Clinical biochemistry (year 2) Flashcards
what is the role of diagnostic tests?
to conform/refute a clinical hypothesis so shouldn’t be carried out blind
what must be done before taking blood?
history
physical exam
identify clinical problems
differential diagnosis
what are the two types of tests?
screening
confirmation
what samples can be taken?
urine, blood, faeces, cavitary fluid, synovial fluid, CSF
define clinical biochemistry
analysis of samples of bodily fluid
what is plasma?
extracellular fluids plus additional proteins
what are the functions of plasma?
transport - nutrients, hormones, metabolites
clotting
osmolarity maintenance
oncotic pressure maintenance
what is the difference between whole blood and plasma?
plasma doesn’t have any cells
what is the main difference between the collection of plasma and serum?
serum is allowed to clot so doesn’t contain clotting factors
plasma still contains coagulation factors by using an anticoagulant
what is chemicals is blood placed in to prevent clotting to obtain plasma?
lithium heparin
sodium citrate
when measuring glucose in plasma/serum what tube is blood collected into?
NaFluoride/oxalate or NaFluoride/EDTA tube
what colour are NaFluoride/oxalate or NaFluoride/EDTA tubes?
grey top
what does fluoride inhibit?
glycolysis - so glucose isn’t used up and can be measured
why may a decrease in concentration of analytes in serum occur?
decreased input
increased output
why might input be decreased causing a decrease in concentration of serum analytes?
decrease synthesis, nutritional deficiency, poor absorption, lack of precursors
why might input be increased causing a decrease in concentration of serum analytes?
excessive demand, increased excretion, pathological loss
why may an increase in concentration of analytes in serum occur?
increased input
decreased output
some changes to plasma analytes can be relative, what does this mean?
changes caused by increased/decreased water - haemoconcentration
what is the reference interval?
range of values encompassing 95% of a tested population of apparently healthy animals
why is 95% used as a reference interval instead of 100%?
maximise detection of diseased animals
what is the term used for decreased albumin in serum?
hypoalbuminaemia
what are pre-analytical errors?
errors that happen before test is carried out
what are some common pre-analytical errors?
labelling, anticoagulation, contamination, improper handling, inappropriate storage
what may an abnormal increase in potassium during blood sampling be due to?
EDTA contamination
what is accuracy?
how close the result is to the true value
what is precision?
reproducibility of the laboratory methods
what is sensitivity?
likelihood of a positive result when disease is present
what is specificity?
likelihood of a negative result when disease is absent
what is a positive predictive value?
likelihood that a patient with a positive result has the disease
what is a negative predictive value?
likelihood that a patient with a negative result does not have the disease
what are the proteins measured in total protein?
albumin
globulins (include clotting factors)
how can total protein be measured?
refractometry
biuret method
where is albumin produced?
hepatocytes
where is albumin catabolised?
most tissues
what is the function of albumin?
carrier protein
role in oncotic pressure
what is albumin a carrier protein for?
unconjugated bilirubin bile acid free-fatty acid drugs hormones calcium
where are globulins produced?
B lymphocytes
plasma cells
liver
what does serum protein electrophoresis separate proteins based on?
size of molecule
electrical charge
what is increased levels of albumin called?
hyperalbuminaemia
hyperalbuminaemia is usually only relative, what does this mean?
body doesn’t overproduce albumin
what may be a causes of hyperalbuminaemia?
dehydration
what may hyperalbuminaemia be accompanied by?
increased PCV
azotaemia
increase of all proteins
what is increased levels of globulins called?
hyperglobulinaemia
what could cause hyperglobulinaemia?
dehydration
inflammation
how is hyperglobulinaemia characterised by electrophoresis?
monoclonal or polyclonal
what is monoclonal hyperglobulinaemia?
production of a single type of immunoglobulin usually due to neoplasia
what is the most common neoplasia that causes monoclonal hyperglobulinaemia?
multiple myeloma
what are the types of protein associated with inflammation? (3)
positive acute-phase
negative acute phase
delayer response
what are some examples of positive acute phase proteins?
haptoglobin
fibrinogen
what are some examples of negative acute phase proteins?
albumin
transferrin
what are some examples of delayed response proteins?
complement
immunoglobulin
what do positive acute phase proteins do during inflammation?
increase in number
what do negative acute phase proteins do during inflammation?
decrease in number
are acute phase proteins specific?
no (non-specific)
what are acute phase proteins under the influence of?
cytokines
what do rapid reacting acute phase proteins do?
increase within 24 hours then decrease rapidly after the insult is removed
what are some examples of rapid reacting acute phase proteins?
serum amyloid A
C reactive protein
what are some examples of late reacting acute phase proteins?
haptoglobin
fibrinogen
what are the causes of hyperfibrinogenaemia?
inflammation
dehydration
how can hyperfibrinogenaemia be measured?
heat precipitation
coagulation assay
what may cause hypofibrinogenaemia?
decreased synthesis from liver increased consumption (fibrinogeneolysis)
what tests can be effected by decreased fibrinogen production?
fibrinogen concentration
PT
PTT
TP
what is the term used if all proteins are low?
panhypoproteinaemia
what could cause panhypoproteinaemia?
acute haemorrhage
GI loss
what are some causes of hypoaluminaemia due to decreased production?
chronic liver disease
prolonged malnutrition
maldigestion/malabsorption
what are some causes of hypoaluminaemia due to increased loss?
kidney-glomerular leakage
GI loss
burns
when is hypoglobulinaemia seen?
failure of passive transfer in neonates
combine immunodeficiency in foals
what are cholesterol and triglyceride required to be incorporated with to be transported in blood?
into a soluble lipid-protein complex (lipoprotein)
what are the types of lipoproteins?
chylomicrons
very low density lipoprotein
low density lipoprotein
high density lipoprotein
what do chylomicrons deliver to cells?
dietary triglycerides
what do very low density lipoproteins deliver to cells?
triglycerides made by the liver
what do low density lipoproteins deliver to cells?
cholesterol
what do high density lipoproteins do?
pick up tissue cholesterol for elimination in bile
what lipids are tested for in blood?
total cholesterol and triglycerides
what is lipaemia primarily caused by?
increased chylomicrons
increased VLDLs
what does plasma look like during lipaemia?
opaque plasma
what artefacts can be caused by lipaemia?
enhanced tendency to haemolysis falsely high haemoglobin falsely high TP unreliable fructosamine low sodium
what is requires when measuring triglycerides?
the animal has fasted
what may cause hypercholesterolaemia?
endocrine disease hepatic disease steroid administration diet nephrotic syndrome
why may enzyme activity be increased? (5)
cell damage impaired enzyme clearance physiological induction artifactual
what are typical diagnostic uses of enzyme activity in serum? (3)
hepatocyte damage
exocrine pancreas damage
myocyte damage
why may enzymes leak from myocytes? (3)
degradation
necrosis
inflammation
what are enzymes of muscles that can be measured?
creatine kinase (CK) aspartate aminotransferase (AST) lactate dehydrogenase (LDH)
what is the most tissue specific enzyme of muscle that can be measured?
creatine kinase (CK)
what is the function of creatine kinase?
make ATP available for muscle contraction
what is creatinine?
waste product from the spontaneous breakdown of creatine
what is creatinine used to assess?
kidney function
where in the cell in creatine kinase found?
cytoplasm
where else (other than skeletal muscle) is creatine kinase found?
brain (CSF)
is creatine kinase sensitive and specific?
yes (rapid increase/decrease)
what is the degree of increase of creatine kinase proportional to?
degree of muscle damage
what could a small increase in creatine kinase be due to?
IM injections
traumatic venupuncture
what does persistent increase of creatine kinase mean?
ongoing muscle damage
what are some causes of muscle injury?
degenerative (hypoxia) metabolic neoplasia nutritional inflammatory toxic trauma
what can interfere with creatine kinase levels, causing an artifictual increase?
haemolyiss (releases other enzymes)
hyperbilirubinaemia
what enzymes are used to identify injury to pancreatic cells? (2)
amylase
lipase
what is the most common reason for increase in amylase and lipase?
inflammation (pancreatitis)
what enzymes can be used to assess liver function?
alanine aminotransferase (ALT) aspartate aminotransferase (AST) lactic dehydrogenase (LDH) sorbitol dehydrogenase (SDH) glutamate dehydrogenase (GLDH)
where is ALT found?
mainly liver
some in muscle
what animals is ALT mainly used in?
small
where is AST and LDH found?
liver
muscle
where is SDH and GLDH found?
liver specific
what animals is GLDH mainly used in?
large
what are the liver leakage enzyme that are measured not correlative of? (3)
reversibility of injury
hepatic function
prognosis
what is cholestasis?
stopping of the flow of bile
what enzymes can be used to assess cholestasis? (cholestatic liver enzyme)
ALP (alkaline phosphatase)
GGT (gammaglutamil transferase)
what is the major measurable isoform of ALP?
liver-ALP
during cholestasis what happens to the concentration of ALP?
increases
where is liver-ALP found?
bound to plasma membrane of hepatocytes and biliary epithelium
what does an increase in GGT indicate?
cholestasis
what species is GGT a more sensitive measure of cholestasis?
cats
horses
cattle
what may lead to decreased bile flow/excretion?
intrahepatic - hepatocellular swelling
extrahepatic - bile duct obstruction
functional
what are the markers of cholestasis?
bilerubin
bile acids
cholesterol
cholestatic enzymes
in horses why may be see hyperbilirubinaemia?
due to fasting/starving
what are the clinical signs of hyperbilirubinaemia?
jaundice
bilirubinaemia
what could cause hyperbilirubinaemia? (4)
cholestasis
haemolytic anaemia
reduced hepatocellular function
fast/starving in horses
what functions of the liver can be testing in clinical biochemistry?
uptake/excretion of bilirubin/bile acids
ammonia to urea conversion
synthesis of metabolites
immunological function
what functions would be decreased if there was alterations of hepatic blood flow?
uptake/excretion of bile acids
ammonia to urea conversion
immunological function
what are the major sources of glucose? (2)
dietary absorption
liver production
what are the processes that produce glucose in the liver?
glycogenolysis
gluconeogenesis
what promotes the process of glycogenolysis?
catecholamines
glucagon
what promotes the process of gluconeogenesis?
corticosteroids
glycogen
growth hormone
what regulates glucose metabolism?
absorption
insulin production
insulin antagonists
what is the best tube for collecting a glucose sample into if it is being sent off for analysis?
fluoride oxalate
what is a common cause of transient hyperglycaemia?
adrenalin (fear/excitement)
what are the causes of hypoglycaemia? (5)
excessive use reduced hepatic storage insufficient diet excessive insulin/analogues lack of corticosteroid
what could cause excessive use of glucose?
sepsis
neoplasia
excessive physical exertion
what are common causes of hyperglycaemia? (5)
after a meal cathecolamines iatrogenic (exogenous glucose administration) insulin antagonism diabetes mellitus
is glucose normally present in urine?
no (reabsorbed in proximal tubules)
what is glucose in urine called?
glucosuria
what does glucosuria usually mean in dogs?
diabetes mellitus
other than glucose concentration, what else can be measure to confirm diabetes?
glycated proteins
how are glycated proteins formed?
glucose slowly reacts with amino acid groups on all proteins
what is the rate of reaction of glycated protein formation dependant on?
blood glucose concentration
what is the glycated protein measured in animals?
fructosamine
what is fructosamine?
irreversibly glycated albumin
what will be the difference in fructosamine of a diabetic and stressed cat?
diabetic - high
stress - low
what electrolytes are mainly present extracellularly?
sodium
chloride
bicarbonate
what mechanisms control sodium concentration? (3)
thirst
RAAS
ADH
what ways can alter sodium concentration?
loss of sodium/water
loss of just water
what are the overall causes of hyponatraemia? (2)
loss of sodium
water retention
what are some causes of loss of sodium rich fluids?
vomiting/diarrhoea
kidney
skin (burns/sweat)
what is the most common cause of hypernatraemia?
water loss in excess of sodium
what could cause water loss in excess of sodium?
fever/panting
lack of ADH
inadequate water intake
osmotic diuresis
what is high blood sodium called?
hypernatraemia
what does chloride follow?
sodium (increase/decrease together)
what is a causes of chloride increasing/decreasing without sodium?
vomiting pure stomach continents (HCl)
what effect does aldosterone have on potassium?
increases excretion
what could cause hyperkalaemia?
increased intake
reduced renal excretion
movement out of cell
what could cause hypokalaemia?
reduced intake
renal losses
GI losses
movement into cells
what can cause potassium to move out of a cell?
acidosis
lack of insulin
what can cause potassium to move into a cell?
alkalosis
insulin
what regulates calcium and phosphorus? (3)
parathyroid hormone
vitamin D3
calcitonin
what effect does increased parathyroid hormone have on calcium and phosphorus?
hypercalcaemia
hypophosphataemia
what else other than the parathyroid can release parathyroid hormone related protein?
tumours of some organs
what is parathyroid hormone opposed by?
calcitonin
where is calcitonin secreted?
thyroid C-cells
what are the byproducts of nitrogen metabolism used as markers of renal function? (2)
urea
creatinine
what is a nephron?
functional unit of the kidney formed from glomerulus, bowman capsule and collecting duct
where is urea made?
liver
what group of animals is urea not used as a measure of GFR?
ruminants
why is urea not used to measure GFR in ruminants?
because the excrete some in saliva and its degrades in rumen
where is creatinine produced?
muscle
how is creatinine produced?
degradation of muscle (proportional to muscle mass)
is creatinine or urea reabsorbed in the kidney?
creatinine - no reabsorption
urea - reabsorption
what is uraemia?
clinical syndrome resulting from loss of kidney function
are all uraemic patients azotaemic?
yes
are all azotaemic patients uraemic?
no
what is azotaemia?
increased creatinine/urea
what could be the cause of increased urea?
decreased GFR
GI haemorrhage
high protein diet
recent meal
what could be the cause of decreased urea?
reduced production
low protein diet
what could be the cause of increased creatinine?
decreased GFR
high muscle mass
what could be the cause of decreased creatinine?
low muscle mass
what is prerenal azotaemia due to?
dehydration
decreased CO
increased production
what is postrenal azotaemia due to?
urine leakage/blockage
how can prerenal azotaemia be differentiated from other azotaemia?
high urine concentration
dehydration/hypovolaemia signs
responds to fluid therapy
how can azotaemia be differentiated from other azotaemia?
low urine concentration
no response to fluid therapy
how can postrenal azotaemia be differentiated from other azotaemia?
clinical evidence (eg. hyperkalaemia)
what are the renal influences on urine specific gravity? (3)
number of functional nephrons
tubular function
hydration status
what are the extra renal influences of urine specific gravity?
ADH release/action medullary concentration gradient osmotic forces drug therapy behaviour
why must urine be analysed rapidly after sampling? (5)
cells disintegrate pH rises (carbon dioxide evaporates) crystals form bilirubin/urobilinogen breakdown bacteria grow/die
what could a red coloured urine be due to? (3)
haematuria
haemoglobinuria
myoglobinuria
what could a dark yellow/brown coloured urine be due to?
bilirubinuria
how is haematuria and pigmenturia differentiated? (2)
haematuria contains erythrocytes in the sediment
colour doesn’t clear with centrifugation in pigmenturia
how can myoglobinuria and haemoglobinuria be differentiated?
myoglobin - urine red but plasma clear
haemoglobinuria - urine red and plasma red
what could cloudy urine be due to?
mucus bacteria lipids sperm salts increased cellular eliments crystalluria
what is used to measure urine specific gravity?
refractometer
what is specific gravity?
measure total solute concentration of urine (weight compared to distilled water)
what is urine specific gravity used for?
confirm polyuria
evaluate kidney concentrating ability
differentiating renal and pre-renal azotaemia
what is the most common cause of protein in urine?
pyuria
what could be the cause of ketones in urine?
diabetes
negative energy balance
what is the most common urinary crystals seen?
struvite (alkaline urine)