General Pathology

Basic Principles of Cellular and Organ

Pathology

Infection - I

Jaroslava Dušková

Inst. Pathol. ,1st Med. Faculty, Charles Univ. Prague

Infection–I – table of contents

Defenses against infection

Interaction of organism and microorganism Bacteriemia (transient)

Sepsis/ Septicemia

Pyemia

Toxemia

Viremia

Bacterial toxins & their action

Host & microorganism encounter

Infection versus disease

Infectious agents of humans – part one

– most important representatives and related pathology

bacteria

fungi

parasites

worms

insects

Inflammation - causes

nonliving

physical

chemical

living

prions

viral

bacterial

mycotic

parasitic

AUTOIMMUNE

Defenses Against Infection – 1.

Surface

– barriers: skin, conjunctiva, mucous membranes

– mechanical removal: shedding, tears, mucus,

ciliary action, coughing, salivation, swallowing,

urination, defecation

– normal bacterial flora

– chemical inhibitors: gastric acid, lactic acid, fatty

acids,bile salts..

– antimicrobial substances: lysozym, secretory IgA

Defenses Against Infection – 2.

Nonspecific resistance factors– fever, interferon, complement, lysozyme, C-reactive

protein, lactoferrin, α1- antitrypsin

Inflammation- soluble factors– clotting system –Hageman fc. (XII)

– complement system: chemotactic fc, anaphylatoxins

– kinin system: bradykinin

Inflammation- phagocytes– circulating: neutrophils, eosinophils, monocytes, macrophages

– fixed: alveoli, spleen, liver, bone marow, brain

Defenses Against Infection – 3.

Immune response

– humoral: B-cells, plasma cells, immunoglobulins

– cell-mediated: T-cells, lymphokins

Interaction of Organism and

Microorganism – Terms

Bacteriemia (transient)

Sepsis/ Septicemia

Pyemia

Toxemia

Viremia

Bacteriemia

transient presence of

microbes in the

bloodstream

Vitium cordis

post

rheumaticum

mitrale

Vitium cordis postrheumaticum

aortale

Sepsis / Septicemia (Severe Bacteremia)

increasing numbers

of microbes (& their toxins)

in the bloodstream

Sepsis/Septicemia

Def.

systemic response to infection

presenting as

tachypnoe > 20/min. tachycardia > 90/min. temperature > 39 st. C. (ev. < 36st.C)

leucocytosis > 15 000/1l (ev. < 4000/1l)

W-F sy

Sepsis – Pathogenetic Factors

Endotoxin, toxins G+

Macrophages

Cytokins

NO

PAF (Platelets

Activating Factor)

TNF, IL–1

TNF, IL–1, IL–6

NO synthesis

vasodilation

coagulation

Syndrome of Systemic Inflammatory ResponseDef.

systemic response to an AGENTmanifestating as

tachypnoe > 20/min. tachycardia > 90/min. temperature > 39 st. C. (ev. < 36st.C)

leucocytosis > 15 000/1l (ev. < 4000/1l)

AGENT : pancreatitis, injury, burns…..

Pyemia

presence of infected

thrombemboli bearing

virulent microbes in the

bloodstream

Endocarditis

bacterialis acuta

Toxemia

presence of microbial

toxin (s) without the

microbes themselves in

the bloodstream

Endotoxin

lipopolysaccharide component

of G- bacteria outer wall

effects: fever, shock, DIC, RDS

effects mediated by IL-1, TNF

DIC& consumption

coagulopathy

Exotoxins -1

often enzymes (leukocidins,

hemolysins, hyaluronidases,

coagulases, fibrinolysins)

others………….

Epidermolytic effect in staphylococcus infection

Neonatal Impetigo - Exfoliatin

Exotoxins -2

diphteria toxin – inhibition of cellular

proteosynthesis

botulotoxin – block of the cholinergic

transmission

choleratoxin – increase in cAMP, losses of

isoosmotic fluid via enterocytes

Host & Microorganism

Encounter

General

Natural

defenses

Inflammation

Immune status

Successful

transmission

Site of attack

Number of microorg.

Pathogenicity

HostGeneral

– age, race, nutrition, other diseases (diabetes)

Natural defenses– skin, mucose integrity

– mucus, cilliary action, unobstructed flow

– protective secretion (lysosym in tears, gastric acid, IgA

Inflammation– leucocytes– macrophages -

phagocytosis

Immune status

– immunity (or lack of it)active, passive

immunisation, contact

– lymphocytes

– immunoglobulins

– complement

Barriers

Microorganism

Successful transmission

Site of attack

Number of microorg.

Pathogenicity invasivenesstoxin productionmultiplicationresistence to host

defence mechanismsability to cause necrosisenzyme release

INFECTION versus DISEASE

Pathogenicity (virulence)

Incubation Period

Carrier State

Agent – Host Interaction

cytocidal

stabilised (steady– state)

transformation –

ONCOGENS

m

W

h

i

p

p

l

e

m.

Whipple

Chlamydia

Inflammation - causes

non

infectious

physical

chemical

infectious

prions (non living, but

transmissible)

viral

bacterial

mycotic

parasitic

AUTOIMMUNE

Infectious Agents of Humans

prions (non living, but transmissible)

viruses (DNA, RNA)

bacteria (incl. chlamydia, mycoplasma,

rickettsia – obligatory intracellular parasites)

fungi (yeasts, molds)

parasites (protozoa, helmints, ectoparasites-

insects: lice, mites, ticks; spiders)

Infectious Agents of Humans Bacteria

simple cells – prokaryotes

both DNA and RNA

cocci, bacilli (AFB!), spirochetes….

Gram positive /negative

extra- and/or intracellular

aerobic/ anaerobic

G+ cocci

Staphylococcus aureus

Staphylococcus epidermidis

Staphylococcus

saprophyticus

Streptococcus α-hemolyticus

Streptococcus β-hemolyticus

Skin: impetigo,

furunculus, carbunculus,

panaritium,

hidradenitis

mastitis

osteomyelitis

pharyngitis

enterotoxicosis

impetigo

tonsilitis, angina

scarlet fever

erysipelas (St. Anthony´fire)

complications: rheumatic fever, glomerulonephritis

Erysipelas - Streptococcus

Impetigo

Acne conglobata

Osteomyelitis purulenta

G+ rods

non-spore forming aerobes

– Corynebacterium diphteriae

– Listeria monocytogenes

– Erysipelothrix rhusiopathiae

spore forming aerobes

– Bacillus anthracis

Diphteria

Listeriosis

Erysipeloid

Anthrax

Laryngitis haemorrhagica et pseudomembranosa

Corynebacterium diphteriae

G- rods Bordetella pertusis

Pseudomonas aeruginosa

Legionella pneumophilla

Brucella abortus, Francisella

tularemiae, Campylobacter

Helicobacter pylori

Escherichia coli

Klebsiella pneumoniae

Salmonella typhi

Shigella dysenteriae

Vibrio cholerae

Haemophillus influenzae,

Ducreyi

Pertussis

respir and urinary inf.

pneumonia

granulomatous, typhoid,

pneumonia

gastritis, ulcers, tumours

urinary inf.

pneumonia

typhoid fever

dysenteria

cholera

pneumonia, ulcus molle

Pneumonia lobaris

Klebsiella pneumoniae

Typhus abdominalis – Salmonella typhi

Typhus abdominalis – Salmonella typhi

Typhus abdominalis – Salmonella typhi

Typhus abdominalis – Salmonella typhi

Lymphogranuloma venereum -inguinale

G- Cocci

Neisseria gonorrhoeae

Neisseria meningitidis

Gonorrhoea

Meningitis

Meningitis purulenta - Neisseria

CSF

Neisseria gonorrhoeae

Anaerobic bacteria

non-spore forming anaerobs

– Actinomyces israeli G+

– Fusobacterium G-

spore forming anaerobs G+

– Clostridium tetani

– Clostridium botulinum

– Clostridium perfringens,

septicum, histolyticum

– Clostridium difficile

Actinomycosis

cellulitis

Tetanus

Botulismus

Gangrene

pseudomembranous

colitis

Colitis pseudomembranosa - Clostridium difficile

Infectious Agents of Humans Fungi

complex cells – eukaryotes

both DNA and RNA

yeasts, molds (hyphae, pseudohyphae…)

PAS, impregnation

extra- or intracellular

mostly opportune pathogens

Candida esophagitis

Candidiasis

Pneumocystis carinii pneumonia

silver methenamine

Pneumocystis carinii

Infectious Agents of Humans Parasites -1

Protozoa

complex cells – eukaryotes

both DNA and RNA

extra- or intracellular

(Amebas, Trichomonas,Trypanosoma,

Toxoplasma, Plasmodium, Pneumocystis…)

Trichomoniasis

Toxoplasmosis

Toxoplasmosis cerebri cyst

Toxoplasmosis cerebri

microcephallus

microphtalmus

deafness

palsies

Infectious Agents of Humans Parasites -2

Metazoa (helmints and flukes)

multicellular

both DNA and RNA

flat and round worms

extracellular

(Taenia, Ascaris, Enterobius, Trichuris

Echinococcus, Clonorchis, Schistosoma,

Wuchereria…)

Trichinosis

Ascaris lumbricoides - Roundworm

Trichuriasis (whipworms)

Wuchereria bancrofti (microfilariae)

Cystis

parasitaria

hepatis

(Echinococcus)

Schistosomiasis

Ca spinocellulare vesicae urinariae

Oxyuriasis

Infectious Agents of Humans Parasites -3

Insecta, Arachnida

multicellular

both DNA and RNA

extracellular

(Sarcoptes scabiei, fleas, ticks, lice……)

Sarcoptes scabiei

Pediculus humanis capitis (head louse)

Phthirius pubis (pubic louse – crab louse )

The tick-borne diseases

Babesiosis (a malaria-like infection Babesia microti)

Ehrlichiosis (rickettsia Ehrlichia canis)

Lyme disease (Borelia Burgdorferi)

Rocky Mountain spotted fever (Rickettsia rickettsi)

Tularemia (rabbit fever Francisella tularensis )

Tick paralysis (virus a member of the family Flaviviridae)