WEEK 1: Haematopoiesis and Anaemias

Question 1

what’s the main function of rbcs?

Answer 1

transport O2 and CO2

Question 2

what’s the main function of neutrophils?

Answer 2

phagocytose and destroy invading bacteria

Question 3

what’s the main function of eosinophils?

Answer 3

destroy larger parasites and modulate allergic inflammatory responses

Question 4

what’s the main function of basophils?

Answer 4

release histamine

Question 5

what’s the main function of monocytes?

Answer 5

become tissue macrophages, which phagocytose and digest invading microorganisms and foreign bodies as well as damaged senescent cells

Question 6

what’s the main function of B cells?

Answer 6

making antibodies

Question 7

what’s the main function of T cells?

Answer 7

kill virus infected cells and regulate activities of other leucocytes

Question 8

what’s the main function of NK cells?

Answer 8

kill virus infected cells and some tumour cells

Question 9

what’s the main function of platelets?

Answer 9

initiate blood clotting

Question 10

what does totipotent mean?

Answer 10

form all cells including extraembryonic and placental cells

Question 11

what does pluripotent mean?

Answer 11

give rise to all cell types

Question 12

what does multipotent mean?

Answer 12

give rise to more than one cell type but limited, eg all blood cells have common ancestral cell - multipotent stem cell

Question 13

what is the stem cell theory of haematopoiesis?

Answer 13

• All cells derived from a pool of stem cells that are self-renewing
• Pluripotential & multipotential stem cells give rise to committed stem cells for each cell line
• Committed stem cells have receptors for specific growth factors
• Respond to stimulation by division & maturation (precursor cell stages) into end-stage cells

Question 14

what are the characteristics of hematopoietic stem cells?

Answer 14

• Stem cells defined as capable of both self
  renewal and multi-lineage differentiation
• HSC are multi-potent stem cells that occur at a
  frequency of 1:5000 in bone marrow
• HSC can be defined by:
  Function: the capacity to give rise to non-self renewing populations that generate multiple terminally-differentiated cell types

Question 15

explain the development of blood cells in a fetus.

Answer 15

3 wk : formation of blood islands from yolk sac​

6 wk : liver becomes hematopoietic organ​

6-8 wk : spleen (until 8th month)​

~20wk : bone marrow (life-long)

Question 16

what is a stem cell niche?

Answer 16

a specific site (microenvironment) in adult tissues where stem cells reside​ and undergo renewal and differentiation​

Question 17

which 2 distinct hematopoietic niches does bone marrow harbour and where?

Answer 17

(1) Osteoblastic niche at the endosteal surface​
(2) Vascular niche involving sinusoidal blood vessels

Question 18

what function does the osteoblastic niche have to help balance self-renewal with differentiation?

Answer 18

Osteoblastic niche maintains quiescence and harbours the Long Term-HSC

Question 19

what function does the vascular niche have to help balance self-renewal with differentiation?

Answer 19

Vascular niche supports proliferation, differentiation and mobilization (transendothelial migration) of Short Term-HSC to the blood stream in response to physiological demands and act as back up outside the BM for HSC during times of BM stress

Question 20

what is erythropoiesis ?

Answer 20

the generation of red blood cells

Question 21

what are the stages of erythropoiesis?

Answer 21

Proerythroblast
Erythroblast
Normoblast
Reticulocyte
Erythrocyte (fully mature red blood cell)

Question 22

how long is the erythropoiesis process?

Answer 22

5-7 days

Question 23

what is a proerythroblast?

Answer 23

it is the first committed to rbc

Question 24

what is a reticulocytye?

Answer 24

a young red blood cell

Question 25

what are 3 characteristics of reticulocytes?

Answer 25

- still have small amounts of RNA​ - tend to stain more blue than mature RBC’s on Wright stain (polychromatophilic)​ - slightly larger than mature RBC​ - undergo removal of RNA on passing through spleen in 1st day of life​ - important marker of RBC production​

Question 26

what is a common myeloid progenitor? (CMP)

Answer 26

a stem cell specialised with the ability to mature into all of the different blood cell types

Question 27

what is an erythrocyte?

Answer 27

a mature red blood cell

Question 28

how long does it take a reticulocyte to become an erythrocyte?

Answer 28

approx. 1 week

Question 29

what is erythropoietin?

Answer 29

a hormone that stimulates the production of rbcs. Erythropoietin levels increase with decrease in hemoglobin.

Question 30

what is the structure of erythropoietin?

Answer 30

165 amino acid glycoprotein with 4 carbohydrate chains

Question 31

what produces erythropoietin and where?

Answer 31

it is produced predominantly by specialised cells called interstitial cells in the kidney

Question 32

why do rbcs have no nucleus and no mitochondria?

Answer 32

enhances flexibility, increases size, increasing O2 ​ carrying capacity

Question 33

how do rbcs make atp?

Answer 33

glycolysis of glucose to pyruvate forming Adenosine TriPhosphate (ATP) and Nicotinamide Adenine Dinucleotide (NADH)​ and lactate.

Question 34

list some extrinsic abnormalities that can cause anaemia

Answer 34

- blood loss - infection - hypersplenism - chemical/physical

Question 35

list some intrinsic abnormalities that can cause anaemia

Answer 35

- membrane defect - enzyme defect - globin abnormalities

Question 36

what measurements of haemoglobin cause anaemia in men and women according to WHO?

Answer 36

< 13g/dL (men), <12g/dL (women), <11g/dL if pregnant

Question 37

what are some symptoms of anaemia? give 4

Answer 37

-Weakness​ - Shortness of breath​ - Pallor​ - Fatigue​ - Palpitations/Tachycardia (pulse >100/min​ - Jaundice​ - Koilonychia (spoon nails)​ - Dark urine​ - Dizziness

Question 38

what is normocytic anaemia?

Answer 38

patient has normal sized rbcs but a reduced number of them

Question 39

what is haemolytic anaemia?

Answer 39

patient's rbcs are destroyed faster than they are synthesized

Question 40

what are some causes of normocytic anaemia?

Answer 40

bleeding, chronic disease, bone marrow failure, many haemolytic anaemias

Question 41

what is macrocytic anaemia?

Answer 41

Macrocytic anaemia is a blood disorder that happens when your bone marrow produces abnormally large red blood cells. These abnormal blood cells lack nutrients red blood cells need to function normally.

Question 42

what is microcytic anaemia?

Answer 42

the presence of small rbcs. Most common cause is iron deficiency

Question 43

what is polycythemia vera?

Answer 43

a type of blood cancer where there is an increase in production of all blood cells

Question 44

what is erythemia?

Answer 44

increase in rbcs

Question 45

what 4 ways is anaemia diagnosed?

Answer 45

- Physical examination​ - Full blood count​ - Reticulocyte count​ - Bone marrow biopsy

Question 46

what 4 factors are observed in a RBC assessment?

Answer 46

- number - size - shape - colour

Question 47

what is aplastic anaemia?

Answer 47

anaemia occurring when bone marrow does not function.

Question 48

what causes aplastic anaemia?

Answer 48

damage to stem cells inside bone marrow due to infections, tumours, autoimmune disease or drugs.

Question 49

how is aplastic anaemia treated?

Answer 49

transfusions, corticosteroids, bone marrow transplant

Question 50

what can cause macrocytic anaemia?

Answer 50

- disorder of DNA synthesis - B12 or folate deficiency

Question 51

what are the 3 main types of anaemia?

Answer 51

normochromic/normocytic microcytic macrocytic

Question 52

why does a shortened life span of rbcs not always lead to anaemia?

Answer 52

bone marrow can increase production 6-8 fold and maintain normal Hb level.

Question 53

what is intravascular haemolysis?

Answer 53

destruction of rbcs within circulation.

Question 54

what is extravascular haemolysis?

Answer 54

premature destruction of rbcs in the spleen/bone marrow

Question 55

why does extravascular haemolysis cause jaundice?

Answer 55

destroyed rbcs are removed by macrophages. Haem breakdown in macrophage generates bilirubin. Bilirubin is released and bound onto albumin to the liver for conjugation and excretion in bile. Rise in unconjugated bilirubin. Jaundice occurs.

Question 56

what is intrinsic haemolytic anaemia?

Answer 56

it is hereditary and a defect in the rbc is causing it

Question 57

what are some examples of intrinsic haemolytic anaemia? (5)

Answer 57

membrane defects abnormal haemoglobin sickle cell anaemia enzyme deficiency glucose-6-phosphate dehydrogenase deficiency

Question 58

what is extrinsic haemolytic anaemia?

Answer 58

haemolytic anaemia that is acquired. Could be caused by drugs, immune-mediated causes.