Infectious Diseases INFECTION • Definition: • Invasion of the body by pathogens and the development of pathological changes. Mode of Infection Exogenous infection: • From the environment, a patient or a carrier. • The routes of exogenous infection are: • (a) Skin and mucous membrane! contact, • (b) Inhalation, • (c) Ingestion. • Endogenous infection: • By pathogenic bacteria normally present in the body as streptococcus viridans in the mouth, pneumococci in the nasopharynx and E. coli in the intestine. • Infection occurs when the defensive mechanisms of the body are overcome. Host Barriers to Infection • The outcome of infection is determined by the ability of the microbe to infect, colonize, and damage host tissues and the ability of host defense mechanisms to eradicate the infection. • Host barriers to infection prevent microbes from entering the body and consist of : • Innate immune defense mechanisms . • Adaptive immune responses Effects of Infection: • Inflammation. • Toxaemia. • Blood invasion by bacteria (bacteraemia, septicaemia and pyaemia). • Immunity and hypersensitivity. TOXAEMIA • Definition: Circulation of bacterial toxins in the blood causing pathological and clinical manifestations. Bacterial toxins are of two types: • Exotoxins: Produced by gram positive bacteria as diphtheria bacilli and some types of streptococci. • Endotoxins: Released from the bodies of dead gram negative bacteria as typhoid bacilli. • Types: • Acute toxaemia: Occurs in acute infections as diphtheria. • Chronic toxaemia: Occurs in chronic infections as tuberculosis. TOXAEMIA • Manifestations of Toxaemia: • Constitutional signs and symptoms: Fever, rigor, headache, weakness and increased rate of tissue metabolism. • Degeneration: Mainly in the heart, kidney and liver in the form of cell swelling and fatty change. Severe toxaemia causes acute heart failure. Chronic toxaemia may cause amyloidosis. • Necrosis and haemorrhage of the adrenal cortex: May be fatal due to acute adrenal cortical insufficiency. • Anaemia: Due to bone marrow depression by the toxins. BACTERAEMIA • Definition: • Transient presence of small number of bacteria in the blood stream without toxic manifestations. • Pathogenesis: Bacteria enter the blood stream from a septic focus in the body e.g. tonsillitis, sinusitis, cholecystitis, salpingitis ... etc. • A common example of bacteraemia is that occurring after tooth extraction. SEPTICAEMIA • Definition: • The circulation and multiplication of large number of virulent bacteria and their toxins in the blood stream. The condition is highly fatal. • Causative organisms: • The commonest is streptococcus haemolyticus. • Sources: Important sources are infected, septic wounds, puerperal sepsis and acute osteomyelitis. SEPTICAEMIA Pathology of Streptococcus Haemolyticus Septicaemia: (1) Red cell haemolysis by haemolysin causing anaemia and red staining of the intima of the vessels by the liberated haemoglobin (2) Petechial haemorrhage in the skin, mucous and serous membranes due to capillary destruction by the streptococcal toxins (3) Cloudy swelling, fatty change and focal necrosis in the heart, liver and kidney (4) Serofibrinous or suppurative inflammation in the serous sacs (5) Acute splenic swelling PYAEMIA • Definition: Pyaemia is the circulation of septic emboli in the blood. Pyaemia has a high mortality rate. • Pathogenesis: When a septic focus involves a vein, fragments from the septic thrombus circulate in the blood stream as septic emboli. • Next the septic emboli get impacted in the small vessels of different organs producing multiple small pyaemic abscesses. PYAEMIA • Types: 1) Systemic pyaemia: The septic emboli circulate in the systemic venous blood. They are derived from acute osteomyelitis, puerperal sepsis, suppurative otitis media, cellulitis and acute bacterial endocarditis. They get arrested in the lung forming multiple pyaemic abscesses. Smaller emboli from the lung reach the kidney, liver, brain ... etc. 2) Portal pyaemia: The septic emboli circulate in the portal venous blood. They are derived from acute suppurative appendicitis, infected piles, acute cholecystitis, diverticulitis and septic lesions in the colon. The emboli get arrested in the liver forming multiple pyaemic abscesses Bacterial, Fungal & Parasitic Infection Tuberculosis Syphilis Leprosy Actinomycosis Mycetoma Schistosomiasis TUBERCULOSIS Definition: Chronic infective granuloma caused by tubercle bacilli Causative organism: • Two types of bacilli infect man: Human and Bovine • Its growth is strict aerobic and inhibited by acidic ph • It has no known exotoxins, endotoxins or histolytic enzymes • It consists of complex lipid, carbohydrate around tuberculoprotein • The bacteria is non-motile and are carried by macrophages to spread by various methods TUBERCULOSIS Methods of infection: • Inhalation: is the commonest method • The human bacilli are inhaled in coughed droplets or dust contaminated with sputum from a case with opened TB • The inhaled bacilli infect the tonsils or the lung • Most infections are acquired by sustained exposure rather than casual contact • Ingestion: of raw milk contaminated with bovine or human bacilli. They infect the tonsils or intestine • Skin inoculation: by handling infected material. This method is not common PATHOGENESIS • The pathogenesis of tuberculosis in the previously unexposed immunocompetent individual is centred on the development of cellmediated immunity associated with tissue hypersensitivity to tubercular antigens • The pathologic features of tuberculosis, such as caseating granulomas and cavitation, are the result of the destructive tissue hypersensitivity PATHOGENESIS • The sequence of events from inhalation of bacteria to formation of the primary focus is as follow: • The earliest phase of primary tuberculosis (<3 weeks) in the nonsensitized individual is characterized by unchecked bacillary proliferation within the pulmonary alveolar macrophages and airspaces, with resulting bacteremia and seeding of multiple sites • • The development of cell-mediated immunity occurs (> 3 weeks after exposure. Processed mycobacterial antigens are presented to T lymphocytes, resulting in macrophage activation, monocytes recruitment & granuloma formation PATHOGENESIS TISSUE REACTION IN TUBERCULOSIS I - Proliferative tissue reaction Composed mainly of inflammatory cells II – Exudative tissue reaction Having excess inflammatory fluid exudate TUBERCLE Definition: • Is the unit of proliferative tissue reaction • Composed of a compact collection of Epithelioid cells Langhan’s giant cells Lymphocytes Microscopic Picture of Tubercles 1-Epithelioid cells: With abundant pale red cytoplasm, indistinct cell borders and round or oval vesicular nuclei 2- Langhan’s giant cells 3- Lymphocytes 4- Central caseation TB bacilli inside epithelioid cells Tuberculosis Clinical patterns • Primary type: occurring in individuals following the initial infection, this type is called childhood type, as it is frequent in children leading to formation of primary complex • Post primary (secondary type): tend to be more chronic and slowly progressive. It is associated with significant (although inadequate) resistance Primary Tuberculosis Primary complex Sites: • Tonsil • Lung • Intestine • Skin Primary Pulmonary Complex • Ghon’s Focus Under the pleura, small in size (1cm) with late caseation • Tuberculous lymphangitis • Tuberculous lymphadenitis Fate of Primary Complex I- Healing - Fibrosis & calcification - Very small foci - Bacilli may persist for life II- Spread: low immunity 1- Direct: focus enlarges and gives new lesions with extensive caseation 2- Haematogenous Small No of bacilli Moderate number of bacilli Large number of bacilli Miliary TB 3- Bronchial spread III- Encapsulation and reactivation Secondary Tuberculosis • This type of tuberculosis arises in a previously sensitized individual, whether the TB bacilli are derived from endogenous or exogenous sources • Most cases of secondary TB represent reactivation of asymptomatic primary disease • The reactivation is the result of shift in the balance between host and organism due to such factors as reduced immunity, poor nutritional status, alcoholism or advanced age Secondary Pulmonary Tuberculosis Apical lesion • Are almost always near the apex of the lung at sites of high oxygen tension (where the bacilli had localized at the time of original bacillemia) • The minimal lesion at the apex consists of 1-3 cm focal area of caseous consolidation, usually within 1 -2cm from pleural surface TB cavities with caseation Secondary Pulmonary Tuberculosis Course of Apical lesion a) Healing, scarring and calcification giving fibrocalcific 'arrested‘ tuberculosis b) Progressive local spread: Fibrocaseous foci may undergo softening and erode through airways and emptying of this soft material into the bronchus (open case) leaving a cavity lined by caseous material and surrounded by fibrous tissue (Chronic fibrocaseous T.B) Retrograde spread of caseous material through the distal airways produce small caseating (acinar lesions) mainly at the base of the lung. These lesions subsequently fuse into larger lesion Chronic firocaseous TB Secondary Pulmonary Tuberculosis Course of Apical lesion c) Tuberculous pneumonia: In the highly susceptible, highly sensitized individual, the tuberculous infection may spread rapidly throughout large areas of lung parenchyma and produce a diffuse bronchopneumonia, or lobar exudative consolidation d) Further local contiguous dissemination: – To the pleural space (tuberculous empyema) or, – Spread along contiguous passages (tracheobronchial) to the larynx - then to intesine Isolated Organ Tuberculosis • Reactivation of bacilli that had widely distributed at the time of bacteraemia, but undergoes proliferation in only one area, meninges, kidney, adrenal, cervical lymph nodes, bone with subsequent local extension ((eg.. TB nephritis —> cystitis and salpingitis or epididymitis) Pott’s disease Miliary Tuberculosis • With very low body resistance lesions may spread into lymphatics and blood vessels—-> then wide dissemination • The distribution of miliary lesions depends on the pathways of dissemination • Favored targets for miliary seeding are the bone marrow, liver, spleen, and retina Miliary tuberculosis Miliary tuberculosis Schistomiasis Schistomiasis ( Bilharziases) Definition Chronic granuloma caused by schistosomal infection Three species are present: 1.Schistosoma Haematobium 2.Schistosoma Mansoni 3.Schistosoma Japonicum Life Cycle of Schistomiasis Schistosomal Lesions • Cercaria: Cause acute dermatitis • Adult worms: o Living worms: ingest blood and excrete brown bilharzial pigment o Dead worms: cause severe allergic inflammation with necrosis and eosinophilic infiltrate Schistosomal Lesions • Ova: Produce granulomatous reaction formed of: • • • • • • Macrophages Lymphocytes Plasma cells Eosinophils Few giant cells Fresh or calcified bilharzial ova Intestinal Bilharziasis • • Pathological features Mild Infection: Petechial haemorrhage, Bilharzial granulomas in submucosa • Severe prolonged infection: In addition to bilharzial granulomas the following lesions develop 1. Sandy patches 2. Bilharzial ulcer 3. Bilharzial polyps Bilharzial polyp Multiple bilharzial polyps Bilharziasis of the Liver • Common disease, secondary to closed intestinal bilharziasis • Emboli of the ova and dead worms reach the liver by portal blood • Types: 1. Fine B portal fibrosis 2. Coarse B portal fibrosis 3. Mixed type • Complications Portal hypertension Effects: 1. Splenomegaly 2. Opening of porto-systemic anastomosis Oesophageal varices Piles Caput medusa 3. Ascites Complication of Portal hypertension Oesophageal varices Splenomegaly Ascites Caput Medusae Urinary Bladder Bilharziasis • Pathological Features: 1- Sandy patches 2- Bilharzial polyps 3- Bilharzial ulcers 4- Epithelial changes a- Hyperplasia b- Brunn’s nests c- Cystitis cystica d- Cystitis glandularis e- Squamous metaplasia Actinomycosis ACTINOMYCOSIS • Chronic infective suppurative granuloma caused by an anaerobic Gram-positive bacterium “actinomyces Israel”. • The infection may be endogenous as the organism is a normal saprophyte of the mouth, tonsils, carious teeth and intestinal tract • Previously thought to be a fungal infection, but these organisms are actually gram-positive, filamentous bacteria ACTINOMYCOSIS • Actinomycosis is a chronic disease characterized by the production of suppurative abscesses or granulomas that eventually develop draining sinuses. • These lesions discharge pus containing the organisms. • The organisms are found in firm, yellowish granules called sulfur granule ACTINOMYCOSIS • The disease is divided into three major clinical types: 1.Cervicofacial 2.Thoracic 3.Abdominal • But primary infections may involve almost any organ. Cervicofascial Actinomycosis Mycetoma Pedis Mycetoma Pedis ( Nocardiosis) Chronic infective suppurative granuloma, affects mainly the foot, caused by free living saprophytes called Nocardia Pathological features Gross: Multiple sinuses discharging pus containing the fungal colonies Madura foot ( Mycetoma) Syphilis Syphilis • Definition: Infective granuloma caused by a spirochete called Tropenema pallidum Mode of Mode of Infection: 1. Direct contact of the body with a source of infection, commonly during sexual intercourse. The spirochaetes can penetrate the intact skin or mucous membrane. 2. Congenital infection of the foetus from the mother through the placenta Syphilis Lesions in Syphilis Primary Stage: Chancre Secondary stage: Tertiary stage: Skin rash Gumma Mucous patches Condyloma latum Generalized lymphadenopathy Diffuse syphilitic reaction Tissue Reaction in Syphilis Chronic inflammatory reaction formed of Perivascular infiltrate of: • Plasma cells • Lymphocytes • Few small giant cells • Blood vessels show endarteritis obliterans • II. Secondary Stage: (2) Mucous Patches: Occur in the mouth, pharynx, vagina, cervix and anal canal. They are round or oval slightly raised above the surface, covered by whitish or greyish membrane and surrounded by a red border Some of these lesions may ulcerate. The resulting small ulcers may coalesce together and form a snail tract ulcer. (3) Generalized lymphadenitis: Specially the epitrochlear and posterior cervical. Microscopically their changes are the same as the node draining the primary stage. Splenic enlargement Mucous patches Alopecia III. Tertiary Stage: • Secondary lesions also heal spontaneously and the disease pass into a latent phase that may extend for years (2-10 years) until tertiary lesions develop which are of two types: (l)Gumma: Localized area of syphilitic granulation tissue which undergoes slow caseation necrosis. Gumma affects any organ, but the common sites are the liver, meninges, bone, tongue, testis, heart and lung. • Gross picture: Gumma may be solitary or multiple, variable in size and rubbery in consistency. The cut surface is greyish yellow with greyish white fibrosis in the periphery. • Fate: • (a) Gumma in solid organs as the liver is gradually replaced by fibrous tissue which contracts and distorts the shape of the organ. • (b) Gumma near the surface as in the subcutaneous tissue or tongue ulcerates. The gummatous ulcer is serpiginous in shape. The edge is deep and punched out (sharp). The floor is greyish yellow and caseous. The base is firm Tertiary syphilis Gumma of nose & palate Ulcerative gumma of hand Gumma of skull III. Tertiary Stage (2) Diffuse syphilitic inflammation: This type of lesion is more common than gumma. It is a diffuse syphilitic reaction with minimal areas of caseation (microscopic gummata) which develop very slowly. Replacement fibrosis occurs in the usual way. The affected organ is firm and its cut surface is greyish white. The lesion occurs in the larynx, aorta, testis, bone and meninges. Tertiary Syphilis of Cardiovascular System I. Syphilis of The Heart:(1) Gumma in the septum (2) Diffuse syphilitic myocarditis and pericarditis. II- Syphilitic Arteritis: (End arteritis obliterans) III- Syphilitic Aortitis: affects the ascending syphilitic aortitis (Coronary ostea stenosis) thoracic aorta because of its rich lymphatics (1)Aortic Incompetence (2)Aortic Aneurysm (3)Stenosis of Coronary Orifices syphilitic aneurysm Congenital Syphilis • • • • • • • The untreated syphilitic mother is very liable to transmit the disease to her foetus after the fourth month of pregnancy, when the Langhan’s layer of the placenta disappears. Abortion may result, or else a severely affected infant may die soon after birth. More frequently the child survives and he may develop syphilitic lesions early or late in life. Pathological Lesions: Placenta: Pale, enlarged, heavy and firm. Spirochaetes are present in large numbers. Early Manifestations of Congenital Syphilis: Appear soon after birth or within two years. They are similar to secondary syphilitic lesions Late Manifestations of Congenital Syphilis: The patient develops syphilitic lesions within 2-30 years congenital syphilis Hutchinson teeth Hepar lobatum perforated palate Leprosy LEPROSY (HANSEN’S DISEASE) • Leprosy is an ancient disease characterized by a long incubation period and a unique predilection for skin and nerves in the cooler parts of the body. • It is a slowly progressive mycobacterial infection caused by Mycobacterium leprae which is an obligate intracellular acid fast bacteria. Mode of infection: • Human-to-human transmission is the usual cause of transimission, but requiring “prolonged and intimate contact.” • The organisms enter through or mucous membranes of nose and respiratory tract. • The incubation period is 5-10 years LEPROSY (HANSEN’S DISEASE) • Types • There is wide spectrum of the disease depend on the competent of host immune response to the organisms. 1- Tuberculoid leprosy (TL): Patients with (TL) have partial T-lymphocyte immunity. 2- Lepromatous leprosy (LL). Patients with LL have little or no T-lymphocyte immunity to M. leprae. 3- Brderline: between the two polar types of the disease with variable degrees of host immunity & resistence LEPROSY (HANSEN’S DISEASE) • Tuberculoid leprosy (TL): • The classic early skin lesion is an anesthetic asymetrical plaque with erythematous borders. • Nerve involvement is dominant. The nerves are enclosed in granulomatous reaction with damage of nerves (mainly sensory nerves with trophic changes) LEPROSY (HANSEN’S DISEASE) Lepromatous leprosy (LL). • Symmetric skin nodules, plaques, and dermal thickening. • “leonine facies” (coarsening of the facial features due to massive infiltration of • the dermis by M. leprae). • Nasal lesions: nodules causing ulceration & nasal obstruction. • Peripheral nerve involvement The nerves become enlarged, and the anesthesia • results in severe ulcerations and loss of tissue ( Trophic lesions). • Hypergammaglobulinemia and secondary amyloidosis. Lepromatous leprosy (LL). leonine facies Lepromatous leprosy (LL). Skin nodules LEPROSY (HANSEN’S DISEASE) Peripheral nerve involvement dominates the clinical features of both types of leprosy. The nerves become enlarged, and the anesthesia results in severe ulcerations and loss of tissue • (Trophic Lesions). CANDIDIASIS (MONILIASIS) • Definition: • Infection by the fungus monilia albicans. • Mode of Infection: The fungus is found in the mouth, intestine and vagina of healthy persons. • Candidiasis is seen in newborns, debilitated patients, children receiving oral corticosteroids for asthma, and after a course of broad-spectrum antibiotics that destroy competing normal bacterial flora. • The other major risk group includes HIV-positive patients CANDIDIASIS (MONILIASIS) • Pathology: • Mucous membranes: The mucosa is hyperaemic and shows small white patches which could be rubbed off. • The patches consists of the fungus filaments and necrotic surface epithelial cells. • The lesion in the oral cavity is called thrush. • Skin: Cutaneous candidiasis can present in many different forms, including infection of the nail proper (onychomycosis), nail folds (paronychia), hair follicles (folliculitis), moist, intertriginous skin such as armpits or webs of the fingers and toes (intertrigo), and penile skin (balanitis). • Candida Vaginitis is an extremely common form of vaginal infection in women, especially those who are diabetic or pregnant or on oral contraceptive pills. • It is usually associated with intense itching and a thick, curd-like discharge. • "Diaper rash" is a cutaneous candidial infection seen in the perineum of infants, in the region of contact of wet diapers. CANDIDIASIS (MONILIASIS) • Pathology: • Visceral Candidiasis: is common in AIDS patients and in those with hematolymphoid malignancies • Lung lesions in the form of tiny yellow nodules. The lesion is a necrotic focus with inflammatory cellular infiltrate around. • Candida Esophagitis. These patients present with dysphagia (painful swallowing) and retrosternal pain; endoscopy demonstrates white plaques and pseudomembranes resembling oral thrush on the esophageal mucosa. • Invasive (disseminated) Candidiasis, implies bloodbome dissemination of organisms to various tissues or organs. • Common patterns include (1) renal abscesses, (2) myocardial abscesses and endocarditis, (3) brain involvement (most commonly meningitis, but parenchymal microabscesses occur), (4) endophthalmitis , (5) hepatic abscesses, and (6) Candida pneumonia Hydatid Disease The disease is caused by development of the larval stage of Echinococcus granulosus in man Pathologial Features: In any organ ( e.g liver or lung) the embryo becomes distended by clear fluid forming Hydatid cyst: • The wall of the cyst is formed is formed of inner germinal layer and outer cuticular layer • From the germinal layer, new cysts may originate • The cysts are surrounded by macrophages, eosinophils, giant cells and fibrosis Hydatid cyst of brain