FINAL Exam Flashcards
What is secreted in the PCT?
Organic anions and cations including:
Drugs and their metabolites
Creatinine
urate
What is the TF/P ratio of inulin?
Why?
3
bc water is being lost with NO change in the solute [ ]
TF/P ratio of glucose?
Why?
0
Bc all solute (glucose) is avidly reabsorbed
TF/P ratio of PAH
Why?
10
Bc water is being lost AND PAH is being secreted back into the tubular lumen
What provides the major driving force for reabsorption of water and other solutes?
PCT Na+ reabsorption
What happens to Cl and urea as Na and water are reabsorbed?
They become more concentrated in the luminal fluid
Is paracellular reabsorption of Cl and urea in the early PCT active or passive process?
Why?
Passive
Due to the modest [ ] gradient bw lumen and peritubular interstitium
What systems regulate plasma concentrations of glucose and amino acids?
Liver and endocrine
What is the basic mechanism of glucose and amino acid reabsorption?
Secondary active transport
Trans cellular only
How do glucose and amino acids exit the cell once inside?
Via facilitated diffusion through the basolateral membrane
What does it mean if glucose appears in the urine?
What is a disease in which this happens?
The sodium glucose transporters are fully saturated
Diabetes
Filtered load = ?
GFR x Pglucose
Why does urine output increase with diabetes?
Hint: think about glucose
More glucose is trapped in the tubular lumen creating a higher osmolarity. This forces water to be pulled back from the cell into the tube thus increasing the urine output
What are the consequences of osmotic diuretics?
INC water excretion
INC sodium excretion (lose salt with the water to maintain the osmotic gradient)
What are the organic anions?
What kind of transport in the PCT do they utilize?
PAH, bile salts, uric acid, creatinine
Tertiary Active Transport
What drugs use tertiary active transport?
Penicillin, Salicylates, anti-viral drugs
What factors promote fluid movement INTO the peritubular capillaries (2)?
High plasma colloid osmotic pressure (pi c)
Low hydrostatic pressure (Pc)
Name the 3 steps in tertiary transport of organic anions:
- Na/K ATPase creates a gradient that helps to bring sodium IN with sodium dicarboxylate anion carrier and AKG
- Once inside the cell, AKG is exchanged for OA- via countertransport
- OA- is transported from the cell to the tubular fluid via another AKG countertransport and through a OA- transporter
What kind of molecules are membrane permeable?
Non-polar, lipid soluble molecules –> aka UNCHARGED
What kind of pH generates neutral acids and bases?
Acid: low pH
Base: high pH
Does luminal acidification favor reabsorption or secretion of organic acids?
Why?
Reabsorption
Because acidic lumen neutralizes organic acid and thus it can traverse membranes
If a patient overdoses on aspirin, how can you promote urinary excretion of it to help leave the body?
Inject bicarbonate into patient to alkalinize the urine. This makes the lumen basic and the aspirin will remain charged and stuck in the lumen to be excreted
What is the main substance exerting osmotic pressure in cells?
Interstitial fluid?
K+
Na+
What does increased Na+ in the body do?
What may the compensating for?
Expands the ECF and the ECV
hypovolemia
How is plasma Na (therefore osmolarity) regulated?
Water balance
What factors promote Na reabsorption?
Sympathetics
RAAS
Secretion of aldosterone
What factors promote Na excretion?
ANP
BNP
Urodilatin
Intrarenal PGs
How do PGs promote Na excretion?
They vasodilate, thus Increasing RBF, Increasing filtration and Increasing filtered load of Na+
What does constriction of efferent renal arteriole do to GFR and RBF?
slightly increase GFR
Decrease RBF
Where is primary site of AGII action and what does it do?
Where is the secondary site?
PCT
Na reabsorption via INCreasing Na-H exchanger activity (pump out H+ and bring Na+ in)
TAL, CD
What does AGII stimulate?
Thirst
ADH secretion from posterior pituitary
Aldosterone secretion from adrenal cortex
What are the main Renal effects of AgII?
DEC RBF
DEC medullary blood flow
INC tubular sodium reabsorption
Where does aldosterone act?
Late DCT and principal cells in CD
What does aldosterone primarily do?
Secondarily?
K+ secretion by principal cells
Na+ reabsorption via epithelium Na+ channels
What effect does aldosterone have on H+?
Stimulates H+ secretion via INCreased activity of ATPase in intercalated cells
Hyperaldosteronism leads to what?
Hypokalemia
Metabolic Alkalosis
What 3 factors control aldosterone secretion aka cause a release of aldosterone?
INC plasma [K+]
INC plasma [ACTH]
Hypovolemia
What are the main effects of ANP?
INcrease Na+ and water excretion
What does ANP do to GFR?
How?
INCREASES GFR
Dilates afferent arterioles, constricts efferent arterioles
What secretes urodilatin?
In response to what?
DCT and CD
INC arterial pressure and ECF volume
What does urodilatin suppress?
What effect does it have on systemic circulation?
Na and water reabsorption by medullary CD
NO EFFECT
What do intrarenal PGs (PGE2) do Na excretion and GFR (via what mechanisms)?
INCrease Na excretion by suppressing Na reabsorption in TAL and CD
INCrease GFR by dilating renal arterioles
What secretes ADH?
Hypothalamus via posterior pituitary
What are the 2 major stimuli for ADH release?
Hyperosmolarity
Volume depletion
What osmoreceptors are most important?
Hypothalamic > hepatic
What is the luminal potential in the PCT?
TAL?
DCT?
+/- 2
+6 to +10
-70
What is the major mechanism of sodium reabsorption in the PCT?
Cotransport with glucose, a.a., phosphate
Countertransport with H+ (Na/H+ exchange)
Mechanism of sodium reabsorption in TAL?
Na, K, 2Cl cotransport
Mechanism of sodium reabsorption in early DCT?
Na, Cl cotransport
mechanism of sodium reabsorption in late DCT, CD?
Luminal Na membrane channels inserted by aldosterone
What is the descending limb of the loop of Henle permeable/impermeable to?
Perm - water
Impermeable to Na and Cl
What is the ascending limb perm/impermeable to?
What is this part called?
Impermeable to water
diluting segment
What is responsible for the +6mv potential in the TAL?
K+ leak channels
What ions are repelled by the + luminal potential and are able to leave the lumen paracellularly?
K+, Mg2+, Ca2+
Where is the major site of control of salt and water balance?
Late DCT and CD
What does aldosterone stimulate in late DCT and CD?
Na+ reabsorption
K+ and H+ secretion
What does ADH stimulate in the Late DCT and CD?
Water reabsorption
What is responsible for the large negative potential in the DCT?
What does this drive?
Cl-, it cannot get through tight junctions
K+ and H+ secretion by the principal cells
What is the MOA for aldosterone and Na+ reabsorption in the principal cells?
Aldosterone translocates to the nucleus of principal cells and helps it transcribe the proteins that are inserted into the apical membrane (ENaC) allowing Na to enter the cell
How does ADH increase the water permeability of the late DCT and CD?
ADH attaches V2 receptor to basolateral membrane of the cell via cGMP which will insert aquaporin channels onto the luminal side of the membrane
Why does the inner medullary interstitial fluid have a high solute concentration?
Low blood flow in inner medulla allows for concentration of solutes
What comprises the countercurrent multiplier system (3)?
Descending and ascending loops of Henle
Vasa recta
CDs
What is responsible for half of the 1200 mOsm gradient?
Na, K, Cl cotransporter in TAL
What promotes urea reabsorption from the inner medullary CD?
ADH
If you have a high protein diet, what is your urine concentrating ability like?
INCreased
What is special about the vasa recta?
VERY slow blood flow
What is antidiuresis?
Dehydrated patient
Therefore reduction in excretion of urine
What is the urine like in an antidiuresing patient?
Low volume, high concentration
Due to presence of ADH
What is happening in a patient who is diuresing?
Volume expanded
Low ADH
What is the urine and concentration of the medullary interstitium like in a patient who is diuresing?
high volume of dilute urine excreted
Lower solute concentrations in the medullary interstitium
How much waste is generated per day?
What is the max urine concentration?
600
1200
Osmolar clearance equation =
(Uosm x V) / Posm
What happens when the kidneys excrete excess solutes?
Osmolar clearance Increases
Free water clearance (C) = ?
V - Cosm
If Uosm
Free water clearance is positive and pure water is cleared from the body (getting rid of water)
What does Uosm > Posm mean?
Free water clearance is negative and the body will retain pure water
Ie. Cases of dehydration
How does ADH affect free water clearance?
Decreases it bc you are reabsorbing more water
Fractional excretion = ?
Amount excreted / amount filtered
Fractional excretion condensed formula =
(Ux X Pcr) / (Px X Ucr)
If FE is below 1% what does it mean?
Prerenal and AGN
Sodium is avidly reabsorbed
If FE is greater than 2% what does it mean?
Acute Tubular Necrosis (ATN), volume expanded or Renal cause
Na is excreted
What does the PCT reabsorb?
Filtered water Na K Cl Bicarbonate Ca Phosphate All the glucose and a.a.
What are the 3 causes of pseudohyponatremia which lead to errors in lab measurement of Na?
Hyperproteinemia
Hyperlipidemia
Hypercholesterolemia
What are the 2 causes of pseudohyponatremia due to dilutional hyponatremia?
Hyperglycemia Unmeasured osmosis (antifreeze)
Plasma solute concentration = ?
2xNa + glucose/18 + BUN/2.8
Osmolar gap =?
What is normal?
Difference between estimated plasma osmolarity and true measured plasma osmolarity
Less than 10
What are the causes for true hyponatremia (low sodium and low plasma osmolarity) in cases of dilute urine and low ADH?
Reset osmostat (pregnancy) Psychogenic polydipsia
A Uosm/Posm
Primary polydipsia
Neuro(central) OR Nephro Diabetes Insipidus
What does a Uosm/Posm > 1 indicate with a low plasma osmolality?
High plasma osmolality?
SIADH
Dehydration
How do you differentiate between Nephro and Neuro DI?
Give ADH
If the [urine] Increases and the problem is corrected, then it is Neuro
If giving ADH has no effect and does not fix the problem, then Nephro
will the ADH level be low or high in a patient with Neuro DI?
Low
What are 2 causes of hypernatremia (Na > 145)?
Extra renal water loss (excessive sweating, fever, diarrhea, vomiting)
Renal water loss (ADH not working properly)
How does lithium act in the body?
What is a result of lithium in the body?
Limits V2 receptors from making cAMP, therefore less ADH and less transcription of aquaporin channels
Result is Nephro DI
What are 2 common causes for Nephro DI?
Hypercalcemia (assoc. with malignancies)
Hyperkalemia (assoc. with acidosis)
What are some common causes for central DI?
Head trauma
Postpartum hypophysitis (autoimmune)
Hypothalamic or pituitary tumor
What maintains a normal BP while being volume expanded?
Initial INC in ECF volume activates atrial volume receptors that stimulate ANP secretion to return ECF volume to normal
What are some causes of SIADH?
Pulmonary tb CHF CNS issues (stroke) Intubation w/mechanical ventilation Drugs (SSRI, cyclophosphamide, Tegretol)
What are some ADH antagonists?
Conivaptin
Demeclocycline
What is common cause of hypervolemia?
What happens?
CHF
Excessive gain of salt and water –> edema
What does a BUN > 20 indicate?
Pre-renal cause
Hypovolemia
What are signs of Hypovolemia?
Orthostatic hypotension
Orthostatic tachycardia
Loss of skin turgor
Dry mucous membranes
What are hyperkalemia patients at risk for?
Acidosis
Are diabetics at risk for hypo or hyperkalemia?
Why?
Hyperkalemia bc lack of insulin to bring potassium from the plasma into the cells
Where is the major site of K+ regulation?
CDs
Who is K+ reabsorbed in the nephron?
67% PCT paracellularly
20% TAL via Na,K,2Cl cotransport
How does a higher flow rate affect the secretion of K+?
More dilute tubular fluid, therefore more secretion of K+ into the tubule
How do most diuretics affect Na, volume and K+?
Increase Na and volume to late DCT and CD, which increases K+ secretion
What does increased plasma [K+] stimulate?
Aldosterone secretion
What is Conn’s disease also called?
What causes it?
Primary hyperaldosteronism
Aldosterone secreting tumor in adrenal cortex
What is a result of Conn’s disease?
Hypokalemia
Metabolic alkalosis
What is Addison’s disease also called?
What causes it?
Hypoaldosteronism
Destruction of adrenals and aldosterone isn’t secreted
What is the result of Addison’s disease?
Hyperkalemia
Acidosis
What are hypokalemic patients at risk for?
Alkalosis
What do diuretics do and how do they work?
Increase urine excretion by inhibiting tubular solute and water reabsorption
When do you use a diuretic?
When volume expanded (CHF, edema)
Where do osmotic diuretics work?
Give example of one
How does it work?
PCT
Mannitol
Inhibits water reabsorption and secondarily Na
Where do CA inhibitors work?
Give example
How?
PCT
Acetazolamide
Inhibit NaHCO3 reabsorption
What are some examples of loop diuretics?
furosemide
Ethacrynic acid
Bumetanide
How do loop diuretics work?
What do they do to total RBF?
Inhibit Na,K,2Cl cotransporter by competing for Cl
Increase RBF and dissipates high solute [ ] of medullary interstitium
What do loop diuretics do to the descending limb of loop of Henle?
Lessens the water reabsorption therefore decreasing the concentrating ability or our urine
Where do thiazide diuretics act?
Example
How?
Result?
DCT
HCTZ
Inhibit Na,Cl cotransport
Increased Na,Cl,K excretion and decreased Ca excretion
Where do potassium-sparing diuretics work?
Example
How?
CD
Amiloride, triamterene, spironolactone
Inhibit Na reabsorption and K secretion
What is Ca2+ required for?
What can low EC Ca produce?
Neuromuscular transmission
Hypocalcemic tetany
How does calcium affect APs?
Dampen APs by blocking Na channels
What kind of calcium is biologically active?
What is the other kind bound to?
Free Calcium
Proteins (albumin)
What does acidemia do to the plasma free Ca level?
Increases amount of free plasma Ca2+
Low levels of H+ in the plasma does what to free calcium levels?
Decreased free plasma [Ca]
What happens if Ca goes down?
PTH is released by parathyroid gland to activate Vit D and Calcitriol/Vit D3 which increases absorption of calcium from your diet
Bone resorption to increase amount of calcium that is released from your bone by osteoclastic activity
Where is Calcium mostly reabsorbed?
Via what mechanism?
PCT
Transcellularly
What prevents Ca from being reabsorbed paracellularly in the DCT?
Claudin 8 (CLDN8)
Where does paracellular Ca reabsorption occur?
Because of what?
TAL
Driven by the 6mV potential
What effect do loop diuretics have on paracellular Ca reabsorption?
INC flow, abolish charge in the lumen, thus decreasing calcium reabsorption leading to hypocalcemia
What effect do thiazide diuretics have on calcium levels?
Why?
Cause hypercalcemia
Bc Na/Cl transporter is inhibited, less intracellular Na, so Na is instead exchanged via 3Na/Ca transporter that brings sodium in the cell and takes calcium into the blood
What are the 3 effects of increasing plasma PTH?
INC bone resorption
INC tubular reabsorption of calcium
INC intestinal absorption of calcium
What transporters does Phosphate use to get into the cell and eventually into the blood?
Cell: 2Na/Pi cotransporter
Blood: Pi/A- countertransporter
What does PTH do to PCT phosphate reabsorption?
How?
Inhibits phosphate reabsorption and increases the amount of phosphate excreted
Inhibits the Pi/anion countertransporter in the blood
What 3 forms is Mg carried in the plasma?
60% free
20% complexed w/inorganic or organic anions
20% bound to plasma proteins
Where is the bulk of Mg reabsorbed?
How?
TAL (63%)
Paracellular movement
What are volatile acids?
Examples
Produced by metabolic processes that can be expired by your respiratory system
Carbonic acid, H2CO3
What are fixed acids?
Examples
Non-carbonic acids generated metabolically that are excreted in the urine and cannot be removed via ventilation
Sulfuric, phosphoric, lactic, hydrochloride acids, ketone acids, protein, nucleic acid
What are the 3 lines of defense against pH changes in order and brief description of what they do?
- Chemical buffers - accept H+ ions
- Respiration - can blow off CO2
- Kidneys - gets rid of fixed acids
What is the Renal response to excess acid?
All the filter bicarbonate is reabsorbed in the PCT
H+ secreted into the lumen and is excreted as ammonium in the urine
What is the Renal response to excess base?
Incomplete reabsorption of filtered bicarbonate
Decreased H+ secretion
Secretion of HCO3- in CD
How is most H+ excreted?
Titratable acid - conjugate base of metabolic acids (phosphate, creatinine, urate)
Ammonia - MAJOR way to get rid of H+
Total renal H+ excretion = ?
Urinary excretion of titratable acid + ammonia - HCO3-
Where does the the acidification of the nephron begin?
Where does a major of the acidification occur?
Where is the major site of ammonium formation?
PCT
DCT and CD
PCT
What do alpha-intercalated cells do?
Describe the resulting blood?
What stimulates them?
Actively secrete H+ via ATPase
Alkalotic
Aldosterone
What to Beta-intercalated cells do?
Name the transporter
Secrete bicarbonate to eliminate excess base
Bicarbonate is exchanged for Cl (counter-transporter)
Hyperaldosteronism leads to what?
Alkalosis
Hypokalemia
How many H+ ions are secreted in the reabsorption of HCO3-?
ZERO
What substance is bicarbonate temporarily converted to so that it may traverse membranes freely?
What is this process dependent on?
CO2
Na/K ATPase
What is the most important buffer converted to titratable acid?
Filter HPO4(2-)
What does Glutamine produce?
What is the ultimate result?
2 ammonium ions
Acidification of the urine
What renal response occurs if there is a decrease in intracellular pH?
Means increased [H+], therefore will secrete more H+
What renal response will occur if there is increased PCO2?
Will excrete H+ ion
What renal consequences will occur if a CA inhibitor is administered?
Cannot reabsorbed bicarbonate, get metabolic acidosis
What renal response will occur if there is Increased Na reabsorption due to volume depletion?
Increase H+ secretion
What renal response will occur to hypokalemia?
Want to reabsorbed more K+ in exchange for secreting H+, therefore alkalosis
What renal response will occur if there is increased plasma aldosterone?
Increase activity of Na/K ATPase to reabsorb sodium and secrete potassium
Will also stimulate the H+ ATPase to secrete more H+ ions making the blood alkalotic
What can diuretic abuse cause?
How?
Alkalemia bc there will be INC secretion of H+ as a result of the RAAS trying to retain water
What can cause metabolic acidosis?
Gain of fixed acids
Diarrhea
What can cause metabolic alkalosis?
Alkali ingestion (seltzers) Vomiting
What does hyper choleric acidosis mean?
Anion Gap is unchanged
What does a high anion gap acidosis indicated?
Normochloremic
MUDPILES
MUDPILES mnemonic
Methanol, metformin Uremia DKA (diabetes, alcohol, starvation) Paraldehyde Iron, Isoniazid, Inhalants Lactic acidosis Ethylene Glycol Salicylates (aspirin), toluene
What are causes of metabolic acidosis with a normal anion gap?
Diarrhea
renal tubular dysfunction
CA inhibitors
Addison’s disease
