Structure and function of liver and gallbladder

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Structure and function of liver and gallbladder
Romana Šlamberová, M.D. Ph.D.
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Liver

• Largest organ in the body
• Contributing about 1/50 of the total body weight
  (about 1.5 kg in adults)
• Basic functional unit of the liver is the liver
  lobule (0.8 -2 mm in diameter 50-100 thousands
  in the liver)
• High blood flow - 1350 ml/min to liver sinusoids
  (1050 ml from the portal vein, 300 ml from
  hepatic artery) functional and nutritive blood
  circulation
• Physiologically low vascular resistance (small
  difference between pressures in the portal vein
  and hepatic vein) - in case of pathological
  changes (steatosis or cirrhosis), the vascular
  resistance increases, blood flow decreases
  (portal hypertension, ascites)

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Function of the liver

• Liver is the largest gland in the body
• 1. Formation and secretion of bile
• 2. Detoxication of various substances
• Metabolic products of intestine microbes
• Exogenous toxins (medicaments, alcohol, poisons)
• Hormones (thyroxine, estrogen, cortisol,
  aldosterone)
• 3. Synthesis of plasma proteins
• Acute-phase proteins
• Albumin
• Clotting factors
• Steroid-binding and other hormone-binding
  proteins

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Function of the liver (2)

• 4. Coagulation (synthesis of most of the
  coagulating factors).
• Vitamin K is required for the formation of
  Factors II (prothrombin), VII (proconvertin), IX
  (Christmas factor), X (Stuart factor).
• 5. Blood reservoir filtration and storage of
  blood (450 ml almost 10 of the bodys total
  blood volume). In cardiac failure it can be
  stored there up to 1 l of blood.
• 6. Immunity (Kupffer cells macrophages)
• 7. Vitamins - metabolism and storage of vitamins
  A, D and B12
• 8. Relation to blood formation
• storage of vitamin B12
• metabolism of iron and its storage as ferritin
  (hepatic cell contains apoferritin and when
  excess of iron in the blood it forms ferritin)
  blood iron buffer
• participation on production of erythropoietin

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Function protein metabolism

• Deamination of amino acids
• Formation of urea for removal of ammonia from
  the body fluids
• Formation of plasma proteins (90 of all plasma
  proteins, up to 50 g of plasma proteins daily)
  not gamma globulins (cirrhosis very low
  albumins ascites and edema)
• Interconversions of the various amino acids and
  synthesis of other compound from amino acids

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Function protein metabolism (2)

• Protein metabolism disorder in hepatic diseases
• Ammonia detoxication disorder and failure of urea
  formation (ammonia comes from bacterial
  degradation of nitrogen substances in intestines,
  from intestine mucosa during glutamin
  degradation, from degradation of aminoacids in
  kidneys and muscles )
• Hyperamonemia increase of ammonia blood
  concentration (gt50 µmol/l)
• Hepatic encephalopathy toxic effect of ammonia
  in the brain (? Binding of ammonia to glutamate
  glutamine)
• Mental changes (capriciousness, disorientation,
  sleeping disorders, chaotic speech, personality
  changes)
• Motoric changes (increased in muscle reactivity,
  hyperreflexion, tremor)
• Hepatic coma to death
• Endogenous viral hepatitis and poisoning
  (hepatic cells desintegration)
• Exogenous final status of chronic cirrhosis
  (ammonia and other toxic substances bypass the
  liver through the extrahepatic anastomoses)

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Function carbohydrate metabolism

• Maintaining a normal blood glucose concentration
• Storage of glycogen (1-4 ) removing excess of
  glucose from blood, storage, fast return when the
  blood concentration decreases Glucose buffer
  function
• Conversion of galactose and fructose to glucose
• Gluconeogenesis
• Formation of many chemical compounds from
  intermediate products of carbohydrate metabolism
• Pentose phosphate pathway is source of the NADPH
  (reduction synthesis) and ribose (synthesis of
  nucleotides)

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Function carbohydrate metabolism (2)

• Carbohydrate metabolism disorder in hepatic
  diseases
• Hyperglycemia in patients with cirrhosis after
  carbohydrate rich meal (50 has glucose
  tolerance, 10 has hepatic diabetes mellitus)
• Combination of pathological glucose tolerance
  test, hyperinsulinemia, and increased insulin
  tolerance (liver insuficience ? decrease of
  glucose utilization ? hyperglycemia ?
  hyperinsulinemia ? down-regulation of insulin
  receptors ? insulin rezistence)
• Hypoglycemia in alcohol abusers alcohol
  suppresses citrate cycle and thereby impairs
  gluconeogenesis from aminoacids. After depletion
  of glycogen storages comes hypoglycemia that
  threatens the patients life.

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Function fat metabolism

• Oxidation of fatty acids to supply energy for
  other body function
• Synthesis of large quantities of cholesterol (80
  of cholesterol synthesized in the liver is
  converted into bile salts), phospholipids, and
  most lipoproteins
• Inactivation of steroids and their excretion of
  the body
• Synthesis of fat from proteins and carbohydrates

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Function fat metabolism (2)

• Fat metabolism disorder in hepatic diseases
• Dyslipoproteinemia
• Hypertriacylglycerolemia - ? LDL from decreased
  activity of hepatic lipase
• ? IDL (intermediate density lipoprotein) and ?
  HDL from decreased production of LCAT
  (lecitincholesterolacyltransferase)
  transformation of VLDL to LDL cirrhosis
• ? cholesterol decreased esterification of
  cholesterol when decreased activity of LCAT
• ? cholesterol decreased excretion of
  cholesterol in bile due to cholestasis or
  increased synthesis due to decreased intestinal
  resorption of lipids causes steatosis of the
  liver
• Hepatic steatosis accumulation of TAG minimaly
  in ½ of the hepatocytes (if less steatosis of
  hepatic cells)
• Toxic substances including alcohol and
  medicaments
• Nutrition (obesity, malnutrition, kwashiorkor)
• Metabolic disorder (DM, hyperlipoproteinemia,
  pregnancyí)
• Inflammation of intestines

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Amount of abused alcohol and its level in the
blood
 
Drunk up at once on an empty stomach 0,4 in
blood
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Acute intoxication with alcohol
Stage 1 Signs of drunkenness are not necessary
evident Basic symptom is euphoria. Patient is
talkative or in contrast silent more than
usually and has subjective feeling of increased
mental activity. Objectively decreased reflex
reactions and working performance Stage 2
Selfcontrol disorders Inattention and talking
problems Unsteady walking Increased
self-confident Loss of emotions control
increased aggressiveness or tearfulness
Increased libido, decreased capability.
Decreased reflex reaction Dangerous for car
driving!
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Acute intoxication with alcohol (2)

• Stage 3 High muzziness
• Unsteady walking or unable to walk
• Unclear talking
• Often nausea and vomiting
• Falling a sleep
• Stage 4 Deep sleep followed by coma
• Cold skin
• Bradypnoa a tachycardia
• Coma
• Death due to failure of breeding and vasomotor
  centers.

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Bile

• secreted by cells of the liver into the bile
  duct, which drains into the duodenum.
• Between meals the duodenal orifice (m. sfincter
  Oddi) is closed and bile flows into the
  gallbladder, where it is stored (50 80 ml).
• The bile is concentrated in the gallbladder from
  97 to 89 of the water (osmotic gradient)
• m. sfincter Oddi opens by food intake within 30
  minutes, the presence of aminoacids and fatty
  acids in duodenum activates the cholecystokinin,
  which causes gallbladder contractions and
  excretion of bile
• production of 500-1000 ml of bile daily
• pH 7,1-7,3

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Composition of bile

• Water 97
• Bile salts (0.7) primary bile acids are
  transported to the bile as sodium and potassium
  salts
• Cholic acid (converted by colon bacteria to
  Deoxycholic acid)
• Chenodeoxycholic acid (converted by colon
  bacteria to Lithocholic acid)
• Function
• reduction of surface tension
• responsible for the emulsification of fat
  preparatory to its digestion and absorption in
  small intestine
• tend to form micelles, because of their
  amphipathic character (have both hydrophilic and
  hydrophobic domains)

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Composition of bile (2)

• Bile pigment (0,2) glucuronides bilirubin and
  biliverdin (golden-yellow color of bile)
• Cholesterol (0,06) raises in patients with
  obstructive icterus
• Inorganic salts (0,7)
• Fatty acids (0,15)
• Lecithin (0,1) the main phospholipide of bile
• Fat (0,01)
• Alcaline phosphatase

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Enterohepatic circulation of bile salts
Daily synthesis of bile salt to replaced the
lost 0.2 0.4 g/day The total bile salt pool
3.5 g Recycling the entire pool recycles 6-8
times / day (2 times / meal)

• Micelles cylindrical discs formed by bile salt
• Function Keeping fat in solution and
  transporting fat to the brush boarder of the
  intestinal epithelial cells, where they are
  absorbed.
• Hydrophilic surface and hydrophobic interior with
  fat inside (fat acids and cholesterol).

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Enterohepatic circulation of bile salts (2)

• 90-95 of the bile salt are absorbed from the
  small intestine some by nonionic diffusion, most
  by Na - salt cotransport in the terminal ileum).
• 5-10 of the bile salt enter the colon and are
  converted to deoxycholic acid (from Cholic acid)
  or lithocholic acid (from Chenodeoxycholic acid).
  
• Deoxycholic acid is absorbed back and transported
  back to portal vein of the liver.
• Lithocholic acid is insoluble and is mostly
  excreted.

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Bilirubin Metabolism Excretion

• Formed in the tissues by the breakdown of
  hemoglobin.
• In the circulation bound to albumin.
• In the liver bilirubin dissociates and free
  bilirubin enters liver cells, where it is bound
  to cytoplasmic proteins.
• Bilirubin diglucuronide is more water-soluble and
  is mostly transported to the bile canaliculi and
  to the intestines and changes to Stercobilinogen
  and after oxidation to Stercobilin. Only small
  amount escapes into the blood and is excreted by
  the urine as Urobilin (oxidized form of
  Urobilinogen).

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Icterus (Jaundice)

• Detectable when the total plasma bilirubin gt
  2mg/dl (34 ?mol/l)
• Reasons
• excess production of bilirubin (hameolytic
  anemia)
• decreased uptake of bilirubin into hepatic cells
• disturbed intracellular protein binding or
  conjugation
• disturbed secretion of conjugated bilirubin into
  the bile canaliculi
• intrahepatic or extrahepatic bile duct
  obstruction

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Icterus (2)

• Non-conjugated icterus (hemolytic) due to reasons
  1-3 the free bilirubin rises
• Conjugated icterus (obstructive) due to reasons 4
  or 5 bilirubin glucuronide regurgitase into the
  blood
• Differentiation
• van den Bergh reaction (rate conjugated/non-conjug
  ated bilirubin in the blood)
• From urine (non-conjugated bilirubin is not
  present in urine, conjugated bilirubin turns
  urine foam when shaking to intense yellow)