GLOMERULAR FUNCTION

Internal structure of the kidney

Blood supply of the kidney: 21% of the cardiac output = 1200 ml/mnt

Vascular supply to the nephron

Proximal convoluted tubule Glomerulus Arcuate vein 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

Efferent arteriole Afferent arteriole Distal convoluted tubule

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 Pedicel

Podocyte

 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.

Formation of Urine
Involves three main processes: 1.Filtration 2.Reabsorption 3.Secretion

Filtration membrane
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

Glomerular Filtration Membrane

Insert fig. 17.8

Glomerular Filtration Membrane

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.

Glomerular Filtration Membrane

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

pedicel basal lamina

filtration slit

fenestrated endothelium

basal lamina podocyte

filtration slit
fenestrated endothelium podocyte primary cell body process

secondary process (pedicel)

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).

Forces affecting filtration

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

Glomerular filtration rate

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.

Autoregulation Mechanism
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

Qualities of agents to measure 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 Ux . V GFR = Cx = Px 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)

Effective renal plasma flow =GFR Effective renal blood flow =

ERBF = Cx =

ERPF 1 - Hct

Hct=hematocrit

Renal blood flow =

RBF =

ERBF Extraction ratio

APAH = arterial plasma PAH VPAH = vein plasma PAH

Extraction ratio (0.9) =

APAH - VPAH APAH

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