2015: Biological Systems 1: INTER 131
Body Fluid/Electrolytes and Kidney System - 1 Credit Hour
November 20, 2015 – December 9, 2015
Monday, Wednesday, Friday 9:00 - 11:00 am lectures
Location: Medical Education Bldg, 3rd Floor, Seminar Rm #4
Section Director:
Section Co-Director:
Faculty:
Lisa M. Harrison-Bernard, PhD; lharris@lsuhsc.edu
Associate Professor, Department of Physiology
Daniel R. Kapusta, PhD; dkapus@lsuhsc.edu
Professor, Department of Pharmacology
Joseph B. Delcarpio, PhD; jdelca@lsuhsc.edu
Professor, Cell Biology and Anatomy
Richard E. Tracy, MD, PhD; rtracy@lsuhsc.edu
Professor Emeritus, Pathology
Course Schedule
DAY/DATE
TIME am
PROFESSOR
TOPIC
Fri, Nov 20
9:00
10:00
Delcarpio
Harrison-Bernard
Organization of the Urinary System
Body Fluid Compartments, Renal Clearance and
Renal Excretion of Drugs
Mon, Nov 23
9:00
10:00
Harrison-Bernard
Harrison-Bernard
Glomerular Filtration
Renal Blood Flow
Wed, Nov 25
No Class
No Class
No Class
Fri, Nov 27
HOLIDAY
HOLIDAY
THANKSGIVING HOLIDAY
Mon, Nov 30
9:00
10:00
Harrison-Bernard
Harrison-Bernard
Quiz 1
Renal Problem Set Student Presentations
Transport of Acids and Bases
Wed, Dec 2
9:00
10:00
Fri, Dec 4
9:00
10:00
9:00
Mon, Dec 7
10:00
Wed, Dec 9
9:00-11:00
Renal Physiology Block
Kapusta
Kapusta
Kapusta
Kapusta
Transport of Sodium and Chloride
Transport of Urea, Glucose, Organic Solutes,
and Potassium
Quiz 2
Urine Concentration and Dilution
Pharmacology of Diuretics
Regulation of Sodium and Water Balance
Tracy
Harrison-Bernard
Quiz 3
Renal Pathology
Renal Failure Patient
EXAM
Body Fluid/Electrolytes and Kidney Systems
Page 1 of 18
Textbook
The recommended text for this course is "Renal Physiology”, 4th or 5th Edition, The Mosby
Physiology Monograph Series by Koeppen and Stanton, and is available for purchase in the
LSUHSC bookstore. ISBN-13 978-0-323-03447-0
Examination
One examination will be given which will consist of approximately 5 multiple choice questions
per lecture hour.
Overall Learning Objectives
1.
Describe in sequence the tubular segments through which ultrafiltrate flows after it is
formed at Bowman’s capsule to when it enters the renal pelvis. Identify each structure
as being located in the renal cortex or renal medulla. Based on the glomerulus location
and the length of the loop of Henle, distinguish between cortical and juxtamedullary
nephrons.
2.
Given the body weight estimate the a) total body water, b) extracellular fluid volume, c)
intracellular fluid volume, d) blood volume, and e) plasma volume. Identify normal
extracellular fluid (plasma) osmolarity and concentrations of Na+, K+, Cl- and contrast
these values with those for intracellular fluids.
3.
Using the volumes/compartments identified in objective 2, contrast the movement
between intracellular and extracellular compartments caused by increases or decreases
in extracellular fluid osmolality.
4.
Explain the clearance principle. Use the clearance equation and an appropriate
compound to estimate the glomerular filtration rate, renal plasma flow, and renal blood
flow.
5.
Given the capillary and Bowman’s capsule hydrostatic and oncotic pressures, calculate
the net filtration force at the glomerular capillaries. Predict the changes in glomerular
filtration caused by increases or decreases in any of those pressures.
6.
Describe the relative resistances of the afferent and efferent arterioles and the effects on
renal blood flow and GFR of selective changes in each.
7.
Describe the contribution of the major nephron segments to the reabsorption of the
filtered load of solute and water.
8.
Describe the nephron sites and molecular mechanisms of action of the following classes
of diuretics (osmotic, carbonic anhydrase inhibitors, loop, thiazide, K+-sparing).
9.
Identify the two most powerful stimuli that cause ADH release, and describe the negative
feedback control mechanisms for each.
10.
Diagram the formation and generation of angiotensin II, beginning with renin. Identify
four factors that can promote renin release.
Renal Physiology Block
Page 2 of 18
11.
Describe the regulation of Na+ reabsorption along the nephron, including the effects of
sympathetic nerves, angiotensin II, aldosterone, and atrial natriuretic peptide.
12.
Describe net acid excretion by the kidneys, titratable acid, the importance of urinary
buffers, and the production and excretion of ammonium. Distinguish between the
reclamation of filtered bicarbonate and the formation of new bicarbonate by the kidney.
13.
Understand the common symptoms and treatments for patients suffering from chronic
renal failure.
Renal Physiology Block
Page 3 of 18
Integrative Sciences: Biological Systems B
Body Fluid/Electrolytes and Kidney Systems
Organization of the Urinary System
Lecturer:
Joseph B. Delcarpio, PhD
Reading:
Chapters 2 in Koeppen & Stanton Renal Physiology (Mosby
Physiology Monograph Series)
Learning Objectives:
1.
Gain insight into the kidney adaptations to arid environments
2.
Know the location of the kidneys, gross anatomic features, and components
3.
Know the nephron and tubular nomenclature and the locations within the cortex
and medulla
4.
Know the components of the renal corpuscle and the cell types located in each
component
5.
Describe which structures in the glomerulus are filtration barriers to plasma
proteins
6.
Describe the physiological significance of the juxtaglomerular apparatus
7.
Understand the blood supply to the kidneys
Renal Physiology Block
Page 4 of 18
Integrative Sciences: Biological Systems B
Body Fluid/Electrolytes and Kidney Systems
Body Fluids Compartments, Renal Clearance and Renal Excretion of Drugs
Lecturer:
Lisa M Harrison-Bernard, PhD
Reading:
Chapters 1 & 3 in Koeppen & Stanton Renal Physiology (Mosby
Physiology Monograph Series)
Learning Objectives:
1.
Given the body weight, estimate the a) total body water, b) extracellular water, c)
intracellular water, d) blood volume, and e) plasma volume. Identify normal
extracellular fluid (plasma) osmolarity and concentrations of Na+, K+, Cl-, HCO3,
proteins, creatinine, and contrast these values with those for intracellular fluids.
2.
Predict the changes in extracellular fluid volume, extracellular fluid osmolality,
intracellular fluid volume, and intracellular fluid osmolality caused by intravenous
infusion of three liters of 0.9% NaCl (isotonic), 0.45% NaCl (hypotonic), and 7.5%
NaCl (hypertonic).
3.
Explain the clearance principle. Use the clearance equation and an appropriate
compound to estimate the glomerular filtration rate (GFR), renal plasma flow
(RPF), and renal blood flow (RBF).
4.
Given the appropriate plasma and urine concentrations and the urine flow,
calculate the filtered load, tubular transport, and excretion rate of a given
compound. Given the appropriate plasma and urine concentrations and the urine
flow, calculate the clearance of inulin, creatinine, para-amino hippuric acid (PAH),
and glucose. Predict how changes in filtration, reabsorption, and secretion will
affect renal excretion of each compound.
Renal Physiology Block
Page 5 of 18
Integrative Sciences: Biological Systems B
Body Fluid/Electrolytes and Kidney Systems
Renal Blood Flow and Glomerular Filtration
Lecturer:
Lisa M Harrison-Bernard, PhD
Reading:
Chapter 3 in Koeppen & Stanton Renal Physiology (Mosby
Physiology Monograph Series)
Learning Objectives:
1.
Describe how the Starling hypothesis of capillary exchange applies to the
glomerular capillaries and the process of glomerular filtration. Describe typical
values of the Starling forces and how changes in them would affect glomerular
filtration.
2.
Describe how the Starling hypothesis of capillary exchange applies to the
peritubular capillaries and the process of fluid reabsorption. Describe typical
values of the Starling forces and how changes in them would affect the rate of
fluid reabsorption.
3.
List the 3 components of the glomerular filtration barrier and describe their
relative contribution to the composition of the glomerular filtrate.
4.
Define the filtration coefficient at the glomerular capillary and explain its role in
determining glomerular filtration rate.
5.
Given the capillary and Bowman’s capsule hydrostatic and oncotic pressures,
calculate the net filtration force at the glomerular capillaries. Predict the changes
in glomerular filtration caused by increases or decreases in any of those
pressures.
6.
Define renal blood flow, plasma flow, glomerular filtration rate, and filtration
fraction.
7.
Know the average values for renal blood flow and glomerular filtration rate in
adult humans. Compare kidney blood flow and oxygen consumption to that of
skeletal muscle.
8.
Describe the relative resistances of the afferent and efferent arterioles and the
effects on renal blood flow and glomerular filtration rate of selective changes in
each.
9.
Define and describe autoregulation of renal blood flow and glomerular filtration
rate.
10.
Define and describe the myogenic and tubuloglomerular feedback mechanisms
Renal Physiology Block
Page 6 of 18
that mediate the autoregulation of renal blood flow and glomerular filtration rate.
11.
Predict the changes in renal blood flow and glomerular filtration caused by: a)
increased synthesis of angiotensin II, b) increased release of atrial natriuretic
peptide, c) increase in renal sympathetic nerve activity, d) increase secretion of
arginine vasopressin, and e) increased prostaglandin formation, f) increased
nitric oxide formation.
12.
Know the effects of hormones, paracrine factors and autocoids on the resistance
of afferent and efferent arterioles.
Renal Physiology Block
Page 7 of 18
Renal Physiology Block
Page 8 of 18
Integrative Sciences: Biological Systems B
Body Fluid/Electrolytes and Kidney Systems
Problem Set
Complete the Problem Set on Your Own. The key will be posted on June 2.
I.
Body Fluid Problems - Shifts of water between compartments
What is the direction of change (↔, , ↓) after equilibration for the following 7
parameters?
1.
2.
3.
4.
5.
6.
7.
Volume of Total Body Water (TBW)?
Total Body Osmolality?
Extracellular Fluid (ECF) Osmolality?
Extracellular Fluid (ECF) Volume?
Intracellular Fluid (ICF) Volume?
Plasma protein concentration (PPC)?
Arterial blood pressure (BP)?
A.
Infusion of isotonic NaCl (isosmotic volume expansion)
B.
Diarrhea - loss of isotonic fluid (isosmotic volume contraction)
C.
Excessive NaCl intake - addition of NaCl (hyperosmotic volume expansion)
D.
Sweating in a desert - loss of water (hyperosmotic volume contraction)
E.
Syndrome of inappropriate antidiuretic hormone (SIADH) - gain of water
(hypoosmotic volume expansion)
F.
Adrenocortical insufficiency - loss of NaCl (hypoosmotic volume
contraction)
Renal Physiology Block
Page 9 of 18
TBW
TBW
ECF
ECF
ICF
PPC
Blood
(L)
Osmolality
Volume
Osmolality
Volume
(g%)
Pressure
(mosmol/kg
(L)
(mosmol/kg
(L)
H20)
(mmHg)
H20)
A
B
C
D
E
F
Renal Physiology Block
Page 10 of 18
II.
Starling Forces
1.
At the afferent arteriolar end of a glomerular capillary, PGC is 45 mmHg,
PBS is 10 mmHg, and  GC is 27 mmHg.
What are the value and direction of the net ultrafiltration pressure?
III.
Renal Clearance, Renal Blood Flow, Glomerular Filtration Rate, etc.
2.
To measure GFR:
Infuse inulin intravenously until PIN is stable. Measure urine volume produced in
a known period of time (urine flow). Measure PIN and UIN.
Given the following:
PIN = 0.5 mg/ml
UIN = 60 mg/ml
Urine flow = 1.0 ml/min
What is GFR?
3.
To measure CPAH:
Infuse PAH. Obtain a timed, complete urine collection and a blood sample.
Measure PPAH, UPAH, and urine flow.
Renal Physiology Block
Page 11 of 18
Given the following:
PPAH = 0.05 mg/ml
UPAH = 29.5 mg/ml
Urine flow = 1.0 ml/min
What is CPAH?
4.
Calculation of Renal Blood Flow (RBF): RBF = RPF  (1–Hct )
Given the following:
Hematocrit = 0.45
RPF calculated in problem #3
What is RBF = ?
5.
Calculation of Filtration Fraction (FF): Fraction (%) of renal plasma flow
that is filtered (moves across the glomerular capillary walls into the
Bowman's space) as blood traverses the kidney. FF = GFR  RPF
Given the GFR and RPF calculated in problems #2 and #3, what is FF = ?
6.
Creatinine is a substance that is excreted primarily by filtration and is
produced by the body at a fairly constant rate. Thus, it can be used to
estimate glomerular filtration rate (GFR).
Given the following data:
24 hour urine volume = 1.2 liters
UCr = 144 mg/100 ml
PCr = 2 mg/100 ml
6A. Calculate the GFR.
6B. Is this value below normal, normal, or above normal?
7.
In many experimental studies, inulin is used to measure GFR because it is
easily measured and only filtered. Also, PAH is used to estimate the
plasma flow because the kidney extracts it from plasma very efficiently.
Given the following data:
urine flow = 3 ml/min
PIN = 0.22 mg/ml
UIN = 9.5 mg/ml
PPAH = 0.08 mg/ml
UPAH = 20 mg/ml
7A. Calculate the GFR and PAH clearances.
7B. Calculate the filtration fraction.
7C. If the hematocrit is 0.40, what is the total renal blood flow?
Integrative Sciences: Biological Systems B
Body Fluid/Electrolytes and Kidney Systems
Transport of Sodium Chloride
Lecturer:
Daniel R. Kapusta, Ph.D.
Reading:
Chapters 4, 7, and 10 in Koeppen & Stanton Renal Physiology
(Mosby Physiology Monograph Series)
Learning Objectives:
1.
Know the renal processes involved in the formation of urine.
2.
Describe the contribution of the major nephron segments to the reabsorption of
the filtered load of solute and water.
3.
Describe the cellular mechanisms involved in the transport of Na+, Cl- and water
by each of the major tubular segments.
4.
Describe the pathways involved in the renal tubular reabsorption of filtered
bicarbonate and glucose in the proximal tubules.
5.
Understand the principle of osmotic diuresis as applies to the drug mannitol and
hyperglycemia. Understand the urinary effects caused by inhibition of carbonic
anhydrase inhibitor diuretics.
6.
Describe the transporter responsible for Na reabsorption in the thick ascending
limb and its importance in the action of loop diuretics.
7.
Describe the transporter responsible for Na reabsorption in the early distal
convoluted tubules and its importance in the action of thiazide diuretics.
8.
Describe the transporters responsible for Na reabsorption and potassium
secretion in the late distal tubule and how aldosterone can influence transporter
activity. Understand how these pathways can be altered by potassium-sparing
diuretics.
9.
Describe the mechanism by which vasopressin (antidiuretic hormone) alters
water transport in the collecting duct and how ‘water diuretics’ alter this process.
Integrative Sciences: Biological Systems B
Body Fluid/Electrolytes and Kidney Systems
Urine Concentration and Dilution
Lecturer:
Daniel R. Kapusta, Ph.D.
Reading:
Chapters 5 and 6 in Koeppen & Stanton Renal Physiology (Mosby
Physiology Monograph Series)
Learning Objectives:
1.
Know the renal processes involved in the concentration and dilution of urine.
2.
Explain how the transport and permeability characteristics of the descending and
ascending segments of the loop of Henle enable the kidneys to produce
concentrated urine.
3.
Describe how the renal tubular handling of urea contributes to the production of
concentrated urine. Know that urea is filtered, reabsorbed and secreted and that
urea recycling is responsible for the buildup of high [urea] in the inner medulla.
4.
Explain how the transport and permeability characteristics of the early and late
convoluted tubules enable the kidneys to produce dilute urine.
5.
Describe the mechanism by which AVP alters the water permeability of the
collecting duct.
6.
Explain the effect of changes in the water permeability of the collecting duct on
the volume and composition of the final urine.
7.
Describe the site and mechanism of AVP secretion.
8.
Identify the two most powerful stimuli that cause ADH release, and describe the
negative feedback control mechanisms for each.
9.
Identify the tubular section and cellular mechanism by which ADH increases
permeability to water and urea. Describe the role of these changes on the ability
of the kidney to produce either dilute or concentrated urine.
10.
Know the pathology features involving AVP secretion (SIADH, central diabetes
insipidus), and renal function (nephrogenic diabetes insipidus).
11.
Know steps in the formation and generation of angiotensin II, beginning with
renin. Identify conditions that can increase or decrease the secretion of renin
and consequently the formation of angiotensin II. Understand the physiological
responses produced by angiotensin II-induced activation of AT1 and AT2
receptors.
12.
Explain how the renin-angiotensin-aldosterone system can affect sodium
reabsorption, total body sodium/water balance, and regulation of blood pressure.
13.
Explain the mechanism of action of aldosterone and how this hormone can
influence total body sodium/water balance and blood pressure regulation.
14.
Describe the sensors involved in the monitoring of ECF volume (e.g., highpressure baroreceptors and low-pressure cardiopulmonary stretch receptors),
and diagram the neural reflex regulation of renal Na+ and water excretion
15.
Explain how the effectors that control ECF target renal sodium excretion,
whereas the effectors that control osmolality target thirst and renal water
excretion.
16.
Explain how the baroreflex is involved in the rapid regulation of systemic arterial
blood pressure and vasopressin secretion.
17.
Understand the integrated neural and humoral control of total body water and
sodium balance; and regulation of arterial blood pressure.
Integrative Sciences: Biological Systems B
Body Fluid/Electrolytes and Kidney Systems
Transport of Acids and Bases
Lecturer:
Lisa M. Harrison-Bernard, Ph.D.
Reading:
Chapter 8 in Koeppen & Stanton Renal Physiology (Mosby
Physiology Monograph Series)
Learning Objectives:
1.
Identify the normal range of pH values, and the upper and lower limits compatible
with life. Describe the role of buffers in maintaining pH, including the roles of the
lungs and kidneys.
2.
Distinguish between CO2-derived (volatile acid) and nonvolatile acids, the relative
amounts produced each day through dietary intake and cellular metabolism, and
the normal routes of loss from the body.
3.
Explain the four “simple” types of acid-base disorders (metabolic acidosis and
alkalosis, and respiratory acidosis and alkalosis) and the direction of changes in
HCO3-, CO2, and pH in each disorder.
4.
Explain the compensatory mechanisms following acid-base disorders.
5.
Calculate the filtered load of HCO3-, and identify the major sites of reabsorption
(and secretion) along the nephron, emphasizing the importance of H + secretory
mechanisms in this process. Describe the cellular mechanisms responsible for
net transepithelial movement of HCO3-.
6.
Describe net acid excretion by the kidneys, titratable acid, the importance of
urinary buffers, and the production and excretion of ammonium. Distinguish
between the reclamation of filtered bicarbonate and the formation of new
bicarbonate by the kidneys.
7.
Describe processes that lead to acid-base disturbances and list common causes.
Integrative Sciences: Biological Systems B
Body Fluid/Electrolytes and Kidney Systems
Renal Failure Patient
Lecturer:
Lisa M. Harrison-Bernard, Ph.D.
Reading:
Koeppen & Stanton Renal Physiology (Mosby Physiology Monograph
Series) Pink Text Boxes Labeled “In the Clinic”
Learning Objectives:
1.
Have an understanding of the normal values for glomerular filtration rate in
humans.
2.
Be able to explain why serum creatinine is a diagnostic tool for physicians.
3.
Be familiar with the most common causes of kidney failure.
4.
Be able to predict the directional changes in the components of serum and blood
in patients with chronic renal failure.
5.
Understand the goal of the treatment of symptoms of chronic renal failure.
6.
Be able to explain the 3 treatment options for end-stage renal disease.
7.
Have a general knowledge of other forms of renal disease.