Week 15 Flashcards
(33 cards)
What occurs in the ascending limb of the loop of Henle?
In the Thick Segment (near the distal convoluted tubule) salt is actively extruded from filtrate into cells by a Na+ K+ 2Cl- cotransporter (Na+ goes down gradient and K+ and 2Cl- in same direction). Then Na+ is actively transported across basolateral membrane into interstitial fluid by Na+/K+ pumps and Cl- follows it while K+ diffuses back into filtrate. The net effect is that NaCl is extruded into interstitial fluid, AND the loop of henle is not permeable to water so filtrate is increasingly dilute (hypotonic) as it ascends while interstitial fluid is more concentrated (hypertonic)
What occurs in the descending limb of Henle
The descending limb does not actively transport salt and is impermeable to salt. It is permeable to water, so as the interstitial fluid is hypertonic (due to ascending limb action), water is drawn out of the descending limb by osmosis and enters blood capillaries. Tubular fluid concentration is thus increased while its volume decreases and as it rounds the bend at the tip of the loop it has the same osmolality (super high) as the interstitial fluid. So a higher salt concentration arrives in the ascending limb due to the descending limb.
What occurs in the collecting duct?
At the collecting duct, the interstitial fluid is hypertonic and the fluid passing into the collecting duct is hypotonic due to the loop of Henle. The collecting duct is impermeable to NaCl and so water is drawn out of the collecting duct and transported by capillaries to vascular circulation. This osmotic gradient is necessary and normally constant, however adjustments to the permeability of the collecting ducts may be made by ADH (arginine vasopressin) regulating the number of aquaporins in the plasma membrane.
Review ADH! Where is it made, what triggers its release, what effect does it cause and how
antidiuretic hormone (arginine vasopressin) is made in the hypothalamus supraoptic and paraventricular nuclei, and stored in the posterior pituitary (neurohypophysis) where it is released in response to osmoreceptors (in the hypothalamus Thirst Center) that detect high plasma osmolality (dehydration, blood loss, excessive perspiration, hypotensive shock). ADH then stimulates (via cAMP) exocytosis of aquaporin vesicles in the collecting ducts to increase water permeability and reabsorption, decreasing urine volume. When ADH is not present b/c well hydrated, aquaporins are endocytosized and water reabsorption decreases, increasing urine volume
Describe the effects of drinking sea water
High salt content in sea water causes more water to remain inside the tubules and be urinated out along with the salt, this is *Osmotic Diuresis. So more water is urinate out than seawater taken in and you remain thirsty, result is death quicker than if you didn’t drink at all
What is renal clearance and what processes determine the rate
Ability of kidneys to remove molecules from the blood plasma by excretion in urine. Filtration promotes renal clearance an d reabsorption reduces renal clearance. Secretion is the opposite of reabsorption as molecules are transported across tubular epithelial cells into the lumen of the nephron tubule, this increases renal clearance. So the excretion rate = filtration rate + secretion rate - reabsorption rate
What measurement assesses kidney health? What substance is used to get this measurement?
Glomerular Filtration Rate (GFR) measures the volume of blood plasma filtered per minute by the kidneys, and must use a substance which is neither reabsorbed nor secreted so excretion rate = filtration rate. Xenobiotics are foreign molecules that meet this criteria and includes Inulin which can be used to determine GFR. Another molecule which is produced by the body is *CreatINine, a product of creatine, which is only slightly secreted so GFR is very closely determined.
How is glucose and amino acids reabsorbed? Can there be too much glucose to reabsorb? What would this cause?
Normally these are not present in urine at all because the proximal tubule has secondary active transport where glucose/amino acids and Na+ are cotransported out. There is a saturation point or Transport Maximum where glucose carriers are saturated and excess glucose would spill over into the urine, however it is super high in normal kidneys so normally there is full reabsorption of glucose. Glycosuria (glucose in urine) will occur if Tm is lower than it should be and Renal Plasma Threshold (concentration that results in excretion of the substance) is reached. This is Diabetes Mellitus, when inadequate insulin causes hyperglycemia. *Osmotic diuresis occurs as glucose in urine draws water out with it!
Describe the mechanism of aldosterone regulation of Na+. What drugs target this mechanism?
Aldosterone (secreted by the adrenal cortex in response to angiotensin II when Na+ is low) regulates reabsorption of Na+ in the late distal tubule and, more importantly, the Cortical Region of the Collecting Duct. 90% of Na+ reabsorption occurs prior to this in the early nephron and is not subject to hormone regulation, but the final amount of regulation is very significant in total volume. Aldosterone stimulates Na+/K+ pumps in the basolateral membrane which increases the electrochemical gradient through Na+-Cl- cotransporters in the apical membrane. Diffusion of Na+ into the cell creates a negative charge in the lumen that drives Cl- in. Thiazide Diuretics target these apical Na+-Cl- cotransporters
Describe how aldosterone regulates potassium
90% of potassium is reabsorbed from filtrate in the proximal tubule, any K+ that appears in urine must have been secreted in the Late distal tubule and Cortical collecting duct. Eating a high K+ meal stimulates the adrenal cortex to secrete aldosterone which the increases K+ secretion into filtrate, so plasma K+ is constant. (K+ channels are also inserted/removed in late distal tubule and cortical collecting duct membranes independently of aldosterone). K+ is secreted by the Na+/K+ pump and by diffusion through K+ channels promoted by the reabsorption of Na+ creating a potential difference that drives K+ into filtrate. Therefore increased Na+ also promotes K+ secretion.
How does Na+ regulate K+ secretion? Describe three ways. These mechanisms help explain how diuretic drugs produced what condition?
Na+ reabsorption creates a potential difference that drives K+ into the filtrate (the more negative space) so increased Na+ reabsorption will cause increased K+ secretion. Increased Na+ also stimulates the juxtaglomerular apparatus to secrete renin and activate aldosterone, which promotes K+ secretion. Lastly, the distal tubule cells contain *primary cilium that respond to increased flow rates (and increased Na+ delivery) to activate K+ channels and lead to increased K+ secretion.
This explains why diuretic drugs create hypokalemia (low blood potassium) because they increase urination by delivering more Na+ to the distal tubule, which causes more K+ secretion
What conditions control aldosterone secretion? Review the whole system which leads to aldosterone release
High K+ depolarizes aldosterone secreting cells to directly stimulate aldosterone secretion. Low Na+ indirectly promotes aldosterone secretion by the renin-angiotensin-aldosterone system: Justaglomerular apparatus (where afferent arteriole contacts thick ascending limb of loop) contains granular cells which secrete renin. Renin converts angiotensinogen into angiotensin I. Angiotensin Converting Enzyme (ACE) converts angiotensin I to angiotensin II in lungs. Angiotensin II causes aldosterone secretion from adrenal cortex, it also causes vasoconstriction (raise blood pressure) and acts on kidneys to promote sodium transporters and decrease GFR and sodium excretion
What causes increased renin secretion?
A fall in blood volume and fall in renal blood flow (as a result of low NaCl intake which inhibits ADH so more water is excreted in urine). The direct effect of blood pressure on the granular cells, which are baroreceptors!, increases renin.
Sympathetic nerve activation of B1-adrenergic receptors on granular cells also increases renin - this occurs during the baroreceptor reflex.
Describe how K+ concentration affects H+ concentration in the nephron. What is the effect of acidosis, alkalosis, hyperkalemia, high aldosterone, and low aldosterone
In the late distal tubule and cortical collecting ducts, positively charged ions (K+ and H+) are secreted in response to negativity created by Na+ reabsorption. A H+/K+ pump also moves H+ into filtrate and K+ into the cell. This pump is activated by acidosis, causing rise in blood K+. Alkalosis causes increased secretion of K+ into filtrate. Hyperkalemia causes increased K+ secretion and decreased H+ secretion (can cause acidosis!). High aldosterone (Conn Syndrome) causes K+ and H+ secretion, producing hypokalemia and alkalosis. Low aldosterone (Addison’s disease) can produce hyperkalemia and acidosis.
describe the process of H+ and HCO3- reabsorption in the PROXIMAL tubule
The proximal tubule uses Na+/H+ anti port carriers that move Na+ in the cell (with gradient) and H+ out the cell into filtrate (against gradient), this is secondary active transport. The secreted H+ is used to reabsorb bicarbonate because the apical membranes of the tubule cells are impermeable to bicarbonate! So reabsorption occurs by HCO3- combining with H+ to make carbonic acid which converts to CO2 and H2O via Carbonic anhydrase. CO2 diffuses into the cells where carbonic anhydrase converts it back into carbonic acid, which dissociates to HCO3- and H+ and can be released into the blood stream on basolateral sides. This process amounts for the reabsorption of 80-90% of bicarbonate and leaves very little H+ in the filtrate.
What occurs in the DISTAL tubule to cause acidification of the urine?
the distal tubule secretes H+ into the filtrate using primary active transport H+ (ATPase) pumps. H+ has to be buffered in urine, and bicarbonate can’t serve this function as it is reabsorbed. Phosphates (HPO42-) and ammonia (NH4) are the main buffers. Phosphate enters urine by filtration and ammonia enters urine by deamination of glutamine in the tubule cells. Acidosis increases ammonia production and it concentrates in the medullar, creating a gradient to favor diffusion of ammonia into the collecting duct and increased H+ secretion (raising pH to counter acidosis)
Describe what happens in urinary reabsorption if a person has alkalosis and acidosis
response to Respiratory Alkalosis: less H+ is present so less HCO3- is reabsorbed. Increased excretion of HCO3- compensates for alkalosis Decreased bicarbonate (due to excess ketone bodies or lactic acid) can cause primary metabolic acidosis which triggers respiratory response
response to Respiratory Acidosis: extra H+ is buffered by increasing bicarbonate ions produced by Bicarbonate Generation from metabolism of Glutamine (formed from glutamate in the Proximal Tubules) that produces two bicarbonate ions. Ammonia is also produced and serves as a buffer, although most is cleared by the liver.
Increased plasma bicarbonate (due to loss of acidic gastric juice/vomiting) can cause primary metabolic alkalosis which triggers respiratory response
What are diuretics and what conditions would they be used for
Diuretics increase the volume of urine excreted and lower the blood volume. They also lower blood pressure and interstitial fluid volume. This makes them helpful in treating hypertension, congestive heart failure, or edema.
name the types of diuretics and give examples of each
Loop Diuretics (furosemide/Lasix): most powerful, reduce salt/water reabsorption by inhibiting Na+/K+/2Cl- cotransporters in the thick ascending limb Thiazide diuretics (Hydrochlorothiazide): inhibit salt/water reabsorption by inhibition of sodium-chloride cotransporters in the distal convoluted tubule Carbonic Anhydrase Inhibitors (acetazolamide/Diamox): weaker, act in proximal tubule to prevent bicarbonate/water reabsorption. Also used to treat acute mountain sickness. Osmotic Diuretics (Mannitol, also salt water and ketosis from diabetes mellitus): extra solutes in filtrate decrease water reabsorption by osmosis.
Many diuretics cause what side effect? What other diuretics may be used to prevent this?
Hypokalemia because K+ secretion is stimulated by increased Na+ delivery used to increase urination. Hypokalemia may produce neuromuscular disorders and ECG abnormalities, people on diuretics often take low Na+ diets and supplement K+. Potassium-sparing diuretics include:
Spironolactones (Aldactone) aldosterone antagonists to block aldosterone stimulation of Na+ reabsorption and K+ secretion
Triamterene (Dyremium) that directly blocks Na+ reabsorption and K+ secretion
Aldactazide or Dyazide (combinations of the previous two with hydrochlorothiazide)
Name renal function tests and the diseases they may diagnose
Test renal function by measuring total blood flow to kidneys and GFR (inulin clearance). Plasma Creatine Concentration also provides good test. May diagnose *Glomerulonephritis (autoimmune disease triggered by streptococcus infections destroys glomeruli, remaining glomeruli leak and causes edema) and renal insufficiency. Acute renal failure (kidneys fail over short time - hours to days) causes rise in blood creatinine and decreased renal clearance of creatinine.
Urinary Albumin Excretion Rate is performed to detect excretion of albumin and diagnose Microalbuminuria (manifestation of renal damage from diabetes or hypertension). Proteinuria is when protein is in urine, large excretion is Nephrotic Syndrome. Diabetic kidney disease results in proteinuria and leads to end-stage renal disease.
What is renal insufficiency and how is it treated
Renal insufficiency is when nephrons are destroyed, may be due to glomerulonephritis, pyelonephritis (infection), loss of kidney, or damage caused by diabetes or kidney stones. Causes hypertension and uremia (high plasma urea) due to inability to excrete urea and elevated plasma H+ (acidosis) and elevated K+. Uremic coma may occur!
Dialysis treatment: “artificial kidney machine” or hemodialysis cleans blood by passing it through a permeable membrane so wastes filter out into dialysis fluid. The dialysate has high Na+, K+, and glucose so they don’t filter out and very high bicarbonate so it diffuses into blood. Continuous ambulatory Peritoneal Dialysis (CAPD) is when the patients own peritoneal cavity is used as the membrane and dialysis fluid is introduced into the cavity. Its more convenient, but less efficient and may cause infection
What happens during stage 3 of birth
The placenta or afterbirth is delivered by uterine contractions
What problem can occur during birth and require a c section
If the fetus does not turn, a breech birth occurs where the rump comes first. The cervix cannot expand to accommodate this and asphyxiation is likely, so a Cesarean section (incision through abdominal and uterine walls) may be needed. But, C-sections are being done too much, almost 30%
