Flashcards in sodium handling Deck (37):
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Major determinants of ECF volume
sodium and associated anions such as chloride and bicarbonate
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Describe total body water distribution
The intracellular fluid (ICF) compartment contains 2/3 of TBW, and the extracellular fluid (ECF) compartments have the remaining 1/3 (1/4 is intravascular and 3/4 is in interstitial fluid)
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What determines water movement btw vascular and interstitial compartments
Capillaries are fenestrated so osmotic gradients usually do not form. Instead, starling forces (hydrostatic pressure and oncotic pressure from plasma protein conc) determine rate of water movement
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Effective arterial blood volume (EABV)
This is the volume of blood that is detected by volume sensors, located in the arterial side of the circulation. It is that amount of arterial blood volume required to adequately “fill” the capacity of arterial circulation.
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Components of the integrated homeostatic response to sodium
an afferent limb that detects changes in EABV and an efferent limb that regulates the rate of sodium excretion by the kidney
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List types of volume sens0rs in the afferent limb
1. Low-pressure baroreceptors. 2. High-pressure baroreceptors. 3. Intrarenal sensors. 4. Hepatic and central nervous system sensors.
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List types of low-pressure baroreceptors and how they work
• Cardiac atria receptors. • Left ventricular receptors. • Pulmonary vascular bed receptors. These sensors are located on the venous side of the circulation and protect the body against ECF volume expansion and contraction. Volume expansion > stimulates atrial wall stretch receptors > hypothalamic and medullary centers in brain decrease renal sympathetic nerve activity > loss of Na and water in kidney > reduction in ECF
• Cardiac atria receptors. • Left ventricular receptors. • Pulmonary vascular bed receptors. These sensors are located on the venous side of the circulation and protect the body against ECF volume expansion and contraction. Volume expansion > stimulates atrial wall stretch receptors > hypothalamic and medullary centers in brain decrease renal sympathetic nerve activity > loss of Na and water in kidney > reduction in ECF
• Cardiac atria receptors. • Left ventricular receptors. • Pulmonary vascular bed receptors. These sensors are located on the venous side of the circulation and protect the body against ECF volume expansion and contraction. Volume expansion > stimulates atrial wall stretch receptors > hypothalamic and medullary centers in brain decrease renal sympathetic nerve activity > loss of Na and water in kidney > reduction in ECF
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List types of high-pressure baroreceptors and how they work
• Carotid sinus body at the bifurcation of the carotid artery. • Aortic body in the aortic arch. Receptors on the arterial side that protect against volume contraction and expansion. Decreased EABV > receptors send signals to brain > increased renal sympathetic activity > anti-natriuresis and anti-diuresis. In severe volume loss, norepinephrine is also released which raises BP by increasing HR and vascular resistance.
• Carotid sinus body at the bifurcation of the carotid artery. • Aortic body in the aortic arch. Receptors on the arterial side that protect against volume contraction and expansion. Decreased EABV > receptors send signals to brain > increased renal sympathetic activity > anti-natriuresis and anti-diuresis. In severe volume loss, norepinephrine is also released which raises BP by increasing HR and vascular resistance.
• Carotid sinus body at the bifurcation of the carotid artery. • Aortic body in the aortic arch. Receptors on the arterial side that protect against volume contraction and expansion. Decreased EABV > receptors send signals to brain > increased renal sympathetic activity > anti-natriuresis and anti-diuresis. In severe volume loss, norepinephrine is also released which raises BP by increasing HR and vascular resistance.
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Describe where intrarenal sensors are located and how they work
Intrarenal sensors are formed by the renal juxtaglomerular apparatus (JGA) that releases renin> angiotensin > angiotensin II > aldosterone > increased Na reabsorption
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List factors that influence effector function in kidney
1. Glomerular filtration. 2. Physical factors at the level of the proximal tubule. 3. Humoral effector mechanisms. 4. Renal sympathetic nerves
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What determines glomerular filtration rate
hydrostatic and oncotic pressure of glomerular capillary and tubules.
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Explain three processes that maintain GFR relatively constant
Renal autoregulation: contraction/dilation of afferent arteriole in response to intravascular pressure maintains renal blood flow and GFR constant. Tubuloglomerular feedback: increased distal delivery of sodium chloride to the macula densa (part of the JGA) increases afferent arteriolar tone and returns the RBF and GFR towards normal values. Glomerulo-tubular balance : changes in GFR automatically induce a proportional change in the rate of proximal tubular sodium reabsorption to maintain the fractional excretion of sodium.
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Describe humoral effector mechanisms
Two groups of hormones: 1) increase sodium reabsorption: angiotensin II, aldosterone, ADH and catecholamines. 2) Decrease sodium reabsorption: prostaglandins, bradykinin, dopamine and atrial natriuretic peptide.
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Renal sympathetic nerve functions in effector mechanisms
The sympathetic nervous system innervates the afferent and efferent arterioles of the glomerulus. In volume contraction, SNS is stimulated has anti-natriuretic effect plus enhances release of renin from JGA
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Mechanism of sodium reabsorption in proximal tubule
Reabsorbs about 60% of the glomerular filtrate, including the sodium. Passive movement of Na occurs from the lumen into the cell, down its conc gradient. Na conc in the cell is low due to a Na/K pump at the basolateral side of cell which pumps Na into blood. Active entry of sodium into the cell from the lumen is via Cl, phosphate, glucose and amino acid sodium-dependent co-transport, or Na/H antiporter.
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Mechanism of sodium reabsorption in loop of Henle
30% of filtered sodium reabsorbed in thick ascending limb. Impermeable to water but highly permeable to Na. Na is reabsorbed from lumen into cell by Na/K/2Cl co transporter (active), making tubular fluid more dilute
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Mechanism of sodium reabsorption in Distal convoluted tubule
Na enters cell via Na channel (which attracts Cl ions paracellularly), Na/Cl co-transporter and Na/H antiporter
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Mechanism of sodium reabsorption in cortical collecting duct
2 cell types in collecting duct are principal cells and intercalated cells. In principal cell, sodium enters from the tubule lumen in exchange for potassium via channels. Intercalated cells are involved in H ion and bicarb secretion
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2 mechanisms for renal loss of ECF sodium and water
1) Failure of effector mechanism: solute diuresis, glucosuria, diuretics, adrenal insufficiency, aldosterone deficiency, mutations in sodium transporters . 2) Intrinsic renal disease: non-oliguric acute renal failure, post-obstructive diuresis, salt-wasting nephropathy, medullary cystic disease, tubulo-intersititial disease
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Bartters syndrome
Mutation in Na/K/2Cl co-transporter in the Thick Ascending LH. This syndrome is characterized by hypokalemia, hypomagnesemia, metabolic alkalosis, high plasma renin and aldosterone levels, increased calcium excretion, and normal blood pressure.
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Gitelmans syndrome
mutation in NaCl co-transporter in the distal tubule. It is characterized by hypokalemia, hypomagnesemia, metabolic alkalosis, and reduced urinary excretion of calcium.
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Describe cardiovascular response to ECF volume contraction
Baroreceptors detect volume contraction and attempt to maintain blood pressure by: • Increased sympathetic activity which causes increased heart rate, cardiac inotropic function, and systemic vascular resistance. • Increased secretion of vasoconstrictor hormones such as angiotensin II, AVP, endothelin
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Describe renal response to ECF volume contraction
Attempts to replenish lost fluids, conserve salt and water: • Decreased GFR • Activation of the renal sympathetic nerves decreases GFR • Decreased hydrostatic pressure and increased oncotic pressure in the peritubular capillaries • Stimulation of renin-angiotensin-aldosterone system.• Increased secretion of ADH • Inhibited secretion of atrial natriuretic peptide
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Clinical manifestations of ECF volume contraction
Thirst, postural dizziness, Weakness, palpitation, Decrease urinary output, confusion, Weight changes, Orthostatic blood pressure, tachycardia, hypotension, Decreased elasticity or turgor of the skin, Dry mucous membranes
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Serum manifestations of volume contraction: BUN/Cr ratio, metabolic alkalosis/acidosis, hematocrit, serum ablumin
• Increased BUN: plasma creatinine ratio (urea passively follows Na reabsorption)• Metabolic alkalosis during upper GI loss of fluid/acids. • Metabolic acidosis during lower GI loss of fluid/bicarb. • Increased hematocrit and serum albumin because of hemoconcentration.
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Urinary manifestations of volume contraction: Na, specific gravity, osmolality
Urinary Na is low (kidney is reabsorbing it), except in ATN where Na is high due to injured tubules that cant reabsorb it. Urine specific gravity and osmolality are high b/c kidney reabsorbs Na and water
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Treatment of volume contraction
Expansion of ECF volume: Blood, albumin and dextran solutions containing large molecules preferentially expand the intravascular volume. Isotonic normal saline (which is comprised of 0.9% NaCl or 154 mEq/L of NaCl) preferentially expands the ECF volume (ie. 20% remains intravascular and 80% in interstitium)
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Causes of extravascular volume expansion
1) disturbed starling forces 2) primary hormone excess or 3) primary renal sodium retention
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Describe how disturbances in Starling forces leads to volume expansion
Decreased capillary oncotic pressure or increased capillary hydrostatic pressure initiates edema. Baroreceptors perceive reduced effective arterial circulating volume which stimulates kidneys to retain sodium and water. This is seen in CHF, nephrotic syndroe and cirrhosis
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Describe renal sodium and water retention in heart failure
Decreased cardiac output > activation of arterial baroreceptors > SNS stimulation, RAAS activation and non-osmotic ADH stimulation > renal water, sodium retention and increased peripheral and renal arterial vascular resistance
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Nephrotic syndrome and water/Na retention
Albumin is lost in urine, causing hypoalbuminemia and a drop in capillary oncotic pressure. This drives fluids from vascular space into intersitium, causing a fall in effective arterial blood volume
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mechanism for Na and water retention in cirrhosis
Intrahepatic hypertension, portal hypertension, splanchnic vasodilation, and hypoalbuminemia characterize cirrhosis and lead to the underfilling of the arterial circulation.this leads to increased capillary hydrostatic pressure and decreased capillary oncotic pressure, with loss of fluids into interstitial compartment. Decreased EABV activates renal effectors causing Na dna water retention.
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Therapy of volume expansion
Treat underlying condition, salt restriction and diuretics. Avoid drugs such as NSAIDs which predispose to salt retention
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Diuretics acting at proximal tubule
Acetazolamide- blocks carbonic anhydrase causing wastage of bicarbonate. Weak
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Diuretics acting at loop of Henle
furosemide, bumetanide, and torsemide. These agents work by inhibiting the coupled entry of sodium, potassium, and chloride across the apical membrane in the thick ascending limb of the loop of Henle (at the Na/2Cl/K co-transporter).
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Diuretics acting at distal convoluted tubule
Thiazides inhibit the sodium/chloride transporter and block sodium entry across the apical membrane into distal tubular cells
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