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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