Red Blood Cells Flashcards
What do all blood cells originate from?
Haematopoetic stem cells
Where does foetal haematopoeisis start?
The yolk sac
Which bones in children does haematopoiesis occur in?
All bones
Which bones in adults does haematopoiesis occur in?
Long bones - femur, pelvis, sternum
What are the two characteristics of HSC?
The can self renew and they can differentiate
What are the two cells that HSC differentiate into?
Common Lymphoid Progenitor and Common Myeloid Progenitor
What is the intravascular life span of red blood cells?
120 days
Where does erythropoiesis occur?
Bone Marrow
What is HAEM iron also known as?
Ferrous iron - fe2+
What is non-HAEM iron also known as?
Ferric iron - fe3+
What affect do phytates have on iron absorption?
They reduce it
What organs is excess iron toxic to?
Heart and liver
Where is ferroportin found?
In duodenum enterocytes
How do we lose iron if it is high?
Higher iron leads to HEPCIDIN release, which blocks ferroportin, so iron cannot leave the enterocytes. Therefore when the enterocyte is destroyed so is the iron stored within it
What does inflammation do to Hepcidin?
Increases hepcidin, and therefore can lead to anaemia of inflammation as there is not enough iron in the blood as it is all being kept within the enterocytes
Why do we need Folate and Vitamin B12?
They are needed for dTTP synthesis - thymidine, needed for DNA synthesis
What can a Vitamin B12 and Folate deficiency cause?
Megaloblastic erythropoiesis - this is because the cells keep dividing but lack the DNA
Name three sources of Folate
Green leafy vegetables, cauliflower and Brussels sprouts
Name three sources of B12
Meat, fish, clams
What does B12 combine with so it can be absorbed?
Intrinsic factor which is made in the gastric parietal cells
What causes vitamin B12 deficiency
Inadequate intake, pernicious anaemia and malabsorption
What is pernicious anaemia?
This is where your body does not make IF therefore the B12 cannot bind and therefore cannot be absorbed
Why do red blood cells have a life span of 120 days?
When they move through capillaries and blood vessels, the walls bend and stretch meaning they get damaged
Where are the red blood cells destroyed?
Spleen
What are the RBCs broken down into?
HAEM and globin
What does the HAEM part of the RBC after it is destroyed?
Gets broken down into bilirubin
How is bilirubin excreted
In bile
Why is bile important
Contains bile salts which are needed for the emulsification of fats so they can be absorbed
What are the three types of granulocytes
Neutrophil, basophils and eosinophil
What does hypochromia mean?
Too little haemoglobin so pale
What is a polychromatic RBC?
One that is too read due to too much haemoglobin
What are target cells?
When you have an accumulation of hemoglobin in the area of central pallor
What causes the presence of target cells?
Jaundice, liver disease, hyposplenism
What does anisocytosis mean
Variation in size
What does poikilocytosis mean
Variation in shape
What causes sickle cells?
Due to the polymerisation of HbS which forms tachtoids that distort the shape of the RBC
What is the mutation that causes sickle cell disease? SICKLE CELL SIX GIVES ME A CRISIS
Charged glutamic acid residue at positive 6 in beta Hb gene is replaced by uncharged valine
“Normal” Hb is determined by many things like..
Gender and physiological status eg altitude
What type of distribution fo Hb concentrations show?
Gaussian distribution
An infant with sickle cell anaemia (HbSS) develops symptoms of fatigue and pain. Blood tests reveal anaemia with thrombocytopenia. Examination reveals a mass on the left-hand side of his abdomen. Given this information, what could be the most likely explanation for his symptoms?
Pooling of blood in the spleen - spleenic sequestration
What is Crohn’s Disease?
inflammatory bowel disease which often involves ulcer formation in the mucosal layer of the intestines.
How can Crohn’s disease lead to iron-deficiency anaemia?
Crohn’s disease can lead ulcer formation in the stomach, meaning internal bleeding can occur. This may result in iron-deficiency anaemia due to blood loss
What regulates the proliferation and differentiation of Haematopoietic stem cells?
Haematopoietic growth factors
A 28-year old female has some tests carried out following a full blood count that subsequently reveal that she is folate deficient. What changes in the red blood cells would you expect to see.
Macrocytic cells
Which cells do myeloid stem cells give rise to?
Red blood cells, granulocytes, monocytes, mast cells and basophils
What is the life span and function of a platelet?
10 Days - Haemostasis
What is the life span and function of a monocyte?
Several days, defense against infection by phagocytosis
What is the life span and function of a neutrophil?
7-10 hours - defense against infection by phagocytosis and killing of micro-organisms
At what point does the liver take over haematopoiesis in the foetus?
6-8 weeks gestation
What are haematopoietic growth factors?
Glycoprotein hormones which bind to cell surface receptors
Regulate proliferation and differentiation of HSCs
Regulate function of mature blood cells
What is the haematopoietic growth factor which influences red cell production?
Erythropoietin
What are the haematopoietic growth factors which influence granulocyte and monocyte production?
G-CSF, G-M CSF, cytokines e.g. interleukins
Which common progenitor do megakaryocytes derive from?
Myeloid
What are three causes of microcytic anaemia?
Iron deficiency
Pregnancy
Childhood
What are three causes of macrocytic anaemia?
(B12/folate deficiency)- alcohol excess, pregnancy, vegan diet
What are the two main functions of iron?
Oxygen transport in haemoglobin
Mitochondrial proteins
cytochromes a, b and c: for production of ATP
Why is ferric iron not as easily absorbed?
and requires action of reducing substances (e.g. vitamin C) for absorption
How does anaemia of chronic disease/inflammation occur?
Pro-inflammatory cytokines such as IL-1, TNF-alpha, IL-6 and IFN-gamma work to decrease EPO production, and increase hepcidin - increased hepcidin means less iron absoprtion in the gut as hepcidin binds to ferroportin, meaning iron is unable to leave theenterocytes and therefore is destroyed when the entoercytes die
When is hepcidin released?
Released from the liver in response to high storage iron
What can cause a deficiency in B12?
inadequate intake e.g. veganism
- inadequate secretion of IF: pernicious anaemia (an autoimmune disorder)
Malabsorption e.g. coeliac disease
lack of acid in stomach (achlorhydria)
During what situations do the requirements for folic acid increase?
During pregnancy and during red cell production
What three things does erythrocyte function depend on?
Integrity of the membrane
Haemoglobin structure and function
Cellular metabolism
What structures help t maintain the integrity and shape of the red cell?
The red cell membrane - made of lipid bilayers which is supported by proteins and contains transmembrane proteins
What are the transmembrane proteins found in red cell membrane?
Band 3 and rhesus
What are the skeletal proteins found in red blood cells membrane?
Spectrin and junctional
What does a disruption to vertical linkages in the red blood cell membrane cause?
Hereditary Spherocytosis
What would be seen on a blood film of a patient with hereditary spherocytosis?
Rounded, with a regular outline and lacking central pallor
Disruption of horizontal
linkages in red cell membrane produces…
Hereditary elliptocytosis
How does deficiency in G6PD affect red cells?
- G6PD is an important enzyme in the HMP shunt
- The HMP shunt is involved in metabolism of glutathione which protects the red cell from oxidant damage
- Therefore deficiency of G6PD causes red cells to be vulnerable to oxidant damage
What protects the red cells from oxidant damage?
Glutathione
What does G6PD deficiency cause?
G6PD deficiency usually causes intermittent, severe intravascular haemolysis as a result of infection or exposure to an exogenous oxidant
What are episodes of intravascular haemolysis associated with the appearance of?
considerable numbers of Irregularly contracted cells/ ‘bite cells’
