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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
Why is hyposplenism so dangerous?
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
26
What is the normal RBC count?
4.4 - 5.9 x10^12 /l
27
What is the normal Hb value?
13.5 - 16.7 g/dl
28
What is the normal Mean Corpuscular Volume (MCV) value and what does it mean?
80 - 100 fl | The size of the RBCs
29
What are the functions of RBCs?
``` Deliver oxygen to the tissues Carry haemoglobin Maintain haemoglobin in its reduced (ferrous) state Maintain osmotic equilibrium Generate energy ```
30
How is haemoglobin synthesised?
Globin chains (from chromosomes 11 and 16) are synthesised independently and combined to form different Hbs
31
When does the switch from foetal to adult Hb occur?
3-6 months of age
32
What is haemolytic anaemia?
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
How do the kidneys deal with anaemia?
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
How is haemoglobin catabolised?
Hb -> Bilirubin (-> liver -> bile duct -> small intestine -> large intestine ->...) Eventually go to kidneys, then get excreted as urobilinogen
35
What can an excess of RBC destruction cause?
Haemolytic anaemia | Jaundice (due to excess bilirubin formation from broken down heme groups)
36
What is cytopenia?
Reduction in number of RBCs
37
What is the name for low RBC count?
Anaemia
38
What is the name for low WBC count?
Leucopenia
39
What is the name for low neutrophil count?
Neutropenia
40
What is the name for low platelet count?
Thrombocytopenia
41
What is the name for low RBC, WBC and platelet count?
Pancytopenia
42
What is the name for high RBC count?
Erythrocytosis
43
What is the name for high WBC count?
Leucocytosis
44
What is the name for high neutrophil count?
Neutrophilia
45
What is the name for high platelet count?
Thrombocytosis
46
What is the name for high lymphocyte count?
Lymphocytosis
47
What are neutrophils?
First-responder phagocytes, the commonest white cell, | essential part of innate immune system
48
How long can neutrophils live in the bloodstream once mature?
1 - 4 days
49
What is neutrophil maturation controlled by? What does it do?
``` G-CSF Increases production of neutrophils Decreases time taken to release mature cells from BM Enhances chemotaxis Enhances phagocytosis and killing of pathogens ```
50
How do you treat a patient with neutropenia and sepsis?
Recombinant G-CSF (means manufactured) Patients can self inject that to reduce neutropenic infections post-chemotherapy
51
What is the main cause of neutrophilia?
Infection
52
What can cause neutrophilia?
``` INFECTION Tissue damage Acute inflammation Cancer Cytokines eg. G-CSF Metabolic/endocrine disorders Smoking Myeloproliferative diseases Acute haemorrhage Drugs eg. steroids ```
53
What range of neutrophil count would diagnose neutropenia?
<1.5 x10^9 /L | Severe if <0.5 x10^9 /L
54
What can cause neutropenia?
Increased removal or use (from immune destruction, sepsis, splenic pooling) Reduced production Benign ethnic neutropenia Cyclic neutropenia
55
What can cause reduced production of neutrophils?
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
What can neutropenia cause?
``` Severe life threatening bacterial or fungal infection Mucosal ulceration (eg. mouth) Neutropenic sepsis (EMERGENCY - IV antibiotics given immediately) ```
57
What do monocytes do?
Respond to inflammation and antigenic stimuli Migrate to tissues where they become macrophages Contain lysosomes for digestion Phagocytosis and pinocytosis
58
What do lysosomes contain?
Lysozyme, complement, interleukins, arachidonic acid, CSF
59
What causes monocytosis?
Chronic inflammatory condition (RA, SLE, Crohn’s, UC) Chronic infection eg TB Carcinoma Myeloproliferative disorders/ leukaemias (CMML, aCML, JMML, AML)
60
How long do eosinophils circulate in the bloodstream? How long do they live?
3-8 hours | 8-12 days
61
What do eosinophils do?
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
What do eosinophilic granules contain?
Arginine, Phospholipids, enzymes
63
What are some causes of eosinophilia?
``` 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
Which WBC is the largest and least common?
Basophil
65
What do basophils do?
Active in allergic reactions and inflammatory conditions | Contain dense granules
66
What do the granules of basophils contain?
Histamine, heparin, hyaluronic acid, serotonin
67
Where do lymphocytes originate?
In the bone marrow
68
What are the three lymphocytes?
B cells T cells Natural Killer cells
69
What are some reactive causes of lymphocytosis?
``` Viral infections Bacterial infections (esp. whooping cough) Stress related (MI) Post splenectomy Smoking ```
70
What are some reactive causes of basophilia?
Immediate hypersensitivity reactions, ulcerative collitis, rheumatoid arthritis
71
What are some myeloproliferative causes of basophilia?
CML, MPN (ET/PRV/MF), systemic mastocytosis
72
What are some lymphoproliferative (malignant) causes of lymphocytosis?
Chronic Lymphocytic leukaemia (B cells) T or NK cell leukaemia Lymphoma (cells 'spill' out of infiltrated bone marrow)
73
What is pancytopenia?
Reduction in all cells; RBC's, WBC's, and platelets

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