cell injury : intracellular accumulations
TRANSCRIPT
![Page 1: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/1.jpg)
![Page 2: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/2.jpg)
Learning objectives
• Intracellular accumulations
– Fatty change– Proteins– Carbohydrates– pigments
![Page 3: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/3.jpg)
Intracellular accumulations
![Page 4: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/4.jpg)
Intracellular accumulations• Manifestation of metabolic derangement• Accumulation may be transient & reversible or
permanent. Effects: range from harmless to toxic• Three categories
![Page 5: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/5.jpg)
Accumulations of Constituents of
Normal Cell metabolism
Accumulations of Abnormal substances
ofabnormal
Cell metabolism
Accumulations of pigments
Fats
Proteins
Carbohydrates
Storage diseases
Inborn errors of metabolism
Endogenous pigments
Exogenous pigments
ACCUMULATIONS
![Page 6: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/6.jpg)
Mechanisms of intracellular accumulations
Alpha 1 antitrypsin deficiency
![Page 7: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/7.jpg)
![Page 8: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/8.jpg)
FATTY CHANGE• Steatosis• Fatty metamorphosis
• Intracellular accumulation of neutral fat(triglycerides) within the parenchymal cells.
• Common in liver• Can occur in heart, skeletal muscle and
kidneys.
![Page 9: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/9.jpg)
• Causes of fatty liver • - ALCHOL ABUSE
• - DIABETES MELLITUS
• - OBESITY
• - PROTIEN MALNUTRION (starvation)
• -DRUGS/TOXINS
• -ANOXIA
• -PREGNANCY
![Page 10: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/10.jpg)
Excessive entry of lipids into the liver
Enhanced fatty acid synthesis by hepatocytes
Decreased oxidation of fatty acids by mitochondria
Increased esterification of fatty acids to triglycerides
Decreased apoprotein synthesis
Impaired lipoprotein excretion
![Page 11: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/11.jpg)
SizeCapsuleMarginsColor
GROSS
![Page 12: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/12.jpg)
![Page 13: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/13.jpg)
![Page 14: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/14.jpg)
![Page 15: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/15.jpg)
![Page 16: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/16.jpg)
![Page 17: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/17.jpg)
![Page 18: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/18.jpg)
Fat stains
• Can be demonstrated in fresh unfixed tissue by frozen section
![Page 19: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/19.jpg)
![Page 20: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/20.jpg)
![Page 21: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/21.jpg)
![Page 22: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/22.jpg)
![Page 23: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/23.jpg)
Other Lipid Accumulations
• Cholesterol and cholesterol esters – In atherosclerosis, cholesterol accumulates in
smooth muscle cells and macrophages in the intima of arteries
– In hereditary hyperlipemia, cholesterol accumulates in macrophages, usually under the skin, forming tumor-like structures known as xanthomas
![Page 24: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/24.jpg)
![Page 25: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/25.jpg)
![Page 26: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/26.jpg)
![Page 27: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/27.jpg)
Intracellular Accumulation of Proteins
![Page 28: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/28.jpg)
Excesses exceeding
capacity of cell to metabolize
Defects in protein folding, rendering them vulnerable to intracellular aggregation:
Synthesis and secretion of excessive
protein
Nephrotic syndrome, defined by 24 hr. urine protein > 3.5 gms.
manifested as cytoplasmic protein droplets in renal tubular epithelium
Monoclonal immunoglobulins in serum and/or urine, due to bone marrow containing excess numbers of neoplastic plasma cellsEg: Myeloma
Inherited metabolic disease, PiZZ genotype (1/7000 persons), resulting in < 10% normal plasma levels of alpha 1 - antitrypsin with accumulations of protein in hepatocytes
![Page 29: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/29.jpg)
Intracellular Accumulation of Proteins
• Primarily in epithelial cells of the proximal convoluted tubules of the kidney and in plasma cells
• In the kidney, this excessive accumulation occurs subsequent to leakage of proteins from glomeruli into the glomerular filtrate
• Plasma cells – RUSSEL BODIES
• Alpha 1 antitrypsin deficiency
• Mallory body or alcholic hyalin
![Page 30: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/30.jpg)
![Page 31: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/31.jpg)
![Page 32: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/32.jpg)
Intracellular Accumulation of Glycogen
• Glycogen Infiltration and Glycogen Storage
• Glycogen appears as clear vacuoles in the cytoplasm of cells
• Hyperglycemia
• Epithelial cells of the distal portion of the proximal convoluted tubule and in the loop of Henle in the kidney
• Leukocytes within inflamed or necrotic tissue
• Liver • Cardiac muscle fibers
![Page 33: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/33.jpg)
Intra cellular accumulations
Pigments
![Page 34: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/34.jpg)
• Pigments are colored substances, some of which are normal constituents of cells (e.g., melanin), whereas others are abnormal and accumulate in cells only under special circumstances – Exogenous– Endogenous
![Page 35: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/35.jpg)
EXOGENOUS ENDOGENOUS
1. Carbon – coal dust• Anthracosis• Coal workers
pneumoconiosis
2. Tattooing • India ink, carbon
3. Ingested • Argyria : silver • Lead • carotenemia
1. Lipofuschin
2. Melanin
3. Hemosiderin
![Page 36: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/36.jpg)
• Exogenous pigments Carbon (anthracosis) Coal dust (pneumoconiosis) Lung: pick up by alveolar macrophages
regional lymph nods
blackening the tissues of the lungs (anthracosis)
![Page 37: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/37.jpg)
Here is anthracotic pigment in macrophages in a hilar lymph node
The black streaks seen between lobules of lung beneath the pleural surface are due to accumulation of anthracotic pigment.
![Page 38: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/38.jpg)
EXOGENOUS ENDOGENOUS
1. Carbon – coal dust• Anthracosis• Coal workers
pneumoconiosis
2. Tattooing • India ink, carbon
3. Ingested • Argyria : silver • Lead • carotenemia
Melanin
Hemosiderin
Lipofuschin
![Page 39: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/39.jpg)
Lipofuschin • Insoluble pigment, also known as lipochrome or
wear-and-tear pigment • Composed of polymers of lipids and phospholipids
in complex with protein
• Not injurious to the cell or its functions • Telltale sign of free radical injury and lipid
peroxidation
![Page 40: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/40.jpg)
• In sections it appears as a yellow-brown, finely granular cytoplasmic, often perinuclear, pigment
• Seen in liver and heart of ageing patients• Patients with severe malnutrition• Cancer cachexia
![Page 41: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/41.jpg)
![Page 42: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/42.jpg)
![Page 43: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/43.jpg)
![Page 44: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/44.jpg)
![Page 45: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/45.jpg)
![Page 46: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/46.jpg)
EXOGENOUS ENDOGENOUS
1. Carbon – coal dust• Anthracosis• Coal workers
pneumoconiosis
2. Tattooing • India ink, carbon
3. Ingested • Argyria : silver • Lead • carotenemia
• Lipofuschin
• Melanin
• Hemosiderin
![Page 47: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/47.jpg)
Melanin • Endogenous, non-hemoglobin-derived, brown-black
pigment
• Only endogenous brown-black pigment
• Formed when the enzyme tyrosinase catalyzes the oxidation of tyrosine to dihydroxyphenylalanine in melanocytes and dendritic cells.
![Page 48: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/48.jpg)
DISORDERS OF MELANIN PIGMENTATION
HYPERPIGMENTATION
HYPOPIGMENTATION
![Page 49: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/49.jpg)
HYPERPIGMENTATION
GENERALISED LOCALISED
1. Addisons disease2. Chloasma
1. Café au lait spots2. Peutz jeghers
syndrome3. Melanosis coli4. Nevi and tumors
![Page 50: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/50.jpg)
HYPOPIGMENTATION
GENERALISED LOCALISED
Albinism Vitiligo
![Page 51: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/51.jpg)
EXOGENOUS ENDOGENOUS
1. Carbon – coal dust• Anthracosis• Coal workers
pneumoconiosis
2. Tattooing • India ink, carbon
3. Ingested • Argyria : silver • Lead • carotenemia
• Lipofuschin
• Melanin
• Hemosiderin
![Page 52: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/52.jpg)
![Page 53: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/53.jpg)
Hemosiderin• Hemoglobin-derived, golden yellow-to-brown,
granular or crystalline pigment • Major storage forms of iron • Hemosiderin pigment represents aggregates of ferritin
micelles
• Small amounts of hemosiderin can be seen in the mononuclear phagocytes of the bone marrow, spleen, and liver, which are actively engaged in red cell breakdown.
![Page 54: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/54.jpg)
Excess of iron
LOCAL SYSTEMIC
Common bruise 1. Acquired Hemosiderosis
• Hemolytic disorders• Blood transfusion• Iatrogenic
2. Heriditary hemochromatosis• Increased
absorption3. Excessive dietary intake.
![Page 55: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/55.jpg)
![Page 56: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/56.jpg)
Iron pigment appears as a coarse, golden, granular pigment lying within the cell's cytoplasm
![Page 57: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/57.jpg)
Perls prussian blue stain
![Page 58: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/58.jpg)
![Page 59: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/59.jpg)
The brown coarsely granular material in macrophages in this alveolus is hemosiderin that has accumulated as a result of the breakdown of RBC's and release of the iron in heme. The macrophages clear up this debris, which is eventually recycled.
![Page 60: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/60.jpg)
![Page 61: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/61.jpg)
EXOGENOUS ENDOGENOUS
1. Carbon – coal dust• Anthracosis• Coal workers
pneumoconiosis
2. Tattooing • India ink, carbon
3. Ingested • Argyria : silver • Lead • carotenemia
1. Lipofuschin
2. Melanin
3. Hemosiderin
![Page 62: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/62.jpg)
Summary
• Intracellular accumulations
– Fatty change– Proteins– Carbohydrates– pigments
![Page 63: Cell injury : Intracellular accumulations](https://reader034.vdocument.in/reader034/viewer/2022042706/58742c871a28ab72188b6aa7/html5/thumbnails/63.jpg)
Thank you.