Haemotology Flashcards

1
Q

What is haemotology

A

The study of the normal and pathological aspects of blood and blood elements.

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2
Q

What do haematologists do?

A

Haematologists diagnose, treat and care for patients with a range of disorders affecting blood including:

Bleeding disorders
Haematological malignancies
Haemoglobinopathies
Blood transfusion
Bone marrow and stem cell transplantation

Over 130 million haematology tests are performed in England every year.

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3
Q

How much volume of blood in a man?

A

A volume of approximately 5 ½ litres in a 70kg man (8% of body weight)

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4
Q

Blood physical characteristics

A

Physical characteristics:

Sticky, opaque fluid with metallic taste
Colour varies with O2 content High O2 - scarlet; low O2 - dark red
pH 7.35–7.45

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5
Q

Blood viscosity

A

Whole blood is about 4.5-5.5 times as viscous as water, indicating that it is more resistant to flow than water. Thisviscosityis vital to the function of blood because if blood flows too easily or with too much resistance, it can strain the heart and lead to severe cardiovascular problems.

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6
Q

Blood in females

A

Females have around 4-5 litres, while males have around 5-6 litres. This difference is mainly due to the differences in body size between men and women.

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7
Q

Functions of blood

A

Transport

Delivering O2 and nutrients to body cells

Transporting metabolic wastes to lungs and kidneys for elimination

Transporting hormones from endocrine organs to target organs

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8
Q

2) Function of blood

A

Regulation

Maintaining body temperature by absorbing and distributing heat

Maintaining normal pH using buffers; alkaline reserve of bicarbonate ions

Maintaining adequate fluid volume in circulatory system

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9
Q

3) Function of blood

A

Protection

Prevents excess blood loss following injury
- Platelets
- Plasma proteins

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10
Q

4) Function of blood

A

Prevents Infection
- White blood cells (leukocytes)
- Antibodies
- Complement proteins

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11
Q

Blood composition?

A

1) Withdraw blood
and place in tube.
2) Centrifuge

  • Plasma 55% of whole blood
    Least dense component
  • Buffy coat
    <1% of whole blood contains the leukocytes and platelets
  • Erythrocytes
    45% of whole blood (haematocrit). Most dense component
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12
Q

Red cells abundancy

A

Red cells most abundant
Adult male - 4.50 - 6.50 x 1012/L
Adult female – 3.80 – 5.80 x 1012/L

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13
Q

What are Leukocytes and functions

A
  • Make up <1% of total blood volume
  • 4^– 11 x 109 /L of blood

Function: in defence against disease
Can leave capillaries via diapedesis
Move through tissue spaces by ameboid motion and positive chemotaxis

Basically white blood cells

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14
Q

What are monocytes

A

Agranulocytes:
Monocytes:They are the largest of the formed elements. Their cytoplasm tends to be abundant and relatively clear. They function in differentiating into macrophages, which are large phagocytic cells, and digest pathogens, dead neutrophils, and the debris of dead cells. Like lymphocytes, they also present antigens to activate other immune cells.

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15
Q

What are granulocytes

A

Granulocytes are a type of white blood cell that has small granules inside them there are different types including basophils, Eosinophils, Neutrophils

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16
Q

What are basophils

A

Basophils:They have a pale nucleus that is usually hidden by granules. They secrete histamine which increases tissue blood flow via dilating the blood vessels, and also secrete heparin which is an anticoagulant that promotes mobility of other WBCs by preventing clotting.

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17
Q

What are eosinophils

A

Eosinophils:These have large granules and a prominent nucleus that is divided into two lobes. They function in the destruction of allergens and inflammatory chemicals, and release enzymes that disable parasites.

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18
Q

What are neutrophils

A

Neutrophils:These contain very fine cytoplasmic granules that can be seen under a light microscope. Neutrophils are also called polymorphonuclear (PMN) because they have a variety of nuclear shapes. They play roles in the destruction of bacteria and the release of chemicals that kill or inhibit the growth of bacteria.

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19
Q

Leukocyte order in blood

A

Neutrophils > Lymphocytes>Monocytes>Eosinophils >Basophils

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20
Q

What are natural killer cells

A

Lysis of viral infected cells and tumour cells

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21
Q

What are T helper cells

A

Release cytokines and growth factors that regulate other immune cells

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22
Q

What are cytotoxic T cells

A

Lysis of virally infected cells, tumour cells and allografts

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23
Q

What are Gamma delta T cells

A

Function : immunoregulation and cytotoxicity

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24
Q

What are b cells

A

Secretion of antibodies

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25
Red blood cell function
RBCs dedicated to respiratory gas transport Specialized to transport oxygen and carbon dioxide Major factor contributing to blood viscosity Life span 120 days
26
What happens as RBC ages
As a RBC ages, its membrane grows increasingly fragile.
27
Why can a RBC not repair themselves
Without key organelles such as a nucleus or ribosomes, RBCs cannot repair themselves.
28
Structure of RBC + Benefit
Structural characteristics biconcave discs anucleate No mitochondria or ribosomes essentially no organelles The benefit is that the cell has a greater ratio of surface area to volume, enabling O2 and CO2 to diffuse quickly to and from Hb.
29
How do RBC have energy with no mitochondria?
ATP production anaerobic; do not consume O2 they transport
30
The plasma membrane of RBC
The plasma membrane of a mature RBC has glycoproteins and glycolipids that determine a person’s blood type. On its inner surface are two proteins called spectrin and actin that give the membrane resilience and durability. This allows the RBCs to stretch, bend and fold as they squeeze through small blood vessels, and to spring back to their original shape as they pass through larger vessels.
31
What are RBC filled with
Filled with haemoglobin (Hb) for gas transport >97% haemoglobin (not counting water)
32
Haemoglobin Structure
Haemoglobin binds reversibly with oxygen Specialized protein haemoglobin carries the O2 Globin is a large protein composed of 4 polypeptide chains (tetramer) Two alpha and two beta chains Each RBC contains 200 -300 million Hb molecules
33
Haemoglobin normal values
Normal values Males: 130–180g/L Females: 120–160 g/L
34
What is haem
Haem is bonded to each globin chain Gives blood red colour
35
What is haem made of
Haem is made of an organic part a protoporphyrin ring made up of four pyrrole rings central iron ion in the ferrous state (Fe2+). 
36
How much can O2 can Haemoglobin transport
Each Hb molecule can transport four O2
37
O2 Unloading in tissues produces what?
Produces deoxyhaemoglobin or reduced hemoglobin (dark red)
38
What happens when O2 binds to one sub unit
When O2 binds to one subunit it induces a small change in the shape of Hb This makes the binding of the O2 next slightly easier
39
What is Haematopoiesis
- Adult humans produce approximately 2.3 million red blood cells every second, or 138 million every minute - All cells of the blood originate from stem cells in the bone marrow - haematopoietic stem cells (HSCs)
40
What is the formation of red cells called
The formation of red cells - erythropoiesis
41
What is the formation of Granulocytes and monocytes called?
myelopoiesis
42
What is the formation of platelets called?
Platelets - thrombopoiesis
43
How much new RBC made each day?
Each day we make around 10^12 new RBCs
44
Where does Process of development of RBC take place
This process occurs in the bone marrow
45
What is Proerythroblast (normoblast)
Normoblasts is a large cell with dark blue cytoplasm - A central nucleus with nucleoli Playing a crucial role in the development of mature red blood cells in the bone marrow.
46
As the normoblast develops into an erythrocyte it undergoes a series of divisions
- Getting smaller - Increasing amount of haemoglobin - Losing RNA and protein synthesis apparatus
47
Regulation of Erythropoiesis
- Too few RBCs leads to tissue hypoxia - Too many RBCs increases blood viscosity Balance between RBC production and destruction depends on: - Hormonal controls - Adequate supplies of iron, amino acids, and B vitamins
48
Effects of EPO
- Rapid maturation of committed marrow cells - Increased circulating reticulocyte count in 1–2 days Testosterone enhances EPO production, resulting in higher RBC counts in males
49
Hormonal Control of Erythropoiesis
Low O2 levels (hypoxia) in blood stimulate kidneys to produce erythropoietin
50
Causes of hypoxia:
- Decreased RBC numbers due to haemorrhage or increased destruction - Insufficient haemoglobin per RBC (e.g., iron deficiency) - Reduced availability of O2 (e.g., high altitudes)
51
What is Erythropoiesis
Erythropoiesis is the process by which red blood cells (erythrocytes) are produced in the bone marrow, starting from hematopoietic stem cells and culminating in mature, oxygen-carrying erythrocytes.
52
How does the process of erythropoietin work?
1) Low O2 levels in blood stimulate kidneys to produce erythropoietin. 2) Erythropoietin levels rise in blood. 3) Erythropoietin and necessary raw materials in blood promote erythropoiesis in red bone marrow. 4) New erythrocytes enter bloodstream; function about 120 days.
53
Dietary Requirements for Erythropoiesis
- Nutrients—amino acids, lipids, and carbohydrates - Iron - Available from diet 65% in Hb; rest in liver, spleen, and bone marrow - Free iron ions are toxic - Stored in cells as ferritin and haemosiderin - Transported in blood bound to protein transferrin - Vitamin B12 (cobalamin) and folic acid necessary for DNA synthesis for rapidly dividing cells (developing RBCs)
54
What is transferrin
- Transferrin is the protein that transports iron around the body - The liver synthesizes transferrin and secretes it into the plasma.
55
Fate and Destruction of Erythrocytes
Life span: 100–120 days Recycled in the spleen
56
Erythrocyte Disorders - Anaemia
Three main causes: - Blood loss - Low RBC production - High RBC destruction Accompanied by fatigue, pallor, shortness of breath, and chills
57
Haemorrhagic anaemia
Haemorrhagic anaemia resulting from excessive blood loss - Acute - Blood loss rapid (e.g., stab wound) Treated by blood replacement - Chronic Slight but persistent blood loss (e.g. haemorrhoids, bleeding ulcer) Primary problem treated
58
Iron Deficiency Anaemia (IDA)
- Treated with iron supplements - Most common cause of anaemia - Prevalence of 2–5% among adult men and post-menopausal women in the developed world - Caused by haemorrhagic anaemia, low iron intake, or impaired absorption - RBCs are small (microcytic) and pale (hypochromic)
59
What is haemostasis?
The mechanism for dealing with bleeding and clotting is called haemostasis Haemostasis comes from the Greek - heme meaning blood and stasis to halt
60
What does Normal Haemostasis do?
Maintain the fluidity of circulating blood Limit and arrest bleeding following injury by formation of a blood clot whilst at the same time maintaining blood flow through the damaged vessel Removal of a blood clot upon completion of wound healing
61
What's involved in haemostasis and why must it be tightly controlled
compartments: The blood vessels The platelets The coagulation factors (soluble plasma proteins) -Must be tightly controlled Do not want uncontrolled bleeding or inappropriate clotting
62
Facts about platelets
- Anuclear (no nucleus) - 1-3μm in diameter - Normal = 150 – 400 x 109/L - Higher than normal thrombocytosis - Lower than normal thrombocytopenia - Each day, 100 billion platelets must be produced from megakaryocytes (MKs) to maintain the normal platelet count - Platelet circulate for 7-10 days
63
Role of Platelets
Their primary physiological role is in blood clotting Detect damaged vessel endothelium Accumulate at the site of the vessel injury initiate blood clotting to block the circulatory leak
64
Primary, secondary haemostatic plug?
They are involved in ALL stages of haemostasis Primary haemostatic plug (platelet to platelet interactions) Secondary haemostatic plug (platelet – coagulation protein interactions) Involved in tissue injury, inflammation and wound healing by attracting and binding leukocytes
65
What are Megakaryocytes
Largest (50-100µm) and rarest cells in BM Polyploidal (More than one nucleus) Unique to mammals Can produce ~3000 platelets (compared to 2 daughter cells in other lineages) Platelet formation is far more complicated than the production of white cells
66
Platelet Production Stage 1
Phase I Megakaryocyte maturation - Endomitosis (DNA replication without cell division) - Cytoplasm enlargement (cytoskeletal proteins and platelet granules)
67
Platelet production stage 2
Platelet generation - Mature megakaryocytes extend long branching processes (proplatelets) - Organelles and granules are transported to proplatelets Driven by the cytoskeleton Stimulated by thrombopoietin (TPO
68
Summary of Platelet Activation
Protection by endothelium is lost Balance is tipped in favour of thrombosis Platelets stick to collagen and von Willebrand Factor (VWF) at site of blood vessel damage Platelets become activated, change shape, release granules and aggregate
69
What is haemostasis and what does it require?
- Fast series of reactions for stoppage of bleeding - Requires clotting factors, and substances released by platelets and injured tissues
70
What are the steps for haemostasis?
Three steps: 1) Constriction of blood vessels (vasoconstriction) 2) Platelet plug formation 3) Coagulation (blood clotting)
71
How does Vasoconstriction work
- Direct injury to vascular smooth muscle - Chemicals released by endothelial cells and platelets - Pain reflexes
72
What happens to the platelet plug
- Platelet plug is not stable needs to be reinforced - Platelet plug reinforced with fibrin threads - Happens through a series of reactions using clotting factors (procoagulants proteins)
73
Why do platelet plugs need replacing
Platelet plugs, the initial response to blood vessel damage, are temporary and need replacement with a stronger, more permanent clot (fibrin clot) to effectively stop bleeding and allow for tissue repair.
74
What is coagulation
Coagulation is a step wise series of reactions that lead to the conversion of fibrinogen to fibrin
75
Why is the conversion of fibrinogen to fibrin important
The conversion of fibrinogen to fibrin is crucial for blood clot formation, a process essential for hemostasis (stopping bleeding) and wound healing, as fibrin forms a stable meshwork that traps blood cells and platelets, preventing excessive blood loss
76
What is Fibrinolysis
Fibrinolysis breakdown of clots - Removes clots after healing - Begins within two days; continues for several
77
What 2 mechanisms limit clot size
Two mechanisms limit clot size: - Swift removal and dilution of clotting factors - Inhibition of activated clotting factors
78
Disorders of Haemostasis
1) Thromboembolic disorders: undesirable clot formation 2) Bleeding disorders: abnormalities that prevent normal clot formation
79
Thromboembolic Conditions
- Thrombus: clot that develops and persists in unbroken blood vessel - Embolus: thrombus freely floating in bloodstream - Embolism: embolus obstructing a vessel - Risk factors – atherosclerosis, inflammation, slowly flowing blood or blood stasis from immobility
80
Antithrombotic Drugs
- Aspirin - Cyclooxygenase inhibitor, that blocks thromboxane A2 synthesis and inhibits platelet aggregation - Heparin - Anticoagulant used clinically for pre- and postoperative cardiac care - Warfarin - Used for those prone to atrial fibrillation, interferes with action of vitamin K - Apixaban, Rivaroxaban - Factor X Inhibitors (DOACs (direct oral anticoagulants)/NOACs (novel oral anticoagulants)
81
Bleeding Disorders
- Thrombocytopenia - deficient number of circulating platelets - Haemophilia includes several similar hereditary bleeding disorders - Von Willebrand’s Disease most common inherited bleeding disorder.