Week 15

Question 1

What occurs in the ascending limb of the loop of Henle?

Answer 1

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)

Question 2

What occurs in the descending limb of Henle

Answer 2

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.

Question 3

What occurs in the collecting duct?

Answer 3

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.

Question 4

Review ADH! Where is it made, what triggers its release, what effect does it cause and how

Answer 4

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

Question 5

Describe the effects of drinking sea water

Answer 5

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

Question 6

What is renal clearance and what processes determine the rate

Answer 6

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

Question 7

What measurement assesses kidney health? What substance is used to get this measurement?

Answer 7

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.

Question 8

How is glucose and amino acids reabsorbed? Can there be too much glucose to reabsorb? What would this cause?

Answer 8

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!

Question 9

Describe the mechanism of aldosterone regulation of Na+. What drugs target this mechanism?

Answer 9

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

Question 10

Describe how aldosterone regulates potassium

Answer 10

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.

Question 11

How does Na+ regulate K+ secretion? Describe three ways. These mechanisms help explain how diuretic drugs produced what condition?

Answer 11

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

Question 12

What conditions control aldosterone secretion? Review the whole system which leads to aldosterone release

Answer 12

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

Question 13

What causes increased renin secretion?

Answer 13

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.

Question 14

Describe how K+ concentration affects H+ concentration in the nephron. What is the effect of acidosis, alkalosis, hyperkalemia, high aldosterone, and low aldosterone

Answer 14

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.

Question 15

describe the process of H+ and HCO3- reabsorption in the PROXIMAL tubule

Answer 15

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.

Question 16

What occurs in the DISTAL tubule to cause acidification of the urine?

Answer 16

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)

Question 17

Describe what happens in urinary reabsorption if a person has alkalosis and acidosis

Answer 17

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

Question 18

What are diuretics and what conditions would they be used for

Answer 18

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.

Question 19

name the types of diuretics and give examples of each

Answer 19

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.

Question 20

Many diuretics cause what side effect? What other diuretics may be used to prevent this?

Answer 20

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)

Question 21

Name renal function tests and the diseases they may diagnose

Answer 21

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.

Question 22

What is renal insufficiency and how is it treated

Answer 22

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

Question 23

What happens during stage 3 of birth

Answer 23

The placenta or afterbirth is delivered by uterine contractions

Question 24

What problem can occur during birth and require a c section

Answer 24

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%

Question 25

What are 4 characteristics seen on newborns?

Answer 25

The skin is covered with a white, greasy, cheese-like substance called “vernix caseosa” which protects the skin.
Intestines are filled with green/paste-like material called “meconium” which is high in bilirubin.
Babies may have breasts swell and secrete small drops of milk (both girls and boys).
Girls may have a small period (menses).

Question 26

Describe the structure of a mammary gland

Answer 26

Each gland is composed of lobes divided by adipose (amount of adipose = size/shape of breast). Lobes are divided into lobules which contain alveoli that secrete milk into a series of secondary tubules. These merge to form a lactiferous duct that drains at the nipple. The lumen of each lactiferous duct expands just beneath the nipple surface to form a lactiferous sinus (ampulla) where milk accumulates. Specialized myoepithelial cells contract to propel milk through this system

Question 27

What hormone triggers lactation and how is it regulated? What drug inhibits it?

Answer 27

Prolactin stimulates milk production. Prolactin secretion is controlled by Prolactin-Inhibiting Hormone (PIH), aka Dopamine, secreted from hypothalamus to the anterior pituitary where prolactin is. PIH is inhibited by estrogen, so during pregnancy when estrogen is high, prolactin secretion increases. However, high progesterone and estrogen during pregnancy inhibit the ability of prolactin to stimulate mammary glands until after parturition. After birth, declining progesterone and estrogen allow prolactin to stimulate milk production (colostrum is rich first milk). The act of nursing maintains high prolactin secretion.
Bromocriptine binds dopamine receptors and increases prolactin inhibition

Question 28

Describe the reflexes involved in lactation

Answer 28

A neuroendocrine reflex occurs when sucking stimulus affects the hypothalamus to inhibit secretion of PIH, thus high prolactin promotes secretion of milk.
For the baby to get milk, oxytocin is also stimulated by this reflex and its release results in milk-ejection reflex or milk letdown. Oxytocin stimulates contraction of myoepithelial cells.
Milk letdown can become a conditioned reflex in response to visual/auditory cues like baby crying. Sympathetic activity present if mother is anxious can inhibit the reflex.

Question 29

What is contained in breast milk that makes it great

Answer 29

A lot of nutrients like vitamins, carbohydrates, hormones, growth factors, and immunoglobulin A. The colostrum is the first milk and is yellow, thick and full of IgA antibodies and other constituents to promote active immunity. It is recommended that mothers exclusively breast feed for the first 6 months.

Question 30

What is Probenecid used for and how does it work?

Answer 30

Probenecid is a drug used to treat gout by improving the ability of the kidneys to eliminate uric acid from the blood. It inhibits the uric acid transporters in the proximal tubule, reducing the renal reabsorption of uric acid and promoting its excretion. During World War II, when penicillin was in short supply, probenecid was used to inhibit the organic anion transporters (OATs) in the proximal tubule, reducing the renal secretion of penicillin. This reduces the rate at which penicillin is cleared, increasing its effectiveness and decreasing its nephrotoxicity. Probenecid may still be used in severe infections to increase the effectiveness of penicillin and other antibiotics—including ampicillin and cephalosporin—that are secreted into the nephron by OATs.

Question 31

How is eGFR determined? What is a BUN?

Answer 31

Creatinine is produced in muscles from creatine and released into the blood plasma, where its concentration is used to help assess kidney function. Creatinine is filtered in the kidneys and not reabsorbed, but it is slightly secreted by the tubules. This gives it a renal plasma clearance a little greater than that of inulin (a little greater than true GFR). However, its plasma concentration, together with a person’s age, sex, and weight, is frequently used in equations to calculate an estimated GFR (eGFR). Also, the ratio of the plasma concentrations of urea (called a BUN—blood urea nitrogen—test) to creatinine provides additional information about kidney health.

Question 32

What are the symptoms and causes of hyperkalemia and hypokalemia? What diseases can cause these?

Answer 32

Hyperkalemia (high K+) symptoms include nausea, weakness, and changes in the ECG. Aldosterone is required for elimination of K+ by stimulating the secretion of K+ into the cortical collecting ducts, and so adrenal insufficiency (produced by Addison’s disease) can cause hyperkalemia as well as hyponatremia (low plasma Na+).
Hypokalemia (low K+) can produce heart arrhythmias and muscle weakness. It is most commonly caused by the use of certain diuretics or vomiting and metabolic alkalosis, but can also be caused by the excessive aldosterone secretion of primary hyperaldosteronism (Conn syndrome) or Cushing syndrome.

Question 33

What signal is secreted by the heart to cause diuresis? What can measurement of this molecule help diagnose?

Answer 33

In addition to atrial natriuretic peptide, scientists have discovered a natriuretic hormone released by the heart’s ventricles called B-type natriuretic peptide (BNP). BNP is secreted in response to increased volume and pressure within the ventricles, and it acts like ANP to promote diuresis. Because the secretion of BNP increases in congestive heart failure (CHF), measurements of the blood level of BNP are used clinically to help diagnose CHF. This is especially useful in distinguishing cardiac versus pulmonary causes of a patient’s dyspnea (difficulty breathing).