Renal Physiology

Content

 Overveiw of kidney anatomy

 Renal Function
 Glomerular Filtration
 Autoregulation
 Proximal convoluted tubule
 Loop of Henle
 Distal convoluted tubules
 The collecting ducts

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 Renal Physiology

‫المحاضرة االولى‬
Renal physiology (kidney)
 What is the function of the kidneys? where are the kidneys located?
 The abdomen is divide into several regions:
-right and left hypochondriac.
-epigastric & umbilical regions
-right and left lateral regions
-right and left inguinal regions.
-hypogastric.

in addition to
1. umbilical region between right and left iliac Fossa. ( From anterior)
2. Flank region between anterior and posterior axillary lines. (From the sides and backs)
3. loin region between posterior axillary line and vertebrae. (From Posterior)
4. Groin region Connection areas between the thigh and trunk.
The boundaries of these areas.
From Superior 12 rib
From inferior iliac crest
 The kidneys are located in the loin region.
NOTE:
The left kidney is higher than the right kidney.
one of the Functions of the kidneys is to excrete waste. and contribute to maintaining balance.
How are the kidneys involved in maintaining homeostasis?
homeostatic of the kidney.
1. Fluid balance electrolyte balance
2. acid base balance.
3. regulating blood pressure.
4. erythepoietin hormone
5. Renin release
what are the Factors that stimulate renin release?
hyponatremia
hypotension..
hypovolemia.

•Renin stimulation is related to blood pressure regulation.

There is a relationship between the release of erythropoietin and Formation and production of

blood cells.
What are the main factor that stimulate the release of erythropoietin?

 hypoxia.

- The kidneys are related to homeostasis of vitamin D and homeostasis of calcium.

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 Renal Physiology

- the Common Cause of hypercalcemia excess parathyroid hormone.

an increase in calcium levels in the blood can affect kidney Function
when the calcium level is high, more than  11.5.

Calcium precipitation Occurs in tissues. (Calcinosis or kidney stones)

- it causes several problems in the various organs, such as the Heart and the brain
Also, decrease excretion of calcium From the kidneys. Causes hypercalcemia due to it return
to the blood.
How are the kidneys involved in metabolism?
Gluconeogenesis, only in starvation
- The process of producing glucose From non-Sugar Sources.
How are the kidneys involved In Maintaining the homeostasis trigon?
homeostasis trigon is
1.acid base balance...
2. Fluid balance.
3. electrolyte balance
 In renal system there are three important things to regulate pH
 excretion of hydrogen sons.
 Bicarbonate reabsorption
 Degeneration of Bicarbonate
what is the main thing that the kidneys do to maintain normal physiological functions?
1. Filtration
2. Secretion
3. Reabsorption
4. excretion.
 what is the difference between Secretion and excretion:
 Secretion is from the blood into the renal tubule.
 excretion From renal tube to ureter to the outside like urine.
- If it moves from the tubule to the capillaries it will be reabsorbed

Note:

The opposite of Secretion is reabsorption.

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‫المحاضرة الثانية‬
 Renal system

⁃ Main function are:

1-Secretory 2- Excretion 3- Regulate Blood Pressure

4-Electrolyte balance 5- Acid-Base balance.

6-Gluconeogenesis —> just in Starvation.

 To give these functions of renal system we have certain process take over in the
renal physiology.
 Firstly: filtration
 Secondly: Secretion or reabsorption
 Lastly: Excretion. (voiding) ‫البول إخراج‬
 Regarding filtration:
 around 20% of output will be filtered through glomerular capillaries to Bowman's
capsule.
 ⁃ Bowman's capsule + glomerulus = Renal corpuscle ( Malpighian corpuscle)
 Renal corpuscle —> one part of nephron

⁃ In kidney there are Renal corpuscles after that:

Pyramids renal papillae minor calyx major calyx renal pelvis.

In the hilum of kidney major calyces diverge to form renal pelvis.
- Pyramids and adjusted cortical zone takes—> one segment called lobes.
_ each lobes contain renal pyramids surrounding by interlober arteries connect with
each other to form segmental artery then renal artery .

⁃ The Hilum is order from anterior to posterior (vein - artery - ureter)

-There is one ureter in Right side and one in Left side , both go towards urinary bladder.
 Renal ➡️segmental ➡️lobar ➡️interlobar➡️ arcuate➡️ interlobular(radial) ➡️afferent ➡️ glomerulus
➡️efferent arterioles to venous circulation.
- The radial cortical arteries give afferent arterioles.
-From this area to the medulla there are two types of nephrons. ( Cortical (80-85)-
juxtamedullary(15-20) )
 - Nephron is the functional unit of the renal system:
 types of nephrons:
 1- Cortical nephron
 20- 15 % Juxtamedullary nephron in the cortex extend to medulla region.

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o ⁃ Renal artery interlober arteries arcuate arteries radial

cortical arteries —> Afferent arterioles.
o ⁃ Afferent arterioles enter firstly to corpuscle.
o ★ leave the corpuscle as efferent arterioles.
o ⁃ The only system in the body which has input is artery and out put also artery.

⁃ Do you know the reason?

•to form high pressure capillaries tuft ( ultrafiltration)

Because there are smooth muscle on arteries make vasoconstriction and vasodilation,
when vasodilation or vasoconstriction happen in input (arterioles) make change in net
filtration pressure also vasoconstriction or vasodilation occurs in output (efferent)
because it is arteriole (smooth muscle).

 ⁃ In both we have the tow actions (vasoconstriction and vasodilation).

 Any change in them (input, output) will cause change in net filtration pressure which
will change filtration and filtration is the main function means Glomerular Filtration
Rate GFR.
 GFR = normally 20% from renal plasma flow will filtered in Bowman's capsules.
capsules:‫ هناك‬cortex ‫ المنطقة األساسية في الـ‬
 ⁃ (Bowman's capsule + Glomerulus) .
 Glomerulus is structure of (afferent arterioles, glomerular capillaries and efferent
arterioles)
 ⁃ From the head of Bowman's capsule the arteriole enters as afferent and exits as
efferent arteriole and reach to proximal convoluted tubule.

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 ⁃ Juxtaglomerular cells in afferent arterioles Juxta means —> ‫مجاور‬.

 glomerular —> capillaries.
 ⁃ Parietal cells : squamous flat epithelial cells of Bowman's capsule.
 ⁃ visceral layer —> Podocytes.
 ⁃ Podocyte has feet like projection in cytoplasm.
 ⁃ Podocyte is the 4th layer in the filtration layer membrane.
 ⁃ Filtration membrane like respiratory membrane , between this capillary and
between visceral layer of Bowmen’s capsule, parietal layer found in parietal area.
filtration.‫ وهذه الفتحات هي التي تعمل‬visceral ‫ ⁃هناك فتحات في الـ‬
 ⁃ Parietal layer—> squamous flat cells.
.‫ الموجب‬H+ ‫ ⁃البروتين سالب ينقص الحمضي لـ‬
 ⁃ Extern-a lamina and internal lamina are negative charge.
:‫ إ ًذا شروط المرور هي‬
.‫ نانومتر‬١٠٠ ‫ ⁃قطر أقل من‬
.‫ ⁃شحنة موجبة‬
 ⁃ Negative charge will pass with condition as (chloride, HCO3-, PO4- ) they dissolve
and small.
 ⁃ Fourth layer is Podocyte, between Podocyte there are Filtration slits.
 slits mean ‫خزق‬.
 ⁃ Bowman's capsule ‫ تتبع‬Podocyte ‫ال‬
 Slits Filtrate allow for particles which less than 9 nm.
 20%of the (Blood or plasma) Come from glomerulus (capillary) will goes through the
glomerular membrane.

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 which consist of:-

1- Endothelial cell (fenestrated Capillary) Allow the particle from 50-100 nm pass through.
2- Basement membrane formed of 3 layers from inside out ( lamina rara interna - lamina
densa - lamina rara externa) .
3-veceral layer of Bowman Capsule Allow particle less then 25 nm
4-pondocyte Between them are structural protein called nephrin which Allow the particle
less then 7-9 nm to passing.

 To achieve filtration:
We should Have these factors:
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1 -pressure gradient across filtration membrane; must be different:

-Hydrostatic pressure; control movement of Blood thorough the glomerulus to Bowman’s
capsule.
-Oncotic pressure: -against the hydrostatic pressure decrease diffusion of the Blood
to Bowman Capsule keep the blood Inside Capillary (Created By Negative charge of PLASMA
Protein).
-Hydrostatic pressure inside glomerulus works against the Hydrostatic pressure inside
Bowman Capsule
↑Hydrostatic pressure inside Bowman inside Bowman Capsule Will decrease filtration, But
high Oncotic pressure Inside Bowman Capsule ↑fistulation, and verse versa (But there is
no oncotic pressure inside Bowman Capsule That means:
Hydrostatic pressure is ‫دافعة قوة‬
diffusion of Solvent ‫ولها عالقة بـــــــــ‬
Solute from high cone —> Low Concentration

Oncotic pressure (- Charge); ‫قوة ماصة‬

Osmosis: movement of water from Low Concentration to high Concentration of solution.
•Glomerular hydrostatic pressure (PGC)=60 mmHg

 Glomerular oncotic pressure (plasma) (πGC)=32mmgHg

 Bowman’s capsule hydrostatic pressure = 15 mm Hg oncotic (resist)
 Bowman’s capsule oncotic pressure=0
• PGC against PBS 60mming -15 mmHg =45mmHg
• 𝜋GC against 𝜋BS 32mmHg -0 = 32mmHg

• 45-32 = 13 this is Net glomerular filtration pressure.

NFP: -Should Be positive
if NFP=0 Renal failure
2 factors influence NFP: -
1) Surface area: The surface area of the glomerular capillaries in the kidneys is indeed
proportional to the net filtration pressure (NFP). A larger surface area allows for more filtration
to occur, resulting in an increased NFP. In the case of hypertension (high blood pressure)
associated with diabetes mellitus (DM), there can be a decrease in the surface area available for
filtration.

2) Permeability: The permeability of the glomerular filtration barrier plays a role in NFP. In
Nephrotic syndrome, there is an abnormal increase in the permeability of the glomerular

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capillaries. This increased permeability allows proteins, including albumin, to pass through the
filtration barrier and be excreted in the urine.

 Calculation of GFR:
GFR (glomerular filtration rate) is a measure of how well the kidneys are functioning in
filtering waste and fluid from the blood. There are different methods to calculate GFR:

1. Chronic kidney disease (CKD) epidemiology: This method takes into account factors
such as age, race, and gender to estimate GFR. These demographic factors can influence
kidney function and provide an estimation of GFR in the general population.

2. MDRD equation (Modification of Diet in Renal Disease): This equation is commonly

used to estimate GFR. It includes constants that are used to adjust the estimation based
on factors such as age, sex, and creatinine levels. Creatinine is a waste product that is
filtered by the kidneys, and its level in the blood is used as an indicator of kidney
function. However, the MDRD equation may not provide accurate results in certain
populations, including individuals with normal creatinine levels, Black Americans, older
patients, or pediatric patients.

Direct methods to assess GFR:

In cases where the MDRD equation may not be accurate, direct methods can be used to
assess GFR. Two examples of direct methods are:

1. Cysteine: This method involves the administration of cysteine, a substance that is

filtered by the kidneys. By measuring the amount of cysteine in the blood or urine, the
GFR can be directly assessed. However, this method may not be suitable for individuals
with progressive renal impairment.

2. Atomic scanning: This method utilizes atomic scanning techniques to directly measure
the filtration rate of the kidneys. It provides an accurate assessment of GFR but may not
be practical for routine clinical use.

But all these methods may not accurately reflect the true GFR.

progressive renal disease which means that the kidneys gradually lose their ability to
filter waste and fluid from the blood , if a patient's creatinine level is initially 0.8 mg/dl
and then increases to 1.5 mg/dl on the second day and 3 mg/dl on the third day, it
indicates a rapid progression of renal disease. The rapid increase in creatinine levels
suggests a decline in kidney function over a short period of time. This would typically
warrant immediate medical attention and intervention, as it indicates a significant
deterioration in kidney function.

 When we want to know filtration rate we depend on the creatinine, BUN and urine
Any output.

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 patient has adequate urine output (according to age and weight 0.5 -1m/kg/hr )this
means when the patient enters into intensive care unit we need urine according to
his weight ,means when patient weight is 70 kg I need 35 to 70cc every hour after
that we multiply it with 24.

 which electrolyte filtered in bowman’s capsule :-

o Na , CL , K , Mg , Ca , HCo3 , urine , Po , lactate , glucose, A.A , FA , some

hemoglobin , small protein like hemoglobin and insulin.
And hydrostatic pressure which push them to Bowman capsule from high to
low mean from kidney to ureter and other organ.
 Main rule :- when filtration is 20% - 19% of it will be reabsorbed and reabsorption
will occur at Proximal convoluted tubule in Renal collection duct .
 Juxtaglomerular apparatus. →Afferent arterioles go to Bowman capsule) in the
mouth of Juxtaglomerular we have cells and mesangial cell and granular cell around
arterioles(
- In mouth of Juxtaglomerular macula densa of distal convoluted tubule will be
apposed to Juxtaglomerular apparatus.
- Macula densa is chemoreceptors while Juxtaglomerular cell which has
relation with arterioles is baroreceptors
Mesangial cell has more actin do contraction to help in afferent contraction.
- Mesangial cells have the action of contraction to help in afferent contraction.
 When get changes by local blood pressure, hypovolemia, or hyponatremia these
has relation to changes in many things one of them renin , ADH , ACTH , CRH
Epinephrine (sympathetic activity).

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-Renin in Juxtaglomerular apparatus will be sensitive to hypotension ,hyponatremia,

hypovolemia by it self release renin and renin will be released in the blood stream inside the
arteriole and go to efferent arterioles to peritubular capillaries to radiolocortical venules
arcuate vein to interloper vein to renal vein.
- Renin. → Activating enzyme will convert Angiotensinogen to
Angiotensin1.
- Angiotensin1.→Proenzyme will be going to the lung and in the lung present
Angiotensin converting enzyme which convert Angiotensin1 to Angiotensin2 .
- Angiotensin2 most important in person has hypertension because it's doing
several thing like
1. Stimulation CRH.
2. Activation of steroids convert it to aldosterone in adrenal gland .
3. Vasocontraction.
4. ADH secretion.
5. Efferent arteriole contraction.

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 In vasocontraction. → increased Resistance and ↓ flow so filtration

decreased.

 In vasodilation .in afferent arteriole.↓ Resistance and ↑ flow and ↑filtration.

stance to propel heart pressure. Proximal part ‫ اللي هي‬but distally will effected.

 For each corpuscle has afferent and efferent arterioles.

 ↑ vasoconstriction in the Efferent arterioles → ↑ hydrostatic pressure in the
glomerulus lead to high GFR
Efferent spasm and Angiotensin II secretion will motivate the hypothalamus to stimulate
secretion of:

 ADH-post

 CRH- has relation with ACTH. ant

ADH → posterior hypo → has a relation with the fibers nerve.

ACTH → Ant. hypothalamus → has a relation with blood vessels.
↑ Osmolality in the blood all the body part will effected (↑ extracellular compartment but
intracellular compartment → no change)

 Then normal Osmolarity is 300 mosm

Means ↑ mosm Osmolarity increase

↓Mosm Osmolarity decrease
Osmolarity ↑: reference for extracellular compartment

The normal Osmolarity = 300 mosm out and inside the cell
The increase in peripheral tissue occurs in interstitial and vascular but intracellular no
change.
If the Osmolarity will be 350 mosm all the cell will affected and →now the hypothalamus
area and the ADH area secretion released.
Start: the fibers will be affected by ↑ Osmolarity because its sensitive.
Osmosis of water. The water will transport from cell (less solutes ) to extracellular (high
solutes)
In the neurons of the posterior pituitary gland, specifically the supraoptic neurons, when
they become stimulated, they cause shrinkage in the distal parts. When this shrinkage
occurs, it triggers the secretion of antidiuretic hormone (ADH), which leads to the
reabsorption of water from the renal tubules.

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 The ADH action:

1. Reabsorption of water
2. Vasoconstriction
Which causes reabsorption of water to preserve

And increase blood pressure so that increase the volume.

The normal rule: Na goes, water follows:
When there is a difference in the concentration of solutes (such as ions and dissolved
molecules) between the solution inside a cell and the solution outside the cell, there is an
osmotic gradient between the two sides. Cells always strive to achieve equilibrium and maintain
concentration stability. Therefore, water moves from an area of lower solute concentration to
an area of higher solute concentration in an attempt to equalize this difference.

If there is a difference in osmolarity between the intracellular solution and the extracellular
solution, the cell is affected by the flow of water. When the osmolarity of the intracellular
solution is higher than that of the extracellular solution, water will flow from the extracellular
solution into the intracellular solution, causing the cell to swell. Conversely, if the osmolarity of
the intracellular solution is lower than that of the extracellular solution, water will flow from the
intracellular solution to the extracellular solution, causing the cell to shrink.

↑ Osmo → ADH secretion which

1. increase volume

2. increase blood pressure

But cause ↓ Na (hyponatremia) because osmosis happen from low concentration to high
concentration
The response that happens as a receptor of renin appear as a hyponatremia and ' the blood
pressure cause stimulation of renin from Juxta cells → renin → blood → conversion of
angiotensinogen that is available as a protein in the blood → angiotensin I → heart → lung
→ alveolar cells → angiotensin II → ↑ vasoconstriction → ↑ blood pressure in systemic
circulation also to the efferent arterioles to cause vasoconstriction more pressure in
Capillaries and afferent arterioles so more GFR
Adrenal cortex: in the beginning, release of CRH- stimulates the anterior pituitary to release
ACTH

Steroids stimulates → Aldosterone

Renin secretion stimulates→ angiotensinogen
And ADH → from hypothalamus
And stimulation of adrenal of Aldosterone secretion
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The minor: from up to down

(Means from hypothalamus to release Aldosterone)
The major: from Angiotensin II to adrenal to release Aldosterone
The main idea:
 The ADH reabsorbs water and leave Na.
 The Aldosterone makes an action on Na - K occur in the distal convoluted tubules.

Na reabsorption
K excretion
1) Hypotension

 Angiotensin 2 increased as a response.

2) Hyponatremia

 Aldosterone increased as a response.

3) Hypovolemia

 ADH increased as a response.

Obligatory means any Na reabsorbed water must follow.

Except in pathological conditions:

1. Syndrome of Inappropriate ADH secretion : high secretion of ADH

2. Diabetes insipidus: no ADH or no receptor for ADH .
When no ADH → polyuria → polydipsia → hypernatremia: ↑ Osmolarity → death.
The drug is vasopressin as ADH hormone
The normal urine in a day 1680 ml per day, but in diabetes insipidus patient excretes 15
liters. And that causes:

 Severe dehydration
 Severe hypovolemia.
 High Osmolarity.
 Polyuria - decrease weight.
.‫يجب علينا مراقبة المريض وقياس كمية اإلخراج والزم نعطيه فاسوبرسين ألنه إذا تركنا المريض يموت‬
The opposite: in syndrome of appropriate ADH , ADH is high or inappropriate secretion.

But the normal stimulation for ADH as:

1. Thirst sensation

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2. Hypotension
3. Hypovolemia
In the syndrome of inappropriate ADH:
And because ADH cause water retention without Na+ reabsorption Subsequently, Increase
reabsorption of water causes hypervolemia and hyponatremia → water toxicity → 1-
Pulmonary edema
2-Lower limb edema

3-Cerebral edema
4-Sacral edema
5-Buffness of the face

 Edema caused due to:

1. ↑ Hydrostatic pressure
2. ↓oncotic pressure liver - renal - malnutrition - neuropathy
3. Leaking capillaries → capillaries problem
4. Venous obstruction → causes ↑ hydrostatic pressure
5. Lymphatic obstruction → Non-inflammatory lymphatic obstruction

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‫المحاضرة الثالثة‬
 Autoregulation maintain the glomerular filtration rate (GFR), maintain the blood
flow remain normal even when BP or BP within normal limits ( 70- 200mmHg).
 According to these changes in BP should occur modifications to nephron and its blood supply
to reflect changes in renal blood flow.
 We need constant blood flow to prevent:
 Ischemia
 GFR
 Tubular necrosis
 Kidney failure
 So all the time accommodation to these systems to have normal GFR
normal kidney function.

Extrinsic outside control

 Autoregulation
Intrinsic within control

 Intrinsic control has two factors:

1) Myogenic

If BP stretch in afferent arterioles

Influx Na which initiate Ca influx and release it from the sarcoplasmic reticulum
actin-myosin activity contraction smooth muscles .
If BP no stretch no Na influx no Ca release no contraction→→
dilation (relaxation) of smooth muscle.
Both of them keep normal RBF most important keep constant GFR ( Kidney Function).
2) Tubuloglomerular feedback reflex

If BP hydrostatic pressure GFR Nacl flow in MD . If

this occur lead to inhibit renin release and stimulate secretion of adenosine and other
constrictors of Afferent arterioles to ↓ hydrostatic pressure and ↓ GFR → ↓ tubular flow → ↓ Nacl
reaching MD.
In detail as below:
Some of Nacl is reabsorbed in proximal tubule and the remain continue to distal tubule transport to
the cells by Nacl receptors,

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 Renal Physiology

Cl get diffused to the blood ( apical-basal transport).

Na trigger to release ATP then transported to blood as adenosine
Adenosine bind to the receptors in mesangial cells stimulated SR to release Ca connect to
smooth muscles is afferent arterioles and cause contractions  BF GFR
If BP is low  low hydrostatic pressure  GFR  Nacl in macula densa break down special
chemical into No2 and PGE2  cause relaxation of smooth muscles and dilation  ↑↑ GFR by two
mechanism
1- through vasodilation of Afferent Arterioles by PGE2 and other dilators.
2- increase the secretion of renin from juxtaglomerular cells of JGA lead to increase Angiotensin II
this act by contraction of Efferent Arterioles lead to ↑↑ GFR .
#Mind_Strom : Why do that when we eat a meal rich in meat increase the renin in blood even GFR
remaining normal? Answer at the end of the lecture

 Extrinsic control has two factors:

1) Sympathetic activity response in change in BP

Baroreceptors sinuses aortic and common carotid artery sinuses response in BP (main action
in hypotension not hypertension)
 purification common carotid artery sinuses through glassophryngeal nerve

and aortic sinuses through vagus nerve.

 Glassophryngeal nerve + vagus nerve higher center medulla
sympathetic nerve adrenaline and noradrenaline, these constrict the afferent
arterioles → decrease blood flow to kidney keep blood in emergency for vital organs as brain
& heart.
 Sympathetic receptors:
o Alpha 1 : mainly in blood vessels especially in afferent arterioles
o Beta 1 : in heart and JG cells also in extra medullary mesangial cells.
 Sympathetic response by epinephrine and norepinephrine at BP:
o Alpha 1: in afferent arterioles, vasoconstriction blood resistance BP
GFR
o Beta 1: heart rate stroke volume ➡️ increases COP ➡️SPR
2) Renin – angiotensin – aldosterone system (ADH system)

BP (either hypotension, hyponatremia or hypovolemia)response in JG cells stimulated

release Renin in blood and convert angiotensinogen (release from liver) into angiotensin I
(by converting enzyme from lung) into angiotensin II
 Angiotensin II related to function in autoregulation, activate:

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1) ↑↑ secretion of Aldosterone work at DCT reabsorb Na, H2O (indirectly), secretin, H and K
ions
2) CRH :
- thirst
- Aldosterone
- ADH secretion
3) ADH reabsorb of water from lumen to cells ( Aquaporin II then to plasma by Aquaporin
III&IV).
4) Vasoconstriction in efferent arterioles of Bowman’s capsule to increase GFR.
 Aldosterone act on distal tubule to absorb of Na with water and secret H and k.
 Juxtaglomerular cells stimulated by hypotension, hypovolemia and hyponatremia and one of
them stimulate sympathetic nerves.
 ADH has not to do with interstitial to blood vessels, interstitial has to do with osmosis
gradient.
 ADH has to do with aquaporin 2 in the apical or luminal area.
 The main idea is: From lumen to cells .

And make initiation for aquaporin 3,4 which found in basolateral always found, independent to
ADH.

 ADH has indirect relation with GFR

 Main stimulator of ADH is: decrease volume, Decrease BP
 ANP (Atrial Natriuretic Peptide) on the heart

If stretch happened to it (heart) due to increase volume or BP in atrium will lead to:
o Release ANP in atrium, or in ventricle called ( BNP)
o Release BNP (Brain Natriuretic Peptide or B-type Natriuretic Peptide) from ventricle.
 ANP and BNP their action is opposite to Renin and aldosterone mechanisms
 Renin & Angiotensin II  vasoconstriction of efferent arterioles  increase influence
 BNP and ANP  vasodilation to afferent and efferent arterioles also work as naturiasis and
daiurasis excretion of Na and H2O to urine ,so decrease volume, decrease intravascular
volume
 Which causes stimulation of ADH causes inhibition of ANP & BNP
 Renin: its action by converts angiotensinogen to angiotensin I
 Angiotensin II: its action on proximal tubule increase reabsorption of Na by activation Na-K
ATPase pump .
 Aldosterone acts on distal tubule, collecting duct.
 ANP & BNP are used as drugs to decrease intravascular volume.
 Aldosterone has the opposite action of BNP & ANP

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Function of ANP and BNP:

1- decrease the reabsorption of Na in the medullary collecting duct

2- vasodilation of afferent and efferent arterioles

3- decrease the release of renin.

Aldosterone: increases Na leading to increase the volume and excretion of K

ANP: dilating afferent arterioles and the efferent arterioles dilations of both but more dilations of
Afferent arterioles.
ANP & BNP: excretion of Na in the urine follow by water decrease intravascular volume.

 Autoregulation: constant renal blood flow

 Renal blood flow has to do with GFR most important GFR .
 Renal clearance: can be determined by many factors the best of them in which no
absorption or excretion is occurring.
 Assessment of renal function general depend on PUN & creatinine
 Creatinine is one of the end product and excrete to urine
 Urea is also one of the renal function tests but because urea can increase if you eat meat or
decrease in liver disease not use nowadays.
 The most accurate is creatinine (why) because urea can increase by other than
renal reasons ,like dehydration, starvation and increase in protein load and some infection
cause increase in urine concentration even hheart disease ncrease urea concentration.
 Also creatinine isn't unique and adequate because know increase creatinine in blood until
more than 50% of the kidney has been destroyed.
 Also we can use Inulin but because it is exogenous use IV not usually used in clinical practice.
 Nowadays they start using (Cysteine C ) the best
 If urea and creatinine are normal renal function will be normal.
 Urine output is standard for GFR
 Normal function of kidneys :
- Filteration
- Reabsorption
- Secretion
- Excretion
 Formation of urine starts by:
- Filtration
- Reabsorption
- Secretion ( filtration – reabsorption + secretion = excretion).
- Excretion
 Filtration:

20
 Renal Physiology

o 20% of CO goes through renal arteries about 1.2 L

o 80% of CO goes to other tissues
o Out of this 20% ( 1200 ml) 40 percent ( 450 )is Blood element and 60% ( 650) is plasma.
o Out of this 60% plasma only 20% is filtrated about 120ml .
 The 20% which is filtered: 19 will be reabsorbed and 1 will go to renal tubules
 In renal region of nephron can be classify by glomerulus and Bowman’s capsule
proximal convoluted tubules descending segment (thick and thin)
 Kidneys Cortex & medulla
 In medulla Medulla divide nephron into two parts, outer (proximal & distal
convoluted tubules) inner ( loop of Henle).
 Two types of nephrons:
 85% cortical nephrons
 15% juxtaglomerular nephrons
 Vasa recta has three characteristics:
1) Slow blood flow
2) Straight distribution
3) Between renal tubules
4) Contribute to medullary Osmolarity.
 Vasa recta and medullary nephrons have important relationship give
corticomedullary gradient that is important point in renal system to maintain
corticomedullary gradient.
 Gradient : in cellular and paracellular transportation by tight or gap junctions to transport
throw cells from extravascular to intravascular or the opposite has to do with two things:
1) Trans-cellular or paracellular
2) Active or passive
 Passive is two kinds:
1) Passive diffusion
2) Passive osmosis

Osmosis Oncotic

Is the force that drives the Is the force exerted by proteins

movement of water molecules Mainly (albumin)
from a region of low solute concentration toinathe draws water into the area of high
high solute concentration concentration of proteins.

 Movement is to water or to solute

 Water moves only with osmosis and should have osmotic pressure
21
 Renal Physiology

 Osmotic gradient has to do with solutes

 Osmotic pressure or osmolality of blood =

V × Conc. Of (Na + K + glucose/18 + blood urea nitrogen/2.5) .

concentration gradients ‫المعيار النتقال الماء من او الى داخل الخليه هو االختالف في‬

Diffusion has to do with two things:

1) Permeable membrane
2) Dissolve solutes, from high concentration to low concentration
 Osmolality is formed by Na, k, urea or glucose
 Osmosis ‫خاصية ماصة‬ ‫تعني سحب الماء من الوسط ذو التركيز‬
‫المنخفض إلى الوسط ذو التركيز العالي وعند‬
. ‫تساوي اسموزية الطرفين تتوقف الحركة‬
Semi membrane to make equilibrium between the
two sides.

 The normality is: intravascular compartment and extracellular compartment

= 300 mosmol
Means movement of water inside = movement outside , that Means balance.
 What's the differences between osmosis and colloid Osmotic pressure ( oncotic
pressure)?
 Oncotic pressure: it’s the Osmotic pressure created by protein in plasma (mainly
albumin).
 (Osmosis) the osmotic gradient (pressure): that control the movement of water pull
the water toward high Osmotic pressure which provide mainly by Sodium, chloride
,urea ,and glucose.
 The difference is in which cause this Osmotic gradient.
 calculation the colloid osmotic pressure by the following:
Equation = 0.93 × conc. of albumin (3.5 g)
= 0.93 × 35 ml
= 32 mosmol / L
 Electrical chemical gradient: in every cell in human body there is transporter protein
called Na,K ATPase pump ,this pump transport 3 Na outside the cell with 2 K to
inside the cell.
 This transport against conc. gradient . this transport create decrease cation
inside the cell make chemical gradient has a role in the resting membrane
potential.
 There are 3 Na outflux and 2 K influx that will create negative charge inside
the cell. Also because the cells have K+ leaking channel make K goes out
regarding their concentration inside and outside the cells. both of these
mechanisms are responsible for RMP = - 90.
22
 Renal Physiology

 Note / all the cells in the body has RMP , but not all of them has membrane
action potential.
 In the renal tubules, the Na to be moved from the lumen to the cell, it must
have two force:
1) Electrical force: Na has positive charge, and the luminal cell surface
has negative charge (due to Na,K ATPase in the basolateral
membrane) ,so the Na will move from lumen to the cell
2) Chemical force: the lumen has a lot of Na more than cells (due to Na,
K ATPase) ,so Na will move to the cell.
 Note:
Na reabsorption occur by primary active transport (due to Na, K ATPase in the
basolateral membrane). In luminal membrane the Na transport into the cells by
facilitated diffusion.
In this case Na will go to the cell and take with it many things: glucose, amino acids,
phosphate ,Chloride, lactate and so for .
This process is called Na dependent process as a response to Na, K ATPase pump.
o Na , cl , H2O reabsorbed in PCT 65% called ( obligatory reabsorption) some
says Cl is little less about 55-60%
o H2O absorption in the PCT by protein called Aquaporin I , it works due to
osmosis between the lumen and the cell also from cells into ECF also maybe
by paracellular route.
o H2O reabsorbed in DCT or CT by protein called Aquaporin II( luminal) ,it
works by ADH ( V2 receptor)  second messenger  G stimulatory pathway
or G inhibitory pathway.
o In the basolateral walls by independent on ADH ( Aquaporin III,IV).
 Role of PCT in acid base balance by three steps:
1) Secretion of H by secondary active mechanism called counter transport ( H+;Na
counter transports) help in reabsorption of HCO3.
2) Regeneration of HCO- : H secreted accompanied with HCO3 in the lumen under
influence of Carbonic anhydrase { acetazolamide diuretic} to form H2CO3 as
follow:
 H+ HCO3 C.A H2CO3
 H2CO3 disassociated to the H2O and CO2 - as follow:
H2CO3 H2O+ CO2
Co2 diffusion into the cells inside the cell the opposite occurs to make HCO3
secreted by special channels to ECF and H through luminal membrane by
H,Na antiport .
3) Reabsorption of HCO- by secondary active mechanism by Na

2) In DCT there are two types of cells:

 Principle cells: these cells reabsorbed H2O and Na while secreting K .
 Intercalated cells: they are two types:

23
 Renal Physiology

o Cells called A intercalated cells, those work during acidosis ( A with A) ,

they work like cells in the PCT not exactly the same in channels
o Cells called B intercalated cells, they work during alkalosis (basic), they
work opposite to the A intercalated cells.

So we have:

 Chemical gradient ( concentration )

 Electrical gradient (for Na )

1- Reabsorption of HCO3 by secondary active mechanism and Na is involved (but

indirectly) as follow:
 H excreted in the lumen as follow
H + HCO3 H2CO3
H2CO3 CO2 + H2O

Enter to inside the cell

CO2 (inside the cell) + H2O H2CO3

H2CO3 H + HCO3
HCO3 reabsorbed (regeneration)
H secretion (excretion)

And this is the importance of PCT in the acidosis

3) Note:
 The acidosis compensation of proximal convoluted tubules by:
A. Reabsorption of HCO3
B. regeneration of HCO3
C. excretion of H
acting as intercalated A cells
 The best solution for pollution is (dilution)
In case of acidosis increase CO2
In case of alkalosis decrease CO2

4) In the distal convoluted tubules occur:

1) Regeneration of HCO3
2) excretion of H
Or
o reabsorption of H
o excretion of HCO3

24
 Renal Physiology

o
5) Note:
 In the decrease in Cl the patient is given normal saline
 In case of diarrhea (Ca-K) the patient is given ringer lactate
 In case of vomiting (Cl) the patient is given normal saline
 In case of polyuria the patient is given glucose 5% or Dextrose 5%
 The body has more affinity to acidosis than alkalosis → cause it continue
generating H inside the cells.
 The reabsorption of HCO3 has with Na dependent (in PCT) also in thick
part of loops of Henle the same manner. While in late DCT and CD is Cl
dependent.

e.g., in the GIT when HCO3 enter the cell , the Cl must come out of the cell ,
But in the kidney it depends on the Na also in DCT and CD as in GIT occur ( HCO3 - Cl
counter-transport).
6) The reabsorption of HCO3 in
1) PCT is Na dependent
2) DCT is cl dependent
#Answer of mind storm → because when we eat meat there's a lot of protein digestion and
a lot of amino acid absorption and in the blood increase amino acid as results to Glomerular
filtrate contain large amount of amino acid → as we know 100% of amino acid should be
reabsorbed with Na so the amount of Na-Cl which reabsorbed more than 65% little Na-Cl
reach to medulla densa it seems that there's decrease in GFR so juxtaglomerular cells will
produce high amount of renin.

25
 Renal Physiology

‫المحاضرة الرابعة‬

 Primary force for most of reabsorption has to do with Na and k , at the end, there are
channels for 3 Na out and 2 k inside epithelial cells, that is why there is decrease of Na
inside by grading force, increase in absorption of certain elements like (cl , H 2CO3 , PO4 ,
H2O , Glucose , A.A , Lipids , small amounts of urea ,creatinine and lactate)

 In this point there are many ATPase pumps enhance secondary active transport for
these elements and other idea regarding a.a 100% will be absorbed in the proximal
convoluted tubule, also 100% will be absorbed (glucose, lactate and certain things).

 Water in proximal convoluted tubules has to do with aquaporin 1 this channels have
relation with osmosis. So it is freely permeable to H2O .so no change in Osmolarity
during movement of filtrate through PCT .

 Bicarbonate in proximal convoluted tubules around 90% will be absorbed (that has
related to acidosis and H+ secretion)

 The proximal convoluted tubule (PCT) cells play a crucial role in addressing acidosis,
which is the condition of increased acidity in the body. This process involves the
deamination and oxidation of glutamine, a molecule involved in nitrogen metabolism.
As a result of the deamination and oxidation of glutamine, two important products are
generated: two bicarbonate ions (HCO3-) and two ammonium ions (NH4+). These
products help regulate the body's acid-base balance. The ammonium ions are
subsequently secreted into the lumen of the tubule. Within the lumen, the ammonium
ions split into ammonia (NH3) and hydrogen ions (H+). This separation allows for the
removal of excess hydrogen ions, thereby reducing acidity in the body. Simultaneously,
the process enables the reabsorption of bicarbonate ions, contributing to the
maintenance of a healthy acid-base balance

 H will be combined with bicarbonate in the lumen by carbonic anhydrase enzyme to

produce carbonic acid.

dissociat
 Carbonic acid H2O + CO₂
e

 CO₂ will be reabsorbed into cells, inside the cells has to do with water to
convert to carbonic acid then H and bicarbonate.

26
 Renal Physiology

 Bicarbonate will be absorbed, H in proximal convoluted tubules will be excreted by

exchange with Na , so this area called Na dependent bicarbonate
reabsorption.

 the DCT is involved in the reabsorption of sodium, chloride, and bicarbonate ions, as
well as the secretion of hydrogen ions.

 Bicarbonate has to do with cells from ammonia side, Ca side , excretion of H

exchange with Na.
 This mechanism in total reabsorption of bicarbonate 90 % in PCT , but throughout
the nephron bicarbonate reabsorbed 100% .

 Reabsorption of phosphate in combining with Na because in proximal convoluted

tubule in basolateral there are 3 Na and 2 K which has to do with ATPase pump
which decrease concentration of Na inside.

 Phosphate exchange with Na which has to do with parathyroid hormone.

 Parathyroid hormone is polypeptide large molecules has receptors in basolateral

membrane like ADH, aldosterone
 parathyroid hormone receptor activates adenylcyclase.

activite
 Adenylcyclase will convert ATP to cAMP PKA

make
 PKA phosphorylation to channels of Na-Phosphate

excretion of phosphate.

 So, if phosphorylation occur in this area means body don't need phosphate

 PTH when acts on distal convoluted tubules will reabsorbed Ca+² which trigger in
hypocalcemia state. Not in PCT but in early part of DCT .

 Function of nephron from proximal to collecting ducts, but before this we have to
know mechanism of concentration or dilute the urine

 N.R of Osmolarity in plasma ≈ 300 mlosmol / L

 Uri osmoregulation means: urine make osmoregulation.

 Kidneys, nephrons and urine conc. to preserve normal Osmolarity inside plasma.

27
 Renal Physiology

▪️ factors such as sweating, decreased water intake, and respiration can contribute to
dehydration and hyperosmolarity. Sweating leads to water loss through the skin, while reduced
water intake fails to replenish the lost fluids. Respiration, particularly during physical activity or
in hot environments, also contributes to water loss through exhaled water vapor. When the
body loses more water than it takes in, dehydration occurs, resulting in an imbalance of fluid
levels. This imbalance leads to an increased concentration of solutes in the body's fluids, known
as hyperosmolarity. Both dehydration and hyperosmolarity can have adverse effects on the
body and its various functions. It is crucial to maintain proper hydration by drinking enough
fluids to prevent these conditions and support overall health.
In the condition of hyperosmolarity, like someone who is in the desert, the body responds by
synthesizing and activating specific receptors, such as osmoreceptors in the hypothalamus.
These receptors initiate hormonal mechanisms, including the release of antidiuretic hormone
(ADH) and activation of the renin-angiotensin-aldosterone system (RAAS), which help restore
fluid balance and regulate osmolarity.

 Osmole receptors in hypothalamus has relation with pituitary.

 Osmole receptors will stimulate vasopressin (ADH) secretion from posterior
pituitary glands.
 ADH reabsorbs water from distal tubules and collecting ducts ,so absorbed
water will decrease hyperosmolarity, means water back to the plasma to
decrease Osmolarity.
 ADH stimulate also thirst center which increase desire to drink water.

 solutes & water high Osmolarity

 solutes & water Low Osmolarity

 salutes = water iso Osmolarity

 when I drink water, I convert iso Osmolarity of plasma to hyposmolar plasma.

 Hyposmolar reaches to osmo receptors center in hypothalamus which make

suppression to ADH action.

 A decrease in ADH levels leads to reduced water reabsorption in the distal

tubules and collecting ducts, causing more water to be excreted in urine. An
increase in ADH levels has the opposite effect, promoting water reabsorption
and reducing water excretion.
 This area is the only region which has relation to ADH, so urine will be diluted
(↑ water).

28
 Renal Physiology

 Mechanism of concentrate or dilute urine:

1. ADH
2. Corticomedullary gradient (inside the interstitial medullary of nephron, there is
conc. higher than plasma)
 How this corticomedullary conc. gradient occur?
 How this gradient will be maintained?
So ADH & corticomedullary controls the conc. or dilatation of urine.

 Corticomedullary gradient:
How to occur= produced
How to maintain these gradient
 First how to occur

Corticomedullary gradient generated by

1- Countercurrent multiplayer system ( unique for nephron) occurs in Loop of Henle

Ascending part Descending part

1- Thin 2-thick Permeable to water via aquaporin 1

from lumen to interstitial space also
-Permeable for
paracellular tight junction in this
solutes (increase
area allow H2O passing
interstitial conc .

-decrease solutes
coc. of the tubule

-increase
interstitial
compartment
conc of solutes.

2- Urea recycling
I 300 mosm ( iso osmolality& good blood supply)
cortex

outer med

Inner
1200-1400 mosm
med

29
 Renal Physiology

 Concentration gradient:
Related to :
1) loop of hele
2) permeability of water
3) reabsorption solutes from thick part
65% H2O

65% Na reabsorbed in proximal tubules ( iso osmolality) .

65% CL

LOOP OF HENLE:

Hypertonic

o Decreased H2O
o Increased Nacl

Cell (K) some of K pushed back in the lumen

k
K
2CL
2CL
Na
Na

30
 Renal Physiology

 Thick part of ascending loop in basolateral membrane mainly active transport

impermeable to H2O and urea .
 Some K stays at lumen to depolarize the membrane and causes paracellular
transport of (Mg, Ca ) to Interstitium.

The Na/K ATPase pump located on the basolateral membrane of cells functions by actively
transporting three sodium ions out of the cell in exchange for two potassium ions being
transported into the cell. This pump helps establish and maintain a lower concentration of
sodium inside the cell compared to the outside. This concentration gradient is essential for
various cellular processes and indirectly affects osmotic pressure and the movement of
water across cell membranes. However, it does not directly produce a pressure gradient.

 Every new urine causes concentration difference between segments by about 200
mmHg as maximum.
 Continuous descend of urine concentration

 Paracellular transport:
When k+ goes back to inside the cell increase positive charge in the luminal surface.

 +ve charge  depolarization

 Electrical force (+ve of k)+(+ve of Ca&Mg)  Allow Ca and Mg to move paracellularlly
to I.S.E "intracellular environment"  increase conc. gradient of Ca & M

 Counter current multiplier System

31
 Renal Physiology

So the process is as follows:

The process begins with the reabsorption of salts in the thick part of the ascending limb
of the loop of Henle. This results in a high concentration gradient in the interstitial area.
When the newly formed urine enters the descending part of the loop of Henle, water is
absorbed from the tubules into the interstitial area through osmosis.

With each repetition of this process, the amount of salts reabsorbed in the thick part of
the ascending limb increases. This is because the urine reaching this segment is initially
concentrated (The reabsorption of water back into the interstitial area under the
influence of osmosis further concentrates the urine).

 reabsorption of solutes at the thick part of ascending limb: Na,k,2Cl  through

channels, While Mg, Ca  Paracellularlly.
 this Increase concentration gradient of intracellular area.
 When conc. Increases, the opposite area (descending limb) will be sensitive to
reabsorb water from lumens because inside them is for example (300) mosm, while
outside ,for example, (400) mosm  osmosis.
So, after water has been reabsorbed, the urine leaving the descending part would be
already concentrated (before reaching the thick part) . ‫ زي أول مرة‬300 ‫ مش‬400 ‫يعني هتكون‬

 400 allows the reabsorption of 100-200  ‫هذي تنضاف للذي قد امتص من أول‬
400=200+200
‫ ويضاف للذي قبلها‬I.S ‫وهكذا كل مرة يعاد امتصاص األمالح اكثر لمنطقة ال‬

600 8001000 1200 mosm

 So, generation of these gradient within cortex and medulla is related to Counter
Current Multiplier System.
How? one reabsorb water & the other reabsorb SOLUTES.
‫ ألن مرة واحدة يتم امتصاص األمالح والماء‬conc. gradient ‫ يعني بدون هذوال بيكون من الصعب عمل‬
.Regeneration ‫وانتهى لكن لما يستمر حدوث العملية سيستمر ال‬
 N.B:

o while the PCT, the descending limb of the loop of Henle, and the
DCT/collecting duct can have different levels of water permeability, the
ascending limb of the loop of Henle is impermeable to water ,This creates a
concentration gradient that allows for the reabsorption of water .

o While the ascending thick part is related to the reabsorption of solutes it is

impermeable to H20.
o Counter Current means one increase& one decrease
32
 Renal Physiology

o Multiplier each time more concentration 300400600800…. 1200

mosm/L.
 -Osmolarity mainly about Glucose& Na & k& urea, other solutes affect it, but have
minor effect.
o Urea is impermeable in all the following ascending thick loop of Henle and
DCT and cortical collecting duct in other part it is permeable.

 Urea recycling :
 At proximal(early) part of distal convoluted tubules, urine will be around 120-
100mOsm "hypo-osmolar"  Why! Because thick ascending is impermeable to H20
and urea :
reabsorbed %80 ‫الباقي من الماء‬ 20%
65%  reabsorbed at P.C.T

H2o
reabsorbed at descending
15% 
limb of loop of Henley

65%  reabsorbed at P.C.T

Nacl reabsorbed %90 ‫الباقي من الملح‬ 10%
reabsorbed at thick
25%  ascending limb of loop of
Henley
 So, 20% of water & 10% of solutes "Hypo-Osmolarity"  it means that there is less
than 300 mOsm of solutes per one liter of water.

 N.B:
 Descending part thin ascending part  urea permeable
 Thick ascending part early part of D.C.T water tight

 Thin ascending and thick ascending and DCT → H2O impermeable and late DCT and
CT its permeability is related to Hormones as ADH.

 In the early part of the distal convoluted tubules, there is active

reabsorption of sodium (Na+) and chloride (Cl-) ions through the
Na+/Cl- ATPase pump. This pump actively transports sodium and
chloride ions out of the tubular lumen and into the interstitial fluid.
 Approximately 5-6% of the filtered sodium and chloride ions are
reabsorbed in this segment of the distal convoluted tubules. This
reabsorption helps regulate the final concentration of sodium and
chloride in the urine.
33
 Renal Physiology


 So, from the initial filtered load of 100-120 units of sodium and
chloride, about 5-6 units are reabsorbed and returned to the
interstitial fluid, while the remaining percentage continues through the
nephron for further processing in the kidney.

- NOW the osmolality inside D.C.T : H2O 20 %, solutes 5% ←60 mOsm → (even more
hyposmolar)
- Because urea hasn’t been reabsorbed yet, it reaches to the late part still highly
concentrated.
- Before being excreted through urines, urea recycles 3-4 times

- urea recycling
- 1. Urea is reabsorbed from the medullary part of the collecting ducts: In the inner
medullary region of the kidney, urea can be reabsorbed from the collecting ducts
back into the interstitial fluid. This reabsorption occurs through specialized urea
transporters.

- 2. Urea solutes increase the concentration gradient of the interstitial area: The
reabsorption of urea from the collecting ducts contributes to the buildup of urea in
the interstitial fluid. This, in turn, helps establish and maintain the cortico-medullary
concentration gradient, which is important for the kidney's concentrating ability.

- 3. Once the concentration gradient reaches the required level, urea will be secreted
again through the thin tubules: When the concentration gradient in the interstitial
fluid reaches a certain threshold, urea can be secreted back into the tubular lumen
through the thin descending and ascending limbs of the nephron. This allows urea to
be excreted with urine.

- Overall, the recycling of urea, including reabsorption and subsequent secretion,

plays an important role in the maintenance of the cortico-medullary concentration
gradient and the concentration ability of the kidney.
The urea is impermeable in Thick ascending and DCT and cortical collecting duct but in
the medullary part of collecting duct preamble increase permeability by ADH action on
Uridine transport 1( UT1).
- Their cells have the ability to reabsorbed urea from inside to outside because in this
part urea inside is in high concentration related to other component of urine .

34
 Renal Physiology

- When urea is first released, it stays for a while to help establish the concentration gradient
of the medullary interstitial fluid, which accounts for about 30-40% of the corticomedullary
concentration gradient.
Thin descending ‫ ← تحديداً في ال‬tubule ‫ إلي داخل ال‬secretion ‫ يحدث له‬urea ‫االَن جزء من ال‬ -
and thin ascending loop of Henle
 Mechanism of urine dilution and concretion :
1) Corticomedullary conc. Gradient
- It produces by two things: -
- Multiplayer counter current system
- urea recycle
2) ADH
- The vasa recta is a network of blood vessels located in the medulla of the kidney,
between the inner and outer regions.
- In high flow conditions, there is a risk of solute washout, which can disrupt the
concentration gradient. However, the vasa recta helps maintain the concentration
gradient by preventing excessive solute loss.
- Urea is one of the factors that contribute to the generation of the corticomedullary
concentration gradient. It accumulates in the interstitial space and is reabsorbed by the
thin segments of the descending and ascending limbs of the nephron.
- Urea recycling involves the movement of urea from the collecting duct back into
the interstitium, enhancing the concentration gradient.
- Urea stimulates the Na+, K+, 2Cl- mechanism, which is involved in sodium and chloride
reabsorption in the thick ascending limb of the loop of Henle.
- Urea also aids in water reabsorption by interacting with aquaporin 1 channels,
thereby enhancing the concentration gradient.
- Structurally, the vasa recta forms a loop-like shape (∩), with the ascending limb
functioning as an artery and the descending limb as a vein. This arrangement allows for
countercurrent exchange, facilitating the preservation of the concentration gradient.
-
- The blood is decreasing from the cortex to medulla
Vasa recta to maintain the corticomedullary conc. Gradient ‫ عندها خاصية مميزة تساعد ال‬-
- It is a loop in shape not straight which have countercurrent exchange system as
below
- The blood flow decreases from up to down
- The permeability of these vessels allows:
1. OSMOSIS to water 2. Diffusion of salts
- The vasa recta has descending limb and ascending limb .
- In the descending limb the blood in high Osmolarity = 300
1200 moml/l = base ‫ يوصل في الـــ‬-
35
 Renal Physiology

‫بواسطة‬Osmolarity ‫ تزيد فتسمح بخروج الماء إلى الخارج لمعادلة الـــ‬Osmolarity ‫أول ما يبدأ ينزل تبدأ‬ -
osmosis ‫ال‬
- In the ascending limb is the site for exchange of salutes
Nacl ‫ يدخل فيها‬H2 O ‫في نفس اللحظة اللي خرج فيها‬ -
‫ وأيضا خروج‬osmolality ‫ يقلل‬lumen ‫ الذي يعود الى ال‬H2O ‫ ال‬ascending part ‫كل ما يطلع في ال‬ -
ml\osmol 325‫ يصل اخر شيء وهو‬osmolality ‫ يقلل ال‬solutes
It means that the loss is minor , approximately twenty-five does not affect the concentration.

The countercurrent exchanger mechanism:-

1. maintains that corticomedullary concentration gradient.
2. avoid= prevent the rapid move of solutes from the interstitial gradient.
N.B: In the loop of Henley —>multiplayer countercurrent: there is no excretion .
‫مكان يطلع ومكان يخرج‬
countercurrent exchanger :
‫نفس المكان يطلع ويدخل ويخرج‬
In the distal convoluted tubule (DCT), there are indeed two parts: the early part and the late
part. Each part has distinct mechanisms involved in the reabsorption and secretion of ions.
The early part of the DCT is responsible for fine-tuning the reabsorption and secretion of
various ions. It increase hypoosmolality .
The mechanisms in the early part of the DCT include:
1. Na+/K+ ATPase pump: This pump actively transports sodium (Na+) out of the tubular
lumen into the interstitial fluid and simultaneously transports potassium (K+) from the
interstitial fluid into the tubular lumen. This pump helps maintain the concentration
gradients of these ions.
2. Active reabsorption of Na+ and Cl-: In this process, sodium and chloride ions are
reabsorbed from the tubular lumen into the cells of the DCT through secondary active
transport mechanisms. Around 5% of filtered sodium and chloride ions are reabsorbed in
the early part of the DCT.
60 ml/osmol ‫ يصل الى‬late part of distal CT‫ يصل الى ال‬hypo-osmolar ‫لذلك يحدث‬ -
GS ‫ لل‬stimulation ‫ ويعمل‬polypeptide ‫ 》 هو عبارة عن‬PTH‫ 》يحفز ال‬hypocalcemia ‫اذا عندنا‬ -
stimulation of ‫ 》 تعمل‬cAMP ATP ‫ الذي يحول ال‬adylenate ‫ الذي يعمل تحفيز لل‬process
++Ca ‫ ويسمح لل‬certain mechanism ‫ ل‬phosphorylation ‫ يعمل‬protein kinase A
Reabsorption by opening of the Ca channel: The opening of calcium channels can be stimulated
by the exchange of hydrogen ions (H+) or the exchange of positively charged ions such as
sodium (Na+).

the late part of distal convoluted tubules has two types of cells:

36
 Renal Physiology

1. intercalated cells
2. principal cells.
Principle cell`s: it is a cell sensitive for ADH and basolateral membrane
Reabsorption of water in the renal tubules occurs primarily through the action of the
hormone antidiuretic hormone (ADH) and the presence of aquaporin 2 channels.
The process of water reabsorption in the renal tubules involves the action of antidiuretic
hormone (ADH) and specific aquaporin channels. When ADH is released, it binds to
receptors on the basolateral membrane of the collecting duct cells. This binding activates a
signaling pathway that involves the production of cyclic adenosine monophosphate (cAMP).
The elevated cAMP levels lead to the insertion of aquaporin 2 (AQP2) channels into the
apical membrane of the tubular cells, allowing water to move from the tubular lumen into
the cells. From there, water can pass through aquaporin 3 (AQP3) and aquaporin 4 (AQP4)
.channels in the basolateral membrane, exiting the cells and entering the interstitial fluid.
secretion in distal part for drug`s,creatinine,NH3…etc.

intercalated cells

A type B type
 

For acid For base For bs

 

Acidosis Alkalosis

C.A
Co2+H2O H++HCo3 H2O+ Co2 H2Co3
C.A=carbonic anhydrase enzyme. - H2Co3 by C.A  H+ +HCo3
-reabsorption of HCo3 &secretion of -reabsorption of H+ &
H+(exchange with K+)-Ammonia reacts
with H+ and produces ammonium execration of HCo3  urine to outside

Done ♤
All the best..

37
‫‪Renal Physiology‬‬

‫‪Team‬‬
‫أعضاء دائرة ال‪: Physiology‬‬
‫سارة الحميدي‬ ‫أمة الرحيم العرابي‬ ‫أسماء القدسي‬ ‫صفاء الجنيد‬
‫فاطمة الظلماني‬ ‫رؤى الميرابي‬ ‫البتول الغويدي‬ ‫زينب المزيقر‬
‫حنان المعلم‬ ‫أميرة غبيس‬
‫علي العمراني‬ ‫باسم الحبيشي‬ ‫محمد السالمي‬ ‫أحمد الحميدي‬

‫محمد رزوم‬

‫أعضاء اللجنة االلكترونية‪:‬‬

‫رضوان القفلي‬ ‫محمد المخالفي‬ ‫محمد الزاهري‬ ‫عبداالله الصوفي‬
‫جواد منذر‬ ‫احمد الكمال‬ ‫هاشم الشرقي‬ ‫صدام حيدره‬
‫رؤى االنسي‬ ‫امل منير‬ ‫هنادي مفتاح‬ ‫االء شمسان‬

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