Renal Review

Ana Ivkovic and Rahul Dave

Kidney functions

Primary: water regulation and electrolyte

balance--homeostasis
The renal system functions to maintain the
intravascular volume (of body fluids)
Other:
Endocrine: renin, erythropoieten, calcitriol
Liver-like fxns: glucose synthesis
Basic Concepts

Excretion = Filtration - Reabsorption +

Secretion

Filtration: Bowman’s capsule

Reabsorption: Peritubular capillaries
Secretion: Peritubular capillaries
Measuring Fluid Compartments

Total Body Water = 60% total body weight

2/3 = ICF 1/3 = ECF

1/4 = Plasma 3/4 = Interstitial Fluid

Total Body Water: varies with fat

20-40-60 Rule
ICF high in K and Mg; ECF high in Na, Cl
Plasma high in protein; interstitial fluid low in
protein-- Gibbs Donnan (neg. charged prots attract
more pos. charge)
Smallest compartment (plasma) most important
(intravascular volume that is controlled by kidney)
Osmolarity and Oncotic Pressure
Normal plasma osmolarity = 285-290 mOsm/L
Tightly controlled
Osmolarity vs. Osmolality
Osmolarity = mmol solute/L solution
Osmolality = mmol solute/kg h2O
Reflection coefficient:
0 = ineffective osmolyte (urea, ethanol--freely permeable)
1 = effective osmolyte (Na, K, glucose w/o insulin; “draw” water)
Oncotic Pressure: the fraction of plasma osmolarity
that is due to plasma proteins
Tonicity vs. Osmolarity
Osmolarity
Describes the osmotic properties of a solution
Tonicity
Refers to the osmotic effect on the volume of a cell
Ex: hypotonic soln--water moves in, cell swell
Isosmotic solns not necessarily isotonic (has
to do w/ concept of reflection coefficient--ex
of urea solution and RBC)
Darrow-Yanet Diagrams--Think
Logically!
All volume disturbances originate in the ECF
compartment
Changes in the ICF compartment are in
response to changes in the ECF
“hyposmotic contraction” refers to the
volume of fluid that remains
Volume contractions
Diarrhea, vomiting, loss of blood--isosmotic
volume contraction
Diaphoresis (sweating), dehydration--
hyperosmotic contraction
Remember that sweat is hyposmotic
Addison’s disease (lack of aldosterone)--
hyposmotic volume contraction
Volume expansions (rarer)
Isotonic volume expansion (isotonic saline
IV): ECF expands, ICF doesn’t change
Hypertonic volume expansion: ECF
osmolarity increases, draws fluid from ICF
Hypotonic volume expansion: ECF
osmolarity decreases, adds fluid to ICF
(examples: psychogenic polydipsia, SIADH)
Renal vascularization
Renal artery -->
interlobar artery -->
arcuate artery -->
interlobular artery-->
afferent arteriole* -->
glomerular capillaries--
> efferent arteriole* -->
peritubular capillaries
*serial arrangement of
arterioles--important!
Juxtamedullary vs. Superficial Nephron

JMN has long Loop of Henle

Generates a concentrated urine
JMNs are what we lose with age
Renal Clearance and Blood Flow

C.O. = 5.2 L/min

RBF = 1.2 L/min (20% of cardiac output)
RPF = .66 L/min (plasma = 55% of blood); also
equal to the clearance of PAH (filtered and
secreted)
GFR = Clearance of inulin or creatinine
Inulin is filtered but not secreted or reabsorbed
Creatinine clearance a slight overestimate of GFR
because it is partly secreted (GFR = 0.9 X
Ccreatinine)
Filtration Fraction = GFR/RPF, normally 20%
PAH
Used to measure RPF
Effective RPF = ([U]PAH x V) / [P]PAH = CPAH
Clearance Ratio
CR = Cx/Cin
If CR = 1, substance “x” is only being filtered
If CR < 1, substance “x” is being reabsorbed
If CR > 1, substance “x” is being secreted
GFR:
1. Is dependent on hydrostatic pressure inside
glomerular capillaries
2. Depends on the oncotic pressure inside glomerular
capillaries
3. Is equal to the clearance of inulin
4. Under normal conditions, is rarely dependent on the
oncotic pressure inside Bowman’s space
5. Creatinine is used to calculate it
6. Three of the above
7. All of the above
Starling’s Forces of capillary exchange
GFR = Kf (PGC - PBS - ∏GC)
Hypoalbuminemia increases GFR
PBS: low unless obstruction present (kidney
stones increase GFR)
Basement membrane has fixed negative
charge--> neg. charged prots can’t get
across --> oncotic pressure in Bowman’s
space = 0
Cont’d
Hydrostatic Pressure is high and relatively constant
(due to serial arterioles)
Oncotic Pressure increases along length of
glomerular capillary (as more fluid is filtered out)
Filtration occurs upstream while reabsorption
occurs downstream
Q: why does a low GFR result in increased
reabsorption?
A: more time to filter --> oncotic pressure increases
AFFERENT AND EFFERENT ARTERIOLES ARE
THE
MAJOR SITES OF REGULATED RESISTANCE IN
THE
RENAL VASCULATURE:

Glomerular capillary is unique: 2 sites of

Autoregulation
Myogenic Mechanism (Bayless): intrinsic reflex
mechanism of smooth muscle; increased pressure
causes vasoconstriction
Tubuloglomerular feedback: macula densa
senses increased filtered load of NaCl--> sends
signals to afferent arteriole to vasoconstrict, thereby
decreasing the filtered load (by decreasing GFR
back to normal)
Both processes serve to keep RBF and GFR
constant
Sympathetic Innervation
There is no parasympathetic input to the kidneys
Sympathetic innervation of the afferent and efferent
arterioles is the major regulator of RBF and GFR
Vasoactive compounds also act on afferent and
efferent arterioles: NE, Angiotensin II, Endothelin-->
constrict; Ach, NO, PGs, etc --> dilate
Low vs. severe sympathetic drive--examples of
exercise and hemorrhage
Urine formation
Ultrafiltration of plasma
Reabsorption of H2O and solutes from tubular fluid
Active and passive processes
Transcellular and paracellular (lateral space)
transport; latter occurs in proximal tubule due to
leaky tight junctions--> ions pass, followed by H2O
In collecting duct tight jxns are very tight and do not
allow passage of water, proteins, or solutes
Solute Regulation in
Nephron Segments
Reabsorption and Secretion along
Proximal Tubule
Isosmotic fluid
reabsorption
Reabsorbs 2/3 of
filtered load of Na and
water (Aquaporin 1)
Highly permeable to
H2O; solvent drag of K
and Ca
Understand TF/P
graph
Upper Segment of PT
Na cotransported along with bicarb, glc, amino
acids, phosphate (luminal membrane)
H+ secreted as counter-transport with Na (luminal
membrane)
Sodium bicarbonate is reabsorbed (basolateral
membrane)
Under normal conditions, reabsorption will increase
as plasma [gluc] increases
Once plasma [gluc] reaches a certain level, all
glucose carriers in the PT will be saturated, leaving
some glucose behind
Tm of SGLT-2 (sodium coupled) is 200g/dl, which
Lower Segment of PT
NaCl reabsorbed transcellularly (1/3) and
paracellularly (2/3); due to transepithelial
voltage
Amino Acids and Bicarbonate have been
completely reabsorbed
Glucose SGLT-1 (2 Sodium coupled)
transporters move glucose against higher
gradient
Thick Ascending Limb
Reabsorbs 1/4 of filtered Na
Has the Na-K-2Cl cotransporter
Inhibited by Furosemide (loop diuretic)
Impermeable to water; tubular osmolarity
decreases (“diluting segment”)--> separation
of movement of water and solute
Lumen becomes positively charged, causing
paracellular transport of Na, K, Ca, and Mg
Early Distal Tubule/Collecting Duct
Also impermeable to water (like TAL)
Continues the dilution of urine; the “cortical
diluting segment”
Reabsorption of Na/Cl (cotransporter)
Inhibited by Thiazide diuretics
Thiazide diuretics unique in that they increase Ca++
reabsorption (Loop diuretics increase Ca++ excretion by
diminishing NaK2Cl + lumen effect)
Late Distal Tubule/Collecting Duct: fine
tuning
Principal cells--reabsorb Na, H2O, and secrete K+
Impermeable to water, except in presence of ADH (Vasopressin)
ADH causes water channels to relocate to apical cell membrane
(AQUAPORIN 2)
Na (transcellularly) and Cl (paracellularly) are reabsorbed
Aldosterone causes an increase in Na absorption and increases K
secretion
Spironolactone (K-sparing) blocks aldosterone; other K-sparing
diuretics (Triamterene, Amiloride) act directly on the Na channel,
independent of aldosterone
Intercalated cells--secrete H+ through primary active transport
exchange H+ out of cell for K+ into cell; K+ reabsorption
possess carbonic anhydrase activity for bicarb reabsorption
Miscellaneous Renal Stuff
Na+, Ca++ are never “secreted”; rather, fail to
reabsorb
Prostaglandins released during hypovolemic shock
to increase RPF and prevent renal ischemia
Aldosterone: promotes Na reabsorption and K
secretion (via action on principal cells); also
promotes H+ secretion (via action on intercalated
cells)-->a link between volume and acid-base
regulation
Posm = 2[Na] + 2[Glucose] + [BUN]
ADH: OSMOREGULATION
Genetic Defects that Target Tenal
Transport Mechanisms
Bartter’s Syndrome: defect in NaK2Cl
transporter
Gettelman’s Syndrome: defect in Na/Cl
cotransporter
Liddel’s: defect in ENaC (turned on)
Pseudohypoaldosteronism: defect in ENaC
(turned off--> Na doesn’t get reabsorbed-->
volume contraction
Graphs to be familiar with:
WATER BALANCE
Urine flow rate is never zero
There is an inverse relationship
between urine flow and osmolarity
Normal urine osmolarity ≈ 600 mOsm/L
Range = 50 - 1200!! (kidneys can concentrate urine
up to 4x the plasma concentration)
Control Mechanisms of Osmoregulation
Osmoreceptors
Increase in plasma osm--> hypothalamus stimulated to release
ADH (hypothalamic set point ≈ 285 mOsm/L solution)
Respond to < 2% change in plasma osmolarity
Most important control in osmoregulation
Baroreceptors
Respond to changes in Blood Pressure
Require a 15-20% change in BP before activation
Disorders of Osmoregulation
Psychogenic Polydipsia,
Hypothalamic/Central Diabetes
Insipidus: low ADH
Nephrogenic Diabetes Insipidus:
ineffective ADH (kidney unable to
respond to ADH)
Mechanisms to Concentrate Urine
Countercurrent Multiplication--creation of osmotic
gradient
Loop of Henle
Generates a urine that is concentrated as high as 600 mosm/L
Urea recycling
Medullary Collecting Duct
Needed to increase the osmolar gradient from 600 to 1200 mosm/L
Kidneys use urea to do osmotic work when in state of antidiuresis
Countercurrent exchange--vasa recta maintains the
medullary insterstitial osmotic gradient set up by the
countercurrent multiplier
Diuresis vs Antidiuresis
Understand the diagrams on p. 9
Water diuresis: most concentrated urine just
before ascending limb and TAL; most dilute
at end of CD
Antidiuresis: most concentrated in lumen at
level of renal papillae (in medulla); most
dilute at TAL
SODIUM
REGULATION
Renin, Angiotensin, Aldosterone
Renin secretion stimulated by:
Decrease in effective circulating volume (decreased pressure at
afferent arteriole)
Increase in sympathetic nerve activity
Tubuloglomerular feedback (decreased Na load sensed by macula
densa, causing renin release)
Angiotensin II:
Arteriolar constriction--> increases TPR
Increases Aldosterone
Increases ADH and thirst
Aldosterone causes:
Na reabsorption at principal cells
K secretion in CD
Aldosterone secretion:
Increased by ACTH, Angiotensin II, high
plasma [K+], cases of volume contraction
Decreased by *ANP* and high plasma Na+
(feedback inhibition)
ANP: OPPOSES RAAS; increases Na+ excretion during cases
of volume expansion (cardiac myocytes are stretched)

Note: Na+ alterations do not affect plasma osmolarity,

rather they affect the effective circulating volume; H2O
homeostasis and ADH determine plasma osmolarity
Aldosterone escape
A protective mechanism during cases of
abnormal aldosterone elevation (example of
adrenal tumor); system becomes insensitive to
aldosterone.
Renal Physiology

Lectures 41 to 48

Rahul Dave’ (rdave2@uic.

edu)
I can’t go through everything in detail.
Know the handout.

My goal is to make this make sense to you, and orient your

studying.

Pay attention to major vs minor factors.

Minor doesn’t mean less important to study, but helps you keep
changes in perspective

You need to memorize the regulation, etc … and understand

the logic. It’s easy to talk yourself into something wrong.
Potassium Balance
K+ distribution and homeostasis

Plasma K is low … must be controlled well

Determines membrane potential

Metabolic alkalosis causes hypokalemia

(and vice-versa)

Rules of thumb: understand mechanisms

Na and K go opposite
 K+ Transport
K+ Transport

See diagrams in handout for cellular transport

pathways in different sections
Regulation of K+
MAJOR FACTORS
K+ itself (K promotes its own secretion)
Aldosterone (Na+ excr., K+ reabs., H+ excr.)

MINOR FACTORS
Tubular flow increases secretion
ADH no net effect
Alkalosis (acute) increases secretion
Tubular Na+ increases secretion
Insulin Increase reabsorption
Epinephrine Decreases secretion (fight/flight)
Diuretics

See diagrams of cell transport pathways

Control of Circulating Volume
Small fraction of TBW … can’t detect it directly.
Also, since detection and changes are indirect,
the changes must occur slowly

Measured by BP (myogenic feedback) or [Na+]

(tubuloglomerular)

Controlled by changing Na+

Volume Sensors & Effectors
Baroreceptors … detect pressure
Central (Left atrium; carotid sinus)
ADH Na reabs; collecting duct permeability
Intrarenal volume sensors
Pressure: myogenic feedback
Na (also K & Cl, maybe): tubuloglomerular
Low ECF volume makes you thirsty
Sympathetic overdrive (fight/flight) –
conserve water & ↓ peripheral blood flow
Mechanisms Controlling ECF

Cardiac atria … secrete ANP … lowers GFR

Aortic Arch Baroreceptor … Sympathetic system

Macula Densa … Renin-Ang-Ald System

Hydrostatic/Oncotic pressure balance

Adrenal Cortex … hormones like aldosterone

+
All of these affect Na
Calcium and
Phosphate Balance
 2+
Rules of Thumb: Ca

Hitchhiking only takes you so far. But try to

understand why & how these are true.

In the PCT & TAL: Ca2+ follows Na+ paracellularly

In the DCT & CD: Ca2+ is regulated by PTH
 3-
Rules of Thumb: PO4
Try to understand why & how these are true.

In the nephron it undergoes paracellular transport

Controlled by PTH in the proximal tubule

PTH
Phosphate Trashing Hormone in urine
Absorb (P) from gut & bone to incr. plasma (P)
Excrete it in the urine

But Ca2+ and PO4 can’t be together

So if (P) is low, Ca2+ is high, and vice-

versa

PTH, not calcitonin, is a major controller

2+
of Ca .
Vitamin D Synthesis

This is a stupid detail, but winds up being

tested sometimes (No promises about
Hudson)
Vit D is synthesized in liver & Kidney
D (liver) 1-OH-D (kidney) 1,25-OH-D

You need Vitamin D to absorb Ca2+

Think: Vit-D fortified milk
Acid-Base: Basics
Removing Acid or Base

Buffers
Blood seconds
Intracellular minutes
Lung hours
“compensated state”
Kidneys days

Net acid excretion counts NH4, Titratable Acid, HCO3-

Titratable (weak) acids include lactic acid, ketone bodies, etc.
Strong acids are secreted as their Na salts (eg, Na2SO4)
Buffering Mechanisms

[HCO3-] = 24
pH = 6.1 + log ————————— = 7.4
0.03 x P-CO2 = 40

Know this and make sure you can

calculate it!
Lung Mechanisms

CO2 is an acid and gets blown out by

respiration.
So when you sprint, you develop lactic acidosis. This is
metabolic acidosis. To get rid of the acid, you hyperventilate
and breathe faster.
 Kidney Mechanisms

Mainly by HCO3-

H2O + CO2 CA H2CO3 HCO3- + H+

Kidney: HCO3-

Locations: look at cell diagrams

Regulation
Proximal tubule: follows Na+ (understand why)
Na/H antiport. Whenever one H+ exits, a tubular HCO3- is used
up to neutralize it. Also, to regenerate that H+, a HCO3 is made,
which is transported to the blood.
Systemic Acidosis (in PCT, Henle, CD)
 +
Kidney: H

H+ is usually tied to other ions

In the intercalated cell of collecting duct,

there is a ATP-dependent H+ pump that
secretes H+

Upregulated by aldosterone
Nitrogen Removal (NH3 or NH4+)

The mechanisms are complicated

Know that H+ acidifies & traps NH3 in the lumen

(as NH4+)
K+ also regulates NH4+ production … don’t worry

(The mechanisms are important if you want to

do really well)
Clinical Evaluation of
Acid-Base Disorders

the simple way …

Q1. Acidosis or Alkalosis?

Remember compensation is never 100%

pH < 7.4 …. Acidosis

pH > 7.4 …. Alkalosis

pH = 7.4 ….. You’re fine (or … mixed)

Metabolic or Respiratory

If it’s acidosis (or alkalosis) look for the

source of acid (or base)

HCO3 < 24 CO2 > 40

HCO3 > 24 CO2 < 40
metabolic respiratory
Compensated or Uncompensated?

Check with the formulas …

Fig 43.23 in Berne & Levy
I’m not sure whether he gave you these formulas. If he didn’t don’t worry.

Check the nomogram …

It will tell you acute vs chronic.
Is it Mixed?

Note that HCO3- and CO2 move in opposite

directions

If they move in the same direction … you have

a mixed disorder.
Clinical Causes …
Metabolic Acidosis: Diabetic ketoacidosis,
diarrhea
Metabolic Alkalosis: antacid, vomiting (will
loose Cl too)
Respiratory Acidosis: Hypoventiliation,
pulmonary edema
Respiratory Alkalosis: Hyperventilation
Cell Diagrams

You can find these in Costanzo, Hudson’s H/O or

Berne & Levy.

Best study tool: Draw these out yourself. Know

them cold.
Stone Kidneys are cool
….

Good luck