CVS T

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

1. sodium/potassium ATPase
2. Aquaporin 1
3. 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

1. actin
2. spectrin
3. ankyrin
4. 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?

1. immunoglobulins transported which are made by B lymphocytes and act as antibodies against pathogens
2. 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

1. Endothelium constantly releases VWF, from the Weibel-Palade bodies, into the blood
2. When damage occurs to the endothelium the subendothelial collagen becomes exposed and any VWF circulating in the blood will bind to it
3. Platelets carry receptors for VWF and collagen and so are activated- this activation expresses fibrinogen receptors which are necessary for aggregation
4. 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

1. When damage occurs to the endothelium, tissue factor is exposed alongisde the subendothelial collagen
2. Tissue Factor activates the coagulation cascade when FVIIa binds to it, activating FXa
3. The activation of FXa initiates conversion of prothrombin to thrombin and this causes more platelet aggregation
4. After the initial trickle of thrombin, FVIIIa and FVa form calcium-ion dependent complexes on the surface of platelets with FXa and FIXa
5. 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