EXAM III Flashcards
What are the components of glomerular filtration and what is the fraction of renal plasma flow that’s filtered?
Water
Ions
Glucose
Urea
0.2 ~ 20%
Filtration fraction = GFR/Renal plasma flow
Molecules w/ (+) charge gets filtered while (-) is repelled and stays in blood; hence why Na+ is mainly the driving force
What are the components that make up the glomerulus?
Podocytes = filtration slits
Pedicelles
Basement membrane
Fenestrated capillaries
What are the layers of the filtration barrier?
Endothelium - w/ fenestrae & (-) charges
Basement membrane - w/ collagen & proteoglycan fibers and strong (-) charges
Podocytes - with (-) charges
What is GFR determined by?
The balance of hydrostatic and colloid osmotic forces acting across capillary membrane (i.e. Starling forces)
The capillary filtration coefficient (which depends on the leakiness of the capillaries and the number and size of pores) K1 - product of permeability and filtering SA of capillaries
Albumin is slightly smaller than filtration pores but have (-) charges
What is the normal GFR?
125 ml/min = 180 L/day
(water has a filterability o = 1.0)
What are the active forces in GFR?
Pg - glomerular hydrostatic pressure
Pb - Bowman’s capsule hydrostatic pressure
πg - glomerular capillary colloid osmotic pressure
πb - Bowman’s capsule colloid osmotic pressure
GFR = K1 x (Pg - Pb - πg + πb)
GFR = K1 x Net filtration pressure
What is K1 and describe how this value alters GFR
Capillary filtration coefficient - product of permeability and filtering SA of capillaries
Hight K1 = high GFR
Low K1 = lower GFR
What are the factors that influence glomerular capillary colloid osmotic pressure? (2)
Arterial plasma colloid osmotic pressure
Filtration fraction (how much blood is actually being filtered)
What are factors that increase glomerular colloid osmotic pressure?
Increasing the filtration fraction
What are the variables that determine glomerular hydrostatic pressure? (3)
Arterial Pressure (pressure going to the glomerulus)
Increases = greater Pg –> increase GFR
Afferent arteriolar resistance
Increase –> less PG –> less GFR
Efferent arteriolar resistance
Increase –> greater PG –> slightly greater GFR
What are the factors that determine renal blood flow?
Renal artery pressure
Renal vein pressure
Total vascular resistance
Renal blood flow = renal art. p-renal vein p./total vasc. resistance
Contains a high rate of Na+ reabsorption, which is related to GFR and rate of Na+ filtered, related to active transport
Kidneys ahve 7x the blood flow of the brain but only 2x O2 consumption
Kidney O2 consumption related to high rate of active Na+ reabsorption
What are the effects of the sympathetic NS on kidneys?
Strong activation:
Constrict renal arterioles
Decrease renal blood flow and GFR
Moderate activation: little effect
What hormones are involved in controlling GFR consistency?
NEpi and Epi (adrenal medulla)
Endothelin
Angiotensin II
Endothelial-derived NO
Prostaglandin and Bradykinin
How does Endothelin work to help control GFR consistency and when is it released?
Released by damaged vascular endothelial cells of the kidneys and other tissues
May contribute to renal vasoconstriction = reduced GFR
May contribute to hemostasis
Plasma levels may increase in toxemia of pregnancy, acute renal failure, and chronic uremia
How does Angiotensin II work to help control GFR consistency?
Increases GFR by constricting efferent arterioles
Usually formed during decreased arterial pressure or volume depleting
Afferent arterioles seem to be protected against the effects of angiotensin II due to NO and prostaglandin release (vasodilators)
How does Nitric Oxide work to help control GFR consistency?
Basic levels helps maintain renal vasodilation
Dervied from endothelial cells
How does Prostaglandins and Bradykinin work to help control GFR consistency?
Vasodilators which may offset effects of sympathetic and angiotensin II vasoconstrictor effects (esp. on afferent arterioles)
Define autoregulation and state its primary function
The relative constancy of GFR and renal blood flow
Primary function = Maintain a relatively constant GFR
Allow precise control of renal excretion of H2o & solutes
Prevent relatively large changes in GFR & renal excretion that would otherwise occur w/ changes in BP
If no autoregulation were to occur in the kidneys, how high can GFR and urine flow increase?
GFR up to 225 L/day (normal 180 L/day)
Urine flow = 46.5 L/day (normal 1.5 L/day)
What is the tubuloglomerular feedback mechanism for autoregulation? What are the components?
Afferent arteriolar feedback mechanism
Efferent arteriolar feedback mechanism
What is the juxtaglomerular complex and where is it?
Next to the glomerulus
Macula dense in distal tubule
Juxtaglomerular cells in afferent & efferent arterioles
(involved in autoregulation)
What is occurring during autoregulation when there is a decrease in GFR, causing a slow rate in loop of Henle? (macula densa)
Increase reabsorption of Na+ and Cl- ions in ascending limb
Decrease NaCl at macula densa
What mechanism occurs during autoregulation when there is a decrease in [NaCl], resulting in a signal from macula densa?
Decrease resistance to blood in afferent arterioles
Increase renin release from JG cells (major storage site of renin)
Increase in angiotensin II
Increase in efferent arteriolr resistance
How must a substance be reabsorbed? What 2 routes can they undergo?
Across tubular epithelial membrane –> renal interstitial fluid –> thru peritubular capillary membrane –> blood
via
Paracelluar (b/w cells) or Transcellular (thru cells) routes via osmosis
Paracellular transport via Ca2+/Mg2+ due to lumen being (+) charged
What are the 3 aquaporins that transport water?
Which one is controlled by ADH? What are their locations
AQP:
Aquaporin-1 = widespread including renal tubules
**Aquaporin-2 - apical membranes of collecting tubule cells; controlled by ADH
Aquaporin-3 - basolateral membranes of collecting tubule cells
What substance should NOT be filtered into the filtrate?
Proteins
also Albumin; albumin is small but carries a (-) charge
Other small substances are not freely filtered because they are partially bound to proteins
What are the channels that are found in nephrons?
ENaC channel (NaCl channel)
found in apical membrane of nephron cells
CFTR (Cl-) and K+ channels found in apical membranes of some nephron segments
Uniporters - driven by [gradient] of [substance]
What type of transport involves the movement of glucose transport?
Facilitated transport
What are the primary active transporters that are involved in the nephron?
Na+K+ATPase
H+ATPase
H+K+ATPase
Ca2++ATPase
What type of channels are involved in secondary active transport?
Na+-glucose co-transporters on brush border of proximal tubule cells
SGLT1 - reabsorbs 10% of glucose in late PCT
SGLT2 - reabsorbs 90% glucose in early PCT
Aminio acids are also involved in secondary active transport
List the main substances that the proximal tubule reabsorbs
65% of filtered Na+, Cl-, bicarbonate, K+
Gluocose
Amino acids
(great amount of [H+} in lumen via Na+ antiport transport; forming carbonic acid w/ luminal bicarbonate via carbonic anhydrase)
List characterstics of the thin descending segment of the LOH
Highly permeable to water; reabsorbs ~20% of filtered H2o
Moderately permeable to most solutes; urea and Na+
What are the characteristics of the thick ascending LOH?
Impermeable to water
Na+K+ATPase pump in basolateral membranes (driving K+ reabsorption against [gradient])
Na+,K+, 2Cl- co-transporter
K+ leak into lumen
Paracellular transport = Mg2+, Ca2+ into interstitial fluid due to K+ leak causing a (+) charge
Where along the nephron does the macula densa begin to form?
Early distal tubule
What are the characteristics of the distal tubule (channels)?
Na+Cl- co-transporter (luminal membrane)
Na+K+ATPase pump (basolateral membrane)
Impermeable to H2o and urea
Diluting segment
What are the basic functions of the principal cells?
Reabsorb Na+ and H2o from tubular lumen
Secrete K+ into tubular lumen
Na+K+ATPase pump
Primary site of K+ sparing diuretics
What are the functions of the alpha-intercalated cells of the late distal tubule/cortical collecting tubule?
Reabsorb K+ from tubular lumen
Secrete H+ into tubular lumen via H+ATPase transporter; H+ generated via carbonic anhydrase
Characteristics of the medullary collecting duct
Cuboidal epithelial cells w/ few mito
Controlled by ADH (which insert aquaporins 2)
Permeable to urea; Urea transporters
Capable of secreting H+ against a large [gradient]
Where is the site of action for aldosterone?
Principle cells of cortical collecting ducts
Increases Na+ reabsorption and K+ secretion
Which hormone is involved with Addison’s disease? What is the problem?
Aldosterone
Loss of Na+ and accumulation of K+
What hormone is Conn’s syndrome related to?
Aldosterone
Hypersecretion of aldosterone
Which hormone is released due to an increase in extracellular potassium and increased levels of angiotensin II?
Aldosterone
via adrenal cortex
What is the function of Angiotensin II?
Increases Na+ and water reabsorption and returns BP and extracellular volume toward normal
What are the effects of angiotensin II?
Stimulates alderosterone secretion
Constricts efferent secretion
Directly stimulates reabsorption in proximal tubules, LOHs, distal tubules, and collecting tubules
What are the effects of ADH?
Binds V2 receptors in late distal tubules, collecting tubules, and collecting ducts
Increases formation of cAMP by stimulating movement of aquaporin-2 proteins to luminal side of cell membranes
What is the source of ANP and what response causes its release?
Cardiac atrial cells
In response to distention
Function: Inhibits reabsorption of Na+ and H2o
What is the source of parathyroid hormone and what is its function?
Parathyroid gland
Increases Ca2+ reabsorption
What are the 2 circulations of the lungs? List the pathway
High pressure; Low flow
Thoracic aorta -> bronchial arteries -> trachea, bronchial tree, adventitia, CT
Low pressure; High flow
Pulmonary artery & branches -> alveoli
pulmonary arteries 1/3 thickness or aorta = larger compliance; 7mmHg (accommodates SV output of right ventricle)
What is the result when you have failure of left side of the heart?
Pressure build up in pulmonary circulation
Increases blood volume as much as 100%
Increases blood pressure
Mild systemic affect bc systemic blood volume is 9x that of the pulmonary system
What is the physiologic shunt? What does it result in?
Also called venous admixture/wasted blood flow
Blood entering the arterial system without passing through ventilated areas of lung causing the PO2 of arterial blood to be less than that of alveolar PO2.
Blood from LA wall that dumps directly into LA
About 2% of blood in systemic arteries is blood that’s bypassed pulmonary capillaries
What are the 3 zones of the lungs?
Zone 1 - no blood flow; local alveolar capillary pressure never rises higher than alveolar air pressure
Zone 2 - Intermittent blood flow (only during systole)
Zone 3 - Continuous blood flow
The lung apices (apex) have which zone flow?
Zone 1
Zone 2
Zone 3
Zone 2; lower areas have zone 3 flow
In standing position, more blood flows to the base/bottom of lungs
The base of the lungs have which zone flow?
Zone 1
Zone 2
Zone 3
Zone 3; while standing, as much as 5x more blood flows to the base of the lungs rather than the apex
What is the normal effect of exercise on the apices of the lung?
Converts them from zone 2 to zone 3
What are the agents that constrict pulmonary arteries?
NEAP - No Erin Acts Pretty (as me)
Epi
NEpi
Angiotensin II
Some Prostaglandins
What occurs during heavy exercise leading to the increase in blood flow?
Increases # of open capillaries up to 3x
Distends all capillaries and increases flow rate up to 2x
Increases pulmonary arterial pressure
Why doesn’t the pulmonary arterial presure rise durnig max exercise?
Due to an increase in opened capillaries and distended capillaries; increasing flow rate
This method converves energy of right side of the heart and prevents sig. rise in pulmonary capillary pressure
What are the 4 things that occur during left-sided heart failure?
Blood begins to damn up in LA
LA pressure rises to 40-50mmHg
Increases above 8mmHg cause equal increases in pulmonary arterial pressure
Above 30mmHg = pulmonary edema likely to develop
What are the most common causes of pulmonary edema and at what capillary pressure level does it occur?
Left-sided hearth failure or mitral valve disease
Damage to pulmonary blood capillary membrane via infections or breathing noxious substances
Lethal pulmonary edema can happen = minutes/hours
> 25 mmHg
How does hypoxia effect blood flow in the pulmonary system?
Increases pressure in the pulmonary artery
Possibly due to release of a prostaglandin
What are the results of bronchial obstruction in relation to blood flow? What are the causes?
Constriction of vessels supplying the poorly ventilated alveoli
Due locally to low alveolar PO2 effect on the vessels
pH drop due to CO2 accumulation
pH drop causes vasoconstriction in pulmonary vessels
pH drop produces vasodilation in other tissues
What is the result of reduction of blood flow to a portion of the lung?
Lowers alveolar PCO2
Resulting in a constriction of the bronchi supplying that particular portion of the lung
What are the major components in the air and what are their relative concentrations?
N = 78%
O2 = 20.95%
Ar = 0.93%
CO2 = 0.03%
Define Dalton’s Law
The total pressure exerted by the mixture of non-reactive gases is equal to the sum of the partial pressures of individual gases
Define Boyle’s Gas Law
For a fixed amount of an ideal gas kept at a fixed temperature, pressure and volume are inversely proportional
P1V1 = P2V2
Define Henry’s Gas Law
At a constant temperature, the amount of a given gas that dissolves in a given type and volume of liquid is directly proportional to the partial pressure of that gas in equilibrium with that liquid
PP = [dissolved gas]/sol. coefficient
O2 solubility = 0.024
CO2 solubility = 0.57
T/F
CO2 is more soluble in water than O2; explain this concept
True
Due to this, CO2 exerts a partial pressure (for a given []) that is less than 1/20th that of oxygen
What are the factors that control oxygen concentration in the alveoli?
Rate of absorption of oxyen into the blood
Rate of new oxygen entry into the lungs (alveolar ventilation)
What is normal GFR?
125 ml/min ~ 180 L/day
What is the amount of daily normal fluid excretion?
1.5 L/day
What would GFR be without autoregulation? How high would this increase urine flow?
225 L/day
Urine flow up to 46.5 L/day
What percentage of filtered Na+, bicarbonate, K+, glucose, and aa is reabsorbed in the PCT?
65%
How is Na+ reabsorbed in the first and second 1/2 of the PCT?
First 1/2 = Co-transporter; w/ glucose and amino acids
Second 1/2 = via Cl- ions
What is the H+ and Bicarbonate ion association in the PCT? What is occurring?
Na+ and H+ are transported via antiporter mechanism
[H+] is increasing in the tubular lumen and combines with luminal bicarbonate to yield water and CO2
H+ + HCO3- –> H2CO3 –> CO2 + H2O
CO2 diffuses into tubular cell to combine with water and eventually forming H+ and new bicarbonate which is excreted
What are the characteristics of the early distal tubule?
Na+Cl- ATPase symporter into the tubular cell; apical membrane
Basolateral membrane: Na+/K+ ATPase
(similar to thick ascending LOH)
What are the events that are happening in the late distal tubule? Transporter types, cell types, etc.
Intercalated Cells (H2o impermeable)
Apical - H+/K+ ATPase (K+ reabsorbed, H+ excreted), H+ ATP pump (excreted)
H+ joins NH3 to form NH4, H+ is coming from bicarbonate CA system
Basolateral - Na/K ATPase, K+ leak
Principal Cells = ADH action, K+ sparing diuretics (H2o impermeable)
Apical - Aquaporins, Na+, K+ leaks
Basolateral - Na/K ATPase
T/F
Collecting Duct is permeable to urea
Collecting duct contains many mitochondira
TRUE - permeable to urea
FALSE - contains few mitochondira
What are the hydrostatic and osmotic forces involved in lung capillary fluid exchange? How is excess fluid carried away?
Outward Forces:
Pulmonary capillary pressure
Pulmonary Interstitial fluid colloid osmotic pressure
Pulmonary Interstitial fluid hydrostatic pressure
Inward Forces:
Pulmonary capillary osmotic pressure
Excess fluid is carried away via pul. lymphatics
At what pressures do the lungs tend to collapse?
When pressure becomes more positive
i.e. greater than -7 mmHg
Can occur during pleural effusion = edema of pleural cavity
Explain why alveolar ventilation cannot increase PO2 above 149 mmHg under normal conditions
Due to part pressure of oxygen in the atm
FRC of lungs = 2300ml
350 ml of new air is brought into alveoli w/ each normal inspiration and the same amount is expired
Multiple breaths are required to exchange most of alveolar air
Only 1/7 is replaced by new atm air
What are the factors that control CO2 concentration in the alveoli?
Rate of CO2 excretion
Alveolar PCO2 increases in direct proportion to rate of excretion
Alveolar Ventilation
Alveolar PCO2 decreases in inverse proportion to alveolar ventilation
Graphs: Lines = rates of excretion
What are the components of the respiratory membrane?
Basement membrane of the capillary
Basement membrane of the epithelium of the alveoli
(Interstitial space sometimes present)
What does the Va/Q ratio refer to?
Ventilation-Perfusion Ratio
The ratio of alveolar ventilation and blood flow
Normal = 0.8
Normal Va/Q when both pulmonary and ventilation factors are normal (pulmonary = 5 L/min; ventilation = 4 L/min)
What is the normal Va/Q ratio?
0.8
What happens to the Va/Q ratio when there is an airway obstruction?
Va = 0; Perfusion still occurs
Gas levels equilibrate throughout system
Blood gas composition remains unchanged
What happens to the Va/Q ratio when there is a vascular obstruction? What are the alveoli partial pressure values?
i.e. pulmonary embolism
Ventilation still occurs; No perfusion; Va = infiniti
No blood contact creating a physiologic shunt
PO2 = 149 mmHg; PCO2 = 0 mmHg
Define Shunted Blood
Blood that does not become oxygenated due to having a Va/Q ratio below normal.
Define Physiological Shunt
Wasted Blood Flow
Due to blood entering arterial system that does not pass through ventilated areas, causing PO2 of arterial blood to be less than alveolar PO2
Define Physiological Dead Space
The sum of wasted ventilation plus anatomic dead space
Wasted ventilation
Due to having a greater amount of ventilation with low perfusion
How much water can be excreted by the kidneys per day when there is a large excess of water in the body?
Forms dilute urine
20 L/day w/ 50 mOsm/L
Kidney reabsorbs solutes and NOT water
Ascending LOH reabsorbs Na+, K+, Cl-
Late DCT reabsorbs Cl-
What is required by the kidney tubules for the formation of concentrated urine?
Requires ADH
and high osmolarity of renal medullary interstitial that creates an established gradient
What is the max urine concentration that the kidneys can produce? What’s required by the kidney tubules for this to occur?
1200-1400 mOsm/L
ADH must be present so that you can keep the water and make urine concentrated
High osmolarity or the renal medullary interstitial tubule which establishes an osmotic gradient that’s necessary for water reabsorption to occur
How much volume of solute must be excreted per day and why must this occur?
~600 mOsm
To rid of waste products of metabolism and ions that are ingested
Where in the kidney tubule are most of the filtered electrolytes reabsorbed?
PCT
What is the role of the osmoreceptor-ADH feedback mechanism? What is happening during this mechanism?
Controls extracellular fluid [Na+] and osmolarity
An increase in [Extracellular-fluid osmolarity] causes a shrinkage of osmoreceptor cells in anterior hypothalamus which creates an Action potential which releases ADH = increases water permeability in distal nephron segments
Where specifically is ADH formed?
Magnocellular neurons in the
Supraoptic nuclei
Paraventricular nuclei
Osmoreceptor cells
What is the normal [extracellular K+ ion]? What is the clinical significance of excess extracellular K+?
normal = 4.2 mEq/L
An increase can can cardiac arrhythmias (3-4 mEq/L)
An even greater increase can cause cardiac arrest or fibrillation
What is the overall affect of aldosterone on potassium excretion?
Levels increase potassium secretion
What factors stimulate principal cells to secrete K+?
Increase in extracellular K+ levels
Aldosterone effects
What effects do insulin and catecholamines have on extracellular K+ levels?
Insulin - stimulates K+ uptake/reab. which increases intracellular K+ and decreases extracellular K+
This in turn causes Aldosterone to increase which will increase K+ secretion to reduce the intracellular levels of K+ (via increased function of Na+/K+ ATPase pumps and luminal membrane permeability)
Catecholamines i.e. Epi (beta-adrenergic) = stimulates cellular K+ uptake
Beta-adrenergic blockers = hyperkalemia (extracellularly)
Which buffer system is most important in extracellular space? Intracellularly?
Bicarbonate buffer system = weak acid and bicarbonate salt
Intracellularly = Phosphate buffer system = major flow in renal tubular flow
Define buffer
A substance that can reversibly bind H+ that contains a weak acid
What organ primarily regulates the bicarbonate buffer system?
Kidneys
Excretes HCO3-
What is the primary method for removing nonvolatile acids?
Renal excretion
What must happen before filtered bicarbonate is reabsorbed?
Reacts with secreted H+ ions to form carbonic acid
What is the lower limit of pH that can be achieved in normal kidneys?
4.5
