Transcript RED &WHITE BLOOD CELLS

RED &WHITE BLOOD CELLS
DR AMINA TARIQ
BIOCHEMISTRY
Blood has two distinct parts to it.
 Plasma, the fluid part of the blood, takes up
about 55% of the blood volume. Plasma is 91%
water with various other materials in solution
and suspension, such as dissolved proteins,
nutrients, electrolytes, hormones, and metabolic
wastes.

The cellular portion of blood normally makes
up about 45% of the blood volume.
 It consists primarily of white blood cells (WBCs),
platelets, and red blood cells (RBCs). The
white blood cells are the mobile elements of the
body's defense system. Platelets are small cell
fragments which play an important part in blood
clotting

RED BLOOD CELLS
Biomedical Importance
 Structure of Hb
 Function of Hb
 Porphyrias
 Jaundice
 Iron metabolism
 Anemias
STRUCTURE OF RBC
A very simple cell.
 Major function is to transport oxygen to the
tissues .
 And disposal of carbon dioxide and protons
formed by the tissue metabolism.
 Is composed of a membrane surrounding the
hemoglobin.
 Hb forms about 95% of the intracellular protein
of the red cell.

There are no intracellular organelles, such as
mitochondria, lysosomes or golgi apparatus.
 Non- nucleated.
 Metabolically is active.
 Biconcave shape increases the surface to volume
ratio of RBC, thus facilitating the gas exchange.
 Contain cytoskeletal components that play an
important role in determining its shape.

RBC contains certain enzymes of nucleotide
metabolism.
 At the end of their life span, globin is degraded to
amino acids which are reutilized in the body. Iron
is released from heme and also reutilized, and
porphyrins are converted to bilirubin.

Life span of RBC is 120 days.
 Production of red cells is regulated by
erythropoeitin.

Erythropoeitin:
 It is a glycoprotein of 166 amino acids.
 It is a major regulator of human erythropoiesis.
 It is synthesized mainly in the kidney.
 Is released in response to hypoxia into the blood
stream, and travel to bone marrow.
 There it interacts with the progenitor of red cells
-Burst forming unit-erythroid (BFU-E).
 Recombinant DNA (anemia of renal failure)
MEMBRANE OF RED CELL
Membrane is a lipid bilayer.50% lipids and 50%
proteins.
 Major lipids are phospholipids and cholesterol.
 Major phospholipids are: PC, PE,PS and
sphingomyelin.
 Choline containing phospholipids are in the outer
leaflet(PC, Sph).
 Amino containing phospholoipids are in the inner
leaflet (PE, PS).

Glycosphingolipids constitute about 5-10%.
 These constitute neutral GSLs, gangliosides and
complex species, including ABO blood group
substances.
 10 major proteins and 100 minor species.
 Major proteins include: spectrin, ankyrin,anion
exchange proteins, actin and band 4.1.
 Many of the proteins are glycoproteins.

ASPECTS OF RBC METABOLISM
Glucose dependent (glucose transporters).
 Anaerobic glycolysis for ATP production.
 No mitochondria, no oxidative phosphorylation.
 Transporters on the membrane.
 Production of 2,3 BPG.
 Pentose Phosphate pathway.
 Methemoglobin reductase.
 Synthesis of glycogen, fatty acids, proteins and
nucleic acids does not occur in the RBC.


Glucose Transporter – GLUT 1 is present on
RBC. It is an example of facilitated transport.
Not dependent on insulin. It generates a gated
pore in the membrane and to permit the passage
of glucose.

Transporters maintain the ionic and water
balance. It involves the movement of Cl⁻ and
HCO3( anion exchange protein). In RBC it is
called band 3. It is important in adjusting the
levels of RBC HCO3 ⁻ concentration in arterial
and venous blood.
DISORDERS AFFECTING RBCS
Iron deficiency anemia
 Methemoglobinemia
 Sickle cell anemia
 Thalassemias
 Megaloblastic anemias ( B12 , folic acid)
 Hereditary spherocytosis
 G6PD deficiency
 Pyruvate kinase deficiency
 Paroxysmal nocturnal hemoglobinemia

G6PD deficiency It is an inherited disorder.
 Characterized by the hemolytic anemia.
 Caused by the inability to detoxify oxidizing
agents.
 It is the most common disease producing enzyme
deficiency in the world.
 It is X-linked disorder.
Decreased G6PD activity impairs the ability of
the cell to form NADPH.
 Which is responsible for the maintenance of
reduced glutathione.
 Glutathione also helps maintain the reduced
states of sulfhydryl groups in proteins including
Hb.
 When these proteins are oxidized it leads to the
denaturation of these proteins.
 That form insoluble masses called Heinz Bodies.

These bodies attach to the red cell membrane.
 Membranes become rigid and deformable.
 G6PD deficiency occurs in all the cells , but is
most severe in RBCs.
 Because other cells are able to produce NADPH
by alternate pathway(NADP dependent malate
dehydrogenase).

Precipitating Factors:
 Oxidant drugs(AAA- antibiotics, antimalarials
and antipyretics).
 Favism.
 Infection.
 Neonatal jaundice
Caused by Missense point mutations.
 Variant forms:
1. G6PD A⁻ - Moderate form of disease.
2. G6PD Mediterranean – Severe form of disease.

PROTECTION OF RBC
Several powerful oxidants are produced in the
course of metabolism, in both blood cells and
other cells of the body.
 These include superoxide, hydrogen peroxide,
peroxyl radicals and hydroxyl radicals.
 These are known as reactive oxygen species.
 Superoxide dismutase, Catalase and Glutathione
protect red cell from these ROS.

SOD convert O⁻2 into H2O2.
 Catalase detoxify H2O2 to H2O.
 Glutathione also does the same.

NEUTROPHILS
BIOCHEMICAL FEATURES
Active glycolysis
 Active pentose phosphate pathway
 Moderate oxidative phosphorylation
 Rich in lysosomes.
 Unique enzymes and proteins. E.g.
myeloperoxidase , NADPH oxidase,
 Contain CD 11/ CD 18 integrins in plasma
membrane.

IMPORTANT ENZYMES & PROTEINS
Myeloperoxidase- responsible for the green color
of the pus. Deficiency causes chronic infections.
 NADPH oxidase- responsible for the respiratory
burst.
 Lysosomes- Abundant in macrophages.
 Defensins- Antibiotic peptide, kills bacteria by
causing membrane damage.

Lactoferrin- It is an iron binding protein, inhibits
growth of certain bacteria by binding iron.
 CD 11/ CD 18- Adhesion molecules.
 Receptors for the Fc fragment of IgGs- bind Fc
fragment of IgG molecule.
 Vasoactive biomolecules (plate activating factor,
eicosanoids).

PROTEINASES
Elastase
 Collagenase
 Gelatinase
 Cathepsin G
 Plasminogen activator

ANTIPROTEINASES
α-1 antitrypsin
 α-2 macroglobulin
 Secretory leukoproteinase inihibitor
 α-1antichymotrypsin
 Plasminogen activator inhibitor-1
 Tissue inhibitor of metalloproteinase.

ACTIVATION OF NEUTROPHILS
They are activated by specific receptors.
 By interaction with bacteria, chemotactic factors,
antigen-antibody complexes.
 Intracellular calcium rises and activates protein
kinase C.

RESPIRATORY BURST
It involves NADPH oxidase and helps kill
bacteria.
 There are two mechanisms – oxygen dependent
and oxygen independent for killing bacteria.

Oxygen independent mechanism:
 These involve pH changes in phagolysosmes
 And Lysosomal enzymes to kill bacteria.
Oxygen dependent mechanism:
 It includes myeloperoxidase system(MPO) and
NADPH oxidase system.
 It is the most potent bactericidal mechanism.
 Microorganism is internalized.
 NADPH oxidase converts molecular O2 into
superoxide radical.
 This rapid conversion is called respiratory burst.
 Then superoxide is spontaneously converted into
hydrogen peroxide.
This product is then neutralized by catalase or
glutathione peroxidase.
 In the presence of Myeloperoxidase which is a
lysosomal enzyme, Hydrogen peroxide plus
chloride ions are converted to hypochlorous acid.
 This kills the bacteria.
 Hypochlorous acid is the major component of
household bleach.

Mutations in the genes encoding NADPH oxidase
leads to a disease called chronic granulomatosis.
 In which severe chronic pyogenic infections occur.

LEARNING RESOURCES
Harpers Biochemistry
 Lippincott's Biochemistry
