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.
Hyperparathyroidism
Abnormally high levels of parathyroid hormone (PTH) cause hypercalcemia. This can result from either primary or secondary causes. Primary hyperparathyroidism is caused usually by a parathyroid adenoma, which is associated with autonomous PTH secretion. Secondary hyperparathyroidism, on the other hand, can occur in the setting of chronic renal failure. In either situation, the presence of excessive amounts of this hormone leads to significant skeletal changes related to a persistently exuberant osteoclast activity that is associated with increased bone resorption and calcium mobilization. The entire skeleton is affected. PTH is directly responsible for the bone changes seen in primary hyperparathyroidism, but in secondary hyperparathyroidism additional influences also contribute. In chronic renal failure there is inadequate 1,25- (OH)2-D synthesis that ultimately affects gastrointestinal calcium absorption. The hyperphosphatemia of renal
failure also suppresses renal α1-hydroxylase, which further impair vitamin D synthesis; all these eventuate in hypocalcemia, which stimulates excessive secretion of PTH by the parathyroid glands, & hence elevation in PTH serum levels.
Gross features
• There is increased osteoclastic activity, with bone resorption. Cortical and trabecular bone are lost and replaced by loose connective tissue.
• Bone resorption is especially pronounced in the subperiosteal regions and produces characteristic radiographic changes, best seen along the radial aspect of the middle phalanges of the second and third fingers.
Microscopical features
• There is increased numbers of osteoclasts and accompanying erosion of bone surfaces.
• The marrow space contains increased amounts of loose fibrovascular tissue.
• Hemosiderin deposits are present, reflecting episodes of hemorrhage resulting from microfractures of the weakened bone.
• In some instances, collections of osteoclasts, reactive giant cells, and hemorrhagic debris form a distinct mass, termed "brown tumor of hyperparathyroidism". Cystic change is common in such lesions (hence the name osteitis fibrosa cystica). Patients with hyperparathyroidism have reduced bone mass, and hence are increasingly susceptible to fractures and bone deformities.
Primary vs. secondary disorders - Most nutritional disorders in developed countries are not due to simple dietary deficiencies but are rather a secondary manifestation of an underlying primary condition or disorder.
• Chronic alcoholism
• Pregnancy and lactation
• Renal dialysis
• Eating disorders
• Prolonged use of diuretics
• Malabsorption syndromes
• Neoplasms
• Food fads
• Vegans
• AIDS
STOMACH
Congenital malformations
1. Pyloric stenosis
Clinical features. Projectile vomiting 3-4 weeks after birth associated with a palpable "olive" mass in the epigastric region is observed.
Pathology shows hypertrophy of the muscularis of the pylorus and failure to relax.
2. Diaphragmatic hernias are due to weakness in or absence of parts of the diaphragm, allowing herniation of the abdominal contents into the thorax.
Inflammation
1. Acute gastritis (erosive)
Etiology. Alcohol, aspirin and other NSAIDs, smoking, shock, steroids, and uremia may all cause disruption of the mucosal barrier, leading to inflammation.
Clinical features. Patients experience heartburn, epigastric pain, nausea, vomiting, hematemesis, and even melena.
2. Chronic gastritis (nonerosive) may lead to atrophic mucosa with lymphocytic infiltration.
Types
(1) Fundal (Type A) gastritis is often autoimmune in origin. It is the type associated with pernicious anemia and, therefore, achlorhydria and intrinsic factor deficiency.
(2) Antral (Type B) gastritis is most commonly caused by Helicobacter pylori and is the most common form of chronic gastritis in the U.S. H. pylori is also responsible for proximal duodenitis in regions of gastric metaplasia.
Clinical features. The patient may be asymptomatic or suffer epigastric pain, nausea, vomiting, and bleeding. Gastritis may predispose to peptic ulcer disease, probably related to H. pylori infection.
3. Peptic ulcers
Peptic ulcers are usually chronic, isolated ulcers observed in areas bathed by pepsin and HCI; they are the result of mucosal breakdown
Common locations are the proximal duodenum, the stomach, and the esophagus, often in areas of Barrett's esophagus.
Etiology. There are several important etiologic factors.
Duodenal ulcers occur predominantly in patients with excess acid secretion, while gastric ulcers usually occur in patients with lower than average acid secretion.
Other predisposing conditions include smoking, cirrhosis, pancreatitis, hyperparathyroidism, and H. pylori infection. Aspirin, steroids, and NSAlDs are known to be assoicated with peptic ulcer disease. Next to H. pylori colonization, aspirin or NSAID ingestion is the most common cause of peptic ulcer.
Clinical features. Patients experience episodic epigastric pain. Duodenal and most gastric ulcers are relieved by food or antacids. Approximately one-fifth of gastric ulcer patients get no relief from eating or experience pain again within 30 minutes.
Pathology. Benign peptic ulcers are well-circumscribed lesions with a loss of the mucosa, underlying scarring, and sharp walls.
Complications include hemorrhage, perforation, obstruction, and pain. Duodenal ulcers do not become malignant .Gastric ulcers do so only rarely; those found to be ma1ignant likely originated as a cancer that ulcerated.
Diagnosis is made by upper gastrointestinal Series , endoscopy, and biopsy to rule out malignancy or to demonstrate the presence of H. pylori.
4. Stress ulcers
are superficial mucosal ulcers of the stomach or duodenum or both. Stress may be induced by burns, sepsis shock, trauma, or increased intracranial pressure.
Tumors
1. Benign
a. Leiomyoma, often multiple, is the most common benign neoplasm of the stomach. Clinical features include bleeding, pain, and iron deficiency anemia.
b. Gastric polyps are due to proliferation of the mucosal epithelium.
2. Malignant tumors
a. Carcinoma
Etiology. Primary factors include genetic predisposition and diet; other factors include hypochlorhydria, pernicious anemia, atrophic gastritis, adenomatous polyps, and exposure to nitrosamines. H. pylori are also implicated.
Clinical features. Stomach cancer is usually asymptomatic until late, then presents with anorexia, weight loss, anemia, epigastric pain, and melena. Virchow's node is a common site of metastasis.
Pathology. Symptomatic late gastric carcinoma may be expanding or infiltrative. In both cases the prognosis is poor (approximately 10% 5-year survival), and metastases are frequently present at the time of diagnosis.
Adenocarcinomas are most common.
b. Gastrointestinal lymphomas may be primary In the gastrointestinal tract as solitary masses.
c. Sarcoma is a rare, large, ulcerating mass that extends into the lumen.
d. Metastatic carcinoma. Krukenberg's tumor is an ovaria metastasis from a gastric carcinoma.
e. Kaposi's sarcoma. The stomach is the most commonly involved GI organ in Kaposi's sarcoma. It primarily occurs in homosexual men, appearing as hemorrhagic polypoid, umbilicated nodular lesions, typically in a submucosal location. It rarely causes symptoms
Achrondroplasia
is a major cause of dwarfism. The underlying etiology is a point mutation in the fibroblast growth factor receptor, which causes inhibition of chondrocyte proliferation, which is associated with suppression of the normal epiphyseal growth plate expansion. Thus, long bone growth is markedly shortened.
The most conspicuous changes include disproportionate shortening of the proximal extremities, bowing of the legs, and a lordotic posture.
Microscopically, the cartilage growth plates are disorganized and hypoplastic.
Glomerulonephritis
Characterized by inflammation of the glomerulus.
Clinical manifestations:
Nephrotic syndrome (nephrosis) → Most often caused by glomerulonephritis.
Laboratory findings:
(i) Proteinuria (albuminuria) and lipiduria—proteins and lipids are present in urine.
(ii) Hypoalbuminemia—decreased serum albumin due to albuminuria.
(iii) Hyperlipidemia—especially an increase in plasma levels of low-density lipoproteins and cholesterol.
Symptoms
severe edema, resulting from a decrease in colloid osmotic pressure due to a decrease in serum albumin.
Respiratory Viral Diseases
Respiratory viral infections cause acute local and systemic illnesses. The common cold, influenza, pharyngitis, laryngitis (including croup), and tracheobronchitis are common.
An acute, usually afebrile, viral infection of the respiratory tract, with inflammation in any or all airways, including the nose, paranasal sinuses, throat, larynx, and sometimes the trachea and bronchi.
Etiology and Epidemiology
Picornaviruses, especially rhinoviruses and certain echoviruses and coxsackieviruses, cause the common cold. About 30 to 50% of all colds are caused by one of the > 100 serotypes of rhinoviruses.
Symptoms and Signs
Clinical symptoms and signs are nonspecific.
After an incubation period of 24 to 72 h, onset is abrupt, with a burning sensation in the nose or throat, followed by sneezing, rhinorrhea, and malaise.
Characteristically, fever is not present, particularly with a rhinovirus or coronavirus. Pharyngitis usually develops early; laryngitis and tracheobronchitis vary by person and causative agent. Nasal secretions are watery and profuse during the first days, but become more mucoid and purulent.
Cough is usually mild but often lasts into the 2nd wk.