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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)
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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

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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

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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
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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