NEET MDS Lessons
General Pathology
Osteomyelitis
This refers to inflammation of the bone and related marrow cavity almost always due to infection. Osteomyelitis can be acute or a chronic. The most common etiologic agents are pyogenic bacteria and Mycobacterium tuberculosis.
Pyogenic Osteomyelitis
The offending organisms reach the bone by one of three routes:
1. Hematogenous dissemination (most common)
2. Extension from a nearby infection (in adjacent joint or soft tissue)
3. Traumatic implantation of bacteria (as after compound fractures or orthopedic procedures). Staphylococcus aureus is the most frequent cause. Mixed bacterial infections, including anaerobes, are responsible for osteomyelitis complicating bone trauma. In as many as 50% of cases, no organisms can be isolated.
Pathologic features
• The offending bacteria proliferate & induce an acute inflammatory reaction.
• Entrapped bone undergoes early necrosis; the dead bone is called sequestrum.
• The inflammation with its bacteria can permeate the Haversian systems to reach the periosteum. In children, the periosteum is loosely attached to the cortex; therefore, sizable subperiosteal abscesses can form and extend for long distances along the bone surface.
• Lifting of the periosteum further impairs the blood supply to the affected region, and both suppurative and ischemic injury can cause segmental bone necrosis.
• Rupture of the periosteum can lead to an abscess in the surrounding soft tissue and eventually the formation of cutaneous draining sinus. Sometimes the sequestrum crumbles and passes through the sinus tract.
• In infants (uncommonly in adults), epiphyseal infection can spread into the adjoining joint to produce suppurative arthritis, sometimes with extensive destruction of the articular cartilage and permanent disability.
• After the first week of infection chronic inflammatory cells become more numerous. Leukocyte cytokine release stimulates osteoclastic bone resorption, fibrous tissue ingrowth, and bone formation in the periphery, this occurs as a shell of living tissue (involucrum) around a segment of dead bone. Viable organisms can persist in the sequestrum for years after the original infection.
Chronicity may develop when there is delay in diagnosis, extensive bone necrosis, and improper management.
Complications of chronic osteomyelitis include
1. A source of acute exacerbations
2. Pathologic fracture
3. Secondary amyloidosis
4. Endocarditis
5. Development of squamous cell carcinoma in the sinus tract (rarely osteosarcoma).
Tuberculous Osteomyelitis
Bone infection complicates up to 3% of those with pulmonary tuberculosis. Young adults or children are usually affected. The organisms usually reach the bone hematogenously. The long bones and vertebrae are favored sites. The lesions are often solitary (multifocal in AIDS patients). The infection often spreads from the initial site of bacterial deposition (the synovium of the vertebrae, hip, knee, ankle, elbow, wrist, etc) into the adjacent epiphysis, where it causes typical granulomatous inflammation with caseous necrosis and extensive
bone destruction. Tuberculosis of the vertebral bodies (Pott disease), is an important form of osteomyelitis.
Infection at this site causes vertebral deformity and collapse, with secondary neurologic deficits. Extension of the infection to the adjacent soft tissues with the development of psoas muscle abscesses is fairly common in Pott disease. Advanced cases are associated with cutaneous sinuses, which cause secondary bacterial infections. Diagnosis is established by synovial fluid direct examination, culture or PCR
SMALL INTESTINE
Congenital anomalies
1. Meckel's diverticulum (a true diverticulum) is due to persistence of the omphalomesenteric vitelline duct.
2. Atresia is a congenital absence of a region of bowel, leaving a blind pouch or solid fibrous cord.
3. Stenosis refers to a narrowing of any region of the gastrointestinal tract, which may cause obstruction.
4. Duodenal diverticula are areas of congenital weakness permitting saccular enlargement. The duodenum is the most common region of the small bowel to contain diverticula.
5. Diverticula of jejunum and ileum are herniations of mucosa and submucosa at points where the mesenteric vessels and nerves enter.
Infections
1. Bacterial enterocolitis may be caused by the ingestion of preformed bacterial toxins, producing symptoms ranging from severe but transient nausea, vomiting, and diarrhea (Staphylococcus aureus toxin) to lethal paralysis (Clostridium botulinum toxin). Ingestion of toxigenic bacteria with colonization of the gut (e.g., Vibrio cholera, toxigenic E. coli, various species of Campylobacter jejuni, Shigella, salmonel
Yersinia, and many others) is another potential cause.
2. Nonbacterial gastroenterocolitis
a. Viral
(1) Rotavirus (children)
(2) Parvovirus (adults)
b. Fungal-Candida
c. Parasitic
(1 ) Entamoeba histolytica
(2) Giardia lamblia
3. In HIV patients. Causes of infectious diarrhea in HIV patients include Cryptosporidium, Microsporidia, isospora belli, CMV, and M. avium-intracellulare.
C. Malabsorption is defined as impaired intestinal absorption of dietary constituents.
Clinical features include diarrhea,steatorrhea, weakness, lassitude, and weight loss. Steatorrhea results in deficiency of fat-soluble vitamins (A, D, E, K) and calcium.
1. Celiac sprue
a. Etiology. Celiac sprue (nontropical sprue or gluten enteropathy) is caused by an allergic, immunologic, or toxic reaction to the gliadin component of gluten. There is a genetic predisposition.
Symptoms:
– Steatorrhea, abdominal distention, flatulence, fatigue, and weight loss
Complications:
– Iron and vitamin deficiency
– Risk of lymphoma (T-cell type)
Extraintestinal manifestation:
– Dermatitis herpetiformis (a pruritic papulovesicular rash with IgA deposits at the dermoepidermal junction)
2. Tropical sprue
Etiology. Tropical sprue is of unknown etiology, but may be caused by enterotoxigenic E. coli.
3. Disaccharidase deficiency is due to a deficiency of brush border enzymes. Lactase deficiency is most common.
4. Diverticulosis Coli
- Acquired colonic diverticula are present in nearly half of the population over the age of 50
- Diverticula are associated with low-fiber, low-residue diets
- Etiology is most likely high intraluminal pressure required for propulsion of hard, small stools
- Complications include hemorrhage, acute diverticulitis, perforation, fistula formation
Obstructive lesions
Hernias cause 15% of small intestinal obstruction. They are due to a protrusion of a serosa-lined sac through a weakness in the wall of the peritoneal cavity. They occur most commonly at the inguinal and femoral canals, at the umbilicus, and with scars. They may lead to entrapment, incarceration, and strangulation of the bowel.
Tumors of the small bowel account for only 5% of gastrointestinal tumors.
Benign tumors in descending order of frequency include:
leiomyomas, lipomas, adenomas (polyps), angiomas, and fibromas. Adenomatous polyps are most common in the stomach and duodenum and may be single or multiple, sessile or pedunculated. The larger the polyp, the greater the incidence of malignant transformation.
Malignant tumors, in descending order of frequency, include: endocrine cell tumors, lymphomas, adenocarcinomas, and leiomyosarcomas.
Idiopathic Inflammatory Bowel Disease (IBD)
- Chronic, relapsing, idiopathic inflamamtory disease of the GI tract
Crohn’s Disease
– Transmural granulomatous disease affecting any portion of the GI tract
Ulcerative Colitis
– Superficial, non-granulomatous inflammatory disease restricted to the colon
Ulcerative Colitis
- Bloody mucoid diarrhea, rarely toxic megacolon
- Can begin at any age, peaks at 20-25 years
- Annual incidence of ~10 per 100,000 in US
- Negligible risk of cancer in the first 10 years, but 1% per year risk of cancer thereafter
- Good response to total colectomy if medical therapy fails
Macroscopic
- Normal serosa
- Bowel normal thickness
- Continuous disease
- Confluent mucosal ulceration
- Pseudopolyp formation
Microscopic
- Crypt distortion + shortening
- Paneth cell metaplasia
- Diffuse mucosal inflammation
- Crypt abscesses
- Mucin depletion
- Mucosal ulceration
Crohn’s Disease
- Variable and elusive clinical presentation with diarrhea, pain, weight loss, anorexia, fever
- Can begin at any age, peaks at 15-25 years
- Annual incidence of ~3 per 100,000 in US
- Many GI complications and extracolonic manifestations
- Risk of cancer less than in UC
- Poor response to surgery
Macroscopic
Fat wrapping
Thickened bowel wall
Skip Lesions
Stricture formation
Cobblestoned mucosa
Ulceration
Microscopic
- Cryptitis and crypt abscesses
- Transmural inflammation
- Lymphoid aggregates +/- granulomas
- “Crohn’s rosary”
- Fissuring
- Neuromuscular hyperplasia
Clinical genetics (cytogenetics),
This is a method in which inherited chromosomal abnormalities in the germ cells or acquired chromosomal abnormalities in somatic cells are investigated using the techniques of molecular biology.
CARCINOMA IN SITU
Epithelial malignancy which has not yet invaded even -the local confines viz basement membrane is termed as carcinoma in situ (intra epithelial neoplasia, pre-invasive cancer)
This lesion merges morphologically with severe dysplasia
Common sites for carcinoma-in-situ :
- Cervical squamous epithelium
- Oropharynx
- Bronchial epithelium.
- Breast ducts and lobules.
- Skin, in the form of Bowen's disease.
- Glans penis and vulva in the form of Erythroplasia of Queyrat
Molecular techniques
Different molecular techniques such as fluorescent in situ hybridization, Southern blot, etc... can be used to detect genetic diseases.
THE ADRENAL GLANDS
ADRENAL CORTEX
The adrenal cortex synthesizes three different types of steroids:
1. Glucocorticoids (principally cortisol), which are synthesized primarily in the zona fasciculata
2. Mineralocorticoids, the most important being aldosterone, which is generated in the zona glomerulosa; and
3. Sex steroids (estrogens and androgens), which are produced largely in the zona reticularis.
ADRENAL MEDULLA
The adrenal medulla is populated by cells derived from the neural crest (chromaffin cells) and their supporting (sustentacular) cells.
They secrete catecholamines in response to signals from preganglionic nerve fibers inthe sympathetic nervous system.
IMMUNITY AND RESISTANCE TO INFECTION
Body's resistance to infection depends upon:
I. Defence mechanisms at surfaces and portals of entry.
II. Nonspecific or innate immunity
Ill. Specific immune response.