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Review slides

Lecture Exam 3

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Overview of the Endocrine SystemThe 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

Hormones

Eicosanoids (cell membranes)(locally acting)

Steroids (cholesterol-derived)

Amino Acid Derivatives

Amino acids

Peptides

Proteins, glycoproteins

Lipid Derived

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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->Na/K Pump

Magnitude of cellular response proportional to the number of hormone-receptor complexes formed

(Thyroid hormone has a similar mechanism of action, even though it is a tyrosine derivative)

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Actions of Amino Acid-Derived Hormones

• 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 – it’s amplified

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

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Control of Hormonal Secretions

• primarily controlled by negative feedback mechanism

1) Hormonal 2) Neural 3) Humoral

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)

Tropic hormones control the activity of other endocrine glands

All anterior pituitary hormones use second messengers

(an ‘axis’)

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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 HormonesTissue

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 productionfemales: 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 secretionfemales: ovulation

Gonadotropin Releasing Hormone (GnRH)

THYROID STIMULATING

HORMONE (TSH)

anterior pituitary

thyroid secrete hormonesThyrotropin Releasing

Hormone (TRH)

GROWTH HORMONE (GH)

anterior pituitary

bone, muscle, fat growth of tissuesGrowth Hormone Rleasing

Hormone (GHRH)

ADRENOCORTICO-TROPIC HORMONE

(ACTH)

anterior pituitary

adrenal cortex secrete adrenal hormonesCorticotropin Releasing

Hormone (CRH)

PROLACTIN (PRL)anterior pituitary

mammary glands produce milkProlactin 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 letdownStretching of uterus; infant

suckling

Se(x)

T

G

A

P

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Hormone Summary Table IITissue

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)

ParathyroidsIntestine, 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 CortexKidneys; 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 cellsDiabetogenic; anti-inflammatory

(glucocorticoid)ACTH

INSULINβ-cells of

Pancreatic Isletsall cells, liver and skeletal muscle

pushes glucose into cells from blood, glycogen formation (decreases blood glucose)

plasma [glucose]SNS

GLUCAGONα-cells of

pancreatic Isletsliver and skeletal

musclebreakdown of glycogen (increase in blood

glucose) plasma [glucose]

TESTOSTERONE Testessecondary sex

organsdevelopment and maintenance LH

ESTROGEN Ovariessecondary sex

organsdevelopment at puberty and maintenance

throughout lifeLH

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 StressExhaustion - 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 P’s 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

Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001

Helps maintain position of kidney

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

Nephrons are the structural and functional units of the kidney

(80%)

(20%)Vasa recta are associated with juxtamedullary nephrons

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

Filtrate in capsular space

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)

The order of the parts of the nephron is important to know

(PCT)

(DCT)

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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

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.

(1.8 L/day)

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Urine Formation

• 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

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)

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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)

Net Filtration Pressure = force favoring filtration – forces opposing filtration (*glomerular capillary ( capsular hydrostatic pressure hydrostatic pressure) + glomerular capillary osmotic pressure )

NFP = HPg – (HPc + OPg)

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.

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Summary of Factors Affecting GFRFactor Effect

Vasoconstriction

Afferent arteriole (Δ radius GFR) GFR

Efferent arteriole (Δ 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 – it’s 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 -> JG cells contract -> afferent arteriole constricts -> 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] )

Stabilizes systemic blood pressure and extracellular fluid volume

(ACE)

Actions of Angiotensin II

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Tubular Reabsorption in PCT

65% of filtrate volume is reabsorbed in the PCT

8 mm Hg

COP

Tubular fluid

All uric acid, about 50% of urea, and no creatinine is reabsorbed

Tubular reabsorption - reclaiming of substances in filtrate by body (tubule blood)

Peritubular cap: 1) Low hydrostatic pressure 2) High COP 3) High permeability

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)    

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

 Creatinine

H+

Some drugs 

 

Urea  -  H+/K+

NH4+  -

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Reabsorption in the PCTSubstance Mechanism of

ReabsorptionNotes

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 DCTIn 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.

ActiveActive and Passive

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 Nephron1. Filtrate produced

2. Reabsorption of 65% of filtrate

3. Obligatory water reabsorption

4. 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

Figure from: Martini, Anatomy & Physiology, Prentice Hall, 2001

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

Approximate normal osmolarity of body fluids

Reduced osmolarity of tubular fluid due to action of counter-current multiplier

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Urea,Uric Acid, and DiureticsUrea

• 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 -> 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

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

Flow of Urine

Know this…

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Ureters and Urinary Bladder

Ureters - retroperitoneal tubes about 25 cm long - carry urine from kidneys to bladder by peristaltic contractions

Urinary bladder (cyst[o]) - temporary storage reservoir for urineSmooth 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

Urinary elimination system is lined mostly by transitional epithelium

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Urethra

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

Note the short urethra in females (about 4 cm)

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Micturition (Urination) Reflex

Figure from: Saladin, Anatomy & Physiology, McGraw Hill, 2007

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Fluid and Body Compartments

‘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.

About 40 L of fluid (avg. adult male; less in females due to greater proportion of body fat)

25L

15L

Major forces affecting movement of fluid between compartments:

1) Hydrostatic pressure 2) Osmotic pressure

(ICF)

(ECF)

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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

* urine production is the most important regulator of water balance (water in = water out)

Balance; =

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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 OverhydrationDehydration

• 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

-> 1 osmole of particles

-> 2 osmoles of particles

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Electrolyte BalanceElectrolyte balance is important because:

1. It regulates fluid (water) balance

2. Concentrations of individual electrolytes can affect cellular functions

ElectrolyteNormal plasma

concentration (mEq/L)

Major mechanism(s) regulating retention and loss

Na+ 140 1. Renin-angiotensin pathway2. 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 hormone3. 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

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

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

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+ excretionHCO3

- excretion/retention*

A buffer resists changes in pH

*Normal plasma [HCO3-] ≈ 25 mEq/L

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Acidosis and AlkalosisIf 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:

1. Whether the cause is respiratory (CO2), or metabolic (other acids, bases)

2. Whether the blood pH is acid or alkaline

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