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Title: Pathological calcification
Description: Notes on the topic of pathological calcification for a cellular pathology and special topics in pathobiology taught on the third year of a biomedical science degree. Notes cover; bone physiology, calcium homeostasis, the action of parathyroid hormone, secondary hyperparathyroidism, the basics of pathological calcification, dystrophic calcification, and metastatic calcification.
Description: Notes on the topic of pathological calcification for a cellular pathology and special topics in pathobiology taught on the third year of a biomedical science degree. Notes cover; bone physiology, calcium homeostasis, the action of parathyroid hormone, secondary hyperparathyroidism, the basics of pathological calcification, dystrophic calcification, and metastatic calcification.
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Gv
Pathological calcification
Bone
Cortical bone is the dense outer surface of the bone that forms a protective layer around the
internal cavity
...
Cortical bone is found in
the shaft of long bones and forms the outer shell around cancellous bone, also called
trabecular bone or spongy bone, is a light, porous bone enclosing numerous large spaces
that give a honeycombed or spongy appearance
...
The spaces between are filled with marrow
...
Cancellous bone is found at the ends of long bones, as well as in the pelvic bones,
ribs, skull, and the vertebrate in the spinal column
...
All are continually in a state of change, the cells die off and are
replaced, the collagen and minerals are eroded and reformed
...
Together, the
two processes constitute bone remodelling
...
Bone is formed by
the collagen matrix becoming mineralized
...
Hydroxyapatite is composed mainly of hydrated calcium phosphate,
but also contains traces of carbonate, citrate, and other ions
...
The embryonic skeleton is formed by;m endochondral ossification in which a bone
develops by replacing hyaline cartilage and the resulting bone is called cartilage or
endochondral bone, and intramembranous ossification in which a bone develops from a
fibrous membrane and the resulting bone is called membrane bone
...
Most bones stop growing during adolescence
...
Osteoblasts are mononucleated cuboidal cells that originate from immature mesenchymal
stem cells
...
Osteoblasts from bone by
producing a matrix that then becomes mineralised
...
They are networked to each other via long cytoplasmic
extensions that occupy tiny canals called canaliculi, which are used for exchange of nutrients
and waste through gap junctions
...
Osteoclasts are bone resorbing cells
...
This parameter is tightly controlled because calcium ions have a stabilising effect on
voltage-gated ion channels
...
Causing hyperactivity of nerve and muscle cells
...
Conversely, hypercalcaemia results in closure of voltage gated ion channels and consequent
depressed nervous system function
...
Parathyroid hormone
In the blood, the sensitive process of calcium and phosphate homeostasis is maintained
primarily by the parathyroid gland
...
The two
parathyroid glands on each side that are positioned higher are called the left and right
superior parathyroid glands, while the lower two are called the left and right inferior
parathyroid glands
...
PTH is a polypeptide that is synthesized and cleaved into an active form within the
parathyroid gland
...
as
serum calcium levels drop, PTH secretion increases
...
in
the bones, PTH stimulates the release of calcium in an indirect process through osteoclasts
which ultimately results in bone resorption
...
PTH also inhibits the
secretion of osteoprotegerin, allowing for preferential differentiation into osteoclasts
...
Osteoclasts possess the ability to remodel the bones by dissolution and
degradation of hydroxyapatite and other organic material releasing calcium into the blood
...
PTH decreases phosphate reabsorption at the
proximal convoluted tubule of the kidney
...
The reduction of phosphate
ions, therefore, results in more ionized calcium in the blood
...
1-alpha-hydroxylase catalyses the synthesis of active vitamin D-1,
25-dihydroxycholecalciferol from the inactive form, 25-hydroxycholecalciferol
...
calcitonin , a hormone produced by the parafollicular cells of the thyroid, acts in opposition to
PTH by inhibiting osteoclasts, stimulating osteoblasts, and increasing excretion of calcium in
the urine by the kidneys
...
Secondary hyperparathyroidism is primarily seen in patients with chronic kidney
disease (CKD)
...
Significant decrease in the expression of klotho, and a reduction
of renal calcitriol production
...
indirectly , calcitriol deficiency also stimulates PTH secretion due to a decrease in intestinal
calcium absorption
...
The drug cinacalcet is a calcimimetic drug that binds to the
calcium sensing receptors on cells of the parathyroid gland, inhibiting PTH secretion
...
Procedures include;
paraffin or frozen sections after decalcification, ground sections, or resins
...
Biopsies investigating possible tumors or infection
are decalcified in acid or with a chelating agent and processed routinely
...
X-ray
may provide information on; nature and extent of bone lesion, which blocks required for
staining, the progress of decalcification, and whether foregin material is present such as
metal
...
Trichrome stains collagen, PAS stains osteoid, alizarin red stains calcium, phosphates and
carbonate
...
Fluorescent labelling may be used in metabolic investigation, and is based on
the uptake in vivo of tetracycline
...
The biopsy is processed into resin, and viewed unstained with a short wave ultraviolet
light
...
Morphometry can also be used to assess the effects of a
treatment regimen, for example in hyperparathyroid bone disease
...
Pathologic calcification can
occur in almost any tissue structure
...
The first detectable mineral deposited in vivo is a poorly crystallised
apatite which perfects with age
...
Also commonly in pathology is
primary nucleation, where crystals grow on a different surface, by epitaxy
...
Mitochondria frequently initiate intracellular calcification
...
Matrix vesicles and mitochondria
usually initiate calcification through the interaction of phosphatase enzymes with
calcium-binding phospholipids, both of which are membrane bound
...
Once formed and exposed to the extracellular fluid, HA crystals can serve as
nuclei or templates, thus supporting progressive, autocatalytic mineral crystal proliferation
...
The cell membrane pumps
calcium out of the cell, the mitochondrial membrane pumps calcium into the mitochondria
...
The calcified mitochondria are then available for secondary
nucleation
...
It is associated with multiple clinical conditions, such as collagen vascular
diseases
...
Dystrophic calcification occurs when a local disturbance
in serum calcium levels leads to crystal formation
...
Metabolic calcification occurs
in situations of systemic disturbances of serum calcium levels, and crystals are deposited
throughout the body
...
Metastatic calcification
deposition can be influenced by release of excess calcium salts from bone, phosphate
concentration, alkaline phosphatase activity and viscera physiochemical conditions under
alkalosis
...
Bacteria can also initiate calcification, for example the bacteria bacteremia matruchotii
yielded the first phospholipid and protein complex capable of nucleating apatite in vitro
...
Actinomyces is a genus of the actinobacteria
class of bacteria
...
Actinomyces species are facultative;y
anaerobic
...
Spicules are any of various small
needle-like anatomical structures occurring in organisms
...
Mammograms can detect benign calcifications of
mammary tissues visible as white patches, as well as showing calcification typical for tumour
in the mammography tissue
Title: Pathological calcification
Description: Notes on the topic of pathological calcification for a cellular pathology and special topics in pathobiology taught on the third year of a biomedical science degree. Notes cover; bone physiology, calcium homeostasis, the action of parathyroid hormone, secondary hyperparathyroidism, the basics of pathological calcification, dystrophic calcification, and metastatic calcification.
Description: Notes on the topic of pathological calcification for a cellular pathology and special topics in pathobiology taught on the third year of a biomedical science degree. Notes cover; bone physiology, calcium homeostasis, the action of parathyroid hormone, secondary hyperparathyroidism, the basics of pathological calcification, dystrophic calcification, and metastatic calcification.