Urine, ECF, Osmolarity

Question 1

Thin descending loop of Henle

Answer 1

Permeable to water, impermeable to the reabsorption of solutes. Water is reabsorbed while solute gain in concentration.

It is the concentrating segment.

Question 2

Thick ascending loop of Henle

Answer 2

Impermeable to water, but Na/K/Cl cotransporters facilitate the reabsorption of solutes.

Tubule contents are diluted.

Question 3

Distal tubule

Answer 3

Normal tubule concentration here is 100mosm/L. In response to elevated ECF osmolarity or decreased ECF volume, Antidiuretic hormone (ADH) is secreted by the posterior pituitary gland into the blood. ADH allows for the solute-free reabsorption of water, and thus the concentration of urine.

Question 4

Medullary interstitium

Answer 4

As the nephron decends into the medulla, the osmolarity of the interstitial increases from 300 to 1200 mosm/L. This compels water to be reabsorbed while deciding an secreted while ascending.

Question 5

Countercurrent multiplier

Answer 5

The countercurrent multiplier allows for the establishment of an osmolar gradient from the cortex to the medulla. It is the repeated cycle in which solutes are transported out of the thick ascending limb (which raises osmolarity of the interstitial fluid), and water is absorbed from the thin descending limb (which further concentrates the tubular fluid as it enters the think ascending limb.

Question 6

ADH (aka vasopressin)

Answer 6

Synthesized in the hypothalamus and stored/secreted by pituitary gland upon a 1% increase in plasma osmolarity or a significant decrease in plasma volume.

Its two primary functions are to retain water in the body and to constrict blood vessels. ADH regulates the body’s retention of water by making the CD epithelium impermeable to water.

The maximum concentration of urine in 1200mosm/L, as accordant to the osmotic gradient in the loop of Henle interstitium.

Question 7

Dilution of urine

Answer 7

An excess of ECF increases GFR and decreases osmolarity. Increased renal blood flow (and vasa recta flow) results, which washes out the solutes of the interstitium. A decreased osmolar gradient in the interstitium coupled with the increased GFR reduces water reabsorption. ADH is also decreased, so the CD does reabsorb water. The result is hypotonic urine. After urination, the interstitial concentration gradient is established.

Question 8

Route of urine formation

Answer 8

Collecting ducts -> Ducts of Bellini -> Ureter -> Bladder -> urethra.

Question 9

3 steps to urine formation

Answer 9

Filtration of blood at glomerulus
Tubular reabsorption
Tubular secretion

Question 10

Describe the route of flow to and from the nephron:

Answer 10

Renal artery -> Interlobar art -> Arcuate art -> Interlobular art -> afferent arteriole -> glomerular capillaries -> efferent arterioles -> peritubular capillaries -> interlobular vein -> arcuate vein -> interlober vein -> renal vein.

Question 11

Steps involved in myogenic response to increased blood pressure.

Answer 11

increased BP -> increase pressure in afferent arteriole -> stretch of arteriole wall -> muscle contracts, increasing arteriole resistance and decreasing RBF accordingly.

Question 12

Macula densa

Answer 12

Region of specialized cells in the Thick ascending limb of loop of Henle, which makes close contact to the afferent arterioles. It senses GFR changes by monitoring NaCl content.

In the event of high GFR, the macula dense releases adenosine, which diffuses into the arterioles and causes constriction, thereby reducing RBF and GFR.

Question 13

What is normal GFR in adults?

Answer 13

90-140 mL/min in males
80-125 mL/min in females

Minus 10 for young adults

RBF decreases with age

Question 14

Adenosine?

Answer 14

Released at macula dense in response to high GFR. It acts to contract afferent muscles to reduce RBF and GFR.

Question 15

What nervous system acts on kidneys to regulate RBF and GFR?

Answer 15

Sympathetic. Causes vasoconstriction.

Question 16

What hormones act to regulate RBF and GFR?

Answer 16

Vasoconstriction -> reduce RBF/GRF
         Adrenaline, angiotensin 2, adenosine. 
Vasodilation -> increase RBF/GFR
         Bradykinin
         Prostaglandins (PGE1, PGE2)

Question 17

What would be the kidneys response during high stimulus, exercise, etc?

Answer 17

Bodies blood pressure is high, therefore RBF is too high. Adrenaline and angiotensin 2 act to constrict renal arterioles, thereby reducing RBF and GFR.

Question 18

Plasma colloid pressure

Answer 18

Suction pressure from the bowman’s capsule into the the glomerular capillaries that is caused by bulky proteins in the plasma.

This opposes the Glomerular capillary blood pressure.

Question 19

Glomerular filtration barrier

Answer 19

Consists of three layers, all of which contain negatively charged glycoproteins.

endothelium (of capillaries)
basement membrane
epithelium

Question 20

What passes through glomerular filtration barrier?

Answer 20

All components of plasma, except cells and proteins. The negative charge of the barrier repels negatively charged proteins.

Question 21

Nephrotic syndrome

Answer 21

Nephrotic syndrome is a syndrome comprising signs of nephrosis, chiefly proteinuria, hypoalbuminemia, and edema.

Essentially, a reduction in the glycoproteins in the glomerulus (can be due to autoimmunity) causes excess filtration of proteins (notably albumin). The loss of protein through the kidneys (proteinuria) leads to low protein levels in the blood (hypoproteinemia including hypoalbuminemia), which causes water to be drawn into soft tissues (edema).

Question 22

Minimal change disease

Answer 22

Minimal change disease is a disease affecting the kidneys which causes a nephrotic syndrome.

Question 23

Measuring GFR

Answer 23

Creatinine clearance test.

Creatine is a small protein that can be filtered but is not reabsorbed (for the most part).

Question 24

How much urine formed per day?

Answer 24

0.7-1.5 L/day

Question 25

How much filtrate processed per day?

Answer 25

160 L/day

Question 26

How much filtrate enters the collecting duct, and how much is reaborbed/excreted during hyper hydrated, normal, and dehydrated condition?

Answer 26

12mL of filtrate enters CD each minute. When very hydrated, all 12 mL can be excreted as urine. When dehydrated, as much as 11.5 mL will be reabsorbed. In normal conditions, 11 mL/min is reabsorbed, producing 1mL of urine per minute.

Question 27

Juxtamedullary nephrons

Answer 27

Nephrons with longer loops of Henle, which have a greater ability to concentrate the interstitium.

Question 28

Urea in the CD

Answer 28

The CD is permeable to urea. Some will diffuse out of the CD into the interstitium, where it will enter the thick ascending limb. Thus, urea can be recycled in this way.

Question 29

How and where is water balance monitored?

Answer 29

The body does not measure water content, but rather osmolarity of the plasma. This occurs in osmoreceptors in the hypothalamus. They will respond to a 1% change in osmolarity.

They are activated by increases in osmolarity above 280. They activate thirst and the release of ADH.

Question 30

What is the range of urine osmolarity?

Answer 30

Urine osmolarity depends on hydration.

In a well hydrated person it can be as dilute as 30 mosmol/L and 1200 mosmol/L in a dehydrated person.

Normal range is 600-800 mosmol/L.

Question 31

Hyponatremia

Answer 31

Hyponatremia is a low sodium level in the blood. Symptoms can vary from a decreased ability to think, headaches, nausea, and poor balance, confusion, seizures, and coma. Normal serum sodium levels are 135–145 mmol/L. Hyponatremia is generally defined as a serum sodium level of less than 135 mmol/L and is considered severe when the level is below 120 mmol/L.

This is generally the result of salt loss. The result is an increased serum and intracellular fluid osmolarity, resulting in H20 moving into cells, disrupting cellular function.

Question 32

What percentage of bodily fluid reduction causes death?

Answer 32

25%

Question 33

Causes of overhydration

Answer 33

• Kidney failure decreases GFR, so excess water is not excreted.
• SIDH; inappropriate secretion of ADH, leading to fluid retention.
• Sweating salt while replenishing water.

Question 34

SIDH

Answer 34

Syndrome of inappropriate ADH secretion. Leads to over hydration (increase of plasma osmolarity). Can be caused by pulmonary disease and lung tumors, which causes secretion of ADH like peptides.

Treatment includes fluid restriction, ADH inhibitor, or hypertonic solution.

Question 35

Causes of under-hydration

Answer 35

• Diabetes insidious; inadequate release of ADH from pituitary.
• Nephrogenic diabetes insidious; collecting ducts do not respond normally to ADH.

Question 36

Diabetes insipidus

Answer 36

Inadequate release of ADH from posterior pituitary, causing dehydration. May be caused by head trauma or brain infection.

Question 37

Nephrogenic diabetes insidious

Answer 37

Collecting ducts do not respond normally to ADH. Results in dehydration. May be induced by certain drugs.

Hard to treat. Low salt diets.

Question 38

How to clinically distinguish between DI and NDI?

Answer 38

Both result in dehydration. However, DI is the inadequate production of ADH and NDI is the inadequate response to ADH.

Patients should be very well hydrated and then deprived from water for 8 hours, during which their urine osmolarity is measured. ADH is then administered and urine osmolarity is again measured.

The dministration of ADH should help patients with DI but not NDI.

Question 39

What percent of plasma osmolarity does Na account for?

Answer 39

50%

Question 40

Amino Acid metabolism (general)

Answer 40

Protein is has a high turnover rate. Alanine in muscle travels through plasma to liver, where it is deaminated by an amino transaminase (using keto-glutamate as the amino mop), which produces pyruvate. Keto-glutamate can help in the catabolism of many amino acids, including aspartate to oaxalacetate.

The newly synthesized glutamate carries an amino group that upon deamination, undergoes the urea cycle, which converts toxic NH3 to urea. Deamination is carried out by glutamate dehydrogenase.

Question 41

Urea cycle; where does it take place and what are the starting materials?

Answer 41

Mitochondria within liver cells. starting products are NH3 and C02.

Question 42

Characteristics of urine?

Answer 42

93-97% water
pH 4.5-8
1200 mL/day average

Question 43

Urine components

Answer 43

Water
Urea
Creatinine
Ammonia (little)
Uric acid (little)
Ketone bodies
Urobilinogen
Inorganic ions

Question 44

Uric acid

Answer 44

End product of purine metabolism

High levels can lead to deposition and inflammation in joints - gout.

Question 45

Urea in the nephron/CD

Answer 45

Urea is concentrated as it reaches the collecting duct. Some urea even enters from the interstitium at the ascending loop.

Small amounts of concentrated urea can be reabsorbed into the interstitium from the collecting duct.

Question 46

Proteinurea

Answer 46

Increased amount of protein in urea.

• Benign proteinurea - normal protein secretion
• tubular proteinurea - normal small proteins in filtrate, but failure to reabsorb in PT.
• Overload proteinurea - due to pre renal protein excess.
• Glomerular proteinurea - larger proteins get through glomerular filtration (mainly albumin).

Question 47

What can a dipstick test?

Answer 47

pH, glucose, protein, creatine, ketones, bilirubin.