Physiology

Question 1

Describe the Mechanism of action of growth hormone?

Answer 1

1 GH binds 2 receptors → homodimer →activates JAK2 → autophosphorylation →

a. Phosphorylation of protein kinase C

b. Phosphorylation of insulin receptor substrate

c. Phosphorylation of (STAT) →↑protein synthesis

Question 2

What are the effects of Growth Hormone on metabolism?

Answer 2

1. On protein metabolism: anabolic →↑size & number of cells.
   a. ↑amino acid uptake
   b. ↑ DNA transcription
   c. Protein sparing: uses fatty acid for energy
2. On carbohydrate metabolism: hyperglycemic
   a. ↓glucose uptake & utilization in skeletal and fat cells:
   b. ↑glucose production by the liver:
   * ↑ glycogenesis
3. On fat metabolism: lipolytic & ketogenic
   a. ↑lipolysis →↑fatty acid (energy source)
   b. ↑ fatty acids uptake by the liver→ fatty liver & ↑ketone bodies formation

Question 3

3. Explain the effect of growth hormone on (bone and cartilage)?

Answer 3

1. On bone and cartilage: GH stimulates growth at epiphysis indirectly via
   ➢ Stimulate release of Somatomedin by liver & Chondrocytes

Somatomedin C causes:
a. ↑division of chondrocytes
b. ↑protein deposition by chondrocyte
c. Differentiation of chondrocytes into osteogenic cells→ deposition of new bone.

Question 4

What are Factors involved in regulation of GH Secretion/ describe role of hypothalamus?

Answer 4

GH increased by: GHRH, ↓blood glucose & FFA level, Fasting, Starvation, Exercise, Stress, Protein meal (arginine AA), sex hormones

GH decreased by: GHIH (Somatostatin), ↑blood glucose & FFA level
Obesity aging, Cortisol

Question 5

5. What are the main effects of prolactin?

Answer 5

Increase milk secretion
Prevent ovulation: inhibit gonadotrophic hormones effect on ovaries
Infertility & amenorrhea during lactation

Question 6

6. What are the main factors regulating prolactin Secretion?

Answer 6

1- Hypothalamus:
a. Prolactin stimulating hormone PRH.
b. Prolactin inhibiting hormone (dopamine) →inhibition of prolactin
c. Negative feedback: Prolactin →↑ dopamine secretion →↓ prolactin secretion

2- Physiological variations: factors ↑ PRL secretion
A. Pregnancy: ↑gradually & peaks at parturition.
B. Suckling: sharp rise with each nursing.
C. Sleep: ↑at onset then persists at plateau
D. Stress→↑ secretion

Question 7

7. Give an account on renal effects of Vasopressin (ADH)?

Answer 7

A – Renal effects:

1. In tubular system:

a- Act on V2 receptors on principal cells in late DCT, collecting tubule →↑cAMP → translocation of aquaporin2 to cell membrane → ↑H2O permeability
b- ADH induces insertion of urea transporters (UT1) in medullary collecting duct →↑ flow of urea into medullary interstitium → ↑ osmolarity → ↑water reabsorption.

2. In renal vascular system:
   * Act on V3 receptors in glomerular mesangial cells →↑ VD prostaglandin E2→ antagonizes VC effect of ADH→ maintains renal perfusion.

Question 8

Mentions the extrarenal effects of Vasopressin (ADH)

Answer 8

B– Extra-renal effects:

1. In vascular system: Act on V1 receptors →↑ Ca2+ influx → VC →↑ ABP in hemorrhage (minor effect) RAAS & Sympathetic nervous systems are the primary regulators of ABP.
2. In stress: ADH & CRH are co-secreted from paraventricular nuclei→ stimulates corticotropes → ↑ACTH →↑cortisol

Question 9

Explain how vasopressin (ADH) is regulated

Answer 9

ADH increase by: high plasma osmolarity which activates stretch inactivated cation channels which causes depolarization and ADH secretion. Low blood volume triggers atrial and baroreceptors which increase ADH. Nicotine. Stress

ADH decreased by: low plasma osmolarity, hypovolemia (low ECF), Alcohol, α- adrenergic agonists

Question 10

9. What are the effects of oxytocin?

Answer 10

Functions:

1- During sexual intercourse→ orgasm

➢In males: contraction of vas deferens → ejaculation.
➢In females: contraction of myometrium followed by relaxation →↓intra uterine pressure → help semen transport

2- During labor: contraction of the uterus

3- During suckling (Milk ejection): squeezing of milk from breast alveoli

Question 11

How is oxytocin regulated?

Answer 11

Control: neurohormonal reflex

o Stimulus:
➢ Unconditioned: receptor stimulation (suckling, genital stimulation)
➢ Conditioned: higher center stimulation e.g. seeing, hearing, smelling or thinking.

o Efferent: hormonal→ release oxytocin from posterior pituitary

Question 12

Describe the mechanism of action of thyroid hormone formation?

Answer 12

1- Thyroglobulin

2- Iodide trapping (pump): active (stimulated by TSH)

A. Na+ K+ pump →↓intracellular Na+
B. Co-transporter (2nd active transport) carries Na+ & I-
C. I- : is carried against electrochemical gradients
D. Iodide trapping also occurs in: mammary, salivary glands, gastric mucosa

3- Oxidation & Iodination: peroxidase oxidize (I-)→ iodine then binds iodine to thyroglobulin → MIT & DIT

4- Release of thyroid hormones: thyroid cells ingest part of thyroglobulin by pinocytosis→
* Pinocytic vesicles merge with lysosomes
* Proteinase →release T4, T3 ,DIT ,MIT from thyroglobulin
* De-iodinase removes (I) from DIT and MIT→ iodine is recycled again

5- Storage of thyroid hormones: extra amounts stored into follicle → cover any deficient intake for (2 – 3months) as

• Iodide intake is variable
• Thyroid cells contain small amount of reserve
• Thyroid hormones are needed to be secreted daily in blood.

Question 13

11.Describe the cellular mechanism of action of thyroid hormones?

Answer 13

Regulate gene expression:

a. T3 (mainly) & T4 bind to ligand binding domain of receptor.

b. Hormone –Receptor complex stimulate DNA transcription →formation of mRNA → translation in ribosomes →formation of many proteins.

These proteins either:
* Directly: induce cellular functions, or
* Indirectly: bind to new gene→ formation of new proteins → powerful cellular functions

Question 14

12.Describe the effects of thyroid hormone on cell metabolic activity?

Answer 14

A-On mitochondria:

• ↑size & number →↑ATP formation
• Excessive ↑in thyroid hormones → mitochondrial swelling &↑ uncoupling of oxidative phosphorylation →smaller ↑in ATP & a greater loss of heat.

B- On ions transport: ↑ Na+ K+ ATPase activity →↑ Na & K transport & ↑energy consumption.

Question 15

13.What are the effects of thyroid hormones on body metabolic processes?

Answer 15

A. On CHO metabolism:
* ↑glucose absorption, ↑insulin secretion, ↑glucose uptake by the cell,
* ↑ glycolysis & gluconeogenesis

B. On fat metabolism:
* ↑lipolysis→ ↑FFA oxidation
* ↓plasma cholesterol & ↑its secretion in bile via ↑LDL receptors on liver

C. On protein metabolism: anabolic

D. On BMR (40Calories / hr / m2 ) & normal body weight &appetite: necessary

Question 16

14.Describe the effects of thyroid hormone on growth?

Answer 16

1.Mental growth & development of brain: in fetal & first few years of postnatal life→ induces neuronal, axonal & nerves ending formation.

2. Skeletal growth
3. Sexual growth: together with sex hormones

Question 17

15.Describe the effects of thyroid hormone on body systems?

Answer 17

1. Primary effect: majority of systems are stimulated by a direct hormonal action.
2. Secondary effect: many systems are stimulated by ↑metabolism (calorigenic action)

O2 consumption increase in CVS, Res, GIT
O2 consumption is decreased in anterior pituitary

Question 18

16.Give an account on Regulation of Thyroid function?

Answer 18

1. Hypothalamus: TRH →bind G proteins on anterior
   pituitary thyrotropes→ activates PLC → ↑intracellular Ca2+ → ↑TSH release
2. TSH: binds G proteins receptors on thyroid cells → activation of ACE →↑cAMP → activates kinase → phosphorylation in thyroid cells

A. Within 30 min: ↑proteolysis of thyroglobulin→↑T3 &T4 in blood.

B. Within hours, days, and weeks:
* ↑size, number, secretory activity of thyroid cells.
* Activation of iodide pump
* ↑ Iodination of tyrosine & formation of thyroid hormones.

3. Feedback of thyroid hormones: ↑T3 &T4 →↓TSH by direct effect on hypothalamus →↓TRH

Question 19

17. Compare between mechanism of action of Parathormone & vitamin D3?

Answer 19

Mechanism of action of PTH: PTH binds to Gs→ activates adenyl cyclase →↑cAMP

Mechanism of action of 1,25(OH)2D3: binds cytoplasmic receptor → hormone-receptor complex → stimulates DNA transcription → mRNA →formation of Calbindin D ( Ca2+ transport)

Question 20

18.Give an account on the physiological actions of PTH?

Answer 20

1-On Bone:

A- Rapid phase: “osteolysis” Start in min, continues for hours
* ↑ permeability of osteolytic membrane to Ca2+ from bone fluid.
* ↑intracellular Ca2+are pumped into ECF by Calcium pump.

B- Slow phase: days or weeks to develop
* PTH stimulates osteoblasts production of IL-6 and RANKL →stimulates osteoclasts proliferation
* Osteoclasts resorb both organic & inorganic bone →releasing, Ca2+, PO4– into ECF

2- On Kidneys
* ↓ PO4—reabsorption in PCT
* ↑Ca2+ reabsorption in DCT
* ↑Mg2++ reabsorption, ↓H+ secretion

3- On the intestine: →↑Ca2+ , phosphate absorption

Question 21

19.Give an account on the physiological actions of calcitonin?

Answer 21

A- On bones:

• Stimulates osteoblasts
• ↓number & activity of osteoclasts→ ↓ bone resorption
• Inactivate Ca2+ pump of osteocyte

B- On kidneys: ↑ Ca2+ , PO4—excretion in urine

Question 22

20. Give an account on the physiological actions of 1,25 – DHCC?

Answer 22

A- On intestine.

*↑calbindin D in intestinal epithelium→↑ Ca transports from brush to basal border
*Amount of Ca2+ absorbed α amount of calbindin D.
*Stimulates Ca2+ ATPase in basal border & alkaline phosphatase

B- On bones: depend on Ca2+ & PO4– concentrations:

*High Ca2+ & PO4–→ stimulates osteoblastic activity.
* Low Ca2+ & PO4– and under the effect of 1,25DHCC,

C- On kidney: ↑calbindin D→↑ Ca2+ absorption by DCT , ↑phosphates reabsorption by PCT

Question 23

21. Factors regulating PTH

Answer 23

I- Regulation of PTH

1- Feedback of Plasma Ca2+: ↓plasma Ca2+ →↑ PTH secretion

2- ↑plasma PO4– →↓Ca2+ →↑PTH secretion
* PO4- also binds specific receptor in parathyroid gland →↑ PTH secretion.
* ↑PO4- →↑ (FGF23) →binds FGF-receptor in renal PCT →↓ PO4- reabsorption ‘

3- 1,25(OH)2D3→↓ PTH

4- ↑cAMP→↑PTH secretion.

Question 24

Factors regulating Vitamin D (1,25 DHCC)

Answer 24

II- Regulation of 1,25 DHCC

1- ↓ Plasma Ca2+ →↑ PTH → activate 1α hydroxylase→↑1, 25 DHCC

2- Feeds back of 1, 25 DHCC

• 1, 25 -DHCC has –ve feeds back on 1alpha hydroxylase→ ↓formation of 1,25-DHCC.
• 1, 25 -DHCC has +ve feeds back on convertase enzyme →↑24, 25 –DHCC (inactivation)

Question 25

Factors regulating of Calcitonin secretion

Answer 25

III- Regulation of Calcitonin Secretion: * ↑plasma Ca2+ →↓CT release * GIT hormones: gastrin, CCK →↑ calcitonin→ prevent post- prandial hyperecalcemia. * Beta adrenergic agonists, estrogen, prolactin, dopamine

Question 26

1. What is meant by Permissive Action of Glucocorticoids/ list some of these actions?

Answer 26

Presence of small amount of cortisol is required for 1- Catecholamines, Angiotensin II → VC 2- Catecholamines, Growth hormone → lipolysis 3- Glucagon → glycogenolysis