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General Pathology - NEETMDS- courses
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General Pathology

Liver cirrhosis

It is a chronic, progressive diffuse process characterized by 
a. Hepatocellular necrosis           
b. Replacement by fibrosis and inflammation 
c. Hyperplasia of surviving liver cells forming regenerating nodules 
d. Vascular derangement. 

All these changes lead to loss of the normal liver architecture. 

Pathology of cirrhosis
At first the liver is enlarged or of normal size. Late in the disease, it is reduced in size and weight. 
Consistency- Firm. 
Colour -May be yellow (fatty change), red (congestion), green (cholestaisis), or pale gray (recent nodules due to absence of pigment). 

Morphologically  According to the size of these nodules, cirrhosis can be classified
    
    Micronodular (regular) cirrhosis. Small nodules 2-3 mm.in diameter.
    Macronodular (irregular) cirrhosis, nodules up to one cm in diameter.
    Mixed cirrhosis is the end stage of all types of cirrhosis
    
Microscopic picture 

1 Regenerating nodulesn- Proliferated hepatocytes arranged in thick plates and separated by blood sinusoids.  Central vein in abnormal sites (eccentric) - Hepatocytes may be small , large , or binucleated 

2- Fibrosis- It replaces damaged hepatocytes. It develops at certain sites:-
a-perivenular    b -perisinusoidal    c -pericellular  and d -in relation to portal tracts.

- It may be young, cellular and highly vascular or mature with diminished vasculsarity. It encloses groups of hepatocytes, lobules or regenerating nodules.

-As a result of hepatocyte injury and fibrosis, there’s loss of normal liver architecture including the lobular and acinar pattern as well as the liver cell plates 

3- Bile ductular proliferation:- Occurs in the fibrous septa.Focal choestaisis with feathery degeneration of hepatocytes occur at the margins of regenerating nodules. It becomes diffuse terminally.  

4- Inflammatory cells:-   Lymphocytes, macrophages and plasma cells infiltrate the fibrous septa and regenerating nodules 

Etiological classification of cirrhosis

Congenital Occurs at childhood
- congenital syphilis   
  
Hereditary diseases:
a. Primary idiopathic haemochromatosis      b. Thalassemia      c. Wilson’s disease      d.α 1-antitrypsin deficien e. glycogen storage disease

Acquired

-Cryptogenic (10-50%).             
-Alcoholic (30-70%)
-Post viral  (15-20%)                
- Biliary cirrhosis (16%) primary or secondary. 

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 

FUNGAL INFECTION

Aspergillosis

Opportunistic infections caused by Aspergillus sp and inhaled as mold conidia, leading to hyphal growth and invasion of blood vessels, hemorrhagic necrosis, infarction, and potential dissemination to other sites in susceptible patients.

Symptoms and Signs: Noninvasive or, rarely, minimally locally invasive colonization of preexisting cavitary pulmonary lesions also may occur in the form of fungus ball (aspergilloma) formation or chronic progressive aspergillosis.

Primary superficial invasive aspergillosis is uncommon but may occur in burns, beneath occlusive dressings, after corneal trauma (keratitis), or in the sinuses, nose, or ear canal.

Invasive pulmonary aspergillosis usually extends rapidly, causing progressive, ultimately fatal respiratory failure unless treated promptly and aggressively. A. fumigatus is the most common causative species.

 Extrapulmonary disseminated aspergillosis may involve the liver, kidneys, brain, or other tissues and is usually fatal. Primary invasive aspergillosis may also begin as an invasive sinusitis, usually caused by A. flavus, presenting as fever with rhinitis and headache

Herpes zoster, or shingles
 - represents reactivation of a latent varicella-zoster infection.
 - virus lies dormant in sensory dorsal root ganglia and when activated involves the distribution (dermatome) of the sensory nerve with a painful vesicular eruption.
 - trigeminal verve distribution → Ramsay Hunt syndrome
 - may indicate the presence of advanced neoplastic disease or be a complication of chemotherapy.

Lysosomal (lipid) storage diseases
- Genetic transmission: autosomal recessive.
- This group of diseases is characterized by a deficiency of a particular lysosomal enzyme. This results in an accumulation of the metabolite, which would have otherwise been degraded by the presence of normal levels of this specific enzyme.

Diseases include:
Gaucher’s disease
(1) Deficient enzyme: glucocerebrosidase.
(2) Metabolite that accumulates: glucocerebroside.
(3) Important cells affected: macrophages.

Tay-Sachs disease
(1) Deficient enzyme: hexosaminidase A.
(2) Metabolite that accumulates: GM2 ganglioside.
(3) Important cells affected: neurons.
(4) Symptoms include motor and mental deterioration, blindness, and dementia.
(5) Common in the Ashkenazi Jews.

Niemann-Pick disease
(1) Deficient enzyme: sphingomyelinase.
(2) Metabolite that accumulates: sphingomyelin.
(3) Important cells affected: neurons.

PARASITIC DISEASES

AMEBIASIS (Entamebiasis)

Infection of the colon with Entamoeba histolytica, which is commonly asymptomatic but may produce clinical manifestations ranging from mild diarrhea to severe dysentery.

Etiology and Pathogenesis 

Amebiasis is a protozoan infection of the lower GI tract. E. histolytica exists in two forms: the trophozoite and the cyst.

Two species of Entamoeba are morphologically indistinguishable: E. histolytica is pathogenic and E. dispar harmlessly colonizes the colon. Amebas adhere to and kill colonic epithelial cells and cause dysentery with blood and mucus in the stool. Amebas also secrete proteases that degrade the extracellular matrix and permit invasion into the bowel wall and beyond. Amebas can spread via the portal circulation and cause necrotic liver abscesses.

Symptoms and Signs 

Most infected persons are asymptomatic but chronically pass cysts in stools. Symptoms that occur with tissue invasion include intermittent diarrhea and constipation, flatulence, and cramping abdominal pain. There may be tenderness over the liver and ascending colon, and the stools may contain mucus and blood.

Amebic dysentery, common in the tropics but uncommon in temperate climates, is characterized by episodes of frequent (semi)liquid stools that often contain blood, mucus, and live trophozoites.

Chronic infection commonly mimics inflammatory bowel disease and presents as intermittent nondysenteric diarrhea with abdominal pain, mucus, flatulence, and weight loss.

Metastatic disease originates in the colon and can involve any organ, but a liver abscess, usually single and in the right lobe, is the most common
 

Monocytosis:
Causes

-Infections causing lymphocytosis, especialy tuberculosis and typhoid. 
-Monocytic leukaemia.
-Some auto immune diseases.

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