These are simplified slides from the third and last lecture in a three-lecture series by Dr. Sidra Arshad, diving into the significance of genetic control which stands as one of the most intricate, yet complex, physiological control mechanisms intimately interlinked with homeostasis and cellular functioning. Learning objectives: 1. Describe the control of cell reproduction by telomeres and telomerase 2. Compare and contrast apoptosis and necrosis 3. Discuss the pathophysiology of cancer and ageing Study Resources: 1. Chapter 3, Guyton and Hall Textbook of Medical Physiology, 14th edition 2. Chapter 3, Human Physiology From Cells to System by Lauralee Sherwood, 9th ed 3. Chapter 1, Ganong’s Review of Medical Physiology, 26th edition 4. Apoptosis: physiological cell death and its role in pathogenesis of diseases, https://pubmed.ncbi.nlm.nih.gov/14558480/ 5. Cell signaling, https://blog.cellsignal.com/cell-process-what-role-do-the-telomeres-play-in-senescence

1. Module II, Block I
Cell and Genetics
Genetics III
Dr. Sidra Arshad
Assistant Professor
MBBS, FCPS (Physiology)

2. Learning Objectives:
1. Describe the control of cell reproduction by telomeres and
telomerase
2. Compare and contrast apoptosis and necrosis
3. Explain the pathophysiology of cancer and ageing
Dr. Sidra Arshad

3. • Some cells grow and reproduce all the time, such as:
blood-forming cells of the bone marrow
germinal layers of the skin
epithelium of the gut
Germ cells (spermatozoa and oocytes)
• Some cells cannot, such as:
neurons
striated muscle cells
Dr. Sidra Arshad

4. Liver has a remarkable ability to
restore itself after significant
hepatic tissue loss
Dr. Sidra Arshad

5. • The cell growth and cell reproduction are controlled by:
1. Growth factors from other parts of the body and from the growing
tissues themselves
2. Space available for growth
3. Control of cell replication by telomeres and telomerase
Dr. Sidra Arshad

6. • Telomeres are structures made
from DNA sequences and
proteins found at the ends of
chromosomes
• They cap and protect the end of
a chromosome from
deterioration during cell division
• Disposable chromosomal
buffers
Dr. Sidra Arshad

7. During cell division, a primer RNA attaches to the DNA strand to start
replication
Primer does not attach at the very end, causing the copied DNA to miss a
small section
Copied DNA loses additional nucleotides from the telomere region with
each cell division
Dr. Sidra Arshad

8. • Telomeres provide nucleotide
sequences preventing the degradation
of genes near chromosome ends
• Without telomeres, genomes lose
information and are truncated after
each cell division
• Telomeres shorten with each cell
division until the cell stops replicating
Dr. Sidra Arshad

9. • Though, most cells of the body cannot
replicate indefinitely
• In the rapidly replicating cells, an enzyme
telomerase, adds bases to the ends of the
telomeres
• In cancer cells, telomerase is abnormally
activated, and telomere length is maintained
• The cancerous cells continue to replicate
themselves uncontrollably
Dr. Sidra Arshad

10. • Telomerase activity is typically low in most body cells
• Descendant cells with low telomerase activity inherit defective chromosomes
• Over generations, cells become senescent and cease dividing due to telomere
shortening - ageing
• Telomere shortening also occurs in diseases associated with inflammation and
oxidative damage
• Telomere shortening regulates cell proliferation and maintains gene stability
Dr. Sidra Arshad

11. Cell Differentiation
refers to changes in the
physical and functional
properties of cells as they
proliferate in the embryo to
form the different body
structures and organs
Dr. Sidra Arshad

12. Dr. Sidra Arshad
Control of Cell
Differentiation
selective repression of
gene promoters, not gene
loss
some DNA segments become so
condensed that they no longer
uncoil to form RNA molecules
during differentiation
the genome produce a
regulatory protein that
forever after represses a select
group of genes
Inductive processes contribute
to the development of organs
and structures in the embryo

13. Apoptosis
• When cells are no longer needed or become a threat to the organism
• They undergo a suicidal programmed cell death or apoptosis
• Occurs in tissues that are being remodeled during development, and in adults
such as the intestine and bone marrow and are replaced by new cells
• Programmed cell death, however, is normally balanced by formation of new cells
in healthy adults
Dr. Sidra Arshad

14. • This process involves a specific proteolytic cascade that causes the cell to:
shrink and condense
disassemble its cytoskeleton
alter its cell surface
• Cellular material is packed into vesicles (apoptotic bodies)
• Neighboring phagocytic cell, such as a macrophage, destroy the apoptotic bodies
and the cell
Dr. Sidra Arshad

15. The apoptotic process involves the activation of special enzymes known as
procaspases
Caspases
Activate other procaspases
Triggering a cascade that rapidly breaks down proteins within the cell
The cell dismantles itself, packing organelles into apoptotic bodies
Rapidly digested by neighboring phagocytic cells
Dr. Sidra Arshad

16. Dr. Sidra Arshad

17. Significance of Apoptosis
1. Predictable self-elimination of selected cells is a normal part of development (CNS,
removing webs between the fingers)
2. Apoptosis is important in tissue turnover in the adult body (enterocytes)
3. Programmed cell death plays an important role in the immune system
4. Undesirable cells that threaten homeostasis are typically culled from the body by
apoptosis (ageing, damage due to radiation)
5. Autoimmune/ neurodegenerative diseases
Dr. Sidra Arshad

18. Necrosis
• Enzymatic degradation and protein denaturation of cell due to exogenous injury
• Cells swell and intracellular components leak
• Accompanied by inflammatory process
• Surrounded cells also die
• Premature cell death
Dr. Sidra Arshad

19. Apoptosis and Necrosis – A Comparison
Apoptosis Necrosis
Programmed cell death Pre-mature cell death
Cells actively involved in their own death The dying cells are passive victims
Caspase dependent Caspases not involved
Localised process Adjacent cells also involved
Cytoplasmic shrinkage, cellular content
packaged into apoptotic bodies
Cells swell and rupture
No inflammatory process Accompanied by inflammatory process
Dr. Sidra Arshad

20. Cancer
• Cancer can result from mutations or abnormal activation of cellular genes
regulating cell growth and mitosis
• Proto-oncogenes, normal genes controlling cell adhesion and division, may
become oncogenes if mutated or excessively activated
• Antioncogenes, or tumor suppressor genes, present in all cells, counteract the
activation of specific oncogenes
Dr. Sidra Arshad

21. Only a minute fraction of mutated cells in the body lead to cancer because:
1. Most mutated cells have lower survival capability than normal cells
2. Normal feedback controls prevent excessive growth
3. The body's immune system often destroys potentially cancerous cells
before they develop into cancer
4. The simultaneous presence of several activated oncogenes is typically
necessary to induce cancer
Dr. Sidra Arshad

22. • The probability of mutations increases significantly with exposure to certain factors,
including:
Dr. Sidra Arshad
Ionizing radiation such as x-rays and gamma rays, predisposing individuals to
cancer by causing DNA strand ruptures
Chemical carcinogens Certain chemical substances, such as in cigarette smoke
Physical irritants Such as continued abrasion of the intestinal tract linings
Hereditary tendency Inheritance of one or more mutated cancerous genes,
requiring fewer additional mutations for cancer to develop
Oncoviruses such as hepatitis viruses, can cause liver carcinoma

23. Why do cancer cells kill?
Dr. Sidra Arshad

24. Ageing
Dr. Sidra Arshad

25. Study Resources
1. Chapter 3, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 3, Human Physiology From Cells to System by Lauralee Sherwood, 9th ed
3. Chapter 1, Ganong’s Review of Medical Physiology, 26th edition
4. Apoptosis: physiological cell death and its role in pathogenesis of diseases,
https://pubmed.ncbi.nlm.nih.gov/14558480/
5. Cell signaling, https://blog.cellsignal.com/cell-process-what-role-do-the-telomeres-
play-in-senescence
Dr. Sidra Arshad