Pathophysiology Flashcards
Asthma
Asthma is an inflammatory airway disease, characterised by mucous plugging, acute oedema, and bronchoconstriction. It is fully reversible
Asthma can be triggered by either extrinsic or intrinsic factors.
Extrinsic asthma is caused by exposure to an allergen that enters the body and binds to the IgE antibodies on mast cells and basophils. This causes mast cell degranulation which causes the release of inflammatory mediators including histamine, leukotrienes, cytokines, and prostaglandins. This results in increased muscous secretion and oedema. This inflammatory response causes parasympathetic stimulation resulting in bronchoconstriction.
Intrinsic asthma is caused by factors such as cold air, exercise or pollutants. The pathophysiology differs depending on the cause, though bronchoconstriction is usually due to secondary parasympathetic activation.
COPD
COPD is an encompassing term for chronic inflammatory and destructive diseases within the lung, including chronic bronchitis and emphysema. Associated bronchoconstriction is not completely reversible. Exacerbations can have infective or environmental causes and are characterised by an acute worsening of respiratory symptoms.
Emphysema – destruction of alveolar tissue and reduction in lung elasticity. The loss of recoil results in gas trapping, increasing residual lung volume. The reduced surface area for gas exchange also leads to progressively worsening hypoxaemia and hypercapnia. Auto-PEEPing is used to try prevent the alveoli from collapsing, but leads to increased pulmonary and intrathoracic pressure which can cause right-sided heart failure. pink puffers
Chronic bronchitis – bronchospasm, mucosal swelling, and increased mucus production, impairing the function of airway cilia and resulting in airway stiffening. These changes make further infections more likely and more severe. blue bloaters
Both emphysema and chronic bronchitis can result in pulmonary hypertension due to hypoxic pulmonary vasoconstriction and eventually right sided heart failure. Both are generally caused by long term exposure to irritants such as cigarette smoke or environmental or industrial pollutants.
COPD and oxygen adminsitration
In some COPD patients, excess oxygen administration can cause hypercarbia, which is why bronchodilators should be nebulised using medical air, with oxygen titrated via nasal prongs if required. Target SPO2 is 88-92%.
Mechanisms by which hypercarbia occurs are complex.
- decrease ventilatory drive
- decreased CO2 buffering capacity of haemoglobin
- absorption of CO2 from alveoli beyond obstructed airways
- the density of oxygen relative to air, increasing the work of breathing
- reversal of hypoxic pulmonary vasoconstriction, causing high levels of CO2 in poorly ventilated alveoli to diffuse back into the circulation
Croup
Croup is a viral infection of the upper airway, most common in children aged 6 months - 2 years. Usually onset of illness over a few days, a barking cough that is worse at night, and a low grade fever. It is the most common cause of stridor in children.
Epiglottitis
Epiglottitis is a bacterial infection of the upper airway, which is now relatively rare due to immunisation. Usually onset of illness over a day or two, a very sore throat, difficulty swallowing (which may cause drooling), and a high grade fever. The risk of airway occlusion is relatively high. May cause stridor.
Tracheitis
Tracheitis is a bacterial infection of the trachea, relatively uncommon and mostly affecting children. Most often due to a secondary bacterial infection following a viral infection. May cause stridor.
Cardiogenic shock
Is the inability of the heart to pump effectively, resulting in decreased cardiac output. This is usually caused by acute myocardial infarction, though may also be caused by dysrhythmia, pulmonary embolism, cardiac tamponade, myocarditis, and acute valve rupture.
The reduced cardiac output with the same preload means that blood begins to backlog. Reduced cardiac contractility and function reduced coronary artery perfusion, resulting in global ischaemia that further worsens the heart’s ability to pump, reducing cardiac output further and leading to inadequate perfusion of the entire body.
If the cardiogenic shock is secondary to left ventricular dysfunction, the backlog will be in the pulmonary circulation and often result in pulmonary oedema, and will hence usually be unresponsive to fluid administration. Rarely, the shock is due to right ventricular dysfunction, which would respond better to fluid administration.
Cardiogenic pulmonary oedema
Is the accumulation of fluid in the alveoli of the lungs, usually secondary to left ventricular dysfunction arising from ischaemia. The impaired functions of the left ventricle causes blood to backlog in the pulmonary circulation, increasing the blood hydrostatic pressure to a point that it is no longer compensated by the blood osmotic pressure. This causes a shift of fluid from the intravascular space into the interstitial space and into the lungs, impairing gas exchange and increasing respiratory effort and lung expansion occurs.
PEEP helps with CPO in 3 key ways.
- expiratory pressure splints open small and medium sized airways (recruitment)
- keeps the lungs expanded at the end of expiration, decreasing WoB and requiring less effort and pressure to open wet, stiff lungs.
- increases intrathoracic pressure, which reduces venous return to the heart and CO, reducing the pulmonary hypertension.
Leaking abdominal aortic aneurysm
An aortic dissection is a serious condition in which a tear occurs in the inner layer of the body’s main artery, the aorta. When this occurs, blood rushes through the tear, causing the inner and middle layers of the aorta to split (dissect). If the blood goes through the outside aortic wall, aortic dissection is often deadly.
- thoracic: where the aorta leaves the heart, bleeds into the thoracic cavity.
- ascending aorta: from the thoracic to below the stomach, bleeds into the thoracic cavity.
- abdominal aortic aneurysm: below the stomach, bleeds into the abdominal cavity.
This is preceded by an aneurysm, when increased pressure within the vessel causes a weak point to begin to balloon. Not all aortic aneurysms result in dissection.
Dissection
- sudden severe tearing pain; shock; collpase; chest, back, or abdominal pain; unequal pulse or BP.
Aneurysm
- usually only symptomatic if they dissect or rupture
- palpable mass and pain
Myocardial ischaemia
Myocardial ischaemia occurs when heart muscle oxygen demand exceeds supply. On an ECG, it will show as T wave inversion and/or ST segment depression. Can be due to:
- stable atherosclerosis, limiting coronary blood flow
- increased demand
- acute obstruction of coronary vessels suddenly reducing supply via vasospasm (due to, for example, sympathomimetic stimulant drugs or extreme emotional distress) or thrombus formation over unstable atherosclerosis
When ischaemia is prolonged, injury occurs. Damage is reversible at this stage. ECG shows hyperacute T waves and/or ST segment elevation.
Myocardial infarction is when tissue death occurs, and is irreversible. pathological Q waves may or may not be present on an ECG. Myocardial cells can eventually develop automaticity and spontaneously trigger own action potentials, leading to tachydysrhythmias and eventually cardiac arrest.
Acute coronary syndromes
- stable angina: atherosclerotic plaque fixed and stable, reversible hypoxia associated with exertion, relieved with rest or nitrates.
- unstable angina: unstable plaque, plaque disruptions and platelet aggregation
- NSTEMI: thrombus forms creating partial occlusion
- STEMI: thrombus develops further resulting in full occlusion
Cardiac conductivity
Chemical
- pumps, transporters, and channels move electrolytes against their concentration gradients
- required oxygen and energy to drive this process
Electrical
- uneven distribution of electrolytes creates an electrical gradient across the cell membrane
- the cell membrane is polarised with a positive and a negative side
- opening channels allow the electrolytes to move across the cell membrane and create a flow of electricity (depolarise)
Mechanical
- the electrical wave passes from one cell membrane to another, causing each to depolarise
- the depolarisation triggers the release of calcium, which causes the muscle cell to contract.
Bradydysrhythmias
Primarily due to dysfunction of the SA node, making it unable to spontaneously propagate an action potential, though can also be due to excess parasympathetic activity or AV node blocks.
Can be due to:
- SA node hypoxia
- hypothermia
- drug toxicity
- sinus bradycardia may be secondary to bowel obstruction or urinary retention
Examples include:
- atrial fibrillation: slow, narrow QRS (unless BBB present), irregular
- sinus brady/SA or AV node blocks: slow, narrow QRS (unless BBB present), regular
- idioventricular: slow, wide QRS, regular
Tachydysrhythmias
Can be due to:
- excessive sympathetic activity
- myocardial cells develop automaticity and spontaneously trigger an action potential, usually through ischaemic injury
- re-entry circuits in the heart
Examples include:
- atrial fibrillation: fast, narrow QRS (unless BBB present), irregular
- atrial flutter/SVT/sinus tachy: fast, narrow QRS (unless BBB present), regular
- VT: fast, wide QRS, regular
Shock
Shock is widespread inadequate perfusion at the cellular level. It occurs secondary to changes in either myocardial function, intravascular volume, or vascular tone.
There are 7 causes of shock.
- hypovolaemic: inadequate intravascular volume, for example severe dehydration or blood loss.
- anaphylactic: inflammatory mediators released in response to a severe allergic reaction.
- septic: inflammatory mediators released in response to a severe infection.
- neurogenic: loss of SNS outflow following spinal cord injury.
- hypoadrenal (adrenal crisis): inadequate levels of circulating cortisol. Often in patients with preexisting conditions e.g. addison’s disease.
- obstructive: clinical condition obstructing blood flow into or out of the heart, e.g. pulmonary embolism, tension pneumothorax, and cardiac tamponade.
- cardiogenic: low cardiac output as a result of a heart problem, e.g. dysrhythmia or MI.
Inadequate perfusion leads to cellular hypoxia, which in turn creates an energy deficit»_space; this leads to a switch from aerobic to anaerobic metabolism, of which lactic acid is a byproduct»_space; metabolic acidosis»_space; impaired cellular function, meaning organ function impaired also»_space; if not corrected leads to cell death»_space; intracellular lysosomes release digestive enzymes»_space; toxic substances enter circulation»_space; capillary endothelium damaged»_space; destruction, dysfunction, cell death.
There are 3 key compensatory mechanisms.
- SNS activation
Reduced baroceptor stimulation results in the release of adrenaline and noradrenaline»_space; systemic vasoconstriction, increased myocardial contractility, and increased heart rate»_space; increased CO and perfusion - Endocrine response
decreased arterial pressure stimulates secretion of antidiuretic hormone»_space; vasoconstriction and reabsorption at the kidneys»_space; increased preload»_space; increased CO and perfusion - RAAS activation
SNS stimulation and reduced renal perfusion via a cascade release angiotensin 2»_space; arteriolar constriction»_space; aldosterone released»_space; increased reabsorption of sodium and therefore water at kidneys, decreasing urine output.
Levels of shock
Compensated - the body’s compensatory mechanisms are working
- increased HR
- increased RR
- cool clammy skin
- vasoconstriction
- BP unchanged
- decreased urine output
Decompensated - body’s compensatory mechanisms are inadequate or failing
- rapid tachycardia
- BP begins to fall from combination of rapid tachycardia and failure of compensatory mechanisms
- altered LoC
- delayed CRT
Irreversible - metabolic acidosis, widespread cell death, organ failure, and blood sludging.
- unrecordable BP
- falling HR
- unconscious
- very near death
Anaphylaxis
Is a type 1 IgE mediated hypersensitivity reaction to an allergen. It is rapid onset and by definition requires the involvement of two or more body systems.
When a person is first exposed to the allergen, sensitisation occurs. The body recongises the allergen as a potential threat, and generates IgE antibodies on the mast cells (connective tissue) and basophils (blood).
During subsequent exposure to the allergen, the allergic reaction occurs as it cross-links with the antigens on the mast cells and basophils. This causes the widespread release of inflammatory mediators including histamines, leukotrienes, cytokines, and prostaglandins. This inflammatory response causes widespread vasodilation and increased permeability of blood vessels, and can manifest in other body systems as below:
- respiratory: bronchoconstriction, wheeze, tachypnoea
- cardiovascular: tachycardia, hypotension, collapse
- GI: abdominal cramps, diarrhoea, vomiting
- integumentary: urticaria, itch
