Pathology of infectious diseases LEC. 2

1. Pathology of infectious diseases LEC. 2 د.ايمان سعود خليفة

2. Learning objectives You should: -recognize acute from chronic infection -Understand and able to explainaetiology,Pathogenesis, pathological features , Clinical features and complication of T.B.

3. Classification of Infectious Disease: • By duration:acute and chronic(most important classification). • By location: local and systemic. • By timing: primary and secondary.

4. Staphylococcal infection: • Staphylococcus aureus are gram-positive cocci that cause acute diseases due to direct infection or due to the production of toxins. It is pyogenic infection. • Pyogenic infection = suppurative infections = pus forming

6. Types of staph infections: Staph infections can be broadly classified into two groups: 1) Skin and soft tissue infections Most infections caused by staph bacteria are relatively minor and only affect the skin or underlying tissue. Common examples include: Furuncle and Carbuncles

7. Furuncle and Carbuncles Furuncle (boil): start at the hair follicles small localized, painful abscess which may rupture extrude pus to the outside and later on will heal. Carbuncle: it is a more extensive lesion &it is dangerous if it occur on the upper half of the face. • Impetigo – a highly contagious skin infection that mainly affects children . caused by staph. or streptococcal infection..

8. askin abscess – a collection of pus that appears as a painful lump under the surface of the skin . • Staphylococcal scalded skin syndrome (SSSS) – a more serious condition that mainly affects infants and young children, where staph bacteria release a toxin that damages the skin, leading to extensive blistering.

9. Furuncle( boil) carbuncle

10. FURUNCLE

11. Impetigo

12. Staphylococcal scalded skin syndrome

13. 2) Invasive infections In a small number of people, a staph skin infection can lead to a more serious, invasive infection deeper within the body. Examples include: Staphylococcal food poisoning is caused by preformed S. aureus toxin present in contaminated food. 1) septic arthritis 2) osteomyelitis 3) pneumonia 4) endocarditis 5) sepsis

14. 6) toxic shock syndrome – life threatening condition  where bacteria release toxins into the blood, which can cause a sudden fever, vomiting, diarrhea, fainting, dizziness, confusion and a rash

15. Streptococcal infections: Streptococci are gram-positive cocci that cause acutesuppurative infections of the skin, oropharynx, lungs, and heart valves. It classify into : Βeta -hemolyticare typed according to their surface carbohydrate antigens : (Group A)It is one of the most frequent bacterial pathogens of humans, The diseases caused by S. pyogenes are in two categories:1. Suppurative diseases, including pneumonia, occur at sites where the bacteria invade and cause tissue necrosis and an acute inflammatory response.

16. 2. Non suppurativediseases occur at sites remote from the site of bacterial invasion. Two major non suppurative post-infectious syndromes are rheumatic fever and acute poststreptococcal glomerulonephritis . (Group B) colonizes the female genital tract and causes sepsis and meningitis in neonates.

17. : Group A βeta –hemolytic Streptococcal infection Responsible for post-infectious syndromes: • rheumatic fever • Post streptococcal glomerulonephritis

18. Types of streptococcal infection: Cellulites: It is caused by invasion of the m.o. to the skin and subcutaneous tissue which will produce a diffuse suppurative inflammation. The infection spread through the lymphatic  L.N  swelling and tenderness of these L.N.

19. cellulitis

20. Clinically: The affected area will be red, edematous, indurated with NO well defined margin. Erysipelas: inflammation is superficial in the skin, spreading in nature with NO suppuration unless deeply infected.

21. erysipelas

22. Scarlet fever: associated with pharyngitis caused by S. pyogenes. most clinical features are caused by its erythrogenic toxin. IT is most common between the ages of 3 and 15 years. It is manifested by erythematous rash that is most prominent over the trunk and inner aspects of the arms and legs. The face is also involved, but usually a small area about the mouth remains relatively unaffected to produce circumoral pallor.

23. Scarlet fever

24. Cholera • Cholera is acute severe diarrheal illness caused by the enterotoxin of Vibrio cholerae,, curved gram-negative rod. • The organism proliferates in the lumen of the small intestine and causes profuse,watery diarrhea, rapid dehydration, and (if fluids are not restored) shock and death within 24 hours of the onset of symptoms.

25. Cholera is epidemic enteritis, usually acquired from contaminated water. • V. choleraeorganisms themselves do not invade the mucosa of the small intestine, but instead cause diarrhea by the elaboration of the potent cholera toxin.

27. This toxin contains a subunit that catalyzes the chemical modification of a G protein within the enterocyte, causing the continuous activation of adenyl cyclase. • The resulting excessive increase in intracellular cAMP results in the massive secretion of electrolytes and water into the intestinal lumen.Fluid and electrolyte loss can advance to shock and death within hours if fluid volume is not replaced.

28. Replacement of lost salts and water can be accomplished by oral rehydration with preparations of salt, glucose, and water. • Cholera subsides in 3 to 6 days, and infection confers long-term immunity.

29. Tuberculosis: Tuberculosis is a chronic, highly communicable disease in which the lungs are the prime target, although any organ may be infected. Etiology: 1)Mycobacterium tuberculosis hominis whichis acquired by Inhalation of aerosols from expectoration of infected individuals and give rise to pulmonary disease. 2) Mycobacterium tuberculosis bovis which is acquired by the ingestion of infected milk and give rise to Oropharyngeal and intestinal tuberculosis.

30. Routes of infection: • inhalation : which cause pulmonary disease. • ingestion : of contaminated milk (milk from infected animal by mycobacterium bovis) intestinal or oropharyngeal T.B. • inoculation: is rare and may cause skin T.B especially between the medical staff.

31. Risk groups: 1) Poor individuals. 2) Chronically ill patients. 3) Old age with low immunity. 4) Chronic diseases: diabetes mellitus, chronic renal failure, chronic lung disease. 5) Malnutrition, alcoholism. 6) Patient with HIV infection.

32. Pathogenesis: Patterns of tuberculosis include the following: 1- Primary tuberculosis : 2- Progressive primary tuberculosis: 3- Secondary (cavitary) tuberculosis:

33. 1- Primary tuberculosis: • Occurs on first exposure to the organism usually in children.  • The source of the organisms is exogenous . • The commonest site is the lung.  • In more than 90% of normal adults, tuberculous infection is self-limited.Mycobacteria are deposited in lung alveoli and are phagocytosed by alveolar macrophages. • The bacilli resist killing by blocking the fusion of the phagosome with the lysosome; they then multiply within the lysosomes of the macrophages.

34. If the patient have natural resistance associated macrophage protein 1 (NRAMP1) which is important in microbial killing leading to unchecked bacteremia without development of effective immune response. • While if patient have defect in this protein then Some macrophages pass to the regional L.N (lymph node) and represent bacillary antigen (related to HLA class II) to the CD4+ T- lymphocyte.

35. The CD4+ cells will secrete γ interferon which is important in the activation of the macrophage, such activated macrophage release many mediators including:- • Tumor necrosis factor TNF that differentiate the macrophages into EPITHELOID cells. • Nitric oxide & free radicals that have bactericidal activity.

36. Some of the epitheloid cells unite and form the LANGHANS GIANT cells. • The accumulation of such epitheloid cells with the giant cells surrounded bya cuff of Lymphocytes forms the so called T.B granuloma which with time may undergo caseous necrosis in its center. • Immunity develops 3 weeks after exposure to .T.B bacilli.

37. The lung lesion of primary tuberculous infection is known as the Ghon focus—a small area of inflammatory consolidation. • The typical lesion is called GHON complex which represents. the involvement of the lung (subpleural area) by T.B granuloma (Ghon focus)+involvement of the HILAR lymph nodes.

38.  the Ghon complex undergoes progressive fibrosis, and  calcification often follows (detectable as a Ranke complex on  radiograph).

39. The importance of primary tuberculosis is: • Induction of hypersensitivity &increase resistance. • The foci of scarring may harbour viable foci for years. • The disease may develop without interruption in immunocompromised persons ( or when the bacteria are highly virulent) which is calledprogressive primary tuberculosis .

40. 2- Progressive primary tuberculosis: In immunologically incompetent hosts, granulomas are poorly formed and Infection progresses to regional lymph nodes or disseminates to multiple sites.

41. 3- Secondary (cavitary) tuberculosis: • Called post primary or adult type or re-infection. • Occur with individuals with previous exposure to T.B bacilli (previously sensitized). • The infection is either exogenous (new infection) or endogenous (reactivation of the primary T.B). • The lesion is usually in the lung Located at the upper lobes near the apex and it is a cavitating lesions. • There is no significant L.N involvement.

45. Morphology: • Both primary and secondary T.B lesions shows the characteristic caseatinggranuloma which is formed by epithelioid macrophages and Langhans giant cells along with lymphocytes, plasma cells, fibroblasts with collagen, and characteristic caseous necrosis in the center. • miliary T.B is called so because the lesions are small tiny yellow white spots similar to millet seeds fed to birds.