DISORDERS OF SODIUM AND WATER METABOLISM Flashcards
What is the usual daily dietary intake of sodium?
2-10g
Where along the nephron does the majority of the sodium reabsorption take place?
65% in the proximal convoluted tubule
25% in the thick ascending limb of the loop of Henle
What is sodium exchanged for in the proximal convoluted tubule?
Potassium
Hydrogen ions
In the tubules of the nephron, how is a sodium gradient created between the lumen and the basal membrane cells?
Na/K ATPase on the interstitium side of the basal membrane
In the early proximal convoluted tubule of the nephron, what is the exchanger responsible for sodium reabsorption from the filtrate into the basal membrane cell?
Na/H exchanger (NHE3)
In the early proximal convoluted tubule of the nephron, what is reabsorbed by co-transporters as a result of the sodium concentration gradient?
Glucose
Amino acids
Organic molecules
HCO3- ions
In the proximal convoluted tubule of the nephron, how are chloride ions reabsorbed?
H+ ions are exchanged for Na+ ions on the lumen side of the basal membrane cell. This increase in H+ ions in the lumen draws HCO3- out into the lumen, via a Cl-/HCO3- exchanger (AE1). Cl- is also able to pass through the basal membrane between the cells due to the negative charge of the filtrate as the Cl is allowed to concentrate.
What is the key transport molecule of the thick ascending limb of the loop of Henle?
NKCC2 transporter which transports a Na+ ion, 2 Cl- ions and a K+ ion from the lumen into the basal cell. This is driven by the Na/K ATPase. The potassium is allowed to reenter the lumen via ROMK channels.
What percentage of sodium ions are reabsorbed in the distal convoluted tubule of the nephron?
5%
What is the co-transporter responsible for the reabsorption of sodium in the distal convoluted tubule?
NCC sodium chloride cotransporter.
What are the two characteristic cell types in the collecting duct of the nephron?
Principal cells
Type B intercalated cells
How is sodium reabsorbed in the collecting ducts?
Na/K ATPase at the interstitial side of the basal membrane causes a concentration gradient that allows sodium to flow freely out of the lumen through sodium channels called ENaC (epithelial sodium channels).
What hormone increases the rate of the NHE3 exchanger in the early proximal convoluted tubule which is responsible for exchanging Na and H ions?
Angiotensin II
What diuretic inhibits the NKCC2 co-transporter which reabsorbs Na, K and 2 Cl ions in the thick ascending limb of the loop of Henle?
Furosemide (loop diuretics)
What diuretic inhibits the NCC (sodium chloride co-transporter) in the distal convoluted tubule?
Thiazide diuretics
What diuretic inhibits the ENaC (epithelial sodium channel) in the collecting duct of the nephron?
Amiloride
What is the hormone that inhibits the ENaC (epithelial sodium channel) in the collecting duct of the nephron?
Atrial natriuretic peptide (ANP)
What is the hormone that promotes transcription of the ENaC (epithelial sodium channel) in the collecting duct of the nephron?
Aldosterone
What is the hormone that promotes transcription of the Na/K ATPase in the collecting duct of the nephron?
Aldosterone
What is the normal osmolality of the blood?
285-295 mosmol/kg
What is the maximum urine osmolality as it leaves the collecting ducts?
1400 mosmol/kg
How many milliosmols of waste products are excreted by the kidney per day?
600 mosmol
What parts of the nephron are water permeable?
Proximal tubule
Descending limb of the loop of Henle
Collecting duct
How is water reabsorbed in the proximal tubule of the nephron?
Osmosis following NaCl
What is the osmolality of the filtrate by the time it reaches the beginning of the collecting duct?
80 mosmol/kg
What is the hormone responsible for controlling water reabsorption in the collecting ducts?
ADH
Is the medulla of the kidney hypo- or hyper-tonic?
Hypertonic
How does ADH increase water reabsorption in the collecting ducts of the nephron?
Aquaporin proteins are inserted into the apical membrane of the basal cells
Stimulates urea reabsorption which increases osmosis.
What are the baroreceptors responsible for detecting when blood volume becomes too low?
High-pressure arterial stretch receptors
What are the baroreceptors responsible for detecting when blood volume becomes too high?
Low-pressure venous stretch receptors
What is the direct stimulus for the release of renin?
A drop in the amount of NaCl delivered to the macula densa.
What are the functions of angiotensin II?
Reabsorption of sodium in proximal tubules Thirst Aldosterone production ADH release Renal and systemic vasoconstriction
Where in the kidney does angiotensin II have its effect on sodium reabsorption?
Early proximal tubule - increases NHE3 (sodium hydrogen exchanger)
Where in the kidney do thiazides have their effect on sodium reabsorption?
Distal tubule - inhibits NCC (sodium chloride co-transporter)
Where in the kidney does furosemide have its effect on sodium reabsorption?
Thick ascending limb of the loop of Henle - inhibits NKCC2 (sodium, potassium and chloride co-transporter)
Where in the kidney does amiloride have its effect on sodium reabsorption?
Collecting ducts - inhibits ENaC (epithelial sodium channel)
Where in the kidney does atrial natriuretic peptide have its effect on sodium reabsorption?
Collecting ducts - inhibits ENaC (epithelial sodium channel)
Also inhibits aldosterone release and renin production.
Increases GFR by dilating afferent arterioles.
Where in the kidney does aldosterone have its effect on sodium reabsorption?
Collecting ducts - promotes transcription of ENaC (epithelial sodium channels) and Na/K ATPase.
Where in the kidney does dopamine have its effect on sodium reabsorption?
Proximal tubule - inhibits the NHE3 (sodium hydrogen exchanger)
Where in the kidney do alpha-adrenergic agonists have their effect on sodium reabsorption?
Proximal tubule - enhance NHE3 (sodium hydrogen exchanger)
What are the different types of hypernatraemia?
Hypervolemic
Hypovolemic
Euvolemic
What are the causes of hypervolemic hypernatraemia?
Excessive IV sodium administration (eg sodium bicarbonate)
Excessive salt ingestion
Mineralocorticoid excess (Cushing’s syndrome or hyperaldosteronism)
What are the causes of hypovolemic hypernatraemia?
Dehydration
Sweating
Severely watery diarrhoea
What are the causes of euvolemic hypernatraemia?
Diabetes insipidus
What are the clinical features of hypernatraemia?
Hyperosmolality causes brain cells to shrink as water leaves by osmosis.
Early signs: Increased excitability Increased irritability Muscle twitches and muscle weakness Brisk reflexes Spasticity High pitch cyring in infants
Late signs:
Tachypnoea
Seizures
Coma
How would you manage a symptomatic patient found to be hypernatraemic?
Correction of water deficits if fluid deprived (either oral or IV dextrose 5%)
Prevention of ongoing losses - desmopressin (used in treatment of diabetes insipidus)
Withdraw causative agent (eg sodium infusion)
Treat Cushing’s syndrome - metyrapone, surgery, radiotherapy
Treat hyperaldosteronism - spiranolactone, surgery
Regular checks of sodium to make sure that levels are not being corrected too quickly
Why must you make sure that you do not correct hypernatraemia too quickly?
Because the body and brain adapt to high levels of sodium so rapid correction can lead to acute cerebral oedema.
How quickly should sodium levels in hypernatraemia be corrected?
No more than 8-10 mmol/L per 24 hours (0.5mEq/hour)
What are the different types of hyponatraemia?
Normosmolar hyponatraemia
Hypervolemic hyposmolar hyponatraemia
Euvolemic hyposmolar hyponatraemia
Hypovolemic hyposmolar hyponatraemia
What are the causes of normosmolar hyponatraemia?
Diabetes mellitus - glucose keeps the osmolality normal
Pseudohyponatraemia
What is pseudohyponatraemia?
Excess protein or lipids in the blood. There is normal amount of sodium in each litre of plasma water, but the total amount of plasma is reduced because the volume is made up of excess protein or lipid.
What are the causes of hypervolemic hyposmolar hyponatraemia?
Renal failure
Heart failure
Liver failure
Too much IV dextrose 5% (especially in renal failure patients)
What are the causes of euvolemic hyposmolar hyponatraemia?
Syndrome of inappropriate ADH release (SIADH)
Hypothyroidism
Drugs that can lead to SIADH
Psychogenic polydipsia
What are the medications that can cause SIADH?
Amiodarone Amitriptyline (Elavil) Barbiturates Carbamazepine (Tegretol) Chlorpromazine (Thorazine) Chlorpropamide Clofibrate Cyclophosphamide Morphine Sulfate and other Opioids NSAIDs Selective Serotonin Reuptake Inhibitors (SSRIs) Theophylline Thiazide Diuretics (e.g. Hydrochlorothiazide) Tolbutamide Vincristine
Why does SIADH normally cause euvolemic hyponatraemia not hypervolemic hyponatraemia?
The kidney responds to the initial increase in volume by excreting more sodium and hence water leaves with it. This causes normal volume but reduced sodium.
What are the causes of hypovolemic hyposmolar hyponatraemia?
ADH response to vomiting and diarrhoea
Severe burns
Diuretics
Addison’s disease (mineralocorticoid insufficiency)
What are the clinical features of hyponatraemia?
Causes brain oedema
Early: Often asymptomatic Vomiting Diarrhoea Headache Lethargy Dizziness
Late signs: Seizure Coma Confusion Ataxia Respiratory depression
How would you manage a symptomatic patient found to be hyponatraemic?
Treat underlying cause
Correction of volume and salt using 0.9% saline
ADH antagonists (vaptans)
Stop dextrose infusion
How does congestive heart failure lead to the kidney retaining more sodium and water, resulting in a state of hypervolemia and oedema?
Reduced cardiac output leads to reduction in blood pressure which is perceived as hypovolaemia. This causes enhanced sympathetic and catecholamine activity as well as enhanced RAAS activity and excess ADH.
How does liver cirrhosis lead to the kidney retaining more sodium and water, resulting in a state of hypervolemia and oedema?
Raised NO levels or a failure of the diseased liver to degrade other vasoactive substances leads to widespread vasodilation which reduces BP and perceived hypovolaemia.
Ascites is also caused by portal hypertension and low albumin will decrease fluid reabsorption from the interstitium in the capillary bed.
What is the effect of activation of the sympathetic nervous system on the kidney?
Promotes sodium reabsorption from the proximal tubules and reduces renal blood flow through by renal vasoconstriction.