Red and white blood cells Flashcards
What is haemopoiesis?
Formation of red blood cells from the bone barrow from HSC’s
Where are red blood cells produced and what are they derived from?
Bone Marrow
Haemopoietic Stem Cell → Myeloid Progenitor
Foetal haemopoiesis - embyronic yolk sac then fetal liver - all bone marrow in children
How many blood cells does the human body produce per day?
173 million
What two. features do HSCs have?
Self - renew
differentiate into mature cells
What is the life span of an erthyrocyte, platelet, monocyte, neutrophil, eosinophil and lymphocyte?
erthyrocyte 120 days platelet 10 days monocyte several days neutrophil 7-10 hours eosinophil less than neutrophil lymphocyte variable
What does erythropoiesis require?
Iron
Folate and Vit B12
Erythropoietin - made in kidney raised in hypoxia and anaemia
Where is erythropoietin made and when is it released?
Made in the kidney in response to hypoxia and anaemia
What is the difference between haem and non haem iron?
Haem - ferrous Fe(II)- best absorbed
Non-haem - ferric Fe(111) needs to be reduced before being absorbed (hard to bind oxygen)
What is the role of iron in erythropoiesis?
Role in haemoglobin, makes cytochromes a,b,c and p450
What substance reduces iron absorption?
Phytates - often found in non-haem iron sources
What is hepcidin? What is it suppressed by?
Substance that blocks the absorption and release of storage iron by blocking of ferroportin
Suppressed by erythropoietic activity
What affect does erythropoiesis have on iron absorption?
Increases iron absorption by increasing ferroportin in duodenum enterocytes
How do we lose iron?
High levels of iron cause an increase in hepcidin which inhibits ferroportin, which causes iron to stay in the enterocytes rather than go in the blood and is lost when the enterocytes are shed
What is anaemia of inflammation?
Inflammation causes release of hepcidin which blocks ferroportin and keeps iron in the enterocytes which are eventually shed
Why is vitamin B12 and folic acid vital ?
They make dTTP (deoxythymidine triphosphate) which is involved in thymidine synthesis which leads to DNA synthesis
Where is b12 found?
Meat, liver, kidney, fish, oysters, clams, eggs, milk, cheese, fortified cereals
Where is Folic acid found?
Green leady veg, cauliflower, brussels sprouts, liver, kidney, wholegrain cereal, yeast, fruit
How is absorption of B12 done?
Combined with intrinsic factor made in gastric parietal cells > B12-IF can bind to receptors in the ileum
Once in the circulation, B12 is bound to the transport protein transcobalamin.
What can cause vitamin B12 deficiency?
Inadequate intake
pernicious anaemia - Autoantibodies that interfere with the production or function of IF so there is a inadequate secretion of IF so B12 can’t be absorbed:
Malabsorption ie coeliac disease
Lack of acid in stomach
Why are red blood cells only useful for 120 days and how are they removed?
They travel bent and thus stretch in vessels thus get damaged easily
they bind to haptoglobin and are removed by the phagocytic cells of the spleen
What is released when red blood cells are broken down?
Haem which is broken down into billirubin and is released by the liver as bile - iron is returned to bone marrow
Also Amino acids form
What is hypochromia? what is it often associated with?
Hypochromia means that the cells have a larger area of central pallor than normal
This results from a lower Hb content and concentration, and a flatter cell
Hypochromia and microcytosis often go together
What is polychromasia? What can it lead to?
Too red/dark red blood cells
an increased blue tinge to the cytoplasm of RBCs
It indicates the red cell is young
Polychromatic cells are larger than normal red cells i.e. polychromasia is one of the causes of macrocytosis
What does increase in reticulocytes show?
red cells destruction or bleeding
What is microcytic anaemia?
Iron deficiency often results in hypochromia
What is macrocytic anaemia?
B12 and folate deficiency
often results in polychromasia
What is a target cell and what can cause this ?
Accumulation of Hb in centre of the cells where it is usually pale Obstructive jaundice Liver disease Haemoglobinopathies Hyposplensjm
What is anisocytosis?
Variation in size of red blood cell
What is poikilocytosis?
Variation in shape of of red blood cells
What do macrophages store and release?
Iron
How long do monocytes spend in circulation? What do they do?
Monocytes spend several days in circulation
-present antigens to lymphoid cells
-Monocytes migrate to tissues where they develop into macrophages (also known as histiocytes) and other specialised cells that have a phagocytic and scavenging function
can store and release iron
Where do monocytes migrate to and what do they develop into?
Monocytes migrate to tissues where they develop into macrophages (also known as histiocytes) and other specialised cells that have a phagocytic and scavenging function
What causes sickle cell anaemia?
polymerisation of HbS, which in the deoxygenated form is much less soluble than HbA
HbS occurs when one or two copies of an abnormal beta globin gene are inherited
A mutation in the beta haemoglobin gene is the charged glutamic acid residue in position 6 is replaced by an uncharged valine molecule.
Can cause splenic sequestration
Sickle cell SIX GiVes me a crisis
What causes the change in shape of RBCs in sickle cell anaemia?
When they are in a hypoxic environment
What is normal RBC count determined by?
Age Gender Ethnic origin Physiological status Altitude Nutrition Smoking/alcohol
What is the function of neutrophils?
Chemotaxis, phagocytosis, killing phagocytosed bacteria
What is the function of monocytes and macrophages?
Chemotaxis, phagocytosis, killing some micri-organisms and antigen presentation
What is the function of eosinophils granulocytes?
What are some identifying features?
Normal neutrophil function and defence against parasitic infection
regulation of some immediate-type hypersensitivity reactions
2 lobe nucleus
Less time in circulation and more time in tissues
What is the function of basophil granulocytes?
What are some identifying features?
Mediation of some immediate-type hypersensitivity
Modulation of inflammatory responses by releasing histamine, /heparin and proteases
usually 2 lobes but large size and purple colour
What is function of lymphocytes?
Humoral and cellular immunity
Recirculate into lymph nodes and other tissues then go back into the blood stream
variable life span
What do basophils granulocytes contain?
Heparin, histamine and and proteolytic enzymes
What is the structure of neutrophils? How long do they spend in circulation before entering the tissue?
3-5 lobe multi-segmented nucleus
7-10 hours in circulation before migrating to tissues
What is leucocytosis?
Too many white blood cells Neutrophilia Eosinophilia Basophilia Monocytosis Lymphocytosis
What is leucopenia?
Too little white blood cells
Neutropenia
lymphopenia
What can cause neutrophillia?
Neoplasm Infection Corticosteroids Exercise - can cause rapid shift of neutrophils from marginated pool to circulating pool Pregnancy Tissue damage - inflammation/infarction
NICE PreT
What can neutrophilia be accompanied by?
Toxic changes - heavy course granulation of neutrophils
Left shift - more non segmented neutrophils or more neutrophils precursors
What is interleukin?
What do they do?
Interleukin(IL), any of a group of naturally occurring proteins that mediate communication between cells.
Interleukinsregulate cell growth, differentiation, and motility.
They are particularly important in stimulating immune responses, such as inflammation.
What does transferrin do?
Iron in the plasma is bound to the transport protein transferrin, which delivers iron to the bone marrow for erythropoiesis.
When do Folic acid requirements increase?
during pregnancy or during increased red blood cell production ie during sickle cell
What is splenomegaly?
When the spleen is enlarged.
This may happen in sickle cell anaemia due to the shape of blood cells.
Erythrocytes have asickled shapedue to the chain defect in haemoglobin.
This causes them to become trapped in the spleen, making it become enlarged.
What is splenic sequestration? Why doesn’t this occur after 5 years in SCD?
Where blood pools in the spleen since they are defective.
This often tends to co-present withthrombocytopenia.
This can cause the body to go into ahypovolaemic shocksince circulating red blood cells are diminished due to anacutesplenic sequestration crisis.
SCD patients become functionally hyposplenic by around age 5 (due to repeated splenic infarction).
As splenic sequestration can only occur where there is a functional spleen, this complication is not usually seen in older children or adults with SCD.
What growth factors are needed for myeloid cells to proliferate and survive?
GM-CSF - granulocyte macrophage stimulating colony stimulation factor
G-CSF -granolocyte stimulating colony stimulation factor
M-CSF - macrophage stimulating colony stimulation factor
What is spherocytosis and what causes it?
disruption in vertical linkages in membrane
cells are more spherical, lack central pallor
due to loss of membrane but no loss of cytoplasm cells become less flexible and are removed early by the spleen
hereditary
What is eliptocytosis?
Disruption of horizontal linkages in membrane
elongated oval-shaped red blood cells
hereditary
What is the role of Glucose-6-phosphate dehydrogenase?
Vital enzyme in the hexose monophosphate shunt (HMP shunt)
tightly couples to glutathione metabolism which protects the RBCs from oxidant damage
What does a deficiency in Glucose-6-phosphate dehydrogenase lead to?
cells to be vulnerable to oxidant damage - severe intravascular haemolysis as a result of infection or exposure to an exogenous agent
X-linked inheritance
What can you see in a red blood film of someone with G6PD deficiency?
Episodes of intravascular haemolysis associated with the appearance of considerable numbers of irregularly contracted cells/bite cells
small, irregular outline and lost central pallor
Hb denatures and forms round inclusions- heinz bodies
6 steps of chemotaxis?
Adhesion and margination Rolling Tight adhesion Diapedesis Migration Phagocytosis
Where do lymphocytes circulate?
What are the three types?
Lymphocytes recirculate into lymph nodes and other tissues, and then back to the bloodstream
Intravascular life span is very variable
B lymphocytes mature into plasma cells which produce antibodies
T lymphocytes are involved in cell-mediated immunity
NK cells are part of the innate immune system - they can kill tumour cells and virus-infected cells
What are reactive or secondary changes to WBCs?
When normal/healthy bone marrow response to external stimulus ie infection, inflammation or infarction
What are primary blood cell disorders?
leukocyte count or morphology is abnormal due to acquired somatic DNA damage affecting a haematopoietic precursor cell giving rise to blood cancers ie leukaemia, lymphoma etc
What can cause neutropenia?
Benign ethnic neutropenia radiotherapy autoimmune disorders Infections Drugs (anticonvulsants, antipsychotics, antimalarials and chemo)
BRAID
What can cause lymphocytosis?
How is this seen on a blood film?
Often a response to viral infection (transient)
Can result from chronic lymphocytic leukaemia (persistent)
Atypical lymphocytes ie in epstein barr
Scalloped margins - hugging of RBCs
What is chronic myeloid leukaemia caused by?
How can it be treated?
Increase in all granulocytes and their precursors in both the blood and bone marrow
Occurs from a translocation between chromosome 9 and 22 occuring in a single HPS
Philadelphia (ph) chromosome -abnormally short chromosome creates a fusion protein which enables Tyrosine kinase activity - this drives autonomous blood cell proliferation
There is an enlarged spleen
It can be inhibited by tyrosine kinase inhibitors leading to remission and possible cure
What is neutrophil hyper segmentation and what is it caused by?
Increase in the number of neutrophil lobes or segments (right shift)
Results from a lack of vitamin B12 or folic acid - megaloblastic anaemia
What are causes of monocytosis?
Infection - chronic bacterial
chronic inflammation
some types of leukaemia
What can cause eosinophilia?
Allergy or parasitic infections
Asthma, eczema, drugs
can occur in leukaemia - CML
What can cause basophilia?
uncommon - usually due to leukaemia or associated issues
What causes atypical lymphocytes in lymphocytosis ?
May find atypical lymphocytes when its a viral infection
e.g. in Epstein Barr virus infection (infectious mononucleousis)
atypicalities can include
-Basophillic cytoplasm
- Scalloped margins, ‘hugging’ of surrounding RBCs
What is a cause of lymphocytosis in children?
Important cause of lymphocytosis in children is whooping cough (bordatella pertussis)
What is acute lymphoblastic leukaemia ?
increase in immature cells (lymphoblasts) with these failing to develop into mature white blood cells
bone marrow is infiltrated by immature lymphoblasts, resulting in impaired haemopoiesis
lymphoblasts circulate in peripheral blood
Sudden and severe in onset - if not treated patients die quickly
What is Chronic lymphoid leukaemia?
CLL is a lymphoproliferative disorder
CLL is the most common cause of persistent lymphocytosis in
the elderly.
Characterising the profile of cell surface markers expressed by lymphocytes helps determine the cause of the lymphocytosis
Mature, though abnormal cells, excess of b cells
No profound implications so the excess can be tolerate
What are some haematological features of ALL?
Leukocytosis Anaemia - normocytic or normochromic Neutropenia Thrombocytopenia replacement of normal bone marrow cells with lymphoblasts
What is cytogenic and moelcular genetic analysis used for in patients with ALL?
- Useful for managing individual patient as it gives information about prognosis
- Cytogenetic/molecular genetic analysis advances knowledge of leukaemia as it permits the discovery of leukaemogenic mechanism and development of targeted treatmen
What are some treatments for ALL?
• Supportive treatment
○ Red cells
○ Platelets
○ Antibiotics
• Systemic chemotherapy (bone marrow and blood disease targeting)
• Intrathecal chemotherapy ➖ drugs that cross the blood brain barrier to prevent relapse
What can cause lymphopenia?
HIV Chemotherapy Radiotherapy Corticosteroids in normal blood most lymphocytes are CD4+ T cells
What is red blood cell function dependent on?
Integrity of membrane
haemoglobin structure and function
cellular metabolism
What is a schistocyte?
Small pieces of Red blood cells - fragmentation
Can occur from a shearing process by the platelet rich red blood clots in small blood vessels
What is a schistocyte?
Small pieces of Red blood cells - fragmentation
Can occur from a shearing process by the platelet rich red blood clots in small blood vessels
How can you detect reticulocytes?
Stain red blood cells with new methylene blue and higher RNA can be seen
Response to bleeding or destruction
What type of distribution does haemoglobin concentration in red blood cells show?
Gaussian normal distribution
What is a cause of lymphocytosis in children?
Whooping cough in children leads to increased white blood cells
Bordatella pertussis
