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VM 605 General Pathology > Reversible Cell Injury & Cellular Accumulations > Flashcards

Reversible Cell Injury & Cellular Accumulations Flashcards

1
Q

What is reversible cell injury?

A

Injured cell can regain homeostasis & return to a morphologically & functionally normal state

Cellular swelling is the SINGLE FEATURE that can be recognized under a light microscope

Swollen cells have a paler cytoplasm

Fatty change (lipid accumulation) & glycogen accumulation are also considered to be reversible hepatocyte injuries

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2
Q

What is the mechanism for cell swelling (reversible cell injury)?

A

Hypoxic Injury/ Mitochondrial Damage

Depletion of cellular O2 → decreased oxidative phosphorylation → less ATP produced → failure of ATP dependent Na+/K+ ATPase pumps → influx of Na+/Ca2+/ H2O into cell → Cell loses K+ & Mg2+

Influx of H2O causes cell swelling

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3
Q

Direct Membrane Injury that results in Cell Swelling

A

Free radical damage (lipid peroxidation)

Covalent binding by toxins

Interference with ion channels (ionophore toxicity)

Insertion of transmembrane complexes

Bacterial cytotoxins

MAC complex from complement system - Immune Molecules

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4
Q

Gross Appearance of Reversible Cell Injury

A

Increased pallor (paler color)

Increased weight

Left is abnormal

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5
Q

Cellular Swelling under Light Microscopy

A

Paler looking

Cells are enlarged w/ many small, colorless vacuoles (pinched off segments of ER, Golgi & swollen mitochondria

Paler cytoplasm

More cytoplasm present

Some cells might have increased eosinophilia of the cytoplasm

As cell swelling progresses to irreversible cell injury, specifically necrosis, eosinophilia becomes more apparent

Darker pink, glassy appearance of cytoplasm

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6
Q

Balooning Degenration in the Oral Mucosal Epithelium

A

Reversible cell injury

Progression to colorless cytoplasm:

Pale pink → Clear

Arrows point to viral inclusions (pink)

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7
Q

Progression from

Reversible Cell Injury to Irreversible Cell Injury

A

Progression to irreversible cell injury when reversible is no longer reversible

Irreversible cell injury leads to cell death via:

Apoptosis

“Programmed cell death”

Not usually associated with membrane rupture that occurs with oncosis

Necrosis

Death by swelling and subsequent cell membrane rupture

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8
Q

Intracellular Accumulations

(What are they?)

A

Injured cells can accumulate endogenous by-products or exogenous substances b/c of:

  • Metabolic abnormalities
  • Genetic mutations
  • Lacking enzyme
  • Defect in protein folding
  • Exposure to indigestible exogenous substances

Substances can accumulate:

  • Cytoplasm
  • Within organelles
  • In the nucleus
  • May be produced within the cell or elsewhere
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9
Q

4 Pathways to Abnormal Intracellular Accumulations

A

Inadequate removal of a normal substance

  • Defect in packaging & transport mechanisms

Genetic or acquired defects that result in an accumulation of an abnormal endogenous substance

  • Folding, packaging, transport, secretion defects

Failure to degrade metabolites due to inherited enzyme deficiency

  • Storage diseases

Accumulation of an abnormal exogenous substance

  • Cell doesn’t have the ability to degrade, transport or remove substance
  • Ex. Carbon or silica particles
    • Lungs affected (pulmonary macrophages)
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10
Q

Types of Intracellular Accumulations

A

Lipids

Lipidosis- Steatosis- Fatty change (synonomous)

Glycogen

Proteins

Autophagic Vacuoles

Crystalline Protein Inclusions

Viral Inclusions

Lead

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11
Q

Lipid Intracellular Accumulations

A

Accumulation of lipids within parenchymal cells (functional tissue of an organ)

  • Most common in liver
    • Liver is main organ in lipid metabolism
    • Kidney is 2nd most common

All classes of lipids can accumulate:

  • Triglycerides
  • Cholesterol/cholesterol ethers
  • Phospholipids
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12
Q

Causes of Intracellular Lipid Accumulations (3)

A

Increased mobilization of free fatty acids

  • Metabolic machinery can’t keep up

Abnormal metabolism in the liver

  • Ex. Hepatic toxicosis

Impaired release of lipoproteins

  • Ex. Cat with a genetic lipoprotein lipase deficiency
  • Ex. hepatic lipidosis in toy breed puppies
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13
Q

Fatty Liver, Hepatic Lipidosis

Gross Appearance

A

Steatosis

Uniform pale yellow-tan color

Liver is enlarged, with rounded edges

  • Normal margins of a liver lobe should come to a point

Liver bulges on incision

May feel greasy

May float in formalin

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14
Q

Fatty Liver, Hepatic Lipidosis

(Lipid Intracellular Accumulations)

Light Microscopy

A

Severely affected liver

All hepatocytes contain unstained, sharply defined cytoplasmic lipid vacuoles

Nucleus is displaced to the periphery of the cell

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15
Q

Intracellular Lipid Accumulations

Cholesterol and Cholesterol Esters

(Atherosclerosis)

A

Atherosclerosis

  • Accumulation of cholesterol esters w/in SM of arterial vessel and w/in macrophages
  • Filled with lipid vacuoles containing cholesterol & cholesterol esters
  • Cells have a foamy appearance
  • Only significant in pigs, chickens and rabbits
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16
Q

Intracellular Lipid Accumulations

Cholesterol & Cholesterol Esters

Xanthomas

A

Xanthomas

  • Accumulation of cholesterol-laden macrophages in tissues (mainly skin)
  • Arise from metabolism disorders
    • Hyperlipidemia in cats
    • Diabetes mellitus
      • high blood glucose levels & glucose spills into urine
    • High fat diets
17
Q

Intracellular Glycogen Accumulations

A

Stored mainly in hepatocytes & muscle during homeostasis

Stores can be depleted with starvation (anorexia)

Glycogen accumulation occurs in:

  • Metabolic abnormalities of skeletal muscle
  • Glycogen storage diseases (glycogenesis)
  • In the liver
18
Q

Intracellular Glycogen Accumulations in the Liver

A

Glucocorticoid (Steroid) Hepatopathy - chronic excess of corticosteroids (endogenous or exogenous)

  • Hyperadrenocorticism (Cushing’s)
    • Functional pituitary or adrenal tumors
  • Excess exogenous corticosteroids (iatrogenic)
    • Prolonged or high-dose corticosteroid accumulation

Image: Glucocorticoid-induced Hepatopathy, Liver, Dog

  • Extensive accumulation of glycogen in hepatocytes
  • Results in a enlarged, pale-brown to beige liver
  • Arrows point to swollen hepatocytes with huge amounts of cytoplasmic vacuolation from glycogen accumulation
19
Q

Lipid Vacuoles vs. Glycogen Vacuoles

(Intracellular Accumulations in the Liver

A

Lipid Vacuoles:

  • More discrete
  • Round
  • Displace nucleus of hepatocyte

Glycogen Vacuoles:

  • Blend better with cytoplasmic constituents
  • Lacey and eosinophilic
  • Irregular shape
  • No displacement of nucleus

Both found in the liver

20
Q

If you put a section of fatty liver in formalin…

A

It will float

21
Q

Intracellular Protein Accumulations

as

Reabsorption Droplets in Proximal Renal Tubules

A

Reabsorption droplets in proximal renal tubules

  • Seen in renal disease where there is protein loss in the urine
    • Protein-losing nephropathy (low protein in blood & high in urine)

Disease that affect glomerular filtration →

  • More protein leaking into renal tubules →
    • heavy reabsorption of proteins by proximal tubular epithelial cells →
      • protein droplet accumulation in cells (they can only absorb so much)
22
Q

Intracellular Protein Accumulations

Mott Cells & Russell Bodies

A

Proteins that accumulate may be normally produced by the cell but are present in excessive amounts

  • Ex. Plasma cell producing too much immunoglobulin
    • “Mott Cell”
  • Accumulation of excessive immunoglobulin expands ER and produces large, homogenous eosinophilic inclusions = Russell bodies
    • Russell bodies = ER swollen with protein bodies
23
Q

Intracellular Accumulations - Autophagic Vacuoles

A

Autophagy

  • Process where cell eats its own contents
  • Survival mechanism during periods of nutrient deprivation

Involved in many physiologic and pathologic processes

  • H&E appear as small, clear, & colorless vacuoles in the sarcoplasm of myofibrils
    • Look like holes in skeletal muscle
24
Q

Intracellular Accumulations

Crystalline Protein Inclusions

A

Rhomboid crystalline protein inclusions

  • Aka crystalloids
  • Common in hepatocytes & tubular epithelial cells of older dogs
  • Marker of cell aging
  • Appear as rectangular, pink, intranuclear inclusions
25
Q

Intracellular Accumulations

Viral Inclusions

A

Presence of viral inclusions depends on chronicity of disease

Expect to see inflammation & remodeling

  • Early in disease = inclusions usually present
  • If animal survives, more chronic or reparative lesions are seen, then inclusions probably wont be there
  • Viral inclusions can be intranuclear, intracytoplasmic or both
    • Generally, DNA viruses have intranuclear inclusions
    • RNA viruses have intracytoplasmic
      • Exceptions: Pox virus, Canine Distemper (heat-shock protein)
26
Q

Intracellular Accumulations

Viral Inclusions

Canine herpesvirus & Herpesviral nephritis

A

Canine herpesvirus:

  • Intranuclear red inclusions
  • Chromatin from nucleus is marginated (pushed out)

Herpesviral nephritis:

  • Turkey egg kidney
  • Splotchy
  • Red foci correlate to areas of necrosis
27
Q

Intracellular Accumulations

Viral Inclusions

Canine parvovirus & Canine parvovirus enteritis

A

Canine parvovirus:

  • Pink, intranuclear inclusions

Canine parvovirus enteritis

  • Necrotizing enteritis (dead mucosa)
28
Q

Intracellular Accumulations

Viral Inclusions

Canine Adenovirus & Adenoviral Hepatitis

A

Canine adenovirus

  • Pink, intranuclear inclusions
  • Larger inclusions than canine herpes virus

Adenoviral hepatitis

29
Q

Intracellular Accumulations

Viral Inclusions

Canine Distemper Virus

A

Canine Distemper Virus (CDV)

  • Pink intranuclear & intracytoplasmic inclusions

Bronchointerstitial pneumonia

  • Lung was never deflated
  • Something preventing exhalation
30
Q

Intracellular Accumulations

Viral Inclusions

Rabies Virus in a Cow

A

Rabies virus in a cow

  • Negri bodies
    • Red to brown intracytoplasmic inclusions
31
Q

Intracellular Accumulations

Lead

A

Lead Poisoning

  • Can produce intranuclear inclusions in renal tubular epithelial cells
  • Mixture of lead + protein
  • Acid-fast positive inclusions (red)

VM 605 General Pathology (3 decks)

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