6.1 - Haematology 1 Flashcards
(41 cards)
what is haemopoiesis
the production of blood cells from stem cells
- ie RBCs, platelets, and the majority of WBCs
- aka haematopoiesis
- occurs in bone marrow
- begins from haematopoietic stem cells
- in infants, takes place throughout the skeleton
- in adults, there is a limited distribution (mainly axial skeleton including pelvis, sternum, skull, ribs and vertebrae)
- begins from a single cell type: multipotent haematopoietic stem cell (HPSC)
- production of certain cell types is regulated by various hormones
what are different blood cell production stimulated by
Differentiation is determined by: Hormones, transcription factors, interactions with non-haemopoietic cell types
- RBC production stimulated by erythropoietin (EPO)
- platelet production stimulated by thrombopoietin
- Granulocytes ★ production stimulated by G-CSF
- Lymphocyte production stimulated by interleukins and TNF-α
the HPSCs differentiate into either… common myeloid progenitor cells or common lymphoid progenitor cells… and from them all the other blood cells develop
5 major lineage pathways arise from the haemopoietic stem cells in bone marrow (more detail on other cards)
granulocytes = eosinophils, basophils, neutrophils
what are the 5 main lineage pathways arising from the haemopoietic stem cells in bone marrow
details about each one on seperate cards
- thrombopoiesis (platelet formation)
- monocytopoiesis (macrophage formation)
- lymphopoiesis (T and B-lymphocyte formation)
- granulopoeisis (basophil, neutrophil, eosinophil formation)
- erythropoeisis (RBC formation)
thrombopoeisis
multipotent haemapoietic stem cell (HPSC) → common myeloid progenitor + common lymphoid progenitor → megakarocyte + erythroblast + mast cells + myeloplast → platelets
platelets aka thrombocytes
erythropoeisis
HPSC → common myeloid progenitor + common lymphoid progenitor → erythroblast + megakaryocyte + mast cells + myeloblast → reticulocyte → erythrocyte/RBCs
granulopoeisis
HPSC → common myeloid progenitor + common lymphoid progenitor → myeloblast + mast cell + erythroblast + megakaryocyte → basophil + neutrophil + eosinophils + monocytes
monocytopoeisis
HPSC → common myeloid progenitor + common lymphoid progenitor → myeloblast + mast cell + erythroblast + megakaryocyte → basophil + neutrophil + eosinophils + monocytes → macrophages
lymphoidpoeisis
HPSC → common lymphoid progenitor + common myeloid progenitor → natural killer cell + T-lymphocyte + B-lymphocyte
B-Lymphocytes can differentiate further into plasma cells
haemopoietic stem cells features + sources
features
- capable of self renewal (more than any other adult tissue)
- given appropriate stimulo it can differentiate into a variety of specialised cells
- in pathological conditions eg myelofibrosis or thalassaemia can mobilize into circulating blood to colonise other tissues (extramedullary hematopoiesis)
- HPSC transplantation now mainstream haematological procedure
- if bone marrow is damaged in adult, HPSCs can move to spleen and RBCs can be produced
sources
- bone marrow aspiration
- leucopharesis (more on another card)
- umbilical cord stem cells
what is leucopharesis
technically not on learning objectives
- a way of collecting haemopoeitic stem cells (HPSCs)
- give patients GCSF to move stem cells out of bone marrow
- can therefore be collected by blood
- getting stem cells out of bone marrow via aspiration/biopsy is painful and expensive
reticuloendothelium system (RES)
spleen detail on another card
- part of immune system
- main organs are liver + spleen
- filter blood to identify pathogens and cells that are old/damaged → starts immune response
- made up of monocytes in the blood and a network of tissues that contain phagocytic cells
- spleen detail on another card
spleen
- part of reticuloendothelial system
- has red pulp (sinuses lined by endothelial macrophages + cords) and white pulp (similar structure to lymphoid follicles)
- blood enters through the splenic artery
- white cells and plasma preferentially pass through the white pulp
- red cells preferentially pass through the red pulp
FUNCTIONS
- sequestration and phagocytosis where old/abnormal cells removed by macrophages
- blood pooling where platelets and red blood cells can be rapidly mobilised during bleeding
- extramedullary haemopoiesis ie haemopoiesis going on in tissue outside the bone marrow. Pluripotent stem cells proliferate during haemotological stress or if marrow fails
- immunological function a significant number of B and T cells are present in the spleen
splenomegaly causes
why would it grow
- portal hypertension (eg in liver disease) where there is back pressure in portein vein and therefore in splenic vein, blood pools in spleen, enlarged
- over work
- expanding as infiltrated by cells eg cancer cells (eg leukaemia or metastases)
- expanding as infiltrated by other material (eg granulomas)
underlying causes
- MASSIVE: myeloid leukaemia, myelofibrosis, malaria, schistosomiasis
- MODERATE: lymphoma, leukaemias, myeloproliferative disorders, liver cirrhosis, infections eg glandular fever
- MILD: infectious hepatitis, endocarditis, infiltrative disorders such as sarcoidosis and autoimmune diseases
note: risk of rupture if spleen is enlarged an no longer protected by the rib cage - avoid contact sports and vigourous activity
splenomegaly causes
why would it grow
- portal hypertension (eg in liver disease) where there is back pressure in portein vein and therefore in splenic vein, blood pools in spleen, enlarged
- over work
- expanding as infiltrated by cells eg cancer cells (eg leukaemia or metastases)
- expanding as infiltrated by other material (eg granulomas)
underlying causes
- MASSIVE: myeloid leukaemia, myelofibrosis, malaria, schistosomiasis
- MODERATE: lymphoma, leukaemias, myeloproliferative disorders, liver cirrhosis, infections eg glandular fever
- MILD: infectious hepatitis, endocarditis, infiltrative disorders such as sarcoidosis and autoimmune diseases
note: risk of rupture if spleen is enlarged an no longer protected by the rib cage - avoid contact sports and vigourous activity
what is hypersplenism
- overactive spleen
- can cause splenomegaly
- low blood counts can occur due to pooling of blood in spleen
- when the spleen removes the blood cells to early and too quickly
- removes too many blood cells from the bloodstream
hyposplenism
features
- lack of functioning splenic tissue
- blood film reveals howell jolly bodies ★ which would normally be removed
causes
- splenectomy (have spleen removed), due to trauma or cancer
- sickle cell disease (affects membrane of RBC)
- gastrointestinal disease eg chron’s, colitis or coeliac
- autoimmune disorders eg lupus, rheumatoid arthritis or hashimoto’s (immune system also affects spleen, so cells leave spleen, and then spleen doesn’t function as it doesn’t have enough cells)
considerations
patients with this are at greater risk of sepsis from encapsulated bacteria (eg meningitis, Hib etc). As they are encapsulated, difficult for immune system to carry out response. Patients need to be given life long antibiotics.
★ DNA remnants which appear as tiny black dots in cells. Would normally be removed by fully functioning spleen
erythrocytes
red blood cells
- no nucleus and no mitochondria
- lifespan of 120 days
- bioconcave disk
- vital stats RBC (red blood cell count, how many?), Hb (haemoglobin, how effective?) and MCV (mean corpuscular volume, how large?)
functions
- deliver oxygen to tissues
- carry haemoglobin
- maintain haemoglobin in reduced (ferrous) state so it can bind to oxygen
- maintain osmotic equilibrium (maintains shape)
- generate energy (to keep cell membrane working)
haemoglobin
- tetramer of 2 pairs of globin chains
- each globin chain has its own haem group (includes iron)
- different globin chains will bind to make different forms of haemoglobin (has different properties, eg affinity)
- switch from fetal to adult Hb at 3-6 months of age
- exists as oxyhaemoglobin (relaxed binding structure) and deoxyhaemoglobin (tight binding structure)
red cell membrane structure and features
- bioconcave disk shape to maintain large surface area
- flexible so that it can squeeze through tiny capillaries
- changes in the components of the cell membrane (congenital or aquired) result in changes in RBC shape
- can cause cellls to become less deformable and more fragile
- spleen recognises cells as abnormal and removes them from circulation
- haemolytic anaemia can result
what is spherocytosis
technically not in LOs
come back to this
normal RBC is bioconcave, whereas these are sphere shaped
PROTEINS INVOLVED
- spectrin actin crosslinking and molecular scaffold protein that links the plasma membrane to actin cytoskeleton
- ankyrin links integral membrane proteins to the underlying spectrin-actin cytoskeleton
- band 3 facilitates chloride and bicarbonate exchange across membrane and also involved in physical linkage of membrane to cytoskeleton (binds with ankyrin and protein 4.2)
- protein 4.2 ATP-binding protein which may regulate the association of band 3 with ankyrin
degradation of haem
- when cells get old, senescent, they need to be removed
- senscent RBCs engulfed by macrophages in RES
- haem is released, and Fe2+ recycled
- unconjugated bilirubin released, and transported in blood bound to albumin (excess bilirubin causes jaundice)
- unconjugated bilirubin → bilirubin which is taken up by liver and conjugated with glucaronic acid (GA) → secreted in bile into duodenum
- in the duodenum, the GA is removed by bacteria, and bilirubin converted to urobilinogen which is subsequently oxidised to stercobilin
- some urobilinogen is absorbed into blood and transported to kidney
- urobilinogen is oxidised to urobilin and excreted in urine
note can distinguish between problems with liver/degradation of haem by looking at whether bilirubin is conjugated or unconjugated
this is because unconjugated bilirubin is named this before enters liver. Once it enters liver, called bilirubin
name: increase / reduction in the number of blood cells
reduction = cytopenia or pancytopenia
increase = panmyelosis
name: increase/reduction in the number of white blood cells
increase = leucocytosis
decrease = leucopenia
name: increase/reduction in the number of red blood cells
increase = polycythaemia or erythrocytosis
decrease = anaemia
