Red cell membrane and its congenital disorders Flashcards
What percent of RBC weight is accounted for by red cell memebrane
1%
Functions of red cell memebrane
Maintains RBC integrity
provides flexibility so RBC can adjudt its shape\
Durability
Tensile strength
Maintains its structure
Metabolism
Acid base hemeostasis through pumps present in it
Cell membrane bilipid layer made mainly of
Cholesterol
Phospholipids
integral proteins for tensile strength and flexibility
Membrane skeleton for structure
lipids make up this percentage of red cell membrane
50-60%
Mainly phosphatidyl choline; inositol; serine; ethanolamine
Sphingomyelin
Function of cholesterol in membrane
Ensures membrane fluidity
Phospholipids distribution in Red cell membrane
Asymetrically distributed
phosphatidyl serine; ethanolamine inwards
Phosphatidyl choline , sphingomyelin outwards
Membrane proteins of red cell
- integral membrane proteins
eg .Band 3,Glycophorins ,Kidd ,Duffy, Rh proteins, Lutheran glycoprotein
2.Peripheral membrane proteins
eg sceptrin, ankyrin, protein 4.1, protein 4.2
Integral memebrane proteins
, a permanent part of membrane
most abundant integral glycoprotein
Glycophorin
Glycophorin receptors
provide acces for various infectious agents including plasmodium falciparum
Glycophorins
carry a number of blood group antigens
Major anion exchanger in cell membrane
Band 3
Peripheral protiens are
Transiently binding proteins that attach either to integral proteins or membrane itself
Spectrin has how many subunits
- alpha and beta
Spectrin binds the following proteins
Protein 4.1
Ankyrin
Actin
Function of spectrin
Maintains cellular shape
Structural support
Function of ankyrin
Provides primary linkage between membrane skeleton via spectrin binding
Provided primary linkage between lipid bilayer via band 3
Abnormalities of ankyrin produces
Hereditary spherocytosis
Protein 4.1 function
Links spectrin actin membrane skeleton to lipid bilayer
Protein 4.2 function
Stabilizes spectrin -actin - ankyrin association with band 3
in membrane organization; vertical interactions
stabilize lipid bilayer
in membrane organization horizontal interactions
maintain structure of cell membrane and gives it a high tensile strength
Defects in red cell membrane leading to hemolytic anemia
hereditary spherocytosis
hereditary elliptocytosis
hereditary pyropoikilocytosis
What is hereditary spherocytosis
A membrane defect that makes RBC spherical with increased osmotic fragility
What sex is affected most by hereditary spherocytosis
Both sexes affected equally
What membrane protein deficiency causes hereditary spherocytosis
Ankyrin, spectrin, protein 4.2
Also proteins involved in vertical interactions
Pathophysiology of hereditary spherocytosis
Defects in proteins involved in vertical interactions between membrane skeleton and lipid bilayer—>release of parts of lipid bilayer not supported by membrane skeleton—>Become spherical and less flexible—>difficult to pass through splenic microcirculation—>slowly passes through splenic microcirculation–>Ample time is gotten in this environment of low pH and glucose to break it down
potassium and water levels in hereditary spherocytosis
diminished
Clinical features of hereditary spherocytosis
Late detection
Symptoms of anemia is slight, Hb doesnt fall below 7.5g/dl
Jaundice
Splenomegaly
Gall stones
Leg ulcers
Aplastic anemia precipitated by parvovirus
Lab findings for hereditary spherocytosis
Aneamia Numerous spherocytes with no area of central pallor and decreased diameter high MCHC high osmotic fragility Mean cell fragility greater than 0.45 high reticulocyte count
Management of hereditary spherocytosis
folic acid
Splenectomy if severe
Hereditary spherocytosis common in
people of North European descent
Hereditary elliptocytosis common in
People of african and mediterranean descentdescent
Hereditary elliptocytosis confers resistance to this disease
Malaria
People with Hereditary elliptocytosis usually present as
Asymptomatic or with severe life threatening situation
Method of inheritance of hereditary elliptocytosis
Autosomal dominant
is hereditary spherocytosis milder than hereditary elliptocytosis
no. less cases of splenectomy recorded in elliptocytosis
Defects in what interactions cause hereditary elliptocytosis
horizontal interactions
Management of hereditary elliptocytosis
Because its usually mild, its asymptomatic and detected accidentally.
Those with severe symptoms can however undergo splenectomy or blood transfusions
Hereditary pyropoikilocytosis is seen in these patients
burn patients
