MT3 Study Guide

Study questions and topics to emphasize from Swinburne lectures on Endocrinology, GI

and Energy Homeostasis, Fluid Homeostasis

Endocrinology (lectures 24 & 25)

 What are the three structural classes of hormones, their precursors, common
features of their synthesis, & solubility? What are differences between these
classes of hormones
- Biogenic amines- derived from tyrosine
o Catecholamines: water-soluble, released via vesicles
o Thyroid hormones: lipid-soluble, made in thyroid gland involving
colloid particle, can diffuse through PM
- Peptide hormones-derived from preprohormones, prohormones
o Made in rough ER, packaged into vesicles
o Water-soluble
- Steroid hormones-derived from cholesterol
o Lipid soluble, levels are controlled at biosynthesis
o Bind to carrier proteins in blood
 What are similarities and differences in how hormones in the different structural
classes are released, transported in the bloodstream, and act on their target cells
 What contributes to the lifetime of a hormone?
- Hormone degradation in the liver, excretion in the kidneys, metabolism by cells,
endocytosis by target cells
 What can regulate hormone production?
- Ions, nutrients
- Other hormones
- neurotransmitters
 What are similarities and differences in how hormones can act on target cells?
- All hormones bind to specific receptors on target cells
- Hydrophilic hormones bind to receptors on the PM, usually GPCR or RTK,
activate downstream cascade
- Lipophilic hormones bind to receptors on the nucleus, alter gene transcription
directly by binding to DNA
 Where are hormone receptors located?
-either the plasma membrane or on the nucleus
 How can a hormonal response be fast?
- Hormones binding to PM receptors are fast
 What can make a hormonal response take longer?
- Hormones binding to receptors in the nucleus take longer
 How can hormones be involved in paraneoplastic syndrome?
- In paraneoplastic syndrome, tumors on organs can start to produce hormones
that the organ doesn’t usually produce
o Ex. lung cancer tumors secrete AVP and ACTH
 How can a plasma carrier protein influence the behavior of a hormone?
- Plasma carrier proteins can prolong the half life of the hormone
 What are the organizational principles of the hypothalamus and pituitary gland?
- Hypothalamus produces a hormone that is sent through the hypophyseal portal
 system to the pituitary gland, causing it to secrete another hormone.
 What is a portal system and how does it contribute to the function of
the hypothalamus and pituitary gland?
 What are differences between the anterior and posterior pituitary?
- Anterior pituitary: true endocrine gland, synthesizes own hormones
- Posterior pituitary: not true endocrine gland, releases vasopressin and oxytocin,
neural extension of hypothalamus
 What is the role of negative feedback in an HPX axis?
- Negative feedback from hormone produced by X organ helps to reduced
amounts of hormones produced by hypothalamus and pituitary
 How does negative feedback work in the Hypothalamic-Pituitary-thyroid axis?
- Thyroid releases T3 and T4, which then slow down production of TRH from the
hypothalamus and TSH from the pituitary
- Balance amount of T3 and T4 produced
 How do carrier proteins contribute to the Hypothalamic-Pituitary-thyroid hormone
axis?
- Since thyroid hormones are lipophilic, they cannot freely dissolve and travel
through the bloodstream.
- Carrier proteins help shuttle thyroid hormones through the blood.
 How do mutations in plasma carrier proteins influence the thyroid hormone
circuit?
 How does negative feedback work in the Hypothalamic-Pituitary-adrenal axis?
- Cortisol produced by adrenal glands slows production of ACTH from the pituitary
and CRH from the hypothalamus
 What are inputs to the hypothalamic-pituitary-adrenal axis?
 What does the hypothalamic-pituitary-adrenal axis promote?
 What are some pathologies caused by too much cortisol?
- Cushing syndrome- caused by ACTH-secreting pituitary adenomas, too much
cortisol produced
- Hypertension
- osteoporosis
 What are some useful applications of synthetic cortisol?
- Good for treating certain pathophysiological conditions
o Ex. eczema, arthritis

GI (lectures 28 & 29)

 What does the stomach do? Is it necessary? What does it help with?
-the stomach is involved in the breakdown of food into small macromolecules.
 What are key cells in the stomach? What do they secrete?
-chief cells- secrete pepsinogen
-parietal cells- secrete HCl
-mucus cells-secrete mucus
-D-cells- secrete somatostatin
-HCO3- cells-secrete HCO3-
-ECL cells-secrete histamine
 What is the mechanism of acid secretion by parietal cells?
- The K+/H+ pump helps to move H+ out of and K+ into the cell.
 - CO2 diffuses into parietal cell, broken down into HCO3- and H+ via carbonic
anhydrase
- HCO3- moves out of cell, causing Cl- to move into cell through antiporter
- As H- moves out of the cell, Cl- also moves out through channel, creating HCl
 For parietal cells, what would happen without carbonic anhydrase? Without ATP?
Without K+ leaks channels? What is the purpose of the 4 transporters and 1
enzyme?
- Without carbonic anhydrase, HCO3- cannot be formed, so Cl- cannot move
into the parietal cell
- Without ATP, H+ cannot move out of the cell since the K+/H+ pump will not
function
- Without K+ leak channels, the K+/H+ pump will not work, as K+ will build up in
the cell, removing its concentration gradient
 How are parietal cells regulated by gastrin, acetylcholine, histamine, and
somatostatin? How do antihistamines effect parietal cell activity? How are these
antihistamines different than the antihistamines used to treat acute allergic
responses?
- Gastrin- increases H+ release, HCl production
- Acetylcholine- increases H+ release
- Histamine-increases H+ release
- Somatostatin-decrease H+ release
- Antihistamines would decrease parietal cell activity
o These antihistamines bind to the H2 histamine receptor, which is
different from the receptor involved in allergies
 What are the tubulovesicular structures in parietal cells?
- These structures contain K+/H+ pump
 How was the physiology of parietal cells studied with isolated vesicles from
resting parietal cells?
- ATP: vesicles took up H+ in presence of ATP
- Valinomycin: served as K+ leak channels, promotes K+ uptake into
vesicles
 How does the stomach not digest itself?
- The stomach contains a lining of mucus and HCO3- that neutralizes stomach
acid and breaks apart pepsin
 How is pepsinogen activated?
- Pepsinogen is activated through its cleavage into pepsin by HCl. Pepsin helps to
activate more pepsinogen, resulting in more pepsin being made (positive
feedback)
 What is the cause of most peptic ulcers? Knowing this, how can we cure many
peptic ulcers?
- H. pylori bacteria causes most peptic ulcers.
- Antibiotics can treat peptic ulcers
 How is the tissue of the small intestine organized and how does this contribute
to its function?
 What does the exocrine pancreas secrete to help digestion in the small intestine?
- Duct cells secrete bicarbonate which helps to neutralize HCl coming from the
stomach
- Acinar cells secrete digestive enzymes involved in breakdown of sugars, nucleic
 acids, proteins, fats
 What does the liver make that helps digestion in the small intestine?
- Liver makes bile that helps to emulsify large fat blobs in the small intestine
 What does the gall bladder do?
- Stores extra bile produced by the liver
 What does the small intestine secrete to help with digestion and absorption?
- Mucus to lubricate chyme
- Salt water to lubricate chyme
- Enzymes to breakdown macromolecules
 Which cells and what processes use Na+/K+ ATPases? How would
their inhibition effect physiology? (be on the lookout for Na+/K+
ATPases)
 How are zymogens from the exocrine pancreas activated? Why not secrete
active proteases?
- Zymogens are activated via trypsin.
- Active proteases may affect the digestive organs by digesting them
when macromolecules are not present
 What do S-cells sense and what is their response?
- Sense increase in stomach acid, respond by releasing secretin, which causes
the release of HCO3- downstream to neutralize the acid
 What do I-cells sense and what is their response?
- Sense increases in fatty acid and amino acid intestinal levels, respond by
secreting CCK, which results in the secretion of digestive enzymes downstream
 What is the response to the hormone CCK for its different target cells and
tissues?
- CCK promotes secretions of digestive materials from target cells and
tissues
 What does CCK cause the gall bladder to do? What does CCK cause
the sphincter of Oddi to do?
- Causes gall bladder to contract, releasing bile into the small intestine
- Causes sphincter of Oddi to relax
 How do amphipathic bile salts help with digestion?
- Bile salts emulsify large fat droplets into smaller droplets
- Small droplets can be broken down into monoglycerides and fatty acids

 What is the hepatic portal system and how does it contribute to the function
of the GI system and nutrient absorption?
- Hepatic portal system collects nutrient-containing blood from GI tract
- Nutrients delivered to liver, where they are processed
- Liver removes unwanted materials, determines blood concentration of
nutrients
 How is fluid reabsorption coupled to glucose and ion transport?
- As glucose and ions are absorbed in the intestines, water molecules follow due
to osmosis.
 What is a healthy microbiome?
- Contains wide variety of microorganisms
- No harmful microorganisms
- Aids in digestion of materials, produces vitamins
Metabolism, Appetite, Thermogenesis (lectures 30, 31, & 32)

 What is the purpose of metabolism?

- Metabolism helps to manage energy for work
 What does the brain use for energy? Why?
- Glucose, it can cross the blood brain barrier
- Fatty acids can’t cross, so they’re not used
 What characterizes the fed metabolic state?
- State after a meal has been consumed
- Nutrients ingested and used for energy
 What characterizes the fasting metabolic state?
- Empty GI tract
- Energy supplied with body’s own storage (glucose, glycogen)
 How do beta cells sense plasma glucose levels?
- Glucokinase phosphorylates glucose and acts as a sensor of glucose level
o As glucose levels increase, activity of glucokinase increases
- Glucose enters cell through GLUT2 channel, undergoes cell respiration to
produce ATP
- High ATP/ADP levels causes K+ channels to close, causing depolarization in
beta cells, results in Ca2+ activating insulin secretion
 Understand the differences between glucokinase and hexokinase activity
and expression patterns and how they contribute to beta cell function
- Glucokinase has less of an affinity for glucose than hexokinase
- Glucokinase is not saturated in the fed state while hexokinase is
- Hexokinase is always working
- Glucokinase works more in fed state
 What is the primary response of target cells to increased plasma glucose levels?
 What does glucagon promote?
- Promotes conversion of glycogen into glucose in liver cells
- Promotes gluconeogenesis in liver cells
 What are different ways to diagnose diabetes?
 What are similarities and differences between type I and type II diabetes?
- Both involve impaired insulin function
- Type I: insulin is absent or in very low levels
- Type II: body is resistant to insulin function
 How does the hypothalamus integrate information to assess whether food
intake needs to increase?
 How was the hypothalamus first implicated in controlling hunger and satiety?
 How did a mutant yellow mouse contribute to identification of a neural circuit
controlling hunger and satiety?
- Agouti lethal yellow mutant mice possessed a mutant Ay gene that
stimulated yellow pigment and blocked melanocortin receptors
- Melanocortin receptors were thought to limit appetite, so suppressing
them would cause obesity
 What is channelrhodopsin and how does optogenetics help in the study of
neural circuits?
- Channelrhodopsin is a receptor in green algae that reacts in the presence of
light.
- Expressing channelrhodopsin in specific neurons can show what physiological
 function they are connected to
o Shine light onto neuron, subject has specific response
 Which neurons positively regulate a satiety circuit?
- AgRP neurons, produces AgRP which promotes food intake and decreases
metabolism
 Which neurons negatively regulate a satiety circuit?
- POMC neurons
- Mutations in POMC linked to obesity
 How do these circuits respond to leptin?
- AGRP neurons are inhibited
- POMC neurons are activated
 How did parabiosis experiments help characterize the roles of the proteins
encoded by Ob and Db
 What is leptin? What produces leptin and which cells respond to leptin?
- Leptin is a feedback signal that negatively regulates appetite
- Produced by adipose cells
- Binds to leptin receptors in arcuate neurons in brain
 Where is ghrelin produced and what suggests that it may be a hunger promoting
hormone?
- Produced in the stomach
 What are the benefits of being warm-blooded?
 What processes contribute to heat production and heat loss?
- Heat production: facultative thermogenesis (ex. shivering), obligatory
thermogenesis
- Heat loss: cutaneous vasodilation, sweating, behavioral modulation (ex. moving
from sun to shade)
 How does UCP1 activity lead to heat generation?
- UCP1 in brown adipocytes converts the potential energy generated by the H+
gradient in the mitochondria during oxidative phosphorylation into heat,
uncoupling ATP synthesis.
- UCP1 helps H+ bypass ATP synthase as it flows back into the matrix
 What signals regulate UCP1 activity and how?
- Cytosolic ATP/ADP regulate UCP1 activity
- When the body is warm, ATP/ADP inhibit UCP1
- When body is cold, inhibition of ATP/ADP is overcome by the presence of fatty
acids
 What variables modulate thermogenesis? And how?
- Sympathetic neural circuits- hypothalamus integrates info about body
temperature, instructs peripheral tissues to increase/decrease heat loss
- Endocrine inputs- cold stress activates TSH and epinephrine
o E/T3 work together to activate UCP1 in brown fat cells

Fluid homeostasis (lectures 33, 34, & 35)

 What are the major functions of the kidney?

- Maintain fluid and electrolyte balance
- Regulate blood pH
- Excretion of urea and other waste
 - Gluconeogenesis in fasting state
- Hormone production
 How is the kidney organized?
- Organized into nephron functional units
- Renal cortex: outside
- Renal medulla: inside
 Know the functional organization of the nephron
- Glomerular capsule-involve in cleaning blood
o Glomerulus-where filtration occurs
o Podocytes-slits in glomerulus
o Renal artery- brings blood to be filtered
 Afferent arteriole: brings blood to capsule
 Efferent arteriole: filtered blood leaves through here
- Proximal tubule
- Loop of henle
- Distal tubule
- Collecting duct
 What is the difference between a cortical nephron and a juxtamedullary nephron?
- Cortical: mediate movement of H2O and solutes
o No/short loops of Henle
- Juxtamedullary: generate osmotic gradient that powers H2O movement
between circulation and nephron
o Long loops of Henle, extends into inner medulla
 How is the nephron’s portal system organized?
 In what direction is fluid or solute moving during glomerular filtration?
Tubular reabsorption? Tubular secretion?
- Solute moves from the blood to the glomerular space during glomerular
filtration
- Tubular Reabsorption: fluid flows from the tubule back to the interstitial
fluid
- Tubular secretion: fluid flows from the interstitial fluid to the tubule
 What determines the excretion rate of something in the plasma?
 What is the diagnostic utility of inulin or creatinine?
- Since creatinine and inulin are mostly excreted in filtration, they can be used to
indicate changes in glomerular filtration rate
- Drop in GFR indicated by increased creatinine or inulin levels in the blood
 What is the structural organization that filters material as it moves from
the plasma into the renal tubule?
- Renal corpuscle
 What determines whether something passes from the plasma into the
renal tubule?
- Large size and negative charge prevents passage from plasma into renal
tubule
 The balance of which forces determine the glomerular filtration pressure
and rate? How might the pressure or filtration rate change in response to
perturbations?
- Balance of glomerular capillary blood pressure (PGC), fluid pressure on
bowmans space (PBS), and osmotic force from plasma proteins (piGC)
- GFP=PGC-PBS-piGC
 - Perturbations usually decrease pressure and filtration rate
 How would constriction or dilation of either the afferent or efferent
arterioles change the glomerular filtration rate?
- Constriction of afferent arterioles causes less blood to flow into
glomerulus, decreasing BP, therefore decreasing filtration rate
- Dilation of efferent arterioles also decreases BP, decreasing filtration
rate
 What processes prevents all filtered plasma from being exceted as urine?
 What is the role of Na+K+ ATPase activity in reabsorption?
- NaK pump helps to keep Na+ concentration low in the proximal tubule cells
- So, Na+ can flow from the tubule lumen into the tubule cells along its
concentration gradient
- NaK pump helps bring Na+ from tubule cells to interstitial fluid
 What prevents all the filtered glucose from being excreted?
- SGLT channels help reabsorb glucose
- Glucose travels along with Na+ along Na+ concentration gradient
 Why can the urine of patients with diabetes melitus taste sweet?
- Excess glucose in the blood as a result of diabetes saturates the SGLT
channels in the proximal tubule
- Not all glucose can be reabsorbed as a result, so some glucose is in the urine
 How are organic anions secreted? What is the role of Na+K+ ATPase in OA-
secretion?
- Secreted via indirect active transport
 What was a solution to extend the lifetime of penicillin in the blood?
- Using a competitive inhibitor with penicillin extended its lifetime in the blood
- Inhibitor blocked organic anion transporters, which usually filter out penicillin
 What is renal clearance rate? Why is it useful?
- Volume of plasma that can be completely cleared of a particular substance per
unit time
- CR=([substance in urine]*Vurine)/(time*[substance in plasma])
 What is the purpose of the loop of Henle? What is a countercurrent multiplier?
- Loop of henle helps to reabsorb water and NaCl from the filtrate
o Creates concentration gradient in kidney
- Countercurrent multiplier: as filtrate travels down descending loop, water
moves out, increasing concentration of filtrate
- At bottom of loop of henle, filtrate is very concentrated
- As filtrate moves up ascending loop, Na+ can move out of filtrate
 How does the organization of the vasa recta assist the loop of Henle?
- Vasa recta runs parallel to the loop of henle
- Helps to reinforce gradient made by loop of henle by preventing washout
of interstitial salts
 How does vasopressin regulate water reabsorption?
- Vasopressin increases water reabsorption
- Vasopressin initiates the adding of aquaporins to apical membrane of the
tubules of the nephron
 What is the integrated response to dehydration (low blood volume, low
blood pressure, and/or increased osmolarity)?
 Review the cardiovascular-nervous system response to reduced arterial
 pressure (lecture 20)
- Dehydrationdecrease in arterial pressuredecreased baroreceptor
firingincreased sympathetic outflow to heart, arterioles, veinsdecreased
parasympathetic stimulationincrease arterial pressure
 How does glomerular filtration rate contribute to the dehydration response?
- Reduced filtration rate causes reduced excretion rate, so less fluid is lost
 How does angiotensin contribute to the dehydration response?
- Angiotensin II promotes thirst and vasopressin release
- Also promotes vasoconstriction
 What regulates vasopressin release?
- Decrease in blood pressure and arterial stretch promote vasopressin release
- Osmoreceptors in OVLT and SFO sense changes in osmolality, activate
vasopressin neurons in hypothalamus
- Baroreceptors sense decrease in blood pressure, signal to vasopressin
neurons to release vasopressin
- Angiotensin II regulates vasopressin release too
 Why is thirst and appetite for water important for homeostasis?
- Helps us restore water lost from excretion
 What regulates thirst?
- Thirst controlled by OVLT and SFO of lamina terminalis of the brain
- OVLT: senses plasma osmolality
- SFO: senses osmolality and changes in blood volume by monitoring ANG II
levels
 What is experimental evidence that indicates that angiotensin regulates thirst
through the SFO?
- Lesions to the SFO reduced ANG II induced drinking of water
 What is experimental evidence that indicates that activation of a subset of
neurons in the SFO promotes thirst?
- CamKII/nNOS neurons were optogenetically activated in mice, which
caused them to drink water
 What is experimental evidence that indicates that a different subset of neurons in
the SFO inhibits thirst?
- Optogenetically activating different subset of neurons suppressed thirst in
mice