Exam #1: Cellular Adaptations and Accumulations II Flashcards
Review the process of lysosomal catabolism.
- Primary lysosomes bud from the golgi apparatus
- These organelles are filled with hydrolytic enzymes
- A primary lysosome will fuse with a phagocytic vesicle derived from invaginated plasma membrane to form a secondary lysosome
What is a primary lysosome?
Small membrane found vesicle that buds from the Golgi apparatus
What is a secondary lysosome?
- A primary lysosome that has fused with a phagocytic vesicle derived from invaginated plasma membrane
- Also called a phagolysosome
What is heterophagy?
Materials from extracellular environment taken up through endocytosis
- Large= phagocytosis
- Small= pinocytosis
What is autophagy?
Lysosomal digestion of cell’s down components; common in removal of senescent/damaged organelles & cellular remodeling association with cell differentation
What are residual bodies?
Some lipids and other materials remain undigested in cells e.g. lipofuscin that is known as the “aging pigment”
What are Hereditary Lyosomal Storage Disorders?
Abnormal accumulations of intermediate metabolites in lysosomes
*Note that drugs can disrupt the function of lysosome as well
What happens in the p450 system?
Smooth ER is involved in metabolism of various chemicals/ compounds; synthesizes phospholipids & detox
- SER undergoes hypertrophy as adaptive response to drug abuse, esp. barbiturates
E.g. Barbituates & p450 mixed function oxidasde system
What mitochondiral alterations are seen in alcoholic liver disease?
- Alcoholic liver disease can induce mitochondrial hypertrophy called “megalomitochondria”
What is the cytoskeleton? What are the different functions of the components of the cytoskeleton?
- Thin filaments= movement & phagocytosis
- Microtubules= motility, phagocytosis, and mitotic spindle formation for mitotic spindle
- Intermediate filaments= intracellular scaffold, maintain cellular architecture–can accumulate and be pathologic e.g. Alzheimer’s Disease
What are cytoskeletal proteins?
- Proteins of the cytoskeleton that are linked to cellular receptors
- These play an important role not only in membrane permeability, but also in how the cell functions
E.g. cytoskeletal proteins are active participants in signal transduction & lymphocyte receptors for antigens
What are intracellular accumulations manifestations of?
Metabolic derangement–this is a storage of some product that cannot be degraded
What are the three categories of intracellular accumulations?
1) Normal endogenous substances–produced at a normal or increased rate but the metabolism is inadequate to remove it
2) Normal or abnormal endogenous substance accumulates secondary to genetic of acquired defects in metabolism
3) Abnormal exogenous substance that cannot be removed
What are the mechanisms that lead to intracellular accumulations?
1) Abnormal metabolism e.g. fatty liver (fat accumulates in vesicles within the cell)
2) Alterations in protein folding and transport
3) Deficiency of critical enzymes leading to accumulation of an insoluble intermediate
4) Inability to degrade phagocytosed particles
Give an example of abnormal metabolism leading to intracellular accumulations.
Fatty Liver Disease
- Fatty acids enter the cell & the liver can’t keep up
What is steatosis?
Abnormal accumulations of triglycerides within parenchymal cells
- Yellow discoloration
- Caused by toxins, protein malnutrition, obesity, DM, and alcohol
*This leads to cirrhosis
Review fatty acid metabolism and the mechanism leading to accumulation of triglycerides.
A defect in any step of metabolism causes an accumulation of triglycerides
What is athersclerosis?
Plaques, smooth muscle cells & macrophages form within intimal layer of aorta & large arteries fill with lipid vacuoles
- Lipid vacuoles= foam cell
- Aggregates produce yellow, cholesterol laden atheromas
What is a cholesterol cleft?
Some foam cells rupture, releasing lipids in the extracellular space–>crystalize
What are xanthomas? What patient population are they often seen in?
- Yellow discoloring accumulations around the eyes
- Foam cells
- Seen in familial hypercholesterolemia
What is cholesterolosis of the gallbladder?
Foam cells in the gallbladder
What causes protein accumulations?
- Point mutations interrupt protein folding and transport
- Accumulation occurs within vesicles
Specifically, there are diverse causes of protein accumulation e.g. reabsorption droplets in proteinuria
How do protein accumulations appear?
Protein accumulations form a pink “hyaline” material in the cytoplasm
*Note that these are less common than lipid accumulations
What can Nephrotic Syndrome lead to?
Nephrotic syndrome is a group of symptoms that include protein in the urine, low blood protein levels, high cholesterol levels, high triglyceride levels, and swelling.
- This syndrome will lead to the reabsorption of protein droplets in the proximal renal tubule
What are russel bodies?
- Synthesis of excessive amounts of normal proteins can occur
- One example is plasma cells that produce antibodies
- Antibodies can accumulate in the plasma cell, which is referred to as a “Russel Body”
Thus, this is not always a pathologic process
What are mallory bodies?
In alcoholic liver disease, cell injury leads to a congregation of protein & keratin intermediate filament that stains very pink
- These are called “Mallory Bodies” or alcoholic hyalin
What is the function of chaperon proteins?
- Chaperones aid in proper folding & transport of proteins
- Repair misfolded proteins
- Facilitate degradation of damaged proteins by “flagging” them with ubiquitin
What is alpha-1 antitrypsin deficiency?
- Alpha-1 antitrypsin is produced by the liver; it degrades trypsin
- When deficient, there is an accumulation of this protein in the liver
- Trypsin levels increase & can lead to the development of emphysema
- Trypsin can also increase in liver, leading to cirrhosis
What class of diseases does ER stress play a major role in?
Neurodegnerative disease
What is amyloidosis?
Toxic, aggregated, abnormally folded protein that stains orang-red with Congo red staining
What is a hyaline change?
Descriptive term for non-specific morphological changes that appear pink under H & E stain
When there are abnormalities of metabolism of glucose or glycogen, how do excessive intracellular deposits appear on microscopy?
Clear
In DM, where can glycogen be seen?
- Cytoplasm or renal tubular epithelium
- Hepatocytes
- Cardiac monocytes
- B-cells of Islets of Langerhans
What are glycogen storage diseases?
A class genetic enzymatic defects in synthesis or breakdown of glycogen that leads to a massive stockpiling that leads to cell injury and cell death
What is glycogen storage disease type II?
Pompe’s disease
- Acid alpha glyocsidase deficiency that effects the heart
What is the most common exogenous pigment that is accumulated in the body?
Carbon i.e. coal dust that is picked up by macrophages
What is anthracosis?
Darkening of lymph nodes from the accumulation of macrophages containing carbon pollution
What is coal worker’s penumoconiosis?
Heavy accumulations of coal dust i.e. carbon that leads to emphysema or fibroelastic reaction; a restrictive lung disease seen in coal miners
What is tatooing in a pathologic sense?
Accumulation of exogenous pigmentation in the skin, specifically, in dermal macrophages
What is lipofuscin?
- Lipofuscin is a brownish-yellow, granular intracellular material that is called the “wear and tear pigment, of the aging pigment”
- It is difficult to breakdown lipids and phospholipids that leads to the formation of “Lipochrome”
What is melanin? What is the function of melanin?
Brown pigment in the skin that protects from UV raidation
What is hemosiderin?
- Gold-yellow-to-brown pigment that forms from excess iron locally or systemically
- Represents aggregates of ferritin micelles
*Heart failure cells
What is hemosiderosis?
Systemic overload of iron i.e. deposition of iron in many organs and tissues
