what is the enlargement of cells due to an influx of water?
cell swelling
T/F: Cell swelling is not reversible.
False
Which cells are mostly commonly seen with cell swelling?
epithelial and endothelial cells
What is the general pathogenesis for cell swelling?
loss of homeostatic control for maintaining fluid and ion balance within the cell i.e. anoxic injury - decrease in ATP - decreased function of Na/K pump - increase of Na intracellularly - water follows Na gradient - cell swelling
If the entire organ is affected by cell swelling, what will it look like?
pale, swollen, increased in weight, cut surface will bulge
What is the term for the earliest visible change in a swollen cell, and what does it look like?
cloudy swelling; cytoplasm is swollen with a ground-glass appearance
What is the term for the advanced stage of cell swelling, and what does it look like?
hydropic degeneration; cytoplasm contains vacuoles, cytoplasm resembles spider web, non-staining spaces w/ill-defined borders
T/F: During cell swelling, free radical damage occurs in the mitochondria first and then the RER.
False, the RER is damaged before the mitochondria
What is fatty change or fatty lipidosis?
abnormal accumulation of lipids within cells
T/F: Fatty change is reversible.
True
T/F: Fatty change only occurs in organs that metabolize fat such as the liver, kidney, and heart.
False. Can occur in any organ
What are 6 ways of impaired metabolism that can cause hepatic fatty change?
1. Increased mobilization of fatty acids (pregnancy, not enough energy)
2. Decreased fatty acid oxidation (hypoxia)
3. Increased fatty acid synthesis (diabetes mellitus, need energy)
4. Decreased protein synthesis (free radical damage to RER)
5. Decreased
What is the gross appearance of hepatic lipidosis?
1. yellow (intensity varies with degree of change)
2. color change diffuse if entire organ affected and reticulated if lobule affected
3. swollen, heavy, greasy, friable
4. cut surface bulges
5. floats in water
What is the gross appearance of renal lipidosis?
1. diffuse pallor
2. pale streaking in cortex or medulla (common in old dogs)
What is the gross appearance of cardiac lipidosis?
pale streaks in myocardium
What are microscopic features of fatty change?
1. Cytoplasm has clear vacuoles (lipid removed during staining), can have one large or multiple small, with well well-defined borders
2. Lipid droplets stain red with Oil Red O stain and black with Sudan stains
What are three other lipid deposits?
1. Cholesterol
2. Exogenous lipids
3. Lipid storage diseases
What do cholesterol and cholesterol esters accumulations do to macrophages and smooth muscle cells?
fill them with small vacuoles with well-defined borders
What are 3 exogenous and endogenous lipid sources?
1. Mineral oil
2. oil vehicle for drugs
3. cellular lipids
What is glycogen accumulation?
excessive intracellular deposits of glycogen
T/F: Glycogen accumulation is common in the liver, kidney, heart, and skeletal muscle and is reversible.
True
What are the two categories of glycogen accumulation?
Physiologic and Pathologic
What are two examples of physiologic glycogen accumulation?
1. High storage in liver after meals
2. High abundance in liver is common in newborns
What are three examples of pathologic glycogen accumulation?
1. diabetes mellitus
2. steroid hepatopathy
3. glycogen storage diseases
How does diabetes mellitus cause glycogen accumulation?
deficiency of insulin causes a decrease in glucose uptake by cells which causes glycogen to accumulate in liver and kidney
How does steroid hepatopathy cause glycogen accumulation?
elevation in glucocorticoids causes an increase in gluconeogeneis and glyconeogenesis which causes glycogen accumulation in the liver
What are two kinds of glycogen storage diseases?
1. genetic enzyme deficiency: defective glycogen metabolism
2. lysosomal storage disease
What is the gross appearance of glycogen accumulation?
usually not visible grossly; liver may appear tan with severe involvement
What are microscopic features of glycogen accumulation?
1. Cytoplasm has clear vacuoles w/indistinct margins
2. cytoplasm has spider-web like appearance
3. Hard to tell b/n this and hydropic change
How can you tell the difference microscopically b/n hydropic change (cell swelling) and glycogen accumulation?
do a PAS stain
Cell swelling: Identify/name the lesion
Enlargement of cells due to influx of water
Cell Swelling: Causative agents
Cell injury due to hypoxia or free radicals
Viral infections
Cell Swelling: Pathogenesis
Loss of homeostatic control for maintenance of fluid and ion balance
Cell swelling: Histological appearance
Mild -> Cytoplasm uniformly swollen with cloudy appearance
Severe-> Cytoplasm is filled with vacuoles with ill-defined margins
Spider web cytoplasm from nuc to cell edges
Cell swelling: Gross appearance
Diffuse -> entire organ is pale, swollen and cut surfaces bulge
Focal-> small affected areas paler than rest of parenchyma
Cell Swelling: Sequelae
Cells may recover or get worse until irreversible
Swelling may interfere with vital functions
Cell Swelling: Clinical significance
May have leakage of cytoplasmic enzymes like ALT, can see that on chemistry, may indicate ischemic damage
Lipidosis: Identify/name the lesion
Unusual amount of lipid accumulation within cells
Lipidosis: Causative agents
Cell injury
Increased dietary consumption of lipids
Lipid storage diseases
Lipidosis: pathogenesis (6 of them)
Impaired fat metabolism:
Increased mobilization
Decreased FA oxidation
Increased FA synth
Decreased protein synth
Decreased phospholipid synth
Decreased lipoprotein secretion
Lipidosis: Histological appearance
Multiple sharply demarcated clear vacuoles in cytoplasm
Nucleus is displaced to periphery
Lipid verified in frozen section with Oil Red O OR Sudan stains
Lipidosis: organs most commonly affected
Liver
Kidney
Heart
Lipidosis: Gross appearance in liver
Yellow diffuse or centrolobular affected areas
Swollen, heavy, greasy, friable
Bulging edges
Floats in water
Lipidosis: gross appearance in kidney
Diffuse palor
Pale streaks (dog)
Intracellular lipid (cat)
Lipidosis: gross appearance in heart
Pale streaks in myocardium
Lipidosis: Sequelae
Cells may recover or get worse until irreversible
Fatty change my further impair cellular functions
Lipidosis: Clinical significance
may have leakage of intracellular enzymes, see evidence on chemistry
Glycogen accumulation: Identify/name the lesion
Excessive intracellular deposits of glycogen
Glycogen accumulation: Causative agents
Normal physiologic -> storage after meal; normal increase in neonates
Pathologic-> alterations in glucose metabolism (diabetes, Steroid hepatopathy, Glycogen storage disease)
Glycogen accumulation: Pathogenesis; Diabetes Mellitus
Decreased insulin
Decreased mobilization of glucose from tissue
Buildup of glycogen in liver and kidney
Glycogen accumulation: Pathogenesis: Steroid hepatopathy
Increased GCC stimulates increased glyconeogenesis
Glycogen accumulation: Pathogenesis Glycogen storage diseases
Genetic enzyme deficiency
Defective glycogen metabolism
Lysosomal storage disease
usually fatal
Glycogen accumulation: Histological appearance
Clear vacules with indistinct margins
Cytoplasmic strands
Swollen vacuolated neuc
Glycogen accumulation: what is it commonly mistaken for?
Hydropic change
Glycogen accumulation: how do you verify it?
PAS stain and distase
Glycogen accumulation: Gross appearance
Not usually visible grossly
- Liver may appear tan and pale when severe
Hard to differentiate from poor perfusion
Glycogen accumulation: Sequelae
Can return to normal if cause is reversible
Secondary injury and cell death (espec in storage diseases)
Glycogen accumulation: Clinical significance
?? Cell death, liver death = body death?
Hyaline Droplets: Identify/name the lesion
Presence of intracellular hyaline material
Small eosinophilic bodies within cytoplasm
Usually proteinaceous
Hyaline Droplets: Causative agents
Increased uptake of material by endocytosis
Build-up of secretory material
Degenerative change (large secondary lysosomes; Myelin bodies)
Hyaline Droplets: Pathogenesis
Can be normal Or pathogenic
Hyaline Droplets: Normal causes of it
Renal tubule uptake from urine filtrate (usually small amts)
Colostrum in enterocytes of neonates
Hyaline Droplets: abnormal causes of it
Endotoxemia (Lysosomes in cells engulf broken down organelles)
Glomerular injury (Loss of protein in urine causes increased uptake by renal tubular epithelium)
Hyaline Droplets: Histological appearance
Round or oval bodies with well defined borders in cytoplasm
Eosinophillic
Amorphus
Homogeneous
Variable sizes
Hyaline Droplets: gross appearance
Not visible
Hyaline Droplets: Sequaleae
If degenerative change, cell injury will progress
Hyaline Droplets: Clinical significance
Normal
Indicative of cell injruy (espec in kidney or liver)
Amyloidosis: Identify/explain the lesion
Pathologic proteinaceous material deposited EXTRAcellularly in beta-sheet arrangements
Contains glycoprotein
Occurs in humans and animals
Amyloidosis: T/F the nature of the amyloid material can vary greatly
True
Amyloidosis: Causative agents
Soluble protein made insoluble due to beta-sheet arrangement
Insoluble protein builds up extracellularly
Amyloidosis: Pathogenesis
Inflammation-> IL 1, 6 by macs
SAA (serum amyloid associated) protein in hepatocytes
Distributed systemically by albumin
Proteolysis, macrophage action causes alteration of basement membrane proteins
Form beta-sheet which accumulate
Amyloidosis: Histological appearance
Amorphous
Eosinophilic
Orange with green birefringence
Amyloidosis: What are the 3 major organs this occurs in, and where do you see it in each organ
Liver-> sinusoids
Kidney-> glomeruli
Spleen-> follicles and sinuses
Pancreas -> sinusoids in pancreatic islets
Amyloidosis: Gross appearance
+/- lesions
Enlarged
Firm
Pale tan to gray, spleen is pale
Mulitple foci
Stains blue/black with Lugol's iodine and H2SO4
Amyloidosis: Sequela
pressure atrophy of cells
Interference with organ function
Can cause fibrillogenesis
Amyloidosis: Clinical significance
Organ dysfunction
Kidney-> proteinuria, renal failure
Pancreas-> diabetes mellatus
Liver-> hepatic failure, hemorrhage
Spleen-> hemorrhage
Hyaline casts: identify/explain the lesion
Hyaline material in renal tubular lumins
Hyaline casts: causative agents
renal disease
Hyaline casts: Pathogenesis
protein leakage through glomeruli
Often Tamm-Horsfall protein
Hyaline casts: Histological appearance
Tubules distended with eosinophilic homogenous material
+/- hyaline droplets in epithelium
Hyaline casts: Gross appearance
Severe distended tubules seen as cysts
Hyaline casts: sequelae
Death due to underlying renal disease
Hyaline casts: Clinical significance
Can be identified by urinalysis in cats
Fibrinoid Change (necrosis): Identify/explain lesion
Hyaline material (+/- fibrin) within blood vessels
Fibrinoid Change (necrosis): Causative agents
Viruses
Bacteria
Idiopathic
Mact cells/eosinophils (hypersensitivity)
Fibrinoid Change (necrosis): Pathogenesis
Ab-Ag complexes deposited in vessel walls form activated complement and necrosis
Direct damage to vessel wall collagen
Fibrinoid Change (necrosis): Histological appearance
Eosinophilic homogenous deposits
Loss of cell borders and nuclei of smooth myocytes in tunica muscularis
+/- thickening of vessel wall
+/- inflammatory cells
Can be circumferential or focal
Fibrinoid Change (necrosis): Gross appearance
May not see grossly
Tortuous thickening of blood vessels
Evidence of vessel damage (edema, hamorrhage)
Fibrinoid Change (necrosis): clinical significance/sequela
Edema
Hemorrhage
Necrosis
Connective Tissue hyaline: Identify/explain the lesion
Deposition of dense fibrous CT
Hyalinized fibrous CT
Connective Tissue hyaline: Causative agents
Ischemia
Decreased nutrients
Chronic injury
Aging change
Connective Tissue hyaline: Histological appearance
Eosinophilic
Homogeneous
Connective Tissue hyaline: Gross appearance
May be visible grossly
Smooth
White
Glossy
Firm
(scar tissue)
Connective Tissue hyaline: sequalae
No effects
Change in elacticity may interfere with organ function
Fatty infiltration: Identify/explain lesion
Accumulation of fat EXTRACELLULARLY in stromal tissue
Adipocytes where they shouldn't be found
Fatty infiltration: 5 causative agents
Atrophy
Necrosis
Obesity
Idiopathic
Aging
Fatty infiltration: Histological appearence
Excessive, normal appearing adipocytes in interstitium
+/- necrosis, atrophy, inflammation, scarring
Fatty infiltration: Gross appearance
Pale white or yellow areas of tissue
Fatty infiltration: Sequala/clinical relavance
Obesity
5 types of amyloidosis
Immunocyte derived
Reactive systemic
Endocrine
Senile
CNS
Immunocyte derived classification
Humans only
Systemic
Primary
Chemical nature of immunocyte derived amyloidosis
AL protein (amyloid light chain)
Derived from light chains secreted by plasma cells
Pathogenesis of immunocyte derived amyloidosis
Neoplasm or blood cell dyscrasia
Increase secretion of light chains of Ig (aka Bence-Jones protein)
Proteolysis occurs
Amyloid formation occurs
Reactive Systemic amyloid in human classification
Systemic
Secondary to inflammatory or chronic disease
Chemical nature of Reactive Systemic Amyloid
AA (amyloid associated) protein
Derived from SAA produced in liver and follows SAA pathogenesis
Systemic amyloidosis in animals
Reactive systemic (most common)
Familial amyloidosis (Sharpeis and abyssinians)
Reactive systemic amyloidosis in animals is expressed in what organs
Renal
Hepatic
Familial amyloidosis
Renal mainly
But can see in other tissues
Endocrine Amyloidosis classification
Localized
Endocrine amyloidosis chemical nature
Polypeptide hormones or prohormones
Amylin (islet amyloid pancreatic polypeptide, procalcitonin)
Endocrine amyloidosis pathogenesis
+/- neoplastic process
proteolysis of protein hormone to form amyloid
What are 3 types of localized amyloidosis in animals?
Endocrine amyloid (cats)
Neoplasm
Nasal amyloidosis (horses)
Endocrine amyloid in cats
Pancreatic islets affected
Older cats with or without diabetes
Lesions more severe in diabetics
May be casual relationship
neoplasms causing amyloidosis in animals
C-cell tumors in bulls
Cutaneous plasma cell tumors (AL proteins)
Odontogenic neoplams
Senile amyloid classification
Localized
Chemical nature of senile amyloid
Transthyretin (serum protein that binds and transports thyroxine and retinol)
Alpha atrial natriuretic peptide (ANP)
pathogenesis of senile amyloid
Defective protein or proteolysis forming amyloid
Senile amyloidosis in animals
Apolipoprotien AI in lungs of old dogs
CNS amyloid classification
Localized
Chemical nature of CNS amyloid
B-2 protein (A4) may be derived from transmembrane protein
Conditions in humans caused by CNS amyloid
Alzheimer's
Down's syndrome
hereditary
Pathogenesis of CNS amyloidosis
Defective protein or proteolysis resulting in amyloid formation
CNS amyloidosis in animals
Old dogs
Non-human primates
Scrapie in sheep
6 Factors contributing to fibrillogenesis in amyloidosis include
Primary protein structure
Increase in and proteolytic cleavage of precursor proteins
Post-translational modifications of proteins
Tissue specific factors
Abnormal protein structure due to mutations
Role for chaperone proteins (heat shock) that inhibit or
Cloudy change characteristics
Earliest visible change due to cell swelling
Old term
Cytoplasm is uniformly swollen and has a cloudy or "ground-glass" appearance
Hydropic change charactertistics
Hydropic degeneration
Advanced stage of cell swelling
You see vacuoles not well defined
May see strands of cytoplasm in spider-web fashion
Vacuolar change
Microscopic features of cell swelling and glycogen accumulation since these two changes are difficult to differentiate
Fatty change may sometimes be included, but only if you are a bad pathologist (according to Dr. K)