Hepatic Faiure分析课件
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disturbance of ornithine circle ↓
diminished removal of ammonia by urea synthesis.
15
2) Excessive generation of ammonia
① Liver cirrhosis and portal vein hypertension → decreased bile secretion, blood stagnancy and edema of enteric wall → dysfunction of digestion and absorption bacteria propagation → increased generation of ammonia;
(2) bOiblestsaecclreeotef bainled seexccrreetteea: nd excrete: hyperbilirubinemia, intrahepatic cholestasis
(3) cDoiasgourdlaertioofnc: oagulation: generation↓ or consumption↑ → clotting factor↓→ bleeding tendency
5
Section 2. Hepatic Encephalopathy
6
A. Concept and classification
Acute or chronic liver disease
A serial of Neuropsychical symptoms hepatic encephalopathy
l ) Reversibility of symptoms 2) Dissemination of disease region 3) No clear evidence of morphologic alteration 4) Accompanied with biochemical abnormality
11
Evidences supporting ammonia intoxication ①The ammonia level in blood or CSF of patient with HE was
increased by 1~3 fold. ② HE may be induced by eating nitrogen-containing food in
→ATP generation↓
acid
acetyl COA Choline Acetylcholine
Succinic
acid ATP Citric acid
a-Ketoglutaric acid
①Excessive consumption of a- ketoglutaric acid
severe disturbance of liver function in metabolism, secretion, synthesis, detoxication and immunity
↓ jaundice, bleeding, infection, renal dysfunction and
9
Several hypotheses of the pathogenesis of HE have been proposed:
Theory of ammonia intoxication False neurotransmitter hypothesis Theory of amino acid imbalance Theory of GABA(gamma-aminobutyric acid)
Besides, decreased H+ in renal tubule caused by respiratory alkalosis or carbonic anhydrase inhibiter may increase NH3 diffuse from kidney into blood. Elevation of pH in bowel lumen may increase absorption of NH3 into blood.
g-aminobutyric acid
→ hindering tricarboxylic
acid cycle
Glutamic
glutamine
acid
ATP
④KrEexbcessscivietrciocnsaucmipdtiocnyocflAeTP by synthesis of glutamine
(4) bDiyoscfounnvcetirosnioonf bioconversion drug metabolism; detoxication of toxin; inactivation of hormone
(5) iDmymsfuncetion of immune (Kuppfer cells) bacterial infection, bacteremia, intestinal endotoxemia
encephalopathy ↓
“Hepatic insufficiency” ↓
(late stage) “Hepatic failure” hepatorenal syndrome and hepatic encephalopathy
3
2. Classification and causes
Severe, extensive degeneration and necrosis of hepatic cells → Acute (fulminant) hepatic failure
None of them is necessarily exclusive. A conservative and conventional view of HE is
Almost certainly the etiology is multifactorial
10
1. Theory of ammonia intoxication
8
B. Pathogenesis of HE
HE is a neuropsychical disturbance. The following features may imply HE is mainly caused by the metabolic and functional disturbance of the brain:
Glycose Glucose-6-phosphate
② Excessive consumption
NH
reduced coenzyme I → hindering delivery ofLaHc+tic acid
3
Pyruvic acid
in respiratory chain
Oxaloacetic
Late stage of cirrhosis or carcinoma of the liver → Chronic hepatic failure
4
3. FEuffnectisoonfohfenpoartimc afal illiuvreer on the body
(1) mDiesttaubrboalniscme :of metabolism: carbohydrate, protein, electrolyte
18
l ) Interfering cerebral energy metabolism
③Inhibiting activity of pyruvic acid decarboxylase → generation of acetyl coenzyme A↓ →impairing TA cycle
② Accompanied bleeding of alimentary tract;
16
③ Accompanied renal dysfunction → urea excretion↓, urea diffusion into intestine↑
④ jactitation, tremor → muscle motion↑ → ammonia generation by catabolism of adenosine.
17
(2) Toxic role of ammonia on brain
l ) Interfering cerebral energy metabolism. 2) Changing neurotransmitter in the brain 3) Direct inhibitory effect on neural cell membrane
Hepatic coma ultimate clinical manifestation of HE
7
Classification:
According to the Clinic course Acute, subacute and chronic types Clinical neuropsychical symptoms 1st stage (prodromal period) 2nd stage (pre-coma period) 3rd stage (lethargy period) 4th stage (coma period) Etiology Virus infection or drug intoxication → extensive hepatocyte necrosis → acute (fulminant) hepatitis → endogenous HE Portal or Schistosome hepatic cirrhosis → exogenous HE ( usually with obvious inducing factors)
Ammonia is wildly believed to play a role in the pathogenesis of HE.
However, a precise role for ammonia in the pathogens of HE has yet to be clearly defined.
12
The metabolism of ammonia
citrulline
ATP
Enzymes
urea 2 25%
1
13
(1) Causes of increased plasma level of ammonia
l ) Decreased urea synthesis and inadequate removal of ammonia
patients with liver cirrhosis, and restricting intake may alleviate HE. ③ Ammonia-lowering treatment was effective in part of patients with HE. ④ Animal model of HE may created with ammonium chloride.
Chapter 17． Hepatic Failure
1
Section 1. Concept of hepatic failure
2Байду номын сангаас
1. Definition of hepatic failure
Various harmful factors ↓
parenchymal cells and Kupffer cells damadged severely and extensively ↓
2) Excessive generation of ammonia
14
l ) Decreased urea synthesis inadequate removal of NH3
Severe damaged of liver ↓
dysfunction of enzyme system, inadequate substrate and lack of ATP ↓
diminished removal of ammonia by urea synthesis.
15
2) Excessive generation of ammonia
① Liver cirrhosis and portal vein hypertension → decreased bile secretion, blood stagnancy and edema of enteric wall → dysfunction of digestion and absorption bacteria propagation → increased generation of ammonia;
(2) bOiblestsaecclreeotef bainled seexccrreetteea: nd excrete: hyperbilirubinemia, intrahepatic cholestasis
(3) cDoiasgourdlaertioofnc: oagulation: generation↓ or consumption↑ → clotting factor↓→ bleeding tendency
5
Section 2. Hepatic Encephalopathy
6
A. Concept and classification
Acute or chronic liver disease
A serial of Neuropsychical symptoms hepatic encephalopathy
l ) Reversibility of symptoms 2) Dissemination of disease region 3) No clear evidence of morphologic alteration 4) Accompanied with biochemical abnormality
11
Evidences supporting ammonia intoxication ①The ammonia level in blood or CSF of patient with HE was
increased by 1~3 fold. ② HE may be induced by eating nitrogen-containing food in
→ATP generation↓
acid
acetyl COA Choline Acetylcholine
Succinic
acid ATP Citric acid
a-Ketoglutaric acid
①Excessive consumption of a- ketoglutaric acid
severe disturbance of liver function in metabolism, secretion, synthesis, detoxication and immunity
↓ jaundice, bleeding, infection, renal dysfunction and
9
Several hypotheses of the pathogenesis of HE have been proposed:
Theory of ammonia intoxication False neurotransmitter hypothesis Theory of amino acid imbalance Theory of GABA(gamma-aminobutyric acid)
Besides, decreased H+ in renal tubule caused by respiratory alkalosis or carbonic anhydrase inhibiter may increase NH3 diffuse from kidney into blood. Elevation of pH in bowel lumen may increase absorption of NH3 into blood.
g-aminobutyric acid
→ hindering tricarboxylic
acid cycle
Glutamic
glutamine
acid
ATP
④KrEexbcessscivietrciocnsaucmipdtiocnyocflAeTP by synthesis of glutamine
(4) bDiyoscfounnvcetirosnioonf bioconversion drug metabolism; detoxication of toxin; inactivation of hormone
(5) iDmymsfuncetion of immune (Kuppfer cells) bacterial infection, bacteremia, intestinal endotoxemia
encephalopathy ↓
“Hepatic insufficiency” ↓
(late stage) “Hepatic failure” hepatorenal syndrome and hepatic encephalopathy
3
2. Classification and causes
Severe, extensive degeneration and necrosis of hepatic cells → Acute (fulminant) hepatic failure
None of them is necessarily exclusive. A conservative and conventional view of HE is
Almost certainly the etiology is multifactorial
10
1. Theory of ammonia intoxication
8
B. Pathogenesis of HE
HE is a neuropsychical disturbance. The following features may imply HE is mainly caused by the metabolic and functional disturbance of the brain:
Glycose Glucose-6-phosphate
② Excessive consumption
NH
reduced coenzyme I → hindering delivery ofLaHc+tic acid
3
Pyruvic acid
in respiratory chain
Oxaloacetic
Late stage of cirrhosis or carcinoma of the liver → Chronic hepatic failure
4
3. FEuffnectisoonfohfenpoartimc afal illiuvreer on the body
(1) mDiesttaubrboalniscme :of metabolism: carbohydrate, protein, electrolyte
18
l ) Interfering cerebral energy metabolism
③Inhibiting activity of pyruvic acid decarboxylase → generation of acetyl coenzyme A↓ →impairing TA cycle
② Accompanied bleeding of alimentary tract;
16
③ Accompanied renal dysfunction → urea excretion↓, urea diffusion into intestine↑
④ jactitation, tremor → muscle motion↑ → ammonia generation by catabolism of adenosine.
17
(2) Toxic role of ammonia on brain
l ) Interfering cerebral energy metabolism. 2) Changing neurotransmitter in the brain 3) Direct inhibitory effect on neural cell membrane
Hepatic coma ultimate clinical manifestation of HE
7
Classification:
According to the Clinic course Acute, subacute and chronic types Clinical neuropsychical symptoms 1st stage (prodromal period) 2nd stage (pre-coma period) 3rd stage (lethargy period) 4th stage (coma period) Etiology Virus infection or drug intoxication → extensive hepatocyte necrosis → acute (fulminant) hepatitis → endogenous HE Portal or Schistosome hepatic cirrhosis → exogenous HE ( usually with obvious inducing factors)
Ammonia is wildly believed to play a role in the pathogenesis of HE.
However, a precise role for ammonia in the pathogens of HE has yet to be clearly defined.
12
The metabolism of ammonia
citrulline
ATP
Enzymes
urea 2 25%
1
13
(1) Causes of increased plasma level of ammonia
l ) Decreased urea synthesis and inadequate removal of ammonia
patients with liver cirrhosis, and restricting intake may alleviate HE. ③ Ammonia-lowering treatment was effective in part of patients with HE. ④ Animal model of HE may created with ammonium chloride.
Chapter 17． Hepatic Failure
1
Section 1. Concept of hepatic failure
2Байду номын сангаас
1. Definition of hepatic failure
Various harmful factors ↓
parenchymal cells and Kupffer cells damadged severely and extensively ↓
2) Excessive generation of ammonia
14
l ) Decreased urea synthesis inadequate removal of NH3
Severe damaged of liver ↓
dysfunction of enzyme system, inadequate substrate and lack of ATP ↓