Pemphigus
1. Ulcerative lesions on the skin and oral mucosa.
2. An autoimmune disease in which patients have autoantibodies against hemidemosomal attachment of epidermis cells.
3. Histologically characterized by acantholysis, in which epidermal cells appear to detach and separate from each other, as seen by Tzanck smears.
4. Can be life-threatening if untreated.
5. A positive Nikolsky sign is observed.
Because of sloughing of the epidermis, a red blister forms after pressure is applied to affected skin.
6. Treatment: corticosteroids.

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.

Wilson’s disease

Caused by a decrease in ceruloplasmin, a serum protein that binds copper, resulting in metastatic copper deposits.

Common organs affected include:

(1) Liver, leading to cirrhosis.

(2) Basal ganglia.

(3) Cornea, where Kayser-Fleischer rings (greenish rings around the cornea) are observed.

Thalassaemia. Genetic based defect in synthesis of one of the normal chains.

Beta thalassaemia --->  reduced Hb A and increased HbF (α2, Y2) HBA2(α2)

Alpha thalassaemia  --->   reduced  Hb-A, Hb-A2 and Hb-F-with formation of Hb-H(β4) and Hb Barts (Y4).
Thalassaemia may manifest as trait or disease or with intermediate manifestation.

Features:
•    Microcytic hypochromic RBC is in iron deficjency.
•    Marked anisopoikilocytsis  with prominent target cells.
•    Reticulocytosis and nucleated RBC seen.
•    Mongoloid facies and X-ray findings characteristic of marrow hyperplasia
•    Decreased osmotic. fragility.
•    Increased marrow iron (important difference from iron deficiency anaemia).
•    Haemosiderosis, especially with repeated transfusions.

Diagnosis is by Hb electrophoresis and by Alkali denaturation test (for HbF).

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.

Metastatic Tumors 

These are the most common malignant tumor of bone. Certain tumors exhibit a distinct skeletal prediliction. In adults more than 75% of skeletal metastases originate from cancers of the prostate, breast, kidney, and lung. In children, neuroblastoma, Wilms' tumor, osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma are the common sources of bony metastases. Most metastases involve the axial skeleton (vertebral column, pelvis, ribs, skull, sternum), proximal femur, and humerus. The radiologic appearance of metastases can be purely osteolytic, purely osteoblastic, or mixed osteolytic-osteoblastic (majority of cases). In lytic lesions (e.g., kidney& lung), the metastatic cells secrete substances such as prostaglandins, interleukins, etc. that stimulate osteoclastic bone resorption; the tumor cells themselves do not directly resorb bone. Similarly, metastases that elicit a blastic response (e.g., prostate adenocarcinoma) do so by stimulating osteoblastic bone formation.