Clinical Problems in Respiratory Physiology

A 19 year old male is brought to a doctor's office in Khandallah by his mother who is very worried. He was found shortly earlier in considerable distress complaining that he was unable to breathe. He is unable to provide a coherent history.

On examination his respiratory rate is markedly increased at rest to nearly 50/min at times. There is no cough. There is no cyanosis (blue tint of lips suggesting a high level of de-oxygenated hemoglobin ) or pallor (reduction in the red colour of the conjunctival mucosa suggesting anemia). He is diaphoretic (sweaty) but afebrile. He is able to speak in short sentences but seems anxious and only answers simple questions. He is making use of accessory respiratory muscles and his breaths are deep with marked chest wall movement. On auscultation of his chest there are prominent air sounds with no adventitiae (added sounds).

* what is a normal adult resting respiratory rate (from your own experience)?

For discussion; rather variable--perhaps around 12/min

* is this asthma, or an airway problem generally?

In asthma there is airway obstruction (due to bronchospasm): this patient is moving large amounts of air as indicated by the large chest wall movement. The narrowed airways in asthma also produce abnormal, 'musical' sounds (rhonchi) on auscultation, which are not present here. There are 'prominent air sounds'—i.e. sounds of normal air movement—on chest auscultation.
Note however that bronchospasm is a possible complication of this condition, in those with 'sensitivity' of the airway surfaces. Voluntary hyperventilation is used as a test for bronchial hypersensitivity/asthma as an alternative to inhaled methacholine.
Thus this does not seem to be an 'airway' problem.

* what will be the effect of increased ventilation on the partial pressure of carbon dioxide in the arterial blood-an increased level (hypercapnia) or a decreased level (hypocapnia)?

Hypocapnia: PaC02 is reduced.

figure adapted from Goldberg, M, Green, SB, Moss, ML et al. 1973 JAMA 223:269

The diagram above is one way of laying out in a plane the three variables involved in acid-base balance in the blood (PaCO2-the partial pressure of arterial CO2, HCO3--the concentration of the bicarbonate ion, and pH, the degree of acidity or alkalinity of the blood). The pH can also be expressed as [H+], the concentration of hydrogen ions (protons). It shows that given any two of these three values the third is determined. Note that oxygen carriage is not directly related to acid-base status. This 'nomogram' is used for the interpretation of the results of arterial blood gas tests. The region labelled 'N' indicates normal acid-base values.


* If there is little change in [HC03] so far in this patient, what is the effect of the change in PaCO2 noted in the last question on the pH of the blood?

The pH will be increased.

* What is the category of acid-base disturbance exhibited by this patient?

"Acute respiratory alkalosis" For an interactive, and fun, version of this nomogram see this site at the University of Tulane Department of Anesthesia. Note that the axes are arranged somewhat differently here from those in the nomogram above.

The patient says between gasps that he has cramping in the arms and tingling and numbness.

* an increase in blood pH (alkalosis) has some general (systemic) effects on the body, particularly on the musculoskeletal and nervous systems. Can you suggest ways in which this might occur?

Alkalosis may have systemic effects by various mechanisms, including
- lowered pH of cerebrospinal fluid (CSF) causing reflex cerebral vasoconstriction and hypoxia
- decreased delivery of oxygen to tissues due to increase in oxygen binding to hemoglobin at low PO2 (the "Bohr effect")
- increased binding of calcium ions in blood to carrier proteins causing effective hypocalcemia. Calcium is largely bound to albumin in the blood and at increased pH more calcium is bound, reducing the ionised fraction and causing a relative hypocalcemia. Calcium is important for nerve and muscle function.

Calcium (Ca) is required for the proper functioning of numerous intracellular and extracellular processes, including muscle contraction, nerve conduction, hormone release and blood coagulation. In addition, the Ca ion plays a unique role in intracellular signaling and is involved in the regulation of many enzymes. The maintenance of Ca homeostasis, therefore, is critical. (Merck Manual of Therapeutics, ch. 12)
Note: One physiological function which is likely to be important in the phenomenon of 'tetany' is the requirement for calcium ions in the process of neurotransmitter release at the axon terminals of nerves.

Hypocalcemia causes the clinical syndrome of 'tetany'.

Tetany characteristically results from severe hypocalcemia. It can also result from reduction in the ionized fraction of plasma Ca without marked hypocalcemia, as occurs in severe alkalosis. Tetany is characterized by sensory symptoms consisting of paresthesias of the lips, tongue, fingers and feet; carpopedal spasm, which may be prolonged and painful; generalized muscle aching; and spasm of facial musculature. Tetany may be overt with spontaneous symptoms or latent and requiring provocative tests to elicit. Latent tetany generally occurs at less severely decreased plasma Ca concentrations: 7 to 8 mg/dL (1.75 to 2.20 mmol/L). (Merck Manual of Therapeutics, ch. 12)

It is not clear how these effects of alkalosis combine in the brain to maintain the abnormal signal to the lungs ('increased ventilatory drive').

Instructing the patient to reduce the rate and depth of breathing has no effect. A feedback loop is occuring, which is maintaining ventilation at abnormal values.

* a similar feedback loop can maintain disordered function in other systems. Can you give an example?

Singultus (hiccups)

* bearing in mind that ventilation is controlled from the caudal brainstem (medulla oblongata) rather than by the lungs themselves, can you sketch a figure indicating the course of this circuit?

'Respiratory centre' in medulla oblongata (--> phrenic nerves etc) --> diaphragm and other muscles of ventilation --> hypocapnia --> alkalosis --> hypocalcemia and other metabolic derangements --> altered cerebral function with "anxiety" ?limbic system activation --> 'respiratory centre' in medulla oblongata -->

The young doctor does not recognise the syndrome and sends him off to a hospital. However, in the ambulance the experienced paramedics resolve his respiratory distress with a simple manouvre.

* what is the manouvre?

Having the patient re-breathe his expired air from a paper bag

* how does it solve the problem?

Expired air contains more CO2 than atmospheric air. An increased level of inhaled C02 (FICO2), increases alveolar CO2 (PAC02), increases arterial CO2 (PaCO2), and reverses systemic alkalosis. Plot this correction on the nomogram above.

* can you suggest other causes of "hyperventilation" besides the syndrome described here?

Many important conditions can cause increased respiratory efforts leading to hypocapnia. These include conditions acting in the lung (pulmonary embolism-blockage of the pulmonary blood vessels; pneumonia-lobar consolidation of lung-etc), in the brain (example, salicylate poisoning), or in other systems (e.g. heart failure, severe acute blood loss).

"Hyperventilation" refers to a situation in which hypocapnia results. Do not use the word carelessly to mean only the phenomenon ("Hyperventilation Syndrome") described in this case study.

The mother quietly informs the doctor that there was a possible precipitating event involving a break-up with a girlfriend two days before.

* in what proportion of cases does the doctor ever find out what really went on?

References

John Laffey and Brian Kavanagh: Hypocapnia. N Engl J Med. 2002 Jul 4;347(1):43-53. (local copy here)

Stephen Gluck: Acid-base. Lancet 1998; 352: 474­79 (local copy here). Respiratory acid-base disorders are mentioned in the final paragraph.


(problem based on case seen by DdeC about 1985)