Cell Injury 1

Pathology focuses on

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

• underlying mechanisms of disease

goals of pathology

• explains signs & symptom

• provide a rational basis for diagnosis, care, & therapy

general pathology

studies cell/tissue responses to abnormal stimuli & inherited defects; focuses on basic disease mechanisms

systemic pathology

examines disease effects on specific organs & tissues; focuses on organ-specific disorders

4 aspects of a disease process that form the core of pathology

1) cause (etiology)

2) mechanisms of its development (pathogenesis)

3) biochemical & structural alterations induced in the cells & organs of the body (molecular & morphologic changes)

4) functional consequences of these changes (clinical manifestations)

cellular adaptations are reversible responses to

• physiologic changes (pregnancy)

• pathologic stimuli (stress, injury)

cellular adaptations are reversible changes in

• cell size

• cell number

• cell phenotype

• metabolic activity

• function

mechanisms of cellular adaptation can proceed by multiple mechanisms including

• up/down regulation of specific cellular receptors

• induction of new protein synthesi

• switching protein production or overproducing a specific protein

adaptation can occur at various levels

• receptor binding

• signal transduction

• protein transcription, translation, or export

labile cells

continuously dividing cells (epithelial cells of the GIT, respiratory tract)

stable cells

• quiescent cells (normally in G0 phase)

• divide only when stimulated

• examples: parenchymal cells & mesenchymal cells

permanent cells

• non-dividing in postnatal life

• unable to regenerate after injury

• examples: neurons, skeletal muscle cells, cardiac muscle cells

hyperplasia

• increase in # of cells in an organ/tissue

• usually leads to increased volume of the affected organ/tissue

hyperplasia often occurs together w/….

hypertrophy

types of hyperplasia

• physiological (hormonal changes)

• pathological (endometrial hyperplasia)

hyperplasia occurs due to

• growth factor-driven proliferation of mature cells

• increased output of new cells from tissue stem cells

• ex. liver regeneration

hormonal hyperplasia

occurs in response to hormonal stimulation (glandular epithelium of female breast during puberty, pregnancy, lactation)

compensatory hyperplasia

occurs to restore tissue mass after injury or loss (hepatocyte proliferation after partial hepatectomy)

causes of pathological hyperplasia

• excessive hormonal stimulation

• effects of growth factors on target cells

clinical significance of pathological hyperplasia

• pathologic hyperplasia creates a fertile ground for cancer development

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

hypertrophy

increase in cell size leading to increased organ size

mechanisms of hypertrophy

• due to synthesis of more structural components

• involves phenotypic alteration of individual myocytes

• re-expression of embryonic/early developmental genes

• switch in contractile protein expression occurs

• triggers include mechanical stretch & trophic signals

cell types involved in hypertrophy

• occurs mainly in non-dividing cells (skeletal muscle, cardiac muscle)

  • may occur w/ hyperplasia in dividing cells

causes of hypertrophy

• increased functional demand

• hormonal stimulation

physiologic hypertrophy

driven by hormonal stimulation (growth of the uterus during pregnancy, lactacting breast)

pathologic hypertrophy

• cardiac hypertrophy from hypertension or valvular disease

• long-term hypertrophy → cardiac failure due to muscle degeneration

adaptive hypertrophy

skeletal muscle hypertrophy from exercise or labor

atrophy

shrinkage in cell size due to loss of cell substance → results in decreased organ size

atrophy causes

• decreased workload

• loss of innervations

• diminished blood supply

• inadequate nutrition

• loss of endocrine stimulation

• senile atrophy

• pressure atrophy

metaplasia

reversible change where one adult cell type (epithelial or mesenchymal is replaced by another adult cell type

adaptive mechanism of metaplasia

protects tissues by substituting sensitive cells w/ cells more resistant to stress

metaplasia types

• epithelial metaplasia (most common)

• columnar to squamous (squamous metaplasia; respiratory epithelium of bronchi in chronic smokers)

• squamous to columnar epithelium (columnar metaplasia; Barret esophagitis)

connective tissue (mesenchymal) metaplasia

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

metaplastic cells adapt to survive in adverse environments but may

lost their original protective functions

persistent stress or stimuli promoting metaplasia may lead to

cancerous transformation of epithelium

A 60-year-old man with long-standing hypertension is found to have concentric left ventricular hypertrophy on echocardiogram. Which of the following best explains the cellular mechanism underlying this adaptation?

Increased synthesis of structural proteins

A 52-year-old woman is diagnosed with endometrial hyperplasia due to unopposed estrogen stimulation. This form of cellular adaptation increases her risk of developing which of the following?

Endometrial carcinoma

A 55-year-old man with a 30-year history of smoking undergoes bronchoscopy. Biopsy of bronchial mucosa reveals replacement of normal pseudostratified columnar epithelium with stratified squamous epithelium. Which of the following statements is most accurate about this finding?

It is a reversible process in response to chronic irritation