1. Abnormalities of Red Cell membrane Lecture NO: 1st MBBS
Dr Muhammad Ramzan

2. Red cell membrane abnormalities – the definition
These are the inherited diseases due to mutations in various membranous or/and skeletal proteins of the red cell
It results in ↓passive deformation, life span and premature removal of RBC from circulation by Haemolysis
These include Hereditary Spherocytosis, Elliptocytosis and Somatocytosis
Hereditary RBC membrane defects----. Wilma Barcellini.Blood Tranf2011. July;9(3):

3. Integrity of cell membrane – the background Mutation of skeletal proteins changes RBC shape
Integrity of the Red cell membrane is maintained by the vertical interaction B/W Lipid Bilayer and membrane skeleton
Mutation of the skeletal proteins leads to secondary defects in Spectrin assembly and unstable RBC membrane
RBC changes from discoid to sphere; loses passive deformation,
Trapped in capillaries, haemolyzed and results in anaemia 2
Pediatrics in Review; May VOLUME 25/ISSUE 5

4. RBC integrity - Vertical Interaction B/W Lipid Bilayer and cytoskeleton

5. Normal RBC – the morphology Passive deformation
RBC is a biconcave disc like a rounded ball that appears wider at the ends and narrowest in the middle :
when squeezed from 2 opposite ends
Its average diameter is 7.8µm and 2µm in thickness ,However, Its thickness is < 1 mµ in the center
Red cell has high surface area relative to cell volume that helps in rapid diffusion of respiratory gases
Has the ability of passive deformation ( changes to < 1/3 of its diameter)
( Healthhype.com)

6. Red cell - Morphology

7. Red Cell – the characteristics

8. Red cell membrane - the characteristics the only structural component
RBC is unique among the body cells that its plasma membrane accounts for all of its characteristics.
These include: antigenic; transport (anions) and ability to undergo passive deformation(1/3) during its passage through:
microvasculature especially in spleen)
 ↑surface area relative to intracellular volume
Helps in rapid diffusion of Respiratory gases
Wilma Barcellini.Blood Tranfus July;9(3):

9. Red Cell passive deformation 1/3 of its diameter
It is the ability of the RBC to change and restores its shape after passing through microcirculation normally
It is due to 1. excess of plasma membrane and is carried out without its stretching and 2. flexibility of Cytoskeleton
Helps to complete the normal life span of RBC (120 days)
Prevents the RBC trapping, haemolysis and maintains blood flow
Red cell membrane; past, present and Future .2008
journal.org

10. Deformation of Red cell

11. Normal and damaged RBC

12. RBC membrane – the parts
The red blood cell membrane consists of 3 basic components:
A Lipid Bilayer,
Trans membrane (integral) proteins and
A Cytoskeleton network.   

13. RBC membrane – the parts

14. Lipid Bilayer – A semi permeable part of the plasma membrane
The lipid Bilayer is a semi permeable compartment of the plasma membrane that separates 2 aqueous ones :
The cytoplasm from the extracellular medium. 
It consist of Phospholipids ; CH, CH esters, u FA and proteins
It is liquid in nature that allows the lateral movements of integral proteins (prevents vertical movements)
Maintains the fluidity of the cell membrane

15. Phospholipid Bilayer – A subunit of RBC membrane

16. Tran membrane/Integral proteins the types `
Transmembrane proteins cross the lipid Bilayer and have lateral mobility in the membrane
Major ones are; Glycophorins ,Band3, Aquaporins and RHAG(Rhesus proteins)
The red cell glucose transporters (GLUT-1)
Band 3 is an ion transporter , a diamer
Band 3 Tetramer; crosses the lipid Bilayer.
Its Cytoplasmic domain interacts with the cytoskeleton via :
Ankyrin and Spectrin

17. Trans membrane Proteins of RBC

18. Tran membrane proteins - the role
Glycophorins, general proteins that contribute to Glycosalytion
Glycophorin C crosses the Bilayer to interact with Protein 4.1 with in the junctional complex of Cytoskeleton
Band 3 is an ion transporter(HCO3 for Cl++ ions)
Aquaporin is a membrane water channel protein
RH AG (Rhesus) proteins are associated with Band 3 and ABO blood group system
The red cell Glucose transporter(GLUT1) is passive one and is present in other tissues also.

19. Red cell integral proteins

20. Red cell proteins – Band3

21. The Cytoskeleton – A network of skeletal and Cytoplasmic portions of Tran membrane proteins
The cytoskeleton is an irregular hexagonal network of α and β Spectrin moles which are tied together mainly by the :
Ankyrin, Actin; Band 3 and other Skeletal proteins at nodes called the junctional complexes.
The skeleton makes a 2 D network which is very flexible and compressible and allows passive deformation of RBC

22. Red cell Cytoskeleton

23. Cytoskeleton - the Spectrin
Spectrin is the major component of the cytoskeleton. Major role is:
To provide support to the Lipid Bilayer
Maintains the cell shape
Regulates the lateral movement of the Integral proteins 3
It interacts with the membrane and Skeletal proteins by vertical and horizontal interactions
Dr Avinash Deo. February, 2014

24. Red cell Cytoskeleton

25. RBC – Cytoskeleton A hexagonal network

26. Disorders of RBC membrane the haemolytic anaemias
These disorders comprise a group of hemolytic anaemias that present with different clinical and laboratory findings
These include hereditary Spherocytosis; hereditary Elliptocytosis and hereditary Somatocytosis

27. Pathogenesis - Deformed RBC (spherical shape) loss of memb
Pathogenesis - Deformed RBC (spherical shape) loss of memb. Surface area to intra cellular volume
The primary cellular defect is the loss of membrane surface area relative to intracellular volume
Defects in Spectrin assembly leads to the :
Spherical shape of RBC from discoid one
Reduction in the ability of RBC for passive deformation 2
Lipids are lost from the lipid Bilayer as micro vesicles

28. Deformed RBC – the consequences
Change in the shape of RBC (to spherical) loses its ability to move freely in micro circulation (Splenic)
RBC are trapped, their membranes damaged that ↑ their chances for Haemolysis and :
their premature removal from the circulation
It results in haemolytic anaemia

29. Haemolytic anaemia

30. Hereditary Spherocytosis (HS)
HS is the most common red cell membrane disorder in children
Spherocytes are rounded Red cells that have lost the ability to change their shape (deformation)
Spherocytes cannot move freely in capillaries with short lifespan
Chronic haemolysis is the hallmark of HS
HS is diagnosed by the presence of spherical RBC on the Peripheral blood smear

31. Hereditary Spherocytosis