TRAVEL MEDICINELAPORAN AKHIR ELECTIVE STUDY IIIHEMOGLOBIN
CONCENTRATION AND CARDIAC FUNCTION PROFILE ON PEOPLE LIVE AT 1500 M
ABOVE SEA LEVEL
Oleh :Made Bhuwana Putra1002005181
Pembimbing :dr. I Putu Adiartha Griadhi, M Fis
FAKULTAS KEDOKTERANUNIVERSITAS UDAYANADENPASAR2013
CHAPTER IINTRODUCTION
1.1 BackgroundMore than 140 million people worldwide live more
than 2500 m above sea level. 80 million of them live in Asia. Even
in Bali, there are 90.150 people who live at approximately 1500 m
above sea level. 1, 2 Both the high altitude physiologist and the
intensivist are challenged by the human organism in a hypoxic
environment and the true research potentials presented by high
altitude, where the body is subjected to an essentially isolated
hypoxic challenge, are only just beginning to be realised. The
heart and pulmonary circulation in healthy highlanders have
distinct features in comparison with residents at sea level. people
native to high altitude (HA) environments live in an environment of
hypobaric hypoxia with low ambient partial pressure of oxygen. As a
consequence, they develop alveolar hypoxia, hypoxemia, and
polycythemia. Despite this, healthy highlanders are able to perform
physical activities similar to and often even more strenuous than
those of people living at sea level (SL). This phenomenon has been
ascribed to adaptive mechanisms that occur at sequential steps of
the oxygen transport system with the main purpose of decreasing the
total pO2 gradient from ambient hypoxic air to mixed venous blood
at the tissue level. 1,2All of these latter consequence may happens
because of the difference of the atmospheric pressure at high
altitude and sea level. Native highlanders show larger lung
capacities than do their lowland counterparts in a manner that
transcends genetic background. There are several obstacle in the
environtment-mitochondria route of oxygen-called oxygen
cascade-which makes the oxygen that we inspired will not be fully
administered to mitochondria. And this phenomenon is exagerated in
high altitude environtment which has lower atmospheric pressure
than at sea level. 3We can be assured that highlanders living at
more than 2500 m above sea level have all the physiology changes,
now what we were concerned more is whether people who lives at 1500
m have distinct feature concerning their cardiac function and
hemoglobin concentration. We can phisycally identified people
native to kintamani region in bali (1500 m above sea level) have
red colored skin and cheeks which cant be seen in people lives in
Denpasar which is at sea level. This fact strenghten our opinion
that even people who lives at 1500 m have their own distinct
feature related to the amount of their hemoglobin concentration
that contribute to their adaptation to the hypoxic environtment of
high altitude. 1.2 Problem IdentificationBased on the background
above, the author finds several problems as follow: 1.2.1 How does
the hemoglobin concentration profile of people who live at 1500 m
above the sea level?1.2.2 How does the cardiac function of people
who live at 1500 m above the sea level measured with Ecg?1.3
ObjectiveBased on problems above there are several objectives as
follows:to know the hemoglobin concentration and cardiac function
of people who lives at 1500 m above the sea level.1.4 BenefitSome
of benefits in this writting are as follows:This study will be
useful to increase the knowledge in this particular area and might
be used for further research.
CHAPTER IILITERATUR REVIEW
2.1 Oxygen Cascade transfer of oxygenAerobic organisms maintain
O2 homeostasis by responding to changes in O2 supply and demand in
both short and long time domains. The effective transfer of O2 from
the environment to mitochondria is critical for aerobic organisms.
Thus, rapid changes in O2 supply or demand, as might accompany
brief exposures to environmental hypoxia or arise from exercise,
are typically met with acute cardiorespiratory reflexes that
maintain tissue O2 homeostasis.3To know better about the
respiratory adaptative response of body towards high altitude
environtment we should know how this process of oxygen intake
occurs normally. Dry air at sea level where the barometric pressure
is 1 atmosphere (101.325kPa) contains 20.95% oxygen. Thus the
partial pressure of oxygen is an estimated (0.21 x 100kPa) = 21kPa.
When air is inspired it is humidified and thus the partial pressure
of oxygen is reduced by the water vapour content (6.3kPa). Thus the
inspired partial pressure of oxygen is an estimated (0.21 x (100kPa
6.3kPa)) = 19.8kPa.At the alveolus, the oxygen is mixed with carbon
dioxide. The ratio of the amount of carbon dioxide produced to
oxygen consumed is determined by the respiratory quotient (RQ),
which further reduce the amount of oxygen. Thus the alveolar
partial pressure of oxygen is an estimated (19.8 5/0.8) =
13.6kPa.Gas exchange occurs at the alveolar-capillary interface
with oxygen (and carbon dioxide) moving across this very thin
membrane (typically 0.5 micrometres thick) by diffusion down its
partial pressure gradient. The total area available for gas
exchange is a huge 50-100m2 as a result of the vast number of
alveoli in the normal lung (typically 300 million): the resistance
to gas diffusion between the gas and blood phases is consequently
very low. Oxygenated blood from the pulmonary circulation is mixed
with a small amount of blood in the arterial system that will have
bypassed oxygenated alveoli. This is known as venous admixture or
physiological shunt and consists of blood from the bronchial
circulation, Thebesian vessels (cardiac veins draining directly
into the cardiac cavities) and blood that has passed areas of poor
ventilation.The reference value for the partial pressure of oxygen
in arterial blood (PaO2) is 10.3kPa to 13.3kPa. Beyond childhood,
there is a progressive reduction with increasing age. At tissue
level oxygen diffuses from capillary blood and ultimately reaches
the mitochondria within the cells where cellular respiration
occurs. At this point the partial pressure of oxygen is 1 5kPa. The
mitochondrion will continue to respire aerobically until the
partial pressure of oxygen falls below the Pasteur Point. This is
thought to be 0.15-0.3kPa. Inspired air is then warmed and
saturated with water vapour in the upper airways
Figure 1 illustrates the cascading partial pressure of oxygen
through the respiratory system. The ranges for partial pressures
are shown for arterial blood and the mitochondrion. Artery on
Everest shows the average value for the partial pressure of oxygen
in the arterial blood of 4 climbers at 8,400m on their descent from
the summit of Mt. Everest. An oxygen partial pressure of < 8kPa
is accepted as the threshold for respiratory failure.4
Figure 1. Oxygen cascade on normal person2.2.2 Peripheral tissue
changes
Despite the importance of this final step in the delivery
ofoxygen to the mitochondria, relatively little is knownabout the
adaptive changes which take place in the peripheral tissues at
altitude. Capillary density in muscle is unchanged, although the
average diameter of muscle fibres appears to be reduced.2 Possible
advantage of this change would be to reduce the distance that
oxygenhas to diffuse from the capillaries to the mitochondria.
Muscle myoglobin appears to be increased at altitude improving
oxygen diffusion through muscle cells.2 This, perhaps, acting as an
oxygen reservoir during periods of profound cellular hypoxia.
2.2 Effect of high altitude exposure to normal cardiovascular
systemThe role of the cardiovascular system is simple; to drive the
delivery of oxygen to the tissues need it and carry away the
metabolic effluent. It needs to respond to the changing metabolic
needs of the tissues in such a way that oxygen delivery meets
demand. How it does this is complex, even more so at altitude,
where the reduced barometric pressure-compared with one at the sea
level- and therefore partial pressure of oxygen, cause further
stress on the body.42.2.1 CirculationThe major effects of acute
hypoxia on the heart and lung are shown in Figure 3. Hypoxia
directly affects the vascular tone of the pulmonary and systemic
resistance vessels and increases ventilation and sympathetic
activity via stimulation of the peripheral chemoreceptors.
Interactions occur between the direct effects of hypoxia on blood
vessels and the chemoreceptor-mediated responses in the systemic
and pulmonary circulation.4
Figure 2. Effect of hypoxia towards the cardio-pulmonary
system
The heart and pulmonary circulation in healthy people living at
HA exhibit important physiological and anatomic characteristics,
which resemble those that occur in chronic clinical conditions
associated with alveolar hypoxia, hypoxemia, and polycythemia.
Healthy HA natives have pulmonary hypertension (PH), right
ventricular hypertrophy (RVH) and increased amount of smooth muscle
cells (SMCs) in the distal pulmonary arterial branches. All these
findings become exaggerated when healthy highlanders lose their
capacity for adaptation and develop chronic mountain sickness
(CMS).2Several mechanisms appear to regulate local oxygen delivery
according to the needs of the tissues; for instance, the release of
ATP from red blood cells and the generation of NO by various ways
appear to regulate local oxygen delivery according to the needs of
the tissue. These mechanisms may decrease with prolonged stay at
high altitude when oxygen content of the blood increases because of
ventilatory acclimatization, an increase in hematocrit associated
with plasma volume reduction, and an increase in red blood cell
mass due to erythropoiesis.5
2.2.2 Heart
The consequences of acute hypoxia are an increase in heart rate
(both at rest and on exercise), myocardial contractility, and
cardiac output for the first few days. The higher the altitude,
then the greater the increase in heart rate. With acclimatization,
cardiac output falls at rest and on exercise in association with a
decrease in left ventricular work but an increase in right
ventricular work. On exercise however, even in acclimatised
subjects, heart rate for a given work load is greater than at sea
level except at maximal exercise where maximal heart rate is
reduced compared to sea level values.4 This may be due to
decreasing maximal oxygen (VO2max) consumption we can get at high
altitude environtment.
2.2.2.1 Myocardial Contractility and Coronary Circulation
The findings suggest that in spite of the severe hypoxaemia,
pulmonary hypertension and reduction in preload, cardiac
contractility is maintained even at a simulated altitude of
8000m.2Permanent residents at high altitude have a reduced coronary
blood flow compared to sea level residents because of the increased
oxygen of arterial content after by a process of acclimatization.
And yet there appears to be no increase in incidence of myocardial
ischaemia. One explanation is that there is a greater density of
coronary artery terminal branches in these residents compared to
sea level control.42.2.2.2 Stroke Volume
Both cardiac output and heart rate rise acutely with exposure to
hypoxia and there is no consistent change to stroke volume. Once
acclimatized a subjects cardiac output during exercise returns
towards sea level values whereas heart rate continues to be
elevated. Thus stroke volume must be reduced and this has been
confirmed in several studies.1 This is not due to a loss of
myocardial contractility but perhaps due to a reduction in plasma
volume and therefore preload or a reduction in cardiac filling time
secondary to the increased heart rate.2.2.2.3 Blood Pressure
Blood pressure changes little with acute exposure to altitude;
however there is usually an increase for the first few weeks when
lowlanders travel to altitude. This is probably due to an increase
in the sympathetic drive and vascular tone.4
2.3 Physiology development of HA natives Healthy HA natives have
pulmonary hypertension (PH), right ventricular hypertrophy (RVH)
and increased amount of smooth muscle cells (SMCs) in the distal
pulmonary arterial branches. PH with a mean value of PAP (PPA) of
_60 mm Hg was found in HA newborns, a finding similar to that
described at SL. After birth, however, the changes in PAP were very
different. In contrast to the fast decline at SL, PPA at HA
decreased slowly, and a mild or moderate degree of PH remained
until adult age. The calculated pulmonary vascular resistance (PVR)
was 5 times greater at HA than at SL. The postnatal persistence of
PH at HA implies a delayed closure of ductus arteriosus and, as a
consequence, an increased prevalence of patent ductus arteriosus at
HA. The evidence indicates that the main factor responsible for PH
in healthy highlanders is the increased amount of SMCs in the
distal pulmonary arteries and arterioles, which increases the PVR.
Vasoconstriction is a secondary factor because the administration
of oxygen decreases the PAP only by 15% to 20%. Hypervolemia,
polycythemia, and increased blood viscosity, although considered
causal factors in earlier studies,17 are now considered secondary
factors. The main role of the structural changes in the pulmonary
vasculature is confirmed by the slow decline of PAP, which becomes
normal after 2 years of residence at SL.1,2 These development
process of adaptation is what makes them differs from those who
live at sea level.
2.3.1 Ecg profile on HA nativesThe effect of chronic hypoxia due
to high altitude on the right side of the heart is of particular
interest. Complementary fluoroscopic and ambulatory continuous
electrocardiogram studies have demonstrated that an increase in the
volume of right cavities rather than a total involvement is
responsible for heart enlargement. Measured QT interval at high
altitude was prolonged in comparison with that at sea level as long
as the R-R interval was the same. It was also noted that the
corrected QT interval at high altitude both in daytime and
nighttime was significantly prolonged when compared with that
obtained at sea level, and in particular, the corrected QT interval
at night was prolonged markedly at high altitude.5 The mechanism
for the production of right ventricular hypertrophy at high
altitudes appears to be the increased pulmonary pressure that has
been found at this altitude.
2.4 Haemodynamics
2.4.1 Plasma Volume
At altitude there is generally a reduction in plasma volume as a
result of diuresis. This is likely to be caused by changes in the
feedback loops as a result of hypoxia. Hypoxic stimulation of the
carotid bodies reduces sodium reabsorption in the kidneys via
neural pathways leading to both a natriuresis and diuresis. ANP
(and BNP) is produced in the right atrium and is normally released
as a result of atrial stretch but more recently has also been shown
to be released in the presence of hypoxia. The rapid reduction in
plasma volume on exposure to high altitude results in an increase
in haemoglobin concentration. At the same time as the reduction in
plasma volume, hypoxia stimulates renal and hepatic erythropoietin
production stimulating erythropoiesis. 4 Thus, this change in
plasma volume also has correlation with the regulation of the
erithropoiesis process occuring on high altitude environtment.
2.4.2 Regulation of Hemoglobin Concentration
The EPO gene is induced by hypoxia inducible factor-1 (HIF-1).
Interestingly this nuclear factor, which is rapidly broken down in
normoxia, but accumulates in hypoxia, is responsible for inducing
multiple other genes that may well play a part in acclimatisation
and adaptation to altitude; products include lactate dehydrogenase,
nitric oxide synthase and vascular endothelial growth factor.There
is an elevation in EPO production within the first 2 hours of
hypoxia, peaking at 24-48 hours and declining to normal The EPO
gene is induced by hypoxia inducible factor-1 (HIF-1).
Interestingly this nuclear factor, which is rapidly broken down in
normoxia, but accumulates in hypoxia, is responsible for inducing
multiple other genes that may well play a part in acclimatisation
and adaptation to altitude; products include lactate dehydrogenase,
nitric oxide synthase and vascular endothelial growth factor.There
is an elevation in EPO production within the first 2 hours of
hypoxia, peaking at 24-48 hours and declining to normal. However,
the benefit of an increase in haemoglobin on the oxygen content of
the blood is offset by the fact that it increases viscosity; there
is an exponential increase when levels rise above 18g/dl. Blood
flow is inversely proportional to viscosity and at high levels the
increase in resistance of flow through the pulmonary and systemic
circulation is sufficient to reduce cardiac output. Hence although
oxygen content may be increased, oxygen delivery to the tissues may
be reduced. 1,4
Until this day most of the research are concerning adaptation of
people live at more than 2500 m above sea level. But we know that
theoritically adaptation starts at 1500 m above sea level. The
result of this study can furthermore be continued in other region
with more samples as indicated in statistic calculation. If the
result is constant then we can conclude that there are actually
some kind of adaptation even in people live at 1500 m above the
sea.
CHAPTER IIISTRUCTURAL CONCEPT 3.1 ConceptFrom the theory and
problem identification we can conclude a structural concept as
follow:
Phsyiological Acclimatization:Cardiac systemHemoglobin
People live at 1500m
Figure 3. Research sturctural concept
Condition in which the natives of high altitude live which is
hypoxic makes their physiology adapt to it by increasing several
aspect including ventilation, cardiac output and hemoglobin
concentration, this what differentiate them with people live at sea
level altitude. We suspect that people live at moderate altitude
(1500 m) have adapt compare to those who live at sea level
altitude.
CHAPTER IVRESEARCH METHOD
4.1 Place and Time of ResearchResearch will be conducted on
January 2014 at certain Banjar in Kintamani
4.2 Research DesignThis research is categorised as descriptive
study, using cross sectional design. Cross sectional design is
design that involve observation of all of a population or, in this
study, representative subset at one spesific point of time. The
diagram of this study can be seen in figure 4 below:
PopulationPeople live at 1500 mS1HemoglobinCardiac Function
Figure 4. Diagram of descriptive cross sectional research
design
4.3 Population and Sample
4.3.1 PopulationPopulation of this research is all adult live in
Kintamani which is 1500 m above sea level, where target population
in this research is all healthy adult individual who live at
certain banjar in Kintamani.
4.3.2 Amount of Sample and Sample Taking Method
4.3.2.1 Amount of sampleThe total amount of sample will be
calculated using binomunal proportions formula which suits the
cross sectional study in condition that we dont know the number of
population and no previous research been done before: n = Z2 p
(1-p)dn = amount of minimum sample requiredZ = degree of
confidencep = powerq = 1-pd = error limit
50 = 1,962 0,8 0,3 0,01n = 50
4.3.3 Sample Inclusion CriteriaThere are several criteria made
to distinguish samples we are going to use in this study as
follow:4.3.3.1 high altitude resident is healthy adult individual
in productive age (15 64) who live at Kintamani and come to a
certain banjar in that area, willing to be taken as sample and have
no any heart and anemia disease. 4.3.4 Choosing SampleSamples will
be choosed by using quota sampling method based on the list of
resident in certain banjar in Karangasem which either have
inclusion or exclusion criteria. 27 samples is needed in this
study, by using random numeric table we can get 27 samples start
from first selection on random number and next two number as the
next sample. We are doing this over again unil we got 27
samples.
4.4 Research VariableResearch variable that we are going to use
in this study is high altitude resident, hemoglobin concentration,
and cardiac function which will be descrive in tthe next
section.
4.5 Variable Operational Definition
4.5.1 high altitude resident is healthy adult individual who
live at Kintamani, come to certain banjar, willing to be taken as
sample and have no any heart and anemia disease.
4.5.3 Hemoglobin concentration is the amount of hemoglobin in
blood taken from the samples which fit in inclusion criteria using
venipuncture method with spite and EDTA tubes, and the amount of
blood taken for each sample must fully filled the 4mL EDTA tubes or
minimally 1,5 mL for accurate interpretation.
4.5.4 Cardiac function is heart rate measurement and detection
of right ventricle hyperthropy measured by the Ecg Fukuda made from
Japan by placing electrodes on the subject.
4.6 Data Collection Method4.6.1 ToolsSpesific tools that we are
going to use in this study are:1. Fukuda Ecg from Japan used to
measure the cardiac function of each samples by putting electrode
on samples.2. Spite and sampling bottle (4mL EDTA tubes) for taking
blood samples which is then delivered to Denpasar for further
analysis.
4.6.2 MethodWe will gather all of the samples which were chosen
randomly before from the list of resident at certain banjar in
Kintamani. Then we collect the data from samples using spite and
EDTA tubes for their hemoglobin which is then analysed at the
laboratorium in Sanglah, Denpasar. And their cardiac function using
ecg. 4.7 Data AnalysisAfter we succesfully gathered all data that
we need, we will do systematic and logical arrangement to the data.
The analysis method that we are going to use is argumentative
descriptive analytic method.
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