1. HEMOGLOBIN AND OXYGEN TRANSPORT
RESPIRATORY SYSTEM - 3
HEMOGLOBIN AND OXYGEN TRANSPORT

2. Oxygen Content of Blood

3. Structure of Hemoglobin
Normal hemoglobin contains reduced iron, Fe2+
Deoxyhemoglobin (reduced hemoglobin) also has Fe2+
Methemoglobin has Fe3+ and cannot bind O2
Carboxyhemoglobin – bound to carbon monoxide (abnormal)
Hemoglobin is normally 97% oxyhemoglobin (oxyHb)

4. Hemoglobin Concentration
Oxygen-carrying capacity of whole blood is determined by the concentration of hemoglobin
Anemia – low hemoglobin
Polycythemia – high RBC count (high altitude)
Erythropoietin controls RBC count

5. OXYHEMOGLOBIN DISSOCIATION CURVE
Y-axis = %oxyHb
Y-axis = ml O2 per 100 ml blood
X-axis = PO2 (mmHg)
Hb is 97% saturated at 100 mmHg
This is when O2 gets unloaded to tissues
At venules, PO2 = 40 mmHg
O2 unloaded to tissues is about 5 ml/100 ml of blood
Still have 75% oxyHb
Note sigmoidal curve-
b/w mmHg, unloading happens slowly
Below 40 mmHg, curve drops off rapidly

6. Effect of pH and Temperature on Oxygen Transport
BOHR EFFECT – As pH drops, affinity of O2 for Hb decreases
Low pH  graph shifts to right  greater unloading of O2
Important during exercise

7. Effect of 2,3-DPG on Oxygen Transport

9. Fetal Hemoglobin – Hb-F
Hb-F cannot bind to 2,3-DPG
Therefore, Hb-F has a higher affinity for oxygen than Hb-A (adult hemoglobin)
Therfore, oxygen is more readily transferred from maternal to fetal blood through the placenta

10. Sickle-cell Anemia

11. Myoglobin has a higher affinity for oxygen than hemoglobin

12. Carbon Dioxide Transport

13. Introduction Carbon dioxide is carried in the blood in three forms:
Dissolved in plasma (more soluble than O2)
As carbaminohemoglobin attached to an amino acid in hemoglobin
As bicarbonate ions (accounts for the majority of transport)

14. Introduction, cont Carbonic anhydrase H2O + CO2 H2CO3
Carbon dioxide readily reacts with water in the RBC of the systemic capillaries and plasma
Carbonic anhydrase is the enzyme that catalyzes the reaction to form carbonic acid at high PCO2
H2O + CO H2CO3

15. Formation of Bicarbonate and H+
Carbonic acid is a weak acid that will dissociate into bicarbonate and hydrogen ions. This reaction also uses carbonic anhydrase as the catalyst
H2CO H+ + HCO3−

16. Chloride Shift
Once bicarbonate ion is formed in the RBC, it diffuses into the plasma
H+ in RBCs attach to hemoglobin and attract Cl−.
The exchange of bicarbonate out of and
Cl− into RBCs is called the chloride shift (see next slide). (chloride moves into the RBC because it’s more positively charged due to H+)

17. Carbon Dioxide Transport & the Chloride Shift

18. Bohr Effect
Bonding of H+ to hemoglobin lowers the affinity for O2 and helps with unloading.
This allows more H+ to bind, which helps the blood carry more carbon dioxide.

19. Reverse Chloride Shift
In pulmonary capillaries, increased PO2 favors the production of oxyhemoglobin.
This makes H+ dissociate from hemoglobin and recombine with bicarbonate to form carbonic acid:
H+ + HCO3− H2CO3
Chloride ion diffuses out of the RBC as bicarbonate ion enters.

20. Reverse Chloride Shift, cont
In low PCO2, carbonic anhydrase converts carbonic acid back into CO2 + H2O:
H2CO CO2 + H2O
CO2 is exhaled.

21. Reverse Chloride Shift in the Lungs

22. Acid- Base Balance of the Blood

23. Principles of Acid-Base Balance
Maintained within a constant range by the actions of the lungs and kidneys
pH ranges from 7.35 to 7.45.
Since carbonic acid can be converted into a gas and exhaled, it is considered a volatile acid; regulated by breathing.
Nonvolatile acids (lactic, fatty, ketones) are buffered by bicarbonate; can not be regulated by breathing, but rather the kidneys

24. Bicarbonate as a Buffer
Bicarbonate ion is a weak base and is the major buffer in the blood
excess H+ + HCO3-  H2CO3
Buffering cannot continue forever because bicarbonate will run out.
Kidneys help by releasing H+ in the urine and by producing more bicarbonate.

25. Bicarbonate as a Blood Buffer

26. Blood pH: Acidosis Acidosis: when blood pH falls below 7.35
Respiratory acidosis: caused by hypoventilation; rise of CO2 which increases H+ (lowers pH)
Metabolic acidosis: caused by excessive production of acids or loss of bicarbonate (diarrhea)

27. Blood pH: Alkalosis Alkalosis: when blood pH rises above 7.45
Respiratory alkalosis: caused by hyperventilation; “blow off” CO2, H+ decreases, pH increases
Metabolic alkalosis: caused by inadequate production of acids or overproduction of bicarbonates, loss of digestive acids from vomiting
Respiratory component of blood pH measured by plasma CO2
Metabolic component measured by bicarbonate

28. Terms Used in Acid Base Balance

29. Classification of Metabolic & Respiratory Components of Acidosis & Alkalosis

30. Henderson-Hasselbalch Equation
Normal blood pH is maintained when bicarbonate and CO2 are at a ratio of 20:1.
HCO3−
pH = log
0.03PCO2
Respiratory acidosis or alkalosis occurs with abnormal CO2 concentration
Metabolic acidosis or alkalosis occurs with abnormal bicarbonate concentration

31. Ventilation and Acid-Base Balance
Ventilation controls the respiratory component of acid-base balance.
Hypoventilation: Ventilation is insufficient to “blow off” CO2. PCO2 is high, carbonic acid is high, and respiratory acidosis occurs.
Hyperventilation: Rate of ventilation is faster than CO2 production. Less carbonic acid forms, PCO2 is low, and respiratory alkalosis occurs.

32. Ventilation and Acid-Base Balance, cont
Ventilation can compensate for the metabolic component.
A person with metabolic acidosis will hyperventilate; “blow off” CO2, H+ decreases, pH rises
A person with metabolic alkalosis will hypoventilate; slow respiration, build up CO2, H+ increases, pH lowers

33. Effect of Lung Function on Blood Acid-Base Balance

34. IX. Effect of Exercise and High Altitude on Respiratory Function

35. Ventilation During Exercise
Exercise produces deeper, faster breathing to match oxygen utilization and CO2 production.
Called hyperpnea
Neurogenic and humoral mechanisms control this.

36. Proposed Neurogenic Mechanisms
Sensory nerve activity from exercising muscles stimulates respiration via spinal reflexes or brain stem respiratory centers.
Cerebral cortex stimulates respiratory centers.
Helps explain the immediate increase in ventilation at the beginning of exercise

37. Humoral Mechanisms
Rapid and deep breathing continues after exercise is stopped due to humoral (chemical) factors.
PCO2 and pH differences at sensors
Cyclic variations that are not detected by blood samples that affect chemoreceptors

38. Effect of exercise on arterial blood gases & pH

39. Lactate Threshold
Ventilation does not deliver enough O2 at the beginning of exercise.
Anaerobic respiration occurs at this time.
After a few minutes, muscles receive enough oxygen.
If heavy exercise continues, lactic acid fermentation will be used again.
The lactate threshold is the maximum rate of oxygen consumption attained before lactic acid levels rise.

40. Lactate Threshold, cont
Occurs when 50−70% maximum oxygen uptake is reached
Due to aerobic limitations of the muscles, not the cardiovascular system (still at 97% oxygen saturation)
Endurance exercise training increases mitochondria and Krebs cycle enzymes in the muscles

41. Changes in Respiratory Function During Exercise

42. Acclimation to High Altitude
Adjustments must be made to compensate for lower atmospheric PO2.
Changes in ventilation
Hemoglobin affinity for oxygen
Total hemoglobin concentration

43. Blood Gas Measurements at Different Altitudes

44. Changes in Ventilation
Hypoxic ventilatory response: Decreases in PO2 stimulate the carotid bodies to increase ventilation.
Hyperventilation lowers PCO2, causing respiratory alkalosis.
Kidneys increase urinary excretion of bicarbonate to compensate.
Chronically apoxic people produce NO in the lungs, a vasodilator that increases blood flow.
NO bound to sulfur atoms (SNOs) in hemoglobin may stimulate the rhythmicity center in the medulla.

45. Affinity of Hemoglobin for Oxygen
Oxygen affinity decreases, so a higher proportion of oxygen is unloaded.
Occurs due to increased production of 2,3-DPG
At extreme high altitudes, effects of alkalosis will override this, and affinity for oxygen will increase.

46. Increased Hemoglobin Production
Kidney cells sense decreased PO2 and produce erythropoietin.
This stimulates bone marrow to produce more hemoglobin and RBCs.
Increased RBCs can lead to polycythemia, which can produce pulmonary hypertension and more viscous blood.

47. Changes During Acclimatization to High Altitude

48. Respiratory Adaptations to High Altitude