Growth Adaptations Pathology Study Guide

GROWTH ADAPTATIONS
How the microenvironment shapes the immune response and vice versa. We hypothesize that radiation induces damage to tissue resident cells, e.g., endothelial and epithelial lung cells, mesenchymal stem cells (MSC) as well as in resident immune cells. The resulting tissue damage can initiate stress responses or cell death with subsequent release of cytokines/chemokines and damage-associated molecular patterns (DAMPs). This initial damage response leads to the recruitment and activation of diverse immune cells to the lung, among them lymphocytes. Further activation, proliferation of these cells, and secretion of cytokines shape the pulmonary micromilieu toward inflammation and—if this response is too excessive—to the development of severe pneumonitis. Late chronic mitotic cell death and subsequent tissue hypoxia lead to the release of DAMPs and cytokines/chemokines from resident cells thereby altering the micromilieu in the lung. These environmental changes impact on the immune cells present in the lung tissue and promote an altered cytokine release of immune cells. Finally, epithelial-mesenchymal-transition, endothelial-mesenchymal-transition, mesenchymal stem cell differentiation, and the altered environment contribute to the induction of activated myofibroblasts, collagen deposition, and fibrosis. The Role of Lymphocytes in Radiotherapy-Induced Adverse Late Effects in the Lung. Frontiers in Immunology. Not Altered. CC.

Growth Adaptations

Growth Adaptations Pathology Video

An organ ideally exists in homeostasis with the physiologic stress that it is exposed to.  

Changes in the amount of stress may result in growth adaptations.

Changes in the stress may be:

  • Increased stress
  • Decreased stress
  • Different type of stress 

An increase in stress causes organs to grow larger.

A decrease in stress causes an organ to shrink.

A different type of stress may result in a dependent fashion.

Cellular Responses to Stress
ARTDs/PARPs regulate cellular processes that viruses manipulate. ARTDs are involved in the regulation of multiple cellular stress responses. Virus infection is inherently stressful for the cell and often induces cellular stress responses in the course of replication. Stress-related pathways that are known to overlap between virus infection and ARTD activity are highlighted above. We have emphasized ARTD15’s role in PERK activation [10] and ARTD13’s ability to regulate RNA transcripts through direct (facilitating degradation of RNA [11,12]) and indirect (contributing to RISC inactivation [9]) mechanisms, while contributing to interferon production in response to molecular signatures of viral RNA [9,13]. We also indicate that multiple members of the ARTD family are interferon-stimulated genes (ISGs) [14,15], localize to stress granules [8], and contribute to DNA repair and overall metabolic changes in the cell [2,6,7]. Virus-Host Interactions and the ARTD/PARP Family of Enzymes. Kuny CV, Sullivan CS – PLoS pathogens (2016). Not Altered. CC.

Atrophy

Atrophy means to waste away, especially as a result of the degeneration of cells.

Atrophy may be due to a decrease in cell size or a decrease in cell number. 

A decrease in stress may lead to atrophy.

Examples of atrophy include:

  • A decrease in skeletal muscle size due to lack of use due to being in a cast after a broken bone
  • Vaginal atrophy after menopause due to decreased estrogen

Examples of conditions that may lead to atrophy include:

  • Lack of use
  • Lack of exercise
  • Lack of hormonal stimulation
  • Lack of blood flow
  • Lack of nutrients

A decrease in cell number occurs via apoptosis.

A decrease in cell size occurs via ubiquitin-proteasome mediated degradation of the cytoskeleton and autophagy of cellular components.

In ubiquitin-proteasome degradation, intermediate filaments of the cytoskeleton are marked for degradation by ubiquitin and destroyed by proteasomes.

Autophagy of cellular components involves generation of autophagic vacuoles that fuse with lysosomes that have hydrolytic enzymes that chemically destroy cellular components.

Poliomyelitis
Poliomyelitis. Man on street with atrophy and paralysis of the right leg and foot due to polio. Photo Credit: Content Providers(s): CDC/NIP/ Barbara Rice – Not altered. Public domain.

Hyperplasia

Hyperplasia is an increase in cell number. 

Hyperplasia involves producing new cells from stem cells via cell division.

Endometrial Hyperplasia
Endometrial Hyperplasia. Histopathology of complex hyperplasia with atypia: Closely packed endometrial glands with sparse intervening stroma and stratification of the lining epithelium. Epithelial cells show cytological atypia with high nucleocytoplasmic ratio, irregular clumping of nuclear chromatin, and mitotic figures. Shalinee Rao, Sandhya Sundaram, Raghavan Narasimhan – Not altered. CC BY 2.0

Hypertrophy

Hypertrophy is an increase in cell size. 

Hypertrophy occurs when there is an increase in the size of muscle cells.

Hyperplasia occurs when there is an increased number of muscle cells.

Hypertrophy occurs when genes are activated, proteins are synthesized, and organelles are produced.

Hypertrophy and hyperplasia usually occur together.

Please note that permanent tissues generally do not make new cells and only undergo hypertrophy.

Examples of permanent cells include: 

  • Cardiac muscle
  • Skeletal muscle
  • Nerve

Hypertrophy, not hyperplasia, occurs in cardiac myocytes in response to systemic hypertension.

Hyperplasia can progress to dysplasia and, continue to progress to cancer if left unchecked.

Endometrial hyperplasia is an example of hyperplasia that may progress to dysplasia.

Hyperplasia
Hyperplasia. Simple illustration showing the difference between hyperplasia and hypertrophy. Schwarze Melancholie. Not altered. CC BY-SA 3.0

Metaplasia

Metaplasia is the transformation of one differentiated cell type into another type of differentiated cell.

A change in stress on an organ my cause metaplasia.

Metaplasia most commonly involves changing from one type of surface epithelial cell to another.

Examples of surface epithelial cells include:

  • Squamous cells
  • Urothelial cells
  • Columnar cells

Metaplasia is not cancer.

Metaplasia may progress to dysplasia.

Dysplasia is not cancer.

Metaplasia may progress to dysplasia, and dysplasia may progress to cancer.

Metaplastic cells are better suited to withstand the stress that caused the change in cell type.

The classic example of metaplasia is Barrett’s esophagus.

The esophagus is usually lined by nonkeratinized squamous epithelium cells, which are suited to handle the stress and friction associated with swallowing food.

Gastric acid reflux from the stomach can cause metaplasia of the nonkeratinized squamous epithelium cells of the esophagus, changing them to non-ciliated columnar cells with interspersed goblet cells which is the histologic definition of Barrett’s esophagus.

Metaplasia occurs by reprogramming stem cells to produces the new cell type that can handle the increased stress.

Metaplasia is reversible.

Metaplasia can be reversed by removing the stress that is causing the metaplastic change.

Metaplasia of Barrett’s esophagus can be reversed by stopping the acid reflux.

Continued presence of metaplasia may lead to dysplasia, which can further progress to cancer.

The continued presence of metaplasia that causes Barrett’s esophagus may progress to dysplasia which may potentially progress to adenocarcinoma of the esophagus.

Keratomalacia is another classic form of metaplasia is due to vitamin A deficiency.

Vitamin A is needed for the development of specialized epithelial surfaces, such as the conjunctival surface covering the eyes.

Vitamin A deficiency causes the thin conjunctival epithelium to undergo metaplasia into stratifying keratinizing squamous cells, which is known as keratomalacia.

Myositis ossificans is another type of metaplasia, in which connective tissues can also undergo meta­plasia.

Myositis ossificans is the classical example of connective tissue metaplasia, which results in muscle turning into bone when healing from a trauma. 

Esophagus Pathology
Esophagus Pathology. Histopathology of Barrett’s esophagus, showing intestinalized epithelium with goblet cells, as opposed to normal stratified squamous epithelium of the esophagus, and pseudostratified columnar epithelium of the fundus of the stomach. The submucosa displays an infiltrate including lymphocytes and plasma cells, constituting an underlying chronic inflammation. The area between the stratified and the intestinalized epithelium displays reactive changes, but there is no secondary dysplasia in this case. H&E stain. Mikael Häggström, M.D. Not altered. CC0

Dysplasia

Dysplasia is disordered cell growth. 

Dysplasia is usually used to describe precancerous cells. 

Cervical intraepithelial neoplasia (CIN) represents dysplasia. 

Cervical intraepithelial neoplasia (CIN) is a precursor lesion to cervical cancer.

Dysplasia often arises from long standing pathologic hyperplasia such as endometrial hyperplasia (which may progress to endometrial adenocarcinoma).

Dysplasia is reversible.

Cancer is not reversible.  

Barrett’s esophagus (metaplasia) is reversible.

Barrett’s esophagus with dysplastic features is reversible.

Esophageal adenocarcinoma is not reversible.

Spectrum of SILCervical Dysplasia
Cervical Dysplasia. Ed Uthman. Not altered. CC BY 2.0

Aplasia

Aplasia is the failure of cell production (agenesis) during embryogenesis. 

Classic examples of agenesis include:

  • Anodontia – certain teeth do not develop
  • Agenesis of the corpus callosum – corpus callosum does not develop
  • Agenesis of the gallbladder – gall bladder does not develop
  • Aglossia – tongue does not develop
  • Agnathia – jaw does not develop
  • Amelia – arms and/or legs do not develop
  • Ear agenesis – ears do not develop
  • Eye agenesis – eyes do not develop
  • Mullerian agenesis – uterus and parts of the vagina do not develop
  • Penile agenesis – penis does not develop
Malformations and Developmental Disorders of the Central Nervous System
A 1-year-old boy. Clinical symptoms: psychomotor retardation. MR image. (A). T1-weighted image, axial plane. (B) T2-weighted image, sagittal plane. (C) T1-weighted image, axial plane. Heterotopic gray matter bilaterally in parietal regions (asterisk), pachygyria, agenesis of the septum pellucidum, hypoplasia of the corpus callosum.Clinical and morphological aspects of gray matter heterotopia type developmental malformations. Zając-Mnich M, Kostkiewicz A, Guz W, Dziurzyńska-Białek E, Solińska A, Stopa J, Kucharska-Miąsik I – Polish journal of radiology / Polish Medical Society of Radiology (2014). Not Altered. CC.

Hypoplasia

Hypoplasia is the decrease in cell production during embryogenesis.

Hypoplasia results in small organs. 

Classic examples of hypoplasia include:

  • Streak ovaries in Turner syndrome
  • Small testes in Klinefelter syndrome
  • Small thymus in DiGeorge syndrome
  • Small lungs as a result of oligohydramnios
  • Small ears and fingers in Harlequin-type ichthyosis
Turner Syndrome
Classical phenotype of a patient (10 years old) with Turner syndrome. Clinical and genetic characteristics in a group of 45 patients with Turner syndrome (monocentric study). Therapeutics and Clinical Risk Management. Not Altered. CC.
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