Cryptococcosis

An infection acquired by inhalation of soil contaminated with the encapsulated yeast Cryptococcus neoformans, which may cause a self-limited pulmonary infection or disseminate, especially to the meninges, but sometimes to the skin, bones, viscera, or other sites.

Cryptococcosis is a defining opportunistic infection for AIDS, although patients with Hodgkin's or other lymphomas or sarcoidosis or those receiving long-term corticosteroid therapy are also at increased risk.

AIDS-associated cryptococcal infection may present with severe, progressive pneumonia with acute dyspnea and an x-ray pattern suggestive of Pneumocystis infection.

Primary lesions in the lungs are usually asymptomatic and self-limited

Pneumonia usually causes cough and other nonspecific respiratory symptoms. Rarely, pyelonephritis occurs with renal papillary necrosis development.

Most symptoms of cryptococcal meningitis are attributable to brain swelling and are usually nonspecific, including headache, blurred vision, confusion, depression, agitation, or other behavioral changes. Except for ocular or facial palsies, focal signs are rare until relatively late in the course of infections. Blindness may develop due to brain swelling or direct involvement of the optic tracts. Fever is usually low-grade and frequently absent.

Rickets and Osteomalacia 

Rickets in growing children and osteomalacia in adults are skeletal diseases with worldwide distribution. They may result from
1. Diets deficient in calcium and vitamin D
2. Limited exposure to sunlight (in heavily veiled women, and inhabitants of northern climates with scant sunlight)
3. Renal disorders causing decreased synthesis of 1,25 (OH)2-D or phosphate depletion 
4. Malabsorption disorders.

Although rickets and osteomalacia rarely occur outside high-risk groups, milder forms of vitamin D deficiency (also called vitamin D insufficiency) leading to bone loss and hip fractures are quite common in the elderly.

Whatever the basis, a deficiency of vitamin D tends to cause hypocalcemia. When hypocalcemia occurs, PTH production is increased, that ultimately leads to restoration of the serum level of calcium to near normal levels (through mobilization of Ca from bone & decrease in its tubular reabsorption) with persistent hypophosphatemia (through increase renal exretion of phosphate); so mineralization of bone is impaired or there is high bone turnover.

The basic derangement in both rickets and osteomalacia is an excess of unmineralized matrix. This complicated in rickets by derangement of endochondral bone growth.

The following sequence ensues in rickets:
1. Overgrowth of epiphyseal cartilage with distorted, irregular masses of cartilage
2. Deposition of osteoid matrix on inadequately mineralized cartilage
3. Disruption of the orderly replacement of cartilage by osteoid matrix, with enlargement and lateral expansion of the osteochondral junction
4. Microfractures and stresses of the inadequately mineralized, weak, poorly formed bone
5. Deformation of the skeleton due to the loss of structural rigidity of the developing bones 

Gross features
• The gross skeletal changes depend on the severity of the disease; its duration, & the stresses to which individual bones are subjected.
• During the nonambulatory stage of infancy, the head and chest sustain the greatest stresses. The softened occipital bones may become flattened. An excess of osteoid produces frontal bossing. Deformation of the chest results from overgrowth of cartilage or osteoid tissue at the costochondral junction, producing the "rachitic rosary." The weakened metaphyseal areas of the ribs are subject to the pull of the respiratory muscles and thus bend inward, creating anterior protrusion of the sternum (pigeon breast deformity). The pelvis may become deformed.
• When an ambulating child develops rickets, deformities are likely to affect the spine, pelvis, and long bones (e.g., tibia), causing, most notably, lumbar lordosis and bowing of the legs .
• In adults the lack of vitamin D deranges the normal bone remodeling that occurs throughout life. The newly formed osteoid matrix laid down by osteoblasts is inadequately mineralized, thus producing the excess of persistent osteoid that is characteristic of osteomalacia. Although the contours of the bone are not affected, the bone is weak and vulnerable to gross fractures or microfractures, which are most likely to affect vertebral bodies and femoral necks.

Microscopic features

• The unmineralized osteoid can be visualized as a thickened layer of matrix (which stains pink in hematoxylin and eosin preparations) arranged about the more basophilic, normally mineralized trabeculae.

Neutrophilia
Causes
    
-Pyogenic infections.
-Haemorrhage and trauma.
-Malignancies.
-Infarction.
-Myelo proliferative disorders.

Staphylococcal Infection

Staphylococci, including pathogenic strains, are normal inhabitants of the nose and skin of most healthy people
Virulence factors include coagulase (which clots blood), hemolysin, and protein A (which ties up Fc portions of antibodies). Although we have antibodies against staphylococci, they are of limited usefulness. 

Staphylococci (and certain other microbes) also produce catalase, which breaks down H2O2, rendering phagocytes relatively helpless against them. 

The coagulase-positive staphylococcus (Staphylococcus pyogenes var. aureus) is a potent pathogen. It tends to produce localized infection
It is the chief cause of bacterial skin abscesses. Infection spreads from a single infected hair (folliculitis) or splinter to involve the surrounding skin and subcutaneous tissues

Furuncles are single pimples
carbuncles are pimple clusters linked by tracks of tissue necrosis which involve the fascia.

Impetigo is a pediatric infection limited to the stratum corneum of the skin -- look for honey-colored crusts

Staphylococcal infections of the nail-bed (paronychia) and palmar fingertips (felons) are especially painful and destructive

These staph are common causes of wound infections (including surgical wounds) and of a severe, necrotizing pneumonia. Both are serious infections in the hospitalized patient.

Staph is the most common cause of synthetic vascular graft infections. Certain sticky strains grow as a biofilm on the grafts

Staph aureus is pathogenic, β-hemolytic, and makes coagulase.
Staph epidermidis are non-pathogenic strains that don’t make coagulase.  Often Antibiotics resistant, and     can become opportunistic infections in hospitals.

Staph aureus is normal flora in the nose and on skin, but can also colonize moist areas such as perineum.  Causes the minor infections after cuts.  Major infections occur with lacerations or immune compromise, where large number of cocci are introduced.

While Staph aureus can invade the gut directly (invasive staphylococcal enterocolitis), it is much more common to encounter food poisoning due to strains which have produced enterotoxin B, a pre-formed toxin in un-refrigerated meat or milk products

Staph epidermidis (Coagulase-negative staphylococci)
Universal normal flora but few virulence factors.  Often antibiotic resistant.
Major cause of foreign body infections such as prosthetic valve endocarditis and IV line sepsis.

Staph saprophyticus
Common cause of UTI in women.

Pathogenicity
Dominant features of S. aureus infections are pus, necrosis, scarring.  The infections are patchy.  Serious disease is rare because we are generally immune.  However, foreign bodies or necrotic tissue can start an infection.  Staph infections include wound infections, foreign body sepsis, pneumonia, meningitis.
Occassionally, S. aureus can persist within cells.

Major disease presentations include:
    --Endocarditis
    --Abscesses (due to coagulase activity)
    --Toxic Shock
    --Wound infections
    --Nosocomial pneumonia

Prevention of Staph aureus infections
S. aureus only lives on people, so touching is the main mode of transmission.  Infected patients     should be isolated, but containment is easy with intense hand washing.
 

Eosinopenia:
Causes

-Corticoid effect (Cushing's syndrome or therapy).
-Stress.

Sickle Cell Disease

Sickle cell anemia is a autosomal recessive genetic disorder. It affects the BETA GLOBIN gene on the CHROMOSOME 16. In sickle cell anemia, the hemoglobin abnormality consists of a point mutation in the beta chain gene for hemoglobin; the resulting abnormal gene product is denoted HbS. If you are heterozygous for the HbS gene you will have what is called sickle trait, which is asymptomatic .

 If you are homozygous for the HbS gene  you will get sickle cell disease, which is symptomatic in most patients.
 The problem with HbS is that as it releases oxygen, it polymerizes and aggregates with other HbS molecules, making the red cell stiff and distorted. These distorted, sickle-shaped red cells are fragile so the patient can end up with a hemolytic anemia.
This can occur as pure disease (homozygous) or trait (heterozygous) or with other haemoglobinopathies. It is common. in Negroes. It is due to Hb-s  which is much less soluble than Hb-A  hence deoxygenation insoluble form  sickling of RBC.

This causes:
•    Removal by RE system. 
•    Blockage of microvessels causing  ischaemia.