Infectious Diseases - Bacteria

PATHOLOGY

Dr. Arlene Santos

_{August 11, 2011}

Infectious Diseases ii:

BACTERIAL INFECTIONS

Pathology 1 | 9

1. Staphylococcal infections

2. Streptococcal & Enterococcal infections 3. Diphtheria

4. Listeriosis

5. Anthrax (discussed in Bioterrorism) 6. Nocardia

 Gram-positive cocci in clusters (grapelike)  Produce disease by:

1. Multiplication & spread in the tissues 2. Production of toxins & enzymes

Note:

Cause myriad of skin lesions: boils, carbuncles, furuncles, SSS (Scalded Skin Syndrome), TSS (Toxic Shock Syndrome), abscess formation, endocarditis, food poisoning, osteomyelitis

1. Catalase

- Positive (+) – Bubble formation when H2O2 is added

2. Coagulase

- Synonymous with invasive pathogenic potential

3. Hyaluronidase

- Hydrolyses hyaluronic acid in the connective tissue  Facilitates spread of infection

4. Staphylokinase

- Results in fibrinolysis

5. Proteinases 6. Lipases

- Degrades lipids on skin surface

- Enables it to produce boils or carbuncles

7. Exotoxins

- α-toxin

 A hemolysin  Damages platelets

 Lethal & dermonecrotic factor  Acts on vascular smooth muscle - β-toxin

 Sphingomyelinase

 Toxic for many kinds of cells including RBCs - δ-toxin

 Detergent-like peptide - γ-Toxin

 A hemolysin (Lyses RBC and phagocytic cells)

8. Leukocidin

- Lyses phagocytic cells

9. Exfoliative toxin

- Causes Scalded Skin syndrome (SSS) /Ritter disease - α & β toxins split the skin by cleaving the protein

desmoglein 1

 Keeps keratinocytes and epithelial cells intact  Part of desmosomes that hold epidermal cells - This leads to loss in barrier function  Infection - SSS affects granulosa layer which can be distinguished

from Toxic Epidermolysis Necrosis (TEN)

10. Toxic Shock Syndrome Toxin (TSS)

- The prototype of a superantigen

- Associated with fever, shock (hypotension) & multisystem involvement

11. Enterotoxin

- Another superantigen

- Causes food poisoning (Acute self-limited diarrhea) - Stimulates vomiting center in the CNS  ENS 

Emesis

Fig. Consequences of Staphylococcal Infection

1. Furuncle/boil

- Focal suppurative inflammation of skin & subcutaneous tissue

- Frequently seen in moist/hairy areas (Face, axillae, groin, legs and submammary folds)

- Starts in a single hair follicle  Develops into a growing & deepening abscess

2. Carbuncle

- Involves a deeper suppuration, spreading laterally beneath the deep subcutaneous fascia (Upper back and posterior neck)  Burrows superficially to erupt in multiple adjacent skin sinuses

3. Hidradenitis: Chronic suppurative infection of apocrine

glands most often in axilla

4. Paronychia: Nail bed infection

5. Felons: Infection on palmar side of fingertips 6. Lung abscess

- S. aureus lung infections

- Extensive neutrophilic infiltrate within the alveoli - Destruction of the alveoli

Note:

Staphylococcus infection in general:

 Histologically, there is separation and production of

purulent exudate

 Marked tissue destruction

Furuncle/boil Carbuncle

Pathologic Findings

Toxins and Enzymes of Staphylococci

Staphylococcal Infections

Pathology 2 | 9

 Gram-positive cocci in pairs or chains

Virulent factors & toxins:

1. Capsule – Resist phagocytosis 2. M protein – Antiphagocytic

3. Complement C5a peptidase – Degrades C5a (chemotactic peptide)

4. Pyrogenic toxin – Cause fever & rash in scarlet fever 5. Pneumolysin - Causes tissue damage and reduces

complement available for opsonization of bacteria

6. HMW glucans – Promote aggregation of bacteria & plaque formation (Streptococcus mutans – Dental carries)

Notes:

 Cause myriad of suppurative infection: Skin, oropharynx,

lungs, heartvalves

 Cause: Post-Strep GN (Glomerulonephritis), Rheumatoid

Heart Fever and Erythema nodosa

 Can be flesh eating bacteria  Causing rapidly progressive necrolytizing fascisitis

Table 1. Common & Important Diseases caused by Streptococci

Infectious Agent Disease/s

Streptococcus pyogenes

(Group A strep)

Pharyngitis, Impetigo, Rheumatic fever, Glomerulonephritis, erysipelas,

Scarlet fever, TSS

Streptococcus agalactiae

(Group B strep) Neonatal sepsis & Meningitis

Enterococcus faecalis &

other enterococci

Abdominal abscess, Urinary tract infection, Endocarditis

Viridans streptococci

(multiple species)

S. mutans - Dental caries;

Endocarditis, Abscesses

Streptococcus pneumoniae

(α-hemolytic strep) Pneumonia, Meningitis, Endocarditis

1. Streptoccocal erysipelas

- Cutaneous erythematous swelling - Boarders are hardly demarcated

- Exotoxin released from group A & C Streptococci - Rapidly spreading erythematous cutaneous swelling with

well-demarcated, serpigenous borders - Pathologic Findings in Streptococcal Infection - Butterfly distribution

2. Streptococcal pharyngitis

- Epiglottic swelling and punctuate abscesses of the tonsillar crypts

- Minimal tissue destruction

- Major antecedent of post-strep GN

Fig. Pharynx showing streptococcal infection

3. Streptococcus mutans

- Metabolize sucrose to lactic acid  Enamel demineralization

- Secret glucans that promote aggregation of bacteria and plaque formation

4. Streptococcus pyogenes

- Scarlet fever assoc with pharyngitis

Histopathology of Streptococcal Infections

- Neutrophilic infiltration of tissues with edema

- Minimal tissue destruction (In contrast to Staph infections) - Abscess formation minimal

 Corynebacterium diptheriae  Gram (+) rod

 Colonizes the oropharynx

 Transmission: Aerosols or skin shedding

 Exotoxin (Phage encoded A-B) blocking of protein synthesis via inhibition of EF-2 function essential for mRNA translation to protein

 Exotoxin causes necrosis of epithelium  Fibrino-suppurative membrane  Formation of pseudomembranes causes inflammation of bronchus

 Tough pharyngeal membrane & toxin-mediated damage in the heart

 Bacterial invasion remain localized but may cause several symptoms as a result of entry of soluble exotoxin into the blood.

Note:

Inclusion of diphtheria toxoid in the childhood vaccine (DPT) does not prevent the colonization of C. diphtheriae but protects immunized children from the lethal effect of the toxin

Corynebacterium diptheriae

↓

Releases an exotoxin ↓

Causes necrosis of epithelium

Outpouring of a dense fibrinosuppurative exudate ↓

Coagulation of exudate on ulcerated necrotic surface ↓

A tough, dirty gray to black superficial membrane  Membrane of diptheria lying within a transverse bronchus  Pseudomembranous inflammation of the bronchus

 Fibrinosuppurative exudates with aggregates of neutrophils mixed with edema fluid and fibrin

 Diptheritic Myocarditis

o Interstitial Mononuclear Inflammation o Necrosis of myocardial fibers with mononuclear

inflammatory cells in between

Pseudomembranous inflammation of the bronchus Diptheritic Myocarditis

Pathologic Findings

Pathogenesis

Diptheria

Pathologic Findings

Pathology 3 | 9

 Listeria monocytogenes – Gram (+) bacillus

Table 2. Infection or Diseases Caused by L. monocytogenes

Population at Risk Infection/Disease

People who consume dairy

products, chicken or hotdogs Food-borne infection Pregnant women Amnionitis

Neonates Granulomatosis infantiseptica Neonates;

Immunosuppressed individuals

Disseminated listeriosis; Meningitis

 Histologic finding: Exudative inflammation (Neutrophilic infiltration of tissues)

 Meningitis

o Gross finding: Purulent exudate within the leptomeninges o Histological finding: Neutrophils within subarachnoid

space & around leptomeningeal vessels o CSF: Gram (+), intracellular bacilli

 In neonates & immunosuppressed individuals: Abscesses alternate with grayish or yellow nodules

 Neonates with L. monocytogenes sepsis: Red papular rash over extremities & abscesses in the placenta

 Nocardiosis  Gram-positive bacilli

 Cause opportunistic infections in immunocompromised patients

Table 3. Diseases caused by Nocardia species

Infectious Agent Disease/s

Nocardia asteroides Respiratory Infections  Brain abscess (May be mistaken to be Tuberculosis because of similar symptoms)

Nocardia brasiliensis Skin infections

 Gram-stain of a sputum: o Smear-beaded o Branched chains o Gram (+) organisms o Found with WBCs

 (+) Acid fast along with TB and M. leprae

Fig. Gram stain showing Nocardia species

 Suppurative inflammation

 Granulation tissue formation & fibrosis in the surrounding area  Granulomas do not form

1. Neisserial infections 2. Whooping cough 3. Pseudomonas infection

4. Plague – not discussed in lecture but included in ppt 5. Chanchroid (soft chancre)

6. Granuloma inguinale  Neisseria species

 Gram (-) diplococci, usually occuring in pairs with or inside WBCs

 Neisseria meningitidis – Attach to epithelial cells of the nasopharynx

 Neisseria gonorrheae – Attach to epithelial cells of mucous membranes of GUT, eye, rectum & throat

 Antigenic variation – Mode to escape the immune response N.meningitidis

1. Capsular polysaccharides - Inhibit phagocytosis 2. Pili

- Enhance attachment to host cells - Adhesion

3. Class 1,2 & 3 proteins

- For pore formation in cell wall 4. Class 5 protein (Opa protein)

- For adhesion to host cells 5. Lipooligosaccharide

- Has endotoxic effects N. gonorrheae

- 2nd leading cause of bacterial STD in States 1. Long Pili

- Enhance attachment to CD46 in epithelial cells - Enhance resistance to phagocytosis

2. Protein I (Por protein) - For pore formation 3. Protein II (Opa protein)

- For adhesion of gonococci w/in colonies - For attachment to host cells

- Associates w/ Por protein in pore formation 6. 4.Lipooligosaccharide

- Has endotoxic effects 7. Other proteins:

- Lip protein: Heat modifiable protein - Iron-binding protein

- IGA 1 protease-inactivates IGA1, a major mucosal Ig

Table 4. Infections & Diseases caused by Nesseria sp.

Infectious Agent Infection/s

Neisseria meningitidis Bacterial meningitis Meningococcemia Neisseria gonorrheae Male – Urethritis

Female – Mostly asymptomatic but infection is present in endocervix  Spread to vagina 

Fallopian tube  Obliteration  Infertility Children – Gonococcal ophthalmia neonatorum; during passage in birth canal 

conjunctivitis

Individuals who lack the complement protein that form the membrane attack complex –

Disseminated gonococcal disease (gonococcal arthritis-dermatitis syndrome) Uncommon: Meningitis & Eye infections in

adults

Determinants of Pathogenicity

Neisserial Infections

GRAM-NEGATIVE BACTERIAL INFECTIONS

Pathologic Findings

Nocardia

Pathologic Findings

Pathology 4 | 9

 Meningococcal Infection

- Overwhelming septicemic infection

- Rapidly progressing decreased BP  Shock

- Spread to subarachnoid space  Meningitis (In children & adults)

 Waterhouse–Friderichsen syndrome – Fulminant form of

meningococcemia associated with bilateral adrenal hemorrhage

 Meningococcal meningitis

- Polymorphonuclear infiltration of meninges - Aggregates of polymorpholeukocytes (Neutrophils)

Maculopapular rashes in N. meningitides infection

Bilateral adrenal hemorrhage: Waterhouse-Friderischen syndrome

Neutrophilic infiltration around the meninges and its vessels

 Caused by Neisseria gonorrhea  Adolescent are at high risk

 Often asymptomatic, may lead to pelvic inflammatory disease, infertility and ectopic pregnancy

 Transmitted by oral, anal or vaginal intercourse  Perinatal transmission

 S/S: Urethral infection, vaginal discharge, “Morning drop”  Dx: Gram stain, culture

 DNA screening

Pathologic Findings

Fig. Urethral discharge in gonorrhoeal infection: “Morning drop”

Acute suppuration ↓ Chronic inflammation Fibrosis  Bordatella pertussis  Gram (-) coccobacilli

 Paroxysmal stage - Cough develops its explosive character & characteristic whoop upon inhalation

1. Pili

2. Virulence factors 3. Filamentous agglutinin 4. Pertussis toxin 8. Adenyl cyclase toxin 9. Dermonecrotic toxin 10. Hemolysin

11. Tracheal cytotoxin 12. Lipopolysaccharide

Pathogenesis of Whooping Cough

B. pertussis

↓

Enters through the respiratory tract ↓

Adhesion & Multiplication on epithelial surface of trachea & bronchi

Interference with ciliary action (Paralysis of cilia) ↓

Release of toxins & substances w/c irritate surface cells ↓

Coughing & Lymphocytosis ↓

Focal necrosis of the epithelium Polymorphonuclear infiltration

Peribronchial inflammation Interstitial pneumonia

↓

Obstruction of smaller bronchioles by mucus plugs (Mucosal

erosion)

↓ Atelectasis

Decreased oxygenation of blood ↓

Convulsions in infants w/ whooping cough

Note:

There is Lymphocytosis not Neutrophilia even though this is a bacterial infection

 Bacilli entangled with cilia of the bronchial epithelial cells:

Fig. Bacilli caught by the cilia of bronchial epithelium

 Pseudomonas aeruginosa  Gram-negative bacillus

 Causes opportunistic infections in the following settings: 1. Disruption of skin & mucosa

2. Use of intravenous or urinary catheters

3. Neutropenia (Example: During cancer chemotherapy)

Note:

Common in hospital acquired infection and is actually the number 1 cause of nosocomial infection

Pseudomonas Infection

Pathologic Findings

Determinants of Pathogenicity of B. pertussis

Whooping Cough

Gonorrhea

Pathology 5 | 9

1. Pili

2. Adherence proteins 3. Lipolysaccharide

4. Alginate  Prevents antibodies, antibiotics and

complements from acting to Pseudomonas due to biofilm

formation

5. Exotoxin A  Inhibits protein synthesis 6. Exoenzyme S

7. G proteins

8. Phospholipase C  Lyse RBC and pulmonary surfactant 9. Elastase  Degrades IgG and ECM proteins

10. Iron-containing compounds  Toxic to endothelial cells  Vascular lesions

11. Mucoid exopolysaccharide called alginate forming a slimy biofilm that protects bacteria from antibodies

1. Infection of wounds & burns (Source of sepsis) 2. Meningitis

3. Necrotizing pneumonia 4. Otitis externa (Swimmer’s ear) 5. Eye infection

6. Ecthyma gangrenosum (Lesions in patient with skin burns) - In skin burns, it proliferates widely, penetrating deeply into

veins and spreads hematogenously - Skin lesions in sepsis

- Necrotic & hemorrhagic oval skin lesions

 Organisms forming a perivascular blue haze in blood vessel walls +Thrombosis + Hemorrhage  Highly suggestive of P.

aeruginosa infection

Fig. Perivascular blue haze in blood vessels

Note:

It is NOT pathognomonic yet highly suggestive of Pseudomonas infection. There is bronchial obstruction in a cystic fibrosis patient due to alginate production.

 Caused by Haemophilus ducreyi  Sexually transmitted

 Gram (-) bacillus

 One of the most common causes of genital ulcers in Africa & Southeast Asia

 Manifests as a painful genital ulcer in contrast with the genital ulcer of granuloma inguinale which is painless

 Called chancroid or soft-chancre in contrast to syphilis which have hard chancre

 Ulcer is not indurated (hardened) and multiple lesions may be present

 If untreated, inflamed and enlarged nodes (buboes) may erode the overlying skin

 Dx: Culture

 In males – Usually on penis  Chancroid in a female

o Starts as an erythematous papule  Ulcer (Has a base covered by shaggy yellow exudate)

o Ulcerate in skin with draining exudate o Lesion is on the mons pubis

Fig. Chancroid Manifestation

 Sexually transmitted disease

 Caused by Klebsiella granulomaris (Formerly called

Calymmatobacterium donovani)

 Coccobacillus

 Mode of transmission: Sexual contact

 Caused by Calymmatobacterium donovani

 Gross: Painless genital ulcers w/ rolled borders & a friable base

 Surrounding granulation tissue soft and sharply demarcated  Single or several

 Soft, sharply demarcated areas of granulation tissue that bleeds easily

Fig. Painless ulcer

 Histologically:

o Dense dermal inflammatory infiltrate (Histiocytes & plasma cells) with small abscesses

o Marked epithelial hyperplasia at the border of ulcer: Pseudoepithelial hyperplasia

 Diagnosis: Donovan bodies – Small, round, encapsulated coccobacilli in macrophages or histiocytes

 Wright stain of a smear of the lesion-Donovan bodies:

Fig. Donovan bodies

 Acid fast bacteria due to mycolic acid in cell wall  Obligate aerobes, non-encapsulated, non-spore forming,

slowly growing

Modes of Transmission

 MTb

o Aerosol spread: Droplet formation (Coughing or sneezing)  M. bovis

o Ingestion (Not common due to pasteurization)  M. avium

o Intracellular complex (MAC) widely disseminated infection o AIDS patients – Abundant acid-fast bacilli within

macrophages

MYCOBACTERIUM

Pathologic Findings

Pathology of Granuloma Inguinale

Granuloma Inguinale (Donovanosis)

Pathologic Findings

Chancroid

Pathologic Findings in Necrotizing Pneumonia

Infections and Diseases caused by P. aeruginosa

Pathology 6 | 9

 Caused by M. tuberculosis  An acid-fast bacillus

Pathogenesis

- Ability to escape killing by macrophages - Type 4 hypersensitivity reaction

 Cord factor

 Lipoarabinomannan (LAM) – Inhibits macrophage activation

 Secretion of TNF  (Fever, tissue damage & weight loss)

 Complement activated on the surface of MTb opsonize and facilitate its uptake by MAC Complement receptor

Fig. The Natural History & Spectrum of Tuberculosis

(fig 8-28 p.369 of Robbins). Study this figure.

 0-3 weeks after onset

 Pathology of Primary Tuberculosis

o Presence of TB granuloma/tubercle in lower lobe o Ghon complex:

 Ghon focus (Gray white inflammation) + lymph node  Ranke complex – Ghon complex becomes fibrotic and

is the radiologically detectable calcification of the Ghon complex

 The focus undergoes caseous necrosis

Histopathology of Tuberculosis

- A granuloma without central caseation - Acid-fast Stain of Mycobacterium tuberculosis - Presence of TB granuloma in lung parenchyma - Presence of epitheloid cells

 If epitheloid cells form a horse-shoe pattern, is called

Langhans Giant Cells

- At the periphery, lymphocytes are seen

Fig. This is an acid fast stain of Mycobacterium tuberculosis (MTB). Note the red

rods--hence the terminology for MTB in histologic sections or smears: Acid fast bacilli

Fig. Macrophages packed with Mycobacteria

 Immunosuppressed individuals without cellular immunity do not form granulomas

 No central caseation

 Instead, foamy macrophages containing mycobacteria are found

Fate of Primary Tuberculosis

- Healed and become calcified: 90%

- Progression of TB: Spread by contiguity or by erosion into bronchi  Disseminate

- Miliary TB – Hematogenous spread of TB throughout the body  Numerous minute yellow-white foci

Fig. Lungs of a patient with secondary TB

 > 3 weeks

 Post-primary tuberculosis

 Reactivation of primary tuberculosis or re-infection in a previously sensitized person

 Granuloma in the apex of lung (due to high O2 content)  2 features: Caseation necrosis & Cavities (cavitation)  Resistant to TB: Heart, striated muscle, thyroid gland &

pancreas

 Yellow/white areas of consolidation in apex  Presence of cavitation

Fate of Secondary Tuberculosis

- Progressive pulmonary tuberculosis – TB erodes bronchi and vessels  Hemoptysis

- Miliary Pulmonary Disease – TB drains into lymphatics to veins and circulate back to the lungs  “Millet seed” appearance

- Endobronchial, Endotracheal & laryngeal TB

- Systemic Miliary TB – Ehen it reaches systemic arterial system

- Isolated Organ TB – May appear in any organ/tissue (Meninges, kidney, adrenals, bones, fallopian tubes& vertebrae)

- Lymphadenitis (Occurring in cervical region: Scrofula) - Intestinal TB

Fig. Miliary Tuberculosis of the Spleen: Minute yellow/white foci of consolidation

and inflammation

Secondary TB

Primary Pulmonary TB

Pathology 7 | 9

Diagnosis of Tuberculosis

- Clinical history, PE and radiologic findings - AFB smears and culture

- Histological findings

- PCR – Assay (Advanced rapid and sensitive) - However “culture” – Gold standard (Testing for drug

susceptibility and multiple drug resistance)

 MAC is uncommon except among people with AIDS and low numbers of CD4+ lymphocytes (<60 cells/mm3)

 Hallmark of M. avium infection – Abundant acid-fast bacilli within macrophages

How does TB manifest in HIV patients?

- Patients with CD4+ T-cell count: >300 cells/mm3: Usual secondary TB

- Patients with <200 cells/mm3: Primary or progressive TB - Other features :

 Increase sputum smear negativity  (-) PPD

 Absence of granulomas

Pathology of MAC Infection

- The lymph nodes in this mesentery, best seen at the left, are enlarged and have cut surfaces that appear yellow-tan - These nodes are filled with sheets of Mycobacterium

avium-complex (MAC) organisms, and the immune response is so poor in this AIDS patient that there is no focal granuloma formation

 M. leprae  Delayed hypersensitivity reaction

 Tuberculoid Leprosy

o Less severe form, dry scaly lesions with lack of sensation o Focal areas of skin pallor & anesthesia due to early

involvement of nerves

o Basic lesion is a granuloma just like MTb o Bacilli are almost never found hence the name

“Paucibacillary” leprosy

o Strong T cell-immunity (Has TH1 response  Production of IL2 and IFN-γ as with MTb)

 Lepromatous Leprosy

o Severe form, also called anergy leprosy because of unresponsiveness (anergy) of the host immune system o Present with nodular lesion

o Disfiguring nodularity of the skin coalesce  Leonine facie o Peripheral nerves affected late

o Skin biopsy will show no granuloma but abundance of lymphocytes

o Lesions with large aggregates of lepra cells (Lipid laden macrophages) or globi (Filled with masses of acid-fast bacilli) hence the name “Multibacillary” leprosy

o Granuloma formation will not happen because of failure

of TH1 response

Pathology of Leprosy

- Inflammatory infiltrates in the endoneural & epineural compartments

- Cells within the endoneurium contain acid-fast positive lepra bacilli

- Presence of hypopigmented maccule - Skin nodules coalesce

Fig. Lepromatous TB. AFB within macrophage: Red-snappers

 Caused by Treponema pallidum

 Usual mode of transmission: Sexual intercourse  Can be transmitted to the fetus during pregnancy  Gross: Painless, shallow ulcer (hard chancre)

 Micro: Ulceration, chronic inflammation (Predominance of plasma cells) & vasculitis

 Treatment: PCN  Diagnosis

o Dark-field examination;

o Immunofluorescence techniques

o VDRL (Venereal Disease Research Laboratory test) o RPR (Rapid Plasma Region)

o Treponema pallidum (Dark field microscopy)

Fig. Protean Manifestations of Syphilis

 Spirochetes are found within the chancre (lesion of primary syphilis)

 Syphilitic chancre in the scrotum  Hard chancre

Fig. LPO - Primary syphilis of the vulva. Note ulceration of epithelium with necrosis,

neutrophil infiltrates. Below epithelium: Mononuclear inflammatory cells, lymphocytes, plasma cells, histocytes

Primary Syphilis

Syphilis

SPIROCHETES

Leprosy (Hansen’s disease)

Pathology 8 | 9

marked scarring and fibrosis of gumma

 Mucocutaneous changes – Maculopapular, scaly or pustular  Condylomata lata – Broad-based elevated plaques

 Lymphadenopathy is common in 2° syphilis infection

 3 characteristics:

1. Cardiovascular syphilis 2. Neurosyphilis

3. Benign syphilis

 Ruptured syphilitic aneurysm – Aortic arch (Syphilitic aortitis)  Gumma – Granuloma or nodular lesions due to delayed

hypersensitivity

 Primary and secondary are highly contagious, tertiary is not and occur approximately 1 out of 3 untreated patients

 Occur during 1° or 2° when spirochetes are most abundant  Saddle nose

 Hutchinson teeth

 Late stages  Triad of Hutchinsons teeth, interstitial keratitis,

eight-nerve deafness H-IK-ED)

 Caused by Borrelia burgdorferi

 Transmitted by tiny Ixodes deer ticks (Babesia & Erlichia)  Major arthropod borne disease in USA, Europe & Japan  Involving multiple organs

 Distinctive feature of Lyme arthritis – Arteritis with onion-skin-like lesions

 Late stage: Extensive erosion of cartilage in large joints

Fig. Clinical Stages of Lyme Disease

 Erythema chronicum migrans (ECM) – Stage 1: o Expanding area of redness with a pale center

NOTE:

 Much of the pathology associated with B. burgdorferi is

thought to be secondary to the immune response against the bacteria and the inflammation that accompanies it.

 Lyme arthritis: Villous hypertrophy, lining cell hyperplasia

and abundant lympho and plasma cell

 Distinctive feature: Onion skin-like lesion resembling in SLE  May have extensive erosion of cartilage

 Clostridium perfringens – Appear as box-shaped, gram (+) bacilli

Table. Diseases caused by Clostridium

Infectious Agent Disease/s

1. C. perfringens, C. septicum Cellulitis Gas gangrene 2. C. tetani Tetanus 3. C. botulinum Botulism

4. C. difficile Pseudomembranous colitis

Note:

C. botulism release neurotoxin which blocks synaptic release of ACh  Paralysis of respiratory and skeletal muscle

Histopathology of Clostridium perfringens

- Gas bubbles are caused by bacterial fermentation - Gangrenous tissue with C. perfringens

- Presence of gram (+) box shapped bacilli

Cellulitis - Foul odor, thin discoloured exudate

Bluish-black friable to semi-fluid tissue which occurs at site of muscle necrosis

 Most common bacterial disease in the world  Leading cause of infertility

 Leading cause of blindness worldwide  Often asymptomatic

 Life cycle: Intracellular – 2 forms: Elementary body (metabolically inactive) & Reticulate body (metabolically active)

 Dx: Amplified DNA and flourescent monoclonal AB screening  C. trachomatis serotype A-C: Trachoma (Blindness),

keratoconjunctivitis

 Serotype D-K: Infection and inclusion conjunctivitis  L1-L3 serotype: Lymphogranuloma venereum (Chronic

ulcerative disease)

Chlamydial Infections

OBLIGATE INTRACELLULAR BACTERIA

Clostridial Infections

ANAEROBIC BACTERIA

Pathology of Lyme Disease

Lyme Disease

Congenital Syphilis

Tertiary Syphilis

Secondary Syphilis

Pathology 9 | 9

 Male: o Urethritis o Epidydimitis

o Mucopurulent discharge (Predominance by PMN) o Dysuria

o Frequency of urination  Females:

o Trachomatis o Urethritis

o Cervicitis lead to sterility and ectopic pregnancy

Fig. Chlamydia urethrittis. Note mucupurulent discharge like gonorrhea

 Caused by Chlamydia serotypes L1, L2 & L3  It is a chronic ulcerative dx

 Often confused w/ syphilis, herpes or chancroid  Mainly affects lymphoid tissue

 Initial ulcer ordinarily pass away unnoticed

 Initial clinical manifestation: Swelling of the inguinal lymph node due to stellate abscesses surrounded by epithelioid cells  Extensive scarring  Fistulas & strictures

 Diagnostic tests: o Frei test o Tissue culture

o Monoclonal antibody test

 Rayney: 11 cases of SCCA on lymphogranulomatous strictures

Pathologic findings in Lymphogranuloma venereum

- Enlarged lymph nodes in both groins - Groove Sign

 Shallow depression, linear fibrotic lesion parallel to inguinal ligamement

 Deen in ingunal area in males and in pararectal region in females

 Most Rickettsial are transmitted by insect vectors o Q fever – Aerosols

o Rickettsia prowazekii – Epidemic typhus: Lice

o Rickettsia rickettsii and others - RMSF – Ticks o Orienta tsutsugamushi – Scrub typhus – Mites

o Mnemonics: Smell feet  SMEL FT

 Tropism: Endothelial cells in blood vessels  Rashes  Predominantly infect endothelial cells & vascular smooth

muscle cells  Vasculitis and disruption  Vascular leakage  Hypovolemic shock

 Rickettisal  Enter skin or with scratching of the skin covered with insect feces  Vholesterol containing receptor  Endocytosed into phagolysosomes  Escapes into cytosol  Vauses cell lysis or infects other cells

 Eschar  Hemorrhagic rash

 Microscopically thrombosed vessels – Vasculitis  Dx: Immunostaining & antibody detection

Note:

They lyse endothelial cell in typhus group or spread from cell to cell in spotted fever group

 Rash

 Eschar – Punched out ulcer covered by a black scar  Peripheral blood granulocyte (Band neutrophil) containing

Ehrlichia inclusion in the cytoplasm

Band neutrophil with Ehrlichia inclusion(morulae) shaped like

mulberries

Typhus nodule in the brain-composed of focal microglial proliferation with an inflammatory

infiltrate of T lymphocytes & macrophages

Rocky Mountain Spotted Fever with a thrombosed vessel & vasculitis: Thrombus formation with vasculitis

Inflammation infiltrate within vascular wall

Note:

RMSF – Hemorrhagic rash that extends over entire body, increase palms and soles is hallmark of RMSF

1. Robbin’s Pathologic Basis of Disease (IMPORTANT!!) 2. Lecture of Dr. Arlene Santos

3. Powerpoint and Recording of the lecture

1. What organism causes Skin Scalded Syndrome 2. The no. 1 cause of nosocomial infection

3. Ghon complex becomes fibrotic and is the radiologically detectable calcification of the Ghon complex

4. Chancroid is the manifestation of this organism

5. Aside from Mycobacterium species, this family is also an acid fast bacilli

6. Chlamydia serotype L1-L3 can cause this disease 7. At what stage of Lyme disease can chronic arthritis be

manifested?

8. Lymphocytosis is manifested in this bacterial infection 9. Fulminant form of meningococcemia

10. What organism can cause Rocky Mountain Spotted Fever?

1. Staphylococcus aureus 2. Pseudomonas aeruginosa 3. Ranke Complex

4. Haemophilus ducreyi 5. Nocardia species

6. Chronic Lymphogranuloma venerum 7. Stage 3

8. Pertussis/Whooping Cough

9. Waterhouse-Friderichsen Syndrome 10. Rickettsia rickettsii

Tip: Study/Correlate/Integrate it with the lectures we had in Microbiology especially this trans so that you’ll be able to finish faster. We didn’t explain the virulence factors/toxins in full detail because it was already in Micro-trans. Be responsible to read it. Hope that this can really help. God Bless!! =)

REMARKS

ANSWERS

REVIEW QUESTIONS

REFERENCES

Pathology

Rickettsial Infections

Lymphogranulma venereum

Pathologic Findings