The Kidney FunctionByM. Rasjad Indra

Main functionExcretion of metabolic waste products & foreign chemicalsRegulation of:water & electrolyte balances.body fluid volume & osmolarity acid-base balance.arterial pressure.Secretion, metabolism, and excretion of hormonesGluconeogenesis

Blood ClearanceEFFECTIVEEFFICIENTWHATHOW MUCHPACE TIMEENERGYFILTRATIONSTILL NEEDEDMORE TO BE EXCRETEDREABSORPTIONSECRETIONPOREPRESSURENaKClHydrogenGlucoseProteinCreatinineUreaGlomerulusProx Tub..Loop HenleDistalis Tub. Peritubular IVasa rectaPeritubular IIDiffusionOsmosisBio-chemistryEXCRETIONSELESAI

Renal Blod Flow1200 ml/minute or 20-25% of cardiac out putBoth 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 UnitEach kidney contains about 1 million nephronsThe 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 capillariesAre arranged in seriesSeparated by the efferent arteriolesRegulate the hydrostatic pressures in both sets of capillaries.Hydrostatic pressure:The glomerular (high ~ 60 mmHg) => for filtration.The peritubular (low ~ 13 mm Hg) => for reabsorption.By adjusting the resistances of afferent and efferent arteriolesThe 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

Glomerular FiltrationUrine formation start with the filtration of plasma in the glomeruli:GFR determined by:The balance of hydrostatic & colloid osmotic forces across the glomerular membraneThe glomerular filtration coefficient (Kf)Net Filtr.Pressure= PG - PB - G+ B.GFR= Kf x Net Filtration PressureGlomerular filtration is rather non selective:Protein are mostly retained in the plasmaLow-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 densaJuxtaglomerular cells

Role of Tubulo-glomerular Feedback

Reabsorption & SecretionTubular reabsorption includes Passive & Active mechanism.Across the tubular epithelial cells into interstitielThrough the peritubular capillary membrane back into the blood Active transport (against electrochemical gradient & requires energy.Primary active transportExpl: Sodium transport in luminal membrane prox. Tub.Secondary active reabsorptionExpl.: Glucose & amino acid reabs. 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 MaximumTransport maximum for substances that are actively reabsorbed:Glucose320 mg/min.Phosphate0.10 mM/min.Sulfate0.06 mM/min.Amino acid1.5 mM/min.Uric acid15 mg/min.Lactate75 mg/minPlasma protein30 mg/minTransport maximum for substances that are actively secreted:Creatinin16 ng/minPara-aminohipuric acid80 ng/min

Constituent

Filtered

Reabsorbed

Excreted

Water

167.5 liters

166 liters

1.5 liters

Sodium

24,000 mmoles

23,900 mmoles

100 mmoles

Potasium

720 mmoles

630 mmoles

90 mmoles

Chloride

19,500 mmoles

19,400 mmoles

100 mmoles

Bicarbonate

4,500 mmoles

4,498 mmoles

2 mmoles

Phosphate

6 g

5 g

1 g

Glucose

150 g

150 g

0 g

Urea

50 g

25 g

25 g

Uric acid

8 g

7.2 g

0.8 g

Creatinine**

1.5 g

0 g

1.8 g

Reabsorption of glucoseGlucose is cotransport with sodium across the luminal cell membrane (uphill)the energy from:the sodium gradient, how?the electrical gradientGlucose leave the cell membrane to peritubular capillary blood by facilitated difussion

Glucose ThresholdThe ability to reabsorb is limitedAt 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 MechanismLoop of Henle (countercurrent multipliers) & Vasa recta (countercurrent ex-changers) Loops of Henle: establish an osmotic gradient in the medulla.The descending limb:water permeableThe ascending limb:Active sodium transportLow water permeabilityThe vasa recta: remove water from the medulla.Ke Slide 8

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 4

Clearance(CX)= UX x V (ml plasma/ minute) PXThe Inulin clearance (CIN) = GFR .....Why ?Endogenous Creatinine Clearance also = GFR ..... Why ?Clearance Ratio = Cx CInulinEffective Renal Plasma Flow (ERPF) = CPAHRenal Plasma Flow (RPF) = CPAH EPAHRenal Blood Flow (RBF) = RPF 1-HematocritExcretion Rate = Ux x VReabsorption Rate = Filtered Load Excretion Rate = (GFR x Px) (Ux x V)Secretion Rate = Excretion Rate Filtered LoadThe Clearance Concept (CX) to Quantify Kidney Function

Inulin:Not be reabsorbed or secreted by the kidneyNot be metabolized, synthesized, or storedPass through the glomerular filtration barrier unhinderedNontoxicBe able to measure in plasma and urineClearance Inulin ~ GFRPAH is avidly secreted by tubules that it is almost completely cleared from all of the plasma in one passage of blood through the kidneysClearamce PAH ~ ERPF

Urinary tract consists of:1. Pair of ureter2. Vesica urinaria3. UrethraURETER:* Muscular tubes that extend inferiorly from the kidney.* Begins as a continuation of pelvis renalis through the hilus

Vesica Urinaria:A hollow muscular organFunctions as temporarily storage reservoir for urineUrethra:Extends from collum vesicae to the exterior.Differ in length and function between female and male

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

Ke slide 4

Fluid and Electrolyte Balance

Body Fluid Compartment

Body Fluid Volume

Electrolyte Composition of Body Fluid

Electrolytes

Plasma

(mEq/L)

Interstitial Fluid (mEq/Kg H2O)

Intracellular Fluid (mEq/Kg H2O)

Cation:

Na+

142

145

10

K+

4

4

159

Ca2+

5

3

1

Mg2+

2

2

40

Total

153

154

210

Anion:

Cl-

103

117

3

HCO3-

25

28

7

Protein

17

-

45

Others

8

9

155

Total

153

154

210

Daily Intake and Output of Water (in ml/day)

Normal

Prolonged

Heavy Exercise

Intake

Fluid ingested

2100

?

From metabolism

200

200

Total intake

2300

?

Output

Insensible-Skin

350

350

Insensible-Lungs

350

650

Sweat

100

5000

Feces

100

100

Urine

1400

500

Total output

2300

6600

Definition of Edema:An increase in the interstitial compartement of extracellular fluid volume (Harrisons).

Starling HypothesisThe balance of hydrostatic and oncotic pressures across the capillary endothelium

Mean capillary hydrostatic pressure (Pc): 25 mmHgInterstitial fluid hydrostatic pressure (PIF): 0 mmHgCapillary oncotic pressure (c): 28 mmHgInterstitial fluid oncotic pressure (IF): 3 mmHg

Arterial end of capillary:Pc= 40 mmHg; PIF= 0 mmHgc= 28 mmHg; IF= 3 mmHgNet Filtration= 35-0-28+3= 10

Venous end of capillary:Pc= 10 mmHg; PIF= 0 mmHgc= 28 mmHg; IF= 3 mmHgNet Absorption= 15-0-28+3= -10

Causes of Extracellular Edema1. Increased capillary pressureExcessive kidney retentionHigh venous pressureDecreased arteriole resistance2. Decreased plasma proteinsLoss of protein in urineLoss of protein from denuded skinFailure of produce protein

3. Increased capillary permiabilityImmune reactionToxinBacteria infectionVitamin deficiency (exp. Vit C)4. Blockage of lymph returnCancerParacyte infection (Filaria)SurgeryCongenital absence or abnormal of Lymphatic vessels

Acid-Base Balance

What is Acid and Base ?Acid is proton (H+) donorBase is proton (H+) acceptorThe most important acid in the blood is H2CO3The most important base is HCO3-H2CO3 HCO3-+H+

pH:Symbol of H+ ion levelspH = -log [H+]

Henderson-Hasselbalch EquationpH=pK + log kidneys lungs

pH=pK + log [HCO3-] PCO2

pH=6,1 + log [HCO3-] 0.03 * P CO2

pH= 7.70 [H+] = 20 nmol/L pH=7.20 [H+]=60 nmol/L 7.60 25 7.10 80 7.50 30 7.00 100 7.40 40 6.90 125 7.30 50 6.80 1601.2.

ACID:Result of metabolism and digestionConsist of: volatile and nonvolatileVolatileHCl, H2SO4, HNO3, H3PO4, NH4+, H2CO3H2CO3 (primary)H20 + CO2 Eliminated as CO2 gas via lungs.Nonvolatile:Small amount.Lactic acid, acetic acid Removed via the kidney

Base :NaOH: Sodium hydroxideKOH: Potasium hydroxideNH3+: AmmoniaHCO3-: BicarbonateAmphoteric Substance: Can function as both an acid and a base. Glycine( +H3N-CH2-COO-): NaOH++H3N-CH2-COO-=>H2N-CH2-COO-Na+ + H2O HCl + +H3N-CH2-COO- => Cl-+H3N-CH2-COOH

Buffer: Minimize the change & promote stability1. Acid Conjugate base : H2PO4- HPO42- + H+H2CO3 HCO3- + H+NH4+ NH3 + H+2. Protein :Albumin; GlobulinHemoglobin 3. Lung and Kidney

[H2CO3 ]~PaCO2= Respiratory component[H2CO3]PaCO2 x (0.03)PaCO2 :Provides a measure of H2CO3The respiratory component.Normal:PaCO2 = 40 mm Hg.H2CO3 = 40 x 0.03 = 1.2 mEq/L

HCO3-=Metabolic componentRegulated by the kidney.By modulating the rate of re-absorptionMetabolic acid-base imbalance:Kidney-relatedNon-kidney-relatedElectrolite Disturbance(Chloride depletion)

The acidity of bloodDepend on [H+]Expressed by pHThe [H+] increase -> the pH decreasepH = -log[H+]pH = pK + log [HCO3- / H2CO3]Henderson Hasselbalch equationArterial Blood Gas (ABG):pH = measured- HCO3- = calculatedPaCO2 = measured

Normal Range:PaCO2 = 38 to 42 mmHgHCO3- = 22 to 26 mEq/LpH = 7.38 to 7.42HCO3- / H2CO3 = 20 : 1Acid-base disturbance (blood):Acidemia: pH< 7.38Alkalemia: pH> 7.42

Acid-Base DisturbanceSimple :Respiratory acidosis: PaCO2 high / HCO3- normal or slightly highRespiratory alkalosis: PaCO2 low /HCO3- normal or lowMetabolic acidosis: HCO3- low / PaCO2 normal or lowMetabolic alkalosis: HCO3- high / PaCO2 normal or highMixed / Combination: (Respiratory + Metabolic)

Physiologic compensation

Primary disorder

Physiol. compensation

Respiratory acidosis

Kidney retention of HCO3-; excretion of H+

Respiratory alkalosis

Kidney excretion of HCO3-; retention of H+

Metabolic acidosis

Lung excretion of H+ (CO2).

Metabolic alkalosis

Lung possible retention of H+ (CO2)

ExercisepH = 7.33PaCO2 = 50 mmHgHCO3- =25.8 mEq/LAnswer:AcidemiaPrimary respiratory AcutepH = 7.55PaCO2 = 30 mmHgHCO3- = 23.4 mEq/LAnswer:AlkalemiaPrimary respiratoryAcute

ExercisepH = 7.31PaCO2 = 29.5 mmHgHCO3- = 14.5 mEq/LAnswer:AcidemiaPrimary metabolicRespiratory compensation

pH = 7.59PaCO2 = 46.5 mmHgHCO3- = 45 mEq/LAnswer:AlkalemiaPrimary metabolicRespiratory compensation