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General Pathology

Fulminant hepatitis

Fulminant hepatitis leads to submassive and massive hepatic necrosis. 
a. Etiology. HAV, HBV, HCV, delta virus (HDV) superinfection, HEV, chloroform, carbon tetrachloride, isoniazid, halothane, and other drugs (acetaminophen overdose) all may cause fulminant hepatitis.
b. Clinical features include progressive hepatic dysfunction with a mortality of 25%-90%.
c. Pathology

(1) Grossly, one sees progressive shrinkage of the liver as the parenchyma is destroyed. 

Langerhans cell granulomatosis (histocytosis X)
a. A group of diseases that are caused by the proliferation of Langerhans’ cells (previously known as histocytes).
b. Most commonly causes bone lesions; however, other tissues can be affected.
c. Histologic findings include Langerhans’ cells containing Birbeck granules and eosinophils.

d. Three types:
(1) Letterer-Siwe disease—an acute, disseminated form that is fatal in infants.
(2) Hand-Schüller-Christian disease—a chronic, disseminated form that has a better prognosis than LettererSiwe disease. It usually presents
before the age of 5 and is characterized by a triad of symptoms:
(a) Bone lesions—found in skull, mandible (loose teeth).
(b) Exophthalmos.
(c) Diabetes insipidus.
(3) Eosinophilic granuloma of bone—a localized, least severe form of the three. Lesions may heal without treatment.
(a) Most commonly occurs in young adults.
(b) Lesions in the mandible may cause loose teeth.

N. meningiditis

Major cause of fulminant bacteremia and meningitis.  Has a unique polysaccharide capsule.  It is spread person to person by the respiratory route.  Frequently carried in nasopharynx, and carriage rates increased by close quarters.  Special risk in closed populations (college dorms) and in people lacking complement.  Sub-saharan Africa has a “meningitis belt.”

Pathogenesis is caused by adherence factors that attach to non-ciliated nasopharyngeal epithelium. These factors include pili which promote the intial epithelial (and erythrocyte) attachment, and Opa/Opc surface binding proteins.

Adherence stimulates engulfment of bacteria by epithelial cells.  Transported to basolateral surface.

The polysaccharide capsule is a major virulence factor that prevents phagocytosis and lysis. 

A lipo-oligosaccharide endotoxin also contributes to sepsis.

Smallpox (variola)
 
- vesicles are well synchronized (same stage of development) and cover the skin and mucous membranes.
 - vesicles rupture and leave pock marks with permanent scarring.

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.

Paget Disease (Osteitis Deformans) 

This unique bone disease is characterized by repetitive episodes of exaggerated, regional osteoclastic activity (osteolytic stage), followed by exuberant bone formation (mixed osteoclastic-osteoblastic stage), and finally by exhaustion of cellular activity (osteosclerotic stage). The net effect of this process is a gain in bone mass; however, the newly formed bone is disordered and lacks strength. Paget disease usually does not occur until mid-adulthood but becomes progressively more common thereafter. The pathognomonic histologic feature is a mosaic pattern of lamellar bone (likened to a jigsaw puzzle) due to prominent cement lines that haphazardly fuse units of lamellar bone. (Fig. 12-5) The axial skeleton and proximal femur are involved in the majority of cases. In patients with extensive disease, hypervascularity of the marrow spaces can result in high-output congestive heart failure. Cranial nerves impingement also occurs and can lead to head ache and auditory disturbances. Rarely Paget disease is complicated by bone sarcoma (usually osteogenic). 

Psoriasis is a chronic disorder characterized by scaly, erythematous plaques, which histologically are secondary to epidermal proliferation.
 - genetic factors (HLA relationships), environmental (physical injury, infection, drugs, photosensitivity), abnormal cellular proliferation (deregulation of epidermal proliferation) and microcirculatory changes in the papillary dermis (diapedesis of neutrophils into the epidermis) are all interrelated.
 - the plaques of psoriasis are characteristically well-demarcated pink or salmon colored lesions covered by a loosely-adherent silver-white scale which, when picked off, reveals pinpoint bleeding sites (Auspitz sign).
 - the nail changes in psoriasis include pitting, dimpling, thickening and crumbling with a yellowish-brown discoloration of the nail plate.
 - the characteristic histologic features of psoriasis include:
 - hyperkeratosis
 - absence of the granulosa cells (present in lichen planus).
 - parakeratosis
 - regular, club-shaped elongation of the rete pegs (irregular and saw toothed in lichen planus) with vessel proliferation in the papillary dermis (reason for the bleeding associated with Auspitz sign).
 - characteristic subcorneal collection of neutrophils called a Munro's microabscess (diapedesis from vessels in papillary dermi).
 - 7% develop HLA B27 positive psoriatic arthritis

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