General pathology of infectious diseases. A45-A49

Question 1

A/45. Categories of infectious agents

What are the 8 categories? breif description.

Answer 1

Prions -

• Transmissible abnormal forms of proteins
• Accumulate in neurons and cause neurological disease.
• The altered structural form causes them to be protease resistant and act as a nucleation site for other abnormal proteins to form.
• Bovine spongiform encephalopathy. Component of Alzheimer’s

Viruses

• organisms that require other cells to replicate and transcribe DNA/RNA
• DNA or RNA genome
• Protein Capsid
• Sometimes, a Lipid Envelope which may contain envelope proteins. (gp120 and gp41 in HIV)

Bacteriophages, plasmids, transposons

• These can all incorporate into the genome of bacteria.
• After bacterial incorporation, they can then cause diseases in humans
• Transposons can express reverse transcriptase or express proteins which move the physical dna to a new location, so they can then directly infect human cells as well.
• Plasmids are exchanged between bacteria, and can confer new virulence or resistance between them.

Bacteria

• Bacteria
• ATP-parasite bacteria -> chlamydia, rickettsia, obligate intracellular, somewhere in between bacteria and viruses.

Fungi

• Are eukaryotes
• Grow as budding yeasts or slender hyphae
• Cell wall chitin
• Candida is a fungus
• Yeast infections, UTIs
• Aspergillus
• Usually infect immunocompromised patients
• Often cause superficial infections of the nails, skin, hair.

Protozoa

• ​Single-celled eukaryotes
• Plasmodium - Malaria
• Trichomonas - an STD causing urinary tract infection, often asymptomatic.

Helminths

• Multicellular parasitic worms.
• Humans are usually only one part of their life cycle.
• Pathologies are usually because of the inflammatory response to the eggs or larva
• Roundworms. non-segmented
• Flatworms, segmented worms with no gut that absorb nutrients through their thin surface
• Flukes primitive worms that are wide and leaf shaped, their integument aka “skin” is made of a single syncitium of fused cells.

Ectoparasites

• parasitic insects
• fleas
• lice
• ticks
• mites
• spiders

Question 2

A/46. Transmission of microbes

Routes of infection

Barriers to infection

Answer 2

Routes of infection

1. Inhalation
2. Ingestion
3. Sexual transmission
4. Bites
5. Injection
6. Direct skin contact

Barriers:

1. Skin.
   
   • Low pH 5.5 or less,
   • Dense, keratinized tissue
   • High fatty acid content also inhibits microbial growth.
   • Very few organisms can penetrate unbroken skin, Schistosoma larvae are the example.
   • Penetrated by physical breaks, or iatrogenic breaks.
   • Insect bites
2. Mucosa surfaces
   
   • ​​Lactoperoxidase
   • Lysozyme
   • Natural antibodies
   • IgA antibodies
   • Defensins - pore forming molecules that embed into many microbes
3. GI tract
   
   • ​​Gastric acid
   • Mucous covering
   • Digestive enzymes lysing the pathogens
   • Normal flora competition, protection
4. Respiratory tract
   
   • ​​Ciliary epithelium movement.
   • Mucous coating
   • High numbers of alveolar macrophages and neutrophils.​
5. Urogenital tract
   
   • ​​Usually invaded through the urethra
   • Regular flushing of the fluid by urination is a good defense
   • The shorter urethra for women gives them higher risk for UTIs

Question 3

A/46. Transmission of microbes

Phases of transmission, from entry to exit

Answer 3

1. Entry, via the skin, respiratory tract, GI, or urogenital tract
2. Dissemination
   
   • Lytic enzymes or physical penetration of the tissue
   • Dissemination via the blood or lymphatics
   • Local spread by replication and release
   • Some viruses can spread along nerve fibers.
3. Release from the body
   
   • Any secreted fluid or lost cells can spread the microorganisms
   • Skin shedding
   • Saliva, spit
   • Respiratory droplets
   • Oral-fecal spread
   • Blood exposure
   • Direct contact
   • Sexual contact
   • Vertical transmission, maternal-child transmission
   • Transmission via mothers milk, heptatis B virus, cytomegalovirus
   • zoonotic transmission from animals to humans
   • vectoral transmission via insects.

Question 4

A/47. How microorganisms cause disease

Viruses

Answer 4

The tissue tropism of a virus (the particular cells that it infects) is determined by the viral receptors expressed on the cells.

Viral injury mechanisms:

1. Inhibiting normal protein synthesis by the host cells, due to their hijacking
2. Production of degradative enzymes or toxic proteins
3. Inducing apoptosis of the infected cells, from the cells intrinsic response, or from the subsequent inflammatory response.

Question 5

A/47. How microorganisms cause disease

Bacteria

Answer 5

​Bacterial injury mechanisms:

1. Virulence factors.
   
   • Ahesins,
   • Hemolysins
   • Toxins
   • Superantigens
2. Plasmids, transposons, bacteriophage elements may be carried by the bacteria, coding their own virulence factors
3. Biofilm formation - creating favorable environment for bacterial growth, impeding immune access.
4. Cell apoptosis of intracellular bacteria
5. Endotoxins
   
   • ​​LPS
6. Exotoxins
   
   1. Enzymes
   2. Superantigens
   3. Neurotoxins - cleave vesicular proteins of specific neurons - botulinum toxin tetanus toxin.
   4. Enterotoxins, ion channel activators, adenylate cyclase activators
7. Immune system induced damage
   
   1. Granulomatous reaction
   2. Tissue damage and apoptosis
   3. Post-infection fibrosis
   4. Post-streptococcal diseases,
      
      1. Molecular mimicry causing Rheumatic fever endocarditis and valve damage.
      2. Immune complex deposition causing glomerulonephritis.
      3. Chorea
         Arthritis
         Nodules
         Carditis
         Erythema Marginatum
         Rheumatic Fever
   5. Chronic inflammation due to chronic infection increases the risk of cancer.

Question 6

A/48. Technigues for diagnosing infectious agents

Answer 6

1. Clinical presentation,
2. Patient history and potential exposures
3. Specimen collection
4. Culturing the sample
5. Staining of the sample with general stains, specific immunostains.
6. Biopsy
7. Cytology
8. Serology
9. PCR analysis
10. Immunostaining of the sample

Question 7

A/49. Sepsis and perinatal infections

Sepsis:

Symptoms, Risk factors, Treatment

Answer 7

Definition: Systemic, whole body inflammation, caused by an infection.

Diagnosis: Two of the Systemic inflammatory response syndrome criteria, along with a presumed/known infection.

1. Body temperature above 38 or below 36C
2. Heart rate above 90bpm
3. Breathing rate above 20 bpm
4. paCO2 less than 32mmHg
5. leukocytosis, WBC count more than 12x10⁹
6. WBC depletion, WBC less than 4x10⁹ or

Symptoms:

1. Fever,
2. Tachycardia
3. Tachypnea
4. Confusion
5. Symptoms related to the specific infection
6. Septic shock

Risk factors:

1. Compromised immune system, from:
2. Old age
3. Chronic debilitating diseases,
4. Diabetes
5. Cancer
6. AIDS
7. Major trauma or burns
8. Malnutrition, Malabsorption syndrome
9. Third trimester of pregnancy
10. Immune suppression drugs
11. Old age
12. Infants, (very young immune system)

Treatment:

1. IV fluids and antibiotics
2. Treat the infectious agent.
3. Blood pressure drugs to manage it if IV fluids don’t help.
4. Dialysis and mechanical ventilation if neccessary

g) Treatment: blood cultures should be done before treatment with antibiotics (infection of the blood
is not necessary for diagnosis).
i. Main treatment is with IV fluids and antibiotics. If this cannot raise blood pressure, drugs
are given to increase BP.
ii. If necessary mechanical ventilation and dialysis can be given to support failing lungs and
kidneys.

Question 8

A/49. Sepsis and perinatal infections

Perinatal infections. What are the most frequent infections (hint, acronyms)

How are perinatal infections aquired?

Answer 8

They are infected either transplacentally or by vaginal contact/blood contact during birth. Or by contact in the environment very soon after birth.

TORCH:

• Toxoplasma
• Other
• Rubella
• Cytomegalovirus
• Herpes Simplex virus

SIKE, that acronym old. Its actually: CHEAPTORCHES

• Chickenpox, Shingles
• Hepatitis (b, c, d, e)
• Enteroviruses
• AIDS
• Parvovirus B19
• Toxoplasma
• Other
• Rubella
• Cytomegalovirus
• Herpes simples
• Every other STD
• Syphilis

Other:

• Group B streptococcus. (Streptococcus agalactia - meningitis in infants)
• Listeria - also meningitis
• Candida
• Coxsackievirus
• Chlamydia
• Lyme disease