Cause, also known as etiology () and aetiology, is the

reason Reason is the capacity of consciously applying logic by drawing valid conclusions from new or existing information, with the aim of seeking the truth. It is associated with such characteristically human activities as philosophy, religion, scien ...

or origination of something. The word ''

etiology Etiology (; alternatively spelled aetiology or ætiology) is the study of causation or origination. The word is derived from the Greek word ''()'', meaning "giving a reason for" (). More completely, etiology is the study of the causes, origins ...

'' is derived from the

Greek Greek may refer to: Anything of, from, or related to Greece, a country in Southern Europe: *Greeks, an ethnic group *Greek language, a branch of the Indo-European language family **Proto-Greek language, the assumed last common ancestor of all kno ...

, ''aitiologia'', "giving a reason for" (, ''aitia'', "cause"; and , ''

-logia ''-logy'' is a suffix in the English language, used with words originally adapted from Ancient Greek ending in ('). The earliest English examples were anglicizations of the French '' -logie'', which was in turn inherited from the Latin '' -lo ...

'').

Description

In medicine,

refers to the cause or causes of

disease A disease is a particular abnormal condition that adversely affects the structure or function (biology), function of all or part of an organism and is not immediately due to any external injury. Diseases are often known to be medical condi ...

s or pathologies. Where no etiology can be ascertained, the disorder is said to be

idiopathic An idiopathic disease is any disease with an unknown cause or mechanism of apparent spontaneous origin. For some medical conditions, one or more causes are somewhat understood, but in a certain percentage of people with the condition, the cause ...

. Traditional accounts of the causes of disease may point to the "

evil eye The evil eye is a supernatural belief in a curse brought about by a malevolent glaring, glare, usually inspired by envy. Amulets to Apotropaic, protect against it have been found dating to around 5,000 years ago. It is found in many cultures i ...

". The

Ancient Roman In modern historiography, ancient Rome is the Roman people, Roman civilisation from the founding of Rome, founding of the Italian city of Rome in the 8th century BC to the Fall of the Western Roman Empire, collapse of the Western Roman Em ...

scholar

Marcus Terentius Varro Marcus Terentius Varro (116–27 BCE) was a Roman polymath and a prolific author. He is regarded as ancient Rome's greatest scholar, and was described by Petrarch as "the third great light of Rome" (after Virgil and Cicero). He is sometimes call ...

put forward early ideas about

microorganism A microorganism, or microbe, is an organism of microscopic scale, microscopic size, which may exist in its unicellular organism, single-celled form or as a Colony (biology)#Microbial colonies, colony of cells. The possible existence of unseen ...

s in a 1st-century BC book titled ''On Agriculture''. Medieval thinking on the etiology of disease showed the influence of

Galen Aelius Galenus or Claudius Galenus (; September 129 – AD), often Anglicization, anglicized as Galen () or Galen of Pergamon, was a Ancient Rome, Roman and Greeks, Greek physician, surgeon, and Philosophy, philosopher. Considered to be one o ...

and of

Hippocrates Hippocrates of Kos (; ; ), also known as Hippocrates II, was a Greek physician and philosopher of the Classical Greece, classical period who is considered one of the most outstanding figures in the history of medicine. He is traditionally referr ...

. Medieval

Europe Europe is a continent located entirely in the Northern Hemisphere and mostly in the Eastern Hemisphere. It is bordered by the Arctic Ocean to the north, the Atlantic Ocean to the west, the Mediterranean Sea to the south, and Asia to the east ...

an doctors generally held the view that disease was related to the air and adopted a miasmatic approach to disease etiology. Etiological discovery in medicine has a history in

Robert Koch Heinrich Hermann Robert Koch ( ; ; 11 December 1843 – 27 May 1910) was a German physician and microbiologist. As the discoverer of the specific causative agents of deadly infectious diseases including tuberculosis, cholera and anthrax, he i ...

's demonstration that species of the

pathogenic bacteria Pathogenic bacteria are bacteria that can cause disease. This article focuses on the bacteria that are pathogenic to humans. Most species of bacteria are harmless and many are Probiotic, beneficial but others can cause infectious diseases. The nu ...

Mycobacterium tuberculosis ''Mycobacterium tuberculosis'' (M. tb), also known as Koch's bacillus, is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, ''M. tuberculosis'' ha ...

'' causes the disease

tuberculosis Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can al ...

; ''

Bacillus anthracis ''Bacillus anthracis'' is a gram-positive and rod-shaped bacterium that causes anthrax, a deadly disease to livestock and, occasionally, to humans. It is the only permanent (obligate) pathogen within the genus ''Bacillus''. Its infection is a ty ...

'' causes

anthrax Anthrax is an infection caused by the bacterium '' Bacillus anthracis'' or ''Bacillus cereus'' biovar ''anthracis''. Infection typically occurs by contact with the skin, inhalation, or intestinal absorption. Symptom onset occurs between one ...

, and ''

Vibrio cholerae ''Vibrio cholerae'' is a species of Gram-negative bacteria, Gram-negative, Facultative anaerobic organism, facultative anaerobe and Vibrio, comma-shaped bacteria. The bacteria naturally live in Brackish water, brackish or saltwater where they att ...

'' causes

cholera Cholera () is an infection of the small intestine by some Strain (biology), strains of the Bacteria, bacterium ''Vibrio cholerae''. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea last ...

. This line of thinking and evidence is summarized in

Koch's postulates Koch's postulates ( ) are four criteria designed to establish a causality, causal relationship between a microbe and a disease. The postulates were formulated by Robert Koch and Friedrich Loeffler in 1884, based on earlier concepts described by ...

. But proof of causation in infectious diseases is limited to individual cases that provide experimental evidence of etiology. In

epidemiology Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and Risk factor (epidemiology), determinants of health and disease conditions in a defined population, and application of this knowledge to prevent dise ...

, several lines of evidence together are required to for

causal inference Causal inference is the process of determining the independent, actual effect of a particular phenomenon that is a component of a larger system. The main difference between causal inference and inference of association is that causal inference an ...

. Austin Bradford Hill demonstrated a causal relationship between

tobacco smoking Tobacco smoking is the practice of burning tobacco and ingesting the resulting smoke. The smoke may be inhaled, as is done with cigarettes, or released from the mouth, as is generally done with pipes and cigars. The practice is believed to hav ...

and

lung cancer Lung cancer, also known as lung carcinoma, is a malignant tumor that begins in the lung. Lung cancer is caused by genetic damage to the DNA of cells in the airways, often caused by cigarette smoking or inhaling damaging chemicals. Damaged ...

, and summarized the line of reasoning in the

Bradford Hill criteria The Bradford Hill criteria, otherwise known as Hill's criteria for causation, are a group of nine principles that can be useful in establishing epidemiologic evidence of a causal relationship between a presumed cause and an observed effect and ha ...

, a group of nine principles to establish epidemiological causation. This idea of causality was later used in a proposal for a ''Unified concept of causation''.

Disease causative agent

The infectious diseases are caused by infectious agents or

pathogens In biology, a pathogen (, "suffering", "passion" and , "producer of"), in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ. The term ...

. The infectious agents that cause disease fall into five groups: viruses, bacteria, fungi, protozoa, and helminths (worms). The term can also refer to a toxin or toxic chemical that causes illness.

Chain of causation and correlation

Further thinking in epidemiology was required to distinguish causation from association or statistical correlation. Events may occur together simply due to chance,

bias Bias is a disproportionate weight ''in favor of'' or ''against'' an idea or thing, usually in a way that is inaccurate, closed-minded, prejudicial, or unfair. Biases can be innate or learned. People may develop biases for or against an individ ...

confounding In causal inference, a confounder is a variable that influences both the dependent variable and independent variable, causing a spurious association. Confounding is a causal concept, and as such, cannot be described in terms of correlatio ...

, instead of one event being caused by the other. It is also important to know which event is the cause. Careful sampling and measurement are more important than sophisticated statistical analysis to determine causation. Experimental evidence involving interventions (providing or removing the supposed cause) gives the most compelling evidence of etiology. Related to this, sometimes several symptoms always appear together, or more often than what could be expected, though it is known that one cannot cause the other. These situations are called

syndrome A syndrome is a set of medical signs and symptoms which are correlated with each other and often associated with a particular disease or disorder. The word derives from the Greek language, Greek σύνδρομον, meaning "concurrence". When a sy ...

s, and normally it is assumed that an underlying condition must exist that explains all the symptoms. Other times there is not a single cause for a disease, but instead a chain of causation from an initial trigger to the development of the clinical disease. An etiological agent of disease may require an independent co-factor, and be subject to a promoter (increases expression) to cause disease. An example of all the above, which was recognized late, is that

peptic ulcer disease Peptic ulcer disease is when the inner part of the stomach's gastric mucosa (lining of the stomach), the first part of the small intestine, or sometimes the lower esophagus, gets damaged. An ulcer in the stomach is called a gastric ulcer, while ...

may be induced by stress, requires the presence of acid secretion in the stomach, and has primary etiology in ''

Helicobacter pylori ''Helicobacter pylori'', previously known as ''Campylobacter pylori'', is a gram-negative, Flagellum#bacterial, flagellated, Bacterial cellular morphologies#Helical, helical bacterium. Mutants can have a rod or curved rod shape that exhibits l ...

'' infection. Many chronic diseases of unknown cause may be studied in this framework to explain multiple epidemiological associations or

risk factor In epidemiology, a risk factor or determinant is a variable associated with an increased risk of disease or infection. Due to a lack of harmonization across disciplines, determinant, in its more widely accepted scientific meaning, is often use ...

s which may or may not be causally related, and to seek the actual etiology.

Etiological heterogeneity

Some diseases, such as

diabetes Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...

hepatitis Hepatitis is inflammation of the liver parenchyma, liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), Anorexia (symptom), poor appetite ...

, are syndromically defined by their

signs and symptoms Signs and symptoms are diagnostic indications of an illness, injury, or condition. Signs are objective and externally observable; symptoms are a person's reported subjective experiences. A sign for example may be a higher or lower temperature ...

, but include different conditions with different etiologies. These are called heterogeneous conditions. Conversely, a single etiology, such as

Epstein–Barr virus The Epstein–Barr virus (EBV), also known as human herpesvirus 4 (HHV-4), is one of the nine known Herpesviridae#Human herpesvirus types, human herpesvirus types in the Herpesviridae, herpes family, and is one of the most common viruses in ...

, may in different circumstances produce different diseases such as

mononucleosis Infectious mononucleosis (IM, mono), also known as glandular fever, is an infection usually caused by the Epstein–Barr virus (EBV). Most people are infected by the virus as children, when the disease produces few or no symptoms. In young adu ...

nasopharyngeal carcinoma Nasopharyngeal carcinoma (NPC), or nasopharynx cancer, is the most common cancer originating in the nasopharynx, most commonly in the postero-lateral nasopharynx or pharyngeal recess (fossa of Rosenmüller), accounting for 50% of cases. NPC occurs ...

, or

Burkitt's lymphoma Burkitt's lymphoma is a cancer of the lymphatic system, particularly B lymphocytes found in the germinal center. It is named after Denis Parsons Burkitt, the Irish surgeon who first described the disease in 1958 while working in equatorial Africa ...

Endotype

An endotype is a subtype of a condition, which is defined by a distinct functional or pathobiological mechanism. This is distinct from a

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological propert ...

, which is any observable characteristic or trait of a

, such as

morphology Morphology, from the Greek and meaning "study of shape", may refer to: Disciplines *Morphology (archaeology), study of the shapes or forms of artifacts *Morphology (astronomy), study of the shape of astronomical objects such as nebulae, galaxies, ...

, development, biochemical or physiological properties, or behavior, without any implication of a mechanism. It is envisaged that

patient A patient is any recipient of health care services that are performed by Health professional, healthcare professionals. The patient is most often Disease, ill or Major trauma, injured and in need of therapy, treatment by a physician, nurse, op ...

s with a specific endotype present themselves within phenotypic clusters of diseases. One example is asthma, which is considered to be a

, consisting of a series of endotypes. This is related to the concept of

disease entity A disease is a particular abnormal condition that adversely affects the structure or function of all or part of an organism and is not immediately due to any external injury. Diseases are often known to be medical conditions that are asso ...

. Other example could be

AIDS The HIV, human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a Preventive healthcare, pr ...

, where an HIV infection can produce several clinical stages. AIDS is defined as the clinical stage IV of the HIV infection.

References

External links

* {{Authority control Pathology Epidemiology