Haematology 1 Flashcards
What are the functions of the blood?
Delivers nutrients to tissues
Removal of waste materials
Communication route
Suspensions of cellular elements- allows biochemical tests to be carried out.
What is transported in the blood?
Oxygen
Carbon dioxide
Nutrients
Hormones
Heat
Waste products
What is regulated in the blood?
Homeostasis of:
Body fluids
pH
Temperature
Cell water content
What does the blood protect against?
Excessive loss by clotting
Infections (WBC)
What are the blood components?
Cells (RBC, WBC, platelets) and soluble factors (water, proteins, gases and nutrients)
Plasma- WBC and platelets
Serum- allows the clot to form, efficiently removes RBC
Another name for red blood cells
erythrocytes
Another name for white blood cells
leukocytes
Lymphocytes are a type of leukocyte
Another name for platelets
thrombocytes
Another name for factor
protein
How long do lymphocytes last?
Long-lived and last for years
How long do most other blood cells last?
Hours/days/weeks
What is the RBC and platelet number like?
It remains relatively stable
What is the WBC count like?
It varies depending on invading pathogens/foreign antigens
Another name for blood cell production
haematopoiesis
What are pluripotent stem cells?
They differentiate into blood cell types
What is erythropoiesis?
The production of red blood cells
Where do red blood cells originate from?
The myeloid stem cell
Same as granulocytes, monocytes, mast cells (MC), megakaryocytes
What ejects the nucleus to form reticulocyte? (immature RBC)
Proerythrocyte
Name some features of the RBC
Anuclear with no other organelles
binconcave discs
Contains the protein haemoglobin (Hb)- which carries oxygen to all the cells and some carbon dioxide to the lungs.
What is included in a Hb molecule?
4 haem groups with a iron (Fe 2+) ion
Allows binding of the 4 x O2
What factor increases the oxygen transport efficiency?
Lack of nucleus and organelles
Where does erythropoiesis occur?
In the bone marrow (BM) red pulp
How long do RBCs live for?
Approximately 120 days
How are the dead cells removed from circulation?
By the spleen and the liver
What happens to the breakdown products?
They are recycled and reused
What is the process of erythropoiesis?
Low oxygen concentration is sensed by the kidneys which release erythropoietin (EPO).
This then stimulates differentiation of HSC to RBC
Reticulocytes (immature RBC) enter circulation and mature in 1-2 days
Homeostasis with the blood oxygen
All blood cells are derived from which cell type?
- Common lymphoid precursor
- Common myeloid precursor
- Haematopoietic stem cell
- Neural stem cell progenitor
- Promonocyte
Answer: 3
How many oxygen molecules can bind to two haemoglobin molecules?
- 2
- 4
- 6
- 7
- 8
Answer: 5
What word refers to the production of red blood cells?
- Angiogenesis
- Erythropoiesis
- Haemostasis
- Haematopoiesis
- Homeostasis
Answer: 2
What do WBCs (leukocytes) contain?
A nucleus and organelles but no Hb
What does granular mean and give examples
Granular- contains vesicles (‘granules’ can be stained)
e.g. neutrophils, eosinophils, basophils
What does Agranular mean and give examples
Does not contain granules
e.g. lymphocytes, monocytes
How long do WBCs last and what is their function?
May live for several months/years
Function- to combat invading microbes.
Where do the WBCs go during infection?
WBCs leave bloodstream during infection and collect at sites (tissues) of invasion- diapedesis (extravasation)
Features of WBC: neutrophils
Majority of WBC (70%) and granulocytes (90%)
Short-lived (0.5-3 days)
Granular cytoplasm with multilobular nucleus
Accumulates rapidly at sites of infection/injury
- Phagacytose
- Secrete enzymes
Features of WBC: eosinophils
Moderately short-lived (5-12 days)
Most abundant in small intestine
Prominent cytoplasmic granules for immune response to helminths and parasites
Degranulation- release of granule contents into extracellular space
Features of WBC: basophils
Found in low numbers in the blood, similar to mast cells
Roles in allergy (type I hypersensitivity) and autoimmune disorders
Granules contain heparin (anticoagulant), cytokines and lipid mediators
Features of WBC: lymphocytes
B cells and T cells (with many subtypes).
Derived from lymphoid precursor
Mediate the innate and adaptive immune response
1. Plasma B cells secrete antibodies
2. Memory B cells speed up subsequent response to infection
3. Cytotoxic T cells induce cell death of infected/ cancerous cells
Features of WBC: monocytes
Agranular myloid cell in the bloodstream
Mobilised to inflammatory sites after neutrophils
Differentiate into tissue-resident macrophages
How are platelets produced?
By splintering of megakaryocytes (Mk) in red bone marrow into 2000-3000 fragments
What hormone controls the HSC differentiation into Mk and platelets?
Thrombopoietin
Features of platelets
Contains many vesicles but no nucleus
Platelets facilitate blood clotting
Can survive for 5-9 days
What is the RBC count for both females and males?
Females- 4.8 x 10 ^6 /microliter
Males- 5.4 x 10 ^6 /microliter
What is the platelets count?
1.5- 4 x 10 ^5 /microliter
What is the WBC count?
5-10 x 10 ^3 /microliter
What is the WBC count (%) for each individual one?
Neutrophil- 60-70%
Eosinophil- 2-4%
Basophil- 0.5-1%
Lymphocyte- 20-25%
Monocyte- 3-8%
Which short-lived granulocyte is considered a ‘first-line responder’ and is rapidly recruited to sites of inflammation and injury?
- Basophil
- Eosinophil
- Erythrocyte
- Macrophage
- Monocyte
- Neutrophil
Answer: 6
Which of these myeloid cells is not typically tissue-resident?
- Alveolar macrophage
- Hofbauer cell
- Langerhans cell
- Microglia
- Monocyte
Answer: 5
Which of the following is anuclear?
- Basophil
- Macrophage
- Megakaryocyte
- Monocyte
- Neutrophil
- Platelet
Answer: 6
What is the sequence of responses that stop bleeding?
- Vascular constriction
- Platelet plug formation
- Blood clotting (coagulation)
What factors are involved in clotting?
Coagulation factors
Name 2 ways it can be activated?
Extrinsic pathway
Intrinsic pathway
Where does it converge on?
Prothrombinase formation, which leads to the common pathway.
What could a rupture in the endothelial lining lead to?
Blood loss
What do the smooth muscle do to prevent this from happening?
The smooth muscle surrounding the endothelium constricts
What happens to damaged endothelium?
It secretes endothelin which binds to receptors on smooth muscle cells, initiating constriction
What are the different functions of platelets?
- Homeostasis
- Inflammation
- Antimicrobial activity
- Angiogenesis
- Tumor growth and metastasis
Names of several family of receptors?
- Integrins
- Prostaglandin receptors
- Lipid receptors
- Transmembrane receptors
- Tyrosine kinase receptors
- Selectins
- Immunoglobin superfamily receptors
What is the process of platelet activation and plug formation?
- Activation of surface receptors increases platelet
[Ca 2+] - Platelet conformational (shape) change to spiny spherical shape (extended pseudopodia)
- Activated platelets release granule contents (ADP, serotonin, fibronectin, von Willebrand factor; vWF)
What are the remaining stages to platelet activation and plug formation?
- Increased platelet [Ca 2+] also stimulates membrane phospholipase A2 activity
- Phospholipase A2 liberates arachidonic acid from membrane phospholipids
- Arachidonic acid is converted to prostaglandin H2 (PGH2) by cyclooxygenase 1 (COX-1)
- PGH2 id further metabolised to thromboxane A2 (TXA2) by thromboxane synthase
What is the function of vWF?
Promotes platelet adhesion to exposed collagen (temporary plug formation)
What is the function of ADP?
Stimulates platelet aggregation
What is the function of serotonin (5HT) and TXA2?
Induces smooth muscle contraction and platelet aggregation
Features of von Willebrand factor (vWF)
Is a multimeric glycoprotein
Made of identical subunits that contain binding sites for both platelet glycoprotein receptors and collagen
- Many different functional domains
- High molecular weight multimers (HMWM) support this binding
Is the initial haemostatic platelet plug stable?
It is not stable and would be washed away by circulation
What do two of the converging pathways act to produce via activation of a cascade of coagulation factors?
Thrombin
- Extrinsic- quick; intrinsic- slow
What is thrombin and its function?
It is an enzyme that converts soluble plasma fibrinogen into insoluble, cross-linked fibrin
What are the components like in circulation?
They are normally inert
What initiates a cascade of events?
Interacting with signalling agents
Examples of a signalling event
pathogen, damage
A rupture of a blood vessel exposes what?
A glycoprotein called tissue factor (TF)
What does tissue factor bind to?
TF binds factor VII (readily present in the blood) to form a dimer protein complex- TF-VII
What is serine protease and what does it do?
TF-VII is a serine protease and it activates factor X to factor Xa as well as factor IX to IXa
What is the function of IXA?
IXA also activates factor X to factor Xa- amplifying mechanism
Coagulation-intrinsic pathway
Ruptured blood vessels expose what?
Prekallikrein (PK) and high molecular weight kininogen (HMWK) which complex and activate factor XIIa
Which actives which factor?
- XIIa activates factor XI into XIa
- XIa* activates factor IX into Ixa
- IXa activates factor X into Xa
What factor does it begin with and what does it form?
Begins with factor X (produced in the liver) which is activated to form factor Xa
Xa forms a dimer with factor Va to form prothrombinase
Prothrombinase converts prothrombin (II) to thrombin (IIa)
Thrombin (serine protease) converts what to what?
Converts fibrinogen into insoluble fibrin, which cross-links and stabilises clot
Features of coagulation with thrombin
- Amplication- positive feedback loop
- Polymerised fibrin is held together by non-covalent and electrostatic forces
What is required for normal clot formation?
Vitamin K- synthesis of 4 clotting factors
What helps dissolve small, unwanted clots?
Plasmin- fibrinolytic system
Natural coagulants- features of Tissue-factor pathway inhibitor (TFP1)
Produced by epithelial cells ; inhibits TF
Features of antithrombin
Inhibits IIa, xa, IXa, XIa, XIIa
Features of thrombomodulin
Released by endothelium, converts thrombin to inactive form
Features of prostacyclin I2 (PGI2)
Released by endothelium, inhibits platelet activation (1 degree homeostasis)
Features of protein C
Activated by thrombin; inhibits V and VIII
Pharmacological anticoagulants- warfarin and its features
In the form of tablets, formation of vitamin-dependent clotting factors
e.g. II, VII, IX, X
Heparin and its features
Occurs naturally in the blood, but also a drug (injection or i.v. drip)
Activates antithrombin III to inactivate thrombin, prevents formation of fibrin/clot
Clotting factor deficiencies- low concentration of clotting factor proteins- disseminated intravascular coagulation
Overactive clotting obstructs:
- small vessels
- depletes platelets and factors
- Causes excessive bleeding
Vitamin K deficiency
Impaired activation of zymogen factors II (thrombin), VII, IX, and X causing impaired clotting
Liver disease
Impaired liver function- impaired production of clotting factors by liver parenchymal cells
Overdevelopment of circulating anticoagulants
Decreased clotting, similar symptoms to haemophilia
Features of haemophilia
Impaired blood clotting due to lack of clotting factors:
- low concentration of either VIII or IX
How is haemophilia caused?
Caused by genetic mutations in one of the genes coding for these factors.
- Haemophilia A- VIII mutation and deficiency
- Haemophilia B- IX mutation and deficiency
What are the symptoms of haemophilia?
Prolonged bleeding, internal bleeding (joint pain, bruising), small increased risk of brain haemorrhage
What type of genetic mutation is haemophilia?
X-linked recessive gene mutation- affected father, unaffected mother, unaffected son, carrier daughter, unaffected son and carrier daughter
What is von Willebrand disease (vWD)
A genetic defect in vWF (platelet adhesion)
vWF is a glycoprotein that helps form a platelet plug
What are the 4 types of vWD?
Type 1- most common, reduced [vWF], only a problem following surgery
Type 2- abnormal vWF function- more frequency bleeding
Type 3- most severe and rare- extremely low [vWF]
Acquired- non-genetic, usually associated with blood, immunological, or heart problems
Mechanical tissue disruption activates the extrinsic coagulation cascade through exposure of which glycoprotein?
- Factor IIa
- Factor XI
- Fibrin
- Fibrinogen
- Tissue factor
- Von Willebrand factor
Answer: 5
Which serine protease catalyses the production of thrombin from prothrombin?
- Antithrombin
- TF-VII complex
- Plasmin
- Prothrombinase
- Protein C
Answer: 4
Which of the following is a non-genetic coagulation disorder?
- Acquired vWD
- Haemophilia type A
- Haemophilia type B
- Type 1 vWD
- Type 2 vWD
- Type 3 vWD
Answer: 1
