Pathology Summary Lesson 1 PDF

PATHOLOGY PROF. DR. A. KUBİLAY KORKUT, MD Define the Pathology Definitions : “patho” means disease, ”logy” means study from Greek The study of the structural, biochemical, and functional changes in cells tissues and organs that underlie disease. Aspects of the Disease Pathology explains...

PATHOLOGY PROF. DR. A. KUBİLAY KORKUT, MD Define the Pathology Definitions : “patho” means disease, ”logy” means study from Greek The study of the structural, biochemical, and functional changes in cells tissues and organs that underlie disease. Aspects of the Disease Pathology explains a disease by studying these 4 aspects: 1. Etiology (cause of the disease) 2. Pathogenesis (development of the disease) 3. Morphologic (structural) changes 4. Functional changes (dysfunction) and clinical significance Aspects of the Disease Etiology (causation or origination of the disease): There are 2 major etiologic factors Genetic Acquired (infectious, nutritional, chemical, etc.) If the cause is known, then called primary etiology If the cause is unknown, then called idiopathic Aspects of the Disease Pathogenesis : Pathogenesis are the mechanisms through which the cause operates the pathological and clinical manifestations Mechanisms could evident or latent (incubation period) Pathogenesis leads to morphologic changes Aspects of the Disease Morphologic changes : Morphological changes are the structural alterations in cells or tissues that occur following the pathogenetic mechanisms Can be seen with the naked eye (gross) or may only be seen under microscope (microscopic) Morphological changes lead to functional alteration, to the clinical signs, symptoms of the disease Aspects of the Disease Functional changes (dysfunction) and clinical significance : Morphologic changes influence the normal function of the organ Functional changes determine the clinical features (symptoms and signs), course, and the prognosis (outcome) of the disease Diagnostic Techniques in Pathology Histopathological Techniques Histopathological techniques study tissues under microscope Tissues for study are obtained by biopsy Biopsy is a tissue sample from a living person (usually anesthesia is required) Biopsy can be either incisional (partial) or excisional (total) Once the tissue is removed from the patient, it has to be immediately fixed* by 10% Formaldehyde solution *inactivating of microbes for long-time preservation of tissue Diagnostic Techniques in Pathology Cytopathologic Techniques (cyte = cell) Cytopathologic techniques study the cells from various body tissues. Applications of cytopathology 1. Screening for the early detection of asymptomatic cancer 2. Diagnosis of symptomatic cancer 3. Surveillance of patient treated for cancer Diagnostic Techniques in Pathology Cytopathologic Techniques Applications of cytopathology 1. Screening for the early detection of asymptomatic cancer For example, PAP smear screening test for early detection and prevention of cervical cancer (precancerous and normal cells). Diagnostic Techniques in Pathology Cytopathologic Techniques Applications of cytopathology 2. Diagnosis of symptomatic cancer Differential diagnosis of tumors revealed by physical or radiological examination (cyst ?, inflammatory condition ?, infection ?) Diagnostic Techniques Cytopathologic Techniques Applications of cytopathology 3. Surveillance of patient treated for cancer For example, periodic urine cytology to monitor the recurrence of cancer of the urinary tract Diagnostic Techniques in Pathology Cytopathologic Methods: 1. Fine-needle aspiration cytology (FNAC) 2. Exfoliative cytology 3. Abrasive cytology Diagnostic Techniques in Pathology Cytopathologic Methods: 1. Fine-needle aspiration cytology (FNAC) Cells are obtained by aspirating the diseased organ using a very thin needle under negative pressure with guidance by ultrasound, CT scan or fluoroscopy Superficial organs (e.g. thyroid, breast, lymph nodes, skin and soft tissues) Deep organs (e.g. lung, mediastinum, liver, pancreas, kidney, adrenal gland) Diagnostic Techniques in Pathology Cytopathologic Methods: 2. Exfoliative cytology Examination of cells that are shed spontaneously into body fluids or secretions e.g. sputum, cerebrospinal fluid, urine, effusions in body cavities (pleura, pericardium, peritoneum), nipple or vaginal discharge Diagnostic Techniques in Pathology Cytopathologic Methods: 3. Abrasive cytology Cells are dislodged by various tools from body surface (e.g. skin, mucous membranes, and serous membranes) Cervical smears preparation by spatula or small brush Diagnostic Techniques in Pathology Hematopathology Cells of the blood and their precursors in the bone marrow (e.g. anemia or leukemia) Immunohistochemistry To detect a specific antigen in the tissue (e.g. cancer cell antigen) Diagnostic Techniques in Pathology Microbiological examination To identify micro-organism (body fluids, excised tissue, etc. are examined by microscopical, cultural and serological techniques) Biochemical examination Investigation of the metabolic disease in the blood, urine, etc. Diagnostic Techniques in Pathology Cytogenetic test Chromosomal abnormalities (structure and number of chromosomes) are investigated using the techniques of molecular biology Molecular genetic test Molecular techniques (eg. fluorescent in situ hybridization) are used to detect genetic disease with studies segments (sequences) of DNA and specific genes at the molecular level. Diagnostic Techniques Autopsy Examination of the dead body to identify the cause of death for forensic or clinical purposes. The Causes of Disease Genetic factors Environmental factors Combination of the two The Causes of Disease Genetic factors The Causes of Disease Environmental factors 1. Physical agents 2. Chemicals 3. Nutritional deficiencies & excesses 4. Infections & infestations 5. Immunological factors 6. Psychogenic factors Outcome and Consequences of Disease 1. Resolution can occur leaving no sequelae 2. The disease can settle down, but sequelae are left 3. It may result in death Clinical & Biological Death Clinical death Reversible transmission between life and biologic death. Period of respiratory, circulatory and brain arrest during which initiation of resuscitation can lead to recovery. Clinical & Biological Death Signs indicating clinical death The patient is without pulse or blood pressure and is completely unresponsive to the most painful stimulus The pupils are widely dilated Some reflex reactions to external stimulation are preserved (for example, during intubation respiration may be restored) Recovery can occur with resuscitation (CPR) Clinical & Biological Death Signs indicating clinical death Recovery can occur with resuscitation (CPR) Clinical & Biological Death Biological death After clinical death, an irreversible state of cellular destruction Irreversible cessation of circulatory, respiratory and brain functions (including brain stem) Clinical & Biological Death Learning Objectives Define hyperplasia, hypertrophy, atrophy, metaplasia Define cell injury, etiology, pathogenesis Reversible and irreversible forms of cell injury The mechanism of necrosis The various types of necrosis and their causes Introduction When a cell is exposed to an injurious agent; the outcome depends on the type, severity and duration of the injury and the cell type The possible outcomes are; 1. The cell may adapt to the situation 2. The cell may acquire a reversible injury 3. The cell may obtain an irreversible injury and may die. The cell may die via two ways : either by necrosis or by apoptosis Types of cellular adaption 1. Hypertrophy 2. Hyperplasia 3. Atrophy 4. Metaplasia Types of cellular adaption Hypertrophy ; increase in the size of the cells Increase in cell size leads to increased size of the organ Example : the increase in skeletal muscle during exercise, or myocardial muscle hypertrophy because of hypertension Types of cellular adaption Hyperplasia ; increase in the number of the cells Increase in cell number leads to increased size of the organ Usually caused by hormonal stimulation Example : enlargement of the breast during pregnancy (physiological) or endometrial hyperplasia (pathological) Types of cellular adaption Atrophy ; decrease in the size of the cells Decrease in cell size leads to decreased size of the organ Cause (etiology) ; Disuse (lack of physical activity) Undernutrition Denervation (stroke, nerve injury) Aging Decreased endocrine stimulation Types of cellular adaption Metaplasia ; replacement of one differentiated tissue by another differentiated tissue Example ; the columnar epithelium of the bronchus can be replaced by squamous epithelium in cigarette smokers Types of cellular adaption Cell Injury and etiology Acquired causes ; Hypoxia and ischemia Physical agents Chemical agents and drugs Microbial agents Immunologic agents Nutritional derangements Aging Psychogenic disease Iatrogenic factors (originating from medical treatment) Idiopathic disease Cell Injury and etiology Hypoxia and ischemia ; The most common cause of cell injury Cells require oxygen to generate energy and perform metabolic function; decreased arterial concentration of oxygen (hypoxia) or insufficient blood flow to cells or organs (ischemia) results in failure to carry out these activities (pathogenesis). Cell Injury and etiology Hypoxia and ischemia ; Etiology of hypoxic cell injury The most common cause is reduced supply of blood to cells due to interruption (e.g. cerebral ischemia, myocardial ischemia) Disorders of oxygen-carrying red blood cells (e.g. anemia) Heart diseases, lung diseases, arterial system diseases Cell Injury and pathogenesis The cell may adapt to the situation The cell may acquire a reversible injury The cell may obtain an irreversible injury and may die. The cell may die via two ways : either by necrosis or by apoptosis Cell Death Cell death occur one of the following 2 ways ; 1. Necrosis 2. Apoptosis Necrosis Excess fluid enters the cell, swells the cell and ruptures its membrane After the cell died, intracellular degradative reactions occur within a living organism Necrosis does not occur in dead organism. In dead organism autolysis and heterolysis take place Types of Necrosis Coagulative necrosis Liquefactive necrosis Fat necrosis Caseous necrosis Gangrenous necrosis Types of Necrosis Coagulative necrosis ; Occurs by sudden interruption of blood supply to an organ, especially to the heart Types of Necrosis Liquefactive necrosis ; Characterized by digestion of tissue Softening and liquefaction of tissue e.g. Ischemic injury to the CNS Also occurs in suppurative infection characterized by formation of pus Types of Necrosis Fat necrosis ; Caused by trauma to tissue with high fat content, e.g. breast, acute hemorrhagic pancreatitis Types of Necrosis Caseous necrosis ; Has a cheese-like (caseous, white) appearance to the naked eye Typical of tuberculosis Types of Necrosis Gangrenous necrosis ; Due to vascular occlusion Most often affects the lower extremities and the bowel Wet gangrene : complicated by bacterial infection which leads to liquefactive necrosis Dry gangrene : there is only coagulative necrosis without liquefactive necrosis Apoptosis Death of single cells within cluster of other cells (necrosis causes the death of clusters of cells) The cells shows shrinkage and increased acidophilic staining of the cell This is followed by fragmentations of the cells (apoptotic bodies) Phagocytes remove apoptotic bodies. Apoptosis is not followed by inflammation or calcification (opposite of necrosis) Learning Objectives Define Inflammation Define acute and chronic inflammation Describe tissue responses to infectious agents Describe systemic effects and prognosis of acute inflammation Describe systemic effects of chronic inflammation Introduction Inflammation is the response of living mammalian tissues to injury due to any agent. The word inflammation means burning The agents causing inflammation may be as ; Infective agents (bacteria, viruses and their toxins, fungi, parasites) Immunological agents Physical agents (heat, cold, radiation, mechanical trauma) Chemical agents (organic and inorganic poisons) Inert materials (foreign bodies) Signs of Inflammation There are 5 cardinal signs of inflammation Rubor (redness) Tumor (swelling) Calor (heat) Dolor (pain) Functio laesa (loss of function) Signs of Inflammation Signs of Inflammation Types of Inflammation 1. Acute inflammation : short duration (less than two weeks), represents the early body reaction, usually followed by healing. The main features of acute inflammation; accumulation of fluid and plasma, intravascular activation of platelets 2. Chronic inflammation : longer duration The characteristic feature is presence of chronic inflammatory cells (lymphocytes, plasma cells, macrophages) and granulation tissue formation 3. Subacute inflammation : for the state of inflammation between acute and chronic Acute Inflammation 1. Vascular events Initial transient vasoconstriction Followed by massive vasodilation (redness and warm) Increased vascular permeability (fluid into the extracellular space – swelling) Blood flow slows (stasis) 2. Cellular events Leucocytic margination (mainly neutrophils) Cellular Events of Acute Inflammation Cellular events 1. Exudation of leucocytes : the most important feature of inflammatory response. 2. Phagocytosis : Cellular Events of Acute Inflammation Cellular events Exudation of leucocytes Phagocytosis : The process of engulfment of solid particulate material by the cells (cell-eating) Neutrophils and macrophages are phagocytic cells. Chemical Mediators of Acute Inflammation Chemical Mediators of Inflammation : They released from the cells, the plasma or damaged tissue, They increase vascular permeability, They cause vasodilation, fever, pain, chemotaxis and tissue damage. Morphology of Acute Inflammation Pseudomembranous Inflammation : Inflammatory response of mucous surface (oral, respiratory, bowel) Ulcer : Local defects on the surface of an organ produced by inflammation (stomach, duodenum, intestinal ulcers, various veins) Suppuration (abscess formation) : A cavity contains purulent exudate or pus. The bacteria which cause suppuration are called pyogenic. An abscess may be discharged to the surface due to increased pressure inside or may require drainage by the surgeon. Cellulitis : Diffuse inflammation of the soft tissues Bacterial infection of the blood : Bacteriaemia, septicaemia, pyaemia Morphology of Acute Inflammation Pseudomembranous Inflammation : Inflammatory response of mucous surface (oral cavity, respiratory system, bowel) Morphology of Acute Inflammation Ulcer : Local defects on the surface of an organ produced by inflammation (stomach, duodenum, intestinal ulcers, varicous veins) Morphology of Acute Inflammation Suppuration (abscess formation) : A cavity contains purulent exudate or pus. The bacteria which cause suppuration are called pyogenic. An abscess may be discharged to the surface due to increased pressure inside or may require drainage by the surgeon. Morphology of Acute Inflammation Cellulitis : Diffuse inflammation of the soft tissues Systemic Effects of Acute Inflammation Fever : occurs due bacteriaemia. Leukocytosis : (white blood cells) normally 4000-11000 /µL, during acute inflammation 15000-20000 / µL C-RP : elevated c-reactive protein (>10mg/dl) Lymphangitis – lymphadenitis : One of the important manifestation of localized inflammatory injury. Shock : may occur in severe cases. Massive release of mediators cause systemic vasodilation, systemic increased vascular permeability and intravascular volume loss, hypotension and shock, microthrombi, bleeding and death Fate (Prognosis) of Acute Inflammation 1. Resolution : It means complete return to normal tissue following acute inflammation. This occurs when tissue changes are slight, and the cellular changes are reversible (e.g. lobar pneumonia) 2. Healing by fibrosis : Tissue destruction is extensive, there is no tissue regeneration. But when tissue loss is superficial, its restored by regeneration with fibrotic scar tissue. Fate (Prognosis) of Acute Inflammation 3. Suppuration : When the pyogenic bacteria causing acute inflammation result in severe tissue necrosis, the process progresses to suppuration. Furthermore, in a cavity to form an abscess. The abscess should be drained spontaneously or with a surgical procedure. 4. Chronic inflammation : Persisting or recurrent acute inflammation may progress to chronic inflammation Chronic Inflammation Definition : prolonged process in which tissue destruction and inflammation occur at the same time. Caused by 3 different ways : Following acute inflammation (tissue destruction is extensive, or bacteria survive and persist in small number e.g. osteomyelitis, pneumonia terminating in lung abscess) Recurrent attacks of acute inflammation (e.g. in recurrent urinary tract infection leading to chronic pyelonephritis) Chronic inflammation starting de novo (without acute inflammatory response, with organisms of low pathogenicity e.g. mycobacterium tuberculosis) Systemic Effects of Chronic Inflammation Fever : mild fever, often with loss of weight and weakness Anemia : male : Hb < 13gr/dl, female: Hb < 12gr/dl Leukocytosis : white blood cell > 11000 /µL ESR : elevated in chronic inflammation C-RP : mild elevated c-reactive protein (>10mg/dl) Amyloidosis : This occurs when the body produces a protein called serum amyloid A because of inflammation or infection. Learning Objectives Define arteries, types of the arteries Define histological layers of the arteries Describe disease of the arteries Define Arteriosclerosis and morphological entities Define Atherosclerosis, risk factors, pathogenesis Define clinical effects of atherosclerosis Define arteritis Define aneurysms Arteries There are 3 types of arteries depending upon the caliber 1. Large (elastic) arteries (Aorta and major branches) 2. Medium-sized (muscular) arteries (Visceral arteries and branches) 3. Smallest arterioles (Arterioles, capillaries) Arteries Histologically all the arteries have 3 layers 1. Tunica intima (lining Endothelium, smooth surface for blood flow) 2. Tunica media (consists mainly smooth muscle cells) 3. Tunica adventitia (Outer coat) Diseases of the Arteries 1. Arteriosclerosis 2. Arteritis (Vasculitis) 3. Aneurysms Arteriosclerosis Arteriosclerosis is thickening and hardening of the arterial walls. There are 4 morphologic entities are included under arteriosclerosis 1. Senile arteriosclerosis (due to aging) 2. Hypertensive arteriosclerosis 3. Mönckeberg’s Arteriosclerosis (Medial Calcific Sclerosis) (calcification of the media, age-related degenerative process) 4. Atherosclerosis Atherosclerosis Atherosclerosis is the most common and important of the inflammatory arterial diseases. The disease affecting primarily the intima and is characterized by fibrofatty plaques or atheromas. Risk Factors in Atherosclerosis 1. Major Risk Factors A. Constitutional (non-modifiable) 1. Age (increasing age) 2. Sex (male) 3. Genetic factors (genetic abnormalities) 4. Familial and racial factors B. Modifiable (controlled modifying by life style and/or therapy) 1. Smoking 2. Hypertension 3. Diabetes mellitus 4. Dyslipidemia Pathogenesis of Atherosclerosis 1. Endothelial injury (the initial triggering event in the development of lesions in atherosclerosis. 2. Platelet adhesion and monocyte migration 3. Intimal smooth muscle cell proliferation Morphologic Features of Atherosclerosis 1. Fatty Streaks and Dots 2. Intermediate Lesion 3. Atheroma 4. Fibrous Plaque 5. Complicated Lesion/Rupture a. Calcification b. Ulceration c. Thrombosis d. Hemorrhage e. Aneurysm Formation Clinical Effects of Atherosclerosis Clinical effects of atherosclerosis depend upon the size and type of arteries affected. 1. Slow luminal narrowing causing ischemia and atrophy 2. Sudden luminal occlusion causing infarction and necrosis 3. Thrombi and emboli formation from the plaque 4. Formation of aneurysmal dilatation and rupture Clinical Effects of Atherosclerosis Major sites of atherosclerosis in order of frequency 1. Abdominal aorta and iliac arteries 2. Coronary arteries 3. Internal carotid arteries 4. Cerebral artery 5. Thoracic aorta Diseases of the Arteries 1. Arteriosclerosis 2. Arteritis (Vasculitis) 3. Aneurysms Arteritis Arteritis, angiitis, vasculitis are the common terms used for inflammatory process in an artery or an arteriole. Classification of Vasculitis; 1. Infectious Arteritis (less common) Endarteritis obliterans Non-syphilitic infective arteritis Syphilitic arteritis Arteritis 2. Non-infectious Arteritis (most of the vasculitis forms) (exact etiology is not known, many of them have immunologic origin) Polyarteritis nodosa (PAN) Hypersensitivity (allergic, leucocytoclastic) vasculitis Wegener’s granulomatosis Temporal (giant cell) arteritis Takayasu’s arteritis (pulseless disease) Kawasaki’s disease Buerger’s disease (thromboangiitis obliterans) Miscellaneous vasculitis Arteritis Buerger’s disease (thromboangiitis obliterans) The disease affects chiefly men under the age of 35 years who are heavy cigarette smokers. Gangrene of the affected extremities occurs requiring amputation Diseases of the Arteries 1. Arteriosclerosis 2. Arteritis (Vasculitis) 3. Aneurysms Aneurysm Aneurysm is abnormal dilatation of a blood vessel occurring congenital or acquired weakening or destruction of the vessel. Most commonly, aneurysms involve especially the aorta and its major branches. Aneurysms can cause thrombosis, thromboembolism, rupture of the vessel and compression of neighboring structures. Aneurysm Classification A. Depending upon the composition of the wall 1. True aneurysm (composed all the layers) 2. False aneurysm (Pseudo-aneurysm) (hematoma outside of the artery following injury) Learning Objectives Define normal structure of the heart Define ischemic heart disease Define Rheumatic Fever and Rheumatic Heart Disease Define valvular disease Anatomy and Physiology of the Heart There are 2 atrio-ventricular valves; Mitral (left), Tricuspid (right) There are 2 semilunar valves Aortic (left), Pulmonary (right) Anatomy and Physiology of the Heart The heart wall has 3 layers; Pericardium (outermost layer, Parietal and Visceral epicardium, surrounds and protect the heart) Myocardium (heart muscles, contraction and relaxation action) Endocardium (innermost layer, lines inner chamber, provides smooth surface) Ischemic Heart Disease (IHD) IHD is defined of cardiac disability from imbalance between myocardial supply and demand for oxygenated blood. IHD has acute or chronic form. Since the most common cause is narrowing or obstruction of the coronary arterial system, coronary artery disease (CAD) is used synonymously with IHD. Ischemic Heart Disease - Etiopathogenesis Atherosclerosis is the cause for more than 90% cases Coronary atherosclerosis Superadded changes in coronary atherosclerosis (hemorrhage, ulceration that results thrombosis and embolism) Non-atherosclerotic causes (Vasospasm, arteritis, aneurysm) Ischemic Heart Disease – Clinical features Depending upon the suddenness of onset, duration, degree, location, extent of the area affected by myocardial ischemia 1. Asymptomatic state 2. Angina pectoris (AP) 3. Acute myocardial infarction (AMI) 4. Chronic ischemic heart disease (CIHD) 5. Sudden cardiac death Rheumatic Fever and Rheumatic Heart Disease Rheumatic fever (RF) is a systemic, post-streptococcal, non- suppurative inflammatory disease. RF is affecting the heart, joints, central nervous system, skin and subcutaneous tissues. RF is more commonly seen in poor socioeconomic countries. Rheumatic Heart Disease - Morphologic Features Rheumatic endocarditis (valvular involvement) Rheumatic myocarditis Rheumatic pericarditis VALVULAR DISEASES There are 3 types of valvular disease ; 1. Stenosis : Failure of a valve to open completely during diastole (mitral or tricuspid) or during systole (aortic or pulmonary) resulting in obstruction to the forward flow of the blood 2. Insufficiency or incompetence or regurgitation : Failure of a valve to close completely during systole (mitral or tricuspid) or during diastole (aortic or pulmonary) resulting in back flow or regurgitation of the blood 3. Mixt (Stenosis and regurgitation together) VALVULAR DISEASES Mitral Stenosis RHD is the cause 40%of all patients, more often in women 70%. Bacterial endocarditis, endocardial fibroelastosis and congenital parachute mitral valve are the other etiologies. VALVULAR DISEASES The Effects of Mitral Stenosis ; 1. Dilatation and hypertrophy of the left atrium 2. Normal-sized or atrophic left ventricle due to reduced inflow of blood 3. Pulmonary hypertension  VALVULAR DISEASES Mitral Insufficiency ; RHD is the cause 50%of all patients, more often in men 75%. Calcification of the mitral valve annulus (in the elderly), myxomatous transformation of the mitral valve, rupture of a leaflet or of the chordae tendinea or of a papillary muscle, dilatation of the mitral ring (in MI), left ventricular failure in hypertension Mitral insufficiency is associated with some degree of mitral stenosis. VALVULAR DISEASES Aortic Stenosis More often in men 80%. 2 main types ; 1. Calcific aortic stenosis (more common type) : etiologies are senile (old age), RHD, bacterial endocarditis, Monckeberg’s calcific aortic stenosis, familial hypercholesterolemic xanthomatosis. 2. Non-calcific aortic stenosis : etiologies are RHD, congenital valvular stenosis, congenital bicuspid aorta VALVULAR DISEASES Aortic Stenosis 1. Calcific aortic stenosis 2. Non-calcific aortic stenosis VALVULAR DISEASES Effects of Aortic Stenosis ; Aortic stenosis becomes symptomatic when the valve orifice is reduced to 1cm2 (norm: 3cm2). Obstruction to the outflow resulting in concentric hypertrophy of the left ventricle. Three cardinal symptoms ; 1. Exertional dyspnea (due to elevation of pulmonary capillary pressure) 2. Angina pectoris (due to increased demand of hypertrophied myocardial mass) 3. Syncope (results from accompanying coronary insufficiency) Sudden death may also occur in an occasional case of artic stenosis VALVULAR DISEASES Aortic Insufficiency About three-fourth of all patients are males with history of Marfan’s syndrome Etiology RHD in 75% of patients (usually other valves are involved as well at the same time) Congenital subaortic stenosis Dissecting aneurysm Marfan’s syndrome Learning Objectives Define normal structure of the respiratory system Define disease of the respiratory system Define pediatric lung diseases Define neonatal and adult acute respiratory distress syndrome Define atelectasis and collapse Define pulmonary vascular disease Define pulmonary infections Define chronic obstructive pulmonary disease Define chronic restrictive pulmonary disease Define tumors of the lungs Respiratory System Respiration : Responsible for the exchange of gases between the body and the air Provides oxygen to the body cells for energy and removes carbon dioxide (a waste product of cellular metabolism) Respiratory System There are 2 different processes: 1. External respiration : Oxygen and carbon dioxide exchange through the capillaries of the lung 2. Internal respiration : At the cellular level, the oxygen passes through the capillaries into the individual tissue cells, carbon dioxide from the cell through the capillaries into the bloodstream Diseases of the Respiratory System 1. Pediatric lung disease 2. Pulmonary vascular disease 3. Pulmonary infections 4. Chronic obstructive pulmonary disease 5. Chronic restrictive pulmonary disease 6. Tumors of the lungs Pediatric Lung Disease Congenital anomalies : Agenesis, hypoplasia, heterotopic tissue, vascular anomalies, tracheal and bronchial anomalies, congenital pulmonary overinflation or lobar emphysema, congenital cysts, bronchopulmonary sequestration) Neonatal acquired lung disease : (respiratory distress syndrome or hyaline membrane disease, bronchopulmonary dysplasia, meconium aspiration syndrome, persistent fetal circulation, atelectasis, collapse, bronchiolitis) Acute Respiratory Distress Syndrome (ARDS) (Hyaline Membrane Disease) ARDS exists in 2 forms : Neonatal and Adult There is insufficiency of pulmonary surfactant production and structural immaturity of the lungs Pathogenesis : Formation of hyaline membrane in the alveoli Neonatal Acute Respiratory Distress Syndrome (ARDS) (Hyaline Membrane Disease) Atelectasis ; total or partial collapse of the lung, results in hypoventilation, pulmonary hypoperfusion and ischemic damage to capillary endothelium. This result ischemic necrosis, exudation of plasma proteins and formation of hyaline membrane in the alveoli. Adult (ARDS) (Hyaline Membrane Disease) Imbalance between pro-inflammatory and anti-inflammatory cytokines. Injury to the capillary endothelium and alveolar epithelium leads intra- alveolar edema, congestion and formation of hyaline membrane. Causes : Shock due sepsis, trauma, burns, Diffuse pulmonary infections (mostly viral pneumonia) Aspiration pneumonitis Inhalations of toxins and irritants (smoke) Narcotic overdose Pancreatitis Atelectasis and Collapse Primary atelectasis ; incomplete expansion of the lung or part of the lung. They have weak respiratory action. Common causes are prematurity, cerebral birth injury.  Atelectasis and Collapse Secondary atelectasis (pulmonary collapse) ; reduction in lung size of a previously expanded and well-aerated lung. Compressive collapse : massive pleural effusion (hemothorax, pneumothorax, intrathoracic tumor, high diaphragm) Obstructive/absorptive/resorptive collapse : obstruction of the bronchus (bronchial asthma, chronic bronchitis, bronchiectasis, bronchial tumors, aspiration of foreign bodies) Contraction collapse : due to localized fibrosis of the lung Diseases of the Respiratory System 1. Pediatric lung disease 2. Pulmonary vascular disease 3. Pulmonary infections 4. Chronic obstructive pulmonary disease 5. Chronic restrictive pulmonary disease 6. Tumors of the lungs  Pulmonary Vascular Disease Pulmonary Hypertension (PH) Pulmonary arterial circulation is a high-flow and low-pressure system. Pulmonary arterial blood pressure does not exceed 30/15 mmHg. PH is defined as a systolic arterial blood pressure in pulmonary circulation above 30 mmHg. Pulmonary Vascular Disease Primary (Idiopathic) Pulmonary Hypertension (PH) The cause is unknown, patients are usually female between the age of 20-40 years, or children around 5 years old. There is a suggestion that its may be a form of collagen vascular disease. Pulmonary Vascular Disease Secondary Pulmonary Hypertension (PH) It is more common type, more frequently over the age of 50 years old. Etiopathogenesis : Mitral stenosis, Atrial or Ventricular Septal Defect, Patent ductus arteriosus Pulmonary embolism or thrombi Diseases of the Respiratory System 1. Pediatric lung disease 2. Pulmonary vascular disease 3. Pulmonary infections 4. Chronic obstructive pulmonary disease 5. Chronic restrictive pulmonary disease 6. Tumors of the lungs Pulmonary Infections Acute infections : Pneumonia, Lung abscess, Fungal infections Chronic infections : Pulmonary tuberculosis  Pneumonia Pneumonia is defined acute inflammation of the lung parenchyma. Entryways into the lungs ; inhalation, aspiration, hematogenous spread, direct spread from an adjoining site. Classification of Pneumonia A. On the basis of the anatomic part of the lung parenchyma involved; 1. Lobar pneumonia 2. Bronchopneumonia (or Lobular pneumonia) 3. Interstitial pneumonia B. Etiologic classification 1. Bacterial pneumonia 2. Viral pneumonia 3. Pneumonias from other etiologies Classification of Pneumonia A. On the basis of the anatomic part of the lung parenchyma involved; Lobar pneumonia Classification of Pneumonia A. On the basis of the anatomic part of the lung parenchyma involved; Bronchopneumonia (or Lobular pneumonia) Classification of Pneumonia A. On the basis of the anatomic part of the lung parenchyma involved; Interstitial pneumonia Etiologic Classification of Pneumonia A. Bacterial Pneumania 1. Lobar pneumonia 2. Bronchopneumonia (Lobular pneumonia) B. Viral and Mycoplasmal Pneumonia (primary atypical pneumonia) C. Other types of pneumonia 1. Pneumocystis carinii pneumonia 2. Legionella pneumonia 3. Aspiration (inhalation) pneumonia 4. Hypostatic pneumonia 5. Lipid pneumonia Bacterial Pneumonia The most common cause of pneumonia Lobar pneumonia : acute bacterial infection of a part of a lobe or even two lobes of one or both the lungs. Etiology 1. Pneumococcal pneumonia : more than 90% of all lobar pneumonias are caused by Streptococcus pneumoniae 2. Staphylococcal pneumonia : Staphylococcus aureus 3. Streptococcal pneumonia : B-haemolytic streptococci 4. Pneumonia by gram-negative aerobic bacteria : less common cause Heamophilus influenzae, Klebsiella pneumonia, Pseudomonas Morphologic Features Lobar pneumonia divides into 4 sequential pathologic phases 1. Stage of Congestion (Initial phase) : early acute inflammatory response to bacterial infection, lasts 1-2 days. Lobe is enlarged, dared and congested. Dilatation and congestion of the capillaries in the alveolar wall. A few red cells and neutrophils and numerous bacterias in the antra-alveolar fluid. Morphologic Features Lobar pneumonia divides into 4 sequential pathologic phases 2. Red Hepatisation (Early Consolidation) : lasts for 2 to 4 day, liver-like consistency of affected lobe. Lobe is red, consolidated. There is serofibrinous pleuristy. There is marked cellular exudate of neutrophils and extravasation of red cells. Morphologic Features Lobar pneumonia divides into 4 sequential pathologic phases 3. Grey Hepatisation (Late Consolitadion): lasts for 4 to 8 day, liver-like consistency of affected lobe. Colour changes from red to grey. Fibrinous pleurisity is prominent. Neutrophils, red cells, the organism are less and macrophages appears in exudate. Morphologic Features Lobar pneumonia divides into 4 sequential pathologic phases 4. Resolution: begins by 8th to 9th day, completed in 1-3 weeks. Antibiotics induces resolution phase on 3rd day. Normal aeration is restored. Pleural reaction shows resolution. Macrophages are predominant cells. Complications 1 1. Organisation : In 3% of cases, failure of resolution, intra-alveolar scarring (fibrosis) (carnification) cause permanent loss of ventilatory function of the affected lobe. 2. Pleural effusion : In 5% of treated cases, pleural effusion with fibrous adhesions may develop between the two pleural membrane. Complications 2 3. Empyema : In less than 1% of treated cases may develop pus in pleural cavity termed empyema. 4. Lung abscess : A rare complication, especially when there is secondary infection by other organism. 5. Metastatic infection : Very rare, infection extends pericardium and heart, purulent pericarditis, myocarditis, endocarditis. Bacterial Pneumonia Bronchopneumonia (Lobular Pneumonia) : infection of the terminal bronchioles and alveoli, more common in infancy and old age Etiology : Staphylococci, Streptococci, Pneumococci, Klebsiella pneumoniae, Haemophilus influenzae, Pseudomonas Morphologic Features : patchy areas of red or grey, 3 to 4 cm in diameter centered around a bronchiole. Bacterial Pneumonia Bronchopneumonia (Lobular Pneumonia) Complications : All the same complications in lobar pneumonia. Complete resolution of bronchopneumonia is uncommon. Destruction of bronchioles may cause bronchiectasis. Lung Abscess Lung Abscess is a localized area of necrosis of lung tissue with suppuration. Etiopathogenesis : Streptococci, Staphylococci, gram negative organisms 1. Aspiration of infected foreign material 2. Preceding bacterial infection 3. Bronchial obstruction 4. Septic embolism 5. Miscellaneous (pulmonary infarct, trauma, etc.) Chronic Obstructive Pulmonary Disease (COPD) Chronic disfunction of the lungs with partial or complete obstruction of the airflow. There are 4 entities in COPD : 1. Chronic bronchitis 2. Emphysema 3. Bronchial asthma 4. Bronchiectasis Chronic Obstructive Pulmonary Disease (COPD) Chronic bronchitis : Defined clinically as persistent cough with expectoration for at least three months of the year for two or more consecutive years. More common in middle-aged men. Etiologic factors : smoking, atmospheric pollution, occupation, infection, familial and genetic Morphologic features : Bronchial wall is thickened, hyperaemic, edematous, there are mucus plaques and purulent exudate Chronic Obstructive Pulmonary Disease (COPD) Emphysema : Defined morphologically as permanent dilatation of air spaces distal to the terminal bronchioles and the destruction of the walls of dilated air spaces. Etiopathogenesis : Smoking, air pollution, occupational, familial and genetic factors  Chronic Obstructive Pulmonary Disease (COPD) Bronchial Asthma : Defined as increased responsiveness of the tracheobronchial tree resulting spasmodic narrowing of the air passage. Etiopathogenesis : 1. Extrinsic (allergic, atopic) : The most common type, personal or family history, hypersensitivity to various extrinsic antigenic ‘allergens (house dust, pollens, etc.)’ 2. Intrinsic (non-atopic) : mostly develop after an upper respiratory tract infection by viruses, associated nasal polypi and chronic bronchitis are common. 3. Mixt type Chronic Obstructive Pulmonary Disease (COPD) Bronchiectasis : Defined as abnormal and irreversible dilatation of the bronchi and bronchioles. Chronic Obstructive Pulmonary Disease (COPD) Bronchiectasis : Etiopathogenesis : 1. Hereditary and congenital factors 2. Endobronchial obstruction (foreign body, neoplastic growth, enlarged lymph nodes) 3. Infection Clinical Features : Chronic cough with foul-smelling sputum, hemoptysis, recurrent pneumonia Chronic Restrictive Pulmonary Disease (CRPD) Defined as reduced expansion of lung parenchyma with decreased total lung capacity. 1. Restriction due to chest wall disorders a. Kyphoscoliosis b. Poliomyelitis c. Severe obesity d. Pleural disease Chronic Restrictive Pulmonary Disease (CRPD) 2. Restriction due to interstitial and infiltrative disease (interstitial lung disease) Pneumoconiosis : inhalation of dust, mostly at work, (coal dust, silica, asbestos) Idiopathic pulmonary fibrosis : most common form with bad prognosis Connective tissue diseases : scleroderma, rheumatic arthritis sarcoidosis Tumors of the Lungs A number of benign and malign tumors occurs in the lungs. Primary lung cancer (bronchogenic carcinoma) is the most common (95% of all primary lung tumors) The lung is also the commonest site for metastasis (secondary) Bronchogenic carcinoma Etiology : 1. Smoking : 80% of the lung cancer occurs in active smokers 2. Other factors : Atmospheric pollution, occupational causes, dietary factors (Vit A deficiency), chronic scarring (tuberculosis, asbestosis, chronic interstitial fibrosis) Bronchogenic carcinoma Histologic types : 1. Squamous cell (epidermoid cell) 2. Adenocarcinoma 3. Large cell carcinoma 4. Small cell carcinoma 5. Combined squamous cell and adenocarcinoma (adenosquamous) Therapeutic purposes types : 1. Small cell carcinoma (20-25%) 2. Non-small cell carcinoma (70-75%) 3. Combined/mixed (5-10%) Metastatic Lung Tumors Secondary tumors of the lung are more common than primary tumors. Blood-borne metastases are the most common. Most common sources are carcinomas of the bowel, breast, thyroid, kidney, pancreas, liver, ipsilateral or contralateral lung