20-Bio-A6 Biomedical Signal Processing · May 2013
Nivaar worked solution (AI-drafted; not reviewed by a licensed engineer)
National Exams May 2013 — 04-Bio-A6, 3 hours, closed book (approved Casio/Sharp calculator only). Five questions constitute a complete exam paper; each question is of equal value; most require an essay-format answer.
Reference texts: Guyton & Hall, Textbook of Medical Physiology (13th ed.); Junqueira & Mescher, Basic Histology: Text and Atlas (14th ed.); Robbins & Cotran, Pathologic Basis of Disease (9th ed., for the Q2 autopsy case).
Question text not reproduced: the examination questions are © Engineers and Geoscientists BC. Open the official past paper (linked at the top of this page) to read the question, then follow the worked solution below.
Carbon monoxide binds the same haem iron site on haemoglobin as oxygen, but with roughly 200–250 times the affinity. It therefore competes for and occupies binding sites at partial pressures far too low to matter for a normal competitive ligand, converting haemoglobin to carboxyhaemoglobin (COHb) and directly cutting the blood's oxygen-carrying capacity. Worse, on the haem sites that still carry O$_2$, bound CO shifts the oxygen–haemoglobin dissociation curve of the remaining subunits to the left (increases their O$_2$ affinity), so even the oxygen that is carried is released to the tissues less readily. The combination — fewer sites carrying oxygen, and the ones that do releasing it poorly — is why a small inspired CO fraction, occupying only a modest percentage of the haem sites, can produce tissue hypoxia disproportionate to the amount of gas involved.
The sigmoid shape is what lets haemoglobin act as an oxygen buffer, not just a carrier. During exercise, working muscle produces heat, CO$_2$ and H$^+$, which shift the curve to the right (the Bohr effect) and lower haemoglobin's O$_2$ affinity exactly where the curve is steepest; this lets far more oxygen unload for only a modest additional fall in tissue PO$_2$, so interstitial PO$_2$ does not have to collapse to supply the extra O$_2$ demand. In conditions of low atmospheric oxygen (altitude), alveolar and arterial PO$_2$ fall onto the flat upper plateau of the curve, so arterial saturation (and hence O$_2$ content) falls much less than PO$_2$ itself — the flat top buffers arterial loading against the inspired-PO$_2$ drop; with sustained hypoxia, a rise in red-cell 2,3-DPG shifts the curve rightward, aiding tissue unloading to compensate further. In conditions of high atmospheric oxygen (hyperoxia/hyperbaric), the same plateau means haemoglobin is already essentially saturated at normal alveolar PO$_2$, so raising inspired PO$_2$ further adds very little extra carried oxygen (only a small increase in physically dissolved O$_2$); haemoglobin's saturation is buffered at its ceiling rather than rising proportionally with PO$_2$.
Normal alveolar PO$_2$ is approximately 100 mmHg (≈104 mmHg by the alveolar gas equation) and normal alveolar PCO$_2$ is approximately 40 mmHg. Alveolar PO$_2$ is raised by increased alveolar ventilation, increased inspired O$_2$ fraction (supplemental O$_2$, or altitude in the opposite direction lowering it), and is lowered by hypoventilation, high altitude (lower inspired PO$_2$), or increased O$_2$ consumption without a matching rise in ventilation. Alveolar PCO$_2$ is a direct balance between metabolic CO$_2$ production and alveolar ventilation: it rises with hypoventilation or increased CO$_2$ production (fever, exercise, sepsis) and falls with hyperventilation. Ventilation–perfusion mismatch and diffusion impairment can also alter the effective values seen by the blood without changing the "ideal" alveolar numbers themselves.
Cigarette smoke recruits neutrophils and macrophages into the lung and both stimulates their release of proteolytic enzymes (neutrophil elastase) and inactivates the natural antiprotease (alpha-1 antitrypsin) that normally restrains it, tipping the protease–antiprotease balance toward destruction of the elastin framework of alveolar walls. The result is permanent, abnormal enlargement of airspaces distal to the terminal bronchiole with destruction of their walls (centrilobular emphysema, worst in the upper lobes in smokers), loss of the elastic recoil that normally holds small airways open on expiration, and loss of alveolar surface area for gas exchange. Pathologically this produces large bullae, reduced capillary bed, and airway collapse on forced expiration (dynamic airway compression). Functionally the effects are devastating: air trapping and increased residual volume/total lung capacity, a markedly reduced FEV$_1$/FVC ratio (obstructive pattern), reduced diffusing capacity (DLCO) from the lost surface area, ventilation –perfusion mismatch, and, as the disease progresses, chronic hypoxaemia driving pulmonary vasoconstriction, pulmonary hypertension and eventual right heart failure (cor pulmonale).
