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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
What are erthrocytes? What is the function?
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
What is haemoglobin?
Tetramere of 2 pairs of globin chain--> own haem group | Globin gene on Ch11 and 16
27
What is an important regulator of oxygen binding in heamoglobin?
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
What is the difference between fetal and adult heamoglobin?
Fetal- two alpha and two gamma chains --> ↑ affinity for O2 Adult- two alpha and two beta chains Switches at 3-6 months
29
What is the structure of RBC membrane? What is special about it?
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
What happens if the plasma membrane of RBC is changes?
Fragile cells, less deformable, abnormal shape, cannot pass through capillary wall Heamolytic anaemias --> Hereditary spectrocytosis and hereditary ellipotocytosis Spleen recognises and removes
31
What happens to old or damaged RBC?
Engulfed by macrophages in RES Haem--> Fe2+ recycled Bilirubin --> unconjuguated --> bound to albumin Liver--> conjugated with glucaronic acid --> bilirubin diglucoronide Bile --> duodenum
32
What happens to bile in the intestines?
Bacteria--> Glucaronic acid removed Bilirubin converted to Urobilinogen Oxidised--> stercobilin in feaces (brown) Some Urobilinogen -->blood--> kidney --> oxidised--> Urobilin--> excreted in urine (yellow)
33
What happens if unconjugated bilirubin accumulates?
Jaundice
34
What word mean reduction in number of blood cells?
Cytopenia
35
What suffix's mean increase in number of blood cells?
...cytosis OR ...philia
36
What are neutrophils?
``` Subtype of WBC First responders Nucleus multiple segment 3-5 Essential part of innate immune system Circulate bloodstream Invade tissues Live for 14days ```
37
What is responsible for neutrophil maturation?
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
When is G-CSF used therapeutically?
More neutrophils needed | Severe neutropenia after chemotherapy
39
What does neutrophilia mean? Why?
``` 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
What is the difference between the marginated pool and circulating pool of neutrophils? What does a haemorrhage do?
Marginated --> neutrophils adhered to endothelium of capillaries Circulating--> neutrophils free to move throughout the circulation Brings more cells out of the marginated pool
41
What is neutropenia?
Low neutrophil count
42
What are consequences of neutropenia?
Severe life threatening bacteria infection or fungal infection Mucosal ulceration Neutropenic sepsis = medical emergancy
43
What are the causes of neutropenia?
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
What are monocytes?
- 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
What is monocytosis? What causes it?
Increased circulating number - Bacterial infection - Inflammatory conditions - Carcinoma - Myeloproliferative disorders and leukaemias
46
What are eosinophils?
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
What is eosinophilia? What causes it?
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
What are basophils?
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
What is basophilia? Why?
Increased numbers Reactive--> immediate hypersensitivity reactions, immune disorders- ulcerative collitis and rheumatoid arthritis Myeloproliferative --> systemic mastocytosis
50
What are lymphocytes?
Originate in bone marrow B--> humoral immunity, antibody forming cells T--> cellular immunity natural killer cells (cell mediated cytotoxicity)
51
What is lymphocytosis? Why?
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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