Question

explaini the basic alterations in normal perfusion that cause disease. You should include ventilation-perfusion mismatching, impaired circulation, inadequate cardiac output, and excessive perfusion demands, and clearly explain how each of these alterations deviates from normal perfusion. For each alteration, identify a minimum of two specific examples of that pathophysiologic change.

provide citations if used.

Answer 1

1. ratio (V̇/Q̇ ratio or V/Q ratio) is a ratio used to assess the efficiency and adequacy of the matching of two variables:

V̇ or V – ventilation – the air that reaches the alveoli
Q̇ or Q – perfusion – the blood that reaches the alveoli via the capillaries
The V/Q ratio can therefore be defined as the ratio of the amount of air reaching the alveoli per minute to the amount of blood reaching the alveoli per minute—a ratio of volumetric flow rates. These two variables, V & Q, constitute the main determinants of the blood oxygen (O2) and carbon dioxide (CO2) concentration.

The V/Q ratio can be measured with a ventilation/perfusion scan.A V/Q mismatch can cause a type 1 respiratory failure.Ideally, the oxygen provided via ventilation would be just enough to saturate the blood fully. In the typical adult, 1 litre of blood can hold about 200 mL of oxygen; 1 litre of dry air has about 210 mL of oxygen. Therefore, under these conditions, the ideal ventilation perfusion ratio would be about 0.95. If one were to consider humidified air (with less oxygen), then the ideal v/q ratio would be in the vicinity of 1.0, thus leading to concept of ventilation-perfusion equality or ventilation-perfusion matching. This matching may be assessed in the lung as a whole, or in individual or in sub-groups of gas-exchanging units in the lung. On the other side Ventilation-perfusion mismatch is the term used when the ventilation and the perfusion of a gas exchanging unit are not matched.

The actual values in the lung vary depending on the position within the lung. If taken as a whole, the typical value is approximately 0.8.

Because the lung is centered vertically around the heart, part of the lung is superior to the heart, and part is inferior. This has a major impact on the V/Q ratio:

apex of lung – higher

base of lung – lower

In a subject standing in orthostatic position (upright) the apex of the lung shows higher V/Q ratio, while at the base of the lung the ratio is lower but nearer to the optimal value for reaching adequate blood oxygen concentrations. While both ventilation and perfusion increase going from the apex to the base, perfusion increases to a greater degree than ventilation, lowering the V/Q ratio at the base of the lungs. The principal factor involved in the creation of this V/Q gradient between the apex and the base of the lung is gravity (this is why V/Q ratios change in positions other than the orthostatic position).

2. Ventillation :-

Gravity and the weight of the lung act on ventilation by increasing pleural pressure at the base (making it less negative) and thus reducing the alveolar volume. The lowest part of the lung in relation to gravity is called the dependent region. In the dependent region smaller alveolar volumes mean the alveoli are more compliant (more distensible) and so capable of more oxygen exchange. The apex, though showing a higher oxygen partial pressure, ventilates less efficiently since its compliance is lower and so smaller volumes are exchanged.
Perfusion :-

The impact of gravity on pulmonary perfusion expresses itself as the hydrostatic pressure of the blood passing through the branches of the pulmonary artery in order to reach the apical and basal areas of the lungs, acting synergistically with the pressure developed by the right ventricle. Thus at the apex of the lung the resulting pressure can be insufficient for developing a flow (which can be sustained only by the negative pressure generated by venous flow towards the left atrium) or even for preventing the collapse of the vascular structures surrounding the alveoli, while the base of the lung shows an intense flow due to the higher pressure.
Ventilation-PerfusionMismatch
If there is a mismatch between the alveolarventilation and the alveolar blood flow, this will be seen in the V/Q ratio. If the V/Q ratio reduces due to inadequate ventilation, gas exchange within the affected alveoli will be impaired.
Impaired Circulation :- An inadequacy of blood flow. Inadequate blood flow to a particular area of the body can result in too little oxygen being delivered to that area, a condition known as hypoxia.Peripheral vascular disease is the reduced circulation of blood to a body part, other than the brain or heart, due to a narrowed or blocked blood vessel. Risk factors include diabetes, obesity, smoking and a sedentary lifestyle.The most common symptoms of poor circulation include:
tingling.
numbness.
throbbing or stinging pain in your limbs.
pain.
muscle cramps.
Inadequate cardiac output :- Low-output symptoms, which are caused by the inability of the heart to generate enough cardiac output, leading to reducedblood flow to the brain and other vital organs. These symptoms may include lightheadedness, fatigue, and low urine output.Clinical features of the condition
Fatigue, confusion, agitation and/or decreased level of consciousness.
Cool peripheries, mottled peripheries and delayed capillary refill time.
Hypotension.
Tachycardia or bradycardia.
Thready pulse.
Raised jugular venous pressure.
Breathlessness and hypoxaemia.
Excessive Perfusion Demands :-Excessive perfusion(hyperemia) -when supply exceedsdemand-is frequently associated with formation of edema in the associated tissue. Consequently, maintaining adequate perfusion (via managing perfusion pressure and vascular patency) is vital to maintaining healthy tissue.

3. Studies on gas exchange in pulmonary embolism are not numerous. A few of them have been performed in experimental animals. The methods employed comprise the determination of gas exchange parameters, including the physiologic dead space, and the multiple inert gas elimination technique.Furthermore, not much effort has been made to relate topographical alterations of ventilation and blood flow, detected by external counting of radioactive tracers, to ventilation/ perfusion (V˚A/Q˚) disturbances responsible for impaired gas exchange in pulmonary embolism. This paper reports data on pulmonary gas exchange, V˚A/Q˚ distribution by inert gas elimination, and regional lung function by ventilation and perfusion scan in human pulmonary embolism.
4. V/Q mismatch is the most common cause of hypoxemia.Normal V/Q level is 0.8. Ventilation, perfusion and V/Q ratio are not uniform in the human lungs. There is regional heterogeneity of V/Q ratio caused by variable subatmospheric intrapleural pressure and gravity. Ventilation and perfusion is higher at the base and lower at the apex of the lungs. However, V/Q ratio is higher at the apex and lower at the base. The ratio is low at the base as the rise in perfusion is much more than the rise in ventilation. The V/Q ratio is higher at apex because the fall in perfusion is higher than the fall in ventilation at the apex. Since ventilation is responsible for gas exchange, apical region with high ratio has low alveolar CO2 content and high oxygen content and the basal region, on the other hand, has low alveolar oxygen content and high CO2 content. Only low V/Q ratio produces hypoxemia by decreasing the alveolar oxygen level (PAO2) and subsequently arterial oxygen level.There is an important compensatory mechanism due to hypoxemia, particularly when chronic. The human body will try to restrict perfusion in areas of the lungs with reduce ventilation. This is done by hypoxic pulmonary vasoconstriction (HPV) which is unique to pulmonary vasculature. By reducing perfusion to areas of the lungs with reduce ventilation, blood is diverted to the well-ventilated lung regions.The basic goal is to maintain matching between ventilation and perfusion. The pulmonary selectivity of hypoxia can be explained by the presence of an oxygen-sensitive channel in the pulmonary circulation. The vessels mainly involved in HPV are the small pulmonary arteries.Arteries with an internal diameter of 200–400 µm are most commonly involved in the animal study.HPV also possesses negative consequences when chronic. Chronic HPV causes vascular structural remodeling and subsequent development of sustained pulmonary hypertension.The inhibition of oxygen-sensitive potassium channel initiates the process of HPV. Patel et al. subsequently revealed that the K+channels involved are voltage-gated K+channels (KV), particularly KV1.5.Hypoxia inhibits the voltage-gated K+channels present in the pulmonary artery leading to accumulation of intracellular K+and depolarization of the cells. Depolarization opens up the voltage-gated L-Type Ca2+ channels resulting in Ca2+influx and vasoconstriction.