Intracellular AccumulationsIntracellular Accumulations

• Manifestation of “metabolic derangements”

:intracellular accumulation of abnormal amounts of various substances

Fat

Protein

Glycogen

Pigments

Mechanisms of Mechanisms of intracellular intracellular

accumulationsaccumulations

(1)(1) abnormal metabolism abnormal metabolism

(2)(2) alterations in protein alterations in protein folding and transportfolding and transport

(3)(3) deficiency of critical deficiency of critical enzymesenzymes

(4)(4) inability to degrade inability to degrade phagocytosed particlesphagocytosed particles

Intracellular Accumulations of Intracellular Accumulations of LipidsLipids

• Accumulation of Lipids - Triglycerides - Cholesterol

• Steatosis (fatty change) : abnormal accumulation of triglycerides

within parenchymal cells(especially hepatocytes)

– fatty liver in chronic alcoholism,

Diagram of the possible mechanisms leading to accumulation of triglycerides in fatty liver. Any defects in any of the steps of uptake,catabolism,or secretion can result in lipid accumulation.

• Excessive entry of free fatty acids into the liver (starvation,obesity).• Metabolic disease (Diabetes mellitus) .• Decreased fatty acid oxidation (hypoxia).• Increased esterification of fatty acid to triglycerides (alcohol).• Decreased apoprotein synthesis (CCl4

&protein malnutrition).• Impaired lipoprotein secretion from the liver (alcohol).

FATTY CHANGE

LIPID LAWLIPID LAW• ALL Lipids are YELLOW

grossly and WASHED out (CLEAR) microscopically

•Special stains

Sudan IV, Oil red O,

•Liver

•Heart

•Kidney

FATTY LIVERFATTY LIVER

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 19 October 2005 05:51 PM)

© 2005 Elsevier

Fatty liverFatty liver

Liver: Fatty change

Intracellular Accumulations Intracellular Accumulations of of LipidsLipids

• Cholesterol and Cholesterol Esters :Atherosclerosis - accumulation of cholesterol in

macrophage (foam cell) and smooth muscle cells in the intima of aorta and arteries

:Cholesterolosis - accumulation of foam cells in the

lamina propria of gallbladder

Cholesterolosis. Cholesterol- laden macrophages (foam cells) from a focus of gall bladder cholesterolosis(arrow).

Intracellular Accumulations of Intracellular Accumulations of ProteinsProteins

• ((LM→ eosinophilic glassy hyaline LM→ eosinophilic glassy hyaline changes):-changes):-

• Accumulation of protein droplets in proximal renal tubule in renal disease with heavy protein leakage across the glomerular filter (Nephrotic syndrome)

• Absorption of protein causing hyaline Absorption of protein causing hyaline

droplets in proximal epithelial cells indroplets in proximal epithelial cells in

the kidney.the kidney.

Protein reabsorption droplets in the renal tubular epithelium.

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 19 October 2005 05:51 PM)

© 2005 Elsevier

•Masses of altered intermediate filaments Masses of altered intermediate filaments (eg. Mallory bodies in alcoholic liver).(eg. Mallory bodies in alcoholic liver).Cytoskeleton composed of several proteins:-Cytoskeleton composed of several proteins:-1.Microtubules1.Microtubules2.Thin actin2.Thin actin3.Thick myosin.3.Thick myosin.4. Intermediate filaments (flexible scaffold)4. Intermediate filaments (flexible scaffold) - keratin in epithelial cells.- keratin in epithelial cells. - desmin in muscle cell.- desmin in muscle cell. - vimentin in connective tissue cell.- vimentin in connective tissue cell. - neurofilaments in neurons.- neurofilaments in neurons. - glial filaments in astrocytes.- glial filaments in astrocytes.

Mallory bodies (the red globular material) composed of intermediate keratin

filaments in liver cells

Russel bodies in plasma cells

• Russell bodies in plasma cells in chronic Russell bodies in plasma cells in chronic inflammatory diseasesinflammatory diseases..

Russell bodies in plasma cell(EM)

Intracellular Accumulations of Intracellular Accumulations of ProteinsProteins

• Defects in protein folding

:Defective intracellular transport and secretion

:ER stress induced by unfolded and misfolded protein – cell death

Eg :Aggregation of abnormal folded protein - amyloidosis

“Patients with abnormal metabolism of glucose or glycogen”

LM:- clear vacuole (PAS= Periodic acid shiff reagent- pink violet in colour)

• Diabetes mellitus :disorder of glucose metabolism - glycogen accumulate in epithelial cells

of renal tubules, liver cells, beta-cells of the islets of Langerhans and heart muscle cells

Intracellular Accumulations of Intracellular Accumulations of GlycogenGlycogen

• Glycogen storage disease (Glycogenosis)

- genetic diseases

- defect of enzymes in the synthesis or breakdown of glycogen

accumulation cell injury death

Intracellular Accumulations of Intracellular Accumulations of GlycogenGlycogen