Functions of the kidney

The kidney have many important functions including:

1. Get rid of waste (ingested or metabolized) and foreign chemicals
- Such as:
a- Urea from amino acids metabolism
b- Creatinine which is a byproduct in the muscles
c- Uric acid from nucleic acid metabolism
d- Bilirubin from Hb breakdown
e- Pesticides, drugs, food additives

2. Control the volume and composition of body fluid

- Excretes excess substances and preserve the depleted ones to maintains the homeostasis
3. Regulation of water and electrolyte balances
4. Regulation of fluid osmolality
5. Regulation of Acid - Base balance
- Excreting acids or bases in the urine to regulates the acidity of the blood to be ranged between
(7.35 – 7.4) → maintains of the homeostasis
- How we regulates the acid base balance?
➔ Buffering System of the blood
✓ Through HCO3- & H2CO3 in the blood
➔ Respiratory System
✓ Through HCO3- & H2CO3 in the alveoli
➔ Renal System
✓ It slower acting than the other two mechanisms, but they have a more powerful effect
on pH.
6. Regulation of Arterial pressure
a- Long-term: excreting Na and water
b- Short-term: renin secretion
7. Gluconeogenesis (Glucose synthesis)
- From amino acids and other precursors during prolonged fasting

8. Endocrine functions:
- Producing of erythropoietin
➔ To regulates the production of RBCs
- Producing of renin
➔ To regulates the blood volume and blood pressure
- Producing of vitamin D3
➔ Produce the active form of Vit-D3

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 Physiological anatomy
General organization:
- We have 2 kidneys in the posterior side of our body,
outside peritoneal cavity.
- Wights about 150 gm, as size of clenched fist, each one
consists of:
➔ Outer cortex
➔ Inner Medulla, contains:
✓ Renal pyramids
✓ Renal papilla
✓ Renal pelvis
✓ The major and minor (calyx) calices

➔ As urine is formed, it drains into the renal pelvis and is channeled into the ureter.
➔ The urine is stored in the bladder (‫)المثانة‬.
➔ It is emptied through urethra (‫)االحليل‬.

Inside the kidney, we find the nephron

Nephron
- It is the functional unit of the renal system.
- There are 1 million/kidney
➔ After 40year old. 1% each/year decrease and cannot regenerated.
➔ But they have the ability to divides under certain circumstances.
➔ 50% or less of nephrons are enough to do the function.

In real life we don’t use all of our 2 million nephrons to filtrate the plasma
of the blood
‫وحتى فعليا يمكن لو بدك تجيب كلية وتشوفها هل هي بتشتغل في الظروف الطبيعية كلها رح‬
!‫تالقي انه ¼ النفرونات بس بشتغلو يعني نظريا الواحد بقدر يعيش بربع كلية فقط‬

Components of the Nephron

❖ Vascular Component:
Collection of B.V that surround nephron
▪ Afferent arteriole:
➔ Control the blood flow to kidney
➔ Enter the Bowman’s capsule and form:
➔ Glomerulus: is a special type of capillaries that are:
✓ Highly fenestrated capillaries
✓ Allows filtration of plasma

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 ▪ Efferent arteriole:
➔ Take the remaining filtered plasma
➔ Exit from the Bowman’s capsule and form:
➔ Peritubular capillary that Surround the whole nephron

❖ Tubular Components
▪ Bowmans’s capsule
▪ Proximal convoluted tubule
▪ Loop of Henle
➔ U-shaped, hair-pen structure
➔ Has two parallel segments – ascending & descending limb – that fits with its function (produce
concentrated urine)
▪ Distal convoluted tubule
➔ Passes btw the afferent & efferent arterioles

▪ Collecting duct
➔ Collects the final form of urine from many nephrons & sends it to be excreted out.
➔ In certain conditions we reabsorbed water from it.
➔ (8 to 10) ducts join to form single large collecting duct
Types of nephrons:
Cortical Nephrons (Major)
➔ Most of their structure is found in the cortex
➔ Small part of loop of Henle in the medulla
➔ They are most nephrons in the human kidney (80%)
➔ Most of the filtration & reabsorption will happen here
➔ Receive most of the renal blood flow (95%)

▪ Juxtamedullary Nephrons (Minor)

➔ Originate very close to medulla then extend down deep in
➔ They are limited in number (20%) & blood supply (5%)
➔ Have longer loops of Henle
✓ Responsible for diluted or concentrated urine
depending on the body state
➔ Involved in concentrating the urine to help us preserve
water
➔ May found in creatures that live in desert in more numbers

Vasa recta:
➔ The peritubular capillary around the loop of Henle in
Juxtamedullary Nephrons, it is hair-pen like structure &
responsible for maintaining the concentration gradient in the medulla.

 Note: Each nephron operates & work independently

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Renal blood supply:
- Blood flow to the kidneys is normally about 22% of cardiac output or 1200 ml/min
- Renal artery enters the kidney & branches progressively to form Afferent arterioles
➔ Which lead to the glomerular capillaries (‫)الكبة‬.
- The distal ends of the capillaries of the glomerulus form the Efferent arteriole
➔ Which leads to peritubular capillaries, that surrounds the renal tubules.
 Notes:
▪ The waste products are transported by blood dissolved in the plasma – water-like component – so
how much plasma will reach the kidney each min?
➔ Plasma is about 55% of blood (3L)
➔ the blood volume that reach the kidney each min = 1200
➔ the plasma volume that reach the kidney each min = 1200 * 0.55 ≈ 625 ml
▪ The 22% of CO for:
➔ Filtration of blood -plasma-
➔ Supply the nephrons by nutrients and O2

Urine formation
- The urine formation consists of 3 main processes:
➔ Glomerular Filtration
➔ Tubular reabsorption
➔ Tubular secretion

- Then the final form of urine is formed and ready to be

excreted out the body:
➔ Urinary excretion rate =
filtration Rate - reabsorption Rate + secretion Rate
Glomerular filtration ‫الترشيح‬
- The process in which plasma is filtered from glomerular capillaries into Bowman’s capsule
- It is a random process in which the good and bad substances will be filtrated into the tubular side
of the nephron
- The filtered fluid (filtrate) is: Protein free and devoid of cellular elements

How is it formed?
- Filtration process depends on many forces that exerted on the plasma
- Those forces are:
➔ Bowman's capsule hydrostatic pressure
➔ Glomerular capillary colloid osmotic pressure B.V
➔ Glomerular capillary hydrostatic pressure

Will discussed later in this lecture

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- Glomerular filtrate is produced at rate of 125 ml/ min (180 L/day).
➔ This means that our plasma is filtrated 60 times per day (180/3 = 60).
- Again, the plasma volume that reach the kidney each min ≈ 625 ml/min
➔ And the filtrated plasma = 125ml/min

- Thus, 20 % of plasma is filtered and 80% are not filtered & passes into efferent arteriole then
peritubular capillaries
𝐺𝐹𝑅
Filtration fraction = = 125/625 = 1/5 = 20%
𝑅𝑒𝑛𝑎𝑙 𝑝𝑙𝑎𝑠𝑚𝑎 𝑓𝑙𝑜𝑤

- The high GFR depends on:

➔ High rate of kidney blood flow (Glomerular hydrostatic pressure)
➔ Special properties of glomerular capillary membranes.

Tubular reabsorption ‫إعادة االمتصاص‬

- The process in which the Good-filtrated substances move from tubules
into the blood of peritubular capillaries
- The reabsorption rates of most substances are very high.
➔ 99% of filtrate will be reabsorbed (180L filtered, 178.5L are
reabsorbed)

Tubular secretion ‫االفراز االنبوبي‬

- Selective process in which small quantity of substances are secreted from peritubular capillaries &
enter the tubules.
- Those substances that must be cleared from the blood:
➔ The end products of metabolism, such as urea, creatinine, drugs, uric acid
Urine excretion ‫االخراج‬
- The process in which the urine excreted out of the body

- How the body differentiates the bad substances from the good substances in the reabsorption
process?
Renal handling:
- There are 4 types of substances depending on how good the substance for the body:
➔ Substance is freely filtered but neither reabsorbed nor secreted
✓ Those substances are excreted out of the body at rate equal to filtration rate
✓ Like = Creatinine (toxic) and inulin
✓ Clearance of creatinine and inulin = GFR
➔ Substance is freely filtered, but part of is reabsorbed.
✓ Like most electrolytes and urea
➔ Substance is freely filtered but totally reabsorbed
✓ Like Amino Acids & glucose and vitamins
➔ Substance is freely filtered and is not reabsorbed but secreted
✓ H+ and K+ and para-amino-hyperopic-acid (PAH)
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 Filtration
Again,
- It is the process in which plasma is filtered from glomerular capillaries into Bowman’s capsule
- It is a random process in which the good and bad substances will be filtrated into the tubular side
of the nephron
- The filtered fluid (filtrate) is:
➔ Similar to plasma but
✓ Protein free and devoid of cellular elements
✓ Less Ca++ and fatty acids because they are bound w/proteins

- The factors that affect the filtrate inside the nephron are the forces and pressure
Glomerular Filtration Forces
Glomerular blood pressure
- Glomerular blood pressure (hydrostatic) is about 60mmHg
- Favors (enhance) filtration
➔ Push water from glomerulus into Bowman’s capsule
leading to increase water & pressure in it
➔ Leaving proteins inside the blood vessel leading to
formation of colloid (osmotic) pressure
Colloid (osmotic) pressure
- Decrease (opposes) the filtration
➔ It is about 32 mmHg
Bowman’s capsule pressure
- Decrease (opposes) the filtration
➔ It is about 18 mmHg

❖ NET filtration
- We have many different forces that affect the filtration which are:
➔ Glomerular blood pressure (+), Bowman’s capsule pressure (-), Colloid (osmotic) pressure (-).

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- By summation of all of them, the NET filtration = 10mmHg, which is responsible for formation of:
➔ Filtrate inside the Bowman’s capsule (‫)السائل الراشح‬
➔ GFR = 125ml/min

- The net filtration favors filtration

➔ How can we increase the filtration rate? By monitoring the forces that affect net filtration, but:
✓ GFR regulation is mainly due to changes in glomerular hydrostatic pressure
✓ The other forces are constant in normal conditions & may change during diseases

- Are there other factors that affects the filtration rather than the forces above?
➔ The answer is yes which is the filtration barrier

Filtration barrier
- Is the barrier that surrounds the glomerular capillaries, consists of:
➔ Endothelium
✓ Very fenestrated & allow only the small
substances to pass through
➔ Basement membrane
✓ Consists of collagen & Proteoglycan
✓ Has -ve charge
➔ Epithelium (podocytes)
✓ Form filtration slit

- This structure make the glomerulus has 500 folds more filtration in comparison to other types of
capillaries

Filterability “‫”مهم‬
- Depends on size and charges, for example:
➔ The large Molecules can’t pass but the small ones can
➔ The negatively charged molecules can’t pass but positively charged molecules pass

Which of the following of characteristics of a hypothetical molecule favors less filtration

through the nephron filtration membrane?
a. Small molecular weight and neutral charge
b. Small molecular weight and negatively charged
c. Small molecular weight and positively charged
d. Large molecular weight and negatively charged
e. Large molecular weight and positively charged

- Back to our question, “are there other factors that affects filtration rather than the forces? “
➔ The filtration depends on the filtration barrier that is have relatively constant effect between the
individuals

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 ml/min
➔ Thus, we have filtration constant “Kf = 12.5 ”
mmHg
✓ GFR = K* Net filtration pressure
- Net filtration pressure = 10 mmHg & Kf = 12.5 ml/min/mmHg
ml/min
➔ GFR = 10 mmHg x 12.5 = 125 ml/min→ 180 L/day
mmHg

- Why we have a huge GFR?

➔ To ensure that Most waste product removed rapidly
➔ Allow all body fluids to be filtered and processed by kidneys many times each day (precise &
rapid control of volume & composition).
Factors affect GFR
- Bowman's capsule hydrostatic pressure (‫)عكسيا‬
➔ Stones increase it
- Glomerular capillary colloid osmotic pressure (‫)عكسيا‬
➔ 32 mmHg and this pressure is determined by:
a. Arterial plasma colloid osmotic pressure
b. Fraction of plasma filtered (filtration Fraction)
 Increase the plasma filtered = increase plasma proteins inside capillary
 Increase the Glomerular capillary colloid osmotic pressure
 Note:
-  Filtration Fraction =  Glomerular colloid osmotic pressure = ↓GFR

- Glomerular capillary filtration coefficient (‫)طرديا‬

➔ Chronic uncontrolled hypertension & DM decrease coefficient and then GFR

- Glomerular capillary hydrostatic pressure: ( ‫)طرديا‬

➔ This pressure is determined by:
a. Arterial pressure
 More arterial pressure more hydrostatic pressure more GFR
b. Afferent arteriolar resistance
 More resistance (vasoconstriction) decrease the hydrostatic pressure → ↓ GFR
 Low resistance (vasodilation) increase the hydrostatic pressure →  GFR

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 c. Efferent arteriolar resistance
 More resistance (vasoconstriction)
increase the hydrostatic pressure but has
different effect on GFR, Known as
Biphasic effect:

Biphasic effect
- Firstly, Mild to Moderate vasoconstriction of efferent
arteriole leads to:
➔  Hydrostatic pressure =  GFR
- Then, Severe vasoconstriction of efferent arteriole leads to:
➔ ↓ Renal artery = ↓ Hydrostatic pressure = ↓ GFR
➔ Also, due to  GFR the filtration fraction will be increased This is called
✓ Then the colloid osmotic pressure of the glomerulus will increase Donnan effect
✓ That will decrease the GFR.

Regulation of Renal blood flow and GFR

It is Controlled by:
Autoregulation of GFR and Renal blood flow:
- Involves intrinsic responses to regulates the blood pressure and GFR
- Change of Arterial pressure between (75 - 160 mmHg) have
negligible effect on the GFR
➔ After this range when pressure increase GFR increase
➔ Leading to increase the amount of urine

- Why Is it important to regulate the GFR when pressure increase?

➔ Assume that the pressure is increased 25% without autoregulation this will lead to
✓ Increase the GFR by 25% from 180L/day to 225L/day
➔ If reabsorption constant (178.5) so urine 46.5L/day
- Autoregulation and changes in reabsorption will not cause significant increase in urine output

Mechanisms of Autoregulation:
1. Tubuloglomerular feedback:
Juxtaglomerular Apparatus
▪ This structure consist of:
➔ Distal convoluted tubule
➔ Afferent arteriole
➔ Efferent arteriole

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 Macula Densa acts on afferent arteriole
▪ Macula Densa
➔ Elongated cells of the distal tubule
➔ Come very close to afferent & efferent arteriole
➔ Senses any change in NaCl concentration & filtrate volume in DCT
➔ Stimulates the secretion of a locally active vasopressor which acts on afferent arteriole
▪ Juxtaglomerular cells.
➔ Modified smooth muscles of afferent arteriole
➔ Receive input from the sympathetic NS to control BP through renin secretion
➔ Secrete renin hormone: that lead to increase the BP by angiotensin II
Tubuloglomerular feedback Juxtaglomerular cells acts on
Efferent arterioles
-  blood pressure =  GFR =  NaCl
➔ This increase will be sensed by Macula densa
✓ Macula densa: release vasoconstrictor to afferent
arteriole to ↓ GFR

- ↓ blood pressure = ↓ GFR = ↓NaCl

➔ This decrease will be sensed by Macula densa that will:
✓ Release vasodilator to afferent arteriole to 
GFR
✓ Stimulates the Juxtaglomerular cells to release
the Renin to activate Angiotensin II
• Angiotensin II work on Efferent arteriole
and constrict it to  GFR
2. Myogenic autoregulation:
- Myogenic theory:
➔ When pressure increased this will increase the stretch on muscle
➔ Increase muscle contraction

-  blood pressure =  GFR

➔  stretch = vasoconstriction = ↓ GFR

- ↓ blood pressure = ↓ GFR

➔ ↓ stretch = vasodilation =  GFR

Extrinsic mechanisms to regulate the renal blood flow & GFR

1. Sympathetic N.S:
- Strong activation:
➔ Vasoconstriction lead to Decreases flow and GFR
- Moderate activation:
➔ Negligible effect
- While parasympathetic nervous system does not have any influence on the kidneys.

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2. Hormonal and autacoid:
- Norepinephrine, epinephrine & endothelin
➔ Vasoconstrictors that constrict renal blood vessels and decreases GFR

- Angiotensin II constricts efferent arterioles

➔ increase GFR – increase Na & H2O reabsorption
- Endothelial - Derived Nitric oxide
➔ Cause vasodilation so decreases arteriolar resistance and increase GFR
- Prostaglandins & bradykinin
➔ Cause vasodilation so decreases arteriolar resistance and increase GFR

3. Other factors:
1. increase protein intake
➔ increase blood flow and GFR
➔ increase the amino acids reabsorption along with Na
➔ Decreases Na
➔ Autoregulation - Tubuloglomerular feedback

2. Increase Blood glucose: same mechanism

The End

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