Lecture 1: Renal Physiology Review Flashcards
In which 2 compartments are protein levels the highest?
1) ICF compartments
2) Vascular compartments
What is the pressue generated by large molecules (like proteins) in solution that are impermeable to membranes?
Oncotic (colloid osmotic) pressure
Which 4 indicators can be used to measure ECF?
- 22Na+
- 125I-iothalamate
- Thiosulfate
- Inulin
How is ICF volume calculated?
TBW - ECF = ICF
Why can albumin (125I-albumin) be used to measure plasma volume?
Does not cross plasma membranes
How is interstitial fluid volume calculated?
ECF - plasma = ISF
ECF osmolality is driven (primarily) by?
Where are the concentrations of Na+ greatest between the vasculature, ICF, and interstitial fluid (rank them)?
- Na+ and Cl-
- [Na+] vasculature > [Na+] interstital fluid > [Na+] ICF
ICF osmolality is primarily driven by what ion(s)?
K+
ECF osmolality controls ______ volume
ECF osmolality controls ICF volume
All solutes that enter or leave the body do so via the?
ECF
Hypernatremia is defined as plasma [Na+] >?
plasma [Na+] > 146 mEq/L
Hyponatremia is a defined as plasma [Na+]
plasma [Na+] < 136 mEq/L
How is filtration rate calculated (equation)?
What are the components of the equation (i.e., Pc, Pi, πc, πi..)?
Filtration rate = Kf[(Pc−Pi)−σ(πc−πi)]
- Pc = hydrostatic pressure within capillary
- Pi = hydrostatic pressure of interstitial fluid
- πc = oncotic pressure of plasma
- πi = oncotic pressure of interstitial fluid
How is anion gap calculated?
Anion gap = [Na+] - ([Cl-] + [HCO3-])
When IV 0.9% NaCl (normal saline) is added to ECF what change occurs to osmolality and volume?
- No change in osmolality
- Only volume of ECF is increased
When IV 3% NaCl (hypertonic) is added to ECF what change occurs to osmolality and volume?
- Osmolality increases and pulls water from ICF into ECF
- Increased ECF volume and decreased ICF volume = cells shrink
When IV 0.45% NaCl (hypotonic) is added to ECF what change occurs to osmolality and volume?
- Osmolality of ECF decreases and water moves out of ECF into the ICF to equilibrate = cells swell
- ECF and ICF volumes BOTH increase
What is the stimulus for Angiotensin II in the kidney?
Effects on GFR and RBF?
- ↓ ECF volume = stimulus
- Causes ↓ in GFR and ↓ RBF
What are the 5 stimuli for Endothelin release in the kidney?
Effect on GFR and RBF?
- ↑ Stretch, Angiotensin II, bradykinin, epinephrine, ↓ ECF volume = stimulus
- Causes ↓ GFR and ↓ RBF
What are the 2 stimuli for release of Prostaglandins in the kidney?
Effects on GFR and RBF?
↓ ECF volume and ↑ shear = stimulus
- No change/↑ GFR and ↑ RBF
What are the 6 stimuli for NO release in the kidney?
Effects on GFR and RBF?
- Stress, shear stress, ACh, histamine, bradykinin, and ATP = stimulus
- ↑ GFR and ↑ RBF
What are the 2 stimuli for Bradykinin release in the kidney?
Effect on GFR and RBF?
- Prostaglandins, ↓ ACE = stimuli
- ↑ GFR and ↑ RBF
What is the stimulus for Natriuretic Peptides (ANP, BNP) in the kidney?
Effect on GFR and RBP?
- ↑ ECF volume = stimulus
- ↑ GFR and no effect on RBF
Caution should be taken when administering what drug to hypertensive pts, renal stenosis pts, and patients on diuretics?
NSAIDs due to interference with PGE2 —> Na+ retention
The afferent and efferent arterioles of the kidney are innervated by what neurons?
Sympathetic
Which NT’s are released by sympathetic nerves at the afferent and efferent arterioles in the kidney?
- Norepinephrine
- Dopamine
With negative Na+ balance which arterioles of the kidney constrict in response to α-adrenergic stimulation and what are the downstream effects?
- Afferent > efferent
- Afferent vasoconstriction –> reduced hydrostatic pressure in glomerular capillary lumen + decreased glomerular filtration
- Reduces GFR + filtered load of Na+ to the nephrons + increased systemic BP
What is the effect of sympathetic stimulation of the β1 receptors on juxtaglomerular granular cells?
Renin release + RAAS —> Increased BP
Reabsorption of what along the nephron is directly stimulated by α-adrenergic stimulation?
What is the most important segment of kidney influenced by sympathetic nerve activity?
- NaCl reabsorption via Na-K ATPase —> reducing fraction of filtered Na+ that is ultimately excreted
- Most important segment = proximal tubule
Increased renal sympthathetic nerve activity on the kidney is an adaptive response with what ultimate goal?
↓ net NaCl excretion and restore normal ECF volume
When Na+ balance is altered, the kidneys take several day to respond maximally to these alterations and reach a new steady state.
What changes in volume and plasma [Na+] occur during positive/negative Na+ balance?
- Positive [Na+] balance, the ECF volume expands = no change plasma [Na+]
- Negative [Na+] balance, the ECF volume contracts = no change plasma [Na+]
The combined action of which 2 segments of the nephron reabsorb approximately 92% of the filtered amount of Na+?
- Proximal tubule
- Loop of Henle
Which 2 parts of the nephron make final adjustments in Na+ excretion to maintain a euvolemic state?
- Distal tubule
- Collecting duct
During ECF volume expansion there is increased release of what from the heart and what from the kidney?
- ANP and BNP from the heart —> Increased Na+ excretion
- Urodilatin by the kidneys –> decreased collecting duct Na+ reabsorption
What are the 2 factors which lead to decreased secretion of ADH with ECF volume expansion?
- ↑ Na+ excretion, plasma osmolality begins to fall –> ↓ ADH (posterior pituitary)
- ↑ levels of natriuretic peptides –> ↓ ADH (posterior pituitary)
During ECF volume contraction, volume sensors in both the high- and low-pressure vascular circuits send signals to the kidneys that cause what 3 changes?
- ↑ renal sympathetic nerve activity
- ↑ renin secretion –> ↑ angiotensin II levels and thus ↑ aldosterone secretion by adrenal cortex
- Stimulation of ADH secretion by posterior pituitary
*Reduce NaCl and water excretion!
What is the effect of ADH on the late portion of the distal tubule and the collecting duct?
Enhances water reabsorption and stimulates limited Na+ reabsorption
What 3 factors are important in stimulating renin secretion?
- Perfusion pressure
- Sympathetic nerve activity
- Delivery of NaCl to the macula densa
Renin alone does not have a physiological funtion, how does it act and describe the series of events to follow?
- Functions as proteolytic enzyme and cleaves angiotensinogen (liver)—> angiotensin I
- Angiotensin Iis cleaved byACEfound on vascular endothelial cells (pulmonary and renal) intoAngiotensin II
What are the 2 important functions of ACE?
- Converts angiotensin I —-> angiotensin II
- Degrades bradkykinin
What are the 4 important physiologic functions of Angiotensin II?
- Stimulation of aldosterone by adrenal cortex
- Arteriolar vasoconstriction (↑ BP)
- Stimulation of ADH secretion and thirst
- Enhancement of NaCl reabsorption by the nephron
Aldosterone secretion is stimulated by what 2 things?
- Angiotensin II
- Increased plasma [K+]
Aldosterone stimulates the reabsorption of NaCl in which 3 parts of the nephron?
- Thick ascending limb
- Portions of distal tubule
- Collecting duct
What are the portions of the distal tubule and collecting duct that functionally respond to aldosterone called?
Aldosterone sensitive distal nephron (ASDN)
Upon its action on the ASDN, aldosterone causes an increase in the abdundance of which channels/transporters for Na+ reabsorption?
- Na-Cl symporter in the cells of distal tubule
- ENaC channels in apical membrane of principal cells in the late distal tubule and collecting duct
- Na-K-ATPase pump on basolateral membranes
Other than Na+ reabsorption, Aldosterone also has an effect on what 2 other ions?
- Increase in K+ excretion
- Tubular secretion of H+ thru stimulation of H+-ATPase in the apical membrane of α-intercalated cells
How is Na+ reabsorbed in the first half of the proximal tubule vs. the second half?
- First half = Na+ primarily reabsorbed w/ HCO3- + glucose, AA’s, Pi, and lactate
- Second half = Na+ reabsorbed mainly w/ Cl-
Majority of NaCl is filtered in the proximal tubule by which 2 routes?
- 2/3 move across via transcellular path
- 1/3 moves across via paracellular path
Which molecules are reabsorbed in both the descending limb and thick/thin ascending limb of the loop of Henle?
Which channels are necessary for H2O reabsorption?
- Descending = does NOT reabsorb NaCl. But H2O reabsorption occurs exclusively in some portions via AQP1 channels
- Ascending = impermeable to H2O; but can reabsorb NaCl
*Ca2+ and HCO3- are reabsorbed in loop of Henle
What can be reabsorbed in the early distal tubule of the nephron?
- Na+
- Cl-
- Ca2+
*Impermeable to H2O
Which transporter is found in the early distal tubule for reabsorption of NaCl and how do they ions leave the cell once inside?
- Na+-Cl- symporter (NCC)
- Na+ leaves cell via Na+-K+-ATPase
- Cl- diffuses thru Cl- channels
Thiazide diuretics inhibit what channel?
NCC symporter (Na+-Cl-)
Major stimulus for Angiotensin II and where are its sites of action?
What’s its effect?
- ↑ Renin = major stimulus
- Acts on PT, TAL, DT/CD
- ↑ NaCl and H2O reabsorption
Major stimulus for Aldosterone and where are its sites of action?
What’s its effect?
- ↑ Angiotensin II = major stimulus
- Acts on TAL and DT/CD
- ↑ NaCl and H2O reabsorption
Major stimulus for ANP, BNP, and urodilatin and where are its sites of action?
What’s its effect?
- ↑ ECF volume = major stimulus
- Act on the CD
- ↓ H2O and NaCl reabsorption
Major stimulus for sympathetic nerve activity in the nephron in regards to transport?
Where do they have effect?
Effect on transport?
- ↓ ECF volume = major stimulus
- Act on PT, TAL, DT/CD
- ↑ NaCl and H2O reabsorption
Major stimulus for Dopamine release in the nephron and at which sites does it act?
Effect on transport?
- ↑ ECF volume = major stimulus
- Acts on PT
- ↓ H2O and NaCl reabsorption
What are the 2 sites within the nephron where ADH can have an effect?
- DT
- CD
What causes Central Diabetes Insipidus?
How does it present?
- ↓ ADH due to either damaged pituitary or hypothalamus
- Polyuria, nocturia, and, due to the initial elevation in serum sodium and osmolality, polydipsia (very thirsty)
What is the dysfunction in Nephrogenic Diabetes insipidus?
How do these patients present?
- Kidneys unable to respond to ADH
- Pt will have polyuria, nocturia, and polydipsia
- Plasma [Na+] and osmolality are elevated, and kindeys will excrete large quantities of very dilute urine
In SIADH what will the plasma osmolarity and urine osmolarity be like?
- Hyponatremia —> ↓ plasma osmolarity w/ ↑ volume of H2O
- ↑ urine osmolarity
In adrenal insufficiency what occurs to the volume/osmolality of the ECF and ICF?
- Decreased osmolality in both compartments due to loss of Na+
- ↑ ICF volume
- ↓ ECF volume
What are 3 stimuli for renin secretion?
- Sympathetic activation via β1 receptor activation in JG apparatus
- ↓ NaCl delivery to the macula densa = NaCl sensor!
- Afferent arteriolar vasocontriction
Which 5 hormones cause afferent arteriole vasdilation?
- Prostaglandins
- Bradykinin
- NO
- Dopamine
- ANP
In the early proximal tubule Na+ uptake across the apical membrane is primarily coupled with which other molecules?
Which is the main one?
- HCO3- (primary)
- Glucose + AA’s
- Pi and lactate
In the late proximal tubule, Na+ reabsorption is primarily coupled with what other ion?
- Cl-
- Primarily via transcellular route
Reabsorption of Na+ in the PCT is primarily driven by what?
Na+-K+-ATPase
In the loop of Henle which part is concentrating and which part is diluting?
- Concentrating during descent, only permeable to H2O, NaCl remains in tubule
- Diluting during ascent, H2O is impermeable and NaCl is reabsorbed
Function of the principle cells and intercalated cells in the late segment of the distal tubule?
- Principal cells = Na+ reabsorption, K+ secretion, H2O reabsorption
- Intercalated cells = acid base balance
Effect of nicotine and alcohol on ADH?
- Nicotine will increase ADH
- Alcohol will decrease ADH
What 4 events/hormones inhibit renin secretion?
- Increased Na+ and Cl- reabsorption across the macula densa
- Increased AFFERENT arteriolar pressure
- ADH
- Angiotensin II via negative feedback
What are the effects of Aldosterone on Na+, K+, and H+?
- Increases Na+ reabsorption
- Increases K+ secretion
- Increases H+ secretion
