Lect 4. - Parathyroid Flashcards
the parathyroid glands produce?
parathyroid hormone, which increases levels of calcium in the blood.
(calcitonin comes from thyroid gland C cells)
Describe the parathyroid glands
The parathyroid glands are small pea-sized glands located in the neck just behind the butterfly-shaped thyroid gland.
Calcitonin is
a hormone that is produced and released by the C-cells of the thyroid gland.
Inconditionsinwhichcalciumhomeostasisisunderstress(suchasrapidgrowth,over‐ orundersupplementation,orpregnancyandlactation)calciummetabolismisregulatedbythecalciotropichormones: (3)
parathyroidhormone(PTH)
calcitonin(CT)
vitaminD
Synthesisandreleaseofthe calciotropic hormonesaremainlytriggeredby
variationsinplasmacalciumconcentration.
Thelocationoftheparathyroidglands.
Thecranialor»external«parathyroids arelooselyattachedtothethyroidcapsule.
Thecaudalor»internal«parathyroids aresubcapsularandusually
embeddedinthyroidtissue.
Themajorcelloftheparathyroids is
thechiefcell.
The chief cells synthesize, store, and
secrete PTH.
Parathyroid hormone (PTH)is synthesized andsecreted inresponse to
hypocalcaemia
low blood levels ofcalcitriol (vitamin D3)
Anincreaseinplasmaphosphorusconcentration
Parathyroid hormone function (3)
The parathyroid hormone stimulates the following functions:
Release of calcium by bones into the bloodstream.
Absorption of calcium from food by the intestines.
Conservation of calcium by the kidneys.
Increases in extracellular [Ca2+]
inhibit
PTH secretion.
Increased [Ca2+] also inhibits PTH synthesis. Thus, increased levels of plasma Ca2+ lower PTH
release and therefore tend to lower plasma [Ca2+].
themostimportantdeterminantof PTHsecretion is the
thefractionofionizedcalcium in the blood
PTHcirculatesinplasma how
freelyinplasma, not bound
thus, PTHisrapidlymetabolized. Thehalf‐lifeof1‐84PTHis~4minutes.
Inadditiontotheionizedcalciumconcentration what substacnes havesignificantrolesinregulatingPTHsecretion?
calcitriol(1,25‐(OH)2D;ametaboliteofvitaminD)andphosphate both also play significant roles in regulating pTH secretionn.
1,25‐dihydroxyvitaminDor calcitriol is releasedby
renalproximal‐tubulecells
Plasma Ca2+ concentration feeds back on the parathyroid glands, whereas plasma inorganic phosphate (Pi) concentration feeds back on
osteocytes.
1,25‐dihydroxyvitaminDor
calcitriol
spontaneoushypoparathyroidismisrare in what species
dog and cat
spontaneous hypoparathyroidism may occur at almost any age but the occurrence appears to be highest in
youngadults(onetofouryearsofage).
Hypoparathyroidism presenting signs and symptoms are directly attributable to
thedecreasedconcentrationofextracellularionizedcalcium.
Therateofdecreaseintheplasmacalciumconcentrationisanimportantdeterminantinthedevelopmentofneuromuscular
manifestations.
Intheabsenceofrenalfailure,thediagnosisofhypoparathyroidismis
virtuallycertainif what are found
if hypocalcemiaandhyperphosphatemiaarefound.
After hypocalcemia and hyperphosphatemia, thediagnosisof hypoparathyroidism maybefurthersupportedby
measurementoftheplasmaPTHconcentration.
AninappropriatelylowplasmaPTHconcentrationwhilethereishypocalcemia
confirmsthediagnosis,providedthattheassayusedissensitiveenoughto
measureplasmaPTHinhealthyanimals.
Emergencytreatmentofhypocalcemic tetany,requires
slow(5–10min)
intravenousinjectionofcalcium.
Oralmaintenancetherapyof hypoparathyroridism comprisessupplementationwith
avitaminDcompoundandcalciumlactateorcarbonate.
Hypercalcemiamaybesuggestedbypolyuriaandwhenconfirmedby
measurementsofplasmacalcium,supplementationshouldbestoppedtominimizetheriskofrenalinsufficiencyduetonephrocalcinosis.
Hyperparathyroidismcanbe classed as (2)
primaryorsecondary
Primaryhyperparathyroidismis
thestateofautonomoushypersecretionofPTH,mostcommonlybyanadenomaofthechiefcells of the PTgland.
Secondaryhyperparathyroidismis
anadaptiveincreaseinPTHsecretion,unrelatedtointrinsicdiseaseoftheparathyroids.
theincreasedPTHsecretionistheresultofchronicdecreasesintheconcentrationofionizedcalciuminplasma.
there are onlytwo conditionsinwhichsecondaryhyperparathyroidismproducesclinically
significantmanifestations:
- chronicrenalfailure
- calciumdeficiencyduringgrowth
Primaryhyperparathyroidismisrare; it can be due to either…
atumour (mostlyadenomasinolderanimals,particularlydogs)ortheremaybeprimaryhyperplasia.
Primaryhyperparathyroidismleadsto
what blood dyscrasias?
hypercalcaemia/hypophosphatemia;
plus renalcalculiandmetabolic
effects;because calciuminfluxisinvolvedincellularactivityinmanytissues.
Primaryhyperparathyroidismisanuncommondiseaseof what age group
olderdogs(≥6years)andthereisnopronouncedsexpredilection.
Primaryhyperparathyroidism incatsisevenlessfrequent than in dogs,andoccursinthesameage
range (6+ years),possiblywithapredilectionfor
femalesandSiamesecats.
Primaryhyperparathyroidismcan be divided into 3 rough categoriesorstagesofpresentation:
- mild - no clinical signs. hypercalcemia is an incidental finding in routine bloods.
- form - polyuria fromdecreasedvasopressin‐
regulatedexpressionofaquaporinsinthekidneycollectingducts. - most common form - surplus of nonspecific clinical signs. weakness and lethargy.
Themainprobleminthedifferentialdiagnosisofprimaryhyperparathyroidismis
distinguishingitfromotherconditions
associatedwithhypercalcemiaandspecificallyhypercalcemiaof malignancy.
Hypercalcemia of malignancy is
a common finding typically in patients with advanced stage cancers.
Othercausesofhypercalcemiacan be e.g. (3)
hypervitaminosisD,
acute renalfailure,and
primaryhypoadrenocorticism
Moderatehypercalcemiawithnoobviousidentifiablecauseisseenregularlyin
cats.
Longhaired cats seem to be predisposed and diet history may reveal that acidifying diets have been fed.
idiopathichypercalcemiaincatsmaybeassociatedwith what type of urolithiasis?
calciumoxalateurolithiasis.
Thepresenceofhypercalcemiaisestablishedwhen
3 measurements of total and ionized plasma Ca2+ concentration reveal values exceeding the reference range.
This, in combination with normo‐ or hypophosphatemia and the
appropriate signs, may give rise to the suspicion of primary hyperparathyroidism.
what type of hypercalcemia is more common than hypercalcemia of PTorigin?
hypercalcemia of malignancy
Definitedifferentiationbetweenparathyroidandnonparathyroid causesof
hypercalcemiamayrelyon
measurementofplasmaPTHconcentration.
Intheabsenceofrenalfailure,anelevatedPTHlevelconfirmsthediagnosisofprimaryhyperparathyroidism.
Aseriousdiagnosticproblemmayarisewhenitissuspectedthatprimary
hyperparathyroidismiscomplicatedbyrenalfailure.
PlasmaPTHconcentrationwithinthereferencerange,occurringin
approximately70%ofdogswithprimaryhyperparathyroidism,also
confirmsthediagnosis,asinhypercalcemiaofnonparathyroid originPTH
concentrationsshouldbelowasaresultof
theinhibitoryeffectofthehigh
plasmacalciumconcentrationonPTHrelease.
treatment of choice for hyperparathyroidism?
surgical resection of abnormal parathyroid tissue
Secondary hyperparathyroidism is more common than primary.
Give 2 Examples of secondary
Nuritional secondary hyperparathyroidism
Renalsecondary hyperparathyroidism
Nuritional secondary hyperparathyroidism is usually aresult ofadiet containing
excess phosphate (inmeat or cereal)
and/or vitamin D3deficiency may also lead to secondary hyperparathyroidism and hypocalcaemia andfinally to skeletal disease
Renalsecondary hyperparathyroidism occurs inwhat situation and due to what?
chronic intrinsic renal disease (congenital or acquired)due to failure ofphosphate excretion.
Additionally there may be reduced activation ofVitD3inthe diseased kidneys taht then reduces gut absorption ofcalcium leading to hyperparathyroidism as the body attempts to return homeostasis.
hyperostotic osteodystrophy
Mineral is removed from the skeleton and replaced by immature fibrous connective tissue. Fibrous osteodystrophy is generalized throughout the skeleton but is accentuated in local areas such as the cancellous bone of the skull.
Bones of the skull are markedly thinned by the increased resorption and have a characteristic “moth-eaten” appearance radiographically. In advanced cases, the mandible can be twisted gently due to loss of osteoid and severe fibrous osteodystrophy—hence the name “rubber jaw” syndrome.
Themainstimuli inthe
pathogenesisofsecondary
hyperparathyroidismduetochronic
renalinsufficiency
1)renalretentionofphosphate,which
causesprecipitationofcalciuminsoft
tissues
(2)decreasedproductionof1,25‐(OH)2D/ calcitriol
= all equal too little calcium which triggers more and more PTH
clinical presentation of Renalsecondaryhyperparathyroidism
classicsignsofrenalinsufficiency:
* Anorexia
* Vomiting
* Polydipsia
* Polyuria
* Depression
Insomecasesthesefeaturesmaybemildoronlyintermittent.
Theskeletalchangesrangefrommildtosevereformsoffibrousosteodystrophy (loss of teeth).
Whenrenalinsufficiencydevelopsbeforematurationoftheskeleton
therepairbyproliferationofconnectivetissuemayexceedtherateof
boneresorption.Thisresultsin
anincreaseinbonevolumeandfacial
swelling.
Treatment of Renalsecondaryhyperparathyroidism
restrictionofdietaryphosphorus
Administeringaluminumcontainingantacidsthatpreventphosphateabsorption.
IncasesinwhichthereisatendencytohypocalcemiathisapproachmaybeextendedbysupplementationwithcalciumandvitaminDsterols.
what is allmeatsyndrome
seeninanimalsfedanunbalancedfoodmainlybasedonmeatormeatby‐products.
Ifinsufficientcalciumisavailableinthefood,thecalciumconcentrationinplasmawilltendtodecrease,initiatingnutritional secondary hyperparathyroidism.
Clinicalmanifestations of nutritional secondary hyperparathyroidism.
In growing dogs, especially of the larger breeds, and cats a substantial amount of calcium is laid down as calcium phosphates in newly‐formed osteoid and cartilage.
Compression fractures, partial thickness fractures and deformed skeletal protuberances.
Secretionofcalcitoninisstimulated
by?
And inhibited by?
high serum [Ca2+] and is inhibited by normal or low serum [Ca2+]
Themainroleofcalcitoninisto
inhibit bone resorption, which reduces liberation of the calcium and phosphate, thereby indirectly lowering serum Ca2+ levels.
It also prevents acute hypercalcemia due to dietary intake postprandially (after eating).
Calcitoninincreasestheurinaryexcretionof
Ca2+,PO43−,Na+,andK+and
reducestheexcretionofMg2+.
DiseaseStatesofCalcitonin
A large number of diseases are associated with abnormally increased or decreased levels of calcitonin, but pathologic effects of abnormal calcitonin secretion per se are not generally recognized.
