Infection

General Pathology of Infectious Diseases

Dr.Zahraa Osama Yehya
Department of Pathology
Ninevah College of Medicine

Infectious Diseases

INTRODUCTION

Despite medical advances, only a handful of these diseases had actually been defeated, almost all victories are due to immunization programs (e.g. small pox, whooping cough, polio & measles), & thus, these diseases remain important cause of death around the globe, especially in developing countries due to the unsanitary living conditions & malnutrition

Although antibiotic usage has contributed indeed to the taming of some Infectious Diseases, indiscriminate use also has resulted in the development of increasingly virulent, multiple drug-resistant pathogens

The goal of these lectures is to highlight the general mechanisms by which infectious organelles cause pathology, i.e. to know the types, eatiology, pathogenesis, gross & microscopial appearance of these diseases so that we can understand the signs and symptoms, plan therapy, assess prognosis & plan prevention

Definition of infection

Infection is defined as the invasion of living tissue by m.o. or its products, followed by local reaction which may be associated with general reaction

Following invasion, the m.o. may be :

eliminated without causing obvious disease (sub-clinical infection)

or causing clinical disease of any grade of severity

The outcome depends on the complex balance between:
the aggressive mechanisms of the m.o.
& the defense mechanisms of the host

Definitions

Commensals
are microorganisms that live on the expoure of the host WITHOUT causing harm. e.g. bacteria living on the skin, however, these harmless m.o. can cause diseases in case of immunodefeciency, these are called (Opportunistic infections)

Pathogen

m.o. that injure the host, this range from very small prion protein PPr which is 27 kD to 10 meters tape worm


Pathogenicity
the capacity of a particular m.o. to cause disease

Virulence

the degree of pathogenicity

Prions

are modified host protein that can cause human disease like spongiform enchephalopathies as in Creutzfeld-Jacob disease (CJD-mad cow disease).

Routes of Infection

Inhalation
Ingestion
Sexual routes
Parentral e.g. injection , bite etc
transplacental

Factors influencing the infection

1- Microorganism factors
• Access: entry of m.o to the body cells
2. Dose & virulence


3. Invasiveness: ability of m.o to multiply & spread in the body through the use of endotoxin & exotoxin

4. Transmission: ability of m.o to pass to another suitable host.

2-Host Factors:
• Mechanical barriers: clean dry Intact skin, keratin, mucous membrane of the conjuctiva, respiratory & GIT epithelium.
• Chemical forces: acidity of sweat & gastric juice, lysosomal enz. secreted by mucous membrane of the lacrimal, salivary & nasal glands, secretory IgA antibodies in saliva, tears, intestinal contents, respiratory mucous, milk & urine.

• Physical Forces: movement of respiratory cilia, mucus, continuous flow of urine & saliva, increase peristalsis causing diarrhea .
• Phagocytosis: by macrophages & neutrophils.
• Specific immune response: by cell-mediated & humeral immunity.

• Local factors: e.g. ischemia & foreign body promote infection.

• Systemic factors: e.g., malnutrition, diabetes mellitus, chronic alcoholism & malignancy.
• Age: both very young & very old have increasing risk of infection.
• Drugs: appropriate antimicrobial drugs eradicate many susceptible microorganism.

Results of infection

1. Eradication: most infections end by total eradication at the site of entry.


2. Persistence of infection: either in form of carrier state or mild chronic forms e.g. typhoid fever, hepatitis infection.

3. Spread: to other parts of the body .e.g. direct spread as in cellulitis, lymphatic spread as in lymphangitis & lymphadenitis , blood spread as in bactermia, septicemia & pyaemia.

4. Host death: in severe infection e.g. tetanus & diphtheria.

Routs of infection spread inside the body

1- Local spread: by the action of lytic enzymes. e.g Streptococci secrete hyaluronidase enzyme which degrades the extra cellular matrix between host cells.

2- Lymphatic spread: to the Lymph nodes.

3- Hematogenous spread: causing:
-Bacteremia: Presence of m.o in the blood.
-Septicemia: actively multiplying m.o in the blood.

4- Through body fluids: e.g., sexual transmitted disease (gonococcus).

5- Through excretions: e.g., from kidney to lower urinary tract.

6- Through nerves: e.g. rabies virus, varicella zoster virus.

7- Through placental- fetal route.

Tissue response ( microsopical responses) to infections

There are 5 major histological patterns of tissue reaction in infections:
1- Suppurative ( PMN ) inflammation characterized by production of pus .

2- Mononuclear & Granulomatous characterized by interstitial inflammation & formation of granuloma

3- Cytopathic- Cytoproliferative inflammation. These reactions are usually produced by viruses.

4- Necrotizing inflammation caused by powerful toxins e.g. Cl. Perfringens lead to gangrene .

5- Chronic inflammation & scarring, is the final common pathway of many infections, e.g. HBV lead to cirrhosis, Schistosomal eggs lead to fibrosis of U.B. wall

techniques for diagnosis of infectious diseases

H&E stain: e.g. CMV & herpesviruse inclusion bodies, bacterial clumps, candida spp. All protozoa & helminths

Gram stain: for most bacteria

Acid fast stain: for Mycobacteria

PAS (Periodic Acid Shiff): for fungi & ameobae, detect mucin & polysaccharides in m.o. cell wall

Silver stain: for fungi, pneumocystis

Giemsa stain: for Campylobacter, Leishmaniae, Malaria parasites

Culture: for all classes

Molecular diagnostic tests e.g. PCR

Viral Infections

Viruses
are relatively simple, small, obligatory intracellular m.o. which replicates within cells by synthesis and assembly of separate components.

Viruses are classified by their nucleic acid genomes into:

DNA viruses
RNA viruses


Routes of infection

Airborne: m.o. carried by air, direct contact is not needed e.g. measles virus.

Inhalation of respiratory droplets: direct contact is needed ; e.g. influenza, chicken pox, measles, pertusis, RSV.
Ingestion : polio viruses
Parentral (s.c., i.v., i.m.) : e.g. AIDs in drug abuse & blood transfusion
Sexual route: e.g. HIV, HBV
Transplacental: e.g. HIV, HBV, HCV.

Following infection the virus is transmitted by blood cells, along nerves and become localized in certain tissue which it prefer (tropism) e.g. polio, rabies etc

Mechanisms of viral injury

1- Inhibits host cell DNA, RNA or protein synthesis e.g. Poliovirus.

2- Direct cell killing by damaging host cell membrane or DNA e.g. Rhinoviruses.

3. Virus replicate efficiently causing host cell lysis e.g. rhinovirus & influenza

4- Induce Immune reaction e.g type III & IV hypersensitivity reaction in respiratory cyncytial viruses, arbovirus encephalitis.


5- Damage host defence mechanism e.g. respiratory epithelium predisposes to the pneumonia by Staph. Pneumoniae & Haemophilus influenza. Immune system in AIDS.

6- Induce cell proliferation & transformation result in neoplasia e.g. HBV, EBV.

7- Virus killing cells of one type may cause damage to other cells that are dependent on the integrity of the virally damaged cells e.g. Poliovirus kills neurons leading to muscular atrophy.

Microscopical picture of viral infection

Mononuclear infiltration
Tissue necrosis
Giant cell formation
Inclusion body formation. (intranuclear or intracytoplasmic)

Giant cell pneumonia

Measles , RSV , para inlf. V.

Multinuc. Giant cells

HSV

Viral inclusion bodies

viral particles aggregate within the cells they infect & form characteristic ( Inclusion bodies).

Nuclear inclusions surrounded by a clear halo as in Herpes virus

Cytoplasmic inclusions as in small pox and rabies virus
Many viruses do NOT give rise to inclusions e.g. EBV.

Perinuclear clearing & basophilic staining cytoplasmic inclusion bodies (owl’s eye appearance) CMV infection

Body response to viral infection

Lymphocytosis
Production of interferons
Production of neutralizing a.b.s
Cell mediated immunity plays a role in controlling viral infection

Types of viral infection

Aborted.

Latent : Virus is synthesized continuously without altered cell e.g. HBV.

Persistent: Integrated in the cells, reactivated with depressed immunity.

Slow viral infection take very long incubation period as in HIV/AIDS.

Bacterial infections


Classification of Bacteria
Bacteria are classified on several criteria:

Gram stain

Bacteria are accorodingly, of two types:
Gram (+)
Gram (-)

Gram(+): e.g. Staph, Strept, Mycoplasma, Clostridium, Corynebac

Gram (-) Salmonella, Shigella, Pseudomonas, Neisseria, Klebsiella, H.pylori, E.coli

Shape

Bacteria are classified as:
Cocci
Bacilli
Vibrios
Spirochates

Cocci : e.g. Strept, Staph

bacilli (rods) e.g.: Clostridium, Corynebac, Liisteria

• Vibrios e.g: V. cholerae

• Spirochetes e.g. Treponema pallidum (Syphlis)

Growth requirements

bacteria are classified as:
Aerobic
Anaerobic

Mechanism of Bacterial injury(Pathogenesis)

1- Release toxins that kill cells. (exotoxin & endotoxin).

2- Release lytic enzymes, includes proteases, hyaluronidase, coagulase & fibrinolysins that destroy the tissue & facilitate the spread of bacteria .

3- Elicit an inflammatory reaction that may destroy not only the bacteria but also the infected tissue.

4-Elicit an immune reaction that may damage the tissues carrying the same antigen as the bacterium (“cross reactivity”).