L13 - Lung of immunocompromised patient Flashcards
Innate defences
mucociliary, neutrophils and macrophages
adaptive defences
B cells, T cells
Cystic fibrosis
autosomal recessive disease causes mutations
defective exchange of chloride leads to extracellular dehydration with excessive thick sputum, infection and severe bronchiectasis
CF type I
no protein produced
CF type 2
protein produced but not transported to the cell membrane
CF type 3
protein transported to cell membrane but does not work properly
CF type 4
gets to cell membrane and functions, but is less effective than the WT
CF type 5
less proteins produced that make it to the cell membrane
CF type 6
less stable proems produced so many don’t make it to the cell membrane
Ivacaftor
potentiates channel open probability, improvements in lung function, nutrition and CFTR function
HIV
lenti/retrovirus that infects cells via CD4 receptors and co-receptors on T helper cells, macrophages and dendritic cells
AIDS
Occurs when viral replication kills the infected cells
HIV drug resistance
replication is error prone therefore mutations arise that induce resistance
HIV mechanism
glycoproteins on HIV allow it to dock and fuse to CD4 and CCR5 receptors
viral capsid enters the cell, enzymes and nucleic acids are released
Using reverse transcriptase ssRNA is converted to dsRNA
Viral DNA is then integrated into the cells own DNA by integrase enzyme
When infected cell divides, viral DNA is read and viral proteins are made
innate virus leaves the cell, taking the cell membrane with it
undergoes maturation
HIV maturation protein chains
in the new viral particle are cut by the protease enzyme into individual proteins that combine to form a working virus
ARVs
work by interfering with virus replication by preventing HIV docking and interfering with action of the major HIV enzymes
major HIV enzymes
reverse transcriptase, integrase and protease
Fusion inhibitor drugs
Enfurvitode, T-20
Miraviroc
CCR5 receptor blocker
NNRTI
non-nucleotide reverse transcriptase inhibitor
Efavirennz
NNRTI
Nervirapine
NNRTI
Rilpivirine
NNRTI
NRTI
Nulceotide reverse transcriptase inhibitor
3TC Lamivudine
NRTI
FTC Emtricitatine
NRTI
AZT Zidovurine
NRTI
TDF Tenofovir
NRTI
ABC Abacavir
NRTI
Dolutegravir
integrase inhibitor
Raltegravir
integrase inhibitor
Elvitegravir
integrase inhibitor
Dorunavir
protease inhibitor
Atazanavir
protease inhibitor
Lopinavir
protease inhibitor
HAART
HIV treatment. comprises of combinations of 3 different ARVs, using two NRTIs plus either another NNRTI, protease inhibitor or integrase inhibitor
HAART benefits
recommended for all patients as it reduces transmission and increases life expectancy
HAART problems
many tablets for life, complex for patients, missed doses encourage treatment failure and resistance, many side effects
B cell defects and antibody deficiency
particularly associated with CVID and anti-CD20 monoclonal antibody therapy and other immunosuppression
increased risk of encapsulated bacteria and oto-sino-pulmonary infection
Primary antibody deficiency
immunoglobulin replacement has dramatically increased survival, reduces infections including pneumonia
secondary antibody deficiency
immunoglobulin replacement indications are less clear, only might be used
Immunoglobulin replacement
prepared from pooled plasma from healthy donors, can be administered by intravenous and subcutaneous lifelong
Infection prophylaxis
prophylactic agents need to be taken continuously
decision to institute prophylaxis depends on many factors…
nature and severity of underlying condition, risk of infection, previous infection history, evidence it will benefit situation, availability of agents, route, frequency and side effects, treatment burden, antimicrobial stewardship
Antibiotic prophylaxis
used in myelotoxic chemotherapy with neutropenia, can be predicted in both time and severity
Antibiotic and anti fungal prophylaxis
in chronically neutropenic patients, e.g. bone marrow transplant or those with inherited defects
Pneumocystic pneumonia prophylaxis
used in HIV and immunosuppression
Pneumocystic pneumonia
life-threatening opportunistic lung infection of immunocompromised individuals
Pneumocystic pneumonia cause
by pneumocystis jinvecii, a fungus with some protozoal features
Pneumocystic pneumonia occurs in..
patients with reduced Th cell number of function, e.g. HIV, chronic high dose steroids, solid organ or bone marrow transplantation
Co-trimoxazide
Oral
inhibit folate biosynthesis
rashes, bone marrow suppression and GI problems,
extremely effective
Nebulised pentamidine
Nebulised monthly
uncertain mode of action, anti-parasitic,
cough, bronchospasm and need to protect staff
effective but some failures
pulmonary infection presentation in immunocompromised patients
may be non-specific
chest X-ray or CT, blood tests
investigation of sputum samples
PCP
fungus with some protozoan features, usually killed by alveolar macrophages, requiring CD4+ activated Th cells
progressive breathlessness and dry cough with ground glass opacity on CTs
PCP treatment
high dose co-trimoxazole
toxicity: fluid load, rash, renal/liver toxicity, low blood K+, neutropenia and low blood glucose
Adjunctive corticosteroid therapy for moderate to severe PCP enhances survival in HIV - reduces inflammation to dying organisms
Invasive aspergillosis
environmental fungus affecting neutropenic or immunocompromised patients
can be progressive and fatal
pulmonary nodules or infiltrates on CT
Echinocandins
inhibit synthesis of B glycans
Trizoles
inhibit lanosteol-14a-demethylase, which converts lanasterol into ergosterol
Polyenes
bind ergosterol to weather the membrane and make i t’leaky’
Invasic aspergillosis treatments
echinocandins, amphatericin B and nephrotoxic
Echinocandins side effects
well tolerated but there is GI disturbance, hepatotoxicity, allergic reactions, not very effective alone
Amphotericin B
IV only but lipsomal formulation to reduce toxicity
Neprhotoxic
hypokalaemia, chills and allergic reactions
Voricanazole
fist line invasive aspergillosis treatment
reduces immunosuppression
oral or intravenous
Voricanazole side effects
visual disturbance, cardiac rhythm disturbance, hepatotoxic rash, convulsions
Voricanazole response rates
50-90% as fungal resistance is emerging
