Foundations (VMED 5275): Cell Degeneration, Necrosis, Injury, and Death

the cell functions due to

genetic programs of metabolism

differentiation

specialization

constraints of neighboring cells

availability of metabolic substrates

cellular adaptations

severe physiologic stresses and pathologic stimuli, causing physiologic and morphologic changes

cellular adaptation will cause

new but altered steady states

preserve viability of the cell

modulate fxn.responding to stimuli

cellular injury results when

the limits of adaptive response to a stimulus are exceeded or if a cell is exposed to an injurious agent or stress

cell injury is reversible to a certain point

true

if stimulus persists or is severe enough

cell reaches point of no return, irreversible cell injury and cell death

standard cells organelles

synthesis of lipids, proteins, CHOs

energy production

transport of ions and other molecules

cells respond to homeostatic changes

adaptation

examples of cellular adaptations

increasing muscle mass

increasing p450 fxn. in oxidation expression in hepatocytes

cells respond by increasing/decreasing content of organelles

atrophy

reduction in mass of tissue or organ

hypertrophy

increase in the size of cells, resulting in enlargement organs

hyperplasia

increased number of cells in an organ or tissue

metaplasia

transformation or replacement of one adult cells type with another

cell swelling

acute change in reversible cell injury

cell enlargement

seen in chronic sublethal injury

signal of hypertrophy

increased proteins content of cells

increased organelle number

myofibrils

MITOCHONDRIA

endoplasmic reticulum

hypertrophy may not be always advantageous to the animal

true

list 4 changes as cellular adaptations

atrophy

hypertrophy

metaplasia

hyperplasia

increase in size of cells

hypertrophy

cell injury

loss of the ability to maintain the normal or adapted homeostatic state

unable to balance/regulate internal environment

extent of injury varies

severity of stimulus

type of cell involved

matabolic state a time of injury

cell degeneration

reversible cell injury\ can be unclear to differentiate between adaptation

histologic slides may not be able to

determine if a cell is getting worse or better

may not be able to determine if the injury would have been reversible or not

morphologic chnages lag behind functional changes

true

hallmarks of cells degeneration (cellular accumulations)

cell swelling

fatty change

glycogen accumulation

lipofuscin and ceroid = oxidized product form membrane to lipids=yellow to brown

hyaline changes = dense, homogenous, glossy, translucent many causes protein leakage

amyloid

mucinous changes = gelatinous, semisolid, slimy, clear, stringy

calcification

gout

cholesterol crystals

inclusions

reduction in the mass of a tissue or organ, loss of cells, reduction in size of cells

atrophy

disuse atrophy

decrease workload

dystrophic atrophy

decreased nutrition

endocrine/hormonal atrophy

loss of hormonal stimulation

anemic atrophy

decreased blood

neural atrophy

loss of innervation

pressure atrophy

tissue compression

physiological atrophy

senile atrophy

cellular atrophy occurs when

reversible damage occurs

reduced functional capacity

continue to control internal environment and produce sufficient energy for metabolic stsate

adrenal glands - addisonian crisis can occur when

sudden withdrawal of corticosteroids

prolonged cellular atrophy may lead to

death of some cells

loss of muscle cells

hypertrophy

increase in organ cell size

increases organ size without cellular proliferation

hyperplasia

increase in number of cells in an organ

in the heart, hypertrophy does not change underlying problem such as valvular stenosis

true

heart hypertrophy can cause

decreased ejection volume and may eventually end up in organ failure

cellular hyperplasia

increase in number of the principal cells of a tissue or organs

cellular hyperplasia can only occur in a cell population that is capable of mitosis

true

epithelial cells, hepatocytes is an example of cells where hyperplasia can occur

true

striated muscle and nervous system tissues have negligible capacity to proliferate and in general do not undergo hyperplasia

true

Hyperplasia differs from neoplastic cellular proliferation in that it generally subsides if the stimulus is removed

true

metaplasia

one differentiated cell type (epithelial or mesenchymal) is replaced by another cell type

suqamous metaplasia is a reparative response to

chronic inflammation (mastitis)

hormonal imbalance

vitamin A deficiency

trauma

amyloid

complex protein that accumulates within cells, complex homogeneous pink material

calcification

abnormal accumulation of calcium salts in soft tissue

gout

in bird and reptiles assoc. with renal disease due to low excretion of urates

cholesterol crystals

areas of previous hemorrhage or inflammation

inclusions

viral diseases

intranuclear/intracytoplasmic

early, almost universal sign of injury

cell swelling

will often look cloudy and pale

hydrophobic degeneration

cell swelling results from

loss of control of ions/water with net uptake of watewr

loss of energy control/production

not incompatible with life of the cell depending on severity and is often mild and rapidly reversible

also occurs in lethal injury

Fatty change

accumulation of neutral fats in a cell, specialized in cells that metabolize lipids(hepatocyte,myocardial cells)

pathogenesis of fatty change

overload = diabetes/ anorexia

injury to cells = toxins/anoxia

deficiencies = methionine/choline

lipidosis = normal in milk diet/fatty meals

hepatic lipidosis

increased mobilization of body fat stores

glycogen accumulation is due to

severe prolonged hyperglycemia

presence of high levels of glucocorticoids

lysosomal storage disease

pathogenesis for glycogen accumulation

prolonged, severe hyperglicemia = diabetes

increased corticosteroids

cushing’s syndrome = adrenal glands

iatrogenic

enzyme diseases

lipofuscin is a pignment that accumulates in

long lived postmitotic cells = neurons/cardiac myocytes

hyaline cartilage

intracellular or extracellular proteinaceous substances that take up eosin dye homogeneously

examples of hyaline changes

protein casts in renal tubules

plasma in blood vessel walls

thickened basement membranes

acute respiratory distress syndrome

fibrin thrombi

amyloidosis

protein misfolding disorders

you’ll see pale, waxy and translucent

gross appearance of lipidosis

yellow, priable, greasy organ

congo red stain highlights

amyloid deposition due to misfolding proteins

primary amyloidosis

the primary site affected by the deposition

secondary/systemic amyloidosis/serum amyloid AA

produced mainly by hepatocytes cleaved into fragments deposited as amyloid fibrils in kidneys, liver, spleen

due to chronic inflammation

dyscracias or neoplastic proliferations of plasma cells (B cells) produce

immunoglobulin light chains derived from plasma cells AL amyloid

some localized forms in nose of horses

calcification

abnormal deposition of calcium salts

dystrophic calcification

in areas of necrosis

calcification of skin = calcinosis circumscripta calcinosis cutis

vitamin E or selenium deficiency : my

metastatic calcification

HYPERCALCEMIA

chronic kidney disease

renal failure

toxicosis with vit.D

increased secretion of PTH

resorption of bone tissue

in calcification, renal failure will cause calcium deposition in

lungs, pleura and endocardium

calcinosis circumscripta

calcium deposition usually at bony prominences (dermis or subcutis)

calcinosis cutis

seen mainl

gout has not been reported in

domestic mammals

gout pathogenesis

kidney failure

disturbance of purine meatbolism

high protein diets

2 forms of gout

visceral (common) and articular (rare)

cholesterol crystals

in areas of previous hemorrhage, necrosis or inflammation, chronic process

viral inclusion bodies

certain viral diseases

intranuclear or cytoplasmic or both

intranuclear viral inclusion

DNA viruses

herpesvirus

adenovirus

parvovirus

intracytoplasmic inclusions

RNA viruses

rabies

canine distemper

irreversible cell injury

transition between living and dead cell

morphologic hallmarks of irreversible cell injury

severe mitochondrial swelling

large flocculent densities in mitochondrial matrix

increased loss of proteins, enzymes, co-enzymes

greatly increased membrane permeability

causes of cell damage

hipoxia

ischemia

hipoxia

decrease in oxygen to affectes tissues

ischemia

loss of blood flow to affected tissues

causes for hypoxia

decreased blood oxygen : pulmonary / non-pulmonary

decreased blood flow : hypovolemia, vasoconstriction, cardiogenic, shock, substrates for anaerobic metabolism delivered

glycolytic pathway

causes for ischemia

hypovolemia

infarction

vasoconstriction

shock

loss of oxygen + loss of substrates

mechanisms of cell injury

interference with substrates or enzymes:

glycolisis

citric acid cycle

oxidative phosphorylation

Produce enzymes or molecules that degrade cell components

phospholipases

free radicals

list 3 pathogenesis of glycogen accumulation

prolonged severe hyperglycemia can cause

glycogen accumulation

which of the following calcification is seen in areas of necrosis

which of the following causes toxicosis calcification

causes of metastatic calcification