Hypoxia Dr.Tinku Joseph

PowerPoint presentation on Hypoxia by Dr.Tinku Joseph

1. HYPOXIAHYPOXIA
DR.TINKU JOSEPHDR.TINKU JOSEPH
DM RESIDENTDM RESIDENT
DEPARTMENT OF PULMONARY MEDICINEDEPARTMENT OF PULMONARY MEDICINE
AIMS, KOCHIAIMS, KOCHI..
Email-:[email protected]:[email protected]

2. TABLE OF CONTENTSTABLE OF CONTENTS
Hypoxia & Hypoxemia.Hypoxia & Hypoxemia.
CausesCauses
MechanismMechanism
TypesTypes
Effects of hypoxia.Effects of hypoxia.

3. HypoxiaHypoxia
A lack of oxygen at the tissue level of the body A lack of oxygen at the tissue level of the body
due to a decreased partial pressure of oxygen.due to a decreased partial pressure of oxygen.
Tissue suffers from hypoxia whenever there is Tissue suffers from hypoxia whenever there is
decreased delivery of O2 or when tissue fails to decreased delivery of O2 or when tissue fails to
utilize available O2.utilize available O2.
Normally 1000 ml/minute (550 ml/min/mNormally 1000 ml/minute (550 ml/min/m
22
) of ) of
oxygen is transported from the lungs to the oxygen is transported from the lungs to the
periphery by the circulation periphery by the circulation
Only 25% of this is utilized in a resting person. Only 25% of this is utilized in a resting person.

4. Causes of HypoxiaCauses of Hypoxia
Anemic HypoxiaAnemic Hypoxia
Carbon Monoxide IntoxicationCarbon Monoxide Intoxication
Respiratory HypoxiaRespiratory Hypoxia
Hypoxia Secondary to High AltitudeHypoxia Secondary to High Altitude
Hypoxia Secondary to Right-to-Left Hypoxia Secondary to Right-to-Left
Extrapulmonary ShuntingExtrapulmonary Shunting
Circulatory HypoxiaCirculatory Hypoxia
Specific Organ HypoxiaSpecific Organ Hypoxia
Increased O2 RequirementsIncreased O2 Requirements
Improper Oxygen UtilizationImproper Oxygen Utilization

5. HYPOXAEMIAHYPOXAEMIA
Hypoxaemia is considered to be present when Hypoxaemia is considered to be present when
arterial oxyhaemoglobin saturation is less than arterial oxyhaemoglobin saturation is less than
90 %, corresponding to an arterial blood oxygen 90 %, corresponding to an arterial blood oxygen
partial pressure (PaO2) of less than 60 mmHgpartial pressure (PaO2) of less than 60 mmHg
CausesCauses
a. Alveolar hypoventilationa. Alveolar hypoventilation
b. Ventilation-Perfusion (V/Q) mismatchb. Ventilation-Perfusion (V/Q) mismatch
-Impaired diffusion-Impaired diffusion
c. Venous admixturec. Venous admixture

6. Transport of oxygenTransport of oxygen
Oxygen delivery to a particular tissue depends onOxygen delivery to a particular tissue depends on
1.1.Amount of O2 entering the lungs.Amount of O2 entering the lungs.
2.2.Adequacy of pulmonary gas exchange.Adequacy of pulmonary gas exchange.
3.3.Blood flow to the tissue.Blood flow to the tissue.
4.4.Capacity of blood to carry O2.Capacity of blood to carry O2.

7. Transport of oxygenTransport of oxygen
The amount of O2 in the blood is determined by:The amount of O2 in the blood is determined by:
1.1.Amount of dissolved O2Amount of dissolved O2
2.2.Amount of Hb in blood.Amount of Hb in blood.
3.3.Affinity of Hb for O2.Affinity of Hb for O2.

8. Transport of oxygenTransport of oxygen
Oxygen delivery to tissue takes place in three Oxygen delivery to tissue takes place in three
steps :steps :
1.1.Uptake of 02 by the blood in the lungsUptake of 02 by the blood in the lungs
Mainly favoured by O2 pressure gradient.Mainly favoured by O2 pressure gradient.
Inspired air 150mmHgInspired air 150mmHg
Alveolar air 104mmHgAlveolar air 104mmHg
Arterial blood 94mmHgArterial blood 94mmHg
Venous blood 40mmHgVenous blood 40mmHg

10. This pressure gradient favours the diffusion of This pressure gradient favours the diffusion of
O2 from the lungs into the blood.O2 from the lungs into the blood.
Diffusion of O2 from the lungs into the blood is Diffusion of O2 from the lungs into the blood is
also influenced by :also influenced by :
 a) Thickness of alvelocapillary membrane – eg: a) Thickness of alvelocapillary membrane – eg:
pulmonary fibrosis.pulmonary fibrosis.
b) Area of membrane - eg: lung collapse or b) Area of membrane - eg: lung collapse or
uneven ventilation perfusion ratio the area takes uneven ventilation perfusion ratio the area takes
part in gas exchange is less.part in gas exchange is less.
 c) Diffusion co-efficient of O2.c) Diffusion co-efficient of O2.

11. Diffusion co-efficient depends on the solubility Diffusion co-efficient depends on the solubility
and molecular weight of a gas.and molecular weight of a gas.
Compared to Co2 the solubility of O2 in H2o is Compared to Co2 the solubility of O2 in H2o is
20 times less. So diffusion rate of O2 is less than 20 times less. So diffusion rate of O2 is less than
Co2.Co2.
Diffusion co-efficient of Diffusion co-efficient of
O2 – 1.0O2 – 1.0
Co2 – 20.3Co2 – 20.3
Co – 0.81Co – 0.81

12.  Oxygen enters the bloodOxygen enters the blood
 Dissolves in plasmaDissolves in plasma
 Dissolved oxygen diffuses into RBCDissolved oxygen diffuses into RBC
 Combines with haemoglobinCombines with haemoglobin

13. When one molecule of O2 combines with Hb,the When one molecule of O2 combines with Hb,the
affinity to O2 increases. And so further affinity to O2 increases. And so further
combination with O2 is facilitated.combination with O2 is facilitated.
Because of this O-D curve is sigmoid in shape.Because of this O-D curve is sigmoid in shape.
When Hb takes up O2 the two chains alpha 1& When Hb takes up O2 the two chains alpha 1&
beta 2 move away and when O2 is given up they beta 2 move away and when O2 is given up they
move closer.move closer.
This is responsible for increase or decrease of This is responsible for increase or decrease of
affinity of Hb to O2affinity of Hb to O2

14. Blood remains for 0.8 sec in the lung capillaries.Blood remains for 0.8 sec in the lung capillaries.
Requires 0.3 sec for complete oxygenation of Requires 0.3 sec for complete oxygenation of
Hb.Hb.
Saturated to 97% due to AV admixture & Saturated to 97% due to AV admixture &
uneven ventilation perfusion ratio(physiological)uneven ventilation perfusion ratio(physiological)

15. 2) Transport of O2 in blood2) Transport of O2 in blood
Two forms Two forms : dissolved form & combined form as : dissolved form & combined form as
HbO2.HbO2.
DISSOLVED
FORM
COMBINED
FORM
TOTAL
ARTERIAL 0.30 ml/100ml19.7ml/100ml20ml
VENOUS 0.12 14.88 15.0
Difference5.0ml

16. 2) Transport of O2 in blood2) Transport of O2 in blood
Each gram of Hb carry about 1.34ml of O2.Each gram of Hb carry about 1.34ml of O2.
Arterial blood contains 20ml of O2.Arterial blood contains 20ml of O2.
Gives about 5ml to tissue.Gives about 5ml to tissue.
100ml of blood delivers about 5ml of O2 to the 100ml of blood delivers about 5ml of O2 to the
tissue.tissue.
5 L of blood flows to organs each minute5 L of blood flows to organs each minute
Total O2 delivered to tissue in one minute is Total O2 delivered to tissue in one minute is
250ml.250ml.

17. Co-efficient of O2 utilization Co-efficient of O2 utilization = (A-V)O2 * 100 = 5 * 100= (A-V)O2 * 100 = 5 * 100
 Arterial content 20 Arterial content 20
 = 25% = 25%
Only 25% O2 is utilized by tissue.Only 25% O2 is utilized by tissue.
Rest O2 acts as reserve which may be mobilized during Rest O2 acts as reserve which may be mobilized during
stressful conditions(eg: exercise)stressful conditions(eg: exercise)

18. 3)Delivery of oxygen to tissue3)Delivery of oxygen to tissue
Pressure gradient between the arterial blood and Pressure gradient between the arterial blood and
the tissue is mainly responsible for the release of the tissue is mainly responsible for the release of
O2 to the tissue.O2 to the tissue.
Arterial blood 97mmHgArterial blood 97mmHg
Interstitial fluid 40mmHgInterstitial fluid 40mmHg
Intracellular 25mmHgIntracellular 25mmHg
Other factors : 1) pao2 2) paco2 3) tempOther factors : 1) pao2 2) paco2 3) temp
4) H+ ion 5) 2-3 DPG4) H+ ion 5) 2-3 DPG

20. Hbo2 dissociation curve:Hbo2 dissociation curve:
A curve showing relationship A curve showing relationship
between po2 & % of Hb between po2 & % of Hb
saturation.saturation.
At po2 of 26mmHg Hb is 50% At po2 of 26mmHg Hb is 50%
saturated.This is called p-50.saturated.This is called p-50.
At 40mmHg,Hb is 75% At 40mmHg,Hb is 75%
saturated.saturated.
At 60mmHg,Hb is 90% At 60mmHg,Hb is 90%
saturated.saturated.
So even if the Po2 of inspired air So even if the Po2 of inspired air
falls to 60mmg,Hb saturation is falls to 60mmg,Hb saturation is
not affected muchnot affected much

21. When curve shift to the right,O2 is released.When curve shift to the right,O2 is released.
This is influenced by 1) This is influenced by 1) pao2 in tissue – gives more pao2 in tissue – gives more
pressure gradient so O2 released.pressure gradient so O2 released.
2) paco2 – shifts curve to right.2) paco2 – shifts curve to right.
3) temp – facilitates diffusion process.3) temp – facilitates diffusion process.
4) H+ ion- - shifts curve to right.The effect of pco2 & 4) H+ ion- - shifts curve to right.The effect of pco2 &
H+ ion on O-D curve is called Bohr effect.H+ ion on O-D curve is called Bohr effect.
5) 2-3 DPG – HbA has more affinity to 2-3 DPG than 5) 2-3 DPG – HbA has more affinity to 2-3 DPG than
O2.HbF has less affinity to 2-3 DPG compared to HbA.O2.HbF has less affinity to 2-3 DPG compared to HbA.

23. 2-3 DPG usually binds to beta chains.2-3 DPG usually binds to beta chains.
2-3 DPG is formed as a side reaction during 2-3 DPG is formed as a side reaction during
glycolyisis.glycolyisis.
Its production more in Its production more in
hypoxia,alkalosis,anaemia, reduced in stored hypoxia,alkalosis,anaemia, reduced in stored
blood, hyperthyroidism & fever.blood, hyperthyroidism & fever.
Hbo2 + 2-3 DPG Hb 2-3 DPG + O2Hbo2 + 2-3 DPG Hb 2-3 DPG + O2

24. Transport of carbon DioxideTransport of carbon Dioxide
Co2 is transported from tissues to lungs.Co2 is transported from tissues to lungs.
Delivery of co2 to lungs depend on :Delivery of co2 to lungs depend on :
1.1.The blood O2 contentThe blood O2 content
2.2.Number of RBC present in the blood.Number of RBC present in the blood.
3.3.Amount of reduced Hb.Amount of reduced Hb.

25. Transport of Co2 takes place in 3 steps.Transport of Co2 takes place in 3 steps.
1) uptake of Co2 by the blood1) uptake of Co2 by the blood: co2 enters the blood : co2 enters the blood
mainly because of pressure gradient.mainly because of pressure gradient.
IntracellularIntracellular – 46mmHg – 46mmHg
Interstitial fluid Interstitial fluid – 45mmHg– 45mmHg
Arterial blood Arterial blood – 40mmHg– 40mmHg
This is also facilitated by the release of O2 to the tissue.This is also facilitated by the release of O2 to the tissue.
When Co2 enters the blood it either enters into plasma When Co2 enters the blood it either enters into plasma
or directly into RBC.or directly into RBC.

26. In the plasma:In the plasma:
A) It is hydrated to H2co3 which splits up to H+ and A) It is hydrated to H2co3 which splits up to H+ and
HCO3. H+ is neutralized.HCO3. H+ is neutralized.
Co2 + H2o H2CO3 H+ + HCO3Co2 + H2o H2CO3 H+ + HCO3
B) some amount of Co2 combines with plasma proteins B) some amount of Co2 combines with plasma proteins
and forms carbamino compounds.and forms carbamino compounds.
C) Some amount dissolves in plasma.C) Some amount dissolves in plasma.
In the RBC: In the RBC:
A) It gets hydrated and takes part in chloride shift.A) It gets hydrated and takes part in chloride shift.
Carbonic acid thus formed splits up into H+ and HCO3.Carbonic acid thus formed splits up into H+ and HCO3.
H+ is accepted by HbH+ is accepted by Hb

28. HCO3 concentration increases & diffuses out into HCO3 concentration increases & diffuses out into
plasma and to maintain electro neutrality CL ion enters plasma and to maintain electro neutrality CL ion enters
RBC.RBC.
HCO3 Cl exchange is brought about by band three HCO3 Cl exchange is brought about by band three
protein present in RBC membrane.protein present in RBC membrane.
Chloride bicarbonate shift RBC gains more number of Chloride bicarbonate shift RBC gains more number of
ions. H2O moves into RBC to maintain tonicity.ions. H2O moves into RBC to maintain tonicity.
RBC volume increases. That is why hematocrit of RBC volume increases. That is why hematocrit of
venous blood is more.venous blood is more.
Also called Humberger phenomenon.Also called Humberger phenomenon.

30. B) some amount of Co2 directly combines with Hb & B) some amount of Co2 directly combines with Hb &
forms carbamino Hbforms carbamino Hb
C) small amount of Co2 combines with proteins C) small amount of Co2 combines with proteins
present in RBC directly and forms carbamino proteins.present in RBC directly and forms carbamino proteins.
D) small amount of Co2 dissolves in cytoplasm of D) small amount of Co2 dissolves in cytoplasm of
RBC.RBC.

31. 2)Transport in the blood2)Transport in the blood
Each 100ml of blood picks up about 4ml of Each 100ml of blood picks up about 4ml of
Co2.Co2.
Co2 is transported in arterial & venous blood in Co2 is transported in arterial & venous blood in
various forms.various forms.
a) Dissolved form.a) Dissolved form.
b ) Carbamino compounds.b ) Carbamino compounds.
c ) Bicarbonate.c ) Bicarbonate.

33. 3)Delivery of Co2 to the lungs3)Delivery of Co2 to the lungs
Pressure gradientPressure gradient
Venous blood – 45mmHgVenous blood – 45mmHg
 Alveoli – 40mmHgAlveoli – 40mmHg

35. Types of HypoxiaTypes of Hypoxia
1.1.Hypoxic hypoxia.Hypoxic hypoxia.
2.2.Anaemic hypoxia.Anaemic hypoxia.
3.3.Stagnant hypoxia.Stagnant hypoxia.
4.4.Histotoxic hypoxia.Histotoxic hypoxia.

36. Hypoxic hypoxemiaHypoxic hypoxemia
Decrease in arterial Po2.Decrease in arterial Po2.
Increase in Pco2 and H+ ions.Increase in Pco2 and H+ ions.
Blood oxygen is reduced.So, delivery of O2 to tissue is Blood oxygen is reduced.So, delivery of O2 to tissue is
affected.affected.
Conditions:Conditions:
A) A) Low Po2 in inspired air Low Po2 in inspired air : eg: mines,high : eg: mines,high
altitudes,closed chambers.altitudes,closed chambers.
B) B) HypoventilationHypoventilation : eg: airway obstruction,paralysis of : eg: airway obstruction,paralysis of
respiratory muscles,depression of respiratory respiratory muscles,depression of respiratory
centre,kyphoscoliosis.centre,kyphoscoliosis.

37. C) Diffusion defect: eg: pulmonary oedema, pulmonary C) Diffusion defect: eg: pulmonary oedema, pulmonary
fibrosis,lung collapse.fibrosis,lung collapse.
D) Abnormal ventilation perfusion ratio: In large A-V D) Abnormal ventilation perfusion ratio: In large A-V
shunts,atelectasis,lung collapse and cyanotic congenital shunts,atelectasis,lung collapse and cyanotic congenital
heart disease.heart disease.

38. Anaemic hypoxemiaAnaemic hypoxemia
Arterial Po2 is normal but the amount of hemoglobin Arterial Po2 is normal but the amount of hemoglobin
available to carry O2 is reduced.available to carry O2 is reduced.
Conditions:Conditions:
A) low Hb level A) low Hb level – Po2 of inspired air is normal, lungs – Po2 of inspired air is normal, lungs
normal so diffusion of O2 into blood is normal. Hence normal so diffusion of O2 into blood is normal. Hence
po2 of blood is normal.But O2 content is reduced.po2 of blood is normal.But O2 content is reduced.
When there is mild anaemia usually O2 supply to tissue When there is mild anaemia usually O2 supply to tissue
is not affected due to concomitant rise in 2-3 DPG.is not affected due to concomitant rise in 2-3 DPG.
However during exercise sufficient O2 cannot be However during exercise sufficient O2 cannot be
delivered to the tissue.delivered to the tissue.

39. B) Carbon monoxide poisoning B) Carbon monoxide poisoning – there is high affinity – there is high affinity
of Hb to O2.of Hb to O2.
Due to effect of COHb,so O2 delivery to tissue is Due to effect of COHb,so O2 delivery to tissue is
reduced.reduced.
C) Altered Hb (methaemoglobin)C) Altered Hb (methaemoglobin) – iron is in ferric – iron is in ferric
form and oxygen does not dissociate.form and oxygen does not dissociate.

40. Stagnant hypoxemiaStagnant hypoxemia
(ischemic hypoxemia)(ischemic hypoxemia)
Blood flow to tissue is so low that adequate 02 is Blood flow to tissue is so low that adequate 02 is
not delivered to it despite a normal Po2 and not delivered to it despite a normal Po2 and
hemoglobin concentration.hemoglobin concentration.
Conditions:Conditions:
A) ShockA) Shock
B) Heart failureB) Heart failure
C) Intravascular obstruction.C) Intravascular obstruction.

41. Histotoxic hypoxemiaHistotoxic hypoxemia
Amount of 02 delivered to tissue is adequate but, Amount of 02 delivered to tissue is adequate but,
because of the action of toxic agent the tissue cells because of the action of toxic agent the tissue cells
cannot make use of the 02 supplied to them.cannot make use of the 02 supplied to them.
Conditions:Conditions:
A) Cyanide poisoning A) Cyanide poisoning – cytochrome oxidase function is – cytochrome oxidase function is
paralysed. So tissue cannot utilise O2. oxygen content paralysed. So tissue cannot utilise O2. oxygen content
of the arterial blood and blood flow rate are normalof the arterial blood and blood flow rate are normal..
B) Diptheria B) Diptheria – toxins inhibit the synthesis of one of the – toxins inhibit the synthesis of one of the
cytochromes and prevent oxygen utilization.cytochromes and prevent oxygen utilization.

42. Treatment :Treatment : 1) Methylene blue or nitrates.1) Methylene blue or nitrates.
These act by forming methaemoglobin which reacts These act by forming methaemoglobin which reacts
with cyanide to form cyanometheamoglobin a non with cyanide to form cyanometheamoglobin a non
toxic compound.toxic compound.
2) Hyberbaric oxygen therapy is less useful.2) Hyberbaric oxygen therapy is less useful.

3) Diphtheria is treated with appropriate drugs3) Diphtheria is treated with appropriate drugs..

44. Symptoms of Hypoxemia and HypoxiaSymptoms of Hypoxemia and Hypoxia
Respiratory Respiratory
Tachypnoea,breathlesness,dyspnoea,cyanosisTachypnoea,breathlesness,dyspnoea,cyanosis
Cardiovascular :Cardiovascular : increased cardiac output, palpitaions, increased cardiac output, palpitaions,
tachycardia,arrhythmias,hypotension,angina,vasodilatiotachycardia,arrhythmias,hypotension,angina,vasodilatio
n,diaphoresis and shock.n,diaphoresis and shock.
CNS :CNS :Headache,impaired judgement,inappropriate Headache,impaired judgement,inappropriate
behavouir,confusion,euphoria,delirium,restlesness, behavouir,confusion,euphoria,delirium,restlesness,
papilledema,seizures.papilledema,seizures.
Neuromuscular :Neuromuscular :weakness, tremor, asterixis, weakness, tremor, asterixis,
hyperreflexia, incoordination.hyperreflexia, incoordination.
Metabolic: Metabolic: sodium and water retension,lactic acidosissodium and water retension,lactic acidosis

46. Hypoxic Injury To Cells (1)Hypoxic Injury To Cells (1)
REVERSIBLE changes:REVERSIBLE changes:
impaired aerobic respiration (mitochondria) impaired aerobic respiration (mitochondria)
decreased ATP (energy) decreased ATP (energy)
anerobic glycolysis anerobic glycolysis
glycogen depletion glycogen depletion
accumulation of lactic acid (intracellular acidosis) accumulation of lactic acid (intracellular acidosis)
with associated nuclear chromatin clumpingwith associated nuclear chromatin clumping

47. Hypoxic Injury To Cells (2)Hypoxic Injury To Cells (2)
IRREVERSIBLE changesIRREVERSIBLE changes::
vacuolization of mitochondriavacuolization of mitochondria
swelling of lysosomes swelling of lysosomes
damage to plasma membranesdamage to plasma membranes
loss of phospholipids (decreased synthesis and increased loss of phospholipids (decreased synthesis and increased
degradation). degradation).
cytoskeletal alterations (damage to cytoskeletal-membrane cytoskeletal alterations (damage to cytoskeletal-membrane
connections, effects of cell swelling, activation of proteases) connections, effects of cell swelling, activation of proteases)
effects of free radicals (toxic oxygen radicals or toxic oxygen effects of free radicals (toxic oxygen radicals or toxic oxygen
species, produced by PMN's) species, produced by PMN's)
lipid breakdown products (free fatty acids and other with a lipid breakdown products (free fatty acids and other with a
detergent effect on cell membrane)detergent effect on cell membrane)

48. Hypoxic Injury To Cells (3)Hypoxic Injury To Cells (3)
influx of Ca++ into the cell and mitochondria with inhibition influx of Ca++ into the cell and mitochondria with inhibition
of cellular enzymesof cellular enzymes
denaturation of proteins and coagulation of cells (coagulative denaturation of proteins and coagulation of cells (coagulative
necrosis)necrosis)
cell components are degraded by inflammatory processes, cell components are degraded by inflammatory processes,
with associated further enzyme leakages and release of with associated further enzyme leakages and release of
inflammatory mediatorsinflammatory mediators
final breakdown product of dead cells include free fatty acids final breakdown product of dead cells include free fatty acids
which attract Ca++ with formation of soapswhich attract Ca++ with formation of soaps

49. Effects of HypoxiaEffects of Hypoxia
Changes in the central nervous system, Changes in the central nervous system,
particularly the higher centersparticularly the higher centers
Impaired judgment, motor incoordinationImpaired judgment, motor incoordination
Fatigue, drowsiness, apathy, inattentiveness, Fatigue, drowsiness, apathy, inattentiveness,
delayed reaction time, and reduced work delayed reaction time, and reduced work
capacitycapacity
Death usually results from respiratory failure Death usually results from respiratory failure
(Brainstem hypoxia)(Brainstem hypoxia)

50. Hypoxic-ischemic Hypoxic-ischemic
encephalopathyencephalopathy
Impaired judgment, inattentiveness, motor Impaired judgment, inattentiveness, motor
incoordination, and, at times, euphoriaincoordination, and, at times, euphoria
Circulatory arrest --> consciousness is lost Circulatory arrest --> consciousness is lost
within secondswithin seconds
Circulation is restored within 3 to 5 min --> full Circulation is restored within 3 to 5 min --> full
recovery may occur (eg. Neonatal asphyxia)recovery may occur (eg. Neonatal asphyxia)
Hypoxia-ischemia lasts beyond 3 to 5 min --> Hypoxia-ischemia lasts beyond 3 to 5 min -->
some degree of permanent cerebral damagesome degree of permanent cerebral damage

51. Hypoxic-ischemic Hypoxic-ischemic
encephalopathyencephalopathy
““Delayed injuryDelayed injury”” ( may continue for days to ( may continue for days to
weeks): 6-24 hours after the initial injury, a new weeks): 6-24 hours after the initial injury, a new
phase of neuronal destruction sets in, phase of neuronal destruction sets in,
characterized by apoptosischaracterized by apoptosis

52. Pulmonary Hypertension (PH)Pulmonary Hypertension (PH)
A common companion of many congenital A common companion of many congenital
disease (CHD)disease (CHD)
Eisenmenger syndrome: right-to-left shuntsEisenmenger syndrome: right-to-left shunts
Heart-lung transplantationHeart-lung transplantation

53. ErythrocytosisErythrocytosis
Increased erythropoietin productionIncreased erythropoietin production
Phlebotomy for recurrent hyperviscosity Phlebotomy for recurrent hyperviscosity
symptomssymptoms

54. HyperviscosityHyperviscosity
Phlebotomy, when required for symptoms of Phlebotomy, when required for symptoms of
hyperviscosity not due to dehydration or iron hyperviscosity not due to dehydration or iron
deficiency, is a simple outpatient removal of 500 deficiency, is a simple outpatient removal of 500
mL of blood over 45 min with isovolumetric mL of blood over 45 min with isovolumetric
replacement with isotonic saline (5% dextrose if replacement with isotonic saline (5% dextrose if
congestive heart failure exists)congestive heart failure exists)
Iron repletion must be done graduallyIron repletion must be done gradually

55. Abnormal Abnormal HemostasisHemostasis
Increased blood volume and engorged capillariesIncreased blood volume and engorged capillaries
Abnormalities in platelet functionAbnormalities in platelet function
Abnormalities of the extrinsic and intrinsic Abnormalities of the extrinsic and intrinsic
coagulation systemcoagulation system

56. Pathogenesis of Ischemic-associated Pathogenesis of Ischemic-associated
ThrombosisThrombosis
transcription factor early growth response-1 transcription factor early growth response-1
(Egr-1) --> de novo transcription/translation of (Egr-1) --> de novo transcription/translation of
tissue facto in mononuclear phagocytes and tissue facto in mononuclear phagocytes and
smooth muscle cells --> vascular fibrin smooth muscle cells --> vascular fibrin
deposition.deposition.
Concomitant suppression of fibrinolysis by Concomitant suppression of fibrinolysis by
hypoxia-mediated upregulation of plasminogen hypoxia-mediated upregulation of plasminogen
activator inhibitor-1activator inhibitor-1

57. Hypoxia-induced PHHypoxia-induced PH
alveolar hypoxia involves most of the lung and is prolonged --> alveolar hypoxia involves most of the lung and is prolonged -->
any usefulness of acute hypoxic any usefulness of acute hypoxic pulmonary vasoconstrictionpulmonary vasoconstriction is is
offset by a rise in pulmonary arterial pressure. offset by a rise in pulmonary arterial pressure.
structural changes in small peripheral pulmonary arteries: structural changes in small peripheral pulmonary arteries:
increased wall thickness of muscular arteries, the appearance of increased wall thickness of muscular arteries, the appearance of
new muscle in normally non-muscular arteries. new muscle in normally non-muscular arteries.
Eg. COPD, populations living at high attitudeEg. COPD, populations living at high attitude
Genetic susceptabilityGenetic susceptability
HIF (Hypoxia inducible factor)-1HIF (Hypoxia inducible factor)-1
Endothelin-1Endothelin-1
Angiotensin IIAngiotensin II

58. Oxidant tissue injury in hypoxic PHOxidant tissue injury in hypoxic PH
Increase of radical production induced by lung tissue Increase of radical production induced by lung tissue
hypoxiahypoxia
Hypoxia Hypoxia  alveolar macrophages alveolar macrophages  hydrogen hydrogen
peroxideperoxide
Nitric oxide; serum concentration of nitrotyrosine Nitric oxide; serum concentration of nitrotyrosine
(radical product of nitric oxide and superoxide (radical product of nitric oxide and superoxide
interaction)interaction)
Radicals Radicals  metabolism of vascular wall matrix proteins metabolism of vascular wall matrix proteins
 vascular remodeling vascular remodeling  Thickened and less Thickened and less
compliant peripheral pulmonary vasculaturecompliant peripheral pulmonary vasculature

59. Chronic-intermittent hypoxia Chronic-intermittent hypoxia
induced hypertensioninduced hypertension
chronic-intermittent hypoxia (as obstructive chronic-intermittent hypoxia (as obstructive
sleep apnea syndrome --> activation of the sleep apnea syndrome --> activation of the
sympathetic nervous system (included cortical sympathetic nervous system (included cortical
and brainstem components) --> hypertensionand brainstem components) --> hypertension

60. Other organs under hypoxic Other organs under hypoxic
environment environment
More acute hypoxic damages than chronic More acute hypoxic damages than chronic
damagesdamages
KidneyKidney
LiverLiver
IntestineIntestine
PancreasPancreas

61. ReferenceReference
HarrisonHarrison’’s Principles of Internal Medicine, 15th ed.s Principles of Internal Medicine, 15th ed.
Review of medical physiology by william F. Ganong, 20Review of medical physiology by william F. Ganong, 20
thth
ed. ed.
Fundamentals of medical physiology L prakasam Reddy 3Fundamentals of medical physiology L prakasam Reddy 3
rdrd
ed. ed.
Photographs taken from various websites. Photographs taken from various websites.