Water Balance, Acid/Base Balance, Calcium, Mg, and Phosphate Homeostasis

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Patho/Physio 2 Schreier NSU Pharmacy Packets 6-8

PCT

Where is most water reabsorbed?

thin descending limb

Which part of the Loop of Henle is permeable to water?

the sharp turn

Which part of the Loop of Henle is permeable to urea?

thick ascending limb

Which part of the Loop of Henle has the Na/K/Cl cotransporter?

helps create concentrated urine

What is the role of the counter current mechanism?

~water flows out into the interstitial fluid creating a more concentrated filtrate in the loop and helping the body retain water
~Because the descending limb is highly permeable to water, water moves by osmosis here. As described above, it moves out of the tubule and into the medullary interstitial fluid for reabsorption

What is the role of the descending limb in the loop of henle?

pumps solutes out of the filtrate and into the medullary interstitial fluid for reabsorption;
helps maintain the concentration gradient

What is the role in the ascending limb of the loop of henle?

the vasa recta are a group of peritubular capillaries that run along the loop of henle in the kidney. The blood in the vasa recta flows the opposite direct of the filtrate in the loop of henle creating the counter current exchange mechanism.

What is the vasa recta?

helps maintain hypertonicity in the renal medulla and helps return electrolytes and fluids to the blood supply
~salt reabsorbed from the Loop of Henle is trapped and recycled within the medulla by the countercurrent flow of blood in the vasa recta

What is the role of the vasa recta?

-loop diuretic
-affects the thick ascending limb
-blocks Na/K/Cl symport
-results in : decreased NaCl reabsorption, decreased K+ reabsorption, decreased potential in lumen, decreased paracellular mechanism for cation reabsorption

What are the effects of furosemide?

1. ADH
2. aldosterone (RAAS)

What are the two hormonal ways that the body increases blood volume?

ANP

What is the hormonal way that the body decreases blood volume?

cardiac muscle cells when atrial blood pressure increases

Where is ANP released from?

ADH and aldosterone

What two hormones does ANP inhibit the release of?

causes vasodilation

Does ANP causes vasoconstriction or vasodilation?

decrease

Does ANP increase or decrease blood pressure?

decrease

Does ANP increase or decrease blood volume?

increase

Does ANP increase or decrease urine output?

1. angiotensinogen is produced in the liver
2. cells of the juxtaglomerular apparatus in the kidney sense a drop in blood pressure and secrete renin
3. renin converts angiotensinogen to angiotensin I
4. ACE then converts angiotensin I to angiotensin II
5. angiotensin II causes vasoconstriction which helps return blood pressure back to normal
6. angiotensin II tells the adrenal cortex to secrete aldosterone
7. aldosterone causes the kidney to increase sodium and water reabsorption and decrease urine volume which also helps return blood pressure to normal

Describe the mechanism of action of the RAAS.

stretching of the osmoreceptors in the atria and ventricles occurs as a result of an increase in blood pressure; then signals are sent to the brain which cause ANP to be released from the heart muscle cells to normalize the BP

What causes the release of ANP?

a proteolytic enzyme that converts angiotensinogen to angiotensin I and is released by the juxtaglomerular cells of the kidney in response to a decrease in blood pressure;

What is the role of renin?

causes vasoconstriction and the release of aldosterone and ADH to increase blood pressure

What is the role of angiotensin II?

B. angiotensin II
E. high serum K+

Which are the two main factors that stimulate the production of aldosterone?
A. high serum Na+
B. angiotensin II
C. ANP
D. ADH
E. high serum K+

C. adrenal cortex

Where is aldosterone produced?
A. renal cortex
B. renal medulla
C. adrenal cortex
D. adrenal medulla
E. myocardium

~produced by the adrenal cortex
~increases reabsorption of Na+ in the distal tubule and collecting ducts of the kidney
~as a result water and chloride follow the sodium thus water retention
~promotes excretion of K+ and H+

What is the role of aldosterone?

in the distal tubule and collecting ducts of the kidney

Where does aldosterone act?

1. ANP
2. dopamine

Which two hormones decrease aldosterone release?

1. angiotensin II
2. increase in blood potassium levels
3. ACTH
4. decrease in blood sodium levels

What stimulates the release of aldosterone?

Tekturna (aliskiren)

What drug inhibits the action of renin?

decrease

What is the effect of aldosterone on sodium excretion by the kidney?

increase

What is the effect of aldosterone on potassium excretion by the kidney?

aldosterone secreting adrenal adenoma causing primary hyperaldosteronism

What is conn's syndrome?

aldosterone antagonist used to treat hyperaldosteronism

What is spironolactone?

ACE inhibitor

What is Lisinopril?

angiotensin II antagonist
~treats hypertension

What is losartan?

the hypothalamus

What part of the brain regulates water balance?

~increases blood volume and blood pressure
~causes insertion of aquaporins into the apical membrane for water reabsorption
~causes smooth muscle contraction leading to vasoconstriction

What is the role of ADH?

posterior pituitary

Where is ADH secreted?

1. increase in extracellular fluid osmolarity
2. angiotensin II
3. decrease in BP
4. decrease in extracellular fluid volume

What causes secretion of ADH?

1. ANP
2. ethanol

What inhibits secretion of ADH?

hypothalamus

Where is ADH produced?

the collecting duct of the kidney

Where does ADH act?

B. increase urine osmolarity

What does ADH do?
A. increase urine volume
B. increase urine osmolarity
C. increase urea excretion
D. increase sodium excretion

competitive ADH receptor antagonist

What is Tolvaptan?

1. secretes H+
2. reabsorbs and produces HCO3-
3. produces NH3, and excretes NH4+

What are 3 ways the kidney adjusts to maintain pH?

act to stabilize the pH of a liquid

What is the role of a buffer?

the bicarbonate buffer system

What is the primary buffer system for extracellular fluid?

the protein buffer system

What is the primary buffer system for intracellular fluid?

phosphate buffer system

What is the primary buffer of the urine?

bicarbonate

What is the major ion that influences the pH of the blood?

carbonic anhydrase converts CO2 + H20 to carbonic acid which can move across the membrane then converts to bicarbonate and H+

How is CO2 transported from the tissue to the lungs?

CO2 levels

What is the primary cause of respiratory acid/base imbalances?

False
It causes acidosis

True or False
Hypoventilation causes alkalosis.

true

True or False
Hyperventilation causes alkalosis.

PCT

Where is the majority of HCO3- reabsorbed?

its reabsorbed at CO2 and H20 from the filtrate and then converted back to HCO3-

How is bicarbonate reabsorbed?

carbonic anhydrase

What enzyme plays a major role in the reabsorption of bicarbonate?

the PCT and DCT

Where in the kidney does carbonic anhydrase act?

1. Glutamine is deaminated to produce NH3. NH3 takes H+ to form NH4+ and is excreted via the kidney
2. H+ combines with H2PO4-- to make H2PO4- and is excreted by the kidneys

How is excess H+ excreted?

a carbonic anhydrase inhibitor
~used to treat glaucoma and metabolic alkalosis

What is acetazolamide?

when the blood pH is below 7.35

What is acidemia?

when the blood pH is above 7.45

What is alkalemia?

less than 22 mEq/L

At what plasma level of bicarbonate classifies as metabolic acidosis?

greater than 28 mEq/L

At what plasma level of bicarbonate classifies as metabolic alkalosis?

1. rapid breathing
2. confusion or lethargy
3. shock

What are the symptoms of metabolic acidosis?

the difference in the measured cations and the measured anions in serum, plasma, or urine
~helpful when trying to determine the cause of metabolic acidosis

What is the anion gap?

1. lactic acidosis
2. ketoacidosis
3. renal failure
4. toxins

When the anion gap is increased what could be a possible cause of metabolic acidosis?

1. diarrhea
2. renal acidosis
3. ammonium chloride
4. acetazolamide

When the anion gap is normal what could be a possible cause of metabolic acidosis?

increase in pulmonary ventilation

What is the initial response to metabolic acidosis?

increased production of NH3 from glutamate

What is the primary adaptive response of the kidney to metabolic acidosis?

decrease in pulmonary ventilation

What is the initial response to metabolic alkalosis?

excrete excess HCO3-

What is the adaptive response of the kidney to metabolic alkalosis?

1. shallow breathing
2. hand tremor
3. light headedness
4. muscle twitching
5. nausea, vomiting
6. numbness or tingling in hands/feet
7. prolonged muscle spasms

What are the symptoms of metabolic alkalosis?

~hypercalcemia, renal insufficiency, and metabolic alkalosis that occurs in patients who ingest large amounts of milk or calcium carbonate antacids

What is milk alkali syndrome?

False

True or False
Metabolic acid/base imbalances are related to CO2 levels.

1. in the bone
2. as hydroxyapatite

Where is most of the body's calcium stored and what molecule is it stored as?

causes an increase in free Ca++ plasma concentration

What does acidosis do to calcium levels?

causes a decrease in free Ca++ plasma concentration

What does alkalosis do to calcium levels?

leads to respiratory alkalosis and decreases plasma levels of free calcium

What does hyperventilation do to calcium levels?

leads to respiratory acidosis and increases plasma levels of free calcium

What does hypoventilation do to calcium levels?

1. numbness
2. arrhythmias
3. osteoporosis
4. epilepsy
5. tetanic muscle contractions
6. paresthesias
7. neuromuscular irritability

What are the symptoms of hypocalcemia?

1. decreased neuromuscular excitability
2. decreased neurotransmission
3. muscle weakness
4. decreased GI motility
5. arrhythmias
6. hypertension
7. hypercalciuria
8. increased bone mass

What are the symptoms of hypercalcemia?

voltage sensitve sodium channels

What channels are sensitive to extracellular calcium concentration?

PCT

Where is most calcium reabsorbed?

~found in the PCT, DCT, collecting duct, and Loop of Henle
~sense extracellular fluid levels of calcium and make adjustments to keep levels normal in the blood

What is the kidney calcium receptor?

parathyroid hormone

What hormone regulates the reabsorption of calcium in the thick ascending limb in the Loop of Henle?

It enhances active reabsorption of calcium and magnesium from distal tubules and the thick ascending limb. It also decreases the reabsorption of phosphate, with a net loss in plasma phosphate concentration. When the calcium:phosphate ratio increases, more calcium is free in the circulation.

What is the role of parathyroid hormone in the kidney?

Calcitriol increases blood calcium levels by increasing renal tubular reabsorption of calcium thus reducing the loss of calcium in the urine. It also increases absorption of calcium in the GI tract.

What is the role of calcitriol in the kidney?

PTH reduces the reabsorption of phosphate from the proximal tubule of the kidney, which means more phosphate is excreted through the urine.

What role does parathyroid hormone play on phosphate reabsorption?

1. Inhibits renal tubular cell reabsorption of Ca2+ allowing it to be excreted in the urine.
2. Inhibits phosphate reabsorption by the kidney tubules

What are the effects of calcitonin on the kidney?

in response to low blood calcium levels

When is PTH released?

the kidney

What produces calcitriol?

1. decreases the expression of phosphate transporters in kidneys and the intestines
2. decreases calcitriol synthesis
3. decreases serum phosphate levels

What is the role of fibroblast growth factor 23?

1. increases calcium, magnesium, and phosphate absorption in the gut and reabsorption in the kidney
2. stimulates calcium transport into the cells
3. enhances bone formation

What are the roles of calcitriol?

in response to high levels of calcium in the blood

When is calcitonin secreted?

by parafollicular cells of the thyroid gland

Where is calcitonin produced?

PCT

Where is most phosphate reabsorbed?

Na+/PO4 exchangers

How is phosphate transported across the apical membrane?

in bones

Where is most of the magnesium in the body?

in the thick ascending limb of the Loop of Henle

Where is most of magnesium reabsorbed?

expressed in the human thick ascending limb tight junctions and seems to play a role in the control of magnesium and calcium reabsorption

What is paracellin 1?

A. increased calcium reabsorption

What is the effect of PTH on the kidney?
A. increased calcium reabsorption
B. increased phosphate reabsorption
C. increased GFR
D. decreased GFR
E. decreased calcitriol synthesis

C. g protein receptor

The PTH receptor is a ____________.
A. transcription factor
B. tyrosine kinase
C. g protein receptor
D. ion channel
E. guanylate cyclase

A. increase cAMP

PHT act at the PTH receptors on the kidney cells to ________, which produces an increase in calcitriol synthesis.
A. increase cAMP
B. decrease cAMP
C. activate phospholipase C
D. increase FGF23

B. a steroid

Calcitriol is best described as __________.
A. an amine
B. a steroid
C. a protein
D. an ecosanoid
E. a cannabinoid

A. transcription factor

The vitamin D receptor is a ___________.
A. transcription factor
B. tyrosine kinase
C. g protein receptor
D. ion channel
E. guanylate cyclase

300 mOsm/L

Bowman's Capsule

100 mOsm/L

Distal Tubule

1200 mOsm/L

Loop of Henle

100 mOsm/L with no ADH

Collecting Duct

1200 mOsm/L with ADH

Collecting Duct

1. 0% if the kidney is healthy and sugar intake is normal

5. 100 All creatinine should be cleared if the kidney is functioning properly because it is not reabsorbed.

4. 40% since more urea is reabsorbed than secreted

5. 100% I believe this is the answer because PAH is not reabsorbed. I'm not positive though.

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