Blood Flashcards
What is blood?
A fluid tissue of the circulatory system
What is the blood composed of?
water
regulated cells
proteins
What is centrifugation?
separates cells from a solution according to size, shape and density
Describe the centrifugation process?
Tube of blood is placed in centrifuge and spun at a high speed
Centrifugal enhanced gravitational forces pull the heavier particles to the bottom of the tube forming a pellet
smaller particles pushed to the top
Describe what is seen when blood is centrifuged?
Three layers seen
1 = PLASMA
pale yellow, ½ of total blood volume, Has serum and clotting proteins, serum is obtained by letting the blood clot before centrifugation
2= OTHER CELLS Middle part(thin layer between plasma and red blood cells)= buffy coat which has other cells such as WBC and platelets
3= RBCs
Bottom layer= red blood cells and haematocrit
How can proteins in blood be used?
Used as a diagnostic tool
if troponin present in blood= out of place should only be in cardiac muscle= cardiac muscle damage= myocardial infarction
What are the 4 main plasma proteins?
haemoglobin
fibrinogen
globulin
albumin
Describe the presence of haemoglobin in blood?
only very small amounts
stored inside RBCs
hidden from plasma leak upon cell damage
How much albumin is present in blood?
35-55g/l
most abundant
Describe the presence of albumin in blood?
Largest contributor to colloid osmotic pressure
Accounts for 22mmHg out of 28mmHg
Ionisable groups that buffer plasma ph
Binds to low molecular weight molecules
Has important carrier for lipophilic molecules with low solubility
Binds to drugs lowering their free conc in plasma
Drugs can compete for binding sites so when 2 drugs administered together that bind to albumin the plasma conc of each of these drugs elevated
How much fibrinogen is present in blood?
28g/l
Describe the presence of fibrinogen in blood?
Haemostasis role
Precursor of blood clots
Small contribution to colloid osmotic pressure
How much globulin is present in blood?
2.3-3.9g/l
Describe the presence of globulin in blood?
high molecular weight globular proteins
water insoluble but dissolve in weak salt solutions like plasma
plasma globulins contribute 6mmHg to colloid osmotic pressure
Immune function= immunoglobulins- antibodies that fight pathogens
Globulin is a broad protein class what does this include?
Transferrin- transports iron, HDL and LDL transport lipids
Clotting factors
Hormones- erythropoietin regulates haematocrit
Carrier proteins
What is the importance of blood tests?
Important information about blood disorders- values outside the range can indicate anaemia
Values compared against normal range
What 3 RBC activity measurements are made in a blood test?
- Haematocrit= RBC : BLOOD VOLUME
- Number of RBC per microlitre of blood
- Average RBC volume= MCV
When are WBC more prominent in circulation?
In case of an infection
What are the most abundant WBCs?
neutrophils
lymphocytes
What types of blood cells have no nuclei?
Platelets/thrombocytes
RBC/erythrocytes
What is the significance of blood cells having no nucleus?
cannot synthesise new proteins
cannot make new protein to repair the damage= loss of their cytoplasmic enzyme activity
retain the enzyme pathways that were made before the nucleus was lost
What are platelets?
Fragments of a large precursor cell
In what process are platelets important?
Homeostasis
Describe the structure and function of a RBC?
Bi-concave shape
Diameter= 7.5um
Thickness=2um
Shape size allows them to squeeze through small capillaries
No organelles= more surface area for haemoglobin carrying
They have glycolytic enzymes= cell metabolism
What are the consequences if a RBC is damaged?
have altered size and shape= can be filtered out of spleen
cells do fit through small capillaries
How are RBCs broke down and fragmented?
by tissue macrophages as part of the reticuloendothelial system=part of the immune system consisting of phagocytic cells
What is Carbonic anhydrase?
An enzyme in RBCs
helps CO2 transportation around body
What reaction does Carbonic anhydrase catalyse?
actalyses carbonic caid production
CO2 + H2O= carbonic acid + protons + bicarbonate ions reaction
What is the role of RBCs/erythrocytes?
package haemoglobin for o2 and co2 transport
What are the 2 types of haemoglobuin and how much of each is present in blood?
- Intracellular haemoglobin= 35g/100ml
- Whole-blood haemoglobin= 15g/100ml= 2x the plasma conc of 7g/100ml
What is the significance of haemoglobin was not encapsulated in RBCs?
would double protein conc in plasma
increase blood viscosity
What process froms new blood cells?
haematopoiesis
What is the life span of a platelet?
10 days
What is the life span of a Leukocyte/WBC?
hours
What is the life span of a erythrocyte/RBC?
120 days
What types of cells are all blood cells derived from?
pluripotent stem cells in bone marrow
What are pluripotent stem cells?
they are master cells that divide and self-replicate and can differentiate into any type of adult cell
What factor causes loss in active haematopoietic marrow?
Age
Upto what age to all bones make blood cells?
5 years
After what age do only sternum vertebrae and pelvis bones make blood cells?
20 years
Describe the step by step process of haemotopoiesis?
- Pluripotent haematopoietic stem cell in one marrow becomes a myeloid or lymphoid progenitor
- Lymphoid progenitor differentiates into lymphoblast then into lymphocytes
- Myeloid progenitor differentiates into megakaryocyte or myeloblast
- Myeloblast(immature blood cell) can differentiate into monocyte, basophil, neutrophil, eosinophil
- Myeloid progenitor can also differentiate into erythrocyte
- Megakaryocyte can fragment with little packets of membrane enclosed cytoplasm = break of = platelets
What controls each step in haemotopoiesis?
haematopoietic growth factor
What are the polymorphonuclear cells?
basophil, eosinophil, neutrophil
What process forms new RBCs?
erythropoiesis
Describe the step by step process of erythropoiesis?
- Myeloid progenitor differentiates into proerythroblast
- This then differentiates into erythroblast(immature erythrocyte)
- Erythroblast differentiates into reticulocytes and whilst doing this loses its nucleus and some organelles
- Up to this point this process is all bone marrow
- Reticulocyte leaves bone marrow and enters blood
- Over the next day loses rest of its organelles
- This becomes a red blood cell
What organ senses the need for more RBCs?
Kidney
How does kidney sense need for more RBCs?
secretes erythropoietin hormone into blood
reaches bone marrow and stimulates erythrocyte production
Increases production rate of erythrocytes by factor of 6 to 8
What is anaemia?
- Blood disorder
-
What are the causes of anaemia?
low haemoglobin conc in blood
Dietary/metabolic deficiency= iron deficiency anaemia
poor vit b12 absorption= pernicious anaemia
Bone marrow aplasia(destruction of bone marrow)- new blood cells cannot be made, caused by alcoholism, drugs, toxins, ionised radiation
Haemorrhage/blood loss due to injury of excessive menstrual bleeding
Ends stage renal disease/kidney disease= cannot produce erythropoietin
Haemolytic anaemia/fragile erythrocytes= hereditary such as-
Sickle cell disease= abnormal haemoglobin= sickle cell shaped RBCs which easily damage and get stuck in capillaries
Thalassemia= reduce haemoglobin production
Spherocytosis- RBC are spherical not bi-concave
What are the consequences of anaemia?
Less effective at carrying oxygen
Reduced haematocrit
What does the shape of RBC indicate about anaemia?
Macrocytic= larger than normal
Microcytic= smaller than normal
What is homeostasis?
Processes that stops blood loss
What 4 events are involved in homeostasis?
- Vasospasm
- Platelet plug formation
- Blood coagulation
- Fibrous tissue formation
Describe the steps during vasospasm?
Injured blood vessel has spasm- reflex constriction of the vessel
Slows down blood flow to injured area to minimise loss
Smooth muscle contraction caused by vasoconstrictors released by damaged tissue and activated platelets e.g. thromboxane A2
Describe the steps during Platelet plug formation?
- Endothelial injury
- Smooth muscle cells detect injury - Collagen exposed
- Platelets adhere to the collagen
- Platelets undergo change in shape= extended filopodia and fully spread= flat and circular with raised bump in the middle
- Release reaction
- This change in shape causes degranulation
- Release of chemical mediators attracts other platelets to site of injury- ADP, TXA2, serotonin, adrenaline, calcium
- These are needed for coagulation cascade
- ADP helps platelets adhere to endothelium - GPIIb/IIIa is expressed
- GPIIb/IIIa causes fibrinogen binding leading to aggregation and linking of platelets
- This then forms a platelet plug
Describe briefly what is involved in Blood coagulation?
Cascade of enzyme reactions
Blood coagulates when enzyme cascade causes fibrinogen to polymerise into fibrin and form fibrin mesh network
Net traps platelets blood cells and other molecules which holds them to the injured site blocking the gap and stopping blood leaking
Describe the steps during Fibrous tissue formation?
Damaged area cells synthesise into collagen fibres
form fibrous connective tissue around injured area and heal it
Yellow structures= fibrin network
Red= erythrocytes
Platelets= blue/grey
Describe in detail the steps involved in Blood coagulation?
- Vessel damage generates prothrombin activators
Enzymes are inert and in circulating blood
Activated by intrinsic and extrinsic pathways - Prothrombin activators convert prothrombin to thrombin
- Thrombin’s effects
Conversion of fibrinogen into fibrin
Stimulates prothrombin activation to provide positive feedback which amplifies thrombin production
Promotes cross-linking of fibrin strands for stronger clot
What are purposes of the intrinsic and extrinsic pathways in blood coagulation?
generates prothrombin activators
coagulation cascade pathways
Describe the steps in Intrinsic pathway?
- Factor XII circulating
- Has surface contact with platelets
- Then becomes factor XIIa
- This then cleaves F XI into F XIa
- F XIa and calcium ions cleave IX to IXa
- IXa and VIIIa and calcium enter common pathway
Describe the steps in Extrinsic pathway?
- Tissue damage
- Exposure of endothelial layer cells
- Tissue factor is embedded in membrane
- VII binds to tissue factor and becomes VIIa
- VIIa and calcium also enter common pathway
Describe the steps in common pathway?
Both intrinsic and extrinsic have produced factor X
Common pathway
- Factor X cleaved to Xa
- XA cleaves V into Va
- Xa + Va + Ca cause factor II/prothrombin to be cleaved to F IIa(thrombin)
- Thrombin does 3 things
1. Thrombin activates platelets
2. Thrombin activates stabilising factor XIIIa by cleaving XII, XIIIa along with calcium stabilise the crosslinked fibrin polymer when fibrinogen is converted to fibrin
3. Thrombin causes platelet aggregation and causes platelet GPIIb/IIIa expression
Why are there so many coagulation factors and steps?
Clotting needs to happen quickly to stop blood loss
factors promote and prevent coagulation= Achieve the balance
What are the mechanisms that promote efficient clotting?
- Amplification= at each step of the coagulation cascade, enzyme activation by 1 molecule= multiple products formed
- Amplification multiplied at each step= the product of each reaction is a catalytic activator of the next step
- Positive feedback= thrombin acts back on earlier step to produce more thrombin
- Stimulation of cross linking of fibrin into the network by thrombin forms stable clot
What are the mechanisms that prevent harmful clotting?
- Diluting of clotting factors= by the constant blood flow through circulation
- Tissue macrophage system= Kupffer liver cells(phagocytic cell that forms the lining of the sinusoids of the liver and breaks down red blood cells) remove activated factors from circulation
- Circulation of antithrombin(protease inhibitor)= prevents thrombin being activated by inactivating upstream factors
- Generation of neutralising factors by endothelial cells
Prostacyclin and nitric oxide= inhibit platelet activation
Tissue factor pathway inhibitor= blocks extrinsic pathway by binding to tissue factor-factor VIIa complex
Thrombomodulin= protein on endothelial surface converts thrombin to an anticoagulant enzyme
Heparin= anticoagulant which binds and activates antithrombin
What dietary components are needed for RBC production?
- Iron for haemoglobin
- Vitamin b12 for DNA synthesis, fatty acid metabolism, amino acid metabolism
- Folic acid for DNA synthesis
What percentage of the blood is composed of plasma?
~55%
What can stimulate erythropoietin secretion?
Low O2 blood levels
Where is erythropoietin produced?
Kidneys
