This document discusses four pathways of abnormal intracellular accumulation: proteins, glycogen, pigments, and lipids. It provides details on different types of pigments including melanin, hemoglobin derivatives, porphyrins, and exogenous pigments. Specific examples of diseases associated with accumulation of each substance are mentioned, such as alpha-1 antitrypsin deficiency leading to protein accumulation and diabetes mellitus resulting in glycogen storage in the liver and pancreas. Testing methods like DOPA reaction and Prussian blue staining are also summarized.

1. +
Intercellular
accumulation

2. +
Introduction
 Manifestations of metabolic derangements in cells
 Accumulation of abnormal amounts of various substances
 Located in cytoplasm , organelles , nucleus
 Synthesized by the cells or produced elsewhere

3. +
Four pathways
of abnormal
intracellular
accumulation

4. +
Proteins
 Rounded , eosinophilic droplets , vacuoles or aggregates in the
cytoplasm
 Reabsorption droplets in proximal renal tubules – renal
disease.
 Alpha 1 antitripsin deficiency , no folding of proteins –
emphysema
 Neurofibrillary tangle – emphysema
 Amyloidosis – abnormal & misfolded proteins

5. +
GLYCOGEN
 Glucose or glycogen metabolism
 Clear vacuoles in cytoplasm
 PAS positive
 Diabetes mellitus : liver , beta cells of the islets of langerhans ,
heart.
 Glycogen storage disorder – enzyme defect.

6. +
DISORDERS OF
PIGMENT
METABOLISM
6

7. +
TYPES OF PIGMENTS
7
• They are coloured substances varying in chemical composition
• ENDOGENOUS (Manufactured by special cells of the body)
• EXOGENOUS (absorbed from outside).

8. +
ENDOGENOUS PIGMENTS
 Melanin
 Pigments derived from Hb
 Fat associated pigments
 Others.
8

9. +
THE MELANINS
• Normally gives color to
– Hair, skin eyes
– Adrenal medulla
– CNS- SN
. Microscopically ,melanin appears as brownish-black granules
9

10. +
Site of production
Melanoblasts (precursors)
↓
Melanocytes (basal layer of epidermis)
Origin – neural crest.
10

11. +
DOPA REACTION
Melanocytes contain enzyme tyrosinase which acts as
following:-
Tyrosine
↓ tyrosinase
Dihydroxy phenyl alanine
↓tyrosinase
Quinone
↓
Melanin.
11

12. +
USES OF DOPA REACTION
 Incubate melanocytes with tyrosine or DOPA gives rise to melanin
production
 Helps diagnose amelanotic melanoma.
12

13. + Factors affecting melanin distribution
 Site
 no of melanocytes in palmar epidermis < dorsum
 Racial
 ↑activity of melanocytes (not much ↑in no )in dark skinned
people
 Hormonal control
 Pituitary: secretes ACTH which has MSH like activity →may
result in dark skin.
 Adrenal gland: inhibits MSH activity
 Sex hormones:
 Estrogens causes ↑pigmentation
 Pregnancy
 OC pills
13

14. +
Abnormalities in pigmentation
 ↑ pigmentation:
 Generalized
 Localized
 ↓ pigmentation:
 Generalized
 Localized.
14

16. 16
•Albinism:

17. 17
Macule in Tuberculoid Leprosy

18. 18
•Vitiligo
•Vitiligo

19. 19
•Tinea versicolor.
Tinea versicolor

20. +
Pigments derived from Hb
 Haemoglobin
 Methaemoglobin
 Haemosiderin
 Haematoidin
 Haematin
 Bilirubin
 Porphyrins
 Haemazoin.
20

21. +
Synthesis of Hb
Porphobilinogin
↓
Protoporphyrin III
↓ferrous iron
Haem (Fe surrounded by porphyrin ring)
21

22. Catabolism of Haem
Haemoglobin →Haem + Globin
22
Fe containing fragment.
Goes to Fe stores mainly
as Haemosiderin
Non Fe containing
Haematoidin
Biliverdin
Bilirubin(carried to liver by albumin)
Conjugated by glucuronyl
transferase with glucronic
acid
Dissociates from albumin
Conjugated bilirubin
To protein stores
Urobilinogen in intestine
Carried back to liver
Exc in urine
Exc as stercobilin

23. + Storage iron
60% in Hb
5% in Myoglobin
0.25% in cells (cytochrome,catalase)
Rest in stores (ferritin and haemosiderin)
 Ferrous state {FERRITIN}
 16% Fe
 Combined with βglobulin (apoferritin)
 P.B negative
 Ferric state {HAEMOSIDERIN}
 24-45% Fe
 no protein
 PB positive.
23

24. +
Prussian blue reaction
 Section washed free from blood
 Dipped in 2% solution of K ferrocyanide
 Then in 1% HCl
 + ve test – Blue color
 Reaction:-
Ferric iron + 2% K ferrocyanide + 1% HCl → ferric ferrocyanide
(blue).
24

25. + Abnormalities with haemosiderin deposition
- Localized
 Hemorrhage – breakdown of RBCs – haemosiderin in
macrophages.
 Eg. organizing haematoma, fractures, sclerosing
haemangioma
 Renal tubules – Hb uria – breakdown of Hb to
haemosiderin – stored in renal tubules
 Pulmonary:
 Small hemorrhage
 occur in lung after MS or LVF
 Heart failure cells – haemosiderin in al macrophages
 Brown induration – followed by fibrosis in long standing cases
 Idiopathic in children and young adults
 Pulmonary haemosiderosis associated with AGN - Good
pastures syndrome.
25

26. 26
Brown coarsely granular material in macrophages in alveolus: Haemosiderin

27. 27
Prussian blue reaction: demonstrating large amounts of hemosiderin in liver cells

28. +Abnormalities with haemosiderin
deposition – Generalized
 When the body is Fe over loaded
 ↑Fe in diet (Bantu)
 Chronic haemolytic anemia
 Haemochromatosis (↑Fe abs)
 Parental Fe administration
 Repeated blood transfusion
 Parenchymatous
 Liver, pancreas, kidney, heart
 Reticulo-endothelial
 Liver, spleen, BM.
28

29. +
Haemochromatosis (bronze DM)
 AD
 Alteration in regulation of Fe absorbtion
 More in males, females protected by menstrual loss
 Seen (parenchymatous distribution)
 Liver cells – cirrhosis
 Pancreas – DM
 Skin – Bronze skin (melanin + lipofuschin deposits in sweat glands)
 Joints – polyarthritis (small joints of hands, wrists, elbow,hips knee, ankle).
29

30. +
Bilirubin
 Unconjugated
 Insoluble (held in sol by albumin)
 Indirect Van den bergs +ve
 Not excreted in urine
 Conjugated
 Water soluble
 Direct Van den bergs +ve
 Excreted in urine if ↑
30

31. +
Jaundice
 ↑ bilirubin
31

32. +
Changes in the organ
 Body tissues + fluids – stained yellow
 Liver – greenish
 Eyes – yellow
 Micro:
 Bile pigment in hepatocytes, kupffer cells, canaliculi
 Fibrosis in later stages
 Bile staining of basal ganglia – kernicterus, in children due to poorly
developed BBB.
32

33. 33
The yellow-green globular material seen in small bile ductules in
the liver here is bilirubin pigment. This is hepatic cholestasis.

34. +
Porphyrins
 Metabolic bi-products which has escaped from the path of
biosynthesis to haem
 Genetic/ acquired
 Deposited in teeth, bones & other tissues
 Urine – bright red .
34

35. +
Haemazoin
 Malarial pigment
 Resembles haematin
 PB -ve.
35

36. +
Pigments related to fat
 Lipochromes
 Ceroids
 Lipofushin.
36

37. + Lipofuschins
Peroxidation of unsaturated lipids
Endogenous brown granules
Called as wear and tear pigments:
 myocardial fibers
 liver cells
 epithelial cells
 seminal vesicles and prostate
 nerve cells
Brown atrophy of heart and liver
 seen in old age, malnutrition, wasting …..
Intestinal lipofuschinosis (malanosis coli)
 Vit E def, mal-absorption.
37

38. +
Lipochrome (lipofuscin): Yellow-brown granular pigment seen in the
38

39. +
Exogenous pigments
 Metals
 Argyria
 Chrysiasis
 Plumbism
 Mercury
 Arsenic
 Bismuth.
39

40. +
Exogenous pigments ……… contd
 Dusts:
 <5 nm, reach pul alveoli - alveolar macrophages
 Anthracosis – coal dust in lung
 Siderosis – inhalation of iron dust
 Tattoos:
 colored metallic organic dyes
 introduced in to the dermis
 lie within the histiocytes/ extacellular-reaches the
lymph node
 eg. India-ink, indigo, Pb.
40

41. 41
•Tattoos:

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