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The Role of the kidneys is to Maintain balance between ______ _____& _____ ______ all the while keeping _______ levels w/in limits tolerable for life, with enough reserve capacity to deal with ________ _______.
The Role of the kidneys is to Maintain balance between _FLUID INTAKE_& _FLUID LOSS_ all the while keeping _ELECTROLYTE_ levels w/in limits tolerable for life, with enough reserve capacity to deal with _EXTREME SITUATIONS_. ( to help regulate body fluids)
Fluid intake & outtake are balanced what are the intakes each day normally? (Fluid/ Water Gain)
Fluid Gain:
1. Food & Drink =2.2 L/Day
2.Metabolism (glucose + O2=> CO2 + H2O +ATP) = .3L/Day
SO
2.2L (food/drink) + 0.3L (metabolism) = 2.5L/day intake
Fluid intake & outtake are balanced what are the outakes each day normally? (Fluid/ Water Loss)
Fluid Loss:
1.Urine = 1.5 L/day by kidneys
2.Insensible Water Loss by Skin (sweat, etc) & Lungs (breathing, talking) = 0.9L/day
4. Feces= 0.1L/day
SO
Output=
1.5l (Urine) + 0.9L (Insensible Water Loss) + 0.1L (Feces)= 2.5 L
The Body has 3ish compartments wehere water is containedwhere is the most and least?
ICF
ECF
-plasma & interstiail
1.Intracellular FLuid= 40% BW (most)
2. Extracellular Fluid=20% BW
a. Interstiial Fluid= 11L
b. Plasma 3L ( 7-8%bw)
What is the Total body water volume and waht % of body weight is the ideal 70kg male?
42L
~60% of body weight
Do males or females contain more water? what is the % for women ideally?
Females contain less water bc increased subcutanous fluid,.
~50% BW for women
As we age what happens to our water content?
Average older male and female?
Kids water content?
As we age we dry up= Decrease water content
Males= 50% BW
Female= 45% BW
Kids= 70% BW
ICF is ~= ____ of TBW
ECF is ~= _____ of TBW
Interstiual Fluid (ISF) ~= ____ of ECF
Vascular Fluid (VF) ~= _____ of ECF (Plasma + RBCS)
ICF is ~= _2/3_ of TBW
ECF is ~= _1/3_ of TBW
Interstiual Fluid (ISF) ~= _2/3_ of ECF
Vascular Fluid (VF) ~= _1/3_ of ECF (Plasma + RBCS)
Distribution of body fluid across cell membranes from ISF=>ICF is determined by what type of forces? why? Mainly from ??
Osmotic Foces- Mainly from Electrolytes
( bc H2O moves quickly through membranes, but solutes won't.)
Distribution of Body Fluids across Capillaries from Plasma=>ISF is determined by what forces? (2)
Determined by both:
Hydrostatic & Colloid Osmotic (Oncotic) forces (depends on starling forces/equilibrium)
=Due to lg particle molecules- proteins in capillaries resists fluid of movement out & promote fluid in.
(Usually plasma=> ISF=>ICF)
What are the Cation and Anion that compose 90% of the total ECF osmolarity?
Cation= Na+
Anion= Cl-
What is 50 % of the ICF osmolarity?
K+ ( Cation)
What is the cell membrane permeable and impremeable to?
Cell membrane:
High permeability to H2O ( only if Change in osmolarities from 1 compartment to another.
=> Relative impermeability to small solutes ( Na, Cl & other electrolytes)
Fluid Distribution between ICF & ECF is determined mainly by the ????
OSMOTIC EFFECT of these SOLUTES (Na+, CL-, & other electrolytes) ACTING Across Cell Membrane
THe difffusion of water across a selectivevely permeable membrane from a region of high H20 to one that has a lower H2O Concentration is known as?
Osmosis
Osmotic Pressure is?
The amount of pressure required to prevent osmosis!
If there is a change in NaCl content in the ECF, makint it a hypertonic, then what has to happen to try to maintain balance?
Water has to move from ICF to ECF. Bc NaCl can NOT move from ECF to ICF compartment bc as many solutes are, they are inpermeant to cell membranes.
What effect does Hydrostatic pressure differences have on fluid movement across cell membrane?
Hydrostatic pressure differernces have only a small effect on fluid movement across cell membrane.
Intracellular solution - Most osmotic pressure from?
K+ ( K+ highly concentrated in cells bc of the Na/K ATPase pump
1. Extracellular solution - Most osmotic pressure from?
2. Plasma vs. ISF differernces is due to?
1. Most osmotic pressure in EC solution from Na+ ( due to Na+, albumin (most abundant protein in plasma))
2.Plasma vs. ISFdiffercences (about 20mmHg) due to PROTEINS in PLASMA
Osmotic Pressure (O.P.) between 2 solutions (EC & IC) separated by semi-perm membrane= _____
TONICITY
_____tonic = greater osmotic difference . One is high the other is low
HYPERTONIC
Hydrostaic & Colloidal Osmotic Starling's (oncontic) pressure between what? Regulation of fluid exchange
Plasma and Interstitial Fluid
Osmotic pressure is btween what as regulation of fluid exchange?
ICF & ECF compartments
Conc. osmotically active particles in soln. expressed as osmoles/L is ???
OSMOLARITY
Conc. osmotically active particles of solute/kg of solvent is ???
OSMOLALITY
Same conc as ECF (300 mOsm/L) is?
Isosmotic
Soln in which cell vol,. stays the same and there is no water movement is known as?
Isotonic
If a cell is >300mOsm/L the cell has what tonicity?
Hypertonic= Cell Shrinks
If a cell is <300mOsm/L the cell has what tonicity?
HYPOTONIC Cell Swells
Intracellular Solute concentration for nromal should be between what mOsm/L?
~282-300 mOSmL
Tonicity of fluids depends on the?
Concentration of cell impermeant solutes
Tonicity:
1. Isotonic-
2. Hypotonic-
3.Hyertonic-
1. Isotonic-Equal osmolarity w/ECF
2. Hypotonic- lower osmolarity than ECF <300
3.Hyertonic- Higher osmolarity than ECF >300
What must be kept between ICF & ECF and how quickly is it attained?
Osmotic Equilibrium must be kept between ICF & ECF,
Osmotic Equilibrium between ICF & ECF is attained Rapidly W/in Mins.
Osmole refers to the?
Ex:
How many osmoles are in the following:
1M Glucose=>
1M NaCl=>
1M Na2SO4=>
Osmole= Refers tothe # of Osmotically Active Particles in a Solution rather than to the Molar Concentration.
1M Glucose=> 1 osm/L
1M NaCl=> 2 osm/L
1M Na2SO4=> 3 osm/L
If the solution isn't isotonic... THE ONLY REASON FOR FLUID TO MOVE IS ????
OSMOLARITY DIFFERENCE from 1 chanmber to another
IF put a cell in hypotonic solution what 2 things happen?
1. Cell Expansion (Swells)
2. Extracellular volume Increases
Due to water moving into the cell
(soln <300)
IF put cell in Hypertonic solution what happens?
Cell Shrinks bc water moves out of the cell.
Soln is >300
What is osmolality detemined by?

(Check out slide 17- ppt 1)
Total concentration of allthe solutes present.
1.What is the Solution's Tonicity determined by?
2. Tonicity involoves?

(Check out slide 17- ppt 1)
1. Tonicity is determined by:The concentration of only those solutes that Do NOT "PEnetrate" the cell.
2. Tonicity involves:
a. Solute Concentration
b. Cellmembrane (Permeability)
c. Cell Volume
How will skeletal m. cells immersed in a solution containing 150 mOsm of NaCl & 300 mOsm of glycerol per L react?
450mOsm= Hypertonic so cell shrinks, but bc glycerol can penetrate the cell membrane (unlike NaCl) the cell will shrink intially but then return to normal volume. The same would happen if the concentration was with Urea or other permeable solute.
What would you expect if a normal person loses 2L of sweat & simultaneously drinks 2L of pure water?
A. An Increase in EC Osmolarity
B.An Increase in EC Vol.
C. An Increase in IC Osmolarity
D. An Increase in Incracellular Vol.
E.AN Increase in Plasama Sodium Concentration
D. An Increase in Intracellular Volume. This is bc there 2/3 of water goes here if drink pure water... Look at slide 20 ppt 1 for more info of why others are wrong
What are the changes in the following variables agfter giving 2L of 0.9%NaCl i.v.?
A. ECF Vol. =>
B.ECF Osm. =>
C.ICF Osm.=>
D.ICF Vol.=>
0.9% NaCl is Isosmotic
A. ECF Vol. => Increase (bc can't move from ECF to ICF)
B.ECF Osm. => No change bc isotonic
C.ICF Osm.=> No Change-bc doesn't move into ICF
D.ICF Vol.=>No Change
What are the changes in the following variable after giving 2L of Water i.v.?
A. ECF Vol. =>
B.ECF Osm. =>
C.ICF Osm.=>
D.ICF Vol.=>
Water is Hypo-Osmotic
A. ECF Vol. => Increase (1/3 water goes here)
B.ECF Osm. => Decreases (diffuses/dilutes out)
C.ICF Osm.=>Decreases ( bc 2/3 of water comes here so increase in vol.)
D.ICF Vol.=> Increase (bc 2/3 of water goes here)
What are the changes in the folllowing variables after giving 2L of 3% NaCl i.v.?
A. ECF Vol. =>
B.ECF Osm. =>
C.ICF Osm.=>
D.ICF Vol.=>
3% NaCl is Hyperosmotic
A. ECF Vol. => INcreases (bc can't move from ECF to ICF)
B.ECF Osm. => Increases
C.ICF Osm.=> Increases ( bc move fluid from IC to EC bc need more there)
D.ICF Vol.=> Decreases (Bc move water to ECF)
Clinical fluid issues is offem associtated with what?
Blood Na+ levels isnce Na+ major determinate of plasma
What is the condition that water is loss or excesss NA+?
This stimulates thirst so usually not that big of a problem.
Hypernatremia
What condition is caused by excess water or loss of Na+ ?
Can cause movement of water out of plama into cells causing intracellular edema
Hyponateremia
Ecess fluid in body tissues.
-movement of fluid into tisues IC or EC tissue?
Edema
What is the most common electrolyte disorder?
Hyponatremia
Hyponatremia = Decreased plasma sodium concentrraion bc of 2 things?
1. Loss of NaCl from ECF (Dehydration) = decrease of aldosterone
a. diarrhea & vomiting
b. Overuse diuretics
c. Addison's ds
2. Addition of Ecess water to the ECF (excess water retention)-Overhydration
a.Excess ADH= cause fluid to move into cells= cause swelling
Acute Hyponatremia is caused by loss of Na+ or ecessH2O, there is diffusion of H2O into the cells & ______ of the _____ tissue
&Swelling of the Brain tissue
= Very Dangerous and can cause a comma or death
Acute hyponatremia caused by loss of Na+ or excess H2O, diffusion of H2O into the cells & swelling of the brain tissue. THis stimulates transport of what out of the cell? Which causes water to do what?
This stimulates transport of Na+, K+, & organic solutes out of the cells, causing water diffusion OUT of the Cells.
With Chronic hyponatremisa the brain swelling is attenuated by?
the transport of solutes from the cells, brain adjusts to swelling.
Hypernatremia is assocated with increase plasma sodium concentratio nthat leads to increase in ?
Osmolarity
Primary loss of water in ECF(dehydration) in someone who has Hypernatremia is due to?
1. Inabilityto secreate ADH (diabetes inspipidus)
2. Dehydration due to sweatingduring prolonged, heavy exercise
Person with Hypernatremia has excess EC NaCl bc?
As in Ecessive secretion of Aldosterone (from zona glomeruasa of adrenal gland) Retain too much Na & h20 stimulates thrist
What 3 things cause Intracellular Edema?
1. Hyponatremia
2. Depression of the metabolic systems of the tissue- Na/K pump failure ( Where pump fails so there is an increase of Na inside the cell which causes water to flow into the cell to try to dilute Na= INFLAMATION)
3. Impaired Nutrition to the cells-inflammattion- eg. Burns. ( increased permeability of cell w/ burn damage so more Na flow into cell and water follows so cell swells
Extracellular Edema is caused by Increased ISF Vol. or VF volume ?
caused by what 2 things?
Increased ISF Vol (Swelling)
-Caused by:
1. increased capillary filtration
2. Failure of lymphatics to return interstitial fluid to circulation
Conditions that cause Edema:
1. ____ (high, low) Capillary Hydrostatic Pressure
2.____ (increased, decreased) Plasma Proteins (___ (high/low) Oncotic Pressure)
3._____ (increased, decreased) Capillary Permeability
4.Blocakge of _______
1. _HIGH_ Capillary Hydrostatic Pressure
2._DECREASED_ Plasma Proteins (_LOW_ Oncotic Pressure)
3._INCREASED_ Capillary Permeability
4.Blocakge of _LYMPHATICS_ (LONG FLIGHT SWOLLEN ANKLES- unable to return lym to circulation= LYMPHAEDEMA
Determinants of Capillary Filtration:
1. Capillary Pressure- Aids in what?
HIgher the cap Pressure=
2.Higher the Oncotic pressure=
3. If in protein losing ds=> lots of fluid ?
1. Capillary Pressure- Aids in moving stuff out
HIgher the cap Pressure= MOre stuff moved out
2.Higher the Oncotic= Ressits movment out.
=> Produced by proteins
3. If in protein losing ds=> lots of fluid ? Lost of fluid out promotes fluid into cap.
Lympatic failure = Edema when?
ISF can't flow through the lympatics to the Plasma
What is a metabolism ds caused by lack of blood flow, hyponatremima, NA/K pump failure =>water follows Na+ so get cell firing & potential rupteruring inflammation can make cells leaky to Na+ and other ions?
Intracellular Edema
What is characterized by ecessive cappillary filitarion= increase cap permeapibility pittying edema . and Insufficient lympatic drainage due to increase ISFOnconic presssure causing lymp blockage.
Extracellular edema
What is the most common cause of Edema?
HEART FAILURE
=> Low C.O. and INcrease venous move through.
HEart failure causing Edema is characterized by?

see slide 34- ppt1
1. Increased capillary filtration
2.Decreased salt & water excretion by kidneys (compensation for (low systolic) BP) -leads to increased Blood vol. which increases capillary pressure = (+) feedback.
Where are fluids & solutes filtered and urine begins to form?
After the renal A,V & urter enter kindey at hilius, vesselse progressively branch into 1.Interlobar, 2.Arcuate, 3. Interlobular (=raida) arteries. Then Into AFFARENT ARTERIOLIES supplyu Glomerus capsule of Glomeral Tuft... this is where fluids& suolutes are filtered & urine formation begins
Glomerus caps coalesce , exit glomerus not as venules but as ________ ________. Lead to _____ Capillary network, _______ capillaries, surround ___ _____.
Glomerus caps coalesce , exit glomerus not as venules but as _EFFERENT ARTEROLIES_Lead to _2ND_Capillary network, _PERITUBULAR_ capillaries, surround _RENAL TUBULES_.
What is the functional unit of the Kidney, where is it located and how many are there?
Nephrons- 1million on outside cortex =2million all together.
-Decrease as we age
Nephrons filtrate blood from what to where?
Filtration of blood from AFFERENT Arterol to bowmans capsule
Why are most vessel branchs in the cortex of the kidney?
Bc thats wehre the nephorons are
What are th7 functions of the Kidney other than formation of urin?
1. Excretion of Metabolic waste products
2. Excretion of Foreign chemicals
3. Secretion, Metabolism, & Excretion of hormones: a. Renal erythopoetic factor, b. 1,24 dihydroxycholecalciferol (vit d3), c. renin
4.Regulation of Acid-base balance ( acidosis= kid response by ^H+; alkadosis- kidney response by ^HCO3-)
5.Gluconeogenesis (prolongfasting situations)
6. Control of Arterial Pressure (blood vol.)
7. Regulation of Water & electrolyte excretion.
Glomerulus is responsible for?
The more folds in glomerulus=
Filtration of our blood
The more folds in glomerulus= greater filtration more things can be filtered
Renal tubule and Peritubular capillaries are responsible for?
Reabsorption and secrtion ( depending on what is needed)
Glomerulus & Renal Tubules/Peritubular capillaries work together:
Excretion=
Excretion= Filtration- Reabsorption + Secretion
Thick ascending limb is important bc?
It contrarates and dilutues urine
Cortical Nephrons are located where and have what LoH?
-Located in outer cortex
- Have short LoH, Penetrate only short distance into Medulla
-(7/8 of nephrons are here)
Juxtamedullary Neprons located? have what LoH? What surronds them? Why are the sixes of LoH important?
- Located in deep Cortex adjacent to medulla
-Have LONG LoH , extend way down into Medulla = important for diluting/ concentrating our urine)
-Surrounded by EFFERENT Arterioles, branch into PERITUBULAR Capillaries called,VASA RECTA
Peritubular capillaries= ___ capillaries
- For fx?
- extend into Vasa recta=
Surond what?
Peritbular Capillaries= 2nd caps
- For Reabsorption or Secretion
- Extend into Vasa Recta ( long straight vessels)
- Surround LONG LoH allowing them to reabsorb or secreate contents
How much of the C.O. is Renal Blood flow?
Approx. 1.1 L/min or 25% of C.O.
Renal Circulation is unique in that it has 2 capillary beds in series which are>
1.Glomerous, in glomerular Tuft
2. Peritubular capillaries surrounds colleting tubules
High hydrostatic presssure has what effect on GFR and resorption?
-Increases GFR ( filtration from glomerular caps)
-Decreases Resorption from Peritubular Capillaries
Low Hydrostatic Pressure has what effect on GFR and Resorption from pertibular capilalaries?
-Decreased GFR
-Increased Resorption from Peritubular Capillaries
What is somewhat variable, not selective ( except for proteins) averages 20% of renal flow, as renal blood enters into glomeruls only 20% is actively filtered the rest recirculates... this is ?
a. Filtration
b. Reabsorption
c.Secretion
d. Excretion
A. Filtration
Reabsorption is highly Variable & Selective, most electrolytes ( Na (60% intially but evenally all), K, Cl) & nutritional substances (glucose) are almost _______reabsorbed.
- Most Waste products ( urea) are _____ Reabsorbed
Reabsorption is highly Variable & Selective, most electrolytes ( Na (60% intially but evenally all), K, Cl) & nutritional substances (glucose) are almost _COMPLETELY_reabsorbed.
- Most Waste products ( urea) are _POORLY_ reabsorbed.
What is variable; important for rapidly excreting some waste products (H+), foreign substances (including drugs), & toxins.
a. Filtration
b. Reabsorption
c.Secretion
d. Excretion
C. SECRETION
Describe the Renal Handling of the following substances as in if they are filtered, reabsorbed, secreted or a mixuture?
A. Inulin(plant iv only)=
B. Creatine (skeleteal m.)=
C. Glucose/ AA
D. Na+=
E.PAH=
A. Inulin(plant iv only)= COMPLETELY FILTERED (good measurement of GFR)
B. Creatine (skeleteal m.)= 90%Filtereted, small part secreted, but still great for GFR measurement bc made in body)
C. Glucose/ AA=Filtrated & COMPLETELY REabsorbed
D. Na+=Filtrated - partially reabsorbed,but time gets to urin almost allreabsorbed
E.PAH=Filtrated then Most is SECRETED (clearance of this can be used to measure RPF)
1. GFR =
2. Plasama Vol. is filtered =~
3. Filtration Fraction=
1. GFR= ~125ml/min = 180L/day
2. Plasma vol is filtered=~60 times/day
3. Filtration Fraction= (GFR/RPF)= ~0.2 = only about 20% of plasma is filtered- bc protein in urine is bad.
What are the 3 major determinates of the ability of a solute to Penetrate the Glomerular Membrane?
1. Molecular Size= (Sm. molecules filter better than lg ones)
2.Ionic Charge ( cations (+) filter better than anions (-) )
3. Proteins are both Lg & negatively charged, hence do NOT FIlter Welll.
(if Protein in urine= bad bc that means glomerus problems)
If there is a more(+) electrical charge of the solutes=> what does this mean for passage through the filtration membrane?
More (+) charge=> Higher Filterability
In minimal change nephropathy- loss of (-) charge on Glomulus BM results in?
1. Proteins filtered through GBM
2. Proteinuria= loss of (-) charge=> protein loss into urine
The reason for differences in filterability btwn substances and charges is that the (-)Charges of the BM & Podocytes provides an important means for ???
Restricting Large (-) charged molecules, Including plasma proteins
The 7 Functions of GFB??
1. Prevents passage of rbcs, wbcs, platelets , & proteins
2. Has Thick glycocalyx surrounding podocytes has strong (-) charge due t heparn sulfate
3. Fx as Size & Charge Filter
4.Selectively limits molecules that pass through:
-Lg & (-) charged molecules retained in Plasma
-Small, (+) charged molecules eaisly filtered.
5.Loss of (-)charge=>protein loss into urine)= PROTEINURIA
6. Permits passage of Water & ions
7. Forms an Ultrafiltrate of blood
What happens if you lose the (-) charge on BM?
Lose ability to discrimanate & (-) charge proteins get through-= this is bad
Net Filtration Pressure =?
Net Filtration Pressure(NFP)= Glomerular Hydrostatic pressure- Bowman's capsule pressure- Glomerular Oncotic Pressure
GFR =
GFR= Kf x NFP
Normal GGR= 125ml/min
Kf= 12.5ml/min/mmHg
Why does NFP Decrease along the Glomerulus?
Bc of INCREASING Oncotic Pressure.
-(NFP is greater at the beginnigng when blood 1st goes into glomerulus than at the end bc more as more is filtureed it leaves the glomeruls and proteins are left inside.)
- Filtration pressure falls as blood moves through glomerulas
What is Glomerular capillary filtration coefficient really? Kf?
Kf= hydraulic conductivity x surface area
-=> Normally not highly variable
What are 3 Diseases that can REduce Kf & GFR? (decrease filtration)
1. Chronic hypertension
2. Obesity/ Diabetes Mellitus
3. Glomerulonephritis
Bowman's Capsulse Hydrostatic Pressure (Pb)- Normally changes as a fx of what? is it a regulator of GFR?
-Normally Changes as a FX of GFR, NOT a Physiological regulator of GFR
In Bowman's Capsule Hydrostatic Pressure (Pb) What are the 2 obstructions possible and what causes each?
1. Tubular Obstruction
a. Kidney sotones
b. Tubular necrosis
2. Urinary Tract Obstruction
a.Prostate hypertrophy/cancer
What is the 1' determinant of GFR?
Glomerular Hydrostatic Pressure (Pg) = determinant of GFR most subject to physiological control.
What factors influence Glomerular Hydrostatic pressure (Pg)?3
1.Arterial Pressure ( effect is buffered by autoregulation - dilute/concentrate)
2. AFFERENT Arteriolar Resistance
3. EFFERENT Arterilar Resistance
What 3 things Control RBF and fx to keep GFR at a faily constant level despite changes in arteial BP autoregulations:
1. Renal Autoregulation (Intrinsic)
2.Neural Controls through SNS
3. Hormonal Controls through Renin-Angiotensis system (aldosterone)
In what RBF regulation is GFR maintained despite changes in local BP & blood flow by changing diameters of arterioles & glomerular capillaries (MYOGENIC MECHANISM)
AUTOREGULATION (INTRINSIC)
In Autoregulation (Intrinsic) control of RBF- Reduced BF or Glomerular BF triggers?
1. Dilation of AFFERENT Arteriole (allow moreblood into glomerus),
2. Dilation of Glomerular Capillaries
3. Constriction of EFFERENT Arterioles (increase GFR at least temporairly)
As part of Autoregulation (Intrinsic) of RBF control:
A rise in Renal BP causes??
1. Smooth Muscle cells to Contract
2. Constricts Afferent Arterioles
3. Decreases Glomerular BF
(too much pressure = Decreases GFR)
An Increase in Renal Afferent Arteriole does what to ?
Decreases GFR + Decreases RBF
An Increase in Renal Efferent Arteriole does what?
Increases GFR + Decreases RBF
( Causess more build up of protein if really constricts it & eventuallly Decreases GFR)
Autoregulation of RBF uses 2parts of Tubuloglomerular Feedback which are? accomplished by what?
1. Contains Afferent Arteriole
2. Contains Efferent Arteriole
Accomplished via? JUxtaglomerular Apparatus (JGA)
Tubuloglomerular FB of Autoregulation accom via JGA consists of a thickened region of specialized epithelial cells lining junction of thick ascending limb of LOh & Distal Convoluted Tubule is known as? located were?
Macula Densa
- Located at base of Glomerular Tuft, contacts wall of both AFF & EFF Arterioles.
The macula densa contains Chemoreceptors that?
Detect Na in Filtrate
Juxtaglomerular cells surround what walls and secrete what?

SLIDE 32- Ppt 2
Juxtaglomerular cells- Surround wall of AFFERANT Arteriole and secrete renin
Afferent arteriole contians what kind of receptors that detect what?
BARORECEPTROS that detect changes in BP
Tubuloglomerular Feedback = Decrease in GFR stimulates??
Decrease Distal Nacl Delivery => Decrease Macula Densa NaCl Reabsorption (macula densa feedback) => Decrease Afferent Arteriolar REsistance (causes relaxtion & increase bf) => INcrease GFR (to return toward normal) this sends a (-) feedback to the decreased distal NaCl Deliivery
Normal flow of fluid through the Kidney??
1. Glomerual filtrate flows from caps into
B's capsule=> into prox con tub=> LoH (has desc & asc limps)- Desc limb Thin=> asc Limb has thin seg & thick ac limb leads into dist con tub=> collecting tubules=> collecting ducts (from rays in medulla) and eventually enter renal pelvis at renal papilla
Neural SNS Contrl of GFR directly stimulate what to release what?
Directly stimulat macula densa to release Renin
SNS Control of GFR:
SNS Stimulation causes ______ of Afferent arterioles & _____ ______ _______
SNS Stimulation causes _VASOCONSTRICTION_ of Afferent arterioles & _SLOWS FILTRATE PRODUCTION_
SNS Control of GFR:
Decreased GFR Indirectly stimulates what to do what?
MACULA DENSA Cells to INCREASE Renin Release
SNS Control of GFR:
SNS Directly stimulates JG cells to release what via what?
To release Renin Via Binding to BEta Receptors in Granular Cells
SNS Control of GFR:
During extreme stress, autoregulatory mech may be overcome in order to shunt blood to ?
Vital areas like brain, skeletal m.,& Heart, at expense of kidneys
Renin ANgiotensisn Mechanism of control of GFR by hormonal control:
JG cells release renin which stimulates A1 and converted to A2 by ACE, A2 powerful Vasoconstrictor increase BP directly and indirectly via stimulating Alsosterone release which increases Na & water resorption, INcreasesing BV & arterial BP.
WHAT ELSE does A2 doe to renal situations>?
Constricts EFFERENT Arterioles (more receptors) to Increase the Glomerular Hydrostatic pressure & Increase GFR
A Decreased GFR can be caused in a Increase or decrease of each of the following:
1. Kf ( glomerular filtration coefficient)
2.Pb (Bowman's Capsule hydrostatic pressure)
3. (pi)G (glomerular Capillary Colloid osmotic pressure)
4. Pg (glomerular Capillary Hydrostatic Pressure)
1. Kf Decrease in this= Decrease GFR
2.Pb INcrease in this= Decrease GFR
3. (pi)G = Increase in this= Decrease GFR
4. Pg = Decrease in this= Decrease GFR
The following cause a decrease in Pg (glomerular Capillary Hydrostatic pressure) and therefore a decrease in GFR?
1. ___ Ap (systemic arterial pressure)
2.____ Re (Efferent arteriolar resistance)
3. ___ Ra ( afferent arteriolar resistance)
=>Decrease Pg -> Decrease GFR
1. _DECREASE_ Ap
2._DECREASE_ Re
3. _INCREASE_ Ra
Pathophysiological problems that cause what physical determinant to decrease GFR:
1. Renal Ds, Diabetes mellitus, hypertension
2. Urniary tract Obstruction
3. Decreased RBF, Increased Plasma proteins
1. Renal Ds, Diabetes mellitus, hypertension= DECREASED KF
2. Urinary tract Obstruction= iNCREASED Pb ( prostheitc hypertrophy or renal stones)
3. Decreased RBF, Increased Plasma proteins = INCREASED (PI) G
Pathophysiological problems that cause what physical determinant to decrease IN Pg Which leads to decrease in GFR:
1. Increase sympatetitc activity, Vasoconsrtictor hormones=
2. Decrease Arterial pressure (small effect due to autoregulation)=
3. decreased A2 (ACE inhibitors)=
1. Increase sympatetitc activity, Vasoconsrtictor hormones= INCREASED Ra
2. Decrease Arterial pressure (small effect due to autoregulation)=DECREASED Ap
3. decreased A2 (ACE inhibitors)= DECREASED Re
What describes the rate at which substances are removed (cleared) fro mthe plasma?
CLEARANCE -= "Virtual Volume"
THe ____ _____ of a substance is the Vol. of Plasma completely Cleared of Substance/min by kidneys.
RENAL CLEARANCE
To Determine clearance we use what formula and assume what?
Formula= Cs= (Us xV) / (Ps)
Cs= Clearance of substance S
Us= Urine Conc. of Substance S
Ps= Plasma conc. of substance S
V= Urine Flow Rate
Assume: Whatever is missing from the plasma must be in the urine
When is Renal Clearance = to GFR?
When a substance is FREELY Filtered,but NOT REabsorbed or Secreted!
Ex- inulin
What do we use Clearance to estimate?? and what is the substance we need to do it?
Clearance to Estimate Renal Plasma Flow (RPF)
= Freely filtered and secreted by RENAL TUBULES must be COMPLTETELY REmoved from Plasma= we need PAH.
Total RPF=
PAH Clearance / PAH Extraction Ratio
We acutually use PAH Clearance to Estimate what? why?
Effective Renal plasma Flow (ERPF)
= Bc PAH is freelyfiltered and secreted and is ALMOST completely cleared from the RENAL Plasma.
ERPF= Clearance of PAH
ERPF=
ERPF= (Upah x V) / (Ppah (plasma concentration of PAH))
1.Amount enter kidney= RPF x Ppah
2. amount entered =~ Amount excreted
3. ERPF x Ppah = Upah x V (flow rate)

ERPF= (Upah x V) / (Ppah)
Clearance levels:
1. Lower than inulin or Fraction excretion (FE) < 1
or Cx< Cin indicates=
2.Higher than Inulin or FE > 1 OR Cx > Cin indicates=
1. Lower than inulin or Fraction excretion (FE) < 1 = REABSORPTION
or Cx< Cin indicates= Reabsorbtion of x
2.Higher than Inulin or FE > 1= SECRETION into tubules
OR Cx > Cin indicates= Secretion of x
what is :
-an end product of muscle metabolism
- Exported into blood contibuously by skeletal m.
-freely filtered & not reabsorbed, a small amount is secreted by proximal tubule (10%)
- Most common method for routine assessment of Pt GFR, and clearance overestimates GFR by 10%, but considered acceptible?
CREATINE
Small Changes in Pcr (plasma conc. of creatinine) indicated what in GFR?
BIGGEST CHANGES IN GFR... monitor a pt Pcr over time.
A rising plasma creatinine indicates what?
that there may be a renal problem.
- 62ml/min
( be careful to do this over time bc it will be diff for each person in considering their age, m mass and original creatine levels.
To avoid any problems with mis dx a renal problem/failure creatine clearance formual=
Creatinine clearnace=
[(140-age) x lean body weight kg] / (plasma creatine mg/dl x 72)
Tubular Reabsorption:
Transported across the tubular epithelial membranes intothe renal ISF & then through the Peritubular Cap Membrane back into the Blood is what kind of process and mech?
- Highly selective process
- Includes Passive & Active Mechanisms
Once this is reached for all nephrons, further increases in tubular load are not reabsorbed and are excreated. THIS IS A RATE.
e . glucose 375
TRANSPORT MAXIMUM
THis is the plasma concentration at which tranport max is exceeded in some nephrons. THis is determined by transport max of the whole kidney. This is CONCENTATION. Glucose apears in urine before all nephorns are thee = 200
THRESHOLD
The thing due to the fact that not all nephrons are identical and it is the curvature of a line bc some nephrons are saturated. Becasue the filtered load of glucose is normally reabsorbed, the kidney plays no role in regulating blood glucose levels
SPLAY!
If Water is reabsorbed to a greater extent than the solute, the solute will become???
MORE Concentrated in the Tubule ( ex creatine, inulin)

Secreation
IF the SOLUTe is reabsorbed to a greater exten than water, the solute will become
LESS Concentrated in the tubule ( ex glucose, aa)

REabsorbtion
Why does the Proximal Convulted Tubule (PCT) have a high capacity for reabsorption?
Bc has ciliated cells theree which enhance the overall surface area of the PCT and alllows more things to be absorbed. 65% of absorbtion occurss here.
What all is reabsorbed in the PCT?
-65% of the filtered Na, K, Cl, HCO3
-all the filtered glucose & AA ( via cotransport)
What all is secreted in the PCT?
->The metabolic waste products such as: H+ ions, Organic acids, and basesessuch as: bile salts, oxalate, urate & catecholamines
-> Harmful Drugs or Toxins
-> Para-aminohippuric acid (PAH)
What are the 3 functionally distinct segments of the loop of henle?
1. Descending Thin Segment= Thin epithelium, no brush border, few mito, low metabolic activity, very porous, Highly perm to H2O-1' H2O absorbed.- mod perm to solutes
2.Ascending Thing Segment= Ibid, almost imperable to H2O,-resorb very minor
3. Ascending Thick Segment= Thick epi cells w/high metabolic activity=>resprption of Na, Cl, K. (sm solutes)Important for concentrating & diluting urine
(Entire Ascending Limb= virtually impermable to H2O
HOw much of H2O is filtered by glom to be resorbed in LoH and where in it is most resorbed?
20% in LoH and most in Descending Thin Limb
What % of filtered Na, Cl, K (bicarb, Ca & Mg) are filtered in & resorbed in LOH where is this mostly? and what kind of transport (co, counter, etc)?
25% in LoH, mostly in Thick Ascending Limb.
=>Na co-transport results in resorp of K & CL with Na
=> Na-H counter transport mech = allows H sec into lumen w/ na resorp
Which limb of LoH is highly permeable to Water, mod perm to most solutes and Simple diffusion of substances?
Thin Descending limb
Which limb of LoH has a much lower reabsorptive capacity than the the other ascending lim and does not reabsorb significant amounts of any solutes.
- it is virtually impermeable to H2O?
Thin Ascending limb
What is the target of Loop diruetics?
Na2Cl- transporter in the thick Ascending LoH
Loop Diruetics targe Na2Cl transporter in thick ascending limb of LoH, what do loop diruteics do and name some ex?
Loop Diruetics= powerful diruetics that block the Na2Cl transporter & cause loss of Na+, K+,& Cl- in our urine by blocking this transport. Water not reabsorbed so when all these solutes are reabsorbed this Increases the osmolarity of instium & becomes more hypertonic & water remains in lumen-> important in concentrating or diluting urine.
Ex: Furosemide
Ethacrynic acid
bumetanide
Where is the the Macula dena?
in the Early distal Tubules
Characteristics of the early distal tubule . what is it functionally similar to, permeanle to /
- Fx similar to Thick Ascending Loop
-NOT Permeable to H2O= "DILUTING SEGMENT"
-Active REabsorption of Na, Cl, K, Mg
Early distal Tubules:
1. 1st portion forms:
2. Next part is:
A. Resporbs most of the:
B. H2O permeability?
1. 1st portion forms: Macula Densa (highly sensitive to NaCl levels)
2. Next part is: Highly Convoluted
A. Resorbs most of the: IONS Including Na, Cl, Ca, Mg
B. Virtually Impermeable to Water & Urea (DILUTING SEGMENT)
NaCl reabsorption in the Early Distal Tubule:
How much of filterd load of NaCl is reabsorbed here? by what transpot where?
=>~5% of filtered load of NaCl:
=>Na+_Cl- co-transporter moves NaCl from the Tubular Lumen.
=> Na_K_ATPase Pump transports Na out of the cell->interstium
=>Cl- diffuses into the intersitium through Cl- channels in basolateral membrane
What do Thiazide diuretics target? What do they do?
=>Thiazide diuretics target: Early Distal Tubules.
=>Thiazide diuretics- block/ inhibit the Na+_Cl- Co-Transporter; therefore thiazide diuretics cause the loss of Na & Cl in the urine. K+ is secreated out, so likely to have hypokalemia if on thiazide diuretics.
Both Loop diuretics & Thiazide diuretics promote ___Secretion => __________ which is
K+ Secrtion=> HYPOKALEMIA = loss of K+
In the Late Distal tubules & early Collecting ducts... What is H2O permeability dependent on? and is it permeable to urea here?
=> Permeability of H2O isdepends on ADH. (If it is available or not. If don't produce ADH, then not much H2O will be reabsorbed, but if produce a lot of ADH, then water will begin to be reabsorbed)
=> Not very permeable to Urea
What 2 important cells are the Late Distal Tubules and Early Collecting Ducts composed of?
1. Principle Cells
2. Intercalated Cells
Late D.T. & Early C.D. are composed of the following cells... what do they reabsorb/secreate?
1. Principal Cells-
2. Intercalated Cells-
1. Principal cells= Source of action of aldosterone which enchanches Na retention and promotes K secretion. ( - Princpial cells have receptors for aldoseterone and once activated reabsorb Na+, & Secrete K+)

2. Intercalated Cells= Reabsorb K+ & HCO3-, & Secrete H+ .... (also thought to be under aldosterone control)
Reabsorption of Water from the late distal tubules is controlled by?
Antidiuretic Hromone (ADH)
=> If ADH is present the water will be reabsorbed
What type of cells do Aldosterone Antagonists target? Why? examples of aldosterone antagonists?
=> Target Principal Cells bc Aldosterone antagonsist can act on IC receptors for Aldosterone in the Principal cells & block the action of Aldosterone; & therefore we do NOT have Increase Na+ Retention & Does NOT promote K+ Secretion === More Na+ in urine &Less K+ in Urine
=>Ex. of Aldosterone antagonists: Spironolactone & Eplerenone
What cells does Na+ channel blockers target and what do they do? Examples of Na channel blockers?
=> Block Na+ Channel w/in PRINCIPAL Cells & therefore lose more Na+ in the Urine
=> Ex of Na+ Channel Blockers: Amiloride & Triamterene
What acts in the Intercalated Cells of the Cortical Collecting Tubules and what does it do?
DOes K+ accumulated in the cell???
=> Aldosterone acts here to enhance H+ secretion & also have antiport= where H+ Ion is exchanged for K+ in cell.
=>K+ does NOT accumulate in the cell bc it can move into interstium by K+ channels of the basolateral secreations.
What des the NaK+ ATPase Pump in the basolateral area of tubular cells do for Na+ content in cell?
Keeps Na+ conten in cell LOW

Slide14 ppt 4
Where is the only place that there is an Increase in permeability of Urea and why?
Only in Medullary Collecting Duct (CT).
=> Permeable to urea Increased depends on osmolarity of this region=> concentrating urine.
=>> IF Highly Concentrated in Intersitium- then Causes Some Urea to Move OUT of Tubule into Interstiym.
In the medullary Collecting duct (CT) what does it activelyh reabsorb?
Secrete?
What is reabsorption of Water here controlled by?
=> Actively Reabsorb Na+
=>Secrete H+ ions->involved in regulation of acid-bas balance
=> Reabsorption of water here is controlled by ADH (when present)
Where can we concentrate our urine??? 2 places
1. Late Distal Tubules/ CD
2. Medullary Collecting Duct.
=> Under presence of ADH if ADH isn't there , then this is where urine is DILUTED
In the medullary collecting duct when can urea be passively reabsorbed?
In the case of Hypertonic interstium.
Summary of Tubular Reabsorption and Secretion:
1. PCT-
2. Thin Desc LoH-
3.Thick Asc LoH-
4. Early Distal Tubule-
5. Late Distal Tubule & CT-
6. Medullary CT-
1. PCT- 65% Reabsorption Filtrated
2. Thin Desc LoH- Water Reabsorption
3.Thick Asc LoH-Important Na2Cl transporter that is important in enhance osmolarity of intersitum. (25% of Na, Cl, K reabsorbed here)
4. Early Distal Tubule- Na Cl Active Transport
5. Late Distal Tubule & CT- In Presence of ADH H2O reabsorped & secretion of H+ & Activity of Aldosterone to enhance Na+ retention & K+ Secretion
6. Medullary CT- If ADH is plentiful H2O can be reabsorbed & in case of hypertonic interstium - urea can be passively reabsorbed (only place this happens)
Regulation of Tubular Reabsorption: The 4 regulators:
1. Glomerulotubular balance
2. Hormones ( mopstlu Aldosterone & ADH)
3. Sympathetic Nervous System
4. Arterial Pressure (pressure natiuresis)
Reg of Tubular Reabsorp:
1. Glomerulo tubular Balance:
=> Due to:
=> higher the filter load the= what toreabsorption and why?
=> Due to: Peritubular Capillary Physical Forces= Especailly Oncotic Pressure
=> Higher the filter load the more reabsortpiton of Na & Cl will take place. To keep more distal protions of nephron from becoming overloaded & to keep the ECF balance
Reg of Tubular Reabsorp:
1. Glomerulo tubular Balance:
=>Tubular Reabsorption Increase with what?
=>This mechanism conttributes to?
=>Tubular Reabsorption Increase w/ FILTERED LOAD (tubular filtered load= GFR x Ps). INcrease reabsorp in PCT. To not Overwhelm Distal portion of Nephrons.
=>This mechanism Contributes to: MAINTAING the ECFV.
Reg of Tubular Reabsorp:
1. Glomerulo tubular Balance:
Importance of Glomerulotubular Balance in Minimizing changes in ECFV: ( & importanc of "Perfect" glomerulotubular balance"
=>Increase GFR bc increase in filtered load of fluid.
=> if don't have Glomerulotubular balance the reabsorption is going to remain as is whe u didn't have excess fluid & reabsorption would be lower.
=>BUT bc of "perfect" glomerulotubular balnce = increased GFR most will be reabsorbed so urine volume will be the same.
Reg of Tubular Reabsorp:
2. Hormones- 5 - 2 most important??
1.Aldosterone
2.Angiotensin 2
3. Antidiuretic Hormone (ADH)
4. Natiuretic Hormones (ANF) ( increase in na loss ANP)
5. Parathyroid Hormone
(2 most important: Aldosterone & ADH)
Reg of Tubular Reabsorp:
2. Hormones;
=>Aldosterone Actions on Late Distal, Cortical, & medullary Collecting Tubules: on Na, K and H
1. INcreases Na+ Reabsorption= Principal cells
2. Increases K+ Secretion= Prinscipal Cells
3. Increases H+ Secretion= Intercalated Cells
Reg of Tubular Reabsorp:
2. Hormones
=>Aldosterone Actions on Late Distal, Cortical, & medullary Collecting Tubules:
Aldosterone actons on what receptors in target cells & = what which does what?
Aldosterone
+ (acts on)
Inttercellular Minal corticoid receptor in target cells
_______________________
=Changes in Gene Expression ( & promotes effect ... ex: if its Na+ retention then promotes K+ secretion)
Reg of Tubular Reabsorp:2. Hormones
=> Control of ALDOSTERONE SECRETION:
Factors that INCREASE Aldosterone Secretion: 3
1. Angiotensin 2 ( acts directly on zona glomerousa of adrenal gland to enhance aldosterone release)
2. Increased Plasma K+ -(Dietary K= eat 15 bananas = ^ plasma K so stimulates aladosterone)
3. Adrenocorticotrophic Hormone (ACTH) - Permissive Role - (From pituatary normally stimulates adrenal gland but doesn't have much effect on outer zona glomerousa that contains aldosteron, so doesn't play a major role in regulation of aldosterone)
Reg of Tubular Reabsorp:2. Hormones
=> Control of ALDOSTERONE SECRETION:
Factors that DECREASE Aldosterone Secretion: 2
1. Atrial Natriutertic Factor (ANF) (ANP) -(peptide hormone produced by the cardiac atria- increase ECFV= stretches receptors in atria which ^ production of ANF(P) & thereby causes INHIBITION of Aldosterone & an ^ in LOSS of Na+!)
2. Increased Na+ Concentration (Osmolality) -(bv- decreased further aldostertone release)
Reg of Tubular Reabsorp:2. Hormones:
=>Angiotensis 2:
A. _____ Na+ & Water Reabsoption
B. Stimulates _______ Prodcution by:
C.Directly ____ Na+ Reabsorption
D. ______ Efferent Arterioles & _______ Peritubular Capillary Reabsorption
i._____ Peritubular Cap Hydrostatic pressure
ii. _____ Filtration fraction, thereby ______ pertibular oncotic pressure; bc:
=>Angiotensis 2:
A. _INCREASE_ Na+ & Water Reabsoption
B. Stimulates _ALDOSTERONE_ Prodcution by: adrenal gland
C.Directly _INCREASES_ Na+ Reabsorption ( PCT, LoH, Distal, CT)
D. _CONSTRICTS_ Efferent Arterioles & _ENHANCES_ Peritubular Capillary Reabsorption
i._DECREASED_ Peritubular Cap Hydrostatic pressure
ii. _INCREASED_ Filtration fraction, thereby _INCREASING_ pertibular oncotic pressure; bc: ^ GFR= more protein available, so ^ plasma oncotic pressure & ^ reabsorption
(A-2: Asp-Arg-Val-Tyr-Ile-His-Pro-Phe)
Reg of Tubular Reabsorp:2. Hormones
Angiotensin 2 Constriction of Efferent Arteriloles Cause ___ yet Maintains what?
Causes Na+ RETENTION, yet MAINTAINS WASTE PRODUCT EXCRETION
Reg of Tubular Reabsorp:2. Hormones
=>Atrial Natriuretic Peptide (ANP)
A. ____ Na+ Excretion
B. Secreted by ____ ____ in response to _______ (_____ Blood Volume)
C. Directly _____ Na+ Reabsorption
D. _____ Renin Release & Aldosterone Formation
E. ____ GFR- by dilating Afferent Glomerular Arteriole
F. Helps to _____ Blood Vol. Expansion.
=>Atrial Natriuretic Peptide (ANP)
A. _INCREASES_ Na+ Excretion
B. Secreted by _CARDIAC ATRIA_ in response to _STRETCH_ (_INCREASED_ Blood Volume)
C. Directly _INHIBITS_ Na+ Reabsorption
D. _INHIBITS_ Renin Release & Aldosterone Formation
E. _INCREASES_ GFR- by dilating Afferent Glomerular Arteriole
F. Helps to _MINIMIZE_ Blood Vol. Expansion.
Reg of Tubular Reabsorp:2. Hormones
=>Atrial Natriuretic Peptide (ANP)
- The Overall Effect of ANP onthe Body is to???
Counter Increases in BP & Vol. caused by Renin-Angiotensis System.
(ANP counters the effects of renin-angiotensin)
**** LOOK AT SLIDE 25 PPT 4****
Reg of Tubular Reabsorp:2. Hormones
=> What is Aldosterone Infusion dueto?
=>What is Aldosterone "Escape" Due to?
=>1st- aldosterone Infusion is due to constant enhanced Na Retention.
=>ESCAPE= Due to w. enhanced Na+ retention over a period of time will stimulate an INcrease in Blood Vol. which will stimulate ANP release from the Cardia Atria & this INHIBITS Action of Aldosterone, therefore is responsible for ALdosterone Escape.
(Aldosterone "Escape"- due to Increasing ANP)
**** LOOK AT SLIDE 26 in PPT 4*****
Reg of Tubular Reabsorp:
3. Sympathetic Nervous System
A. Directly ____ Na+ Reabsorption
B.Stimulates Renin ____
C.____ GFR & RBF
Sympathetic Nervous System
A. Directly _INCREASES(STIMULATES)_ Na+ Reabsorption
B.Stimulates Renin _RELEASE_
C._DECREASES_ GFR & RBF
Reg of Tubular Reabsorp:
3. Sympathetic Nervous
These are responses to HEART Failure that are _____ of ANF/ANP
OPPOSITE
=> In sress of Cardiac heart failure we get Low C.O., enhanced peripheral venous congetion.
=> Low C.O. interprtted by kidney by neeeding more:.... ^GFR & RBF to Kidney, so trys to respond by enhancing Blood flow.
Reg of Tubular Reabsorp:
4. Arterial Pressure (PressureNatriuesus )
=>Increased Arterial Pressure, ______ Na+ Reabsorption (Pressure Natriuresis)
A. = ____ Na+ & H2O Loss Associtated
B. _____Peritubular Capillary Hydrostatic pressure
C. _____ Renin & Aldosterone
D. ____ Release of Intrarenal Natriuretic Factors like Prostaglandins.
=>Increased Arterial Pressure, _DECREASES_ Na+ Reabsorption (Pressure Natriuresis)
A. = _INCREASED_ Na+ & H2O Loss Associated ( To Balance Out ECF w/out Overwhelming ECF & C.O.)
B. _INCREASED_Peritubular Capillary Hydrostatic pressure (Resists REabsorbtion)
C. _DECREASED_ Renin & Aldosterone
D. _INCREASED_ Release of Intrarenal Natriuretic Factors like Prostaglandins. ( Causes Vasodilation & Loss of Na)
Reg of Tubular Reabsorp:
4.Aterial Pressure
Renal Pressure Natiuresis is ______ of SNS & hormones bc?
INDEPENDENT of SNS & Hormones BC it can be seen in an isolated Kidney
Reg of Tubular Reabsorp:
4.Aterial Pressure
Chronic vs acute elevation of Bp in Renal Pressure Natriuresis.
- W/ Chronic Elevations: ALdosterone & A2 are ??
W/Chronic Elevations: Aldosterone & A2 are SUPPRESSED, SO the PRESSURE DIURESIS MECHANISM is NOT Dampened.
=> Chronic - Reduced A2 & Aldo, Lead to Increased K+ output via Increase MAP
Normal Renal Tubular Na+ Reabsorption. ( check out slide 30 ppt 4)
A. Excretion of 150mEq Na+/day corresponds to the consumption of ___ g table salt.
B. USRDA for Na+ is ____
C. Low Na+ Diet
D. 1ox bag of chips contians about _____mg Na+.
E. Increase Na+ Content & load contributes to ??
A. Excretion of 150mEq Na+/day corresponds to the consumption of _8.8_ g table salt.
B. USRDA for Na+ is _2500mg (7.4g table salt, 1.25 tsp)_
C. Low Na+ Diet is _1500mg ( 3.5g Table Salt).
D. 1oz bag of chips contains about _170_mg Na+.
E. Increase Na+ Content & load contributes to: OBESITY & HYPERTENSION
Peritubular Capillary Reabsorption.
Pif= 6
Pc= 13
(Pi)if= 15
(Pi)C=32
Filtration=
Absorption=
Net =
Filtration= Pc + (Pi)if = 13 + 15= 28
Absorption= Pif +(Pi)c = 6+32= 38
SO- 38-28=10
NET REABSORPTION PRessure= 10 (The higher the # the more absorbed/filtrated)
Bc the plasma in the peritubular capillary lost 20% of water as it passed through the glomerulus, the protein concentraion ^ by 25%.
To optimize Filtration in Glomerular Capillaries, Want ______ Glomerular Cap Hydrostatic pressure & _____ Interstial Pressure.
To optimize Filtration in Glomerular Capillaries, Want _HIGH_ Glomerular Cap Hydrostatic pressure & _LOW_ Interstial Pressure.
To Optimized RESORPTION in PEritubular Capillaries want _____ Intersitial Hydrostaic pressure, _____ Capillary Collloid Osomotic Pressure & ___ Capillary Hydrostatic Pressure.
To Optimized RESORPTION in Peritubular Capillaries want _HIGH_ Intersitial Hydrostaic Pressure, _HIGH_ Capillary Collloid Osomotic Pressure & _LOW_ Capillary Hydrostatic Pressure.
Tubular Secretion:
A. 1st Step:
B. Entry into or Exit from Tubular cells can be :
C. Exit from toTubular cell to ___
D. Ex:5
Tubular Secretion:
A. 1st Step: Simple diffusion from (blood in) Peritubular Capillaire to Intersitial Fluid
B. Entry into or Exit from Tubular cells can be : ACTIVE or PASSIVE
C. Exit from toTubular cell to _LUMEN_
D. Ex: K+, H+, Organic Acids, Organic Bases, NH3
Why is PCT Source of lot of Secretion?
BC That's where filtration 1st meets Tubular Cells & Where we Want to get rid of Toxic/ Drugs as quickly as possible.
Calculation of Tubular Secretion.
Secretion (into Tubules)=
Secretion (into tubules)= Amt. Excretion - Amt. Filtraion
Secretion(s)= (Us xV) -(GFR x Ps)
1. Secretion(s)=
2. Filtration(s)=
3.Excretion(s) =
1. Secretion(s)= [ U(s) x V] - [GFR x P(s)]
2. Filtration(s)= GFR x P(s)
3.Excretion(s) = U(s) X V
What can you tell from Specific Gravity & what does Specific gravity measure/what is it?
=> Can tell How CONCENTRATED your URINE is.
=>Bc Specific Gravity = # of Active Particles & Weight of Osmolarity
What is the Max & Min Urine Concentration in Humans? (*& specific gravity)
Max Urine Concentration: 1200- 1400 mOsm/L (Specific gravity ~1.030 = high)
Min Urine Concentration: 50-70 mOsm/L (Specific Gravity ~1.003 = low)
Kidneys can differeinated between Concentrated & diluted urine. This is important bc if kidney problems want to keep urine urine:
Concentrated
But if drink a a lot of soda want to Dilute urine= Kidney can discrete very dilute ureinw/out much solutes can absorb or not absorb water.
A. Urine Osmolarity is based on:
B. Specific Gravity is based on:
A. Urine Osmolarity is based on: # of Acting Osm Particles
B. Specific Gravity is based on: # of Particles + Weight
What can cause a false reading/ super concentrated urine reading?
Glucose or Protein in urine Bc high specific gravidy bud doesn't dissociate weighs a lot
IF drink 1.L of H2O, Urine Osmalirity Decreases, Urine Flow Rate INncreases, but Plasma Osm doesn't change,= Do NOT excrete OSm just watery urine this is done by:
1. Continue Electrolyte Reabsorption
2.Decrease water Reabsorption.
(electrolytes absorbed, but H2O not absorbed - go to CT & out bc NO ADH)
IF drink 1.L of H2O, Urine Osm Decr, Urine Flow Rate ^, but Plasma Osm doesn't change,= Do NOT excrete OSm just watery urine this is done by Electrolytes being absorbed but not H2O Bc of what (mech.)?
DECREASE ADH Release, thereby reducing water permeability in distal& Collecting tubules. This is bc stimulus is ^Osm of blood (Posm) is NOT present , so NO ADH, So NO Enhanced Reabsorption of H2O in Distal CT/Medullary Ducts= Very Dilute Urine & Osmolarity of around 50-70 NO SOLUTES RELEASED IN URINE!
The Minimum Urine vol in chich ingested solutes can be dissolved & excreated ( to keep electrolyte balance) THis is known as??
Obligatory Urine Volume
If Max urine osm is 1200 mOsm/L, & 600mOsm of Solute must be Excreted each day to Maintain electrolyte balance, the Obligatory Urine Volume is?
=> What is NOrmal??
[600mOsm/d] / [1200mOsm/L] = 0.5L/day
=> NORMAL is 1L to 1.5 L
(Max urine osm / solute must be excreted each day)
What Determins the obligatory urine vol?
Max Urine Osmolarity
In renal ds the obligatory urine volume may be ______ due to what?
May be INCREASED due to Impaired Urine Concentrating Ability
If the Max urine Osm= 300mOsm/L (renal failure) & 600 mOsm of solute must be excreted each day to maintain electrolyte balance, what is the Obligatory urine Volume?
[600mOsm/d] / 300mOsm/L = 2.0L/day
In Renal Failure run into problems bot able to ______ urine but need to ______ _____ in urine try to ??
In Renal Failure run into problems bot able to _CONCENTRATE_ urine but need to _SECRETE SOLUTES_ in urine try to: INCREASE URINE VOL. but sometimes don't REach it.
Formation of Concentrated Urine:
Stragey:
1. Continue Electrolye reabsorption
2. Increase water reabsoprtion (through ADH)
What is the mechanism/ how do we contrate urine from electrolyte and water reabsorption?
1. Increased ADH release to Increase Water Permeability in Distal & Medullary Collecting Tubules.
2. High Osmolality of Renal Medullua (interstium required bc stimulates H2O reasorp bc h2o moves high to low & further contrates urine.
3. Countercurrent flow of Tubular Fluid ( one way then other way as flow tubules fluid concentration assumes concetration= osm as renal medullary interstitium becomes MOre & more concentrated as more fluid is moved through bc in thick asc limb have this nacl, k co trasnporter not absorb electroylytes but move to medullary area but not h2o.
ADH/ AVP
1. Produced/ Synthesized in:
2. Secreted by:
3._____ H2O Permeability & Reabsorption in Distal & Collecting Tubules
4. Allows differential control of:
5. Important congroller of:
ADH/ AVP
1. Produced/ Synthesized in: HYPOTHALMUS
2. Secreted by:POSTERIOR PITUITARY
3._INCREASES_ H2O Permeability & Reabsorption in Distal & Collecting Tubules
4. Allows differential control of: H20/WATERY URINE &SOLUTE EXCRETION
5. Important controller of: ECF OSMOLARITY
What is the mechanism of action for AVP/ADH?
ADH interatcts w/ its receptor(Vasopressin 2 receptor= V2 receptor) on the Medullary CT or Ditstal CT cells => stimulates cAMP & thereby Protein Kinase. Protein Kinase is responsible for synthesis of new Aquaporin 2 channels, they are inserted in the apical membrane of these cells. Once inserted these Aquaporin 2 channels can quickly absorb any H2O right into cell & then via Aquaporin 3 channels between the cells & H2O moves quickly into interstium. So we can quickly reabsorb H2O Via ADH/AVP.
Solute accumulation in the renal medulla by "COUNTERCURRENT MULTIPLICATION" due to 4 things: active transport and passive diffusion, and diffusion
1. Active transport of Na, K,Cl & other ions from Thick Asc LoH into Medullary Interstitium.
2. Active Transport of ions from Medullary CD into Interstitium (Hypertonicity of med.intersitium by electrolytes falls down into it)
3. Passive Diffusion of urea from Medullary CD into Interstitium.
4.Diffusion of only sm amts of H2O into Medullary Interstitium.
(movement of Urea= Increase Osm of medullary intersitum enahched medullary osmolarity of intersitium)
Loop Diuretics bloock cotransport in thick asc. LoH = Can't Concentrat urine bc Thick Asc LoH significantly contributes to the:
INCREASED Tonicity of Medullary Interstium
Ability to concentrate urine relies on:
Also, REnal Interstium remains hyperosmotic via this:
COUNTER CURRENT MULTIPLER MECHANISM
Countercurrent multipler mech depends on:
Anatomical relationships of LoH, Vasa Recta & Collecting Ducts (all parallel to each other)
Countercurrent multipler mech:
Filtrate in Asc & desc limbs of LoH flows in what direction?
Opposite Directions (counter current)
Countercurrent multipler mech
___% of nephrons in kidney are juxtamedullary w/ ___ LoH. Extend into renal medulla parallel to ____ & ____
_25_% of nephrons in kidney are juxtamedullary w/ _LONG_ LoH. Extend into renal medulla parallel to _VASA RECTA_ & _COLLECTING DUCTS_
(Vasa Recta= long vessels= slow low flow contribute to hypertonicity in medulla as well)
Countercurrent multipler mech
1. Continous deleivery of ____ from PCT into ___..
2.Continuous Resorption of ____ into Interstitium by _____.
3.Na-K pumps pump Nainto Interstitium to _____ Osmolarity.=> formation of ____
Countercurrent multipler mech
1. Continous deleivery of _NaCl_ from PCT into _LoH_..
2.Continuous Resorption of _NaCl_ into Interstitium by _THICK ASC. LIMB_.
3.Na-K pumps pump Na into Interstitium to _INCREASE_ Osmolarity.( to ~1,200mOsm/L) => formation of _INTERSTITIAL OSMOLAR GRADIENT_
In medullary tubules more water is reabsorbed bc ____ is present, so adds to _______ of medullary interstium= very ______ urine.
In medullary tubules more water is reabsorbed bc _ADH_ is present, so adds to _HYPERTONICITY_ of medullary interstium= very _CONCENTRATED_ urine.
Countercurrent multipler mech
1.Blood Vessels of Vasa Recta surround ____ & ____
2.Blood w/in Vasa Recta concentrated after filration w high _______ pressure.
3.Water resprbed by distal CT under effect of ADH to _____ urine.
Countercurrent multipler mech
1.Blood Vessels of Vasa Recta surround _LoH_ & _MEDULLARY COLLECTING TUBULES _ (bloid flow ver low/slow)
2.Blood w/in Vasa Recta concentrated after filration w high _PLASMA COLLOID ONCOTIC_ pressure.
3.Water resprbed by distal CT under effect of ADH to _CONCENTRATED_ urine.
Countercurrent multipler mech:
1. Vasa Recta perserve the ______ of the Renal Medulla
2. Vasa Recta serve as _____ exchangers
3. Vasa Recta Blood Flow is __
4.Vasa Recta mimic ___, as moves on more concentrated bc solute moves ___ and H2O moves ___.
4.As coming back up more &more H2O comes ____ to _____ the content, ____ hydrostaic pressure & more & more solute is pushed ___ of vasa recta into ____.
1. Vasa Recta perserve the _HYPEROSMOLARITY_ of the Renal Medulla
2. Vasa Recta serve as _COUNTERCURRENT_ exchangers
3. Vasa Recta Blood Flow is _LOW (only 1-2% of total RBF)_
4.Vasa Recta mimic _Loh_, as moves on more concentrated bc solute moves _IN_ and H2O moves _OUT_.
4.As coming back up more &more H2O comes _IN_ to _DILUTE_ the content, _INCREASE_ hydrostaic pressure & more & more solute is pushed _OUT_ of vasa recta into _INTERSTIUM_.
Why is it called Countercurrent Exchange in vasa recta?
Bc Vasa Recta are in parallel w/each other so movement of solute out of asc limb will descend into another vasa recta descending. More of it is exchanged,.
-High osm of blood in vasa recta is maintained to support & to maintain high hypertoinicy medullary interstum. IF Increase BF this washes out ability to concentrate urine
What are the NET Effects of Countercurrent Multiplier?
1.More ___ than ___ is added to the Renal Medulla.
2. Fluid in the Ascending loop is _____.
3. Most of the water reabsorption occurs in the ___ rather than in the _____.
4.Horizontal gradient of solute concentration established by the :
1.More _SOLUTE_ than _WATER_ is added to the Renal Medulla. (ex: Solutes are "trapped" in renal Medulla= makes it very hypertonic)
2. Fluid in the Ascending loop is _DILUTED_. (bc electrolytes reabsorbed)
3. Most of the water reabsorption occurs in the _CORTEX_ rather than in the _MEDULLA_. (ex, in PCT & DCT)
4.Horizontal gradient of solute concentration established by the : ACTIVE PUMPING of NaCl is "Multiplied" by Countercurrent Flow of Fluid.
=> W/pressence of ADH Water reabsorption is _____.
=>Also, ADH _____ the permeability of Urea -_____ ______ into the ________ Medullary Intersitum . This ___ the overall Tonicity of the Meddullary intersitium & promotes more____ reabsorption = _____ urine.
=> W/pressence of ADH Water reabsorption is _INCREASED_.
=>Also, ADH _ENHANCES_ the permeability of Urea -_PASSIVE DIFFUSION_ into the _HYPERTONIC_ Medullary Intersitum . This _INCREASES_ the overall Tonicity of the Medullary intersitium & promotes more_H2O_ reabsorption = _CONCENTRATED_ urine.
Urea Recirculation:
1.Urea is ____ _____ into PCT, but 1' excreted through.
2.In presence of ADH, H2O is reabsorbed in distal & CT, concentrating urea in ____ parts of the _____.
3. The ___ ____ ___ ___ Is Highly permeable to Urea, which diffuses into the Medullary Interstitium.
4.ADH ____ Urea permeability of Medullary collecting tubule.
Urea Recirculation:
1.Urea is _PASSIVELY REABSORBED_ into PCT, but 1' excreted through.
2.In presence of ADH, H2O is reabsorbed in distal & CT, concentrating urea in _THESE_ parts of the _NEPHRON_.
3. The _INNER MEDULLARY COLLECTING TUBULE_ Is Highly permeable to Urea, which diffuses into the Medullary Interstitium.
4.ADH _INCREASES_ Urea permeability of Medullary collecting tubule.
If in renal failure can kidneys excrete urea>
NO< which leads to renal poisioning, coma & death.
=> Usuallly excrete enough urea to keep in balance w/plasma concentration of urea.
Ultimate rate of Urea excretion is determined by 2 factors:
1. GFR ( if iNcrease GFR, not a lot of urea absorption bc flow rate too quick)
2. Concentration of Urea in plasma => Abnormal elevation of urea in plasam= UREMIA(prevent elevation of urea in plasma )
Medulllary interstitium remains hypertonic via??
1. Active transport of Na & co transport of K, cl, etc from thick asc LoH (impermeable to H2O) into medullary interstitium.
2. Active transport of ions from CD into medullary interstitium ( raises renal medullary interstitium osmolarity to ~1200)
3. Passive diffusion of urea from medullary CD into medullary interstitium.
4. H2O resorption by DCT & Medullary CD in cortex under influence of ADH
Summary of Water Reabsorption & Osmolarity in Different Parts of Tubule:
1. PCT:
2.Desc. LoH:
3.Asc. LoH:
4.Early Distal;
5. Late Distal & coll. Tubules:
6. Medullary CD:
Summary of Water Reabsorption & Osmolarity in Different Parts of Tubule:
1. PCT: 65% Reabsorption, Isosmotic
2.Desc. LoH: 15% reasorption, Osmolarity Increases
3.Asc. LoH: 0% reabsorption, Osmolarity Decreases
4.Early Distal: 0% Reabsorption, osmolarity Decreases
5. Late Distal & coll. Tubules: ADH dependent water reabsorption & tubular osmolarity
6. Medullary CD: ADH dependent water reabsorption & tubular osmolarity
"Free" water Clearance C(H2O)=
C(h2o) = V - [(Uosm x V) / Posm]
Uosm= urine osmolarity
V= urine Flow rate
Posm= Plasma osmolarity
If Uosm is <Posm =
Dilute urine , C(h2o)= +
If Uosm is >Posm=
Concentrated urine, C(h2o)= -
With an average solute excretion rate of 900mOsm/day (Cosm= 3L/d) & minimal urine osm of 50mosm/kg. what is the C(H2O)??
Volume= 900/ 50= 18 L/d
C(H2O)= 18L - 3L = 15 Lday
If aver solute excretion rate of 900mosmday
Cosm= 3L/d
& max urie osmolarity = 1200 mosm/kg.. what is C(H2O)?
Volume= 900/1200= .75L/d
C(H2O)= .75 - 3= -2.25L/day
=> wont excretat any free water clearance if really concentrated.
When drink pure water you:
____ in urine flow
_____ in Posm
When drink pure water you:
_INCREASE_ in urine flow
_DECREASE_ in Posm ( bc diluting osm.
What is the ADH- Thirst Osmoreceptor System mechanism?
Increased EC osm (NaCl) stimulates ADH release, which Increases H2O reabsorption, & stimulates thirst (intake of water).
(By inserting aquaporinin channels= facillitates)
What is the major stimulus of ADH release from posterior pituitary?
Small Change in Posm ( as little as 1% increase)
ADH Synthesis in the _______ Neurons of _______. (responds well to osmoreceptros small changes in Posm), Release by the ________, & action on the _______.
ADH Synthesis in the _MAGNOCELLULAR_ Neurons of _HYPOTHALMUS_. (responds well to osmoreceptros small changes in Posm), Release by the _POSTERIOR PITUITATRY_, & action on the _KIDNEYS_.
Other than a small change in Posm what else can stimulate ADH reelesae... but no here near as strong of a stimulus?
Baroreceptors.. Decrease in BP & BV more than 10% an increase ADH
What are the 4/8 Stimuli for ADH Secretion?
1. Increased osmolarity (mostly)
2. Decreased blood Volume (more than 10%) = Cardiopulmonary reflexes
3. Decreased BP (Arterial baroreceptors)
4. Other Stimui:
a.Input from Cerebral cortex (fear)
b.Angiotensin 2 (not really but 1' role stimulating thirst)
c.nausea= vomiting
d. Nicotine= (ADH enhances reabsorption of H2O & Decreasessalivary secretion, Sokers have lower salivary secretions thatn non smokers
e. Morphine- can induce nausa
Osmoreceptor- ADH / Thirst Mechanism:
ADH Sys, water deficit=> ___ in Na & ECF Osm=>_____ of Osmoreceptor cells in ____ ______ => release of _____ from posterior pituitary.
ADH Sys, water deficit=> _INCREASE_ in Na & ECF Osm=>_SHRINKAGE_ of Osmoreceptor cells in _ANT. HYPOTHALAMUS_ => release of _ADH_ from posterior pituitary
Osmoreceptor- ADH / Thirst Mechanism:
1. ADH increases permability of _____ & _____ to H2O.(allows reabsorption of water) & ____ urine Vol., but does not alter excretion of _____ vol.=> ___ concentration of urine& water conservation.
2. Excesss water (over drinking)=> ____ of osmoreceptor cells=> ____ ADH & Lg volume of ___ urine.
1. ADH increases permability of _DCT_ & _CD_ to H2O.(allows reabsorption of water) & _DECREASED_ urine Vol., but does not alter excretion of _SOLUTE_ vol.=> _INCREASE_ concentration of urine& water conservation.
2. Excesss water (over drinking)=> _SWELLING_ of osmoreceptor cells=> _DECREASES_ ADH & Lg volume of _DILUTE_ urine.
Factors that Decrease ADH Secretion;
1. 2. 3.
4. Other factors- 3
1. Decreased osmolarity
2. Increased Blood Vol. (Cardiopulmonary Reflex)
3. Increased BP (Arterial Baroreceptors)
4.Other Factors:
a. Alcohol= Inhibits ADH bc alocohol is toxic- need to flush it from body. Ethanol Decreased ADH secretion.
b.Clonidine (alpha2 adrenergic agonist)- antihypertensive= Decrease sympathetic outflow from CNS which Decreases constrict & Increases Vasodilation.
c. Haloperidol (antipsychotic, tics, tourette's) -
Average GFR =
Average Tubular Resorption=
Average Urine Excretion=
Average GFR = 180 L/day
Average Tubular Resorption= 178.5 L/day
Average Urine Excretion=1.5 L/day
Small changes in GFR can cause large changes in _____ _____.
All fb mech that control renal excretion of Na & H2O alter either ____ or _____ ____.
Small changes in GFR can cause large changes in _RENAL EXCRETION_.
All fb mech that control renal excretion of Na & H2O alter either _GFR_ or _TUBULAR RESORPTION_.
In Pressure Natriuresis - Increase BP=
Increase Na Excretion
In Pressure Diuresis - Increased BP=
Increase in Urine Volume
Both Pressure Natriuresis and Diuresis are used in long term control of ???

check out additional info on slides 15&16 ppt 6****
BP & Regulation of Body Fluid Volume
In Chronic hypertension, Failure of Kidneys to successfully excrete salt & water at normal pressures =>
INCREASED BP
What is the common Tx with natriuretics & diuretics to DECREASE Blood Volume & BP?
By DECREASING Salt & Water Retention. (diuretics - Increase Na+&H2O loss)
What are 2 basic requirements for secretion of concentrated urine?
1. High ADH
2. High Osmolarity of Renal Interstitium
What is the efect of increasins Na+ intake on urinary sodium excretion and ECVF? What may this lead to?
Increase Na+ intake= Increase ECFV but after a while bc of this hypertonicity of ECFV expansion there will be a Na+loss.
ECFV expansion may eventually increase BP & may lead to a pressure natriuesis or direusis after a few days... takes a few days.
What is the effect of changes in Na intake on plasama sodium after blocking aldosterone (or ANG2)?
Balanced pretty well. Not much effect ANg2 aldosterone system. Not very important in Na+ regulation,.,... What is important is the ADH Thirst Mechanism , that is what regulates NA.
What factors affect thirst.. or cause thirst? 5.
1. Increase Osmolarity of CSF (promotes drinking stimulate water intake)
2 Decrease Blood Volume (Cardiopulmonary reflexes) or Decrease in ECFV
3. Decrease BP (arterial baroreceptors)
4. Angiotensin 2= Direct to Increase H2O intake & thirst
5. Dryness of mouth ( waterlow in body- salivary secretion slows down, 1st thing that dries out is mouth=due to salivary secretions) & Gastric Distention ( shortterm control= Decrease fluid intake)
1.What is the Thirst Mechanism activated by?
2. What is referred to as the threshold for drinking?
1. Thirst mech activated when Na in ECF Increases.
2. THreshold for drinking. ~2mEq/L>normal
Where is the Thrirst mechanism located?
In the same area of brain along 3rd ventricle that promotes ADH secretion also stimulates thirst. ( drinking dilutes ECF & Decreases osmolarity)
How does increase ECF stimulate thirst?
INcrease ECF=> IC Dehydration & shirinkage of Receptor Cells in Thirst Center => Stimulates Thirst (just like hypothalmus & ADH)
Decrease in EC ____ & Decrease in ___ or ____ elicit both Thirst response & salt appetite.
Decrease in EC _Na_ & Decrease in _BV_ or _BP_ elicit both Thirst response & salt appetite.
ADH produced by post. pituitary ____ H2O resorption by ___ permeability of DCT's & CD=> ____ _____
ADH produced by post. pituitary _INCREASES_ H2O resorption by _INCREASING_ permeability of DCT's & CD=> _H2O CONSERVATION_
1. Dehydration=> __ ADH
2. Overhydration=> __ADH
1. Dehydration=> _INCREASE_ ADH
2. Overhydration=> _DECREASE_ADH => Decrease reabsorbtion => Increased Urine Output
In severe dehydration, high ADH levels can ___ ECF Na.
In severe dehydration, high ADH levels can _DECREASE_ ECF Na
(INCREASE ^^ REsorption of H2O=> Dilute ECF & ^BP => ^Na Excretion
ADH Secretion stimulated by: Decrease in 2 things?
1. Decrease Aterial Pressure
2. Decrease Blood Volume
1. Nausea, some drugs like nicotine & morphine- ____ ADH
2.Alcohol __ ADH
1. Nausea, some drugs like nicotine & morphine- _INCREASES_ ADH
2.Alcohol _INHIBITS_ ADH
Because alcohol (ethanol) Decreases ADH = _____ times needing to urinate. This is fixed by?
Increases times needed to pee, but if Increase salt/ peanuts then helps decrease the # of trips to the bathroom
If intake 1L (3 beers)/hr to maintain water balance, urinary flow must:
Increase to 1l/hr.
If intake 1L (3 beers)/hr to maintain water balance, urinary flow must:Increase to 1l/hr. How does this happen?
=>ECFV expands + MAP ^ => Contribute to Inhibiting ADH secretion.
=> Posm Increases (due to ethanol),
=>Ethanol inhibits ADH secretion
=> As P(adh) Declines, collecting duct water reabsorbtion declines & urinary flow INcreases
(Bc of inhibition of ADH (by ethanol) & ECFV expansion & ^ MAP = Causes ^ Urine Flow)
What is Diabetes Insipidus and what are the 2 types>
Diabetes insipidus= DECREASE in ADH Production.
Diabietes insipidus -2 types of Inappropriate secretions of ADH:
1. Central
2. Nephrogenic
What is "Central" Diabetes inspidius due to?
=> Results in what?
=> Clinical Sx include? 2
Central= Inability of Posterior Pituitary to Produce ADH (ex head injures)
=> Results in: Production of Lg vol. dilute Urine
=> Clinical Sx: Polyuria/Polydypsia (PU/PD)
What is Nephrogenic Diabetes Insipidus due to?
Nephrongenic Due to:
1. Inability of Renal Tubules to respond to ADH
2. Impairment of Counter-Current Mechanism
ANP is secreted by___ ___ ___ when ____ excessively _____ (ex: due to increase ____ ___)=> ___ GFR => ___ excretion of ____ & ____
ANP is secreted by_SPECIALIZED ATRIAL CELLS_ when _ATRIA_ excessively _DISTENDED_ (ex: due to increase _BLOOD VOLUME_)=> _INCREASE_ GFR => _INCREASE_ excretion of _Na+_ & _H2O_
ANP is secreted by spec atrial cells when atria excessively distend (ex due to ^ BV)=> ^GFR=>^Excetion of Na & H2O=
WHAT does this do with urine production & blood vol. ... similar to what?
=>Increases Urine Production
=>Decreases Blood Vol.
=> Similar to Pressure Natriuresis & Diuresis (a relitively minor effect used for fine-tuning blood vol)??
Inappropriate ADH Syndrom is and leads to?
Excess ADH leads t:
1. Excess Water Reabsorption
2. Decreased Plasma Osmolarity
3. Hyponatremia
What is insufficient ADH that leads to: Water loss, Increased Plasma Osmolarity, Hypernatremia, & Excess Thirst?
"Central" Diabetes Insipidus
Failure to Produce or Release ADH is what disorder?
"Central Diabetes Insipidus"
(Depressed P(adh))
Failure to respond to ADH is what disorder?
"Nephrogenic Diabetes
Failure to respond to ADH : "Nephrogenic Diabestes insipidus can be caused but what 5 things?
1. Defect in ADH action
2. Impaired loop NaCL Reabs. (loop diuretics possible involvement)
3. Drug induced Renal Damage: (lithium (bipolar- impair ability to have normal countercurrent mech) or Analgesics)
4.Malnutrition (decreased urea concentration) (decreases Posm)
5. (Other) Kidney Disease: Pyelonephritis, hydronephrosis, chronic renal failure
What are the 3 types of DI (diabetes insipidus)?
1. Hypothalmic or central D.I.
2. Nephrogenic D.I.
3. Polydipsic D.I.
What DI is a defect in ADH action; failure to maintain hyperosmotic medullary gradient. (associated failure of kidney to respond to normal or high ADH levels eiter due to receptor defect of kidney affect it self unable to maintain hyperosmotic medullary gradient)
NEPHROGENIC D.I.
What is the D.I. that is associtated with Compulsive water drinking=> exceed the physiologica need and really dilute urine all of the time??
POLYDIPSIC D.I. (many drinking)q
What is the D.I. that is a defect in ADH synthesis (secretion) or release and has Depressed P(adh)?
Hypothalamic or Central D.I.
Based on the following symptoms does the Pt. have Central or Nephrogenic D.I?
1.Polyuria, Fluid Restriction Results in HYPERNATREMIA w/LOW Plasma ADH, NO ^ in Urine Osm.
-Pt. Responds to ADH adminstration w/ Reduced urine Output, Increased urine Osmolality.
-Treatment: water acces, ADH
CENTRAL DI
Based on the following symptoms does the Pt. have Central or Nephrogenic D.I?
1.Polyuria, Fluid Restriction Results in HYPERNATRIMA w/ELEVATED Plasma ADH
2. NO Response to ADH
3. Treatment: Correct underlying renal disorder if possible, low sodium diet + Diuretic enhance Na+ Excretion.
NEPHROGENIC DI
1.DOes Nephrogenic or Central DI respond to ADH?
2. Which one has elevated plasma ADH? low?
1. Central D.I. REsponds to ADH- W/ REduced Urine Output, Increased Urine Osmolality.
2. Nephrogenic D.I.= Elevated Plasma ADH
Central D.I.= Low Plasma ADH
How do your treat a pt. with Central D.i?
Water access, ADH
How do you treat a pt. with Nephrogenic D.I.?
Correct underlying renal disorder if possible, then put on Low Sodium diet + Diuretic to enhance Na Secretion
Pt. w/Polydipsic DI presents w/ polyuria and HYPONATREMIA. what normalizes this ?
FLUID RESTRICTION Normalizes the situation
Many cell fxs are very Sensitive to Changes in ECF K+ concentraions, therfore ECF K+ conc. normally is regulated precisely at about??
4.3 mEq/L
An Increase in Plasma K+ concentration of only 3-4 mEq/L can cause: ______
=>Higher concentration can lead to??
Cardiac Arrhythmias
=> higher concentration can lead to Cardiac Arrest of Fibrillation
What % of Total body K+ is concentrated IC and ECF?
IC= 98%
ECF= 2%
Increase intake of K effects ECF, somust get rid of it or more it into the IC
1. High plasma K+ concentration=
2. Low plasma K+ concentration=
1. High plasma K+ concentration= HYPERKALEMIA
2. Low plasma K+ concentration= HYPOKALEMIA
Factors that Shift K+ into Cells ( Decrease ECF K+) (from EC to IC) & could possible cause HYPOKALEMIA? 4
1. Insulin (VERY Powerful stimulant moving K into cell_
2.Aldosterone
3. B-Adrenergic stimulation (nerves SNS- NE or Epi)
4.Alkalosis
Factors that Shiftr K out of Cells (Increase EC K) From IC to EC..Could cause HYPERKALEMIA): 7
1. Insulin Deficiency (Diabetes Mellitus)
2. Aldosterone Deficiency (Addison's Ds-whole adrenal cortex can't produce hormones)
3. B-Adrenergic Blockade-(hypertensive meds prevent movement into cell actually move it out)
4.Acidosis
5. Cell Lysis (m. injury rbc lysed= releases K from cells)
6. Strenuous Exercise -(m. exercise=v of K to blood)
7. Increased ECF Osmolarity - ( from cells IC to EC to dilute Osm in EC causes ^ K w/in cells cause it to move out into EC)
Is aldosterone very important in regulation of K?
Na?
MAJOR player./ regulator in K+
- minor role in NA (AVP/ADH major hormone that regulates na conc in plasma)
Normal Tubular Handling of K+
1. K is reabsorbed 1' in ___ & also in ___
2.About _8_% of filtered load is deliverd to ___
3.Secretion of K into the ____ & ____ adds to the amt delivered; therefor the daily excretion is about __ % of K filtered at the glomerular capillaries.
Normal Tubular Handling of K+
1. K is reabsorbed 1' in _PCT _& also in _THICK ASC LoH_
2.About _8_% of filtered load is delivered to _DISTAL TUBULES_
3.Secretion of K into the _LATE DISTAL TUBULES_ & _COLLECTING DUCTS_ adds to the amt delivered; therefor the daily excretion is about _12_ % of K filtered at the glomerular capillaries.
Controls of Cortical Collecting Tubule (Principal Cells) K+ Secretion:
What are the 4?
1. Aldosterone
2. Extracellular K
3. Soduym volume delivery
4. acid-base status
Controls of Cortical Collecting Tubule (Principal Cells) K+ Secretion:
1. Aldosterone:
2. Increase EC K:
3. Increase Na (vol.) Delivery:
4. Acid-base Status
a. Acidosis:
b. Alkalosis:
1. Aldosterone: INCREASES K Secretion
2. Increase EC K: INcrease K Secretion (eat 5 bananas/oj)
3. Increase Na (vol.) Delivery: INcreases K Secretion (^ flow rate in distal renal tubule - bc allows more k to be secreted)
4. Acid-base Status
a. Acidosis: DECREASES K Secretion= HYPERKalemia development
b. Alkalosis: INCREASES K Secretion= HYPOKalemia development
The Effect of Aldosterone on K Excretion:
As Plasma Aldosterone INcreases = what happpens to Urinary K+ excretion?
It INCREASES
Mech of K+ Secretion & Na+ Reabsorption by Principal Cells of the Late Distal & Collecting Tubules.
1. Uptake from the Interstium into the cell by _______ in the _______ cell membrane
2._____ Diffusion of K+ from the ___ of the cell into the ____.
1. Uptake from the Interstium into the cell by _Na-K ATPase Pump_ in the _BASOLATERAL_ cell membrane
2._PASSIVE_ Diffusion of K+ from the _INTERIOR_ of the cell into the _TUBULAR FLUID_.
Mech of K+ Secretion & Na+ Reabsorption by Principal Cells of the Late Distal & Collecting Tubules.
DETERMINANTS of SECRETION: 3- which one is key?
1. Na-K Atpase Activity: ALDOSTERONE (<= KEY)
2.Electrochemical gradient for K Secretion fro mthe Blood to the Tubular Lumen
3.K Permeability of the Luminal Membrane
Intercalated Cells can _____ During K Depletion via?
Intercalated Cells can _REABSORB K+_ during K Depletion via: Cortical collecting ducts: ANTIPORT
H+ => out to lumen
K+ =>into cell
What are 2 blockades of Aldosterone effects in the role of Aldosterone in K+ metabolism?
1. Addison's ds- Reduced aldosterone secretion
2. K+-Sparing Diuretics: Spironolactone Acts on IC receptors & can't secrete K & can't absorb Na.
What is the Effect of Changes in K+ intake on Plasma K+ after Blocking Aldosterone System..
=>IF Aldosterone System is Blocked= As INcrease intake of mEq/day of K+, what happens to Plasma K concentration?
If Aldosterone System is Blocked: As INcrease Intake mEq/day of K+, PLASMA K+ CONCENTRATION INCREASES!!!!!!
Aldosterone secretion enhances Na Reabsorbtion & promotes K+ secretion..
1.How is Hypokalemia avoided when Na+ intake is reduced?
Decreased Na intake causes an INcrease in Aldosterone which Increases K secretion in cortical collecting ducts and this is how it advoids hypokalemia bc ther is no change in K excretion
Aldosterone secretion enhances Na Reabsorbtion & promotes K+ secretion..
2. How is hyperkalemia avoided when Na intake is enhanced?
Increase Na intake causes a Decrease in Aldosterone which has a neg. feedback and stops/slows K secretion in cortical collecting ducts (keeps it low w/in tubular) and that causes unchanged K excretion which avoids hyperkalemia
Effect of Distal Tubule Flow Rate on K+ Secretion.
1. HIgh flow rate= what for K secretion
1. High flow rate = allows more K to be secreted bc more flowed out
Effect of Distal Tubule Flow Rate on K+ Secretion.
2. Lower flow rate = what k secretion?
2. Lower flow rate= Less K secretion will occur bc as tubular flow rate is decretased, maintains what k secretin is in lumen and blocks further secretion
What are 5 causes of Hyperkalemia?
1. Renal Failure (endstages can't concentrate/dilute urine)
2. Decreased distal nephron flow (Heart failure, severe volume depletion, NSAIDS, etc)
3.Decreased Aldosterone or Decreased effect of Aldosterone
a. Adrenal insufficiency
b.Resistance to aldosterone (receptor defect)
c. K+ sparing diuretics (spironolactone)
4.Metabolic Acidosis (hyperkalemia is mild)
5.Diabetes (kidney disase, acidosis, Decreased insulin- esp. type 1)
What are 6 Causes of Hypokalemia (m. weakness,dizziness, some arrythemias)?
1. Very low intake of K+
2. GI loss of K+-diarrhea (aldosterone affects colon was well)
3. Metabolic Alkalosis
4.Excess insulin (drive more k into cell)
5.Increased Distal Tubular Flow (flushing too much out)
a.Salt wasting nephropathies
b. Osmotic Diuretics
c. loop Directs
d.Thiazide Diuretecs
6.Excess Aldosterone or other mineralocorticoids (caused by Khrons ds= tumor)
Hypokalemic manifestation:
1. Cardiovascular:
2.Vascular:
3.Muscular:
4.Neurological
5.Renal:
6. GI:
7. Metabolic:
Hypokalemic manifestation:
1. Cardiovascular: Arrythmias, tachcardias,impaired delayed contraction
2.Vascular: impaired pressor response to catecholamines angiotensin
3.Muscular: weakness, paralysis, respiratory failure, myalgias, cramps
4.Neurological: Confusion, depression
5.Renal: Nephrogenic D.I. (Polyuria), nreduced glomerular filtration, renal damgage, acidfication defects of urine
6. GI: Decreased bowel motiltity, ileus, constipation, nausea, vomiting, anorexia
7. Metabolic: Decreassed protein synthesis, metabolic alkalosis
Major place that Ca++ is controlled/regulated/ produced?
Body Ca++ homeostasis control is regulated byPTH produced by parathyroid glands.
PTH is major regulator of Ca++ balance
Decreased EC Concentraion of Ca++, causes PTH to work on what 3 places?
1.BONE-to enhance osteoclastic cells to eat up/relase into blood
2.GI TRACT- kidney converts nonactive from of Vit D3 to active from to the GI tract and INCREASE REabsorption of CA from the Gut/GI Tract (INcrease Serum Ca++)
3. KIDNEY- Increase reabsorption in Kidney of Ca++ & promotes Ca++ urine output
1. Ca is both ____ & ___ in Kidneys but NOT _____.
2. How much of Plasma Ca++ is filterable?
1. Ca is both _FILTERED_ & _REABSORBED_ in Kidneys but NOT _SECRETED_.
2. 60%(50%) of PLASMA Ca is filterable
The % of the filtered load of Ca++ remaining in tubular fluid as it flows down the nephron:
1. PCT=
2.Thick Asc. LOH-
3. DCT=
4. Collecting Duct=
5. Urine=
1. PCT= 40% (most in this)
2.Thick Asc. LOH- 30% (from + charge in lumen aids in flow??)
3. DCT= 10%
4. Collecting Duct= 5%
5. Urine=.5- 2%
Mech of Ca++ reabsorption in different segments of nephron:
1.PTC=
2. Thick Asc. LoH=
3.DCT/CNT=
1.PTC= (50-60%) PASSIVE PARACELLULAR
2. Thick Asc. LoH= (15%) PASSIVE PARACELLULAR
3.DCT/CNT=(10-15%) TRANSCELLULAR
Factors that Alter Renal Ca Excretion:
The following Increase/Decrease to cause a Decrease in Ca++ Excretion
1.___ BP
2. ____ ECFV
3. _____ Plasma Phosphate
4.____ PTH
5.Metabolic ____
6. ________
1._DECREASE_ BP (absorb more)
2. _DECREASE_ ECFV
3. _INCREASE_ Plasma Phosphate
4._INCREASE_ PTH
5.Metabolic _ACIDOSIS_
6. _VITAMIN D3_
Factors that Alter Renal Ca Excretion:
The following Increase/Decrease to cause an INCREASE Ca++ Excretion
1.___ BP
2. ____ ECFV
3. _____ Plasma Phosphate
4.____ PTH
5.Metabolic ____
1._INCREASE_ BP (absorb less)
2. _INCREASE_ ECFV
3. _DECREASE_ Plasma Phosphate (absorb less excrete more)
4._DECREASE_ PTH
5.Metabolic _ALKALOSIS_
The ___ normally reabsorbs 75-80% of the filtered phosphate through the ______ pathway
The _PCT_ normally reabsorbs 75-80% of the filtered phosphate through the _TRANSCELLULAR_ pathway
1.The DCT _____ about 10% of filtered load of phosphate
2.Approx 10% of the filtered phosphate is _____ in the ____.
1.The DCT _REABSORBS_ about 10% of filtered load of phosphate
2.Approx 10% of the filtered phosphate is _EXCRETED_ in the _URINE_.
1. Tm determines plasma phosphate concentration: ____ & ____ regulate Tm
2. Increasing Tm Increase P(phos), Thus the ______ Regulates P(phos)
1. Tm determines plasma phosphate concentration: _DIETRAY PHOSPHATE_ & _PTH_ Regulate Tm.
2. Increasing Tm Increase P(phos), Thus the _KIDNEY_ Regulates P(phos)
What is REnal Phosphate excretion by the kidneys controlled 1' by?
OVERFLOW MECHANISM
1. What is Transport Maximum (Tm) for Reabsorbing phosphate about?
2. When less than Tm of phosphate is present in glomerular filtrate, essentially _ALL_ the Filtered phosphate is ______.
3. When more than this is present, the EXCESS is ______.
1. (Tm) = 0.1mM/min
2. When less than Tm of phosphate is present in glomerular filtrate, essentially _ALL_ the Filtered phosphate is _REABSORBED_.
3. When more than this is present, the EXCESS is _EXCRETED_.
1.What hormone regulates phosphate reabsorption?
2. ____ promotes bone resorption, thereby dumping lg amounts of ______ into the ECF from the bone salts.
1. PTH Rregulates Phosphate Reabsorption
2. _PTH_ promotes bone resorption, thereby dumping lg amounts of _PHOSPHATE IONS_ into the ECF from the bone salts.
PTH decreases the Tm for phosphate by the:
RENAL TUBULES, so a greater proportion of the tubular phosphate is lost in the urine.
Magnesium Balance
1. MG++ %
A. Bone= __%
B. Cells= __%
C.ECF= __%
2.Plasma MG levels Regulated by:
1. MG++ %
A. Bone= _60_%
B. Cells= _39_%
C.ECF= _1_%
2.Plasma Mg++ levels Regulated by: KIDNEY
Magnesium Balance
3.Low levels of Mg Cause? (same for ca)
4. High Levels of MG have what effect?
3.Low levels of Mg Cause:
=>CNS & Neuromuscular Hyperactivity-reabsorption Increased (same for ca+)
4. High Levels of MG have:
=>Sedated Effect & Associated w/ Cardiac Arrest-Rapidly Excreted (lathergic)
Because acid concentration in the body is much LOWER than Na+, it is critical to keep it regulated since there is such a decrease of concentration comparativiely. What is Acid used for in the body that it is vital to keep thiese processes giong so must tightly regulate Body (H+) ? 4
1. Enzyme Systems
2. Blood cloting processes
3. Muscle contractions
4. Channels
(H+) (acid) concentration is so low in the body bthat it is expressed as pH.
1. What is the normal pH of Arterial Blood?
2. Venous blood and ISF?
1. Arterial Blood= 7.4
2. Venous Blood & ISF= 7.35
What is the pH range that is compatiable with life and once we get out of this range we won't make it/die?
pH=~6.8 to 7.8 (several hours)
Why is precise H+ regulation essential?
Bc the activities of almost ALL ENZYME SYSTEMS in the BODY are Influenced by H+ Concentration
What is the normal average concentration of H+ in the ECF (blood) is mEq/L?
.000004 mEq/L (40nEq/L) = very very very low
ECF
=>Normal pH=
=>Acidosis pH=
(plasma pH=)
=>Alkalosis pH=
(plasma pH=)
=>Normal pH=7.4 (arterial) (7.35 venous/ISF)
=>Acidosis pH= < 7.4
(plasma pH < 7.35)
=>Alkalosis pH= > 7.4
(plasma pH >7.45)
=>ICF pH=
=>Urine pH=
=>Gastric pH=
=>ICF pH= 6.0 - 7.4
=>Urine pH=4.5-8.0
=>Gastric pH=0.8 (biggest source of H+ concentraion & secretion)
Why is plasma (H+) so tightly regulated?
4ish?
1. (to not get out of acid base balance)
2.B/c Hydrogen ions are small & highly reactive
3. Bind to negative charges on proteins
4. Denature & inactivate enzymes (if too acidic)
How is (H+) in body fluids regulated (buffers)? 3
1. "Instaneous" -
2."Fast"-
3. "Slow"-
1. "Instaneous" -Chemical Acid-base buffer systems (body fluids) (blunt any change instaneoulsy)
2."Fast"- Respiratory System = regulates the removal of CO2 (expires Co2 to get rid of increased acidicity quickly) seconds to mins (max in hours)
3. "Slow"- Kidneys= excrete an acidic or alkaline urine (hours to days max in days) - (takes longer)
-ALL: just blunt system to get back in balance ( which kidney mostly does that part)
Bronsted-lowry def. of:
1.Acid=
2. Base=
3.Ioniation of an Acid=
a. Acid <=>
b. HA <=>
4.Conjugated Acid-Base Pair= 2 forms of _____
a.HA= _____ =
b. A- = _____=
1.Acid= Proton Donor
2. Base= Proton Accepter
3.Ioniation of an Acid=
a. Acid <=> (H+) + Base
b. HA <=> (H+) + (A-)
4.Conjugated Acid-Base Pair= 2 forms of _BUFFERS_
a.HA= _CONJUGATE ACID FORM_ =Proton Donor
b. A- = _CONJUGATE BASE FORM_= Proton Acceptor
Why when adding acid to a buffer soln. there is only a minimal pH change>?
Bc it is quickly converted to its conjugated from.
There are 2 kinds of acids:
1. Volatile Acid=
2. NonVolatile Acid=
1. Volatile Acid= potential acid= change quickly. (CO2)
=>Hyperventalte= too much acidity blow it off
=>hypoventilate= Not enough acid
2. NonVolatile Acid= Fixed Acid
=>Noncarboinic acid
=> must be buffered in kidneys mainly through urine
What happens when a strong acid such as HCl is added to water?
Completly dissociates into H+ and Cl-
What happens when a weak acid (HA) is added to water?
Only partially dissociates into H+ and A- and is LESS likely to release H+
(Some retain in acid form and others retain in base form)
What are ideal buffers & why?
WEAK ACIDS are ideal buffers bc have a range of physiological pH.. Bc more acid added to the conjucated form allows it to RESIST pH CHANGE
pK
K=
K=
K= Products/ reactants... = [ (H+)(A-)] / (HA)
k= Ratio of movement of products forward and reverse order of acids to disocaioate and form.
1.Apparent equilibruium constant K=
2. pK=
3. pK of an acid is what?(ph)/What makes up the total concentration of buffer systems?
1. Apparent Equilibrium constant K = TEMP. & Sol. Composition.
2.pK= (- Log K) = (+ log (1/K))
3. pK of an Acid is the pH at which 50% is HA & 50% is A- make up the total concentration of Buffer System.
The pH of the system is same as the ___ when each of the components (HCO3- & CO2) constitutes ______% of the total concentration of the _____ System.
The pH of the system is same as the _pK_ when each of the components (HCO3- & CO2) constitutes _50_% of the total concentration of the _BUFFER_ System.
Where is the buffer system most effective? & What does that mean?
Buffer System most effective: in the CENTRAL Part of the Curve where the __pH is NEARhe pK of the the system__.
=>This means that the change in pH for any given amt of acid or base added to system is smallest
=> (resutls in very small cahnge in pH)
When does the buffering system have no more bufffering power>?
change ph??
When all the CO2 has been converted to HCO3-
OR
WHen all HCO3- has been converted into CO2.
=>REsults in a biffer change in pH (at sigmoid protion)
The Capacity of a Buffer is Related to its: 2
1. pK relative to the pH of the solution
2.Concentration of the buffer
Henderson Hasselbalch equation tells us that ph=
pH= pK + log (base/acid)
What is the strongest, most effective buffer, and most important buffer in the body?
Bicarbonate (HCO3-)
1. Metabolic Component=
2. Respiratory Component=
1. Metabolic Component= Bicarbonate (HCO3-) (from metabolism)
2. Respiratory Component= PaCO2 (Pp vonverted to concentrion- sol. coef.)
1. Solubility of CO2 in H2O (ECF) @ 37c=
2.Pco2 in arterial blood=
3.(CO2)=
1. Solubility of CO2 in H2O (ECF) @ 37c= .03 mmol/L/mmHg
2.Pco2 in arterial blood= 40 mmHg(normal)
3.(CO2)= .03 x 40 = 1.2mmol/L
INCREASE Solubility Coefficient in mmol/L/mmHg
What is the normal pK of bicarbonate?
6.1
What is the bormal bicarbonare concentraion in blood?
24
what is the normal CO2 Concentration in blood?
1.2 mml/L/mmHg
What is Acidosis?
How is it effected by HCO3- & Pco2?
Acidosis= pH <7.4 (7.35)
=>Decrease HCO3-
=>Increase P(CO2)
What is Alkalosis?
How is it effected by HCO3- & Pco2?
Alkalosis= pH > 7.4 (7.45)
=> Increased HCO3-
=>Decreased P(CO2)
Buffers:
1. How is acid base balance regulation in the body achieved?
2.Acid-Base Conjugate pair can?
3.Body buffers: 2
1.Acid base balance regulation in the body achieved: Via WEAK ACIDS & BASES
2.Acid-Base Conjugate pair can: RESISTS CHANGES in pH (Buffer against change in (H+))
3.Body buffers:
1.BICARBONATE= most important
2. Non-bicarbonate-phospates , Hb, Pp(plasma protein)
The 3 non-bicarbonate buffers are?
1. Hemoglobin
2. Plasma Proteins
3. Phosphates
Non-Bicarb Buffer: HEMOGLOBIN (Hb):
1. Accounts for what % of nonbicarb buffering power of ECF?
2. Where does buffering capacity come from?
1. Hb= 80% of nonbicarb buff (RBC membrane highly permeable)
2.Buff cap comes almost entirely from the side group of AA: HISTIDINE (36/574 residues)
Non-Bicarb Buffer: HEMOGLOBIN (Hb):
3.Average pK of histidine side chain:
4.Hb is converted to _____ (pK= __) in tissue?
5.why is 4 answer important?
3.Average pK of histidine side chain: =~6.5
4.Hb is converted to _DEOXYHB_ (pK= _7.9_) in tissue
5. DeoxyHb better buffer for H+ in RBC generated by CO2 diffusion from tissues..
IMPORTANT BC: good buffer when CO2 enters from tissue to rbc=> converted to C.A.
Co2 + H2O Bicarb & C.A. takes place in RBC
Non-Bicarb Buffer: Plasma Proteins (PP)
1. Total buffering capacity of all PP=
2.Most abundant =
3.Buffering is also mediated through ___ ___ & ___ ___ of PP.
1. Total buffering capacity of all PP= 20% that of Hb
2.Most abundant = Albumin (contains 16 histidine residues -same as Hb)
3.Buffering is also mediated through _FREE AMINO_ & _CARBOXYL ENDS_ of PP.
Non-Bicarb Buffer: Phosphate Buffers
1.Important bc can do what w/ what kind of acids?
2.pK=
3. Phosphate buffer (ECF) is:
4.Buffering power =
1.IMPORTANCE: Fixed Acids (nonvolatile acids) which cna be removed/excreted in the urine.
2.pK= ~6.8 (better than pK of HCO3-
3. Phosphate buffer (ECF) is: LOW
4.Buffering power = Only a few% that of Hb
Under normal conditions the most important buffer system in the body is?? (in ECF)
BICARBONANTE BUFFER SYSTEM
WHy is Bicarbonate the best buffer?2
1. High concentration in ECF
2. Dual Regulation: Physiologically regulated by the: LUNGS & KIDNEYS
(Most others are regulated by kidneys and not the lungs, ex: phosphate can only be regulated by kidneys)
CO2 + H2O <=(c.a)=> H2CO3 <=> (H+) + (HCO3-)

1. If Exogenous Nonvolatile Acid is added (or base lost from body) what happens to equilibrium?
SHIFTS TO THE LEFT = creates more Carbonic acid
CO2 + H2O <=(c.a)=> H2CO3 <=> (H+) + (HCO3-)

1. If Exogenous Nonvolatile BASE is added what happens to equilibrium?
SHIFTS Equilibrium to the RIGHT
What does carbonic anhydrase do?
Speeds up the reaction between CO2 and H2O. to form H2CO3 to be further broken down into H+ + HCO3-
IN what cells is Carbonic Anhydrase found in? 4
1. RBCs
2. Gastic Acid-Secreting Cells
3. Renal Tubular Cells
4. Walls of the lung alveoli
A decrease in HCO3- will ___ CO2 levels causing ___ Acidity, so will :
A decrease in HCO3- will _INCREASE_ CO2 levels causing _MORE_ Acidity, so will : BLOW OFF MORE CO2 IN THE LUNGS to balance acid-base
pH "Normalizers"= _______
- is pH ever normalized???
Compensations-Virtually NEVER terturns the pH to Normal.. just comes back towards normal.
1. Respiratory
2. Metabolic
pH "Normalizers"=
Compensations- which is fast slow?
1. Respiratory=
2. Metabolic=
1. Respiratory= FAST
2. Metabolic= SLOW
How do kidneys regulate (H+)?
By excreting an acidic or basic urine (pH 4.5 - 8.0)
How is urine pH determined?
By a net balance of HCO3- filtered to H+ secreted.
What 2 purposes does secreted (H+) serve?
1. REabsorbs filterd HCO3- (to balance out secretion of acid w/retention of HC)3- bc it resorbs 99%)
= 180L/d x 24 mEq/L = 4,320 mEq/d
2. REmove extra nonvolatile (fixed) acids fro mthe body (replenish HCO3- consumed by buffering) => Titratable acids (TA) & NH4+ (way to remove excess acids)
Bicarbonate Reabsorption %:
Bicarbonate Reabsorption %:
1.Proximal Tubule=
2. Thick Ascending LoH=
3.Distal Tubule & Collecting Duct=
Bicarbonate Reabsorption %:
1.Proximal Tubule= ~85%
2. Thick Ascending LoH= ~10%
3.Distal Tubule & Collecting Duct= >4.9%
4. How much of filtered HCO3- is reabsorbed (;PT, Thick Asc. LoH, DT/CD)?
5. Threshold?
4. 99.9%
5. Threshold @ 28 mEq/L
For each Bicarbonate 'renabsorbed' there must be how many H+ secreted?
1.... its a 1:1 relationship - to keep acid/base balance in check.
LOOK AT SLIDES 4,5,6, 9, 10,12 IN ACID-BASE BALLANCE 2 PPT
LOOK AT SLIDES 4,5,6, 9, 10,12 IN ACID-BASE BALLANCE 2 PPT
EAP (Endogenous Acid Production):
=> H+ produced therefore, bust have???
HCO3- consumed in ECF
Metabolism & the gut together add about ____ mmol H+ (____ ____ ____) per day to the body fluids from what??
Metabolism & the gut together add about _70-100_ mmol H+ (_ENDOGENOUS ACID PRODUCTION [EAP_) per day to the body fluids from:
1. DIET
2.GUT: CO2 + H20 => (HCO3-) + (H+)
(Gastric acid cells from pancreas secretions)
Acid Exretion= AKA = Bicarbonate Regenerated
1.When new HCO3- replaces HCo3- consumed during buffering of EAP =
'RENENERATED' ( regenerates/ makes new HCO3- lost inbuffering of EAP)
Acid Exretion= AKA = Bicarbonate Regenerated
2. When HCO3- replaces HCO3- lost during Filtration =
'REABSORBED' (same HCO3- just reasorbed)
Acid Exretion= AKA = Bicarbonate Regenerated
Regenerated (new) HCO3- and Resorbed HCO3 are quite similare except for???
HOW SECRETED H+ ARE DISPOSED OF.
What is quantitatively the MOST Important Urinary buffer?
AMMONIUM (NH4+)
Glutamine is produced 1' in the _____ & transported to the ___ => ___ where it is metabolized into???
Glutamine is produced 1' in the _LIVER_ & transported to the _BLOOD_ => _PT_ where it is metabolized into:
=> 2NH+ Compounds & 2 HCO3- Compounds
=> ( 2NH4+) + (A-) = (2HCO3-)
NH4+ Handling in the Tubule:
1.Secreted into lumen by:
2.Reabsorbed by ___ & Accumlates in the ___ ___: NH4+ <=> ___
1.Secreted into lumen by: PT
2.Reabsorbed by _TAL_ & Accumlates in the _MEDULLARY ISF_:
NH4+ <=> _(H+) + NH3_
NH4+ Handling in the Tubule:
3. NH3 can diffuse into the lumen of: ___
4.What happens in there?
3. NH3 can diffuse into the lumen of: _CD_
4. DIFFUSION -TRAPPING in the Lumen of the CD:
NH3 + (H+) => NH4+ is excreted.
H+ Excreted as NH4+:
Rate of Excretion deponds on what 3 things?
1. Rate of synthesis & Secretion of NH4+
2. pH of Tubular Fluid
3. Rate of Urine Flow
Rate of Exretion of H+ as NH4+ Depends on 3:
1. Rate of Synthesis (in PT) & Secretion of NH4+. Which depends on what activity?
Glutaminase activity ( increase chronic acidosis)
Rate of Exretion of H+ as NH4+ Depends on 3:
2. pH of Tubular fluid:
=> The Lower the pH (MORE ACIDIC), what happens with acid/ NH3/NH4?
=>The Lower the pH(MORE ACIDIC), the More NH3 can Diffuse into the Lumen ( into the CD which converts NH3 +H concentrated in the intracalted cells to NH4 to be exreted)
Rate of Exretion of H+ as NH4+ Depends on 3:
3. Rate of Urine Flow
=> What does passive diffusion of NH3 into the lumen do if the rate of fluid increases?
Passive Diffusion of NH3 into the lumen INCREASES if the rate of Fluid Flow increased.
( The faster the flow rate= more excreted)
If there is a 1' change that occurs in (HCO3-) what kind of disorder results? ex?
METABOLIC ACID-BASE Disorder
ex: Hyperbicarbonatemia or Hypobicarbonatemia.
(metabolibic protion then metabolic disorder)
If there is a 1' change that occurs in P(CO2) then what is this disorder? ex?
RESPIRATORY ACID-BASE Disorder
ex: Hypercapnia or Hypocapnia
( pH low= Respiratory acidosis, pH high= Respioratory Alkalosis)
The 1' Acid Base Disorders:
Compared to normal- What does Respiratory Acidosis do in the following:
1.pH=
2. H+ =
3. Pco2=
4. HCO3 =
Respiratory Acidosis
1.pH= Decreases
2. H+ = Increases
3. Pco2= Increases (a lot)
4. HCO3 =Increases
The 1' Acid Base Disorders:
Compared to normal- What does Respiratory Alkalosis do in the following:
1.pH=
2. H+ =
3. Pco2=
4. HCO3 =
Respiratory Alkalosis
1.pH= Increase
2. H+ =Decrease
3. Pco2= Decrease (a lot)
4. HCO3 =Decrease
(Everything opposite of Respiratory Acidosis)
The 1' Acid Base Disorders:
Compared to normal- What does Metabolic Acidosis do in the following:
1.pH=
2. H+ =
3. Pco2=
4. HCO3 =
Metabolic Acidosis
1.pH= Decrease
2. H+ = Increase
3. Pco2= Decrease
4. HCO3 = Decrease (a lot)
The 1' Acid Base Disorders:
Compared to normal- What does Metabolic Alkalosis do in the following:
1.pH=
2. H+ =
3. Pco2=
4. HCO3 =
Metabolic Alkalosis
1.pH= Increase
2. H+ = Decrease
3. Pco2= Incease
4. HCO3 = Increase (a lot)
Metabolic Acidosis:
1. Plasma pH ______ due to: __
2. Defense Mechansisms
a.
b.
c. Compensation:
Metabolic Acidosis:
1. Plasma pH _DECREASE_ due to: _DECREASE IN HCO3- PLASMA (1' alteration)
2. Defense Mechansisms
a. ICF Buffering
b. ECF Buffering
c. Compensation: DECREASE Pco2 = Blow off more CO2 until can get more bicar to neutralize
Metabolic Acidosis Ex:
1. Addition of Acid= 4
a. Diabetic Ketoacidosis (elevated B-Hydroybutyrix acid acetoacetic acid) - Diabetics t dont have enough insulin to convert fats to ketoacids & accumulate in body= become acidic)
2. Starvation Ketosis (elevated B-Hydroxybutyric acid)
3. Severe Exercise or Hypoxemia (lactic Acid)
4.NH4CL Adminsatration
Metabolic Acidosis Ex:
2. Loss of Base:2
1. Certain renal diseases
2. G.I. disturbances ( Aspirations or Diarrhea) - lose a lot of bicarbs = metabolic acidosis.
What measures the extent/severeity of Metabolic Acidosis?
Anion Gap=
Na - (HCO3 + Cl)
Normal= 6-14 (12)
((+) #s comes from this equation having more cations than anions. Much of the "missing anion"=Albumin)
To maintain electrical neutrality, the serum contains:
Equal concentrations of Anions and Cations
Serum NA accounts for most of the Cations in the Serum Anion gap (along with Ca, Mg, K)= 140. & Serum HCO3 &Cl caccount for ~128 of balancing anions.
=> The REmaninan anions (~12mEq/L) include:
Negatively charged proteins, phosphates, & sulfates.
The difference between the measured HCO3- & Cl- & the measure Na+ =
SERUM ANION GAP
The clinical significanve of the anion gap:
An Elevation in the anion gap almost always indicates??
The presence of a gap metabolic acidosis, although some other processes can change the anion gap. In the presence of these other disorders, the assessment of gap metabolic acidosis can be clouded.
If someone has an anion gap that is greater than 14=
SEVERE ACIDOSIS= seen w/ diabetics
Metabolic Acidosis= increased Anion Gap
=> INcreases Acid Production bc?4
1. Lactic Acidosi
2. Starvation Ketoacidosis
3. Alcoholic Ketoacidosis
4. Diabetic Ketoacidosis
( Not part of anion gap, extra anions, so addional play a role to Increase gap)
Metabolic Acidos= Normal Anion gap:
Bc of: GI Loss of Bicarbonate- due to 4 things?
1. Diarrhea- not big change in anion gap bc replace lost bicarb with cl-
2. Small Bowel or Pancreatic Drainage
3. Obstructed Ileal Loop
4. Anion Exchange Resins
Impact of Metabolic Acidosis on Bone- See ACID/BASE 2 Ppt- slide 23
Impact of Metabolic Acidosis on Bone- See ACID/BASE 2 Ppt- slide 23
Some Dental Effects of Chronic Metablic Acidosis:
1. Rate of Dentin Formation: __
2.Persistent Prozimal Renal Tubular Acidosis=> __ __, esp. in young pts.
3. Fluoride metabolism:
a. Absorption: __
b. Renal Clearance of Fluoride: ____
c. Conc. of Fl & Mg in bone & enamel : __
4. Sheeding & Erruption: __
5. Permanent teeth: __; __ Tooth Development.
1. Rate of Dentin Formation: SLOWS DOWN_
2.Persistent ProXimal Renal Tubular Acidosis=> _ENAMEL HYPOPLASIA_, esp. in young pts.
3. Fluoride metabolism:
a. Absorption: _ Dependent on GASTRIC Content pH_
b. Renal Clearance of Fluoride: _REDUCED_
c. Conc. of Fl & Mg in bone & enamel : _HIGH_
4. Sheeding & Erruption: _DELAYED_
5. Permanent teeth: _AGENESIS_; _RETARDED_ Tooth Development.
Metabolic Alkalosis:
1. Plasma pH ____ , due to ___
2. Defense Mechanisms:
a.
b.
C. Compensation:
1. Plasma pH _INCREASE_ , due to _an INCREASE in HCO3- in plasma ( 1' alteration)_
2. Defense Mechanisms:
a. ICF Buffering
b.ECF Buffering
C. Compensation: INCREASE Pco2 (hypoventilation, retain more CO2 to facilitate this bc normally associated with hyperventilation ???????)
Examples of Metabolic Alkalosis:
1. Ingestion of Antacids (bc of gerds)= example of::
2. Gastric vomiting or Gastirc Aspirations is ex. of???
1. Addition of Base
2.Loss of Acids=== THIS IS USUALLY WHAT CAUSES ALKALOSIS
Dental Effects of Chronic Alkalosis:
1. __ Caries resistance (both metabolic & respiratory)
2. ____ Rate of Fl excretion by kidney=> __ Fl levels in both Soft & hard tissues.. ( bc of ___ Clearance of Fl)
3.Chronic Respiratory Alkalosis ( living 5500m above sea level)=> Disturbance in the _____ of the ____ ___.
Dental Effects of Chronic Alkalosis:
1. _INCREASED_ Caries resistance (both metabolic & respiratory)
2. _INCREASED_ Rate of Fl excretion by kidney=> _REDUCED_ Fl levels in both Soft & hard tissues.. ( bc of _INCREASED_ Clearance of Fl)
3.Chronic Respiratory Alkalosis ( living 5500m above sea level)=> Disturbance in the _MINERALIZATION_ of the _INCISOR ENAMEL_.
Respiratory Acidosis:
1. Plasma pH __ due to ___ .
a. __ of Respiratory Centers (__)
b.___Air flow (ex:__,__)
c.__ in Respiratory M. (__ __)
Respiratory Acidosis:
1. Plasma pH _DECREASES_ due to _an INCREASE in Pco2 (1' alteration) (Deep hypoventilation)__ .
a. _DEPRESSION_ of Respiratory Centers (_BARBITURATES_)
b._REDUCED_Air flow (ex:_ASTHMA_,_EMPHYSEMA_) (lungs themselves)
c._DEFECTS_ in Respiratory M. (Muscular Dystrophy_) (Paralyis, alter ability to Increase Resp. = INcrease accumulation of CO2.
Respiratory Acidosis:
2. Defense Mechanisms:
a.
b.Compensation:
Respiratory Acidosis:
2. Defense Mechanisms:
a. ICF Buffering (note that in respiratory disorders defense mechs only ICF bufferering, no ECF buffering.)
b.Compensation: INCREASE Net REnal H+ Excretion (to Increase HCO3- plasma) (excretemore bicarb->Increase renal H+ acid).
Respiratory Alkalosis:
1. Plasma pH __ Due to __
a.__ of Resp. System ( __, __ __)
b. __ of peripheral chemoreceptors (__)
c. __ adjusted resiratory pump ( __ too __)
Respiratory Alkalosis:
1. Plasma pH _INCREASES_ Due to _DECREASE in Pco2 ( 1' alteration)_
a._STIMULATION_ of Resp. System ( _EMOTIONAL (axiteny)_, _SALICYLATE POSIONING (asprin OD)_)
b. _STIMULATION_ of peripheral chemoreceptors (_HYPOXEMIA_)
c. _INADEQUATELY_ adjusted resiratory pump (_Va_ too _HIGH_) (Too high= Respiring too much= decr. Pco2= resp. alkalosis.
Respiratory Alkalosis:
2. Defense Mechanism:
a.
b. Compensation:
Respiratory Alkalosis:
2. Defense Mechanisms:
a. ICF Buffering (note that in respiratory disorders defense mechs only ICF bufferering, no ECF buffering.)
b. Compensation: DECREASE Net Renal H+ Excretion ( which DECREASES (HCO3-) plasma)
What is probably the best compensated primary disturbance out of the 4 primary disturbances/ acid base balance?
RESPIRATORY ALKALOSIS
Compensation= Decrease Net Renal H+ excretion--> which Decreases HCO3- plamsa.
Analysis of Acid-Base Disorders:
1. First Examine the __
a.
b.
2. Second Determine if it is ____ or ____
a.
b.
Analysis of Acid-Base Disorders:
1. First Examine the _pH_
a. Possibility of ACIDOSIS if pH < 7.4
b. Possibilbity of ALKALOSIS if pH >7.4
2. Second Determine if it is _METABOLIC_ or _RESPIRATORY_
a. METABOLIC if the 1' Alteration is Bicarbonate (HCO3-)
b. RESPIRATORY if the 1' Alteration is Pco2
What is a substance that increases the rate of urine volume output, thus lowers blood volume and pressure?
DIURETETICS
What is the 1' effect of most diuretics?
In INCREASE Solute Excretion, Mainly as NaCl
What are 5 ds that may cause blood folume to Increase outside of narrowly defined limits and needs diuretics to decrease blood volume and pressure by increasing rate of urine vol out?
1. Hypertension
2. CHF
3. Liver Cirrhosis
4. Nephrotic Syndrome
5. Renal Failure
Osmotic Diuretics
1. Mechanism of Action:
2. Tubular Site of Action:
3. Ex of diuretic:
Osmotic Diuretics
1. Mechanism of Action: Inhibit Water & Solute Reabsorption by Increasing Osmolarity of Tubular fluid ( increase H2O loss bc not reabsorbed)
2. Tubular Site of Action: Proximal tubules (mainly)
3. Ex of diuretic: Mannitol
Loop Diuretics
1. Mechanism of Action:
2. Tubular Site of Action:
3. Ex of diuretic:
Loop Diuretics
1. Mechanism of Action: Inhibit Na-K-Cl transport in luminal membrane
2. Tubular Site of Action: Thick Ascending LoH
3. Ex of diuretic: Furosemide, Bumetanide
Thiazide Diuretics:
1. Mechanism of Action:
2. Tubular Site of Action:
3. Ex of diuretic:
Thiazide Diuretics
1. Mech of Action: Inhibit Na-Cl co-transport in luminal Membrane
2. Tubular Site of Action: Early Distal Tubules
3. Ex of diuretic: Hydrochlorthiazide, Clorthalidone
Carbonic Anhydrase Inhibitors:
1. Mechanism of Action:
2. Tubular Site of Action:
3. Ex of diuretic:
Carbonic Anhydrase Inhibitors:
1. Mech of Action: Inhibit H+ secretion & HCO3- Reabsorption , which Reduces Na+ Reabsorption.
2. Tubular Site of Action: Proximal Tubules
3. Ex of diuretic: Acetazolamide
Aldosterone Antagonists:
1. Mechanism of Action:
2. Tubular Site of Action:
3. Ex of diuretic:
Aldosterone Antagonists:
1. Mech of Action: Inhibit action of Aldosterone on Tubular Recepetors, Decrease Na+ Reabsorption, & Decrease K+ Secretion
2. Tubular Site of Action: Collecting Tubules
3. Ex of diuretic:Spironolactone, Eplerenone
Na+ Channel Blockers
1. Mechanism of Action:
2. Tubular Site of Action:
3. Ex of diuretic:
Na+ Channel blockers:
1. Mech of Action: Block entry of Na into Na Channels of Luminal Membrane, Decrease Na Reabsorption, & Decrease K+ secretion.
2. Tubular Site of Action: Collecting Tubules
3. Ex of diuretic: Triamterene, Amiloride)
Osmotic Diuretics:
1. No interaction e/ ___ Systems
2.All Activity depends on:
3. Where does it block Water reabsorption?
1. No interaction w/ _TRANSPORT_ Systems
2.All Activity depends on: OSMOTIC PRESSURE EXERTED in LUMEN
3. Blocks Water Reabsorbtion in:
a. Prozimal Tubule (mainly)
b. Descending Loop
c. Collecting Duct
Osmotic Diuretics:
4.Results in:
Large water loss , smaller electrolytle losss=> can result in HYPERNATREMIA
Osmotic Diuretics:
Ex: Injection into blood stream of substances that are not easily reabsorbed by renal tubules, such as 3
urea, mannitol, & succrose
Osmotic Diuretics
Ex: High blood glucose levels in diabetes mellitus pts=> the ___ in Tm of glucose => excess glucose in the ___ __ act as an OSMOTIC DIruetic => __ __ of fluid into the urine.
Ex: High blood glucose levels in diabetes mellitus pts=> the _INCREASE_ in Tm of glucose => excess glucose in the _TUBULAR FLUID_ act as an OSMOTIC DIruetic => _RAPID LOSS_ of fluid into the urine.
( pt w/diabetes= loss of glucose in tubules bc reach Tm=> carry out water as well so osmotic diuertics effects)
What are the most potent diuretics available?
Loop Diuretics
How do Loop Diuretics work/mech of action?
- ex:
=> Decrease active Na-Cl-K Reabsorption in the TAL.
=> Ex: Furosemide (Lasix), Ethacrynic Acid, & Bumetanide
People on Loop Diuretics can not?
Concentrate their urine
Most common use/uses for Loop Diuretics?
1. CONGESTIVE HEART FAILURE
2. Hypertension
What diureti inhibits Na-Cl reabsorption in the Early distal tubules?
Thiazide Diuretics
1. Thiazide Diuretics causes Increased __ Reabsorption, Decreasing __ excretion & ___ __.
2. So, major use(s) for them:
1. Thiazide Diuretics causes Increased _Ca++_ Reabsorption, Decreasing _Ca++_ excretion & _RENAL STONES_.
2. So, major use(s) for them:
1. HYPERTENSION
2. Renal Stones
Thiazide Diuretics are given to facilitate Ca++ bc??
Impair NaCl cotransport in Early DIsttal tubule.
- No Na+ can leave the celll- so ca+ can't enter cell, so Increase Ca+ reabsorption (on basolateral portion) & less ca in urine/
Thiazide Diuretics more Ca++ is reabsorbed due to the blockage of what where?
Blockage of NaCL Pump in early distal tubules.
Acetaxolamide inbits the enzyme ___ ____, which is critical for the reabsorption of bicarb in PT..
CARBOINIC ANHYDRASE
(Acetaxolamide is a Carbonic Anhydrase inhibitor)
What is the major renal effect of Carbonic anhydrase inhibitors?
Bicarbonate Diuresesi
What is the disadvantage of Carbonic Anyhydrase Inhibitors?
That they canuse some decree of METABOLIC ACIDOSIS due to the Excessive Loss of HCO3- in the urine.
What is the major application of C.A. Inhibitors?? any what does it do there?
In the treatment of Glaucoma where they reduce HCO3- Secretion into Aqueous Humor of the Eye Reducing Pressure.
(also used to treat metabolic alkalosis)
What does Carbonic Anhydrase mainly do?
Acts on distribution of Bicarbonate reabsorbtion.
What is the mechanism of CAInhibitors and what are they useful in?
=> Block CA catalysation of CO2/Carbonic Acid/Carbonate Equilibrium
=> Useful for treating Glaucoma *& metabolic Alkalosis, but can cause metabolic Acidosis from HCO3- depletion.
Spironolactone & Eplererone (ksparing/aldosterone antagonist diuretics) are ____ receptor ____ that compete with aldosterone for recpetor binding sites in the ___ __ __ __ __ .
Spironolactone & Eplererone (ksparing/aldosterone antagonist diuretics) are _MINERALOCORTICOID_ receptor _ANTAGONIST_ that compete with aldosterone for recpetor binding sites in the _CORTICAL COLLECTING TUBULE EPITHELIAL CELLS_ .
Triamterene and Amiloride (K sparing diuretics/ NaChannel Blocker Diuretics)
- __ the reabsorption of Na & Secretion of K in the cortical colleting tubules.
-Often used in combo with:
Triamterene and Amiloride (K sparing diuretics/ NaChannel Blocker Diuretics)
- _DECREASE_ the reabsorption of Na & Secretion of K in the cortical colleting tubules.
-Often used in combo with: THIAZIDE DIURETICS to RESTRICT K+ LOSS.
Aldosterone antagonists and Na+ Channel Blockrs both are K+ Sparring Diuretics, but act on diff areas?
1. Aldosterone Antagonists: Acts on INTERCELLULAR RECEPTORS of Collecting Tubules
2.Na+ Channel Blockers Act on Na Channel of collecting tubule.
Diabetes Insipidus= lack of response to ADH= highly water urine.
__ Water reabsorption, hypernatremia, & ___ Thrist.
_DECREASED_ Water reabsorption, hypernatremia, & _INCREASED_ Thrist.
Diabetes Insipidus:2 types:
1. Nephrogenic=
2. Central=
1. Nephrogenic= No Response to ADH = Can't reproduce- RECEPTOR DEFECT
2. Central= Lack of ADH- hypothalimic pitiutiary- secretion prob.= POST. PITIUTIATRY DEFECT.
What ds is characterized by Decreased Na+ Reabsorption & Decreased K+ Secretion; LACK OF ALDOSERONE= Adrenal Cortex Deficiency:
Addison's Disease
What syndrom is characterized as: Decreased Na, Ca, Hco3 reabsorption, hypotension, Decreased activity of Na-K-2Cl co-transporter in Thick Asc. LoH (genetic)... High vol. Watery Urine & Hypokalemia very possible
BARTTER's Syndrome
Gitleman's syndrome is a genetic defect that decreases what where?
Decreased NaCl reabsorption in Early DT.
= Blocked Cotransport of NaCl = passive movement of K which incrases k loss bc high flow rate.
Conn's Syndrom is 1' ___ excess.
Due to:
Conn's Syndrom is 1' _Aldosterone_ Excess. (aldosteronism )(promotes k secretion)
- due to: benigned tumor in adrenal cortex. ( zona glomerulous of adrenal gland)
Conn's Syndrom is an ex of Abnormal Tubular Fx that cause:
1. __ Na Reabsorption (DT&CT)
2. __ Na+ Excretion (__ State)
3. __K+ Secretion
4. __ Plasma K+
5. __ BP
1. _INCREASED_ Na Reabsorption (DT&CT)
2. _<=>_ Na+ Excretion (_STEADY_ State)
3. _INCREASED_K+ Secretion
4. _DECREASE_ Plasma K+
5. _INCREASE_ BP
Examples of Abnormal Tubular Fx= INCREASED REABSORPTION
6- syndromes/ds
1. Conn's Syndrome
2.Glucocorticoid Remediable Aldosteronism(GRA)
3.Pseudohyperaldosteronism: 11-HSD deficiency
4.Renin Secreting Tumor:
5.Inappropriate ADH Syndromes
6.Liddle's Syndrome.
Abnormal Tub. Fx= ^ Reasorb..
Glucocorticoid Remediable Aldosteronism(GRA)
What is it?
How is it remediated?
Eccess aldosterone secretion due to abnormal control of aldoseterone synthase by ACTH (Genetic).
=> ACTH no effect normally, but fused here, so when ^ACTH instead of cortical there is an Increase in Aldosterone production.
=> Remediate by admin cortisol to this person.
Cortisol therapy used to control.
Abnormal Tub. Fx= ^ Reasorb..
Psuedohyperaldosteronism: 11-HSD Deficiency
- what is it?
-what induces it?
Normally 11HSD converts cortiosol to corisone in adrenal gland, but here deficient, so corisol stiiumulats other mineralcorticosteroid recepetors.
=> Alters renal tubular exhange of Na (retained, K(excteted) & H (excreted).
=> Results: INcrease ECFV (Hypertension Edema) , Hypokalemia (weakness, m. spasms), & Metabolic ALkalosis.
Abnormal Tub. Fx= ^ Reasorb..
Renin Secreting tumor- is??
EXcess ang2 formation.
in kidneys screts IN crease renin= in crease ang 2= too much aldosterone.
Abnormal Tub. Fx= ^ Reasorb..
Inappropriate ADH Syndromes is??
Excess ADH or V2R activity. (opposite of diabetes)
=> Too much water retention in the blood associated with caronioma , ect.
Abnormal Tub. Fx= ^ Reasorb..
Liddle's Syndrom
- What is it?
-diuretic theray>
Excess Activity of Amiloride senstive Na channel (Genetic)
=> Enac channel retaining too much Na & H2O- so must give fluormide or orther diruretic to prevent retention of NA.
Abnormal Tub. Fx= ^ Reasorb..
Liddle's Syndrom: ( excess Na Channel activity in LATE DT & CD!) Does what?
1. __ Na+ reabsorption (DT&CT)
2.__ Na+ Excretion (__ state)
3. __ BP
4.__ Plasma Renin
5. __ Aldosterone
1._INCREASED_ Na+ reabsorption (DT&CT)
2._<=>_ Na+ Excretion (_STEADY_ state)
3. _INCREASED_ BP (B/c of water )
4._DECREASED_ Plasma Renin
5. _DECREASED_ Aldosterone
Liddle's syndrom is excess activity of amiloride senstive Na channels in cortical collecting tubules... what are the treatments.?
1. NA Channel Blockers:
a. Amiloride
b. Triamterene
2. Kidney transplant
Controls of Cortical Collecting Tubule (Principal Cells) Each does what w/ K+ Secretion:
1. Aldosterone: __ K+ Secretion
2. Extracellular (K+):__ K+ Secretion
3. Sodium (vol.) Delievery: __ K+ Secretion
4. Acid-Base Status
a. Acidosis: __ K+ Secretion
b. Alkalosis:__ K+ Secretion
1. Aldosterone: _iNCREASES_ K+ Secretion
2. Extracellular (K+):_INCREASES_ K+ Secretion
3. Sodium (vol.) Delievery: _INCREASES_ K+ Secretion
4. Acid-Base Status
a. Acidosis: _DECREASES_ K+ Secretion
b. Alkalosis:_INCREASES_ K+ Secretion
As we age there is a Increase in loss of nephrons... What happens to the nephrons we have left?
They get bigger and and increase in GFR
What is Renal Nephronitis?
Chronic inflammation of Nephrons
With renal disease what happens to nephrons?
adds to destruction of nephrons.
In Chronic Renal Disease, the surving nephrons enlarge
Can nephrons be regenerated?
NO! ONce they are lost they are gone!
After the loss of nephrons or a Nephronectomy what happens to the remaining kidney?
Kidney can hypertrophy (grow) after loss of nephrons...
After nephrectomy ,the remaining kidnyey gets larger (nephrons enlarge) to make up for loss of other kidney.
Total Renal Excretion in Renal Failure Compared to normal.
1. ___ # of nephrons
2. ___ Total GFR
3. ___ GFR per Nephron
4. ___ Urine Flow Rate
5. ___ Vol. Excreted per Nephron
Renal failure does this to the following in comparasion to normal renal fx
1. _DECREASE_ # of nephrons (from 2 mil to 500,000)
2. _DECREASE_ Total GFR ( from 125 to 40)
3. _INCREASE_ GFR per Nephron (from 62.5 to 80)
4. _SAME_ Urine Flow Rate
5. _INCREASE_ Vol. Excreted per Nephron (from .75 to3)
Chronic Kidney Disease (CKD)
1. ___ Americans (__ in __ US adults)- have CKD & __ moreare @ ^ risk.
2. ___ is the best estimate of Kidney fx.
3. Persisten ____ means CKD.
Chronic Kidney Disease (CKD)
1. _20 MIL__ Americans (_1_ in _9_ US adults)- have CKD & _20 MIL_ moreare @ ^ risk.
2. _GFR_ is the best estimate of Kidney fx.
3. Persistent_PROTEINURIA_ means CKD.
What are the 3 simple test that can detect CKD?
1. BP
2.Urine Albumin
3. Serum Creatinine -(can determine a fall in GFR (sm ^ in serum creatintine can have a lg decrease in GFR))
CKD is a vicious cycle.. As 1' Kidney disease=> 1.Increase loss of nephrons=> 2a,b=>3=>4 =>__
1' Kidney ds=>
1. Decrease Nephron # =>
2. (a) Hypertrophy& Vasodilation of surviving nephrons.
(b) Increased Arterial Pressure
==>
3.Incrased Glomular pressure &/or Increased Filtration. =>
4.Glomerular Sclerosis=>
5.(+) FB on Decrease Nephron #.

Increased loss of nephrons=> Leads to Increased End Renal Ds or kidney failure.
What is isothenuria?
Loss ability to concentrate or dilute urine
Renal Failure occurs when Loss of nephrons is more than??
75%
Up to 90% of Renal pts w/ CRD were found to have oral symptoms of _____
UREMIA
90% CRD pts have oral symptoms of Uremia:
20..
1. Enlarged (asymptomatic saalivary glands)
2.Decreased Salivary flow
3. Dry mouth
4. Odor of urea on breath
5. Metallic Taste
6. Increased Calculus Formation
7. Low Caries rate
8.Enamel Hypoplasia
9.Dark Brown stains on crowns
a. Extrinsic (2ndary to liquid ferrous sulfate therapy)
b. Intrinisc (2ndary to Tetracylcline staining
10. Dental malocclusions
11. Pale mucosa w/ diminished color dmarcation between attached gingiva & alveolar mucosa
12. Low-grade gingival inflammation
13. Petechiae & Ecchymosis
14.Bleeding from Gingiva
15. Prolonged Bleeding
16. Candidal Infections
17.. Burning & tenderness of mucosa
18.Erosive glossitis
19. Tooth Erosion (due to regurgitation associated w/dialysis)
20. Dehiscence wounds (splitting open wounds bleeding)
Etiology of Uremic Stomatitis??
Unknown, but suggested that it may be the consequence of Raised levels of Ammonia compound.
How is ammonia formed>
Through the action of bacterial ureases modifying salivary urea, which is elevated in affected pts (uremic stomatitis)
When does Uremic Stomatitis appear>
When blood urea levels are higher than 300 (normal is 18-21)
If urea increased =Urea posioing = secreted in ___ side of teeth.
Lingual side of teeth.
Ureases in saliva do what?
Break down urea into NH4 too much nh3 is responsible for uremic somatisis.
What are the adherent white patches on the ventral surface & lateral border of the tongue and the floor of the mouth?
UREMIC STOMATITIS
What are some ESRD that affect the oral cavity?
1. Renal Osteodystrophy- (RO)-in mandible and maxilla are bone demineralization, loss of trabeculation, gound glass appearance, total or partial loss of lamina dura, giant cellls or brown tumours may occur, jaw thins.
2. Enamel hypoplasia
1. The dimensions of renal clearance are
a. mg/mL
b. mg/min
c. ml plasma/min
d. ml urine/min
e. ml urine/ml Plasma
C. Ml plasma/min
2. A luminal cell membrane Na+ channel is the main pathway for sodium reabsorption in?
A. proximal tubule cells
B. thick ascending limb cells
C. distal convoluted tubule cells
D. collecting duct principal cells
E. collecting duct intercalated cells
D. Collectind duct principal Cells
Which of the following results in an increased osmotic gradient in the kidney?
a. Administration of a diuretic drug that inhibits Na+ reabsorption by thick ascending limb cells.
b. A low GFR (e.g., 20 mL / min in an adult).
c. Drinking a liter of water
d. Long loops of Henle
e. Low dietary protein intake
D. long Loops of Henle
a. Glomerular blood flow
b. Glomerular capillary pressure
c.GFR
d. Filtration fraction
e. Hydrostatic pressure in the space of Bowman’s capsule
A. Glomerular Blood Flow
The main driving force for water reabsorption by the proximal tubule epithelium is
a. Active reabsorption of amino acids and glucose
b. Active reabsorption of sodium
c. Active reabsorption of water
d. Pinocytosis
e. The high colloid osmotic pressure of in the peritubular capillaries
B. Active reabsorption of Sodium
What is the purpose of the countercurrent multiplication system?
a. store excess Na+ and urea
b. provide the Starling forces for proximal tubule fluid reabsorption
c. adjust GFR to match mean arterial pressure
d. provide a mechanism for excreting a dilute urine
e. provide osmotic forces for collecting duct water reabsorption
E. Provide osmotic forces for collecting duct water reabsorption