ACUT AND CHRONIC LIVER FAILURE

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ACUT AND CHRONIC LIVER FAILURE
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Acut liver failure

• Liver failure several hours or days after the
  damageing insult. The main problem is the death
  of the hepatocytes especially by necrosis.
• Types
• simple hepatitis only liver is damaged (good
  recovery)
• fulminant and subfulminant liver failure after
  and becuse of the liver damage the other organs
  are unfunctional brain ( hepatic
  encephalopathy), cardiorespiratory, urinary and
  different infections. (recovery 40, 20)

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• Histological alterations
• necrosis and apoptosis cell death
• regenerative islands with new cells
• inflammation ( hepatitis) by the infiltration of
  leucocytes, macrophages
• steatosis accumulation of TAG
• fibrosis connective tissue increase
• Causes of acut liver failure
• chemicals, medicines, organic solvents, ethanol,
  plant and fungi toxins (60)
• illness of other organs (18) portal thrombosis,
  heart failure
• viruses (12) Hepatitis A,B,C,BD, E,F,G,
  Cytomegalov., Varicella zoster,
  Adenov., Eppstein-Barr v., Q-fever,
  Yellow-fever
• systemic sepsis...
• metabolic

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Among all the acut liver failure
phenacetin/paracetamolacetaminophen causes 37
(according to a study in USA) Signs of acut
liver failure functional hepatocyte number ??
glycogen storage and gluconeogenetic capacity
?? hypoglycemia, lactacidosis bilirubin is not
conjugated in liver, rather accumulated in sclera
and skin ? icterus blood clotting factors,
inhibitors, fibrinolytics are not produced by
liver ? coagulopathy bleeding and hemorrhage at
the same time urea cycle does not proceed ?
hyperammonemia ? hepatic encephalopathy Treatment
glucose insulin fulminant failure mannit,
hemofiltration, help of the cardiovascular system
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Chronic liver failure

• Because of prolonged insult of liver it proceeds,
  worsens slowly. Liver normal structure is
  disrupted, something abnormal is accumulated and
  accompanied by inflammation.
• inflammatory cells (leucocytes, lympocytes,
  macrophages) that produce cytokines, hepatocytes
  die (and regenerate) hepatitis
• TAG triglyceride accumulation steatosis
• connective tissue, collagen accumulates and
  appears where it was not normally cirrhosis (
  continuation of fibrosis)
• immortalized tumor cells spred carcinoma
• bile acids hyperproduced but remain in liver, not
  secreted cholostasis, cholangitis
• Any of them can be combined. (E.g.
  hepatosteatitis, biliary cirrhosis, Hepatitis
  C infection leading to carcinoma)

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• Reasons of chronic liver failure
• overfeeding, obesity, insulin resistance,
  diabetes mellitus
• prolonged vitamin/trace element/amino acid
  deficiency (starvation, malnutrition)
• medicines, alcohol, toxins (aflatoxin, Bacillus
  cereus toxin)), organic solvents
• viruses (Hepatitis B,C, HIV), bacteria, parasites
• cholostasis
• tumor

• Normal functions of liver
• uptake and degradation of glucose, galactose,
  fructose to yield energy
• formation and degradation of glycogen to maintain
  blood sugar level
• synthesis and secretion of glucose from taken up
  lactate, glycerol, amino acids
• synthesis of aminosugars, glycoproteins,
  secretion of some blood proteins

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• synthesis of glucuronic acid, conjugation of
  endogenious and exogenious molecules with it to
  be excreted
• uptake and degradation of lipoprotein remnants
• uptake of fatty acids, glycerol, cholesterol
  ester from lipoproteins
• synthesis and degradation of fatty acids (any
  kind), TAG, phospholipids
• storage of some TAG, and cholesterol ester
• synthesis of cholesterol, its ester, bile acids,
  utake of bile acids
• formation and secretion of VLDLand nascent HDL to
  blood
• formation and secretion of bile to gall bladder
  (than to duodenum)
• uptake and degradation of free fatty acids
  derived from adipocytes, formation and secretion
  of ketone bodies to blood
• storage of some vitamins, metals, blood
• synthesis of hemostasis proteins, IGF
• uptake and degradation, detoxification of all
  kind of hormons
• uptake and degradation of old proteins from blood

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Alcoholic liver failure Alcohol can cause
hepatitis, steatosis, steatohepatitis, cirrhosis,
carcinoma. steatosis occures because the high
amount of NADH (produced by alcohol
dehydrogenase) shifts reactions toward
formation of glycerol-3-P oxigen free radicals
deteorate mitochondrial enzymes including
respiratory chain and beta-oxidation, so FAs
can not be broken down inflammation caused by ROS
from respiratory chain and CYP (cytochrome
P450), by TNFa, IL-8, TGF-beta from
macrophages fibrosis and further cirrhosis is
caused by TNFa, TGF-beta, IL-6, (leptin in
obese) necrosis and apoptosis patomechanism
contains ROS, mutated DNA, aldehyde- protein
adduct considered as foreign and immunogenic,
enzymes inactivation by ROS, decrease of
protecting antioxidant molecules GSH, vitmin C
and E, antioxidant enzymes
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• Signs of chronic liver failure and reasons of the
  signs
• albumin synthesis ?? colloid osmotic pressure ??
  edema
• synthesis of hemostasis proteins ?? bleeding and
  thrombosis at the same time
• biotransformation ?? bilirubin conjugation ??
  icterus jaundice transformation and excretion
  of androgens is faster than estrogens
  ? feminization of men testis atrophy,
  gynecomastia
• abnormal amino acid degradation fetor hepaticus
  special smell
• hyperammonemia ? hepatic encephalopathy stages
• slowness of mentation, disturbed
  sleep drowsiness, inappropriate
  behavior confusion, dysorientation,
  agiteted coma (not respond to any stimuly)

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• Treatment
• elimination of the injureous something
• supply of antioxidant trace elements, amino
  acids, vitamins selen, zink, manganeese,
  vitamin C,E
• proper nutrition (cease of starvation or
  malnutrition)
• withrawal or low dose of medicines
• no immunsuppressants or steroids
• Steatosis and fibrosis are reversible. Cirrhosis
  is uncurable. Carcinoma can be eliminated by
  surgery.

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6.) tumor, cirrhosis, thrombosis ? portal
hypertension ? a.) portocaval shunts (blood
vessel collaterals that bypass th liver from
gut to systemic veins) b.) ascites (fluid in
abdomen) c.) hepatorenal syndrome (anuria) d.)
esophagus rupture and bleeding
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• How serious is the liver failure depends on
• genetic polymorphism effectiveness or
  susceptibility of proteins
• additive and synergistic effect of environment
  alcohol medicine viral infection fungi
  toxin is more serious than separately
• food every overfeeding oxidative
  stress starvation, malnutrion leads to amino
  acid, trace element, or vitamin deficiency
  that sensitizes the liver to next insult
• male or female lipid protein ratio and
  localization is different sexual steroids effect
  on metabolism differently
• increases with age radiation, chemical agents
  etc. cause mutations, their correction is
  detiorated
• the illness of other organs can be a reason and
  consequence as well