NEET MDS Lessons
General Pathology
SPIROCHETAL DISEASE
Syphilis
A contagious systemic disease caused by the spirochete Treponema pallidum, characterized by sequential clinical stages and by years of latency.
ACQUIRED SYPHILIS
T. pallidum is a delicate spiral organism about 0.25 µm wide and from 5 to 20 µm long, identified by characteristic morphology and motility with a darkfield microscope or fluorescent techniques
In acquired syphilis, T. pallidum enters through the mucous membranes or skin, reaches the regional lymph nodes within hours, and rapidly disseminates throughout the body. In all stages of disease, perivascular infiltration of lymphocytes, plasma cells, and, later, fibroblasts causes swelling and proliferation of the endothelium of the smaller blood vessels, leading to endarteritis obliterans.
In late syphilis, T. pallidum elicits a granulomatous-like (gummatous) reaction causing masses, ulcerations, and necrosis. Inflammation may subside despite progressive damage, especially in the cardiovascular and central nervous systems.
The CNS is invaded early in the infection. During the secondary stage of the disease, > 30% of patients have abnormal CSF and may have symptoms of meningitis
Symptoms, Signs, and Course
The incubation period of primary syphilis can vary from 1 to 13 wk but is usually from 3 to 4 wk. The disease may present at any stage and long after the initial infection
Primary stage: The primary lesion, or chancre generally evolves and heals within 4 to 8 wk in untreated patients. After inoculation, a red papule quickly erodes to form a painless ulcer with an indurated base that, when abraded, exudes a clear serum containing numerous spirochetes
The regional lymph nodes usually enlarge painlessly and are firm, discrete, and nontender. Chancres occur on the penis, anus, and rectum in men and on the vulva, cervix, and perineum in women. Chancres may also occur on the lips or the oropharyngeal or anogenital mucous membranes.
Secondary stage: Cutaneous rashes usually appear within 6 to 12 wk after infection and are most florid after 3 to 4 mo.
Frequently, generalized, nontender, firm, discrete lymphadenopathy and hepatosplenomegaly are palpable. Over 80% of patients have mucocutaneous lesions, 50% have generalized lymphadenopathy, and about 10% have lesions of the eyes (uveitis), bones (periostitis), joints, meninges, kidneys (glomerulitis), liver, and spleen.
Acute syphilitic meningitis may develop, with headache, neck stiffness, cranial nerve lesions, deafness, and, occasionally, papilledema.
Condyloma lata--hypertrophic, flattened, dull pink or gray papules at the mucocutaneous junctions and in moist areas of the skin--are extremely infectious. Hair often falls out in patches, leaving a moth-eaten appearance (alopecia areata).
Latent stage
In the early latent period (< 2 yr after infection), infectious mucocutaneous relapses may occur, but after 2 yr contagious lesions rarely develop, and the patient appears normal. About 1/3 of untreated persons develop late syphilis
Late or tertiary stage: Lesions may be clinically described as (1) benign tertiary syphilis of the skin, bone, and viscera, (2) cardiovascular syphilis, or (3) neurosyphilis.
The typical lesion is a gumma, an inflammatory mass that evolves to necrosis and fibrosis and that is frequently localized but may diffusely infiltrate an organ or tissue
Benign tertiary syphilis of the bones results in either periostitis with bone formation or osteitis with destructive lesions causing a deep, boring pain, characteristically worse at night. A lump or swelling may be palpable.
Cardiovascular syphilis: A dilated, usually fusiform aneurysm of the ascending or transverse aorta, narrowing of the coronary ostia, or aortic valvular insufficiency usually appears 10 to 25 yr after the initial infection
Neurosyphilis
In meningovascular neurosyphilis, brain involvement is signaled by headache, dizziness, poor concentration, lassitude, insomnia, neck stiffness, and blurred vision. Mental confusion, epileptiform attacks, papilledema, aphasia, and mono- or hemiplegia may also occur
Diagnosis:
Two classes of serologic tests for syphilis (STS) aid in diagnosing syphilis and other related treponemal diseases: screening, nontreponemal tests using lipoid antigens detect syphilitic reagin and include the Venereal Disease Research Laboratory (VDRL) and the rapid plasma reagin (RPR) tests. Specific treponemal tests detect antitreponemal antibodies and include fluorescent treponemal antibody absorption (FTA-ABS) test, microhemagglutination assay for antibodies to T. pallidum (MHA-TP), and Treponema pallidum hemagglutination assay (TPHA).
In darkfield microscopy, light is directed obliquely through the slide so that rays striking the spirochetes cause them to appear as bright, motile, narrow coils against a dark background
Bacterial meningitis (pyogenic, suppurative infections)
1. Common causes include:
a. Escherichia coli in newborns.
b. Haemophilus influenzae in infants and children.
c. Neisseria meningitides in young adults.
d. Streptococcus pneumoniae and Listeria monocytogenes in older adults.
Clinical findings include severe headache, irritability, fever, and a stiff neck.
a. A spinal tap shows CSF fluid that is cloudy or purulent and is under increased pressure. There is also an increase in protein and a decrease in glucose levels.
3. Can be fatal if left untreated.
Thyroid goitres
A goitre is any enlargement of part or whole of the thyroid gland. There are two types:
1. Toxic goitre, i.e. goitre associated with thyrotoxicosis.
2. Non-toxic goitre, i.e. goitre associated with normal or reduced levels of thyroid hormones.
Toxic goitre
Graves disease
This is the most common cause of toxic goitre
Toxic multinodular goitre
This results from the development of hyperthyroidism in a multinodular goitre
Non-toxic goitres
Diffuse non-toxic goitre (simple goitre)
This diffuse enlargement of the thyroid gland is classified into:
Endemic goitre—due to iodine deficiency. Endemic goiter occurs in geographic areas (typically mountainous)) where the soil, water, and food supply contain little iodine. The term endemic is used when goiters are present in more than 10% of the population in a given region. With increasing availability of dietary iodine supplementation, the frequency and severity of endemic goiter have declined significantly. Sporadic goiter is less common than endemic goiter. The condition is more common in females than in males, with a peak incidence in puberty or young adult life, when there is an
increased physiologic demand for T4.
Sporadic goitre—caused by goitrogenic agents (substances that induce goitre formation) or familial in origin. Examples of goitrogenic agents include certain cabbage species, because of their thiourea content, and specific drugs or chemicals, such as iodide, paraminosalicylic acid and drugs used in the treatment of thyrotoxicosis. Familial cases show inherited autosomal recessive traits, which interfere with hormone synthesis via various enzyme pathways (these are dyshormonogenic goitres).
Hereditary enzymatic defects interfering with thyroid hormone synthesis (dyshormonogenetic goiter).
Physiological goitre—enlargement of the thyroid gland in females during puberty or pregnancy; the reason is unclear.
Multinodular goitre
This is the most common cause of thyroid enlargement and is seen particularly in the elderly (nearly all simple goitres eventually become multinodular). The exact aetiology is uncertain but it may represent an uneven responsiveness of various parts of the thyroid to fluctuating TSH levels over a period of many years.
Morphological features are:
• Irregular hyperplastic enlargement of the entire thyroid gland due to the development of wellcircumscribed nodules of varying size.
• Larger nodules filled with brown, gelatinous colloid; consequently, it is often termed multinodular colloid goitres.
Clinical features
- A large neck mass, goiters may also cause airway obstruction, dysphagia, and compression of large vessels in the neck and upper thorax.
- A hyperfunctioning ("toxic") nodule may develop within a long-standing goiter, resulting in hyperthyroidism. This condition is not accompanied by the infiltrative ophthalmopathy and dermopathy.
- Less commonly, there may be hypothyroidism.
Hematological examination
This is a method by which abnormalities of the cells of the blood and their precursors in the bone marrow are investigated to diagnose the different kinds of anemia & leukemia.
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
AMYLOIDOSIS
Definition. Extra cellular deposition of an eosinophilic hyaline homogenous material in Various organs, occurring in a variety of clinical states.
Staining reactions
Iodine :- Brown, turning blue on addition of H2SO4 (gross and microscopic Stain).
P.A.S. – Positive (Magenta pink).
Congo Red -Orange red which on polarisation gives green birefringence.
Von Geison's –Khaki colour.
Thioflavin T -Yellow fluorescence.
Amyloid is called typical if it given the above staining reactions Other wise it is termed atypical or para-amyloid.
Classification
1. Systemic amyloidosis associated with underlying disease (secondary),
(A) Chronic infections like
- Tuberculosis.
- Bronchiectasis.
- Lung abscess.
- Osteomyelitis.
- Syphilis.
(B) Chronic inflammations of varied etiology:
- Rheumatoid arthritis.
- Ulcerative colitis.
- Regional enteritis.
- Lupus erythematosus.
(C) Neoplastic proliferations:
- Of immune system – Multiple myeloma, Hodgkin’s disease.
- Cancers like Renal cell carcinoma etc.
II Systemic primary amyloidosis with no underlying cause.
III Heredofamilial types.
- Amyloidosis with mediterranean fever.
- Amyloid polyneuropathy.
- Amyloid nephrophathy
- Familial cardiac amyloidosis
- Familial cutaneous amyloid.
- Lattice corneal dystrophy
IV. Localised amyloidosis:
- Senile - in heart, brain, seminal vesicles.
- Amyloidoma of tongue, bronchial tree, skin.
- In islets of Langerhans in Diabetes mellitus.
- In medullary thyroid carcinoma.
Deposition sites
In relation to reticulin and collagen fibres and to basement, membranes especially
subendothelial.
Organs involved commonly are :
Secondary amyloidosis
- Liver.
- Spleen.
- Kidney
- Lymph nodes.
- Adrenals.
Primary amyloidosis
- Heart
- Tongue and gingiva.
- Gastro intestinal tract.
- Lung.
- Wall of small vessels.
Nature and pathogenesis of amyloid
It is primarily made up of protein arranged in two patterns
- There are filaments twisted together to from the fibrils. These chemically resemble light chains of immunoglobulins
- Rods composed of stacked rings. These are made up of alpha globulin components of plasma proteins (P-components)
- In addition to these, extracts of crude amyloid contain mucopolysacharides complement and gamma globulins.
- Origin of amyloid :- current concept is that it is a direct product of cells of the immune sustem with some abnormality in their immune response
The abnormality may be due to :
- A genetic enzyme defect.
- Prolonged antigenic challenge.
- Neoplastic transformation
- Supression of normal. Response as in induced tolerance.
Pernicious anaemia
The special features are:
- Due to intrinsic factor deficiency
- Gastric atrophy with histamine fast achlorhydria
- Genetic basis (racial distribution and blood group A).
- Seen with auto immune disorders.
- Antibodies to parietal cells and to intrinsic factors are seen