The Kidney Function

By M. Rasjad Indra Retty Ratnawati Endang Sriwahyuni Edwin Widodo

Clinical Case:
A 10 year boy has some symptoms: dark red urine and swollen/puffy face. This patient also complains about pain during swallowing, high fever and respiratory tract inflammation. Now, all symptomps are relieved. From physical analysis: increased blood pressure and edema on face and foot. From blood analysis: increased creatinin and urea and reduced plasma albumin. Also found proteinuria and gross hematuria.

Based on those anamneses and physical analysis, this patient is suspected to suffer glumerulonephritis, a disease of immune system with failure of glumerulus. This disease is self-relieved, with loss of signs and symptomps. Some patients can have worse outcome, the diseases becomes persistent and develop as permanent renal

failure. These signs and symptoms are the effect of glumerolus function failure leading to renal failure.
Human kidney plays important roles on maintaining volume and composition of extracelluler fluid. This organ maintains internal body environments. As a result, failure of structure and function of this organ will dysharmonize human body homeostasis.

Main function Excretion of metabolic waste products & foreign chemicals Regulation of:
water & electrolyte balances. body fluid osmolarity & electrolyte concentration. acid-base balance. arterial pressure.

Secretion, metabolism, and excretion of hormones Gluconeogenesis

Blood Clearance
Slide 6
Efective Pore What and how much should be removed Filtration Pressure Space Time Energy Efficient

Slide 11
Na K Cl Hydrogen Glucose Protein Creatinine Urea Still needed

Glomerulus

Unsufficient

Difusion Osmosis

Bioche mistry

Peritubular I

Tub. Proks.

Reabsorption

Secretion

Vasa recta

Ansa Henle

Slide 16
Peritubular II Excretion Tub. distalis

Slide 28

SELESAI

Renal Blood Flow (RBF)

1200 ml/minute or 20-25% of cardiac out put Both kidney weigh: 300 gr or 0.5% b.w. Blood flow per grams of kidney tissue: 4 ml / minute => 1200 ml / 300 gr, why? Blood flow is highest in the renal cortex, why? RBF & GFR change relatively little if arterial blood pressure between 80 - 180 mmHg, why?

The nephron ~ Functional Unit

Each kidney contains about 1 million nephrons The kidney cannot regenerate new nephrons.

After age 49 the number usually decrease 10 % every 10 years.

Regional differences in nephron structure:
Cortical nephrons: they have short loops. Juxtamedullary nephrons: they have long loops.

Urine formation results from: Glumerular filtration, tubular reabsorption, and tubular secretion.

Urinary excretion rate = Filtration rate- Reabsorption rate + Secretion rate

Ke Counter Current

Two capillary beds: The glomerular & Peritubular capillaries

Are arranged in series Separated by the efferent arterioles

Regulate the hydrostatic pressures in both sets of capillaries.

The glomerular (high ~ 60 mmHg) => for filtration. The peritubular (low ~ 13 mm Hg) => for reabsorption. The kidneys regulate the hydrostatic pressure of the glomerular & peritubular capilaries. Changing the rate of filtration and / or tubular reabsorption. Response to body homeostatic demands.
KEMBALI

Hydrostatic pressure:

By adjusting the resistances of afferent and efferent arterioles

Glomerular Filtration

Urine formation start with the filtration of plasma in the glomeruli: Glomerular Filtration Rate (GFR) determined by:
The balance of hydrostatic & colloid osmotic forces across the glomerular membrane The glomerular filtration coefficient (Kf) Net Filtr.Pressure= PG - PB - G+ B. GFR= Kf x Net Filtration Pressure

Glomerular filtration is rather non selective:

Protein are mostly retained in the plasma Low-molecular weight substance are freely filtered (excepts that are bound to the plasma protein). Negative charged large molecules are filtered less easily than positively charged molecules of equal molecules size

Macula densa

Juxtaglomerular cells

Autoregulation of Glomerular Filtration Rate (GFR) & Renal Blood Flow (RBF)

Sympathetic activation decrease RBF & GFR Hormonal & Autocoid:

Norepinephrine, epinephrine & Endothelin decreases

RBF & GFR

Angiotensin II : Constricts Efferent arteriol increases GFR Endothelial-derived Nitric Oxide (NO), Prostaglandin, & Bradykinin: increases RBF & GFR

Role of Tubuloglomerular Feedback:

Macula densa (Sodium Chloride level in Macula Densa) Renin-Angiotensin Efferent arteriolar resistance & Afferent arteriolar resistance

Myogenic Autoregulation High protein intake & High blood sugar => increase RBF & GFR

Arterial Pressure Glomerular hydrostatic pressure

GFR

Proximal Na Cl reabsorption

Macula Densa Na Cl

Renin
KEMBALI

Angiotensin II

Efferent Arteriolar resistance

Afferent Arteriolar resistance

Reabsorption & Secretion

Tubular reabsorption includes Passive & Active mechanism.

1.Across the tubular epithelial cells into interstitiel 2.Through the peritubular capillary membrane back into the blood

Active transport (against electrochemical gradient & requires energy.

1.Primary active transport

Expl: Sodium transport in luminal membrane prox. Tub. Expl.: Glucose & amino acid reabs.

2.Secondary active reabsorption

Secondary active Secretion:

Expl: Hydrogen ion: Counter-transport with sodium

reabsorption in luminal membrane

Glucose: All of the filtered are actively reabsorbed and sodium dependent. Urea & Chloride are passively reabsorb. Active absorb. of Na+ --> the driving force for tubular reabsorb. of water, glucose, amino acids, chloride and phosphate. Some organic compounds are secreted from the blood into the tubular urine.

Transport Maximum

Transport maximum for substances that are actively reabsorbed: Glucose 320 mg/min. Phosphate 0.10 mM/min. Sulfate 0.06 mM/min. Amino acid 1.5 mM/min. Uric acid 15 mg/min. Lactate 75 mg/min Plasma protein 30 mg/min Transport maximum for substances that are actively secreted: Creatinin 16 ng/min Para-aminohipuric acid 80 ng/min

Constituent Water Sodium Potasium Chloride Bicarbonate Phosphate Glucose Urea Uric acid Creatinine**

Filtered 167.5 liters 24,000 mmoles 720 mmoles 19,500 mmoles 4,500 mmoles 6g 150 g 50 g 8g 1.5 g

Reabsorbed 166 liters 23,900 mmoles 630 mmoles 19,400 mmoles 4,498 mmoles 5g 150 g 25 g 7.2 g 0g

Excreted 1.5 liters 100 mmoles 90 mmoles 100 mmoles 2 mmoles 1g 0g 25 g 0.8 g 1.8 g

Reabsorption of glucose

Glucose is cotransport with sodium across the luminal cell membrane (uphill)
the energy from:
the sodium gradient, how? the electrical gradient

Glucose leave the cell membrane to peritubular capillary blood by facilitated difussion

Glucose Threshold

The ability to reabsorb is limited At normal plasma glucose levels (65-90 mg/dl) => completely reabsorb. At 180-200 mg/dl => glucose first appear in the urine (threshold). Tubular transport maximum (Tm) for glucose: the maximal rate of glucose reabsorption.

Sodium (Na+): Most filtered sodium is reabsorbed. The proximal tubules: 70%. The loop of Henle: 20% The distal tub. and collecting duct: 9% The quantity of Na+ excreted =>important role in body sodium balance.

Countercurrent Mechanism

Loop of Henle (countercurrent multipliers) & Vasa recta (countercurrent ex-changers)

Loops of Henle: establish an osmotic gradient in the medulla.

The descending limb: water permeable The ascending limb: Active sodium transport Low water permeability

The vasa recta: remove water from the medulla.

Ke Slide 9

The collecting ducts:

Final regul. of Na+excretion.

Aldosterone and ADH: increase Na+ and water reabs. by the collecting duct. Potasium (K+): Filtered, reabsorb and secreted The cortical collecting tubules: important site of K+ secretion.

Ke Slide 5

The Clearance Concept (CX) to Quantify Kidney Function

Clearance(CX)= UX x V (ml plasma/ minute) U: urine, V: Volume of urine PX P: Plasma, x: substance The Inulin clearance (CIN) = GFR .....Why ? Endogenous Creatinine Clearance also = GFR ..... Why ? Clearance Ratio = Cx CInulin PAH : para-amino hipuric acid PAH clearance (CPAH)= Effective Renal Plasma Flow (ERPF) Renal Plasma Flow (RPF) = CPAH EPAH =PPAH-VPAH (Extraction Ratio) EPAH PPAH Renal Blood Flow (RBF) = RPF 1-Hematocrit Excretion Rate = Ux x V Reabsorption Rate = Filtered Load Excretion Rate = (GFR x Px) (Ux x V) Secretion Rate = Excretion Rate Filtered Load

Clearance Inulin ~ GFR (Glomerular Filtration rate)

Inulin: Not be reabsorbed or secreted by the kidney Not be metabolized, synthesized, or stored through the glomerular filtration Pass barrier unhindered Nontoxic Be able to measure in plasma and urine

Clearance PAH ~ ERPF (Effective Renal Plasma Flow)

Para-amino hipuric acid (PAH) is avidly secreted by tubules that it is almost completely cleared from all of the plasma in one passage of blood through the kidneys

mg ( x) / ml (urine) Xml (urine) / min ute Cx ml ( plasma ) / min ute mg ( x) / ml ( plasma )

Factor affecting urinary concentrating ability are:

Anti Diuretic Hormone The length of Henles loop. Tubule fluid and blood flow Urea.

Urea Recirculation in Renal Tubules

The two ureters are muscular tubes that carry the urine from the kidneys to the bladder. The urinary blader functions as a reservoir for urine and is periodically emptied (micturition).

MICTURITION A complex act involving autonomic and somatic nerves, spinal reflexes, and higher brain centers.

Ke slide 5

Increase [K+] plasma

Effect to adrenal cortex Secretion of aldosteron

Increase [K+] intracell (including kidney epithelial cell)

Kalium intake Normal kalium level Increase Plasma aldosteron

Increase natrium pump / kalium in tubulus distalis and ductus kolektivus

Increase Kalium secretion Increase Kalium excretion

Kembali ke 26

Angiotensinogen

Liver

Kidney

Renin

Angiotensin I Reduce Effective Blood volume Paru Converting enzyme

Angiotensin II

Pembuluh darah

Korteks Adrenal

Hipotalamus

Vasokonstriksi

Sekresi Aldosteron

Sekresi ADH

Pusat Haus

Blood pressure >

Reabsorbsi Natrium

Reabsorbsi H2O

Minum

Volume darah arterial efektif normal

Kembali ke 15

Based on this data : Konsentrasi inulin plasma Konsentrasi inulin urine Konsentrasi glukosa plasma Konsentrasi glukosa urine Konsentrasi PAH plasma Konsentrasi PAH urine Aliran urine rata-rata Hematokrit darah

= 0,3 = 6,0 = 4,0 = 20,0 = 0,02 = 2,4 = 5 = 45

mg / ml mg / ml mg / ml mg / ml mg / ml mg / ml ml / minute %

Answer these following questions : Glomerular Filtration Rate (GFR) = ...........ml / minute Clearance PAH = ml plasma / minute Clearance glucose = ml plasma / minute Glucose reabsorbsi rate = ...........mg / minute Renal blood flow (RBF) = ..............l / minute