MEH 5 - Haemopoiesis, the Spleen + Bone Marrow Flashcards
What is haemopoiesis?
Where is bone marrow found in infants + adults?
- The production of blood cells that occurs in bone marrow
- Bone marrow is extensive throughout the body in infants, but more limited in adults - usually within the axial skeleton, e.g.: pelvis, sternum, skull, ribs + verterbrae.
What do the 5 major blood cells differentiate from?
What is this differentiation determined by?
- 5 lineages arise from haemopoietic stem cells
(HPSC’s) in bone marrow, which can become common myeloid or lymphoid progenitors. - Differentiation is determined by hormones, transcription factors + interaction w/non-haemopoietic cell types
- Erythropoietin secreted by kidney stimulates RBC production
- Thrombopoietin secreted by liver and kidney stimulates production of platelets.
NB: the major 5 are platelets, eosinophils, basophils, neutrophils + monocytes.
What are the key features of HPSC’s?
What are the major sources of HPSC’s?
- Capable of self renewal, can differentiate into variety of specialised cells with correct stimuli, can mobilise into blood and colonise other tissues in pathological conditions (extra-medullary haemopoiesis).
- Bone marrow aspiration (rare), leucopharesis + umbilical cord stem cell banks.
NB: HPSC transplantation now mainstream procedure.
What is the reticuloendothelial system (RES)?
What is its role?
- Part of the immune system made up of monocytes in blood and a network of phagocytic cells in tissues. Main organs are the spleen and liver.
- To remove dead/damaged cells + identify/destroy foreign antigens.
- RES cells in spleen dispose of red blood cells (120 days old or damaged).
What are the 4 main functions of the spleen in adults?
How does blood enter the spleen?
1) Sequestration + phagocytosis - of old/abmormal RBC’s via macrophages
2) Blood pooling - of platelets and RBC’s which are rapidly mobilised upon bleeding
3) Extramedullary haemopoiesis - stem cells proliferate during haematological stress or if marrow fails
4) Immunological function - 25% T-cells and 15% B-cells found in spleen
- Blood enters via splenic artery
- White cells + plasma pass through white pulp
- Red cells pass through red pulp
Why does splenomegaly occur?
How is the spleen examined clinically?
- Back pressure due to portal hypertension in liver disease, expansion due to infiltrating cells (e.g.: cancer cells) or other materials (e.g.: granulomas) or over work of red/white pulp.
- Spleen should never be palpable below costal margin. Start to palpate in right iliac fossa. Feel for spleen/splenic notch on inspiration
What are the 3 types of splenomegaly and their causes?
What are the potential consequences?
1) Mild - infections, autoimmune diseases
2) Moderate - lymphoma, leukaemia, infections
3) Massive - myelofibrosis, chronic myeloid leukemia, malaria
- Hypersplenism (low blood counts due to pooling of blood in enlarged spleen)
- Significant risk of rupture as spleen no longer protected by rib cage (avoid contact sport and rigorous activity).
What is hyposplenism?
What are the 4 main causes?
What are patients with hyposplenism at high risk of?
- Hyposplenism is a lack of functioning splenic tissue (either not having a spleen or its not functioning)
- 1) Splenectomy (e.g.: after rupture or cancer) 2) Sickle cell disease (due to fibrosis) 3) GI diseases (e.g.: coeliacs) + 4) Autoimmune disorders (e.g.: rheumatoid arthritis).
- Patients w/hyposplenism at high risk of sepsis from encapsulated bacteria (e.g.: streptococcus pneumoniae) - must be immunised and given long life antibiotic prophylaxis.
How do RBC’s change their shape?
- Changes in components of cell membrane result in changes in RBC shape.
- Changes to PM cause cells to become less deformable and more fragile.
- Spleen recognises these cells as abnormal and removes them from circulation causing haemolytic anaemia.
How is haem from RBC’s extracted and then degraded in the body?
- Old RBC’s engulfed by macrophages in RES, Fe2+ from haem is recycled.
- Haem broken down into bilirubin, excess unconjugated bilirubin can can cause jaundice.
- Bilirubin taken up by liver + conjugated with glucoronic acid to make bilirubin digluconoride.
- This is secreted in bile into duodenum, glucoronic acid removed by bacteria. Bilirubin converted to urobilinogen which is oxidised into stercobilin. Stercobilin removed in faeces (causes brown colour)
- Some urobilinogen absorbed into blood + taken to kidney, oxidised to urobilin and excreted as urine (causes yellow colour)
What are the suffix’s added for cells when there is an increase or decrease in cell count?
- Cytosis/philia = increase (e.g.: lymphocytosis or basophilia)
- Penia/aemia = decrease (e.g.: anaemia or neutropenia)
What is the role of neutrophils?
How is maturation controlled?
- Neutrophils are first-responder phagocytes, part of innate immune system + invade tissues for 1-4 days.
- Maturation controlled by G-CSF - increases production of neutrophils, speeds up release of mature cells from bone marrow, enhances chemotaxis + phagocytosis.
- G-CSF (recombinant) administered in patients with severe neutropenia or sepsis after chemotherapy.
What is neutrophilia?
What are the potential causes?
- An increase in the number of circulating neutrophils
- Infection, myeloproliferative diseases, cytokines such as G-CSF + acute haemorrhage.
What is neutropenia?
What are the main causes?
What are the consequences?
- A neutrophil count under 1.5 x 10^9/L
- Either caused by reduced production (e.g.: B12/folate deficiency, radiation, drugs, viral infection etc) or by increased removal or use (immune destruction, sepsis, splenic pooling etc)
- Bacterial and fungal infections can be life-threatening, can also get mucosal ulceration (painful mouth ulcers)
- Neutropenic sepsis is a medical emergency - I.V AB’s given immediately.
What is the role of monocytes?
What are the causes of monocytosis?
- Largest cells in blood, circulate for 1-3 days before migrating to tissues + differentiating into macrophages.
- Phagocytose organism + present antigens
- Monocytosis (increase in number) caused by bacterial infections, inflammatory conditions, carcinoma + myeloproliferative disorders.
