Thrombus Types and Sequelae of Thrombosis

Thrombosis and Embolism

• Thrombosis is the process of forming a solid or semi-solid mass from blood constituents within the vascular system during life.
• The mass formed is called a thrombus (plural = thrombi).
• Embolism is the transfer of abnormal material by the bloodstream and its subsequent lodgement in the vessels downstream.
• The mass of abnormal material is called an embolus (plural = emboli).
• Infarction is an area of anoxic necrosis produced by an acute interference with a tissue's blood supply.

Types of Thrombi

• Mural thrombus: forms on the wall of a blood vessel
• Occlusive thrombus: completely blocks the vascular lumen
• Mixed thrombus: a combination of red and white thrombi
• Red thrombus: consists of red blood cells, fibrin, and platelets
• White thrombus: consists of platelets, fibrin, and white blood cells
• Propagating thrombus: enlarges along a vessel, involving more branches
• Ball thrombus: forms on a heart valve

Sequelae of Thrombosis

• Propagation: thrombus enlarges along a vessel, involving more branches
• Lysis: thrombus may resolve
• Calcification: thrombus undergoes necrosis and dystrophic calcification
• Infection: leading to abscesses or septic infarcts
• Retraction, organization, recanalization: organization of the thrombus into scar
• Thromboembolism: detachment and embolism which may lead to infarction
• Infarction: thrombus interrupts blood flow, anoxia and necrosis of tissue will result

Embolism

• An embolus can be a solid (e.g. dislodged thrombus), liquid (e.g. amniotic fluid embolus), or gas (e.g. air injected into the circulation)
• Venous thromboemboli: originate from deep leg veins or pelvic veins, lodge in pulmonary arteries, and may cause death or pulmonary infarcts
• Arterial thromboemboli: associated with atherosclerosis, may cause fatal myocardial infarcts (heart attacks) or cerebral infarcts (strokes)

Virchow's Triad

• Changes in the vessel wall (e.g. damage to the intima by atherosclerosis)
• Changes in the blood flow (e.g. stasis of blood - complete stoppage of flow)
• Changes in the blood constituents (e.g. increased clotting factors)

Atherosclerosis

• A disease of large arteries where lipid is deposited in the intima of vessels
• Narrows the lumen of the vessel, alters blood flow, and predisposes to thrombosis

Clinical Risk Factors for Thrombosis

• Increased age
• Heart conditions
• Health status
• Immobility
• Cigarette smoking

Other Conditions

• Haemarthrosis: haemorrhage into a joint
• Thrombocytopenic purpura: multiple small haemorrhages in the skin and mucous membranes due to low circulating platelet number
• Primary shock: low blood pressure mediated by a transient neurovascular reaction

Respiratory Infections and Inflammations

• Lobar pneumonia: whole lung lobe(s) affected; 8-day course; resolution
• Bronchopneumonia: affects age extremes; different flora; patchy lesions; irregular course; pus and fibrosis
• Tuberculosis: caseating granulomatous inflammation; airborne transmission of M. tuberculosis; tubercle formation
• Viral infections: influenza, rhinovirus, coxsackievirus, echovirus, SARS coronavirus, CMV
• Fungal infections: Aspergillus spp, Cryptococcus spp, Candida albicans, Pneumocystis jiroveci (previously P. carinii)
• Sarcoidosis: idiopathic; granulomatous inflammation; more common in women; immune anomalies; +ve Kveim-Siltzback skin test
• Adult Respiratory Distress Syndrome (ARDS): diffuse alveolar damage due to various factors; 70% die in acute phase

Pneumoconioses

• Organic: Byssinosis (cotton protein), Bagassosis (sugar cane refuse), Farmers' lung (mouldy hay), Suberosis (cork dust)
• Inorganic:
• Anthracosis: Carbon; most harmless of inorganic
• Silicosis: Silica; predisposes to TB; COPD, RH problems
• Silicoanthracosis: Carbon & silica; results as for silicosis
• Berylliosis: Beryllium; leads to granulomas, COPD
• Silicosiderosis: Silica & iron; predisposes to TB, lung malignancy
• Asbestosis: Asbestos; most harmful; leads to asbestosis, COPD, mesothelioma of pleura

Tumours

• Mesothelioma of the pleura: Exposure to asbestos; highly malignant; death usual within 10 months of diagnosis
• Tumours of the lungs: 1o (mesothelioma or bronchogenic carcinoma) or 2o (many tumours metastasize to the lungs)

Respiratory System Disorders

Congenital Disorders

• Bronchial atresia: Narrowing of bronchus
• Hypoplasia of lung: Smaller than normal
• Bronchogenic cysts: Contain much mucus
• Bronchopulmonary sequestration: Portion of lung does not communicate with bronchial tree
• Kartagener's Syndrome (immotile cilia syndrome): Defective cilia function
• Neonatal respiratory distress syndrome (NRDS): Deficiency of surfactant, alveoli collapse; atelectasis
• Cystic fibrosis:
• CF gene causes production of abnormal viscid mucus, cannot be cleared from lungs
• Recurrent infections; bronchiectasis & haemoptysis; hyperinflation & pneumothorax; necrosis, scarring; pulmonary HT & cor pulmonale

Respiratory System Disorders

• If left untreated, pneumonia, TB, and ARDS can have life-threatening outcomes.
• Pneumoconioses are dust inhalation disorders, often occupational, that can harm the lungs.
• Inorganic or mineral particles (e.g., asbestos) are more harmful than organic particles.
• Lung tumors can be primary (e.g., mesothelioma or bronchogenic carcinoma) or secondary (metastasizing to the lungs).

Congenital Disorders

• Bronchial atresia: narrowing of the bronchus
• Hypoplasia of the lung: smaller than normal lung
• Bronchogenic cysts: contain much mucus
• Bronchopulmonary sequestration: portion of the lung does not communicate with the bronchial tree
• Kartagener's Syndrome (immotile cilia syndrome): defective cilia function
• Neonatal respiratory distress syndrome (NRDS): deficiency of surfactant, alveoli collapse, and atelectasis

Cystic Fibrosis

• CF gene causes production of abnormal, viscid mucus that cannot be cleared from the lungs, leading to recurrent infections, bronchiectasis, and haemoptysis.
• Other symptoms include hyperinflation, pneumothorax, necrosis, scarring, pulmonary hypertension, and cor pulmonale.

Chronic Obstructive Pulmonary/Airways Disease (COPD/COAD)

• Characterized by persistent airflow limitation, dyspnoea, cough, and sputum production.
• Emphysema: loss of elastic recoil, decreased surface area of alveoli, and familial or acquired defects in α1-antiproteinase.
• Bronchiectasis: permanent dilatation of bronchi and bronchioles, leading to recurrent cough, copious mucus, and chronic infections.
• Chronic bronchitis and bronchiolitis: mucous hypersecretion, inflammation of airways, and airway narrowing.

COPD

• An "umbrella" term encompassing emphysema, bronchiectasis, chronic bronchitis, and bronchiolitis.
• Associated with damage to alveolar walls, muscle, and supporting elastic tissue.

Asthma

• Mediated by a Type I hypersensitivity, leading to bronchial constriction, bronchospasm, and excess mucus production.
• Triggers include extrinsic factors (allergens, environmental triggers) and intrinsic factors (exercise, stress, psychogenic triggers).
• Sequelae: mild disease, status asthmaticus, chronic asthma, and COPD.

Infections and Inflammations

• Lobar pneumonia: characterized by acute consolidation of one or more lobes of the lungs by Streptococcus pneumoniae infection.
• Other types of pneumonia include acute patchy consolidation of the lungs around bronchioles by Candida albicans infection and chronic inflammation of alveolar capillaries by Mycobacterium tuberculosis infection.

Pneumoconioses

• Organic: byssinosis (cotton protein), bagassosis (sugar cane refuse), farmer's lung (moldy hay), and suberosis (cork dust).
• Inorganic: anthracosis (carbon), silicosis (silica), silicoanthracosis (carbon and silica), berylliosis (beryllium), silicosiderosis (silica and iron), and asbestosis (asbestos).

Tumors

• Mesothelioma of the pleura: highly malignant, usually fatal within 10 months of diagnosis, and associated with asbestos exposure.

Pathology Study Guide Weeks 5-8

Carcinogenesis and Immunodeficiencies

• Carcinogenesis: the process of cancer initiation and promotion, involving genetic alterations in four classes of genes
• Aetiology of cancer: multifactorial, involving interaction of intrinsic and extrinsic factors, with carcinogens playing a part
• Primary immunodeficiencies:
  • Agammaglobulinaemia: deficiency of B cells
  • Thymic aplasia: deficiency of T cells
  • Combined immunodeficiency: deficiency of both T and B cells
• Secondary immunodeficiencies:
  • Miscellaneous causes such as ageing, infections, tumours, drugs, and radiation exposure
  • Infection with HIV → AIDS
• Hypersensitivities:
  • Type I: Immediate hypersensitivity, due to sensitized mast cells, IgE, and acute inflammation and tissue damage
  • Type II: Antibody-mediated hypersensitivity, due to IgG or IgM antibodies causing cell lysis, stimulation, or inhibition and tissue damage
  • Type III: Immune complex-mediated hypersensitivity, due to immune complex deposition and tissue damage
  • Type IV: T cell-mediated (delayed) hypersensitivity, due to sensitized lymphocytes and activated macrophages and tissue damage
• Autoimmune disorders: failure of self-recognition, reaction of immune system against body components, involving autoantigens and autoantibodies, and cell-mediated immune mechanisms

Hypertension and Arteriosclerosis

• Infarction: process of anoxic necrosis of tissue due to acute interference with blood supply
• Hypertension: persistent rise in systemic blood pressure to levels >140/90 mmHg
• Aetiological subtypes:
  • Primary hypertension (idiopathic, multifactorial)
  • Secondary hypertension (renal, renal artery stenotic, endocrine, or iatrogenic causes)
• Clinical subtypes:
  • Benign hypertension (long course, renal function preserved, patients more likely to have cardiac disease)
  • Malignant hypertension (rapid deterioration of kidney function, characteristic lesion is "onion skinning" of vessels)
• Arteriosclerosis: loss of elasticity and hardening of arteries
• Myocardial infarction (MI): due to coronary artery insufficiency, atherosclerosis, and/or thrombus formation

Respiratory System Disorders

• Congenital disorders:
  • Bronchial atresia: narrowing of bronchus
  • Hypoplasia of lung: smaller than normal
  • Bronchogenic cysts: contain much mucus
  • Bronchopulmonary sequestration: portion of lung does not communicate with bronchial tree
  • Kartagener's Syndrome (immotile cilia syndrome): defective cilia function
  • Neonatal respiratory distress syndrome (NRDS): deficiency of surfactant, alveoli collapse, atelectasis
• Cystic fibrosis:
  • Abnormal viscid mucus production due to CF gene, cannot be cleared from lungs
  • Recurrent infections, bronchiectasis, and haemoptysis
  • Hyperinflation, pneumothorax, necrosis, scarring, pulmonary HT, and cor pulmonale