1- Causes of disease: overview

Question 1

What is etiology?

Answer 1

• cause or causes of disease

- first studied by Hippocrates

Question 2

What are idiopathic diseases?

Answer 2

Conditions with no known cause

Question 3

What is sporadic?

Answer 3

Diseases that occur at random with no obvious patterns- i.e. at random, irregular intervals

Question 4

How can causes of disease be classified?

Answer 4

• intrinsic= from within body

- extrinsic= from outside body

Question 5

Name extrinsic causes of disease

Answer 5

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

Question 6

Name intrinsic causes of disease

Answer 6

=Changes in an individual’s genome

• Nuclear or mitochondrial
• Inherited mutations and other genetic variations
• de novo mutations
• Epigenetic modifications- chemical DNA methylation, phosphorylation, acetylation of histones, no change to DNA sequence but behaviour of DNA changed, and expression of genes changed

Question 7

Intrinsic causes- What do changes to genome lead to?

Answer 7

Typically alter the function of a gene (or group of genes)

E.g. more/less protein or same amount but more/less activity

Question 8

Intrinsic causes- At what levels can the effects of genetic variations manifest?

Answer 8

-Cell autonomously
Cell X no longer expresses structural protein Y, so cell X is the wrong shape.
-Cell non-autonomously
Cell X no longer secretes protein hormone Y, so cell Z no longer functions.

Question 9

State the 3 grey areas.

Answer 9

1. Terms intrinsic or extrinsic can be ambiguous
2. Causes of disease are often a chain of events. eg. Are allergies caused by a sensitive immune system (intrinsic) or the preceding allergen (extrinsic)?
3. Intrinsic or extrinsic depends on viewpoint, i.e. extrinsic to what: cell, tissue, organ, body?

Question 10

Age is a contributing factor to many diseases, but is it a cause?

Answer 10

Age is a synonym ‘time’, in the context of causes that accumulate, e.g. number of mutations accumulating= accumulated cancer risk overtime

Question 11

When is age an intrinsic cause?

Answer 11

When it describes biological process of ageing
ageing - menopause - decreased oestrogen - risk of osteoporosis
-Many diseases associated with chronic inflammation also have a biological ageing as a cause

Question 12

What are the alternative descriptions of causes of disease?

Answer 12

Genetic and environmental

These terms are versions of intrinsic and extrinsic that are more reflective of that disease

Question 13

What diseases have intrinsic causes?

Answer 13

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 14

What is the cause of Down Syndrome?

Answer 14

• Trisomy of chromosome 21, inherited at conception

- Intrinsic

Question 15

What is the cause of COVID-19?

Answer 15

Infection with SARS-CoV-2

Extrinsic

Question 16

What are the causes of lung cancer?

Answer 16

Extrinsic
-smoking tobacco 
-chemicals and workplace risks
-air pollution
-exposure to radon gas
Intrinsic 
-previous lung disease
-family history of lung cancer

Question 17

What are the phases of cell cycle?

Answer 17

G1phase,
Sphase(synthesis)
G2phase
Mphase(mitosisand cytokinesis)

Question 18

Describe mitosis?

Answer 18

Prophase: chromosomes condense, centrosomes move to opposite poles, mitotic spindle forms
Prometaphase: breakdown of nuclear envelope, chromosomes attach to mitotic spindle via the kinetochore
metaphase: centrosome are at opposite poles, chromosome are at their most condensed and line up at the equator of the mitotic spindle
anaphase: sister chromatids separate synchronously, each new daughter chromosome moving to the opposite spindle pole
telophase: chromosome arrives at the spindle poles, chromosomes decondense, nuclear envelope reforms
cytokinesis: cytoplasm divides, at the position of the metaphase plane, contractile ring of actin and myosin II constrict the cell into two new cells

Question 19

What are mitogens?

Answer 19

A mitogen is a peptide or small protein that induces a cell to begin cell division: mitosis.

Question 20

What factors control the cell cycle?

Answer 20

Positive regulators= cyclins and cyclin-dependent kinases (Cdk)
Cdk bound to cyclin- active- phosphorylate target protein
Cdk activation triggers the next step in the cell cycle such as entry into S phase, M phase
Cyclin degradation terminates Cdk activity

Question 21

What mechanisms underlie cell death?

Answer 21

Intrinsic- mitochondrial pathway, mediated by noxious stimuli that lead to mitochondrial injury
Extrinsic- death receptor pathway, mediated by activation of death receptors and BCL-2 regulated