Lecture_17__Endocrine_II

Lecture Overview

• Lecture #17: Endocrine II

  • Topics Covered: Pineal Gland, Parathyroid Gland, Thyroid, Pancreas

Pineal Gland

• Location: Small gland hanging from the roof of the third ventricle.

• Function: Secretes melatonin which is involved in:

  • Regulation of sleep cycle

  • Circadian (daily) rhythms such as temperature and appetite

  • Timing of sexual maturation and puberty

• Melatonin Receptors: Located in the brain, specifically in the anterior pituitary and hypothalamus.

Melatonin Regulation

• Secretion:

  • Decreases during bright light (sunlight)

  • Increases in the dark (at night)

• Role: Sometimes referred to as nature's sleeping pill.

• Questions Raised: What factors prevent us from sleeping at night?

Parathyroid Glands

• Location: Four to eight tiny glands embedded in the posterior thyroid.

• Main Function: Contain parathyroid cells that secrete parathyroid hormone (PTH), also known as parathormone.

• Importance of PTH: Most important hormone in maintaining calcium (Ca²+) homeostasis.

Parathyroid Regulation

• Low Blood Ca²+ (Hypocalcemia):

  • When blood calcium levels decrease, PTH is released, which leads to activation processes such as bone breakdown and calcium reabsorption.

• Inhibition of PTH Release: Occurs when blood calcium levels are high, which also activates vitamin D processes that promote Ca²+ absorption.

Parathyroid Hormone Imbalance

• Hyperparathyroidism (Tumor):

  • Characterized by excess PTH leading to softening and deformity of bones (osteoporosis) and can contribute to kidney stone formation.

  • Causes depression of the nervous system due to elevated calcium levels.

• Hypoparathyroidism:

  • Can result from gland trauma or removal leading to low blood calcium levels, causing membrane depolarization and muscular tetanus, which can lead to respiratory paralysis or death.

Thyroid Gland Structure

• Location: Situated in the neck, connected by a median mass known as the isthmus, comprising right and left lobes.

• Components:

  • Follicular cells produce glycoprotein thyroglobulin.

  • Colloid is a mixture of thyroglobulin and iodine and serves as a precursor of thyroid hormones (T3 & T4).

  • Parafollicular cells produce calcitonin.

Thyroid Hormones

• Thyroid Hormones:

  • T3 (Triiodothyronine): Contains 2 tyrosines and 3 iodine atoms.

  • T4 (Thyroxine): Contains 2 tyrosines and 4 iodine atoms.

• Hormone Therapy: Levothyroxine is a synthetic form used for patients with low thyroid hormone production or post-thyroid gland removal.

Synthesis of Thyroid Hormones

• Process:

  1. Thyroglobulin synthesis and discharge into the follicle lumen.

  2. Iodide uptake and oxidation to iodine.

  3. Attachment of iodine to thyroglobulin tails (20 tyrosine amino acids).

  4. Endocytosis of colloid containing thyroglobulin.

  5. Lysosomal enzymes cleave T3 and T4, which diffuse into the bloodstream.

Transport and Regulation of T3 & T4

• Blood Transport:

  • ~70% bound to thyroxine-binding globulins (TBGs) and ~15% to albumin.

• Activity: T3 is 10 times more active than T4.

• Regulation: Negative feedback on Thyrotropin Releasing Hormone (hypothalamus) and Thyroid Stimulating Hormone (anterior pituitary).

• Goiter Causes:

  1. Overstimulation due to low iodine leading to lack of functional thyroid hormones.

  2. Overstimulation caused by antibody activity in Graves' disease.

Functions of Thyroid Hormones

• Metabolic Role:

  • Increases metabolic rate and heat production.

  • Promotes blood glucose and fat metabolism.

• Others:

  • Essential for growth and development of skeletal, nervous, and reproductive systems.

  • Helps maintain blood pressure through increased heart rate.

Iodine Deficiency (Hypothyroidism)

• Impact:

  • Affects approximately 2 billion people worldwide, leading to intellectual disability, especially in developing regions.

  • Severe cases can result in cretinism (stunted growth).

• Sources of Iodine: Seaweed, scallops, cranberries, milk, and eggs.

Hyperthyroidism (Graves Disease)

• Cause: Antibody activates the TSH receptor leading to overstimulation.

• Symptoms:

  • Increased metabolic rate resulting in weight loss and increased appetite.

  • Heat intolerance and increased sweating, elevated heart rate, nervousness, irritability, and muscle contractions.

Calcitonin

• Produced By: Parafollicular cells (C cells).

• Function: Reduces blood calcium levels by inhibiting osteoclast activity and stimulating calcium uptake into bone matrix.

• Therapeutic Use: Can be used in treating osteoporosis.

Pancreas Location and Functions

• Location: Posterior to the stomach and inferior to the liver.

• Functions: Exocrine (digestive enzymes) and endocrine (insulin and glucagon secretion).

Pancreatic Cells Type

• Types of Cells:

  • Alpha (α) cells: Produce glucagon.

  • Beta (β) cells: Produce insulin.

  • Both types regulated by blood glucose levels.

Glucagon Function

• Target: Majorly affects the liver.

• Release Triggers: Low blood glucose levels.

• Actions:

  • Increases blood glucose by promoting glycogenolysis and gluconeogenesis.

Insulin Function

• Target Cells: Liver, adipose, and muscles (skeletal and cardiac).

• Release Triggers: High blood glucose levels.

• Actions:

  • Lowers blood glucose by promoting glucose uptake and glycogen synthesis, converting glucose to fat, and inhibiting glycogenolysis and gluconeogenesis.

Regulation of Insulin Release

• Enhancing Factors:

  • Elevated blood glucose, amino acids, and fatty acids.

  • Acetylcholine release due to parasympathetic stimulation.

• Inhibiting Factors:

  • Epinephrine and norepinephrine release.

Insulin Release Mechanism

1. Glucose enters pancreatic β-cell via facilitated diffusion.

2. Converts glucose to pyruvate, stimulating ATP production.

3. Increased ATP/ADP ratio leads to closure of K+ ATP channels, causing cell membrane depolarization.

4. Influx of Ca2+ triggers exocytosis of insulin.

Homeostatic Imbalances of Insulin

• Hyperinsulinism: Excess insulin leading to:

  • Hypoglycemia (low blood glucose), potentially causing disorientation, unconsciousness, or death.

  • Reduced receptor sensitivity can lead to hyperglycemia, with fat usage causing ketone generation and increased diabetes risk.

Causes of Diabetes Mellitus

• Diabetes Mellitus (DM):

  • Caused by hyposecretion (Type 1 + Type 2) or hypoactivity (Type 2) of insulin.

• Symptoms: Hyperglycemia leads to glucose in urine (glycosuria), increased urine output (polyuria), excessive thirst (polydipsia), and hunger (polyphagia).

Prolonged Hyperglycemia Effects

• High blood glucose (>200 mg/dL) results in:

  • Glycosylation of proteins/lipids, damaging neurons and cardiovascular system.

  • Kidney damage and retinopathy, leading to vision loss.

  • Delayed wound healing, leading to severe complications like amputations.

Diabetes Mellitus: Type 1

• Description: Autoimmune disease affecting insulin-producing β-cells; requires lifelong insulin injections for survival.

• Prevalence: Occurs frequently at a young age.

Diabetes Mellitus: Type 2

• Description: Most common in older, overweight individuals.

  • Results from insulin receptor insensitivity or inadequate insulin production.

• Treatment: May not require insulin; use of medications such as Metformin and Sulfonylureas can help improve insulin sensitivity.

Gestational Diabetes

• Description: High blood glucose levels occurring during pregnancy.

  • Treated by dietary regulation, with potential development into Type 2 Diabetes.

• Risk: Can lead to larger newborns.