NVCC Bio 212

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Review slides Lecture Exam 3
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Overview of the Endocrine System
The endocrine system consists of - collections
of cells located in tissues scattered throughout
the body - that produce substances released into
the blood (hormones) - to ultimately affect the
activity and metabolism of target cells.
Secrete into Affect activity
Endocrine glands Blood Inside cells
Exocrine glands Ducts or on to free surface Outside cells
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Classification of Hormones
Amino acids
Amino Acid Derivatives
Peptides
Proteins, glycoproteins
Hormones
Steroids (cholesterol-derived)
Lipid Derived
Eicosanoids (cell membranes)(locally acting)
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Actions of Steroid Hormones

• hormone crosses membranes

• hormone combines with receptor in nucleus or
  cytoplasm

• synthesis of mRNA activated

• mRNA enters cytoplasm to direct synthesis of
  protein, e.g., aldosterone-gtNa/K Pump

(Thyroid hormone has a similar mechanism of
action, even though it is a tyrosine derivative)
Magnitude of cellular response proportional to
the number of hormone-receptor complexes formed
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Actions of Amino Acid-Derived Hormones

• hormone (first messenger) binds to receptor on
  cell membrane

• adenylate cyclase activated

• ATP converted to cAMP

• cAMP (second messenger) promotes a series of
  reactions leading to cellular changes

Magnitude of response is not directly
proportional to the number of hormone-receptor
complexes its amplified
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Control of Hormonal Secretions

• primarily controlled by negative feedback
  mechanism

3) Humoral
1) Hormonal
2) Neural
Control mechanisms for hormone release
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Target Cell Activation By Hormones

• Target cells must have specific receptors to be
  activated by hormones
• Magnitude of target cell activation depends upon
• Blood levels of the hormone
• Rate of release from producing organ
• Rate of degradation (target cells, kidney, liver)
• Half-life
• Relative numbers of receptors for the hormone
• Cellular receptors can be up- or down-regulated
• Affinity (strength) of binding of the hormone to
  its receptor

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Pituitary Gland Control

• Hypothalamic releasing hormones stimulate cells
  of anterior pituitary (adenohypophysis) to
  release their hormones
• Nerve impulses from hypothalamus stimulate nerve
  endings in the posterior pituitary
  (neurohypophysis) gland to release its hormones

Note the hypophyseal portal system of the
adenohypophysis (two capillaries in series)
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Hormones of the Anterior Pituitary (SeT GAP)
(an axis)
Tropic hormones control the activity of other
endocrine glands
All anterior pituitary hormones use second
messengers
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Overview of the Pituitary Hormones
Figure from Martini, Anatomy Physiology,
Prentice Hall, 2001
All anterior and posterior pituitary hormones
bind to membrane receptors and use 2nd messengers
(cAMP)
SeT GAP
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Hormone Summary Table I Pituitary Hormones
Tissue Tissue
Name Origin Destination Action on Target Tissue Control of Release1
FOLLICLE STIMULATING HORMONE (FSH) anterior pituitary males semiiferous tubules of testes females ovarian follicle males sperm production females follicle/ovum maturation Gonadotropin Releasing Hormone (GnRH)
LUETINIZING HORMONE (LH) anterior pituitary In males interstitial cells in testes in females mature ovarian follicle males testosterone secretion females ovulation Gonadotropin Releasing Hormone (GnRH)
THYROID STIMULATING HORMONE (TSH) anterior pituitary thyroid secrete hormones Thyrotropin Releasing Hormone (TRH)
GROWTH HORMONE (GH) anterior pituitary bone, muscle, fat growth of tissues Growth Hormone Rleasing Hormone (GHRH)
ADRENOCORTICO-TROPIC HORMONE (ACTH) anterior pituitary adrenal cortex secrete adrenal hormones Corticotropin Releasing Hormone (CRH)
PROLACTIN (PRL) anterior pituitary mammary glands produce milk Prolactin Releasing Hormone (PRH)
ANTI-DIURETIC HORMONE (ADH) (VASOPRESSIN) posterior pituitary distal convoluted tubule (DCT) reabsorption of water increases blood pressure increase in osmolarity of plasma or a decrease in blood volume
OXYTOCIN (OT) posterior pituitary uterine smooth muscle breast contraction during labor milk letdown Stretching of uterus infant suckling
Se(x)
T
G
A
P
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Hormone Summary Table II
Tissue Tissue
Name Origin Destination Action on Target Tissue Control of Release
TRIIODOTHYRONINE (T3) THYROXINE (T4) Thyroid (follicular cells) all cells increases rate of metabolism (BMR) Thyroid Stimulating Hormone (TSH)
CALCITONIN Thyroid (C cells) Intestine, bone, kidney Decreases plasma Ca2 (? intestinal absorp of Ca ? action of osteoclasts ? excretion of Ca by kidney ? plasma Ca2
PARATHYROID HORMONE (PTH) Parathyroids Intestine, bone, kidney Increases plasma Ca2 (? intestinal absorp of Ca ? action of osteoclasts ? excretion of Ca by kidney ? plasma Ca2
EPINEPHRINE/ NOREPINEPHRINE(Catecholamines) Adrenal Medulla cardiac muscle, arteriole and bronchiole smooth muscle, diaphragm, etc increases heart rate and blood pressure... (fight or flight) Sympathetic Nervous System
ALDOSTERONE (Mineralocorticoids) Adrenal Cortex Kidneys sweat glands salivary glands pancreas reabsorption of water and Na (increases blood pressure) and excretion of K (mineralocorticoid) Angiotensin II ? plasma Na ? plasma K
CORTISOL(Glucocorticoids) Adrenal Cortex all cells Diabetogenic anti-inflammatory(glucocorticoid) ACTH
INSULIN ß-cells of Pancreatic Islets all cells, liver and skeletal muscle pushes glucose into cells from blood, glycogen formation (decreases blood glucose) ? plasma glucose SNS
GLUCAGON a-cells of pancreatic Islets liver and skeletal muscle breakdown of glycogen (increase in blood glucose) ? plasma glucose
TESTOSTERONE Testes secondary sex organs development and maintenance LH
ESTROGEN Ovaries secondary sex organs development at puberty and maintenance throughout life LH
NATRIURETIC PEPTIDES atria and ventricles of heart adrenal cortex, kidneys increased excretion of sodium and water from kidneys, ? blood volume, ? blood pressure Stretching of atria and ventricles
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Renin-angiotensin Pathway
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Stress

• Types of Stress
• physical stress
• psychological (emotional) stress
• (Stress is any condition, physical or emotional,
  that threatens homeostasis)

• Stress Response (General Adaptation Syndrome
  GAS)
• hypothalamus triggers sympathetic impulses to
  various organs
• epinephrine is released
• cortisol is released to promote longer-term
  responses

• Three general phases of the GAS to stress ARE
• Alarm phase
• Resistance phase
• Exhaustion phase

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Responses to Stress
Exhaustion - ? lipid reserves - ? production of
glucocorticoids - electrolyte imbalance -
damage to vital organs
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Diabetes ( Overflow)

• Diabetes Mellitus (DM)
• Hyposecretion or hypoactivity of insulin
• Three Ps of Diabetes Mellitus (mellitum honey)
• Polyuria (increased urination)
• Polydipsia (increased thirst)
• Polyphagia (increased hunger)
• Hyperglycemia, ketonuria, glycosuria
• Renal Glycosuria
• excretion of glucose in the urine in detectable
  amounts
• normal blood glucose concentrations or absence of
  hyperglycemia
• Diabetes Insipidus (insipidus tasteless)
• Hyposecretion or hypoactivity of ADH
• Polyuria
• Polydipsia

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Functions of the Kidneys

• Make urine
• Regulate blood volume and blood pressure
• Regulate plasma concentrations of Na, K, Cl-,
  HCO3-, and other ions
• Help to stabilize blood pH
• Conserve valuable nutrients
• Assist the liver in detoxification and deamination

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Anatomical Features of Kidneys
Kidneys are retroperitoneal
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Location of Kidneys
Figure from Martini, Anatomy Physiology,
Prentice Hall, 2001
Located retroperitoneally from T12 to L3 Left
kidney is slightly higher than right
kidney Adrenal glands sit on the medial and
superior part of kidneys
Nephro(s) kidney Pyel(o) pelvis
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The Nephron
(80)
Vasa recta are associated with juxtamedullary
nephrons
(20)
Nephrons are the structural and functional units
of the kidney
Sympathetic nerve fibers from the ANS innervate
the kidney
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Blood Flow Through Kidney and Nephron
Know this!
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Renal Corpuscle (Glomerulus Capsule)
Efferent arteriole is smaller than the afferent
arteriole This creates a high pressure (55-60 mm
Hg) in the glomerular capillary bed
Podocytes form the visceral layer of the
glomerular capsule. Their pedicels (foot
processes) form filtration slits (or slit pores)
that function in forming filtrate.
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The Nephron
1. Glomerular capsule 2. PCT simple cuboidal
with a brush border 3. Thin segment of the
descending nephron loop - simple squamous
epithelium 4. Thick ascending nephron loop -
cuboidal/low columnar 5. DCT - simple cuboidal
with no microvilli (specialized for secretion,
not absorption)
(DCT)
(PCT)
The order of the parts of the nephron is
important to know
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Juxtaglomerular Apparatus
Juxtaglomerular cells (JG) - modified smooth
muscle cells in the wall of the afferent
arteriole that contract (and secrete renin) Cells
of the macula densa (MD) are osmoreceptors
responding to solute concentration of filtrate MD
JG cells juxtaglomerular apparatus
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Glomerular Filtrate and Urine Composition
(1.8 L/day)
Glomerular filtrate is about the same composition
as plasma H2O, glucose, amino acids, urea, uric
acid, creatine, creatinine, Na, Cl, K, HCO3-,
PO43-, SO42-. But notice how different the
composition of urine is. Additionally, note that
protein is not normally present in urine.
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Urine Formation
Fluid from plasma passes into the glomerular
capsule and becomes filtrate at an average rate
of 125 ml/minute. This is known as the
Glomerular Filtration Rate (GFR)

• Glomerular Filtration (GF) Adds to volume of
  urine produced
• substances move from blood to glomerular capsule

• Tubular Reabsorption (TR) Subtracts from volume
  of urine produced
• substances move from renal tubules into blood of
  peritubular capillaries
• glucose, water, urea, proteins, creatine
• amino, lactic, citric, and uric acids
• phosphate, sulfate, calcium, potassium, and
  sodium ions

• Tubular Secretion (TS) Adds to volume of urine
  produced
• substances move from blood of peritubular
  capillaries into renal tubules
• drugs and ions, urea, uric acid, H

? Urine formation GF TS - TR
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Glomerular Filtration
Glomerular filtrate is plasma that passes through
1) the fenestrae of the capillary endothelium,
2) the basement membrane around the endothelium,
and 3) the filtration slits (slit pores) of the
pedicels This is called the filtration membrane
Glomerular filtration is a mechanical process
based primarily on molecule size
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Glomerular Filtration and Urine Formation
Glomerular Filtration Rate (GFR) is directly
proportional to the net filtration pressure GFR ?
125 ml/min (180 L/day) Urine output is only 0.6
2.5 L per day (an average of about 1.8 L, or
about 1 of glomerular filtrate)
99 of filtrate is reabsorbed!!
Blood pressure is the most important factor
altering the glomerular hydrostatic pressure (and
NFP). A MAP fall of 10 will severely impair
glomerular filtration a fall of 15-20 will stop
it.
NFP HPg
(HPc OPg)
Net Filtration Pressure force favoring
filtration forces opposing filtration
(glomerular capillary ( capsular
hydrostatic pressure hydrostatic
pressure) glomerular capillary

osmotic pressure )
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Summary of Factors Affecting GFR
Factor Effect
Vasoconstriction
Afferent arteriole (? radius ? GFR) ? GFR
Efferent arteriole (? radius ? 1/GFR) ? GFR

Vasodilation
Afferent arteriole ? GFR
Efferent arteriole ? GFR

Increased capillary hydrostatic pressure ? GFR

Increased colloid osmotic pressure ? GFR

Increased capsular hydrostatic pressure ? GFR
Know this table its important!
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Three Major Ways of Regulating GFR

• 1) Autoregulation
• Maintains GFR despite changes in local blood
  pressure and blood flow (between 90 180 mm Hg
  mean systemic pressure)
• Myogenic (muscular) mechanism contraction of
  afferent arteriolar vascular smooth muscle when
  stretched (increased BP) relaxation occurs when
  BP declines
• Tubuloglomerular mechanism MD cells detect ?
  flow rate and/or ? osmolarity of filtrate in DCT
  -gt JG cells contract -gt afferent arteriole
  constricts -gt ? GFR

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Three Major Ways of Regulating GFR

• 2) Neural (Autonomic) Regulation
• Mostly sympathetic postganglionic fibers
  vasoconstriction of afferent arterioles ? GFR
  (conserves water, redirects blood to other
  organs)
• Stimulates juxtaglomerular apparatus to secrete
  renin
• May override autoregulatory mechanism at afferent
  arteriole
• 3) Hormonal Regulation
• Renin-angiotensin system ? ECF volume and BP
• Atrial Natriuretic Peptide (ANP) - ? GFR, ? fluid
  loss (dilates afferent arteriole, constricts
  efferent arteriole)

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Renin-Angiotensin System

• Renin is released by the juxtaglomerular
  apparatus due to
• 1) Decline of BP (Renin ? 1/Pressure)
• 2) Juxtaglomerular stimulation by sympathethic
  NS
• 3) Decline in osmotic concentration of tubular
  fluid at macula densa( Renin ? 1/NaCl )

(ACE)
Actions of Angiotensin II
Stabilizes systemic blood pressure and
extracellular fluid volume
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Tubular Reabsorption in PCT
65 of filtrate volume is reabsorbed in the PCT
8 mm Hg
? COP
Tubular fluid
Tubular reabsorption - reclaiming of substances
in filtrate by body (tubule ? blood)
Peritubular cap 1) Low hydrostatic pressure 2)
High COP 3) High permeability
All uric acid, about 50 of urea, and no
creatinine is reabsorbed
Renal threshold is the plasma level
(concentration) above which a particular solute
will appear in urine, e.g., 180 mg/dl
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Summary of Reabsorption and Secretion
    Nephron Loop (of Henle) Nephron Loop (of Henle)    
Process PCT Descending Ascending DCT Collecting duct
Reabsorption    Glucose, aa, protein, urea, uric acid, Na, Cl-, HCO3-   H2O  Na/Cl-, K(NO H2O)  Na/Cl-H2OHCO3-   H2O (only if ADH is present), urea
Secretion   CreatinineH Some drugs    Urea  -   H/KNH4  -
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Reabsorption in the PCT
Substance Mechanism of Reabsorption Notes
Na (Cl-) Primary Active Transport Na reabsorption is the driving force for most other reabsorption
H2O Osmosis Closely associated with movement of Na(Obligatory water reabsorption)
Glucose Secondary Active transport Limited of molecules can be handled (Tm 375 mg/min) attracts H20
Amino Acids Secondary Active transport Three different active transport modalities difficult to overwhelm
Other electrolytes Secondary Active transport
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Secretion in the PCT and DCT
In the DCT potassium ions or hydrogen ions may be
secreted in exchange for reabsorbed sodium ions.
Reabsorption of Na in the DCT is increased by
the hormone, aldosterone. Other compounds are
actively secreted as well, e.g., histamine,
ammonia, creatinine, penicillin, phenobarbital.
Active and Passive
Active
Renal threshold is the plasma level
(concentration) above which a particular solute
will appear in urine, e.g., 180 mg/dl
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Summary of Events in the Nephron

• Filtrate produced
• Reabsorption of 65 of filtrate
• Obligatory water reabsorption
• Reabsorption of Na and Cl- by active transport
  (NO H2O reabsorption)
• 5,6. Facultative reabsorption of water (ADH is
  needed)
• 7. Absorption of solutes and water by vasa recta
  to maintain osmotic gradient

(Aldosterone)
(Aldosterone)
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The Countercurrent Multiplier
Approximate normal osmolarity of body fluids
Reduced osmolarity of tubular fluid due to action
of counter-current multiplier
The mechanism shown is called the countercurrent
multiplier Countercurrent multiplier allows the
kidneys to vary the concentration of urine Vasa
recta maintains the osmotic gradient of the renal
medulla so the countercurrent multiplier can work
Figure from Martini, Anatomy Physiology,
Prentice Hall, 2001
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Urea,Uric Acid, and Diuretics

• Urea
• product of amino acid catabolism
• plasma concentration reflects the amount or
  protein in diet
• enters renal tubules through glomerular
  filtration
• 50 reabsorbed
• rest is excreted

• Uric Acid
• product of nucleic acid metabolism
• enters renal tubules through glomerular
  filtration
• 100 of filtered uric acid is reabsorbed
• 10 secreted and excreted

A diuretic promotes the loss of water in the
urine. Anything that adds more solute to
tubular fluid will attract H2O and can function
as a diuretic to increase the volume of urine,
e.g., glucose (osmotic diuretic)
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Urine

• Urine composition varies depending upon
• Diet
• Level of activity
• Major constituents of urine
• H2O (95)
• Creatinine (remember, NONE of this is reabsorbed)
• Urea (most abundant solute), uric acid
• Trace amounts of amino acids
• Electrolytes
• Urochrome (yellow color), urobilin, trace of
  bilirubin
• Normal urine output is 0.6-2.5 L/day (25-100
  ml/hr)
• Output below about 25 ml/hour kidney failure
  (oliguria -gt anuria)

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Terms to know

• Anuria absence of urine
• Diuresis increased production of urine
• Dysuria difficult or painful urination
• Enuresis uncontrolled (involuntary) urination
• Glycosuria (glucosuria) glucose in the urine
• Hematuria blood in the urine
• Oliguria scanty output of urine
• Polyuria excessive urine output

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Elimination of Urine
Flow of Urine

• nephrons
• collecting ducts
• renal papillae
• minor and major calyces
• renal pelvis
• ureters
• urinary bladder
• urethra
• outside world

Know this
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Ureters and Urinary Bladder
Urinary elimination system is lined mostly by
transitional epithelium
Ureters - retroperitoneal tubes about 25 cm
long - carry urine from kidneys to bladder by
peristaltic contractions
Urinary bladder (cysto) - temporary storage
reservoir for urine
Smooth muscular layer runs in all directions
(detrusor muscle) under parasympathetic control.
Contraction compresses the bladder and causes
urine to flow into urethra
Internal sphincter is thickening of detrusor
muscle at neck of bladder closed when detrusor
is relaxed open when detrusor contracts
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Urethra
Note the short urethra in females (about 4 cm)
Note the long male urethra (about 18-20 cm).
There are three sections to the male urethra -
Prostatic urethra - Membranous urethra -
Penile urethra
Figure from Saladin, Anatomy Physiology,
McGraw Hill, 2007
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Micturition (Urination) Reflex
Figure from Saladin, Anatomy Physiology,
McGraw Hill, 2007
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Fluid and Body Compartments
About 40 L of fluid (avg. adult male less in
females due to greater proportion of body fat)
(ICF)
? 25L
Major forces affecting movement of fluid between
compartments 1) Hydrostatic pressure 2)
Osmotic pressure
(ECF)
? 15L
Compartments commonly behave as distinct
entities in terms of ion distribution, but ICF
and ECF osmotic concentrations (about 290-300
mOsm/L) are identical. This is because H2O is
free to flow between compartments and any
disturbance in osmolarity is quickly corrected by
H2O movement.
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Body Fluid Ionic Composition
ECF major ions - sodium, chloride, and
bicarbonate ICF major ions - potassium,
magnesium, and phosphate (plus negatively charged
proteins)
You should know these chemical symbols and
charges of ions
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Fluid (Water) Balance

Balance
urine production is the most important
regulator of water balance (water in water out)
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Major Regulators of H2O Intake and Output

• Regulation of water intake
• increase in osmotic pressure of ECF ?
  osmoreceptors in hypothalamic thirst center ?
  stimulates thirst and drinking
• Regulation of water output
• Obligatory water losses (must happen)
• insensible water losses (lungs, skin)
• water loss in feces
• water loss in urine (min about 500 ml/day)
• increase in osmotic pressure of ECF ? ADH is
  released
• concentrated urine is excreted
• more water is retained
• LARGE changes in blood vol/pressure ? Renin and
  ADH release

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Dehydration and Overhydration

• Dehydration
• osmotic pressure increases in extracellular
  fluids
• water moves out of cells
• osmoreceptors in hypothalamus stimulated
• hypothalamus signals posterior pituitary to
  release ADH
• urine output decreases

• Overhydration
• osmotic pressure decreases in extracellular
  fluids
• water moves into cells
• osmoreceptors inhibited in hypothalamus
• hypothalamus signals posterior pituitary to
  decrease ADH output
• urine output increases

Drunken behavior (water intoxication),
confusion, hallucinations, convulsions, coma,
death
Severe thirst, wrinkling of skin, fall in plasma
volume and decreased blood pressure, circulatory
shock, death
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Osmolarity and Milliequivalents (mEq)

• Recall that osmolarity expresses total solute
  concentration of a solution (Osmolarity Amt of
  solute / Vol of H2O)
• Osmolarity (effect on H2O) of body solutions is
  determined by the total number of dissolved
  particles (regardless of where they came from)
• The term osmole reflects the number of
  particles yielded by a particular solute
  (milliosmole, mOsm, osmole/1000)
• 1 mole of glucose (180g/mol)
• 1 mole of NaCl (58g/mol)
• An equivalent is the positive or negative charge
  equal to the amount of charge in one mole of H
• A milliequivalent (mEq) is one-thousandth of an
  Eq
• Used to express the concentration of CHARGED
  particles in a solution

-gt 1 osmole of particles
-gt 2 osmoles of particles
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Electrolyte Balance

• Electrolyte balance is important because
• It regulates fluid (water) balance
• Concentrations of individual electrolytes can
  affect cellular functions

Electrolyte Normal plasmaconcentration (mEq/L) Major mechanism(s) regulating retention and loss
Na 140 1. Renin-angiotensin pathway 2. Aldosterone (Angiontensin II, Na, K) 3. Natriuretic peptides
Cl- 105 Follows Na
K 4.0 1. Secretion at DCT (aldosterone sensitive)
Ca2 5.0 1. Calcitonin (children mainly) 2. Parathyroid hormone 3. Vitamin D (dietary uptake from intestines)
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Summary Table of Fluid and Electrolyte Balance
Condition Initial Change Initial Effect Correction Result
Change in OSMOLARITY (Corrected by change in H2O levels) ? H2O in the ECF ? Na concentration, ? ECF osmolarity ? Thirst ? ? H2O intake ? ADH ? ? H2O output ? H2O in the ECF
Change in OSMOLARITY (Corrected by change in H2O levels) ? H2O in the ECF ? Na concentration, ? ECF osmolarity ? Thirst ? ? H2O intake ? ADH ? ? H2O output ? H2O in the ECF
Change in VOLUME (Corrected by change in Na levels) ? H2O/Na in the ECF ? volume, ? BP Renin-angiotensin ? Thirst ? ADH ? aldosterone? vasoconstriction ? H2O intake ? Na/H2O reabsorption ? H2O loss
Change in VOLUME (Corrected by change in Na levels) ? H2O/Na in the ECF ? volume, ? BP Natriuretic peptides ? Thirst ? ADH ? aldosterone ? H2O intake ? Na/H2O reabsorption ? H2O loss
You should understand this table
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Acid/Base Buffers
A buffer resists changes in pH
Buffer Type Speed Eliminate H from body? Examples
Chemical Physical(first line of defense) Seconds No Bicarbonate, phoshate, proteins (ICF, plasma proteins, Hb)
Respiratory Physiological Minutes Yes (indirectly as CO2) H2O CO2 ? ? H HCO3-
Renal Physiological Hours - Days Yes H excretion HCO3- excretion/retention
Normal plasma HCO3- 25 mEq/L
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Acidosis and Alkalosis
If the pH of arterial blood drops to 6.8 or rises
to 8.0 for more than a few hours, survival is
jeopardized

• Classified according to
• Whether the cause is respiratory (CO2), or
  metabolic (other acids, bases)
• Whether the blood pH is acid or alkaline

Respiratory system compensates for metabolic
acidosis/alkalosisRenal system compensates for
respiratory acidosis/alkalosis