Water, sodium and potassium handling of the kidneys

Question 1

Kidney
Anatomic units:
Functional unit:

Answer 1

Anatomic units: medulla and cortex

Functional unit: nephron

Question 2

Four Key Functions of the Kidneys

Answer 2

1. Filtration
2. Reabsorption - reabsorption is the transfer of water and solutes from the lumen to the blood
3. Secretion
4. Excretion - removes products of metabolism (urea, uric acid, and creatinine) in the urine and retain glucose, amino acids, and proteins

Question 3

Liver and kidney are capable of gluconeogenesis
Liver:
Kidney:

Answer 3

Liver: 75%-80%
Kidney: 20%-25%

Question 4

What are the preferential gluconeogenic precursors of kidney?

Answer 4

Glutamine and lactate

Question 5

What are the key enzymes of gluconeogenesis?

Answer 5

Pyruvate carboxylase 
Phosphoenol Pyruvate carboxykinase (PEPCK) 
Fructose-1,6-bisphosphatase 
Glucose-6-phosphatase 
**mainly found at renal cortices

Question 6

The kidneys produce three major hormones:

Answer 6

1. Erythropoietin
2. 1,25 dihydro-cholecalciferol
3. Renin
   * * End stage renal disease can thus cause: severe anemia, stunting for age, and difficulty of blood pressure management due to the inadequacy of the above hormones

Question 7

Norepinephrine increase Na reabsorption via
Directly:
Indirectly:

Answer 7

Directly: tubular Na/K ATPase
Indirectly: RAS

Question 8

Na/K ATPase is controlled by what neurotransmitters?

Answer 8

Norepinephrine and Dopamine

Question 9

The major reabsorptive tubule of the kidneys

Answer 9

The Proximal Convoluted Tubule

Question 10

In the proximal convoluted tubule, sodium enters via the luminal side through what transport mechanism?

Answer 10

Na-H exchanger (NHE3) ion channels and via co transporters with: Glucose, Phosphate, and Amino Acids

Question 11

In the proximal convoluted tubule,sodium leaves the cell going into the bloodstream via what transport mechanism?

Answer 11

Sodium bicarbonate co-transporter on the basolateral aspect of the membrane

Question 12

IN THE CLINIC
A condition wherein the proximal convoluted tubules ceases to work thus as a manifestation, the urine of the patient should contain high amounts of Amino Acids, Glucose, and Sodium

Answer 12

Fanconi’s Syndrome

Question 13

In the thin ascending limb of the loop of henle, Na move into the cell via what transport mechanism?

Answer 13

Na-KCl co transporter (NKCC2)

**This mechanism is inhibited by FUROSEMIDE

Question 14

In the distal convoluted tubule, reabsorption of Na ions occurs thru what transport mechanism?

Answer 14

Na-Cl co transported (NCC)

** The Thiazide Diuretic works on this transporter

Question 15

In the collecting duct, Na ions are reabsorbed by ____

Answer 15

Amiloride sensitive epithelial Na channels (ENaC)

Question 16

What is the pharmacologic antagonist of aldosterone?

Answer 16

spironolactone

** Acts on the collecting duct

Question 17

Angiotensinogen comes from ____ whereas Renin comes from _____

Answer 17

Liver; kidney

Question 18

Renin activates angiotensinogen into ____

Answer 18

Angiotensin I

** Angiotensin I is further activated into Angiotensin II by ACE

Question 19

Hormonal control
Increases Sodium reabsorption:
Decreases Sodium reabsorption:

Answer 19

Increases Sodium reabsorption: Cortisol, Estrogen, Growth Hormone, and Insulin
Decreases Sodium reabsorption: Glucagon, Progesterone, Parathyroid Hormone, Prostaglandins and kinins
**Natriuretic Hormones increases GFR and GFR decreases Na reabsorption

Question 20

Sodium Disorders
Sodium Depletion:
Sodium Excess:

Answer 20

Sodium Depletion: actual losses of sodium in the GIT by vomiting, diarrhea, fistula and burns in the skin
Sodium Excess: seen in patients with cirrhosis nephritic syndrome, and congestive heart failure

Question 21

Hyponatremia can be classified into three:

Answer 21

1. hypovolemia: loss of both body sodium and body water.
2. Euvolemia: no edema, normal number of sodium but higher total body water.
3. Hypervolemia: both total body water and total body sodium content increases.
   * * In cases of low sodium content, take in more sodium
   * *In cases normal sodium content but high total body water, the management is to restrict fluid intake

Question 22

Management of Hyponatremia
Administer sodium intake:
Water restriction:

Answer 22

Administer sodium intake: True volume depletion, Diuretics, Adrenal insufficiency and Salt-losing tubolopathy
Water restriction: SIADH, Edematous states, renal failure and Primary polydypsia

Question 23

A very rare occurence that is caused by an excessive intake of ORS or Na-Bicarbonate tablet, or if iatrogenically NSS IV fluids were given. Seen in neonates and infants, bedridden children who have no access to water or thirst mechanism is not intact

Answer 23

Hypernatremic Dehydration

** Intracellular fluids shift into extracellular and intravascular spaces due to increased sodium concentration

Question 24

Required for the active reabsorption of water needed in the body

Answer 24

Aquaporins

Question 25

The location of the important Aquaporins of the Nephron: Proximal tubule: Descending limb: Collecting ducts:

Answer 25

Proximal tubule: AQP 1, 7, 8 Descending limb: AQP 1 Collecting ducts: AQP 2, 3, 4, 6, 8 ** The ascending limb has no aquaporins; most are found in the proximal tubule and the collecting duct

Question 26

Inability of the kidney to respond to vasopressin leading to decreased incorporation of AQP2 in the membrane

Answer 26

Nephrogenic Diabetes Insipidus

Question 27

Low levels of AQP2 and Polyuria are highly associated with _____

Answer 27

Nephrogenic Diabetes Insipidus, acquired Hypokalemia and Hypercalemia

Question 28

``` Specific Tubulopathies Problems in the sodium chloride transport system: Problems in the Na-2Cl-K transporter: Recessive PHA 1 resulting into GRA: Synthase Deficiency: ```

Answer 28

Problems in the sodium chloride transport system: Gitelman syndrome (associated with hypokalemia) Problems in the Na-2Cl-K transporter: Bartter syndrome (associated with hypokalemia) Recessive PHA 1 resulting into GRA: Aldosterone Synthase Deficiency: Liddle Syndrome

Question 29

What is the gold standard in measuring the GFR and is given exogenously?

Answer 29

Inulin * *It is not produced by the body but rather is given to the patient and filtered by the kidney * *creatinine can also be used as a measurement of GFR but the problem is a slight amount is being secreted by the body

Question 30

A better alternative for creatinine in measuring GFR because less amount is secreted by the body and can detect renal failure at an earlier stage

Answer 30

Cystatin and NGAL

Question 31

What biomarker for renal function is affected by food intake?

Answer 31

BUN

Question 32

What biomarker for renal function is best used for adults?

Answer 32

Counahan Barratt

Question 33

Mutation SLC5A2 gene encodes for SGLT 2 will result into what condition?

Answer 33

Familial renal glucosuria * *Difficulty in controlling the release of glucose in the urine * *SGLT 1: high affinity, low capacity transporter * *SGLT 2: low affinity, high capacity transporter; reabsorbs 90%

Question 34

Amino acids are almost completely reabsorbed in what part of the nephron?

Answer 34

Proximal tubule | **Plasma AA is freely filtered

Question 35

Amino Acid reabsorption at the renal proximal tubules is mediated by the specialized amino acid transport systems situated on the apical membrane and basolateral membrane of the epithelial cells. Transport mechanism of acidic AA: Transport mechanism of neutral AA: Cysteine and basic AA:

Answer 35

Transport mechanism of acidic AA: reabsorbed by the apical membrane via XA,G glutamate transporter Transport mechanism of neutral AA: reabsorbed by the apical membrane via Na+ dependent transport system B0 Cysteine and basic AA: leave the cells via the basolateral membrane exchanger system y+L

Question 36

3 types of Na dependent Amino Acids Neutral: Acidic: Basic:

Answer 36

Neutral: glycine, alanine, proline Acidic: glutamate, aspartate Basic: cysteine, arginine, ornithine and lysine

Question 37

How many percent of the filtered phosphorus is reabsorbed in the proximal tubule

Answer 37

60%-70% | **A significant amount of filtered phosphorus is reabsorbed in distal segments of the nephron

Question 38

Phosphate reabsorption is mediated by 2 Na-dependent PO4 co-transporter:

Answer 38

NaPi-IIa and NaPi-IIc * *NaPi-IIa is electrogenic because 1 divelent of PI ion is coupled with 3 Na * * NaPi-IIc is electroneutral and is coupled with 2 Na

Question 39

It is the major intracellular ion with 98% located in the cells

Answer 39

Potassium

Question 40

85 - 95% of filtered K+ is reabsorbed by what segment of the nephron

Answer 40

Proximal tubule and Loop of Henle * *65 % of filtered K+ is reabsorbed in the proximal tubule * * 20 – 30% is reabsorbed by the Loop of Henle especially in the thick ascending limb where it is co-transported along with Na+ and Cl-

Question 41

What is responsible for the fine tuning of potassium handling (responsible for adjustments in K+ excretion that occurs when dietary K+ varies)?

Answer 41

Distal tubule and collecting duct * *Principal cells carry potassium secretion * *Intercalated cells carry potassium reabsorption * *A high aldosterone level which increase reabsorption of Na+ will promote K+ excretion

Question 42

Increase of water passing thru the distal tubule and collecting duct will allow K+ secretion

Answer 42

**REMEMBER**

Question 43

Tubular flow increases K+ secretion | Reabsorption of potassium in the PCT is mostly (a) active (b) passive

Answer 43

b. passive

Question 44

Along the descending limb of the loop of henle, K is secreted into the tubule lumen from the interstitium. Along the thick ascending limb, K is reabsorbed by the Na‐K-Cl cotransport. In the loop, there is net reabsorption of 25% of the filtered K. Along the distal tubule and the collecting ducts, there is net secretion of K which is stimulated by aldosterone levels. Finally, in the CD, K secretion is by the principal cells and K reabsorption is by the alpha intercalated cells via a Luminal H-K-ATPase

Answer 44

**REMEMBER**

Question 45

What are the three factors that regulate potassium secretion?

Answer 45

(1) Lumenal flow rate (2) Aldosterone (3) Presence of extracellular potassium (4) Extracellular pH

Question 46

(a) Acidosis (b) alkalosis increases potassium secretion

Answer 46

b. alkalosis

Question 47

Stimulation of β2 adrenergic (epinephrine) receptors (a) increases (b) decreases potassium secretion

Answer 47

b. decreased

Question 48

In patients with hyperkalemia, what is given to induce alkalosis to lower serum potassium?

Answer 48

Sodium bicarbonate

Question 49

HOW to evaluate HYPOKALEMIA Is there leukocytosis present? Is there evidence of elevated aldosterone use of insulin, theophylline or adrenergic agent? Is there evidence of fluid loss (GIT or skin)?

Answer 49

Is there leukocytosis present? If yes, pseudohypokalemia (potassium going inside ICF) Is there evidence of elevated aldosterone use of insulin, theophylline or adrenergic agent? If yes, redistribution is happening Is there evidence of fluid loss (GIT or skin)? If yes, non-renal potassium loss ** The ECG change most specific for hypokalemia is the decreased amplitude of the T wave.