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.

Parasitic
1. Leishmania produce 3 kinds of disease in man

- visceral leishmaniasis (kala azar) due to Leishmania donovani complex, 
- cutaneous leishmaniasis due to Leishmania tropica complex, and 
- mucocutaneous leishmaniasis due to Leishmania braziliensis. 
 
 - cutaneous (Oriental sore) and mucocutansous leishmaniasis limit themselves to the skinalone (ulcers) in the former disease and skin plus mucous membranes in the latter variant. 

 - the diagnosis of cutaneous or mucocutaneous leishmaniasis is made by biopsy, culture, skin test, or serologic tests
 
 - the laboratory diagnosis of visceral leishmaniasis is made by performing a bone marrow aspirate and finding the leishmanial forms in macrophages, by culture, by hamster inoculation, or by serology. 
 - recovery from the cutaneous form incurs immunity.
 - treatment: stibogluconate 

IMMUNITY AND RESISTANCE TO INFECTION

Body's resistance to infection depends upon:

I. Defence mechanisms at surfaces and portals of entry.

II. Nonspecific or innate immunity

Ill. Specific immune response.

Achrondroplasia 
is a major cause of dwarfism. The underlying etiology is a point mutation in the fibroblast growth factor receptor, which causes inhibition of chondrocyte proliferation, which is associated with suppression of the normal epiphyseal growth plate expansion. Thus, long bone growth is markedly shortened.
The most conspicuous changes include disproportionate shortening of the proximal extremities, bowing of the legs, and a lordotic posture. 

Microscopically, the cartilage growth plates are disorganized and hypoplastic. 

AMYLOIDOSIS

Definition. Extra cellular  deposition of an eosinophilic hyaline homogenous material in Various organs, occurring in a variety of clinical  states.

Staining reactions

Iodine :- Brown, turning blue on addition of H2SO4 (gross and microscopic Stain).
P.A.S. – Positive  (Magenta pink).
Congo Red -Orange red which on polarisation gives green birefringence.
Von Geison's –Khaki colour.
Thioflavin T -Yellow fluorescence.

Amyloid is called typical if it given the above staining  reactions Other wise it is termed atypical or para-amyloid.

Classification 

1.    Systemic  amyloidosis associated with underlying disease (secondary),

(A) Chronic infections like 

- Tuberculosis.
- Bronchiectasis.
- Lung abscess.
- Osteomyelitis.
- Syphilis.

(B) Chronic inflammations of varied etiology:

- Rheumatoid arthritis.
- Ulcerative colitis.
- Regional enteritis.
- Lupus erythematosus.

(C) Neoplastic proliferations:

- Of immune system – Multiple myeloma, Hodgkin’s disease.
- Cancers like Renal cell carcinoma etc.

II Systemic primary amyloidosis  with no underlying cause.

III Heredofamilial types.

- Amyloidosis with mediterranean fever.
- Amyloid polyneuropathy.
- Amyloid nephrophathy
- Familial cardiac amyloidosis
- Familial cutaneous amyloid.
- Lattice corneal dystrophy

IV. Localised amyloidosis:

- Senile - in heart, brain, seminal vesicles.
- Amyloidoma of tongue, bronchial tree, skin.
- In islets of Langerhans in Diabetes mellitus.
- In medullary thyroid carcinoma.

Deposition sites
In relation to reticulin  and collagen fibres and to basement, membranes especially
subendothelial. 

Organs involved commonly are : 

Secondary amyloidosis

- Liver.
- Spleen.
- Kidney
- Lymph nodes.
- Adrenals.

Primary amyloidosis

- Heart
- Tongue and gingiva.
- Gastro intestinal tract.
- Lung.
- Wall of small vessels.

Nature and pathogenesis of amyloid
It is primarily made up of protein arranged in two patterns

- There are filaments twisted together to from the fibrils. These chemically resemble light chains of immunoglobulins
- Rods composed of stacked rings. These are made up of alpha globulin components of plasma proteins (P-components)

- In addition to these, extracts of crude amyloid contain  mucopolysacharides complement and gamma globulins.

- Origin of amyloid :- current concept is that it is a direct product of cells of the immune sustem with some abnormality in their immune response

The abnormality may be due to :
- A genetic enzyme defect.
- Prolonged antigenic challenge.
- Neoplastic transformation
- Supression of normal. Response as in induced tolerance.

Posterior Pituitary Syndromes 

The posterior pituitary, or neurohypophysis, is composed of modified glial cells (termed pituicytes) and axonal processes extending from nerve cell bodies in the hypothalamus. The hypothalamic neurons produce two peptides: antidiuretic hormone (ADH) and oxytocin that are stored in axon terminals in the neurohypophysis.

The clinically important posterior pituitary syndromes involve ADH production and include  
1. Diabetes insipidus and 
2. Inappropriate secretion of high levels of ADH.  

- ADH is released into the general circulation in response to increased plasma oncotic pressure & left atrial distention. 
- It acts on the renal collecting tubules to increase the resorption of free water. 
- ADH deficiency causes  diabetes insipidus, a condition characterized by polyuria. If the cause is related to ADH Diabetes insipidus from - - ADH deficiency is designated as central, to differentiate it from nephrogenic diabetes insipidus due to renal tubular unresponsiveness to circulating ADH. 
- The clinical manifestations of both diseases are similar and include the excretion of large volumes of dilute urine with low specific gravity. Serum sodium and osmolality are increased as a result of excessive renal loss of free water, resulting in thirst and polydipsia. 

- ADH excess causes resorption of excessive amounts of free water, with resultant hyponatremia. 
- The most common causes of the syndrome include the secretion of ectopic ADH by malignant neoplasms (particularly small-cell carcinomas of the lung), and local injury to the hypothalamus and/or neurohypophysis. 

- The clinical manifestations are dominated by hyponatremia, cerebral edema, and resultant neurologic dysfunction.