1. Renal Fraction Filtration Fraction
Fig 25.1
Fig. 25.5

2. Net Filtration Pressure (NFP)
Definition…
HPg = glomerular hydrostatic press.
“BP in glomerulus”
Avg = 55 mmHg
OPg = glomerular osmotic press.
OP of blood in glomerulus
Avg = 30 mmHg
HPc = capsular hydrostatic press.
(like “afterload”)
Avg = 15 mmHg
NFP = HPg – (OPg + HPc)
NFP = 55 – ( )
NFP = 10 mmHg
Avg = 7 – 10 mmHg
fig 25.13

3. Glomerular Filtration Rate (GFR)
Definition…
GFR is directly proportional to NFP
Avg = 125 ml/min (180 L/day)
GFR determines rate of flow thru nephron…
If too fast…
If too slow…
Changes in HPg or OPg will alter _____ and therefore _________
Flow Rate of +/- 30% normal
Clinical Applications – What if…
Hemorrhage…
Fight or Flight…
Kidney Infection w glomerulonephritis…
fig 25.13

4. Regulation of GFR is really regulation of NFP…
Intrinsic vs. Extrinsic Controls
Intrinsic Controls a.k.a. “autoregulation”
Myogenic Mechanism…
Tubuloglomerular Feedback Mechanism…
fig 25.13

5. 1. The Myogenic Mechanism (Reflex)
fig 25.13

6. 2. Tubuloglomerular Feedback Mechanism
Macula Densa cells of the JGA
“sample” filtrate at top of LOH for [NaCl]
If too much… flow rate was _______
If too little… flow rate was _______
So how should we adjust the afferent arteriole in each case?
MD cells release more ATP to vasoconstrict afferent arteriole.
-Less ATP to vasodilate.
Fig 25.8

7. Intrinsic Controls (summary)
Myogenic mechanism
Tubuloglomerular Feedback
fig 25.13
can ‘handle’ MAPs mm Hg
Maintain GFR at 125 ml/min +/- 30%
If MAP <80 mm Hg …
If MAP <50 mm Hg …
Kidney “failure”

8. Extrinsic Controls When need to “override” the intrinsics
e.g. F/F and hemorrhagic shock
Systemic BP has priority over NFP
Capable of shunting 21% BF (CO) from kidneys to other organs
E.g
F/F
Sympathetic stimulation constricts arterioles (esp. skin, digestive organs, and kidneys)
At kidney, Epi & NE specifically constricts afferent arterioles
Hemorrhagic Shock
Low BP in glomeruli initiates the renin-angiotensin mechanism. …
Angiotensinogen
Angio I
Angio II
Vasoconstriction
Aldosterone
ADH
fig 25.13

9. Good summary of Regulation of GFR
Fig 25.14

10. Regulation of ECF Concentration & Volume
Text title is “Regulation of Urine Conc & Volume” but…
Osmolality… vs. Osmolarity…
Osmolality is based on # solutes / kg of water
Osmolarity is based on # solutes / Liter of water
In human physiology the difference is <1% so…
Osmoreceptors in hypothalamus respond to osmolarity
Normal (homeostasis) = 280 – 300 mOsm
NFBMs control both input (thirst) and output (urine vol.) to achieve homeostasis
To control output we must be able to reabsorb water from filtrate via osmosis
The Countercurrent Multiplier and Exchanger make this possible

11. Osmolarity in different parts of the kidney
Not in 9th ed.
Nephrons (2 types)
Cortical 85%
JuxtaMedullary 15%
This hypertonicity is what enables us to reabsorb water from our filtrate by osmosis.
Collecting ducts of all nephrons must pass thru hypertonic medullary layer where the water may be reabsorbed.
The Countercurrent Multiplier and Exchanger topic is all about “How do we maintain a hypertonic medullary ISF?”

12. Osmolarity of blood is monitored at hypothalamus, not kidney
Influence on kidney is via ADH

13. Less ADH yields dilute urine More ADH yields conc. urine
Fig 25.17

14. Diuresis & Diuretics Fig 25.5 Diuresis = urine production
not normally adjusted by changes in NFP or GFR (autoregulation prevents this)
- but rather by adjusting reabsorption of electrolytes and water from filtrate in the DCT and Collecting tubule
Controlling urine vol. and conc. is not #1 objective
Controlling blood vol and conc (ECF) is #1 priority
Can’t change one without the other
Most adjustments made by ADH and aldosterone

15. Diuresis & Diuretics Fig 25.5
Diuretic = anything that increases diuresis
2 major categories:
1) Those that inhibit reabsorption of Na+ & Cl-
and therefore water
e.g. Caffeine, Lasix, HCTZ, others
2) Those that act as “osmotics” …
e.g. Glucose in cases of DM
e.g. Mannitol for cerebral edema
Also alcohol…

16. Renal Clearance (a.k.a. Plasma Clearance)
Overall function of kidneys is to remove or “clear” the plasma of certain substances
“renal clearance test” or “plasma clearance test”
Normally expressed in ml/min
Logic - 3 possible fates for substance in filtrate:
Reabsorbed partially or totally
Secreted partially or totally
Neither reabsorbed nor secreted
If a substance is neither secreted nor reabsorbed then its renal clearance value represents…
GFR (125 ml/min)
e.g. of above is inulin
If substance is 100% secreted its renal clearance value represents total BF through kidney…
renal fraction
e.g. of above is PAH para-aminohippuric acid
Natural indicators: creatinine and BUN
Fig 25.5

17. Tubular Max (a.k.a. Transport Max)
Fig 25.5

18. Solvent Drag
Fig 25.5
p / 971

20. Electrolyte Composition of Body Fluids
Fig 26.2

21. OP of blood is mostly due to ____________________ and these do not change rapidly
90-95% of all ECF electrolytes come from NaHCO3 and NaCl
Na+ is the only cation in ECF that exerts significant OP and its [ ] can change quickly
Therefore… Changes in OP of blood are likely due to changes in ______ rather than _____________
Predicting osmolality based on [Na+]…

22. Changes in electrolytes tend to cause “fluid shifts”
Fluid shifts (osmosis) alter [ ]s
Altered [ ]s affect thirst mechanism and kidney function

23. Electrolyte Balance
Regulation of ECF [ ] of :
Potassium
Calcium
Sodium
**For the topic of electrolyte imbalances all “hyper-” and “hypo-” refer to ECF and not ICF.

24. Potassium Ion, K+ Normal range: 3.5 – 5.5 mEq/L
The most abundant intracellular cation
But ECF [K+] strongly influences mem. potentials
Recall #1 factor influencing RMP?...
“the tendency for K+ to diffuse out of the cell…”
If Hyperkalemia…
The tendency for K+ to diffuse out is …
So the RMP is…
Nerves and muscles more responsive but only initially
Later, when RMP is no longer greater than threshold…
they become unresponsive = flaccid paralysis

25. Potassium Ion, K+ (cont’d)
If Hypokalemia…
Tendency for K+ to diffuse out is greater
So RMP is greater
Nerves & muscles become unresponsive = flaccid paralysis
Cardiac muscle is esp. sensitive to both hyper- and hypokalemia
Weak contractions and arrhythmias
“weak” with hyperkalemia b/c contractility is proportional to RMP
Brain is prone to seizures when [K+] is low

26. Regulation of [K+] At the kidneys:
Fig 25.15
At the kidneys:
90% of the K+ in filtrate is reabsorbed automatically
The remaining 10% stays in the filtrate and leaves the body.
If we need to get rid of more than 10% (and we usually do) it’s by_________
In Hyperkalemia… rate of secretion of K+ is adjusted two ways:
When ECF [K+] is high, more K+ moves into nephron tubule cells and more K+ is secreted... sort of like autoregulation
When ECF [K+] is high it  release of aldosterone which  secretion of both K+ & H+ in trade for Na+

27. Regulation of [K+] If hypokalemic… Logical solution? ________________
Fig 25.15
If hypokalemic…
Logical solution? ________________
(reabsorb more)
But only very minute amts of K+ can be reabsorbed in the collecting tubule.
you will still lose 10% K+ in urine.
Kidneys cannot compensate.
Only remedy is to  dietary intake

28. Calcium Ion, Ca++ Normal range (adults): 9-10ish mg/dl
ECF [Ca++] affects both neurons and muscle cells via its effects on RMP
Role at cell surface?…
Keeps the VG Na+ channels closed
So HyperCalcemia would make them…
Hyperpolarized and less responsive
And HypoCalcemia would make them…
Depolarized closer to threshold and more responsive
Heart muscle is esp. sensitive to both hyper- & hypocalcemia
Weak contractility
Arrhythmias
Cardiac arrest

29. Regulation of ECF [Ca++]
Bones = reservoirs of calcium phosphate – 99%
Only 1% circulates in ECF
98% of the Ca++ in filtrate is reabsorbed

30. Regulation of ECF [Ca++]
Fig 25.15
Bones = reservoirs of calcium phosphate – 99%
Only 1% circulates in ECF
98% of the Ca++ in filtrate is reabsorbed

31. Regulation of ECF [Ca++]
Fig 16.13
Almost totally by…
PTH
3 target tissues of PTH…
Kidneys
Bones
Sm. Intestine
Calcitonin could lower [Ca++] but …

32. Sodium Ion, Na+
Normal range: mEq/l
The #1 most abundant cation in ECF
The #1 most influential cation on OP of blood
(but plasma proteins are still #1 overall)
Is responsible for most s in OP of blood
Water follows Na+ so any s in [Na+]…
Therefore also s vol. and conc. of …

33. 90% of Na+ in filtrate is reabsorbed in PCT & LOH
Sodium Ion, Na+
Fig 25.15
At Kidneys
90% of Na+ in filtrate is reabsorbed in PCT & LOH
Most of the remaining 10% is reabsorbed in DCT and Collecting T.
1) Controlled mostly by [aldosterone]…
A) Aldosterone is released mostly in response to the renin-angiotensin mechanism in response to…
 BP
 [NaCl] in filtrate
Sympathetic stimulation
B) Aldosterone also released by direct stim. of adrenal cortex by  [K+]
2) also controlled by ANP when BP is high.
ANP inhibits reabsorption of Na+ at the collecting ducts
Estrogen mimics aldosterone…

34. Release & effect of aldosterone
Fig 26.8
& H+ secretion as well

35. Sodium and Water Balance
Fig 26.10

36. Release of ANP
Fig 26.9

37. What if…
You consume a high sodium meal?...
You lose 5-10% of blood volume by hemorrhage?...

38. Clinical Applications: IV Solutions…
Recall isotonic, hypertonic, hypotonic?
Most IV solutions are _______________
e.g. 0.9% Normal Saline, D5W, & Lactated Ringers
A few are hypotonic… e.g. 0.45% normal saline
A few are hypertonic… e.g. Mannitol

39. Fig 26.2
** Note: ICF Ca++ does not include what’s inside SR **

40. Recall…
Normal range of pH of blood? _______________
Extreme low & high? _______________
If less than 7.35? ____________
If greater than 7.45? ____________

41. ACIDOSIS pH < 7.35 Due to too much H+ or too little HCO3-
Major effect = depression of CNS
S&S (generalized)
Headache & lethargy
Reduced LOC and possibly coma
RR and depth (if breathing is compensatory)
(but hypoventilation can be the cause)
Reduced BP due to:
systemic vasodilation (circulatory shock)
Weak and irregular heart beat

42. Due to too little H+ or too much HCO3-
ALKALOSIS
pH > 7.45
Due to too little H+ or too much HCO3-
Major effect = hyperexcitability of the entire NS
Peripheral nerves affected 1st, CNS later
S&S (generalized)
Numbness & tingling in fingers & lips
Pt appears nervous, jittery, “high strung”
Spasms & tetany of hands & forearms
RR and depth (if breathing is compensatory)
(but hyperventilation can be the cause)
If severe enuf… 1) convulsions
2) death due to tetany of respiratory muscles

43. Alkalosis cont’d
The explanation…
Alkalosis causes plasma proteins to change shape & bind up ECF Ca++ that should have remained ‘free’… thus hypocalcemia
So RMPs …

44. “Respiratory” or “Metabolic” identifies the cause…
In order of frequency…
Respiratory Acidosis
Metabolic Acidosis
Respiratory Alkalosis
Metabolic Alkalosis

45. Causes of Acidosis & Alkalosis
Hyperventilation due to emotions
Resp. alkalosis
Reason:
Excessive vomiting of stomach contents
Met. Alkalosis
Excessive ingestion of sodium bicarb antacids

46. Aspirin overdose (acetylsalicylic acid) Met
Aspirin overdose (acetylsalicylic acid) Met. Acidosis Reason: COPD, late stages Resp. acidosis Uncontrolled diabetes mellitus Partial heart failure: CO and tissue perfusion is reduced Met. acidosis (a.k.a. lactic acidosis)

47. Alcohol or narcotics overdose
Resp. acidosis and/or Met. Acidosis
Reason:
Diuretics that deplete K+ (also H+)
Met. Alkalosis
Severe diarrhea
Met. Acidosis
More examples p / 1016 – OYO All are fair game.

48. The ABCs of ABGs pH
Uncompensated Normal or Uncompensated
Acidosis Compensated Compensated Alkalosis
Acidosis if… Alkalosis if…
Pco
HCO

49. Interpretation of ABGs
pH Pco2 HCO3-
uncomp. met. alkalosis
uncomp. resp. acidosis
comp. met. acidosis
uncomp. resp. alkalosis
uncomp. met. acidosis
normal

50. 7.36 55 34 comp. resp. acidosis 7.30 51 32 uncomp. resp. acidosis
OYO
comp. resp. acidosis
uncomp. resp. acidosis
comp. resp. alkalosis

51. OTT - Water intake vs. water output
Fig 26.4

52. OTT - The thirst mechanism
Fig 26.5

53. OTT

54. OTT - Distribution of Electrolytes
Fig 26.2

55. OTT – Both Labs on pH & Acid–Base Balance
pH values for blood
pH values for urine
Buffer Systems
Respiratory Adj.
Renal Adj.

56. OTT - Regulation of K+, Ca++, Na+
Fig 25.15

57. OTT - NFP & GFR

58. OTT - Regulation of GFR (and NFP) – via the JGA

59. Less ADH yields dilute urine More ADH yields conc. urine
Fig 25.17