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Physiology Flashcards

1
Q

What is osmolarity?

A

Concentrated solution of osmotically active particles present in a solution

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2
Q

What are the units used for osmolarity?

A

osmol/l or mosmol/l

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3
Q

What needs to be known to calculate osmolarity?

A

Molar concentration of the solution and the number of osmotically active particles present
e.g.
150mM NaCl (150mmol/l)
No. of osmotically active particles = 2 (Na + Cl-)
Osmolarity = 2x150 = 300 mosmol/l

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4
Q

What is the difference between osmolality and osmolarity?

A

Osmolality has units of osmol/kg water
Osmolarity has units of osmol/l
For weak salt solutions (incl. body fluids) these 2 terms are interchangable

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5
Q

What is the osmolarity of body fluids?

A

300 mosmol/l

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6
Q

What is tonicity?

A

Effect a solution has on cell volume

Can be hypo, hyper and iso tonic

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7
Q

What is an isotonic solution?

A

No change in cell volume (no net movement of water)

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8
Q

What is a hypotonic solution?

A

More water; dilute salt solution

Increase in cell volume due to movement of water via osmosis from the ECF to the ICF

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9
Q

What is a hypertonic solution?

A

Less water; concentrated salt solution

Decrease in cell volume, cell losing fluid via osmosis from the ICF to the ECF

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10
Q

What, aside from the salt concentrations, has an impact on osmolarity?

A

Ability of a solute to cross the cell membrane

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11
Q

What percentage of the body weight is due to total body water in males and females?

A

Males - 60%

Females - 50% (due to more fat present)

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12
Q

What are the 2 compartments to total body water?

A

ICF (67% of TBW)

ECF (33% of TBW)

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13
Q

What is included in the extracellular fluid?

A

Plasma
Interstitial fluid
Lymph and transcellular fluid (negligible)

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14
Q

How can body fluid compartments be measured?

A

Tracers to obtain the distribution volume of a tracer

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15
Q

What are useful tracers?

A

TBW: 3H20
ECF: Inulin
Plasma: labelled albumin

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16
Q

How is the volume of distribution measured?

A

V (litres) = dose (D) / sample concentration (C)

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17
Q

How much fluid intake is there of a given day?

A

2500 ml

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18
Q

How much fluid is lost per day and where from?

A

Insensible: skin (350), lungs (350)
Sensible loss: sweat (100), faeces (200), urine (1500)
TOTAL: 2500

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19
Q

How is water imbalance manifested?

A

Body fluid osmolarity

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20
Q

What is the ionic composition of the ICF?

A

Sodium: 10
Potassium: 140
Chloride: 7
HCO3-: 10

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21
Q

What is the ionic composition of the ECF?

A

Sodium: 140
Potassium: 4.5
Chloride: 115
HCO3-: 28

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22
Q

What is fluid shift?

A

Movement of water between the ICF and ECF in response to an osmotic gradient

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23
Q

What would happen if the osmotic concentration of the ECF increases?

A

ICF will lose water to ECF to maintain fluid balance

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24
Q

What would happen if the osmotic concentration of the ECF decreases?

A

ICF will gain water from the ECF to maintain the fluid balance

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25
Q

What will happen if there is a gain or loss of NaCl?

A

Change in fluid osmolarity - Na+ excluded from ICF, causing osmotic water movements

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26
Q

What will happen if there is a gain or loss of isotonic fluid (0.9% NaCl)?

A

No change in fluid osmolarity

Change in ECF volume only

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27
Q

What organ alters the composition and volume of the ECF?

A

Kidneys

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28
Q

Why is electrolyte balance important?

A

Total electrolyte concentrations can directly affect water balance (via changes in osmolarity)
The concentrations of individual electrolytes can affect cell function

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29
Q

Describe sodium balance?

A

> 90% of the osmotic concentration of the ECF results from the presence of sodium salts
The total amount in the ECF represents a balance between 2 factors (input and output)
Sodium is mainly present in ECF - major determinant of ECF volume - water follows salt
VITAL to regulate Na+

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30
Q

Describe potassium balance?

A

Minor fluctuations in plasma potassium can have detrimental consequences
Potassium plays a key role in establishing membrane potential
>9% of K+ is ICF, small leakages can lead to paralysis and cardiac arrhythmias
K+ plasma must be closely monitored and regulated

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31
Q

What are the functions of the kidney?

A 
Water and salt balance
Maintenance of plasma volume
Maintenance of plasma osmolarity
Acid-base balance
Excretion of metabolic waste products
Excretion of exogenous foreign compounds 
Secretion of renin 
Secretion of erythropoietin 
Conversion of vitamin D to active form (calcitrol)
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32
Q

What are the functional mechanisms of the nephron?

A

Filtration
Reabsorption
Secretion

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33
Q

Describe the blood supply to the nephron

A 
Renal artery
Afferent arteriole
Glomerulus at the bowman's capsule
Efferent arteriole 
Peritubular capillaries 
Venule
Renal vein
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34
Q

What are the 2 different types of nephron?

A

Juxtamedullary - has vasa recta instead of peritubular capillaries
Cortical - smaller loop of helne

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35
Q

What makes up the glomerular membrane?

A

Endothelial cells
Basement membrane
Podocyte foot processes

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36
Q

What do the granular cells within the juxtaglomerular apparatus produce?

A

Produce and secrete renin

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37
Q

What is the function of the macula densa cells?

A

Salt sensitive cells, monitor salt levels in the tubular fluid passing through the juxtaglomerular apparatus

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38
Q

How much of plasma that enters the glomerulus is initially filtered to the kidney tubule?

A

20%

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39
Q

How is the rate of excretion calculated?

A

[X[ urine X Vu (Vu is urine production rate)

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40
Q

How is the rate of filtration calculated?

A

[x]plasma x GFR

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41
Q

What is the GFR of a normal, healthy kidney?

A

125 ml/min

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42
Q

How is the rate of reabsorption of a substance calculated?

A

Rate of filtration - rate of excretion

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43
Q

How is the rate of secretion calculated?

A

Rate of excretion - rate of filtration

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44
Q

How is GFR calculated?

A

Kf x net filtration pressure (Kf = filtration coefficient of glomerular membrane)

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45
Q

Why is the basement membrane of the glomerulus negatively charged?

A

To repel the negatively charged plasma proteins, they will therefore stay in the capillary and will not filter through

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46
Q

What are the forces that comprise net filtration pressure?

A

Glomerular capillary blood pressure
Bowman’s capsule hydrostatic (fluid) pressure
Capillary oncotic pressure
Bowman’s capsule oncotic pressure

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47
Q

What force does glomerular capillary blood pressure exert?

A

55 mmHg into the bowman’s capsule

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48
Q

What force does bowman’s capsule hydrostatic pressure exert?

A

15 mmHg into the capillary

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49
Q

What force does the capillary oncotic pressure exert?

A

30 mmHg into the capillary

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50
Q

What force does bowman’s capsule oncotic pressure exert?

A

0 mmHg into the bowman/s capsule

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51
Q

What are starling forces?

A

Balance of hydrostatic pressure and osmotic forces

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52
Q

What is the net filtration rate of a normal kidney?

A

10 mmHg, pushes fluid and small molecules to form the initial tubular fluid

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53
Q

What force has the largest impact on the net filtration rate and subsequent GFR?

A

Glomerular capillary BP

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54
Q

How does the glomerular capillary BP remain constant along the length of the capillary?

A

Due to the larger diameter of the afferent arteriole compared to the efferent arteriole

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55
Q

What is oncotic pressure?

A

Plasma proteins that will drug fluid along with it

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56
Q

What is the GFR?

A

The rate at which protein free plasma is filtered from the glomeruli into the bowman’s capsule per unit time

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57
Q

What is the extrinsic regulation of the GFR?

A

Sympathetic control via baroreceptor reflex

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58
Q

What is the intric regulation of the GFR?

A

Myogenic mechanism

Tubuloglomerular feedback mechanism

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59
Q

Describe the direct effect of arterial BP on GFR

A

Increased arterial BP increases blood flow into the glomerulus
Increased glomerular capillary BP
Increased net filtration pressure
Increased net filtration pressure

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60
Q

How will vasoconstriction and vasodilation affect GFR?

A

Vasoconstriction will reduce GFR

Vasodilation will increased GFR`

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61
Q

How is renal blood flow and GFR protected from changes in MABP?

A

Intrinsic (autoregulation) factors

Helps to prevent unwanted shifts in salt

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62
Q

What is the myogenic autoregulation?

A

If vascular smooth muscle is stretched (i.e. arterial pressure is increased), it contracts thus constricting the arteriole

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63
Q

What is the tubuloglomerular feedback autoregulation?

A

Involves the juxtaglomerular apparatus via macula densa cells whereby if GFR rises, and subsequently there is a rise in NaCl flowing through the tubule, there will be a constriction of the afferent arterioles

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64
Q

Describe what occurs to GFR in the case of a kidney stone

A

Increased bowman’s capsule fluid pressure, leading to a decreased GFR

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65
Q

Describe what occurs to GFR in the case of diarrhoea?

A

Increased capillary oncotic pressure due to a loss of water but not proteins, leading to a decreased GFR

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66
Q

Describe what occurs to GFR in the case of severe burns

A

Decreased capillary oncotic pressure due to a loss of plasma proteins, resulting in an increased GFR

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67
Q

What is plasma clearance

A

A measure of how effectively the kidneys can clean the blood of a substance
Equals the volume of plasma completely cleared of a particular substance per minute

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68
Q

How is clearance calculated?

A

[X] urine x V urine / [X] plasma

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69
Q

What unit is used in the clearance of a substance?

A

ml/min

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70
Q

Describe the properties of inulin

A 
Freely filtered at the glomerulus
Neither absorbed nor secreted
Not metabolised by the kidney
Not toxic
Easily measured in urine and blood
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71
Q

What does inulin clearance tell you?

A

GFR

72
Q

What is an alternative to inulin?

A

Creatinine

73
Q

What is a substance that has a clearance of 0?

A

Glucose - it is completely reabsorbed by the peritubular capillaries
Therefore if there is any glucose in the urine, it is abnormal

74
Q

What is a substance that is partly filtered by the kidneys and not secreted?

A

Urea

Clearance < GFR

75
Q

What is a substance that is filtered and secreted but NOT reabsorbed?

A

H+
All of the filtered plasma is cleared of H+
Clearance > GFR

76
Q

What does para-amino hippuric acid give an indication of?

A

Renal plasma flow - all PAH in plasma that escapes filtration is secreted from the peritubular capillaries

77
Q

What is the clearance value of inulin and creatinine?

A

125 ml/min

78
Q

What is the clearance value of PAH?

A

650 ml/min (value of renal plasma flow)

79
Q

How is filtration fraction calculated?

A

GFR/ renal plasma flow

80
Q

What is filtration fraction a measure of?

A

Fraction of plasma flowing through the glomeruli that is filtered into the tubules

81
Q

How is renal blood flow calculated?

A

RPF x 1/1-haematocrit

82
Q

Describe what the kidneys reabsorb?

A 
99% of fluid
99% salt
100% glucose 
100% amino acids
50% urea
0% creatinine
83
Q

What cannot get through the glomerular filtrate?

A

RBC

Large plasma proteins

84
Q

How much of filter fluid is reabsorbed in the proximal tubule?

A

80 ml/min

85
Q

What is the flow of filter fluid in the loop of henle?

A

45 ml/min

86
Q

Does the osmolarity of tubular fluid change as you move through the proximal tubule?

A

It does not - enters at 300 and leaves at 300

87
Q

What is reabsorbed in the PT?

A 
Glucose
Amino acids
Phosphate
Sulphate
Lactace
88
Q

What is secreted into the PT?

A 
H+ 
Hippurates
Neurotransmitters: ACh, noradrenaline, adrenaline 
Bile pigments
Uric acid
Drugs: atropine, morphine, penicillin
Toxins
89
Q

Describe the route of a substance that is reabsorbed transcellular?

A

Apical membrane
Cytoplasm
Lateral space (interstitial fluid)
Peritubular capillary

90
Q

What is paracellular transport?

A

In-between adjacent epithelial cells

91
Q

What is primary active transport?

A

Energy is directly required to operate the carrier and move the substrate against its concentration gradient

92
Q

What is an example of primary active transport?

A

Na+/K+ ATPase - moves 3 sodium out for 2 potassium in for every ATP that is hydrolysed

93
Q

What is secondary active transport?

A

The carrier molecule is transported coupled to the concentration gradient of an ion (usually Na+)

94
Q

What is facilitated diffusion?

A

Passive carrier-mediated transport of a substance down its concentration gradient

95
Q

What is a symporter?

A

Moving ions/substances in the same direction

96
Q

What is an antiporter?

A

Substance/ion moves in the opposite direction of sodium

97
Q

Where is the sodium potassium pump found for all epithelial cells?

A

On the basolateral membrane

98
Q

What does the sodium potassium pump help to maintain?

A

The low concentration of sodium within the cell, allowing for an ion gradient to be formed allowing for the transport of other ions/substances into the cell

99
Q

What will follow sodium?

A

Chloride ions - via paracellular route

100
Q

Is the PT tight junctions tight or leaky?

A

Leaky - allows for paracellular transport of water and chloride ions

101
Q

In the PT, what transport membranes are present?

A

Na+ glucose symporter
Na+ amino acid symporter
Na+ H+ antiporter

102
Q

Why is there no change in osmolarity as you move through the proximal tubule?

A

Salt and water are reabsorbed in equal concentrations

103
Q

How will salt and water get from the lateral space (interstitial fluid) to the peritubular capillary?

A

Via oncotic drag of the peritubular plasma

104
Q

How much of glucose is reabsorbed in the proximal tubule?

A

100%

105
Q

How will glucose get from the tubular filtrate to the lateral space?

A

Na+/glucose symporter into the tubular cell

Facilitated diffusion at the basolateral membrane into the interstitial fluid

106
Q

Will water follow glucose?

A

Yes

107
Q

What is the renal threshold for glucose?

A

10-12 mmol/l

More than this and you will excrete glucose in the urine

108
Q

What drives sodium reabsorption?

A

The basolateral Na+/K+ ATPase pump

109
Q

What is the function of the loop of henle?

A

Generates a cortico-medullary solute concentration gradient allowing the formation of hypertonic urine

110
Q

Describe fluid flow in the loop of henle

A

Opposing flow in the 2 limbs is termed countercurrent flow
The entire loop functions as a countercurrent multiplier
Together, the loop and vasa recta establish a hyper-osmotic medullary interstitial fluid

111
Q

What is reabsorbed in the ascending limb of the loop of henle?

A

NaCl

IMPERMEABLE TO WATER

112
Q

Describe the difference between the thick and thin ascending limbs of the loop of henle?

A

Thick AL achieves NaCl reabsorption via active transport

Thin AL achieves NaCl reabsorption via passive transport

113
Q

What is reabsorbed in the descending limb of the loop of henle?

A

HIGHLY permeable to water

Does NOT reabsorb NaCl

114
Q

What transporter is present in the thick ascending limb of the loop of henle?

A

Triple co-transporter: 1 sodium, 1 potassium, 2 chloride

115
Q

What happens to the potassium reabsorbed in the loop of henle?

A

It is recycled back into the tubular fluid to allow the absorption of NaCl

116
Q

What is the mechanism of action of loop diuretics?

A

Bind reversibly to the co transporter preventing the reabsorption of NaCl, decreasing interstitial hypertonicity and therefore water reabsorption
Increase the urinary K+ excretion by enhancing distal tubular K+ secretion and reducing K+ reabsorption in the loop of Henle

117
Q

Describe the changes in osmolarity as you move around the loop of henle

A

Solute removed from lumen of ascending limb via triple co-transporter but water cannot follow
Tubular fluid is diluted and osmolality of interstitial fluid is raised (increase in NaCl)
Interstitial solute cannot enter the descending limb
Water leaves descending limb via osmosis due to gradient set up
Fluid in descending limb is concentrated

118
Q

What type of fluid will the loop of henle produce?

A

Osmolarity of 100 mmosmol/l
Hypotonic solution: More water; dilute salt solution
Increase in cell volume due to movement of water via osmosis from the ECF to the ICF

119
Q

What is the difference in interstitial fluid osmolarity as you move from the cortex to the medulla?

A

Coretx: 300
Medulla: 1,200

120
Q

What effect does urea have on medullary osmolality?

A

Contributes around half of the osmolality as it adds solute to the interstitium
Collecting duct will reabsorb 50% of urea (ADH promotes)

121
Q

What is the purpose of countercurrent multiplication?

A

Concentrate medullary interstitial fluid to enable the kidney to produce urine of different volume and concentration according to the amounts of circulating ADH

122
Q

What is the osmolarity fo the interstitial fluid of the renal cortex?

A

300 mosomol/l

123
Q

What is the osmolarity of the interstitial fluid surrounding the collecting ducts?

A

300-1200 mosmol/l

124
Q

What is the primary action of ADH?

A

Increased water reabsorption - reduced urine production

125
Q

What is the primary action of aldosterone?

A

Increased sodium reabsorption

Increased hydrogen and potassium secretion

126
Q

What is the primary action of atrial natriuretic hormone?

A

Decreased sodium reabsorption

127
Q

What is the primary action of PTH?

A

Increased calcium reabsorption

Decreased phosphate reabsorption

128
Q

What is the permeability of the distal tubule?

A

Low permeability to water and urea - permeability is influences by the levels of ADH

129
Q

What is the action of the early distal tubule?

A

Na+/K+/2Cl- transport (NaCl transport)

130
Q

What is the action of the late distal tubule?

A

Ca2+ reabsorption
H+ secretion
Na+ reabsorption
K+ reabsorption

131
Q

What is the action of the late collecting duct?

A

Low ion permeability

Permeability to water (and urea) influenced by ADH

132
Q

Where is ADH synthesised and secreted?

A

Supraoptic and paraventricular nuclei in the hypothalamus
Transported down nerves to terminals where it is stored in granules in the posterior pituitary
Released into blood when action potentials down the nerves lead to Ca2+ dependent exocytosis

133
Q

What effect does ADH have on the collecting ducts?

A

Increases the permeability of the luminal membrane to water by inserting new aquaporins via increased cAMP within the cell

134
Q

Describe the actions of a high ADH

A

High water permeability
Hypertonic urine
Presence of ADH moves water from the collecting duct lumen into the medullary interstitial fluid vi osmotic gradient forming a hypertonic urine

135
Q

Describe low plasma ADH

A 
Low water permeability
Hypotonic urine (<50 mosmol)
136
Q

What are the symptoms of diabetes insipidus?

A

Large volumes of dilute urine (20 litres a day)

Constant thirst

137
Q

What can cause cranial DI?

A

Trauma to the hypothalamus or posterior pituitary

DIDMOAD (DI + DM + optic atrophy + deafness)

138
Q

What can cause nephrogenic DI?

A

Inherited
Lithium
CKD

139
Q

What is the most important stimulator for ADH release?

A

Hypothalamic osmoreceptors

Also via activation of left atrial stretch receptors

140
Q

What is the action of nicotine and ADH?

A

Stimulates ADH release

141
Q

What is the action of alcohol and ecstasy on ADH?

A

Inhibits release - high volumes of dilute urine

142
Q

Describe tubular flows as you move through the nephron?

A

GFR/ proximal tubule = 125 ml/min
Loop of henle: 45ml/min to 25 ml/min
Distal tubule: 8ml… with ADH: 0.2ml/min
Without ADH: 20 ml/min

143
Q

What is aldosterone?

A

Steroid hormone secreted by the adrenal cortex

144
Q

What is the action of aldosterone?

A

Stimulates sodium reabsorption and potassium secretion

145
Q

How is aldosterone initiated to reabsorb sodium and secrete potassium?

A

Increase in potassium acts directly on the zone glomerulosa to secrete aldosterone
Decrease in sodium will be detected by macula densa cells, activate RAAs system leading to the release of aldosterone

146
Q

How does aldosterone increase BP?

A

Water follows salt; it will follow sodium, increasing circulating volume

147
Q

What happens with a lack of aldosterone?

A

Salt wasting
Hypotension
ADDISON’S SYNDROME

148
Q

What happens with too much aldosterone?

A

Hypernatraemia
Hypokalaemia
Hypertension
CONN’S SYNDROME

149
Q

Where is the majority of K+ reabsorbed?

A

Early regions of the nephron - mainly in the proximal tubule

150
Q

Describe the RAAS system

A

Decreased NaCl/ ECF/ BP
Liver produces angiotensinogen which is converted to angiotensin 1 by renin
This is converted to angiotensin 2 via ACE in the lungs which acts on the adrenal cortex to release aldosterone

151
Q

What are the actions of angiotensin 2?

A

Increased ADH
Increased thirst
Increased arteriolar constriction

152
Q

What cells release renin?

A

Granular cells of the juxtaglomerular apparatus

153
Q

How is renin release from the granular cells controlled by reduced pressure in afferent arteriole?

A

More renin released
More Na+ reabsorbed
Increased blood vol
Increased BP

154
Q

How is renin release from the granular cells controlled by the macula densa cells?

A

If NaCl reduced, more renin released, more Na+ reabsorbed

155
Q

How is renin release from the granular cells controlled by symp activity?

A

Granular cells are directly innervated by sympathetic nervous system, causing renin release

156
Q

Where will aldosterone act?

A

Distal and collecting tubules - will cause effects via changes in gene expression and protein synthesis causing an increase in sodium channels at the apical membrane and increased Na+/K+ ATPase pumps at the basolateral membrane

157
Q

What is the pathophysiology of the RAAS and heart failure?

A 
Failing heart
Decreased CO and BP 
Stimulation of RAAS 
Increased salt and water retention 
Oedema
158
Q

When is ANP released?

A

Atrial cells are physically stretched due to an increase in the circulating plasma volume

159
Q

What are the actions of ANP?

A 
Decreases: 
Na+ reabsorption 
RAAS
Smooth muscle of afferent arterioles 
Sympathetic nervous system
160
Q

What is the is purpose of ANP relaxing the smooth muscle of afferent arterioles?

A

Afferent arteriole vasodilation
Increased GFR
Increased sodium and water

161
Q

What is the purpose of ANP decreasing the sympathetic nervous system output?

A

Decreased CO
Decreased total peripheral resistance
Decreased arterial BP

162
Q

Describe urination

A 
Bladder fills
Stretch receptors
Parasympathetics
Bladder contracts 
Internal urethral sphincter opens 
Stretch receptors can also tell the cerebral cortex to stimulate motor neurones closing the external urethral sphincter
163
Q

Describe the relationship between osmolality and ADH?

A

Increased osmolality - dehydration

Increased ADH

164
Q

What occurs in water diuresis?

A

Increased urine flow but not an increased solute excretion

165
Q

What occurs in osmotic diuresis?

A

Increased urine flow is as a result of a primary increase in salt excretion - a failure of normal Na+ reabsorption causes both increased sodium and increased water excretion

166
Q

What can acidosis lead to?

A

Depression of the CNS

167
Q

What can alkalosis lead to?

A

Overexcitability of the peripheral NS and CNS

168
Q

What effect does hydrogen have on potassium?

A

Increased hydrogen secretion by cells in the tubul, will lead to potassium retention

169
Q

How is H+ added to the body fluids?

A

Carbonic acid formation
Inorganic acids produced during breakdown of nutrients
Organic acids resulting from metabolism

170
Q

Describe the difference between strong and weak acids?

A

Strong acids dissociate completely in a solution

Weak acids dissociate partially in a solution

171
Q

What is the most important physiological buffer system?

A

Carbonic anhydrase
Carbonic acid
Base-bicarbonate

172
Q

What controls bicarbonate and carbon dioxide?

A

HCO3- kidneys

pCO2 - lungs

173
Q

How do the kidneys control bicarbonate?

A

Conserving filtrated bicarb

Generate new bicarb to regenerate buffer stores depleted by an acid load

174
Q

What will hydrogen ions bind to when bicarb tubular concentrations are low?

A

Phosphate to form phosphoric acid - this is titratable acid

175
Q

What does hydrogen secretion in the tubule do?

A

Drives reabsorption of bicarb and the generation of new bicarb
Forms acid phosphate
Forms ammonium ions

Renal (22 decks)

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