L5: Heamopoises, Spleen and Bone Marrow Flashcards
What is haemopoiesis?
Production of blood cells and platelets that occurs in the bone marrow
What is the difference in distribution of bone marrow between children and adults?
Extensive in children
Limited to axial skeleton in adults –> sternum, ribs, pelvis, skull, vertebrae
What is the name of the process for sampling bone marrow?
Trephine biopsy
Into pelvis
What are the 5 major pathways that take place in the bone marrow? What cells do they produce?
1) Erythropoesis–> erythrocytes (RBCs)
2) Granulopoesis–> granulocytes –> neutrophils, basophils and eosinophils
3) Thrombopoesis –> Platelets
4) Monocytopoiesis –> monocytes
5) Lymphopoiesis –> lymphocytes T and B
What are the important hormones involved in HPSC differentiation?
Erythropoietin –> kidney –> RBC production
Thrombopoietin –> Liver –> platelets
G-CSF (granulocyte colony stimulating factor)
Interleukins
What is the common cells they all originate from?
Multipotential hematopoietic stem cell
What causes the stem cells to differentiate?
Hormones
Transcription factors
Interaction with non-haemopoietic stem cells e.g. endothelial cells
What are the characteristics haemopoietic stem cells?
- ->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
Where can HPSC be obtained from?
Bone marrow
GCSF mobilised peripheral stem cells (leucopharesis- removal procedure)
Umbilical cord–> cord bank
What is the reticuloendothelial system (RES)?
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
What is the role of the reticulendothelial system?
Remove dead or damaged cells
Remove foreign pathogens
What are the main organs in the reticuloendothelial system?
Spleen and liver
Spleen –> removes old/damaged erythrocytes
What are the two different tissues found in the spleen ?
Red pulp–> sinuses lined endothelial macrophages and cords –> heamatopoeitic function
White pulp –> Similar structure to lymphoid follicles –> immune function
What is the main function of the spleen in adults?
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
How does blood enter the spleen?
Splenic artery
Immune cells and plasma –> white pulp
Blood cells –> Red pulp
What does splenomegaly mean?
Enlarged spleen
Why does splenomegaly occur?
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)
How would you perform an examination of the spleen?
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
What are two of the clinical consequences of an enlarged spleen?
Hypersplenism –> pooling of blood–> low blood count
Rupture –> enlarged not protected by ribs –> damaged
What can cause splenomegaly?
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
What is hyposplenism?
Lack of functioning of splenic tissue
How can hyposplenism be detected?
Howell Jolly bodies –> DNA remnants
Spleen would normally remove
What are the causes of hyposplenism?
Splenectomy
Sickle cell disease–> multiple infarcts and fibrosis
Gastrointestinal diseases
Autoimmune disorders
What is an essential function of the spleen? What happens if this doesn’t happen? How is it avoided?
Removal of encapsulated bacteria
Sepsis
Patients are immunised, and given lifelong antibiotic prophylaxis
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
What is haemoglobin?
Tetramere of 2 pairs of globin chain–> own haem group
Globin gene on Ch11 and 16
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
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
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
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
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
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)
What happens if unconjugated bilirubin accumulates?
Jaundice
What word mean reduction in number of blood cells?
Cytopenia
What suffix’s mean increase in number of blood cells?
…cytosis
OR
…philia
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
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
When is G-CSF used therapeutically?
More neutrophils needed
Severe neutropenia after chemotherapy
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
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
What is neutropenia?
Low neutrophil count
What are consequences of neutropenia?
Severe life threatening bacteria infection or fungal infection
Mucosal ulceration
Neutropenic sepsis = medical emergancy
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
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
What is monocytosis? What causes it?
Increased circulating number
- Bacterial infection
- Inflammatory conditions
- Carcinoma
- Myeloproliferative disorders and leukaemias
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
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
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
What is basophilia? Why?
Increased numbers
Reactive–> immediate hypersensitivity reactions, immune disorders- ulcerative collitis and rheumatoid arthritis
Myeloproliferative –> systemic mastocytosis
What are lymphocytes?
Originate in bone marrow
B–> humoral immunity, antibody forming cells
T–> cellular immunity
natural killer cells (cell mediated cytotoxicity)
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
