Hypoxia

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• Hypoxia
• ? ?

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Concept of Hypoxia
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The basic courses of respiration
Taking
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Parameters of blood oxygen
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Arteriovenous blood oxygen difference (A-VDO2)
19ml/dl
14ml/dl
5ml/dl
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PiO2(???)
CO2 (???)
SO2 (????)
PaO2 (???)
CO2max (???)
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Oxygenhaemoglobin dissociation curve
2,3-DPG? H ?, CO2 ? Temperature?
2,3-DPG? H?, CO2? Temperature?
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Oxygen supply of tissue
blood flow
CaO2
Oxygen consumption of tissue
(CaO2- CvO2)
blood flow
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Classification Etiology Pathogenesis
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Atmosphere
Decreased PiO2
Ventilation Diffusion
Hypotonic hypoxia
External respiratory dysfunction
Binding with Haemoglobin
Transportation of gases in blood
Venous-to-arterial shunts
Taking and utilization of oxygen in tissue cells
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Hypotonic hypoxia(?????)
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Altitude m Atmosphere mmHg PiO2 mmHg PAO2 mmHg SaO2
0 760 159 105 95
1000 680 140 90 94
2000 600 125 70 92
3000 530 110 62 90
4000 460 98 50 85
5000 405 85 45 75
6000 366 74 40 70
7000 310 65 35 60
8000 270 56 30 50
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Altitude 3700 m (Tibet Lhasa Potala Palace)



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Altitude 1532 m (yellow mountain)
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Altitude 8848 m (The Himalayas )
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Characteristics of blood O2
?
PaO2 SO2
CO2maxCaO2 A-VdO2
?
N
?/ N
?
Cyanosis (??)Cyanosis is a bluish or purplish
tinge to the skin and mucous membranes.
Approximately over 5g/dL of unoxygenated
hemoglobin in the capillaries generates the dark
blue color appreciated clinically as cyanosis.
O2 diffusion in tissue
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Hemic hypoxia
Abnormality of HB
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Hemic hypoxia ?????
Hemic hypoxia refers to the altered
affinity of HB for oxygen or decrease in amount
of HB in the blood, also can be termed as
isotonic hypoxemia (???????)?
Etiology

• Anemia?????(anemic hypoxia)
• Carbon monoxide poisoning ??????(HbCO)
• Methemoglobinemia HbFe3OH?????

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Carbon monoxide poisoning
CO combines preferentially with hemoglobin to
produce COHb, displacing oxygen and reducing
systemic arterial oxygen (O2) content. CO binds
reversibly to hemoglobin with an affinity 200-
230 times that of oxygen. Consequently,
relatively minute concentrations of the gas in
the environment can result in toxic
concentrations in human blood. Possible
mechanisms of toxicity include

• Decrease in the oxygen carrying capacity of
  blood.
• Alteration of the dissociation characteristics of
  oxyhemoglobin, further decreasing oxygen delivery
  to the tissues.
• Decrease in cellular respiration by binding with
  cytochrome a3.
• Binding to myoglobin, potentially causing
  myocardial and skeletal muscle dysfunction.

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?CO?Hb?????O2?210?,?????????0.1CO?,???????????50
??HbCO?
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Concentration Symptoms
35 ppm (0.0035) Headache and dizziness within six to eight hours of constant exposure
100 ppm (0.01) Slight headache in two to three hours
200 ppm (0.02) Slight headache within two to three hours loss of judgment
400 ppm (0.04) Frontal headache within one to two hours
800 ppm (0.08) Dizziness, nausea, and convulsions within 45 min insensible within 2 hours
1,600 ppm (0.16) Headache, tachycardia, dizziness, and nausea within 20 min death in less than 2 hours
3,200 ppm (0.32) Headache, dizziness and nausea in five to ten minutes. Death within 30 minutes.
6,400 ppm (0.64) Headache and dizziness in one to two minutes. Convulsions, respiratory arrest, and death in less than 20 minutes.
12,800 ppm (1.28) Unconsciousness after 2-3 breaths. Death in less than three minutes
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Concentration Source
0.1 ppm Natural atmosphere level
0.5 to 5 ppm Average level in homes
5 to 15 ppm Near properly adjusted gas stoves in homes
100 to 200 ppm Exhaust from automobiles in the Mexico City central area
5,000 ppm Exhaust from a home wood fire
7,000 ppm Undiluted warm car exhaust without a catalytic converter
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Table . COHb Levels and Symptomatology
10 Asymptomatic or may have headaches
20 Dizzyness, nausea, and syncope
30 Visual disturbances
40 Confusion and syncope
50 Seizures and coma
60 Cardiopulmonary dysfunction and death
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Methemoglobinemia, MHb

• Definition Methemoglobinemia is a disorder
  characterized by the presence of a higher than
  normal level of methemoglobin (metHb) in the
  blood, in which the ferrous (2) form of heme is
  oxidized to the ferric form (3) thus making the
  heme moiety unable to bind oxygen.
• In addition, the remaining monomers of
  ferrous heme within a hemoglobin tetramer bind
  their oxygen more tightly causing a left shift of
  the oxygen dissociation curve and reduced oxygen
  delivery at the tissue level.

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Causes

• Hereditary/CongenitalHemoglobin M
• Cytochrome b5 reductase deficiency (NADH
  deficiency)responsible for 95 of MetHgb
  reduction,
• NADPH deficiency of the HMP shunt
• Acquired
• Multiple drugs and toxins including aniline
  dyes, benzene, chloroquine, dapsone, local
  anesthetic agents, reglan, naphthalene, nitrites
  (including NTG and NO), primaquine,
  phenazopyridine, and sulfonamides.

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Clinical presentation

• Chronic methemoglobinemia chronically elevated
  levels of MetHgb often are asymptomatic or
  present with headache, fatiguability, or slate
  blue skin complaints.
• Acquired (acute) methemoglobinemia typically
  symptomatic due to lack of compensatory
  mechanisms cyanosis, dyspnea, fatigue, lethargy,
  AMS, shock, seizures and death. Severity depends
  on percent methemoglobinemia. (1 is normal)
• 3-15 skin discoloration
• 20 cyanosis or asx
• 25-50, HA, lightheaded, weak, chest pain,
  confusion
• 50-70 delirium, seizure, lactic acidosis
• gt70 arrhythmia and death.

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Characteristics of blood O2
?
PaO2 SO2
CO2maxCaO2 A-VdO2
N
/N
N
?
/N
?
Color of skin

• AnemiaPale skin color
• HbCOClassic cherry red skin is rare (ie, "When
  you're cherry red, you're dead") pallor is
  present more often.
• HbFe3OHBluish coloring, cyanosis

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70 70 20
normal
methemoglobin concentration
Note the chocolate brown color of
methemoglobinemia. This dark hue imparts clinical
cyanosis when methemoglobin levels are at 1.5
g/dL (approximately 10-15 methemoglobin
concentration) however, a level of 5 g/dL of
deoxygenated blood is required for similar
effects. Therefore, when methemoglobin levels are
relatively low, cyanosis may be observed without
cardiopulmonary symptoms.
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Circulatory hypoxia
hypokinetic
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Circulatory hypoxia ?????
Circulatory hypoxia refers to inadequate
blood flow leads to inadequate oxygenation of the
tissues. 1.Tissue ischemiashock, heart failure
2.Tissue congestionvenous embolism
Etiology

• Systemicshock, heart failure
• Localembolism, atherosclerosis

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Characteristics of blood O2
N
N
PaO2 SO2
CO2maxCaO2 A-VdO2
N
?
N
Color of skin

• Tissue ischemia pale
• Tissue congestion cyanosis

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Histogenous hypoxia
Dysfunction of O2 utilization
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Histogenous hypoxia ?????
Histogenous hypoxia refers to the tissue
cell cannot make use of the O2 supplied to them.
Etiology

• Tissue poisoninghistotoxic hypoxia
• cyanide, arsenide, sulphide
• Vitamin insufficiencyvitamin B1, B2, PP
• Mitochondrial damageradiation, bacteria?uremia

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Characteristics of blood O2
PaO2 SO2
CO2maxCaO2 A-VdO2
N
N
N
?
N
Color of skin

• Deceptively healthy pink to red skin color

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Functional and Metabolic Changes
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Compensatory reaction ?????
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Respiratory system
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Circulatory system
(3)????? ?????????KCa?KATP????? (4)??????
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Hematologic system
1)?????
1)????? 2)????????????

• ???? ???????,???????????,???????????
• ???? ???ESF(EPO)??,??????Hb?????
• ?????????????
• ???????????

2)????????????

• ???????2,3-DPG??,
  2,3-DPG?????????
• ???HbO2????????????
• ?paO2??8kPa?,????????????????????

2,3-DPG??????
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Tissues and cells

• ??????????????,?????
• ?????
• ??????????????
• ?????

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Hypoxia inducible factor-1(HIF-1)
VEGF, EPO, glycolysis enzymes
NATURE REVIEWS Immunology volume 9 September
2009
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Hypoxia Injury ???????????
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Tissues and cells
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1)??????
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ATP??
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• ???????????????
• ??????????????????????
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2)?????
ATP????
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Na??
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?????????? ATP??
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K??
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Ca2??
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3)?????
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Central nerve system
?????????????,?????CNS???????
???CNS????????????
???????????????????ATP???????????????????Ca2???
?????????????????
??????????????(PaO2lt28mmHg)???????????CNS????
??????????????,CNS??,????
?? ? ????? ? ???????? ? ????????
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Pathophysiology of hypoxic-ischemic brain injury
in the developing brain. During the initial phase
of energy failure, glutamate mediated
excitotoxicity and Na/K ATPase failure lead to
necrotic cell death. After transient recovery of
cerebral energy metabolism, a secondary phase of
apoptotic neuronal death occurs. ROS reactive
oxygen species
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Summary of potential neuroprotective strategies
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Respiratory system

• ?????(high altitude pulmonary edema, HAPE)
• ??4000m???14d???
• ???5.717.7
• ??????,??,??,????,?????
• ???????

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• ??????,??????
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• ????????????

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PaO2lt30mmHg
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Circulatory system

• ????????????????????
• ????????????????????????,?????????????
• ??????????????????????,?????
• ??????????????,???????????????????

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Hematologic system

• ???????
• ??????
• ???????

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Oxygen Treatment

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• ???????????????????

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Oxygen Intoxication
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????? ????????????8h??????????
????? ??23????????,?????(6??????????4?????
??????)????????
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Thank You
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??????????????
HbO2
??????
??
???
????
???????PaO2(1) 100mmHg
????(2)
?? PtO2 3040mmHg(3)
??(???) 5mmHg
????(4)
(1) PaO2??,????O2?????,?????O2?????
(2) ??????,????????,?????????O2??
(3) ???????,????O2?????,????O2??????
(4) ??????,?????????O2???
??
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?????(??)
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2,3-DPG??????
???
6-?????
6-????
??????
1,6-?????
??????
3-?????
1,3-??????
DPGM
DPGP
??
2,3-DPG
3-?????
DPGP
???
2-?????
2-????????
??
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ISCHAEMIC AND HYPOXIC INJURY

• cellular response to ischaemia
• cesstion of blood flow --gt
• lack of oxygen and glucose --gt
• fall in mitochondrial ATP production --gt
• depletion of cellular ATP --gt
• failure of membrane Na/K ATPase pump
• sodium and water enter cell --gt
• swelling of endoplasmic reticulum
• failure of membrane calcium pumps --gt
• free calcium enters cytoplasm
• activates phospholipases
• membrane damage --gt
• massive entry of calcium and water into cell and
  liberation of lysosomal enzymes
• failure of protein synthesis
• mitochondrial swelling
• switch to anaerobic metabolism --gt
• fall in intracellular pH --gt activation of
  lysosomal enzymes because these have been
  liberated (see 2. failure of membrane calcium
  pumps above) --gt necrosis
• summary hypoxia causes damage because ATP is not
  produced and therefore membrane pumps cannot
  work, in particular, cytosolic free calcium is a
  potent destructive agent