Haemopoiesis, bone marrow and spleen Flashcards
(39 cards)
Where does haemopoiesis occur?
Bone marrow of the axial skeleton and skull in adults
(Extensive throughout the skeleton in infants)
What determines the differentiation of haemopoietic stem cells?
Hormones
Transcription factors
Interactions with non-haemopoietic cell types (e.g. endothelial cells)
Which hormone stimulates RBC production and what is it secreted by?
Erythropoietin - secreted by kidney
Which hormone regulates platelet production and what is it secreted by?
Thrombopoietin - secreted by kidney and liver
In pathological conditions like myelofibrosis or thalassaemia, where does haemopoiesis occur?
Haemopoietic stem cells can migrate into circulating blood and colonise in other tissues. EXTRAMEDULLARY HAEMOPOIESIS occurs in tissues where haemopoiesis previously occurred in early life (e.g. spleen or liver)
How are dead or damaged blood cells removed?
The reticuloendothelial/ lymphatic system is part of the immune system and is made of monocytes and tissues with phagocytic cells. Main organs involved are spleen and the liver.
What are the two major parts of the spleen and what are their functions?
- Red pulp: sinuses lined by endothelial macrophages - identify abnormal cells or foreign antigens and move it to white pulp
- White pulp - similar to lymphoid follicles and contains lymphocytes that can trigger an immune response
What are the functions of the spleen? (4)
- Identifying and removing old/abnormal red cells
- Mobilising blood pooling platelets and RBCs during bleeding
- Extramedullary haemopoiesis - pluripotent stem cells proliferate during haematological stress or if bone marrow fails
- Immunological function - 25% of T-cells and 15% of B-cells reside in the spleen
How does blood enter, pass through and leave the spleen?
Blood enters via the splenic artery
- White cells and plasma preferentially pass through the white pulp
- Red cells preferentially pass through the red pulp
Blood leaves via the splenic vein which joins the portal vein
Why can splenomegaly occur? (5)
- Portal hypertension - tension in portal vein builds back pressure in splenic vein so blood cannot leave the spleen at a normal rate
- Overwork of red or white (high abnormal cells leads to higher removal rate)
- Extramedullary haemopoiesis
- Expansion caused by infiltrated cells (cancer cells of blood origin e.g. leukaemia or cancer metastases)
- Expanding as infiltrated by other material (granulomas)
How would you examine the spleen?
Spleen should not be found below the costal margin
Start to palpate in RIGHT ILLIAC FOSSA and move up to the LEFT HYPOCHONDRIAC region - and feel the splenic notch
What are patients with splenomegaly at risk of?
Splenic rupture - enlarged spleen is not protected by the rib cage
patients must avoid contact sports and vigorous activity
What are the impacts of splenomegaly/ hypersplenism on blood counts?
Low blood counts - low white cell, red cell and platelet count. Occurs due to pooling of blood in the spleen
What is hyposplenism and what are its causes? (4)
Lack of functioning splenic tissue caused by:
1. Splenectomy
2. Sickle cell disease: causes infarcts in the spleen and fibrosis
3. GI diseases (Coeliac and Crohn’s disease; ulcerative disease)
4. Autoimmune disease: systemic lupus, RA, Hashimoto’s disease
What are patients with hyposplenism are risk of?
Sepsis/infections from encapsulated bacteria
E.g. Neisseria meningitis, Haemophilus influenzae, Sterptococcus pneumonia (NHS)
Patients are immunised and given lifelong antibiotic prophylaxis
What can be observed in blood films of patients with hyposplenism?
Howell Jolly inclusion bodies - red cells contain inclusion bodies (appear as dark spots inside cells) which are usually removed by the spleen. These inclusion bodies are remnants of the nucleus (DNA remnants)
What are the functions of erythrocytes?
Carry O2 to tissues
- carry Hb
- maintain Hb in its reduced/ferrous state (Fe2+)
- maintain osmotic equilibrium
- generate energy
What are structural features of Hb?
- It is a tetramer of 2 pairs of globin chain and each chain has its own haem group
- Globin gene clusters in C-some 11 and 16
- Different globin chains combine to form different Hb with different properties
- Switch from fetal to adult Hb at 3-6 months
- Hb exists in oxyHb or deoxyHb forms
Which proteins are involved in maintaining the RBC membrane structure?
Spectrin: actin crosslinking and molecular scaffold protein that link PLASMA membrane to the ACTIN CYTOSKELETON (alpha and beta spectrin)
Ankyrin: Links integral membrane proteins to the underlying spectrin-ankyrin cytoskeleton
Band 3: allows chloride and bicarbonate exchange across membrane and links membrane to the cytoskeleton by binding to ankyrin and protein 4.2
Protein 4.2: ATP-binding protein that regulates the binding of band 3 to ankyrin
Describe the degradation of haem
- Senescent red blood cells are engulfed by macrophages in RES
- Once broken down, Fe2+ is released into circulation to be recycled
- Haem is then broken down to unconjugated bilirubin
- Unconjugated bilirubin is transported to liver to be conjugated (excess can cause jaundice)
- The liver conjugates bilirubin with GLUCORONIC ACID to produce bilirubin diglucoronide
How does the liver conjugate bilirubin? What is conjugated bilirubin called?
With glucoronic acid
Bilirubin diglucoronide
How is conjugated bilirubin processed and disposed?
- Bilirubin glucoronide is secreted in bile into the duodenum
- Glucoronic acid is removed by bacteria in the gut and bilirubin is converted to urobilinogen which is oxidised to stercobilin
- Stercobilin is disposed in faeces
- Some urobilinogen is absorbed into blood, transported to kidney and is oxidised to urobilin -> excreted in urine
What does ‘cytopenia’ mean?
reduction in the number of cells
What does ‘cytosis’ or ‘philia’ mean?
increase in the number of cells
