Haematology Flashcards
What is plasma
Liquid component of blood.
What is the buffy coat comprised of
Leukocytes and platelets
order of plasma protein abundance and how to test
Test by electrophoresis. Serum albumin most abundant (at positive anode) then globulins: alpha 1, alpha 2, beta 1, beta 2, gamma)
What is serum
Plasma minus clotting factors
Order of fluids in body from most to least
Intracellular, extracellular/interstitial fluid, blood plasma, then cellular fluid
Name the functions of plasma
Clotting ( clotting factors and Von willebrand) , Immune defence (antibodies and complement proteins) , osmotic pressure maintenance (albumin ), metabolism ( glucose AA’s and vitamins transported in plasma), Endocrine (Many hormones soluble in plasma), Excretion (Cell metabolism waste products travel in blood like urea)
Serum albumin production, functions
Produced by the liver.
Transports lipids, hormones and ions
Maintains osmotic pressure of plasma
Albumin transports fatty acids released from triglycerides in lipolysis, for tissue use
Difference between preparing plasma and serum
Plasma is relatively quick - add an anticoagulant and spin
Serum is taken into a tube without an anticoagulant allowed to clot then centrifuged so takes a little bit longer but a silica coat will form between the two layers making it a cleaner sample
Alpha 1 globulin production and functions
A1AT is produced by the liver, it inhibits proteases and protects tissues from enzymes especially neutrophil elastase which is released by neutrophils during inflammation and damages tissues.
What does deficient A1AT cause
Degradation of lung tissue leading to a loss of elasticity and respiratory problems. This type of globulin is the most vulnerable to inhaled pollutants
Example of alpha-2 globulins and their function
Haptogloblin which binds to the Haemoglobin release from red blood cells when they die, the spleen will remove the haptoglobin-Haemoglobin complex, it avoids toxic levels of oxygen which could produce radical species
Alpha-2 macros login is a protease inhibitor and can inactivate fibrinolysis, stops the breakdown of fibrin in blood clotting
Measuring what can help to diagnose haemolytic anaemia
Haptoglobin as more red blood cells are lysed and therefore haptoglobin is binding to more
Examples of beta globulins, their functions and where they’re produced
Produced in the liver
Beta globulins include C3 and C4 as well as transferrin
Transferrin transports dietary iron and iron for, ferritin stores
Gamma globulin examples and diagnostic use
Immunoglobulins and C reactive proteins
Large peak of gamma globulins indicate infection or myeloma
Role of Mg2+
Cofactor for many enzymes
How are intracellular and extracellular contents of plasma balanced
NA+ plentiful in the plasma whilst K+ is plentiful intracellularly. The positive charge from K+ inside the cell is balanced by extracellular Cl- and anions like proteins nuclei acids and phosphorylated proteins
Why is the NA/K ATPase pump significant
Needed to maintain functioning of electrically excitable cells like neutrons and muscle fibres. 1/3 of AT{ consumed during rest is to power this pump.
When ATP is depleted what happens to cells
Cells become more spherical and intracellular and extracellular concentrations change and NA+ and H2O move in
Name the three usages of plasma in regards to disease and disease protection and explain
Biomarkers- study of plasma proteome and it’s links with disease, medications and lifestyle to make treatment decisions. Elevated levels become biomarkers of disease
Passive immunotherapy- immunoglobulins can transfer immunity from on to another e.g take plasma from a donor: concentrate IVIG (intravenous immunoglobulin G) as IVIG contains large amounts of IgG antibodies so can protect against common pathogens the donor has been exposed to - good for lupus patients
3) Hyperimmune globulin - donors screened via ELISA for high levels of IgG against a certain pathogen, the IgG fraction is isolated and concentrated providing passive immunity to a specific pathogen for someone. Given after someone has high risk exposure to a pathogen like rabies, hep B, etc. vaccines provide active immunity but take weeks for a response.
Where do red blood cells come from and what from
From the bone marrow, derived from haematopoeitic stem cells which make lymphoid stem cells ( lymphoid progenitor) to make lymphocytes like T cell, B cell and NK cells and myeloid stem cells (myeloid progenitor) where erythrocytes, platelets, monocytes, granulocytes, basophils, eosinophils and mast cells are derived
What is haematopoeisis
Formation and development of blood cells
Two functions of haematopoeitic stem cells
Ability to self renew as daughter cells become the stem cells again
Can differentiate to mature progeny where the daughter cells follow a differentiation pathway
Order the differentiations of myeloid stem cells from longest life span and state their function
Erythrocyte longest about 120 days for oxygen transport
Platelet 10 days for Haemostasis
Monocyte few days for defence against infection phagocytoses and kills
Neutrophil 7-10 hours defence against infection phagocytoses and kills
Eosinophil less than neutrophil is against parasitic infection seen in allergies
Lymphocyte variable lifespan for humour also (b cells making antibodies) and cellular immunity (T cells directly killing)
Sites of haematopoeisis in foetus
At 3 weeks the yolk sac makes haematopoeitic stem cells
At 6-8 weeks the liver makes HSC expands and maintains supply
At 10 weeks the bone marrow develops haematopoeitic activity and this is where haematopoeitic activity will occur in adults ( pelvis, femur sternum)
What is haematopoeisis regulated by and disruption of this regulation leads to what
Regulated by genes, transcription and growth factors as well as the micro-environment
Disruption causes an in balance between proliferation and differentiation leading to leukaemia or bone marrow failure.
What are haematopoeitic growth factors
Glycoproteins that bind to cell surface receptor to regulate proliferation and differentiation of HSC. They regulate function of mature blood cells
Name the growth factor of erythrocytes
Erythropoietin
Name the growth factors of granulocytes and monocytes
G-CSF, G-M CSF, cytokines like IL’s
CSF is colony stimulating factor
From the lymphoid progenitor, T cell progenitors, B cell progenitors and NK progenitors arise: what is the difference between them
B and NK progenitors are located in the bone marrow. Whereas e T cell progenitors make T cells in the thymus which then move to the bone marrow.
T and NK cells are cytokine producing whereas B cells are antibody producing
Another word for platelets
Megakarytocyte
How does erythropoiesis occur
From the common myeloid progenitor arises a proerythroblast turns into (early, intermediate and late) erythroblasts and then reticulocytes and erythrocytes.
Down the line the nucleus and cytoplasm looking parts becomes more clear ( happens in bone marrow) then in the peripheral blood these become reticulocytes and erythrocytes. Reticulocytes still have some RNA and stain darker
Requirements for erythropoiesis
Folate, B12, Erythropoeitin, Iron
What will low folate, iron and B12 do to cells and what does it cause
Will cause anaemia.
If low iron then red blood cells will be microcytic (often in pregnancy, childhood or low iron resource nations)
If low B12 or folate then red blood cells will be macrocyctic ( due to alcohol excess, pregnancy or veganism )
What is erythropoietin secreted in response to
Hypoxia. Anaemia or hypoxia will stimulate EPO, EPO will stimulate the bone marrow to produce more red blood cells which removed the stimulus to make more red blood cells. Demand supply feedback loop
Function of Iron
Oxygen transport in blood, mitochondrial proteins like cytochromes a,b,c needed for ATP production and cytochrome P450 for hydroxylations
Iron absorption, what non heme contain and iron homeostasis
Iron absorbed in duodenum haeme Fe2+ ferrous form is best absorbed, non heme Fe3+ ferric needs reducing sources like cytochrome B or Vitamin C for absorption.
Excess iron is toxic to heart and liver so absorption is regulated by hepcidin which blocks iron absorption or liver releasing iron.
Iron is absorbed in heme ferrous 2+ form by dmt-1 but as the non heme ferric form can’t be absorbed cytochrome-b or vitamin c turns it into its ferrous form. once inside the cell it can bind to apoferritin forming a ferritin mycelle the change of Fe2+ to Fe3+ crystallises a protein shell this means lots of iron is stored here and will be pooped out as it a not reversible. Once entering the cell however if the iron is needed it can bind to ferroportin which absorbs Fe2+, this step can be inhibited by hepcidin. If not inhibited, hephaestin will convert the iron from the ferrous to ferric form, the ferric form will then bind to apotransferrin and pushed out of the cell
What can inhibit erythropoeisis other than low iron, B12, EPO and folate
IL-1, TNF-alpha, IL-6, IFN gamma can inhibit the secretion of erythropoeitin which is needed for erythropoeisis, it can also decrease responsiveness of erythroblasts to EPO. They can also increase hepcidin which can inhibit erythropoeisis can also result in anaemia as hepcidin stops Fe absorption, transport and availability.
Where is Vitamin B12 found
Meat, fish, eggs, liver, kidney, milk, cheese
Where is folic acid found
Green leafy vegetables, cauliflower, Brussels sprouts, liver and kidney, fruit, yeast
How is Vitamin-B12 absorbed
B12 in the stomach bound to R-protein which is called heptacorrin and this is so the stomach acid doesn’t digest it. Then in the small bowel (ileum) the R protein is digested and it binds to intrinsic factors which are made by parietal cells as intrinsic factors cant be digested. So now you have B12-IF complex which binds to cubulin in ileum to take it into the endothelial cells- the lining. Complex is broken down and B12 binds to transcoalamin II to be taken into blood and to the liver
Inadequate secretion of intrinsic factors is what
Pernicious anaemia
What can cause B12 deficiency
Inadequate diet-veganism, malabsorption in coeliac disease, lack of stomach acid- achlorhydia, inadequate IF secretion-pernicious anaemia
What do Vitamin B12 and Folate deficiency cause
DNA synthesis is inhibited
Both are needed to make dTTP which is a precursor of DNA. dTTP is used to make thymidine
Also affects any rapidly dividing cell so cells grow in bone marrow but can’t divide normally, epithelial cells of mouth and gut affected as cells rapidly divide to replace, gonad nerves are affected
Where is folic acid absorbed and when is more folate needed
Absorbed in small intestine, more needed during pregnancy and for conditions where more red blood cells need to be made like sickle cell anaemia and haemolytic anaemias
Where do blood products go after RBC destruction
Iron from Haemoglobin travels on the plasma bound to transferrin returns to the bone marrow. The heme is broken down into bilirubin and excreted
What does erythrocyte function depend on
Integrity of the membrane
Haemoglobin structure and function
Cellular metabolism
Defect causes haemolysis
Describe the red blood cell membrane
Are biconcave in shape to allow manoeuvrability
Membrane made of lipid bilayer supported by proteins and cytoskeleton contains transmembrane proteins to maintain integrity shape and elasticity of red cell
What do disruptions in vertical membrane linkages cause (ankyrin/spectrin) causes
Hereditary Spherocytosis
Cells will be round and lack central pallor, is the loss of cell membrane without same amount of cytoplasm so become round. Cells are less flexible and removed
What does the disruption of horizontal membrane linkages cause
Hereditary elliptocytosis
Shells become elongated
