INTRACELLULAR ACCUMULATIONS

• Accumulation of abnormal amounts of various substances due to manifestations of metabolic derangements of the cell

INTRACELLULAR ACCUMULATIONS

NORMAL CELLULAR COMPONENTS

lipid, carbohydrates

ABNORMAL SUBSTANCES

Endogenous and Exogenous

SITES• Cytoplasm (phagolysosomes)• Nucleus

MECHANISM OF ACCUMULATIONS

• Due to overproduction

• Due to inadequate metabolism

• Lack of enzyme machinery to remove

Normal substance produced at normal or increase rate

Metabolism is inadequate to remove it

Accumulation

Fatty change in liver

Mutated gene

Abnormal protein folding

Inability to degrade abnormal protein

AccumulationAlpha 1 antitrypsin

def.

Normal endogenous substance

Enzyme Deficiency

Metabolite Accumulation

Storage disorders

Exogenous substance

No enzymatic machinery for its degradation or transport

AccumulationAccumulation of carbon in lungs

ACCUMULATION OF LIPIDS

Normal lipid metabolism Free fatty acids from adipose tissue or ingested food

Transported to hepatocytes

Esterified Converted to Oxidized to

Triglycerides Cholesterol or phospholipids Ketone bodies

STEATOSIS OR FATTY CHANGE• Abnormal accumulation of triglycerides in liver

parenchyma

Alcohol Toxin and Malnutrition Hypoxia Starvation

Mitochondria Apoproteins Inhibit oxidation Mobilization

Accumulation of lipids

Fatty change or steatosis

FATTY CHANGE - LIVERGrossly • Liver enlarges, become increasingly yellow, soft and greasy.

Microscopically • Small vacuoles in cytoplasm around the nucleus• Vacuoles coalesce displacing the nucleus to periphery• Occasionally fatty cysts are formed

FATTY CHANGE - HEART• Occurs due to prolonged moderate hypoxia as in

anemia• In case of infectious myocarditis like of diphtheria.

Grossly• Bands of yellow myocardium alternating with bands of

darker red brown uninvolved myocardium• Tigered effect

Microscopically • Intracellular deposits of fat

CHOLESTEROL AND CHOLESTEROL ESTERS

• Atheromatous plaque

• Cholesterolosis

Xanthomas

PROTEINIntracellular accumulation of protein usually appear as • Round eosinophilic droplets,• Vacuoles or• Aggregatesin cytoplasm

Alhpa 1 antitrypsin def

GLYCOGEN• It’s a readily available energy source in cytoplasm of

cells• Excessive intracellular accumulation occurs in

abnormal glucose or glycogen metabolism• DM (renal tubular epithelial cells, liver, beta cells,

heart muscles)• Glycogen storage disorders

Angiokeratoma corporis diffusum (Fabry's disease)

EWINGS SARCOMA

PIGMENT

• Exogenous• Endogenous

Exogenous• Most common is carbon (coal dust).• Common air pollutant.• Inhaled by macrophages within alveoli • Leads to Anthracosis (blackening of lungs)• Severe accumulation like in coal miners leads to coal

worker’s pneumoconiosis

Pneumoconiosis• Silicosis – Silica dust, stone and sandblasters• Asbestosis – Asbestos dust in shipbuilding workers• Byssinosis – Cotton dust

EndogenousLipofuscin

• Lipochrome or wear and tear pigment

• Derived through lipid peroxidation of polyunsaturated lipids of

membranes

• Telltale sign of lipid peroxidation and free radical injury

• In sections appears as yellow brown, finely granular, cytoplasmic,

often perinuclear pigment

• Seen in cells undergoing slow regressive changes as in liver and heart of aging patients or patient with severe malnutrition or cachexia.

Other pigmentsMelaninHemosiderinBilirubin