1. Chapter 26
Infectious Diseases

2. a LANGE medical book
Pathophysiology of Disease An Introduction to Clinical Medicine Seventh Edition

3. CHAPTER 4
Infectious Diseases

4. Infection and the Body’s Defense Mechanisms
There are several microorganisms that live on and in the human body that do not produce signs of illness
Referred to as indigenous flora, these bacteria can also be helpful
Pathogens are microorganisms that produce signs of illness

5. Infection and the Body’s Defense Mechanisms
The innate immune system
Structural barriers
Skin and mucous membranes
Inflammatory response
The acquired immune system
Humoral system
Cellular immune system
Immunization

6. Most Frequent and Serious Problems
Bacterial Infections
Secondary infections, sexually transmitted infections
Viral Infections
Upper respiratory illnesses
Gastroenteritis
Cold sores
HIV

7. Most Frequent and Serious Problems
Rickettsial Infections
Rocky Mountain Spotted Fever
Fungal Infections
Candida

8. Most Frequent and Serious Problems
Protozoal Infections
Malaria
Helminth Infections
Roundworms

9. TABLE 4–1 Obtaining a history in the diagnosis of infectious diseases.

10. FIGURE 4–1 The fundamental relationships involved in the host-agent-environment interaction model. In the host, pathogenetic mechanisms extend from the level of populations (eg, person-to-person transmission) to the level of cellular and molecular processes (eg, genetic susceptibility).

11. FIGURE 4–2 Phases of the host response to infection
FIGURE 4–2 Phases of the host response to infection. During the earliest stage of initial infection, nonspecific mediators (complement, phagocytes) predominate. Adaptive immunity (production of antibody, stimulation of lymphocytes) requires clonal expansion after recognition of specific antigens. Once immunity toward a specific agent is induced, the immune response remains primed so that the response to reinfection is much more rapid.

12. Symptoms, Signs, and Tests
Rapid onset of muscle aches, fatigue, fever, malaise
Physical exam
Many lesions are characteristic enough to be diagnostic

13. Symptoms, Signs, and Tests
Laboratory testing
Culture: most commonly used for bacteria
Once the bacteria is identified, it is tested for susceptibility to various antibiotics
Gram stains
Allow for an “educated guess” about antibiotic coverage while waiting for the organism to be identified

14. Specific Diseases Staphylococcal Infections
S. aureus can develop into Methicillin Resistant S. aureus and cause serious illness in some patients

15. Specific Diseases Group A Streptococcal Infections
Strep A is the most virulent, and common in upper respiratory infections
Scarlet fever
Necrotizing fascitis

16. Specific Diseases Streptococcus pneumoniae Common cause of pneumonia
Neisseria meningitidis
Meningococcal Menigitis

17. Specific Diseases Haemophilus influenzae
Common cause of ear infections and sinusitis
Other serious illnesses caused by this bacteria have been eliminated through immunization

18. Specific Diseases Legionellosis
Gram negative bacteria that thrives in water reservoirs and cooling towers
A common cause of community acquired pneumonia

19. Specific Diseases Nonfastidious Gram-Negative Rods Enteric bacteria
When these bacteria cause sepsis, they often lead to septic shock with a mortality rate of up to 50%

20. Specific Diseases Anaerobic Bacteria
Bacteria that grow with little oxygen
Sexually Transmitted Infections

21. Specific Diseases Anaerobic Bacteria
Bacteria that grow with little oxygen
Sexually Transmitted Infections

23. Specific Diseases Bacterial Infections Mediated by Exotoxins
Clostridium Family
Tetani (tetanus)
Botulinum (botulism)
Difficile (entercolitis, not exotoxin mediated)
Perfringens (gas gangrene)
Diptheria

24. Specific Diseases Bordetella pertussis (whooping cough)
Not as prevalent in young children due to immunization, though resurgence in older children and adults suggests the vaccine needs to be re-administered

25. Specific Diseases Mycoplasma Disease
Common cause of atypical pneumonia
Lyme Disease
Tick borne disease

26. Specific Diseases
Plague
Tularemia
Brucellosis
Leprosy

27. Specific Diseases Viral Infections
Do not respond to antibiotic therapy and are best treated with supportive mechanisms
Few anti-viral medications are available to decrease the duration of illness
Immunization has decreased the number of viral infections

28. Specific Diseases Measles, Mumps, Rubella, and Varicella
Young children are immunized against these with one vaccine (MMRV)
Smallpox
No longer found in the U.S. due to successful vaccination

29. Specific Diseases Influenza A
Causes wide-spread respiratory disease yearly
Mononucleosis
Epstein-Barr Virus

30. Specific Diseases Herpes Simplex
Type I—mostly oral lesions “cold sores”
Type II—genital lesions
Human Papillomavirus
Some strains associated with the development of cervical cancer

31. Specific Diseases Cytomegalovirus Human Immunodeficiency Virus
Causes AIDS
Rickettsial Infections

33. Specific Diseases Protozoal Disease Malaria Toxoplasmosis
Cryptosporidiosis
Helminthic Infections
Various “worms”
Trichinosis

34. FIGURE 4–3 Commensal bacteria secrete toll-like receptor (TLR) ligands, which bind to TLR on the surface of normal intestinal tissue. This interaction stimulates basal signaling, which protects against cellular injury. Disruption of TLR signaling or antibiotic associated eradication of commensal bacteria result in compromised ability of the intestinal epithelium to withstand injury and repair cell damage. (Redrawn, with permission, from Madara J. Building an intestine—Architectural contributions of commensal bacteria. N Engl J Med. 2004;351:1686.)

35. FIGURE 4–4 Complement reaction sequence and infections associated with deficiency states. (Redrawn, with permission, from Nairn R. Immunology. In: Brooks GF et al, eds. Jawetz, Melnick, and Adelberg’s Medical Microbiology, 23rd ed. McGraw-Hill, 2004.)

36. FIGURE 4–5 Pathogenesis of bacterial valve colonization
FIGURE 4–5 Pathogenesis of bacterial valve colonization. Viridans group streptococci adhere to fibrin-platelet clots that form at the site of damaged cardiac endothelium (A). The fibrin-adherent streptococci activate monocytes to produce tissue factor activity (TFA) and cytokines (B). These mediators activate the coagulation pathway, resulting in further recruitment of platelets and growth of the vegetation (C). (Redrawn, with permission, from Moreillon P et al. Pathogenesis of streptococcal and staphylococcal endocarditis. Infect Dis Clin North Am. 2002;16:297.)

37. FIGURE 4–6 Osler node causing pain within pulp of the big toe in a woman hospitalized with acute bacterial endocarditis. (Osler nodes are painful: remember “O” for Ouch and Osler.) Note the multiple painless flat Janeway lesions over the sole of the foot. (Used, with permission, from David A. Kasper, DO, MBA. Originally published in: Chumley H. Bacterial endocarditis. In: Usatine RP et al, eds. The Color Atlas of Family Medicine. McGraw-Hill, 2009:205–9.)

38. FIGURE 4–7 Pathogenic steps leading to pneumococcal meningitis
FIGURE 4–7 Pathogenic steps leading to pneumococcal meningitis. The pneumococcus adheres to and colonizes the nasopharynx. IgA1 protease protects the pneumococcus from host antibody (A). Once in the bloodstream, the bacterial capsule helps the pneumococcus to evade opsonization (B). The pneumococcus accesses the cerebrospinal fluid through receptors on the endothelial surface of the blood-brain barrier (C). (Redrawn, with permission, from Koedel U et al. Pathogenesis and pathophysiology of pneumococcal meningitis. Lancet Infect Dis. 2002;2:731.)

39. FIGURE 4–8 Pathophysiological alterations leading to neuronal injury during bacterial meningitis. BBB, blood-brain barrier; CBV, cerebral blood volume. (Redrawn, with permission, from Koedel U et al. Pathogenesis and pathophysiology of pneumococcal meningitis. Lancet Infect Dis. 2002;2:731.)

40. FIGURE 4–9 Pulmonary defense mechanisms
FIGURE 4–9 Pulmonary defense mechanisms. Abrupt changes in direction of airflow in the nasal passages can trap potential pathogens. The epiglottis and cough reflex prevent introduction of particulate matter in the lower airway. The ciliated respiratory epithelium propels the overlying mucous layer (right) upward toward the mouth. In the alveoli, cell-mediated immunity, humoral factors, and the inflammatory response defend against lower respiratory tract infections. (C, complement.) (Redrawn, with permission, from Storch GA. Respiratory system. In: Schaechter M et al, eds. Mechanisms of Microbial Disease, 4th ed. Lippincott Williams & Wilkins, 2007.)

41. FIGURE 4–10 Pathogenesis of Vibrio cholerae and enterotoxigenic E coli (ETEC) in diarrheal disease. V cholerae and ETEC share similar pathogenetic mechanisms in causing diarrheal illness. The bacteria gain entry to the small intestinal lumen through ingestion of contaminated food (left). They elaborate an enterotoxin that is composed of one A subunit and five B subunits. The B subunits bind to the intestinal cell membrane and facilitate entry of part of the A subunit (right). Subsequently, this results in a prolonged activation of adenylyl cyclase and the formation of cyclic adenosine monophosphate (cAMP), which stimulates water and electrolyte secretion by intestinal endothelial cells. (Redrawn, with permission, from Vaughan M. Cholera and cell regulation. Hosp Pract. 1982;17(6):145–52.)

42. FIGURE 4–11 Pathogenic sequence of the events in septic shock
FIGURE 4–11 Pathogenic sequence of the events in septic shock. Activation of macrophages by endotoxin and other proteins leads to release of inflammatory mediators and immune modulation resulting in host tissue damage and, in some cases, death. (Redrawn, with permission, from Horn DL et al. What are the microbial components implicated in the pathogenesis of sepsis? Clin Infect Dis. 2000;31:852.)

43. TABLE 4–2 Infections associated with common defects in humoral and cellular immune response.

44. TABLE 4–3 The establishment and outcome of infectious diseases.

45. TABLE 4–4 Diagnosis of infective endocarditis.

46. TABLE 4–5 Proportion of cases of bacterial meningitis in the United States by host age, 2003–2007.

47. TABLE 4–6 Pathogenetic sequence of bacterial neurotropism.

48. TABLE 4–7 Common etiologic agents of community-acquired pneumonia as determined by severity of illness.

49. TABLE 4–8 Common risk factors and causes of pneumonia in specific adult hosts.

50. TABLE 4–9 Approach to GI tract infections.

51. TABLE 4–10 Escherichia coli in diarrheal disease.

52. TABLE 4–11 Clinical definition of sepsis.