Parathyroid Glands Histology Anatomy & Physiology Diseases.
-
Upload
camron-manning -
Category
Documents
-
view
226 -
download
2
Transcript of Parathyroid Glands Histology Anatomy & Physiology Diseases.
ParathyroidGlands
HistologyAnatomy & Physiology
Diseases
Histology
• 50/50 parenchymal cells, stromal fat
• Composed mostly of chief cells and oxyphil cells within adipose stroma (fat)
• Oxyphil cells: derived from chief cells and increase as one ages
• Both types make Parathyroid hormone
Anatomy
• Superior glands usually imbedded in fat on posterior surface of middle or upper portion of thyroid lobe
• Inferior glands near the lower part of thyroid gland
• Most of blood supply from branches of inferior thyroid artery, although branches from superior thyroid supply at least 20% of upper glands.
• Glands drain ipsillaterally by superior, middle, and inferior thyroid veins.
Parathyroid
Parathyroid Glands (posterior view of thyroid)
Parathyroid Glands are located on the posterior aspect of the thyroid; sometimes the tissue is embedded within thyroid tissue.
Parathyroid
Anatomy & Physiology
Usually four – two on each side (2-8 is normal) Parathyroid glands
1. Yellow-brown
2. oval or lentiform structures
3. weigh ~ 50 mg each
4. Measure 3-10 mm x 2-6 mm x 1-4 mm
• Lie on the posterior surface of thyroid
• May be embedded within thyroid gland
• Regulate calcium/phosphate levels
• Required for life
Parathyroid Hormone
• Synthesized in chief cells as large precursor – pre-proparathyroid hormone
• Cleaved intracellularly into proparathyroid hormone then to final 84 AA PTH
• PTH then metabolized by liver into hormonally active N-term and inactive C-term
Calcium Homeostasis
• The parathyroid cells rely on a G-protein-coupled membrane receptor designated the calcium-sensing receptor (CASR), to regulate PTH secretion by sensing extracellular calcium levels
• PTH secretion also is stimulated by low levels of 1,25-dihydroxy vitamin D, catecholamines, and hypomagnesemia.
Calcium Homeostasis
• PTH is synthesized in the parathyroid gland as a precursor hormone,preproparathyroid hormone, which is cleaved first to proparathyroid hormone and then to the final 84-amino-acid PTH.
• Secreted PTH has a half-life of 2 to 4 minutes. In the liver, PTH is metabolized into the active N-terminal component and the relatively inactive C-terminal fraction
Calcium homeostasis
• The calcium-sensing receptor (CASR) senses fluctuations in the concentration of extracellular calcium.
• Increased PTH secretion leads to an increase in serum calcium levels by increasing bone resorption and enhancing renal calcium reabsorption.
• PTH also stimulates renal 1- Hydroxylase activity, leading to an increase in 1,25-dihydroxy vitamin D, which also exerts a negative feedback on PTH secretion
Calcium homeostasis
• PTH functions to regulate calcium levels via its actions on three target organs, the bone, kidney, and gut.
• PTH increases the resorption of bone by stimulating osteoclasts and promotes the release of calcium and phosphate into the circulation.
Calcium homeostasis
• At the kidney, PTH acts to limit calcium excretion at the distal convoluted tubule via an active transport mechanism.
• PTH also inhibits phosphate reabsorption (at the Proximal convoluted tubule) and bicarbonate reabsorption.
• PTH and hypophosphatemia also enhance 1-hydroxylation of 25-Hydroxyvitamin D, which is responsible for its indirect effect of increasing intestinal calcium absorption.
Parathyroid Diseases
• Benign adenoma a. Relatively common b. Usually results in hyperparathyroidism
• Cancers are rare a. Surgical removal gives > 90%
cure rate
Parathyroid Diseases
• Hyperparathyroidism a. Affects about 100,000 patients per year
• Primary Hyperparathyroidism: – occurs in 0.1 to 0.3% of the general
population and is more common in women (1:500) than in men (1:2000).
– Normal feedback of Ca is disturbed, causing increased production of PTH (does not depend on calcium concentration)
– Acts on bone, kidneys, small intestines
Primary Hyperparathyroidism
Epidemiology– 25/100,000 – 50,000 new cases yearly– F > M– Incidence increases w/ age– Most in > 50 years old
Etiology– Unknown cause– Ionizing radiation exposure?
Hyperparathyroidism Symptoms
• Kidney stones, painful bones, abdominal groans, psychic moans, and fatigue overtones
• Kidney stones calcium phosphate and oxalate• Osteopenia, osteoporosis, and osteitis fibrosa
cystica, is found in approximately 15% of patients with PHPT. Increased bone turnover can usually be determined by documenting an elevated blood alkaline phosphatase level.
• Peptic ulcer disease, pancreatitis• Psychiatric manifestations such as florid
psychosis, obtubdation, coma, depression, anxiety, fatigue
Hyperparathyroidism (cont.)
• Secondary Hyperparathyroidism– Defect in mineral homeostasis leading to a
compensatory increase in parathyroid gland function
• Tertiary Hyperparathyroidism– After prolonged over-compensatory
stimulation, hyperplastic gland develops autonomous function
Hyperparathyroidism
• Hypercalcemia can be from other sources. Intact PTH measurement and elevated PTH level very sensitive for hyperparathyroidism
Hypercalcemia – Etimology
• Hyperparathyroidism (most common)• Malignancy (most common in hospitalized)
– Lytic metastases to bone – PTHrP producer
• Sarcoidosis / granulomatous disease• Hyperthyroidism• Familial hypocalciuric hypercalcemia
Renal Complications
• Generally the most severe clinical manifestations
• Calcium phosphate or Calcium oxalate• Severe renal damage
• Hypertension secondary to renal impairment
Bone Disease
• Osteitis fibrosa cystica– Generalized skeletal demineralization due
to an increased rate of bone destruction resulting from hyperparathyroidism
– In early descriptions of disease, many had severe bone disease (50-90%), but now 5-15%
– Subperiosteal resorption – pathognomonic of hyperparathyroidism
Generalized skeletal demineralization due to an increased rate of bone destruction resulting from hyperparathyroidism
Gastrointestinal Manifestations
• Peptic Ulcer disease • Pancreatitis • Cholelithiasis – 25-35%
Emotional Disturbances
• Hypercalcemia of any cause – assoc w/ neurologic or psychiatric disturbances– Depression, anxiety, psychosis, coma
• Severe disturbances not usually correctable by parathyroidectomy
Articular and Soft Tissue
• Chondrocalcinosis and Pseudogout 3-7%
• Deposits of Calcium pyrophosphate in articular cartilages and menisci
• Vascular and Cardiac calcifications
Neuromuscular complications
• Muscular weakness, fatigue• More commonly in proximal muscles• Sensory abnormalities also possible
Hyperparathyroid Crisis
• Most patents w/ hyperparathyroidism chronically ill w/ renal and skeletal abnormalities
• Rarely can become acutely ill• Rapidly developing weakness, N/V, weight
loss, fatigue, drowsiness, confusion, Azotemia
• Uncontrolled PTH production, hyperCa, polyuria, dehydration, reduced renal function, worsening hyperCa
Hyperparathyroid Crisis
• Definitive therapy - resection • Must reverse hyperCa first
– Diuresis - Saline hydration then Lasix to excrete Ca
– Calcitonin - rapid affect, inhibits bone resorption
– Steroids - take up to a week– Mithramycin - rapidly inhibiting bone
resorption
Treatment
• Only Curative treatment - Parathyroidectomy
• Who should have surgery? – Many found incidentally, during routine
physicals
Who should have surgery?
• NIH Consensus statement 1991• All symptomatic• If Assymptomatic
– Markedly elevated serum Ca– H/o episode life-threatening hypercalcemia– Reduce renal function– Kidney stone on Radiograph– Markedly elevated urinary Ca excretion– Substantially reduce bone mass
Standard Neck Exploration
Parathyroidectomy
• Must find all four glands• Intraoperative frozen section, PTH
measurement useful• If single gland enlarged, removal usually
curative• If multiple glands enlarged, removed. Normal
just biopsied• If all 4 enlarged (generalized parathyroid
hyperplasia) - subtotal (3 1/2 removed)– Can reimplant into forearm muscle
• Superior parathyroid• easier to find• more consistent position• just on dorsal surface of
upper thyroid• careful for superior
thyroid artery and superior laryngeal nerve
• Inferior gland• less consistent
location• may be near thymus
or inside thyroid• careful for recurrent
laryngeal nerve betw trachea / esophagus
• inferior thyroid artery
Success of Surgery
• 95% of cases cured at initial neck exploration• If failed intial procedure, can try to localize w/
Radionuclide, detect w/ gamma probe– Sestamibi concentrates in parathyroid
tissue– Increasingly used in initial operation– limits dissection– Limits operative time
• May need mediastinoscopy