Robbins 7th ed - Chapter 1 - Cell Adaptations, Injury & Death (1.5)

Question 0

Give some examples of physiologic causes of apoptosis.

Answer 0

• Programmed destruction of finger webbing in embryogenesis
• Hormone-dependent involution of tissues (e.g. Endometrium)
• Deletion of self-reactive lymphocytes in clonal deletion after binding of Fas-ligand

Question 1

What happens to the cell membrane in apoptosis?

Answer 1

As opposed to necrosis, the cell membrane remains intact, and there is no leakage of cellular contents. The membrane forms buds (like exocytosis), which bud off as apoptosis bodies, which are rapidly phagocytosed.

Question 3

Give some examples of pathological causes of apoptosis.

Answer 3

• Noxious stimuli (e.g. Heat, Hypoxia, Radiation) can damage DNA repair mechanisms, causing the cell to kill itself rather than risking mutation and malignant transformation
• Cell death in certain viral infections
• Cell death in tumours

Question 4

Between the Intrinsic and the Extrinsic pathways to apoptosis, which is the more predominant?

Answer 4

Mitochondrial pathway (Intrinsic). Remember that the mitochondria contain a complex array of pro-apoptotic proteins and anti-apoptotic proteins, and it is the balance of these (affected by growth factors and survival signals) that determines whether or not a cell undergoes apoptosis.

Question 5

Which cells express Fas-ligand?

Answer 5

Regulator T-cells that destroy self-reactive lymphocytes, and some cytotoxic T-cells that kill virally-infected cells.

Question 6

What is another name for Fas? Describe this receptor.

Answer 6

Also called the Death Receptor, Fas is a member of the TNF receptor family. It is a transmembrane receptor that has a cytosolic “death domain”. When Fas-ligand binds to Fas, the cytosolic death domain activates caspases, leading to apoptosis.

Question 7

Which pathway of apoptosis involves Fas and Fas-ligand?

Answer 7

The Extrinsic pathway (the Death-Receptor initiated pathway)

Question 8

What are perforins and granzymes, and what do they do?

Answer 8

These are found inside cytotoxic T-cells. When the T-cell recognizes foreign antigens on the surface of healthy cells, they release perforins, which forms pores in the infected cell’s membrane, thereby promoting entry of the granzymes, which activate cellular caspases, thereby inducing the effector phase of apoptosis.

Question 9

Give an overview of autophagy.

Answer 9

Autophagy is the process of a cell’s organelles excreting their contents into the cytosol, and then phagocytosing these contents. This newly-formed double-membrane “autophagosome” (also called an autophagic vacuole) then fuses with lysosomes to digest the contents. Autophagy is an adaptive response that occurs during nutrient deprivation, allowing the cell to cannibalize itself to survive.

Question 10

What is the basic pathogenesis of fatty liver? What is its proper name?

Answer 10

Fatty liver, or steatosis: This is an inability of the cell to remove fats, and so fats accumulate within the cell.

Question 11

Give an example of a disease involving accumulation of cytoskeletal proteins.

Answer 11

Alzheimer’s disease: accumulation of neurofilaments and other proteins: the neurofibrillary tangle. Alcoholic liver disease: liver cells accumulate keratin filaments.

Question 12

What is haemosiderin, and under what circumstances is it produced?

Answer 12

Haemosiderin is a yellow-brown pigment derived from haemoglobin, and it is one of the major storage forms of iron. When there is an excess of iron, ferritin aggregates to form haemosiderin granules, which is an aggregation of ferritin micelles.

Question 13

There are two types of pathologic calcification: Metastatic and Dystrophic. What are the key features of dystrophic calcification?

Answer 13

Dystrophic calcification is found in areas of necrosis, and commonly as depositions on heart valves. Notably, serum calcium is normal: there is no abnormality of calcium metabolism.

Question 14

In metastatic calcification, there is a raised serum calcium level (hypercalcaemia). Name four processes that can cause hypercalcaemia.

Answer 14

1 – Increased PTH, e.g. parathyroid tumour
2 – Resorption of bone tissue, e.g. due to primary bone cancer or diffuse bone metastases
3 – Vitamin D disorders, e.g. sarcoidosis, vitamin D intoxication
4 – Renal failure – causing retention of phosphate, leading to secondary hyperparathyroidism

Question 15

What is telomerase? In which cells is it found?

Answer 15

Telomerase is an enzyme, a specialized protein-RNA complex that maintains the length of telomeres during DNA replication. It replicates telomeres using its own RNA as a template. Telomerase is found in germ cells and stem cells, but absent from most somatic cells. Telomerase is reactivated in cancer cells, allowing them to replicate indefinitely.

Question 16

Give an example of pathologic hyperplasia for women, and an example for men. What is the basic underlying pathology?

Answer 16

Endometrial hyperplasia: caused by an imbalance of progesterone and oestrogen.
Benign Prostatic Hyperplasia: caused by an excess of androgens.
NB : Pathologic hyperplasia is in itself benign and reversible, but it has increased risk of developing into malignancy.

Question 17

True or false: Hypertrophy is brought about by swelling of cells.

Answer 17

False. Hypertrophy is brought about by increase in cellular structural components.

Question 18

True or false: Myocardial fibres can undergo either hyperplasia or hypertrophy in disease processes.

Answer 18

False. Myocardial fibres are non-dividing cells, so they cannot undergo hyperplasia.

Question 19

What is the basic cellular mechanism triggering hyperplasia?

Answer 19

Increased growth factors, causing increased transcription of certain genes.

Question 20

What is the basic cellular mechanism triggering hypertrophy?

Answer 20

Mechanical triggers (e.g. stretch), or Trophic triggers (e.g. IGF-1, angiotensin II), trigger increased transcription of certain genes, and thus the synthesis of cellular proteins.

Question 21

Describe what happens in muscle hypertrophy, with respect to proteins changing forms.

Answer 21

α-myosin chain is converted to β-myosin chain, reducing ATP use and therefore causing more energetically economical contraction.

Question 22

Name as many triggers of atrophy as you can.

Answer 22

Disuse (e.g. muscle atrophy in bedridden patients), Denervation, Ischaemia, Pressure (e.g. pressure sores), Loss of nutrition, Loss of endocrine stimulation (e.g. vaginal atrophy post-menopausally), Senile atrophy of brain/heart.

Question 23

During atrophy, what happens to intracellular proteins that are tagged with ubiquitin?

Answer 23

They are taken to an organelle called a proteasome for proteolytic degradation.

Question 24

True or false: Metaplasia is irreversible.

Answer 24

False. Metaplasia is reversible. HOWEVER, this is meant in reference to metaplasia of a cell population, rather than an individual cell. Once any particular stem cell has already become fully differentiated, that cell itself won’t change its differentiation pathway.

Question 25

Give a definition for metaplasia.

Answer 25

Metaplasia is a reversible change in which one differentiated cell type is REPLACED by another cell type, rather than actually transforming itself into another cell type.

Question 26

Give an example of pathologic columnar to squamous metaplasia.

Answer 26

Cigarette smokers’ respiratory tract, exposed to toxins.

Question 27

Give an example of pathologic squamous to columnar metaplasia.

Answer 27

Barrett’s Oesophagus: squamous cells of the oesophagus are replaced by columnar cells like the intestinal lining, in response to refluxed acid.

Question 28

Explain briefly how a lack of oxygen can cause a cascade of events, resulting in cell swelling?

Answer 28

Lack of oxygen –> reduced oxidative phosphorylation –> reduced ATP –> reduced Na/K/ATPase pumps –> changes in ion concentations –> cell swelling

Question 29

For each exchange of ions, how many sodium ions and how many potassium ions pass through the Na/K/ATPase pump?

Answer 29

Three sodium ions out, Two potassium ions in.

Question 30

Name four ways in which a cell can be deprived of oxygen.

Answer 30

1 - ischaemia
2 - low PaO2
3 - anaemia
4 - carbon monoxide poisoning

Question 31

Name 7 categories of causes of cell injury.

Answer 31

1 - Oxygen deprivation
2 - Physical agents (trauma, burns)
3 - Chemical (electrolytes, toxins, drugs)
4 - Immunologic
5 - Genetic (congenital or acquired DNA damage)
6 - Infectious agents
7 - Nutritional deficiencies

Question 32

What is coagulative necrosis?

Answer 32

This is the most common form of necrosis. The dead cells remain in place for days or weeks before being digested by leukocytes, and so the tissue architecture remains firm. A localized area of coagulative necrosis is called an infarct.

Question 33

What is liquefactive necrosis?

Answer 33

This occurs in the brain and in bacterial infections. Dead cells are digested by their own enzymes, and the necrotic tissue becomes a viscous liquid mass called pus.

Question 34

What is gangrenous necrosis? What is wet gangrene?

Answer 34

This is where an already necrotic tissue (usually coagulative) becomes infected with bacteria. If this then results in liquefactive necrosis, it is called “wet gangrene”.

Question 35

What is a common example of caseous necrosis?

Answer 35

Tuberculosis. “Cheese-like” necrosis.

Question 36

Name three different Reactive Oxygen Species.

Answer 36

Superoxide (O2- with one electron), Hydrogen Peroxide (H2O2) and Hydroxyl ions (OH-)

Question 37

What are caspases?

Answer 37

Caspases are a family of proteases that break down proteins during apoptosis.

Question 38

What is the difference between the “initiation phase” and the “execution phase” of apoptosis? Name two caspases that are initiators, and two that are executioners.

Answer 38

The initiation phase is when caspases become active, and the execution phase is when the enzymes cause cell death. Caspases 8 and 9 are initiators, whilst caspases 3 and 6 are executioners.

Question 39

What is the difference between the extrinsic and intrinsic pathways that trigger apoptosis?

Answer 39

The extrinsic pathway involves binding of a ligand to a “death receptor” (which is a member of the TNF family). The intrinsic pathway is when there is a withdrawal of growth factors or there is stress, which triggers the mitochondrial membrane to become more permeable. Proteins from within the mitochondria leak out, and activate caspases.

Question 40

What is the etymology of the word “caspase”?

Answer 40

“C” refers to an active site cysteine, and “aspase” refers to the unique ability to cleave after aspartic acid residues.

Question 41

What are residual bodies (in regard to atrophy)?

Answer 41

In atrophy, there is an increase in autophagic vacuoles as the cell tries to recycle its own material. Some cellular debris resists digestion, and persists as membrane-bound residual bodies, e.g. lipofuscin granules.

Question 42

In metastatic calcification, where does the calcium often deposit?

Answer 42

In tissues that excrete acid, and therefore have an internal alkaline medium that predisopses them to calcification, such as the gastric mucosa, kidneys and lungs.

Question 43

What is the relationship between retinoic acid and metaplasia?

Answer 43

Retinoic acid is also called Vitamin A, and it is a regulator of gene transcription. Deficiency or excess of retinoic acid alters gene transcription, and causes metaplasia.