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describe the structure of the red cell membrane
-outer hydrophilic region containing glycolipids, glycoproteins and proteins -central hydrophobic region containing proteins, cholesterol and phospholipids inner hydrophobic layer of mesh-like cytoskeletal proteins to support the lipid bilayer
what are integral membrane proteins?
proteins that extend from the outer surface and traverse the entire lipid bilayer membrane to the inner surface
what are the two major integral membrane proteins?
glycophorins (A, B and C) Band 3 (anion transporter)
give 3 other examples of integral membrane proteins
sodium/potassium ATPase
Aquaporin 1
Surface receptors such as TfR
what are peripheral membrane proteins?
proteins that bind to the cytoplasmic surface of the membrane and forms the red blood cell membrane
what is the role of the cytoskeleton?
acts as a framework to support the bilayer, maintains the biconcave shape and is responsible for deformability
name four major peripheral membrane proteins
actin
spectrin
ankyrin
protein 4.1
what is the role of spectrin?
Controls biconcave shape and deformability of the cell by binding with other peripheral proteins and forming a cytoskeletal network of microfilaments
what happens if spectrin becomes denatured?
red blood cell becomes spherical and loses its flexibility
what is the role of ankyrin?
anchors lipid bilayer to membrane skeleton by interacting with spectrin and Band 3
what is the role of Protein 4.1?
links the cytoskeleton to the membrane by associating with glycophorin stabilises the interaction of spectrin and actin
what is the role of actin?
responsible for contraction and relaxation of the membrane
blood group antigens
found on red cell membranes and determine our blood group
what is the function of red blood cells and how do they achieve this?
-main function is to transport respiratory gases to and from tissues -red blood cells travel the microvascular system without being damaged, retaining a shape that allows gaseous exchange -red cell membrane should be tough, yet flexible
what determines strength and flexibility of the red cell membrane?
cytoskeletal protein interaction with the membrane lipid bilayer
what happens if there is an increase in free plasma cholesterol?
accumulation of cholesterol in the red blood cell membrane red blood cells become distorted resulting in the formation of acanthocytes
what can cause hereditary spherocytosis?
Abnormalities or deficiency to: ankyrin, spectrin A or B, Band 3 and Protein 4.2
what can cause hereditary elliptocytosis?
Abnormalities or deficiency to: spectrin A or B, spectrin dimer or spectrin-ankyrin association, as well as Protein 4.1
what is the most abundant haemoglobin in adults?
Alpha 2 Beta 2
what are haemoglobinopathies?
inherited disorders of haemoglobin
what are the two categories of haemoglobinopathies?
thalassemias: reduced synthesis of haemoglobin sickle cell disease: change of one amino acid in the globin for another
what are the two main sources of energy for the red blood cells?
RBC metabolic pathways and the hexose monophosphate shunt
G6PD
glucose 6 phosphate dehydrogenase
G6PD deficiency
NADPH and GSH (glutathione) generation impaired
What can a G6PD deficiency lead to?
acute haemolysis (bleeding)
what is G6PD commonly known as?
enzymopathy
what is the glycotic pathway?
generates energy i the form of ATP that maintains red blood cell shape and deformability
what does disorder of the glycotic pathway cause?
ATP is depleted meaning cells lose large amounts of potassium and water, becoming dehydrated and rigid
chronic non-spheryotic haemolytic anaemia
deficiency of vital enzymes required for glycolysis and red blood cell nucleotide metabolism
microcytes
small red blood cells with less haemoglobin
macrocytes
large red blood cells with more haemoglobin
anisocytosis
presence of red blood cells of unequal size
poikilocytosis
presence of red blood cells of irregular shape
what is the appearance of blood after centrifugation?
bottom: red blood cells middle: white blood cells and platelets top: plasma
describe the nature of red blood cells
biconcave without a nucleus, DNA, RNA or mitochondria
what are red blood cells also known as?
erythrocytes
how does the shape of red blood cells contribute to their function?
allows greater surface area to carry oxygen and squeeze into the narrow lumen of the vascular tissue
what is the lifespan of red blood cells?
120 days
what are white blood cells also known as?
leukocytes
what are the two most common white blood cells?
neutrophils and lymphocytes
describe the nature of neutrophils
polymorphonuclear, granulocyte
polymorphonuclear
irregular, mutli-lobed nucleus
granulocyte
prominent cytoplasmic granules
give two examples of neutrophils
basophil and eosinophil
what is the function of neutrophils?
phagocytose and kill bacteria and fungi
describe the nature of lymphocytes
large, regular nuclei lack granules
what is the function of lymphocytes?
immune response, produces antibodies and kill virus infected cells
what is the role of eosinophils?
kill parasites involved in allergic responses
what is the role of basophils?
kill parasites involved in allergic responses involved in controlling inflammation
what is the role of monocytes?
phagocytosis of dead cells and pathogens
what are platelets also known as?
thrombocytes
describe the nature of platelets
cytoplasmic fragments with no nucleus, membrane bound contain granules that are important for clotting and modulating inflammation
haemostasis
blood clotting
how does blood clot?
fibrinogen (factor 1) is a major plasma protein that is converted to fibrin, forming a blood clot clotting factors control the process and the fibrin clot reinforces primary platelet plug
where do blood cells come from?
mature blood cells are produced from stem cells in the bone marrow
haematopoietic stem cells
immature cells within the bone marrow that can develop into all types of blood cells
give four main components of plasma
water salts proteins organic molecules (metabolites, carbohydrates, lipids)
what is the difference between plasma and serum?
plasma is the fluid component of the blood, minus the clotting factors serum is the fluid remaining after blood has clotted
what percentage of the plasma is protein?
7-9%
what is the main plasma protein?
albumin
what is the role of plasma proteins?
carry substances which are poorly soluble in water such as lipids, hormones and ions
how is plasma involved in the immune response?
immunoglobulins transported which are made by B lymphocytes and act as antibodies against pathogens
complement proteins kill bacteria and other pathogens by cooperating with immunoglobulins and white blood cells
give three functions of blood
transport defence homeostasis
how is blood used for transport?
blood carries oxygen and nutrients to tissues, removing carbon dioxide and waste products
what is the role of red blood cells (erythrocytes)?
transports oxygen from the lungs to tissue and removes carbon dioxide
how is carbon dioxide carried in plasma?
in the form of bicarbonate
what is the role of carbonic anhydrase?
to aid in the transport of carbon dioxide
how does a pulse oximeter work?
measures the colour of haemoglobin and determines if a patient is hypoxic
what is the usual total blood volume for a 70kg male?
~5 litres
what is the usual plasma volume for a 70kg male?
~2.5-3 litres
how do you calculate haematocrit?
volume of cells/total volume
what is the normal haematocrit value?
0.4-0.5
what does a low haematocrit signify?
anaemia and therefore low oxygen
what is a full blood count test?
blood test to determine the number of red blood cells, white blood cells and platelets
how is haemoglobin concentration used?
overall concentration of haemoglobin in the blood- used to diagnose anaemia
what is mean red cell volume?
size of the red blood cells
what is the diameter of a red blood cell?
8 micrometres
what is the thickness of a red blood cell?
2 micrometres
what is mean red cell haemoglobin content?
how much haemoglobin is in each red cell
why is total white blood cell count important?
important for diagnosing infection
what do liver function tests measure?
albumin concentration liver enzymes released from damaged liver cells clotting factors
why do we test for urea and electrolyte levels?
test kidney function metabolic abnormalities
what do we screen for a lipid profile?
triglycerides cholesterol LDL and HDL risk of cardiovascular disease
LDL
low density lipoprotein inflammatory mediator
HDL
high density lipoprotein
Why does blood clot?
Prevents excessive blood loss and pathogens from entering the body and causing infection
Outline primary haemostasis
Endothelium constantly releases VWF, from the Weibel-Palade bodies, into the blood
When damage occurs to the endothelium the subendothelial collagen becomes exposed and any VWF circulating in the blood will bind to it
Platelets carry receptors for VWF and collagen and so are activated- this activation expresses fibrinogen receptors which are necessary for aggregation
Activated platelets can aggregate by binding to fibrinogen, and they release ADP and TXA2
What does primary haemostasis involve?
Platelet aggregation and platelet plug formation
What does secondary haemostasis involve?
Formation of fibrin through conversion by thrombin
Outline secondary haemostasis
When damage occurs to the endothelium, tissue factor is exposed alongisde the subendothelial collagen
Tissue Factor activates the coagulation cascade when FVIIa binds to it, activating FXa
The activation of FXa initiates conversion of prothrombin to thrombin and this causes more platelet aggregation
After the initial trickle of thrombin, FVIIIa and FVa form calcium-ion dependent complexes on the surface of platelets with FXa and FIXa
These complexes increase production of FXa and amplify production of thrombin
Describe fibrinolysis
Tissue plasminogen activator activates plasmin which is converted from plasminogen, and the plasminogen breaks down fibrin into fibrin fragments
Haemophilia
Lack of ability to clot
Thrombophilia
Tendency to develop blood clots in the wrong locations
Disseminated intravascular coagulation
Widespread clotting and obstruction of blood flow to the tissues
Define cardiovascular system
The heart, blood vessels and approximately 5 litres of blood
Functions of the CVS
Transport of oxygen and substrates to cells Transport of carbon dioxide and metabolites from cells through excretion Distribution of hormones Transport of defence mechanisms Thermoregulation
Passive diffusion
Random, unidirected, thermal movement of molecules
How is time proportional to distance in passive diffusion?
Time is directly proportional to the distance squared
Convection transport
Movement of fluids and solutes down a pressure gradient created by the heart
How does the heart have dual circulation?
Pulmonary circulation Systemic circulation
Note
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