S3 L1 - Haemopoiesis, the Spleen and Bone Marrow Flashcards
- *Haemopoiesis:**
- What is this?
- Where does it occur in adults?
- Where does it occur in infants?
- What way can it be investigated?
- *5 major lineage pathways arise from haemopoietic stem cells in bone marrow**
- Draw map of this
- What are important hormones involved
- What is this?
Production of blood cells occurs in the bone marrow
- Where does it occur in adults?
Axial skeleton - Pevlis, sternum, skulls, ribs, vertebrae
- Where does it occur in infants?
Bone marrow extensive throughout the skeleton in infant
- What way can it be investigated?
Trephine biopsy
5 major lineage pathways arise from haemopoietic stem cells in bone marrow
- Draw map of this
(pic)
- What are important hormones involved
—- Erythropoietin - Secreted by kidney stimulates red blood cell production
—- Thrombopoietin - Produced by liver and kidney, regulates production of platelets
- *Haemopoietic stem cells (HPSCs)**
- Properties of HPSCs
- Sources of HPSC
Properties:
• Capable of self-renewal (more 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 HPSC:
• Bone marrow aspiration (rarely done)
• GCSF mobilised peripheral blood stem cells (collected by leucopharesis)
• Umbilical cord stem cells Leicester has “cord bank” (1 of 4 in UK)
- *Reticuloendothelial system (RES):**
- What is the RES
- Role of the RES
- Main organs in RES
- *Spleen:**
- 2 parts
- *Functions of the spleen in adults:
- ** 4 main roles
- How blood enters the spleen
- What is the RES
Part of the immune system and made up of monocytes in the blood and a network of tissues which contain phagocytic cells
- Role of the RES
Remove dead or damaged cells and identify and destroy foreign antigens in blood and tissues
- Main organs in RES
Spleen and liver
Spleen:
2 parts…
- Red pulp: Sinuses linned by endothelial macrophages and cords. RBC go through through and are cleared
- White pulp: Similar structure to lymphoid follices. Lymphocytes go through it, to get an immune response
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 spleen
How blood enters 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:**
- Why would the spleen grow?
Examination of spleen
- Back pressure- portal hypertension in liver disease
- Over work (red or white pulp)
- Reverting to what it used to doextramedullary haemopoiesis
- Expanding as infiltrated by cells: e.g. infiltrated by cancer cells, Cancer cells of blood origin e.g. leukaemia, other cancer metastases
- Expanding as infiltrated by other material, e.g. Sarcoidosis (granulomas)
Examination of spleen:
pic
- *Splenomegaly - Clinical**
- Some causes
- How can hypersplenism affect blood counts
- What is the risk of an enlarged spleen
- Some causes:
Massive: • Chronic myeloid leukaemia • Myelofibrosis • Malaria • Schistosomiasis
Moderate – as above, plus: • Lymphoma • Leukaemias • Myeloproliferative disorders • Liver cirrhosis with portal hypertension • Infections such as Glandular Fever
Mild – as above, plus: • Infectious hepatitis • Endocarditis • Infiltrative disorders such as sarcoidosis • Autoimmune diseases such as AIHA, ITP, SLE
- How can hypersplenism affect blood counts
Low blood counts can occur due to pooling of blood in enlarged spleen
- What is the risk of an enlarged spleen
Risk of rupture if spleen enlarge and no longer protected by rib cage - avoid contact sports and vigorous activity
- *Hyposplenism:**
- Causes
- Blood film - what are you likely to see?
- Clinical issues with hyposplenism
Hyposplenism:
- Causes
• Splenectomy: May be required due to splenic rupture from trauma or because of cancer
• Sickle cell disease: In older children and adults due to multiple infarcts & fibrosis
• Gastrointestinal diseases: - Coeliac disease - Crohn’s disease - Ulcerative colitis
• Autoimmune disorders: - Systemic lupus - Rheumatoid arthritis - Hashimoto’s disease
- Blood film - what are you likely to see?
Blood film reveals Howell Jolly bodies (DNA remnants)
- Clinical issues with hyposplenism
Key clinical fact Patients with hyposplenism are at risk of sepsis from encapsulated bacteria e.g. • Streptococcus pneumonia • Haemophilus influenzae • Meningococcus
Patients must be immunised and given life long antibiotic prophylaxis
- *Erythrocytes:**
- Vital statistics
- Functions
- Haemoglobin – globin chains, what types of haemoglobin are there…
Red cell membrane structure
- Vital statistics:
RBC (Red Blood Cell Count) How Many? 4.4 - 5.9 x 1012/l
Hb (Haemoglobin) How effective? 13.5 - 16.7 g/dl
MCV (Mean Corpuscular Volume) How large? 80 - 100fl
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 – globin chains, what types of haemoglobin are there…
• 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
Red cell membrane structure:
pic
- Haemolytic anaemia
- Hereditary spherocytosis
- *Degradation of haem**
- How are red blood cells recycled
Terminology about blood cells:
- What is the word for a reduction in the number of blood cells
- What is the word for an increase in the number of blood cells
- Type of cell, what is the word for increase and decrease (see pic)
- What is the word for a reduction in the number of blood cells: Cytopenia
- What is the word for an increase in the number of blood cells:
…cytosis and …philia - Type of cell, what is the word for increase and decrease (see pic)
(pic)
- *Neutrophils:**
- Role
- Function of G-CSF
- What is recombinant G-CSF and when is it commonly used?
Neutrophils:
- Role:
First-responder phagocyte • Most common white cell • Essential part of innate immune system • Circulate in bloodstream & invade tissues – live for 1-4 days
- Function of G-CSF:
• Increases production of neutrophils • Speeds up release of mature cells from BM • Enhances chemotaxis • Enhances phagocytosis and killing of pathogens
- What is recombinant G-CSF and when is it commonly used?
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**
- What is this
- Causes
- *Neutropenia**
- What is this
- Consequences of neutropenia
- Causes of neutropenia
- Key clinical fact – of neutropenic sepsis
What does haemorrhage do to the neutrophil count?
Increase with bacterial infections!
Neutrophilia:
- An increase in the absolute 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
- Acute haemorrhage: Only those in circulating pool are actually measured in a blood count. Haemorrhage brings more cells out from marginated pool.
Neutropenia:
(pic)
- *Monocytes**
- Role
- Causes of monocytosis
- Role:
• Normally largest cells in blood
• Circulate for ~1-3 days before migrating into tissues where they differentiate into macrophages or dendritic cells
• Phagocytose microorganism and breakdown/remove cellular debris
• Antigen presenting role to lymphocytes
• Important in defence against chronic bacterial infections (e.g. tuberculosis and chronic fungal infections
- Causes of monocytosis:
• Bacterial infection e.g. tuberculosis
• Inflammatory conditions e.g. rheumatoid arthritis, Crohn’s Ulcerative colitis
• Carcinoma
• Myeloproliferative disorders and Leukaemias
- *Eosinophils**
- Role
- When are they seen in increase quantities?
- Causes of eosinophilia
- Parasitic infections
- Allergies
- *Basophils:
- **When do you see these a lot?
- What do the granules contain?
- What do they look like on a film?
Basophilia:
Causes
- When do you see lots of basophils?
Active in allergic reactions and inflammatory conditions
- What do the granules contain?
Granules contain: histamine, heparin, hyaloronic acid, serotonin
- What do they look like on a film?
Granules stain deep blue to purple
Causes of Basophilia
Reactive:
• Immediate hypersensitivity reactions • Ulcerative Collitis • Rheumatoid Arthritis
Myeloproliferative:
• CML • MPN: ET/PRV/MF • Systemic mastocytosis
- *Lymphocytes**
- 3 types
- Lymphocytosis causes
- Viral infection (increased in numbers)
