4. Regulation of plasma calcium level
Dependent on the function of 3 main organs
Bone
Kidney
Intestine
3 main hormones
Calcitriol
Parathyroid hormone
Calcitonin
5. Regulation of plasma calcium level by Calcitriol
Role of calcitriol on bone:
In osteoblasts of bone, calcitriol stimulates calcium uptake for
deposition as calcium phosphate
At low calcium levels, calcitriol along with parathyroid hormone
increases the mobilization of calcium & phosphate from the bone
Causes elevation in the plasma calcium and phosphate
6. Role of calcitriol on kidneys
Calcitriol minimizing the excretion of Ca2+ & phosphate by decreasing
their excretion & enhancing reabsorption.
Role of calcitriol on intestine:
It increases intestinal absorption of Ca2+ & phosphate.
It binds with cytosolic receptor to form calcitriol-receptor complex
Complex interacts with DNA leading to the synthesis of a specific
calcium binding protein
This protein increases calcium uptake by intestine
7. Regulation by parathyroid hormone (PTH)
PTH is secreted by two pairs of parathyroid glands.
PTH (mol. wt. 95,000) is a single chain polypeptide, containing 84 amino
acids.
It is synthesized as prepro PTH, whch is degraded to proPTH & finally
to active PTH.
The rate of formation & secretion of PTH are promoted by low Ca2+
concentration.
8. Mechanism of action of PTH
Action on the bone:
PTH causes decalcification or demineralization of bone, a process carried
out by osteoclasts.
This is brought out by pyrophosphatase & collagenase
These enzymes result in bone resorption.
Demineralization ultimately leads to an increase in the blood Ca2+ level.
9. Action on the kidney
PTH increases the Ca2+ reabsorption by kidney tubules
It is most rapid action of PTH to elevate blood Ca2+ levels
PTH promotes the production of calcitriol (1,25 DHCC) in the kidney by
stimulating 1- hydroxylation of 25-hydroxycholecalciferol
Action on the intestine:
It increases the intestinal absorption of Ca2+ by promoting the synthesis
of calcitriol.
10.
11. Calcitonin
Calcitonin is a peptide containing 32 amino acids.
It is secreted by parafollicular cells of thyroid gland.
The action of CT on calcium is antagonistic to that of PTH.
Calcitonin promotes calcification by increasing the activity of osteoblasts.
Calcitonin decreases bone resorption & increases the excretion of Ca2+
into urine
Calcitonin has a decreasing influence on blood calcium
13. Absorption, transport & storage
Absorption:
Upper small intestine & in ferrous form
Iron is called as one way substance, because it is absorbed
& excreted from small intestine.
14. Transport of Iron
Iron in the mucosal cells:
The iron (Fe2+) entering the mucosal cells by absorption is
oxidized to ferric form (Fe3+) by the enzyme ferroxidase
(ferroxidase activity of ceruloplasmin)
Major sources of iron in the plasma is from degraded
erythrocytes.
Fe3+ combines with apoferritin to form ferritin.
15. From the mucosal cells, iron may enter the blood stream.
Transport of iron in the plasma:
Iron enters plasma in ferrous state.
It is oxidized to ferric form by ceruloplasmin - ferroxidase
activity.
Ferric iron binds with a specific iron binding protein-
transferrin or siderophilin.
Transport form of iron is transferrin.
It is a glycoprotein, synthesized in liver.
16. Normal plasma level of transferrin: 250 mg/dl.
Normal plasma iron: 50-150 μg/dl.
Serum iron and serum iron binding capacity:
Total iron binding capacity (TIBC) of transferrin is 250-450
µg/dl;
In iron deficiency anemia, serum iron level is decreased
and TIBC is increased.
17. Storage
Ferritin is the storage form.
Stored in intestinal mucosal cells, liver, spleen & bone marrow.
In the mucosal cells, ferritin is the temporary storage form of
iron.
Ferritin level in plasma (males: 25-380 ηg/ml, females: 15-150
ηg/ml) is elevated in iron over load.
18. Ferritin level in blood is an index of body iron stores.
Ferritin is an acute phase protein/reactant, elevated in
inflammatory diseases.
Hemosiderin:
It is formed by partial degradation of ferritin.
Present in liver, spleen & bone marrow.
Hemosiderin accumulates when iron levels are increased.
20. Disorders of iron metabolism
Iron deficiency & iron overload.
Iron deficiency
Iron deficiency causes a reduction in the rate of hemoglobin
synthesis & erythropoiesis.
It can result in iron deficiency anemia (microcytic
hypochromic anemia).
21. Causes:
Caused by inadequate intake, impaired absorption,
chronic blood loss & increased demand.
Iron deficiency anemia mostly occurs in growing children,
adolescent girls, pregnant & lactating women.
22. Clinical features
Microcytic hypochromic anemia.
Weakness, fatigue, dizziness and palpitation,
Laboratory findings:
Serum iron level is decreased & TIBC level is increased.
Treatment: 100 mg of iron & 500 mg of folic acid to pregnant
women.
20 mg of iron & 100 mg of folic acid to children.
23. Iron over load
Hemosiderosis and hemochromatosis are conditions
associated with iron over load.
Hemosiderosis:
Accumulation of hemosiderin in liver & other reticulo-
endothelial system.
There is no significant tissue destruction.
Hemosiderosis is an initial stage of iron over load.
24. Hemochromatosis
Hemochromatosis: In liver, hemosiderin deposit leads to
death of cell & cirrhosis.
Pancreatic cell death leads to diabetes.
Deposits under skin cause yellow-brown discoloration,
called hemochromatosis.
Hemochromatosis & diabetes are referred to as bronze
diabetes.
25. Case report - 25
A 34 year old women visited general practitioner because of dizziness &
excessive tiredness. She was out of breath with little walking. She
always stuck to a strict vegetarian diet. On examination, she had pallor
and spooning of nails (koilonychia). Interpret the following laboratory
findings.
Investigations Report
Hemoglobin 8.7 g%
Random blood sugar 106 mg/dl
Serum total protein 7 g/dl
Blood smear Microcytic & hypochromic RBCs
27. Biochemical functions
Copper is an essential constituent of several enzymes.
1. These include
1. Cytochrome oxidase,
2. Catalase,
3. Tyrosinase,
4. Superoxide dismutase,
5. Monoamine oxidase,
6. Ascorbic acid oxidase,
7. ALA synthase and uricase.
28. 2. Lysyl oxidase (a copper-containing enzyme) is required for the
conversion of certain lysine residues of collagen & elastin to allysine
which are necessary for cross-linking.
3. Ceruloplasmin serves as ferroxidase & is involved in conversion of
iron from Fe2+ to Fe3+
4. Copper is necessary for the synthesis of melanin & phospholipids
5. Development of bone & nervous system (myelin) requires Cu.
29. Menke’s kinky hair syndrome
Caused by defect in the transport of copper from mucosal cell to blood.
This results in deficiency of copper.
Features:
Decreased copper in plasma & urine, anemia, depigmentation of hair
(kinky hair or silky hair), growth failure, mental retardation, vascular
defects (lesions of the blood vessels).
Treatment: No effective treatment.
Abnormal metabolism of copper
30.
31. Wilson’s disease
Wilson’s disease (hepatolenticular degeneration) is a rare genetic
disorder.
Caused by defect in the transport of copper & secretion of ceruloplasmin
from the liver.
Accumulation of copper in the liver & other tissues of the body.
Fatal and death occurs at early life.
32.
33. Characteristics
Copper is deposited in liver & lenticular nucleus of brain.
Leads to hepatic cirrhosis & brain necrosis.
Low levels of copper & ceruloplasmin in plasma with increased
excretion of copper in urine.
Copper deposition in kidney causes renal damage.
Leads to increased excretion of amino acids, glucose, peptides &
hemoglobin in urine.
Intestinal absorption of copper is very high.
34. Symptoms:
Liver damage leading to cirrhosis, renal tubular damage and Kayser-
Fleisher rings (brown pigment around the iris) at the edges of the
cornea.
Treatment:
Includes diet low in copper & administration of copper chelator, D-
penicillamine.
37. Biochemical functions
Zinc is component of many metalloenzymes.
Carbonic anhydrase
Alkaline phosphatase
Alcohol dehydrogenase
Lactate dehydrogenase
Carboxy-peptidase
Superoxidase dismutase (cytosol) – anti-oxidant
DNA and RNA polymerases
38. Zn is necessary for
Storage & secretion of insulin
To maintain normal levels of vitamin A.
Synthesis of RBP.
Proper reproduction, growth & division of cells
Important element in wound healing.
Stabilizes membrane structure, structure of protein & nucleic acids.
Gusten, a zinc containing protein of the saliva, is important for
taste sensation
39. Normal plasma level: 100 mg/dl
Deficiency:
Causes:
Dietary deficiency
Malabsorption
Chronic alcoholism
Parental nutrition with inadequate zinc.
Symptoms:
Impaired spermatogenesis
Growth failure, Impaired wound healing
Skin lesions such as dermatitis
41. Functions
Selenium is involved in
Along with vitamin E, prevents the development of hepatic
necrosis and muscular dystrophy
Maintaining structural integrity of biological membranes
As selenocysteine, essential component of glutathione
peroxidase, protects cells from H2O2.
Prevents lipid peroxidation & protects cells against free radicals
42. Selenium protects animals from carcinogenic chemicals.
Selenium binds with certain heavy metals & protects the body from
their toxic effects
A selenium containing enzyme 5’-deiodinase converts thyroxine (T4)
to triiodo-thyronine (T3) in thyroid gland
43. Deficiency
Causes:
Low soil content of selenium & malnutrition.
Clinical features:
Chronic selenium deficiency is associated with
Cirrhosis of liver
Cardiomyopathy leading to congestive cardiac failure
Muscular dystrophy
Loss of appetite & nausea
Abnormal electrocardiograms.
