The Kidney Function

By
M. Rasjad Indra

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

Secretion, metabolism, and excretion of

hormones
Gluconeogenesis

Blood Clearance
EFFECTIVE

EFFICIENT

WHAT
HOW MUCH

PORE

PRESSURE

PACE
TIME
ENERGY

FILTRATION

Glomerulus

Na
K
Cl
Hydrogen
Glucose
Protein
Creatinine
Urea

STILL NEEDED

MORE TO BE
EXCRETED

Diffusion
Osmosis

Biochemistry

REABSORPTION

SECRETION

Peritubular I

Prox Tub..

Vasa recta

Loop Henle

Peritubular II

Distalis Tub.

EXCRETION
SELESAI

Renal Blod Flow

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.

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 arterioles

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

Glomerular Filtration
Urine formation start with the filtration of plasma in the
glomeruli:
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

Role of Tubulo-glomerular Feedback

Arterial Pressure
Glomerular hydrostatic
pressure
GFR
Macula Densa
[Na Cl]

Proximal Na Cl
reabsorption

Renin

Angiotensin II

Efferent Arteriolar
resistance

KEMBALI

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.

2.Secondary active reabsorption

Expl.: 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 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 (6590 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 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

The Clearance Concept (CX) to Quantify Kidney Function

Clearance(CX)= UX x V (ml plasma/ minute)

PX

The Inulin clearance (CIN) = GFR .....Why ?

Endogenous Creatinine Clearance also = GFR ..... Why ?

Clearance Ratio = Cx
CInulin

Effective Renal Plasma Flow (ERPF) = CPAH

Renal Plasma Flow (RPF) = CPAH

EPAH

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

Inulin:

Not be reabsorbed or secreted by the kidney

Not be metabolized, synthesized, or stored
Pass through the glomerular filtration barrier
unhindered

Nontoxic PAH ~ ERPF

Clearamce

Be able to measure in plasma and urine

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 )

Urinary tract consists of:

1. Pair of ureter
2. Vesica urinaria
3. Urethra

URETER:
* Muscular tubes
that extend
inferiorly from
the kidney.
* Begins as a
continuation of
pelvis renalis
through the hilus

Vesica Urinaria:
A hollow muscular
organ
Functions as
temporarily
storage reservoir
for urine

Urethra:

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

Body fluid
60% (45-75)
water

Intracellular
40 %

Extracellular
20 %

(42 liter in 70 kg

(14 liter in 70 kg

young adult)

young adult)

Interstitial
15 %
(10.5 liter in 70 kg
young adult)

Plasma
5%

Transcellular
1-3 %

(3.5 liter in 70 kg

(Cerebrospinal)

young adult)

(Aqueous humor)

Electrolyte Composition of Body Fluid

Electrolytes
Cation:
Na+
K+
Ca2+
Mg2+
Total
Anion:
ClHCO3Protein
Others
Total

Plasma
(mEq/L)

142
4
5
2
153
103
25
17
8
153

Interstitial Fluid
(mEq/Kg H2O)

145
4
3
2
154
117
28
9
154

Intracellular
Fluid (mEq/Kg
H2O)
10
159
1
40
210
3
7
45
155
210

Daily Intake and Output of Water (in

ml/day)
Normal
Intake
Fluid ingested
From metabolism
Total intake
Output
Insensible-Skin
Insensible-Lungs
Sweat
Feces
Urine
Total output

Prolonged
Heavy Exercise

2100
200
2300

?
200
?

350
350
100
100
1400
2300

350
650
5000
100
500
6600

Definition of Edema:

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

Starling Hypothesis
The balance of hydrostatic and oncotic pressures across the capillary endothelium

Mean capillary hydrostatic pressure (Pc): 25 mmHg

Interstitial fluid hydrostatic pressure (P

IF

): 0 mmHg

Capillary oncotic pressure (c): 28 mmHg

Interstitial fluid oncotic pressure ( ): 3 mmHg
IF

Arterial end of capillary:

Venous end of capillary:

Pc= 40 mmHg; P = 0 mmHg

IF
c= 28 mmHg; = 3 mmHg
IF
Net Filtration= 35-0-28+3= 10

Pc= 10 mmHg; P = 0 mmHg

IF
c= 28 mmHg; = 3 mmHg
IF
Net Absorption= 15-0-28+3= -10

Causes of Extracellular Edema

1. Increased capillary pressure
Excessive kidney retention
High venous pressure
Decreased arteriole resistance

2. Decreased plasma proteins

Loss of protein in urine
Loss of protein from denuded skin
Failure of produce protein

 3. Increased capillary permiability

Immune reaction
Toxin
Bacteria infection
Vitamin deficiency (exp. Vit C)

4. Blockage of lymph return

Cancer
Paracyte infection (Filaria)
Surgery
Congenital absence or abnormal of
Lymphatic vessels

Acid-Base Balance

What is Acid and Base ?

Acid is proton (H+) donor
Base is proton (H+) acceptor
The most important acid in the blood is H2CO3
The most important base is HCO3 H2CO3 <=> HCO3-+H+

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

HCO logH logK log HCO

logH logK log
S.pCO

H2CO3

HCO
pH pK log

S.pCO2

pH pK log

HCO

0,03xS.PCO
2

Henderson-Hasselbalch Equation
pH=pK + log kidneys
lungs
pH=pK + log [HCO3-]
PCO2

pH=6,1 + log [HCO3-]

0.03 * P CO2

1.

6 ,1 log

pH

[ HCO
PCO

2.

[ H

]( nmol

[ HCO 3] 20

[ H 2CO 3] 1

3]
2

/ L ) 24 x

PCO

2 ( mmHg

HCO

pH= 7.70 [H+] = 20 nmol/L

3 mEq

)
/ 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

160

ACID:
Result of metabolism and digestion
Consist of: volatile and nonvolatile
Volatile
HCl, H2SO4, HNO3, H3PO4, NH4+, H2CO3
H2CO3 (primary)<=>H20 + CO2
Eliminated as CO2 gas via lungs.

Nonvolatile:
Small amount.
Lactic acid, acetic acid
Removed via the kidney

Base :

NaOH: Sodium hydroxide

KOH: Potasium hydroxide
NH +: Ammonia
3
HCO -: Bicarbonate
3

Amphoteric 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 stability

1. Acid

<=> Conjugate base : H PO - <=>

2 4
HPO 2- + H+
4

H CO <=> HCO - + H+
2 3
3
2. Protein :
NH + <=> NH + H+
4
3
Albumin; Globulin
Hemoglobin
3. Lung and Kidney

[H2CO3 ]~PaCO2= Respiratory component

[H2CO3]<=>PaCO2 x (0.03)
PaCO2 :
Provides a measure of H2CO3
The respiratory component.

Normal:
PaCO2 = 40 mm Hg.
H2CO3 = 40 x 0.03 = 1.2 mEq/L

HCO3-=Metabolic component
Regulated by the kidney.
By modulating the rate of re-absorption

Metabolic acid-base imbalance:

Kidney-related
Non-kidney-related
Electrolite Disturbance
(Chloride depletion)

The acidity of blood

Depend on [H+]
Expressed by pH
The [H+] increase -> the pH decrease
pH = -log[H+]
pH = pK + log [HCO3- / H2CO3]
Henderson Hasselbalch equation

Arterial Blood Gas (ABG):

pH = measured
- HCO3- = calculated
PaCO2 = measured

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

Acid-Base Disturbance
Simple :
Respiratory acidosis: PaCO2 high / HCO3normal or slightly high
Respiratory alkalosis: PaCO2 low /HCO3normal or low
Metabolic acidosis: HCO3- low / PaCO2 normal
or low
Metabolic alkalosis: HCO3- high / PaCO2
normal or high

Mixed / Combination:
(Respiratory + Metabolic)

Physiologic compensation
Primary disorder
Respiratory acidosis

Physiol. compensation
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)

Exercise
pH = 7.33
PaCO2 = 50 mmHg
HCO3- =25.8 mEq/L
Answer:
Acidemia
Primary respiratory
Acute

pH = 7.55
PaCO2 = 30 mmHg
HCO3- = 23.4 mEq/L
Answer:
Alkalemia
Primary respiratory
Acute

Exercise
pH = 7.31
PaCO2 = 29.5 mmHg
HCO3- = 14.5 mEq/L
Answer:
Acidemia
Primary metabolic
Respiratory
compensation

pH = 7.59
PaCO2 = 46.5 mmHg
HCO3- = 45 mEq/L
Answer:
Alkalemia
Primary metabolic
Respiratory
compensation