Transcript Signs of acut liver failure

ACUT AND CHRONIC LIVER
FAILURE
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%)
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,B+D, E,F,G, Cytomegalov., Varicella zoster,
Adenov., Eppstein-Barr v., Q-fever, Yellow-fever
systemic: sepsis...
metabolic
Among all the acut liver failure phenacetin/paracetamol=acetaminophen 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
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)
Reasons of chronic liver failure
1) overfeeding, obesity, insulin resistance, diabetes mellitus
2) prolonged vitamin/trace element/amino acid deficiency (starvation, malnutrition)
3) medicines, alcohol, toxins (aflatoxin, Bacillus cereus toxin)), organic solvents
4) viruses (Hepatitis B,C, HIV), bacteria, parasites
5) cholostasis
6) tumor
Normal functions of liver
a) uptake and degradation of glucose, galactose, fructose to yield energy
b) formation and degradation of glycogen to maintain blood sugar level
c) synthesis and secretion of glucose from taken up lactate, glycerol, amino acids
d) synthesis of aminosugars, glycoproteins, secretion of some blood proteins
e) synthesis of glucuronic acid, conjugation of endogenious and exogenious
molecules with it to be excreted
f) uptake and degradation of lipoprotein remnants
g) uptake of fatty acids, glycerol, cholesterol ester from lipoproteins
h) synthesis and degradation of fatty acids (any kind), TAG, phospholipids
i) storage of some TAG, and cholesterol ester
j) synthesis of cholesterol, its ester, bile acids, utake of bile acids
k) formation and secretion of VLDLand nascent HDL to blood
l) formation and secretion of bile to gall bladder (than to duodenum)
m) uptake and degradation of free fatty acids derived from adipocytes, formation and
secretion of ketone bodies to blood
n) storage of some vitamins, metals, blood
o) synthesis of hemostasis proteins, IGF
p) uptake and degradation, detoxification of all kind of hormons
q) uptake and degradation of old proteins from blood
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, aldehydeprotein adduct considered as foreign and immunogenic, enzymes’
inactivation by ROS, decrease of protecting antioxidant molecules:
GSH, vitmin C and E, antioxidant enzymes
Signs of chronic liver failure and reasons of the signs
1) albumin synthesis ↓→ colloid osmotic pressure ↓→ edema
2) synthesis of hemostasis proteins ↓→ bleeding and thrombosis at the same time
3) biotransformation ↓→
bilirubin conjugation ↓→ icterus = jaundice
transformation and excretion of androgens is faster than estrogens →
feminization of men: testis atrophy, gynecomastia
4) abnormal amino acid degradation: fetor hepaticus = special smell
5) hyperammonemia → hepatic encephalopathy stages:
slowness of mentation, disturbed sleep
drowsiness, inappropriate behavior
confusion, dysorientation, agiteted
coma (not respond to any stimuly)
Treatment
a) elimination of the injureous something
b) supply of antioxidant trace elements, amino acids, vitamins: selen, zink,
manganeese, vitamin C,E
c) proper nutrition (cease of starvation or malnutrition)
d) withrawal or low dose of medicines
e) no immunsuppressants or steroids
Steatosis and fibrosis are reversible. Cirrhosis is uncurable. Carcinoma can be
eliminated by surgery.
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
How serious is the liver failure depends on
a) genetic polymorphism: effectiveness or susceptibility of proteins
b) additive and synergistic effect of environment: alcohol + medicine + viral infection+
fungi toxin is more serious than separately
c) food
every overfeeding = oxidative stress
starvation, malnutrion leads to amino acid, trace element, or vitamin
deficiency that sensitizes the liver to next insult
d) male or female
lipid protein ratio and localization is different
sexual steroids effect on metabolism differently
e) increases with age
radiation, chemical agents etc. cause mutations, their correction is
detiorated
f) the illness of other organs can be a reason and consequence as well