Blood Flashcards
What does blood consist of?
Label what cells you can see on a normal blood film
Red cells = predominant. Purple looking cells= white cells. Red dots which appear much smaller= platelets
Describe and explain red blood cells
RBCs/erythrocytes are biconcave discs. No nucleus, mitochondria and ER.
Narrow in the centre to be able to deform & pass through 3 micron capillaries sin fragmentation.
Diameter = ~8 micro m. Thickness= ~2 micro m
What is the red blood cell membrane made of?
Red cell membrane consists of: proteins, lipids and carbs in a semi-permeable lipid bilayer. Hay
An outer hydrophilic portion composed of glycolipids, glycoproteins, and proteins.
A central hydrophobic layer w proteins, cholesterol, and phospholipids
An inner hydrophilic layer of mesh-like cytoskeletal proteins to support lipid bilayer.
The lipid component of the RBC membrane includes…
How are the lipid components arranged in the cell membrane?
…Phospholipids, Cholesterol, Sphingolipids
Phospholipids are distributed asymmetrically. Hay free cholesterol between the bilayer to ⇡ membrane fluidity
The outer phospholipids are Phosphatidyl choline and Sphingomyelin. These are uncharged. Sphingolipids regulate the formation of lipid rafts for cell signalling
The inner phospholipids are charged ( Phosphatidyl ethanolamine and Phosphatidyl serine)
What are integral membrane proteins for RBCs?
Integral membrane proteins: Extend from outer surface and traverse entire lipid bilayer membrane to inner surface
2 major integral membrane proteins are glycophorins: A, B, and C, and band 3: anion transporter
Other integral proteins are: Na+/K+ ATPase, Aquaporin 1, surface receptors, e.g. TfR
What are peripheral proteins in the RBC membrane?
Peripheral proteins are imited to cytoplasmic surface of the membrane and forms the RBC cytoskeleton.
The cytoskeleton acts as tough framework to support the bilayer, it’s responsible for deformability & maintains biconcave shape.
Major peripheral proteins: Spectrin, Ankyrin, Protein 4.1 and Actin
Describe and explain spectrin
Spectrin is the most abundant peripheral protein. Composed of alpha & beta chains
V important in RBC membrane integrity bc it binds w other peripheral proteins to form the cytoskeletal network of microfilaments.
It controls biconcave shape and deformability of cell. If denatured RBC becomes spherical, loses flexibility
Explain ankyrin, protein 4.1 and actin in the rbc membrane
Ankyrin: primarily anchors lipid bilayer to membrane skeleton by interacting w spectrin and Band 3
Protein 4.1: may link the cytoskeleton to the membrane by associating w glycophorin. It also stabilises interaction of spectrin w actin
Actin:contracts/relaxes the membrane. Strong cohesion between bilayer and membrane skeleton maintains SA.
Explain the carbohydrates found in RBC membranes
They occur only on the external surface of cell.
The carbohydrate groups are attached to proteins and lipids by process called glycosylation.
Can contain 2-60 monosaccharide units, either branched or straight.
The carbohydrate gives a cell identity; the distinguishing factor for human blood types.
Which monosaccarides are found on the red cell membrane?
What are blood group antigens?
Blood group antigens on RBC membrane determine our blood group.
Many antigens are proteins: e.g. Rhesus, Duffy, Kidd. Others are carbohydrates; e.g. ABO. Others are combo of glycolipids and proteins.
What is the primary function of the RBC? How is it adapted to its function?
Primary function of RBC is transport of resp gases to and from the tissues.
Its deformability and elasticity allows passage through capillaries. They travel the microvascular system sin mechanical or shape damage, which facilitates gas exch.
The RBCM is tough yet highly flexible- Cytoskeletal proteins interact w the membrane lipid bilayer for strength and flexibility.
The biconcave shape provides optimum SA:V ratio for resp exchange
What does an increase in free plasma cholesterol signify?
What does increased cholesterol lead to? Draw these
Membrane cholesterol exists in eqm w plasma cholesterol. So, ⇡ in free plasma cholesterol causes accumulation of cholesterol in the RBCM
RBCs with increased cholesterol appear distorted and form acanthocytes.
Increase in cholesterol and phospholipid is a cause of target cells. These are RBCs that look like a target.
Target cells appear when the surface of the red cell ⇡ disproportionately to its volume. Can be due to a decrease in Hb or an increase in cell membrane.
Explain Hereditary Spherocytosis
Caused by mutations in membrane protein genes that allow for the erythrocytes to change shape.
Eg you can have deficiency or abnormalities for: Ankyrin, A or B spectrin, Band 3 protein, Protein 4.2.
Erythrocytes get sphere-shaped (spherocytosis), not biconcave. Dysfunctional membrane proteins limit the cell’s flexiblity to travel from arteries to capillaries. Shape change also makes the RBCs more prone to rupture.
Hereditary Elliptocytosis?
Genetic disorder which causes anaemia symptoms, cells become more elliptical. Can be caused by:
A or B spectrin mutation – defective spectrin dimer
A or B spectrin mutation – defective spectrin-ankyrin association
Protein 4.1 deficiency or abnormalities
Explain the following terms: Anisocytosis, poikilocytosis, macrocytes, microcytes.
Anisocytosis= hay mas RBCs of varying sizes on your blood smear.
Poikilocytosis= Hay RBCs of varying shapes on your blood smear.
Macrocytes are larger than normal red blood cells, microcytes are smaller than normal red blood cells.
Causes: anemias, hereditary spherocytosis/elliptocytosis, thalassemia etc
What features allow RBC to withstand life without structural deterioration?
Geometry of cell; SA:V ratio facilitates deformation whilst maintaining constant SA.
Membrane deformability: spectrins undergo reversible change in conformation: some uncoiled and extend, others compress and fold.
Cytoplasmic viscosity determined by MCHC (mean cell Hb content). As MCHC rises, viscosity rises exponentially.
Explain haemoglobin’s structure.
Haemoglobin (Hb) is a globular haemoprotein. Haemoproteins are group of specialized proteins that contain haem as a tightly bound prosthetic group.
Haem is a complex of protoporphyrin IX and ferrous (Fe2+). Fe2+ is bonded to the 4 nitrogen of a porphyrin ring.
Globin: 4 polypep subunits, 2 α-globin chains and 2 β-globin chains
Haemoglobinopathies?
Haemoglobinopathies are a group of recessively inherited genetic conditions affecting Hb
Hay 2 categories: Thalassaemias and Sickle Cell Disease
Describe and explain the red cell enzymes.
2 main enzymes: G-6-P dehydrogenase (G-6-PD) and Pyruvate Kinase (PK). These support pentose phosphate and Glycolysis pathways
The pathways provide energy required for: Maintenance of cation pumps, maintenance of RBC integrity and deformability, maintenance of Hb in reduced state
Methaemoglobin reductase maintains iron in ferrous state
Describe neutrophils
They are bigger than RBCs and are polymorphonuclear, meaning tienen an irregular, multi lobed nucleus.
It is a granulocyte, so contains prominent cytoplasmic granules. They phagocytose and kill bacteria and fungi.
Are the main mediators of innate immunity.
What can granulocytes refer to?
Granulocyte describes neutrophils but it can also refer to:
Eosinophils, where the granules stain red w eosin. 1-4% of wbcs. Used in allergic reactions and kills parasites
Basinophils, where granules stain blue/purple w basic dyes. <0.5%. Involved in defence against bacteria, kill parasites, involved in inflammation
What are mononuclear cells?
Mononuclear cells lack granules, with large regular nuclei. Hay:
monocytes involved in phagocytosis, and lymphocytes involved in antibody production, generally for viruses.
Describe platelets
A.k.a. thrombocytes. They’re cytoplasmic fragments, no nucleus, membrane-bound.
Primary Haemostasis forms a platelet plug. This stops bleeding but it’s insecure and temporary. Fibrinogen is a major plasma protein, converted to fibrin⇢ clot
Describe plasma.
Plasma is fluid containing water, salt, proteins, organic molecules (metabolites carbs lipids, hormones, clotting factors and metal ions)
Plasma is the fluid component of whole blood. Serum is the fluid left after blood clotting. 7-9% of plasma is protein, mostly albumin. Plasma proteins carry poorly-water-soluble substances like lipids.
Plasma maintains pH, ion concentration and protein concentration so it is involved in homeostasis.
What is the haematocrit (Ht) value?
AKA packed cell volume (PCV). It is the volume of cells/ the total volume. Normal value= ~0.4-0.5
describe and explain a FBC
Full blood count (FBC): includes Hb conc (Hb in g/l), which is the overall Hb conc in the blood. This diagnoses anaemia
Mean (red) cell volume (MCV)= size of the rbcs
Mean cell haemoglobin content (MCHC)= how much Hb in each red cell
Haematocrit (Ht or Hc)
Total wbc count, neutrophil count, lymphocyte count
These help diagnose the type of anaemia or infection for WBCs
Describe an LFT
Describe and explain the remaining blood tests.
outline primary haemostasis
Primary and secondary steps are intertwined at many points.
The endothelium continuously releases von Willebrand Factor which circulates in the blood. Endothelial cells also store vWF in Weibel-Palade bodies.
When the endothelium is damaged and exposes collagen, von Willebrand Factor binds to collagen.
Platelets express receptors for collagen and vWF, becoming activated when these proteins bind to them. Platelets change shape.
Platelets also release multiple pro-activation/ aggregation signalling molecules like ADP and thromboxane A2 (TXA2). This activates other platelets that haven’t bound to vwf (positive feedback).
Activated platelets express fibrinogen receptors. Platelets aggregate by binding to fibrinogen, which links platelets juntos.
Outline secondary haemostasis
In secondary haemostasis, tissue factor (TF) on sub-endothelial cells activates the coagulation cascade.
TF becomes exposed and released. Upon exposure to TF, FVIIa binds to it. This will lead to activation of FXa which converts prothrombin to thrombin.
Thrombin activates platelets and releases further cytokines from platelets. It can also release further VWF from endothelial cells, amplifying platelet aggregation.
Thrombin activates 2 cofactors, FVIIIa and FVa. These form Ca2+ dependent complexes on platelet surfaces w Factor Xa (aka prothrombinase complex) and Factor IXa (aka tenase complex).
These complexes accelerate production of Factor Xa and thus thrombin production. This= amplification of coagulation cascade.
What is fibrinolysis?
Breaking down fibrin mesh. tPA is expressed on the surface of endothelial cells. This is released and activates plasmin from plasminogen. Plasmin breaks down fibrin
Explain how thrombin participates in wound healing
The thrombin produced as part of secondary haemostasis is used to convert soluble fibrinogen into insoluble fibrin mesh, which traps platelets, seals the wound and contributes to wound healing
What is haemophillia?
Haemophilia - failing to clot, due to mutations in coagulation factors.
Hay haemophillia A and B
Haemophillia A can cause massive haemorrhage and swelling
what is thrombosis?
Thrombosis= clotting in the wrong place
Arterial= clot in the artery due to atherosclerosis (eg stroke)
Venous (e.g. DVT)= a blood clot in a vein, usually the leg. Causes swelling and colour changes
What is DIC?
Disseminated intravascular coagulation (DIC) – whole body clots
As in sepsis; body’s response to an infection injures its own tissues/organs. Small blood clots form throughout the bloodstream, blocking small blood vessels.
The increased clotting depletes the platelets and clotting factors needed to control bleeding, causing excessive bleeding.
Describe the role of the clotting system in defence
Coagulation proteins are needed to eradicate invading pathogens- TF also activates protease activated receptors (PARs) on immune cells.
PAR-dependent signals evoke pro- and anti-inflammatory pathways that regulate migration and proliferation of immune cells.
Containment hypothesis: coagulation activation forms a physical barrier. This facilitates pathogen clearance by immune cells
Draw a diagram of the haemostatic pathway. Show where cells and their surfaces are crucial to the pathway
An Exercising student lifts heavy weights – their BP increases to 160/95 mmHg from a resting value of 118/83 mmHg, why?
Muscles need more O2.
The student increases blood flow by increasing CO through increasing HR and SV.
Their heart works faster + with stronger contraction, increasing BP
What mechanisms do we have in place to control blood pressure?
Hay mechanisms which control blood pressure by modulating HR, SV and TPR
To increase low BP: Sympathetic Nervous System, Renin-Angiotensin-Aldosterone System (RAAS), Anti-diuretic hormone (ADH or Vasopressin)
To reduce raised BP: Cardiac Natriuretic Peptides
How does the symp ns affect bp?
The symp ns releases NA, adrenaline and stimulates the RAAS system. These increase HR, SV and TPR
What is the RAAS system and how does it affect blood pa?
The symp ns and decrease in blood pa/blood flow to the kidneys triggers increase in renin release.
This causes conversion of angiotensin to angiotensin I. Ang I goes into the lungs. Using angiotensin converting enzyme (ACE) Ang I is converted to Ang II. Ang acts at AT1 receptors on blood vessels and adrenal glands
On blood vessels this ⇡ vasoconstriction which ⇡ TPR. It also acts on adrenal glands and releases aldosterone. This ⇡ Na/ H2O reabsorption which ⇡ SV
What is the role of ADH /vasopressin on blood pressure?
ADH is produced by neurones in hypothalamus.
Its released from terminals into posterior lobe of pituitary gland and excreted into the bloodstream
Secretion of ADH stimulated by decrease in blood volume associated w decrease in BP. This is sensed by cardiac pa receptors in left atrium which send signals to hypothalamus.
ADH directly acts on blood vessels to increase vasoconstriction which increases TPR.
It also inserts aquaporin channels in the kidneys which retain more water. This increases blood volume/sv
How do Cardiac Natriuretic Peptides control blood pressure?
Atrial and Brain Natriuretic Peptides (ANP/BNP) are released from specialised cells in atria.
Increased cardiac filling pressures due to high BP leads to ⇡ ANP/BNP secretion.
In the kidney it increases excretion of Na/H2O, which lowers Blood volume, SV and therefore BP
In blood vessels hay vasodilatation, ⇣ TPR and bp
Increased plasma ANP/BNP levels indicate heart failure. Its release is an attempt to reduce congestion (volume overload)
