Infectious pathology - BSMU

Infectious pathology

Ivan Sakharau, assist. lect.

General principles

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1. Each infection has its agent, which can be found in blood or excreta

2. The agent has site of entry specific to each infection

3. Inflammation in the site of entry is called “primary affect”. Spreading of the infection leads to envolvement of lymph vessels (lymphangitis) and lymph nodes (lymphadenitis)

The combination of primary affect , lymphangitis and lymphadenitis is called “primary complex”

General principles

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4. Agent spreads from primary affect or complex by lymphatic , hematogenous , intracanalicular , perineural or contact ways

5. Each infectious disease is characterized by local changes that develop in a particular tissue or organ…

(colon in dysentery, walls of small blood vessels in typhus etc.)

… and to some extent are typical for the disease.

General principles

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6. Infectious diseases are accompanied by common changes: skin rash, vasculitis, hyperplasia of the lymph nodes, spleen, bone marrow, inflammation in interstitial tissue, degenerative changes in parenchymal organs

7. Infectious diseases often occur in cycles:

incubation

prodromal period

period of the main manifestations

8. Outcomes: recovery, residual effects after complications, chronization , carrier state, death

Categories of infectious agents

Prions

Viruses

Bacteria

Chlamidiae, Rickettsiae, Mycoplasmas

Fungi: Yeasts, Hyphae

Parasites: Protozoa, Worms, Arthropods

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Classes of Human Pathogens and Their Habitats

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Taxonomic Size Site of Propagation Sample Species Disease

Viruses 20–300 nm Obligate intracellular Poliovirus Poliomyelitis

Chlamydiae 200–1000 nm Obligate intracellular Chlamydia trachomatis Trachoma, urethritis

Rickettsiae 300–1200 nm Obligate intracellular Rickettsia prowazekii Typhus fever

Mycoplasmas 125–350 nm Extracellular Mycoplasma pneumoniae Atypical pneumonia

Bacteria 0.8–15 µm Cutaneous Staphylococcus aureus Wound

Mucosal Vibrio cholerae Cholera

Extracellular Streptococcus pneumoniae Pneumonia

Facultative intracellular Mycobacterium tuberculosis Tuberculosis

Fungi 2–200 µm Cutaneous Trichophyton sp. Tinea pedis (athlete's foot)

Mucosal Candida albicans Thrush

Extracellular Sporothrix schenckii Sporotrichosis

Facultative intracellular Histoplasma capsulatum Histoplasmosis

Protozoa 1–50 µm Mucosal Giardia lamblia Giardiasis

Extracellular Trypanosoma gambiense Sleeping sickness

Facultative intracellular Trypanosoma cruzi Chagas disease

Obligate intracellular Leishmania donovani Kala-azar

Helminths 3 mm–10 m Mucosal Enterobius vermicularis Enterobiasis

Extracellular Wuchereria bancrofti Filariasis

Intracellular Trichinella spiralis Trichinosis

Viruses

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Less than ½ micron, usually much less

DNA/RNA “core” (genome)

Protein “capsid” (protein “coat”)

Sometimes a lipid “envelope”

Limited number of genes coding for all other structures

No consistent naming system

Bacteria

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Gram staining with crystal violet

POSITIVE: thick wall, one phospholipid layer

NEGATIVE: thin wall, two phospholipid layers

Shape

Cocci (balls)

Bacilli (rods)

Oxygen requirements

Aerobic (need O2)

Anaerobic (do not need O2)

“Facultative” aerobic, makes ATP if O2 is present.

Bacteria

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Bacteria

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Chlamydiae, Rickettsiae, Mycoplasmas

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Like Bacteria, but…..

No cell wall (mycoplasma)

No ATP (chlamydia)

No life outside a cell (obligate intracellular, rickettsiae)

Fungi

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Yeasts, hyphae

The most prevalent is Candida

Dermatophytes (superficial)

Epidermophyton

Trichophyton

Microsporum

Deep fungi (granulomas)

Histoplasmosis

Blastomycosis

Coccidiomycosis

Yeasts and hyphae

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Parasites

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Single-celled

Protozoa

Multi-celled

Helminths

“Ecto”-parasites, i.e., Arthropods

Agent and host interaction

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An infectious agent may… fail to infect a person

produce asymptomatic infections

cause symptomatic disease

produce lethal (deadly) infection

Symbiosis (relationship between individuals of different species where both individuals benefit)

Commensalism (one organism benefits without affecting the other)

Parasitism (one organism benefits at the expense of the other)

Transmission

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Skin contact

Coughing/sneezing

Urine

Feces

Blood

Vectors, e. g., insects

“STDs” (sexually transmitted diseases)

Infectivity, general

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Agent → host cell

Agent → toxins → necrosis

Agent → host cellular reaction → damage/death

Infectivity, viral

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Attachment

Entry

Transcription

Translation

Result:

Inclusions

Reduced host cell function

Cell injury, lysis, death

Neoplasm

Infectivity, bacterial

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Adherence

Entry

Toxins

Endo (bacterial components (LPS)) Gram -

Exo (secreted proteins) Gram -/+,

Host Defense Mechanisms

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Skin

Tears

Normal bacterial flora

Gastric acid

Bile

Salivary and pancreatic secretions

Mucociliary blanket

Secretions e.g. bronchial secretion

Immune system (e.g. neutrophils, monocytes)

Cellular host responses

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Suppurative

Infiltration or exudate with numerous neutrophils

Mono-nuclear

Infiltration lymphocytes, macrophages (i. e., Monocytes)

Granulomas – specific response

Fibrosis

Hemosiderin

Calcification

Cellular host responses

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Dysentery (Shigellosis)

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Necrotizing infection of the distal small bowel and colon

Four species of Shigella

Shigella boydii

Shigella dysenteriae

Shigella flexneri

Shigella sonnei

Aerobic gram-negative rods

S. dysenteriae is the most virulent

Typically presents with abdominal pain and bloody, mucoid stools

Dysentery (Shigellosis) – Epidemiology

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Spread from person to person by the fecal-oral route

No animal reservoir

Infection usually occurs through ingestion of fecally contaminated food or water, but it can be acquired by oral contact with any contaminated surface

Endemic shigellosis is more common in populations with poor standards of hygiene and sanitation

Shigellosis is also spread in closed communities, such as hospitals, barracks, and households

In developed countries, S. flexneri and S. sonnei are more common, and infection tends to be sporadic

Dysentery (Shigellosis) – Pathogenesis

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Disease is produced by ingestion of as few as 10 to 100 organisms

The agent proliferates rapidly in the small bowel and attaches to enterocytes, where it replicates within the cytoplasm.

Replicating Shigellae kill infected cells then spread to adjacent cells and into the lamina propria.

Shigellae produce a potent exotoxin (Shiga toxin) that inhibits protein synthesis…

…and causes watery diarrhea, probably by interfering with fluid absorption in the colon

Shigellae extensively damage the epithelium of the ileum and colon, they rarely invade beyond the intestinal lamina propria, and bacteremia is uncommon.

Dysentery (Shigellosis) – Pathology

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The distal colon is almost always affected, although the entire colon and distal ileum can be involved

The affected mucosa is edematous, acutely inflamed, and focally eroded

Ulcers appear first on the edges of mucosal folds, perpendicular to the long axis of the colon

A patchy inflammatory pseudomembrane, composed of neutrophils, fibrin, and necrotic epithelium, is commonly found on the most severely affected areas

Regeneration of infected colonic epithelium occurs rapidly, and healing is usually complete within 10 to 14 days


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Cholera

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Vibrio cholerae, an aerobic, 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

Cholera

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Cholera hospital in Dhaka, Bangladesh

Cholera

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Typical "rice water" diarrhea – up to 20 liters per day

Cholera – Epidemiology

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Seven pandemics since XIX century

Occurs mainly in the developing world

Cholera affects an estimated 3–5 million people worldwide, and causes 58,000–130,000 deaths a year as of 2010

In the early 1980s, death rates are believed to have been greater than 3 million a year

Cholera remains endemic in the river deltas of India and Bangladesh, where it may cause up to a half-million deaths annually.

Cholera – Epidemiology

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It is acquired by ingesting V. cholerae, primarily in contaminated food or water

Epidemics spread readily in areas where human feces pollute the water supply.

Shellfish and plankton may serve as a natural reservoir for the organism

Cholera – Pathogenesis and Pathology

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Bacteria that survive passage through the stomach thrive and multiply in the mucous layer of the small bowel

They do not themselves invade the mucosa but cause diarrhea by elaborating a potent exotoxin, cholera toxin.

The toxin enters the cell, where it activates adenylyl cyclase. The consequent rise in cell cyclic adenosine monophosphate (cAMP) content results in massive secretion of sodium and water by the enterocyte into the intestinal lumen

The greatest fluid secretion occurs in the small bowel

Cholera – Pathogenesis and Pathology

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V. cholerae causes little visible alteration in the affected intestine, which appears grossly normal or only slightly hyperemic

Microscopically, the intestinal epithelium is intact but depleted of mucus.

Cholera – Stages

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Enteritis

serous or sero-hemorrhagic inflammation

edema of mucosa

hypersecretion of goblet cells

Gastroenteritis

desquamation of intestinal epithelial cells

serous or sero-hemorrhagic gastritis

progressive dehydration (diarrhea and vomiting)

Cholera – Stages

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Algid

marked congestion, edema, necrosis and sloughing of the epithelial cells

mucosal infiltration by lymphocytes, plasma cells, neutrophils

foci of hemorrhage

distended bowel loops contain large amount (3 - 4 liters) of a colorless, odorless liquid

serosa of intestines is dry and sticky with dot hemorrhages

Cholera – severe dehydration

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Rigor mortis occurs quickly and persists for several days

As a result, the muscle contour is seen

The skin is dry, wrinkled, particularly on fingers

Mucous membranes, subcutaneous tissues, muscles are dry

Blood in veins is jelly-like and dark

Severe dystrophic changes in organs

Cholera – Dehydratation

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Meningococcal infection – Epidemiology

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Neisseria meningiditis, Gram-negative cocci

Meningococci spread from person to person, primarily by respiratory droplets

About 5% to 15% of the population carries the organism as a commensal in the nasopharynx

Meningococcal diseases appear as sporadic cases, clusters of cases and epidemics

Most infections in industrialized countries are sporadic and afflict children under the age of 5

Epidemic disease occurs most frequently in crowded quarters, such as among military recruits in barracks

Meningococcal infection – Pathogenesis

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N. meningitidis attaches to nonciliated respiratory epithelium by means of its pili.

Most exposed persons then develop protective bactericidal antibodies over the following weeks, and some become carriers.

If the organism spreads to the bloodstream before the development of protective immunity, it can proliferate rapidly in unprotected human tissue, resulting in fulminant meningococcal disease.

Meningococcal infection – Pathogenesis

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Many of the systemic effects of meningococcal disease are due to the endotoxin of the outer membrane lipopolysaccharide of the bacterium

Endotoxin promotes a conspicuous increase in activation of the complement and coagulation cascades

This leads to disseminated intravascular coagulation, fibrinolysis, and shock

Meningococcal infection – Clinical classification

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1. Localized forms: carrier state

meningococcal nasopharyngitis

2. Generalized forms: meningococcemia

meningitis

meningoencephalitis

a mixed form (meningitis and meningococcemia)

3. Rare forms: arthritis

myocarditis

pneumonia

Meningococcal infection – Meningococcemia

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Diffuse damage to the endothelium of small blood vessels

Small bleeds into the skin cause the characteristic petechial rash

Rash appear with the “star-like” shape. This is due to the release of toxins into the blood that break down the walls of blood vessels.

A rash can develop under the skin due to blood leakage that may leave red or brownish pin prick spots

DIC can cause ischemic tissue damage: Waterhouse-Friderichsen syndrome (hemorrhagic necrosis of

adrenal glands)

Symmetrical cortical necrosis in kidneys


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Meningococcal infection – Meningitis

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First 2-3 days – serous inflammation and hyperemia of meninges, then suppurative

Inflammation begins on the basal surface of brain and extends to cerebral hemispheres through perivenous space (“green cap”)…

… and to meninges of spinal cord

Ependyma and choroid plexus may also be involved developing purulent ependimatitis and pyocephaly (more common in children during the first 2 - 3 years of life)

Micro: blood vessels of the pia mater are congested, subarachnoid space is filled with numerous leukocytes and fibrin strands .


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Diphtheria – Epidemiology

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Corynebacterium diphtheriae, aerobic, pleomorphic, gram-positive rod

Humans are the only known reservoir for C. diphtheriae, and most persons are asymptomatic carriers

The organism spreads from person to person in respiratory droplets or oral secretions

Years ago, diphtheria was a leading cause of death in children 2 to 15 years of age, but immunization programs have largely eliminated the disease

Diphtheria persists as a major health problem in less-developed countries

Diphtheria – Pathogenesis

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C. diphtheriae enters the pharynx and proliferates, often on the tonsils

Diphtheria toxin is absorbed systemically and acts on tissues throughout the body, with the heart, nerves, and kidneys being most susceptible to damage

Diphtheria toxin is one of the most potent known, and one molecule suffices to kill a cell

Not all strains of C. dipheriae produce exotoxin. The gene encoding the exotoxin is carried by a bacteriphage, lysogenic beta phage

Diphtheria – Classification

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1. Diphtheria oropharynx:

localized –catarrhal or fibrinous inflammation;

generalized – lesions outside the oropharynx;

subtoxic, toxic (I, II and III), hypertoxic.

2. Diphtheria croup:

localized – diphtheria of larynx;

spread – diphtheria of larynx and trachea;

descending – diphtheria of the larynx, trachea, bronchi.

3. Other sites:

diphtheria of the nose, eyes, skin and genitals.

4. Combined forms

Diphtheria – Pathology

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The characteristic lesions of diphtheria are the thick, gray, leathery membranes composed of sloughed epithelium, necrotic debris, neutrophils, fibrin, and bacteria that line affected respiratory passages (from the Greek, διφθέρα (diphthera) “pair of leather scrolls”)

The epithelial surface beneath the membranes is denuded, and the submucosa is acutely inflamed and hemorrhagic

The inflammatory process often produces swelling in the surrounding soft tissues, which can be severe enough to cause respiratory compromise

When the heart is affected, the myocardium displays fat droplets in the myocytes and focal necrosis

In the case of neural involvement, the affected peripheral nerves exhibit demyelination


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Infectious pathology - BSMU