Haemopoiesis , The Spleen And Bone Marrow Flashcards
Define haemopoiesis
Production of blood cells
In an infant , where does haemopoiesis occur mainly ?
Extensive throughout the skeleton as an infant
In an adult , where does haemopoiesis occur ?
It becomes more limited and only occurs :
1) bone marrow of pelvis
2) bone marrow of the sternum
3) bone marrow of the ribs
4) bone marrow of the skull
5) bone marrow of the vertebrae
What is a thine biopsy ?
Method of looking at bone marrow using a needle which extracts liquid bone marrow from specific areas in the body
What do thrombocytes , granulocytes , lymphocytes and monocytes all arise from ?
Multipotent hematopoietic cell
What does the hematopoietic stem cell differentiate into? What two cells
1) common lymphoid progenitor
2) common myeloid progenitor
What is differentiation determined by ?
1) hormones
2) transcription factors
3) interactions with non-haemopoietic cell types eg endothelial cells
What are the two important hormones called that help regulate differentiation of the hematopoietic stem cell ?
1) thrombopoietin
2) erythropoietin
Where is ertpythropoiten secreted from and what is its role ?
Secreted from the kidneys
- it stimulates red blood cell production during periods of stress for example when oxygen levels in the blood is low this is called ‘ hypoxia ‘
Where is thrombipoietin secreted from and what is its function?
Secreted from the liver and the kidneys
- regulates the production of platelets
What are a few characteristics of the hematopoietic stem cell ?
1) capable of self renewal ( they can produce themselves again)
2) they can differentiate into a variety of specialised cells
3)
What are the two sources of hematopoietic stem cells ?
1) bone marrow
2) umbilical cord stem cells
What is the recticuloendothelial system ?( RES)
- part of the immune system and made up of monocytes in blood.
- main organs are the liver and spleen
- role is to remove dead or damaged cells and identify and destroy foreign antigens in blood and tissue
What are monocytes called when they enter the tissue ?
Macrophages
Where are kupffer . Cells found ?
They are found in liver tissue
- they are macrophages
Where are tissue histiocytic found ?
They are found in connective tissue
- they are a type of macrophage
- part of the RES system
Where are microglial found ?
In the central nervous system
- they are a type of macrophage
Where are peritoneal macrophages found ?
- peritoneal cavity
- they are a type of macrophage
Where are red pulp macrophages found ?
In the spleen
Where are langerhans cells found ?
In the skin( epidermis) and mucosa
What are the 4 functions of the spleen ?
1) sequenstration and phagocytosis - the red pulp macrophages remove 120 day old red blood cel,s
2) Blood pooling platelets and red blood cells can be rapidly mobilised during periods of stress eg ( when you are bleeding )
3) they have extramedullary haemopoiesis:pluripotent stem cells proliferate during haematological stress or if marrow fails.
4) immunological function: 25% of T cells and 15% of B cells are present in the white pulp of the spleen
How does blood enter the spleen ?
Via the splenic artery : white cells and plasma preferably pass through the white pulp
- red cells preferentially pass through the red pulp
What is splenomegaly?
Abnormal growth of the spleen
What causes splenomegaly?
1) overwork of the red or white pulp. For example when there is a disorder in red blood cells or bone marrow - the red pulp may work extra hard.
2) Portal hypertension in liver disease ( there is an increase in blood pressure within the portal venous system of the liver )
3) Extramedullary haemopoiesis
4) expanding due to cancer cells ( leukaemia , other cancer metastasis )
5) expanding as infiltrated by other material such as sarcoidosis ( abnormal collecting of inflammatory cells which leads to lumps known as granulomas )
Is it normal for the spleen to be palpable below the costal margin ?
No
What are ttwo major consequences of splenomegaly?
1) more ofyour blood volume would sit the spleen which would decrease blood count.
2) Major risk of rupture if spleen is enlarged and no longer protected by ribcage so they are often advised to not engage in extreme sports
What diseases can cause mild splenomegaly?
- infectious hepatis
- endocarditis
- sarcoidosis
- autoimmune diseases such as AIHA , ITP, SLE
What diseases can cause moderprate splenomegaly?
- lymphoma
- leukaemia
- liver cirrhosis with portal hypertension
- infections such as glandular fever
- myeloproliferative disorders
What diseases can lead to massive splenomegaly?
1) malaria
2( chronic myeloid leukaemia
3) schstiosomiasis
What is hyposplenism ?
Reduced functioning of splenic tissue
What are causes of hyposplenism ?
1) splenectomy
2) sickle cell disease
3) GI diseases ( Crohn’s disease , ulcerative colitis , coeliac disease)
4) autoimmune diseases such as systemic lupus , rheumatoid arthritis , hashitomos disease
What are patients with hyposplenism at risk of ?
SEPSIS from encapsulated bacteria such as streptococcus pneumonia , meningococcus and haemophilus influenza
Someone with hyposplenism, what would be seen on a blood film ?
HOWELL JOLLY BODIES
- which are DNA remnants. These are normally removed by a fully functioning spleen,
At what age does fetal HB change to adult HB ?
3-6 months from birth
What is the reference range of RBC ?
4.4 -5.9 x10^21 / l
What is the reference range for HB?
13.5-16.7 g/dl
What is the reference range for MCV?
80-100 fl
What is the diameter size of the red blood cell ?
8 micro metres
Why is the red blood cell cell membranes so important ?
Because changes in the cell membrane can result in changes in the red blood cell shape
- this can lead to red blood cells becoming much LESS flexible and less deformable , which leads to an increase in fragility
- haemolytic anaemia can result.
Outline th eprocess by which haemoglobin is broken down ?
1) red blood cells are engulfed by macrophages in the RES.
2) globin is recycled so is the Fe2+. However Haem is converted into bilirubin,
3) bilirubin remains Unconjugated when it is transported in blood bound to albumin,
4) bilirubin is taken up by the liver and becomes conjugated with glucuronic acid. Secreted in bile into duodenum.
5) glucuronic acid removed. Bilirubin is converted to urobilinogen which is then oxidised Into stercobilin.
6) excreted as faeces ( stercobilin gives poo the brown colour.
7) some urobilinogen is absorbed into the blood and transported into kidney. Oxidised into urobilin. And excreted in urine. Urobilin gives urine colour colour.
Define cytopenia
Reduction in number of blood cells
Define cytosis/Philia
Increase in the number of blood cells
What is the most common white cell ?
Neutrophils
How long do neutrophils live for ?
1-4 days
Maturation of neutrophils is controlled by what hormone ?
G-CSF ( glycoprotein growth factor & cytokine)
What does GCSF responsible for ?
Increases production of neutrophils
- speeds release of mature cells from bone marrow
- enhances chemotaxis
- enhances phagocytosis and killing of pathogens
When is GCSF routinely given to patients ?
- sepsis after chemotherapy
- a patient with severe neutopenia
Define neutrophilia
An increase in the absolute number of circulating neutrophils
What are a few causes of neutrophila ?
1) infection ()
2) tissue damage
3) smoking
4) GCSF ()
5) myeloproliferative diseases (*)
Define neutropenia
Decrease in the absolute number of circulating neutrophils
What are a few consequences of neutropenia?
1) severe life threading bacteria infection ( eg neutropenic sepsis)
2) severe life threatening fungal infections
3) mucosal ulceration ( painful mouth ulcers )
What must be given to someone immediately if they have neutropenic sepsis ?
Intravenous antibiotics
What are the two subcategories for the causes of neutropenia?
1) reduced production
2) increased removal or use
What causes reduced production of neutrophils
1) radiation which kills mature cells
2) viral infections
3) congenital
4) drugs ( eg chemotherapy , Antibiotics)
5) B12/folate deficiency
What causes increased Rome all or use of neutrophils ?
1) immune destruction
2) sepsis
3) splenic pooling ( sequenstration of neutrophils in the spleen means there is less available for general circulation)
What are the largest cells in the blood ?
Monocytes
How long do monocytes circulate for in the blood before migrating into different tissues ?
1-3 days
What is the function of monocytes ?
1) phagocytosis microorganisms
2) antigen presenting role to lymphocytes
3) important defence against chronic bacterial infections such as Tb and chronic fungal infections
What are the causes of monocytosis ?
1) carcinoma
2) bacterial infections eg tb
3( infkallatory conditions such as rheumatoid arthritis
4) myeloproliferative disorders and leukaemia
How long do eosinophils circulate in the blood before migrating into different tissues z.
3-8 hours
What is then.ife span of eosinophils ?
8-12 days
What is the function of eosinophils ?
- reposmible for immune response against multicellular parasites such as helminths
What are common causes of eosinophils?
1) allergic diseases such as asthma and eczema
2; drug hypersentivity eg penicillin
3) skin diseases
4) parasitic infections eg round worms , tape worms , helminths
What are rare causes of eosinophilia.
1) Hodgkin lymphoma
2) myeloproliferative conditions
What is the least common granulocytes?
Basophils
What is the function of basophils ?
- large dense granules containing histamine , heparin , hyaluronic acid and serotonin
What causes basophilia?
1) rheumatoid arthritis
2) immediate hypersentivity reactions
3( ulcerative Collitis
4) myeloproliferative
What are the three types of lymphocytes ?
1) B cells
2) T cells
3) natural killer cells
- they all originate in the bone marrow
What causes lymphocytosis?
1) viral infections
2) bacterial infections especially whooping cough ,
3) stress related ( MI/cardiac arrest)
4) post splenectomy
5) smoking
6) chronic lymphocytic leukaemia
7) lymphoma
