Impaired Blood Flow and Bodily Fluids PDF

IMPAIRED BLOOD FLOW AND OTHER BODILY FLUID Dr Norsyahida Mohd Fauzi Lecturer in Biopharmacy and Pharmacology Discipline, Member of Drug and Herbal Res...

IMPAIRED BLOOD FLOW AND OTHER BODILY FLUID Dr Norsyahida Mohd Fauzi Lecturer in Biopharmacy and Pharmacology Discipline, Member of Drug and Herbal Research Centre LECTURE OBJECTIVES At the end of this lecture, student should be able to: ▪ describe about haemodynamic disorders. ▪ describe about thromboembolism ▪ describe about shock INTRODUCTION In normal condition: - Plasma protein retain in blood vessel. - Little net movement of water & electrolyte into tissues. Pathologic condition: - The balance of the above condition is altered. - How? 1. Alter endothelial function. 2. ↑ vascular pressure 3. ↓plasma protein content HYPERAEMIA AND CONGESTION Hyperaemia and congestion: both ↑volume within a tissue. But have different mechanism Hyperaemia :active process, arteriolar dilation and increased blood inflow. Occurs at sites of inflammation or in exercising skeletal muscle. (RED) Congestion: passive process, impaired outflow of venous blood from a tissue (BLUE) OEDEMA ▪ Edema is the result of the movement of fluid from the vasculature into the interstitial spaces. ▪ The fluid may be protein-poor (transudate) or protein-rich (exudate) ▪ Fluid may also accumulate in body cavities: -Hydrothorax -Hydropericardium -Hydroperitoneum (Ascites) ▪ Massive generalized oedema is called anasarca. CAUSES OF OEDEMA Homeostasis is maintained by the opposing effects of Vascular Hydrostatic Pressure and Plasma Colloid Osmotic Pressure. Imbalance of this pressures will cause oedema. Four causes of oedema: Increased Hydrostatic Pressure Reduced Plasma Osmotic Pressure Lymphatic Obstruction –inflammation and neoplasia Sodium and Water Retention - renal failure Increased vascular permeability - Inflammation INCREASED HYDROSTATIC PRESSURE ▪ Impaired venous return: - Local venous pressure: DVT (local oedema) - Generalized venous pressure: E.g., Congestive heart failure (generalized oedema) due to Increased central venous pressure and decreased renal perfusion. ▪ Increased arteriolar dilation CONGESTIVE HEART FAILURE REDUCED PLASMA OSMOTIC PRESSURE Albumin accounts for almost half of the total plasma protein and are responsible for the maintenance of colloid osmotic pressure. A decrease in of colloid osmotic pressure can occur due to: ▪ Reduced synthesis of albumin (cirrhosis, protein malnutrition) ▪ Increased loss of albumin (nephrotic syndrome- increased permeability of the glomerular capillary wall that lead to loss of protein) LYMPHATIC OBSTRUCTION ▪Impaired lymphatic drainage leads to lymphedema ▪Localised oedema. ▪Usually due to inflammation, complication of therapy or neoplastic obstruction. Example: 1. parasitic infection affecting inguinal lymphatics resulting in elephantiasis. 2. Radiation to axillary lymphatics in breast cancer patients can lead to arm oedema. 3. Carcinoma of breast with obstruction of superficial lymphatics can lead to oedema of breast skin. MORPHOLOGY OF OEDEMA ▪ Gross inspection: enlargement of organs ▪ Microscopic examination : shows clearing and separation of the extracellular matrix elements. HAEMORRHAGE Hemorrhage: extravasation of blood from vessels In hemorragic diatheses trauma, atherosclerosis, A. Hemorrhages of the colonic mucosa, a consequence of thrombocytopenia. B. Fatal intracerebral hemorrhage. Hemorrhage may be manifested by different appearances and clinical consequences. Hematoma: trivial to fatal Petechia Purpura Ecchymoses Large bleeds into body cavities: named according to location. E.g., Hemopericardium- at pericardium Clinical significance depend on: - volume and rate of blood lost - site of haemorrhage HAEMOSTASIS AND THROMBOSIS Normal haemostasis - maintain blood in a fluid, clot-free state in normal vessels - Rapidly forming a localized haemostatic plug at the site of vascular injury. Pathologic haemostasis - Thrombosis : blood clot within intact vessels HAEMOSTASIS ▪ Vasoconstriction ▪ Primary hemostasis (platelet aggregation forming primary hemostatic plug) ▪ Secondary hemostasis (more stable, contains RBC and leukocytes) ▪ Antithrombotic (fibrinolysis; degrade thrombi ROLES OF ENDOTHELIUM Endothelial cells are central regulators of hemostasis Antithrombotic properties - inhibitory effects on platelet - inhibitory effects on coagulation factors - fibrinolysis Prothrombotic properties - activation of platelets - Activation of clotting factor - Antifibrinolytic effect ROLES OF PLATELET 1. Platelet adhesion 2. Platelet activation 3. Platelet aggregation ROLES OF COAGULATION CASCADE ▪ Tissue factor : initiate the coagulation cascade. ▪ At the final stage of coagulation: thrombin converts fibrinogen into insoluble fibrin, forming hemostatic plug. THROMBOSIS MORPHOLOGY Arterial or cardiac thrombi - Endothelial injury Venous thrombi - At sites of stasis Mural thrombi (in heart chamber/ aorta) Vegetations: thrombi in heart valves FATE OF THROMBUS Propagation Embolization Dissolution Organization and recanalization CLINICAL CORRELATION Can cause obstruction and embolism Arterial thrombosis - obstruct coronary and cerebral vessel causing myocardial infarction and stroke. Venous thrombosis - DVT prone to embolised to the lung EMBOLISM An embolus - is an intravascular solid, liquid, or gaseous mass - is carried by the blood to a site distant from its point of origin. Derived from a dislodged thrombus (thromboembolism) Primary consequence: - systemic: infarction - Pulmonary circulation: hypoxia, right sided heart failure  TWO TYPES OF EMBOLI ▪ Pulmonary emboli: emboli that travel through venous. Mainly arise in the deep vein thrombosis. If large, can block pulmonary arteries and cause right side heart failure, pulmonary infarction or sudden death. ▪Systemic emboli : emboli that travel through artery. From cardiac mural (80%), valvular thrombi, aortic aneurysm, atherosclerotic plaque. FAT, AMNIOTIC FLUID AND AIR EMBOLISMS Fat embolism: Soft tissue crush injury or long bone fracture release fat globules into the circulation. Fat emboli occlude pulmonary and cerebral vasculature. Amniotic fluid: entry of amniotic fluid and its contents into the maternal circulation vi tears in the placental membrane or uterine rupture. Air: Gas bubbles within the circulation obstruct vascular flow. E.g., 1) Small volume of air trapped in coronary artery during bypass surgery. 2)decompression sickness that is caused by sudden changes in atmospheric pressure (A scuba diver ascends too rapidly, nitrogen bubbles of solution in he blood) INFARCTION An infarct - is an area of ischemic necrosis caused by occlusion of the vascular supply to the affected tissue. Important cause of clinical illness Can occur in: - artery (most common- due to thrombosis and embolisation) - vein (less frequent) Example: myocardial, cerebral and pulmonary infarction MORPHOLOGY Infarcts are classified on: a) colour - Red (haemorrhagic) e.g., venous occlusion such as ovarian torsion; in loose tissue (lung) - White (anaemic) - e.g., arterial occlusion in solid organ such as heart, spleen and kidney b) Presence/absence of microbial infection - Septic (presence of infection) - Bland (absence of infection) MORPHOLOGY-HISTOLOGY In most tissues infarction: ischemic coagulative necrosis Brain infarction: liquefactive necrosis Septic infarctions : The infarct is converted into an abscess. FACTORS THAT INFLUENCE INFARCT DEVELOPMENT 1. The anatomy of the vascular supply 2. Rate of occlusion 3. Tissue vulnerability to ischaemia 4. Hypoxemia. SHOCK Shock is the final common pathway for several potentially lethal events. E.g., - Exsanguination - extensive trauma or burns - myocardial infarction - pulmonary embolism - sepsis. THREE MAJOR TYPES OF SHOCK ▪ Cardiogenic- failure of myocardial pump,↓ cardiac output (e.g., MI, arrhythmia) ▪ Hypovolemic- inadequate blood/plasma volume, ↓ cardiac output (e.g., haemorrhage, diarrheoa, burns) ▪ Septic-systemic immune response to microbial infection (e.g., endotoxic shock, fungal sepsis)