The nephron is the functional unit of the kidney, which filters blood to form urine. The nephron contains a glomerulus that filters the blood and a renal tubule that reabsorbs most of the filtered water and solutes. Key functions of the nephron include filtering the blood at the glomerulus and reabsorbing various substances like water, glucose, amino acids, salts, and urea along different portions of the renal tubule under hormonal control. The kidney plays an important role in regulating fluid and electrolyte balance, excreting wastes, and producing hormones.
2. Nephron as the functional unit of kidney
⢠Nephron is the functional unit of the kidney.
⢠Each Kidney is composed of approximately one million nephrons.
⢠Nephron is made of a renal capsule and renal tubule.
⢠The renal capsule contains a thin walled sac-like structure called the Bowman's
capsule into which the afferent arterioles from renal artery form a capillary
network called glomerulus.
⢠Each renal tubule consists of Proximal convoluted tubule (PCT) which dips into
the renal medulla to form the Loop of Henle. The tubule reenters the renal
cortex to form the Distal convoluted tubule (DCT). Several DCTs merge to form
a Collecting duct.
⢠Several Collecting tubules join and open into renal pelvis . The juxtaglomerular
apparatus present between the DCT and afferent arterioles secretes renin.
3. Diagrammatic representation of Nephron
The glomerulus has a semipermeable membrane through which substances (except cells
and large molecular size plasma proteins) are filtered into Bowman âs capsule at a rate
( 120ml/minute).This is known as Glomerular filtration rate(GFR).
4. Functions of components of Nephron of kidney
âProximalconvolutedtubules(PCT):80%saltandwaterareabsorbedfromglomerular
filtrateinproximalconvolutedtubule.Allfilteredglucoseandaminoacidsarereabsorbedin
here.Lowmolecularweightproteins,urea,potassium,magnesiumandcalciumare
reabsorbedtovaryingextent.
âLoopofHenle:
⪠ThedescendingloopofHenleishighlypermeabletowater.Passivereabsorptionofwater
occursleavinghighlyconcentratedurineatthebottomofloop.
⪠TheascendingloopofHenle(dilutingsegment)isrelativelyimpermeabletopassageof
waterbutactivelyabsorbsNa+andCl- ions.
âDistalconvolutedtubule(DCT):asmallfractionoffilteredsodium,chlorideandwateris
reabsorbedinDCT, whichrespondstoADH,sothatitswaterpermeabilityishighinthe
presenceofhormoneandlowinitsabsence.
âCollectingtubule:ADHcontrolsthewaterpermeabilityofthecollectingtubulethroughout
itslength.
6. Functions of kidney
âFunctions of kidney :
1. Excretion of metabolite waste products : the end products of protein and nucleic acid
metabolism and metabolites of xenobiotics are eliminated from the body. (effect on
blood pressure and heart) e.g. urea, creatinine, creatine , uric acid , sulphate and
phosphates
2. Maintain fluid and electrolyte homoeostasis :the kidney is largely responsible for the
regulation of water, electrolyte ,acid -base balance(maintenance of pH) in the body e.g.
glucose , amino acids etc.
3. Endocrine Function: The kidneys also function as Endocrine organs by producing
hormones:
a) Renin
b) Erythropoietin (effect on RBC synthesis)
c) 1,25 Dihydroxycholecalciferol= Calcitriol (activation of Vitamin D âeffects on bones)
d) Prostaglandins (PGA 2 PGE 2 ,PGF 2ďĄ )
e) Bradykinin and Kallidin
4. Participates metabolism by retaining substances vital to body: The kidneys reabsorb and
retain several substances of biochemical importance in the body . e.g. Glucose ,amino acids .
8. The Formation of urine
⢠Three steps of formation of urine:
1. Glomerular filtration
2. Tubular reabsorption
3. Tubular secretion
9. Glomerular filtration: various ways
Complete
reabsorption
Partial reabsorption
by diffusion
No reabsorption and
no secretion
Secretion
Reference D.N. Baron
Schematic diagram
11. Endocrine Functions of the kidney
Renin: a proteolytic enzyme produced in the juxtaglomerular apparatus of the kidney . It
stimulates the formation of Angiotensin II which in turn leads to Aldosterone production.
Angiotensin II and Aldosterone are the hormones involved in the regulation of electrolyte
balance . Angiotensin II is a powerful vasoconstrictor, that increases blood pressure and
causes contraction of smooth muscles.
Erythropoietin : a peptide hormone stimulates erythropoiesis in bone marrow (hemoglobin
synthesis) .
1,25 Dihydroxycholecalciferol (Calcitriol ): 1-hydroxylation occurs in kidney to form the
biochemically active form of vitamin D (Calcitriol). It regulates calcium absorption from the
gut and homeostasis.
Prostaglandins (PGA 2 PGE 2 ,PGF 2ďĄ ): are produced by renal medulla induce relaxation of
smooth muscles, vasodilatation, decrease in renal pressure, increase in renal blood flow and
excretion of sodium.
Bradykinin and Kallidin: peptide hormones produced by the kidney. They are a powerful
vasodilators that influence reabsorption of sodium and water. Bradykinin stimulates synthesis
of renal Prostaglandins .Kinins also play a role in blood coagulation increase renal blood flow
and exhibit antihypertensive effect .
âKidney possess receptors for hormones parathyroid hormone and ADH.
âKidney possess sites of inactivation of hormones such as insulin ,glucagon.
14. Glomerular filtration
âGlomerular filtration:
â˘Glomerular filtration is Passive process that results in the formation of ultrafiltrate of
blood .This process occurs when blood is perfused through Bowmanâs capsule .
â˘Volume of blood passing through the kidneys = 1200ml/every minute(650ml plasma)
: the renal flow blood .
â˘Glomerular filtration rate (GFR ): 120 -125 ml blood (one tenth)filtered by the
Glomerulus of kidneys every minute.
â˘With normal Glomerular filtration rate (GFR)of 120 -125 ml/ minute , 175 -180 L of
the Glomerular filtrate is formed per day in an adult ,out of which only 1.5 L is
excreted as urine. Thus more than 99% of Glomerular filtrate is reabsorbed by the
kidneys.
â˘All the (unbound) constituents of plasma ,with molecular weight less than 68000
Dalton are passed into filtrate . Therefore the Glomerular filtrate is almost similar in
composition to plasma . It is a protein free and cell free filtrate of whole blood but
contains essential metabolites such as glucose and amino acids as well as waste
products (urea , uric acid and creatinine). Albuminuria is considered as earliest
manifestation of kidney dysfunction.
15. Factors affecting Glomerular filtration
â Factors affecting Glomerular filtration:
A. Renal blood flow
B. Passage of macromolecules is based on their Shape ,charge and size of molecules
to be filtered : anionic derivatives ,globular molecules of molecular weight >
68000 Dalton are retained . The sieves of glomeruli are such that hemoglobin
(molecular weight 67000) is filtered and passed into urine , while albumin is
retained in the blood .Therefore ,the earliest manifestation of abnormal renal
function is appearance of albumin in urine.
C. Molecules less than 5KD such as glucose ,creatinine , urea and electrolytes are
freely filtered by glomeruli.
D. The low molecular weight proteins are freely filtered by glomeruli ,reabsorbed
and catabolized by renal tubular cells.
E. The normal urinary protein excretion < 150 mg /24 hr.(made up of mostly Tamm
horsefall glycoprotein) .
16. Tests for measuring Glomerular filtration
1. Creatinine clearance Test
2. Urea clearance Tests
17. Glomerular filtration rate (GFR )
âA decease in the renal function is due to the loss of functional nephrons , rather
than a decease in the function of individual nephron .
âGlomerular filtration rate (GFR) : provides the most useful index for the assessment
of the severity of renal damage.
âGlomerular filtration rate (GFR) is the product of filtration rate in single nephron
and number of nephrons in both kidneys .
âFactors affecting Glomerular filtration rate (GFR):
1. Age( kidney function decline with age e.g. at 70 yr. of age , GFR < 60 ml/min in 25%
elders)
2. Sex
3. body size
4. Protein intake
5. Pregnancy
âNormal Glomerular filtration rate (GFR )= 120- 130ml/mt/1.73 M2
âSubstantial kidney damage occurs before GFR is deceased .
18. Conditions associated with decreased Glomerular filtration rate (GFR )
âDecreased GFR observed in :
a. Blood pressure < 60 mm
b. Renal calculi*
c. Enlarged prostrate *
d. Old age
*causes for obstruction to the renal flow
20. Calculation of Estimated Glomerular filtration rate (eGFR )
CockcroftâGault equation for Estimated Glomerular filtration rate (eGFR ) :
Ccr = (140 âage in years) x weight in kg ďŞ/72 x serum creatinine ď§
ďŞ ( x 0.85 in female) assuming that they have 15 % less muscle mass.
âEstimated Glomerular filtration rate (eGFR )in ml /min / 1.73 m2 : 186 x (serum
creatinine ď§ /88.4) â 1.154 x (age) â 0.203 x 0.742 (if female)
âEstimated Glomerular filtration rate (using both equations) can be used for staging
patients with chronic kidney disease neither in healthy individuals nor in children
and obese . âModification of Diet in Renal Disease âMDRD
⢠Estimated Glomerular filtration rate (eGFR ) eliminates the need for timed urine
collection.
⢠It allows a technique of estimating creatinine clearance and thereby GFR using
serum creatinine levels.
â˘ ď§ Accuracy of serum creatinine estimation is a major deciding factor in both
equations.
26. Tubular functions of Kidney
âWhen the glomerular filtrate is formed, it contains all the crystalloids of
plasma .
âTubular functions of Kidney include Reabsorption or Secretion of solutes and
Reabsorption of water from glomerular filtrate in the proximal convoluted
tubule(PCT).
âAll filtered glucose and amino acids are absorbed in PCT.
âThe descending loop of Henle is highly permeable to water .Passive
reabsorption of water occurs leaving highly concentrated urine at the bottom
of loop.
âThe ascending loop of Henle (diluting segment) is relatively impermeable to
passage of water but actively absorbs Na+ and Cl- ions.
âLow molecular weight proteins ,urea ,potassium , magnesium and calcium are
reabsorbed to varying extent.
27. Biochemical Tests measuring tubular functions
1. Determination of specific gravity ,concentrating and diluting ability of
kidney
2. Determination of serum and urine osmolarity
3. Determination urine ammonia
4. Phenolsulphonaphthalein (PSP)Test
28. Renal Tubular reabsorption
âTubular reabsorption : is an active process.
⢠The renal Tubules(Proximal convoluted tubule-PCT, Distal convoluted tubule -
DCT , Collecting tubules) retain water and most of the soluble constituents of
Glomerular filtrate by reabsorption(active or passive process) .
⢠A small fraction of filtered sodium , chloride and water is reabsorbed in the
distal tubule which responds to antidiuretics hormone (ADH) ,so that its water
permeability is high in the presence of hormone and low in its absence.
⢠ADH controls the water permeability of the collecting tubule throughout its
length of collecting tubule.
⢠The excreted urine has an entirely different composition compared to
Glomerular filtrate from which it is derived .
29. Renal threshold substances
⢠Renal threshold substances : there are certain substances in the blood whose
excretion in urine is dependent on their blood concentration. Such substances
are referred as Renal threshold substances.
⢠At normal concentration in the blood , they are completely reabsorbed by
kidneys, with a result that their excretion in urine is almost negligible.
⢠But when the blood levels are elevated ,the tubular reabsorption capacity is
saturated ,so that excess will be excreted in urine.
⢠High threshold substances : they are reabsorbed efficiently by kidneys (e.g .
Glucose, Amino acids)
⢠Low threshold substances : they are not reabsorbed or reabsorbed slightly by
kidneys (e.g. Creatinine, Urea , Uric acid) .
30. Threshold value-Plasma levels of common substances excreted in urine
Substance Threshold value plasma levels
Glucose 180mg/dl
Lactate 60 mg/dl
Bicarbonate 28 mequ /L
Calcium 10mg/dl
The Renal Threshold of substance is the Plasma levels above which compound is excreted
in urine.
31. Role of proximal convoluted tubule (PCT) in Renal Tubular functions
Reabsorption in proximal convoluted tubule of
99 % water ( obligatory )
Uric acid (obligatory)
Sodium -Na âş (85% reabsorption)
Chloride- Cl- (85% reabsorption)
Bicarbonates (85% reabsorption)
Potassium- K âş (100% reabsorption)
Glucose (100% reabsorption)
Amino acids (100% reabsorption)
Urea/phosphates - PO âťâ´ / Calcium Ca 2+ : are partially absorbed
Secretion in proximal convoluted tubule of : Hâş ,acids , bases, NH4âş , Diodrast, PAH
32. Role of loop of Henle in Tubular functions of kidney
Reabsorption of ions in loop of Henle include :
Sodium -Na âş
Chloride- Cl-
Calcium â Ca2+
Magnesium - Mg2+
33. Role of distal convoluted tubule (DCT) in Tubular functions
Reabsorption in distal convoluted tubule include:
water (facultative)
Sodium -Na âş
Chloride- Cl-
Secretion in proximal convoluted tubule of : Hâş , Potassium- K âş , NH4âş , Uric acid
34. Tubular reabsorption Function of kidney
âReabsorption of water:
⢠More than 99 % of water (187.5 liters/day) is reabsorbed by counter
current multiplication or counter current exchange .
⢠Reabsorption of water from distal convoluted tubule (DCT) and
collecting ducts is facilitated by the pituitary hormone ADH.
âReabsorption of sodium: by symport and antiport system.
âReabsorption of potassium: occurs in the proximal convoluted
tubule (PCT).
⢠Reabsorption of urates: occurs in the proximal convoluted tubule
(PCT) by both active and passive transport.
36. Renal Tubular reabsorption of water
⢠More than 99% of water entering in Renal Tubules is reabsorbed .
âReabsorption of water in the PCT :
1. About 80% of water is reabsorbed .
2. Water is reabsorbed by passive transport as a solvent for actively reabsorbed sodium,
chloride , bicarbonate ions and glucose (obligatory Reabsorption âwater has to move
along with solutes to maintain osmalality).
3. Tubular filtrate is isosmotic with plasma.
âReabsorption of water in the descending limb :
1. Tubular filtrate is hyperosmotic with plasma.
2. Water without solute is lost . This is termed as counter current multiplication .
3. Counter current multiplication :
a. Functions in absence of antidiuretic hormone( ADH)
b. is an active process that creates high medullary osmality in the Renal medulla and
produces dilute urine .
âReabsorption of water in the ascending limb :
a. sodium chloride is lost without water .
b. Tubular filtrate is hypoosmotic with plasma.
37. Flow rates of Renal Tubular reabsorption of water
Water reaches Flow rate Osmolarity
Proximal convoluted tubules 125 ml /min sodium, chloride ,
bicarbonate ions and glucose
are absorbed. Water has to
move along with solutes to
maintain osmality-
obligatory Reabsorption
Loop of Henle 25 ml/min Sodium is reabsorbed, Water
reabsorption is less. Urine is
hypotonic.
Distal tubules 16 ml/min Water reabsorbed under
influence of ADH âfacultative
reabsorption
Collecting tubules 1 ml/min Urine is hypertonic.
38. Countercurrentmechanismof RenalTubularreabsorptionofwater
âReabsorption of water in the DCT and the collecting duct :
1. Water without solute is reabsorbed along the gradient created by counter
current multiplication .
2. This is termed as counter current exchange .
3. Counter current exchange :
a. is facilitated by antidiuretic hormone(ADH). ADH secretion in turn, is
controlled by hypothalamic osmoreceptors. The osmolality of plasma is the
stimulus for modulating ADH secretion.
b. concentrates the urine.
39. Factors influencing ADH secretion
âFactors influencing ADH secretion include :
⢠Osmotic pressure of the blood: Osmoreceptors in the hypothalamus that are
sensitive to changes in the Osmotic pressure of the blood influence the
synthesis and secretion of ADH.
⢠Blood volume: volume receptors in the carotid sinus and left atrium
influence ADH secretion.
⢠An increase in Osmotic pressure of the blood or decrease in blood volume
stimulates ADH secretion.
40. Osmoreceptors in the hypothalamus
Osmoreceptors in the hypothalamus that are sensitive to changes in the Osmotic pressure of
the blood influence the synthesis and secretion of ADH.
41. Renal Tubular reabsorption of sodium
⢠Tubular reabsorption of sodium occurs in Proximal convoluted tubule-PCT by two
types of cotransport systems.
âSymport system :which involves cotransport of sodium along with other substances
such as glucose ,amino acids and phosphates .It is catalyzed by Na+ _ K + ATP ase
present in basolateral plasma membrane of the epithelial cells .
⢠This creates sodium gradient that accomplishes active transport of sodium out of
the cell while potassium enters the cell.
⢠There is passive transport of equivalent amount of chloride to maintain electrical
neutrality.
⢠The net effect is the reabsorption of sodium chloride along with glucose and amino
acids etc.
âAntiport system : involve exchange of sodium (reabsorbed) for another cation such
as H + as in Na+ -H +. This also achieves a net reabsorption of bicarbonate. When
hydrogen ions are to be conserved ,sodium to potassium exchange occurs .
42. Symport system for Renal Tubular reabsorption of sodium
Symportsystem:whichinvolvescotransportofsodiumalongwithothersubstancessuchasglucose,amino
acidsandphosphates.Itis iscatalyzedbyNa+ âK+ ATPase presentinbasolateralplasmamembraneofthe
epithelialcells.
43. Renal Tubular reabsorption of Glucose
⢠Normally Glucose is reabsorbed completely .
⢠The maximum rate at which Glucose is reabsorbed , referred as the Tubular
maximum for glucose(TmG)= 350 mg/min.
⢠When blood Glucose exceeds renal threshold for Glucose which is 10mmols/L
or (180mg/dl) , glucose spills over into the urine (glycosuria) .
⢠Water is excreted as a solvent for glucose (osmotic diuresis).
44. Renal Tubular reabsorption of Calcium
âTubular reabsorption of Calcium :
⢠About 90% of Calcium is reabsorbed from the glomerular filtrate.
⢠Regulation of calcium balance is achieved at the distal convoluted tubule .
⢠Factors regulating calcium reabsorption: parathyroid hormone and vitamin D.
45. Renal Tubular reabsorption of Uric Acid
⢠Uric Acid is completely reabsorbed in Proximal convoluted tubule-PCT, by both
active and passive mediated process .
⢠There is an active secretion of Uric Acid in the tubules . About 85% of the
excreted Uric Acid is derived by tubular secretion.
⢠The drug ,probenecid is secreted by the tubules and competes with Uric Acid
for reabsorption . Since probenecid increases Uric Acid excretion ,it is
uricosuric.
46. Renal Tubular reabsorption of Urea
⢠Urea is freely filtered by the glomerulus ,but about the 40% is reabsorbed
actively by the tubules.
⢠Rate of reabsorption of Urea varies inversely with tubular flow and accounts for
the elevation of blood urea when renal function is low.
⢠Concentration of Urea in urine = 70x concentration of Urea in plasma
⢠Urea forms 80% of total urinary solutes .
⢠Urine is roughly a 2 % solution of Urea.
47. Renal Tubular reabsorption of Potassium
⢠70% of potassium in glomerular filtrate is reabsorbed by Proximal convoluted
tubule-PCT.
⢠Net secretion of potassium at the distal tubules ,in exchange for sodium
reabsorption , under the effect of aldosterone.
⢠However when H + concertation is increased, H + ions are exchanged for
sodium instead of potassium.
48. Mechanism of action of diuretics :1
Diuretics Mechanism of action of diuretics Site of action
Mannitol Osmotic diuretics act by interfering with reabsorption
of solutes so that more water is obligatory excreted
along with the solutes .
PCT
Acetazolamide A carbonic anhydrase inhibitor-the dissociation of
H2CO3 to H2O and CO2 is inhibited âdecreased
reabsorption of bicarbonate ,sodium and water .
PCT
Thiazide decreased reabsorption of sodium and more water is
excreted obligatorily .
DCT
Frusemide Inhibits reabsorption of chloride , sodium and water
(chances for potassium depletion) .
Ascending limp of
loop of Henle
Spironolactone
(K+ sparing )
Aldosterone antagonist DCT
51. Reabsorption ,secretion and excretion of substances by kidney
Parameter Reabsorption Secretion Excretion/relative
concentration
Creatinine Nil Nil GF = URINE
Uric acid 70 % by proximal
convoluted tubules
(PCT)
by distal convoluted
tubules( DCT)
GF ď URINE
Urea 40 % by PCT Nil GF > URINE
Sodium ( Na âş) Partial Nil GF > URINE
Glucose Complete Nil GF >> URINE
Amino acids Complete Nil GF >> URINE
52. Tubular maximum
⢠Tubular maximum (Tm): is used to indicate maximum capacity of kidneys to
absorb a particular substance .
⢠e.g. Tubular maximum for glucose (TmG) : 350 mg/min
53. Defects in Renal Tubular reabsorption
⢠Renal glycosuria in which glucose appears in urine despite of normal plasma
glucose levels .
⢠Vitamin D resistant rickets : in which phosphates reabsorption is defective .
⢠De Toni Fanconi syndrome: is associated with glycosuria, phosphaturia and
Renal Tubular acidosis.
⢠Renal Amino aciduria : as in Fanconi syndrome and cystinosis .
55. Tubular secretion in kidney
âTubular secretion in kidney :
âsubstances actively secreted by renal tubular cells include:
a) Endogenous substances( e.g. hippuric acid ,bile salts ,urates)
b) Exogenous substances( e.g. diuretics , salicylates ,p- amino Hippurate,
penicillin )
â Creatinine : is secreted when plasma levels increase above normal levels .
âPotassium : is secreted in the DCT in exchange for sodium reabsorbed.
âAldosterone favors sodium reabsorption and excretion of Potassium.
âPrimary aldosteronism (excessive Aldosterone) : there is excessive excretion
of Potassium and retention of sodium.
âAddisonâs disease (deficiency of Aldosterone) : sodium excreted and
Potassium retained in excess .
58. Tubular secretory mass in kidney
⢠Tubular secretory mass : mass of functioning Tubular mass can be assessed
by measuring the tubular maximum for PAH(Tm PAH).
Tm = UV/P X GFR
For PAH ,the Tm is 76 mg/minute.
59. Tubular Dysfunctions of Kidney
âIn Tubular Dysfunctions of Kidney:
1. Urine volume increases
2. Urine concentration decreases
3. Specific gravity decreases
4. Serum uric acid increases (uric acid excretion decreases)
5. Acidification of urine decreases
6. Amino aciduria present
7. Serum phosphate decreases
8. Urine dilution test abnormal