Cell injury, apoptosis and death

Question 1

Steps taken to diagnose a patient

Answer 1

Observe medical history. Examine signs and symptoms. Obtain clinical tests and investigations including scans

Question 2

Quantitative diagnostic measurement

Answer 2

Measure a sample from the patient to see whether or not it is within the normal range of values e.g. ELISA

Question 3

Subjective for diagnostic assessment

Answer 3

Based on the assessment of a pathologist to see whether something is pathological or not e.g. microscopy

Question 4

Epidemiological diagnostic approach

Answer 4

Recording and analysing data of a specific disease in groups of people rather than an individual to give indication as to how the disease spreads in order to prepare introduce public health prevention measures

Question 5

Aims of epidemiological studies

Answer 5

To provide aetiological clues (risk factors rather than actual cause), planned preventative measures, provide adequate medical facilities and population screening for early diagnosis

Question 6

Basic approaches to conduct epidemiological studies

Answer 6

Prospective studies, retrospective studies and cross-sectional studies

Question 7

Prospective studies

Answer 7

Subjects are followed longitudinally, risk factors monitored and a relative risk is determined. Measures the incidence of death and those exposed as well as those on exposed to the risk factor

Question 8

Quantitative system that determines indicates risk factor

Answer 8

No risk = 1

More likely to cause risk = <1

Less likely to cause risk = >1

Question 9

Retrospective studies

Answer 9

Looks at past exposures disrespected aetiological factors. Odds ratio is determined

Question 10

Cross-sectional studies

Answer 10

Prevalence between different populations at a particular time. Mainly used for public health planning

Question 11

Purpose of medicolegal autopsies

Answer 11

To determine the cause of death, collect evidence for forensic investigations. To be performed by state forensic pathologist

Question 12

Purpose of clinical autopsies

Answer 12

To gather useful information but the cause of death particularly if the diagnosis was unclear. For example Kennedy samples

Question 13

Cell injury

Answer 13

A change or loss of function or morphology

Question 14

Necrosis

Answer 14

Caused by cell injury in particular as it disrupts cellular function

Question 15

Apoptosis

Answer 15

Programmed cell death that is more controlled by Intrinsic as well as extrinsic pathways

Question 16

When does a cell injury become irreversible?

Answer 16

When the injury persists always frequently re-occurring.

The lysosome breaks open meaning enzymes leak out and act on other organelles

Question 17

Changes that occur within the cell during injury

Answer 17

Karyolysis – the nucleus shrinks and eventually dissolutes.

Chromatin clumps caused by the degradation of DNA and nuclear condensation.

The ER and mitochondria swell.

Irreversible if:
The lysosomal breaks down causing enzymes to leak into the cell and agreed other organelles including ribosomes.

Question 18

Causes of cell injury

Answer 18

Oxygen deprivation, physical agents, chemical agents, infectious agents, immune responses, nutritional imbalances and genetic to arrangements

Question 19

Examples of oxygen deprivation

Answer 19

Hypoxia (lack of oxygen) and ischaemia (lack of blood flow)

Question 20

Examples of Physical agents

Answer 20

Mechanical trauma, extreme temperature such as burning or frostbite

Question 21

Examples of Chemical agents

Answer 21

Cyanide which blocks electron transport of cytochromes to cause respiratory failure, alcohol, carbon monoxide, acid burns

Question 22

Examples of Infectious agents

Answer 22

Viruses and bacteria

Question 23

Examples of Immune responses

Answer 23

Anaphylactic reaction to a protein, severe in for now response to Covid in the lungs

Question 24

Examples of Nutritional imbalances

Answer 24

Deficiencies of specific vitamins, malnutrition or obesity

Question 25

Examples of Genetic derangements

Answer 25

Sickle cell anaemia

Question 26

What does the Cellular response to stimuli depend on?

Answer 26

The type, severity and duration of injury

Question 27

What does the consequences of injury depend on?

Answer 27

To type, state and adaptability of injured cells

Question 28

ROS

Answer 28

Reactive oxygen species - Oxygen free radicals I have a single unpaired electrons in the outer shell

Question 29

ROS generation

Answer 29

Radiation is absorbed (such as x-rays from hospital imaging) which leads to redox reaction byproducts. Transition metals donate or accept free electrons during intracellular reactions including iron ions

Question 30

Nitric oxide (ONOO-)

Answer 30

And oxygen free radical that can generate other reactive oxygen species such as hydrogen peroxide

Question 31

Lipid peroxidation of membranes

Answer 31

Oxidative damage is initiated when double bonds in unsaturated fatty acids are attacked by oxygen free radicals

Question 32

Oxidative modification of proteins

Answer 32

Amino acid residues side chains are oxidised and form crosslinks such as disulphide bonds which results in fragmentation

Question 33

DNA damage caused by oxidation reactions

Answer 33

Reaction in thymine produces single-stranded breaks that can be passed on to the next generation of cells need to cancel

Question 34

Sequence of events in cell injury

Answer 34

Early reversible changes, irreversible changes and finally cell death by necrosis

Question 35

Early functional changes of cell injury

Answer 35

Decreased ATP generation, loss of cell membrane integrity, defective protein synthesis and cytoskeletal and DNA damage

Question 36

Morphological changes of reversible injury

Answer 36

Cellular swelling observed under light microscopy.

Plasma membrane blabbing, mitochondrial swelling, ER dilation and nuclear alterations observed under electron microscopy

Question 37

Morphological changes of irreversible injury

Answer 37

Extensively damaged cell membranes, lysozyme swelling, mitochondria vacuolisation, Entry of extracellular calcium ions and intracellular calcium release from stored versicles, enzyme activation better grades other organelles and leads to protein loss, nuclear changes

Question 38

Nuclear changes of irreversible cell injury

Answer 38

Pyknosis (shrinking), karyolysis (breakdown), karyorrhexis (fragmentation)

Question 39

Different types of necrosis in tissues

Answer 39

Coagulative (most common), liquefactive, caseous and fat necrosis

Question 40

Coagulative necrosis

Answer 40

Results from hypoxic cell death in all tissues except the brain. Maintain cell structure but nucleus is lost. Cytoplasm appears coagulative and stains pink with eosin

Question 41

Liquefactive/colliquative necrosis

Answer 41

Results from focal bacterial infection (accumulation of inflammatory cells). Hypoxic cell death in the brain. Tissues become a liquid viscous mass that accumulates dead white cells and is called pus

Question 42

What is pus

Answer 42

And accumulation of dead white cells

Question 43

Caseous necrosis

Answer 43

Results from focal TB infections. Tissue is completely alliterated to leave a cheesy white appearance

Question 44

Fat necrosis

Answer 44

Results from Fat destruction typically in acute pancreatitis that was brought about by pancreatic lipases acting on the pancreas and the peritoneal cavity. White chalky deposits form at the sites representing calcium deposition

Question 45

Reduced apoptosis results in …

Answer 45

Tumours formation - neoplasia

Question 46

Increased apoptosis results in…

Answer 46

Tissue shrinkage

Question 47

Characteristics of apoptotic cells

Answer 47

Cytoskeleton degradation, DNA fragmentation, mitochondrial function loss, nucleus shrinkage and fragmentation, apoptotic bodies, phagocytosis induction

Question 48

Apoptotic bodies

Answer 48

vesicles with intra cellular dying components and proteins