Liver Disease - Russian State Medical...
Transcript of Liver Disease - Russian State Medical...
Liver Disease
Lecture by Bogush N.L.
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Types of liver disease
• Acute or chronic
• Focal or diffuse
• Mild or severe
• Reversible or irreversible
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3 Structure of the liver lobule
Hepatic bar or plate
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nucleus
Space of Disse
Kupffer cell
Glycogen
granules
canaliculus
Hepatic cell
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Liver functions
• A. Excretory function (bile) + role in the
pigment metabolism
• B. Metabolic + detoxificating functions
• C. Barrier function
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A. Pigment metabolism.
RBC Spleen Heme
Senescent +
myoglobin,
catalase,cyto-
chromes
UCB albumin (H2O-insoluble)
LIVER
Splenic, portal veins
CB
bile
urobilinogen
stercobilinogen
Feces - stercobilin (color)
b
a
ct
er
ia
Hemorr.
veins
v.cava inf
kidney
Urine
stercobilin
Intestinal tract
blood
UCB-unconugat-
ed bilirubin
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Bone marrow,
liver
Bile
canaliculus
GT
(GT)
(No GT)
(CB)
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Transformation of bilirubin
Blood UCB albumin
UCB/ albumin
+ glucuronyltransferase
+ glucuronic acids
CB (H2O-soluble)
Smooth
endoplasmatic
reticulum
hepatocyte
Bile canalicules
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Bilirubins in the blood
Total B - 6,8-20,5 mkmol/l
UCB – 75% = 15 mkmol/l
CB – 25% = 5 mkmol/l
Blood bilirubin index – 1/4 - 1/5 (CB:Total B)
Total B > 30-35 mkmol/l ICTERUS:
30-86 – mild
86-170 - moderate
> 171 - severe
CB > 34 mkmol/l bilirubinuria
N
Degree of
severity of
icterus
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Types of Jaundice (Icterus) (from an anatomic standpoint)
• I. Suprahepatic.
• II. Infrahepatic.
• III. Hepatic.
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Bilirubin has a special affinity for elastic tissue (in sclera).
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I. Suprahepatic = hemolytic jaundice
UCB > 35 mkmol/l in blood
icterus (lemon-yellow tint)
CB in bile
urobilinogen
stercobilinogen
in urine in stool UCB>250 mkmol/l
dark urine nuclear (in brain)
icterus encephalopathy No UCB in urine: it is bind +
albumin and H2O-insoluble + anemia= HR,paleness, hypoxia
The gut
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The bile
It contains: bile acids
cholesterol
CB
bicarbonates
lecithin
excretory enzymes:
alkaline phosphatase (AP), 5-nucleotidase, gamma-glutamyl-transpeptidase (GGTP).
micella
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II. Infrahepatic=mechanical jaundice
N UCB in bloodLIVER CB
BILE------ intestinum
into the blood= no bile=
cholemia acholia
stone,
tumor,scar,
cholestasis intestinum
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Cholemia and acholia
BILE X intestinum – no bile!
Bile in blood=cholemia acholia
excretory CB bile acids ADEKF
enzymes CNS heart-vessels: colorless vitamins
icterus asthenia BP, HR feces,
(greenish tint) foaming skin meteorism,
+ urine itching constipation,
dark urine bacterial overgrowth,
(no stercobilin) steatorrhea,creatorrhea
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Cholemia
1)excretory + 2)CB + 3)bile acids
enzymes
icterus skin heart CNS
(greenish tint) -vessels
itching asthenia
dark foaming urine BP
(no stercobilin) HR
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III. Hepatic jaundice
N UB liver (intrahepatic I cholestasis)
UB bile in GUT=
CB = hypo/acholia
Cholemia hepatocellular insufficiency
icterus signs of cytolysis
(ochre color) indicator enzymes (in blood)
AsAT, AlAT,LDG – from cytoplasm,
GDG,MDG – from mitochondrion
+ In blood
Ornitin-carbamiltransferase –
specific liver enzyme Glutamat, malat-
dehydrogenase
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Hepatic pathways
for protein
metabolism and
conversion of
ammonia to urea.
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B. Metabolic function (1)
N disfunction
Proteins.
Synthesis of amino acids in blood
in urine
Synthesis of albumins in blood,
Ponc edemata
Synthesis of
clotting factors hemorrhage syndrome
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Hepatic
pathways
for lipid
metabolism
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B. Metabolic function (2)
N disfunction
Lipids.
Synthesis: of cholesterol ;
of HDLP ;
of bile acids absorption
of lipids in intestinum
+ maldigestion
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Hepatic pathways for glucose metabolism. 27
B. Metabolic function (3)
N disfunction
Carbohydrates.
Synthesis of glucose , hypoglycemia;
Synthesis of glycogen , hypoglycemia.
Depot of vitamins .
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В. Detoxification.
• 1. UB CB
• 2. NH3(from proteins) ornithin circle urea
• 3. Toxins from GIT – phenol, scatol, indole
• 4. Ethyl alcogol aldehyde
• 5. Some medical drugs
• 6. Hormones – aldosteron, ADH, estrogens
(insulin, thyroxin)
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C. Barrier function.
• 1. Cleans the blood from intestinal tract,
spleen, total body.
• 2. Kupffer cells – remove antigens,
immune complexes ( allergy), bacteria and
their toxins.
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Etiology of liver diseases
Primary Secondary
Inborn defects Infections (viruses)
toxins (chemical)
tumors
inflammation
autoimmune disorders
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Pathophysiological syndromes I-XVII
• I. Hepatomegaly.
• II. Hepatosplenic syndrome:
size of the liver and the spleen (they have
common blood and lymphatic outflow,
innervation, system of phagocytes).
• III. Hypersplenism:
Destruction of RBC,L,Planemia, leukopenia,
thrombocytopenia.
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№ IV, V
• IV. Asthenovegetative syndrome:
weakness, fatigue, malaise, depressed mood
bile acids, toxins.
• V. Dyspeptic syndrome:
bad appetite, bitter eructation, flatulence,
constipation intoxication (CNS) +
disorders of digestion in GIT.
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№ VI, VII (1)
• VI. Hemorrhagic syndrome:
1)synthesis of clotting factors in the liver, 2) thrombo-cytopenia, 3) activation of fibrinolytic system.
• VII. Portal hypertension: Phydrostatic in portal vein. Types:
1. Infrahepatic block. 2.Suprahepatic block (right ventricular heart failure). 3.Intrahepatic block (in 70% is caused by cirrhosis of liver).
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№ VII (2)
• Portal hypertension: symptoms and
syndromes:
1. Intoxication (due to blood shunting).
2. Hepatomegaly.
3. Splenomegaly/hepersplenism.
4. Decreased nutrition and body mass.
5. Ascites.
6. Varicosity of the veins.
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№ VII (3)
• Phenomena of shunting.
3 porto-caval shunts:
1. Skin anastomoses (“Medusa head”).
2. In esophagus – can cause a death due to
bleeding from damaged varicose veins.
3. Varicosity of hemorrhoid veins.
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№ VIII
• VIII. Ascites: accumulation of fluid in
the abdominal cavity. Mechanism:
1. Phydrostatic on venous end of capillaries;
2. Poncotic ( albumins);
3. lymph production (from 8-9 l N per day
to 15-20 l), “crying liver”;
4. RAAS + ADH.
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№ IX, X
• IX. Pain syndrome in the right infracostal area: extension of fibrous membrane of the liver, stones in the gall bladder…
• X. Cholestasis: a) partial bile in the intestine. b) dissociated – only CB or only bile acids are retained; c) total cholemia/acholia.
Primary = intrahepatic (cause – in the liver).
Secondary=extrahepatic (cause – in the bile ducts)
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№ XI, XII
• XI. Acholia. No bile acids in the intestine.
active lipase, no emulcification of fat, no
formation of micells (FFA+bile acids),
bicarbonates and pH bad fat digestion and
absorption STEATORRHEA (fat in feces)
+ fat-soluble vit ADEK and F (some FFA) in
organism.
• XII. Cholemia.
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№ XIII, XIV (1)
• XIII. Icterus (with lemon-yellow, orange or green tint).
• XIV. Hepatocellular insufficiency.
1. Carbohydrate metabolism: glycogen store
hypoglycemia, glucuronic acid inadequate detoxication.
2. Protein metabolism: albumins edemata;
dysproteinemia alb/glob, ESR; aminoacids aminoaciduria; urea, ammonium.
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№ XIV (2)
clotting factors I,II,V,IX,X,XIII hemorrhagic
syndrome, blood prothrombin index;
transferrin synthesis + B12 deficiency anemia;
hormonal imbalance aldosteron, estrogenes.
3. Lipid metabolism: chlesterol and bile acids.
4. barrier function of the liver: allergy, toxemia
till a toxic shock.
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№ XV
• XV. Liver failure.
Pathogenetic forms:
1. Excretory (cholestatic); acute
2. Hepatocellular; or
3. Vascular; chronic
4. Combined.
Types: absolute/relative; total/partial; minor/major.
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Acute liver failure. Causes.
• Intoxication with acetaminophen
• Autoimmune hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis C
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Clinical features of acute LF
• Jaundice, icterus + cholestasis
• Encephalopathy
• Coagulopathy
• Portal hypertension (intrahepatic origin) + ascites
and encephalopathy
• Hepatorenal syndrome ( Na retention, water excretion,
renal perfusion, glomerular filtration rate) due to systemic
vasodilation, vasoconstriction of afferent renal arterioles
and renin-angiotensin activity.
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Chronic liver failure. Causes.
• Chronic hepatitis B
• Chronic hepatitis C
• Non-alcoholic fatty liver diseases
• Alcoholic fatty liver diseases
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Clinical features of chronic LF
• Anorexia, weight loss, weakness
• Jaundice, encephalopathy, coagulopathy
• Pruritus (itching)
• Portal hypertension (esophagogastric varices,
splenomegaly + hypersplenism, platelet count)
• Hyperestrogenemia (palmar erythema, spider angiomas
of the skin, hypogonadism and gynecomastia)
• Predisposition to hepatocellular carcinoma
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№ XVI (1)
• XVI. Hepatic coma.
Syndrome developing with absolute, total
( all functions), major (with
encephalopathy) liver failure.
Causes: severe viruses hepatitis, toxic
dystrophy, cirrhosis, portal hypertension…
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№ XVI (2)
The main feature is encephalopathy due to
intoxication.
In blood: cerebrotoxins – ammonium,
phenol, indol, scatol…bile acids…derivates
of pyruvic and lactic acids…FFA…. some
aminoacids…… false neurotransmitters
(octopamine, -phenilethylamine – disturb
synaptic transmission).
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№ XVII
• Extrahepatic symptoms:
pallor (anemia), signs of scratching on the skin (cholemia), xanthomatosis (cholesterol metabolism disorder),
telangiectasias (“vascular spiders”) - pulsating angiomas (0,5-1 sm), palmar erythema (“hepatic palms”), raspberry tongue, gynecomasty estrogens.
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