High liver enzymes numbers: Normal, High, and Low Ranges, Chart & Results
Elevated Liver Enzymes: Causes & Symptoms
Liver and other organs in the abdomen
What does the liver do and what are elevated liver enzymes?
The liver is the body’s largest internal organ. It is located below the diaphragm on the right side of the abdomen. The liver performs many functions, including the following:
- Produces most of the proteins the body needs.
- Metabolizes (breaks down) nutrients from food to produce energy.
- Prevents shortages of nutrients by storing certain vitamins, minerals, and sugar.
- Produces bile, a substance that helps digest fat and absorb vitamins A, D, E and K.
- Produces substances that help with blood clotting.
- Helps your body fight infection by removing bacteria from the blood.
- Removes potentially poisonous byproducts of certain medications.
What are liver enzymes?
An enzyme is a chemical that accelerates (speeds up) chemical reactions within the body. There are several enzymes in the liver, including alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transpeptidase (GGT). Elevated liver enzymes, found with a blood test, indicate inflamed or injured liver cells.
Why does a doctor check for elevated liver enzymes?
A doctor may order a liver enzyme test if a patient is being treated for liver disease or has a higher risk for liver disease. For instance, if the liver is injured, ALT is released into the bloodstream, and levels of this enzyme would be elevated.
What causes elevated liver enzymes?
Certain diseases or situations can cause a rise in liver enzymes, including:
- Hepatitis (inflammation, or swelling, of the liver).
- Fatty liver disease (a buildup of certain fats in the liver).
- Metabolic syndrome (a collection of heart disease risk factors that increase the chance of developing heart disease, stroke, and diabetes).
- Cirrhosis (the liver tissue is filled with scar tissue).
- Drug abuse.
What are the signs and symptoms of elevated liver enzymes?
Elevated liver enzymes usually have no signs or symptoms on their own. The doctor may check for elevated liver enzymes in patients who might have hepatitis. The symptoms of hepatitis include:
- Jaundice (a yellowing of the skin, whites of the eyes, and mucous membranes caused by liver problems).
- Pain or swelling in the abdomen.
- Nausea and vomiting.
- Dark urine.
- Pale-colored stools.
- Poor appetite.
The doctor may also order a liver enzyme test for patients who:
- Drink a great deal of alcohol or abuse drugs.
- Have a family history of liver disease.
- Are overweight.
- Have diabetes.
Care and Treatment
What is the treatment for someone who has elevated liver enzymes?
Depending on what is causing the rise in liver enzymes, your doctor may advise you to stop drinking alcohol or using certain drugs, lose weight, or eat a healthier diet. If your liver enzymes remain elevated, your doctor may order other tests, or may refer you to a specialist in liver diseases.
Elevated liver enzymes – Drugs.com
- Mayo Clinic Symptom Guide
- Elevated liver enzymes
Medically reviewed by Drugs.com. Last updated on March 5, 2020.
Elevated liver enzymes often indicate inflammation or damage to cells in the liver. Inflamed or injured liver cells leak higher than normal amounts of certain chemicals, including liver enzymes, into the bloodstream, elevating liver enzymes on blood tests.
The elevated liver enzymes most commonly found are:
- Alanine transaminase (ALT)
- Aspartate transaminase (AST)
- Alkaline phosphatase (ALP)
- Gamma-glutamyl transpeptidase (GGT)
Elevated liver enzymes might be discovered during routine blood testing. In most cases, liver enzyme levels are only mildly and temporarily elevated. Most of the time, elevated liver enzymes don’t signal a chronic, serious liver problem.
Many diseases and conditions can contribute to elevated liver enzymes. Your doctor determines the cause by reviewing your medications, your signs and symptoms and, in some cases, other tests and procedures.
More common causes of elevated liver enzymes include:
- Over-the-counter pain medications, particularly acetaminophen (Tylenol, others)
- Certain prescription medications, including statin drugs used to control cholesterol
- Drinking alcohol
- Heart failure
- Hepatitis A
- Hepatitis B
- Hepatitis C
- Nonalcoholic fatty liver disease
Other possible causes of elevated liver enzymes include:
- Alcoholic hepatitis (severe liver inflammation caused by excessive alcohol consumption)
- Autoimmune hepatitis (liver inflammation caused by an autoimmune disorder)
- Celiac disease (small intestine damage caused by gluten)
- Cytomegalovirus (CMV) infection
- Epstein-Barr virus
- Hemochromatosis (too much iron stored in your body)
- Liver cancer
- Polymyositis (inflammatory disease that causes muscle weakness)
- Sepsis (an overwhelming bloodstream infection that uses up neutrophils faster than they can be produced)
- Thyroid disorders
- Toxic hepatitis (liver inflammation caused by drugs or toxins)
- Wilson’s disease (too much copper stored in your body)
When to see a doctor
If a blood test reveals you have elevated liver enzymes, ask your doctor what the results might mean. Your doctor might suggest you undergo other tests and procedures to determine what’s causing your elevated liver enzymes.
© 1998-2019 Mayo Foundation for Medical Education and Research (MFMER). All rights reserved.
Abnormal Liver Function Tests | Patient
What are liver function tests?
Liver function tests measure a series of chemicals which relate to the way the liver works. They include substances that are made in the liver or affected by the health of the liver cells, chemicals which are processed or excreted by the liver, and hormones that the liver makes in order to do its work.
Liver function tests are aimed at giving a picture of the ‘state’ of your liver. They are a sensitive way of looking for liver strain or liver damage, as they often show this well before you get any symptoms or problems with your liver. This means that the cause of liver strain or damage can be diagnosed and, often, reversed.
Liver function tests are also used for monitoring in cases of known liver inflammation, injury or disease.
Where and what is the liver, and what does it do?
The liver is your largest internal organ. It sits in the tummy (abdomen), under your diaphragm on the right-hand side. It is usually tucked under the ribs, which protect it, although in some people the edge of the liver protrudes slightly. If the liver is swollen, through inflammation or disease, it can swell out from under the ribs and make your tummy swollen.
Diagram showing the liver
The liver is a factory for the production and breakdown of carbohydrates, fats, proteins, hormones and other essential body chemicals, and helps dispose of waste products. This work is mainly carried out by liver cells (hepatocytes). Some of the most important functions include:
Production of these substances
- Glycogen (a carbohydrate energy store), which it makes from glucose.
- Glucose, made and released into the blood from glycogen, proteins and fats.
- Many essential proteins and amino acids (building blocks of proteins).
- Many of the clotting factors that help your blood to clot normally.
- Plays a part in red blood cell production.
- Albumin, the main protein in your blood, which bulks out your serum and enables it to carry essential substances around the body.
- Angiotensinogen, which plays a role in blood pressure control.
- Thrombopoietin, which regulates some of the work of your bone marrow.
- Cholesterol, triglycerides, lipoproteins and fats – as part of the management of fat stores in your body.
- Bile, excreted into the intestine for absorbing fats and vitamin K.
- Hormones that help children grow and that build muscle in adults.
Breakdown of these substances
- Excess hormones, including insulin.
- Bilirubin, which is a waste product from worn-out blood cells.
- Many waste products.
- A wide range of toxic substances and medicines, including alcohol.
- Foreign proteins that reach it from the digestive system (trapped and destroyed by specialised immune cells in the liver).
Storage of these (and other) substances
- Glucose (as glycogen).
- Vitamin A (1-2 years’ supply).
- Vitamin D (1-4 months’ supply).
- Vitamin B12 (3-5 years’ supply).
- Vitamin K.
- Iron and copper.
What liver function tests are there?
The usual liver function tests typically include the following:
- Total protein.
- Transferases (AST or SGOT and ALT or SGPT).
- Gamma GT.
- Creatine kinase.
- Calcium and corrected calcium.
- Prothrombin time or International Normalised Ratio (INR).
Each of these is discussed below. The liver performs hundreds of different functions, so there are many other possible tests that look at its health. These would normally be done if an abnormality is found with the basic liver function tests described here, or if a specific problem is suspected. They might include:
- Virus tests – for example, for hepatitis A, B or C – to look for the cause of disease.
- Autoantibody tests (to detect and monitor immune diseases).
- Immunoglobulins (antibodies made in response to various challenges including allergies, infections, some blood disorders and some cancers).
- Serum ferritin and transferrin saturation (measures of iron storage and management by your body).
- Alpha-fetoprotein (maternal levels help look at the health of the baby during pregnancy, and levels are also raised in some cancers).
- Copper/caeruloplasmin (measures of copper management by the body).
- Alpha-1 antitrypsin (a hormone involved in protecting liver and lung cells from injury).
- Clotting factors (particularly if there is a suspicion that your blood is not clotting well or you have severe liver disease).
What can cause your liver function tests to be abnormal?
Your liver tests can be abnormal because:
- Your liver is inflamed (for example, by infection, toxic substances like alcohol and some medicines, or by an immune condition).
- Your liver cells have been damaged (for example, by toxic substances, such as alcohol, paracetamol, poisons).
- Your liver is having to work harder to process medicines or toxic substances (for example, alcohol, paracetamol, poisons).
- The bile drainage from your liver is blocked – for example, by a gallstone.
- There is a swelling inside your liver (for example, an abscess or a tumour).
- You have an underlying condition that affects the liver’s production and storage abilities (for example, Wilson’s disease, haemochromatosis, Gilbert’s syndrome). In these cases the abnormality of your liver tests will be a feature of your condition, and may be normal for you.
- Your liver is physically injured (for example, trauma).
- You fall just outside the normal limits (see below).
What does the ‘normal range’ mean in liver function tests?
The ‘normal range’ is a range of values given by the local laboratory for liver function tests. The range varies slightly between laboratories according to the measurement methods that they use.
The ‘normal’ limits are defined by laboratories as the range of levels inside which 19 of every 20 people with healthy livers will fall. This means that, for any one liver test, around 1 in 20 people with healthy livers will have a result that is slightly abnormal. There will, in the majority of cases, be nothing wrong with their liver; having a test that’s just over the edge usually means nothing, as long as – crucially – there is only one slight abnormality out of the whole range of tests. You should always discuss even a slightly abnormal result with your doctor.
What should I do if my liver function tests are abnormal?
You are likely to find out that your liver tests are abnormal from your healthcare provider, who will tell you what you need to do next. However, if you obtain your test results without explanation, you should contact your healthcare provider to discuss them.
Doctors consider a slightly abnormal liver function test as one that is less than twice the upper limit of the ‘normal’ value. Doctors consider a very abnormal liver function test as one that is more than twice the upper limit of the ‘normal’ value.
- If the tests are very mildly abnormal, only one or two tests are affected and you are perfectly well then this would not normally need an urgent consultation. However, you should speak to a health professional for advice within a few days (in case more tests or monitoring need to be done).
- If you have multiple abnormalities on your tests, if some of the tests are very abnormal or if you are also unwell or in pain then you should seek medical advice more urgently.
- If you have known liver disease and your liver function tests have altered significantly since the last time they were checked, you should seek medical advice the same day unless you have a standing instruction to do something different.
- Sometimes an abnormal liver function test is normal for you. If you already know this is the case then it may be that no action is needed. A common example of this is Gilbert’s syndrome, when you have a naturally raised level of bilirubin but other liver function tests are normal and you are well. Your doctor will tell you if you have Gilbert’s syndrome.
What will my doctor do if I have abnormal liver function tests?
All abnormal liver function tests need explanation, even if that explanation is that you are one of the 5% who fall outside the ‘normal’ range. In many cases, a single, isolated, slightly abnormal liver function test in a well patient will not signify an underlying problem. However, some liver disorders, including early signs of overuse of alcohol, can produce slight changes (especially at first), so it’s important to be sure.
Your doctor will want to do further tests and to see, question and examine you, to determine the reason for the blood test abnormality. If you are otherwise well, this will initially be done in primary care. Options include:
- Repeating the blood test.
- Further blood tests in order to discover or rule out particular causes.
- An ultrasound scan of your liver and gallbladder.
- A liver biopsy, to work out exactly what is going on.
- Depending on the severity and suspected cause, referral to a liver specialist for advice, more specialist tests and liver biopsy.
- If you are very unwell, you may need referral or admission to hospital.
Can my doctor make a diagnosis from my liver function test?
Sometimes. Single abnormalities in the tests do not give diagnoses on their own but the pattern of abnormalities can point to the most likely cause of the problem. When this is combined with speaking to and examining you, your doctor may be able to make a clear diagnosis.
Once the cause of the abnormality has been determined, your doctor will discuss what you need to do next.
What do unusually low levels on my liver function tests mean?
Note that in most cases (except albumin and calcium) it is a raised (rather than a lowered) level in the liver function test which may indicate a problem. In the following descriptions, where low levels can be significant for your health they are also described.
What does an abnormal bilirubin level mean?
Bilirubin comes from the breakdown of red blood cells in the body. The liver processes (conjugates) bilirubin so that it can be excreted via the kidneys. A high bilirubin level can make you appear jaundiced (with a yellow tinge to the skin and to the whites of the eyes).
The most likely cause of raised bilirubin depends on whether the rise is in bilirubin that the liver has already processed (conjugated bilirubin), in the bilirubin that the liver has not yet processed (unconjugated bilirubin), or in both.
A rise in both types of bilirubin
Conjugated bilirubin tends to rise if the flow of bile in the tiny tubes within the liver is blocked, and unconjugated bilirubin tends to rise if the liver calls cannot do their work (or there is too much work for them to do). If the liver is both damaged (not working properly) and swollen or scarred (blocking the drainage system) then both types of bilirubin will tend to rise.
An isolated rise in unconjugated bilirubin
Unconjugated bilirubin may increase because the liver can’t process the bilirubin, or because the body is making an excess of bilirubin by breaking down too many blood cells, and the liver is normal but can’t keep up.
An isolated rise in conjugated bilirubin
Increased conjugated bilirubin suggests that the liver is conjugating the bilirubin properly (the job of liver cells) but not excreting it properly via the bile ducts. Causes include:
- Reactions to some medicines, including common ones such as blood pressure tablets, hormones (for example, oestrogen), antibiotics (particularly erythromycin and flucloxacillin), tricyclic antidepressants and anabolic steroids.
- Some autoimmune diseases that affect bile excretion.
- Blockage of the bile ducts – for example, by a gallstone.
- Dubin-Johnson syndrome and Rotor’s syndrome.
- In babies a rise in conjugated bilirubin can signify rare but serious problems with the development of the bile drainage system in the liver, such as biliary atresia.
What does an abnormal albumin level mean?
Albumin is the main protein in your serum, and its level is a good guide to long-term liver health. Albumin levels that are abnormally low have the greatest significance for the liver.
Low levels of albumin
This can be due to:
- Severe liver disease.
- Poor nutrition.
- Malabsorption of protein (for example, in Crohn’s disease or in coeliac disease).
- Protein-losing enteropathies (for example, severe bowel inflammation or infection such as cholera).
- Protein loss through kidney problems (for example, nephrotic syndrome).
- Failure of protein manufacture through severe liver inflammation.
- Albumin levels also fall if you lose protein through your skin (for example, in extensive skin inflammation and widespread burns).
- Albumin levels decrease during pregnancy, when your blood is more dilute.
High levels of albumin
This is usually due to having the tourniquet on for too long before your blood sample is taken. Sometimes it can be due to a very high-protein diet, as in bodybuilders, or to lack of fluid in the body (dehydration), when the blood is more concentrated.
What does an abnormal total protein level
Total protein measures the total of albumin and globulins. It is usually normal in liver disease even if albumin levels are low, as globulin levels tend to increase as albumin levels fall.
- High values of total protein are seen in chronic active hepatitis and alcoholic hepatitis.
- High values of total protein are also seen in conditions outside the liver which increase globulins (such as myeloma) and conditions involving overactivity of the immune system (such as severe infection and chronic inflammatory disease).
- Low levels of total protein can sometimes be seen in severe liver disease, in conditions of severe protein loss (such as widespread burns) and in severe malnutrition.
What does an abnormal ALT (SGPT), AST (SGOT) or creatine kinase level mean?
These substances are also called transferases. They are liver hormones (proteins which help do the work of the liver) which are normally found inside liver cells rather than in the blood.
- ALT stands for alanine transaminase and is also called SGPT (serum glutamic-pyruvic transaminase).
- AST stands for aspartate transaminase and is also called SGOT (serum glutamic oxaloacetic transaminase).
- Creatine kinase is sometimes checked along with AST and ALT.
If blood levels of transaminases go up this suggests leakage from damaged liver cells due to inflammation or cell death. AST and ALT tend to be high in liver disease and very high in liver inflammation.
- ALT is mainly found in the liver. AST is also found in muscle and red blood cells.
- ALT rises more than AST in acute liver damage.
- In chronic liver disease (for example, alcoholic cirrhosis) ALT is higher than AST; in cirrhosis AST is higher than ALT.
- Lower-than-normal levels of transaminases do not signify disease.
Creatine kinase comes mainly from muscle, so if it is raised alongside AST and ALT it suggests that the liver may not be the main source of the problem.
Causes of mild rises in transferases
Causes of marked increases in transferases
Marked increases are usually caused by acute injury to the liver by viruses, shortage of oxygen (ischaemia) or toxic substances. Causes include:
What does an abnormal gamma-glutamyl transferase level mean?
Gamma-glutamyltransferase (GGT) levels increase in most liver diseases. This test is very sensitive, although it also goes up in some heart, lung and kidney conditions.
- The most common reason for GGT increasing as a single abnormality is drinking more alcohol than your liver can easily cope with. GGT levels can be 10 times normal. The rise is a sign your liver is under strain and is at risk of being damaged by alcohol.
- GGT rises to 2-3 times the upper limit of normal in non-alcoholic fatty liver disease (NAFLD). This condition is increasingly common and can progress to scarring or inflammation of the liver. Transaminase levels also tend to rise in NAFLD.
- Some prescribed and over-the-counter medicines can increase GGT levels.
- GGT rises in some patients with chronic hepatitis C infection.
- In chronic liver disease, a rise in GGT suggests bile duct damage and scarring.
What does an abnormal alkaline phosphatase level mean?
Alkaline phosphatase (ALP) comes mainly from the cells lining bile ducts and from bones – particularly growing bones. It rises if there is slow or blocked flow in the bile ducts, if the bile ducts are damaged and in bone disorders. If the cause is in the liver, the GGT is also abnormal, whereas if it’s the bone, the GGT is usually normal. ALP is also raised during the third trimester of pregnancy.
Common causes of raised ALP with other abnormalities on your tests include:
Isolated raised ALP can occur in:
What do abnormal calcium and corrected calcium levels mean?
99% of the body’s calcium is stored in the bones, with the remaining 1% stored in other tissues, including the blood plasma. The calcium test measures the total calcium in the blood plasma. About half of this is tightly attached to the protein, albumin, which forms the bulk of the protein in your plasma. The calcium level that really counts is the ‘free’, or unbound, calcium that floats unattached in the plasma.
If you have low albumin levels, the total calcium in your blood will be less; however, because the amount attached to the albumin is reduced (because there is less albumin), the actual free levels of calcium may be fine (or even raised). Corrected calcium corrects the figure to give the actual, free amount of calcium.
Causes of low (corrected) calcium levels
Calcium levels are regulated by the kidney, thyroid and parathyroid glands, using the hormones parathyroid hormone, calcitonin and vitamin D. Low levels are uncommon. Causes include:
- Hypoparathyroidism (your parathyroid glands do not make enough of their hormone).
- Just after parathyroid surgery.
- Severe chronic kidney disease.
- Severe liver disease.
- Severe vitamin D deficiency.
- High phosphate ingestion (we can take in phosphate from enemas, from baby milks and from some flours – for example, chapati flour).
- Magnesium deficiency (often due to dietary deficiency and to prescribed medicines, including some antibiotics, diuretics and painkillers).
Causes of raised (corrected) calcium levels
- Primary hyperparathyroidism (overactive parathyroid glands) cause 8 out of 10 cases.
- Cancer of many different kinds can increase calcium levels, and accounts for about 2 out of 10 cases.
Rarer causes of hypercalcaemia include:
- Overconsumption of antacids.
- Pulmonary tuberculosis.
- Addison’s disease.
- Prolonged bed rest – especially in teenagers whose bones are growing fast.
- Vitamin A and/or D overdose.
- A number of medicines, including lithium, tamoxifen and diuretics.
- Kidney dialysis.
What do abnormal prothrombin time and INR mean?
Prothrombin time (PT) or International Normalised Ratio (INR) are sometimes measured as a part of standard liver function tests.
PT and INR are ways of measuring the ability of your blood to clot. Conditions which impair this clotting (prolonging the PT and increasing the INR) include:
- Acute and severe liver disease (including liver failure and severe paracetamol overdose).
- Use of anticoagulant medicines (in this case, lengthening the prothrombin time and increasing the INR is the intention).
How do I keep my liver function healthy?
There is a difference between what you need to do to keep your liver healthy most of the time and what you need to do if your liver is inflamed or damaged.
- If you are well, the way to look after your liver is with a balanced diet with a good fibre content, exercise, maintenance of a healthy weight, avoiding ‘fad’ diets (which can challenge the kidneys and liver hard), avoiding unnecessary medicines and supplements including paracetamol, stopping smoking, and staying within the recommended limits for alcohol (both daily and weekly). The liver does not need a detox diet, which will not help it and will often (if it is very low-calorie, for instance) make it work harder. The liver is a digesting, storage and detoxing organ.
- If your liver is inflamed and injured (for example, you have hepatitis and are jaundiced) or you have advanced liver disease (for example, cirrhosis) then, depending on the severity, you may be advised to have a special diet. This involves using carbohydrates as your major source of calories, eating fat moderately and cutting down on protein. You may be advised to take vitamin supplements, and if you are retaining fluid you should reduce your salt consumption to less than 1500 milligrams per day.
A few things to remember about abnormal liver function tests
- Liver function tests are not a diagnosis; they are a set of clues which help doctors make a diagnosis.
- Liver function tests are a sensitive early warning system for problems in the liver and, in some cases, elsewhere.
- Because ‘normal ranges’ used by laboratories are the levels between which about 19 out of 20 of people’s tests will fall, about 1 person in 20 will have an abnormal test without cause. About half of these people will have slightly high tests and about half will have slightly low tests, but their levels either way should not be extreme.
- The most likely cause of any particular pattern of abnormal liver function tests varies between patients (because of difference in age and gender) and between populations (because of variations in genetics and because different things are more common in different parts of the world).
- Almost any pattern of liver function test abnormality can be caused by medicines (including over-the-counter medications), by herbal remedies and traditional medicines from other cultures, and by poisonous substances.
- Many liver conditions cause no symptoms, at least at first; so, if you have several abnormal tests (or one test is markedly abnormal), it is very important to follow this up.
- Although single, mildly abnormal tests are not usually significant, any unexplained abnormality generally needs a check that you are well and may need a repeat test.
- Abnormal liver function tests in a person who is also sick are more worrying than those in a person who is well.
Canine liver enzymes-so many questions!
Sometimes increased serum liver enzyme activities occur because the patient does have primary hepatobiliary disease, but sometimes they are secondary to extrahepatic disease. And to confound results even more, tissues other than the liver also produce these enzymes. The liver plays a major role in the metabolism and excretion of drugs and exogenous and endogenous toxins, so it’s susceptible to injury from toxins and from diseases in other parts of the body. Plus, increased liver enzyme activities can occur from benign processes (e.g. hepatic nodular hyperplasia) or from conditions that are progressive and require early intervention for the best outcome (e.g. chronic hepatitis).
Performing extensive diagnostic evaluation, including liver biopsy, is costly and clients may be either reluctant or unable to proceed. It can be difficult to know how aggressively to work up these dogs. Dr. Lidbury says that if the cause of the elevated activity is a primary liver disease like chronic hepatitis or a liver tumor, the workup can escalate up to the need to perform a liver biopsy fairly quickly. Contrast that with extrahepatic causes. “Sometimes, especially for mild elevations in alkaline phosphatase (ALP), benign neglect may be the best course of action,” he says.
Through a logical, step-by-step approach, you can assess which dogs should be investigated for extrahepatic disease, which cases may need a liver biopsy, and which cases can be managed less aggressively.
Should I be checking ALT? AST? ALP? GGT?
Yes … but you should also know the enzymology behind all of these markers-where and why they’re produced-so you know how to interpret the laboratory results. “There are two big categories,” says Dr. Lidbury. “First, we have markers of hepatocellular damage. That would include alanine aminotransferase (ALT) and aspartate aminotransferase (AST). And then we have markers of cholestasis, ALP and gamma-glutamyltransferase (GGT).”
ALT is found primarily in the cytosol of hepatocytes. It’s released with increased cell membrane permeability or cell death. “Of all the liver enzymes, ALT is the most liver-specific,” says Dr. Lidbury. On rare occasions, ALT activity can be increased in patients with severe muscle injury. But, in general, ALT is considered a sensitive and specific marker of liver injury. “When hepatocytes die, then you get leakage,” Dr. Lidbury says. “ALT can also leak when you have just cell membrane damage. You don’t have to have necrosis for ALT to go up. Also, severe ALT increases don’t necessarily mean you have irreversible disease. Sometimes we misinterpret really high ALTs as irreversible disease and a poor prognosis. If you have a dog with acute liver injury, it might have a sky-high ALT, but if you can support the dog through that initial injury, then the disease could be reversible, and the liver can get back to normal. The liver has such great regenerative capacity.”
In dogs, aspartate aminotransferase (AST) is found in both the mitochondria and cytosol of hepatocytes. (In human hepatocytes, AST is mainly found in the mitochondria, and so, in people, it is a marker of severe liver damage.) The cytosolic fraction is released with increased cell membrane permeability or cell death, whereas the mitochondrial fraction is released only when there is hepatocyte necrosis. In general, increases in AST parallel those in ALT, but muscle disease can increase serum AST activity. Because of this, AST is considered to be less liver-specific than ALT. “At Texas A&M, we have actually taken AST off our basic chemistry panel because we feel it doesn’t add much information,” says Dr. Lidbury. A lot of the bigger reference labs still have it on their panels. It’s not un-useful; it usually just parallels the ALT.”
“So next we have that problem child-the ALP,” says Dr. Lidbury. “This is probably the least liver-specific and also the most commonly elevated liver enzyme. That is why it causes problems.” As you probably remember from pathophysiology units in veterinary school, there are different forms of ALP-hepatic, bone, renal, intestinal and steroid-induced ALP isoenzymes. They all may contribute to serum ALP activity in dogs. Dr. Lidbury says, however, “Luckily, when we measure ALP, we don’t have to worry about all of the isoforms because some of them aren’t actually measured by the assay. They have a trivial contribution to the overall activity of ALP in the serum, which is what the assay measures.” In the liver, ALP is bound to the membranes of the hepatocytes that form the bile canaliculi and the sinusoidal membranes. In cholestasis, the membrane-bound ALP is released into circulation and the synthesis of this enzyme is induced. ALP is considered a sensitive marker of cholestasis in dogs, but because of the other isoenzymes, ALP is not liver-specific.
“I don’t tend to take ALP quite as seriously as increases in ALT,” Dr. Lidbury says. “Sometimes they’re not actually that clinically significant, if they’re mild and the dog doesn’t have other signs going on. Sometimes this is a case where benign neglect may be the best course of action, but not always. Obviously, if ALP didn’t tell us anything, we wouldn’t measure it. There is a nuance; it depends on looking at the whole case.”
So, what can cause increased ALP activity? Dr. Lidbury answers, “If you look in textbooks, there’s a long list with about 30 to 40 reasons. But in terms of big categories, causes of increased ALP can be hepatic disease such as nodular hyperplasia (a very common, completely benign cause of increased ALP in older dogs), vacuolar hepatopathy (common with Cushing’s disease), toxins, chronic hepatitis, neoplasia, biliary tract disease (such as a gallbladder mucocele) and extrahepatic disease (such as pancreatitis).”
Serum ALP activities can be increased when there is increased osteoblast activity, such as in growing dogs, or when the dog has an osteolytic disease, such as osteosarcoma. The steroid-induced ALP isoenzyme can be induced by both exogenous and endogenous glucocorticoids. Dr. Lidbury warns, “Steroid-induced isoenzyme is really important because it can be iatrogenic. Asking the owner whether the dog is on any steroids or whether they’re using any steroid hand creams themselves, that kind of thing, is very important.”
Gamma-glutamyltransferase (GGT) is bound to the hepatocytes in the bile canaliculi and bile ducts. Increases in serum GGT activity generally parallel those in ALP. Both GGT and ALP are considered sensitive markers of cholestasis. Dr. Lidbury says, however, “GGT can’t differentiate between intrahepatic and extrahepatic cholestasis. You’d think since it’s a bit further down the biliary tract, that it might. But, unfortunately, it doesn’t do that.” In general, increases in GGT are considered to be less sensitive but more specific for the presence of hepatobiliary disease than those of ALP.
The pattern of liver enzymes
Dr. Lidbury confirms that looking at patterns of liver enzymes can be useful (Table 1). “For example, if you have a dog where your ALP is 10X the upper limits of normal and your ALT is increased to twice the upper limits of normal, we’d say that dog has a cholestatic pattern,” he says. “So, we’d be thinking about diseases that cause intra- or extra-hepatic cholestasis. If you have the opposite situation, and a dog has an ALT that is 10X the upper limits of normal and the ALP is only very modestly increased, then that’s more of a hepatocellular damage pattern. That makes you think of things like chronic hepatitis or toxins. Sometimes you get genuinely mixed patterns, and you can’t differentiate the two. But you can often get some clues.”
Table 1: Typical patterns of clinicopathological changes associated with liver disease in dogs
Acute hepatitis/hepatic necrosis
Congenital portosystemic shunt
Biliary tract obstruction
Non-obstructive biliary tract disease
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ALT-serum alanine transaminase activity
ALP-serum alkaline phosphatase activity
SBA-serum bile acid concentration
N-within the reference interval
What can the patient history and exam tell me?
Since there are so many causes of increased liver enzyme activities, Dr. Lidbury says the key is to narrow the list of all possible causes down to those that are probable for a patient on that day. The patient history and physical examination are often helpful in doing this. The patient’s signalment can help refine the differential diagnosis list. See Table 2 for known age and breed predispositions for certain liver conditions.
Table 2. Signalment to refine the differential diagnosis list for hepatic injury
Very young dogs are more likely to suffer from congenital conditions (e.g. congenital portosystemic shunts) or infectious diseases (e.g. infectious hepatitis), rather than neoplasia or inflammatory conditions, such as chronic hepatitis.
Copper-associated chronic hepatitis
West Highland white terriers
Idiopathic chronic hepatitis
Congenital portosystemic shunts
When taking a patient’s history, be sure to ask the client specifically about exposure to hepatotoxins such as cycads (including the sago palm), blue green algae, Amanita mushrooms, aflatoxins, heavy metals, xylitol or chlorinated compounds. Drugs that can be hepatotoxic include ketoconazole, azathioprine, carprofen, lomustine, acetaminophen, mitotane, phenobarbital and various antimicrobial agents.
“Asking specifically about nutraceutical and herbal remedies is important, especially in this situation, because there are quite a few herbal remedies that are known to have the potential to cause liver injury in dogs,” Dr. Lidbury says. Those include herbal teas, pennyroyal oil and comfrey.
Checking the dog’s vaccination history is also important because leptospirosis and canine adenovirus-1 can cause hepatic injury.
Early in the course of liver disease, a dog may not have any or nonspecific findings or clinical signs such as vomiting, diarrhea, weight loss, polyuria/polydipsia and hyporexia. Dr. Lidbury admits that these are not very helpful signs since so many different diseases can cause them. “But certainly, if you have a dog with increased liver enzymes and that kind of clinical sign, then that may make you a little more aggressive about how you approach that dog,” he says. He says it’s also important to remember that dogs with hepatobiliary disease don’t always display clinical signs or have abnormal physical examination findings.
Certain exam findings suggest an extrahepatic disease is causing increased liver enzyme activities. For example, polyphagia is consistent with diabetes mellitus or hyperadrenocorticism and bilateral symmetric alopecia is consistent with hypothyroidism or hyperadrenocorticism. Physical examination findings consistent with hepatobiliary disease include icterus, ascites, poor body condition, stunted growth, hepatomegaly or signs of hepatic encephalopathy. When any of these clinical signs are present, you will want to investigate further.
What clues can other lab tests provide?
Other changes on a serum chemistry profile can provide clues about the cause of increased serum liver enzyme activities. “You can look for signs of liver dysfunction,” Dr. Lidbury says. “Things the liver produces-albumin, cholesterol, glucose, and blood urea nitrogen (BUN)-can be decreased with liver disease or decreased hepatic function. And bilirubin can be increased.”
Dr. Lidbury warns, “It’s definitely possible to have serious liver disease and have all of those things completely normal. The liver has this large reserve capacity. That’s a really good thing for the body, but it makes our life a bit harder when we’re trying to diagnose liver disease.” It’s important to remember that these changes are not specific for hepatobiliary disease. For example, the serum bilirubin concentration may also be increased when there is hemolysis.
Dr. Lidbury offers this helpful tip: “When we look at a chemistry panel, especially when we’re in a rush on a busy day in the clinic, we tend to look for things that are flagged. You go down the list of 10 to 15 analytes and look for things that are high or low. You can miss things doing that. Some of these numbers are in the normal range, but at the low end of normal. If several things are like that, it can give you an impression that the liver is not working so well. So, try to slow yourself down and actually look at the numbers. Really read them.”
Patterns of serum liver enzyme activities can suggest certain pathologies. For example, during cholestasis, ALP activity is dramatically increased and is higher than ALT activity. There may also be evidence of extrahepatic diseases. A complete blood count (CBC) can suggest inflammatory disease or rule out hemolysis. If the CBC shows microcytosis, that’s consistent with portosystemic shunting (or iron deficiency).
Dr. Lidbury also recommends conducting a urinalysis (UA). “Usually you can justify doing a UA whenever doing a chemistry panel. It just allows you to fully interpret that chemistry panel.” He notes that urine specific gravity can be decreased in patients with hepatic insufficiency or portosystemic shunts. Excessive bilirubinuria in dogs implies hemolytic or hepatobiliary disease. Urate urolithiasis seems to be more common in patients with portosystemic shunts than those with other types of hepatic dysfunction, but urate crystalluria is not specific for hepatobiliary disease.
When should I do more testing?
Once you have completed a basic evaluation of a dog, you have to decide whether to pursue further diagnostic testing. “It’s hard to make hard and fast rules about when you should take things further. Every case is different,” says Dr. Lidbury. “So what I offer are more guidelines than rules.”
Dr. Lidbury’s guidelines:
If clinical findings or other laboratory test results suggest primary hepatobiliary disease, pursue further diagnostic testing.
If clinical findings or laboratory test results suggest extrahepatic diseases are the cause of increased liver enzyme activities, further diagnostic evaluation to identify the underlying disease is needed.
If serum liver enzyme activities (ALP or ALT) are severely (three times the upper limit of the reference range) or persistently increased (greater than twice the upper limit of the reference range for more than three to four weeks), further diagnostic evaluation is needed.
Because ALT is more liver-specific than ALP, increases in serum ALT activity are more concerning or worrisome than increases in ALP.
If none of these conditions apply, then it is reasonable to wait and recheck the serum liver enzymes later.
What comes after a chemistry panel, CBC and UA?
Dr. Lidbury’s advice: “Next we may want to do some bile acid tests. Ammonia has some utility, but it’s more limited and not every practice has the capability to measure ammonia. It seems to be affected a bit more by other variables, too.” He says that measurement of plasma ammonia and paired preprandial/postprandial bile acids are sensitive tests for portosystemic shunting, and he recommends performing one of these tests when a portosystemic shunt is suspected. Because of the hepatic functional reserve capacity, these tests are not as sensitive in detecting hepatic insufficiency (in the absence of shunting). “Remember that dogs can have these normal liver function tests and still have significant liver disease,” Dr. Lidbury says. Also, performing these tests does not always change the decision about whether to perform a liver biopsy.
Radiography. “Plain radiographs are useful for things like assessing the general size and shape of the liver,” says Dr. Lidbury. “You can perhaps see masses or maybe extrahepatic disease, like a foreign body in the GI tract. But radiographs rarely lead to a definitive diagnosis of liver disease.”
Abdominal ultrasonography. This form of imaging is more useful than radiography for evaluating the hepatic parenchyma and the biliary tract. “The biliary tract is quite a hard area to image. Sometimes you’ll get a definitive diagnosis, like a gallbladder with a typical ‘sliced kiwi fruit’ appearance of a gallbladder mucocele,” says Dr. Lidbury. “But sometimes ultrasound doesn’t give us a definitive diagnosis. We may see nonspecific changes like an enlarged liver or a small liver with a slightly abnormal echo texture. You may also have a very boring, completely normal ultrasound and still have chronic hepatitis going on. A normal ultrasound doesn’t rule out severe liver disease. That’s important to bear in mind.” Unless a disease leads to architectural changes in the hepatobiliary system, a definitive diagnosis can’t be made with ultrasonography. Despite this limitation, Dr. Lidbury says that when primary hepatic disease is suspected, abdominal ultrasonography is usually performed before liver biopsy.
Scintigraphy. Dr. Lidbury says scintigraphy is being used less frequently-they rarely use the technique at Texas A&M. “It involves injecting a radioactive isotope, which is why people didn’t like to do it. It’s a very good test for portosystemic shunting. But it doesn’t tell you whether the shunt is intrahepatic or extrahepatic.”
CT and MRI. Dr. Lidbury says that cross-sectional imaging is being used more often for assessing abdominal disease in dogs. Computed tomography (CT) is used most often because it’s quick and a bit cheaper than magnetic resonance imaging (MRI). “Obviously not everybody is going to be able to do this at the moment. But who knows? Maybe in 20 years, every practice will have a micro-CT scanner rather than an x-ray unit,” ponders Dr. Lidbury. “It’s a nice way to look for congenital portosystemic shunts. And it’s quite good if you’ve got a big liver mass. Surgeons like to look at these CTs before they decide if they will try to resect a mass or not.”
“Cytology-this can definitely be useful. But I don’t do it in every case,” says Dr. Lidbury. “I pick my cases. It’s relatively easy to do. You just need ultrasound guidance. It’s pretty safe and quite cheap, too.” Hepatic cytology can lead to a definitive diagnosis of certain diseases, such as lymphoma, and can be highly suggestive for the presence of others. You may wish to perform cytology when you suspect a round cell tumor is present, when you suspect infectious agents (e.g. Histoplasma capsulatum) and when hepatic masses are visible with ultrasonography. “Cytology allows us to look at the cells, but it doesn’t allow us to see how those cells are actually arranged in their architecture. Because of that, there are some conditions-like chronic hepatitis-that you can’t diagnose cytologically.”
When should I biopsy the liver?
To make a definitive diagnosis of primary hepatic disease, a liver biopsy is often required. “This is kind of the last step in the diagnostic workup,” says Dr. Lidbury. “It’s quite an invasive and expensive technique.” Click here (or on the image) to download a flowchart showing how Dr. Lidbury suggests approaching the decision about whether to perform a liver biopsy on a particular patient.
Before doing a biopsy, Dr. Lidbury recommends assessing the dog’s risk of hemorrhage by measuring prothrombin and activated partial thromboplastin time, ideally measuring serum fibrinogen concentration, and performing a platelet count. He also usually does a buccal mucosal bleeding time.
The three types of liver biopsy techniques in dogs are percutaneous needle biopsy, laparoscopic biopsy and surgical biopsy. Each technique has advantages and disadvantages. See Table 3 for a comparison of the three techniques. Dr. Lidbury says, “All of them are valid ways to get liver biopsies. It just depends on what you have available and how comfortable you feel. Sometimes it’s a bit about the patient, too.”
Table 3. A comparison of liver biopsy techniques
Percutaneous needle biopsy
Size of biopsy specimen
Hospitalization or postoperative care required?
No hospitalization required
Patient is usually discharged same day
Patient may need to be hospitalized; incision requires postoperative care
Ability to control hemorrhage
Least ability to control; if bleeding occurs, may need to perform exploratory surgery to control
Can apply pressure or gel foam to area of hemorrhage through laparoscopic incisions
Direct visualization allows surgeon to control bleeding
Special equipment required, which translates to increased cost for client
Visualization of liver and surrounding area is best of three techniques; simple procedure to perform
No matter which technique is chosen, it’s important to collect multiple biopsy samples. Dr. Lidbury advises, “I’d keep part of the biopsy specimens back for aerobic and anaerobic culture and copper quantification. When you get the pathology report back and it says there are bacteria, or they suspect it’s copper, you’re going to regret it if you have thrown everything into formalin.”
“Again, it is hard to make universal rules about when to perform a liver biopsy, because every case is different,” he says. But when you suspect primary hepatic disease, he advises that it’s better to go ahead and do the biopsy rather than delay until the dog is in end-stage liver failure, at which point treatment will probably be ineffective.
> Alvarez L, Whittemore J. Liver enzyme elevations in dogs: diagnostic approach. Compend Contin Educ Vet 2009;31(9):416-418.
> Cooper J, Webster CL. The diagnostic approach to asymptomatic dogs with elevated liver enzyme activities. Vet Med 2006:101(5):279-284.
> Lidbury JA, Steiner JM. Diagnostic evaluation of the liver. In: Canine & feline gastroenterology. 1st ed. St. Louis: Elsevier Saunders, 2013;863-875.
About the speaker: Jonathan Lidbury, BVMS, MRCVS, PhD, DACVIM, DECVIM, is an assistant professor in the Department of Veterinary Small Animal Clinical Sciences at Texas A&M University in College Station, Texas. He is interested in all areas of small animal gastroenterology and is working to develop new noninvasive tests for liver disease in dogs.
Liver Enzyme – an overview
Liver enzymes, such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT), are the most sensitive indicators of hepatocyte injury. Both AST and ALT are normally present in low concentrations. However, with cellular injury or changes in cell membrane permeability, these enzymes leak into circulation. Of the two, the ALT is the more sensitive and specific test for hepatocyte injury as AST can be also elevated in the state of cardiac arrest or muscle injury. Serum glutamate dehydrogenase (GLDH) is also a marker and is elevated in the state of severe hepatic damage. Serum alkaline phosphatase (ALKP) provides an elevation of the patency of the bile channels at all levels, intrahepatic and extrahepatic. Elevation is demonstrated in patients with obstruction of the extrahepatic biliary tract or caliculi. In general, serum levels are elevated in hepatobiliary disease.106
As mentioned earlier liver damage occurs after a thermal injury. The elevation of hepatic enzymes correlates with the severity and extend of the hepatic injury. Small hepatic injury leads to a predominantly elevation of the cytoplasmatic enzymes ALT and only little elevation of AST. The so-called de Ritis ratio GOT/GPT <1. In a state of severe hepatic damage, mitochondrial bound enzymes are strongly elevated and the de Ritis ratio GOT/GPT >1 (Table 26.3).106
Thermal injury causes liver damage by edema formation, hypoperfusion, pro-inflammatory cytokines or other cell death signals with the release of the hepatic enzymes. Others and we have shown that serum AST, ALT and ALKP are elevated between 50 to 200% when compared with normal levels (Figure 26.9). We observed that serum AST and ALT peaked during the first day postburn and ALKP during the second day postburn. During hepatic regeneration all enzymes returned to baseline between 10–14 days postburn. If liver damage persists, enzymes stay elevated. There is no need for therapeutic intervention to decrease elevated enzymes. Enzymes can only be used as markers and the effect of therapeutics can be studied.
What Does it Mean if a Dog has Elevated Liver Values? • MSPCA-Angell
By Mara Ratnofsky, DVM
The liver is an amazing organ which carries out over 500 life-sustaining functions. It processes all of the blood leaving the gastrointestinal tract – breaking down toxins, converting medications into forms that can be better used by the body, and creating nutrients. The liver stores energy and iron for future use by the body, helps regulate blood clotting, and clears old red blood cells from circulation. The liver secretes its waste products in the form of bile, a substance which also aids in the digestion of fats.
Your veterinarian may recommend a blood test to check your dog’s liver values. This may be part of a routine screen to get a more complete picture of your dog’s overall health, or your vet may have concerns about your dog’s liver function. Poor appetite, vomiting, lethargy, increased drinking and urination, yellow discoloration of the eyes or skin, seizures, and fluid build-up in the abdomen can all be signs of liver disease.
Below is a breakdown of what your vet is evaluating when he or she looks at “liver values.”
1) Hepatocellular Enzymes – AST (aspartate aminotransferase) and ALT (alanine aminotransferase)
AST and ALT are enzymes contained within liver cells. When levels are increased in the blood, it means that the enzymes have leaked out of the liver cells due to cell damage. AST is found in muscle cells as well as liver cells, so an elevation in AST without a similar elevation in ALT may indicate muscle damage rather than liver damage. Although ALT elevations are specific for liver, there are many non-liver diseases that can indirectly affect the liver and cause increases in ALT. For example, heart failure and intestinal inflammation can cause an increase in ALT up to 4 or 5 times the normal range. Even severe dental disease can cause an elevation in ALT. In terms of primary liver issues, ingestion of certain toxins or chronic inflammation of the liver (due to infection, an over-reaction of the immune system, genetic disorders, etc.) tend to create the most significant ALT elevations.
2) Cholestatic Enzymes – ALP (alkaline phosphatase) and GGT (γ-glutamyl transpeptidase)
ALP and GGT are contained in the cells that line the bile ducts – thin tubes that guide the flow of bile from the liver to the small intestine. If bile flow is blocked, these cells increase production of ALP and GGT and release them into the blood. Causes of poor bile flow within the liver include nodular hyperplasia (a benign condition of older dogs), overwhelming infection, cancerous tumors, and blood vessel abnormalities. However, there are several different forms of ALP in the dog and our routine laboratory tests can’t differentiate between them. Dogs under a year old usually have an elevated ALP as a result of bone growth, as there is a form of ALP associated with bone (B-ALP). Dogs taking steroid medication often have an elevated ALP because there is a form stimulated by the presence of steroids (C-ALP). These elevations are not indicative of liver dysfunction. Certain dog breeds, such as Scottish terriers, Siberian huskies, and miniature Schnauzers, also tend to have benign elevations in ALP. And just as with the hepatocellular enzymes, the cholestatic enzymes will also increase due to the effect of non-liver diseases on the liver. Pancreatitis, gall bladder disease, intestinal inflammation, and certain endocrine diseases all increase ALP.
Other routine lab results can also help us identify liver disease. Since the liver is responsible for making albumin (a blood protein) and cholesterol, a low albumin or low cholesterol level might be the result of severe liver disease. Yellowing of the eyes and skin, also known as jaundice or icterus, can occur when the liver is not effectively removing broken-down old red blood cells from circulation. Low blood sugar can result when a diseased liver is not able to release its stored energy.
As you can see, an elevation in liver values doesn’t necessarily mean there is a serious problem with your dog’s liver. Your veterinarian will take into consideration your dog’s breed, age, medical history, as well as recent medications and additional lab results, to determine if there is a benign explanation for the lab results, if monitoring liver values for several months is appropriate, or if further diagnostics are warranted. Additional diagnostics might include x-rays, an abdominal ultrasound, more blood tests (bile acids, ammonia level), or liver biopsy. In any case, the liver has an amazing capacity to regenerate, so the presence of even significantly elevated liver values doesn’t necessarily mean a poor prognosis.
Liver blood tests: how to interpret abnormal results | Implementing guidelines
Read this article to learn more about:
- when to request liver blood tests and how to interpret the results
- actions to take if results of liver blood tests are abnormal
- approaches to common conditions, including non-alcoholic fatty liver disease.
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For many major causes of death, including chest, neoplastic, and vascular disease, mortality is falling.1 However, deaths due to liver disease are rising rapidly; between 1970 and 2010 the UK standardised mortality rate for liver disease increased by over 400%.1 The mortality rate for patients under 65 years of age increased by almost 500% over the same period,1 and liver disease is now the fifth most prevalent cause of premature death in England and Wales.2
Liver disease in adults has three major causes: alcohol misuse; chronic viral hepatitis; and obesity/metabolic syndrome, which may lead to non-alcoholic fatty liver disease (NAFLD).3 Much liver disease is preventable and if it is diagnosed early, clinical interventions and lifestyle changes may slow or stop disease progression.3
In its early stages, liver disease is often asymptomatic—approximately 50% of patients with cirrhosis are first diagnosed when admitted to hospital with a decompensating event, such as ascites, bleeding varices, or hepatic encephalopathy.4
Primary care has a major role to play in the prevention and early detection of liver disease, and liver blood tests are an important aspect of this. In November 2017, the British Society of Gastroenterology (BSG) published Guidelines on the management of abnormal liver blood tests. The guideline is designed to be used in both primary and secondary care and includes recommendations on:3
- what constitutes an abnormal liver blood test
- how to respond to abnormal liver blood test results
- when liver blood tests should be performed
- what comprises a standard liver blood test panel.
Although traditionally referred to as liver function tests (LFTs), typical testing panels include measurement of hepatobiliary enzymes in addition to true measures of liver function. For this reason, the BSG guidance refers to liver blood tests rather than LFTs to capture more accurately the relevance to clinical practice.3
The need for guidance
There is no standardised panel for liver blood tests and testing varies between hospitals.3
Liver blood tests can be a challenge to interpret; results may be normal or near normal even in advanced liver disease, and, when abnormal, the degree of abnormality may not reflect disease severity—liver blood tests may be abnormal even when there is no significant liver disease.3 Standard liver blood test panels may be used routinely when patients have unexplained or non-specific symptoms and in these circumstances abnormal results are found in around 20% of patients.5 The significance of these results is often unclear and patients are frequently subject to further cycles of investigation, yet most patients referred to hospital with abnormal liver blood tests do not have significant liver disease.5
When to perform liver blood tests
Liver disease can develop with few signs or symptoms, but using liver blood tests to investigate non-specific symptoms that may indicate liver disease, such as anorexia, fatigue, or nausea, may identify a hepatic condition that can be effectively treated.3 Using routine liver blood tests to investigate vague symptoms that do not point to possible liver disease may not be clinically helpful.
Evidence of chronic liver disease
Liver blood tests, including international normalised ratio (INR), should be used to assess and monitor liver function in patients who have symptoms or signs of cirrhosis, portal hypertension, or liver failure. Signs and symptoms include ascites, peripheral oedema, spider naevi, and hepatosplenomegaly.3
Conditions associated with a risk of developing liver disease
Patients with other autoimmune diseases are known to be at increased risk of developing autoimmune liver disease. Liver blood tests may, therefore, be appropriate if patients with autoimmune diseases develop symptoms that suggest liver disease, such as pruritus in primary biliary cholangitis.3
Additionally, patients with inflammatory bowel disease have just under a 10% risk of developing primary sclerosing cholangitis and should be considered for liver blood test monitoring.3
Use of hepatotoxic drugs
Because a wide variety of drugs have been associated with liver disease, liver blood tests may be recommended to monitor liver function in patients prescribed certain medications such as carbamazepine, methyldopa, minocycline, macrolide antibiotics, nitrofurantoin, statins, sulphonamides, terbinafine, chlorpromazine, and methotrexate.3
Although statins can lead to drug-induced liver injury this is rare, and studies have demonstrated that statins are generally suitable for use in patients with pre-existing abnormal liver enzymes.3
Family history of liver diseases
Patients who have relatives with familial diseases, including haemochromatosis or Wilson’s disease, should be screened for these conditions with relevant tests.3
Liver enzymes are of little value in assessing the extent of alcohol misuse, and are a poor guide to the development of progressive fibrosis in alcohol-related liver disease (ARLD). Elevated enzymes may, however, be useful in motivating behaviour change, with elevated gamma-glutamyltransferase (GGT) being the best predictor of mortality.3 NICE Guideline (NG) 50 on Cirrhosis in over 16s: assessment and management recommends screening for cirrhosis using transient elastography in patients who have been drinking at harmful levels (in excess of 50 units per week and 35 units per week for men and women, respectively) for several months.6
Chronic viral hepatitis may be associated with non-specific symptoms, including fatigue, but most patients are symptom-free. Tests for hepatitis B and/or hepatitis C are recommended when risk factors are identified and as part of a liver aetiology screen when liver blood tests are abnormal. Risk factors for hepatitis include:3
- birth or upbringing in a high-prevalence country
- a history of injecting drugs
- close household contact with someone with viral hepatitis
- time spent in prison.
Risk factors for non-alcoholic fatty liver disease
Normally suspected following abnormal liver blood tests or an echobright liver on ultrasound scan, non-alcoholic fatty liver disease (NAFLD) is, in part, a diagnosis of exclusion. When fatty change is seen on ultrasound, other causes including alcohol misuse and viral hepatitis, should be considered.3 NICE Guideline 49 on Non-alcoholic fatty liver disease (NAFLD): assessment and management recommends that liver bloods tests should not be used to rule out NAFLD in those with risk factors such as obesity and metabolic syndrome.7
Interpreting test results
The BSG guidelines3 include information on a range of different liver blood tests, providing guidance on how test results should be interpreted and making recommendations for further investigations that may be appropriate.
Most laboratories report total bilirubin, which will be raised by an elevation of either the conjugated or the unconjugated form. In adults, the most likely cause of an isolated raised unconjugated bilirubin, once haemolysis has been excluded, is Gilbert’s syndrome—an inherited metabolic disorder characterised by impaired conjugation, which is not associated with liver disease.3 Raised conjugated bilirubin is seen in obstruction of the hepatobiliary system or in parenchymal liver disease, such as hepatitis from any cause or advanced cirrhosis.3
Interpretation of hyperbilirubinaemia in neonates and infants requires specialist support because of the risk of kernicterus and the need to diagnose with urgency conditions such as biliary atresia.8
Albumin is a protein synthesised by the liver that can serve as a marker of synthetic liver function. Albumin concentration may, however, be reduced in other clinical situations, including sepsis, systemic inflammatory disorders, nephrotic syndrome, malabsorption, and gastrointestinal protein loss.3
Alkaline phosphatase (ALP) is predominantly a liver enzyme but is also found in bone and in smaller quantities in the intestines, kidneys, and white blood cells. Levels of ALP are higher in childhood and in pregnancy, where it is associated with bone growth and placental production, respectively.3 Consequently, pathologically increased levels of ALP may be found not only in cholestatic liver disease (e.g. common bile duct obstruction, intrahepatic duct obstruction [including by metastases], primary biliary cholangitis, primary sclerosing cholangitis, and drug-induced cholestasis) but also in bone disease (metastatic bone disease, vitamin D deficiency, Paget’s disease, and bone fractures). Raised ALP may also result from cholestasis caused by hepatic congestion due to right-sided heart failure.3
If ALP is elevated in isolation, measurement of GGT (see below) can help to provide some indication as to whether or not the origin is hepatic, and, if doubt remains, electrophoresis can be used to differentiate hepatic from non-hepatic ALP.3
Aspartate aminotransferase and alanine aminotransferase
Elevated levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are the most common abnormalities seen in liver blood tests. Both AST and ALT are enzymes present in hepatocytes that are released into the blood following hepatocyte injury or death.3 Alanine aminotransferase is present at low concentrations in non-hepatic tissue and elevations that are not liver-related are uncommon. In contrast, AST is present in cardiac, smooth, and skeletal muscle and may be elevated in myocardial infarction or myositis. Although AST is not as liver-specific as ALT, it may be a more sensitive indicator of liver cell injury.3
In children, creatine kinase measurement may help to determine whether an isolated rise in either of these two enzymes is due to an underlying skeletal muscle disorder, such as muscular dystrophy.3
Abundant in the liver and also present in the intestines, kidneys, pancreas, and prostate, but not in bone, GGT can be useful in determining whether elevated ALP is of bone or liver origin. Levels of GGT may be elevated by factors that are not liver-related, including obesity, excess alcohol consumption, and certain drugs. In spite of this low specificity, GGT is one of the best predictors of mortality in liver disease.3
As ALP is not a reliable indicator in children, GGT can be used to establish the likelihood of biliary disease, for example congenital abnormalities of the biliary tract and genetic disorders of bile metabolism.3
Prothrombin time (PT) and international normalised ratio (INR) are measures of blood clotting. Clotting factors are synthesised in the liver and, when there is significant liver damage (usually >70% loss of synthetic function), their production is reduced, which may be demonstrated by prolonged PT or INR. Prolonged PT or INR can, therefore, indicate acute or chronic liver dysfunction, but can also be caused by vitamin K deficiency in fat malabsorption and chronic cholestasis.3
Platelet reduction is an indicator of advanced liver disease, although platelets may be reduced in a wide variety of medical conditions. In liver morbidity, platelet reduction is associated with splenic enlargement secondary to portal hypertension with consequent platelet sequestration; a reduction in thrombopoietin levels; and reduced platelet production.3
Abnormal test results
When results of liver blood tests are abnormal, the clinical response should include: obtaining a thorough clinical history; performing examinations; and, in appropriate patient groups, considering primary sclerosing cholangitis and viral hepatitis (see Box 1 and Figure 1).3
Box 1: Clinical responses to abnormal liver blood tests
- Obtain a thorough clinical history, including:
- country of birth
- any liver-related symptoms, such as abdominal pain, jaundice, pruritus, weight loss, etc
- presence of co-morbidities (e.g. heart failure, autoimmune conditions, inflammatory bowel disease, malignant disease) and features of metabolic syndrome, such as central obesity, hypertension, diabetes/insulin resistance, and dyslipidaemia
- use of any prescribed, over-the-counter, herbal, illicit, or injected drugs
- recent travel
- tick bites
- muscle injury
- alcohol history
- family history—
- in children this should include maternal, neonatal, nutritional, and developmental history
- Perform an examination, considering:
- body mass index
- other signs of chronic liver disease
- Consider hepatitis A, hepatitis E, and cytomegalovirus infection if marked elevation of ALT (>1000 U/litre)
- In patients with raised cholestatic liver enzymes and either a personal or family history of autoimmune disease or a personal history of inflammatory bowel disease consider primary sclerosing cholangitis.
Approaches to common conditions
Non-alcoholic fatty liver disease
Non-alcoholic fatty liver disease is most commonly suggested by an echobright liver on ultrasound and other causes of fatty changes in the liver, including alcohol misuse, must be excluded in order to establish the diagnosis.3
Once NAFLD has been diagnosed, the BSG guideline recommends screening for advanced fibrosis using a non-invasive, algorithm-based assessment that brings together serum and other biomarkers. Examples include Fibrosis-4 (FIB-4) or NAFLD fibrosis score (NFS).3 NICE Guideline 49 recommends considering the enhanced liver fibrosis (ELF) test for this purpose.7
Patients with NAFLD who do not have advanced fibrosis can be managed in primary care, with treatment focusing on:3
- long-term weight loss through reduced calorie intake and increased physical activity
- management of co-morbidities, including diabetes, dyslipidaemia, and hypertension.
Where tests indicate advanced fibrosis the patient should be referred to a hepatologist.3
Alcohol-related liver disease
Alcohol-related liver disease is the most common cause of liver-related mortality in western populations. Most patients with ARLD drink heavily, but ARLD is not limited to those who are dependent on alcohol. A relationship also exists with obesity—the risk of liver disease doubles for any given alcohol intake when body mass index exceeds 35 kg/m2.3
Prevention and treatment of ARLD is focused on helping patients to stop drinking harmfully.3 Brief alcohol interventions in primary care are effective at lower levels of alcohol misuse, but those who are unable to address their drinking or who are dependent on alcohol should be referred to alcohol services.
Primary care clinicians have an important role in the prevention, early diagnosis, initial investigation, and referral of patients with liver disease. There are, however, challenges associated with this, including:
- the large number of patients with risk factors for developing liver disease
- limited time available for GPs and practice nurses
- lack of confidence in delivering brief interventions for alcohol and obesity
- availability of referral pathways for patients who misuse alcohol or who are obese
- investigations, including ELF and transient elastography testing, being difficult to access.
Appropriate use of liver blood tests can support early diagnosis and the identification of risk factors for liver disease. This in turn enables the use of early interventions to stop liver disease developing, or prevent early liver disease progressing to cirrhosis. The BSG guidance on liver blood tests provides recommendations on choosing appropriate liver blood tests, interpreting the results, and subsequent actions, which it is hoped will support the important role of primary care in preventing and identifying liver disease. For sources of further information, see Box 2.
Box 2: Information for patients, carers, and practitioners
- As part of the Liver disease priority programme, the British Liver Trust and Royal College of General Practitioners are working in partnership to develop a toolkit containing information and resources for GPs, practice nurses, and patients, which is available at: www.rcgp.org.uk/clinical-and-research/toolkits/liver-disease-toolkit.aspx
- The website of the British Liver Trust (www.britishlivertrust.org.uk) also provides comprehensive information both for healthcare professionals and for patients with liver disease.
Dr Jez Thompson
RCGP/British Liver Trust Clinical Champion for Liver Disease Clinical Director, Bevan Healthcare
After reading this article, ‘Test and reflect’ on your updated knowledge with our multiple-choice questions. Earn 0.5 CPD credits.
- Liver blood tests may be normal even in advanced liver disease and are not infrequently abnormal in the absence of liver disease:
- interpreting liver blood tests in isolation may be ineffective in diagnosing or excluding liver disease
- Investigation of non-specific symptoms that may indicate liver disease, such as fatigue, nausea, or anorexia, may lead to identification of a hepatic condition that can be effectively treated
- Using liver blood tests to investigate vague symptoms that do not point to possible liver disease may not be clinically helpful
- Liver enzymes are a poor guide to the development of alcohol-related liver disease but, if elevated, can be useful in promoting behaviour change
- NAFLD is most commonly suggested by fatty change seen on ultrasound scan and investigation must include exclusion of other causes, including alcohol misuse
- Primary care has an important role in the prevention, early diagnosis, initial investigation, and referral of patients with liver disease, and appropriate use of liver blood tests can support this.
NAFLD=non-alcoholic fatty liver disease
written by Dr David Jenner, GP, Cullompton, Devon
- Abnormal liver blood test results are commonly encountered in primary care and can be important markers of serious liver disease
- Commissioners should agree local pathways—based on the tables and advice in the BSG guidance—for the investigation and management of liver disease and abnormal liver blood tests
- Local algorithms for the investigation and management of NAFLD should be published on local referral guideline sites
- Practices could incorporate the specified blood tests from the pathway into templates on their clinical software systems
- Awareness in primary care of the FIB-4 and NFS screening tests is low; these tests could be included on the pathway site or on primary care clinical systems, ideally where the required pathology results are autopopulated from the notes (as for QRISK®).
BSG=British Society of Gastroenterology; NAFLD=non-alcoholic fatty liver disease; FIB-4=fibrosis-4; NFS=NAFLD fibrosis score
- Williams R, Aspinall R, Bellis M et al. Addressing liver disease in the UK: a blueprint for attaining excellence in health care and reducing premature mortality from lifestyle issues of excess consumption of alcohol, obesity, and viral hepatitis. Lancet 2014; 384 (9958): 1953–1997.
- British Liver Trust website. Facts about liver disease. www.britishlivertrust.org.uk/about-us/media-centre/facts-about-liver-disease/ (accessed 15 January 2018).
- Newsome P, Cramb R, Davison S et al. Guidelines on the management of abnormal liver blood tests. Gut 2018; 67 (1): 6–19.
- Ratib S, Fleming K, Crooks C et al. 1 and 5 year survival estimates for people with cirrhosis of the liver in England, 1998–2009: a large population study. J Hepatol 2014; 60 (2): 282–289.
- Donnan P, McLernon D, Dillon J et al. Development of a decision support tool for primary care management of patients with abnormal liver function tests without clinically apparent liver disease: a record-linkage population cohort study and decision analysis (ALFIE). Health Technol Assess 2009; 13 (25): iii–iv, ix–xi, 1–134.
- NICE. Cirrhosis in over 16s: assessment and management. NICE Guideline 50. NICE, 2016. Available at: www.nice.org.uk/ng50
- NICE. Non-alcoholic fatty liver disease (NAFLD): assessment and management. NICE Guideline 49. NICE, 2016. Available at: www.nice.org.uk/ng49
- Children’s Liver Disease Foundation website. Biliary Atresia. Available at: www.childliverdisease.org/information/medical-stuff/information-on-liver-diseases/biliary-atresia (accessed 15 January 2018).
90,000 LDH (Lactate dehydrogenase, L-lactate: NAD + Oxidoreductase, Lactate dehydrogenase, LDH)
What is LDH (Lactate dehydrogenase, L-lactate: NAD + Oxidoreductase, Lactate dehydrogenase, LDH)?
Lactate dehydrogenase (LDH) is an enzyme involved in energy production and is found in almost all cells in the body. The largest amount of LDH is found in the cells of the heart, liver, muscles, kidneys, lungs and blood cells.
Normally, serum LDH levels are low. When cells are damaged and / or destroyed, the level of LDH increases, which is reflected in the results of this test. However, an increase in the level of LDH is not specific, that is, it is impossible to establish the exact localization of the lesion based on this indicator alone.
Why determine the level of ALT in the blood?
LDH can be used to track the dynamics of severe conditions, for example, hemolytic anemia, muscular dystrophy or severe infections – a decrease in the indicator over time signals the effectiveness of the prescribed therapy.
Periodic measurement of LDH is necessary to monitor some types of treatment, for example, chemotherapy for malignant tumors, when a decreasing level of this indicator indicates the effectiveness of therapy.
In what diseases does the level of ALT in the blood rise?
LDH increases with myocardial infarction, stroke, hemolysis (destruction of red blood cells), infectious diseases (infectious mononucleosis, meningitis, encephalitis, etc.)), sepsis (an extremely serious condition when an infectious process leads to disruption of the work of many organs – multiple organ failure), acute damage to the liver, kidneys, muscle injury, bone fractures, various types of cancer, pancreatitis (inflammatory lesion of the pancreas), etc. …
Thus, for an accurate diagnosis of a specific disease, a doctor who finds an increase in LDH is likely to prescribe an additional examination in accordance with complaints, medical history and examination data.For example, if there is a suspicion of liver damage and an established increase in the LDH level, additional studies will be indicators of ALT, AST, in some cases – alkaline phosphatase (ALP). If myocardial infarction is suspected, it is advisable to investigate the levels of cardiospecific enzymes, such as troponin, myoglobin, creatine kinase (CPK).
Why can the analysis result be incorrect?
If all the recommendations were followed in preparation for the study, then its result will be correct.However, there are situations when a person cannot refuse to take certain drugs, and these drugs can distort the result. For example, products containing acetylsalicylic acid and some anti-inflammatory drugs can increase serum lactate dehydrogenase levels. You need to consult a doctor about taking them and, if possible, cancel them 2-3 days before the test.
Rules for preparation for blood tests to determine the LDH level
It is preferable to take blood in the morning on an empty stomach, after 8-14 hours of the night fasting period (you can drink water), it is permissible in the afternoon after 4 hours after a light meal.On the eve of the study, it is necessary to exclude increased psycho-emotional and physical activity (sports training), alcohol intake.
Interpretation of test results contains information for the treating physician and does not constitute a diagnosis. The information in this section cannot be used for self-diagnosis and self-medication.An accurate diagnosis is made by a doctor using both the results of this examination and the necessary information from other sources: anamnesis, results of other examinations, etc.
Interpretation of LDH blood test results
Units of measurement : U / l.
LDH level, U / l
up to 1 year
from 1 to 3 years
from 3 to 6 years old
from 6 to 12 years old
from 12 to 17 years old
more than 17 years
- Liver pathology (viral and toxic hepatitis, obstructive jaundice, liver cirrhosis).
- Myocardial infarction and pulmonary infarction.
- Diseases of the blood system (hemolytic, pernicious, megaloblastic and sickle cell anemia, acute leukemia).
- Malignant neoplasms of various organs.
- Diseases of skeletal muscles (trauma, atrophy).
- Kidney pathology (glomerulonephritis, pyelonephritis, kidney infarction, etc.).
- Any pathological processes that are accompanied by cell destruction and loss of cytoplasm (traumatic shock, hemolysis, extensive burns, hypoxia, extreme hypothermia, etc.)etc.).
- Acute pancreatitis.
- Alcohol and certain medications (eg caffeine, anesthetics, cephalosporins, nonsteroidal anti-inflammatory drugs, sulfonamides).
What can the tests say about the heart?
What are analyzes? Analyzes are confirmation or exclusion of a particular disease, which was an opinion after a clinical examination of a patient. With their help, the doctor will find out what exactly prevents your body from living and working normally, what is the state of its individual organs and systems.
So, what do these analyzes say if there are pains in the region of the heart? Determination of enzymes contained within cells is of great importance in the diagnosis of diseases associated with myocardial damage. And depending on which and how many cells die, their values will also change.
Indicators of biochemical blood test:
ALT (alanine aminotransferase): to 68E / L, when assessing the level of this enzyme, it should be borne in mind that it is contained not only in the myocardium, but to a greater extent in the liver, therefore AST and ALT are always determined together, which helps in differentiating damage to the heart and liver.The timing of the increase in ALT is similar to AST.
AST (aspartate aminotransferase) : up to 45E / L, this enzyme is found in large quantities in the myocardium, and its increase, in most cases, indicates damage to cardiomyocytes – muscle cells of the heart; an increase in AST in the blood serum is observed in myocardial infarction (95-98%) cases within 6-12 hours from the onset of the disease. The maximum increase is noted on days 2-4, and on days 5-7, the enzyme level returns to normal.There is a clear relationship between the AST numbers and the size of the heart muscle necrosis focus. Therefore, if the amount of necrosis is less than 5 mm in diameter, it is possible to maintain the level of this enzyme within the normal range, which must also be taken into account.
LDH (lactate dehydrogenase) and the fraction constituting this indicator: up to 250 U / L, is considered a specific marker in AMI, an increase in the activity of the isoenzyme LDH1 and LDH2, even with normal indicators of total LDH activity, indicates the presence of small necrosis in the heart muscle.With AMI, its level rises rapidly by 2-4 days, and returns to normal only at 2-3 weeks. The LDH level provides valuable information about MI throughout the course of the disease. Other fractions LDH3 and LDH4 are enzymes of the lung tissue, LDH5 – liver.
CPK (creatine phosphokinase) and the fractions that make up this enzyme: up to 190 U / L, creatine phosphokinase – is considered a specific marker (especially an increase of more than 10 times) in acute myocardial infarction. It increases in the acute period (in the first 4-8 hours from the onset of the disease), much ahead of the activity of the above enzymes and is a marker of early diagnosis of AMI, especially the CPK-MB isoenzyme.After 8-14 hours, the CPK value can reach its maximum value, and normalization can occur in 3-4 days. Also, the value of CPK may increase with myocarditis;
troponin test: to 0.4 μg / l. Troponin is a specific contractile protein that is part of the structure of the heart muscle and skeletal muscles. This test is a diagnostic marker for suspected acute myocardial cell damage, is one of the key results in the diagnosis of acute myocardial infarction;
myoglobin: 12-92 μg / l.A muscle tissue protein that is involved in cell respiration. If it appears in the blood, it is regarded as a decay product of the muscle tissue of the heart or skeleton, with the appropriate clinic, it may indicate necrosis (necrosis) of the focus of the muscle tissue of the heart, therefore it is also considered a specific marker of this pathology.
Indicators of ALT, AST, CPK, CPK-MB, LDH, myoglobin and troponin test closely correlate with the size of the necrosis focus in the heart muscle, and therefore have not only diagnostic, but also prognostic value.
Acid phosphatase: 67-167 nmol / (s · L), increases in activity in patients with severe, complicated MI, mainly transmural;
C-reactive protein (CRP): up to 0.5 mg / l, its detection indicates the presence of a pathological process in the body, in particular inflammatory or necrotic. It belongs to the proteins of the so-called “acute phase”. A strongly positive reaction to CRP indicates the severity of the inflammatory process.
sialic acids: 2.0-2.36 mmol / l, the content of sialic acids may increase with endocarditis, MI;
electrolytes , mainly represented by ions K + (norm 3.6 – 5.2 mmol / l), Na + (norm 135 – 145 mmol / l), Cl- (norm 100 – 106 mmol / l), Ca2 + ( norm 2.15-2.5 mmol / l). An increased amount of potassium in the serum may be accompanied by a clinically disturbed heart rhythm, which is confirmed by an ECG. Atrioventricular blockade of the cardiac conduction system may develop, a syndrome of premature excitation of the ventricles, ventricular fibrillation, and such a formidable violation as cardiac arrest may develop.Therefore, patients with cardiac arrhythmias need to control the content of K + ions in the body. On the other hand, a decrease in potassium in the blood can also lead to adverse consequences in these patients – myocardial hyporeflexia. A decrease in the level of sodium ions can be accompanied by the development of insufficiency of the cardiovascular system, since the ratio of K + and Na + ions, as regulators of processes in the cell, is in constant interaction and a decrease in one leads to an increase in the other ion.Hyperchloremia occurs in patients with kidney disease and can also lead to the development of cardiovascular failure;
lipid spectrum, is associated in a common person with the word “cholesterol”. In this case, substances (lipoproteins of various densities, triglycerides) are determined that are involved in the exchange of cholesterol (CS) (the norm in the blood is 3.1 – 5.2 mmol / l). In addition to the value of total cholesterol, an important indicator is the atherogenic coefficient (the norm is up to 4), which shows the ratio of “good” and bad “lipids involved in the metabolism of fats and cholesterol, and the threat of the development or progression of atherosclerosis and all the ensuing consequences.An increase in lipoprotein and triglyceride fractions can be both a physiological state (alimentary in nature) and a pathological state. An increase in lipids is characteristic of widespread atherosclerosis, obesity accompanying and causing arterial hypertension. Or it would be more accurate to say that this is a disruption in the functioning of internal organs and intermediate links of lipid and triglyceride metabolism, expressed in an increase in the atherogenic index, causes the deposition of cholesterol in vessels of various diameters, the deposition of “reserve fat”, which leads to the above diseases.Therefore, with widespread atherosclerosis, in this blood test, you can see increased values of ß-lipoproteins and total cholesterol. However, a decrease in the concentration of phospholipids can be seen. But even so, it is necessary to take into account that there are age-related fluctuations in blood fats.
coagulogram – an analysis by which you can see the “viscosity” of the blood, or in other words, whether there is a threat of blood clots, which can lead to the formation of blood clots with different localization, which in turn can be complicated by pulmonary embolism, in which there is instantaneous death.Or, on the contrary, to see how high the likelihood of bleeding is and whether it will be able to stop on its own, after an operation, for example, to replace a heart valve.
Any analysis or research gives the doctor additional information that helps to more accurately diagnose, determine the stage of the disease, and prescribe treatment. Analyzes also help to control the course of the disease, the effectiveness of the prescribed treatment, as well as ensure the safety of therapy. But sometimes additional research is required to confirm or complement the results of past analyzes.
Fedorova Lyubov Alekseevna – doctor of the first category, therapist, cardiologist of the Tet-a-Tet Medical Center.
Indirect markers: C-D-T.RU
Laboratory markers of alcohol consumption are divided into groups of direct and indirect biomarkers. Biomarkers differ in the mechanisms of their pathological increase, which largely determine their analytical specificity; the dose of alcohol and the duration of its use required to increase the concentration of the biomarker; half-life (or metabolic period) in the human body, and this indicator is extremely important in assessing the diagnostic significance of the marker in relation to the differentiation of chronic abuse and the possibility of early detection of relapse.
The group of indirect markers includes a wide range of indicators, the analytical characteristics and diagnostic significance of which can vary within wide limits.
1. Average erythrocyte volume ( MCV )
Mean Red Blood Cell Volume (MCV) is an index of red blood cell size and is calculated as the ratio of hematocrit to red blood cell count. The mechanism by which alcohol causes an increase in MCV is the direct toxic effect of alcohol on red blood cells.Folic acid and vitamin B12 deficiencies secondary to alcohol consumption and liver damage can also cause an increase in MCV. Increases in MCV have been observed in chronic abuse and correlate with both the amount consumed and the frequency of use. However, the change in MCV in response to a change in the level of alcohol consumption is very slow: an increase in MCV can occur only after 1 month of consuming more than 60 g of alcohol per day; it may take several months of abstinence to normalize MCV.MCV is not an informative marker for monitoring acute alcohol consumption, relapses or binges due to the slow response of the indicator to changes in the amount of alcohol entering the body, which is due to the long half-life of erythrocytes (erythrocyte life cycle is 100-120 days). MCV may increase nonspecifically in individuals with hypothyroidism, reticulocytosis, and smokers. Low specificity of the marker is observed when testing elderly patients.MCV can be lowered in people with iron deficiency (alimentary anemia, bleeding of various origins), with thalassemias and a number of chronic diseases (for example, with chronic gastrointestinal diseases). Thus, the main disadvantage of the MCV marker is its low sensitivity (40-50%) and insufficient specificity in both inpatients and outpatients.
2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
An increase in the level of aspartate aminotransferase is often the first detectable indicator of the response of hepatocytes to the effects of drugs and toxic agents.The level of AST and ALT reflects generalized damage to liver cells or an increase in the permeability of cell membranes, both alcoholic and non-alcoholic genesis. Both enzymes enter the bloodstream when cell membranes are damaged and are present in many tissues, while most tissues contain less AST than ALT; the only exception is liver tissue, where both enzymes are present in approximately equal concentrations. AST and ALT levels (half-lives of 17 and 47 hours, respectively) increase in the case of alcohol abuse, but due to extremely low sensitivity and specificity, these markers cannot be considered as independent indicators of chronic abuse.
3. Gammaglutamyltransferase (GGT)
Gammaglutamyltransferrase (GGT) is a membrane glycoprotein (enzyme) that catalyzes the transfer of the gammaglutamyl residue of glutathione to various protein acceptors. The elevation of serum GGT in response to varying amounts of alcohol and for different durations of abuse can vary significantly from patient to patient. First of all, GGT is an indicator of chronic use of high doses of alcohol, but it remains within the normal range in drunken alcoholics and in those who drink but do not abuse, if they do not have concomitant liver diseases.The half-life of GGT (the time it takes for the enzyme to halve its initial activity) is 14 to 26 days, and the serum concentration of the enzyme usually returns to normal 4-5 weeks after stopping alcohol.
The sensitivity of GGT in persons with a high alcohol load (from 40 to 540 g of alcohol per day), according to a number of studies conducted in Finland, is 58%. Individuals who consume critically high amounts of ethanol, but are not classified as addicts, have significantly lower GGT sensitivity (20-50%), especially when diagnosed in primary health care facilities.A physiological increase in the level of GGT is observed in people over 65 years old, regardless of the amount of alcohol they drink, and, on the contrary, in people under 30 years old, the physiological level of GGT can be lowered.
In a large-scale study of the Finnish population (3974 men and 2988 women), it was shown that GGT has a low sensitivity and low diagnostic value in differentiating persons with a high alcohol load (over 280 g per week) from those with an average (105-280 g in week) and low (105 g per week) load.
GGT can increase nonspecifically in diseases of the pancreas, type II diabetes, obesity, hypertension, myocardial infarction, chronic obstructive pulmonary disease and renal failure. A more pronounced GGT response is seen in chronically abusive men from South Asia, Brazil, Mexico, and Africa.
Thus, the main disadvantage of this biomarker is its low specificity. A number of drugs and pathological conditions can increase GGT, leading to false positive diagnostic results.Despite the drawbacks, the measurement of the GGT level when used in combination with other, more specific markers, such as, for example, carbohydrate-deficient transferrin, can give good, diagnostically significant results.
In general, the traditional indirect markers of alcohol consumption described above can be characterized as inexpensive, easy to implement, but insufficiently reliable indicators with a number of significant limitations:
a) these indicators do not reflect alcohol abuse itself, but liver dysfunctions associated with abuse.Thus, these tests have a rather low diagnostic specificity, since they give false-positive results in a number of liver diseases not associated with alcoholism, as well as when taking certain medications;
b) in addition, some of these tests are not sensitive enough to detect the fact of alcohol abuse before the onset of organic liver damage;
c) the specificity and sensitivity of these markers vary widely depending on gender, age, concomitant pathology, not meeting the criteria of the “ideal marker”.
4. Carbohydrate-deficient transferrin (CDT)
In recent years, a new marker, carbohydrate-deficient transferrin (CDT), has been increasingly used in world practice. According to literature data, including published results of large multicenter, clinical and validation trials, CDT has the best analytical performance of the existing laboratory assessment markers for chronic abuse. A specific increase in CDT is observed in persons consuming at least 50-80 g of alcohol for at least 7-10 days, which allows establishing the fact of chronic abuse in the laboratory.
At the same time, in the majority of patients with liver diseases, the CDT level remains within the normal range, which compares favorably with the indicators of GGT, ALT and AST. Certain chronic liver diseases (primary biliary cirrhosis, highly active chronic hepatitis, severe decompensated cirrhosis) can cause false positive results. Nevertheless, according to the data of various studies, this marker demonstrates the highest indicators of specificity and sensitivity (Table 1).
Table 1. Comparative characteristics of the marker CDT *
Characteristics of the indicator
Time required to normalize the indicator after cessation of use
Threshold for alcohol consumption causing a positive result
50-80 g per day
80-200 g per day
<80 g / day
|Period of regular alcohol consumption resulting in a positive result||
* The variability of the indicators is explained by the difference in the analytical characteristics of the methods for assessing markers, the characteristics and size of the sample of research participants, etc.
World Health Organization in the study “Comparative Quantification of Health Risks” (“Comparative study of risk factors”) from 2004 identifies 4 categories of people, depending on the amount of alcohol consumed.
Daily consumption of absolute alcohol, g
0 during the last year
Average alcohol consumption, category I
0 – 39.99
Average alcohol consumption, category II
Average alcohol consumption, category III
Alcohol consumption by men and women daily in amounts exceeding 100 g and 60 g, respectively, is a very high risk of developing alcohol-associated diseases.
The CDT marker allows you to identify individuals with an average (and higher) risk of such diseases.
In 2005, the CDT marker was approved by the Food and Drug Administration (FDA) as an indicator of chronic abuse, and is now widely used in Western Europe and the United States.
How does liver health affect performance – Society
Have you noticed weakness, drowsiness, irritability, decreased attention and low mood? These symptoms are often attributed to a sleepless night, the result of a busy day, or vitamin deficiency.And, as a rule, you don’t pay attention to them until some trouble happens. Then there is a reason to think about what is really going on.
One of the probable causes is an increase in ammonia in the blood. This happens due to a violation of the liver, which ceases to cope with cleansing the body of toxins. Let’s figure out where this molecule known from school comes from in the body and how its presence affects the performance and well-being of a person.
What’s going on?
Ammonia is formed in our body in the course of life and is a toxin, its excess is removed by the liver. If something is wrong with the liver, the main filter of the body, detoxification processes are disturbed and the level of toxic ammonia in the blood increases, ammonia reaches the brain and inhibits its work. Ammonia is dangerous for the liver itself, as it can aggravate its condition.
As strange as it may sound, we ourselves may be to blame for the fact that a large amount of ammonia accumulates in our body.The protein diet, which is so loved by lovers of a healthy lifestyle and athletes who want to build muscle or get rid of excess fat, is often one of the reasons. This also includes the regular use of alcohol, fatty foods, as well as active physical activity and systematic intake of medications. All this creates an additional and sometimes excessive stress on the liver, which reduces its ability to cleanse it of toxins.
Fans of a sports lifestyle should remember that increased ammonia reduces endurance during sports training, slows down the recovery process between classes.Stiffness and pain in muscles after jogging or playing, feeling tired are also partly his fault.
The toxin inhibits the functions of the brain, which negatively affects concentration and reaction speed. This should be paid attention to employees of large enterprises, financiers, managers and other office workers, whose performance may fall.
Increased ammonia in the body poses a great danger to motorists. Several years ago, in the course of an independent Smart Radar study, which involved 42 drivers aged 20 to 45 with at least three years of experience, Russian scientists proved the relationship between an increase in the frequency of traffic violations and the presence of liver diseases.It turned out that all participants in the study with the initial stages of liver disease had an increased level of ammonia in the blood, which negatively affected concentration and led to traffic violations and accidents.
How to protect the liver?
In order not to accumulate ammonia in the body, do not overload the liver – to abuse fatty foods, alcohol and protein supplements when playing sports. Simple rules to follow to make your liver healthy. If problems have already arisen, then you can use a proven remedy – the German hepatoprotector-detoxifier “Hepa-Merz”.It contains the active substance L-ornithine-L-aspartate, which decomposes into natural amino acids ornithine and aspartate 20-25 minutes after ingestion and begins to solve the problem.
The drug reduces the increased level of ammonia in the body, improves liver performance and test parameters, restores metabolism. The standard course “Hepa-Merz” lasts one month, but the manufacturer promises the first results in 10 days. “Hepa-Merz” is the winner of the Russian Pharma Awards in the category “A drug that has a positive effect on liver function”.
How do you know when it’s time to check your liver health?
Liver diseases are difficult to detect in the early stages, so the presence of symptoms characteristic of an increased level of ammonia in the body may be a reason to see a doctor. Another way to find out about the problem is to take a test, which in just 40 seconds will help you know if you should be worried. For the result to be accurate, it is better to be tested several times, in the morning, at intervals of a couple of days.
If the test fails several times in the allotted time, you should consult a doctor and make an analysis to determine the activity of the liver enzymes ALT, AST, GGTP.And for prevention, experts recommend taking biochemical blood tests and doing an ultrasound of the liver at least once a year. This is especially important for people whose work requires maximum concentration.
CONTRAINDICATIONS ARE AVAILABLE. NEEDS CONSULTATION WITH A SPECIALIST
Laboratory diagnostics of myocardial infarction in St. Petersburg, price in SZTSDM
Myocardial infarction is an acute form of coronary heart disease.The essence of the pathology is a sharp disruption of the blood supply to the tissues of the heart and the occurrence of a site of necrosis. Modern techniques make it possible to respond in a timely manner to the disease; there are endovascular and medication methods for restoring blood flow. The question of timely diagnosis remains open – after all, the beginning of effective therapeutic measures depends on this. In order to determine the presence of a heart attack, a number of techniques are used, including an assessment of the clinical picture, instrumental and laboratory methods.
Clinical picture of pathology
Heart attack symptoms can be varied. The first and main symptom is pressing pain behind the sternum, which has a compressive character, often the patient notes that it is burning and very intense. Pain occurs at the height of emotional stress or physical exertion. Its sudden occurrence leads to general weakness, interruptions in breathing.
In addition to pain, the following symptoms may be observed:
The pain, as a rule, is localized behind the sternum, but can radiate to the left arm, shoulder, interscapular region, jaw, upper abdomen.It depends on the location of the necrosis.
There are clinical forms of heart attack:
The patient has a dry cough, shortness of breath, chest pain.
The pain is located in the upper abdomen, and there is severe nausea.
There is a failure of the heart rhythm, weakness, short-term loss of consciousness.
The patient complains of severe headache.
There are asymptomatic forms of heart attack, they are observed in diabetes mellitus, as well as in patients who abuse alcohol. In this case, general weakness and impaired consciousness may be observed, but there is no typical pain that is characteristic of a heart attack.
Modern diagnostic methods
If there is a suspicion of a heart attack, there is anamnestic data about coronary heart disease and characteristic clinical signs, the doctor prescribes a diagnostic program.It consists of the following methods:
Let’s take a closer look at these research methods.
An electrocardiogram is a graphical representation of the conduction of an impulse through the fibers of the myocardium. If, due to necrosis, conductivity is disturbed, this will be displayed on the record. According to the changes on the ECG, the localization of the necrosis zone can be distinguished. Also, on the graph you can see the phase of the heart attack – acute or subacute.
Complete blood count
In the general analysis of blood, no specific changes are observed and therefore, on its basis, a diagnosis cannot be made.With a heart attack, leukocytosis develops, which occurs a few hours after the start of the process and reaches a maximum by the end of the day. The increased indicator is kept for several days and gradually returns to normal. Leukocytes do not increase strongly, as, for example, in infectious pathology, which allows differential diagnosis. This is important in an atypical clinical picture of myocardial infarction, when the doctor may suspect several pathologies. In a general blood test, you can also see an increased ESR, which remains so for several weeks.Eosinophils also increase, they remain elevated for about a week.
Biochemical blood test
Alanine aminotransferase (ALT)
Indicator of destruction of hepatocytes and cardiomyocytes. It increases with hepatitis of various etiology, heart attack, toxic lesions of internal organs. ALT is an active component of liver metabolism, an enzyme that speeds up the metabolism of amino acids. The highest concentration of the substance is found in the cells of the liver, kidneys, heart, as well as in skeletal muscle tissue.Since its localization is the cytoplasm, it enters the blood when the cell membrane is destroyed. The more massive the site of destruction, the higher the concentration of the enzyme in the blood. The peak of enzyme activity during a heart attack is 12 hours.
An increase or normalization of the ALT level is a marker of the state of patients of various profiles with diseases of internal organs and soft tissues. Depending on the disease, ALT can increase moderately or sharply, for example, the highest concentration is observed in hepatitis.
With a heart attack, the de Ritis coefficient is used, which consists of comparing the activity of AST and ALT. If the indicator exceeds the norm, this indicates a heart attack, and if it is below its value, it is possible that necrosis of the renal tissue or the active phase of hepatitis has developed. Naturally, no diagnosis is made on the basis of ALT. For this, more specific markers are used. The level of transaminases is checked in a general biochemical analysis for differential diagnosis and control of the general condition of the patient.
Aspartate aminotransferase (AST)
Marker of the state of the tissues of the heart, liver. It increases with viral hepatitis, toxic damage to the tissues of the heart and hepatocytes. It is also used for preventive examination, if necessary, to confirm or exclude a heart attack. This substance is responsible for the exchange of amino acids in cells, therefore, its greatest amount is found in the cells of the liver, heart, skeletal muscles and erythrocytes. If the cells of these organs are damaged, transaminase is released into the blood, where its increase can be detected.There is a permissible level of the enzyme in the blood, because the cells of the organs are periodically destroyed, but in pathological conditions this indicator increases several times and tens of times. The peak of the maximum concentration in the blood is 12 hours after the onset of a heart attack. A comparison of ALt and AST indicators is also used. Each of these enzymes increases in certain pathologies, and in the event of a heart attack, their ratio is assessed. AST is not a specific indicator for a heart attack; it complements the general picture of a laboratory study.
Creatine kinase MB
This substance is an isoenzyme, a marker of the state of the heart muscle. Takes part in the metabolism of creatine and creatine phosphate. This substance is contained only in the myocardium, therefore it increases with its diseases – myocarditis, heart attack, rhabdomyolysis, pericarditis. The level of the substance is a marker in the acute and subacute phase of the process. A short-term increase in the indicator is observed during surgical interventions on the heart, which reflects the response of the myocardium to treatment.The maximum concentration during a heart attack is observed 12 hours after the onset. High activity indicates a significant size of the affected area. The increase in this fraction of CPK is compared with the general indicator of the substance in the body. In principle, the assessment of the level of CPK MV is used for early diagnosis of myocardial damage, as well as for differentiation of the condition from other diseases. An increase in the marker can speak, in addition to a heart attack, about conditions such as shock, poisoning and intoxication, infectious lesions of the heart tissue.
A protein that is found in high amounts in skeletal muscle and myocardium. There are varieties of this protein that are responsible for different phases of muscle contraction. All these proteins are cardiospecific and indicate the state of the myocardium. Damage to the myocytes of the heart leads to the release of the substance into the blood, where it can be detected using laboratory tests. The area of necrosis affects the level of increased troponin levels in the blood.Troponin I is the most sensitive and specific for infarction. Increased troponin is retained for 5-6 days after the onset of the pathological process.
It is a protein found in muscle cells and contains iron molecules. It is similar in structure to hemoglobin – an iron-containing blood protein. The function of myoglobin is also similar – it transports oxygen to myocytes, muscle cells. With necrosis, the destruction of muscle cells occurs, myoglobin is released and enters the bloodstream, where it can be found.Protein from the blood is excreted along with the kidneys. It can be determined in the blood within a few hours after the onset of the pathological process, within 2-3 days it can still be determined. This marker is one of the first to react, which increases its diagnostic value. With necrotic changes, it increases 7-10 times, depending on the area of the necrosis area. For comparison, the period of peak increase in the remaining markers is 12 hours, while for myoglobin it is 6 hours. The analysis is normalized just as quickly.They can remain elevated for longer than a day if complications occur, for example, an expansion of the area of necrosis. Sometimes new foci occur, then myoglobin rises again, which requires dynamic control of the indicator. The negative result of the study is also important, which, in comparison with the clinical picture, makes it possible to exclude pathology. In addition to a heart attack, myoglobin can talk about a syndrome of prolonged compression. muscle pathology, inflammatory processes.
What can influence the result?
The test results are affected by the time of the diagnosis that has passed since the onset of the disease.Also, the changes depend on the prevalence of the necrosis zone, the localization of the process. Many laboratory parameters that are observed during a heart attack can accompany other pathological conditions. For example, transaminases increase in diseases of internal organs, impaired liver function, hepatitis of various etiologies, against the background of alcohol consumption. Troponin increases during inflammatory processes in the myocardium. Creatine kinase and myoglobin can fluctuate in violation of the structure of muscle tissue, rhabdomyolysis, various inflammatory processes, myositis.Many of these indicators remain elevated after surgery, which should be taken into account when taking a patient’s anamnesis.
If possible, it is advisable to take the analysis on an empty stomach; before donating blood from a vein, you should rest a little. It is good if before the study it is possible to exclude the use of alcohol, nicotine and physical activity. It is necessary to tell the doctor which drugs were taken, as they can also affect the test results.
Timely diagnosis of a heart attack allows you to start treatment on time. In the case of a heart attack, this is especially important, since the clock sometimes goes by the clock. Effective therapy or surgery can prolong a patient’s life, improve quality, and reduce the risk of complications. You need to trust your health to trusted medical institutions, where there are conditions for accurate diagnosis in a short time.
90,000 ASAT – what is it? Properties and indications
No. of analysis in the “Science” database: 123.
Aspartate aminotransferase (AST, AST) is an endogenous enzyme belonging to the class of transferases, a subclass of aminotransferases (transaminases). Aspartate aminotransferase is synthesized intracellularly, and normally only a small part of this enzyme enters the bloodstream. Determination of AST activity in blood serum is a diagnostic indicator of damage, primarily, of myocardial and liver tissue.
AST, AST, glutamate oxaloacetate transaminase, aspartate aminotransferase, EC 184.108.40.206.
UV kinetic test.
In what units is AST activity expressed
U / L (unit per liter).
Biomaterial for analysis
Preparation for research:
Blood sampling should be done in the morning on an empty stomach. After the last meal, at least 12 hours should pass. Physical and emotional stress should be avoided 30 minutes before blood sampling. Do not smoke for 30 minutes before donating blood.
AST catalyzes the transamination reaction, which results in the conversion of oxaloacetate (oxaloacetic acid, PAA) to aspartic acid (aspartate) by transferring the amino group to the PAA molecule. The second product of the reaction is α-ketoglutaric acid (α-ketoglutarate), one of the intermediate products of the tricarboxylic acid cycle. The reaction plays an important role in the release of ammonia from amino acids. The ammonia is then processed in the urea cycle, i.e.As the aspartate obtained during the reaction is needed for the formation of argininosuccinate. In addition, the reverse reaction converts aspartate to oxaloacetate. Thus, this reaction is of great importance in the processes of gluconeogenesis.
For diagnostic purposes, the determination of AST activity is usually carried out in conjunction with the determination of the activity of another aminotransferase – alanine aminotransferase (ALT, ALT). Both enzymes are present in cells of various tissues, but ALT is present in significant amounts only in liver tissue.In myocardial tissue and skeletal muscles, the amount of AST is 20 times higher than the level of ALT. Sometimes there is a very high activity of AST, which can exceed the normal limit by 100 times. This occurs in diseases associated with severe tissue damage – acute hepatitis, compression syndrome, tissue hypoxia. With hepatitis, AST readings exceed the norm by 10–20 times and this happens during the prodromal stage (at the time of the onset of jaundice or shortly before that). With myocardial infarction, AST activity increases after 12 hours.The peak of activity falls on 24-36 hours after a heart attack with an excess of the norm by 10 times. Then the indicators decrease within two to three days, which is evidence of the absence of damage to the heart muscle.
In most diseases associated with an increase in the concentration of AST, there is a simultaneous, albeit less high, rise in the concentration of ALT. However, in hepatitis, the plasma ALT activity may exceed the AST activity. AST concentration is often measured as an element of the “biochemical profile”.AST concentrations exceeding the upper limit of the norm by more than 20 times are most often observed in the prodromal stage of viral hepatitis. Double increases in concentration are sometimes observed in the absence of clinical symptoms of tissue damage. The reason in this case is most often alcohol abuse. This enzyme lacks tissue-specific isoforms, and if no other biochemical abnormalities and no obvious reasons for such an increase are found, then the analysis should be repeated after 2-3 weeks.
What the analysis is used for
For determination of AST activity in blood serum.
- myocardial infarction,
- liver cancer.
Reference values (norm)
The normal level of AST activity in the serum of an adult is:
- for men 0-50 U / L,
- for women 0–45 U / l.
Exceeding the upper limit of the norm by more than 10 times:
- acute hepatitis and liver necrosis,
- severe constriction syndrome,
- severe tissue hypoxia (the value of AST activity can sometimes exceed the upper limit of the norm by more than 100 times).
Exceeding the upper limit of the norm by 5-10 times:
- myocardial infarction,
- after surgery or trauma,
- skeletal muscle disease,
- chronic hepatitis.
Exceeding the upper limit of the norm by less than 10 times:
- physiological (in newborns),
- other liver diseases,
- hemolysis (in vivo and in vitro).
Decrease in AST activity has no clinical significance.
Vitamin B12 (cyanocobalamin, cobalamin, Cobalamin)
Method of determination
Microparticle chemiluminescence immunoassay, Architect i2000 (Abbott).
Vitamin necessary for normal blood formation (formation and maturation of erythrocytes).
Vitamin B12 contains cobalt and a cyano group that form a coordination complex. It is not synthesized in the human body.
Sources of vitamin are intestinal microflora, as well as animal products (yeast, milk, meat, liver, kidneys, fish and egg yolk). Human milk contains vitamin B12 in the form of methylcobalamin, the main form in which the vitamin is found in the human body.During digestion in the stomach, cyanocobalamin binds to Castle’s intrinsic factor, a protein synthesized by the parietal cells of the gastric mucosa, which also produce hydrochloric acid. In the ileum, this complex is absorbed; in the cells of the mucous membrane, vitamin B12 is released and binds to a protein – transcobalamin, which delivers cyanocobalamin to the liver and other tissues.
The main place of vitamin B12 deposition is the liver. A large amount of it is absorbed by the spleen and kidneys, slightly less – by the muscles.The total reserves of cobalamin in the body of an adult are about 2 – 5 mg. Vitamin metabolism is very slow. It is excreted by bile, in the intestine, the main part of it is reabsorbed, that is, it is characterized by enterohepatic circulation.
It takes a long time for the development of vitamin deficiency with a reduced intake of it in the body: about 5 – 6 years. Vitamin B12 plays an important role in metabolic processes; as part of cobalamin enzymes, it participates in protein, fat and carbohydrate metabolism.
Vitamin B12 has two coenzyme forms: methylcobalamin and deoxyadenosylcobalamin (cobamamide). The main function of active forms of coenzymes is the transfer of methyl one-carbon groups (transmethylation). Participate in the exchange of proteins and nucleic acids (synthesis of methionine, acetate, deoxyribonucleotides).
Cyanocobalamin is a coenzyme that plays an important role in the metabolism of folic acid, in particular, participates in its transport to cells. With the participation of methylcobalamin, an active form of folic acid is synthesized in the body, which takes part in the formation of pyrimidine and purine bases, nucleic acids.
With a lack of cobalamin, the most pronounced changes develop in proliferating cells, for example, in the cells of the bone marrow, oral cavity, tongue and gastrointestinal tract, which leads to disruption of hematopoiesis, glossitis, stomatitis and intestinal malabsorption. Vitamin B12 contributes to the accumulation of sulfhydryl groups in erythrocytes, mainly glutathione, therefore its deficiency leads to impaired division and maturation of erythrocytes and the development of megaloblastic anemia. Vitamin B12 is a cofactor for the enzyme homocysteine methyltransferase, which is involved in the conversion of homocysteine to methionine.Methionine is important for the synthesis of phospholipids and the myelin sheath of neurons, therefore, vitamin B12 deficiency is accompanied by neurological symptoms (mental disorders, polyneuritis, funicular myelosis – spinal cord damage).
Neurological symptoms of vitamin B12 deficiency are different depending on the severity of the pathology. Early signs include dysfunction of the posterior horns of the spinal cord with gait disturbance. Later, they develop a lesion of the pyramidal, spinocerebellar and spinothalamic tracts, accompanied by muscle weakness, progressive spasticity, hyperreflexia, and a scissor gait.With prolonged vitamin B12 deficiency, dementia and neuropsychiatric disease occur.
Cyanocobalamin, participating in the synthesis of choline and methionine, has a beneficial effect on the liver, prevents the development of fatty hepatosis. Adenosylcobalamin serves as a coenzyme of methylmalonyl-CoA mutase, an enzyme that converts methylmalonic acid to succinic acid. Significant inhibition of this reaction leads to the development of a life-threatening condition – methylmalonic aciduria. Clinically, this condition is manifested by a significant child’s lag in weight, reduced protein tolerance, ketoacidosis, hypoglycemia, hyperammonemia and hyperglycemia, a high content of methylmalonic acid in the urine.