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Jaundice

Category: Illness or disabilities

Type

Involuntary

Introduction and description


Jaundice caused by hepatic failure.  Photo from Wikipedia

Jaundice is a condition that  produces yellowish pigmentation of the skin, the whites of the eyes, and other mucous membranes. The term jaundice comes from the French word jaune, meaning yellow. 

Cause

Jaundice is caused by ‘hyperbilirubinemia’  - increased levels of bilirubin in the blood. This in turn causes increased levels of bilirubin in the extracellular fluid.   The concentration of bilirubin in blood plasma does not normally exceed 1 mg/dL (>17µmol/L), but once it gets higher than 1.8 mg/dL (>30µmol/L) jaundice results.

Jaundice itself is not a disease, but rather a sign that something has gone wrong in the normal metabolism of bilirubin.

When red blood cells have completed their life span of approximately 120 days, or when they are damaged, their membranes become fragile and prone to rupture. It is the immune systems’s job to handle red blood cells that are ‘past their sell by date’ so when the blood cells pass through organs like the spleen the cells rupture and the immune system kicks in to handle the contents.

Cellular contents include haemoglobin.  The haemoglobin is processsed by macrophages from the immune system, and split into its heme and globin portions. The globin portion, a protein, is degraded into amino acids and plays no role in jaundice. Two reactions then take place with the heme molecule.

First, the heme is processed by an enzyme ‘heme oxygenase’ and the result is the substance  biliverdin (green color), iron and carbon monoxide. Second, the biliverdin is reduced to the yellow coloured  bilirubin by another enzyme called  ‘biliverdin reductase’.

It is worth adding that the majority of bilirubin comes from the breakdown of heme from expired red blood cells in the process just described. However approximately 20 percent comes from other heme sources.

The bilirubin then travels to the liver through the bloodstream. Once it arrives at the liver, it is mixed with ‘glucuronic acid’  to form ‘bilirubin diglucuronide’ also known as "conjugated bilirubin", which is water soluble.

This conjugated bilirubin is excreted from the liver into the biliary and cystic ducts as part of bile. Intestinal bacteria convert the bilirubin into ‘urobilinogen’. From here the urobilinogen can take two pathways. It can either be further processed and passed out in the faeces, or it can be reabsorbed by the intestinal cells, transported in the blood to the kidneys, and passed out in the urine.

So what can go wrong to cause jaundice? 

When a pathological process interferes with the normal functioning of the metabolism and excretion of bilirubin just described, jaundice may be the result.

Jaundice is classified into three categories, depending on which part of the physiological mechanism the pathology affects. The three categories are: 

Category

Definition

Pre-hepatic/ hemolytic

The pathology is occurring prior to the liver.  Pre-hepatic jaundice is caused by anything which causes an increased rate in the breakdown of red blood cells –  for example, malaria,  sickle cell anaemia, spherocytosis, thalassemia, diseases of the kidney.

Hepatic/ hepatocellular

The pathology is located within the liver.  Hepatocellular (hepatic) jaundice can be caused by liver disease - acute or chronic hepatitis, hepatotoxicity, cirrhosis, drug induced hepatitis, liver cancer and alcoholic liver disease. Cell death reduces the liver's ability to metabolize and excrete bilirubin leading to a buildup of unconjugated bilirubin in the blood.

Post-Hepatic/ cholestatic

The pathology is located after the conjugation of bilirubin in the liver.  Post-hepatic jaundice, also called obstructive jaundice, is caused by an interruption to the drainage of bile in the biliary system. The most common causes are gallstones in the common bile duct, and pancreatic cancer in the head of the pancreas. Also, a group of parasites known as "liver flukes" can live in the common bile duct, causing obstructive jaundice. Other causes include strictures of the common bile duct,  pancreatitis and pancreatic pseudocysts.

Symptoms

Apart from the very obvious yellowish pigmentation of the skin, the whites of the eyes, and other mucous membranes; jaundice can be characterised by the presence of pale stools and dark urine.

When this occurs, it suggests an obstructive or post-hepatic cause as normal faeces get their colour from bile pigments. However, although pale stools and dark urine are a feature of biliary obstruction, they can occur in many intra-hepatic illnesses and are therefore not a reliable clinical feature to distinguish obstruction from hepatic causes of jaundice.

Patients can also present with elevated serum cholesterol, and often complain of severe itching or "pruritus" because of the deposition of bile salts.

No single test can differentiate between various classifications of jaundice. A combination of liver function tests is essential to arrive at a diagnosis.

The pathology of jaundice-related renal insufficiency: cholemic nephrosis revisited
- Betjes MG, Bajema I ; Division of Nephrology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
The spectrum of jaundice-related nephropathy can range from limited proximal tubulopathy to renal failure. The latter condition was known as cholemic nephrosis in the early literature on this subject.
Elevated plasma concentrations of bile salts and bilirubin conjugated or not, putatively mediate the nephrotoxicity. A functional derangement of renal tubule cells is considered to underlie the nephropathy, but published data on renal histology are scarce.
In this report, we describe the renal biopsies of two jaundiced patients with reduced creatinine clearance, and we critically review the literature on the pathogenesis of jaundice-related nephropathy.
Normal renal architecture, indicating functional renal impairment, and extensive renal tubule necrosis were both observed in jaundice-related renal failure. The findings fit the original description of cholemic nephrosis. Both bilirubin and bile salts are potential nephrotoxins in animal models, but their precise role in the pathogenesis of jaundice-related nephropathy is not known. Patients with bilirubin plasma concentrations >20 mg/dL, a low serum albumin concentration or endo-toxemia, could be more prone to develop renal failure due to jaundice-related tubulopathy.
In conclusion, jaundice-related nephropathy is essentially a tubulopathy, but the exact nature of the Pathogenesis is still uncertain.

How it works

The cause of the spiritual experience is ultimately linked to the cause of the jaundice.  Thus it may be related to liver disease, kidney disease, parasites - the presence of liver flukes, and so on.

Follow the relevant links to see the cause.

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