9. Lung Infection Flashcards
Outline Lower Respiratory Tract infections
There is a large clinical iceberg of LRTIs present in the community, leading to patients with infection severe enough to be admitted to hospital being at the tip of the iceberg, and the rest being hidden
The majority of infections are trivial and do not require treatment
This is because lung infections are very common;while breathing we are constantly exposed to potential infectious agents
However despite medical advances about 5% of those admitted to hospital with pneumonia die
However, we do have a multi-layered defence mechanism of the respiratory tract against these infections:
o Mechanical - URT filtration, mucociliary clearance, cough, surfactant, epithelial barrier
o Local - BALT (Bronchiole-associated lymphoid tissue), sIgA, lysozyme, transferrin, antiproteinases, alveolar macrophages
o Systemic - polymorphonuclear leucocytes, complement, immunoglobulins
The healthy lung is also sterile from the first bronchial division
What does the term ‘clinical iceberg’ mean?
‘Clinical Iceberg’ is a term used to describe the large amount of illnesses that go unreported
For example, medical statistics are created based on information from the doctors, these statistics go on to make government policies on healthcare
Outline alveolar macrophages
An alveolar macrophage (or dust cell) is a type of macrophage found in the pulmonary alveolus, near the pneumocytes, but separated from the wall
Activity of the alveolar macrophage is relatively high, because they are located at one of the major boundaries between the body and the outside world
Alveolar macrophages are frequently seen to contain granules of exogenous material such as particulate carbon that they have picked up from respiratory surfaces
Such black granules may be especially common in smoker’s lungs or long-term city dwellers
Why do we get infections?
When an infection occurs either the infectious agent overcomes the lung defences (is virulent enough) or the defences are weakened in someway to allow the infectious agent in; this weakness may be:
o Inherited - e.g. immunodeficiency
o Acquired - e.g. through smoking
Most commonly, it is a combination of both inherited and acquired susceptibility which leads to infection
Effect of smoking: cigarettes perturb mucociliary clearance, by destroying the cilia (seen by biopsy), and changing the nature of airways to stimulate increased mucus production (causing morning cough); this also makes the mucus produced more viscous and difficult to move by any remaining cilia
Effect of viruses: also perturb mucociliary clearance by destroying cilia, stimulating the production of more,
and more watery mucus (leading to a runny nose)
The cilia therefore do not have a grip on the mucus, making it difficult to get rid of:
o In addition viruses separate the tight junctions between airway epithelium and destroy epithelial cells
Outline respiratory infection syndromes
Due to a congenital abnormality, which results in weak defences
Indications that something is wrong with lung defences:
o Incidence of virulent infections
o Recurrent infections (especially pneumonia)
o Chronic infections: if the body is unable to get rid of the infection even with the help of treatment
These are hereditary (as well as acquired through viruses, cigarette smoking) causes of reduced lung defences
Examples include Kartegener’s syndrome (dextrocardia, bronchiectasis, sinusisits), primary ciliary dyskinesia
PCD - cilia don’t beath properly so mucociliary clearance doesn’t work:
o Some men are infertile because sperm tails are cilia, so they do not move successfully to reach the ovum
o Cicila present with absent dynein arms, no energy, no movement
o Other ultrastructural abnormalities involve the microtubules, which perform disorganised beating
Diagnosis of abnormal cilia is through ‘painless’ nasal brushing:
o However Nitric oxide (NO) levels also provide an excellent screening test and is less painful for patient
Outline dynein
Dynein is a family of cytoskeletal motor proteins that move along microtubules in cells
They convert the chemical energy stored in ATP to mechanical work
Dynein transports various cellular cargos, provides forces and displacements important in mitosis, and drives the beat of eukaryotic cilia and flagella
Outline bacterial infections
Broadly speaking, bacterial pathogens of the lung fall into two groups:
o Virulent species - cause pneumonia (e.g. streptococcus pneumonia)
o Less virulent species - cause bronchitis, are equipped to chronically infect airways in which the host
defences have been compromised (e.g. unencapsulated haemophilus influenza)
Outline influenza
Haemophilus influenza is the most common cause of airway infections; about 1/4 of smokers have this bacterium chronically infecting their airways
Bacteria has hair-like projections called fimbriae which anchor the bacterium to epithelial cells to stop the bacteria being moved away by ciliary beat
In an infected bronchial mucosa, the bacterial infection stimulates more mucus production, and the bacteria bind avidly to mucus
In an episode of bronchitis, the inflammatory response and antibiotics help clear the infection from the airwyad. However bacteria are equipped with ways of avoiding elimination by the body’s defences:
o They either produce factors which impair the defences, or find ways of ‘hiding’ from the defences
Bacterial strategies to avoid clearance from the airways include:
o Exoproducts - which impair mucuciliary clearance, by slowing and disorganising ciliary beat, stimulating mucus production, affecting ion transport and damaging epithelium
o Enzymes - break down local immunoglobulins
o Exoproducts - impair neutrophil, macrophage and lymphocyte function
o Adherence is increased by epithelial damage and tight junction separation
o Avoid immune surveillance - using surface heterogeneity, biofilm formation, surrounding gel and endocytosis
Outline the 3 major cell types present in the alveolar wall (pneumocytes)
Type I pneumocytes:
- Squamous Alveolar cells that form the structure of an alveolar wall
Type II pneumocytes:
- Great Alveolar cells that secrete pulmonary surfactant to lower the surface tension of water and allows the membrane to separate, thereby increasing the capability to exchange gases; surfactant is continuously released by exocytosis; it forms an underlying aqueous protein-containing hypophase and an overlying phospholipid film composed primarily of dipalmitoyl phosphatidylcholine
Macrophages:
- That destroy foreign material (such as bacteria)
Outline pneumonia
Infection of the alveoli, which is a much more serious illness than infection of the airways
5% mortality rate from hospital admissions
Clinical features: cough, sputum, fever, dyspnoea, pleural pain, headache:
o Consolidation of lung is seen on an x-ray
Histology: alveoli filled with inflammatory cells, fibrin, cell debris and bacteria:
o The most common cause is streptococcus pneumoniae; this a virulent bacterium produces a toxin called pneumolysin which punches holes into cell membranes killing the cell, therefore when studies under EM; dead cells seen with invading bacteria between them
Outline bronchiectasis
Case history: breathing difficulties as baby, reccurent childhood chest infections, purulent sputum daily o Lung infections from childhood suggests a problem with lung defences
Diagnosis: idiopathic bronchiectasis
Bronchiectasis is dilated airways in which the structural proteins have been damaged, leading to a chronic productive cough
Management includes physiotherapy (postural physiotherapy helps get phlegm out of the lungs) and many different medications
Common complaints from bronchiectasis patients include cough and sputum, recurrent infections, breathlessness and fatigue
Bronchiectasis forms a viscous cycle of infection and inflammation; microbial infection –> inflammation –> tissue damage –> impaired lung defences –> more infection
Chronic infection also involves a protease/antiprotease balance; when phagocytes engulf bacteria they spill a little protease enzyme which is normall inside the cell to kill the bacteria; this is usually neutralised by antiproteases in te mucus:
o In chronic infection, so much protease is spilled that it overwhelms the ability of the antiproteases to neutralise it
o The proteases then digest the epithelial cells, damaging them
In a bronchiectatic airway wall, the structural protein elastin has been digested away by protease enzymes released by neutrophils as they are attracted into the airway lumen by bacteria
Treatment is used to improve lung function
Outline the causes of chronic bronchial sepsis
o Congenital - e.g. pulmonary sequestration, bronchial wall abnormalities
o Mechanical obstruction - e.g. foreign body, tumour, lymph node
o Inflammatory pneumonitis- e.g. gastric contents, caustic gas
o Fibrosis - e.g. CFA, sarcoid
o Post-infective - e.g. TB, pneumonia
o Immunological - e.g. ABPA, post-transplant
o Impaired mucociliary clearance - e.g. CF, PCD, Youngs
o Immune deficiency e.g. hypogammaglobulinaemia
Define and outline sepsis
Sepsis is a life-threatening condition that arises when the body’s response to infection causes injury to its own tissues and organs
Common signs and symptoms include fever, increased heart rate, increased breathing rate, and confusion
There also may be symptoms related to a specific infection, such as a cough with pneumonia, or painful urination with a kidney infection
In the very young, old, and people with a weakened immune system, there may be no symptoms of a specific infection and the body temperature may be low or normal, rather than high
Severe sepsis is sepsis causing poor organ function or insufficient blood flow
Insufficient blood flow may be evident by low blood pressure, high blood lactate, or low urine output
Septic shock is low blood pressure due to sepsis that does not improve after reasonable amounts of intravenous fluids are given
Sepsis is caused by an immune response triggered by an infection
Most commonly, the infection is bacterial, but it may also be from fungi, viruses, or parasites
Outline primary ciliary dyskinesia
Primary ciliary dyskinesia is rare and is thought to be an autosomal recessive condition with incomplete penetrance:
- Ultrastructural abnormalities in the cilia, causing them to be immotile, or to move in a slow disordered fashion
- Absence of one or both of the dynein arms, but abnormalities of the microtubules or radial spokes have also been reported
- The cause of the disease in these patients is uncertain, and it may be that the ultrastructural abnormality is beyond the resolution of the electron microscope; ciliary disorientation, which means that the cilia beat in different directions, has been described in such patients but, since this abnormality can occur at sites of inflammation in chronic rhinosinusitis and following viral infections its relevance is uncertain, and it may be a secondary phenomena
Cilia line the nose, paranasal sinuses, middle ear and eustachian tube, and bronchi as far as the respiratory bronchioles, and also form the tail of spermatozoa; impaired ciliary function occurs at all these sites, and diffuse bronchiectasis is usually associated with chronic sinusitis, middle ear disease, and often but not invariably, male infertility; the condition may present in the neonatal period with pneumonia or segmental collapse due to mucus impaction, or more commonly in childhood with recurrent infections
About 50% of cases have dextrocardia and asmaller percentage full situs inversus, which is thought to be due to abnormal cellular microtubules that are involved in rotation of the organs in the embryo; when primary ciliary dyskinesia causes the clinical triad of bronchiectasis, dextrocardia and chronic sinusitis the condition is known as Kartagener’s syndrome after the German paediatrician who first described it
Define incomplete penetrance
Penetrance refers to the proportion of people with a particular genetic change (such as a mutation in a specific gene) who exhibit signs and symptoms of a genetic disorder
If some people with the mutation do not develop features of the disorder, the condition is said to have reduced (or incomplete) penetrance
