urinary 3
TRANSCRIPT
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Wang Guoqing
Department of Physiology,
Medical School, Soochow University,
Suzhou 215123, ChinaE-mail:[email protected]
Tel:0512-62096158; 13506212030
Chapter 8Formation and Excretion of Urine
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Chapter outline
I. Functional renal anatomy
II. Renal blood flow
III. Glomerular filtration
IV. Transport in the renal tubule and collecting duct
V. Urinary concentration and dilution
VI. Regulation of urine formation
VII. Clearance
VIII.Renal regulation of acid-base balance
IX. Micturition
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Respiratory system ( )Large intestine ( )
Skin ( )
Kidney ( )**
Excretion pathway
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Excretory Approach
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Urinary System
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General principles
Kidney Functions**
Kidneys regulate water and electrolyte levels.
Kidneys regulate acid-base balance.
Kidneys excrete metabolic waste products and foreign
substances.
Hormones produced are angiotensin ,1, 25-
dihydroxyvitamin D3, aldosterone and
erythropoietin(EPO).
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Body water homeostasis (balance)
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I. Functional renal anatomy
The nephron is the basic subunit of the kidney. It iscomposed of two components: the glomerulus and therenal tubule.
Renal arterioles lead to glomerular capillary tufts, which
are the site of blood filtration. Bowmans capsule receives this filtrate, which is modified
as it passes along the kidney tubules.
A single kidney is divided into four major sequential
sections:Proximal tubule, loop of Henle, distal tubule, and collectingduct, each with unique characteristics.
Capillaries surround kidney tubules enabling exchangebetween blood and tubular fluid.
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1.Basic kidney structure
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Renal Tubules
2. Nephron structure
Nephron is composed of two components: the glomerulus and the renal tubule.
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Nephron structure
Nephron is composed of two components:
the glomerulus and the renal tubule.
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Nephrons can reach to
renal medulla
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Cortical nephron The nephrons have their glomeruli located in theouter and middle portion of the renal cortex arecalled cortical nephrons.
Juxtamedullary nephron
The nephrons have glomeruli that lie deep in therenal cortex near the medulla and have long
loops of Henle that are deep into the medullaare called juxtamedullary nephron.
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Cortical Nephron Juxtamedullary Nephron
85% 15%
A
A
U
N
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3. Glomerulus
Called Capillary Tufts
Under the Electronic
Microscope
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Glomerulus
Blood In
Blood Out
Relationship visualized as a fist(Glomerulus,in) and a balloon(Bowman`s capsule, out)
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juxtaglomerular apparatus
The juxtaglomerular apparatus consists ofthe juxtaglomerular cells, the macula
densa and the extraglomerular mesangial.
juxtaglomerular cell
The juxtaglomerular cells are specializedmyoepithelial cells in the media of afferentarteriole close to the glomerulus.
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Juxtaglomerular apparatus JG cells can secrete Renin.
JG cells serve as baroreceptor in afferent arteriole.
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4. Glomerular filtration membrane
porous
he epithelial cellsof Bowman`scapsule called
Space
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Glomerular filtration membrane
The barrier between the capillary bloodand the fluid inside the Bowmen's capsule
is called glomerular filtration membrane.
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Glomerular filtration membrane
Pores
Glomerular filtration membrane isimpermeable to blood cell and plasmaprotein.
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5. Renal tubule
The renal tubule is divided intofour sections: proximal tubule,loop of Henle, distal tubuleandcollecting duct.
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Nephron
Collectingduct
Glomerulus
Bowman capsule
renalcorpuscle
renal tubule
proximaltubule
henle loop
distal tubule
proximalconvoluted
tubule
distalconvoluted
tubule
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II. Renal blood flow (RBF)Renal blood flow distribution
95%
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Renal blood flow (RBF)
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Renal blood flow distribution
1 A d ill t k
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1. A second capillary networks
called the peritubular capillaries
a first capillarynetwork
a second capillarynetwork
These capillaries surround specific
segments of the tubule, and theyreturn water and substancesreabsorbed by the tubule to thegeneral circulation, as well as deliverneeded nutrients to the tubule.
P it b l ill i
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Peritubular capillariesUnder the electronic microscope
Higher plasma colloid osmotic pressure in the peritubularcapillaries is in favor of tubular reabsorption.
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2. vasa recta
3 Ch i i f l bl d fl **
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3. Characteristics of renal blood flow**
Large blood flow400 ml/min100g
Maldistribution of blood flow
renal papilla (1%) renal medulla (5%)renal cortex (94%)
Primary and secondary capillary networks
glomerular capillary network (primary network)
(between afferent glomerular arteriole and efferent glomerular arteriole,
high blood pressurein favour of glomerular filtration)
peritubular capillary network (secondary network)
(made by branch of efferent glomerular arteriole, low blood pressure, in
favour of tubular reabsorption)
Autoregulation of renal blood flow Tubuloglomerular feedback
Nervous and humoral regulation
Renal blood volume
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4. Determinants and regulation of RBF
RBF is determined by systemic arterial bloodpressure and renal vascular resistance (renalsympathetic vasoconstrictor nerve control).
RBF demonstrates autoregulation. Autoregulation involves afferent not efferent
arterioles.
Autoregulation is explained either by themyogenic hypothesis or tubuloglomerularfeedback.
A t l ti f RBF d GFR
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Autoregulation of RBF and GFR
Systemic Arterial Pressure (mm Hg)80 150
Glomerular Filtration Rate
Renal Blood Flow (RBF)
Ren
alBloodFlow
orGlomerular
Filtration
Rate
The kidney maintains a constant blood flow (autoregulation) andglomerular filtration rate over the physiological range of systemicarterial pressure.
Autoregulation means simply regulation of blood flow bythe tissue itself. Whenever on excessive amount of blood
flows through a tissue., the local vasculture constricts anddecreases the blood flow forward to normal.
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Autoregulation of RBF and GFR
Mechanism of autoregulation
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Mechanism of autoregulationTwo hypotheses describe autoregulation:
myogenic and tubuloglomerular feedback.
1.The myogenic hypothesis: When systemic arterial pressure
increases RBF, the afferent arterioles are stretched. This stretchstimulates them to contract increasing their resistance and maintaininga constant RBF. If RBF decreased, then the opposite would occur.
2. Tubuloglomerular feedbackinvolves an interaction between thedistal tubules and the afferent arterioles. The beginning portion of the
distal tubule passes close to the afferent arteriole, and together theyform a specialized structure called thejuxtaglomerular apparatus.Specialized epithelial cells in this portion of the distal tubule, calledmacula densa cells, sense the amount of NaCl (sodium chloride) in thetubular fluid. With an increase in RBF there will be an increase in GFR,
an increase in filtration, and an increase in the amount of NaCl passingby the macula densa cells. In response to this increased NaCl, a yetunidentified substance is released that causes afferent arteriolarconstriction. This constriction reduces RBF, GFR, and the amount ofNaCl delivered to the macula densa cells. If RBF were to decrease, then
the opposite would occur.
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Tubuloglomerular feedback
NaCl
NaCl
5 N i ti f kid
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5. Nerve innervation of kidney
Renal sympathetic vasoconstrictor nerve
control the smooth muscle of afferent glomerular arterioleand efferent glomerular arteriole, renal tubule andjuxtaglomerular cell. Vasoconstriction and RBF regulation Increased reabsorption of Na+ Cl-, etc., in the renal
tubular epithelial cell control juxtaglomerular cell to release renin
Kidney have no vagus nerve fibers innervation
Renal afferent nerve fibers act on mechanical andchemical stimulation toward central nervous system.
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,,.
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Process of urine formation
Three steps:Glomerular filtration
Renal tubule/collecting duct
reabsorptionRenal tubule/collecting ductsecretion and excretion
Material transport of renaltubule/collecting duct
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III. Glomerular filtration
Glomerular filtration rate (GFR)
Effective filtration pressure (EFP)
Factors affecting glomerular filtration rate
Regulation of GFR
Interaction between renal blood flow (RBF)and GFR
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Basic renal terminology * Glomerular filtration rate (GFR) is the amount of fluid
moving into Bowmans capsule per unit time (min). Renal blood flow (RBF) is the amount of blood flowing
through the kidney per unit of time (min). Filtration is the process by which substances enter
Bowmans capsule.
Reabsorption is the process by which substances movefrom inside to outside the tubule.
Secretion is the process by which substances move fromoutside to inside the tubule.
Excretion refers to substances that pass from the kidneyinto the bladder.
it is the ability of the kidney to selectively move specificsubstances into and out of the tubule in a very controlledand coordinated manner that makes normal kidneyfunction so critical to life.
E l i f
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Explanation for some terms
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Glomerular filtration*Filtration is the process by which substances enter
Bowmans capsule.
Glomerular filtration rate, GFR* ( )
It is the amount of fluid moving into Bowmans capsule per
unit time (min).
glomerular filtration fraction, GFF* ( )
The glomerular filtration fraction is the filtration rate aspercentage of the total renal plasma flow that passes
through both kidneys.
1. Glomerular filtration rate (GFR)
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2. Factors affecting glomerular filtration rate
Effective filtration pressure
Filtration coefficient Kf
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(1) Glomerular effective filtration pressure
The effective filtration pressure of glomerulus
represents the sum of the hydrostatic andcolloid osmotic forces that either favor or
oppose filtration across the glomerular
capillaries.
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Effective
filtration pressure Glomerular
capillary pressure Plasma colloid
osmotic pressure
intracapsular
pressure
Formula*:
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(2) Filtration coefficient Kf
Under the effective filtration pressure (EFP) driving
force, liquid volume passing through filtration
membranes per unit time.
Two determinants ofKf
filtration membranes area (s)
permeability coefficient of filtration membranes (K)Kf = k s
St t f filt ti b
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Structure of filtration membrane
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3. Factors affecting glomerular filtration**
Change of effective filtration pressure
Change of filtration coefficient
GFR KfS PGCGCPBC
GFR: glomerular filtration rate S: glomerular filtration membrane area
Kf : permeability coefficient PGC: glomerular capillary pressure
GC: plasma colloid osmotic pressure PBC: hydrostatic pressure in bowman
Changes in renal blood flow
EFP
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GFR is determined by the balance of forces acting across thefiltration membrane. The forces that drive fluid out of theglomerulus are the capillary blood pressure (PGC) and theosmotic pressure (BC) of the fluid in Bowmans capsule. The
forces driving fluid into the glomerulus are the hydrostatic
pressure (PBC) of the fluid in Bowmans capsule and theosmotic pressure (GC) of the blood within the glomerulus.The difference between these four forces determines the netfiltration pressure, which is approximately 15 mm Hg.
Net filtration pressure* = (PGC+BC) (PBC+GC)= (55+0) (15+25) = 15 mm Hg
BCis zero. Explanation
Filtration coefficient(Kf), a factor reflects permeability of
filtration membrane.
Determinants and regulation of GFR and RBF
N t filtr ti n pr ssur
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Net filtration pressure
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4. Regulation of GFR Changes in systemic arterial pressure, the radius of the
renal arterioles, and the filtration coefficient normallyregulate GFR.1. If systemic arterial pressure increases, then the pressurein the glomerular capillaries will increase and GFR willincrease. The opposite will happen if systemic arterialpressure decreases.2. Renal arteriolar resistance. (see next illustration)3. Filtration coefficientThe filtration coefficient can bealtered by the contractile activity of an additional set ofcells located among the podocytes. These cells are calledmesangial cells. These cells can be stimulated to contract,and when this occurs they decrease the area available forfiltration and thus decrease the filtration coefficient andGFR.4. Clinic diseases:
Starvation / Burn GFR,Renal Stones GFR
5 Interaction between RBF and GFR
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5. Interaction between RBF and GFRAs discussed above, an increase in efferentarteriolar resistance produces opposite effects on
RBF and GFR. RBF decreases and GFR increases.Under normal situations, blood leaving theglomerular capillary bed is at a higher osmoticpressure (GC) than the blood entering because of
the fluid lost as ultrafiltrate. This rise in GC is notsufficient to significantly limit GFR.
However, with a large increase in efferent resistance,RBF is reduced enabling GC to increase to such anextent that GFR is reduced. Therefore, GFR does notincrease as much as expected with an increase inefferent arteriolar resistance because of therelationship between GFR, RBF, and GC.
R l i f GFR i h diff
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Regulation of GFR with differentarteriolar diameters
PGCPGC
PGC
Decreased Afferent
Arteriolar Diameter GFR Glomerular Capillary
GFR
Decreased Efferent
Arteriolar Diameter
Changes in arteriolar resistance before (afferent) and after (efferent) theglomerular capillary bed have different effects on capillary hydrostatic
pressure (PGC) and therefore on glomerular filtration rate (GFR).
Effects of different arteriolar
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Effects of different arteriolarresistance on GFR
Effects of different arteriolar
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Effects of different arteriolarresistance on GFR
Effects of different arteriolar
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Effects of different arteriolarresistance on GFR
Effects of different arteriolar
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Effects of different arteriolarresistance on GFR
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Nervous and humoral regulation of RBF and GFR
Nervous regulation Renal sympathetic nerve:
Hypovolemia, noxious stimulation or agitation, etc.sympatheticnervous activity afferent glomerular arteriolecontraction
RBF and GFRHypervolaemiasympathetic nervous activity afferent
glomerular arteriole dilatation RBF and GFR .
Humoral regulation
epinephrine, norepinephrine, vasopressin, angiotensin
Renal vasoconstriction decreases RBF.
prostaglandin, NO, ANP, bradykinin, endothelin
Renal vasodilatation increases RBF.
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Summarization
PLEASE TAKE DOWN
Summary
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Summary Urine formation starts with the filtration of plasma in
the kidney. Glomerular filtration is favored by the high hydrostatic
pressure of the blood in the glomerular capillaries and
is opposed by the hydrostatic pressure in the urinary
space of Bowmans capsule and by the glomerular
capillary colloid osmotic pressure.
Glomerular filtration is rather nonselective; proteins
are mostly retained in the plasma by the glomerularbarrier, but all low-molecular-weight substances are
freely filtered.
Key terms: GFR, EFP, FF, Autoregulation
IV. Transport in the renal tubule
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1. Overview of tubule properties Permeability properties of the luminal and basolateral
membranes of the epithelial cells lining renal tubules aredifferent, enabling directional movement of salt and
water. Proximal tubule reabsorbs isotonically a constant 60%
of the GFR.
Loop of Henle reabsorbs more salt than water.
Distal tubule continues to reabsorb more salt than water. Permeability of the collecting duct to salt and water is
hormonally controlled by antidiuretic hormone (ADH)and aldosterone. [dilute urine / concentrated urine]
IV. ransport n the renal tubuleand collecting duct
R b ti d ti i th l
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Reabsorption and secretion in the renaltubule and collecting duct
Transport
Renal tubular reabsorption* ( )
Tubular reabsorption denotes the transport of substancesfrom the tubular fluid through the tubular epithelium into
peritubular capillary blood.
Secretion of the renal tubule and collecting duct
(
Product made by epithelial cells itself or blood
substance are transported into renal tubular lumen.
Definition
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Transport patterns
assive transportdiffusion, permeation, facilitate diffusion, solvent
daggling
Active transport
sodium pump, hydrogen pump, calcium pump (symportor antiport)
Transport pathway:
Paracellular pathway transcellular pathway
2. Reabsorption of the renal tubule and
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pcollecting duct
Proximal tubule reabsorbs 67%of the filtered Na+, Cl-
and H2O
Proximal tubule is the only site for glucose reabsorption
Loop of Henle reabsorbs 20% of the filtered Na+ and Cl-
The luminal cell membrane of the thick ascending limb
contains a Na+-k+-2Cl- cotransporter
The distal tubule and collecting duct reabsorb 12% of thefiltered Na+ and Cl-
General situation
Renal tubule reabsorption of
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Renal tubule reabsorption of
salt and water
3 Proximal tubule reabsorption of
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3. Proximal tubule reabsorption ofsalt and water
NaCl reabsorption is dependent upon the coordinated
action of the Na-K-ATPase on basolateral membrane
of the epithelial cell and several facilitated transport
systems on the luminal membrane of the epithelial cell.
Water reabsorption follows and is dependent upon Na
ion reabsorption.
Water reabsorption is assisted by the elevated
osmolarity of the peritubular capillary blood.
Proximal tubule reabsorption of salt
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and water
The major mechanisms by which molecules move across the epitheliumof the proximal tubule are diagramed in this figure.
ATP
Na+
Na+
K+Na+
Glucose & amino acids
H+
Water
Luminal membraneBasal lateralmembrane
Proximal Tubular Cell
BLOOD
TUBULARFLUID
Cell 1
Cell 2
P i l b l b i f N
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Proximal tubule reabsorption of Na+
Proximal tubule reabsorption
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of salt and water
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4. Proximal tubule reabsorption of
glucose and amino acids
Reabsorption of glucose and amino acids iscoupled to the reabsorption of Na ions.
Glucose reabsorption is overwhelmed whenblood glucose is very high (diabetes).
[daiebi:ti:z, -ti:s]
Proximal tubule reabsorption
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of glucose
Proximal tubule reabsorption
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of glucose
Relationship between plasma glucosed fil i f l
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and filtration rate of glucose
Relationship between plasma glucose
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and reabsorption rate of glucose
Relationship between Plasma Glucosed E ti R t f Gl
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and Excretion Rate of Glucose
renal glucose threshold*When the plasma glucose concentration increasesup to a value about 180 to 200 mg per deciliter,glucose can first be detected in the urine, this valueis called the renal glucose threshold.
Summary about Glucose
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Summary about Glucose
Graph Questions
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Graph Questions
5. Proximal tubule reabsorption
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pof bicarbonate ions
Bicarbonate reabsorption requires Na-
dependent H ion secretion.
Bicarbonate reabsorption occurs
indirectly through the formation of CO2
and H2
O.
Proximal tubule reabsorption
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TUBULAR
FLUID
BLOO
D
Na+
H+ +HCO3-
H2CO3
CO2 + H2OH2O + CO2
H2CO3
HCO3- + H+
CACA
Na+ + HCO3-
Reabsorption of bicarbonate ions in proximal tubule requires the formationand breakdown of carbonic acid (H2CO3) within the tubular fluid and epithelialcells. The enzyme carbonic anhydrase (CA) is essential for this process tooccur.
Some diuretics work by inhibiting the carbonic anhydrase enzyme.
Proximal tubule reabsorptionof bicarbonate ions
Proximal tubule reabsorptionf bi b t i
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of bicarbonate ions
6. Loop of Henle reabsorption of
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6. Loop of Henle reabsorption ofsalt and water
Descending limb of the loop of Henle is
permeable to water but not to salt.
Ascending limb of the loop of Henle is
permeable to salt, because of a Na-K-Cl ion
tritransporter, but not to water.
Reabsorption of water from the descending limb
results from the reabsorption of salt by thetritransporter in the ascending limb.
Loop of Henle reabsorption ofsalt and water
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salt and water
Ascending limb of the loop of Henle: a Na-K-Cl ion
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tritransporter for reabsorption of salt
Blood
Na+-2Cl--K+
tritransporter
TubularLumenFluid
Place is the ascending limb of the loop of Henle
CELL
Tubule epithelial Cell
C t t lti li ti
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Counter-current multiplication
An osmotic gradient is established in the interstitialspace surrounding the loop of Henle that increases
from the top to the bottom of the loop.
The action of the tritransporter of the epithelial cells
of the ascending limb, the water permeability of the
descending limb, and the shape of the loop
contribute to the development of this osmotic
gradient.
The process by which this occurs is called counter-
current multiplication.
Counter current dissipation
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Counter-current dissipation
Counter-current exchange
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g
Counter-current multiplication
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A B
C D
300
300
300
300
300
300
300
300
300
300
300
300
Water
Reabsorption
Na-K-Cl
Reabsorption
400400
400
400
400
400400
400
400
400
200200
200
200
200
Equilibrium State
300
300
400
400
400
400
400
400
400
200
200
400
400
400
Equilibrium State
350
350
350
500
500
350
350
350
500
500
150
150150
150
300
300
Increasing
Osmotic GradientThe shape and permeability properties of the loop of Henle enable an osmotic gradient to be established
within the kidney. Diagrams A through D show in a step-wise manner how the gradient is established.
pAssuming that initially all fluid within theloop has the same osmolarity (panel A) thetritransporter will reabsorb Na, K, and Clfrom the tubular fluid creating an osmotic
gradient of 200 mOsm between the interstitialspace and the tubular fluid. The ascendinglimb is not permeable to water so watercannot follow. The descending limb is notpermeable to salt so it cannot enter from theinterstitial space. However, the descendinglimb is permeable to water so water isreabsorbed into the interstitial space. A newsteady state is established (panel B). At this
point new fluid enters from the proximaltubule displacing the fluid within the loop.This disrupts the steady state (panelC).Through the reabsorption of salt by theascending limb and water by the descendinglimb, a new steady state is established (panelD). Notice that an osmotic gradient is beingestablished in the interstitial space from thetop to the bottom of the loop. It is the result
of the loop structure and the differentpermeabilities of the two limbs of the loop.Fluid leaving the ascending limb is hypotoniccompared to the fluid entering because moresalt than water is reabsorbed. We will see ina later section that the interstitial osmoticgradient is critical for water reabsorption.
Counter-current exchangeof vasa recta
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of vasa recta
7. Distal tubule reabsorption oflt d t
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salt and water
More salt than water is reabsorbed.
Na and Cl ions reabsorbed together.
The distal tubule retains some of the properties ofthe ascending limb of the loop of Henle in that it is
not very permeable to water and reabsorbs Na andCl ions. The reabsorption of Na and Cl ions occursthrough a co-transport carrier protein on theluminal side of the epithelial cell that combines the
movement of one Na and Cl ion into the cell. Thisreabsorption is driven by the Na ion concentrationgradient established by the Na-K-ATPase on thebasal lateral side of the epithelial cell.
Distal tubule reabsorption of
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BloodTubularFluid
Lumen
psalt and water
Tubule epithelial Cell
Tubule epithelial Cell
Tubule epithelial Cell
Symporter
8. Collecting duct reabsorptionf lt d t
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of salt and water
The permeability of the collecting duct to Naions and water is variable.
Antidiuretic hormone (ADH or Vasopressin,
VP) increases the permeability of thecollecting duct to water.
Aldosterone increases the reabsorption of Na
ions by the collecting duct.
Collecting duct reabsorption
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Epithelial Cell of the Collecting Duct
TubularLumenFluid
Blood
Epithelial Cell of the Collecting Duct
of Na+
Effect of antidiuretic hormone (ADH) on thepermeability of the collecting duct to water
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permeability of the collecting duct to waterADH release
Concentrated Urine
EpithelialCellofthe
Collecting
Duct
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Antidiuretic Hormone(ADH i VP)
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(ADH or vasopressin, VP)
Mechanism of ADH or VP in thell ti d t f t b ti
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collecting duct for water reabsorption
Antidiuretic hormone, also known as vasopressin, a posterior pituitaryhormone, increases the number of aquaporin channels in the membraneof the epithelial cells increasing water reabsorption. In the presence ofADH, water can leave the collecting duct in response to the osmotic
gradient.
Relationship between plasmaosmolarit and plasma asopressin
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osmolarity and plasma vasopressin
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9. Collecting duct secretion of Kd H i
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and H ions The collecting duct secretes both K and H ions.
K and H ion secretion is sensitive to aldosterone.
K ions are secreted through channels located in theluminal membrane of specialized epithelial cells of thecollecting duct called principle cells. This secretion isdown a concentration gradient established by the Na-K-ATPase located on the basolateral membrane. In thepresence of aldosterone, more channels are opened andsecretion is increased.
Specialized cells of the collecting duct, called intercalatedcells, are responsible for H ion secretion. This secretion isdue to an active transport process that moves H ions fromthe inside of epithelial cell to the tubular fluid. The activity
of this transporter is increased by aldosterone.
Collecting duct secretion of Kand H ions
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and H ions
Cl-
TubularLumen
Fluid
Blood
principle cell
Channels
aldosterone+
intercalated cell
Epithelium of the Collecting Duct
Epithelium of the Collecting Duct
aldosterone+
10. NH3secretion is related to H+and HCO3
-
t t
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transport
60% of NH3 secretion
from glutaminate (
), 40%from glycine
( )
secretion promotes
secretion and
reabsorption, in favor
of renal acids excretion
and alkaline
reabsorption.
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NH3NH3
NH4
V. Urinary concentration
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and dilution
Urinary dilution
Urinary concentration
The loops of Henle are countercurrentmultipliers
The vasa recta are countercurrent exchangers
Urea plays a special role in the concentratingmechanism
1. Overview
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urinary concentration
The basic requirements for forming a concentrated urine
are a high level of ADH and a high osmolarity of the
renal medullary interstitial fluid.
urinary dilution
The mechanism for forming a dilute urine is continuously
reabsorbing solutes from the distal segments of the
tabular system while failing to reabsorb water.
Urinary concentration and dilution2
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2. Definition
Plasma osmotic pressure (POP) 300 mmol/L300mOsm/kg H2O
Urine osmotic pressure POP, hypertonic urine
Concentrated urine, 1200 mmol/L Urine osmotic pressure POP, hypotonic urine
Diluted urine, 50 mmol/L
Urine osmotic pressure =POP, isosthenuria
Urinary concentration and dilution of kidneyis damaged.
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3. Mechanism of urinary concentration and dilution
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3. Mechanism of urinary concentration and dilution
Uinary dilution
Na+Cl-
ADH
Na+
Urinary concentration
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Urinary concentration
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4
Forming mechanisms of hypertonicity in the medulla
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Countercurrent multiplication of Henle's loop
Countercurrent exchange of vasa recta
Counter-current theory
U
vasa recta
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Countercurrent multiplication Countercurrent multiplication is the
process where by a small gradient
established at any level of the loop ofHenle is increased (multiplied) into a much
larger gradient along the axis of the loop.
Countercurrent multiplicationof Henle's loop
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:
NaClNaCl
NaCl
urea recycling
NaCl
NaClurea
Countercurrent exchange of vasa recta
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NaCl
Process of urinary concentration and dilution
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VI. Regulation of urine formation
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VI.Regulation of urine formation
Autoregulation of urinary formation
Glomerulotubular banlance
Effect of renal sympathetic nerve
Effect of antidiuretic hormone
Renin-angiotensin-aldosterone system
Effect of atrial natriuretic peptide
1. Regulatory patterns and Significance
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g y p g
Regulatory patterns:
Autoregulation ( )
Nervous regulation ( )
Humoral regulation ( )
Significance
Maintenance of internal environmenthomeostasis.
2. Autoregulation in kidney
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g y osmotic diuresis
Solute concentration of renal tubular fluid Mannitol ( ) clinic use
Different from water diuresis *
Glomerulotubular balance
One of the most basic mechanisms for controlling
tubular reabsorption is the intrinsic ability of the tubules
to increase their reabsorption rate in response toincreased tubular inflow. This phenomenon is referred to
as glomerular-tubular balance.
The volume of urine increases when water intake
exceeds body needs, it is resulted from suppression ofADH secretion.
3. Nervous regulation
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Renal sympathetic nerve
receptor activation contracts afferent and efferentglomerular arteriole inducing decreased RBF and GFR .
receptor activation increases proximal convoluted tubule
reabsorbing Na+ and othersolutes;
receptor activation promotes juxtaglomerular cellreleasing renin;
Homeostasis of Na+and water maintained.
Renal sympathetic nerve involved in reflex:
cardiopulmonary receptor reflex; Kidney Kidney reflex.
4. Humoral regulation
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Renin-angiotensin-aldosterone system RAAS
- - Renal kallikrein-kinin system ( - )
Atrial natriuretic peptide ANP
Endothelin ET
Nitric oxide NO
Vasopressin VP
Antidiuretic hormone ADH
Catecholamine, CA
Prostaglandin, PG ( )
Renalregulation of salt andt b l
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water balance
Sensing alterations in salt balance Salt balance, principally NaCl concentration, is
assessed by monitoring osmolarity.
Salt levels are changed by adjusting waterreabsorption through the action of antidiuretichormone (ADH).
ADH* increases the number of open aquaporinchannels in the collecting duct therebyincreasing water reabsorption.
Renal regulation of salt andwater balance
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Cells shrink
[NaCl]o
Signal to
water balance
Sensing alterations in waterbalance
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balance
Water balance is assessed by monitoring bloodvolume through changes in blood pressure.
Water levels are changed by adjusting saltreabsorption through the renin-angiotensin- -aldosterone system.
Increased sympathetic nerve stimulation directlyincreases renal secretion of renin.
Decreased distal tubule Na-load directly stimulatesrenal renin secretion.
Increased volume stimulates the secretion of atrialnatriuretic peptide form the atria.
Sensing alterations in waterbalance
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a ance
Sensing alterations in water balance
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g
Renin-Angiotensin- -Aldosteronesystem (R-A-A-S)
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system (R A A S).
Increased sympathetic nerve stimulation directly increasesrenal secretion of renin.
+
Angiotensin- also directly stimulates Na+
reabsorption by cells of the proximal tubule.
-
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Effects of ANP on kidney
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Dilatation of afferent glomerular arteriole increases GFR and
Na+ in tubular fluid;
Inhibiting Na+ channel on the collecting duct epithelium with
help of cGMP decreases Na+ and waterreabsorption at the
collecting duct;
Inhibiting renin release reduces ANG and aldosterone
secretion, then indirectly inhibits Na+ reabsorption
Inhibiting ADH secretion induces kidney water drain
increasingly.
Sensing alterations in water balance
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Renal regulation of salt and water balanceRelationship of osmolarity and volume
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p y
5. Reflex response to dehydration*D h d ti lt f i b l b t t
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Dehydration initiates reflexes to conserve bothsalt and water .
Dehydration reduces blood pressure , which
reduces GFR and RBF independent of otherfactors.
Baroreceptor-regulated increased sympathetic
nerve activity activates the renin-angiotensin- -aldosterone system and decreases GFR and RBF.
Osmoreceptors stimulate the release of ADH.
Sense of thirst is stimulated.
Dehydration results from an imbalance between waterintake and water loss
Reflex response to dehydration *
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With sweating (running) induced dehydrationwater volumeand
osmolarityblood pressureGFR,RBFwater and salt excretion
Blood pressurebaroreceptormediated reflex responsesympathetic nerve activityR-A-A-Swater and salt
reabsorptiondiminish dehydration
Sympathetic nerve activityafferent arteriolar constriction
GFR,RBF diminish dehydration
Blood pressureGFR and the distal tubule Na loadThe distal
tubular epithelial cells stimulatereninR-A-A-S
Extracellular osmolarityADH releasewater reabsorption
Water volumeand osmolaritythirst occursdrink water
Na+
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RSSA
RSSA
Na+
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VII. Renal clearanceResearch method of kidney function
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Research method of kidney function
Renal clearance **
The volume of plasma per unit time
needed to supply its quantity of substanceexcreted in the urine per unit time.
Clearance*
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Clearance used to measure GFR and RBF Clearance is based on the principle of
conservation of mass.
Clearance is the volume of blood per unit of timethat had all of a particular substance removed bythe kidney.
The clearance formula is Cx= (VU [X]U) / [X]p The clearance of substances with specific
properties enables one to determine GFR and RBF.
Clearance for use
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1 g/mL Glomerular Capillary Efferent Arteriole
Afferent Arteriole
125 mL/min
125 g/min
Proximal Tubule
1 mL/min
125 g/mL
125 g/min
Bowman`sCapsule
PeritubularCapillary
Urine
This figure illustrates the principle ofclearance and how it can be used todetermine glomerular filtration rate.
Clearance = GFR
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Creatinine, that is normally present in the bloodand is not reabsorbed and minimally secreted
by the kidney. By measuring urine flow rate and
the concentration of creatinine in the blood andurine, the GFR can be calculated. Because of
the characteristics of creatinine, you can say
that the clearance of creatinine is the GFR. The clearance equation: Cx= (VU[X]U) / [X]p
Urea clearance
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Glucose clearance
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Penicillin clearance
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Clearance for use
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The clearance equation can also be used tocalculate renal plasma flow(RPF) if asubstance with an additional property is used.This additional property is that all of it needs tobe removed from the blood by the kidneythrough a combination offiltration and secretion.
Para-aminohippuric acid (PAH) clearance
equals the RPF. RBF= RPF/ (1 - Hct). (hematocrit, Hct)
Significance of renal clearance
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Estimate renal function; Determine glomerular filtration rate (GFR )
Determine renal blood flow (RBF)
Presume renal tubular transport effect
Free-water clearance
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Efferent arteriole
Afferent arterioleDistal convoluted tubule
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Bowmancapsule
Glomerulus
micropuncture
VIII. Renal regulation of acid-basebalance
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balance
General considerations Metabolism of food generates acid.
Acid in the body is in two forms: fixed and
volatile. Kidneys remove excess fixed acid; lungs
remove excess volatile acid.
Acidemia is excess H ions in the blood;alkalemia is excess bicarbonate ions in theblood.
Normal Blood pH Value 7 35 7 45
Renal regulation of acid-basebalance
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Normal Blood pH Value 7.35 7.45
CO2 + H2O H2CO3 H+ + HCO3
-, H+ is volatile acid
Increasing ventilation will blow off more CO2 driving the reactionto the left and lowering the H+ concentration.
Decreasing ventilation will allow CO2 to accumulate driving thereaction to the right and increasing the H+ concentration.
Other acids named fixed acids. (such as sulfuric and phosphoricacids ).
Kidneys role (keeps appropriate level of bicarbonate ions /excretes the fixed acids produced by the body / secreteshydrogen ions).
Lungs role (ventilation controls CO2 adjusting [H+
] ). When the blood contains excess H ions the condition is called
acidemia (acidosis ). Diarrhea
When the blood contains excess bicarbonate ion, the conditionis called alkalemia (alkalosis). Vomiting
Renal regulation of acid-base balance
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Renal production of bicarbonate ions
The kidney produces bicarbonate through the
formation of titratable acid. The kidney produces bicarbonate through the
metabolism of glutamine.
Renal production of bicarbonate ions
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Formation of titratable acid in the proximal tubule is one way by which the kidneygenerates new bicarbonate ions in response to acidemia. The H+ ion secreted bythe epithelium is excreted as NaH2PO4 (titratable acid) leaving a bicarbonate ionbehind.
Na+
Na++NaHPO4-
Na2
HPO4
H+ H++ NaHPO4-
NaH2PO4
Urine
Renal TubularEpithelial Cell
TUBULA
RFLUID
(Disodium salts)
(Monosodium salts)Carbonic acid
(H2CO3)
HCO3- + H-
BLOOD
H+
Glutamine NH3 NH3+H+
Renal production of bicarbonate ions
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Renal production of bicarbonate ions
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Epithelium of the Collecting Duct
Epithelium of the Collecting Duct
(New HCO3- )
TubularLumen Fluid
Blood
Renal production of bicarbonate ions
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Renal secretion of H ionsTubularLumen
BloodEpithelium of the Collecting Duct
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H ion secretion in the collecting duct leads to acidification of the urine.
Collecting duct H ion secretion is stimulated by aldosterone.
Cl-
LumenFluid
principle cell
Channels
aldosterone+
intercalated cell
Epithelium of the Collecting Duct
aldosterone+
Pump
[H+]=4 10-8 M
pH=7.4
[H+]=3 10-5 M
pH=4.5
Renal compensation foralkalemia
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When the blood contains excess base, the kidneyexcretes bicarbonate and does not generateadditional bicarbonate. Increase bicarbonateexcretion occurs because there are insufficient H
ions to be secreted by the proximal tubules toreabsorb all the filtered bicarbonate. The excessbicarbonate is excreted. Also, the low level of Hions means that filtered sulfuric and phosphoric
acids will not be titrated and so no additionalbicarbonate will be generated. In these ways, thekidney attempts to lower the blood bicarbonateconcentration compensating for the alkalemia.
Renal compensation for alkalemia
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Renal compensation foracidemia
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When the blood contains excess H ions, the kidneyexcretes H ions and generates additional bicarbonate. Inthe presence of excess H ions, there are plenty of H ions toreabsorb all the filtered bicarbonate. In addition, the filtered
fixed acid will be titrated generating additional bicarbonateions. Also, the excess H ions stimulate the metabolism ofglutamine by the kidney and the production of even morebicarbonate. Finally, the collecting duct increases itssecretion of H ions. The combined effects of complete
bicarbonate reabsorption , new bicarbonate generation,and the secretion of H ions helps the body compensate forthe acidosis.
Renal compensation for acidemia
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concentration
Relationship Between plasma K IonConcentration and Acid-base Status
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Increase in plasma K+ levels can leadto acidemia.
Increase in plasma H+ levels can leadto hyperkalemia.
Plasma K+ levels can compromise theability of the kidney to regulate H+excretion.
A relationship exists between the K andthe H ion levels of the blood
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[ K+]o(hyperkalemia) [ K+] into cellsH+ leaves cells toblood for countering K+ into the cell [plasma H+]acidemia.
In an opposite manner, [ K+]o(hypokalemia) alkalemia.
[plasma H+](acidemia)K+ leave cells into blood[ plasma K+](hyperkalemia).
In an opposite manner, [plasma H+](alkalemia) hypokalemia.
Plasma K+ levels at the time of onset of either acidemia oralkalemia affect the ability of the kidney to compensate forthe acid-base disturbance.
Renal handling of calcium andphosphate
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Renal handing of calcium
All segments of the nephron reabsorb calcium except thedescending limb of the loop of Henle.
Calcium moves from the tubular fluid into the epithelialcells by passive diffusion down a concentration gradient.
On the basal lateral side of the cells, it leaves either inexchange for Na ions or by means of an ATP-requiringcalcium efflux pump.
Reabsorption is influenced by parathyroid hormone (PTH)
and calcium levels. An increase in plasma calcium levels reduces Ca++
reabsorption , while an increase in PTH results in anincrease in Ca++ reabsorption.
Renal handling of calcium andphosphate
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Renal Handling of Phosphate
Phosphate is reabsobed in the proximal tubule coupledwith sodium reabsorption.
Phosphate reabsorption exhibits saturation. The maximum capacity of this reabsorptive system is close
to the amount of phosphate normally filtered.
Parathyroid hormone (PTH) inhibits renal phosphate
reabsorption. PTH lowers the transport maximum of theNa-phosphate co-transporter, reducing phosphatereabsorption and increasing phosphate excretion.
IX. MicturitionUrinary excretion
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Urinary excretion is the renal important
function for maintaining normal metabolismand homeostasis of internal environment inthe human body.
Urinary excretion
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Volume and Pressure Relationship Curve in the Bladder
Volume (mL)
Pressureinthe
Bladder(cmH2O
)
Bladder
Contractive Wave
Urinary excretion
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PressureintheB
ladder(cmH2O
)
Volume (mL)
Volume and Pressure Relationship Curve in the Bladder
Reflex of urinary excretion
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Reflex of urinary excretion
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Clinic Problem is related to Reflex of Urinary excretion
Summarization
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Summarization
PLEASE TAKE DOWN
Summary on renal physiology
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Consideration after class
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1. Please describe the uropoietic elementary process .2. What are the influential factors of glomerular filtration
3. Please describe main position , patterns and mechanism of
Na+ reabsorption.
4. Please describe physiological function and secretion
regulation of ADH.
5. Please describe physiological function and secretion
regulation of aldosterone.
6. What is the mechanism of water diuresis
Guide of Reference
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1. . . . : , 2000.
2. , , . . : , 2000.
3. , , . . : , 2001.
4. , . . , 1991.
5. . . , 2002.
6. . . , : , 2005.
7. Berne RM, Levy MN, Koeppen BM, Stanton BA. Physiology, 5th ed, St Louis:
Mosby, 2004.
8. Guyton AC, Hall JE. TEXTBOOK OF MEDICAL PHYSIOLOGY, 10th ed,
Philadelphia: W.B. Saunders Co, 2000.
9. Charles Seidel. BASIC CONCEPTS IN PHYSIOLOGY: a students survival guide
(Great for Course Prep and USMLE), Houston: McGraw-Hill Co Inc, 2002.
10. Koeppen BM, Stanton BA. Renal physiology, 3rd ed, Health Scicece Asia: Elsevier
Science, 2002.
Navigation for Web Address
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1.http://clem.mscd.edu/~raoa/bio2320/uriphys/
2.http://www.bmb.psu.edu/courses/bisci004a/urin/urinary.htm
3.http://www.cat.cc.md.us/~dhargrov/ppp/urinary/
4.http://www.cat.cc.md.us/~dhargrov/ppp/urinary/sld005.htm
5.http://sciences.aum.edu/bi/B12100/cadams/urinary.htm
6.http://www.yiyee.com/mdinter/zhyfenke-mnk.htm
7.http://www.zgxl.net/sljk/imgbody/mnxt.htm
http://clem.mscd.edu/~raoa/bio2320/uriphys/http://www.bmb.psu.edu/courses/bisci004a/urin/urinary.htmhttp://www.bmb.psu.edu/courses/bisci004a/urin/urinary.htmhttp://www.cat.cc.md.us/~dhargrov/ppp/urinary/http://www.cat.cc.md.us/~dhargrov/ppp/urinary/http://www.cat.cc.md.us/~dhargrov/ppp/urinary/sld005.htmhttp://www.cat.cc.md.us/~dhargrov/ppp/urinary/sld005.htmhttp://sciences.aum.edu/bi/B12100/cadams/urinary.htmhttp://sciences.aum.edu/bi/B12100/cadams/urinary.htmhttp://www.yiyee.com/mdinter/zhyfenke-mnk.htmhttp://www.yiyee.com/mdinter/zhyfenke-mnk.htmhttp://www.zgxl.net/sljk/imgbody/mnxt.htmhttp://www.zgxl.net/sljk/imgbody/mnxt.htmhttp://www.zgxl.net/sljk/imgbody/mnxt.htmhttp://www.zgxl.net/sljk/imgbody/mnxt.htmhttp://www.yiyee.com/mdinter/zhyfenke-mnk.htmhttp://www.yiyee.com/mdinter/zhyfenke-mnk.htmhttp://www.yiyee.com/mdinter/zhyfenke-mnk.htmhttp://www.yiyee.com/mdinter/zhyfenke-mnk.htmhttp://sciences.aum.edu/bi/B12100/cadams/urinary.htmhttp://sciences.aum.edu/bi/B12100/cadams/urinary.htmhttp://www.cat.cc.md.us/~dhargrov/ppp/urinary/sld005.htmhttp://www.cat.cc.md.us/~dhargrov/ppp/urinary/sld005.htmhttp://www.cat.cc.md.us/~dhargrov/ppp/urinary/http://www.cat.cc.md.us/~dhargrov/ppp/urinary/http://www.bmb.psu.edu/courses/bisci004a/urin/urinary.htmhttp://www.bmb.psu.edu/courses/bisci004a/urin/urinary.htmhttp://clem.mscd.edu/~raoa/bio2320/uriphys/ -
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Formation and excretion ofUrine
Question
Answer
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