You are on page 1of 128

Renal

Physiology
 Fluid intake and output are balanced during Steady State
Conditions
 Body fluid – total body water is approximately 60% -
74% of body weight
Distribution of Water
 Intracellular fluid
 Fluid inside the cell
 2/3 of total body weight
(about 40% of total body
weight)
 Major cations: K and Mg
 Major anions: proteins and
organic phosphate (ATP,
ADP, AMP)
Distribution of Water
 Extracellular fluid
 Fluid outside the cell
 1/3 of total body weight (about 20% of total body weight)
 Composed of:
 Interstitial fluid (3/4 of ECF)
- Composition is the same as that of plasma except that
it has little protein; Has ultrafiltrate of plasma
- Major cation: Na
- Major anion: Cl
 Plasma (1/4 of ECF)
- Major plasma: albumin and globulin
- Major cations: Na ions
- Major anions: Cl and HCO3
Distribution of Water
 Transcellular fluid
 Considered as specialized ECF
 Small compartments include:
 Synovial
 Peritoneal
 Pericardial
 Interlobular
 CSF
Water Content Regulation
 Water content is regulated so that the total volume of
water in the body remains constant
 Kidneys – primary regulators of water excretion
 Regulation process:
 Osmosis
 Osmolality
 Baroreceptors
Major sources of Water
a) Ingested in the form of liquid or water in the foods
b) Synthesized in the body as a result of oxidizing
carbohydrates (Cellular metabolism)
Daily Loss of Water
 Insensible water loss
 Fluid loss in sweat
 Water loss in feces
 Water loss to the kidney
Constituents of ECF and ICF
 Concentration of positively charged ions is highly greater
(about 2%) in the plasma than in the interstitial fluid
(Donnan Effect)
 Ionic composition of plasma and interstitial fluid are similar
Shifts of Water between
Compartments
 Water shifts between ECF and ICF so that the
osmolarities of the two compartments become equal
 Osmolarity of ICF and ECF are assumed to be equal
after a brief period of equilibration
 Osmosis  net diffusion of water across a selectively
permeable membrane from a region of high water
concentration to one that has lower water concentration
 Osmoles  total concentration of solute particles
regardless of their exact composition
Types of Solution
a) Solution that will cause a change in cell volume
(impermeant solutes)
 Isotonic solution – solution that will not cause a
cell to shrink or swell; water concentration in the ICF
and ECF are equal and solutes cannot enter or leave
the cell
 Hypotonic solution – lower concentration of
impermeant solutes; cause swelling of cell
 Hypertonic solution – higher concentration of
impermeant solutes; cause shrinking of cell
Types of Solution
b) Concentration of solution based on osmolarity
 Isosmotic solution – osmolarity the same as the cell
 Hyperosmotic solution – osmolarity is higher
compared to the normal ECF
 Hypo-osmotic solution – osmolarity is lower
compared to the normal ECF
Examples of Shift of Water
between Compartment
 Infusion of isotonic NaCl
 Diarrhea
 Excessive NaCl intake
 Sweating
 Adrenocortical insufficiency
Infusion of Isotonic NaCl
 Also called isosmotic volume expansion
 Addition of isotonic fluid
1. ECF volume increases, but there will be no change in osmolarity
of ECF or ICF
 Reason: osmolarity is unchanged, there will be no shift of water
between ECF and ICF
2. Plasma protein concentration and hematocrit decreases
 Reason: loss of ECF concentrates the protein and RBC
 Because ECF osmolarity is unchanged, the RBC will not shrink
or swell
 Arterial blood pressure increases because ECF volume increases
Diarrhea
 Also called isosmotic volume contraction
 Loss of isotonic fluid
1. ECF volume decreases, but there will be no change in
osmolarity of ECF and ICF
 Because osmolarity is unchanged, there will be no shift
of water between ECF and ICF
2. Plasma concentration and hematocrit increases because the
loss of ECF concentrates the protein and RBC (ECF
osmolarity is unchanged: RBC will not shrink or swell)
3. Arterial blood pressure decrease because ECF volume
decreases
Excessive NaCl Intake
 Hyperosmotic volume expansion
 Addition of NaCl
1. Osmolarity of ECF increases – addition of osmoles
to ECF
2. Water shift from ICF to ECF – ICF osmolarity
increases until it is equal to ECF osmolarity
3. Volume of the ECF increases and the volume of the
ICF decreases
Sweating
 Hyperosmotic volume contraction
 Loss of water
1. Osmolarity of ECF – increases because sweat is
hypo-osmotic
2. ECF volume decreases – loss of volume in the sweat
3. ICF osmolarity increases until it is equal to ECF
osmolarity – water shifts out of ICF
4. ICF volume decreases due to shifting of water out of
the ICF
Adrenocortical Insufficiency
 Hypo-osmotic contraction
 Loss of NaCl
1. Osmolarity of ECF – decreases because the kidney loss
more NaCl than water as a result of the lack of aldosterone
in adrenocortical insufficiency
2. ECF volume decreases because water shifts into cells
3. ICF osmolarity decreases until it equals ECF osmolarity,
and ICF volume increases – water shift into the cells
4. Protein concentration decreases – increase in ECF volume
5. Hematocrit is unchanged – water shifts into the RBC,
increasing their volume and offsetting the diluting effect of
the ICF volume expansion
Clinical Abnormalities of
Fluid Volume
HYPONATREMIA
- Plasma Na concentration is reduced below normal
- Causes:
a) Loss of Na
 Hypo-osmotic dehydration
 e.g. Diarrhea, Vomiting
b) Excess water
 Hypo-osmotic overhydration
 e.g. excessive secretion of ADH
Clinical Abnormalities of
Fluid Volume
HYPERNATREMIA
- Plasma Na concentration is elevated above normal
- Causes:
a) Water loss
 Hyperosmotic dehydration
 e.g. Lack of ADH, diabetes insipidus
b) Excess Na
 Hyperosmotic overhydration
 e.g. excessive secretion of aldosterone
Edema
 Presence of excess fluid in the body tissue
 Occurs mainly in the ECF (can also involve the ICF)
 Conditions that cause intracellular swelling:
1. Depression of the metabolic system of the tissue
2. Lack of adequate nutrition to the cell (e.g. deterioration of Na-K
pump  Na enter the cell)
 Causes of ECF edema:
1. Abnormal leakage of fluid from the plasma to the interstitial
spaces across the capillaries
2. Failure of the lymphatic to return fluid from the interstitium
back into the blood
3. Lack of protein
Edema
Walrus Puppy/ Anasarca
Conditions that Cause
Extracellular Edema
1. Increased capillary pressure
2. Decreased plasma protein
3. Increased capillary permeability
4. Blockage of lymph
Increased Capillary Pressure
a) Excessive kidney retention of salt and water
1. Acute or chronic kidney failure
2. Mineralocorticoid excess
b) High venous pressure
1. Heart failure
2. Venous obstruction
3. Failure of venous pump
c) Decreased arteriolar resistance
1. Excessive body heat
2. Insufficiency of sympathetic nervous system
3. Vasodilator drugs
Decreased Plasma Protein
 Reduction of plasma protein concentration
- Plasma colloid osmotic pressure falls
- Increase capillary filtration throughout the body as
well as ECF edema
a) Loss of protein in urine
b) Loss of protein from denuded skin areas (burns and
wounds)
c) Failure to produce proteins
 Liver disease
 Serious protein or caloric malnutrition
Increased Capillary
Permeability
1. Immune reactions that cause release of histamine and
other immune products
2. Toxins
3. Bacterial infections
4. Vitamin deficiency, esp. vitamin C
5. Prolonged ischemia
6. Burns
Blockage of Lymph
 Plasma proteins that leak into the interstitium have no
other way to be removed
 Increased protein concentration raises the colloid
osmotic pressure of the interstitial fluid
 Draws more fluid out of the capillaries
1. Cancer
2. Infections
3. Surgery
Three major factors that cause
increased capillary filtration of fluid
and protein into the interstitium
1. Increased capillary hydrostatic pressure
2. Decreased plasma colloid osmotic pressure
3. Increased capillary permeability, which causes leakage
of proteins and fluid through the pores of the
capillaries
Functions of Kidney in Homeostasis
1. Excretion of metabolic waste products and foreign
chemicals, drugs and hormone metabolites
2. Regulation of water and electrolyte balance
3. Regulation of body fluid osmolality and electrolyte
concentration
4. Regulation of acid-base balance
5. Regulation of arterial blood pressure
6. Secretion, metabolism, and secretion of hormones
7. Gluconeogenesis
8. Regulation of erythrocyte production (erythropoeitin)
9. Regulation of 1,25 dihydroxy Vit. D3 production
(calciferol)
Anatomy of Mammalian Kidney

 Cortex: outer area


 Renal Columns
 Medulla: inner area
 Renal pyramids
 Renal papilla
 Calyces
 Pelvis
 Ureter
Nephron (Urineferous tubules)
 Basic functional unit of the kidney
1. Renal corpuscles (Malphigian Body)
a) Glomerulus
b) Bowman’s capsule
 Parietal layer
 Visceral layer
2. Renal tubules
a) Proximal tubule
b) Loop of Henle
c) Distal nephron
Types of Nephron
1. Cortical nephron
- Comprises 85% in humans and most other animals
2. Juxtamedullary nephron
- Vasa recta is essential in the formation of concentrated
urine
- Pig (3%), Human (14%), Cat (100%)

* Both types of nephron empty its contents into the collecting


tubule and ducts that proceeded from the medulla to the renal
pelvis
Distribution of Blood at
the Glomerulus
 Renal Blood Flow (RBF)
- Rate at which the blood flows to the kidney
 Renal Plasma Flow (RPF)
- 25% of the cardiac output
- Directly proportional to the pressure difference
between the renal artery and the renal vein and
inversely proportional to resistance of renal
vasculature
Autoregulation of RBF
 Accomplished by changing renal vasculature resistance as
arterial pressure changes, thus maintaining a constant
flow
 RBF remains constant over the range of arterial pressure
from 100 – 200 mmHg
Distribution of Blood at
the Glomerulus
 Glomerular Filtration Rate (GFR)
- Rate at which glomerular filtrate is formed
- Measured in ml per minute
 Filtration Fraction
- Ratio of GFR/RPF
Kidney Solute Load
 Plasma load for the substance
- Amount of any substance contained in plasma that is
presented to the kidney each minute

 Tubular load of plasma membrane


- Part of the plasma load that filters into the Bowman’s
capsule
- Amount that will be presented to the tubule ,
regardless of whether or not it is re-absorbed
Nerve Supply
 Provided by fiber from the sympathetic nervous system
 Activity: regulation of RBF, GFR and salt and water re-
absorption by the nephron accompanied by
vasoconstriction initiated by reflexes through the
vasomotor center in the medulla and pons
 Increase sympathetic tone elicits renin secretion from the
granular cells and enhances Na reabsorption (and water)
from the nephron segment
Overview of Renal Tubular
Function
 The constancy of the body’s internal environment is maintained
by the continuous functioning of the nephrons. As blood passes
through the kidneys, the nephrons clear the plasma of some
substances (e.g. urea) while simultaneously retaining other
essential substances (e.g. water, glucose)
 Substances are removed by:
 Glomerular filtration
 Renal tubular secretion
 Substances needed are retained by:
 Renal tubular absorption  returned to the blood by
reabsorption process
Renal Processes in Urine Formation
1. Glomerular filtration
2. Tubular re-absorption – quantitatively more
important than tubular secretion in the formation of
urine
3. Tubular secretion – determines the amount of K and
H ions and a few substances that are excreted in the urine
a) Change the composition of GF which began
immediately on entering the proximal tubule
b) Continuous throughout the length of the nephron so
that tubular fluid does not become urine until it enters
the renal pelvis
 No compositional changes in urine beyond the collecting
duct except in horse  addition of mucus
 Glomerular filtration, tubular re-absorption and tubular
secretion are regulated according to the needs of the
body
 e.g. Increase in Na in body = increase filtration
 e.g. Decrease re-absorption = increase excretion of Na

Urinary excretion = Filtration Rate – Re-absorption


+ Secretion
Glomerular Filtration
 First step in urine formation
 Kidney has functional counterpart of two capillary beds
a) Glomerulus
- High pressure system (high hydrostatic pressure favoring
filtration)
- Similar to the arterial end of a typical muscle capillary
- Impermeable to protein
b) Peritubular capillaries
- Perfused with blood coming from the glomerular capillary bed
- Low pressure system (low hydrostatic pressure favoring re-
absortion)
- Similar to the venous end
Glomerular Filtration
 End products of metabolism that must be cleared from the
blood: (poorly absorbed ; excreted in large amount in urine)
1. Urea
2. Creatinine
3. Uric acid
4. Urate
 Electrolytes are highly re-absorbed (only small amount
appears in urine): Na, Cl, and HCO3
 Substances completely re-absorbed from the tubules (do not
appear in urine): amino acid and glucose
Glomerular Filtration
 Glomerular filtrate is:
- Essentially protein free and devoid of cellular elements
including RBC
- Concentration is similar to the concentration of
plasma
 Plasma has low molecular weight substances such as
calcium and FA that are not freely filtered because they
are partially bound to the plasma
Glomerular Filtration Rate (GFR)
 Volume of glomerular filtrate formed each minute by all the
nephrons in both kidneys
 Measurement of GFR
- Inulin is filtered but not re-absorbed or secreted by the renal
tubules
- Clearance of inulin is used to measure GFR
 Estimate of GFR with BUN and plasma creatinine
- Both BUN and plasma creatinine increases when GFR decreases
- GFR decreases with age
- Plasma creatinine remains constant because of decreased muscle
mass
Advantages of High GFR
1. Allows the kidney to rapidly remove waste products
from the body that depends primarily on GFR for their
excretion (most waste products are poorly re-absorbed
by the tubules and depend on high GFR for effective
removal from the body)
2. Allows all the body fluids to be filtered and processed
by the kidney many times each day
3. Allows the kidneys to precisely and rapidly control the
volume and composition of the body fluids
Filtration Fraction
 Function of the RBF that is filtered across the glomerular
capillaries
 Equals to GFR/RPF
 Normally about 20% of the RBF is filtered
 80% leaves the glomerular capillaries by efferent
arterioles and enters peritubular capillary circulation
Filtration Membrane
Glomerular Capillary Membrane
a) Endothelium – perforated with fenestra (large hole) which have
negative charges that hinder the passage of plasma protein
b) Basement membrane – surrounds the endothelium
– consists of a meshwork of collagen and proteoglycans fibrillae that
have large spaces through which can filter large amount of water and
small solutes; prevent filtration of plasma
c) Layer of epithelial cells (Podocytes) – surrounds the outer
surface of the capillary basement
– have podocytes that are separated by gap called slit pore
* Filterability of solutes is inversely related to their size
* Negatively charged large molecules are filtered less as compared with
positively charged molecules of equal molecular size
Starling Forces
 Determinant of GFR
 Driving forces for GF in the net ultrafiltrate pressure
across the glomerular capillaries
 Filtrate always move forward
 GFR can be expressed by the Starling equation

GFR = Kf (PGC – PBS) – (ПGC – ПBS)


Filtrate coefficient of GF
 Glomerular barrier
 Anionic glycoprotein lines the filtrate barrier and
restricts the filtration of negatively charged plasma
protein
 Anionic charge on the barrier may be removed in
glomerular disease resulting to proteinuria
Glomerular Capillary
Hydrostatic Pressure (PGC)
 Promote filtration
 Increased by dilation of the afferent arteriole or
constriction of the efferent arterioles
 Increase causes increase in net ultrafiltration pressure
and increase GFR
Bowman’s Space
Hydrostatic Pressure (PBS)
 Outside the capillaries which opposes filtration
 Increased by constriction or blockage of the ureters
 Increase causes decrease in net ultrafiltration pressure
and decrease in GFR
Glomerular Capillary
Oncotic Pressure (ПGC)
 Colloid osmotic pressure of the glomerular capillary
plasma in GFR
 Normally, it increases along the length of the glomerular
capillary because filtration of water increase the protein
concentration of glomerular capillary blood
 Increases by increase in protein concentration
 Increase causes a decrease in net ultrafiltration pressure
and a decrease in GFR
 Opposes filtration
Bowman’s Space
Oncotic Pressure (ПBS)
 Usually zero because the small amount of filtered
albumin are subsequently re-absorbed
 Colloid osmotic pressure of the protein in Bowman’s
capsule
 Promotes filtration
Physiologic Control of GF
and RBF
1. Sympathetic Nervous System
- Decreases GFR
- Constrict the renal arteriole
- Most important in reducing GFR during severe, acute
disturbances lasting for a few minutes
2. Hormonal and Autacoid Control of Renal Circulation
 NE and Epinephrine
 Endothelin
 Angiotensin II
 Endothelin derived Nitric Acid
 Prostaglandin and Bradykinin
Autoregulation of GFR
and RBF
- Feedback mechanism intrinsic to the kidneys
- Keep the RBF and GFR relatively constant despite
marked changes in arterial pressure
- Major functions:
 Maintain a relatively constant GFR
 To allow precise control of renal excretion of water
and solutes
 Prevent extreme changes in renal excretion
Renal Tubuloglomerular Feedback
Mechanism in Autoregulation of GFR
- Has to components that act together to control GFR
1. Afferent arteriolar feedback mechanism
2. Efferent arteriolar feedback mechanism
- Feedback mechanism that:
 Link change in NaCl concentration at the macula densa with the
control of renal arteriolar resistance
 Ensure a relatively constant delivery of NaCl to the distal tubule
 Help to prevent spurious fluctuation in renal excretion
 Provide signals to both afferent and efferent arterioles for efficient
autoregulation during changes in arteriolar pressure via the
juxtaglomerular apparatus
Juxtaglomerular Apparatus
 Consists of:
1. Macula densa cells
- Specialized group of epithelial cells at the initial portion of distal
tubule that comes in close contact with afferent and efferent
arteriole
- Contains Golgi apparatus directed toward the arteriole
- Side of the tubule that faces the glomerulus
2. Juxtaglomerular cells
- Specialized smooth muscle cell located in the walls of afferent
and efferent arterioles that make contact with the macula densa
- Have secretory granules that contain renin
Macula Densa Feedback
Mechanism for Autoregulation
Arterial pressure

Glomerular hydrostatic pressure

Proximal NaCl GFR


reabsorption
Macula densa NaCl

Renin

Angiotensin II

Efferent arteriolar resistance Afferent arteriolar resistance


Factors Affecting
Glomerular Filtration
 Hydrostatic filtration and oncotic pressure
 Capillaries
 Mesangial cells
 Renal blood flow
Role of Hydrostatic Filtration
and Oncotic Pressure
 Fluid movement is proportional to:
a) Permeability
b) Balance between hydrostatic and oncotic
 When hydrostatic pressure exceeds oncotic pressure,
reabsorption occurs
Role of Capillaries
 Main mechanism that alters intercapillary pressure is the
contractile state of the pre-capillary sphincters
Role of Mesangial Cells
 Intercapillary mononucleated, stellate cells embedded in
an extracellular matrix surrounded by glomerular
capillaries
 Certain mesangial cells exhibit contractile response to
angiotensin II, ADH and norepinephrine
 This type of mesangial cell possesses angiotensin II
receptors and microfilaments similar to those smooth
muscle cells
 Vasoactive substances modulate the filtration coefficient
by stimulating intrarenal angiotensin II production via
generation of cyclic adenosine 3,5 monophosphate
Role of Mesangial Cells
 Locally the glomerular angiotensin II caused mesangial
contraction, reducing the GF surface area and the
filtration coefficient
 The effect of angiotensin II on mesangial cells is a decline
in glomerular flow
Renal Blood Flow
 Although the major determinant of the GFR is the
hydrostatic pressure with the glomerular capillaries, the
RBF through the glomeruli has an effect on the GFR
 When the rate of RBF increases so does the GFR
Autoregulation of
Arterial Pressure
 Intrinsic phenomena in which the range of arterial
pressure, GFR and RBF remain quite constant (e.g. 90 –
190 mmHg)
 Observed in renal capillaries (also occurs in capillaries of
muscles)
 Virtually absent at mean arterial pressure below 70
mmHg
 Necessary for autoregulation of GFR
Myogenic Autoregulation
of RBF
 Second mechanism that contributes to the maintenance
of a relatively constant RBF and GFR
 A phenomenon or the ability of individual blood vessels
to resist stretching during increase arterial pressure
 Contraction of the vascular smooth muscle prevent
distension and at the same time, by raising vascular
resistance, help to prevent excessive increase in RBF and
GFR when arterial pressure increases
Explanations for Renal
Autoregulation
1. According to Myogenic Hypothesis
- An increase on pressure stretches the blood vessel walls
- Cause the smooth muscle in the vessel wall to contract
- Decrease the diameter of the vessels
- Decrease blood pressure causes the opposite changes
2. According to Tubuloglomerular Feedback Hypothesis
- Transient increase in GFR resulting from an increase in blood pressure
- Increase solute delivery to macula densa
- Increase in tubular fluid NaCl concentration
- Increase Na re-absorption by macula densa
- Constriction of the nearby afferent arteriole
- Blood flow and filtration are lowered to a more normal value
Factors that Determine RBF
a) The afferent arteriole
- Has larger diameter than efferent arteriole
- Major site of autoregulatory resistance to blood flow
- The GFR and RBF changes in the same direction
1) Constriction of afferent arteriole
- Decrease both the renal plasma flow and GFR
- Increase in vascular resistance proximal to the
glomeruli leads to a decrease in renal plasma flow
- Decrease in hydrostatic pressure within the glomerular
capillaries lead to a decrease in GFR
2) Dilation of afferent arteriole
- Increases both the renal plasma and GFR
- Decrease in vascular resistance proximal to the
glomeruli leads to an increase in renal plasma flow
- Increase in glomerular capillary perfusion leads to an
increase in GFR
Factors that Determine RBF
b) When resistance to flow is altered in the
efferent arterioles, GFR and renal plasma flow
and the renal plasma change in opposite
directions
- Change in efferent arteriolar resistance do affect the
filtration fraction
1) Constriction of efferent arteriole
- Decrease the renal plasma flow and increases the GFR
- Increase in vascular resistance distal to the glomeruli
- Leads to a decrease in renal plasma flow
- Increase in the hydrostatic pressure within the
glomerular capillaries
- Leads to increased GFR
- Following an increase in efferent arteriolar resistance;
filtration fraction increases
2) Dilation of efferent arteriole
- Increases renal plasma flow and decrease the GFR
- Decrease in vascular resistance distal to the glomeruli
- Leads to an increase in renal plasma flow
- Decrease in hydrostatic pressure within the
glomerular capillaries
- Leads to decreased GFR
- Following a decrease in efferent arteriolar resistance;
filtration fraction decreases
Factors that Determine RBF
c) The juxtaglomerular apparatus
- Region in cross section often appearing as a roughly
triangular region bounded by the macula densa and
the afferent and efferent arterioles as they enter and
leave the glomerulus
- Contains three major cell types:
1. Macula densa
2. Extraglomerular mesangial cells
3. Granular cells (Juxtaglomerular cells)
Routes/Passageway of
Substances
1. Transcellular route – through the cell membrane
2. Paracellular route – intercellular spaces (e.g. pores,
water channels/aquaporins)

 Na ions move through both routes (most are transported via


the transcellular ways)
 Water is re-absorbed via paracelllular way (including the
substances dissolved in it)
Transcellular Pathway
 Used for transepithelial transport
 Approximately 2/3 of the Na transport in the PT is
active and transcellular
 Three principal mechanisms of Na transport in PT
a) Electrogenic Na-cotransport with sugars and AA
b) Electroneutral Na-cotransport with phosphate
and inorganic ions (acetate, citrate and lactate)
c) Electroneutral counter transport with H
Paracellular Pathway
 Follows the lateral intercellular spaces
 Used for passive transepithelial transport
 Approximately 1/3 of NaCl transport is passive and paracellular
a) Paracellular pathway for Cl reabsorption in PT
1. Water moves out of the tubule secondary to Na
reabsorption
2. Active transport of Na leaves the luminal membrane
negatively charged with respect to the interstitial fluid
b) Paracellular pathway for K – exists in the interspaces of
the PT and thick segments of the ascending limb of loop of
Henle
Renal Capillary Membrane
Transport
1. Filtration – bulk transport of fluid with its dissolved small solutes
across a membrane
a) Hydrostatic pressure difference between the glomerular capillaries
and Bowman’s capsule promotes filtration
b) Concentration in the plasma and the ultrafiltrate in Bowman’s
capsule are the same
c) Filtered load – amount of solute transported across the glomerular
membrane per unit time
- Proportional only to GFR and the force that affect filtration
namely:
 Hydrostatic pressure
 Oncotic pressure
Renal Capillary Membrane
Transport
2. Simple Diffusion
- Principal mode of transport in interstitial space and
within cells
- driving force for diffusion of ions is consist of two
gradients:
a) Concentration gradients
b) Electric (voltage) gradients
Renal Epithelial Transport
 Basolateral membrane transport system
 Apical membrane transport system
Basolateral Membrane
Transport System
 Primary Active Transport
- Transport that is coupled actively to an energy source such
as the hydrolysis of ATP
- e.g. Na-K pump, H pump, H-K pump
 Facilitated Diffusion
- Involves a passive transport of a substance by a protein
carrier from a region of higher concentration to a region of
lower concentration
- Translocate glucose from the intracellular fluid across the
membrane to the interstitial fluid
 Osmosis
Apical Membrane
Transport System
 The apical surface of the renal epithelium of the proximal
tubules differ from other cell membrane in that: simple
diffusion plays almost no role in the transport of Na, Cl, H,
glucose and AA
 The movement of Na across the luminal membrane is
favored by the electrochemical gradient, but the bulk of
Na transport is mediated by specific transport membrane
protein and not by simple diffusion
Two Transport Mechanism of AMTS
1. Diffusion mechanism
- Available for Na to pass through the tight junction in
association with Cl
- Most of the Cl that is reabsorbed never enters the cell
2. Carrier secondary active transport
- Transport of Na down its gradient provides energy for
active (uphill) transport of other solutes (e.g. glucose,
AA
a) Co – transport (symport) – Na - Glu; Na - AA
b) Counter transport (antiport) – Na - K
Transepithelial Transport
 The difference between apical and basolateral membrane
properties for the transepithelial transport of all solutes,
which can occur via the transcellular and paracellular
pathway
Other Mechanisms Involved
1. Passive transport
2. Osmosis
3. Ultrafiltration – mechanism in which capillary walls
behave like the venous end of most capillaries
- A passive process driven by hydrostatic and colloid
osmotic pressure gradients
4. Pinocytosis – active transport mechanism of reabsorption
of protein
Transport mechanism of Na
1. Na diffuses across the luminal membrane into the cell
2. Na is transported across the basolateral membrane to the interstitial
fluid by Na-K pump
3. Na, water, and other substances are reabsorbed from the interstitial
fluid into the peritubular capillaries by ultrafiltration
4. Secondary active transport of Na
 Two to more substances interact with a specific membrane protein
carrier and are transported together across the membrane
 Energy release from the substances (e.g. Na) is used to drive
another substance (e.g. Glucose) as in Na co-transport with
glucose
Transport Maximum
 Limit to the rate at which the solute can be transported for
most substances that are actively reabsorbed or secreted
 Limit is due to saturation of the specific transport system
involved when the amount of solute delivered to the tubule
(tubular load) exceeds the capacity of the carrier protein
and specific enzyme involved in the transport process
 Point at which carrier is saturated
 Substances that are primarily re-absorbed do not
demonstrate transport maximum
 Glucose and Para-aminohippuric acid (PAH)
Proximal Tubular Re-absorption
 High capacity of reabsorption
 Reabsorb about 65% Na, Cl, K and H2O
 Reabsorb about 90% bicarbonate
 100% glucose
 50% urea
 Special characteristics of PT
a) Epithelial cells are highly metabolic and have large number of
mitochondria to support active transport
b) Has extensive brush border on the luminal side of the
membrane
Proximal Tubular Re-absorption
 1st half
- Na is reabsorbed by co-transport along with glucose,
AA, bicarbonates, and organic ions – leaving behind a
solute that has a high concentration of Cl
 2nd half
- Little glucose and AA remain to be reabsorbed
- Na is reabsorbed mainly with Cl ions
- High Cl concentration (favors diffusion of Cl from the
tubular lumen through the intercellular junction into
the renal interstitial fluid)
Proximal Tubular Re-absorption
 Substances pass through cells of tubule wall and each cell
has:
1. Apical surface
2. Basal surface
3. Lateral surface
 Active transport of Na across the basal membrane from
cytoplasm to interstitial fluid linked to reabsorption of
most solutes
 Because of active transport, the concentration of Na is low
inside the cell and Na moves into nephron cell from
filtrate through the apical membrane.
Proximal Tubular Re-absorption
 Other substances moved by co-transport from the filtrate
into the nephron cell are substances which should be
retained by the body
 Substances transported:
 Through apical membrane: Na, Cl, glucose, amino acids
and water
 Through the basal membrane: Na, K, Cl, glucose, amino
acids and water
Proximal Tubular Secretion
 Bile salts, oxalate, urate catecholamine,
para-aminohippuric acid
 Drugs such as penicillin, salicylate, and toxins
Thin Descending Segment of LH
 Highly permeable to water
(20% reabsorbed)
 Water moves out of
nephron, solutes in.
volume of filtrate is
reduced by 15%
 Moderately permeable to
most solute including urea
and Na
 Does not absorb
significant amount of Na,
Cl, K
Thin Ascending Segment of LH
 Has lower re-absorptive
capacity
 Not permeable to water
but is permeable to solutes
 Solutes diffuse out of the
tubule and into the more
diluted interstitial fluid as
the ascending limb
projects toward the cortex
 Solutes diffuse into the
descending vasa recta
Thick Ascending Segment of LH
 Capable of active
reabsorption of Na, Cl,
and K (25%)
 Impermeable to water
 Fluid becomes diluted as
it flow toward the distal
tubule due to re-
absorption of large
amount of solute (impt
feature in allowing the
kidney to dilute or
concentrate urine)
Re-absorption in LH
Early Distal Tubule
 Have many of the same re-absorptive characteristics of
the thick ascending limb of LH
 Avidly reabsorb most of the ion including Na, K, Cl
 Virtually impermeable to urea and water
 Referred to as the diluting segment (dilute the tubular
fluid)
Late Distal Tubule and
Cortical Collecting Tubule
 Has similar functional characteristics
 Reabsorb Na and rate of absorption is controlled by
aldosterone
 Secretion of K ions from peritubular capillary blood into
tubular lumen is also controlled aldosterone
 Permeability to water is controlled by ADH
- With ADH  highly permeable to water
- Without ADH  not permeable to water
Late Distal Tubule and
Cortical Collecting Tubule
 Composed of two distinct types:
a) Principal cell
- Reabsorb Na and water from
the lumen
- Secretes K ions into the
lumen
b) Intercalated cells
- Reabsorb K ions
- Secretes H ions into the
tubular lumen
- Mediated by H ATPase
transport
- Play a key role in acid base
regulation of the body fluid
Two Steps in K Secretion
1. K enter the cell because of Na-K pump which maintain a high
intracellular K concentration
2. Once in the cell, K diffuses down its concentration gradient
across the luminal membrane into the tubular liquid
* Activity depends on ATP pump at the basolateral membrane
Mechanism of H Secretion
 Inside the cell, H is
generated by the action
of carbonic anhydrase
on CO2 to form
carbonic acid, which
dissociates into H and
bicarbonate
 H is secreted into the
tubular lumen
 Bicarbonate is
reabsorbed into the
basolateral membrane
Medullary Collecting Duct
 Reabsorb <10% of filtered water and Na
 Final site for processing urine
 Extremely important in determining the fluid output of water and
solution
 Epithelial cells are nearly cuboidal with smooth surfaces and
relatively few mitochondria
 Permeability of water is controlled by the level of ADH
 Permeability to urea, help raise the osmolarity in this region and
contribute to kidney’s overall ability to form a concentrated urine
 Capable of secreting H against a large concentration gradient
 Plays a key role in regulating acid base balance
Regulation of Tubular Re-absorption
1. Glomerotubular balance – ability of tubules to increase
re-absorption rate in response to increased tubular load
2. Hormonal control of tubular re-absorption
a) Aldosterone
b) Angiotensin II
c) ADH
d) Atrial Natriuretic Peptide
e) Parathyroid Hormone
3. Sympathetic Nervous System
Urine concentration Mechanism
1. Medullary Concentration Gradient
- In order to concentrate urine, the kidney must maintain a high
concentration of solutes in the medulla
2. Creating/Maintaining High Solute Concentration in Medulla
- Active transport of Na and co-transport of ions such as K and Cl and
other ions out of the thick portion of ascending limb into interstitial fluid
- Impermeability of ascending limbs of LH
- Vasa recta remove excess water and solutes that enter the medulla
without destroying the high concentration of solutes in interstitial fluid of
medulla
- Active transport of ions from collecting ducts into interstitial fluid of
medulla
- Passive diffusion of urea from CD, impermeability of ascending limb and
permeability of descending limb of LH to urea
Counter Current Multiplier
Counter Current Exchanger
Fig. 26.16
Diuretics
Potassium Secretion
Bicarbonate reabsorption and H secretion
Avian Kidney

You might also like