Pathology

Dr.Ban Lecture (7)

Intracellular accumulations

Definition: abnormal accumulation of some products within the cell is a manifestation of metabolic
derangement of cells.

Three categories of substances:

1- Normal cellular constituent :-

Water, lipids, proteins, carbohydrates.

2- Abnormal substance

- Exogenous: ex. Mineral

- Endogenous: product of abnormal metabolism

3- Pigments

Lipid Accumulations

Accumulations of:

1- Triglycerides
- Fatty change (seen in alcoholics)
2- Cholesterol
- Atherosclerosis
- Xanthomas
- Cholesterolosis

Fatty Change (Steatosis)

- It is abnormal accumulation of triglycerides in parenchymal cells.

- Organs affected:-
1- Liver (most common).
2- Heart, muscles and kidneys.

Mechanism of fatty change:-

Free fatty acids from adipose tissue or ingested food are normally transported into hepatocytes.
In the liver, they are esterified to triglycerides, converted into cholesterol or phospholipids, or
oxidized to ketone bodies. Release of triglycerides from the hepatocytes requires apoproteins

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to form lipoproteins. Excess accumulation of triglycerides within the liver may result from defects
in any one of the events in the sequence from fatty acid entry to lipoprotein exit.

Causes of fatty change of the liver

1 - Alcohol is the MCC (most common cause) of fatty change in the liver: alter mitochondrial and
SER function and thus inhibit fatty acid oxidation

2- Anoxia inhibits fatty acid oxidation

3- Starvation increases fatty acid mobilization from peripheral stores

4- CCl4 and Kwashiorkor (Decreased Protein intake) decrease the synthesis of apoproteins

5- Diabetes Mellitus

6- obesity

Morphology of fatty change of Liver

- Gross: normal size or enlarged liver with a yellowish discoloration.

- Microscopically:
- Clear spaces (vacuoles) in the cytoplasm pushing the nucleus of the hepatocytes to the
periphery.
- Special stains: Sudan IV and Oil Red O (orange red color to lipid).

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Cholesterol and Cholesterol Esters

- Cells use cholesterol for synthesis of cell membrane.

- Accumulation of cholesterol seen in many pathological conditions:
1- Atherosclerosis (will be taught in CVS)
2- Xanthomas
3- Cholesterolosis

Xanthomas

- Tumor-like masses composed of Clusters of macrophages (foamy cells) containing cholesterol.

- Occur in the Subepithelial connective tissue of skin & in tendons.
- Seen in hereditary hyperlipedemic states.

Cholesterolosis

- Refers to focal accumulation of cholesterol laden macrophages in the lamina propria of the
gallbladder.

Hyaline change

 Non-specific term used to describe any intracellular or extracellular accumulation that has a
pink homogenous appearance.
 Most commonly occurs due to accumulation of proteinaceous material (protein
accumulation).
 ccumulation can be:

1- Intracellular hyaline
- Protein within proximal tubule of kidney.
- Russell bodies.
- Mallory Alcoholic hyaline.
2- Extracellular hyaline
- Collagen in old scars
- Amyloid

Resorption protein droplets

- Most commonly seen in proximal renal tubular cells.

- In patients with protein loss in the urine (proteinuria) Ex Nephrotic syndrome

Russell Body

- Excess immunoglobulin accumulation in RER of plasma cells.

- Fuse to form eosinophilic globules known as Russell bodies.

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Mallory bodies (=Alcoholic Hyaline)

- Are masses of keratin intermediate filaments within hepatocytes.

- Seen in patients with alcoholic liver disease.

Hyaline arteriolosclerosis

Refers to arterioles that have a glassy, amorphous eosinophilic material in the vessel wall that
often narrows the lumen seen in small vessels in DM and hypertension.

Pigment Accumulations

Pigments are colored substances.

1- Exogenous: from outside the body

- Carbon / coal dust
- Tattoo ink
2- Endogenous: synthesized within the body
- Lipofuscin
- Melanin
- Bilirubin
- Hemosiderin

Carbon or coal dust

 Anthracotic pigment:-
- Air pollution Inhalation of carbon dust  alveolar macrophages  accumulation in
lymphatics, regional lymph nodes and lungs  blacken the tissues of the lungs (anthracosis)
and the involved lymph nodes.
 Coal dust: -
- In Coal miners accumulation of coal dust composed of carbon and silica induces
fibroblastic reaction  lung disease = coal worker’s pneumoconiosis.
 Tattooing
- Localized pigmentation of skin. Pigments  phagocytosed by dermal macrophages.

Endogenous pigments

- Lipofuscin: (Latin: fuscus = brown)

- Also known as Lipochrome, wear and tear or aging pigment.
- Is an end-product of membrane lipid peroxidation.
- Not injurious to cell.
- Sign of free radical injury and lipid peroxidation.
- Appearance: yellow brown, finely granular, intracytoplasmic, often perinuclear.

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- Seen in liver and heart of
1- Aging patients.
2- Patients with malnutrition or cancer cachexia.

Melanin

- A brown black pigment

- Tyrosinase catalyses the oxidation of tyrosine into Dihydroxyphenylalanine (DOPA) in the
melanosomes
- Synthesized in melanocytes within the epidermis.
- Sunlight and ACTH stimulate melanin synthesis in the skin.

Melanin excess

1.Conditions associated with an increase in ACTH:

- Functioning pituitary adenoma

- Ectopic ACTH

- Addison’s disease (destruction of adrenal gland):-

All associated with increased skin pigmentation.

2. Nevocellular nevi or moles: Benign proliferation of nevus cells which are modified
melanocytes.

3.Malignant melanoma: A malignant tumor of melanocytes.

Absence of Melanin

Albinism

- Characterized by absence of tyrosinase.

- Melanocytes are present but do not contain melanin within melanosomes.

Vitiligo

- Autoimmune destruction of melanocytes produces patchy areas of depigmentation.