Renal Physiology

Unit 1
Chapter 25: Body Fluid
Total body water
Compartments
The sum of all fluid found in the body (42 liters or
60% of body weight)
Variations due to body size, gender, age, obesity
Extracellular fluid compartment
Plasma (3 L) not including blood cells
Interstitial Fluid (11 L)
Intracellular Fluid (28 L)
Transcellular Fluid
Includes synovial, peritoneal, pericardial, CSF,
intraocular fluid (1 L)
Water Intake and Output

To maintain homeostasis, water intake must

balance water output:
Sources of Water

Ingestion (about 2100 ml/day)

Absorbed from the GI tract (mainly the large intestine)
into the plasma compartment
Synthesis
Oxidation of carbohydrates (200 ml/day)
Contributes to intracellular fluid
Water intake and output

Water loss
Insensible water loss
Evaporation through ventilation and through the skin
(700 ml/day)
Does NOT include sweat
Sensible water loss
Sweat depends on ambient temperature and physical
activity (normally ~ 100 ml/day; can increase to 1-2 L per
hour with heavy sweating)
Feces = ~ 100 ml/day, increases with diarrhea
Kidneys (excretion of urine) = ~1400 ml/day
Composition of Plasma and
Interstitial
Plasma and Fluid
interstitial fluid is similar
Capillary wall is highly permeable to
water and ions, but not very
permeable to proteins
The protein concentration of plasma

is higher than interstitial fluid

(albumin, lipoproteins, antibodies
etc.)
Composition of Intracellular
Fluid
fig 25-2plasma
The (cell) membrane is not
permeable most ions and protein, therefore
there are many differences between ECF and
ICF.
ECF higher in Na+, Cl-, HCO3-
ICF higher in K+, PO4-3, Mg+2, organic
anions, protein
Definitions

Osmosis diffusion of water across a selectively

permeable membrane from a region of high
[H20] to a region of low [H20]
Moles vs. Osmoles
mole = 6.022 x 1023 particles of solute
Osmole = a mole of osmotically active particles of
solute
Example one mole of NaCl = 2 osmoles of osmotically
active particles.
Osmolality vs osmolarity
Osmolality = # moles / kg water
Osmolarity = # moles / L of water
Definitions

Osmotic pressure = amount of pressure

needed to oppose osmosis
Osmotic pressure () is related to
osmolarity:
= CRT (vant Hoffs law)

C = concentration of solutes (Osm/L)

R = ideal gas constant

T = temperature (K)
Isotonic/Hypotonic/Hypertonic
Solutions
(Isosmotic/hypo-
The osmolarity of ICF
osmotic/hyperosmotic)
is approximately 282
mOsm/L
Therefore, if a cell is
placed in pure water;
there would be an
osmotic pressure of
5400 mm Hg.
Plasma Osmolarity
Plasma sodium concentration is a good indicator
of plasma osmolarity.
Hyponatremia

Hypo-osmotic dehydration (Na+ loss)

Diarrhea or vomiting

Diuretic overuse

Decreased aldosterone (Addisons

disease)
Hypo-osmotic overhydration (H 2O gain)

Increased ADH secretion

Continued.
Hypernatremia
Hyperosmotic dehydration (H 2O loss)

Decreased ADH (diabetes insipidis)

Increased sweating (> water intake)

Hyperosmotic overhydration (Na+ gain)

Increased aldosterone
Urinary System Anatomy

Kidney external anatomy

Lie retroperitoneally on the posterior abdominal
wall
They lie between the T12 L3 vertebrae; the right
kidney is typically 1-2 cm inferior to the left one.
The hilum on the medial concave surface of the
kidneys serve as and entrance/exit point for:
Renal artery
Renal vein
Ureter
Renal nerve plexus (mainly SNS)
Urinary System Anatomy
Kidney Internal
Anatomy
Renal pelvis
Major and minor calyces
Renal medulla
Renal pyramids
Papilla
Renal cortex
Kidney Microanatomy

Nephron
There are approximately 1 million nephrons/per
kidney
Bowmans capsule
Proximal convoluted tubule
Loop of Henle
Short in cortical nephrons, long in juxtamedullary
nephrons
Distal convoluted tubule
Collecting tubule/duct
Renal Blood Supply

Renal artery segmental arteries

interlobar arteries arcuate arteries
interlobular arteries afferent arteriole
glomerulus efferent arteriole peritubular
capillaries / vasa recta interlobular veins
arcuate veins interlobar veins
segmental veins renal vein
Kidney Functions
Acid base balance
Electrolyte balance
Elimination of metabolic waste
Elimination of hormones and drugs
Role in gluconeogenesis
Endocrine function (renin)
Vitamin D activation
Blood pressure regulation / water balance
Nephron function
Excretion = filtration + secretion - reabsorption
Glomerular Filtration Rate

GFR = Kf X Net filtration pressure

GFR = glomerular filtration rate

Kf = glomerular capillary filtration coefficient
(product of surface area and permeability)
Net filtration pressure sum of Starlings forces.
Glomerular Filtration Rate

GFR = Kf x (PG PB G + B)

PG = Glomerular hydrostatic pressure

PB = Bowmans capsule hydrostatic pressure
G = Glomerular colloid osmotic pressure
B = Bowmans capsule colloid osmotic
pressure (normally = 0)
Regulation of GFR

Kf not used for regulation, but diseases can

effect Kf
Diabetes
Chronic hypertension
Kidney diseases generally decrease Kf
PB also not used for regulation, but
diseases can effect PB
Urinary tract obstruction
Regulation of GFR

B in a healthy state equals zero,

however disease can alter B
Proteinurea / albuminurea
Regulation of GFR

G changes during filtration:

Plasma protein concentration
increases as blood passes
from the afferent to efferent
arteriole
Regulation of GFR

The primary means by which GFR is regulated

is by changing PG.
PG increases GFR
PG decreases GFR

Glomerular hydrostatic pressure is determined

by:
Arterial pressure
Afferent arteriolar resistance
Efferent arteriolar resistance
Regulation of GFR

arterial pressure - GFR

Keep in mind that autoregulation keeps a fairly
even glomerular pressure
Afferent arteriole resistance (constriction)
GFR
Moderate Efferent arteriole resistance
(constriction) GFR
Large Efferent arteriole resistance
(constriction) GFR (biphasic response)
Regulation of GFR
Sympathetic effect on GFR
Causes vasocontriction of renal

arterioles and decreases renal

blood flow, thereby decreasing GFR
Effects are very minimal at normal

levels of sympathetic tone, but

during acute severe increases in
sympathetic activity, GFR can
decrease significantly.
Regulation of GFR

Hormones
Norepinephrine and epinephrine (from adrenal
medulla) constrict renal arterioles causing
decreased GFR and renal blood flow. As with the
SNS, only in acute severe conditions is there much
affect.
Endothelin is a vasoactive peptide released
when there is damaged vessels, and causes
vasoconstriction. It may contribute to kidney failure
in disease states where endothelin is secreted.
Regulation of GFR

Angiotensin II constricts efferent arterioles

Is a circulating hormone
Also is secreted locally by the kidneys (autocoid)
Angiotensin II is generally produced when there is
reduced blood pressure, or decreased blood
volume.
Constricting efferent arterioles increases
glomerular pressure, maintaining kidney function.
It also slows blood flow in the peritubular
capillaries which increases reabsorption of Na and
water.
Regulation of GFR

Endothelial derived relaxing factor (NO)

Autocoid that decreases renal vascular
resistance.
It is secreted tonically to help maintain normal
level of vasodilation.
Autoregulation of Renal Blood flow
and GFR
Purpose of regulating renal blood flow is to
maintain a relatively normal GFR, even when
systemic blood pressure changes.
Normal GFR occurs in MAP ranges from 75
160 mm Hg. (fig 26-16)
Tubuloglomerular Feedback

Juxtaglomerular complex (apparatus): This

feedback mechanism uses special cells in the
distal tubule and the afferent and efferent
arterioles :
Distal tubule macula densa senses NaCl
concentration
Afferent and efferent arterioles juxtaglomerular
cells

(figure 26-17)
Chapter 27: Tubular
Processing
Principles of tubular reabsorption (fig 27-1):
Two pathways through tubular epithelium
Transcellular (carrier mediated)
Pericellular (tight junctions)
Transport mechanisms
Active transport
Secondary active transport
Passive transport
Osmosis
Bulk flow
Tubular Tubular Processing

Primary active transport

Sodium potassium ATPase
Located on the basolateral membranes of tubular
epithelial cells
Creates a Na gradient (low intracellular sodium)
Creates a negative membrane potential
Passive transport of sodium
Therefore, Na diffuses passively either transcellularly, or
pericellularly due to the above gradients.
See fig 27-2
Tubular Processing

Other primary active transport carriers

Hydrogen ATPase
Hydrogen-potassium ATPase
Calcium ATPase
Tubular Processing

Secondary active transport

Na gradient caused by the Na/K ATPase drives
coupled transport (Na with another solute)
Na/Glucose carrier
Na/amino acid carriers
See fig 27-3 (top)
Tubular Processing

Secondary active secretion

Is the secondary active transport of a substance
in the opposite direction (antiport)
H+ can be secreted using this mechanism
See fig 27-3 (bottom)
Tubular Processing

Osmosis
The only mechanism that causes reabsorption of
water is osmosis
Osmotic gradient is created principally by the
primary and secondary active reabsorption of
solutes such as Na.
Water moves by osmosis either transcellularly or
pericellularly (assuming that part of the nephron is
permeable to water)
Solvent drag rapid H2O reabsorption brings
other solutes with it.
Tubular Processing

Bulk flow
Also known as ultrafiltration
Governed by hydrostatic and colloid osmotic
pressures.
Tubular Processing

Other passive reabsorption

Due to the active reabsorption of Na,

and the subsequent osmosis of water,

other solutes become concentrated in
the tubule lumen
Therefore, these solutes are

reabsorbed.
Examples: urea and Cl-
Tubular Processing
Summary of processing of selected
substances
Substance Filt reab ex
Glucose 180 g/day 180 0
Bicarbonate 4320 mEq/day 4318 2
Sodium 25560 mEq/day 25410 150
Chloride 19440 mEq/day 19260 180
Potassium 756 mEq/day 664 92
Urea 46.8 g/day 23.4 23.4
Creatinine 1.8 g/day 0 1.8
Tubular Processing

Transport maximum
For some substances, there is a maximum rate by
which they can be reabsorbed
Due to saturation of transport carriers with
excessive tubular (filtered) loads
Result is abnormally increased excretion of that
substance
Example glucose reabsorption in uncontrolled
diabetes mellitus
Proximal Convoluted Tubule

Histology
Cells have a lot of mitochondria
Brush border on apical (luminal) side
Basal channels (on basolateral side)
Early Proximal Tubule

Na/K+ pump
2 cotransport:
Na / glucose symport (100% reabsorption)
Na / amino acids symport (100% reabsorption)
Na / H+ antiport (H+ secretion)
HCO3- absorption (mechanism chapter 30)
Aquaporin I water reabsorption via osmosis
Late Proximal Tubule

Continued Na/K pump

Passive transport Cl-
Active secretion of organic acids and bases
(i.e. bile salts, oxalate, urate,
catacholamines)
Active secretion of drugs and toxins
Proximal Tubule

By the time the filtrate reaches the end of the

Proximal tubule, 65% of H20, Na, Cl, K are
reabsorbed, and all the glucose and a.a.
The proximal tubule is isosmotic
Loop of Henle

Histology
Thin descending limb
Thin ascending limb
Thick ascending limb
Loop of Henle

Thin descending limb

Very permeable to H20
Somewhat permeable to solutes
No active reabsorption
Thin ascending limb
Impermeable to H20
Loop of Henle

Thick ascending limb

Also impermeable to H20
Na/K+ pump
Na+/H+ antiport (H+ secretion)
1-Na+, 2-Cl-, 1-K+ co-transporter (reabsorption of
these three ions)(target for loop diuretics)
Paracellular reabsorption of Mg++, Ca++, Na+,
and K+ (due to electrochemical gradient)
The thick limb is hypo-osmotic
Distal Convoluted Tubule

Early Distal tubule

Characteristic similar to thick

ascending loop of Henle

Contains a Na/Cl cotransporter

that is sensitive to thiazide

diuretics
Distal Convoluted Tubule

Late distal tubule (and cortical part of

collecting duct)
Principal Cells
Na/K+ pump
Sodium resorption (passive) sensitive to aldosterone
Potassium secretion (passive) sensitive to aldosterone
Sensitive to K+ sparing diuretics
With ADH is permeable to water (reabsorption)
Distal Convoluted Tubule
Late distal tubule (and cortical part of
collecting duct) continued:
Intercalated cells
Reabsorbs K
secretes H+ (H+ ATPase)
Secretes HCO3-
Medullary Collecting duct

Small amount of H20 and Na reabsorption

Passive reabsorption of Cl-
Also sensitive to ADH
Is permeable to urea (some reabsorption)
Also has an H+ ATPase (secretion)
Glomerulotubular Balance

This refers to the balance between GFR and

reabsorption; as GFR goes up, so does
reabsorption.
This is the second line of defense against large
changes in GFR
Recall the first line of defense was
glomerulotubular feedback aka renal
autoregulation.
Governed by hydrostatic and colloid osmotic
forces of the IF and peritubular capillaries.
Hormones and control of
Reabsorption
Aldosterone
Secreted by zona glomerulosa cells of the adrenal
cortex
Promotes Na reabsorption and K secretion
Target principle cells of the cortical collecting
tubules
Mechanism
Stimulates Na/K pump on basolateral membrane
Increases Na permeability of luminal membrane
Hormones and Control of
Reabsorption
Angiotensin II
Secreted by liver as angiotensinogen; converted
by renin into angiotensin I, then to Angiotensin II
by ACE in the lungs.
Effects:
Increases aldosterone secretion
Constricts efferent arterioles; decreasing Pc of
peritubular capillaries and increases reabsorption
Stim Na/K pump, and Na/H exchanger, therefore a lot of
Na is reabsorbed.
Hormones and Control of
Reabsorption
ADH
Secreted by posterior pituitary gland
Increases water permeability of distal tubules
Mechanism causes insertion of aquaporin-2 into
tubular membrane.
Atrial Natriuretic Peptide
Secreted by distended atria
Decreases Na and water reabsorption
PTH
Increases reabsorption of Ca in the distal tubules
Measurement of Renal
Clearance
Definition of Clearance:
The volume of plasma that is completely cleared
of a substance by the kidneys per minute

This is a theoretical value, as it is impossible to

completely clear a substance from a given volume
of plasma.
Measurement of Renal
Clearance
Consider the following:
let Cs = clearance rate of substance (ml/min)
and
Let Ps = plasma [s] (mg/ml)

Therefore Cs x Ps = the amount of substance that

moves from the plasma into the tubules (mg/min)
Measurement of Renal
Clearance
Also consider:
Let V = urine flow rate (ml/min)
and
Let Us = urine [s] (mg/ml)

Therefore Us X V = rate of movement of

substance from the tube into the urine, or the
excretion rate (mg/min)
Measurement of Renal
Clearance
IF a substance is freely filtered, but not
reabsorbed or secreted, then:
C s x P s = Us x V
Which is saying that the mg/min of clearance of a
substance from the plasma into the tubules is the
same as the mg/min of the substance showing up
in the urine (excretion).
Rearranging the equation, we can measure the
renal clearance (Cs)
C s = Us x V / P s
Measurement of Renal
Clearance
Since Cs is essentially the same as GFR, the
equation can be re-written as:
GFR = Us x V / Ps

Inulin can be used to measure GFR

See figure 27-17
Measurement of Renal
Clearance
Creatinine can also be used:
It is produced by the body, so it doesnt need to be
injected
drawback: it is secreted in small amounts in the
kidney tubules
correction: measurement of Pcreatinine overestimates
its concentration by about the amount it is
secreted, so creatinine is still a good indicator of
GFR.
Measurement of Renal
Clearance
One can compare inulin clearance with other
substances.
If the clearance of a substance is equal to inulin,
then the substance is filtered, but not reabsorbed
or secreted
If the clearance of a substance is less than inulin,
then the substance is reabsorbed
If the clearance of a substance is greater than
inulin, then the substance is secreted.
Often expressed as a clearance ratio C s / Cinulin