Hemodynamics and Electrolytes Flashcards
Kidney Function
Regulation of fluid and electrolyte balance.
Regulation of plasma osmolarity.
Elimination of metabolic waste products.
Production of hormones (erythropoietin, renin)
Metabolism: ammonia genesis and gluconeogenesis.
Metabolic waste products eliminated by kidney
Urea, creatinine, urobilirubin, uric acid, and foreign substances (drug).
Hormones made/converted in kidneys
erythropoietin, renin
Vitamin D converted to active form for calcium homeostasis.
erythropoietin
Stimulates RBC production in bone marrow. Made in kidneys.
Renin
A proteolytic enzyme, made in the kidney and secreted into the blood. It converts Angiotensinogen to angiotensin 1, which is then converted to angiotensin 2 by angiotensin converting enzyme.
Renin-angiotensin system
Critical for fluid/electrolyte homeostasis and longterm blood pressure regulation.
Kidney blood supply
Renal arteries, 1L/min
Glomerulus
Part of nephron. Blood enters from afferent arteriole and exits via efferent arterioles. Glomerulus filters blood. It has a basement membrane that filters blood cells, proteins, and most macromolecules out of the filtrate.
Macula Densa
And area of the nephron where the distal convoluted tubule return to the glomeruli, making contact with the afferent arterioles. At this site are cells called Macula Densa. The Macula Densa cells sense tubular flow, and regulate GFR.
Proteinuria
Few proteins are filtered through the glomerulus due to membrane tightness and charge. However, those that are filtered cannot be reabsorbed and will appear in urine; proteinuria.
Glomerular filtration rate (GFR)
GFR is the standard measurement for kidney function. It is the amount of plasma that is filtered across all glomeruli in the kidneys. 100-125 mL/min is normal.
Plasma creatinine is used to clinically estimate the GFR, because it is produced at a near constant rate. When GFR is low, less creatine is filtered and serum creatine levels are high.
RAAS
The renin–angiotensin-aldosterone system is a hormone system that is involved in the regulation of renal blood flow, plasma electrolyte concentration and arterial blood pressure.
RAAS is activated by low renal blood flow (RBF). The juxtaglomerular cells in the kidneys convert prorenin into renin, which is then secreted directly into the circulation. Plasma renin then cuts a plasma protein known as angiotensinogen. The short peptide is known as angiotensin I is then converted, by the removal of 2 amino acids, to form angiotensin II, by the enzyme angiotensin-converting enzyme (ACE) found in the endothelial cells of the capillaries throughout the body. Angiotensin II causes arterioles to constrict, resulting in increased arterial blood pressure. Angiotensin II also stimulates the secretion of the hormone aldosterone from the adrenal cortex. Aldosterone causes the tubular epithelial cells of the kidneys to increase the reabsorption of sodium ions from the tubular fluid back into the blood, while at the same time causing them to excrete potassium ions into the tubular fluid which will become urine.
If the RAAS is abnormally active, blood pressure will be too high.
Angiotensin 2
Angiotensin 2 exerts direct and indirect effects on the GFR. It is a vasoconstrictor, and in the kidneys it acts directly on renal arteries and aff/efferent arterioles, increasing resistance and decreasing GFR.
ANP (atrial natriuretic peptide)
ANP is released by cardiac myocytes in response to stretch at high blood volume. To regulate GFR, ANP dilates the afferent arteriole and constricts the efferent arteriole, increasing GFR. This increases sodium and water excretion, thereby decreasing blood volume.
Sympathetic nerves and chatecholamines
Sympathetic nerves and chatecholamine secretion (norepinephrine and epinephrine) are stimulated in response to low blood pressure and cause vasoconstriction of the renal arteries and arterioles, thus decreasing GFR. This systemic regulation can be counterbalanced by intrarenal systems, if necessary, to maintain RBF and GFR while the sympathetic system is acting to increase blood pressure.
Intrarenal Prostaglandins
Intrarenal Prostaglandins are vasodilators and act to counteract RAAS vasoconstriction. They act at the level of renal arterioles. NSAIDs will block Infrarenal Prostaglandins, restricting the compensatory vasodilation.
Bowman’s capsule
Bowman’s capsule is a cup-like sack at the beginning of the tubular component of a nephron in the kidney that performs the first step in the filtration of blood to form urine. Glomerular filtrate from blood is filtered by the glomerulus and collected in the Bowman’s capsule and further processed along the nephron to form urine.
Reabsorption
The process by which the nephrons reabsorb the majority of glucose, ions and water from the filtrate. Mostly occurs in the proximal tubule. The distal site do fine-tuning.
Proximal tubule (PT)
The majority of reabsorption occurs here. It is composed of three segments S1-3, each going deeper into the cortex/medulla. Mitochondria in the PT cells decreases as it the PT progresses, consistent with the amount of ATP required for active transport.
Absorbs 100% of glucose and AAs.
65-80% of NA, K, Cl, Phosphate, and H20.
Blood SOKI
Blood side: Sodium out, potassium in.
Requires ATP.
PT; S1, S2 (convoluted)
On the blood side (basolateral) of the PT cell, Na/K pump uses ATP to establish a electrochemical gradient. This gradient allows Na+ to be cotransported into the cell with other X molecules, such as glucose, amino acids, phosphate. Also on the basolateral side are Na/H anti-porters, which transport H into the lumen (across apical side). On the basolateral side, X molecules and bicarbonate diffuse into blood.
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PT; S3 (proximal straight tubule)
Na/K pump continues maintaining the electrochemical gradient, although to a lesser extent. It also crosses paracellularly with Cl-.
Na/H anti porters continue reabsorbing Na and secreting H into the lumen. Because water has been reabsorbed, solutes remaining in the lumen are of a higher concentration. Chloride crosses the lumen (apical) in exchange with anions (Oh-, SO4-, etc). Cl- then crosses the basolateral membrane with a K/Cl symporter.
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Thin descending loop of henle:
This segment is impermeable to Na and most other solutes but is permeable to water. Water is reabsorbed through channels, which results in tubular fluid being more concentrated at the loop of Henle.
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Thick ascending loop of Henle:
This segment is opposite to the thin descending loop in that it is impermeable to water but transports the concentrated ions into the lumen, thus diluting the tubular fluid. Na/K pump continues. The gradient allows Na/2Cl/K to symport across apical border. K diffuses through both membranes, Cl, through basolateral. And Na/H antiporter continues the the secretion of H.
Paracellular movement of ions, from the tubule to the blood, also occurs; Ca2+, Mg2+, Na+, K+.
Ionic cotransporters here are the target for loop diuretics, such as furosemide and bumetanide.
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Distal tubule
The distal tubule has apical Na/Cl- symporters.
Apical side also has Na and K channels that can be stimulated by aldosterone, resulting in greater Na and water reabsorption and greater K secretion.
Collecting duct
Like the distal tubule, the collecting duct has Na and K channels that can be stimulated by aldosterone, resulting in greater Na and water reabsorption and greater K secretion.
Glucose reabsorption
Glucose is reabsorbed in the PT by insulin dependent sodium-glucose transporters. It occurs via SGLT1 in segments 1 and 2, but by SGLT2 in segment 3. Its exits the basolateral membrane by GLUT2 facilitated transport.
Glucosuria
Extent of reabsorption depends on the availability of transporters. If glucose levels are excessively high, transporters may be saturated. Glucose will not all be reabsorbed and will be excreted in the urine (glycosuria)..
Bicarbonate handeling
All bicarbonate is reabsorbed, as required for acid base homeostasis.
In the lumen, brush border carbonic anhydrase (CA) uses H+ and HCO3- to form CO2 and H20, which diffuse into the cell. Within the cell, intracellular CA reverses the process, using CO2 and H2O to form H+ and HCO3-. The H+ is pumped back into the lumen via NA/H antiporters, while the HCO3- is transported across the basolateral membrane with HCO3-/Na symporters (in nephron) and HCO3-/Cl- exchangers (in collecting duct).
This process is present in the PT, thin ascending loop, and collecting duct.
Potassium reabsorption in PT
Reabsorption of K+ in the PT occurs by paracellularly by solvent drag between cells.
Reabsorption occurs here regardless of dietary K+ levels.
Potassium reabsorption in thick ascending loop of Henle
Na/K/Cl cotransporters, as well as continued paracellularly by solvent drag, reabsorb K+ into cell. It is crosses the basolateral membrane by diffusion.
Reabsorption occurs here regardless of dietary K+ levels.
Potassium reabsorption in distal tubules
Earlier in the nephron, K absorption occurs regardless of dietary K+ levels. In the distal tubule and collecting duct, K+ may be either reabsorbed or excreted, depending on needs.
If plasma K+ is high, aldosterone acts on basolateral Na/K pumps to increase activity. K+ is pumped into the cell and is secreted into the lumen along its concentration gradient.
Potassium reabsorption in collecting duct
Similar to the distal tubule, aldosterone can act on the basolateral Na/K pumps to secrete K+ when plasma levels are high.
If plasma K+ levels are low, an apical H+/K+ symporter will reabsorb K+ in exchange for H+. The K+ crosses the basolateral membrane via a K+/Cl exchanger.
Aldosterone and K+ levels
When plasma K+ is high, aldosterone is released. It acts to stimulate the activity of Na/K pumps in the distal tubule and collecting duct to increase K+ secretion.
Aldosterone is also released due to decreased renal blood flow through RAAS.
Hypertension and Na+ transporters
Targeting specific renal sodium transporters can control hypertension. Blocking reabsorption of Na+ increases Na+ and water secretion, reducing blood volume. This is a target for thiazide diuretics.
Calcium handling in PT
The majority of Ca+ in plasma is bound to proteins, and therefore not filtrated. That which is in the filtrate is mostly absorbed paracellularly by solvent drag. It tends to follow Na gradients.
Distal tubule and Ca2+
Only a small amount of Ca is reabsorbed in the distal tubule, yet this is the site of regulation. Ca reabsorption is controlled here by PTH (parathyroid hormone). PTH, in response to low Ca plasma levels, increases apical Ca channels and basolateral Na/Ca basolateral exchangers.
PTH
Parathyroid hormone is a hormone secreted by the parathyroid glands that essentially increase blood calcium levels. In the kidney, PTH increases CA levels by opening Ca channels in the distal tubule.
It also decreases the number of PT apical Na/P cotransporters, thereby increasing secretion of phosphate.
Phosphate handeling
Phosphate is critical for the bone metric as well as intracellular energy mechanisms. Most of plasma phosphate is filtered by the glomerulus, most of which is reabsorbed in the PT by apical Na/P cotransporters.
Renal P reabsorption is primarily controlled by PTH, which effects the number of Na/P cotransporters. Unlike Ca reabsorption, which is increased by PTH, phosphate reabsorption is decreased.
Kidney stones
Mineral aggregates of Ca2+ and oxalate that form in the kidney or uretors. Can result in renal failure, and cause pain and vomiting.
Hypoatremia
Low plasma Na+ levels. Fluid shifts into cells, establishing normal osmolarity but causing cellular swelling.
Exercise induced Hypoatremia
Can occur due to fluid and electrolyte loss during exercise. Symptoms include vomiting, nausea, bloating, headaches, disorientation.
How is sodium reabsorbed in the first and second halves of the PT?
In the first half, Na crosses the apical membrane via H+ exchangers.
In the second half, it crosses paracellularly with Cl-.
Aquaporins
AQP1, channels through which water is reabsorbed in thin descending limb.
How much of the filtrate is reabsorbed in the PT? And is is variable or regulated?
70%. The PT is not regulated and therefore the volume reabsorbed normally does not vary.
How much of the filtrate is reabsorbed in the Loop of Henle? And is is variable or regulated?
20%. The loop of Henle is not regulated and therefore the volume reabsorbed does not normally vary.
What part of the Nephron regulates the bodies salt and water balance? What percentage of the filtrate is it concerned with?
The collecting duct. 10%
What hormone regulates Sodium concentration?
Aldosterone
What hormone regulates Water concentration?
ADH
