5M RBCs

4,000-11,000 WBCs

150,000-400,000 platelets per microliter human blood

Human RBC disk diameter?

Human RBC thickness?

Volume normally vs. abnormally?

6-8 μL (microliter)

2 μL

90 fL (femtoliter=10-15L) vs. 150 fL

Function: travel the small capillaries repeatedly during its ___ day lifespan.

Structure: ?

120 day lifespan. That was easy :)

1. Highly elastic

2. Responds rapidly to applied stresses

3. Capable of undergoing large membrane extensions without fragmentation

1. Removes old red blood cells

2. Holds a reserve of blood in case of hemorrhagic shock

3. Recycles iron

4. Analagous to a large lymph node, as its absence leads to a predisposition toward certain infections

(wikipedia)

RBC Function: respiration, the delivery of oxygen from the lungs to tissues and the removal of CO2

Structure: ?

Flexibility

Durability

Nutrient Exchange for Glycolysis (Glucose transporter 1: GLUT1)

Control of ionic environment and hydration (Anion exchange: Cl^-, HCO₃) (Cation exchange: Na⁺, K⁺, Ca⁺⁺)

Signaling

Structure: biconcave disk, discoid shape

Function: ?

1. Less rotation, promotes laminar flow in larger vessels with cell-free zone at endothelium

2. When flowing in microvessels, the flexible RBCs migrate toward the vessel central region, resulting in a RBC concentrated core in the center, and a cell free layer (CFL) is developed near the vessel wall.

1. the deformability of the cells

2. their hydrodynamic interactions

3. thermally induced cell membrane undulations

1. disordered biconcave-disk shapes

2. parachute-shaped RBCs aligned in a single file

3. slipper-shaped RBCs arranged as 2 parallel interdigitated rows

Asymmetrically.

Phosphatidyl choline and Sphingomeyelin are predominantly in the outer monolayer.

Most Phosphatidylethanoloamine and all Phosphatidyl serine and Phosphoinositides are located in the inner monolayer

Translocation of which phospholipid to which monolayer leads to recognition and phagocytosis which plays a role in the normal removal of senescent erythrocytes?

In which pathologies does this play a roll?

Translocation of Phosphotidyl serine to the outer monolayer.

Sickle cell anemia and thalassemias.

HE more common where?

Clinical expression?

More common in malaria endemic regions.

Clinically heterogenious: asymptomatic carriers (majority) to severe life-threatening anemia (10%)

Each spectrin heterodimer consists of two antiparallel, loosely intertwined, flexible polypeptide chains (alpha and Beta)

alpha and Beta chains are composed of repeating domains 106 aa long

Attached noncovalently to each other at multiple points, including both ends

Two dimers associate to form a tetramer at the phophorylated "head" end

Spectrin

Protein 4.1R

Actin

Adducin

Tropomyosin

Tropomodulin

alpha spectrin: 65%

Beta spectrin: 30%

Protein 4.1: 5%

Band 1: alpha spectrin --- heaviest

Band 2: Beta Spectrin

Band 2.3: Ankyrin

Band 3: Band 3 (AE1)

Band 4.1: Protein 4.1 --- lightest

Glycophorins heavily glycosylated sialoglycoproteins, homodimers which run on SDS anomalously due to high negatively charged carbohydrate content

Disorder of vertical interactions between spectrin skeleton and lipid bilayer.

Loss of membrane with resultant shape change. If unable to traverse spleen, then removed. Severity of disease directly related to extent of membrane surface area loss

Racial prevalence of HS:

Typical clinical presentation:

HS occurs in all racial groups, particularly common in N European ancestry (1 in 2000 to 3000)

Hemolysis with anemia

Jaundice

Reticulocytosis

Gallstones

Splenomegaly

HS genotype/phenotype correlations

As well as mutation frequencies

75% dominant; 25% recessive

Ankryin HS most common (50-60%), severity varies

(Proportional and secondary decrease in spectrin assembly on membrane in spite of normal synthesis)

Beta spectrin HS (20%)

Band 3 HS (15-20%) pincered or mushroom spherocytes

alpha spectrin HS (Severe, Autosomal Recessive)

Protein 4.2 (<5%)

Rh Complex (<1%)

No defect identified (10%)

(Spectrin self-association site)

Beta spectrin

Ankyrin

Band 3 (involved in linkages between the spectrin skeleton and the lipid bilayer in both Ankyrin and Junctional (Protein 4.1) Complexes

Glycophorin A

Protein 4.2

(Protein 4.1R)

Spectrin/Actin

Protein 4.1R

Band 3

Glycophorin C

Adducin/Tropomyosin/Tropomodulin

Glut1

Major integral membrane protein in RBC

Anion exchange activity, transporting bicarbonate ions out of the RBC in exchange for Chloride ions

Hydrophobic cytoplasmic domain binds to intracellular proteins: hemoglobin, enzymes

Band 3 exists as oligomers: 60% dimers, 40% tetramers.

Band 3 deletion associated with membrane rigidity

-SAO very common in malaria endemic areas of Melanesia, Malaysia, Philippines, Indonesia and Southern Thailand

-5-25% prevalence in endemic areas

-Dominant; only heterozygotes have been identified in high prevalent regions, implying homozygosity may lead to embryonic lethality.

-Very rigid membrane and mechanically more stable

-No or minimal hemolysis

-Only one mutation identified: genomic deletion of 27 bp encoding AA 400-408 located at the boundary of the cytoplamsic and first transmembrane domain of Band 3

Defect in hydration status of erythrocyte.

Large number of membrane proteins play a role in cation homeostasis and normal cell water content. Hereditary stomatocytosis describes a wide spectrum of autosomal dominant hemolytic disorders in which the basal RBC membrane cation permeability is increased.

Hereditary Stomatocytosis

Cryohydrocytosis form

Hereditary Stomatocytosis:

Overhydrated hereditary stomatocytosis

Dehydrated hereditary stomatocytosis

RhAG mutation

Most common

Well compensated anemia

Genetic basis unknown

ABO : Carbohydrate antigens on H protein

Rh/RhAG : erythroid specific

12 transmembrane helices

CO₂ and/or NH₃ transporter

Duffy: receptor for plasmodium vivax (malaria)

Diego: on Band 3

vertical interactions

horizontal interactions

in the rbc plasma membrane

Vertical interactions connect the red cell cytoskeleton via linker proteins (ankyrin and protein 4.1R) to integral membrane proteins (Band 3 and plycophorin C). Mutations in any of these components gives rise to spherocytosis.

Horizontal interactions between members of the cytoskeleton network (Mainly spectrins) result in elliptocytosis. Forget about cohesion.