1. Liver Functional unit: Hepatocyte Hexagonal lobules Vascular sinusoids
Dr Jaria Fatahia
11/17/2018

2. Dr Jaria Fatahia
11/17/2018

3. Liver lobules Liver lobules – hexagonal structures .
Hepatocytes radiate outward from a central vein
At each of the six corners of a lobule is a portal triad
Liver sinusoids
Liver lobules – hexagonal structures consisting of hepatocytes
Hepatocytes radiate outward from a central vein
At each of the six corners of a lobule is a portal triad
Liver sinusoids
Sinusoids are low pressure vascular channels that receive blood from terminal branches of the hepatic artery and portal vein at the periphery of lobules and deliver it into central veins. Sinusoids are lined with endothelial cells and flanked by plates of hepatocytes
11/17/2018
Dr Jaria Fatahia

4. Hepatocytes produce bile
Bile flows through canals called bile canaliculi to a bile duct
Bile ducts leave the liver via the common hepatic duct
11/17/2018
Dr Jaria Fatahia

5. Bile
BILE – bile salts, bile pigments, cholesterol, neutral fats, phospholipids and electrolytes
Liver produces l of bile daily
Dr Jaria Fatahia
11/17/2018

6. Dr Jaria Fatahia
11/17/2018

7. Functions Metabolic Synthesis Breakdown
Other functions – storage of vitamin A,D,B12,F…
Excretion of waste products from bloodstream into bile
Vascular – storage of blood
Dr Jaria Fatahia
11/17/2018

8. Protein metabolism Synthesis of amino acids
Formation of plasma proteins
Albumins, globulins
Clotting factors
Transamination & transpeptidation
Deamination
Urea ccle
Formation of nitrogen containing compounds
N containing compounds :Porphyrins,Creatine,Neurtransmitters,Purines,Pyrimidine
Dr Jaria Fatahia
11/17/2018

9. Protein metabolism
Produces albumin the major osmolar component of blood serum
Synthesizes angiotensinogen, the hormone responsible for raising blood pressure when activated by renin (enzyme released when the kidney senses low blood pressure)
Dr Jaria Fatahia
11/17/2018

10. Carbohydrate Metabolism
Formation & storage of glycogen
Conversion of glycogen to glucose
Gluconeogenesis
Conversion of fructose & galactose to glucose
Dr Jaria Fatahia
11/17/2018

11. Lipid Metabolism Formation of ketone bodies Formation of TG & VLDL
Cholesterol
Saturation & desaturation of FA
Uptake of plasma LDL
Bile, Bile salts, bile acids
Bile pigment metabolism
Dr Jaria Fatahia
11/17/2018

12. Breakdown Breaks down insulin and other hormones
Breaks down hemoglobin
Breaks down or modifies toxic substances (methylation) → sometimes results in toxication
Converts ammonia to urea
Dr Jaria Fatahia
11/17/2018

13. Breakdown
Hb:
Globin
Iron
Porphyrin part
11/17/2018
Dr Jaria Fatahia

14. 11/17/2018
Dr Jaria Fatahia

15. The catabolism of hemoglobin is outlined in the graphic on the left
The catabolism of hemoglobin is outlined in the graphic on the left. Red blood cells are continuously undergoing a hemolysis (breaking apart) process. The average life-time of a red blood cell is 120 days. As the red blood cells disintegrate, the hemoglobin is degraded or broken into globin, the protein part, iron (conserved for latter use), and heme (see middle graphic). The heme initially breaks apart into biliverdin, a green pigment which is rapidly reduced to bilirubin, an orange-yellow pigment (see bottom graphic). These processes all occur in the reticuloendothelial cells of the liver, spleen, and bone marrow. The bilirubin is then transported to the liver where it reacts with a solubilizing sugar called glucuronic acid. This more soluble form of bilirubin (conjugated) is excreted into the bile.
The bile goes through the gall bladder
Dr Jaria Fatahia
11/17/2018

16. In the human body approx
In the human body approx. 100 – 200 million ery are broken down every hour. Degradation of Hb begins in ER of reticuloendothelial cells (RES) of the liver, spleen, bone marrow and skin.
Hb is degraded to:
● globins → AAs → metabolism
● heme → bilirubin
● Fe2+ → transported with transferrin and used in the next heme biosynthesis
Not only Hb but other hemoproteins also contain heme groups which are degraded by the same pathway
Dr Jaria Fatahia
11/17/2018

17. Extravascular Pathway for RBC Destruction
(Liver, Bone marrow,
& Spleen)
Phagocytosis & Lysis
Hemoglobin
Globin
Heme
Bilirubin
Amino acids
Fe2+
Amino acid pool
Excreted
11/17/2018
Dr Jaria Fatahia

18. Heme Degradation  75% is derived from RBCs
In normal adults this results in a daily load of mg of bilirubin
Normal plasma concentrations are less then 1 mg/dL
Hydrophobic – transported by albumin to the liver for further metabolism prior to its excretion
Dr Jaria Fatahia
11/17/2018

19. Uptake of bilirubin by the liver is mediated by a carrier protein (receptor)
Uptake may be competitively inhibited by other organic anions
On the smooth ER, bilirubin is conjugated with glucoronic acid, xylose, or ribose
Glucoronic acid is the major conjugate - catalyzed by UDP glucuronyl tranferase
“Conjugated” bilirubin is water soluble and is secreted by the hepatocytes into the biliary canaliculi
Converted to stercobilinogen (urobilinogen) (colorless) by bacteria in the gut
Oxidized to stercobilin which is colored
Excreted in feces
Some stercobilin may be re-adsorbed by the gut and re-excreted by either the liver or kidney
Dr Jaria Fatahia
11/17/2018

20. Hemoglobin dissociates into Heme & globin Porphyrin ring is cleaved
Oxidation of alpha methylene bridges
Heme loses one molecule of CO & one atom of iron in ferric form
Biliverdin ( biliverdin reductase)
Bilirubin
Dr Jaria Fatahia
11/17/2018

21. Biliverdin
Dr Jaria Fatahia
11/17/2018

22. Bilirubin (Bil) is released from RES into the blood. BUT
Bilirubin (Bil) is released from RES into the blood. BUT! Bil is only poorly soluble in plasma, and therefore during transport it is bound to albumin („nonconjugated Bil“). ↓
LIVER
In the hepatocytes, Bil is conjugated by 2 molecules of glucuronic acid → bilirubin diglucuronide (soluble in water, „conjugated Bil“)
BILE
INTESTINE
Bil is reduced to urobilinogen and stercobilinogen
Dr Jaria Fatahia
11/17/2018

23. Conjugation
bilirubin-diglucuronide = conjugated bilirubin is soluble in water → „direct bilirubin“
Urobilinogen and stercobilinogen can be:
reabsorbed and returned to the liver
(= enterohepatic circulation)
b) oxidized (in the presence of O2) to pigments urobilin (orange) and stercobilin (yellow) → they are excreted in the stool
Urobilinogen also appears in the urine.
Dr Jaria Fatahia
11/17/2018

24. Bile pigments:
bilirubin
urobilin
stercobilin
Blood tests
Bil reacts directly when reagents are added to the blood sample → conjugated bilirubin = direct Bil (up to 3.4 µmol/L)
free Bil does not react to the reagents until alcohol (methanol) or caffeine is added to the solution. Therefore, the measurement of this type of bilirubin is indirect → unconjugated bilirubin = indirect Bil (up to µmol/L)
total bilirubin measures both unconjugated and conjugated Bil (normal value up to 17 µmol/L).
Dr Jaria Fatahia
11/17/2018

25. Liver Function Tests
Dr Jaria Fatahia
11/17/2018