Physiology 9 Flashcards
What purpose does the loop of Henle serve?
To increase the osmolality of the medullary interstitium by extruding ions, presenting a hypotonic tubular fluid to the distal tubule
Where does ion extrusion take place in the loop of Henle?
The thick ascending limb
What are the principle transporters responsible for ion extrusion in the thick ascending loop of Henle?
Basal Na/K ATPase drives the gradient. Secondary active transport of Na+/K+/2CL- across the apical membrane then occurs
What is the maximum medullary tonicity reached due to the action of the loops of Henle?
1400 mOsmol/kg H2O
What is the osmolality of the fluid leaving the loop of Henle?
Approx 90 mOsmol/kg H2O
How is the renal medullary hypertonicity maintained by the collecting duct system?
66% of the fluid delivered to the cortical collecting tubule is absorbed before reaching the medullary CT, delivering less than 5% of filtrate volume and increasing tubular fluid osmolality from 90 to 290 mOsmol/kg H2O.
How does urea concentration of renal tubular fluid change along the length of the nephron?
50% of filtered urea is reabsorbed in the proximal tubule
Urea diffuses into the tubular fluid in the descending loop of Henle down a concentration gradient.
The distal tubule and cortical collecting ducts are impermeable to urea, but water is reabsorbed, increasing urea concentration.
The medullary collecting ducts are permeable to urea, allowing diffusion into the interstitium down a conc. gradient.
How does ADH affect urea transport in the nephron?
ADH, in addition to promoting AQP2 also activates a urea uniporter in the apical and basolateral membranes of the collecting duct cells, facilitating diffusion and maximising interstitial osmolality.
How are the vasa recta affected by countercurrent exchange?
Water is removed and then replaced in the descending and ascending limbs respectively, minimising solute loss.
O2 and CO2 are exchanged between the ascending and descending limbs, making delivery/removal inefficient.
Outline the contribution to concentration of urine that each part of the nephron makes
70% of water is reabsorbed in the proximal tubule
15% is reabsorbed in the loop of Henle
10-15% is reabsorbed by the distal tubules and collecting ducts. This is ADH-dependent.
Outline the synthesis, storage and release of ADH
Synthesised in supraoptic nuclei of hypothalamus and transported to posterior pituitary in nerve fibres for storage.
Osmoreceptors in the supraoptic and paraventricular nuclei regulate release
What plasma level of ADH is associated with a normal osmolality?
4 pg/ml
Outline the function of ADH receptors
ADHR (V2R): G-protein coupled receptors in basal membranes of collecting duct cells. Activation causes increased aquaporin 2 activity at apical membrane
How much urine is produced in 24h in the absence of ADH?
23L per day
What is a normal daily urine volume and osmolality?
1.5L/24h
300-800 mOsmol/kg H2O
Describe the juxtaglomerular apparatus
Early distal tubule comes into close contact with efferent and afferent arterioles. Renin-containing cells in the afferent arterioles and the macula densa of the distal tubule are involved in the RAAS.
What mechanisms lead to renin release?
- Increased sympathetic tone
- Decreased wall tension in the afferent arteriole
- Macula densa stimulates renin release in response to decreased NaCl delivery [poorly understood]
List the actions of angiotensin II
- Stimulates ADH release
- Stimulates aldosterone release
- Increases proximal and distal tubular sodium reabsorption
- Stimulates peripheral vasoconstriction
- Inhibits renin release (-ve feedback)
Where is aldosterone produced?
Adrenal cortex
How important is aldosterone to regulation of ECF volume?
It has a regulatory role, but if release is impaired, other mechanisms can compensate for it.
How does sympathetic stimulation affect blood flow to nephrons?
Constriction of afferent arterioles to superficial nephrons and relative relaxation of afferent arterioles to juxtamedullary nephrons, increasing sodium reabsorption.
Outline the synthesis of prostanoids
Cell membrane phospholipids -> arachidonic acid (by phospholipase A2, PLA2)
Arachidonic acid to TXA2, PGE2 and PGI2 via COX-1
Arachidonic acid to PGE2 and PGI2 by COX-2
In the kidney, which prostanoids predominate in which areas?
Cortex - PGI2
Medulla - PGE2
How are renal prostaglandins related to renal perfusion?
PGE2 and PGI2 vasodilate the renal vessels in response to reduced blood flow, maintaining perfusion
What purpose do renal medullary prostaglandins serve? Why?
as well as vasodilatation, they have a natriuretic and diuretic effect, opposing ADH. This may serve to limit ATP use in reduced ECV situations, protecting against excessive hypoxia
How does ANP affect renal function?
Natriuresis, through:
-Closure of sodium channels and inhibition of Na+/K+ATPase in the inner medullary collecting duct cells
-Inhibition of aldosterone release
-Reduction in renin release
Vasodilatation of afferent arterioles, leading to increased GFR.
Outline the role of dopamine in renal physiology
Synthesised by proximal tubular cells. Inhibits Na+/K+ ATPase and Na+/H+ antiport activity.
What receptor mediates sympathetic renin release?
Beta receptors
How is the distal tubule involved in acid-base balance?
HCO3- (10%) is reabsorbed in the same way as the proximal tubule.
H+ ions are secreted by an H+ ATPase pump and an H+/K+ ATPase. Na+/H+ transport also occurs but is has less impact
How does the ratio of phosphate conjugates change through the nephron
Plasma alkaline PO4:acid PO4 4:1, this reduces along the nephron, mainly in the distal tubule due to H+ secretion and Na+ absorption
How is the ammonium buffer produced in the nephron?
Deamination of glutamine in the tubular cell produces NH4+
2-oxoglutarate reacts with H+ to form glucose or CO2 (and thus bicarb)
NH4+ is secreted into the tubule
What would happen if renal tubular NH4+ were not secreted?
Ammonium would be metabolised by the liver to urea, using HCO3- as a substrate, negating the renal production of bicarb. Thus NH4+ secretion is closely linked to HCO3- production
How is ammonium treated distal to the proximal tubule?
NH4+ reabsobed in the thick ascending loop of Henle via Na+/NH4+/2Cl- cotransport.
It is then secreted back into the tubule by collecting duct cells (as H+ and NH3 which combine in the lumen)
Why does NH4+ excretion increase in acidosis?
- Enzymes which deaminate glutamine are stimulated by acidosis
- Increased H+ secretion maintains a NH3 gradient in the collecting duct, removing more NH3/NH4+ from the medulla
What is the normal partial pressure of inspired oxygen for room air? (PiO2)
PiO2 = 21.2 kPa (159.2 mmHg)
What is the normal partial pressure of oxygen in alveolar gas in room air? (PAO2)
PAO2 = 14 kPa (10.5 mmHg)
What is the normal partial pressure of oxygen in arterial blood in room air? (PaO2)
PaO2 = 13.3 kPa (100 mmHg)
What is the normal partial pressure of oxygen in mixed venous blood in room air? (PvO2)
PvO2 = 5.3 kPa (40 mmHg)
Outline the functional anatomy of the thoracic airway
- Conducting zone - Generations 1-16 (trachea to terminal bronchioles). Volume 150ml. Functions are bulk flow during inspiration/expiration and warming and humidification of inspired air
- Respiratory zone - Generations 17-23 (respiratory bronchioles to alveolar sacs). Volume 3000ml. No bulk flow - gases move by diffusion down concentration gradient. Function is gas exchange.
What are the main factors affecting alveolar gas exchange?
- Dead space
- Diffusing capacity
- Shunt
Outline the concept of dead space
-Anatomical dead space: Upper airway, nose, pharynx, conducting zone.
Alveolar minute ventilation can be calculated - AMV = (TV - DSV) x RR
-Alveolar dead space: The proportion of AMV that is not exchanging gas at maximum capacity eg. due to underperfusion.
Outline the concept of diffusion capacity. What are the relevant variables?
The volume of a gas that can be transferred across a membrane per unit time.
Variables are:
- Alveolar surface area
- O2 diffusion constant
- Thickness of alveolar and capillary membrane
- Diffusion gradient
Define Fick’s Law
Diffusion of a gas ∝ A/T x D (P1-P2)
A - surface area T - thickness of membrane D - diffusion constant (solubility/sqroot molecular weight) P1 - partial pressure in alveolus P2 - partial pressure in capillary
What is a normal oxygen alveolar uptake at rest?
250 ml/min
How fast does O2 equilibrate across the alveolus in normal circumstances?
0.25 secs
What is RBC transit time through an alveolar capillary?
0.75 secs
Outline the concept of shunt
Divided into normal/pathological and pulmonary/extrapulmonary
Normal pulmonary shunt: Areas of lung where V/Q > 0 and <1
Normal extrapulmonary shunt: Venous return from thebesian circulation
Pathological pulmonary shunt: eg. atelectasis, pneumonia
Pathological extrapulmonary shunt: eg. cyanotic heart disease
Define the terms shunt and venous admixture
Shunt: The total proportion of blood entering the LEFT heart which has bypassed oxygenation in the pulmonary circulation
Venous admixture: The amount of mixed venous blood you would have to add to pulmonary end capillary blood to produce the observed difference between PAO2 and PaO2
What is a normal V/Q ratio? How is this calculated?
0.8
AMV / CO
4000 ml / 5000 ml = 0.8
How is inspired PO2 calculated?
PIO2 = FiO2 x (PB - PH2O)
PB = barometric pressure PH2O = SVP of water at 37°C
(alveolar air is fully saturated at 37°C)
What is the SVP of water at 37°C?
6.3 kPa
