Renal Metaboi

Question 1

What are the functions of the kidney?

Answer 1

-get rid of toxins and waste products
- retain substances needed by our bodies and reabsorbed glucose aminoacids and other small molecules
-maintain water and electrolyte balance
- regulate blood pressure
- They produce various hormones as erythropoitene , renin , and activate vitamin D

Question 2

What are the functions of the kidney?

Answer 2

-get rid of toxins and waste products
- retain substances needed by our bodies and reabsorbed glucose aminoacids and other small molecules
-maintain water and electrolyte balance
- regulate blood pressure
- They produce various hormones as erythropoitene , renin , and activate vitamin D

Question 3

What are the major fuels used by the kidney in the different metabolic states ?

Answer 3

During well fed: the major fuel is glucose
During fasting state: the major fuels are fatty acid and ketone bodies

Question 4

What are the different metabolic pathways of glucose in the different regions of the kidney?

Answer 4

Renal cortex which is richly supplied by oxygenated blood oxidise glucose completely into CO2 and H2O by aerobic glycolysis and TCA cycle

Renal Medulla which is poorly supplied by oxygenated blood oxidises glucose anaerobically into lactic acid by anaerobic glycolysis

Question 5

Explain the role of kidney in glucose homeostasis

Answer 5

• Role of kidney i n glucose homeostasis :
  1uptakeof
  glucose
  2Reabsorption of glucose
  3Gluconeogenesis
  1st ⇒ uptake of glucose
  uptake of glucose from the Circulation to satisfy its energyneeds
  2nd ⇒ Reabsorption of filtered glucose & pumping it backinto the to Conserve glucose Carbon Filtered glucose in the glomeruli
  is reabsorbed Completely in the PCT by Sodium dependent glucose transporters (SGLT) Circulation approximately 90% of the filtered glucose is reabsorbed in the 1st Segment of thePCT by SGLT-2 The remaining 10% is reabsorbed in the 2nd &3rd segments by SGLT-1.Then glucose is released into the
  Circulation by glucose transporters “ GLUTS “ at the basolateral membrane
  of epithelial cells of PCT.

3rd gluconeogenesis ⇒ The kidney is involved in release of glucose into the Circulation during Starvation by gluconeogenesis
Gluconeogenesis occurs in the renal??Cortex as it Contains the gluconeogenic enzymes including glucose_6_phosphatase.

Question 6

Mention a Clinical application related to the transport of glucose by SGLT-2

Answer 6

SGL T-2 inhibitors are recently developed drugs for Controlling hyperglycemia in Type2 DM by increasing glucose execration in ~urine

Question 7

what are the substrates for gluconeogenesis?

Answer 7

1st⇒ Lactic acid
which is produced from anareobic tissues as RBCs, Renal medulla &muscle during Severe exercise . Lactate is metabolised predominantly in the Liver but the rest ofLactate is
metabolized in the kidney to generate glucose Via
gluconeo genesis.1

2nd⇒ Glycerol which is produced from Lipolysis
of TAGS” Liver & kidney have active
glycerol kinase”

3rd⇒ Glutamine
During Starvation, protein Carbon becomes the major Source of glucose
Alanine & glutamine account forover
50% of the total amino acids released
During starvation , a major site of glutamine metabolism isthe kidney. This process Serves 2 important functions:
lst the Nitrogen of this glutamine is eliminated as Ammonium ions (NHIT) in urine & the carbon skeleton is utilized in gluconeogenesis.

Question 8

GR: Patients with Renal failure develop hypoglycemia during prolonged starvation.

Answer 8

After An overnight fast (14-16 hrs) 75_80% of glucose released into the Circulation is Synthesized by the liver while the rest ofglucose is released from thekidney by renal gluconeogenesis

• In Case of prolonged fasting> 18hrs hepatic release of glucose decreases by 25% as Liver glycogen becomes depleted.

kidney Contribution in bloodglucose production Via gluconeogenesis is increased to “45%” .
In patients with renal insufficiency liver cannot Compensate to
maintain normal blood glucose Level
“normoglycemia” in these patients during Prolonged
fasting.

Question 9

where do active metabolic
Pathways of Lipid metabolism take place in the kidney?

Answer 9

It Takes place in the renal Cortex which is richly supplied
by oxygenated blood.

Question 10

what are the metabolic pathways of Lipid metabolism that take place in the renal Cortex?

Answer 10

1 Fatty acid oxidation “B- oxidation pathway.
2 Ketone bodies through ketolysis

Question 11

Define ⇒ Gamma glutamyl Cycle “ Meister Cycle”

Answer 11

It is a cycle that is used by the
kidney for the reabsorption
of Aminoacids from the
glomerular filtrate.

Question 12

what are the enzymes involved in miester Cycle/ Y - glutamyl Cycle ?

Answer 12

Y - glutamyl trans peptidase
Y_glutamyl Cyclortransferase
Oxi -prolinase⇒ utilizes ATP
y_glutamyl Cysteine Synthetase⇒ utilizes ATP
glutathione synthetase⇒ utilizes ATP

Question 13

How do the enzymes of Miester cycle perform their functions?

Answer 13

These enzymes make a series of catalytic reactions which involve the Synthesis & degradation of glutathione & the Coupled uptake & release of free AminoAcid.

These reactions take place as follows…
Glutathione “glutamyl-cystenyI- glycine” + AA ⇒ Y_glutamyl AA Y_glutamyltranspeptidase.
Y_glutamyl AA ⇒ free AA & oxyproline “Y- glutamyl Cyclotrans- ferase”
Oxy proline ⇒ glutamate “ Oxy prolinase utilize ATP
&liberate ADP & Pi “

glutamate + Cysteine ⇒ glytamyl Cysteine glutamyl cysteine Synthetase”

y_glutamyl Cysteine + glycine ⇒ glutathione by glutathioneSynthetase utilizing ATP

Question 14

Mention I Clinical application based on Meister Cycle

Answer 14

Cisplatin is a widely used Chemotherapy drug which is nephro toxic as a result of binding of Cisplatin to glutathione & the subsequent metabolism of Cisplatin -glutathione Complex by Y_glutamyl transpeptidase to Cisplatin cystanyI Complex in PCT which is Nephrontoxic

Question 15

what is L-carnitine?

Answer 15

It is an aminoacid derivative that plays an essential metabolic role as it tansports Long_ chain Fatty acids into the mitochondriaI matrix “Carnitine Shuttle “ So they Can be broken down through
B- oxidation to produce
Acetyl -COA to obtain usable energy Via the
citric acid cycle.

Question 16

which tissues require Carnitine the most?

Answer 16

It is Crucial forenergyproduction in tissues which depend
on Fattyacid oxidation as Skeletal muscle &cardiac muscle in which 95% of Carnitine is stored.

Question 17

what are the different Sources of L-carnitine?

Answer 17

Exogenous ⇒ red meat & dairy products in diet.
Endogenous ⇒ Biosynthesis ofL- carnitine from Aminoacid Lysine &methionine Primarily in the Liver &kidney then released to peripheral tissues.

Question 18

Describe Carnitine execration in The kidney

Answer 18

Carnitine is filtered in the glomerulous & about 90% of carnitine is reabsorbed back to the Circulation
to Conserve it.

Question 19

What are the renal Causes of Carnitine deficiency?

Answer 19

1st⇒ Iry Carnitine deficiency due to a defect in the
plasma membrane Carnitine transporter in kidney& muscle.
The Lack of Plasma membrane Carnitine transporter results in urinary Loss of Carnitine, wasting & dec IC accumulation of Carnitine.

2nd ⇒ Preterm neonates are at risk of developing Carnitine deficiency due to impaired renal reabsorption of carnitine .
3rd⇒ Chronic renal failure results in Carnitine deficiency due to Dec Carnitine biosynthesis besides losing Carnitine
during hermodialysis.

2ry Acquired Carnitine deficiency ⇒ Can be seen in patients taking Anti Seizure dug as Valproate as it dec. Carnitine renal reabsorption.

Question 20

what are the Symptoms of carnitine deficiency?

Answer 20

hypoglycemia which is a consequence of impaired fatty acid
oxidation.
Muscle weakness
Heart affection

Question 21

How to Treat Carnitine deficiency?

Answer 21

L- Carnitine supplementation.

Question 22

Explain the role of the kidney in Ammonia Production & Control of acid-base balance.

Answer 22

One of the metabolic functions of the
kidney is the production of NH3 by the action of glutaminese & glutamate dehydrogenase enzyme.
N H3 produced Combines with H + ions to form NH 4 + ions which is then excreted. NH3+ H+→ N H4+
The produced ammonia plays an important role in the acid -base balance as it buffers H+
NH4 produced in the tubular human
accounts for 60% execretion of hydrogen ions associated with
high protein diet , Prolonged Starvation , . & overproduction of normal metabolic acids as Lactate , B- hydroxy butyrate & AcetoAcetate

Question 23

what are the Causes of
Acidosis & hypoglycemia
inpatients with renal insufficiency ?

Answer 23

Acidosis ⇒ due to dec. production
of NH3 So there is no enough Nits
to buffer excess hydrogen ions Leading
to systemic acidosis.
Hypoglycemia ⇒ dec. gluconeogenesis dec. functioning kidney mass + dec. Carnitine which dec ATP produced by fatty acid Oxidation which is required to supply energy for
gluconeogenesis.

Question 24

Mention the Endocrine function
of the kidney

Answer 24

Endocrine function of the kidneys involve the Synthesis & Secretion of the following:-
1⇒ renin involved in regulation of Bp
2 ⇒ Erythropoietin
3 ⇒ Activation of Vitamin D producing dihydroxy chole Calcefirol “ Calcitriol “ through its activation by alpha 1 hydroxylase Enzyme
4⇒ Synthesis of PGs which affect many processes of the kidney .

In addition to the degradation of certain hormones as insulin by insulinase enzyme & PTH

Question 25

Final urine is Characteristically ….- / -… ……
Specific gravity ⇒
PH ⇒
Volume ⇒

Answer 25

malodorous, clear & golden yellow
1003-1038 kg /m3
4.4 - 8
1.5-2L /day

Question 26

Mention Substances present in
Urine

Answer 26

Urine Contains Na,k +, Cl -, Creatinine,VMA “which is a product
of catecholamine
metabolism” , Ca,Urea &uric acid.
Healthy kidneys do notallow
the passage of significant
amounts of protein & glucose presence of glucose or protein
in urine is a pathological
finding.

Question 27

polyuria is ……
Anuria …
oligourea–

Answer 27

passage ofmore than 2L 1day

passage of Less than 0.5 L / day

Passage of < 0.1 L / day

Question 28

what are the 1ry components of renal glomerular membrane ?

Answer 28

3 proteins which are laminin,entactin,& Collagen type IV + glucoseaminoglycans,heparin or heparan sulfate

Question 29

how does the relatively thick basal Lamina of the glomerular regulate the passage of Large molecules as proteins across the glomerular membrane?

Answer 29

This Can be explained by two factors :
1 ⇒ The pores of theglomerular membrane are only Large enough to allow thepassage of molecules < 8 nm to pass Through.

2⇒ Although albumin is< 8nm
it is not allowed topass through the glomerular
membrane by the negative Charges of heparan sulfate & of certain sialic acid Containing gly coproteins present in the Lamina. these -we Charges repel
albumin & most plasma proteins which are negatively Charged at PH of the blood.

Question 30

what happens if’ the normal
Structure of the glomerulous is disrupted which can occur in certain types of glomerulonephritis “ Caused by Antibodies directed against Various components of glomerular membrane ?

Answer 30

This damage alters the pores & the amounts & disposition of _vely Charged macromolecules& relatively massive amounts of Albumin & other plasma proteins Can pass in Urine resulting in severe Albuminuria.