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Questions and Answers
What is the most common form of lipid accumulation in fatty change?
Which of the following conditions is commonly associated with fatty liver?
Which mechanism contributes to the development of fatty liver?
What is a major cause of fatty liver associated with alcohol?
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Which organ is primarily affected by fatty change?
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Which condition might lead to irreversible cell injury in fatty change?
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In the context of fatty change, what role do hepatotoxins play?
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What happens when the capacity of the liver to metabolize fat is exceeded?
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Which of the following substances can accumulate within cells?
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What is NOT a pathway of abnormal intracellular accumulations?
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Which condition is an example of fatty liver?
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Which type of intracellular accumulation includes exogenous substances?
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What causes a deficiency in critical enzymes that can lead to storage diseases?
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Which of the following describes the result of abnormal metabolism leading to intracellular accumulation?
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Which of the following situations may lead to the inability to degrade phagocytosed particles?
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What is hydropic change in the context of intracellular accumulation?
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What is a prominent microscopic feature of fatty liver disease?
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Which condition is associated with an accumulation of cholesterol and cholesteryl esters in macrophages?
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What causes an increase in the yellow, greasy appearance of the liver in fatty liver disease?
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What is the main function of cholesterol in the body?
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What microscopic preparation is used to distinguish lipid accumulations in the liver?
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Which of the following is NOT a cause of lipid accumulation in the liver?
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What is a characteristic feature of atherosclerotic plaques in arteries?
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Which cells become overloaded with lipids during certain pathological processes?
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Study Notes
Intracellular Accumulations
- Cells may accumulate abnormal amounts of various substances, which may be harmless or associated with varying degrees of injury.
- Substances may be located in the cytoplasm, organelles (typically lysosomes), or the nucleus.
- Substances may be synthesized by the affected cells or produced elsewhere.
Pathways of Abnormal Intracellular Accumulations:
- Abnormal metabolism: A normal substance is produced at a normal or increased rate, but metabolic rate is inadequate to remove it (e.g., fatty change in the liver).
- Alterations in protein folding and transport: A normal or abnormal endogenous substance accumulates due to genetic or acquired defects in folding, packaging, transport, or secretion. Mutations leading to defective folding and transport can cause protein accumulation (e.g., α1-antitrypsin deficiency).
- Deficiency of critical enzymes: An inherited defect in an enzyme may result in the failure to degrade a metabolite. These disorders are called storage diseases.
- Inability to degrade phagocytosed particles: An abnormal exogenous substance is deposited and accumulates because cells lack the enzymatic machinery to degrade it or the ability to transport it to other sites (e.g., accumulations of carbon or silica particles).
Intracellular Accumulations Include:
- Hydropic change (water).
- Fatty change: Any abnormal accumulation of triglycerides within parenchymal cells.
- Proteins: Abnormal protein accumulation is often irreversible.
- Glycogen: Glycogen storage diseases.
- Complex carbohydrates: Mucopolysaccharidoses and other complex carbohydrate diseases.
- Minerals: Iron, as hemosiderin, or carbon, as anthracotic pigment.
- Pigments.
- Calcium.
- Amyloid.
Lipids
- Triglycerides are the most common form of lipid accumulation.
- Cholesterol and cholesterol esters are also found.
Fatty Change (Steatosis)
- Refers to any abnormal accumulation of triglycerides within parenchymal cells.
- Caused by an imbalance between the uptake, utilization, and secretion of fat.
- Defects in fat metabolism are often induced by alcohol consumption, and also associated with diabetes, obesity, and toxins.
- Commonly seen in the liver.
- May also occur in the heart, kidney, skeletal muscle and other organs.
- Depending on the cause and amount of accumulation, fatty change may be mild and reversible or severe, producing irreversible cell injury and cell death.
Conditions with Excess Fat:
- Obesity
- Diabetes mellitus
- Congenital hyperlipidemia: Conditions with excess fat exceeding the capacity of the liver to metabolize it.
- Liver cell damage, when fat cannot be metabolized in it.
Fatty Liver
- Most common cause: Alcohol abuse
- Free fatty acids are esterified in the liver to triglycerides and are converted into cholesterol/phospholipids or oxidized to ketone bodies.
- Triglycerides + Apoproteins = Lipoproteins
- Fatty change in the liver is reversible, but when excessive it may lead to cirrhosis.
Major Causes of Fatty Liver
- Alcoholic liver disease (most common)
- Protein malnutrition (starvation)
- Diabetes Mellitus
- Obesity
- Hepatotoxins
- Hypoxia (anemia, cardiac failure)
- Drugs
Mechanisms of Fatty Liver
- Excessive entry of free fatty acids into the liver (e.g., starvation).
- Enhanced fatty acid synthesis.
- Decreased catabolism of triglycerides (↓ fatty acid oxidation).
- Increased esterification of fatty acids to triglycerides as a result of an increase in α-glycerophosphate (alcohol).
- Decreased apoprotein synthesis (carbon tetrachloride poisoning).
- Impaired lipoprotein secretion from the liver (e.g., alcohol).
- Starvation will increase this.
- Hepatotoxins (e.g., alcohol) by disrupting mitochondria and SER; anoxia
- CCl4 and protein malnutrition
- Defects in any of the steps of uptake, catabolism, or secretion can lead to lipid accumulation.
Morphology of Fatty Liver
- Grossly: Enlarged, yellow and/or greasy. Note/Gross morphology in the liver depends on severity. Increased size is observed, and the liver becomes yellow and greasy when severe.
- Microscopically: Fat is seen as small, fatty, cytoplasmic droplets or as large vacuoles. Fat vacuoles displace the nucleus to the periphery of the cell. Vacuoles appear clear, with well-defined edges.
- Note/Lipid accumulations must be distinguished from accumulations of water or glycogen, using special preparation and stain – Oil Red-O.
Cholesterol and Cholesterol Esters
- Cholesterol is used for the synthesis of cell membranes.
- Cellular cholesterol metabolism is tightly regulated to ensure normal cell membrane synthesis without significant intracellular accumulation.
- However, phagocytic cells may become overloaded with lipid (triglycerides, cholesterol, and cholesteryl esters) in several different pathologic processes.
- Cholesterol & esters accumulate in macrophages (foam cells) and foreign body giant cells.
- Accumulations of cholesterol are manifested by intracellular vacuoles.
Conditions Associated with Cholesterol and Cholesterol Esters Accumulation:
- Atherosclerosis
- Acquired and hereditary hyperlipidemia
- Inflammation and necrosis
Atherosclerosis
- Smooth muscle cells and macrophages are filled with lipid vacuoles composed of cholesterol and cholesteryl esters in the wall of arteries.
- These give atherosclerotic plaques their characteristic yellow color and contribute to the pathogenesis of the lesion.
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Description
This quiz explores the mechanisms and pathways of intracellular accumulations in cells. Participants will learn about abnormal metabolism, protein transport issues, and enzyme deficiencies that can lead to harmful substances accumulating within cells. Assess your understanding of cellular processes and their implications for health and disease.
