CHAPTER 36Gas Transport & pH in the Lung 617Traditionally, hypoxia has been divided into four types.
Numerous other classifications have been used, but the four-
type system still has considerable utility if the definitions of
the terms are kept clearly in mind. The four categories are (1)
hypoxic hypoxia, in which the PO 2 of the arterial blood is
reduced; (2) anemic hypoxia, in which the arterial PO 2 is nor-
mal but the amount of hemoglobin available to carry O 2 is
reduced; (3) stagnant or ischemic hypoxia, in which the
blood flow to a tissue is so low that adequate O 2 is not deliv-
ered to it despite a normal PO 2 and hemoglobin concentra-
tion; and (4) histotoxic hypoxia, in which the amount of O 2
delivered to a tissue is adequate but, because of the action of a
toxic agent, the tissue cells cannot make use of the O 2 sup-
plied to them. Some specific effects of hypoxia on cells and
tissues are discussed in Clinical Box 36–3.
HYPOXIC HYPOXIA
By definition, hypoxic hypoxia is a condition of reduced arte-
rial PO 2. Hypoxic hypoxia is a problem in normal individuals
at high altitudes and is a complication of pneumonia and a va-
riety of other diseases of the respiratory system.EFFECTS OF DECREASED
BAROMETRIC PRESSUREThe composition of air stays the same, but the total baromet-
ric pressure falls with increasing altitude (Figure 36–12).
Therefore, the PO 2 also falls. At 3000 m (approximately
10,000 ft) above sea level, the alveolar PO 2 is about 60 mm Hg
and there is enough hypoxic stimulation of the chemoreceptorsCLINICAL BOX 36–2
Clinical Evaluation of Acid–Base Status
In evaluating disturbances of acid–base balance, it is im-
portant to know the pH and HCO 3 – content of arterial
plasma. Reliable pH determinations can be made with a pH
meter and a glass pH electrode. Using pH and a direct mea-
surement of the PCO 2 with a CO 2 electrode, HCO 3 – concen-
tration can be calculated. The PCO 2 is 7 to 8 mm Hg higher
and the pH 0.03 to 0.04 unit lower in venous than arterial
plasma because venous blood contains the CO 2 being car-
ried from the tissues to the lungs. Therefore, the calculated
HCO 3 – concentration is about 2 mmol/L higher. However, if
this is kept in mind, free-flowing venous blood can be sub-
stituted for arterial blood in most clinical situations.
A measurement that is of some value in the differential
diagnosis of metabolic acidosis is the anion gap. This gap,
which is something of a misnomer, refers to the difference
between the concentration of cations other than Na+ and
the concentration of anions other than Cl– and HCO 3 – in
the plasma. It consists for the most part of proteins in the
anionic form, HPO 4 2–, SO 4 2–, and organic acids, and a nor-
mal value is about 12 mEq/L. It is increased when the
plasma concentration of K+, Ca2+, or Mg+ is decreased;
when the concentration of or the charge on plasma pro-
teins is increased; or when organic anions such as lactate or
foreign anions accumulate in blood. It is decreased when
cations are increased or when plasma albumin is de-
creased. The anion gap is increased in metabolic acidosis
due to ketoacidosis, lactic acidosis, and other forms of aci-
dosis in which organic anions are increased.CLINICAL BOX 36–3
Effects of Hypoxia on Cells and Selected TissuesEffects on Cells
Hypoxia causes the production of transcription factors
(hypoxia-inducible factors; HIFs). These are made up of α
and β subunits. In normally oxygenated tissues, the α sub-
units are rapidly ubiquitinated and destroyed. However, in
hypoxic cells, the α subunits dimerize with β subunits, and
the dimers activate genes that produce angiogenic factors
and erythropoietin.
Effects on the Brain
In hypoxic hypoxia and the other generalized forms of hy-
poxia, the brain is affected first. A sudden drop in the in-
spired PO 2 to less than 20 mm Hg, which occurs, for exam-
ple, when cabin pressure is suddenly lost in a plane flying
above 16,000 m, causes loss of consciousness in 10 to 20 s
and death in 4 to 5 min. Less severe hypoxia causes a variety
of mental aberrations not unlike those produced by alcohol:
impaired judgment, drowsiness, dulled pain sensibility, ex-
citement, disorientation, loss of time sense, and headache.
Other symptoms include anorexia, nausea, vomiting, tachy-
cardia, and, when the hypoxia is severe, hypertension. The
rate of ventilation is increased in proportion to the severity
of the hypoxia of the carotid chemoreceptor cells.
Respiratory Stimulation
Dyspnea is by definition difficult or labored breathing in
which the subject is conscious of shortness of breath;
hyperpnea is the general term for an increase in the rate or
depth of breathing regardless of the patient’s subjective
sensations. Tachypnea is rapid, shallow breathing. In gen-
eral, a normal individual is not conscious of respiration until
ventilation is doubled, and breathing is not uncomfortable
until ventilation is tripled or quadrupled. Whether or not a
given level of ventilation is uncomfortable also appears to
depend on a variety of other factors. Hypercapnia and, to a
lesser extent, hypoxia cause dyspnea. An additional factor
is the effort involved in moving the air in and out of the
lungs (the work of breathing).