Cell injury and apoptosis

Question 1

How would you identify/diagnose a disease in an individual?

Answer 1

1. Clinical history to document symptoms
2. Examine the patient for clinic signs
3. Performing investigations

Question 2

What is diagnostic laboratory test

Answer 2

• A sample from a patient and the result help to allocate the case to a diagnostic group. Depending on the sample it is then either:
  1. Quantitative measurement: interpreted in relationship to a “normal” range of values
  2. Subjective assessment: based on the assessment of a pathologist

Question 3

What is Epidemiological approach?

Answer 3

• The study of disease in POPULATIONS and the distribution of diseases in relation to place and time

Question 4

What does the Epidemiological approach identify and involve?

Answer 4

• Identification of the possible causes and modes of acquisition of disease
• Involves recording and analysis of data about a disease in groups of people rather than in an individual alone

Question 5

What does the Epidemiology establish?

Answer 5

the ASSOCIATION between risk factor and the occurrence of a disease but NOT the CASUAL RELATIONSHIP

Question 6

What are the 3 types of Epidemiological studies?

Answer 6

• Prospective studies
• Retrospective studies
• Cross-sectional studies

Question 7

What is Prospective studies? (Epidemiological studies)

Answer 7

• Subjects followed over time (e.g. non smokers and smoker people will be followed for 20 years to see if smoking causes lung cancer)
• Risk factors monitored ( see if more smokers causes lung cancer than non smokers)
• Relative risk determined (probability of smoking causing that disease)

Question 8

What is Retrospective studies? (Epidemiological studies)

Answer 8

• Looking backward over a period of time (ask patient to recall their pass history. Relying on this recall is not as reliable, and you can not measure anything as it is based on past memory)
• Past exposure to suspected aetiological factors examined
• Odds ratio determined (there is no true probability.)

Question 9

What is Cross-sectional studies? (Epidemiological studies)

Answer 9

• Prevalence between different population at a particular time
• Mainly for public health planning
• Assess the association between risk factors and a disease, but limited

Question 10

Why are Autopsies preformed?

Answer 10

• May be performed for legal or medical purpose
• Information can be used for clinical audit, education, medical research
• Diagnostic discrepancies are revealed by autopsies in ~30% of cases

Question 11

Name 2 different Autopsies

Answer 11

• Medicolegal autopsies
• Clinical autopsies

Question 12

What is Medicolegal autopsies?

Answer 12

• To determine the cause of death
• To collect evidence that may be used in the prosecution of those alleged to be responsible for the death
• To be performed by STATE FORENSIC PATHOLOGISTS

Question 13

What is Clinical autopsies (non medicolegal)?

Answer 13

• On patients who die in hospital with unclear diagnosis or other reasons, but very useful information can be gathered from autopsies

Question 14

Normal cells A_____ in response to challenges to meet new demands

Answer 14

Adapts

Question 15

What is Cell injury

Answer 15

• If challenge is too great, or for too long, cells fail to meet this demand and show signs of injury: change or loss of function; change of morphology
• Cell injury can either be REVERSIBLE or IRREVERSIBLE

Question 16

What happens when Cell injury is irreversible?

Answer 16

• Irreversibly injured cells undergo further morphologic changes, recognized as cell death
  1. Necrosis
  2. Apoptosis

Question 17

What happens in Reversible Cell injury?

Answer 17

• If injury occurs it is usually reversible
• The insult has to be removed very quickly and the cell can then recover

Question 18

What happens in Irreversible cell injury?

Answer 18

• If the insult still exist, and develops to be even greater, it can lead to cell death

Question 19

Name some causes of cell injury

Answer 19

• Oxygen deprivation: Hypoxia; Ischemia
• Physical agents: Mechanical trauma; Extreme temperature
• Chemical agents and Drugs: Cyanide; CO; Alcohol
• Infectious agents: Viruses; Bacteria;
  -Immunologic reactions: Anaphylactic reaction to a protein
• Nutritional imbalances: Deficiencies of specific vitamins; Undernutrition and overnutrition
• Genetic derangements: Sickle cell anaemia

Question 20

Mechanisms of cell injury is complex and unknown in many cases, what are the principles in the study of cell injury?

Answer 20

• Cellular response to stimuli - depends on the type, severity and duration of injury
• Consequences of injury - depends on the type, state and adaptability of injured cells
• Cell injury results from - functional and biochemical abnormalities in one or several of essential cellular components

Question 21

What are FREE RADICALS?

Answer 21

• Are chemical species with a single unpaired electron in the outer orbit e.g. O2-
• Therefore chemically very active, and these molecules can react with a lot of other molcules

Question 22

Name mechanisms where ROS is generated (within cells)

Answer 22

• Absorption of radiant energy: ultraviolet light, x-rays
• Reduction-oxidation reactions
• Transition metals donate or accept free electrons during intracellular reactions: H2O2 + Fe3+ -> Fe3+ + OH + OH-
• Nitric oxide (ONOO-)

Question 23

What induced cell injury is caused to to ROS?

Answer 23

• Lipid peroxidation of membranes - oxidative damage is initiated when the double bonds in unsaturated fatty acids of membrane lipids are attacked by oxygen-derived free radicals
• Oxidative modification of proteins - oxidation of amino acid residue side chains, formation of protein-protein cross-linkages (e.g. disulphide bonds), and oxidation of the protein backbone, resulting in protein fragmentation
• DNA damage - Reactions with thymine in nuclear and mitochondrial DNA produce single-stranded breaks in DNA