Disorders of Development and Growth

This section will deal with abnormalities that occur in cellular growth and development of the individual form conception to death. We will discuss these changes under the following headings.

Disorders of development

Before going through details of this section we have to know some definitions.

Anlage

It is a mass of primitive cells from which an organ develops.

Teratology

It is the science which dealing with the study of congenital malformations, which occur during intrauterine life and present at birth. It includes anomalies and monsters.

1. Anomalies

It is the intrauterine disturbance in development, which involve organ or a portion of an organ.

1. Agenesis

It is a complete absence of organ due to the failure of anlage development in embryo. If agenesis occurs in vital organs as brain (an-encephaly) fetal development may not proceed and abortion or resorption occurs. Moreover, pregnancy complete in those involved paired organs as kidneys and non-vital organs as legs ( Fig. 1 ).

2. Aplasia

It is complete absence of organ. It distinguished from agenesis by presence of undeveloped anlage or its vascular connection can be identified as an-opthalmia (absence of one or both eyes).

3. Atresia

It means absence or closure of a normal opening as atresia ani which mean absence of anus (Fig. 2).

4. Dysgenesis

Abnormal structure of an organ resulted from abnormal differentiation of anlage. For example, in renal dysgenesis a mass of tissue composed of abnormal epithelium lined cysts, cartilage is formed instead of kidney.

5. Hypoplasia

It is the failure of an organ or part to obtain full mature size (Figs 3 & 4).

Figure 1: Amelia Horse showing absence of fore limb.

Figure 2: Atresia ani in piglet.

Figure 3: Brain showing cerebral hypoplasia

Figure 4: Brain showing cerebral hypoplasia H&E.

6. Displacements during development

A) Displacement of organs

Dextrocardia which means presence of heart in right side.

Ectopia cordis cervicals (displacement of the heart into the neck).

B. Displacement of tissue

Dermoid cyst

It is a cyst containing skin, hair or teeth. It is usually occurs in subcutaneous connective tissues. The cyst cavity is lined by stratified squamous epithelium with skin appendages filled with sebaceous debris and mated hair (Fig. 5).

Epidermoid cyst

It is the implantation of part of epidermis into the deeper subcutaneous tissue as a result of trauma.

Odontoid cyst

It composed of dental and cement or rudimentary teethes in a connective tissue stroma.

N.B.: Teratoma: It is a true neoplasm. It composed of multiple displaced ad also neoplastic tissue within an individual. At least two of the tissue is foreign to the tissues where it is found (Figs 6 & 7).

7. Persistence of fetal structure

This includes foramen ovalae, ductus arteriosus (Fig. 8), etc.

Figure 5: Dermoid cyst.

Figure 6:Ovary teratoma.

Figure 7: Ovary teratoma. The ovarian tissue containing cartilage. H&E

Figure 8: Patent ductus arteriosis

8. Persistence of fetal structure

As Cyclopia (Fig. 9) and renal arcuatus

9. Fissure on the median line

As Cranioschisis, chelioschisis, and Schistosomus (Fig. 10).

10. Fusion of sexual characters

Hermaphrodite:

An individual having both testicular and ovarian tissue (Fig. 11).

Pseudo-hermaphrodite

An animal having either testicular or ovarian tissue but having also either the opposite unisexual or bisexual development of external genitalia (Fig. 12).

Freemartin

It occurs in bovine have twin pregnancy sharing the same placenta. The female calf (share same placenta with male) showed arrested development of sex organs. The explanation is based upon that the sex hormones appear earlier in male fetus than in female and travel through common fetal circulation and depresses the growth of female genital tract (Fig. 13).

Figure 9: Lamb showing Cyclopia.

Figure 10: Goat showing Schistosomus reflexus.

Figure 11: Goat urogenital system showing true hermaphrodite.

Figure 12: Pseudo male hermaphrodite.

Figure 13: Urogenital tract of freemartin calf.

II. Monsters

It is a disturbance of development that involves several organs and causes great distortion of the individual.

Classification

a. Twins entirely separate

These twins are in a single chorion. One twin is will developed, the other is malformed.

b. Twin united

1.  Anterior twining: the anterior part is double (Fig. 14).

2.  Posterior twining: the posterior part is double (Fig. 15).

Causes of fetal abnormalities

• In most instance, the exact cause is unknown.

• Genetic disorders (mutation).

• External agent caused abnormal development of fetus which aren’t inherited:

a. Teratogenic viral as Rubella.

b. Drugs as diethylstilbestrol (Des).

c. Alcohol and cigarette smoking (retardation of growth).

d. Ionizing radiation.

e. Mechanical trauma.

f. Nutritional deficiency.

Disorders of cellular growth, differentiation and maturation

I. Abnormal growth

Abnormal cellular growth may result in either decrease or increase in the mass of the involved tissue.

1. Atrophy

Atrophy is a shrinking or reduction of a mature organ or tissue to less than its normal size, resulting from decrease in size of individual cells (quantitative atrophy) or number of cells (numerical atrophy) composing the tissue.

Causes of atrophy

A. Physiological atrophy

It is observed in thymus of animals approaching maturity and mammary gland at end of lactation.

B. Pathological atrophy

1. Atrophy of disuse

Atrophy of immobilized skeletal muscle and bone, as when a fractured limb put in a cast.

2. Denervation atrophy

Skeletal muscle is developed on its nerve supply for normal function and structure. Damage to the lower motor neuron at any part between cell body in the spinal cord and the motor end plate leads to rapid atrophy of the muscle fibers supplied by the nerve.

3. Atrophy due to loss of trophic hormones

The endometrium, breast and many endocrine glands are depend on trophic hormones for normal cellular growth.

Examples: include atrophy of uterus after ovariectomy and atrophy of prostate after orchiectomy.

4. Atrophy due to lack of nutrients

It causes almost atrophy of parenchymal and muscular tissue.

5. Senile atrophy

Cell loss is one of the morphological changes of the aging process. It is most apparent in tissues populated by permanent cells, as brain and heart.

6. Inadequate blood supply

It results in quantitative and numerical atrophy as in case of chronic venous congestion of liver or gradual vascular obstruction.

7. Pressure atrophy

As in case of large encapsulated benign tumor.

Gross appearance

Organ is smaller than normal and lighter. A translucent gelatinous material replaces adipose tissue.

Capsule may be wrinkled.

Microscopic appearance

1. Decrease in the size or number of cells or both of them

2. Increase in the amount of connective tissue stroma.

3. Nuclei seem to be more numerous than normal with more lipochrome pigments in cytoplasm

2. Hypertrophy

It is increase in size of tissue due to increase in size of cells.

It occur in tissue with permanent cells, in which a demand for increased metabolic activity cannot be met through cell multiplication.

Hypertrophy of most tissues and organs results from a combination of cellular hypertrophy and hyperplasia.

Microscopic appearance

It represented by increase amount of cytoplasm and cell organelles.

Macroscopic appearance

The organ is enlarged (Fig. 16).

Classification

Compensatory or adaptive hypertrophy

Physiological as enlargement of skeletal muscles as a result of repeated exercise.

Pathological as a result of loss of one kidney for any reason results in gradual enlargement of remaining kidney to compensate loss of function of missing organ.

Also, myocardial hypertrophy with hypertension and valvular diseases.

Hormonal hypertrophy

This most often physiologic phenomenon as increase size of testes in birds and some mammals during mating season.

Significance

Hypertrophy is adaptive mechanism and a response for increased function.

Occasionally, the enlarges organ may constitute a mechanical hindrance to some other function as in enlargement of heart muscle that causes distortion of the valves and heart failure resulting from inadequate blood supply.

3. Hyperplasia

It is an increase in size of a tissue due to increased numbers of component cells.

It is limited to organ and tissue in which the cells retain the capacity to divide. It may be nodular or diffuse.

It is limited in amount and terminates when stimulus that evokes it ceased.

Classification

1. Compensatory hyperplasia

It may be physiological (occurs during development and maturation) or pathological as.

Erythroid hyperplasia in case of loss of blood or reduced atmospheric oxygen tension.

Lymphoid hyperplasia in response to infection (Fig. 17).

Hyperplasia of biliary epithelium in hepatic coccidiosis in rabbit.

2. Hormonal hyperplasia

Physiological as hyperplasia of mammary gland or uterus associated with puberty or pregnancy.

Pathologic as in case of thyroid hyperplasia (goiter) or cystic hyperplasia of uterus associated with ovarian malfunction.

Gross and microscopic appearance

It vary with tissue affected and the case.

The affected organ increase in size and weight.

Hyperplasia of glandular organs show increase in the high of acinar epithelium and, at the same time, an increase in the number of its cells (Figs18 & 19).

Figure 14: Calf showing anterior twining (Dicephalus bicollis).

Figure 15: Piglet showing posterior twining (Dipagus parasiticus).

Figure 16: Gross picture of the heart showing hypertrophy of the ventricular wall.

Figure 17: Histological section of Lymphoid hyperplasia. H&E.

Figure 18: Liver showing hyperplasia of bile duct. The hyperplastic epithelium showing newly formed ductules. H&E.

The epithelium lining become wavy, folded and send papillary projection into the lumen (Fig. 20).

In the epidermis hyperplasia take the form of increased thickness of prickle cell layer (acanthosis) or of the cornified layer (hyperkeratosis) (Fig. 21).

Figure 19: Liver showing hyperplasia of bile duct. The hyperplastic epithelium showing newly formed ductules. H&E.

Figure 20: Histological section of a bronchiole showing epithelial hyperplasia. The epithelium lining become wavy, folded and send papillary projection into the lumen

Figure 21:Skin showing epidermal hyperplasia take the form of increased thickness of prickle cell layer. H&E.

Hyperplastic cells usually have an increased nuclear to cytoplasmic ratio.

Abnormal growths principally involving differentiation

1.  Metaplasia

It is an abnormality of cellular differentiation in which one type of mature cell is replaced by a different type of mature cell of same germinal layer

Classification

1. Epithelial metaplasia

The most common type is squamous metaplasia (Figs 22& 23). It is common in the endocervix and bronchial mucosa.

  Causes

1. Mild irritant over long period.

2. Vitamin A deficiency

3. Senility as change of the simple columnar epithelium of endometrium into squamous epithelium.

2. Connective tissue metaplasia

Fibrous tissue changes to cartilage and bone (Figs 24& 25).

Figure 22: Histological section of a bronchiole showing epithelial metaplasia.  The simple columnar epithelium changed to squamous epithelium. H&E

Figure 23: Histological section of a bronchiole showing epithelial metaplasia.

Figure 24: Osseous metaplasia in fibrous connective tissue nodules around Spirocerca lupi. H&E.

Figure 25:  Spleen showing osseous metaplasia. H&E.

Causes

Chronic irritation.

Hormonal disturbances.

2. Dysplasia

It refers to alteration in shape, size and organization. It may occur during fetal development or in adult tissues. Dysplasia characterized microscopically by abnormal orientation of cells, variation in size and shape of cells and nuclei. Moreover, it shows increase nuclear to cytoplasmic ratio. It is usually is used with reference with epithelium. Epithelium dysplasia is a premalignant lesion associated with an increase risk of neoplasia.

Difference between dysplasia and cancer

1. Lack of invasiveness

2. Reversibility

Differences between neoplasia and hyperplasia