2) RBC structure Flashcards
3 main parts of RBC essential for survival and function
- membrane
- hemoglobin
- metabolic pathways
3 layers of RBC membrane and components
- outer layer —glycolipids, glycoproteins, proteins
- central layer —proteins, cholesterol, phospholipids
- inner layer —proteins
chemical composition of RBC membrane
40% lipids
52% proteins
8% carbs
used to separate RBC membane proteins
SDS polyacrilamide gel electrophoresis (SDS-PAGE)
examples of integral proteins
- glycophorins A, B, C
- Band 3
most important integral protein
glycophorin A
2 functions of band 3
- anion exchange channel
- anchors cytoskeleton to the lipid bilayer
functions of glycophorins (3)
- accounts for membrane sialic acid, giving RBCs a negative charge (repels others)
- location of many antigens
- anchors cytoskeleton to bilayer
examples of peripheral proteins
- spectrin
- ankyrin
- adducin
- band 4.1
- band 4.2
- actin
most abundant peripheral protein
spectrin
structure of spectrin
helix of two polypeptide chains (α,β)
They form dimers which link with other αβ chains to form tetramers.
The chains bind with other peripheral proteins to form a skeletal network that creates the “cytoskeleton”.
acts like a strong spring, giving membrane deformability
spectrin
functions of the cytoskeleton
- strengthens membrane
- protects cell from shear forces
- controls shape and deformability
tie network of cytoskeleton together
the 2 spectrin complexes
require energy to stay together
critical to RBC survival as it passes through vessels, and for O2 delivery
deformability
2 causes of ↓ deformability
- loss of ATP; ↓ phosphorylation of spectrin
- deposits of Ca2+; ↑ membrane rigidity
extravascular sequestration
spleen function
cells are squeezed through small sinusoidal orifices, and removed or fragmented
passively transported across RBC membrane
- H2O
- anions (Cl and HCO3)
travel through band 3
actively transported across RBC membrane
Na+ and K+
intracellular:extracellular ratios for Na and K
Na—1:12
K—25:1
Na-K pumps prevent ——- hemolysis
osmotic
3 RBC membrane lipids
- phospholipids
- glycolipids
- cholesterol
Changes in body lipid transport and metabolism may cause abnormalities in —————– that may alter RBC membrane composition.
plasma phospholipid concentration
interact with many glycoproteins to form antigens
glycolipids
RBC cholesterol is in continual exchange with…
unesterified plasma cholesterol
RBC morphology abnormality
proportional ↑ phospholipid & ↑ cholesterol in membrane
target cells
RBC morphology abnormality
abetalipoproteinemia with cholesterol accumulation in membrane (↑chol:PL ratio)
acanthocytes
↓ LCAT (lecithin cholesterol acyltransferase)
schistocytes & target cells
RBC morphology abnormality
↓ phosphorylated or altered spectrin
bite cells & spherocytes
RBCs are —–% Hgb
34%
Hgb is produced in…
65% in nRBCs
35% in reticulocytes (last stage in which hgb is made)
structure of hgb
- 4 heme groups (4 Fe + 4 protoporphyrin IX rings)
- 4 globin chains
carries Fe to young RBC
transferrin
after Fe is added, it goes to the ———– for insertion in to the protoporphyrin ring
mitochondria
major sites of heme synthesis
- young RBCs of marrow
- hepatocytes
ALA term
aminolevulinic acid
byproducts of heme synthesis that do not produce heme
uroporphyrinogen I
coproporphyrinogen I
lab tests measure ——— rather than unstable ———
porphyrins
porphyrinogens
only type —– isomers of porphyrins form heme
III
vitamin required for heme synthesis
Vit B6
In conditions with ineffective utilization of protoporphyrin, there are ↑ amounts of…
free erythrocyte protoporphyrins (FEPs)
lead inhibits…
ALA dehydrase
ferrochelatase
porphyria
defect in porphyrin synthesis, especially inherited
most common secondary porphyria
lead poisoning
ways to classify primary porphyrias
- organ —hepatic vs erythropoietic
- symptoms —neurological or cutaneous
neurological porphyrias
- acute intermittent porphyria
mixed porphyrias
- variegate porphyria
- hereditary coproporphyria
cutaneous porphyrias
- porphyria cutanea tarda
- congenital erythropoietic porphyria
- erythropoietic protoporphyria
neurological porphyria sx
- acute attacks
- ↑ ALA and PBG in urine
- abd pain
- weakness
- nausea
- constipation
- perspiration
- HTN
- tachycardia
- motor dysfunction
- sensory loss
- mental disturbances
cutaneous porphyria sx
- photosensitivity
- characteristic skin lesions
- no ALA/PBG (no neuro sx)
congenital erythropoietic porphyria sx
- ↑ uro I and copro I (feces, RBCs)
- splenomegaly
- brown pigment to teeth; fluoresces
- blistering
- pink urine
enzyme defect of PBG deaminase
acute intermittent porphyria
enzyme defect of protoporphyrin oxidase
variegate porphyria
enzyme defect of coproporphyrinogen oxidase
hereditary coproporphyria
enzyme defect of uroporphyrinogen decarboxylase
porphyria cutanea tarda
enzyme defect of ferrochelatase
erythropoietic protoporphyria
enzyme defect of uroporphyrinogen III cosynthase
congenital erythropoietic porphyria
↑ ALA in urine
↑ PBG in urine
acute intermittent porphyria
↑ ALA, PBG in urine
↑ proto in feces
↑ copro in feces
variegate porphyria
↑ ALA, PBG during attacks
↑ copro in feces
hereditary coproporphyria
↑ uro
↑ copro isomer I
porphyria cutanea tarda
↑ proto in RBC and feces
↑ FEP
erythropoietic protoporphyria
↑ uro I
↑ copro I
congenital erythropoietic porphyria
king george
variegate porphyria
most common porphyria
porphyria cutanea tarda
- —— and —— are water soluble so appear in urine.
- —— may be found in urine or feces.
- —— is found only in feces.
PBG and uro
copro
proto
globin chain production takes place in…
ribosomes in cytoplasm of nRBCs and retics
globin chains on chromosome 16 and 11
16: zeta, alpha
11: beta, gamma, delta, epsilon
3 types of normal adult hgb, structure, prevalence
- Hgb A—2𝛼, 2β—97%
- Hgb A2—2𝛼, 2δ—3.5%
- Hgb F—2𝛼, 2𝛾—<1%
we differentiate types of hgb by…
hgb electrophoresis
Fe in each heme is ———–; binding sites:
hexacovalent
4 —binding N of protoporphyrin
1 —binding histadine in globin
1 —reversibly binding O2
Fe in hemoglobin
Fe in methemoglobin
ferrous (Fe2+)
ferric (Fe3+) — no value in respiration
globins and protoporphyrins won’t accumulate without one another, but —– will, causing…
iron
organ damage
pappenheimers (ferritin aggregates)
siderocytes/sideroblasts
ringed sideroblasts
how does hemoglobin production change through gestation and infancy?
<3 months: Gower and Portland hgb (𝛇 and 𝛆)
Hgb F replaces these
20th week—β production begins
Birth—mostly Hgb F, some Hgb A
6 months—<8% Hgb F
1 year—<2% Hgb F
target cells
rate limiting step for heme synthesis
influenced by EPO
1) glycine and succinyl CoA to δALA
acanthocytes
schistocytes
