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.
Hepatitis D virus—can only infect cells previously infected with hepatitis B.
Delta hepatitis (HDV) is associated with a 35-nm RNA virus composed of a delta antigen-bearing core surrounded by HBV's Ag coat;
HDV requires HBV for replication.
Delta hepatitis can cause quiescent HBV states to suddenly worsened . Its transmission is the same as that of HBV.
Hepatitis E virus—a high mortality rate in infected pregnant women.
Hepatitis E (HEV) is caused by a single-stranded RNA virus. The disease is typically self-limited and does not evolve into chronic hepatitis; it may, however, be cholestatic.
Pregnant women may develop fulminant disease.
Transmission is by the fecal oral route.
HEV occurs mainly in India, Nepal, Pakistan, and Southeast Asia.
Tuberculosis
Causative organism
-Mycobacterium tuberculosis
-Strict aerobe
-Pathogenic strains
-hominis, bovis, avium, murine& cold blooded vertebrate strain
Koch’s bacillus
-small slender, rod like bacillus, 4umnon-motile, aerobic -high lipid content
-divides every 16 to 20 hours, an extremely slow rate
-stains very weakly Gram-positive or does not retain dye due to the high lipid & mycolicacid content of its cell wall
-can withstand weak disinfectant and survive in a dry state for weeks.
Demonstrated by
-ZiehlNeelsenstaining
-Fluorescent dye method
-Culture in LJ media
-Guinea pig inoculation
Modes of transmission
Inhalation , Ingestion, Inoculation , Transplacental
Route Spread
Local , Lymphatic , Haematogenous , By natural passages,
Pathogenesis
- Anti‐mycobacterial CMI, confers resistance to bacteria → dev. of HS to tubercular Ag
- Bacilli enters macrophages
- Replicates in phagosomeby blocking fusion of phagosome& lysosome, continues for 3 weeks →bacteremiabut asymptomatic
- After 3 wks, T helper response is mounted by IL‐12 produced by macrophages
- T cells produce IFN, activates macrophages → bactericidal activity, structural changes
- Macrophages secrete TNF→ macrophage recruitment, granuloma& necrosis
Fate of granuloma
- Caseousmaterial undergo liquefaction---cold abscess
- Bones, joints, lymph nodes & epididymis---sinuses are formed & sinus tract lined by tuberculousgranulation tissue
- Dystrophic calcification
Types of TB
1. Primary Pulmonary TB
2. secondary TB (miliary, fibrocaseous, cavitary)
3. Extra-pulmonary TB (bone, joints, renal, adrenal, skin… )
Primary TB
Infection in an individual who has not been previously infected or immunised
Primary complex
Sites
-lungs, hilarlymph nodes
-tonsils, cervical lymph nodes
-small intestine, mesenteric lymph nodes
Primary TB
In the lung, Ghon’scomplex has 3 components:
1. Pulmonary component -Inhalation of airborne droplet ~ 3 microns.
-Bacilli locate in the subpleuralmid zone of lung
-Brief acute inflammation –neutrophils.
-5-6 days-invoke granulomaformation.
-2 to 8 weeks –healing –single round ;1-1.5 cm-Ghon focus.
2. Lymphatic vessel component
3. Lymph node component
Fate of primary tuberculosis
- Lesions heal by fibrosis, may undergo calcification, ossification
-a few viable bacilli may remain in these areas
-bacteria goes into a dormant state, as long as the person's immune system remains active
- Progressive primary tuberculosis: primary focus continues to grow & caseousmaterial disseminated to other parts of lung
- Primary miliarytuberculosis: bacilli may enter circulation through erosion of blood vessel
- Progressive secondary tuberculosis: healed lesions are reactivated, in children & in lower resistance
Secondary tuberculosis
-Post-primary/ reinfection/ chronic TB
-Occurs in immunized individuals.
-Infection acquired from
-endogenous source/ reactivation
-exogenous source/ reinfection
Reactivation
-when immune system is depressed
-Common in low prevalence areas.
-Occurs in 10-15% of patients
-Slowly progressive (several months)
Re-infection
-when large innoculum of bacteria occurs
-In areas with increased personal contact
Secondary TB
-Sites-Lungs 1-2 cm apical consolidation with caseation
-Other sites -tonsils, pharynx, larynx, small intestine & skin
Fate of secondary tuberculosis
•Heal with fibrous scarring & calcification
•Progressive secondary pulmonary tuberculosis:
-fibrocaseoustuberculosis
-tuberculouscaseouspneumonia
-miliarytuberculosis
Complications:
a) aneurysm of arteries–hemoptysis
b) bronchopleuralfistula
c) tuberculousempyema
MiliaryTB
• Millet like, yellowish, firm areas without caseation
• Extensive spread through lympho-hematogenousroute
• Low immunity
• Pulmonary involvement via pulmonary artery
• Systemic through pulmonary vein:
-LN: scrofula, most common
-kidney, spleen, adrenal, brain, bone marrow
Signs and Symptoms of Active TB
• Pulmonary-cough, hemoptysis, dyspnea
• Systemic:
• fever
• night sweats
• loss of appetite
• weight loss
• chest pain,fatigue
•If symptoms persist for at least 2 weeks, evaluate for possible TB infection
Diagnosis
•Sputum-Ziehl Neelsen stain –10,000 bacilli, 60% sensitivity
-release of acid-fast bacilli from cavities intermittent.
-3 negative smears : low infectivity
•Culture most sensitive and specific test.
-Conventional Lowenstein Jensen media-10 wks.
-Liquid culture: 2 weeks
•Automated techniques within days
should only be performed by experienced laboratories (10 bacilli)
•PPD for clinical activity / exposure sometime in life
•X-ray chest
•FNAC
PPD Tuberculin Testing
- Read after 72 hours.
- Indurationsize -5-10 mm
- Does not d/s b/w active and latent infection
- False +: atypical mycobacterium
- False -: malnutrition, HD, viral, overwhelming infection, immunosuppression
- BCG gives + result.
Tuberculosis Atypical mycobacteria
- Photochromogens---M.kansasii
- Scotochromogens---M.scrofulaceum
- Non-chromogens---M.avium-intracellulare
- Rapid growers---M.fortuitum, M.chelonei
5 patterns of disease
- Pulmonary—M.kansasii, M.avium-intracellulare
- Lymphadenitis----M.avium-intracellulare, M.scrofulaceum
- Ulcerated skin lesions----M.ulcerans, M.marinum
- Abscess----M.fortuitum, M.chelonei
- Bacteraemias----M.avium-intracellulare as in AIDS
Malignant Diseases of Skin
1. Bowen's disease refers to a carcinoma in situ on sun-exposed skin or on the vulva, glans a penis, or oral mucosa which has an association, in some cases, with a visceral malignancy.
2. Skin cancers associated with ultraviolet light damage include basal cell carcinoma, squamous cell carcinoma, and malignant melanoma.
3. A basal cell carcinoma is the MC malignant tumor of the skin and occurs on sunexposed, hair-bearing surfaces.
- Locally aggressive, infiltrating cancers arising from the basal cell layer of the epidermis and infiltrate the underlying superficial dermis.
- they do not metastasize
- BCC are commonly located on the face on the inner aspect of the nose, around the orbit and the upper lip where they appear as raised nodules containing a central crater with a pearly-colored skin surface and vascular channels.
- microscopically, they have cords of basophilic staining cells originating from the basal cell layer infiltrating the dermis.
- they commonly recur if they are not totally excised, because they are frequently multifocal.
- the basal cell nevus syndrome is an autosomal-dominant disorder characterized by the development of basal cell carcinomas early in life with associated abnormalities of bone, skin, nervous system, eyes, and reproductive system.
Streptococcal pharyngitis:
A disease of young people, enlarged lymphoid nodules and keratin plugs in the tonsillar pits is seen Complications include retro-pharyngeal abscess (quinsy)
Cellulitis of the deep tissues of the neck is Ludwig's angina
Scarlet fever ("scarlatina") is a strep throat caused by a streptococcus with the gene to make one of the erythrogenic toxins, Patients have a rash with PMNs
Streptococcal skin infections (Impetigo)
Erysipelas is a severe skin infection caused by group A strep; geographic of red, thickened, indurated areas of the skin are characteristic. Unlike staph infections, there is usually little or no tissue necrosis
Post-streptococcal hypersensitivity diseases include rheumatic fever, post-streptococcal glomerulonephritis, and some cases of erythema nodosum
Rocky Mountain Spotted Fever (Spotted Fever; Tick Fever; Tick Typhus)
An acute febrile disease caused by Rickettsia rickettsii and transmitted by ixodid ticks, producing high fever, cough, and rash.
Symptoms and Signs
The incubation period averages 7 days but varies from 3 to 12 days; the shorter the incubation period, the more severe the infection. Onset is abrupt, with severe headache, chills, prostration, and muscular pains. Fever reaches 39.5 or 40° C (103 or 104° F) within several days and remains high (for 15 to 20 days in severe cases),
Between the 1st and 6th day of fever, most patients develop a rash on the wrists, ankles, palms, soles, and forearms that rapidly extends to the neck, face, axilla, buttocks, and trunk. Often, a warm water or alcohol compress brings out the rash. Initially macular and pink, it becomes maculopapular and darker. In about 4 days, the lesions become petechial and may coalesce to form large hemorrhagic areas that later ulcerate
Neurologic symptoms include headache, restlessness, insomnia, delirium, and coma, all indicative of encephalitis. Hypotension develops in severe cases. Hepatomegaly may be present, but jaundice is infrequent. Localized pneumonitis may occur. Untreated patients may develop pneumonia, tissue necrosis, and circulatory failure, with such sequelae as brain and heart damage. Cardiac arrest with sudden death occasionally occurs in fulminant cases.
Cytopathologic techniques
Cytopathology is the study of cells from various body sites to determine the cause or nature of disease.
Applications of cytopathology:
- Screening for the early detection of asymptomatic cancer
2. Diagnosis of symptomatic cancer
3. Surveillance of patients treated for cancer
Cytopathologic methods
There are different cytopathologic methods including:
1. Fine-needle aspiration cytology (FNAC) -In FNAC, cells are obtained by aspirating the diseased organ using a very thin needle under negative pressure.
Superficial organs (e.g. thyroid, breast, lymph nodes, skin and soft tissues) can be easily aspirated.
Deep organs, such as the lung, mediastinum, liver, pancreas, kidney, adrenal gland, and retroperitoneum are aspirated with guidance by fluoroscopy, ultrasound or CT scan.
- Exfoliative cytology
Refers to the examination of cells that are shed spontaneously into body fluids or secretions. Examples include sputum, cerebrospinal fluid, urine, effusions in body cavities (pleura, pericardium, peritoneum), nipple discharge and vaginal discharge.
- Abrasive cytology
Refers to methods by which cells are dislodged by various tools from body surfaces (skin, mucous membranes, and serous membranes). E.g. preparation of cervical smears with a spatula or a small brush to detect cancer of the uterine cervix at early stages.