PHS101

RENAL PHYSIOLOGY 1 & 2 W3 T1 & 2

Dr. Memoracion February 3, 2018

Outline 5. Regulation of acid base balance

I. IMPORTANT HOMEOSTATIC FUNCTIONS  Normal pH is maintained by buffers within body fluids and by the coordinated
II. KIDNEY: FUNCTIONAL ANATOMY
action of the lungs, liver, and kidneys.
III. ULTRASTRUCTURE OF THE NEPHRON
IV. ULTRASTRUCTURE OF THE GLOMERULUS
V. ULTRASTRUCTURE OF THE JUXTAGLOMERULAR APPARATUS ‒ By excreting acids and by regulating the body fluid
VI. CLINICAL CORRELATION buffer stores. The kidneys are the only means of
VII. ASSESSMENT OF RENAL FUNCTION eliminating from the body certain types of acids,
A. RENNAL CLEARANCE
B. GLOMERULAR FILTRATION RATE such as sulfuric acid and phosphoric acid,
VIII. FACTORS AFFECTING FILTERABILITY OF MOLECULES generated by the metabolism of proteins
IX. DYNAMICS OF ULTRAFILTRATION
X. REGULATION OF RENAL BLOOD FLOW
XI. INTRINSIC REGULATION 6. Regulation of erythrocyte production
XII. EXTRINSIC REGULATION  One consequence of many kidney diseases is a reduction in erythropoietin
Lecture, Book: Berne and Levy – Box, Guyton, Keypoints – Broken box, production and secretion
Side notes from the transer  Erythropoietin stimulates red blood cell formation by bone marrow
RENAL PHYSIO 1: Functional Anatomy  Decreased erythrocyte production contributes to the anemia that occurs in
RENAL PHYSIO 2: Urine Formation chronic kidney disease (CKD)
o A progressive loss in kidney function over period of months or years

IMPORTANT HOMEOSTATIC FUNCTIONS

1. Excretion of metabolic waste product and foreign chemicals
 The kidneys elimnate the following substances from the body at a rate that
matches their production:
o Urea – from amino acids
o Uric acid – from nucleic acids
o Creatinine – from muscle creatine
o End products of hemoglobin metabolism
o Metabolites of hormones
‒ The kidneys also eliminate toxins/foreign
substances that are either produced by the body or
ingested, such as pesticides, drugs, and food
additives
2. Regulation of water and electrolyte balance
 The kidneys are essential in regulating the amount of several important
inorganic ions in the body including Na+, K+, Cl-, bicarbonate (HCO3-),
hydrogen (H+), Ca++, and inorganic phosphate (Pi)
o Excretion of these electrolytes must be equal to daily intake to
maintain appropriate total body balance
 If intake of electrolytes exceed its excretion, the
amount of this electrolyte in the body increases and
individual is in positive balance for that electrolyte
 If excretion exceeds its intake, its amount in the body
decreases and the individual is in negative balance
o For many electrolytes, kidneys are the sole or principal
route for excretion from the body
‒ Intake of water and many electrolytes is governed
mainly by a person's eating and drinking habits,
requiring the kidneys to adjust their excretion
rates to match the intakes of various substances
3. Regulation of body fluid osmolality
 Important for maintenance of normal cell volume in all tissues of the body
4. Regulation of arterial pressure
‒ Long-term regulation of arterial pressure by
excreting variable amounts of sodium and water.
The kidneys also contribute to short-term arterial
pressure regulation by secreting hormones and
vasoactive factors or substances (e.g., renin) that
lead to the formation of vasoactive products (e.g.,
angiotensin II)
‒ The kidneys secrete erythropoietin, which
stimulates the production of red blood cells by
hematopoietic stem cells in the bone marrow
7. Secretion metabolism and excretion of hormone
‒ The kidneys produce the active form of vitamin D,
1,25-dihydroxyvitamin D3 (calcitriol), by
hydroxylating this vitamin. Calcitriol is essential
for normal calcium deposition in bone and calcium
reabsorption by the gastrointestinal tract.
Calcitriol plays an important role in calcium and
phosphate regulation
 Hormones produced by the kidneys:
o Erythropoietin
 For RBC production
o Renin
 This is questionable because a hormone is produced by an
organ that is released in the blood and targets a distant organ
but in renin, it is produced by the kidneys and released in
the blood, but it targets a substrate, angiotensinogen.
o Calcitriol
 A metabolite of vitamin D3
8. Gluconeogenesis
‒ The kidneys synthesize glucose from amino acids
and other precursors during prolonged fasting
The kidneys perform their most important functions by filtering
the plasma and removing substances from the filtrate at
variable rates, depending on the needs of the body. Ultimately,
the kidneys "clear" unwanted substances from the filtrate (and
therefore from the blood) by excreting them in the urine while
returning substances that are needed back to the blood.
KIDNEY: FUNCTIONAL ANATOMY
‒ T12-L3
‒ Right kidney is lower than the left kidney
o because of the location of the liver
‒ Basic parts:
o Capsule
o Cortex
 Outermost portion of kidney
 Isotonic in nature (280-300 mmol/L)
o Medulla
 Innermost portion of kidney

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PHS101 RENAL PHYSIOLOGY 1 & 2 W3 T1 & 2

 Hypertonic in nature (1200-1400 mmol/L) BLOOD SUPPLY

 According to our lecture, if asked
which part of the kidney is hypertonic
in nature and the choices are inner
and outer medulla, inner medulla
should be the answer.
 Contains:
 Renal pyramids
 Columns of Bertin – in between the
renal pyramid
o Papilla, Calyces, Pelvis
 Minor calyces – connected to renal pyramids
that collectively will give rise to:
 Major calyces – collects the urine
and eventually forms the ureter
o Hilum
 Renal artery
 Renal vein
 Ureter – drains to the urinary bladder
 Blood flow to the kidneys is equivalent to about 25% (1.25 L/min) of the
cardiac output in resting individuals.
o However, kidneys constitute < 0.5% of total body weight.
Abdominal aorta  L and R Renal Artery  Segmental Artery 
Interlobar artery  Arcuate artery  Interlobular artery (cortical
radiate/radial artery)  Afferent Arteriole  Glomerular Capillaries
(60mmHg)  Efferent Arteriole  Peritubular Capillaries (18mmHg)
 Venule  Interlobular Vein  Arcuate Vein  Interlobar Vein 
Segmental Vein  Renal Vein  Inferior Vena Cava
22% of Cardiac Output (CO)
1,200 ml/min
(That is according to the PPT, but according to Berne and Levy, it is
25% of CO and 1.25 L/min)

 Afferent arterioles
o Contain important cells:
 Juxtaglomerular (JG) cells
 Granular cells
o Produces renin and erythropoietin factor
o Gives rise to glomerulus
 GROSS ANATOMY:
o In adults: o Regulates the pressure in the glomerulus
 115-170 g  When afferent arteriole dilates, hydrostatic pressure of
 11 cm long, 6 cm wide, 3 cm thick glomerulus increases
o Cortex – outer region  When afferent arteriole constricts, hydrostatic pressure of
o Medulla – inner region glomerulus drops
 Divided into conical masses – renal pyramids  Glomerulus
o A high pressure capillary bed (60-100 mmHg)
 Base: from corticomedullary border
 The average pressure of a normal capillary bed is 20 mmHg
 Apex: terminates in papilla which lies in minor calyx
o Filtration occurs here
(collect urine from each papilla)
 Efferent arterioles
 Minor calyx expand to 2-3 open ended pouches, the major
o When efferent arteriole constricts, it will generally increase the
calyces which feed into pelvis
hydrostatic pressure in the glomerulus and decrease the pressure in
 Pelvis represents upper expanded region of ureter peritubular capillaries
which carriers urine from pelvis into the urinary  Peritubular capillaries and vasa recta
bladder o Low pressure area (much lower than regular capillaries); 13-15
o Cortex & medulla – contains nephrons (functional unit), blood mmHg
vessels, lymphatics, and nerves o Reabsorption occurs here

 Characteristics of kidney: NERVE INNERVATION

o Retroperitoneal organ
‒ Renal nerves regulate renal blood flow (RBF) and glomerular
o Located around costovertebral angle
filtration rate (GFR) *to be discussed in the latter part of this
 Kidney stones can manifest as pain at the back area
trans*
‒ exclusively innervated by sympathetic nervous system
o that originated from the celiac plexus

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‒ renal nerves via adrenergic fibers (release norepinephrine and lie  Afferent arterioles, glomerular capillaries,
adjacent to the smooth muscle cells of the major branches of the efferent arteriole, podocytes, mesangial cells,
renal artery) as well as the afferent and efferent arterioles JG apparatus
o regulate renal blood flow and GFR via innervation of the
 Bowman’s Space
renal arterioles
 Bowman’s Capsule
o regulate water and salt reabsorption via innervation of the
renal tubules o Renal Tubular System
o stimulate renin secretion via innervation of the granular  Proximal Convoluted Tubule, Loop of Henle,
cells of the afferent arteriole Distal Tubule, Collecting Duct

 Nerve supply: RENAL CORPUSCLE

o Primarily composed of sympathetic fibers  CAPILLARY ENDOTHELIUM
o NO parasympathetic innervation
o Releases: ‒ highly-fenestrated
 Norepinephrine – vasoconstriction ‒ with pores 8 nanometer (80 angstrom) in diameter
 Dopamine – vasodilation ‒ 50x more permeable than skeletal muscle capillaries
o Renalase ‒ secretes Nitric Oxide and Endothelin-1
 An enzyme contained by the kidneys
 BASEMENT MEMBRANE
 Degrades the catecholamines
‒ have large spaces
‒ with Type IV Collagen, Lainin, Agrin, Perlecan,
 As far as renal transplant is concerned, Nerve supply is not anastomosed Fibronectin
because the kidney can function without nervous system influence due to  PODOCYTES
RENAL AUTOREGULATION (discussed in the latter part of this ‒ cells of capillary endothelium
trans)
‒ contains:
 foot processes
TWO SETS OF CAPILLARY BED  filtration slits
1. GLOMERULAR CAPILLARIES  filtration slit diaphragm
‒ High pressure capillary bed  MESANGIAL CELLS
‒ CHP = 60 mmHg ‒ found in between capillaries
‒ favor fluid filtration ‒ contractile, mediates filtration, take up immune
‒ highly-fenestrated complexes, involved in glomerular diseases
‒ responsible for GFR ‒ Functions (from Berne & Levy):
 provide structural support for the
2. PERITUBULAR CAPILLARIES
‒ Low pressure capillary bed glomerular capillaries
‒ CHP = 18 mmHg  secrete extracellular matrix
‒ favor fluid reabsorption  exhibit phagocytic activity by removing
‒ supplies O2 and glucose to the tubular cells macromolecules from the mesangium
‒ secretes Erythropoietin (EPO)  secrete prostaglandins and
proinflammatory cytokines
ULTRASTRUCTURE OF THE NEPHRON  may influence glomerular filtration rate
‒ basic unit of renal structure and function (GFR) by regulating blood flow through
‒ one million each kidney the glomerular capillaries or by altering
‒ kidneys cannot regenerate new nephrons the capillary surface area
o with renal injury, disease, or normal aging, there  Extraglomerular mesangial cells –
is a gradual decrease in nephron number mesangial cells located outside the
o kidneys undergo compensatory hypertrophy upon glomerulus between the afferent and
75% damage to nephrons efferent arterioles
‒ 40 y/o - ↓ 10 % every 10 years  JG CELLS
o After age 40, the number of functioning nephrons ‒ a.k.a. Glomerular cells of the afferent
usually decreases about 10 percent every 10 arterioles
years; thus, at age 80, many people have 40 ‒ found at the walls of the afferent arterioles
percent fewer functioning nephrons than they did ‒ secretes Renin
at age 40. This loss is not life threatening because  MACULA DENSA
adaptive changes in the remaining nephrons allow ‒ found in the walls of the Distal Convoluted Tubule
them to excrete the proper amounts of water, ‒ monitors sodium concentration in the DCT (and
electrolytes, and waste products consequently, blood pressure)
‒ serves as the Na+ sensor; detects the Na+
‒ Types of nephrons: concentration of the filtrate
o Cortical
o Juxtamedullary
‒ Parts of the nephron:
o Renal Corpuscle

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PHS101 RENAL PHYSIOLOGY 1 & 2 W3 T1 & 2

RENAL TUBULAR SYSTEM  Polycystin 1 (encoded by PKD1 gene) and polycystin 2 (PKD2 gene)
 Proximal Convoluted Tubule (PCT) o Expressed in the membrane of primary cilia and mediate entry of Ca2+
o Contains an extensively amplified apical membrane into cells
o PKD1 and PKD2 genes  flow-dependent K+ secretion by principal cells
(the ultrafiltrate or urine side of the cell) called the of the collecting ducts
brush border  A strong stimulus for secretion of K+ is increased flow of tubule
 Brush borders are present ONLY in the fluid in the collecting duct
proximal tubule o Increased flow bends the primary cilium in principal cells  activates
PKD1/PKD2 Ca2+ conducting channel complex and allows Ca2+ to enter
o Basolateral membrane (interstitial or blood side of
the cell increasing intracellular Ca2+
the cell) is highly invaginated  Increase in Ca2+ activates K+ channels in the apical plasma
 Invaginations contain many mitochindria membranes
 Loop of Henle (LH)  Secretion of K+ from cell to tubule fluid
o Descending Limb of the Loop of Henle
 Only water is reabsorbed
o Thin Ascending Limb of the Loop of Henle
 Solute reabsorption is passive
 Have poorly developed apical and
basolateral surfaces
o Thick Ascending Limb of the Loop of Henle
 Solute reabsorption is active
 Abundant mitochondria
 Extensive infoldings of the basolateral
membrane
 Distal Convoluted Tubule (DCT)
o First Part: Early Distal Tubule
o Second Part: Late Distal Tubule/Connecting Tubule,
Cortical Collecting Tubule
o Abundant mitochondria
o Extensive infoldings of the basolateral membrane
 Collecting Duct (CD)
TYPES OF NEPHRONS
o Medullary Collecting Tubule
o Collecting Duct CORTICAL NEPHRONS
‒ renal corpuscles are located in the outer region of the cortex
 The collecting duct is composed of 2 cell types:
‒ have short loops of Henle
o Principal cells
‒ most abundant
 Have a moderately invaginated basolateral membrane and
contain few mitochondria ‒ have peritubular capillaries
 Plays an important role in reabsorption of NaCl and secretion of ‒ In Berne & Levy, this type of nephrons are termed as “superficial
K+ nephrons”
o Intercalated cells
 Play an important role in regulating acid-base balance  This capillary network system:
 Have a high density of mitochondria o conveys oxygen and important nutrients to the nephron segments in
 One population secretes H+ the cortex
 Second population secretes HCO3- o delivers substances to individual nephron segments for secretion, and
o serves as a pathway for return of reabsorbed water and solutes to the
 All cells in the nephron EXCEPT intercalated cells have in their apical plasma circulatory system
membrane a single nonmotile primary cilium that protrudes in to the tubule
fluid.
o PRIMARY CILIA are: JUXTAMEDULLARY NEPHRONS
 mechanosensors (they sense changes in the rate of flow of ‒ renal corpuscles are located in the region of the cortex adjacent to
tubule fluid) the medulla
 chemosensors (the sense or respond to compounds in the ‒ have long loops of Henle
surrounding fluid)
o and extends deeper into the medulla
 and they initiate Ca2+ dependent signaling pathways, including
‒ less abundant
those that control kidney cell function, proliferation, differentiation,
‒ have vasa recta (and peritubular capillaries)
and apoptosis.
o Take note that the efferent arterioles in juxtamedullary
*** Please take note of this because this was not really mentioned during RENAL 1 nephrons forms not only a network of peritubular
discussion but was recalled during RENAL 3 discussion. *** capillaries by also a series of accompanying vascular loops
called the VASA RECTA
o Vasa recta descend into the medulla where they form
capillary networks that surround the collecting ducts and
ascending limbs of the loop of Henle
 The blood returns to the cortex via the
ascending vasa recta
‒ important in the concentration of urine

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PHS101 RENAL PHYSIOLOGY 1 & 2 W3 T1 & 2

 Less than 0.7% of renal blood flow (RBF) enters the vasa recta and these  GLOMERULAR FILTRATION
vessels serve important functions in renal medulla that include: o FILTRATION BARRIER:
o conveying oxygen and important metabolic substrates to support  Capillary endothelium
nephron function  First layer from the blood side
o delivering substances to the nephron for secretion  Has fenestrations
o serving pathway for return of reabsorbed water and solutes to the  Freely permeable to water, small solutes, and most
circulatory system proteins but is NOT permeable to RBCs, WBCs, and
o concentrating and diluting urine platelets
 Express negatively charged glycoproteins on their
surface, minimizing the filtration into Bowman’s space
CORTICAL JUXTAMEDULLARY of albumin and other plasma proteins
NEPHRONS NEPHRONS  Synthesize a number of vasoactive substances (NO
Percentage 75% 25% and endothelin 1 [ET-1]) important in control of renal
Location Renal Cortex Cortico-medullary plasma flow (RPF)
junction  Basement membrane
Loops of Henle Short Long  Has several layers
Capillary Network Peritubular Peritubular capillaries o Lamina rara interna – 1st layer from the
blood side
capillaries Vasa Recta
o Lamina densa
o Lamina rara externa
ULTRASTRUCTURE OF THE GLOMERULUS  The proteins present in the basement membrane are:
o Trimer of α1-6 collagen IV, laminin,
This part of the trans was purely copied from Berne & Levy 7 th edition: polyanionic proteoglycan, agrin, perlecan,
entactin, heparin-SO4, fibronectin
 First step of urine formation  passive movement of  Functions primarily as a charge-selective filter in
plasma ultrafiltrate from the glomerular capillaries to which the ability of proteins to cross the filter is based
on charge
Bowman’s space
 Bowman’s epithelium
 ULTRAFILTRATION:  Has podocytes
o Passive movement of fluid similar in composition to o Endocytic
plasma except for the fact that the ultrafiltrate o Finger like projections
protein concentration is much lower than that in the o Interdigitate to form slits so there will be slit
pores in between
plasma – from glomerular capillaries to Bowman’s
o Added info. (and was asked in our shifting
space exam about RENAL 1 &2): Membrane
 Embryonic: glomerular capillaries press into the closed end of proteins that provides integrity to the
proximal tubule  Bowman’s capsule  epithelial cells thin podocyte: nephrin, NEPH-1 and P-Cad
on the outside circumference of Bowman’s capsule forming the  Has slit pores/diaphragms
o Composed of nephrin (NPHS1), neph-1,
parietal epithelium  epithelial cells thicken and develop to
and PODOCIN (NPHS2) and intracellular
podocytes  visceral layer of Bowman’s capsule proteins that associate with the slit
 Bowman’s space – space between the visceral layer and diaphragm, including α-actinin-4 (ACTN4)
parietal layer which at the urinary pole of the glomerulus and CD2-AP
becomes the lumen of the proximal tubule  PODOCYTE FILTRATION SLITS primarily function as
size-selective barrier
o Urinary pole – where the proximal tubule joins
Bowman’s capsule ULTRASTRUCTURE OF THE
JUXTAGLOMERULAR APPARATUS
 JUXTAGLOMERULAR APPARATUS
o Component of an important feedback mechanism,
tubuloglomerular feedback mechanism
o also involved in autoregulation of RBF and GFR
 Structures:
o Macula densa of thick ascending limb
 Cells represent morphologically distinct
region of thick ascending limb
 This region passes through the angle
formed by the afferent and efferent
arterioles of the same nephron
 Cells contact the extraglomerular
mesangial cells and granular cells of
afferent arterioles
o Extraglomerular mesangial cells
o Renin- and angiotensin II- producing granular cells
of the afferent arteriole
 Contain smooth muscle myofilaments

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PHS101 RENAL PHYSIOLOGY 1 & 2 W3 T1 & 2

 Manufacture, store, and release renin in

response to signals associated with
decreased effective circulating
volume and reduced renal perfusion
 Renin is involved in proteolytic generation
of angiotensin II and ultimately in
secretion of aldosterone
 The reabsorption or secretion rate is the difference between the amount
filtered across the glomerular capillaries and the amount excreted in urine it
is calculated with the following equations:
o Filtered load = GFR x [plasma]
o Excretion rate = V x [urine]
o Reabsorption rate = filtered load – excretion rate
o Secretion rate = excretion rate – filtered load

CLINICAL CORRELATION
 Based on Fick’s principle (conservation of mass or mass
NEPHROTIC SYNDROME balance)
‒ Loss of normal podocyte structure (foot processes effacement)  Renal artery = single input source to kidney for substances not
‒ Increased permeability of the glomerular capillary to proteins synthesized by this organ
 Renal vein or ureter = constitute two principal output routes
 NEPHROTIC SYNDROME o The amount of substance that enters the kidney =
o produced by variety of disorders and is characterized by increased the amount that the kidneys in urine + the amount
permeability of glomerular capillaries to proteins and by loss of normal that leaves the kidneys in renal venous blood
podocyte structure  Emphasizes the excretory function of the kidneys
o augmented permeability to proteins in increased urinary protein o Considers only the rate at which a substance is
excretion = proteinuria excreted into urine and NOT its rate of return to the
o individuals with this syndrome also develop: systemic circulation in the renal vein
 hypoalbuminemia  Can be used to measure GFR and RPF and determine whether
 generalized edema a substance is reabsorbed or secreted along the nephron

CONGENITAL NEPHROTIC SYNDROME Formation of urine involves 3 processes:

‒ Mutations in the gene encoding for NEPHRIN
1. Ultrafiltration of plasma glomerulus
‒ Absent slit diaphragms
o Remember: Plasma ultrafiltrate is DEVOID of
‒ Massive proteinuria
cellular elements such as RBCs and platelets and
is essentially protein FREE
ALPORT SYNDROME
2. Reabsorption of water and solutes from the ultrafiltrate
‒ Hereditary nephritis (autosomal recessive)
3. Secretion of selected solutes into tubular fluid
‒ Due to a defect in the type IV collagen which is a major
component of the GBM
‒ Thinning of the GBM
‒ Ineffective filtration barrier to proteins and RBCS
‒ S/SX: hematuria and proteinuria, progression to renal failure

 ALPORT SYNDROME
o characterized by hematuria (i.e., blood in urine) and progressive
glomerulonephritis
o glomerular basement membrane becomes irregular in thickness and
fails to serve as an effective filtration barrier to blood cells and protein

ASSESSMENT OF RENAL FUNCTION

RENAL CLEARANCE

Excretion = Filtration rate – Reabsorption rate +

Secretion rate

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PHS101 RENAL PHYSIOLOGY 1 & 2 W3 T1 & 2

 ↓GFR – kidney disease is progressing; knowledge of patient’s

GFR – essential in evaluating the severity and course of kidney
Almost 180L/day - amount of fluid filtered thru glomerular capillaries
disease
1L/day – excreted  Common substances used to estimate or measure the GFR:
o Creatinine
 Clearance has the dimensions of volume/time and it represents a volume of o Inulin
plasma from which all the substance has been removed and excreted into
urine per unit time
 Can be expressed using the equation:
o Ex: If substance is present in urine at a concentration of 100
mg/mL and urine flow rate is 1 mL/min, the excretion rate for this
substance is calculated as follows:
 Excretion rate = U x V  GFR range in normal adults:
 Excretion rate = 100 mg/mL x 1 mL/min o Males - 90-140ml/min
 Excretion rate = 100 mg/min o Females – 80-125ml/min
 C = (U x V)/P = (100 mg/min)/(1mg/mL) = 100  Not all substances used to measure GFR that enters the kidney
mL/min in renal arterial plasma is filtered at the glomerulus
o Although nearly all plasma that enters the kidneys in
 Concept of clearance is important because it can be used to measure GFR the renal artery passes through the glomerulus,
and RPF and determine whether a substance is reabsorbed or secreted approximately 10% does not
along the epithelium.  The portion of filtered plasma is termed
o If filtered load > excretion rate  net reabsorption of substance has the FILTRATION FRACTION
occurred
o If filtered load < excretion rate = net secretion of substance has
occurred FILTRATION FRACTION
 Determined as:

EFFECTIVE RENAL PLASMA FLOW

 Portion of filtered plasma

 Under normal conditions: 0.15- 0.20
 Extent of fluid loss from the plasma
 The extent to which plasma proteins are being concentrated
 This is the percent of plasma going to the kidney that is filtered
 Example:
o RPF – 630 mL/min
o GFR = 125 mL/min
o FF = 125/630 or 20%

Only 15% to 20% of the plasma that enters the glomerulus is actually filtered. The
remaining 80% to 85% continues on through the glomerular capillaries and into
the efferent arterioles and peritubular capillaries before finally returning to the
 Measurement of renal blood flow via the clearance principle:
systemic circulation via the renal vein.
o In order for the clearance principle to be used,
paraaminohippuric acid (PAH) clearance
should be determined  FILTRATION FRACTION
o CPAH is determined because PAH is filtered and o Increases in filtration fraction produce increases in the
secreted protein concentration of peritubular capillary blood, which
leads to increased reabsorption in the proximal tubule
o
o Decreases in the filtration fraction produce decreases in
 NOTE FROM THE TRANSER: This is the process of determining CPAH. This the protein concentration of peritubular capillary blood and
was not mentioned during the lecture, so this is only a nice to know as a decreased reabsorption in the proximal tubule
future physician. What is important to know (and what was mentioned
during the lecture) is that PAH clearance should be determined in order
for clearance principle to be used.
TWO METHODS FOR QUANTIFICATION OF GFR
o PROCESS:
 Patient is infused with PAH and allow the patient to be in steady  Any substance that meets the ff. criteria can serve as a means
state so that the PAH will be filtered and secreted or distributed a measurement for the GFR:
in the body o Freely filtered across the glomerulus into the
 Get the blood and urine sample of the patient and determine Bowman’s space
the PAH concentration for each o Not reabsorbed or secreted by the nephron
 1 mL/min is the urine flow rate o Not metabolized or produced by the kidney
 Plot the values and you’ll get the clearance for PAH  Additional from Berne & Levy:
 REMEMBER that clearance for PAH = Renal Plasma Flow o Achieve a stable plasma concentration
(RPF) o Does not alter GFR

GLOMERULAR FILTRATION RATE

 Sum of the filtration rates of all functioning nephrons
o Aggregate index of kidney function

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PHS101 RENAL PHYSIOLOGY 1 & 2 W3 T1 & 2

IMPORTANCE OF DETERMINING GFR:

 Because GFR reflects renal function, we can know if the patient will
have renal failure
o If GFR is 25% or below, there is a renal failure
o So if we have a normal GFR of 120 mL/min, then the
patient has 30 mL/min GFR, then he has a renal failure and
you are a candidate for dialysis

1. Use of inulin
 The gold standard in determining filtration rate
 This is done by getting the clearance of inulin because it is
equal to the GFR
o Inulin is filtered only NOT secreted nor reabsorbed
 Infuse the subject with inulin and allow him to be in steady
state
 How is it done?
o Remember the clearance method:
 C=UV/P
o Get a blood and urine sample
o Determine the plasma and urine concentration of
inulin
 CREATININE CLEARANCE (CrCl) is used to estimate GFR in clinical
o Plot the values then compute practice
 Example: o Synthesized at a relatively constant rate
 C(inulin) = (120 mg/mL x o Amount produced is proportional to the total muscle mass
1mL/min)/1mg/mL  However, creatinine is not a perfect substance for measuring GFR because
 C(inulin) = 120 mL it is secreted to a small extent by the organic cation secretory system in the
proximal tubule
o If the clearance of inulin is 120 mL/min, then it is o Error introduced = approximately 10%
equal to the GFR o But the method used to measure the plasma creatinine concentration
 NOTE: Inulin is not normally used in the clinic because of its (Pcr) overestimates the true value of 10%
availability and cost o Two errors cancel each other, and in most clinical situations, CrCl
provides a reasonably accurate measure of GFR
2. Creatinine estimation
 Creatinine is a byproduct of normal skeletal muscle creatine FACTORS AFFECTING FILTERABILITY OF
metabolism and is freely filtered across the glomerulus into
Bowman’s space MOLECULES
o It is normally generated by the body at a fairly
1. Size
constant rate and is not appreciably reabsorbed,
secreted, or metabolized by the cells of the nephron ‒ Substances with MW of up to approximately 5000 whose
after its filtration molecular radii are <15A will have a plasma filtrate ratio of 1
o Accordingly the amount of creatinine excreted in (freely permeable)
urine per minute is fairly constant at a steady state ‒ inversely proportional
and equals the amount of creatinine filtered at the ‒ 20 angstrom or less: filtered freely
glomerulus each minute ‒ >42 angstrom: not filtered at all
 This is normally used in the clinics
 Serum creatinine will estimate GFR NOTE FROM THE TRANSER:
 According to the PPT, substances whose molecular radii are <15 A are
freely filtered
 According to Guyton, it is 20 A or less that can be freely filtered
 According to Berne & Levy (7TH edition), it is substances with radii of
<18 A that are freely filtered

2. Shape
‒ For a given molecular weight, a slender and flexible
molecule will pass through the glomerular filtration barrier
more easily than a spherical non-deformable molecule

3. Electrical Charge
‒ The glomerular filtration barrier contains fixed polyanions
which repel negatively charged macromolecules
‒ Positive substances > Neutral substances > Negative
substance

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PHS101 RENAL PHYSIOLOGY 1 & 2 W3 T1 & 2

 For any given molecular radius, cationic molecules are more readily filtered o arterial pressure
than anionic molecues o afferent arteriolar resistance
o The reduced filtration rate for anionic molecules is explained by the o efferent arteriolar resistance
presence of negatively charged glycoproteins on the surface of all
components of the glomerular filtration barrier
Because most plasma proteins are negatively charged, the negative ↑ Glomerular
o ↑ Arterial pressure Hydrostatic Pressure
↑ GFR
charge on filtration barrier restricts filtration of anionic proteins more
than the filtration of neutral and polyanionic proteins with molecular
radius between approximately 18 A to 42 A ↑ Afferent ↓ Glomerular
arteriolar ↓ GFR
Hydrostatic Pressure
resistance
Efferent arteriolar constriction depends on the severity of the
constriction; modest efferent constriction raises GFR, but severe
efferent constriction (more than a threefold increase in resistance)
tends to reduce GFR.

Hydrostatic pressure outside the capillaries (Bowman’s

Capsule)
- opposes filtration

↑ Hydrostatic Pressure ↓ GFR

↓ Hydrostatic Pressure ↑ GFR

In certain pathological states associated with obstruction of the urinary tract,

Bowman’s capsule pressure can increase markedly, causing serious reduction of
GFR. For example, precipitation of calcium or of uric acid may lead to “stones” that
lodge in the urinary tract, often in the ureter, thereby obstructing outflow of the
urinary tract and raising Bowman’s capsule pressure. This situation reduces GFR
RESTRICTIONS TO GLOMERULAR FILTRATION OF MOLECULES and eventually can cause hydronephrosis (distention and dilation of the renal pelvis
SUBSTAN MOLECULA MOLECULA [FILTRATE]/[WATE and calyces) and can damage or even destroy the kidney unless the obstruction is
CE R WEIGHT R RADIUS R] relieved.
(nm)
Water 18 0.10 1.0
Glucose 180 0.36 1.0 Glomerular capillary colloid osmotic pressure
Inulin 5,000 1.4 1.0 - Opposes filtration
Hemoglobin 17,000 2.0 0.03 - Influenced by the arterial plasma colloid osmotic pressure and
Cationic 3.6 0.42 fraction of plasma filtered by the glomerular capillaries (filtration
dextran fraction). Increasing the arterial plasma colloid osmotic pressure
Anionic 3.6 0.15 raises the glomerular capillary colloid osmotic pressure, which in
dextran turn decreases the GFR.
Anionic 3.6 0.01
dextran Colloid osmotic pressure of the proteins in Bowman’s
Serum 69,000 3.6 0.001 capsule
albumin
 Promotes filtration

DYNAMICS OF ULTRAFILTRATION
 Ultrafiltration occurs because the starling forces combine to
drive fluid from the lumen of glomerular capillaries across the
filtration barrier and into Bowman’s space

Net Filtration Pressure

 Balance of hydrostatic and colloid osmotic forces acting across
the capillary membrane
 sum of the hydrostatic and colloid osmotic forces that either
favor or oppose filtration across the glomerular capillaries

Glomerular hydrostatic pressure

- promotes filtration
- 60 mm Hg under normal conditions
- primary means for physiological regulation of GFR
- determined by three variables:

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PHS101 RENAL PHYSIOLOGY 1 & 2 W3 T1 & 2

SUMMARY OF DIRECT DETERMINANTS OF GFR & FACTORS THAT INFLUENCE

GLOMERULAR Kf

 This is the product of the intrinsic permeability of the

glomerular capillary and the glomerular surface area available
for filtration
RENAL BLOOD FLOW
 Normal Kf is calculated to be about 12.5 ml/min/ mm Hg of ‒ 20 – 25% of the cardiac output (1,000 - 1250 ml/min)
filtration pressure o Cardiac output = 5,000 ml or 5 L
 Remember that the rate of glomerular filtration is considerably o Renal blood flow
greater in glomerular capillaries than in systemic capillaries = 1,000 ml (1 L) – 1250 ml (1.25 L)
o This is mainly because Kf is approximately 100 times = 20 – 25 % of CO
greater in glomerular capillaries o Renal plasma flow = 550 ml – 600 ml (55 – 60 % of
 GFR can be altered by changing Kf or by changing any of the whole blood)
starling forces ‒ Blood flow in the Renal Cortex > Renal Medulla
 In normal individuals, GFR is regulated by alterations in ‒ Exhibits Local Autoregulation at a BP between 75-
hydraulic pressure in the glomerular capillaries that are mainly 160mmHg
mediated by changes in afferent and efferent arteriolar
pressure ‒ Determinants of renal blood flow:
o Hydrostatic and hydraulic pressure are the same.
The PPT that we had during our lec used the term
hydrostatic but in Berne & Levy 7th edition, hydraulic
pressure was used.
 Hydraulic pressure inside the glomerular capillaries (PGc) are
affected in 3 ways:  Renal Blood Flow (RBF) functions:
o Changes in afferent arteriolar resistance o indirectly determines glomerular filtration rate (GFR)
 ↓ resistance = ↑ PGc and GFR o modifies rate of solute and water absorption by the proximal tubule
 ↑ resistance = ↓ PGc and GFR o participates in concentration and dilution of urine
o Changes in efferent arteriolar resistance o delivers O2, nutrients, and hormones to cells along the nephron and
 ↓ resistance = ↓ PGc and GFR returns CO2, reabsorbed fluid, and solutes to the general circulation
 ↑ resistance = ↑ PGc and GFR o delivers substrates for excretion in urine
o Changes in renal arteriolar pressure
 ↑ blood pressure = ↑ PGc and GFR
 ↓ blood pressure = ↓ PGc and GFR  Remember that blood flow in any organ can be determined by the Ohm’s
Law:
o Q = ∆P/R
Although increased Kf raises GFR and decreased Kf reduces GFR, changes in Kf  Q = blood flow
probably do not provide a primary mechanism for the normal day-to-day regulation  P = mean arterial pressure minus venous pressure for that
of GFR. Some diseases, however, lower Kf by reducing the number of functional organ
glomerular capillaries (thereby reducing the surface area for filtration) or by  resistance to flow through that organ
increasing the thickness of the glomerular capillary membrane and reducing its
hydraulic conductivity. For example, chronic, uncontrolled hypertension and
diabetes mellitus gradually reduce Kf by increasing the thickness of the glomerular
capillary basement membrane and, eventually, by damaging the capillaries so REGULATION OF RENAL BLOOD FLOW
severely that there is loss of capillary function. INTRINSIC
‒ Inherent mechanism of the kidneys in maintaining renal blood
flow and GFR at a relatively constant level over an arterial
pressure range of 90-180mmHg
‒ Operates on 2 mechanisms
1. Myogenic mechanism
2. Tubuloglomerular feedback

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PHS101 RENAL PHYSIOLOGY 1 & 2 W3 T1 & 2

EXTRINSIC ‒ Adenosine – vasoconstricts afferent arteriole

‒ Influenced by certain hormones and sympathetic activity ‒ Nitric Oxide – vasodilates afferent arteriole

PRESSURE PROFILE If BP is low (75mmHg)

Low BP  Low GC Hydrostatic Pressure  Decreased GFR
 Renal Artery: 100mmHg (<125ml/min)  Detected by Macula Densa
 Glomerulus: 70 mmHg Macula Densa increases secretion of:
 Efferent arteriole: 18mmHg  Angiotensin II (via RAAS stimulation)
 Peritubular capillaries: 15mmHg o Vasoconstricts EFFERENT Arteriole 
 Interlobar vein: 10mmHg Increases GFR back to normal (125ml/min)
 Interstitium: 10 mmHg  Nitric Oxide
o Vasodilates AFFERENT Arteriole  Increases
MECHANISMS OF AUTOREGULATION GFR back to normal (125ml/min)

(INTRINSIC) If BP is high (160mmHg)

High BP  High GC Hydrostatic Pressure  Increased GFR
(>125ml/min)  Detected by Macula Densa
 The phenomenon whereby GFR and RBF are maintained relatively constant Macula Densa increases secretion of:
between blood pressures of 90 and 180 mmHg, namely autoregulation, is  Adenosine
achieved by changes in vascular resistance, mainly through the afferent o Vasoconstricts AFFERENT arteriole 
arterioles of the kidneys. decreases GFR back to normal (125ml/min)
 Because both GFR and RBF are regulated over the same range of pressures
and because RBF is an important determinant of GFR, it is not surprising
that the same mechanisms regulate both flows.
 Two mechanisms are responsible for autoregulation of RBF and GFR:
o Myogenic mechanism
 mechanism that responds to changes in arterial pressure
o Tubuloglomerular feedback
 responds to changes in NaCl tubular fluid
 Both mechanisms regulate the tone of afferent arteriole (further differentiated
on the next page)

 Three points concerning autoregulation should be noted:

o Autoregulation is absent when arterial pressure is
less than 90 mmHg
o Autoregulation is not perfect
 RBF and GFR do change slightly as arterial
pressure varies
o Despite autoregulation, RBF and GFR can be As far as kidney is concerned, adenosine and ATP acts as a
changed by several hormones and by alterations in vasoconstrictor, but generally, they act as vasodilator.
sympathetic nerve activity that change in response
to alterations in the extracellular fluid volume (ECFV)
 RENAL AUTOREGULATION
o In renal transplant patient, nerve supply is not anastomosed
because the kidney can function without the nervous system
influence due to autoregulatory mechanism of the kidneys.
o The kidney should maintain a constant RBF and GFR, despite in
fluctuations of mean arterial pressure
o The autoregulatory range is a mean arterial pressure (MAP) of 90-
180 mmHg
 If MAP falls within the range, blood flow to the kidneys and
filtration rate are constant
 Blood flow to the kidneys is constant in spite of fluctuating
pressure. As we can see in the Ohm’s Law (Q = ∆P/R), if the
pressure changes, resistance must adjust to maintain
constant flow

TUBULOGLOMERULAR FEEDBACK
 A NaCl-dependent mechanism
 Involves a feedback loop
 Increased in GFR  increased in NaCl in the tubular fluid from
TAL to distal tubule  increased ATP and adenosine  afferent
arteriolar vasoconstriction  decreased in glomerular capillary
hydrostatic pressure  decreased in renal blood flow and GFR

‒ a.k.a. Macula Densa Feedback

‒ maintains GFR at a constant 125ml/min (autoregulates
GFR at a BP of 75-160mmHg)

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PHS101 RENAL PHYSIOLOGY 1 & 2 W3 T1 & 2

 When arterial pressure rises by the macula densa of

and renal afferent arterioles juxtaglomerular
stretch = contraction of apparatus and converted to
smooth muscle signals that affect afferent
 Increase in resistance arteriolar resistance and thus
offsets increase in pressure, GFR.
RBF, and therefore GFR  Increase in formation and
remains constant release of ATP and
adenosine by macula densa
cells which cases
vasoconstriction of afferent
arteriole and normalization
of GFR

 Example:
PRACTICAL APPLICATION:
 High CHO and CHON intake will activate the Tubuloglomerular feedback,
increasing RBF and GFR. Why?
o Increase CHO and CHON intake will cause a rise in plasma-
glucose and plasma-amino acid concentration
o All of these will be filtered in the kidneys
o The job of the tubular cells is reabsorbed all the glucose and
amino acids because the body needs it
o For every glucose and amino acid reabsorbed, Na must be
reabsorbed (SGLT transporters, etc.)
o Less sodium is left in the filtrate so it is detected by the macula
densa activating Tubuloglomerular feedback
MYOGENIC MECHANISM
‒ Pressure-sensitive mechanism
‒ Increased ABP  renal afferent arteriole stretches and contracts
vasoconstriction  increased in renal arteriolar resistance  offsets
the increased in ABP  renal blood flow and GRF remain at constant
level
o When the patient is severely dehydrated, what will happen to the
RBF?
 RBF goes down
o When the patient is anemic, what will happen to RBF?
 Anemia will cause the viscosity of the blood to be low, so the
resistance is decreased, increasing RBF if you only account
for viscosity because there are factors like oxygenation of the
blood.
o When the arterioles detect less oxygen in the blood, what happens
in the RBF?
 Arterioles dilate, increasing RBF
EXTRINSIC REGULATION
 Remember that myogenic mechanism and tubuloglomerular
feedback play key roles in maintaining RBF and GFR when
blood pressure is greater than 90 mmHg and ECFV is in normal
range. However, when ECFV changes sympathetic activities,
hormones exert major control over the situation
o These hormones include angiotensin II,
prostaglandins, NO, endothelin, bradykinin, ATP,
and adenosine
 Afferent and efferent arterioles are innervated by
sympathetic neurons
o Sympathetic tone is minimal when ECFV is normal
o When ECFV is reduced, sympathetic nerves release
norepinephrine and dopamine and circulating
epinephrine is secreted by the adrenal medulla
o Norepinephrine and epinephrine causes
vasoconstriction (binds to α-adrenoceptors
located in afferent arterioles)
 Activation of α-adrenoceptors ↓ RBF and
GFR

Myogenic mechanism
 Related to the intrinsic
property of vascular smooth
muscle – the tendency to
contract when stretched
Tubuloglomerular feedback
 Involves a feedback loop n
which a change in GFR leads
to alteration in the
concentratin of NaCl in
tubular fluid which is sensed
Angiotensin
 Produced systemically as well as locally within the kidneys
 Constricts the afferent and efferent arterioles
 Decreases both RBF and GFR
 Acts with norepinephrine, epinephrine and angiotensin II to
decrease RBF and GFR and thereby increasing blood pressure
and ECFV (as would occur in hemorrhage)
o Please see table 32-1, figure 33-21, and table 33-18
on page 15 & 16 (derived from Berne & Levy 7th ed.)
of this trans
Prostaglandins
 Do not play a major role in regulating RBF in healthy resting
individuals

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PHS101 RENAL PHYSIOLOGY 1 & 2 W3 T1 & 2

 During hemorrhage and reduced ECFV, prostaglandins are  Decreases resistance of afferent and efferent arterioles
produced locally within the kidneys and serve to increase RBF  Increases RBF and GFR
without changing GFR
 Nonsteroidal anti-inflammatory drugs (NSAIDS) such as Dopamine
ibuprofen and naproxen potently inhibit prostaglandin  Produced by the proximal tubule
synthesis  Vasodilator substance
o Thus, administration of these drugs during renal  Role in kidney: increases RBF and inhibits renin secretion
ischemia and hemorrhagic shock is contraindicated
because by blocking production of prostaglandins,
they decrease RBF and increase renal ischemia

Endothelin
 Potent vasoconstrictor secreted by endothelial cells of the renal
vessels, mesangial cells, and distal tubular cells in response to
angiotensin II, bradykinin,, epinephrine, and endothelial shear
stress
 Causes profound vasoconstriction of afferent and efferent
arterioles
 Decreases GFR and RBF
 Elevated in number of glomerular disease states (renal disease
associated with diabetes mellitus)

Bradykinin
 Kallikrein – proteolytic enzyme produced in kidneys which
cleaves circulating kininogen to bradykinin
 Bradykinin is a vasodilator that acts by stimulating the release of NO
and prostaglandins
 Increases RBF and GFR

Adenosine
 Produced in kidneys Remember this. This was included in our shifting.
 Vasoconstriction of afferent arteriole
 Reduces RBF and GFR Table 32-1. Major hormones that influence the GFR and RBF
 Important role in tubuloglomerular feedback STIMULUS EFFECT ON EFFECT ON
GFR RBF
Natriuretic peptides (NAP) Vasoconstrictors
 Secretion is caused by the cardiac atria Sympathetic ↓ ECFV ↓ ↓
nerves
 Brain natriuretic peptide (BNP) by the cardiac ventricles
Angiotensin II ↓ ECFV ↓ ↓
 Increases when ECFV is expanded and myocardial wall tension
Endothelin ↑ stretch, A-II, ↓ ↓
is increased bradykinin,
 Both ANP and BNP dilate afferent arteriole and constrict epinephrine;
efferent arteriole ↓ECFV
 Provides modest increase in GFR with little change in RBF Vasodilators
Prostaglandins ↓ ECFV; ↑ shear No change or ↑
(PGE1, PGE2, stress, A-II ↑
Adenosine triphosphate (ATP)
PGI2)
 Can have bidirectional effects on both RBF and GFR Nitric Oxide ↑ shear stress, ↑ ↑
 Under some conditions, it constricts afferent arteriole (NO) Acetylcholine,
 Reduces RBF and GFR Histamine,
 May play a role in tubuloglomerular feedback Bradykinin, ATP
 Under other conditions, it may stimulate NO production and Bradykinin ↑Prostaglandins, ↑ ↑
have directionally opposite effects, increasing both RBF and ↓ ACE
Natriuretic ↑ECFV ↑ No change
GFR
Peptides (ANP,
BNP)
Glucocorticoids
 Increases both GFR and RBF when administrated with GFR = Glomerular Filtration Rate
RBF = Renal Blood Flow
therapeutic doses
ECFV = Extracellular Fluid Volume
ACE = Angiotensin Converting Enzyme
Histamine AII = Angiotensin II
 Modulates RBF during resting state and during inflammation
and injury

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PHS101 RENAL PHYSIOLOGY 1 & 2 W3 T1 & 2

Active Transport
 Needs ATP
 Involves three processes:

1. Tm- limited (Transport Maximum)

 Substances that are actively reabsorbed
 Rate of transport is limited due to the saturation of the
specific transport system when the tubular load exceeds the
capacity of the carrier protein
 Glucose transport in the proximal tubule
 Carrier depended transport modes
 Substances handled by transport maxima:
o Glucose (SGLT, GLUT)
o Amino acids (Na-Amino acid transporters)
o Phosphate (PO4), Sulfate (SO4)
o Vitamin C
o Malate, lactate, aceto-acetate, beta-hydroxybutarate
 Properties of carrier mediated transport are exhibited:
o Saturation
 All of the active sites are filled up by
substrate
o Competition/inhibition
 An inhibitor can decrease transport rate
o Specificity
 Transporter can only transport specific
molecule

AGENTS WITH HIGH TM AGENTS WITH LOW TM

 Less reabsorbed
FIGURE 33-21.  More reabsorbed  More excreted
 Less excreted  Greater clearance
 Lesser clearance  Na, Cl, HCO3
This table is a summary of this figure by the transer. Also please  Glucose, amino acids,
remember that constriction of either afferent and efferent arteriole lactate, sulfate, phosphate
causes RBF to decrease and the other way around when it dilates.
Transport Maximum for Glucose:
Afferent Efferent RBF GFR Normally, 100% of the filtered glucose is reabsorbed
arteriole arteriole Transport maximum is 375 mg/min
Constricts Normal ↓ ↓ Glucose threshold is at 250mg/min or a plasma glucose concentration of 200mg/ml
Normal Constricts ↓ ↑
Normal Dilates ↑ ↓
Dilates Normal ↑ ↑ CLINCAL APPLICATION:
When you have DM, blood sugar goes up as high as 300-500 mg/dL.
Glucose transporters (SGLT and GLUT) are saturated. If the carriers are saturated,
BASIC PROCESSES IN TUBULAR the rate of transport becomes constant at maximum rate. Even if the concentration of
REABSORPTION glucose increases, transport rate will still be the same because transport maxima is
reached
Passive Transport
- Diffusion of substances along or down an Any excess glucose that is not accommodated by the carriers will go out
electrochemical/osmotic gradient in the urine = GLUCOSURIA
- Passive reabsorption of water by osmosis is coupled to sodium
- Active reabsorption of Na is closely coupled to passive
reabsorption of Cl through paracellular route 2. Gradient-limited
- Urea is passively reabsorbed in the urea concentration  Substances that are passively reabsorbed
gradient in the inner medullary collecting duct facilitated by  Rate of transport depends on the electrochemical gradient,
urea transporters permeability of the membrane and the tubular flow rate
 Na reabsorption in the proximal tubule
 THREE STEPS IN NET ABRSORPTION OF NA+
o Na+ diffuse across the luminal apical membrane down an  Depends on the gradient established and the time the fluid is
electrochemical gradient in contact with the epithelium
o Transported across the basolateral membrane against an  HCO3 and Na are actively transported this way
electrochemical gradient
o Na+ water and other substance are reabsorbed from the
interstitial fluid into the peritubular capillaries by
ultrafiltration

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PHS101 RENAL PHYSIOLOGY 1 & 2 W3 T1 & 2

 High concentration gradient = faster rate of transport especially for HCO3 and  Aldosterone – Na and H2O and a little
Na. bit of K
 When the flow of the filtrate is fast, rate of reabsorption is low because there  ANP & Angiotensin II – Na and H2O
is less time for the fluid to be in contact with the tubular cells.  PTH, Vit. D &Calcitonin = Ca and PO4
 Slower flow means more time for the tubular cells to pick up ions.
 If the filtered load > excretion rate, net reabsorption has occurred:
o For example, the filtered load if plasma glucose level is 200
3. Pinocytosis mg/dL = amount of glucose present in the Bowman’s space will
 Simplest be 200 mg/dL so when you get a urine sample, glucose will be
 This is how small polypeptides are being handled zero
 When polypeptides are filtered, they are pinocytosed by the  If this FL = 200 and the ER = 0 so FL is greater,
cells therefore glucose is reabsorbed

LIMITATIONS OF TRANSPORT TABLE FROM OUR LECTURER’S PPT. THIS IS THE FILTRATION, REABSORPTION
AND EXCRETION RATES OF DIFFERENT SUBSTANCES BY THE KIDNEYS
 Is linked to Hydrolysis of ATP
 The primary active transporters in kidney include:
o Na+K+ ATPase
o Hydrogen ATPase
o Hydrogen K+ ATPase
o Calcium ATPase

Remember that the smaller the amount of filtrate, the more

impermeable the substance is to filtration and vice versa.

REVIEW QUESTIONS
These questions were asked by Dr. Memoracion, so please take note!

1. What is the principal size-selective barrier? Podocyte filtration

slits
QUANTIFICATION OF REABSORPTION
AMOUNT REABSORBED = AMOUNT FILTERED – 2. What is the principal charge-selective barrier/major electrostatic
AMOUNT EXCRETED barrier? Glomerular basement membrane

 Rx = (GFR X Px) – (Ux x V) 3. What happens to the substance if QF > QE? Reabsorption

o GFR = glolmerular filtration rate 4. What happens to the substance if QF < QE? Secretion
o Px = plasma concentration of the substance
o Ux = urine concentration of substance
o V = urine flow rate

Factors Affecting Tubular Reabsorption

1. FLOW RATE
o If flow rate is fast = reabsorption rate is slow
2. OSMOTIC PRESSURE
o If the osmotic pressure of the filtrate is high =
reabsorption rate decrease
 This is because fluid goes to the filtrate
3. HORMONAL INFLUENCE
o there is a wide variety of hormones that will affect
handling wide variety of substances
 ADH – water

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