Cellular adaptation

Hyperplasia is an increase in cell number, whereas metaplasia is the replacement of one adult cell type by another adult cell type. Hyperplasia occurs when there is increased trophic stimulation (e.g., hormones, growth factors), increased functional demand, or persistent cell injury. Only labile and stable cells undergo hyperplasia; labile cells have stern cells that frequently divide, and stable cells have resting cells that are stimulated to enter the cell cycle.

The presence of increased goblet cells in the mainstem bronchus of a smoker is an example of hyperplasia because goblet cells are normally present in this area. However, their presence in the terminal bronchiole or gastric mucosa, where they are not normally found, is an example of metaplasia. Squamous epithelium in the bladder of a patient with Schistosoma haernatobium is an example of metaplasia because the epithelium of a normal bladder is transitional.

Irritation from the eggs of the schistosomes induces squamous metaplasia and the potential for dysplasia and squamous carcinoma. A distal esophagus with glandular epithelium intermixed with squamous epithelium is an example of Barrett’s esophagus. Chronic acid injury to the distal esophagus from gastroesophageal reflux stimulates the formation of mucous secreting glandular epithelium, which is a type of glandular metaplasia and predisposes the patient to adenocarcinoma. Goblet and Paneth cells in the glands of the gastric mucosa are called intestinal metaplasia and are commonly seen in chronic atrophic gastritis of the body and fundus (type A) or pylorus and antrum (type B). It is a precursor lesion of adenocarcinoma of the stomach.

Squamous epithelium in the mains tern bronchus of a smoker is squamous metaplasia because the normal epithelium is pseudostratified, ciliated, and columnar. The squamous epithelium is a reaction to injury induced by cigarette smoke. It predisposes the patient to squamous dysplasia and carcinoma.

Chronic irritation

Metaplasia is a reversible change in which one adult cell type is replaced by another adult cell type.

In this type of cellular adaptation, a cell type sensitive to particular stress is replaced by another cell type better able to withstand the adverse environment.

Metaplasia is commonly seen in the epithelial surfaces of the bronchial tree secondary to chronic irritation of cigarette smoke. Metaplasia may also be seen in areas of long-standing, chronic infections.

Barrett’s esophagus refers to the metaplastic change of distal esophageal mucosa from normal squamous epithelium to columnar epithelium, in response to chronic gastroesophageal reflux.

The most common type of metaplasia is intestinal type of metaplasia and presence of intestinal goblet cell is the hallmark of intestinal metaplasia.

Stricture formation and peptic ulceration of columnar lined epithelium of esophagus is common complication of barrett’s esophagus.

Barrett’s esophagus can be classified into long segment( involvement of >3 cm of esophagus) and short segment disease ( involvement of < 3 cm of esophagus).

Long segment disease carries more risk for adenocarcinoma.

Barrett’s esophagus is associated with sliding hernia not with paraesophageal hernia.
 

Ref: Robbins 8/e, Page 770; Bailey & Love 25/e, Page 1022.

• Chromosome deletions (particularly 11p, 13q, 17p, and 3p)
• Tumor suppressor gene mutations (p53, Hap-1, ErbAb, etc)
• High-level expression of both growth factor genes (insulinlike and transferrinlike growth factors)
• Epidermal growth factor receptors (HER2/neu,EGFR1, etc)
• Protooncogenes (c-, N- and L-myc; H-, N-, and K-ras; and c-myb)
• Vitamin A deficiency
• Air pollution
• Exposure to arsenic, cadmium, chromium, ether, and formaldehyde
• Employment as bakers, cooks, construction workers, cosmetologists, leather workers, pitchblende miners, printers, rubber workers, and pottery workers 

During pregnancy, the myometrium goes through a period of extensive growth involving both hyperplasia (increasing the number of smooth muscle cells), cell hypertrophy, and increased collagen production by the muscle cells, which strengthens the uterine wall.

This well-developed uterine myometrium contracts very forcefully during parturition to expel the infant from the uterus.

After pregnancy, uterine smooth muscle cells shrink and many undergo apoptosis, with removal of unneeded collagen, and the uterus returns almost to its prepregnancy size.

Ref: Mescher A.L. (2013). Chapter 22. The Female Reproductive System. In A.L. Mescher (Ed), Junqueira’s Basic Histology, 13e.

Ans. is ‘c’ i.e., Increase in cell number

Hvperplasia

o Hyperplasia is an increase in the number of cells without increase in size in an organ or tissue (by contrast hypertrophy refers to an increase in the size of cells).

o Hyperplasia takes place if the cellular population is capable of synthesizing DNA, thus permitting mitotic division i.e., hyperplasia involves cell division (by contrast hypertrophy involves cell enlargement without cell division). o Hyperplasia can be physiological or pathological.

A. Physiological hyperplasia

o It occurs when there is increased physiological demand e.g

(a)       Hormonal —> Hyperplasia of endometrium in pregnant uterus, proliferation of the glandular epithelium of female breast at puberty and during pregnancy.

(b)       Compensatory —> Increase in tissue mass after damage or partial resection, e.g. regeneration of liver after partial hepatectomy.

B. Pathological hyperplasia

o It occurs when there is increased stimulus under certain pathologic conditions.

o Most forms of pathological hyperplasia are caused by excessive hormonal stimulation or growth factor acting on target cells, e.g., Endometrial hyperplasia due to disturbed estrogen and progesterone balance (with relative excess of estrogen) in menstural cycle.

Note : Stimulus for physiologic and pathologic hyperplasia may be the same (e.g., estrogen for endometrial hyperplasia), but in physiologic hyperplasia, the stimulus is due to normal physiologic changes of body e.g., pregnancy, while in pathologic hyperplasia the stimulus is due to certain pathologic conditions e.g., estrogen secreting ovarian tumor.

o Although pathological hyperplasia is abnormal, the process remains controlled —> Hyperplasia regresses if the hormonal stimulation is eliminated.

o It is the response to the normal regulatory control mechanisms that distinguishes benign pathological hyperplasia from Cancer, in which the growth control mechanism becomes defective.

o However, pathological hyperplasia constitues a fertile soil in which cancerous proliferation may eventually arise –> e.g., patients with endometrial hyperplasia are at increase risk of endometrial carcinoma

Mechanism of hyperplasia

o Hyperplasia is caused by increased production of growth factor or hormones that lead to production of transcription factor that turn on many cellular genes and induce cellular proliferation.

o After some type of cell loss, hyperplasia is caused not only by proliferation of cells but also by the development of new cells from stem cells —> e.g., After hepatectomy the hyperplasia is due to proliferation of the remaining hepatocytes, but in chronic hepatitis, intrahepatic stem cells play a major role in hyperplasia as the proliferative capacity of hepatocytes is compromised.

Ans. is ‘b’ i.e., Increase in cell size without increase in number

Why do some tissues undergo hypertrophy, while others undergo hyperplasia ?

o The cells that have limited capacity of proliferation (e.g., myocardial cells & skeletal muscle cells) can not increase their number, So they are not able to undergo hyperplasia. But these cells can increase in size in response to increased demand, So they can undergo hypertrophy.

o The cells capable of division (hepatocytes, renal tubular epithelial cells, smooth muscles of uterus) have both the properties, i.e., to increase the number as well as the size. So, tissues containing these cells can undergo hypertrophy or hyperplasia or both.

o For example, both hyperplasia and hypertrophy occur in endometrium of pregnant uterus.

Ans. is ‘a > c’ i.e., Uterus in pregnancy > Breast at puberty

Physiological hypertrophy and hyperplasia

* Examples of physiologically increased growth of tissues include : –

  – Skeletal muscle hypertrophy in atheletes, both in the skeletal muscle of limbs (as a response to increased muscle activity) and in left ventricle of heart (as a response to sustained outflow resistance).

  – Hyperplasia of bone marrow cells producing red blood cells in individuals living at high altitude; this is stimulated by increased production of the erythropoietin.

  – Hyperplasia of breast at puberty, and in pregnancy and lactation, under the influence of estrogen, progesterone, prolactin and human placental lactogen.

  – Hypertrophy and hyperplasia of uterine smooth muscle in pregnancy, stimulated by estrogen.

  – Thyroid hyperplasia as a consequence of the increased metabolic demand of puberty and pregnancy. For option ‘c’

  – “Hormonal hyperplasia is well illustrated by the proliferation of the glandular epithelium of the female breast at puberty and during pregnancy, usually accompanied by enlargement (hypertrophy) of the glandular epithelial cell” – 

* However, I am not sure about this statement of Robbin’s, as no other text book has mentioned that breast at puberty undergo both hyperplasia and hypertrophy.

This is one of the controversial questions wherein both answers Breast Development during puberty and Uterus Developement during Pregnancy shows both hyperplasia and hypertrophy.

However most books quote the example of Developement of Uterus during pregnancy as an example of Both Hyperplasia and Hypertrophy (Henve we will go with this option)

Ans. is ‘a’ i.e., Breast enlargement at puberty

Ans. is `b’ i.e., Increase in size of cells

Ans. is ‘c’ i.e., Necrosis