Haematology (4-7) Flashcards

Question

How are blood clots removed?

Answer 1

Fibrinolytic mechanisms → depend on digestion of fibrin by the protease plasmin → present in plasma as an inactive precursor - plasminogen - activated by a rage of factors particularly tissue plasminogen activator tPA

Answer 2

The formation of blood cellular components → highly organised differentiation process → ordered expression of different sets of genes → controlled by growth factors in the environment of the developing blood cell (the bone marrow in adults) → all blood cells are derived from haematopoietic stem cells

Answer 3

5 x 10^11 blood cells daily → mature blood cells have short lifetimes so need to be constantly regenerated → accelerated when there is haematological stress e.g. infection - need more leukocytes, high altitude - need more RBC

Answer 4

At a very early stage in embryonic development - about 3 weeks At this time the embryo separates into 2 sets → one generating the embryo proper and all the tissues of the adult → one forming the yolk sac - mesoderm the site where blood cells and blood vessels are first formed → first genetic switch at ~8 weeks - liver starts to produce blood cells → as you start to make bones in a developing foetus you start to switch blood cell production to the bone marrow

Answer 5

Mesoderm derived multipotent cells → differentiate to form (nucleated) red blood cells and endothelial cells - which generate a capillary system (plexus) within the yolk sac → at the same time the heart and aorta start to form - join up with the capillary plexus and the erythrocytes start to circulate

Answer 6

The later stage of embryogenetic haematopoiesis (before its 'primitive erythropoiesis' in the yolk sac) → occurs mainly in the liver and at birth switches to the bone marrow → produces entire range of blood cells you would find in an adult

Answer 7

Haematopoietic cells → form blood cells Stromal cells → provide support functions for the haematopoietic cells, provide the specialised environment for haematopoiesis to occur Osteoblasts → produce bone Osteoclasts → break down bone

Answer 8

Framework to hang muscles from Where haematopoiesis occurs Source of skeletal rigidity Reservoir of Ca2+ and PO43-

Answer 9

When you're born all of your bones produce blood cells → as you age haematopoiesis occurs in less bones → in adults ribs, pelvis, skull produce blood cells Can go wrong → you can lose regulation of where you produce blood cells

Answer 10

Bone is a specialised form of connective tissue with a rigid ECM → rigid outer layer of dense compact cortical bone - consists of closely pacts circular osteons around central Haversian canal - high levels of vascularisation (important fro transporting newly made cells) → inner core is less dense 'spongy' bone - has holes - find bone marrow → ends called epiphysis, central section is called diaphysis → has medullary cavity - find bone marrow here

Answer 11

Bone marrow transfusion contained haematopoietic stem cells (HSC) → HSC are capable of self-renewal → however it was found that they eventually stop working - have a limit called 'Hayflick limit' - due to telomeres → HSC are not infinite

Answer 12

BM cells were radiated - not enough to kill cells but enough to cause minor chromosome alterations → causes distinct marker so you can track lineage They found the markers to be present in all cells → i.e. one cells drives entire lineage Also found restrictive lineage → i.e. another stem cell drives lineage further along Allowing for the collusion that theres a single haematopoietic stem cell → and stem cells with restricted lineage also (common lymphoid and myeloid progenitor cells)

Answer 13

CD34 → other cells also express CD34 (e.g. endothelial cells) so not unique to HSCs

Answer 14

In 2 locations (niches) in the bone marrow → CD34 line the endosteum (boundary between solid bone & marrow) associated with osteoblasts → the perivascular region around vascular sinusoids Hence 'endosteal' and 'vascular' niches → endosteal - contains long-term slowly dividing HSCs which maintain the vascular niche HSCs → vascular - HSCs more actively dividing and progenitor cells are produced

Answer 15

Within its niche - regulated by many proteins (signalling molecules) → mediated through; direct contact, soluble factors and intermediate cells → as soon as it divides - sister cell in different environment - receives different signals (also asymmetric division loads cell differently)

Answer 16

*In vitro* culture of bone marrow cells → add growth factors and cytokines - monitor proliferation → better ethically

Answer 17

The process of making red blood cells → RBCs go through many phases MEP → pro-erythroblast → erythroblast → reticulocyte → erythrocyte Reticulocyte → non dividing, nucleus condensed and inactive, its process is to remove nucleus

Answer 18

The generation of platelets → stimulated by thrombopoietin (TPO) and other non-specific growth factors → TPO produced constitutively mostly by liver → inflammation can double product by liver via cytokine IL-6 → in thrombocytopenia (reduced platelets) BM stroll cells also produce TPO - platelets have TPO receptors so remove TPO from circulation

Answer 19

In 1818 Dr. James Blundell, a British obstetrician performed the first successful blood transfusion of human blood for treatment of a postpartum haemorrhage → used patient's husband as donor - extracted 4 ounces from his arm → he performed 10 transfusions - 5 were successful → also developed instruments for transfusion

Answer 20

In 1900, he showed that serum from some individuals could agglutinate or hemolyze the red blood cells of certain, but not all, other individuals - other individuals' red blood cells were unaffected → worked out the different groups that would hemolyse each other and named these 3 type A, B, and C (today A, B and O)

Answer 21

The ABO blood group antigens are encoded by one genetic locus on chromosome 9 Has 3 alternative alleles for 1 gene: → 6 genotypes - AO, AA, BB, BO, AB, OO → 4 phenotypes - A, B, AB, O Isoagglutinogen → encodes enzyme - allele affects activity I^A → encodes N-acetylgalactosamine transferase I^B → encodes a modified enzyme - galactose transferase activity i^O → encodes non functional enzyme I^A gives type A (dominant) I^B gives type B (dominant) I^A I^B gives type AB (co-dominance) ii gives type O

Answer 22

The enzymes 'decorate' carbohydrates attached to lipids on the outside of red blood cells → H-antigen attached to sphingosine to form a glycolipid - group O → group A has Gal-NAc attached to H-antigen → group B has galactose attached to H-antigen

Answer 23

A subclass of glycolipids found in cell membranes Cerebroside → ceramide with a single sugar residue → major lipids in ectoplasmic leaflet go myelin Ganglioside → ceramide with a chain of sugar residues → many of the sugar residues are -ve charged → particularly abundant in nerve cells → also found on epithelial cells in GI tract

Answer 24

By their expression on the red blood cell surface and the antibodies in the plasma Group A → anti-B antibodies Group B → anti-A antibodies Group AB → no antibodies Group O → anti-A and anti-B antibodies

Answer 25

Group O → agglutinates with neither blood antibody Group A → agglutinates with Anti-A Group B → agglutinates with Anti-B Group AB → agglutinates with both → blood transfusion will work if a person who is going to receive blood has a blood group that doesn't have antibodies against the donor blood's antigens

Answer 26

Indicate the presence of antibodies against red blood cells → used in paternity testing

Answer 27

Other genes are at play (e.g. A and AB parents having O child) → H is epistatic to I - expression of one gene modifies by the expression of another → individuals homozygous for h don't have FUT1 a fructose transferase - the products of ABO cannot be formed - if you're missing H then the ABO genotype doesn't matter (Bombay phenotype)

Answer 28

The present or absence of water soluble;e A and B (ABO blood group) antigens present in body secretions → people who secrete them into bodily fluids are known as secretors Secretor → Se/Se or Se/se Non-secretor → se/se → independent of blood type → encoded by gene FUT2 Non- secretors have increased risk of → oral disease, asthma, diabetes, alcoholism, infections, autoimmune diseases

Answer 29

AB+ → has no ABO antibodies (group O can donate to anyone)

Answer 30

Rhesus (Rh) antigens are transmembrane proteins expressed on erythrocyte cell surface → encoded by *RHD* (D antigen) and *RHCE* (Cc and Ee antigens) genes → Rh + = both *RHD* and *RHCE* → Rh - = deleted *RHD* Ce → Rh antigens are highly immunogenic 85% European ethnict are Rh+ → Rh/Rh or Rh/rh

Answer 31

Occurs if the mother is RhD- and 1st foetus is RhD+, their subsequent pregnancy can be affected → RBC from RhD+ foetus leak into the maternal circulation during birth → leads to production of anti-RhD IgG postpartum → in subsequent pregnancy IgG crosses placenta into foetal circulation - RhD+ foetus affected

Answer 32

Mother receives anti-Rh antibody to prevent immunisation Child receives blood transfusion with compatible blood

Answer 33

When the mothers blood type is O and the baby's is A or B → mothers immune system may react and make antibodies to the foetus red blood cells → anti-A and anti-B are IgMs and seem to be important in early pregnancy → can reduce or abolish the Rh incompatibility

Answer 34

Compatibility testing Anticoagulant solutions (lining glass with sodium citrate) Preservative solutions (CPD-A1 - citrate, phosphate, dextrose, adenine) Refrigeration Blood banks Venous access Plastic blood bags Component administration Infectious disease testing (NAT - nucleic acid and ELISAs) High-risk donor screening

Answer 35

Formation of blood vessels as a consequence of trauma, embolism, cancer, diabetes or regeneration of endometrium after menstruation or just growth → endothelial cells grow in an ordered manner to generate new vessels (often have CD34 marker) → 2 types: sprouting or intussusceptive

Answer 36

When a 'sprout' of solid endothelium grows out from a single capillary → lumen follows creating two capillaries

Answer 37

When a single capillary forms a set of endothelial cells down the middle → ultimatelt forming 2 lumens

Answer 38

Usually ischaemia (lack of blood supply) which results in hypoxia (reduced O2) and lack of glucose → ischaemia occurs in growing tissues which out-strip the blood supply - or where the blood supply is compromised Hypoxia stimulates the expression of genes for pro-angiogenic factors (when O2 is plentiful the genes are shut off) → hypoxia also stimulates EPO synthesis in kidney - proximal tubules have low O2 sensors - EPO release to bone marrow increases RBC

Answer 39

Hypoxia-inducible factor (α and β) → activates transcription of genes for pro-angiogenic factors (main one VEGF) → HIF is destroyed by the presence of O2 - hypoxia induces angiogenesis

Answer 40

Vascular endothelial growth factor - main pro-angiogenic factor → binds to its receptor tyrosine kinase expressed only by endothelial cells and drives proliferation In presence of O2 VHLp binds HIF-α and drags to proteasome → VEGF switched off In hypoxia VHLp doesn't bind HIF-α allowing it to dimerise with HIF-β → change in structure reveals nuclear localisation sequence → binds DNA just infant of VEGF promoter → VEGF transcription induced → growth of endothelial cells

Answer 41

Formation of arteries due to stress sensing → most common reason is that blood flow is obstructed in an artery - through a lump (e.g. embolism) blocking or narrowing (atherosclerosis) New arteries develop from pre-existing anastomosing arterioles (small channel joining two larger channels) → due to the obstruction blood flow transfers from the main arteries to the anastomosing arteries - in response they enlarge

Answer 42

Mechanical (not ischaemia) acting on the endothelium lining of the arterioles → particularly through increased shear stress because of the increased blood flow in the anastomosing arteries (due to blockage in main arteries) → shear stress detected through stretching of plasma membrane - transmitted into cell interior via cytoskeleton → this indirectly activates a bundle of genes (40+) VEGF not involved - encoding growth factors and adhesion molecules - driving proliferation of endothelial cells and other cells in th tunica media Exercise stimulates blood flow and so arteriogenesis

Answer 43

Blood disorders where there are fewer than normal pf specific cell types → e.g. lack of erythrocytes is an anaemia

Answer 44

Anaemia = a reduction in numbers or functionality of erythrocytes → leads to a reduction in the amount of O2 carried by the blood → characterised by paleness and fatigue → can be caused by bleeding, genetic disorders, leukaemia Aplastic anaemia → too few cells Iron deficiency anaemia → haemoglobin defect Pericious anaemia → vit B12 deficiency

Answer 45

A group of inherited conditions that affect haemoglobin - produce little to none → treatment: difficult server - blood transfusion or stem cell transplant (anaemia not sorted with nutrition)

Answer 46

Failure of erythropoiesis → the malignant cells displace the erythroid recourses from their bone marrow niches disrupting the lineage

Answer 47

Conditions where the white blood cell types may be reduced in number e.g. neutropenia → neutrophils reduced - leads to susceptibility of infection thrombocytopenia → reduction in platelets - leads to bleeding

Answer 48

Neoplasia (uncontrolled growth) in blood and blood-forming tissue → leukaemia - bone marrow → lymphoma - lymph node → myeloma - bone marrow

Answer 49

Abnormal cells arise in the bone marrow → stem cell niches in the BM become occupied with abnormal stem cells - normal cell production squeezed out → proliferating abnormal cells spill over into the circulation where they don't divide - need the niche for proliferation

Answer 50

Abnormal cells arise in the lymph nodes and proliferate there - can spread to other lymph nodes destroying their functions (and other tissues including bone marrow) Non-hodgkin lymphomas → B-cell neoplasia (precursor or mature), T-cell and NK-cell neoplasms (precursor or mature) and Hodgkin lymphomas → two nuclei - loss of apoptosis, leads to inflammatory response