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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
Q

What is the percentage composition of lipids?

A

60% - phospholipids
30% - natural lipids (cholesterol)
10% - glycolipids

26
Q

What is the role of glycophorins?

A

Account fpr location of RBC antigens
Import negative charge to cell
Reduce interaction with other cells / endothelium

27
Q

What factors affect the RBC membranes deformability?

A
  1. Cytoplasmic viscosity
  2. Intracellular debris
  3. Membrane rigidity
  4. SA:Vol ratio
28
Q

What are glycolipids?

A

Lipids with carbohydrates attached via a covalent glycosidic bond

29
Q

What happens to unphosphorylated spectrin in cell membranes?

A

Unphosphorylated spectrin no longer binds to actin
Membrane isn’t as elastic
Loss in deformability
Decreased RBC survival time

30
Q

What is the purpose of localisation of PS on inner layer of red cell membranes?

A 
Keeping PS on inner layer allows cells to survive the frequent encounters with macrophages of the 
reticuloendothelial system (esp. in the spleen)
31
Q

What is the consequence of mutations in peripheral proteins?

A

Mutations in cytoskeletal proteins Spectrin and Protein 4.1 weakens horizontal linkage decreasing membrane mechanical stability causing hereditary eliptocytosis (He)

32
Q

What are the RBCs membrane functions?

A
  • Maintain cell volume
  • Maintain Na+/K+ content
  • Maintain osmotic fragility
  • Ca2+ homeostasis
  • Anion exchange
33
Q

What is the role of Actin?

A

Contraction and relaxation of membrane
Strong cohesion between bilayer and membrane
Skeleton maintains surface area

34
Q

Name some of the major peripheral proteins

A

Spectrin, Ankyrin, Protein 4.1, Actin

35
Q

What is the link between RBC membrane and its structure

A

They have a flexible membrane with a high SA:Vol

36
Q

What is the function of red cell membranes?

A

Provides shape
- Provides optimum SA:Vol ratio for respiratory exchange

Provides deformability / elasticity
- Allows passage through microvessels

Regulates intracellular cation concentration

37
Q

What is the specific function of Protein 4.1?

A

Links cytoskeleton to membrane by means of its associations with glycoproteins
Stabilises Spectrin and Actin interaction

38
Q

What are glycophorins?

A

All glycophorins are recptors or transport proteins

3 types: A, B and C

39
Q

What is the consequence of abnormalities in peripheral proteins?

A

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
Q

Describe the structure of red blood cells

A 
Contain no nucleus, mitochondria or endoplasmic reticulum 
Biconcave shape (8um)
Able to deform and pass through 3um capillaries or reticuloendothelial system without fragmentation
41
Q

How does the cytoplasmic viscosity regulate RBC structure?

A

Determined by MCHC - as MCHC rises, viscosity rises exponentially

42
Q

What are peripheral proteins?

A

Proteins limited to the cytoplasmic surface of the membrane forming the RBC cytoskeleton

43
Q

How does an increase in plasma cholesterol effect membrane cholesterol?

A

An increaes in plasma cholesterol causes an increase in membrane cholesterol
=> leads to Acanthocytes

44
Q

What is the role of Band 3?

A

Acts as an anion transporter channel

Links lipid bilayer to underlying membrane cytoskeleton (ankyrin)

45
Q

Describe the Pentose Phosphate Pathway

A

Alternative to glycolysis
Generates NADPH and pentoses
NADPH maintains gultathione in reduced form (GSH)
RBC uses GSH to protect itself from oxidative damage

46
Q

What is haemoglobin?

A

Hb is a globular protein

47
Q

What is the role of Peripheral proteins?

A
  • Provide rigid support & stability to bilayer
  • Deformability properties for RBC
  • Leads to shape change
48
Q

What is a prosthetic group?

A

The non protein components of a conjugated protein

49
Q

What does metabolism provide energy for?

A
  • Cation pumps maintenance
  • Hb maintenance in reduced state
  • Reduced sulphydryl and other proteins in Hb
    maintenance
  • RBC integrity and deformability maintenance
50
Q

What are haemoproteins?

A

A group of specialised proteins that contain a haem group tightly bound as a prosthetic group

51
Q

What is the structure of Haemoglobin?

A

Made of 4 polypeptide chains

2 α globin chanis and 2 β chains

52
Q

What is the structure of haem?

A

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
Q

What is the Leubering Rapoport Shunt?

A

A biochemical pathway in mature erythrocytes involving the formation of 2,3-DPG

54
Q

What is the fnction of 2,3-DPG?

A

Essential for maintaining normal oxygen tension, regulating HB affinity
- regulates oxygen release from Hb and delivery to
tissues

55
Q

What is the role of the Hexose monophosphate shunt?

A

Used for NADPH production from NADP

56
Q

What happens to the methaemoglobin reductase pathway in the absence of the methaemoglobin reductase enzyme?

A

Methaemoglobin accumulates and can’t carry oxygen

57
Q

List 2 integral proteins in red cell membranes

A
  • Glycophorins

- Band 3

58
Q

What are the key metabolic pathways for RBCs?

A

Glycolytic Pathway
Hexose Monophosphate Shunt
Methaemoglobin Reductase Pathway
Luebering Rapoport Shunt

59
Q

Describe the methaemoglobin reductase pathway

A

Membrane Na+/K+ ATPase used
Produces NADPH needed by methaemoglobin reductase enzyme
Maintains iron in Ferrous state

60
Q

Describe the glycolytic pathway?

A
  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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