Cell Injury I

what is the focus of pathology?

structural, biochemical, & functional changes in cells, tissues, & organs

what is the goal of pathology?

find underlying mechanisms of disease

what are the various techniques used in pathology?

molecular, microbiologic, immunologic, & morphologic

what are the goals of pathology?

• explain signs & symptoms

• provide rational bias for diagnosis, care, therapy

what is pathology's role in medicine?

• bridge between basic sciences & clinical medicine

• scientific foundation for all of medicine

describe the difference between general pathology and systemic pathology

general: study cell/tissue response to abnormal stimuli & inherited defects (disease mechanisms)

systemic: examine disease effects on organs & tissues (organ-specific disorders)

what are the 4 aspects that form the core of pathology?

1. etiology

2. pathogenesis

3. molecular & morphologic changes

4. clinical manifestations

what is cellular adaptation?

• reversible responses to physiologic changes & pathologic stimuli

• reversible changes in cell size, cell number, cell phenotype, metabolic activity, function

what is an example of a physiologic stimuli that causes cellular adaptation?

exercise & pregnancy

what is an example of a pathologic stimuli that cause cellular adaptation?

stress & injury

what are the 4 types of cellular adaptations?

hypertrophy, hyperplasia, atrophy, metaplasia

what is hypertrophy?

increase cell size & function

what is hyperplasia?

increase cell number

what is atrophy?

decrease cell size (and metabolic activity)

what is metaplasia?

change cell phenotype

what happens if the stimulus that causes cellular adaptation is removed?

cells return to normal state w/o permanent damage

what happens if a cell cannot adapt to stress?

cellular injury

what are the 2 possible outcomes of irreversible cell injury?

necrosis or apoptosis (cell death)

what stimulus causes cellular adaptation to occur?

environmental changes

what changes can cellular adaptation involve depending on stress type?

changes in cellular growth, size, & differentiation

what are the mechanisms of cellular adaptation?

• up or down regulation of specific cellular receptors

• induce new protein synthesis

• switch protein production or overproduce specific protein

at what levels can cellular adaptation occur?

receptor binding, signal transduction, protein transcription/translation/export

what are labile cells? give some examples

continuously dividing cells

• GI tract & respiratory tract epithelial cells

• bone marrow stem cells

what are stable cells? give some examples

quiescent cells - normally in G0 phase - that only divide when stimulated

• parenchymal cells: liver, kidney, pancreas

  • mesenchymal cells: bone, cartilage, fibroblasts

what are permanent cells? give some examples

non-dividing cells in postnatal life that CANNOT regenerate after injury

• neurons

• skeletal muscle cells

• cardiac muscle cells

what happens when permanent cells die?

they are replaced by fibrous tissue which is nonfunctional

what is hyperplasia and what happens to an organ or tissue because of it?

increase in number of cells in organ or tissue - organ/tissue volume inreases

in what type of tissue can hyperplasia occur?

tissues with cells capable of dividing

what can hyperplasia occur with?

hypertrophy

what are the 2 types of hyperplasia?

physiological - hormonal changes

pathological - endometrial hyperplasia

what are the 2 mechanisms of hyperplasia?

1. growth factor-driven proliferation of mature cells

2. increased output of new cells from tissue stem cells

how does liver regeneration occur after a partial hepatectomy?

live produce new growth factors that engage receptors on surviving cells and trigger signaling pathways that stimulate cell proliferation

what happens if mature liver cells cannot proliferate?

regeneration occurs via intrahepatic stem cells instead

what are the 2 types of physiologic hyperplasia?

1. hormonal hyperplasia

2. compensatory hyperplasia

what is hormonal hyperplasia?

hyperplasia that occurs in response to hormonal stimulation

what is compensatory hyperplasia?

hyperplasia that occurs to restore tissue mass after injury or loss

what are 2 causes of pathological hyperplasia?

1. excessive hormonal stimulation

2. effects of growth factors on target cells

why is pathological hyperplasia clinically significant?

• creates fertile ground for cancer development

• pts w endometrial hyperplasia have increased risk of developing endometrial cancer

what is hypertrophy and what happens to an organ because of it?

increase in cell size - organ size increases

what is the mechanisms of hypertrophy?

increased production of cellular protein & nuclear DNA

• phenotypic alteration of myocytes

• re-expression of embryonic developmental genes

• switch in contractile protein expression

what happens during the molecular pathogenesis of hypertrophy?

Mechanical sensors, growth factors, and vasoactive agents activate signal transduction pathways and transcription factors that increase muscle protein synthesis

in what cell types can hypertrophy occur?

non-dividing cells, esp skeletal & cardiac muscle

what can hypertrophy occur with?

hyperplasia in dividing cells

what are the triggers of hypertrophy?

mechanical stretch & trophic signals

what are the 2 types of hypertrophy?

physiologic - muscle growth w exercise

pathologic - ventricular hypertrophy from hypertention

what are the causes of hypertrophy?

• increased functional demand

• hormonal stimulation

what is physiologic hypertrophy driven by?

hormonal stimulation

what is an example of pathologic hypertrophy?

left ventricular hypertrophy from hypertension or valvular disease

what does long-term hypertrophy lead to and why?

cardiac failure - due to muscle degeneration

what is atrophy and what happens to an organ because of it?

cell size shrinks due to loss of cell substance - decreased organ size

what are the biochemical mechanisms of atrophy?

decrease protein synthesis & increase protein degradation

what cellular process is involved in atrophy to reduce nutrient demand?

autophagy

what is autophagy?

self eating process to reduce nutrient demand and break down cellular components (atrophy)

what accumulates during autophagy and what does it cause?

residual bodies (lipofuscin granules) that cause brown discoloration of tissues

what is brown atrophy?

brown discoloration of tissues caused by residual bodies of lipofuscin granules in autophagy

what are the main causes atrophy?

• disuse, denervation, diminished blood supply

• inadequate nutrition

• loss of endocrine stimulation

• senile

• pressure

what are the 2 types of atrophy?

physiologic atrophy - normal development (notochord)

pathologic atrophy - from disease or disuse; can be localized or generalized

what is metaplasia and give an example?

reversible change where one adult cell type is replaced by another adult cell type - tissue changes from columnar to squamous

why does metaplasia occur?

to adapt tissue to stronger and more stress-resistant cell type

• replace sensitive tissue w stronger tissue

is metaplasia reversible?

yes

what is the mechanism of metaplasia?

genetic reprogramming of stem cells so they differentiate along different pathways to produce sturdier cell type

what mediators can contribute to metaplasia?

growth factors, cytokines, & extracellular matrix components

is metaplasia considered a normal physiologic process?

no, and it may be the first step towards neoplasia

what are the 2 types of metaplasia?

epithelial metaplasia

connective tissue (mesenchymal) metaplasia

what are the 2 types of epithelial metaplasia?

squamous metaplasia - columnar → squamous

columnar metaplasia - squamous → columnar

what is connective tissue (mesenchymal) metaplasia?

formation of cartilage, bone, or adipose tissue in abnormal locations

give an example of connective tissue (mesenchymal) metaplasia

myositis ossificans - bone form in muscle tissue

what is the survival trade-off of metaplasia?

metaplastic cells adapt to survive in adverse environments, but lose original protective functions

what can persistent stress on metaplasia tissue cause?

malignancy risk - cancerous transformation of epithelium like squamous cell carcinoma of lung