LFT Function

8/9/2019 LFT Function

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Department of Physiology, 3rd

Faculty of Medicine

Liver Function TestsLiver Function Tests


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Faculty of Medicine

LiverLiver

Largest organ in the body

Contributing about 1/50 of the total body weight (about 1.5 kg inadults)

Basic functional unit of the liver is the liverlobule (0.8 -2 mm indiameter; 50-100 thousands in the liver)

High blood flow - 1350 ml/min to liver sinusoids (1050 ml fromthe portal vein, 300 ml from hepatic artery) = functional andnutritive blood circulation

Physiologically low vascular resistance (small difference

between pressures in the portal vein and hepatic vein) - in caseof pathological changes (steatosis or cirrhosis), the vascularresistance increases, blood flow decreases (portalhypertension, ascites)


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Faculty of Medicine

Function of the liverFunction 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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Faculty of Medicine

Function of the liverFunction of the liver (2)(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 itcan 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 cellcontains apoferritin and when excess of iron in the blood it formsferritin) = blood iron buffer

participation on production of erythropoietin


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Faculty of Medicine

FunctionFunction

protein metabolismprotein 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 andsynthesis of other compound from amino acids


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Faculty of Medicine

FunFunctionction

protein metabolism (2)protein metabolism (2)Protein metabolism disorder in hepatic diseases

Ammonia detoxication disorder and failure of urea formation (ammoniacomes from bacterial degradation of nitrogen substances in intestines, fromintestine mucosa during glutamin degradation, from degradation of

aminoacids in kidneys and muscles ) Hyperamonemia = increase of ammonia blood concentration (>50 mol/l)

Hepatic encephalopathy = toxic effect of ammonia in the brain (? Bindingof 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 toxicsubstances bypass the liver through the extrahepatic anastomoses)


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Faculty of Medicine

FunctionFunction

carbohydrate metabolismcarbohydrate metabolism

Maintaining a normal blood glucose concentration

Storage of glycogen (1-4 %) removing excess ofglucose 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 fromintermediate products of carbohydrate metabolism

Pentose phosphate pathway is source of the NADPH(reduction synthesis) and ribose (synthesis ofnucleotides)


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Faculty of Medicine

FunctionFunction

carbohydrate metabolism (2)carbohydrate metabolism (2)Carbohydrate metabolism disorder in hepatic diseases

Hyperglycemia in patients with cirrhosis after carbohydraterich meal (50% has glucose tolerance, 10% has hepatic

diabetes mellitus) Combination of pathological glucose tolerance test, hyperinsulinemia,

and increased insulin tolerance (liver insuficience p decrease ofglucose utilization p hyperglycemia p hyperinsulinemia p down-regulation of insulin receptors p insulin rezistence)

Hypoglycemia in alcohol abusers alcohol suppresses citrate

cycle and thereby impairs gluconeogenesis from aminoacids.After depletion of glycogen storages comes hypoglycemia thatthreatens the patients life.


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Faculty of Medicine

FunctionFunction

fat metabolismfat metabolism

Oxidation of fatty acids to supply energy for other body

function

Synthesis of large quantities of cholesterol (80% ofcholesterol 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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Faculty of Medicine

FunctionFunction

fat metabolism (2)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

ofLCAT (lecitincholesterolacyltransferase) = transformation of VLDL to LDL =cirrhosis

cholesterol decreased esterification of cholesterol when decreased activity ofLCAT

cholesterol decreased excretion of cholesterol in bile due tocholestasis orincreased synthesis due to decreased intestinal resorption of lipids = causessteatosis of the liver

Hepatic steatosis accumulation ofTAG minimaly in of the hepatocytes(if less = steatosis of hepatic cells)

Toxic substances including alcohol and medicaments

Nutrition (obesity, malnutrition, kwashiorkor)

Metabolic disorder(DM, hyperlipoproteinemia, pregnancy)

Inflammation of intestines


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Faculty of Medicine

Composition of bileComposition of bile

Water= 97 %

Bile salts (0.7%) = primary bile acids are transported to the bileas sodium and potassium salts

Cholic acid(converted by colon bacteria to Deoxycholic acid)

Chenodeoxycholic acid(converted by colon bacteria toLithocholic acid)

Function:

reduction of surface tension

responsible for the emulsification of fat preparatory to itsdigestion and absorption in small intestine

tend to form micelles, because of their amphipathic character(have both hydrophilic and hydrophobic domains)


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Faculty of Medicine

Composition of bile (2)Composition of bile (2)

Bile pigment (0,2%) = glucuronides bilirubin andbiliverdin (golden-yellow color of bile)

Cholesterol (0,06%) raises in patients with obstructiveicterus

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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Faculty of Medicine

Enterohepatic circulation of bileEnterohepatic circulation of bile

saltssalts

Micelles = cylindrical discsformed by bile salt

Function: Keeping fat insolution and transporting fatto the brush boarder of theintestinal epithelial cells,

where they are absorbed.Hydrophilic surface and

hydrophobic interior with fatinside (fat acids andcholesterol).

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)


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Faculty of Medicine

Enterohepatic circulation of bileEnterohepatic circulation of bile

salts (2)salts (2) 90-95% of the bile saltare

absorbed from the small intestinesome by nonionic diffusion, mostby Na+ - salt cotransport in the

terminal ileum). 5-10% of the bile saltenter the

colon and are converted todeoxycholic acid (from Cholicacid) or lithocholic acid (fromChenodeoxycholic acid).

Deoxycholic acidis absorbedback and transported back toportal vein of the liver.

Lithocholic acidis insoluble andis mostly excreted.


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Faculty of Medicine

BilirubinBilirubin Metabolism & ExcretionMetabolism & Excretion

Formedin the tissues by the

breakdown of hemoglobin.

In the circulation bound to albumin.

In the liverbilirubin dissociates andfree 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

tercobilinogen and after oxidation to

Stercobilin. Only small amount

escapes into the blood and is excreted

by the urine as Urobilin (oxidized form

ofUrobilinogen).


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Faculty of Medicine

Icterus (Jaundice)Icterus (Jaundice)

Detectable when the total plasma bilirubin > 2mg/dl (34Qmol/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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Faculty of Medicine

Icterus (Icterus (22))

Non-conjugated icterus (hemolytic) due to reasons

1-3 = the free bilirubin rises

Conjugated icterus (obstructive) due to reasons 4or 5 = bilirubin glucuronide regurgitase into the blood

Differentiation

van den Bergh reaction (rate conjugated/non-conjugated

bilirubin in the blood) From urine (non-conjugated bilirubin is not present in urine,

conjugated bilirubin turns urine foam when shaking to

intense yellow)


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Faculty of Medicine

Thanks for your attention!

LFT Function

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