Fluid Balance and Kidney Physiology

Formation and production of Urine

dr.Muhammad Ridwan, MAppSc, SpJP

 Major body fluid compartments

60%
intrac
40%
extracel
Ionic composition of the major body fluid compartments.
 Urinary System

• Two kidneys

• Two ureters

• Urethra
 Anatomy of Kidney

• Renal cortex: outer 1 cm

• Renal medulla: renal columns, pyramids - papilla
• Lobe of kidney: pyramid and it’s overlying cortex
Lobe of Kidney
 Excretion
• Separation of wastes from body fluids and
eliminating them
– respiratory system: CO2
– integumentary system: water, salts, lactic acid, urea
– digestive system: water, salts, CO2, lipids, bile
pigments, cholesterol
– urinary system: many metabolic wastes, toxins, drugs,
hormones, salts, H+ and water
 Kidney Functions
1. Filters blood plasma, eliminates waste, returns
useful chemicals to blood
2. Regulates blood volume and pressure
3. Regulates osmolarity of body fluids
4. Secretes renin, activates angiotensin, aldosterone
controls BP, electrolyte balance
5. Secretes erythropoietin, controls RBC count
6. Regulates PCO2 and acid base balance
7. Detoxifies free radicals and drugs
8. Gluconeogenesis
 Nitrogenous Wastes
• Urea
– proteinsamino acids NH2 removed
forms ammonia, liver converts to urea
• Uric acid
– nucleic acid catabolism
• Creatinine
– creatinine phosphate catabolism
• Renal failure
– azotemia: nitrogenous wastes in blood
– uremia: toxic effects as wastes accumulate
 Path of Blood Through Kidney
• Renal artery
 interlobar arteries (up renal columns, between lobes)
 arcuate arteries (over pyramids)
 interlobular arteries (up into cortex)
 afferent arterioles
 glomerulus (cluster of capillaries)
 efferent arterioles (near medulla  vasa recta)
 peritubular capillaries
 interlobular veins  arcuate veins  interlobar veins
• Renal vein
Blood Supply Diagram
Renal Corpuscle

Glomerular filtrate collects in capsular

space, flows into renal tubule
 Renal (Uriniferous) Tubule
• Proximal convoluted tubule
(PCT)
– longest, most coiled, simple
cuboidal with brush border
• Nephron loop - U shaped;
descending + ascending limbs
– thick segment (simple cuboidal)
initial part of descending limb
and part or all of ascending limb,
active transport of salts
– thin segment (simple squamous)
very water permeable
• Distal convoluted tubule (DCT)
– cuboidal, minimal microvilli
 Renal (Uriniferous) Tubule 2
• Juxtaglomerular apparatus: DCT,
afferent, efferent arterioles
• Collecting duct: several DCT’s join
• Flow of glomerular filtrate:
– glomerular capsule  PCT 
nephron loop  DCT  collecting
duct  papillary duct  minor calyx
 major calyx  renal pelvis 
ureter  urinary bladder  urethra
Nephron Diagram

• Peritubular
capillaries
shown only on
right
 Nephrons
• True proportions of nephron loops
to convoluted tubules shown
• Cortical nephrons (85%)
– short nephron loops
– efferent arterioles branch off
peritubular capillaries
• Juxtamedullary nephrons (15%)
– very long nephron loops, maintain
salt gradient, helps conserve water
– efferent arterioles branch off vasa
recta, blood supply for medulla
Urine Formation Preview
Filtration Membrane Diagram
Filtration Membrane
• Fenestrated endothelium
– 70-90nm pores exclude blood cells
• Basement membrane
– proteoglycan gel, negative charge
excludes molecules > 8nm
– blood plasma 7% protein,
glomerular filtrate 0.03%
• Filtration slits
– podocyte arms have pedicels with
negatively charged filtration slits,
allow particles < 3nm to pass
Filtration Pressure
 Glomerular Filtration Rate (GFR)
• Filtrate formed per minute
• Filtration coefficient (Kf) depends on permeability
and surface area of filtration barrier
• GFR = NFP x Kf  125 ml/min or 180 L/day
• 99% of filtrate reabsorbed, 1 to 2 L urine excreted
 Effects of GFR Abnormalities
• GFR, urine output rises  dehydration,
electrolyte depletion
• GFR  wastes reabsorbed (azotemia possible)
• GFR controlled by adjusting glomerular blood
pressure
– autoregulation
– sympathetic control
– hormonal mechanism: renin and angiotensin
Juxtaglomerular Apparatus

-Vasomotion
-Secrete renin

-monitor salinity
-Secret chemical vasocontrictor
 Regulation of GFR
• Intrinsic control (renal autoregulation)
• Neural control
• The renin angiotensin system
• Other factors
 Renal Autoregulation of GFR
• The myogenic mechanism
– Tendency of vascular smooth muscle to
contract when stretched and to dilate
when pressure decreases.
• Tubuloglomerular feedback
mechanism
– By macula densa cells
– When sensing increased flow or osmotic
signals MDC releases chemicals causing
vasocontriction of afferent arterioles
–  BP  constrict afferent arteriole,
dilate efferent
–  BP  dilate afferent arteriole,
constrict efferent
– Stable for BP range of 80 to 170 mmHg
(systolic)
– Cannot compensate for extreme BP
Role Macula Densa to Control GFR
 Sympathetic Control of GFR

• Strenuous exercise or acute conditions (circulatory

shock) stimulate afferent arterioles to constrict 
 GFR and urine production  redirecting blood
flow to heart, brain and skeletal muscles
• Sympathetic nervous system also stimulates JG
cells to release renin
Hormonal Control of GFR

-efferent arterioles
 Other factors controlling GFR
1. Prostaglandins (PGE2, PGI2  vasodilators)
2. Tromboxane  vasoconstrictor
3. Endothelium-derived relaxing factor (nitric
oxide)  vasodilator
4. Kallikrein  release bradykinin (vasodilator)
5. Adenosine  although as a systemic vasodilator,
it constricts renal vasculature
6. Endothelin  vasoconstrictor
Agents causing contraction or
relaxation of mesangial cells
 Mengukur GFR
• Menggunakan zat tertentu (dalam plasma)
• Ukuran molekul kecil
• Dapat difiltrasi di glomerulus
• Konsentrasi zat sama dengan plasma
• Tidak direasorbsi/tidak disekresi
• Terkumpul dalam urine (permenit)

• Jumlah zat yang difiltrasi permenit (tubular-load)

– GFR X Px = V X Ux
– GFR = (V X Ux) / Px

– Px = kadar zat dlm plasma

– Ux = kadar zat dlm urin
– V = kecepatan pembentukan urin
 Syarat Zat Untuk Mengukur GFR
• Bermolekul kecil
• Tidak direabsorbsi/disekresi
• Tidak mengalami metabolisme
• Tidak beracun
• Tidak terikat pada protein plasma
• Tidak disimpan dalam jaringan ginjal
• Tidak mempengaruhi kecepatan filtrasi
• Mudah dianalisa (plasma dan urine)
 Zat Tersebut Adalah:
• INULIN
– Suatu polimer dari fruktosa (BM 5200)

• MANITOL
– Suatu polisakarida

• Contoh:
– Uin = 29 mg/ml
– V = 1,1 ml/m
– Pin = 0,25 mg/ml

• GFR = (Uin X V)/Pin = (29 X 1,1)/0,25 = 128 ml/m

 Faktor Yang Mempengaruhi GFR
1. Perubahan tekanan hidrostatik dalam kapiler glomeruli
– Perubahan tekanan darah umum
– Vasokonstriksi/Vasodilatasi (v. afferen/v. efferen)
2. Perubahan tekanan hidrostatik dalam K. Bowman
– Obstruksi
– Edema jaringan ginjal
3. Perubahan tekanan koloid osmotik dari plasma
– Dehirasi
– Hipoproteinemia
4. Perubahan permeabilitas membran glomeruli
5. Perubahan luas area filtrasi
– Penyakit ginjal yang merusak glomeruli
– Nefrektomi partial
Estimated GFR
Tubular Reabsorption and Secretion
 Peritubular Capillaries
• Blood has unusually high COP here, and BHP is
only 8 mm Hg (or lower when constricted by
angiotensin II); this favors reabsorption
• Water absorbed by osmosis and carries other
solutes with it (solvent drag)
Proximal Convoluted Tubules (PCT)
• Reabsorbs 65% of GF to peritubular capillaries
• Great length, prominent microvilli and abundant
mitochondria for active transport
• Reabsorbs greater variety of chemicals than other
parts of nephron
– transcellular route - through epithelial cells of PCT
– paracellular route - between epithelial cells of PCT
• Transport maximum: when transport activity of plasma
membrane are saturated; e.g., if glucose > 220 mg/dL in
filtrate  appears in urine (glycosuria)
 Tubular Secretion of PCT
and Nephron Loop
• Waste removal
– urea, uric acid, bile salts, ammonia, catecholamines,
many drugs
• Acid-base balance
– secretion of hydrogen and bicarbonate ions regulates
pH of body fluids
• Primary function of nephron loop
– water conservation, also involved in electrolyte
reabsorption
 Osmolarity and osmosis
• Def: the number of solute particles dissolved in
one liter of water and is reflected in the solution’s
ability to cause osmosis.
• Osmotic activity is determined only by the number
of nonpenetrating solute particles and is
independent of their type and nature.
• 10 sodium ions have the same osmotic activity as
10 glucose molecules or 10 amino acids in the
same volume of solution.
 Osmolality vs Osmolarity
• Osmolality  when the concentration is expressed
as osmoles per kilogram of water
• Osmolarity  when it is expressed as osmoles per
liter of solution.
• In dilute solutions such as the body fluids, these
two terms can be used almost synonymously
because the differences are small.
• In most cases, it is easier to express body fluid
quantities in liters of fluid rather than in kilograms
of water.
 Countercurrent Multiplier
• Opposing activities of descending and ascending limb of Henle in order to
produce an osmotic gradient from cortex to the depth of medulla that allow
kidneys to vary urine concentration quite dramatically.
• Recaptures NaCl and returns it to renal medulla  increased osmolarity from 300
mosmol in cortex to about 1200 mosmol in the deepest part of medulla.
• Descending limb
– reabsorbs water but not salt
– concentrates tubular fluid
• Ascending limb
– reabsorbs Na+, K+, and Cl-
– maintains high osmolarity of renal medulla
– impermeable to water
– tubular fluid becomes hypotonic
• Recycling of urea: collecting duct-medulla
– urea accounts for 40% of high osmolarity of medulla
– Collecting ducts in deep medullary region are permeable to urea.
• In maintaining the osmotic gradients, vasa recta play important roles as the
countercurrent exchanger.
Countercurrent Multiplier
of Nephron Loop Diagram
 Countercurrent Exchange System
• Formed by vasa recta
• Provide blood supply to medulla
• Do not remove NaCl from medulla
• Descending capillaries
– water diffuses out of blood
– NaCl diffuses into blood
• Ascending capillaries
– water diffuses into blood
– NaCl diffuses out of blood
Maintenance of Osmolarity
in Renal Medulla
 DCT and Collecting Duct
• Mostly impermeable to water
• Reabsorption from this point on depends largely on
the needs of the body at the time and is regulated
by hormones (Aldosterone, ADH and ANF)
• In the absence of regulatory hormones, DCT and
Collecting duct are relatively impermeable to both
water and Natrium
• Aldosterone  Regulate Na and K ions
concentration
•  BP  causes angiotensin II formation
Action of mechanism of Vasopressin
Old name: ADH
 Dual control of
aldosteron secretion
Collecting Duct Concentrates Urine
• Osmolarity 4x as high
deep in medulla
• Medullary portion of
CD is permeable to
water but not to NaCl
 Summary of Tubular
Reabsorption and Secretion
Composition and Properties of Urine
• Appearance
– almost colorless to deep amber; yellow color due to
urochrome, from breakdown of hemoglobin (RBC’s)
• Odor - as it stands bacteria degrade urea to ammonia
• Specific gravity
– density of urine ranges from 1.000 -1.035
• Osmolarity - (blood - 300 mOsm/L) ranges from
50 mOsm/L to 1,200 mOsm/L in dehydrated person
• pH - range: 4.5 - 8.2, usually 6.0
• Chemical composition: 95% water, 5% solutes
– urea, NaCl, KCl, creatinine, uric acid
 Urine Volume
• Normal volume - 1 to 2 L/day
• Polyuria > 2L/day
• Oliguria < 500 mL/day
• Anuria - 0 to 100 mL
 Diuretics
• Effects
–  urine output
–  blood volume
• Uses
– hypertension and congestive heart failure
• Mechanisms of action
–  GFR
–  tubular reabsorption (Na+)  Natriuresis  diuresis
 Contoh diuretik
• Diuretik osmotik: ureum, manitol, dan sukrosa
• Lengkung diuretik: Furosemid, Asam etakrinat dan
Bumetanid
• Diuretik Tiazid: Hidroklorotiazid (HCT)
• Penghambat karbonik anhidrase: Asetazolamid
• Penghambat kompetitif aldosteron: Spironolakton
(Hemat Kalium)
• Pemblokir saluran Na: Amiloride, Triamterene