An overview of physiological functions of Liver

1. OVERVIEW OF METABOLIC
FUNCTIONS OF LIVER
Brajesh Lahri
Final Professional MBBS ,All India Institute
of Medical Sciences(AIIMS),Bhopal

2. METABOLIC FUNCTIONS OF LIVER
Carbohydrate metabolism
Fat metabolism
Protein metabolism

3. Vitamin Storage
Maintaining iron reserves (Ferritin
storage) and production of anti-coagulants
Detoxification

4. CARBOHYDRATE METABOLISM
Storage of glycogen
Conversion of galactose and fructose to
glucose
Gluconeogenesis

5. GLYCOGEN STORAGE

6. GLUCOSE BUFFER FUNCTION
Elevated
blood glucose
Liver
Glycogen
formation
Normal blood
glucose
Fall in blood
glucose
Liver Glycogenlysis
Normal blood
glucose

7. CARBOHYDRATE METABOLISM

Conversion of galactose and fructose to
glucose
Gluconeogenesis

8. IF YOU REMEMBER?

9. CARBOHYDRATE METABOLISM


Gluconeogenesis

10. GLUCONEOGENESIS
 Brain depends on glucose as its primary fuel and red
blood cells use glucose as their only fuel.
 Daily requirement=160 g
 Glycogen stores= 190 g of glucose

11. Fall in blood
glucose
Liver Glycogenlysis
Normal blood
glucose

12. PROLONGED STARVATION
Depletion of glycogen stores
Fall in glucose levels
Non carbohydrate substances
lactate, amino acids, and glycerol
 Gluconeogenesis in the liver and kidney
helps to maintain the glucose level in the
blood so that brain and muscle can
extract sufficient glucose from it to meet
their metabolic demands

13. LIPID METABOLISM

14. OVERVIEW OF ROLE OF LIVER IN LIPID
METABOLISM
Metabolism of
Lipids
Anabolism
Synthesis of de
novo cholesterol
and fatty acids
Synthesis of fat
from proteins and
carbohydrates
Catabolism
Oxidation of fatty
acids to supply
energy for body
functions

15. DE NOVO SYNTHESIS OF CHOLESTEROL AND
FATTY ACIDS
Occurs in Liver as well as in peripheral
tissues.
For fatty acid synthesis as well as
cholesterol synthesis immediate
substrate is Acetyl CoA .

17. SYNTHESIS OF FATS FROM CARBOHYDRATES
AND PROTEINS
• Acetyl CoA from
metabolism of Carbon
skeleton of proteins
• Acetyl CoA from
metabolism of
carbohydrates
Acetyl CoA enters
lipogenesis
pathway.

18. BETA OXIDATION OF FATTY ACIDS

19. OXIDATION OF FATTY ACIDS TO PROVIDE
ENERGY

20. PROTEINMETABOLISM

21. MOST IMPORTANT FUNCTIONS OF LIVER
IN PROTEIN METABOLISM
 Deamination of amino acids
 Formation of urea for removal of ammonia
 Formation of plasma proteins
 Interconversions of the various amino acids and
synthesis of other compounds from amino acids.

22. DEAMINATION OF AMINO ACIDS
 Required before amino acids can be used for
energy or converted to carbohydrates or fats.
 Small amount of deamination occurs in other
tissues especially in kidney
 Most important site - liver.

23. UREA FORMATION
• Deamination
• In gut, by
bacteria(small
amounts)
Ammonia
Formation
• Ammonia
enters urea
cycle
Urea Formation
• Hepatic coma
• Death
avoided
Avoids ammonia
intoxication
Note: Ammonia freely permeable across blood brain barrier
Ammonia intoxication occurs in
• Severely impaired hepatic function
• Cirrhosis(Collaterals between portal and systemic veins)

25. UREA FORMATION

26. FORMATION OF PLASMA PROTEINS
 Essentially all plasma proteins, except gamma globulins.
 Serum albumin quantitatively the most important
protein synthesized by the liver.
 In all chronic liver diseases, serum albumin level is
decreased.
 Reversal in A/G ratio occurs in liver cirrhosis, due to
hypoalbuminemia and associated
hypergammaglobulinemia.
 Other plasma proteins
 Acute phase proteins
 Clotting factors
 Transport proteins eg. For steroids, hormone transport

27. AMINO ACID METABOLISM
 Synthesis of non-essential amino acids.
 Keto acid having same chemical composition as that of
the amino acid to be formed is synthesized.
 Transamination from an available amino acid is done.
Pyruvat
e
Alanine
Glu or Asp α-ketoglutarate or
oxaloacetete
Eg.

28. AMINO ACIDS
Essential amino acids
• Arginine
• Histidine
• Isoleucine
• Leucine
• Lysine
• Methionine
• Phenylalanine
• Threonine
• Tryptophan
• Valine
Non Essential Amino Acids
• Alanine
• Asparagine
• Aspartate
• Cysteine
• Glutamate
• Glutamine
• Glycine
• Hydroxyproline
• Hydroxylysine
• Proline
• Serine
• Tyrosine

29. STORAGE OF VITAMINS IN LIVER

30. VITAMINS STORED IN LIVER
Vitamin-A
Vitamin-D
Vitamin-B12

31. VITAMIN-A
Vitamin A is stored in greatest quantity
Maintains blood plasma levels of vitamin A
Prevents vitamin A deficiency for 10 months
MECHANISM OF UPTAKE,STORAGE AND RELEASE OF VITAMIN A
o Vitamin A (Retinol) is transported in chylomicrons as ester of fatty
acids
o Chylomicrons enter circulation;acted on by lipoprotein lipase
o Triglyceride part is reduced;retinyl ester remains unchanged
o Receptors in liver mediate uptake of chylomicron remnants.
o Chylomicron remnants are degraded and retinyl ester is stored
o Liver mobilizes vitamin A by hydrolyzing retinyl ester
o Retinol formed will be bound to retinol binding
protein(RBP),synthesized by liver

32. HYPERVITAMINOSIS- A
 Develops when massive quantities of vitamin A is
consumed
 Hepatotoxicity is often associated with
hypervitaminosis A
 Eventually leads to portal hypertension and
cirrhosis

33. VITAMIN- D AND B12
 Liver also stores vitamin D and vitamin B12
 Liver helps in the activation of vitamin D.
 Prevents vitamin D deficiency for 3 to 4 months.
 Enough vitamin B12 can be stored in liver for
atleast 1 year.

34. LIVER: A STORAGE SITE FOR IRON

35. IRON STORAGE IN LIVER
 Liver stores iron mainly in the form of ferritin.
 Iron from transferrin in blood transfers to liver and
combines with apoferritin to form ferritin.

36. WHEN BLOOD IRON LEVEL IS HIGH
Transferrin
iron in
blood
liver
Free iron
(Fe3+)
Fe3+Fe2
+
Fe2+ +
apoferritin
ferritin

37. WHEN BLOOD IRON IS LOW
Transferrin-
iron in
blood
liver
Release of
iron
Fe3+Fe2
+
Fe2+ +
apoferritin

ferritin

38. Thus apoferritin-ferritin system of liver acts as
 blood iron buffer as well as
 iron storage medium.

39. LIVER: A SITE OF PRODUCTION OF CLOTTING
FACTORS
XIIXIIa
XIXIa
IXIXa
XXa
Prothrombin
Thrombin
Fibrinogen
Fibrin
VIIAIIa

40. Liver produces :
1)Factor VII
2)Factor IX
3)Factor X
4)Fibrinogen
5)Prothrombin
Extrinsic
System

41. ROLE OF LIVER IN DETOXIFICATION

42.  Liver detoxifies blood of substances originating
from gut or elsewhere in the body
 Can be through physical methods or biochemical
reactions
 Metabolites are secreted into bile and eliminated
through GIT

43. Liver
detoxification
Physical
methods
Kupffer cells
Biochemical
reactions
Cyt P450
enzymes
mediated

44. Phase I
oxidation
hydroxylation
Cyt P450
mediated
Phase II
esterification

45. HEPATIC ENCEPHALOPATHY
 Increased level of circulating ammonia due to liver
failure.
 Cause-
 Loss of functional hepatocytes
 Shunting of portal blood
 Symptoms-
 Confusion
 Coma and irreversible change in cognition if untreated