Endocrine & Metabolic Physiology

Metabolic actions of glucocorticoids Effects On carbohydrate  -Promotion of gluconeogenesis
Metabolism - (cortisol stimulates synthesis of gluconeogenic enzyme by DNA transcription)
-  Reduction in glucose utilization
-  Increase deposition of liver glycogen
-Block glucose transport in muscle and
-Adipose tissue (anti insulin action)
Net effect: increased blood glucose

The kidneys synthesize glucose from amino acids and other precursors during prolonged fasting, a process referred to as gluconeogenesis. The kidneys’ capacity to add glucose to the blood during prolonged periods of fasting rivals that of the liver.

TSH is most sensitive thyroid function test.

Laboratory findings in Conn's syndrome:
1.  Urinary potassium excretion increases
2.  Increased plasma aldosterone with decreased plasma renin concentration.
3.  Urinary aldosterone excretion increases.
4.  Hypokalemia.

 Nonspecific laboratory findings associated with hyperthyroidism

Ø  Decreased serum cholesterol, LDL-C & TAG.

Ø  Increased CPK (due to myopathy)

Ø  Hepatic dysfunction, e.g. raised ALT and ALP

Metabolic features:
1.  Dilutional hyponatremia, hyperkalemia and metabolic acidosis.
2.  Marked insulin sensitivity and hypoglycemia.
3.  Renal salt and water loss, hypotension & weight loss.
4.  Hyperpigmentation of skin and buccal mucosa (due to increased ACTH following decreased cortisol).
5.  Adrenal crisis (Addisonian crisis)
It is the state of acute adrenocortical insufficiency in patients with Addison’s disease who are exposed to the stressful conditions like infection, trauma surgery, vomiting, diarrhoea etc. Patients become confused, disoriented and eventually develop severe hypotension and shock.

Ref: ABC 6th/P-510

 Functions of ACTH:
1.  Growth of adrenal cortex.
2.  Stimulation of glucocorticoid secretion.
3.  Mild stimulation of adrenal androgen secretion.
4.Stimulates melanocytes and causes skin pigmentation

Hormones that counteract the action of insulin Diabetogenic hormones:
1.  Glucagon
2.  Cortisol
3.  Epinephrine & Norepinephrine
4.  Growth hormone
5.  Thyroid hormone

Explanation-
★ The insulin receptor in target tissues is a tetramer. The two β subunits have tyrosine kinase activity and autophosphorylate the receptor when stimulated by insulin.
Reference-Ganong physiology/26th/P-424 &BRS physiology/6th/P-249/Fig-7.3

Composition of HDL
Apoprotein 50 %
Apo A
Apo C
Apo E

Lipid 50%


ABC of Biochemistry 6th - P: 218

Vasopressin:
Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg- GlyNH2
Oxytocin:
Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-GlyNH2 

Stress management (fight & flight response to face sudden emergency) by:
Ø  Gluconeogenesis that provides glucose to be used as fuel in neurons.
Ø  Proteolysis that provides amino acid to support gluconeogenesis and acute phase protein synthesis in liver.
Ø  Lipolysis that provides fatty acid to be used as fuel in peripheral tissues.
Ø  Maintenance of ECF volume and blood pressure.

* For these functions in relation to stress, cortisol is called emergency hormone

Anterior pituitary is also known as the master gland because it regulates many other endocrine glands through its hormones.

Cortisol has permissive action on glucagon & catecholamine

TSH, also known as thyrotropin, is an anterior pituitary hormone; it is a glycoprotein with a molecular weight of about 28,000. This hormone increases secretion of thyroxine and triiodothyronine by the thyroid gland. It has the following specific effects on the thyroid gland:
1. Increased proteolysis of thyroglobulin that has already been stored in the follicles, releasing the thyroid hormones into the circulating blood and diminishing the follicular substance
2. Increased activity of the iodide pump, which increases the rate of "iodide trapping" in the glandular cells, sometimes increasing the ratio of intracellular to extracellular iodide concentration in the glandu- lar substance to as much as eight times normal
3. Increased iodination of tyrosine to form the thyroid hormones
4. Increased size and increased secretory activity of the thyroid cells
5. Increased number of thyroid cells plus a change from cuboidal to columnar cells and much infolding of the thyroid epithelium into the follicles
In summary, TSH increases all the known secretory activities of the thyroid glandular cells.

The most important early effect after administration of TSH is to initiate proteolysis of thyroglobulin, which causes release of thyroxine and triiodothyronine into the blood within 30 minutes. The other effects require hours or even days and weeks to develop fully.

Both T4 & T3 are mostly bound to thyroxine binding Globulin (TBG)

With renin low and aldosterone high (primary hyperaldosteronism)
·         Adrenal adenoma secreting aldosterone (Conn's syndrome)
·         Idiopathic bilateral adrenal hyperplasia
·         Glucocorticoid-suppressible hyperaldosteronism (rare)

Myxedema can be diagnosed over telephone by hearing frog like husky voice.

[Guyton 13th 7]

Insulin causes hypoglycemia by:
1.  Uptakes & oxidation of glucose by cells
2.  Uptake & storage of glucose as glycogen in muscle & liver.
3.  Uptake & utilization of glucose for lipogenesis & fat synthesis in adipocyte.
4.  Inhibition of gluconeogenesis & glycogenolysis

Others are secreted from follicular cell

Hypoparathyroidism leads to hypocalcemia, by decreasing the resorption of calcium from bones. Hypocalcemia causes neuromuscular hyperexcitability, resulting in hypocalcemic tetany. Normally, tetany occurs when plasma calcium level falls below 6 mg/dL from its normal value of 9.4 mg/dL.

Melatonin is secreted from pineal gland

Explanation-
★Ca2+ deficiency (low Ca2+ diet or hypocalcemia) activates 1α-hydroxylase, which catalyzes the conversion of vitamin D to its active form, 1,25-dihydroxycholecalciferol. Increased parathyroid hormone (PTH) and hypophosphatemia also stimulate the enzyme. Chronic renal failure is associated with a constellation of bone diseases, including osteomalacia caused by failure of the diseased renal tissue to produce the active form of vitamin D.
Reference-Vision physiology/9th/P-366/Fig-10.36 & BRS physiology/6th/P-254/Fig-7.14

All other are diabetogenic

Other three are catecholamines only.

Calcitonin is secreted from parafollicular cell

Following are the clinical indications for performing the Ghrelin Blood Test:
1. Gastric bypass surgery.
2. Monitoring obesity.
3. Rapid weight loss or weight gain.
4. Suspected anorexia nervosa

Explanation-
★ Growth hormone is secreted in pulsatile fashion, with a large burst occurring during deep sleep (sleep stage 3 or 4). Growth hormone secretion is increased by sleep, stress, puberty, starvation, and hypoglycemia. Somatomedins are generated when growth hormone acts on its target tissues; they inhibit growth hormone secretion by the anterior pituitary, both directly and indirectly (by stimulating somatostatin release).
Reference-Guyton & Hall/13rd/P-927 & BRS physiology/6th/P-234

In Addison’s disease there is hyposecretion of cortisol.

Cortisol is stress hormone

Ghrelin is released by the stomach.

Phaeochromocytoma is a catecholamine secreting tumor.

a₁-antitrypsin deficiency is an autosomal recessive disorder (C), which results from single amino acid substitutions at positions 264 and 342 on chromosome 14. ₁-antitrypsin is a serine protease, synthesized in the liver, required in controlling inflammatory cascades. The lack of this serine protease results in emphysema (75 per cent), chronic liver disease and hepatocellular carcinoma, asthma, pancreatitis, gallstones, Wegener's granulomatosis.
Patients with liver disease secondary to d₁-antitrypsin deficiency usually present with dyspnoea (from emphysema), liver cirrhosis, cholestatic jaundice. Investigations include: serum a₁-antitrypsin levels, liver biopsy, genetic phenotyping and DNA analysis at prenatal diagnosis. Management involves quitting smoking, augmentation therapy with α₁-antitrypsin pooled from human plasma and liver transplantation is the treatment of choice in decompensated cirrhosis.

Graves’ disease
Definition: It is an autoimmune disease in which circulating antibodies are formed against the TSH receptor and activates the thyroid gland hyperactive, resulting in development of goiter and hypersecretion of T3 & T4
More common in women

Clinical features:
1.  Goiter with bruit
2.  Exophthalmos-protrusion of the eye ball (it is the hallmark of Graves' disease)
3.  Retraction of upper eye lid, lid lag
4.  Corneal ulceration
5.  Diplopia
6.  Ophthalmoplegia
7.  Papilledema
8.  Loss of visual acuity
9.  Vitiligo
10.  Digital clubbing
11.  Pretibial myxedema

 

  Nonspecific laboratory findings associated with hypothyroidism.
Ø  Increased serum total cholesterol and LDL-C

Ø  Increased TAG (Triacyl glycerol)

Ø  Hyponatremia (due to free water retention)

Ø  Increased CPK (due to myopathy)

How to perform an oral glucose tolerance test (OGTT)
Preparation before the test
·       Unrestricted carbohydrate diet for 3 days
·       Fasted overnight for at least 8 hrs
·       Rest for 30 mins
·       Remain seated for the duration of the test, with no smoking

The Permissive action of cortisol is on glucagon

Aldosterone is life saving hormone

Insulin & GH directly control cellular function

Glucose is the only fuel used by brain.

Factor favour RCT
1. HDL receptors on peripheral tissue /hepatocytes
2. Apo A
3. LCAT
4. CETP
5. HL

ABC of Biochemistry 6th - P: 221