Exam 2

Page 1: Understanding Extrinsic Control

Extrinsic Control Overview

• Extrinsic control regulates the activity of organs within the body through signaling from elsewhere.

• Hormones are utilized when organs require sustained action rather than speed.

Key Examples

• Two primary examples of extrinsic control are:

  • Endocrinology: Hormonal control of physiological processes.

  • Neurology: Nervous system signaling.

Definition of Hormones

• Hormones: Any chemical messenger secreted from ductless glands.

• They diffuse from interstitial space into the bloodstream.

Hormonal Signaling Pathways

• Endocrine Signaling: Uses hormones to send signals into the bloodstream.

• Neuroendocrine Signaling: Hormones are released from neurons into the blood.

• Paracrine, Autocrine, and Neurotransmitters: Do NOT use hormones; they act locally without entering the bloodstream.

Potency of Hormones

• Hormones are effective in very low concentrations.

Hypothalamic-Pituitary Axis (HP Axis)

• The hypothalamus receives input from the CNS and signals the pituitary gland to release hormones based on this input.

Five Main Axes

• Hypothalamic-Pituitary axes include:

  • Adrenal Axis

  • Thyroid Axis

  • Gonadal Axis

  • Liver Axis

  • Prolactin Axis

Exceptions to Hypothalamic Control

• Pancreas: Responds to humoral signals (e.g., glucose) to release insulin.

• Parathyroid: Responds to calcium levels to release parathyroid hormone; both are not controlled by the HP axis.

Endocrine Tissues

• Four primary tissues have exclusive endocrine functions:

  • Pituitary Gland

  • Thyroid Gland

  • Parathyroid Gland

  • Adrenal Gland

Types of Hormones

• Amines: Modified single amino acids.

  • Examples: Epinephrine (hydrophilic), Thyroid hormone (T3, T4; hydrophobic).

• Peptides: Chains of amino acids, regulated by gene expression.

  • Examples: CRH, ACTH, GH, oxytocin, vasopressin, insulin, PTH.

  • Stored in vesicles and released in pulses.

• Steroids: Non-polar and lipophilic hormones derived from cholesterol.

  • Examples: Estrogen, testosterone, cortisol, aldosterone.

POMC

• POMC (Proopiomelanocortin): Precursor peptide with regulatory roles.

Page 2: POMC and Cholesterol Metabolism

POMC Cleavage

• There are two propeptide convertases:

  • PC1: Cleaves POMC to create ACTH.

  • PC2: Produces a-MSH, B-MSH, and B-endorphin from POMC.

Hormonal Production from Cholesterol

• Cholesterol is produced from dietary LDL, hydrolysis of cholesterol esters, or de novo synthesis from acetyl CoA.

• ACTH, angiotensin II, and K channels mediate cholesterol release from the zona glomerulosa in the adrenal cortex.

Conversion of Cholesterol to Pregnenolone

• Cholesterol enters mitochondria (mediated by STaR) and is converted to pregnenolone by CYP11A1.

Subsequent Steps for Pregnenolone

• Pregnenolone diffuses to the smooth endoplasmic reticulum (sER).

• The specific hormone produced depends upon the enzymes present in that cell type.

Importance of Receptors

• Different receptors for the same hormone lead to varied physiological effects.

• Example: Epinephrine can cause vasodilation in one tissue and constriction in another.

Locations of Hormone Receptors

• Plasma Membrane: Primarily for peptide hormones (polar hormones).

• Intracellular: Specialized for steroids or non-polar amines.

• Nuclear: Receptors for non-polar hormones.

Effects of Lipophilic vs. Hydrophilic Hormone Receptors

• Lipophilic receptors activate gene transcription.

• Hydrophilic receptors activate secondary messenger systems.

Stimuli for Hormonal Release

• Neural Stimuli: Action potential increases hormone release.

• Hormonal Stimuli: One hormone triggers another's release.

Page 3: Feedback Mechanisms and Hormonal Pathways

Feedback Control Mechanisms

• Negative Feedback: A major homeostatic control mechanism where increased hormone levels inhibit further hormone release.

Feedback Loop Types

• Long Loop: Last hormone released provides feedback to the anterior pituitary or hypothalamus.

• Short Loop: Trophic hormone from the anterior pituitary inhibits the hypothalamus.

• Ultrashort Loop: The releasing hormone from the hypothalamus inhibits itself.

Pathways in the Hypothalamus

• Two pathways to the pituitary:

  • Neural Pathway: Neurons from the hypothalamus reaching the posterior pituitary (e.g., oxytocin and vasopressin).

  • Anterior Pathway: Uses releasing hormones that travel through a portal blood system to the anterior pituitary.

Steroid Hormones from the Adrenal Cortex

• Adrenocortical Hormones:

  • Glucocorticoids: Cortisol (primates, ungulates, carnivores) and corticosterone (birds, rodents).

  • Mineralocorticoids: Aldosterone.

  • Weak Androgens: Androstenedione, DHEA.

Cortisol Regulation

• Regulated by the HPA axis through CRH (Corticotropin-releasing hormone) and ACTH (Adrenocorticotropic hormone).

Primary Effects of Cortisol

• Increases blood glucose through gluconeogenesis in the liver.

Effects of Cortisol on Body Systems

• Cardiovascular: Maintains blood pressure.

• Immune Function: Anti-inflammatory.

• Bone: Decreases collagen synthesis and osteoblast activity.

• Muscle: Inhibits fibroblast and collagen production, leading to muscle atrophy.

Serum Cortisol Variability

• Serum cortisol reflects a circadian and pulsatile release pattern, peaking in the morning and during stress.

Page 4: Stress Response and Hormonal Disorders

Bodily Response to Stress

• Increased blood glucose, cardiac output, attention, and aggression while decreasing reproduction and digestion.

Long-Term Stress Adaptation

• Long-term stress can damage the negative feedback loop, leading to sustained hormone release.

Cushing’s Syndrome vs. Cushing’s Disease

• Cushing’s Syndrome: Due to primary adrenal hyperplasia with intact negative feedback, leading to excess cortisol release.

• Cushing’s Disease: Secondary excess ACTH from the pituitary, causing symptoms related to high ACTH.

Addison’s Disease

• A condition characterized by decreased synthesis of all adrenocortical hormones due to autoimmune destruction of tissue.

• Symptoms include stress-induced hypoglycemia and high ACTH levels.

Symptoms and Diagnostics for Addison’s Disease

• Anorexia, lethargy, weight loss, and limb lameness.

• Lab findings: decreased cortisol/aldosterone, hyponatremia/hyperkalemia.

• ACTH Stimulation Test: Exogenous ACTH administration to observe cortisol response.

Page 5: Anatomy of the Pituitary Gland

Pituitary Tissue Types

• Two main types formed from Rathke’s pouch:

  • Posterior Pituitary: Derived from the neuro ectoderm.

  • Anterior Pituitary: Derived from the adenohypophysis.

Origins of Neurons in Neural Pathway

• Magnocellular Neurons: Originate from the paraventricular and supraoptic nuclei, releasing oxytocin and vasopressin.

Vasopressin (VP) Release Mechanisms

• Stimulated by osmoreceptors detecting increased osmolarity, along with decreased blood volume signal.

Action of Vasopressin

• Increases fluid reabsorption in kidneys by binding to V2 receptors, activating cAMP pathways and inserting AQP2 channels into membranes.

Central vs. Nephrogenic Diabetes Insipidus

• Central Diabetes Insipidus: Result of head injury leading to VP deficiency.

• Nephrogenic Diabetes Insipidus: Defect in kidney response due to V2 receptor or G protein abnormalities.

Page 6: Diagnosing and Managing Diabetes Insipidus

Examination of a Case Study

• Dog presents with polyuria and polydipsia, low urine osmolality, high blood osmolality suggests diabetes insipidus.

• Water Deprivation Test: Tests the ability to concentrate urine under dehydration.

Differentiating Diabetes Insipidus Types

• VP Response Test: Assessment of kidney function in response to vasopressin; a significant increase indicates central diabetes; little change indicates nephrogenic.

SIADH Overview

• Syndrome of Inappropriate ADH (SIADH): Autonomous ADH release from tumor sources prevents negative feedback, leading to fluid retention.

Oxytocin and Social Bonding

• Oxytocin promotes social bonding, enhancing partnerships in species like prairie voles.

Positive Feedback Mechanism During Birth

• Oxytocin release leads to myometrial contractions to facilitate offspring delivery; initiated when receptor density increases.

Milk Let-Down Mechanism

• Positive feedback occurs through sensory inputs to stimulate milk release during breastfeeding.

Page 7: Cushing’s Disease and Its Symptoms

Presentation of Cushing's in Dogs

• Symptoms: PU/PD, dilute urine, panting, abdominal distension, thinning limb hair.

Typical Cushing's Presentation

• Abnormal fat deposition, skin thinning, muscle atrophy.

Acronym for Cushing's Symptoms

• CUSHING: Central obesity, urinary cortisol/glucose increase, suppressed immunity, hypercortisolism, iatrogenesis, neoplasms, glucose intolerance.

Blood Flow Through Adrenal Glands

• Blood flows from the suprarenal artery into the medullary arteriole before reaching other structures.

Zones of Hormone Release in Adrenal Gland

• Cortex:

  • Salt: Zona Glomerulosa (mineralocorticoids)

  • Sugar: Zona Fasciculata (glucocorticoids)

  • Sex: Zona Reticularis (androgens)

• Medulla: Releases catecholamines, mainly epinephrine.

Adrenal Gland Cellular Composition

• Three essential components:

  • Lipid droplets for cholesterol reserves

  • Mitochondria for energy production

  • Smooth ER for steroid synthesis.

Hormonal Control Overview

• Cholesterol to pregnenolone is regulated by ACTH levels.

Influence of Hormones on Steroid Production

• C-21 hydroxylase affects mineral hormone production, while C-17 hydroxylase influences glucocorticoids.

Page 8: Aldosterone Function and Regulation

Stimuli for Aldosterone Release

• Triggered by decreases in blood pressure, decreased extracellular fluid volume, or hyperkalemia.

Aldosterone's Mechanism of Action

• Binds to mineralocorticoid receptors in kidney tubule cells, regulating gene transcription for ion transport.

  • Sodium (Na+) reabsorption, potassium (K+) secretion lead to increased blood pressure.

Excess Aldosterone Condition

• Conn's Syndrome: Primary hyperaldosteronism resulting from adrenal tumors leading to hypertension, fatigue, and PU/PD.

Diagnosis of Excess Aldosterone

• Aldosterone:renin ratio can assist in diagnosis.

Steroid Transport in Blood

• Steroids are hydrophobic and require binding proteins for transport.

Blood Carrying Proteins for Cortisol and Aldosterone

• Cortisol: 75% transcortin, 15% albumin, 10% free.

• Aldosterone: 50% albumin, 10% transcortin, and 40% free.

Effects of Free Hormones

• Only free hormones are biologically active; there’s no storage of steroids.

Receptor Sharing Between Cortisol and Aldosterone

• Both receptors are ligand-inducible transcription factors, triggering similar actions but with distinct regulation mechanisms.

• 11B-HSD2 converts cortisol to inactive cortisone to prevent inappropriate activation of mineralocorticoid receptors.

Zona Reticularis Enzymatic Requirements

• Specific enzymes required for DHEA and androstenedione synthesis.

Sympathetic Fiber Origin

• Thoracolumbar region provides preganglionic fibers releasing acetylcholine, stimulating the adrenal medulla's chromaffin cells to release catecholamines.

Page 9: Catecholamines and Their Effects

Catecholamine Synthesis

• Precursor process: Tyrosine -> DOPA -> Dopamine -> Norepinephrine.

Additional Enzyme for Epinephrine Production

• PNMT: Needed for converting norepinephrine to epinephrine, influenced by cortisol concentration.

Catecholamines' Effects

• Rapid, short-lived response crucial for homeostasis in cardiac and vascular functions.

• Increased levels during hypotension, shock, heart failure, or hypoglycemia enhance cardiac contractility and increase heart rate/blood pressure.

Adrenergic Receptor Interactions

• Epinephrine has a higher affinity for B receptors affecting the heart and smooth muscle, while a receptors induce smooth muscle contraction.

Enzymes for Catecholamine Degradation

• MAO: Primarily acts on norepinephrine within the nervous system.

• COMT: Degrades norepinephrine and epinephrine in synaptic regions, liver, heart, kidneys.

VMA as a Diagnostic Marker

• Vanillylmandelic acid (VMA) serves as a urinary measure for sympathetic dysfunctions.

Disorders of the Adrenal Medulla

• Rare dysfunctions include hypo (e.g., adrenalectomy) and hyper (tumors secreting excess catecholamines).

Breeds Predisposed to Cushing’s Disease

• Common breeds: Poodles, Dachshunds, Boxers, Boston Terriers, and Yorkies.

Bloodwork Changes in Cushing’s

• Common findings: elevated ALT, hypercholesterolemia, hyperglycemia.

Cushing's in Cats

• Rare incidences, often related to concurrent diabetes mellitus.

Diagnostic Tests for Cushing’s

• Urine Cortisol:Creatinine Ratio: Often high.

• ACTH Stimulation Test: Evaluates adrenal response.

• Dexamethasone Challenge Test: Confirms Cushing’s disease versus syndrome based on expected feedback responses.