Nature Reviews Flashcards
How does T3 elicit its effect?
Most biological activities of thyroid hormone are mediated by binding of T3 to the nuclear T3 receptors (TRs), which bind to thyroid response elements (TREs) in thyroid hormone-responsive genes and modulate their expression.
The two thyroid receptor genes THRA and THRB encode thyroid hormone receptor-α (TRα; also known as THRα) and TRβ (also known as THRβ), respectively. Alternative splicing and different promoter usage results in the production of three THRα and three THRβ isoforms, of which TRα1, TRβ1 and TRβ2 bind to T3.
TRα1 and TRβ1 are ubiquitously expressed, TRα1 preferentially in brain, heart, and bone and TRβ1 preferentially in liver, kidney and thyroid. TRβ2 has a more restricted expression pattern but is the predominant isoform expressed in the pituitary gland and is thereby essential for the negative regulation of TSH
How is T3 converted from T4?
The thyroid gland secretes predominantly T4 and, to a lesser extent, T3, which accounts for up to only ~20% of circulating T3. The remaining T3 is produced by peripheral tissues, such as liver and skeletal muscle, by the activating enzymes type 1 and type 2 iodothyronine deiodinase (DIO1 and DIO2, respectively), which cleave an iodine atom from T4
What is the association of TPO antibodies and pregnancy?
In pregnancy, TPOAb positivity is seen in 2–17% of women and may accompany higher serum TSH levels during the first trimester.
In more than 40% of pregnant women with thyroid autoimmunity, serum fT4 concentration falls in the hypothyroid range during late pregnancy, which may complicate diagnosing overt hypothyroidism during the third trimester. This is due to inadequate maternal thyroid capacity in response to increased demands in thyroid hormone production imposed by stimulation of the thyroid by human chorionic gonadotropin, increases in TBG, and changes in placental deiodination and renal clearance of iodine during pregnancy.
The rates of miscarriages and preterm delivery are increased in pregnant women with thyroid autoimmunity. A negative association of TPOAb positivity during pregnancy with neurodevelopment of offspring has been suggested but needs to be further investigated.
What is the Wolff-Checkoff phenomenon?
The Wolff–Chaikoff effect is known as an autoregulatory phenomenon that inhibits organification in the thyroid gland, the formation of thyroid hormones inside the thyroid follicle, and the release of thyroid hormones into the bloodstream. This becomes evident secondary to elevated levels of circulating iodide. The Wolff–Chaikoff effect is an effective means of rejecting a large quantity of imbibed iodide, and therefore preventing the thyroid from synthesizing large quantities of thyroid hormone. Excess iodide transiently inhibits thyroid iodide organification.
In individuals with a normal thyroid, the gland eventually escapes from this inhibitory effect and iodide organification resumes; however, in patients with underlying autoimmune thyroid disease, the suppressive action of high iodide may persist.
The Wolff–Chaikoff effect lasts several days (around 10 days), after which it is followed by an “escape phenomenon,” which is described by resumption of normal organification of iodine and normal thyroid peroxidase function. “Escape phenomenon” is believed to occur because of decreased inorganic iodine concentration inside the thyroid follicle below a critical threshold secondary to down-regulation of sodium-iodide symporter (NIS) on the basolateral membrane of the thyroid follicular cell.
What scoring system can be utilised to determine response to treatment in Achalasia?
Eckardt score
What are the 3 subtypes of achalasia?
Three subtypes of achalasia can be distinguished on the basis of manometric assessment of oesophageal motility patterns. Achalasia type 1 is characterized by 100% failed contractions and no oesophageal pressurization; type 2 is defined as pan-oesophageal pressurization occurring with at least 20% of swallows; and type 3 is defined as the presence of premature contraction for at least 20% of the swallows with premature contraction defined as distal latency <4.5 s.
In terms of neuronal dysfunction, achalasia types 1 and 2 are both characterized by loss of ganglion cells (aganglionosis), with a gradient of more severe loss in type 1 achalasia, whereas in type 3, inhibitory neuron function is impaired without clear neuronal loss, possibly mediated by cytokine-induced alterations in gene expression.
How do the upper oesophageal sphincter and lower oesophageal sphincter coordinate during swallowing?
To initiate a swallow both sphincters open together. Peristaltic wave passes from upper sphincter to lower. The wave triggers the lower sphincter to close.
What is the cause of achalasia?
Achalasia is an autoimmune disease that affects oesophageal myenteric neurons with confirmed cell-mediated and possible antibody-mediated mechanisms.
Oesophageal biopsy samples in achalasia demonstrate myenteric plexus neurons surrounded by inflammatory cells, predominantly T cells, eosinophils, plasma cells, B cells, mast cells and macrophages6,43,44. Immunohistochemical staining indicates that the T cells are CD3+, cytotoxic CD8+ and tumour necrosis factor (TNF)-positive.
What are the 4 classes of AF?
When AF episodes terminate spontaneously or with intervention within 7 days of onset, AF is defined as paroxysmal AF.
Continuous AF sustained for at least 7 days or terminated by cardioversion (pharmaceutical or electrical cardioversion) after the seventh day is defined as persistent AF.
Continuous AF sustained for at least 12 months and in combination with a rhythm control strategy is defined as long-standing persistent AF.
In cases in which the patient and doctor decide to stop attempts to restore or maintain sinus rhythm, AF is termed permanent AF.
