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General Pathology

Iron deficiency anaemia.

Absorption of iron is affected by :
- Iron stores.
- Rate of erythropoiesis
- Acid pH aids absorption.
- Phosphates and phytates in diet impair absorption.

Causes  of deficiency:

- Increased demand:
o    Growth (in children)
o    Menstruation, Pregnancy, lactation.
- Inadequate intake and absorption.
o    Dietary deficiency.
o    Achlorhydria or gastrectomy.
o    Malabsorption states.

- Chronic blood loss
o    Peptic ulcer, bleeding piles
o    Menorrhagia.
o    Hook worm infestation

Features:
- Anaemia.
- Koilonychia.
- Atrophic glossitis and angular stomatitis.
- Dysphagia-Plummer Vinson syndrome.

Blood findings:

- Microcytjc_hypochromic cells, ring cells and pessary cells.
- Anisocytosis and poikilocytosis.
- Low MCV. MCH and MCHC.
- Serum iron is low but iron binding capacity is increased

Bone marrow

Erythroid hyperplasia with imcronormoblasts. Iron stains reveal depleted stores


Differential  diagnosis .-

- Sideroblastic anaemia which is also microcytic hypochromic  but there is excess iron in the erythroid cells .Some are pyridoxine responsive.
- (ii) Thalassaemia
 

Keratoses (Horny Growth)
1. Seborrheic keratosis
is a common benign epidermal tumor composed of basaloid (basal cell-like) cells with increased pigmentation that produce a raised, pigmented, "stuck-on" appearance on the skin of middle-aged individuals.
 - they can easily be scraped from the skin's surface.
 - frequently enlarge of multiply following hormonal therapy.
 - sudden appearance of large numbers of Seborrheic keratosis is a possible indication of a malignancy of the gastrointestinal tract (Leser-Trelat sign).

 2. An actinic keratosis is a pre-malignant skin lesion induced by ultraviolet light damage.
 - sun exposed areas.
 - parakeratosis and atypia (dysplasia) of the keratinocytes.
 - solar damage to underlying elastic and collagen tissue (solar elastosis).
 - may progress to squamous carcinoma in situ (Bowen's disease) or invasive cancer.

 3. A keratoacanthoma is characterized by the rapid growth of a crateriform lesion in 3 to 6
weeks usually on the face or upper extremity.
 - it eventually regresses and involutes with scarring.
 - commonly confused with a well-differentiated squamous cell carcinoma. 

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.

Congestive heart failure (CHF)
A. Left-sided CHF

1. May result from nearly any heart disease affecting the left ventricle (e.g., ischemic heart disease, hypertension, valvular disease).
2. Common signs and symptoms include:
a. Dyspnea (shortness of breath) exacerbated by exertion.
b. Paroxysmal nocturnal dyspnea.
c. Orthopnea.
d. Tachypnea.
e. Pleural effusion.
f. Consequences include pulmonary edema.

B. Right-sided CHF

1. The most common cause of right heart failure is left heart failure. It uncommonly occurs in isolation. Other causes include left-sided lesions (mitral stenosis), pulmonary hypertension, cardiomyopathy, and tricuspid or pulmonary valvular disease.
2. Frequently presents with peripheral edema, especially in the ankles and feet (i.e., dependent edema), enlarged liver or spleen, and distention of the neck veins.

Eosinophilia:
Causes

-Allergic disorders.
-Parasitic infection.
-Skin diseases.
-Pulmonary eosinophilia.
-Myeloproliferative lesions and Hodgkin's disease.

FUNGAL INFECTION

Mucormycosis (Zygomycosis; Phycomycosis)

Infection with tissue invasion by broad, nonseptate, irregularly shaped hyphae of diverse fungal species, including Rhizopus, Rhizomucor, Absidia, and Basidiobolus.

Infection is most common in immunosuppressed persons, in patients with poorly controlled diabetes, and in patients receiving the iron-chelating drug desferrioxamine.

Symptoms and Signs

Rhinocerebral mucormycosis is the most common form, but primary cutaneous, pulmonary, or GI lesions sometimes develop, and hematogenous dissemination to other sites can occur. Rhinocerebral infections are usually fulminant and frequently fatal. Necrotic lesions usually appear on the nasal mucosa or sometimes the palate.

Autopsy

Autopsy is examination of the dead body to identify the cause of death. This can be for forensic or clinical purposes.

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