Category Archives: symptoms – aggravation and help

Jaundice

WHAT IS JAUNDICE?

The word “jaundice” comes from the French word jaune, which means yellow.

Jaundice is a yellowish staining of the skin, sclera (the white of the eyes), and mucous membranes by bilirubin, a yellow-orange bile pigment. Bilirubin comes mainly from the breakdown of red blood cells, and is basically a waste product that’s then disposed of by your liver.

Jaundice usually appears when the bilirubin in your blood is more than 3 mg per dL (51.3 µmol per L). The classic definition of jaundice is a serum bilirubin level greater than 2.5 to 3 mg per dL (42.8 to 51.3 µmol per L) as well as having yellow skin and eyes.

Your body processes bilirubin in 3 phases: prehepatic (before it gets to the liver), intrahepatic(whilst in the liver), and posthepatic(after leaving the liver). If any of these aren’t working properly you can become jaundiced.

PREHEPATIC

The human body produces about 4 mg per kg of bilirubin per day, from the breakdown of blood cells. Bilirubin is then transported from to the liver for conjugation (where it needs to link up with other enzymes and chemicals so that it can be removed from the body) .

INTRAHEPATIC

Unconjugated bilirubin is insoluble in water but soluble in fats. Therefore, it can easily cross the blood-brain barrier or enter the placenta. The unconjugated bilirubin is conjugated with a sugar via the enzyme glucuronosyltransferase (the enzyme that people with GS don’t have enough of) and is then soluble in the bile.

POSTHEPATIC

Once soluble in bile, bilirubin is transported through to the gallbladder, where it is stored, or passed on to the duodenam. Inside the intestines, some bilirubin is excreted in the stool, while the rest is dealt with by the bacteria in your gut.

JAUNDICE AND OTHER SYMPTOMS

Some people with jaundice have no symptoms at all.  But some may have an acute illness, which is frequently caused by infection, may seek medical care because of fever, chills, abdominal pain, and flu-like symptoms. For these patients, the change in skin color may not be their greatest concern!

Patients with noninfectious jaundice may complain of weight loss or itching / skin discomfort. Abdominal pain is the most common symptom in patients with pancreatic or biliary tract cancers.Even something as nonspecific as depression may be a symptom in patients with chronic infectious hepatitis and in those with a history of alcoholism.

‘False’ jaundice can happen if you eat foods rich in beta-carotene (e.g., squash, melons, and carrots). Unlike true jaundice, you don’t get yellow eyes, or changes in bilirubin level.

CAUSES OF JAUNDICE:

PREHEPATIC CAUSES

Unconjugated hyperbilirubinemia (this is when you’ve too much bilirubin in your bloodstream because it’s not been processed in the liver, as in GS) might happen before bilirubin has entered the liver cells or within the liver cell. If you’ve had an unusual breakdown in your red blood cells then there may be too much of the waste product, bilirubin, for your liver to process as normal.

This will usually result in mild bilirubin elevation, to about 5 mg per dL (85.5 µmol per L), with or without clinical jaundice. The blood might be breaking down because of a number of causes in the blood cells or your enzymes which mean your red cells have stayed alive longer than normal, and built up.  Other causes include autoimmune disorders, drugs, and defects in hemoglobin structure such as sickle cell disease and the thalassemias.

INTRAHEPATIC CAUSES

Un-Conjugated Hyperbilirubinemia Gilbert syndrome is a common, benign, hereditary disorder that affects approximately 5 percent of the U.S. population. It usually results in a mild decrease in the activity of the enzyme glucuronosyltransferase. Gilbert syndrome is typically an incidental finding on routine liver function tests, when the bilirubin level is slightly increased and all other liver function values are within normal limits. Jaundice and further elevation of the bilirubin level may occur during periods of stress, fasting, or illness.

Conjugated Hyperbilirubinemia. Main causes are when there’s a blockage preventing bilirubin from moving into the intestines. Viruses, alcohol, and autoimmune disorders are the most common causes of hepatitis. Inflammation also disrupts transport of the bilirubin and causes jaundice.

Hepatitis A can cause acute onset of jaundice. Hepatitis B and C infections often do not cause jaundice straight away, but can lead to jaundice when chronic infection has led to liver cirrhosis. Epstein-Barr virus infection occasionally causes hepatitis and jaundice that resolve as the illness clears.

Alcohol has been shown to affect bile acid uptake and secretion, stopping the normal flow through the liver. Chronic alcohol use may result in fatty liver (steatosis), hepatitis, and cirrhosis, with varying levels of jaundice. Fatty liver, the most common liver problem, usually results in mild symptoms without jaundice but occasionally progresses to cirrhosis. Hepatitis secondary to alcohol use typically presents with acute onset of jaundice and more severe symptoms.

More rare conditions that can cause jaundice: Autoimmune hepatitis traditionally has been considered a disease that affects younger persons, especially women. Two serious autoimmune diseases that directly affect the biliary system without causing much hepatitis are primary biliary cirrhosis and primary sclerosing cholangitis. Primary biliary cirrhosis is a rare progressive liver disease that typically presents in middle-aged women. Fatigue and itching / skin discomfort are common initial complaints, while jaundice happens later. Primary sclerosing cholangitis, which is also rare, is more common in men; nearly 70 percent of patients also have inflammatory bowel disease. Dubin-Johnson syndrome and Rotor’s syndrome are rare hereditary metabolic defects that disrupt transport of conjugated bilirubin.

Common drugs can also cause problems, such as acetaminophen, penicillins, oral contraceptives, chlorpromazine (Thorazine), and estrogenic or anabolic steroids. Cholestasis can develop during the first few months of oral contraceptive use and may result in jaundice.

POSTHEPATIC CAUSES

Gallstones in the gallbladder are fairly common in adults. Obstruction within the biliary duct system can inflame the gallbladder, and can lead to infection. Cholangitis is diagnosed clinically by the classic symptoms of fever, pain, and jaundice, known as Charcot’s triad. Cholangitis most commonly occurs because of an impacted gallstone, which might then be removed.

Biliary tract tumors are uncommon but serious causes of posthepatic jaundice. Gallbladder cancer classically presents with jaundice, enlarged liver, and a mass in the right upper quadrant (Courvoisier’s sign). Another biliary system cancer, cholangiocarcinoma, typically manifests as jaundice, itching / skin discomfort, weight loss, and abdominal pain. It accounts for roughly 25 percent of hepatobiliary cancers.

Jaundice also may arise with pancreatitis. The most common causes of pancreatitis are gallstones and alcohol use. Gallstones are responsible for more than one half of cases of acute pancreatitis, which is caused by obstruction of the duct that drains the biliary and pancreatic systems.

Evaluation

The initial work-up of the patient with jaundice depends on whether the hyperbilirubinemia is conjugated (direct) or unconjugated (indirect). A urine anlysis that is positive for bilirubin indicates the presence of conjugated bilirubinemia. Conjugated bilirubin is water soluble and so passed through urine.

SO IF YOU’RE JAUNDICED WHAT DO THEY DO TO WORK OUT WHAT’S CAUSING IT? Here’s the clinical information :

BLOOD TESTING

First-line serum testing in a patient presenting with jaundice should include a complete blood count (CBC) and determination of bilirubin, aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transpeptidase, and alkaline phosphatase levels.

Depending on the results of the initial tests, further serum tests or imaging studies may be warranted. The second-line serum investigations may include tests for hepatitis A IgM antibody, hepatitis B surface antigen and core antibody, hepatitis C antibody, and autoimmune markers such as antinuclear, smooth muscle, and liver-kidney microsomal antibodies. An elevated amylase level would corroborate the presence of pancreatitis when this condition is suspected based on the history or physical examination.

IMAGING

Ultrasonography and computed tomographic (CT) scanning are useful in distinguishing an obstructing lesion from hepatocellular disease in the evaluation of a jaundiced patient. Ultrasonography is typically the first test ordered, because of its lower cost, wide availability, and lack of radiation exposure, which may be particularly important in pregnant patients. While ultrasonography is the most sensitive imaging technique for detecting biliary stones, CT scanning can provide more information about liver and pancreatic parenchymal disease. Neither is good at finding stones inside the ducts.

Further imaging that may be done by a gastroenterologist or interventional radiologist includes endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiography.

LIVER BIOPSY

A liver biopsy provides information on the architecture of the liver and is used mostly for determining prognosis. It also may be useful for diagnosis if serum and imaging studies do not lead to a firm diagnosis. Liver biopsy can be particularly helpful in diagnosing autoimmune hepatitis or biliary tract disorders (e.g., primary biliary cirrhosis, primary sclerosing cholangitis).

Glucuronidation – where Gilbert’s Syndrome works in your liver

Glucuronidation
The UGT enzyme that people with Gilbert’s Syndrome are deficient in works in one particular part of your liver and is responsible for the part (or pathway) of your liver’s processing called glucuronidation. Glucuronidation happens when toxins are bound to glucuronic acid which is produced by the liver. Chemicals processed by glucuronidation include morphine, codeine, temazepam, testozterone (Liston, H.; Markowitz, J.; Devane, C. (2001). “Drug glucuronidation in clinical psychopharmacology”. Journal of clinical psychopharmacology).
Some herbal supplements may help glucuronidation (Effects of herbal supplements on drug glucuronidation. Review of clinical, animal, and in vitro studies. March 2011 Mohamed ME, Frye RF.Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, Florida 32610, USA.)The use of herbal supplements has increased steadily over the last decade. Recent surveys show that many people who take herbal supplements also take prescription and nonprescription drugs, increasing the risk for potential herb-drug interactions. In vitro and animal studies indicate that cranberry, gingko biloba, grape seed, green tea, hawthorn, milk thistle, noni, soy, St. John’s wort, and valerian are rich in phytochemicals that can modulate UGT enzymes. However, the IN VIVO consequences of these interactions are not well understood. Only three clinical studies have investigated the effects of herbal supplements on drugs cleared primarily through UGT enzymes. The need for further research to determine the clinical consequences of the described interactions is highlighted.

Essential for Glucuronidation are the nutrients L-glutamine, aspartic acid, iron, magnesium, B3 (niacin) and B6. Thyroid should also be adequate. Cruciferous vegetables (cauliflower, cabbage, cress, bok choy, broccoli and similar green leaf vegetables) are helpful. Glucuronidation efficiency can be improved by calcium-d-glucarate. However, you have to start very gradually with the calcium-d-glucarate, and be very consistent. (http://www.healthyawareness.com/articles/about-autism/phenol-sulfotransferase-and-the-feingold-diet.aspx)

Itching and Gilbert’s Syndrome

Many people who have Gilbert’s Syndrome (GS) experience itching, which doesn’t seem to be related to any obvious cause and has no visible rash.  I myself have been through the obvious checklist many times: washing powder; cosmetics; food; perfume, but nothing had ever changed as, knowing I itch at the drop of a hat, I’m very careful regarding anything I could be allergic to.

BUT…what if it isn’t any kind of allergy?

The idea never occurred to me  until Adina let me know that it was a query that had come up several times with Gilbert’s Syndorme sufferers.  I have had a look at the information available to the general public and here are some of the interesting facts I found on the subject:-

www.nhsdirect.nhs.uk states that “general itching may be a symptom of many conditions, including…some condition affecting your liver…”  The conditions mentioned include more serious liver conditions than GS in terms of prognosis but this doesn’t rule it out as is it not stated that itching is not a GS syptom.

www.netdoctor.co.uk says of primary biliary cirrhosis that the symptoms are identical to any other chronic liver problem – itching aches and low energy.  Chronic means long term, Gilbert’s Syndrome is a chronic liver problem, so again, this is indicative that the itching we experience is a symptom of our GS.

I also found some information on the British Liver Trust website (www.britishlivertrust.org.uk) that may explain WHY itching occurs in GS, through an explanation of a different liver condition:-

Itching is stated as a symptom of cholestasis, which is a reduction in the flow of bile from the liver.  This causes bile salts to build up in the blood, be deposited in the skin and cause itching.  Bilirubin increases are suggestive of problems with the bile duct.  Gilbert’s Syndrome is diagnosed due to a long term increase in bilirubin, also classified as ‘bile level’ in blood tests of liver function.

In Gilbert’s Syndrome bilirubin is raised due to lack of an enzyme rather than a blockage of the bile duct.  It was not clear to me from the information I had found so far if an increase in bilirubin goes hand in hand with an increase in bile salts or whether the two are mutually exclusive.  So I read further…

I found quite a lot of work which links bilirubin and bile salts, for example www.revision-notes.co.uk/revision/859.html , in describing the process of bile secretion, states of bile “It is an alkaline, mucous fluid containing bile pigments, biliverdine and bilirubin.  Bile also contains bile salts…”

 

However, I have not been able to find anything that specifically states that bile salt levels are raised in Gilbert’s Syndrome or whether bilirubin can be increased without bile salts being raised.  It is always stated that of all liver function tests only bilirubin is rasied in GS which suggests levels of bile salts are normal, although I do not know if this is tested separately.  If this is the case it is possible that bile salts may fluctuate, even if within normal limits at testing, causing itching on occasion but not constantly.  This is pure speculation but I hope gives us something to think about and ask our GPs next time we have a consultation.

By contributor Nicola Southworth

The menopause as a trigger of Gilbert’s Syndrome symptoms

One of the major roles of the liver is to process hormones.  It is therefore not irrational to suppose that the menopause may have some effect on a woman’s experience of Gilbert’s Syndrome (and vice versa) due to the enormous hormonal changes and fluctuations that cause it.

During the menopause the ovaries are less able than before to respond to the pituitary hormones follicle stimulating hormone (FSH) and luteinising hormone (LH), and so less oestrogen is produced.  Due to the reduction of oestrogen production some androgens that are still produced by the adrenal glands, such as testosterone, are not overridden as they were before the onset of the menopause.

This means there is a major shift in the balance of hormones in the body, with an increase of FSH, LH and androgens for the liver to process.

Scouring the recently published scientific research I could not find any article that had investigated the effects of these changes on people with liver conditions.  Common sense suggests that these changes would be an immense shock to the liver (we only have to look at all the other effects on the body to understand that this is a huge physical change).  As the liver metabolises hormones and deactivates them when they are no longer useful, it has an increased workload with the excess FSH, LH and androgens.  It seems highly possible that this extra strain on the liver of a GS sufferer would bring to the fore GS symptoms that had not previously been recognised when the liver was used to the hormonal balance of the body.

Many symptoms of the menopause and of GS are very similar and thus these symptoms may be enhanced in the GS sufferer.  For example, the insomnia or disrupted sleep caused by other menopause symptoms, such as hot flushes, can lead to fatigue and generalised aches and pains, common symptoms of GS.  Other symptoms common to both include dizziness and difficulty with cognitive tasks, such as concentration and memory.

Finally, a word about medication.  The most commonly used treatment to ease the effects of the menopause is HRT.  As yet, we are not fully aware of the exact effects many medications have in relation to GS.  We know some medications are processed differently by GS sufferers and so anyone taking any medication who has GS should be aware of this.  There is evidence that HRT can affect bile composition (http://hcd2.bupa.co.uk), which may have implications for GS sufferers.  It may, therefore, be worth being aware of these scant facts when consulting the GP, in order for them to give the best possible advice for the individual.

Unfortunately, as yet, there are no answers to the dual problem of the menopause with GS, apart from the advice AGS passes on to all GS sufferers: to do everything in our power to reduce the workload of our liver

(originally written by contributor Nicola Southworth)

The Liver Fortifying Diet

The liver fortifying diet:

Cut down on the alcohol, salt, caffeine, tobacco, medication, sugar, and fat and stock up on these goodies.  Your liver will love you.

Essential Vitamins and Minerals

Vitamins C and E and minerals zinc and selenium are ‘antioxidants’ shown to aid liver healing. Sources include carrots, tomatoes, peppers, watercress, citrus fruits, berries, wholegrains seeds and oils.

B vitamins and choline are found in egg yolks, liver, legumes and brewer’s yeast and can help liver function.  Make sure your diet contains plenty of green leafy veg rich in folic acid, wholegrains and shellfish rich in vitamin B6, and vitamin B12 foods such as fortified cereals, seafood and seaweed.

 Cruciferous Veg.

Members of the cabbage family have been shown to activate the liver’s cytochrome P450 detoxification process and glutathione conjugation.  In plain English – a process that converts fat-soluble toxins into water-soluble ones, more easy for your body to get rid of.

broccoli cauliflower cabbage

food good for Gilbert's Syndrome

Try include broccoli, cauliflower, kale, mustard greens, radish, brussel sprouts and cabbage in your diet.

Sulphur rich foods.

Garlic, onions, eggs and legumes are rich in sulphur.  They can enhance the sulphuration detoxification process performed by the liver.

Detoxing superfoods.

You should add red fruits, berries, beetroot, and grapes to your diet, as these all help the liver to detoxify and are high in toxin fighting anthrocyanidines.  Papayas and pineapple contain useful enzymes to improve digestion and lemons have a strong cleansing effect.

Helpful Herbs.

Milk thistle, dandelion, turmeric and liquorice have all been shown to aid liver function.  Ginger is also an excellent cleanser.

Good Protein.

The liver needs protein to repair itself, and a diet high in protein gives some people with Gilbert’s Syndrome more energy.  Choose healthy alternatives to red meat such as fish, nuts, pulses and seeds as they are easier to break down and place less of a burden on your liver.

Water.

Once your liver has removed the toxins from your body, you must flush them out of your body.  The only way to do this is to drink lots of water.  Three pints or eight glasses a day minimum!  Although you may find this no problem as some sufferers have expressed how thirsty they seem these days.

itchy skin

Do you find a side of effect of your GS is itchy skin?  A lot of us experience it.  One suggestion why this might happen is that your skin, as the bodies 2nd largest detoxification organ after your liver, is trying to help your ailing liver in the detox process.  Here’s a couple of tips that might help – 1) Skin brushing before your morning shower or bath helps to stimulate circulation and encourage detoxification.  Brush towards your heart using firm strokes. 2) If you’ve over indulged and your liver is struggling, swapping your morning-after coffee with a cup of nettle or dandelion tea will replace lost minerals and support your liver’s detoxification process.