Renal Module II Flashcards
The glomerulus filters everything into Bowman’s space except what?
RBC/WBC, most proteins & fats
What happens if albumin and other proteins manage to get through glomerular filtration?
PCT will reabsorb proteins/albumin back into blood so they will not be excreted in urine
How much plasma is filtered into the nephrons each day? What is the body’s total plasma volume? How may times do the kidneys filter body’s total plasma volume each day?
filtered each day: 180 L
total body: 3 L
Kidneys filter total plasma volume 60 times a day
What is the urine output each day?
1-2L/day (kidneys reabsorb 178-179 L/day)
*kidneys must decide what is necessary to keep (reabsorb) in order for the body to be healthy vs. excreting
How much reabsorption happens in the PCT?
60-90% of everything that was filtered
What is reabsorbed by the PCT?
Glucose (100% reabsorbed)
Sodium, potassium, calcium, etc.
Bicarbonate
Urea
Amino acids/proteins that made it through filtration
What is secreted by the PCT?
Creatinine
Urea, ammonia
H+
Meds/drugs
Uric acid
Are there any significant dilute/concentration changes in the PCT?
No
What does the descending limb of the loop of Henle reabsorb?
Water
What does the descending limb of the loop of Henle secrete?
Urea (plays role in urine concentration gradients)
Are there any significant dilute/concentration changes in the descending limb of the loop of Henle?
Yes, concentrates tubular fluid
What does the thick ascending limb of the loop of Henle reabsorb?
Sodium, potassium, chloride
What does the thick ascending limb of the loop of Henle secrete?
Nothing
Are there any significant dilute/concentration changes in the thick ascending limb of the loop of Henle?
Yes, dilutes tubular fluid
What does the early DCT segment reabsorb?
Sodium, calcium
What does the early DCT segment secrete?
Nothing
Are there any significant dilute/concentration changes in the early DCT segment?
Yes, dilutes tubular fluid
What does the late DCT segment reabsorb?
Water, sodium, bicarbonate, urea
What does the late DCT segment secrete?
H+, potassium, ammonia
Are there any significant dilute/concentration changes in the late DCT segment?
Yes, concentrates tubular fluid
What is the central force in driving PCT reabsorption?
Sodium/potassium pump: actively pumps sodium from PCT cell into plasma
What follows sodium in the sodium potassium pump of the PCT? Why does this happen?
Water, glucose, amino acids, calcium, chloride, bicarbonate, phorphate, etc. into plasma
Because of osmotic gradient and/or cotransporters
PCT reabsorbs how much glucose & amino acids?
100%
PCT reabsorbs how much bicarbonate?
80-90%
PCT reabsorbs how much water, sodium, potassium, and chloride?
65%
PCT reabsorbs how much urea?
50%
Pathway for PCT to reabsorb water?
Na+ concentration gradients formed by active sodium/potassium pump promote water diffusion (osmosis) into bloodstream
What structures of the PCT cell allow for osmosis of H2O into the PCT cell/plasma?
Aquaporins
What further promotes ion reabsorption in the PCT?
Increased concentration of tubular fluid
How does the PCT create Na+ concentration gradients?
At the basolateral membrane, Na+ is pumped into interstitial space by sodium/potassium ATPase (potassium pumped into cell)
*active transport of Na+ creates concentration gradients
How do lipid-soluble substances diffuse across the PCT membrane?
transcellular route
How do various ions (Cl-, Ca2+, and K+) and urea diffuse across PCT membrane?
paracellular route
What is the major regulator of extracellular fluid volume (ECF)?
NaCl balance
Early PCT pathway for sodium reabsorption?
Sodium reabsorption is coupled with many filtrates (glucose, amino acids, etc.), and H+ secretion
Late PCT pathway for sodium reabsorption?
Sodium is reabsorbed w/ chloride as NaCl, also reabsorbed coupled w/ H+ scretion
What influences Na+ reabsorption in the PCT?
Hormones
What are the stimuli which increase NaCl reabsorption in the PCT?
Angio II, endothelin, smpathetics
What are the stimuli which decrease NaCl reabsorption in the PCT?
Natriuretic peptides (ANP, BNP, etc.)
What is necessary for reabsorption of bicarb in the PCT?
Na+/H+ exchange
Pathway for Bicarb reabsorption in the PCT?
-H+ secreted into lumen of cell, and Na+ goes into PCT cell
-H+ combines w/ filtered HCO3- to form carbonic acid (H2CO3)
-Carbonic acid dissociates into H2O and CO2 by carbonic anhydrase
-CO2 diffuses into the PCT cell where it will reform to carbonic acid –> dissociates into HCO3- and H+
*HCO3- reabsorbed back into blood stream
*H+ secreted back into lumen by Na+/H+ exchange
What inhibits bicarbonate reabsorption in the PCT?
Diuretics (carbonic anhydrase inhibitors)
What happens in the PCT if diuretics present?
-Filtered bicarb, sodium, and sodium chloride remain in lumen and tubular concentration increases
-Water stays in lumen due to less Na+ reabsorption/increased tubular fluid conc.
Net result: diuresis (H2O excretion) and natriuresis (Na+ excretion), along w/ bicarb excretion
Diuretics effect on acid-base balance?
Potential disruption due to plasma bicarb decreasing/becoming more acidic and urine bicarb increasing/becoming more alkaline
How is glucose reabsorbed in the PCT?
-Sodium-glucose cotransporters (SGLT 1/2): mediate Na+ and glucose cotransport into PCT cell
-Glucose transport carrier (GLUT 2): allows glucose to flow from PCT cell to bloodstream
Glucose transport in the PCT is limited by what?
of available cotransport carriers
What happens to the PCT if there is too much glucose in the plasma/hyperglycemia?
PCT cannot keep up with reabsorption and “glucose dumping” begins to occur
What are SGLT2 inhibitors?
Hypoglycemic medications that inhibit reabsorption of glucose to treat diabetes
What is the secondary benefit of SGLT2 inhibitors?
Antihypertensive benefit: inhibit sodium reabsorption/promote natriuresis and diuresis
What is the glucose transport maximum in the PCT?
Maximum rate a substance can be transported across PCT cell wall
What plasma glucose levels correspond with transport maximum of glucose in the PCT?
350 mg/dL
What is the glucose renal threshold (diabetes/hyperglycemia)?
Plasma values when glucose first appears in the urine (glucose dumping)
At what plasma glucose levels does glucose dumping begin to occur in urine?
180-200 mg/dL
What does the PCT secrete?
H+, small amount of creatinine, urea, ammonia/ammonium, meds/drugs, uric acid
How much H+ is secreted by the PCT?
Large amounts of H+ ions secreted when reabsorbing bicarbonate
How is there no net loss of H+ ions from the PCT?
The H+ ions get recycled
When does H+ secretion/excretion occur?
“Later” in the cells of the late DCT segment/collecting duct
How is creatinine formed?
Metabolic breakdown of creatinine phosphate in muscle, produced by body at a predictable rate
How is creatinine filtered through the glomerulus?
Freely
Is creatinine reabsorbed in the nephron?
No
How much creatinine is secreted in the PCT?
A small amount
How is ammonia/ammonium secreted by the PCT?
Using a process called ammoniagenesis:
-Glutamine enters PCT cell from plasma and from filtered glutamine in lumen
-PCT cell converts glutamine into ammonium (NH4+) and bicarb (HCO3-)
-Ammonium is secreted into lumen and newly formed bicarb is absorbed into plasma
Ammonium is eventually excreted from the nephron as part of what?
Acid-base regulation
What is acute tubular necrosis (ATN)?
Nephron obstruction due to cell damage of PCT and other regions of nephron (may lead to necrosis if severe)
What is acute tubular necrosis (ATN) caused by?
-Ischemia (hypotension/hypovolemic states)
-Toxins (drugs such as aminoglycosides, sulfa drugs, acyclovir, etc.)
-Endotoxins (myoglobin and hemoglobin
-Sepsis
What do ischemia/toxins cause in ATN?
Acute kidney injury (cell damage to PCT and other regions)
Breakdown of epithelial cells–>form casts/possible nephron obstruction
Urinalysis for ATN?
Muddy brown appearing urine from casts of epithelial cells
Treatment for ATN?
Focused on underlying cause, prognosis dependent on underlying condition
Loop of Henle has a critical role in what?
Regulating urine concentration
How does the descending loop of Henle concentrate the filtrate?
Reabsorbs water & leaves behind electrolytes in descending loop lumen
*osmolarity of tubular fluid increases as it descends in loop
How does the thick ascending loop (TAL) of Henle dilute the filtrate?
Reabsorbs sodium & other electrolytes
*osmolarity of tubular fluid decreases in the TAL
Urine concentration in the PCT?
300 mOsm
Urine concentration in the start of the loop of Henle?
300 mOsm
Urine concentration in the descending portion of the loop of Henle?
Gradual increase to 1,200 mOsm at the bottom
Urine concentration in the thick ascending portion (TAL) of the loop of Henle?
Gradual decrease to 100-200 mOsm
Urine concentration in the early DCT segment?
Continues to dilute: 100 mOsm
Urine concentration in the late DCT segment?
Begins to concentrate: 150 mOsm
Urine concentration in the start of the collecting duct?
150 mOsm
Finished urine concentration in the collecting duct?
Concentrated: 1,200 mOsm
or
Diluted: 100-200 mOsm
*dependent on the body’s needs
Is the descending limb permeable to water?
Yes - allows water to be reabsorbed, but not sodium/other electrolytes
What reabsorption does the narrow portion of the ascending limb of the Loop of Henle?
Passive sodium/chloride reabsorption
What does the thick ascending limb (TAL) of the loop of Henle reabsorb?
Na+, Cl-, K+ and other electrolytes (HCO3-, Ca2+, Mg+)
What is Na+ co-transported with in the thick ascending limb (TAL) of the loop of Henle?
Chloride (Cl-) and K+
What does co-transport of Na+/Cl-/K+ create in the TAL of the loop of Henle?
Electrical potential gradient that promotes passive diffusion of Na+, K+, Ca2+, Mg2+
The TAL reabsorbs how much of filtered sodium/filtered bicarb?
25% of sodium
20% of bicarb
Is the TAL of the loop of Henle permeable to water?
No - water remains in the TAL lumen and osmolarity decreases/dilutes as fluid ascends
What do loop diuretics inhibit?
Na+/K+/Cl- co-transport in the TAL
Also inhibit calcium reabsorption
Reduced sodium reabsorption in the TAL due to loop diuretics promotes what?
Diuresis, Natriuresis, Potassium excretion (potential for hypokalemia)
What can be used to offset potassium loss in the TAL?
Potassium sparing diuretics or potassium supplementation
What is a potential risk of loop diuretics inhibiting Ca2+ reabsorption?
Hypocalcemia
What can be used as a potential treatment for hypercalcemia ?
Loop diuretics and IV saline fluids
(Loop diuretics inhibit Ca2+ absorption)
Is the early segment of the DCT permeable to water/sodium?
Not permeable to water, but permeable to sodium (continues to dilute tubular fluid by allowing Na+ to be reabsorbed/leaving water in lumen before it enters late DCT)
How much filtered sodium is absorbed in the early segment of the DCT?
~5%
How is sodium transported in the early DCT?
From lumen to DCT cell by NaCl co-transport mechanism
How much filtered calcium is absorbed in the early DCT?
~10%
What stimulates calcium reabsorption in the early DCT?
PTH and estrogen
What do thiazide diuretics inhibit?
Na/Cl co-transport in the early DCT,
promote diuresis and natriuresis
What can thiazide diuretics potentially cause?
Hypercalcemia (disrupt calcium reabsorption), Hypokalemia, metabolic alkalosis
How can thiazide diuretics potentially cause hypokalemia and metabolic alkalosis?
Due to blocking of the NaCl co-transpoter in the early DCT, the Na+/K+/H+ exchange which occurs further down in late DCT/CD is disrupted (sodium increase in late DCT promotes sodium reabsorption)
*causes potassium secretion and hydrogen secretion
What may be used w/ thiazide diuretics to offset potassium loss?
K+ sparing diuretics
How do K+ sparing diuretics work?
Inhibit K+/Na+ exhange in late DCT/CD –> less K+ secretion and less sodium reabsorption
Functions of the late DCT/CD?
-Regulate final urine conc. (urea resorption, Na+/water resorption)
-Regulate acid-base homeostasis
-Regulate potassium homeostasis
Two types of cells in late DCT/CD?
Principal cells and intercalated cells
Role of principal cells in late DCT/CD?
Reabsorb sodium and water, secrete potassium
Role of Type A intercalated cells (A-IC) in late DCT/CD?
During acidosis: secrete H+ ions and reabsorb HCO3- and K+
*maintenance of acid-base homeostasis
Role of Type B intercalated cells (B-IC) in late DCT/CD?
During alkalosis: reabsorb H+ ions and secrete HCO3- and K+
*maintenance of acid-base homeostasis
What stimulates principal cells of late DCT/CD to reabsorb sodium and secrete potassium? How?
Aldosterone
Stimulates Na+/K+ pump to:
-transport sodium from DCT/CD cells into bloodstream
-transport potassium from bloodstream into DCT/CD cells
What can inhibit aldosterone and therefore inhibit K+ secretion/Na+ reabsorption from principle cells in the DCT/CD?
K+ sparing diuretics
What stimulates principal cells of late DCT/CD to reabsorb water?
ADH
What are aquaporins? What is the effect of ADH on aquaporins?
Openings located on cell membrane of late DCT/CD that allow water to diffuse into DCT/CD cells and plasma
ADH stimulates expression of aquaporins in principle/intercalated cells
Water reabsorption in late DCT/CD is regulated by what?
Sodium concentration gradient established by principal cells:
if aldosterone present- Na+ into principle cell/plasma
if ADH present- aquaporins allow water to flow into principle cell/plasma
Amount of secretion of H+ and absorption of HCO3-/K+ that occurs in late DCT/CD depends on what?
Acid-base status of plasma
How do type A intercalated cells (A-IC) regulate acid-base balance in late DCT/CD?
Very active in regulation of H+, HCO3-, K+ when plasma is acidotic
How do type B intercalated cells (B-IC) regulate acid-base balance in late DCT/CD?
Very active in regulation of H+, HCO3-, K+ when plasma is alkalotic
Mechanism of Type A intercalated cells in acidosis?
Cell forms cabonic acid that dissociates into CO3- and H+
–> H+ secreted into lumen (decreases plasma H+, raises plasma pH)
–>HCO3- is reabsorbed into plasma (raises plasma pH, buffers the acidosis)
How is hyperkalemia associated with acidosis?
Kidneys: type A cells promote potassium reabsorption
Tissues/ECF: H+ flows into cells, K+ flows out of cells into plasma
Mechanism of Type B intercalated cells in alkalosis?
Cell forms cabonic acid that dissociates into CO3- and H+
–> H+ is reabsorbed into plasma (increases plasma H+, lowers plasma pH)
–>HCO3- is secreted into lumen (decreases plasma bicarb, lowers plasma pH, buffers the alkalosis)
How is hypokalemia associated with alkalosis?
Kindeys: Type B cells promote K+ secretion
How much filtered sodium is reabsorbed in the PCT?
67%
What inhibits HCO3- reabsorption in the PCT?
Carbonic anhydrase inhibitors via the Na+/H+ pathway
Is sodium reabsorbed in the descending limb of the loop of Henle?
No
How much sodium is absorbed in the ascending limb (TAL) of the loop of Henle?
25%
How much sodium is reabsorbed in Early DCT?
5%
How much sodium is absorbed in late DCT/CD?
3%
How much potassium is reabsorbed in the PCT?
60-70%
Is potassium reabsorbed in the descending limb of the loop of Henle?
No
How much potassium is absorbed in the ascending limb (TAL) of the loop of Henle?
25%
Is potassium reabsorbed in early DCT?
No
Which cells secrete potassium via sodium/potassium pump in the late DCT/CD?
Principal cells
Which cells have a sum of potassium activity that has less effect compared to principle cells, yet can still alter potassium homeostasis?
Intercalated cells: Type A & B
Rough rule of thumb for acidosis?
Promotes K+ reabsorption (Type A cells)
*Hyperkalemia and acidosis
Rough rule of thumb for alkalosis?
Promotes K+ secretion (Type B cells)
*Hypokalemia and alkalosis
The liver breaks down ammonia (toxic) to what nontoxic product?
Urea
The kidney uses urea for what?
Regulation of concentration gradients in renal medulla necessary for maintaining urine concentration
Where is 50% of urea passively reabsorbed?
PCT
Where is urea secreted?
Descending limb of loop of Henle
Where is urea reabsorbed, and where does ADH increase permeability of urea?
Reabsorbed in late DCT/CD
ADH inc. permeability of urea in CD
How much total urea is excreted?
30-50% of filtered load
What does the BUN test measure?
Amount of urea nitrogen in plasma
What would a high BUN indicate?
Kidney pathology that decreases GFR (causing urea to accumulate in blood)
What is azotemia?
High nitrogen in the blood
What would a low BUN indicate?
Liver pathology that decreases urea synthesis
What does the BUN/creatinine ratio compare?
BUN with serum creatinine
Normal BUN/creatinine ratio?
Between 10:1 and 20:1
What would a high BUN/creatinine ratio indicate?
Kidney pathology that decreases GFR or pathologies that decrease blood flow to kidneys
(ex. shock- not enough pressure to push blood through kidneys)
How does the BUN/creatinine ratio still appear high when both BUN and creatinine increase?
Creatinine will still be secreted into PCT despite low GFR, so BUN will increase “more” than creatinine in blood
Net result: increased BUN/creatinine ratio
What would a low BUN/creatinine ratio indicate?
Liver pathology or rhabdomyolysis (skeletal damage/necrosis)
In which low BUN/creatinine ratio disease will BUN decrease, while creatinine remains the same?
Liver pathology - synthesis of less urea while creatinine is still synthesized at same rate from the muscle
In which low BUN/creatinine ratio disease will BUN remain the same, while creatinine increases?
Rhabdomyolysis - liver synthesizes same amount of urea while excess muscle breakdown releases excess amounts of creatinine into the plasma
