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123 Cards in this Set

  • Front
  • Back
Skeletal location of pituitary
Sella Turnica of the sphenoid bone
Symptom of pituitary growth
Loss of visual field and accuity as a result of compresion of the optic chiasm
Posterior Pituitary Origin
Neural process grows down from the diencephalon becoming the median eminence and neurohypophysis consisting mostly of hypothalamic neurons
Origin of anterior pituitary
Rahtke's Pouch grows up from roof of mouth forming the adenohypophysis
Hormones of the Anterior Pituitary
Prolactin (PRL)
Growth Hormone (GH)
Thyroid Stimulating Hormone (TSH)
Adrenocorticotropic Hormone (ACTH)
Follicle-Stimulating Hormone (FSH)
Luteinizing Hormone (LH)
Function of TSH
Stimulates secretion of Thyroid Hormone
Function of ACTH
Stimulates release of cortisol
ACTH Cell Type and target
Corticotroph
Adrenal Glands
TSH cell type and target
Thyrotroph
Thyroid Gland
GH cell type and target
Somatotroph
All Tissues
Vessels from hypothalamus to anterior pituitary
hypophyseal-portal circulation
Hypothalamic Hormone Stimulating ACTH
Corticotropin-Releasing Hormone (CRH)
Hypothalamic Hormone Stimulating TSH and PRL
Thyrotropin-Releasing Hormone (TRH)
Hypothalamic Hormone Stimulating GH
Growth Hormone-Releasing Hormone (GHRH)
Hypothalamic Hormone Inhibiting GH
Somatostatin
Release characterisitics of Hypothalamic Releasing Hormones
Secretion is in pulses to maintain Anterior Pituitary sensitivity. Constant stimulation downregulates Anterior Pituitary receptors
Function of GH
Direct Effect (Adult): Metabolic; Binds receptor on adipocytes stimulating lypolysis
Indirect Effect (Adolescence): Stimulates IGF-1 production in liver which causes cellular growth
Molecular action of GH
Binds GHR releasing associated JAK2 tyrosine kinase initiating phosphorylation cascade. Phosphorylation of STAT Transcription Factors causes gene transcription
Effects of GH on Chondrocytes
Increases Amino Acid uptake, Protein synthesis, DNA/RNA synthesis, Chondroitin Sulfate, Collagen, Cell Size and number= Linear Growth
Effects of GH on Metabolism
Increases Plasma Glucose and FFA's
Decreases Plasma Amino Acids and Urea
Effects of GH on Muscle
Increases Amino acid uptake and protein synthesis
Decreases Glucose uptake
= Increase Lean Body Mass
Effects of GH on Adipose
Decrease Glucose uptake
Increase Lypolysis
= Decrease Adipose cell size
Secretion of GH
10 Pulses per day
Nocturnal peak 1hr after stage 3/4
Highest levels during puberty
50% drop on levels every 7 years after puberty
Cause and Effect of Dwarfism
Pre-pubescent GH deficiency
Retarded Skeletal growth
Poor muscle development
Excessive subcutaneous fat
SX of adult GH deficiency
Lethargy
Central Obeisity
Increased CV disease
Decreased Bone Density
Cause & Effect of Gigantism
Pre-pubescent GH excess typically from pituitary tumors
Glucose intolerance/hyperinsulinism
CV hypertrophy
Cause & Effect of Acromegaly
Post-pubescent GH excess
Coursening of features from bone and connective tissue overgrowth
Think Skin
Decreased Subcutaneous fat
Glucose intolerance and diabetes
Thyroid functional anatomy
Follicular cells (Cuboidal Epithelial) arranged in a sphere arround a lumen, the Colloid, where Thyroid hormone is stored. TSH stimulates enlargement of follicular cells forcine thyroid hormone out of the Colloid
Three steps of Thyroid hormone synthesis
Iodide Metabolism
Tyrosine Iodination
Coupling of iodinated molecules with thyroglobulin (by TPO)
Hormones of the Thyroid
Thyroxine (T4)
Triiodothyronine (T3)
Iodide Metabolism
I- enters follicular cells by secondary active transport via electrochemical gradient and a 2NA-1I Symporter in the basal membrane (Called an iodide trap)
Tyrosine iodination
Tyrosine is glycosylated and exocytosed into the colloid
Iodide is carried into the colloid by pendrin.
Thyroid Peroxidase (TPO) Oxidizes and incorporated Iodide into tyrosine to produce either 3-Monoiodotyrosine (MIT) or 3,5-Diiodotyrosine (DIT)
Coupiling of Iodinated molecules
Thyroid Peroxidase (TPO) couples either two DIT or one MIT and one DIT to produce Thyoxine or Triiodothyronine respectively
Conversion of T4 to T3
Once released from the thyroid, 3,5,3',5'-tetraiodothyronine is activated in the periphery by either 5'-monodeiodinase to 3,5,3'-Triiodothyronine (T3) or 5-monodeiodinase to 3,3',5'-Triiodothyronine (Reverse T3/rT3)
What causes decrease in conversion of T4 to T3 and increase in T4 to rT3
Cortisol inhibits 5'-monodeiodinase shunting convertion of T4 from T3 to rT3. Fasting, Malnutrition, Physical Trauma (Burn injury). Deactivates T4 to an inactive form to slow metabolism, decrease temperature and enzyme activity, and conserve energy.
Binding proteins of T4/T3
T4/T3 are hydrophobic, require transport molecules
70% bound to Thyroxine-Binding Globulin (TBG)
29% bound to albumin
Very low levels of free hormone, but free hormone is active and responsible for effects and feedback
Regulation of Free/Bound T4 ratio
↓ in free T4 is reversed by dissociation of bound T4
Change in [TBG] is compensated for by ↑/↓ T4 release by thyroid
**Alterations in TBG do not disturb ratio if Thyroid gland is normal
Effect of Thyroid-Stimulating hormone (TSH)
Stimulates growth and vascularity of thyroid gland
Stimulates most steps in thyroid hormone synthesis
Iodide Uptake and oxidation
Iodination and coupling
Edocytosis of colloid
Thyroglobulin Proteolysis
Regulation of TSH
T4/T3 has a negative feedback effect on the Anterior pituitary
Repression of TSH gene
Suppression of TSH release
Down-regulation of TRH Receptors
What hormones does Somatostatin Inhibit
Anterior Pituitary:
Growht Hormone (GH)
Thyoid Stimulating Hormone (TSH)
Pancreas:
Insulin (SS from delta cells)
Glucagon
Where is Thyroxin Binding Globulin (TBG) synthesized?
Liver
What is the half-life of T4 and why is it so long?
6 Days
T4 has a much higher binding affinity for Thyroxin-binding hormone (TBG)
Why is T3 the biologically active hormone?
T3 has a much higher binding affinity for active receptors
When treating hypothyroidism, why is it better to give synthetic T4 than T3?
T4 is a better mimic of biological conditions (Biologically more T4 produced)
T4 has a longer Half-Life
MOA of T4/T3
T4/T3 enters the cell via carrier mediated transport →T4 is converted to T3 in the target cell → T3 binds to nuclear receptors causing DNA transcription and protein synthesis.
Physiological effects of T3 on target cells
Stimulates bone and CNS maturation
↑BMR
↑Mitochondiral # and size
↑O2 consumption
↑Na-K ATPase
↑Protein Synthesis and Degredation (Net Catabolic)
↑Heat Production
↑Metabolism
↑Glucose Absorbtion
↑Glycogenolysis
↑Gluconeogenesis
↑Lipolysis
↑Cardiac output
↑HR and SV
↑SBP and ↓DBP
Describe Sympathomimetic effect of Thyroid Hormones
Actions of T4/T3 resemble those if increased SNS activity
Reinforces CV respose to Epi/NE by ↑β-adrenergic receptor number, Coupling to Adenylate Cyclase, ↑cAMP
Cause & Effect of Creatinism
Adolescent Hypothyroidism
Impaired growth of cerebral and cerebellar cortex
Impaired proliferation of axons and dentrides
Impaired myelinization
S/SX of Adult Hypothyroidism
↓BMR → cold intolerance
Lethargy
Somnolence (Dowsiness)
Mental Slowness
Muscle Aches
Decreased Reflexes
Decreased Sweating
Weight Gain
Myedema (Mucopolysaccharide acculumation under eyes causing edema)
Goiter
Amenorrhea
Constipation
Causes of Hypothyroidism
Primary (Thyroid Failure)
Secondary (Pituitary/Hypothalamic Failure)
Iodide Insufficiency
What causes formation of a goiter?
Increases TSH or TSH like peptide (Thyroid Stimulating Immunoglobulins TSI)
Cause & Effect of Graves Disease
Hyperthyroidism
Exopthalamos (Forward displacement of eyes), Lid Retraction
Pretibital Myxedema (Hyaluronic Acid and Chondroitin Sulfate accululation in dermis)

↑BMR → Heat Intolerance
Restlessness
Palpatations
Muscle Weakness
Bruit over thyroid
Goiter
Causes of Hyperthyroidism
Primary Hyperthyroidism (Graves Disease)
Autoimmune disease involving TSH receptor, Thyroid Stimulating Immunoglobulins (TSI)
Secondary Hyperthyroidism
Excess TSH/TRH
Hypersecreting Thyroid Tumor
Lab tests for Thyroid function
Measure TOTAL T4/T3 and TSH levels in blood
What are the layers and associated hormone classes of the adrenal cortex
Zona Glomerulosa-Mineralocorticoids (Aldosterone)
Zona Fasciculata- Glucocorticoids (Cortisol)
Zona Reticularis- Androgens
What Hormones are produced in the Adrenal Medulla?
Catecholamines (Epi/NE)
What does ACTH effect?
Stimulates all steps in synthesis of Cortisol, Adrenal Androgens, and Aldosterone
** Only CORTISOL feeds back
Stimulates cell hyperplasia via IGF-1
Precursor of ACTH
Preproopiomelanocortin (POMC)
For what hormones is ACTH a precursor for?
Melanocyte-Stimulating Hormone (MSH)
Corticotropin-Like Intermediate Peptide (CLIP)
Describe secretion of Cortisol
Cortisol is secreted diurnaly and under stress
Secretion is pulsatile , amount of secretion does not vary, frequency of secretion pulse varies
What effect doe stress have on cortisol release?
Can override the negative feedback inhibition
Stress enhances CRH-ACTH release
What is the half-life of cortisol and how is it transported in the blood?
70 Minutes
Mostly transported by Corticosteroid-Binding Globulin (CBG), also by Abumin, 5% unbound
Cortisol MOA
Adrenal steroids diffuse into the cell → Receptor bound to Heat-Shock Proteins (HSP) is activated, HSP released → Activated receptor binds to and activated steroid response element → gene transcription and protein synthesis
Effects of Cortisol
(Most of Cortisols effects are Permissive, not initiate but enhances)
4 important functions:
Stimulates Gluconeogenesis in response to low blood glucose
Increases protein and lipid breakdown (For GNEO)
Anti-inflamatory effect
Immunosuppressive
Cortisol effect on metabolism
↑Blood Glucose (cost of protein and lipids)
Mobilizes protein and lipids
↑GNEO and responsiveness to glucagon and Epi
↓ Insulin dependant glucose uptake in muscle and adipose
↓Blocks Insulin-suppresion on hepatic glucose production
Permissive for lipolytic effects of catecholamines
↑Body Fat
↑appetite (CNS effect)
Stimulates lipogenesis in adipose of face and trunk causing accumulation in those areas
↑Protein breakdown by inhibiting AA utilization
=Cortisol is a catabolic, anti-anabolic, diabetogenic hormone
Stress induced Cortisol cumulative effect
Accentuates hyperglycemia and accelerates protein loss
Cortisol effect on Muscle
Basal levels are required for normal contractility
Excess levels cause muscle atrophy through protein wastage
Cortisol effect on Bone
Decreases bone formation
↓Vitamin D synthesis and blocks its action(Ca absorbtion from GI)
↑Urinary Ca excretion
↑Apoptosis of Osteoblasts and osteocytes
Stimulates osteoclasts increasing bone resorbtion
Actions of 1,25 Vitamin D
Increases dietary Calcium absorbtion
Increases dietary Potassium absorbtion
Increased bone reabsorbtion of calcium and phosphate
Cortisol effects on vasculature
Maintains normal BP
Permits responsivenes to angiotensin
↓Permeability of vasculature
(Can cause hypertension)
Cortisol effect on kidneys
↑GFR by ↓ preglomerular resistance and ↑ plasma flow
Feedsback and inhibits ADH (Vasopressin)
Cortisol effect on CNS
Acts on receptors in the hippocampus (Memory), reticular activating system (state of arousal), and Autonomic Nuclei of the Brainstem altering perceptual and emotional function
Cortisol effect on development
Facilitates in utero maturation of lungs, GI, CNS, Retina, and Skin
↑Surfactant Synthesis
Cortisol effect on immune system
Inhibits many steps in inflamation and immune system responses
Cause & Effect of Cushing's Syndrome
Hypersecretion of Cortisol
Redistribution of body fat, Central Obeisity and Moon face with thin extremities
Atrophy of skin and dermal connective tissue
Thinning of bone
Muscle wasting
Easy Bruising
Delayed Healing
Hypertension
Diabetes
Two types of Cushing's Syndrome
1. ACTH Dependent (Results in Adrenocortical Hyperplasia) (Most common)
a. Pituitary Microadenoma (Cushing's Disease)
b. ACTH Ectopic Tumor
c. CRH Ectopic Tumor
2.ACTH Independent (Results in Adrenocortical Atrophy)
a. Adrenal tumor
b. Iatrogenic (Induced by medical teatment)
Hypercortisolism Diagnostic Test
Dexamethasone Suppression test
Explain Dexamethasone Suppression Test
(Dexamethasone is a synthetic glucocorticoid with high affinity for cortisol receptor)
1. 1-md overnight suppression test (Screening)
Normal: Drop in Cortisol level
Abnormal: No drop in Cortisol

2. 8-mg overnight suppression test (Diagnostic)
Hypothalamic/Pituitary Hyperfunction-50% drop in Cortisol (ACTH Dependent)
Adrenal Hyperfunction **or Ectopic ACTH tumor- No drop in Cortisol (ACTH Independent)

3.Tesing ACTH level will differentiate b/w Adrenal tumor and Etopic ACTH Tumor.
High ACTH=Ectopic ACTH Tumor
Low ACTH Adrenal Tumor
Cause & Effect of Addison's Disease
Primary Adrenal Insufficiency- Autoimmune destruction of adrenal cortex leads to deficiency in cortisol, adrenal androgens, aldosterone, and high ACTH due to loss of Negative Feedback
Causes Hyperpigmentation, Weakness, Depression, Weighloss, Hypotension.
What causes hyperpigmentation in Addison's Disease?
Excess amounts of ACTH becomes degraded into Melanocyte-Stimulating Hormone (MSH) causing hyperpigmentation
Cause & Effect of Secondary Adrenal Insufficiency
Ususaly Iatrogenic and results in ACTH hyposecretion from receiving GCC medication excessively suppressing ACTH. Once off medication, there is a lack of ACTH available.
Causes same symptoms as Addison's Disease without Hyperpigmentation
Hypocortisolism Diagnostic Test
ACTH Stimulation Test
Describe ACTH Stimulation Test
Test evaluates Adrenal Cortex ability to respond to ACTH
1.Rapid ACTH Test (Screening)- Injection of Cosyntropin (ACTH Analogue)
Normal- Increase in Cortisol
Abnormal- No increase

2. Prolonged ACTH Test (Diagnostic)- IV injection of ACTH
Primary Adrenal Insufficiency-Low Cortisol (Gand is destroyed)
Secondary Adrenal Insufficiency- Moderate increase in Cortisol (Sluggish Response)
What causes Congenital Adrenal Hyperplasia?
An enzyme blockage that results in low Cortisol levels results in High ACTH causing Adrenal Hyperplasia
Anabolic hormones
Promote Synthesis and Store Energy
Insulin
Growth Hormone (GH)
Catabolic Hormones
Break down Fuel stores and release energy (ATP Production)
Cortisol
Glucagon
Catecholamines
Functions of the pancreas
Exocrine: Produces digestive enzymes
Endocrine: Produces Insulin (Beta-Cells), Glucagon (Alpha-Cells), and Somatostatin (Delta-Cells)
Describe morphology of insulin
Consists of 2 polypeptides, Alpha and Beta connected by 2 disulfide bridges.
Beta-chain contains core biological function (B24 + B25)
Alpha-chain contains speces-specific sites
Secretion of Insulin
Insulin is synthesized preproinsulin (Signal peptide+C-peptide+Insulin). Signal peptide and C-peptide are cleaved producing proinsulin ans insulin respectively.
Clearance of Insulin
The liver removes 50% of insulin in a single pass (Insulin half-life= 4-6 minutes). The liver does not remove C-Peptide- C+I released in 1:1 ratio, diagnostically useful
Insulin Receptors
Tyrosine Kinase Receptors
2A+2B subunits
Receptors can be downregulated (internalized)(Diabetes) or Upregulated (Exercise and Fasting)
Insulin physiologic effects
↓Lipolysis
↓Proteolysis
↓Gluconeogenesis
Biphasic Secretion of Insulin
Early Phase: Initial burst of insulin 10 minutes after a meal (Fusion of docked insulin granules) sensitizes receptors
(Absent in DMII)
Late Phase: Gradual increase in insulin (Mobilisation from pool)
Factors Stimulating Insulin Secretion
Metabolic Components
Glucose
Amino Acids
Fatty Acids
Ketones
Hormonal Componenets
Growth Hormone
Glucagon
Intesinal Nutrients
GI Hormones (Incretins: Glucagon-Like Peptide 1 (GLP-1)and Gastric Inhibitory Peptide (GIP))
What effect does Incretins have on Insulin release
Incretins (Glucagon-Like Peptide 1 (GLP-1)and Gastric Inhibitory Peptide (GIP)) are released by the GI increase insulin release before glucose rises in blood and enhances Insulin reaction to glucose
Factors Inhibiting Insulin Secretion
Insulin
Epinephrine
Serotonin
Major Tissues Insulin Acts on
Liver: Inhibits glucose production
Muscle: Promotes glucose uptake and protein synthesis
Adipose Tissue: Increases storage of fatty acids
Glucose Transporters and function
Glut1&3: Ubiquitous- Insulin Independent, Mediates basal glucose uptake, High glucose affinity
Glut2:Pancreatic B-cells+Hepatic Cells- Insulin Independent, Low affinity for glucose (Regulatory Capacity)
Glut4: SK Muscle, Heart, Adipose Tissue- Transporters are internally sequestered and require Insluin signal
Steps of Insulin secretion regulation
Glucose is transported into the cell vie Glut2 and converted to Pyruvate+ATP+NADPH
Increase in ATP and NADPH closes K+ Channel
Closing K+ causes depolarization and opening of voltage gated Ca++ channel
Increased Ca++ trigger exocytosis of Insulin granules
How do Sulfonylurea drugs increase insulin release
Sulfonylurea drugs close ATP-Sensitive K+ channels causing influx of Ca++ and exocytosis of Insulin granules
What is the effect of insulin on FFA conversion in the liver?
Insulin present: FFA's converted to VLDL and Triglycerides

Insulin absent: FFA's converted into Ketone acids. May result in Ketoacidosis (Only brain is capable of utilizing Ketone Acids for ATP production (During starvation))
Characteristics of Diabetes Millitus
Absolute or Reative deficiency of insulin/excess of Glucagon
Absolute-Lack of Insulin production
Relative- Insensitivity to Inslulin

Causes Hyperglycemia and 3 "Poly's"
Polyurea- Excess glucose acts as osmotic diuretic
Polydipsia- Dehydration from osmotic diuresis
Polyphagia- Resistance of Insulin receptors in hypothalamus regulating appetite + Low Intracellular Glucose
Diet which predisposes DMII
High Fat Diet, Not High Sugar Diet
Trans-fats increase risk
Polyunsaturated fats decrease risk by increasing membrane fluidity
Link between obeisity and Diabetes
Obeisity causes increase in Tumor Necrosis Factor-A (TNF-A) causing inflamation and alters insulin receptor
Risk factors for DMII
High trans-fat diet
High glycemic index foods (processed carbs and high fructose corn syrup)
Meat & Iron
Low Vitamin D (Vit. D reduces systemic inflamation)
Low activity
Smoking
Genetics (More so than DM1)
Insulin and glucose levels in developing diabetes
Insulin Resistance- Euglycemia + Hyperinsulinemia (Excess insulin produced to control glucose)

Impaired Glucose Tolerance- Hyperglycemia + Hyperinsulinemia (Cells increse resistance to high levels of insulin)

Diabetic- Hyperglycemic+Hypoinsulinemic (Insulin production is exhausted and blood glucose is unregulated)
Most common cause of insulin resistance
Post-receptor defect
Pathophysiology of Hyperglycemia
Tissues with Glut1 receptors allow high amounts of glucose into cells
This causes Advanced Glycation End Products- Glucose molecules binding to cellular proteins causing disfunction
High amounts of glucose in cells alters metabolism of glucose into deleterious forms.
Complications of hyperglycemia
Kidney Failure
Cardiovascular Disease
Retinopathy
Microvascular (Resulting in amputation)
What hormones are involved in the Counter-Regulatory response
Occurs during hypoglycemia <40mg/dl
GH, Epi, NE, Cortisol, and Glucagon all act on the liver to increase glucose production
Effects of Glucagon
Mobilization of Glucose in the liver
Increase Gluconeogenesis
Increase Glycolysis
Increases Ketogenesis in the liver
Directs FFA to B-oxidation to Ketone Acids
Glucagon synthesis
Synthesized as preproglucagon, converted to proglucagon, and glucagon

Increase synthesis
Low Glucose
Low FFA
Epi/NE
Inhibit Synthesis
High Glucose+FFA
Somatostatin
Insulin
PTH increases serum Ca++ in what ways
1. Activates osteoclasts to release Ca++ from bone (resorption)
2. Icreases reabsorption in distal tubules (kidneys)
3. Activation of Vitamin D to increase Ca absorption from the GI tract.
What is the function of PTH
Regulation of blood Ca++ and PO4- by:
Increasing bone resorbtion
Increase kidney resorbtion of Ca++
Increase PO4- secretion in kidney
Increase convertion of 25-hydroxycholecalciferol to 1,25-Dihydroxycholecalciferol
What is the function of Calcitonin
Calcitonin inhibits osteoclast activity and is stimulated by hypercalcemia
What can result from excess Vitamin D
Excess bone resorbtion and demineralization
Actions of 1,25-Dihydroxycholecalciferol
Increases transcription of Calcium binding protein, increasing intestinal absorbtion of Ca++ and PO4-
Increases reabsorbtion of Ca++ in distal tubules
Vitamin D Regulation
PTH regulates 1-alpha-hydroxylase, the enzyme responsible for converstion of 25-hydroxycholecalciferol to 1,25-Dihydroxycholecalciferol
(Occurs in the kidney)
↓ PTH, ↑ Ca, ↑ phosphate
Secondary Hypoparathyroidism due to excess Vitamin D
↑ PTH, ↓ Ca, ↓ phosphate
Secondary Hyperparathyroidism: Vitamine D deficiency
↓ PTH, ↓ Ca, ↑ phosphate
Primary Hypoparathyroidism: Surgical Removal of Parathyroid or Autoimmunity
↑ PTH, ↑ Ca, ↓ phosphate
Primary Hyperparathyroidism: Parathyroid Adenoma or Ectopic Parathyroid Secreting Tumor
Composition of Bone
Phosphate and Calcium precipitate forming Hydroxyapatite in the osteoid matrix