Physiology for General Surgical Sciences Examination (GSSE)

© Springer Nature Singapore Pte Ltd. and People's Medical Publishing House Co. Ltd. 2019

S. Ali Mirjalili (ed.)Physiology for General Surgical Sciences Examination (GSSE)https://doi.org/10.1007/978-981-13-2580-9_1

1. Endocrine and Reproductive Physiology

S. Ali Mirjalili¹  , Lucy Hinton² and Simon Richards³, ⁴

(1)

Department of Anatomy and Medical Imaging, University of Auckland, Auckland, New Zealand

(2)

Department of General Surgery, Tauranga Hospital, Tauranga, New Zealand

(3)

Department of General Surgery, University of Otago, Christchurch, New Zealand

(4)

Christchurch Hospital, Christchurch, New Zealand

S. Ali Mirjalili

Email: [email protected]

Keywords

HypothalamusPituitaryCalcium

1.1 Mechanisms of Hormonal Action

Short notes

Three main types of hormones:

1.

Steroid (Lipid soluble): Synthesised from cholesterol. Diffuse out of cell through phospholipid bi-layer. Need to be bound to plasma proteins.

2.

Peptide/Protein (Water soluble): Usually formed from a precursor, which is cleaved prior to leaving the cell. Stored in cytoplasmic granules. Released by exocytosis.

3.

Amino acid tyrosine derivatives (Water soluble): Thyroid and adrenal medulla hormones.

Function of hormones:

Hormones may act at the cell surface or diffuse into the cell to act on nuclear receptors:

Hormones may act by entering the cell surface → cytoplasmic/nuclear receptors → modify mRNAs

e.g. thyroid hormones, steroid hormones, vitamin D

Steroid hormones can diffuse (or be transported) through the cell membrane

Binding may occur in the cytoplasm or nuclear membrane

Receptor may then bind to specific parts of the DNA (serum response element or SRE) and regulate mRNA transcription

Hormones may function by acting at the cell surface

By altering ion movements (often regarded as neurotransmitters) and binding directly to ion channels

e.g. Na+ – K+, GABA/glycine – Cl−, Nicotinic Acetylcholine receptor

By ↑ or ↓ adenylate cyclase → ↑ or ↓ production of cyclic AMP (cAMP), by converting ATP to cAMP via G-proteins. cAMP binds to the regulatory subunit of a specific protein kinase

e.g. PTH, TSH, Glucagon, ACTH, Catecholamines via beta-1 receptors → ↑ cAMP

Catecholamines acting via alpha-2 →↓ cAMP

By ↑ guanylate cyclase → ↑ cGMP → e.g. ANP and NO. Similar process as above. Initial action may span the cell membrane [with intra and extracellular functions (ANP)], or act entirely intracellularly (NO)]

By activating phospholipase C → hydrolysis of cell membrane phospholipids → IP3 and diacylglycerol

IP3 → binds to ER → Ca²+ release (3rd messenger)

Diacylglycerol → ↑ protein kinase C → phosphorylates proteins and alters their function

e.g. vasopressin, TRH, angiotensin II, catecholamines via alpha receptors

By acting on tyrosine kinase → ↑ activity

Occurs by spanning membrane → activates tyrosine kinase

e.g. insulin, EGF, PDGF

By linking to intracellular tyrosine kinase

e.g. cytokines, GH

1.2 Hypothalamus and Posterior Pituitary

Questions

1.

How is thirst controlled by the hypothalamus?

By sensing changes in plasma osmolarity through osmoreceptors (anterior hypothalamus)

By sensing blood volume changes through angiotensin II

By sensing blood volume changes through baroreceptors peripherally

2.

Explain the control mechanism for release of hormones from the posterior pituitary.

Posterior pituitary hormones are synthesised by cell bodies in the hypothalamus. These cells are known as magnocellular neurons in the supraoptic and paraventricular nuclei of the hypothalamus. The pathway from the hypothalamus to the posterior pituitary is called the hypothalamo-neurohypophyseal tract. The hormones (ADH and oxytocin) are stored in vesicles, which are released following various neural stimuli.

3.

Explain the mechanism of action of ADH.

Its main action is to prevent the loss of water in the kidneys by concentrating urine.

Acts on renal collecting ducts to ↑ permeability to water passing from urine to medullary fluid (via V2 → cAMP → ↑ water channels from endosomes)

Secondary actions are;

Increases urea permeability in the collecting ducts of the inner medulla of the kidney

Vasoconstriction via V1a → G-protein → ↑ in Ca²+ → blood vessel constriction

Seen in liver, brain, kidney, mesangial cells

Stimulation of ACTH release by corticotrophins in the anterior pituitary via V1b → G-protein → Ca²+ release

Stimulation of glycogen breakdown in the liver

4.

What are the effects of oxytocin?

Contraction of myoepithelial cells in the breast → milk ejection

Contraction of smooth muscle of uterus

ADH effect in high concentrations

5.

What is diabetes insipidus?

This is a condition where the body has an abnormal inability to secrete or respond to ADH. May be due to destruction (neoplasm/trauma) of hypothalamus (neurogenic) leading to lack of ADH, or due to inability of the kidney (nephrogenic) to respond to ADH (acquired or genetic). It results in water loss through the kidneys resulting in polydipsia, polyuria (often >20 L/day) and thirst.

Short notes

Functions of the hypothalamus

1.

Control of anterior pituitary hormone secretion (via releasing hormones) see text of anterior pituitary.

2.

Control of appetite

Lateral feeding centre chronically active but suppressed by satiety centre and possibly CCK and leptin

Ventrolateral satiety centre senses glucose utilisation and is insulin sensitive

3.

Role in cyclic phenomena - circadian rhythms, body temperature

4.

Control of thirst

By sensing changes in plasma osmolarity through osmoreceptors (anterior hypothalamus)

By sensing blood volume changes through angiotensin II

By sensing blood volume changes through baroreceptors peripherally → nerves

5.

Control of posterior pituitary secretion (vasopressin/ADH, oxytocin)

Formed as preprohormones

6.

Vasopressin (ADH)

Stimulated by anti-diuretic hormone mechanisms

↑ in plasma osmotic pressure (sensed by anterior hypothalamus)

↓ in plasma volume (sensed by baroreceptors – overrides osmotic effect)

Angiotensin II

Stress and pain

Drugs (morphine, nicotine)

Sleep

Inhibited by pro-diuretic mechanisms

↓ in plasma osmotic pressure

↑ in plasma volume

Alcohol

Not bound in plasma, readily distributed, degraded by proteolysis

Actions

Antidiuretic action

Acts on collecting ducts to ↑ permeability to water passing from urine to medullary fluid (via V2 receptor→ cAMP → ↑ water channels from endosomes)

Increases urea permeability in the collecting ducts of the inner medulla of the kidney

Vasoconstriction

Via V1a receptor → G-protein → ↑ in Ca²+ → blood vessel constriction

Seen in liver, brain, kidney, mesangial cells

Stimulation of ACTH release by corticotrophins in the anterior pituitary via V1b receptor→ G-protein → Ca²+ release

Stimulation of glycogen breakdown in the liver

Diabetes insipidus

May result from destruction (neoplasm / trauma) of hypothalamus (neurogenic) leading to a lack of ADH, or due to inability of the kidney (nephrogenic) to respond to ADH (acquired or genetic)

7.

Oxytocin (hormone related to ADH)

Stimulated by mechanical vaginal distension, nipple stimulation, stress

Inhibited by Alcohol

Actions:

Contraction of myoepithelial cells in the breast → milk ejection

Contraction of smooth muscle of uterus

ADH effect in high concentrations

Effects mediated by specific receptor → G protein → Ca²+ release

Number of receptors increases dramatically during late stages of pregnancy

8.

Pineal gland

Secretes melatonin cyclically (high at night, low during the day)

1.3 Anterior Pituitary

Questions

1.

Which cells of the anterior pituitary release TSH, LH, FSH, ACTH, GH and Prolactin?

2.

What stimulates the release of GH?

Its release occurs when there is a decrease in metabolic fuels [e.g. hypoglycaemia, ketosis] as well as stress, sleep, glucagon, fasting and L-dopa.

3.

What is somatostatin?

This is a hormone, also known as growth hormone–inhibiting hormone (GHIH), which is released by the hypothalamus and inhibits release of GH.

4.

What are the direct effects of GH release?

Think of GH as increasing protein stores, decreasing fat stores and conserving carbohydrates.

Direct effects of GH include:

Carbohydrate: ↓ glucose uptake by cells, stimulates hepatic glucose output and ↑ insulin secretion.

Fat: Stimulates lipolysis and mobilisation of fatty acids from adipose tissue, ↑ conversion of fatty acids to acetyl coenzyme A

Protein: ↑ amino acid uptake, ↑ RNA translocation, ↓ catabolism of protein and amino acids.

Bone: ↑ protein deposition, ↑ cell reproduction, ↑ osteogenic cells

Stimulates erythropoiesis

5.

What are somatomedins?

Somatomedins are a group of proteins released from the liver that promote cell growth and division in response to stimulation by growth hormone (GH)

Short notes

Hormones of the Anterior Pituitary

Release is regulated by the hypothalamus

Glycoproteins are composed of an α subunit (identical) and β subunit (differs)

Please see texts for details on TSH, LH and FSH, ACTH

Growth Hormone (GH)

Does not act on a specific organ but exerts its effect directly on almost all tissues of the body.

Related structurally to prolactin

Circulates bound to carrier proteins with a t ½ of 20 min

Secretion is pulsatile

Presence of fuels inhibits secretion and vice versa

↑ by GHRH (Growth hormone releasing hormone) in response to

↓ in metabolic fuels (e.g. ketosis, hypoglycaemia), certain amino acids, stress, deep sleep, sex steroids, glucagon, exercise, fasting, ghrelin, and L-dopa.

↓ by GHIH (Growth hormone inhibitory hormone/somatostatin) in response to

Free fatty acids, glucose

IGF-I (insulin-like growth factor-I) provides negative feedback

Stimulates IGF-I production by the liver

Think of GH as increasing protein deposition, decreasing fat stores and conserving carbohydrates.

Direct effects of GH include

Carbohydrate: ↓ glucose uptake by cells, stimulates hepatic glucose output and ↑ insulin secretion.

Fat: Stimulates lipolysis and mobilisation of fatty acids from adipose tissue, ↑ conversion of fatty acids to acetyl coenzyme A

Protein: ↑ amino acid uptake, ↑ RNA translocation, ↓ catabolism of protein and amino acids.

Bone: ↑ protein deposition, ↑ cell reproduction, ↑ osteogenic cells

Stimulates erythropoiesis

Indirect effects are mediated through IGF-I (somatomedins) from the liver.

Receptor is large and stimulates intracellular kinases

Insulin like effects, glucose uptake, anti-lipolysis etc

Other family members include EGF, NGF, PDGF

Type I receptors bind IGF-I > IGF-II

Type II receptors bind IGF II > IGF I

Insulin receptors bind insulin > IGF I

Prolactin

Secreted by lactotrophs, usually under chronic inhibition via dopamine

Secretion ↑ by

Nipple stimulation, stress, pregnancy, hypoglycaemia, oestrogens, exercise

Secretion ↓ by

L-dopa, bromocriptine

Under normal negative feedback loops, t ½ of 20 min

Promotes milk secretion by the breasts

High concentrations of prolactin inhibit LH and FSH action on the gonads and can cause infertility

1.4 Adrenal Medulla

Questions

1.

What are catecholamines derived from?

The amino acid tyrosine (Fig. 1.1).

2.

Where is PNMT (phenylethanolamine-N-methyltransferase) found?

This is the enzyme that converts noradrenaline to adrenaline. It is found in the adrenal medulla and the brain.

3.

What hormone is secreted in the largest quantity from the adrenal medulla?

Adrenaline. Converted from noradrenaline by the enzyme PNMT (phenylethanolamine-N-methyltransferase). Chromaffin cells