2. MODERATE EXERCISE

3. SEVERE EXERCISE

EFFECTS OF EXERCISE ON THE CARDIOVASCULAR SYSTEM

1. ON BLOOD

2. ON BLOOD VOLUME

• i. Fluid loss
• ii. Reduced blood volume
• iii. Hemoconcentration
• iv. In severe cases, even dehydration

3. ON HEART RATE

• In moderate exercise, heart rate increases up to 180 beats/minute.
• In severe exercise, it reaches 240-260 beats/minute.

• ii. Increased carbon dioxide tension - acts through medullary centers
• iii. Rise in body temperature - acts on cardiac centers via the hypothalamus; also directly stimulates the SA node
• iv. Circulating catecholamines - secreted in large quantities during exercise

4. ON CARDIAC OUTPUT

• Cardiac output increases up to 20 L/minute in moderate exercise and up to 35 L/minute in severe exercise.
• This increase is directly proportional to the increase in oxygen consumed during exercise.

• Heart rate increases due to vagal withdrawal.
• Stroke volume increases due to a greater force of contraction.

5. ON VENOUS RETURN

6. ON BLOOD FLOW TO SKELETAL MUSCLES

• At rest: 3-4 mL/100 g of muscle/minute
• Moderate exercise: 60-80 mL/100 g/minute
• Severe exercise: 90-120 mL/100 g/minute

• i. Hypercapnea
• ii. Hypoxia
• iii. Potassium ions
• iv. Metabolites like lactic acid
• v. Rise in temperature
• vi. Adrenaline from the adrenal medulla
• vii. Increased sympathetic cholinergic activity

7. ON BLOOD PRESSURE

• Systolic pressure increases (due to increased heart rate and stroke volume)
• Diastolic pressure is not altered (peripheral resistance is not affected)

• Systolic pressure increases enormously
• Diastolic pressure decreases (due to decreased peripheral resistance caused by vasodilatation from metabolites)

• Peripheral resistance increases
• Both systolic and diastolic pressure increase

Blood Pressure After Exercise

HYPOXIA

• Costanzo Physiology 7th Edition
• Ganong's Review of Medical Physiology, 26th Edition

TYPES OF HYPOXIA (Classic 4-Type System)

1. Hypoxic Hypoxia (Hypoxemia)

• The PaO2 (oxygen level in arterial blood) is reduced
• This lowers the percentage of hemoglobin saturated with O2
• Since O2-hemoglobin is the main form of oxygen carried in blood, less of it means less total O2 delivered to tissues
• Causes:
  • High altitude (low atmospheric O2)
  • Pneumonia and other lung diseases
  • Right-to-left cardiac shunts (e.g., Tetralogy of Fallot, VSD, ASD)
  • Hypoventilation

2. Anemic Hypoxia

• PaO2 is normal, but the amount of hemoglobin available to carry O2 is reduced
• As blood passes through capillaries and the usual amount of O2 is removed, venous PO2 drops more than normal
• Causes:
  • Anemia (reduced hemoglobin concentration)
  • Carbon monoxide (CO) poisoning - CO binds hemoglobin with 210x greater affinity than O2, forming carboxyhemoglobin (COHb) which cannot carry O2; also shifts the O2-hemoglobin curve to the left so remaining hemoglobin releases O2 poorly
  • Note: CO poisoning is classified as anemic hypoxia because the O2-carrying capacity is reduced, even though total hemoglobin is unchanged

3. Ischemic (Stagnant) Hypoxia / Circulatory Hypoxia

• PaO2 is normal, but blood flow to tissues is too slow or reduced
• Tissues extract more O2 from the sluggish blood, so venous O2 drops significantly
• Leads to an increased arterial-venous O2 difference (a-vO2 gradient)
• Causes:
  • Heart failure
  • Shock
  • Localized arterial obstruction (e.g., atherosclerosis)
  • Vasoconstriction (e.g., Raynaud's phenomenon)
  • Venous obstruction and edema (increases diffusion distance for O2)
  • Organs most vulnerable: kidneys, heart (during shock); liver and brain (during heart failure)

4. Histotoxic Hypoxia

• O2 delivery to tissues is adequate, but tissue cells cannot use the O2 supplied
• Venous blood actually has a high O2 tension (tissues don't extract it)
• Causes:
  • Cyanide poisoning - inhibits cytochrome oxidase in mitochondria, blocking oxidative phosphorylation and ATP production
  • Methylene blue and nitrites are used as treatment (they form methemoglobin, which binds cyanide to form the non-toxic cyanmethemoglobin)

SPECIAL SITUATIONS

Increased O2 Requirements

• If tissue O2 demand rises without a matching increase in blood flow, hypoxia develops
• Example: fever, thyrotoxicosis, exercise
• Skin is typically warm and flushed (not cyanosed) due to increased cutaneous blood flow

EFFECTS OF HYPOXIA

On Cells

• Hypoxia triggers production of Hypoxia-Inducible Factors (HIFs) - transcription factors made of α and β subunits
• In normal (oxygenated) tissues, α subunits are rapidly broken down
• In hypoxic cells, α-β dimers form and activate genes that produce:
  • Erythropoietin (stimulates red cell production)
  • Angiogenic factors (promote new blood vessel growth)

On the Brain (most sensitive organ)

• Brain is affected first in generalized hypoxia
• Sudden severe drop in inspired PO2 below 20 mmHg: loss of consciousness in 10-20 seconds, death in 4-5 minutes
• Milder hypoxia causes effects similar to alcohol:
  • Impaired judgment
  • Drowsiness
  • Dulled pain
  • Excitement
  • Disorientation
  • Loss of time sense
  • Headache
• Severe hypoxia: anorexia, nausea, vomiting, tachycardia, hypertension

On Breathing

• Hypoxia stimulates the carotid and aortic chemoreceptors and the respiratory center in the brainstem
• This increases ventilation (rate and depth of breathing), causing loss of CO2
• Can lead to respiratory alkalosis
• When CO2 falls too much alongside hypoxia, cerebrovascular resistance rises, cerebral blood flow falls, and brain hypoxia worsens

On the Heart and Circulation

• Generalized hypoxia causes systemic vasodilatation, increasing cardiac output
• In patients with heart disease, this demand can precipitate congestive heart failure
• In ischemic heart disease, low PaO2 can worsen myocardial ischemia

ADAPTATION TO CHRONIC HYPOXIA

• Increased hemoglobin concentration and red blood cell count (polycythemia) due to erythropoietin secretion
• Increased ventilation (chemoreceptor-driven)
• Increased cerebral blood flow (when CO2 is not excessively low)
• Chronic mountain sickness (at altitudes >4200 m): blunted respiratory drive, reduced ventilation, erythrocytosis, cyanosis, weakness, right ventricular enlargement (from pulmonary hypertension), and possible stupor

OXYGEN TREATMENT OF HYPOXIA

• O2 therapy 24 hrs/day for 2 years has been shown to significantly reduce mortality in chronic obstructive pulmonary disease (COPD)
• Hyperbaric oxygenation is useful in CO poisoning and cyanide poisoning

CYANOSIS (Sign of Hypoxia)

• A bluish discoloration of the skin and mucous membranes
• Caused by increased amounts of deoxygenated (reduced) hemoglobin in small blood vessels
• Most visible at: lips, nail beds, ears, cheekbones
• Detectable clinically when SaO2 falls to ~85% (may not be detected until 75% in dark-skinned individuals)
• Not present in: anemic hypoxia (not enough hemoglobin), histotoxic hypoxia, CO poisoning (produces a cherry-red flush instead)