Human Biological Science 2 Lesson 2 · Human Biological Science 2 Session 2 Haematological System ... ATP, Ca+2, serotonin, fibrin-stabilizing factor, and enzymes that produce thromboxane

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BIOH122Human Biological Science 2

Session 2

Haematological System –

Haemostasis and Blood

Groups

Bioscience Department

© Endeavour College of Natural Health endeavour.edu.au 2

Session Plan

o Platelets• Properties

• Functions

• Thrombopoiesis

o Haemostasis• vascular spasm

• platelet plug formation

• blood clotting

o Blood Groups and Blood Types• ABO Blood Groups

• Rh Blood Groups

o Hematological Disorders


Platelets


Platelets: Thrombocyte

o Shape: Irregularly disc-shaped, Cell fragments

o Size: 2 - 4 micron in diameter

o Structure: contains many vesicles but no nucleus

o Life span: only 5 to 9 days;

• aged and dead platelets are removed by fixed macrophages in

the spleen and liver.

o Normal platelet count: 150,000-400,000/µL of blood

o Function: help stop blood loss from damaged vessels by

forming a platelet plug. Their granules also contain

chemicals that promote blood clotting.

Tortora, GJ & Derrickson, B 2012. Principles of Anatomy

and Physiology, 13th edn, John Wiley & Sons, New York.


Thrombopoiesis: Making Platelets

o Thrombopoietin stimulates myeloid stem cells to produce

platelets in bone marrow.

.



Each megakaryocyte splits into 2000 to

3000 fragments, enclosed by a piece of

cell membrane. This is a platelet

(thrombocyte).


Haemostasis:Blood Clotting


Haemostasis

o Stoppage of bleeding in a quick and localized fashion

when blood vessels are damaged

o Prevents haemorrhage (loss of a large amount of blood)

o Mechanisms:

• Vascular spasm

• Platelet plug formation

• Blood clotting (coagulation = formation of fibrin

threads)


Vascular Spasm

o Reflex contraction of smooth muscle of small blood

vessels when arteries or arterioles are damaged.

o Caused by damage to the smooth muscle of blood

vessel, by substances released from activated platelets,

and by reflexes initiated by pain receptors.

o Can reduce blood loss for several hours until other

mechanisms can take over

o Only for small blood vessel or arteriole.


Platelet Plug Formation

o Platelets store a lot of chemicals in granules needed for

platelet plug formation

• Alpha granules

– Clotting Factors (for coagulation cascade)

• Dense granules

– ADP, ATP, Ca+2, serotonin, fibrin-stabilizing factor,

and enzymes that produce thromboxane A2


Platelet Plug Formation

o Platelet Adhesion

• platelets stick to exposed collagen and

damaged endothelial cells in vessel wall

o Platelet Release Reaction

• platelets “activated” by adhesion

• extend projections & make contact

• release thromboxane A2, ADP, serotonin

o Platelet Aggregation

• activated platelets stick together to form

a mass called a ‘platelet plug’

• plug reinforced by fibrin threads formed

during clotting processTortora, GJ & Derrickson, B 2012. Principles of Anatomy



Blood Clotting

o Blood drawn from the

body thickens into an

insoluble protein gel

o This gel separates into

liquid (serum) and a clot

of insoluble fibers (fibrin)

in which the formed

elements are trapped




Blood Clotting

o Coagulation factors required for clotting are mostly in

blood plasma

o Identified by Roman numerals

o Include:

• Ca+2, inactive enzymes synthesized by liver cells and

substances released by platelets or damaged tissues

o Thrombosis: Blood clots too easily and clotting occurs in

an unbroken vessel

o Haemorrhage: Blood takes too long to clot


Blood Clotting Factors




Blood Clotting Cascade

o Clotting is a cascade of reactions in which each clotting

factor activates the next in a fixed sequence resulting in

the formation of fibrin threads

o Key Steps

• Formation of prothrombinase

• Prothrombinase and Ca+2 convert prothrombin into

thrombin

• Thrombin converts soluble fibrinogen into insoluble

fibrin threads


Overview of the Clotting Cascade



Formation of prothrombinase

Prothrombinase and Ca+2 convert

prothrombin into thrombin

Thrombin converts soluble

fibrinogen into insoluble fibrin

threads

Extrinsic and Intrinsic Pathway


Extrinsic Pathway

o Damaged tissues leak

tissue factor

(thromboplastin) into

bloodstream

o Prothrombinase forms in

seconds




Intrinsic Pathway

o Activation occurs

• endothelium is damaged

and platelets come in

contact with collagen of

blood vessel wall

• platelets are damaged

releasing phospholipids

o Requires several minutes

for Prothrombinase to be

produced


Final Common Pathway

o Prothrombinase + Ca+2

• catalyze the conversion of

prothrombin → thrombin

o Thrombin + Ca2+

• converts fibrinogen → fibrin threads

• activates fibrin stabilizing factor XIII

Strengthened Fibrin threads & Clot

retraction




Clot Retraction

o Clots plug the ruptured

area of the blood vessel

o Platelets pull on fibrin

threads causing clot

retraction (tightening)

• trapped platelets

release factor XIII

stabilizing the fibrin

threads

http://www.austincc.edu/apreview/PhysText/Blood.htm


Clotting Cascade : Positive Feedback

o Positive feedback effects of

thrombin

o Thrombin

• accelerates formation of

prothrombinase

• activates platelets to

release phospholipids

+


Blood Vessel Repair

Blood Vessel Repair:

o Edges of damaged vessel are pulled together

o Fibroblasts and endothelial cells repair the blood vessel


Role of Vitamin K in Clotting

o Adequate vitamin K is required for Normal clotting

• Fat soluble vitamin absorbed if lipids are present

• Absorption slowed if bile release is insufficient

o Required for synthesis of 4 clotting factors by

hepatocytes

• Factors II (prothrombin), VII, IX and X

o Produced by bacteria in large intestine


Haemostatic Control Mechanisms

o Fibrinolytic system dissolves small, inappropriate clots

and clots at a site of a completed repair

• fibrinolysis is dissolution of a clot

o Inactive plasminogen is incorporated into the clot

• plasminogen becomes plasmin (fibrinolysin) which

digests fibrin threads and inactivating fibrinogen,

prothrombin, factors V, VIII, XII


Haemostatic Control Mechanisms

o Clot formation remains localized

• fibrin threads trap / absorbs thrombin

• blood disperses clotting factors

o Endothelial cells and WBC produce prostacyclins that

oppose thromboxane A2 (platelet adhesion and release)

o Anticoagulants are present in blood and are produced by

mast cells


Haemostatic Disorders

o Thrombosis: Clotting in an unbroken blood vessel

• Involves the Intrinsic pathway

o Embolus: A thrombus (clot), bubble of air, fat from broken

bones, or piece of debris transported by the bloodstream

that moves from its site of origin.


Anticoagulant Agents

o Anticoagulants: suppress or prevent blood clotting

o Patients who are at increased risk of forming blood clots

may receive an anticoagulant drug

• Aspirin inhibits vasoconstriction and platelet aggregation

through stopping production of Tx A2.

• heparin

– administered during haemodialysis and surgery

• warfarin (Coumadin®)

– antagonist to vitamin K so blocks synthesis of clotting

factors

– slower than heparin


Thrombolytic Agents

o Thrombolytic agents: are injected to dissolve clots

• streptokinase or tissue plasminogen activator (t-PA)

o Directly or indirectly activate plasminogen

• Used to dissolve coronary cerebral & pulmonary clots


Blood Groups and Blood Types


ABO Group

o Agglutinogens: surface Antigens on Erythrocytes

• A or B, then both A and B, or neither called O

o In the ABO system, Agglutinogens A and B found on the

surface of RBCs determine blood types

• display only antigen A - blood type A

• display only antigen B - blood type B

• display both antigens A and B - blood type AB

• display neither antigen - blood type O


ABO Blood Groups

o Agglutinins : Antibodies present in plasma designated

as anti-A and anti-B, that react with agglutinogens that

are foreign to the individual.

• anti-A antibody reacts with antigen A

• anti-B antibody reacts with antigen B


Blood Groups and Blood Types

o RBC surfaces are marked by genetically determined glycoproteins and glycolipids

• distinguishes at least 24 different blood groups

– ABO, Rh, Lewis, Kell, Kidd and Duffy systemsTortora, GJ & Derrickson, B 2012. Principles of Anatomy



Rh Blood Groups

o Rh: Antigen was discovered in blood of Rhesus monkey

o People with Rh agglutinogens on RBC surface are

Rh+ve. Normal plasma contains no anti-Rh antibodies

o Antibodies develop only in Rh-ve blood type and only

with exposure to the antigen

• transfusion of positive blood

• during a pregnancy with a positive blood type foetus

o Transfusion reaction upon second exposure to the

antigen results in haemolysis of the RBCs in the donated

blood


Haemolytic Disease of Newborn

o Rh negative mother and Rh+ foetus will have mixing of blood at birth

o Mother's body creates Rh antibodies unless she receives a RhoGam shot soon after first delivery, miscarriage or abortion

• RhoGam binds to loose foetal blood and removes it from her body before she reacts

o In her second pregnancy, haemolytic disease of the newborn may develop causing haemolysis of the foetal RBCs


Haemolytic Disease of Newborn




Transfusions

o Transfusions: Transfer of whole blood, cells or plasma

into the bloodstream of recipient

• used to treat anaemia or severe blood loss, clotting disorders,

cancers, burns

o Knowledge of blood type:

• Essential for safe transfusion of blood

• Forensics

• Anthropology studies to establish a relationship among races.


Transfusion Reactions

o Incompatible blood transfusions

• antigen-antibody complexes form between plasma

antibodies and “foreign proteins” on donated RBC's

(agglutination)

• donated RBCs become leaky (complement proteins)

and burst

• loose haemoglobin causing kidney damage


Universal Donors and Recipients

o Universal recipients: People with type AB blood are called

as they have no antibodies in plasma*

o Universal donors: People with type O blood cell since they

have no antigens on their cells*

*only true if cross match the blood for other antigens


Hematological Disorders


Hematological Disorders

o Anaemia

o Sickle-cell

o Haemophilia

o Disseminated intravascular clotting

o Acute leukaemia

o Chronic leukaemia


Anaemia

Anaemia:

o Symptoms

• oxygen-carrying capacity of blood is reduced

• fatigue, cold intolerance and paleness

– lack of O2 for ATP and heat production


Anaemia

o Types of anaemia

• Iron-deficiency = lack of absorption or loss of iron

• Pernicious = lack of intrinsic factor for B12 absorption

• Haemorrhagic = loss of RBCs due to bleeding (ulcer)

• Haemolytic = defects in cell membranes cause

rupture

• Thalassemia = hereditary deficiency of haemoglobin

• Aplastic = destruction of bone marrow

(radiation/toxins)


Sickle-Cell Anaemia (SCA)

Sickle-Cell Anaemia

o Genetic defect in haemoglobin molecule (Hb-S) that

changes 2 amino acids

• at low very O2 levels, RBC is deformed by changes in

haemoglobin molecule within the RBC

– sickle-shaped cells rupture easily

– causing anaemia and clots




Haemophilia

Haemophilia: Inherited deficiency of clotting factors

o Symptoms:

• bleeding spontaneously or after minor trauma

• subcutaneous and intramuscular haemorrhaging

• nosebleeds, blood in urine, articular bleeding and

pain


Haemophilia

o Types of Haemophilia:

• Haemophilia A lacks factor VIII (males only)

• Haemophilia B lacks factor IX (males only)

• Haemophilia C (males and females)

o Treatment is transfusions of fresh plasma or

concentrates of the missing clotting factor


Leukaemia

o Acute leukaemia

• uncontrolled production of immature leukocytes

• crowding out of normal red bone marrow cells by

production of immature WBC

• prevents production of RBC and platelets

o Chronic leukaemia

• accumulation of mature WBC in bloodstream because

they do not die

• classified by type of WBC that is predominant -

monocytic, lymphocytic


Readings and Resources

o Tortora, GJ & Derrickson, B 2014. Principles of Anatomy and Physiology, 14th edn, Wiley.

o Harris, P, Nagy, S & Vardaxis, N 2010, Mosby’s Dictionary of Medicine, Nursing and Health Professions, 2nd edn, Mosby Elsevier.

o Guyton, AC & Hall, JE 2011, Textbook of Medical Physiology, 12th edn, Saunders Elsevier.

o Marieb, EN & Hoehn, K 2010, Human Anatomy and Physiology, 8th edn, Benjamin Cummings Pearson.

o Moore, KL, Dalley, AF & Agur, AMR 2010, Clinically Orientated Anatomy, 6th edn, Lippincott, Williams & Wilkins.


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Human Biological Science 2 Lesson 2 · Human Biological Science 2 Session 2 Haematological System ... ATP, Ca+2, serotonin, fibrin-stabilizing factor, and enzymes that produce thromboxane