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Pathology 1 > RBC Structure & Function > Flashcards

RBC Structure & Function Flashcards

1
Q

How are RBCs able to transport respiratory gases to/from tissues?

A

RBCs are capable of traversing the microvascular system without mechanical damage and retain a shape
RBC membrane is highly flexible yet tough

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2
Q

What is the role of cholesterol in the membrane?

A

Cholesterol won’t form its own membrane so inserts itself into bilayer with with its polar hydroxyl group close to the phospholipid head
membrane [cholesterol] determines membrane SA and fluidity
Increased choleterol = decreased deformability

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3
Q

What is the consequence of excess plasma cholesterol?

A

Incorporates preferrentially in outer leaflet of RBC membranes

  • RBC becomes less deformable
  • Remodelled when passing through spleen
  • Forms acanthocytes
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4
Q

What determines the membranes strength?

A

Interactons between membrane and cytoskeletal proteins determine strength and flexibility

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5
Q

What do experiments on humans and rats with liver disease show?

A

Changes in rbc shape => forms alterations in membrane lipid content
Secondary to plasma lipids changes
Production of abnormal lipoproteins causes increase in [free cholesterol] occur in various types of liver diseases

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6
Q

Where in the membrane are integral membrane proteins?

A

Extend from outer surface to and traverse entire membrane to inner surface

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7
Q

Describe the structure of RBC membranes

A
  • Semi permeable lipid bilayer with proteins throughout
  • Outer hydrophilic porion composed of glycoproteins,
    glycolipids, and proteins
  • Central hydrophobic layer containing proteins,
    cholesterol and phospholipids
  • inner hydrophilic layer of meshlike cytoskeletal proteins
    supporting lipid bilayer
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8
Q

How do congenital abnormalities arise in lipid composition?

A

Increased cholesterol causes acanthocytes which increases blood cholesterol and phospholipids causing target cells

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9
Q

Name the uncharged phospholipids on the outer membrane layer

A

Phosphatidyl Choline, sphingomyelin and glycolipids

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10
Q

How does the RBCs geometry enable it to withstand structural deterioration?

A

(SA:Vol) facillitates deformation whilst maintaining a constant SA

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11
Q

What is the composition of red cell membrane?

A

50% - proteins
40% - lipids
10% - carbohydrates

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12
Q

What are the 2 major integral membrane proteins?

A

Glycophorins - A,B and C
Band 3 - anion transporter

(other: Na+/K+ ATPase, Aquaporin 1, Surface Receptors e.g. TKAK)

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13
Q

What is the consequence of increased cholesterol in RBCs?

A

Appear distorted (acanthocytosis) caused by target cells

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14
Q

How is the membranes deformability not cause structural damage to RBC?

A

Spectrin molecules undergo conformational changes

Some are uncoiled and extended others are compressed and folded

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15
Q

What are the charged phospholipids of the inner layer?

A

Phosphatidylethanolamine, phosphatidylserine and phosphotidylinositol

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16
Q

How is cholesterol distributed throughout the cell?

A

Membrane cholesterol exists in free equilibrium with plasma cholesterol
Increasing free plasma cholesterol causes accumulation of cholesterol in RBC membrane

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17
Q

What is the primary function of RBCs?

A

Transport of respiratory gases to and from tissues

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18
Q

Describe the sturcture and function of Spectrin

A

Most abundant peripheral protein
composed of α and β chains
RBC membrane integrity - binds with other peripheral proteins to form microfilaments
Controls biconcave shape and deformability

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19
Q

What is the function of glycolipids on cell membranes?

A

Glycolipids maintain cell membrane stability and facilitate intracellular recognition
Crucial for immune system and connections allowing cells to connect and form tissues

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20
Q

What is the purpose of RBC biconcave shape?

A

Maximises SA to increase efficiency of oxygen absorption

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21
Q

What is the significnce of microfilaments to RBC structure?

A

Microfilaments strengthen the membrane protecting it from breaking

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22
Q

What is the significance of maintaining asymmetric distribution of phospholipids in the red cell membrane?

A

Localisation of PS and phosphoionositides to the inner monolayer has several functional implications
- macrophages recognise & phagocytose red cells
exposing PS on their outer surface

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23
Q

How does the SA:vol effect membrane deformability?

A

High SA:Vol facilitates large reversible elastic deformation of the RBC allowing it to repeatedly pass through 3um capillaries during microcirculation

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24
Q

How does spectrin interact with other proteins?

A

Spectrin must be phosphorylated by Protein Kinase requiring ATP
- [ATP] decreases; decreased phosphorylation of spectrin

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25
What is the percentage composition of lipids?
60% - phospholipids 30% - natural lipids (cholesterol) 10% - glycolipids
26
What is the role of glycophorins?
Account fpr location of RBC antigens Import negative charge to cell Reduce interaction with other cells / endothelium
27
What factors affect the RBC membranes deformability?
1. Cytoplasmic viscosity 2. Intracellular debris 3. Membrane rigidity 4. SA:Vol ratio
28
What are glycolipids?
Lipids with carbohydrates attached via a covalent glycosidic bond
29
What happens to unphosphorylated spectrin in cell membranes?
Unphosphorylated spectrin no longer binds to actin Membrane isn't as elastic Loss in deformability Decreased RBC survival time
30
What is the purpose of localisation of PS on inner layer of red cell membranes?
``` Keeping PS on inner layer allows cells to survive the frequent encounters with macrophages of the reticuloendothelial system (esp. in the spleen) ```
31
What is the consequence of mutations in peripheral proteins?
Mutations in cytoskeletal proteins Spectrin and Protein 4.1 weakens horizontal linkage decreasing membrane mechanical stability causing hereditary eliptocytosis (He)
32
What are the RBCs membrane functions?
- Maintain cell volume - Maintain Na+/K+ content - Maintain osmotic fragility - Ca2+ homeostasis - Anion exchange
33
What is the role of Actin?
Contraction and relaxation of membrane Strong cohesion between bilayer and membrane Skeleton maintains surface area
34
Name some of the major peripheral proteins
Spectrin, Ankyrin, Protein 4.1, Actin
35
What is the link between RBC membrane and its structure
They have a flexible membrane with a high SA:Vol
36
What is the function of red cell membranes?
Provides shape - Provides optimum SA:Vol ratio for respiratory exchange Provides deformability / elasticity - Allows passage through microvessels Regulates intracellular cation concentration
37
What is the specific function of Protein 4.1?
Links cytoskeleton to membrane by means of its associations with glycoproteins Stabilises Spectrin and Actin interaction
38
What are glycophorins?
All glycophorins are recptors or transport proteins | 3 types: A, B and C
39
What is the consequence of abnormalities in peripheral proteins?
Defects of Band 3, Ankyrin or Protein 4.1 leads to destabilisation of overlying lipid bilayer and release of lipid in microvessels causing: Hereditary ellipocytosis Hereditary Spherocystosis
40
Describe the structure of red blood cells
``` Contain no nucleus, mitochondria or endoplasmic reticulum Biconcave shape (8um) Able to deform and pass through 3um capillaries or reticuloendothelial system without fragmentation ```
41
How does the cytoplasmic viscosity regulate RBC structure?
Determined by MCHC - as MCHC rises, viscosity rises exponentially
42
What are peripheral proteins?
Proteins limited to the cytoplasmic surface of the membrane forming the RBC cytoskeleton
43
How does an increase in plasma cholesterol effect membrane cholesterol?
An increaes in plasma cholesterol causes an increase in membrane cholesterol => leads to Acanthocytes
44
What is the role of Band 3?
Acts as an anion transporter channel | Links lipid bilayer to underlying membrane cytoskeleton (ankyrin)
45
Describe the Pentose Phosphate Pathway
Alternative to glycolysis Generates NADPH and pentoses NADPH maintains gultathione in reduced form (GSH) RBC uses GSH to protect itself from oxidative damage
46
What is haemoglobin?
Hb is a globular protein
47
What is the role of Peripheral proteins?
- Provide rigid support & stability to bilayer - Deformability properties for RBC - Leads to shape change
48
What is a prosthetic group?
The non protein components of a conjugated protein
49
What does metabolism provide energy for?
- Cation pumps maintenance - Hb maintenance in reduced state - Reduced sulphydryl and other proteins in Hb maintenance - RBC integrity and deformability maintenance
50
What are haemoproteins?
A group of specialised proteins that contain a haem group tightly bound as a prosthetic group
51
What is the structure of Haemoglobin?
Made of 4 polypeptide chains | 2 α globin chanis and 2 β chains
52
What is the structure of haem?
Haem is a complex of Protoporphyrin IX and Ferrous Iron Fe2+ | Iron is held in the centre of haem molecules by bonds to the 4 nitrogens of the porphyrin ring
53
What is the Leubering Rapoport Shunt?
A biochemical pathway in mature erythrocytes involving the formation of 2,3-DPG
54
What is the fnction of 2,3-DPG?
Essential for maintaining normal oxygen tension, regulating HB affinity - regulates oxygen release from Hb and delivery to tissues
55
What is the role of the Hexose monophosphate shunt?
Used for NADPH production from NADP
56
What happens to the methaemoglobin reductase pathway in the absence of the methaemoglobin reductase enzyme?
Methaemoglobin accumulates and can't carry oxygen
57
List 2 integral proteins in red cell membranes
- Glycophorins | - Band 3
58
What are the key metabolic pathways for RBCs?
Glycolytic Pathway Hexose Monophosphate Shunt Methaemoglobin Reductase Pathway Luebering Rapoport Shunt
59
Describe the methaemoglobin reductase pathway
Membrane Na+/K+ ATPase used Produces NADPH needed by methaemoglobin reductase enzyme Maintains iron in Ferrous state
60
Describe the glycolytic pathway?
1. Glucose metabolised in a series of reactions forming lactate 2. Generates 2 ATP for every 1 glucose molecule used Generates 90% of energy needed by RBCs ATP provides energy for maintenance of RBC cell volume, shape, flexibility and cation pumps

Pathology 1 (20 decks)

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