patoloji-ders-notlari

Title

Serdar Balcı

Transmission and Dissemination of Microbes

Serdar BALCI, MD

How microbes enter body?

Microbes enter the body if they overcome the natural barriers and defense mechanisms

Natural barriers

Intact Skin

Mucosa

Blood Brain Barrier

Natural barriers are physical barriers and produce antimicrobial substances

Defense mechanisms

Saliva

Tear

sIgA

Peyer’s patches

Routes of Entry of Microbes

Breaches in the skin

Inhalation

Ingestion

Sexual transmission

Infections occur in otherwise healthy persons

• Respiratory, gastrointestinal, or genitourinary tract infections
  • Virulent microorgansims
  • Capable of damaging or penetrating intact epithelial barriers
• Skin infections
  • Damaged sites (cuts and burns)
• Genitourinary infections
  • HPV, damaged cervical epithelium

SKIN

Skin

• Dense, keratinized outer layer
• A natural barrier to infection
• Low pH of the skin (<5.5), presence of fatty acids
  • inhibit growth of microorganisms other than the normal flora
• Normal flora
  • including potential opportunists
  • S. aureus and C. albicans

Microorganisms penetrate through breaks in the skin

Superficial pricks → fungal infections

Wounds → staphylococci

Burns → Pseudomonas aeruginosa

Diabetic and pressure-related foot sores → multibacterial infections

From secretions of dead body → Ebola

Intravenous catheters in hospitalized patients → local or systemic infection

Needle sticks → HBV, HCV, HIV

Farklı isimlendirmek gerekirse

Çorum-Yozgat Kanamalı Ateşi

• Insect or animal bite
  • Fleas, ticks, mosquitoes, mites, and lice
• Crimean-Congo hemorrhagic fever
  • Tick bite
• Arboviruses
  • Causes of yellow fever and encephalitis
• Bacteria
  • Plague, Lyme disease, Rocky Mountain spotted fever
• Protozoa
  • Malaria, leishmaniasis
• Helminths
  • Filariasis

Animal bites

Bacteria or certain viruses

Rabies

Microorganisms penetrate through intact skin

• Schistosoma larvae
  • Released from freshwater snails
  • Penetrate swimmers’ skin
  • **Enzymes that dissolve the extracellular matrix. **
• Fungi (dermatophytes) can infect intact stratum corneum, hair, and nails

GASTROINTESTINAL TRACT

Gastrointestinal Tract

Food or drink contaminated with fecal material

Natural disasters (floods, earthquakes), diarrheal diseases

Acidic gastric secretions

• An important defense mechanism
• Lethal for many gastrointestinal pathogens
• Healthy volunteers not infected by V. cholerae unless they are fed 10 11 __ organisms__
• Neutralizing the stomach acid reduces the infectious dose by 10,000-fold
• Shigella and Giardia cysts
  • resistant to gastric acid
  • fewer than 100 organisms of each can cause illness

Other defense mechanisms of GI

Viscous mucus layer covering the intestinal epithelium

Lytic pancreatic enzymes and bile detergents

Mucosal antimicrobial peptides called defensins

Normal flora

Secreted IgA antibodies

Peristalsis

Mucosa-associated lymphoid tissue (MALT)

• **Plasma cells in MALT make IgA antibodies **
• Lymphoid aggregates are covered by a single layer of specialized epithelial cells called M cells
  • transport of antigens to MALT
• Gut pathogens use M cells to enter the host from the intestinal lumen
  • Poliovirus, Enteropathic Escherichia coli, V. cholerae, Salmonella typhi, Shigella flexneri

When does infection occur?

• Local defenses are weakened
  • Low gastric acidity
  • Antibiotics that alter the normal bacterial flora (pseudomembranous colitis)
  • Stalled peristalsis
  • Mechanical obstruction
• Organisms develop strategies to overcome these defenses

Viruses

• Hepatitis A, Rotavirus
  • Lack envelopes
• Enveloped viruses are inactivated by bile and digestive enzymes

Enteropathogenic bacteria

• S. aureus
  • **Grow in food, release powerful enterotoxins → food poisoning **
  • without any bacterial multiplication in the gut
• V. cholerae and enterotoxigenic E. coli
  • Bind to the intestinal epithelium
  • Multiply in the overlying mucous layer
  • Release exotoxins that cause epithelial cells to secrete large volumes of fluid
  • Watery diarrhea
• Shigella, Salmonella, and Campylobacter
  • Invade locally, damage the intestinal mucosa and lamina propria
  • Ulceration, inflammation, and hemorrhage
  • **Dysentery **
• Salmonella typhi
  • passes from the damaged mucosa through Peyer’s patches and mesenteric lymph nodes and into the bloodstream
  • systemic infection

Fungal infections in GI tract

• Occurs mainly in immunologically compromised persons
• Candida
  • part of the normal gastrointestinal flora
  • oral thrush or membranous esophagitis
  • stomach, lower gastrointestinal tract, and other organs

Intestinal protozoa

• Transmitted as cysts
• Resist stomach acid
• Convert to motile trophozoites
• Attach to sugars on the intestinal epithelia through surface lectins
• Giardia lamblia
  • attaches to the epithelial brush border
• Cryptosporidia
  • are taken up by enterocytes
• E. histolytica
  • kills host cells by contact-mediated cytolysis through a channel-forming pore protein
  • ulceration and invasion of the colonic mucosa

Color Atlas Of Pathology

Color Atlas Of Pathology

Intestinal helminths

• Cause disease when in large numbers
• By reaching ectopic sites
• Ascaris lumbricoides
  • by obstructing gut
  • invading and damaging the bile ducts
• Hookworms
  • iron deficiency anemia by sucking blood from intestinal villi
• Diphyllobothrium, the fish tapeworm
  • anemia by depriving the host of vitamin B12
• Trichinella spiralis larvae
  • encyst in muscle
• Echinococcus larvae
  • Grow in the liver or lung

RESPIRATORY TRACT

Microbes are inhaled in dust or aerosol particles

• Large particles
  • Trapped in mucus in the nose and the upper respiratory tract
  • **Transported by ** ciliary action __ to the back of the throat, swallowed__
• Smaller than 5 µm
  • Travel directly to the alveoli
  • Phagocytosed by ** alveolar macrophages **, neutrophils

Viruses

• Attach, enter epithelial cells in the lower respiratory tract and pharynx
• Influenza viruses
  • Hemagglutinin proteins
  • Bind to sialic acid on the surface of epithelial cells
  • Host cell to engulf the virus
  • Replication within the host cell

Impaired Ciliary Acitivity

• Haemophilus influenzae, Mycoplasma pneumoniae, Bordetella pertussis
  • release toxins that impair ciliary activity
• S. pneumoniae and S. aureus
  • Cause pneumonia subsequent to influenza
  • Viral infection causes loss of the protective ciliated epithelium

Damage to ciliary activity

• Chronic damage
  • Smokers
  • Cystic fibrosis
• Acute injury
  • Intubated patients
  • Aspirate gastric acid

M. tuberculosis

Avoid phagocytosis

Avoid destruction after phagocytosis

Escapes killing within the phagolysosomes of macrophages

Opportunistic fungi

• Infect the lungs when cellular immunity is depressed
  • Leukocytes are reduced in number
• P. jiroveci in patients with AIDS
• Aspergillus after chemotherapy

UROGENITAL TRACT

Urinary Tract Infections

UT is invaded from the exterior by way of the urethra

Flushing of the urinary tract with urine serves as a defense against invading microorganisms

Urine in the bladder is normally sterile

N. gonorrhoeae, E. coli adhere to the urinary epithelium

Anatomy is important in UT infection

• Women have more than 10 times as many urinary tract infections as in men
  • Length of the urethra
    • 5 cm in women, 20 cm in men

Urinary tract infections

• Obstruction
  • compromise normal defenses
  • Increase susceptibility to urinary tract infections
• Spread in retrograde fashion
  • From the bladder up to the kidney

Vagina has normal flora

Low pH

Catabolism of glycogen in the normal epithelium by lactobacilli

Normal under estrogen

Antibiotics kill the lactobacilli → Overgrowth of yeast → Vaginal candidiasis

Vertical Transmission

• Placental-fetal transmisions
  • Rubella during first trimester
• Transmission during birth
  • Gonococcal, chlamidial conjunctivitis
• Postnatal transmission
  • Milk
  • CMV, HIV, HBV

SPREAD AND DISSEMINATION OF MICROBES WITHIN THE BODY

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Microorganisms proliferate locally, at the site of initial infection

Penetrate the epithelial barrier and spread to distant sites by way of the lymphatics, the blood, or nerves

• Superficial infections stay confined to the lumen of hollow viscera
  • V. cholerae
• Adhere to, proliferate in or on epithelial cells
  • papillomaviruses, dermatophytes

Secrete lytic enzymes which destroy tissue and allow direct invasion

• S. aureus
  • secretes hyaluronidase
  • degrades the extracellular matrix

Invasive microbes initially follow tissue planes of least resistance and drain to regional lymphatics

• S. aureus
  • Travel from a localized abscess to the draining lymph nodes
  • Lead to bacteremia and spread to deep organs
    • heart, bone

Microorganisms spread in the blood or lymph either free in extracellular fluid or within host cells

• Viruses
  • poliovirus, HBV
• Bacteria and fungi
• Protozoa
  • African trypanosomes
  • All helminths

Blood cells carry microbes

• Leukocytes
  • Herpesviruses
  • HIV
  • Mycobacteria
  • Leishmania
  • Toxoplasma
• RBC
  • Plasmodium
  • Babesia

Virus transmission

• Locally from cell to cell
  • Replication and release of infectious virions
  • HPV
• Fusion of host cells
  • Herpes
• **Transport within nerves **
  • Rabies, varicella-zoster

Infectious foci seeded by blood

• Can be single and large
  • Abscess, Tuberculoma
• Multiple and tiny
  • Miliary tuberculosis
  • Candida microabscesses

Bloodstream

• Sporadic bloodstream invasion by low-virulence or nonvirulent microbes
  • during brushing of teeth
  • common, quickly controlled by normal host defenses
• Disseminated viremia, bacteremia, fungemia, or parasitemia by virulent pathogens
  • fever, low blood pressure, and multiple other systemic signs and symptoms of sepsis
• Massive bloodstream invasion by bacteria can rapidly lead to fatal sepsis, even in previously healthy persons

Manifestations appear distant from the point of microbe entry

• Varicella-zoster and measles
  • Enter through the airways → rashes in the skin
• Poliovirus
  • Enters intestine → Kills motor neurons to cause paralysis
• Schistosoma mansoni
  • Penetrate the skin → Localize in blood vessels of the portal system and mesentery, damage the liver and intestine
• Schistosoma hematobium
  • Localizes to the urinary bladder and causes cystitis
• Rabies
  • Site of a bite → brain by retrograde transport in sensory neurons, encephalitis, death

RELEASE FROM THE BODY AND TRANSMISSION OF MICROBES

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Transmission depends on the hardiness of the microbe.

**Bacterial spores, protozoan cysts, and thick-shelled helminth eggs can survive in a cool and dry environment. **

Less hardy microorganisms must be quickly passed from person to person, often by direct contact.

Desquamated Skin

S. aureus, dermatophyte fungi are shed in the desquamated skin

Saliva

Saliva include mumps virus, cytomegalovirus, and rabies virus

Respiratory secretions

• Talking, coughing, and sneezing
• Influenza viruses
  • Large respiratory droplets
  • Travel no more than short distances
• M. tuberculosis and varicella-zoster virus
  • Small respiratory droplets
  • Dust particles
  • Travel long distances
• M. tuberculosis are infectious only when lesions are open to the airways

Stool

Shigella, Giardia lamblia, rotavirus

Pathogens that replicate in the liver (hepatitis A virus) or gallbladder (Salmonella serotype typhi) enter the intestine in bile and are shed in stool

Hepatitis A, E, Poliovirus, Rotavirus in epidemic outbreaks

Parasite eggs

Blood

• Invertebrate vectors
  • Plasmodium spp
  • Arboviruses
• Blood transfusion
  • Reuse of equipment
  • Sharing of needles, among drug abusers
  • Healthcare personel
  • Blood bank

Urine

Schistosoma haematobium

Sexually transmitted infections

Urethra, vagina, cervix, rectum, or oral pharynx

Direct contact for person-to-person spread

Do not survive in the environment

Asymptomatic people who do not realize that they are infected

Infection with one STI increases the risk for additional STIs

• Viruses
  • HPV, HSV, HBV, HIV
• Bacteria
  • T. pallidum, N. gonorrhoeae, Chlamydia trachomatis
• Fungi
  • Candida species
• Protozoa
  • Trichomonas species
• Arthropods
  • Phthirus pubis

Robbins and Cotran’s Pathological Basis of Diseases

Mother to Baby

• Vertical transmission
  • from mother to fetus or newborn child
• Placental-fetal transmission
  • mother has primary infection with a pathogen during pregnancy
  • Rubella infection during the first trimester can cause heart malformation, mental retardation, cataracts, or deafness in the infant, while little damage is caused by rubella infection during the third trimester
  • congenital syphilis only when T. pallidum infects the mother late in the second trimester but then causes severe fetal osteochondritis and periostitis that leads to multiple bony lesions
• During passage of the neonate through the birth canal
  • gonococcal or chlamydial conjunctivitis
• Maternal milk
  • CMV, HBV, HTLV-1
• Maternal transmission of HIV is a major cause of AIDS in children, mostly occurs during delivery

Zoonotic infections

Animal to human

Direct contact

Consumption of animal products

Indirectly by an invertebrate vector

Nosocomial Infections

• Blood transfusion or organ transplant
• The most common, preventable cause:
  • the hands of healthcare workers
  • from contaminated surfaces such as bedrails
• Methicillin-resistant S. aureus
• Vancomycin-resistant enterococci

References

Robbins Basic Pathology 9 th __ Ed, pp: 315-319__

Robbins and Cotran’s Pathological Basis of Disease 8th Ed, pp: 338-342

Color Atlas of Pathology, pp: 268-285