1. Cell Injury

Question 1

What is pathology the study of?

Answer 1

What went wrong.

Question 2

What is disease a consequence of?

Answer 2

Failed homeostasis with consequent morphological and functional disturbances.

Question 3

What does the degree of cell injury depend on?

Answer 3

Type of injury, severity of injury, and type of tissue.

Question 4

What are some common causes of cell injury and death?

Answer 4

Hypoxia, toxins, physical agents, radiation, micro-organisms, immune mechanisms, dietary insufficiency and deficiencies or excess.

Question 5

What are the four main causes of hypoxia?

Answer 5

Hypoxaemia hypoxia - arterial content of oxygen is low, from altitude.
Anaemic hypoxia - decreased ability of haemoglobin to carry oxygen.
Ischaemic hypoxia - interruption to blood supply, from heart failure.
Histiocytic hypoxia - inability to utilise oxygen in cells due to disabled oxidative phosphorylation enzymes, from cyanide poisoning.

Question 6

How do neurones and fibroblasts differ in terms of how long they can tolerate hypoxia for before cell death or permanent damage?

Answer 6

Neurones - a few minutes.

Fibroblasts - a few hours.

Question 7

Name two examples of toxin that can cause cell injury and death.

Answer 7

High concentration of oxygen, glucose and salt in hypertonic solutions, poisons, pollutants, insecticides, etc.

Question 8

How can the immune system damage cells?

Answer 8

Hypersensitivity reactions where the host tissue is injured secondary to an overly vigorous immune reaction like with hives - inflammation in the skin.
Autoimmune reactions where the immune system fails to distinguish self from non-self, e.g. Graves disease.

Question 9

What are the four principal targets for cell damage?

Answer 9

Cell membranes, nucleus, proteins, and mitochondria.

Question 10

What happens in the cell in hypoxia?

Answer 10

Mitochondria reduce oxidative phosphorlyation so less ATP is made. This means the Na+ pump has less action so there is an influx of Ca2+, H2O and Na+ and an efflux of K+ which leads to cellular swelling etc. The lack of ATP means there has to be more glycolysis so pH decreases, as do glycogen stores. Low ATP means ribosomes detach from the endoplasmic reticulum so there is less protein synthesis and lipid deposition.

Question 11

What are free radicals?

Answer 11

Reactive oxygen species with a single unpaired electron in an outer orbit. It is unstable and highly reactive to produce more free radicals.

Question 12

What are the three most biologically significant free radicals?

Answer 12

OH* - hydroxyl.
O2- - superoxide.
H2O2 - hydrogen peroxide.

Question 13

How can free radicals be generated from H2O?

Answer 13

Radiation: H2O -> OH* + H*.

Question 14

What is the Fenton reaction?

Answer 14

Fe2+ + H2O2 -> Fe3+ + OH- + OH*.

Question 15

What is the Haber-Weiss reaction?

Answer 15

O2- + H+ + H2O2 -> O2 + H2O + OH*.

Question 16

Why are lipids in the cell membranes a good target for free radicals?

Answer 16

It causes lipid peroxidation, this leads to further generation of further free radicals.

Question 17

How do free radicals cause injury of proteins, carbohydrates, and DNA?

Answer 17

Causes the molecules to bend out of shape, so they become cross-linked. They’re then mutagenic.

Question 18

How does the body respond to free radicals?

Answer 18

Uses anti-oxidant system to remove them. Using: enzymes, free radical scavengers, or storage proteins.

Question 19

How does reperfusion after ischaemia cause injury?

Answer 19

If blood returns to damaged but not yet necrotic tissue, the damage is worse than if the blood flow hadn’t returned. From increased production of oxygen free radicals with reoxygenation, more neutrophils so more inflammation and injury, and delivery of complement proteins and activation of the complement pathway.

Question 20

What is the role of heat shock proteins?

Answer 20

Protection against cell injury. They mend or destroy mis-folded proteins to maintain cell viability.

Question 21

What is oncosis?

Answer 21

Cell death with swelling. The spectrum of changes that occur in injured cells prior to death.

Question 22

How does oncosis present in light microscopy?

Answer 22

The cells have failed membrane and permeability so the cells shrink and the nucleus fragments.

Question 23

How does reversible cell injury present in electron microscopy?

Answer 23

Generalised swelling, clumping of chromatin, autophagy of lysosomes, ER and mitochondrial swelling, blebs.

Question 24

How does irreversible cell injury present in electron microscopy?

Answer 24

Rupture of lysosomes and autolysis, defects in cell membranes, myelin figures, lysis of ER, nucleus pyknosis, karyolysis or karyorrhexis.

Question 25

What is necrosis?

Answer 25

The morphological changes in a living organism that occur after a cell has been dead some time.

Question 26

What is apoptosis?

Answer 26

Cell death with shrinkage, programmed by the cell.

Question 27

What are the major differences between apoptosis and oncosis?

Answer 27

Apoptosis is ATP dependent, oncosis is ATP independent. Apoptosis has cell shrinkage, but oncosis has cell swelling.

Question 28

What are the two main types of necrosis?

Answer 28

Liquefactive and coagulative.

Question 29

What are the two prominent types of necrosis in clinical practice?

Answer 29

Caseous and fat necrosis.

Question 30

How are protein denaturation and enzyme release linked to liquefactive and coagulative necrosis?

Answer 30

Liquefactive necrosis has more enzyme release, coagulative has more protein denaturation.

Question 31

How does caseous necrosis present?

Answer 31

Contains amorphous/ structureless debris. Associated with infections like tuberculosis.

Question 32

What is fat necrosis from?

Answer 32

The destruction of adipose tissue, releases fatty acids that react with calcium to form chalky deposits in the tissue.

Question 33

What are the two types of gangrene?

Answer 33

Dry and wet (one subtype is gas gangrene).

Question 34

What is the difference between white and red infarct?

Answer 34

White infarct has no blood in it, occurs at end artery sites, coagulative necrosis. Red infarct is haemorrhagic so has lots of blood in it, in organs with dual blood supply.

Question 35

What do the consequence of infarcts depend on?

Answer 35

Alternative blood supply, speed of ischaemia, tissue involved and oxygen content of the blood.

Question 36

What is a physiological use of apoptosis?

Answer 36

Sculpting in embryology.

Question 37

When is apoptosis pathological?

Answer 37

When the cell is damaged and needs to be removed.

Question 38

What are the stages of structural change in apoptosis?

Answer 38

Normal cell -> condensation -> fragmentation -> apoptic bodies.

Question 39

What are the three phases of apoptosis?

Answer 39

Initiation, execution and degradation and phagocytosis.

Question 40

What happens in intrinsic initiation and execution of apoptosis?

Answer 40

DNA damages means p53 is activated. The mitochondria is a key player in this, it releases apoptosomes that activate caspase-9 and promote apoptosis.

Question 41

What happens in extrinsic initiation and execution of apoptosis?

Answer 41

It's outside the cell and leads to activated caspase-8 leading to apoptosis.

Question 42

What are the changes in a cell over degradation and phagocytosis in apoptosis?

Answer 42

Loss of microvilli and junction and nuclear changes. Then apoptic body and fragmentation. Phagocytosis and apoptic bodies are separated.

Question 43

What are some key apoptic molecules?

Answer 43

p53 - in response to DNA damage. Cytochrome c, APAF1, caspase 9 - apoptosome. Bcl-2 - inhibits apoptosis by preventing mitochondrial release of cytochrome c. Death ligands. Death receptors. Caspases - effector molecules of apoptosis.

Question 44

What can abnormal accumulations be a result of?

Answer 44

Cell's own metabolism, extracellular space, the outer environment.

Question 45

What are the five main groups of intracellular accumulations?

Answer 45

Water and electrolytes, lipids, carbohydrates, proteins and pigments.

Question 46

What is dystrophic calcification?

Answer 46

Local calcification.

Question 47

What is a cause of pathological metastatic calcification?

Answer 47

Destruction of bone in bone cancers or parathyroid tumours.