TOPIC 18

STRUCTURE of RESPIRATORY SYSTEM

Airways:

*Tunes that carry air between environment and alveoli (Fig. 16.2 & 16.3)

1. nasal passages

2. pharynx (throat)

3. trachea (windpipe); fairly rigid structure (made of cartilage)

a. larynx (voice box) at entrance to trachea

4. trachea splits into right and left bronchi, which enter right and left lung, respectively. Bronchi are fairly rigid (made of cartilage)

5. bronchi branch into bronchioles, which are smooth muscle instead of cartilage and so are flexible

TOPIC 18

STRUCTURE of RESPIRATORY SYSTEM

Alveoli:

*Location of gas exchange with blood (Fig. 16.2 & 16.3)

1. Clusters of thin walled, inflatable, grapelike sacs at the terminal branches of the bronchioles

2. Walls consist of single layer of Type I alveolar cells

3. Type II alveolar cells secrete pulmonary surfactant which reduces surface tension in alveoli and keeps lungs from collapsing

4. surrounded by pulmonary capillaries (16.5)

5. NOTE: thinness of walls of each alveolus, and huge surface area (75 m²) of all alveoli, greatly facilitates diffusion of gases

TOPIC 18

STRUCTURE of RESPIRATORY SYSTEM

Lungs and Chest Cavity:

(Fig. 16.2)

1. Two lungs, each supplied by one of the bronchi

2. Lungs composed of bronchi, bronchioles, and alveoli, plus lots of elastic connective tissue

3. Lungs are smaller than the thoracic cavity, but occupy most of it. Two factors keep lungs close to thoracic wall (Fig 16.8)

4. Rib cage provides bony protection for lungs and heart

5. Diaphragm forms the floor of the chest cavity

TOPIC 18

STRUCTURE of RESPIRATORY SYSTEM

Lungs and Chest Cavity:

intrapleural fluid

- "sticky" in the same way that water is sticky when it holds two thin glass microscope slides together.

- you can move the slides back and forth against each other, but it is difficult to pull them apart.

- likewise, the intrapleural fluid allows movement of lungs along chest wall, but keeps the lungs "stuck" to the chest wall

TOPIC 18

STRUCTURE of RESPIRATORY SYSTEM

Lungs and Chest Cavity:

intrapleural pressure & intra-alveolar pressure

- P_ip is 756 mm Hg and the P_alv is 760 mm Hg when equilibrated with atmospheric pressure.

- This transmural pressure gradient across the lung wall is crucial in expanding the lung to fill the chest cavity.

TOPIC 18

RESPIRATORY CYCLE

Pressure Considerations:

(Fig. 16.11, 16.12 & 16.13)

1. Air moves from a region of high pressure to low pressure; it flows down a pressure gradient.

2. Air flows in and out of the lungs by reversing pressure gradients between lungs and environment

3. Important pressures related to respiration

4. When you inhale, you increase volume in intrapleural cavity so intrapleural pressure decreases

TOPIC 18

RESPIRATORY CYCLE

Pressure Considerations:

atmospheric (barometric) pressure...

- pressure exerted by weight of air in atmosphere on objects on earth's surface.

- at sea level, it is 760 mm Hg

TOPIC 18

RESPIRATORY CYCLE

Pressure Considerations:

intra-alveolar pressure...

- sometimes called intrapulmonary pressure

- it is the pressure within the alveoli

- whenever intra-alveolar pressure does not equal atmospheric pressure, air will move down its pressure gradient until intra-alveolar pressure equals atmospheric pressure

TOPIC 18

RESPIRATORY CYCLE

Pressure Considerations:

intrapleural pressure...

- also called intrathoracic pressure

- the pressure exerted outside the lungs within the thoracic cavity.

- usually just less than intra-alveolar pressure and atmospheric pressure, averaging about 756 mm Hg.

- Because thoracic cavity is closed to the outside, air can not move down pressure gradient into thoracic cavity

- HIGH volume = LOW pressure

- LOW volume = HIGH pressure

TOPIC 18

RESPIRATORY CYCLE

Respiration works by...

- changing the volume of the chest cavity, which changes the volume of the lungs, which changes the pressure in the lungs, and then air moves along its pressure gradient

TOPIC 18

RESPIRATORY CYCLE

Before the start of inspiration (taking a breath)...

- respiratory muscles are relaxed, intra-alveolar pressure = atmospheric pressure, and no air is flowing

TOPIC 18

RESPIRATORY CYCLE

At onset of inspiration...

- inspiratory muscles (primarily the diaphragm) contract, which results in enlargement of the thoracic cavity

TOPIC 18

RESPIRATORY CYCLE

As the thoracic cavity enlarges...

- the lungs are forced to expand to fill the larger cavity.

- As the lungs enlarge, the intra-alveolar pressure drops because the same number of air molecules now occupy a larger lung volume.

- Because the intra-alveolar pressure is less than atmospheric pressure, air follows its pressure gradient and flows into the lungs until no furthur gradient exists (i.e. the intra-alveolar pressure again equals atmospheric pressure)

- THUS... lung expansion is NOT caused by the movement of air into the lungs; instead, air flows into the lungs because of the fall in intra-alveolar pressure brought about by lung expansion

TOPIC 18

RESPIRATORY CYCLE

Deeper inspirations...

- are accomplished by contracting inspiratory muscles more forcefully, and by using accessory inspiratory muscles to enlarge the chest cavity further

TOPIC 18

RESPIRATORY CYCLE

At the end of inspiration...

- the inspiratory muscles relax, the chest cavity returns to original size, and the lungs return to original size

- as they do so, the intra-alveolar pressure increases as the same number of air molecules now occupy a smaller volume

- the air in the lungs then moves down its pressure gradient and expiration occurs until intra-alveolar pressure equals atmospheric pressure

- although at rest expiration is a passive process, during exercise it is an active process and expiratory muscles (primarily abdominal muscles) contract to decrease the size of the chest cavity during expiration

TOPIC 18

AIRWAY RESISTANCE

(Fig. 16.14)

1. Similar to cardiovascular system, resistance plays a role in determining airflow rates. An increase in airway radius decreases resistance and increases airflow rate. A decrease in airway radius increases resistance and decreases airflow rate.

2. Parasympathetic stimulation causes bronchoconstriction

3. Sympathetic stimulation causes bronchodilation

a. Useful in fight or flight

b. Useful in clinical treatments: administration of epi in a person with bronchial spasms can alleviate the problem

TOPIC 18

AIRWAY RESISTANCE

Matching blood flow and air flow:

*Need to have a good match between air flow and blood flow in the alveoli to avoid buildup of CO₂ or lack of O₂

1. Large Blood Flow & Small Airflow

a. too much CO₂ in alveolus, too little O₂ for blood to pick up

b. Local Control: the buildup of CO₂ and lack of O₂ cause

- vasodilation to increase blood flow

- bronchoconstriction to decrease airflow

TOPIC 18

VOLUME, CAPACITY, & VENTILATION

Important volumes (given for healthy young males)...

1. Max air that lungs can hold: 5700 mL (4200 mL in females)

2. Air still in lungs after normal expiration at rest: 2200 mL

3. Air in lungs after normal inspiration: 2700 mL

4. Tidal volume (volume of air entering/leaving in a breath): 500 mL

5. Air still in lungs after MAXIMAL expiration: 1200 mL

TOPIC 18

VOLUME, CAPACITY, & VENTILATION

Ventilation...

1. Pulmonary ventilation = tidal volume x respiratory rate

2. Resting conditions:

a. 500 mL/breath x 12 breaths/min = 6000 mL/min

3. Anatomical Dead Space: only air that reaches the alveoli is available for gas exchange; the air that stays in conducting airways is useless for gas exchange. This volume, called anatomical dead space, is about 150 mL

a. This means that of the 500 mL of air inspired per breath, only 350 mL is actually used for gas exchange

4. So, what's really important is alveolar ventilation

a. alveolar ventilation = (tidal volume - dead space) x respiratory rate

b. (500 mL/breath - 150 mL dead space) x 12 breath/min = 4200 mL/min

5. Slower deep breaths vs. Rapid shallow breaths

a. Table 16.1 --> MEMORIZE!!! (understand how to calculate the #'s on the graph)

b. Deep breaths are more effective than rapid shallow breaths

TOPIC 18

CONTROL of RESPIRATION: RHYTHMIC BREATHING PATTERN

Cardiac vs. Respiratory Systems

1. Recall that the heart is autothythmic, and that input from the nervous system is only required to modify the rate and strength of cardiac contraction. This is NOT the case in the lungs; CNS input is REQUIRED for breathing to occur at all

TOPIC 18

CONTROL of RESPIRATION: RHYTHMIC BREATHING PATTERN

Area of Brain Involved in Control of Rhythmic Breathing

1. Brain Stem:

a. Medullary respiratory center is responsible for

- basic rhythm of inspiration

- origin of nerves that supply the inspiratory muscles for normal breathing

- origin of nerves that supply inspiratory and expiratory muscles used for high rates of ventilation

b. apneustic and penumotaxic centers in pons of brain stem are postive and negative systems that finely regulate action potentials in inspiratory neurons to ensure smooth breathing

TOPIC 18

CONTROL of RESPIRATION: RHYTHMIC BREATHING PATTERN

Voluntary Control

1. Voluntary control of breathing is accomplished by the cerebral cortex which sends impulses directly to the motor neurons in the spinal cord that supply the respiratory muscles

TOPIC 19

OVERVIEW of RESPIRATION

External Respiration

(Fig. 16.1)

*Entire sequence of events involved in the exchange of O₂ and CO₂ between the external environment and the cells of the body.

1. VENTILATION: exchange of air between environment and lung air sacs (alveoli)

2. O₂ and CO₂ exchanged between alveoli and blood

3. O₂ and CO₂ are transported by blood between lungs and tissue

4. Exchange of O₂ and CO₂ between blood and tissues across capillaries

TOPIC 19

OVERVIEW of RESPIRATION

Internal Respiration

(Fig. 16.1)

*Intracellular metabolic processes which use O₂ and produce CO₂ and derive energy from nutrient molecules

TOPIC 19

OVERVIEW of RESPIRATION

Additional Functions of Respiratory System

(Fig. 16.1)

1. route for water loss and heat elimination

2. enhances venous return

3. helps maintian acid base balance

4. enables vocalizaiton

5. defends against inhaled pathogens

6. removes and modifies materials passing through pulmonary circulation

TOPIC 19

GAS EXCHANGE

Physical Principles

1. gas flows down its pressure gradient

2. every gas (such as oxygen) in a mixture of gases (such as air) has a partial pressure which is the relevant variable determining pressure gradients for a specific gas

TOPIC 19

GAS EXCHANGE

Physical Principles:

partial pressure of oxygen (P_O2) in dry atmospheric air at sea level...

1. atmospheric pressure = 760 mm Hg

2. oxygen makes up 21% of air

3. partial pressure of oxygen:

0.21 x 760 mm Hg = 160 mm Hg

TOPIC 19

GAS EXCHANGE

Physical Principles:

partial pressure of oxygen in alveoli is...

1. 100 mm Hg; this is fairly constant

2. less than 160 mm Hg because

a. water vapor, which exerts a partial pressure of 47 mm Hg, reduces P_O2 to 150 mm Hg

b. mixing of fresh inspired air with "old" air in lungs (lungs always have at least 1200 mL of air in them, even after max exhalation) further drops P_O2 to 100 mm Hg

TOPIC 19

GAS EXCHANGE

Physical Principles:

partial pressure of carbon dioxide (P_O2)...

1. 0.3 mm Hg in dry air

2. 40 mm Hg in alveoli because of CO₂ produced by tissues and brought to lungs by blood; this is fairly constant

TOPIC 19

GAS EXCHANGE

Oxygen:

pulmonary capillaries

1. P_O2 in alveoli is 100 mm Hg; in returning ("deoxygenated") blood of systemic circulation, it is usually about 40 mm Hg

2. Hence a pressure gradient of 60 mm Hg exists, toward blood from alveoli, so O₂ diffuses from alveoli into blood

TOPIC 19

GAS EXCHANGE

Oxygen:

systemic capillaries

1. P_O2 in blood (after oxygenated in lungs) is 100 mm Hg (ie. just what it is in the alveoli); in tissue, P_O2 is 40 mm Hg (although this varies quite a bit depending on amount of cellular metabolism)

2. Pressure gradient of 60 mm Hg exists, toward tissues from blood, so O₂ diffuses from blood to tissues

TOPIC 19

GAS EXCHANGE

Carbion Dioxide:

pulmonary capillaries (Fig. 17.4)

1. P_CO2 in alveoli is 40 mm Hg; in returning ("deoxygenated") blood of systemic circulation, it is usally about 46 mm Hg

2. Pressure gradient of 6 mm Hg exists, toward alveoli from blood, so CO₂ diffuses form blood into alveoli

TOPIC 19

GAS EXCHANGE

Carbion Dioxide:

systemic capillaries (Fig. 17.4)

1. P_CO2 in blood (after visit to lungs) is 40 mm Hg (ie. just what it is in the alveoli); in tissue, P_CO2 is about 46 mm Hg (although this varies quite a bit depending on amount of cellular metabolism)

2. Pressure gradient of 6 mm Hg exists, toward blood from tissues, so CO₂ diffuses from tissues to blood

TOPIC 19

GAS TRANSPORT: ROLE of HEMOGLOBIN (Hb)

Oxygen-Hb binding:

1. Each Hb molecule can bind up to 4 O₂ molecules; when it is carrying 4 oxygens, it is said to be fully saturated

2. Percent Hb saturation is a measure of the extent to which the Hb present is combined with oxygen, and can vary from 0 to 100%

3. The saturation of Hb with oxygen depends on the P_O2 of the blood; note that oxygen already boung to Hb does NOT contribute to P_O2!!!

4. The amount of O₂ bound to Hb depends on the P_O2.

TOPIC 19

GAS TRANSPORT: ROLE of HEMOGLOBIN (Hb)

Oxygen-Hb binding:

Relationship btwn. P_O2 and % Hb saturation is complex (Fig. 17.8)

1. In Pulmonary Capillaries, P_O2 is about 100 mm Hg; a large change in P_O2 here results in only a small change in % Hb saturation. Hence P_O2 can fall nearly 40% in lungs, but Hb still highly saturated. This facilitates loading of Hb with oxygen in lungs.

2. In Systemic Capillaries, P_O2 is about 40 mm Hg; a small change in P_O2 here results in a large change in % Hb saturated. Hence when P_O2 falls even a little in systemic capillaries, a large amount of O₂ disassociates from Hb. This facilitates unloading of O₂ from Hb in tissues

3. Bottom Line: Hb acts as oxygen storage location in the blood, ...

allowing the blood to carry much more oxygen than it could otherwise. As oxygen diffuses from the alveoli into the blood, it is loaded by Hb very rapidly; this loaded oxygen does not contribute to the blood P_O2, so more oxygen enters the blood and is picked up by Hb, and so on. As oxygen diffuses from the blood into the tissues, oxygen unloads from the Hb into the blood, where it continues to diffuse into the tissues.

TOPIC 19

GAS TRANSPORT: ROLE of HEMOGLOBIN (Hb)

Oxygen-Hb binding:

modificaiton of O₂-Hb binding curve (Fig. 17.9-17.10)

1. Increased metabolism leads to increase in tissue temperature, acidity, CO₂, and 2-3 diphosphoglycerate (a metabolite produced by RBC's). An increase in all these variables "right shifts" the O₂-Hb curve, which results in more unloading of oxygen for a given P_O2 (ie. Hb delivers more O₂ to the tissues at lower P_O2).

NOTE: this is known as the "Bohr Effect" when caused by increases in CO₂ and acid.

2. CARBON MONOXIDE: "left shifts" the O₂-Hb curve, so that less oxygen is delivered to tissues for a given level of P_O2. In addition, Hb binds CO 240 times more readily than it does O₂. These factors result in rapid death when breathing CO.

TOPIC 19

GAS TRANSPORT: ROLE of HEMOGLOBIN (Hb)

Carbon Dioxide Transported in the Blood in 3 Ways:

dissolved in blood (Fig. 17.11)

1. about 10% of CO₂ transported this way

2. dependent on P_CO2

TOPIC 19

GAS TRANSPORT: ROLE of HEMOGLOBIN (Hb)

Carbon Dioxide Transported in the Blood in 3 Ways:

Bound to Hb (Fig. 17.11)

1. about 30% of CO₂ bound to globin portion of Hb (not heme portion as O₂ does)

2. reduced Hb (ie. unoxygenated) has a greater affinity for CO₂ than does oxygenated Hb, which facilitates Hb picking up CO₂ in tissue capillaries

TOPIC 19

GAS TRANSPORT: ROLE of HEMOGLOBIN (Hb)

Carbon Dioxide Transported in the Blood in 3 Ways:

as bicarbonate (Fig. 17.11)

(HCO₃^-)

1. 60% of CO₂ converted to HCO₃^- and H⁺ by the enzyme carbonic anhydrase within RBC's (this RXN uses water also)

2. HCO₃^- then diffuses out of the RBC's, and Cl^- diffuses into the RBC's to restore the elecrical gradient. This is called the chloride shift.

3. The H⁺ remaining in the RBC's binds to Hb; again, deoxygenated Hb has a greater affinity for H⁺ than does oxygenated Hb. This helps buffer the blood, in that if the H⁺ left in the RBC's were to diffuse into the plasma, it would greatly increase the acidity of the blood.

4. The fact that removal of O₂ from Hb increases the ability of Hb to pick up CO₂ and CO₂ generated H⁺ is known as the Haldane Effect.

5. These RXN's are reverse once the blood reaches the pulmonary capillaries, and CO₂ leaves the blood and enters the alveoli

TOPIC 19

CONTROL of RESPIRATION: REGULATION of MAGNITUDE of VENTILAITON

Overview

P_O2 and P_CO2 in the blood leaving the lungs are kept fairly constant; both of these variables, plus H⁺, are monitored and regulated

TOPIC 19

CONTROL of RESPIRATION: REGULATION of MAGNITUDE of VENTILAITON

Role of Decreased Arterial P_O2 in Regulating Ventilation

(Fig. 17.18)

1. Arterial P_O2 in monitored by peripheral chemoreceptors in the carotid arteries and aortic arch

2. These chemoreceptors are not sensitive to changes in P_O2 from 100 mm Hg to 60 mm Hg; ie. P_O2 can drop 40% before they will cause an increase in ventilation

a. Not that critical; recall that Hb is still 90% saturated at P_O2 of 60 mm Hg.

3. Interesting Note: these chemoreceptors monitor P_O2, NOT O₂ that is bound to Hb. Thus if you suffer from anemia, and so you don't have enough Hb to carry O₂, the chemoreceptors do not "notice" the problem, and ventilation is not increased!

TOPIC 19

CONTROL of RESPIRATION: REGULATION of MAGNITUDE of VENTILAITON

Role of Increased Arterial P_CO2 in Regulating Ventilation

(Fig. 17.20)

1. Central chemoreceptors in the medulla monitor P_CO2 precisely

2. An increase in P_CO2 results in more CO₂ crossing blood brain barrier in medulla. AFTER CO₂ has crossed the blood brain barrier, the CO₂ reacts with water to form bicarbonate and H⁺; it is the increase in H⁺ in the ECF of the medulla which is detected by the central chemoreceptors. They cause an increase in ventilation to blow off excess CO₂ (and thereby bring in additional O₂)

3. This system fails at very high levels of P_CO2 (above 80 mm Hg). Such high levels depress brain function and depress respiration, and lead to death.

TOPIC 19

CONTROL of RESPIRATION: REGULATION of MAGNITUDE of VENTILAITON

Role of Increased Arterial H⁺ in Regulating Ventilation

(Fig. 17.18)

1. H⁺ cannot cross the blood brain barrier, so the increase in blood H⁺ that accompanies an increase in blood P_CO2 does not affect central chemoreceptors.

2. The peripheral chemoreceptors are sensitive to changes in blood H⁺, and cause changes in ventilation accordingly. However, this response is minor compared to the response in the central chemoreceptors caused by CO₂.

3. However, changes in blood H⁺ caused by factors other than increased CO₂ (e.g. by diabetes) does cause a response in the peripheral chemoreceptors that changes ventilation. This is one mechanism of acid/base balance in the body, as we'll see later.

TOPIC 20

URINARY SYSTEM

Overview:

Function of Urinary System

1. Urine = modified blood plasma (main component)

2. Maintiain water balance in the body

3. Regulating quantity and concentration of most ECF ions (don't forget that the ECF is composed of both blood plasma and interstitial fluid) such as Na+, Cl-, K+, and HCO3-

4. Maintaining plasma volume

5. Maintaining acid-base balance

6. Maintaining proper osmolarity of body fluids

7. Excreting end products of bodily metabolism (e.g. urea, uric acid)

8. Excreting foreign compounds (e.g. drugs, pesticides, food additives)

9. Secreting erythropoietin (hormone that stimulates RBC production)

10. Secreting renin ( hormone involved in salt regulation)

11. Converting vitamin D to its active form

TOPIC 20

URINARY SYSTEM

Overview:

Major Components of Urinary System

(Fig. 18.1 & 18.2)

1. Kidneys

a. 2 bean shaped kidneys that lie in back of abdominal cavity

b. Produce urine from blood plasma

2. Renal artery: brings blood to the kidney

3. Renal vein: takes blood away from kidney

4. Renal pelvis: urine collecting cavity in inner core of each kidney

5. Ureter: carries urine from each renal pelvis to bladder

6. Urinary bladder: temporary urine storage area

7. Urethra: tube from bladder to environment for elimination of urine

TOPIC 20

URINARY SYSTEM

Overview:

Kidney Structure (Fig. 18.2)

1. each kidney composed of approx. 1 million microscopic functional units called nephrons

2. arrangements of nephrons give rise to two distinct regions

a. Outer Region: renal cortex

b. Inner Region: renal medulla

TOPIC 20

URINARY SYSTEM

Overview:

Nephron Structure (Fig. 18.6)...

vascular component

*Bring blood to and from the nephron

*Cortex Region

1. RENAL ARTERY enters kidney then subdivides

2. into AFFERENT ARTERIOLES, one of which supplies each nephron, and subdivide

3. into GLOMERULAR CAPILLARIES. The GLOMERULUS of each nephron is a ball-like tuft of these capillaries, and is where FILTRATION occurs. The glomerular capillaries join together to form...

4. the EFFERENT ARTERIOLE, which leaves the glomerulus. This arteriole carries blood that was not filtered in the glomerulus, and which has not yet exchanted materials with the surrounding tissue. This is the ONLY place in the body where an arteriole LEAVE capillaries. The efferent arteriole quickly subdivides into...

5. the PERITUBULAR CAPILLARIES, which supply the renal tissue with blood, and are important in exchanges between the tubular system and the blood during urine production. They completely surround the tubular components.

TOPIC 20

URINARY SYSTEM

Overview:

Nephron Structure (Fig. 18.3)...

tubular component

*Where urine is made

*Medulla region

1. Hollow fluid filled tube formed by a single layer of epithelial cells. Even though it is continuous, it is arbitraily divided into different segments based on differences in structure and function along its length

2. BOWMAN'S CAPSULE begins the tubular component, and is a doubled wall cup that surrounds the glomerulus and collects the fluid filtered from the glomerular capillaries. From there, filtered fluid passes into...

3. the PROXIMAL TUBULE, which is highly coiled and lies entirely within the cortex.

4. Next is the LOOP OF HENLE, which from the U-shaped loop that dips into the renal medulla. The DESCENDING LIMB goes from the cortex into the medulla; the ASCENDING LIMB goes back up into the cortex from the medulla, and returns to the glomerular region of its own nephron.

5. The JUXTAGLOMERULAR APPARATUS lies next to the glomerulus, is composed of both tubular and vascular components, and is involved in regulating kidney function. Beyond this...

6. the DISTAL TUBULE, which is highly coiled and lies entirely within the cortex. This empties into a...

7. COLLECTING DUCT, eahc of which collects fluid from up to 8 nephrons.

TOPIC 20

URINARY SYSTEM

Overview:

The Three Basic Renal Processes (Fig. 18.7)

glomerular filtration

1. blood flows through the glomerulus

2. about 20% of plasma that enters is filtered into the Bowman's capsule, and enters the tubular system

3. all blood components (except proteins and RBC's) are non-selectively filtered along with plasma at this step into the tubular system

4. on average, approx. 180 liters (47.5 gallons) of glomerular filtrate fromed per day

TOPIC 20

URINARY SYSTEM

Overview:

The Three Basic Renal Processes (Fig. 18.7)

tubular reabsorption

1. As filtrate flows through tubules, substances of value to the body are returned to the peritubular capillaries and so re-enter the circulatory system

2. of the 180 liters of filtrate produced per day, about 178.5 liters are reabsorbed in this process; the other 1.5 liters ultimately is eliminated as urine

TOPIC 20

URINARY SYSTEM

Overview:

The Three Basic Renal Processes (Fig. 18.7)

tubular secretion

1. selective transfer of substances from peritubular capillary INTO the tubular system.

2. the 80% of the blood that is NOT filtered into Bowman's capsule this can have selected components removed by this process; in general this is a rapid way to remove specific substances from the blood.

TOPIC 20

URINARY SYSTEM

Overview:

Important Notes

1. Don' forget that there is free exchange between the plasma and teh interstitial fluid in the capillaries and lymph in the whole body, so ALL THE ECF IS FILTERED THROUGH THE KIDNEYS. Thus by performing their regulatory and excretory roles on the plasma, the kidneys maintain the proper interstitial fluid environment for optimal cell funciton.

2. At rest, 20% to 25% of the blood volume is pumped to the kidneys, i.e. nearly a quarter of your blood is going to get "cleansed" at any given moment

TOPIC 20

URINARY SYSTEM: GLOMERULAR FILTRATION

Process of Filtration

1. Glomerular membrane allows NONSPECIFIC passage of plasma and plasma ions from vascular system into tubular system; note that the glomerular capillary walls (which are part of the glomerular membrane) are 100 times more permeable to water and small solutes than normal capillary walls.

2. Glomerular membrane excludes >99% of all proteins in blood from tubular system

3. Glomerular Filtration Rate (GFR) is the rate at which plasma is filtered into tubular system from vascular system

4. Filtration rate is determined by:

a. surface area of glomerular membrane

b. permeability of glomerular membrane

c. glomerular capillary blood pressure

d. hydrostatic pressure (cannot be regulated)

e. plasma osmotic pressure (cannot be regulated)

5. GFR is about 125 ml/min for males for both kidneys

6. GFR is about 115 ml/min for females for both kidneys

TOPIC 20

URINARY SYSTEM: GLOMERULAR FILTRATION

The Problem of GFR and Blood Pressure

(Fig. 18.10)

1. Challenge: GFR is directly determined by the blood pressure in the glomerular capillaries: the higher the bp the higher teh GFR. BUT you don't want changes in arterial bp changing the GFR.

Think about exercise: you don't want increase in bp caused by exercise to increase GFR and hence urine output

2. Solution: The kidneys are able to regulate the blood pressure in the glomerular capillaries as long as mean arterial blood pressure does not go below 80 or above 180 mm Hg.

TOPIC 20

URINARY SYSTEM: GLOMERULAR FILTRATION

Intrinsic Regulation of GFR via Glomerular Capillary BP

1. Myogenic properties of the arterioles in the kidney AND the juxtaglomerular apparatus in the kidney automatically detect changes in bp and adjust the GFR accordingly.

- For Example: when you start exercising and your overall bp goes up, these two mechanisms REDUCE bp in the glomerular capillaries by vasoconstricting the arterioles that lead to them, so that GFR goes back to normal. Likewise if your bp goes down these two mechanisms cause vasodilation of the blood vessels to increase the GFR

TOPIC 20

URINARY SYSTEM: GLOMERULAR FILTRATION

Extrinsic Regulation of GFR via Glomerular Capillary BP

1. Occurs when mean arterial pressure outside the 80 to 180 mm Hg

2. Recall the baroreceptor reflex response from Topic 18: baroreceptors sense changes in mean arterial blood pressure, which ultimately leads to stimulation of automatic nervous system to either vasoconstrict or vasodilate blood vessels in the body

3. Drop in BP (excess sweating, bleeding): Sympathetic activity increases, causes vasoconstriction in most arterioles in body in increase total peripheral resistance as compensation (Fig. 18.12)

a. Afferent arterioles to the glomeruli vasoconstrict, which reduces glomerular filtration, and hence reduces urine output. This results in an increase in blood plasma volume, which helps increase mean arterial blood pressure.

4. Increase in BP: Sympathetic activity REDUCED, which results in vasodilation of most arterioles in body to decrease total peripheral resistance

a. Afferent arterioles to the glomeruli vasodilate, glomerular filtration increases so urine output increases, which reduces plasma volume and mean arterial BP

5. GFR can also be regulated via surface area and permeability changes in the glomerular membrane but this process is not well understood.

TOPIC 21

TUBULAR REABSORPTION

Introduction:

1. Highly selective process

a. Need to get essential materials out of tubules and back in blood

b. Most wastes, other than urea, are too big to be reabsorbed, and so are excreted in the urine

2. Examples of Reabsorption Rates (Table 18.1)

a. 99% of filtered water (47 gallons/day)

b. 100% of filtered sugar (2.5 pounds/day)

c. 99.5% of filtered salt (0.36 pounds/day)

TOPIC 21

TUBULAR REABSORPTION

Process of Reabsorption: Transepithelial Transport

1. Reabsorption requires molecules to cross two membranes: apical membrane and basolateral membrane (Fig. 18.13)

2. Two types of reabsorption (Fig. 18.14)

a. ACTIVE: at least one of the steps requires energy

b. PASSIVE: none of the steps requires energy

TOPIC 21

TUBULAR REABSORPTION

Reabsorption of Na⁺ (Fig. 19.13a)

1. 99.5% of filtered Na⁺ is reabsorbed

2. Na⁺ uses facilitated diffusion to cross apical membrane

3. Crosses basolateral membrane using the Na⁺- K⁺- ATPase pump which moves Na+ against concentration gradient from tububar cell into interstitial fluid; then it passively diffuses into blood

4. Low plasma Na+ causes release of hormone ALDOSTERONE which causes increased reabsorption of Na+ by causing existing channels to open and stimulating synthesis of new channels and new Na⁺- K⁺- ATPase pumps 

TOPIC 21

TUBULAR REABSORPTION

Reabsorption of Substances via Na⁺ Dependent Secondary Active Transport

(Fig. 19.13a & 18.15)

1. Glucose and amino acids and other nutritionally important compounds are moved against their concentration gradients by secondary active transport

2. These substances are co-transported across apical membrane along with the Na+ and then diffuse across basolateral membrane

3. NOTE that if is actually teh Na⁺- K⁺- ATPase pump in the basolateral membrane that drives this process by keeping the concentration of Na+ low in the tubular cell so that a concentration gradient exists from tubular lumen into tubular cell

4. So they get a free ride with the Na+; if no Na+, the pump shuts down and nothing is transported by secondary mechanisms.

5. Glucose reabsorption: (Fig. 18.15)

a. The maximum transport rate for glucose is approx. 125 mg/min

b. Under normal conditions, approx. 125 mg/ml is reabsorbed

c. If you have more than 375 mg/min that is available for reabsorption, the excess ends up in the urine

- People with diabetes mellitus have high levels of plasma glucose, and end up excreting a lot of glucose in the urine because it all can not be reabsorbed

Bottom Line: Kidneys do NOT regulate plasma glucose over a wide range of values, from essentially 0 to 3 times the normal amount of blood glucose, i.e. if you have extra glucose up to 3 times the normal amount, your body holds onto it.

TOPIC 21

TUBULAR REABSORPTION

Reabsorption of Substances via Na⁺ Dependent Passive Processes

1. CHLORIDE IONS (Cl^-) (Fig. 19.13a): passively follow the electrical gradient of Na+

2. Water molecules (in Proximal Tubules ONLY; see below for water reabsorption in distal tubules):

osmotically follow Na+ across the membrane from proximal tubules to interstitial fluid (Fig. 18.14b)

3. Urea reabsorption (in Proximal Tubules ONLY; see below for urea reabsorption in distal tubules)

follows concentration gradient established by water leaving the tubules (Fig. 19.5)

a. Water leaves tubules, which increases tubular concentration of urea relative to the interstitial concentration, so it flows down its concentration gradient into the interstitial fluid.

b. Although half of urea is reabsorbed, the other half is excreted, which in humans works just fine.

c. NOTE: urea build up due to renal failure is only mildly toxic compared to build up of H+ and K+

TOPIC 21

TUBULAR REABSORPTION

Reabsorption of Phosphate (also true for Ca⁺⁺ and some other electrolytes):

1. The normal reabsorption rate of phosphate equals normal plasma concentration of phosphate

2. If you ingest excess phosphate above normal plasma concentration, the excess is not reabsorbed and so is excreted in the urine= very tight regulation compared to glucose

3. Parathyroid hormone can alter the reabsorption rates of electrolytes to conserve them if need be

TOPIC 21

TUBULAR SECRETION

General:

1. Supplemental mechanism to filtration to get rid of substances

2. Essentially is the reverse of tubular reabsorption

TOPIC 21

TUBULAR SECRETION

Secretion of H⁺

1. When ECF is too acidic (i.e. too much H+), H+ is secreted passively (i.e. moves by diffusion from peritubular capillaries to tubular system)

TOPIC 21

TUBULAR SECRETION

Secretion of K⁺

(Fig. 19.19)

1. K+ must be closely regulated:

-if K+ too low in ECF= hyperpolarization of nerve and muscle cell membranes (=reduced excitability)

- high K+ in ECF increases membrane excitability, especially in the heart, which can leand to cardiac arrhythmias

2. K+ actively moved in opposite directions by reabsorption in the proximal tubule and secretion in the distal tubule

3. The active transport of Na+ during Na+ reabsorption results in the secretion of K+, because Na⁺- K⁺- ATPase pump moves Na+ and K+ in opposite directions

4. K+ secretion, not K+ filtration or reabsorption, is the process regulated by the kidneys to maintain proper amounts of K+

a. If Plasma K+ is too high:

- The increased plasma K+ directly increases ALDOSTERONE production, which increases K+ secretion and hence excretion in the urine

b. If plasma K+ is too low:

- Aldosterone production reduced, so secretion of K+ is decreased = less K+ in the urine

5. Problems with K+ secretion:

a. Because low plasma Na+ also stimulates aldosterone production to increase Na+ reabsorption, conservation of Na+ can inadvertently eliminate K+ via the aldosterone mechanism

b. K+ secretion is also inversely related to H+ secretion, so if H+ secretion is increased under high acid concentrations, that can result in an inadvertent increase in K+

TOPIC 21

TUBULAR SECRETION

Water Ions:

1. Separate secretory carriers for waste ions

2. Involved in removal of:

a. unwanted endogenous substance, such as prostaglandins

b. foreign inorganic chemicals, such as presticides and drugs

- NOTE that the liver ionizes many foreign substances so they can be eliminated by this process in the kidneys

3. Secretion of waste ions not regulated; basically as many of these substances as possible are secreted and eliminated in urine

TOPIC 21

URINE CONCENTRATION

(Fig. 19.7)

Overview:

Need to be able to produce urine of varying concentrations

1. If you have consumed a lot of water, you need to be able to produce dilute urine so that you don't lose too many ions

2. If you have been sweating a lot, you need to conserve water and so produce concentrated urine

3. The way this is accomplished is by:

a. Using loop of Henle to maintain a concentration gradient within the interstitial fluid of the renal medulla;

b. Passing the collecting tubule through this concentration gradient

c. The collecting tubule is selective permeably to water.

d. If you need to conserve water, the collecting tubule is made permeable to water so water leaves the collecting tubule and is removed from the urine.

e. If you need to eliminate water, the collecting tubule is made impermeable to water, and all the water in the collecting tubule ends up in the urine.

f. You must look at Figure 19.7 to see how this works!

TOPIC 21

URINE CONCENTRATION

(Fig. 19.7)

Overview:

Need to be able to produce urine of varying concentrations

TOPIC 21

URINE CONCENTRATION

(Fig. 19.7)

Countercurrent Multiplication

1. The descending loop of Henle is permeable to water, and does not transport Na+

2. The ascending loop of Henle is not permeable to water, but has active Na+ transport systems that can pump out Na+ against an osmotic pressure of 200 mosm/liter.

3. Na+ is pumped out of the ascending loop, which increases the osmolarity of the interstitial fluid, which causes water to leave the descending loop.

4. The water leaving the descending loop causes the fluid in the loop to increase in osmotic pressure

5. Net Result: the fluid leaving the loop has an osmotic pressure of 100, and a interstitial fluid of the renal medulla

TOPIC 21

URINE CONCENTRATION

(Fig. 19.7)

Controlling Urine Concentration (Fig. 19.9)

1. The collecting tubule runs through the concentration gradient as it heads toward renal pelvis

2. The distal and collecting tubules are impermeable to water, so the urine is hypotonic with an osmotic pressure of 100 mosm/liter. HOWEVER, in the presence of vasopressin (used to be called Anti-Diuretic Hormone) the distal and collecting tubules become permeable to water; the more vasopressin present, the more permeable these tubules become to water

3. Vasopressin is produced by the hypothalamus, and stored in the posterior pituitary; the hypothalamus controls the release of vasopressin from the posterior pituitary.

a. If ECF is too concentrated [i.e. too many solutes and not enough solvent (water)], vasopressin is released, and water diffuses out of distal and collecting tubules (and is picked up by the peritubular capillaries) which makes the urine less dilute and more concentrated.

b. If ECF is too dilute [i.e. not enough solutes and too much solvent (water)], vasopressin is not released, water is not reabsorbed in the distal and collecting tubules, and the urine is dilute

c. Range of urine concentration is 100 to 1400 mosm/liter

d. NOTE that urine production cannot be completely halted, even when dying of thirst. Your body will use any available water to produce a very concentrated urine to get rid of wastes. When you die of thirst, you literally piss your life away.

TOPIC 22

INPUT & OUTPUT of FLUIDS & IONS

Balance Concept

(Fig. 19.2)

1. If the amount of fluids and ions are to remain stable in body, input must equal output

2. Not all input and output pathways are regulated

a. Most input pathways are poorly regulated

- people will eat and drink what they want even if they don't need it

- H+ ions are uncontrollably produced internally

b. Some output poorly regulated

- salt, water and H+ are lost uncontrollably through vomiting and swearing

c. Humans regulate water, salt and H+ balances primarily through kidney function

TOPIC 22

INPUT & OUTPUT of FLUIDS & IONS

Types of Input and Output

(Fig. 19.1 & 19.3)

1. Input:

a. From Environment:

- Ingestion, inhalation, absorption

b. Metabolically Produced:

- products (e.g. amino acids) and by-products (e.g. H+ and water) of metabolic processes

2. Output:

a. Excretion to Environment:

- through kidneys, digestive tract, lungs, body surface (e.g. urine, feces, sweat, water vapor in breath, sloughed off skin)

b. Metabolically Consumed

TOPIC 22

FLUID & ION DISTRIBUTION in BODY

(Review from Topic 1)

Fluid Compartments Within Body

(Fig. 1.5)

1. Intracellular Fluid (ICF): within cells

2. Extracellular Fluid (ECF):

a. outside cells

b. further compartmentalized into

- plasma

- interstitial fluid

- boundary is capillary walls

3. Boundary between ECF and ICF are cell membranes

TOPIC 22

FLUID & ION DISTRIBUTION in BODY

(Review from Topic 1)

Ion Distribution Among Compartments

Table 4.1

Only know distribution... don't need to memorize the exact figures

TOPIC 22

FLUID & ION DISTRIBUTION in BODY

(Review from Topic 1)

Movement of Water and Ions Between ECF and ICF

1. Water moves freely between ECF and ICF

a. This movement is determined by osmotic effects alone

2. Ions do not move easily between ECF and ICF

a. Solute movement restricted across cellular membranes

b. Cellular proteins in the ICF usually can't leave cells and generally are not found in the ECF

c. Na+ and K+ and their associated anions are unequally distributed between the ECF and ICF; this is maintained in large part by the Na⁺- K⁺- ATPase pump

TOPIC 22

FLUID & ION DISTRIBUTION in BODY

(Review from Topic 1)

Regulation of Fluid and Ion Distribution:

the ECF is intermediate between the ICF and the external environment

1. The ECF is intermediate between the ICF and the external environment.

a. All exchanges of water and solutes between the ICF and the external environment must go through the ECF.

2. Plasma is the only fluid that has its volume and composition regulated. However, if plasma volume or composition changes...

a. The interstital fluid also changes

b. The ICF changes to the extent allowed by cell membrane permeability

3. Why you must regulate fluid and ion levels...

a. ECF Volume must be regulated to maintain blood pressure. Maintenance of salt balance is the primary way that ECF volume is regulated over the long term

b. ECF osmolarity (mg solutes/ml fluid) must be regulated to prevent shrinking or swelling of cells because ECF osmolarity affects ICF osmolarity. Maintenance of water balance is the primary way this is accomplished.

c. ECF volume and ECF osmolarity are intimately related to each other!

TOPIC 22

REGULATION of ECF VOLUME:

CONTROLLING the AMOUNT of Na+

Purpose...

*LONG TERM regulation of blood pressure by regulating plasma volume, which is accomplished by regulating the total quantity of Na+

1. Baroreceptor reflex and fluid shifts between the plasma and interstitial fluid are imprtant SHORT TERM mechanisms of regulating blood pressure.

2. If plasma volume is too far from normal, short term mechanisms are ineffective, so amont of Na+ must be regulated

3. Increases in Na+ lead to increases in ECF volume (because of osmotic forces: if you hold on to Na+, you automatically hold onto water too) and hence increase blood pressure; decreases in Na+ lead to decreases in ECF volume and hence decreases in blood pressure

TOPIC 22

REGULATION of ECF VOLUME:

CONTROLLING the AMOUNT of Na+

Na+ Balance...

1. INPUT: eating salt; not well controlled (most Americans eat way more salt than is needed)

2. OUTPUT: loss of salt in sweat, feces, and urine; only excretion in urine is regulated

TOPIC 22

REGULATION of ECF VOLUME:

CONTROLLING the AMOUNT of Na+

Mechanisms Regulating Na+ Excretion in Kidney...

1. Control of filtration rate in kidney:

a. Increasing filtration rate causes an increase in Na+ filtration and hence Na+ excretion; water is excreted along with the Na+, so ECF volume decreases (BP decreases)

b. decreases in filtration rate leads to decrease in Na+ filtration and excretion; Na+ and associated water conserved, which leads to an increase in ECF volume (BP increases)

2. Control of Na+ reabsorbed in kidneys (Fig. 18.3, 19.15, 19.16, 19.18)

a. In proximal tubule and loop of Henle, a constant percentage of filtered Na+ is reabsorbed, regardless of the absolute amount present

b. In the distal tubule, Na+ reabsorption is regulated

TOPIC 22

REGULATION of ECF VOLUME:

CONTROLLING the AMOUNT of Na+

Mechanisms Regulating Na+ Excretion in Kidney:

primary positive regulation system...

... is the renin-angiotensin-aldosterone system; you can upregulate or downregulate this system to alter Na+ and hence BP

1. If Na+ levels FALL (which causes a decline in ECF volume and blood pressure), the juxtaglomerular apparatus secretes the hormone renin into the blood.

2. Renin activates angiotensinogen by converting it to angiotensin I, which is then converted to...

3. angiotensin II by angiotensin converting enzyme produced by the lungs.

4. Angiotensin II then stimulates the adrenal cortex to secrete...

5. aldosterone, which increases Na+ reabsorption in the distal and collecting tubules by adding more Na⁺-K⁺-ATPase pumps to the basolateral membranes

6. This promotes Na+ retention, and so increases ECF volume and arterial blood pressure

7. Angiotensin II also is vasoconstrictor, stimulates thirst, and stimulates vasopressin (which induces water retention by the kidneys) all of which also result in an increase in ECF volume and arterial blood pressure

TOPIC 22

REGULATION of ECF VOLUME:

CONTROLLING the AMOUNT of Na+

Mechanisms Regulating Na+ Excretion in Kidney:

primary negative system is the atrial natriuretic peptide (ANP) system...

1. The heart produces ANP and stores it in the atria

2. When ECF volume increases too much, cardiac cells are stretched and ANP is released.

3. ANP inhibits Na+ retention in the distal parts of the nephron, inhibits renin and aldosterone secretion, and increases GFR by dilating the afferent arterioles in the nephrons.

4. These actions decrease Na+ retention, and hence lower ECF volume and arterial blood pressure

TOPIC 22

REGULATION of ECF OSMOLARITY:

CONTROLLING WATER BALANCE

PURPOSE: Regulation of ICF Osmolarity:

how ECF osmolarity (mg solutes/ml fluid) affects ICF osmolarity...

1. ECF hypertonicity (usually by dehydration) leads to ICF hypertonicity because water moves from ICF to ECF by osmosis. This causes cells to shrink which can lead to mental impairment and circulatory shock.

*The ECF has lower water and higher salt concentration so water in ICF moves to ECF to lower the salt concentration until it equals the salt concentration in ICF.

2. ECF hypotonicity (usually overhydration) leads to ICF hypotonicity because water moves by osmosis from ECF to ICF. This can lead to brain dysfunction and muscle weakness

3. Isotonic fluid loss (usually by hemorrhage) occurs when water and solutes lost together. This does not impact ICF volumes, but does lead to a decline in ECF volume (BP low).

TOPIC 22

REGULATION of ECF OSMOLARITY:

CONTROLLING WATER BALANCE

PURPOSE: Regulation of ICF Osmolarity:

mechanisms of water regulation...

1. Hypothalamic osmoreceptors monitor ECF osmolarity and initiate responses.

2. High osmolarity= hypertonic (too little water) Fig. 19.11

a. Vasopressin released and thirst stimulated; the vasopressin causes the kidneys to reabsorb more water so less is lost in the urine, and being thirsty causes you to drink more water. Urine still produced, but it has a very high concentration of solutes (max. of 1400 mosm/l).

3. Low osmolarity= hypotonic (too much water)

a. Vasopressin release inhibited; thirst inhibited, and reabsorption of water in the kidneys slowed or discontinued. Urine produced has a low concentration of solutes (minimum of 100 mosm/l).

REFER TO CHART!!!!!!!

HYPERTENSION:

1. Hypertention: BP > 140/90

2. Causes in only 10% of cases identified

3. 25% of Americans have it

HYPERTENSION:

Primary Causes

1. salt management problems by kidneys

2. plasma membrane abnormalities (Na-K-ATPase pump)

3. angiotensinogen gene variation

HYPERTENSION:

Secondary Causes

1. cardiovascular: atherosclerosis

2. renal: kidney diseases= increased salt load

3. endocrine:

a. excess epi and norepi from adrenal tumors

b. excess aldosterone because of adrenal problems

4. neurogenic:

a. baroreceptors or cardiovascular control center

b. brain tumors

HYPERTENSION:

Results of Hypertension

1. Baroreceptors reset to higher pressure

2. Increased heart workload

a. Heart attacks

3. Blood vessel damage

a. More atherosclerosis

b. mi's (heart attack) plus strokes

c. aneurisms (blood vessel breaks)

d. loss of vision (damage to blood vessels in eyes)

HYPERTENSION:

Interventions

1. reduce salt intake

2. increase urine output to lower salt and water in ECF

3. OVERALL: reduce plasma volume and/or peripheral

4. lose weight

TOPIC 23

ACID/BASE BALANCE

Background:

Why regulate acid-base balance?

1. only a narrow pH range is compatible with life

2. effects of pH fluctuations

a. changes in muscle and nerve excitability

- acidosis (too much H+) depresses CNS

- alkalosis (too little H+) causes overexcitability

b. change enzyme activities profoundly

3. influence K+ levels (see Topic 22)

TOPIC 23

ACID/BASE BALANCE

Background:

Acid Chemistry (review)

1. An acid is a hydrogen containing substance that dissociates in solution to produce

a. free H+

b. anions (negatively charged ions)

TOPIC 23

ACID/BASE BALANCE

Background:

Base Chemistry (review)

1. a base is a substance that binds with free H+ and removes it from solution

TOPIC 23

ACID/BASE BALANCE

Background:

pH (review)

1. pH= log 1/[H+]

2. low pH= high acid

3. every unit change in pH= tenfold change in [H+] because it is a log scale

TOPIC 23

ACID/BASE BALANCE

Background:

Buffers (review)

1. a mixture of several chemical compounds in solution that minimize pH changes when an acid or a base is added or removed from the solution

TOPIC 23

ACID/BASE BALANCE

Chemical buffer systems are first line of defense against pH fluctuations:

1. Buffers respond within fractions of a second to changes in [H+]. Although buffers pick up H+ very rapidly, they do not eliminate them from the body, so they are not a solution to long term imbalances.

TOPIC 23

ACID/BASE BALANCE

Chemical buffer systems are first line of defense against pH fluctuations:

HCO₃^- Buffer...

1. Very effective buffer and is most important in body for buffering pH changes caused by anything other than CO₂ generated acid (because HCO3- is produced from CO2 too)

2. H⁺ + HCO3^- <--> H₂CO₃ <--> CO₂ + H₂O

a. this is a very important buffering system. The above reations is almost alwyas catalyzed in the body by carbonic anhydrase

3. When H+ is added from any source other than CO2, drives above reaction to right; H+ ions are absorbed, and CO2 is produced.

4. When H+ falls, above reaction is driven to the left, and CO2 and water combine to produce H+ and HCO3-

TOPIC 23

ACID/BASE BALANCE

Chemical buffer systems are first line of defense against pH fluctuations:

Protein Buffers...

1. Proteins have both acidic and basic groups that can take up or give up H+

2. Most important in ICF, where most proteins exist

TOPIC 23

ACID/BASE BALANCE

Chemical buffer systems are first line of defense against pH fluctuations:

Hemoglobin acts as a buffer...

1. As CO₂ diffuses into the blood at the capillaries, if dissociates:

CO₂ + H₂O <--> H₂CO₃ <--> H⁺ + HCO₃^-

2. Deoxy-Hb has a great affinity for and binds the free H+ at the capillaries; in the lungs, the reaction is reversed and the Hb gives up the H+ to bind O₂ instead. The H+ then binds with HCO3- to reform CO2 and water

3. Hb very important in buffering the blood.

TOPIC 23

ACID/BASE BALANCE

Chemical buffer systems are first line of defense against pH fluctuations:

Phosphate Buffers...

1. Important buffer in the ICF (secondary to proteins)

2. Only buffer found in urine

a. Humans consume excess phosphate which is excreted in urine

b. The phosphates within the tubular system act as a buffer

TOPIC 23

ACID/BASE BALANCE

Pulmonary ventilation is the second line of defense against pH flucuations:

1. The respiratory system responds in increases in arterial [H+] within a few minutes.

2. When [H+] increases, ventilation rates increase

3. This leads to a decrease in plasma [H+] because when you eliminate CO2, you drive the following reaction to the left and get rid of H+:

CO₂ + H₂O <--> H₂CO₃ <--> H⁺ + HCO₃^-

4. Conversly, when [H+] falls, ventilation is reduced, which causes a build up of CO2, drives the reaction to the right, and causes an increase in [H+].

5. Lungs rid the body fluids of 100 times more H+ (derived from carbonic acid) than the kidneys remove from non-carbonic acid sources

6. Person can (unless they have a respiratory disease) always alter ventilation rates to change plasma acid-base balance.

7. Respiratory system usually only returns pH 50% to 75% of normal, because as pH gets closer to normal, the less the ventilation rates are influenced

TOPIC 23

ACID/BASE BALANCE

Kidneys are 3rd line of defense against pH flucuations

1. Slowest but most potent

2. Can Regulate:

a. Removal of H+ created by any source

- All non-carbonic acids must be removed by kidney (lungs can only eliminate carbonic acid)

- Carbonic acid also removed by kidneys; very important in cases of respiratory pathologies

b. Removal of HCO3-

c. pH almost exactly

3. Do all this by adjusting 3 substances

a. H+, HCO3-, NH₃ (ammonia)

TOPIC 23

ACID/BASE BALANCE

Kidneys are 3rd line of defense against pH flucuations:

Mechanism of regulation during acidosis...

1. High secretion of H+ into tubules

a. H+ in the tubular system is buffered before it is excreted. First it combines with the filtered HCO3- in the tubular system to produce water until all HCO3- is used up. Next the H+ combines with filtered phosphate in the tubules and the H₂PO₄^- produced is excreted in the urine. Once all phosphate buffer in urine is used up, NH3 produced from amino acid glutamine combines with H+ and NH₄⁺ is excreted in urine.

2. HCO3- is reabsorbed into the plasma from the tubules.

TOPIC 23

ACID/BASE BALANCE

Kidneys are 3rd line of defense against pH flucuations:

Mechanism of regulation during Alkalosis...

1. Rate of H+ (via (CO2) secretion reduced (note: H+ cannot be reabsorbed)

2. Rate of HCO3- filtration increased

a. Plasma levels of HCO3- higher than normal under alkalosis because not as much H+ for HCO3- to bind

3. RESULT: less H+ in urine, more HCO3- in urine, urine becomes alkaline. Continues til acid/base balance restored.

TOPIC 23

ACID/BASE BALANCE

Acid-Base Imbalances:

Overview

1. Changes in pH are reflected by changes in the ratio of [HCO3-] to [CO2]

a. When the ratio of [HCO3-]/[CO2] is less than 20/1, acidosis exists

b. When ratio of [HCO3-]/[CO2] is greater than 20/1, alkalosis exists

2. The concentration of HCO3- in the ECF is 600,000 times the concentration of H+; hence when CO2 produces one H+ and one HCO3-, this affects the concentration of H+ much more than the concentration of HCO3-.

TOPIC 23

ACID/BASE BALANCE

Acid-Base Imbalances:

Respiratory Acidosis: Hypoventilation

1. Causes:

a. Lung disease

b. Depression of respiratory center by drugs or disease, nerve or muscle disorders that reduce respiratory capability, or holding your breath (only a short term event)

2. Results:

a. CO2 elevated, HCO3- unchanged

- Each CO2 produces one H+ and one HCO3-, which affects [H+] much more than the [HCO3-]

b. [HCO3-]/[CO2] drops below 20/1

3. Compensation:

a. Chemical buffers take up extra H+

b. Lungs can NOT get rid of extra H+ since lungs are problem

c. Kidneys compensate in the long term

TOPIC 23

ACID/BASE BALANCE

Acid-Base Imbalances:

Respiratory Alkalosis: Hyperventilation

1. Causes:

a. Fever, anxiety, aspirin poisoning, exposure to high altitude

2. Results:

a. Excessive loss of CO2, so too little H+ in ECF

b. HCO3- stays the same

c. [HCO3-]/[CO2] increases above 20/1

3. Compensation:

a. Chemical buffers release H+

- this tends to reduce the hyperventilation quickly

b. If alkalosis persists for hours/days, kidneys respond.

TOPIC 23

ACID/BASE BALANCE

Acid-Base Imbalances:

Metabolic Acidosis

1. Causes:

a. sever diarrhea

- HCO3- lost from GI tract

b. diabetes mellitus

- abnormal fat metabolism (in place of glucose) results in production of keto acids

c. strenuous exercise

- anaerobic metabolism leads to H+ production

d. severe renal failure

2. Results:

a. CO2 (and hence [H+] remain normal)

b. HCO3- reduced (either through loss or through buffering non-CO2 produced acids)

c. [HCO3-]/[CO2] drops below 20/1

3. Compensation:

a. buffers take up extra H+

b. lungs blow off additional CO2

c. kidneys excrete more H+ and conserve more HCO3-

- NOTE: if renal failure is the cause, this can not occur, and complete restoration of acid base balance is NOT possible

TOPIC 23

ACID/BASE BALANCE

Acid-Base Imbalances:

Metabolic Alkalosis

1. Causes:

a. Vomiting: causes loss of non-carbonic acid H+ from GI tract

b. ingestion of alkaline drugs (e.g. baking soda for upset stomach)

2. Results:

a. increase in HCO3-

b. no change in CO2

c. [HCO3-]/[CO2] increases above 20/1

3. Compensation:

a. chemical buffers liberate H+

b. ventilation reduced

c. after several days, kidneys conserve H+ (by secreting less H+) and excrete more HCO3-