Nephritic syndrome

Characterized by inflammatory rupture of the glomerular capillaries, leaking blood into the urinary space.

Classic presentation: poststreptococcal glomerulonephritis. It occurs after a group A, β–hemolytic Streptococcus infection (e.g., strep throat.)

Caused by autoantibodies forming immune complexes in the glomerulus.

Clinical manifestations: 

oliguria, hematuria, hypertension, edema, and azotemia (increased concentrations of serum urea nitrogen
and creatine).

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.

Measles (rubeola) 

-incubation period 7 to 14 days 

-begins with fever (up to 40 degrees C), cough, conjunctivitis (photophobia is first sign), and coryza (excessive mucous production)Æfollowed by Koplik's spots (red with white center) in the mouth, posterior cervical Lymphadenopathy, and a generalized, blanching, maculopapular, brownish-pink rash (viral induced vasculitis) beginning at the hairline and extending down over the body which gradually resolves in 5 days with some desquamation. 

Multiple myeloma.

Blood picture:

- Marked rouleaux formation.
- Normpcytic normochromic anaemia.
- There may be leucopenia or leucoery!hrohlastic reaction.
- Atypical plasma cells may be seen in some patients
- Raised ESR
- Monoclonal hypergammaglobulinaemia 
- If light chains are produced in excess, they are excreted in urine as bence jones protein

Bone marrow

- Hyper cellular
- Plasma cells from at least 15 – 30% atypical forms and myeloma cells are seen.
 

Urticaria (hives) refers to the presence of edema within the dermis and itchy elevations of the skin which may relate to either a Type I (MC) or Type III hypersensitivity reaction.

Type III hypersensitivity reaction.

 - exaggerated venular permeability MC related to IgE mediated disease and release of histamine from mast cells.

Autoimmune Diseases
These are a group of disease where antibodies  (or CMI) are produced against self antigens, causing disease process.

Normally one's immune competent cells do not react against one's own tissues.
This is due to self tolerance acquired during embryogenesis. Any antigen encountered at
that stage is recognized as self and the clone of cells capable of forming the corresponding antibody is suppressed.

Mechanism of autoimmunity

(1) Alteration of antigen

 -Physicochemical denaturation by UV light, drugs etc. e.g. SLE.
- Native protein may turn antigenic  when a foreign hapten combines with it, e.g. Haemolytic anemia with Alpha methyl dopa.

(2) Cross reaction: Antibody produced against foreign antigen may cross react with native protein because of partial similarity e.g. Rheumatic fever.

(3) Exposure of sequestered antigens: Antigens not normally exposed to immune competent cells are not accepted as self as tolerance has not been developed to them. e.g. thyroglobulin, lens protein, sperms.

(4) Breakdown of tolerance : 
- Emergence of forbidden clones (due to neoplasia of immune system as in lymphomas and lymphocytic leukaemia)
- Loss of suppressor T cells as in old age and CMI defects

Autoimmunity may be
- Organ specific.
-  Non organ specific (multisystemic)

I. Organ specific.
(I) Hemolytic anaemia:
- Warm or cold antibodies (active at 37° C or at colder temperature)
- They may lyse the RBC by complement activation or coat them and make them vulnerable to phagocytosis

(ii) Hashimoto's thyroiditis:
 
- Antibodies to thyroglobulin and microsomal antigens.
- Cell mediated immunity.
- Leads to chronic. destructive thyroiditis.

(3) Pernicious anemia

Antibodies to gastric parietal cells and to intrinsic factor.

2. Non organ specific.

Lesions are seen in more than one system but principally affect blood vessels and connective tissue (collagen diseases).

(I) Systemic lupus erythematosus  (SLE). Antibodies to varied antigens are seen. Hence it is possible that there is abnormal reactivity of the immune system in self recognition.

Antibodies have been demonstrated against:

- Nuclear material (antinuclear I antibodies) including DNA. nucleoprotein etc. Anti nuclear antibodies are demonstrated by LE cell test.
- Cytoplasmic organelles- mitochondria, rib osomes, Iysosomes.
- Blood constituents like RBC, WBC. platelets, coagulation factors.

Mechanism. Immune complexes of body proteins and auto antibodies deposit in various organs and cause damage as in type III hypersensitivity

Organs involved
- Skin- basal dissolution and collagen degeneration with fibrinoid vasculitis.
- Heart- pancarditis.
- Kidneys- glomerulonephritis of focal, diffuse or membranous type 
- Joints- arthritis. 
- Spleen- perisplenitis and vascular thickening (onion skin).
- Lymph nodes- focal necrosis and follicular hyperplasia.
- Vasculitis in other organs like liver, central or peripheral nervous system etc,

2. Polyarteritis nodosa. Remittant .disseminated necrotising vasculitis of small and medium sized arteries

Mechanism :- Not definitely known. Proposed immune reaction to exogenous or auto antigens 

Lesion : Focal panarteritis- a segment of vessel is involved. There is fibrinoid necrosis with initially acute and later chronic inflammatory cells. This may result in haemorrhage and aneurysm.

Organs involved. No organ or tissue is exempt but commonly involved organs are :
- Kidneys.
- Heart.
- Spleen.
- GIT.

3. Rheumatoid arthritis. A disease primarily of females in young adult life. 

Antibodies

- Rheumatoid factor (An IgM antibody to self IgG)
- Antinuclear antibodies in 20% patients.

Lesions

- Arthritis which may progress on to a crippling deformity.
- Arteritis in various organs- heart, GIT, muscles.
- Pleuritis and fibrosing alveolitis.
- Amyloidosis is an important complication.

4. Sjogren's  Syndrome. This is constituted by 
- Kerato conjunctivitis sicca
- Xerostomia
- Rheumatoid arthritis. 

Antibodies

- Rheumatoid factor

- Antinuclear factors (70%).
- Other antibodies like antithyroid, complement fixing Ab etc
- Functional defects in lymphocytes. There is a higher incidence of lymphoma

5. Scleroderma (Progressive systemic sclerosis)
Inflammation and progressive sclerosis of connective tissue of skin and viscera.

Antibodies
- Antinuclear antibodies.
- Rheumatoid factor. .
- Defect is cell mediated.

lesions

- Skin- depigmentation, sclerotic atrophy followed by cakinosis-claw fingers and mask face.
- Joints-synovitis with fibrosis
- Muscles- myositis.
- GIT- diffuse fibrous replacement of muscularis resulting in hypomotility and malabsorption
- Kidneys changes as in SLE and necrotising vasculitis.
- Lungs – fibrosing alveolitis.
- Vasculitis in any organ or tissue.

6.Wegener’s granulomatosis. A complex of:

- Necrotising lesions in upper respiratory tract.
- Disseminated necrotising vasculitis.
- Focal or diffuse glomerulitis.

Mechanism. Not known. It is classed with  autoimmune diseases because of the vasculitis  resembling other immune based disorders.