2. 2
Chief Functions of Renal System
1.Regulation of water & electrolyte balance
2.Regulation of acid & base balance
3.Excretion of waste products of protein metabolism, e.g.,
Urea from protein breakdown
Uric acid from nucleic acid breakdown
Creatinine from muscle creatine breakdown
End products of hemoglobin breakdown
4.Excretion of foreign chemicals, e.g., drugs, food additives,
pesticides, …etc.
5.Endocrine function: erythropoietin, renin, 1,25-dihydoxy-vitamin D.
6.Regulation of arterial pressure
7.Gluconeogenesis
3.
4. 4
FUNCTIONAL ANATOMY OF KIDNEYS &
URINARY TRACT
• The kidneys lie high on the posterior abdominal wall outside
peritoneum against the back, below the diaphragm & on either side
of the vertebral column.
• In adults each kidney is the size of a clenched fist & weighs ~150 g.
• Urine produced by the kidneys is delivered to the urinary bladder by
2 ureters.
• The bladder continuously
accumulates urine and periodically
empties its contents via urethra
under the control of an external
urethral sphincter – a process
known as micturition.
5. FUNCTIONAL ANATOMY: kidney
• Each kidney is formed of 2
distinct parts:
An outer cortex
An inner medulla.
medulla is divided into 8 to 10 cone-
shaped masses of tissue called renal
pyramids. The base of each pyramid
originates at the border between the
cortex and medulla and terminates in
the papilla, which projects into the
space of the renal pelvis, a funnel-
shaped continuation of the upper end
of the ureter. The outer border of the
pelvis is divided into open-ended
pouches called major calyces that
extend downward and divide into
minor calyces, which collect urine
from the tubules of each papilla.
6.
7. Nephron
the basic functional unit of kidney
1 million nephrons in each kidney
The kidney cannot regenerate new
nephrons.
The nephron is composed of 2 main
components:
A. The renal corpuscle
B. The renal tubule
11. 11
1. The Glomerulus:
- It is present in the cortex.
- Each glomerulus is formed of a tuft of capillaries that
are invaginated into the Bowman’s capsule.
- Blood enters the capillaries through the afferent
arteriole and leaves through the slightly narrower
efferent arteriole.
- Glomerular capillaries are unique in that they are
interposed between 2 arterioles. This arrangement
serves to maintain a high hydrostatic pressure (60
mmHg) in the capillaries, which is necessary for
filtration.
12. 12
2. The Bowman’s Capsule:
It is the proximal expanded portion of the renal tubule
forming a double-walled cup
outer parietal & inner visceral
13.
14.
15. Glomerular membrane
1.Capillary endothelium;
It has small holes fenestrated (70-90 nm).
It does not act as a barrier against plasma
protein filtration.
2.Basement membrane; (BM)
filamentous layer attached to glomerular
endothelium & podocytes, carry strong-ve
charges which prevent the filtration of
plasma proteins, but filters large amount
of H2O and solutes.
3.Podocytes;
Epithelial cells of visceral layer that line
the outer surface of the glomeruli.
They have numerous foot processes that
attach to the BM, forming filtration slits
(25 nm wide).
19. 19
THE NEPHRON
There are 2 types of nephrons in the kidney:
1. Cortical Nephrons: (80% of nephrons)
Their glomeruli lie in the outer layers of the cortex.
Their tubular system is relatively short.
Their loops of Henle penetrate only for a short distance into
the outer portion of renal medulla.
2. Juxtamedullary Nephrons: (20% of nephrons)
Their glomeruli lie at the boundary between cortex & medulla.
They have long loops of Henle, which dip deeply down into the
medulla toward the tips of the pyramids.
They play a major role in the process of urine concentration.
20. Types of nephrons
Items Cortical nephrons Juxtamedullary nephrons
% Of total 85 % 15%
Glomeruli Out part of cortex Inner part of cortex .
Loop of Henle Short i.e. dips to the
junction between
inner and outer
medulla.
Long i.e. dips deeply
into the medullary
pyramids to the
inner medulla
Blood supply Peritubular capillaries
No Vasa Recta
Vasa recta and
peritubular
capillaries
Special
function
Na reabsorption Urine concentration
JG apparatus Present Absent
Autoregulation Present Absent
21. Juxtamedullary Nephron Cortical Nephron
The efferent vessels of juxtamedullary glomeruli form long looped
vessels, called vasa recta which is important for urine
concentration.
22.
23.
24. So,why is the loop of Henle
useful?
• The longer the loop, the more
concentrated the filtrate.
• Importance: the collecting
tubule runs through the
hyperosmotic medulla more
ability to reabsorb H2O
Desert animals have long nephron
Loop More H2O is reabsorbed
26. 26
Juxtaglomerular Apparatus:
Each DCT passes between the afferent & efferent arterioles of its own
nephron. At this point there is a patch of cells with crowded nuclei in
the wall of the DCT called the macula densa. They sense the
concentration of NaCl in this portion of the tubule.
The wall of the afferent arteriole opposite the macula densa contains
specialized cells known as the juxtaglomerular cells (JG cells). They
secrete renin. They are volume & baroreceptor, stimutated by hypo
volemia or decreased renal perfusion pressure.
Mesangial or lacis cells –supporting cells
Together, the mesangial cell, macula densa & JG cells are called the
juxtaglomerular apparatus (JGA).
29. 1. Renin-Angiotensin System:
■ Most important mechanism for Na+ retention in
order to maintain the blood volume.
■ Any drop of renal blood flow &/or Na+, will
stimulate volume receptors found in juxtaglomerular
apparatus of the kidneys to secrete Renin which will
act on the Angiotensin System leading to
production of Angiotensin II.
30. Renin – Angiotensin
Vasoconstrictor Mechanism
• Main function –
(i) Control of BP
(ii)Regulation of ECF Volume
Renin – Secreted from – JG Cells
Stimulus – Low BP
Function – convert ATG to AT-I
ACE
AT-I → AT-II (in lungs endo cells)
31. Renin
Aldosterone
Adrenal
cortex
Corticosterone
Angiotensinogen
(globulin substrate )
(Lungs)
renal blood flow &/or Na+
++ Juxtaglomerular apparatus of kidneys
(considered volume receptors)
Angiotensin I (inactive decapeptide)
Converting
enzymes
Angiotensin II (octapeptide)
(powerful vasoconstrictor)
Angiotensin III(heptapeptide)
(powerful vasoconstrictor)
• Renin-Angiotensin System:
N.B. Aldosterone is the main regulator of Na+ retention.
angiotensinases
Angiotensin IV(hexapeptide)
38. 38
BLOOD VESSELS in the NEPHRONS
• Each kidney receives its blood supply from a renal artery,
which arises directly from the abdominal aorta.
• In the kidney, the renal artery progressively subdivides into
smaller branches until they form afferent arterioles, which
break up into a tuft of capillaries, the glomerulus. Then the
capillaries form the efferent arteriole.
• The efferent arteriole again subdivides to form peritubular
capillaries, which surround the various segments of the
renal tubules.
N.B. There are 2 sets of capillaries & 2 sets of arterioles!!
• The efferent arterioles of juxtamedullary nephrons form a
special type of peritubular capillaries called vasa recta.
They are straight & long capillaries that form hairpin
loops along side the loops of Henle.
They play an important role in the process of urine
concentration.
40. two capillaries beds
• glomerular capillaries:
Higher hydrostatic pressure( about 45 mmHg)
--- in favor of rapid fluid filtration ;
• peritubular capillaries:
Lower hydrostatic pressure ( about 10 mmHg)
---in favor of rapid fluid reabsorption;
41. Major Renal Capillaries
Glomerular capillary
bed
Peritubular capillary
bed
1. Receives bl from afferent
art.
Receives bl from efferent
art.
2. High presure bed 45- 55
mmHg
Low pressure bed 10- 13
mmHg
3.Represents arterial end of
cap.
Represents venous end of
cap.
4. allows fluid filtration. Allows fluid reabsorption.
42.
43. Characteristics of RBF:
1. High blood flow:
1200ml/min: 25% cardiac output
0.4 % of total body weight
300-400ml/100gm/min
A high blood flow is necessary for glomerular
filtration.
2.Distribution:
cortex 90%
outer medulla 9%
inner medulla 1% 10%
44.
45. The renal vascular resistance varies with the pressure so
that renal blood flow is relatively constant It is probably
produced in part by a direct contractile response to stretch
of the smooth muscle of the afferent arteriole. At low
perfusion pressures, angiotensin II also appears to play a
role by constricting the efferent arterioles, thus maintaining
the glomerular filtration rate.
46.
47. Inhibit ↑ afferent arterioler pressure
↓
↑ GFR
↓
↑ Solute absorption in PCT
↓
↑ Fluid delivered to DCT
↓
↑ NaCl entry in Macula densa cells
↓
↑ Na K ATPase activity
↓
↑ ATP hydrolysis
↓
↑ Adenosine formation
↓
↑ Via adenosine A1 receptors
↓
.↑ Calcium release
48. In every nephron, the macula densa senses changes in GFR by
measuring the tubular fluid flow rate.
If the tubular fluid flow rate increases, the macula densa signals to the
afferent arteriole to contract, thereby reducing GFR and normalizing
flow .
51. Impact of autoregulation
• Autoregulation:
– GFR=180L/day and tubular
reabsorption=178.5L/day
– Results in 1.5L/day in urine
• Without autoregulation:
– Small ↑ in BP 100 to 125mm Hg, ↑GFR by 25%
(180 to 225L/day)
– If tubular reabsorption constant, urine flow of
46.5 L/day
• What would happen to plasma volume?
52. Mechanism of urine formation
Kidney maintained homeostasis by removing unwanted
substances(urea, uric acid, creatinine) by glomerular
filtration & tubular secretion & retained useful
substances( water, Na, HCO3) by tubular reabsorption.
Most substances in the plasma are freely filtrated, so
that their concentrations in Bowman’s capsule are
almost the same as in the plasma.
Glomerular filtrate is called Ultrafiltrate of plasma because
it contains no protein and no cells.
53.
54.
55. • Glomerular filtration :- substances move from blood to
renal tubules.
Fluid and small solutes dissolved in the plasma such as
glucose, Na, K, Cl, HCO3- , other salts, and urea pass
through the membrane and become part of the filtrate.
• Reabsorption- denotes the active transport of solutes &
passive movement of water from tubular lumen in to the
peritubular capillaries i.e. the removal of a substance from
the filterate.
- glucose, water, proteins, phosphate, sulfate, calcium,
potassium, and sodium ions
• Secretion:- refers to the transport of solutes from pritubular
capillaries in to the tubular lumen, i.e. it is the addition of
substance to the filterate.
- drugs and ions
56. Urinary excretion =filtration -reabsorption + secretion
• Normal RBF -1.2 to 1.3L/min
• The glomerular filtrate is formed
at a rate of 125 ml/min. or 180
L/day. It passes to the renal
tubules.
• In the tubules, the tubular fluid is
subjected to the 2 main tubular
functions, reabsorption &
secretion.
• It is finally excreted as urine at a
rate of about 1-2 ml/min. or 1.5
L/day.
TUBULAR FUNCTION
57. Glomerular filtration
1)Glomerular membrane
Capillary endothelium;
It has small holes (70-90 nm). It does
not act as a barrier against plasma
protein filtration.
Basement membrane; (BM)
filamentous layer attached to
glomerular endothelium & podocytes,
carry strong-ve charges which
prevent the filtration of plasma
proteins, but filters large amount of
H2O and solutes.
Podocytes;
Epithelial cells that line the outer
surface of the glomeruli.
They have numerous foot processes
that attach to the BM, forming
filtration slits (25 nm wide).
58. Filterability of the Membrane
• Filterability is a term used to describe membrane selectivity
based on the molecular size and charge.
• Pore size would favor plasma protein (albumin) passage, but
negative charge on protein is repelled by the (-) charged
basement membrane (sialoproteins)
• Loss of this (-) charge causes proteinuria.
Changes in the permeability of glomerular membrane:
• GFR is directly proportional to the permeability of glomerular
membrane e.g. hypoxia, fevers, some renal diseases
increases this permeability.
59. 2)Composition of glomerular filtration
• a- Contents: - water
- ions: Na+, K+, Cl-
- freely filtered substances e.g. glucose, amino
acids.
- 0.03% albumin (molecular weight 6900).
• b- Osmolality: 300 mosmol/L, isotonic (same
osmolality as plasma).
• C- Specific gravity: 1010
• D- pH: drops to 6 in urine due to acidification by
the kidney.
60. GFR
3)GFR=volume of glomerular filterate formed each minute
by all the nephrons in both kidneys .
or
the amount of ultra filtrate formed by two kidneys per minute.
or
The volume of fluid filtered per unite time is called the glomerular
filtration rate .
Normal value:125ml/min,180L/day
The GFR is determined by
(1)Effective filtration pressure (EFP) and
(2) Glomerular capillary filtration coefficient (Kf)
GFR= Kf ☓ EFP
EFP= (PG − PB ) − (πG − πB )
EFP= (45-10)-(25-0)
EFP=10 mm of Hg
61. 4)Dynamics of glomerular filtration
• The rate of fluid exchange (i.e. filtration- absorption) at
any point along a capillary depends upon a balance of
forces called Starling forces.
• EFP represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration.
Forces favoring filtration:
Glomerular hydrostatic pressure(PG)
Bowman’s capsule colloid osmotic pressure (πB)=0
Forces opposing filtration：
Bowman’s capsule hydrostatic pressure (PB)
Glomerular capsule colloid osmotic pressure (πG)
EFP= (PG − PB ) − (πG − πB )
62. Glomerular filtration rate =Effective filtration pressure X
Filtration coefficient
GFR = EFP (l0) X Kf (12.5) = 125ml/min.
In both the kidneys GFR at 1 mm Hg EFP is called Kf
Kf = 12.5 ml/min/mmHg
- Kf is determined by 2 factors:
1- The permeability of the capillary bed.
2- The surface area of the capillary bed.
Kf is the product of the permeability and filtering surface area
of the capillaries .
Kf ↑ GFR ↑
Example:
diabetes mellitus thickness of glomerular membrane ↑ Kf
↓ GFR↓
63. Forces affecting filtration
Favoring Filtration Opposing Filtration
Glomerular hydrostatic
pressure
45 mm Hg
Bowman’s capsule hydrostatic
pressure
10 mm Hg
Bowman’s capsule colloid
osmotic pressure
0 mm Hg
Glomerular capillary colloid osmotic
pressure
25 mm Hg
Net = +10 mm Hg
65. Most waste products are poorly reabsorbed by the tubules and,
therefore, depend on a high GFR for effective removal from the
body.
A second advantage of a high GFR is that it allows all the body
fluids to be filtered and processed by the kidneys many times
each day. Because the entire plasma volume is only about 3
liters, whereas the GFR is about 180 L/day, the entire plasma
can be filtered and processed about 60 times each day. This
high GFR allows the kidneys to precisely and rapidly control the
volume and composition of the body fluids.
Importance of high GFR
66. It is the fraction of the renal plasma flow (RPF)
that becomes glomerular filtrate.
Filtration fraction = GFR / RPF
Normal value: about 16%-20% (125/660=19%)
(about 20% of the plasma flowing through the
kidney is filtered by the glomerular capillaries)
5)Filtration fraction
67.
68. 6)Factors Affecting the GFR.
Changes in renal blood flow
Changes in glomerular capillary hydrostatic pressure
Changes in systemic blood pressure
Afferent or efferent arteriolar constriction
Changes in hydrostatic pressure in Bowman's capsule
Ureteral obstruction
Edema of kidney inside tight renal capsule
Changes in concentration of plasma proteins: dehydration,
hypoproteinemia, etc (minor factors)
Changes in Kf
Changes in glomerular capillary permeability
Changes in effective filtration surface area
69. (1) Changes in glomerular hydrostatic pressure.
(1) Diameter of the afferent arterioles.
– VD of afferent arterioles ++ Hydrostatic pr. in
glomerular capillary ++ GFR.
– VC of afferent arterioles e.g ++ sympathetic activity -
- Hydrostatic pr. in glomerular capillary (HPGC) --
GFR.
(2) Diameter of the efferent arterioles.
– Moderate VC ++ Hydrostatic pr. in glomerular
capillary slight ++ of GFR.
(3) Arterial Blood Pressure:
Between 80 & 180 mmHg: GFR and RBF are kept
relatively
constant by autoregulatory mechanisms.
70.
71. 71
Changes in GFR by constriction or dilation of
afferent (AA) or efferent (EA) arterioles
72. Constriction of the afferent
arteriole reduces both the
RBF and theGFR, leaving
the filtration fraction
unchanged.
Efferent arteriole
constriction reduces RBF
but conserves GFR,
causing an increase
in the filtration fraction.
73. (2) Changes in Bowman’s Capsule hydrostatic
pressure
++ Hydrostatic pr in Bowman’s capsule e.g. stone in
ureter (ureteral obstruction) -- GFR .
(3) Change in glomerular colloidal osmotic pressure
Increased Colloidal osmotic pressure in glomerular
capillary
• e.g in dehydration decreased GFR.
Decreased Colloidal osmotic pressure in glomerular
capillary
• e.g in hypoproteinemia increased GFR.
(4) Functioning kidney mass
When the number of functioning nephrons decreases
e.g. in renal disease (failure), there is reduction of
filtration coefficient (kf) & decrease in GFR
(decreasing the filtering surface area).
74. 5) Changes in filtering surface area:
This is changed by contraction or relaxation of mesangial
cells.
They are contracted by vasopressin (ADH), adrenaline,
angiotensin II, prostaglandin F2 and sympathetic stimulation.
They are relaxed by prostaglandin E2, dopamine, cAMP and
ANP.
Contraction of mesangial cells → decrease surface area
available for filtration → decrease in Kf & decrease in GFR
and vice versa.
6) Regulation of GFR:
1.Autoregulation
2.Nervous regulation
3. Hormonal regulation
7) Measurement of GFR
75. Glomerular Versus Systamic filtaration
• 180 L/day
• Kf 100 times higher
• PG -45 mm of Hg
• Total capillary exchange
area-1.6m2 of which 2-3%
is available for filtaration.
Thus the glomerular
filtaration surface area
measures between 500-
810 cm2.
• 20 L/day
• Kf is less
• PG -25 mm of Hg
• Total capillary exchange
area-1000m2 of which
only 25% are open at
rest.
• Thus the systamic
filtaration surface area
measures about 250m2
76.
77. Or Is the amount of solute transported across the glomerular membrane per unit time.
78.
79. Tubular fluid concentration (TF )/ Plasma
concentration (PX) ratio
• The TF/PX ratio compares the concentration of a substance in
tubular fluid at any point along the nephron with its
concentration in plasma.
• The TF/PX ratio may be 1, <1, >1.
• TF/PX ratio of 1 signifies that either there has been no
reabsorption or reabsorption of the substance has been
exactly proportional to the reabsorption of water.
• TF/PX ratio of <1 signifies that reabsorption of a substance
has been greater than the reabsorption of water and its
concentration in tubuiar fluid is less than that of plasma.
• TF/PX ratio of >1 signifies that either the reabsorption of a
substance has been less than the reabsorption of water or
there has been secretion of the substance
80. Renal Tubular Transport Maximum (Tm)
• Tm= It refers to the maximum amount of
a given solute that can be transported
(reabsorbed or secreted) per minutes by
the renal tubules.
• Tm – pertains to solutes that are
actively transported.
• Tm=filtered load-excretion rate
• Substances that are passively
transported (urea) do not exhibit a
Transport Maximum(Tm)
81. Renal Transport
A) Active transport; against electrochemical gradient.
(1) Primary active transport
Requires energy directly from ATP.
Example; Na+ reabsorption in PCT
(2) Secondary active transport
-It does not require energy direct from ATP.
a) Co-transport
two substances bind to a specific carrier are cotransported in one direction.
b) Counter-transport
two substances bind to a specific carrier are
transported in two directions.
B) Passive reabsorption;
(1) Simple diffusion
Passive reabsorption of chloride & Osmosis of water
(2) Facilitated diffusion
Need carrier.
C) Pinocytosis
It is an active transport mechanism for reabsorption of proteins and
peptides in the proximal convoluted tubules.
82. d)Transepithelial transport
• Transcellular pathway:2/3rd
through the cell membranes
• Paracellular pathway:1/3rd
through the junctional spaces
• across the tubular epithelial
membranes into the renal
interstitial fluid
• through the peritubular
capillary membrane into the
blood.
84. Types of carrier proteins
– A uniport carrier: transport one substance.
– A symport carrier: transport two substances in the
same direction.
– An antiport carrier: transport two substances in the
opposite directions.
85. Mechanisms of Reabsorption
1. Passive transport
1). Down electrochemical gradient;
2). not require energy;
3). Mode : Diffusion,Osmosis,facilitated
diffusion
4). Example:H2O,glucose AA
86. 2. Active transport
1). Against an electrochemical gradient;
2). require energy;
3). Depend on carrier proteins that penetrate
through the membrane
4). divided into two types:
– Primary active transport: coupled directly to
an energy source(hydrolysis of ATP)
– Secondary active transport :coupled indirectly
to an energy source(an ion gradient)
87. Primary active transport is linked to
hydrolysis of ATP
• Importance: move solutes against an
electrochemical gradient
• energy source: hydrolysis of ATP
• Example: sodium-potassium ATPase
pump
89. Na+-K+ ATPase hydrolysis ATP release energy
Transport Na+ out of the cell into the interstitium
Transport K+ from the interstitium into the cell
The intracellular concentration of sodium is lower
(chemical difference)
The cell interior is electrically negative than the
outside (electrical difference)
Favor Na+ to diffuse from the tubular lumen
into the cell through the brush border
90.
91. Secondary active transport
• Co – transport:
glucose-sodium transport
amino acids -sodium transport
phosphate -sodium transport
Counter- transport:
H+-Na+ transport
92.
93. Co – transport of
Glucose (or amino
Acids) along with
Sodium ions through
The brush border of
The tubular epithelial
cells
94. - PCT is about 15 mm long and 55 μm in diameter.
- PCT wall is lined by single layer of epithelial cells
that are connected by tight junctions at their luminal
edges, but there is a space between the cells along
the rest of their lateral borders (lateral intercellular
spaces) which contains interstitial fluid.
- The luminal borders of cells have brush border due
to presence of large number of microvilli which
increase surface area for reabsorption. 65%-80% of
the reabsorbion function occurs in PCT.
- The PCT cells have large numbers of mitochondria
(energy supply).
SPECIFIC FUNCTIONS OF DIFFERENT TUBULAR
SEGMENTS
96. II. Loop of Henle:
• The loop of Henle with its 3 segments (that differ structurally &
functionally) contributes to creating a gradually increasing hyperosmolality
(300 1200 mosmol/L) in the renal medullary interstitium.
A. Thin descending limb:
- highly permeable to water. 20% of H2O is reabsorbed here.
- only moderately permeable to solutes.
Osmolality of tubular fluid gradually as loop dips deep into the medullary
pyramid (reaches 1200 mosmol).
B. Thin ascending limb:
- impermeable to water
- low absorptive power for solutes.
C. Thick ascending limb:
- impermeable to water
- high reabsorptive power for solutes: It actively reabsorbs 25% of filtered
Na+, K+, & Cl- (by 1 Na+, 2 Cl-, 1 K+ cotransport) to medullary
interstitium.
Osmolality of tubular fluid gradually as it reaches DCT (becomes
hypoosmotic). It is called the diluting segment.
98. 98
III. Distal Convoluted Tubule (DCT) & Collecting Duct (CD):
A. Late DCT & Cortical CD: 12%
(1) Principal Cells:
a. They actively reabsorb Na+ in exchange for K+ secretion. This
action is increased by aldosterone.
b. Antidiuretic hormone (ADH) causes reabsorption of H2O.
In the absence of ADH, the principal cells are impermeable to H2O.
(2) -Intercalated Cells:
- These cells secrete H+ .This action is increased by aldosterone.
C. Medullary CD:
• In this last portion of the nephron there is final adjustment of volume &
concentration of urine.
The permeability of this segment to water, same as that of the late
DCT & cortical CD, is variable & depends on the level of circulating
ADH (= facultative water reabsorption).
This part is also permeable to urea, that diffuses into the interstitium
when its concentration in tubular fluid due to H2O reabsorption.
Thus, urea contributes to the hyperosmolality of medullary
interstitium.
100. Summary of changes in osmolality of tubular fluid in
various parts of the nephron
101. Reabsorption and Secretion Along Different
Parts of the Nephron
Reabsorption in Proximal Tubule
• 100% Glucose, protein and Amino Acids
• 60% Sodium, Cl-, and H2O.
• 80%, HCO3-, K+.
• 60% Ca++.
• 50% of Filtered Urea.
• Secretion in Proximal Tubule
• Hydrogen secretion for acid/base regulation.
• Ammonia secretion for acid/base regulation.
• PAH.
• Creatinine.
• Uric acid.
• Penicillin.
102. Reabsorption of glucose:
• Position: proximal tubule.
• All the filtrated glucose is reabsorbed
under normal condition.
• Secondary active transport, accompanied
by the primary active transport of sodium .
103. 103
Trasport of individual substances -GLUCOSE
At normal blood glucose levels (~80 mg/dl), glucose is freely filtered at a
rate of 125 mg/min. (= plasma conc. X GFR = 80mg/dl x 125 ml/min.).
The amount filtered is completely reabsorbed from the upper half of PCT
by Na+-glucose cotransport
There is, however, a limited number of Na+-glucose carriers:
a- At a blood glucose level of less than 180 -200 mg/dl all the filtered
glucose can be reabsorbed because plenty of carriers are available.
b- At a blood glucose level of 180 -200 mg/dl glucose starts to appear in
urine.
This level of blood glucose is called the renal threshold for glucose. It
corresponds to a renal tubular load of 250 mg/min.
c- At a renal tubular load of glucose of 375mg/min, all the carriers are
saturated, i.e., the transport maximum for glucose, TmG, is reached.
Any further in filtered glucose is not reabsorbed & is excreted in urine.
104.
105.
106. Tubular maximum for glucose (TmG):
• The maximum amount of glucose (in mg ) that
can be reabsorbed per min.
• It equals the sum of TmG of all nephrons.
• Value; 300 mg/min in ♀ , 375 mg/ min in ♂.
Renal Threshold for Glucose
• Is approximately 180 mg/dl
• If plasma glucose is greater than 180 mg/dl:
– Tm of tubular cells is exceeded
– glucose appears in urine
109. Appearance of glucose in the urine (at the
threshold) occurs before the transport maximum
is reached. One reason for the difference
between threshold and transport maximum is
that not all nephrons have the same transport
maximum for glucose, and some of the
nephrons therefore begin to excrete glucose
before others have reached their transport
maximum. The overall transport maximum for
the kidneys, which is normally about 375
mg/min, is reached when all nephrons have
reached their maximal capacity to reabsorb
glucose.
111. Glucosuria
presence of glucose in urine
1. Diabetes mellitus
–blood glucose level > renal threshold.
2. Renal glucosuria
–It is caused by the defect in the glucose
transport mechanism.
3. Phlorhizin
–A plant glucoside which competes with
glucose for the carrier and results in
glucosuria.
112. Glucose
• filtration rate = (Pc x GFR)
• =80×125= = 100 mg/min
• reabsorption rate = 100 mg/min
– site = early portion of the proximal tubule
• secretion rate = 0 mg/min
• excretion rate = 0 mg / min
• Tm = 375 mg/min
• Ideal (predicted) renal threshold =80×375/100= 300
mg/dL
• actual renal threshold = 200 mg /dL (arterial)
180 mg/dL (venous) because 20mg/dl gets utilized
while passing through tissues.
– “splay”
120. At basolateral side of the tubular epithelial cell there is an
extensive Na+-K+ ATPase system (= Na+-K+ pump).
It pumps 3 Na+ actively out of the cell into the interstitium,
and at the same time carries 2 K+ into the cell.
But K+ will diffuse immediately back into the interstitium
due to:
(1) high concentration gradient &
(2) high permeability of epithelial cells to K+.
As a result of this there is:
- intracellular Na+ concentration
At luminal membrane there will therefore be passive
diffusion of Na+ into the cell along concentration gradient
created by the Na+-K+ pump. This diffusion is facilitated by a
protein carrier.
124. The thin segment is highly permeable to water and
moderately permeable to most solutes, including urea
and sodium.
125.
126.
127. Approximately 5 percent of the filtered
load of sodium chloride is reabsorbed
in the early distal tubule. The sodium-
chloride co-transporter moves sodium
chloride from the tubular lumen into
the cell, and the sodium-potassium
ATPase pump transports sodium out of
the cell across the basolateral
membrane. Chloride diffuses out of the
cell into the renal interstitial fluid
through chloride channels.
128. The principal cells reabsorb sodium and water
from the lumen and secrete potassium ions into
the lumen.
The intercalated cells reabsorb potassium ions
and secrete hydrogen ions into the tubular lumen.
both actions is increased by aldosterone.
. Antidiuretic hormone (ADH) causes
reabsorption of H2O. In the absence of ADH,
the principal cells are impermeable to H2O.
129.
130.
131. Chloride
• In the second half of the proximal tubule,
the higher chloride concentration favors
the diffusion of this ion from the tubule
lumen through the intercellular junctions
into the renal interstitial fluid. Smaller
amounts of chloride may also be
reabsorbed through specific chloride
channels in the proximal tubular cell
membrane.
132. 25% of the filtered loads of sodium, chloride, and potassium
are reabsorbed in the thick ascending limb of the loop of
Henle.
133. Potassium
• filtration rate = 756 mEq/day
• reabsorption rate = 644 mEq/day (87.8%)
– site -- proximal tubule and ascendong loop of
Henle
• secretion rate = 31 mEq/day
• excretion rate = 92 mEq/ day
134.
135.
136.
137.
138.
139.
140.
141.
142. Bicarbonate Reabsorption
• 90% HCO3
- reabsorption occurs in the
early proximal tubule by secondary active
transport (antiport) via the Na+ - H+
exchanger. 10-15% reabsorbed by DCT &
CT via a mechanism that involves the
exchange of Na+ for K+ or H+.
152. Urea Handling
(1) PCT
About 50% of the filtered urea is passively reabsorbed
The wall of PCT is partially permeable to urea but highly permeable to water so water
reabsorption from PCT → increases urea concentration in tubular lumen. This creates
concentration gradient → Urea reabsorption.
(2) Thick ascending limb of loop of Henle, DCT and cortical
collecting tubules
All are relatively impermeable to urea.
H2O reabsorbed in DCT and cortical collecting tubule (in presence
of ADH) increased urea concentration in tubular fluid.
(3) Inner medullary portion of the collecting duct
Urea diffuses into the medullary interstitium to increase its osmolality.
Diffusion of urea is facilitated by ADH.
40 - 60% of the tubular load of urea is excreted in urine.
►Urea cycle
• Urea moves from the medullary interstitium into the thin loop of
the Henle and back down into the medullary collecting
duct and again to medullary interstitium
several times before urea is excreted.
154. Subs Description Proximal tubule Loop of Henle Distal tubule Collecting duct
glucose
If glucose is not reabsorbed by
the kidney, it appears in the
urine, in a condition known as
glucosuria. This is associated
with diabetes mellitus..
reabsorption (almost
100%) via sodium-
glucose transport
proteins(apical)
and
GLUT(basolateral).
- - -
amino
acids Almost completely conserved. Reabsorption (active) - - -
urea Regulation of osmolality. Varies
with ADH
reabsorption (50%) via
passive transport secretion - reabsorption in
medullary ducts
sodium Uses Na-H antiport, Na-glucose
symport, sodium ion channels
reabsorption (65%,
isosmotic)
reabsorption
(25%, thick
ascending, Na-K-
2Cl symporter)
reabsorption
(5%, sodium-
chloride
symporter)
reabsorption
(5%, principal
cells), stimulated
by aldosterone
chloride
Usually follows sodium. Active
(transcellular) and passive
(paracellular)
Reabsorption
passive
reabsorption
(thin ascending,
thick ascending,
Na-K-2Cl
reabsorption
(sodium-
chlorid symp
-
water Uses aquaporin.
reabsorption
Passive-
60-70%
reabsorption
(descending)
5-10%
reabsorption
(with ADH,
via
vasopressin
receptor 2)
-
reabsorption
(with ADH, via
vasopressin
receptor 2)
HCO3
- Helps maintain acid-base
balance. [8]
reabsorption (80-90%)
[9]
reabsorption
(thick ascending)
[10]
-
reabsorption
(intercalated
cells,
H+ Uses [[vacuolar H+ATPase]] Secretion 85%- - Secretion
10%-
secretion
5%(intercalated
cells)
K+ Varies upon dietary needs. reabsorption (80%)
reabsorption
(20%, thick
ascending, Na-K-
2Cl symporter)
secretion increased by
aldosterone)
calcium reabsorption
reabsorption (thick
ascending) via
passive transport
reabsorption
stimulated
by PTH
-
phosp Excreted as titratable acid.
reabsorption (80%)
Inhibited by parathyroid - - -
155.
156. 156
Hormones acting on the kidney
1. Aldosterone:
• Stimulus for its secretion:
Blood volume (via renin-angiotentin system).
• Actions & their site:
It stimulates Na+ reabsorption in DCT & cortical CD
through:
1) In principal cells: Na+ reabsorption in exchange
with K+.
2) In -intercalated cells: Na+ reabsorption in
exchange with H+.
157. 2. Angiotensin II: It is the most powerful Na+ retaining
hormone.
• Stimulus for its secretion:
arterial bl. pressure & blood volume, e.g., hemorrhage (via
renin).
• Actions & their site:
1. It Na+ reabsorption by several mechanisms:
a. By stimulating aldosterone secretion.
b. In PCT: - By directly stimulating Na+-K+ ATPase at
basolateral border.
- By directly stimulating Na+-H+ countertransp. at
luminal border.
2. It constricts efferent arterioles.
158.
159. 159
3. Atrial Natriuretic Peptide (ANP): It facilitates NaCl & H2O
excretion.
• Stimulus for its secretion:
Atrial pressure (released from specific atrial fibers when
blood volume is )
• Actions & their site:
1. It GFR by VD of afferent & VC of efferent arteriole.
2. It Na+ reabsorption from DCT & cortical CD .
160. 4. ADH:
•Stimulus for its secretion:
Plasma osmolarity & blood volume.
•Actions & their site:
water reabsorption in late DCT, cortical & medullary
CD: by inserting aquaporin water channels into their luminal
membranes.
5. Parathormone (PTH):
•Stimulus for its secretion:
Plasma Ca2+ concentration.
•Actions & their site:
1. Ca2+ reabsorption from DCT.
2. Phosphate reabsorption from PCT.
161. Diuresis and diuretics
• Diuresis is defined as an increase in the urine flow rate;
• diuretics = agents that induce diuresis.
(A) H2O diuresis
Increase H2O intake decrease Osmotic. Pr inhibition of ADH
decrease facultative H2O reabsorption i.e. Urine large volume and
hypotonic.
(B) Osmotic diuresis
Unreabsorbable solute in PCT decrease obligatory H2O reabsorption
decrease Na+ concentration in tubular fluid decrease osmolarity
of medullary interstitium decrease facultative H2O reabsorption.
-Urine: large volume and isotonic or hypertonic.
(C) Pressure diuresis
Increase in arterial blood pressure leads to:
•↑ GFR.
•Inhibition of rennin angiotensin system → ↓ renin and angiotensin II
production.
•↑ Hydrostatic pressure in peritubular capillaries which → increase
Na+ & H2O excretion.
167. • In overhydration kidney produce diluted
urine hyposmotic to plasma.
• In dehydration kidney produce concentrated
urine hypersmotic to plasma.
• It is achieved by the countercurrent system.
• A countercurrent system is a system in
which the inflow runs parallel to, counter to,
and in close proximity to the outflow for some
distance. This occurs for both the loops of
Henle and the vasa recta in the renal
medulla.
168. • countercurrent system consists of-
Descending limb of the loop of Henle
Thin and thick portion of the ascending limb of the
loop of Henle
Medullary interstitium.
Distal convoluted tubule
Collecting ducts, and
Vasa recta
countercurrent system is feature of juxta medullary
nephron.
169. • The fundamental processes involved in excretion of
concentrated or diluted urine include-
1.Variable permeability of nephron- the descending limb of the
loop of Henle is highly permeable to water and relatively
impermeable to solute.
• The ascending loop of Henle-
• Thin segment is impermeable to water and permeable to
NaCl and urea.(passive reabsorption of NaCl)
• The thick segment loop of Henle is impermeable to water
and solute, but active reabsorption of Na+ by Na +-2Cl- -K +
Symporter and Na+ –k+ -ATPase pump.
• DCT is relatively impermeable to water.
• CD is permeable to water but impermeable to NaCl and
urea.
171. The concentrating mechanism depends upon the
maintenance of a gradient of increasing osmolality
along the medullary pyramids. This gradient is
-produced by the operation of the loops of Henle as
countercurrent multipliers and
-maintained by the operation of the vasa recta as
countercurrent exchangers.
Both together called countercurrent multiplier
exchanger system or countercurrent system.
173. 173
• Concentrated urine is also called hyperosmotic urine (urine
osmolarity > blood osmolarity).
• The kidney excretes excess solutes, but does not excrete
excess amounts of water.
• The basic requirements for forming a concentrated urine
are:
1. a high level of ADH, e.g., in water deprivation or
hemorrhage
permeability of late DCT & CDs to water, allowing these
segments to reabsorb a large amount of water.
2. a high osmolarity of the renal medullary interstitial fluid
provides the osmotic gradient necessary for water
reabsorption to occur in the presence of high levels of ADH.
• After passing to the interstitium, water is carried by the vasa
recta back into the blood.
174. The countercurrent mechanism depends on the
special anatomical arrangement of the loops of
Henle and the vasa recta. In the human, about 15%
of the nephrons are juxtamedullary nephrons, with
long loops of Henle and vasa recta that go deeply
into the medulla before returning to the cortex.
The osmolarity of the interstitial fluid in the medulla
of the kidney is much higher and may increase
progressively to about 1200 to 1400 mOsm/L in the
pelvic tip of the medulla. This means that the renal
medullary interstitium has accumulated solutes in
great excess of water.
175. The major factors that contribute to the buildup of
solute concentration high osmolarity (primarily NaCl
& urea) into the renal medulla are as follows:
Active transport of sodium ions and co-transport of
potassium, chloride, and other ions out of the thick
portion of the ascending limb of the loop of Henle into
the medullary interstitium.
Active transport of ions from the collecting ducts
into the medullary interstitium.
Facilitated diffusion of urea from the inner medullary
collecting ducts into the medullary interstitium.
Diffusion of only small amounts of water from the
medullary tubules into the medullary interstitium, far
less than the reabsorption of solutes into the
medullary interstitium.
180. Counter Current Multiplier
Descending limb (concentrating segment)
• Very permeable to H 2O.
• Much less permeable to NaCl and urea.
• Therefore, the tubular osmolarity gradually rises from
300 to 1200 mOsm/L
• Result; The interstitium fluid makes osmotic
equilibration with the descending limb .
181. ►Ascending limb
Thin segment
NaCl is passively reabsorbed into the medullary
interstitium .
Thick segment
It is absolutely impermeable to H 2O, but Na +, K+ and Cl- are
cotransported Actively into the renal medulla.
Result; The tubular fluid becomes hypotonic 100 mosm
as it enters the distal tubule and medullary interstitium
osmolarity gradually rises from 300 mOsm/L at
superficial layers of medulla and reaches 1200 mOsm/L
at deep layers of the medulla.
182. 182
How does the renal medulla become
hyperosmotic?
COUNTERCURRENT MULTIPLIER SYSTEM IN LOOP OF HENLE
183. • (step 1) Assume that the loop of Henle is filled with
fluid with a concentration of 300 mOsm/L, the same
as that leaving the proximal tubule.
• (step 2) the active ion pump of the thick ascending
limb on the loop of Henle reduces the concentration
inside the tubule and raises the interstitial
concentration; this pump establishes a 200-mOsm/L
concentration gradient between the tubular fluid and
the interstitial fluid.
• The limit to the gradient is about 200 mOsm/L
because paracellular diffusion of ions back into the
tubule eventually counterbalances transport of ions
out of the lumen when the 200-mOsm/L
concentration gradient is achieved.
184. (Step 3) is that the tubular fluid in the descending
limb of the loop of Henle and the interstitial fluid
quickly reach osmotic equilibrium because of
osmosis of water out of the descending limb. The
interstitial osmolarity is maintained at 400 mOsm/L
because of continued transport of ions out of the
thick ascending loop of Henle. Thus, by itself, the
active transport of sodium chloride out of the thick
ascending limb is capable of establishing only a
200-mOsm/L concentration gradient, much less than
that achieved by the countercurrent system.
(Step 4) is additional flow of fluid into the loop of
Henle from the proximal tubule, which causes the
hyperosmotic fluid previously formed in the
descending limb to flow into the ascending limb.
185. (step 5) Once this fluid is in the ascending limb,
additional ions are pumped into the interstitium, with
water remaining in the tubular fluid, until a 200-
mOsm/L osmotic gradient is established, with the
interstitial fluid osmolarity rising to 500 mOsm/L.
Then, once again, the fluid in the descending limb
reaches equilibrium with the hyperosmotic medullary
interstitial fluid (step 6), and as the hyperosmotic
tubular fluid from the descending limb of the loop of
Henle flows into the ascending limb, still more solute is
continuously pumped out of the tubules and deposited
into the medullary interstitium.
186. These steps are repeated over and over, with the net effect of
adding more and more solute to the medulla in excess of water;
with sufficient time, this process gradually traps solutes in the
medulla and multiplies the concentration gradient established by
the active pumping of ions out of the thick ascending loop of Henle,
eventually raising the interstitial fluid osmolarity to 1200 to 1400
mOsm/L (step 7).
Thus, the repetitive reabsorption of sodium chloride by the thick
ascending loop of Henle and continued inflow of new sodium
chloride from the proximal tubule into the loop of Henle is called the
countercurrent multiplier. The sodium chloride reabsorbed from the
ascending loop of Henle keeps adding to the newly arrived sodium
chloride, thus "multiplying" its concentration in the medullary
interstitium.
187. 187
PRODUCTION OF CONCENTRATED URINE
Reabsorption of Water in Presence of ADH:
-The tubular fluid reaching the late DCT is hyposmotic (100
mOsm/L).
Late DCT:- ADH the water permeability of the principal cells of
the late DCT.
Water is reabsorbed until the osmolarity of the DCT equals
that of surrounding interstitial fluid in renal cortex (300
mOsm/L).
CDs:
- ADH the water permeability of principal cells of CDs.
- As the tubular fluid flows through the CDs, it passes through
regions of increasing hyperosmolarity toward the inner medulla.
- Water is reabsorbed from the CDs until the osmolarity of the
tubular fluid equals that of the surrounding interstitial fluid.
The osmolarity of the final urine reaches 1200 mOsm/L.
188. N.B. The fact that large amounts of water are
reabsorbed into the cortex, rather than into the
medulla, helps to preserve the high medullary
interstitial fluid osmolarity.
Thus, in the presence of ADH, the fluid at the
end of CDs has the same osmolarity as the
medullary interstitium (1200 mOsm/L).
By reabsorbing as much water as possible,
the kidneys form a highly concentrated urine
while adding water back to ECF &
compensating for deficit of body water.
189. 189
Urea Recycling
• In the presence of ADH, urea contibutes 40% to the medullary
interstitial osmolarity (= 500 mOsm/L) by passive urea
reabsorption from the inner medullary CDs into the interstitium.
Mechanism:
- Ascending limb of loop of Henle, DCT, cortical CDs & outer
medullary CDs are impermeable to urea.
- As water is reabsorbed from late DCT, cortical & outer
medullary CDs, urea concentration rapidly.
- In inner medullary CDs, further water reabsorption takes place,
so that urea concentration rises even more. Thus, urea diffuses
out of the tubule into renal interstitium because this segment is
highly permeable to urea, and ADH increases this permeability
even more.
- A moderate share of the urea that moves into medullary
interstitium diffuses into thin descending limb of loop of Henle,
so that it passes again in tubular fluid. It recirculates several
times before it is excreted. Each time around it contributes to a
higher concentration of urea in interstitium.
Urea recirculation provides an additional mechanism for
forming a hyperosmotic medulla.
191. 191
THE COUNTERCURRENT SYSTEM
Vasa Recta as Countercurrent Exchanger
•Blood flow must be provided to the renal medulla to
supply the metabolic needs of the cells in this part of
the kidney. Without a special medullary blood flow
system, the solutes pumped into the renal medulla by
the countercurrent multiplier system would be rapidly
dissipated.
•There are 2 special features in medullary blood flow
that contribute to the preservation of the high solute
concentrations:
1. The medullary blood flow is low (only 1-2% of total
RBF) sufficient for metabolic needs of tissues, but
minimizes solute loss.
2. The vasa recta serve as countercurrent
exchangers, minimizing washout of solutes from the
medullary interstitium.
192. Vasa Recta as Countercurrent Exchanger
As blood descends into the medulla toward the
papillae, it becomes progressively more
concentrated, partly by solute entry from the
interstitium and partly by loss of water into the
interstitium. By the time the blood reaches the tips of
the vasa recta, it has a concentration of about 1200
mOsm/L, the same as that of the medullary
interstitium. As blood ascends back toward the
cortex, it becomes progressively less concentrated
as solutes diffuse back out into the medullary
interstitium and as water moves into the vasa recta.
blood leaving vasa recta is only slightly
hyperosmotic to normal plasma.
193. Countercurrent Exchange Mechanism:
Although there are large amounts of fluid and solute
exchange across the vasa recta, there is little net
dilution of the concentration of the interstitial fluid at
each level of the renal medulla because of the U
shape of the vasa recta capillaries, which act as
countercurrent exchangers. Thus, the vasa recta do
not create the medullary hyperosmolarity, but they do
prevent it from being dissipated.
Thus, the U-shape of vasa recta maintains the
concentration of solutes established by
countercurrent multiplier system.
198. Role of ADH
(a) Collecting tubule:
- ADH increase their permeability to H 2O so reabsorption of H 2O.
- Diffusion of urea is facilitated by ADH.
- Urea diffuses into the medullary interstitium to increase its
osmolality
(b) ADH slows the flow in vasa recta:
by acting on the efferent arterioles of the juxtamedullary nephrons.
This increases the medullary osmolality by decreasing washout of
the medullary solutes.
(c) ADH increase efferent arteriolar resistance:
of the juxtamedullary nephrons so increases their filtration, this
leading to more removal of sodium from the lumen of ascending
limb to the surrounding interstitial fluid, further, raises the
concentration of sodium ions in the medullary interstitium.
199.
200. 1- NaCl cycles:
NaCl is transported from ascending limb of both LH
& vasa recta to the interstitium. It then passively
diffuses into the descending limb of vasa recta (and
may be also slightly into descending limb of LH),
then is transported again from ascending limb and
so on.
2- Urea cycle:
First, it diffuses passively from medullary CD to the
interstitium from which it diffuses passively to
descending limb of vasa recta & LH, it is then
passively transported from ascending limb of vasa
recta and from medullary CD to the interstitium
again and so on.
202. Formation of Dilute Urine
• This will happen as long as antidiuretic hormone
(ADH) is not being secreted.
• Collecting ducts remain impermeable to water;
no further water reabsorption occurs.
• Sodium and selected ions can be removed by
active and passive mechanisms .
• Urine osmolality can be as low as 50 mOsm
(one-sixth that of plasma).
203. Formation of Concentrated Urine
• Antidiuretic hormone (ADH) inhibits diuresis.
• This equalizes the osmolality of the filtrate and
the interstitial fluid.
• In the presence of ADH, 99% of the water in
filtrate is reabsorbed.
• ADH-dependent water reabsorption is called
facultative water reabsorption.
• ADH is the signal to produce concentrated urine.
• The kidneys’ ability to respond depends upon
the high medullary osmotic gradient.
Urinary System: Late Filtrate Processing
205. Assessment if renal diluting and
concentrating ability
• Measurement of urine osmolality.
• Measurement of urine specific gravity.
• The urine concentration test.
• The urine dilution test.
• Estimation of free water clearance (CH2O)
206. Clinical disorders related to the concentration and
dilution of urine
• Primary psychogenic polydypsia (compulsive water drinking)
• Diabetes insipidus
• Central DI:
• Decreased ADH secretion due to lesion of posterior pituitary.
• Nephrogenic DI:
• Congenital defect in V 2 receptors in the collecting duct.
• Water deprivation
• Syndrome of inappropriate hypersecretion of antidiuretic hormone
(SIADH)
• Impairment of the countercurrent mechanism
• As in chronic renal failure → damage of renal medulla → the development of
hyperosmolality in medulla is poor → loss of concentrating power → iso-
osmotic urine (as that of plasma) 300mosmol. & fixed specific gravity.
208. 1
• pH = log -------- = - log (H+ )
[H+]
• H+ concentration [H+] is expressed in equivalents per
liter.
example, the normal [H+] is 40 nEq/L (0.00000004
Eq/L).
pH= - log (0.00000004)
• pH= 7.4
• Below pH (6.8) or above (8) death occur.
• Venous blood is acidic than arterial blood, because
acids are added to venous blood.
209.
210. • ACID
– a substance that can
donate or release
hydrogen ion (H+).
– Proton (H+) donor
– examples
• HCl (strong acid)
• H2SO4 (strong acid)
• H2CO3 (carbonic acid-
weak acid)
• H2PO4
• H3PO4
• BASE (ALKALI)
– a substance that can
combine with or accept
hydrogen ion (H+) .
– hydrogen acceptor
– examples
• OH- + (strong base)
• HCO3
-
• HPO4 2-
• H2 PO4
-
• Proteins (hemoglobin)
211. Sources of H+ ions in the body
• H+ is either ingested or produced each day by
metabolism.
• Complete metabolism of foodstuffs – produces CO2 in the form
of H2CO3 (carbonic acid ) ---- volatile acids
• Incomplete metabolism of CHO and fats – eg. lactic acid from
glucose; acetoacetic and - hydroxybutyric acid from fatty acid
oxidation ----- non -volatile acids
• Oxidation of proteins and amino acids – produces strong acids,
eg. H2SO4, HCl and H3PO4 (phosphoric acid) –--- non -
volatile acids
• H+ secreted by renal tubules each day .
216. The pK of the bicarbonate buffer system is 6.1.
217. 217
• Dibasic Phosphate buffer system
Na2HPO4 + H+ NaH2PO4 + Na+
–Most important intracellular buffer system.
The phosphate buffer system has a pK of 6.8.
–NaH2PO4 titratable acid.
H+ Na2HPO4
+
NaH2PO4
Click to
animate
Na+
+
218. Renal System
• third line of defense against acid – base
disturbances.
• acts over a period of hours to several days.
• Mainly remove non-carbonic acid.
• Sources of non-carbonic acid in the body are
cellular metabolism,exercise,uncontrolled
DM,starvation, high protein diet etc.
• remove excess H+ from the body in combination
with urinary buffers.
– excrete either acidic or alkaline urine.
219. 219
Factors affecting acid
(H+ secretion in the kidney)
1- PCO2: When PCO2 is high (respiratory acidosis), more
intracellular HCO 3
- is available and vice versa.
2- K+ concentration: When it increases, H+ secretion
decreases since both compete for secretion in DCT
& CCDs.
3- Carbonic Anhydrase: When carbonic Anhydrase is
inhibited, acid secretion is inhibited.
4- Aldosterone: enhances tubular reabsorbtion of Na +
and increases K+ and H+ secretion.
220.
221. 221
RENAL RESPONSE
• The kidney compensates for Acid - Base
imbalance within 24 hours and is responsible
for long term control.
• The kidney in response:
–To Acidosis
• Retains bicarbonate ions and eliminates
hydrogen ions.
–To Alkalosis
• Eliminates bicarbonate ions and retains
hydrogen ions.
222. 222
Renal regulation of pH
The kidney regulate pH by:-
1. Reabsorption of filtered HCO-
3.
2. Generation of new HCO-
3 .
3. Excretion of acid in the form of titrable acid and
ammonium ions.
All these mechanisms are accomplished through process
of H+ secretion by the nephron.
223. Acidification of the Urine
• Bicarbonate reabsorption
• Production of new bicarbonate
• Hydrogen secretion
– Acidifying urinary buffers
– Formation of NH3 to NH4
+
acidosis
↑
↑
↑
↑
alkalosis
↓
↓
↓
↓
↑ ↓
224. Sites of urine acidification
• Proximal tubule
– Na+H+ exchange mechanism
• Distal tubule (I cells)
– Aldosterone dependent ATP-driven pump
– H+K+ ATPase
• Collecting duct (I cells)
– Aldosterone dependent ATP-driven pump.
Main Sites of urine acidification are the DCT
and CT.
225. • The major buffer systems present in kidneys
are-
• Bicarbonate buffer system (24meq/L)
• Phosphate buffer system(1.5meq/L) and
• Ammonia buffer system
226. Fate of H+
• In proximal tubule the secreted H+ is buffered by
the filtered HCO-
3.
• The PCT is the major site where NaH2PO4
titratable acid is formed.
• In Distal tubule and Collecting duct the secreted H+
are buffered by Na2HPO4 and NH3 and are
excreted as titratable acid and ammonium ion
(NH4
+)
229. (1) active secretion of H+ into
the renal tubule; (2) tubular
reabsorption of HCO-
3 by
combination with H+ to form
carbonic acid, which
dissociates to form co2 and
H2O, and (3) sodium ion
reabsorption in exchange for
H+ secreted. The co2 formed
in the lumen from secreted
H+ returns to the tubular cell
to form another H+ and no
net H+ secretion occurs.
This pattern of H+ secretion
occurs in the proximal tubule,
the thick ascending segment
of the loop of Henle, and the
early distal tubule.
Bicarbonate system
233. Ammonia (NH3 ) System
Ammonia enters the tubular lumen not by filtration
but by tubular synthesis and secretion .
NH3 in the renal tubule is come from Glutamine
deamination
NH3 enter tubule by ways of diffusion or NH4 - Na+
antiport
The secretion of H+ may promote the secretion of
NH3
significance： promote the secretion of H+ and the
reabsorption of NaHCO3 , so play an important role
in keep the acid-base balance
235. 235
ACIDIFICATION OF URINE BY EXCRETION OF AMMONIA
Capillary Distal Tubule Cells
Tubular urine to
be excreted
NH2
H+
NH3
NH2
H+
NH3
WHAT
HAPPENS
NEXT?
236. 236
Capillary Distal Tubule Cells
Tubular Urine
NH3
Na+ Cl-
+
H2CO3
HCO3
- +
NaCl
NaHCO3
Click Mouse to
Start Animation
NaHCO3
NH3Cl-
H+
NH4Cl
Click Mouse to See
Animation Again
Notice the
H+ - Na+
exchange to
maintain
electrical
neutrality
ACIDIFICATION OF URINE BY EXCRETION OF AMMONIA
Dissociation of
carbonic acid
237. Medical Physiology by Guyton and Hall
Eleventh Edition
H+ SECRETION
AMMONIA IN THE PROXIMAL TUBULE
• Production and secretion of
ammonium ion (NH4
+) by
proximal tubular cells.
Glutamine is metabolized in
the cell, yielding NH4
+ and
bicarbonate. The NH4
+ is
secreted into the lumen by
a NH4
+ sodium-exchanger.
For each glutamine
molecule metabolized, two
NH4
+ are produced and
secreted and two HCO3
-
are returned to the blood.
238. Mechanisms of H+ excretion and HCO3
- generation.
A. Renal ammoniagenesis results in the formation of NH4
+ within cells because
NH3 readily combines with H+ at physiologic p H. NH4
+ is secreted via the Na/H
exchangers
239.
240. AMMONIA IN THE COLLECTING TUBULE
Medical Physiology by Guyton and Hall
Eleventh Edition
• Buffering of hydrogen ion
secretion by ammonia
(NH3) in the collecting
tubules. Ammonia diffuses
into the tubular lumen,
where it reacts with
secreted H+ to form
NH4
+ , which is then
excreted. For each
NH4
+ excreted, a new
HCO3
- is formed in the
tubular cells and returned
to the blood.
241.
242. Variation in pH of the tubular fluid
along the nephron
Schmidt, Human Physiology,1989
243. 243
ACIDOSIS / ALKALOSIS
• Acidosis
–A condition in which the blood has too
much acid (or too little base), frequently
resulting in a decrease in blood pH.
• Alkalosis
–A condition in which the blood has too
much base (or too little acid), occasionally
resulting in an increase in blood pH.
244. TYPES OF ACID – BASE DISORDERS
METABOLIC
ACIDOSIS
RESPIRATORY
ALKALOSIS
METABOLIC
ACIDOSIS
RESPIRATORY
ACIDOSIS
245.
246.
247.
248.
249. 249
ACIDOSIS
decreased
removal of
CO2 from
lungs
failure of
kidneys to
excrete
acids
metabolic
acid
production
of keto acids
absorption of
metabolic acids
from GI tract
prolonged
diarrhea
accumulation
of CO2 in blood
accumulation
of acid in blood
excessive loss
of NaHCO3
from blood
metabolic
acidosis
deep
vomiting
from
GI tract
kidney
disease
(uremia)
increase in
plasma H+
concentration
depression of
nervous system
accumulation
of CO2 in blood
accumulation
of acid in blood
excessive loss
of NaHCO3
from blood
respiratory
acidosis
254. 254
Anion Gap
• Definition
- It is the difference between the sum of the concentrations of the major
plasma cations and the major anions.
- The anion gap = [Na+ + K+ ] – [ Cl - + HCO3
- ].
• Normal value 16 mEq /L.
- Sometimes K+ is omitted from calculation and the anion gap = 12 m Eq/L.
• Importance
- In metabolic acidosis, serum HCO3- decreases.
- Thus, concentration of another anion must increase to maintain
electroneutrality.
- This anion can be chloride or other unmeasured anions.
• The anion gap is increased
- If concentration of other unmeasured anions is increased as in metabolic
acidosis due to renal failure, lactic acidosis and diabetic ketoacidosis.
• The anion gap is normal
- If concentration of chloride increased (hyperchloremic acidosis)
255. 255
• The anion gap will increase if
unmeasured anions are increased.
• The major un-measured anions are
albumin, phosphate, sulfate and other
organic acids.
• The plasma anion gap is used
clinically in diagnosing different
causes of metabolic acidosis.
258. Fates of secreted H+
1. 90% titrates filtered bicarbonate in a reclamation process
(H2CO3 ----- CO2 + H2O)
2. 1% is buffered by NH3 to form NH4+
3. 1 % is buffered by other tubular buffers mostly HPO42_
to form titratable acidity
4. a very minute amount of H+ remains free in the final urine
261. • The concept of clearance can be applied for
determination of-
• As a measure of GFR
• As a measure of secretory capacity
• As a measure of RPF & RBF
• As a measure of FF
• As a measure of osmotic & free water
clearance
• As a measure of excretion of waste products
262. As a measure of GFR
• Substance freely filtered, neither reabsorbed
nor secreted then the amount of the
substance excreted per minute would be
equal to the amount of substance filtered will
measure the GFR.
i.e. P x GFR = U x V
GFR= U x V/P =clearance
263. Clearance tests to measure GFR
Characteristics of an Ideal Marker
• Constant rate of production (or for exogenous marker
can be delivered IV at a constant rate).
• Freely filterable at the glomerulus (minimal protein
binding).
• No tubular reabsorption/secretion.
• No extra-renal elimination or metabolism.
• Availability of an accurate & reliable assay.
• For exogenous markers-- safe, convenient, readily
available, inexpensive & physiologically inert.
264. Various markers used :
A) Exogenous >>
• Inulin polysaccharide(gold standard )
• Non-radiolabelled contrast media (e.g. Iohexol)
• Radiolabelled compounds (e.g. 99m Tc-DTPA, Cobalt labelled
Vit B12, 51 Cr- labelled EDTA, Radio-iodine labelled hypaque)
• Mannitol
• Sorbitol
• Sucrose (i.V.)
B) Endogenous >>
1) Creatinine (marginally overestimates—most widely used in
clinical practice)
2) Urea ( not used at present)
265. Inulin clearance; Inulin has the following characteristics:
•Freely filtered i.e. plasma conc.= filtrate concentration.
•not reabsorbed or secreted by renal tubules
• i.e. amount filtered per min.= amount excreted in urine/min.
•Not metabolized.
•Not bound to plasma proteins.
•Not stored in the kidney.
•Does not affect filtration rate & its conc. is easily measured.
•Not toxic and biologically inert.
•Measurement of GFR with inulin is inconvenient because
inulin is not a normally occurring body substance and
266. Inulin clearance
A known amount of inulin is injected into the body. After
sometime, the concentration of inulin in plasma and
urine and the volume of urine excreted are estimated.
For example,
Concentration of inulin in urine = 125 mg/dL
Concentration of inulin in plasma = 1 mg/dL
Volume of urine output = 1 mL/min
Thus, Glomerular filtration rate = UV/P
= 125 × 1/1
= 125 ml/min
267.
268.
269. Creatinine clearance:
• Actually GFR is rarely measured clinically by inulin clearance.
Rather ,24-hour endogenous creatinine clearance is used.
Creatinine is a normal product of muscle metabolism.
• Creatinine is not an ideal substance for this purpose since it is
not only is filtered but also secreted to a small extent in the
human.
• The error introduced by this secretory component is about 10%
• Freely filtered
• Not reabsorbed
• partially secreted by renal tubules.
• Endogenous so used easily
• normal value of GFR by this method is approximately the same
as determined by inulin clearance.
270. Estimates of GFR
while creatinine
clearance is a
good estimate of
GFR,
plasma creatinine
is often used as a
clinical indicator
of GFR
271. Urea Clearance Test
clearance of urea from plasma by kidney every minute.
This test requires a blood sample to determine urea
level in blood and two urine sample collected at 1 hour
interval to determine the urea cleared by kidneys into
urine.Curea = Uurea X V/ Purea
Normal value of urea clearance is70 ml/min.
Urea is a waste product formed during protein
metabolism and excreted in urine. So, determination
of urea clearance forms a specific test to assess renal
function.
272. GFR=C No reabs, No Secret INULIN
GFR > C Much reabs, No Secret Gluc, AA, Na+,
Cl-
GFR < C No reabs, Much Secret PAH, Diodrast
273. Substances that are freely filtered but neither reabsorbed
nor secreted have renal clearance rate equal to GFR and
hence are called glomerular markers.
275. Substances that are freely filtered ,but are partially
reabsorbed in the tubules have renal clearance
rate less than GFR
• Urea (partially
reabsorbed)
• Urea Clearace <
125ml/min
276.
277. Substances that are freely filtered ,but are
completely reabsorbed have lowest clearance rate
• Sodium
• Glucose
• HCO3
• Amino acids
• Chloride
278.
279.
280. Substances that are filtered and also secreted by the
tubules, but not reabsorbed have the highest renal
clearance rate. Such substances are thus entirely exreted
by a single passage of blood through kidneys. Clearance of
such substances represent the range of blood flow.
• PAH=650ml/min
• Diodras
281.
282.
283. As a measure of secretory capacity
PAH is a substance that is:
• freely filtered by the glomeruli, not reabsorbed
secreted by PCT in the tubules
• 10% of PAH remain in blood, because 10% of the
PAH bound to plasma protein.
•The TmPAH is nearly constant, it is used clinically to
estimate tubular secretory capacity.
284. • Fitration load of PAH is a linear function of
plasma PAH ( P PAH) .But PAH secretion increases
as PPAH increases only until a TmPAH is reached.
The TmPAH is about 80 mg/dl .
• when P PAH is low, so that its concentration is kept
low in plasma , it is almost completely removed
with a single circulation of plasma in the kidneys.
• when PPAH is about 20 mg/dl, the secretory
mechanism become saturated and the TmPAH is
reached. At this point PAH secreted /min remain
constant and is independent of PPAH
• when the PPAH increases above TmPAH clearance of
PAH falls progressively and it becomes more a
function of glomerular filtration.
285.
286. Fick’s Principle
• amount of a substance taken up by kidney per unit
time is equal to the arterio-venous difference for the
substance across the organ times the blood flow.
RBF measured by Fick’s Principle.
Amount of substance removed per min= A-V
difference of substance X Flow
Amount of substance removed per min
Flow =
A-V difference of substance
287. 287
MEASUREMENT OF RENAL BLOOD FLOW
• Renal blood flow (RBF) is determined by measuring first
the renal plasma flow (RPF) and then calculating the RBF.
We measure RPF using (PAH) by intravenous (IV) infusion
• PAH is a substance that is:
• freely filtered by the glomeruli,
• Actively secreted
• It is not metabolized and not stored nor produced by the
kidney.
• It does no affect RBF.
• Its level can be measured easily.
• 90% is removed from the blood in a single circulation
• but not reabsorbed.
288.
289. •RPF can be measured by infusing (PAH) .
•PAH is filtered + secreted by the tubular cells,
•so extraction ratio (arterial concentration minus renal venous
concentration divided by arterial concentration) is high.
example, when PAH is infused at low doses, 90% of the PAH in
arterial blood is removed in a single circulation through the
kidney.
• It has therefore become common place to calculate the "renal
plasma flow" by dividing the amount of PAH in the urine by the
plasma PAH level, ignoring the level in renal venous blood.
• The value obtained should be called the effective renal
plasma flow (ERPF) to indicate that the level in renal venous
plasma was not measured. In humans, ERPF averages about
625 mL/min.
290. ERPF = UPAH x V/PPAH = Clearance PAH
• Example:
• Concentration of PAH in urine (UPAH): 14 mg/mL
• Urine flow (v): 0.9 mL/min
• Concentration of PAH in plasma (PPAH): 0.02 mg/mL
ERPF=14X0.9/0.02 =630 mL/min
ERPF can be converted to actual(true) renal plasma flow (RPF):
• Average PAH extraction ratio: 0.9
EPF/Excretion ratio = 630/0.9 =Actual RPF = 700 ml/min
• From the renal plasma flow, the renal blood flow can be
calculated by dividing by 1 minus the hematocrit:
• haematocrite value (Hct.) = 45%
• RBF = RPF x 1 / 1 – Hct = 700 x 1/55 =1273 ml/min
•
291. Osmotic clearance
• Cosm is the amount of water necessary to
excrete the osmotic load in a urine that is
isotonic with plasma.
• Cosm =UOsm v
Posm
Posm = Plasma osmolality
Uosm = urinary osmolality
V = rate of urine flow
292. • "Free Water Clearance" CH2O
• In order to quantitate the gain or loss of water by excretion of
a concentrated or dilute urine, the "free water clearance"
(CH2O) is sometimes calculated.
• CH2O =v- Cosm
• Cosm =UOsm v
Posm
• CH2O = v - UOsm v/ POsm
• CH2O is negative when the urine is hypertonic
• CH2O is positive when the urine is hypotonic.
• For example, the values for CH2O are –1.3 mL/min (–1.9 L/d)
during maximal antidiuresis and 14.5 mL/min (20.9 L/d) in
the absence of vasopressin.
293. Filteration Fraction (FF)
• Given that GFR is about 125ml/min and RPF is
about 650ml/min, only about @19% of the renal
plasma flow is actually filtered in to Bowman’s
space.
• FF= GFR/RPF = Cinu/CPAH
• RPF = GFR/FF
294. Uremia
When the breakdown products of protein metabolism
accumulate in the blood, the syndrome known as
uremia develops.
The symptoms of uremia –
lethargy, anorexia, nausea and vomiting, mental
deterioration and confusion, muscle twitching,
convulsions, and coma.
The blood urea nitrogen (BUN) and creatinine levels are
high, and the blood levels of these substances are used
as an index of the severity of the uremia. It probably is
not the accumulation of urea and creatinine per se but
rather the accumulation of other toxic substances—
possibly organic acids or phenols—that produces the
symptoms of uremia.
295. Causes
• 1. Acute renal failure (ARF)
• 2. Chronic or permanent renal failure.(CRF)
Treatment of renal failure
(1) Kidney transplants
(2) Dialysis
a) Artificial Kidney machine (haemodialysis).
b) Peritoneal Dialysis.
296. • Artificial kidney is the machine that is used
to carry out dialysis during renal failure.
• Dialysis is the procedure to remove waste
materials and toxic substances and to
restore normal volume and composition of
body fluid in severe renal failure. It is also
called hemodialysis.
297.
298. Basic Principles of Dialysis
• The basic principle of the artificial kidney is to pass
blood through minute blood channels bounded by a
thin membrane. On the other side of the membrane
is a dialyzing fluid into which unwanted substances
in the blood pass by diffusion.
• Artificial kidney in which blood flows continually
between two thin membranes of cellophane; outside
the membrane is a dialyzing fluid. The cellophane is
porous enough to allow the constituents of the
plasma, except the plasma proteins, to diffuse in
both directions-from plasma into the dialyzing fluid or
from the dialyzing fluid back into the plasma.
299. • The rate of movement of solute across the
dialyzing membrane depends on
(1) the concentration gradient of the solute between
the two solutions,
(2) the permeability of the membrane to the solute,
(3) the surface area of the membrane, and
4) the length of time that the blood and fluid remain
in contact with the membrane.
Thus, the maximum rate of solute transfer occurs
initially when the concentration gradient is
greatest (when dialysis is begun) and slows down
as the concentration gradient is dissipated.
300. • The total amount of blood in the artificial kidney at any
one time is usually less than 500 milliliters, the rate of
flow may be several hundred milliliters per minute, and
the total diffusion surface area is between 0.6 and 2.5
square meters. To prevent coagulation of the blood in
the artificial kidney, a small amount of heparin is
infused into the blood as it enters the artificial kidney.
• The artificial kidney cannot replace some of the other
functions of the kidneys, such as secretion of
erythropoietin, which is necessary for red blood cell
production. So anemia develop in CRF, and
secondary hyperparathyroidism due to 1,25-
dihydroxycholecalciferol deficiency.
301. • Dialyzing Fluid -The concentrations of ions Na+,
K+ ,HCO3
- and other substances in dialyzing
fluid are not the same as the concentrations in
normal plasma or in uremic plasma.
• There is no phosphate, urea, urate, sulfate, or
creatinine in the dialyzing fluid; however, these
are present in high concentrations in the uremic
blood. Therefore, when a uremic patient is
dialyzed, these substances are lost in large
quantities into the dialyzing fluid. the artificial
kidney is used for only 4 to 6 hours per day,
three times a week.
303. Paritoneal dialysis
• It uses the lining of person’s own abdominal cavity
(paritoneum) as a dialysis membrane. Dialyzing Fluid
is injected via a needle inserted through the
abdominal cavity and allowed to remain for hours
Dialyzing Fluid is then removed by reinserting the
needle and is replaced with new fluid.
• Peritoneal dialysis is a simple, convenient and less
expensive technique, compared to hemodialysis
• Procedure performed several times daily even at
home . Patient do normal activities simultaneously.
• It is less efficient in removing some of the toxic
substances and it may lead to complications by
infections.
305. • Micturition is the process by which the urinary
bladder empties when it becomes filled.
• 2 steps:
1) the bladder fills progressively until the tension in its
walls rises above a threshold level;
2) A nervous reflex called the micturition reflex that
empties the bladder or, if this fails, at least causes a
conscious desire to urinate.
Although the micturition reflex is an autonomic
spinal cord reflex, it can also be inhibited or
facilitated by centers in the cerebral cortex or
brain stem.
307. • Internal sphincter
• This sphincter is situated between neck of the
bladder and upper end of urethra. It is made
up of smooth muscle fibers and formed by
thickening of detrusor muscle. It is innervated
by autonomic nerve fibers. This sphincter
closes the urethra when bladder is emptied.
• External sphincter
• External sphincter is located in the urogenital
diaphragm. This sphincter is made up of
circular skeletal muscle fibers, which are
innervated by somatic nerve fibers.
308.
309. Nerve supply
1) Afferent
-From body, trigone & internal sphincter take double
route;
a) Along sympathetic nerve into L1,2
b ) Along parasympathetic nerve into S2,3,4
Function;
-Indicate degree of distension in the bladder.
-Convey pain sensibility.
310. Nerve On detrusor
muscle
On internal
sphincter
On external
sphincter
Function
Sympathetic
nerve via
presacral nerve
L1,2
Relaxation Contraction Not supplied Filling of urinary
bladder or
retention of urine
Parasympathetic
nerve via
Pelvic nerve or
nervus erigens.
s 2,3,4
Contraction Relaxation Not supplied Emptying of urinary
bladder
Somatic nerve via
pudendal nerve
Not supplied Not supplied Contraction Voluntary control of
micturition
EFFERENT NERVE SUPPLY TO URINARY BLADDER AND SPHINCTERS
311.
312.
313.
314.
315.
316.
317.
318.
319.
320.
321.
322.
323.
324.
325.
326.
327.
328.
329.
330.
331.
332.
333.
334.
335. cystometrogram
Definition
Cystometry is the technique used to study the
relationship between intravesical pressure and
volume of urine in the bladder.
Cystometrogram is the graphical registration
(recording) of pressure changes in urinary bladder in
relation to volume of urine collected in it.
Cystometric study uses a device to pump water into the
bladder. The device then measures the amount of
fluid present in the bladder when you first feel the
need to urinate, when you are able to sense fullness,
and when your bladder is completely full.
337. Components of cystometrogram
• Segment Ia –initial slight rise in pressure up to 10 cm of
H2O.
• Segment Ib – a long nearly flat segment due to intrinsic
tone of the bladder wall.
• Segment II – sudden rise in pressure > 100 cm of H2O --
+ micturition reflex--either micturition or a constant desire
to micturate.
• Superimposed on cystometrogram are periodic acute
rise in pressure called micturition waves which last few
seconds to more than a minute. These are the result of a
stretch reflex initiated by sensory stretch receptors in the
bladder wall.
• Micturition waves caused by the micturition reflex.
339. Law of Laplace
According to this law, the pressure in a spherical
organ is inversely proportional to its radius, the tone
remaining constant. That is, if radius is more, the
pressure is less and if radius is less the pressure is
more, provided the tone remains constant.
T
P = ------
R
Where, P = Pressure T = Tension R = Radius
Accordingly in the bladder, the tension increases
as the urine is filled. At the same time, the radius also
increases due to relaxation of detrusor muscle.
Because of this, the pressure does not change and
plateau appears in the graph.
340. Micturition Reflex
• As bladder fills sensory stretch receptors send
signals via pelvic nerves to sacral segments of
spinal cord.
• Parasympathetic stimulation of the bladder smooth
muscle via the same pelvic nerves occurs.
• It is “self-regenerative”, subsides, then re-
generates again until the external sphincter is
relaxed and urination can occur.
• The micturition reflex is a single complete cycle of -
(1) progressive and rapid increase of pressure,
(2) a period of sustained pressure, and
(3) return of the pressure to the basal tone of the
bladder.
341. micturition reflex
Afferent pathway
❶urine volume > 200-400 ml → bladder pressure↑
❷ → excites sensory stretch receptors in bladder wall(the
bladder feels "full" )
→conduct sensory signals by sensory nerve fiber of pelvic nerves
❸ → sacral micrurition centers(S2-S4) and brain-sensory area
desire to micturate.
Efferent pathway
Motor area-secral segment -
❹ → parasympathetic nerve fiber of pelvic nerves to the urinary
bladder wall
→the detrusor muscle contract and the internal urethral sphincter
relax
342. → urine enters posterior urethra
→ further excites sensory stretch receptors in
posterior urethra and bladder wall
→ further increase in reflex contraction of
bladder(self-regeneration, positive feedback)
❺ (meanwhile of ❹) → inhibit pudendal nerve
under voluntary control → the external urethral
sphincter diastole
❻ →emptying of bladder
343.
344. Voluntary Control of Micturition
1. Micturition reflex can be inhibited by:
a. midbrain
b. Cerebral cortex
2.Facilitatory centers for micturition- Pons
3. Voluntary contraction of external bladder sphincter
means emptying can be delayed even if a
micturition reflex occurs.
4. Voluntary emptying:
a. Contraction of abdominal muscles causes ↑
pressure in bladder
micturition reflex and inhibition of
external sphincter
b. Voluntary relaxation of external sphincter
345. Abnormalities of Micturition Three major types of
bladder dysfunction are due to neural lesions:
(1) interruption of the afferent nerves from the bladder
(Deafferentation)
(2) interruption of both afferent and efferent
nerves(Denervation)
(3) interruption of facilitatory and inhibitory pathways
descending from the brain.
In all types of bladder dysfunctions, it contracts,
insufficiently -- some urine is left in the bladder called
residual urine.
346. 1) Atonic Bladder and Incontinence
Caused by Destruction of Sensory Nerve
Fibers.
cause –
- crush injury to the sacral region of the spinal cord
- tabes dorsalis
- Person loses bladder control , bladder becomes
distended, thin-walled, and hypotonic. The
bladder fills to capacity and overflows a few drops
at a time through the urethra. This is called
overflow incontinence.
347. 2) Automatic Bladder Caused by Spinal Cord
Damage Above the Sacral Region .
• sacral cord segments are still intact, typical
micturition reflexes still occur. However, they
are no longer controlled by the brain.
( Micturition reflex is intact but uncontrolled.)
348. 3) Uninhibited Neurogenic Bladder
• results in frequent and relatively uncontrolled
micturition. This condition derives from partial
damage in the spinal cord or the brain stem that
interrupts most of the inhibitory signals.
Therefore, facilitative impulses passing
continually down the cord keep the sacral
centers so excitable that even a small quantity of
urine elicits an uncontrollable micturition reflex,
thereby promoting frequent urination.
349. 4) Interruption of both afferent and efferent
nerves(Denervation)
• injury
• complete loss of Voluntary micturition .
Bladder becomes flaccid & distended
called isolated or decentralized bladder.
350. Effects of Spinal Cord Transection
During spinal shock, the bladder is flaccid and
unresponsive. It becomes overfilled, and urine dribbles
through the sphincters (overflow incontinence). After
spinal shock has passed, the voiding reflex returns,
although there is, of course, no voluntary control and no
inhibition or facilitation from higher centers when the
spinal cord is transected. Some paraplegic patients train
themselves to initiate voiding by pinching or stroking their
thighs, provoking a mass reflex .
Spastic neurogenic bladder- the voiding reflex
becomes hyperactive, bladder capacity is reduced, and
the wall becomes hypertrophied. The reflex hyperactivity
is made worse by, and may be caused by, infection in the
bladder wall.
351. Nocturnal micturition (Bed wetting)
This is normal in infants and children below 3
years. It occurs due to incomplete myelination of
motor nerve fibers of the bladder resulting loss of
voluntary control of micturition .
352. Irritative Voiding Symptoms
• Urgency
– is the sudden desire to void
– in inflammatory conditions such as cystitis or in
hyperreflexic neuropathic conditions such as
neurogenic bladders resulting from UMN lesions.
• Dysuria
– painful urination
– associated with inflammation.
– The pain is typically referred to the tip of the penis
in men or to the urethra in women.
353. • Frequency
– is the increased number of voids during the
daytime, and
– nocturia is nocturnal frequency.
– Increased frequency may result from
increased urinary output or decreased
functional bladder capacity.
354. Renal disease
• Proteinuria
• loss of the ability to concentrate or dilute
the urine,
• uremia,
• acidosis, and
• abnormal retention of Na+
• Edema
• Hypertension
• Electrolyte imbalance
355. Proteinuria
• Permeability of the glomerular capillaries is
increased, and protein is found in the urine in
more than the usual trace amounts
(proteinuria).
• Most of this protein is albumin, and the
defect is commonly called albuminuria.
• Protein appear in urine in cases of long
standing position (orthostatic albuminuria).
356. Nephrotic Syndrome
• The amount of protein in the urine is very large.
• Excretion of Protein in the Urine Because of
Increased Glomerular Permeability .
• Any disease that increases the permeability of this
membrane can cause the nephrotic syndrome.
1. Chronic Glomerulonephritis,
2. Amyloidosis,
3. Minimal Change Nephrotic Syndrome
357. Loss of Concentrating & Diluting Ability
• Polyuria- The urine becomes less
concentrated and urine volume is increased.
• Oliguria- The urine becomes more
concentrated and urine volume is decreased.
358. Uremia
Uremia is the condition characterized by excess accumulation of
end products of protein metabolism such as urea, nitrogen and
creatinine in blood. There is also accumulation of some toxic
substances like organic acids and phenols. Uremia occurs
because of the failure of kidney to excrete the metabolic end
products and toxic substances.
Common features of uremia
• i. Anorexia (loss of appetite)
• ii. Lethargy
• iii. Drowsiness
• iv. Nausea and vomiting
• v. Pigmentation of skin
• vi. Muscular twitching, tetany and convulsion
• vii. Confusion and mental deterioration
• viii. Coma.
359. Acidosis
• Acidosis is common in chronic renal
disease because of failure to excrete the
acid products of digestion and metabolism.
• Renal tubular acidosis, there is specific
impairment of the ability to make the urine
acidic, and other renal functions are
usually normal.
360. Abnormal Na+ Handling
• Retention of excessive amounts of Na+ leads to edema.
• causes-
• Acute glomerulonephritis, a disease that affects
primarily the glomeruli, the amount of Na+ filtered is
decreased markedly.
• Nephrotic syndrome, The plasma protein level is low in
this condition, and so fluid moves from the plasma into the
interstitial spaces and the plasma volume falls. The decline
in plasma volume triggers the increase in aldosterone
secretion via the renin–angiotensin system. An increase in
aldosterone secretion contributes to the salt retention.
• Heart failure. Renal disease predisposes to heart failure,
partly because of the hypertension it frequently produces.
361. Renal Failure -Is a severe impairment in or a total lack
of renal function, which leads to disturbances in all
body systems.
• Classification According To Onset:
• Acute Renal Failure (ARF)
• Chronic Renal Failure (CRF)
ACUTE RENAL FAILURE
Acute renal failure is the abrupt or sudden stoppage of
renal functions. It is often reversible within few days to
few weeks. Acute renal failure may result in sudden
life-threatening reactions in the body with the
need for emergency treatment.
362. Causes of ARF
-Acute nephritis(inflammation of kidneys) - immune
complex
-Damage to renal tissue by poisons like lead, mercury &
carbon-tetrachloride
-Renal ischemia which is developed during circulatory
shock
-Acute tubular necrosis destruction of epithelial cells in
the tubules (caused by burns, hemorrhage, snakebite,
toxins (like insecticides, heavy metals and drugs)
-Severe transfusions reactions
-Sudden fall in B.P. during hemorrhage ,diarrhea ,severe
burn ,cholera
-Blockage of ureter due to formation of calculi (renal
stone) or tumor.
363. FEATURES
1. Oliguria (decreased urinary output)
2. Anuria (cessation of urine formation) in severe cases
3. Proteinuria (appearance of proteins in urine) including
albuminuria (excretion of albumin in urine)
4. Hematuria (presence of blood in urine)
5.Edema due to increased volume of extracellular fluid
(ECF) caused by retention of sodium and water
6. Hypertension within few days because of increased
ECF volume
7. Acidosis due to the retention of metabolic end products
8. Coma due to severe acidosis (if the patient is not treated
in time) resulting in death within 10 to 14 days.
364. Classification of ARF
Acute renal failure is often classified according to
location of the initial insult:
Prerenal
Before the kidneys; Blood ↓ flow to kidneys
Occurs in about 55-60% of all ARF cases
Intrarenal
Within the kidneys; actual damage to the filtering
structures of the kidneys.
Occurs in about 35-40% of all ARF cases
Postrenal
After the kidneys; obstruction of urinary excretion
Occurs in about 5% of all ARF cases
365. Prerenal ARF
-It occurs when renal blood flow is decreased before
reaching the kidney, causing ischemia of nephrons.
- Most common type of ARF
Causes:
- Hypotension (severe and abrupt)
- Hypovolemia
- Low Cardiac Output States
Treatment to correct cause, if not corrected it may
lead to permanent renal damage.
366. Intrarenal ARF
- It occurs when there is actual damage to the renal
tissue, resulting in malfunction of the nephrons.
Causes-
Glomerular Injury -Acute glomerulonephritis
Renal Interstitial Injury -Acute pyelonephritis
Tubular Epithelial Injury- Acute tubular necrosis (ATN)
Treatment: Immediate treatment to increase renal blood
flow and minimize damage. Not always reversible; may
lead to CRF.
367. Postrenal ARF
Occurs as a result of conditions that block urine flow
distal to kidneys, resulting in urine to backing-up into
the kidneys.
Causes
by a bilateral obstruction of the ureters or a bladder
outlet obstruction.
Calculi (stones)
Tumors or masses
Blood clots
Benign prostate hypertrophy (BPH)
Treatment -to correct cause, if not corrected it may
lead to permanent renal damage.
368. • CHRONIC RENAL FAILURE
Chronic renal failure is the progressive, long standing
• and irreversible impairment of renal functions.
When some of the nephrons loose the function, the
unaffected nephrons can compensate it. However,
when more and more nephrons start losing the
function over the months or years, the compensatory
mechanism fails and chronic renal failure develops.
• Vicious Cycle of Chronic Renal Failure Leading to
End-Stage Renal Disease. (ESRD) kidney leads to
progressive deterioration of kidney function and further
loss of nephrons .
370. Most Common Causes of End-Stage Renal Disease
(ESRD)
Cause Percentage of Total ESRD patients
Diabetes mellitus 45
Hypertension 27
Glomerulonephritis 8
Polycystic kidney disease 2
Other/unknown 18
371.
372. Specific Tubular Disorders
• Renal Glycosuria-Failure of the Kidneys to
Reabsorb Glucose.
• Aminoaciduria-Failure of the Kidneys to
Reabsorb Amino Acids
• Renal Hypophosphatemia-Failure of the
Kidneys to Reabsorb Phosphate.
• Renal Tubular Acidosis-Failure of the Tubules
to Secrete Hydrogen Ions.
• Nephrogenic Diabetes Insipidus-Failure of the
Kidneys to Respond to Antidiuretic Hormone .
373. • Fanconi's Syndrome-A Generalized
reabsorptive Defect of the Renal Tubules.
• Bartter's Syndrome-Decreased Sodium,
Chloride, and Potassium reabsorption in the
Loops of Henle .
• Gitelman's Syndrome - Decreased Sodium
Chloride reabsorption in the Distal Tubules.
• Liddle's Syndrome-Increased Sodium
reabsorption .
374. Glomerulonephritis
Abnormal immune reaction that damages the
glomeruli. In about 95 percent of the patients with
this disease, damage to the glomeruli occurs 1 to
3 weeks after an infection elsewhere in the body,
usually caused by certain types of group A beta
streptococci. It is not the infection itself that
damages the kidneys. Instead, over a few weeks,
as antibodies develop against the streptococcal
antigen, the antibodies and antigen react with
each other to form an insoluble immune complex
that becomes entrapped in the glomeruli,
especially in the basement membrane portion of
the glomeruli.
