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Intro to Med > The red blood cell:structure and function > Flashcards

The red blood cell:structure and function Flashcards

1
Q

In terms of structural properties how much of each component of the RBC is linked to the membrane?

A

-Consists of
-50% proteins
-40% lipids
-10% Carbohydrates

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2
Q

What is the structure of the red cell membrane?

A

-A semi-permeable lipid bilayer; with proteins scattered throughout

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3
Q

What are the outer, inner and central layers of the red cell membrane and what do they contain?

A

-An outer hydrophilic portion composed of glycolipids, glycoproteins and proteins
-A central hydrophobic layer containing proteins, cholesterol and phospholipids
-An inner hydrophilic layer of mesh-like cytoskeletal proteins to support lipid bilayer

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4
Q

What are the lipid components of red cell membrane and there percentages?

A

-Phospholipids-60%
-Cholesterol-30%
-Sphingolipids-10%

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5
Q

What is the distribution of lipids like in the red cell membrane?

A

-Distribution of phospholipid is asymmetric

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6
Q

Where are the uncharged and charged phospholipids located and what are they?

A

-Uncharged phospholipid of outer layer
-Phosphatidyl choline and Sphingomyelin
-Charged phospholipids of inner layer
-Phosphatidyl ethanolamine
-Phosphatidyl Serine

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7
Q

What is in between the the inner and outer layer of charged and uncharged phospholipids?

A

-Unesterified free cholesterol between

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8
Q

Where do integral membrane protein extend from and to where?

A

-Extend from outer surface and transverse entire lipid bilayer membrane to inner surface

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9
Q

What are the 2 major integral membrane proteins?

A

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

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10
Q

What do glycophorins A,B and C impact and what does this reduce?

A

-They impact -ve charge to cell, reducing interaction with other cells/endothelium

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11
Q

What are examples of other integral proteins in the cell membrane, other than the 2 major ones?

A

-Na+/K+ ATPase, Aquaporin 1, surface receptors like TfR

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12
Q

What are peripheral proteins of the red cell membrane limited to and what do they form?

A

-Limited to cytoplasmic surface of membrane and forms the RBC cytoskeleton

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13
Q

What does the RBC cytoskeleton act as?

A

-Cytoskeleton acts as tough framework to support bilayer, responsible for deformability and maintains biconcave shape

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14
Q

What are examples of major peripheral proteins with key roles within the RBC membrane?

A

-Spectrin, Ankyrin, Protein 4.1 and actin

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15
Q

What is the most abundant peripheral protein

A

Spectrin

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16
Q

What chains is spectrin composed of?

A

Composed of alpha and beta chains

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17
Q

What is spectrin important in RBC and how so?

A
  • Very important in RBC membrane integrity
    as it binds with other peripheral proteins to form the cytoskeletal network of microfilaments
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18
Q

What does spectrin control and why?

A
  • Controls biconcave shape and deformability of cell
    If denatured red cell becomes spherical, loses flexibility
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19
Q

What does ankyrin do and via what interactions?

A

-Primariy anchors lipid bilayer to membrane skeleton
-via interaction with spectrin and band 3

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20
Q

What does protein 4.1 link and what does this stabilise?

A

-May link the cytoskeleton to the membrane by means of its associations with glycophorin
-Stabilises interaction of spectrin with actin

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21
Q

What is actin responsible for?

A

-Responsible for contraction and relaxation of membrane

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22
Q

What maintains surface area of red blood cell?

A

-Strong cohesion between bilayer and membrane skeleton maintains surface area

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23
Q

Where do carbohydrates occur in red blood cell membrane?

A

-They occur only on the external surface of cell

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24
Q

By what process are carbohydrate groups attached to proteins and lipids?

A

The carbohydrate groups are attached to proteins and lipids by process call glycosylation.

25
Q

What do the carbohydrate groups attached to proteins give to the cell?

A

The carbohydrate gives a cell identity; the distinguishing factor for human blood types

26
Q

Where are blood group antigens found in the RBC and what do they determine?

A

-Are found on red cell membrane and determine our blood group

27
Q

What is the primary function of RBC and how is this achieved?

A

-Primary function of RBC is transport of respiratory gases to and from the tissues
-To achieve this:
-RBC traverse the microvascular system without mechanical damage and retain a shape which facilitates gaseous exchange

28
Q

Function of RBC in relation to its shape

A

-Provides the optimum surface area to volume ratio for respiratory exchange

29
Q

what does the RBC being elastic allow?

A

Allowing for passage through micro vessels

30
Q

What type of ion concentration does RBC regulate and how is this achieved?

A

-Regulates intracellular cation concentration
-Cation pumps allow water and electrolytes to exchange

31
Q

What impact will the RBC membrane have, if there is an increase in free plasma cholesterol? How does this make the RBC appear? Additionally, what is the consequence of increased cholesterol and phospholipids and what are the causes?

A

An increase in free plasma cholesterol results in an accumulation of cholesterol in the RBC membrane which reduces fluidity
-RBCs with increased cholesterol appear distorted resulting in the formation of acanthocytes
-Acanthocytes are RBCs with uneven spikey projections
Increase is cholesterol and phospholipids is a cause of target cells
-Target cells occur in disproportional increase in SA:V (abnormally high SA) - presented with cytoplasmic halo under Electron microscope
-Causes can be B-thalassaemia, IDA, SCA, sideroblastic anaemia, liver disease

32
Q

What can cause hereditary spherocytosis

A

-Ankyrin deficiency or abnormalities
-A or B spectrin deficiency or abnormalities
-Band 3 protein abnormalities
-Protein 4.2 abnormalities

33
Q

What can cause hereditary eliptocytosis?

A

-A or B spectrin mutation-defective spectrin dimer
-A or B spectrin mutation- defective spectrin-ankyrin association
-Protein 4.1 deficiency or abnormalities

34
Q

What type of protein is haemoglobin?

A

-Haemoglobin(Hb) is globular haemoprotein

35
Q

What are hemoproteins?

A

-Haemoproteins are group of specialized protein that contain haem as a tightly bound prosthetic group

36
Q

What is haem a complex of?

A

-haem is a complex of protoporphyrin IX and ferrous iron(Fe2+)

37
Q

Where is Iron held in haemoglobin?

A

-Iron held in the centre of haem molecule by bonds to the 4 nitrogen of a porphyrin ring

38
Q

What is the globin structure of haemoglobin?

A

-4 polypeptide subunits
-2 alpha globin chains
-2 beta globin chains

39
Q

What are the 2 categories of haemoglobinopathies?

A

-Inherited disorders of Hb; 2 categories
1. Thalaassaemias - reduced synthesis of globin chain (quantitative change)
2. Sickle cell disease - mutation in one of globin chain (valine instead of glutamic acid) gives rigid structure (qualitative change)

40
Q

What are the two sources of RBC energy? what are the two main enzymes?

A

-Hexose monophosphate shunt(HMS) or pentose phosphate pathway(PPP): Glucose-6-phosphodihydrogenase (G6PD)
-glycolytic pathway: pyruvate kinase (PK)

41
Q

Why does RBC have no oxidative phosphorylation and therefore how is energy synthesised? also list the functions of the main enzyme involved and a key product in the pathway?

A

-RBC has no DNA or RNA therefore no oxidative phosphorylation
-Therefore 10% of RBC glucose is via the HMS also known as PPP
-G6PD is involved in the PPP- helps maintain the shape of RBC; one of the products of this pathway is NADPH helps protect RBC from oxidative damage (its a common electron donor) by increasing the levels of GSH (glutathione) which is an antioxidant.

42
Q

What does GSH act as in oxidative phosphorylation?

A

-GSH acts as an antioxidant

43
Q

What does G6PD deficiency impair and cause?

A

-NADPH and GSH generation impaired
-Acute haemolysis on exposure to oxidant stress: oxidative drugs such as sulphonamides , (fava(broad) beans or infections
-causes Hb precipitation - Heinz bodies (denatured RBCs)

44
Q

What chromosome is G6PD deficiency linked with?

A

X-linked

45
Q

What drugs to patients with G6PD deficiency have to avoid?

A

-Patients with G6PD deficiency have to avoid particular oxidative drugs like sulphonamides, dapsone and quinone based anti malaria drugs

46
Q

What do patients with G6PD deficiency have protection against?

A

-G6PD deficiency patients have protection against severe malaria

47
Q

What does the glycolytic pathway, also known as embden meyerhof pathway, generate in RBC and what does it maintain and regulate?

A

-Generates energy in ATP:
-To maintain red cell shape and deformability
-To regulate intracellular cation concentration via Na/K pump

48
Q

What type of disorder is PK deficiency in the glycolytic pathway and what does it result in?

A

-PK deficiency is an autosomal recessive disorder
-Results in low intracellular ATP generation affecting membrane structure

49
Q

What is the ATP generated from the glycolytic pathway required for?

A

-ATP generated from this pathway is required for the RBC membrane pump in order to maintain red cell volume and high intracellular K+ levels. 3 Na+ out and 2 K+ in.

50
Q

What will a stop in glycolysis in RBC result in?

A

-A stop in glycolysis results in build up of glycolytic intermediates, include 2,3 biphosphoglycerate, which binds to and shifts the oxygen dissociation curve to the right

51
Q

What is depleted in Pyruvate kinase deficiency and what does this cause?

A

-ATP is depleted
-Cells lose large amount of potassium and water, becoming dehydrated and rigid
-Causes chronic non-spherocytic haemolytic anaemia

52
Q

What type of disease is pyruvate kinase deficiency?

A

Autosomal recessive

53
Q

When does non-spherocytic haemolytic anaemia worsen with PK deficient patients?

A

-non-spherocytic haemolytic anaemia may worsen at times of infection or other stress

54
Q

What may be seen on a blood film of patients suffering with pyruvate kinase deficiency?

A

-Dense red cells with spicules(prickle cells) may be seen on the peripheral blood film - acanthocytes from HA

55
Q

What are three features which allow RBC to withstand life without structural deformation and how?

A

-Geometry of cell; surface area to volume ratio
-Facilitates deformation whilst maintaining constant surface area
-Membrane deformability
-Spectrin molecules undergo reversible change in conformation: some uncoiled and extended, others compressed and folded
-Cytoplasmic viscosity determined by MCHC
-As MCHC rises, viscosity rises exponentially

56
Q

What is anisocytosis?

A

size variation of RBC (prominent in IDA - iron deficient anaemia)
-macrocytes
-microcytes

57
Q

What is poikilocytosis?

A

shape variation of RBC

58
Q

what is hypochromia?

A

lack of haem in RBC

59
Q

What does a normal RBC and target cell look like under microscope?

A
  • Normal: pale centre and haemoglobin surrounding
  • Target cell: haem centre, pale halo, haem edge

Intro to Med (46 decks)

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