Cyanosis: Pathophysiology and Differential Diagnosis

By S. GILBERT BLOUNT, JR.

HE WORD C Y A N O S I S is derived from the Greek and in its strictest sense

T means dark blue. The general and basic concepts leading to our under-
standing of cyanosis were delineated many years ago. 1-3'5"7 Cyanosis to the
clinician means a bluish color of the skin or mucous membranes. It is usually,
but not always, general in distribution and most obvious on the lips, cheeks,
nose, ears, mucous membranes, and nailbeds. This bluish discoloration is pro-
duced by the color of the blood within the capillaries of the dermal papillae,
mucous membranes, and in the subpapillary venous plexus of the dermis. It is
most frequently the result of cardiovascular or pulmonary defects and depends
on the absolute amount of reduced hemoglobin present in the blood. Less
commonly cyanosis is due to abnormal pigments within the red blood cell such
as methemoglobin and sulfhemoglobin and more rarely is the result of abnormal
pigments or other substances within the plasma.
It was determined many years ago that the presence of about 5 g of reduced
hemoglobin within the capillary blood is required before cyanosis can be de-
tected. 1,z This also may be stated to represent an oxygen unsaturation of 6.7
cc/100 cc of blood inasmuch as 1 g of hemoglobin can combine with 1.34 cc
of oxygen. Thus, as frequently pointed out in the past with profound anemia,
cyanosis may not be apparent (because of an insufficient amount of reduced
hemoglobin) even though marked degrees of arterial unsaturation exist. Con-
versely, if a patient is polycythemic, cyanosis may be readily apparent due to
the increased amount of reduced hemoglobin, although the degree of arterial
unsaturation may be minimal.
Factors that may modify the visual awareness of cyanosis were pointed out
by Lundsgaard and VanSlyke and are related to the thickness of the epidermis
which can mask the color of the blood within the underlying capillary bed. ~ The
amount and type of pigment within the skin, such as normally found in different
ethnic groups or pigment present in abnormal conditions such as jaundice or
Addison's disease, also may obscure the color of the underlying capillary and
venous blood. The extent of the capillaries and venules and the presence
of dilatation or constriction of these vessels also will affect the transmission of
the color of the blood to the surface of the skin. It should be remembered that
eyanosis is only a reflection of the amount of reduced hemoglobin within the
underlying capillaries and venules and is not necessarily a reflection of the
presence of reduced hemoglobin or the degree of oxygenation of the blood
within the arterial system.
Thus cyanosis, while frequently indicating arterial unsaturation, by no means

From the Medical Center, University of Colorado, Denver, Colo.

S. GmBEaT BLOVN%JB., M.D.: Professor of Medicine and Head, Division of Cardiology,
Medical Center, University of Colorado, Denver, Colo.

PROGRESSIN CARDIOVASCULARDISEASES,VOL. XIII, No. 6 (MAY), 1971 595

596 S. GILBERT BLOUNT

always reflects such and even when it does occur in association with arterial
desaturation, it must be appreciated that it is an imperfect reflection of the
degree of hypoxia and hypoxemia. Comroe and Botelho ~evealed these l~m-
itations in a study on normal subjects who inhaled decreasing percentages of
oxygen in a gas mixture. 4 They found considerable variation from one observer
to another, but noted that in most subjects, most observers could detect cya-
nosis at 85% arterial saturation. In other subjects, although observer variation
was again present, cyanosis could be detected only below 75% saturation. Medd
eta]. in a study of patients suffering from acute or chronic respiratory disease
also noted a less than ideal correlation between cyanosis and the degree of
arterial saturation, s In contrast to Comroe and Botelho, they evaluated the
tongue and mucous membranes of the mouth and lips for the detection of
eyanosis, as well as other areas such as the conjunctivae and nailbeds. These
observers found that cyanosis was not recorded uniformly unless the arterial
saturation was 75~o or less. They concluded that the tongue was probably the
most sensitive site for the observation of central cyanosis, although even then
the presence of cyanosis did not indicate necessarily arterial oxygen desatura-
tion. Earlobes, conjunctiva, and nailbeds are in general considered to be un-
reliable predictors of the state of arterial oxygenation, and this is probably in
part due to the fact that the earlobes and nailbeds are particularly prone to
hypoperfusion in low output states.
The importance of the type of light conditions under which the patient is
examined has been emphasized by Kelman and Nunn? This point deserves
emphasis, for it was revealed that with certain fluorescent lamps, the observer
considered that cyanosis was present when in fact the arterial hemoglobin
saturation was greater than 93%, while with other light sources, clinically sig-
nificant degrees of arterial hypoxemia could be missed. The authors considered
that it was possible for the average observer to detect arterial hypoxemia at a
saturation level of about 90~. Certainly this would be contrary to the experi-
ence of this author who usually finds it impossible to feel confident about the
presence of eyanosis at a peripheral arterial saturation level of 90%. In any
event, 90~ saturation corresponds to an oxygen tension of about 58 mm Hg,
and therefore, it is obvious that a considerable decrease in arterial oxygen
tension (paO2) must exist before cyanosis becomes apparent even under ideal
lighting conditions.
Thus in general, the finding of clear-cut cyanosis usually is a reflection of the
presence of a critical amount of reduced hemoglobin within the subpapilLary
venous plexus. This reflects the presence of an abnormality of the heart or
within the lungs which leads to the passage of venous blood into the systemic
arterial circuit, bypassing the alveolar capillary membrane and resulting in
peripheral arterial desaturation. Other conditions are frequently present that
modify the degree of saturation within the capillary bed and small venous
radicles: the total hemoglobin content within the blood, the rate of blood flow
through the tissue and the state of metabolism or rate of oxygen utilization
by the tissue.
The relationship between the presence or absence of cyanosis and hypox-
emia is, therefore, a very loose one. The only way to determine the state of
CYANOSIS 597

oxygenation of the peripheral arterial blood is by the measurement of paO2.

By the measurement of the oxygen content and oxygen capacity, one then is
able to determine the percentage of hemoglobin saturation. The manometri-
cally determined carbon dioxide (CO2) content of whole blood and the meas-
urement of the pH also are required for the complete evaluation of the state
of hypoxia.
GENEBAL CONSIDERATIONSWHEN VIEWING THE 'CYANOTICPATLENT
The age of the patient is important when considering the diagnostic possi-
bilities. Clear-cut cyanosis in the newborn usually denotes a serious underlying
defect most probably cardiac in origin resulting in a shunting of venous blood
into the peripheral arterial circulation either at the level of the heart or great
vessels. However, it may indicate airway obstruction or a pulmonary or central
nervous system disorder or merely a vasomotor phenomenon. The cyanosis
due to a central right to left intracardiac shunt frequently deepens noticeably
with crying or with other forms of exertion and usually will clear incompletely
on the inhalation of 100~ oxygen while that due to a pulmonary factor will
characteristically lighten on crying and disappear on exposure to 100g oxygen.
Cyanosis in the newborn also may be the result of an abnormality within
the red blood cells and is referred to as congenital methemoglobinemia. This
is a rare disorder and presents in two groups of patients. In one type there
is an inborn deficiency of reducing enzymes within the erythrocyte. The cells
in these infants may contain as much as 40~ of the total hemoglobin in the
form of methemoglobin in contrast to the less than 0.5g methemoglobin con-
centration which is normally present. Ascorbic acid or methylene blue controls
but does not eliminate completely the methemoglobinemia. This defect in
enzyme content of the red cells is inherited as a recessive trait. More recently
a second type of congenital methemoglobinemia has been detected in which
there is an abnormal hemoglobin (hemoglobin M) which is converted to a
methemoglobin that resists reduction both by the intrinsic enzymatic reducing
agents and by ascorbic acid and methylene blue. 12"14 These cyanotic indi-
viduals are frequently asymptomatic and lead full and active lives. The defect
is inherited as a dominant trait.
Although seen rarely, a fascinating type of methemoglobinemia occurs in
infants whose milk formulas have been prepared from well water containing
nitrates or nitrites. These infants are cyanotic without having any other sig-
nificant findings or symptoms. The rather unusual condition of neonatal poly-
cythemia with transient cyanosis has been reported in infants initially having
a tentative diagnosis of cyanotic congenital heart disease. ~s This is a tempo-
rary state and the prognosis appears to be excellent although neurologic se-
quelae have been observed. Large pulmonary and cerebral arteriovenous fis-
tulas have been reported also as resulting in cyanosis in the newborn period,
although pulmonary arteriovenous fistulas usually become manifest at a later
age. ~6
Cyanosis in the older child is usually the result of a central right to left
shunt, is more obvious and the differential diagnosis less perplexing. Careful
clinical evaluation usually will disclose evidence indicating the cardiovas6ular
598 S. GILBE1RT BLOUNT

system. Historical clues to cardiovascular etiology include shortness of breath

and deepening of the eyanosis with exertion. Furthermore, evaluation of the
cardiovascular system by physical examination, the electrocardiogram and
chest film will reveal dear-cut abnormalities. However, when the cyanosis is
due to the presence of a pulmonary arteriovenous fistula or when one of the
eava returns to the left atrium, the clinical findings may be subtle.
The presence of eyanosis in this age group rarely may accompany cirrhosis
of the liver. Patients have been reported showing severe eyanosis and clubbing
and a diagnosis of cyanotic congenital heart disease is entertained seriouslyY -zl
The fact that this occurs in the younger age group and ahnost always with
the presence of an ejection systolic murmur over the pulmonary area makes
the semblance more acceptable. The presence of a normal electrocardiogram
and a normal cardiac silhouette on chest film, however, are against the diag-
nosis of cyanotic congenital heart disease. The presence of multiple small pul-
monary arteriovenous fistulae have been demonstrated in some eases of juve-
nile cirrhosis. 18,19,2~ However, in other patients, the presence of such communi-
cations has not been established.
The presence of cyanosis in older children also may be the result of diverse
types of pulmonary lesions, but much less frequently than in either the adult
patient or in the newborn.
The cause of eyanosis occurring in the adult patient is also usually apparent
upon careful clinical evaluation. The history relating the onset of the eyanosis
and an evaluation of the clinical setting within which it appears are of vital
importance in pointing toward diagnostic probabilities. Thus the relatively
sudden appearance of eyanosis suggests acute conditions such as pneumonia,
pulmonary emboli, atelectasis, pneumothorax, or pulmonary edema, while the
insidious development of eyanosis causes one to consider more chronic pul-
monary diseases. In the older patient, it is most commonly secondary to chronic
obstructive airway disease and deep eyanosis with marked dubbing is rare.
Other conditions resulting in alveolar hypoventilation should be considered in
a cyanotic adult patient and are discussed later.
In the younger adult patient, severe eyanosis with advanced clubbing is
almost always the result of congenital heart disease and specifically a right to
left intraeardiae shunt due to a defect with either obstruction to outflow from
the right ventricle or marked increase in pulmonary vascular resistance. Pul-
monary arteriovenous fistulae are more common in the adult age group and
when one encounters a cyanotic patient with little clinical evidence to sub-
stantiate chronic pulmonary disease or congenital heart disease, one should
think of the presence of a pulmonary arteriovenous fistula. A soft continuous
murmur should be carefully sought for over the entire thorax and its presence
suggests this diagnosis.
The appearance of eyanosis during adult life without evidence of under-
lying cardiovascular or pulmonary disease, particularly in the unstable patient,
should lead to a careful investigation of ingested medications. Methemoglobi-
nemia or sulfhemoglobinemia may be the cause of the eyanosis in these cir-
cumstances. 22-25 A positive history of drug ingestion in many of these patients
may be difficult to obtain. This raises the question as to the diagnosis of en-
CYANOSIS 599

terogenous cyanosis. In the past the presence of anemia with methemoglobine-

mia and sulfhemoglobinemia sometimes was considered to be the result of a
malfunctioning gastrointestinal tract with absorption of endogenously pro-
duced nitrite. This diagnosis often has been viewed with skepticism and cur-
rently some authors believe that the surreptitious ingestion of analgesic drugs
may be responsible for the condition in some patients3 6 Methemoglobinemia
was much more common a couple of decades ago when the use of acetanilid
in proprietary headache remedies was common. Today this drug is not per-
mitted in headache medications and thus the occurrence of methemoglobine-
mia is far less common. When cyanosis is clear-cut/n an adult without the
presence of clubbing and with minimal cardiorespiratory symptoms, one should
consider strongly the diagnosis of methemoglobinemia.
While cyanosis usually is generalized, definite cyanosis on occasions may be
localized to certain areas of the body. When cyanosis tends to be sharply lo-
calized, it is usually a peripheral type of cyanosis without arterial unsaturation
and due to the presence of the localized dilatation of the subpapillary venules
and an increased amount of reduced hemoglobin within a specific area. Lo-
calized cyanosis is usually the result of obstruction to blood flow into or from
a particular area. Thus, it may be noted in an extrem/ty where obstruction to
flow is the result of an arterial embolus or thrombus or the presence of intense
vasoconstriction as with Raynaud's phenomenon. Localized cyanosis, however,
also may be noted when the primary disturbance is on the venous side of the
circulation such as in acrocyanosis or in conditions where there is obstruction
to venous flow, for example, the superior vena cava. Rarely, localized cyanosis
may be noted due to the presence of an abnormal amount of reduced hemo-
globin within the arterial system. This is referred to frequently as differential
cyanosis and is observed in patients with a patent ductus arteriosus. Thus,
cyanosis of the lower extremities and occasionally the left hand in the absence
of eyanosis of the right extremity or head, suggests the presence of right or left
shunting from the pulmonary artery to the descending aorta. This so-called
"reverse" shunt reflects a marked increase in pulmonary vascular resistance
and in addition is often associated with a coarctation of the aorta in a juxtal
or preductal position. Increased blueness of the head and upper extremities as
compared to the lower extremities may be noted in the presence of a patent
ductus and transposition of the great vessels, where oxygenated blood in the
pulmonary artery flows into the descending aorta.
The differential diagnosis of cyanosis now will be considered in more detail.
Cyanosis may be considered from many viewpoints and the following classi-
fication is general, incomplete and arbitrary.

DIFFERENTIAL DIAGNOSIS OF CyANOSlS :

Central Cyanosis
Central cyanosis is the most frequent cause of clearcut c31anosis with a c .
companying polyeythemia and clubbing. In conditions giving rise to this type
of cyanosis, an abnormal amount of reduced hemoglobin is found within the
peripheral arterial system. The causative factor usually lies within the heart,
I~00 S. GILBERT BLOUNT

the great vessels of the thoracic cavity, or the lungs and is the result of a
shunting, either on an anatomic or physiologic basis, of inadequately oxy-
genated venous blood into the pulmonary veins, chambers of the left heart,
or the aorta. The cyanosis is usually obvious and diffuse, although on occasion
differential cyanosis may exist as discussed above. A frequent cause of central
cyanosis is that due to congenital anomalies of the heart that are many in
number and certainly cannot be considered separately in this discussion. The
most marked polycythemia and advanced clubbing are seen in patients with
a congenital heart disease, and it is unusual to see this degree of polycythemia
and clubbing accompanying the cyanosis of any other etiology.
The most common cause of central cyanosis is that resulting from incom-
plete oxygenation of venous blood as it courses through the pulmonary capri-
lary bed to enter the pulmonary venous system. This is most frequently the
result of diseases or conditions involving the lung that result in an abnormal
gradient between the partial pressure of oxygen in the ambient air and that
within the alveoli leading to a decrease in the partial pressure of oxygen within
the alveoli with associated desaturation of the pulmonary venous blood. The
degree of desaturation is usually mild compared to that present in patients with
cyanotic congenital heart disease and, therefore, the degree of cyanosis is
correspondingly milder as is the severity of the clubbing. Certainly the most
prevalent pulmonary disease resulting in cyanosis due to the above type of
defect is found in the adult patient with chronic obstructive airway disease,
namely emphysema and/or chronic bronchitis. The main defect lies within
the more peripheral portions of the respiratory airways.
However, obstruction occurring at any level in the respiratory tree or in the
larnyx may result in impairment of adequate oxygenation of the blood.
An abnormal decrease in the partial pressure of oxygen within the alveoli
may be secondary to causes other than obstruction within the airway system.
These conditions result in alveolar hypoventilation and may occur under cir-
cumstances where the bellows action of the chest is impaired or when the
rate or effectiveness of respiration is affected adversely. Extreme obesity, dis-
eases involving the muscles of respiration or the neuromuscular mechanism,
deformities of the chest, or other conditions can result in such a deficiency.
Also, alveolar hypoventilation may occur with infections or other diseases
involving the central nervous system and occasionally no cause has been
manifest and the entity has been termed primary alveolar hypoventriation. 2r-at
Finally, a decrease in the partial pressure of oxygen within the alveoli may
occur with a normal gradient between ambient pO2 and alveolar pO~ when
pC2 in the atmospheric air is decreased sueh as occurs on ascent to high alti-
tude.
There remains one other diverse group of pulmonary disorders that results
in deficient oxygenation of venous blood in the face of relative preservation of
ventilatory function with normal paO2 with the defect residing within the
alveolar-capillary membrane. A low diffusing capacity is present in these dis-
orders which include the Hamman-Rich syndrome, scleroderma, sarcoidosis,
berylliosis, and asbestosis. However, many other disorders will reveal what has
CYANOSIS 601

been termed "alveolar-capillary block" and yet also have defects in ventilation-
perfusion.
The arterial oxygen tension may be depressed greatly in these particular
disorders but the paCO2 may be normal or decreased. Cyanosis is frequently
present in patients with this type of pulmonary condition.
When considering cyanosis one thinks most frequently in terms of the pres-
ence of an abnormal amount of reduced hemoglobin within the capillary bed.
However, central cyanosis may occur also under circumstances not related to
the presence of reduced hemoglobin. Intense degrees of cyanosis may be noted
clinically due to the presence of abnormal pigments within the red cells:
methemoglobin and sulfhemoglobin. The peripheral arterial saturation is nor-
mal in these patients for all available hemoglobin is oxygenated fully. How-
ever, the oxygen content of the blood is reduced. These pigments have a great
capacity to produce cyanosis and this is understood readily when it is appre-
ciated that about 5 g of reduced hemoglobin per 100 cc of blood is needed for
the clinical detection of cyanosis while 1.5 g of methemoglobin and less than
0.5 g of sulfhemoglobin will have comparable effects. In methemoglobin the
iron has been oxidized from the ferrous to the ferric form and methemoglobin
is unable to transport oxygen. However, the state is a readily reversible one
without creating red cell damage. Methemoglobin may be produced by a
number of drugs and chemicals most notorious of which are acetanilid, aniline,
nitrobenzene, the nitrophenols, sulfanilamide and its congeners, and inorganic
as well as organic nitrites and nitrates. A careful history of drug ingestion or
exposure by other avenues always should be obtained in the presence of
marked eyanosis with relatively minimal symptoms. Certainly under such cir-
etmastances, spectroscopic examination of the blood is important, for the diag-
nosis will depend ozl the identification of the abnormal pigment. Methemo-
globin may be altered to hemoglobin rapidly by treatment with methylene
blue or ascorbic acid. However, sulfhemoglobin is a stable compound and
once formed remains within the red cell until its destruction.
Peripheral Cyanosis
The second large group of patients with cyanosis will be considered under
the heading of peripheral cyanosis. Patients with this form of cyanosis fre-
quently have a pallid or ashen appearance with cold extremities. This usually
denotes normal arterial saturation and the presence of a normal amount of
reduced hemoglobin within the central arterial system. The cyanosis is the
result of the presence of an abnormal amount of reduced hemoglobin within
the peripheral capillary bed and small venules, and it may be generalized or
local. Peripheral cyanosis may be present in patients who also have a varying
degree of central cyanosis, and thus intensify or make possible the detection
of cyanosis. When generalized this form of cyanosis reveals the state of the
peripheral circulation, and may be produced by a subnormal rate of blood
flow reflecting a significant decrease in cardiac output secondary to heart dis-
ease, pulmonary embolus, or other pulmonary conditions but may also be
noted in noncardiopulmonary conditions such as with chilling.
Peripheral cyanosis frequently may be local in its distribution and be caused
602 S. GILBERT BLOUNT

by local factors, mainly operating in the extremities that result in the obstruc-
tion of flow into or returning from a particular area. This may be secondary
to arterial obstruction as noted with thrombosis or embolus. Discoloration may
also be noted in the presence of peripheral vascular disease involving small
arterioles such as Raynaud's phenomenon. Under these circumstances circula-
tion is obstructed or slowed locally resulting in the presence of an increased
amount of reduced hemoglobin. Abnormalities involving the venous system
such as acrocyanosis also may result in a form of peripheral cyanosis that is
localized. This condition is associated with claminess, coldness, and a marked
bluish discoloration of the skin, especially the hands and feet. The precise
mechanism causing this circulatory disorder involving the most peripheral parts
of the body is not exactly known. More recently it is considered that the ar-
teriolar functions of the acrocyanotic patient may be normal and that the pri-
mary disturbance lies on the venous side. 1~ The arteriolar constriction that
is present has been thought to be the result of a vascular reflex derived from
the venous side of the circulation. Other conditions resulting in mechanical
obstruction to venous flow may give rise to localized cyanosis as with venous
thrombosis in the extremities or thrombosis or obstruction in other areas just
such as the superior vena cava. Under these circumstances, venous plexuses
are dilated and brought closer to the surface causing the discoloration. Con-
tributing to the cyanosis there also may be slowed circulation and an increase
in extraction of oxygen in the capillary beds of the areas involved.
.The secondary phenomena of polycythemia and clubbing are not noted in
patients with cyanosis of the peripheral type. The blood gases are also rela-
tively normal unless there is an underlying cardiopulmonary defect.
The Functional Significance of Cyanosis and Its Complications
The presence of cyanosis per se may be well tolerated by the patient pro-
ducing minimal or no cardiorespiratory symptoms and little of jconsequence
other than the untoward cosmetic effects. However, chronically depressed ar-
terial pO2 leads to certain secondary compensating mechanisms that freqnently
result in complications that affect the life of the patient. Polycythemia is
probably the most significant of these compensating mechanisms. It develops
progressively and is dependent upon the degree and possibly duration of the
arterial desaturation. The age of the patient also may be a determining factor.
Hypoxemia with accompanying cyanosis is not necessarily synonymous with
chronic tissue hypoxia. Hypoxia at the tissue level probably does occur tran-
siently but then leads to compensatory mechanisms that almost always relieve
the cellular hypoxia and a state of homeostasis is achieved. The increase in
ventilation secondary to hypoxia is initiated by stimulation of systemic arterial
chemoreceptors. It is possible that the stimulus is intracellular hypoxia sec-
ondary, tO a decrease in the content of oxygen delivered to chemoreceptor
tissue. The resulting increase in ventilation favorably affects the blood gases
and an equilibrium isxeached. The stimulus for the increase in erythropoietic
activity also would appear to be associated with decreased oxygen content at
the cellular level. Evidence suggests that this stimulus is not the direct result
of low pO2: on the bone marrow, but that it is mediated through erythro-
CYANOSIS 603

poietin which arises predominantly from renal tissue. This results in an in-
crease in red cell formation increasing the oxygen-carrying capacity of the
blood and thus ameliorates the tissue hypoxia. A generalized chronic de-
ficiency of oxygen supply to tissues probably does not occur for any protracted
period of time. It is believed that in the steady state, the tissue utilization of
oxygen equals the uptake by the lungs2* When more oxygen is required by
the tissues, they extract more from the arterial blood and the venous oxygen
content falls and the pulmonary arterial blood then absorbs more oxygen in
its passage through the lungs. This concept is sustained by the fact that the
measurement of oxygen uptake by the lungs is usually normal in patients with
cyanotic congenital heart disease and in patients with chronic lung disease. 3a,3.
Actually, in the latter the oxygen uptake may be elevated depending upon
the work of breathing, a3
A study by Bing et al. of the acid-base status of children with cyanotic con-
genital heart disease revealed normal systemic arterial pH levels indicating
the adequacy of the acid-base regulatory mechanisms. 35 However, it has been
reported that rarely in certain patients with severe cyanotic congenital heart
disease that tissue hypoxia does exist with a resulting metabolic acidosis.
Huckabee has demonstrated experimentally that anerobic tissue metabolism
assumes a significant role at paO2 levels below 35 mm HgY 7 Gootman et al.
studied four infants with severe cyanotic congenital heart disease in whom
the paO2 was less than 35 mm Hg and there was increased hydrogen ion
concentrations and uncompensated acidosis2 6
The noticeable secondary phenomena occurring in patients with severe de-
grees of central cyanosis are polycythemia and digital clubbing. The exact
mechanism leading to clubbing is not understood clearly at this time and will
not be discussed further. The polycythemia as previously mentioned is a com-
pensating mechanism leading to increased oxygen carrying capacity of the
blood and recent studies suggest that it may also moderate the ventilatory
response to hypoxia and hypoxemiaY 2 However, it should be noted that with
increasing polycythemia there is an attendant rise in the hematocrit which
adversely affects the peripheral blood flow and the delivery of oxygen to the
tissues, although the accompanying hypervolemia in turn tends to counteract
the effect of the increased hematocrit on blood flow. Some of the serious com-
plications that occur in the patient with significant central cyanosis arise from
this compensatory mechanism of polycythemia. The occurrence of hemiplegia
in the cyanotic infant or adult is related to cerebral thrombosis and the poly-
cythemia, as are thrombotic lesions that are at times found in the lungs and
kidneys. The polycythemic patient also has an increased tendency to hemor-
rhage in addition to the tendency to thrombosis. A hemorrhagic diathesis re-
suiting in uncontrolled hemorrhage in the immediate postoperative period has
occurred in many patients operated upon for tetralogy of Fallot.
~Brain abscess is not an uncommon finding in the patient with cyanotic con-
genital heart disease and probably the most satisfactory explanation as to the
etiology of brain abscess is secondary infection of a cerebral infarct due to
thrombosis. The finding of elevated serum uric acid levels and symptoms of
604 s. GILBERT BLOUNT

s e c o n d a r y g o u t are n o t rare complications in the p o l y e y t h e m i c a d u l t m a l e with

cyanotic congenital h e a r t disease.
T h e a b o v e n o t e d complications developing w i t h p o l y e y t h e m i a are of in-
terest, for it is rare t h a t the d e v e l o p m e n t of c o m p e n s a t i n g m e c h a n i s m s leads
to adverse physiologic effects. T h u s while eyanosis p e r se w o u l d a p p e a r to be
of no significant consequence, the s e c o n d a r y p h e n o m e n a o c c u r r i n g w i t h pro-
l o n g e d a n d significant hypoxemia, h o w e v e r , lead to complications t h a t sig-
nificantly contribute to the m o r b i d i t y and mortality of the patient.

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