Haematopoiesis

Haematopoiesis

Formation of new blood cells

Where does haematopoiesis occur in the foetus and after birth

Foetus: Liver, spleen, blood
After birth: Mainly bone marrow

Describe pathways for each type of blood cell from hematopoietic stem cell to mature cell.

Where are haematopoietic stem cells & how do they work?

Self-renewing multipotent stem cells.
Reside in bone marrow.
Respond to haematopoietic growth factors

How is acute lymphoblastic leukaemia (ALL) diagnosed

Based on very high numbers (20%) of abnormal lymphoblasts.
Often have reduced neutrophil counts & decreased counts of other cells from the myeloid lineage, due to overcrowding.

How is chronic myeloid leukaemia diagnosed

Extremely high WBC count & high platelet count
Often asymptomatic diagnosis around age 56

Erythrocytes lifespan & requirements

120 day lifespan
Require iron, vitamin B12 & folic acid

How is erythrocyte production stimulated

(Stimulated by hypoxia) Erythropoietin (EPO) is secreted by the kidneys & binds to receptors on pronormoblasts (precursor to RBC) in bone marrow.
Half life of 7-8 hrs

At what stage does an erythrocyte lose its organelles

How long does this process take

As the early normoblast differentiates further, haemoglobin synthesis & iron accumulation occur. When haemoglobin has accumulated, the cell ejects its organelles.
Cell becomes biconcave shape.
Process takes 15 days

Where is iron in body from?

Absorbed from diet in small intestine
Recycled from dead RBCs

How to spot anaemia

Low ferritin level is the most sensitive index of early iron deficiency

Low RBC count

Low haemoglobin

Low haematocrit

Erythrocytes may be microcytic …→

Low Mean Corpuscular Volume (MCV)

Erythrocytes may be hypochromic

Low Mean Corpuscular Haemoglobin (MCH)

Target cells and pencil cells

Folic acid & vitamin B12 functions

DNA synthesis
Deficiency causes normoblast apoptosis (cell death)

How is vitamin B12 taken in

Binds to intrinsic factor in stomach and is absorbed in the ileum

How might someone become B12 deficient

Age-related absorption problems
Strict vegan diet
Pernicious anaemia (intrinsic factor not produced)

Anaemia

Anaemia is a condition in which either the number of erythrocytes or the haemoglobin within them is lower than normal

Types of anaemia

Haemorrhagic anaemias (due to either sudden or persistent blood loss)
Haemolytic anaemias (Erythrocytes rupture prematurely -> haemoglobin abnormalities, transfusion mismatch, infections)
Aplastic anaemia (destruction/inhibition of bone marrow -> chemicals, ionising radiation, viruses)
Sickle Cell anaemia

Haemochromatosis
(i) what is it
(ii) symptoms
(iii) cause
(iv) treatment

(i) Iron overload
(ii) Abdominal pain, weakness, fatigue, joint pain, liver disease, endocrine & cardiac abnormalities
(iii) Mutation of HFE gene
(iv) Regular phlebotomies

Polycythemia Vera
(i) what is it
(ii) cause
(iii) risks

(i) Myeloproliferative disorder of RBCs (overproduction)
(ii) Genetic mutation leads to Oversensitivity to EPO
(iii) Increased risk of thrombotic events (stroke/DVT)

Haematology Tests

Complete Blood Cell Count (CBC)
RBC count
Total/differential WBC Count
Platelet count
Haematocrit (Packed Cell Volume)
Haemoglobin (Hb %)
Iron profile

What's the rouleaux effect?

Stacking of RBCs

Mean corpuscular volume (MCV)(average volume of a RBC) formula & normal value

MCV = haematocrit/RBC (cells/L)
Normal value = 80-100fL

Normocytic vs Microcytic vs macrocytic

What are microcytic & macrocytic lacking

Normocytic = within MCV range of 80-100fL
Microcytic = < 80fL (usually iron deficient)
Macrocytic = > 100fL (lack of vitamin B12 or folic acid)

Mean Corpuscular Haemoglobin (MCH)(average quantity of haemoglobin per cell) formula & normal value

MCH = haemoglobin (g/L)/RBC (cells/L)
Normal values = 27-31 (pg/cell)

Mean Corpuscular Haemoglobin Concentration (MCHC)(average haemoglobin quantity in a volume of cells) formula & normal values

MCHC = MCH/MCV
Normal values = 32-36 g/dL or 32-36% Hb per cell