Connective tissue diseases
Marfan’s syndrome
a. Genetic transmission: autosomal dominant.
b. Characterized by a defective microfibril glycoprotein, fibrillin.
c. Clinical findings include tall stature, joints that can be hyperextended, and cardiovascular defects, including mitral valve prolapse and dilation of the ascending aorta.

Ehlers-Danlos syndrome
a. Genetic transmission: autosomal dominant or recessive.
b. This group of diseases is characterized by defects in collagen.
c. Clinical findings include hypermobile joints and highly stretchable skin. The skin also bruises easily. Oral findings include Gorlin’s sign and possible temporomandibular joint (TMJ) subluxation. 
The oral mucosa may also appear more fragile and vulnerable to trauma. 

Nevus

A nevus refers to any congenital lesion of the skin, while a nevocellular nevus specifically refers to a benign tumor of neural crest-derived cells that include modified melanocytes of various shapes (nevus cells).
 - nevocellular nevi are generally tan to deep brown, uniformly pigmented, small papules with well-defined, rounded borders.
 - most nevocellular nevi are subdivided into junctional, intradermal, or compound types.
 - most nevocellular nevi begin as junctional nevi with nevus cells located along the basal cell layer producing small, flat lesions, which are only slightly raised. 
- junctional nevi usually develop into compound nevi as nevus cells extend into the underlying superficial dermis forming cords and columns of cells (compound: nevi at junction and in the dermis).
 - eventually, the junctional component of a nevocellular nevus is lost, leaving only nevus cells within the dermis, thus the term intradermal nevus.
 - junctional → compound → intradermal nevus.
 - although uncommon, certain nevi may evolve into a malignant melanoma, particularly those which are congenital and those which are referred to as dysplastic nevi.
 - a dysplastic nevus is commonly associated with patients who have multiple scattered nevi over the entire body (dysplastic nevus syndrome) with individual lesions that have a diameter greater than 1 cm.

Pleural effusion is a medical condition where fluid accumulates in the pleural cavity which surrounds the lungs, making it hard to breathe.

Four main types of fluids can accumulate in the pleural space:

Serous fluid (hydrothorax)

Blood (hemothorax)

Lipid (chylothorax)

Pus (pyothorax or empyema)

Causes:

Pleural effusion can result from reasons such as:

• Cancer, including lung cancer or breast cancer
• Infection such as pneumonia or tuberculosis
• Autoimmune disease such as lupus erythematosus
• Heart failure
• Bleeding, often due to chest trauma (hemothorax)
• Low oncotic pressure of the blood plasma
• lymphatic obstruction
• Accidental infusion of fluids

Congestive heart failure, bacterial pneumonia and lung cancer constitute the vast majority of causes in the developed countries, although tuberculosis is a common cause in the developing world.

Diagnosis:

1. Gram stain and culture - identifies bacterial infections
2. Cell count and differential - differentiates exudative from transudative effusions
3. Cytology - identifies cancer cells, may also identify some infective organisms
4. Chemical composition including protein, lactate dehydrogenase, amylase, pH and glucose - differentiates exudative from transudative effusions
5. Other tests as suggested by the clinical situation - lipids, fungal culture, viral culture, specific immunoglobulins

Avitaminoses -  Vitamin deficiencies are more commonly secondary disorders associated with malabsorption conditions and chronic alcoholism.

A. Vitamin A - (retinoids, fat soluble compounds derived from ß-carotene) The best-known effect of deficiency is an inability to see in weak light (night blindness due to decreased rhodopsin).
-> The pathology is also characterized by skin lesions (rash on the extremities with punctate erythematous lesions). In malnourished children, vitamin A supplements reduce the incidence of infections such as measles, even in children without signs of preexisting deficiency.

B. Vitamin D - (1, 25 OH2 D3) Deficiency produces osteomalacia (called rickets in children). Many of the effects of osteomalacia overlap with the more common osteoporosis, but the two disordersare significantly different.
-> The specific alteration in osteomalacia and rickets is a failure of mineralization of the osteoid matrix resulting in decreased appositional bone growth. 

C. Vitamin E - Very rare. Occurs as a secondary disorder in conditions associated with fat maladsorption such as cystic fibrosis, pancreatitis, and cholestasis (bile-flow obstruction).
-> Vitamin E deficiency causes a neurological disorder characterized by sensory loss, ataxia and retinitis pigmentosa due to free radical mediated neuronal damage.

D. Vitamin K - (phylloquinone) Present in most leafy plants and also synthesized by intestinal bacteria. Vitamin K is required for the production of specific clotting factors and a deficiency is characterized by impaired coagulation (elevated clotting times). Although this can occur in newborns that are given breast milk low in vitamin K, the deficiency is almost always secondarily associated with the use of certain anti-coagulants or disorders such as obstructive jaundice, celiac, or pancreatic disease.

 E. Thiamine - (B1) The deficiency is known as beriberi. Thiamine deficiency is characterized by a peripheral neuropathy that affects sensation particularly in the legs (associated with demyelination of peripheral nerves), in more severe cases Korsakoff syndrome (neuropathy characterized by impaired ocular motility, ataxia, and mental confusion) and cardiomyopathy can occur.

F. Nicotinamide (niacin) - The deficiency is known as pellagra. Primary deficiencies are associated with diets that consist primarily of a single low quality protein source (i.e. corn). It results most commonly as a complication of alcoholism.

-> The pathology is characterized by hyperkeratosis and vesiculation of skin, atrophy of the tongue epithelium, and a neuropathy that can affect cortex and peripheral neurons.

- Initial symptoms include a smooth, red tongue, a sore mouth, and ulceration of the inside of the cheeks.

- The skin on the neck, chest, and back of the hands may become brown and scaly. 

- Often there is nausea, vomiting, and diarrhea. There may also be insomnia, depression, confusion, and rapid changes of mood. Long-standing pellagra can result in dementia and death.

G. Vitamin B12 - (cobalamin) Because cobalamin is synthesized by intestinal bacteria and is widely available in many foods, deficiencies are almost always secondary disorders associated with gastric atrophy (and decreased uptake via intrinsic factor), microbial proliferation (AIDS), long-term antacids, chronic alcoholism, idiopathic (age-related).

In addition to anemia, the primary clinical symptoms include a sensory neuropathy (polyneuropathy), sclerosis of the spinal cord and atrophy of some mucous tissues.

H. Vitamin C - (ascorbic acid) The classic deficiency is known as scurvy. The essential pathology involves an inability to produce mature collagen and hence affects connective tissue.

This is characterized by an inability to synthesize osteoid and dentin (and results in decreased wound healing) and a loss of integrity of blood vessel walls.

Oral lesions are only a feature of the advanced form of the disease; early signs include fatigue, dermatitis, and purpura. There can be abnormalities in the growing bones of infants. 

I. Vitamin B6 - (Pyridoxine) A deficiency can lead to peripheral neuropathy, most commonly associated with multivitamin B deficiencies in malnutrition and alcoholism. 

V. Major Minerals - Sodium, potassium, chlorine, and magnesium are required for life but dietary deficiencies do not develop.
A. Iodine - Essential for the synthesis of thyroid hormones, and severe iodine deficiency is  associated with hypothyroidism. The compensatory activity of the thyroid gland causes a  characteristic enlargement called goiter.

B. Calcium - Required for bone mineralization, the RDA for adults is 800 mg/day. Clinical trials have shown that 1000-2000 mg/day can delay the bone loss observed in the elderly and decrease the risk of osteoporosis. See also section IV B.

VI. Trace Elements - At least 10 elements (examples: Co, Mn, Si) are required in minute amounts for normal development and metabolism.

A. Zinc - A deficiency can result from inadequate amounts given during total parenteral nutrition or as a secondary effect of acrodermatitis enteropathica (autosomal recessive trait characterized by alopecia, dermatitis, and diarrhea - the disease responds to administration of zinc).

B. Copper - Deficiencies are rare and primarily associated with malabsorption syndromes and total parenteral nutrition. Copper is required for normal hematopoiesis and bone growth. A deficiency resembles iron deficiency anemia and osteoporosis.

C. Fluoride - Levels in drinking water greater than 1 ppm cause mottling of teeth and in areas with chronic naturally induced fluorosis there is abnormal calcification of ligaments and tendons.

Glomerulonephritis

Characterized by inflammation of the glomerulus.

Clinical manifestations:
Nephrotic syndrome (nephrosis) → Most often caused by glomerulonephritis.

Laboratory findings:
(i) Proteinuria (albuminuria) and lipiduria—proteins and lipids are present in urine.
(ii) Hypoalbuminemia—decreased serum albumin due to albuminuria.
(iii) Hyperlipidemia—especially an increase in plasma levels of low-density lipoproteins and cholesterol.

Symptoms

severe edema, resulting from a decrease in colloid osmotic pressure due to a decrease in serum albumin.

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.