Infections caused by N. meningiditis

1.  Bacteremia without sepsis.  Organism spreads to blood but no major reaction.

2.  Meningococcemia without meningitis.  Fever, headache, petechia, hypotension, disseminated       intravascular coagulation.  The Waterhouse-Friderichsen Syndrome is a rapid, progressive meningococcemia with shock, organ failure, adrenal necrosis, and death.

3.  Meningitis with meningococcemia.  Sudden onset fever, chills, headache, confusion, nuchal rigidity.  This occurs rapidly.

4.  Meningoencephalitis.  Patients are deeply comatose.

Diagnosis made by examining CSF.

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.  
 

Leukaemias
Uncontrolled proliferation of leukocyte precursors (may be with associated red cell and platelet series proliferation).

Factors which may playa causal role are.
- Viral
- Radiation.
- Genetic.

Classification

1. Acule leukaemia:

a. Lymphocytic (lymphoblastic).
b. Myelocytic and promyelocytic (myeloblastic).
c. Monocytic.
d. Myelomonocytic.
e. Undifferentiated (Stem cell).

2. Chronic leukaemia:

a. Lymphocytic
b. Myelocytic

3. Miscellaneous:
a. Erythroleukaemia (De Guglielmo's disease).
b. Eosinophilic leukaemia.
c. Megakaryocytic leukaemia.

Infectious Mononucleosis

It is an Epstein Barr virus infection in children and young adults.

Features

-Constitutional symptoms.
-Sore throat.
-Lymphnode enlargement.
-Skin rashes
-Jaundice.
-Rarely pneumonia, meningitis and encephalitis.

Blood Picture

- Total count of I0,000. 20,000 /cu.mm.
- Lymphocytosis (50-90%) with atypical forms. They are larger with more cytoplasm which may be vacuolated or basophilic. Nucleus may be indented. with nucleoli (Downy type I to III).
- Platelets may be reduced.
- Paul Bunell test (for heterophil antibody against sheep RBC) is positive
 

Streptococcal pharyngitis:

A disease of young people, enlarged lymphoid nodules and keratin plugs in the tonsillar pits is seen Complications include retro-pharyngeal abscess (quinsy)

Cellulitis of the deep tissues of the neck is Ludwig's angina

Scarlet fever ("scarlatina") is a strep throat caused by a streptococcus with the gene to make one of the erythrogenic toxins, Patients have a rash with PMNs

Streptococcal skin infections (Impetigo)

Erysipelas is a severe skin infection caused by group A strep; geographic of red, thickened, indurated areas of the skin are characteristic. Unlike staph infections, there is usually little or no tissue necrosis

Post-streptococcal hypersensitivity diseases include rheumatic fever, post-streptococcal glomerulonephritis, and some cases of erythema nodosum

A dermatofibroma is a benign tumor of the dermis, MC located on the lower extremity, where it has a nodular, pigmented appearance.
 - composed of benign histiocytes.