Renal Physiology-Review
William DiFilippo, MD
Assistant Professor of Medicine
Program Director, Nephrology Fellowship
SUNY Upstate Medical University
Objectives
Review normal renal physiology and
tubular function
 Understand hormonal effects on renal
function
 Comprehensive review of renal
pharmacology
 Clinical review of applications of diuretics
and medications targeted in the kidney
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Disclosure
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I have no disclosures
Functions of the Kidney
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Water, thus volume, regulation
Waste excretion: simply regulate what we
need (homeostasis and electro-neutrality)
and excrete what we don’t need-diet and
cell catabolism
Hormonal secretion: Renin, AII, Pg (E2, I),
Nitric Oxide, Endothelin, Bradykinin, EPO,Vit
D3 (1, 25 dihydroxy vit D)
Basic Processes: Reabsorption (removal of
substances from filtrate), Secretion (addition of
substances to filtrate)
Functions of the Kidney
Mechanisms of balance: Secretion and
Reabsorption
 Na+, Cl-, Water are reabsorbed
 H+ is secreted
 K+ and Uric Acid are both reabsorbed
and secreted
 CREATININE IS UNCHANGED-What is
filtered is what is in urine! (inulin is the
same)
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Components of the NephronGlomerulus
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Afferent Arteriole and Efferent
Arteriole
Glomerular Tuft
BP driven-autoregulation via AII and
Pg E2,I balance
Glomerular filtrate creates Filtration
Fraction
Filtrate enters Bowman’s space to
begin processing in the tubular
network
Juxtaglomerular Apparatus-located
near vascular pole-specialized cells
composed of Distal Tubule and
Afferent arteriole-regulates BP and
filtration rate at glomerulus
1-1.3 million glomeruli (cortex) in
each kidney
19 km (11.8 miles)-surface area
6,000 cm2
Filtration surface area 516.1 cm2
Components of the NephronProximal Tubule
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Early Segment: specific transport
systems for Transcellular
(reabsorption %)
HCO3- (85%)*
NaCl (66% Na)
Glucose (near 100%) **(NaGlucose Transporter)
Amino Acids (near 100%)
Other Organic Solutes
*Site of Action Carbonic Anhydrase
inhibitors
**site of action of SGLT2 drugs for
the treatment of diabetes
Potassium handling trough
Paracellular pathway (65%)
Water Reabsorption-Transcellular
(Aquaporin 1 channel) and
Paracellular-(total 60%)
Very permeable segment
Carbonic Anhydrase-enzyme that
converts H2CO3(carbonic acid)
into CO2 and Water
Components of the Nephron-Loop
of Henle
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Descending limb-PASSIVE
water movement with high
permeability (Aquaporin
1))
Water movement based on
concentration gradient in
medullary interstitium
*osmotic diuretics-enter
through proximal tubule
and oppose water
extraction thus
AQUARESIS
Thin Ascending Limbpermeability to small
solutes (NaCl-25% of
filtered Na),
IMPERMEABLE to watercreates dilute tubular fluid,
THUS THE DILUTING
SEGMENT
Components of the Nephron-Thick
Ascending Limb of Loop of Henle
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Active luminal Na+/K+/2Clcotransporter—This is the site
of action of Loop Diuretics
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Note:
Na+/K+/2Cl- is electro-neutral
Though it’s action creates a net
K+ within the cell as a result
of the ROMK channel, thus
restoration of electroneutrality
results in paracellular
reabsorption of Mg2+ and
Ca2+.
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Inhibiting NKCC2 with loop
diuretics reduces the lumen
+potential and creates increase
in loss of Magnesium and
Calcium in the urine along with
K,NaCl
ROMK
Components of the Nephron-Distal
Tubule
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Two parts: (about 10% filtered
NaCl reabsorbed)
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DCT1:
NaCl active co-transporter
{NCC}
Relatively impermeable to water
Magnesium channel: apical
Na/Mg transporter: basolateral
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DCT2:
NaCl active co-transporter
{NCC}
Na+ channel: apical [ENaC]
Ca++: apical
Cl- channel: basolateral
Ca/Na active cotransporter:
basolateral
Ca active transporter:
basolateral
Calcium active transporters
under the influence of
Parathyroid hormone
Components of the Nephron:
Collecting Tubule-Cortical
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The Final Pathway: Two Cell types
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Reabsorbs small amount (2-5%)
NaCl
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Principle Cells:
Na, K and water transport
Home to MRA and ENaC
channels
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Intercalated Cells: Acid-Base
function
Alpha: H+
Beta: HCO3Primary role of the collecting
duct is final modification of urine
concentration and composition,
as well as to help with
maintaining the medullary
interstitium concentration
gradient
Components of the Nephron:
Collecting duct water channelsmedullary
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AntiDiuretic
Hormone
(Vasopressin)
Aquaporin 2: water
reabsorption to
ADH-Apical (V2
receptors)-in the
absence of ADH the
collecting tubule is
impermeable to
water!
 Aquaporin 3-water
reabsorption and
glycerol permeabilitybasolateral
 Aquaporin 4-water
reabsorptionBasolateral
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THE NEPHRON
THE NEPHRON-REALLY!
Renal Autocoids:
Role in pharmacology of diuretics
Adenosine: creates decrease in renal blood flow
and glomerular filtration via A1 receptor found at
afferent arteriole and Proximal tubule (tubuloglomerular feedback)—Role to reduce work of
the nephron in hypoxic states (CHF, Shock,
Respiratory failure, etc)
 Prostaglandins: PgE2 role in vasodilatation of
afferent arteriole in autoregulation of glomerular
blood flow. Blunts Na reabsorption in LOH and
water transport in collecting tubules
 Peptides: ANP and BNP play a role in
vasodilatory response of glomerulus in heart
failure
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Pharmacologic Hormones and the
Kidney
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Renin-Angiotensin system: Role in treatment of
Hypertension-predominant function is vascular tone
of glomerulus
Erythropoietin: normally produced in interstitial
fibroblasts near proximal tubule. Role in the
treatment of Anemia
Aldosterone: Role in the treatment of
Hypertension. Na resabsorption in collecting duct
through activation of MR receptor
1,25 DihydroxyVitamin D3: proximal tubular cell
conversion of 25-OH from via 1-alpha hydroxylase
ADH: V2 receptors in medullary collecting duct.
Role in water reabsorption. Hyperosmolality
stimulates
Summary
The nephron is the responsible for:
1. Water regulation and homeostasis
2. Excretion of solutes as a direct result of
catabolism and diet
3. Hormonal function in the regulation of
hypertension, anemia, bone metabolism,
cellular function
4. Site of action of diuretic influence
function at specific segments
Summary
Glomerulus
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The glomerulus-specialized capillary loop
that is driven by systemic pressure to
present plasma filtrate to tubular network
for processing in the maintenance of internal
homeostasis
Ability to autoregulate between systemic
pressure of 80-200 mmHg under the
influence of angiotension II and Pg E2, I
Think of it as a filter permitting only passage
of plasma into tubular network
Summary
Tubular Network
Highly specified structural and functional
portions of the nephron
 Each plays a unique role in processing
ultrafiltrate
 Each has specialized sites and/or channels
that play a role (or appear to play a role)
in either treating or creating disease—
You will get more of this in Nephrology
Medicine
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Summary
See you all tomorrow for PART II-The DIURETICS