What is the structure of erythrocytes? What is their lifespan? Where are they removed?
- Simple cell, anucleate, discoid, biconcave disc
- Live for 100-120 days
- O2/CO2 carrier
- Contain haemoglobin and glycolytic enzymes
- Formed: adults = bone marrow of axial skeleton, children = all bones, foetus = liver, spleen and yolk sac
- Removed in spleen, liver, bone marrow + through blood tests
- Reticulocyte = immature RBC, not usually found in blood
What is the structure of haemoglobin? What is its role?
- Tetrameric protein with 4 globin chains, each with haem group (porphyrin with Fe2+) = capable of reversibly binding oxygen
- Several haemoglobin types:
- Haemoglobin: 2 alpha and 2 beta chains
- Foetal haemoglobin: 2 alpha and 2 gamma chains, means it has a higher affinity for oxygen
- HbA2: 2 alpha and 2 sigma chains
- Carries oxygen from lungs to tissues
What is haemopoeisis? How are RBCs, WBCs and platelets produced?
- Haemopoeisis = formation of new blood cells and platelets. Adults = precursors of mature cells derived from bone marrow of axial skeleton, but all bones in children. Embryos = in yolk sac, liver, spleen + bone marrow. Stem cells = pluripotent so can differentiate into RBCS, WBCs or platelets.
- RBC production = erythropoeisis
- WBC production = myelopoeisis
- Platelet production = thrombopoeisis
What are the hormonal factors in erythropoeisis, myelopoeisis + thrombopoeisis?
- Erythropoeisis = hormonal stimulating factor = erythropoeitin, made in kidneys
- Myleopoeisis = hormonal factor = granulocyte-macrophage colony stimulating factor, will only stimulate production of myeloblastic WBCs + not lymphoid cells
- Thromobopoeisis = hormonal factor = thrombopoeitin, leads to prodcution of megakaryocytes, which platelets bud from
What are leukocytes? What is their role? What are the different types?
- Leukocytes = white blood cells
- Two main groups, granulocytes + lymphocytes
- Both involved in immune response, innate = granulocytes, adaptive = lymphocytes
- Neutrophil = most abundant WBC, phagocytic and release chemo- + cytokines to induce inflammation. Multi-lobed nucleus, lasts ~10 hours. Granulocyte colony stimulating factor is the regulating hormone for most leukocytes (all the phils)
- Monocytes = reniform (kidney bean-shaped) nucleus, mature into macrophages which then become tissue resident (common macrophages you should know: Kupffer cells, alveolar macrophages, osteoclasts), lasts 8-12 hours
- Basophils = bi-lobed nucleus, very prominent dark blue granules of histamine, lasts 8-12 hours. Mature into mast cells, express IgE + release histamine. Mast cells are almost identical to basophils except are tissue-resident and come from a different cell lineage
- Eosinophils = bi-lobed nucleus that is 'lozenge-shaped', distinct granules, lasts 8-12 hours. Role in fighting parasitic infections but also wide range of regulatory functions
- Lymphocytes - 'fried egg appearance', comprise B and T cells (B cells mature in bone marrow, T cells mature in thymus gland). B lymphocytes = plasma cells/memory cells + produce antibodies, T lymphocytes = T helper, T cytotoxic, T suppressor. Lasts 8-12 hours
What do the terms haematocrit, anaemia and haemophilia mean?
- Haematocrit = percentage of RBCs in cellular component of blood
- Anaemia = reduced Hb, often due to iron deficiency. Two types: impaired production + increased haemolysis
- Haemophilia = inability to make blood clots due to factor VIII deficiency (Haemophilia A) or Factor IX (Haemophilia B), A more common
What are the causes and symptoms of anaemia?
- acute blood loss (haemorrhage)
- production mismatches - hypoplastic (not enough), dyshaematopoeitic (ineffective production)
- increased removal of RBCs - haemolytic anaemia
- deficiencies of iron, folate (macrocytic anaemia) or vitamin B12 (pernicious)
What is haemostasis? Why is blood fluid inside vessels?
- Haemostasis = the process to prevent + stop bleeding, is mediated by coagulation (where blood changes from liquid to gel/solid, also known as clotting, 3 main mechanisms = vascular constriction, platelet plug formation and clot formation)
- Blood should remain fluid inside vessels, should clot when outside
- Blood = fluid inside vessels as platelets + proteins of coagulation cascade circulate in inactive state, endothelial cells, anticoagulant pathway + fibrinolytic pathways ensure fluidity
- Bleeding = blood fails to clot outside vessel
- Thrombosis = clotting inside vessel
What are platelets? Where do they originate from? What is the regulatory hormone? What are the two types of granules?
- Platelets = 2-5um, last 7-10 days, circulate in inactive form + anucleate and discoid but become spiculated with pseudopia once activated, form blood clots (coagulation cascade)
- Originate from megakaryocytes, 1 megakaryocyte = 4000 platelets = membrane blebbing process
- Regulatory hormone = thrombopoeitin - produced by liver + kidneys
- Plasma have 2 types of granules: alpha (coagulation factors, fibrinogen and other clotting mediators) and dense (ADP + platelet-activation mediators)
What is plasma? Which proteins does it contain? What is serum?
- Plasma = fluid component of blood (55%)
- Transport medium containing water, salt, glucose + proteins
- Albumin = produced in liver, determines oncotic pressure of blood, keeps intravascular fluid within that space, lack of albumin leads of oedema
- Carrier proteins
- Coagulation proteins. These are all prodcued by the liver
- Immunoglobins = produced by plasma cells, key role in immunity + vaccination
- Serum = plasma without clotting factors
What are the two main systems of erythrocyte antigens?
ABO and Rhesus
What are the 4 blood groups of the ABO blood group system?
- A: A antigen, dominant, 40%, has anti-B antibodies, means you don't attack own cells
- B: B antigen, dominant, 12%, has anti-A antibodies
- AB: A + B antigens, universal acceptor, 3%, no antibodies. AB+ is universal plasma donor as no antibodies in plasma
- O: universal blood donor, 45%, no antigens but anti-A + anti-B antibodies. O- = universal blood donor
- ABO antigens made from carbohydrates
- A, B, AB + O are either Rhesus + or Rhesus -. Rh + contains D-antigen + no antibodies. Rh - contains no antigens, has anti-D antibodies
- When looking at recipient, focus on antibody
- When looking at donor, look at antigens
What are ABO antibodies generally a mixture of?
- Mixture of IgM + IgG antibodies. IgM antibodies don't cross placenta but IgG (Rhesus) antibodies do
What are the Resus antigens?
- Series of C, D + E antigens, D = most important
- High proportion of D negative people will form Anti-D if exposed to D positive blood, can cause Rhesus disease
What is Rhesus disease? How can this be treated?
- D negative woman with D positive father, if baby's Rhesus D positive antigens cross placenta then mother makes anti-D antibodies that can destroy baby's erythrocytes by attacking D antigens, baby can become anaemic. As this is first time mother has been exposed to Rh+, baby will be okay. Subsequent baby with Rh+ blood will be affected (Rhesus disease)
- Treatment = anti-D immunoglobulin injections, prevents mother from making her own anti-D antibodies
How do we perform ABO and Rh D grouping?
- Forward typing = patient's RBCs mixed with anti-A, anti-B and anti-D (separately). If antibody binds to antigen in blood, colour change
- Reverse typing = patient's plasma, add known red blood cells (A or B). Adding know antigen, looking for antibody
What are the the three rules to help remember what blood groups can donate to and receive?
- Group O = no antigens = universal donor
- Group AB = both antigens = universal recipient
- Negative can donate to positive but positive can't donate to negative
- O- can donate to all, can receive O- only
- O+ can donate to AB+, A+, B+ and O+, can receive O- and O+
- A- can donate to AB-, AB+, A+ and A-, can receive O- and A-
- A+ can donate to AB+ and A+, can receive O-, O+, A- and A+
- B- can donate to B-, B+, AB- and AB+, can receive O- and B-
- B+ can donate B+ and AB+, can receive O-, O+, B- and B+
- AB- can donate to AB- and AB+, can receive O-, A-, B- and AB-
- AB+ can donate to AB+, can receive from all
What is a Direct Antiglobulin Test (DAT)?
- Some RBCs may already be coated in antibodies, this method detects them
Which non-RBC components are used in transfusions?
- Plasma = can be used as fractionated to produce specific components
- White blood cell = rare due to antibiotics that work
- Fresh frozen plasma = contains coagulation proteins + clotting factors, from male donors only
- Platelets = used in thrombocytopaenia (low platelet count), ABO type still important even though platelets don't have red cell antigens as there will be some plasma within unit that contains RBC antibodies)
- Cryoprecipitate = made by thawing out FFP. Rich in fibrinogen, used in DIC and massive transfusion if there is a lack of fibrinogen required for aggregation + precursor to fibrin in coagulation cascade
- Intravenous immunoglobulin (IVIg) = made from large pools of donor plasma, contains antibodies to common circulating viruses (normal IVIg), can also be specific (from pateint who's had disease)
- Albumin = used in cases of oedema to correct oncotic pressure of blood
- Anti-D globulin = collected from people sensitised to D + used to prevent Rh D disease
How can we try and avoid transfusion?
- Optimise patients with planned surgical procedures pre-op
- Use of erythropoeitin stimulating drugs
- Cell salvage (re-infusing own blood lost in surgery)
- IV iron for severe iron deficiency
What does gastrulation mean (embryologically)?
- Mass movement + invagination of the blastula to form 3 layers - ectoderm (skin, nervous system, neural crest which contributes to cardiac outflow), mesoderm (all types of muscle) + endoderm (gastrointestinal tract)
- Most of cardiovascular system derived from cells that were situated in mesoderm. Some contribution from cardiac neural crest cells from ectoderm
What are the two heart fields on day 15?
Have no cardiac function. First heart field (red) = future left ventricle. Second heart field (yellow) = outflow tract, future right ventricle, atria
What happens to the heart fields between day 15 and day 50?
First heart field generates a scaffold which is added to by second heart field and cardiac neural crest. 4 chambers by day 50
What do the terms gene and transcription factor mean?
- Gene = DNA which when expressed is transcribed into RNA which is translated into protein with a function
- Transcription factor = type of protein which when expressed 'turns on/off' many other gene(s) expression. In heart formation, examples = GATA, Tbx, Fog-1 (expressed in different parts of heart depending on whether they come from FHF or SHF)
What are the 3 stages of cardiac formation?
1. Formation of primitive heart tube
2. Cardiac looping
3. Cardiac septation
What happens in the formation of the primitive heart tube?
- During 3rd week, heart formed from cells that form horseshoe shaped region called cardiogenic region
- By day 19, two endocardial tubes form, fuse to form single primitive heart tube
- Day 21, embryo undergoes lateral folding, the two endocardial tubes fused to form single heart tube
- Learn these parts of primitive heart tube and what they become:
- Truncus arteriosus = ascending aorta, pulmonary trunk
- Bulbus cordus = smooth (outflow) parts of L + R ventricles
- Primitive ventricle = forms majority of ventricles
- Primitive atrium = both auricular appendages, entire L atrium, anterior part of R atrium
- Sinus venous = smooth part of R atrium, vena cavae, coronary sinus
What happens in cardiac looping?
- Bulbis cordis moves inferiorly, anteriorly + to embryo's right
- Primitive ventricle moves to embryo's left side
- Primitive atrium + sinus venosus (bottom part of heart) move superiorily + posteriorly
How does the body know which way is left?
- All vertebrae hearts have a leftward ventricle
- During development, the node secretes nodal, which circulates to the left due to ciliary movement. This switches on transcription factors that cause looping
What happens in cardiac septation?
- At this stage, one common atrium + one common ventricle connected by internal opening called the atrioventricular canal
- Masses of tissue called endocardial cushions grow from the sides of the atrioventricular canal to partition it into two separate openings
- Superior + inferior endocardial cushions fuse, forming two separate openings (left and right atrioventricular canals)
Picture summary of the development of the heart.