RR 01 Cell Injury Part 3

Cytosolic acumulation of trigluceride
-Packaged in VLDL fraction

1. Occurs with increased conversion of dihydroxyacetone phosphate (DHAP), an intermediate of glycolysis, to glycerol 3-phosphate (G3-P)
-Addition of 3 fatty acids to G3-P produces TG in the liver
-Increased production of NADH from alcohol metabolism accelerated conversion of DHAP to G3-P
2. Occurs with increased production of DHAP, which increases G3-P, which increases TG
-Increased intake of carbohydrates (eg kwashiorkor)
3. Increased availability of FAs increases synthesis of TG from G3-P

1. Increased synthesis of FAs from acetyl CoA
-Acetyl CoA is the end-product of alcohol metabolism
2. Increased mobilization of FAs from TG stores in adipose tissue by activation of hormone sensitive lipase
-Causes include alcohol and starvation
3. Decreased beta-oxidation of FAs int he mitochondrial matrix
-Causes include alcohol and diphtheria toxin, which produce mitochondrial dysfunction

1. Increased synthesis of triglyceride
2. Decreased packaging of TG into VLDL and secretion of VLDL into plasma by apolipoprotein B-100
-Example: decreased protein intake leading to decreased synthesis of apolipoprotien B-100 (eg kwashiokor)

1. Normal or enlarged liver with yellowing discoloration
2. Clear space pushing the nucleus to the periphery

1. Causes:
a. Severe anemia
b. Diphtheria
-Exotoxin inhibits beta-oxidation of FAs
2. Heart has miottled appearance
-Tabby cat heart, thrush heart

1. Major soluble iron storage product
2. Synthesized and stored in bone marrow macrophages and hepatocytes
3. Small amounts circulate in serum
-Directly correlates with ferritin stores in the bone marrow

1. Insoluble product of ferritin degradation in lysosomes
2. Does not circulate in serum
3. Appears as golden brown granules in tissue
4. Appears as blue granules when stained with Prussian blue

1. Deposition of calcium phosphate in necrotic tissue
2. Normal serum calcium and phosphate
3. Examples
a. Calcification in chronic pancreatitis
b. Calcified atherosclerotic plaque
c. Periventricular calcification in congenital cytomegalovirus infection

1. Depositon of calcium phosphate in normal tissue
2. Due to increased serum calcium and/or phosphate
a. Causes of hypercalcemia - primary hyperparathyroidism, malignany-induced hypercalcemia
b. Causes of hyperphosphatemia - renal failure, primary hypoparathyroidism
-Excess phosphate drives calcium into normal tissue
3. Examples:
a. Calcification of renal tubular basement membranes in the collecting ducts (nephrocalcinosis)
-This can produce nephrogenic diabetes insipidus and renal failure
b. Basal ganglia calcification in hypoparathyroidism

Decrease in size and weight of a tissue or organ

1. Decreased hormone stimulation
-Hypopituitarism causing atrophy of target organs
2. Decreased innervation
3. Decreased blood flow
4. Decreased nutrients
5. Increased pressure
-Atrophy or renal cortex and medulla in hydronephrosis
-Thick pancreatic duct secretions in cystic fibrosis occlude the lumens causing increased luminal back-pressure and compression atrophy of the exocrine glands and tubular epithelium

1. Shrinkage of cells due to increased catabolism of cell organelles (eg mitochondria)
a. Organelles and cytosole form autophagic vacuoles
b. Autophagic vacuoles fuse with primary lysosomes for enzymatic degradation
c. Undifested lipids are stoed as residual bodies (lipofuscin)
2. Loss of cells by apoptosis

-Tissue discoloration that results from lysosomal accumulation of lipofuscin ("wear and tear" pigment).
-Lipofiuscin is an indigestible lipid derived from lipid peroxidation of cell membranes, which may occur in atrophy and free radical damage of tissue

Increase in cell size

1. Increased work load
a. Left venticular hypertrophy in response to an increase in afterload or preload
b. Skeletal muscle hypertrophy in weight training
c. Smooth muscle hypertrophy in the urinary bladder in response to urethral obstruction
d. Surgical removal of one kidney with compensatory hypertrophy of the other
2. Cell enlargement in CMV infections

1. Induction of genes for synthesis of growth factors, nuclear transcription, and contractile proteins
2. Increase in cytosol, number of cytoplasmic organelles, and DNA content

Increase in the number of normal cells

1. Hormone stimulation
2. Chronic irritation
3. Chemical imbalance
4. Stimulating antibodies
5. Viral infections

1. Acromegaly due to an increase in growth hormone and insulin growth factors-1
2. Endometrial gland hyperplasia due to hyperestrinism
-Increased risk for developing dysplasia
3. Bening prostatic hyperplasia due to an increase in dihydrotestosterone
4. Gynecomastia due to increased estrogen
5. Polycythemia due to an increase in erythropoietin

1. Thickened epidermis from constant scratching
2. Bronchial mucous gland hyperplasia in smokers and asthmatics
3. Cirrhosis of the liver due to alcohol excess

1. Hypocalcemia stimulates parathyroid gland hyperplasia
2. Iodine deficiency produced thyroid enlargement
-Combination of hypertrophy and hyperplasia

Examples: Graves' disease due to thyroid-stimulating antibodies (IgG) directed against thyroid stimulating hormone receptors

Examples: epidermal hyperplasia (wart) due to HPV

Dependent on the regenerative capacity of different types of cells

1. Divide continuously
2. Examples: stem cells in bone marrow, stem cells in the crypts of Lierberkuhn, and basal cells in the epidermis
3. May undergo hyperplasia as an adaptation to cell injury

1. Divide infrequently, because they are normally in the G0 resting phase
2. Must be stimulated (eg growth factors, hormones) to enter the cell cycle
3. Examples: hepatocytes, astrocytes, smooth muscle cells
4. May undergo hyperplasia or hypertrophy as an adaptation to cell injury

1. Highly specialized cells that cannot replicate
2. Examples: Neurons, skeletal, and cardiac muscle cells
3. Muscle cells undergo hypertrophy

Replacement of one fully differentiated cell type by another
-Substituted cells are less sensitive to a particular stress

1. Metaplasia from squamous to glandular epithelium
2. Metaplasia from glandular to other types of glandular epithelium
3. Metaplasia from glandular to squamous epithelium
4. Metaplasia from transitional to squamous epithelium

1. Example - distal esophagus epithelium shows an increase in goblet cells and mucus-secreting cells in response to acid reflux
2. This is called Barrett's esophagus
-Increased risk for developing dysplasia

1. Example - pylorus and antrum epithelium shows an increase in goblet cells and Paneth cells in response to H. pylori - induced chronic atrophic gastritis

2. This is called intestinal metaplasia
-Increased risk for developing dysplasia

1. Mainstem bronchus epithelium develops squamous metaplasia in response to irritants in cigarette smoke
2. Endocervical epithelium develops squamous metaplasia in response to the acid pH in the vagina
3. Both of the above alterations have an increased risk for developing dysplasia

1. Schistosoma hemtobium infection in the urinary bladder causes transitional epithelium to undergo squamous metaplasia
2. Increased risk for developing dysplasia

1. Stem cells have an array of progeny cells that have different patterns of gene expression
-Under normal physiologic conditions differentiation of these progeny cells is restricted
2. Metaplasia may result from reprogramming stem cells to utilize progeny cells with a different pattern of gene expression
3. Metaplasia is sometimes reversible if the irritant is removed

1. Hormones (eg estrogen)
2. Vitamins (eg retinoic acid)
3. Chemical irritants (eg cigarette smoke)

Disordered cell growth
-Precursor to cancer

1. Some types of hyperplasia
2. Some types of metaplasia
3. Infection
4. Chemicals
5. UV light
6. Chronic irritation of skin

1. Nuclear features
a. Increased mitotic activity, with normal mitotic spindles
b. Increased nuclear size and chromatin
2. Disorderly proliferation with loss of cell maturation as cells progress to surface

Sometimes the dysplasia reverses