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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
•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)
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.)
•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)
•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:
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
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
• 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.)
• 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
•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: