Renal & Body Fluids Module: PHYSIOLOGY OF THE UROPOIETIC SYSTEM

Minarma Siagian Bagian Ilmu Faal IKDU-FKUI

Why?

Overview of functions
Regulation of body fluid osmolality & volume:

Excretion of water and NaCl is regulated interacting with CV, endocrine, CNS

Regulation of electrolyte balance:

Daily intake of inorganic ions (Na+, K+, Cl-, HCO3-, H+, Ca2+, Mg+ & PO43-) should be matched by daily excretion through kidneys.
Kidneys work in concert with lungs to regulate the pH in a narrow limits of buffers within body fluids.

Regulation of acid-base balance:

Overview of functions
Excretion of metabolic products & foreign

substances:

urea from amino acid metabolism uric acid from nucleic acids creatinine from muscles end products of hemoglobin metabolism hormone metabolites foreign substances (e.g., drugs, pesticides, & other chemicals ingested in the food)

Overview of functions
Production and secretion of hormones: renin (activates the renin-angiotensin-aldosterone system, thus regulating blood pressure & Na,K balance) prostaglandins/kinins (bradykinin = vasoactive, leading to modulation of renal blood flow & along with angiotensin II affect the systemic blood flow) 1,25-dihydroxyvitamin D3 (stimulates Ca2+ resorption & bone deposit) erythropoietin (stimulates red blood cell formation by bone marrow).

STRUCTURE
MACROSCOPIC

MICROSCOPIC
Funtional unit : NEPHRON Cortical nephron Juxtamedullary nephron Glomerulus (Bowman caps. + glomerular capillary) Tubules (Proximal T. + Loop of Henle + Distal T. ) Collecting Ducts Juxtaglomerular apparatus Afferent + efferent arterioles Peritubular capillary - vasa recta

Cortex Medulla

NEPHRON

Structure of Tubular Cells

Juxtaglomerular Apparatus

Renal Vascularization
Abd Ao renal a interlobar a arcuate a interlobular a (cort radial a) afferent ale glomerular cap afferent ale peritubule kap (vasa recta) venules veins renal v IVC RA
How does this system affect PGC?

Autoregulation
local & fast regulation of afferent/efferent

ale :

miogenic Tubuloglomerular feedback Not complete Not effective if BP < 70 or > 200 mmHg RPF can still change through sympathetic control or A II

only effective within a certain range

Autoregulation
1.5

Range of autoregulation

RPF (L/min) 1.0

0.5

40

80

120

160

200

240 (mmHg)

 renal press. P GC GFR renal a press.

flow thru prox tub & AH

distal delivery of fluid (macula densa) [Na] in mac densa secr vasoconst (?) by JGA to aff ale constr aff ale

TUBULOGLOMERULAR FEEDBACK

Three general processes determine the composition and volume of urine:

1. Glomerular filtration (cf. renal clearance) 2. Reabsorption of the substance from the tubular fluid into blood 3. Secretion of the substance from the blood into the tubular fluid

Glomerular Filtration
Plasma in glomerular cap Glomerular Membrane

Ultrafiltrate ( plasma protein) Membran Filtrasi:

Endothelial cells of glomerular cap (fenestra, mesangial cells) Lamina basalis (extracell matrix - glikoprotein negatively charged) Epithelial cells of Bowmans caps (podocytes - filtration slits)

Affected by: Filtration Pressure Filtration surface area Permeability of filtration membrane

sel mesangial

FILTRATION

Glomerular Filtration
Systemic blood vessels:

artery capillary vein Renal vessels portal system: afferent ale capillary efferent ale PGC (BP) maintained high afferent ale > efferent ale Filtration without reabsorption

. Filtration

capillary

arteriole

venule

Filtration
PCap
Filtr press filtr reabsorb

capillary

arteriole

venule

Glomerular Filtration

glom cap

afferent ale

efferent ale

Glomerular Filtration
PGC
Filtr press Filtration

glom cap

afferent ale

efferent ale

Forces Involved in Glomerular Filtration

Glomerular Capillary Blood Pressure

Plasma Colloid Osmotic Pressure

+ -

55

30 Bowmans Capsule Hydrostatic Pressure

15

Net Filtration Pressure

10

Hydrostatic Pressure (P) and Oncotic Pressure () in glomerular capillary

60

40 P (mmHg) 20

0 0 glomerular cap 1

Glomerular Filtration
FILTRATION PRESSURE (STARLING FORCES)
Drives filtration:

Glom cap hydrostatic pressure (PGC) Bowmans caps oncotic pressure (BC = 0) Bowmans caps hydrostatic pressure (PBC) Glom cap oncotic pressure ( GC)

Against filtration:

Net Fitration Pressure = [PGC PBC]- [GC - GC

Glomerular Filtration
Mesangial cell contraction
Angiotensin

> 50x capillary in muscle

Filtration slit

Kf
(filtration coefficient)

Glomerular Filtration Rate

Volume of plasma (ml) going through the glomerulus (filtered) each minute

GFR = Kf (PGC - PBC - GC)

Intrinsic control (AUTOREGULATION) miogenic tubuloglomerular feedback Extrinsic control (Sympathetic nerves)

Tubular Reabsorption & Secretion

By passive diffusion
Facillitated diffusion By primary active transport: Sodium

By secondary active transport: Sugars

and Amino Acids Hormonal control

Tubular Reabsorption
A transepithelial process whereby most

tubule contents are returned to the blood All organic nutrients are normally reabsorbed Water and ion reabsorption is hormonally controlled

Tubular Reabsorption

Tubular Secretion
Where substances move from peritubular capillaries

or tubule cells into filtrate Tubular secretion is important for: Disposing of substances not already in the filtrate Eliminating undesirable substances such as urea and uric acid Ridding the body of excess potassium ions Controlling blood pH

Tubular Secretion

Reabsorption & Secretion

proximal tubules(60-70%)

ion sodium Obligatory reabsorption iso-osmotic reabsorption facultative reabsorption

distal tubules

Peritubule capillaries
luminal & basolateral membranes

Transport Na+ sepanjang nefron

Transepithelial Glucose Transport

Osmolality of medullary Interstitium

4 X plasma (1200 1400 mOsm)
3 solutes involved:

Na+(Cl-) K+ urea

Purpose:

passive reabsorption of water (osmosis) in collecting ducts if ADH present

Osmolality of medullary Interstitium

Prox tub isoosmotic reabs
Descend A.H. water reabs w/o

solutes; filtrate becomes increasingly hypertonic Ascend A.H. solute reabs w/o water; filtrate becomes increasingly hypotonic Dist tub & coll d. water reabs (osmosis) if ADH present

Osmolality of medullary Interstitium

Filtrate at end of descend AH osm

adequate solutes for ascend AH to pump Filtrate at end of ascent AH osm (diluting segment) insures osmotic gradient between filtrate and interstitium

If diluting segment unable to form hypotonic fluid no osmotic gradient osmotic diuresis

Osmolality of medullary Interstitium

Countercurrent Multiplier System (ansa

Henle juxtamed nephron pars ascend)

thin passive thick Na+(Cl-)-K+-ATPase pump

Countercurrent Exchanger System (vasa

recta)

descend water exits; solutes enter ascend air enter; solutes exit

countercurrent multiplier & exchanger mechanisms in the juxtamedullary nephrons

Formation of Dilute Urine

Filtrate is diluted in the ascending loop of

Henle Dilute urine is created by allowing this filtrate to continue into the renal pelvis Collecting ducts remain impermeable to water; no further water reabsorption occurs This will happen as long as antidiuretic hormone (ADH) is not being secreted Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

Formation of Concentrated Urine

In the presence of ADH,

water permeable channels are added to the cell membranes of cells lining the DCT and collecting duct, and 99% of the water in filtrate is reabsorbed This equalizes the osmolality of the filtrate and the interstitial fluid ADH is the signal to produce concentrated urine The kidneys ability to respond depends upon the high medullary osmotic gradient

Osmolality of medullary Interstitium

ADH: neurohormone produced by NSO & PV (stored in posterior hypophysis) stimulus osmolarity of EF aquaporins on luminal membr of distal tubules & collecting ducts

ADH secretion

Effects of ADH

Osmolality of medullary Interstitium

Water reabs in collecting ducts:
passive through water channels ADH Need osmotic gradient between lumen (filtrate) and interstitium (EF) setup by countercurrent multiplier & maintained by countercurrent exchanger

CLEARANCE
Volume of plasma (ml) cleared of a substance in one minute
UX . V Cx = PX
If substance x is freely filtered, not reabsorbed, not secreted, then:

CX = Glomerular Filtration Rate example: INULIN

CX < CIN : substance filtered and reabsorbed CX > CIN : substance filtered and secreted CCREATININE Renal Function Index ( GFR) CPAH Renal Plasma Flow

Solute Clearance: Rate of removal from the Blood

Information on

Kidney Function GFR

Reabsorption rates Secretion rates

Reabsorption of substances by renal tubule

GLUCOSE
C = UV P Glucose < threshold completely reabsorbed Cgluc = 0 Glucose > threshold glucosuria (+ osmotic diuresis)

all filtered glucose will be reabsorbed, if < Tm

C = UV P

Glucose handling by nephron

Acid-base Homeostasis

ACID-BASE BALANCE
Kidneys excrete metabolic (fixed) acids:

HCO3- reabsorption H+ secretion (limiting pH 4.5 must be buffered in lumen)

HCO3 reabsorption in proximal tubules

New HCO3 reabsorption in proximal tubules

New HCO3 reabsorption in distal tubules & collecting ducts

Micturition
Wall of urinary bladder: Visceral smooth muscle plasticity Reflex: Stretch Reflex:

afferent center efferent effector Control: unconscious conscious cerebral cortex (inhibition) conditioned reflex
rec

Efferent: Parasympathetic bladder wall Somatic external sphincter (skeletal muscle)

Intravesical pressure (CYSTOMETROGRAM)

Ia = small press caused by 50 ml Ib = no press up to 400 ml (the urge to void first felt 150 ml) II = press caused by bladder contraction

II

Ib Ia

Urine storage in VU

Micturition