Endocrine Physiology

Principal endocrine gland:

1) Hypothalamus
2) Pituitary gland
3) Thyroid gland
4) Parathyroid gland
5) Pancreas
6) Adrenal glands
7) Testes and Ovaries (Gonads)
Organs with endocrine function:
Placenta (During pregnancy) Estrogen, progesterone, HCG
,HPL,HCS
Heart ANP,BNP,CNP
Stomach Gastrin(Antral G cell)
Small Intestine Secretin,Enterogastrone,CCK-PZ
Skin Vitamin-D
Pineal Gland Melatonin
Kidney Renin, Erythropoietin, Calcitriol,PG (Not calcitonin)
adipocytes Leptin

Organs with endocrine function:

Placenta (During pregnancy) Estrogen, progesterone, HCG
,HPL,HCS
Heart ANP,BNP,CNP
Stomach Gastrin(Antral G cell)
Small Intestine Secretin,Enterogastrone,CCK-PZ
Skin Vitamin-D
Pineal Gland Melatonin
Kidney Renin, Erythropoietin, Calcitriol,PG (Not calcitonin)
adipocytes Leptin
Hypothalamic (Releasing and inhibitory) hormones that control secretion on the anterior
pituitary gland:

releasing 1) Thyrotropin-releasing hormone (TSH)- Stimulates secretion of TSH

hormone
Corticotropin-releasing hormone (CRH Stimulates secretion of ACTH
Growth hormone-releasing hormone Stimulates secretion of
(GHRH)- growth hormone
Gonadotropin-releasing hormone (GnRH)- Stimulates secretion of FSH
and LH

inhibitory Prolactin or dopamine inhibitory hormone secretion of prolactin.

hormone Growth hormone-inhibitory hormone Inhibits secretion of GH
(somatostatin)-

Q. Integrating area related to following hormones are true.( Fcps part 1 surgery)
a. Anterior hypothalamus, response to heat
b. Posterior hypothalamus, response to thirst
c. Lateral superior hypothalamus is mainly for hunger
d.ventromedial hypothalamus is for cold
e.Lymbic is for fear and rage
Catecholamines Dorsal and posterior hypothalamus
Vasopressin Süpraoptic and paraventricular nuclei
Oxytocin Süpraoptic and paraventricular nuclei
Thyroid-stimulating hormone (thyrotropin, Para entricular nuclei and neighboring areas
TSH) via TRH Paraventricular nuclei

Adrenocortico tropic hormone (ACTH)* and

B-lipotropin (B-LPH Viä'CRH
: Follicle-stimulating hormone (FSH) and preoptic
luteinizing hormone (LH) via GnRH
Prolactin via PIH and PRH Arcuate nucleus; other areas (hypothalamus
inhibits secretion
Growth hormone via somatostatin and GRH Periventricular nucleus, arcuate nucleus
Thist V Lateral superior hypothalamus
Hunger Ventromedial, arcuate, and paraventricular
nuclei; lateral hypothalamus
Sexual behavior M Anterior ventral hypothalamus plus, in the
male, piriform cortex
Defensive reactions (fear, rage) Diffuse, in limbic systern and hypothalamus
Control of body rhythms Suprachiasmatic nudel
Classification of hormone:
a. on the basis of chemical nature:
1.Steroid: only 8 hormone: aldosterone, androgen, cortisol, estrogen, progesterone,
calcitriol( Active form of vit-D),Retinoic acid(metabolite of vit A) [ Tricks- sex hormone and
adrenal cortex hormone]- theses hormones also called sterol containing/cholesterol derivates.
2. amino acid tyrosine derivates: t3,t4, catecholamines( epinephrine and nor
epinephrine),dopamine or prolactin inhibitory hormone.
3. protein: Rest of all.

b.on the basis of location of receptor:

In the cell membrane Protein,cathecholamine
In the cytoplasm steroid
In the nucleus T3,t4
c. d. On the Basis of Mechanism:
Group 1- Hormone that bind to intracellular(cytoplasm and nucleus) receptors.
Group2- Hormones that bind to surface receptors and act by second messengers system.
Hormones those receptors present in nucleus and cytoplasm is act by gene activation(Gene
activation→DNA→Mrna(transcription)→Protein(Translation) and those receptors present in
cell membrane act by second messenger system.
Peptide : TRH, ADH, Oxytocin, Gnrh
Glycoprotein: FSH, LH, TSH, HCG (Tricks: to give a birth of brilliant baby)
Neuroendocrine hormone: ADH, Oxytocin- FCPS Surgery July -2023
Anabolic hormone: GH, Insulin,Thyroid, Steroid except cortisol( positive nitrogen balance/
protein synthesis)
Catabolic hormone: Cortisol, cathecholamines, Thyroxine , Glucagon.
Hormone causing lipolysis: Active hormone sensitive lipase
1. GH 2.Glucagon 3.Cortisol 4.Thyroid 5.Epinephrine ,sometimes (Tsh and acth)
Hormone causing lipogenesis: Active lipoprotein lipase
1.insulin 2. Thyroid.
Glands without pituitary gland:
Parathyroid, pineal, placenta, pancreas ( islets of Langerhans),kidney, adrenal medulla.–
Q. Protein hormones:
a. synthesized in rough ER
b. lipophilic
c. Having short duration of action
d. Act through second messenger system
e. Slow onset of action
ANSWER: T F T T F
Hormone acting through second messenger system:
PHATAL
Cyclic AMP(cAMP) P-Parathyroid hormone(PTH)
H-human chorionic gonadotrophin(HCG)
A- Adrenocorticotrophic hormone (ACTH)
T-Thyroid stimulating hormone(TSH)-Glycoprotein
A -Anti diuretic hormone(ADH)-V2 receptor-SBA
L- LH and FSH

Cyclic GMP ANP-Atrial natriuretic peptipe-Natriuresis

NO-Nitric oxide-vasodilator
Calcium-phospholipid system VC-GHOST
Phosphatidyl inositol system(ip3) V-Vasopressin
Phospholipase-c system C-Catecholamine
Diacyl glycerol(DAG) GH- Growth hormone and gonadotropins releasing
hormone
O-Oxytocin
S-Substance P
T-Thyrotropic releasing hormone (TRH)
 Pituitary hormone
All anterior pituitary hormones except prolactin are tropic hormones because they act on
other target endocrine gland to stimulate their hormone secretion. GH (somatotropic
hormone) is regarded as tropic hormone because it acts on liver to produce somatomedin that
cause growth.
Anterior pituitary hormone:
Cell types
Chromophilic (granular): a.Acidophilic (40%)
50%
Somatotropes Growth hormone
(Most abundant cell)
Mammotropes Prolactin
b.Basophilic (10%)
Thyrotropes Thyroid stimulating hormone
Gonadotropes Follicle-stimulating hormone
Luteinizing hormone
Chromopobes (agranular Corticotropes Adrenocorticotrophic hormone
cells): 50%
Q. Destruction of anterior pituitary causes:
a. amenorrhoea
b.diabetes insipidus
c.skin pallor
d.impaired ability to survive in severe stress
e. a fall in basal metabolic rate.
ANSWER: T F T T T
Functions of ACTH:
1. Growth of adrenal cortex.
2. Stimulation of glucocorticoid secretion.
3. Mild stimulation of adrenal androgen secretion.
4. 4.Stimulates melanocytes and causes skin pigmentation.
*ACTH has no effect on aldosterone secretion/- SBA
 Groth hormone: ↑ Glucose ↑ FFA ↓AA
Cortisol:↑ Glucose ↑ FFA ↓AA

Mode of action of gh:

Indirect action: Indirect action is its main action, acceleration of body growth by the formation
of somatomedians.
Direct action : Anti insulin effects- ↑ Glucose(pituitary diabetes)
↑ FFA( ketone body formation∕ketosis)
Functions of growth hormone:
General body growth: GH promotes growth of almost all tissue of body especially bone,
muscle, liver, kidne & alimentary tract by inereasing-
↑Size of the cell & Number of the cell.
Stimulates bone & cartilage growth: GH stimulates liver & other tissues to from some proteins
called somatomedins. Most important one is somatomedin C or Insulin-like growth factor- I
(IGF-1) which causes-
Chondrogenesis: linear length of cartilage.
Protein & Ca** deposition in chondrocyte & osteogenic cell. 1
Conversion of chondrocyte at epiphysial plate into osteogenic cell -> 1length
Osteoblast formation at periosteum -* fthickness of bone.
Of bone.
Thus, increased CHI secretion before fusion of epiphysis with diaphysis increases length &
thickness of bans and increased GH secretion after fusion of epiphysis with diaphysis increases
thickness of bone.
Function of growth hormone:
Metabolic function.
a.Increases protein deposition in tissues: By-
↑ Transport of amino acid into the cell.
↑ transcription of DNA to form -mRNA.
↑Translation of mRNA to cause protein synthesis.
↑ Breakdown of protein & amino acid.
b.lncreases fat utilization for energy: Under the influence of GH, fat is used for energy in pref
use of carbohydrates & proteins, GH causes-
↑ fatty acid mobilization from the adipose tissue.
↑conversion of fatty acids into acetyl Co-A which is used for energy production.
Ketogenic elector CHi. CH -/ Iplasma FFA-, Facetyl Co-A -* T'acetoacetic acid o
c.Increases plasma glucose level:
↓ glucose uptake in tissue
↑ glucose production by liver
insulin secretion, but also produce "insulin resistance" -› vinsulin's action.
Electrolyte metabolism:
↓ Na & K excretion through kidney.
↑ Ca & Mg absorption from GIT
↑ Plasma phosphorus
↓blood urea nitrogen

GH IGF 1
Sodium retention/ hypernatremia Insulin like activity
Decreased insulin sensitivity Antilipolytic activity
Lipolysis Protein synthesis
Protein synthesis Epiphysial growth
Epiphysial growth
Factors that stimulate or inhibit secretion of GH:
Stimuli that increase secretion Stimulai that decrease secretion
Hypoglycemia Increased blood glucose
Decreased blood FFA Increased blood FFA
Starvation or fasting, protein deficiency Aging
Trauma, stress, excitement Obesity
Testosterone REM sleep
Estrogen Cortisol
Exercise Glucose
Deep sleep (Stages II & IV) GHIH (Somatostatin)
GHRH GH (Exogenous)
2-Deoxyglucose Somatomedins (IGF-1)
Increase in circulating levels of certain amino acids Medroxyprogesterone
Protein meal
Infusion of arginine and some other amino acids
Glucagon
Pyrogen
Lysine vasopressin
Various psychologic stresses
L-Dopa and a-adrenergic agonists that penetrate the brain
Apomorphine and other dopamine receptor agonists

Traits Acromegaly Gigantism

Cause Hypersecretion of GH after Hypersecretion of GH before
fusion of epiphysis with fusion epiphysis with
diaphysis diaphysis( sba-july-2023)
Height Not increased Increased ( may be 7 - 8 feet)
Enlargement of hands and feet Occurs Does not occur
Protrusion of lower jaw Occurs occur
Kyphosis Develops Does not develop
Visceromegaly Enlargement of thyroid develop Enlargement of all
gland, heart & liver glands concerned with
metabolism
 Somatomedin
Somatomedins are polypeptide growth factors secreted by the liver & other tissues under the
influence of the growth hormone.
Types: 1. Insulin-like growth factor-1 (IGF-1) or somatomedin C or (mainly)
2. Insulin-like growth factor-II (IGF-Il)

Function: The effects of growth hormone on growth, cartilage, and protein metabolism
depend on an interaction between growth hormone and somatomedins.
Somatomedin Function
1.IGF-1 1. Skeletal and cartilage growth
2. Protein synthesis
3. Insulin like activity
2. IGF-II 1. Growth during fetal development.

Role of somatomedin on somatic growth: A current hypothesis suggests that growth hormone
and somatomedins can act both in cooperation and independently to stimulate pathways that
lead to growth.
Hormones of posterior pituitary:

hormone Synthesized by Chemical nature

Antidiuretic hormone or Supraoptic nuclei-5/6 Nonapeptide(9AA)
vasopressin Paraventricular nuclei-1/6
oxytocin Supraoptic nuclei-1/6 Nonapeptide(9AA)
Paraventricular nuclei-5/6

Hormones of thyroid gland:

Thyroxine
The hormones tri-iodothyronine (T3) and l-thyroxine (T4) are bound to thyroglobulin within
the colloid. Synthesis within the thyroglobulin complex is controlled by several enzymes,
in distinct steps:
● trapping of inorganic iodide from the blood;
● oxidation of iodide to iodine;
● binding of iodine with tyrosine to form iodotyrosine;
● coupling of monoiodotyrosines and di-iodotyrosines to form T3 and T4.

When hormones are required, the complex is resorbed into the cell and thyroglobulin is
broken down. T3 and T4 are liberated and enter the blood, where they are bound to serum
proteins: albumin, thyroxine-binding globulin (TBG) and
thyroxine-binding prealbumin (TBPA). The small amount of
hormone that remains free in the serum is biologically active.
The metabolic efects of the thyroid hormones are due
to unbound free T3 and T4 (0.3% and 0.03% of the total circulating hormones, respectively). T3
is the more important physiological hormone and is also produced in the periphery by
conversion from T4. T3 is quick acting (within a few hours), whereas T4 acts more slowly (4–14
days
Target tissue Effects Mechanism
Heart Chronotropic Increased number adrenergic receptors
And Enhanced responses to circulating catecholamines
Inotropic Increased proportion of a-myosin heavy chain (with
higher ATPase activity)
Adipose tissue catabolic Stimulated lipolysis
Muscle catabolic Increased protein breakdown
bone development Promote normal growth and skeletal development
Nervous system development Promote normal brain development
Gut metabolic ↑ rate of carbohydrate absorption intestine.
Lipoprotein metabolic Formation of LDL receptors(↓Cholesterol)
Other Calorigenic Stimulated oxygen consumption by metabolically active
tissues (exceptions: testes, uterus, lymph nodes, spleen,
anterior pituitary) Increased metabolic rate.(LUSTAB)
Physiological actions of t3 and t4:
Metabolic function:
On CHO metabolism ↑Uptake of glucose by cell.
↑Glycolysis
↑Gluconeogenesis
↑Glucose absorption from GIT
↑Insulin secretion
On fat metabolism Fatty acid mobilization from the adipose tissue •
Plasma FFA
Plasma cholesterol, triglyceride, phospholipid levels
On protein Synthesis of large number of protein enzymes, structural proteins,
metabolism and transport proteins
Basal metabolic rate Because thyroid hormones increase metabolism in almost all cells of
(BMR) the body, BMR is increased.
Body weight Increased thyroid hormones decreases body weight & vice versa.
Vitamin As thyroid hormones increase the metabolism, vitamin requirement i
requirement also increased.
Calorigenic actio , consumption by metabolically active tissues (except adult brain,
testis, uterus, lymph nodes, spleen, and anterior pituitary
Effects on CVS THeart rate
Force of contraction of the heart
Cardiac output
Blood flow to most tissue to supply more O, for increased metabolism
Mean pressure normal
Effects on CNS Promotes normal brain development
Effects on Rate & depth of respiration
respiration
Effects on git 1 - w1 Appetite and food intake v1 Motility of the GIT ets on GIT v1
Secretion of digestive juices v4 Rate of carbohydrate absorption
Effects on Promote protein breakdown
Effects on Promote normal growth and skeletal development
Effects on Hyperthyroidism->y Sleep ets on sleep ~ Hypothyroidism -> 1 Sleep
Effects on
Effects on Secretion of most other endocrine glands
Endocrine gland
Effects on For normal sexual function, thyroid secretion needs to be
approximately normal. ets on sexual function * In man, lack of thyroid
hormones causes loss of libido and great excess of hormone causes
impotence. * In woman, lack of thyroid hormones cause loss of libido,
menorrhagia, polymenorrhea, even
-
Primary hyperthyroidism ↑T3 ↑T4 TSH
Secondary hyperthyroidism ↑T3 ↑T4 ↑TSH
Sub-clinical hyperthyroidism N-T3 N-T4 TSH

Difference between T4 and T3 :

T4 T3
Synonym Thyroxin Less Triiodothyronine
No. of iodine 4(four). 4(four)
Found in Circulation intracellularly
Potency Less potent 3-5 times more potent
Affinity to receptor Less More (10 times)
Onset of action Slow Rapid
Duration of action Prolong Short
Plasma half-life 6.5 days 1.5 day

Causes of Hypothyroidism:
Autoimmune Hashimoto's thyroiditis - Most common
Spontaneous atrophic hypothyroidism
'Graves' disease with TSH receptor-blocking + antibodies

latrogenic. Radioactive iodine ablation

Thyroidectomy
Drugs:Carbimazole, methimazole, propylthiouracit,Amiodarone,
Lithium
+ Transient Subacute (de Quervain's) thyroiditis
thyroiditis Post-partum thyroiditis
Iodine deficiency in mountainous regions
Congenital Dyshormonogenesis ,Thyroid aplasia
Thfiltrative Amyloidosis, Riedel's thyroiditis, sarcoidosis etc.
Secondary TSH deficiency
hypothyroidism
Features:
1. Decreased BMR and cold intolerance.
2. Weight gain despite relative lack of appetite.
3. Puffy face with bagginess under eyes, Slow and husky voice. sub clinical Hyper - TSH.
4. Accumulation of mucopoly saccharide (MPS) that promotes water retention in ground
substance of skin leading to thickening & puffiness of skin.
5. Poor memory and slow mentation in thought, speech, action. A Menstrual blood
6. Free water retention leading to swelling of body.
7. Menstrual irregularities, loss of libido, impotency, infertility. 1 Chobsterol
8. Muscle weakness, cramps & stiffness

Frequency
Graves' disease
Multinodular goitre
Solitary thyroid adenoma
Thyroiditis
Subacute (de Quervain's)?
Post-partum
Jodide-induced
Drugs (e.g. amiodarone)? Radiographic
contrast media? - Iodine prophylaxis
programme?

Extrathyroidal source of thyroid hormone

Factitious thyrotoxicosis
Struma ovarii

TSH induce
-secreting pituitary adenoma
Choriocarcinoma'and hydatidiform mole

Follicular carcinoma + metastases V

Clinical features: 1. Goiter 2. Gastrointestinal: a. Weight loss b. Anorexia 3. Cardiorespiratory:
a. Plapitations b. Atrial fibrillation c. Cardiac failure. d. Dyspnea on Exertion 4. Neuromuscular:
a. Nervousness b. Irritability c. Emotional liability d. Muscle weakness
5. Dermatological: a. Increased sweating b. Pigmentation c. Pretibial myxedema 6. Ocular: a.
Exophthalmos b. Lid retraction, lid lag c. Loss of visual acuity 7. Others: a. Heat intolerance b.
Fatigue c. Osteoporosis d. Thirst
-
Adrenal cortex hormone: all are steroid hormones.

Zona Minerocorticoids-Aldosterone (very potent, aetivity) accounts for about of

glomerulosa all mineralocortic Deoxycorticosterone
Corticosterone
Cortisol

Zona Cincocorticorda Cortisol (very potent, accounts for about.559) Y of all

fasciculata glueesorticeid activi Corticosterone (provide 4% of all glucocorticoid activity)
Zona SeX hormones:
raticularis Adrenal androgens: Dehydroepiandrosterone, androstenedione
Estrogens

Adrenal medulla: Catecholamine (Epinephrine, Norepinephrine, Dopamine)

Adrenocortical dysfunctions
Cushing's syndrome
Addison's disease
Adrenal hyperplasia
Adrenal crisis
Primary aldosteronism or Conn's syndrome Adrenogenital syndrome.
 CUSHIN’G SYNDROME

Classification of Endogenous Cushing's Syndrome:

ACTH-dependent - 80%
• Pituitary adenoma secreting ACTH (Cushing's disease) - 70%_
• Ectopic ACTH syndrome (bronchial carcinoid, small-cell lung carcinoma, other neuro-
endocrine tumour) - 10%
Non-ACTH-dependent - 20% • Adrenal adenoma - 15% • Adrenal carcinoma - 5% •ACTH-
independent macronodular hyperplasia; primary pigmented nodular adrenal disease;
McCune-Albright fyndrome (together €1%)
Hypercortisolism due to other causes (also referred to as pseudo-Cushing's syndrome)
• Alcohol excess (biochemical and clinical features
• Maior depressive illness (biochemical features only, some clinical overlap) • Primary
obesity (mild biochemical features, some clinical overlap) ÀCTH = adrenocorticotrophic
hormone)

Clinical features:
1.Central far depositon
Moon face (due to deposition of fat on face)
Buffalo hump (due to deposition in trunk)
Pendulous abdomen (due to deposition of fat in the abdomen)
2.Reddish purple abdominal striae( transverse)
3.Wasting and weakness of proximal muscle wasting( negative nitrogen balance)
4.Osteoporosis
5.Poor wound healing
6.Hypertension and hypervolemia(salt and water retension due to aldosterone like activity)
7.urinary potassium loss, hypokalaemia and metabolic alkalosis
8. Hyperglycemia
Cushing's disease: When Cushing's syndrome occurs due ton ACTH secreting ant. Tumour then
it is called cushing’s disease.
hypoadrenalism
Primary hypoadrenalism/ Addison's disease:The clinical condition characterized by
hyposecretion of adrenal cortex.
Metabolic features: J.
1.Features of cortisol deficiency"
Increased insulin sensitivity & hypoglycemia.
Anorexia, vomiting, malaise, weakness & weight loss.
2. Features of aldosterone deficiency.
Renal salt and water loss.
Weight loss, hypotension, shock.
Hyponatremia, hyperkalemia, metabolic acidosis.
3. Features of ACTH excess. *
Hyperpigmentation of skin./ Nelson syndnome. [
Hyperpigmentation of buccal mucosal.
4.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.

Q.Features of acute adrenal crisis:

a. circulatory shock
b.hypernatremia
c.hyperkalaemia
d.hypoglycaemia
e.hypocalcaemia
ANSWER:T F T T F

hyperadrenalism
HYPERALDOSTERONISM DOG, rOWNS SYNDROME (PRIMARY HYPERALDOSTERONISMO* 'cially
serfinition: It is the primary hyperaldosteronism characterized by increased aldosterone
secretion due to adrenal rauses. Causes: Y. Aldosterone producing adenoma (APA) of adrenal
cortex. 2. Bilateral idiopathic adrenal hyperplasia (IAH). -18.42) Metabolic features: J. Salt and
water retention leading to hypervolemia, edema and hypertension. 2. Increased total sodium
content of body & hypernatremia 3. Kaliuresis leading to hypokalemia and decreased total K*
content of body. # Metabolic alkalosis & tetany: 3. Decreased plasma renin concentration due
to suppression of renin angiotensin aldosterone system * (RAAS). Laboratory findings in conn's
syndrome: J: Increased urinary potassium excretion & hypokalemia 1. Increased plasma
aldosterone 3. Increased urinary aldosterone excretion ichsel «. Decreased plasma renin
concentration - SBA B. SECONDARY HYPERALDOSTERONISM • It happens due to the
stimulation of RAAS by extrarenal causes. • Important causes are
Renal hypoperfusion, e.g. hypovolemia, nephrosis, cirrhosis liver, CCF etc. Renin secreting
tumor.
• Frequently present with hypovolemia & hyponatremia. • Here increased plasma renin
concentration found. (Ref: ABC Biochemistry/S" /p

Cholecalciferol {Vitamin D3}

Liver

inhibition
25- Hydroxycho1ecalciferol
Kidney

Activation
Parathyroid

hormone
RU-06Ju) nathesis of medullary hormones / catecholamines: The principal catecholamines are
formed by athesis of medullary hormones / contecholamine, The principal of tit tyrosine is
forensons and enylalanine, but most is of dietary origin. Tyrosine is transported into
Catecholamine-secreting neurons and renal medullary cells by a concentrating mechanism. |
TIO Tyrosine hydroxylase 1. Tyrosine
Dopa (rate-limiting step)
Dopa decarboxylase 2. Dopa :
Dopamine
Transport of dopamine from the cytoplasm into the chromaffin vesicles. b is robbeld that
verbin Dopamine ß - hydroxylase 4. Dopamine -> Norepinephrine robbeld visaiti N-methyl
transferase 5. Norepinephrine -> Epinephrine. Oh (Ref: Ganong's-24" /145-146;
Guyton-12th/732) / to know radation of catecholamines: The catecholamines are inactivated
by oxidative deamination, catalyzed
Endocrinology Circulatory Changes Caused by Epinephrine and Norepinephrine

Norepinephrine Epinephrine(heart)
Predominant adrenergic action (a>B) Predominatley activates B-adrenergic System
(B> g)
Potent vasoconstriction Weak vasoconstriction
Increase heart rate Increase heart rate
Increase force of contraction Increase force of contraction Vasodilatation
Vasoconstriction (increase TPR) (decrease TPR)
Increase blood pressure (both systolic and Increase systolic pressure Decrease diastolic
diastolic) pressure
Widening of the pulse pressure
V Baroreceptors stimulation causes reflex Baroreceptors stimulation is insufficient to
bradycardia that overrides the toral obscure the direct effects of epinephrine on
cardioaccelatory effects the heart rate and cardiac output V
So, effects of norepinephrine on the So, effects of epinephrine on the circulatory
Circulatory system are: system are:
Decrease heart rate Increase heart rate.
Decrease cardiac output Increase cardiac output
Increase TPR Decrease TPR
Increase blood pressure Widening of pulse pressure
 ENDOCRINE PANCREASE
Four types of cells present in endocrine portion of pancreas.

Insulin
INSULIN Ysflacture, synthesis, secretion & fate of insulin 4 DIS ADIR «insulin is a poly peptide
composed or 51 amino acids arranged in two polypeptide chains (A & B) connected by two
disulfide bonds. Chain À, contam 21 Tamino acids & chain B, contain 30 amino acids. «nsulin is
synthesized in rough endoplasmic reticulum of pancreatic B-cells as preproinsulin, a single
chain polypeptide consisting of 106 amino acids! mmediately after synthesis microsomal
enzyme cleaves preproinsulin to proinsulin which is a single chain-A and which is á single chain
polypeptide of 82 amino acids, but folded as chain-A and chain-B connected by à connecting
segment called connecting peptidd §(C-peptide) Chain-A and chain-B are also cross connected
by disulfide bonds Proinsulin is transported to Golgi apparatus for packaging and storage. Now
by the process of proteolysis, C-peptide (31 amino acids, MW 3000) is a splitted off and insulin
is produced, which is composed of chain-A (21 amino acids) and chain-B (30 amino acids^
connected by disulfide bonds. Insulin is stored in the cytosol in granules & released to blood by
exocytosis if proper stimulus is given wC-peptide and native insulin are secreted in blood in
equimolar proportion. C-peptide has no biological activity of insulin but it is a good indicator of
insulin production & secretion. Normal fasting concentration of C-peptide is 1-2 ng/ml with
half life longer than insulin. Normal fasting concentration of insulin is 0.2-0.8 ng/mI with half
life about 06 in Insulin is degraded by proteases present in liver & kidney, GENESIS
Figure: Mechanism of insulin action (Ref: Guyton-12/941) C peptide • Proinsulin is transported
from RER to the Golgi apparatus, where it is cleaved to form insulin & connecting peptide (C
peptide). Normally, 90-97% of the product released by the B cells is insulin along with
equimolar amounts of C peptide. C peptide has no biological activity. It enters the circulation
through the portal system. Its half life is longer than insulin and is about 35 minutes. During
fasting condition, C peptide level is higher than insulin. It is not metabolized by the liver. It is
removed from circulation by the kidney and degraded with a fraction excreted unchanged in
urine. (Ref:
Principal action of insulin:
Rapid action ( within Increased transport of glucose, amino acid and K* into
seconds) insulin- sensitive cells.
• Stimulates protein synthesis • Inhibition of protein
degradation " Activation of glycolytic enzymes and glycogen
synthase. " Inhibition of phosphorylase and gluconeogenic
enzymes. -
Delayed action Increase in mRNA for lipogenic and other enzymes

Actions os insulin:
type liver Skeletal muscle Adipose tissue
Carbohydrate Glycogenesis Glycolysis Glucose uptake
metabolism Glycolysis Glycogenesis Lipo genesis from
Glycogenolysis Glycogenolysis glucose
Gluconeogenesis

Protein metabolism Protein synthesis Amino acid uptake

Amino acid uptake Protein synthesis
Protein catabolism
Release of glucogenic
amino acis

Fat metabolism ↑Lipogenesis ↑Ketone uptake Fatty acid synthesis

ketogenesis Glycerol phosphate
synthesis
Tg deposition
Lipoprotein lipase
Hormone sensitive
lipase
K uptake ↑ ↑
General
Factors affecting insulin secretion:
Inhibitors
1. Glucose 1. Somatostatin
2. Mannose 2. 2-Deoxyglucose
3. Amino acids (leucine, arginine, others) 3. Mannoheptulose
4. Intestinal hormones (GIP, GLP-1, gastrin, 4. a-Adrenergic stimulators (norepinephrine,
secretin, CCK; others) epinephrine)
5. B-Keto acids x5. B-Adrenergic blockers (propranolol) 6.
6. Acetylcholine Galanin 7. Diazoxide 8. Thiazide diuretics 9.
7. Glucagon K* depletion 10. Phenytoin 11. Alloxan 12.
8. Cyclic AMP and various cAMP-generating Microtubule inhibitors 13. Insulin
substances
9. B-Adrenergic stimulators
10. Theophylline
11. Sulfonylureas
Effects of insulin on various tissues:

Adipose tissue Increased glucose entry

Increased fatty acid synthesis
Increased glycerol phosphate synthesis
Increased triglyceride deposition
Activation of lipoprotein lipase
Inhibition of hormone-sensitive lipase
Increased K* uptake
Muscle Muscle Increased glucose entry Increased glycogen synthesis Increased
amino acid uptake Increased protein synthesis in ribosomes Decreased
protein catabolism Decreased release of gluconeogenic amino acids
Increased ketone uptake Increased K* uptake
Liver Decreased ketogenesis Increased protein synthesis Increased lipid
synthesis Decreased glucose output due to decreased gluconeogenesis,
increased glycogen synthesis, and increased glycolysis General
Factors affecting glucagon secretion:
Stimulators Inhibitors
Amino acids (particularly the glucogenic amino acids: Glucose
alanine, serine, glycine, cysteine, and threonine) Somatostatin
CCK, gastrin Secretin
Cortisol FFA
Exercise Ketones
Infections Insulin
Other stresses Phenytoin a-Adrenergic
B-Adrenergic stimulators stimulators
Theophylline GABA
Acetylcholine
Differential features of honc and dka:

parameter Honc- Type 2 Dka- type 1

pathophysiology Hyperglycaemia(SBA)→glycosuria Insulin lack→ DM →lipolysis→
→osmotic diuresis→ salt and water ffa in plasma→ Acetyl CoA
depletion→ severe dehydration→ →Ketoacids→ Diabetic
hypotension →coma( hyper ketoacidosis
osmolar coma) →death
Plasma glucose 800-1400 mg/dl 300-800 mg/dl
Osmolality 330-350 <330
ph normal <7.2
Serum sodium elevated Low
Serum potassium elevated
Serum bicarbonate ++ +
Haematocrit +++ ++
 Endocrine
Semen:It is the fluid that is ejaculated at the time of orgasm, and contains sperms and the
secretions of the sentinal vesicles, prostate, Cowper's glands, and probably the urethral
glands.
Average volume: 2.S - 3.5 mL / ejaculation. The volume of the semen and the sperm count
decreases rapidly with repeated ejaculation.
composition of human semen: 1. Color: White, opalescent 2. Specific gravity: 1.028 3. рН: 7.35
- 7.50 amonn POI 4. Sperm count: Average about 100 million/mL, with fewer than 20 %
abnormal forms.
Other components:

1.Fructose (1.5 - 6.5 mg/mL) From seminal vesicles (contributes 60 % of

2. Phosphorylcholine total volume)
3. Ergothioneine
4. Ascorbic acid
Flavins
Prostaglandins

Spermine ,Citric acid From prostate (contributes 20 % of total

Cholesterol,Phospholipids volume)
Fibrinolysin, Fibrinogenase,Zinc
Acid phosphatase

Hyaluronidase Buffers
Hosphate
bicarbonate

Exocrine function: Production of sperm. 2. Endocrine function: Cells Leydig cells Sertoly cells
Inhibin Testostefone Dihydrotestosterone Hormones и Testosterone" K_Inhibin. 2. Androgen-
binding protein (ABP) •Mullerian inhibiting substance (MIS) S. Estrogen 'unctions of
Testosterone:
hormonal regulation of spermatogenesis:
1.From puberty, hypothalamus begins to release GnRH which stimulates ant. pituitary to
secrete FSH & LH
2. LH stimulates the Leydig cells of testis to secrete testosterone.
3. Testosterone causes the growth & divisions of the testicular germinal cells which is the first
step in forming the sperms. VTIE
4. Stages from the spermatogonia to the spermatids appear to be independent of androgens.
S. FSH & testosterone stimulates the Sertoli cells & without this stimulation, the conversion of
spermatid to sperm (the process of spermiogenesis) will not occur. Thus, to initiate
spermatogenesis, both FSH and testosterone are necessary.
6. When the seminiferous tubules fail to produce sperm, secretion of FSH increases markedly.
Conversely, when spermatogenesis proceeds too rapidly, pituitary secretion of FSH diminishes.
Inhibin acts directly on the anterior pituitary to inhibit FSH secretion.
7. Estrogen is probably essential for spermiogenesis.
8. GH promotes early division of spermatogonia.
 Male sex hormone Hormones sex hormone Hormones
1. Testosterone (mainly) Testis Estrogen Ovary, adrenal cortex &
2. Dihydrotestosterone placenta
3.Androstenedione Progesterone Ovary, adrenal cortex &
4. Inhibin placenta
Relaxin Ovary
Inhibin Ovary
Adrenal androgens- adrenal cortex
Dehydroepiandrosterone

Functions of Testosterone:

In male fetus: Causes masculinizing effects-

1. It is responsible for the sex differentiation. Increase in libido.
2. Causes the development of external & internal genitalia. Enlargement of clitoris
3. Causes the descent of the testes. Growth of hair on the face.
In adult male:
1. Causes enlargement of penis, scrotum & testes after L. Inhibits LH) secretion from
puberty. the anterior pituitar
2. Develops & maintains secondary sexual characteristics.
3. It is essential for the initiation and maintenance of
spermatogenesis.
4. 1 Musculature by increasing protein synthesis.
5. 1 Size and strength of bones.
6. 1 Basal metabolic rate (BMR) 7. 1 RBC count.
8. 1 Size of the kidney.
9. Increases the retention of Na?+ , SO42-, PO4, and H2O.
10. Inhibits LH secretion from the ant. pituitary.
Hormones acting on female breast:
Hormones Action on beast
Estrogens • Cause the ductal system of the breasts to grow & branch. • Increases
the stroma of the breast in quantity. • Deposition of large quantities of
fat in the breast. • Enlargement of breast
•Stimulates the growth of lobules and alveoli • Stimulates the
development of secretory characteristics in the cells of the alveoli
• Stimulates milk secretion into the alveoli
SStimulates milk ejection from alveoli into ducts Causes the contraction
of myo-epithelial cells lining the duct walls, with consequent ejection of
milk through the nipple
It is lactogenic
These hormones are important in growth of the ductal system.
stimuli that cause oxytocin release: in Primary stimuli > Stimulation of nipple e) secondary
stimuli = Uterine & vaginal distension Os stressful stimuli Functions: Inc No metabolic &
electrolyte function J. General function: On pregnant uterus & On breast -help in praturation &
help in milk ejection 3 Specal function: On com pregnant Iterus- Receptive contraction a
rachinese spent ejection. On corpus luteum: Luteolysis -regression of corpus Tuteum.
Therapetic oxytocin: Used to induce labor YActions ofOxytocin" FePs actin Milk ejection:
Oxytocin causes contraction of myoepithelial cells that surround the mammary alveoli. Thus,
ejects milk from the alveoli into the duct & thence out of the nipple (milk ejection) & thus,
helps in breast-feeding. 2. Effect on pregnant/ gravid uterus: At the time of delivery, oxytocin
secretion is increased and it causes contraction of the uterus. Thus it helps in birth of thebaby.
3 Effect on non-pregnant uterus: During sexual intercourse, oxytocin is released, causes
contraction of uterus and thus helps transport of the sperm through female genital tract to the
uterine tube. se in male: In male, oxytocin secretion is increased during ejaculation and it is
possible that this increase causes increased contraction of the smooth muscle of the vas
deferens, propelling sperm toward the urethra. 20 Control of Oxytocin Secretion Oxytocin
secretion is controlled by neuroendocrine reflex, having- ". A fferent impulse ->neural 2.
Efferent impulse ?hormonal (oxytocin) Two major stimuli stimulate thereflex to cause release
of oxytocin- - Sucking the nipple • Distension of the cervix & vagina. J. Milk ejection reflex (let
down reflex): Milk is secreted continuously into the alveoli of the breasts, but it docs not flow
easily from the alveoli into the ductal system and, therefore, does not continually leak from
the breast nipples. Instead, the milk must be ejected from the alveoli into the ducts before the
baby can obtain it. This is caused by a combined neurogenic and hormonal reflex that involves
the oxytocin, as follows. Sucking the nipple of the breast of the lactating mothe V Via somatic
nerve Sensory impulse goes to the mother's spinal cord Impulse then goes to the supraoptic &
paraventricular nuclei of the hypothalamus Discharge of oxytocin containing neurons "Causes
secretion of oxytocin from the post pituitary Y . Oxytocin is carried by blood to the breasts
Causes contraction of the myoepithelial cells that surround the mammary alveoli - . F V - This
contraction ejects milk from the alveoli into the duct & thence out of the nipple vr - Milk
ejection