Liver Intro and Dse

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LIVER AND LIVER FUNCTION TESTMa. Dara Mae M. Velasco


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GROSS ANATOMY

liver is a large and complex organ weighingapproximately 1.21.5 kg in the healthy adult. Itis located beneath and is attached to thediaphragm

It is divided unequally into two lobes by the

falciform ligament, with the right lobe beingapproximately six times larger than the left lobe.


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GROSS ANATOMY - blood supply from two sources:

a. the hepatic artery - branch of the aorta, supplies oxygen-rich blood

from the heart to the liver and is responsible forproviding approximately 25% of the total bloodsupply to the liver.

b. the portal vein - portal vein supplies nutrient-rich blood from the

digestive tract, and it is responsible for providingapproximately 75% of the total blood supply to the

liver. - Approximately 1,500 mL of blood passes throughthe liver per minute.

- The liver is drained by a collecting system of veinsthat empties into the hepatic veins and ultimately

into the inferior vena cava


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MICROSCOPIC ANATOMY

Two major cell types:A. hepatocytes making up approximately 80% of the volume of the

organ, are large cells that radiate outward from thecentral vein in plates to the periphery of thelobule.These cells perform the major functionsassociated with the liver and are responsible for theregenerative properties of the liver

B. kupffer cells

macrophages that line the sinusoids of the liver andact as active phagocytes capable of engulfing bacteria,debris, toxins, and other substances flowing throughthe sinusoids


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Excretory and Secretory

One of the most important functions of the liver

substances into the bile or urine such as themajor heme waste product,bilirubin.

Bile is made up of bile acids or salts, bilepigments, cholesterol, and other substances

extracted from the blood body produces approximately 3 L of bile per day

and excretes 1 L of what is produced


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Formation of bile

1. RBCs are phagocytized in the spleen. Hemoglobin is catabolized into

globin, iron and heme.2. Heme ring is broken open and converted to unconjugated ( indirect

) bilirubin.

3. RE cells in the spleen secrete unconjugated bilirubin into the plasma,where bilirubin is bound byalbumin.

4. Albumin bilirubin complex travels to the liver.5. Hepatocytes conjugates bilirubin with gluconic acid and UDPGT

enzyme.

6. Conjugated bilirubin secreted into the bile ducts ( GI tract )

7. GI bacterial normal flora convert conjugated bilirubin into

urobilinogen.

8. Urobilinogen may be excreted into the stool, reabsorbed into the plasmaand excreted in the urine


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Synthetic

The liver has extensive synthetic capacity

carbohydrates, lipids, and proteins


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Synthetic

metabolism of carbohydrates is one of the mostimportant functions of the liver.

(1) use the glucose for its own cellular energyrequirements,

(2) circulate the glucose for use at the peripheraltissues,

(3) store glucose as glycogen (principal storage form ofglucose) within the liver itself or within other tissues.


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Synthetic

Lipids are synthesized in the liver under normalcircumstances

The liver gathers free fatty acids from the diet, andthose produced by the liver itself, and breaking them

down to produce acetyl-CoA. Acetyl-CoA can then enter several pathways to form

triglycerides, phospholipids, or cholesterol.

The liver is also involved in the metabolism of lipidsand their removal from the body through the use oflipoproteins and apoproteins


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Synthetic

Almost all proteins are synthesized by the liver exceptfor the immunoglobulins and adult hemoglobin

positive and negative acute-phase reactants andcoagulation proteins

also serves to store a pool of amino acids throughprotein degradation


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Detoxification and Drug Metabolism

gatekeeper between substances absorbed by thegastrointestinal tract and those released intosystemic circulation

Every substance that is absorbed in thegastrointestinal tract must first pass through theliver; this is referred to asfirst pass

It may either bind the material reversibly so as

to inactivate the compound, or it may chemicallymodify the compound so it can be excreted most important mechanism is the drug-

metabolizing system of the liver (cytochrome P-

450 isoenzymes)


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LIVER FUNCTION ALTERATIONS

DURING DISEASE Jaundice (icterus)- French wordjaune,which means yellow, Jaundice, or is used to describe the yellow discoloration of the

skin, eyes, and mucous membranes most oftenresulting from the retention of bilirubin; however, itmay also occur due to the retention of othersubstances

jaundice is usually not noticeable to the naked eye

until bilirubin levels reach 3.0 mg/dL icterus is most commonly used in the clinicallaboratory to refer to a serum or plasma sample witha yellow discoloration due to an elevated bilirubinlevel


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LIVER FUNCTION ALTERATIONS

DURING DISEASE Reference ranges

Total Bilirubin ( conjugated + unconjugated )0.2 - 1.0 mg / dl

Conjugated bilirubin 0.0 - 0.2 mg / dl

Fullterm newborns 2.0 6.0 mg / dl

Jaundice is evident at 3.0 mg / dl


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General classifications of jaundice

Prehepatic Hepatic Posthepatic


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Prehepatic Before it reaches the liver metabolism

Excess RBC destruction ( Not impaired liver function )

Increased unconjugated bilirubin


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Hepatic intrinsic liver defect or disease can be due to

disorders of bilirubin metabolism and transportdefects, due to diseases resulting in

hepatocellular injury or destruction Gilbert disease, Crigler-Najjar syndrome, andphysiologic jaundice of the newborn are hepaticcauses of jaundice that result in elevations in

unconjugated bilirubin Dubin-Johnson and Rotor syndrome are hepatic

causes of jaundice that result in elevations inconjugated bilirubin.


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Gilberts Syndrome

Defective bilirubin transport intohepatocyte Most common cause of jaundice Relatively benign intermittent unconjugated

hyperbilirubinemia in the absence ofhemolysis and underlying liver

disease UGT (uridine diphosphoglucoseglucuronyltransferase) superfamily


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Crigler Najjar Syndrome

chronic nonhemolytic unconjugated hyperbilirubinemia Rare and more serious disorder of bilirubin metabolism resulting from a

molecular defect within the gene involved with bilirubin

conjugation UDPG deficiency Hepatocytes lack UDPG enzyme cannot conjugate

bilirubin

type 1 - complete absence of enzymatic bilirubinconjugation

type II mutation causing a severe deficiency of theenzyme responsible for bilirubin conjugation


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Dubin Johnson

rare inherited disorder caused by a deficiencyof the canalicular multidrug resistance/multispecific organic anionic transporterprotein Defective excretion of conjugated bilirubin leading to hyperbilirubinemia andbilirubinuria Dubin-Johnson is a condition that is

obstructive in nature, so much of theconjugated bilirubin circulates bound toalbumin

distinguishing feature is the appearance of dark-stainedgranules on a liver biopsy sample.


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Rotors Syndrome

Defective secretion of conjugated bilirubin clinically similar to Dubin-Johnson syndrome but the

defect causing Rotor syndrome is not known

due to a reduction in the concentration or activity ofintracellular binding proteins such as ligandin.

liver biopsy does not show dark pigmented granules


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Physiological Jaundice of the newborn

Immature liver at birth Temporary deficiency of UDPG Small / moderate elevated unconjugated bilirubin

lasting a few days


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Posthepatic Impaired ability of liver to excrete bile into the GI tract (

gallstones, tumors )

prevent the flow of conjugated bilirubin into thebile canaliculi

stool loses its source of normal pigmentationand becomes clay-colored.


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Cirrhosis

scar tissue replaces normal, healthy liver tissue blockingthe flow of blood through the organ and prevents theliver from functioning properly

signs and symptoms appear, including fatigue, nausea,unintended weight loss, jaundice, bleeding from thegastrointestinal tract, intense itching, and swelling in thelegs and abdomen

cause of cirrhosis is chronic alcoholism and chronichepatitis C virus infection. Chronic hepatitis B and Dvirus infection, autoimmune hepatitis, inheriteddisorders (e.g., 1-antitrypsin deficiency, Wilson disease,

hemachromatosis, and galactosemia), nonalcoholicsteatohepatitis, blocked bile ducts, drugs, toxins, andinfections

Liver damage from cirrhosis cannot easily be reversed,but treatment can stop or delay further progression of

the disorder


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Tumors

May also be classified as :

a. Benign - include hepatocellular adenoma (rarecondition occurring almost exclusively infemales of child-bearing age) and hemangiomas(masses of atypical blood vessels usuallymesenchymal in origin with no known etiology

b. Malignant - Malignant tumors of the liverinclude hepatocellular carcinoma (HCC),hepatocarcinoma, and hepatoma


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Tumors

Classified as

1. Primary begins in the liver cells

2. Metastatic -occurs when tumors from otherparts of the body spread (metastasize) to theliver. This type is more common.

Cancers that commonly spread to the liver

include colon, lung, and breast cancer May also be classified as :

a. Benign -

b. Malignant


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Reye Syndrome

group of disorders caused by infectious, metabolic,toxic, or drug induced disease found almostexclusively in children

often preceded by a viral syndrome such as varicella,

gastroenteritis, or an upper respiratory tractinfection such as influenza Ingestion of aspirin the course of the viral infection acute illness characterized by noninflammatory

encephalopathy and fatty degeneration of the liverwith a clinical presentation of profuse vomitingaccompanied with varying degrees of neurologicimpairment such as fluctuating personality changesand deterioration in consciousness


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Drug- and Alcohol-Related Disorders

Acute liver failure liver is a primary target organ for adverse drug

reactions because it plays a central role in drugmetabolism

Toxicity via immune-mediated injury to thehepatocytes

most important is ethanol

ethanol causes very mild, transient, andunnoticed injury to the liver; however,

with heavier and prolonged consumption,it can lead to alcoholic cirrhosis


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The elimination of alcohol requires the enzymesalcohol dehydrogenase and acetaldehydedehydrogenase to convert alcohol toacetaldehyde and subsequently to acetate. The

acetate can then be oxidized to water and carbondioxide, or it may enter the citric acid cycle. liver abnormalities that may range from

alcoholic fatty liver with inflammation

(steatohepatitis) to scar tissue formation,as in hepatic fibrosis, to the destructionof normal liver structure seen in hepaticcirrhosis.


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This type of liver injury may be categorized intothree stages:

a. alcoholic fatty liver - represents the mildestcategory

characterized by slight elevations in AST, ALT,and GGT, and on biopsy, fatty infiltrates arenoted in the vacuoles of the liver.

tends to affect young to middle-aged people witha history of moderate alcohol consumption. Acomplete recovery within 1 month is seen whenthe drug is removed.


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This type of liver injury may be categorized intothree stages:

a. alcoholic hepatitis

moderately elevated AST, ALT, GGT, and ALPand elevations in total bilirubin up to 30 mg/dL.

Serum proteins, especially albumin, aredecreased and the prothrombin time is

prolonged. Prognosis is dependent on the type and severity

of damage to the liver

alcoholic cirrhosis


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This type of liver injury may be categorized intothree stages:c. alcoholic cirrhosis Prognosis associated with alcoholic cirrhosis is

dependent on the nature and severity of associated

conditions such as a gastrointestinal bleeding or ascitis the 5-year survival rate is 60% in those who abstainfrom alcohol and 30% in those who continue to drink.

This condition appears to be more common in malesthan in female

Laboratory abnormalities include increased liverfunction tests (AST, ALT, GGT, ALP, total bilirubin),decreased albumin, and a prolonged prothrombin time.

A liver biopsy if the only method by which a definitivediagnosis may be made


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LECTURE 2

Liver Intro and Dse

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