Kidney Physiology

1
 The urinary system

By Silas Mkombe

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 Objectives

 COMPONENTS

 FUNCTIONS

 STRUCTURAL ADAPTATION TO

FUNCTION

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 Unit outline

• Introduction to urinary physiology

• Renal Function – The Main Elements
• Glomerular Filtration Rate (GFR) and Renal Blood
Flow (RBF)
• Urine Formation
• Fluid balance and Electrolyte Balance
• Acid-Base Balance
• Renal Function Tests and Pathophysiology of
Renal Disease

4
 Urinary physiology
 At the end of the lesson the learner should be
competent to: -
• Describe the basic anatomy of the organs of the
urinary system
• Describe the function(s) of the organs of the urinary
system
• Explain the process of urine formation and excretion
• Explain the pathophysiology of renal and urinary
diseases
• Explain the clinical implications of renal/urinary
diseases

5
 Introduction
• The principal function of the urinary system is to
regulate the volume and composition of body
fluids and excrete unwanted materials.
• The kidneys process blood and form urine as
waste products to be excreted.
• The urine formed collects continually in the
distensible urinary bladder
• Urine is then emptied periodically under the
control of the autonomic and somatic nervous
systems.
6
 Components of the urinary system

KIDNEYS

URETERS

URINARY BLADDER

URETHRA

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 The kidney

• Develops from the

lower end of the
mesonephric (Wollffian
duct) to the mid
vertebral column and
then ascend.
• The two kidneys make
0.5% of the total body
weight to weigh 125 –
170 gm each
• In adult males and 115
– 155 gm in females.

8
 Cont.
• The kidneys are paired, bean
shaped retroperitoneal
structures that lie on each side
of the vertebral column
• Extend from T12 to L3
vertebra.
• Each kidney has an average
size of 11 cm x 7 cm x 3 cm
equivalent to the size of a fist
• Covered by a largely non-
distensible fibrous capsule
which has a slit called the hilus
in the middle of the concave
side.

9
 SURFACE

POLE

HILUM

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 The hilus
• Port of entry of the renal
artery and nerves and an
exit site for the renal vein,
lymphatics and ureters.
• Opens into a shallow space
called the renal sinus
• The renal sinus includes
the renal pelvis (urine
filled space) and its
extensions (the major and
minor calyces).

11
 Functions of the kidney
a) Excretion of metabolic waste products and foreign
chemicals
b) Regulation of water and electrolyte balances
c) Regulation of body fluid osmolality and electrolyte
concentrations
d) Regulation of arterial pressure
e) Regulation of acid-base balance
f) Secretion, metabolism, and excretion of hormones
g) Gluconeogenesis
A) Excretion of Metabolic Waste Products, Foreign Chemicals, Drugs,
and Hormone Metabolites

• The kidneys are the primary means for eliminating waste

products of
metabolism
• These products include:
 urea(from the metabolism of amino acids)
 creatinine (from muscle creatine)
 uric acid (from nucleic acids)
 end products of hemoglobin breakdown (such as
bilirubin)
 metabolites of various hormones.
• The kidneys also eliminate most toxins and other foreign
substances such as pesticides, drugs, and food additives.
 B) Regulation of Water and Electrolyte Balances.

• For maintenance of homeostasis, excretion of

water and electrolytes must precisely match
intake.
• If intake exceeds excretion, the amount of that
substance in the body will increase.
• If intake is less than excretion, the amount of that
substance in the body will decrease.
• Intake of water and many electrolytes is governed
mainly by a person’s eating and drinking habits
• This requires the kidneys to adjust their excretion
rates to match the intake of various substances.
 C) Regulation of Arterial Pressure

• The kidneys play a dominant role in long-term

regulation of arterial pressure by excreting
variable amounts of sodium and water.
• The kidneys also contribute to short-term
arterial pressure regulation by secreting
vasoactive factors or substances, such as renin,
that lead to the formation of vasoactive prod-
ucts (e.g., angiotensin II).
 D) Regulation of Acid-Base Balance.

• The kidneys contribute to acid-base regulation,

along with the lungs and body fluid buffers, by
excreting acids and by regulating the body
fluid buffer stores.
• The kidneys are the only means of eliminating
from the body certain types of acids, such as
sulfuric acid and phosphoric acid, generated
by the metabolism of proteins.
 E) Regulation of Erythrocyte Production.

• The kidneys secrete erythropoietin, which

stimulates the production of red blood cells
• One important stimulus for erythropoietin
secretion by the kidneys is
hypoxia.
• The kidneys normally account for almost all the
erythropoietin secreted into the circulation.
• In people with severe kidney disease or who have
had their kidneys removed and have been placed
on hemodialysis, severe anemia develops
 F) Glucose Synthesis.

• The kidneys synthesize glucose from amino

acids and other precursors during prolonged
fasting, a process referred to as
gluconeogenesis.
• The kidneys’ capacity to add glucose to the
blood during prolonged periods of fasting
rivals that of the liver.
 Physiologic Anatomy
of the Kidneys
• Two kidneys lie on the
posterior wall of the abdomen
• Average weight is 150g
• surrounded by a tough, fibrous
capsule that protects its
delicate inner structures.
• The medial side of each kidney
contains an indented region
called the hilum
• Hilum passes the renal artery
and vein, lymphatics, nerve
supply, and ureter, which
carries the final urine from the
kidney to the bladder
• A dissection of a kidney will
give a medulla (Inner region)
and a cortex (outer region)
• The medulla is divided into
multiple 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
• The renal pelvis is 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
• Minor calyces collect urine from the tubules of each
papilla.
• The walls of the calyces, pelvis, and ureter contain
contractile elements that propel the urine toward the
bladder.
• From the bladder, urine is stored until it is emptied by
micturition
 Renal blood supply

• Blood flow to the two kidneys is normally about 22

per cent of the cardiac output
• The renal artery enters the kidney through the hilum
• It then branches progressively to form the interlobar
arteries, arcuate arteries, interlobular arteries (also
called radial arteries) and afferent arterioles
• The distal ends of the capillaries of each glomerulus
coalesce to form the efferent arteriole
• Efferent arteries lead to a second capillary network,
the peritubular capillaries, that surrounds the renal
tubules.
• The renal circulation is unique in that it has two
capillary beds, the glomerular and peritubular
capillaries
• They are arranged in series and separated by the
efferent arterioles, which help regulate the
hydrostatic pressure in both sets of capillaries.
• High hydrostatic pressure in the glomerular
capillaries (about
60 mm Hg) causes rapid fluid filtration
• The peritubular capillaries empty into the
vessels of the venous system
• The venous system run parallel to the arteriolar
vessels and progressively form the interlobular
vein,
arcuate vein, interlobar vein, and renal vein
• The renal vein leaves the kidney beside the
renal artery and ureter.
 The nephron
• It is the functional unit of
the kidney
• Each kidney in the human
contains about 1 million
nephrons, each capable of
forming urine.
• The kidney cannot
regenerate new nephrons.
• Therefore, with renal injury,
disease, or normal aging,
there is a gradual decrease
in nephron number.
• Each nephron contains:
1. A tuft of glomerular capillaries called the
glomerulus, through which large amounts of
fluid are filtered from the blood
2.A long tubule in which the filtered fluid is
converted into
urine on its way to the pelvis of the kidney
• The glomerulus is a
cluster of blood vessels
from which a filtrate
forms
• The tubule is an
epithelial structure
designed to convert
blood filtrate into urine.

27
• The two structures;
glomerulus and tubule
meet at the Bowman’s
capsule
• The Bowman’s capsule
surrounds the glomerulus
• It contains the Bowman’s
space.
• From the bowman’s space
that the filtrate passes into
the tubular system.

28
 Cortical and Juxtamedullary
Nephrons.
• Those nephrons that have glomeruli located in
the outer cortex are called cortical nephrons
• Cortical nephrons have short loops of Henle that
penetrate only a short distance into the medulla
• Nephrons that have glomeruli that lie deep in the
renal cortex near the medulla and are called
juxtamedullary nephrons.
• These nephrons have long loops of Henle that dip
deeply into the medulla
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 The Nephron

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 A.The renal corpuscle (glomerulus)

• Site of formation of the

glomerular filtrate.
• It is made up of:
1) the capillary tuft (vascular
elements which forms the
source of the filtrate)
2) Bowman’s space (where
the filtrate goes to)
3) Bowman’s capsule
(modified portion of the
proximal tubule).

32
• In a mature kidney the
glomerular capillaries
are covered by
podocytes
• Podocytes are modified
epithelial cells that
make up the visceral
layer of the Bowman’s
capsule

33
 Cont.
• Podocytes are continuous with the
parietal layer of the Bowman’s
capsule.
• The glomerular filtrate drains into
the Bowman’s space
• It then flows into the PT at the
urinary pole of the renal corpuscle.
• The glomerulus’s main function is
production of the glomerular
filtrate (GF)
• The filtrate passes into the PT
• PT has cells with long apical
microvilli well adapted for the main
function of reabsorption of solutes.

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 Glomerular Filtration
What gets filtered out at glomerulus?
– Water
– Glucose
– Ions/ Electrolytes (Na, Cl, K, Ca, Mg, P)
– Amino acids
– Bicarbonate, protons
– Wastes (creatinine, urea)
What doesn’t get filtered out at the glomerulus?

35
• Factors governing filtration rate at the
capillary bed are:
– Net filtration pressure
– Total membrane surface area available for
filtration (sympathetic control)
– Filtration membrane permeability
(podocytes)

36
 Glomerular Filtration Rate (GFR)
• Measurement of
functional capacity of the
kidney
• Dependent on difference
in pressures between
capillaries and Bowman’s
space
• Net filtration pressure
drives glomerular
filtration rate
• High pressure= high filt.
rate 37
Glomerular Filtration Barrier (GFB)

• The GFB between

glomerular turft of
capillaries and the
Bowman’s capsule
comprises of three
elements:
i. endothelial cells
ii. glomerular basement
membrane (GBM)
iii. A layer of epithelial
podocytes.

01/09/23 38
 I. Endothelial Cells

• Surrounded by the GBM and a layer of podocyte

foot processes except in a small area near the centre
of glomerulus where the endothelial cells come in
contact with mesangial cells (smooth muscle-like).
• The epithelial cells have large fenestrations (70 nm
holes)
• Fenestrations allow free movement of water, small
solutes and large molecules out of the capillary
lumen.

39
 II. Glomerular Basement Membrane (GBM)

• Is a 300 nm thick
structure located
between endothelial
cells and podocyte foot
processes.
• It separates the
endothelial layer from
the epithelial layer

40
 GBM…
• It is made up of three layers namely: -
– An inner thinner layer (lamina rara interna)
– Thick layer (lamina densa)
– An outer thinner layer (lamina rara externa)
• The GBM restricts filtration of intermediate large sized
solutes.
• The site is strongly anionic (negative charge) charges
due to sialic and dicarbxylic amino acids in the
basement membrane.
III. Podocytes
• Podocytes have processes that interdigitate and cover
the GBM.
01/09/23 41
 III. Podocytes

• Podocytes have
processes that
interdigitate and cover
the GBM

42
 Cont.
• The foot processes are
separated from each other
by filtration slits which are
connected by a slit
diaphragm with 4 – 14 µm
sized pores.
• Glycoproteins with negative
charges cover the podocytes,
filtration slits and slit
diaphragm.
• The charges at both the
basement membrane and
podocyte layers favouring of
positively charged solutes.

43
 2.The tubular system
Main functions
•Reabsorption
•Secretion
•Excretion

44
• The tubules account for the greatest amount of the
renal parenchyma
• Structure of renal tubule epithelium varies in different
parts of the nephron with regard to the functions.
Subdivisions
• The subdivisions of the tubular system include: -
– Epithelial elements – elements of the
Bowman’s capsule
– Proximal tubule (proximal convoluted tubule
(PCT) and proximal straight tubule (PST)

01/09/23 45
 –Loop of Henle (thin descending limb
(tDLH), thin ascending limb (tALH) and
thick ascending limb (TALH)
–Distal tubule - Early and late distal
–Collecting Ducts (initial Connecting
Duct (ICD), outer medullary collecting
tubule (OMCT) and inner medullary
collecting tubule (IMCT)

01/09/23 46
 Proximal tubule
• This is the second part of the
nephron and first part of the
renal tubule located in the
cortex.
• It is near the Bowman’s
capsule
• Follows a convoluted course
hence the name proximal
convoluted tubule though at
small section it is straight.
• The proximal tubule is a highly
specialized tubule with a single
layer of epithelial cells.

47
 Loop of henle

• This is the second part of

renal tubules found in the
medulla.
• It has three portions - thin
descending and ascending
limbs and the loop.
• The loop is lined by flat
epithelial cells.
• The descending and
ascending limbs of the loop
of Henle are less complex
with few mitochondria and
little membrane
amplification.

48
 Distal tubule

• Distal convoluted tubule which

begins at the macula densa
and end at transition of the
connecting tubule is shorter
than PCT
• Has less microvilli and several
of them drain into the
collecting duct, which drain
fluid from the cortex to the
medulla.
• It is lined by cuboidal cells and
contributes to urine
concentration.

01/09/23 49
 Connecting tubule

• The connecting tubule begins after the distal tubule

and ends at transition to initial collecting ducts.
• It has two types of cells namely the connecting
tubule cells and intercalated cells.
COLLECTING DUCT
• The collecting duct has two portions - the initial
collecting duct (runs up to the first confluence) and
the cortical (outer and inner) portion.

01/09/23 50
 Cells in Late Distal Tubule and
Collecting Duct That Regulate Balance
– Principal cells
• Water
• Electrolytes
– Intercalated cell
• Acid-base

51
 2. The ureter

• The ureter is a tube which

is about 28 cm long and
runs from each kidney to
the urinary bladder.
• The ureter conducts urine
from the kidney to the
bladder.
• The entry of the ureter
into the bladder is
guarded by a valvelike
narrow region that
prevents backflow from
the bladder.

01/09/23 52
 3. The bladder

• The urinary bladder is a collapsible bag located

behind the symphisis.
• It lies below the peritoneal peritoneum which
partially covers the superior surface of the
bladder.
• The bladder wall is made up mostly of smooth
muscle tissue (detrusor muscle).
• The bladder serves as a reservoir for urine and
expels urine from the body assisted by the
urethra.
53
 4. The urethra
• The urethra is a small
tube with mucous
membrane leading from
the floor of the bladder
(trigone) to the exterior
of the body.
• It lies directly behind the
symphysis pubis and
anterior to the vagina in
females where it extends
down and forward from
the bladder from a
distance of 3 cm.

01/09/23 54
 Urine formation

-The important functions of kidney is:

1) To discard the body waste that are either
ingested or produced by metabolism.
2) To control the volume and composition of body
fluids.

The functional unit of the kidney is the nephron which

is responsible for the formation of urine.
 The nephron
Each nephron has two major portions
1) Glomerulus (cluster of capillaries) [it is formed by a pair of
afferent and efferent arterioles surrounded by [Bowman′s
capsule].
2) Renal tubules
- which originates as a bulb called Bowman′s capsule.
The renal tubule is made up of:
i) Proximal (near) convoluted tubules
ii) loop of Henle (ascending and descending limb)
iii) Distal (far) convoluted tubule
iv) Collecting duct
 Cont.
• Urine is amber in colour due to the presence of
urobilin
• Urobilin a bile pigment altered in the intestines,
reabsorbed and excreted in the kidneys.
• Its specific gravity is 1.001 – 1.035.
• The daily urine production in a healthy adult is 1
– 1.5 litres
• The amount and specific gravity dependent on
fluid intake and amount of solutes excreted.

58
 Contents of urine
 Water (96%)
 urea (2%)
 Uric acid, creatinine, ammonia, sodium,
potassium, chlorides, phosphates, sulphates
and oxalates (2%)

59
 Mechanisms of renal excretion

• The basic mechanisms of renal excretion

involves
Filtration
Reabsorption
Secretion
Excretion
• Urine formation involves three processes
namely filtration, reabsorption and secretion.
60
 Formation of urine
The formation of urine involves three major
processes:
1) glomerular filtration, which takes place in
the renal corpuscles.
2) Tubular reabsorption which take place in
the renal tubules.
3) Tubular secretion which also take place in
the renal tubules.
 Glomerular Filtration

• The first step in urine formation

• Blood flows through the glomerulus, allowing protein-

free plasma to be filtered through the glomerular
capillaries into the Bowman’s capsule.

• ~20% of plasma entering the glomerulus is filtered

• 125 ml/min filtered fluid

62
 Glomerular Filtration
What gets filtered out at glomerulus?
– Water
– Glucose
– Ions/ Electrolytes (Na, Cl, K, Ca, Mg, P)
– Amino acids
– Bicarbonate, protons
– Wastes (creatinine, urea)
What doesn’t get filtered out at the glomerulus?

63
 Cont.
• Filtration depends on a pressure gradient between blood in
glomerulus and the filtrate in the Bowman’s capsule.
• Hydrostatic pressure of glomerular blood (HPG = 60 mmHg)
causes filtration out of the glomerular blood plasma into
the Bowman’s capsule.
• Capsular osmotic pressure (OPBC = 0 mmHg) is negligible.
• Osmotic pressure of glomerular blood (OPG = 32 mmHg)
• Hydrostatic pressure of the glomerular filtrate/capsular
filtrate (HPBC = 18 mmHg) oppose this direction of fluid
movement.

64
 Cont.
• Therefore,
• Effective Filtration Pressure (EFP)
= (HPG + OPBC) – (OPG + HPBC)
• = (60 + 0) – (32 + 18)
• = 60 – 50
= 10 mmHg
• Factors that favour rapid filtration are –
I. The presence of many fenestrae
II. The high glomerular hydrostatic pressure, which is
greater than tissue capillary pressure due to the
structural organization.
65
 Cont..
• The kidneys filter the body’s entire plasma volume 60
times each day.

• The filtrate:
– Contains all plasma components except protein
– Loses water, nutrients, and essential ions to become
urine

• The urine contains metabolic wastes and unneeded

substances

66
Filtration Surface
• The filtration surface is a three-layered structure
with a structural basis for selective sieving.
• The three structures are the :
I. endothelium with fenestrations (> 50 nm)
II. the GBM with 6 nm pores
III. channels in its glycoprotein structure and foot
processes of epithelial cells (podocytes) with 25
nm filtration slits.

67
The Renal Corpuscle
Foot process
of podocyte

Filtration slit
Pores in
endothelium

Basal lamina

Capillary
lumen
Filtered
material

Lumen of
Bowman’s
capsule

(d) Filtered substances pass

through endothelial pores
and filtration slits. 68
Figure 19-5d
 Cont.
• The three layers make the simple filtration
barrier.
• The glycoproteins of the GBM are strongly
negatively charged hence repel the negatively
charged proteins
• The endothelium has large fenestrae
• It is not an important protein barrier but the
basement membrane, which has a strong
negative charge curtsey of the presence of
glycoproteins in its structure prevents filtration of
proteins.
69
 Cont.
• The epithelial layer has podocytes or foot
processes separated by slit pores that allow
movement of the filtrate.
• Filtration of solutes is determined by their size
and electrical charge allowing selective filtration.
• Higher the molecular weight the lower the
filterability
• Negatively charged molecules are filtered less
easily than positively charged molecules of
similar molecular sizes.
70
 Cont.
GFR
• The glomerular filtration rate (GFR) is the
volume of filtrate produced per minute by
both kidneys
• Averages 125 mls per minute or 180 litres per
day, which is about 20% of the renal plasma
flow (GFR averages 115 mls/min in women
and 125 mls/min in males).

71
 Regulation of Glomerular Filtration
• Goal= regulate GFR
• If the GFR is too high:
– Needed substances
cannot be reabsorbed
quickly enough and are
lost in the urine
• If the GFR is too low:
– Everything is
reabsorbed, including
wastes that are normally
disposed of
72
Renal Autoregulation
• Renal autoregulation is the ability of the
kidneys to maintain a relatively constant GFR
when blood pressure is fluctuating and allows
precise control of renal excretion of water and
solutes.

73
74
 Cont.
• It is achieved via effects of locally produced
chemicals.
• When systemic arterial blood pressure falls to
70 mmHg afferent arterioles dilate and when
the pressure exceeds 160 mmHg they
constrict.
• Autoregulation is achieved through
tubuloglomerular feedback and myogenic
mechanisms.

75
 GFR Regulation
• Myogenic response
– Similar to autoregulation in other systemic
arterioles
• Tubuloglomerular feedback
– Involves Na+, K+, Cl-
• Hormones and autonomic neurons (NE/Epi)
– By changing resistance in arterioles
– By altering the filtration coefficient

76
Myogenic Autoregulation
• Goal is to keep GFR
constant!

BP GFR
aff. const GFR

BP GFR

aff. dial GFR

77
Tubuloglomerular
Mechanism
• Involve macula
densa cells in the
DCT
• MD cells are
sensitive to [Na+]

78
Tubuloglomerular
Tubuloglomerular Feedback
1 GFR increases.

Mechanism Efferent arteriole

Glomerulus Distal tubule

•If [Na
2 +
] isthrough
Flow high inincreases.
tubule DCT
GFR is too fast aff. art. Bowman’s capsule

constricts
3 Flow past macula densa increases.
Macula densa
4
1
5
•If [Na+] is low in DCT Granular cells

4 Paracrine from macula Afferent arteriole

GFR is densa
tootoslow aff. art.
afferent arteriole
3
2

vasodilates Proximal
5 tubule
Afferent arteriole constricts.

Resistance in afferent
arteriole increases.
Collecting
duct

Hydrostatic pressure
in glomerulus decreases.

Loop
of
GFR decreases. Henle
 ANS & Hormonal Regulation of GFR

Sympathetic NS (NE,
Epi) vasoconstricts
afferent arteriole

Angiotensin II
vasoconstricts afferent
arteroile

80
 Hormonal Regulation(RAAS)
Renin-Angiotensin-Aldosterone
System:

Renin is released from

juxtaglomerular apparatus when:
•Aff. art. MAP drops (JG cells don’t
stretch as much)
• Macula densa cells sense low
plasma osmolarity or low [Na+]
• Sympathetic NS input
What does renin do?

81
Renin-Angiotensin-Aldosterone System

RAAS animation
Reabsorption, Secretion, and
Excretion….

83
 2. Reabsorption

• Reabsorption is the
second step in urine
formation takes place
along the entire tubular
system (mostly in the
proximal tubules)
• Involves movement of
molecules out of the
tubule and into the
peritubular blood.
84
 Cont.
• Tubular reabsorption involves passive and
active transport of water and solutes at
different levels along the tubules.
• Water and solutes are transported via the:
 transcellular pathway (through the cell
membrane) or
 paracellular pathway (through the tight
junctions between cells).

85
• After absorption,water and solutes are
absorbed across the tubular epithelial cells
into the interstitial fluid
• They are transported through the peritubular
capillary walls into the blood by:
 bulk flow or
 ultrafiltration under the influence of
hydrostatic and colloid osmotic forces.

86
 Cont.
Active Transport
• Active transport requires energy which is derived from
metabolic processes to move solutes against an
electrochemical gradient.
• It can be primary active or secondary active transport
mechanisms.
 Primary active transport is directly associated to an
energy source for example hydrolysis of ATP.
• For the example the Na-KATPase pump functions
throughout the parts of the renal tubule producing the
energy needed for transport of sodium and potassium
ions.

87
 Cont.
 Secondary active transport has an indirect association to
an energy source implying that movement of substances
by this process depend on movement of another
substance that creates an ion gradient e.g. reabsorption
of glucose.
Passive transport
• Water is always reabsorbed by passive mechanisms
called osmosis
• Water diffuses from a region of low solute (high water
concentration) to that of a high solute concentration
(low water concentration).

88
 A. Proximal tubular reabsorption

• Highly supplied with mitochondria to support

active transport processes.
• Proximal tubules reabsorb sodium and major
ions.
• The proximal tubules have special characteristics
that allow its optimal function.
• These characteristics are: -
Highly metabolic epithelial cells
Many mitochondria

89
 Cont.
 Large surface area that allows rapid transport of
sodium and other solutes.
 Protein carrier molecules
• The proximal tubule is responsible for reabsorption of:
 Sodium
 Glucose
 Amino acids
 Chloride
 Phosphate
 Bicarbonate ions
01/09/23 Nmtc series Mocha Clifford. 90
Reabsorption, Secretion, Excretion
 B. Loop of henle

• The loop of Henle has

three functionally
distinct segments
namely:
• the thin descending
• thin ascending
• thick ascending
portions.

92
The descending thin segment is highly
permeable to water and moderately
permeable to solutes such as urea and sodium
hence it allows simple diffusion.
20% of water is reabsorbed from this
segment.

93
 Cont.
The TAS has thick epithelial cells with high
metabolic activity.
• The LOH allows reabsorption of 25% of sodium,
chloride and potassium and considerable
amounts of calcium, bicarbonates and
magnesium in this segment.
• The reabsorption of salt makes the tubule fluids
dilute and creates and maintains a high osmotic
pressure of the medulla’s interstitial Fluid.
01/09/23 94
 Cont.
C. Distal tubule
• The ascending loop of Henle empties its contents into
the DT.
• Its first portion forms part of the JGS that provides
feedback control of the GFR and renal blood flow.
• The next part of the distal tubule is highly convoluted
with reabsorptive characteristics as those of the thick
ascending segment of the loop of Henle.
• It facilitates rapid reabsorption of most ions sodium,
potassium and chloride
• Impermeable to water and urea hence it is refereed to
as the diluting segment because it dilutes tubular fluid.
95
D. Medullary collecting ducts
• This is the final site for processing urine and
determines the final urine output of water
and solutes.
• It reabsorbs less than 10% of sodium and
water.
• The ducts have cuboidal epithelial cells with
smooth surfaces and less mitochondria.

96
 Cont.
• Have special characteristics such as: -
Permeability to water controlled by ADH, high
ADH increases reabsorption and reduce urine
volume/concentrated
Permeable to urea – some urea is absorbed to
raise osmolality that enables the kidneys
concentrate urine
Secretes H+ against a large concentration
gradient – regulating acid-base balance
01/09/23 Nmtc series Mocha Clifford. 97
 Cont.
Regulation of tubular reabsorption
• Achieved through
Local mechanisms
Hormonal mechanisms
Nervous mechanism
1. Local Mechanisms
• Glomerular-tubular balance
•  Hydrostatic pressure and colloid osmotic
pressure and physical forces
• Arterial pressure and urine output
01/09/23 Nmtc series Mocha Clifford. 98
2. Hormonal
• Aldosterone
• Angiogenesis II
• Vasopressin (ADH)
• Parathyroid hormone
• ANP (Atrial Natriuretic Peptide)
3. Nervous
• Sympathetic nervous system constricts renal arteries reducing
sodium and water reabsorption reducing GFR
• Sympathetic nervous system increases reabsorption of sodium in
proximal tubule and thick ascending loop of Henle
• Release of renin and Angiogenesis II function

99
3. Tubular secretion
• Secretion is movement of molecules out of
the peritubular blood and into the tubule for
excretion.
• The proximal tubule is an important site in
secretion of organic acids and bases, which
are end products of metabolism as bile salts,
oxalates, urate and catecholamines that must
be removed from the body rapidly.

100
 Cont.
• The descending limb of the loop of Henle secretes urea
through diffusion.
• The distal tubule and collecting ducts secrete
potassium and hydrogen by active transport in
exchange for sodium and ammonium by passive
means.
• This is also the site for secretion of drugs and toxins.
• Drugs such as penicillin, salicylates and para-amino-
hipporic acid (PAH) are rapidly cleared and this may
affect their effective therapeutic concentrations.

101
102
 Cont.
• Potassium secretion increases when blood
aldosterone concentration increases.
• Aldosterone is a hormone produced by the
adrenal cortex
• It has effects on the distal tubule and
collecting duct cells
• Causes them to increases activity of the Na-K
pumps that move sodium out of the tubule
and potassium into the tubule.
103
 Urine concentration and dilution

• The kidney can generate urine which is as dilute as 30

mOsm (1/10 of plasma osmolality) or as concentred as
1200 mOsm (4 times plasma concentration).
• In a normal steady state, water intake and output must
be equal.
• The body’s three major sources of water are
(1)water consumed as a liquid (1400 mls)
(2)water contained within food that we eat (850 mls) and
(3)water produced by aerobic metabolism as
mitochondria convert food stuffs and oxygen to carbon
dioxide and water (350 mls).

104
Excretion
• This is the final step in renal excretion that
involves elimination of urine from the body
Urine storage and micturation
• Urine is formed continually by the kidneys and
passes through the ureters into the urinary
bladder where it is stored.

105
 Micturation

• Micturation or voiding is passage of urine

through voluntary relaxation of the external
sphincter.
• It is a process that is controlled by involuntary
and voluntary mechanisms.
• Parasympathetic fibres cause contraction of
the bladder and relaxation of the internal
sphincter.

106
 Cont.
• Involuntary mechanism responds to stretch
receptors and makes use of the spinal reflex
and reflex excitation of bladder.
• Micturation reflex is a single complete cycle of
progressive and rapid increase of pressure,
period of sustained pressure and release of
pressure to basal tone of the bladder.

107
 Cont.
Events of Micturation
– The urinary bladder becomes distended as it
fills with urine
– Stretch receptors in the bladder wall are
stimulated and the impulses are sent to the
micturation centre in the spinal cord.
– Parasympathetic nerve impulses travel to
the detrusor muscle and the internal
urethral sphincter

108
 Cont.
– The detrusor muscle contracts rhythmically,
and the internal urethral sphincter relaxes
– The need to urinate is sensed as urgent
– Urination is prevented by voluntary
contraction of the external urethral
sphincter and by inhibition of the
micturation impulses from the midbrain and
cerebral cortex.

01/09/23 109
 Cont.
– Following the decision to urinate, the
external urethral sphincter is relaxed, and
the micturation reflex is facilitated by
impulses from the pons and cerebral cortex.
– The detrusor muscle contracts and urine is
expelled through the urethra
– Neurones of the micturation reflex centre
are inactivated, the detrusor muscle relaxes,
and the bladder begins to fill with urine.

01/09/23 110
 Micturition
• The storage of urine and the micturition reflex
Higher
CNS
input
Relaxed Bladder
(filling) (smooth muscle)
state

Internal sphincter (smooth

muscle) passively contracted
Tonic
External sphincter (skeletal discharge
muscle) stays contracted
(a) Bladder at rest

111
Figure 19-18a
 Micturition

Stretch Higher CNS

Sensory neuron input may
receptors
facilitate or
inhibit reflex
1 Parasympathetic 1 Stretch receptors fire.
neuron
2

3 2 Parasympathetic neurons fire.

Motor neurons stop firing.

Motor neuron Smooth muscle contracts.

Tonic 3
Internal sphincter 2 discharge Internal sphincter passively
3 inhibited pulled open. External sphincter
External sphincter relaxes.
(b) Micturition

112
Figure 19-18b
 Micturition

Stretch Higher CNS

Sensory neuron input may
receptors
facilitate or
inhibit reflex
1 Parasympathetic 1 Stretch receptors fire.
neuron
2

2 Parasympathetic neurons fire.

Motor neurons stop firing.

Motor neuron
Tonic
Internal sphincter 2 discharge
inhibited
External sphincter

(b) Micturition

113
Figure 19-18b, steps 1–2
 Micturition

Stretch Higher CNS

Sensory neuron input may
receptors
facilitate or
inhibit reflex
1 Parasympathetic 1 Stretch receptors fire.
neuron
2

3 2 Parasympathetic neurons fire.

Motor neurons stop firing.

Motor neuron Smooth muscle contracts.

Tonic 3
Internal sphincter 2 discharge Internal sphincter passively
3 inhibited pulled open. External sphincter
External sphincter relaxes.
(b) Micturition

114
Figure 19-18b, steps 1–3
115
 Glucose Reabsorption
– Freely filtered at glomerulus
– Normally 100% actively reabsorbed
in proximal tubule
– Normally, no glucose appears in urine

116
 Glucose Reabsorption

– Carrier proteins for glucose reabsorption

• Apical membrane: secondary active transport
• Basolateral membrane: facilitated diffusion
117
Figure 18.15
Glucose Renal Curve

118
Figure 18.16
Reabsorption, Secretion, Excretion

120
 Cells in Late Distal Tubule and
Collecting Duct That Regulate Balance
– Principal cells
• Water
• Electrolytes
– Intercalated cell
• Acid-base

121
Distal Tubule Sodium Reabsorption

Coupled to the secretion of K+ and H+

122
Figure 19.13b
Effects of Aldosterone on Sodium
Reabsorption
– Aldosterone increases sodium reabsorption
– Steroid hormone
– Secreted from adrenal cortex
– Acts on principal cells of distal tubules and
collecting ducts
• Increases number of Na+/K+ pumps on basolateral
membrane
• Increases number of open Na+ and K+ channels on apical
membrane

123
 Potassium Balance
• Regulatory mechanisms keep plasma potassium in
narrow range
– Aldosterone plays a critical role
• Hypokalemia
– Muscle weakness and failure of respiratory muscles and
the heart
• Hyperkalemia
– Can lead to cardiac arrhythmias
• Causes include kidney disease, diarrhea, and diuretics

124
Effects of Aldosterone

125
Figure 19.14
Reabsorption, Secretion, Excretion

126
 Acid-Base Balance
– Normal pH of arterial blood = 7.35–7.45
• pH < 7.35 = acidosis
• pH > 7.45 = alkalosis
– Complications with acid-base disturbance
• Conformation change in protein structure
• Changes in excitability of neurons
• Changes in potassium balance
• Cardiac arrhythmias
• Vasodilation

127
Inputs and Outputs of Acid

128
Figure 19.23
Renal Handling of Hydrogen and
Bicarbonate Ions
– Proximal tubule
• Bicarbonate reabsorption coupled to hydrogen
ion secretion
– Distal tubule and collecting duct
• Secretion of hydrogen ions coupled to synthesis
of new bicarbonate ions

129
Bicarbonate Reabsorption

130
Figure 19.25
Hydrogen Ion Secretion

131
Figure 19.26
 Urine Concentration
Osmolarity changes as filtrate flows through the nephron
(from 300 mOsm/L to 100 mOsm/L)
Proximal Distal
tubule tubule

1 Isosmotic fluid leaving the

proximal tubule becomes
progressively more concentrated
in the descending limb.
300 mOsM CORTEX
300 100
300 mOsM MEDULLA
1 2 Removal of solute in the thick
ascending limb creates
3 Permeability to hyposmotic fluid.
water and solutes
2 Ions is regulated by
600 mOsM 3 Hormones control distal nephron
reabsorbed hormones.
but no permeability to water and solutes.
Only water water
reabsorbed
4 Urine osmolarity depends on
Variable reabsorption reabsorption in the collecting
of water and solutes duct.
900 mOsM
Loop
of
Henle

Collecting
1200
duct
1200 mOsM
4

50–1200 mOsM
urine excreted

132
Figure 20-4
133
Countercurrent exchange in the medulla of the kidney

134
 Countercurrent Exchange Animation

•http://www.colorado.edu/intphys/Class/
IPHY3430-200/countercurrent_ct.html

135
Water Reabsorption in Collecting Duct

No ADH

136
Figure 20-5b
with ADH

137
Figure 20-5a
Antidiuretic Hormone
Effects of ADH on Principal Cells

139
Figure 19.10
 Regulation of Blood Pressure

Figure 21–13 Short-Term and Long-Term Cardiovascular Responses

 Micturition
• The storage of urine and the micturition reflex
Higher
CNS
input
Relaxed Bladder
(filling) (smooth muscle)
state

Internal sphincter (smooth

muscle) passively contracted
Tonic
External sphincter (skeletal discharge
muscle) stays contracted
(a) Bladder at rest

141
Figure 19-18a
 Micturition

Stretch Higher CNS

Sensory neuron input may
receptors
facilitate or
inhibit reflex
1 Parasympathetic 1 Stretch receptors fire.
neuron
2

3 2 Parasympathetic neurons fire.

Motor neurons stop firing.

Motor neuron Smooth muscle contracts.

Tonic 3
Internal sphincter 2 discharge Internal sphincter passively
3 inhibited pulled open. External sphincter
External sphincter relaxes.
(b) Micturition

142
Figure 19-18b
 Micturition

Stretch
Sensory neuron
receptors

1 1 Stretch receptors fire.

Internal sphincter

External sphincter

(b) Micturition

143
Figure 19-18b, step 1
 Micturition

Stretch Higher CNS

Sensory neuron input may
receptors
facilitate or
inhibit reflex
1 Parasympathetic 1 Stretch receptors fire.
neuron
2

2 Parasympathetic neurons fire.

Motor neurons stop firing.

Motor neuron
Tonic
Internal sphincter 2 discharge
inhibited
External sphincter

(b) Micturition

144
Figure 19-18b, steps 1–2
 Micturition

Stretch Higher CNS

Sensory neuron input may
receptors
facilitate or
inhibit reflex
1 Parasympathetic 1 Stretch receptors fire.
neuron
2

3 2 Parasympathetic neurons fire.

Motor neurons stop firing.

Motor neuron Smooth muscle contracts.

Tonic 3
Internal sphincter 2 discharge Internal sphincter passively
3 inhibited pulled open. External sphincter
External sphincter relaxes.
(b) Micturition

145
Figure 19-18b, steps 1–3