PBL 28

Question 1

Pathophysiology of pneumonia

1. Mechanism
2. Symptoms
3. Risk factors
4. Microbiology

Answer 1

1. Mechanism
   - Bacteria enter the lung by inhalation
   - Bacteria live in the upper respiratory tract and are continuously being inhaled into the alveoli
   - Once inside the alveoli, bacteria travel into the spaces between cells and between adjacent alveoli through connecting pores
   - Bacteria trigger an immune response to send neutrophils to the lungs
   - Neutrophils and macrophages engulf and kill the bacteria, and neutrophils release cytokines that result in the activation of the immune system (fever, chills fatigue)
   - Neutrophils, bacteria, and fluid leaked from surrounding blood vessels fill the alveoli and result in impaired O2 transport
   - Bacteraemia (bacteria in blood) can result in serious illness such as sepsis and eventually septic shock
   - Bacteria can also travel into the pleural cavity and cause pleurisy
2. Symptoms
   - Coughing, may be dry or thick yellow, or blood tinged (due to lung infection)
   - Difficulty breathing/shortness of breath (alveoli damage)
   - Increased heart rate
   - High temperature
   - Sweating and shivering (activation of immune system)
   - Loss of appetite
   - Chest pain
3. Risk factors
   - Babies
   - Elderly people
   - Smokers
   - People with other health conditions (asthma, CF, heart/kidney/liver conditions)
   - Immunocompromised people
4. Microbiology
   - Streptococcus pneumoniae: G+ve & most common cause of community acquired pneumonia. Part of the normal respiratory tract flora
   - Staphylococcus aureus: G+ve
   - Streptococcus agalactiae: G+ve - common cause in 0-2month old patients

Question 2

Pathophysiology of meningitis

1. Mechanism
2. Symptoms
3. Risk factors
4. Treatment
5. Microbiology/Causes

Answer 2

1. Mechanism
   - Bacteria reaches the meninges through the bloodstream or direct contact between the meninges and either the nasal cavity or skin. This is often preceded by viral infections, which break down normal barrier provided by the mucous surfaces
   - Once the bacteria has entered the bloodstream, they enter the subarachnoid space in places where the blood-brain-barrier is vulnerable (e.g choroid plexus)
   - Large scale inflammation occurs in the subarachnoid space due to the response of the immune system to the entry of bacteria into the CNS
   - The astrocytes and microglia identify the bacteria and release cytokines that recruit other immune cells
   - The BBB becomes more permeable leading to vasogenic cerebral oedema
   - The walls of the blood vessels themselves become inflamed (cerebral vasculitis), which leads to decreased blood flow and cytotoxic oedema
   - The 3 forms of oedema lead to increased intracranial pressure. This coupled with the lower BP means it is harder for blood to enter the brain, the brain cells become deprived of oxygen and undergo apoptosis
2. Symptoms
   - Fever
   - Headache
   - Neck stiffness
   - Confusion
   - Inability to tolerate light
   - Vomiting
   - Rash
3. Risk factors
   - Skipping vaccinations
   - Age: most cases younger than 5
   - Living in a community setting
   - Pregnancy
   - Compromised immune system
4. Treatment
   - IV antibiotics
   - IV fluids
   - Oxygen through face mask
   - Viral meningitis tends to get better alone within 7-10 days
5. Microbiology/Causes
   - Most commonly caused by viral infections, then bacterial, and rarely fungal and parasitic

• 0-3 months = Group B streptococci, E.Coli, listeria monocytogenes
• Older children = Neisseria meningitidis (meningococcus & teenagers/young adults), streptococcus pneumoniae
• Adults = Neisseria meningitidis, streptococcus pneumoniae, listeria monocytogenes (found in unpasteurised cheeses, hot dogs and lunch meats. Most susceptible to pregnant women, newborns, older adults and immunosuppressed people)
• Viral causes:
  1. Enteroviruses
  2. Herpes simplex virus
  3. VZV
  4. Mumps virus
  5. HIV

Question 3

Pharmacology of cephalosporins

Answer 3

• Bactericidal
• Same mechanism as beta-lactams
  Disrupt the synthesis of the peptidoglycan layer forming the bacterial cell wall. PBPs (transpeptidases) bind to D-Ala-D-Ala at the end of peptidoglycan precursors to crosslink the peptidoglycan & cephalosporins mimic the D-Ala-D-Ala site, thereby irreversibly inhibiting PBP crosslinking of peptidoglycan
• 1st generation cephalosporins = G+ve
• 2nd generation cephalosporins = G-ve