RENAL (URINARY) SYSTEM:

THE BIOCHEMICAL ASPECT (PART 1)

Abdul Salam M. Sofro

Faculty of Medicine
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 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
Normally1 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
Figure 44.13 Nitrogenous wastes

deamination
in Krebs Cycle
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
o Respiratory System
o CO2, Water
o Integumentary System
o Water, salts, lactic acid, urea
o Digestive System
o Water, salts, CO2, lipids, bile pigments,
cholesterol, etc.
o Urinary System
o 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)

Bowmans 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 - Bowmans capsule
Fluid filtered from glomerular
capillaries glomerular filtrate
Fluid is collected in capsular space
Fluid flows into renal tubule
www.lf3.cuni.cz/opencms/export/sites/.../jf_lecture_kidneys.pdf
 Glomerulus
Fenestrated capillaries
Capillary filtration in glomerulus
initiates urine production
Filtrate lacks cells & proteins
Drained by efferent arteriole
Peritubular capillaries
RENAL VEIN
 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 withinthe
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).
Terimakasih
Thank You