Hb Synthesis, Degradation, Jaundice, Iron Metabolism by Dr. Roomi

8/12/2019 Hb Synthesis, Degradation, Jaundice, Iron Metabolism by Dr. Roomi

1/23

BLOOD PHYSIOLOGY

Hb Synthesis, degradation, jaundice andIron metabolism

By

Dr. Mudassar Ali Roomi (MBBS, M. Phil)

Assistant Professor Physiology


2/23

Formation of hemoglobin


3/23

Formation of

hemoglobin

Synthesis of Hb begins in theproerythroblasts and continueseven into the reticulocyte stageof the RBCs. MCQ

Steps of hemoglobin synthesis:

1. succinyl-CoA binds with glycineto form a pyrrole molecule(Mitochondria) MCQ

2. four pyrroles combine to formprotoporphyrinI X, which thencombines with iron to form theheme molecule.

3. Finally, each heme moleculecombines with a globin chainforming a subunit of Hb calleda Hb chain

4. Each chain has a molecularweight of about 16,000; four ofthese in turn bind togetherloosely to form the whole Hbmolecule.

5. Hb has a molecular weight of

about 64,000.


4/23

Figure 326

Basic structure of Hb

molecule, showing one

of the

four heme chains that

bind together to formthe Hb molecule.

Oxygen does not combine with the

two positive

bonds of the iron in the hemoglobin

molecule. Instead,

it binds loosely with one of the so-

called coordinationbonds of the iron atom. MCQ


5/23

four molecules of oxygen (or eight

oxygen atoms) can be transported by

each Hb molecule. MCQ


6/23

Normal Types of Hb in humans

= alpha, = beta, = gamma, = delta, = epsilon, =zeta

In the embryo: Gower 1 (22)

Gower 2 (22)

In the fetus: Hemoglobin F (22) MCQ

In postnatal people: Hemoglobin A (22) The most common with a normal amount

over 95%. MCQ

Hemoglobin A2(22) chain synthesis begins late in the thirdtrimester and, in adults, it has a normal range of 1.53.5%.MCQ


7/23

Variant forms of Hb that cause disease:

Hemoglobin S (2S

2)A beta chain variant

form of Hb found in people withsickle cell

disease.

Hb C (2C

2)Another variant due to a

variation in the -chain gene.


8/23

FATE OF RED BLOOD CELLS

Life span in blood stream is 120days. MCQ

old and fragile RBCs are phagocytosed and are lysed.

Normally, lysis occurs extravascularly in the reticuloendothelial system subsequent

to RBC phagocytosis.

Lysis can also occur intravascularly (in blood stream) .


9/23

PATHWAY FOR RBC DESTRUCTION

Lysis in: Liver, Bone marrow,

& Spleen

Hemoglobin

Globin

Amino acids

Amino acid pool

Heme Bilirubin

Fe2+

Excreted

Phagocytosis & Lysis

Recycled


10/23

DEGRADATION OF HEME TO BILIRUBIN

P450cytochrome

85% bilirubin is derived from heme

as a result of RBC degradation.

In normal adults this results in a

daily load of 250-300 mg of bilirubin

but liver has the ability to conjugate

3000mg /day of bilirubin.

Normal plasma concentration ofbilirubin is < 1 mg/dl and jaundice

occurs usually at conc. Is > 2mg/dl.

MCQ

bilirubin is Hydrophobicor water

insoluble and is transported byalbuminto the liver for further

metabolism prior to its excretion.

unconjugated bilirubin


11/23

Heme CatabolismHeme Degradation

HEME

BILIVERDIN

O2

Fe+3

NADPH

NADP+

(opens the porphyrin ring)

BILIRUBIN

NADPH

NADP+

BILIRUBIN diglucuronide

BILE


12/23


13/23

JAUNDICE

Due to Hyperbilirubinemia(greater than 2mg/dl):

Two forms of

bilirubin: Direct bilirubin: Conjugated

with glucoronic acid and issoluble in water.

Indirect bilirubin:unconjugated, insoluble inwater.


14/23

DIFFERENCES BETWEEN

UNCONJUGATED BILIRUBIN

Insoluble in water.

Cannot be excreted in urine.

Can deposit inbrain(kernicterus).

Plasma level increases in

pre-hepatic jaundice.

CONJUGATED BILIRUBIN

Soluble in water.

Can be excreted in urine.

Cannot be deposited inbrain.

Plasma level increases in

hepatic and post-hepaticjaundice.


15/23

Hemolytic jaundice

excess

hemolysis


(in blood)

conjugated bilirubin

(released to bile duct)

Hepatocellular jaundice


(in blood)


(in blood)

Obstructive jaundice


(in blood)


(in blood)


16/23

PREHEPATIC (HEMOLYTIC) JAUNDICE

Results from excess production

of bilirubin (beyond the liversability to conjugate it) followinghemolysis.

Excess RBC lysis is commonly

the result of hemolytic diseases,structurally abnormal RBCs(Sickle cell disease).

High plasma concentrations ofunconjugated bilirubin (normalconcentration ~0.5 mg/dL)


17/23

INTRAHEPATIC JAUNDICE

Impaired uptake,conjugation, or secretion ofbilirubin

Reflects a generalized

liver (hepatocyte)dysfunction

In this case,

hyperbilirubinemia isusually accompanied byother abnormalities inbiochemical markers ofliver function


18/23

POSTHEPATIC JAUNDICE

Caused by an obstruction of the

biliary tree.

Plasma bilirubin is conjugated, andother biliary metabolites, such asbileacidsaccumulate in theplasma which causes itching.

Characterized by paleor claycolouredstools(absence of fecalbilirubin or urobilin), and darkurine (increased conjugated

bilirubin)

In a complete obstruction,urobilin is absent from the urine


19/23

DIAGNOSES OF JAUNDICE


20/23

NEONATAL JAUNDICE

Common, particularly in premature infants

Transient (resolves in the first 10 days)

Due to immaturity of the enzymes involved in bilirubin conjugation

High levels of unconjugated bilirubin are toxic to the newborn due toits hydrophobicity it can cross the blood-brain barrier and cause a type

of mental retardation known as kernicterus. MCQ

If bilirubin levels are judged to be too high, then phototherapywithUV light is used to convert it to a water soluble, non-toxic form


21/23

IRON METABOLISM


22/23

iron is important for the formation of: hemoglobin,myoglobin, cytochromes, cytochrome oxidase,peroxidase and catalase. MCQ

The total iron in the body 4 to 5 grams:

65 %in the form of Hb 4 %in the form of myoglobin,

1 % in cytochromes,

0.1 % is combined with the protein transferrin in the bloodplasma

15 to 30 per cent is stored for later use, mainly in thereticuloendothelial system and liver parenchymal cells,principally in the form of ferritin.


23/23

Transport and Storage of Iron

TRANSPORT FORM OF IRON=

MCQ

STORAGE FORM OF IRON=

soluble form of iron. MCQ

insoluble form of iron.MCQ

Daily Loss of Iron:

A man excretes about 0.6 mgFe/day, mainly into the feces.

In a woman Fe loss is about 1.3 mg/day.

Hb Synthesis, Degradation, Jaundice, Iron Metabolism by Dr. Roomi

Documents