Endocrinology and Neurophysiology Review

Comprehensive flashcards generated from 5 lecture topics covering the Thyroid Gland, Adrenal Cortex and Medulla, Parathyroid Gland, Pancreas, and Cell Excitability.

Where is the thyroid gland anatomically located, and what is the etymological origin of its name?

The thyroid gland lies adjacent to the trachea, immediately below the larynx. It is named for its resemblance to thyroid cartilage, originating from the Greek thyr (meaning shield) and oid (meaning similar).

What are the two principal hormones synthesized by the thyroid gland, and how do their chemical structures differ?

The two principal hormones are thyroxine ($T_4$, or 3, 5, 3', 5'-tetraiodothyronine) and triiodothyronine ($T_3$, or 3, 5, 3'-triiodothyronine). They differ solely in the number of iodine atoms bound to the molecule ($4$ versus $3$).

What are the five sequential steps in thyroid hormone synthesis and secretion within follicular cells?

1) Follicular cells absorb iodide ions ($I^-$) from the blood; 2) Follicular cells synthesize thyroglobulin (a large protein containing over $100$ tyrosine residues); 3) Iodide ions are added to tyrosine residues on the surface of thyroglobulin; 4) TSH stimulates follicular cells to absorb thyroglobulin droplets, which lysosomes hydrolyze to release thyroid hormone; 5) Thyroid hormone is secreted into nearby capillaries to combine with plasma proteins.

What five cellular changes occur in the thyroid gland in response to Thyroid Stimulating Hormone (TSH)?

1) Increased proteolysis of stored thyroglobulin; 2) Increased activity of the iodide pump ("iodide trapping"); 3) Increased iodination of tyrosine; 4) Increased size and secretory activity of thyroid cells; 5) Increased number of thyroid cells, accompanying a shape change from cuboidal to columnar epithelium.

How are $T_4$ and $T_3$ transported in plasma, and what percentages exist as free hormone?

Both hormones travel bound to plasma proteins, including thyroid-binding globulin (TBG), transthyretin (TTR), and albumin. For $T_4$, $99.98\%$ is protein-bound and $0.02\%$ is free; for $T_3$, $99.70\%$ is protein-bound and $0.30\%$ is free.

In an animal presenting with low TSH and low $T_3/T_4$, how does a TRH stimulation test differentiate a hypothalamic defect from a pituitary defect?

If the defect is at the hypothalamus, administering TRH will cause an increase in plasma TSH and an increase in plasma $T_3/T_4$. If the defect is at the anterior pituitary, TRH administration will result in no change in plasma TSH or $T_3/T_4$.

What mechanism causes endemic goiter in iodine-deficient conditions?

Without iodine, the thyroid gland cannot synthesize thyroid hormone. Lacking negative feedback from thyroid hormone, the anterior pituitary secretes excess TSH, which causes the thyroid gland to continuously produce thyroglobulin, leading to colloid accumulation and gland enlargement.

What are the three histological zones of the adrenal cortex and the primary hormone class secreted by each?

1) Zona glomerulosa secretes aldosterone (mineralocorticoid); 2) Zona fasciculata secretes cortisol (glucocorticoid); 3) Zona reticularis secretes androgens (sex steroids like DHEA).

What is the common precursor molecule for all steroid hormones synthesized in the adrenal cortex?

Cholesterol is the precursor molecule for all steroid hormones.

Through what intracellular pathway does ACTH stimulate acute cortisol release in the zona fasciculata?

ACTH binds to high-affinity cell surface receptors, activating $G_s$ and adenylate cyclase to increase intracellular $\text{cAMP}$. This activates protein kinase A (PKA), triggering immediate release of cortisol and synthesis of steroidogenic enzymes.

What five specific actions enable cortisol to prevent or suppress tissue inflammation?

1) Stabilizes lysosomal membrane integrity; 2) Decreases capillary permeability; 3) Decreases white blood cell migration into inflamed areas and reduces phagocytosis; 4) Suppresses the immune system by lowering T lymphocyte and antibody production; 5) Attenuates fever by reducing interleukin-1 release from white blood cells.

What is the cellular mechanism of action of aldosterone on renal principal cells?

Aldosterone binds cytoplasmic mineralocorticoid receptors (MR) and translocates to the nucleus to induce protein synthesis, increasing the synthesis and insertion of epithelial sodium channels (ENaCs) into the apical membrane and $\text{Na}^+/\text{K}^+$ ATPase pumps into the basolateral membrane.

What sequence of enzymatic steps converts tyrosine into epinephrine in the adrenal medulla?

Tyrosine $\rightarrow$ L-Dihydroxyphenylalanine (L-Dopa) via tyrosine hydroxylase $\rightarrow$ Dopamine $\rightarrow$ Norepinephrine $\rightarrow$ Epinephrine.

How is parathyroid hormone (PTH) secretion regulated, and what is its primary stimulus?

PTH secretion from the parathyroid glands is regulated directly and solely by the plasma concentration of free $\text{Ca}^{2+}$, increasing when plasma $\text{Ca}^{2+}$ drops below normal levels.

What four direct effects does PTH exert to elevate plasma calcium concentrations?

1) Increases bone resorption by osteoclasts; 2) Directly stimulates renal $1\alpha\text{-hydroxylase}$ to form active $1,25(\text{OH})_2\text{-D}$; 3) Increases renal tubular calcium reabsorption; 4) Decreases renal tubular phosphate reabsorption (promoting phosphate excretion).

How is Vitamin D converted into its fully active form, calcitriol?

Pro-Vitamin D ($7\text{-dehydrocholesterol}$) in skin is converted by UV light to cholecalciferol, undergoes $25\text{-hydroxylation}$ in the liver to $25(\text{OH})\text{D}_3$, and undergoes $1\alpha\text{-hydroxylation}$ in the kidney to form active $1,25(\text{OH})_2\text{-D}$ (calcitriol).

Where is calcitonin synthesized, and what stimulus triggers its release?

Calcitonin is a $32\text{-amino acid}$ peptide synthesized by parafollicular cells (C cells) of the thyroid gland in response to elevated plasma calcium concentrations.

What are the three main endocrine cell types in pancreatic islets, their relative abundances, and their secreted products?

1) Beta ($\beta$) cells ($\sim 60\%$, secrete insulin); 2) Alpha ($\alpha$) cells ($\sim 30\%$, secrete glucagon); 3) Delta ($\delta$) cells ($< 10\%$, secrete somatostatin).

Why are pancreatic islet hormone concentrations significantly higher in the liver than in systemic circulation?

Blood draining the microcirculation of pancreatic islets enters the hepatic portal vein, delivering hormones directly to the liver before they enter general circulation.

What enzyme acts as the pancreatic $\beta\text{-cell}$ glucose sensor, and what reaction does it catalyze?

Glucokinase acts as the glucose sensor by catalyzing the first, rate-limiting step of glycolysis: the phosphorylation of glucose to glucose-6-phosphate.

What sequence of cellular events leads to insulin exocytosis in pancreatic $\beta$ cells upon glucose entry?

Glucose entry via GLUT transporters $\rightarrow$ Glucokinase-mediated glycolysis $\rightarrow$ Increased ATP production $\rightarrow$ Closure of ATP-sensitive $\text{K}^+$ channels $\rightarrow$ Membrane depolarization $\rightarrow$ Opening of voltage-gated $\text{Ca}^{2+}$ channels $\rightarrow$ $\text{Ca}^{2+}$ influx $\rightarrow$ Exocytosis of insulin granules.

Why is C-peptide useful as a diagnostic marker for endogenous insulin production?

C-peptide is cleaved from proinsulin and secreted in equimolar amounts with insulin. Unlike insulin (which has a half-life of $3\text{--}5\text{ minutes}$ and is cleared by the liver and kidneys), C-peptide is cleared exclusively by the kidneys and has a half-life $3$ to $4$ times longer.

What therapeutic actions do GLP-1 receptor agonists (incretins) exert in managing Type 2 Diabetes?

GLP-1 receptor agonists amplify glucose-stimulated insulin release from pancreatic $\beta$ cells, slow gastric emptying, and suppress glucagon secretion from $\alpha$ cells.

What are the standard extracellular (ECF) versus intracellular (ICF) concentrations of $\text{Na}^+$, $\text{K}^+$, and $\text{Cl}^-$ in mammalian resting cells?

Extracellular (ECF): $\text{Na}^+ = 142\,\text{mM}$, $\text{K}^+ = 4\,\text{mM}$, $\text{Cl}^- = 110\,\text{mM}$. Intracellular (ICF): $\text{Na}^+ = 14\,\text{mM}$, $\text{K}^+ = 140\,\text{mM}$, $\text{Cl}^- = 10\,\text{mM}$.

What formula defines the Nernst Equation for calculating an ion's equilibrium potential at $37^\circ\text{C}$?

$$E_{\text{ion}} = \frac{61.0\,\text{mV}}{z} \log_{10}\left(\frac{[\text{Ion}]_{\text{out}}}{[\text{Ion}]_{\text{in}}}\right)$$

What are the calculated Nernst equilibrium potentials for $\text{K}^+$ ($E_{\text{K}}$) and $\text{Na}^+$ ($E_{\text{Na}}$) under physiological conditions?

The equilibrium potential for potassium ($E_{\text{K}}$) is $-94\,\text{mV}$ ($[\text{K}]_{\text{out}} = 4\,\text{mM}, [\text{K}]_{\text{in}} = 140\,\text{mM}$), and for sodium ($E_{\text{Na}}$) is $+62\,\text{mV}$ ($[\text{Na}]_{\text{out}} = 142\,\text{mM}, [\text{Na}]_{\text{in}} = 14\,\text{mM}$).

How does the $\text{Na}^+/\text{K}^+$ ATPase pump electrogenically influence the resting membrane potential?

The pump actively transports $3\,\text{Na}^+$ ions outward for every $2\,\text{K}^+$ ions inward, creating a net deficit of positive charges inside the cell that contributes approximately $-4\,\text{mV}$ to the resting membrane potential.

What genetic and physiological defect causes Myotonia Congenita in myotonic goats and affected cats?

A point mutation in the skeletal muscle chloride channel gene (CLCN1) reduces resting $\text{Cl}^-$ conductance, resulting in membrane hyperexcitability and delayed muscle relaxation following voluntary contraction.