P a g e |1
Increase ADH
PHYSIO B 1.2 RENAL PHYSIOLOGY PT. 4 [DR. VILA]
FEU-NRMF INSTITUTE OF MEDICINE
11.11.14 [1MD-D]
Increase water reabsorption
Disorders of Urinary Concentrating Ability
Impairment in the ability of the kidneys to concentrate or dilute the
urine appropriately can occur with one or more of the following
abnormalities:
1. Inappropriate secretion of ADH
2. Impairment of the countercurrent mechanism. A
hyperosmotic medullary interstitium is required for
maximal urine concentrating ability. No matter how much
ADH is present, maximal urine concentration is limited by
the degree of hyperosmolarity of the medullary
interstitium.
3. Inability of the distal tubule, collecting tubule, and
collecting ducts to respond to ADH
Failure to produce ADH: Central Diabetes Insipidus
Also known ad pituitary diabetes insipidus
Hypothalamus or posterior pituitary gland fails to produce
or secrete ADH
Large volumes of dilute urine (can exceed 15L/day)
Inability of the kidneys to respond to ADH: Nephrogenic Diabetes
Mellitus
Normal or elevated levels of ADH are present
But renal tubules cannot respond
Can be caused by:
o Failure of countercurrent mechanism (Guyton)
o Failure of distal and collecting ducts to respond to
ADH (Guyton)
o Absence of V2 receptors for ADH (Accdg. to
Dr.Vila)
Large volumes of dilute urine
Can cause dehydration, unless fluid intake is increased by
the same amount as urine volume is increased
Diabetes: common manifestation is polyuria
Diabetes insipidus: secondary to ADH deficiency
Diabetes mellitus: secondary to glucose
No ADH Secretion / No response to ADH
Decrease reabsorption of water
Decrease urine volume
Increase urine tonicity
Supposedly.
Because of increase water reabsorption:
Increase BV
Increase BF
Increase GFR
Increase urine volume
Initially, there is an increase in water reabsorption
Eventually, the end effect will be an increase in urine
excretion due to increase blood volume
Osmoreceptor-ADH Feedback System
Example: Increase plasma osmolarity due to dehydration
o Fluid shift from the interstitium into the
intravascular compartment
o Osmoreceptors are located in the anterior
hypothalamus near the supraoptic nuclei
[Guyton]
o Osmoreceptors are sensitive to changes in
osmolarity
o An increase in extracellular osmolarity will cause
the osmoreceptors to shrink
o Sends signals to the hypothalamus to secrete ADH
o ADH enters blood stream towards the kidneys to
increase water reabsorption and decrease urine
volume
Increase Urine Volume
Decrease urine tonicity
The Syndrome of Inappropriate ADH Secretion (SIADH)
Plasma ADH elevated (as in sobrang taas, above what
would be expected on the basis of the body fluid osmolality
and, blood volume and pressure, kaya siya inappropriate)
Water is retained, hence body fluid becomes hypoosmotic
(more water, less concentrated ang body fluids)
Urine is hyperosmotic
The tonicity of plasma decreases due to dilutional
hyponatremia
However, the amount of sodium still falls within normal
range
It appears to be hyponatremic due to the increase in water
reabsorption (dilution)
Prepared by: Mar Mariano
P a g e |2
Edema
Excess fluid within the interstitial compartment producing
visible swelling
Increased capillary hydrostatic pressure
Decreased plasma colloid osmotic pressure
Edema caused by Heart Failure [Guyton, Chp. 25]
One of the most serious and most common causes of
edema
In heart failure, the heart fails to pump blood normally from
veins into the arteries, which raises the venous and capillary
pressures, which eventually increases capillary filtration
Increase capillary filtration lalabas ang fluid sa
interstitium edema
Heart failure can also decrease blood flow to the kidneys
Decrease blood flow decrease Na+ concentration
detected by macula densa secrete renin by JG cells
activate angiotensinogen to angiotensinogen I
conversion to angiontensin II by ACE in lungs release
aldosterone Increase salt and water retention
Increase BV Increase capillary hydrostatic pressure
Increase hydrostatic pressure edema
Edema caused by Decreased Plasma Proteins [Guyton, Chp. 25]
One of the most important causes of decreased plasma
protein concentration is loss of proteins in the urine
Nephrotic syndrome
The glomerular basement membrane widens, that allows
the filtration of proteins
Protein will therefore appear in the urine Proteinuria
Therefore, there will be a decrease in plasma proteins
Decrease plasma protein decrease plasma colloid
osmotic pressure edema
Lymphedema Failure of the Lymph Vessels to return fluid and
protein to the blood [Guyton, Chp. 25]
Plasma proteins tend to leak into the interstitium, which
can attract water and eventually cause edema
The proteins be removed through the lymphatics
Example of lymph obstructions are infections with filaria
nematodes (Wuchereria bancrofti)
o Blocks lymph vessels
o Causes lymphedema and elephantiasis
o Localized edema (limited to a one area only, [ex.]
Extremities, penis, breast)
Localized Edema
1. Venous obstruction
2. Capillary was damaged due to inflammation
3. Lymphatic obstruction
Generalized Edema
1. Increase capillary hydrostatic pressure
2. Decrease plasma albumin
Clinical Findings:
o Swelling in most dependent parts of the body due
to effects of gravity and increase hydrostatic
pressure in the capillaries
Edema vs. Effusion
Edema: fluid in interstitum
Effusion: fluid in potential spaces pleural, peritoneal,
pericardial cavities, joint spaces
Effect of Adding Saline Solution to the ECF [Guyton, Chp. 25]
Principle of osmosis
If a cell is placed in a hypotonic solution, the cell will swell
(movement of water from extracellular to intracellular)
However, the cell will not swell immediately
The cell will try to pump out electrolytes such as Na+, so
that water will follow these electrolytes out of the cell and
reduce swelling
This is called regulatory volume decrease (decrease cell
volume to reduce swelling)
If a cell is placed in a hypertonic solution, the cell will shrink,
but not immediately (movement of water intracellular to
extracellular)
Electrolytes from the solution will move into the cell, and
water will follow, hence reducing the shrinkage of the cell
This is called regulatory volume increase (increase cell
volume to reduce shrinkage)
Fluid INFLUX
Isotonic
Influx (2L
NSS)
Hypotonic
Influx (Water
loading)
Hypertonic
Influx (Drink
sea water)
ECF
Vol.
ECF
OP
H2O
Shift
ICF
Vol.
ICF
OP
Compensatory
Mechanism
SA
ME
NONE
SA
ME
SA
ME
NONE
Extra
to
intrace
llular
Intra
to
extrac
ellular
-Decrease ECF
tonicity
-Activate ADH
-Water
reabsorbed
-Decrease
urine volume
-Increase
urine tonicity
-Increase ECF
tonicity
-Inhibit ADH
-Increase
urine volume
-Decrease
urine tonicity
Prepared by: Mar Mariano
P a g e |3
Fluid EFFLUX
Isotonic
Efflux
(Burns)
Hypotonic
Efflux
(Profuse
Sweating)
Hypertonic
Efflux
(SIADH)
ECF
Vol.
ECF
OP
H2O
Shift
ICF
Vol.
ICF
OP
Compensatory
Mechanism
SA
ME
NONE
SA
ME
SA
ME
NONE
Intra
to
extrac
ellular
Extra
to
intrace
llular
-High ECF
tonicity
-Activate ADH
-Water
reabsorption
-Decrease
urine volume
-Increase
urine tonicity
-Low ECF
tonicity
-Inhibit ADH
-Increase
urine volume
-Decrease
urine tonicity
Acid-Base Balance
Acid: a substance that can release or donate hydrogen ion
[H+]
Base: a substance that can combine with or accept
hydrogen ion [H+]
Normal blood pH: 7.35 7.45
Normal pCO2: 35 45 mmHg
Normal pCO3-: 22 26 mmHg
pO2 is less important
*Respi Physio Review*
Oxygen-Hemoglobin Dissociation Curve
Hemoglobin carries oxygen
However, hemoglobin never reaches 100% oxygen
saturation. Why?
o All the blood that reaches the lungs will be 100%
oxygenated
o From the lungs, and along with the blood from
different veins, will drain into the heart
o Veins carry less oxygenated blood
o Blood that comes out of the aorta will only be 9798% saturated with oxygen because it will be
mixed with less oxygenated blood from the veins
o At 60mmHg, the saturation slows down
o Below 60mmHg, saturation is steep (Hgb unbinds
immediately from oxygen)
o In real situations, we never go below 60mmHg
Rules:
pCO2: respiratory component
o Represent acid
o Excreted by lungs
o Increase pCO2: Acidic
o Decrease pCO2: Basic
pCO3-: metabolic component
o Represent base
o Excreted by kidneys
o Increase pCO3-: Basic
o Decrease pCO3: Acidic
Decrease pH: acidosis
Increase pH: alkalosis
Always follow the pH
If fully compensated: pH will go back to normal
o If pH is slightly toward alkaline but within normal
range: alkalosis, fully compensated
o If pH is slightly toward acidic but within notmal
range: acidosis, fully compensated
If partially compensated: pH of blood is still abnormal
pCO2
pH
(35 45
mmHg)
(7.35 7.45)
pCO3(22 -26mmHg)
7.29
Acidic
48
Acidic
24
Normal
7.29
Acidic
37
Normal
19
Acidic
7.47
Basic
32
Basic
24
Normal
7.47
Basic
37
Normal
29
Basic
7.29
Acidic
36
Normal
19
Acidic
7.47
Basic
32
Basic
19
Acidic
7.47
Basic
48
Acidic
29
Basic
7.29
Acidic
30
Basic
28
Basic
7.47
Basic
30
Basic
19
Acidic
7.44
Normal
48
Acidic
30
Basic
7.38
Normal
48
Acidic
30
Basic
Disorder
Respiratory
Acidosis
Metabolic
Acidosis
Respiratory
Alkalosis
Metabolic
Alkalosis
Metabolic
Acidosis
Respiratory
Alkalosis,
partially
compensated
by the
kidneys
Metabolic
Alkalosis,
partially
compensated
by lungs
Mixed
Acidosis,
partially
compensated
Respiratory
Alkalosis,
partially
compensated
Metabolic
Alkalosis,
fully
compensated
Respiratory
Acidosis, fully
compensated
Prepared by: Mar Mariano
P a g e |4
Kidneys
o Third line of defense
o Remove excess H+ from the body in combination
with urinary buffers
Henderson-Hasselbach Equation
Shows that the pH of a solution is determined by the pKa of
acid and the ratio of the concentration of conjugate base Aand acid HA
Bicarbonate Buffer System: Kidneys [Berne&Levy Chp. 36]
pH Units
In the events of everyday life, the variation of ECF pH is very
narrow
1nmol of H+/L = 0.01 pH unit
o If H+ ions increase: pH decrease, pH is acidic
o If H+ ions decrease: pH increase, pH is basic
In abnormal situations, much wider changes may be seen.
In practice, a pH of 6.8 or 7.8 will only be seen in profound
pathologic situations
Sources of H+ ions in the body
Metabolism of food stuffs
o Produces 300L of CO2
Incomplete metabolism of CHO and fats
o Produces nonvolatile acids
o Lactic acid from glucose, acetoacetic acid and
Beta-hydroxybutyric acid from fatty acid
oxidation
Oxidation of proteins and amino acids
o Produces strong acids
o H2SO4, HCl and H3PO4
Bodys defenses against changes in blood pH
Chemical buffers in ECF, ICF and bone
o First line of defense of blood pH
o Minimized a change in pH but cannot remove acid
or base from the body
Respiratory system
o Second line of defense
o Large loads of acid stimulate breathing which
removes CO2 from the body
The most important ECF buffer
In the proximal tubules:
The proximal tubule reabsorbs the largest portion of the
filtered load of HCO3
H+ secretion across the apical membrane of the cell occurs
by Na+H+ antiporter and H+-ATPase
Carbonic anhydrase are present in the brush borders that
convert H2CO3 to water and carbon dioxide
They enter the cells and combines to produce H+ and HCO3
by carbonic anhydrase
H+ is secreted via apical membrane, HCO3- via basolateral
membrane
HCO3 exit via a symporter: 1Na+ with 3HCO3
Some of the HCO3 may exit in exchange for Cl
A K+-HCO3- symporter in the basolateral membrane may
also contribute to the exit of HCO3- from the cell
In the collecting ducts
There are 2 types of cells:
o Principal cells responsible for electrolyte and fluid
absorption
o Intercalated cells for acid-base balance
There are 2 types of intercalated cells
o Alpha-intercalated cells: secrete H+ (reabsorbs
HCO3-)
o Beta-intercalated cells: secrete HCO3
Within Alpha-intercalated cells:
o H+ and HCO3- are produced by the hydration of
carbon dioxide, which is catalyzed by carbonic
anhydrase
Prepared by: Mar Mariano
P a g e |5
H+ is secreted into the tubular fluid via:
Apical membrane H+-ATPase
H+,K+-ATPase
o HCO3- exits across the basolateral membrane in
exchange for Cl-, via a Cl-HCO3- antiporter
o Active during metabolic acidosis
Within Beta-intercalated cells
o H+-ATPase is located in the basolateral
membrane
o Cl-HCO3- antiporter is located in the apical
membrane
[Baliktad sila ng alpha-intercalated]
o Activity of beta-intercalated cells is increased
during metabolic alkalosis, when the kidneys
must excrete HCO3Acid-Base Balance via excretion of ammonium
NH4+: ammonium, acidic
NH3: ammonia
NH4+ is produced by the kidneys by the metabolism of
glutamine
The kidneys metabolize glutamine, excrete NH4+, and add
HCO3- to the body
If NH4+ is not excreted in the urine, it is converted into urea
by the kidneys, which produces H+, and eventually buffered
by HCO3
Production of urea, therefore, consumes HCO3- and inhibits
HCO3- formation through the synthesis and excretion of
NH4+
NH4+ is produced from glutamine via ammoniagenesis
One glutamine molecule produces two NH4+ molecules and
two HCO3- molecules
HCO3- exits the cells across the basolateral membranes and
enters the peritubular blood
NH4+ exits via apical membrane and enters the tubular
fluid, via NA+-H+ antiporter, but NH4+ is substituted for H+
NH3 is freely permeable and can diffuse out of the cell
where it is protonated into NH4+
The thick ascending limb is the primary site of NH4+
reabsorption, with NH4+ substituting for K+ on the 1Na+K+-2Cl- symporter
The NH4+ that is reabsorbed, accumulates in the medullary
interstitium which is then secreted into the collecting ducts
via:
o Nonionic diffusion
o Diffusion trapping
NH3 diffuses from the medullary interstitium into the
collecting ducts (nonionic diffusion)
The presence of Alpha-intercalated cells which secrete H+
ions will protonate the NH3 to become NH4+
Since NH4+ is less permeable in the collecting ducts, it is
trapped in the tubular lumen (diffusion trapping)
It is then eliminated from the body via the urine
Please refer to Guyton for the Phosphate Buffer System and Proteins
as ICF buffers, and Guyton Chp. 36 Acid-Base Balance (Hindi na
diniscuss ni doc, pero kasama daw sa shifting )
Reading assignments:
Renal Failure
Renal Endocrine Function
Sources:
Lecture: Dr. Vila
Berne&Levy, 6th Edition
Guyton and Hall, 12th Edition
Read Berne & Levy or Guyton, guys! Mas specific at complete mga
explanations dun. Good luck and God bless! Labyu all <3
Prepared by: Mar Mariano
