Substances accumulate intracellular or extracellular by dr.khadija university of taiz

2. Def.:
❑ Abnormal deposition of calcium salts in sites other than
bone& teeth.
Gross:
Chalky white & hard.
Microscopic
a basophilic , amorphous granular, sometimes clumped
appearance
➢ intracellular, extracellular, or in both locations.

3. Types of pathological calcification
Dystrophic calcification
Normal blood calcium
Metastatic calcification
↑blood calcium(hypercalcimia)

5. ❑ Pathological deposition of calcium salts in
dead or degenerated tissues with normal
calcium metabolism and normal level
calcium in the blood .

6. Pathogenesis :
▪ break down of organic phosphates →
change of PH (alkaline) of dead or
degenerated tissue + ↑alkaline phosphates
activity → calcium deposition.

7. Examples:
(1)In injured (degenerated) tissues as:
(a) Atheroma.
(b) Degenerative valves as in chronic rheumatic valvulitis.
(c) Degenerated tumors (as leiomyoma ,meningioma).
(2) ln necrotic tissues as:
✓Old scar.
✓Fat necrosis.
✓Caseous tuberculous lesions.
✓Dead parasites as bilharzia ova and worms.
✓Lithopedion (a calcified retained foetus).

11. Def.
❑ Pathological deposition of calcium salts in normal
tissues due to hypercalcaemia (↑serum level of
calcium) .
Sites:
calcium deposited in normal tissue as:
alveoli , gastric mucosa ,blood vessels & kidney.
Morphology as dystrophic calcification.

12. Causes:
Elevation of the blood calcium level due to:
❖ Excessive mobilization of calcium from the bone:
1) Primary hyperparathyroidism due to tumor.
2) Secondary hyperparathyroidism due to chronic renal
disease.
3) Destructive disease of Bone (multiple myeloma,
metastatic tumor)
❖Excessive absorption of calcium from the gut:
1) Hypervitaminosis D →↑↑ absorption of ca from GIT

13. Calcinosis
(Idiopathic calcinosis)

14. Def.
❑ A rare type of pathological calcification of unknown
cause.
Site:
❑ Calcium salt is deposited in the skin & subcutaneous
tissue forming tumor like swelling.

16. Extracellular
accumulation

18. Def.:
❑ Is a pathologic proteinaceous substance, deposited in
the extracellular space in various tissues and organs
of the body :
Site:
➢ Intercellular.
➢ Wall of blood vessels.
➢ Basement membrane.

19. Nature:
• 95% protenious material fibrial& 5% glycoprotein (P
component )
• The amyloid fibril are 2 types:
(1) Immunoglobulin (AL amyloid light chain) :
✓ Abnormal plasma cells→ abnormal Ig engulf by macrophage→
enter in their lysosomes → degraded into in soluble fibril
protein → amyloid light chain protein.
✓ In case neoplasm of plasma cells as multiple myeloma,
plasacytoma.

20. (2) Non immunoglobulin (AA amyloid-associated)
Chronic disease → toxemia→ detoxification by liver →
abnormal fibril proteins AA → amyloid associated protein.
1. As in chronic suppuration: bronchiectasis, chronic
osteomyelitis
2. Granuloma :syphilis.
3. Autoimmune disease as ulcerative colitis.
4. Gastric carcinoma ,lymphoma.
(3) AB2 amyloid as (B2 microglobulin) protein in case
of cerebral amyloidosis

21. Classification of amyloidosis
Systemic amyloidosis
Localized amyloidosis

22. Systemic amyloidosis
1) Primary amyloidosis (AL):
Cause: unknown
Associated with: multiple myeloma ,plasma cell
dyscriasis.
Site: heart . tongue, GIT,& kidney
2) Secondary amyloidosis(AA):
Cause: secondary to chronic disease
Disease:
1) Chronic suppurative lung disease
2)Chronic suppurative osteaomylitis
3)Chronic tuberculosis
4)Chronic ulcerative colitis

23. 1) Chronic malaria
2)Rheumatoid arthritis
3)Tertiary stage of syphilis
Site: liver ,spleen,kidney ,adernal gland.
3) Hemodialysis associated amyloidosis:
4) Hereditary form of amyloidosis: occurs in familial
Mediterranean fever.
• ;

24. Localized amyloidosis
1) Endocrine: as microscopic deposits in
a) Thyroid medullary carcinoma
b) Pheochromacytoma
c) Pancreatic islet cell tumor,type 2 diabatic melltius
2) Senial:
a) Senial cardic amyliodosis
b) Senial cerberal amyliodosis alzaheimar ,encephalopathy
3) Tumor forming in
lung,larynex,tongue,skin,urinary bladder

25. Gross
➢ Affected organs are enlarge , firm. elastic in
consistency with sharp edge brown in color . Cut section
are flat translucent and waxy.
Microscopic:
➢ Amyloid is amorphous, refractile and eosinopholic with
H&E stain.

26. Staining of amyloid
Gross staining:
1)Lugol̓s iodine → dark
brown and the rest of tissue
pale yellow
2)Iodine &1% sulphuric
acid →blue.
Microscopic:
1) H&E stain: amyloid
appears homogenous &
eosinophilic.
2) Congo red stain : orang
red.
3) Metachromic stain :rose
red .

30. Diagnosis:
❑ Is made on biopsy and characterized of Congo red stain
and Thioflavin -T stains.
1) Congo red → under polarized light →amyloid deposits
show green birefringence.
2) Thioflavin -T→ under fluorescent microscope
→amyloid deposits show yellow
fluorescence.

31. Congo red

33. Affected organs
❖Kidney:
▪ Renal amyloidosis is the most common form and a major
cause of death in patients with amyloidosis.
▪ Amyloid is deposited in the wall of arterioles ,
basement membrane of glomerular capillaries &
collecting tubules diabetes insipidus.

35. ❖ liver
▪ Amyloid deposits are seen in the walls of blood
vessels at portal tracts→ anoxia in liver cells → fatty
change and portal hypertension.
▪ As well as deposits in the wall of blood sinusoids →
fatty change due to pressure atrophy of liver cells.

37. ❖ Spleen
Local Sago spleen
Deposits :
In the wall of central
arterioles in lymphoid
follicles
Effect:
Moderate splenomegaly
Diffuse amyloid spleen:
Deposits :
In the walls of sinusoids of red
pulp .
Fusion of deposits form large
geographic areas
Effect:
Marked splenomegaly.

41. ❖ Heart
• The typical pattern is subendocardial amyloid
deposits particularly in the atria, also amyloid
deposits progressively occurring between myocardial
fibers → pressure atrophy → heart failure

43. ❖ Small intestine
• Deposits in villi around blood vessels →
malabsorpation syndrome.
❖Adrenal glands → Addison's disease.