NEET MDS Lessons
General Pathology
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.
Cardiac tamponade
A. Caused by accumulation of fluid in the pericardium. This severe condition can quickly impair ventricular filling and rapidly lead to decreased cardiac output and death.
1. Signs and symptoms include:
a. Hypotension.
b. Jugular venous distention.
c. Distant heart sounds.
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.
Human immunodeficiency virus (HIV)
1. Part of the Retroviridae family (i.e., it is a retrovirus).
2. Basic virion structure
a. The nucleocapsid contains single stranded RNA and three enzymes: reverse transcriptase, integrase, and protease.
b. An exterior consists of two glycoproteins, gp120 and gp41, which are imbedded in the lipid bilayer. This lipid bilayer was obtained from the host cell via budding.
3. Virion characteristics
a. The HIV genome includes:
(1) gag gene—codes for core proteins.
(2) pol gene—codes for its three enzymes.
(3) env gene—codes for its two envelope glycoproteins.
b. HIV enzymes
(1) Reverse transcriptase—reverse transcription of RNA to viral DNA.
(2) Integrase—responsible for integrating viral DNA into host DNA.
(3) Protease—responsible for cleaving precursor proteins.
4. Pathogenicity
a. HIV mainly infects CD4 lymphocytes, or helper T cells. Its envelope protein, gp120, binds specifically with CD4 surface
receptors. After entry, viral RNA is transcribed by reverse transcriptase to viral DNA and integrated into the host DNA. New virions are synthesized and released by lysis of the host cell.
b. The predominant site of HIV replication is lymphoid tissues.
c. Although HIV mainly infects CD4 helper T cells, it can bind to any cell with a CD4 receptor, including macrophages, monocytes, lymph node dendritic cells, and a selected number of nerve cells. Macrophages are the first cells infected by HIV.
5. HIV infection versus acquired immunodeficiency syndrome (AIDS).
a. AIDS describes an HIV-infected person who has one of the following conditions:
(1) A CD4 lymphocyte count of less than 200.
(2) The person is infected with an opportunistic infection or other AIDS-defining illness, including (but not limited to) tuberculosis, recurrent pneumonia infections, or invasive cervical cancer.
b. The cause of death in an AIDS patient is most likely due to an opportunistic infection.
6. Common opportunistic infections associated with AIDS:
a. Pneumonia caused by Pneumocystis jiroveci (carinii).
b. Tuberculosis.
c. Periodontal disease—severe gingivitis, periodontitis, ANUG, necrotizing stomatitis.
d. Candidiasis.
e. Oral hairy leukoplakia (EBV).
f. Kaposi’s sarcoma (HHV-8).
g. Recurrent VZV infections.
h. Condyloma acuminatum or verruca vulgaris (warts, HPV)—less common.
i. CMV infections.
j. Disseminated herpes simplex, herpes zoster.
k. Hodgkin’s, non-Hodgkin’s lymphoma.
7. Laboratory diagnosis of HIV
a. ELISA test—detects HIV antibodies.
False negatives do occur.
b. Western blot—detects HIV proteins.
There is a 99% accuracy rate when both the ELISA test and Western blot are used to diagnose HIV infection.
c. PCR—more sensitive; can amplify and identify the virus at an early stage.
8. Treatment
a. Inhibitors of reverse transcriptase.
(1) Nucleoside analogs
(a) Inhibit viral replication via competitive inhibition.
(b) Examples: zidovudine (AZT), didanosine, lami- vudine, stavudine.
(2) Nonnucleoside inhibitors.
(a) Act by binding directly to reverse transcriptase.
(b) Examples: nevirapine, delavirdine.
b. Protease inhibitor.
c. “Triple cocktail” therapy—often consists of two nucleoside inhibitors and a protease inhibitor.
Salivary gland pathology
Inflammation
a. Sialolithiasis produces a secondary inflammatory reaction to obstruction and the resultant enlargement of ducts by stones. It may be complicated by actual infection with mouth flora.
b. Sialadenitis is a primary inflammatory reaction, but it is not always infectious. It may be part of an autoimmune disease (e.g., Sjogren's syndrome), or the result of bacterial or virals (e.g., mumps) infection.
Sjögren’s syndrome
a. An autoimmune disease of the salivary and lacrimal glands.
b. Autonuclear antibodies (ANAs) against salivary ducts may be seen.
c. Triad of symptoms include:
(1) Xerostomia—from decreased saliva production.
(2) Keratoconjunctivitis sicca (dry eyes)—from decreased tear production.
(3) Rheumatoid arthritis.
(4) Enlargement of the salivary or lacrimal glands, known as Mikulicz syndrome, may also be observed.
d. Histologically, a dense infiltration of the gland by lymphocytes is observed.
Tumors
The parotid gland accounts for more than three-quarters of these tumors, most of which are benign. Of the remainder, more occur in the submandibular gland than in the sublingual, and most of these are malignant. Many are surgically, cured, but local recurrence is common.
a. Pleomorphic adenoma is generally benign and accounts for approximately three-quarters of all salivary gland tumors. If is composed of multiple epithelial and mesenchymal cell types. Complications may arise due to involvement of cranial nerve VII.
(a) The most common salivary gland tumor.
(b) Is benign.
(c) Prognosis is good after proper surgical excision.
b. Warthin's tumor (adenolymphoma) is also benign, occuring almost exclusively in the parotid gland. It is grossly cystic.
Microscopic examination reveals cell types suggestive of branchial cleft origin embedded in a lymphoid matrix.
c. Mucoepidermoid tumors also occur primarily in the parotid and have a high rate of malignant transformation.The malignant component is usually squamous cell. Prognosis of tumor depends on grade and stage of disease.
d. Cylindroma (adenoid cysticc. Mucoepidermoid tumors carcinoma) is more common in the minor salivary glands found in the oral mucosa, and metastases are more common than in other tumors of the salivary glands. Facial nerve complications are frequent.
(1) Grossly, the tumor forms multiple lobules surrounded by a capsule.
(2) Microscopically, small cells form glands containin mucoid material
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.
Pulmonary embolism
A pulmonary embolism (thromboembolism) occurs when a blood clot, generally a venous thrombus, becomes dislodged from its site of formation and embolizes to the arterial blood supply of one of the lungs.
Clinical presentation
Signs of PE are sudden-onset dyspnea (shortness of breath, 73%), tachypnea (rapid breathing, 70%), chest pain of "pleuritic" nature (worsened by breathing, 66%), cough (37%), hemoptysis (coughing up blood, 13%), and in severe cases, cyanosis, tachycardia (rapid heart rate), hypotension, shock, loss of consciousness, and death. Although most cases have no clinical evidence of deep venous thrombosis in the legs, findings that indicate this may aid in the diagnosis.
Diagnosis
The gold standard for diagnosing pulmonary embolism (PE) is pulmonary angiography
An electrocardiogram may show signs of right heart strain or acute cor pulmonale in cases of large PEs
In massive PE, dysfunction of the right side of the heart can be seen on echocardiography, an indication that the pulmonary artery is severely obstructed and the heart is unable to match the pressure.
Treatment
Acutely, supportive treatments, such as oxygen or analgesia
In most cases, anticoagulant therapy is the mainstay of treatment. Heparin or low molecular weight heparins are administered initially, while warfarin therapy is given