Renal Module 2 Flashcards
What substances are NOT normally filtered in glomerulus in a healthy individual?
- RBCs
- Most proteins/peptides
What are the glomerular filtration layers (and size, if applicable)?
- Fenestrated endothelium (pores approx. 70-90 nm)
- Basement membrane
- Podocytes (epithelium, filtration slits approx. 25 nm)
How does the RBC/WBC size compare to glomerular pores?
RBC/WBCs are approx. 100-300x larger than the pore size
How does the glomerular basement membrane filter?
- Physically: 4-8 nm can pass through easily, 8+ nm are blocked
- Membrane charge (negative): repels small molecules that could physically go through but have a negative charge
How is albumin normally filtered out of glomerular basement membrane?
Albumin is 7 nm so it could physically get through BUT it has a negative charge so it is repelled by the membrane
What is proteinuria and how does it occur?
- Excess levels of protein in urine
- Loss of glomerular basement charge or size barrier, PCT damage
What is hematuria and how does it occur?
- Blood in the urine
- Sign of glomerular capillary disease as well as other kidney pathologies
- Often a/w inflamm condition of kidney
What is oliguria?
Low urine output/production
What is azotemia?
Elevated BUN and serum Cr
What is the MC finding of nephritic syndrome?
Hematuria
What is the MC finding of nephrotic syndrome?
Proteinuria
Factors that determine filtration in glomerulus
- Renal blood flow
- Permeability of glomerular capillaries (50x greater than skeletal muscle capillaries)
- Size of capillary bed/mesangial cells
- Hydrostatic and osmotic pressures in glomerulus and Bowman’s capsule
How do mesangial cells affect surface area of the glomerular capillary bed?
Contraction of the mesangial cells causes a decrease in surface area (less filtration, lower GFR)
What are examples of stimuli that cause contraction of mesangial cells?
AT II, ADH, Norepi
What are examples of stimuli that cause relaxation of mesangial cells?
ANP, dopamine
Describe glomerular capillary hydrostatic pressure (including what it is opposed by)
- Major force in filtration
- 55 mm Hg “pushing into” Bowman’s space
- Decreases at end of capillary
- Opposed by hydrostatic pressure in Bowman’s
What opposes glomerular capillary hydrostatic pressure?
Hydrostatic pressure in Bowman’s capsule
Describe Bowman’s capsule hydrostatic pressure
- 15 mm Hg pushing back into glomerular capillary
- Small and fairly constant at beginning and end of capillary
Describe glomerular capillary colloidal osmotic pressure
- 30 mm Hg pulling back from Bowman’s space
- Decreases at end of capillary (which maximizes filtration)
Describe Bowman’s capsule colloidal osmotic pressure
NOT a factor in filtration unless diseased/damaged glomerular capillary
What pressure gradient does the concentration at the afferent arteriole create?
30 mm Hg gradient that is “pulling back” into glomerular capillary
What pressure gradient does the concentration at the end (efferent arteriole) create?
Concentration decreases to create a gradient that maximizes filtration into Bowman’s space
Define tubular reabsorption
Reabsorbs substances (filtrate) from tubular portion of nephron back into capillary system (peritubular capillaries)
Define tubular secretion
Secretes substances (filtrate) from capillary system (peritubular capillaries) into tubular portion of the nephron
Primary function of PCT
Reabsorption of Na
What does the PCT reabsorb?
- 60-70% of H2O and Na
- 50% urea
- 90-100% glucose, AAs, bicarb
How is Na reabsorbed from the PCT?
- Co-transport
2. Active exchange of Na+/H+ (part of mechanism to reabsorb bicarb)
How does active exchange of Na/H in the PCT affect blood or urinary acid levels?
It does NOT contribute to increased blood or urinary acid levels
Describe carbonic anhydrase inhibitors
- Block Na reabsorption in PCT
- Inhibits the Na/H mechanism
How is Na transported from PCT into peritubular capillaries?
Active transport via Na/K pump
How is glucose transported from PCT lumen into the PCT cells?
Co-transported with Na via specialized carriers
How is glucose transported from PCT cells to peritubular capillaries?
Passively via GLUT carriers
What is glucose reabsorption limited by?
Number of available GLUT carriers
Define transport maximum (TM)
Max rate a substance can be transported across a cell well
What amount of plasma glucose corresponds with transport maximum of glucose in the PCT?
350+ mg/dL
Define glucose renal threshold
- Plasma values at which glucose first appears in the urine (can’t be reabsorbed)
- 180-200 mg/dL is level of glucose dumping
What is glucose dumping and at what plasma levels does this start occurring?
- Dumping of glucose into urine (too much to reabsorb in PCT)
- 180 to 200 mg/dL is when this starts
What substances are secreted in the PCT?
H+ ions, creatinine, NH3
Functions of the loop of Henle
- Reabsorbs 25% of Na filtered in glomerulus along with other filtrate that was not reabsorbed in PCT (ASCENDING LIMB ONLY)
- Regulates osmotic state of the medullary interstitial fluid and filtrate leaving the loop (regulating urine concentration)
Where does reabsorption of Na occur in the loop of Henle?
Ascending limb only!
What is Na co-transported with?
K and Cl
What is the permeability of the descending loop of Henle?
Combination of H2O permeability and minimal Na permeability
How does osmolarity of the tubular fluid change as loop of Henle descends?
INCREASES (more concentrated)
What is the permeability of the ascending loop of Henle?
LIMITED H2O permeability with increased Na permeability
How does osmolarity of the tubular fluid change as loop of Henle ascends?
REDUCED (more dilute)
How do loop diuretics work and where?
- Inhibit Na/K/Cl co-transport mechanism in loop of Henle
- Decreases Na and H2O reabsorption
- Increases osmotic concentration (decreasing interstitial fluid)
What are side effects of loop diuretics?
- Hypokalemia (reabsorption of K is inhibited)
- Hypocalcemia (reabsorption of Ca is linked to Na reabsorption so it is decreased)
Where does the DCT begin and what is its function?
- Begins at macula densa
- Macula densa sense NaCl levels
- If high NaCl, signals afferent arteriole to constrict and slow RBF/GFR (less Na filtered)
Function of early DCT
Continue dilution of tubular fluid
*Same pattern as ascending loop of Henle
Function of late DCT
Begin process of concentrating fluid for urine output
How much Na does early DCT reabsorb?
Approx. 5%
How do thiazides work and where?
Inhibit Na/Cl co-transport in EARLY DCT
What is the MC used diuretic?
Thiazides
Side effects of thiazides
- Hypokalemia
- Hypercalcemia
- Metabolic alkalosis
What is often used in conjunction with thiazides to “offset” potassium loss?
K+ sparing diuretic
What cell types are located in both late DCT and collecting duct?
- Principle cell (reabsorbs Na and H2O, secretes K)
- Alpha intercalated (secretes H)
Location and function of alpha intercalated cells?
- Late DCT and collecting duct
- Secrete H ions
Location and function of principle cells?
- Late DCT and collecting duct
- Reabsorb Na and water
- Secrete K
How and where does the late DCT/collecting duct reabsorb Na?
- Occurs in principle cells
- Aldosterone stimulates Na reabsorption and K secretion
How do K+ sparing diuretics work?
- Inhibit K secretion from principle cells in late DCT/collecting duct
- Antagonizes aldosterone influence
- Often used w/thiazides
How does the late DCT/collecting duct reabsorb water?
If ADH is present, principle cells increase permeability to water
Where is H+ secreted into late DCT from?
Intercalated cells
How does the late DCT/collecting duct contribute to acid-base regulation?
- H+ is secreted into late DCT lumen from intercalated cells
- H+ then combines with non-bicarb buffers in 2 pathways
- Based on pathway, either ammonium or monobasic phosphate is formed to be excreted in urine
- “New” bicarb is also created and reabsorbed into peritubular capillaries
2 pathways of H+ combined with non-bicarb buffers in late DCT?
- H combined with ammonia to form ammonia (excreted in urine)
- H combined with dibasic phosphate to form monobasic phosphate (excreted in urine)
Functions of collecting duct
- Determines final concentration of urine
2. Influences acid-base balance
Fluid concentrations in the nephron: PCT, loop of Henle, DCT, collecting duct?
- PCT = 300
- Start of loop = 300
- Descending limb = 1200
- End of loop = 100
- DCT = 100-150
- Start of collecting duct = 150
- End of collecting duct = 1200
In the healthy kidney, how much H2O is reabosrbed?
98.7 to 99.7%
