Transcript 19 Comp Review 3b

Respiratory Physiology
1
CO2 Transport
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When oxygen is on the hemoglobin molecule, it is called
oxyhemoglobin.
Dissociation of oxyhemoglobin is when the oxygen is
released and enters the tissues.
This dissociation increases as the pCO2 levels increase.
In other words, when the carbon dioxide levels rise,
oxygen will jump off the hemoglobin and into the
tissues. Therefore, the most effective stimulus to the
respiratory center is an increase in pCO2.
The waste product of cellular respiration is carbon
dioxide.
CO2 will then attach onto the hemoglobin and be taken
to the lungs to be expelled.
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CO2 Transport
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CO2 is carried to the lungs on the hemoglobin, after the oxygen has
left to enter the tissues.
The carbon dioxide reacts with water in the RBC to form carbonic
acid, which then breaks apart into a hydrogen ion (which lowers
blood pH) and a bicarbonate ion (which raises blood pH).
CO2 + H2O  H2CO3  H+ + HCO3-
This reaction is reversible, and would go mainly to the right in the
tissues and to the left in the lungs.
CO2 is transported in the blood predominately in the form of
bicarbonate.
The number of H+ ions in the blood depends partly on the amount of
CO2 in the blood. The more CO2 in the blood, the more H+ in the
blood, which makes the blood acidic. If the blood is too acidic,
bicarbonate ions are absorbed to raise the pH. If the blood is to
alkaline, bicarbonate ions are excreted by the kidneys.
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Respiratory System Contribution to
pH Balance in the Blood
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If a person has excess H+ ions in the blood (acidosis),
they will breathe more rapidly.
If the person has an airway obstruction (such as
asthma), they cannot exhale the excess CO2.
Because the H+ are building up, the carbonic acid will
also build up, causing a drop in pH (acidosis) in the
blood.
Enzymes in the body cannot work outside of their
optimal pH range, so chemical reactions come to a halt.
Hyperventilation results in too little CO2 in the blood, so
the person has a high pH (alkalosis), which also
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denatures enzymes.
Control of Respiration
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Relaxed breathing only requires the
diaphragm to contract for inspiration, and
for the diaphragm to relax for expiration.
Forced breathing requires the diaphragm
plus muscles that raise and lower the ribs
(external intercostals for inspiration,
internal intercostals for expiration).
The respiratory centers are most sensitive
to the level of CO2 in the blood, rather
than the levels of oxygen.
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Control of Gas at Cellular Level
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The flow of blood through capillaries is
controlled by sphincters on the arterioles and
capillary beds to adjust the amount of blood
flowing to particular tissues.
Cells and tissues that are undergoing increased
aerobic activity have less oxygen and more CO2,
lower pH, and increased temperature.
When the CO2 levels in the tissues are too high,
the smooth muscle sphincters relax to allow
more blood flow to increase gas exchange.
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Boyle's Law
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P1V1=P2V2
Pressure and volume are inversely related (if
other variables are kept constant.)
Boyle’s Law
assumes normal
circumstances,
not a person
who is in high
altitude or who
has variation in
body
temperature.
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Air Pressure in Lungs
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Every time a molecule strikes the wall of a
container, it causes pressure. In a larger
container with fewer molecules, it takes a while
to strike the wall randomly, so there is less
pressure.
The number of impacts on a container wall is
the pressure.
The lungs must have a volume change to create
a pressure change, which is required to have air
move into and out of the lungs.
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Air Pressure in Lungs
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The diaphragm is the muscle that mostly
contributes to the volume change. When it
contracts, it pulls downward, and the
volume of the thoracic cavity increases.
The external intercostals elevates the
ribcage, giving the lungs more room, so
they also increase the lung volume.
Those two muscles cause increased
volume.
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Air Pressure in Lungs
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Because the lungs are tethered to the thoracic cavity,
when your chest wall expands, your lungs expand with
it. The lungs are stuck to the chest wall because the
serous fluid in the pleural cavity makes the lungs stick to
the chest wall like two pieces of wet glass stuck
together.
When the lungs expand, their volume expands. That
means there is less pressure in the lungs than there is in
the outside air. Since air moves from high to low
pressure, air flows into the lungs.
As air flows in, the alveoli expand, so the volume in each
air sac expands, so the pressure in the alveoli lowers. Air
in the conducting passages (bronchi) is at higher
pressure, so it will move from high to low pressure
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areas. Therefore, air will move into the alveoli.
Air Pressure in Lungs
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We are looking at two types of air
pressures: atmospheric pressure, and the
pressure of air deep in the lungs, called
the alveolar (pulmonary) pressure.
As long as there is a difference in pressure
between these two, there will be a
pressure gradient, and air will flow.
If they equal each other (such as during a
punctured lung, called a pneumothorax),
air will not flow.
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Left shift
CAUSE:
pH increased
CO2 decreased
Temperature decreased
CAUSE:
pH decreased
CO2 increased
Temperature increased
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Right shift
CAUSE:
pH increased
CO2 decreased
CAUSE:
pH decreased
CO2 increased
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Shifts
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A left shift will increase oxygen's affinity for hemoglobin.
 In a left shift condition (alkalosis, hypothermia, etc.)
oxygen will have a higher affinity for hemoglobin (it
won’t leave!).
 This can result in tissue hypoxia even when there is
sufficient oxygen in the blood.
A right shift decreases oxygen's affinity for hemoglobin.
 In a right shift (acidosis, fever, etc.) oxygen has a
lower affinity for hemoglobin. Blood will release
oxygen more readily.
 This means more O2 will be released to the cells, but
it also means less oxygen will be carried from the
lungs in the first place.
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What happens if the lung dissociates from the chest wall?
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Pneumothorax: air in the pleural cavity
Hemothorax: blood in the pleural cavity
How?
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Injury (Gun shot, stabbing)
Spontaneous (tissue erosion, disease lung)
Bleeding wound
Chest wall recoils outward (barrel chest)
Lung recoils inward (atelectasis = alveolar, lung collapse)
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Emphysema
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COPD (chronic obstructive pulmonary disease) is
emphysema plus chronic bronchitis.
Emphysema is generally caused by smoking.
The alveoli have broken, leaving spaces where
gas exchange cannot take place.
Compliance decreases, so It is difficult to expel
the air in the lungs.
Each inhalation is a forced inspiration also.
When the ribs are continually raised with each
breath, they eventually remain in the upright
position, causing a barrel chest.
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Exhalation Problem: COPD
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Normal exhalation is
passive, requires no
ATP. But forced
expiration (such as
emphysema patient)
recruits abdominal
muscles. The muscles
enlarge with time,
creating a barrelshaped chest, typical
of emphysema
patients and COPD.
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COPD
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In everyone, the midsized bronchioles do not have
cartilage rings to hold them open, and during exhalation,
the sides of the bronchioles collapse and touch each
other.
If there is not enough surfactant, they stick to each
other with greater strength (like two wet pieces of
glass), and the person has to forcefully exhale with each
breath to overcome the cohesiveness of the fluid.
Surfactant is like adding soap to the fluid so the surfaces
come apart easier.
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Exhalation
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Giving oxygen in high concentration helps get air into
their lungs, but it reduces the drive for them to breathe.
CO2 is a powerful driving force for ventilation. When a
person has COPD, they have less CO2, and oxygen
becomes the driving force.
If we give them oxygen, the drive for them to breathe
becomes diminished. They eventually wind up on a
positive pressure ventilator, but the disease progresses,
and they die from suffocation.
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Acute Mountain Sickness
(Altitude Sickness)
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When you visit someone in a high elevation (5,000 m)
you might get acute mountain sickness.
Symptoms:
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Cause:
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Severe headache, fatigue, dizziness, palpitation and nausea.
Pulmonary edema.
Why do you get pulmonary edema?
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High elevations have lower pO2 levels.
This causes hypoxia (lack of oxygen) in the pulmonary capillaries
This causes increased pulmonary arterial and capillary pressures
(pulmonary hypertension)
That causes the pulmonary edema
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Ventilation Volume
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When you breathe in, you inhale about 500 ml. You exhale about
500 ml. Therefore, 500 ml is your TIDAL VOLUME.
Not all 500 ml gets down deep to your alveoli. About 150 ml of it
stays in the conductive zone (bronchi and trachea). About 350 ml
reaches the alveoli. That is considered your alveolar ventilation
volume.
That is the amount of air that can undergo gas exchange. If you
want to calculate how much air moves in and out per minute, take
the tidal volume and multiply it by breathing rate (about 12 breaths
per minute for adult, 20 for children).
500 x 12 = total ventilation
Tidal volume – 150 x 12 = alveolar ventilation
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Obstructive Lung Diseases
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Obstructive lung diseases are
characterized by inflamed and easily
collapsible airways, obstruction to airflow,
and frequent hospitalizations.
Examples
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Asthma
Bronchitis
Chronic obstructive pulmonary disease
(COPD)
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Restrictive Lung Diseases
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These are extrapulmonary or pleural respiratory diseases
decreased
lung volume (rapid, shallow breathing), an
increased work of breathing, and
inadequate ventilation and/or
oxygenation. Decreased vital capacity.
that restrict lung expansion, resulting in a
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Cystic Fibrosis
Infant Respiratory Distress Syndrome
Weak respiratory muscles
Pneumothorax
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Capacities are two or more volumes added together
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You don’t need to memorize the normal numbers, just the definitions
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Respiratory Cycle: A single cycle of inhalation and exhalation
Respiratory rate: number of breaths per minute (usually about 12-18;
children higher 18-20).
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Tidal Volume: normal breath in and out. Usually about 500 ml.
Inspiratory Reserve Volume: take in a normal breath, stop, now inhale
as much more as you can. In other words, this is the amount of air that can
be forcefully inhaled after a normal inhalation. This is your tidal volume in
plus your inspiratory volume.
Expiratory Reserve Volume (Expiratory capacity): take a normal
breath in, a normal breath out, then breathe out the most you can. In other
words, this is the amount of air that can be forcefully exhaled after a
normal exhalation. This is the air needed to perform the Heimlich
maneuver. The maneuver decreases the thoracic cavity volume, causing
increased pressure in lungs. That causes forced air with high pressure to be
expelled from the lungs.
Residual volume: The amount of air left in your lungs after you exhale
maximally. This air helps to keep the alveoli open and prevent lung
collapse. This is estimated based on height and age
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You don’t need to memorize the normal numbers, just the definitions
Vital
capacity: The volume of air a patient can exhale maximally after a
forced inspiration. Maximum deep breath in, then exhale as much as possible.
It can be used to determine if problems are obstructive (normal) or restrictive
(reduced). Vital capacity divided by expiratory reserve volume should be 80%.
Total Lung Capacity (TLC): the sum of all lung volumes
Inspiratory Capacity: amount of air for a deep breath in after normal
exhalation
Functional residual capacity: amount of air left in your lungs after a
normal exhale. You have to calculate this:
FRC = ERV + residual volume.
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In COPD, their FRC increases.
They have a barrel chest
The lungs don’t have as much recoil, have decreased tidal volume, cannot exhale enough
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You don’t need to memorize the normal numbers, just the definitions
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Dead Space: Area where air fills the passageways and never contributes
to gas exchange. Amounts to about 150 ml.
Minute Respiratory Volume (MRV): tidal volume x respiratory rate. This
calculation does not take into account the volume of air wasted in the dead
space. A more accurate measurement of respiratory efficiency is alveolar
ventilation rate.
Alveolar Ventilation Rate (AVR)
AVR = (TV – Dead Space) x Respiratory Rate
Summary of lung calculations
FRC = ERV + RV
TLC = RV + ERV + TV + IRV
MRV = TV x RR
AVR = (TV – Dead Space) x RR
You DO need to
know these
formulas.
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Sample Questions
Minute Respiratory Rate is the volume of air that enters the airways (passes the
lips) each min.
MRV = Tidal volume x rate of breathing
= (500 ml/breath) x 12 breaths/min
= 6,000 ml/min
Alveolar ventilation rate is the volume of air that fills all the lung’s
respiratory airways (alveoli) each min. In a normal, healthy lung, this might
be:
AVR = (tidal volume – dead space volume) x rate of breathing
= (500 ml/breath – 150 ml) x 12 breaths/min
= (350 ml/breath) x 12 breath/ min
= 4, 200 ml/min
In a diseased, poorly perfused lung, this value may well be much lower.
Then, is panting an example of hyper, normal, or hypoventilation????
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Respiratory vs. Metabolic
Acidosis and Alkalosis
RESPIRATORY ACIDOSIS AND ALKALOSIS is abnormal blood pH which is
caused by abnormal breathing rates. It is not necessarily a disease, since
hyperventilating from stress is not a disease.
Respiratory alkalosis is caused by hyperventilation. This increases the amount of
CO2 that you are exhaling. CO2 is an acid, so if you hyperventilate, you are exhaling a
lot of acid, so your blood plasma pH will increase (alkalosis)
Respiratory acidosis is caused by hypoventilation. This decreases the amount of
CO2 that you are exhaling. If you hypoventilate, you are not exhaling enough acid, so
your blood plasma pH will decrease (acidosis). Respiratory acidosis can also be
caused by interference with respiratory muscles by disease, drugs, toxins.
METABOLIC ACIDOSIS AND ALKALOSIS is abnormal blood pH which is not
caused by abnormal breathing rate.
Metabolic acidosis can be caused by
 Salicylate (aspirin) overdose
 Untreated diabetes mellitus (leading to ketoacidosis)
Metabolic alkalosis can be caused by
 excessive vomiting (loss of acid from stomach)
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Compensations for Respiratory vs.
Metabolic Acidosis and Alkalosis
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Respiratory alkalosis can be compensated by
 excreting an alkaline urine
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Respiratory acidosis can be compensated by
 excreting an acidic urine
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Cannot hypoventilate since hyperventilation is the problem in the first
place!
Cannot hyperentilate since hypoventilation is the problem in the first
place!
Metabolic acidosis can be compensated by
 excreting an acidic urine
 hyperventilation
Metabolic alkalosis can be compensated by
 Excreting an alkaline urine
 Hypoventilation
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Acid-Base Conditions
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Excessive diarrhea
Causes the problem of low HCO3 (bicarbonate)
Leads to pH in blood (acidosis)
Lungs Compensate by:
pCO2 (hyperventilation, which decreases the CO2
content in the blood, thereby removing acid
from the blood)
Kidneys can also compensate by increasing bicarbonate
reabsorption.
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Acid-Base Conditions
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Ingesting excessive stomach antacids
Causes the problem of high HCO3 (bicarbonate)
Leads to pH in blood (alkalosis)
Lungs Compensate by:
pCO2 (hypoventilation, which increases the CO2
content in the blood, thereby adding acid
from the blood)
Kidneys can also compensate by increasing acid secretion.
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Acid-Base Conditions
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Aspirin overdose
Causes the problem of high acid, low HCO3 (bicarbonate)
Leads to pH in blood (acidosis)
Lungs Compensate by:
pCO2 (hyperventilation, which decreases the CO2
content in the blood, thereby removing acid
from the blood)
Kidneys can also compensate by increasing bicarbonate
reabsorption.
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Acid-Base Conditions
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Hyperventilation from fear or pain
Causes the problem of  pH in blood (alkalosis) from CO2 being
exhaled.
The lungs are the problem, so the lungs cannot compensate.
However, the kidneys can compensate by:
 HCO3 secretion, which increases the concentration of acid in
the blood.
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Pulmonary Embolism
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Pulmonary Embolism: blockage of the pulmonary
artery (or one of its branches) by a blood clot, fat, air or
clumped tumor cells. The most common form of
pulmonary embolism is a thromboembolism, which
occurs when a blood clot, generally in a vein, becomes
dislodged from its site of formation, travels to the heart,
goes into a pulmonary artery, and becomes lodged in
the smaller artery in the lungs, blocking blood flow and
oxygen to that region of the lung.
Symptoms may include difficulty breathing, pain during
breathing, and possibly death. Treatment is with
anticoagulant medication.
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Renal Physiology
PART ONE
Renal Physiology Overview
PART TWO
Renal Clearance
PART THREE
Renal Acid-Base Balance
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Role of Kidneys
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The kidneys can adjust blood volume, blood pressure, and
blood composition
BLOOD VOLUME
 Adjusts the volume of water lost in urine by
responding to ADH, aldosterone, and renin
BLOOD PRESSURE
 Releasing renin and adenosine (increases blood
pressure)
BLOOD COMPOSITION
 Releasing erythropoietin (increases RBC production)
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Sympathetic Nervous System
Effect on Kidneys
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Changes the rate of blood flow (and
therefore, the pressure) to the glomerulus
by telling the precapillary sphincters when
to contract or relax.
Sympathetic nervous system is stimulated
by renin, which is released by the kidney.
Causes changes in water and sodium
reabsorption by the nephron
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pH Imbalances
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Many things can alter the pH of the blood
Beverages we drink
 Acids produced by metabolism
 Breathing rate
 Vomiting (loss of acid)
 Diarrhea (loss of base)
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pH imbalances are dangerous because
many enzymes only function within a
narrow pH range.
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Renal Physiology
Basic Mechanisms
of Urine Formation
1)
2)
3)
4)
Glomerular filtration
Tubular reabsorption
Tubular secretion
Excretion
How do we determine
these rates?
Master formula
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Glomerular Filtration
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The capillaries in the glomerulus contain many
holes, called fenestrations. As blood passes
through the glomerulus, the plasma passes
through the fenestrations. Proteins and other
large substances do not cross through; they stay
in the bloodstream.
The filtered plasma leaves the bloodstream in
this way, and enters the glomerular capsule, and
then enters the proximal convoluted tubule.
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Glomerular Filtration Rate
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GFR is used as a measure of kidney function.
Normal GFR is 125 ml per minute for both kidneys
combined.
That means 7.5 liters per hour, or 180 liters per day.
That is 45 gallons of filtrate produced per day!
Of course, most of that is reabsorbed.
Average urine output is about 1.2 liters per day.
That means you need to drink 1.2 liters of fluid per day
(remember that caffeine and alcohol are diuretics, so
you need more than that to compensate if you drink
those beverages). You need to drink more (about 2
liters per day) if you are getting a cold or flu.
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Altering GFR
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Several different mechanisms can change
the diameter of the afferent and efferent
arterioles to alter the GFR:
Hormonal (hormones)
Autonomic (nervous system)
Autoregulation or local (smooth muscle
sphincters around the arterioles or
capillaries near the glomerulus)
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Remember the route the fluid takes:
Glomerulus 
Proximal convoluted tubule (PCT) 
Descending limb of LOH 
Ascending limb of LOH 
Convoluted tubule 
Collecting duct
Tubular Reabsorption
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This is the process by which substance in the renal tubules are
transferred back into the bloodstream. Reabsorption is the removal
of water and solute molecules from filtrate after it enters the renal
tubules.
Fluid goes from the glomerulus to the proximal convoluted tubule
(PCT), down the loop of Henle and back up, then into the distal
convoluted tubule (DCT), and into the collecting duct.
In the PCT, the nutrients are reabsorbed. If there are more
nutrients than can be reabsorbed (such as excess sugar), it will be
excreted in the urine.
When the nutrients are reabsorbed (in the PCT), the inside of the
tubule will have more water and less nutrients. Since water goes to
the area that has a higher concentration of particles (osmosis),
water will also leave the tubules; this occurs in the DCT.
By the time the fluid has reached the collecting duct, nothing but
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waste products are left, such as urea, ammonia, and bilirubin.
Tubular Reabsorption
 Capillaries follow the renal tubules
and wrap around them.
 The straight capillaries that travel
longitudinally next to the tubules are
called vasa recta, and the capillaries
that wrap around the tubule are
called peritubular capillaries.
 There is a space between the
capillaries and the tube, called the
peritubular space.
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Tubular
Reabsorption
Tubular
Cells
Peritubular
Capillaries
Filtrate arriving from
Bowman’s Capsule
Lumen of
Tubule
 The peritubular capillaries are nearby, and the particle
concentration is low inside of them. Therefore, the particles in the
peritubular space (high concentration of particles) will leave that
space and enter into the peritubular capillaries by osmosis.
 That is how the nutrients are reabsorbed from the tubules back into
the bloodstream.
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Tubular Reabsorption
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The ascending limb of the Loop of Henle and the DCT are
impermeable unless hormones cause substances to be moved
through their walls.
If the blood is low in sodium, (after excessive sweating),
aldosterone (from the adrenal cortex) will cause more sodium to be
pumped out of the tubule and into the peritubular space. The
sodium will then enter the capillaries.
Since water follows where salt goes, whenever the body needs
more water (such as dehydration), ADH is released (from the
neurohypophysis = posterior pituitary). ADH is also called
vasopressin.
Aldosterone and ADH will increase blood volume, increasing blood
pressure.
These two hormones begin their action in the ascending limb and
continue to work in the DCT.
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Tubular Secretion
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Some substances are unable to filter through the
glomerulus, but are not wanted by the body.
Examples are pollutants like pesticides, and
many drugs, such as penicillin and non-steroidal
anti-inflammatory drugs (NSAID’s).
As blood passes through the peritubular
capillaries, those substances are moved from the
capillaries directly into the PCT and DCT.
This is called tubular secretion.
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Juxtaglomerular Apparatus
 The distal end of the
renal tubule passes
next to the glomerulus
to form the
juxtaglomerular
apparatus (juxta
means “next to”).
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Juxtaglomerular Apparatus:
Alters BP and GFR by autoregulation
 Two types of cells:
 1) Macula densa cells
 2) Juxtaglomerular cells
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Juxtaglomerular Apparatus: Macula
Densa Cells
 If blood pressure is too
low, the macula densa
releases adenosine,
which causes
vasoconstriction of
the afferent arteriole.
This will slow the GFR,
so less water is lost,
and blood pressure
increases.
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Juxtaglomerular Apparatus: Macula
Densa Cells
 If blood pressure is too
high, the macula
densa stops releasing
adenosine, which
allows the sphincters
to relax.
 This will increase GFR
so more water is lost,
and blood pressure
decreases.
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Juxtaglomerular Apparatus:
Juxtaglomerular Cells
 Juxtaglomerular cells
secrete renin if the blood
pressure is still too low
after adenosine has
caused vasoconstriction.
 Renin causes more
sodium to be reabsorbed,
and water follows, so
blood volume increases,
so blood pressure
increases.
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Summary of Autoregulation
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The nephron can alter the blood pressure and flow into the
glomerulus by autoregulation.
The JGA senses the blood pressure going into the glomerulus and
the flow rate of the fluid going through the renal tubule. If the GFR
is too low, the JGA (macula densa) will cause the pre-capillary
sphincters on the nearby arterioles to contract, increasing blood
pressure, like turning up the faucet on a hose.
If that restores the desired filtration rate and flow, no further action
is needed. If not, the kidneys produce the enzyme renin, which
makes the lungs produce angiotensin converting enzyme (ACE),
which turns A1 into A2, which constricts blood vessels, and also
causes the release of aldosterone, raising the blood pressure.
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Hormonal Regulation
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If a person sweats from activity, eats very salty food, or has
diarrhea, it changes the sodium and water content of the plasma.
Two hormones that affect the ascending limb of the Loop of Henle
are aldosterone and antidiuretic hormone (ADH).
Adosterone is produced by the adrenal cortex and causes additional
sodium ions to be pumped our of the tubule and into the
bloodstream. Water comes with it by osmosis, and the blood
pressure increases.
ADH is produced by the posterior pituitary gland and causes
retention of additional water from the DCT and collecting ducts.
Sodium is not included in this process, so the result is to dilute the
plasma during dehydration, when the plasma is becoming to
concentrated with particles.
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Erythropoietin
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The kidneys also monitor the oxygen
content of the blood.
If O2 levels are low, the JGA releases
erythropoietin to stimulate the bone
marrow to produce more red blood cells.
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Neural Regulation
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The kidneys receive about 22% of the blood pumped out
of the heart, so that is a substantial quantity passing
through the kidneys at any given time.
If there is a stressor and the sympathetic nervous
system causes us to go into fight or flight mode, the
skeletal muscles need to have a maximum amount of
blood flow.
Neurons from the sympathetic nervous system innervate
the kidneys to decrease renal blood flow during critical
situations.
58
Urine






Urine contains ions such as sodium, chloride, and potassium, as well
as suspended solids, known as sediments, such as cells, mineral
crystals, mucus threads, and sometimes bacteria.
The pH of urine is normally 4.6-8
A urinalysis can identify abnormal processes occurring in the body.
Because urine is a waste product, its contents are influenced by the
foods and drinks we ingest.
We may lose fluid elsewhere, such as through sweating or diarrhea,
which causes the urine to become more concentrated.
Acids produced through metabolism can also change the pH of our
urine. Even changes in breathing rate can change the urine pH as
excess acids or bases are excreted to maintain normal plasma pH.
59
Abnormal Urinalysis

These substances should not be in the
urine. When they are, it is abnormal.






Glucose
Blood
Protein
Pus
Bilirubin
Ketones
60
Causes of abnormal UA






Glucose: diabetes mellitus
Blood: bleeding in urinary tract from
infection or kidney stone
Protein: kidney disease, hypertension,
excessive exercise, pregnancy
Pus: bacterial infection in urinary tract
Bilirubin: liver malfunction
Ketones: excessive breakdown of lipids
61
Micturition




Urination is technically known as micturition.
Once the volume in the urinary bladder exceeds 200 ml
stretch receptors in its walls send impulses to the brain,
indicating the need to eliminate.
When you make the decision to urinate, the
parasympathetic nervous system stimulates the smooth
muscle in the urinary bladder’s internal sphincter to
contract.
Remember, the internal sphincter is smooth muscle
(involuntary) and the external sphincter is skeletal
muscle (voluntary). Both must relax for urine to exit.
62
Diuretics for hypertension and
congestive heart failure




Diuretics decrease plasma volume. This group of drugs are thiazide
diuretics (such as Lasix). They inhibit the reabsorption of sodium
and potassium from the renal tubule, causing more water to pass
out as urine.
Compared to sodium, the homeostatic range of potassium is quite
narrow.
Lasix (Furosemide) inhibits reabsorption of potassium more than
other diuretics. Low blood levels of potassium are called
hypokalemia. It is important for someone on Lasix to take
potassium supplements or eat fruits or vegetables that have a lot of
potassium (such as cantaloupe).
However, too much potassium from excessive supplements can
have fatal side effects.
63
Diuretics




Furosemide (Lasix)
Mannitol
Spironolactone
Amiloride
64
Homeostasis





Maintaining the proper concentration of sodium and water is critical.
If the plasma is too concentrated with particles, nearby cells can
shrink and lose their function.
If the plasma is too dilute, water can enter the nearby cells and
cause them to expand, also decreasing their function.
This is especially dangerous in the brain.
Studies have shown a close link between obesity, diabetes, and
kidney disease. Exercise helps maintain normal kidney function by
increasing blood flow, and it decreases the incidence of high blood
pressure. People receiving dialysis and those who have had kidney
transplants especially need to exercise.
65
Renal Physiology
PART TWO
Renal Clearance
66
How to calculate Tubular Load


If we want to know how much glucose was filtered into the
nephron, we need to know that person’s blood plasma glucose
levels, and we would need to calculate their GFR.
Each individual solute will have its own tubular load calculation.
TL
glucose
= Pglucose x GFR
TL
sodium
= Psodium x GFR
chloride
= Pchloride x GFR
TL
Renal Equations
For any substance,
The rate of
excretion
= rate of +
filtration
(Urinary output)
(GFR or TL)
rate of –
secretion
rate of
reabsorption
Other terms that are used to express these ideas:
•For “Rate of excretion” we often use the term “urinary output”
•For “Rate of filtration,”
when referring to filtered fluid, we often use the term GFR (glomerular
filtration rate)
if referring to filtered solute, we use TL (Tubular Load)
68
Solutes are reabsorbed into the
blood stream


The next photo is of a Proximal Convoluted Tubule
(PCT), just beyond the glomerulus. The lumen of the
tubule contains the filtrate which leaked out of the
capillaries and into the glomerulus, entered Bowman’s
capsule, and has now arrived in the PCT.
There are cells (tubular cells) lining the lumen of the
PCT. The cells have proteins that allow some solutes to
diffuse into the cell, and right back out cell, and into the
peritubular capillaries that surround the PCT. In that
way, solutes re-enter the blood stream.
69
Filtrate arriving from
Bowman’s Capsule
Peritubular
Capillaries
Tubular
Cells
Lumen of
PCT
70
Peritubular capillaries
71
Proximal Convoluted Tubule





Water will follow the solutes.
The PCT is the biggest site for reabsorption of
solutes (substances dissolved in water).
100% of glucose and amino acids are reabsorbed
in the PCT.
67% of Na and water are reabsorbed here.
If ADH levels are very high, most of the water will be
reabsorbed in the PCT.
 Water reabsorption along the proximal convoluted tubule (PCT) occurs by
osmosis resulting primarily from reabsorption of sodium
72
Proximal Convoluted Tubule



In a state of acidosis, the PCT will secrete H+ ions.
When the H+ ions are secreted, reabsorption of
bicarbonate ions occurs at the same time.
H+ ions are also secreted in the DCT, but bicarbonate
cannot be reabsorbed there.
73
Glucose reabsorption



Glucose and amino acids leave the tubule and enter the
peritubular capillaries. That is reabsorption.
When any substance leaves the bloodstream and enters
the lumen of the kidney tubules, it is secretion.
By adjusting reabsorption and secretion, your body
adjusts its acid-base balance; if too many H+ ions were
kept in the plasma, there is too much acid, and the H+
ions will start to be secreted more.
74
Transport Maximum



When proteins are shuttling solutes, the rate of this shuttling has a
maximum, called a transport max (Tm).
If there are more solutes present than can be transported, the
solutes will end up in your urine. There will be a point at which you
can saturate these transporters. For instance, when your blood
glucose levels are elevated because you have a problem making
insulin or responding to insulin, then you will have an increase in
glucose load in Bowman’s capsule. This excess filtered load will
cause a spill of glucose into the urine.
After the PCT, there are no more glucose transporters to reabsorb
it. 320 is the max rate to filter glucose. If you filter 125 and
reabsorbed 125, how much did you excrete? None. If you filter 375
but reabsorb 320 (transport maximum), 55 is excreted
75
Threshold




Transport maximum is the total transport maximum
throughout all of the nephrons in the kidney. They do
not all have the exact number and type of transporters.
One single nephron might get to maximum and a tiny
amount of glucose will appear in the urine. As more
nephrons reach their maximum, more glucose will
appear in the urine.
That appearance of glucose in the urine before you
reach the overall Tm of the kidney is called threshold.
Threshold is the plasma concentration at which a
substance begins to appear in the urine
76
=solute
= transporter
1
5/min
2
3
4
5
Transport maximum is reached
when carriers are saturated.
77
=solute
Excretion
= transporter
1
5/min
2
3
4
5
Transport maximum is reached
when carriers are saturated.
78
Calculate Glucose Excretion





Step 1: Calculate their filtered load: GFR x
plasma glucose level 90 x 2
Step 2: Determine reabsorption of glucose
(maximum is 150).
Step 3: Subtract 150 from 180, and that tells
you their excretion.
Excretion = filtration – reabsorption
Answer 180 – 150 = 30 mg/min
79
A patient with uncontrolled diabetes has a
GFR of 90 ml/min, a plasma glucose of 2mg/ml, and a transport max
(Tm) shown in the figure. What is the glucose excretion for this
patient?
250
(mg/min)
200
Glucose
a. 0 mg/min
b. 30 mg/min
c. 60 mg/min
d. 90 mg/min
e. 120 mg/min
Transport
Maximum
(150 mg/min)
Reabsorbed
150
100
Excreted
.
50
Threshold
0
50 100
350
Filtered
150
200
Load of Glucose
(mg/min)
Copyright © 2006 by Elsevier, Inc.
250
300
80
Answer:
Excretion = filtration (GFR x Pglu) – reabsorption (Tmax)
180 – 150 = 30 mg/min
250
GFR = 90 ml/min
PGlu = 2 mg/ml
Tmax = 150 mg/min
(mg/min)
200
Glucose
a. 0 mg/min
b. 30 mg/min
c. 60 mg/min
d. 90 mg/min
e. 120 mg/min
Transport
Maximum
(150 mg/min)
Reabsorbed
150
100
Excreted
.
50
Threshold
0
50 100
350
150
200
250
300
Filtered Load of Glucose
Copyright © 2006 by Elsevier, Inc.
(mg/min)
81
A patient with uncontrolled diabetes has a
GFR of 90 ml/min, a plasma glucose of 2.33mg/ml, and a transport
max (Tm) shown in the figure. What is the glucose excretion for this
patient?
250
(mg/min)
200
Glucose
a. 0 mg/min
b. 30 mg/min
c. 60 mg/min
d. 90 mg/min
e. 120 mg/min
Transport
Maximum
(150 mg/min)
Reabsorbed
150
100
Excreted
.
50
Threshold
0
50 100
350
Filtered
150
200
Load of Glucose
(mg/min)
Copyright © 2006 by Elsevier, Inc.
250
300
82
Answer:
Excretion = filtration (GFR x Pglu) – reabsorption (Tmax)
210 – 150 = 60 mg/min
250
GFR = 90 ml/min
PGlu = 2.33 mg/ml
Tmax = 150 mg/min
(mg/min)
200
Glucose
a. 0 mg/min
b. 30 mg/min
c. 60 mg/min
d. 90 mg/min
e. 120 mg/min
Transport
Maximum
(150 mg/min)
Reabsorbed
150
100
Excreted
.
50
Threshold
0
50 100
350
150
200
250
300
Filtered Load of Glucose
Copyright © 2006 by Elsevier, Inc.
(mg/min)
83
Urea





Urea is also reabsorbed in the PCT.
This happens because its concentration in the tubule is high, so it
diffuses down its concentration gradient, which means it will leave
the tubule and enter the capillaries.
This is an advantage because it is a particle, and it brings water
with it.
But urea is a waste product…how will we get rid of it?
We will reabsorb it now and secrete it again further along in the
nephron. By the time the reabsorbed urea travels in the vasa recta
to the distal convoluted tubule, its concentration is higher in the
bloodstream than it is in the tubule, so it diffuses back out of the
capillaries and into the tubule to be excreted. The DCT is
impermeable to water, so water does not follow it.
84
Diuretics in the PCT


Lasix
Mannitol
cause diuresis by reducing net water
reabsorption from the proximal
convoluted tubule
 “Potassium sparing” refers to a diuretic’s
tendency to decrease potassium excretion

85
Diuresis in the PCT


Diuresis means the person is excreting a lot of water.
This is what happens in diabetes mellitus (and insipitus).
It makes the person thirsty, so they drink a lot of water.
However, that is not why they have diuresis.
 The reason for the diuresis is the large amount
of glucose in the tubule draws water with it,
since glucose is a particle.
 Thus, the large filtered load of glucose has an
osmotic effect on the tubule
86
Now we leave the PCT and
enter the Loop of Henle





Our kidneys are responsible for adjusting the urinary
output.
They are responsible for determining if you have a lot of
urine which very dilute, or scant, concentrated urine.
If you drink a lot of water, it will make your urine dilute
(more water than solutes).
If you are dehydrated, your urine will be concentrated
(more solutes than water).
Caffeine and alcohol are dehydrating, so they have the
opposite effect of drinking water. They block antidiuretic
hormone (ADH) too.
87
Before we move onto the Loop of Henle, be mindful
of the following:



How can you make a solution
more concentrated? Take out
water or add more solute.
How can you make a solution
less concentrated? Add water or
take out more solute.
Your kidneys play that game. To do
that, we have to separate solutes
and water. But how do we do that,
since water follows particles? There
are several parts of the nephron that
are impermeable to water.
88
LOOP OF HENLE:
Ascending Limb




Impermeable to water, so no water is
reabsorbed or secreted.
Permeable to NaCl and urea:
NaCl (or sodium and chloride separately)
diffuses out of tubule (reabsorbed)
Urea diffuses into tubule (secreted)
89
Saltiness in the LOH



Now let’s take the LOH together: on the descending limb we have
water leaving and salt entering the lumen.
On the ascending limb, we have salt leaving, and no more water
leaving the lumen.
As it goes up the ascending limb, it is becoming more and more
hypo-osmotic (less and less salty). At the top of the ascending limb,
it tastes less salty than blood plasma.
Now we leave the LOH and enter
the distal convoluted tubule
(DCT)
90
Distal Convoluted Tubule (DCT)




5% more sodium is reabsorbed
The DCT activity can be influenced by hormones.
If there are no hormones around, these cells don’t
do anything; whatever is remaining in the lumen
will go into the bladder.
If there are no hormones, the last 13% of water
and the last 3% of Na goes into the toilet.
Anti-diuretic hormone (ADH) and aldosterone will
cause more water and salt to be reabsorbed
(raises blood pressure).
91
Distal Convoluted Tubule (DCT)




Special cells in the DCT, called intercalated cells manage
your acid-base balance, to secrete more H+.
If you are in a state of acidosis (too much acid in your
blood) because you drank alcohol, your intercalated cells
will secrete more H+ to bring the pH back to normal.
If you are in a state of alkalosis because you have been
hyperventilating (breathing fast), will the intercalated
cells increase H+ reabsorption or H+ secretion?
Answer: increase H+ reabsorption.
92
Secretion



Secretion is the opposite of reabsorption. Any time you
see a solute going from the tubular cells and into the
lumen, it is called secretion. Secreted substances end
up in the urinary bladder.
It happens by active transport. We secrete acids, bases,
phosphates, excess potassium.
Secretion works this way: solutes diffuse out of the
peritubular capillary bed and into the tubular cells, then
they enter lumen of the convoluted tubule. From there,
they go out the collecting duct, and into the urinary
bladder.
93
Long-Term Dehydration

Compensations in a dehydrated person who is deprived
of water for 36 hours include the following:
 increased plasma renin
 increased plasma ADH
 decreased concentration of plasma atrial natriuretic
hormone (vasodilator made by the heart; increases
diuresis)
 increased water permeability of the collecting duct
 decreased water permeability in the ascending loop of
Henle
94
Hormones affecting the kidney







Renin: released by kidney when blood pressure is too low
ACE: Pulmonary capillary enzyme that responds to renin. When renin is
elevated, it cleaves angiotensin I into angiotensin 2.
Angiotensin II: causes blood vessel constriction to increase blood
pressure. It also stimulates the release of aldosterone.
Aldosterone: Secreted from the zona glomerulosa of the adrenal cortex.
It increases blood pressure by increasing sodium reabsorption. It is
primarily released due to elevated potassium levels.
ADH: Promotes aquaporin insertion in the cell membranes of the tubules
 Aquaporin is a protein that allows water to pass through the cell
membrane, to be absorbed out of the tubule.
Atrial natriuretic peptide (ANP): heart hormone that promotes more
diuresis and urine production to lower blood pressure.
Adenosine: Macula densa use this to molecule to change the radius of the
afferent arteriole.
95
Clinical Correlations





What are the symptoms of severe
dehydration?
1. Disoriented
2. Falls unconscious
3. Measurable loss of weight during
strenuous activity (water loss)
4. Blood pressure drops
96
Clinical Correlations







A marathon runner becomes dehydrated
during a race.
1. What will happen to their weight?
2. What will happen to blood volume?
3. What will happen to blood pressure?
4. What will happen to heart rate?
5. What will happen to their baroreceptors?
6. What will happen to sympathetic outflow?
97
Clinical Correlations







A marathon runner becomes dehydrated
during a race.
1. Weight goes down (water loss)
2. Blood volume decreases (water loss)
3. Blood pressure decreases (volume loss)
4. Heart rate increases (b/c of decreased BP)
5. Baroreceptors decrease firing (low BP)
6. Sympathetic outflow increases (to
98
compensate)
Clinical Correlations



A marathon runner becomes dehydrated
during a race.
1. What will happen to their Renal blood
flow (RBF)?
2. What will happen to their tubular load of
sodium?
99
Clinical Correlations


A marathon runner becomes dehydrated
during a race.
1. Renal blood flow (RBF) will decrease


The body does not want to lose more water
2. Tubular load of sodium will decrease

Sodium is reabsorbed so water will come with it
100
Clinical Correlations



A marathon runner becomes dehydrated
during a race.
1. What hormones would compensate for
this condition?
These would all be elevated:
Renin
 Angiotensin II
 Aldosterone
 ADH

101
Clinical Correlations


A marathon runner becomes dehydrated
during a race.
1. What will be the urinary output?


Low volume
2. What will be the urine concentration?

High concentration
102
Clinical Correlations


A marathon runner becomes dehydrated
during a race and falls unconscious.
1. What type of shock is this?


Hypovolemic shock
2. What is the treatment?

I.V. saline/bicarbonate solution
Giving saline will increase water retention
 Giving bicarbonate will reduce acidosis

103
Clinical Correlations


A marathon runner becomes dehydrated
during a race and falls unconscious.
1. Why do they have acidosis?
Hypovolemic shock reduces oxygen delivered to
tissues.
 Muscles without oxygen start to convert to
anaerobic metabolism to get their ATP. The
waste product of anaerobic metabolism is lactic
acid.
 The buildup of lactic acid without the kidney
104
excreting it causes metabolic acidosis.

Clinical Correlations




January 12th, 2007, A 28 year-old mother of three from
Sacramento decides to go on a radio program to compete
in a contest called, “Hold your Wee for a Wii.”
During this contest, contestants drank great volumes of
plain water. She drank 6 liters in 2 hours (2 liters an hour).
The maximum the kidney can filter is 1 liter an hour.
After the contest, she called her co-workers to say she
wasn’t coming to work because her head hurt so badly.
Later she is found dead.
105
Clinical Correlations



Drinking too much water changes the extracellular
osmolality. When the plasma is too dilute (too
much water, too few solutes), water will leave the
bloodstream to enter the tissues, where there are
more solutes (solutes SUCK!).
Water will enter the tissues (intracellular body fluid
compartment), including the brain.
The excess water will cause the brain to swell.
106
Water moves through
Compartments






Intracellular water (or other fluid) is the watery substance inside a cell.
Interstitial water (or other fluid) is the watery substance between cells.
Extracellular water (or other fluid) is the watery substance that is outside
of cells. Some of it may be interstitial, some may be in the blood, joints,
CSF, etc.
The concentration of individual solutes (glucose, sodium, potassium,
chloride) is different in intracellular fluid than it is in extracellular or
interstitial fluid, but the total osmolarity (concentration of all the
solutes combined) of the intracellular fluid, extracellular fluid,
and interstitial and is the same.
Water can move from one compartment to another. It can be drawn out
of the plasma to enter the interstitial compartment first, and then it may
enter the cells.
Water can also move from the cells to the interstitial compartment, then
into the bloodstream.
107
Water/Salt Imbalance Problems

Expansion: the body has retained too much water
Contraction: the body has too little water

Hypo-osmotic volume



Hyperosmotic volume


The water in the body has too much water, too few solutes
The water in the body has too little water, too many solutes
Isosmotic volume

The water in the body has the proper balance of water and solutes.
108
Water/Salt Imbalance Problems




Hypo-osmotic volume expansion
 Excessive water drinking; plasma osmolality is reduced from too much
water, not enough solutes (hypo-osmotic) and the extracellular fluid
(outside of cells) volume has increased (expansion).
Hypo-osmotic volume contraction
 Excessive sweating; the person has lost a lot of salt, but has lost some
water, too. They are dehydrated (contraction) and have low salt levels
(hypo-osmotic). The water in the body has low osmolality due to loss of the
salt.
Hyperosmotic volume expansion
 High salt intake; there is too many solutes, water is retained, so the
overall volume is increased (expansion), but there is a lot of salt, so
osmolality is increased (hyperosmotic).
Hyperosmotic volume contraction
 Dehydration; the person has lost a lot of water, so overall volume is
decreased (contraction). The salt level has not changed, so that means
109
more salt dissolved in less water (hyperosmotic).
Water/Salt Imbalance Problems


Isosmotic Volume Contraction
 Diarrhea; loss of water and solutes. Overall water/salt
balance is maintained (isosmotic), but person loses
overall volume (contraction).
Isosmotic Volume Expansion
 Salt Infusion; person receives an i.v. of normal saline
(isosmotic), and overall volume of body fluid
increases (expansion).
110
Hyperosmotic volume
contraction


There would be elevated protein
concentration but NO CHANGE in
hematocrit with this condition
Diabetes insipidus would cause this
condition
111
Hyperosmotic volume expansion


Conn’s disease would cause this condition
There would be decreased protein
concentration and hematocrit
112
Hypo-osmotic volume
contraction


Addison’s Disease would cause this
condition
There would be increased protein
concentration and hematocrit
113
Hypo-osmotic volume
expansion


Syndrome of inappropriate ADH would
cause this condition
There would be decreased protein
concentration but NO CHANGE in
hematocrit with this
114
Iso-osmotic volume
expansion



There would be decreased protein
concentration and hematocrit
Infusion of a 0.9g% saline solution would
cause this condition
In these conditions there would be NO
CHANGE in the intracellular volume
nor osmolality
115
Iso-osmotic volume
contraction



In these conditions there would be NO
CHANGE in the intracellular volume
nor osmolality
There would be increased protein
concentration and hematocrit
Diarrhea or burns would cause this
condition
116
Water Imbalance category
Condition
Disorder
Proteins
Hct
Drinking too much water
Low
Normal
or inappropriate ADH
Syndrome
Hypo-osmotic volume expansion
Excess water, low solutes
Hypo-osmotic volume contraction
Loss of water and salt
Addison's disease
High
High
Hyperosmotic volume expansion
High salt intake
Conn's disease
Low
Low
Hyperosmotic volume contraction
Loss of water, normal salt levels
Diabetes insipidis
High
Normal
Isosmotic volume expansion
Increase in normal saline
Normal saline iv
Low
Low
Isosmotic volume contraction
Loss of water and solutes, but water/salt is normal Diarrhea
High
High
117
Hyponatremia
(too little sodium in the blood)




Causes
excessive sweating
persistent diarrhea
overuse of diuretic drugs
118
Hypokalemia
(low potassium in the blood)

Causes
 Inadequate potassium intake (rare)
 Gastrointestinal loss (vomiting or diarrhea)
 Urinary loss
 Thiazide diuretics
 Alkalosis in the blood
 Disease states that cause high aldosterone levels
 Conn’s syndrome (hyperaldosteronism)
 Cushing's syndrome (excess cortisol binds to the
Na+/K+ pumps, so it acts like aldosterone).
119
Clinical Correlations






Addison’s Disease
Conn’s Disease
Diabetes Mellitus
Diabetes Insipidus
Cushing’s Disease
Know which of these diseases has
hypernatremia, hypokalemia, hypo or
hyperglycemia, etc.
120
Addison’s Disease





Chronic adrenal insufficiency (low
cortisol levels)
Hyponatremia
Hypoglycemia
Hyperkalemia
Possible death at times of extreme stress

Addisonian crisis: low blood pressure  coma
121
Conn’s Disease



This is hyperaldosteronism.
The person releases too much
aldosterone, which increases sodium
retention, so water follows, and
hypertension results.
Condition associated primarily with
hypertension and mild hypernatremia and
mild hypokalemia. No diabetogenic
(glucose) problems.
122
Diabetes Mellitus


Condition characterized by polyuria, glucosuria, polydipsia and
ketonuria.
 Polyuria (frequent urination)
 Glucosuria (glucose in urine)
 Polydipsia (thirsty)
 Ketonuria (ketones in the urine)
When insulin does not pull glucose into the body cells, it stays in
high levels in the blood (hyperglycemia) and spills out in the urine
(glucosuria). The body is starving, so it breaks down fat into fatty
acids for energy, and ketones are the waste product. In small
amounts, they are broken down in the liver, but in large amounts,
they build up in the blood (ketoacidosis: lowers blood pH) and spill
out into the urine (ketonuria). Starvation, fasting, prolonged
vomiting, high protein diets, and low carbohydrate diets also cause
this condition.
123
Diabetes Insipidus


Condition characterized by polyuria and
polydipsia, but not glucosuria.
This is more like a disease of water loss
(ADH is not produced).
124
Cushing’s Disease





Hypernatremia
 Caused by lack of water in the blood, like
dehydration.
Hypokalemia (low potassium)
Hyperglycemia (excess glucose)
Diabetes mellitus
Weight gain, particularly of the trunk and face with
sparing of the limbs (central obesity), moon face, buffalo
hump, and sometimes growth of facial hair.
125
K+
Na+
Glucose
Addison's
High
Low
Low
Conn's
Mild low Mild high Normal
Diabetes Mellitus
High
Low
High
Diabetes Insipidus
High
High
High
Cushing's
Low
High
High
BP
Low
High
Other
Possible death at times of extreme stress
Polyuria, glucosuria, polydipsia, ketonuria, ketoacidosis
Polyuria, polydipsia only
Diabetes (Polyuria, glucosuria, polydipsia, ketonuria), central obesity,
moon face, buffalo hump, facial hair in women
126
Renal Physiology
PART
THREE
Renal Acid-Base Balance
127
Acids are being created constantly through
metabolism
• Anaerobic respiration of glucose produces
lactic acid
• Fat metabolism yields organic acids and
ketone bodies
• Carbon dioxide is also an acid.
Excess acids and bases must be eliminated from
the body
gas
H2O + CO2
Lungs eliminate
carbon dioxide
aqueous
H2CO3
H+ + HCO3 Kidneys can remove
excess non-gas acids and
bases
Excessive Acids and Bases can cause pH
changes---denature proteins
• Normal pH of body fluids is 7.40
• Alkalosis (alkalemia) – arterial blood pH rises above 7.45
• Acidosis (acidemia) – arterial pH drops below 7.35
• Acidosis:
– too much acid
– Too little base
• Alkalosis
– Too much base
– Too little acid
Compensation for deviation
• Lungs (only if not a respiratory problem)
– If too much acid (low pH)—respiratory system
will ventilate more (remove CO2) and this will
raise pH back toward set point
– If too little acid (high pH)—respiratory will
ventilate less (trap CO2 in body) and this will
lower pH back toward set point
• Kidneys
– If too much acid (low pH)—intercalated cells will
secrete more acid into tubular lumen and make
NEW bicarbonate (more base) and raise pH back
to set point.
– If too little acid/excessive base (high pH)proximal convoluted cells will NOT reabsorb
filtered bicarbonate (base) and will eliminate it
from the body to lower pH back toward normal.
Acid-Base Balance

How would your ventilation change if you
had excessive acid?


You would hyperventilate
How would your ventilation change if you
had excessive alkalosis?

Your breathing would become shallow
How can the kidneys control acids
and bases?


Bicarbonate is filtered
and enters nephron at
Bowman’s capsule
Proximal convoluted
tubule

Can reabsorb all
bicarbonate (say, when you
need it to neutralize
excessive acids in body)
OR

Can reabsorb some or
NONE of the bicarbonate
(maybe you have too much
base in body and it needs
to be eliminated)
How can the kidneys control acids
and bases?


Acidosis
Intercalated cells



Secrete excessive
hydrogen
Secreted hydrogen
binds to buffers in the
lumen (ammonia and
phosphate bases)
Secretion of hydrogen
leads to formation of
bicarbonate
HPO4NH3
What would happen if the respiratory
system had a problem with ventilation?
Respiratory Acidosis and Alkalosis
Normal PCO2 fluctuates between 35 and 45 mmHg
• Respiratory Acidosis
(elevated CO2 greater than
45mmHg)
• Depression of respiratory centers
via narcotic, drugs, anesthetics
• CNS disease and depression,
trauma (brain damage)
• Interference with respiratory
muscles by disease, drugs, toxins
• Restrictive, obstructive lung
disease (pneumonia,
emphysema)
• Respiratory Alkalosis (less
than 35mmHg- lowered
CO2)
• Hyperventilation syndrome/
psychological (fear, pain)
• Overventilation on mechanical
respirator
• Ascent to high altitudes
• Fever
What if your metabolism changed?
• Metabolic acidosis
• Bicarbonate levels
below normal (22
mEq/L)
• Ingestion, infusion or
production of more
acids (alcohol)
• Salicylate overdose
(aspirin)
• Diarrhea (loss of
intestinal bicarbonate)
• Accumulation of lactic
acid in severe Diabetic
ketoacidosis
• starvation
•
•
Metabolic alkalosis
bicarbonate ion levels higher
(greater than 26mEq/L)
• Excessive loss of acids
due to ingestion,
infusion, or renal
reabsorption of bases
• Loss of gastric juice
during vomiting
• Intake of stomach
antacids
• Diuretic abuse (loss of
H+ ions)
• Severe potassium
depletion
• Steroid therapy
Compensation



If the kidneys are the problem, the
respiratory system can compensate.
If the kidneys are secreting too much
H+(which makes too much bicarbonate,
causing metabolic alkalosis), breathing will
become slower so that less CO2 (an acid)
is lost.
If the kidneys are reabsorbing too much
H+(metabolic acidosis), breathing will
become faster.
Compensation



If the respiratory system is the problem,
the kidneys can compensate.
If breathing is too rapid (too much CO2,
an acid, is lost, leaving the blood in
respiratory alkalosis), Kidneys respond by
reabsorbing more H+.
If breathing is too shallow (not enough
CO2 is lost, leaving the blood in respiratory
acidosis), Kidneys respond by secreting
more H+.
Summary
 Let’s
summarize so we can
apply this to clinical conditions!
 Acidosis
 Can
be metabolic or respiratory
 Alkalosis
•
Can be metabolic or respiratory
Acidosis

Acidosis is excessive blood acidity caused
by an overabundance of acid in the blood
or a loss of bicarbonate from the blood
(metabolic acidosis), or by a buildup of
carbon dioxide in the blood that results
from poor lung function or slow breathing
(respiratory acidosis).
Acidosis





Blood acidity increases when people ingest substances
that contain or produce acid or when the lungs do not
expel enough carbon dioxide.
People with metabolic acidosis have nausea, vomiting,
and fatigue and may breathe faster and deeper than
normal.
People with respiratory acidosis have headache and
confusion, and breathing may appear shallow, slow or
both.
Tests on blood samples show there is too much acid.
Doctors treat the cause of the acidosis.
Metabolic acidosis


Caused from a decrease in bicarbonate in
the blood because of ingestion of an acid
(aspirin, ethanol, or antifreeze) or too
many acidic waste products have built up
(such as from untreated diabetes mellitus
or eating too much protein that the
kidneys cannot keep up with excreting the
acid ), or it could be from loss of
bicarbonate from diarrhea.
Treatment is give i.v. of sodium
bicarbonate.
Respiratory acidosis


Caused from an increase in CO2 in the
blood because the lungs are
hypoventilating (seen in asthma, COPD,
and overuse of sedatives or narcotics such
as valium, heroin, or other drugs which
make you sleepy).
Treatment is to increase ventilation
(oxygen mask).
Respiratory acidosis




May have no symptoms but usually experience
headache, nausea, vomiting, and fatigue.
Breathing becomes deeper and slightly faster (as
the body tries to correct the acidosis by
expelling more carbon dioxide).
As the acidosis worsens, people begin to feel
extremely weak and drowsy and may feel
confused and increasingly nauseated.
Eventually, blood pressure can fall, leading to
shock, coma, and death.
Alkalosis

Alkalosis is excessive blood alkalinity
caused by an overabundance of
bicarbonate in the blood or a loss of acid
from the blood (metabolic alkalosis), or by
a low level of carbon dioxide in the blood
that results from rapid or deep breathing
(respiratory alkalosis).
Alkalosis




People may have irritability, muscle
twitching, or muscle cramps, or even
muscle spasms.
Blood is tested to diagnose alkalosis.
Metabolic alkalosis is treated by replacing
water and electrolytes.
Respiratory alkalosis is treated by slowing
breathing.
Metabolic alkalosis



Caused from an increase in bicarbonate in the
blood because of ingestion of excess antacid
(Tums), eating excess fruits (vegetarian diets
and fad diets*), loss of acid from vomiting, or
loss of potassium from diuretics.
Treatment is to give an anti-emetic if the
problem is from vomiting. If not, give an i.v. of
normal saline to increase the blood volume.
If potassium is also low, would have to add that
to the i.v.
Respiratory alkalosis


Caused from a decrease in CO2 in the
blood because the lungs are
hyperventilating (anxiety, but not
panting).
Treatment is to breathe into a paper bag
for a while.
Condition
pH
Resp
CO2
Bicarb
Compensating?
Resp acidosis
Low
Hypoventilating
High
High
Yes
Resp acidosis
Low
Hypoventilating
High
Low
No
Resp alkalosis
High
Hyperventilating
Low
Low
Yes
Resp alkalosis
High
Hyperventilating
Low
High
No
Metab acidosis
Low
Normal
Low
Low
Yes
Metab acidosis
Low
Normal
High
Low
No
Metab Alkalosis
High
Normal
High
high
Yes
Metab Alkalosis
High
Normal
Low
High
No