Red Blood Cells Flashcards

1
Q

What is the making of red plaid cells called?

A

Haemopoiesis

Blood-making

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2
Q

Where where are red blood cells produced?

A

The bone marrow

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3
Q

What pluripotent cells to RBCs develop from?

A

Haemopoietic stem cells
HSCs

These are distributed in an ordered fashion in the bone marrow amongs mesenchymal, endothelial cells and the vasculature which they interact with.

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4
Q

HSCs give rise to two types of stem cells?

A

Lymphoid stem cells

Myeloid stem cells
From which red cells, granulocytes, monocytes and platelets are developed

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5
Q

What is the approximate lifespan of a RBC?

A

120 days

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6
Q

How many blood cells are produced each day on average?

A

500 billion

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7
Q

How are HSCs able to regulate the numbers of each type of blood cell? (Two characteristics)

A

Self renewing:
Some daughter cells remain as HSCs so the pool of HSCs is not depleated

Differentiate into mature progeny:
The other daughter cells are committed to follow the differentiation pathway

This Balances the numbers of each blood cell being made and destroyed

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8
Q

What blood cells come from the common myeloid progenitor?

A

Slide photo

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9
Q

Where are HSCs derived from in the embryo?

A

After the first 3 weeks of gestation, the mesoderm in the yolk sac.

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10
Q

After the 3 weeks where does haemopoiesis take place?

A

The liver

Main source until shortly before birth

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11
Q

When does the bone marrow start developing haemopoietic activity?

A

Around 10 weeks In to gestation

After birth it becomes the only site of haemopoiesis

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12
Q

What is the difference In the sites of haemopoiesis between children and adults?

A

Children
Bone marrow of all bones

Adults
Bone marrow of pelvis, sternum, vertebrae, the proximal ends of the femur and humorous
(Although all bones maintain the ability, they just don’t always use it)

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13
Q

How is haemopoiesis regulated?

A

Genes, transcription factors, growth factors, the microenvironment

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14
Q

What are haemopoietic growth factors?

A

Glycoprotein hormones which bind to cell surface receptors

Regulate proliferation and differentiation of HSCs

Regulate function of mature blood cells

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15
Q

Which growth factor leads to the proliferation of RBCs?

A

Erythropoietin

Produced in the kidney, stimulated by reduced oxygen supply

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16
Q

What growth factors lead to the proliferation of granulocytes and monocytes?

A

Cytokines e.g. interleukins

G-CSF
Granulocyte colony stimulating factors

G-M CSF
Granulocyte macrophage

All produced in the bone marrow

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17
Q

Which growth factor controls megakaryopoiesis and platelet production?

A

Thrombopoietin

Produced in the bone marrow

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18
Q

Give an overview of where each blood cell differentiates from?

A

Last slide of RBC part 1

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19
Q

What are the stages of development to an RBC?

A

Common myeloid progenitor
Erythroblasts
Erythrocytes

The process involves cell division until it reaches the late erythroblast stage when it extrudes it’s nucleus. At this stage it is polychromatic

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20
Q

What is required for erythropoiesis?

A

Iron
Vitamin B12
Folate
Erythropoietin

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21
Q

How do the different types of anemia affect RBC size?

A

Iron: microcytic

B12/folate: macrocytic

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22
Q

What are the main functions of iron?

A

Oxygen transport in harmoglobin

Mitochondrial proteins:
Cytochromes a b and c for ATP production 
Apoptosis 
Respiration 
Cell cycle arrest 
DNA synthesis
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23
Q

Where is iron absorbed?

A

Duodenum in the small intestine

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24
Q

How much iron is consumed a day, and how much is absorbed?

A

10-20 mg consumed

1-2mg absorbed

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25
Q

What are the two forms of dietary iron?

A

Haem
Ferrous FE2+
Best absorbed
Animal derived

Non haem
Ferric FE3+
Required vitamin C to be absorbed
E.g. soya beans, spinach 
Often contain ohytates which bind to iron making it harder to absorb
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26
Q

Why is it important that iron levels are regulated?

A

There is no physiological mechanism for regulating iron excretion

Iron can form free radicals that damage bodily tissues

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27
Q

How is iron transported around the body?

A

In the plasma

Bound to the protein transferrin

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28
Q

Where is iron stored?

A

In the liver

As the protein ferritin

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29
Q

What is the role of hepcidin?

A

When iron stores of ferritin are full more hepcidin is released. This prevents absorption.

A need for more erythropoiesis leads to a reduction in hepcidin, and more iron absorption

30
Q

Is hepcidin synthesis stimulated or surpresses by erythropoiesis?

A

Surpressed

31
Q

When storage iron is high what happens to the synthesis of hepcidin?

A

It is increased
It then binds and degrades ferroportin
Therefore when the enterocyte dies the iron is lost

32
Q

In inflammation cytokines such as interferon and interleukins are released. What is the effect of these on erythropoiesis?

A

Reduction

The interleukin and Thmor necrosis factor increase hepcidin levels

33
Q

What are folate and vitamin B12 used for?

A

The synthesis of thymidine (dTTP)

Needed for DNA synthesis

34
Q

Which rapidly deciding cells are especially effected by vitamin B12 and folate deficiency?

A

Bone marrow
Epithelial surfaces of mouth and gut
Gonads

35
Q

Where do we get vitamin B12?

A

Only animal derived foods:

Meat
Fish 
Oysters
Eggs
Milk
Cheese
Fortified cereals
36
Q

Where do we get folate?

A
Green leafy veg
Cauliflowers 
Sprouts
Liver and kidney 
Cereals
Yeast 
Fruit
37
Q

What happens to vitamin B12 once ingested?

A

Stomach:
Cleaved from food proteins by HCL
Binds to intrinsic factor

Small intestine (duodenum):
B12-IF binds to receptors in the ileum and is absorbed

Once absorbed binds to the transport protein transcobalamin

38
Q

How can vitamin B12 deficiency arise?

A

Veganism

Lack of HCL (acorhydria)

Inadequate secretion if IF
-pernicious anemia

Malabsorption
E.g. coeliac

39
Q

Where is folate absorbed?

A

Small intestine
Duodenum and jejunum

Total body stores are around 10mg and last 3 months

Demand increases during pregnancy
And diseases which involve increased red cell production

40
Q

What happens to RBCs at the end of their life cycle?

A

Phagocytosis by reticuloendothelial macrophages one the spleen

The the iron in the haem ring is recycled, bound to transferrin and taken to the bone marrow to produce more RBC

The haem is broken down to bilirubin which is excreted one bile

41
Q

What does the function of RVCs depend on?

A

Integrity of membrane
Harmoglobin structure
Cellular metabolism

A defect in any of these results in a shortened lifecycle (haemolysis)

42
Q

What is the shave of a red blood cell?

A

Biconcave disc

Helps with manoeuvrability through small blood vessels

43
Q

What is the membrane of a red blood cell made of and what is it’s function?

A

Lipid bilayer supported by a protein cyto skeleton and contains transmembrane proteins

Maintain integrity and the elasticity/deformability of the red blood cell

44
Q

What are some examples of transmembrane and skeletal proteins In RBCs?

A

Transmembrane:
Rhesus and band 3

Skeletal:
Spectrin

45
Q

What happens when there is a disruption of vertical linkages in the membrane (spectrin)?

A

Hereditary sphericytosis

46
Q

What are some properties of spherocytes?

A
Smaller
Round
No central pallor 
Regular outline 
Smaller membrane but same cytoplasm 

Less flexible so are removed prematurely by the spleen (haemolysis)

47
Q

What happens when the horizontal linkages across the membrane are disrupted?

A

Hereditary elliptocytosis

Also happens in iron deficiency

48
Q

What is the main function of erythrocytes?

A

To transport oxygen from the lungs to the tissues

Able to do this because of the haem moiety

49
Q

How many harmoglobin molecules in one RBC?

A

~300 million

50
Q

What is the make up if haemoglobin A (adults) ?

A

4 subunits
Each comprised of a globin chain

2 alpha globin chains
2 beta globin chains
All bound to a haem group

The haem group is comprised of a ferrous iron (2+), held in a porphyrin ring

Each Fe2+ binds to 1 oxygen

So 4 oxygen molecules per RBC

51
Q

How is foetal haemoglobin F differ from haemoglobin A?

A

2 alpha globin chains
2 gamma globin chains

As opposed to two alpha and two beta

A small amount of haemoglobin F persists throughout adult life

52
Q

What is the shape of the oxygen Hb dissociation curve?

A

Sigmoid

Partial pressure on x
% saturation on right

Sigmoid is due to cooperativity (first oxygen bound creates a conformational change so the next is easier)

53
Q

What does the position of the haemoglobin depend on?

A

pH
CO2 in RBCs
Structure
Conc of 2,3-DPG

54
Q

What is the Bohr effect? How do the shifts work?

A

Increased CO2 means decreased pH

Shift to the right

Easier unloading of O2

Also with high 2,3-DPG
And sickle haemoglobin

Foetal haemoglobin has a higher oxygen affinity (left shift)

55
Q

What is the metabolism in a RBC adapted for?

A

The generation of ATP

Maintainence of Hb function, integrity of the membrane and the RBC volume

56
Q

What is 2,3-DPG

A

2,3-diphosphoglycerate

Binds to the beta globin chain,modulates the oxygen affinity of haemoglobin

Plays an important role in the adaptive response to anaemia, hypoxia and high altitude

57
Q

What is G6PD?

A

An important enzyme in the hexose monophosphate shunt

Coupled to the metabolism of glutathione, protecting cells from oxidant damage

Oxidants can be generated in the blood, or come from diet (e.g. broad beans)

G6PD deficiency can lead RBCs to become vulnerable to oxidant damage

58
Q

What is G6PD deficiency?

A

Most prevalent enzyme disorder

X linked, so infected individuals are usually hemizygous males

Causes intermittent severe intravascular haemolysis as a result of infection or exposure to an exogenous oxidant (e.g. broad beans or drugs)

59
Q

What are irregularly contracted cells?

A

They have an irregular outline
Smaller
Have lost their central pallor
Also called hemighosts

Usually result from oxidant damage to cell membrane and haemoglobin

Haemoglobin is denatured and forms Heinz bodies, a specific test detects these

60
Q

How is the size of RBCs described?

A

Microcytic
Smaller

Normocytic
Normal

Macrocytic
Bigger

61
Q

What are some causes of microcytosis

A

Defects in haem synthesis
Caused by iron deficiency Or anaemia of chronic disease

Defects in globin synthesis (thalassaemia)
Eithe alpha or beta chain synthesis

62
Q

What are some types of macrocytes?

A

Round
Oval
Polychromatic (young immature red blood cells )

63
Q

What are some causes of macrocytosis?

A

Lack of vitamin B12 or folate

Liver disease and ethanol toxicity

Areas with high amounts Haemolysis of polychromatic cells

Pregnancy

64
Q

What is hypochromia?

A

Larger area of central pallor

Less haemoglobin

Often goes with microcytisis

Causes include iron deficiency and thalassemia

65
Q

What is polychromasia?

A

A blue tinge to the cytoplasm of a red cell

Indicates the cell is young and immature

Goes with macrocytosis

66
Q

What is a new methylene blue stain used for?

A

To look for young cells with reticulocytes that have higher rna content

Reticulocytosis refers to increased numbers of reticulocytes

May occur in areas of bleeding or haemolysis

67
Q

What is a variation in size of red blood cells called?

A

Anisocytosis

Eg in patients who have had a transplant

68
Q

What is poikilocytosis?

A

Higher variation in shape than usual

69
Q

What are target cells?

A

Accumulation of Hb in the area of central pallor

Cause by:
Obstructive jaundice 
Liver disease
Haemaglobinopathies 
Hyposplenism
70
Q

What are sickle cells?

A

Crescent shape

Result from the polymerisation of haemoglobin S, which when deoxygenated is much less soluble than haemoglobin A

Occurs when two abnormal copies of the beta globin gene are inherited

In beta globin an charged glutamic acid is replaced by an uncharged valine molecule

71
Q

What are red cell fragments?

A

Also know as shistocytes
Fragmented red cells
May result from a shearing process caused by platelet rich blood cells such as in disseminated intravascular coagulation