ENDOCRINOLOGY

PHYSIOLOGY

Hormones
Hormones are chemical messengers produced and secreted by endocrine
glands directly into the bloodstream, where they travel to target organs or tissues
to regulate various physiological processes. Hormones play a key role in growth,
metabolism, reproduction, stress response, and homeostasis.

Diff between endo and exocrine glands

Endocrine glands are specialized glands that release hormones directly into the
bloodstream. These hormones travel through the blood to target distant organs or
tissues, where they regulate various physiological processes such as growth,
metabolism, and reproduction. Endocrine glands are ductless, meaning their secretions
are not carried by ducts. Examples include the pituitary gland, thyroid gland, adrenal
glands, and the endocrine portion of the pancreas.

In contrast, exocrine glands secrete their products through ducts to specific locations,
either onto body surfaces (such as the skin) or into body cavities (such as the digestive
tract). These secretions are not hormones but substances like enzymes, mucus, sweat,
or saliva, which serve localized functions like digestion, lubrication, or temperature
regulation. Examples of exocrine glands include salivary glands, sweat glands, and the
exocrine part of the pancreas.

The key distinction lies in the mode of secretion: endocrine glands use the bloodstream
for their secretions, while exocrine glands utilize ducts to deliver their products to
specific sites.

CONTROL OF PITUITARY SECRETIONS

Control of Anterior Pituitary
•It has no neural connection with the hypothalamus
•There is a capillary plexus in the hypothalamus
•It gives rise to the Hypothalamic-hypophyseal portal system
•Neurohormones from hypothalamus pass through this portal system to stimulate or
inhibit the anterior pituitary

Hypothalamic Control of Pituitary Secretions with Reference to the

Hypothalamo-Hypophyseal Portal System

The hypothalamus controls the pituitary gland through a combination of hormonal and
neural mechanisms:

1.​ Anterior Pituitary Control via the Hypothalamo-Hypophyseal Portal System:​

 ○​ The hypothalamus produces releasing and inhibitory hormones, which are
secreted into the primary capillary plexus located in the hypothalamus.
○​ These hormones travel through the portal veins to the secondary
capillary plexus in the anterior pituitary.
○​ Upon reaching the anterior pituitary, these hormones regulate the
secretion of specific pituitary hormones into the systemic circulation to act
on their target tissues.
2.​ Posterior Pituitary Control via Neural Connections:​

○​ The hypothalamus synthesizes oxytocin and antidiuretic hormone

(ADH), which are transported via axons in the
hypothalamo-hypophyseal tract to the posterior pituitary.
○​ These hormones are stored in the posterior pituitary and released directly
into the bloodstream in response to neural signals.

Hormones Secreted by the Anterior Pituitary

The anterior pituitary produces and releases the following hormones:

1.​ Growth Hormone (GH): Promotes growth and regulates metabolism.

2.​ Prolactin (PRL): Stimulates milk production in the mammary glands.
3.​ Thyroid-Stimulating Hormone (TSH): Stimulates the thyroid gland to produce
thyroid hormones (T3 and T4).
4.​ Adrenocorticotropic Hormone (ACTH): Stimulates the adrenal cortex to
release cortisol.
5.​ Follicle-Stimulating Hormone (FSH): Supports ovarian follicle development and
spermatogenesis.
6.​ Luteinizing Hormone (LH): Triggers ovulation and stimulates the production of
sex hormones (estrogen, progesterone, and testosterone).

Hypothalamic Releasing and Inhibitory Hormones

1.​ Releasing Hormones:​

○​ Thyrotropin-Releasing Hormone (TRH): Stimulates the release of TSH

and prolactin.
○​ Corticotropin-Releasing Hormone (CRH): Stimulates the release of
ACTH.
 ○​ Gonadotropin-Releasing Hormone (GnRH): Stimulates the release of
FSH and LH.
○​ Growth Hormone-Releasing Hormone (GHRH): Stimulates the release
of GH.
2.​ Inhibitory Hormones:​

○​ Somatostatin (Growth Hormone-Inhibiting Hormone, GHIH): Inhibits

the release of GH and TSH.
○​ Dopamine (Prolactin-Inhibiting Hormone, PIH): Inhibits the release of
prolactin.

Hormones Secreted by the Posterior Pituitary

The posterior pituitary releases two hormones, synthesized in the hypothalamus:

1.​ Oxytocin: Stimulates uterine contractions during childbirth and milk ejection
during breastfeeding.
2.​ Antidiuretic Hormone (ADH or Vasopressin): Regulates water balance in the
body by increasing water reabsorption in the kidneys and constricting blood
vessels.

Secretion, Transport, and Clearance of Hormones

1. Secretion of Hormones

Hormones are secreted by endocrine glands in response to specific stimuli such as

neural signals, chemical changes in the blood, or regulatory feedback loops. The
secretion mechanisms vary based on the hormone type:

●​ Peptide and Protein Hormones: Synthesized as precursors, stored in secretory

vesicles, and released via exocytosis (e.g., insulin, GH).
●​ Steroid Hormones: Synthesized from cholesterol in response to demand and
released directly into the bloodstream (e.g., cortisol, estrogen).
●​ Amine Hormones: Derived from amino acids (e.g., thyroid hormones from
tyrosine) and secreted either directly or stored until release is triggered.

2. Transport of Hormones

●​ Water-Soluble Hormones:
 ○​ Peptide and protein hormones dissolve in plasma and circulate freely.
○​ Example: Insulin.
●​ Lipid-Soluble Hormones:
○​ Steroid and thyroid hormones bind to carrier proteins (e.g., albumin,
globulins) for transport in the bloodstream.
○​ Example: Thyroxine (T4) binds to thyroxine-binding globulin (TBG).

Binding to carrier proteins extends the half-life of hormones and regulates their
availability to target tissues.

3. Clearance of Hormones

Hormones are removed from the bloodstream through:

●​ Metabolic Degradation: Hormones are broken down in the liver or kidneys.

●​ Excretion: Metabolites are excreted via urine or bile.
●​ Receptor-Mediated Endocytosis: Hormone-receptor complexes are
internalized and degraded.

The half-life of hormones varies; for example, peptide hormones have shorter
half-lives, while protein-bound hormones like thyroid hormones have longer half-lives.

PINEAL GLAND : functions

Pineal Gland Overview

Anatomy and Structure

●​ Location:
Arises from the roof of the third ventricle in the diencephalon.
●​ Encapsulation: Surrounded by meninges.
●​ Cellular Composition: Contains glial cells and pinealocytes, indicative of its
secretory function.
●​ Blood Supply: Highly vascularized with permeable, fenestrated capillaries; its
blood supply is second only to the kidneys.

Functions of the Pineal Gland

1.​ Regulation of the Sleep-Wake Cycle:​

 ○​ Synthesizes and secretes melatonin, which is crucial for maintaining
circadian rhythms.
2.​ Reproduction and Sexual Function:​

○​ Influences the hypothalamic-pituitary-gonadal axis, affecting reproductive

hormones and sexual maturation.
3.​ Self-Repair and Immunity:​

○​ Melatonin enhances immune function and has antioxidant properties for

cellular repair.
4.​ Spiritual and Psychological Aspects:​

○​ Sometimes referred to as the "seat of the soul" in spiritual traditions,

associated with intuition, meditation, and mood enhancement.
5.​ Longevity and Anti-Aging:​

○​ Melatonin's antioxidant properties contribute to reducing oxidative stress,

slowing aging, and preventing age-related diseases.

Melatonin: Synthesis, Secretion, and Function

Melatonin Synthesis

●​ Mechanism:
○​ N-acetylation and O-methylation of serotonin occur in pinealocytes.
○​ The process is light-sensitive: synthesis increases in darkness and
decreases with light exposure.

Melatonin Secretion

●​ Day-Night Variation:
○​ Day: Melatonin levels are low.
○​ Night: Levels peak, with maximum secretion during deep sleep (around 1
AM).
●​ Regulation:
○​ Norepinephrine, released by postganglionic sympathetic nerves,
stimulates melatonin production via beta-adrenergic receptors.
○​ Increased cAMP activity enhances N-acetyltransferase, which catalyzes
melatonin synthesis.

Metabolism of Melatonin
 ●​ Rapidly metabolized in the liver through 6-hydroxylation, followed by
conjugation.
●​ Over 90% of melatonin metabolites are excreted in urine as 6-hydroxy
conjugates or 6-sulfatoxymelatonin.

Day vs. Night Melatonin

Daytime Melatonin (90%)

●​ Source:
Subcellular melatonin, primarily from mitochondria.
●​ Production: Stimulated by near-infrared rays (e.g., sunlight exposure).
●​ Functions:
○​ Acts as a powerful antioxidant, killing cancer cells and preventing aging.
○​ Enhances mitochondrial function, producing energy (ATP) for metabolic
activities.

Nighttime Melatonin (10%)

●​ Source:
Secreted by the pineal gland into the bloodstream.
●​ Production: Peaks in darkness and deep sleep.
●​ Functions:
○​ Maintains circadian rhythms, connecting the body to nature’s cycles.
○​ Prevents cancer, aging, osteoporosis, and menstrual irregularities.

Factors Affecting Melatonin Levels

1.​ Reduced Melatonin at Night:​

○​ Caused by jet lag, night shifts, poor vision, or insomnia.

2.​ Circadian Rhythm Disturbance in Insomnia:​

○​ Difficulty falling asleep at night and waking up in the morning due to

disrupted melatonin cycles.

Functions of Melatonin
 1.​ Regulates Circadian Rhythms:​

○​ Synchronizes physiological processes with light-dark cycles via the

suprachiasmatic nucleus (SCN).
2.​ Antioxidant Effects:​

○​ Neutralizes free radicals, protecting against cellular damage and aging.

3.​ Immune System Strengthening:​

○​ Enhances the body's defense mechanisms against diseases.

4.​ Role in Neurological Disorders:​

○​ Altered melatonin levels are linked to conditions like autism and

Parkinson’s disease.

GROWTH HORMONE
Growth Hormone is a peptide hormone produced from Pituitary under the influence of GHRH
Regulation of Growth Hormone Secretion

Stimulatory Factors

●​ Starvation/Fasting
●​ Increased amino acids in blood
●​ Hypoglycemia/low fatty acids
●​ Exercise
●​ Excitement, trauma, stress
●​ Deep Sleep (Stages II and IV)
●​ Ghrelin, testosterone, estrogen

Inhibitory Factors

●​ Increased blood glucose

●​ Increased blood free fatty acids
●​ REM sleep
●​ Aging
●​ Obesity
●​ Somatostatin (GHIH)
●​ Exogenous growth hormone
●​ Somatomedins (IGF-1)
Growth Hormone (GH) exerts many of its effects through intermediate substances
called somatomedins, also known as Insulin-like Growth Factors (IGFs), primarily
IGF-I.

Short Duration of Action of Growth Hormone

●​ GH itself has a relatively short duration of action in the body. It is released in

pulses, and its effects on tissues are transient. This means GH’s direct influence
is brief, and its impact on growth and metabolism is short-lived after it is
secreted.

Prolonged Action of Somatomedin C (IGF-I)

●​ When GH is released, it stimulates the liver and other tissues to produce IGF-I
(also known as somatomedin C).
●​ IGF-I is responsible for many of the growth-promoting effects associated with
GH, including bone growth, cartilage development, and muscle growth.
 ●​ IGF-I has a prolonged duration of action compared to GH because it acts in a
more sustained manner. It binds to IGF receptors on cells and can remain active
in tissues for a longer period.
●​ Furthermore, IGF-I’s effects are often delayed, continuing to promote growth and
cellular processes after GH levels have already decreased.

Thus, while GH has short-lived direct effects, IGF-I acts as the mediator for
longer-lasting biological effects, providing the prolonged action associated with
growth and development.

Growth Hormone Actions on Protein Metabolism:

●​ Enhances amino acid uptake and protein synthesis by cells

●​ Reduces protein breakdown
●​ Increases RNA translation and nuclear transcription of DNA to form RNA

Growth Hormone (GH) has a diabetogenic effect, meaning it can impair insulin
function and contribute to insulin resistance. Here's a brief explanation:

●​ Insulin resistance: GH reduces the effectiveness of insulin, leading to a

decreased uptake and utilization of glucose by skeletal muscle and fat cells.
●​ Increased glucose synthesis: GH stimulates the liver to produce more glucose,
further raising blood glucose levels.
●​ Blood glucose increase: This leads to elevated glucose concentrations in the
blood, similar to what is seen in Type 2 Diabetes (DM II).
●​ Compensatory insulin increase: The body compensates by producing more
insulin, but prolonged high GH levels may cause metabolic disturbances
resembling Type 2 diabetes.

Effect on Carbohydrate Metabolism:

●​ Increases plasma glucose concentration

 ●​ Decreases glucose uptake in tissues
●​ Increases gluconeogenesis by the liver
●​ Increases insulin secretion
●​ Glucose sparing (Diabetogenic, Type II)

Disorders of Growth Hormone

1. Hyposecretion

●​ Adults:​

○​ Often part of Panhypopituitarism, where multiple pituitary hormones are

deficient. This can lead to various health issues related to the lack of GH
and other hormones.
●​ Childhood:​

○​ Dwarfism: Stunted growth due to inadequate GH secretion during

childhood. This results in disproportionate development of body parts.
○​ Delayed puberty: Common due to lack of gonadotropic hormones in
cases of panhypopituitarism.
○​ Levi-Lorain Dwarfs: A specific type of dwarfism caused by
Somatomedin C (IGF-1) deficiency, leading to a growth impairment
despite normal GH levels in some cases.
○​ Sexual development: About one-third of individuals with just GH
deficiency may still have normal sexual development.

2. Hypersecretion

●​ Childhood: Gigantism​

○​ Caused by an acidophilic tumor of the anterior pituitary, leading to

excess GH before puberty. This results in excessive growth of all tissues
and bones, making the child grow taller than usual.
○​ Hyperglycemia (high blood sugar) and kyphosis (curved spine) may also
develop due to the prolonged effects of GH excess.
●​ Adults: Acromegaly​
 ○​ Occurs after puberty, when the growth plates have closed, and GH
excess causes thickening of bones (e.g., hands, feet, skull) and growth
of soft tissues.
○​ Common features include enlarged facial features, joint pain, carpal
tunnel syndrome, and increased risk of heart disease, diabetes, and
sleep apnea.

Decreases the rate of glucose utilization throughout the body- Diabetogenic

THYROID HORMONE
Thyroid hormones, primarily thyroxine (T4) and triiodothyronine (T3), are vital for
regulating various physiological processes. Their functions include:

1.​ Metabolism Regulation​

○​ Increase basal metabolic rate (BMR).

○​ Promote energy utilization by stimulating carbohydrate, protein, and fat
metabolism.
2.​ Growth and Development​

○​ Essential for normal growth and skeletal development.

○​ Critical for brain development and maturation, especially during infancy
and childhood.
3.​ Thermogenesis​

○​ Regulate heat production by stimulating oxygen consumption in tissues.

4.​ Cardiovascular Effects​

○​ Increase heart rate and cardiac output.

○​ Enhance sensitivity of the heart to catecholamines (e.g., adrenaline).
5.​ Nervous System Function​

○​ Maintain alertness, reflexes, and emotional stability.

○​ Support development and function of the central and peripheral nervous
systems.
 6.​ Reproductive Health​

○​ Influence menstrual cycles and fertility.

○​ Affect the functioning of reproductive hormones.
7.​ Protein Synthesis and Cell Growth​

○​ Regulate protein turnover and promote cell repair and growth.

8.​ Cholesterol and Lipid Levels​

○​ Facilitate breakdown of cholesterol and regulate lipid metabolism.

Thyroid hormones play a systemic role, ensuring proper function and balance of various
body systems.

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Effects of Thyroid Hormones

1. Carbohydrate Metabolism

●​ Stimulation of all aspects of carbohydrate metabolism:

○​ Increased absorption of carbohydrates from the GIT.
○​ Rapid glucose uptake by cells.
○​ Enhanced gluconeogenesis and glycolysis.
 ○​ Elevated insulin secretion.
●​ Mechanism: These effects result from increased production of cellular metabolic
enzymes.

2. Protein Metabolism

●​ Normal Levels of T3 and T4: Promote protein synthesis (anabolic effect).

●​ High Levels of T3 and T4: Induce protein breakdown (catabolic effect).

3. Plasma and Liver Fats

●​ Decreases plasma cholesterol, phospholipids, and triglycerides.

●​ Mechanism:
○​ Enhances cholesterol secretion into bile for excretion via feces.
○​ Increases LDL receptor expression in the liver, facilitating rapid LDL
clearance.
●​ Hypothyroidism: Results in increased plasma cholesterol and lipids.

4. Vitamin Requirement

●​ Increased demand for vitamins due to their role in synthesizing new enzymes
and co-enzymes.

5. Basal Metabolic Rate (BMR)

●​ Hyperthyroidism: Increases BMR by 60–100%.

●​ Hypothyroidism: Decreases BMR.

6. Body Weight

●​ Hyperthyroidism: Leads to weight loss.

●​ Hypothyroidism: Causes weight gain.
 7. Gastrointestinal Tract

●​ Effects:
○​ Increased appetite and food intake.
○​ Enhanced motility and secretion of digestive juices.
●​ Hyperthyroidism: Excess motility may lead to diarrhea.
●​ Hypothyroidism: Reduced motility can cause constipation.

8. Cardiovascular System (CVS)

●​ Effects on circulation:
○​ Enhanced oxygen utilization and increased metabolic waste production.
○​ Vasodilation and increased blood flow, especially to the skin for heat
dissipation.
○​ Elevated cardiac output.
●​ Effects on the heart:
○​ Increased heart rate and cardiac strength.

9. Growth and Tissue Development

●​ Essential for:
○​ Bone growth and maturation.
○​ Development of skin, hair follicles, and nails.
○​ Childhood brain development.
○​ Deficiency in childhood: Leads to stunted growth and potential mental
retardation.
○​ Excess: Causes accelerated growth initially but premature closure of
growth plates.

10. Nervous System

●​ Normal levels: Vital for brain development, alertness, memory, and reflex speed.
●​ Deficiency from birth: Can lead to severe developmental issues, such as
cretinism.
●​ Excess in adults: Causes increased excitability, irritability, and tremors.
 11. Effects on Muscle

●​ Hyperthyroidism:
○​ Muscle overreactivity and fine tremors.
○​ Severe cases cause muscle weakness (thyrotoxic myopathy).
●​ Hypothyroidism:
○​ Muscle sluggishness and delayed relaxation after contraction.

12. Reproductive System

●​ Females:
○​ Required for follicular development and ovulation.
○​ Hyperthyroidism: May cause oligomenorrhea (scanty periods).
○​ Hypothyroidism: Can lead to menorrhagia (heavy bleeding) or
polymenorrhea (frequent periods).
●​ Males:
○​ Required for normal spermatogenesis.
○​ Hyperthyroidism: May lead to impotence.
○​ Hypothyroidism: Results in reduced libido.

13. Effects on Sleep

●​ Hyperthyroidism: Difficulty sleeping due to excitability.

●​ Hypothyroidism: Causes excessive sleepiness.

14. Interaction with Other Endocrine Glands

●​ Thyroid hormones stimulate secretion of other hormones and increase tissue

demand for them:
○​ Insulin.
○​ Parathyroid hormone.
○​ ACTH and glucocorticoids.

Effects of Thyroid Hormones on Fat Metabolism (Briefly)

1.​ Decreased Plasma Lipids:​

○​ Reduces levels of cholesterol, phospholipids, and triglycerides in plasma.

2.​ Cholesterol Regulation:​

○​ Increases cholesterol excretion into bile and feces.

○​ Upregulates LDL receptors in the liver, facilitating rapid removal of LDL
from plasma.
3.​ Fat Mobilization:​

○​ Enhances lipolysis (breakdown of fat) in adipose tissue.

○​ Increases free fatty acid levels in the blood.
4.​ Energy Utilization:​

○​ Promotes oxidation of fatty acids for energy production.

5.​ Clinical Implications:​

○​ Hypothyroidism: Leads to increased plasma cholesterol and

triglycerides, predisposing to atherosclerosis.
○​ Hyperthyroidism: Causes increased fat breakdown and utilization,
leading to fat loss.
 Difference Between Hypothyroidism and Hyperthyroidism

Aspect Hypothyroidism Hyperthyroidism

Thyroid Hormone Decreased (low T3 and T4) Increased (high T3 and T4)
Levels

Metabolic Rate Decreased basal metabolic rate (BMR) Increased BMR (60–100% above normal)

Body Weight Increased (due to slower metabolism) Decreased (due to rapid metabolism)

Energy Levels Fatigue, lethargy Hyperactivity, restlessness

Appetite Decreased Increased

GI Symptoms Constipation Diarrhea

Skin Dry, coarse, and cold skin Warm, moist, and sweaty skin

Hair Hair thinning or hair loss Thin, fine hair; sometimes hair loss

Heart Rate Bradycardia (slow heart rate) Tachycardia (fast heart rate)

Temperature Tolerance Intolerance to cold Intolerance to heat

Mental State Depression, mental sluggishness Irritability, anxiety, nervousness

Sleep Patterns Excessive sleepiness (somnolence) Difficulty sleeping (insomnia)

 Muscle Function Weakness and delayed relaxation of Muscle weakness and tremors (thyrotoxic
muscles myopathy)

Menstrual Cycle Heavy, irregular periods (menorrhagia, Scanty or irregular periods

polymenorrhea) (oligomenorrhea)

Cholesterol Levels Elevated (risk of atherosclerosis) Decreased

Growth in Children Stunted growth, delayed development Accelerated growth but early growth plate
closure

Exophthalmos Not present Often present (bulging eyes, in Graves'

disease)

Thyroid Gland May be enlarged (goiter) or atrophied Enlarged gland (goiter, often diffuse)

Causes

●​ Hypothyroidism: Autoimmune diseases (e.g., Hashimoto’s thyroiditis), iodine

deficiency, thyroidectomy, or radiation.
●​ Hyperthyroidism: Graves’ disease, toxic multinodular goiter, or thyroid
adenoma.
 Treatment

●​ Hypothyroidism: Thyroid hormone replacement (e.g., levothyroxine).

●​ Hyperthyroidism: Antithyroid medications, radioactive iodine therapy, or
surgery.

Myxedema

Myxedema is a severe form of hypothyroidism characterized by non-pitting edema,

thickened skin, and swelling, especially in the face and extremities, due to
mucopolysaccharide buildup in tissues. It can lead to myxedema coma, a
life-threatening condition requiring urgent thyroid hormone replacement.

Features of Myxedema

1.​ Puffy face, hands, and feet (non-pitting edema).

2.​ Dry, coarse, and thickened skin.
3.​ Sparse hair and loss of outer eyebrows.
4.​ Hoarseness and slow speech.
5.​ Cold intolerance and lethargy.
6.​ Severe cases: Myxedema coma (hypothermia, confusion, bradycardia).
 Calcium phosphate regulation
Calcium is tightly regulated in the extracellular fluid (ECF) because it
plays critical roles in various physiological processes. Deviations from
the normal range (9.4 mg/dL or 2.4 mmol/L) can lead to severe
complications.
 Distribution of
Phosphate in the Human Body

●​ Bones and Teeth: ~85%

○​ Phosphate is a major component of hydroxyapatite, which gives bones
and teeth their structure and strength.
●​ Intracellular Fluid (ICF): ~14%
○​ Phosphate is essential for energy storage and metabolism (e.g., ATP,
nucleic acids).
●​ Extracellular Fluid (ECF) and Plasma: ~1%
○​ Phosphate is present as inorganic phosphate (Pi) and is involved in
buffering systems in the blood.

This distribution ensures phosphate plays critical roles in bone health, cellular
metabolism, and maintaining acid-base balance.

Inorganic Phosphate in the Extracellular Fluid (ECF)

1.​ Phosphate Forms:​

○​ HPO₄²⁻ (Hydrogen Phosphate):​

■​ Normal concentration: 1.05 mmol/L.

■​ Effect of pH: As the pH of the ECF increases (alkaline conditions),
the concentration of HPO₄²⁻ increases, and the concentration of
H₂PO₄⁻ decreases.
○​ H₂PO₄⁻ (Dihydrogen Phosphate):​
 ■​ Normal concentration: 0.26 mmol/L.
■​ Effect of pH: In acidic conditions (low pH), H₂PO₄⁻ predominates,
and the concentration of HPO₄²⁻ decreases.
2.​ Total Phosphate Concentration:​

○​ In adults: 3-4 mg/dL.

○​ In children: 4-5 mg/dL.

Phosphate levels in the ECF are influenced by pH, and they are crucial for maintaining
acid-base balance, as well as participating in other physiological functions.

Changing levels of PO4 in ECF below to 2-3 times normal ; ↓ no major immediate
effects ▪ Slight ↑ or ↓ of calcium ions ↓ ; extreme immediate physiological effects

Effects of Hypocalcemia on the Nervous System

●​ Increased Neuronal Excitability:​

○​ Low calcium levels (hypocalcemia) increase the permeability of neuronal

membranes to sodium ions, making it easier to initiate action potentials.
●​ Tetanic Muscle Contraction:​

○​ At plasma calcium concentrations <50% normal, tetany (muscle spasms)

can occur, often beginning at calcium levels of 6 mg/dL (35% below
normal).
●​ Seizures:​

○​ Increased excitability in the brain can lead to seizures, as the brain's

neurons become more easily activated.
●​ Lethal Levels:​

○​ Calcium levels <4 mg/dL (1 mmol/L) are considered lethal and can result
in severe neuromuscular and cardiac dysfunction.

In summary, hypocalcemia increases nervous system excitability, causing conditions

like tetany and seizures due to the lowered threshold for action potential initiation.

Effects of Hypercalcemia on the Nervous System and Other Systems

●​ Nervous System Depression:​

 ○​ Calcium Levels >12–15 mg/dL: Results in nervous system depression,
with symptoms like confusion, lethargy, reduced reflexes, and even coma
at higher levels.
○​ Symptoms usually appear at ≥ 12 mg/dL (3.0 mmol/L).
●​ Cardiac Effects:​

○​ Bradycardia (slow heart rate) and short QT interval are common.

○​ Cardiac arrest may occur at 15 mg/dL (3.75 mmol/L).
●​ Gastrointestinal Effects:​

○​ Anorexia, constipation, and abdominal cramps are frequent.

●​ Renal and Endocrine Effects:​

○​ Polyuria (excessive urine production) and polydipsia (excessive thirst)

due to impaired renal concentrating ability.
○​ Increased risk of kidney stones (renal calculi), especially with high
phosphate levels.
○​ Pancreatitis and peptic ulcers may occur.
●​ Skeletal Effects:​

○​ Bone pain and pathological fractures due to calcium resorption from

bones.
●​ Phosphate Crystals:​

○​ At calcium levels >17 mg/dL, calcium phosphate crystals may form in

tissues.

Phosphate Absorption and Excretion

●​ Absorption in the Gut:​

○​ Most ingested phosphate is absorbed in the gastrointestinal tract.

●​ Excretion in Urine:​

○​ Phosphate is excreted in urine after absorption.

○​ Overflow mechanism: Critical phosphate concentration is ≤ 1 mmol/L,
where phosphate reabsorption is maximized when levels are too low.
●​ Regulation by PTH:​
 ○​ Parathyroid hormone (PTH) regulates phosphate excretion by
decreasing reabsorption in the kidneys.

Hypercalcemia impacts multiple organ systems, leading to severe disturbances in

neuromuscular function, cardiac rhythm, kidney function, and bone health.
 Bone Composition and Formation Overview

1. Bone Composition

●​ Organic (33%)​

○​ Bone Cells:
■​ Osteoblasts: Responsible for bone formation.
■​ Osteoclasts: Involved in bone resorption.
■​ Osteocytes: Mature osteoblasts embedded within the bone matrix.
○​ Collagen fibers: Primarily Type I collagen.
○​ Ground substance: Includes proteoglycans and glycoproteins.
○​ Osteoid: Newly secreted organic bone matrix.
●​ Inorganic (67%)​

○​ Hydroxyapatite (Ca₁₀(PO₄)₆(OH)₂): 65% of bone mass.

○​ Bone salts: Mainly calcium and phosphate crystals.

2. Hydroxyapatite Precipitation Control

●​ Despite high levels of calcium and phosphate ions in the extracellular fluid
(ECF), hydroxyapatite does not precipitate in tissues except bone.
●​ Pyrophosphate acts as an inhibitor, preventing premature precipitation of
hydroxyapatite.

3. Bone Formation Process

1.​ Osteoblast Activity:​

○​ Active osteoblasts secrete collagen monomers and ground substance.

○​ These monomers form a polymerized osteoid, an organic matrix.
○​ Calcium phosphate salts (CaPO₄) are deposited in the osteoid,
mineralizing the matrix.
2.​ Collagen and Mineralization:​

○​ Hydroxyapatite crystals form along the collagen fibers, contributing to the

bone's mineral structure.
○​ Some calcium salts remain amorphous (non-crystalline), which are
readily exchangeable.
3.​ Osteocyte Formation:​

○​ As osteoblasts become entrapped in the osteoid, they mature into

osteocytes.

4. Canaliculi

●​ Canaliculi: Tiny channels within bone units that contain fluid.

●​ These channels traverse through mineralized bone, allowing osteocytes to
maintain communication and transfer calcium to the extracellular fluid.

5. Bone Formation and Resorption Regulation

●​ Bone Resorption Mechanisms:​

○​ Osteocytic osteolysis: Rapid, transient calcium transfer from canaliculi to

extracellular fluid without decreasing bone mass.
○​ Osteoclastic resorption: Slow and sustained resorption, where
osteoclasts remove the bone matrix and diminish bone mass. Both
processes are stimulated by parathyroid hormone (PTH).
●​ Calcium Phosphate Precipitation:​

○​ Calcium and phosphate precipitate out of solution if their solubility product

(Ksp) is exceeded: Ksp=[Ca2+]3[PO43−]2Ksp = [Ca^{2+}]^3[PO_4^{3-}]^2
○​ PTH helps maintain calcium levels in plasma, keeping calcium levels
around 6-7 mg/dL by regulating bone resorption.

6. Osteocytic Osteolysis

●​ Involves rapid calcium transfer via osteocytes from canaliculi to extracellular fluid.
●​ Does not decrease bone mass and primarily affects newer bone crystals.

7. Bone Resorption by Osteoclasts

●​ Osteoclasts are responsible for resorbing bone.

 ●​ Bone resorption involves not just extracting calcium but also destroying the bone
matrix, leading to a decrease in bone mass.

8. Bone Remodeling Process

●​ Endocrine signals activate resting osteoblasts, which then produce paracrine

signals to stimulate osteoclasts and their precursors.
●​ Osteoclasts resorb mineralized bone at the targeted site.
●​ After bone resorption, macrophages clean up the debris.
●​ Osteoblasts and their precursors generate a new matrix that is subsequently
mineralized.
●​ The new bone replaces the previously resorbed bone.

This process of bone remodeling ensures that bone structure remains dynamic and
adaptable, responding to mechanical stresses and metabolic demands.

Calcium Metabolism and Disorders Overview

Calcium Salt Precipitation

●​ Arteriosclerosis: Calcium salts may precipitate in arterial walls during

arteriosclerosis, causing arteries to become bone-like tubes.
●​ Tissue Degeneration: Calcium salts also deposit in degenerating tissues or old
blood clots.
●​ Inhibitor Factors: When inhibitory factors that normally prevent precipitation
disappear from tissues, calcium salts can form crystals, contributing to
pathological calcification.

Fluctuations in Extracellular Calcium

●​ Fluctuations in extracellular calcium levels (Ca++) typically last 30-60 minutes

before returning to normal.
●​ Readily Exchangeable Calcium: Calcium exists in forms like CaHPO₄ in bone,
which can be readily exchanged with the extracellular fluid.

Hormonal Regulation of Calcium Metabolism

1.​ Parathyroid Hormone (PTH):​

 ○​ Secreted by parathyroid glands, PTH is the primary regulator of
calcium metabolism.
○​ Inversely related to plasma calcium levels: As calcium levels drop, PTH
secretion increases.
○​ PTH Action:
■​ Increases calcium release from bones.
■​ Enhances calcium reabsorption in the kidneys.
■​ Facilitates activation of Vitamin D.
2.​ Vitamin D:​

○​ Increases calcium and phosphate absorption from the intestines.

○​ Synthesized from a cholesterol derivative when the skin is exposed to
sunlight.
○​ Inadequate dietary intake can lead to deficiency.
○​ Activation Process:
■​ Vitamin D must be activated first by the liver and then by the
kidneys before it can exert effects on calcium and phosphate
absorption.
3.​ Vitamin D Actions:​

○​ Intestine:
■​ Increases Ca++ and phosphate absorption.
○​ Kidneys:
■​ Increases Ca++ and phosphate reabsorption (weak effect).
○​ Bone:
■​ Increases mineralization indirectly.
■​ Increases bone resorption directly.
■​ Without vitamin D, PTH’s effect on bone resorption is significantly
reduced.
4.​ Calcitonin:​

○​ Secreted by parafollicular cells of the thyroid gland, it is released when

calcium levels exceed 10% above normal.
○​ Actions:
■​ Decreases osteoclast activity (rapid effect).
■​ Decreases osteoclast formation (prolonged effect).
■​ Minor effects on calcium handling in the kidneys and intestines.
○​ Function: Calcitonin's role is minor compared to PTH and Vitamin D,
primarily playing a role during hypercalcemia.
 Calcium Disorders

1.​ Hyperparathyroidism:​

○​ Characterized by hypercalcemia (elevated calcium) and

hypophosphatemia (low phosphate).
○​ Often due to excessive secretion of PTH, leading to increased calcium
release from bones.
2.​ Hypoparathyroidism:​

○​ Characterized by hypocalcemia (low calcium) and hyperphosphatemia

(high phosphate).
○​ Results from insufficient PTH production, leading to low calcium levels in
the blood.
3.​ Vitamin D Deficiency:​

○​ Children: Leads to rickets, characterized by weakened bones and

skeletal deformities.
○​ Adults: Causes osteomalacia, resulting in soft, fragile bones.

This system of hormonal regulation ensures that calcium levels remain tightly controlled,
impacting bone health, muscle function, and various metabolic processes.
 Glucocorticoids Overview

Regulation of Glucocorticoids

●​ CRH (Corticotropin-releasing hormone) from the hypothalamus is the primary

regulator of ACTH (Adrenocorticotropic hormone) secretion.
●​ ACTH is released from the anterior pituitary and stimulates the synthesis and
secretion of cortisol.
●​ Both CRH and ACTH are secreted in pulses, which helps regulate the body's
response to stress.

Types of Glucocorticoids

●​ Cortisol: The primary glucocorticoid.

●​ Corticosterone: A glucocorticoid similar to cortisol.
●​ Cortisone: A synthetic glucocorticoid, as potent as cortisol.
●​ Prednisone: A synthetic glucocorticoid, 4x more potent than cortisol.
●​ Methylprednisolone: A synthetic glucocorticoid, 5x more potent than cortisol.
●​ Dexamethasone: A synthetic glucocorticoid, 30x more potent than cortisol.
Functions of Cortisol

1.​ Gluconeogenesis Stimulation:​

○​ Increases enzyme activity in the liver to produce glucose.

○​ Promotes the mobilization of amino acids from extra-hepatic tissues.
○​ Reduces glucose utilization by cells, contributing to adrenal diabetes.
○​ May lead to increased plasma insulin levels.
2.​ Protein Catabolism:​

○​ Decreases protein synthesis in all tissues except the liver, leading to high
plasma protein levels.
3.​ Fat Mobilization:​

○​ Promotes the mobilization of fatty acids from adipose tissues.

○​ Increases the oxidation of fatty acids.
4.​ Stress Response:​

○​ Essential for coping with stress, as without glucocorticoids, the body

cannot manage even mild stress.
○​ Permissive effect: Glucocorticoids facilitate the action of glucagon and
catecholamines during stress.
5.​ Circulation and Blood Pressure:s​

○​ Mineralcorticoid effect: Cortisol has a weak mineralocorticoid effect

(similar to aldosterone), affecting blood pressure regulation.
○​ Sensitizes arterioles to the action of noradrenaline, promoting
vasoconstriction.
○​ Decreases capillary permeability, contributing to fluid retention.
6.​ Immune System Suppression:​

○​ Reduces the production of eosinophils and lymphocytes.

○​ Suppresses the lymphoid tissue, leading to a decrease in T cell and
antibody production, thereby decreasing immunity.
○​ This effect is useful in reducing organ rejection during transplant
surgeries but can be fatal in diseases like tuberculosis.
7.​ Calcium Balance:​

○​ Cortisol causes a negative calcium balance, and long-term use of

high-dose cortisol can lead to bone loss and osteoporosis.
8.​ Developmental Functions:​

○​ Fetal Organ Maturation: Cortisol regulates the maturation of fetal organs.

○​ Surfactant Synthesis: Cortisol stimulates the production of surfactant in
the lungs, a phospholipid that helps maintain alveolar surface tension.

Cushing’s Syndrome

●​ Cushing's Syndrome is a condition caused by excess glucocorticoids in the

body, often from long-term exposure to high levels of cortisol.

Causes:

1.​ Pharmacologic: Use of synthetic glucocorticoids.

2.​ Pituitary Adenoma: Accounts for 75-90% of cases, leading to excessive ACTH
secretion.
3.​ Adrenal Adenoma or Carcinoma: Tumors in the adrenal gland can secrete
cortisol independently of ACTH.
4.​ Ectopic ACTH Secretion: Tumors in places other than the pituitary (e.g., lungs)
secrete ACTH, overstimulating the adrenal glands.
 Differences between Cushing's Syndrome and Addison's Disease

Both Cushing's syndrome and Addison's disease are disorders related to the adrenal
glands, but they result from opposite conditions concerning glucocorticoid levels.

Cushing's Syndrome

●​ Cause:​

○​ Overproduction of cortisol.
○​ Often due to pituitary adenoma (Cushing's disease), adrenal tumors, or
ectopic ACTH production (tumors outside the pituitary).
○​ Can also result from long-term use of synthetic glucocorticoids (e.g.,
prednisone).
●​ Symptoms:​

○​ Weight gain (especially around the abdomen, face, and neck; "moon
face" and "buffalo hump").
○​ Hypertension (high blood pressure).
○​ Hyperglycemia (can lead to diabetes).
○​ Muscle weakness and atrophy.
○​ Thin skin and easy bruising.
○​ Osteoporosis (bone loss).
○​ Striae (purple stretch marks) on the skin.
○​ Mood changes: Anxiety, irritability, and depression.
○​ Increased susceptibility to infections due to immune suppression.
●​ Laboratory Findings:​

○​ High cortisol levels.

○​ High ACTH in pituitary adenoma or low ACTH in adrenal tumors.
●​ Treatment:​

○​ Surgery to remove the tumor or reduce cortisol production.

○​ Medications to block cortisol synthesis if surgery is not possible.

Addison's Disease

●​ Cause:​

○​ Underproduction of cortisol and aldosterone.

 ○​ Typically caused by autoimmune destruction of the adrenal glands
(most common).
○​ Can also result from tuberculosis, adrenal hemorrhage, or metastatic
cancer affecting the adrenal glands.
●​ Symptoms:​

○​ Fatigue and weakness.

○​ Hypotension (low blood pressure), particularly after standing (orthostatic
hypotension).
○​ Hyperpigmentation (darkening of the skin, especially in areas exposed to
friction or sun).
○​ Salt cravings due to low aldosterone levels.
○​ Weight loss and loss of appetite.
○​ Nausea, vomiting, and diarrhea.
○​ Hypoglycemia (low blood sugar).
○​ Electrolyte imbalances: Hyponatremia (low sodium), hyperkalemia
(high potassium).
●​ Laboratory Findings:​

○​ Low cortisol levels.

○​ High ACTH due to lack of feedback inhibition.
○​ Low sodium and high potassium due to aldosterone deficiency.
●​ Treatment:​

○​ Hormone replacement therapy (cortisol and sometimes aldosterone)

with synthetic glucocorticoids (hydrocortisone) and mineralocorticoids.
○​ Stress dose steroids during illness or surgery to prevent an adrenal
crisis.

Summary:

●​ Cushing's Syndrome: Overproduction of cortisol, leading to symptoms like

weight gain, high blood pressure, and glucose intolerance.
●​ Addison's Disease: Underproduction of cortisol and aldosterone, leading to
symptoms like fatigue, low blood pressure, hyperpigmentation, and electrolyte
imbalances.

Regulation of Cortisol Secretion:

Cortisol secretion is primarily controlled by the hypothalamic-pituitary-adrenal
(HPA) axis, with a cascade of signals from the hypothalamus, pituitary gland, and
adrenal cortex. Here's a breakdown:

1.​ Abnormal CRH Release:​

○​ The hypothalamus releases Corticotropin-Releasing Hormone (CRH),

which stimulates the anterior pituitary to release ACTH
(Adrenocorticotropic Hormone).
2.​ Pituitary Adenoma (Cushing’s Disease):​

○​ A pituitary adenoma can result in excessive ACTH secretion, leading

to overproduction of cortisol, which is known as ACTH-dependent
Cushing’s syndrome.
3.​ Ectopic Secretion of ACTH:​

○​ Some non-pituitary tumors (e.g., lung cancers) can produce ACTH

independently of the pituitary, causing ACTH-dependent Cushing's
syndrome.
4.​ Adrenal Cortical Adenoma:​

○​ ACTH-independent Cushing's syndrome occurs when there is

overproduction of cortisol by the adrenal glands themselves (due to
adrenal tumors), without the influence of ACTH.
5.​ Excessive Administration of Glucocorticoids:​

○​ Prolonged use of synthetic glucocorticoids (e.g., prednisone) can

mimic Cushing's syndrome, leading to the same symptoms as those
seen with endogenous cortisol overproduction.

Dexamethasone Test (Cushing’s Syndrome Diagnosis):

●​ ACTH-dependent Cushing’s syndrome (Pituitary adenoma):​

○​ Low doses of dexamethasone usually do not suppress ACTH

secretion in ACTH-secreting pituitary adenoma or
hypothalamic-pituitary dysfunction.
○​ High levels of dexamethasone can eventually suppress ACTH
secretion.
●​ ACTH-independent Cushing’s syndrome (Adrenal overproduction):​
 ○​ In primary adrenal overproduction, there will be low or undetectable
levels of ACTH.
○​ This can sometimes lead to an incorrect diagnosis because some
ACTH-secreting tumors may still respond to high doses of
dexamethasone with suppressed ACTH secretion.

Mineralocorticoids (Aldosterone) and Its Effects:

●​ Aldosterone is the primary mineralocorticoid, with 90% of its activity being

mineralocorticoid in nature.
●​ Normal concentration: 6 ng/100ml.
●​ Secretory rate: 0.15 mg/day.
●​ Aldosterone's mineralocorticoid activity is 3000 times greater than cortisol,
though cortisol is 2000 times more abundant.

Effects on Plasma Potassium:

1.​ Excess Aldosterone (Hyperaldosteronism):​

○​ Hypokalemia (low potassium).

○​ Muscular weakness due to reduced potassium levels.
2.​ Deficient Aldosterone (Hypoaldosteronism):​

○​ Hyperkalemia (high potassium).

○​ Cardiac toxicity (e.g., arrhythmias).

Effects on Hydrogen Ion Concentration:

●​ Alkalosis due to the excretion of H+ ions by intercalated cells in the cortical

collecting tubules of the kidney.

Effects on Salivary and Sweat Glands:

●​ Increases sodium (Na+) reabsorption and potassium (K+) secretion in the

salivary and sweat glands.

Renin-Angiotensin-Aldosterone System (RAAS):

●​ Increased potassium concentration in the extracellular fluid stimulates the

release of renin from the kidneys.
●​ Renin activates the RAAS, which leads to increased aldosterone secretion
from the adrenal glands.
 ●​ Aldosterone acts on the kidneys to increase sodium reabsorption, and
increase potassium and hydrogen ion secretion, helping to regulate fluid
balance and blood pressure.

Conn's Syndrome (Primary Hyperaldosteronism):

●​ Cause: Zona glomerulosa tumor (adrenal adenoma) that secretes excess

aldosterone.​

●​ Effects:​

○​ Slight increase in ECF volume and plasma sodium.

○​ Hypokalemia (low potassium), leading to symptoms like muscle
paralysis.
○​ Alkalosis due to excess H+ ion secretion.
○​ Diagnosis: Decreased plasma renin concentration.
●​ Treatment: Surgical removal of the tumor.​

Addison's Disease:

●​ Cause: Failure of the adrenal cortex to secrete adrenocortical hormones

(cortisol, aldosterone, etc.), leading to adrenal insufficiency.​

○​ Often caused by autoimmune atrophy, tuberculous destruction, or

metastasis affecting the adrenal glands.
●​ Secondary Addison's Disease:​

○​ Due to pituitary dysfunction, leading to insufficient ACTH production

and hence low cortisol and aldosterone levels.
○​ Atrophy of adrenal glands due to lack of ACTH stimulation.
●​ Glucocorticoid Deficiency Effects:​

○​ Reduced gluconeogenesis → hypoglycemia.

○​ Decreased mobilization of fats and proteins → depressed
metabolism.
○​ Increased sensitivity to stress; mild infections can be
life-threatening.

Low Aldosterone Effects (Mineralocorticoid Deficiency):

 ●​ Failure of K+ and H+ secretion due to lack of aldosterone.
●​ Hyponatremia (low sodium) and hypovolemia leading to reduced cardiac
output and blood pressure, potentially resulting in shock.
●​ Hyperkalemia causing cardiac toxicity (e.g., arrhythmias).
●​ Mild acidosis due to impaired H+ ion secretion.

Hyperpigmentation in Addison's Disease:

●​ Individuals with Addison’s disease often experience hyperpigmentation

(darkening of the skin) and mucous membranes due to increased
production of ACTH (which shares a precursor with melanocyte-stimulating
hormone).

Treatment for Addison’s Disease:

●​ Glucocorticoids and mineralocorticoids are administered orally to replace

the deficient hormones, ensuring the patient maintains proper metabolic
balance and blood pressure.
CONTROL OF METABOLIC REGULATION THORUGH INSULIN

Here's the structured response you requested:

Physiological Anatomy of the Pancreas

1.​ Acini​

○​ Secrete digestive juices.

2.​ Islets of Langerhans​

○​ Beta cells: Insulin and Amylin.

○​ Alpha cells: Glucagon.
○​ Delta cells: Somatostatin.
○​ PP cells: Pancreatic polypeptide.

Pancreatic Hormones

1.​ Amylin​

○​ Secreted in parallel with insulin, though its function remains unclear.

○​ Inhibits insulin secretion.
2.​ Somatostatin​

○​ Prevents excessive plasma levels of nutrients.

○​ Decreases secretion of insulin, glucagon, and somatostatin itself.
3.​ Pancreatic Polypeptide​

○​ Self-regulates pancreatic secretion activities.

Insulin

1.​ Chemistry and Synthesis​

○​ Half-life: 6 minutes.
○​ Destroyed by insulinase.
○​ Anabolic hormone:
■​ Increases cellular uptake of glucose, fatty acids, and amino acids.
■​ Enhances their conversion into glycogen, triglycerides, and proteins.
2.​ Secretion Stimuli​

○​ Increased blood glucose concentration (primary stimulus).

○​ Increased secretion during the absorptive state.
3.​ Insulin-Dependent Tissues​

○​ Adipose tissue.
○​ Resting skeletal muscle.
○​ Note: Glucose can enter working muscle without insulin.
4.​ Insulin-Independent Tissues​

○​ Nervous tissue.
○​ Kidney tubules.
○​ Intestinal mucosa.
○​ Red blood cells.
○​ Beta-cells of the pancreas.

Principal Actions of Insulin

1.​ Rapid (Seconds)​

○​ Increases transport of glucose, amino acids, and K+ into insulin-sensitive cells.

2.​ Intermediate (Minutes)​

○​ Stimulates protein synthesis and inhibits protein degradation.

○​ Activates glycolytic enzymes and glycogen synthase.
○​ Inhibits phosphorylase and gluconeogenic enzymes.
3.​ Delayed (Hours)​

○​ Increases mRNAs for lipogenic and other enzymes.

Effects of Insulin

On Carbohydrate Metabolism

1.​ Muscles​

○​ Resting state: Slightly permeable to glucose; uses free fatty acids for energy.
○​ Heavy/moderate exercise: Glucose uptake increases due to muscle contraction (low insulin
levels sufficient).
○​ Few hours after meals: High insulin levels → Increased glucose uptake and energy use;
excess glucose stored as glycogen.
2.​ Liver​

○​ After Meals:​

■​ Increased glucose uptake.

■​ Inactivates glucose phosphorylase (glycogen breakdown).
■​ Increases glucokinase activity (glucose phosphorylation).
■​ Activates glycogen synthase (glycogen synthesis).
■​ Converts excess glucose into fatty acids → Triglycerides → LDL → Stored as fat in
adipose tissue.
■​ Inhibits gluconeogenesis by decreasing liver enzyme activities and reducing amino
acid release.
 ○​ Between Meals:​

■​ Low insulin levels activate glucose phosphorylase and glucose phosphatase,

reversing storage processes.
3.​ Brain​

○​ Brain cells use glucose for energy and are permeable to glucose without insulin.
○​ Hypoglycemic shock occurs when blood glucose levels drop to 20-50 mg/100ml.

On Fat Metabolism

1.​ After Meals​

○​Promotes fatty acid synthesis and storage.

○​Activates lipoprotein lipase in adipose tissue (triglycerides → fatty acids for absorption).
○​Inhibits hormone-sensitive lipase (prevents fatty acid release).
○​Increases glucose transport into fat cells, converted to α-glycerol phosphate → Combines
with fatty acids to form triglycerides.
2.​ Between Meals​

○​ Activates hormone-sensitive lipase, releasing fatty acids for energy.

On Protein Metabolism

1.​ Promotes protein synthesis and storage:

○​ Uptake of amino acids.
○​ Increases transcription and translation.
○​ Inhibits protein catabolism and gluconeogenesis in the liver.

Special Role in Potassium Regulation

●​ Insulin increases Na+/K+-ATPase activity, pumping K+ into cells.

●​ This effect is utilized in treating hyperkalemia (life-threatening high potassium levels).

Let me know if you'd like any further details!

Here’s the breakdown of Effects of Insulin Deficiency:

Increased Use of Fat for Energy

1.​ Lipolysis​

○​ Breakdown of stored fat → Release of free fatty acids.

 ○​ Activation of hormone-sensitive lipase in fat cells.
2.​ Ketosis and Acidosis​

○​ Excess fat usage leads to increased beta-oxidation of fatty acids.

○​ Formation of ketone bodies:
■​ Acetoacetic acid
■​ β-hydroxybutyric acid
■​ Acetone
○​ Results in ketosis, which can progress to diabetic ketoacidosis, leading to coma and death.
3.​ Cholesterol and Phospholipids​

○​ Increased production, which raises the risk of atherosclerosis.

Protein Depletion and Increased Plasma Amino Acids

1.​ Protein Catabolism​

○​ Increased breakdown of proteins.

○​ Halted protein synthesis.
2.​ Amino Acid Utilization​

○​Excess amino acids used for:

■​ Energy production
■​ Substrates for gluconeogenesis (formation of glucose from non-carbohydrate
sources).
3.​ Urea Excretion​

○​ Enhanced degradation of amino acids leads to increased urea excretion in the urine.
4.​ Effects​

○​ Extreme protein wasting.

These effects are commonly observed in uncontrolled diabetes due to insulin deficiency, and they contribute
to various complications. Let me know if you need any more details or further elaboration!

Uhh
 Here’s the summary of Role of Insulin and Glucagon in
Metabolism:

Insulin

●​ Primary Function: Promotes carbohydrate utilization for energy while suppressing fat
utilization.
●​ Secretion: High glucose levels stimulate insulin secretion, leading to:
○​ Carbohydrate (CHO) usage for energy instead of fat.
○​ Excess glucose stored as:
■​ Liver glycogen
■​ Liver fat
■​ Muscle glycogen

Effects of Hypoglycemia on the Nervous System

1.​ Limited Neural Carbohydrate Reserves​

○​ Initial Symptoms (Autonomic discharge): Palpitations, sweating, nervousness.

○​ Severe Symptoms (Neuroglycopenic): Hunger, confusion, lethargy,
convulsions, and coma.
○​ Prolonged hypoglycemia can cause permanent intellectual impairment.
2.​ Treatment: Prompt glucose administration reverses symptoms rapidly.​
 Compensation for Hypoglycemia

1.​ Inhibition of Insulin Secretion:​

○​ Occurs at around 80 mg/dL glucose.

2.​ Counter-Regulatory Hormones:​

○​ Glucagon and Epinephrine: Increase glycogenolysis and gluconeogenesis.

○​ Growth Hormone and Cortisol: Decrease glucose utilization in peripheral
tissues.
3.​ Key Regulators:​

○​ Glucagon and Epinephrine are primary regulators; other hormones play

supplementary roles.

Glucagon

●​ Postabsorptive State: Mobilizes energy molecules; known as a hyperglycemic

hormone.
●​ Half-Life: 3-6 minutes.

Effects on Glucose Metabolism

1.​ Stimulates glycogenolysis (breakdown of glycogen into glucose).

2.​ Activates adenylyl cyclase in hepatic cell membranes.
3.​ Increases gluconeogenesis and amino acid uptake in the liver.
4.​ Inhibits glycolysis (breakdown of glucose).

Effects on Lipid Metabolism

1.​ Stimulates lipolysis (breakdown of fat) and ketogenesis (production of ketone bodies).
2.​ Activates adipose cell lipase.
3.​ Inhibits triglyceride storage in the liver.

Other Functions

1.​ Increases cardiac strength.

2.​ Enhances kidney blood flow.
3.​ Increases bile secretion.
4.​ Inhibits gastric acid secretion.
 Importance of Maintaining Blood Glucose Levels

1.​ Osmotic Pressure: High glucose can dehydrate cells.

2.​ Urinary Glucose Loss: Excess glucose leads to glucose loss in urine.
3.​ Osmotic Diuresis: Loss of water and electrolytes via kidneys.
4.​ Long-Term Effects: High glucose damages tissues, increasing the risk of:
○​ Heart attack
○​ Stroke
○​ Renal disease
○​ Blindness

This outline explains how insulin and glucagon work together to regulate blood glucose levels
and their importance in maintaining overall metabolic balance. Let me know if you'd like further
details!