Systemic Candidiasis (Candidosis; Moniliasis)

Invasive infections caused by Candida sp, most often C. albicans, manifested by fungemia, endocarditis, meningitis, and/or focal lesions in liver, spleen, kidneys, bone, skin, and subcutaneous or other tissues.

Infections due to Candida sp account for about 80% of all major systemic fungal infections.

Symptoms and Signs

Esophagitis is most often manifested by dysphagia. Symptoms of respiratory tract infections are nonspecific, such as cough. Vaginal infections cause itching, burning, and discharge. Candidemia usually causes fever, but other symptoms are typically nonspecific. Sometimes, a syndrome develops resembling bacterial sepsis, with a fulminating course that may include shock, oliguria, renal shutdown, and disseminated intravascular coagulation.

Hematogenous endophthalmitis starts as white retinal plaques that can cause blindness as destructive inflammation progresses, extending to opacify the vitreous and causing potentially irreversible scarring. Most often, there are no symptoms in early stages of Candida endophthalmitis. If treatment is not begun before symptoms appear, significant or even total loss of vision is likely to occur in the affected eye. In neutropenic patients, eye involvement is more often manifested by retinal hemorrhages; papulonodular, erythematous, and vasculitic skin lesions may also develop.

Multiple Endocrine Neoplasia Syndromes (MEN)

The MEN syndromes are a group of inherited diseases resulting in proliferative lesions (hyperplasias, adenomas, and carcinomas) of multiple endocrine organs. Even in one organ, the tumors are often multifocal. These tumors are usually more aggressive and recur in a higher proportion of cases than similar but sporadic endocrine tumors. 

Multiple Endocrine Neoplasia Type 1 (MEN1) is inherited in an autosomal dominant pattern. The gene (MEN1) is a tumor suppressor gene; thus, inactivation of both alleles of the gene is believed to be the basis of tumorigenesis. Organs commonly involved include the parathyroid, pancreas, and pituitary (the 3 Ps). Parathyroid hyperplasia is the most consistent feature of MEN-1 but endocrine tumors of the pancreas are the leading cause of death because such tumors are usually aggressive and present with metastatic disease.

Zollinger-Ellison syndrome, associated with gastrinomas, and hypoglycemia, related to insulinomas, are common endocrine manifestations. Prolactin-secreting macroadenoma is the most frequent pituitary tumor in MEN-1 patients. 

Multiple Endocrine Neoplasia Type 2 (MEN2)

MEN type 2 is actually two distinct groups of disorders that are unified by the occurrence of activating mutations of the RET protooncogene. Both are inherited in an autosomal dominant pattern. 

MEN 2A

Organs commonly involved include:

Medullary carcinoma of the thyroid develops in virtually all cases, and the tumors usually occur in the first 2 decades of life. The tumors are commonly multifocal, and foci of C-cell hyperplasia can be found in the adjacent thyroid. Adrenal pheochromocytomas develop in 50% of patients; fortunately, no more than 10% are malignant. Parathyroid gland hyperplasia with primary hyperparathyroidism occurs in a third of patients. 

Multiple Endocrine Neoplasia, Type 2B 

Organs commonly involved include the thyroid and adrenal medulla. The spectrum of thyroid and adrenal medullary disease is similar to that in MEN-2A. However, unlike MEN-2A, patients with MEN-2B: 

1. Do not develop primary hyperparathyroidism
2. Develop extraendocrine manifestations: ganglioneuromas of mucosal sites (gastrointestinal tract, lips, tongue) and marfanoid habitus 

Bacterial endocarditis 
Endocarditis is an infection of the endocardium of the heart, most often affecting the heart valves.

A. Acute endocarditis
1. Most commonly caused by Staphylococcus aureus.
2. It occurs most frequently in intravenous drug users, where it usually affects the tricuspid valve. 

B. Subacute endocarditis

1. Most commonly caused by less virulent organisms, such as intraoral Streptococcus viridans that can be introduced systemically via dental procedures.
2. Pathogenesis: occurs when a thrombus or vegetation forms on a previously damaged or congenitally abnormal valve. These vegetations contain bacteria and inflammatory cells. Complications can arise if the thrombus embolizes, causing septic infarcts.
Other complications include valvular dysfunction or abscess formation.
3. Symptoms can remain hidden for months.
4. Valves affected (listed most to least common):
a. Mitral valve (most frequent).
b. Aortic valve.
c. Tricuspid (except in IV drug users, where the tricuspid valve is most often affected).

G-6 PD Deficiency

Occurs in Negroes, Mediterranean races, India and far East. It confers a protection Against falciparum malaria.

It is transmitted as X-linked trait of intermediate dominance (variable effect in homozygous females). 

Haemolysis may be induced by :
•    Primaquin and other anti malarials.
•    Other drugs like chloramphenicol , analgesics, antitubercular drugs etc.
•    Infections.
•    Ingestion of Vicia faba bean (favism).
•    Diabetic acidosis
 

Acute leukaemia
Lympheblastic is commoner in children and myeloblastic in adults .

Features:
- Anaemia.
- Fever and infections especially oral and respiratory.
- Haemorrhagic tendencies.
- Bone pains and tenderness (sternal).
- Lymphnode enlargement especially in lymphocytic.
- Gum hypertrophy especially in monocytic.

Blood picture:

- Anaemia and thrombocytopenia.
- Leucocyte count usually 20,-50,000/cu.mm. It may be less in subleukaemic leukaemia (even leucopenic levels may be seen).
- Blast cells form 30-90% of cells. Smudge cells and basket cells are seen .The type of balst cell may be recognised  by the associated more mature forms or by special cytochemical stains
- Blasts may be few in peripheral blood in the aleukamic stage

 Bone Marrow

- May be a dry tap , necessitating a trephine biopsy 
- Hypercellular with 70-90% blasts
- Reduction in megakaryocytes and erythroid cells
 

Pathology gives explanations of a disease by studying the following four aspects of the disease.

1. Etiology,

2. Pathogenesis,

3. Morphologic changes and

4. Functional derangements and clinical significance.

1. Etiology Etiology of a disease means the cause of the disease. If the cause of a disease is known it is called primary etiology. If the cause of the disease is unknown it is called idiopathic. Knowledge or discovery of the primary cause remains the backbone on which a diagnosis can be made, a disease understood, & a treatment developed. There are two major classes of etiologic factors: genetic and acquired (infectious, nutritional, chemical, physical, etc).

2. Pathogenesis Pathogenesis means the mechanism through which the cause operates to produce the pathological and clinical manifestations. The pathogenetic mechanisms could take place in the latent or incubation period. Pathogenesis leads to morphologic changes.

3. Morphologic changes The morphologic changes refer to the structural alterations in cells or tissues that occur following the pathogenetic mechanisms. The structural changes in the organ can be seen with the naked eye or they may only be seen under the microscope. Those changes that can be seen with the naked eye are called gross morphologic changes & those that are seen under the microscope are called microscopic changes. the morphologic changes will lead to functional alteration & to the clinical signs & symptoms of the disease.

4. Functional derangements and clinical significance The morphologic changes in the organ influence the normal function of the organ. By doing so, they determine the clinical features (symptoms and signs), course, and prognosis of the disease.