Departement of Physiology

School of Medicine
University of Sumatea Utara

*Describe the morphology of a typical nephron and its blood supply.

*Define autoregulation and list the major theories advanced to explain
autoregulation in the kidneys.
*Define glomerular filtration rate, describe how it can be measured,
and list the major factors affecting it.
*Outline tubular handling of Na+ and water.
*Discuss tubular reabsorption and secretion of glucose and K+ .
*Describe how the countercurrent mechanism in the kidney operates
to produce hypertonic or hypotonic urine.
*List the major classes of diuretics; understand how each operates to
increase urine flow.
*Describe the voiding reflex and draw a cystometrogram

* Excretion of metabolic waste products and foreign

chemicals

* Regulation of water and electrolyte balances

* Regulation of body fluid osmolality and electrolyte
concentrations

* Regulation of arterial pressure

* Regulation of acid-base balance
* Secretion, metabolism, and excretion of hormones
* Gluconeogenesis

The kidneys are the primary means for eliminating

waste products of metabolism :
*Urea (from the metabolism of amino acids),
*Creatinine (from muscle creatine),
*Uric acid (from nucleic acids),
*End products of hemoglobin breakdown (such as
bilirubin), and metabolites of various hormones.
*Toxins and other foreign substances that are either
produced by the body or ingested, such as pesticides,
drugs, and food additives.

* This is also true for

water and for most

other electrolytes, such
as chloride, potassium,
calcium, hydrogen,
magnesium, and
phosphate ions

* Long-term regulation of arterial pressure by

excreting variable amounts of sodium and
water.

* Short-term arterial pressure regulation by

secreting vasoactive factors or substances,

such as renin, that lead to the formation of
vasoactive products (e.g., angiotensin II).

* The kidneys are the only means of eliminating

from the body certain types of acids, such as

sulfuric acid and phosphoric acid, generated by
the metabolism of proteins.

* Along with the lungs and body fluid buffers.

* Secrete erythropoietin, which stimulates the

production of red blood cells.

* One important stimulus for erythropoietin

secretion by the kidneys is hypoxia

* activate vitamin D (25-hydroxycalciferol) to

1,25-dihydroxyvitamin D3 (calcitriol).

* synthesize glucose from amino acids and other

precursors during prolonged fasting.

* Functional unit of kidney.

* The size of the kidneys between species varies,
as does the number of nephrons they contain.

* Each human kidney has approximately 1,0 1,2

million nephrons.

* Cortical and Juxtamedullary nephron.

Vascular supply to the nephron

Proximal convoluted
tubule
Glomerulus
Arcuate vein

Efferent arteriole
Afferent arteriole
Distal convoluted tubule

Arcuate artery
Collecting duct
Vasa recta
Thick ascending limb
of the loop of Henl
Descending limb
loop of Henl

Thin ascending limb

of the loop of Henl

Cortical Nephron
* Glomerulus terletak 2/3
bagian luar cortex
* 85% dari seluruh nephron
* Loop of henle pendek

* Dikelilingi oleh kapiler

peritubular berbentuk
jala network

Juxtamedullary Nephron
* Terletak bagian dalam
cortex dekat medulla
* 15% dari seluruh nephron
* Loop of henle panjang,
lebih dalam masuk ke
medulla
* Dikelilingi kapiler
berbentuk U vasa
recta

Structure of the Bowmans (glomerular) capsule

Parietal layer of
glomerular capsule

Afferent arteriole
Juxtaglomerular
cell

Capsule
space
Efferent arteriole
Proximal
convoluted
tubule
Endothelium
of glomerulus

Podocyte
Pedicel

* Stellate cells called mesangial cells are located

between the basal lamina and the endothelium.

They are similar to cells called pericytes, which are
found in the walls of capillaries elsewhere in the
body.

* Mesangial cells are especially common between two

neighboring capillaries, and in these locations the
basal membrane forms a sheath shared by both
capillaries (Figure 382).

* The mesangial cells are contractile and

play a role in the regulation of
glomerular filtration.

* Mesangial cells secrete the extracellular

matrix, take up immune complexes, and

are involved in the progression of
glomerular disease.

Involves three main processes:

* 1.Filtration
* 2.Reabsorption
* 3.Secretion

Is composed of three layers:

1. fenestrated glomerular endothelium
2.basement membrane
3.filtration slits are formed by the pedicels of
the podocytes
Substance are filtered are on the basis of size
and/or electrical properties

Insert fig. 17.8

* Endothelial capillary pores are large fenestrae.

* 100-400 times more permeable to plasma, H20,
and dissolved solutes than capillaries of
skeletal muscles.
* Pores are small enough to prevent RBCs,
platelets, and WBCs from passing through the
pores.

*Filtrate must pass through the basement

membrane:

* Thin glycoprotein layer.

* Negatively charged.

*Podocytes:

* Foot pedicels form small filtration slits.

* Passageway through which filtered molecules must pass.

The filtration barrier - podocytes

basal
lamina

pedicel

filtration
slit

fenestrated
endothelium

basal
lamina
podocyte
filtration
slit
fenestrated
endothelium

secondary
process
(pedicel)

podocyte
primary cell body
process

The filtration barrier - pedicels

Bowmans
space
pedicel

filtration
slit

capillary

Common component of the glomerular filtrate:

* Organic molecules: glucose,amino acids

* Nitrogenous waste: urea, uric acid, creatinine
* Ions: sodium, potassium, chloride

* Rumus tekanan filtrasi

* Kf, the glomerular ultrafiltration coefficient, is the

product of the glomerular capillary wall hydraulic

conductivity (ie, its permeability) and the effective
filtration surface area.

* PGC is the mean hydrostatic pressure in the glomerular

capillaries, PT the mean hydrostatic pressure in the

tubule (Bowmans space), GC the oncotic pressure of the
plasma in the glomerular capillaries, and T the oncotic
pressure of the filtrate in the tubule (Bowmans space).

* Glomerular hydrostatic pressure (blood pressure) promotes

filtration=55 mmHg

* Capsular hydrostatic pressure opposes filtration=15 mmHg

* Glomerular osmotic pressure opposes filtration=30 mmHg
* Net filtration pressure = 55 (15+30) =10 mmHg

GAYA FISIK YANG TERLIBAT DALAM FILTRASI

GLOMERULUS
1. Tekanan darah kapiler
gomerulus (PGC) = 55 mmHg
2. Tekanan osmotik koloid
plasma (IIGS) = 30 mmHg
3. Tekanan hidrostatik kapsul
Bowman (PBC) = 15 mmHg
Tekanan filtrasi netto :
= PGC (IIGS PBC)
= 55 - (30+15)
= 10 mmHg

PI

PC

Aff.Art.

Eff.Art.
PGC

GS
PBC

The total amount of filtrate formed by the

kidney per minutes

*Sekitar 20% dari renal plasma flow

*Nilai GFR ditentukan oleh:

* (1) keseimbangan antara tekanan hidrostatis dan

osmotik
* (2) filtration coefficient kapiler (Kf) yaitu
permeabilitas dan area permukaan filtrasi

*GFR normal 125 ml/min, atau 180 L/day.

To counteract changes in GFR

Myogenic mechanism

* Increased systemic pressure: Autoregulation: afferent arteriole

diameter decreased (constricted) to maintain the GFR

* Decreased systemic pressure: Autoregulation: afferent arteriole

diameter increased (dilated) to maintain the GFR

* Inulin: (Polysaccharide from Dahalia plant)

* Freely filterable at glomerulus
* Does not bind to plasma proteins
* Biologically inert
* Non-toxic, neither synthesized nor metabolized in kidney
* Neither absorbed nor secreted
* Does not alter renal function
* Can be accurately quantified
* Low concentrations are enough (10-20 mg/100 ml plasma)

*Creatinine:

* End product of muscle creatine metabolism

* Used in clinical setting to measure GFR but less
accurate than inulin method
* Small amount secrete from the tubule

*Para-aminohippurate (PAH):

* An organic anion not present in body

* Freely filtered, secreted but not reabsorbed by

nephron
* Non-toxic, neither synthesized nor metabolized in
kidney

* Low concentrations are enough (10 mg/100 ml plasma)

*RPF = ClearancePAH = UPAH.V / PPAH

Solute Clearance:
Rate of removal from the Blood

Figure 19-16: Inulin clearance

Concept of clearance
Qx extracted = Qx excreted
Px . Cx = Ux . V

GFR = Cx =

Where,
Cx = Clearance of substance X (mg/min)
Ux = Urine concentration of X (mg/ml)
Px = Plasma concentration of X (mg/ml)
V = Urine flow rate of X (ml/min)

Ux . V
Px

Effective renal plasma flow =GFR

Effective renal blood flow =

Renal blood flow =

Extraction ratio (0.9) =

ERBF = Cx =

RBF =

ERPF
1 - Hct

Hct=hematocrit

ERBF
Extraction ratio

APAH - VPAH
APAH

APAH = arterial plasma PAH

VPAH = vein plasma PAH

* Micturition is the process by which the urinary bladder

empties when it becomes filled. This involves two main

steps:

* First, the bladder fills progressively until the tension in its

walls rises above a threshold level; this elicits the second
step,

* second step, which is a nervous reflex called the micturition

reflex that empties the bladder or, if this fails, at least causes
a conscious desire to urinate.

* Although the micturition reflex is an autonomic spinal

cord reflex, it can also be inhibited or facilitated by
centers in the cerebral cortex or brain