Topic 9 - Blood Flashcards
What is an artery?
Brings blood (generally oxygenated) to the heart from the organs and tissues
What is a vein?
Returns blood (generally deoxygenated) from the organs and tissues to the heart
What happens to the blood in one pump of the heart?
- Deoxygenated blood from tissues/organs travels through the Vena Cava into the right atrium.
- Right ventricle pumps the blood through the pulmonary artery to the lungs.
- Valves prevent backflow.
- Reoxygenated blood travels from the lungs to the left atrium through the pulmonary vein.
- Left ventricle pumps blood via the Aorta to the tissues and organs.
What are the functions of the blood?
- Hydration of tissues and organs
- Delivery of oxygen to tissues and organs
- Provision of nutrients to tissues and organs
- Fight infection: innate and adaptive responses
- Regulation of body temperature and pH
- Distribution of endocrine hormones
- Prevent it’s own (blood) loss
Which WBCs contribute to immune response to allergic reactions?
- Eosinophils
- Basophils
What are endocrine hormones?
They are secreted directly to the blood stream.
What are exocrine hormones?
They are secreted through ducts opening on to an epithelium rather than directly into the blood.
How does blood prevent it’s own loss?
- Platelets (small anucleate cells that clump together)
- Blood coagulation pathway (through the formation of thrombin a fibrin clot is formed)
What is the common progenitor cell that all blood cells are derived from?
The multipotential haematopoietic stem cell
What are the two major lineages of blood cells?
- Myeloid
- Lymphoid
Which two blood cells can be found in body tissues?
- Mast cells
- Macrophages
Which 5 blood cells are found in the blood marrow?
- Hemocytoblast (stem cell)
- Common myeloid progenitor
- Megakaryocyte
- Myeloblast
- Common lymphoid progenitor
Which 11 blood cells can be found within blood specifically?
- Platelets
- Basophil
- Neutrophil
- Eosinophil
- Monocyte
- Natural killer cell (large granular lymphocyte)
- Small lymphocyte
- T lymphocyte
- B lymphocyte
- Plasma cell
How can plasma be separated from blood cells?
Centrifugation
What volume of blood is blood plasma?
55%
What are the 3 most abundant blood plasma proteins?
- Albumin
- Immunoglobulins
- Fibrinogen
What is blood serum?
Plasma without the clotting factors
What percentage of blood is taken up by RBC?
45%
What occurs if incompatible blood groups are mixed?
Antibodies in the plasma reacts with antigens on the RBC membrane, causing haemolysis.
Potential complication during blood transfusion/pregnancy.
What is the ABO blood group?
Based on the carbohydrate antigen present on the RBC membrane. A, AB, B and O types.
Which ABO blood type is a universal donor?
O
Which ABO blood type is a universal acceptor?
AB
What are the main symptoms of an acute hemolytic reaction?
- Hypotension
- Kidney failure
- Bleeding
- Chills/Fever
- Hemoglobinuria
What is Hemoglobinuria?
Haemoglobin in the urine due to erythrocyte lysis
What is the Rhesus blood group?
Based on the ion-channel antigen (D-antigen) on the RBC membrane
When does haemolytic disease occur during pregnancy?
Rh- (no D-antigen) woman and a Rh+ fetus (D-antigen).
During birth some foetal blood enters mothers system causing an immune response. In a following pregnancy the immune response will be much larger and will attack the foetus.
How can haemolytic syndrome in a foetus be treated?
Intramuscular injection of mother with Rh antibody at 28 weeks, 34 weeks and within 72 hours after delivery. Intrauterine transfusion via umbilical cord may be necessary.
What are the diseases of blood plasma?
- Bleeding
- Thrombosis
- Hereditary angioedema
- Complement deficiency
What are the diseases of the blood cells?
- Haematological malignancies
- Sickle cell anemia
- Thalassaemia
- Haemoglobinopathies
- Leukopenia
- Thorombocytopenia
- Infectious mononucleosis
What are haemoglobinopaties?
Genetic defect that results in abnormal structure of one of the globin chains of the hemoglobin molecule. eg. Thalassaemia and Sickle cell anemia
What are diseases affecting the platelets called?
Thrombocytopaenias
What is a leukopenia?
A decrease in the number of leukocytes found in the blood, which places individuals at increased risk of infection.
What may cause bleeding?
- Acute injury
- Chronic disease
- Low platelet count
- Coagulation deficiencies
- Vitamin K deficiency
- Drugs
- Liver disease
- Infection/sepsis
- Aneurysm repture
Which drugs can cause bleeding?
- Aspirin
- Warfarin
- Heparin
What is the ultimate killer in heart disease and stroke?
Thrombosis
What are the causes of thrombosis?
- Atherosclerosis
- Cancer
- Immobilisation
- Surgery
- Hypercoagulability
- Thrombocythaemia
- Factor V Leiden
Why does hypercoagulability occur?
Inhibitor deficiencies - PC, PS, AT
What is atherosclerosis?
A disease in which plaque builds up inside your arteries
What is neoplasia?
Uncontrolled cell growth. May be benign/malignant (therefore not necessarily cancer)
Which two classes of genes are implicated in neoplasia?
Tumour suppressor genes
Oncogenes
What are oncogenes?
Genes directly causative of cancer – includes growth factors and their receptors, DNA binding proteins
What are tumour suppressor genes?
Loss of suppressor activity leads to cancer.
What initiates cancer?
- point mutations (UV, radiation, carcinogens)
- chromosome translocation
- viral genes
Which retrovirus is associated with leukemia?
Human T-Lymphotropic Virus (HTLV-1)
What is an example of a cancer caused by chromosomal translocation?
Burkitt’s Lymphoma
How are haemotological malignancies classified?
Blood cell lineage (myeloid neoplasm/lymphoid neoplasm)
Location (leukemia - blood/lymphoma - lymph nodes)
What cells are the precursors of platelets?
Megakaryocytes
What are Myeloproliferative disorders?
A group of slow-growing blood cancers in which the bone marrow makes too many abnormal red blood cells, white blood cells, or platelets, which accumulate in the blood
What are some myeloproliferative disorders?
- Myeloid neoplasia
- Polycythaemia (^ RBC)
- Thrombocythaemia (^ platelets)
- Myelofibrosis (^ megakaryocyte)
- Chronic myeloid leukemia (^ granulocytes)
What does leukemia result in?
Accumulation of WBC in the bone marrow and blood, bone marrow failure.
Decrease in RBC, platelets and eventually WBC themselves in advanced disease.
-blood hyperviscosity
-infection
-tiredness/anemia
-bleeding
-bone pain in children
What is lymphoma?
T or B lymphocyte neoplasia - affecting the lymph nodes
What are the typed of lymphoma?
Non-Hodgkin and Hodgkin
How is Hodgkin lymphoma characterised?
By Reed-Sternberg cells
Where do Reed-Sternberg cells originate?
B lymphocytes, which become enlarged and are multinucleate or have a bilobed nucleus.
What is anemia?
Loss of oxygen delivery
What are the haemoglobin levels in anemia?
<13.5 g/dl (men)
<11.2 g/dl (women)
What are the symptoms of anemia?
- Tiredness
- Pallor
- Fainting
- Tachycardia
- Shortness of breath
What is tachycardia?
A heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults.
What is anemia caused by?
- RBC or haemoglobin production abnormalities
- RBC destruction abnormalities
What are Colony Stimulating Factors involved in?
Haemopoiesis of myeloid cells including RBCs.
What are lymphokines involved in?
Haemopoiesis of lymphocytes and NK cells.
What are two examples of growth factors?
Epo and Thpo
How is Epo produced?
By interstitial fibroblasts in the kidney as an endocrine hormone
What are the causes of an iron deficiency?
- Diet induced
- Blood loss (acute or chronic)
- Infection (hookworm)
- Growth spurts (children), Pregnancy
What is distinctive of RBC in hypochromic microcytic anemia?
- Smaller cells with increased zone of central pallor
- Increased anisocytosis
- Increased poikilocytosis
- Some RBC become elongated
What is anisocytosis?
A medical term meaning that a patient’s red blood cells are of unequal size. This is commonly found in anemia and other blood conditions.
What is poikilocytosis?
Variation in cell shape.
What are Vitamin 12 and Folate involved in?
DNA replication
What does a deficiency in either Vitamin 12 or Folate cause?
- Issues with mitosis of the proerythroblast
- Causing megaloblastic or macrocytic anemia (large RBCs)
What causes Vitamin 12 deficiency?
Reduced absorption
What causes Folate deficiency?
- Poor nutrition
- Alcoholism
- Malabsorption
- Certain drugs (barbiturates, antibiotics and anti-epileptics)
What is a barbiturate?
A drug that acts as a central nervous system depressant, and can therefore produce a wide spectrum of effects, from mild sedation to death.
What does megaloblastic anemia lead to?
- Abnormally large RBCs
- Macroovalocytes
- Hypersegmented Neutrophils
When does chronic blood loss cause anemia?
When the volume of blood lost exceeds the capability for haematopoiesis of bone marrow
What kind of anemia does blood loss lead to?
Normocytic anemia (no RBC abnormalities)
What does growth factor Epo do?
Stimulates haemopoiesis of stem cells into erythrocytes (BFU production) in the bone marrow
What causes haemolytic anemia?
- Increased RBC destruction
- RBC lifespan decreases from 120 to 20 days
- Bone marrow unable to replace sufficient number of RBCs
- Acquired/Inherited
What are the two types of acquired haemolytic anemia?
- Immune
- Non-immune
How is acquired immune haemolytic anemia caused?
- Haemolytic syndrome in newborn (Rh)
- Autoantibodies
- Complement
How is acquired non-immune haemolytic anemia caused?
- Drug-induced
- Snake venom
- Mechanical (heart valves)
- Infections (malaria, septicaemia)
What are the causes of inherited haemolytic anemia? (most haemolytic anemias are inherited)
- RBC cytoskeletal defects (mutations in alpha or bate spectrin)
- RBC enzyme defects (G6PD deficiency in NADPH metabolism)
- Haemoglobin defects (thalassaemia/sickle cell)
What do mutations in alpha or beta spectrin cause?
Hereditary spherocytosis
What is spherocytosis?
The presence in the blood of spherocytes, i.e erythrocytes (red blood cells) that are sphere-shaped rather than bi-concave disk shaped as normal. Spherocytes are found in all hemolytic anemias to some degree.
What is the cause of sickle cell disease?
- Mutation in the Hb beta globin gene (Glu 6 -> Val)
- Polymerisation of Hb, distorting RBCs
What are the effects of sickle cell disease?
- ‘Sickling’ of RBCs
- Sickle cell crisis due to blockage of microvasculature
- Heterozygosity confers protection against malaria
- Increased infection risk
What is a sickle cell crisis?
Pain that can begin suddenly and last several hours to several days. It happens when sickled red blood cells block small blood vessels that carry blood to your bones.
Which haemoblobin genes are found on which chromosomes?
- Two alpha genes on chr 16
- One beta gene on chr 11
What are the main haemoglobins in adults?
- HbA (alpha2beta2)
- HbA2 (alpha2delta2)
- HbF (alpha2gamma2)
What causes alpha thalassaemia?
Generally large deletions of the alpha-globin
What causes beta thalassaemia?
Point mutations in the beta-globin gene
What is haemostasis?
Arrest of blood flow
What is the function of haemostasis?
To prevent severe blood loss after injury
Why is bleeding a significant cause of mortality?
- Trauma
- Aneurysm rupture
- Infection/Drugs
- Haemophilia
What are the main two processes involved in the stemming of bleeding?
- Vasoconstriction (peptides/hormones lead to contraction of smooth muscle cells in the vessel walls)
- Haemostasis (primary and secondary)
What peptides/hormones lead to vasoconstriction?
- Thromboxane
- Serotonin
- Angiotensin
- Vasopressin
What is thromboxane produced by?
Activated platelets
What is serotonin secreted by?
Activated platelets
but produced by enterochromaffin cells, mostly in the GI tract
What is primary haemostasis?
Platelet activation and aggregation
What is secondary haemostasis?
Coagulation pathway activation
What is the precursor or angiotensin?
Angiotensinogen (produced by the liver)
What is the platelet mechanism of haemostasis?
- Primary haemostatic response
- Platelets activated by thrombin & collagen
- Activated platelets change shape
- Activated platelets aggregate to form coagulum
- Platelet response alone is insufficient to stem bleed
What is pseudopodia?
A temporary protrusion of the surface of an amoeboid cell for movement and feeding
What is the coagulation mechanism of haemostasis?
- Secondary haemostasis response
- Involves cascade of proteolytic enzymes in the plasma that activate one another
- Activated by a tissue factor or contact activation
- Produces fibrin clot network
- Coagulation response alone insufficient to stem bleed
What are proteolytic enzymes?
Essential regulators and modulators of the inflammatory response
What categories of coagulation factors are there?
- Serine proteases (enzymes)
- Co-factors
How do coagulation factors usually circulate in the plasma?
As an inactive pro-enzyme
What catalyses the conversion of fibrinogen to fibrin?
Thrombin
Which coagulation factors are serine proteases?
FVIIa FIXa FXa FXIa thrombin trypsin
Which coagulation factors are co-factors?
Tissue factor
FVa
FVIIIa
What is proteolysis?
A protein is cut into smaller fragments, usually by hydrolysis of peptide bonds
How does proteolysis by digestive enzymes differ from proteolysis by coagulation factors?
Digestive: produces many small fragments from many proteins
Coagulation: more specific - one protein, one cut
What is the principle of limited proteolysis and enhancement of trigger?
Small amount of trigger via intermediates leads to a larger amount of product
What are the advantages of a cascading enzymatic pathway?
- Allows for a small trigger to produce a larger amount of product
- Allows foe acceleration of the response
What are some examples of cascading enzymatic pathways?
- Coagulation pathway
- Complement pathway
- Signalling pathways
How is coagulation triggered?
- Exposure of the blood to tissue factor
- TF is transmembrane protein expressed on perivascular cells
- After injury clotting factor FVII from the blood binds to TF expressed on the membranes of perivascular cells
- FVII self activates
- FVIIa proteolytically cleaves and activates FX
- FXa converts prothrombin to thrombin
- Thrombin converts fibrinogen to fibrin
What are perivascular cells?
Situated or occurring around a blood vessel.
What additional reactions to consolidate thrombin generation occur in coagulation?
- Activation of FIX to TF/FVIIa
- FIXa converts FX to FXa
- Activation of FXI, FVIII and FV by thrombin
- FVIIIa and FVa act as co-factors to FIXa and FXa respectivelly
What does a FIX deficiency cause?
Haemophilia B
What does a FVIII deficiency cause?
Haemophilia A
What can the deficiency of FIX/FVIII/FV lead to?
Severe spontaneous bleeding
What can a deficiency of vWF lead to?
Moderate to severe bleeding
What can a deficiency of FXI lead to?
Mild bleeding
Which three pathways can the coagulation system be divided into?
- Extrinsic
- Intrinsic
- Common pathway
What is the extrinsic coagulation pathway triggered by?
TF
What is the intrinsic coagulation pathway triggered by?
Negatively charged surfaces (Silica, polyphosphates released by platelets and misfolded proteins)
Which blood clotting complexes are vitamin K dependent?
TF/FVIIa
FIXa/FVIIIa
FXa/FVa
How do vitamin K dependent clotting factor complexes bind to platelet surface?
Via Ca2+
What is FXIII?
A transglutaminase activated by thrombin that cross-links fibrin to stabilise the fibrin network and increase its resistance to fibrinolysis.
What can a deficiency in FXIII lead to?
- Severe and spontaneous bleeding
- Miscarriage in pregnancy
- Poor wound-healing
How does fibrin help to protect against infection?
Forms fibrin film with fibres behind the film, stops microbes getting in
What is the structure of a platelet?
- Smallest blood cell (2-3 micrometers diameter)
- No nucleus
- Contain alpha-granules and dense granules
- Lifespan 5-9 days
- Produced by megakaryotes
What do alpha granules contain?
- Fibrinogen
- FV
- vWF
- Growth factors
What do dense granules contain?
- ADP/ATP
- Serotonin
- Calcium
- Polyphosphate
How do platelets become activated?
Through signalling through ligand-receptor (eg. collagen) interactions.
Adrenaline activates platelets so that during fight or flight if injured your blood clots.
What is the process of primary haemostasis?
- Resting platelets circulate
- Vascular injury damages endothelium and exposes sub-endothelial collagen
- Platelets bind to collagen via GPVI and alpa-2-beta-1, also vie GPI and vWF. Platelets activate
- Platelets release ADP and thromboxane that further activate them though binding P2Y and TP receptors respectively
- Alpha-llb-beta-3 is activated
- AllbB3 binds fibrinogen and von Willebrand factor, which assist in platelet aggregation and holding the platelet plug together
Which platelet receptor is involved in initial adherence of platelets to collagen?
GPVI/a2b1
Which process is targeted by aspirin?
Thromboxane synthesis
What is spontaneous bleeding?
No obvious cause, but due to coagulopathy, or other disease
What is induced bleeding?
From trauma, surgery
external
What are some examples of internal major bleeding?
- haemophilia (joint/muscle)
- aneurysm rupture
- drug-induced
- gastro-intestinal
What are examples of minor bleeds?
- Normal bruises
- menorhaggia
- epistaxis
