CH. 22 - Respiratory System (Part 3)

Systemic Gas Exchange

The unloading of O2 and loading of CO2 at the systemic capillaries

CO2 Loading in Systemic Gas Exchange

• CO2 diffuses into the blood

• Carbonic anydrase in RBC catalyzes CO2 + H2O → H2CO3 → HCO3- + H+

• Chloride shift happens

  • We put a bicarbonate ion into the plasma and put a Cl- ion into the rbc

  • Keeps reaction proceeding

  • H+ binds to hemoglobin

Oxygen Unloading in Systemic Gas Exchange:

• As H+ ions bind to hemoglobin, we get less affinity for O2

• as we lose O2, we are more likely to lose more O2 from that hemoglobin

• hemoglobin arrives at the capillaries 97% saturated with O2, and leaves 75% saturated

  • difference is caused by the utilization coefficient:

    • we typically lose 22% of O2 in the capillaries

  • Venous reserve:

    • the O2 remaining in the blood after it passes through capillary beds

How do the reactions in the lungs for gas exchange compare to the reactions in systemic gas exchange?

Reactions that occur in the lungs are reverse of systemic gas exchange

CO2 Unloading in Alveolar Gas Exchange

• As hemoglobin loads O2 from the alveoli, its affinity for H+ decreases

• Reverse chloride shift happens

  • bicarbonate diffuses back into the RBC in exchange for Cl-

• H+ dissociates from hemoglobin and binds with bicarbonate in the RBC

• carbonic anhydrase turns carbonic acid into CO2 and water

• the CO2 diffuses into the alveoli to be exhaled

Hemoglobin unloads O2 to. . .

match the metabolic needs of different states of activity of the tissues

4 factors that adjust the rate of oxygen unloading to match metabolic need:

1. Ambient PO2

2. Ambient pH (Bohr effect)

3. Temperature

4. Biphosphoglycerate (BPG)

How ambient PO2 adjusts the rate of oxygen unloading:

active tissue has lower PO2

• the lower the ambient partial pressure of oxygen, the more likely we are to release O2

How ambient pH adjusts the rate of oxygen unloading:

active tissue has higher levels of CO2

• the more CO2 in blood, the more H ions, making pH lower and more acidic

• the lower the blood pH, the more we unload O2

How temperature adjusts the rate of oxygen unloading:

Active tissue has a higher temperature

• as body temp goes up, rate of unloading O2 goes up

• as body temp goes down, the rate of O2 unloading goes down

How bisphosphoglycerate (BPG) adjusts the rate of oxygen unloading:

Erythrocytes produce BPG

• can bind to hemoglobin

• as it binds, it causes O2 to be unloaded

  • causes hemoglobin to change shape so it unloads O2

• we get more BPG with increases in body temp, thyroxine, growth hormone, testosterone, and epinephrine

What are the set points for arterial blood pH, PCO2, and PO2?

• pH: 7.35-7.45

• PCO2: 40 mmHg

• PO2: 95 mmHg

How do we maintain and monitor these arterial blood levels?

• These arterial blood levels are maintained by adjustments to the rate and depth of breathing

• to monitor these factors, we have chemoreceptors in the PNS and CNS that monitor chemistry of the blood and CSF

• blood pH influences breathing/respiratory rhythm the most

• least important is blood oxygen levels

What produces the respiratory response to pH changes?

• Central Chemoreceptors

  • produce 75% of the change in respiration caused from the pH shift

  • CO2 crosses the BBB and reacts with water in the cerebrospinal fluid to produce carbonic acid

  • the H+ ions from carbonic acid strongly stimulates the chemoreceptors

• Peripheral Chemoreceptors

  • produces 25% of the change in respiration in response to pH changes

  • H+ ions also stimulate these chemoreceptors

Acidosis Vs. Alkalosis

Acidosis: blood pH lower than 7.35

Alkalosis: blood pH higher than 7.45

Hypocapnia Vs. Hypercapnia

Hypocapnia: the pressure of CO2 is less than 37 mmHg

• Most common cause of alkalosis

Hypercapnia: the pressure of CO2 is greater than 43 mmHg

• most common cause of acidosis

Normal pressure of CO2: 37-43 mmHg

Respiratory Acidosis and Alkalosis

pH imbalances resulting from a mismatch between the rate of pulmonary ventilation and the rate of CO2 production

• breathing in and out too much or too little relative to CO2 production

What is a corrective homeostatic response to acidosis?

hyperventilation

• blowing off CO2 faster than the body can produce it

• Pushes the CO2 reaction to the left

• reduces H+ ions, raising pH back to normal

What is a corrective homeostatic response to alkalosis?

Hypoventilation

• allows CO2 to accumulate in body fluids faster than we can exhale it

• Shifts the CO2 reaction to the right

• Raises number of H+ ions, lowering the pH back to normal

Ketoacidosis

Acidosis brought about by burning fat very quickly, releasing acidic ketone bodies

• a classic symptom of type 1 diabetes

• causes Kussmaul Respiration

  • hyperventilating to partially compensate for the fact that our metabolism is putting too many ketone bodies in our blood stream

• high ketone bodies makes sweet urine

Effects of CO2 on Breathing (Direct and Indirect)

Direct:

• increase of CO2 at the beginning of exercise can directly stimulate peripheral chemoreceptors and trigger an increase in ventilation faster than central chemoreceptors

Indirect:

• through pH shifts

PO2 has ___ effect on respiration

little

Chronic Hypoxemia

chronically low O2

• PO2 is less than 60 mmHg, which can significantly stimulate ventilation

• Causes hypoxic drive:

  • respiration driven more by low O2

• Can be triggered by emphysema, pneumonia, and high elevations

Causes of Increased Respiration During Exercise:

• When the brain sends motor commands to the muscles, it also sends this information to the respiratory centers

  • these centers will increase ventilation in anticipation of the needs of the muscles

• exercise stimulates propioreceptors of muscles and joints

  • they increase breathing when informed that muscles are moving

  • the increase in breathing keeps blood gas values at normal levels

Senescence of the Respiratory System

• Declining pulmonary ventilation

  • Costal cartilages become less flexible

  • Lungs have less elastic tissue and fewer alveoli

• Elderly are less able to clear lungs of irritants or pathogens

  • More susceptible to respiratory infection

  • their mucociliary escalator slows down, leading to pneumonia

    • pneumonia causes more deaths than any other infectious disease

• Chronic obstructive pulmonary diseases

  • Emphysema and chronic bronchitis more common

  • Takes a lifetime of degenerative change for these diseases to happen

  • Contribute to hypoxemia and hypoxic degeneration of other organ systems

Hypoxia

oxygen deficiency in a tissue, or the inability to use oxygen

• if not enough gas exchange, we get low blood O2, causing low tissue O2

• cyanosis is a sign of hypoxia

Hypoxemic Hypoxia

state of low arterial PO2

• usually due to inadequate pulmonary gas exchange

• can also be due to oxygen deficiency at high elevations or impaired ventilation

  • drowning, aspiration, respiratory arrest, degenerative lung diseases

Ischemic Hypoxia

inadequate circulation of blood

• not enough blood flow through the lungs

• often caused by congestive heart failure and blockages of vessels

Anemic Hypoxia

due to anemia, resulting from the inability of the blood to carry adequate oxygen

Histotoxic Hypoxia

metabolic poisons such as cyanide prevent tissues from using oxygen

• causes cyanosis

Oxygen Toxicity

develops when pure O2 is breathed at 2 ATM or higher for a short time

• this generates free radicals and H2O2 (peroxide)

• destroys enzymes

• damages nervous tissue

Hyperbaric Oxygen

Formerly used to treat premature infants

• were put in a chamber with elevated O2

• it caused more harm than good, so it is not used anymore

Chronic obstructive pulmonary disease (COPD)

long-term obstruction of airflow and substantial reduction in pulmonary ventilation

• Major COPDs are chronic bronchitis and emphysema

  • Almost always associated with smoking

  • Other risk factors: air pollution, occupational exposure to airborne irritants, hereditary defects

• COPD reduces vital capacity

• COPD causes: hypoxemia, hypercapnia, and respiratory acidosis

  • Hypoxemia stimulates erythropoietin release from kidneys, and leads to polycythemia

Chronic Bronchitis

• Severe inflammation of the lower respiratory tract

• Goblet cells enlarge and produce excess mucus

• Immobilized cilia fail to remove mucus

• Thick, stagnant mucus forms, which is ideal for bacterial growth

• Smoke compromises alveolar macrophage function

• Develop a chronic cough to bring up sputum (thick mucus and cellular debris)

• Chronic bronchitis almost always lead to pneumonia

• Symptoms include hypoxemia and cyanosis

Emphysema

• Alveolar walls break down and merge together

  • Lung has fewer and larger spaces

  • Much less respiratory membrane for gas exchange

• Lungs become fibrotic and less elastic

  • Lungs become flabby and form cavities with large spaces

• Air passages collapse

  • Obstructs outflow of air

  • Air trapped in lungs, causing person becomes to be barrel-chested

• Weakens thoracic muscles

  • Spend three to four times the amount of energy just to breathe

Cor Pulmonale

thickening of the right ventricle of the heart

• happens when the blood entering the heart is more than the blood exiting due to an obstruction

Lung Cancer

Accounts for more deaths than any other form of cancer

• Most important cause is smoking (at least 60 carcinogens)

• Both tobacco and marijuana have these carcinogens and cause lung cancer

Squamous-Cell Carcinoma

• Most common form of lung cancer

• Begins with the transformation of the bronchial epithelium into stratified squamous from ciliated pseudostratified epithelium

• Dividing cells invade the bronchial wall, cause bleeding lesions

• Dense swirls of keratin replace the respiratory tissue

Adenocarcinoma

Originates in mucous glands of lamina propria of the lungs

Small-Cell (oat cell) Carcinoma

• Least common, most dangerous

• Named for clusters of cells that resemble oat grains

• Originates in primary bronchi, then invades the mediastinum, and metastasizes quickly to other organs