Clinical genetics (cytogenetics),

This is a method in which inherited chromosomal abnormalities in the germ cells or acquired chromosomal abnormalities in somatic cells are investigated using the techniques of molecular biology.

Paget Disease (Osteitis Deformans) 

This unique bone disease is characterized by repetitive episodes of exaggerated, regional osteoclastic activity (osteolytic stage), followed by exuberant bone formation (mixed osteoclastic-osteoblastic stage), and finally by exhaustion of cellular activity (osteosclerotic stage). The net effect of this process is a gain in bone mass; however, the newly formed bone is disordered and lacks strength. Paget disease usually does not occur until mid-adulthood but becomes progressively more common thereafter. The pathognomonic histologic feature is a mosaic pattern of lamellar bone (likened to a jigsaw puzzle) due to prominent cement lines that haphazardly fuse units of lamellar bone. (Fig. 12-5) The axial skeleton and proximal femur are involved in the majority of cases. In patients with extensive disease, hypervascularity of the marrow spaces can result in high-output congestive heart failure. Cranial nerves impingement also occurs and can lead to head ache and auditory disturbances. Rarely Paget disease is complicated by bone sarcoma (usually osteogenic). 

Anemia (Disorder of Hematopoietic System) - Probably the most common effect of nutritional deficiency. Any factor that decreases hematopoiesis can cause an anemia.

A. Iron deficiency - Widely recognized as the most important cause of anemia, It is indicated that ½ of all pregnant women and infants are affected, as are ~13% of all adult women.

1. Dietary factors - Availability of iron from different food sources and mixtures.
2. Malabsorption – One third of patients with inflammatory bowel disease (IBD) have recurrent anemia and 30% or more of patients who have had partial gastrectomy will develop iron deficiency anemia.
3. Blood loss - Menses, gastrointestinal bleeding 
4. Increased demand - Pregnancy, growth in children.
5. Congenital - Atransferrinemia
6. Importance of multiple factors.
7. Pathophysiology - Initially iron is mobilized from reticuloendothelial stores and increased intestinal absorption occurs. Total iron stores are depleted, serum iron levels fall. In severe cases in peripheral blood, the red cells become smaller (microcytic) and their hemoglobin content is reduced (hypochromic).  

B. Megaloblastic anemias- Characterized by the presence of abnormal WBCs and RBCs. In severe cases, megaloblasts (abnormal red cell precursors) may be present. These anemias are a consequence of disordered DNA synthesis.
1. Folate deficiency - Can be caused by:
a. Dietary deficiency
b. Malabsorption (celiac disease)
c. Increased demand (pregnancy & lactation)
d. Drugs - methotrexate, anticonvulsants, oral contraceptives, alcoholism.
e. Liver disease

2. Cobalamin (vitamin B12) deficiency - Almost always a secondary disorder that can  be caused by:

a. Intrinsic factor deficiency (pernicious anemia due to autoimmune destruction of the gastric mucosa)

b. Malabsorption

3. Pyridoxine (vitamin B6) deficiency- most commonly associated with alcoholism.

C. Other factors known to be frequently associated with anemia would include protein-calorie malnutrition, vitamin C deficiency, and pyridoxine deficiency (usually associated with alcoholism).

D. Other anemias not particularly associated with nutritional disease would include hemolytic anemia
(decreased red cell life span) and aplastic anemia (failure of marrow to produce new cells).  

Parathyroid hormone 

Parathyroid hormone (PTH) is a polypeptide (84 amino acid residues) secreted by the chief cells of the parathyroid glands (four glands: two in each of the superior and inferior lobes of the thyroid; total weight 120 mg).

The main action of PTH is to increase serum calcium and decrease serum phosphate.

Its actions are mediated by the bones and kidneys -
In bone, PTH stimulates osteoclastic bone resorption and inhibits osteoblastic bone deposition. The net effect is the release of calcium from bone.
In the kidney, PTH has the following effects:
- Increases calcium reabsorption.
- Decreases phosphate reabsorption.
- Increases 1-hydroxylation of 25-hydroxyvitamin D (i.e. activates vitamin D).

PTH also increases gastrointestinal calcium absorption. 

Joint pathology
1. Rheumatoid arthritis
a. Cause is autoimmune in nature.
b. More common in women aged 20 to 50.
c. Characterized by inflammation of the synovial membrane. Granulation tissue, known as pannus, will form in the synovium and expand over the articular cartilage. This causes the destruction of the underlying cartilage and results in fibrotic changes and ankylosis.
Scarring, contracture, and deformity of the joints may occur.
d. Clinical symptoms include swollen joints. It can affect any joint in the body.

2. Osteoarthritis
a. Most common arthritis.
b. Cause is unknown.
c. Higher incidence in women, usually after age 50.
d. Characterized by degeneration of the articular cartilage and the formation of osteophytes (bony spurs) at the margins of affected areas.
Clinical signs and symptoms include:
(1) Stiff and painful joints affecting joints in the hand (phalangeal joints) and weight-bearing joints.
(2) Heberden’s nodes—nodules at the distal interphalangeal joint.
(3) Bocard’s nodes—nodules at the proximal interphalangeal joint.

Microbiological examination

 This is a method by which body fluids, excised tissue, etc. are examined by microscopical, cultural and serological techniques to identify micro-organisms Microbiological examination responsible for many diseases.