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Why monitor laboratory data?
Confirm diagnosis of condition e.g. glucose tolerance test in diabetes
Assess severity e.g. creatinine levels in renal failure
Check treatment response e.g. LFTs (Liver Function Tests) after treatment of acute hepatitis, FBC (Full Blood Count) after withdrawing a drug
Select appropriate drug or dose e.g. choice of diuretic in patient with electrolyte abnormalities, confirming lithium dose by therapeutic drug monitoring
Warning against contraindicated drugs e.g. use of nephrotoxic antibiotics in patients with severe renal failure
Ensures safety when using potentially dangerous drugs e.g. monitoring urea and electrolytes, monitoring INR for patients taking warfarin
Identifying disturbances caused by drugs e.g. side effects
Identifying asymptomatic imbalances e.g. non-obvious electrolyte disturbances
Differentiating between excess and deficiencies
Deciding appropriate route of treatment e.g. IV or oral
Corresponding with doctors - allows evidence-based clinical decision making
Reference ranges
Helps us decide whether a result is normal, high or low
These ranges are only a guide and vary between laboratories, hospitals and countries
Vary between adult, children, male, female
What is an important principle when treating an imbalanced lab value?
Always treat the underlying cause
May be drug-induced = remove / reduce drug
May be diet-induceded e.g. high cholesterol = modify diet accordingly
What electrolytes move in and out of the cells through the cell membrane?
Na+ out
K+ in
How do you monitor fluid balance?
Measure fluid input vs output using a fluid balance chart
Accounts for losses e.g. urine, vomiting, diarrhoea
Measure serum osmolality (concentration of electrolytes in the blood)
Sodium
Hypernatraemia
When do symptoms appear?
What are the symptoms?
Cause?
Treatment?
>150 mmol/L e.g. thirst, lethargy, irritability, headache, stupor
>170 mmol/L e.g. seizure, coma, death
Cause:
Loss of body water - e.g. dehydration, vomiting, diarrhoea, burns, diseases like diabetes insipidus, diabetic ketoacidosis
Gain of body sodium - drugs e.g. antacids, antibiotics, dispersible tablets, mineralocorticoid effects of steroids, lactulose, methyldopa, oestrogens
Treatment:
Depends on underlying cause:
Loss of body water - drink water, IV fluids e,g, 5% glucose if severe
Gain of body sodium - restrict sodium intake, diuretics
What is the key thing to remember with treatment of hypernatraemia?
Gradual correction
Too rapid a change in Na+ can cause complications e.g. cerebral oedema
Sodium
Hyponatraemia
When do symptoms appear?
What are the symptoms?
Cause?
Treatment?
Some patients are asymptomatic
If sympatomatic, symptoms manifest at around <130 mmol/L E.g. weakness, lethargy, headache, postural hypotension
Cause:
Loss of body sodium e.g.
Gastro-intestinal losses e.g. vomiting and diarrhoea
Salt losing kidney disorders
Addisons disease (adrenal insufficiency)
Gain of body water e.g.
Drugs e.g. ACEis, carbamazepine, lithium, NSAIDs, SSRIs
After surgery or injury
Renal disease causing reduced excretion
Congestive heart failure
Cirrhosis with ascities
Very young / old
Treatment:
Fluid restriction or slow sodium tablets for mild cases
Diuretic - in case of too much fluid
IV in severe cases (<120 mmol/L) or water intoxication - sodium chloride 0.9% or hypertonic saline
Potassium
K+ is key for…
Muscle excitability
So the main symptoms of K+ imbalances are related to the muscle and heart function
Potassium
Hyperkalaemia
Symptoms?
Cause?
Treatment?
Symptoms:
Excitability of muscle e.g. cardiac arrythmias, cardiac arrest, muscle weakness
Causes:
Drugs e.g. K+ sparing diuretics like Spironolactone, ACEis, ARs
Renal impairments
Metabolic acidosis
Tissue breakdown e.g. in surgery, trauma, severe infection
Treatment:
Ion exchange resins e.g. calcium resonium for mild-moderate cases
IV calcium gluconate to first stabilise the heart, then IV insulin, and salbutamol if needed for severe cases
Potassium
Hyperkalaemia
Why is IV insulin given as treatment in severe cases?
Draws K+ into the cells with glucose
Potassium
Hyperkalaemia
Why is hyperkalaemia considered a medical emergency?
Due to risk of cardiac death
Potassium
Hypokalaemia
Symptoms?
Cause?
Treatment?
Symptoms:
Muscle weakness, excessive fatigue, confusion, low blood pressure, cardiac arrhythmias
Causes:
Drugs e.g. diuretics such as furosemide and thiazides, salbutamol
GI losses
Renal impairment
Treatment:
Sando K effervescent tablets OR Kay-Cee-L solutionfor mild-moderate cases
IV mixed sodium chloride with potassium for severe case
Calcium
Hypercalcaemia
Symptoms?
Cause?
Treatment?
Symptoms: Muscle weakness, anorexia, constipation, fatigue, headache, psychosis, arrythmias, coma, death
Causes:
Hyperparathyroidism, renal disease
Cancer
Excessive vitamin D doses
Bone disease e.g. Paget’s
Treatment:
Increase fluid intake
By mouth if mild
By IV sodium chloride 0.9% to promote calcium diuresis if severe
Calcium
Hypocalcaemia
Symptoms?
Cause?
Treatment?
Symptoms:
Neuromuscular excitability e.g. cramps, parasthesia, tetany, convulsions at levels <1.6 mmol/L
Causes:
Hypoparathyroidism, renal disease
Vitamin D deficiency
Excessive phosphate administration
Treatment:
Oral calcium tablets
IV calcium gluconate if acute tetany is present
Phosphate
Hyperphosphataemia
Symptoms?
Cause?
Treatment?
No symptoms
Causes:
Kidney damage e.g. in renal failure
Cell damage where phosphate is released from inside the cells
Drugs e.g. calcium, excessive vitamin D, bisphosphonates
Treatment:
Reduce phosphate intake moderately
Phosphate binding salts e.g. calcium, aluminium
Phosphate
Hypophosphataemia
Symptoms?
Cause?
Treatment?
Symptoms:
muscle weakness, rhabdomyolysis, cardiac and respiratory problems, osteomalacia, rickets
confusion, seizures, coma
Causes:
Drugs e.g. antacids which impair phosphate absorption
Malnutrition
Alcoholism
Re-feeding syndrome
Treatment:
Oral phosphate in mild cases
IV potassium phosphate infusion in severe cases
Magnesium
High magnesium
Symptoms?
Cause?
Treatment?
Symptoms:
Muscle weakness, CNS and respiratory depression
Cardiac problems e.g. cardiac arrest, slow heart beat
Nausea + vomiting
Causes:
Drugs e.g. laxatives or antacids which contain magnesium » especially in patients with renal impairment as cannot clear magnesium
Treatment:
Fluids (sometimes with added furosemide) » promotes renal clearance of Mg
Haemodialysis if patient has renal impairment
IV calcium gluconate for treatment of cardiac and respiratory symptoms in severe cases
Magnesium
Low magnesium
Symptoms?
Cause?
Treatment?
Symptoms: muscle weakness, contractions, tetany, tremor, convulsions
Causes:
Drugs e.g. diuretics, aminoglycosides
Alcohol
Renal impairment or GI issues e.g. chronic diarrhoea
Treatment:
Oral Mg supplements in mild cases
IV Mg in severe cases
Mg rich foods e.g. bananas, spinach, wheat, nuts, artichokes
What underlying problems do high urea levels indicate?
Renal failure - kidneys cant clear urea effectively
Catabolic states where the body is breaking down tissue e.g. fever, starvation, surgery
GI bleeding - digestive blood is broken down into protein which raises urea levels
High protein diet - urea is a byproduct of protein metabolism
Dehydration - reduced kidney perfusion leads to increased urea levels
What underlying problems does high creatinine indicate?
Renal failure
Reduced renal perfusion e.g. due to fall in BP, heart failure, fluid loss
Drug induced e.g. cimetidine, co-trimoxazole, salicylates
Liver function tests
Not specific to liver disease alone
Influenced by many factors outside the liver
Not reliable indicators of liver function
If a single LFT is abnormal - other tests needed to confirm
If multiple LFTs are abnormal - liver disease is almost certain - but other tests needed to know exactly what is wrong with the liver
Useful to monitor acute liver recovery e.g. after hepatitis or drug induced liver damage
Liver Function Tests (LFTs)
Bilirubin
Symptoms
Causes
Symptoms:
35 - 50 micromol/L - jaundice
>350 - 500 micromol/L - severe jaundice
Causes:
Haemolysis - increased breakdown of RBCs
Hepatocellular damage - liver cannot process bilirubin effectively e.g. in hepatitis or drug induced liver injury
Cholestasis (aka obstructive jaundice) - where bile flow is blocked e.g. gall stones or tumours
Liver Function Tests (LFTs)
Alkaline Phosphatase (ALP)
Where is it found?
Causes of raised ALP?
Found in most tissues, especially: liver, bile duct, placenta, bone
This means ALP levels are not specific to the liver and can indicate damage in other parts of the body e.g. bone disease, pregnancy
So should check other markers if a raised ALP is seen
Causes of raised ALP:
Damaged or inflamed tissue e.g. liver disorders, renal failure, bone disease, cancer
Pregnancy
Liver Function Tests (LFTs)
Transaminases (AST and ALT)
What does AST:ALT ratio indicate?
What do high levels of AST and ALT mean?
AST : ALT ratio indicates underlying cause
In alcohol related liver disease - AST:ALT is 2:1
High levels of AST and ALT less than 5 times the normal amount = alcohol abuse, hepatitis, cirrhosis
High levels of AST and ALT more than 5 times the normal amount = seen across a wide range of liver disease so less useful
The key markers of hepatocellular injury are…
The transaminases (AST and ALT)
Liver Function Tests (LFTs)
Gamma-glutamyl transferase (GGT)
Causes of high GGT
Not specific to the liver
Elevated levels can indicate a variety of conditions
Causes of high GGT:
Alcohol abuse
Liver disease
COPD
Myocardial infarction
Cancer
Enzyme inducers e.g. barbiturates
Raised ALP + GGT =
Indicates a hepatic condition rather than a bone condition
Liver Function Tests (LFTs)
Prothrombin Time (PT)
What does this reflect?
What does PT depend on?
Factors effecting PT
Treatment?
Reflects blood clotting
Prothrombin time depends on vitamin K clotting factors » synthesised in the liver so liver condition is imported
Factors effective PT:
Chronic biliary tract disorder causing vitamin K deficiency
Liver cell damage - reduced synthesis of clotting factors
Treatment:
Water soluble vitamin K (menadiol)
Liver Function Tests (LFTs)
Plasma proteins
Main plasma protein
What does it indicate
When do low albumin levels occur?
Albumin
Long half life (around 20 days) - so reflects chronic hepatic impairment rather than acute
Low albumin levels occur in chronic liver disease
Red Blood Cell Conditions
Anaemia
What is anaemia?
Is anaemia a diagnosis?
How is it interpreted?
Physical symptoms of ALL anaemias?
Causes?
Reduced Hb level
Not a diagnosis, but a sign of an underlying issue
Should be interpreted in the context of a full profile of blood tests, not just the Hb level alone
Physical symptoms of ALL anaemias:
Fatigue, breathlessness, dizziness, headache
Pallor of the skin and mucus membranes seen on examination
Heart irregularities e.g. palpitations, murmurs
Causes:
Malabsorption e.g. due to alcoholism
Increased demands e.g. pregnancy
Red Blood Cell Conditions
Anaemia
Measurements which indicate iron deficiency anaemia
Low serum Hb
Low ferritin iron
High iron binding capacity » body trying to maximise iron
Red Blood Cell Conditions
Anaemia
Which drugs can induce iron deficiency anaemia?
NSAIDs - can cause GI bleeds
Red Blood Cell Conditions
Anaemia
Treatment of iron deficiency anaemia
Oral iron - 100 - 200mg of elemental iron/day, continue for 3 months after Hb normalises
Note: Different irons salts deliver different amounts of iron
White Blood Cell Disorders
Neutropenia
What is it?
What is unusual about blood tests in patients with neutropenia?
Symptoms?
Causes?
Reduction of neutrophils - increases risk of infection
Most other blood tests including Hb appear normal
Symptoms: infections, fever, chills
Causes: drugs e.g. cytotoxics, infections
Treatment: stopping the causative drug, treating the infection, growth factors in severe cases
Platelets
Thrombocytopenia
What is it?
Symptoms?
Causes?
Reduced thrombocytes - essential for clot formation
Symptoms:
Possible anaemia due to prolonged bleeding time
Bleeding into the skin
Nose bleeds
GI bleeding
Causes:
Destruction of platelets in autoimmune conditions
Certain drugs