Hereditary spherocytosis.

Functionally normal cells which are destroyed .in spleen because of the structural abnormality. It is transmitted as an autosomal dominant trait 

Congenital hemolytic anemia due to genetically determined abnormal spectrin and ankyrin molecules, leading to defects in red blood cell membrane, causing spherical shape and lack of plasticity
Red blood cells become trapped within spleen and have less than usual 120 day lifespan
Splenic function is normal
Osmotic fragility: increased; basis for diagnostic testing 

Description

Firm, deep red tissue, thin capsule, no grossly identifiable malpighian follicles, 100-1000g
Peripheral blood images
Marked congestion in cords
Sinuses appear empty but actually contain ghost red blood cells
May have prominent endothelial lined sinuses, hemosiderin deposition, erythrophagocytosis

 LUNG ABSCESS  Lung abscess is a localised area of necrosis of lung tissue with suppuration.

 It is of 2 types:

 - Primary lung abscess that develops in an otherwise normal lung. The commonest cause is aspiration of infected material.

 - Secondary lung abscess that develops as a complication of some other disease of the lung or from another site

ETIOPATHOGENESIS.

 The microorganisms commonly isolated from the lungs in lung abscess are streptococci, staphylococci and various gram-negative organisms. These are introduced into the lungs from one of the following mechanisms:

 1.   Aspiration of infected foreign material.

 2. Preceding bacterial infection.

 3.  Bronchial obstruction.

 4. Septic embolism.

 5. Miscellaneous (i) Infection in pulmonary infarcts, (ii) Amoebic abscesses, (iii) Trauma to the lungs. (iv) Direct extension from a suppurative focus.

Abscesses may be of variable size from a few millimeters to large cavities, 5 to 6 cm in diameter. The cavity often contains exudate. An acute lung abscess is initially surrounded by acute pneumonia and has poorly-defined ragged wall. With passage of time, the abscess becomes chronic and develops fibrous wall.

Microscopic Examination

The characteristic feature is the destruction of lung parenchyma with suppurative exudate in the lung cavity. The cavity is initially surrounded by acute inflammation in the wall but later there is replacement by exudate of lymphocytes, plasma cells and macrophages. In more chronic cases, there is considerable fibroblastic proliferation forming a fibrocollagenic wall.

ADRENAL INSUFFICIENCY

Adrenocortical hypofunction is either primary (adrenocrtical) or secondary (ACTH deficiency). Primary insufficiency is divided into acute & chronic. 
Acute Adrenocortical Insufficiency occurs most commonly in the following clinical settings
- massive adrenal hemorrhage including  Waterhouse-Friderichsen syndrome 
- Sudden withdrawal of long-term corticosteroid therapy
- Stress in those with chronic adrenal insufficiency 

Massive adrenal hemorrhage may destroy the adrenal cortex sufficiently to cause acute adrenocortical 
insufficiency. This condition may occur 
1. in patients maintained on anticoagulant therapy 
2. in postoperative patients who develop DIC
3. during pregnancy 
4. in patients suffering from overwhelming sepsis (Waterhouse-Friderichsen syndrome) 

Waterhouse-Friderichsen syndrome is a catastrophic syndrome classically associated with Neisseria meningitidis septicemia but can also be caused by other organisms, including Pseudomonas species, pneumococci & Haemophilus influenzae. The pathogenesis of the syndrome remains unclear, but probably involves endotoxin-induced vascular injury with associated DIC.

Chronic adrenocortical insufficiency (Addison disease) results from progressive destruction of the adrenal cortex. More than 90% of all cases are attributable to one of four disorders: 
1. autoimmune adrenalitis (the most common cause; 70% of cases) 
2. tuberculosis &fungal infections 
3. AIDS
4. Metastatic cancers   
In such primary diseases, there is hyperpigmentation of the skin oral mucosa due to high levels of MSH (associated with high levels of ACTH).

Autoimmune adrenalitis is due to autoimmune destruction of steroid-producing cells. It is either isolated associated other autoimmune diseases, such as Hashimoto disease, pernicious anemia, etc. 

Infections, particularly tuberculous and fungal

Tuberculous adrenalitis, which once was responsible for as many as 90% of cases of Addison disease, has become less common with the advent of antituberculous therapy. When present, tuberculous adrenalitis is usually associated with active infection elsewhere, particularly the lungs and genitourinary tract. Among fungi, disseminated infections caused by Histoplasma capsulatum is the main cause. 

AIDS patients are at risk for developing adrenal insufficiency from several infectious (cytomegalovirus, Mycobacterium avium-intracellulare) and noninfectious (Kaposi sarcoma) complications.
 
Metastatic neoplasms: the adrenals are a fairly common site for metastases in persons with disseminated carcinomas. Although adrenal function is preserved in most such patients, the metastatic growths sometimes destroy sufficient adrenal cortex to produce a degree of adrenal insufficiency. Carcinomas of the lung and breast are the major primary sources. 

Secondary Adrenocortical Insufficiency

Any disorder of the hypothalamus and pituitary, such as metastatic cancer, infection, infarction, or irradiation, that reduces the output of ACTH leads to a syndrome of hypoadrenalism having many similarities to Addison disease. In such secondary disease, the hyperpigmentation of primary Addison disease is lacking because melanotropic hormone levels are low. 

Secondary adrenocortical insufficiency is characterized by low serum ACTH and a prompt rise in plasma cortisol levels in response to ACTH administration. 

Pathological features of adrenocortical deficiency 

- The appearance of the adrenal glands varies with the cause of the insufficiency. 
- In secondary hypoadrenalism the adrenals are reduced to small, uniform, thin rim of atrophic yellow cortex that surrounds a central, intact medulla. Histologically, there is atrophy of cortical cells with loss of cytoplasmic lipid, particularly in the zonae fasciculata and reticularis. 
- In primary autoimmune adrenalitis there is also atrophy of the cortex associated with a variable lymphoid infiltrate that may extend into the subjacent medulla. The medulla is otherwise normal.  
- In tuberculosis or fungal diseases there is granulomatous inflammatory reaction. Demonstration of the responsible organism may require the use of special stains.  
- With metastatic carcinoma, the adrenals are enlarged and their normal architecture is obscured by the infiltrating neoplasm.  
 

Neuroblastoma and Related Neoplasms
Neuroblastoma is the second most common solid malignancy of childhood after brain tumors, accounting for up to10% of all pediatric neoplasms. They are most common during the first 5 years of life. Neuroblastomas may occur anywhere along the sympathetic nervous system and occasionally within the brain. Most neuroblastomas are sporadic. Spontaneous regression and spontaneous- or therapy-induced maturation are their unique features.  

Gross features
- The adrenal medulla is the commonest site of neuroblastomas. The remainder occur along the sympathetic chain, mostly in the paravertebral region of the abdomen and posterior mediastinum. 
- They range in size from minute nodules to large masses weighing more than 1 kg. 
- Some tumors are delineated by a fibrous pseudo-capsule, but others invade surrounding structures, including the kidneys, renal vein, vena cava, and the aorta. 
- Sectioning shows soft, gray-tan, brain-like tissue. Areas of necrosis, cystic softening, and hemorrhage may be present in large tumors. 

Microscopic features
- Neuroblastomas are composed of small, primitive-appearing neuroblasts with dark nuclei & scant cytoplasm, g rowing in solid sheets.  
- The background consists of light pinkish fibrillary material corresponding to neuritic processes of the primitive cells. 
- Typically, rosettes can be found in which the tumor cells are concentrically arranged about a central space filled with the fibrillary neurites.
- Supporting features include include immunochemical detection of neuron-specific enolase and ultrastructural demonstration of small, membrane-bound, cytoplasmic catecholamine-containing secretory granules.
- Some neoplasms show signs of maturation, either spontaneous or therapy-induced. Larger ganglion-like cells having more abundant cytoplasm with large vesicular nuclei and prominent nucleoli may be found in tumors admixed with primitive neuroblasts (ganglioneuroblastoma). Further maturation leads to tumors containing many mature ganglion-like cells in the absence of residual neuroblasts (ganglioneuroma). 

Many factors influence prognosis, but the most important are the stage of the tumor and the age of the patient. Children below 1 year of age have a much more favorable outlook than do older children at a comparable stage of disease. 

Miscroscopic features are also an independent prognostic factor; evidence of gangliocytic differentiation is indicative of a "favorable" histology. Amplification of the MYCN oncogene in neuroblastomas is a molecular event that has profound impact on prognosis. The greater the number of copies, the worse is the prognosis. MYCN amplification is currently the most important genetic abnormality used in risk stratification of neuroblastic tumors. 

About 90% of neuroblastomas produce catecholamines (as pheochromocytomas), which are an important diagnostic feature (i.e., elevated blood levels of catecholamines and elevated urine levels of catecholamine metabolites such as vanillylmandelic acid [VMA] and homovanillic acid [HVA]). 

NECROSIS

Definition: Necrosis is defined as the morphologic changes caused by the progressive degradative
action of enzymes on the lethally injured cell.

These changes are due to
I. Autolysis and
2. Heterolysis.

The cellular changes of necrosis i.e. death of circumscribed group of cells in continuity with living tissues are similar to changes in tissues following somatic death, except that in the former, there is leucocytic infiltration in reaction to the dead cells and the lytic
enzymes partly come from the inflammatory cell also. (Heterolysis). Cell death occurs in the normal situation of cell turnover also and this is called apoptosis-single cellular dropout.

Nuclear changes in necrosis

As cytoplasmic changes are a feature of degeneration ,similarly nuclear changes are the hallmark of necrosis. These changes are:
(i) Pyknosis –condensation of chromatin
(ii) Karyorrhexis - fragmentation
(iii) Karyolysis - dissolution

Types of necrosis

(1) Coagulative necrosis: Seen in infarcts. The architectural outlines are maintained though structural details are lost. E.g, myocardial infarct.
(2) Caseous necrosis: A variant of coagulative necrosis seen in tuberculosis. The architecture is destroyed, resulting in an  eosinophilic amorphous debris.
(3) Colliquative (liquifactive). Necrosis seen in Cerebral infarcts and suppurative necrosis.

Gangrenous necrosis: It is the necrosis with superadded putrefaction

May be:
a. dry - coagulative product.
b. Wet - when there is bacterial liquifaction.

Fat necrosis

May be:
a. Traumatic (as in breast and subcutaneous tissue).
b Enzymatic (as in pancreatitis). It shows inflammation of fat with formation of lipophages and giant cells.

This is often followed by deposition of calcium as calcium soaps.

Hyaline necrosis: Seen in skeletal muscles in typhoid and in liver ceIs in some forms of hepatitis.

Fibrinoid necrosis: In hypertension and in immune based diseases.
 

Chronic hepatitis

Chronic hepatitis occurs in 5%-10% of HBV infections and in well over 50% of HCV; it does not occur in HAV. Most chronic disease is due to chronic persistent hepatitis. The chronic form  is more likely to occur in the very old or very young, in males, in immunocompromised hosts, in Down's syndrome, and in dialysis patients.

a. Chronic persistent hepatitis is a benign, self-limited disease with a prolonged recovery. Patients are asymptomatic except for elevated transaminases. 

b. Chronic active hepatitis features chronic inflammation with hepatocyte destruction, resulting in cirrhosis and liver failure. 
(1) Etiology. HBV, HCV, HDV, drug toxicity, Wilson's disease, alcohol, a,-antitrypsin deficiency, and autoimmune  hepatitis are common etiologies.
(2) Clinical features may include fatigue, fever, malaise, anorexia, and elevated liver function tests. 
(3) Diagnosis is made by liver biopsy.

8. Carrier state for HBV and HCV may be either asymptomatic or with liver disease; in the latter case, the patient has elevate transaminases.
a. Incidence is most common in immunodeficient, drug addicted, Down's syndrome, and dialysis patients. 
b. Pathology of asymptomatic carriers shows "ground-glass"" hepatocytes with finely granular eosinophilic cytoplasm.