Page 266 - Textbook of Pathology, 6th Edition

250 Biochemical changes. These are as follows: in the form of chylomicrons. It is stored in fat depots, liver
i) Lowered levels of active metabolites of vitamin D (25- and muscle.
hydroxy vitamin D and 1, 25-dihydroxy vitamin D). The main physiologic functions of vitamin E are as
ii) Plasma calcium levels are normal or slightly low. under:
iii) Plasma phosphate levels are lowered. 1. Anti-oxidant activity. Active form of Vitamin E acts as an
iv) Plasma alkaline phosphatase is usually raised due to antioxidant and prevents the oxidative degradation of cell
osteoblastic activity. membranes containing phospholipids.
Vitamin D-dependent rickets is an autosomal dominant 2. Scavenger of free radicals. Vitamin E scavenges free radicals
disorder of vitamin D. The disease responds rapidly to formed by redox reaction in the body (Chapter 3) and thus
SECTION I
administration of 1,25-dihydroxy vitamin D. maintains the integrity of the cell.
3. Inhibits prostaglandin synthesis.
OSTEOMALACIA. Osteomalacia is the adult counterpart
of rickets in which there is failure of mineralisation of the 4. Activates protein kinase C and phospholipase A .
2
osteoid matrix. It may occur following dietary deficiency, LESIONS IN VITAMIN E DEFICIENCY. The deficiency of
poor endogenous synthesis of vitamin D, or as a result of vitamin E is mainly by conditioning disorders affecting its
conditioned deficiency. absorption and transport such as abetalipoproteinaemia,
intra- and extrahepatic biliary cholestasis, cystic fibrosis of
MORPHOLOGIC FEATURES. Due to deficiency of the pancreas and malabsorption syndrome. Low birth weight
vitamin D, osteoid matrix laid down fails to get minera- neonates, due to physiologic immaturity of the liver and
lised. In H and E stained microscopic sections, this is bowel, may also develop vitamin E deficiency. Lesions of
identified by widened and thickened osteoid seams vitamin E deficiency are as follows:
(stained pink) and decreased mineralisation at the borders 1. Neurons with long axons develop degeneration in the
between osteoid and bone (stained basophilic). von Kossa’s posterior columns of spinal cord.
stain for calcium may be employed to mark out the wide 2. Peripheral nerves may also develop myelin degeneration
seams of unstained osteoid while the calcified bone is in the axons.
stained black. In addition, there may be increased 3. Skeletal muscles may develop denervation.
osteoclastic activity and fibrosis of marrow. 4. Retinal pigmentary degeneration may occur.

Clinical features. Osteomalacia is characterised by: 5. Red blood cells deficient in vitamin E such as in premature
i) muscular weakness; infants have reduced lifespan.
ii) vague bony pains; 6. In experimental animals, vitamin E deficiency can pro-
General Pathology and Basic Techniques
iii) fractures following trivial trauma; duce sterility in both male and female animals.
iv) incomplete or greenstick fractures; and
v) looser’s zones or pseudofractures at weak places in bones. Vitamin K
Biochemical changes. These are: PHYSIOLOGY. Vitamin K (K for Koagulations in Danish)
i) normal or low serum calcium levels; exists in nature in 2 forms:
ii) plasma phosphate levels lowered; and Vitamin K or phylloquinone, obtained from exogenous
1
iii) raised serum alkaline phosphatase due to increased dietary sources such as most green leafy vegetables; and
osteoblastic activity. Vitamin K or menaquinone, produced endogenously by
2
It may be worthwhile to note here that another chronic normal intestinal flora. Phylloquinone can be converted into
disorder of skeleton seen in elderly, osteoporosis, is clinically menaquinone in some organs.
similar but biochemically different disease (Chapter 28). Like other fat-soluble vitamins, vitamin K is absorbed
from the small intestine and requires adequate bile flow and
HYPERVITAMINOSIS D. Very large excess of vitamin D intact pancreatic function.
may cause increased intestinal absorption of calcium and The main physiologic function of vitamin K is in hepa-
phosphorus, leading to hypercalcaemia, hyperphos- tic microsomal carboxylation reaction for vitamin K-
phataemia and increased bone resorption. These changes dependent coagulation factors (most importantly factor II or
may result in the following effects: prothrombin; others are factors VII, IX and X).
i) increased urinary excretion of calcium and phosphate;
ii) predisposition to renal calculi; LESIONS IN VITAMIN K DEFICIENCY. Since vitamin K
iii) osteoporosis; and is necessary for the manufacture of prothrombin, its
iv) widespread metastatic calcification, more marked in the deficiency leads of hypoprothrombinaemia (Chapter 13).
renal tubules, arteries, myocardium, lungs and stomach. Estimation of plasma prothrombin, thus, affords a simple in
vitro test for determining whether there is deficiency of
vitamin K. Subjects with levels below 70% of normal should
Vitamin E (αα αα α-Tocopherol)
receive therapy with vitamin K.
PHYSIOLOGY. Out of many naturally-occurring tocoferols Because most of the green vegetables contain vitamin K
and tocotrienols, α-tocopherol is biologically the most active and that it can be synthesised endogenously, vitamin K
fat soluble compound for humans. Vitamin E is found in most deficiency is frequently a conditioned deficiency. The
of the ordinary foods such as vegetables, grains, nuts and conditions which may bring about vitamin K deficiency are
oils. It is absorbed from the intestine and transported in blood as follows: