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Human Anatomy and Physiology II KAAP310-14S Lectures: Tue Thu 9:30-10:45 Kirkbride 004 Labs (HSC 228) 3 0: Mon 10:10-12:05 Kelly Sebzda 3 1: Thu 2:30-4:25 Kelly Sebzda 3 2: Mon 2:30-4:25 Tyler Kmiec 3 3: Mon 4:40-6:35 Bryce Muth Run: Tue 2:15 From CSB entrance

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slide1
Human Anatomy and Physiology II
  • KAAP310-14S
      • Lectures: Tue Thu 9:30-10:45 Kirkbride 004
      • Labs (HSC 228)
      • 30: Mon 10:10-12:05 KellySebzda
      • 31: Thu 2:30-4:25 Kelly Sebzda
      • 32: Mon 2:30-4:25 Tyler Kmiec
      • 33: Mon 4:40-6:35 Bryce Muth
      • Run: Tue 2:15 From CSB entrance
  • Course Web Site www.udel.edu/sakai
  • William Rose [email protected] Rust 148
  • Kelly [email protected] 201
  • Tyler [email protected] 201
  • Bryce [email protected] 201

Department of Kinesiology and Applied Physiology

slide2
Human Anatomy and Physiology II

KAAP310-14S

Grading – see syllabus.

75% Classroom

70%: Ten tests (worst is dropped so nine count)

5%: Clicker

25% Laboratory

Department of Kinesiology and Applied Physiology

slide3
Human Anatomy and Physiology II

KAAP310-14S

UD Capture: Recording of what is projected on screen and classroom audio. http://udcapture.udel.edu/2013f/kaap310-010/

Clickers: Register your clicker on Sakai.

Clicker questions: 1 point for answering, 1 more point if correct.

Clicker grade: Full credit if you get 75% or more of the points available. Reduced proportionally if not.

If a student is observed using more than one clicker, both clicker numbers will be noted and grades reduced for both students.

  • No adjustments for forgotten or broken clickers, low batteries, etc.

Department of Kinesiology and Applied Physiology

slide4
Human Anatomy and Physiology II

KAAP310-14S

  • Tips
  • This class is not the same as KAAP 309.
  • Do not rely on memorization.
  • Understanding physiology requires knowing more than the what or where. You need to understand the why and the how.
slide5
Human Anatomy and Physiology II

KAAP310-14S

  • Tips
  • Everyone will work hard.
  • Read the book, come to class, ask questions.
  • Use the recorded lectures to review and not as a substitute for coming to class.
  • Use the online resources.
exam questions
Exam Questions

Knowledge

Comprehension

Application

knowledge question
Knowledge Question

________ are chemical messengers that are released in one tissue and transported in the bloodstream to alter the activities of specific cells in other tissues.

Hormones

Neuropeptides

Neurotransmitters

Humoral antibodies

none of the above

comprehension question
Comprehension Question

An activated G protein can trigger

the opening of calcium ion channels in the membrane.

the release of calcium ions from intracellular stores.

a fall in cAMP levels.

a rise in cAMP levels.

all of the above

application question
Application Question

Destruction of the supraoptic nucleus of the hypothalamus would have which result?

loss of emotional response

loss of GH secretion

loss of ADH secretion

loss of loss of regulatory factor secretion

loss of melatonin secretion

endocrine system overview
Endocrine System: Overview
  • Controls and integrates
    • Reproduction
    • Growth and development
    • Maintenance of electrolyte, water, and nutrient balance of blood
    • Regulation of cellular metabolism and energy balance
    • Mobilization of body defenses
  • Acts with the nervous system to coordinate and integrate the activity of body cells
  • Influences metabolic activities by means of hormones transported in the blood
  • Responses occur more slowly but tend to last longer than those of the nervous system
  • Endocrinology
    • Study of hormones and endocrine organs
slide11
Other tissues and organs that produce hormones: adipose cells, thymus, cells in walls of the small intestine, stomach, kidneys, heart

Pineal gland

Hypothalamus

Pituitary gland

Thyroid gland

Parathyroid glands

(on dorsal aspect

of thyroid gland)

Thymus

Adrenal glands

Pancreas

Ovary (female)

Testis (male)

Figure 16.1

chemical messengers
Chemical Messengers
  • Hormones: long-distance chemical signals that travel in the blood or lymph
  • Autocrines: chemicals that exert effects on the same cells that secrete them
  • Paracrines: locally acting chemicals that affect cells other than those that secrete them
  • Autocrines and paracrines are local chemical messengers and will not be considered part of the endocrine system
mechanisms of hormone action
Mechanisms of Hormone Action
  • Hormone action on target cells may be to
    • Alter plasma membrane permeability of membrane potential by opening or closing ion channels
    • Stimulate synthesis of proteins or regulatory molecules
    • Activate or deactivate enzyme systems
    • Induce secretory activity
    • Stimulate mitosis
chemistry of hormones
Chemistry of Hormones
  • Two main classes

1. Amino acid-based hormones

      • Amino acid derivatives, peptides, and proteins

2. Steroids

      • Synthesized from cholesterol
      • Gonadal and adrenocortical hormones
1 water soluble hormones all amino acid based hormones except thyroid hormone
1. Water-soluble hormones (all amino acid–based hormones except thyroid hormone)
  • Two mechanisms, depending on their chemical nature
    • Water-soluble hormones (all amino acid–based hormones except thyroid hormone)
      • Cannot enter the target cells
      • Act on plasma membrane receptors
      • Coupled by G proteins to intracellular second messengers that mediate the target cell’s response

Extracellular fluid

Hormone (1st messenger)binds receptor.

G protein (GS)

Receptor

  • Cannot enter the target cells. Act on plasma membrane receptors. Coupled by G proteins to intracellular second messengers that mediate the target cell’s response

Cytoplasm

2 lipid soluble hormones steroid thyroid hormones
2. Lipid-soluble hormones (steroid/thyroid hormones)

Steroidhormone

Plasmamembrane

Extracellular fluid

The steroid hormonediffuses through the plasmamembrane and binds anintracellular receptor that directly activates genes.

Cytoplasm

Receptorprotein

Receptor-hormonecomplex

Nucleus

plasma membrane receptors and second messenger systems camp
Plasma Membrane Receptors and Second-Messenger Systems - cAMP

Extracellular fluid

1

Hormone (1st messenger)binds receptor.

Adenylate cyclase

G protein (GS)

5

cAMP acti-vates proteinkinases.

Receptor

Activeproteinkinase

GDP

Inactiveprotein kinase

2

3

4

Receptoractivates Gprotein (GS).

G proteinactivatesadenylatecyclase.

Adenylatecyclaseconverts ATPto cAMP (2ndmessenger).

Hormones thatact via cAMPmechanisms:

Triggers responses oftarget cell (activatesenzymes, stimulatescellular secretion,opens ion channel,etc.)

GlucagonPTHTSHCalcitonin

EpinephrineACTHFSHLH

Cytoplasm

Figure 16.2

plasma membrane receptors and second messenger systems
Plasma Membrane Receptors and Second-Messenger Systems
  • cAMP signaling mechanism
    • Activated kinases phosphorylate various proteins, activating some and inactivating others
    • cAMP is rapidly degraded by the enzyme phosphodiesterase
    • Intracellular enzymatic cascades have a huge amplification effect
plasma membrane receptors and second messenger systems1
Plasma Membrane Receptors and Second-Messenger Systems
  • PIP2-calcium signaling mechanism

PIP2 – phosphatidyl inositol bisphosphate

  • DAG activates protein kinases; IP3 triggers release of Ca2+
  • Ca2+ alters enzymes or channels or binds to the regulatory protein calmodulin

http://www.ruf.rice.edu/~rur/issue1_files/barron.html

other signaling mechanisms
Other Signaling Mechanisms
  • Cyclic guanosine monophosphate (cGMP) is second messenger for some hormones
  • Some work without second messengers
    • E.g., insulin receptor is tyrosine kinase enzyme that autophosphorylates upon insulin binding  docking for relay proteins that trigger cell responses
intracellular receptors and direct gene activation
Intracellular Receptors and Direct Gene Activation

Steroidhormone

Plasmamembrane

Extracellular fluid

1

The steroid hormonediffuses through the plasmamembrane and binds anintracellular receptor.

Cytoplasm

Receptorprotein

Receptor-hormonecomplex

2

The receptor-hormone complex entersthe nucleus.

Hormoneresponseelements

Nucleus

3

The receptor- hormonecomplex binds a hormoneresponse element (aspecific DNA sequence).

DNA

4

Binding initiatestranscription of thegene to mRNA.

mRNA

5

The mRNA directsprotein synthesis.

New protein

Figure 16.3, step 5

intracellular receptors and direct gene activation1
Intracellular Receptors and Direct Gene Activation

Steroidhormone

Plasmamembrane

Extracellular fluid

1

The steroid hormonediffuses through the plasmamembrane and binds anintracellular receptor.

  • Steroid hormones and thyroid hormone
    • Diffuse into their target cells and bind with intracellular receptors
    • Receptor-hormone complex enters the nucleus
    • Receptor-hormone complex binds to a specific region of DNA
    • This prompts DNA transcription to produce mRNA
    • The mRNA directs protein synthesis

Cytoplasm

Receptorprotein

Receptor-hormonecomplex

2

The receptor-hormone complex entersthe nucleus.

Hormoneresponseelements

Nucleus

3

The receptor- hormonecomplex binds a hormoneresponse element (aspecific DNA sequence).

DNA

4

Binding initiatestranscription of thegene to mRNA.

mRNA

5

The mRNA directsprotein synthesis.

New protein

  • Promote metabolic activities, or promote synthesis of structural proteins or proteins for export from cell

Figure 16.3

target cell specificity
Target Cell Specificity
  • Target cells must have specific receptors to which the hormone binds
    • ACTH receptors are only found on certain cells of the adrenal cortex
    • Thyroxin receptors are found on nearly all cells of the body
target cell activation
Target Cell Activation
  • Hormones influence the number of their receptors
    • Up-regulation—target cells form more receptors in response to the hormone
    • Down-regulation—target cells lose receptors in response to the hormone
  • Target cell activation depends on three factors
    • Blood levels of the hormone
    • Relative number of receptors on or in the target cell
    • Affinity of binding between receptor and hormone
hormones in the blood
Hormones in the Blood
  • Hormones are removed from the blood by
    • Degrading enzymes
    • Kidneys
    • Liver

Half-life—the time required for a hormone’s blood level to decrease by half

  • Hormones circulate in the blood either free or bound
    • Steroids and thyroid hormone are attached to plasma proteins
    • All others circulate without carriers
  • The concentration of a circulating hormone reflects:
    • Rate of release
    • Speed of inactivation and removal from the body
interaction of hormones at target cells
Interaction of Hormones at Target Cells
  • Multiple hormones may interact in several ways
  • Permissiveness: one hormone cannot exert its effects without another hormone being present
  • Synergism: more than one hormone produces the same effects on a target cell
  • Antagonism: one or more hormones opposes the action of another hormone
  • Permissiveness: one hormone cannot exert its effects without another hormone being present
  • Synergism: more than one hormone produces the same effects on a target cell
  • Antagonism: one or more hormones opposes the action of another hormone
control of hormone release
Control of Hormone Release
  • Blood levels of hormones
    • Are controlled by negative feedback systems
    • Vary only within a narrow desirable range
  • Hormones are synthesized and released in response to
  • Humoral stimuli
  • Neural stimuli
  • Hormonal stimuli
humoral stimuli
Humoral Stimuli
  • Changing blood levels of ions and nutrients directly stimulates secretion of hormones
  • Examples:
humoral stimuli1
Humoral Stimuli

(a) Humoral Stimulus

Capillary blood contains

low concentration of Ca2+,

which stimulates…

1

  • Declining blood Ca2+ concentration stimulates the parathyroid glands to secrete PTH (parathyroid hormone)
  • PTH causes Ca2+ concentrations to rise and the stimulus is removed

Capillary (low

Ca2+ in blood)

Thyroid gland

(posterior view)

Parathyroid

glands

Parathyroidglands

PTH

…secretion of

parathyroid hormone (PTH)

by parathyroid glands*

2

Figure 16.4a

neural stimuli
Neural Stimuli

(b) Neural Stimulus

Preganglionic sympathetic

fibers stimulate adrenal

medulla cells…

1

  • Nerve fibers stimulate hormone release
    • Sympathetic nervous system fibers stimulate the adrenal medulla to secrete catecholamines

CNS (spinal cord)

Preganglionic

sympathetic

fibers

Medulla of

adrenal

gland

Capillary

…to secrete catechola-

mines (epinephrine and

norepinephrine)

2

Figure 16.4b

hormonal stimuli
Hormonal Stimuli

(c) Hormonal Stimulus

The hypothalamus secretes

hormones that…

1

  • Hormones stimulate other endocrine organs to release their hormones
    • Hypothalamic hormones stimulate the release of most anterior pituitary hormones
    • Anterior pituitary hormones stimulate targets to secrete still more hormones
    • Hypothalamic-pituitary-target endocrine organ feedback loop: hormones from the final target organs inhibit the release of the anterior pituitary hormones

Hypothalamus

…stimulate

the anterior

pituitary gland

to secrete

hormones

that…

2

Pituitary

gland

Thyroid

gland

Adrenal

cortex

Gonad

(Testis)

…stimulate other endocrine

glands to secrete hormones

3

Figure 16.4c

nervous system modulation
Nervous System Modulation
  • The nervous system modifies the stimulation of endocrine glands and their negative feedback mechanisms
    • Example: under severe stress, the hypothalamus and the sympathetic nervous system are activated
      • As a result, body glucose levels rise
interaction with a membrane bound receptor will transduce the hormonal message via
Interaction with a membrane-bound receptor will transduce the hormonal message via __________.
  • depolarization
  • direct gene activation
  • a second messenger
  • endocytosis
receptors for steroid hormones are commonly located
Receptors for steroid hormones are commonly located _________.
  • inside the target cell
  • on the plasma membrane of the target cell
  • in the blood plasma
  • in the extracellular fluid
the pituitary gland and hypothalamus
The Pituitary Gland and Hypothalamus
  • The pituitary gland (hypophysis) has two major lobes
      • Posterior pituitary (lobe):
        • Pituicytes (glial-like supporting cells) and nerve fibers
      • Anterior pituitary (lobe) (adenohypophysis)
        • Glandular tissue
case study
Case Study

History of Present Illness:

Lucia Sanchez is a 24 year-old woman who presented to her physician with a chief complaint of urinary frequency (polyuria) and excessive thirst (polydipsia). Her polyuria began abruptly two weeks prior to her doctor's appointment. Prior to that time, Lucia voided approximately five times per day. She estimated that she was now voiding twenty times per day. Two days prior to her visit to the doctor's office she was advised to collect her urine in order to check its volume in a 24 hour period; her total urine volume measured 12 liters. Lucia also noticed an intense craving for ice water that began at about the same time as her polyuria. If she did not have access to water, she would become extremely thirsty and dizzy. She denied any change in her appetite. She also denied the use of any medications.

pituitary hypothalamic relationships
Pituitary-Hypothalamic Relationships
  • Posterior lobe
    • A downgrowth of hypothalamic neural tissue
    • Neural connection to the hypothalamus (hypothalamic-hypophyseal tract)
    • Nuclei of the hypothalamus synthesize the neurohormones oxytocin and antidiuretic hormone (ADH)
    • Neurohormones are transported to the posterior pituitary
slide38
Paraventricular nucleus

Hypothalamus

1

Hypothalamic neurons synthesize oxytocin or antidiuretic hormone (ADH).

Posterior lobe

of pituitary

Optic

chiasma

Supraoptic

nucleus

Infundibulum

(connecting stalk)

2

Oxytocin and ADH are transported down the axons of the hypothalamic- hypophyseal tract to the posterior pituitary.

Inferior

hypophyseal

artery

Hypothalamic-

hypophyseal

tract

Axon terminals

3

Oxytocin and ADH are stored in axon terminals in the posterior pituitary.

Posterior lobe

of pituitary

4

When hypothalamic neurons fire, action potentials arriving at the axon terminals cause oxytocin or ADH to be released into the blood.

Oxytocin

ADH

pituitary hypothalamic relationships1
Pituitary-Hypothalamic Relationships
  • Anterior Lobe:
    • Originates as an out-pocketing of the oral mucosa
    • Hypophyseal portal system
      • Primary capillary plexus
      • Hypophyseal portal veins
      • Secondary capillary plexus
  • Carries releasing and inhibiting hormones to the anterior pituitary to regulate hormone secretion
slide40
Hypothalamus

Hypothalamic

neurons synthesize

GHRH, GHIH, TRH,

CRH, GnRH, PIH.

Anterior lobe

of pituitary

Superior

hypophyseal

artery

1

When appropriately stimulated, hypothalamic neurons secrete releasing or inhibiting hormones into the primary capillary plexus.

2

Hypothalamic hormones travel through portal veins to the anterior pituitary where

they stimulate or inhibit

release of hormones made in the anterior pituitary.

Hypophyseal

portal system

• Primary capillary

plexus

A portal system is two capillary plexuses (beds) connected by veins.

3

In response to releasing hormones, the anterior pituitary secretes hormones into the secondary capillary plexus. This in turn empties into the general circulation.

• Hypophyseal

portal veins

• Secondary

capillary plexus

GH, TSH, ACTH,

FSH, LH, PRL

Anterior lobe

of pituitary

anterior pituitary hormones
Anterior Pituitary Hormones
  • Growth hormone (GH)
  • Thyroid-stimulating hormone (TSH) or thyrotropin
  • Adrenocorticotropic hormone (ACTH)
  • Follicle-stimulating hormone (FSH)
  • Luteinizing hormone (LH)
  • Prolactin (PRL)
  • All are proteins
  • All except GH activate cyclic AMP second-messenger systems at their targets
  • TSH, ACTH, FSH, and LH are all tropic hormones (regulate the secretory action of other endocrine glands)
growth hormone gh or somatotropin
Growth Hormone (GH or Somatotropin)

Hypothalamus

secretes growth

hormone—releasing

hormone (GHRH), and

somatostatin (GHIH)

Inhibits GHRH release

Stimulates GHIH

release

Feedback

Anterior

pituitary

Inhibits GH synthesis

and release

  • Stimulates most cells, but targets bone and skeletal muscle
  • Promotes protein synthesis and encourages use of fats for fuel
  • Most effects are mediated indirectly by insulin-like growth factors (IGFs)

Growth hormone

Direct actions

(metabolic,

anti-insulin)

Indirect actions

(growth-

promoting)

Liver and

other tissues

Produce

Insulin-like growth

factors (IGFs)

Effects

Effects

Carbohydrate

metabolism

Extraskeletal

Skeletal

Fat

Increases, stimulates

Reduces, inhibits

Increased protein

synthesis, and

cell growth and

proliferation

Increased cartilage

formation and

skeletal growth

Increased

fat breakdown

and release

Increased blood

glucose and other

anti-insulin effects

Initial stimulus

Physiological response

Result

Figure 16.6

growth hormone gh or somatotropin1
Growth Hormone (GH or Somatotropin)

Hypothalamus

secretes growth

hormone—releasing

hormone (GHRH), and

somatostatin (GHIH)

Inhibits GHRH release

Stimulates GHIH

release

Feedback

Anterior

pituitary

Inhibits GH synthesis

and release

  • GH release is regulated by
  • Growth hormone–releasing hormone (GHRH)
  • Growth hormone–inhibiting hormone (GHIH) (somatostatin)

Growth hormone

Direct actions

(metabolic,

anti-insulin)

Indirect actions

(growth-

promoting)

Liver and

other tissues

Produce

Insulin-like growth

factors (IGFs)

Effects

Effects

Carbohydrate

metabolism

Extraskeletal

Skeletal

Fat

Increases, stimulates

Reduces, inhibits

Increased protein

synthesis, and

cell growth and

proliferation

Increased cartilage

formation and

skeletal growth

Increased

fat breakdown

and release

Increased blood

glucose and other

anti-insulin effects

Initial stimulus

Physiological response

Result

Figure 16.6

homeostatic imbalances of growth hormone
Homeostatic Imbalances of Growth Hormone
  • Hypersecretion
    • In children results in gigantism
    • In adults results in acromegaly
  • Hyposecretion
    • In children results in pituitary dwarfism
thyroid stimulating hormone thyrotropin
Thyroid-Stimulating Hormone (Thyrotropin)

Hypothalamus

TRH

Regulation:

  • Stimulated by thyrotropin-releasing hormone (TRH)
  • Inhibited by rising blood levels of thyroid hormones that act on the pituitary and hypothalamus

Anterior pituitary

TSH

Thyroid gland

Thyroid

hormones

Stimulates

Target cells

Inhibits

Figure 16.7

thyroid stimulating hormone thyrotropin1
Thyroid-Stimulating Hormone (Thyrotropin)

Hypothalamus

TRH

  • Produced by thyrotrophs of the anterior pituitary
  • Stimulates the normal development and secretory activity of the thyroid

Anterior pituitary

TSH

Thyroid gland

Thyroid

hormones

Stimulates

Target cells

Inhibits

Figure 16.7

adrenocorticotropic hormone corticotropin
Adrenocorticotropic Hormone (Corticotropin)
  • Secreted by corticotrophs of the anterior pituitary
  • Stimulates the adrenal cortex to release corticosteroids
  • Regulation of ACTH release
    • Triggered by hypothalamic corticotropin-releasing hormone (CRH) in a daily rhythm
    • Internal and external factors such as fever, hypoglycemia, and stressors can alter the release of CRH
gonadotropins
Gonadotropins
  • Follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
  • Secreted by gonadotrophs of the anterior pituitary
  • FSH stimulates gamete (egg or sperm) production
  • LH promotes production of gonadal hormones
  • Absent from the blood in prepubertal boys and girls
  • Regulation of gonadotropin release
    • Triggered by the gonadotropin-releasing hormone (GnRH) during and after puberty
    • Suppressed by gonadal hormones (feedback)
prolactin prl
Prolactin (PRL)
  • Secreted by lactotrophs of the anterior pituitary
  • Stimulates milk production
  • Regulation of PRL release
    • Primarily controlled by prolactin-inhibiting hormone (PIH) (dopamine)
  • Blood levels rise toward the end of pregnancy
  • Suckling stimulates PRH release and promotes continued milk production
the posterior pituitary
The Posterior Pituitary
  • Contains axons of hypothalamic neurons
  • Stores antidiuretic hormone (ADH) and oxytocin
  • ADH and oxytocin are released in response to nerve impulses
  • Both use PIP-calcium second-messenger mechanism at their targets
oxytocin
Oxytocin
  • Stimulates uterine contractions during childbirth
  • Also triggers milk ejection (“letdown” reflex) in women producing milk
  • Acts as a neurotransmitter in brain
antidiuretic hormone adh
Antidiuretic Hormone (ADH)
  • Hypothalamic osmoreceptors respond to changes in the solute concentration of the blood
  • If solute concentration is high
    • Osmoreceptors depolarize and transmit impulses to hypothalamic neurons
    • ADH is synthesized and released, inhibiting urine formation
antidiuretic hormone adh1
Antidiuretic Hormone (ADH)
  • ADH works at the kidney to control water loss
  • If solute concentration is high (sensed by osmoreceptors in the hypothalamus)
    • A large amount of ADH is released, inhibiting water loss
  • If solute concentration is low
    • ADH is not released, allowing water loss
  • Alcohol inhibits ADH release and causes copious urine output
homeostatic imbalances of adh
Homeostatic Imbalances of ADH
  • ADH deficiency—diabetes insipidus; huge output of urine and intense thirst
  • ADH hypersecretion (after neurosurgery, trauma, or secreted by cancer cells)—syndrome of inappropriate ADH secretion (SIADH)
case study1
Case Study

History of Present Illness:

Lucia Sanchez is a 24 year-old woman who presented to her physician with a chief complaint of urinary frequency (polyuria) and excessive thirst (polydipsia). Her polyuria began abruptly two weeks prior to her doctor's appointment. Prior to that time, Lucia voided approximately five times per day. She estimated that she was now voiding twenty times per day. Two days prior to her visit to the doctor's office she was advised to collect her urine in order to check its volume in a 24 hour period; her total urine volume measured 12 liters. Lucia also noticed an intense craving for ice water that began at about the same time as her polyuria. If she did not have access to water, she would become extremely thirsty and dizzy. She denied any change in her appetite. She also denied the use of any medications.

case study3
Case Study

Lucia was hospitalized and underwent an oral dehydration test. She was denied any fluid intake, and doctors carefully analyzed her vital signs and urine output during this process. Because she had been advised to drink a lot of water before coming to the hospital, her initial supine and upright blood pressure were normal. The analysis showed that Lucia was urinating at a rate of approximately 500 cc's per hour; her urine specific gravity remained at 1.001 even though she became dehydrated to the point where she became orthostatic (her blood pressure dropped when she changed from the supine to the upright position).

case study4
Case Study

Diagnosis: Central diabetes insipidus

Lucia was given ADH which resulted in a marked decline in her urine output from 500 cc/hour to 70 cc/hour. Nurses administered IV fluids to correct her dehydration. Lucia was discharged and instructed to take desmopressin acetate, an oral form of ADH. This will mimic her physiologic levels of ADH, and help her kidneys retain water.

slide60
An overview of the relationships between hypothalamic and pituitary

hormones, and some effects of pituitary hormones on target tissues

Hypothalamus

Indirect Control through Release

of Regulatory Hormones

Direct Release

of Hormones

Sensory

stimulation

Osmoreceptor

stimulation

Growth

hormone-

releasing

hormone

(GH-RH)

Growth

hormone-

inhibiting

hormone

(GH-IH)

Thyrotropin-

releasing

hormone

(TRH)

Prolactin-

releasing

factor

(PRF)

Corticotropin-

releasing

hormone

(CRH)

Prolactin-

inhibiting

hormone

(PIH)

Gonadotropin-

releasing

hormone

(GnRH)

Regulatory hormones are released into

the hypophyseal portal system for delivery

to the anterior lobe of the

pituitary gland.

Adrenal cortex

Anterior lobe of

pituitary gland

Posterior lobe

of pituitary gland

ADH

ACTH

Adrenal

glands

GH

Kidneys

TSH

OXT

Liver

MSH

PRL

Thyroid

gland

Males: Smooth

muscle in ductus

deferens and

prostate gland

LH

FSH

Somatomedins

Females: Uterine

smooth muscle and

mammary glands

Glucocorticoids

(steroid

hormones)

Melanocytes (uncertain

significance in healthy

adults)

Ovaries

of female

Bone, muscle,

other tissues

Testes

of male

Mammary

glands

Thyroid

hormones

Inhibin

Testosterone

Estrogen

Progesterone

Inhibin

thyroid gland
Thyroid Gland
  • Consists of two lateral lobes connected by a median mass called the isthmus
  • Composed of follicles that produce the glycoprotein thyroglobulin
  • Colloid (thyroglobulin + iodine) fills the lumen of the follicles and is the precursor of thyroid hormone
  • Parafollicular cells produce the hormone calcitonin
thyroid hormone th
Thyroid Hormone (TH)
  • Major metabolic hormone
  • Increases metabolic rate and heat production (calorigenic effect)
  • Plays a role in
    • Regulation of tissue growth
    • Development of skeletal and nervous systems
    • Reproductive capabilities
  • Actually two related compounds
    • T4 (thyroxine); has 2 tyrosine molecules + 4 bound iodine atoms
    • T3 (triiodothyronine); has 2 tyrosines + 3 bound iodine atoms

Affects virtually every cell in body

slide64
Thyroid follicle cells

Colloid

1

Thyroglobulin is synthesized anddischarged into the follicle lumen.

Tyrosines (part of thyroglobulinmolecule)

Capillary

4

Iodine is attached to tyrosinein colloid, forming DIT and MIT.

Golgiapparatus

RoughER

Thyro-globulincolloid

Iodine

DIT (T2)

MIT (T1)

3

Iodideis oxidizedto iodine.

2

Iodide (I–) is trapped(actively transported in).

Iodide (I–)

T4

5

Iodinated tyrosines arelinked together to form T3and T4.

T3

Lysosome

T4

6

Thyroglobulin colloid isendocytosed and combinedwith a lysosome.

T3

7

Lysosomal enzymes cleaveT4 and T3 from thyroglobulincolloid and hormones diffuseinto bloodstream.

Colloid inlumen offollicle

T4

T3

To peripheral tissues

Figure 16.9, step 7

transport and regulation of th
Transport and Regulation of TH
  • T4 and T3 are transported by thyroxine-binding globulins (TBGs)
  • Both bind to target receptors, but T3 is ten times more active than T4
  • Peripheral tissues convert T4 to T3
regulation of th
Regulation of TH
  • Negative feedback regulation of TH release
    • Rising TH levels provide negative feedback inhibition on release of TSH
    • Hypothalamic thyrotropin-releasing hormone (TRH) can overcome the negative feedback during pregnancy or exposure to cold

Hypothalamus

TRH

Anterior pituitary

TSH

Thyroid gland

Thyroid

hormones

Stimulates

Target cells

Inhibits

Figure 16.7

homeostatic imbalances of th
Homeostatic Imbalances of TH
  • Hyposecretion in adults—myxedema; endemic goiter if due to lack of iodine
  • Hyposecretion in infants—cretinism
  • Hypersecretion—Graves’ disease
    • Autoimmune disease
    • Exophthalmos

Figure 16.10

calcitonin
Calcitonin
  • Produced by parafollicular (C) cells
  • No known physiological role in humans
  • Antagonist to parathyroid hormone (PTH)
  • At higher than normal levels
  • Inhibits osteoclast activity and release of Ca2+ from bone matrix
  • Stimulates Ca2+ uptake and incorporation into bone matrix
  • Regulated by a humoral negative feedback mechanism (Ca2+ concentration in the blood)
  • No important role in humans; removal of thyroid (and its C cells) does not affect Ca2+ homeostasis
parathyroid glands
Parathyroid Glands
  • Four to eight tiny glands embedded in the posterior aspect of the thyroid
  • Contain oxyphil cells (function unknown) and chief cells that secrete parathyroid hormone (PTH) or parathormone
  • PTH—most important hormone in Ca2+ homeostasis
parathyroid glands1
Parathyroid Glands

Usually four (up to eight) tiny glands embedded in the posterior aspect of the thyroid

Pharynx

(posterior

aspect)

Chief

cells

(secrete

parathyroid

hormone)

Thyroid

gland

Parathyroid

glands

Oxyphil

cells

Esophagus

Trachea

Capillary

(a)

(b)

Figure 16.11

slide72
Hypocalcemia

(low blood Ca2+)

PTH is most important hormone for calcium homeostasis

PTH release from

parathyroid gland

Increases blood calcium levels 3 ways

Activation of

vitamin D by kidney

Ca2+ reabsorption

in kidney tubule

Osteoclast activity

in bone causes Ca2+

and PO43- release

into blood

Ca2+ absorption

from food in small

intestine

Ca2+ in blood

Initial stimulus

Physiological response

Result

homeostatic imbalances of pth
Homeostatic Imbalances of PTH
  • Hyperparathyroidism due to tumor
    • Bones soften and deform
    • Elevated Ca2+ depresses the nervous system and contributes to formation of kidney stones
  • Hypoparathyroidism following gland trauma or removal
    • Results in tetany, respiratory paralysis, and death if untreated
adrenal suprarenal glands
Adrenal (Suprarenal) Glands

Capsule

  • Paired, pyramid-shaped organs atop the kidneys
  • Structurally and functionally, they are two glands in one
    • Adrenal medulla—nervous tissue; part of the sympathetic nervous system
    • Adrenal cortex—three layers of glandular tissue that synthesize and secrete corticosteroids

Zona

glomerulosa

Zona

fasciculata

Adrenal gland

Cortex

• Medulla

• Cortex

Zona

reticularis

Kidney

Adrenal

medulla

Medulla

(a) Drawing of the histology of the

adrenal cortex and a portion of

the adrenal medulla

adrenal cortex
Adrenal Cortex

Capsule

Zona

glomerulosa

mineralocorticoids

Zona

fasciculata

Adrenal gland

glucocorticoids

Cortex

• Medulla

• Cortex

Zona

reticularis

Kidney

sex hormones,

or glucocorticoids

Adrenal

medulla

Medulla

(a) Drawing of the histology of the

adrenal cortex and a portion of

the adrenal medulla

Figure 16.13a

mineralocorticoids
Mineralocorticoids
  • Regulate electrolytes (primarily Na+ and K+) in ECF
    • Importance of Na+: affects ECF volume, blood volume, blood pressure, levels of other ions
    • Importance of K+: sets RMP of cells
  • Aldosterone is the most potent mineralocorticoid
    • Stimulates Na+ reabsorption and water retention by the kidneys; elimination of K+
mechanisms of aldosterone secretion
Mechanisms of Aldosterone Secretion
  • Renin-angiotensin mechanism: decreased blood pressure stimulates kidneys to release renin, triggers formation of angiotensin II, a potent stimulator of aldosterone release
  • Plasma concentration of K+: Increased K+ directly influences the zona glomerulosa cells to release aldosterone
  • ACTH: causes small increases of aldosterone during stress
  • Atrial natriuretic peptide (ANP): inhibits renin and aldosterone secretion, to decrease blood pressure
slide78
Aldosteronism—hypersecretion due to adrenal tumors
    • Hypertension and edema due to excessive Na+
    • Excretion of K+ leading to abnormal function of neurons and muscle

Primary regulators

Other factors

Blood volume

and/or blood

pressure

K+in blood

Stress

Blood pressure

and/or blood

volume

Hypo-

thalamus

Heart

Kidney

CRH

Direct

stimulating

effect

Anterior

pituitary

Renin

Initiates

cascade

that

produces

Atrial natriuretic

peptide (ANP)

ACTH

Angiotensin II

Inhibitory

effect

Zona glomerulosa

of adrenal cortex

Enhanced

secretion

of aldosterone

Targets

kidney tubules

Absorption of Na+ and

water; increased K+ excretion

The RAAS Song

Blood volume

and/or blood pressure

Figure 16.14

glucocorticoids cortisol
Glucocorticoids (Cortisol)
  • Cortisol(hydrocortisone) is the only significant glucocorticoid in humans
    • Released in response to ACTH, patterns of eating and activity, and stress
    • Prime metabolic effect is gluconeogenesis—formation of glucose from fats and proteins
    • Promotes rises in blood glucose, fatty acids, and amino acids – saves glucose for brain
  • Keep blood sugar levels relatively constant
  • Maintain blood pressure by increasing the action of vasoconstrictors
homeostatic imbalances of glucocorticoids
Homeostatic Imbalances of Glucocorticoids
  • Hypersecretion—Cushing’s syndrome
    • Depresses cartilage and bone formation
    • Inhibits inflammation
    • Depresses the immune system
    • Promotes changes in cardiovascular, neural, and gastrointestinal function
  • Hyposecretion—Addison’s disease
    • Also involves deficits in mineralocorticoids
      • Decrease in glucose and Na+ levels
      • Weight loss, severe dehydration, and hypotension
gonadocorticoids sex hormones
Gonadocorticoids (Sex Hormones)
  • Most are androgens (male sex hormones) that are converted to testosterone in tissue cells or estrogens in females
  • May contribute to
    • The onset of puberty
    • The appearance of secondary sex characteristics
    • Sex drive
    • Estrogens in postmenopausal women
adrenal medulla
Adrenal Medulla
  • Chromaffin cells secrete epinephrine (80%) and norepinephrine (20%)
  • These hormones cause
    • Blood vessels to constrict
    • Increased HR
    • Blood glucose levels to rise
    • Blood to be diverted to the brain, heart, and skeletal muscle
  • Epinephrine stimulates metabolic activities, bronchial dilation, and blood flow to skeletal muscles and the heart
  • Norepinephrine influences peripheral vasoconstriction and blood pressure
adrenal medulla1
Adrenal Medulla
  • Hypersecretion
    • Hyperglycemia, increased metabolic rate, rapid heartbeat and palpitations, hypertension, intense nervousness, sweating
  • Hyposecretion
    • Not problematic
    • Adrenal catecholamines not essential to life
slide85
Short-term stress

More prolonged stress

Stress

Nerve impulses

Hypothalamus

CRH (corticotropin-

releasing hormone)

Spinal cord

Corticotroph cells

of anterior pituitary

Preganglionic

sympathetic

fibers

To target in blood

Adrenal cortex

(secretes steroid

hormones)

Adrenal medulla

(secretes amino acid-

based hormones)

ACTH

Catecholamines

(epinephrine and

norepinephrine)

Mineralocorticoids

Glucocorticoids

Short-term stress response

Long-term stress response

1. Increased heart rate

2. Increased blood pressure

3. Liver converts glycogen to glucose and releases

glucose to blood

4. Dilation of bronchioles

5. Changes in blood flow patterns leading to decreased

digestive system activity and reduced urine output

6. Increased metabolic rate

1. Retention of sodium

and water by kidneys

2. Increased blood volume

and blood pressure

1. Proteins and fats converted

to glucose or broken down

for energy

2. Increased blood glucose

3. Suppression of immune

system

Figure 16.16

is the adrenal hormone responsible for maintaining appropriate blood sodium levels
__________ is the adrenal hormone responsible for maintaining appropriate blood sodium levels.
  • Cortisol
  • DHEA
  • Aldosterone
  • Epinephrine
slide87
During times of stress, elevated levels of _______ often occur, which explains why we get a cold during final exam time.
  • cortisol
  • aldosterone
  • ACTH
  • androgens
pineal gland
Pineal Gland
  • Small gland hanging from the roof of the third ventricle
  • Pinealocytes secrete melatonin, derived from serotonin
  • Melatonin may affect
    • Timing of sexual maturation and puberty
    • Day/night cycles
    • Physiological processes that show rhythmic variations (body temperature, sleep, appetite)
pancreas
Pancreas
  • Triangular gland behind the stomach
  • Has both exocrine and endocrine cells
    • Acinar cells (exocrine) produce an enzyme-rich juice for digestion
    • Pancreatic islets (islets of Langerhans) contain endocrine cells
      • Alpha () cells produce glucagon (a hyperglycemic hormone)
      • Beta () cells produce insulin (a hypoglycemic hormone)
slide90
Pancreatic islet

•  (Glucagon-

producing)

cells

•  (Insulin-

producing)

cells

Pancreatic acinar

cells (exocrine)

glucagon and insulin
Glucagon and Insulin
  • Effects of Glucagon
  • Major target is the liver, where it promotes
    • Glycogenolysis—breakdown of glycogen to glucose
    • Gluconeogenesis—synthesis of glucose from lactic acid and noncarbohydrates
    • Release of glucose to the blood
  • Effects of insulin
    • Lowers blood glucose levels
    • Enhances membrane transport of glucose into fat and muscle cells
    • Inhibits glycogenolysis and gluconeogenesis
    • Participates in neuronal development and learning and memory
insulin action on cells
Insulin Action on Cells
  • Activates a tyrosine kinase enzyme receptor
  • Cascade leads to increased glucose uptake and enzymatic activities that
    • Catalyze the oxidation of glucose for ATP production
    • Polymerize glucose to form glycogen
    • Convert glucose to fat (particularly in adipose tissue)
slide93
Stimulates glucose uptake by cells

Tissue cells

Insulin

Stimulates

glycogen

formation

Pancreas

Glycogen

Glucose

Blood

glucose

falls to

normal

range.

Liver

Stimulus

Blood

glucose level

Stimulus

Blood

glucose level

Blood

glucose

rises to

normal

range.

Pancreas

Liver

Glycogen

Glucose

Stimulates

glycogen

breakdown

Glucagon

Figure 16.18

factors that influence insulin release
Factors That Influence Insulin Release
  • Elevated blood glucose levels – primary stimulus
  • Rising blood levels of amino acids and fatty acids
  • Release of acetylcholine by parasympathetic nerve fibers
  • Hormones glucagon, epinephrine, growth hormone, thyroxine, glucocorticoids
  • Somatostatin; sympathetic nervous system
homeostatic imbalances of insulin
Homeostatic Imbalances of Insulin
  • Diabetes mellitus (DM)
    • Due to hyposecretion or hypoactivity of insulin
    • Three cardinal signs of DM
      • Polyuria—huge urine output
      • Polydipsia—excessive thirst
      • Polyphagia—excessive hunger and food consumption
    • Fats used for cellular fuel  lipidemia; if severe  ketones (ketone bodies) from fatty acid metabolism  ketonuria and ketoacidosis
    • Untreated ketoacidosis  hyperpnea; disrupted heart activity and O2 transport; depression of nervous system  coma and death possible
  • Hyperinsulinism:
    • Excessive insulin secretion; results in hypoglycemia, disorientation, unconsciousness
slide97
When the pancreas releases insulin in direct response to blood glucose, this is an example of ________ stimulation.
  • humoral
  • neural
  • hormonal
  • negative feedback
ovaries and placenta
Ovaries and Placenta
  • Gonads produce steroid sex hormones
  • Ovaries produce estrogens and progesterone
  • Estrogen responsible for:
    • Maturation of female reproductive organs
    • Appearance of female secondary sexual characteristics
    • With progesterone causes breast development and cyclic changes in the uterine mucosa
  • The placenta secretes estrogens, progesterone, and human chorionic gonadotropin (hCG)
testes
Testes
  • Testes produce testosterone that
    • Initiates maturation of male reproductive organs
    • Causes appearance of male secondary sexual characteristics and sex drive
    • Is necessary for normal sperm production
    • Maintains reproductive organs in their functional state
other hormone producing structures
Other Hormone-Producing Structures
  • Heart
    • Atrial natriuretic peptide (ANP) reduces blood pressure, blood volume, and blood Na+ concentration
  • Gastrointestinal tract enteroendocrine cells
    • Gastrin stimulates release of HCl
    • Secretin stimulates liver and pancreas
    • Cholecystokinin stimulates pancreas, gallbladder, and hepatopancreatic sphincter
other hormone producing structures1
Other Hormone-Producing Structures
  • Kidneys
    • Erythropoietin signals production of red blood cells
    • Renin (an enzyme) initiates the renin-angiotensin mechanism
  • Skin
    • Cholecalciferol, the precursor

of vitamin D

  • Adipose tissue
    • Leptin is involved in appetite control, and stimulates increased energy expenditure
    • Adiponectin – enhances sensitivity to insulin
other hormone producing structures2
Other Hormone-Producing Structures
  • Skeleton (osteoblasts)
    • Osteocalcin prods pancreatic beta cells to divide and secrete more insulin, improving glucose handling and reducing body fat
  • Thymus
    • Thymulin, thymopoietins, and thymosins are involved in normal the development of the T lymphocytes in the immune response
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