the patient's yellow!

notes and personal reflections dr. Claudio Italiano, hepatologist

The information contained in this site are only of scientific value, none can automedicarsi referring to the contents of my Your Website. Everyone should consult their doctor for treatment!


All you ever see a person suddenly has yellow eyes and sallow skin. This is a very important symptom that deserves the attention of the doctor immediately! So if you have these symptoms, contact your doctor immediately and ask the appropriate investigations comparing the link below the profile reported liver also also challenged all these links in terms of liver disease, but not excluding, in cases of jaundice, cancer pancreas, which is a possible cause of jaundice and gallstones in bile and, therefore, its treatment and considered diseases of the liver associated with alcohol such as cirrhosis, acute hepatitis (see Autoimmune Hepatitis Hepatitis A Hepatitis Hepatitis B C) and primary biliary cirrhosis:

jaundice and ascites albumin use in clinical

Profile hepatic albumin treatment of ascites albumin and its functions

Bilirubin is responsible for yellowing (jaundice, jaundice) of mucous membranes and skin in case of:

bilirubin bilirubin overload causes extra and intraglobulari (eg hemolysis of red blood cells, anemia cf)

bilirubin because the liver captures syndrome (Gilbert and Crigler-Najjar, see jaundice)

bilirubin-related causes its failure to remove the liver and accumulation in the body (eg. viral hepatitis (see Hepatitis A Hepatitis B Hepatitis C), cirrhosis, sclerosing cholangitis, primary biliary cirrhosis, hepatitis, pregnancy, cancer of the pancreas head with obstruction from compression of the bile duct, calculi of the bile duct, cancer of the papilla of Vater, etc.. etc.).

So the first thing to consider is that of whether the bilirubin is direct or indirect:

direct or married if their share is larger comes from the liver, where it is conjugated ac.glicuronico for excretion of liver disease and / or biliary obstructions (see profile liver);

unconjugated or indirect, that comes from red blood cells from hemoglobin being converted into bilirubin, such as the crisis of hemolytic anemia, or because the liver is unable to capture and dispose (jaundice).


Structure of bilirubin:

It 's a linear tetrapyrrole, resulting from the opening of cyclic tetrapyrrole protoporphyrin IX from hemoglobin to a broken bridge metin. E 'characterized by H + intramolecular bonds between COOH and NH groups with total loss of solubility in H2O and acquisition of high solubility in non-polar solvents and lipids. After exposure to light between 400-500 nm is determined photoisomerization, ie beyond the normal isomer ZZ isomers are created ZE, EZ, EE, with different configurations of planar H + metin bridges linking the pegs and therefore more soluble in the solvents-aqueous ( this is exploited nell'ittero neonatal physiology, with exposure to UV light). Esterification in the liver occurs mainly with glucuronic radicals at the carboxyl side chain propionate with increased water solubility and reduction in intestinal. Bilirubin diffuses rather easily at the level of blood-brain barrier, placenta and intestinal mucosa.

Source bilirubin:

The average daily production is 250-350 mg/24 h resulting from the demolition of the ring during the hemoglobin prosthetic process emocateresi system-level grid and histiocytic tissue catabolism of heme proteins, cytochrome P450, myoglobin, heme enzymes .

1) The first stage of the formation of bilirubin from hemoglobin is to start posting heme from globin, the latter will undergo a gradual integration of hydrolysis products in the pool of amino acids;

2) dell'emeossigenasi microsomal action that requires 3 molecules of O2 per mole of heme degradation and availability of NADPH-cytochrome c reductase in microsomal heme to suffer the pyrrole ring opening in the bridge-alpha metin central; forms a central tetrapyrrole with Fe + + (biliverdin-Fe + +), this will result after the detachment of the iron biliverdin.

3) action of NADPH-biliverdin reductase, resulting in the reduction of biliverdin to bilirubin.

The heme-oxygenase system is thus three distinct enzymes: two microsomal, heme-oxygenase and biliverdin reductase. The metabolic capacity of this system is very high and is further enhanced in the states iperemolitici. The activity of this system is modulated by various hormones, including glucagon, catecholamines act by inducing the formation of cyclic AMP nell'epatocita.

Transport of bilirubin.

Bilirubin binds to albumin in the circulation radicals histidine, arginine and tyrosine, the dimension bound and free quota set a hemodynamic balance; the free quota can penetrate the blood brain barrier in early life, settling in the basal ganglia in the first stages of life.

Conjugated bilirubin is also conveyed by albumin but with lesser affinity so that in the glomerular capillaries spreads in urine.

Hepatic uptake

Removing bilirubin from the circulation is rapid, through an albumin binding to specific receptors located on the membrane to the sinusoidal side. The receptor migrates to the cytoplasmic surface, this receptor is likely a membrane protein of 60,000 daltons. Bilirubin in the cytoplasm contracts a binding protein fractions present in the cytosol, the protein ligandina or Y or glutathione-S-transferase B with a molecular weight of 47,000 daltons, composed of two subunits A and B of 22,000 and 25,000 daltons, joined by two disulfide bridges and protein Z, weighing 11,000, the first transports bilirubin and other organic anions and the second also ac.grassi long chain, the latter the binding of bilirubin is possible especially in case of saturation of Y or to prevent reflux into the sinusoid of bilirubin.

Conjugation of bilirubin.

The process of conjugation takes place in REG and REL and delivers a water-soluble compound that can be excreted in bile. Is the dominant mode of conjugation with glucuronic acid and leads to the formation of derivatives and mono diglicuronoconiugati. Under normal conditions the esterification of propionic carboxyl occurs with the hydroxyl in position 1 glucuronic acid. The process of conjugation is catalyzed by a UDP-fosfoglicuronil-transferase, located at the membrane of both smooth and rough endoplasmic reticulum. Takes place in two stages:

1) monoglucuronide bilirubin, 2) bilirubin diglicuronide the esterification of propionic central second chain, or 2 molecules can merge monoglicuronide releasing a molecule of free bilirubin, a reaction catalyzed by a dismutase, bilirubin-glicuronoside-glicuroniltransferasi.

The conjugated bilirubin is then excreted in bile dell'epatocita pole. Able obstacle to the excretion part of conjugated bilirubin can be eliminated through the sinusoidal pole and return to the systemic circulation to be eliminated by the kidney, so the urine assume in this case, an intense color (urine marsala "of 'hepatitis).

.
Excretion of bilirubin in the bile.

The conjugated bilirubin is excreted through the canalicular membrane dell'epatocita. This is probably an active process, mediated by membrane carriers used by other anions such as BSP, indocyanine green, contrast media), a mechanism that requires energy. The conjugated bilirubin excreted almost certainly less than 1%. The gastrointestinal tract is hydrolyzed by bacterial beta glucuronidase in the colon and terminal ileum, producing tetrapyrroles indicated by the term bilinogeni (uro, meso stercobilinogeno) that are excreted in faeces in amounts of 200-300 mg / day. The urobilinogen are oxidase in Bil'in and excreted in faeces and a part (20%) is reabsorbed in the gut, transported to the liver and excreted in the bile. A portion that escapes hepatic uptake is filtered through the renal distal tubule and excreted in the urine, urobilinogen equal to 2-4 mg / day. The determination of serum bilirubin, and bilin bilinogeni of urinary allows accurate assessment of bilirubin metabolism.

Serum bilirubin: normal values: 1 mg TOTAL%

INDIRECT 0.7 -0.8%

DIRECT 0.2%

Urinary bilirubin: normal values: ABSENT (that share is insoluble indirect)

If there is bilirubinuria means that conjugated bilirubin and hepatic escaped the filter has been exceeded the capacity of renal tubular resorption (urine "marsala").

Urobilinogenourinario: normal values: 0.2-0.3% (proportion that escapes the liver during enterohepatic circulation)

If these values increase means: 1) increased production of bilirubin, slowed intestinal transit, bacterial overgrowth in the small intestine, and in all liver diseases that interfere with the normal uptake urobilinogen (acute hepatitis see Hepatitis A Hepatitis B Hepatitis C, cirrhosis , cholestasis in pregnancy)

Fecal urobilinogen: normal 100-200 mg / day, increasing to overproduction of bilirubin, decreases in biliary obstruction (feces or ipocoliche acholic).

Classification of jaundice:

.
Jaundice-preepatico

-Hepatocellular Jaundice

-Post-hepatic jaundice

In the first case, preepatici for jaundice, the cause is before the liver, ie a much too bilirubin for hemolysis, sideroblastic anemia, thalassemia, sickle cell anemia (see anemia in Part 2), etc..;

In the second case, for hepatocellular jaundice, we will:

-S. Gilbert: with indirect bilirubin of 1.5 to 6 mg / dl, and lack of glicuroniltransferasi uptake and transport of bilirubin. The diagnosis is made with the proof of fasting for 36 hours, and increased bilirubin x 2 times, and proof of the BSF in the standard, while the loading test with unconjugated bilirubin is impaired;

-S. Crigler Najjar type II and type I deficiency for all or part of glicuroniltransferasi, urine does not have stains, but the stools are ipocoliche, the indirect bilirubin, between 15 and 25 mg / dl and 6.12 mg / dl; load with BSF is normal;

-S. Dubin-Johnson and Rotor, jaundice with bilirubin are mixed, the Dubin Johnson has abnormal loading test of unconjugated bilirubin with regurgitation of conjugated bilirubin, and also test the BSF;

-S. Rotor: The BSF test with no regurgitation liver at 90, although the uptake is reduced and the liver does not appear with Tc-HIDA;

-S. Summerskill-Walshe of intrahepatic cholestasis or benign applicant: unknown pathogenic factor, is characterized by tendency to cholestatic syndromes triggered by several factors: gestational jaundice, estrogen episodes spring and autumn, probably related to antigen-antibody reactions and immune complexes.



Third cases, jaundice hepatitis post, think of an obstructive defect, intra-or extrahepatic, ie at a standstill excretion. WARNING! because if the conjugated bilirubin level rises suddenly need differential diagnosis with acute viral hepatitis see Hepatitis A Hepatitis B Hepatitis C, drug-induced hepatitis or biliary obstruction in the course of carcinoma of the head of the pancreas, or odditis, papillitis, sclerosing cholangitis, cirrhosis biliary, simple alcoholic cirrhosis, the main bile duct stones and see the treatment of calculi of the bile duct etc.. Will be useful in these cases, ERCP, or retrograde cholangiography perendoscopica with the study of cancer through indirect specular imaging of the biliary tract.

Diagnostic functional impairment.

The diagnosis must be understood as functional diagnosis of diseases. To assess hepatic function is difficult given the variety of liver functions and requires a large number of investigations, has come to define the clinical and biochemical syndrome, that is associated with clinical laboratory tests: they are 5:

- The syndrome of biliary retention;

- The s. hepatocellular insufficiency;

- S. hepatocyte necrosis;

- The s. by acute inflammation

- The s. subacute chronic inflammation with infiltration by mesenchymal.

Therefore, a epatopaziente will present one or more abnormal laboratory tests to be framed in such syndromes.

Bile retention syndrome is characterized by increased bilirubin glucuronic, colalemia bilirubinuria and increased with FA, if it arose recently parenchyma is spared;

The hepatocyte failure syndrome is characterized by a reduction in the metabolic functions of the liver with a reduction of albumin, fibrinogen, because these substances are created by the liver and so on.

Necrosis syndrome is given by the destruction of cells with cell death and significant rise in transaminases and other enzymes such as Ornitilcarbamiltransferasi, OCT, SDH sorbitol dehydrogenase in the cells;

The syndrome of acute inflammation with elevated ESR and the fraction range of IgG;

The syndrome of subacute inflammation with mesenchymal activation and increased gamma globulin, especially IgG.

The specialist must use the most useful tests to arrive at the definition of the syndrome biohumoral.

STUDY OF FUNCTION PROTIDOMETABOLICA.

Includes the determination of the total protein and surrounding villages, one important thing is that albumins are the exclusive relevance liver while antibodies have a different origin; The hypoalbuminemia (cf. albumin, liver profile) may depend on: 1) reduced hepatic synthesis or 2 ) loss with increased kidney in cirrhosis are lost for stasis through the digestive system, decreased albumin in chronic hepatitis and the degree of hypoalbuminemia increases with the disease. Even the increase in gamma globulin for chronic activation of mesenchymal and increased autoantibodies, with increased gamma globulins of different classes, MA and G in the early stages but the increase is borne by IgM then IgG, IgA increased in cirrhosis, for it is possible to tell whether the liver has recent origin (IgM) or chronic onset (IgA and IgG) may also seek autoantibodies ANA, SMA or antimuscolo smooth, hip or anticitoplasma. Other tests include the determination dell'aptoglobina whose dosage is between 0.5 and 1 mg and decreases until it disappears in relation to liver damage. An increase of IgG autoantibodies may correlate to the increase.

Further investigation is needed because the study dell'ammoniemia rapid implementation, the NH3 is a product of protein degradation and elimination is the liver and also the ammonia is indicative of functionality.

The most important thing is the prothrombin complex and may depend on the Vitamin K, which considering the prothrombin time, which depends on the factor V, VII and X are vitamin. K employees can determine whether the defect is hepatic or nutritional deficiency, which shall be by administering Vitamin K nell'epatopaziente but the synthesis is still low.

THE STUDY OF LIVER FUNCTION glycometabolic

The liver is the storehouse for the glucose that is stored as glycogen. We have seen that in chronic liver diseases has increased disposal of glucose with increasing glucose, wherein epatopazienti have diabetes. There is a test load with galactose or Bauer you in the mood and look in the urine to see if the liver can incorporate galactose, so if the quantity is greater than 5% means that there is liver failure to store. Lipid metabolism: measurement of fractional cholesterol, ie esterified fraction because it is the liver that esterification.

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