Physiology Flashcards
1
Q
define osmolality
A
concentration of osmotically active particles present in a solution
2
Q
how is osmolality calculated
- 150mM NaCl
- 100mM MgCl2
A
3
Q
what is the normal osmoraltiy of body fluids
A
285-295 mosmol/L
4
Q
define tonicity
A
the effect a solution has on cell volume
- Hypotonic solutions have a lower osmolality, and so more water. Cause cell lysis as water diffuses in by osmosis.
- Isotonic solutions don’t change cell volume
- Hypertonic solutions have a higher osmolality, cause cells to shrink
5
Q
what else is tonicity influenced by
A
the ability of a solute to cross the cell membrane
6
Q
compare total body water of male and female
A
females have less as they have more fat cells which contain little water
7
Q
which tracer can be used to measure TBW
A
trihydrate
8
Q
which tracer can be used to measure ECF
A
inulin
9
Q
which tracer can be used to measure plasma
A
labelled albumin
10
Q
sensible and insensible losses of fluid
A
insensible are those over which there is no physiological control
11
Q
average composition of ECF
A
- Na 140mM
- Cl 115mM
- HCO3- 28mM
12
Q
Average composition of ICF
A
K - 140mM
13
Q
how are the ECF and ICF separated and compare the osmotic concentrations
A
- separated by a semi permeable memrbane
- the osmotic concentrations are the same
14
Q
how does a gain in NaCl affect the ECF and ICF
A
- isotonic fluid
- results in a change in ECF volume only as it does not affect fluid osmolality
15
Q
where it the majority f sodium lost
A
mainly from urine
16
Q
what is an importnat role of K
A
establishing membrane potential
17
Q
compare the body weight of kidneys and the CO they recieve
A
- 25% CO
- 0.5% body weight
18
Q
what is the functional unit of the kidney
A
the nephron
19
Q
describe the blood supply of the kidney
A
- cortical - peritubular capillaries
- juxtamedullary -vasa recta
20
Q
how many nephrons does one collecting duct recieve input from
A
multiple
21
Q
what is different about juxtamedullary nephrons
A
- they have a longer loop of Henle which descends further down into the medulla
- therefore produce a more concentrated urine as are exposed to more of the multiplying concentration gradient
- have a single vasa recta instead of multiple peritubular capillaries
22
Q
function of mesangial cells
A
- provide support to capillaries
- regulate blood flow throughthem by controlling contractile status
23
Q
granular cells - location and function
A
- modified smooth muscle cells inthe walls of the afferent arteriole
- secrete and produce renin
24
Q
macula densa
A
- Macula densa is an area of closely packed cells lining the wall of the distal tubule
- senses Sodium concentration as the tubular fluid passes through that region of the nephron
25
what is urine
a modified filtrate of blood
26
what percentage of plasma entering the glomerulus is filtered
20%
27
define rate of excretion
* **Rate of excretion = rate of filtration + rate of secretion – rate of reabsorption**
* **Rate of excretion** of X is the mass excreted per unit time: [X]urine x Vu
28
rate of filtration
* mass of X filtered into the Bowman’s capsule per unit time, for a freely filterable substance X: [X]plasma x GFR
29
what is the outer layer of Bowman's capsule formed from
a single layer of simple squamous epithelium
30
what does the glomerular capillary enodthelium act as a barrier towards
RBCs
31
describe the basement membrane
* acellular and composed of collagen and glycoprotein
* net negative charge which repels negatively charged plasma proteins
* plasma protein barrier
32
podocytes
33
is filtration passive or active
entirely passive
34
outline the Starling forces involved in filtration
NFP = 10mmHg
35
what is the oncotic pressure of Bowman's capsule
0, no plasma proteins
36
define GFR
* The rate at which protein-free plasma is filtered into Bowman’s capsule per unit time
* **= Kf x NFP**
37
what is Kf
the filtration coefficient - how holey the glomerulus is
38
which straling force is the major determinant of GFR
* The BPGC is the major determinant of GFR, as it is the largest in terms of magnitude
39
extrinsic regulation of GFR - sympathetic control via baroreceptor reflex
* In situations of falling blood volume, carotid and aortic baroreceptors stop firing, allowing uninhibited sympathetic activity. Respond to stretching (increased blood pressure and volume) by inhibiting sympathetic activity.
* Adrenaline from the adrenal medulla acting on alpha 1 receptors causes vasoconstriction of afferent arterioles (smooth muscle in walls)
* This decreases the blood flow into the glomerulus, decreasing BPGC, and decreasing NFP, and GFR. Results in a decrease in urine volume.
40
how is GFR protected from short term changes in MABP
* autoregulation - intrinsic control (no hormones)
* helps eg maintain water and salt balances in exercise - MABP inc but want to retain fluid
* **myogenic**: If vascular smooth muscle of afferent arteriole is stretched by increased arterial pressure it responds by contracting, thus constricting the arteriole
* **Tubuloglomerular feedback:**
* If GFR rises, **more NaCl** flows through the tubule leading to **constriction** of the afferent arterioles
* Increased Sodium in the tubular fluid is sensed by the macula densa causes the release of adenosine, which causes vasoconstriction
* This is a negative feedback mechanism
41
how does diarrhoea affected COP of the glomerular capilllary
increases it - decreased GFR
(lost water so plasma proteins are now in greater concentation)
42
causes for decreased COP of the glomerular capillary
* burns - loss of plasma proteins from site of injury
* increased GFR
43
how does a kidney stone effect GFR
increased hydrostatic pressure of Bowman's capsule - dec GFR
44
define plasma clearance
* a measure of how effectively the kidneys can clean the blood of a substance
* **Clearance of substance X = rate of excretion of X** ([X]urine x Vu) **/ plasma concentration of X**
45
inulin
* neither secreted or reabsorbed in the tubules - measure of GFR
* not conveient though as patient must be hooked up to IV line as it is exogenous substance
46
calculate GFR from inulin
47
what is now used to measure GFR
creatinine - endogenous substance
48
production of creatinine
* produced at a constant rate
* slight tubular secretion - approx GFR
49
name 2 problems with creatinine
* creatinine is not sensitive to changes in GFR until it is quite low, at which point most patients swill already have presented for clinical reasons
* muscle mass and diet are proxies for age, sex and ethnicity - influenced by amount of urine creatinine and volume of urine
* marker of skeletal muscle breakdown
50
eGFR
* estimated GFR, calculated on patient's age, sex, race and serum creatinine
* better
51
shortfall of eGFR
not very accutate \>60ml/min - anything above this is reported as just that
52
53
glucose
* Filtered, completely reabsorbed and not secreted
54
urea
* Filtered, partially reabsorbed and not secreted - clearance
not produced at a constant rate
55
H ions in the tubules
* Filtered, secreted and not reabsorbed
* **Clearance \> GFR = secreted**
56
what is used to calculate renal plasma flow
* para-amino hippuric acid
* PAH is freely filtered at the glomerulus, secreted into the tubule from the capillary and completely cleared from the plasma (e.g. all the PAH that escapes filtration is secreted from the peritubular capillaries)
* RPF is usually around **650 ml/min**
57
define renal plasma flow
* volume of blood plasma delivered to the kidneys per unit time
58
osmolality of fluid in filtrate and proximal tubule
the same - there is no change in osmolality between the start and end of PT as water and salt are absorbed in equal proportions
59
what is reabsorbed in the PT
* Sugars -100%
* Amino acids – 100%
* Phosphate
* Sulphate
* Lactate
* Urea
60
what is the wall of the tubule formed by
single layer of epithelial cells
61
define facilitated diffusion
passive carrier mediated transport of a substance down its concentration gradient
62
sodium reabsorption in the PT
* Na+ reabsorption is driven by the **Na+ K+ ATPase pump** at the basolateral membrane. This pump is exclusively expressed here
* Sodium drives the secretion of hydrogen ions across the apical membrane
* The net movement of sodium sets up an **electrochemical gradient** for the net reabsorption of **chloride ions** across the paracellular route
* This sets up an **osmotic gradient**, down which **water** follows paracellularly
* The **plasma proteins** in the capillary (which are in greater concentration as the capillary has 20% less volume due to glomerular filtration) exert an **oncotic drag** which pulls the fluid into the peritubular capillary
63
howb much glucose does each transporter reabsorb
* 90% through SLGT2 in S1
* the rest through SGLT1 in S3
64
glucose reabsorption in PT
* Normally, 100% of glucose is reabsorbed in the proximal tubule
* It crosses the apical membrane by a secondary active transporter (SGLT1 and 2), and then crosses the basolateral membrane down its concentration gradient by facilitated diffusion
* The movement of glucose sets up an **osmotic gradient for water** to follow paracellularly
65
transport maximum for glucose
2mmol/min
66
what is the function of the loop of Henle
to generate a cortic-medullary solute concentration gradient which enables the formation of hypertonic urine in the presence of ADH
67
what is the name for the opposing flow int he two limbs of loop of Henel
countercurrent flow
68
how is NaCL reabsorbed inthe thick and think ascending loop
* active in the thick
* passive in the thin
69
compare the osmolality of fluid leaving the LoH to that entering it
osmolality decreases
70
Na transport in the thick ascending loop of Henle
* TALH triple cotransporter pumps ions out of the lumen of the loop of Henle
* 2 Cl ions, 1 Na and 1 K. This creates an electroneutral transporter
* K+ recycling at apical and basolateral membrane allows for NaCl to be reabsorbed into the interstitial fluid
71
urea cycle in the kidney
The **urea cycle** also contributes to approximately half of the medullary osmolality. The distal tubule is not permeable to urea. The collecting duct absorbs around 50% of urea, which diffuses passively into the loop of Henle. **Urea adds solid to the interstitium.**
## Footnote
**two solute hypothesis**
72
what forms a counter current system
The vasa recta act as a **countercurrent exchanger,** and together, the loop of Henle and vasa recta form a **countercurrent system.**
73
how do JM nephrons minimise the problem of blood flow washing away NaCl and urea
* Following hairpin loops
* Freely permeable to NaCl and water
* Low blood flow in comparison to the flow in the renal cortex
this preserves the CM gradient as blood equilibrates at each layer, as well an ensuring that solute is not washed away
74
in summary what makes the medullary osmotic gradient, and what preserves it
* The countercurrent multiplier and the urea cycle create the medullary osmotic gradient
* The countercurrent exchanger preserves that gradient
75
synthesis of ADH
An octapeptide that is synthesised in the hypothalamus in neuron cell bodies. It is transported down neuron axons to nerve terminals in the posterior pituitary gland, where it is stored in granules.
76
what is the most important stimulus for ADH release
hypothalamic osmoreceptors
77
halflife of ADH
peptide hormone - 10-15 minutes
78
ADH mechanism
* acts on vasopressin receptors 2
* inserts new aquaporin channels into the luminal membrane
* water moves down its concentration gradient into the medullary interstital fluid, enabling the formation of hypertonic urine
* acts on the distal tubule and collecting duct
79
ADH on vasopressin receptor 2: when will water stop moving across
Water continues to be reabsorbed along its osmotic gradient until osmotic equilibrium is restored.
80
what happens in the distal tubule in the presence of minimal ADH
In the presence of **minimal ADH concentration** in the plasma, the AQP have become internalized and the distal tubule and collecting ducts are no longer permeable to water.
81
ADH vasoconstrictor effect
ADH binds to V1 on vascular smooth muscle to cause vasoconstriction, which increases arterial pressure.
82
role of ADH in severe hypovolemic shock
* In cases of e.g. severe hypovolemic shock, ADH release is very high and contributes to the compensatory increase in systemic vascular resistance
* Hypovolemia results in a decrease in atrial pressure, which is sensed by specialized stretch receptors within the atrial walls and large veins (cardiopulmonary baroreceptors) entering the atria decrease their firing rate when there is a fall in atrial pressure
* Atrial receptor firing normally inhibits the release of ADH, this leads to increased ADH release.
83
name another system that release ADH
* Increase in angiotensin II stimulates ADH release (RAAS)
84
nicotine, alcohol and ecstacy effect on ADH release
* Nicotine stimulates ADH release
* Alcohol and ecstasy inhibit ADH release
* this is why you can get dehydrated cos you are not concentrating your urine (people can die from drinking too much water when on ecstacy)??
85
ADH in heart failure
* Heart failure is associated with a paradoxical increase in ADH, increased blood volume and atrial pressure should decrease ADH secretion, but they do not
* this may be due to an abnormal increase in RAAS due to decreased CO and BP
86
what effect does decrease renal blood flow have on EPO release and kidney function
* EPO is released in the kidney in response to hypoxia (decreased renal blood flow), it stimulates RBC production in bone marrow
* dec urine output conserve PV
87
where is aldosterone secreted from
This is a steroid hormone secreted by outer zona glomerulosa of the adrenal cortex.
88
effect of decrease in plasma sodium and potassium concentration on aldosterone
* **A decrease in plasma concentration of Sodium activates the RAAS system, which causes aldosterone secretion.**
* **An increase in plasma concentration of Potassium stimulates the cells of the adrenal cortex directly to increase aldosterone secretion.**
* aldosterone acts to stimulate sodium reabsorption and potassium secretion
89
how much potassium is normally excreted in the urine
none
90
name 3 things which cause renin release
* reduced pressure in the afferent arteriole is sensed by the granular cells
* decreased NaCl in the distal tubule is sensed by the macula densa which stimulates the granular cells to release renin
* Increased sympathetic activity as a result of reduced arterial blood pressure
* Granular cells are directly innervated by the sympathetic nervous system and cause renin release
91
how does aldosterone increase Na reabsorption
* Aldosterone increases Sodium reabsorption in the distal and collecting tubule by increasing expression of NaK pump at the basolateral membrane, and apical Sodium channels.
92
does AGT II constrict the afferent or efferent arteriole more
efferent
93
where is ANP found and what generally does it do
* Synthesised, stored and released by atrial myocytes
* It is released when these cells are mechanically stretched due to an increase in circulating plasma volume
* Therefore, elevated levels are found during hypervolaemic states.
94
where is BNP produced and what is it a marker of
* ventricles - and brain
* secreted by ventricles in response to stretch
* diagnostic marker of heart failure
95
NP effect on veins and arteries
* dilate veins, decrease central venous pressure, which reduce CO by decreasing ventricular preload
* Dilate arteries which decreases systemic vascular resistance and systemic arterial pressure
* Does this by increasing vascular smooth muscle cGMP, and decreasing sympathetic vascular tone
96
NP effect on the kidneys
* Afferent arteriole vasodilation
* Increasing GFR which produces natriuresis and diuresis
* These renal effects are potassium sparing
* Decrease renin release, thereby decreasing circulating levels of AGT II and aldosterone. This leads to further natriuresis and diuresis
* ***= Counter regulatory system for RAAS***
97
water diuresis vs osmotic diuresis
In water diuresis, there is an increase urine flow but not an increased solute excretion.
In osmotic diuresis, the increased urine flow is as a result of primary increase in salt excretion. E.g. failure of normal Sodium reabsorption causes both increased sodium and water excretion.
*Any loss of solute in the urine must be accompanied by water loss (osmotic diuresis), but the reverse is not true (water diuresis is not necessarily accompanied by equivalent solute loss).*
98
filtration fraction
The fraction of plasma flowing through the glomeruli that is filtered into the tubules.
99
compare the pH of venous and arterial blood
venous blood is more acidic as it contains more CO2
100
dissociation of stong and weak acids in solution
strong acids dissociate completely, weak acids partly dissociate
101
proton donors and acceptors
Acids are proton donors, and bases are proton acceptors
102
Henderson-Hasselbalch equation
103
pH equation
pH = -log [H+]
104
pKa
-log [Ka]
105
what 3 things does H secretion by the tubule do
1. drive bicarbonate reabsorption
2. form acid phosphate
3. form ammonium ion
106
H secretion and bicarbonate reabsorption
* Bicarbonate is reabsorbed in the proximal tubule through the action of CA, unorthodox reabsorption at the apical membrane as the same bicarbonate ion that is absorbed does not cross the epithelium - *principal buffer*
* An increase in H ion secretion causes an increase in bicarbonate ion reabsorption
* An increase in CO2 has the same effect
107
H ion secretion forming acid phosphate
* The kidneys can regenerate buffer stores by generating new HCO3- if they are depleted by an acid load:
* When bicarbonate concentration in the tubular fluid is low, secreted H+ ions combine with **phosphate** (buffer). Acid is excreted with phosphate, and there is a net gain of 2 bicarbonate ions – **‘new bicarbonate.’**
108
measurement of H ions with as acid phosphate
* The amount of H ions secreted as H2PO4- can be measured as titratable acid – the amount of strong base (e.g. NaOH) that must be added to titrate the urine back to pH 7.4 is measured. This titration simply reverses the addition of H ions that has occurred as fluid flows along the tubule.
109
what is the maximum titratable acid that can be excreted
* The maximum amount of titratable acid that can be excreted is around 40mmol/day. If this much titratable acid is added, 40mmol/day of ‘new’ bicarbonate is simultaneously gained by the circulation
110
H secretion forming ammonium ion
* In severe acidosis, when the compensatory mechanisms are overloaded, **glutamine** from the liver is used as a tubular buffer. It diffuses as a gas into the tubular fluid. Acid is excreted as NH4+ and 2 new bicarbonate ions are generated per molecule
* can again be measured by titrable acid
111
