review concepts related to anticholinergic drugs and the treatment for asthma,
bronchitis and associated pathogenesis; chronic bronchitis and related acid/base
disturbances, perfusion, blood flow between the heart and
...
review concepts related to anticholinergic drugs and the treatment for asthma,
bronchitis and associated pathogenesis; chronic bronchitis and related acid/base
disturbances, perfusion, blood flow between the heart and lungs, asthma signs and
symptoms, bronchioles, alveolar hyperinflation with asthma, polycythemia vera;
mechanism of action of anticholinergic drugs to treat asthma
Asthma is a chronic inflammatory disease characterized by sensitization to
allergens, bronchial hyperreactivity, and reversible airway obstruction. Asthma is
initiated by a type I hypersensitivity reaction primarily mediated by IgE. Airway
epithelial exposure to antigen initiates both an innate and an adaptive immune
response in sensitized individuals. Many cells and cellular elements contribute to
the persistent inflammation of the bronchial mucosa and hyperresponsiveness of
the airways, including macrophages (dendritic cells), T helper 2 (Th2)
lymphocytes, B lymphocytes, mast cells, neutrophils, eosinophils, and basophils.
There is both an immediate (early asthmatic response) and a late (delayed)
response. In young children, airway obstruction can be more severe because of the
smaller diameter of their airways.
Asthma is caused by complex interaction of genetic and environmental factors.
Asthma results in excess mucus production and accumulation hypertrophy of
bronchial smooth muscle airflow obstruction decreased alveolar ventilation.
Asthma can take two forms: extrinsic and intrinsic. The most common symptoms
of both extrinsic and intrinsic asthma are: coughing, wheezing shortness of breath
rapid breathing chest tightness
Extrinsic: The plugs of mucus and pus from this inflammatory process can block
alveolar passageways,
leading to air-trapping and hyperinflation more signs and symptoms consistent
with the diagnosis of asthma
This process is illustrated in this image which shows the airway pathology in its
entirety mast cell degranulation triggered by the excessive amounts of IGE that
have airingly formed this individual that will bind that allergen as it enters the
airway that mast cell degranulation releases chemicals that releases mucus
production and accumulation as well as chemicals that contribute to smooth muscle
constriction that smooth muscle constriction along with mucus plugs that form
result in hyperinflation of the alveoli and eventual erosion of airway tissue
Intrinsic: can be triggered by a variety of non-allergic factors, each causing a
slightly different variation on the inflammatory process.
Regardless of the underlying cause of asthma, the disease process has both a
bronchoconstriction component and an inflammation component.
Pharmacotherapy focuses on one or both of these components to provide fast relief
for acute bronchospasms, as well as long-term control to reduce the frequency of
asthma attacks.
Chronic Bronchitis:
pathogenesis of chronic bronchitis which begins with some sort of exposure to
airborne irritants which activates bronchial smooth muscle constriction, mucus
secretion, and release of inflammatory mediators (histamine, prostaglandins,
leukotrienes, interleukins) from immune cells located in the lamina propria
These airborne irritants can include air pollution or industrial chemicals & fumes.
But the most common irritant is smoke from cigarettes and other tobacco products.
Keep in mind that all of these bronchial responses are, in fact, normal responses to
occasional inhalation of airborne irritants.
Smooth muscle constriction is important to limit passage of the irritant deeper into
the respiratory tract.
Secretion of mucus and release of inflammatory chemicals are also important to
help trap and defend against a potentially harmful substance.
The transition from a normal, protective respiratory response to a detrimental
effect occurs with ….
long-term exposure to airborne irritants which promotes
• smooth muscle hypertrophy à increased bronchoconstriction
• hypertrophy and hyperplasia of goblet cells à mucus hypersecretion
• epithelial cell metaplasia à non-ciliated squamous cells
• migration of more WBCs to site à inflammation & fibrosis in bronchial wall
• thickening and rigidity of bronchial basement membrane à narrowing of
bronchial passageways
the smooth muscle constriction, bronchial wall inflammation, and mucus plugs
lead to another issue: alveolar hyperinflation.
Because of the anatomical changes in the bronchioles associated with chronic
irritation ventilation, especially exhalation, is compromised.
Pressure differences during inhalation are high enough to force air into the alveoli.
However, during exhalation the narrowing and collapse of the air passageways
causes air to be trapped in the alveoli resulting in.
• alveolar hyperinflation à expanded thorax
• hypercapnia, (CO2 retention) and, respiratory acidosis
The high concentration of CO2 creates unfavorable conditions for gas exchange, so
there is
• decreased O2 exchange à ventilation/perfusion (V/Q) mismatch
Decreased perfusion of the pulmonary capillaries with oxygenated blood results in
• chronic pulmonary hypoxia à cyanosis
Poor ventilation, leading to decreased perfusion, causes Right to Left “shunting” to
occur. This is the phenomenon where deoxygenated blood passes from the RV to
lungs to the LV without adequate perfusion (gas exchange)
Similar to other obstructive pulmonary disorders, chronic bronchitis has both a
bronchoconstriction component and an inflammation component.
Pharmacotherapy includes:
• antitussives and expectorants – can be useful to help thin the secretions for
easier expulsion and to help control coughing episodes
• bronchodilators – fast- and long-acting agents are mainstays of chronic
bronchitis treatment
• systemic corticosteroids – particularly useful during an acute flareup/exacerbation.
• antibiotics – as needed for treatment of bacterial infections; critical to
prevent any excessive immune stimulation
Prophylactic immunizations (especially the pneumococcus vaccine and annual flu
vaccines) are important to reduce likelihood of exacerbations triggered by
respiratory infections.
Clients also benefit from working with respiratory and physiotherapists to learn
relatively simple physical measures that can help optimize quality of life for clients
with chronic bronchitis.
These physical measures include:
• chest physiotherapy using postural drainage (changes in body position) and
gravity to facilitate movement of mucus from the congested lower bronchial
airways to the trachea for easier expulsion AND
• relaxation and breathing techniques, including pursed lip breathing, similar
to how you would blow a bubble, to prolong the exhalation period
An anticholinergic agent is a substance that blocks the neurotransmitter
acetylcholine in the central and the peripheral nervous system. These agents inhibit
parasympathetic nerve impulses by selectively blocking the binding of the
neurotransmitter acetylcholine to its receptor in nerve cells. The nerve fibers of the
parasympathetic system are responsible for the involuntary movement of smooth
muscles present in the gastrointestinal tract, urinary tract, lungs, and many other
parts of the body. Anticholinergics are divided into three categories in accordance
with their specific targets in the central and peripheral nervous system:
antimuscarinic agents, ganglionic blockers, and neuromuscular blockers.
Cardiovascular: GRANT FRIBERG, ERICA LUDWIG, Sheila Cardoniga
review concepts related to cardiac output, cardiac contractility, preload/afterload,
systole/diastole, heart valves (when they are open and closed; the production of S1
& S2), stenosis of the heart valves and effects; stroke volume, Cor Pulmonale,
heart failure and physiologic processes that lead to heart failure symptoms,
hypertension, calcium binding and troponin
Review concepts related to cardiac output (cardiac contractility, preload,
afterload):
cardiac output: how much blood the heart pumps through the circulatory system
in 1 minute.
cardiac contractility: determined by Ca+2 availability and its interaction with
actin-myosin. increased by sympathetic stimulation (e.g. fever, anxiety, ↑
thyroxine). decreased by low ATP levels (e.g. ischemia, hypoxia or acidosis).
preload: volume of blood received by the heart, also the pressure of the blood on
the muscle fibers in the ventricles of the heart at the end of diastole. degree of
myocardial fiber length stretch before contraction. Degree of stretch is influenced
by end-diastolic ventricular volume (EDV) which equals the amount of blood
entering ventricle during diastole. Increased by CHF and hypervolemia. Decreased
by cardiac tamponade or hypovolemia (hemorrhage, dehydration).
afterload: pressure or resistance the heart has to overcome to eject blood. amount
of tension each ventricle must develop during systole to open SL valves & eject
blood. Influenced by ventricle wall thickness (muscle strength), Increased
thickness=decreased tension. Influenced by arterial pressure (resistance to
ejection), increased pressure=increased tension. Influenced by ventricle chamber
size (blood volume capacity), increased chamber size=increased tension. Afterload
is increased by systemic hypertension, valve disease or COPD (ex. pulmonary
hypertension). Afterload is decreased by hypotension or vasodilation.
Systole:
diastole:
heart valves (when they are open and closed; the production of S1 & S2):
stroke volume: volume of blood ejected by each ventricle/systole (70 mL) and is
determined by preload, contractility, and afterload.
Cor Pulmonale: right heart failure. Inability of the RV to provide adequate
blood flow into pulmonary circulation. Caused by pulmonary disease, RV MI, RV
hypertrophy, pulmonary SLV or tricuspid valve damage, or secondary to left heart
failure. High pulmonary vascular pressure increases RV contraction force
(afterload). RV is unable to empty completely which results in increased RV
preload. RA is unable to empty completely which results in an increased RA
preload. Increased vena cava and systemic venous volume and pressure occurs.
The fluid is forced out into peripheral tissues. This causes jugular distention,
hepatosplenomegaly, peripheral edema and left heart failure.
heart failure: cardiac dysfunction caused by inability of the heart to provide
adequate cardiac output, resulting in inadequate tissue perfusion. Types of HF, left
heart failure (CHF), right heart failure (cor pulmonale), and high-output failure.
Left heart failure: inability of LV to provide adequate blood flow into
systemic circulation. Caused by systemic hypertension, LV MI, LV hypertrophy,
aortic SLV or bicuspid valve damage secondary to right heart failure. High
systemic vascular pressure increases the LV contraction force which causes
increased afterload. The LV is unable to eject normal amount of blood which
causes an increase in LV preload. The LA is unable to eject normal amount of
blood which causes an increased LA preload. This increases the blood volume and
pressure in pulmonary veins and fluid is forced out into the pulmonary tissues.
This all causes pulmonary edema, dyspnea, and right heart failure.
Right heart failure: see Cor Pulmonale
High-Output failure: inability of heart to pump sufficient amounts of blood
to meet the circulatory needs of the body, despite normal blood volume and cardiac
contractility. Caused by severe anemia, nutritional deficiencies, hyperthyroidism,
sepsis, extreme febrile state.
Cardiac output (CO): the amount of blood the heart pumps throughout the body
per minute
CO is calculated by multiplying HR (beats per minute) by stroke volume (liter of
blood per beat)
à(HR X SV=CO), Normal adult CO is approx. 5L/min
Stroke volume: the volume of blood ejected per beat during systole
The pumping action of the heart consists of contraction and relaxation. Each
ventricular contraction and the relaxation that follows makes up the cardiac cycle.
Diastole: the period of cardiac relaxation. During diastole, the blood (from the
atrium) fills the ventricles. DIASTOLE=RELAXATION
Systole: the period of ventricular contraction. The contraction of the ventricles
forces blood out of the of the ventricles and into the pulmonary system.
SYSTOLE=CONTRACTIONàThink contrACTIONàThe action in contraction is
the pushing of the blood out of the heart
4 FACTORS AFFECT CARDIAC OUTPUT:
Preload, afterload, contractility, and heart rate
Preload: the VOLUME of blood inside the ventricle and the end of diastole
(relaxation) . It is determined by the amount of venous blood returning to the
ventricle during diastole (relaxation) and the amount of blood remaining in the
ventricle after systole (contraction)
Afterload: afterload is the RESISTANCE to ejection of blood from the left
ventricle. It is the load that the heart muscle needs to move during contraction
Contractility: represents the ability of the myocardial muscle to contract. It is the
FORCE of heart contraction. It can’t be measured directly.
Heart rate: HR is controlled by the SA node in the electrical conduction system of
the heart. Many things affect HR including medications, hormones (epinephrine
and norepinephrine), and neuropsychological factors (stressors, depression).
cardiac output: how much blood the heart pumps through the circulatory system
in 1 minute.
cardiac contractility: determined by Ca+2 availability and its interaction with
actin-myosin. increased by sympathetic stimulation (e.g. fever, anxiety, ↑
thyroxine). decreased by low ATP levels (e.g. ischemia, hypoxia or acidosis).
preload: volume of blood received by the heart, also the pressure of the blood on
the muscle fibers in the ventricles of the heart at the end of diastole. degree of
myocardial fiber length stretch before contraction. Degree of stretch is influenced
by end-diastolic ventricular volume (EDV) which equals the amount of blood
entering ventricle during diastole. Increased by CHF and hypervolemia. Decreased
by cardiac tamponade or hypovolemia (hemorrhage, dehydration).
afterload: pressure or resistance the heart has to overcome to eject blood. amount
of tension each ventricle must develop during systole to open SL valves & eject
blood. Influenced by ventricle wall thickness (muscle strength), Increased
thickness=decreased tension. Influenced by arterial pressure (resistance to
ejection), increased pressure=increased tension. Influenced by ventricle chamber
size (blood volume capacity), increased chamber size=increased tension. Afterload
is increased by systemic hypertension, valve disease or COPD (ex. pulmonary
hypertension). Afterload is decreased by hypotension or vasodilation.
Systole:
diastole:
heart valves (when they are open and closed; the production of S1 & S2): the
production of S1 and S2
Unidirectional blood flow through the heart is maintained by four valves located
within the chambers of the heart: two atrioventricular (AV) valves: tricuspid &
bicuspid (mitral) two semilunar valves: pulmonary & aortic
The superior & inferior vena cava carry systemic DEOXYgenated blood to the
right atrium. The tricuspid valve opens to allow blood flow into the right ventricle.
The pulmonary semilunar valve opens to allow blood flow into the pulmonary
trunk, a large blood vessel which divides to form the left and right pulmonary
arteries that carry blood to the lungs and eventually into the alveolar capillaries
where gas exchange will occur. The pulmonary veins return the OXYgenated
blood to the left atrium. The bicuspid valve opens to allow blood flow into the left
ventricle. The aortic semilunar valve opens to allow blood flow into the aorta, a
large blood vessel that divides to form the brachiocephalic, left common carotid,
and subclavian arteries that will further branch to carry blood to the rest of the
body. The system of four valves just described, open and close in response to
myocardial contraction and pressure changes within the heart.
The cardiac cycle begins with ventricular diastole when the muscle cells in the
ventricles are relaxed, allowing for passive movement of 70% of blood from the
atria to the ventricles, driven primarily by gravitational flow.
The remaining 30% of blood is “pumped” into the ventricles during atrial systole,
the contraction of muscle cells located in the left and right atria.
This prompts closure of the AV valves to prevent backflow of blood into the atria.
The closure of the valves can be auscultated and corresponds to the first heart
sound (S1).
As pressure builds in the ventricles from the blood volume, this pushes the
semilunar valves open. Meanwhile, the muscle cells of the ventricles contract
(ventricular systole) and 55-70% of the blood is “pumped” from the ventricles into
pulmonary and systemic circulation.
This volume of blood is referred to as the cardiac ejection fraction.
As the ventricles empty, pressure drops in the ventricles, forcing closure of the
semilunar valves to prevent backflow of blood into the ventricles. The closure of
these valves can also be auscultated and corresponds to the
second heart sound (S2).
Stenosis of the heart valves and effects: In valvular stenosis, the valve orifice is
constricted and narrowed, impeding the forward flow of blood and increasing the
workload of the cardiac chamber proximal to the diseased valve. Intraventricular or
atrial pressure increases in the chamber to overcome resistance to flow through the
valve. Increased pressure causes the myocardium to work harder, causing
myocardium hypertrophy. In valvular regurgitation (also called insufficiency or
incompetence) the valve leaflets, or cusps, fail to shut completely, permitting blood
flow to continue even when the valve is supposed to be closed. During systole or
diastole some blood leaks back into the chamber proximal to the incompetent
valve, producing a murmur on auscultation. Valvular regurgitation increases the
volume of the blood the heart must pump and increases the workload of the
affected chamber. Increased volume leads to chamber dilation, and increased
workload leads to hypertrophy.
Aortic stenosis: is the most common valvular abnormality. The three common
causes are 1.) calcific degeneration related to aging (aortic sclerosis), 2.) congenital
bicuspid valve, 3.) inflammatory damage caused by rheumatic heart disease
(RHD). Untreated aortic stenosis can lead to dysrhythmias, MI, and heart failure.
The classic manifestation of aortic stenosis are angina, syncope, and heart failure
Mitral Stenosis: impairs the flow of blood from the left atrium to the left ventricle.
Mitral stenosis is the most common form of RHD. Continued increases in left atrial
volume and pressure cause chamber dilation and hypertrophy and eventually result
in pulmonary HTN. The outcomes of untreated chronic mitral stenosis are
pulmonary HTN and right ventricular failure. The risk of developing atrial
dysrhythmias (especially fibrillation) and dysrhythmia-induced thrombi is high.
Signs and symptoms such as jugular venous distention and peripheral edema, result
from pulmonary congestion and right heart failure.
stroke volume: volume of blood ejected by each ventricle/systole (70 mL) and is
determined by preload, contractility, and afterload.
Cor Pulmonale: right heart failure. Inability of the RV to provide adequate
blood flow into pulmonary circulation. Caused by pulmonary disease, RV MI, RV
hypertrophy, pulmonary SLV or tricuspid valve damage, or secondary to left heart
failure. High pulmonary vascular pressure increases RV contraction force
(afterload). RV is unable to empty completely which results in increased RV
preload. RA is unable to empty completely which results in an increased RA
preload. Increased vena cava and systemic venous volume and pressure occurs.
The fluid is forced out into peripheral tissues. This causes jugular distention,
hepatosplenomegaly, peripheral edema and left heart failure.
heart failure: cardiac dysfunction caused by inability of the heart to provide
adequate cardiac output, resulting in inadequate tissue perfusion. Types of HF, left
heart failure (CHF), right heart failure (cor pulmonale), and high-output failure.
Left heart failure: inability of LV to provide adequate blood flow into
systemic circulation. Caused by systemic hypertension, LV MI, LV hypertrophy,
aortic SLV or bicuspid valve damage secondary to right heart failure. High
systemic vascular pressure increases the LV contraction force which causes
increased afterload. The LV is unable to eject normal amount of blood which
causes an increase in LV preload. The LA is unable to eject normal amount of
blood which causes an increased LA preload. This increases the blood volume and
pressure in pulmonary veins and fluid is forced out into the pulmonary tissues.
This all causes pulmonary edema, dyspnea, and right heart failure.
Right heart failure: see Cor Pulmonale
High-Output failure: inability of heart to pump sufficient amounts of blood
to meet the circulatory needs of the body, despite normal blood volume and cardiac
contractility. Caused by severe anemia, nutritional deficiencies, hyperthyroidism,
sepsis, extreme febrile state.
Heart Failure and Physiologic processes that lead to heart failure and
symptoms, hypertension, calcium binding and troponin
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