CPT2: Lab Results

Question 1

What does measuring urea and electrolytes provide information on?

Answer 1

Gives information on:

• Kidney function
• Hydration Status
• Electrolyte status

Question 2

Why is it important to monitor renal function? Give examples

Answer 2

• Medicines may be highly dependant on the kidneys for excretion (morphine)
• Medicines might be nephrotoxic (Gentamycin)
• Medicines might effect water and electrolyte levels (Furosemide)
• Medicines may be toxic in states of electrolyte deficiency (Digoxin)
• Diseases can affect water and electrolyte balance (Diarrhoea, dehydration)

Question 3

Where is Na+ predominantly found?

What role does it play in the body?

Why is it importnat?

Answer 3

• Sodium is primarily an extracellular ion - it exists primarily outside of cells in the extracellular fluid.
• In certain tissues it moves into the cell for nerve conduction and muscle contraction.
• The concentration of sodium in the extracellular fluid (the osmolarity) is important for the control of water balance via the actions of ADH and aldosterone.

Question 4

What are causes of hyponaturameia?

Answer 4

• Fluid overload
  
  • (the amount of sodium in the body is unchanged but the amount of water in the body is increased - effectively diluting the patient). This can occur in patients who have large volumes of oedema like heart failure.
• Low sodium intake
  
  • ​ (‘Tea and toast’ diet, beer diet - both contain a poor amount of electrolytes)
• Increased sodium loss
  
  • ​(vomiting/diarrhoea, diuretics, mineralocorticoid deficiency)
• Syndrome of inappropriate ADH secretion (SIADH)
  
  • ​ antidepressants, carbamazepine, proton pump inhibitors. Increased ADH leads to water retention, increasing extracellular fluid, further diluting sodium level. As blood volume is increased, renin synthesis is suppressed, therefore less aldosterone is available to promote sodium reabsorption.

Question 5

Causes of hypernaturaemia?

Answer 5

Causes of hypernatremia:

• Dehydration
  
  • ​ (the amount of sodium in the body stays the same, but the amount of water in the body is reduced). Loss of large amounts of water via the urine (lithium, diabetes insipidus. Infection/ illness)
• Decreased excretion
  
  • (e.g. Cushing’s disease and other endocrine issues effecting the mineralocorticoid hormones, including use of corticosteroids)
• Increased intake of sodium
  
  • ​ (medications with a high concentration of sodium - antacids, soluble tablets, some IV preparations, over zealous use of sodium chloride given IV)

Question 6

What can hyper/hypo naturaeimia cause?

Answer 6

Both hyper and hyponatremia can cause muscular weakness and confusion.

Question 7

What is the balance between K+ and Na+ between cells maintained by?

Answer 7

Na+K+/ATPase

Question 8

Where is K+ predominantly found?

What does it play an important role in?

Answer 8

Potassium is primarily an intracellular ion - it exists primarily inside the cell in the intracellular fluid.

As with sodium, it is required for muscle contraction and nerve conduction.

Question 9

What can hypo/hyper kalaemia cause?

Answer 9

Both hyper and hypokalaemia can cause cardiac arrhythmias and muscle weakness.

Question 10

What are causes of hypokalaemia?

Answer 10

Causes of hypokalaemia:

• Increased potassium loss from the GI tract (vomiting, diarrhoea, laxative abuse)
• Increased movement of potassium into cells (salbutamol, insulin)
• Loss from the kidneys (thiazide and loop diuretics, corticosteroids)

Question 11

What are causes of hyperkalaemia?

Answer 11

• Reduced renal excretion (ACE inhibitors, potassium sparing diuretics like spironolactone, lithium, heparin)
• Increased intake of potassium (overuse of potassium supplements like Sando K)
• Severe tissue injury or hypoxia (Na+/K+/ATPase does not receive enough ATP to maintain the balance of Na+ and K+, leading K+ to leak out of the cell)

Question 12

Where does urea in the body come from?

What does urea help with?

Answer 12

When amino acids are broken down, they release ammonia which is toxic to the body. In order to detoxify and eliminate ammonia, it is converted to urea which can then be eliminated in urine.

It is filtered in the kidney, but undergoes a degree of reabsorption from the renal tubules to help with the reabsorption of water.

Question 13

What are causes of ureamea/ high urea levels?

Answer 13

Causes of high serum urea:

• Dehydration (the kidney reabsorbs more urea to help reabsorb more water)
• Kidney disease (less urea filtered due to damage to nephrons)
• High protein intake (more protein - more amino acids - more ammonia - more urea)

Question 14

What are causes of low urea levels?

Answer 14

Causes of low serum urea:

• Low protein diet (less protein - less amino acids - less ammonia - less urea)
• Severe liver disease (less production of urea from ammonia)

Question 15

What can high levels of urea lead cause?

What about low levels?

Answer 15

The build up of urea in the body can lead to nausea and vomiting as well as changes in mental state, but this usually only occurs when the urea is very high and in persons with chronic kidney disease.

Not usually a cause for concern, but it may indicate the above conditions. Better to take other clinical factors into account when concerned about the above conditions - signs/symptoms of liver disease or malnutrition.

Question 16

Where does creatinine come from?

What is the pharmacokinetics?

Useful for?

Answer 16

Creatinine is a breakdown product from muscle and undergoes a negligible amount of reabsorption in the kidney and so the majority is eliminated in urine. It is therefore a useful indicator of renal function.

Question 17

What are creatinine levels affected by?

Answer 17

Be aware that the amount of creatinine is affected by the muscle mass of the individual (more muscle, more creatinine) and the age of the individual (higher age, generally a lower muscle mass therefore less creatinine).

Question 18

What are causes of low creatinine concentrations?

Answer 18

Low muscle mass

Question 19

What are causes of high creatinine concentrations

Answer 19

Causes of high serum creatinine:

• Kidney dysfunction - less creatinine is filtered and excreted in urine. Therefore more creatinine is found in the blood.
• High muscle mass (e.g. bodybuilders/athletes) - This does not mean however that the kidneys are dysfunctional.
• Some medicines like trimethoprim interfere with creatinine secretion, causing a rise in serum creatinine. This does not affect the kidney function however.

Question 20

What are normal and abnormal eGFRs?

Answer 20

Above 60 - 90 ml/min/1.73m2 is considered to be normal renal function and will simply be quoted as >60ml/min/1.73m2.

Values less than 60ml/min/1.73m2 are considered to be abnormal and will be quoted as a specific number e.g. 35ml/min/1.73m2.

Question 21

What does FBC give information on?

Answer 21

The full blood count is another very common test that provides information about:

• The quality and quantity of cells found in the bloodstream.
• Bone marrow function
• Immune system function

Question 22

Why is it important to monitor FBC? Give examples

Answer 22

• These are important parameters to be aware of when diagnosing, treating and monitoring patients because:
• Medicines may have a toxic effect on bone marrow (e.g. methotrexate)
• We need to monitor the patient’s response to treatment (e.g. pneumonia treated with amoxicillin)
• Disease can affect the quality or quantity of cells found in the blood (e.g. red blood cells and anaemia)
• Medicines may cause harm if a patient is deficient in a particular cell (e.g. warfarin and low platelets)

Question 23

What is Hb?

Answer 23

Haemoglobin is a protein which is carried by red blood cells. It is able to bind oxygen and transport this to the tissues for its role in energy production.

Question 24

symptoms of low Hb?

Answer 24

Symptoms of low Hb can include fatigue, changes to the nails and hair and tiredness. Very low Hb can cause breathlessness as well as chest pain, due to poor oxygen supply to tissues.

Question 25

Where are RBC produced and by which process?

What is their function?

Answer 25

Red blood cells (RBC) or erythrocytes are produced in the bone marrow as part of the process of erythropoiesis.

They contain haemoglobin which transports oxygen from the lungs to the cells.

Question 26

Causes of low RBC?

Answer 26

As RBCs are produced by the bone marrow, low RBC count may indicate an issue with bone marrow caused by medicines that suppress the function of cells in bone marrow like methotrexate, carbimazole or chemotherapy.

Low RBCs may also be caused by destruction of RBCs in the blood - this is may be due to a genetic disorder like G6PD deficiency, infection, an immune process or exposure to chemicals or certain medicines like methyldopa (uncommonly used for hypertension).

Question 27

What is MCV

What can this measurment be used for?

What are classes of MCV?

Answer 27

The mean cell volume (MCV) is the average volume of the red cell, it is used to differentiate between types of anaemia - this will be covered in greater detail in the anaemia sessions.

Normal cells are referred to as normocytic, small cells are microcytic and large cells are macrocytic.

Question 28

What is Mean cell haemoglobin (MCH)?

What are classes of MCH?

Use of this measurement?

Answer 28

Mean cell haemoglobin (MCH) is the average mass of haemoglobin in one red cell. This again can be used to differentiate between types of anaemia.

Normal cells are referred to as normochromic, but cells will less haemoglobin will be paler in colour than normal cells and are therefore referred to as hypochromic. Cells with a greater amount of Hb are referred to as hyperchromic.

Question 29

Where are platlets produced?

Function of platlets?

Answer 29

Platelets are produced in the bone marrow for the purpose of maintaining haemostasis - i.e. forming clots and promoting tissue healing in response to injury.

Question 30

What can cause low platlet numbers?

What is this called?

Answer 30

As platelets are produced in bone marrow, their production can supressed by medications like methotrexate, carbimazole or chemotherapy that can supress the bone marrow. This results in a decrease in the number of circulating platelets called thrombocytopenia.

Question 31

What needs to be done in patients with thrombocytopenia?

Answer 31

Patients with low platelets are at risk of bleeding and so require a review of any medications which may increase risks of bleeding e.g. aspirin or warfarin.

Question 32

What can cause an increase in platlet number and what is this called?

Answer 32

The number of platelets may also increase due to the effects of inflammation, this is called thrombocytosis.

Question 33

What is WCC?

Where are the produced?

What does the test comprise of?

Answer 33

The white cell count (WCC) is the total count of the white cells in the blood.

This test is comprised of:

• Neutrophils
• Basophils.
• Eosinophils.
• Monocytes.
• Lymphocytes.

Question 34

When do raised levels of the following occur:

1. Neutrophils
2. Basophils.
3. Eosinophils.
4. Monocytes.
5. Lymphocytes.

Answer 34

1. Neutrophils (normally the largest white cell group). Neutrophils will be raised in infection, particularly bacterial infection, and inflammation.
2. Basophils. Can be raised in allergy or chronic inflammation - rarely raised in isolation.
3. Eosinophils. Often raised in parasitic infection or allergic conditions like asthma.
4. Monocytes. Often raised in specific infection like tuberculosis.
5. Lymphocytes. Often raised in viral infections. These will differentiate into T or B lymphocytes.

Question 35

What can cause low levels of WCC (especialy neutrophils)

Answer 35

All of the white cells are originally derived from the bone marrow and so any insult to the health of bone marrow through drugs or disease will effect the production of these cells. One particular case is neutropenia (low neutrophil count) caused by chemotherapy, as some chemotherapy agents have a toxic effect on bone marrow. This effectively leaves the patient with a deficiency in neutrophils which are required to fight infection - this is a risk for developing infection.

Question 36

What do LFTs give us information on?

Answer 36

• Liver cell function and integrity
• Gallbladder and biliary tree function
• Nutritional status

Question 37

Why is it important to monitor liver function?

Answer 37

• These are important parameters to be aware of when diagnosing, treating and monitoring patients because:
• Prodrugs depend on the liver for activation (e.g. codeine)
• Medicines may be toxic to the liver (e.g. statins)
• Some medicines depend on the liver for metabolism (phase 1 and 2) and detoxification (e.g. diazepam)
• Disease can affect the function of the liver/biliary system (e.g. alcoholic liver disease)
• Some medicines require substances produced in the liver for their efficacy (e.g. albumin and phenytoin)

Question 38

Describe the pathway of bile through the liver

Answer 38

Question 39

What are Alanine and asparte amino transferase and what is there role

Answer 39

Alanine and aspartate aminotransferase are important enzymes in the production of pyruvic acid during gluconeogenesis - they assist in catalysing steps that convert amino acids into pyruvic acid which can be converted into glucose or used in Kreb’s cycle.

Question 40

Where is ALT found?

What is ALT useful in determining?

Answer 40

ALT is made and found primarily in the liver (but to some extent in skeletal muscle too) and so is very useful in determining the function of the liver. It is stored in the cytoplasm of hepatocytes and the serum level gives an indication of hepatocyte integrity. When the serum level of ALT is high, it suggests that ALT is leaking out of the hepatocyte and into the bloodstream, suggesting that the plasma membrane of the hepatocyte is damaged.

Question 41

Where is AST found?

What does it tell us?

Answer 41

AST is found in several tissues including the liver, skeletal muscle, brain and cardiac muscle. This makes it less specific for monitoring the function of the liver and as such is not routinely included in a liver function test.

Question 42

What are potential causes of raised ALT?

Answer 42

Causes of raised ALT:

• Hepatotoxicity from medication. This can be a direct toxic effect on the hepatocytes. (statins, antifungals, rifampicin, paracetamol overdose, methotrexate).
• Disease of the liver (hepatitis C, alcoholism, liver ischemia, cancer)
• Hepatotoxicity from other substances (industrial chemicals, mushrooms)
• Cholestasis - bile acid build up can lead to hepatocyte damage - in this case ALP and GGT will also be raised.

Question 43

ALT low levels?

Answer 43

Not a concern

Question 44

What is alkaline phosphate?

What does it do?

Answer 44

Alkaline phosphatase (ALP) is an enzyme that is found in a wide variety of tissues where it assists in transport of metabolites as well as in bone formation. As it is a phosphatase, it is able to remove large phosphate groups from molecules, increasing their ability to be transported.

Question 45

Where is ALP found?

What is it useful for?

What must you be careful when interpretating this?

Answer 45

The majority of ALP in the body is found in bone, the placenta (if pregnant) and on the epithelial cells of the tubes that collect bile produced by hepatocytes, this makes ALP useful in detecting damage or obstruction to the bile ducts. When bile acid accumulates, more ALP is produced in response, this can leak into the circulation and be detected in an LFT.

Since it is also found in bone, we must be careful when interpreting raised ALP as it may have come from bone.

Question 46

Causes of raised ALP?

Answer 46

Causes of raised ALP:

• Obstructive cholestasis - Obstruction of the bile ducts due to a gallstone, tumour or narrowing of the bile ducts.
• Hepatocellular cholestasis - reduction in bile acid secretion from hepatocytes due to medicines (flucloxacillin, co-amoxiclav, azathioprine, oestrogen containing contraceptives, steroids), pregnancy or genetic predisposition.
• Bone disorders (healing fractures, bone cancers/bone metastasis)

The mechanisms and causes of cholestasis are complicated, but the most important thing to take away is that there are two basic mechanisms for raised ALP. You may encounter patients treated with a medication that can cause cholestasis (e.g. flucloxacillin) so it is important to know that when monitoring for this particular side effect of flucloxacillin, you must look at the LFT and the ALP/GGT in particular.

Question 47

Low levels of ALP?

Answer 47

Not a concern

Question 48

What is Gamma-glutamyltransferase (GGT)?

Where is it found?

Answer 48

GGT is an enzyme that is found in the liver and is also produced in the epithelial cells that line the bile collecting tubes in the liver.

Question 49

What is GGT used for?

Answer 49

It is not very specific for a particular type of liver disorder (i.e. hepatocyte damage or cholestasis) as it can be raised in both instances. It can also be induced by alcohol or medications, even in the absence of a liver disorder.

However, it is very useful when determining if a rise in ALP is due to bone or liver dysfunction. If ALP is raised along with GGT, it suggests that the cause of the ALP rise is due to a cholestatic problem. If ALP is raised without a rise in GGT, it suggests a problem with bone.

Question 50

Causes of raised GGT?

Answer 50

• Cholestasis (reduction in flow of bile acids from the liver through the bile ducts to the small intestine)
• Hepatocyte damage
• Enzyme induction (alcohol, rifampicin, phenytoin)

Question 51

Low levels GGT?

Answer 51

Not a concern

Question 52

What is bilrubin?

How is it excreted?

Answer 52

Bilirubin is a breakdown product of red blood cells, the haem group in haemoglobin specifically.

This initial form of bilirubin is known as unconjugated bilirubin and is insoluble in water, making it difficult to excrete as waste. It is therefore transported to the liver by albumin where it is conjugated with glucuronic acid to make it more water soluble. It is then secreted from hepatocytes into bile which enters the small intestine and eventually eliminated in faeces. A small proportion is excreted in the urine after enterohepatic recycling.

Question 53

What is high levels of billrubin called?

What are signs?

Answer 53

When bilirubin is raised significantly it leads to yellowing of the skin and the sclera (whites) of the the eyes, known as jaundice. This is because bilirubin has a yellow colour.

An elevated level of bilirubin is called hyperbilirubinemia.

Question 54

Causes of hyperbillrubinemia

Answer 54

Causes of elevated bilirubin:

Increased destruction of red blood cells

Accumulation of bile (cholestasis - hepatocellular or obstructive)

Hepatocyte damage (bilirubin can leak from hepatocytes into the bloodstream)

Impaired hepatic bilirubin conjugation (genetics)

Lab results usually provide a ‘total bilirubin’ - measuring both the unconjugated and conjugated bilirubin concentration. When necessary the unconjugated fraction and the conjugated fraction can be measured separately.

Question 55

Low billrubin levels?

Answer 55

Not a concern

Question 56

What is albumin and where is it synthesised?

What is its role?

Answer 56

Albumin is a protein that is synthesized in the liver and plays an important role in maintaining the oncotic pressure that keeps fluid within the vasculature and binding and transporting a number of molecules around the body (bilirubin, calcium, some drugs like phenytoin or digoxin).

Question 57

What do low levels mean and what can it lead too?

Answer 57

If albumin is low, it suggests the synthetic capability of the liver is reduced and can lead to fluid leaking from the vasculature causing oedema. We must also consider highly protein bound drugs like phenytoin - the ‘free’ unbound fraction of the drug will increase if the patient has low albumin perhaps leading to toxicity.

Question 58

Causes of low levels of albumin?

Answer 58

Causes of low albumin:

• Liver disease (hepatocyte damage, reduced ability to synthesise)
• Malnutrition (less amino acids available to produce albumin)
• Loss from the kidneys (nephrotic syndrome, glomerular damage)

Question 59

High levels of albumin?

Answer 59

Not a concern

Question 60

What is CRP and what does it mean when it is raised?

Answer 60

C reactive protein (CRP) is an acute phase protein - it is raised in response to tissue damage and inflammation, where it stimulates the immune system and activates the complement cascade. As many different causes of inflammation can stimulate the production of CRP, it is said to be non-specific i.e. it cannot differentiate between inflammation caused by infection or inflammation caused by rheumatoid arthritis.

Question 61

What are CRP levels determined by?

What can this be used for?

Answer 61

The level of CRP is determined by its rate of synthesis which reflects the intensity of the inflammatory process - more inflammation, more CRP. It can be useful to monitor the treatment progress for a patient using CRP amongst other values, for example: monitoring antibiotic treatment for pneumonia - as the patient recovers, we should expect to see a gradual reduction in neutrophils, WCC and CRP.

Question 62

What does blood glucose give a measurement off?

Answer 62

Blood glucose (BM) is simply an instantaneous measurement of the circulating glucose. It is useful for the monitoring patients with diabetes mellitus who may need to adjust their dose of insulin based on their blood glucose. It cannot give an indication of long term glucose control as it only indicates the glucose at the point in time when the sample is taken. An isolated sample may show high BMs but this may be due to the patient having a meal recently and in actual fact their BMs are normal between meals.

Question 63

What is blood glucose measurement useful for?

Answer 63

The natural variability of BM throughout the day makes it less useful for diagnosis, but it is useful for short term monitoring for a patient who is on medications that may effect blood glucose - steroids, sulphonylureas, insulin.

Question 64

What should levels for blood glucose be:

1. Before and after a meal (no diabetes)
   
   1. Before and after a meal (diabetes)

Answer 64

Non diabetic patients should have a fasting BM between 4.0 - 5.9 mmol/L and a post meal BM of up to 7.8mmol/L.

Diabetic patients, especially those who are poorly controlled, may have BMs beyond 20 mmol/L. This is due to the absence of insulin (type 1) or the reduced sensitivity to insulin (type 2).

Diabetic patients should maintain their BM between 4-7mmol/L before meals and less than 9.0 mmol/L after meals, although these targets may be relaxed in certain situations to avoid the risk of hypoglycaemia.

Question 65

How is blood glucose taken

Answer 65

BM is not usually a laboratory test - it is more commonly done at the patient’s bedside by doing a fingerprick test, known as capillary blood glucose. It is easier and faster to do it in this way - some patients may receive BMs before each meal and perhaps more in a day, this would amount to a lot of work for a laboratory and a lot of waiting for the results for the ward staff.

Question 66

What is HbA1c?

What does it show?

Answer 66

Glycated haemoglobin (HbA1c) is a measurement of the proportion of haemoglobin that becomes bound with glucose in the circulation. The amount of glucose in the bloodstream is proportional to the amount of HbA1c produced therefore HbA1c can provide an indirect measurement of glucose control. As red blood cells remain in the blood for up to 120 days, the HbA1c can give an impression of glucose control over 2-3 months. This makes it useful in the long term monitoring of diabetic control or diagnosis of diabetes mellitus.

Question 67

Tareget ranges of Hb1Ac for diabetic and non-diabetic patients

Answer 67

Non diabetic patients should have an HbA1c of <42mmol/mol, whereas patients with diabetes will have an HbA1c of 48mmol/mol or greater.

Diabetic patients will usually have an HbA1c target of 48mmol/mol or less. Some may have a more relaxed target due to concerns about hypoglycaemia caused by antidiabetic treatment.

Question 68

What do high differing levels of folate, Vit B12 and ferritain mean?

Answer 68

Vitamin B12 and folic acid (vitamin B9) are consumed as part of the diet and are required for many cellular functions - including the synthesis of red blood cells. A deficiency of either or both can lead to a type of anaemia characterised by a raised MCV, known as macrocytic anaemia.

Ferritin is the major protein that stores excess iron in the body. It is able to release iron when required for the production of haemoglobin. Low ferritin suggests a deficiency in iron (commonly in iron deficiency anaemia), whereas high ferritin can be a sign of inflammation as ferritin, like CRP, is an acute phase protein - this can complicate the assessment of ferritin in a patient with an inflammatory disease (like ulcerative colitis).