NEET MDS Lessons
General Pathology
Rickets and Osteomalacia
Rickets in growing children and osteomalacia in adults are skeletal diseases with worldwide distribution. They may result from
1. Diets deficient in calcium and vitamin D
2. Limited exposure to sunlight (in heavily veiled women, and inhabitants of northern climates with scant sunlight)
3. Renal disorders causing decreased synthesis of 1,25 (OH)2-D or phosphate depletion
4. Malabsorption disorders.
Although rickets and osteomalacia rarely occur outside high-risk groups, milder forms of vitamin D deficiency (also called vitamin D insufficiency) leading to bone loss and hip fractures are quite common in the elderly.
Whatever the basis, a deficiency of vitamin D tends to cause hypocalcemia. When hypocalcemia occurs, PTH production is increased, that ultimately leads to restoration of the serum level of calcium to near normal levels (through mobilization of Ca from bone & decrease in its tubular reabsorption) with persistent hypophosphatemia (through increase renal exretion of phosphate); so mineralization of bone is impaired or there is high bone turnover.
The basic derangement in both rickets and osteomalacia is an excess of unmineralized matrix. This complicated in rickets by derangement of endochondral bone growth.
The following sequence ensues in rickets:
1. Overgrowth of epiphyseal cartilage with distorted, irregular masses of cartilage
2. Deposition of osteoid matrix on inadequately mineralized cartilage
3. Disruption of the orderly replacement of cartilage by osteoid matrix, with enlargement and lateral expansion of the osteochondral junction
4. Microfractures and stresses of the inadequately mineralized, weak, poorly formed bone
5. Deformation of the skeleton due to the loss of structural rigidity of the developing bones
Gross features
• The gross skeletal changes depend on the severity of the disease; its duration, & the stresses to which individual bones are subjected.
• During the nonambulatory stage of infancy, the head and chest sustain the greatest stresses. The softened occipital bones may become flattened. An excess of osteoid produces frontal bossing. Deformation of the chest results from overgrowth of cartilage or osteoid tissue at the costochondral junction, producing the "rachitic rosary." The weakened metaphyseal areas of the ribs are subject to the pull of the respiratory muscles and thus bend inward, creating anterior protrusion of the sternum (pigeon breast deformity). The pelvis may become deformed.
• When an ambulating child develops rickets, deformities are likely to affect the spine, pelvis, and long bones (e.g., tibia), causing, most notably, lumbar lordosis and bowing of the legs .
• In adults the lack of vitamin D deranges the normal bone remodeling that occurs throughout life. The newly formed osteoid matrix laid down by osteoblasts is inadequately mineralized, thus producing the excess of persistent osteoid that is characteristic of osteomalacia. Although the contours of the bone are not affected, the bone is weak and vulnerable to gross fractures or microfractures, which are most likely to affect vertebral bodies and femoral necks.
Microscopic features
• The unmineralized osteoid can be visualized as a thickened layer of matrix (which stains pink in hematoxylin and eosin preparations) arranged about the more basophilic, normally mineralized trabeculae.
Pernicious anaemia
The special features are:
- Due to intrinsic factor deficiency
- Gastric atrophy with histamine fast achlorhydria
- Genetic basis (racial distribution and blood group A).
- Seen with auto immune disorders.
- Antibodies to parietal cells and to intrinsic factors are seen
Systemic Candidiasis (Candidosis; Moniliasis)
Invasive infections caused by Candida sp, most often C. albicans, manifested by fungemia, endocarditis, meningitis, and/or focal lesions in liver, spleen, kidneys, bone, skin, and subcutaneous or other tissues.
Infections due to Candida sp account for about 80% of all major systemic fungal infections.
Symptoms and Signs
Esophagitis is most often manifested by dysphagia. Symptoms of respiratory tract infections are nonspecific, such as cough. Vaginal infections cause itching, burning, and discharge. Candidemia usually causes fever, but other symptoms are typically nonspecific. Sometimes, a syndrome develops resembling bacterial sepsis, with a fulminating course that may include shock, oliguria, renal shutdown, and disseminated intravascular coagulation.
Hematogenous endophthalmitis starts as white retinal plaques that can cause blindness as destructive inflammation progresses, extending to opacify the vitreous and causing potentially irreversible scarring. Most often, there are no symptoms in early stages of Candida endophthalmitis. If treatment is not begun before symptoms appear, significant or even total loss of vision is likely to occur in the affected eye. In neutropenic patients, eye involvement is more often manifested by retinal hemorrhages; papulonodular, erythematous, and vasculitic skin lesions may also develop.
Multiple sclerosis
a. A demyelinating disease that primarily affects myelin (i.e. white matter). This affects the conduction of electrical impulses along the axons of nerves. Areas of demyelination are known as plaques.
b. The most common demyelinating disease.
c. Onset of disease usually occurs between ages 20 and 50; slightly more common in women.
d. Disease can affect any neuron in the central nervous system, including the brainstem and spinal cord. The optic nerve (vision) is commonly affected.
Diseases from Str. pyogenes (Group A strep)
1. Streptococcal pharyngitis. Most frequent Group A infection. Throat has gray-white exudate. Infection may become systemic into blood, sinuses, jugular vein, meninges. In less than a week the M-protein and capsule production decrease, and transmission declines.
2. Skin infections, such as impetigo. Especially in children. Different M-proteins than in pharyngitis. Skin infections associated with edema and red streaking (characteristic).
3. Necrotizing fasciitis/myositis. Infection of deeper tissue advances despite antibiotics.
4. Scarlet fever. Caused by phage-associated erythrogenic toxin-producing strains. Toxins cause cardiac, renal, and other systemic failures. Rash is very red with a sand-papery feel and shedding of superficial skin.
5. Toxic Shock Syndrome. Parallels the toxic shock caused by TSST-carrying Staph. aureus.
6. Non-suppurative, post-infection diseases.
Rheumatic fever (myocarditis, cardiac valve disease, polyarthralgia, rashes. Occurs two weeks after a pharyngeal infection)
Glomerulonephritis (Occurs two weeks after pharyngeal or skin infections. Often due to immunologic reaction to M-protein type 12)
Thyroid goitres
A goitre is any enlargement of part or whole of the thyroid gland. There are two types:
1. Toxic goitre, i.e. goitre associated with thyrotoxicosis.
2. Non-toxic goitre, i.e. goitre associated with normal or reduced levels of thyroid hormones.
Toxic goitre
Graves disease
This is the most common cause of toxic goitre
Toxic multinodular goitre
This results from the development of hyperthyroidism in a multinodular goitre
Non-toxic goitres
Diffuse non-toxic goitre (simple goitre)
This diffuse enlargement of the thyroid gland is classified into:
Endemic goitre—due to iodine deficiency. Endemic goiter occurs in geographic areas (typically mountainous)) where the soil, water, and food supply contain little iodine. The term endemic is used when goiters are present in more than 10% of the population in a given region. With increasing availability of dietary iodine supplementation, the frequency and severity of endemic goiter have declined significantly. Sporadic goiter is less common than endemic goiter. The condition is more common in females than in males, with a peak incidence in puberty or young adult life, when there is an
increased physiologic demand for T4.
Sporadic goitre—caused by goitrogenic agents (substances that induce goitre formation) or familial in origin. Examples of goitrogenic agents include certain cabbage species, because of their thiourea content, and specific drugs or chemicals, such as iodide, paraminosalicylic acid and drugs used in the treatment of thyrotoxicosis. Familial cases show inherited autosomal recessive traits, which interfere with hormone synthesis via various enzyme pathways (these are dyshormonogenic goitres).
Hereditary enzymatic defects interfering with thyroid hormone synthesis (dyshormonogenetic goiter).
Physiological goitre—enlargement of the thyroid gland in females during puberty or pregnancy; the reason is unclear.
Multinodular goitre
This is the most common cause of thyroid enlargement and is seen particularly in the elderly (nearly all simple goitres eventually become multinodular). The exact aetiology is uncertain but it may represent an uneven responsiveness of various parts of the thyroid to fluctuating TSH levels over a period of many years.
Morphological features are:
• Irregular hyperplastic enlargement of the entire thyroid gland due to the development of wellcircumscribed nodules of varying size.
• Larger nodules filled with brown, gelatinous colloid; consequently, it is often termed multinodular colloid goitres.
Clinical features
- A large neck mass, goiters may also cause airway obstruction, dysphagia, and compression of large vessels in the neck and upper thorax.
- A hyperfunctioning ("toxic") nodule may develop within a long-standing goiter, resulting in hyperthyroidism. This condition is not accompanied by the infiltrative ophthalmopathy and dermopathy.
- Less commonly, there may be hypothyroidism.
ADRENOCORTICAL TUMORS
Functional adenomas are commonly associated with hyperaldosteronism and with Cushing syndrome, whereas a virilizing neoplasm is more likely to be a carcinoma. Determination of of the functional status of a tumor is based on clinical evaluation and measurement of the hormone or its metabolites. In other words, functional and nonfunctional adrenocortical neoplasms cannot be distinguished on the basis of morphologic features.
Patholgical features
Adrenocortical adenomas
- They are generally small, 1 to 2 cm in diameter.
- On cut surface, adenomas are usually yellow to yellow-brown due to presence of lipid within the neoplastic cells
- Microscopically, adenomas are composed of cells similar to those populating the normal adrenal cortex. The nuclei tend to be small, although some degree of pleomorphism may be encountered even in benign lesions ("endocrine atypia"). The cytoplasm ranges from eosinophilic to vacuolated, depending on their lipid content.
Adrenocortical carcinomas
These are rare and may occur at any age, including in childhood.
- Carcinomas are generally large, invasive lesions.
- The cut surface is typically variegated and poorly demarcated with areas of necrosis, hemorrhage, and cystic change.
- Microscopically, they are composed of well-differentiated cells resembling those of cortical adenomas or bizarre, pleomorphic cells, which may be difficult to distinguish from those of an undifferentiated carcinoma metastatic to the adrenal.