NEET MDS Lessons
General Pathology
THYROIDITIS
The more common and clinically significant thyroidites are:
1. Hashimoto thyroiditis
2. Subacute granulomatous thyroiditis
3. Subacute lymphocytic thyroiditis
Hashimoto thyroiditis
Hashimoto thyroiditis (Chronic Lymphocytic Thyroiditis) is the most common cause of hypothyroidism. It results from gradual autoimmune destruction of the thyroid gland. There is striking female predominance (10: 1 to 20:1), and is most prevalent around a mean age of 50 years.
Pathogenesis
• The dominant feature is progressive destruction of thyroid follicular epithelial cells with gradual replacement by mononuclear cell infiltration and fibrosis.
• Sensitization of CD4+ T-helper cells to thyroid antigens seems to be the initiating event.
• The reaction of CD4+ T cells with thyroid antigens produces interferon γ which promote inflammation and activate macrophages. Injury to the thyroid results from the toxic products of these inflammatory cells.
• CD8+ cytotoxic T cells also contribute to epithelial cells killing as are natural killer cells.
• There is a significant genetic component to disease pathogenesis. This is supported by
1. The increased frequency of the disease in first-degree relatives,
2. Unaffected family members often have circulating thyroid autoantibodies.
Gross features
• The thyroid shows moderate, diffuse, and symmetric enlargement.
• The cut surface is pale, gray-tan, firm, nodular and somewhat friable.
• Eventually there is thyroid atrophy
Microscopic features
• There is widespread, diffuse infiltration of the parenchyma by small lymphocytes, plasma cells. The lymphocytes are also form follicles some with well-developed germinal centers
• The thyroid follicles are atrophic and lined by epithelial cells having abundant eosinophilic, granular cytoplasm (Hurthle cells). This is a metaplastic response to the ongoing injury; ultrastructurally the Hurthle cells are stuffed by numerous mitochondria.
• Interstitial connective tissue is increased and may be abundant.
Hashimoto thyroiditis presents as painless symmetrical goiter, usually with some degree of hypothyroidism. In some cases there is an initial transient thyrotoxicosis caused by disruption of thyroid follicles, with secondary release of thyroid hormones ("hashitoxicosis"). As hypothyroidism supervenes T4 and T3 levels progressively fall & TSH levels are increased. Patients often have other autoimmune diseases and are at increased risk for the development of B-cell non-Hodgkin lymphomas.
Subacute Granulomatous (de Quervain) Thyroiditis
Subacute Granulomatous (de Quervain) Thyroiditis is much less common than Hashimoto disease.
- It is most common around the age of 40 years and occurs more frequently in women than in men.
- An upper respiratory infection just before the onset of thyroiditis. Thus, a viral infection is probably the cause.
- There is firm uni- or bilateral enlargement of the gland.
Microscopically, there is disruption of thyroid follicles, with extravasation of colloid. The extravasated colloid provokes a granulomatous reaction, with giant cells.
Thyroid function tests are those of thyrotoxicosis but with progression and gland destruction, a transient hypothyroid phase occurs. The condition is self-limited, with most patients returning to a euthyroid state within at most 2 months.
Subacute Lymphocytic Thyroiditis
Subacute Lymphocytic Thyroiditis may follow pregnancy (postpartum thyroiditis).
- It is most likely autoimmune in etiology, because circulating antithyroid antibodies are found in the majority of patients.
- It mostly affects middle-aged women and present as painless, mild, symmetric neck mass. Initially, there is thyrotoxicosis, followed by return to a euthyroid state within a few months. In a minority there is progression to hypothyroidism.
Microscopically, there is a lymphocytic infiltration and hyperplastic germinal center within the thyroid parenchyma; unlike Hashimoto thyroiditis, follicular atrophy or Hürthle cell metaplasia are not commonly seen.
Riedel thyroiditis
Riedel thyroiditis is a rare disorder of unknown etiology, characterized by extensive fibrosis involving the thyroid and the surrounding neck structures. The presence of a hard and fixed thyroid mass may be confused clinically with thyroid cancer. It may be associated with idiopathic fibrosis in other sites, such as the retroperitoneum. The presence of circulating antithyroid antibodies in most patients suggests an autoimmune etiology.
Malnutrition
A. Marasmus - calorie malnutrition
A child with marasmus suffers growth retardation and loss of muscle. The loss of muscle mass results from catabolism and depletion of the somatic protein compartment.
With such losses of muscle and subcutaneous fat, the extremities are emaciated; by comparison, the head appears too large for the body. Anemia and manifestations of multivitamin deficiencies are present, and there is evidence of immune deficiency, particularly of T cell-mediated immunity.
B. Kwashiorkor - protein malnutrition - importance of protein quality as well as quantity
Marked protein deprivation is associated with severe loss of the visceral protein compartment, and the resultant hypoalbuminemia gives rise to generalized, or dependent, edema.
The weight of children with severe kwashiorkor is typically 60% to 80% of normal.
However, the true loss of weight is masked by the increased fluid retention (edema).
Children with kwashiorkor have characteristic skin lesions, with alternating zones of hyperpigmentation, areas of desquamation, and hypopigmentation, giving a "flaky paint" appearance.
Hair changes include overall loss of color or alternating bands of pale and darker hair, straightening, line texture, and loss of firm attachment to the scalp.
An enlarged, fatty liver (resulting from reduced synthesis of carrier proteins) and a tendency to develop early apathy, listlessness, and loss of appetite.
The bone marrow in both kwashiorkor and marasmus may be hypoplastic, mainly because of decreased numbers of red cell precursors. How much of this derangement is due to a deficiency of protein and folates or to reduced synthesis of transferrin and ceruloplasmin is uncertain. Thus, anemia is usually present, most often hypochromic microcytic anemia, but a concurrent deficiency of folates may lead to a mixed microcytic-macrocytic anemia.
C. Most cases of severe malnutrition are a combination of A and B usually characterized by:
• Failure of growth
• Behavioral changes
• Edema (kwashiorkor)
• Dermatosis
• Changes in hair
• Loss of appetite
• Liver enlargement
• Anemia
• Osteoporosis
Hematological examination
This is a method by which abnormalities of the cells of the blood and their precursors in the bone marrow are investigated to diagnose the different kinds of anemia & leukemia.
Verruca vulgaris
1. Commonly known as warts.
2. Caused by the human papillomavirus (HPV).
3. Warts can be seen on skin or as an oral lesion (vermilion border, oral mucosa, or tongue).
4. Transmitted by contact or autoinoculation.
5. A benign lesion.
Acute tubular necrosis
Characterized by impaired kidney functions due to the destruction of the renal tubule epithelium.
Caused by a variety of conditions that lead to ischemia of the renal tubules, usually resulting from renal tubular injury or problems with vascular flow. It can also be induced by ingesting toxins or drug-related toxicity (e.g., gentamicin).
The most common cause of acute renal failure.
Is a reversible condition, although it can be fatal.
Thalassaemia. Genetic based defect in synthesis of one of the normal chains.
Beta thalassaemia ---> reduced Hb A and increased HbF (α2, Y2) HBA2(α2)
Alpha thalassaemia ---> reduced Hb-A, Hb-A2 and Hb-F-with formation of Hb-H(β4) and Hb Barts (Y4).
Thalassaemia may manifest as trait or disease or with intermediate manifestation.
Features:
• Microcytic hypochromic RBC is in iron deficjency.
• Marked anisopoikilocytsis with prominent target cells.
• Reticulocytosis and nucleated RBC seen.
• Mongoloid facies and X-ray findings characteristic of marrow hyperplasia
• Decreased osmotic. fragility.
• Increased marrow iron (important difference from iron deficiency anaemia).
• Haemosiderosis, especially with repeated transfusions.
Diagnosis is by Hb electrophoresis and by Alkali denaturation test (for HbF).
Vitiligo is an autoimmune destruction of melanocytes resulting in areas of depigmentation.
- commonly associated with other autoimmune diseases such as pernicious anemia, Addison's disease, and thyroid disease.
- common in the Black population