Liver And Gall Bladder.pdf

LIVER AND GALL BLADDER Dr. Shahida Awais Asst. Prof. Physiology

Physiological Anatomy • Largest organ in the body • 1/50 of total body wt. • Weighs 1.5 kg in avg. adult • Liver Lobule is basic functional unit • Cylindrical 50,000 to 100,000 in human liver • It is hexagonal.

Hepatic Lobule • Blood Supply • Portal vein  portal venules  hepatic sinusoids  central vein • Hepatic artery  hepatic arterioles  hepatic sinusoids  central vein • Central vein  hepatic veins  inferior vena cava

Blood Flow Through The Liver • Pressure in the portal vein ---- about 9 mm Hg • Pressure in the hepatic vein ---- almost exactly 0 mm Hg • Small pressure difference, only 9 mm Hg, shows that the resistance to blood flow through the hepatic sinusoids is normally very low

• 1350 milliliters of blood flows by this route each minute, which is 27% of C.O • 1050 ml from portal vein • 300 ml from hepatic artery

• Cirrhosis of liver greatly increases resistance to blood flow

Liver Cells: Six main types – Hepatocytes – Endothelial cells – Kupffer cells – Perisinusoidal cells – Bile duct cells – Oval cells

Hepatocytes: Parenchymal cell of the liver Polygonal in shape Lacks basement membrane Arranged in single cell plates In the fed state glycogen and lipids are stored in the cytoplasm Iron is stored as ferritin and hemosiderin

Hepatocytes are polarized cells

Lymph Drainage: • The pores in the hepatic sinusoids are very permeable • Allow ready passage of both fluid and proteins into the spaces of Disse • The lymph draining from the liver usually has a protein concentration of about 6 g/dl – only slightly less than the protein concentration of plasma • Large quantities of lymph form – about half of all the lymph formed in the body under resting conditions arises in the liver

FUNCTIONS OF GALLBLADDER • Storage of bile until needed -- Water, Na+, Cl- and other electrolytes are continually absorbed by the mucosa [by active transport of Na+ followed by secondary absorption of Cl-, water and other ions] -- Maximum volume is 30- 60 ml but as much as 450 ml of bile can be stored

• Concentrates bile constituents including bile salts, cholesterol, lecithin and Bilirubin

Gall Bladder Emptying: Bile is conc. 5 folds but can be up to 20 folds Gallbladder emptying depends on secretion of CCK (initiated by fatty food) Less strongly by parasympathetic fibers of Vagi Gallbladder empties completely in about one hour

FUNCTIONS OF LIVER

1. CARBOHYDRATE METABOLISM a. Formation and storage of glycogen • Liver converts glucose to glycogen (glycogenesis) and prevents postprandial hyperglycemia [after carbohydrate meal] which could result in glucosuria • Normal glycogen store is 6% of liver mass • Sufficient for 12 hrs energy requirements

b. Conversion of glycogen to glucose • Glycogenolysis; between meals and helps to maintain normal blood glucose level during fasting

CARBOHYDRATE METABOLISM c. Gluconeogenesis ▪

Primary site for formation of glucose from non carbohydrate compounds e.g. glycerol, lactic acid and amino acids

d. Conversion of monosaccharides ▪

Fructose and galactose into glucose

e. Glucose-buffer function to maintain normal levels of blood glucose

2. PROTEIN METABOLISM a. Formation of plasma proteins i. Albumin, alpha and beta globulins ii. Plasma clotting factors e.g. fibrinogen, prothrombin, factors V, VII, IX and X iii. Acute phase proteins in response to stress iv. Transport proteins • 10 grams/ day albumin is produced normally

PROTEIN METABOLISM b. Inter-conversion of A. Acids by Transamination and Transpeptidation

c. Break down of amino acids by deamination • •

for conversion into carbohydrates or fats for energy production

d. Formation of urea: • • • •

for removal of ammonia (which is very toxic) formed by the break down of amino acids by bacterial flora of gut or by deamination

3. LIPID METABOLISM a. Beta-oxidation of fatty acids to form Acetyl-CoA; Acetyl-CoA → energy → acetoacetic acid (ketone bodies)

b. Conversion of A. Acids & Carbohydrates into TGs & FFA for storage of energy (for 6-8 wks)

c. Formation of triglycerides and lipoproteins (VLDL), cholesterol, phospholipids e.g. lecithin, cephalin. uptake of plasma LDL

d. Formation of Bile Acid from cholesterol 80% liver cholesterol converted into bile salts 20% liver cholesterol transported as lipoproteins

4. DETOXIFICATION OF BLOOD • Phagocytosis by Kupffer cells …. Cleansing action of liver • Biochemical inactivation of Xenobiotics & other toxins by Cyt-450 e.g. drugs, steroid hormones, ethanol (Toxic to liver if in excess)

• Convert toxic substances produced within the body (indole, ammonia, dopamine) or taken orally (drugs, food preservatives) to non – toxic derivatives

• The inactivated substances are excreted in urine or in bile • Liver inactivates several hormones e.g. thyroxin, estrogens, steroids etc

5. STORAGE OF VITAMINS & IRON • • • • •

Vitamin D storage for 4 months use Vitamin A storage for 10 months use Vitamin B12 storage for 1 yr Iron store as (ferritin) Copper storage

6. BILE SECRETION • Formed at rate of 23 ml/ hr during waking hours,

15ml/ hr during sleep  FORMATION OF BILE • Secreted by: 1. Hepatocytes (bile acids ,cholesterol and other organic constituents) 2. Cells lining the ducts and ductules (Na+,HCO3-,and H2O) • Role of Secretin in controlling bile secretion

COMPOSITION OF BILE • Water • Bile salts • Bilirubin • Cholesterol • Fatty acids • Lecithin • Na+, K+, Cl-, Ca++ HCO3-

7. METABOLISM OF BILE SALTS AND BILE ACIDS • These are Sterols derived from Cholesterol • Most important bile acids are CHOLIC ACID and CHENODEOXYCHOLIC ACID • Conjugated with glycine and taurine to form Bile Salts and in this form appear in hepatic bile • Most bile salts which enter intestine are reabsorbed → reach liver via portal blood → again secreted into bile • Help in digestion and absorption of lipids and vitamins (fat soluble) • 0.8 g/day by liver.

8. FORMATION OF BLOOD CELLS • In intra uterine life, liver is concerned with formation of red blood cells • But this function is lost at birth • Potential remains intact

9. CONJUGATION OF BILIRUBIN • Conjugated bilirubin: Bilirubin is conjugated with glucuronic acid by the enzyme glucuronyltransferase making it soluble in water

10. AS A BLOOD RESERVOIR • Liver is an expandable organ • Large quantities of blood can be stored in its blood vessels • Normal blood volume (hepatic veins + hepatic sinuses = 450 ml) • Right atrium pressure increases----back pressure in the liver---the liver expands • 0.5 to 1 liter of extra blood can be stored in the hepatic veins and sinuses • Condition – Cardiac failure

Regulation of Liver Mass — Regeneration • After partial hepatectomy or acute liver injury • Remarkable ability … Hepatocytes replicate once or twice • As long as the injury is uncomplicated by viral infection or inflammation • Partial hepatectomy --- up to 70 per cent of the liver is removed--- the remaining lobes enlarge and restore the liver to its original size • Remarkably rapid and requires only 5 to 7 days • The hepatocytes revert to their usual quiescent state --- once original size and volume of the liver are achieved

Regulation of Liver Mass — Regeneration • Hepatocyte growth factor (HGF) • produced by mesenchymal cells in the liver and in other tissues, but not by hepatocytes • Growth factors – epidermal growth factor – cytokines such as tumor necrosis factor – interleukin-6 • Main terminator of liver regeneration – transforming growth factor-β a cytokine secreted by hepatic cells

JAUNDICE ➢ Excess bilirubin in extracellular fluid ➢ Jaundice refers to a yellowish tint to the body tissues, including a yellowness of the skin and deep tissues.

➢ Usual cause of Jaundice is large quantities of bilirubin in extracellular fluids …. either unconjugated or conjugated billirubin

JAUNDICE • BILIRUBIN LEVELS: • Total Serum Bilirubin (normal) 0.2 - 0.8 mg/dl • JAUNDICE appears when Serum Bilirubin > 1.5mg/dl • Increased plasma concentrations of bilirubin (> 1.5mg/dl) occurs when there is an imbalance between its production and excretion ….. Hyperbilirubinemia (clinically recognized as Jaundice) • Levels can rise to as high as 40 mg/dl (KERNICTERUS ---- brain damage, mental retardation)

JAUNDICE • 75% of bilirubin is derived from RBCs • In normal adults this results in a daily load of 250-300 mg of bilirubin • Normal plasma concentrations are less then 1 mg/dl • Bilirubin is hydrophobic – transported by albumin to the liver for further metabolism prior to its excretion

Causes of Jaundice • Excessive Hemolysis • Impaired Bilirubin Transport – Congenital Hyperbilirubinemia • Hepatocellular Damage – Viral ,Toxins, Drugs, Alcohol, Shock, Congestion, Hypoxia • Impaired Bile flow – Cholestasis – Obstruction --- intra hepatic & extra hepatic • Reduced Functional Tissue Mass – Cirrhosis

JAUNDICE • CLASSIFICATION Pre Hepatic (Hemolytic) Hepatic (Hepatocellular) Post Hepatic (Obstructive )

Symptoms of Jaundice • Yellowing of the skin, scleras (white of the eye), and mucous membranes (jaundice) • Detectable when total plasma bilirubin levels exceed 2mg/dl

PRE HEPATIC / HEMOLYTIC JAUNDICE 

Increased destruction of RBCs with rapid release of bilirubin in the blood



Excretory function of Liver is normal but cannot excrete bilirubin as rapidly as it is formed

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The plasma conc. of Free Bilirubin increases along with increased Urobilinogen in blood

PRE HEPATIC / HEMOLYTIC JAUNDICE • Excess RBC lysis is commonly the result of • Autoimmune disease; Hemolytic disease of the newborn (Rh- or ABO- incompatibility); • Structurally abnormal RBCs (Sickle cell disease); OR • Breakdown of extravasated blood

➢Prolonged hemolysis may lead to precipitation of bilirubin salts in the gall bladder and biliary network ➢Result in formation of gallstones and conditions such as cholecystitis and biliary obstruction

Extravascular Pathway for RBC Destruction (Liver, Bone marrow, & Spleen) Phagocytosis & Lysis Hemoglobin

Globin

Amino acids

Amino acid pool

Heme

Bilirubin

Fe2+ Excreted

HEPATIC / HEPATOCELLULAR JAUNDICE • Impaired uptake, conjugation, or secretion of bilirubin • Reflects a generalized liver (hepatocyte) dysfunction, e.g In Hepatitis, Cirrhosis, Liver cancer

• In this case, hyperbilirubinemia is usually accompanied by other abnormalities in biochemical markers of liver function

POST HEPATIC / OBSTRUCTIVE JAUNDICE • Caused by: Obstruction of Biliary tree …Obstruction of Bile ducts due to Gallstones or Tumor of CBD (common bile duct) Damage to Hepatic Cells (in Hepatitis) ➢ Rate of Bilirubin formation is normal ➢ Formed Bilirubin cannot pass from blood into intestines

OBSTRUCTIVE JAUNDICE • Free Bilirubin still enters Hepatocytes, is conjugated and then returns to blood, by rupture of congested bile canaliculi and direct emptying of bile into lymph leaving the liver • Plasma bilirubin is conjugated, and other biliary metabolites, such as bile acids accumulate in the plasma • Characterized by pale colored stools (absence of fecal bilirubin or urobilin), and dark urine (increased conjugated bilirubin)

1.

Increased bilirubin production

2.

Reduced bilirubin uptake by hepatic cells

3. Disrupted intracellular

Lead to increases in free (unconj.) bilirubin

conjugation 4. Disrupted secretion of bilirubin into bile canaliculi 5. Intra/extra-hepatic bile duct obstruction

Result in rise in conj. bilirubin levels

Diagnostic Difference Between Hemolytic And Obstructive Jaundice 

Van den Bergh Test is used to differentiate  

Hemolytic -------- indirect +ve Obstructive ------- direct +ve

Van den Bergh Reaction: • Addition of sulfanilic acid to bilirubin pigments leads to formation of diazo compounds which are measured colorimetrically

- Direct reaction: is the resultant color change from the reaction of conjugated fraction which reacts immediately after the addition of the reagent to the solution - Total bilirubin: the amount of change in color resulting after the addition of methanol which leads to breaking down of the intramolecular hydrogen bonds of unconjugated bilirubin reacting with sulfanilic acid - Indirect fraction is the total amount of bilirubin minus the direct fraction.

BILIRUBIN