Download - Physiology of liver
OVERVIEW OF METABOLIC
FUNCTIONS OF LIVER
Brajesh Lahri
Final Professional MBBS ,All India Institute of Medical Sciences(AIIMS),Bhopal
Vitamin Storage
Maintaining iron reserves (Ferritin storage) and production of anti-coagulants
Detoxification
CARBOHYDRATE METABOLISM
Storage of glycogen
Conversion of galactose and fructose to
glucose
Gluconeogenesis
GLUCOSE BUFFER FUNCTION
Elevated blood glucose
LiverGlycogen formation
Normal blood glucose
Fall in blood glucose
Liver GlycogenlysisNormal blood
glucose
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
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
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
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 .
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.
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.
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.
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)
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
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.
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
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
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
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.
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.
WHEN BLOOD IRON LEVEL IS HIGH
Transferriniron in blood
liverFree iron (Fe3+)
Fe3+Fe2+
Fe2+ + apoferritin
ferritin
WHEN BLOOD IRON IS LOW
Transferrin-iron in blood
liver Release of
iron
Fe3+Fe2+
Fe2+ + apoferritin
ferritin
LIVER: A SITE OF PRODUCTION OF CLOTTING
FACTORS
XIIXIIa
XIXIa
IXIXa
XXa
ProthrombinThrombin
Fibrinogen Fibrin
VIIAIIa
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
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