renal system is very imlortant system

1. Renal physiology
DR IBRAHIM ALGUBANI
PHYSIOLOGY DEPARTMENT

2. The renal system is composed of the following:
• 2 Kidneys. • 2 Renal pelvises. • 2 Ureters. • Urinary bladder. • Urethra.

4. The nephron
It is the functional unit of the kidney. Each human kidney contains about 1
million nephrons.

5. The nephron is composed of the following:
A- Renal corpuscle (glomerulus). It is composed of:
1- Glomerular capillary. 2- Bowman’s capsule.
B- Renal tubules: they include: [Proximal convoluted tubules / Loop of Henle /
Distal convoluted tubules / Collecting ducts].

6. 1- Proximal convoluted tubule (PCT): It is lined by single layer of cuboidal cells
that show brush luminal border [due to microvilli that increase the surface
area 20 times]. At their basal borders, these cells have many mitochondria that
provide the energy for active transport.

7. 2- Loop of Henle: It is composed of ascending & descending limbs. The
ascending limb composes of:
a- Thin segment: it’s the lower part of the ascending limb. It is made up of
flattened cells [like the descending limb].
b- Thick segment: it is the upper part of the ascending limb of loop of Henle. It
is [like other parts of the nephron] is made up of cuboidal cells.

8. 3- Distal convoluted tubules (DCT): The cells of DCT have fewer microvilli.
Functionally, it is divided into:
a- First half: it is similar in structure & function to the thick part of ascending
limb of loop of Henle, and it is called the diluting segment of DCT.
b- Late (second) half.

9. 4- Collecting ducts (CD): Each group of DCTs collect together to form collecting
duct that pass through the renal cortex and medulla to empty the formed
urine at the apex of medullary pyramids into the renal pelvis. Functionally, the
CD is divided into [cortical & medullary] collecting ducts.

10. • The nephrons are of 2 types [cortical & juxtamedullary]

12. Renal circulation
In the renal circulation, there are 2 capillary beds:
1- Glomerular capillaries: they have high pressure [60 mmHg]. This is because
the blood comes from wide arteriole (afferent) and leaves through narrow
arteriole (efferent). Due to its high pressure, they act as arterial end of usual
capillaries [site of filtration].

13. 2- Peritubular capillaries: they have low pressure [13 mmHg]. Due to its low
pressure, they function as venous end of the usual tissue capillaries
[reabsorption of fluids from the tubular lumen].
Note: the blood supply to the medulla is derived from the vasa recta. Because
the vasa recta are long straight capillary loops, hence the blood flow to the
medulla is slow and little in amount [only 1 – 2 % of total renal blood flow]
compared with that of cortex.

15. Renal blood flow
The renal blood flow = 1200 ml blood/minute [650 ml plasma/min]. The renal
fraction is the fraction of cardiac output that passes through kidneys which is:
=
𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟 𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏 𝑓𝑓𝑓𝑓𝑓𝑓𝑓𝑓 (1200)
𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜 (5000)
= 20-25%

16. Juxtaglomerular apparatus
This apparatus lies at the area of contact between the DCT and the [afferent &
efferent] arterioles of the same nephron. [See the figure].

17. The JG apparatus is composed of:
1- Macula densa cells: these cells are denser than other tubular cells. They lie
at the DCT side of the JG apparatus. They function as receptors that detect the
changes in NaCl concentration in the tubular fluid.
2- Juxtaglomerular (JG) cells: they are swollen smooth muscle cells of the
arterioles [mainly afferent]. Their function is the secretion of renin.

18. General function of the kidney
1- Plays a major role in the maintenance of homeostasis through the formation
of urine.
2- The kidney has secretory [endocrine] function where it secretes:
a- Renin: it is secreted from the JG cells. The renin has important role in
the regulation of arterial blood pressure. Its secretion is regulated by many
factors that include:
i- ↓ NaCl concentration in tubular fluid → stimulates macula
densa cells which will stimulate the JG cells to secrete renin.

19. ii- ↓ Blood pressure in afferent arterioles → stimulates the JG cells to
secretes renin [the JG cells acts as baroreceptors].
iii- the sympathetic stimulation directly stimulates the JG cells to
secretes renin.

21. b- Erythropoietin: it is secreted in response to hypoxia. It stimulates
the production of RBCs in bone marrow [stimulates erythropoiesis].
c- Active form of vitamin D: it ↑ Ca+ absorption from GIT and ↑ its
deposition in bone.

22. Mechanism of urine formation:
The urine is formed by 3 main processes:
1- Glomerular filtration.
2- Tubular reabsorption.
3- Tubular excretion.

23. Glomerular filtration
Definition: it is the filtration of fluid from the blood in glomerular capillaries to the cavity of
Bowman’s capsule due to pressure difference.

24. Glomerular filtration rate (GFR)
It is the volume of fluid filtered in all nephrons of both kidneys each minute. In
average sized normal man, the GFR = 125 ml/min [180 liters/day]. This value is
10% lower in females.
The glomerular membrane is characterized by its high degree of selectivity for
passing of molecules:

25. 1- Molecules with MW 10,000 or less pass freely through the membrane.
2- Molecules with MW more than 10,000, their permeability are inversely
proportional to their MW.
3- Molecules with MW more than 80,000 can not pass through the
membrane.

26. Notes:
• The glomerular membrane has proteins that have strong negative charge.
This negative charge will repeal the other negatively charged proteins in the
plasma [e.g. albumin] and prevent their filtration even if their MW was less
than 80,000.
• The glomerular filtrate is composed of plasma minus plasma proteins
[despite it contains trace amount of albumin (0.5% that of plasma)].

27. Filtration fraction
It is the fraction of renal plasma flow that becomes glomerular filtrate.
Filtration fraction =
𝑮𝑮𝑮𝑮𝑮𝑮
𝑹𝑹𝑹𝑹𝑹𝑹
+
𝟏𝟏𝟏𝟏𝟏𝟏
𝟔𝟔𝟔𝟔𝟔𝟔
+
𝟏𝟏
𝟓𝟓
OR 20%

28. Filtration forces
The filtration of plasma through the glomerular membrane depends on many
forces that may (Help) or (Oppose) this process.

29. • Forces that help the filtration:
1- Glomerular capillary hydrostatic pressure [60 mmHg].
2- Osmotic pressure in Bowman’s capsule [normally = zero].

30. • Forces that oppose the filtration:
1- Osmotic pressure of Pl.Pr in the glomerular capillary [32 mmHg].
2- Pressure in Bowman’s capsule [18 mmHg].
The net filtration pressure = (60 + 0) – (32 + 18) = 60 – 50 = 10 mmHg.

31. Filtration coefficient ( Kf)
It is the GFR if the filtration pressure was 1 mmHg.
Kf =
𝑮𝑮𝑮𝑮𝑮𝑮
𝒇𝒇𝒇𝒇𝒇𝒇𝒇𝒇𝒇𝒇𝒇𝒇𝒇𝒇𝒇𝒇𝒇𝒇𝒇𝒇 𝒑𝒑𝒑𝒑𝒑𝒑𝒑𝒑𝒑𝒑𝒑𝒑𝒑𝒑𝒑𝒑
=
𝟏𝟏𝟏𝟏𝟏𝟏
𝟏𝟏𝟏𝟏
= 12.5 ml

32. Factors affecting GFR
1- Glomerular capillary pressure: the ↑ in glomerular capillary pressure → ↑
GFR and vice versa. This pressure could be affected by the following:
a- Renal blood flow: ↑ RBF → ↑ glom. Cap. Pressure.
b- Diameter of afferent arteriole: dilatation → ↑ glom. Cap. Pressure. and the
constriction has reverse effect.

33. c- Diameter of efferent arteriole:
• Dilatation → ↓ gl. Cap. Pr.
• Mild constriction → slight ↑ in GFR.
• Moderate & sever vasoconstriction → ↓ GFR.
d- Sympathetic stimulation → constriction of afferent arteriole → ↓glo.cap.pr
→ ↓ GFR.

34. 2- Osmotic pressure in Bowman’s capsule: when the proteins filtrate to the
Bowman’s capsule [does not happen normally, but in kidney disease], these
proteins will ↑ the osmotic pressure in Bowman’s capsule → ↑ GFR.
3- Osmotic pressure of plasma proteins: in hypoproteinemia [↓ Pl.Pr in
plasma] → ↓ plasma osmotic pressure → ↑ GFR.

35. 4- When the urinary tract get obstructed [e.g. stone in ureter], this will ↑ the
hydrostatic pressure in the Bowman’s capsule → ↓ GFR.
5- Glomerular membrane surface area & glomerular permeability: if one or
both of them ↓ (that is mean ↓ Kf ) → ↓ GFR, and vice versa.

36. Measurement of GFR
The GFR is measured by the plasma clearance concept. The plasma clearance
of any substance means the volume of plasma cleared from this substance per
minute.
• For example: if we said the plasma clearance of substance X = 50 ml/min,
that is mean, the kidneys clear 50 ml of plasma that contain substance X in
each minute. The clearance of any substance is calculated as the following:
C=
𝑼𝑼𝑼𝑼𝑼𝑼
𝑷𝑷

37. • The GFR is measured by the clearance of exogenous substance (normally not
present in the body) called inulin. This is because the inulin has the following
characters: 1- Freely filtered through the glomerular membrane [it MW =
5000]. 2- Neither reabsorbed nor secreted by the renal tubules.
• Clinically, the clearance of another endogenous substance (normally present
inside the body) called Creatinine, is used in the measurement of GFR by the
clearance concept.

38. Measurement of renal plasma flow
The renal plasma flow can also be measured by the plasma clearance concept.
But in this case, the substance used [Para-Amino Hippuric acid (PAH)] should
have another characters (unlike in measurement of GFR). The characters of
PAH include:
1- Freely filtered.
2- Not reabsorbed.
3- Completely secreted.

39. Renal physiology
DR IBRAHIM ALGUBANI
PHYSIOLOGY DEPARTMENT

40. Tubular reabsorption
I- Reabsorption of organic substances
Glucose reabsorption
The glucose is completely reabsorbed in the PCT.
• At luminal border: the glucose is transported by secondary active transport
[co-transport with Na+].
• At basal border: it is transported passively by facilitated diffusion.

42. Tubular load
• It is the amount of substance filtered with GFR / minute. If the GFR = 125
ml/min, and plasma glucose = 100 mg% (1 mg/ml):
Tubular load of glucose = GFR X glucose in each ml of GFR = 125 X 1 = 125
ml/min. That is mean, the kidneys filtrate 125 ml of glucose per minute.

43. • The kidney can reabsorb a maximum amount of glucose up to 320 mg/min
[which correspond with plasma glucose = 225 mg% (125 X 2.55)]. If the tubular
load (reabsorption) exceeded this limit, the excess glucose will not be
absorbed and will be excreted in urine.
• The glucose start to appear in urine when the plasma glucose level = 180
mg/dL. This limit called the renal threshold for glucose.
• Glucosuria: it is the presence of glucose in urine. It usually occurs when the
blood glucose level exceeds the renal threshold (180 mg %) [As in case of
diabetes mellitus].

44. Amino acids reabsorption
The amino acids (like glucose) are completely reabsorbed at PCT by:
• Co-transport with Na+ (at luminal border).
• Passively by facilitated diffusion (at basal border).
Amino aciduria: it is the presence of amino acids in urine.

45. Protein reabsorption
Normally a trace amount of albumin is filtered (30 mg/day) which is
completely reabsorbed by pinocytosis.
Uric acid reabsorption
90% of the filtered uric acid is reabsorbed actively at PCT, only 10% is excreted
in urine.

46. Urea reabsorption
About 50% of the filtered urea is reabsorbed and the other 50% is excreted.
The urea reabsorption take place in PCT & medullary collecting ducts after
water reabsorption [the urea diffuses passively following water reabsorption].

47. The rate of urea excretion is affected by:
a- ↑ Plasma urea → ↑ tubular load → ↑ urea excretion.
b- ↑ GFR → ↑ tubular load → ↑ urea excretion.
c- ↑ reabsorbed H2O → ↑ urea concentration in tubular fluid → ↑ urea
reabsorption → ↓ urea excretion.

48. Urea cycle
• The urea reabsorbed in medullary collecting ducts (50% of filtered urea) pass
through medullary interstitium to be secreted at lower thin part of loop of
Henle. This secreted amount of urea will be added to the (50% of filtered urea)
that is escaped the reabsorption at PCT.
• Then, this mixture of urea [50% escaped & 50% secreted] will pass through
the [thick part of loop of Henle, DCT, and cortical collecting ducts] without
reabsorption [because these parts are impermeable to urea] until reach back
to medullary collecting ducts where part of this urea will be reabsorbed again
in the same cycle.
• The urea cycle keeps the urea in high concentration in the renal medulla
[shares in Medullary Hyperosmolarity].

49. II- Reabsorption of inorganic substances
Sodium reabsorption
Normally,99% of filtered Na+ is reabsorbed actively.

51. 1- At luminal border: it is transported passively by facilitated diffusion mainly
through carrier proteins which play a very important role in secondary active
transport of different substances.
2- At basal border: it is transported actively by Na – K+ pump.

52. Secondary effects of Na+ reabsorption
1- At PCT: 65% of the Na+ is reabsorbed actively at PCT. Secondary to its
absorption at this area:
a- Glucose, amino acids, K+ and Ca++ are reabsorbed by co-transport.
b- Cl- and HCO3- are reabsorbed passively due to electrical gradient.
c- H2O is reabsorbed passively by osmosis [due to osmotic effect of
reabsorbed Na+].
d- H+ is secreted by counter transport.

53. 2- At the loop of Henle: 27% of filtered Na+ is reabsorbed at this area.
a- The descending limb is impermeable to Na+ (no Na+ reabsorption).
b- At thin part of ascending limb, the Na+ is reabsorbed passively.
c- At thick part of ascending limb the Na+ is reabsorbed actively in co-
transport with K+ & Cl- [1Na+, 1K+, 2 Cl- in co transport].

54. 3- At second ½ of DCT & CD: About 8% of the filtered Na+ reaches this area.
Variable amount of this Na+ is reabsorbed actively at this area according to the
body needs under the control of aldosterone hormone. Secondary to the Na+
reabsorption at this area:
a- Cl- & HCO3- are reabsorbed passively due to electrical gradient.
b- K+ is secreted coupled with Na+ [Na+ – K+ exchange site].

55. Factors affecting Na+ excretion
1- Change in GFR: change in GFR leads to minimal change in Na+ excretion due
to glomerular balance mechanism [when the GFR ↑ → ↑ Na+ reabsorption
(the exact mechanism unknown)].
2- Effect of hormones:
a- Aldosterone [the most important hormone] leads to ↑ Na+ reabsorption
and K+ secretion mainly at DCT & CD.
b- Angiotensin II ↑ Na+ reabsorption either by direct effect on renal tubules or
indirectly through stimulation of aldosterone secretion.
c- Circulating epinephrine ↑ Na+ reabsorption during sympathetic stimulation.

56. d- Glucocorticoids (cortisone) when present in high level in blood → ↑ Na+
reabsorption.
e- Estrogen [which ↑ during pregnancy] → ↑ tubular Na+ reabsorption.
f- Atrial natriuretic hormone: it is a polypeptide secreted mainly from the right
atrium of the heart. It is secreted in response to atrial stretch [e.g. ↑ blood
volume]. It increases the Na+ [thus water] excretion by:
i- ↓ Na+ tubular reabsorption.
ii- ↓ aldosterone release.

57. 3- H+ secretion:
In the case of acidosis, there is ↑ in H+ secretion.
This will lead to ↑ Na+ reabsorption due to:
a- Counter transport of Na+ with H+.
b- In response to electrical gradient created by secreted H+.
The opposite occurs during alkalosis [when the H+ secretion↓].

58. 4- K+ secretion: ↑ K+ secretion [in Hyperkalemia] → ↑ Na+ reabsorption →
↓ Na+ excretion, and vice versa.
5- Diuretics: most of diuretics ↓ Na+ reabsorption and ↑ its excretion [this
will ↑ water excretion (diuresis)].

59. Potassium reabsorption
The filtered potassium is reabsorbedcompletely at PCT and thick part of
ascending limb of loop of Henle by co transport with Na+.
But it is secreted at late distal tubules and cortical collecting ducts in exchange
with Na+.
Note: the K+ secretion is the function of special cells called principal cells
which are present only in late DCT and cortical CD [K+ secretion sites]. They
have this ability because their luminal border is very permeable to K+ [in
contrast to the epithelial cells elsewhere in renal tubules].

61. Factors affecting K+ excretion
1- ↑ Plasma K+ level (Hyperkalemia) → ↑ rate of its secretion [hence its
excretion].
2- Aldosterone → ↑ K+ secretion as a result of ↑ Na+ – K+ pump.
3- H+ secretion: there is reciprocal relation between K+ & H+ secretion. For
example: when there is ↑ H+ secretion [as in acidosis], the K+ secretion ↓ →
Hyperkalemia. The opposite occurs during alkalosis.
4- Diuretics: all diuretics that inhibit Na+ reabsorption in PCT and loop of Henle
[e.g. frusemide & thiazides] → ↓ Na+ – K+ exchange → ↓ K+ secretion and
excretion.

62. Chloride reabsorption
More than 99% of the filtered Cl- is reabsorbed [mainly passively].

63. 1- At PCT: Cl- passively reabsorbed secondary to Na+ reabsorption.
2- At loop of Henle: a- Descending part: not permeable to Cl- [no
reabsorption]. b- Ascending part:
i- Thin part: passively [like Na+].
ii- Thick part: actively [1Na+, 1K+, 2Cl- co-transport].
3- Late DCT & CD: passively secondary to Na+ reabsorption [electrical
gradient].

64. Bicarbonate reabsorption
More than 99% of filtered HCO3- is reabsorbed mainly at PCT in coupling with H+ secretion by
the aid of carbonic anhydrase enzyme as in the figure.

65. But if the filtered HCO3- was more than available secreted H+, then the excess
HCO3- will be excreted in the urine.
Note: there is an inverse relation between Cl- reabsorption & HCO3-
reabsorption [i.e. ↑ Cl- reabsorption → ↓ HCO3- reabsorption]. This explains
the inverse relation between plasma Cl- & plasma HCO3- concentrations [to
keep the total anion concentration constant].

66. Phosphate reabsorption
About 90% of filtered phosphate is reabsorbed actively mainly at PCT. The
parathormone ↓ phosphate reabsorption → ↑ its excretion and ↓ its plasma
level.

67. Water reabsorption
Normally, more than99% of filtered water is reabsorbed by osmosis in 2 main
parts:
A- PCT: in the PCT, the water reabsorption has the following characteristics:
1- Fixed fraction is reabsorbed (65%) regardless of body needs [obligatory
water reabsorption].
2- Reabsorbed by osmosis secondary to Na+ reabsorption.
3- The water is reabsorbed with an equivalent amount of Na+, so it has the
same osmolarity as plasma (iso-osmotic). [i.e. it does not affect plasma or
tubular osmolarity and has no relation to excretion of diluted or concentrated
urine].

68. B- Late DCT & CD: the reabsorption of water at these sites is characterized by:
1- Variable amount is reabsorbed according to body needs [facultative water
reabsorption].
2- It is independent on Na+ reabsorption but depends on:
a- Anti diuretic hormone (ADH): it increases the permeability of DCT &
CD to water by opening the door for its reabsorption [DCT & CD are not
permeable to water except under the effect of ADH].
b- Medullary hyperosmolarity: it is the power that pulls the water.
3- Pure water is reabsorbed without accompanied Na+ [hypo-osmotic fluid] which
will ↓ plasma osmolarity & ↑ tubular fluid osmolarity [this area determine the
secretion of diluted or concentrated urine].

70. Medullary Hyperosmolarity
• In the medulla, there is a longitudinal hyperosmotic gradient. The superficial
layers of medulla are iso-osmolar [300 m.osmol/L] and the osmolarity increase
gradually until reach its maximum at the tip of medullary pyramids [1200
m.osmol/L (4 times that of plasma)].
• The medullary hyperosmolarity is created by:
A- Urea cycle [discussed before].
B- Counter current mechanism.

71. Counter current mechanism It is done by:
1- Counter current multiplier [by long loop of Henle of juxtamedullary
nephrons].
2- Counter current exchanger [by vasa recta].

73. Counter current multiplier
The long loop of Henle of juxtamedullary nephrons creates a medullary
hyperosmotic gradient longitudinally along the different layers of medulla.
This is done as the following:
1- The fluid in the proximal convoluted tubules is iso-osmolar [300 m.osmol/L]
[because the water is reabsorbed with equivalent amount of Na+ (solute)].
2- The descending limb of loop of Henle is freely permeable to water and
impermeable to [Na Cl]. So, as the fluid descend down in the descending limb,
it looses more and more water → the tubular fluid will becomes hyper-osmotic
more and more while we descend until reach its maximum osmolarity at the
end of the loop [about 1200 m.osmol/L].

74. 3- The fluid which will pass in the ascending limb of loop of Henle is hyper-
osmotic [about 1200 m.osmol/L], and the ascending limb is impermeable to
water, and permeable to Na Cl which will pass passively [in the thin part of
ascending limb] and actively [in the thick part of ascending limb]. This will lead
to transport of solutes only [Na Cl] from the tubules into the medullary
interstitium without accompanied transport of water.

75. 4- As a result, the tubular fluid will become hypo-osmotic as it passes up in the
ascending limb till it reaches its lowest osmolarity in the nephron at the tip of
the ascending limb [100 m.osmol/L].
5- All the mentioned mechanisms will make a small difference transversely
[200 m.osmol/L] and a big longitudinal difference [about 900 m.osmol/L].
6- The interstitial fluid of the medulla will equilibrate osmotically with the fluid
in the descending limb. So, the osmolarity in the superficial layers of the
medullary interstituim is [300 m.osmol/L] and of the deep layers is [1200
m.osmol/L].

76. Counter current exchanger
The vasa recta keeps thehyperosmolarity created by loop of Henle by trapping
solutes [Na Cl & Urea] in renal medulla and prevent their removal by
circulation. This is done by the following mechanisms:
1- in the descending limb of vasa recta:
a- Na Cl passes from medullary inerstitium into blood.
b- Water passes from blood into medullary interstitium.
2- In the ascending limb of vasa recta, the opposite occurs:
a- Na Cl passes from blood into medullary interstitium.
b- water passes from interstitium into blood → circulation.

77. Osmolarity in different segments of the
nephron

80. Diluting ability of the kidney
It is the ability of the kidney to excrete large amount of diluted urine (diuresis).
It depends mainly on ↓ ADH level in the plasma.
It is tested by water loading test [drinking large quantity of water → excretion
of diluted urine with osmolarity less than (100 m.osmol/L) within 4 hours].

81. Concentrating ability of the kidney
It is the ability of the kidney to excrete small amount of concentrated urine
[antidiuresis]. It depends on both Medullary hyperosmolarity & ↑ ADH
plasma level.
It is tested by water deprivation test [patient doesn’t take water for 12 hours
→ by the end of this period, the urine should be concentrated with osmolarity
exceeds 900 m.osmol/L.

82. Osmolar clearance and free water
clearance
Clearance of osmolar substances is calculated as clearance of a single
substance.

83. Free water is the excess water that is excreted thanosmolar substances, and
the plasma volume cleared from this excess water each minute is called free
water clearance. Free water clearance = urine volume per minute – osmolar
clearance. Free water clearance can either be
1- Positive: when excess H2O is removed from plasma [urine is diluted >
plasma].
2- Negative: excess solutes are removed [urine is concentrated].
3- Zero: that is mean the osmolarity of urine equals the osmolarity of plasma
[solutes removal = water removal].

84. Diabetes insipidus
It is a disease characterized by:
• Polyurea [passage of large amount of diluted urine].
• Polydepsia [excessive drinking].
• ↑ BMR. It is may be caused by deficiency of ADH (Neurogenic diabetes
insipidus) or due to failure of the kidney to respond to normal ADH
(Nephrogenic diabetes insipidus).

85. Diuretics
Diuretic: it is the substance that increases the rate of urine output [cause
diuresis]. They reduce the total amount of fluid in the body so that they are
used in treating edema & hypertension.
Types of diuretics
1- Water: drinking large mount of water → ↓ plasma osmolarity → ↓ ADH
secretion → ↓ water reabsorption at distal part of nephron → diuresis.

86. 2- Osmotic diuretics: Injecting the body with substances that are filtered but
poorly reabsorbed [e.g. Mannitol and related Polysaccharides] will lead to:
a- ↓ H2O reabsorption mainly in the PCT due to their osmotic effect.
b- ↓ H2O reabsorption → dilution of Na+ in tubular fluid → ↓ Na+
reabsorption [due to change in concentration gradient]. Thus, more Na+ will
remains in tubules and H2O will remains with it.
c- ↓ Medullary hyperosmolarity [due to ↓ solute reabsorption] → ↓ H2O
reabsorption in distal part of the nephron.

87. 3- Loop diuretics: They are the most powerful diuretics [e.g. frucemide (lasix) ].
They cause as much as 25% of GFR to pass in urine.
They inhibits the active reabsorption in the ascending limb of loop of Henle
[i.e. they inhibit Na+, K+, Cl- co-transport in the thick part of ascending limb].
This will lead to ↑ solute delivery to the distal nephron [act as osmotic agents]
& ↓ Medullary hyperosmolarity. Both of these effects → ↓ H2O reabsorption.

88. 4- Inhibitors of active reabsorption in DCT:
They inhibit the Na+, K+, Cl- co-transport in early DCT [thiazides (e.g.
chlorothiazide)].
5- Aldosterone antagonists:
• They are called K+ retaining natriuretics [e.g. spironolactone].
• They act by competitive inhibition of aldosterone → ↓ Na+ reabsorption &
↓ K+ secretion in distal nephron.

89. 6- Carbonic anhydrase inhibitors: [e.g. acetazolamide (Diamox)], they ↓ HCO3-
& H+ secretion → ↑ Na+ & K+ excretion
7- ADH receptors antagonists: They inhibit the action of ADH (vasopressin) on
V2 vasopressin receptors in renal tubules at collecting ducts.
Note: when the plasma glucose concentration increases many times → filtered
→ excreted in urine and acts as osmotic diuretic.

90. Tubular secretion
H+ tubular secretion
The H+ is secreted actively by2 different mechanisms:
1- Secondary active transport: it is the function of normal tubular cells. More
than 95% of the H+ is secreted at PCT, thick part of ascending Limb & early
distal tubule by counter transport with Na+.
2- Primary active transport: it is the function of special cells called intercalated
cells [dark cells] that constitute 10% of cells in late DCT & CD.

92. Reactions of secreted H+
Nearly most of the secreted H+ react with filtered HCO3- [HCO3-
reabsorption], this occurs mainly in the PCT. The secreted H+ may react also
with ammonia (NH3) to form ammonium ion (NH4+), and with dibasic
phosphate to form monobasic phosphate [production of titrable acids (mainly
in DCT & CD)]. Note: the acid base balance is the balance between H+
secretion and HCO3- reabsorption by removing on of them from ECF and
passing it in urine. Factors affecting H+ secretion: 1- ↑ plasma CO2 [PCO2] as
in respiratory acidosis → ↑ H+ secretion. 2- ↑ K+ secretion → ↓ H+ secretion,
and vice versa. 3- Carbonic anhydrase inhibitors → ↓ H+ secretion. 4-
Aldosterone hormone → ↑ H+ secretion. 5- Marked ↑ in Na+ reabsorption by
renal tubules → ↑ H+ secretion → alkalosis. 6- ↑ Cl- reabsorption → ↓ HCO3-
reabsorption → ↓ H+ secretion → acidosis.

93. Characteristics of the urine
• Specific gravity: ranges between 1105 – 1025.
• Volume per 24 hrs: normally 1.5 – 2 liters. In acute renal failure may fall to
zero (anuria). It is decreased in chronic renal failure (oliguria).
• PH: normally about 6 [ranging “between” 4.5 – 8]. Note: Proteinuria is
defined as excretion of more than 150 mg of protein in urine / day.

94. Renal physiology
DR IBRAHIM ALGUBANI
PHYSIOLOGY DEPARTMENT

95. Renal diseases
Acute renal failure
It is sudden deterioration of kidney function. It can be caused by:
1- Acute damage to glomeruli [acute glomerulonephritis].
2- Acute damage to the tubules [acute tubular necrosis].
3- Acute obstruction of renal tubules [as in case of incompatible blood
transfusion → precipitation of hemoglobin in renal tubules]. Effects: In
moderate cases: rapid development of edema & hypertension. In sever cases:
edema, hypertension, azotemia, and acidosis, and the patient may die within
few days.

96. Chronic renal failure
It is a gradual deterioration of kidney function. It is caused by:
1- Chronic glomerulonephritis.
2- Inflammation of renal pelvis & parenchyma [pyelonephritis].
3- Destruction of nephrons [e.g. by vascular diseases].
4- Urinary tract obstruction [as in renal stones].
5- Congenital polycystic kidney.

97. Effects of CRF:
1- Water retention and edema.
2- Azotemia [↑ non protein nitrogen in the blood (mainly creatinine, urea, &
uric acid)].
3- Metabolic acidosis [due to failure of H+ secretion].
4- Hyperkalemia.

98. 5- Anemia.
6- Osteomalacia [weakness of bone due to ↓ serum Ca+].
7- Hypertension [due to Na+ & water retention and ↑ rennin production].
8- Uremic coma [due to acidosis, Hyperkalemia, & azotemia].

99. Nephrotic syndrome
This disorder is characterized by loss of large amount of plasma proteins into
urine [sever proteinuria] due to increased permeability of the glomerular
membrane.
Nephrogenic diabetes insipidus
It is excretion of large amount of diluted urine despite of normal ADH as a
result of unresponsiveness of renal tubules to ADH.
Renal tubular acidosis
It is a type of metabolic acidosis in which the tubules can’t secrete H+.

100. The urination [micturition]
• The urinary bladder is the site that stores the urine until it can be evacuated.
• It can accommodate urine with only slight increase in the intravesical
pressure until the bladder is nearly full. This is due to the plasticity of its
smooth muscles.
• Sensations from urinary bladder at different urine volumes are:
1- At urine volume 150 – 300 ml [sense to micturate].
2- 300 – 400 ml [sense of fullness of the bladder].
3- 400 – 600 ml [sense of discomfort].
4- 600 – 700 ml [pain sensation].
5- After 700 ml [break point (can’t suppress micturition)].

101. Micturition reflex
Stimulus: ↑ pressure in the bladder due to urine collection [in adult 300 ml of
urine can initiates the micturition reflex].
Receptor: stretch receptors in the wall of the bladder.
Afferent: afferent fibers in pelvic nerve.
Center: 2, 3, and 4 sacral segments of the spinal cord.
Efferent: efferent parasympathetic fibers in the pelvic nerve.
Response: contraction of the wall of the urinary bladder and relaxation of the
internal urethral sphincter → micturition.

102. Voluntary control of micturition: In the adult person, the cerebral cortex can
control voluntarily the micturition by descending pathways that may:
• Delay the micturition by:
1- Inhibition of the spinal micturition center.
2- Contraction of the external urethral sphincter.
• Initiate the micturition by:
1- Contraction of abdominal wall muscles → ↑ intravasical pressure.
2- Relaxation of the external urethral sphincter.
3- Stimulation of the spinal micturition center.

103. Abnormalities of micturition
1- Atonic bladder:
This condition occurs as a result of destruction of afferent fibers from the
bladder which will lead to loss of the reflex. In this case, the urine will collect
in the bladder till the intravesical pressure overcomes the tone of the urethral
sphincter → dripping of urine drop by drop. The continuous distension of the
bladder makes it thin walled & hypotonic.

104. 2- Hypertrophic bladder: This condition occurs as result of destruction of both
afferent and efferent fibers of the bladder. This will make the bladder
shrunken and hypertrophied. The exact mechanism of this is not known.
3- Automatic bladder: it is the loss of voluntary control of micturition that
occurs in cases of complete transection of the spinal cord above the sacral
region.

105. Acid – Base regulation
PH: it is the [– log H+ conc].
• Generally, the PH range is “between” [7 – 14]. The PH =7 is considered as
neutral. PH more than 7 is alkaline [less H+ conc] and PH less than 7 is acidic
[more H+ conc].
• PH of normal arterial plasma = 7.4 [slightly alkaline]. This plasma PH in
extreme acidosis = 7, and in sever alkalosis = 7.8. Beyond these levels [7 – 7.8]
any change in PH will be fatal.

106. Buffer: it is the substance that prevents marked changes in PH of solution
when acids or bases added. Most buffers consists of weak acids + its salt with
strong base [e.g. H2CO3+ & Na HCO3-]. The effectiveness of any buffer system
depends on: 1- The amount of the buffer presents [direct proportion]. 2- The
PK of the buffer [– log Ka (Ka = degree of ionization or strength of the acid)].
The buffer is most effective when its Pk equals the PH which it preserves.

107. Sources of H+ in our body
• CO2 formed by aerobic oxidation of food [CO2 + H2O ↔ H + + HCO3-]. Most
of the CO2 is excreted in the lung, and only small amount gives H+ which is
excreted by the kidney in the urine.
• The anaerobic breakdown of glucose [as in strenuous exercise] → lactic acid.
• And there are many other sources.

108. Mechanisms of acid base balance
I- Chemical buffers
a- Bicarbonate – carbonic acid system: It is composed of H2CO3 (CO2) and Na
HCO3. Despite this system is not powerful one, it is more important than all
the others in the body. The concentration of the 2 components can be
regulated by the lungs [H2CO3 (CO2)] and by kidneys [HCO3-].

109. b- Phosphate buffer system: It is composed of sodium monobasic phosphate
[NaH2PO4] and sodium dibasic phosphate [Na2PO4]. It is a weak buffer. On
the other hand, it is especially important in the tubular fluid of kidney and in
the intracellular fluid for 2 reasons: 1- The high concentration of PO4 in these 2
areas. 2- The PK of phosphate buffer is close to the PH of these 2 fluids
[tubular & ICF].

110. c- Protein buffer system: In normal plasma PH the proteins act as weak acids.
They are the strongest buffers in the body because of:
1- Their high concentration. 2- Their PK is near 7.4 [= plasma PH].
This system includes:
1- Plasma proteins: [7 gm/ 100 cc]. They are stronger buffers than HCO3-.
2- Hemoglobin: it is the strongest blood buffer system. Its power is 6 times as
that of plasma proteins. It plays most important role in buffering CO2.
3- Tissue proteins: the strongest chemical buffer in the body due to their huge
amount.

111. II- Respiratory regulation
The respiratory system controls PH of the body bycontrolling the CO2 tension
[PCO2] of the blood. The ↑ CO2 → ↓ PH and vice versa.
• In case of acidosis: the respiratory center is stimulated → CO2 washout →↓
PCO2 →↑PH back to normal.
• In case of alkalosis: the respiratory center is depressed → CO2 retention →
↑ PCO2 →↓ PH back to normal.

112. The buffering power of the respiratory system is2 times as powerful as all
chemical buffers combined.
It is characterized by that it is:
1- Rapid: starts within minutes [3 – 12 minutes].
2- Incomplete: corrects the PH changes by 50 – 75 % only.

113. III- Renal regulation
The kidneys regulate the PH by controlling the plasma HCO3– concentration
and the amount of H+ secreted.
• In case of acidosis: there is ↓ plasma HCO3– & ↑ in H+ secretion. This will
lead to excretion of acidic urine by:
1- Reabsorption of all the filtered HCO3–.
2- Excretion of more ammonia & titrable acids [H+ sources]. This will lead to
excretion of acidic urine [lowest urine PH can be reached = 4.5].

114. • In case of alkalosis: the kidney will excrete less acidic urine [alkaline] urine
with maximum PH = 8 through:
1- ↓ Reabsorption of filtered HCO3-.
2- ↓ Excretion of ammonia and titrable acids.
The renal control of PH is:
1- Slow mechanism [takes hours or days].
2- More complete than respiratory correction.

115. Clinical abnormalities of acid base balance
Acidosis: [↓ PH below 7.4 (or ↑ H+ conc)]. It could be respiratory or
metabolic.
Alkalosis: [↑PH above 7.4 (or ↓ H+ conc)]. It also could be respiratory or
metabolic.
To diagnose any case of acid base disturbance we have to measure:
1- PH of the blood [to know is it acidosis or alkalosis].
2- PCO2 & plasma HCO3- [to know is it respiratory or metabolic]. [See the
tables in the next 2 pages for comparison between respiratory and metabolic
acidosis & alkalosis].