Haematology- Red blood cells Flashcards

1
Q

Describe the structure of a red blood cell

A

Biconcave
8 microns diameter but pass through 3 microns capillaries

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2
Q

What is the composition of the red cell membrane?

A
  • 50% proteins
  • 40% lipids
  • 10% carbohydrates
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3
Q

Describe the structure of the red blood cell membrane

A

Semi- permeable lipid bilayer, with proteins scattered throughout
Has:
- An outer hydrophilic layer
- Central hydrophobic layer
- Inner hydrophilic layer

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4
Q

What is the outer hydrophilic layer composed of?

A

Glycolipids, glycoproteins, and proteins

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5
Q

What does the central hydrophobic layer contain?

A

Proteins, cholesterol and phospholipids

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6
Q

What does the inner hydrophobic layer contain?

A

Mesh-like cytoskeletal proteins to support lipid bilayer

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7
Q

Describe the lipid composition of the red blood cell membrane

A
  • Phospholipids - 60%
  • Cholesterol- 30% - unesterfied free cholesterol between 2 layers
  • Sphingoloids - 10%
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8
Q

The distribution of phospholipids is asymmetrical. What are the uncharged phospholipids in the outer layer?

A
  • Phosphatidyl choline (PC)
  • Sphingomyelin (SM)
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9
Q

What are the charged phospholipids in the inner layer?

A
  • Phosphatidyl ethanolamine (PE)
  • Phosphatidyl serine (PS)
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10
Q

What 2 types of proteins are in the red blood cell membrane?

A
  1. Integral membrane proteins - traverse entire lipid bilayer membrane
    2- Peripheral proteins- limited to cytoplasmic surface of membrane and forms RBC cytoskeleton
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11
Q

What are the 2 major integral proteins?

A
  • Glycophorins
  • Band 3
    These are anion transporters
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12
Q

What does the cytoskeleton do for a RBC?

A

Acts as a tough framework to support the bilayer, and is responsible for deformability (ability of a material to change its shape or size under influence) and maintaining its biconcave shape.

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13
Q

What are the 4 major peripheral proteins?

A

-Spectrin
-Ankyrin
-Protein 4.1
-Actin

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14
Q

Describe spectrin

A

Most abundant of peripheral proteins, composed of alpha + beta chains.

Very important in RBC membrane integrity, binds with other peripheral proteins to form cytoskeletal network of microfilaments, responsible for biconcave shaped of RBC

If this becomes denatured, red cells become spherical and lose flexibility

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15
Q

Describe Ankyrin

A

Family of adaptor protein, interacts with band 3 and spectrin to achieve linkage between bilayer and cytoskeleton

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16
Q

Describe protein 4.1

A

Major structural element- links cytoskeleton to membrane by means of its associations with glycophorin and stabilises interaction of spectrin with actin

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17
Q

Describe Actin

A

Abundant protein in cell membrane- responsible for contraction and relaxation of membrane. Allows movement of cell surface enabling cells to migrate, engulf particles and divide.

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18
Q

Where are the carbohydrates on the RBC membrane?

A

Only on the external surface, attached to proteins and lipids

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19
Q

How do carbohydrates attach to proteins and lipids?

A

By a process called glycosylation

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20
Q

What does the carbohydrate do for a red blood cell?

A

Gives the cell identity, the distinguishing factor for human blood types (you know A, B, O, AB), they are what give the blood a group

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21
Q

Where are blood group antigens found?

A

On red cell membrane and these determine our blood group.

Many antigens are proteins e.g. Rhesus , and these proteins give other info to the red blood cell

Other antigens are carbohydrates e.g. ABO

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22
Q

Describe the structure of Haemoglobin

A

Globular protein that contains:

  • Haemoproteins
  • Haem
  • Iron
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23
Q

What are haemoproteins?

A

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

24
Q

What is haem a complex of?

A

A complex of protoporphyrin (IX) and ferrous iron (Fe2+)

25
Q

Where is iron in red blood cells?

A

Iron is held in the centre of haem molecules by bonds to 4 nitrogen of a porphyrin ring (this is a biochemical molecule bound to nitrogen)

26
Q

What is the main function of haemoglobin?

A
  • To carry oxygen to tissues and return carbon dioxide from tissues
27
Q

What is the ratio of Hb molecules to number of binding oxygen?

A

1 Hb molecule binds to 4 O2 molecules

28
Q

What is the most abundant Hb composition of adult Hb?

A

2 alpha haem groups and 2 beta haem groups.

This accounts for 96-98% of Hb in blood when in the normal range

29
Q

What is the less abundant composition of Hb in adult Hb 2? Also known as Hb A2

A
  • Hb is made of 2 alpha haem groups and 2 delta haem groups
  • This accounts for 1.5-3.2% of Hb in blood when in the normal range
30
Q

What is the composition of foetal hameoglobin (HbF)?

A
  • Hb F has 2 alpha haem groups and 2 gamma haem groups.
  • This accounts for 0.5-0.8% of Hb in blood when in the normal membrane
31
Q

How does membrane cholesterol exist in the red cell membrane?

A

In free equilibrium with plasma cholesterol

32
Q

What happens if there is an increase in free plasma cholesterol in the RBC membrane?

A
  • Results in an accumulation of cholesterol in RBC membrane
33
Q

What happens to the structure of the RBC membrane when there’s increased cholesterol?

A
  • They become acanthocytes- these are dense, shrunken, and irregularly shaped red blood cells with spikes on the outside.
34
Q

What are target cells (codocytes)?

A

Erythrocytes (RBC) with an increased cell membrane:volume ratio

They look like a target, as in a target for shooting arrows.

35
Q

What causes target cells (codocytes) ?

A

An increase in cholesterol and phospholipid is a cause of target cells.

They can also result from a decrease in intracellular haemoglobin

36
Q

Describe hereditary spherocytosis and how it causes damage to the cell membrane

A

-An inherited blood disorder in which red blood cells are very round and have trouble changing their shape.

This makes moving through small blood vessels difficult, therefore the red blood cells stay in the spleen longer, causing harm to the cells’ membrane.

37
Q

What are the causes of spherocytosis?

A
  • Ankyrin deficiency or abnormalities
  • Alpha or beta deficiency or abnormalities
  • Protein 4.2 abnormalities
  • Band 3 protein abnormalities
38
Q

Describe hereditary elliptocytosis?

A
  • Red blood cells are elliptically shaped (elongated, oval shape). These can be called elliptocytes.
  • The spleen captures and eliminates these abnormal elliptocytes, resulting in hemolytic anemia (this is when the red blood cells are being destroyed faster than they’re being produced.
39
Q

What are haemoglobinopathies?

A

Medical term for a group of inherited blood disorders involving Hb

40
Q

What are 2 haemoglobinopathies?

A

1- Thalassaemias - results in no production or too little production of haemoglobin, causing anaemia
2- Sickle cell disease- Hb is abnormal shape, resulting in RBC to be rigid and shaped like a ‘C’ or sickle

41
Q

What is microcytosis?

A

Presence in blood of significant numbers of erythrocytes that are SMALLER than normal

42
Q

What is macrocytosis?

A

Condition where red blood cells are LARGER than normal

43
Q

What is anisocytosis?

A

Presence of red blood cells of VARYING SIZES

44
Q

What is poikilocytosis?

A

Presence of red blood cells of VARYING SHAPES

45
Q

How do red blood cells generate energy?

A

Through anaerobic oxidation of glucose via glycolysis via the glycolytic pathway

46
Q

What other way can red blood cells produce energy?

A

Via the hexose monophosphate shunt (HMS) (or can be called pentose phosphate pathway)

47
Q

Why must red blood cells generate ATP?

A
  • To survive the 120 days it needs to live
  • To maintain red cell shape and deformability
  • To regulate intracellular cation conc. via cation pumps (Na/K pump)
48
Q

What are disorders of the glycolytic pathway and what is the result of this?

A
  • Pyruvate Kinase (PK) deficiency
  • ATP is depleted, cells lose large amount of potassium and water, become dehydrated and rigid
  • This causes chronic, non-spherocytic haemolytic anaemia.
49
Q

What does NADPH do?

A
  • Protects the RBC from oxidative damage, maintains glutathione (a redox active, small molecule critical to cellular and organism health) in reduced state (GSH)
50
Q

What are disorders of HMS and what are the results of this?

A
  • Generation of NADPH and GSH impaired
  • This causes acute haemolysis on exposure to oxidant stress- oxidative drugs, fava (broad) beans or infections.
  • Hb precipitation- Heinz bodies- This occurs from oxidative injury resulting in denatured (oxidised), precipitated haemoglobin that tends to adher to the inner surface of RBC membranes.
  • G6PD deficiency- this is the most common enzymopathy (genetic disorders affecting cellular metabolism). This deficiency means the body doesn’t have enough G6PD enzyme, so red blood cells break down faster than they usually would, resulting in haemolytic anemia.
51
Q

What is meant by precipitation?

A

A process where soluble antigens bind with their specific antibody, resulting in the formation of an insoluble precipitate.

52
Q

How does the lipid bilayer binding to the cytoskeleton help a RBC?

A
  • Helps maintain flexible biconcave shape with ability to deform
  • Biconcave shape also provides optimum SA:V ratio for gas exchange
53
Q

How does having proteins traverse throughout the lipid bilayer benefit RBC?

A

These proteins serve as transports of anions, water and glucose

54
Q

How does the RBC having no nucleus or mitochondria and just having Hb benefit it?

A
  • Hb allows the RBC to perform its primary function:

Bind to O2 to form oxyhaemoglobin and transport oxygen from lungs to tissues

Binds to CO2 to form carbominohaemoglobin (HbCO2) and transport carbon dioxide from tissues

55
Q

What are the purposes of the 2 main metabolic pathways of the blood?

A
  • Generates ATP to maintain intracellular cation concentration and cell shape
  • NADPH and GSH to protect against stress and Hb precipitation