Hypoxia Physiology

• Hypoxia is defined as a low level of oxygen in the body tissues.

Additional Terminology

• Hypoxemia is a low level of O2 in arterial blood.
• Hypercapnia is an increased partial pressure of CO2 in arterial blood.
• Hypocapnia is a decreased level of CO2 in ​​arterial blood.
• Hypoxia is often a pathological condition, but variations in arterial oxygen concentrations can be part of normal physiology.
• Hypoxia may be classified as generalized, affecting the whole body, or local, affecting a region of the body.
• Compensatory capacity is lower if hypoxia develops abruptly, lasts longer, and is severe.

Classification of Hypoxia by Onset

• Acute hypoxia has a rapid onset and lasts less than 6 hours.
• Chronic hypoxia lasts more than 90 days.
• Fulminant hypoxia is lightning-fast.
• Rapid onset is characteristic of acute hypoxia.
• Acute hypoxia is less frequent compared to chronic hypoxia.

Examples of Acute Hypoxia

• Mountain sickness
• Suffocation
• Airway obstruction with a foreign body
• Sudden suppression of the respiratory center
• Acute cardiac failure
• Shock, specifically acute circulatory failure

Characteristics of Chronic Hypoxia

• Chronic course.

Examples of Chronic Hypoxia

• Chronic heart failure/congestive heart failure
• Chronic respiratory failure
• Chronic anaemia

Characteristics of Fulminant Hypoxia

• Rare, Occurs mostly in catastrophe medicine.
• An explosive decompression of an airplane cabin at high altitude (10 km above sea level) is an example.
• Oxygen is forced out from the lungs due to the rapid expansion of gas during a rapid decompression
• Severe fatal barotrauma can result in rapid confusion, drowsiness, and death due to respiratory center failure.

Types of Hypoxia

• Hypoxic hypoxia
• Respiratory hypoxia
• Hemic hypoxia
• Circulatory hypoxia
• Histotoxic hypoxia

Hypoxic Hypoxia

• Oxygen pressure (SpO2) in the blood is too low to saturate the hemoglobin.
• Classification of hypoxic hypoxia is based on atmospheric pressure.
• Hypobaric hypoxic hypoxia is due to a low atmospheric pressure that induces altitude sickness.
• Normobaric hypoxic hypoxia is caused by staying in an inadequately ventilated room or a place with high CO2 levels.

Altitude Sickness

• Hypoxic symptoms are experienced by previously healthy mountain climbers.
• The pathogenesis involves hypobaric hypoxic hypoxia.
• Symptoms include headache, nausea, vomiting, dyspnea, and sleeping disorders.
• Typically begins at ~2500 m elevation
• At 3000 m elevation pulmonary oedema is possible due to constricted pulmonary arteries.
• At 3500 m elevation cerebral oedema may occur due to dilated cerebral arteries.
• High altitude euphoria is possible.
• Poor judgement of one's capacity
• Cerebral cortical inhibitory functions are diminished during hypoxia, is similar to alcohol intoxication
• Subsequently, severe depression and apathy can occur
• Reaching 5000–6000 m leads to deterioration in sensory, motor, and mental functions.
• Reduced awareness of the current situation, coordination difficulties, and decreased muscle function can occur at high altitudes.

Hypoxic Hypoxia Compensatory Mechanisms

• Hyperventilation occurs when air has a low level of CO2, it can lower hypoxia but cause hypocapnia (decreased level of CO2 in blood).
• Hypocapnia can lead to respiratory alkalosis (blood pH deviation to alkalinity).
• Hypocapnia lowers activity of the respiratory center.
• Hyperventilation occurs in circumstances when CO2 in the air is elevated.
• Circulatory response: The heart may beat faster to pump more blood to get more oxygen to the tissues.
• Secondary polycythemia: Over time, the body may produce more red blood cells to carry more oxygen.
• Hyperventilation in circumstances when CO2 in air is elevated.
• Can lower hypoxia but lead to hypercapnia (higher blood level of CO2)
• Hypercapnia can lead to respiratory acidosis (blood pH decreases).
• Circulatory response
• Secondary polycythemia

Respiratory Hypoxia

• Respiratory hypoxia is caused by a decline in respiratory functions at any level.
• This can be due to hypoventilation; impairment of gas diffusion via the alveolo-capillary membrane and ventilation-perfusion mismatch.
• Air doesn't reach all parts of the lungs or blood doesn't correctly through the lungs, leading to poor oxygen exchange.
• Respiratory hypoxia leads to Hypercapnia: elevated CO2 in blood, because CO2 cannot be exchanged via lungs.
• Hypercapnia can lead to respiratory acidosis (blood pH decreases).

Causes of Respiratory Hypoxia

• Airway obstruction: foreign body, tumor or inflammatory oedema (bronchitis), bronchospasms during bronchial asthma attack
• Paralysis of respiratory muscles.
• Skeletal deformations
• Respiratory center suppression (medications, narcotic abuse, hypocapnia)
• Superficial breathing due to pain relating to thoracic trauma, pleuritis, and intercostal neuralgia.
• Reduction of surface area for gas exchange: Lung emphysema damages to air sacs, which reduces the area for oxygen exchange.
• Decline of functioning alveoli: Pneumonia infection fills alveoli with fluid or pus, and lung oedema fluid buildup in lungs reduces oxygen absorption
• Pneumofibrosis: increased thickness of connective tissue in the alveolar septum: Cryptogenic fibrosing alveolitis causes lung scarring that thickens the walls of air sacs.
• Normal ventilation, no blood supply: increased "dead space".
• Pulmonary embolus.
• Lung emphysema (lots of enlarged alveoli with less surface area and fewer alveolar capillaries) enlarged air sacs with less blood supply
• Cardiovascular shock (blood flow to lungs is decreased).

Pulmonary Shunt

• Pulmonary shunt is the opposite of dead space.
• It consists of alveoli that are perfused but not ventilated.
• Pneumonia, pulmonary oedema.
• Tissue trauma – alveolar wall swelling.
• Atelectasis – collapse of alveoli from failure to expand.
• Mucous plugging.
• Pulmonary arteriovenous fistula.

Hemic Hypoxia

• Hemic hypoxia: lack of oxygen in the blood flowing to the tissues because of a decreased haemoglobin level.
• Anemia: low count of erythrocytes in blood leads to low hemoglobin levels.
• Functional hemoglobin defects: inability to transport oxygen molecules: CO intoxication or Fe oxidation from Fe2+ to Fe3+
• Methemoglobinemia; severe oxidative stress (smoking etc.).
• Increased hemoglobin affinity to oxygen: thalassemia, inherited hemoglobinopathies

Circulatory Hypoxia

• Oxygen can't be delivered to tissues because of poor blood circulation, even if there's enough oxygen in the lungs and blood.
• Decreased cardiac output leads to prolonged systemic transit time.
• The PaO2 in the blood can be initially normal. Even though blood oxygen (PaO2) may start off normal, tissues won't get enough oxygen because of sluggish blood flow.
• Cardiovascular failure
• Shock (any etiology).
• Circulatory hypoxia can rapidly progress to mixed hypoxia: circulatory + hemic; circulatory + respiratory hypoxia.
• Histotoxic hypoxia refers to a reduction in ATP production by the mitochondria due to a defect in the cellular usage of oxygen.
• Cyanide poisoning: cessation of aerobic cell metabolism.
• Cyanide binds to the enzyme cytochrome C oxidase and blocks the mitochondrial transport chain.
• Monobromides, and tetrachloromethane block Krebs cycle enzymes.
• Anesthetic substance overdose: dehydrogenase blockage.

Symptoms Of Hypoxia

• Cyanosis
• Dyspnea – subjective and objective difficulty of breathing
• Shortness of breath and breathlessness.
• Hypotension
• Fatigue
• Malaise
• Anxiety, confusion, insomnia
• Symptoms caused by compensatory mechanisms

Cyanosis

• Cyanosis is characterized by a blueish discoloration of the skin or mucous membranes.
• Central cyanosis occurs when the level of deoxygenated hemoglobin in the arteries is above 50 g/L with oxygen saturation below 85%.
• Types of cyanosis include central/ arterial cyanosis where arterial blood is not enough oxydated and contains reduced hemoglobin:
• Cyanosis might not be clinically evident in a patient with severe anemia due to inability to obtain a high enough level of reduced hemoglobin:
• Anemia means less hemoglobin overall:
• There's not enough hemoglobin in the blood to produce the high levels of reduced hemoglobin needed to cause cyanosis, even if oxygen levels are very low.
• Reduced hemoglobin is the key: Cyanosis becomes noticeable only when there's a high concentration of deoxygenated hemoglobin, which may not be possible in someone with very low total hemoglobin levels.

Features of Central Cyanosis

• Includes Tetralogy of Fallot congenital heart pathologies and lung diseases.
• Peripheral/ acral/ venous cyanosis is seen in the upper and lower extremities where the blood flow is less rapid.
• Examples of peripheral cyanosis are low cardiac output, venous stasis and exposure to extreme cold.
• The arterial blood gas shows the partial pressure of dissolved oxygen in the blood as well as the saturation of hemoglobin.
• The pulse oximeter measures the absorption of light at only two wavelengths which correspond to that of oxyhemoglobin and deoxyhemoglobin.
• There is Hypoxia without cyanosis if there is a due to anemia with total hemoglobin 60 – 90 g/L (normal level 120 – 150 g/L), CO intoxication: carboxyhemoglobin is lightly red and Histotoxic hypoxia.
• Target organs of hypoxia include: Brain, Heart, Lungs, Kidneys, Liver and Skeletal muscle.

Organs responsible for blood oxygenation and possible compensation

• Cardiovascular system
• Respiratory system
• Erythrocytes
• Tissue metabolism
• Compensatory mechanisms: Hyperventilation leads to hypoxic stimulation in an attempt to correct hypoxia at the expense of a CO2 loss
• Hyperventilation: leads to respiratory alkalosis and acts rapidly to compensate for respiratory acidosis.
• Tachycardia: Develops in hypoxic, respiratory, hemic hypoxia, increasing oxygen demand leading to myocardial hypoxic injury, result in circulatory hypoxia.

Compensatory Mechanisms

• In Centralization of blood circulation The body prioritizes sending blood to vital organs when faced with a shortage blood/oxygen.
• Renin-angiotensin-aldosterone system activation: Activated by hypovolemia.
• Positive effect, if hypoxia is due to blood loss.
• Have a negative impact in case of circulatory hypoxia if heart pathology is due to arterial hypertension.
• Increased erythropoietin synthesis in kidneys: increases RBC forms
• Secondary polycythemia increases the number of red blood cells.
• Positive effect, if hypoxia is due to blood loss.
• Negative effect: blood viscosity increases leading to elevated risk for thrombosis.
• The oxyhemoglobin dissociation curve describes the relationship between the saturation of hemoglobin and the partial pressure of arterial oxygen.
• Healthy adults, a PO₂ of ~27 mmHg corresponds to ~50% hemoglobin saturation which is known as the P50 of hemoglobin. There are stressors than can affect haemoglobin.

Rightward and Leftward Shift

• A rightward shift is caused by increased temperature, increased CO₂ production, causing decreased pH, increased 2,3-diphosphoglycerate, Hypoxia and Anaemia..
• A rightward shift is important when oxygen unload it is used to oxygen-starved tissues, sickle cell haemoglobin is unable to readily bind oxygen and right shifted.
• A leftward shift less PO2 can achieve a hemoglobin is high due to a high affinity in peripheral tissues.
• It is opposite to those creating right shifts.
• Is affected by: carbon monoxide oxygen-reducing spots and creates a shift, and fetal hemoglobin adapts for low pressures of oxygen in the uteroplacental circulation.