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Haemopoiesis Flashcards

1
Q

Where is bone marrow found in an adult?

A 
Pelvis
Sternum
Skull
Ribs
Vertebrae
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2
Q

Where is bone marrow found in an infant?

A

Throughout the skeleton

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3
Q

How is bone marrow obtained?

A 
Trephine biopsy (aspiration of bone marrow, rarely done now)
GCSF mobilised stem cells in the peripheral blood, collected by leucopharesis
Umbilical cord stem cells at time of normal delivery
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4
Q

Which hormone controls differentiation of HPSCs into common myeloid progenitors?

A

Interleukin-3

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5
Q

Which adult tissue/cell has the greatest power of self-renewal?

A

Haemopoietic stem cell

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6
Q

What can HSPC’s do?

A

Self-renewal
Differentiate into variety of specialised cells
Mobilise out of bone marrow into circulating blood
Apoptosis

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7
Q

What are the phagocytic cells?

A 
Monocytes
Macrophages
Kupffer cells
Tissue histiocytes
Microglial cells in CNS
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8
Q

What is the reticuloendothelial system?

A

Part of the immune system, made up of a network of tissue and cells which contain phagocytic cells
Can identify and mount an appropriate immune response to foreign antigens
Main organs are spleen and liver
Extra cellular fluid travels via lymphatics to the lymph nodes
Eg. Since all blood passes through the spleen, the RES cells in the spleen can dispose of damaged or old red blood cells

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9
Q

What makes up the spleen?

A

Red pulp (sinuses lined by endothelial macrophages and cords) and white pulp (similar structure to lymphoid follicles)

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10
Q

How do different cells move through the spleen?

A

Blood enters through the splenic artery
White cells and plasma preferentially pass through the white pulp
Red cells preferentially pass through the red pulp

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11
Q

What are the functions of the spleen in adults?

A

Sequestration and phagocytosis (old/abnormal red cells removed by macrophages)
Blood pooling

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12
Q

What is the name of a condition where the spleen is abnormally large?

A

Splenomegaly

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13
Q

How do you palpate a patient to diagnose an enlarged spleen?

A

Start in Right Lower Quadrant, move towards costal margin after exhalation
It is never normal to palpate the spleen below the costal margin - splenomegaly
The spleen should move towards hand upon inspiration
Measure in cm from costal margin in mid-clavicular line

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14
Q

What are the possible causes of splenomegaly?

A

Back pressure (portal hypertension in liver disease)
Over working red pulp
Over working white pulp
Reverting to foetal function (extramedullary haemopoiesis)
Infiltration by cells that shouldn’t be there (blood cancer eg leukaemia, other cancer metastases)
Infiltration by other material (Gaucher’s disease, sarcoidosis)

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15
Q

What does Gaucher’s disease do to the spleen and liver?

A

Enlarges it

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16
Q

What could cause massive splenomegaly?

A

Chronic myeloid leukaemia, myelofibrosis, malaria, schistosomiasis

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17
Q

What could cause moderate splenomegaly?

A

Chronic myeloid leukaemia, myelofibrosis, malaria, schistosomiasis

Plus, lymphoma, leukaemia, myeloproliferative disorders, liver cirrhosis with portal hypertension, infections such as Glandular fever caused by EBV

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18
Q

What could cause mild splenomegaly?

A

Chronic myeloid leukaemia, myelofibrosis, malaria, schistosomiasis

Plus, lymphoma, leukaemia, myeloproliferative disorders, liver cirrhosis with portal hypertension, infections such as Glandular fever caused by EBV

Plus, infections such as infectious hepatitis, endocarditis, infiltrative disorders such as sarcoidosis, autoimmune diseases such as AIHA, ITP, SLE

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19
Q

What is hypersplenism?

A

Overactive spleen

Results in low blood counts due to pooling of blood in an enlarged spleen

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20
Q

What are the risks associated with having an enlarged spleen?

A

Hypersplenism
Risk of rupture if enlarged and no longer protected by rib cage
If ruptured, can lead to a haematoma in the capsule around the spleen, leading to hypovolaemia and even death
Infarction, as when spleen enlarges its tissues get squashed and so don’t get enough oxygen, leading to tissue death

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21
Q

What is hyposplenism?

A

Underactive spleen

Lack of functioning splenic tissue

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22
Q

What can cause hyposplenism?

A

Splenectomy
Sickle cell disease (typically not in young children)
Coeliac disease

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23
Q

What are Howell Jolly bodies?

A

DNA remnants in erythrocytes

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24
Q

How can a blood film show an underachieve spleen?

A

Hyposplenia can be seen if Howell Jolly bodies are present (DNA remnants in erythrocytes). They look like normal RBCs but have a little black dot inside.

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25
Q

Why is hyposplenism so dangerous?

A

It puts patients at very high risk of sepsis, especially from encapsulated organisms eg. Pneumococcus, Haemophilus influenzae, Meningococcus
If patients have an underactive they are put on prophylactic penicillin for the rest of their lives, eg. if they have sickle cell disease

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26
Q

What is the normal RBC count?

A

4.4 - 5.9 x10^12 /l

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27
Q

What is the normal Hb value?

A

13.5 - 16.7 g/dl

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28
Q

What is the normal Mean Corpuscular Volume (MCV) value and what does it mean?

A

80 - 100 fl

The size of the RBCs

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29
Q

What are the functions of RBCs?

A 
Deliver oxygen to the tissues
Carry haemoglobin
Maintain haemoglobin in its reduced (ferrous) state
Maintain osmotic equilibrium
Generate energy
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30
Q

How is haemoglobin synthesised?

A

Globin chains (from chromosomes 11 and 16) are synthesised independently and combined to form different Hbs

31
Q

When does the switch from foetal to adult Hb occur?

A

3-6 months of age

32
Q

What is haemolytic anaemia?

A

Abnormal breaking down of RBCs, either intravascular or extravascular (usually the spleen)
Can be due to changes in components of cell membrane, changing cell shape, making it more easily broken down and less deformable, so spleen recognises cell as ‘abnormal’
Red cell survival reduces below 120 days, causing anaemia

33
Q

How do the kidneys deal with anaemia?

A

Anaemia cause reduced pO2, detected in the interstitial peritubular cells in the kidney
Increased production of Erythropoietin by the kidney
Erythropoietin stimulates maturation and release of RBCs from marrow
Number of RBCs increased and so Hb rises
More oxygen can be delivered
Via feedback loop, erythropoietin production falls

34
Q

How is haemoglobin catabolised?

A

Hb -> Bilirubin (-> liver -> bile duct -> small intestine -> large intestine ->…)
Eventually go to kidneys, then get excreted as urobilinogen

35
Q

What can an excess of RBC destruction cause?

A

Haemolytic anaemia

Jaundice (due to excess bilirubin formation from broken down heme groups)

36
Q

What is cytopenia?

A

Reduction in number of RBCs

37
Q

What is the name for low RBC count?

A

Anaemia

38
Q

What is the name for low WBC count?

A

Leucopenia

39
Q

What is the name for low neutrophil count?

A

Neutropenia

40
Q

What is the name for low platelet count?

A

Thrombocytopenia

41
Q

What is the name for low RBC, WBC and platelet count?

A

Pancytopenia

42
Q

What is the name for high RBC count?

A

Erythrocytosis

43
Q

What is the name for high WBC count?

A

Leucocytosis

44
Q

What is the name for high neutrophil count?

A

Neutrophilia

45
Q

What is the name for high platelet count?

A

Thrombocytosis

46
Q

What is the name for high lymphocyte count?

A

Lymphocytosis

47
Q

What are neutrophils?

A

First-responder phagocytes, the commonest white cell,

essential part of innate immune system

48
Q

How long can neutrophils live in the bloodstream once mature?

A

1 - 4 days

49
Q

What is neutrophil maturation controlled by? What does it do?

A 
G-CSF
Increases production of neutrophils
Decreases time taken to release mature
cells from BM
Enhances chemotaxis
Enhances phagocytosis and killing of pathogens
50
Q

How do you treat a patient with neutropenia and sepsis?

A

Recombinant G-CSF
(means manufactured)
Patients can self inject that to reduce neutropenic infections post-chemotherapy

51
Q

What is the main cause of neutrophilia?

A

Infection

52
Q

What can cause neutrophilia?

A 
INFECTION
Tissue damage
Acute inflammation
Cancer
Cytokines eg. G-CSF
Metabolic/endocrine disorders
Smoking
Myeloproliferative diseases
Acute haemorrhage
Drugs eg. steroids
53
Q

What range of neutrophil count would diagnose neutropenia?

A

<1.5 x10^9 /L

Severe if <0.5 x10^9 /L

54
Q

What can cause neutropenia?

A

Increased removal or use (from immune destruction, sepsis, splenic pooling)
Reduced production
Benign ethnic neutropenia
Cyclic neutropenia

55
Q

What can cause reduced production of neutrophils?

A

B12/folate deficiency - building blocks
Infiltration of bone marrow by malignancy or fibrosis - no room
Aplastic anaemia - empty marrow, no precursors
Radiation - mature cells killed, precursors stunned
Drugs - chemotherapy, antibiotics, anti-epileptics, psychotropic drugs, DMARDs, Rituximab - poison the marrow
Viral infection - very common - temporarily sick
Congenital disorders - not working properly from birth

56
Q

What can neutropenia cause?

A 
Severe life threatening bacterial or fungal infection
Mucosal ulceration (eg. mouth)
Neutropenic sepsis (EMERGENCY - IV antibiotics given immediately)
57
Q

What do monocytes do?

A

Respond to inflammation and antigenic stimuli
Migrate to tissues where they become macrophages
Contain lysosomes for digestion
Phagocytosis and pinocytosis

58
Q

What do lysosomes contain?

A

Lysozyme, complement, interleukins, arachidonic acid, CSF

59
Q

What causes monocytosis?

A

Chronic inflammatory condition (RA, SLE, Crohn’s, UC)
Chronic infection eg TB
Carcinoma
Myeloproliferative disorders/ leukaemias (CMML, aCML, JMML, AML)

60
Q

How long do eosinophils circulate in the bloodstream? How long do they live?

A

3-8 hours

8-12 days

61
Q

What do eosinophils do?

A

Responsible for dealing with some parasites
Mediator of allergic response
Migrate to epithelial surfaces
Contain granules
Phagocytosis of antigen - antibody complexes
Mediate hypersensitivity reactions

62
Q

What do eosinophilic granules contain?

A

Arginine, Phospholipids, enzymes

63
Q

What are some causes of eosinophilia?

A 
Allergies
Drug hypersensitivity
Churg-Strauss
Parasitic infection
Skin diseases
Hodgkin Lymphoma
Acute lymphoblastic leukaemia
Acute myeloid leukaemia
Myeloproliferative conditions
Eosinophilic leukaemia
Idiopathic hypereosinophilic syndrome
64
Q

Which WBC is the largest and least common?

A

Basophil

65
Q

What do basophils do?

A

Active in allergic reactions and inflammatory conditions

Contain dense granules

66
Q

What do the granules of basophils contain?

A

Histamine, heparin, hyaluronic acid, serotonin

67
Q

Where do lymphocytes originate?

A

In the bone marrow

68
Q

What are the three lymphocytes?

A

B cells
T cells
Natural Killer cells

69
Q

What are some reactive causes of lymphocytosis?

A 
Viral infections
Bacterial infections (esp. whooping cough)
Stress related (MI)
Post splenectomy
Smoking
70
Q

What are some reactive causes of basophilia?

A

Immediate hypersensitivity reactions, ulcerative collitis, rheumatoid arthritis

71
Q

What are some myeloproliferative causes of basophilia?

A

CML, MPN (ET/PRV/MF), systemic mastocytosis

72
Q

What are some lymphoproliferative (malignant) causes of lymphocytosis?

A

Chronic Lymphocytic leukaemia (B cells)
T or NK cell leukaemia
Lymphoma (cells ‘spill’ out of infiltrated bone marrow)

73
Q

What is pancytopenia?

A

Reduction in all cells; RBC’s, WBC’s, and platelets

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