Fundementals of blood and RBC's Flashcards
what is blood
has a cellular component and an extra-cellular matrix liquid component which is blood plasma
what is plasma
- blood plasma is yellow
- consists of mainly water, biomolecules and inorganic compounds
what does blood transport
nutrients
proteins,hormones, antibodies
removes metabolic waste
what do inorganic salts do in the blood
buffer the pH and contribute to osmotic balance and the regulation of the cell membrane potential
what are erythrocytes
RBC’s
what do erythrocytes do
transport O2 and CO2 around the body
what is a haematocrit
the % of red blood cells relative to total blood volume
what are leukocytes
WBC’s
what are examples of leukocytes
basophils, eosinophils, neutrophils, lymphocytes, monocytes
what are platelets made from
cytoplasmic cell fragments of cellular precursors
what are platelets
essential for blood clotting
what are characteristics of the RBC
- flexible disc
- biconcave shape
- no nucleus
- reduced number of organelles and cellular membrane structures
- short life span
what is the lifespan of a RBC
120 days
what is the overall structure of the RBC
plasma membrane
biconcave shape
what are features of the plasma membrane
- asymmetrical
- negatively charged phospholipids
- located on the inner part of the lipid bilayer
- important for cell signalling communication
what are features of the biconcave shape
- spectrin has a filamentous shape
- primary component of the RBC cytoskeleton
what do spectrin gene abnormalities cause
spherical and fragile RBC’s
what is the clotting process
- platelets come in contact with collagen fibers
- platelets will then swell and form a sticky patch which begins the blood clotting cascade
prothrombin and fibrinogen are cleaved to thrombin and fibrin leading to the formation of a blood clot prior to the formation of scar tissue in wound healing
what are platelets released by
released by megakaryocytes
what do platelets do
contain enzymes that initiate blood clotting
what is the site of erythropoiesis
bone marrow
takes place in haematopoietic or red marrow which is located within trabecular bone at the end of long bones
what does erythropoiesis do
RBC production =RBC volume / RBC lifespan
what drives erythropoiesis
Erythropoiesis is driven mainly by the hormone erythropoietin (EPO), which is a glycoprotein cytokine.
what does EPO do
- In response, there is a surge in EPO production, which acts on the bone marrow to stimulate increased red blood cell production.
- all erythroblasts are EPO dependent then after they are iron dependent
- when EPO binds to an EPO receptor it causes cell proliferation and cell differentiation
what are reticulocytes
an immature red blood cell without a nucleus
what does an elevated number of reticulocytes mean?
An elevated number of reticulocytes indicates active bone marrow response to blood loss through trauma or anaemia
how do reticulocytes form
When haemoglobin synthesis has been completed the erythroblast nucleus, that has been progressively condensing, gets expelled yielding the reticulocyte
what is HbA or adult haemoglobin
Consists of four subunits, two identical α chains and two identical β chains
what is HbF or fetal haemoglobin
consists of two identical α chains and two identical γ chains.
what is the main secondary structure of the haemoglobin protein subunits.
α-helix
what is the structure of haemoglobin
Four heme groups are bound to each of the subunits.
what does haemoglobin do
Binds and transports O2 around the body.
what which haemoglobin has a higher affinity for O2
HbF
what gives haemoglobin its red colour
heme group
what does heme do
- Fe atom (Fe2+), which binds oxygen.
- When O2 binds to heme there is a partial transfer of an electron from Fe to O2 yielding Fe3+ and a superoxide ion (O2-
why is the haemoglobin subunits there
The haemoglobin protein subunits ensure that O2 and not O2- is released in tissues.
what is cooperative binding behaviour
- O2 binding to one heme group increases the possibility of O2 binding in the other three heme groups.
- Therefore, the unloading of O2 from one heme groups assists the unloading of O2 from the other three heme groups.
what does 2,3-DPG do
Lowers the affinity of O2 for haemoglobin, ensuring the release of O2 in tissues.
what is the molecular mechanism of 2,3 BPG/ 2,3-DPG
- 2,3 BPG is an allosteric (connection away from active site) regulator of haemoglobin. It binds to the centre of the tetramer (molecule w 4 subunits) at a site different from the O2 binding ones.
- Causes haemoglobin conformation with lower O2 binding affinity – where more O2 binding sites are occupied.
- Lower O2 binding affinity ensures easier O2 release
what is the binding like for 2,3-DPG for HbF
- Consequently 2,3-BPG does not bind HbF as efficiently as it binds HbA.
- Fetal RBCs have higher affinity for O2 than maternal RBCs.
what is the affinity of myoglobin like
It has a higher affinity for oxygen compared to haemoglobin → inefficient/low oxygen release.
how des CO2 affect pH
how does CO2 react with terminal amino groups
Carbon dioxide reacts with the terminal amino groups of deoxyhaemoglobin and forms “carbamate” groups.
HCO3- transport across the RBC plasma membrane is coupled with transport of Cl- in the opposite direction.
what happens when CO binds to haemoglobin
binds to haemoglobin at the oxygen binding site yielding carboxyhemoglobin
what does CO do to O2 in the haemoglobin
- displaces bound oxygen
- CO binding to one of the 4 heme groups will increase haemoglobin affinity for oxygen
what are the CO-poisoning symptoms
Disorientation
Nausea
Lethargy
Weakness
what hypovolaemia
- Loss of extra-cellular fluid.
- Can be attributed to loss of blood volume.
what are the causes of hypovolaemia
- Excess bleeding due to trauma.
- Diarrhea or vomiting.
- Renal failure.
- Use of diuretics.
what are symptoms for hypovolamia
Fatigue, headaches, cyanosis, tachycardia.
what happens if you leave hypovolaemia untreated
hypovolaemic shock, organ failure and death.
what is anaemia
Reduced haemoglobin concentration → reduced oxygen transport.
what are the clinical symptoms for anaemia
tachycardia, breathlessness, pallor, lethargy.
what are the causes of anaemia
- iron deficiency
- Bone marrow suppression –
- Blood loss.
- Folate deficiency
- Haemolysis
- Inherited problems in haemoglobin synthesis
- Autoimmunity
what is sickle cell anaemia caused by
- → β-globin position 6 glutamate replaced with valine
- → production of HbS
- → oxyhaemoglobin is not affected but deoxyhaemoglobin becomes fibrous and forms aggregates.
what do RBC’s look like in sickle cell anaemia
- sickle-like shape, which clog capillaries and prohibit smooth blood flow.
- RBCs stick frequently to vessel walls and remain in blood circulation for a reduced amount of time.
what is α-thalassaemia caused by
caused by deletion/inactivation of three or four of the α-globin genes
what is the deletion/inactivation of 3 genes
HbH disease → enlarged spleen/liver, anaemia (may require blood transfusions), haemolysis.
what is the deletion/inactivation of 4 genes
Hb Bart syndrome → embryonic lethality.
what is β-thalassaemia caused by
caused by mutations or deletions of the β-globin gene.
what does β-thalassaemia cause
Anaemia, haemolysis, erythroid hyperplasia, bone marrow expansion, extramedullary haematopoiesis.
what is polycythaemia caused by
Decrease in blood volume.
increased RBC production entering circulation – erythrocytosis
Polycythaemia is an example of a myeloproliferative neoplasm
what is polycythaemia characterised by
elevated haematocrit
what are the symptoms of polycythaemia
Fatigue, dizziness, headaches
Gum bleeding, nosebleeds
Can affect heart function, spleen function, blood clotting.
