URIN 313 BLOCK

Academic Year: 1441 H / 2019 - 2020 G

Metabolic Functions of The Kidney

 REVIEW

The NEPHRON
FUNCTIONAL UNIT OF THE KIDNEY
 REVIEW Urine Formation

FILTRATION REABSORPTION SECRETION

Glomerular Filtration Rate (GFR) = 125 ml/min = 180 Litre / Day

Urine Formation Rate = 1 ml / min = 1.5 Litre / Day
 PHYSIOLOGICAL REVIEW: FUNCTIONS OF the KIDNEYS

1- GLOMERULAR FUNCTIONS

Glomerular Filtration Rate (GFR)

Volume of blood filtered per minute
125 – 150 ml/minute
Glomerular filtrate contains: water, electrolytes, small dissolved solutes (as glucose,
amino acids, urea, creatinine, low molecular weight proteins)

Factors that facilitates filtration:

High Pressure of Glomerular Capillaries
Semipermeable Glomerular Basement Membrane (Molecular Size Cutoff 66 KD)
 PHYSIOLOGICAL REVIEW: FUNCTIONS OF the KIDNEYS

2 TUBULAR FUNCTIONS
Proximal Convoluted Tubules (PCT)
Reabsorbs:
The bulk of each valuable substances back to the blood
75% of Water, Sodium & Chlorides
100% of Glucose (according to renal threshold)
Almost ALL Amino Acids, Proteins & Vitamins
Variable Amounts of Urea, Creatinine, Uric
Acid, Ions (Mg, Ca2+, , K-, HCO3-)
Secretes:
Products of kidney tubular cells metabolism:
H+ & drugs, etc

Distal Convoluted Tubules (DCT):

Effect small adjustments to achieve electrolytes & acid-base homoeostasis under the control of
ADH & ALDOSTERONE

3 Elimination of Non-Protein Nitrogen (NPN) Compounds:

(UREA, Creatinine & Uric Acid)
NPNs are waste products formed in the body as a result of metabolic degradation
of nucleic acids, amino acids & proteins
PHYSIOLOGICAL REVIEW: FUNCTIONS OF the KIDNEYS

4 Water & Sodium Balance:

Regulation by ADH & Aldosterone Hormones
Hypovolemia : (↓ Water & Sodium in Blood)
Dehydration → ↓ Bl. Volume → Aldosterone
Release → ↑ Sodium Reabsorption →
↑ Plasma Osmolarity → ++ ADH Release
→ Water Tubular Reabsorption →
Correction of hypovolemia

5 Pottasium Balance:
- Aldosterone increase or decrease (to
increase potassium reabsorption or excretion)
- In Metabolic Alkalosis, K+ competes with H+
x
for exchange with Na+ in PCT
6- Acid-Base Balance:
1- Regeneration of Bicarbonate (Carbonic Anhydrase System)
2- Excretion of Metabolic Acids (H+ ions)
3- Ammonia (NH3) Production in Renal Tubules from glutamine (by
glutaminase). Ammonia reacts with H+ to form ammonium (NH4-)
which can be reabsorped (Ammonium Trap)
PHYSIOLOGICAL REVIEW: FUNCTIONS OF the KIDNEYS

7- Calcium Homeostasis:
1- Activation of Vitamin D by Renal 1a Hydroxylase
The key regulatory enzyme in vitamin D activation is the 1a hydroxylase enzyme
produced by the kidney.
Vitamin D3 (Cholecalceferol) is hydroxylated in the liver to 25 hydroxycholecalciferol
(25 HCC)
Then, the renal 1 hydroxylase converts 25 HCC to 1, 25 dihydroxycholecalceferol
(1, 25 DHCC), which is the active form of vitamin D.
The main physiological role of active vitamin D (1, 25 DHCC) is promoting calcification
of bones (adding calcium) mainly through increasing calcium absorption from GIT.
In Renal Insufficiency,

Active vitamin D is not sufficient ending in renal rickets (poor calcification of bones).
The resulting hypocalcemia due to vitamin D deficiency may end in secondary
hyperparathyroidism i.e. increased production of the parathyroid hormone (PTH).

2- In cases of ↓ blood calcium, PTH decreases calcium loss by ↑ calcium

reabsorption

renalosteodystrophy
 SUMMARY REVIEW:
PHYSIOLOGICAL of FUNCTIONS OFOF
FUNCTIONS THE
the KIDNEYS
KIDNEYS

8 Endocrinal Functions:
- Renin-Angiotensin- Aldosterone Pathway
- Activation of Vitamin D by 1  Hydroxylase Enzyme
- Erythropoietin

9 Metabolic Functions:
- Synthesis of Creatine (Guanidoactetic Acid)
- Synthesis of Carinitine (for FA oxidation)
- Synthesis of Glucose in Prolonged Fasting (Gluconeogenesis)
- Energy (ATP) Production for Renal Functions:
- In Fed-State: Glycolysis (Aerobic Glucose Oxidation & CAC)
- In Fasting State: Fatty Acid Oxidation & Ketone Bodies Degradation (Ketolysis)
- Synthetic Functions:
- Synthesis of Cholesterol & Fatty acids
- Synthesis of Amino Acids
- Degradation of Amino Acids
 Functions of the Kidney

Water & Excretion of

NPN Compounds
Electrolytes Urea, Creatinine, Uric acid
Balance & ‘Foreign’ molecules as
Drugs

Acid-Base Metabolic
Balance
Functions
Endocrinal Functions
• Production of certain enzymes (e.g. Renin)
• Endocrinal Roles:
Activation of Vitamin D
Production of
Erythropoietin
Metabolic Functions of The Kidney
 REVIEW

Kidneys receive 25 % of Kidney tissue represents

the cardiac output less than 0.5% of the body
& 10 % of O2 weight
consumption
25% of
COP

Body
Weight

This is required for the synthesis of ATP needed to reabsorb most of

the solutes filtered through glomerular membranes
 SOURCES OF ENERGY OF THE KIDNEY

Kidney STORES
of
Glycogen
Phosphocreatine (CP)
Lipids
are Very Low Energy Sources

So

kidney must get its energy requirement from

Circulating Fuel Substrates
as Glucose, Fatty Acids & Ketone Bodies
SOURCES OF ENERGY OF THE KIDNEY

FED STATE STARVATION

Glucose Oxidation Fatty Acids Oxidation

Glycolysis &

& Ketone Bodies

Degradation
Citric Acid Cycle
(Ketolysis)
 Carbohydrate Metabolism
in the Kidney

Glucose Oxidation Glucose Synthesis

Aerobic Glycolysis, Gluconeogenesis
Glycolysis + Citric Acid Cycle Synthesis of glucose from non-
& carbohydrate sources
PPP as lactate, glycerol & amino acids
PhosphatePentosePathway (esp. glutamine)
Pentoseshunt
oxidizeglucose itbreaksglucosbe udtoesn'ptroduc e

ATP
 Hormonal Regulation of
Renal Glucose Metabolism

Insulin
- Stimulate Glucose Oxidation (Glycolysis)
- Inhibits Renal Gluconeogenesis
-

Epinephrine:
- Stimulates Renal Gluconeogenesis

Glucagon
- NO EFFECT on renal glucose metabolism
 Glucose Metabolism in Fasting

Early fasting (First 12 -18 Hours):

Source of glucose in blood is mainly by liver glycogenolysis

18 – 60 Hours of Fasting:
Source of blood glucose is mainly gluconeogenesis (in liver & kidneys)

After 60 Hours of Fasting:

Liver gluconeogenesis release is decreased by 25%
So, liver cannot compensate for the kidney to preserve normal blood glucose
levels in patients with renal insufficiency during prolonged fasting.
This may explain why patients with renal failure develop hypoglycemia
 Lipid Metabolism in the Kidney

Lipid metabolic pathways occur in the kidneys:

1- -Oxidation of Fatty Acids
2- Synthesis of Carnitine : to transport of FA to mitochondria oxidation
3- De-novo Synthesis of Fatty Acids

04-Degradation of Ketone Bodies (Ketolysis)

4- De-novo Synthesis of Cholesterol
5- Activation of Glycerol to Glycerol 3-
Phosphate (by Glycerol Kinase)
 Protein Metabolism in the Kidney
Important Amino acid Metabolic Pathways in the Kidneys:

1 Excretion of Urea in Urine

Urea is synthesized in the liver from ammonia
Ammonia is products of amino acid catabolism

2 Degradation of Glutamine by Glutaminase

Enzyme
Glutamine produced in most organs (from amino acid metabolism) are
degraded into glutamate & ammonia in the kidney.
Ammonia produced is important in Acid base Balance

3 Creatine Synthesis (First Step) & Excretion f Creatinine (End

Product)
- Synthesis of guanidoacetic acid from amino acids glycine & arginine
(First Step of creatine Synthesis)
- Excretion of creatinine in urine
 Synthesis of Creatine by kidneys & liver

Methylation of guanido acetic acid to creatine

in the liver

1
Formation of guanido acetic acid
From amino acids glycine & argenine
In the kidney
Role Ammonia Metabolism in the Kidney in Acid
base Balance

Ammonia (NH3) is produced in Cells of Renal Tubules:

By the enzymes:
• Glutaminase (as discussed before)
• Glutamate dehydrogenase

In the Tubular Lumen, NH4+ is produced from Ammonia (NH3) & H+ :

Ammonia (NH3) + Hydrogen ions (H+ ) = Ammonium ions (NH4 )
+

This reaction is favored at the acid pH of urine.

The formed NH4+ in the tubular lumen can not easily cross the cell membranes & is trapped
in the lumen to be excreted in urine with other anions such as phosphate, chloride &
sulphate.(forming ammonium phosphate, ammonium chloride & ammonium sulphates).

NH4+ production in the tubular lumen accounts for about 60% excretion of hydrogen
ions associated with nonvolatile acids.
Source of H+ required for NH4+ formation:

1. Glomerular filtrate
2. The effect of carbonic anhydrase enzyme during the synthesis of carbonic acid
in the tubular cells, H+ is secreted into the lumen by the Na+/ H+ exchanger.

In renal insufficiency, the kidneys are unable to produce enough NH3

to buffer the nonvolatile acids leading to metabolic acidosis