Physiology Flashcards
Name the different types of blood cells
- white
- red
- platelets
What is haematopoiesis
- production of blood from bone marrow
- derived from pluripotent stem cells
What is red cells dervived from?
- pluripotent stem cells
Where does haematopoiesis occur in the embryo? and then when at birth?
- embryo = yolk sac, then liver, then bone marrow
- adult = bone marrow, liver, spleen
Which bone marrow is responsible for the production of red blood cells?
- the axial skeleton
Explain the formation of blood cells from the stem cells?
- proliferation
- differentiaion
- haematopoietic trees
What are the 2 main routes in the haematopoietic tree and their final product
- cmp (myeloid) -> granulocytes, erythrocytes, platelets, macrophages
- CLP (lymphoid) -> B cells, T cells and NK cells
What state do most stem cells lie in?
- quiescent state
Term given to red cell production, different from blood cell production
- erythropoiesis
What is the primary cell called of erythropoiesis?
- pronormoblast
- early normoblast
- intermediate normoblast
- late normoblast
- reticulocyte
- erythrocyte
What is the difference between a reticulocyte and a erythrocyte?
- a reticulocyte is more immature and contains a nucleus and is found in bone marrow
- erythrocyte has no nucleus and has entered blood streem
Explain platelet formation
- nucleus replicated but no cell division
- forms a megakaryocyte
- budding off -> platelets released
3 main granulocytes?
- eosinophils
- basophills
- neutrophils
Describe neutrophils
- most numerous white cell
- fine granules
- lobbed nucleus
- short lived
What may cause an increase in neutrophils?
- infection
- trauma
- infarction
Describe the appearance of eosinophils
- bi-lobbed
- bright red granules
- involved in hypersensitivity
Describe appearance of basophils?
- large purple granules
- basic staining
- release histamine
Monocytes vs macrophages
- monocytes = in the blood stream
- macrophages = in the tissue
Describe the appearance of lymphocytes
- big nucleus
3 ways of sampling blood in haematology?
- immunophenotyping
- bio-assay
- bone marrow samples
Explain immunophenotyping
- looking at surface proteins of cells
- much quicker method
Structure of RBC
- 2 alpha
- 2 beta
- 4 porphyrin rings with Fe2+
- biconcave
- no nucleus
- no mitochondria
Why are RBC limited to 120days?
- they have no nucleus or mitochondria
- unable to repair proteins
What is present on the cell membrane of a RBC
- Sodium potassium ATP pump
What is the disadvantage of Fe3+
- unable for O2 to bind
- must be in Fe2+ form
NADH generated in glycolysis helps protect Fe2+
Role of haemoglobin
- delivers oxygen to tissue
- acts as a buffer for H+ ions
- Co2 transport
Explain the stem cell process
- multipoint haematopoetic cell
- common myeloid progenitor cell (CMP)
- common lymphoid progenitor celll (CLP)
What do CMP cells become
- erythrocytes
- platelets
- macrophages
- basophils
- eosinophils
- neutrophils
What do CLP cells become
- NK cells
- b cells
- t cells
B cells further differentiate into what?
- plasma cells
What happens to red blood cells as they mature?
- they become smaller in size
Where is hypoxia sensed and what is the consequence
- sensed in the kidney
- erythropoietin hormone secreted
- stimulation of RBC formation
Where does normal RBC breakdown occur
- the spleen or liver
Explain RBC breakdown
- haemoglobin - heme and globin
- globin - amino acids
- heme - porphyrin (bilirubin) and iron
What is heme broken down to
- porphyrin (bilirubin)
- iron
Glycolysis role in the formation of RBC
- Generates ATP
- generated NADH (Prevents Fe2+ oxidising to Fe3+)
- free radical formation
Free radical formation may cause what?
- dangerous
- can cause Fe2+ to become Fe3+
- can damage cell membrane
- NADH acts as an electron donor to prevent Fe oxidation
Name a reactive oxygen species
- hydrogen peroxide
What is the risk associated with hydrogen peroxide
- damage to proteins
What is vital for protection of hydrogen peroxide (reactive oxygen species)
- glutathione (GSH)
- Forms water and an oxidised GSH (GSSG)
How is oxidised glutathione regenerated to glutathione
- NADPH
What is the rate limiting step in the hexose monophosphate shunt
- G-6-PD
- Glucose 6 phosphate dehydrogenase
Role of NADPH in GSSG
- Recycles to for GSH
How is carbon dioxide transported
- dissolved
- carbamino compound in Hb
- bicarbonate
What enters the RBC when CO2 leaves in order to preserve the potential
- Cl-
Explain the oxygen dissociation curve
- sigmoid
- allosteric cooperative binding
- a drop in Po2 at a lower level results in a greater % saturation drop than a higher
What can cause the oxygen dissociation curve to shift to the right and what will that cause
- increase in temp
- decrease pH
- Increase 2,3-BPG
- causes oxygen to be released at a tissue level
- lesser % saturation bound
What can cause the oxygen dissociation curve to shift to the left and what are its consequences
- decrease temp
- increaser ph
- decreased 2,3-BPG
- Less o2 released at same PO2
- Greater % saturation bound
Describe fetal Hb compared to adult
- 2 alpha and 2 gamma
- greater o2 saturation in haemoglobin at the same o2
Explain the affect of 2,3-BPG on the oxygen dissociation curve
- increased 2,3BPG = Shift to the right
- more released
- less bound
- decreased 2,3-BPG = shift to the left
- less released
- more bound
What affect on 2,3-BPG will occur in chronic anaemia?
- up regulation
What is termed the machinery of RBC
- The erythron
Raw materials of RBC production
- iron
- b12
- folate
What is released from the kidneys due to low oxygen levels
- erythropoietin
Which stem cell has the higher self-renewing ability and why is that useful
- the long term stem cells
- good for transplant patients
Pathway of RBC production from pronormoblasts
- pronoromblast
- early normoblast
- intermediate normoblast
- late normoblast
- reticulocyte
- erythrocyte
Why is iron essential?
- oxygen transport
- electron transport
- present in haemoglobin, myoglobin, enzymes
Iron dangerous?
- oxidative stress
- free radical formation
Where does iron absorption take place?
- in the duodenum
- uptake into cells of duodenal mucosa
What enhances iron uptake?
- haem irons
- ascorbic acid
- alcohol
What reduces iron uptake?
- tannins
- phylate
- caclcium
What reduces Fe3+ to Fe2+
- duodenal cytochrome B
What transports Fe2+ from the lumen of duodenum into duodenal cells?
- Divalent metal transport 1
What transports iron from the duodenal cell into the body?
- ferroprotein
What regulates iron
- hepcidin
- negative regulator
- levels decrease in anaemia = increase iron absorption
How can iron status be analysed?
- functional iron (hb concentration)
- transport iron (transferrin saturation)
- storage iron (ferritin)
When might ferritin be increased?
- inflammation or malignany
- increased in anaemia of chronic disease
Microcytic anaemias are deficiencies in _____ synthesis
- haemoglobin
What is sideroblastic anaemia?
- excess iron build up in the mitochondria and not incorporated into haemoglobin
How is iron deficiency anaemia defined?
- anaemia + low iron
Explain pathophysiology of anaemia of chronic disease?
- increased ferritin
- increased plasma hepcidin
- decreased iron release from macrophages
Causes of primary iron overload
- hereditary haemochromatosis
Explain hereditary haemochromatosis?
- HFE gene
- increased Hepcidin
- increased iron absorption
Treatment of primary haemochromatosis?
- venesection
Treatment of iron overload?
- iron chelating agents
e. g. desferrioxamine
