NEET MDS Lessons
General Pathology
Sickle Cell Disease
Sickle cell anemia is a autosomal recessive genetic disorder. It affects the BETA GLOBIN gene on the CHROMOSOME 16. In sickle cell anemia, the hemoglobin abnormality consists of a point mutation in the beta chain gene for hemoglobin; the resulting abnormal gene product is denoted HbS. If you are heterozygous for the HbS gene you will have what is called sickle trait, which is asymptomatic .
If you are homozygous for the HbS gene you will get sickle cell disease, which is symptomatic in most patients.
The problem with HbS is that as it releases oxygen, it polymerizes and aggregates with other HbS molecules, making the red cell stiff and distorted. These distorted, sickle-shaped red cells are fragile so the patient can end up with a hemolytic anemia.
This can occur as pure disease (homozygous) or trait (heterozygous) or with other haemoglobinopathies. It is common. in Negroes. It is due to Hb-s which is much less soluble than Hb-A hence deoxygenation insoluble form sickling of RBC.
This causes:
• Removal by RE system.
• Blockage of microvessels causing ischaemia.
Ichthyosis vulgaris is a genetic disease characterized by increased cohesiveness of the cells in the stratum corneum, resulting up in a piling up stratum corneum (scales like a fish).
Viral meningitis
1. Can be caused by many different viruses, including cytomegalovirus, herpes virus, rabies, and HIV.
2. CSF fluid from a spinal tap differs from that seen in a bacterial infection. It shows mononuclear cells, higher levels of protein, and normal levels of glucose.
Other lung diseases
1.Sarcoidosis
1. Sarcoidosis
a. More common in African-Americans.
b. Associated with the presence of noncaseating granulomas.
Sarcoidosis is an immune system disorder characterised by non-necrotising granulomas (small inflammatory nodules). Virtually any organ can be affected, however, granulomas most often appear in the lungs or the lymph nodes.
Signs and symptoms
- Sarcoidosis is a systemic disease that can affect any organ. Common symptoms are vague, such as fatigue unchanged by sleep, lack of energy, aches and pains, dry eyes, blurry vision, shortness of breath, a dry hacking cough or skin lesions. The cutaneous symptoms are protean, and range from rashes and noduli (small bumps) to erythema nodosum or lupus pernio
- Renal, liver, heart or brain involvement may cause further symptoms and altered functioning. Manifestations in the eye include uveitis and retinal inflammation
- Sarcoidosis affecting the brain or nerves is known as neurosarcoidosis.
- Hypercalcemia (high calcium levels) and its symptoms may be the result of excessive vitamin D production
- Sarcoidosis most often manifests as a restrictive disease of the lungs, causing a decrease in lung volume and decreased compliance (the ability to stretch). The vital capacity (full breath in, to full breath out) is decreased, and most of this air can be blown out in the first second. This means the FEV1/FVC ratio is increased from the normal of about 80%, to 90%.
Treatment
Corticosteroids, most commonly prednisone
2. Cystic fibrosis
a. Transmission: caused by a genetic mutation (nucleotide deletion) on chromosome 7, resulting in abnormal chloride channels.
b. The most common hereditary disease in Caucasians.
c. Genetic transmission: autosomal recessive.
d. Affects all exocrine glands. Organs affected include lungs, pancreas, salivary glands, and intestines. Thick secretions or mucous plugs are
seen to obstruct the pulmonary airways and intestinal tracts.
e. Is ultimately fatal.
f. Diagnostic test: sweat test—sweat contains increased amounts of chloride.
3. Atelectasis
a. Characterized by collapse of the alveoli.
b. May be caused by a deficiency of surfactant and/or hypoventilation of alveoli.
Pathology gives explanations of a disease by studying the following four aspects of the disease.
1. Etiology,
2. Pathogenesis,
3. Morphologic changes and
4. Functional derangements and clinical significance.
1. Etiology Etiology of a disease means the cause of the disease. If the cause of a disease is known it is called primary etiology. If the cause of the disease is unknown it is called idiopathic. Knowledge or discovery of the primary cause remains the backbone on which a diagnosis can be made, a disease understood, & a treatment developed. There are two major classes of etiologic factors: genetic and acquired (infectious, nutritional, chemical, physical, etc).
2. Pathogenesis Pathogenesis means the mechanism through which the cause operates to produce the pathological and clinical manifestations. The pathogenetic mechanisms could take place in the latent or incubation period. Pathogenesis leads to morphologic changes.
3. Morphologic changes The morphologic changes refer to the structural alterations in cells or tissues that occur following the pathogenetic mechanisms. The structural changes in the organ can be seen with the naked eye or they may only be seen under the microscope. Those changes that can be seen with the naked eye are called gross morphologic changes & those that are seen under the microscope are called microscopic changes. the morphologic changes will lead to functional alteration & to the clinical signs & symptoms of the disease.
4. Functional derangements and clinical significance The morphologic changes in the organ influence the normal function of the organ. By doing so, they determine the clinical features (symptoms and signs), course, and prognosis of the disease.
EXOCRINE PANCREAS
Congenital anomalies
1. Ectopic pancreatic tissue most commonly occurs in the stomach, duodenum, jejunum, Meckel's diverticulum, and ileum. It may be either asymptomatic or cause obstruction, bleeding, intussusception.
2.Annular pancreas is a ring of pancreatic tissue that encircle the duodenum and may cause duodenal obstruction.
Cystic fibrosis
Cystic fibrosis is a systemic disorder of exocrine gland secretion presenting during infancy or childhood.
Incidence is 1:2500 in Caucasians; it is less common in Black and extremely rare in Asians.
Pathogenesis. Cystic fibrosis shows autosomal recessive transmission; heterozygotes are unaffected. It results in a defective chloride channel, which leads to secretion of very thick mucus.
Characteristics
- Tissues other than exocrine glands are normal, and glands are structurally normal until damaged by cystic fibrosis.
- The only characteristic biochemical abnormalities are an elevation of sodium and chloride levels in sweat, and a decrease in water and bicarbonate secretion from pancreatic cells, resulting in a viscous secretion.
Clinical features
- Fifteen percent of cases present with meconium ileus.
- Most cases present during the first year with steatorrhea (with resultant deficiencies of vitamins A, D, E, and K), abdominal distention, and failure to thrive.
Complications are also related to pulmonary infections'and obstructive pulmonary disease as a result of viscous bronchial secretions.
Pathology
- There is mucus plugging of the pancreatic ducts with cystic dilatation, fibrous proliferation, and atrophy. Similar pathology develops in salivary glands.
- Lungs. Mucus impaction leads to bronchiolar dilatation an secondary infection.
- The gastrointestinal tract shows obstruction caused mucus impaction in the intestines with areas of biliary cirrhosis, resulting from intrahepatic bile duct obstruction
Diagnosis depends on demonstrating a "sweat test" abnomality associated with at least one clinical feature In sweat test, high levels of chloride are demonstrated.
Prognosis. Mean survival is age 20; mortality is most often due to pulmonary infections.
Degenerative changes
1. Iron pigmentation (e.g., from hemochromatosis) may be deposited within acinar and islet cells and may cause insulin deficiency.
2. Atrophy
a. Ischemic atrophy is due to atherosclerosis of pancreatic arteries and is usually asymptomatic.
b. Obstruction of pancreatic ducts affects only the exocrine pancreas, which becomes small, fibrous, and nodular.
Acute hemorrhagic pancreatitis
presents as a diffuse necrosis of the pancreas caused by the release of activated pancreatic
enzymes. Associated findings include fat necrosis and hemorrhage into the pancreas.
Incidence. This disorder is most often associated with alcoholism and biliary tract disease.
It affects middle-aged individuals and often occurs after a large meal or excessive alcohol ingestion; approximately 50% of patients have gallstones.
Pathogenesis. There are four theories.
- Obstruction of the pancreatic duct causes an elevated intraductal pressure, which results in leakage of enzymes from small ducts.
- obstruction may be caused by a gallstone at the ampulla of Vater; chronic alcohol ingestion may cause duct obstruction by edema.
- Hypercalcemia may cause activation of trypsinogen; its mechanism is unclear. Pancreatitis occurs in 20% of patients with hyperparathyroidism.
- Direct damage to acinar cells may occur by trauma, ischemia, viruses, and drugs.
- Hyperlipidemia may occur as a result of exogenous estrogen intake and alcohol ingestion.
Clinical features are typically the sudden onset of acute, continuous, and intense abdominal pain, often radiating to the back and accompanied by nausea, vomiting, and fever. This syndrome frequently results in shock.
Laboratory values reveal elevated amylase (lipase elevated after 3-4 days) and leukocytosis. Hypocalcemia is a poor prognostic sign.
Chronic pancreatitis
It refers to remitting and relapsing episodes of mild pancreatitis, causing progressive pancreatic damage.
Incidence is similar to acute pancreatitis. It is also seen in patients with ductal anomalies. Almost half the cases occur without known risk factors.
Pathogenesis is unclear; possibly, there is excess protein secretion by the pancreas, causing ductal obstruction.
Clinical features include flareups precipitated by alcohol and overeating, and drugs. Attacks are characterized by upper abdominal pain, tenderness, fever, and jaundice.
Laboratory values reveal elevated amylase and alkaline phosphatase, X-rays reveal calcifications in the pancreas. Chronic pancreatitis may result in pseudocyst formation, diabetes, and steatorrhea.
Carcinoma of the pancreas
Incidence:
Carcinoma of the pancreas accounts for approximately 5% of all cancer deaths. Increased risk is associated with smoking. high-fat diet, and chemical exposure. There is a higher incidence in the elderly, Blacks, males, and diabetics.
Clinical features
- The disease is usually asymptomatic until late in its course.
- Manifestations include weight loss, abdominal pain frequently radiating to the back, weakness, malaise, anorexia, depression, and ascites.
- There is jaundice in half of the patients who have carcinoma of the head of the pancreas.
- Courvoisier's law holds that painless jaundice with a palpable gallbladder is suggestive of pancreatic cancer.
Pathology
Carcinomas arise in ductal epithelium. Most are adenocarcinomas.
- Carcinoma of the head of the pancreas accounts for 60% of all pancreatic cancers.
- Carcinoma of the body (20%) and tail (5%) produce large indurated masses that spread widely to the liver and lymph nodes.
- In 15% of patients, carcinoma involves the pancreas diffusely.
Complications
include Trousseau's syndrome, a migratory thrombophlebitis that occurs in 10% of patients.
Prognosis is very poor. if resectable, the 5-year survival rate less than 5%. The usual course is rapid decline; on average death occurs 6 months after the onset of symptoms.
Neutrophilia
Causes
-Pyogenic infections.
-Haemorrhage and trauma.
-Malignancies.
-Infarction.
-Myelo proliferative disorders.