RENAL (URINARY) SYSTEM:

the Biochemical aspect

Abdul Salam M. Sofro

YARSI University

http://www.indiana.edu/~nimsmsf/P215/p215notes/PPlectures/Printables/Kidney.pdf
Learning objectives
•By the end of lectures, students are expected to
understand:
•the role and function of renal and urinary
system in human
•the function of renal and urinary system in
homeostasis
•The production and composition of normal
urine from the perspective of Biochemistry
Introduction
 Kasus : Harus cuci darah teratur
Ibu M umur 53 th diantar suaminya ke RS karena badan lemah,
pusing dan muntah-muntah. Sejak 3 bulan terakhir merasa lesu
dan kurang bergairah tetapi diatasi dengan minum jamu atau
obat beli di warung. Saat ditanya dokter, suaminya mengatakan
kalau Ibu M sudah lama menderita kencing manis, sering
minum jamu dan obat sendiri bila tidak enak badan atau
pusing-pusing. Pada pemeriksaan fisik pasien tampak
menderita, pulmo & abdomen normal, jantung agak
membesar, nadi 98/mnt, Tensi 180/110 mmHg. Pemeriksaan
darah : Hb 10 g/dL, PCV 29%, Gula darah sewaktu 250 mg/dL,
BUN 90 mg/dL, creatinin 7 mg/dL. Oleh dokter pasien diminta
rawat inap di RS dan cuci darah (hemodialisis).
Renal insufficiency
•Extensive nephron destruction
•Kidneys unable to sustain homeostasis
 Azotemia, acidosis  uremia
•Causes
•Chronic kidney infections
•Trauma
•Heavy metal or solvent poisoning
•Hg, Pb, CCl4, etc.
•Renal tubule blockage
•Atherosclerosis, reduced blood flow to kidney
•Glomerulonephritis (autoimmune disease)
Renal insufficiency

•Treatment by hemodialysis
•Wastes artificially cleared from blood
•Blood pumped from radial artery to a dialysis
machine
•Heparin prevents clotting during process
•Wastes removed by simple diffusion
•Blood returned through a vein
•Typically 4 – 8 hours, 3x / week
Functional disorder of the Kidney
• Damage of the glomerulus

There are 3 different kinds of damage:

•Inflammation of the kidney causing damage to
the filter and a decrease of the flow through the
glomerulus
•Loss of charge of the membrane resulting in a
higher permeability for proteins
•Scar forming after inflammation causing loss of
functional tissue and filtering surface
Adaptations made by the kidney:
•Functional adaptation: loss of nephrons results in
a rise in blood pressure
Arteriole resistance in the glomerulus decreases
Qa (afferent arteriole flux) increases
Pgc (total filtration pressure) increases
fn (filtration fraction) increases
•Structural adaptation: hypertrophy of kidney
tissue resulting in an increase in filtering surface
•Kf (permeability * filtration capacity) remains the
same or decreases causing kidney insufficiency
 Signs of kidney problems

•Presence of protein or cells in urine may

indicate problems with glomerular filtration
•Presence of glucose may indicate problems
with tubular reabsorption or very high blood
sugar levels that present full resabsorption
RENAL FUNCTIONS
Role & Function of Kidney
•Renal & urinary systems are comprised of a
complex series of organs which together
function to:
•Filter wastes from the blood
•Manufacture, store and discharge urine
•These organ systems are vital to homeostasis
through maintaining:
•fluid balance,
•acid-base balance and
•blood pressure
The organs:
• Two kidneys
•Process plasma into
urine
• Two ureters
•Tubes that carry urine
to bladder
• A bladder
•Storage of urine
• An urethra
•Carries urine to
exterior
Facts about urine:
•Adults pass about a quart and a half of urine
each day, depending on the fluids and foods
consumed.
•The volume of urine formed at night is about
half that formed in the daytime.
•Normal urine is sterile. It contains fluids, salts
and waste products, but it is free of bacteria,
viruses and fungi.
•The tissues of the bladder are isolated from
urine and toxic substances by a coating that
discourages bacteria from attaching and
growing on the bladder wall.
URINALYSIS (Examination of physical &
chemical properties of urine) :

•Can determine physiological state of tissues

•Diagnostically valuable
•Various characteristics can be evaluated
•Properties evaluated:
•Appearance
•Odor
•Specific gravity
•Osmolarity
•pH
•Chemical composition
Urine Volume

•Normally 1 – 2 Liters per day

•> 2 Liters/day = Polyuria
•Causes : Fluid intake, Diabetes, Drugs
•< 500 mL/day = Oliguria
•Causes : Kidney diseases, Dehydration,
Circulatory shock, Prostate enlargement, etc.
•< 100 mL/day = Anuria  AZOTEMIA
•In Diabetes (many types):
•Chronic polyuria
•Generally due to high glucose
concentration in renal tubule  Result
from high glucose in Blood
•Osmotic reabsorption of water
inhibited
•Results in dehydration
•Diuretics (Chemicals that increase urine
volume)

•Mode of action:
•Increase glomerular filtration, e.g. Caffeine
dilates afferent arterioles
•Reduce tubular reabsorption, e.g.
•Ethanol inhibits ADH secretion
•Furosemide (Lasix) inhibits Sodium
reabsorption
Detail Renal function
•Function to regulate the volume and
composition of blood fluids by the excretion of
waste products and the modulation of salt and
water balance through the production of urine
•Eliminate waste products of metabolism &
foreign substances and their breakdown
products (removing metabolic waste except
CO2, e.g. ammonia, urea, uric acid & removing
foreign compounds, e.g. drugs, food additives,
pesticides)
 •Maintain extra-cellular fluid volume
through the regulation of body water
(regulating fluid volume)
•Control acid-base balance (regulating salt
concentrations and pH)

Blood volume & blood pressure are regulated.

Over 24 hrs – 180 L fluids : 1.5-2.0 L urine produced
Summary of Kidney Functions:

•Filter blood plasma, eliminate wastes -

products of metabolism
•Regulate blood volume, pressure
•Regulate fluid osmolarity
•Regulation of body water
•Detoxify free radicals, drugs & other foreign
substances
•Regulate pco2, acid-base balance
•Secrete renin
•Secrete erythropoietin (epo)- regulation of
erythropoiesis
•Synthesize calcitriol (vitamin D)-
metabolism of vitamin D
•Gluconeogenesis
Kidney & metabolic wastes

•Metabolism produces WASTES : especially

CO2 & nitrogenous wastes
•RESPIRATORY SYSTEM removes CO2
•URINARY SYSTEM removes both CO2 and
nitrogenous wastes
Nitrogenous wastes

A. Products of protein metabolism

•Proteins are broken down into amino acids (AA)
•AA are reassembled into proteins
•Excess AA is metabolized
•First step is removal of amino group
•Ammonia (NH3) is exceedingly toxic
•2NH3 + CO2 H2NC0NH2 (Urea)
•Urea is less toxic than ammonia.
•Urea comprises ~50% of nitrogenous wastes.
Nitrogenous wastes (cont.)

B. Products of nucleic acid metabolism

•Nucleic acids  Nucleotides
•Nitrogenous bases would be removed
•Some would be converted to uric acid
•Less toxic than ammonia
•Less abundant than urea
Nitrogenous wastes (cont.)

C. Products of Metabolism of Creatinine

phosphate
•Creatinine phosphate  Creatinine
•Less toxic than Ammonia
•Abundant than urea
Nitrogenous wastes

Renal failure
•Result in AZOTEMIA  Due to
accumulation of nitrogenous wastes in
blood
•Azotemia  UREMIA with many negative
effects such as diarrhea, vomiting etc. and
ultimately lethal.
Excretion
Removal of wastes
• Respiratory System
•CO2, water
• Integumentary System
•water, salts, lactic acid, urea
• Digestive System
•water, salts, CO2, lipids, bile pigments,
cholesterol, etc.
• Urinary System
•metabolic wastes, toxins, drugs, hormones,
salts, H+, water
Nephron
•Functional unit of the kidney
•1 million per kidney
•Smallest unit capable of forming urine
•Vascular component (conducts blood):
•Renal artery
•Afferent arteriole
•Glomerulus
•Peritubular capillaries
•Venules
•Renal vein
Nephron (cont.)

•Tubular component (forms urine)

•Bowman’s capsule
•Proximal Convoluted Tubule
•Loop of Henle
•Distal Convoluted Tubule
•Collecting duct
Blood vessels servicing kidney
• Renal artery supplies:
○ high blood flow. 1200 ml/min, or 21% of
the cardiac output, 94% to the cortex 
Afferent arterioles   Capillary cluster
(Glomerulus)
○ Two capillary beds
○ High hydrostatic pressure in glomerular
capillary (about 60 mmHg) and low
hydrostatic pressure in peritubular
capillaries (about 13 mmHg)
Renal Corpuscle

•Glomerulus & capsule

•Glomerulus enclosed in two-layered
glomerular capsule - “Bowman’s capsule”
•Fluid filtered from glomerular capillaries –
“glomerular filtrate ”
•Fluid is collected in capsular space
•Fluid flows into renal tubule
•Glomerulus

•Fenestrated capillaries
•Capillary filtration in glomerulus initiates
urine production
•Filtrate lacks cells & proteins
•Drained by efferent arteriole  Peritubular
capillaries     renal veins
Renal tubule
 Leads from glomerular
capsule
 Ends at tip of medullary
pyramid
 ~3 cm long
 Has four major regions:
○Proximal convoluted
tubule
○Nephron loop
○Distal convoluted tubule
○Collecting duct
•Proximal Convoluted Tubule (PCT)

•Arises from glomerular capsule

•Longest, most coiled region
•Prominent microvilli
•Function in absorption
•Much contact with peritubular capillaries
http://www.rosalindfranklin.edu/cms/anatomy/histohome/lectures/renal/01/index.html
http://www.rosalindfranklin.edu/cms/anatomy/histohome/lectures/renal/01/index.html
Relationships of the vascular
supply, the glomerulus and
the tubular components of
the nephron to each other
and the orientation of these
components within the renal
cortex and medulla
•Nephron loop (“Loop of Henle”)

•“U” – Shaped, distal to PCT

•Descending and ascending limbs
•Thick segments
•Active transport of salts
•High metabolism, many mitochondria
•Thin segments
•Permeable to water
•Low metabolism
•Distal Convoluted Tubule (DCT)

•Coiled, distal to nephron loop

•Shorter than PCT
•Less coiled than PCT
•Very few microvilli
•Contacts afferent and efferent arterioles
(regulation imparted)
•Contact with peritubular capillaries
•Collecting Duct

•DCTs of several nephrons empty into a

collecting duct
•Passes into medulla
•Several merge into papillary duct (~30 per
papilla)
•Drain into minor calyx
 The kidney receives roughly 20 percent of the
cardiac output, and 99 percent of this blood
flow goes to the renal cortex and one percent
to the renal medulla (Stewart, 1998).
The function of the renal tubules is to
reabsorb roughly 99 percent of the glomerular
filtrate, and the proximal tubule reabsorbs 60
percent of all the solutes in the glomerular
filtrate, including 100 percent of the glucose
and amino acids, 90 percent of the
bicarbonate and 80 percent to 90 percent of
the inorganic phosphate and water (Stewart,
1998).
URINE FORMATION
 Process of Urine formation

•Urine – water and waste solutes

•Nephron conduct 3 processes to convert blood
plasma into urine
•Filtration
•Filter blood plasma to retain cells/proteins
•Reabsorption
•Remove valuable materials from filtrate
•Secretion
•Transfer additional wastes to filtrate

& also water conservation

•Only about 1% of the glomerular fitrate
actually leaves the body because the rest (the
other 99%) is reabsorbed into the blood while
it passes through the renal tubules and ducts.
•This is called tubular reabsorption and occurs
via three mechanisms. They are:
•Osmosis
•Diffusion, and
•Active Transport.
http://www.rosalindfranklin.edu/cms/anatomy/histohome/lectures/renal/01/index.html
Filtration, reabsoption, and excretion rates of substances by the kidneys

Filtered Reabsorbed Excreted Reabsorbed

(meq/24h) (meq/24h) (meq/24h) (%)

Glucose (g/day) 180 180 0 100

Bicarbonate (meq/day) 4,320 4,318 2 > 99.9

Sodium (meq/day) 25,560 25,410 150 99.4
Chloride (meq/day) 19,440 19,260 180 99.1
Water (l/day) 169 167.5 1.5 99.1
Urea (g/day) 48 24 24 50
Creatinine (g/day) 1.8 0 1.8 0
 Filtration

•Occurs in the glomerulus

•Fenestrated capillaries
•3 layers of podocytes form
capillary walls
•Small pores (fenestrae)
•Filters plasma
•Proteins + cells stay in
blood
•Forms ultrafiltrate
•Filtration driven by blood
pressure
•Glomerular filtration is non
selective
•Small particles pass (glucose,
Na+, urea, H2O)
•Large ones do not
•20% of plasma enters tubule
•Plasma filtered 65x/day

Glomerulus is red; Bowman's

capsule is white.
Reabsorption
•Occurs in remainder of nephron tubule
•Selective movement of substances from
tubule into plasma
•Return of valuable substances to
peritubular caps
•Active or passive
•Passive (no energy)
•Active transport (requires energy)
Tubular reabsorption in PCT
What gets reabsorbed?
 Sodium, chloride, & other electrolytes
 Glucose
 Amino acids
 Water
 Protein
 Nitrogenous wastes
 Etc.
Proximal tubule
•Proximal tubule reabsorbs:
•2/3 of plasma Na+
•2/3 of plasma Cl-
•2/3 of plasma H2O
•100% of plasma glucose
Sodium (na+)
•Most abundant cation in filtrate
•Transcellular reabsorption
•Simple & facilitated diffusion into epithelial
cell (passive transport)
•From epithelial cell  ecf (active transport)
•Pericellular reabsorption
•Ecf  peritubular capillaries (passive)
•Sodium concentration gradient drives
reabsorption of other substances
•Glucose & Amino acids
•transcellular reabsorption
•sodium-glucose cotransport (active
transport)
•sodium-amino acid cotransport
(active transport)
•passive transport from epithelial cell
to extracellular fluid
•passive uptake by peritubular
capillaries
•Water
•tubular fluid hypotonic to intracellular and
extracellular fluids
•transcellular reabsorption
•passive transport
•pericellular reabsorption
•passive transport
•passive uptake by peritubular capillaries
•constant rate of water reabsorption
•modulated rates elsewhere in nephron
•Chloride (Cl-)
•transcellular and paracellular
reabsorption
•typically follows sodium ion (Na+)
•Other electrolytes
•K+, Mg+, Ca++
•paracellular & transcellular
reabsorption
•SO42-, PO42-, NO3-
•not reabsorbed
•Protein
•small amount in filtrate
•transcellular reabsorption
•enters epithelial cells via pinocytosis
(endocytosis)
•hydrolysis into amino acids
•passive transport of amino acids into
extracellular fluid
•passive uptake by peritubular capillaries
•Nitrogenous wastes
•urea
•passively reabsorbed with water
•~50% of urea reabsorbed (inadvertently)
•uric acid
•most reabsorbed
•(secreted later)
•creatinine
•not reabsorbed
•passive uptake by peritubular capillaries
Tubular reabsorption in nephron loop

•concentrate urine, conserve water

•reabsorb ~20% of water in filtrate
•thin segments
•passive transport
•thick segment impermeable to water
•reabsorb ~25% of na+, k+, cl-
•cotransport proteins in thick segments
•active transport
Tubular reabsorption in DCT

• concentrate urine, conserve water

• 36 liters/day enters DCT
• reabsorb water from filtrate
• reabsorb salts
• subject to hormonal control
• esp. aldosterone, antidiuretic hormone
(ADH), atrial natriuretic factor (ANF)
• PCT and nephron loop are not subject to
hormonal control
Secretion

• Also occurs in tubules

• Additional materials transported from plasma in peritubular
capillaries into tubule
•Excess K+, Ca2+ and H+, uric acid
•Foreign compounds
• By passive diffusion or active carrier transport
•Functions:
•waste removal
•esp. nitrogenous wastes, drugs
•acid-base balance
•secretion of H+, HCO3-
•regulation of pH of body fluids
Water conservation

•collecting duct
•receives from several nephrons
•reabsorbs H2O, concentrates urine
•begins isotonic to blood plasma
•becomes up to 4 times more concentrated
•concentration of urine dependent upon body’s
state of hydration
The substances that are secreted into the tubular
fluid (for removal from the body) include:

• Potassium ions (K+),

• Hydrogen ions (H+),
• Ammonium ions (NH4+),
• creatinine,
• urea,
• some hormones, and
• some drugs (e.g. penicillin).

Tubular secretion occurs from the epithelial cells that line the renal
tubules and collecting ducts.
The water, urea, and salts contained
within the ascending limb of Henle
eventually pass into the distal convoluted
tubule (DCT).
Active transport in the proximal tubule

• Na+ actively transported from cell to blood

• Creates Na+ gradient favoring Na+ flow from lumen
• Na+ gradient used to transport glucose against concentration gradient
(cotransport)
• Glucose diffuses into blood passively
www2.kumc.edu/ki/physiology/course/figures.htm
www2.kumc.edu/ki/physiology/course/figures.htm
www2.kumc.edu/ki/physiology/course/figures.htm
Passive re-absorption in the proximal
tubule

• Cl- to be reabsorbed passively along electrical gradient

• Water reabsorbed along osmotic gradient
www2.kumc.edu/ki/physiology/course/figures.htm
Acid Base Balance

• Proximal tubule also secretes H+ and absorbs HCO3-

•Used to regulate pH
•With  pH,  H+ secretion and HCO3-
reabsorption
www2.kumc.edu/ki/physiology/course/figures.htm
 Loop of Henle
• Kidneys produce a hyperosmotic urine
•Less H2O than blood plasma
•Concentrating mechanism occurs in the Loop of
Henle
•Countercurrent multiplication
•Generates osmotic gradient that draws H2O
out of the tubules to be reabsorbed
•Due to active reabsorption of Na+ & Cl-
The nephron and collecting duct: regional functions of the transport epithelium
n1.slideserve.com/PPTFiles/Ch44_89977_89654.ppt
Figure 44.23 How the human kidney concentrates urine in a juxtamedullary nephron in birds/ mammals.
Figure 44.23 How the human kidney concentrates urine: getting rid of solutes and conserving water

Impermeable
to water
Figure 44.23 How the human kidney concentrates urine: Urea and NaCl in the interstitial fluid outside of
nephron help reabsorb water from filtrate to make a hyperosmotic urine.
Loop of Henle

• Descending limb
•Permeable to water
•No active transport
• Ascending limb
•Impermeable to water
•Lined with Na+-K+ pumps

The Loop of henle is a counter current

multiplier, allowing the high concentrat
Loop of Henle

• Pumping of ions out of ascending limb creates osmotic gradient

• Water flows out of descending limb
• Absorbed by peritubular capillaries
• Fluid becomes more concentrated as it passes down descending limb
Loop of Henle

• Removal of ions without water causes fluid to become less

concentrated in the ascending limb
• Less concentrated than blood in distal convoluted tubule
• 25% of initial Na+ and water reabsorbed by loop of Henle
Unlike the descending limb, the ascending limb
of Henle’s loops impermeable to water, a
critical feature of the countercurrent exchange
mechanism employed by the loop. The
ascending limb actively pumps sodium out of
the filtrate, generating the hypertonic
interstitium that drives countercurrent
exchange. In passing through the ascending
limb, the filtrate grows hypotonic since it has
lost much of its sodium content. This hypotonic
filtrate is passed to the distal convoluted tubule
in the renal cortex.
 Distal Convoluted Tubule and Collecting Duct

• Secretion of K+ and H+
• Reabsorption of Na+ and water
• Generation of hyperosmotic urine
•Final ~8% of water and Na+ reabsorbed
www2.kumc.edu/ki/physiology/course/figures.htm
• As the urine travels down the collecting duct system, it passes by the
medullary interstitium which has a high sodium concentration as a result
of the loop of Henle's countercurrent multiplier system.
• Though the collecting duct is normally impermeable to water, it
becomes permeable in the presence of antidiuretic hormone (ADH).
ADH affects the function of aquaporins, resulting in the reabsorption of
water molecules as it passes through the collecting duct.
 Aquaporins are membrane proteins that
selectively conduct water molecules while
preventing the passage of ions and other
solutes. As much as three-fourths of the water
from urine can be reabsorbed as it leaves the
collecting duct by osmosis. Thus the levels of
ADH determine whether urine will be
concentrated or diluted. An increase in ADH is
an indication of dehydration, while water
sufficiency results in low ADH allowing for
diluted urine.
www2.kumc.edu/ki/physiology/course/figures.htm
• Lower portions of the collecting duct are also permeable to urea,
allowing some of it to enter the medulla of the kidney, thus
maintaining its high concentration (which is very important for the
nephron).

The water, urea, and salts contained within the ascending limb of Henle
eventually pass into the distal convoluted tubule (DCT).
Changes in permeability of collecting duct produce
concentrated or non-concentrated urine
Composition of urine
• Nitrogenous wastes
• From protein catabolism
• Urea, uric acid, ammonia, and creatinine.
• Electrolytes
• Sodium, potassium, ammonium, chloride, bicarbonate, phosphate, and
sulfate.
• Amount varies due to diet and other factors.
• Toxins
• Bacteria leaves the “body” in urea, thus the need to dilute the urine when
sick.
 Hormonal regulation of Reabsorption
• Aldosterone
• Increases Na+ reabsorption and K+ secretion by distal & collecting tubules
•  salt retention and BP (H2O retention)
• ADH
• Induces implantation of aquaporins (water channels) into tubule cell membranes
•  permeability of Distal and Collecting tubules to water
•  H2O reabsorption   urine volume
The amount of ADH in the blood may be
affected by conditions such as diabetes
insipidus, or by consumption of
diuretics* in the diet (*substances that
occur in some foods and drinks).
 Triggering of Aldosterone Release
• Release induces by juxtaglomerular apparatus
•Region of afferent arteriole that comes into
contact with ascending limb of Loop of Henle
• Releases renin (enzyme) into blood in response to  BP
• Renin converts angiotensinogen  angiotensin I
Triggering of Aldosterone Release (cont.)

• Angiotensin I converted to angiotensin II (fully activated) by angiotensin

converting enzyme in lungs
• Angiotensin II stimulates aldosterone release
 Urination

• Ureter
• Transfer urine to pelvic region
• Urinary Bladder
• Stores urine
• Smooth muscles, stretchable walls
• Two sphincters
• Internal urethral sphincter (involuntary)
• External urethral sphincter (voluntary)
Ureters
• Carry urine from kidneys to urinary bladder via
peristalsis
• Rhythmic contraction of smooth muscle
• Enter bladder from below
• Pressure from full bladder compresses ureters
and prevents backflow
• Small diameter
• Easily obstructed or injured by kidney stones
(renal calculi)
Urinary bladder

• Muscular sac
• Wrinkles termed rugae
• Openings of ureters common site for bladder infection
Urethra

•Conveys urine from body

•Internal urethral sphincter
•Retains urine in bladder
•Smooth muscle, involuntary
•External urethral sphincter
•Provides voluntary control over voiding
of urine
Urethra (cont.)

• ~18 cm long in males

• Prostatic urethra
• ~2.5 cm long, urinary bladder  prostate
• Membranous urethra
• ~0.5 cm, passes through floor of pelvic
cavity
• Penile urethra
• ~15 cm long, passes through penis
Urethra (cont.)

•3 – 4 cm long in females
•Bound by connective tissue to anterior wall
of vagina
•Urethral orifice exits body between vaginal
orifice and clitoris
 Urination (Micturition) / Urination Reflex:

• ~200 ml of urine held

• Distension initiates desire to void Stretch receptors
in bladder wall  spinal cord
• Efferents to smooth muscles  contraction
• Internal sphincter relaxes involuntarily
• Smooth muscle
• External sphincter voluntarily relaxes
• Skeletal muscle
• Poor control in infants
• Bladder muscle contracts
• Urine forced through urethra