From Greek, kyrròs, which means yellow, and is a pathologically well-defined
morbid condition, alcoholic cirrhosis is historically known as cirrhosis of
Laennec, and is the most frequent type found, characterized by a thin and
diffused fibrosis, with uniform loss of hepatocytes , called alcohol cirrhosis;
the three forms of alcoholic liver disease are: alcoholic steatosis, alcoholic
hepatitis and alcoholic cirrhosis.
The clinical feature of cirrhosis, in general, is associated with disparate
systemic manifestations, which have been widely discussed in this website and
which are summarized below in this list:
- anasarcatic state (ie generalized edema and lower limbs)
Spider nevi, or stellar angioma that appears in
cirrhotic patients, on the skin of spots or reddish
spots from the shape attributable to that of a spider's
web, such as arterio-venous fistulas.
- eritemi
- angiomas
- gynecomastia (both for antialdosteronic therapy and for failure to inactivate
sex hormones)
- jaundice
- thrombocytopenia
- hepato-renal syndrome (ie renal failure of the liver, with severe
hyponatraemia and hypercreatininemia)
- porto-systemic encephalopathy
- coagulation alterations
- dysrotidemia with hypoalbuminemia
- circle of esophageal, gastric, hemorrhoidal, caput medusae, hypogastric, etc.
- ascites
It is characterized by an alteration of the hepatic parenchyma which is
subverted by a series of noxae, as explained below, with the result that it is
replaced by regeneration nodules and fibrous tissue; in other words, from an
insult, viral, toxic or alcoholic, it derives a tissue damage and an
inflammatory reaction, with production of fibrous tissue.
It is characterized by an alteration of the hepatic parenchyma which is
subverted by a series of noxae, as explained below, with the result that it is
replaced by regeneration nodules and fibrous tissue; in other words, from an
insult, viral, toxic or alcoholic, it derives a tissue damage and an
inflammatory reaction, with production of fibrous tissue.
An ascitic patient
Not always cirrhosis depends on alcohol or hepatotropic viruses, since other
noxae (ie literally from the Latin causes that harm the liver) can give a
picture of cirrhosis of the liver, even a hepatic stasis of circulation, since,
as we know, the blood captured from the portal system of intestinal origin, it
is detoxicated by bacterial toxins, ammonia from the intestine and filtered by
nutrients from the hepatic circulation and, therefore, reaches the great venous
circulation through the suprahepatic veins. It may happen that the heart is
deficient as a pump in its ability to "suck" the caval blood and, consequently,
this causes a slowing down of the circuit and a "stasis liver" or "nutmeg" liver
of the classical anatomopathological classification.
- Alcoholic cirrhosis (very frequent)
- Cryptogenic cirrhosis (that is, the cause is unknown), today it is thought
that the NASH syndrome finally ends up in the last anatomical pathology of
cirrhosis.
- Spider nevi, or stellar angioma that appears in cirrhotic patients, on the
skin of spots or reddish spots from the shape attributable to that of a spider's
web, such as arterio-venous fistulas.
- Metabolic cirrhosis (ie due to errors of metabolism with accumulation of toxic
substances in the liver)
- Cirrhosis from drugs (eg that of the anesthetists of the past, I knew a
colleague suffering from cirrhosis from anesthetic gases) and from toxic
substances
- Post-viral cirrhosis (very frequent)
- Primitive biliary cirrhosis
- Liver cirrhosis of autoimmune hepatitis
Are you sure you are not experiencing a hepatocellular carcinoma?
You dosed the alphafetoprotein, did you run an abdomen echo?
In the past, not knowing the importance of hepatitis B and C viruses, it was
thought that the most common cause was alcoholismochronico (alcoholic cirrhosis).
Now we know that alcoholism can lead to alcoholic cirrhosis, but even more
frequently it is an aggravating contributing factor of pre-existing (often
unknown) chronic viral hepatitis B or C. In fact the alcohol abuse is able to
halve the time of occurrence of cirrhosis in a patient already suffering from
chronic viral hepatitis (from about 20-30 years to 10-15 years). Particularly as
regards alcohol, it is considered potentially harmful to take more than 50g of
alcohol per day for several years.
From the anatomopathological point of view, according to the etiopathogenetic
mechanisms, we can divide the cirrhosis into:
- Atrophic cirrhosis, classically that of Laennec, in alcoholism, in which the
mechanism of fibrogenesis prevails over that of nodular regeneration. atrophic
cirrhosis of drinkers or vulgar cirrhosis. It consists of a process with a
progressive course, which culminates in the shrinking or atrophy of the organ,
which can lose up to almost two thirds of its weight.
- Hypertrophic cirrhosis, in those forms in which the mechanism of regeneration
prevails
There are other forms of cirrhosis, equally producing ascites, although less
rapidly and less regularly, or sometimes decorrent without ascites, with less
severe symptoms of liver failure and therefore of a more benign prognosis, in
which the liver remains hypertrophic (hypertrophic cirrhosis) simple by Hanot
and Gilbert). Some authors also admit the dyspeptic hypertrophic cirrhosis (Budd
cirrhosis), due to toxic substances, originating from alterations of the
digestive processes. It should also be noted the form of malignant hypertrophic
cirrhosis of malignant Hutinel and Sabourin, which is noted above all in
tuberculosis subjects, and in which the malignancy of the process is due to the
profound degenerative changes of the parenchyma and therefore to the marked
degree of hepatic failure. Another variety has been isolated by Gilbert, Garnier
and Castaigne, under the name of diffuse hypertrophic cirrhosis.
The decrease in liver function leads to complications such as:
- formation of liquid at peritoneal level (ascites)
- formation of collateral venous circles. These may be superficial, and be
visible on the abdomen, or cover the veins at the junction between the esophagus
and the stomach. The breaking of these last varices is a feared and dangerous
event for the life of the subject.
- hepatic encephalopathy, which manifests with mental confusion and drowsiness,
up to coma
- hepatorenal syndrome, characterized by a rapid deterioration of renal function
- hepatocellular carcinoma, a frequent cause of death in cirrhotic subjects, why
these are subjected
For cirrhosis, currently, there is no therapeutic outlet, the only one is represented by liver transplantation: it is the result of all liver noxas on the liver: toxic, viruses, toxic industrial, eg. carbon tetrachloride. The reparative mechanism of liver injury at liver level is very similar to that of other tissues: the mechanisms are identical. ITO cells, or stellate cells, are responsible for hepatic fibrosis, are similar to the mesangial cells of the kidney or fibroblasts of the lung. In 1980 it was discovered that ITO cells form collagen; they are pericitis, that is, they have potential contractile. Surround the capillary endothelium and are extension of smooth muscle cells, accounting for 15% of the liver cell population. But to get to the cirrrosis there are numerous cells involved in the repair of the damage; endothelial cells, pericitis and macrophages. Stellate or ITO cells are transformed into myofibroblasts. The accumulation of infiltrates is modest for Wilson and hemochromatosis. The next point is the alteration of the extracellular matrix that contains collagen fibers. ITO cells are rich in fat and vit. A, lose fat and retinoids: step 1 for transformation into myofibroblasts is this event. Then there is the contraction of the excess matrix. The extracellular matrix has a different amount of collagen: type IV in the Disse, the III around the vessels: the low-density matrix turns into a high-density matrix and produces dense collagen fibers. The quantity and quality of the matrix increases 3 times and increases the 1st type at the expense of the IV, the cells secrete collagen and particular proteins: proteases for a physiological defense; the same cells that synthesize collagen produce MMP Metalloproteinases, that is, on the one hand they increase the synthesis but on the other side they destroy the collagen. TIMPs are inhibitors of these enzymes; there are 18 types of collagen; there are the proteoglycans, the interstitial collagen of the capsule and the large vessels that are of type 1 and 3 .. In the space of the Disse the first modifications occur: with reduction of microvilli and fenestration of the endothelium with imbalance in the passage of substances from the hepatocytes to the space of the Disse and this promotes the transformation of the liver into cirrhosis. The factors that reshape are the MMP1 and MMMP2, high or low density and then inhibitors. Proteases are produced by Kuppfer cells but also by those of ITO. Therefore a substance is needed that acts on inhibitors or on MMP1. The key point is the activation of ITO cells in myofibroblasts, with loss of the deposition of Vitamin A, and release of PGDF, cytokines of inflammation. However the administration of vit. A in vitro causes a reduction in the transformation but not in vivo, on the contrary it is toxic. The VITA + tetrachloride experiment does not reduce the toxicity of the latter. The starting point could also be in endothelial cells that produce fibromionectin, with alteration of the extracellular matrix. The other point is the same hepatocytes through the formation of aldehydes, lipid peroxidation with membrane destruction. So the transaminases are the indicator of the formation of peroxides and aldehydes. This alteration here depends on the NFKB or nuclear factor that is produced by peroxide and aldehyde insult with action on Kuppfer cells and ITO cells stimulation of substances in the nucleus and production of cytokines which results in transformation into myofibroblasts. Kuppfer cells determine the excitation of ITO cells as well as platelets that produce TGFbeta1, a factor determining fibrosis. So the platelets produce cytokine; next to the pro-inflammatory cytokines
- CITOCHINE.
- TNF, Interferon beta, adhesion molecules;
- OXIDATIVE STRESS.
It is the imbalance between production of oxidizing substances and the scavenger
mechanisms, the defensive system comes to fall; there is a class of chronic
non-viral inflammatory diseases; for example diabetes with its dysmetabolism,
where there is a reduced scavenger activity, with an increase in triglycerides
and hypercholesterolemia is at the base. In fact, alcohol-dependent subjects at
60-70 g / day of alcohol may develop cirrhosis due to personal reactivity.
After initiation there is perpetuation, chemotaxis, fibrogenesis, retinoid
losses, transformation of stellate celules into myofibroblasts. by action of the
PDGF.
- contractality: ET-1 or endothelin, or hypertensive substance.
- nitric oxide.
- Fibrogenesis-> TGF transforming grow factor -
In the experimental animal HGF or hepatocitis grow factor.
Another concept is on the TH1 and TH2 where the helper T synthesize IFNgamma and
IL2 the TH2 instead IL5 -IL -IL-13
Sometimes the diagnosis is made by chance, during random instrumental investigations, for example an ultrasound of the abdomen; at other times, given the history of chronic hepatitis related virus, the last picture of cirrhosis emerges. Upon inspection, an increase in the volume of the abdomen can be objected, with the finding of a liver of increased size, which extends below the right rib arch, on a line called "emiclaverare", that is conducted from the middle of the clavicle, to descend, perpendicular to it, up to the liver, which technically describes overflowing "a finger, two transverse fingers ..."; it is a simple and ancient way that the old clinician uses, or in centimeters or, better, through the ultrasound survey or, more simply, with the old system of percussion with the fingers, and the observation of the obtuse "thigh" sound, where it is the hepatic parenchyma; the liver can be painful, if the glissoniana is extended, or it is possible to palpate a painful and painful gallbladder along the hepatic border; the liver will be of increased consistency, until it perceives the margins bozzuti and hard, almost woody.
There may be other manifestations, including ascites, see the link, or changes in the circulatory system such as star angiomas, or other elesions: the snow spiders. In severe cases, the ascitic fluid, called "spontaneous bacterial peritonitis" may appear, as the opsonin activity of the liver is reduced in these patients. We refer to the activity of the Kupffer cells, the macrophages, which purify the portal blood from the intestinal bacteria and this can be a very serious sign of the continuation of the disease, which can easily lead to the exitus a defunct patient. Still the portosystemic encephalopathy, failing the detoxifying capacity of the liver in the riguradi of ammonia produced by the intestine is at the base, for reasons already described in this website, of a malaise of the patient with consequent coma status.
Who writes has often managed this type of patients, through intravenous therapy with branched amino acids, followed by selective ones, in addition to 33% glucose, medicated, if necessary, with insulin, in order to allow the "penetration" facilitated of amino acids through the blood-brain barrier, in order to activate the CNS depressed by the false neurotransmitters (see etiopathogenesis of encephalopathy). Still the medical hepatologist is fought by the need to balance the right diuretic therapy of these cirrhotic subjects in the phase of ascitic decompensation, with the need not to generate an encephalopathy, balancing, if necessary, the values of plasma albumin, regulating the vitamin K antihaemorrhagic and using potassium-sparing diuretics.
The laboratory meets the clinician through the alteration of routine bioumoral parameters, the so-called "hepatic profile", ie a series of investigations such as AST, ALT, YGT, alkaline phosphatase, coagulation, iron, cupremia, protidogramma, albuminemia, blood count that give an idea about the stage of the disease. The levels of AST are disproportionate to those of ALT for which the AST / ALT ratio is> 2, contrary to viral hepatitis.
Prothrombin time is the most precise expression of the residual protidosynthetic capacity of the liver is always reduced, in the most advanced stages, generally around 50-60%, as well as the values of albumin. In addition, a polyclonal hypergammaglobulinemia is shown at the protidogramma, not to be confused with the "monoclonal" one of multiple myeloma. The dosage of alpha fetus protein allows me to monitor or orientate myself if there are suspicious lesions for primary liver lesions or hepatocellular carcinomas. It is also important to require frequent controls on the values of azotemia, creatinine and sodium and blood potassium, especially during therapy with loop diuretics and antialdosterones.
It is an art, in the hands of the hepatologist or the expert internist. Never in the wrong hands! It makes use of loop diuretics, with a watchful eye for hyponatremia and hyperkalemia, when exaggerating with furosemide or potassium canrenoate and antididosterones. It is completed with the use of a hypodermic, hypercaloric diet, enriched with anti-haemorrhagic vitamin K (eg Konakion drops), at least 1 gram of protein per kg / weight, with branched chain amino acids, polyvitamins (for example in the alcoholic patient with Wernicke-Korsakoff disease); it is necessary to abolish alcohol, through a psychological support therapy (but are there good psychologists from you?), or with antidepressants, benzodiazepines if it is possible to use them because of the poor hepatic capacity to detoxicate the organism; also eye to paracetamol which has toxic action and to drugs in general, which have hepatic excretion. In the early stages of the disease, the therapy is based on the removal of risk factors and etiologic agents (abstention from alcohol, anti-viral therapy for viruses B and C) and in a balanced diet that aids the regeneration of the liver; it is also necessary a pharmacological therapy that reduces the risk of complications, in the case, for example, of varices secondary to portal hypertension. The complications of cirrhosis of the liver are treated with specific therapies, pharmacological and non.The patient suffering from decompensated liver cirrhosis, when limited in self-sufficiency, can be treated at home with home liver care.