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BIO 124 Lecture 4

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BIO 124 Lecture 4

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BIO 124

Anatomy, Pathology & Pathophisiology


(3 Credit Hours)

Mohamed Lamin Sesay, PhD, MLS (ASCP)CM


Department of Biological Sciences
Faculty of Basic Sciences
Njala University
Cancer and Blood Clotting Disorders
What is Cancer?
• ​Cancer is a group of diseases characterized by the
uncontrolled proliferation of cells due to failure of contact
inhibition
• In healthy organisms, cell replication ceases when cells
come in contact with other cells – contact inhibition
• Malignant cells multiply to form tumors in organs and
tissues
• In the case of blood cancers, proliferated abnormal cells
crowd out normal cells in the blood stream and bone
marrow.
Cancers cont….
Types of Tumour
• Classified based on its ability to undergo metastasis
(spreading):
• Benign Tumour
• Localized at a particular location in the body
• Does not spread to the other parts of the
• Generally harmless.
• Presence of benign tumour the brain, can be fatal.
• Surgery best option and it does not grow back.
Cancers cont….
Premalignant Tumour
• Has an increased risk of becoming cancer
• It is benign but has the characteristics of a
malignant tumour.
• No metastasis, but has potential to turn
cancerous.
• Benign tumours become premalignant and
eventually, malignant.
Cancers cont….
Malignant Tumour
• Cancerous tumours
• Grow quickly and spread to other
normal tissues of the body – metastasis
• Cancer cells metastasize when it gets into the
bloodstream or the lymph nodes
• Forms secondary tumours across various sites
in the body
Cancers cont….
Types of Cancer
Classified based on their cell origin. Cancer can be classified into:
• Carcinoma
• Originates from the epithelial cells
• Most common form of cancer
• Sarcoma
• Originates from the connective tissues such as cartilage, fat and bone tissues
• Melanoma
• Originates from melanocytes (pigment containg cells)
• Lymphoma
• Originates from B lymphocytes
• Leukaemia
• Originates from white blood cells
Blood Coagulation
• Blood coagulation or clotting is a process that
prevents excess blood loss due to injury or
trauma
• The blood clot or ‘coagulum’ is formed
through a series of reactions activated by
clotting factors that results in the formation of
a network of fibrin threads
• The network traps deformed and dead formed
elements (erythrocytes, leukocytes and
platelets) as well
Coagulating Factors
Blood Coagulation Pathway
• Clotting is initiated by injury
• Injury stimulates thrombocytes to release
various factors that initiate the blood clotting
cascade.
• Process is calcium ions dependent
• Through cascade of reactions, prothrombin is
converted by throbokinase to active thrombin

Pathway cont….
• Fibrinogen or factor I is converted to fibrin by
thrombin.
• Thrombin forms fibrin monomers that polymerize
to form cross-linked fibrin mesh that plug the
bleeding
• Two process involved:
– Primary haemostatis – platelet aggregation to form a
plug
– Secondary haemostasis- stabilization of plt plug
through formation of network of fibrin threads
Pathway cont….
Primary Haemostasis - Platelet Aggregation
• Damage to blood vessel endothelium
• Platelets adhere to exposed collagen
• Adhesion is stimulated by the von Willebrand
factor released from endothelial cells and
platelets
• Facilitate tight binding and aggregation of
platelets at the site of injury
• Primary haemostasis is established
Pathway cont….
Secondary Haemostasis
• The three main steps of the blood coagulation
cascade are as follows:
1. Formation of prothrombin activator
– Intrinsic pathway
– Extrinsic pathway
2. Conversion of prothrombin to thrombin
3. Conversion of fibrinogen into fibrin
Blood Coagulation Pathway
Pathway cont….
1. Formation of prothrombin activator
I. Intrinsic pathway
II. Extrinsic pathway
I. Intrinsic pathway
• Exposure of collagen to blood activates the plasma factor XII to
XIIa
• Factor XIIa activates the factor XI to XIa.
• The XIa then activates the factor IX to IXa in the presence of
Ca2+ ions.
• The factor IXa in the presence of factor VIIIa, Ca2+ and
phospholipids activate factor X to Xa.
• Factor Xa is the active factor that activates prothrombin
Pathway cont….
II. Extrinsic pathway
• Damaged vascular walls release tissue factors
or tissue thromboplastins
• Tissue factor activates factor VII to VIIa.
• Factor VIIa activate factor X to Xa in the
presence of Ca2+.
• Factor Xa is the active factor that activates
prothrombin
Pathway cont….
• The factor Xa, factor V, phospholipids and
calcium ions form the prothrombin activator
2. Conversion of prothrombin to thrombin
• The prothrombin activator converts
prothrombin or factor II to thrombin.
– Vit. K needed for prothrobim synthesis in liver
• Thrombin activates factors VIII, V and XIII
Pathway cont….
3. Conversion of fibrinogen into fibrin
• Thrombin converts fibrinogen or factor I to fibrin
• Thrombin forms fibrin monomers that polymerize to
form long fibrin threads.
• Thrombin also activates factor XIII (fibrin stabilizing
factor) to active factor XIIIa
• Activated factor XIIIa forms cross-linking between
fibrin threads in the presence of Ca2+ to stabilize the
fibrin meshwork
• The fibrin mesh traps the formed elements to form a
solid mass called a clot.
Blood Clotting Disorders

• Blood clotting is a haemostatic process that


prevents bleeding when injure
• Blood clotting disorder either prevents blood
clotting, or causes hypercoagulation where your
blood forms clot too easily due to the lack of
clotting factors (haemophilia) or over activity
(thrombosis)
• Blood clot is a mass of coagulated blood that
contains RBCs, WBCs and platelets entrapped in
fibrin meshwork
Disorders cont…
1. Haemophilia
• Clotting disorder characterized by excessive bleeding.
• Caused by the lack of some of the factors required in
the blood clotting cascade.
• Three forms:
• Haemophilia A – Factor VIII deficiency
• Haemophilia B – Factor IX deficiency or “Christmas
disease”
• Haemophilia C – Factor XI deficiency
Disorders cont…
2. von Willebrand’s disease
• Genetic disorder that prevents clotting due to
insufficient von Willebrand factor, a blood-
clotting protein
• Commonly noticed in females than males
– Abnormally heavy bleeding during menstrual
periods or birth.
Disorders cont…
3. Thrombosis
• Formation of a blood clot inside an intact blood vessel.
• Blocks the flow of blood.
• Occur in arteries or veins
• Arterial thrombosis damage tissue, i.e. ischemia or
necrosis.
• Clot may sometimes break free and circulate in the
body causing:
– Deep vein thrombosis
– Pulmonary embolism.
Disorders cont…
• Circulating blood clot can increase the risk of:
– Stroke
– Heart attack
– Severe leg pain
– Difficulty walking

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