Formation and Excretion of Urine

Wang Guoqing
Department of Physiology, Medical School, Soochow University, Suzhou 215123, China

Chapter 8

E-mail:wangguoqing@suda.edu.cn Tel:0512-62096158; 13506212030

Chapter outline
I. II. IV. V. VI. Functional renal anatomy Renal blood flow Transport in the renal tubule and collecting duct Urinary concentration and dilution Regulation of urine formation

III. Glomerular filtration

VII. Clearance

VIII.Renal regulation of acid-base balance

IX. Micturition

Excretion pathway
Respiratory system ()
Large intestine ()

Skin ()
Kidney ()**

Excretory Approach

Urinary System

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, 25dihydroxyvitamin D3, aldosterone and erythropoietin(EPO).

Body water homeostasis (balance)

I. Functional renal anatomy

The nephron is the basic subunit of the kidney. It is composed of two components: the glomerulus and the renal 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 collecting duct, each with unique characteristics. Capillaries surround kidney tubules enabling exchange between blood and tubular fluid.

1.Basic kidney structure

2. Nephron structure

Renal Tubules

Nephron is composed of two components: the glomerulus and the renal tubule.

Nephron structure

Nephron is composed of two components: the glomerulus and the renal tubule.

Nephrons can reach to renal medulla

 Cortical nephron The nephrons have their glomeruli located in the outer and middle portion of the renal cortex are called cortical nephrons.
Juxtamedullary nephron The nephrons have glomeruli that lie deep in the renal cortex near the medulla and have long loops of Henle that are deep into the medulla are called juxtamedullary nephron.


Cortical Nephron

Juxtamedullary Nephron

85% A A

15%

3. Glomerulus
Called Capillary Tufts

Under the Electronic Microscope

Glomerulus
Blood Out

Blood In

Relationship visualized as a fist (Glomerulus, in) and a balloon (Bowman`s capsule, out)

juxtaglomerular apparatus The juxtaglomerular apparatus consists of the juxtaglomerular cells, the macula densa and the extraglomerular mesangial. juxtaglomerular cell The juxtaglomerular cells are specialized myoepithelial cells in the media of afferent arteriole close to the glomerulus.

Juxtaglomerular apparatus

JG cells can secrete Renin. JG cells serve as baroreceptor in afferent arteriole.

4. Glomerular filtration membrane

Space
porous

The epithelial cells of Bowman`s capsule called

 Glomerular filtration membrane The barrier between the capillary blood and the fluid inside the Bowmen's capsule is called glomerular filtration membrane.

Glomerular filtration membrane

Glomerular filtration membrane is impermeable to blood cell and plasma protein.

Pores

5. Renal tubule

The renal tubule is divided into four sections: proximal tubule, loop of Henle, distal tubule and collecting duct.

Glomerulus

renal corpuscle

(Bowman capsule)

proximal tubule

Nephron

proximal convoluted tubule

renal tubule

henle loop

distal convoluted tubule

Collecting duct

distal tubule

II. Renal blood flow (RBF) Renal blood flow distribution

95%

Renal blood flow (RBF)

Renal blood flow distribution

1. A second capillary networks called the peritubular capillaries

a first capillary network

a second capillary network

These capillaries surround specific segments of the tubule, and they return water and substances reabsorbed by the tubule to the general circulation, as well as deliver needed nutrients to the tubule.

Peritubular capillaries
Under the electronic microscope

Higher plasma colloid osmotic pressure in the peritubular capillaries is in favor of tubular reabsorption.

2. vasa recta

3. Characteristics of renal blood flow **

Large blood flow400 ml/min100g Renal blood volume 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

4. Determinants and regulation of RBF

RBF is determined by systemic arterial blood pressure and renal vascular resistance (renal sympathetic vasoconstrictor nerve control). RBF demonstrates autoregulation. Autoregulation involves afferent not efferent arterioles. Autoregulation is explained either by the myogenic hypothesis or tubuloglomerular feedback.

Autoregulation of RBF and GFR

Autoregulation means simply regulation of blood flow by the tissue itself. Whenever on excessive amount of blood flows through a tissue., the local vasculture constricts and decreases the blood flow forward to normal.
Glomerular Filtration Rate Renal Blood Flow or Glomerular Filtration Rate

Renal Blood Flow (RBF)

80 150 Systemic Arterial Pressure (mm Hg) The kidney maintains a constant blood flow (autoregulation) and glomerular filtration rate over the physiological range of systemic arterial pressure.

Autoregulation of RBF and GFR

Mechanism of autoregulation Two hypotheses describe autoregulation:

myogenic and tubuloglomerular feedback. 1.The myogenic hypothesis: When systemic arterial pressure increases RBF, the afferent arterioles are stretched. This stretch stimulates them to contract increasing their resistance and maintaining a constant RBF. If RBF decreased, then the opposite would occur. 2. Tubuloglomerular feedback involves an interaction between the distal tubules and the afferent arterioles. The beginning portion of the distal tubule passes close to the afferent arteriole, and together they form a specialized structure called the juxtaglomerular apparatus. Specialized epithelial cells in this portion of the distal tubule, called macula densa cells, sense the amount of NaCl (sodium chloride) in the tubular 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 passing by the macula densa cells. In response to this increased NaCl, a yet unidentified substance is released that causes afferent arteriolar constriction. This constriction reduces RBF, GFR, and the amount of NaCl delivered to the macula densa cells. If RBF were to decrease, then the opposite would occur.

Tubuloglomerular feedback
NaCl

NaCl

5. Nerve innervation of kidney

Renal sympathetic vasoconstrictor nerve control the smooth muscle of afferent glomerular arteriole and efferent glomerular arteriole, renal tubule and juxtaglomerular 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 and chemical stimulation toward central nervous system.

 ,,.

Process of urine formation

Three steps:
Glomerular filtration Renal tubule/collecting duct reabsorption Renal tubule/collecting duct secretion and excretion Material transport of renal tubule/collecting duct

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

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 move from inside to outside the tubule. Secretion is the process by which substances move from outside to inside the tubule. Excretion refers to substances that pass from the kidney into the bladder. it is the ability of the kidney to selectively move specific substances into and out of the tubule in a very controlled and coordinated manner that makes normal kidney function so critical to life.

Explanation for some terms

1. Glomerular filtration rate (GFR)

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 as percentage of the total renal plasma flow that passes through both kidneys.

2. Factors affecting glomerular filtration rate

Effective filtration pressure Filtration coefficientKf

(1) Glomerular effective filtration pressure

The effective filtration pressure of glomerulus represents the sum of the hydrostatic and colloid osmotic forces that either favor or oppose filtration across the glomerular capillaries.

Formula*:
Glomerular Effective Plasma colloid filtration pressure capillary pressure osmotic pressure

intracapsular pressure

(2) Filtration coefficientKf

Under the effective filtration pressure (EFP) driving force, liquid volume passing through filtration membranes per unit time. Two determinants of Kf filtration membranes area (s) permeability coefficient of filtration membranes (K) Kf = k s

 Structure of filtration membrane

3. Factors affecting glomerular filtration**

Change of effective filtration pressure Change of filtration coefficient

GFR Kf S PGCGCPBC
EFP
GFR: glomerular filtration rate
Kf : permeability coefficient

S:

glomerular filtration membrane area

PGC: glomerular capillary pressure

GC: plasma colloid osmotic pressure PBC: hydrostatic pressure in bowman

Changes in renal blood flow

Determinants and regulation of GFR and RBF

GFR is determined by the balance of forces acting across the filtration membrane. The forces that drive fluid out of the glomerulus are the capillary blood pressure (PGC) and the osmotic 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 the osmotic pressure (GC) of the blood within the glomerulus. The difference between these four forces determines the net filtration pressure, which is approximately 15 mm Hg. Net filtration pressure* = (PGC +BC) (PBC +GC) = (55+0)(15+25) = 15 mm Hg BC is zero. Explanation Filtration coefficient (Kf), a factor reflects permeability of filtration membrane.

Net filtration pressure

4. Regulation of GFR
Changes in systemic arterial pressure, the radius of the renal arterioles, and the filtration coefficient normally regulate GFR. 1. If systemic arterial pressure increases, then the pressure in the glomerular capillaries will increase and GFR will increase. The opposite will happen if systemic arterial pressure decreases. 2. Renal arteriolar resistance. (see next illustration) 3. Filtration coefficientThe filtration coefficient can be altered by the contractile activity of an additional set of cells located among the podocytes. These cells are called mesangial cells. These cells can be stimulated to contract, and when this occurs they decrease the area available for filtration and thus decrease the filtration coefficient and GFR. 4. Clinic diseases: Starvation / Burn GFR,Renal Stones GFR

5. Interaction between RBF and GFR

As discussed above, an increase in efferent arteriolar resistance produces opposite effects on RBF and GFR. RBF decreases and GFR increases. Under normal situations, blood leaving the glomerular capillary bed is at a higher osmotic pressure (GC) than the blood entering because of the fluid lost as ultrafiltrate. This rise in GC is not sufficient to significantly limit GFR. However, with a large increase in efferent resistance, RBF is reduced enabling GC to increase to such an extent that GFR is reduced. Therefore, GFR does not increase as much as expected with an increase in efferent arteriolar resistance because of the relationship between GFR, RBF, and GC.

Regulation of GFR with different arteriolar diameters

PGC
Decreased Afferent Arteriolar Diameter

GFR

Glomerular Capillary

PGC Decreased Efferent Arteriolar Diameter GFR Changes in arteriolar resistance before (afferent) and after (efferent) the glomerular capillary bed have different effects on capillary hydrostatic pressure (PGC) and therefore on glomerular filtration rate (GFR).

Effects of different arteriolar resistance on GFR

Effects of different arteriolar resistance on GFR

Effects of different arteriolar resistance on GFR

Effects of different arteriolar resistance on GFR

Nervous and humoral regulation of RBF and GFR

Nervous regulation
Renal sympathetic nerve:
Hypovolemia, noxious stimulation or agitation, etc.sympathetic nervous activity afferent glomerular arteriole contraction RBF and GFR; Hypervolaemiasympathetic 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.

Summarization
PLEASE TAKE DOWN

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 glomerular barrier, but all low-molecular-weight substances are freely filtered. Key terms: GFR, EFP, FF, Autoregulation

IV. Transport in the renal tubule and collecting duct

1. Overview of tubule properties Permeability properties of the luminal and basolateral membranes of the epithelial cells lining renal tubules are different, 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]

Reabsorption and secretion in the renal tubule and collecting duct

Definition
Transport Renal tubular reabsorption* () Tubular reabsorption denotes the transport of substances from 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.

 Transport patterns
Passive transport
diffusion, permeation, facilitate diffusion, solvent daggling

Active transport
sodium pump, hydrogen pump, calcium pump (symport or antiport)

Transport pathway:
Paracellular pathway transcellular pathway

2. Reabsorption of the renal tubule and collecting duct

General situation
Proximal tubule reabsorbs 67%of the filtered Na+, Cland 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 the filtered Na+ and Cl-

Renal tubule reabsorption of salt and water

3. Proximal tubule reabsorption of salt 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 and water

Proximal Tubular Cell Na+ Na+ ATP K+ Glucose & amino acids

Basal lateral membrane

The major mechanisms by which molecules move across the epithelium of the proximal tubule are diagramed in this figure.

BLOOD

Cell 1
H+

Na+

TUBULAR FLUID

Water

Cell 2
Luminal membrane

Proximal tubule reabsorption of Na+

Proximal tubule reabsorption of salt and water

4. Proximal tubule reabsorption of glucose and amino acids

Reabsorption of glucose and amino acids is coupled to the reabsorption of Na ions. Glucose reabsorption is overwhelmed when blood glucose is very high (diabetes). [daiebi:ti:z, -ti:s]

Proximal tubule reabsorption of glucose

Proximal tubule reabsorption of glucose

Relationship between plasma glucose and filtration rate of glucose

Relationship between plasma glucose and reabsorption rate of glucose

Relationship between Plasma Glucose and Excretion Rate of Glucose

renal glucose threshold* When the plasma glucose concentration increases up to a value about 180 to 200 mg per deciliter, glucose can first be detected in the urine, this value is called the renal glucose threshold.

Summary about Glucose

Graph Questions

5. Proximal tubule reabsorption of bicarbonate ions

Bicarbonate reabsorption requires Nadependent H ion secretion. Bicarbonate reabsorption occurs indirectly through the formation of CO2 and H2O.

Proximal tubule reabsorption of bicarbonate ions

TUBULAR FLUID Na+ + HCO3BLOOD HCO3- + H+ H2CO3 Na+ H+ + HCO3H2CO3 CA

CA H2O + CO2

CO2 + H2O

Reabsorption of bicarbonate ions in proximal tubule requires the formation and breakdown of carbonic acid (H2CO3) within the tubular fluid and epithelial cells. The enzyme carbonic anhydrase (CA) is essential for this process to occur. Some diuretics work by inhibiting the carbonic anhydrase enzyme.

Proximal tubule reabsorption of bicarbonate ions

6. Loop of Henle reabsorption of salt 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 the tritransporter in the ascending limb.

Loop of Henle reabsorption of salt and water

Ascending limb of the loop of Henle: a Na-K-Cl ion tritransporter for reabsorption of salt
Tubular Lumen Fluid Blood

Na+-2Cl--K+ tritransporter

Tubule epithelial Cell CELL

Place is the ascending limb of the loop of Henle

Counter-current multiplication
An osmotic gradient is established in the interstitial space 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 countercurrent multiplication.

Counter-current dissipation

Counter-current exchange

Counter-current multiplication
Assuming that initially all fluid within the loop has the same osmolarity (panel A) the tritransporter will reabsorb Na, K, and Cl from the tubular fluid creating an osmotic gradient of 200 mOsm between the interstitial space and the tubular fluid. The ascending limb is not permeable to water so water cannot follow. The descending limb is not permeable to salt so it cannot enter from the interstitial space. However, the descending limb is permeable to water so water is reabsorbed into the interstitial space. A new steady state is established (panel B). At this point new fluid enters from the proximal tubule displacing the fluid within the loop. This disrupts the steady state (panel C).Through the reabsorption of salt by the ascending limb and water by the descending limb, a new steady state is established (panel D). Notice that an osmotic gradient is being established in the interstitial space from the top to the bottom of the loop. It is the result of the loop structure and the different permeabilities of the two limbs of the loop. Fluid leaving the ascending limb is hypotonic compared to the fluid entering because more salt than water is reabsorbed. We will see in a later section that the interstitial osmotic gradient is critical for water reabsorption.

A
300 300 300 300 300

B
Equilibrium State
400 400 400 400 400 400 200 200 200

Water 300 Reabsorption

300
300

300 300
300 300

400 400

200
200

Na-K-Cl 400 400 Reabsorption

C
300 400 300 400 400 400 400 200 200 400 400 400

D
Equilibrium State
350 350 150

350 350
350 350 500 500 500 500

150
150 300 300

400

400

Increasing Osmotic Gradient

The 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.

Counter-current exchange of vasa recta

7. Distal tubule reabsorption of salt and water

More salt than water is reabsorbed. Na and Cl ions reabsorbed together. The distal tubule retains some of the properties of the ascending limb of the loop of Henle in that it is not very permeable to water and reabsorbs Na and Cl ions. The reabsorption of Na and Cl ions occurs through a co-transport carrier protein on the luminal side of the epithelial cell that combines the movement of one Na and Cl ion into the cell. This reabsorption is driven by the Na ion concentration gradient established by the Na-K-ATPase on the basal lateral side of the epithelial cell.

Distal tubule reabsorption of salt and water

Tubular Fluid Tubule epithelial Cell Blood

Lumen Tubule epithelial Cell

Symporter

Tubule epithelial Cell

8. Collecting duct reabsorption of salt and water

The permeability of the collecting duct to Na ions and water is variable. Antidiuretic hormone (ADH or Vasopressin, VP) increases the permeability of the collecting duct to water. Aldosterone increases the reabsorption of Na ions by the collecting duct.

Collecting duct reabsorption of Na+

Tubular Lumen Fluid
Epithelial Cell of the Collecting Duct

Blood

Epithelial Cell of the Collecting Duct

Effect of antidiuretic hormone (ADH) on the permeability of the collecting duct to water
ADH release

Epithelial Cell of the Collecting Duct Concentrated Urine

Effect of antidiuretic hormone (ADH) on the permeability of the collecting duct to water
ADH not release

Epithelial Cell of the Collecting Duct Dilute Urine

Antidiuretic Hormone (ADH or vasopressin, VP)

Mechanism of ADH or VP in the collecting duct for water reabsorption

Antidiuretic hormone, also known as vasopressin, a posterior pituitary hormone, increases the number of aquaporin channels in the membrane of the epithelial cells increasing water reabsorption. In the presence of ADH, water can leave the collecting duct in response to the osmotic gradient.

Relationship between plasma osmolarity and plasma vasopressin

Mechanism of aldosterone in the collecting duct for Na+ reabsorption

Epithelial Cell of the Collecting Duct

Epithelial Cell of the Collecting Duct

Aldosterone,a hormone secreted by the adrenal cortex, acts on collecting duct in several ways to increase Na reabsorption.

9. Collecting duct secretion of K 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 the luminal membrane of specialized epithelial cells of the collecting duct called principle cells. This secretion is down a concentration gradient established by the Na-KATPase located on the basolateral membrane. In the presence of aldosterone, more channels are opened and secretion is increased. Specialized cells of the collecting duct, called intercalated cells, are responsible for H ion secretion. This secretion is due to an active transport process that moves H ions from the inside of epithelial cell to the tubular fluid. The activity of this transporter is increased by aldosterone.

Collecting duct secretion of K and H ions

Tubular Lumen Fluid
Epithelium of the Collecting Duct

Blood

principle cell

Channels
+ aldosterone
Cl-

intercalated cell + aldosterone

Epithelium of the Collecting Duct

10. NH3 secretion is related to H+and HCO3transport

60% of NH3 secretion from glutaminate ( ), 40%from glycine () NH3 secretion promotes H+ secretion and HCO3reabsorption, in favor of renal acids excretion and alkaline reabsorption.

NH3

NH3

NH4

V. Urinary concentration and dilution

Urinary dilution Urinary concentration The loops of Henle are countercurrent multipliers The vasa recta are countercurrent exchangers Urea plays a special role in the concentrating mechanism

1. Overview
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 dilution 2. Definition

Plasma osmotic pressure (POP)300 mmol/L 300mOsm/kg H2O Urine osmotic pressurePOP, 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 kidney is damaged.

3. Mechanism of urinary concentration and dilution

Uinary dilution

Na+Cl- ADH Na+

 Urinary concentration

Forming mechanisms of hypertonicity in the medulla

Countercurrent multiplication of Henle's loop

Countercurrent exchange of vasa recta Counter-current theory

U
vasa recta

 Countercurrent multiplication Countercurrent multiplication is the process where by a small gradient established at any level of the loop of Henle is increased (multiplied) into a much larger gradient along the axis of the loop.

Countercurrent multiplication of Henle's loop

: NaCl NaCl NaCl urea recycling NaCl

NaClurea

Countercurrent exchange of vasa recta

NaCl

Process of urinary concentration and dilution

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

Regulatory patterns: Autoregulation () Nervous regulation () Humoral regulation ()
Significance

Maintenance of internal environment homeostasis.

2. Autoregulation in kidney
osmotic diuresis Solute concentration of renal tubular fluid Mannitol () clinic use

Different from water diuresis *

The volume of urine increases when water intake exceeds body needs, it is resulted from suppression of ADH secretion.

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 to increased tubular inflow. This phenomenon is referred to as glomerular-tubular balance.

3. Nervous regulation
Renal sympathetic nerve receptor activation contracts afferent and efferent glomerular arteriole inducing decreased RBF and GFR . receptor activation increases proximal convoluted tubule reabsorbing Na+ and other solutes; receptor activation promotes juxtaglomerular cell releasing renin; Homeostasis of Na+and water maintained. Renal sympathetic nerve involved in reflex: cardiopulmonary receptor reflex; Kidney Kidney reflex.

4. Humoral regulation
Renin-angiotensin-aldosterone systemRAAS -- Renal kallikrein-kinin system (-) Atrial natriuretic peptideANP EndothelinET

Nitric oxideNO
VasopressinVP Antidiuretic hormoneADH

Catecholamine, CA
Prostaglandin, PG ()

Renal regulation of salt and water balance

Sensing alterations in salt balance Salt balance, principally NaCl concentration, is assessed by monitoring osmolarity. Salt levels are changed by adjusting water reabsorption through the action of antidiuretic hormone (ADH). ADH* increases the number of open aquaporin channels in the collecting duct thereby increasing water reabsorption.

Renal regulation of salt and water balance

[NaCl]o Cells shrink

Signal to

Sensing alterations in water balance

Water balance is assessed by monitoring blood volume through changes in blood pressure. Water levels are changed by adjusting salt reabsorption through the renin-angiotensin-aldosterone system. Increased sympathetic nerve stimulation directly increases renal secretion of renin. Decreased distal tubule Na-load directly stimulates renal renin secretion. Increased volume stimulates the secretion of atrial natriuretic peptide form the atria.

Sensing alterations in water balance

Sensing alterations in water balance

Renin-Angiotensin--Aldosterone system (R-A-A-S).

+
Increased sympathetic nerve stimulation directly increases renal secretion of renin.

Angiotensin-also directly stimulates Na+ reabsorption by cells of the proximal tubule.

Effects of ANP on kidney

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 water reabsorption 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

Renal regulation of salt and water balance Relationship of osmolarity and volume

5. Reflex response to dehydration*

Dehydration results from an imbalance between water intake and water loss

Dehydration initiates reflexes to conserve both salt and water . Dehydration reduces blood pressure , which reduces GFR and RBF independent of other factors. 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.

Reflex response to dehydration *

With sweating (running) induced dehydrationwater volumeand osmolarityblood pressureGFR,RBFwater and salt excretion Blood pressurebaroreceptor mediated reflex response sympathetic nerve activityR-A-A-Swater and salt reabsorptiondiminish dehydration

Sympathetic nerve activityafferent arteriolar constriction GFR,RBF diminish dehydration

Blood pressureGFR and the distal tubule NaloadThe distal tubular epithelial cells stimulatereninR-A-A-S Extracellular osmolarityADH releasewater reabsorption Water volumeand osmolaritythirst occursdrink water

Na+

RSSA

RSSA

Na+

VII. Renal clearance Research method of kidney function

Renal clearance ** The volume of plasma per unit time needed to supply its quantity of substance excreted in the urine per unit time.

Clearance*
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 time that had all of a particular substance removed by the 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

1 g/mL Glomerular Capillary Efferent Arteriole

Afferent Arteriole Bowman`s Capsule

125 mL/min 125 g/min

Proximal Tubule

1 mL/min
125 g/mL 125 g/min Urine

Peritubular Capillary

This figure illustrates the principle of clearance and how it can be used to determine glomerular filtration rate.

Clearance = GFR
Creatinine, that is normally present in the blood and is not reabsorbed and minimally secreted by the kidney. By measuring urine flow rate and the concentration of creatinine in the blood and urine, 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

Glucose clearance

Penicillin clearance

Clearance for use

The clearance equation can also be used to calculate renal plasma flow (RPF) if a substance with an additional property is used. This additional property is that all of it needs to be removed from the blood by the kidney through a combination of filtration and secretion. Para-aminohippuric acid (PAH) clearance equals the RPF. RBF = RPF / (1 - Hct). (hematocrit, Hct)

Significance of renal clearance

Estimate renal function; Determine glomerular filtration rate (GFR ) Determine renal blood flow (RBF) Presume renal tubular transport effect Free-water clearance

Afferent arteriole

Distal convoluted tubule

Efferent arteriole

Bowman capsule

Glomerulus

micropuncture

VIII. Renal regulation of acid-base 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 the blood.

Renal regulation of acid-base balance

Normal Blood pH Value 7.357.45 CO2 + H2O H2CO3 H+ + HCO3-, H+ is volatile acid Increasing ventilation will blow off more CO2 driving the reaction to the left and lowering the H+ concentration. Decreasing ventilation will allow CO2 to accumulate driving the reaction to the right and increasing the H+ concentration. Other acids named fixed acids. (such as sulfuric and phosphoric acids ). Kidneys role (keeps appropriate level of bicarbonate ions / excretes the fixed acids produced by the body / secretes hydrogen 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 condition is called alkalemia (alkalosis). Vomiting

Renal regulation of acid-base balance

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

(Disodium salts) Na2HPO4

TUBULAR FLUID

Renal Tubular Epithelial Cell Glutamine NH3

Na++NaHPO4NH3+H+ Na+

Formation of titratable acid in the proximal tubule is one way by which the kidney generates new bicarbonate ions in response to acidemia. The H+ ion secreted by the epithelium is excreted as NaH2PO4 (titratable acid) leaving a bicarbonate ion behind.

BLOOD

HCO3- + HCarbonic acid (H2CO3)

H+

H+

H++ NaHPO4-

(Monosodium salts) NaH2PO4 Urine

Renal production of bicarbonate ions

Renal production of bicarbonate ions

Tubular Lumen Fluid
Epithelium of the Collecting Duct

Blood

(New HCO3- )

Epithelium of the Collecting Duct

Renal production of bicarbonate ions

Renal secretion of H ions

Tubular Lumen Fluid
Epithelium of the Collecting Duct

Blood

principle cell Channels

[H+]=410-8 M pH=7.4

+ aldosterone
Cl-

Pump
[H+]=310-5 M

intercalated cell

+ aldosterone

pH=4.5

Epithelium of the Collecting Duct

H ion secretion in the collecting duct leads to acidification of the urine. Collecting duct H ion secretion is stimulated by aldosterone.

Renal compensation for alkalemia

When the blood contains excess base, the kidney excretes bicarbonate and does not generate additional bicarbonate. Increase bicarbonate excretion occurs because there are insufficient H ions to be secreted by the proximal tubules to reabsorb all the filtered bicarbonate. The excess bicarbonate is excreted. Also, the low level of H ions means that filtered sulfuric and phosphoric acids will not be titrated and so no additional bicarbonate will be generated. In these ways, the kidney attempts to lower the blood bicarbonate concentration compensating for the alkalemia.

Renal compensation for alkalemia

Renal compensation for acidemia

When the blood contains excess H ions, the kidney excretes H ions and generates additional bicarbonate. In the presence of excess H ions, there are plenty of H ions to reabsorb all the filtered bicarbonate. In addition, the filtered fixed acid will be titrated generating additional bicarbonate ions. Also, the excess H ions stimulate the metabolism of glutamine by the kidney and the production of even more bicarbonate. Finally, the collecting duct increases its secretion of H ions. The combined effects of complete bicarbonate reabsorption , new bicarbonate generation, and the secretion of H ions helps the body compensate for the acidosis.

Renal compensation for acidemia

concentration

Relationship Between plasma K Ion Concentration and Acid-base Status Increase in plasma K+ levels can lead to acidemia. Increase in plasma H+ levels can lead to hyperkalemia. Plasma K+ levels can compromise the ability of the kidney to regulate H+ excretion.

A relationship exists between the K and the H ion levels of the blood
[ K+]o(hyperkalemia) [ K+] into cellsH+ leaves cells to blood 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 or alkalemia affect the ability of the kidney to compensate for the acid-base disturbance.

Renal handling of calcium and phosphate

Renal handing of calcium
All segments of the nephron reabsorb calcium except the descending limb of the loop of Henle. Calcium moves from the tubular fluid into the epithelial cells by passive diffusion down a concentration gradient. On the basal lateral side of the cells, it leaves either in exchange for Na ions or by means of an ATP-requiring calcium 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 an increase in Ca++ reabsorption.

Renal handling of calcium and phosphate

Renal Handling of Phosphate
Phosphate is reabsobed in the proximal tubule coupled with 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 the Na-phosphate co-transporter, reducing phosphate reabsorption and increasing phosphate excretion.

IX.

Micturition
Urinary excretion

Urinary excretion is the renal important function for maintaining normal metabolism and homeostasis of internal environment in the human body.

Urinary excretion
Pressure in the Bladder( cm H2O )

Bladder Contractive Wave

Volume (mL)

Volume and Pressure Relationship Curve in the Bladder

Urinary excretion
Pressure in the Bladder( cm H2O ) Volume (mL)

Volume and Pressure Relationship Curve in the Bladder

Reflex of urinary excretion

Reflex of urinary excretion

Clinic Problem is related to Reflex of Urinary excretion

Summarization
PLEASE TAKE DOWN

Summary on renal physiology

Consideration after class

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
. . . : , 2000. , , . . : , 2000. , , . . : , 2001. , . . , 1991. . . , 2002. . . , : , 2005. 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. 1. 2. 3. 4. 5. 6. 7.

Navigation for Web Address

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

Formation and excretion of Urine

Question

Answer

THANKS FOR YOUR ATTENTION