Reversible Cell Injury + Accumulations Flashcards
Reversible Injury
injured cell can regain homeostasis + return to a morphologically + functionally normal state
no reliable way to tell when an reversible injury becomes irreversible
one consistent feature = cell swelling
Reversible Injury Gross + Histopathology Appearance
one consistent feature = cell swelling
Grossly (if many cells affected)
- palor
- organomegaly
- decreased specific gravity (increased water)
Histopathology:
- increased cell size with rounding
- pale, finely vacuolated to granular appearance (cloudy swelling)
- nuclei not displaced + may be swollen
Nomenclature varies depending on cell type:
- vacuolar degeneration - always works
- hydropic degeneration - used in most tissues
- ballooning degeneration - specific to keratocytes
- cytotoxic edema - specific to CNS cells
Hypertrophy v Acute Degeneration
Normal Cell Volume
water moves passively across CM in response to osmotic pressure gradient generated by Na + proteins
major controller of cell volume = Na/K ATPase pump
- fueled by ATP
- drives Na out of cell in exchange for K
susceptible players in this scenario:
- physical barrier funtion of membranes
- pump requires energy which requires oxgen
- membrane proteins/enzymes maintaining ion conc. + membrane function
Mechanisms + Causes for Cell Swelling
Mechanisms responsible for acute swelling:
- damage to cellular membranes
- injury to enzymes regulating ion channels on membranes
- failure of energy (ATP) production
Some potential causes for cell swelling:
- mechanical injury (trauma)
- hypoxia
- toxicity
- free radicals
- infectious (viral + bacterial)
- immune-mediated
Hypoxia + Cell Swelling
Hypoxic Liver Injury
causes contributing to hypoxia + centrilobar hepatocellular degeneration + necrosis:
- anemia
- decreased O2 carrying capacity of RBCs
- respiratory compromise
- heart failure
Why centrilobar hepatocytes?
- are at the very end of the road for oxygenated blood
- also have a lot of enzymatic activities requiring O2 + energy
- while hypoxia is common cause, hepatic toxins should also be considered
Significance + Fate of Cell Swelling
injured cells no longer able to control water + electrolytes are no better to maintain other cell functions as well:
- skin = decreased barrier function
- liver = decreased hepatic function
- nervous system = decreased nerve impulse condition
important to consider extent/amount of damage
- only a few cells affected = no signs/subclinical
- most cells affected = clinical signs
this change is REVERSIBLE
however if injury is severe or not removed promptly = CELL DEATH
Intracellular Accumulations
a manifestation of metabolic derangements in cell -> accumulation of abnormal amounts of substances
2 categories of substances that accumulate:
1) normal cellular constituents
- water, lipids, proteins,carbs
2) abnormal substances
- exegenous or endogenous
may accumulate in cytoplasm (typically) or nucleus
may accumulate transiently or permanently
possible consequences:
- harmless (incidental)
- varying degrees of injury (toxic)
if overload can be controlled/stopped -> reversible
4 types:
1) abnormal metabolism
2) defect in protein folding, transport
3) lack of enzyme
4) ingestion of indigestible materials
Abnormal Metabolism
normal endogenous substance produced at normal/increased rate BUT rate of metabolism is inadequate to remove it -> accumulation
ex:
- hepatic lipidosis
- renal tubular proteinosis
- steroid hepatopathy
Defect in protein folding + transport
an abnormal endogenous substance
- usually from genetic defect
abnormaity -> improper folding, transport + degradation -> accumulation
examples:
- mutated alpha1-antitrypsin in liver
- degenerative CNS diseases
Lack of an Enzyme
a normal endogenous substance accumulates bc of defects in enzyme required to metabolize substance
- defects typically inherited
substance will generally accumulates in lysosomes
ex) lysosomal storage diseases
Indigestion of indigestible materials
an abnormal endogenous substance is deposited + accumulates bc:
- cell doesn’t have enzymatic machinery to break it down NOR ability to transport to another site
ex) pneumonoconiosis
Lipidosis/Steatosis/Fatty Change
accumulation of TGs + other lipid metabolites (fats + cholesterols) within parenchymal cells
most commonly seen in liver -> main organ involved in lipid metabolism
- may be seen in other organs as well typically as a result of altered liver function
Hepatic Lipidosis
Grossly:
- slightly swollen w/ rounded edges
- diffusely pale + yellow-tinged
- may feel greasy + friable
- may float in formalin
Histo:
- hepatocytes enlarged/distended by 1-few clear punctuate cytoplasmic vacuoles -> extend depends on severity
- large vacuoles may displace nucleus + make cell look like an adipocyte
underlying pathogenesis centers on biochemical pathways of FFA formation + metabolism in liver
FFAs derived from TGs provide large component of basal energy needs. FFAs obtained from:
- diet, chylomicrons in blood, adipocytes in fat stores
5 mechanisms that may contribute to hepatic lipidosis:
1) excessive FFAs delivered by gut or adipose tissue
2) decreased oxidation or use of FAs d/t mitochondrial injury/hypoxia
3) impaired synthesis of apoprotein (toxins)
4) impaired combo of TGs + proteins to form lipoproteins
5) impaired release of lipoproteins from hepatocytes
Hepatic Lipidosis in vet med
most commonly arises from conditions that cause increased mobilization of body fat stores -> increased demands over short periods of time
- late pregnancy in ruminants
- early lactation in dairy cows (ketosis/milk fever)
- anorexia in toy-breed puppies
- anorexia in obese cats
- DM
Fatty Change v Fatty Infiltration
Fatty change = lipidosis often related to altered lipid metabolism
- fatty vacuolation WITHIN cell cytoplasm
Fatty Infiltration = infiltration of mature adipocytes into non-adipose tissues -> NORMAL lipid metabolism
- normal level of mature adipocytes present for storage
- in some instances of tissue atrophy, cells lost may be replaced by adipocytes
Atherosclerosis
vascular disease of major important in humans (not really in vet med)
- experimental dz in pig, rabbit + chicken
- natural dz can be seen in birds, aged pigs, dogs w/ hypothyroidism + DM
accumulation of cholesterol + chol. esters in cytoplasm of smooth muscle cells + macrophages in arterial walls -> luminal thinning
- Gross = vessels thicked, tortuous, firm, yellow-white + may be gritty (mineralized)
- Histo = foamy appearance on histo + cholesterol clefts
Renal Tubular Proteinosis
function of glomerulus = filter bad stuff out, keep good stuff in
- what little proteins that get through are reabsorbed by prox. renal tubules
damage to glomerulus -> increased protein entering prox. tubules -> increased protein reabsorption in tubular epithelial cells -> cytoplasmic protein accumulation
Histo = hyaline droplets within epithelial cell cytoplasm
- reversible change -> protein absorbed by vesicles that fuse with lysosomes + then degraded
indicates elevated protein being lost by glomerulus
Mott Cells + Russell Bodies
accumulation of protein within cytoplasm of plasma cells
plasma cells responsible for generating + secreting antibody
- accumulation of antibody within cell -> bright pink, glassy globules within cytoplasm
- globules = russell bodies
- described as manifestation of cellular indigestion of ER (constipated)
seen in some chronic inflammatory diseases like:
- plasma cell stomatitis in cats
- plasma cell pododermatitis in cats
- IBD
Glucocorticoid Hepatopathy
excess amounts of glucocorticoids + steroid hormones -> increased glycogen prod. + storage in liver
- endogenous elevations = hyperadrenoocorticism
- exogenous = typically iatrogenic
Gross:
- enlarged, pale liver that may be mottled
- NOT friable or grease like HL
Histo:
- markedly enlarged hepatocytes by clear space in cytoplasm -> more feathery + indistinctive vacuoles
- typically no displacement of nucleus
Hepatic Lipid v Glycogen Accumulation
Lipid
- abnormal lipid metabolism
- clear punctuate vacuoles
- possible displaced nucleus
- stains = Oil Red O +, PAS -
Glycogen
- abnormal glucose + glycogen metabolism
- small, fuzzy to foamy vacuoles
- no displaced nuclei
- stains = Oil Red O - , PAS +
Lysosomal Storage Diseases
group of disorders characterized by accumulation of material within lysosomes
- absence of specific enzymes required for breakdown of material
most are genetic/inherited
- some can be induced by toxins
while all cell types vulnerable -> long-lived post-mitotic cells tend to be most affected (neurons + mm)
clinically -> young animal with progressive NM impairement
Histo:
- cells distended by accumulated material in cytoplasm
- some characterizd by accumulation of macrophages engulfing material
- may see other signs of disease = inflammation, degeneration, atrophy, loss of cells, etc.
Alpha-mannosidosis in cats
defiency of alpha-mannosidase -> blocks catabolism of mannose/N-acetylglucosamine oligossacharides
accumulation of material within lysosomes of neurons + other cells -> neurologic dz
Globoid Cell Leukodystrophy
deficiency in galactocerebrosidase -> material accumulation in oligodendrocytes, schwann cells + macrophages
- destruction of myelin-producing cells + myelin that’s produced wrong
- macrophages (Gitter cells) come in to clean up mess but also accumulate material
Rhomboid Crystalline Protein Inclusions
non-infectious inclusion
AKA crystalloids or brick inclusions
incidental finding
- found in nuclei of normal hepatocytes + renal tubular epithelial cells
- mostly found in old dogs
large, eosinophilic, rhomboidal
- can be so large they distore nucleus or cell
Lead inclusion bodies
if timed correctly, you may see these in renal tubular epithelial cells in cases of lead toxicity/poisoning
hard to see on H+E staining
- smudgy, pale, amphophilic irregular
best highlighted by acid-fast staining
- bright red intranuclear staining
inclusion represents lead + protein
Viral Inclusion Bodies
some viruses will produce IC inclusions
- may be in nucleus, cytoplasm or both
- typically represents accumulation of viral proteins, virions or viral particles that may be mixed with other proteins
presence/absence often depends on where in timeline of infection you are:
- more often seen in early infxn
- disappear as infected cells lysed + cleared
in general (ALWAYS EXCEPTION)
- DNA viruses -> intranuclear inclusions
- RNA viruses -> intracytoplasmic inclusions
