Advantages over Urine MC+S

Urine Microscopy, Culture and Sensitivities (MC+S) is the ideal urine test. But it requires sending a sample to the lab, and culture results can take several days. Urine dipstick testing on the other hand is:

• Simple
• Quick
• Cheap

Disadvantages

• Not precise

You should only perform a urine dipstick after a full history and thorough examination!

Indications

• Diabetes Mellitus – polydipsia, polyuria, weight loss, fatigue, infection, DKA
• UTI – dysuria, frequency, back pain, haematuria
• Pregnancy – for monitoring purposes; pre-eclampsia
• Renal and CVD – hypertension, oedema, renal colic (for blood), suspected heart failure
• Drugs – gold, penicillamine, recreational
• Others – anxiety, hysterical polydipsia

Procedure

Urine dipstick samples are usually self collected by patients. Ideally it should be a mid-stream urine sample (MSU) – this reduces the risk of contamination from the normal bacterial skin flora. You should explain to your patient how to collect the sample:

• Don’t open the bottle until you are ready to take the sample – it should be sterile inside the container – taking the lid off and leaving it open to the air can increase the risk of ocntamination
• The amount of urine is not that important. Tell patients they don’t have to completely fill the bottle!
• The sample should be tested within 2 hours. If this is not possible, you may be able to preserve the sample to some extent by keeping in the fridge

Testing a Urine Sample – The Procedure

1. Wash hands, put on gloves
2. Look at the sample pot – check it is the correct patient and the correct date. You also want to know if it was taken in the last 2 hours – a crude way to know if it is recent is to check if it is warm!
3. Look in the bottle – are there any precipitations?
   1. Does it look a normal colour?
   2. Normal – straw yellow
   3. Dark – bile pigments may be present due to dehydration
   4. Red – haematuria, menstrual blood?, food; e.g. beetroot and blackberries
   5. Green/blue – Pseudomonal UTI, triamterene (this is a potassium sparing diuretic), asparagus
   6. Orange – dehydration (bile pigments), phenothiazines, high intake of carrots
   7. Clarity – how clear is the sample?
   8. Cloudy – can be normal (especially in males), may also be bacterial infection (check the smell), WBC, lipids
   9. Frothy – this suggests proteinurea
   10. Is there anything in there that shouldn’t be in there?
   11. Make sure you keep the bottle on the tray, or trolley that it is given to you on! – e.g. in OSCE’s don’t lift it up and put it on the table!
4. Open it and have a smell
   1. Ketones – smell like nail polish remover – diabetes
   2. Sweet smelling – remember the renal threshold – some people naturally excrete glucose in their urine. Other wise could be a sign of DM
   3. Foul smelling – bacterial infection, GI-bladder fistula
5. Check your dipsticks:
   1. Are they in-date?
   2. Check silica gel crystals are present in the container to ensure the sticks have been kept dry
6. Dip it – stick the stick all the way in, ensure all of the test areas have been in contact with the urine. Shake off the excess, and perhaps dab it on a paper towel.
7. Wait the required amount of time (different test patches require a different wait time) and note down the results. The time required for each inidivdual test is usually listed on urine diptick container – for example, leucocytes often require a 2 minute wait. The times down the side of the bottle are the time from 0, not the time between each result.
8. Compare the strips to the colours on the reference sticker
9. If in your exam – explain what irregularities are present, and what would you do to test them further
10. Put the lid back on, put the sample back. Take gloves off (yellow bin) and wash your hands.

 Example of a Urine Dipstick chart

Abnormal urine dipstick findings

Haematuria

• Contamination from menstrual bleeding ≪ this is THE most common cause of ‘haematuria’!
• Recent trauma
• Prostate examination
• Other recent urological examination (e.g. cystoscopy)
• Glomerular or tubular pathology
• Urologic pathology – this present with haematuria without proteinuria
• Exercise induced – long distance runner. Result will be negative if repeated after 72 hours with no further exercise
• Dehydration
• Urine dipstick test is 90% sensitive, but less specific. However, only 0.5-6% of patients have significant underlying pathology

Proteinuria

• Healthy adults excrete 80-120mg protein / day. This can be up to 1g per day.This usually occurs at night. This is generally too small of an amount to be detected on urine dipstick testing. The dipstick can detect 20-30mg / dl.
• Proteinuria above normal levels on a urine dipstick may indicate; renovascular, glomerular or tubular interstitial renal disease, or it can be a sign of diseases that cause overproduction of urine, such as myeloma.
• False negatives can occur when there is very diluted urine and / or when the primary protein is not albumin. They can also occur in very alkaline conditions.
• Transient proteinuria – in young patients this is usually not a problem, and resolves within a few days, or after >8 hours lying down.  In older patients it may be a sign of congestive heart failure.
• Intermittent proteinuria – can be present in young adults as a result of prolonged vertical posture, exposure to cold, pregnancy and hypertension. This usually produces about 1g of protein per day. This is asymptomatic, and should only ever be treated in renal problems are detected.
• Persistent – due to underlying disease, most commonly; glomerular. This often produces in excess of 2g protein per day. Can also be due to overflow proteinuria (myeloma), connective tissue disorders, DM, hypertension.
• Pre-eclampsia  – a condition in pregnant women characterised by hypertension and proteinuria.

Summary of causes of proteinuria

• Renal diseases
  • CKD
  • Pre-eclampsia (pregnancy)
  • Glomerulonephritis
  • Diabetes
• Drugs
  • NSAIDs
• UTI
• Vaginal discharge
• High protein diet
• High level of exercise in last 24 hours
• Dehydration
• CCF (Heart failure)
• Emotional stress
• Most acute illnesses and infections!

Glycosuria         

• Small amounts of urine are naturally excreted. The actual amount varies with the renal threshold from patient to patient. Generally these levels are too small to be detected on urine dipstick.
• Can be caused by diabetes, Cushing’s syndrome, liver and pancreatic disease, Fanconi’s syndrome

Ketones

• Diabetic ketoacidosis, pregnancy, after starvation and dehydration (often present in gastroenteritis / dehydration), rapid weight loss

Bilirubin and urobilogen

• Normal urine contains no bilirubin, and very little urobilogen
• Conjugated bilirubin may appear in the urine in the presence of liver disease, or bile duct obstruction.

Leukocytes

• This test has lower specificity for infection than nitrites, and thus testing for nitrites is seen as for the presence of infection.
• Be wary of diagnosing a UTI based of leucocytes only. In my practice (as a GP) in a well, asymptomatic patient I will often send these samples for MC+S without treating, to confirm if a UTI is present.
• However, especially in the elderly, leucocytes only may indicate a UTI

pH

• Should be between 4.5 and 5.3
• A metabolic acidosis and alkaloid urine suggests a renal tubular acidosis. These patients have a risk of stone formation and nephrocalcinosis
• Acidic urine can be caused by diet and uric acid calculi
• Note that stale urine can become alkaline – thus you should check if the urine has been left fro any period of time

Nitrites

• The presence of nitrites is essentially diagnostic for UTI
• Nitrites are produced by bacteria; and thus raised levels indicate the presence of bacteria in the urine. Accuracy may be affected in symptomatic patients, and patients on antibiotics.
  • Urine should usually be sterile
  • Patients with catheters often have

Specific gravity

• This shows the concentration of solutes in the urine; and is thus a measure of the ability of the kidneys to concentrate fluids.
• If the value is high:
  • Dehydration
  • Glycosuria
  • Proteinuria
  • Renal artery stenosis
• If the value is low
  • Excess fluid intake
  • Renal failure
  • Pyelonephritis
  • Diabetes insipidus

Finishing off

• Consider FBC and U+E’s if there is any proteinuria, abnormal specific gravity
• If glucose is present; do a random/fasting blood glucose, or a glucose tolerance test, or HbA1c. Refer onto diabetes specialist if required.
• If protein is present; rule out benign causes (e.g. the postural cause, you could do an early morning urine sample, or you could to a 24hr glucose monitoring. Refer to renal specialist
• If blood is present; send the urine sample to microscopy, refer to renal/oncology/urology
• Bacteria; send for microbiology, culture and sensitivity (MC+S), and if symptoms present, then start on broad spectrum antibiotics. UTIs are most commonly cause by E. coli. Trimethoprim or nitrofurantoin are common first line choices for antibiotics – but check your local guidelines.

24 hour urine sampling

Indications

• Volume –  water overload / depletion
• total protein excretion – glomerular function
• creatinine clearance – renal function
• Cortisol – Cushings
• Na/K – renal failure, aldosteronism / Conn’s syndrome
• Catecholamines – phenochromocytoma

Procedure

• Pick a start time, e.g. 9am. The patient should completely empty their bladder before they start
• After this time, they should collect all their urine. They are often given two containers; a small one to urinate in and a larger one to collect it all in
• If possible, urine should be kept refrigerated
• at the end of the 24hrs, the patient should urinate and collect it one last time, before taking the sample for analysis as soon as possible

Results

• Volume – normal production is about a minimum of 30ml/hour. In a 24 hour period you should be worried if the total volume is less than 500-600ml (technically 720ml/day is normal ‘minimum’)
• Protein
  • <2.0g – may indicate tubulointerstitial problems
  • 2.0-3.0g – this is considered in the normal range                              
  • >3.0g – may indicate nephrotic syndrome

The post Urine Dipstick Urinalysis appeared first on almostadoctor.

Introduction

Almost every patient admitted to hospital will have their liver function tested, along with a full blood count, urea and electrolytes and glucose. Liver function tests (LFTs) are also one of the most commonly requested tests in primary care.

Interpreting liver function tests can be a tricky concept to understand. For starters, the term “liver function tests” is actually somewhat of a misnomer, and several authorities now recommend the term “liver blood tests” as an alternative. This is because only some of the tests included in a normal set of liver blood tests are actually tests of liver function. They are mainly indicators of liver damage or liver fibrosis. Tests that indicate the true synthetic function of the liver are not typically included in a standard set of “LFTs”.

A typical set of LFTs will include:

• Bilirubin – can show pre-hepatic, intra-hepatic and post-hepatic causes of jaundice. A patient won’t necessarily be visibly jaundiced if bilirubin is raised, especially if the bilirubin is not grossly elevated.
• ALP – can be raised by liver, bone and placental pathologies. When raised in liver disease it indicates biliary obstruction and hepatic metastasis
• ALT
• AST – is raised in liver and skeletal muscle pathologies
• Albumin – low albumin indicates capilliary leak
• GGT – is most useful to assess if raised ALP is due to liver, or other pathology.
• INR – is also usually measured in suspected liver disease. This is essentially a measure of the liver’s synthetic function, as it measures the liver’s ability to produce clotting factors. In hepatitis and other liver pathologies, a raised INR indicates significant liver damage

We can consider liver blood tests as being subdivided into three categories

• Indicators of liver damage e.g. in hepatitis, paracetamol overdose – hepatobiliary enzymes
  • ALT
  • AST
  • ALP
  • GGT – useful to discern if raised ALP is due to liver or bone (or rarely another) pathology
• Indicators of liver synthetic function (the true liver function tests) – indicators of severe advanced liver disease – e.g. alcohol liver disease
  • Bilirubin
  • Albumin
  • INR and other clotting function – particularly PT – prothrombin time
  • Platelets – synthesis of platelets requires production of thrombopoetin from the liver
• Indicators of liver fibrosis
  • Platelets – often considered along with albumin and INR as an indicator of liver function

When LFT’s are routinely measured (e.g. in primary care as a screening tool), an abnormality is found in 3.5% of people. 0.3% of patients have ALT levels 2x that of normal. Abnormal LFTs are unlikely to resolve spontaneously – and as such there is little benefit to simply repeating tests that are raised, without other investigation or management.
The majority of patients with abnormal test results have significant liver disease.
The two most common liver diseases are alcoholic liver disease, and non alcoholic fatty liver disease (NAFLD).
Normal LFT’s do not necessarily exclude the possibility of chronic liver disease.

In the case of raised liver blood tests, a liver screen is often performed to help identify the cause. Usually this includes:

• Autoantibodies and immunoglobulin – to look for autoimmune hepatitis
• Viral hepatitis serology (usually hepatitis B and hepatitis C)
• Ferritin – to look for haemochromatosis
• USS of the liver

ALT

• Can be raised up to 50x normal. When they are this high it suggests viral or drug induced hepatitis, or extensive hepatitis with necrosis of another source.
• Normal levels in infants are 2x that of adults
• This is an enzyme that catalyses a reaction between an amino acid and a keto-acid. Ultimately, they are important in producing various amino acids.
• Found mainly in the liver, but also smaller amounts in the kidneys, cardiac and skeletal muscle. It, however, is fairly specific for liver damage.
• During liver damage, ALT is released into serum causing raised levels that may remain high for weeks or months. Levels will be raised before jaundice appears.
• Levels of ALT fluctuate slightly throughout the day, and are particularly raised after exercise.
• It is generally raised in liver problems, and less so in problems with the bile duct. It may also be raised in heart problems.
• More specific for liver damage than AST.
• Levels of ALT and AST both raised above 2x normal then this is significant.
• If the transferases are very high (greater than 1000 U/L then the diagnosis is almost certainly hepatitis
• Alcoholic liver disease is unlikely cause an AST of >1000 u/L

AST

• Levels can go as high as 20x normal. This would normally indicate something like viral hepatitis, sever skeletal muscle trauma, extensive surgery, drug induced hepatic trauma,
• Levels from 10-20x normal may suggest MI, and alcoholic cirrhosis.
• 5-10x normal may suggest chronic cirrhosis
• Mildly raised levels are often found it fatty liver (steatosis), liver metastasis and PE.
• These type of enzymes have a similar function to ALT enzymes. These enzymes are found in the liver, RBC’s, cardiac and skeletal muscle, kidney and brain tissue. As a result, damage to any of these areas can result in an increased level on test result.
• It used to be used as a marker for MI, but is not specific enough, and has been superseded by tests for troponins.
• Remember, high levels are likely to be liver OR heart problems OR muscle damage (use other tests, namely ALT to help you decide)
• Levels of AST tend to fluctuate depending on the amount of current acute damage. So levels will be highly raised with a lot of current necrosis, and may only be very slightly raised if there is no current necrosis (even though there may be very severe disease present). Therefore, AST can be used as a monitoring mechanism.

ALP

• These enzymes work best in an alkaline environment are involved in hydrolysis reactions – i.e. they remove a phosphate group from a molecule.
• It is found in large concentrations in cells lining the bile duct and in bone. So when levels are raised in the plasma, it normally means damage to one of these areas. Levels can be physiologically elevated in times of high bone turnover, such as adolescence and in the third trimester of pregnancy.
• ALP is likely to be largely elevated in bile duct blockage, and slightly raised in liver disease (e.g. hepatitis or liver cancer)

Gamma-GT 

• Commonly raised in increased alcohol intake
• Also, very commonly a “false positive”
• Raised levels are common in obstruction of the bile ducts.
• GGT is often used to confirm that ALP readings are due to liver damage and not another cause.
  • If ↑ALP but normal GGT – likely bone – consider checking calcium
  • If ↑ALP and ↑GGT – likely liver cause
• GGT is used to particualrly monitor cirrhosis caused by alcoholism.
• In patients with known liver disease GGT is a strong predictor of mortality

Bilirubin

1-20 µmol/l
Most commonly used to asses for obstructive jaundice. Levels also likely to be raised in liver damage and in cases of severe RBC damage. Test for urobilinogen can be useful in determining whether it is due to RBC’s or a problem with the liver / bile system.

Albumin

33-49g/l
This is the major protein constituent of plasma, and accounts for over 50% of all plasma proteins. It is manufactured in the liver from ingested amno-acids. It helps to regulate osmotic pressure as well as transport nutrients and waste products.
It may often be reduced as a result of;

• Diarrhoea
• Liver disease
• Poor diet
• Iron deficiency
• Infection

Patterns of L​FT results

There are four main patterns of liver function test results, and these help identify what the cause of the abnormal results are. In reality, often there is a mixed picture, making interpretation much more difficult!

1. Obstructive aka Cholestatic Pattern – due to bile duct obstruction. Remember this could be any part of the ducts, even the tiny ones, within the liver itself, it doesn’t necessarily mean the common bile duct. This pattern will give:
   1. High bilirubin
   2. High ALP
   3. Normal ALT (or only slightly raised in comparison to ALP)
2. Hepatitic Pattern – this is a sign of acute liver inflammation. The pattern will give:
   1. Very high ALT – between 200- 2000 U/L
   2. Varying bilirubin – the higher the level, the greater the degree of damage
   3. Slightly raised ALP – should be no higher than 2x normal.
   4. Increased prothrombin time – usually will be slightly raised. In cases of severe liver failure it may exceed 25 seconds
3. Synthetic failure – an emergency presentation requiring urgent referral for ultrasound +/- urgent admission to hospital
   1. Jaundice (high bilirubin)
   2. Increased INR
   3. Low platelets
   4. Low Albumin
4. Isolated raised Bilirubin
   1. Usually the result of Gilbert’s Syndrome
   2. Check unconjugated and conjugated bilirubin to exclude hamolysis

Note that previous recommendations made a distinction between ALT or AST results <x2 normal and >x2 normal. The latest guidelines from the Royal Society of Gastroenterology no longer makes this distinction – as evidence suggests that the degree of elevation, and the duration of elevation does not correlate to the degree of liver disease. Therefore, any rise in these tests should be considered for further investigation. Liver disease is often “silent” until advanced.

Summary

Adapted from a table in – Davidson’s Principles and Practice of Medicine. 20^th ed. Churchill Livingstone, (2006), Boon, NA., Colledge, NR., Walker, BR. and updated with reference to Guidelines on the Management of abnormal liver blood tests by the Royal College of Gastroenterology, 2016. 

References

• Murtagh’s General Practice. 6th Ed. (2015) John Murtagh, Jill Rosenblatt
• Oxford Handbook of General Practice. 3rd Ed. (2010) Simon, C., Everitt, H., van Drop, F.
• Guidelines on the management of abnormal liver blood tests

Read more about our sources

The post LFTs – Liver Function Tests appeared first on almostadoctor.