ENDOCRINE PHYSIOLOGY FOR ANESTHESIA.

1. Endocrine physiology
DR.IBRAHIM HASSAAN, MBChB,MSC,EDAIC
07/07/2023

2. Thyroid gland

3. Thyroxine synthesized
• The thyroid gland is made up of multiple follicles
• spheres of follicular cells surrounding a core of thyroglobulin, a large
protein containing many tyrosine residues.

4. • T3 and T4 are synthesized as follows
• Iodide (I‾) uptake. I‾ is actively transported from, the circulation to
the follicular cells through Na+ /I‾ co-transporter.
• secondary active transport, 25% of the body’s I‾ is stored within the
thyroid. The uptake of I‾ is stimulated by thyroid-stimulating
hormone (TSH).
• I‾ diffuses through the follicular cell and into the follicular lumen

5. I‾ oxidation:
• As I‾ is relatively inert, it must be oxidised to the more reactive iodine (I2) by
thyroid peroxidase involving hydrogen peroxide (H2O2), a reaction that is
promoted by TSH.
• I2 reaction with tyrosine. Once synthesised, I2 reacts with the tyrosine residues
of the surrounding thyroglobulin protein.
iodination :
• Tyrosine may be iodinated at one or two positions, resulting in mono-
iodotyrosine (MIT) or di-iodotyrosine (DIT), respectively.
Oxidative coupling:
Two of the iodinated tyrosine molecules are then coupled together. If two DIT
molecules join, the resulting compound is T4; if MIT is coupled to DIT, the result is
T3. This oxidative coupling of tyrosine residues is promoted by TSH

6. • The end result of this process is small T3 and T4
• molecules dispersed throughout the large thyroglobulin protein.
• In response toTSH, droplets of thyroglobulin are endocytosed by the
follicular cells. Within the follicular cell, T3 and T4 are separated from
thyroglobulin and released into the circulation.

7. Thyroid hormone synthesized

8. Regulation of the plasma concentration of thyroid hormones

9. The physiological effects of triiodothyronine(T3)
• Metabolism. affects lipolysis and gluconeogenesis
• Growth and development. important in the development (CNS)
• Respiratory system. In hyperthyroidism, increase in BMR
• Cardiovascular system. In hyperthyroidism, T3 increases the number of β-
adrenergic receptors in the heart. The result is an increase in (HR) and COP
• CNS. in hypothyroidism, depression and psychosis may occur, whilst
hyperthyroidism is associated with anxiety.
• Musculoskeletal system. In hyperthyroidism, T3 induces protein catabolism,
which predominantly affects proximal muscles, resulting in proximal
myopathy.

11. Calcium homeostasis

12. Regulation of plasma calcium concentration
Three hormones are involved in Ca2+ homeostasis.
• Parathyroid hormone (PTH) act to increase plasma Ca2 concentration
• vitamin D act to increase plasma Ca2+ concentration
• calcitonin acts to decrease plasma Ca2+ concentration

13. Parathyroid hormone
• PTH is a protein hormone secreted by the parathyroid glands ( By the
chief cells).
• There are usually four parathyroid glands, located on the posterior
surface of the thyroid gland
• Plasma Ca2+ concentration is sensed by parathyroid Ca2+- sensing
receptors .

14. Low plasma Ca2+ triggers PTH secretion, which acts at:
The kidney.
Here, it increases Ca2+ reabsorption and decreases phosphate reabsorption
Bone.
Here, it increases the activity of osteoclast cells (the cells that resorb bone),
releasing stored Ca2+
The intestine.
This is an indirect effect: PTH upregulates the renal enzyme 1-α-hydroxylase,
which is responsible for activating vitamin D (see below). Vitamin D increases
the intestinal absorption of dietary Ca2+ and phosphate.

15. Vitamin D
increases plasma Ca2+ concentration through its actions on:
The intestine, where the absorption of dietary Ca2+ and phosphate is
increased.
The kidney, where Ca2+ and phosphate reabsorption is increased.
The bone, where it increases bone calcification.

16. Calcitonin
is a peptide hormone secreted by the parafollicular C cells of the thyroid
gland.
Calcitonin has a minor role in Ca2+ homeostasis in humans, only being
secreted when plasma Ca2+ rises above 2.4 mmol/L.
Calcitonin decreases plasma Ca2+ concentration through its actions on:
The intestine, where it decreases the absorption of dietary Ca2+ and phosphate
The kidney, where it decreases the reabsorption of Ca2+ and phosphate
Bone, where osteoclast activity is decreased, thereby decreasing bone resorption

17. Parathyroidism disorders

18. Calcium

19. • The serum calcium concentration must be interpreted in relation
to serum albumin.
• Serum calcium exists in an ionised form (∼50%) or is bound to
albumin or other ions. Only ionised calcium is biologically
important.
• Various factors alter the ratio of ionised calcium to bound calcium,
but the most important factor is the albumin concentration.
• Serum calcium concentrations are therefore “corrected” to a
reference albumin concentration of 40 g/l, and for every 1 g/l of
albumin above or below this value, the calcium is adjusted by
decreasing or increasing by 0.02 mmol/l.

20. For example:
a calcium concentration of 2.05 mmol/l with an albumin concentration
of 35 g/l would be corrected to 2.15 mmol/l, which would correct the
hypocalcaemic value to normal.

21. High plasma ionised Ca2+ concentration:
– Decreases PTH secretion and, in turn, decreases the rate of activation
of vitamin D. In addition, the parafollicular C cells release calcitonin.
– The combined effect of reduced PTH, reduced vitamin D and
increased calcitonin results in a decrease in intestinal Ca2+ absorption
and renal Ca2+ reabsorption

22. Low plasma ionised Ca2+ concentration:
• Increases parathyroid PTH secretion, which, in turn, increases the rate
of vitamin D activation.
• The combined effects of vitamin D and PTH increase intestinal
absorption and renal reabsorption of Ca2+.
• The effect on bone is negligible, as the increase in bone resorption by
PTH is cancelled out by the bone calcification effect of vitamin D.

23. HYPERCALCAEMIA
• Usually become apparent when total (ionised and unionised) plasma levels
>3.5mmol/L (normal range 2.2–2.6mmol/L) or the ionised fraction
>1.7mmol/L (normal range 1.05–1.25).
• Primary hyperparathyroidism is the most common cause of mild to
moderate hypercalcaemia.
• Malignancy accounts for 50% of severe hypercalcaemia and is usually
apparent with physical examination, CXR and breast examination

24. Causes
PTH-dependent
• Primary hyperparathyroidism (the most common cause of mild hypercalcaemia).
• Tertiary hyperparathyroidism (in the context of chronic kidney disease).
• Familial hypocalciuric hypercalcaemia (slightly raised PTH).
PTH-independent
• Myeloma.
• Solid tumours: breast, bronchus, kidney, lymphoma.
• Vitamin D excess (especially the 1 alpha analogues of vitamin D).
• Sarcoidosis.
• Thyrotoxicosis.

25. Hypercalcaemic crisis
Serum calcium >4.5mmol/L is life-threatening
• Rehydrate (4–6L of fluid often required)
• Bisphosphonates are potent inhibitors of osteoclastic bone resorption
• Calcitonin decrease in skeletal release of calcium and phosphate
• 2nd-line treatment, once volume repletion has been achieved, is with
forced saline diuresis with furosemide (40mg IV every 4hr).
• Hydrocortisone (200–400mg IV daily) in patients with malignancy.
• Dialysis is reserved for patients with renal failure.

26. ionized hypocalcemia
• The treatment of ionized hypocalcemia should be directed at the
underlying cause of the problem. Calcium replacement should be
reserved only for symptomatic hypocalcemia, which is uncommon.
• Calcium Replacement Therapy

27. The adrenal glands
anatomy
The adrenal glands are triangular organs closely related to the superior
poles of the kidneys at the level of the T12 vertebral body.
blood supply:
via three main arteries:
1. Superior adrenal artery – arises from the inferior phrenic artery.
2. Middle adrenal artery – arises from the abdominal aorta.
3. Inferior adrenal artery – arises from the renal arteries.

28. The adrenal gland consists of two distinct parts that differ in their
embryological origins:
The (outer) adrenal cortex
makes up 70% of the adrenal glands’ weight.
The adrenal cortex is composed of three layers:3
– Zona glomerulosa, the outermost layer, is the main site of aldosterone
production.
– Zona fasciculata, the middle layer, is the main site of glucocorticoid synthesis.
– Zona reticularis, the inner layer, produces androgens.

29. • The (inner) adrenal medulla
innervated by T5–T9 pre-ganglionic sympathetic neurons; the adrenal
medulla can be considered to be a modified sympathetic ganglion.
Sympathetic nervous system activity stimulates the chromaffin cells to
release granules containing adrenaline (approximately 80%) and
noradrenaline (approximately 20%).

30. common types of adrenal disorders
• Addison’s disease, also called adrenal insufficiency. In this disorder, you don’t
produce enough cortisol and/or aldosterone.
• Cushing’s syndrome. In this disorder, your levels of cortisol are too high. This
term can be applied when large doses of steroids are given to treat certain
medical conditions.
• Congenital adrenal hyperplasia. This term refers to genetic condition in which
your adrenal glands are not able to make cortisol well. As a result ACTH is
elevated.
• Adrenal gland suppression. This is a type of adrenal insufficiency that is related
to outside sources of cortisol or related synthetic hormones such as prednisone
or dexamethasone.
• Hyperaldosteronism. If you have this condition, your body produces too much
aldosterone which can lead to blood pressure elevation and potassium loss.
• Pheochromocytoma. If you have this condition, your glands make too much
epinephrine and norepinephrine which can raise blood pressure or make your
heart race.