Patho Endocrine

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問題一覧

Endocrine system is a collection of glands that secrete ____.

hormones

Hormones are passed through the blood to a ____.

target organ

Target organs/tissues have cells with ____ that respond to the hormone.

receptors

Hormone/receptor interaction stimulates a _______ in the target cells.

chemical reaction

Cellular reactions _____ and _____ of the body.

control metabolism and maintain homeostasis

What distinguishes endocrine from exocrine glands?

Endocrine glands don’t have ducts

What endocrine glad cells create and secrete hormones?

glandular epithelium

Less often, some endocrine glands are made up of ___.

neurosecretory tissue

Modified neurons secreting chemical messengers (act as hormone instead of neurotransmitter) releasing them into the bloodstream

Neurosecretory cell

Can act as both hormone and neurotransmitter. When released by neurons, it diffuses across synapses binding to adrenergic receptors in postsynaptic neurons as a neurotransmitter. When it diffused into the blood, in the absence of postsynaptic cell, binding to postsynaptic receptors in distant target cells it is a hormone.

Norepinephrine

A gland that makes substances and releases them through a duct or opening to a body surface (sweat, lacrimal, salivary, mammary, digestive glands in the stomach, pancreas, and intestines).

Exocrine glands

Regulation of: growth and sexual maturation, cellular energy production utilization, glucose homeostasis, fluid and electrolyte balance, circulatory function.

Functions of the Endocrine System

Cross the cell membrane and interact with cellular genes. Steroid hormones made from cholesterol (soluble in fat not water). Made on-demand, persistent effect.

Lipid soluble hormones

An amine but lipid solube (T3 & T4)

Thyroxine

Cholesterol is precursor: estrogen, cortisol, aldosterone, progesterone, testosterone.

Steroids

Autocrine or paracrine action: leukotrines, prostacyclins, prostaglandins, thromboxanes

Derivatives of arachidonic acid

Interact with plasma membrane receptors and cause a cascade of events inside the cell. Protein/peptide hormones made from amino acids, soluble in water. Available in storage, transient effect.

Water soluble hormones

Growth hormones, insulin, leptin, prolactin

Peptides

Follicle-stimulating hormone; luteinizing hormones, thyroid-stimulation hormones (TSH)

Glycoproteins

Endorphins, calcitonin, glucagon, hypothalamic hormones, lipotropins

Polypeptides

Epinephrine and Norepinephrine

Amines

First messengers that usually don’t need second messenger, but sometime may bind to steroid hormone receptors and activate second messengers.

Lipid soluble hormones

Second messangers: cAMP, cGMP, IP3/DAG, Ca2+

Water soluble hormones

Number is up and down regulated by various stimuli

Receptors

Change membrane permeability, activate intracellular enzymes, activate genes

Intracellular signaling

Mediates the effect of the hormone on the target cell

Second messenger system

Steroid hormones result in DNA transcription and protein synthesis

Action causing protein synthesis

Hormone release is controlled by one or more of the following

1) chemical factors (glucose, Ca blood levels) 2) endocrine factors (hormone from one endocrine gland controlling another) 3) neutral control (stress-induced catecholamines from adrenal medulla)

Most common type of regulation, increased level of hormone inhibits further release.

Negative feedback

Surge of hormones, increased level of hormone stimulates further release. e.g. stress response (epi and cortisol)

Positive feedback

Periodic variation in hormone release

Cyclic variations

Located in the sella turcica, attached to the base of the brain by the pituitary stalk

Pituitary gland

Two lobes: Anterior and Posterior

Pituitary

Controls secretion of adrenal cortex hormones

Adrenocorticotropin (ACTH or corticotropin)

Controls secretion of thyroxine and triiodothyronine by thyroid gland

Thyroid Stimulating Hormone (TSH or thyrotropin)

Promotes mammary gland development and lactation

Prolactin (PRL)

Hypothalamus communicates with the anterior pituitary through the pituitary stalk via hormones and posterior pituitary through nerve impulses

Control of the pituitary by the hypothalamus

Regulates water excretion as urine by the kidneys

ADH/vasopressin

Facilities milk expression during breast feeding. Role in uterine contraction/labor initiation and progression.

Oxytocin

Growth of body tissues. Metabolic effect: fat and glucose utilization. Protein building. Bone and cartilage growth.

Growth Hormones

Helps body assemble and build new tissues -> increased mitosis, cell differentiation, cell hypertrophy.

GH effect on body tissues

Increased protein synthesis by cells. Increased mobilization of fatty acids from adipose (ketosis) -> increased serum fatty acid level and use of fatty acids for energy production. Decreased rate of glucose metabolism by cells and decreased glucose utilization (conserves carbohydrates) -> decreaed glucose uptake by skeletal muscle and increased insulin secretion and glucose production by liver.

Metabolic effects of GH

Enhances amino acid transport through membranes. Increases transcription of DNA. Enhances RNA translation and protein synthesis by ribosomes. Decreases catabolism of proteins and amino acids.

GH promotes protein building

Increases deposition of protein by chondrocytic and osteogenic cells. Increases rate of chondrocyte and osteocyte reproduction. Induces conversion of chondrocytes to osteocytes for new bone deposition (so cartilage can convert to bone). Most important role in children.

GH stimulates bone and cartilage growth

Iodines from dietary iodine are pumped from blood into _____

Thyroid gland

_____ regulates iodine pump activity based on concentrations of circulating thyroid hormone.

Thyroid stimulating hormone (TSH)

The ER synthesizes ______ protein

thyroglobulin

Formation of thyroxine (T4) and triiodothyronine (T3) is caused by ____ on the thyroglobulin

iodination of tyrosine

T4 and small amounts of T3 remain bound to _____ and are stored in ______.

thyroglobulin; gland follicles

Thyroid hormones are secreted from the follicles after cleavage from ___ by ____.

thyroglobulin; proteinases

____ regulates the release of the thyroid hormone.

TSH

TSH is released into the blood and binds to the _____ on the basolateral aspect of the thyroid follicular cell leading to activation of _____ and intracellular levels of ____ which activates _____ that phosphorlates different proteins to modify their functions.

thyroid-releasing hormone receptor (TSH-R); adenylyl cyclase; cAMP; protein kinase A (PKA)

Regulates protein, fat, carb metabolism, metabolic rate, body heat production. Maintains growth hormone secretion, skeletal muscle maturation, cardiac rate force and output, and GI tract secretion. Affects CNS development, respirations, and oxygen ultiization.

Physiologic functions of thyroid hormone

Most T4 is converted into ____

metabolically active T3

Thyroid hormone affects virtually ____. When it binds to its receptor it activates genes for ____ and _____, which causes increased oxygen and energy consumption.

every organ system; metabolic rate and thermogenesis.

Hypothalamus releases ____ into the hypothalamic-hypophyseal portal system to the ____. ____ stimulates ____ in the anterior pituitary go to release ____. ____ is a tropic hormone, which means it indirectly affects cells by stimulating other endocrine glands first. It binds to the TRH receptors on the ____, causing a signal cascade mediated by a G-coupled receptor leading to activation of _____, which hydrolyzes 4,5 PIP2 into inositol IP3 and 1,2-diacyclglycerol (DAG). These second messagers mobilize intracellular calcium stores and activate ____, leading to downstream gene activation and transcription of ____.

thyrotropin-releasing hormone (TRH); anterior pituitary gland; TRH; tryrotropin cells; thyroid-stimulating hormone (TSH); TRH; anterior pituitary gland; phosphoionositide-specific phospholipase C (PLC); protein kinase C; TSH

TRH also has a ____ on the pituitary gland through the hypothalamic-pituitary-prolactin axis and directly stimulates lactotropic cells in the anterior pituitary to produce ____, which causes breast tissue growth and lactation.

non-tropic effect; prolactin

Other substances like ___, _____, and ____ can stimulate the release of prolactin.

serotonin, gonadotropin-releasing hormone, and estrogen

Exocrine glands that secrete digestive juices

Acinar cells

Endocrine gland that secretes insulin, glucagon, somatostatin, and amylin

Islet of Langerhans

A peptide hormone that is co-secreted with insulin from the pancreatic Beta-cell that is deficient in diabetics, and inhibits glucagon secretion, delays gastric emptying, and acts as a satiety agent.

Amylin

AKA growth hormone-inhibiting hormone (GHIH), it produces neuroendocrine inhibitory effects across multiple systems. It is known to inhibit GI, endocrine, exocrine, pancreatic, and pituitary secretions, as well as modify neurotransmission and memory function in the CNS.

Somatostatin

36-amino acid peptide that has an important feedback inhibitor of pancreatic secretion after a meal.

Pancreatic polypeptide

Increased glucose uptake into cells (except neurons), increased cell membrane permeability to amino acids, K+, and Phos+. Protein, fat, and glucose synthesis. Storage of glucose as glycogen in liver and muscle. Growth and gene expression.

Insulin actions

Insulin target cells

Liver, Muscle, and Adipose Cells

Insulin decreases ____ in the liver and presents use of amino acids to form glucose

gluconeogenesis

Plasma insulin increases 10-20 fold within ___ minutes after eating.

3-5 mins

First insulin peak is ___ minutes after insulin is formed from ____ and ____.

5-10 mins; pre-insulin and pro-insulin

Second peak insulin is ____minutes as additional insulin is made

15 mins

Insulin plateau phase is ____.

2-3 hours

Reduction of serum glucose concentration turns off _____.

insulin synthesis and secretion

Excess serum amino acids promote protein synthesis. Gastrin, secretin, and gastric inhibitory peptide secretion cause anticipation of increased serum glucose levels. Growth hormone, cortisol, estrogen, and progesterone secretion. Parasympathetic nerve activation -controls digestion.

Other controls of insulin secretion

Opposes the effect of insulin by increasing serum glucose concentration. Stimulates glycogenolysis (formation of glucose by liver). Increases gluconeogenesis from amino acids. Activates adipose cell lipase to liberalize fatty acids for conversion to glucose. Increases myocardial contractility. Increases renal blood flow by dialting afferent arterioles. Enhances bile secretion. Inhibits gastric acid secretion.

Glucagon

Decreased serum glucose concentrations. Increased serum amino acid concentrations. Exercise.

Cause glucagon secretion

The shorter isoform works primarily in the brain, while the longer form operates in the GI tract with a 1/2 life of 1-3 mins.

Somatostatin

Acts locally in islet cells to decrease production of insulin and glucagon. Decreases stomach, duodenum, and gallbladder motility. Decreases secretion of digestive enzymes and absorption by the GI tract. Extends the period of time and emergy enter blood from digestion. Stimulated by increased serum glucose, fatty acids, and amino acids and the presence of GI hormones in response to food intake. Suppressed by GHIH from hypothalamus and suppresses GH too.

Somatostatin

Adrenal zona glomerulosa secretes ___ and causes _________.

aldosterone; salt regulation and water balance by affecting renal distal tubules

Adrenal zona fasciculata secretes _____ causing ______.

cortisol; anti inflammatory, decrease bone formation and muscle mass, increase blood glucose and glomerular filtration, and modulate emotions.

Adrenal zona reticularis secretes ____ and causes ______.

androgens; sexual maturation

Adrenal medulla secretes ____ causing _____.

epinephrine and norepinephrine; increased cardiac output and increases arterial blood pressure and peripheral vascular resistance, respectfully.

Mineralocorticoid that regulates electrolytes

Aldosterone

Glucocorticoid involved in carb, fat, and protein metabolism, stress response, inflammation and immune response, membrane stability, and intravascular volume and blood vessel tone.

Cortisol

Secretion of adrenocortical steroids is controlled by _____.

adrenocorticotropic hormone (ACTH)

Aldosterone secretion is controlled by ____.

angiotensin

Increases absorption of sodium and secretion of potassium. Increases intravascular fluid volume. Stimulates Na and K transport in sweat and salivary glands, and intestinal epithelial cells.

Functions of Aldosterone

Lipid soluble - diffuses through cell membrane. Binds with receptors in target cells. Aldosterone receptor complex enters cell nucleus. Gene transcription and protein synthesis provoked (makes Na and K exchange pump in kidneys)

Mechanism of Action for Aldosterone

Aldosterone insufficiency leads to ____.

Hyponatremia and Hyperkalemia

ACTH from anterior pituitary (primary method). Increased K in intravascular fluid. Decreased Na in intravascular fluid. Renin-angiotensin (primary stimulus).

Control of Aldosterone Secretion

Aldosterone causes kidneys to?

hold on to Na and water

Elevates serum glucose (gluconeogenesis and decreased glucose utilization by cells). Reduces protein stores (increases liver and plasma amino acids for glucose production). Promotes mobilization of fatty acids from adipose tissue increasing fatty acid levels and conserves carbs.

Metabolic Functions of Cortisol

Chronic, high cortisol levels over long period resulting in weight gain and fat deposition in face, chest, torso -> “moon face”. Most common cause = use of steroid drugs.

Cushing’s Syndrome

Usually caused my steroid use but can also occur from overproduction of cortisol by the adrenal glands.

Exogenous Cushing’s

Slow and difficult to diagnose, often caused by tumors of the adrenal glands or pituitary gland.

Endogenous Cushing’s

Has anti-inflammatory properties (stabilizes lysosomal membrane, decreases capillary membrane permeability, prevents migration of WBCs and phagocytosis of damaged cells, reduces IL-1 -> lowers fever, suppresses T-lymphocyte production, blocks allergic response)

Cortisol

Is lipid solube (diffuses through cell membrane) -> binds with receptors in target cells -> cortisol-receptor complex enters cell nucleus-> acts in specific regulatory DNA sequences -> induces/suppresses gene transcription and protein synthesis

Cortisol Mechanism of Action

Production of catecholamines is dependent on prescence of cortisol in adrenal cortex. Catecholamine receptor sensitivity is dependent on circulating cortisol. Cortisol can be up and down regulated by catecholamine receptors.

Cortisol in Catecholamine Function

ACTH secretion is controlled by ____ from the hypothalamus.

corticotropin-releasing hormone (CRH)

ACTH from the ____ stimulates ____ secretion.

anterior pituitary; cortisol

ACTH activate the _____ to synthesize steroids.

adrenal cortex

100

_____ is also produced cyclically as part of circadian rhythm.

Cortisol

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