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Lily PoM Haematology > Red Blood Cells > Flashcards

Red Blood Cells Flashcards

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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
What are the two forms of dietary iron?
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 ```
26
Why is it important that iron levels are regulated?
There is no physiological mechanism for regulating iron excretion Iron can form free radicals that damage bodily tissues
27
How is iron transported around the body?
In the plasma | Bound to the protein transferrin
28
Where is iron stored?
In the liver | As the protein ferritin
29
What is the role of hepcidin?
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
Is hepcidin synthesis stimulated or surpresses by erythropoiesis?
Surpressed
31
When storage iron is high what happens to the synthesis of hepcidin?
It is increased It then binds and degrades ferroportin Therefore when the enterocyte dies the iron is lost
32
In inflammation cytokines such as interferon and interleukins are released. What is the effect of these on erythropoiesis?
Reduction The interleukin and Thmor necrosis factor increase hepcidin levels
33
What are folate and vitamin B12 used for?
The synthesis of thymidine (dTTP) | Needed for DNA synthesis
34
Which rapidly deciding cells are especially effected by vitamin B12 and folate deficiency?
Bone marrow Epithelial surfaces of mouth and gut Gonads
35
Where do we get vitamin B12?
Only animal derived foods: ``` Meat Fish Oysters Eggs Milk Cheese Fortified cereals ```
36
Where do we get folate?
``` Green leafy veg Cauliflowers Sprouts Liver and kidney Cereals Yeast Fruit ```
37
What happens to vitamin B12 once ingested?
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
How can vitamin B12 deficiency arise?
Veganism Lack of HCL (acorhydria) Inadequate secretion if IF -pernicious anemia Malabsorption E.g. coeliac
39
Where is folate absorbed?
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
What happens to RBCs at the end of their life cycle?
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
What does the function of RVCs depend on?
Integrity of membrane Harmoglobin structure Cellular metabolism A defect in any of these results in a shortened lifecycle (haemolysis)
42
What is the shave of a red blood cell?
Biconcave disc Helps with manoeuvrability through small blood vessels
43
What is the membrane of a red blood cell made of and what is it’s function?
Lipid bilayer supported by a protein cyto skeleton and contains transmembrane proteins Maintain integrity and the elasticity/deformability of the red blood cell
44
What are some examples of transmembrane and skeletal proteins In RBCs?
Transmembrane: Rhesus and band 3 Skeletal: Spectrin
45
What happens when there is a disruption of vertical linkages in the membrane (spectrin)?
Hereditary sphericytosis
46
What are some properties of spherocytes?
``` Smaller Round No central pallor Regular outline Smaller membrane but same cytoplasm ``` Less flexible so are removed prematurely by the spleen (haemolysis)
47
What happens when the horizontal linkages across the membrane are disrupted?
Hereditary elliptocytosis | Also happens in iron deficiency
48
What is the main function of erythrocytes?
To transport oxygen from the lungs to the tissues Able to do this because of the haem moiety
49
How many harmoglobin molecules in one RBC?
~300 million
50
What is the make up if haemoglobin A (adults) ?
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
How is foetal haemoglobin F differ from haemoglobin 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
What is the shape of the oxygen Hb dissociation curve?
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
What does the position of the haemoglobin depend on?
pH CO2 in RBCs Structure Conc of 2,3-DPG
54
What is the Bohr effect? How do the shifts work?
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
What is the metabolism in a RBC adapted for?
The generation of ATP Maintainence of Hb function, integrity of the membrane and the RBC volume
56
What is 2,3-DPG
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
What is G6PD?
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
What is G6PD deficiency?
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
What are irregularly contracted cells?
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
How is the size of RBCs described?
Microcytic Smaller Normocytic Normal Macrocytic Bigger
61
What are some causes of microcytosis
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
What are some types of macrocytes?
Round Oval Polychromatic (young immature red blood cells )
63
What are some causes of macrocytosis?
Lack of vitamin B12 or folate Liver disease and ethanol toxicity Areas with high amounts Haemolysis of polychromatic cells Pregnancy
64
What is hypochromia?
Larger area of central pallor Less haemoglobin Often goes with microcytisis Causes include iron deficiency and thalassemia
65
What is polychromasia?
A blue tinge to the cytoplasm of a red cell Indicates the cell is young and immature Goes with macrocytosis
66
What is a new methylene blue stain used for?
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
What is a variation in size of red blood cells called?
Anisocytosis Eg in patients who have had a transplant
68
What is poikilocytosis?
Higher variation in shape than usual
69
What are target cells?
Accumulation of Hb in the area of central pallor ``` Cause by: Obstructive jaundice Liver disease Haemaglobinopathies Hyposplenism ```
70
What are sickle cells?
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
What are red cell fragments?
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

Lily PoM Haematology (6 decks)

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