Asthma Pathophysiology by Armando Hasudungan
Here is a transcription of the narration by Armando and his accompanying drawings.
Figure 1: Human respiratory tract and asthma definitions.
In this video we are going to talk about asthma, so here I am drawing the human
respiratory tract.
Asthma is defined as a chronic inflammation disorder of the airways. Asthma can be
divided as either atopic or non-atopic. Atopic asthma is described as extrinsic
asthma, meaning it is triggered by environmental factors and this type of asthma is
the most common. Atopic asthma involves inflammation media by systemic IgE
production.
Non atopic is an intrinsic asthma and this is far less common. This refers to an
intrinsic asthma that is not caused by exposure to an environmental factor (an
allergen). Inflammaton is mediated by local IgE production. (Figure 1).
Figure 2: Cross-section and histological representation of the normal lung.
So let’s look at a cross-section through a normal lung. Here we have the mucus layer,
we have pseudostratified endothelial cells, we have the lamina propria and the
smooth muscles surrounding all of this.
If we were to look at an asthmatic bronchiole, the lumen (the inside) would be seen
to be much narrower. But before we focus on the asthmatic bronchiole, what do the
normal histological layers look like? We have a mucus layer and the pseudostratified
columnar epithelial cells. Below this we have a basement membrane, and within the
epithelial layer we can find goblet cells that are responsible for secreting mucus into
the lumen. Below the epithelium we have the lamina propria which contains the
main cells including macrophages and mast cells. Mast cells are responsible for
secreting histamine. Below the LP we have the smooth muscle. (Figure 2).
Figure 3: Asthmatic bronchiole.
If we were to compare the normal bronchiole with the asthmatic bronchiole we
would see many differences. Firstly we would see an increase in in mucus
production, so there is an increase in goblet cells. Also there is an increase in
eosinophils in the mucus and tissue. Here we have the pseudostratified columnar
epithelial cells and below it the basement membrane thickens. Within the lamina
propria we see an increase in mast cell numbers so we get an increase in histamine
release. We also get an increase in neutrophils and T helper cells. We see smooth
muscle hypertrophy which means an increase in smooth muscle size, and this is due
to an increase in constriction. (Figure 3).
Figure 4A (left) – three main characteristics of asthma, and 4B (right) – main
symptoms.
Because of all these changes there are three characteristics of asthma. These are
airflow obstruction, bronchiole hyper-responsiveness because of histamine release,
and inflammation due to the increased release of neutrophils and other immune
cells to the area. Symptoms of asthma include shortness of breath therefore, wheeze,
chest tightness and dry irritating cough. (Figures 4A and 4B).
Figure 5: Pathophysiology of asthma.
So now that we have identified some changes that occur in an asthmatic bronchiole,
let us look at the pathophysiology. Let’s look at some players in the pathophysiology.
The main one is IgE antibodies. This are important because they bind to receptors on
mast cells forming a mast cell-IgE complex. The complex will recognise antigens and
start releasing histamine. Other players include eosinophils, dendritic cells and T
helper cells. There are 2 types of T helper cells, Th1 and Th2. In the lungs Th1 are
usually found, but in asthma there is an imbalance, and Th2 cells that are not
normally found in the lungs are up-regulated in asthma. So we have more Th2 cells
in the lungs of asthmatics.
Th1 usually promotes inflammation by increasing cell-mediated immunity, but Th2
promotes inflammation by increasing the humoral immunity, promoting antibody
production, so I hope you can see how this correlates. (Figure 5).
Figure 6. Pathogenesis of atopic asthma.
By putting these cells together we can do a diagram focusing on the pathogenesis of
atopic asthma. We have the pseudostratified columnar epithelial cells and goblet
cells secreting mucus into the lumen. Below the pseudostratified columnar cells we
have the lamina propria where we have the mast cells and dendritic cells and
macrophages.
Let’s say the asthmatic inhales an allergen and this allergen will trigger a reaction.
The allergen will be engulfed by dendritic cells and then activate the dendritic cells.
The columnar epithelial cells recognise this and secrete a substance called thymicstromal lymphocyte (TSL). TSL will condition activated dendritic cells to produce
chemokines to attract specifically Th2 cells; the activated dendritic cell itself
activates the T helper cells to differentiate to Th2 and secrete chemokines to attract
Th2 to the lungs and bronchioles.
The activated T helper 2 cells do several things. Firstly the Th2 role is to promote
humoral immunity so will stimulate plasma cells thru IL13 and Il4 and this will
promote IgE production by the plasma cells.
IgE will help bind to mast cells to create the IgE-mast cell complex. Th2 itself via IL9
will stimulate or promote mast cell activity. Another important activity of Th2 cells is
to stimulate eosinophil production from the bone marrow via IL5, so you get more
eosinophils, and there is a chemotactic response occurring to attract the eosinophils
to the lungs, so we have increased eosinophil amounts in the lungs.
The inhaled allergen will bind to IgE-mast cell complex causing it to release
histamine, prostaglandins and leukotrienes. All of this will stimulate smooth muscle
in the airways to constrict, so we get bronchiole constriction. There is also a release
of stem cell factors to maintain mast cells in the area.
So if there is IgE being produced, essentially memory, whenever the same type of
allergen is inhaled again we get the whole process reoccurring. (Figure 6).
That is the end of the learning material relating to the pathogenesis of asthma.
NOTE
Asthma Pathophysiology by Armando Hasudungan
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