Renal blood flow(RBF)&glomerular filtration rate(GFR).

Dr.M.A.M.Shaikhani.

The nephron: Is the functional unit of the kidneys. Consists of:Glomerulus,afferent(AA),efferent arterioles(EA),bowmans

capsule(BC),proximal tubule(PT),loop of hole(LH),distal tubule(DT) & collecting tubule(CT) which ends into the collecting duct(CD).

CD collects urine from 4000 nephrones & each kidney contains 500 collecting ducts ,so each kidney contains 2000000 nephron.

The venous system draining & surrounding the juxta(near) medullary tubules form a special peritubular network in the medulla of the kidneys called vasa recta.

The nephrones are of 2 types:1.Cortical:about 4/5 to 2/3 of the total kidney nephrones.2.Guxta medullary: about 1/5 to 1/3 of kidney nephrones.

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Major functions of the kidneys:• Excretion of metabolic waste products &foreign chemicals

• Regulation of water &electrolyte balances

• Regulation of body fluid osmolality & electrolyte concentrations

• Regulation of arterial pressure

• Regulation of acid-base balance

• Secretion, metabolism & excretion of hormones as erythropoietin.

• Gluconeogenesis.

• Activation of Vitamin D.

These functions are accomplished by:1.Glomerular filtration & tubular reabsorption: as 1/5 of plasma is

filtered through the glomeruli , 99% of this filtrate is reabsorbed back into the blood by the tubules & only 1% pass to urine.

2.Secretion of some substances by the tubules into the tubular lumen.Urinary excretion rate = filtration rate - reabsorption rate + secretion

rate.3.Bicarbonate regeneration by the tubules& its reabsorption back into

blood by the tubules to control the acid base balance of the blood.The RBF = 1200ml./min. cardiac output = 5600 ml./min. So RBF is 1200/5600 >< 100 = 21% of cardiac output. Range of 12% to

30%.

RBF & Pressures:1. There is high pressure in the small renal arterioles ,afferent arterioles &

glomerulus (100 to 80 mm.Hg.) to assist filtration of plasma at the glomerulus into the BC.

2.There is low pressures in the EA, peritubular capillaries, venioles& vasa recta(13,10,8,6mm.Hg.) to assist reabsorption of the fluid from the interstitium & tubules into them.

3.The peritubular capillaries & vasa recta absorb 4 times as much as fluid as any other capillary system in the body(180 liter filtered daily through the glomerulus only 1.5 liter becomes urine, due to:

1.    1. The low pressure .2.     2.High porosity .3     3.The slow flow of blood through these capillaries as only 1 to 2% of RBF

pass through vasa recta.

Characteristics of glomerular membrane:1.Consists of 3 layers:A . Capillary endothelium with fenestra which allow passage of only small molecules.B. Basement membrane composed of negative charged proteoglycan which impedes

the passage of important negative charged plasma proteins from blood through the glomerular membrane into the urine by charge repulsion.

C. BC epithelial cells containing foot processes which oppose each other to form slit pores which allow only passage of small molecules only.

These 3 important characters of glomerular membrane prevent passage of high molecular weight(MW) proteins as albumen & allows only low MW small proteins.

Glomerular permeability(GP) = concentration at filtered side/concen. At plasma sideFor example GP of Inulin (MW of 5200) is 1. GP of very small proteins(MW of 30000) is 0.5 .While GP of albumin(MW of 69000) is 0.005 i.e only small amounts of large MW

proteins are filtered through the glomerulus.

The size of slit pores determine the passage of molecules as the pores diameter is about 80 angstromes.

The characters of glomerular membrane augment each other as although the albumin diameter is 60 angstromes but their repulsion by negative charged basement membrane proteins as they are also negatively charged prevent their passage through the glomerulus, so both characters augment each other.

So the glomerular filtrate is the same as plasma with the exception that it contains no significant amount of plasma proteins, the concentration of non protein negative charged ions as Cl & HCO3 is 5% Lower than in plasma & concentration of non protein positive ions as Na+ is 5% higher than in the plasma.

GFR:Is The glomerular filtrate formed each minute in all nephrones of

both kidneys. It is 180 liter/day or 125ml./min.The glomerular filtration depends on the filtration pressure of

10mm. Hg. = glomerular pressure (60mm.Hg.) + BC oncotic pressure (zero) - Capillary oncotic pressure (32 mm.Hg.) - BC hydrostatic pressure (18 mm.Hg.).

GFR=125ml/min = Filtration pressure >< filtratrion coefficient (KF).

constant(KF) = GFR in both kidneys /filtration pressure = 125/10= 12.5 ml /min /mm.Hg.

Factors affecting GFR: 1.RBF. 2.AA dilatation. 3. EA constriction. EA constriction is important& beneficial in some diseases as

cirrhosis, nephrotic syndrome & congestive heart failure in which the renal blood flow & intraglomerular pressure is maintained critically by EA constriction through the effect of prostaglandins(PGs) ,so the use of PG Inhibitrss as NSAIDs ( brufen , diclofenac, etc) in these diseases may precipitate renal failure.

On the contrary EA Constriction may be harmful in other conditions as in diabetic nephropathy as the renal damage is accelerated by high intraglomerular pressure through EA constriction ,so the use of & PG inhibitors or ACEI as captopril may reduce the EA constriction ,reduce IGP & slow or reverse the renal damage in diabetic nephropathy.

Glomerular filtration & RBF autoregulation: GFR & RBF remain constant in the BP range of 75-160 mm.Hg, maintained

by 4 factors : 1.Tubuloglomerular feedback: controlled by juxtaglomerular apparatus

consisting of distal tubular cells called macula densa & AA/EF cells called juxtaglomerular cells ,so when BP is lowered causing lowering of RBF,glomerular hydrostatic pressure & GFR ,this will cause decrease Nacl delivery to the distal tubular cells (macula densa) ,this will stimulate the juxtaglomerular cells of the AA & EA to release Renin which cause release of Angiotensin1 from the liver which in turn is converted to Angiotensin 2(A2) by the enzyme Angiotensin converting enzyme secreted by the lungs & A2 is a strong vasoconstrictor causing renal arteriolar vasocosntriction specially EA vasoconstriction so maintaining glomerular hydrostatic pressure & GFR back to normal.

2.Glomerulo tubular balance & pressure diuresis by which the GFR is returned to normal when BP & RBF is increased, by increasing renal Na & water excretion (pressure diuresis) & by decreasing tubular reabsotption & vice versa.

3.Myogenic autoregulation of RBF & GFR: When the renal arteries contract in response to increase BP to protect the

renal blood flow from excess rise & vice versa dilates in reponse to low BP. 4.High protein intake & high blood glucose : which both decrease the Na

delivery to the distal tubules by increasing proximal tubule Na reabsorption, as both AA & glucose are cotransported with Na in the proximal tubules, so increase AA & glucose delivery to the proximal tubules causes increasesd reabsorption of Na & decreased delivery of Na to macula densa, so activate the juxtaglomerular apparatus mentioned above, leading to increase RBF & GFR.