Infections in the Immunocompromised Host

Question 1

List the 4 types of immunodeficiency.

Answer 1

Neutropenia
Cellular immunodeficiency
Humoral immunodeficiency
Hyposplenism

Question 2

List 5 other risk factors leading to infection in immunodeficiency.

Answer 2

Breakdown of skin barriers
Breakdown of mucosal barriers
Altered microbiome
Impaired nutritional status
Organ dysfunction

Question 3

List 4 causes of neutropenia.

Answer 3

Cytotoxic chemotherapy
Therapeutic irradiation
Steroids
Chronic granulomatous disease

Question 4

List 7 causes of cellular immunodeficiency.

Answer 4

DiGeorge syndrome
Malignant lymphoma
Chemotherapy
Irradiation
Immunosuppressive drugs
Allogenic stem cell transplant
Infections (e.g. HIV)

Question 5

List 4 causes of humoral immunodeficiency.

Answer 5

Bruton agammaglobulinaemia
Lymphoproliferative disorders (e.g. CLL, multiple myeloma)
Radiotherapy
Chemotherapy

Question 6

List 3 common organisms which cause infection in hyposplenism.

Answer 6

Pneumococcus (Strep. pneumoniae)
Haemophilus (H. influenzae type B)
Meningococcus (Neisseria meningitidis)

Question 7

Define neutropenia.

Answer 7

<0.5 x10^9/L

1.0 x10^9/L and falling

Question 8

Describe the pathophysiology of chronic granulomatous disease. (4)

Answer 8

1. Defect in the NADPH oxidase gene, causing defective ROS formation
2. This causes defective intracellular pathogen killing
3. This results in the formation of abscesses throughout the body, e.g.
   a. Lungs
   b. Lymph nodes
   c. Skin
4. This causes widespread inflammatory response
   a. This causes widespread granuloma formation

Question 9

Describe the pathophysiology of neutropenia. (3)

Answer 9

1. Decreased proliferation of haemopoietic progenitor cells
2. This causes depletion of bone marrow reserves
   a. This causes development of neutropenia
3. Neutrophil function is decreased, causing:
   a. Decreased chemotaxis
   b. Decreased phagocytic activity
   c. Decreased intracellular killing

Question 10

What are the consequences of deficient cellular immunity? (1)

Answer 10

Increased susceptibility to infections by:

• Viruses
• Mycobacteria
• Fungi
• Protozoa

Question 11

List 3 common causes of infection in humoral immunodeficiency.

Answer 11

Strep. pneumonia
Haemophilus influenzae B
Neisseria meningitis

Question 12

Briefly describe the normal function of the spleen in immunity. (2)

Answer 12

1. Primary immunoglobulin response: presence of specific antibody needed to opsonise encapsulated bacteria
2. Splenic macrophages phagocytose encapsulated bacteria, e.g.
   - Pneumococcus
   - Haemophilus
   - Meningococcus

Question 13

List 5 normal features of the skin which normally protect against infection.

Answer 13

Desquamates
Dry
pH 5-6
Lower temperature (than inside body)
Secretory IgA in sweat

Question 14

List 2 normal features of mucosal barriers which normally protect against infection.

Answer 14

High mitotic index

Lymphoid tissue

Question 15

Describe the pathophysiology of mucosal barrier breakdown. (3)

Answer 15

1. Disruption of normal mitosis causes inflammatory response in the mucosal lymphoid tissue
2. This causes mucositis, causing:
   a. Pain
   b. Dysphagia
   c. Xerostomia (dry mouth)
   d. Ulceration
3. This impairs GI function by altering mucosal permeability
   a. This can cause deficient nutritional status

Question 16

What causes loss of normal colonisation resistance?

Give 4 examples.

Answer 16

Changes in the normal microbiome, e.g.

• H2 antagonists
• Proton pump inhibitors (PPIs)
• Antibiotics
• Diarrhoea

Question 17

How would you define severe nutritional deficiency? (3)

Answer 17

<75% of ideal body weight
Rapid weight loss
Hypoalbuminaemia

Question 18

Describe how nutritional deficiency causes immunodeficiency. (2)

Answer 18

1. Compromise of integrity of host defences
2. Causes iron deficiency, which further reduces immune function by:
   a. Decreased neutrophil function
   b. Decreased T cell function

Question 19

List 3 causes of organ dysfunction which may cause increased risk of infection.

Answer 19

Tumours
Organ obstruction
Spinal cord compression

Question 20

How does spinal cord compression cause increased risk of infection? (2)

Answer 20

1. Loss of cough/swallow reflex
   a. Pathogens cannot be properly removed from lungs
2. Incomplete bladder emptying
   a. Pathogens aren’t removed from bladder properly

Question 21

How would you define neutropenic fever? (5)

Answer 21

Neutrophil count: <0.5 (OR <1.0 if recent chemotherapy)
Fever/hypothermia: <36 or 38+

SIRS
Sepsis
Septic shock

Question 22

How would you define sepsis?

Answer 22

Evidence of infection, including SIRS

1 of the following, indicating organ dysfunction:

• Hypotension (<100, <60)
• Confusion
• Resp rate 22+

Question 23

How would you define SIRS? (6)

Answer 23

Sweats/chills
Rigors
Malaise
Resp rate 20+
HR 90+
Hypotension

Question 24

How would you define septic shock? (3)

Answer 24

Sepsis induced hypotension requiring inotropic support

OR

Sepsis induced hypotension which does NOT respond to fluid replacement

PLUS

Lactic acidosis