Physiology Flashcards
What are the 3 types of blood cells
Red blood cells
White blood cells
Platelets
Haematopoiesis
The production of blood cells
Haematopoiesis in the embryo
Yolk sac , then liver , then marrow
When do blood cells start to be produced in the spleen in an embryo
3rd - 7th month
Where are blood cells produced at birth
Mostly bone marrow
Where are blood cells produced during childhood
Bone marrow
Where are blood cells produced in an adult
Restricted to skull, ribs, sternum, pelvis and proximal ends of the femur
State the 3 types of white blood cells
Granulocytes
Monocytes
Lymphocytes
Name the 3 types of granulocytes
Neutrophils
Eosinophils
Basophils
What do neutrophils look like
Segmented nucleus , stains neutral
4 ways to assess haemopoeisis
- peripheral blood (blood count and film)
- bone marrow
- immunophenotyping
- other signs e.g. splenomegaly, hepatomegaly
Where is bone marrow usually taken from
Posterior iliac crests
Which 2 key organelles do red blood cells not have
Nucleus and mitochondria
What maintains water balance in red blood cells
Sodium-potassium pump
Structure of haemoglobin in most adults
2 alpha chains and 2 beta chains
Structure of foetal haemoglobin
2 alpha chains and 2 gamma chains
Structure of haemoglobin in HbA2
2 alpha chains 2 delta chains
How many oxygen molecules can bind to one haemoglobin
4
State 3 functions of haemoglobin
- delivers oxygen to tissues
- acts as a buffer for H+
- CO2 transport
Erythropoiesis
Red cell production
Where does erythropoesis occur
Bone marrow
What regulates erythropoiesis
Erythropoietin
Where is erythropoietin found
In the kidneys
On which chromosome are alpha like genes found
16
How many alpha genes do we have per chromosome
2
On which chromosome are beta like genes found
11
Where does RBC destruction usually occur
Spleen and liver
What is the haem group broke down to
Iron and bilirubin
What is metHb
Hb with Fe3+ instead of Fe2+
Embden-Meyerhof pathway
Red blood cells are able to generate ATP and NADH through the glycolysis pathway
What can cause an oxygen dissociation curve to the right (3)
2,3-DPG
Low pH
Increased temperature
What is the main role of iron in the body
Crucial for reversible oxygen binding to haemoglobin
Name 3 biological components in which iron is present
- haemoglobin
- myoglobin
- enzymes
What is a potential risk associated with iron due to its chemical reactivity
Can lead to oxidative stress and the production of free radicals
Where does iron absorption occur
Duodenum
What enhances iron absorption (3)
- haem vs non-haem iron
- ascorbic acid
- alcohol
What inhibits iron absorption (3)
- calcium
- tannins (e.g. tea)
- phylates
Where are phylates found in the diet
Cereals, bran, nuts, seeds
What is the main regulator of iron uptake
Hepcidin
When and where is hepcidin produced
In the liver in response to increase iron load and inflammation
Role of ferroportin
Facilitates iron export from the duodenal enterocyte
What transports iron around the body
Trasferrin
Role of hepcidin
Binds to ferroportin and causes its degradation
Where are lots of transferrin receptors found
Erythrocytes marrow
What does low ferritin suggest
Iron deficiency
How do we assess functional iron
Haemoglobin concentration
How do we assess transport iron
% saturation of transferrin with iron
How do we assess storage iron
Serum ferritin
Haemostasis
The arrest of bleeding and the maintenance of vascular patency
State the 4 components of a normal haemostatic system
- formation of a platelet plug
- formation of fibrin clot
- fibrinolysis
- anticoagulant defences
Primary haemostasis
Formation of a platelet plug
Secondary haemostasis
Formation of a fibrin clot
How and where are platelets formed
In the marrow by budding from Megakaryocytes
Formation of a platelet plug (4)
- endothelial wall damage
- exposes collagen and releases von willebrand factor
- secretion of chemicals from the platelets
- aggregation at the site of injury
State the 3 causes of failure of the platelet plug formation
- vascular
- platelets
- Von Willebrand factor deficiency
Vascular causes of failure of the platelet plug formation (3)
- Marfans
- vasculitis
- vit C deficiency
Consequences of failure of platelet plug formation (4)
- easy bruising
- mucosal bleeding
- intercranial haemorrhage
- retinal haemorrhage
Screening test for primary haemostasis
Platelet count
Causes of failure of fibrin clot formation (4)
- single clotting factor deficiency
- liver failure
- vit K deficiency
- increased fibrinolysis
Test which identifies failure in the extrinsic pathway
prothrombin time
Test which identifies failure in the intrinsic pathway
Activated partial thromboplastin time
Lifespan of a RBC
120 days
Lifespan of a neutrophil
7-8 hours
Lifespan of platelets
7-10 days
What are blasts
Nucleated precursor cells
Megakaryocytes
Platelet precursor
Myelocytes
Nucleated precursor between neutrophils and myeloblasts
Reticulocyte
Immature red blood cells
What is proliferation
Increase in numbers
Where do haemopoietic stem cells originate embryonically
Mesoderm
How are mature blood cells released from the bone marrow
Pass through fenestrations in endothelial cells of the sinusoids
What is the release of RBCs from the marrow associated with
Sinusoidal dilation and increased blood flow
Difference between red and yellow marrow
Red is active, yellow is fatty and inactive
What regulates neutrophil precursor maturation
G-CSF
What is the role of thrombopoietin
Regulates the growth and development of Megakaryocytes from their precursors
What are lymphatic channels
Blind ended vessels that permit passive unidirectional flow of lymphatic fluid
Role of the lymphatic system
Prevents oedema by returning fluid from extracellular connective tissues to the circulation
What are the 3 important regions of a lymph node
Cortex
Paracortex
Medulla
Cortex of a lymph node
Nodules of B lymphocytes arranged in follicles
Paracortex of a lymph node
Mainly T lymphocytes
Forms interfollicular tissue which surrounds follicles and extends out and merges with medulla
Medulla of a lymph node
Contains cords and sinuses draining into the hilum
What happens in the dark zone of a lymphoid follicle
Clonal expansion and somatic hypermutation
What happens in somatic hypermutation
The DNA of B cells undergoes random mutations leading to changes in the antibody genes
What happens in the light zone of a lymphoid follicle
B cell selection and affinity maturation
How do B cells move from the dark zone to light zone
Increased antigen affinity
What happens to positively selected B cells in the light zone
Re enter dark zone and keep proliferating
Differentiate into plasma cells
Differentiate into memory B cells
Role of follicular dendritic cells (3)
provide architectural support to Germinal centre
Facilitates debris removal through secreting bridging factor
Role in antigen capture for memory B cells
What is a centroblast
Proliferating B cell in the dark zone
What is a Centrocyte
Differentiated centroblast
B cell in the light zone
Flow of lymphatics (5)
Afferent channels drain lymph through the capsule into the subscapular sinus
Percolates through the node
Enters medullary cords and sinuses
Sinuses merge at hilum and form efferent lymphatics
Lymph rejoins extranodal circulation
Troiseries sign
Manifestation of metastasis from an abdominal malignancy
Sentinel lymph node
The first lymph node to which cancer cells are likely to spread
2 characteristics of malignant haemopoiesis
Increased numbers of abnormal and dysfunctional cells
Loss of normal activity
What are the causes of abnormal haemopoiesis in malignancy
Increased proliferation in the absence of a stimulus
Lack of differentiation
Lack of maturation
Molecular pathogenesis in acute leukaemia
Proliferation of abnormal progenitors with a block in differentiation and maturation
Molecular pathogenesis in chronic myeloproliferative disorders
Proliferation of abnormal progenitors but no differentiation or maturation block
What are clones
Population of cells derived from a single parent cell
What are the 3 main ways we can class haematological malignancies
Lineage
Developmental stage
Anatomical site involved
2 different types of lineage in haematological malignancy
Myeloid or lymphoid
Naming haematological malignancies based on developmental stage
Blastic is primitive
Cytic is more mature
What is the exception to naming haematological malignancies based in anatomical site involved
Chronic lymphocytic leukaemia
Can involve both blood and lymph nodes
Features of histological aggression in haematological malignancies
Large cells with high nuclear-cytoplasmic ratio
Prominent nucleoli
Rapid proliferation
Features of clinical aggression in haematological malignancies
Rapid progression of symptoms
What are immunoglobulins
Antibodies produced by b cells and plasma cells
What are immunoglobulins made from
Proteins made from 2 heavy chains and 2 light chains
What determines the class of antibody produced
The heavy chain type
How can immunoglobulins be used
Can be expressed on B cell surfaces
Released into the blood stream as antibodies by plasma cells
Role of B cells
Antibody production
Act as antigen presenting cells
Role of plasma cells
Produce large quantities of antibody
Polyclonal increase in immunoglobulins
Ig produced by many different plasma cell clones
What does polyclonal increase in immunoglobulins indicate
A reactive cause
Monoclonal increase in immunoglobulins
All derived from clonal expansion of a single B cell
What are the 2 ways we can detect immunoglobulins
Serum electrophoresis
Serum immunofixation
Bence jones protein
Immunoglobulins light chains present in myeloma
How do we detect Bence jones protein
Urine electrophoresis and immunofixation
