Renal physiology bpums

Renal physiology- Dr. Kh.
Pourkhalili
1
Renal physiology
Presented by:
Dr. Khalil Pourkhalili
Bushehr University of Medical Sciences
(BPUMS)
Faculty of medicine
Bushehr University of Medical Sciences

Pourkhalili
2
B.P.U.M.S
 Regulation of water and electrolyte balance
 Excretion of metabolic waste
 Excretion of bioactive substances (Hormones and many
foreign substances, specifically drugs)
 Regulation of arterial blood pressure
 Regulation of red blood cell production
 Regulation of vitamin D production
 Gluconeogenesis
 Acid-base balance
Renal functions

Pourkhalili
3
B.P.U.M.S
 Position: the kidneys are paired organs that lie on the posterior wall
of the abdomen behind the peritoneum
 Weight: 115-170 g (Mean 150 g)
 Size: 11 cm long, 6 cm wide, and 3 cm thick
Anatomy of the kidneys and urinary system

Pourkhalili
4
B.P.U.M.S
 Major parts:
 Cortex
 Medulla
 Outer medulla
 Inner medulla
 Minor calyx
 Major calyx
 Pelvis

Pourkhalili
5
Two parts in kidney
B.P.U.M.S

Pourkhalili
6
B.P.U.M.S
 Blood flow to the two kidneys is equivalent to about 22% (1.1
L/min) of the cardiac output in resting individuals.
 Renal artery → interlobar artery → arcuate artery →
interlobular artery (cortical radial arteries) → afferent
arteriole → glomerular capillaries (glomerulus) → efferent
arteriole → peritubular capillaries, which supply blood to
the nephron.
 Interlobular vein → arcuate vein → interlobar vein →
renal vein.
Blood flow to the kidneys

Pourkhalili
7
B.P.U.M.S
Blood flow to the kidneys

Pourkhalili
8
B.P.U.M.S
 Number of nephrons in each human kidney:
 1-1.2 million nephrons, which are hollow tubes composed of a single cell
layer.
 The nephron consists of two parts
1. Renal corpuscle (glomerular capillaries and Bowman's capsule)
2. A long tubule which consists of:
 Proximal tubule
 Loop of Henle (DTL, ATL & TAL)
 Distal tubule
 Collecting duct system.
Nephron as functional unit in the kidney

Pourkhalili
9
B.P.U.M.S
 Macula densa
 Near the end of the thick ascending limb, the nephron passes between the
afferent and efferent arterioles of the same nephron. This short segment of
the thick ascending limb is called the macula densa.

Pourkhalili
10
B.P.U.M.S
Distal tubule
Cortical collecting tubule
Medullary collecting tubule
Collecting duct

Pourkhalili
11
B.P.U.M.S
The nephron

Pourkhalili
12
B.P.U.M.S
 Cortical nephrones (70-80 %)
 Juxtamedullary nephrons (20-30 %) (longer loop of Henle and
the efferent arteriole forms not only a network of peritubular
capillaries but also a series of vascular loops called the vasa
recta).
 The juxtamedullary nephrons are important for urine concentration.
Types of nephrons

Pourkhalili
13
Two types of nephrons
B.P.U.M.S

Pourkhalili
14
Two types of nephrons
B.P.U.M.S

Pourkhalili
15
B.P.U.M.S
 Less than 0.7% of the renal blood flow (RBF) enters the
vasa recta
 Functions of vasa recta:
 Conveying oxygen and important nutrients to nephron segments
 Delivering substances to the nephron for secretion
 Serving as a pathway for the return of reabsorbed water and solutes to the
circulatory system
 Concentrating and diluting the urine
Role of vasa recta

Pourkhalili
16
B.P.U.M.S
Vasa recta

Pourkhalili
17
B.P.U.M.S
 Proximal tubule cells: have an extensively amplified apical
membrane called the brush border (due to the presence of
many microvilli) , which is present only in the proximal tubule.
The basolateral membrane (the blood side of the cell) is
highly invaginated. These invaginations contain many
mitochondria.
 Cells of descending and ascending thin limbs of Henle's
loop: have poorly developed apical and basolateral surfaces
and few mitochondria.
 Cells of the thick ascending limb and the distal tubule:
have abundant mitochondria and extensive infoldings of the
basolateral membrane.
 The collecting duct cells: principal cells (P cells)and
intercalated cells (I cells).
Nephron cells

Pourkhalili
18
B.P.U.M.S
 Principal cells have a moderately invaginated basolateral
membrane and contain few mitochondria. Principal cells play an
important role in reabsorption of NaCl and secretion of K+.
 Intercalated cells, which play an important role in regulating acid-
base balance, have a high density of mitochondria.
- One population of intercalated cells secretes H+ (i.e., reabsorbs
HCO3-), and a second population secretes HCO3- .
 Inner medullary collecting duct cells: Cells of the inner
medullary collecting duct have poorly developed apical and
basolateral surfaces and few mitochondria.

Pourkhalili
19
B.P.U.M.S

Pourkhalili
20
B.P.U.M.S

Pourkhalili
21
B.P.U.M.S
Ultrastructure of the renal corpuscle
The renal corpuscle consists of:
1- Glomerulus or glomerular capillaries
2- Bowman's capsule

Pourkhalili
22
B.P.U.M.S
Juxtaglomerular apparatus consists of:
 The macula densa of the thick ascending limb
 Extraglomerular mesangial cells
 Renin producing granular cells of the afferent arteriole
The juxtaglomerular apparatus is one component of the tubuloglomerular
feedback mechanism that is involved in the autoregulation of RBF and GFR.

Pourkhalili
23
B.P.U.M.S
1. The capillary endothelium of the glomerular capillaries
2. Basement membrane (The total area of glomerular capillary
endothelium across which filtration occurs in humans is about 0.8 m2)
3. A single-celled layer of epithelial cells (podocytes)
Filtration barrier

Pourkhalili
24
B.P.U.M.S
Filtration barrier

Pourkhalili
25
B.P.U.M.S
Filtration barrier

Pourkhalili
26
B.P.U.M.S
 The endothelium is fenestrated (contains 700-Å holes) and
freely permeable to water, small solutes (such as Na+, urea, and
glucose), and most proteins but is not permeable to red blood
cells, white blood cells, or platelets.
 Because endothelial cells express negatively charged
glycoproteins on their surface, they may retard the filtration of
very large anionic proteins into Bowman's space.
 In addition to their role as a barrier to filtration, the endothelial
cells synthesize a number of vasoactive substances (e.g., nitric
oxide [NO], a vasodilator, and endothelin-1 [ET-1], a
vasoconstrictor) that are important in controlling renal plasma
flow (RPF).
Role of endothelial cells

Pourkhalili
27
B.P.U.M.S
 The basement membrane, which is a porous matrix of
negatively charged proteins, including type IV collagen,
laminin, proteoglycans and fibronectin, is an important
filtration barrier to plasma proteins.
 The basement membrane is thought to function primarily
as a charge-selective filter in which the ability of proteins
to cross the filter is based on charge.*
Role of basement membrane

Pourkhalili
28
B.P.U.M.S
 The podocytes, have long finger-like processes that
completely encircle the outer surface of the capillaries.
 The processes of the podocytes interdigitate to cover the
basement membrane and are separated by apparent gaps
called filtration slits (slit pores).
 Each filtration slit is bridged by a thin diaphragm that contains
pores with a dimension of 40 × 140 Å.
 Filtration slits, which function primarily as a size-selective
filter, keep the proteins and macromolecules that cross the
basement membrane from entering Bowman's space.
Role of podocytes

Pourkhalili
29
B.P.U.M.S

Pourkhalili
30
Mesangial cells
B.P.U.M.S

Pourkhalili
31
B.P.U.M.S
 Nephrotic syndrome: is produced by a variety of disorders and is
characterized by an increase in permeability of the glomerular capillaries
to proteins
 Proteinuria
 Hypoalbuminemia
 Generalized edema
IN THE CLINIC

Pourkhalili
32
Filterability through the filtration barrier
 Effect of size
 Filterability of solutes is inversely related to their size
 Effect of charge
 Negatively charged large molecules are filtered less easily than positively
charged molecules of equal molecular size
B.P.U.M.S

Pourkhalili
33

Pourkhalili
34
B.P.U.M.S
 Filtration
 Reabsorption
 Secretion
Basic renal processes involved in urine formation
Excretion= Filtration – reabsorption + secretion

Pourkhalili
35
B.P.U.M.S
 Filtration, is the process by which water and solutes in the blood
leave the vascular system through the filtration barrier and enter
Bowman's space.
 Secretion, is the process of moving substances into the tubular
lumen from the cytosol of epithelial cells that form the walls of the
nephron.
 Reabsorption, is the process of moving substances from the
lumen across the epithelial layer into the surrounding interstitium.
 Excretion, means exit of the substance from the body (ie, the
substance is present in the final urine produced by the kidneys).
Excreted= Filtered – Reabsorbed + Secreted
Basic renal processes

Pourkhalili
36
B.P.U.M.S
Creatinine Sodium

Pourkhalili
37
B.P.U.M.S
Glucose PAH

Pourkhalili
38
Glomerular filtration-the first step in urine formation
 Composition of the glomerular filtrate
 Filtrate is essentially protein-free and devoid of cellular elements,
including red blood cells.
 Most salts and organic molecules, are similar to the concentrations
in the plasma.
 Exceptions include calcium and fatty acids, that are not freely filtered
because they are partially bound to the plasma proteins.
B.P.U.M.S

Pourkhalili
39
GFR is about 20 % of RPF
 RBF → 1100 - 1200 ml/min
 About 5–10% of RBF, flows down into the medulla
 RPF → 650 ml/min
 GFR → 125 ml/min (180 L/day)
 Filtration fraction = GFR/RPF (20 %)
B.P.U.M.S

Pourkhalili
40
Determinants of GFR
 Ultrafiltration occurs because the starling forces
 Rate of filtration = Kf x NFP
 Rate of filtration = Kf x (PGC – ΠGC) – (PBC – ΠBC)
 Kf = hydraulic permeability x surface area
 NFP = (PGC – ΠGC) – (PBC – ΠBC)
 The portion of filtered plasma is termed the filtration fraction and is
determined as: FF=GFR/RPF
B.P.U.M.S

Pourkhalili
41
B.P.U.M.S
Determinants of GFR

Pourkhalili
42
1. Increased PBS decreases GFR
2. Increased glomerular capillary Kf increases GFR
3. Increased ΠGC decreases GFR
 Two factors that influence the glomerular capillary colloid osmotic
pressure:
 The arterial plasma colloid osmotic pressure
 The filtration fraction
B.P.U.M.S
Determinants of GFR

Pourkhalili
43
4. Increased glomerular capillary hydrostatic pressure increases
GFR (PGC is the primary regulator of GFR)
 PGC is determined by three variables, each of which is under
physiologic control:
 Arterial pressure
 Afferent arteriolar resistance
 Efferent arteriolar resistance
B.P.U.M.S
Determinants of GFR

Pourkhalili
44
B.P.U.M.S
In normal individuals, the GFR is regulated by alterations in PGC that are
mediated mainly by changes in afferent or efferent arteriolar resistance.

Pourkhalili
45
B.P.U.M.S
Determinants of GFR
Kf can be altered by the mesangial cells, with contraction of these
cells producing a decrease in Kf that is largely due to a reduction in the
area available for filtration.

Pourkhalili
46
Factors affecting the GFR
B.P.U.M.S

Pourkhalili
47
B.P.U.M.S
The following pressure measurements were obtained from within the
glomerulus of an experimental animal:
Glomerular capillary hydrostatic pressure = 50 mm Hg
Glomerular capillary oncotic pressure = 26 mm Hg
Bowman’s space hydrostatic pressure = 8 mm Hg
Bowman’s space oncotic pressure = 0 mm Hg
Calculate the glomerular net ultrafiltration pressure (positive
pressure favors filtration; negative pressure opposes filtration).
A. +16 mm Hg B. +68 mm Hg C. +84 mm Hg
D. 0 mm Hg E. −16 mm Hg F. −68 mm Hg
G. −84 mm Hg
Question

Pourkhalili
48
B.P.U.M.S
 RBF: 22-25% of the cardiac output or near 1100-1200 ml/min, 4 ml/min/gr
 Blood flow is higher in the renal cortex and lower in the renal medulla.
 About 5–10% of RBF, flows from efferent arterioles down into the medulla.
Renal blood flow
(ml/min/gr)

Pourkhalili
49
B.P.U.M.S
1. Pressure difference across renal vasculature
2. Total renal vascular resistance
 RBF=

 Like most other organs, the kidneys regulate their blood flow by
adjusting vascular resistance in response to changes in arterial
pressure.
 The afferent arteriole, efferent arteriole, and interlobular artery are
the major resistance vessels in the kidneys and thereby determine
renal vascular resistance
Determinants of renal blood flow

Pourkhalili
50
B.P.U.M.S
Renal resistance vessels

Pourkhalili
51
Physiologic control of GFR and RBF
 The determinants of GFR that are most variable and
subject to physiologic control include:
 PGC
 ΠGC
 These variables, in turn, are influenced by:
 Sympathetic nervous system
 Hormones and autacoids
 Feedback controls that are intrinsic to the kidneys
B.P.U.M.S

Pourkhalili
52
Sympathetic nervous system activation decreases GFR
 Strong activation of the renal sympathetic nerves
can constrict the renal arterioles (α1) and decrease
renal blood flow and GFR.
 Severe hemorrhage
 Brain ischemia
 Moderate or mild sympathetic stimulation has little
influence on renal blood flow and GFR.
 Reflex activation of the sympathetic nervous system resulting from
moderate decreases in pressure
B.P.U.M.S

Pourkhalili
53
Hormonal and autacoid control of renal circulation
1. Norepinephrine, epinephrine (a1 receptors) and
endothelin constrict renal blood vessels and decrease
GFR.
2. Angiotensin II preferentially constricts efferent arterioles,
thus:
 Increased angiotensin II levels raise glomerular hydrostatic pressure while
reducing renal blood flow.
 It should be kept in mind that increased angiotensin II formation usually
occurs in circumstances associated with decreased arterial pressure or
volume depletion, which tend to decrease GFR.
 In these circumstances, the increased level of angiotensin II, by constricting
efferent arterioles, helps prevent decreases in glomerular hydrostatic
pressure and GFR
 At the same time, though, the reduction in renal blood flow caused by
efferent arteriolar constriction contributes to decreased flow through the
peritubular capillaries, which in turn increases reabsorption of sodium and
water
B.P.U.M.S

Pourkhalili
54
3. Endothelial-derived nitric oxide decreases renal
vascular resistance and increases GFR.
4. Prostaglandins and bradykinin tend to increase
GFR.
 Under stressful conditions, such as volume depletion or after surgery, the
administration of nonsteroidal anti-inflammatory drugs (NSAIDS), such as
aspirin, that inhibit prostaglandin synthesis may cause significant
reductions in GFR.
B.P.U.M.S
Hormonal and autacoid control of renal circulation

Pourkhalili
55
B.P.U.M.S
Hormones affect on RBF and GFR

Pourkhalili
56
B.P.U.M.S
 The phenomenon whereby RBF and GFR are maintained relatively constant
(despite blood pressure changes), named autoregulation, to allow precise control
of renal excretion of water and solutes.
 Autoregulation, is achieved by changes in vascular resistance, mainly through
the afferent arterioles of the kidneys.
 Importance of GFR autoregulation in preventing extreme changes in renal
excretion
Autoregulation of GFR and RBF

Pourkhalili
57
B.P.U.M.S
1. Tubuloglomerular feedback (role of adenosine and ATP)
 ATP and adenosine constricts the afferent arteriole, thereby returning GFR to
normal levels.
 ATP and adenosine also inhibit renin release by granular cells in the afferent
arteriole
2. Myogenic mechanism (role of pressure and stretch
activated cationic channels)
 Importance of autoregulation
 Autoregulation of GFR and RBF provides an effective means for uncoupling renal
function from arterial pressure, and it ensures that fluid and solute excretion remain
constant.
Mechanisms for autoregulation of RBF and GFR

Pourkhalili
58
B.P.U.M.S
Tubuloglomerular feedback

Pourkhalili
59
B.P.U.M.S
Tubuloglomerular feedback

Pourkhalili
60
B.P.U.M.S
 Autoregulation is absent when arterial pressure is less
than 80 mm Hg.
 Autoregulation is not perfect; RBF and GFR do change
slightly as arterial blood pressure varies.
 Despite autoregulation, RBF and GFR can be changed
by certain hormones and by changes in sympathetic
nerve activity.
Three points concerning autoregulation

Pourkhalili
61
B.P.U.M.S

Pourkhalili
62
B.P.U.M.S
A novel drug aimed at treating heart failure was tested in experimental
animals. The drug was rejected for testing in humans because it caused
an unacceptable decrease in the glomerular filtration rate (GFR). Further
analysis showed that the drug caused no change in mean arterial blood
pressure but renal blood flow (RBF) was increased. The filtration fraction
was decreased.
What mechanism is most likely to explain the observed decrease in GFR?
A. Afferent arteriole constriction B. Afferent arteriole dilation
C. Efferent arteriole constriction D. Efferent arteriole dilation
Question

Pourkhalili
63
Urine formation by the kidneys
tubular processing of the
glomerular filtrate
B.P.U.M.S

Pourkhalili
64
Reabsorption and secretion by the renal tubules
 Urinary excretion = Glomerular filtration - Tubular
reabsorption + Tubular secretion
 Tubular reabsorption is selective and quantitatively large
B.P.U.M.S

Pourkhalili
65
 Reabsorption of filtered water and solutes from the tubular
lumen across the tubular epithelial cells, through the renal
interstitium, and back into the blood
 Transcellular route
 Paracellular rute
B.P.U.M.S

Pourkhalili
66
Transport
 Passive transport
 Simple diffusion
 Facilitated diffusion (glucose in
basolateral membrane)
 Active transport
 Active reabsorption
 Primary active transport
(sodium-potassium ATPase pump)
 Secondary active transport
 Secondary active reabsorption
(glucose by sodium in PT)
 Active secretion
 Primary active secretion
 Secondary active secretion
(H+ by sodium in PT)
 Osmosis
 Pinocytosis
B.P.U.M.S

Pourkhalili
67
Basic mechanisms of transmembrane transport
B.P.U.M.S

Pourkhalili
68
Transport maximum
 Transport maximum for substances that are actively
reabsorbed
B.P.U.M.S
375 mg/min
250
375 mg

Pourkhalili
69
• The renal threshold for glucose is the plasma level at which the
glucose first appears in the urine in more than the normal minute
amounts. One would predict that the renal threshold would be about
300 mg/dL, that is, 375 mg/min (TmG) divided by 125 mL/min
(GFR). However, the actual renal threshold is about 200 mg/dL of
arterial plasma, which corresponds to a venous level of about 180
mg/dL. Figure 38–10 shows why the actual renal threshold is less
than the predicted threshold. The "ideal" curve shown in this
diagram would be obtained if the TmG in all the tubules was
identical and if all the glucose were removed from each tubule when
the amount filtered was below the TmG. This is not the case, and in
humans, for example, the actual curve is rounded and deviates
considerably from the "ideal" curve. This deviation is called splay.
The magnitude of the splay is inversely proportionate to the avidity
with which the transport mechanism binds the substance it
transports.

Pourkhalili
70
Transport maximum
 Transport maximum for substances that are actively
secreted
B.P.U.M.S

Pourkhalili
71
Reabsorption and secretion along nephron
 Proximal tubular reabsorption
 Normally, about 65 per cent of the filtered load of sodium and water and a
slightly lower percentage of filtered chloride are reabsorbed by the proximal
tubule
 Cells of the proximal tubule also secrete organic cations and organic anions
B.P.U.M.S

Pourkhalili
72
 In the first half of the proximal tubule, Na+ uptake into the cell is
coupled with either H+ (HCO3-) or organic solutes (glucose and AA)
B.P.U.M.S
First half of the proximal tubule

Pourkhalili
73
 In the second half of the proximal tubule, sodium is reabsorbed
mainly with chloride ions (para and transcellular) because of higher
chloride concentration (around 140 mEq/L compared to 105 in first
half)
B.P.U.M.S
Oxalate
HCO3-
Sulfate
Second half of the proximal tubule

Pourkhalili
74
Osmotic reabsorption of water across the PT
B.P.U.M.S
An important consequence of osmotic water flow across the proximal tubule
is that some solutes, especially K+ and Ca++, are entrained in the
reabsorbed fluid and thereby reabsorbed by the process of solvent drag.

Pourkhalili
75
B.P.U.M.S
Concentrations of solutes along the PT

Pourkhalili
76
 Solute and water transport in loop of henle
 Henle's loop reabsorbs approximately 25% of the filtered NaCl and 15-20 % of
the filtered water
B.P.U.M.S

Pourkhalili
77
 Distal Tubule
 The very first portion of the distal tubule forms part of the juxtaglomerular
complex
 The next part of the distal tubule referred to as the diluting segment
because it also dilutes the tubular fluid. It is virtually impermeable to water
and urea.
 Approximately 5 percent of the filtered load of sodium chloride is
reabsorbed in the early distal tubule.
B.P.U.M.S

Pourkhalili
78
Late distal tubule and cortical collecting tubule
 Principal cells
 Reabsorb sodium and water from the lumen and secrete potassium ions
into the lumen (sites of action of the potassium-sparing diuretics)
 Reabsorption of Na+ generates a negative luminal voltage, which provides
the driving force for reabsorption of Cl- across the paracellular pathway
B.P.U.M.S

Pourkhalili
79
 Reabsorb potassium ions and secrete H+ ions into the
tubular lumen
 Reabsorption of K+ is mediated by an H+,K+-ATPase
located in the apical cell membrane.
B.P.U.M.S
Intercalated cells

Pourkhalili
80
 Medullary collecting duct
 Medullary collecting ducts reabsorb less than 10 % of the filtered water and
sodium
 They are the final site for processing the urine and, therefore, play an extremely
important role in determining the final urine output of water and solutes.
 Special characteristics MCD:
 The permeability of the medullary collecting duct to water is controlled by the
level of ADH.
 Unlike the cortical collecting tubule, the medullary collecting duct is permeable to
urea.
 The medullary collecting duct is capable of secreting H+ against a large
concentration gradient, as also occurs in the cortical collecting tubule. Thus, the
medullary collecting duct also plays a key role in regulating acid-base balance.
B.P.U.M.S

Pourkhalili
81
B.P.U.M.S
Medullary collecting duct

Pourkhalili
82
B.P.U.M.S

Pourkhalili
83
Summary of concentrations of solutes in the tubular segments
B.P.U.M.S

Pourkhalili
84
Regulation of tubular reabsorption
 Glomerulotubular balance
 The ability of the tubules to increase reabsorption rate in response to
increased tubular load
 If GFR increases from 125 ml/min to 150 ml/min, the absolute rate of
proximal tubular reabsorption also increases from about 81 ml/min (65 per
cent of GFR) to about 97.5 ml/min (65 percent of GFR).
 Some degree of glomerulotubular balance also occurs in other tubular
segments, especially the loop of Henle.
 The importance of glomerulotubular balance:
 It helps to prevent overloading of the distal tubular segments when GFR
increases. And acts as a second line of defense to buffer the effects of
spontaneous changes in GFR on urine output. (The first line of defense,
tubuloglomerular feedback, which help prevent changes in GFR.)
B.P.U.M.S

Pourkhalili
85
Regulation of tubular reabsorption
 Hormonal control of reabsorption
 Aldosterone
 AII
 ADH
 ANP
 PTH
 Sympathetic stimulation (E, NE)
B.P.U.M.S

 Dilates the AA, constricts the EA and relaxes the mesangial cells,
Thus this increases pressure in the glomerular capillaries, thus
increasing the glomerular filtration rate (GFR), resulting in greater
excretion of sodium and water.
 Increases blood flow through the vasa recta which will wash the
solutes (NaCl and urea) out of the medullary interstitium.
 Decreases sodium reabsorption in the distal convoluted tubule
(interaction with Na-Cl cotransporter) and cortical collecting duct of the
nephron via cGMP dependent phosphorylation of Na channels.
 Inhibits renin secretion
 Reduces aldosterone secretion
 Relaxes vascular wall by elevation of cGMP
Pourkhalili
86
Regulation of tubular reabsorption- role of ANP
B.P.U.M.S

Pourkhalili
87
Peritubular capillary and renal interstitial fluid physical forces
 Reabsorption =Kf x Net reabsorptive force
B.P.U.M.S

Pourkhalili
88
B.P.U.M.S

Pourkhalili
89
Regulation of peritubular capillary physical forces
 The determinants of peritubular capillary reabsorption
1. Hydrostatic pressure of the peritubular capillaries which is
influenced by arterial pressure and resistances of the afferent and
efferent arterioles.
 ↑ Arterial pressure tend to raise peritubular capillary hydrostatic pressure
and decrease reabsorption rate.
 Increase in resistance of either the afferent or the efferent arterioles reduces
peritubular capillary hydrostatic pressure and tends to increase reabsorption
rate.
2. Colloid osmotic pressure of the plasma in peritubular capillaries
 ↑ Colloid osmotic pressure increases peritubular capillary reabsorption.
 The colloid osmotic pressure of peritubular capillaries is determined by:
 Systemic plasma colloid osmotic pressure
 Filtration fraction
3. Kf (Increases in Kf raise reabsorption)
4. Hormones (Aldosterone, AII, ADH, ANP, PTH)
B.P.U.M.S

Pourkhalili
90
B.P.U.M.S
Regulation of peritubular capillary physical forces

Pourkhalili
91
Renal interstitial hydrostatic and colloid osmotic
pressures
B.P.U.M.S

Pourkhalili
92
B.P.U.M.S
 The amount of substance that is filtered per unit time.
 For freely filtered substances, the filtered load is just the product of
GFR and plasma concentration.
 Sodium filtered load: 0.14 mEq/mL x 125 mL/min = 17.5 mEq/min.
Filtered load

Pourkhalili
93
B.P.U.M.S
 The volume of plasma from which that substance has been removed
and excreted into urine per unit time (volume/time).
 If a substance is present in urine at a concentration of 100 mg/mL and
the urine flow rate is 1 mL/min, the excretion rate for this substance is
calculated as follows:
 If this substance is present in plasma at a concentration of 1 mg/mL,
its clearance is as follows:
Clearance

Pourkhalili
94
B.P.U.M.S
A healthy 25-year-old woman was a subject in an approved research
study. Her average urinary urea excretion rate was 12 mg/min, measured
over a 24-hour period. Her average plasma urea concentration during
the same period was 0.25 mg/mL.
What is her calculated urea clearance?
A. 0.25 mL/min B. 3 mL/min
C. 48 mL/min D. 288 mL/min
Question

Pourkhalili
95
B.P.U.M.S
 GFR is an index of kidney function. Knowledge of the patient's
GFR is essential in evaluating the severity of kidney disease.
 The substance used for measuring GFR must:
Be freely filtered across the glomerulus into Bowman's space
Not be reabsorbed or secreted by the nephron
Not be metabolized or produced by the kidney
Not alter the GFR
Inulin and creatinine can be used to measure GFR.
Using clearance to estimate GFR

Pourkhalili
96
B.P.U.M.S
 Inulin clearance can be used to estimate GFR
Other substances that have been used clinically to estimate GFR include
radioactive iothalamate and creatinine.

Pourkhalili
97
Example
B.P.U.M.S

98
 Creatinine clearance can be used to estimate GFR
B.P.U.M.S

Pourkhalili
99
B.P.U.M.S
Correlation between plasma creatinine concentration and GFR

Pourkhalili
100
B.P.U.M.S
 If we know the GFR (as assessed from inulin clearance) and the
clearance of a given substance, then any difference between
clearance and GFR represents net secretion or reabsorption
(or, in a few rare cases, renal synthesis).
 If the clearance of a substance exactly equals the GFR (inulin
clearance), then there has been no net reabsorption or secretion.
 If the clearance is greater than the GFR, there must have been net
secretion.
 Finally, if the clearance is less than the GFR, there must have been
net reabsorption.
What can the clearance of a substance tell us?

Pourkhalili
101
B.P.U.M.S
 If a substance is completely cleared from the plasma, the clearance
rate of that substance is equal to the total renal plasma flow thus:
 Amount of the substance delivered to the kidneys by RPF equals to
amount of the substance excreted in the urine
 RPF x Ps = Us x V
 PAH clearance can be used to estimate RPF
 The characteristics of the substance used for measuring RPF:
 Its concentration in arterial and renal venous plasma should be measureable.
 It is not metabolized, stored, or produced by the kidney
 Does not itself affect blood flow
Using clearance to estimate RPF

Pourkhalili
102
PAH clearance can be used to estimate RPF
B.P.U.M.S

Pourkhalili
103
Example
B.P.U.M.S

Pourkhalili
104
 Effective renal plasma flow (ERPF)
 ERPF= Clearance of PAH (CPAH)
 Example
 UPAH: 14 mg/mL
 V urine: 0.9 mL/min
 PPAH: 0.02 mg/mL
 ERPF=?
B.P.U.M.S
PAH
PAH
P
VU
ERPF
.

Estimating renal plasma flow by PAH clearance
min/630
02.0
9.014
mlERPF 



Pourkhalili
105
 ERPF can be converted to actual renal plasma flow (RPF)
 Average PAH extraction ratio: 0.9
 Actual RPF=ERPF/extraction ratio=630/0.9=700 ml/min
 RBF = RPF ÷ (1 − Hct) = 700 ÷ (1-0.45)= 700 ÷ 0.55 = 1273
B.P.U.M.S
PAH
PAHPAH
PAH
P
VP
E


Conversion of ERPF to actual RPF
Extraction
ERPF
ActualRPF
%


Pourkhalili
106
Regulation of extracellular fluid
osmolarity and sodium
concentration
B.P.U.M.S

Pourkhalili
107
 Importance of osmolarity regulation
 Extracellular fluid sodium concentration and
osmolarity are regulated by the amount of
extracellular water.
 The body water in turn is controlled by:
 Fluid intake (thirst)
 Renal excretion of water
 In this chapter, we discuss specifically:
 Mechanisms that cause the kidneys to eliminate excess water by excreting
a dilute urine
 Mechanisms that cause the kidneys to conserve water by excreting a
concentrated urine
 Renal feedback mechanisms that control the extracellular fluid sodium
concentration and osmolarity
 Thirst and salt appetite mechanisms
B.P.U.M.S

Pourkhalili
108
Kidneys excrete excess water by forming a dilute urine
B.P.U.M.S

Pourkhalili
109
 Tubular fluid remains isosmotic in the proximal tubule
 Tubular fluid becomes dilute in the ascending loop of henle
 Tubular fluid in distal and collecting tubules is further diluted in the absence
of ADH.
B.P.U.M.S
Renal mechanisms for excreting a dilute urine

Pourkhalili
110
Kidneys conserve water by excreting a concentrated urine
 The human kidney can produce a maximal urine
concentration of 1200 to 1400 mOsm/L.
 Some desert animals, such as the Australian hopping
mouse, can concentrate urine to as high as 10,000
mOsm/L
 This allows the mouse to survive in the desert without
drinking water; sufficient water can be obtained through
the food ingested and metabolism.
B.P.U.M.S

Pourkhalili
111
B.P.U.M.S
The fact that the large amounts of water are reabsorbed into the cortex, rather
than into the renal medulla, helps to preserve the high medullary interstitial fluid
osmolarity.
Renal mechanisms for excreting a concentrated urine

Pourkhalili
112
Requirements for excreting a concentrated urine
1. High ADH Levels
 Osmoreceptors and ADH secretion
B.P.U.M.S

Pourkhalili
113
1. High ADH Levels
 Osmoreceptors and ADH secretion
B.P.U.M.S

Pourkhalili
114
2. Hyperosmotic renal medulla
 The process by which renal medullary interstitial fluid becomes
hyperosmotic:
a. Countercurrent mechanism (50 %)
 The countercurrent mechanism depends on the special anatomical arrangement of
the loops of Henle and the vasa recta
b. Urea recycling (40-50 %)
B.P.U.M.S

Pourkhalili
115
a. Countercurrent mechanism
 Countercurrent mechanism produces a hyperosmotic renal medullary
interstitium
 The major factors that contribute to the buildup of solute concentration
into the renal medulla are as follows:
1. Active transport of sodium ions and co-transport of potassium, chloride, and
other ions out of the thick portion of the ascending limb of the loop of Henle
into the medullary interstitium
2. Active transport of ions from the collecting ducts into the medullary interstitium
3. Facilitated diffusion of large amounts of urea from the inner medullary
collecting ducts into the medullary interstitium
4. Diffusion of only small amounts of water from the medullary tubules into the
medullary interstitium, far less than the reabsorption of solutes into the
medullary interstitium
B.P.U.M.S

Pourkhalili
116
Steps involved in causing hyperosmotic renal medula
B.P.U.M.S
Countercurrent multiplier system in the loop of Henle for producing
a hyperosmotic renal medulla

Pourkhalili
117
Role of distal tubule and collecting ducts in excreting a
concentrated urine
B.P.U.M.S
The fact that the large amounts of water are reabsorbed into the cortex, rather
than into the renal medulla, helps to preserve the high medullary interstitial fluid
osmolarity.

Pourkhalili
118
 Recirculation of urea from collecting duct to loop of henle
contributes to hyperosmotic renal medulla
B.P.U.M.S
b. Role of urea recycling

Pourkhalili
119
 Countercurrent exchange in the vasa recta preserves
hyperosmolarity of the renal medulla
 There are two special features of the renal medullary blood
flow that contribute to the preservation of the high solute
concentrations:
1. The medullary blood flow is low, accounting for less than 5 per cent of the
total renal blood flow. This sluggish blood flow is sufficient to supply the
metabolic needs of the tissues but helps to minimize solute loss from the
medullary interstitium.
2. The vasa recta serve as countercurrent exchangers, minimizing washout of
solutes from the medullary interstitium
B.P.U.M.S
Countercurrent exchange in the vasa recta

120
Countercurrent exchange in the vasa recta
B.P.U.M.S
Increased medullary blood flow can reduce urine concentrating ability

Pourkhalili
121
Antiduresis
B.P.U.M.S

Pourkhalili
122
Summary of urine concentrating mechanism and changes in osmolarity
in different segments of the tubules
B.P.U.M.S

Pourkhalili
123
Obligatory urine volume
 A normal 70-kilogram human must excrete about 600 milliosmoles
of solute each day.
 Maximal urine concentrating ability is 1200 mOsm/L
 Drinking 1 liter of seawater with a concentration of 1200 mOsm/L
would provide a total sodium chloride intake of 1200 milliosmoles.
 If maximal urine concentrating ability is 1200 mOsm/L, the amount
of urine volume needed to excrete 1200 milliosmoles would be 1200
milliosmoles divided by 1200 mOsm/L, or 1.0 liter.
 Why then does drinking seawater cause dehydration?
B.P.U.M.S

Pourkhalili
124
Osmolar clearances
 When the urine is dilute, water is excreted in excess of solutes.
 Conversely, when the urine is concentrated, solutes are excreted in
excess of water.
 Osmolar clearance (Cosm):
 The volume of plasma cleared of solutes each minute.
 For example:
 If Posm= 300 mosm/L, Uosm= 600 mosm/L, urine flow rate is 1 ml/min
(0.001 L/min)
 Osmolar clearance is 0.6 mosm/min divided by 300 mosm/L, or
0.002 L/min (2.0 ml/min).
 This means that 2 milliliters of plasma are being cleared of solute
each minute.
B.P.U.M.S

Pourkhalili
125
 Free-water clearance (CH20) is calculated as the difference between water
excretion (urine flow rate) and osmolar clearance:
 Thus, the rate of free-water clearance represents the rate at which solute-
free water is excreted by the kidneys.
 When free-water clearance is positive, excess water is being excreted by
the kidneys
 When free-water clearance is negative, excess solutes are being removed
from the blood by the kidneys and water is being conserved.
 Thus:
 When urine osmolarity is greater than plasma osmolarity, free-water
clearance will be negative, indicating water conservation
 When urine osmolarity is lower than plasma osmolarity, free-water
clearance will be positive, indicating that water is being removed from
plasma.
B.P.U.M.S
Free water clearances

Pourkhalili
126
Disorders of urinary concentrating ability
 Inappropriate secretion of ADH (Either too much or too little
ADH secretion)
 Impairment of the countercurrent mechanism.
 A hyperosmotic medullary interstitium is required for maximal urine
concentrating ability. No matter how much ADH is present, maximal urine
concentration is limited by the degree of hyperosmolarity of the medullary
interstitium.
 Inability of the distal tubule, collecting tubule, and collecting
ducts to respond to ADH.
B.P.U.M.S

Pourkhalili
127
 Failure to Produce ADH (Central diabetes insipidus)
 The treatment for central diabetes insipidus is administration of a synthetic
analog of ADH, desmopressin.
 Inability of the kidneys to respond to ADH
(Nephrogenic diabetes insipidus)
 The treatment for nephrogenic diabetes insipidus is to correct, if possible,
the underlying renal disorder.
B.P.U.M.S
Disorders of urinary concentrating ability

Pourkhalili
128
Control of ECF osmolarity and Na+ concentration
 Estimating plasma osmolarity from plasma sodium
concentration
 Because sodium and its associated anions (Cl-, HCO3-)
account for about 94 per cent of the solutes in the
extracellular compartment, plasma osmolarity can be
roughly approximated as:
 Posm=2.1 x Plasma sodium concentration
 Posm=2.1 x 142= 298 mosm/L
B.P.U.M.S

Pourkhalili
129
 Two primary systems regulating the concentration
of sodium and osmolarity of extracellular fluid:
1. The osmoreceptor-ADH system
2. The thirst mechanism
B.P.U.M.S

Pourkhalili
130
1. The osmoreceptor-ADH system
B.P.U.M.S

Pourkhalili
131
 CNS centers for thirst
1. Anteroventral wall of the third ventricle (AV3V)
 Subfornical organ
 OVLT
2. A small area located anterolaterally in the preoptic nucleus
 Stimuli for thirst
B.P.U.M.S
2. Role of thirst in controlling ECF osmolarity and Na cocentration

Pourkhalili
132
 Integrated responses of osmoreceptor-ADH and thirst mechanisms
in controlling extracellular fluid osmolarity and sodium concentration
B.P.U.M.S

Pourkhalili
133
Role of AII and aldosterone in ECF osmolarity and Na concentration
 Angiotensin II and aldosterone have little effect on sodium
concentration, because:
 Although these hormones increase the amount of sodium in the ECF, they
also increase the ECF volume by increasing reabsorption of water along
with the sodium.
B.P.U.M.S

Pourkhalili
134
B.P.U.M.S

Pourkhalili
135
B.P.U.M.S
Regulation of potassium excretion

Pourkhalili
136
Normal K intake, distribution and output from the body
B.P.U.M.S

Pourkhalili
137
Regulation of potassium excretion
 ECF K concentration: 4.2 ±0.3 mEq/L
 This precise control is necessary because many cell
functions are very sensitive to changes in extracellular
fluid potassium concentration.
 For instance, an increase in plasma potassium
concentration of only 3 to 4 mEq/L can cause cardiac
arrhythmias, and higher concentrations can lead to
cardiac arrest or fibrillation.
 Total ECF K → (14×4.2)→ 59 milliequivalents
 Total ICF K → (28×140)→ 3920 milliequivalents
B.P.U.M.S

Pourkhalili
138
Effect of adding or removing K to ECF
 The potassium in a single meal → as high as 50mEq
 Daily intake of K → 50 - 200 mEq/day
 Therefore:
 Failure to rapidly rid the extracellular fluid of the ingested potassium could
cause life-threatening hyperkalemia.
 Likewise, a small loss of potassium from the extracellular fluid could cause
severe hypokalemia.
B.P.U.M.S

Pourkhalili
139
Factors that can influence the distribution of K between the
intra- and extracellular compartments
 Insulin stimulates k uptake into cells by activating Na-K
ATPases in many cells
 Aldosterone increases potassium uptake into cells
 ↑ K intake → ↑ secretion of aldosterone → ↑ cell potassium uptake.
 ↑ Aldosterone secretion (Conn's syndrome) → hypokalemia.
 ↓ Aldosterone secretion (Addison's disease) → hyperkalemia due to
accumulation of potassium in ECF as well as to renal retention of K.
B.P.U.M.S

Pourkhalili
140
Factors that can influence the distribution of K
 B-adrenergic stimulation increases cellular uptake of
potassium probably by (up-regulating the activity of the
sodium-potassium pump)
 Acid-base abnormalities can cause changes in
potassium distribution
 Metabolic acidosis increases extracellular potassium concentration, in part
by causing loss of potassium from the cells.
 Metabolic alkalosis decreases extracellular fluid potassium concentration.
 ↑ H+ → ↓ activity Na-K ATPase pump → ↓cellular uptake of K and raises
extracellular K
B.P.U.M.S

Pourkhalili
141
Factors that can influence the distribution of K
 Cell lysis causes increased extracellular K concentration
 As occurs with severe muscle injury or with red blood cell lysis
 Strenuous exercise can cause hyperkalembia by
releasing potassium from skeletal muscle.
 Increased ECF osmolarity causes redistribution of K
from the cells to ECF.
 In diabetes mellitus, large increases in plasma glucose raise
extracellular osmolarity, causing cell dehydration and movement of
potassium from the cells into the extracellular fluid
B.P.U.M.S

Pourkhalili
142
Overview of renal potassium excretion
B.P.U.M.S

Pourkhalili
143
B.P.U.M.S

Pourkhalili
144
 Most of the day-to-day variation of potassium excretion is not due to
changes in reabsorption in the proximal tubule or loop of Henle but:
 Most daily variation in potassium excretion is caused by changes in
potassium secretion in distal and collecting tubules
 Thus, most of the day-to-day regulation of potassium excretion
occurs in the late distal and cortical collecting tubules, where
potassium can be either reabsorbed or secreted, depending on the
needs of the body.
B.P.U.M.S

Pourkhalili
145
Potassium secretion by principal cells
B.P.U.M.S

Pourkhalili
146
Intercalated cells reabsorb k during potassium depletion
B.P.U.M.S

Pourkhalili
147
Factors that regulate k secretion by principal cells
 Plasma potassium concentration
 Aldosterone
 Tubular flow rate
 Hydrogen ion concentration
B.P.U.M.S

Pourkhalili
148
1. Increased ECF K concentration stimulates potassium
secretion by 3 mechanisms:
a. Increased ECF K concentration stimulates the Na-K ATPase pump,
thereby increasing K uptake across the basolateral membrane.
b. Increased ECF K concentration increases the K gradient from the renal
interstitial fluid to the interior of the epithelial cell; this reduces
backleakage of potassium ions from inside the cells through the
basolateral membrane.
c. Increased K concentration stimulates aldosterone secretion, which further
stimulates potassium secretion
B.P.U.M.S

Pourkhalili
149
B.P.U.M.S

Pourkhalili
150
2. Aldosterone stimulates potassium secretion by
principal cells
B.P.U.M.S

Pourkhalili
151
 Increased extracellular potassium concentration
stimulates aldosterone secretion
B.P.U.M.S

Pourkhalili
152
 Increased plasma k concentration directly and indirectly
raises k secretion
B.P.U.M.S

Pourkhalili
153
 Blockade of aldosterone feedback system greatly
impairs control of potassium concentration
B.P.U.M.S

Pourkhalili
154
3. Increased distal tubular flow rate stimulates potassium
secretion.
 A rise in distal tubular flow rate, as occurs with:
 Volume expansion
 High sodium intake
 Diuretic drug treatment
 Conversely, a decrease in distal tubular flow rate, as
caused by sodium depletion reduces potassium
secretion.
B.P.U.M.S

Pourkhalili
155
B.P.U.M.S

Pourkhalili
156
4. Acute acidosis decreases potassium secretion
 The primary mechanism by which increased hydrogen
ion concentration inhibits potassium secretion is:
 Decreased activity of the Na-K ATPase pump. This in turn decreases
intracellular potassium concentration and subsequent passive diffusion of
potassium across the luminal membrane into the tubule.
B.P.U.M.S

Pourkhalili
157
 Chronic acidosis, lasting over a period of several days,
increases urinary potassium excretion.
 The mechanism for this effect is:
 Chronic acidosis inhibit proximal tubular sodium chloride and water
reabsorption, which increases distal volume delivery, thereby stimulating the
secretion of potassium.
 This effect overrides the inhibitory effect of hydrogen
ions on the Na-K ATPase pump. Thus, chronic acidosis
leads to a loss of potassium, whereas acute acidosis
leads to decreased potassium excretion
B.P.U.M.S

Pourkhalili
158
B.P.U.M.S

Pourkhalili
159
Micturition reflex
B.P.U.M.S
Physiologic anatomy and nervous connections of the
bladder

Pourkhalili
160
Filling of the bladder and cystometrogram
B.P.U.M.S

Renal physiology bpums

Recomendados

Recomendados

Más contenido relacionado

La actualidad más candente

La actualidad más candente (20)

Destacado

Destacado (20)

Similar a Renal physiology bpums

Similar a Renal physiology bpums (20)

Último

Último (20)

Renal physiology bpums

Notas del editor