1
QUIZ/TEST REVIEW NOTES
SECTION 2 RENAL PHYSIOLOGY FILTRATION
[THE KIDNEYS/URINARY SYSTEM]
CHAPTER 19
I.
REABSROPTION OVERVIEW
a.
b.
c.





Learning Objectives:

Differentiate the following processes:
filtration, reabsorption, secretion,
excretion

Explain how the structure of the
glomerulus promotes and limits
filtration

Describe the factors that influence
GFR and the processes involved in its
regulation

Explain how creatinine clearance is
determined and describe its clinical
significance
More then 99% of the fluid entering the tubules must be reabsorbed into the blood as filtrate moved
through the nephrons
Most reabsorption takes place in the proximal tubule, with smaller amounts in the distal segments
i. Regulated reabsorption by hormones in the distal nephron allows kidneys to return ions and
water to the plasma selectively – as needed to maintain homeostasis
Reabsorption may be a Active or Passive
i. Water and ions in the proximal tubule have the same solute concentrations as the extracellular
fluid, so to move out of tubule cells must use active transport to create concentration or
electrochemical gradients
ii. DIAGRAM: General Overview of Tubular Reabsorption
Active transport of Na+ from tubule men to ECF creates transepithelial electrical gradient in which lumen is more
negative than the ECF
+
Anions then follow the positively charged Na out of the lumen
+
Net movement of Na and anions from lumen to ECF causes water to follow by osmosis
+
2+
Loss of volume from lumen increases the concentration of solutes (K , Ca , Urea) left behind in the filtrate
o Unchanged amount of solute in a smaller volume produces an increase concentration
Once luminal solute concentrations are higher than solute concentrations in the ECF, the solutes are free to diffuse
out of the lumen if the epithelium of the tubule is permeable to them
II. PASSIVE FOLLOWED BY ACTIVE; TRANSPORT OF SODIUM
a.
b.
c.
Active transport of Na+ is the primary driving force for most renal reabsorption
Filtrate entering proximal tubules has a similar ion composition with plasma
Filtrate has higher Na+ concentration then proximal tubule cells that separate tubule lumen and interstitial
fluid of the peritubular capillaries
2
d.
i. Na+ can thus enter tubule cells passively by moving down its electrochemical gradient
+ +
+
ii. In proximal tubule Na -H Antiporter players major role in Na reabsorption
+
One inside tubule cell Na is actively transported out across basolateral membrane by Na+-K+-ATPase
III. SECONDARY ACTIVE TRANSPORT: Symport with Sodium
a.




Sodium-linked secondary active transport
i. Sodium binds with other organic metabolite to help transport across tubule into interstitial fluid
ii. Responsible for glucose, amino acid, ion, and various organic metabolite reabsorption
iii. DIAGRAM: Sodium-linked glucose reabsorption in proximal tubule
Na+-dependent glucose reabsorption across proximal tubule epithelium
+
+
Proximal tubule cell apical membrane contains (SGLT) Na -glucose co-transporter that harnesses the energy of Na for
use by Glucose to diffuse
Na+ is then pumped from proximal tubule cell to interstitial fluid by Na+-K+-ATPase
Glucose is then pumped from proximal tubule cell to interstitial fluid by GLUT transporters
3
IV. UREA: PASSIVE REABSORPTION
a.
b.
c.
Urea: nitrogenous waste product
No active transporters in proximal tubule but will move across epithelium by diffusion if there is a urea
+
concentration gradient [gradient usually created by active transport of Na and other solutes]
Process:
i. When Na+ and other solutes are reabsorbed from the proximal tubule the transfer of osmotically
active particles makes the ECF more concentrated than the filtrate remaining in the lumen
ii. As a response to the osmotic gradient, water moves by osmosis from tubule lumen to ECF
iii. When H2O leaves lumen for ECF the filtrate concentration of urea increases because the same
amount of urea is contained in a smaller volume
iv. Once concentration gradient for urea exists, urea diffuses out of lumen in to ECF
V. SATURATION
a.
Saturation of Renal Transport Plays an Important Role in Kidney Function
i. Saturation refers to maximum rate of transport that occurs when all available carriers are
occupied by a substrate
ii. The transport rate at saturation is the transport maximum (TM) [mg/min]
1. Transport maximum is the maximum rate at which 100% of a substance can be
reabsorbed
iii. Ex: Glucose Reabsorption
1. Normal plasma glucose concentrations, all glucose that enters the nephron is
reabsorbed before it reaches end of proximal tubule
2. If person has diabetes mellitus, or excessive blood glucose concentrations, glucose is
filtered faster than the carriers of the peritubular capillaries can reabsorb it
a. Result: Glucose escapes reabsorption and is excreted in the urine
b. The plasma concentration at which glucose first appears in the urine is called
the renal threshold [mg/min] for glucose
Calculations
a) GFR x plasma concentration =
filtration rate
b) GFR x renal threshold = TM



Transport rate of a substance is proportional to the plasma concentration of the substance up to the point at which
transporters become saturated
Once saturation occurs transport rate reaches a maximum (T M)
The plasma concentration of substrate at which the (TM) occurs is called the renal threshold
Excretion = Filtration (increasing) – Reabsorption (constant)
VI.
PERITUBULAR CAPILLARY PRESSURES FAVORS REABSORPTION
a.
Drive force for reabsorption from the interstitial fluid into the capillaries is the low hydrostatic pressure that
exists along the entire length of the peritubular capillaries
i. Peritubular capillaries have hydrostatic pressure [blood pressure; opposes movement of fluid into
peritubular capillaries] of 10 mm Hg (in contrast to glomerular capillary hydrostatic pressure
which is 55 mm Hg)
ii. Colloid osmotic pressure (favors movement of fluid into peritubular capillaries) is 30 mm Hg
1. RESULT: Pressure gradient is 20 mm Hg in favor of absorption of fluid into capillaries
a. Fluid that is reabsorbed then passes from capillaries to venous circulation and
returns to the heart
4
VII. FLUID/ELECTROLYTE HOMEOSTATIC BALANCE
a.
b.
c.
d.
e.
f.
In the coarse of a day we consume roughly 2 liters of food and 6-15 grams of NaCl
i. Also bring in various electrolytes including K+, H+, Ca2+, HCO -3 and phosphate (HPO2-4)
THIRST: critical because drinking is only normal way to replace lost water
SALT APPETITE: critical behavior that leads people to seek and ingest salt (sodium chloride NaCl)
Importance of
+
i. H2O and Na : Associated with ECF volume and osmolarity
+
ii. K : Inbalances can cause serious problems with cardiac and muscle function
2+
iii. Ca : Variety of body processes, from Exocytosis and muscle contraction to bone formation and
blood clotting
+
iv. H and HCO 3: Ions whose balance determines body pH
ECF Osmolarity Affects Cell Volume
i. If osmolarity of ECF changes water moves into or out of cells and changes intercellular volume
ii. If ECF osmolarity decreases (result of excess water intake)  water moves into cells and they
swell
iii. If ECF osmolarity increases (result of salt intake)  water moves into cells and they shrink
1. Shrinking or swelling (changes in cell volume) can impair cell function
2. Ex: Swelling cells  ion channels in membrane open  disrupts membrane potential
and cell signaling
Fluid and Electrolyte Balance Requires Integration of Multiple Systems
i. Fluid and electrolyte balances is integrative because it involves cardiovascular and respiratory
systems, and renal and behavioral responses
1. Rapid Responses performed by:
a. Lungs
Under Neural Control
b. Cardiovascular system
2. Slow Responses performed by:
a. Kidneys
Under Endocrine and
neuroendocrine
control
CAPATION: The Body’s Integrated Responses to Changes in Blood Volume and Blood Pressure
5
WATER BALANCE OSMOSIS EXPLAINED
a.
b.
c.
d.
Water Distribution
rd
a.
Plasma: 8%
Plasma (effects)  3 space (effects)
rd
b.
Interstitial Tissue: 25% [tissue fluid/external fluid/3 space]
intracellular space
c.
Intracellular Fluid: 67%
Tonicity and Cell Volume
Osmosis: Water
a.
Effect of cell in isotonic environment: No Change
movement from low
b.
Effect of cell in hypertonic environment: Cell shrinks/dehydrates
gradient to high
c.
Effect of cell in hypotonic environment: Cell swells/rehydrates
gradient
IV Fluid Therapy
a.
Blood volume/pressure therapy
i. Isotonic solution
b.
Rehydration therapy
i. Hypotonic solution
c.
Tonicity
d.
Salt content determines water movement
Volume-Osmolarity Challenges
a.
Sensors
i. Volume receptors
=
Atria of heart
ii. Baroreceptors
=
Carotid arteries and aortic arch
iii. Osmoreceptors
=
Hypothalamus
b.
Effectors
i. Glomerulus
=
GFR
ii. Hypothalamus
=
Thirst
Fig 20-18 on back of
iii. Heart
=
C.O. (cardiac output)
page/overview of system
iv. Vasculature
=
P.R. (peripheral resistance)
physiology for dehydration
v. DCT
=
Na Reabsorption
compensation
vi. Collecting Duct
=
Water Reabsorption
c.
Rules
i. Body responds to changes in osmolarity before it responds to changes in blood volume/pressure
ii. If two efferent pathways have opposite effects on the same effector, assume that negative feedback is
dominant; that is, the one that opposes the initial stimulus
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VIII. URINE CONCENTRATION IS DETERMINED IN THE LOOP OF HENLE AND COLLETING DUCTS
a.
b.
Osmolarity (urine concentration) is a measure of how much water is excreted by the kidneys
↑ (excess) water  kidneys excrete copious amounts of dilute urine with osmolarity as low as 50 mOsM
i. Removal of excess water in urine is known as dieresis
c. ↓ (low) water  kidneys conserve water and urine becomes highly concentrated, as high as 1200 mOsM
[1200 mOsM is four times as concentrated as blood which is 300
mOsM]
+
d. Kidneys alter urine concentration by varying the amount of 1) water and 2) Na reabsorbed in distal
nephron ((specifically the DCT))
↑ Osmolarity  excess
i. Produce Dilute Urine: Non-permeable water membrane (no H2O reabsorption) that allows solute
electrolyte solutes such as Na, K,
to pass
Cl, phosphates
ii. Produce Concentrated Urine: Nephron reabsorbs H2O while leaving solute in tubule lumen
↓ Osmolarity  decrease of
e. Osmosis (diffusion of water from ↓ to ↑ areas) will not take place unless concentration gradient exists
electrolyte solutes
i. Renal medulla maintains high osmotic concentration in interstitial fluid
ii. High Medullary interstitial osmolarity allows urine to be concentrated
f. Fluid Movement through the Loop of Henle
i. Reabsorption in the proximal tubule is isomotic
Loop Diuretics
ii. Filtrate entering loop of Henle (descending tubule) has osmolarity of 300 mOsM (isomotic to
1)
Furosemide (Lasix)
2)
Bumetanide (Bumex)
blood)
a.
Both work on loop of iii. Filtrate leaving loop of Henle (ascending tubule) has osmolarity of 100 mOsM (hyposmotic to
Henle
blood)
b.
Block Na-K-Cl (sodium
1. Hyposmotic fluid created by thick portion of ascending limb where Na2+, K+, and Cl- are
potassium chloride
pumps)
transported out of the tubule lumen
c.
Block reabsorption of
2.
These cells apical surface is impermeable to water thus when cells transport solute out
sodium (which thus
of lumen water cannot follow, creating a hyposmotic solution
blocks H2O
reabsorption to
iv. Hyposmotic fluid leaving the loop of Henle then passing through the distal tubule and into the
peritubular
collecting duct, its final concentration is determined by the epithelia cells permeability to water in
capillaries/interstitial
the distal nephron
tissue and space)
1. Cells not water permeable  water remains in tubule and filtrate remains dilute
d.
Used to lower fluid
volumes (increase
2. Cells water permeable  water diffuses out of tubule and into the interstitial fluid
excretion)
making filtrate becomes concentrated
e.
Given to patients with
v. Kidney’s homeostatic mechanisms can do nothing to restore lost fluid volume; one ingestion or
CHF, edema, high
blood volume, heart
infusion of water (through IV) can replace water that has been lost
failure
Loop of Henle
Volume
Concentration
Descending Loop
Ascending Loop
Decreases
Unchanged
Increases
Decreases
CAPTION: REFERENCE
7
CAPTION: OSMOLARITY CHANGES AS FILTRATE FLOWS THROUGH THE NEPHRON
g.
The Loop of Henle Is a Countercurrent Multiplier
i. The Renal Countercurrent Multiplier
1. Transfers solutes instead of heat as in a typical countercurrent exchange system
2. Filtrate enters descending limb which is permeable to water and impermeable to ions
a. Decreasing Volume
b. Increasing Concentration
i. Water moving by osmosis into more highly concentrated (bigger
gradient) of interstitial fluid of vasa recta
3. Ascending Loop of Henle
a. Impermeable to water
b. Permeable to ions (Na, K, and Cl)
i. Loss of solute (ions) causes filtrate osmolarity to decrease
c. 25% of Na and K reabsorption takes place in ascending limb
+
d. NKCC symporter (Na/K/Cl/Cl) uses energy stored in Na concentration gradient
+ +
to transport Na , K , and 2Cl from lumen of Henle into interstitial fluid
i. NKCC symporter inhibited by loop diuretic drugs (Lasix)
8
h.
i.
The Vasa Recta Removes Water
i. Water or solutes that leave the tubule move into the vasa recta if an osmotic or concentration
gradient exists between medullary interstitium and blood in vasa recta
ii. Blood flowing through the vasa recta removes the water reabsorbed from the loop of Henle
Urea Increases the Osmolarity of the Medullary Interstitium
IX. HORMONES OF THE FLUID/ELECTROLYTE BALANCE
Classification
Excrete/Retain Water/Salt
Blood Effects
Hormones Involved
Diuretic
Excrete Water
Atrial Natriuretic Peptide (ANP)
Anti-Diuretic
Retain Water
Natriuetic
Excrete Salt
Anti-Natriuetic
Retain Salt
↓ volume
↑osmolarity
Conserve volume
Maintain osmolarity
↓ volume
↓ osmolarity
Conserve volume
Maintain osmolarity
a.
Vasopressin (ADH)
Angiotensin II
Atrial Natriuretic Peptide
Angiotensin II
Aldosterone
Diuretics
i. Promote Excretion of or Water
ii. Cause decrease in blood volume
iii. Cause increase in osmolarity
iv. Hormone:
1. Atrial Natriuretic Peptide
a. Atrial Natriuretic Peptide (ANP; also known as atriopeptin)
b. Peptide hormone produced in specialized myocardial cells in the atria of the
heart
i. Related hormone [BNP] Brain Natriuretic Peptide is synthesized by
ventricular myocardial cells and certain brain neurons
c. Released by the heart when myocardial cells stretch more than normal [as
would occur with increased blood volume]
d. Enhance Na+ and H2O excretion
e. Inhibit the release of renin, aldosterone, and vasopressin
f. Effects of ANP
Inhibits (-) Aldosterone
Inhibits (-) Angiotensin
Inhibits (-) Vasopressin (ADH)
Promotes (+) GFR
2+
Decreases Na reabsorption
Prevents thirst and vasoconstriction
Decreases water reabsorption
Increases urine output
Caption: Actions of
Natriuretic Peptides
9
b.
Anti-Diuretics
i. Promote Retention of Water
ii. Conserve volume
iii. Main osmolarity
iv. Hormones:
1. Vasopressin (ADH)
a. When acting on target cells water pores are present in the apical membrane
that allow water to move out of the lumen (by osmosis) and into interstitial
fluid of the renal medulla
b. Posterior Pituitary hormone
c. Adds water pores (aquaporins) in the apical membrane of the collecting ducts
i. Aquaporins activated by arrival of ADH from posterior pituitary
gland and bind to designated cells, activating G-protein/cAMP
second messenger system
ii. Phosphorylation of intracellular proteins causes aquaporin-2 (AQP2)
vesicle to move to apical membrane and fuse with it, making the
wall permeable to water
iii. This process is imitated by Exocytosis and ended by endocytosis is
known as membrane recycling
10
d.
STIMULI ABBREVIATED
 Blood osmolarity ↑
 Blood volume ↓
 Blood pressure ↓
2.
Stimuli for Vasopressin secretion
i. Plasma Osmolarity
1. Monitored by Osmoreceptors, which are stretch sensitive
cells that active sensory neurons when osmolarity increase
above threshold
2. Osmoreceptors found in hypothalamus
3. When plasma osmolarity rises above 280 mOsM
Osmoreceptors fire [releasing vasopressin]
4. When plasma osmolarity is below 280 mOsM
Osmoreceptors do not fire [no release of vasopressin]
ii. Blood volume
1. Stretch sensitive receptors found in the Atria
2. When blood volume is low the receptors signal
hypothalamus to secrete vasopressin
iii. Blood pressure
1. Monitored by carotid and aortic baroreceptors
2. When blood pressure is low the receptors signal
hypothalamus to secrete vasopressin
Angiotensin II
a. (ANG II) signals aldosterone release from the adrenal cortex
b. Tropic hormone; stimulates aldosterone secretion in most situations
c. Most potent vasoconstrictor; constricts systemic arteries ↑BP without
changing blood volume
11
d.
e.
Stimulates
i. Thirst
ii. Aldosterone
iii. ADH
Is component of the RAAS [Renin-Angiotensin-Aldosterone System]
i. A multistep pathway for maintain blood pressure
1. RAAS stimulated by ↓ BP and Blood Volume
2. Juxtaglomerular Granular cells in afferent arterioles of
nephron secrete enzyme called renin
3. Renin activates angiotensinogen into angiotensin I
4. Angiotensin I encounters enzyme angiotensin converting
enzyme (ACE) and converts ANG I  ANG II
CAPTION: This map outline the control of aldosterone secretion as well as the blood pressure raising effects of ANG II
f.
Inhibited by pharmacological drug called ACE Inhibitors
i. Antihypertensive drug
ii. Drug blocks ACE-mediated conversion of ANG I  ANG II; thereby
helping to relax blood vessels and lower blood pressure
+
iii. Less ANG II  less aldosterone  decrease in Na reabsorption 
decrease ECF volume
12
c.
Natriuetic
+
i. Cause Na (sodium) loss/excretion
ii. Cause H2O loss/excretion
iii. Used to lower blood pressure and blood volume
iv. Hormone:
1. Atrial Natriuretic Peptide (ANP; also known as atriopeptin)
2. Peptide hormone produced in specialized myocardial cells in the atria of the heart
a. Related hormone [BNP] Brain Natriuretic Peptide is synthesized by ventricular
myocardial cells and certain brain neurons
3. Released by the heart when myocardial cells stretch more than normal [as would occur
with increased blood volume]
4. Enhance Na+ and H2O excretion
5. Inhibit the release of renin, aldosterone, and vasopressin
6. Effects of ANP
2+
Inhibits (-) Aldosterone
Decreases Na reabsorption
Inhibits (-) Angiotensin
Prevents thirst and vasoconstriction
Inhibits (-) Vasopressin (ADH)
Decreases water reabsorption
Promotes (+) GFR
Increases urine output
d.
Anti-Natriuetic
i. Promotes Retention of salt
ii. Conserves volume
iii. Maintains osmolarity
iv. Hormones:
1. Angiotensin II
2. Aldosterone
a. Steroid hormone synthesized in the adrenal cortex
+ +
b. Increases activity of Na -K -ATPase
+
+
c. Causes Na reabsorption and K secretion
d. Maintains blood volume
e. Stimulated by
i. Low osmolarity
ii. Low blood volume
13
f.
iii. Hyponatremia (↓ Na2+)
iv. Hyperkalemia (↑K)
v. Angiotensin II
Inhibited by
i. High osmolarity
CAPTION: Aldosterone action in principal cells
LOW BLOOD VOLUME/PRESSURE AND WATER CONSERVATION
a.
b.
Low Blood volume activates RAAS
Low blood volume stimulates vasopressin (ADH) secretion
HIGH BLOOD VOLUME/PRESSURE AND WATER EXCRETION
a.
b.
X.
Atrial baroreceptors respond to high pressure by releasing ANP
Pharmacological intervention: ACE inhibitors
THE DCT REGULATES THE FINAL SODIUM CONTENT OF URINE
a.
Effects/mechanism of Na+ reabsorption
NOTE: Na reabsorption generally linked to K
i. Effect on Water
secretion [Na-K exchange]
1. Drives water reabsorption
ii. Effect on Potassium
NOTE: Na-K exchange can be blocked by
1. Drives potassium reabsorption and secretion
aldosterone antagonist Amiloride
iii. Is enhanced by aldosterone
1. Aldosterone = Function in Na reabsorption/K secretion [released by adrenal cortex]
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b.
Diuretics
Diuretics
K Depleting (strong)
Loop Diuretics [Na-K-2Cl in ascending limb]
Thiazide Diuretics [TSCL in DCT]
K Sparing (weak)
Amiloride [ENaC in DCT]
ARB [Aldosterone Receptor Blocker]
ACE inhibitor
Thizaides

Act on ascending loop of Henle (DCT)

Block Na reabsorption  blocking water reabsorption  increasing urine dilution

Block K reabsorption  excrete excessive amounts of potassium

Giving to people with C.H.F, high BP, edema
XI.
Acid-Base Balance (pH Homeostasis)
a.
b.
c.
d.
e.
f.
Normal pH of body is 7.40 (slightly alkaline)
Normal pH range of plasma is 7.38-7.42
i. Acidosis
1. pH is to low
2. Neurons become less excitable and CNS depression results
ii. Alkalosis
1. pH is to high
2. Neurons become hyperexcitable firing action potentials at the slightest signal
Disturbances of acid-base balance are associated with disturbances in K+ balance
Potassium (K+) and (H+) exchangers
Compensation of pH leads to K+ imbalances
Loop of Henle
i. Proximal Tubule
1. Secretes Hydrogen
2. Reabsorbs HCO3ii. Distal Nephron
1. Controls Acid excretion
2. Intercalated cells (I cells) responsible for acid-base regulation
15