general pathology lecture for medical undergraduates

1. - Dr. Chiragkumar B Menapara
Assistant Professor
Dept. of Pathology
Competency No. Competency Name
PA 2.3 Intracellular accumulation of fat,
proteins, carbohydrates, pigments
PA 2.5 Describe and discuss Pathological
Calcification and Gangrene

2.  Classify intracellular accumulations
 Describe Fat accumulation (fatty change)
 Give examples of conditions in which protein &
carbohydrate accumulations occur
 Describe endogenous (Melanin, Hemoproteins,
lipofuscin) & exogenous (inhaled,ingested &
injected) pigment accumulations
 Define pathologic calcification
 Describe dystrophic & metastatic calcifications
 Define & describe gangrene.

3.  Under some circumstances cells may accumulate
abnormal amounts of various substances.
 They may be harmless or associated with varying
degrees of injury.

4.  May be found:
 in the cytoplasm
 within organelles (typically lysosomes)
 in the nucleus
 Came to the cell through:
 Synthesis by affected cells
 Produced elsewhere

5. 1. Normal or increased rate of production of a normal
substance, but metabolic rate is inadequate to
remove it (e.g. fatty change in liver)

6. 2. A normal or an abnormal endogenous substance
accumulates because of genetic or acquired
defects in its folding, packaging, transport, or
secretion.
e.g. In α-1antitrypsin deficiency,
α1at accumulates in the liver causing cirrhosis)

7. 3. An inherited defect in an enzyme may result in
failure to degrade a metabolite.
The resulting disorders are called storage diseases.

8. 4. An abnormal exogenous substance is deposited and
accumulates because the cell has neither the
enzymatic machinery to degrade the substance
nor the ability to transport it to other sites.
(e.g. Accumulations of carbon or silica particles)

9. Accumulation of Lipids

10.  Fatty change refers to any abnormal accumulation
of triglycerides within parenchymal cells.
 Site: liver, most common site
 It may also occur in heart, skeletal muscle, kidney, and
other organs.

11.  Toxins (most importantly: Alcohol abuse)
 Diabetes mellitus
 Protein malnutrition (starvation)
 Obesity
 Anoxia

13. Gross:
 With increasing accumulation, the organ
enlarges and becomes progressively yellow, soft,
and greasy.

15.  Early: small fat vacuoles in the
cytoplasm around the nucleus.
 Later stages: the vacuoles
coalesce to create cleared spaces
that displace the nucleus to the
cell periphery
 Occasionally contiguous cells
rupture (fatty cysts)

18. These macrophages may be
filled with minute,
membrane-bound
vacuoles of lipid, imparting
a foamy appearance to
their cytoplasm (foam
cells).

19. 2. Atherosclerosis:
Smooth muscle cells and macrophages are filled with lipid
vacuoles composed of cholesterol and cholesteryl
esters

20. 3. In hereditary and acquired hyperlipidemic
syndromes, macrophages accumulate intracellular
cholesterol
4. Xanthomas: clusters of foamy macrophages present
in the subepithelial connective tissue of skin or in
tendons

21.  Morphologically visible protein accumulations are
much less common than lipid accumulations
 They may occur because excesses are presented to
the cells or because the cells synthesize excessive
amounts

22. 1. Nephrotic syndrome:
 In the kidney trace amounts of albumin filtered
through the glomerulus are normally reabsorbed by
pinocytosis in the proximal convoluted tubules
 After heavy protein leakage, pinocytic vesicles
containing this protein fuse with lysosomes, resulting
in the histologic appearance of pink, hyaline
cytoplasmic droplets

23. The process is reversible; if the proteinuria abates, the protein
droplets are metabolized and disappear.

24. 2. Marked accumulation of newly synthesized
immunoglobulins that may occur in the RER of
some plasma cells, forming rounded, eosinophilic
Russell bodies.

25. 3. Mallory body, or "alcoholic hyaline," is an
eosinophilic cytoplasmic inclusion in liver cells that
is highly characteristic of alcoholic liver disease
These inclusions are
composed
predominantly of
aggregated intermediate
filaments

26. 4. The neurofibrillary tangle found in the brain in
Alzheimer disease is an aggregated protein
inclusion that contains microtubule-associated
proteins

27.  Associated with abnormalities in the metabolism of
either glucose or glycogen.
 Examples:
1. In poorly controlled diabetes mellitus, glycogen
accumulates in renal tubular epithelium, cardiac
myocytes, and β cells of the islets of Langerhans.

28. 2. Glycogen accumulates within cells in a group of
closely related genetic disorders collectively
referred to as glycogen storage diseases, or
glycogenoses
 In these diseases, enzymatic defects in the
synthesis or breakdown of glycogen result in
massive stockpiling, with secondary injury and cell
death.

29.  Pigments are colored substances in the organism or
environment.
 Exogenous : coming from outside the body
 Endogenous: synthesized within the body itself.

30. (1) Inhaled:
- Carbon or coal dust
- Silica or stone dust
- Iron or Iron oxide
- Asbestos

31. (1) Inhaled: - Carbon or coal dust
- The most common exogenous pigment
- Picked up by alveolar macrophages
- Causes blackening of the tissues of lung
(Anthracosis)
- Anthracosis + fibroblastic reaction = Coal workers
pneumoconiosis

34. (1) Inhaled: Silica or stone dust

35. (1) Inhaled: Asbestos
Asbestos bodies

36. (2) Ingested:
- Lead: Chronic lead poisoning, Blue line on gum
- Silver compounds: Argyria
- Certain cathartics: Melanosis coli
- Carrot: Carotenemia,
Yellow-red coloration of skin

39. (3) Inoculated/ Injected:
Tattooing – India ink, cinnabar or carbon are injected into
the dermis

40. Endogenous Pigments
Autogenous
Hemoproteins
Derived
Melanin
Homogentisic acid
Lipofuscin
Hemosiderin
Hematin
Bilirubin
Porphyrins

42. Generalised hyperpigmentation:
- Genetic
- Radiation ( UV )
- Addison’s disease
- Cushing’s syndrome/ ACTH production
- Acromegaly
- Certain drugs
- Malabsorption & Biliary cirrhosis

43. Focal/Patchy hyperpigmentation:
- Freckles
- Solar lentigo
- Chloasma/Melasma
- Post inflammatory pigmentation
- Acanthosis nigricans
- Café au lait spots in neurofibromatosis and
Albright’s synd
- Peri oral pigmentation in peutz-jeghers synd.
- Melanotic tumor- naevi & melanoma

46.  Black pigment
 Autosomal recessive
 Deficiency of homogentisic oxidase
 Homogentisic acid accumulates in tissue
(ochronosis)
& excreated in urine (Alkaptonuria)
 Ochronosis
 Black pigment deposit in skin, connective tissues, cartilage,
capsules of joints etc.

47.  Insoluble brownish-yellow granular pigment
accumulates near nucleus
 Inclusions of lipid peroxides, phosphates, proteins
 Accumulates in liver, heart, brain from normal
“wear and tear”
 Sign of free radical damage
 Indicative of age, oxidative damage
 Does not stain blue with Prussian blue or Perl’s iron
 When present in large amounts, imparts an
appearance to the tissue that is called brown
atrophy

49.  Formed by aggregates of ferritin
 Golden-yellow to brown granular pigment
 Prussian blue reaction
 Mononuclear phagocytes of the bone marrow, liver,
spleen.

50.  Develops whenever hemorrhage into the tissue
 The changing colors of a bruise or a black eye
 Brown induration of lung: mitral stenosis, left
ventricular failure
Oxyhemoglobin
Deoxyhemoglobin
Biliverdin
Bilirubin
Hemosiderin

51.  Systemic overload of iron may result in two types of
patterns:
(1) Parenchymatous deposition: Liver, pancreas, kidney,
heart
- Excessive intake of dietary iron
- Excessive intestinal absorption of iron
- Increased erythropoietic activity
- Impaired utilization of iron
(2) Reticuloendothelial deposition
- Repeated blood transfusion
- Parenteral iron therapy

52.  Autosomal dominant disease
 Excessive absorption of iron
 Triad of
- Pigmentary liver cirrhosis
- Pancreatic damage leads to DM
- Skin pigmentation

53. The iron can be unambiguously identified by the Prussian
blue histochemical reaction

54.  Brown colored pigment containing haem iron in ferric
form
 Formed by oxidation of Hb.
 Can’t be stained by prussian blue reaction
 Chronic malaria, mismatched blood transfusion

55.  Non-iron containing yellow colored pigment
 Bilirubin build-up in tissues (Jaundice)
 Prehepatic or hemolytic: due to excessive hemolysis
 build-up of unconjugated bilirubin
 Hepatic or hepatocellular: due to failure of at least 80% of
liver function
 both conjugated and unconjugated bilirubin accumulates
 Posthepatic or obstructive: due to failure of bile to drain into
GI
 Conjugated bilirubin accumulates

57.  Porphyra = purple
 Purple discolouration of feces and urine when exposed to light
 Porphyrins are tetrapyrroles, are intermediates of heme synthesis
 Porphyrias result from genetic deficiency of one of the enzymes
required for the synthesis of heme, so that there is excessive
production of porphyrins
 Two types:
1. Erythropoietic porphyrias
2. Hepatic porphyrias

58.  Deposition of calcium salts in tissues other than
osteoid or enamel is called pathologic or
heterotopic calcification.

59.  Dystrophic calcification:
 When the deposition occurs in dead or degenerated
tissues
 It occurs with normal calcium metabolism and normal
serum calcium level.
 Metastatic calcification:
 The deposition of calcium salts in normal tissues
 It almost always reflects some derangement in calcium
metabolism (hypercalcemia).

60. Gross:
 Only be detected grossly if extensive.
 If grossly evident, calcification appears as pale chalky
areas (granules or clumps) in the tissues.
 Even if not visible, calcification can sometimes be
detected by the coarse gritty feel of the tissues when
scraped or incised with a knife or scalpel blade.
 Sometimes a tuberculous lymph node is essentially
converted to radio-opaque stone.

61. Histologically
 Calcification appears as intracellular and/or
extracellular deeply basophilic, irregular and granular
clumps.
 In larger deposits, only the rim stains basophilic while
the bulk of the internal core is eosinophilic (pink).
 Sometimes, single necrotic cells act like little grains of
sand around which a “pearl” of calcium is deposited.
This is called a psammoma body
 Confirmed by special stains:
- silver impregnation method of von-Kossa
producing black colour
- alizarin red S produces red staining.

63. Etiology:
- In Dead tissue
1) Caseous necrosis: the most common site for dystrophic ca.
2) Liquefaction necrosis in chronic abscesses
3) Fat necrosis (acute pancreatitis or traumatic)
4) Infarct
5) Gamna-Gandy bodies: calcific deposits admixed with
haemosiderin on fibrous tissue.
6) Thrombi especially in the veins, may produce phleboliths.
7) Hematomas (esp. in the vicinity of bones)
8) Dead parasites: hydatid cyst, Schistosoma eggs, and cysticercosis
9) Foreign substances: Asbestosis- calcium and iron salts gather
about long slender spicules of asbestos
10) Calcification in breast ca.
11) Congenital Toxoplasmosis

65. Etiology:
- In degenerated tissue
1) Dense old scars: hyaline degeneration f/b calcifications
2) Atheroma
3) Monckeberg’ sclerosis
4) Stroma of tumors: uterine fibroids, breast cancer,
thyroid adenoma, goitre
5) Cysts of long duration: epidermal and pilar cysts.
6) Calcinosis cutis: irregular nodular deposits of calcium salts
in the skin and subcutaneous tissue
7) Senile degenerative changes: costal cartilages, tracheal or
bronchial cartilages, and pineal gland
8) Psammoma bodies

68. Etiology:
 Excessive mobilisation of calcium from the bone.
 Excessive absorption of calcium from the gut.

69. Etiology:
 Excessive mobilisation of calcium from the bone
- Hyperparathyroidism
- Bony destructive lesions
- Hypercalcaemia as a part of paraneoplastic syndrome
- Prolonged immobilisation: disuse atrophy of the bones
and hypercalcaemia.

70. Etiology:
 Excessive absorption of calcium from the gut
- Hypervitaminosis D: Excess vit D intake
(overdose) or sarcoidosis
- Milk-alkali syndrome
- Idiopathic hypercalcaemia of infancy (Williams
syndrome)
- Renal causes such as in renal tubular acidosis

71.  Metastatic calcification can occur widely throughout
the body but principally affects the interstitial tissues of
the vasculature (systemic arteries, and pulmonary
Veins), kidneys, lungs, and gastric mucosa, cornea,
synovium
 All these tissue excrete acid and therefore have internal
alkaline compartment that predispose them to
metastatic calcification.
 Calcium binds with phosphate, this leads to precipitates
of calcium phosphate at the preferential sites
 Metastatic calcification is reversible upon correction of
underlying metabolic disorder.

72. The calcium deposits morphologically resemble those
described in dystrophic calcification.
 Kidneys: basement membrane of tubular epithelium
and in the tubular lumina causing nephrocalcinosis
 Lungs: in the alveolar walls.
 Stomach: on the acid-secreting fundal glands.
 Blood vessels: on the internal elastic lamina.

73. 

75.  Definition: Necrosis of tissue associated with superadded
putrefaction
 Three forms
- Dry Gangrene
- Wet Gangrene
- Gas Gangrene

76. Dry Gangrene
 Site: Distal part of a limb
 Causes: arteriosclerosis, TAO, Burger’dis, Raynaud’
dis. ,trauma, ergot poisoning
 Line of separation
 Pathological changes:
- Gross: dry, shrunken and dark black, resembling the
foot of a mummy
- M/E: Coagulative necrosis with smudging of tissue.
The line of separation consists of inflammatory
granulation tissue

77. Wet Gangrene
 Site: In naturally moist tissues and organs such as the
bowel, lung, mouth, cervix, vulva. Diabetic foot due to
high glucose content. Bed sores in a bed-ridden patient
 Causes: Blockage of both venous return as well as arterial
blood flow
 Toxic products…..
 No line of separation
 Pathological changes:
- Gross: soft, swollen, putrid, rotten and dark
- M/E: coagulative necrosis with stuffing of affected part
with blood. Intense acute inflammatory exudates

78. Gas Gangrene – form of wet gangrene caused by gas
forming clostridia
 Cause: clostridia (gram-positive anaerobic bacteria)
 Site: open contaminated wounds, as a complication of
operation on colon
 Pathological changes:
- Gross: swollen, oedematous, painful and crepitant due to
accumulation of gas bubbles
- M/E: coagulative necrosis with liquefaction, Large number
of gram-positive bacilli, leucocytic infiltration, oedema
and congestion