Water, sodium and potassium handling of the kidneys Flashcards
Kidney
Anatomic units:
Functional unit:
Anatomic units: medulla and cortex
Functional unit: nephron
Four Key Functions of the Kidneys
- Filtration
- Reabsorption - reabsorption is the transfer of water and solutes from the lumen to the blood
- Secretion
- Excretion - removes products of metabolism (urea, uric acid, and creatinine) in the urine and retain glucose, amino acids, and proteins
Liver and kidney are capable of gluconeogenesis
Liver:
Kidney:
Liver: 75%-80%
Kidney: 20%-25%
What are the preferential gluconeogenic precursors of kidney?
Glutamine and lactate
What are the key enzymes of gluconeogenesis?
Pyruvate carboxylase Phosphoenol Pyruvate carboxykinase (PEPCK) Fructose-1,6-bisphosphatase Glucose-6-phosphatase **mainly found at renal cortices
The kidneys produce three major hormones:
- Erythropoietin
- 1,25 dihydro-cholecalciferol
- 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
Norepinephrine increase Na reabsorption via
Directly:
Indirectly:
Directly: tubular Na/K ATPase
Indirectly: RAS
Na/K ATPase is controlled by what neurotransmitters?
Norepinephrine and Dopamine
The major reabsorptive tubule of the kidneys
The Proximal Convoluted Tubule
In the proximal convoluted tubule, sodium enters via the luminal side through what transport mechanism?
Na-H exchanger (NHE3) ion channels and via co transporters with: Glucose, Phosphate, and Amino Acids
In the proximal convoluted tubule,sodium leaves the cell going into the bloodstream via what transport mechanism?
Sodium bicarbonate co-transporter on the basolateral aspect of the membrane
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
Fanconi’s Syndrome
In the thin ascending limb of the loop of henle, Na move into the cell via what transport mechanism?
Na-KCl co transporter (NKCC2)
**This mechanism is inhibited by FUROSEMIDE
In the distal convoluted tubule, reabsorption of Na ions occurs thru what transport mechanism?
Na-Cl co transported (NCC)
** The Thiazide Diuretic works on this transporter
In the collecting duct, Na ions are reabsorbed by ____
Amiloride sensitive epithelial Na channels (ENaC)
What is the pharmacologic antagonist of aldosterone?
spironolactone
** Acts on the collecting duct
Angiotensinogen comes from ____ whereas Renin comes from _____
Liver; kidney
Renin activates angiotensinogen into ____
Angiotensin I
** Angiotensin I is further activated into Angiotensin II by ACE
Hormonal control
Increases Sodium reabsorption:
Decreases Sodium reabsorption:
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
Sodium Disorders
Sodium Depletion:
Sodium Excess:
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
Hyponatremia can be classified into three:
- hypovolemia: loss of both body sodium and body water.
- Euvolemia: no edema, normal number of sodium but higher total body water.
- 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
Management of Hyponatremia
Administer sodium intake:
Water restriction:
Administer sodium intake: True volume depletion, Diuretics, Adrenal insufficiency and Salt-losing tubolopathy
Water restriction: SIADH, Edematous states, renal failure and Primary polydypsia
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
Hypernatremic Dehydration
** Intracellular fluids shift into extracellular and intravascular spaces due to increased sodium concentration
Required for the active reabsorption of water needed in the body
Aquaporins
The location of the important Aquaporins of the Nephron:
Proximal tubule:
Descending limb:
Collecting ducts:
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
Inability of the kidney to respond to vasopressin leading to decreased incorporation of AQP2 in the membrane
Nephrogenic Diabetes Insipidus
Low levels of AQP2 and Polyuria are highly associated with _____
Nephrogenic Diabetes Insipidus, acquired Hypokalemia and Hypercalemia
Specific Tubulopathies Problems in the sodium chloride transport system: Problems in the Na-2Cl-K transporter: Recessive PHA 1 resulting into GRA: Synthase Deficiency:
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
What is the gold standard in measuring the GFR and is given exogenously?
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
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
Cystatin and NGAL
What biomarker for renal function is affected by food intake?
BUN
What biomarker for renal function is best used for adults?
Counahan Barratt
Mutation SLC5A2 gene encodes for SGLT 2 will result into what condition?
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%
Amino acids are almost completely reabsorbed in what part of the nephron?
Proximal tubule
**Plasma AA is freely filtered
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:
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
3 types of Na dependent Amino Acids
Neutral:
Acidic:
Basic:
Neutral: glycine, alanine, proline
Acidic: glutamate, aspartate
Basic: cysteine, arginine, ornithine and lysine
How many percent of the filtered phosphorus is reabsorbed in the proximal tubule
60%-70%
**A significant amount of filtered phosphorus is reabsorbed in distal segments of the nephron
Phosphate reabsorption is mediated by 2 Na-dependent PO4 co-transporter:
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
It is the major intracellular ion with 98% located in the cells
Potassium
85 - 95% of filtered K+ is reabsorbed by what segment of the nephron
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-
What is responsible for the fine tuning of potassium handling (responsible for adjustments in K+ excretion that occurs when dietary K+ varies)?
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
Increase of water passing thru the distal tubule and collecting duct will allow K+ secretion
REMEMBER
Tubular flow increases K+ secretion
Reabsorption of potassium in the PCT is mostly (a) active (b) passive
b. passive
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
REMEMBER
What are the three factors that regulate potassium secretion?
(1) Lumenal flow rate
(2) Aldosterone
(3) Presence of extracellular potassium
(4) Extracellular pH
(a) Acidosis (b) alkalosis increases potassium secretion
b. alkalosis
Stimulation of β2 adrenergic (epinephrine) receptors (a) increases (b) decreases potassium secretion
b. decreased
In patients with hyperkalemia, what is given to induce alkalosis to lower serum potassium?
Sodium bicarbonate
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)?
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.
