Lecture 6 - Haemopoiesis Flashcards
Where does haemopoiesis occur in an adult?
- Bone marrow
- Axial skeleton in an adult: pelvis, sternum, ribs, vertebrae
- In neonates: entire skeleton
Where is erythropoietin and thrombopoietin secreted from? What is their function?
- Erytropoietin secreted by kidney stimulates RBC prod.
- Thrombopoietin secreted by liver and kidney stimulate platelet prod
What is the Reticuloendothelial system? Main organs? Function?
- Part of immune system, made up of monocytes in the blood
[Kupffer cell in liver, microglial in CNS, langerhans in skin] - Major organ is spleen and liver
- Function: remove dead/dmg cells and destroy foreign antigens
Function of the spleen in adults
- Phagocytosis of old RBC
- Blood pooling: platelets n RBC rapidly mobilised during bleeding
- Extramedullary haemopoiesis: pluripotent stem cells proliferate when bone marrow fails (myelofibrosis)
- Immune function: contain B and T cells
Diff of white and red pulp in spleen
- Red pulp: red cells pass thru, identify old RBC
- White pulp: WBC & plasma pass thru, stimulate immune response
Causes of splenomegaly
- Portal hypertension in liver disease (reduced blood flow to liver –> build up in spleen)
- Overwork
- Extramedullary haemopoiesis
- Cancer metastasised
- Granuloma (tiny cancer)
Splenomegaly can be categorised into diff. ranges (massive –> mild) give one eg of each. What can splenomegaly cause?
- Massive: myelofibrosis & chronic myeloid leukemia (result in extramedullary haemopoiesis) or malaria
- Moderate: lymphoma, liver cirrhosis w portal hypertension, glandular fever
- Mild: infection, endocarditis (inflammation of heart chamber valves)
- Splenomegaly can be subset of hypersplenism –> low blood count due to pooling of blood
- Spleen high vascular –> rupture –> death by exsanguination –> avoid contact sports
What are the causes of hyposplenism?
- Splenectomy (due to splenic trauma/cancer)
- Sickle cell disease
- GI disease (Chron’s/coeliac)
- Autoimmune disease (RA, Hashimoto, systemic lupus)
Presence of what in blood confirms hyposplenism? What are patients with this condition at risk of? What should be done to reduce the risk?
- Howell Jolly bodies: RBC w DNA remnants
- Will normally be removed by fully functioning spleen
- Risk of sepsis from encapsulated bac. (streptococcus pneumonia/meningococcus) –> immunised and lifelong prophylactic antibiotics
Function and structure of RBC
- Function: deliver O2 to tissue, maintain Hb in reduced (ferrous) state
- Biconcave, no nucleus, no mitochondria, no DNA
- 2α, 2β globin chains (Ch 11 & 16)
What do changes in RBC membrane structure result in?
- RBC less deformable/more fragile
- Removed by spleen –> haemolytic anaemia
What are the proteins involved in hereditary spherocytosis? Mode of inheritance? And their functions?
- Spherocytosis is due to mutation in one of the proteins
- Autosomal dom.
Say Anything Before Popping
1. Spectrin: actin crosslinking (most common)
2. Ankyrin: links integral membrane proteins to spectrin-actin cytoskeleton
3. Band 3: facilitates chloride and bicarbonate exchange across membrane
4. Protein 4.2: ATP-binding protein regulate association of band 3 w ankyrin
What are neutrophils (func. and structure)? What hormone controls their maturation from myeloblast?
- Most common phagocyte, part of immune system
- Has 3-5 lobed nuclei
- Maturation controlled by hormone G-CSF (glycoprotein growth factor and cytokine):
1. Increases prod. of neutrophils
2. Speeds up release of mature N from BM
3. ⬆️phagocytosis and chemotaxis
How is recombinant G-CSF used clinically?
- Controls neutrophil growth
- Administered to patins when more neutrophils are needed: neutropenia/sepsis (AFTER CHEMOTHERAPY)
What is neutrophilia and its causes?
- Increase in no. of circulating neutrophils
- Caused by: infection, tissue dmg, myeloproliferative diseases, cytokines (G-CSF), haemorrhage (decrease in overall blood vol, ⬆️circulating WBC)