Physiology Credit Test 2Nd Semester

Front 1

3 system of defense againts AB disturbance:

Back 1

1. Buffersystems of blood:
a) Phosphate buffers
b) Proteins
c) Bicarbonate

2. Respiratory system:
Controlling extrcellular consentration of CO2

3. Kidneys:
Secretion/ resorbtion of H+

Front 2

Respiratory regulation of ABB:

Back 2

Regulation CO2 by ventilation:
a) Hyperventilation--> hypokapnia
b) Hypoventilation--> hyperkapnia

Front 3

How does regulation of CO2 by ventilation regulate pH:

Back 3

H2O + CO2<--> H2CO3 <--> HCO3- + H+

If you eliminate CO2 the reaction will be shift to the right to make more CO2 which will need H+ as a substrate

Is dependent on buffer capacity from bicarbonate which is dependent on the carbonic acid concentration

Front 4

How do kidneys regulate ABB:
(Slow reaction, takes a couple of days)

Back 4

1. Secretion of H+
2. Secretion or resorption of bicarbonate
3. Secretion of ammonia

Front 5

Where is H+ secreted and HCO3- resorbed?

Back 5

Proximal tubule

Front 6

Mechanism of H+ secretion and bicarbonate resorption in proximal tubule:

Back 6

In cell:
1. H2O + CO2 (from metabolism, blood & tubular lumen) ---> H2CO3 catalyzed by carbonic anhydrase
2. H2CO3 dissociates
3. Bicarbonate is resorbed to blood and H+ is secreted by Na+ antiport

In tubular lumen:
4. Secreted H+ reacts with filtrated bicarbonate----> H2CO3
5. H2CO3 dissociates---> H2O + CO2
6. H+ is lost in urine as water and CO2 diffuses into cell where it reacts with water all over again

Can also react with H3PO4

Front 7

How is bicarbonate resorbed from cell to blood in kidneys:

Back 7

1. By symport with Na+

2. By antiport with Cl-

Front 8

Where is H+ secreted:

Back 8

1. Proximal tubule
2. Distal tubule
3. Collecting duct

Front 9

Blood volumes of the lungs
a) Total
b) In the cappilaries

Back 9

a) 450 ml (9% of total body volume)

b) 70 ml are in the capillaries, the rest in aa. and vv.

Front 10

Pressure in lungs varies due to hydrostatic pressure. Whats the pressure in:
a) Apical part of lungs in upright position
b) The level of the heart
c) Basal part of lungs in upright position
d) Mean pressure in systole and diastole

Back 10

a) 10 mmHg

b) 25 mmHg

c) 33 mmHg

d) Systole: 15 mmHg, Diastole: 8 mmHg

Front 11

Blod flow distribution zones:

Back 11

Zone 1: No blood flow during the entire cardiac cycle because alveolar air pressure is higher then alveolar capillary BP

Zone 2: Intermittent blood flow only in systole because systolic BP is higher then alveolar air pressure. But alveolar air pressure is higher then diastolic BP

Zone 3: Continuos blood flow because capillary BP remains higher then alveolar air pressure during entire cardiac cycle.

Front 12

Effect of exercise on pulmonary hemodynamics:

Back 12

Blood flow can increase 7 times in apical area and 4 times in basal area as a result of increased cardiac output ==> Zone 3 ill parts of the lung

Front 13

Effect of suspine position on pulmonary hemodynamics:

Back 13

When lying down ventral part of lung only gets 5 cm over heart resulting in zone 3 in all levels of the lung

Front 14

During what kind of abnormal condition do zone 1 of the lungs predominate?

Back 14

Hypovolemic shock or when breathing against a 10 mmHg positive airway pressure (CPAP valve 10 cm H20)

Front 15

Cardiac output can increase 4-7 times during exercise and the lungs respond to this in 3 ways:

Back 15

1. Increasing number of open capillaries

2. Distending of capillaries to increase blood flow

3. Increasing pulmonary arterial pressure

The two first increase blood flow without increasing pulmonary pressure which conserves energy of right side of heart and prevents pulmonary edema

Front 16

Local effect of low PO2 on alveolar capillaries:

Back 16

Vasoconstriction to redirect blood flow to better ventilated alveoli

Front 17

Characteristics of diffusion gases:

Back 17

Lipid soluble

Front 18

How many alveoli are there in lungs and what is the total surface area for diffusion?

Back 18

300 million alveoli makes up 140 square meters are for gas exchange

Front 19

Blood air barrier is formed by: (6)

Back 19

1. Thin layer of surfactant
2. Cellmembrane of type 1 pneumocytes
3. Basement membrane (collagen type IV)
4. Interstitial space
5. Basement membrane of capillary
6. Cellmembrane of endothelial cell of capillaries

Front 20

Factors influencing diffusion: (4)

Back 20

1. Thickness of membrane (edema)
2. Surface area (Emphysema)
3. Diffusion coefficient of the gas substance (CO2 23 times higher then O2)
4. Diffusion gradient made up by partial pressures of gases on both sides of the membrane

Front 21

Respiratory defense reflexes:

Back 21

1. Cough reflex
2. Sneeze reflex

Front 22

Initiation of the cough reflex:

Back 22

1. Bronchi and trachea are sensitive to foreign matters causing irritation
2. Larynx, carnia, terminal bronchioles and alveoli are sensitive to chemical stimuli (sulfur dioxide or chlorine gas)

Front 23

Neural control of cough reflex:

Back 23

Stimuli--> Afferent nerve impuls by Vagus n. to medulla ---> automatic sequence of events triggered by neuronal circuits of the medulla

Front 24

Mechanism of coughing after nerve stimuli: (5)

Back 24

1. Rapid inspiration of 2,5 L
2. Epiglottis and vocal cords shut tightly
3. Expiratory muscles contract while epiglottis and vocal cords still being shut---> pulmonary pressure rise above 100 mmHg
4. Vocal cords and epiglottis open widely---> explosive expiration (75- 100 miles/h)
5. Expulsion of foreign substance

Front 25

Differences between cough and sneeze reflex:

Back 25

1. Initiation from irritation in nasal passageways
2. Afferent impulse by V. cranial nerve
3. Uvula is depressed
4. Expulsion through nose not mount

Front 26

Effectiveness of respiratory defense reflexes:

Back 26

Particles larger then 6 micrometers is not allowed to enter the lungs. Particles 1-5 micrometers in size can settle in bronchioles. Smaller then 1 micometer adhere to alveolar fluid

Front 27

Cheyne- Stokes respiration
a) Characteristics
b) Mechanism

Back 27

a) Periodic breathing characterizes by respiration increasing in depth and frequency followed by a decrease in frequency and depth and then a period of apnea before the cycle repeats itself

b) Hyperventilation decreases CO2 and increases O2 in alveolar blood. It takes a couple of seconds before the blood reaches resp. center in medulla, and then the low CO2 depresses breathing. This leads to increase in CO2 in alveolar blood, which again needs a couple of seconds to reach medulla. When it does it is very acidic and stimulates heavy breathing. This happens in everyone, but is normally damped by dissolved CO2 and O2 in the tissues around resp. center inhibiting excess buildup of CO2.

Front 28

Two separate conditions where damping factors of CO2 can be overridden leading to Cheyne- Stokes respiration:

Back 28

1. Long delay in transport of blood from alveolar capillaries to medulla allowing changes in CO2 occurring much longer then normal. (Severe heart failure)

2. Increased negative feedback gain in respiratory center leading to a much greater ventilatory response to small changes in CO2 then needed. Normally increase of CO2 by 3 mmHg would increase respiration b 2-3 fold. In this condition the increase could be up to 20 folds. (Stroke, head trauma)

Front 29

Biot respirations
a) Characteristic
b) Mechanism

Back 29

a) Rapid shallow breath followed by periods of apnea

b) Severe trauma to medulla oblongata or severe stroke to the same region

Front 30

Kussmaul respirations:
a) Characteristics
b) Cause

Back 30

a) Deep rapid breathing

b) A compensation mechanism to eliminate CO2 in severe acidosis, typically in ketoacidosis.

Front 31

Lung elasticity (retractive power) causing passive recoil of lungs during passive expiration is due to:

Back 31

1. Elastic resistance due to elastic fibers (elastin in lung parenchyma). Elastic fibers decreases with age ---> increased residual volume

2. Alveolar surface tension by liquid molecules that has a tendency to adhere to each other trying to decrease the surface of the liquid of the alveoli and making expansion difficult. Inhibited by surfactant

3. Configuration of bones, mm. and connective tissue of chest wall also affects chest walls elasticity

Front 32

Surfactant
a) Composition
b) Production
c) Function

Back 32

a) Phospholipid+ cholesterol and protein

b) Produced from week 20 of gestation and are fully functional from week 36. High risk under 29 weeks. Produced by type II pneumocytes

c) Maintaining alveolar stability by decreasing surface tension between the air/ alveoli interface.

Front 33

Airway resistance:

Back 33

Describes the mechanical factors that limit the access of inspired air to the pulmonary alveoli and thus determine airflow. Greatest in the bronchi of intermediate size, between fourth and eight bifurcation.

Resistance is calculated by Poiseuille`s law and is directly proportional to the length of the vessel and the viscosity of blood, and inversely proportional to the radius to the fourth power

Front 34

Halving the radius of the airways will increase the resistance:

Back 34

16 times due to radius to the fourth power

Front 35

Pleural pressure:

Back 35

- 5 cm of H2O which is the amount of suction needed to keep the lungs open in resting level. - 7,5 during inspiration due to expansion of chest wall ---> suction that inflates the lungs

Front 36

Alveolar pressure:

Back 36

Equal to the atmosphere when the airways are open in the end of inspiration and the end of expiration, is set to zero as reference pressure.
Inspiration: Alveolar pressure is lower then atmospheric--> inflow of air (-1)
Expiration: Alveolar pressure is greater --> expulsion of air (+)

Front 37

Transpulmonary pressure:

Back 37

Recoil pressure, the difference between alveolar pressure an pleural pressure which is a measure of the lungs compliance

Front 38

Compliance:

Back 38

A measure on the lung and chest walls distensibility. Represents the ability to resist recoil, is therefore reciprocal (opposite) to elasticity. Is indicated by how much the lung will expand in volume for each unit change in transpulmonary pressure. Is determined by alveolar surface tension and the elastic recoil of lungs and chest wall. (200 ml of air per 1 cm water change in transpulmonary pressure

Front 39

Causes of increased and decreased compliance:

Back 39

1. Increased: Loss of elastic recoil making lungs easy to inflate (emphysema)

2. Decreased: Lungs and chest wall are abnormally stiff or difficult to inflate due to fibrosis, pneumonia, RDS

Front 40

Work of breathing:

Back 40

The muscular effort (oxygen and energy) needed for ventilation. Can be divided into 3 fractions:
1) Work required to expand the lung and chest elastic forces, called compliance work or elastic work

2) Work required to overcome the viscosity of the lungs and chest wall called resistance work

3) Work required to overcome airway resistance to movement of air unto the lungs called airway resistance work

Front 41

Energy required for respiration:

Back 41

Normal breathing: Only 3-5 % of total energy is needed for pulmonary ventilation

Heavy exercise: If the patient also has increased airway resistance or decreased compliance the energy requirements can increase 50- fold.

Front 42

Pneumothorax
a) What?
b) 3 types:

Back 42

a) Air in the pleural space caused by rupture of visceral pleura or parietal pleura and chest wall. Destroys negative pressure--> lungs elastic forces are no longer held in check---> collapsing of lung towards hilus

b) 1. Open pneumothorax
2. Closed pneumothorax
3. Spontaneous pneumothorax

Front 43

Open pneumothorax:

Back 43

Air flow in and out of a hole in the visceral or parietal pleura. Pleural pressure = atmospheric pressure

Front 44

Closed pneumothorax (valve pneumothorax):

Back 44

The site of puncture of the chest wall acts as a one way valve allowing air to be sucked in during inspiration, but the tissue flap (valve) closes during expiration, trapping air inside pleural cavity ===> tension pneumothorax

Front 45

Tension pneumothorax:

Back 45

A result from closed one- way valve pneumothorax. The more air is trapped in the pleural cavity the more the pressure rices. This eventually compresses the heart leading to obstructive shock. The heart then compresses the healthy lung impairing ventilation of this one.

Front 46

Spontaneous pneumothorax:

Back 46

1. Primary spontaneous pnuemothorax: Rupture of a bleb in the lung (dark, tall men)

2. Secondary pneumothorax:
Pneumothorax secondary due to COPD or tuberculosis

Front 47

Hyperbarism:

Back 47

Lungs exposed to extremely high alveolar pressure in order to keep lungs from collapsing beneath the sea where the pressure is tremendously increased

Front 48

A person 10 meters beneath the sea is exposed to:

Back 48

2 atmospheres pressure. 1 Atm from the weight of air above the water and 1 Atm from the weight of water itself

Front 49

Effect of sea depth on the volume of gases (Boyle`s Law):

Back 49

Increasing sea depth depresses gases to smaller volumes. The volume to which a quantity of gas is compressed is inversely proportional to the pressure (Boyle`s Law). 1 L gas is compressed to 0,5 L 10 meters beneath the sea

The physiological relevance of this is that increasing pressure can collapse the airways.

Front 50

Effects of breathing gases with high partial pressures on the body:

Back 50

1. Nitrogen narcosis

2. Oxygen toxicity

3. Carbon dioxide toxicity (only in nonfunctional diving gear)

4. Decompression sickness when ascending

Front 51

Nitrogen narcosis (raptures of depths):

Back 51

Breathing compressed nitrogen will give signs of narcosis in divers in about 36 meters for 1 hour. At 60 meters the diver becomes drowsy and beneath 75 meters the divers becomes completely useless and goes in full narcosis

Front 52

Mechanism of nitrogen toxicity:

Back 52

The same as for gas anesthetics. Nitrogen under high pressure will dissolve in fatty substances in neuronal membranes and altering the ionic conduction through the membranes which reduces neuronal excitability.

Front 53

Oxygen toxicity at high pressures:

Back 53

When PO2 in the blood rises above 100 mmHg the amount dissolved in plasma increases markedly----> increased O2 delivery to tissues---> Hb- Oxygen buffer mechanism is not able to maintain tissue PO2 within the safe range of 20- 60 mmHg

Front 54

Acute oxygen poisoning:

Back 54

Breathing oxygen at 4 atmosphere pressure of oxygen (PO2 3040 mmHg) will cause seizures followed by coma within 30- 60 min.

Front 55

Acute oxygen poisoning symptoms:

Back 55

1. Seizures
2. Nausea
3. Dizziness
4. Vision disturbances
5. Disorientation

Front 56

Excessive intracellular oxidation as a result of oxygen toxicity:

Back 56

Leads to formation of free radicals (superoxide and hydrogen peroxide) which has a free valence electron which is very reactive.
At normal partial pressure of O2 peroxidases, catalases and superoxide dismutases remove free radicals. But with alveolar PO2 above 2 atmospheres PO2 the Hb- oxygen buffering system fails to maintain oxygen level between 20- 60 mmHg---> tissue PO2 can rise hundreds of thousands mmHg---> free radical formation exceeds removal.

Front 57

Decompression sickness (The bends, Caissons disease):

Back 57

According to Henry`s law when the pressure of a gas over a liquid decrease the amount of gas dissolved in the liquid will decrease.

When a divers tissues have been equilibrated by a high nitrogen pressure, as long as the diver remains deep beneath the sea the pressure compresses all body tissues keeping N2 dissolved. But if the diver ascend the pressure of dissolved N2 in the body will be much higher then the total pressure exerted on the body, therefore the gas escapes the liquid form and and form bubbles of nitrogen in blood which blocks vessels.

Can have joint pain, neurological symptoms, infarction and "The Chokes" (a lot of microinfarctions in the lung capillaries)

Front 58

Treatment of decompression sickness:

Back 58

Recompression in pressure tank to the pressure and depth of the dive and then gradual decompression following current procedures. Then nitrogen will be eliminated normally by lungs.

Front 59

Renal clearance:

Back 59

Is the volume of plasma that is completely cleared of a substance by the kidneys per unit of time.

Front 60

Clinical relevance of measuring renal clearance:

Back 60

It provides a useful way of quantifying the excretory function of the kidneys, and can be used to quantify the rate at which blood flows through the kidneys as well as the basic functions of the kidneys:
- Glomerular filtration
- Tubular reabsorption
- Tubular secretion

Front 61

Clearance is equal to GFR if certain conditions of the filtrated substance are met:

Back 61

GFR is the rate at which fluid are filtered into Bowmans capsule.
Can be measured by measuring the excretion and plasma level of a substance (stable plasma level) that can be freely filtered through the glomeruli and is neither secreted nor reabsorbed by the tubules. E.g. inulin (fructose polymer)

Front 62

GFR formula:

Back 62

Clearance: Excretion rate of x / Plasna concentration of x=
GFR= U x V/P
Ux= Concentration of inulin in the urine
V= Urine flow rate
Px= Concentration of substance in plasma (inulin)

Normal value: 125ml/ min (7,5 l/h)

Front 63

Creatine clearance as a way of measuring GFR:

Back 63

Used clinically because inulin is to expensive. Creatinine is a byproduct of muscle metabolism and is released at a constant rate into plasma. It is relative to muscle mass. Increase of muscle mass or skeletal muscle injury releases more creatinine.
You need a blood sample and 24h diuresis. Normal plasma creatinine levels are: 0,7-1mg/dl.
Calculated from Urine concentration of PAH x 24h urine volume/ Plasma concentration of PAH= Clearance of creatinine

Front 64

Glomerular filtration, principles:

Back 64

Ultrafiltration of plasma through glomerular filter---> primary urine (ultrafiltrate)

Forces responsible for filtration: Frank Starling forces.
Filtration pressure= Hydrostatic pressure of glomerular capillary (45mmHg) - Oncotic pressure of glomerular capillary (24mmHg) - Hydrostatic pressure of Bowmans capsule opposing filtration pressure (8mmHg) = Net filtration pressure of about 13mmHg (normal value)

Front 65

Ultrafiltrate:

Back 65

Plasma without proteins of significant size. Small proteins like insulin be filtered.

Front 66

Glomerular filtration depends on:

Back 66

Pressure gradient across the filtration barrier

Blood circulation through the kidneys

Permeability of the filtration barries

Filtration surface

Front 67

Glomerular filter:

Back 67

1, 5 square meter surface, 180- 200 l are filtrated in the glomerular apparatus in which 97 % is resorbed back in the tubules (urine: 1,5- 2l)

Consist of:
Capillary epithelium (50- 100 nm pore size)
Basal membrane (250- 300 nm thick) with neg. charged heparan sulphate
Podocytes (epithelium of Bowmans capsule)

Front 68

Podocytes:

Back 68

Special epithelial cells which have numerous of pseudopia (pedicles) that form filtration slits (5 nm pores) along the capillary wall. Function to repel small proteins because due to a negatively charged glycocalyx coat.

Front 69

Filtration fraction:

Back 69

GFR/ RPF (renal plasma flow)

125ml/600ml= 0,20--> 20%
20% of the fluid that enters the kidneys are filtered (20% of the substances in plasma are filtrated, 80% are not filtrated and proceeds to the systemic circulation) If you increase the plasma concentration of feks Na+ more is filtrated, but the filtration fraction in % is still the same

Front 70

Regulation of glomerular filtration:

Back 70

Glomerular hydrostatic pressure and glomerular oncotic pressure determine GFR, so by regulating those two variables we regulate GFR. Hydrostatic pressure can be regulated by diameter of afferent!!! and efferent arterioles and by plasma protein level.

Ways to regulate those two variables are:
- Sympathetic stimulation
- Hormonal control
- Autoregulation by intrinsic feedback mechanisms
- Plasma protein level

Front 71

Sympathetic regulation of GFR:

Back 71

Sympathetic stimulation will vasoconstrict afferent and efferent arteriole which will decrease glomerular blood flow---> decrease in GFR.
(Kidneys have no parasympathetic innervation)

Front 72

Hormonal control of renal circulation and thus GFR:

Back 72

Adrenaline, nor- adrenaline and endothelin constrict afferent arteriole (or both) reducing GFR

Low BP----> Angiotensin II----> (raise renal resistance without a major change in GFR) constricts efferent arterioles ==> increasing glomerular hydrostatic pressure and increasing GFR. This also reduces blood flow in the peritubular capillaries which changes osmolarity to increase Na+ and H2O resorption in proximal tubule.

Endothelial derived nitric oxide causes vasodilatation and subsequent increase in GFR, the same does local mediators such as prostaglandins and bradykinin.

Front 73

Autoregulation of GFR:

Back 73

Myogenic autoregulation: mechanoreceptors in afferent arteriole release Ca2+ into smooth muscle cells in response to stretch from high BP---> vasoconstriction.
Na+ receptors in macula densa cells in distal tubule next to the juxtaglomerular apparatus reacts to an increase Na+ concentration causing vasoconstriction of afferent arteriole.

Renin (enzyme) released from juxtaglomerular cells in response to low renal blood flow constricts efferent arterioles (increasing GFR) and activates angiotensin I(I) which has a more potent vasoconstriction effect on efferent arterioles then renin.

Front 74

Protein diet influence of GFR:

Back 74

Plasma protein level will influence glomerular oncotic pressure which will influence GFR. High plasma protein level will give a high oncotic pressure which will oppose filtration, reducing GFR. But low plasma protein level will decrease oncotic pressure and thus increasing filtration pressure and GFR.

Front 75

Renin- angiotensin system:

Back 75

1. Decreased perfusion in mechanoreceptor cells in macula densa will release enzyme renin from juxtraglomerular cells
2. Renin cleaves the liver zymogen angiotensinogen to angiotensin I.
3. Angiotensin I is cleaved by ACE in the lung capillaries to angiotensin II.
4. Angiotensin II increase tubular resorption of Na+ and Cl- and retains H2O by it self and by releasing Aldosterone from Adrenal cortex. Constricts arterioles. Stimulates pituitary gland to release ADH which increases permeability of water in the collecting ducts--> resorption water.

Increased renal perfusion---> negative feedback to renin.

Front 76

Proximal tubule, morphology and main function:

Back 76

Morphology:
15 mm long and 55 micrometers in diameter, striated brush border epithelium for large surface area for resorption.
Function:
Reabsorption of the largest volume of solution filtered in the glomerular apparatus.
75- 80% of water is reabsorbed here.
Na+, Cl-, bicarbonate, K+, Ca2+, Mg2+ HPO4-2 and glucose is also reabsorbed here. (into vasa recta)
Result in isoosmotic solution.

Front 77

Proximal tubule reabsorption (Na+, glucose and AAs):

Back 77

1. Na+ is transported by primary active transport by Na+- K+ATPase from the interior of the epithelial cell to the blood--> low Na+ concentration inside the cell==> Na+ is transported down its conc. gradient across the luminal membrane
2. Glucose is reabsorbed by secondary active transport. Na+/K+ ATPase makes a con. gradient allowing facilitated diffusion of Na+ across the luminal membrane down its concentration gradient, which facilitates transport of glucose and AAs up its conc. gradient. Glucose and AAs are transported by Co-transport with Na+ at the apical membrane

Front 78

Proximal tubule reabsorption (Cl- and bicarbonate):

Back 78

In the first part of the tubule Na+ is reabsorbed by co-transport by glucose and AAs. But in the last part all glucose is reabsorbed and Na+ is reabsorbed in co transport with Cl-. Bicarbonate is also reabsorbed in the first part.

Front 79

Tubular reabsorption:

Back 79

Proximal tubule:
H2O, NaCl (65%), K+ (65%), bicarbonate (80- 90%), urea 50 %, AA, oligopeptides and proteins (100%), glucose (100%), Phosphates via sodium/phosphate cotransporter (Inh. by PTH) (85%), Ca2+ and Mg2+, lactate (100%)

Loop of Henle, thin descending limb:
NaCl (15%), H20

Loop of Henle, ascending limb:
NaCl (25 %), K+ (20 %), Ca2+, Mg2+

Distal tubule:
NaCl (5 %), Ca2+ and H2O

Collecting duct:
Na+, H2O, Urea and bicorbonate

Front 80

Transport mechanisms in tubular reabsorption:

Back 80

1. Primary active transport: Transport up a electricochemical gradient by consumption of ATP. (Na+, K+, H+, Ca2+)
2. Secondary active transport: One substance is transported down its concentration gradient, driving transport of the other substance up its cons. gradient. Co- (symport), or counter- (antiport) transport (Glucose, AAs, proteins, phosphates)
3. Pinocytosis (AAs, polypep., proteins)
4. Passive transport: Facilitated diffusion (Na+, Cl-, urea), filtration/ osmosis (H2O, CO2)
5. Ultrafiltration: Oncotc/ hydrostatic pressures.

Front 81

Tubular secretion:

Back 81

Transport of materials from peritubular capillaries to renal tubular lumen, mainly by active transport.
# Proximal tubule:
Uric acid, OXA, choline, histamine, steroids (countertransport with H+ from the lumen. H+ is secreted with countertransport with Na+)
2. Bile salts (ABC- transporter)
3. Penicillin (ABC- transporter
4. Steroid glucoronides (ABC- transporter)

# Distal tubule:
1. H+ is secreted into tubular lumen by countertransport with Na+. In the lumen it either combines with bicarb to reabsorb it or combine with ammonia or phosphates to be excreted
2. K+ is secreted by Na+/ K+ ATPase (2K+/ 1Na+)
3. Urea is secreted by countertransport with Na+

Front 82

Countercurrent systems:

Back 82

Is a system in the renal medulla that facilitates concentration of the urine as it passes through the renal tubules. It is done by active transport of Na+ to maintain medullary hyperosmolarity

Front 83

Factors contributing to hyperosmolarity in renal medulla (countercurrent systems):

Back 83

1. Active transport of Na+ and co- transport of K+ and Cl-. Ascending limb is not permeabel to water--> hypotonic solution
2. Active transport of ions from the collecting duct into the medullary interstitium
3. Facilitated diffusion of large amounts of urea from the inner medullary collecting ducts into medullary interstitium
3. Diffusion of only small amounts of water from medullary tubules into medullary intestitium, far less than the reabsorption of solutes into the medullary interstitium

Front 84

Countercurrent multiplier:

Back 84

Repetitive reabsorption of NaCl by thick ascending limb and continued inflow of NaCl from proximal tubule is called countercurrenet multiplier. This process gradually traps solutes in the medulla and multiplies the concentration gradient established by the active pumping of ions out of the thick ascending limb---> raising of interstitial fluid osmolarity to 1400mOsm/L

Front 85

Urea contributes to about 50 % of the osmolality made by the countercurrent system:

Back 85

1. No urea is reabsorbed in ascending loop of Henle. Na+ and H2O is reabsorbed in distal tubule, leading to high urea concentration in the collecting duct
2. Urea is passively absorbed in collecting duct down its cons. gradient. ADH increase reabsorption.
3. Water follow urea by osmosis
4. Urea enters the thin descending limb of loop of Henle providing an additional mechanism for forming hyperosomotic medullary interstitium.

Front 86

Countercurrent system of vasa recta:

Back 86

As blood descends into the medulla towards the papillae it becomes progressively more concentrated, partly by solute entry from interstitium and by loss of water to interstitium. At the bottom it has 1200mOsm/L in cons. As blood ascends it becomes less concentrated as solutes diffuse out to the interstitium. Very little net dilution of blood.

Front 87

Reabsorption of glucose:

Back 87

Normally 100 % of glucose is reabsorbed in the proximal tubule. It is transported from the tubular lumen into epithelial cell by secondary active transport with Na+ (does not require energy because Na+ moves down its concentration gradient which can be used to drive transport of glucose up its cons. gradient). Exits epithelial cell and enters capillary membrane by facilitated diffusion driven by its concentration gradient.

Front 88

Transport maximum of glucose:

Back 88

375mg/min. At this point, glucose concentration exceeds transport systems capability to transport glucose in the proximal part of the tubular cells---> glucosuria. This happens at plasma glucose consentration over 11 mmol/L

Front 89

Water reabsorption, concentration and dilution in the kidney:

Back 89

180 L of plasma are filtrated in glomerulus each day, leading to 0,5- 2L urine output. Water intake each day: 2,5L (drinks, food, metabolism), output: 2,5 L (urine, feces, respiration, sweat)

Reabsorption of water:
1. Proximal tubule: High water permeability (65%). Reabsorption of water is osmotically with ions by transcellular and paracellular diffusion.
2. Descending loop of Henle: (25%) Diffusion by osmosis to medulla and to vasa recta. Concentrates urine.
3. Ascending loop of Henle: Reabsorption of ions with out loss of water. Dilutes urine.
4. Distal tubule and collecting duct: H2O reabsorption through aquaproins.

Front 90

Reabsorption of water balance:

Back 90

1. ADH (antidiuretic hormone/ vasopressin) secreted from pituitary gland stimulate aquaporin synthesis and thus water reabsorption.

2. ANP (atrial natriuretic hormone) increase GFR and decrease Na+ reabsorption and thus decrease H2O reabsorption---> promoting diuresis.

Front 91

Urine concentration in the kidneys:

Back 91

In general the kidneys excrete excess water by forming dilute urine, and conserves water by concentrating urine. Urine osmolality may range from 50 mOsm/L to 1400 mOsm/L:
1. Primary urine: 300 mOsm/L
2. Proximal tubule: Isotonic with plasma; 300 mOsm/L
3. Descending loop of Henle: Hypertonic: up to 14 00 mOsm/L due to equilibration with the hypertonic medulla by water and Na+ reabsorption
4. Ascending loop of Henle: Hypotonic: down to 100 mOsm/L due to reabsorption of solutes but not water.
5. Distal tubule: Isoosmotic urine dure to resorption of both Na+ and water
6. Collecting duct: Hyperosmotic solution when ADH stimulates resorption of water (up to 14000 mOsm/L)

Front 92

ADH:

Back 92

Also known as arginine vasopressin is a peptide hormone produced by hypothalamus and released by posterior pituitary gland when the body is low on water causing water retention in collecting ducts.

Front 93

Control and release of ADH:

Back 93

1. Baroreceptors in aortic arch and carotid bodies register change in blood volume--> stimulates release
2. Osmoreceptors in hypothalamus register change in plasma osmolality (high osmolality stimulates release)
3. Angiotensin II stimulates ADH secretion
4. Ethanol and caffeine inhibits ADH secretion ---> no reabsorption of water in collecting ducts and increased diuresis

Front 94

Sodium concentration and reabsorption:

Back 94

ECF: 140 mmol/L, ICF: 10mmol/L. 99,6 % is reabsorbed. 65% in prox. tubule, 25 % in loop of henles and 9% in collecting duct.

Mechanism:
1. Apical/luminal surface: Passive diffusion down concentration gradient (cotransport with glucose and AAs)
2. Basolateral surface: Na+/K+ ATPase

Front 95

Regulation of Na+ concentration in ECF:

Back 95

1. Angiotensin: Stimulates Na+ transport in the basolateral membrane of tubular cells: resorption of Na+ and water.
2. Aldosterone: Stimulates synthesis of Na+/K+ ATPase in distal tubule--> increase Na+ reabsorption and therefore retains water. Increases K+ excretion.
3. ANP: Decrease Na+ reabsorption (decreasing ECF Na+ cons.) and increases GFR
4. Sympathetic stimulus: Decr. GFR--> less filtered Na+--> decr. Na+ excretion. Stim Na+ reabsorption and renin release.
5. Estrogen: Decrease Na+ excretion.
6. Glucocorticoids: Increases Na+ reabsorption, but also decrease GFR and therefore only slightly decreasing Na+ excretion.
7. Prostaglandin E2: Increase Na+ excretion

Front 96

Potassium concentration and reabsorption:

Back 96

90 % of ingested K+ are reabsorbed by kidneys. ECF cons: 4,2 mmol/L. ICF cons: 140 mmol/L.
65 % reabsorbed in prox. tubule, 27 % reabsorbed in asc. loop of Henle, 4 % secreted into collecting duct= 12 % are excreted in urine.

Front 97

Potassium reabsorption:

Back 97

1. Prox. tubule: Paracellular diffusion from lumen to capillaries. Driving force is the lumen positive transepithelial potential?
2. Loop of Henle: Paracellular diffusion
3. Type a- intercalated cells: At apical surface. H+/K+ antiport---> secreting H+ and reabsorbing K+ increasing ICF K+ cons.---> diffusion into capillaries= increased reabsorption

Front 98

Why Na+ depletion does not lead to increased K+ excretion:

Back 98

↓Na+→ ↓GFR, ↑Na+ reabsorption in prox tubule→ ↓fluid in collecting duct→ ↓K+ secretion in
collecting duct.

Front 99

Potassium regulation:

Back 99

1. Decrease in ECF K+:
- Insulin increase K+ uptake in cells by stimulating Na+/K+ ATPase
- Aldosterone: Increase Na+/K+ ATPase activity in distal tubule and collecting duct increasing K+ excretion
- b- adrenergic stimuli: incr uptake of K+ in cells
- Alkalosis: H+/K+ antiport moves K+ into cells and H+ out

2. Increase in ECF K+:
- Insulin deficiency (diabetes): No stimulation of Na+/K+ ATPase--> decr K+ uptake into cells
- Aldosterone deficiency (Addisons): decr K+ secretion in kidneys
- b- adrenergic blockade: decr K+ uptake into cells
- Acidosis: Increasing intracellular H+ displaces K+ to the extra cellular compartment
- Cell lysis: K+ expulsion from cell
- Strenous exercise
- Increased extracellular fluid osmolarity

Front 100

Concentration and absorption of calcium:

Back 100

ECF cons: 2,4 mmol/L in which 50 % is bound to albumin or phosphates.

99% of calcium is reabsorbed; 65 % in proximal tubule, 25 % in loop of Henle and 10 % in distal tubules. The 1 % excreted matches the 1 % absorbed in the intestines so net secretion is virtually 0!

Calcium reabsorption is stimulated by parathyroid hormone.

Front 101

Renal handling of phosphate:

Back 101

Phosphate reabsorption follows kidneys transport maximum of phosphate. This means if phosphate concentration in filtrate exceeds a certain value, the phosphate transporters get saturated and more phosphate is excreted. PTH decreases transport maximum of phosphate ---> increased PTH---> increased phosphate excretion. PTH also increase bone reabsorption--> increased plasma cons.--> exceeding of transport maximum.

Front 102

Renal handling of AAs and proteins:

Back 102

Most proteins are hindered by the glomerular filter, and rarely enter the urinary space as primary urine. Proteins that do are absorbed in proximal tubule by endocytosis.

AAs are transported from luminal surface by secondary active transport as co- transport with Na+ in proximal tubule, and into blood by facilitated diffusion. down its concentration gradient. Transport maximum of 1,5 mmol/L/ min

A protein rich diet tend to increase Na+ uptake in proximal tubule. This leads to a decrease of Na+ in distal tubule and secretion of renin to counteract a drop in EC Na+.

Front 103

Renin:

Back 103

Enzyme secreted from juxtaglomerular cells (specialized endothelial cells covering efferent arterioles) that converts angiotensinogen to angiotensin I. Release is stimulated by decreased blood pressure in efferent arterioles, decreased filtrate pressure or by decreased Na+ cons. in macula densa cells. The macula densa cells send stimulatory cytokines to juxtaglomerular cells.

Front 104

Action of renin:

Back 104

1. Vasoconstriction
2. Converting angiotensinogen to angiotensin I.
---> angiotensin I is converted to angiotensin II by ACE in lungs which causes vasoconstriction---> increases BP, stimulates thirst, ADH secretion---> Na+ and H2O reabsorption.

Front 105

Erythropoetin:

Back 105

Glycoprotein hormone that stimulates erythropoesis. Is secreted by mesengial cells of juxtaglomerular apparatus stimulated by reduced pO2 in juctraglomerular apparatus.

Erythropoetin stimulates erythropoesis by stimulating hematopoetic stem cells. It also stimulates RBC maturation and hemoglobin synthesis.

Front 106

Calcitriol:

Back 106

AKA 1,25 dihydrocholecalciferol/ vit. D is a cholesterol derivative hormone, which increases plasma Ca concentrations.

Synthesis is regulated by PTH. Synthesized in skin upon exposure to UV- B light. Hydrolyzed in liver to 1- hyroxycholecalciferol, and become 1,25- dihydrocholecalciferol in kidneys.

Action: Increases intestinal absorption of Ca2+ by stimulating transcription of calcium binding protein. Also increases Ca2+ reabsorption in kidney.

Front 107

Composition of urine:

Back 107

1. Metabolites of various hormones
2. Toxins and foreign substances
3. End- products of Hb breakdown (bilirubin)
4. Some dead epithelial cells
5. H2O (96 % of urine)
7. Na+ (150 mmol/day)
8. Cl- (180 mmol/day)
9. Bicarbonate (2 mmol/day)
10. K+ if to high ECF cons.
11. H+ if blood is too acidic
12. Urea (25 g/day)
13. Creatinine (1,8 g/day)
14. Glucose (1g/ 24h)
15. Uric acid (under 10mg/dl- higher leads to gout)
16. Ammonia

Front 108

Bladder anatomy:

Back 108

1. Detrusor muscle that receives parasympathetic innervation.
2. Internal sphincter in neck of bladder. External sphincter surrounds urethra and pierces pelvic diaphragm.
3. Trigone lies posteriorly above neck. Ureters enter in the upper most corners of the trigone.
4. Covered by transitional epithelium that form folds called rugae except in trigone where it is smooth.

Front 109

Bladder physiology:

Back 109

1. Usually hold 400- 650 ml urine, but can hold twice as much without rupturing.
2. Filling: Peristaltic waves transport urine from kidneys to bladder. Intravesicular pressure does not rise even though more urine is present in the bladder, due to intrinsic tone of the bladder.
3. Micturition waves: When volume of urine reaches threshold of 300 ml stretch receptors trigger micturition reflex, which causes contraction of detrusor muscle---> rise in intravesicular pressure---> increasing triggering of stretch receptors (positive feedback)===> in the end the micturition reflex becomes so strong that it inhibits the external sphincter. If inhibition is stronger than voluntary control urination will happen.

Front 110

Autonomic nervous system control over bladder function:

Back 110

Sympathetic innervation from L-2: innervates blood vessels of bladder and relaxes bladder wall.

Parasympathetic innervation from S1- !3. Synapse in ganglionic cells in bladder wall. Innervates detrusor muscle and cause micturition.

Front 111

Micturition:

Back 111

Process by which urinary bladder empties when it becomes filled. Two main steps: 1) The bladder fills until tension in its walls rises above threshold of 300 ml.
2) Nervous reflex called micturition reflex empties the bladder, triggered by stretching of stretch receptors over threshold---> contraction of detrusor muscle---> increase in intravesicular pressure---> increasing of the triggering of stretch receptors (positive feedback) until the micturition reflex becomes strong enough to inhibit the external sphincter---> urination if inhibition is higher than voluntary control of sphincter.