyl cysteine conversion to glutathione), pyroglutamic acid can accumulate.
Risk factors for pyroglutamic acidosis
Elderly
Paracetamol use (glutathione depletion by its metabolite NAPQI)
Sepsis (depletion of glutathione)
Flucloxacillin (inhibits 5-oxoprolinase)
Hepatic and renal impairment
Malnutrition
Pregnancy
Vigabatrin (antiepileptic drug)
Congenital enzyme deficiencies (glutathione synthase deficiency)
Causes of increased homocysteine
Renal impairment
Hypothyroidism
Folate, vitamin B12, and B6 deficiency
Drugs (alcohol)
Expected pattern of B12/folate results in nitrous oxide poisoning?
Normal concentrations total and active B12, increased functional B12 assays (MMA, homocysteine). Functional moieties of B12 - methyl- and adenosylcobalamin replaced by nitrosylcobalamin, impairing it’s ability to convert MMA and homocysteine.
Causes of a discordant low total B12 and normal/increased active B12
Pregnancy (dilutional/reduced haptocorrin)
COCP (same mechanism as pregnancy)
HIV
Myeloma
Severe folate deficiency
What is your lab’s insulin method?
2 site chemiluminescent immunoassay
Interferences with insulin immunoassay?
Insulin autoantibodies
Heterophile antibodies
Interferences with free thyroid hormone assays?
Anti-thyroid hormone antibodies
Heterophile antibodies
Biotin
Definition of neonatal hypoglycaemia
glucose < 2.6mmol/L
Definition of persistent neonatal hypoglycaemia
hypoglycaemia that continues for longer than or starts after 48 hours
Further investigations for neonatal hypoglycaemia
Insulin, GH, cortisol
C-peptide
Ketones, Lactate
Ammonia
Amino acids
Free fatty acids
Urine - ketones, glucose, reducing sugars, urine amino acids, organic acids and acylglycines (urine metabolic screen), drug screen (if suspect exogenous insulin/OHAs)
Causes of neonatal hypoglycaemia
- Hyperinsulinism
- Transient: prem, IUGR, birth asphyxia, maternal PET/DM, intrapartum glucose infusion
- Persistent: Beckwith-Wiedemann syndrome, defects in regulation of insulin secretion - Inadequate glycogenolysis/GNG
- Transient: LBW, SGA, sepsis, hypothermia
- Hormone deficiencies: cortsiol, GH, hypopituitarism
- Severe liver disease
- Inborn errors of metabolism: glycogen storage disease, gluconeogenic defects, fatty oxidation defects, ketogenesis defects, organic acidaemias, galactosaemia, tyrosinaemia type 1
Causes of hypogonadotropic hypogonadism in men
Exogenous androgens
Androgen deprivation therapy
Hypothalamic-pituitary disorders (incl haemochromatosis)
Opioids
Glucocorticoids
Chronic illness
T2DM
Obesity
Sleep apnoea
Causes of increased uric acid
Gout
Preeclampsia
Tumour lysis syndrome
Causes of random error (QC troubleshooting)
Damaged/blocked/poorly aligned sample/reagent pipettor
Aged photometer lamp
Expired reagent
Actions to take if QAP is out
Check units, transcription errors, reconstitution errors (making up QAP sample)
Review internal QC
Check reagent lot changes and calibration results
Check if other labs are having the same problem
Common patterns in QC troubleshooting
Controls in wrong cups (low is high and high is low)
Shift in mean (NLN)
Sawtooth (reagent/QC degradation)
CSF evaluation for meningitis
CSF glucose, lactate, LDH, CRP, adenosine deaminase
CSF evaluation for demyelinating disease
CSF index, oligoclonal banding
What is CSF oligoclonal banding?
Index of intrathecal IgG synthesis
Bands present in CSF but NOT serum
Causes of oligoclonal banding on CSF
Multiple sclerosis
Subacute sclerosing panencephalitis
Neurosyphilis
Neuro-AIDS
Neuro-SLE
Neuro-Behcets
Neurosarcoid
GBS
Cysticercosis
Neuro-Lyme disease
Procalcitonin interpretation
Causes of an increased CK
Analytical - macro CK
Non-exertional (STEEMi)
- Statins and other drugs
- Traumatic/ compressive
- Electrolyte disturbance (hypokalaemia, hypophosphataemia)
- Endocrine (hypothyroidism, acromegaly, thyrotoxic periodic paralysis etc)
- Myopathies (inflammatory- dermatomyositis, polymyositis etc)
Exertional
- Normal muscle: seizures, extreme exercise, environmental heat illness, sickle cell trait, hyperkinetic states
- Abnormal muscle: metabolic and mitochondrial myopathies, malignant hyperthermia/neuroleptic malignant syndrome, dystrophinopathies (muscular dystrophies)
Causes of a hepatitic pattern of abnormal LFTs
Viral (HBV, HCV, EBV, CMV)
Alcohol
NAFLD
Medications (NSAIDs, paracetamol, AEDs)
Haemochromatosis
Alpha-1-antitrypsin deficiency
Autoimmune hepatitis
PBC
PSC
Ischaemic
Causes of a falsely low HbA1c
Pathological:
Increased red cell turnover eg haemolytic anaemia, recent red cell transfusion, recent iron infusion
Chronic liver disease
Pharmacological:
Dapsone
Hydroxyurea
Antivirals (ribavirin, HAART)
Preanalytical/analytical:
Hb variant interference (HPLC/CZE)
Hypertriglyceridaemia (immunoassay)
Short EDTA sample (excessive calcium chelation) (Vitros)
Causes of a falsely increased HbA1c
Pathological:
Iron deficiency with or without anaemia
CKD
B12 deficiency
Alcohol
Pharmacological:
Aspirin
Opiates
Preanalytic/analytical:
Hb variant (HPLC/CZE)
Heterophile antibody
Causes of hypophosphataemia
Intracellular shift: refeeding, IV glucose/insulin, DKA, respiratory alkalosis (complex mech involving glycolysis and increased phosphorylation), burns, hungry bones
Lowered renal phosphate threshold: hyperparathyroidism, iron infusion, renal tubular defects (familial hypophosphataemia, Fanconi syndrome), oncogenic osteomalacia, alcoholism, burns
Decreased intestinal phosphate absorption: vomiting, diarrhoea, phosphate-binding antacids, malabsorption syndrome, vitamin D deficiency, alcoholism
Genetic: X-linked hypophosphataemic rickets, Dent disease
Drugs: Acetazolamide, bisphosphonates, diuretics, oestrogens, HIV therapy, salicylates, TKIs
Causes of cholestatic LFTs
- Intrahepatic - neoplastic (primary or metastatic), infiltrative (amyloidosis, leukaemias, lymphomas), PBC, granulomatous, post-transplant cholangiopathy, AIDS, TPN
- Extrahepatic - gallstones, head of pancreas tumours, cholangiocarcinomas, biliary stricture (congenital biliary atresia), PSC
- Cholestatic hepatitis - drugs eg oestrogens and anabolic steroids, viruses
Metabolic myopathies associated with rhabdomyolysis
Disorders of lipid metabolism and glycogen storage disorders including McArdle’s disease.
DDx methaemoglobinaemia
- Drugs (most common cause) - dapsone, sulfamethoxazole, nitrates
- Hereditary - types I, II, IV, HbM, unstable Hb, G6PD deficiency
Causes of a low anion gap
- High chloride, iodide, bromide
- Decreased albumin
- Increased cations (calcium, magnesium, lithium, proteins)
Causes of increased transferrin
Iron deficiency
Pregnancy
Oestrogen therapy
Hepatitis
Causes of increased serum iron
Recent iron infusion
High biological variability
Iron ingestion/poisoning
Interpretation of serum iron post-poisoning
1-6 hrs post-ingestion
<55: unlikely to lead to clinical toxicity
55-310: mild gut toxicity
>310: liver toxicity
Causes of raised plasma lactate
Preanalytical/analytical: haemolysis, red cell/plt leak, macro-LD
Heart: MI, myocarditis (LD1 and 2)
Liver: hepatocellular damage (LD5)
Skeletal muscle: trauma, muscular dystrophy, dermatomyositis, myoglobinuria (LD 5)
Misc: Infections, CTD, haemolysis, leukemia, pernicious anemia, myeloproliferative disorders, malignancy, renal infarction, pulmonary embolus, hypothyroidism, acute pancreatitis
The only cause of increased plasma albumin
Haemoconcentration
Causes of hypogammaglobulinaemia
Decreased synthesis
Protein loss
Decreased synth: transient (neonates), primary (immunodeficiencies), secondary
Secondary causes of hypogammaglobulinaemia:
Haem- myeloma, CLL, lymphosarcoma
Toxins- uraemia, corticosteroids, cytotoxic, diabetes mellitus, celiac disease
AIDS
Protein loss - skin, gut, kidneys
List the 12 competitive immunoassays we run on Atellica
Anti-TPO
Cortisol
DHEAS
Digoxin
Oestradiol
Folate
FT4
FT3
Homocysteine
Progesterone
Testosterone
Total B12
Causes of false positive GH suppression test
Poorly controlled diabetes mellitus
Malnutrition/malabsorption/anorexia nervosa
Renal disease
Liver disease
Uraemia
Heroin addiction
Causes of low transferrin
Causes of low transferrin
Acute inflammation
Chronic liver disease
Haemochromatosis
Causes of increased angiotensinogen
Hyperthyroidism
Pregnancy/oestrogens
Glucocorticoids
