Megaloblastic anaemia

Metabolism: B12(cyanocobalamin) is a coenzyme in DNA synthesis and for maintenance of nervous system. Daily requirement 2 micro grams. Absorption in terminal ileum in the presence gastric intrinsic factor. It is stored in liver mainly-

Folic acid (Pteroylglutamic acid) is needed for DNA synthesis.. Daily requirement 100 micro grams. Absorption in duodenum  and jejunum

Causes of deficiency .-

- Nutritional deficiency-
- Malabsorption syndrome.
- Pernicious anaemia (B12).
- Gastrectomy (B12).
- Fish tapeworm infestation (B12).
- Pregnancy and puerperium (Folic acid mainly).
- Myeloproliferative disorders (Folic acid).
- Malignancies (Folic acid).
- Drug induced (Folic-acid)

Features:

(i) Megaloblastic anaemia.
(ii) Glossitis.
(iii) Subacute combined degeneration (in B12deficiency).

Blood picture :

- Macrocytic normochromic anaemia.
- Anisocytosis and poikilocytosis with Howell-Jolly bodies and  basophilic stippling.
- Occasional megalo blasts may be-seen.
- Neutropenia with hypersegmented neutrophills and macropolycytes.
- Thrombocytopenia.
- Increased MVC and MCH with normal or decreased MCHC.

Bone marrow:

- Megaloblasts are seen. They are larger with a more open stippled chromatin. The nuclear maturation lags behind. the cytoplasmic maturation. Maturation arrest is seen (more of early forms).
- Immature cells of granulocyte series are also larger.
 -Giant stab forms (giant metamyelocytes).
 

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

(1) 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

(2) 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).

1. 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.
 

Acne vulgaris is a chronic inflammatory disorder usually present in the late teenage years characterized by comedones, papules, nodules, and cysts.
 - subdivided into obstructive type with closed comedones (whiteheads) and open comedones (blackheads) and the inflammatory type consisting of papules, pustules, nodules, cysts and scars.
 - pathogenesis of inflammatory acne relates to blockage of the hair follicle with keratin and sebaceous secretions, which are acted upon by Propionibacterium acnes (anaerobe) that causes the release of irritating fatty acids resulting in an inflammatory response.
 - pathogenesis of the obstructive type (comedones) is related to plugging of the outlet of a hair follicle by keratin debris.
 - chocolate, shellfish, nuts iodized salt do not aggravate acne.
 - obstructive type is best treated with benzoyl peroxide and triretnoin (vitamin A acid)
 - treatment of inflammatory type is the above plus antibiotics (topical and/or systemic; erythromycin, tetracycline, clindamycin).

Biochemical examination

This is a method by which the metabolic disturbances of disease are investigated by assay of various normal and abnormal compounds in the blood, urine, etc.

HYPERTROPHY
Increase in the size of an organ or tissue due to increase in the size of its Constituent cells.

1. Skeletal muscle due to -exercise.

2. Cardiac muscle of:
- Left ventricle in:
    o    Hypertension.
    o    Aortic valvular lesion.
    o    Severe anaemia.
- Right ventricle in :
    o    Mitral stenosis
    o    Cor pulmonale
    
3. Smooth muscle of:

- GIT proximal to strictures.
- Uterus in pregnancy.
 

Primary vs. secondary disorders - Most nutritional disorders in developed countries are not due to simple dietary deficiencies but are rather a secondary manifestation of an underlying primary condition or disorder.

• Chronic alcoholism
• Pregnancy and lactation
• Renal dialysis
• Eating disorders
• Prolonged use of diuretics
• Malabsorption syndromes
• Neoplasms
• Food fads
• Vegans
• AIDS