Haemopoiesis, The Spleen And Bone Marrow Flashcards
Haemopoiesis
Production of blood cells occurs in the bone marrow
Bone marrow extensive throughout the skeleton in infant
More limited distribution in adulthood - only found in the pelvis, Sherman, skull, ribs and vertebrae
Can do a bone marrow extraction in the pelvis to analyse the bone structure and body’s ability for haemopoiesis
5 major lineage pathways arise from haemopoietic stem cells in bone marrow
1) Platelets - via thrombopoiesis
2) RBC (erythrocytes) - via Erthropoiesis
3) Granulocytes (Basophils, Neurtrophils, Eosinophils) - via granulopoiesis
4) Monocytes (that mature to macrophages) via monocytopoiesis
5) T and B Lymphocytes - via lymphopoiesis
Differentiation determined by:
- Hormones
- Transcriptions factors
- Interactions with non-hamopoiteitc cell types e.g. endothelial cells
Important hormones - Erythropoietin secreted by kidney stimulates red blood cell production
Thrombopoietin produced by liver and kidney regulates production of platelets.
Haemopoietic stem cells (HPSCs)
Capable of self-renewal (more Sources of HPSC than any other adult tissue)
Given appropriate stimuli can differentiate into variety of specialised cells
In pathological conditions e.g. myelofibrosis or thalassaemia can mobilize into circulating blood to colonise other tissues (extramedullary hematopoiesis)
HPSC transplantation now mainstream haematological procedure
Sources of HPSCs - bone marrow aspiration (rarely done)
Granulocyte colony stimulating factor (GCSF) mobilised peripheral blood stem cells (collected by leucopharesis)
Umbilical cord stem cells Leicester has a cord bank
Reticuloendothelial system
Part of immune system and made up of monocytes in blood and a network of tissues which contain phagocytic cells
Role to remove dead or damaged cells and identify and destroy foreign antigens in blood and tissues
Main organs are spleen and liver
RES cells in spleen dispose of blood cells, in particular damaged or old red cells
The Spleen - Red pulp: sinuses lined by endothelial macrophages and cords
White pulp: similar structure to lymphoid follicles (important part of the immune system
Functions of the spleen in adults
Sequestration and phagocytosis - old/abnormal red cells removed by macrophages
Blood pooling - platelets and red cells can be rapidly mobilised during bleeding
Extramedullary haemopoiesis - pluripotential stem cells proliferate during haematological stress or if marrow fails (e.g. in myelofibrosis)
Immunological function - 25% of T cells and 15% of B cells are present in 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
Splenomegaly
Portal hypertension - Back pressure from the blood vessels where the bp has increasesed - portal hypertension usually found in liver disease
If the liver has been overworked - e.g. if one has consumed too much alcohol over years (red or white pulp)
Reverting to what it used to do- extramedullary haemopoiesis- if spleen is compromised liver will have to pick up the functions of the spleen (therefore leading to size increase)
Expanding as infiltrated by cells
Cancer cells of blood origin e.g. leukaemia
Other cancer metastases - from other cancers around the body
Expanding as infiltrated by other materials
Sarcoidosis (granulomas (the walling off of foreign substances e.g. infectious organisms)
Examination of the spleen
It is never normal for the spleen to be palpable below the costal margin
Start to palpate in Right Iliac Fossa (RIF) or may miss massive splenomegaly
Feel for spleen edge moving towards your hand on inspiration
Feel for the splenic notch
Measure in cm from costal margin in mid- clavicular line
Splenomegaly - clinical causes
Massive
Chronic myeloid leukaemia
Myelofibrosis
Malaria
Schistosomiasis
Moderate - diseases above can be moderate, plus -
Lymphoma
Leukaemias
Myeloproliferative disorders
Liver cirrhosis with portal hypertension
Infections such as Glandular Fever sports
Mild – diseases above can be mild, plus -
vigorous activity!
Infectious hepatitis
Endocarditis
Infiltrative disorders such as sarcoidosis
Autoimmune diseases such as AIHA, ITP, SLE
Hypersplenism - low blood counts can occur due to pooling of blood in enlarged spleen - risk of erupt urge if spleen enlarged and no longer protected by rib cage. - avoid contact sports
Hyposplenism
Lack of functioning splenic tissue
Causes:
-Splenectomy - may be required due to splenic rupture from trauma of because of cancer
-Sickle cell disease - in older children and adults due to multiple infarcts and fibrosis
-GI diseases - Crohns D, Ulcerative Colitis and Coeliacs disease
-Autoimmune disorders - Systemic Lupus, RA and Hashimoto’s diseases
Patients with hyposplenism are at risk of sepsis from encapsulated bacteria e,g, streptococcus pneumonia, meningococcus
Patients must be immunised and given life long antibiotic prophylaxis
When a Blood film is done from patients who have hyposplenism - Holly Jolly Bodies is seen - these are DNA remnants present in RBC - theses RBC would normally be removed by a fully functional spleen
Erythrocytes
Biconcave flexible disc ~8mm diameter Shape? No nucleus, No mitochondria, Lifespan ~120 days
Functions: - Deliver oxygen to tissues Carry haemoglobin Maintain haemoglobin in its reduced (ferrous) state Maintain osmotic equilibrium Generate energy
Haemoglobin - Tetramer of 2 pairs of globin chains each with its own haem group
Globin gene clusters on Ch 11 & 16
Different globin chains combine to form different haemoglobins with different properties
Switch from fetal to adult Hb at ~3-6 months of age
Hb exists in 2 configurations: Oxyhaemoglobin (relaxed binding structure) and deoxyhaemoglobin (tight binding structure)
RBC membrane structure
Changes in the components of the cell membrane (congenital or acquired) result in changes in RBC shape
-Proteins involved in hereditary spherocytosis -
Spectrin: actin crosslinking and molecular scaffold protein that links the plasma membrane to the 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
Changes to the plasma membrane cause cells to become less deformable & more fragile.
Spleen recognises cells as
Degradation of haem
When RBC are damaged or old, macrophages in liver identify these and are scooped up with components being broken down
Globin chains are recycled and HB molecule has iron taken out and iron is recycled
HB then circulates as bilirubin as blood and taken to the liver when bilirubin circulates in blood its known as unconjugated - in the liver its conjugated with glucaronic acid
Excess unconjugated bilirubin in the blood can cause jaundice (e.g. from haemolytic anaemia)
This is then secreted into the bile into the duodenum, where glucoronic acid is removed and bilirubin is converted to stercobilin - which makes poo brown - some can be absorbed in gut and taken to kidney, and oxidised to urobilin and is secreted in urine making urine yellow
Neutrophils
First-responder phagocyte
Most common white cell
Essential part of innate immune system
Circulate in bloodstream & invade tissues – live for 1-4 days
Maturation controlled by hormone (granulocytic - cytokines secreting factor) G-CSF, a glycoprotein growth factor & cytokine which:
Increases production of neutrophils
Speeds up release of mature cells from BM
Enhances chemotaxis
Enhances phagocytosis and killing of pathogens
Recombinant G-CSF is routinely administered in cases when more neutrophils are needed e.g. a patient with severe neutropenia and sepsis after chemotherapy
Neutrophilia
An increase in the number of circulating neutrophils
Wide range of causes - Infection - Tissue damage - Smoking - Drugs (e.g. steroids) - Myeloproliferative diseases - Acute inflammation - Cancer - Cytokines (G-CSF) - Metabolic disorders - Endocrine disorders - Acute Haemorrhage
Only those cells in circulating pool are actually measured in a blood count - Haemorrahge brings more cells out from marginated pool
Neutropenia
Neutrophil count <1.5x10 9/L (severe if <0.5x10 9>)
Consequence of neutropenia - severe life threading bacterial infection
Severe life threading fungal infection
mucosal ulceration e.g. painful mouth ulcers
Neutropenia sepsis is a medical emergency
Intravenous antibiotics must be used immediately
Causes go between reduced production or increased removal
Reduced production - viral infection, drugs, B12/folate deficiency, aplastic anaemia
Increased removal - immune destruction, sepsis (causes rapid migration into tissues and spleen cant make enough to keep numbers high enough), splenic pooling due to splenomegaly
