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Semester 2 MEH > L5: Heamopoises, Spleen and Bone Marrow > Flashcards

L5: Heamopoises, Spleen and Bone Marrow Flashcards

1
Q

What is haemopoiesis?

A

Production of blood cells and platelets that occurs in the bone marrow

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2
Q

What is the difference in distribution of bone marrow between children and adults?

A

Extensive in children

Limited to axial skeleton in adults –> sternum, ribs, pelvis, skull, vertebrae

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3
Q

What is the name of the process for sampling bone marrow?

A

Trephine biopsy

Into pelvis

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4
Q

What are the 5 major pathways that take place in the bone marrow? What cells do they produce?

A

1) Erythropoesis–> erythrocytes (RBCs)
2) Granulopoesis–> granulocytes –> neutrophils, basophils and eosinophils
3) Thrombopoesis –> Platelets
4) Monocytopoiesis –> monocytes
5) Lymphopoiesis –> lymphocytes T and B

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5
Q

What are the important hormones involved in HPSC differentiation?

A

Erythropoietin –> kidney –> RBC production
Thrombopoietin –> Liver –> platelets
G-CSF (granulocyte colony stimulating factor)
Interleukins

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6
Q

What is the common cells they all originate from?

A

Multipotential hematopoietic stem cell

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7
Q

What causes the stem cells to differentiate?

A

Hormones
Transcription factors
Interaction with non-haemopoietic stem cells e.g. endothelial cells

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8
Q

What are the characteristics haemopoietic stem cells?

A
  • ->Self renewal
  • -> Differentiate into specialised cells –> right signal
  • -> Pathological condition –> extramedullary hematopoiesis –> circulate blood to colonise different structures/tissues
  • -> Sign of pathology –> bone under stress
  • -> HPSC transplant mainstream haematological procedure
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9
Q

Where can HPSC be obtained from?

A

Bone marrow
GCSF mobilised peripheral stem cells (leucopharesis- removal procedure)
Umbilical cord–> cord bank

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10
Q

What is the reticuloendothelial system (RES)?

A 
Part of immune system
Monocytes in blood 
Tissues containing phagocytic cells 
--> Liver --> kupffer cell
--> Connective tissue --> tissue histiocyte
--> CNS --> microglia
--> Peritoneal cavity --> Peritoneal macrophage
--> Spleen --> Red pulp macrophage
--> Skin and mucosa --> Langerhan cells
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11
Q

What is the role of the reticulendothelial system?

A

Remove dead or damaged cells

Remove foreign pathogens

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12
Q

What are the main organs in the reticuloendothelial system?

A

Spleen and liver

Spleen –> removes old/damaged erythrocytes

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13
Q

What are the two different tissues found in the spleen ?

A

Red pulp–> sinuses lined endothelial macrophages and cords –> heamatopoeitic function
White pulp –> Similar structure to lymphoid follicles –> immune function

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14
Q

What is the main function of the spleen in adults?

A

1- Sequestration and phagocytosis of old/damaged RBC
2- Blood pooling –> rapidly mobilised during bleeding
3- Extramedullary haemopoiesis–> pluripotent stem cells proliferate–> haematological stress or bone marrow failure
4- Immunological function –> 25% T cells, 15% B cells

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15
Q

How does blood enter the spleen?

A

Splenic artery
Immune cells and plasma –> white pulp
Blood cells –> Red pulp

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16
Q

What does splenomegaly mean?

A

Enlarged spleen

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17
Q

Why does splenomegaly occur?

A

Back pressure –> portal hypertension
Over work –> red or white pulp
Extramedullary haemopoiesis
Infiltration of cells –> cancer cells blood origin or metastases
Infiltration of other material –> sarcoidosis (granulomas, abnormal infiltration of immune cells)

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18
Q

How would you perform an examination of the spleen?

A

Not normally palpable
Start in right illiac fossa–> large spleen maybe missed if only palpate the left
Inspiration–> edge of spleen maybe felt
Splenic notch –>
Measure in cm from costal margin in mid-clavicular line

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19
Q

What are two of the clinical consequences of an enlarged spleen?

A

Hypersplenism –> pooling of blood–> low blood count

Rupture –> enlarged not protected by ribs –> damaged

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20
Q

What can cause splenomegaly?

A 
Lot of things!!
Massive --> chronic myeloid leukaemia
--> myelofibrosis, malaria, schistosomiasis
Moderate --> lymphoma
--> leukaemias 
--> Myeloproliferative disorders 
--> Infections --> glandular fever
--> Liver cirrhosis with portal hypertension
Mild --> infectious hepatitis 
--> endocarditis
--> autoimmune disease
--> infiltrative disorders- sarcoidosis
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21
Q

What is hyposplenism?

A

Lack of functioning of splenic tissue

22
Q

How can hyposplenism be detected?

A

Howell Jolly bodies –> DNA remnants

Spleen would normally remove

23
Q

What are the causes of hyposplenism?

A

Splenectomy
Sickle cell disease–> multiple infarcts and fibrosis
Gastrointestinal diseases
Autoimmune disorders

24
Q

What is an essential function of the spleen? What happens if this doesn’t happen? How is it avoided?

A

Removal of encapsulated bacteria
Sepsis
Patients are immunised, and given lifelong antibiotic prophylaxis

25
Q

What are erthrocytes? What is the function?

A

RBC–> biconcave, no nucleus, no (few mitochondria), ↑SA, lifepan 120 days

  • Delivery of O2
  • Removal of CO2
  • Maintain haemoglobin in reduced state
  • Maintain osmotic equilibrium
  • Generate energy
26
Q

What is haemoglobin?

A

Tetramere of 2 pairs of globin chain–> own haem group

Globin gene on Ch11 and 16

27
Q

What is an important regulator of oxygen binding in heamoglobin?

A

2,3- Bisphophoglycerate
Binds to the centre of the molecule and reduces the affinity for oxygen making it easier to release it at the target tissues

28
Q

What is the difference between fetal and adult heamoglobin?

A

Fetal- two alpha and two gamma chains –> ↑ affinity for O2
Adult- two alpha and two beta chains
Switches at 3-6 months

29
Q

What is the structure of RBC membrane? What is special about it?

A

Band 3–> integral membrane protein –> links cytoskeleton to membrane and facilitates chloride and bicarbonate exchange
Protien 4.2–> ATP binding–> attaches ankyrin to band 3
Ankyrin –> link membrane protein to spectrin-actin cytoskeleton
Spectrin –> actin crosslinking, scaffold protein, links actin cytoskeleton to membrane parallel to plasma membrane
Special–> flexible, allows RBC to change shape to pass through capillary wall

30
Q

What happens if the plasma membrane of RBC is changes?

A

Fragile cells, less deformable, abnormal shape, cannot pass through capillary wall
Heamolytic anaemias –> Hereditary spectrocytosis and hereditary ellipotocytosis
Spleen recognises and removes

31
Q

What happens to old or damaged RBC?

A

Engulfed by macrophages in RES
Haem–> Fe2+ recycled
Bilirubin –> unconjuguated –> bound to albumin
Liver–> conjugated with glucaronic acid –> bilirubin diglucoronide
Bile –> duodenum

32
Q

What happens to bile in the intestines?

A

Bacteria–> Glucaronic acid removed
Bilirubin converted to Urobilinogen
Oxidised–> stercobilin in feaces (brown)
Some Urobilinogen –>blood–> kidney –> oxidised–> Urobilin–> excreted in urine (yellow)

33
Q

What happens if unconjugated bilirubin accumulates?

A

Jaundice

34
Q

What word mean reduction in number of blood cells?

A

Cytopenia

35
Q

What suffix’s mean increase in number of blood cells?

A

…cytosis
OR
…philia

36
Q

What are neutrophils?

A 
Subtype of WBC
First responders
Nucleus multiple segment 3-5
Essential part of innate immune system
Circulate bloodstream
Invade tissues 
Live for 14days
37
Q

What is responsible for neutrophil maturation?

A

Myelocyte
G-CSF–> glycoprotein GF and cytokine which:
–> ↑ neutrophil production
–> speeds up release of mature cells from BM
–> Enhances chemotaxis
–> Enhances phagocytosis and killing of pathogens

38
Q

When is G-CSF used therapeutically?

A

More neutrophils needed

Severe neutropenia after chemotherapy

39
Q

What does neutrophilia mean? Why?

A 
Increase in number of circulating neutrophils
Lots of causes;
- infection 
- myloproliferative disease
- tissue damage 
- smoking 
- drugs 
- acute inflammation 
- cytomines (G-CSF) 
- metabolic disorders
- cancer
- endocrine disorders
- acute haemorrhage
40
Q

What is the difference between the marginated pool and circulating pool of neutrophils? What does a haemorrhage do?

A

Marginated –> neutrophils adhered to endothelium of capillaries
Circulating–> neutrophils free to move throughout the circulation
Brings more cells out of the marginated pool

41
Q

What is neutropenia?

A

Low neutrophil count

42
Q

What are consequences of neutropenia?

A

Severe life threatening bacteria infection or fungal infection
Mucosal ulceration
Neutropenic sepsis = medical emergancy

43
Q

What are the causes of neutropenia?

A

Reduced production of neutrophil due to:
1. B12/ folate deficiency
2. Aplastic anaemia (empty marrow)
3. Viral infection
4. Congential
5. Infiltration (maliginancy or fibrosis in spleen no room for neutrophil production)
6. Radiation –> mature cells killed, precusors stunned
7. Drugs –> chemotherapy, antibiotics, anti-epiletics… poison marrow and inhibit blood cell production
OR
Increased removal
1. Immune destruction –> autoantibodies
2. Sepsis –> rapid migration into tissue, synthesis lagging
3. Splenic pooling–> sequestration in spleen

44
Q

What are monocytes?

A
  • Largest cells
  • Circulate (1-3 days)–> migrate –> differentiate into macrophages or dendritic cells
  • Phagocytose debris/ microorgansisms
  • Antigen presenting role
  • Defence agaist chronic bacterial infections
45
Q

What is monocytosis? What causes it?

A

Increased circulating number

  • Bacterial infection
  • Inflammatory conditions
  • Carcinoma
  • Myeloproliferative disorders and leukaemias
46
Q

What are eosinophils?

A

Subtype of WBC
Parasitic worms (helminths) and allergic response mediator
Granules–> Cytotoxic proteins–> Eosinophil cationic proteins and elastase
Phagocytosis antigen-antibody complexes
Innappropiate activation –> tissue damage and inflammation

47
Q

What is eosinophilia? What causes it?

A

Increased eosinophils
Common–> allergic disease, parasite infection, drug hypersensitivity, Chrug-Strauss (autoimmune condition inflammation of small BV), Skin diseases
Rare–> Hodgkin lymphoma, leukaemias (various), myeloproliferative conditions

48
Q

What are basophils?

A

Least common and large
<1% of leukocyes
Active in allergic reactions and inflammatory conditions
Large dense granules –> histamine, heparin, hyaluronic acids, serotonin
Stain deep blue-purple

49
Q

What is basophilia? Why?

A

Increased numbers
Reactive–> immediate hypersensitivity reactions, immune disorders- ulcerative collitis and rheumatoid arthritis
Myeloproliferative –> systemic mastocytosis

50
Q

What are lymphocytes?

A

Originate in bone marrow
B–> humoral immunity, antibody forming cells
T–> cellular immunity
natural killer cells (cell mediated cytotoxicity)

51
Q

What is lymphocytosis? Why?

A

Increased numbers
Reactive–> viral/bacterial infections, stress related (MI), post splenectomy, smoking
Lymphoproliferative –> malignant–> chronic lymphocytic leukaemeia, T or NK cell leukaemia, lymphoma

Semester 2 MEH (23 decks)

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