Causes Of Disease

Question 1

Who was the first Person who studied natural causes of disease scientifically?

Answer 1

Hippocrates

Question 2

When did the first Person who studied natural causes of disease scientifically?

Answer 2

400 BCE

Question 3

What is etiology?

Answer 3

Causes or initial events of disease

Question 4

What is pathology

Answer 4

The process of a disease.

Question 5

Is it more common for a disease to have a single cause or multiple?

Answer 5

Multiple

Question 6

Name a disease with a single cause.

Answer 6

Huntingtons

Question 7

Define Idiopathic.

Answer 7

Conditions with an unidentified cause.

Question 8

Sporadic conditions are…

Answer 8

…seemingly at random. Often used interchangeably with idiopathic but does not mean the same thing.

Question 9

How are the causes of disease classified?

Answer 9

Intrinsic/ genetic or extrinsic/enviromental

Question 10

Intrinsic causes often require?

Answer 10

Changes in an individuals genome. Typically can alter the function of a gene/ group of genes

Question 11

Name 4 ways in which an individuals genome can be changed.

Answer 11

Acronym : DINE
Changes include….
-Nuclear or mitochondrial changer to the genome
-Inherited mutations and other genetic variations(duplications, loss of genes, chromosomal abnormalities)
-De novo mutations (de novo - from new, occur while your alive)
-Epigenetic modifications - no change to the sequence but different expression .i.e. methylation and acetylation.

Question 12

How can the function of a gene/ group of genes be altered?

Answer 12

More/ less proteins
Same amount of proteins but more/less activity

Question 13

What are the 2 levels that the effects of genetic variations manifest at?

Answer 13

Cell autonomously
And
Non cell autonomously

Question 14

Explain what is meant by cell autonomous variations.

Answer 14

Cell X no longer expresses structural Protein Y so cell X is the wrong shape. It doesn’t have the protein but every cell has mutations

Question 15

Explain what is meant by non cell autonomous variability.

Answer 15

Cell X no longer secretes protein hormone Y, so cell Z can no longer function.
The cell that produces the hormone functions normally and the hormone should activate the next cell, but that second cell has been compromised functionally - so cell Z is the non-functional one

Question 16

Name all the different types of extrinsic causes.
Name the acronym first and build from there.

Answer 16

Acronym: NICELI
Injury
Infection
Nutrition and Diet
Lifestyle - smoking, exposure to workplace toxins
Chemical Poisoning - acute and chronic
Exposure to Radiation

Question 17

When the cause is not specifically intrinsic or extrinsic we call that?

Answer 17

Ambiguous/ or a grey area cause

Question 18

What are grey area causes often a result of?

Answer 18

A chain of events, like a cascade

Question 19

Give an example of a grey area cause of disease.

Answer 19

Allergies:
Intrinsic- genetically sensitive immune system
Extrinsic- Preceding allergen, trigggered by external stimuli
So defining intrinsic /extrinsic is dependent on viewpoint. Highly Subjective!

Question 20

Multiple cause diseases is not the most accurate term, what is the more accurate term?

Answer 20

Risk factor

Question 21

Is age a cause?

Answer 21

Age is often a contributing factor.
Usually as age increases the amount of TIME the individual with the intrinsic/extrinsic cause has been allowed to aggregate.

Question 22

Give an example of age being an intrinsic cause.

Answer 22

Biological Aging -> causes menopause ->triggered by decreased oestrogen production -> increases risk of Oestoporosis (more common in women)

Question 23

When is age an intrinsic cause?

Answer 23

When it describes the biological process of ageing.

Question 24

What type of diseases have a biological ageing cause?

Answer 24

Diseases associated with chronic inflammation.

Question 25

What are versions of intrinsic and extrinsic that are more reflective of that disease are called?

Answer 25

Genetic- intrinsic Environmental - extrinsic

Question 26

What are the risk factors for Parkinson’s disease?

Answer 26

1. Age 2. Genetics 3. Environment

Question 27

What are the four aspects of the molecular basis of disease with examples?

Answer 27

DIIC Cancer - Leukaemia, Lymphoma, Breast, Prostate Developmental diseases - Neural tube defects Inherited anaemia - sickle cell disease/ Beta-thalassaemia Inherited metabolic diseases - phenylketonuria

Question 28

List extrinsic causes of disease and state your mnemonic.

Answer 28

INCLInE Injury (Molecular basis of disease) Nutrition and diet Chemical poisoning Lifestyle - smoking, exposure to workplace toxins Infection Exposure to Radiation

Question 29

Which extrinsic cause of disease is classed under Microbiology and Immunology?

Answer 29

Infection

Question 30

Explain how nutrition and diet is an extrinsic cause of disease?

Answer 30

Nutritional -anaemias is a lack of vitamins and ions

Question 31

Explain the classification of developmental disorders.

Answer 31

Can be included in nutrition and diet. Having a lack of dietary folate and neural tube closure leads to developmental disorders. This is a mix of intrinsic and extrinsic and is caused by nutritional anaemia.

Question 32

What is the cause of Down’s syndrome?

Answer 32

Trigonometry of chromosome 21 which is inherited at conception and is therefore an intrinsic cause of disease.

Question 33

Cause of COVID-19. Intrinsic/extrinsic?

Answer 33

Infection caused by SARS-CoV-2 virus and hence is caused by an extrinsic cause.

Question 34

What causes of lung cancer are extrinsic?

Answer 34

Smoking tobacco Chemicals and workplace risks Air pollution Exposure to radon gas

Question 35

What causes of lung cancer are intrinsic?

Answer 35

Previous lung disease - but has its own causes like COPD Family history of lung cancer

Question 36

Broken tibia, Intrinsic/extrinsic?

Answer 36

Extrinsic. But the lecturer crashing his bike due to idiocy is a partially intrinsic cause

Question 37

What are the phases of cell cycle?

Answer 37

M - Mitosis G1 - Gap Phase 1 / cell growth S - DNA Synthesis G2 - Gap Phase 2 / More growth and preparation for mitosis

Question 38

What are mitogens?

Answer 38

A small bioactive protein or peptide that induces a cell to begin cell division, or enhances the rate of division by triggering mitosis. It does this primarily by relieving intracellular negative controls that otherwise block progress through the cell cycle.

Question 39

What factors control the cell cycle?

Answer 39

The cell cycle is controlled by many cell cycle control factors, namely cyclins, cyclin-dependent kinases (Cdks) and cyclin-dependent kinase inhibitors (CKIs). Cyclins and Cdks, which are positive regulators of the cell cycle, activate cell cycle factors that are essential for the start of the next cell cycle phase.

Question 40

What mechanisms underlie cell death?

Answer 40

Two major signaling pathways trigger apoptotic cell death: the mitochondrial (the intrinsic) pathway and the death receptor (the extrinsic) pathway.

Question 41

Explain the intrinsic pathway that underlies the death receptor.

Answer 41

The intrinsic pathway is regulated by intracellular signals, often in response to cellular stress such as DNA damage, oxidative stress, or growth factor withdrawal. The central regulators of this pathway are members of the B-cell lymphoma 2 (Bcl-2) family, which includes both pro-apoptotic (e.g., Bax, Bak, Bad) and anti-apoptotic (e.g., Bcl-2, Bcl-XL) proteins. Various stimuli can lead to the activation of pro-apoptotic Bcl-2 family members, resulting in mitochondrial outer membrane permeabilization (MOMP). This allows the release of pro-apoptotic proteins, including cytochrome c, from the mitochondria into the cytoplasm. Cytochrome c, together with apoptotic protease activating factor 1 (Apaf-1) and ATP, forms the apoptosome, which recruits and activates procaspase-9. Activated caspase-9 then cleaves and activates downstream effector caspases, such as caspase-3, -6, and -7. Additionally, tBID generated from the extrinsic pathway can also trigger MOMP, amplifying the apoptotic signal through the intrinsic pathway.

Question 42

Explain the extrinsic cell apoptosis signalling pathway?

Answer 42

The extrinsic pathway is initiated by external signals such as death ligands binding to death receptors on the cell surface. Prominent death ligand-receptor pairs include Fas ligand (FasL) binding to Fas receptor (Fas), TNF-α binding to TNF receptor 1 (TNFR1), and TRAIL binding to death receptors DR4 and DR5. Ligand binding induces receptor trimerization, leading to the recruitment of adaptor proteins such as FADD (Fas-associated death domain) or TRADD (TNFR1-associated death domain). These adaptors then recruit procaspase-8, forming the death-inducing signaling complex (DISC). Procaspase-8 within the DISC is activated by proximity-induced self-cleavage, forming active caspase-8. Caspase-8 then initiates the apoptotic cascade by directly activating effector caspases (e.g., caspase-3, -6, and -7) or by cleaving BH3 interacting-domain death agonist (BID) to generate truncated BID (tBID), which activates the intrinsic pathway.

Question 43

Explain the cell apoptosis execution phase?

Answer 43

Once initiated by either the extrinsic or intrinsic pathway, the execution phase of apoptosis involves the activation of effector caspases, which cleave various cellular substrates, leading to the characteristic morphological and biochemical changes associated with apoptosis, including chromatin condensation, DNA fragmentation, membrane blebbing, and formation of apoptotic bodies. Effector caspases also cleave inhibitor of caspase-activated DNase (ICAD), allowing caspase-activated DNase (CAD) to enter the nucleus and degrade chromosomal DNA. These signaling pathways are tightly regulated to ensure proper execution of apoptosis, with dysregulation often contributing to various diseases, including cancer, neurodegenerative disorders, and autoimmune diseases.