Gas Transport (series Ii)

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Rate of O2 delivery to the tissues 

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CaO2 X Q

CaO2 ([Hb] X 1.34 X % Hb satn) + (PO2 X 0.003) Types of hypoxia 

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1. HYPOXIC HYPOXIA  Most common  Characterised by a low PaO2 (hypoxaemia) →  ↓ % Hb saturation →  CaO2 ↓ (when PaO2 ≤ 60 mm Hg, CaO2 ↓↓ ) •

Inadequate O2 delivery to body tissues → hypoxia

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Rate of O2 delivery to the tissues 

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CaO2 X Q

CaO2 ([Hb] X 1.34 X % Hb satn) + (PO2 X 0.003) 2. ANAEMIC HYPOXIA 

 Can be brought about by: o ↓ [Hb] or circulating red blood cells → o ↓ O2-carrying capacity of blood o Inability of Hb to bind O2 eg.  in CO poisoning  In anaemic hypoxia, the CaO2 ↓ but the PaO2 normal (↔) •

Inadequate O2 delivery to body tissues → hypoxia

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Rate of O2 delivery to the tissues 

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CaO2 X Q

CaO2 ([Hb] X 1.34 X % Hb satn) + (PO2 X 0.003) 2. ANAEMIC HYPOXIA 

 Can be brought about by: o ↓ [Hb] or circulating red blood cells → o ↓ O2-carrying capacity of blood o Inability of Hb to bind O2 eg.  in CO poisoning  In anaemic hypoxia, the CaO2 ↓ but the PaO2 normal (↔) •

Inadequate O2 delivery to body tissues → hypoxia

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Rate of O2 delivery to the tissues 

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CaO2 X Q

CaO2 

([Hb] X 1.34 X % Hb satn) + (PO2 X 0.003)

3. STAGNANT HYPOXIA 

Arises when there is a decrease in blood flow to the tissues



Can be restricted to a limited area as a result of a local vascular spasm or localised blockage or the body may experience stagnant hypoxia in general as a result of low CO eg. o

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in severe haemorrhage

CaO2 normal & PaO2 are normal (↔)

Inadequate O2 delivery to body tissues → hypoxia

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Rate of O2 delivery to the tissues 

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CaO2 X Q

CaO2 

([Hb] X 1.34 X % Hb satn) + (PO2 X 0.003)

4. HISTOTOXIC HYPOXIA  O2 delivery to the tissues is normal but the cells are unable to use the O2 eg. o

cyanide poisoning

 CaO2 & PaO2 normal (↔)  PvO2 & CvO2 high compared to normal •

Inadequate O2 delivery to body tissues → hypoxia

EFFECTS OF HYPOXIA •

Brain – wide variety of mental symptoms eg. inability to concentrate, disorientation, nausea, sleepiness

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>15 secs. without O2 – unconscious

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5 min. without O2 → irreversible damage to brain

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O2 therapy (administration of O2) very beneficial in hypoxia due to ↓ PIO2 , hypoventilation, diffusion impairment

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Histotoxic hypoxia - not beneficial

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Stagnant hypoxia, anaemic hypoxia ( PaO2 normal) O2 therapy is of much less value (Hb nearly saturated with O2 )

CARBON MONOXIDE (CO) • Colourless, odourless gas, non-irritating gas produced during the incomplete combustion (burning) of carbon products such as petrol, coal, wood, tobacco • CO poisoning is commonly caused by motor vehicles exhaust fumes due to suicide attempts, smoke inhalation or defective indoor heaters • Smokers – higher level of carboxyhaemobgobin in blood (5 -10% COHb) • CO + Hb → carboxyhaemoglobin

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CO TOXICITY • CO competes with O2 for the heme-binding sites on haemoglobin but CO binds Hb with an affinity 200 to 250 times greater that for O2 to form carboxyhaemoglobin (COHb) →  ↓ CaO2 →  tissue hypoxia • Binding of CO to Hb causes a leftward shift in the oxyhaemoglobin dissociation curve & ↓ release of O2 →  worsens hypoxia • Moderate CO poisoning: PaO2 normal

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CaO2 ↓ in anaemia due to low [Hb]

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Compensatory processes in chronic anaemia to improve O2 delivery to tissues:  ↑ [2,3-DPG] (due to chronic hypoxia) → o HbO2 curve shifts to the right facilitates O2 release from Hb to the tissues  ↑ CO → o ↑ blood flow to the tissues

TREATMENT OF CO POISONING • Administration of 100 % O2 • Hyperbaric O2 therapy for severe CO poisoning  (100% O2 given at v. high pressure→↑ PO2 to v. high value) • ↑ amount of dissolved O2 in blood • Enhances the clearance of COHb → o Half-life of carboxyHb < 30 minutes

Rest: 200 ml CO2 produced/min from metabolism

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CO2 transported in 3 forms in blood: • As dissolved CO2 in plasma (5-10% of the blood’s total CO2 content)  Amount of dissolved CO2 directly proportional to PCO2 (Henry’s law)  (CO2 ~20x more soluble than O2 in the blood)

2. Bound to Hb as carbaminohaemoglobin & to pl proteins  (10% - 30%)  CO2 binds to amino groups of globin chains  DeoxyHb/reduced Hb has greater affinity or combines more readily wih CO2 than does HbO2

Rest: 200 ml CO2 produced/min from metabolism

3. Most CO2 transported as bicarbonate ions (HCO3-) in plasma  CO2 enters RBCs → reacts with H2O to form carbonic acid  Reactions is fast in RBC because of the presence of the enzyme carbonic anhydrase (ca) which catalyse the reaction (ca is not present in plasma)

• H2CO3 dissociates rapidly into a bicarbonate ion & H+ ion without enzyme assistance • Most HCO3- ions moves out of the erythrocytes into the plasma via a transporter that exchanges one bicarbonate for one chloride ion (chloride shift) to maintain electrical neutrality

• What happen to H+?  H+ buffered by Hb  DeoxyHb has greater affinity for H+ than does HbO2 so it binds (buffers) most of the H+  The unloading of O2 to the tissues facilitates the pick-up of H+ by Hb

• In the lungs, as systemic venous blood flows thro’ the lung capillaries, the opposite events occur (H+ & CO2 released from Hb as O2 bind to Hb HCO3- reenters the RBCs (Cl- moves into plasma (reverse Cl- shift) HCO3- & H+ combine to give H2CO3 which then dissociates into CO2 & H2O; CO2 diffuses from blood into alveoli • RBCs shrinks

SUMMARY OF ROLE OF RBCS IN CO2 TRANSPORT

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Formation of HCO3• •

RBCs have carbonic anhydrase enzyme (CA) ← ← Catalysed reaction:  H2O + CO2

→

H2CO3 → H+ + HCO3-

(2) In the systemic capillaries, Hb buffers H+ which results from hydration of CO2 DeoxyHb is a better buffer (3) Hb combines with CO2 to form carbaminohaemoglobin DeoxyHb can form more carbaminoHb

(Total blood CO2 content)

(Total blood CO2 content)

• CO2 dissociation curve  Show relationship between PCO2 of blood & the total CO2 content of blood

CO2 DISSOCIATION CURVE

CO2 DISSOCIATION CURVE

 ↑ PCO2 of blood → ↑ CO2 content of blood  blood does not saturate with CO2

CO2 DISSOCIATION CURVE

HALDANE EFFECT • Effect of PO2 of blood on CO2 dissociation curve • Deoxygenated blood (lower PO2), CO2 dissociation curve shifts to the left (upward) (greater blood CO2 content at any PCO2 of blood)

SIGNIFICANCE / IMPORTANCE OF HALDANE EFFECT (i) Haldane effect facilitates CO2 uptake at the tissues (↓ PO2 in venous blood (deoxygenated blood) shifts CO2 dissociation curve upwards ie. CO2 content of venous blood at any given PCO2 is higher)

MECHANISMS OF HALDANE EFFECT •

(deoxygenated blood (lower PO2) has greater CO2 content

(c) As blood flows thro’ tissue capillaries, PO2 ↓ → more deoxyHb:

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I.

deoxyHb forms carbaminohaemoglobin more readily than does oxyHb

II.

deoxyHb is a better buffer than oxyHb

Reaction: CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3shifted to right

• Haldane effect facilitates unloading of CO2 or CO2 release in the lungs • Rest: ~ 4 ml CO2 excreted out per 100 ml blood (52ml – 48ml)

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Haldane effect facilitates unloading of CO2 or CO2 release in the lungs

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Uptake of O2 in the lungs →  PO2 in the blood ↑ →  More oxyHb formed → facilitates release of CO2 & H+ from Hb (deoxyHb has greater affinity for CO2 & H+ than does HbO2 )

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Rest: ~ 4 ml CO excreted out per 100 ml blood (52ml – 48ml)