Viral meningitis
1. Can be caused by many different viruses, including cytomegalovirus, herpes virus, rabies, and HIV.
2. CSF fluid from a spinal tap differs from that seen in a bacterial infection. It shows mononuclear cells, higher levels of protein, and normal levels of glucose.

CHRONIC INFLAMMATlON

When the inflammatory reaction instead of subsiding after the acute phase (or without entering an acute phase), persists as a smouldering lesion, it is called chronic inflammation. .

Characteristics

• Predominantly mononuclear response.
• Inflamation.and..repair going on simultaneously.
• Usually results in more prominent-scarring.

Causes:

Chronicity may be due to :

- Defective defence mechanisms.

- Persistence of injurious agent.

(a) Certain organisms resist phagocytosis and destruction e.g tubercle bacillus, fungi

(b) insoluble particulate matter e.g., crystals. fibres suture materials.

(c) Constants supply of causative agent as in autoimmune disease where body reacts against its own tissues.

- Defective healing.

Granulomatous inflammation

It is a type of chronic inflammation characterised by localised collections of histiocytes.

These cells are usually accompanied by lymphocytes, fibroblasts and giant cells also.

Granulomas are characteristically seen in diseases like tuberculosis. syphilis, leprosy, sarcoidosis, fungal infections etc. In some of these, the lesion is morphologically distinct  enough to point to the type of underlying disease. These are sometimes called' specific' granulomas. Granulomas can also be elicited by particulate, insoluble foreign material e.g. granuloma, suture granuloma, cholesterol granuloma (organising haemorrhages).

ADRENOCORTICAL TUMORS

Functional adenomas are commonly associated with hyperaldosteronism and with Cushing syndrome, whereas a virilizing neoplasm is more likely to be a carcinoma. Determination of of the functional status of a tumor is based on clinical evaluation and measurement of the hormone or its metabolites. In other words, functional and nonfunctional adrenocortical neoplasms cannot be distinguished on the basis of morphologic features. 

Patholgical features
Adrenocortical adenomas

- They are generally small, 1 to 2 cm in diameter. 
- On cut surface, adenomas are usually yellow to yellow-brown due to presence of lipid within the neoplastic cells 
- Microscopically, adenomas are composed of cells similar to those populating the normal adrenal cortex. The nuclei tend to be small, although some degree of pleomorphism may be encountered even in benign lesions ("endocrine atypia"). The cytoplasm ranges from eosinophilic to vacuolated, depending on their lipid content. 

Adrenocortical carcinomas 

These are rare and may occur at any age, including in childhood.  
- Carcinomas are generally large, invasive lesions. 
- The cut surface is typically variegated and poorly demarcated with areas of necrosis, hemorrhage, and cystic change.
- Microscopically, they are composed of well-differentiated cells resembling those of cortical adenomas or bizarre, pleomorphic cells, which may be difficult to distinguish from those of an undifferentiated carcinoma metastatic to the adrenal.  

Anemia (Disorder of Hematopoietic System) - Probably the most common effect of nutritional deficiency. Any factor that decreases hematopoiesis can cause an anemia.

A. Iron deficiency - Widely recognized as the most important cause of anemia, It is indicated that ½ of all pregnant women and infants are affected, as are ~13% of all adult women.

1. Dietary factors - Availability of iron from different food sources and mixtures.
2. Malabsorption – One third of patients with inflammatory bowel disease (IBD) have recurrent anemia and 30% or more of patients who have had partial gastrectomy will develop iron deficiency anemia.
3. Blood loss - Menses, gastrointestinal bleeding 
4. Increased demand - Pregnancy, growth in children.
5. Congenital - Atransferrinemia
6. Importance of multiple factors.
7. Pathophysiology - Initially iron is mobilized from reticuloendothelial stores and increased intestinal absorption occurs. Total iron stores are depleted, serum iron levels fall. In severe cases in peripheral blood, the red cells become smaller (microcytic) and their hemoglobin content is reduced (hypochromic).  

B. Megaloblastic anemias- Characterized by the presence of abnormal WBCs and RBCs. In severe cases, megaloblasts (abnormal red cell precursors) may be present. These anemias are a consequence of disordered DNA synthesis.
1. Folate deficiency - Can be caused by:
a. Dietary deficiency
b. Malabsorption (celiac disease)
c. Increased demand (pregnancy & lactation)
d. Drugs - methotrexate, anticonvulsants, oral contraceptives, alcoholism.
e. Liver disease

2. Cobalamin (vitamin B12) deficiency - Almost always a secondary disorder that can  be caused by:

a. Intrinsic factor deficiency (pernicious anemia due to autoimmune destruction of the gastric mucosa)

b. Malabsorption

3. Pyridoxine (vitamin B6) deficiency- most commonly associated with alcoholism.

C. Other factors known to be frequently associated with anemia would include protein-calorie malnutrition, vitamin C deficiency, and pyridoxine deficiency (usually associated with alcoholism).

D. Other anemias not particularly associated with nutritional disease would include hemolytic anemia
(decreased red cell life span) and aplastic anemia (failure of marrow to produce new cells).  

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.

HAEMORRHAGIC DISORDERS

Normal homeostasis depends on

 -Capillary integrity and tissue support.

- Platelets; number and function

(a) For integrity of capillary endothelium and platelet plug by adhesion and aggregation

(b) Vasoactive substances for vasoconstriction

(c) Platelet factor for coagulation.

(d) clot retraction.

- Fibrinolytic system(mainly Plasmin) : which keeps the coagulatian system in check.

Coagulation disorders

These may be factors :

Deficiency .of factors

• Genetic.
• Vitamin K deficiency.
• Liver disease.
• Secondary to disseminated intravascular coagulation.or defibrinatian

Overactive fibrinolytic system.

Inhibitors of  the factars (immune, acquired).

Anticoagulant therapy as in myocardial infarctian.

Haemophilia. Genetic disease transmitted as X linked recessive trait. Comman in Europe. Defect in fcatorVII  Haemophilia A .or in fact .or IX-Haemaphilia B (rarer).

Features:

• May manifest in infancy or later.
• Severity depends  on degree of deficiency.
• Persistant woundbleeding.
• Easy Bruising with Haemotoma formation

Nose bleed , arthrosis, abdominal pain with fever and leucocytosis

Prognosis is good with prevention of trauma and-transfusion of Fresh blood or fTesh plasma except for danger of developing immune inhibitors.

Von Willebrand's disease. Capillary fragility and decreased factor VIII (due to deficient stimulatory factor). It is transmitted in an autosomal dominant manner both. Sexes affected equally

Vitamin K  Deficiency. Vitamin K is needed for synthesis of factor II,VII,IX and X.

Deficiency maybe due to:

Obstructive jaundice.

Steatorrhoea.

Gut sterilisation by antibiotics.

Liver disease results in :

Deficient synthesis of factor I II, V, Vll, IX and X  Incseased fibrinolysis (as liver is the site of detoxification of activators ).

Defibrination syndrome. occurs when factors are depleted due to disseminated .intravascular coagulation (DIC). It is initiated by endothelial damage or tissue factor entering the circulation.

Causes

Obstetric accidents, especially amniotic fluid embolism. Septicaemia. .

Hypersensitivity reactions.

Disseminated malignancy.

Snake bite.

Vascular defects :

(Non thrombocytopenic purpura).

Acquired :

Simple purpura a seen in women. It is probably endocrinal

Senile parpura in old people due to reduced tissue support to vessels

Allergic or toxic damage to endothelium due to  Infections like Typhoid Septicemia

Col!agen diseases.

Scurvy

Uraemia damage to  endothelium (platelet defects).

Drugs like aspirin. tranquillisers, Streptomvcin pencillin etc.

Henoc schonlien purpura Widespeard vasculitis due to hypersensitivity to bacteria or foodstuff

It manifests as :

Pulrpurric rashes.

Arthralgia.

Abdominal pain.

Nephritis and haematuria.

Hereditary :

(a) Haemhoragic telangieclasia. Spider like tortous vessels which bleed easily. There are disseminated lesions in skin, mucosa and viscera.

(b) Hereditary capillary fragilily similar to the vascular component of von Willbrand’s disease

.(c) Ehler Danlos Syndrome which is a connective tissue defect with skin, vascular and joint manifestations.

Platelet defects

These may be :

(I) Qualitative thromboasthenia and thrombocytopathy.

(2) Thrombocytopenia :Reduction in number.

(a) Primary or idiopathic thrombocytopenic purpura.

(b) Secondary to :

(i) Drugs especially sedormid

(ii) Leukaemias

(iii) Aplastic-anaemia.

Idiopathic thrombocytopenic purpura (ITP). Commoner in young females.

Manifests as :

Acute self limiting type.

Chronic recurring type.

Features:

(i) Spontaneous bleeding and easy bruisability

(ii)Skin (petechiae), mucus membrane (epistaxis) lesions and sometimes visceral lesions involving any organ.

Thrombocytopenia with abnormal forms of platelets.

Marrow shows increased megakaryocytes with immature forms,

vacuolation, and lack of platelet budding.

Pathogenesis:

hypersensitivity to infective agent in acute type.

Plasma thrombocytopenic factor ( Antibody in nature) in chronic type