Hyperpyrexia, Pyrogen, Orthopnea, and Eupnea

Hyperpyrexia is defined as an extremely high fever.
In humans, it typically refers to a fever with a temperature greater than or equal to 41.5 °C (106.7 °F).
Such extreme elevations in body temperature are considered medical emergencies.
Rapid cooling measures are usually required to prevent potential neurological damage and other serious complications.
Causes of hyperpyrexia can include severe infections, certain medications, and heatstroke.
Infections that may lead to marked temperature elevations include, but are not limited to: pneumonia, sepsis, and overwhelming viral illnesses.
Certain central nervous system (CNS) disorders can also manifest with hyperpyrexia
Drug-induced hyperpyrexia can occur as an adverse reaction to some medications, including anesthetics and neuroleptics.
Malignant hyperthermia is an example of genetic susceptibility leading to hyperpyrexia in the presence of certain anaesthetic agents.
Hyperpyrexia warrants immediate medical assessment to identify the underlying cause and initiate appropriate management

A pyrogen is a substance that produces fever.
Pyrogens can be either internal (endogenous) or external (exogenous) to the body. Endogenous pyrogens are cytokines produced by the body's immune cells in response to infection, inflammation, or trauma.
Exogenous pyrogens are substances originating outside the body that can induce fever.
Exogenous pyrogens include bacteria, viruses, fungi, and their toxins.
The most well-known exogenous pyrogens are lipopolysaccharides (LPS), which are components of the cell walls of Gram-negative bacteria.
Pyrogens trigger the release of endogenous pyrogens, such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α).
These endogenous pyrogens act on the hypothalamus, the region of the brain that regulates body temperature.
Within the hypothalamus, pyrogens stimulate the production of prostaglandin E2 (PGE2).
PGE2 resets the body's thermostat to a higher temperature, leading to fever.
Fever is a natural defense mechanism that enhances immune function and inhibits the growth of some pathogens.
However, excessively high or prolonged fever can be detrimental and require medical intervention.

Orthopnea is defined as shortness of breath (dyspnea) that occurs when lying flat.
It is typically relieved by sitting up or standing.
Orthopnea is a common symptom of left ventricular heart failure.
In left ventricular heart failure, the heart is unable to effectively pump blood, leading to increased pressure in the pulmonary veins.
When a person lies flat, blood is redistributed from the lower extremities and abdomen to the central circulation, increasing venous return to the heart.
In a healthy individual, the heart can accommodate this increased volume without difficulty.
However, in someone with left ventricular heart failure, the compromised heart cannot effectively pump the additional blood.
This leads to further elevation of pulmonary venous pressure and fluid transudation into the lung interstitium.
The resulting pulmonary congestion causes shortness of breath.
Patients with orthopnea often use multiple pillows to prop themselves up at night, a practice known as "sleeping in the orthopneic position."
Other causes of orthopnea include:
- Bilateral diaphragmatic paralysis
- Severe obesity
- Ascites
Orthopnea should be distinguished from paroxysmal nocturnal dyspnea (PND).
PND is sudden, severe shortness of breath that awakens a person from sleep.
While both orthopnea and PND are associated with heart failure, PND typically occurs several hours after lying down and is more abrupt in onset.

Eupnea is normal, good, unlabored breathing, sometimes also known as quiet breathing or resting respiratory rate.
In eupnea, respiration occurs automatically without conscious effort.
The rate, depth, and rhythm of breathing are within normal limits.
The normal respiratory rate for adults is typically between 12 and 20 breaths per minute.
Eupnea is regulated by the respiratory center in the brainstem, which controls the muscles of respiration (diaphragm and intercostals).
The respiratory center receives input from various sources, including:
- Chemoreceptors that monitor blood levels of oxygen, carbon dioxide, and pH.
- Mechanoreceptors in the lungs and airways that detect lung stretch and irritants.
- The cerebral cortex, which allows for voluntary control of breathing.
During eupnea, tidal volume (the amount of air inhaled or exhaled with each breath) is typically around 500 mL.
The inspiratory and expiratory phases of eupnea are typically smooth and effortless.
Eupnea is disrupted in various respiratory disorders, such as asthma, pneumonia, and chronic obstructive pulmonary disease (COPD).
Deviations from eupnea, such as dyspnea (shortness of breath), tachypnea (rapid breathing), and bradypnea (slow breathing), can indicate underlying medical conditions.

Podcast