Causes of Disease

Question 1

What does aetiology mean?

Answer 1

• The cause, set of causes, or manner of causation of a disease or condition.
• The causation of diseases and disorders as a subject of investigation.
• The investigation or attribution of the cause or reason for something, often expressed in terms of historical or mythical explanation.

Question 2

Causes of disease are usually categorised in what 2 parts?

Answer 2

intrinsic (from within) and extrinsic (from outside)

Question 3

Intrinsic causes

Answer 3

•  = Changes in an individual’s genome
– Nuclear or mitochondrial 
– Inherited mutations and other genetic variations
– de novo mutations
– Epigenetic modifications 

• Typically alter the function of a gene (or group of genes)
– E.g. more/less protein or same amount but more/less activity

• Effects of genetic variations can manifest at a variety of levels
– Cell autonomously
– Cell non-autonomously
Cell X no longer expresses structural protein Y, so
cell X is the wrong shape
Cell X no longer secretes protein hormone Y, so cell Z no longer functions

Question 4

Extrinsic causes

Answer 4

• Numerous!
– Injury
– Infection
– Nutrition and diet
– Lifestyle, e.g. smoking, exposure to workplace toxins
– Chemical poisoning (acute and chronic)
– Exposure to radiation

Question 5

Grey areas

Answer 5

• The terms intrinsic or extrinsic can be ambiguous
• Causes of disease are often a chain of events
– Are allergies caused by a sensitive immune system (intrinsic) or the preceding allergen (extrinsic)?
• Intrinsic or extrinsic depends on viewpoint, i.e. extrinsic to what: cell, tissue, organ, body?
– Pay attention to the context!

Question 6

Age as a cause of disease pt 1

Answer 6

• Age is a contributing factor to many diseases, but is it a cause?
• Age really just means ‘time’, in the context of causes that accumulate, e.g.

(exponential graph - showing number of mutations (cartilage damage) and osteoarthritis risk/cancer risk)

Question 7

Age as a cause of disease pt 2

Answer 7

Age can be an intrinsic cause when it describes the biological process of aging.

e.g. Risk of osteoporosis

Question 8

Alternative Descriptions

Answer 8

• For many diseases, causes are grouped as “genetic” and “environmental”

• These terms are versions of intrinsic and extrinsic that
are more reflective of that disease
– E.g. Parkinson’s disease risk factors are:
1. Age, 2. genetics and 3. environment

genetics= inherited gene variants 
environment = exposure to pesticides, herbicides, solvents and other environmental toxins

Question 9

Intrinsic examples

Answer 9

Many (i.e. Molecular Basis of Disease)
– Cancer (inc. Leukaemia, Lymphoma, Myeloma, Breast, Prostate)
– Developmental diseases (e.g. Neural tube defects)
– Inherited anaemia (e.g. Sickle cell disease, β-thalassaemia)
– Inherited metabolic diseases (e.g. phenylketonuria)

Question 10

Extrinsic examples

Answer 10

• List of causes:
NO
– Injury ( no - this is MOLECULAR basis of disease)
– Infection (no -Microbiology and Immunology Module, but diseases where the immune system is a cause are covered, e.g. Type I diabetes, autoimmune anaemia)

YES
– Nutrition and diet (yes, e.g. Nutritional anaemias. Developmental disorders, e.g. lack of dietary folate and neural tube closure)

YES, LOTS
– Lifestyle, e.g. smoking, exposure to workplace toxins
– Chemical poisoning (acute and chronic)
– Exposure to radiation

Question 11

Intrinsic or extrinsic

Answer 11

• Cause of Down Syndrome
– Trisomy of chromosome 21, inherited at conception
– Intrinsic

• Cause of COVID-19
– Infection with SARS-CoV-2
– Extrinsic

• Causes of lung cancer (from Cancer Research UK)

• Extrinsic: smoking tobacco, chemicals and workplace risks, air pollution, exposure to radon gas
• Intrinsic(but with its own causes): previous lung disease, family history of lung cancer

• Dan’s broken tibia
- Extrinsic (although I crashed my bike because I’m an idiot, so partly intrinsic too)