Clinical Biochemistry Flashcards
define accuracy
closeness to the true value
define precision
reproducibility of agreement with each other for multiple trials
define true value
standard or reference of a known or theoretical value
what results show in a blood sample that has been haemolysed?
collected too vigorously
red cells have been broken down
artificially high level of potassium
describe how a false negative occurs
there is a proportion of the diseased population, where for the result of the test, fall into the reference range
define sensitivity
true positive / true positive + false negative
define specificity
true negative / true negative + false positive
what factors affect reference ranges and results?
age gender diet pregnancy sample handling sample type time of day/month/year weight fasting posture sample collection procedure
where is calcium distributed in the body?
99% in bone
1% in plasma
of that, 50-60% is bound to plasma proteins
remainder is ionised (active, required for nerve conduction and muscle contraction)
what affects plasma calcium concentration?
alteration in protein levels
vitamin D
parathyroid hormone
renal function
prolonged tourniquet application (increases protein levels)
reduced/increased by 0.02mmol for each g albumin falls below/above 40
what is the role of parathyroid hormone?
released when Ca levels fall
increases renal reabsorption of Ca and excretion of PO4
stimulates osteoclasts, increases bone reabsorption and increases Ca released from bone
increases vitamin D synthesis
describe vitamin D metabolism
UV light converts cholesterol to vitamin D3
hydroxylated at 25 site in the liver
converted from vitamin D to 1,25 vitamin D (active form) in the kidneys
what are the causes of hypercalcaemia?
PTH excess vitamin D excess (ingestion, sarcoid) increased Ca intake (milk-alkali syndrome in PUD) thiazide diuretics bony metastases in malignancy PTH-secreting tumours haematological malignancy thyrotoxicosis addison's disease familial hypocalcuric hypercalcaemia
what are the signs and symptoms of hypercalcaemia?
malaise depression polydipsia polyuria abdominal pain (renal stones) features of underlying disease (malignancy, sarcoid) low PO4 and high Ca (excess PTH) high PO4 and Ca (excess vitamin D) high ALP (bone disease, haematological malignancy) renal function CXR (sarcoid) plasma protein electrophoresis (myeloma) urinary calcium
what is the management of hypercalcaemia?
rehydration (orally, normal saline 4-6L over 24hrs)
monitor urine output
loop diuretic (furosemide)
monitor K levels if lots of excretion
bisphosphonates (bind Ca to prevent if being released from bone)
hydrocortisone (in myeloma or sarcoid)
what are the causes of hypocalcaemia?
not corrected for albumin renal failure (increased PO4 and vitamin D may not be converted to the active form) hypoparathyroidism vitamin D deficiency hypomagnesaemia bisphosphonates
what are the symptoms and signs of hypocalcaemia?
neuromuscular irritability
tetany
positive Chvostek’s sign (tap on facial nerve and spasm of facial muscle)
positive Trousseau’s sign (inflation of BP cuff causes wrist flexion and finger extension)
QT prolongation
what is the management of hypocalcaemia?
oral calcium
milk
vitamin D
IV calcium gluconate (severe cases)
describe the storage and uses of PO4
85% stored in bone within cells
required for ATP
important constituent of cell membranes and nucleic acid
what are the causes of hypophosphataemia?
poor diet, reduced intake reduced absorption (malnutrition, vitamin D deficiency) increased shift into cells (respiratory alkalosis, insulin, glucose, amino acids) increased urinary excretion (excessive PTH, renal tubular defects)
what are the clinical features of hypophosphataemia?
refeeding syndrome, post IV, enteral or normal feeding alcohol abuse asymptomatic rhabdomyolysis cardiomyopathy renal failure impaired RBC function impaired white cell function (susceptible to infection) reduced phagocytosis
what is the treatment of hypophosphataemia?
milk
oral supplements
IV dipotassium hydrogen phosphate over 12hr and once in 24hr (too much causes calcium deposits in tissues)
what are the causes of hyperphosphataemia?
renal failure
cellular phosphate leak
cell breakdown (rhabdomyolysis or tumour lysis)
describe the storage of magnesium
67% in bone
31% intracellular
what are the causes of hypomagnesaemia?
poor intake
malabsorption
increased losses (renal or GI)
diarrhoea or fistula (losses of gut fluid)
refeeding syndrome
alcohol abuse/withdrawal
increase in amount of fluid lost in the loop of henle
what are the symptoms and signs of hypomagnesaemia?
similar to hypocalcaemia
tetany
Chovstek’s sign
neuromuscular problems
what is the treatment of hypomagnesaemia?
oral or IV magnesium
30mmol in first 24hrs then 20mmol in each 24hr period after that (IV)
where is ALP found?
liver
bone
intestines
placenta
what are the causes of high ALP?
bone growth
pregnancy (placenta)
bone fracture healing
bony metastases
Paget’s disease (excessive bone growth and abnormal bone remodelling)
hyperparathyroidism (osteoclasts stimulated to release Ca)
obstructive jaundice
describe osteoporosis
Ca, PO4 and ALP normal
asymptomatic
usually found in a DEXA scan if there are no fractures
describe osteomalacia
defective bone mineralisation (similar to rickets)
low Ca and PO4 and high ALP
usually due to low vitamin D
describe Paget’s disease
abnormal bone remodelling due to increased ALP
normal Ca and PO4
usually elderly
describe bony metastases
high Ca and ALP, normal or high PO4
describe myeloma
Ca alone high
ALP usually normal
describe primary hyperparathyroidism
adenoma on parathyroid gland causing excess PTH high Ca (hypercalcaemia), ALP and low/normal PO4
define tumour markers
molecules which indicate the presence of a cancer or provide information of the likely future behaviour of a cancer
what are the use of tumour markers?
detect cancer in asymptomatic patients
differentiate between malignant and benign tumours
post-surgery to detect the amount that was removed
detect recurrence
predict how a tumour responds/has responded to treatment
what are the categories for the ideal tumour marker?
high PPV and NPV highly sensitive and specific inexpensive simple circulating level correlates with amount of tumour acceptable to subjects
describe some non-specific markers involved in detecting malignancy
hyponatraemia - indicates SIADH secondary to NSCLC
LDH - haematological malignancy
ALP - bony metastases, bone malignancy
total protein - multiple myeloma, Waldenstrom’s macroglobulinaemia
ferritin - renal cell carcinoma, leukaemia, hepatocellular carcinoma
define oncofetal antigens
present in cells in early development
reactivated in more undifferentiated cancer cells
describe 2 types of oncofetal antigens and what they look for
AFP - hepatocellular carcinoma, ovarian and testicular tumours
carcinoembryonic antigen - colorectal carcinoma
describe some hormones that are used as tumour markers
HCG - choriocarcinoma, testicular tumours, trophoblastic tumours
metanephrines - pheochromocytoma
calcitonin - medullary carcinoma of thyroid
IGF1 - pituitary malignancy
describe some glycoproteins that are used as tumour markers
CA19-9 - pancreatic tumours
CA125 - ovarian, breast, pancreatic and lung tumours
can be increased in benign conditions
describe some enzymes that are used as tumour markers
PSA - prostate cancer, other prostatic conditions
neurone-specific enolase - SCLC, neuroendocrine tumours
describe some cell components/antigens used as tumour markers
SCC antigen - gynae, head and neck and lung tumours
immunoglobulins - multiple myeloma
CEA - breast, pancreatic, ovarian, lung, stomach, colon and prostate cancer
what markers are produced by a multiple myeloma?
heavy and light immunoglobulin chains (detected as a paraprotein band)
Bence Jones protein (urine)
free light chains
beta-2 microglobulin (measures mass of tumour present)
what markers are produced by ovarian cancer?
CA125 inhibin HCG AFP carcinoembryonic antigen
what markers are produced by carcinoid tumours?
serotonin
S-hydroxytryptamine
catecholamines
chromogranin A
what are the causes of PSA increase?
prostate tumour BPH needle biopsy prostatitis urinary retention
rises occur rapidly and can take several days to return to normal
with what symptoms should CA125 be measured for ovarian cancer?
abdominal distension loss of appetite abdominal pain new onset irritable bowel syndrome >50
measured along with a pelvic US
what are the causes of CA125 increase?
ovarian, pancreatic, lung, breast, uterus, cervix and GI tract tumours
pancreatitis
peritonitis
hyperthyroidism
PID
ascites, HF, pleural effusion (fluid accumulation)
what patients should have an AFP test?
those known to have hep B and C-related cirrhosis
what are HCG and AFP used to detect?
non-seminoma type testicular germ cell tumours
follow-up to detect recurrence
what are HCG and LDH used to detect?
pure seminoma tumours
what are the causes of an AFP increase?
hepatocellular carcinoma ovarian tumour testicular tumour cirrhosis hepatitis ataxia telangiectasis pregnancy
what are the causes of a HCG increase?
pregnancy marijuana use choriocarcinoma trophoblastic tumour testicular tumour
what affects the reference range of CEA?
smoking other tumours IBD pancreatitis liver disease
what are the causes of CA19-9 increase?
pancreatic, colorectal, lung, liver and ovarian cancers
pneumonia
hepatobiliary disease
renal failure
name some examples of lipids
fats steroids fatty acids fat soluble vitamins (K, E and A) phospholipids
what are the functions of lipids?
maintain the structure of cell membranes
store energy
hormone synthesis
signalling
what are the functions of cholesterol?
hormone production (cortisol and sex hormone synthesis)
main component of cell membranes
vitamin D synthesis
bile acid synthesis (role in digestion)
what is the function of triglycerides?
efficiency way of storing and transferring energy
describe lipoproteins
required for lipid transportation in the circulation
contain apolipoproteins - made in the liver, bind to receptors, allow transportation
what is the function of chylomicrons?
transport triglycerides (mainly dietary)
what is the function of VLDL?
transport triglycerides from the liver to other tissues
what are the functions of apolipoproteins?
allow the transfer of different cholesterol fractions between different lipoprotein particles
co-factors for some of the enzymes used in cholesterol metabolism
bind to receptors in the cells
allow lipids to be taken up into cells
what are the pathways of lipid transport?
dietary
hepatic
tissue to liver (reverse cholesterol)
describe dietary lipid transport
mainly via chylomicrons
can go directly to cells if required (muscle, fat)
can go to liver to be processed and stored
describe hepatic lipid transport
the liver exports some of these stored triglycerides and moves them to the various tissues as required
the fraction that remain are transported back to the liver for further processing
describe reverse cholesterol transport
via HDL
cholesterol can go back to the liver and be removed from the circulation
doesn’t contribute to atheroma
what do apo A levels show?
the extent of reverse cholesterol transport
low - increased risk of atherosclerosis
what do apo B levels show?
an idea of the total number of atherogenic particles
high - increased risk of cardiovascular disease
what do lp a levels show?
genetic links
FHx of premature cardiovascular disease
describe Tangier’s disease
very low/absent alpha lipoprotein or apolipoprotein A
no mechanism for clearing cholesterol from the circulation
cholesterol deposited in tissues
enlarged orange tonsils (cholesterol deposits)
how is LDL cholesterol calculated?
friedewald-levy-fredrickson formula
= TC - HDL C - (TG/2.2) mol/L
not valid for very high triglycerides
describe atherogenic lipoprotein particles
LDL, IDL, VLDL, Lp a
= total cholesterol - HDL
what are the causes of increased LDL cholesterol?
hypothyroidism nephrotic syndrome ciclosporin cholestasis anorexia nervosa
what are the causes of decreased LDL cholesterol?
malabsorption
liver disease
malnutrition
what are the causes of increased HDL C?
exercise
moderate amounts of alcohol
oestrogen
what are the causes of decreased HDL C?
smoking metabolic syndrome T2DM malnutrition anabolic steroids systemically unwell
what are the causes of increased VDL C?
obesity diabetes hepatitis alcohol renal disease protease inhibitors retinoid acid-based treatments
describe familial hypercholesterolaemia
autosomal dominant associated with high coronary mortality 50% of men will have an MI <50 and 30% of women will have an MI <60 high lipid levels in children tendon xanthoma premature corneal arcus xanthelasma
problem with Apo B on the LDL particle or the LDL receptor on the cell
describe familial dysbetalipoproteinaemia
abnormality in the apo E receptors
apo E2 binds poorly to receptors and results in cholesterol not being removed as effectively from the circulation
1/170 are homozygous E2/E2
describe classical dyslipidaemia
cholesterol and triglycerides are numerically similar
increased cardiovascular risk
responds well to fibrates
which factors increase cardiovascular risk?
reduced eGFR known cardiovascular risk T1DM >40 FH mental health disorders inflammatory conditions (RA)
what is involved in the lifestyle management of dyslipidaemia?
fat should be <30% of calorie intake, saturated fat <7%
5x fruit and vegetable portions
high amount of whole green foods
2x fish/week, 1x oily
4-5x non-salted nuts or seeds/week
150mins moderate or 75mins vigorous intensity exercise
what is involved in the pharmacological management of dyslipidaemia?
primary prevention - atorvastatin 20mg
secondary prevention - atorvastatin 80mg
aim for >40% reduction in non-HDL cholesterol
fat soluble - simvastatin, atorvastatin
water soluble - pravastatin, fluvastatin, rosuvastatin
what are the causes of hypertriglyceridaemia?
obesity DM alcohol excess metabolic syndrome renal failure protease inhibitors isotretoin second generation antipsychotics (phenothiazines) primary dyslipidaemia
what are the consequences of hypertriglyceridaemia?
cardiovascular risk
raised cholesterol
pancreatitis
what is the management of hypertriglyceridaemia?
low fat diet (10% fat) diabetes control avoid alcohol fibrates statins fish oils
what is the treatment of combined dyslipidaemia?
statins 1st line
if triglycerides remain >5.6mmol/L then use fibrates
fish oils (omacor 4g/day)
describe BNP
produced by myocardial cells
released into the circulation in high concentration whenever myocardial cells are under stress or excess stretch
pro-BNP -> pre-pro-BNP
what are the consequences of increased BNP production?
promotes vasodilation
increased urinary Na retention, reducing the circulating blood volume
promotes myocyte growth
worse prognosis
how can heart failure be excluded?
if ECG and BNP are both normal
what can BNP be used for?
heart failure
LV failure following MI
assess prognosis in elderly, PE, general population
monitor treatment
what are the functions of the liver?
synthesis of proteins
detoxification (metabolism and elimination of waste)
metabolises proteins to ammonia
storage of glycogen and can replenish glucose when needed
describe bilirubin production
red blood cells are broken down into haem and globin
haem metabolised by haem oxygenase to produce iron and biliverdin
biliverdin is reduced by biliverdin reductase to produce bilirubin
describe bilirubin transport
initially binds to albumin (unconjugated) because it is insoluble and can’t pass into urine alone
describe hepatic uptake and conjugation of bilirubin
transported to hepatocytes
binds to ligandin
this allows it to be transferred to the endoplasmic reticulum and undergoes conjugation
via UPD glucuronosyltransferase
it becomes bilirubin diglucoronide (soluble)
describe excretion and enterohepatic recirculation of bilirubin
conjugated bilirubin goes into the bile via the gallbladder and bile duct
passes into the intestine
degraded by intestinal bacteria to urobilinogen (colourless)
passes through the intestine and is converted to stercobilin (brown)
exerted into faeces
some is bilirubin and urobilinogen is reabsorbed by the portal vein
passes back into the liver and goes into the systemic circulation
some urobilinogen passes through the kidneys (some becomes oxidised to urobilin (yellow)) and is excreted
what are the causes of unconjugated hyperbilirubinaemia?
haemolysis (along with raised AST, LDH and reticulocyte count and decreased haptoglobin)
problem with liver uptake of bilirubin from the circulation)
physiological neonatal jaundice (babies have an increased erythrocyte load and reduced ligandin)
gilbert syndrome (AD, reduced glucuronosyltransferase)
crigler-najaar syndrome (AR, two forms, more severe form of Gilbert syndrome)
describe the exocrine glands of the pancreas
allow digestive enzymes pass through a duct to the intestine trypsin chymotrypsin elastase lipase amylase
what happens when acidic fluid containing amino acids arise in the duodenum?
the small intestine produces cholecystokinin and secretin
what are the functions of cholecystokinin and secretin
causes gallbladder contraction
empties bile into the duodenum
allows digestion of fats
stimulate the production of alkaline fluid and pancreatic enzymes
describe some disorders of the exocrine pancreas
acute pancreatitis
pancreatic insufficiency (chronic pancreatitis, cystic fibrosis - chronic ongoing inflammation)
pancreatic cancer
what are the features of acute pancreatitis?
acute abdominal pain, relieved by leaning forward
shock, 3rd space fluid loss
acutely unwell
mortality 5-10%
amylase (pancreas and salivary glands)
lipase (more specific for pancreas)
CT - oedema and inflammation surrounding pancreas
what are the causes of acute pancreatitis?
gallstones ERCP hypertriglyceridaemia (fat obstruct pancreatic blood flow, >10mmol/L) alcohol excess viral drugs
what are the causes of raised amylase?
mumps calculi of salivary ducts CKD (reduced amylase excretion) duodenal ulcer perforation ruptured AAA DKA acute pancreatitis
what are associated with poor prognosis in acute pancreatitis?
increased age
increased LDH (cell breakdown)
increased urea (kidney dysfunction, multiple organ failure)
increased WCC
increased blood glucose
reduced albumin (negative acute phase reactant)
reduced Ca (auto-digestion of mesenteric fat)
what are the causes and features of pancreatic insufficiency?
removal of some necrotic areas of pancreas
chronic pancreatitis
cystic fibrosis
malabsorption (anaemia, weight loss, diarrhoea, steatorrhoea)
abdominal discomfort
osteomalacia
low Ca
low vitamin D
hyperglycaemic (check plasma glucose and HbA1c)
low faecal elastase (pancreatic dysfunction)
what tumour markers are associated with pancreatic cancer?
CEA
CA19-9
describe neuroendocrine pancreatic tumours
produce other hormones; insulin or glucagon
better prognosis
what are the purposes of therapeutic drug monitoring?
ensure that there are constant levels of the drug in plasma
avoid toxicity
identify non-compliance
name some drugs which require monitoring
lithium
vancomycin, aminoglycosides
cyclosporin, tacromilus, mycophenolate
digoxin
theophylline, caffeine (given in COPD and asthma)
anti-epileptics (phenytoin, phenobarbitone, carbamazepine, sodium valproate)
what tests are used to measure drugs?
clinical response (BP) INR/PT - warfarin renal function - ACEi, diuretics, NSAIDs potassium - spironolactone liver function - statins urinary protein - pencillamine, gold (for RA, can cause nephrotic syndrome)
what are the uses and complications of lithium?
treatment of bipolar disorder
diabetes insipidus
renal function
thyroid function
what are the complications of ahminoglycosides and vancomycin?
ototoxicity (auditory nerve)
nephrotoxicity
what are the complications of immunosuppressants?
nephrotoxicity
careful when used in immunosuppression of kidneys
how does paracetamol overdose occur?
converted to a toxic metabolite
usually inactivated by conjugation with glutathione
glutathione becomes depleted when an excess of paracetamol is taken
NABQI binds to sulphhydryl-containing groups on liver cell membranes, causing liver necrosis
what is the treatment of paracetamol overdose?
acetylcysteine
replaces glutathione and mops up toxic metabolite
most effective within the first 8hrs
measure INR and creatinine
what factors affect the metabolisation of paracetamol?
history of alcohol abuse
taking drugs that may induce liver enzymes (phenytoin)
what are the signs and symptoms of aspirin overdose?
vomiting sweating tinnitus blurred vision respiratory alkalosis (adults) metabolic acidosis renal failure
what is the management of aspirin overdose?
mild - oral fluids
vomiting - IV fluids
potassium monitoring, require supplements
oral activated charcoal (50g 4hrly)
alkalinisation (1L 1.26% NaCl over 2hrs, maintain urinary pH>7.5, allows salicylate to be excreted in the urine)
severe - haemodialysis (persistent acidosis, falling consciousness, levels >1000mg/L)
what are the features and management of ethanol excess?
depressed consciousness
hypoglycaemia (children)
fluids
monitoring
ensure airway is open in vomiting
glucose if required
what is the management of benzodiazepine and tricyclic antidepressant overdose?
benzodiazepines - flumazenil in respiratory depression
detection tests
do not provide the levels of drug (not useful in someone who’s already taking them)
monitoring
treat symptomatically
what are the symptoms and signs of lead poisoning?
abdominal pain
anaemia
bone marrow suppression
peripheral neuropathy (mononeuropathy)
what is the treatment of lead poisoning?
remove from source (occupational exposure)
chelation therapy (Ca EDTA or penicillamine)
monitoring of lead levels
what are the signs and symptoms of iron poisoning?
abdominal pain (gastric erosion)
nausea
hypotension
hepatic injury
what is the treatment of iron poisoning?
chelation therapy (desferrioxamine)
increases excretion
prevents toxic effects
monitoring
what is the pathology of methanol and ethylene glycol?
methanol produces formate and ethylene glycol produces glycolate
cause severe metabolic acidosis
liver and kidney toxicity
blindness
what is the treatment of methanol and ethylene glycol overdose?
ethanol
prevents metabolisation and formation of toxic metabolites
severe cases - haemodialysis
describe myoglobin
contains iron
provides an oxygen store
released into the blood during muscle damage
filtered by the glomerulus
what are the features of myoglobin excess?
damage and blockage of the renal tubules
AKI
brown/tea coloured urine (blockage of tubules)
CK increase
what are the muscle enzymes that are measured?
creatinine kinase
aspartate aminotransferase
lactate dehydrogenase
describe creatinine kinase
used in ATP regeneration
composed of 2 subunits (M or B)
main type in skeletal - CK-MM
main type in cardiac - CK-MB
what is the cause of high levels of CK-MB?
cardiac muscle damage
what are the causes of high levels of AST?
liver dysfunction
skeletal or cardiac muscle dysfunction
haemolysed sample
what are the causes of high levels of LDH?
increased cell breakdown or an increased number of cells
tumour growth - leukaemia and lymphoma
how is CK-MB affected by ischaemia?
rises after 4-9 hours
more cardiac-specific (can be affected by other muscle)
should return to baseline after 48-72 hours
second rise in CK-MB = second event
describe myalgia
muscle pain
no rise in CK
no severe muscle tenderness
describe myositis
mild increase in CK
increased muscle breakdown
describe rhabdomyolysis
rapid muscle breakdown CK increase (5-10x upper limit of normal)
what are the consequences of rhabdomyolysis?
increase in CK and myoglobin
monitor urea, creatinine, GFR (AKI)
increase in potassium phosphate (electrolyte release)
cardiac arrhythmias (K)
metabolic acidosis (AKI, organic acids released from muscle, ischaemia of muscle causing lactic acidosis
hypocalcaemia (falls initially then rises as muscles recover)
what are the causes of skeletal muscle disease (rhabdomyolysis)?
crush syndrome (excess alcohol) ischaemia seizure (rapid tonic-clonic muscle contraction) inflammation autoimmune disorders (polymyositis or dermatomyositis) hypothyroidism (mild increase in CK) hypo/hyperadrenalism hypo/hyperkalaemia, hypocalcaemia, hypohosphataemia, hypomagnesaemia statins (myalgia, not rhabdomyolysis) ecstasy, cocaine muscular dystrophies (CK increase) malignant hyperpyrexia fatty oxidation defects mitochondrial disorders paraneoplastic syndrome
describe the troponin complex
troponin C - binds to Ca, allows muscle contraction
troponin I - inhibitory
troponin T - anchors the tropomyosin complex
how are cardiac troponins affected by ischaemia?
large increase
put o 7 days to return to baseline
may be difficult to detect re-infarction
what are the causes of increased troponin levels?
ischaemia myocarditis (viral or autoimmune) post-cardiac surgery aortic dissection cardiomyopathy acutely unwell, cardiac strain (ICU) PE SAH stroke (other cerebral cause) CKD sepsis severe exertion (marathon
describe BNP
secreted by atrial and ventricular myocytes when the heart is under strain
cause natriuresis (loss of Na and water) and relaxation of smooth muscle
increase in acute/chronic heart failure, age, female
what are the uses of BNP?
diagnosing heart failure (rule out test)
screening for left ventricular function in those with IHD
risk stratification/prognosis
what action should be taken if a patient with a Hx of IHD presents with shortness of breath?
proceed to echocardiography (most likely due to HF)
what action should be taken if a patient presents with shortness of breath and no cardiac Hx?
measure BNP
if high, refer to echocardiography
what are the causes of an increase in BNP?
PE septic shock liver cirrhosis kidney injury COPD with cor pulmonale acutely ill from SAH or stroke AF IHD hyperthyroidism
how is water distributed in the body?
60% of the body weight is water
2/3s is intracellular fluid and 1/3 is extracellular fluid
of the extracellular fluid - 1/4 is in the vasculature, 3/4 is interstitial fluid
what is the main electrolyte present in intracellular fluid?
potassium
how is plasma Na regulated?
by the regulation of salt and water
volume receptors respond to changes in the intravascular volume via the kidneys
osmoreceptors respond to changes in the composition of plasma via thirst and water reabsorption
describe ANP
volume receptor in the left atrium
causes Na to be lost in the urine via natriuresis
reduces the amount of angiotensin and aldosterone, reducing the amount of Na reabsorbed
what is the impact of stretch receptors stimulating sympathetic activity when circulating volume falls?
increased renin secretion
angiotensin, aldosterone and sodium reabsorption
how do osmoreceptors regulate water?
thirst stimulation when osmolarity is increased
when osmolarity is increased, dehydration occurs and ADH is released from the posterior pituitary, preventing diuresis
what re the causes of a pseudo hyponatraemia?
hypertriglyceridaemia
hyperproteinaemia
what are the causes of Na movement into cells?
non-ketotic hyperosmolar coma
diabetic ketoacidosis
how does hyponatraemia cause symptoms?
water moves into cells
cerebral oedema
this results in nausea, headache, malaise, seizures, coma
what are the causes and features of hypervolaemic hyponatraemia?
congestive cardiac failure
cirrhosis
nephrotic syndrome
urinary Na <20 (without diuretics)
reduced albumin (cirrhosis and nephrotic syndrome)
increased urinary protein (nephrotic syndrome)
what are the causes and features of hypovolaemic hyponatraemia?
GI loss; diarrhoea, vomiting, fistula (low urinary Na)
renal loss; obstruction, (thiazide) diuretics, hyperglycaemia (high urinary Na)
skin turgor reduction, dry tongue, postural hypotension, tachycardia
what are the causes of euvolaemic hyponatraemia?
addison’s (synacthen test)
hypothyroidism
SIADH
describe SIADH
water retention when it is not necessary
plasma becomes diluted, plasma osmolarity falls and a concentrated urine is produced
high urinary Na
what re the causes of SIADH?
pain nausea carbamazpeine SSRI (sertraline, lustral) paraneoplastic syndrome (most commonly small cell carcinoma of the lung)
what is the management of hyponatraemia?
slowly corrected Na by 1-2 mmol/hr
not more than 12 mmol in 24hrs
faster - brain shrinkage and cerebral haemorrhage
treat underlying cause
Na depletion - oral or IV Na
SIADH - fluid restriction (1L/24hrs)
not responding/require Na correction rapidly - demeclocycline (causes nephrogenic diabetes insipidus, blocks ADH action)
aquaporin receptor antagonists - block Na reabsorption
what are the causes of hypovolaemic hypernatraemia?
dermal loss; burns, sweating, fever
GI loss; vomiting, diarrhoea, fistula
renal loss; diuresis (loop diuretics), AKI, CKD, PKD, hyperosmolar non-ketotic coma
what are the causes of hypervolaemic hypernatraemia?
iatrogenic
excess hypertonic saline administered
antibiotic infusions of a very high Na content
what are the causes of euvolaemic hypernatraemia?
diabetes insipidus (polyuria, polydipsia) fever (water loss in excess of salt) mechanical ventilation (insensible fluid loss in excess of Na)
describe diabetes insipidus
ADH deficiency; not enough being produced or posterior pituitary damage
what are the causes of diabetes insipidus?
tumour of pituitary
sarcoid (can infiltrate the pituitary)
ADH resistance (action blocked by the kidneys)
confirmation by water deprivation test (check urine, plasma osmolarity and fluid output)
what is the treatment of hypernatraemia?
treat the underlying cause
fluid replacement (hypovolaemic or euvolaemic)
correct Na 1-2 mmol/hr, 10-12 mmol/24hrs
