Pathologic calcification, Cell aging

2. Learning objectives
• Pathologic calcification
• Hyaline change
• Cell aging!

3. PATHOLOGIC
CALCIFICATION

4. • Abnormal tissue deposition of calcium salts,
together with smaller amounts of iron,
magnesium, and other mineral salts

5. DYSTROPHIC
CALCIFICATION
METASTATIC
CALCIFICATION
1. Occurs locally in dead
and degenerated
tissues
2. Normal levels of serum
calcium
3. Absence of
derangements in
calcium metabolism
Examples – Psammoma
bodies in papillary
cancers, Asbestos bodies
Can cause organ dysfunction
(heart valves,
Atherosclerosis)
1. Deposition in normal
tissues
2. Increased levels of
serum calcium
3. Disturbance in
calcium metabolism
(in hyperparathyroidism,
bone damage or
diseases, William’s
syndrome

6. CALCIFICATION IN
DEAD TISSUES
1. Necrosis
2. Infarcts
3. Thrombi
4. Hematomas
5. Dead parasites
CALCIFICATION IN
DEGENERATED TISSUES
1. Dense old scars
2. Atheromas
3. Monckeberg’s
sclerosis
4. Stroma of tumors
5. Cyst walls
DYSTROPHIC CALCIFICATION

7. DYSTROPHIC CALCIFICATION
1. 2 Phases
1. Initiation – occurs in the mitochondria of
necrotic cells with the creation of a microcrystal
2. Propagation – accumulation of Ca+2 phosphate
salts
Although it may just be a sign of past injury it often
results in organ dysfunction

8. Dystrophic Calcification
Dystrophic calcification
in the Achilles tendon
after repeated
traumatic injury.

9. • Morphology =Basophilic, amorphous or
granular appearance intracellular,
extracellular or both in H & E stained sections

11. Psammoma Bodies

12. METASTATIC CALCIFICATION
1. 4 Primary causes
1. Elevated PTH causing bone resoption
1. Primary hyperparathyroidism
2. Secondary hyperparathyroidism
2. Destruction of bone
3. Vitamin D related disorders intoxication, Sarcoidosis
(macrophages turn on Vita D receptor)
4. Renal failure (phosphate retention so increased PTH)
2. Occurs throughout the body but favors tissues that
lose acid (alkali) favoring calcium deposition
(gastric mucosa, lungs, kidneys)

13. PATHOGENESIS
• Excessive binding of inorganic phosphate
ions with the calcium ions
• Precipitation of calcium phosphates

15. Hyaline change

16. • This is an alteration
• within cells or extracellular space
• Homogeneous glassy pink appearance
in H& E stains

17. • Its just a descriptive term
• rather than a specific marker of cell
injury!!

18. Intracellular
• Mallory body
• Russel body
• Zenkers degeneration in
rectus muscle .. In
typhoid
Extracelular
• Collagenous fibrous
tissue
• Change in leiomyoma
• Hyaline membrane
• Hyalinization in chronic
glomerulonephritis
• Corpora amylaceae

19. Cell aging

20. • There is good evidence that aging-induced
alterations in cells are an important
component of the aging of the organism

21. • Cellular aging is the result of a progressive
decline in cellular function and viability
– caused by genetic abnormalities
&
– the accumulation of cellular and molecular
damage due to the effects of exposure to
exogenous influences

22. changes that contribute to cellular
aging
• Decreased cellular replication.
• Accumulation of metabolic and genetic
damage.

23. Telomeres and Aging:
Is there a connection?

24. What are telomeres?
• Telomeres are…
– Repetitive DNA sequences at the ends of all
human chromosomes
– They contain thousands of repeats of the six-
nucleotide sequence, TTAGGG
– In humans there are 46 chromosomes and
thus 92 telomeres (one at each end)

25. What do telomeres do?
• They protect the chromosomes.
• They separate one chromosome from
another in the DNA sequence
• Without telomeres, the ends of the
chromosomes would be "repaired",
leading to chromosome fusion and
massive genomic instability.

26. Telomere function, cont’.
• Telomeres are also thought to be the
"clock" that regulates how many times an
individual cell can divide.
• Telomeric sequences shorten each time
the DNA replicates.

27. How are telomeres linked to
aging?
• Once the telomere shrinks to a certain
level, the cell can no longer divide. Its
metabolism slows down, it ages, and dies.
• SENESCENCE

28. Telomeres & Aging
• Healthy human cells are MORTAL
because they can divide only a finite
number of times, growing older each time
they divide. Thus cells in an elderly person
are much older than cells in an infant.

29. What is telomerase, anyway?
• Telomerase (TEE-LÓM-ER-ACE) is a
ribonucleoprotein enzyme complex (a cellular
reverse transcriptase) that has been referred to
as a cellular IMMORTALIZING enzyme.
• It stabilizes telomere length by adding
hexameric (TTAGGG) repeats onto the telomeric
ends of the chromosomes, thus compensating
for the erosion of telomeres that occurs in its
absence.

30. How Does Telomerase Work?
• Telomerase works by adding back
telomeric DNA to the ends of
chromosomes, thus compensating for
the loss of telomeres that normally
occurs as cells divide.
• Most normal cells do not have this
enzyme and thus they lose telomeres
with each division.

31. How Does Telomerase Work?
• In humans, telomerase is active in germ
cells, in vitro immortalized cells, the vast
majority of cancer cells and, possibly, in
some stem cells.
• High telomerase activity exists in germ
cells, stem cells, epidermal skin cells,
follicular hair cells, and cancer cells.

32. HOW TO
PROLONG LIFE SPAN
!!!!!!

33. CALORIE RESTRICTION!!!
• YES!
• Studies in model organisms, from yeasts
to mammals
• HOW?

34. • Mediated by family of proteins called
SIRTUINS!
• Promotes expression of several genes
whose products increase longevity
• Increase metabolism, reduce
apoptosis, decrease the effects of free
radicals

35. • constituent of red wine may activate
SIRTUINS and thus increase life span!

36. • Relevance of these findings to aging in
humans is an area of active
investigation!!!!.

39. Thank
you