High altitude disease complication

Disorders of ventilation to

perfusion matching in lungs

C + O₂ CO₂

O₂ CO₂

Saccharides Fats Proteins

cell

+ O₂ CO₂

2 CO₂

H₂O

mitochondrion

mitochondrion

mitochondrion Endoplasmic

reticulum

peroxisome

mitochondrion nucleus

lysosome

Golgi

Apparatus vesicle

Plasma membrane

pO2 kidneys erythropoetin

Bone marrow

erythropoesis

Saccharides Fats Proteins

cell

+ O₂ CO₂ CO₂

H₂O

mitochondrion

mitochondrion

Histotoxic Hypoxia

Respiratory Hypoxia High Altitude Hypoxia

O₂

Circulatory Hypoxia (ischemic)

Hypoxia from Anemia

pO2 kidneys erythropoetin

Bone marrow

erythropoesis

Saccharides Fats Proteins

cell

+ O₂ CO₂ CO₂

H₂O

mitochondrion

mitochondrion

O₂

High Altitude Hypoxia

0 100 200 300 400 500 600 700 800

0 1000 2000 3000 4000 5000 6000 7000 8000 9000 10000

Pokles barometrického tlaku s výškou

Climbing

Barometric pressure drop

0 20 40 60 80 100 120 140 160

0 1000 2000 3000 4000 5000 6000 7000 8000 9000 10000

PO2 v insp. vzduchu

Climbing

Barometric pressure drop

Fall PO2 in inspired air

High Altitude Hypoxia Climbing

Barometric pressure drop

Fall PO2 in inspired air

Fall alveolar PO2

PO2 v

inspir. vzd uchu

PAO2 - aklimatizovaní PAO2 – akutní expozice

PAO2 – fully acclimated

PAO2 – acute exposition PO2 v inspir. vzduchu

Fall arterial PO2

Climbing

Barometric pressure drop

Fall PO2 in inspired air

Fall alveolar PO2

Fall arterial PO2

Hyperventilation

Hypocapnia

Alkalosis Shift of oxyhemoglobin

saturation curve to left Impairment of oxygen

release in tissue

pO2 SO2

O2 release

O2 release

Respiratory centre stimulation

High Altitude Hypoxia Climbing

Barometric pressure drop

Fall PO2 in inspired air

Fall alveolar PO2

Fall arterial PO2

Hyperventilation

Hypocapnia

Alkalosis Shift of oxyhemoglobin

saturation curve to left Impairment of oxygen

release in tissue Blood

acidifacion Shift of oxyhemoglobi

n saturation curve to right

Increase of oxygen release in tissue

pO2 SO2

O2 release

O2 release

Respiratory centre stimulation

Kidney response to alkalemia:

increase of bicarbonate

excretion

ADAPTATION Hypoxia improvement

Climbing

Barometric pressure drop

Fall PO2 in inspired air

Fall alveolar PO2

Fall arterial PO2

Hyperventilation

Hypocapnia

Alkalosis Shift of oxyhemoglobin

saturation curve to left Impairment of oxygen

release in tissue

Respiratory centre stimulation

Kidney response to alkalemia:

increase of bicarbonate

excretion

ADAPTATION

Decrease bicarbonate resorption in proximal tubule,

bicarbonate

excretion increases Acetazolamid Blood

acidifacion Shift of oxyhemoglobi

n saturation curve to right

Increase of oxygen release in tissue

Hypoxia improvement

High Altitude Hypoxia Climbing

Barometric pressure drop

Fall PO2 in inspired air

Fall alveolar PO2

Fall arterial PO2

Hyperventilation

Hypocapnia

Alkalosis Shift of oxyhemoglobin

saturation curve to left Impairment of oxygen

release in tissue

Respiratory centre stimulation

Kidney response to alkalemia:

increase of bicarbonate

excretion

ADAPTATION

Hyperventilation water loss Dehydration

Hemoconcentration Hematocrit

increase

Stimulation of hemopoiesis

Erythropoetin production Blood

acidifacion Shift of oxyhemoglobi

n saturation curve to right

Increase of oxygen release in tissue

Hypoxia improvement

HEADACHE, INSOMNIA, ANOREXIA, TIREDNESS

Hypocapnia Hypoxia

Brain

vasiconstriction (hypocapnic brain

vasoconstriction lasts only 2-3 days)

Brain vasodilatation Flow increase Intracerebral hypertension

High Altitude Hypoxia

Mount Everest climbing

High altitude disease complication

HIGH ALTITUDE PULMONARY EDEMA

HIGH ALTITUDE BRAIN EDEMA

RIGHT VENTRICULAR INSUFFICIENCY

High Altitude Hypoxia

Alveolar hypoxia

HIGH ALTITUDE PULMONARY EDEMA

Alveolar hypoxia

HIGH ALTITUDE PULMONARY EDEMA

inferior

vasoconstriction Pressure

Unevennes hypoxic rise

vasoconstriction of lung arterioles Increase of pulmonary

arterial pressure

Hypoxie výšková

Alveolar hypoxia

HIGH ALTITUDE PULMONARY EDEMA

inferior

vasoconstriction Pressure

rise

Pressure

Unevennes hypoxic rise

vasoconstriction of lung arterioles Increase of pulmonary

arterial pressure

Pressure rise in unprotected capillaries

Alveolar hypoxia

HIGH ALTITUDE PULMONARY EDEMA

inferior

vasoconstriction Pressure

rise

Pressure rise

Edema

Unevennes hypoxic

vasoconstriction of lung arterioles Increase of pulmonary

arterial pressure

Pressure rise in unprotected capillaries

Exudation

Hypoxie výšková

Alveolar hypoxia Unevennes hypoxic

vasoconstriction of lung arterioles Increase of pulmonary

arterial pressure

Pressure rise in unprotected capillaries

Exudation Basement membrane

damage Neutrophiles activation

Inflamatory factors release

Thrombocyte activation

Fibrine thrombi

inferior

vasoconstriction Pressure

rise

Pressure rise

Edema

HIGH ALTITUDE PULMONARY EDEMA

Alveolar hypoxia

HIGH ALTITUDE LUNG ADAPTATION

High Altitude Hypoxia

Alveolar hypoxia

HIGH ALTITUDE LUNG ADAPTATION Unevennes hypoxic

vasoconstriction of lung arterioles Increase of pulmonary

arterial pressure

inferior

vasoconstriction Pressure

rise

Alveolar hypoxia

Gradual muscular hypertrophy even in capillaries with inferior

vasoconstriction

Pulmonary vasculature remodelation – pulmonary

vasoconstriction is uniform All capillaries are protected from high pressure

transmission from arteries to capillaries

HIGH ALTITUDE LUNG ADAPTATION

inferior

vasoconstriction Pressure

Unevennes hypoxic rise

vasoconstriction of lung arterioles Increase of pulmonary

arterial pressure

High Altitude Hypoxia

Alveolar hypoxia

Gradual muscular hypertrophy even in capillaries with inferior

vasoconstriction

Pulmonary vasculature remodelation – pulmonary

vasoconstriction is uniform All capillaries are protected from high pressure

transmission from arteries to capillaries

HIGH ALTITUDE LUNG ADAPTATION Unevennes hypoxic

vasoconstriction of lung arterioles Increase of pulmonary

arterial pressure

inferior

vasoconstriction Pressure

rise

COMPLICATION:

RIGHT VENTRICULAR INSUFFICIENCY

Hypoxia

Big stimulus for vasodilatation and hyperemia Hypocapnia

Hypocapnic stimulus for

brain

vasoconstrictio n

Hypocapnic stimulus for

brain

vasoconstrictio n lasts only 2-3-

days

Increase of brain vascular

flow

HIGH ALTITUDE BRAIN EDEMA

1. Ventilation

CO₂ O₂

CO₂

Respiratory Hypoxia (Hypoxic) High Altitude Hypoxia

O₂

2. Perfusion

3. Diffusion

What is the function of lungs?

Alveolus

• Ventilation – mechanical function of the lung – get air in and out

• Perfusion with blood – get blood in and out

• Diffusion – get gas molecules from air to blood and back

• Matching of ventilation and perfusion

Possible respiratory system disturbances

• // ventilation

• //

• // distribution of ventilation and per-fusion

= ventilation perfusion mismatch

• // diffusion

•

processes.

•

– 1. In the effector part (lungs, resp. muscles for ventilation, heart for perfusion)

– 2. In the regulator part (sensors, CNS eg. in uremia, liver in hepatopulmonary

syndrome)

The overall measure of respiratory system function

• pO2 & pCO2 in arterial blood - („ Astrup “)

• O2 solubility in water is low => need of Hemoglobin

• pO2 = 13,3 kPa = 100 Torr

• pCO2 = 5,3 kPa = 40 Torr

(1 kPa = 10 cm H2O = 7,6 mmHg or Torr)

External intecost. m.

Internal intercost. m.

Internal intercost. m.

inspiration

expiration

Alveolar ventilation

VE=VD+VA

FRC = Function residual capacity

Alveolar ventilation

VCO2 = F

CO2 * VA VA = VCO2/F

CO2

VA = k

×VCO2/P

CO2

P

CO2

= 0,863*VCO2

/VA

P

CO2 = F

CO2×Barometric pressure

P

CO2 = k

×VCO2/VA

STPD BTPS

P×V (P-PH₂O)×VBTPS 760×V^BTPS T 273+ t°= R patient = 273

2

F_ACO₂×

VCO₂

VA

VCO₂

PaCO2

VA

VA

P

CO2

= 0,863*VCO2

/VA

E 2 A 2

VO₂=V_iO₂-V_EO₂

VA

i 2 i 2

V_iO₂V_EO₂

F

O

=F

O

- VO

/VA VO

=F

O

×VA - F

O

×VA

P

O

=P

O

- k×VO

/VA

PACO2 PAO2

PaCO2

VA PaO2

VA

pCO

pO

pCO

pO

VE=VD+VA

pCO

Respir. Centre

pO

Alveolar Ventilation Controls Rate of Breathing by Influencing pCO2 and pO2

VA

Only whenpO ²

is low

Why the airplane flies?

Why the airplane flies?

Why the airplane flies?

Narrowing of bronchiole (bronchoconstriction, mucus…)

Inspiration – the narrowing is opposed by neg. introthoratic pressure

Narrowing of bronchiole (bronchoconstriction, mucus..)

Expiration – nothing opposes the narrowing of a bronchiole

Narrowing of a bronchiole (bronchoconstriction, mucus..)

Narrowing of a bronchiole (bronchoconstriction, mucus..)

Forceful expiration - leads to worsening of the obstruction

Air Captioning – premature closure of bronchioli

The trapped air The air trapped in alveoli during

expiration exerts pressure on the alveolar membrane

Air captioning

The alveolus doesn’t manage to empty itself, thus, alveolar

ventilation decreases Norm

VA End of expiration

End of inspiration

norm emphysema

VD

VD VA

Tendency to alveolar

membrane destruction and evolution of emphysema bullae, thus enlarging the dead space

Non-emphysematous lung

VE = VD + VA

VE =

VD

VE = VD + VA

Panlobular emphysema

VE =

VD

VE = VD + VA

VA

pCO

pO

pCO

pO

VE=VD+VA

pCO

Respir. Centre

pO

Alveolar Ventilation Controls Rate of Breathing by Influencing pCO2 and pO2

VA

Only whenpO ²

is low

emphysema compensation

Emphysematous form of the chronic obstructive lung disease

normal

pCO

normal

pO

VD

VE = VD + VA

VE = VD ^{+ VA}

Normalization of VA

pCO

pO

„pink puffers“

Normal P_aO₂ – no hypoxia (until total resp. failure)

Feeling of dyspnoea Greater VE to bring to normal VA

Greater volume must be ventilated per minute Increased respiratory work

Norm Emphysema

VD VA

obstruction compensation

Obstructive form of the chronic obstructive lung disease

normal

pCO

pO

VE = VD + VA

VE = ^VD +

Compensatory increase VA

pCO

pO

„blue bloaters“

Normal P_aCO₂, lower PaO₂ – hypoxia Increased VE in order to increase the VA

obstruction

Alveolar Hypoventilation

VA

obstruction compensation

Obstructive form of the chronic obstructive lung disease

normal

pCO

pO

VE = VD + VA

VE = ^VD +

Compensatory increase of VA

pCO

pO

Normal P_aCO₂, decreased PaO₂ – hypoxia Increased VE in order to increase VA

Why pCO₂ “manages”

to normalize and pO₂ not?

„blue bloaters“

obstruction

alveolar hypoventilation

VA

obstruction

pCO

pO

VA = (VA1 + VA2)

VE = VD + (VA1+VA2) VE = VD + ( ^VA1 +

VA2

VE = VD + VA

Hypoventilated alveolus

pCO

pO

Hyperventilated alveolus

VA

VA

VA

VA

pO

pCO

pCO

pO

Obstructive form of the chronic obstructive lung disease

pCO

pO

VE = VD + ( VA1 +

VA2

Hypoventilated alveolus

pCO

pO

Hyperventilated alveolus

VA

VA

VA

VA

VA

VA

Norma

pO₂ Total O₂

pO₂

VA

Norma

pCO₂ Total CO₂

pCO₂ pO₂

pCO₂

pO

pCO

pCO

pO

Obstructive form of the chronic obstructive lung disease

pCO

pO

VE = VD + ( VA1 +

VA2

Hypoventilated alveolus

pCO

pO

Hyperventilated alveolus

VA

VA

VA

VA

VA

VA

Norma

pO₂ Total O₂

pO₂

VA

Norma

pCO₂ Total CO₂

pCO₂ norm.

pO₂ pCO₂

Respir. centre

compensation

VE = ^VD +

VA2

pO

pCO

pO

pCO

VA VA

Compensatory increase of VA1, VA2

pCO₂ norm.

pO₂

Obstructive form of the chronic obstructive lung disease

pCO

pO

VE = VD + ( VA1 +

VA2

Hypoventilated alveolus

pCO

pO

Hyperventilated alveolus

VA

VA

VA

VA

pO₂ pCO₂

Respir. centre

compensation

VE = ^VD +

VA2

pO

pCO

pO

pCO

VA VA

Compensatory increase of VA1, VA2

pCO₂ norm.

pO₂

„blue bloaters“

Obstructive form of the chronic obstructive lung disease

pCO

pO

VE = VD + ( VA1 +

VA2

Hypoventilated alveolus

pCO

pO

Hyperventilated alveolus

VA

VA

VA

VA

pO₂ pCO₂

Respir. centre

compensation

VE = ^VD +

VA2

pO

pCO

pO

pCO

VA VA

Compensatory increase of VA1, VA2

pCO₂ norm.

pO₂

„blue bloaters“

Arteriolar

vasoconstriction in hypoventilated alveoli

Precapillary pulmonary

hypertension Cor pulmonale Right heart insufficiencyy

Edema Decrease inflow

of hypoxic blood

Obstructive form of the chronic obstructive lung disease

Partial respiratory insufficiency

pCO

pO

VE = VD + ( VA1 +

VA2

Hypoventilated alveolus

pCO

pO

Hyperventilated alveolus

VA

VA

VA

VA

pO₂ pCO₂

Respir. centre

compensation

VE = ^VD +

VA2

pO

pCO

pO

pCO

VA VA

Compensatory increase of VA1, VA2

pCO₂ norm.

pO₂

Partial respiratory insufficiency

Hyperventilated alveoli are able to maintain normal pCO

level, but they are not keep up normal level of pO

, therefore

.

Patient suffer from normocapnia

a hypoxia.

pCO

pO

VE = VD + ( VA1 +

VA2

Hypoventilated alveolus

pCO

pO

Hyperventilated alveolus

VA

VA

VA

VA

pO₂ pCO₂

Respir. centre

compensation

VE = ^VD +

VA2

pO

pCO

pO

pCO

VA VA

Compensatory increase of VA1, VA2

pCO₂ pO₂

Global respiratory infufficiency

Hyperventilated alveoli are unable to maintain normal pCO

level,

. Pacient suffer from both hypercapnia a

hypoxia.

Global respiratory insufficiency

Ventilation-perfusion

VA/Q

VA/Q

Ventilation-perfusion

VA/Q

VA/Q

Ventilation-perfusion

VA ^/

VA/Q

Dead space

Ventilation-perfusion

VA

/Q

VA

/Q

Right-left shunt

hypoxia

interstitium

Starling equilibrium in pulmonary capillaries

Na

kapilára

Lymph. vessel

Hydraulic pressures (torr)

+7 -6

+13

Oncotic pressures (torr)

-28 -12 -16

-4

+2

1

interstitium

2 3

1. – ISF volume increase

Defensive mechanisms against pulmonary edema

Rise oc capillary reapsorbtion

Dilution – drop of ISFoncotic pressure

Rise of hydraulic ISF pressure

2. – increase of ISF volume ISF – storage for edematous fluid 3. – rise of lymhatic flow

Na

Left atruim pressure Filtration to alveoli

10 20

5

blood capillary

Lymph. vessel

ARDS

Acute Respiratory Distress Syndrome ARDS

Tlak v levé síni

10 20

5

ARDS

Acute respiratory distress + risk factor (infection, aspiration, pankreatitis, trauma) Hypoxemia

BIlateral pulmonary inflitration on RTG

Normal right atrial pressure (pulmonary wedge pressure< 18 torr)

Acute Respiratory Distress

Syndrome ARDS

Acute Respiratory Distress

Syndrome ARDS

Acute Respiratory Distress

Syndrome ARDS

Penetration of protein rich fluid Deposits of fibrine (hyaline membanes)

interstitium

Na

Blood capillary

Lymphatic vessel

Entdothelium activation Adhesion of thrombocytes

Activation of coagulation – inhibition of fibrinolysis Neutrophyles activation

Neutrophyles migratio Inflammatory activation of alveolar cells

Surfactant production damage

Activation of alveolar macrophages Collapse of alveoli

VA/Q

hypoxia

Acute Respiratory Distress

Syndrome ARDS

pO2 ledviny erytropoetin

Kostní dřeň

erytropoeza

Cukry Tuky Bílkoviny

buňka

+ O₂ CO₂ CO₂

H₂O

mitochondrie

mitochondrie

O₂

O₂/CO₂ O₂/CO₂

pO2 kidney erythropoetin Bone marrow

erythropoesis

Cell

+ O₂ CO₂ CO₂

H₂O

mitochondrie

O₂

O₂/CO₂ O₂/CO₂

Erytropoeza

Saccharides Fats Proteins

mitochondrion

VO₂

cellular PO₂

2

VO₂

Critical point

VO₂

cellular PO₂ O₂

VO₂

Critical point VO₂

End capillary PO₂

2

VO₂ Cellular PO₂

3,5kPa 5kPa Critical point

norm

pO2 kidney erythropoetin Bone marrow

erythropoesis

cell

+ O₂ CO₂ CO₂

H₂O

mitochondrie

O₂

O₂/CO₂ O₂/CO₂

Saccharides Fats Proteins

mitochondrion