physiology Flashcards
1
Q
Total body water (TBW) - proportion
A
60% of body mass
2
Q
Non water mass (NWM) - proportion
A
40% of body mass
3
Q
total body water mass and non water mass if Body mass is 70kg
A
- total body water –> 60% of body mass = 42kg = 42L
- non water mass –> 40% of body mass = 28kg
4
Q
Total body water (TBW) is divided to … (and proprotions)
A
- extracellular fluid (ECF) –> 1/3
2. intracellular fluid (ICF) –> 2/3
5
Q
extracellular fluid (ECF) in a body mass 70kg
A
1/3 of 60% body mass –> 20% of body mass –> 14kg
–> 28L
6
Q
intracellular fluid (ICF) in a body mass 70kg
A
2/3 of 60% body mass –> 40% of body mass –> 28kg
–> 28L
7
Q
extracellular fluid (ECF) vs intracellular fluid (ICF) according to proportion in body mass
A
extracellular fluid (ECF) --> 20% intracellular fluid (ICF) --> 40%
8
Q
extracellular fluid (ECF) is divided to (proportions and L in body mass 70 kg)
A
- interstitial fluid –> 75% ECF –> 10.5 kg –> 10.5 L
2. plasma –> 25% ECF –> 3.5kg –> 3.5 L
9
Q
RBC volume
A
2.8 L (part of intracellular fluid)
10
Q
blood conistis of (and volumes)
A
RBCs (2.8.L) and plasma (3.5L) –> 6.2 L
11
Q
Normal HCT (calculation and alternative calculation)
A
RBC volume/blood volume = 2.8/6.2 = 45%
altenatively –> HCT(%) = 3X(Hb) in g/dL
12
Q
Plasma volume can be measured by
A
radiolabeling albumin
or Evans blue (it binds albumin)
13
Q
Extracellular volume can be measured by
A
inulin or manitol, or sulfate
14
Q
osmolarity is the
A
measure of solute concentration, defined as the number of osmoles (Osm) of solute per litre (L) of solution
15
Q
osmolarity - normal range
A
285-295 mOsm/kg H2O
16
Q
Glomerular filtration barrier is responsible for
A
filtration of plasma according to size and net charge
17
Q
Glomerular filtration barrier is composed of (and role of every component)
A
- fenestated capillary endothelium –> SIZE BARIER
- fused basement membrane with heparan sulfate –> NEGATIVE CHARGE AND SIZE BARRIER
- epithelial layers consisting of podocyte foot processes –> NEGATIVE CHARGE BARRIER
18
Q
Glomerular filtration barrier - components for size barrier and components for charge barrier
A
size: 1. fenestated capillary endothelium 2. fused basement membrane
charge: 1. fused basement membrane 2. epithelial layers consisting of podocyte foot processes
19
Q
Charge barrier is lost in ….(and clinical presentation)
A
nephrotic syndrome –> 1. albuminuria 2. hypoproteinemia
3. generalized edema 4. hyperlipidemia
20
Q
renal clearance - definition
A
volume of plasma from which the substance is completely cleared per unit (from renal)
21
Q
renal clearance - calculation
A
Cx=Ux.V/Px CX=Clearance of x (ml/min) Ux=urine concentration of x (mg/ml) Px=plasma concentration of X (mg/ml) V=urine flow rate (ml/min)
22
Q
if renal clearance equals/smaller/bigger than GFR
A
Cx smaller: if smaller net tubular reabsorption of X
Cx bigger: net tubular secretion of X
Cx=GFR: no net secretion or reabsorption
23
Q
Inulin clearance can be used to … (why)
A
caclulate GFR because it is freely filtered and is neither reabsorder nor secreted
24
Q
Glomerular filtration rate (GFR) estimates
A
how much blood passes through the glomeruli each minute.
25
GFR calculation
GFR = inulin clearance = (Urine concentration of inulin x urine flow rate) / plasma concentration of inulin = Starling equation
26
Normal GFR =
100ml/min
27
Starling equation
```
GFR= Kf ((Pgc - Pbs) - (πgc-πbs))
gc: glomerular capillary
bs: Bowman space
Kf: filtration constant
πbs = 0
```
28
creatinine clearance - clinical relevance
it is an approximate measure of GFR --> slightly overestimates GFR because creatinine is moderaterly secreted by renal tubules
29
chronic kidney disease - GFR measure
incremental reductions in GFR define the stages of chronic kidney disease
30
creatinine serum concentration
0.6-1.2mg/dL or 53-106μmol/L
31
Effective renal plasma flow (eRPF) is used to
calculate renal plasma flow (RPF) and hence estimate renal function.
32
Effective renal plasma flow (eRPF) can be estimating using ... (why)
para-aminohippurinc (PAH) clearance because filtration and secretion is nearly 100% excretion of all PAH that enter kidney
33
Effective renal plasma flow (eRPF) calculation
para-aminohippurinc (PAH) clearance = Upah x V/Ppah
34
renal blood flow (RBF) is the
volume of blood delivered to the kidneys per unit time
35
renal blood flow (RBF) - calculation
renal blood flow (RBF) = RPF/(1-Hct)
| 1-HcT=plasma
36
eRPF vs true renal plasma flow
eRPF underestimates true renal plasma flow slightly
37
renal filtration fraction - definition
is the ratio of the glomerular filtration rate (GFR) to the renal plasma flow (RPF)
38
Renal filtration fraction - caclulation and normal value
FF=GFR/RPF = 20% (normally)
39
Filtered load calculation
Filtered load (mg/min) = GFR(ml/min) x plasma concentration (mg/ml)
40
effect of NSAID on renal function
NSAIDs inhibit prostagladins (that preferentially dilated afferent arteriole and increase RPF and GFR, not the FF)
- -> constriction of afferent arteriole --> decrease of RPF and GFR, not the FF --> IN LOW RENAL BLOOD SATES
- -> ACUTE RENAL FAILUE
41
effect of ACE inhibitors on renal function
ACE inhibitors decrease angiotensin 2 (that preferentially constricts efferent arteriole and decrease RPF, increase GFR and increase FF) --> dilation of efferent arteriole --> increas RPF, decreased GFR, so decrease FF)
42
prostagladins vs angiotensin 2 on renal function
- prostagladins --> preferentially dilated afferet arteriole and increase RPF and GFR, not the FF
- angiotensin 2 --> inhibits preferentially constricts efferent arteriole and decrease RPF, increase GFR and increase FF
43
Afferent arteriole constriction - GFR, PRF, FF?
GFR: decreased
RPF: decreased
FF: -
44
efferent arterile constriction - GFR, PRF, FF?
GFR: increased
RPF: decreased
FF: increased
45
increased plasma protein concentration - GFR, PRF, FF?
GFR: decreased
RPF: -
FF: decreased
46
decreased plasma protein concentration - GFR, PRF, FF?
GFR: increased
RPF: -
FF: increased
47
constriction of ureter - GFR, PRF, FF?
GFR: decreased
RPF: -
FF: decreased
48
dehydration- GFR, PRF, FF?
GFR: decreased
RPF: decreased
FF: INCREASED
49
filtration fruction on dehydration?
increased
50
renal - filtration, reabsorption, secretion excretion???
aaaa
51
renal - Filtered load - calculation
GFR X plasma concentration
52
renal - Excretion rate - calculation
urine flow rate (ml/min) x urine concentration
53
renal - how to estimate secretion
Secretion = excreted - filtered
54
renal - how to estimate urinary excretion
urinary excretion = glomerular filtration - tubular reabsorption + Tubular secretion
55
FENa?
fractional excretion of sodium
56
fractional excretion of sodium (FENa) - definition?
it is the percentage of the sodium filtered by the kidney which is excreted in the urine
57
fractional excretion of sodium (FENa) - calculation
Na+ excreted/Na+ filaterd = (urine flow rate x urine concentration of Na+) / (GFR x plasma concentration of Na+) = (urine flow rate x urine concentration of Na+) / (Ucr x V/Pcr x plasma concentration of Na+) =
(Pcr x U Na) / (Ucr x P Na)
58
Glucose clearance - describe
Glucose at a normal plasma level is completely reabsorbed in proximal convoluted tubule by Na+/gluocse contrasport
59
glucose in serum in serum (normally)
fasting: 70 - 110 mg/dL (3.8-6.1 mmol/L)
| 2h postpradial: less than 120mg/dL, less than 6.6mmol/L
60
glucose in serum in cerebrospinal fluid (normally)
40-70 mg/dL
| 2.2-3.9 mmol/L
61
glucose in urine - concentrations (in adults)
In adults, at plasma glucose of 200 mg/dL --> glucosouria begins. At rate of 375 mg/min, all trasnportes are fully saturated
62
glucosouria is an important clinical clue to
diabetes mellitus
63
glucose clearance - splay?
is the region of substance clearance between threshold and Tm --> it is due to heterogeneity of nephrons
64
glucose clearance - pregnancy
normal pregnancy may decrease ability of proximal convoluted tubule to reabsorb glucose and aminoacids
--> glucosouria and aminoaciduria
65
mechanism that induce glucosouria and aminoaciduria in normal pregnancy
normal pregancy may decrease ability of proximal convoluted tubule to reabsorb glucose and aminoacids
66
nephron anatomy (and cortex vs medulla)
glomerulus (cortex) --> proximal convoluted tubule (cortex and medulla) --> descending limb loop of Henle (medulla) --> loop of henle (medulla) --> ascending limb of henle (medulla and cortex)--> distal convoluted tubule (cortex) --> collecting duct
67
Nephron physiology - early proximal convoluted tubule structure
it contains brush border
68
Nephron physiology - early proximal convoluted tubule - reabsorbs
all glucose and aminoacis
most HCO3-, Na+ (65-80%), CL-, PO4, k+, H2O, uric acid, lactate
ISOTONIC ABSORPTION
69
Nephron physiology - early proximal convoluted tubule -secretes
1. secretes H+ (Na-H+ exchange)
2. secretes NH3 (as a buffer for secreted H+)
3. base - (CL- - base - exchange)
70
Nephron physiology - early proximal convoluted tubule - reabsorbs Na+ is absorbed via
- cotrnasport with glucose, aminoacids, phosphate and lactate
- countertrasnport via Na-H+ (linked with HCO3)
71
Nephron physiology - early proximal convoluted tubule - hormones
1. PTH
| 2. ATII
72
Nephron physiology - early proximal convoluted tubule - PTH
It inhibits Na/PO4 cotransport --> increased PO4 excretion
73
Nephron physiology - early proximal convoluted tubule - AT II
stimulates Na/H+ exchange --> increased Na+, H2O and HCO3- reabsorption --> permit contraction alkalosis
74
Nephron physiology - early proximal convoluted tubule - basolateral membrane
- Na+/K+ pump
| - HCO3 channel
75
Nephron physiology - early proximal convoluted tubule - Carbonic anhydrase - action
- in the cell --> CO2 + H2O --> H + HCO3- --> H+ in the lumen and HCO3 in the blood
- in the lumen --> H + HCO3- --> CO2 + H2O --> in the cell
76
Nephron physiology - late proximal tubule - action
Na+ is reabsorbed with CL-
77
Nephron physiology - thin descending loop of Henle - function
passively reabsords H2O via medullary hypertonicity (impermeable to Na+) --> Concentrating segment -->
Makes urine hypertonic
78
Nephron physiology - thick ascending loop of Henle - function
1. reabsorb 1Na+, 1K+ and 2CL- --> K+ is goining either to the blood (basalateral membrane) or back to the lumen
- -> generates + lumen (K+ backleaking) --> induces paracellular reabsorption of Mg2+ and Ca2+ (to blood)
2. Impermeable to H2O --> urine less concentrated
3. CL- is going to the blood (down the electrochemical gradient)
79
Nephron physiology - thick ascending loop of Henle - H2O
Impermeable to H2O --> urine less concentrated
80
Nephron physiology - thick ascending loop of Henle - basolateral membrane
1. Na+/k+ pump
| 2. k+ and CL- channel to their electrochemincal gradient (to the blood)
81
proportion of Na+ reabsorption in proximal convoluted tubule and in thick ascending loop of Henle
- proximal convoluted tubule --> 65-80%
| - thick ascending loop of Henle --> 10-20%
82
Nephron physiology - early distal convoluted tubule - function
1. reabsorbs Na/CL- (cotransportation) and Ca2+
| 2. makes urine fully dilute (hypotonic)
83
Nephron physiology - early distal convoluted tubule - hormones (and action)
PTH --> increases Ca+/Na+ exchange on he basolateral membrane --> increases Ca2+ reabsorption
84
Nephron physiology - early distal convoluted tubule - basolateral membrane
- Na+/K+ pump
- cl channel
- Na+ /ca2+ exchanger
85
proportion of Na2+ reabsorption in proximal convoluted tubule, in thick ascending loop of Henle, and in early distal convoluted tubule
- proximal convoluted tubule --> 65-80%
- thick ascending loop of Henle --> 10-20%
- early distal convoluted tubule --> 5-10%
86
Nephron physiology - collecting tubule - function
reabsorbs Na+ in exchange for secreting K+ and H+:
1. k+ channel to lumen
2. Na+ channel into cell
3. H+ ATPase to lumen
4. H+/K+ pump (H+ to lumen, K+ into cell)
5. CL/HCO3 exhanger (CL into cells)
6. aquaporin (H20) channels)
87
Nephron physiology - collecting tubule - type of cells
1. principal cells
2. α-intercalated cells
3. β-intercalated cells
88
Nephron physiology - collecting tubule - hormones
1. Aldosterone
| 2. ADH
89
Nephron physiology - collecting tubule - aldosterone action
acts on mineralocorticoid receptor --> mRNA --> proteins synthesis:
1. in principal cells --> a. increases apical (to the lumen) K+ conductase b. increases Na/K pump (basolateral)
c. increases epithelial Na+ channel (ENaC) activity --> lumen negatiivty --> K+ secretion
2. in α-intercalated cells --> lumen negativity --> H+ ATPase activity --> increased H+ secretion --> HCO3-/CL- (Cl in the cell) exchanger activity (in β-intercalated cells)
90
Nephron physiology - collecting tubule - ADH action
acts at V2 receptor --> insertion of aquaporin (H20 channels) on apical side
91
Nephron physiology - collecting tubule - function (and which cells)
reabsorbs Na+ in exchange for secreting K+ and H+. It also absorb H20:
1. k+ channel to lumen (principal cells)
2. Na+ channel into cell (principlal cells)
3. H+ ATPase to lumen (α-intercalated cells)
4. H+/K+ pump (H+ to lumen, K+ into cell) ( α-intercalated cells)
5. CL/HCO3 exhanger (CL into cells) (β-intercalated cells)
6. aquaporin (H20 channels) (principal cells)
92
Nephron physiology - location of PTH action
1. early proximal convoluted tubule
| 2. early distal convoluted tubule
93
Nephron physiology - location of ATII action
early proximal convoluted tubule
94
Renal tubular defects - types
1. Fanconi syndrome
2. Bartter syndrome
3. Gitelman syndrome
4. Liddle syndrome
5. Syndrome of apparent minelocorticoid excess
95
Fanconi syndrome - pathophysiology
Generalized reabsorptive defect in early proximal convoluted tubule
96
Fanconi syndrome --> ...(result in)
increased amino acids, glucose, HCO3- and PO4- -- Metabolic acidosis (proximal renal tubular acidosis)
97
causes of Fanconi syndrome
1. hereditary defects (Wilson disease, tyrosinemia, glycogen storage disease, cystinosis)
2. iscemia
3. multiple myeloma
4. nephrotoxins/drugs (expired tetracyclines, ifosfamide, cisplatin, tenofovir, lead poisoning)
98
nephrotoxins/drugs that cause Fanconi syndrome
1. ifosfamide
2. cisplatin
3. tenofovir
4. lead poisoning
5. expired tetracyclines
99
Bartter syndrome - pathophysiology (and result in)
Reabsorptive defect in thick ascending loop oh Henle
| --> affects Na+/K+/2CL- cotransporter -->
100
Bartter syndrome --> .... (result in)
1. hypokalemia
2. metabolic alkalosis
3. hypercalciuria
101
Situation that mimics Bartter syndrome
chronic loop diuretic use
102
Loop diuretics - drugs
1 Furosemide
2. Buetanide
3. torsemide
4. Ethracrynic acid
103
Bartter syndrome - mode of inheritance
AR
104
Gitelman syndrome - pathophysiology
Reabsosptive defect in Distal convoluted tubule
105
Gitelman syndrome - Mode of inheritance
AR
106
situation that mimics Gitelman syndrome
lifelong thiazide diuretics
107
thiazide diuretics: drugs
1. Hydrochlorothiazine
2. Chlorothalidone
3. Metolazone
108
Gitelman syndrome --> .... (results in)
1. hypokalemia
2. hypomagnesia
3. metabolic alkalosis
4. hypocalciuria
109
Gitelman syndrome vs Barrter syndrome according to severity
Barrter is more severe
110
Liddle syndrome - pathophysiology
Gain of function mutation --> increased Na+ reabsorption in collecting tubules (high activity of epithelial channel)
111
situation that mimics Liddle syndrome
hyperaldosternism (but aldosterone is nearly undetectable)
112
Liddle syndrome - mode of inheritance
AD (gain function mutation)
113
Liddle syndrome --> ..... (result in)
1. hypertension
2. hypokalemia
3. metabolic alkalosis
4. low aldosterone
114
Liddle syndrome - treatment
amiloride
115
Syndrome of Apparent Mineralocorticoid excess - pathophysiology
hereditary deficiency of 11β-hydroxysteroid dehydrogenase which normally converts cortisol (can activate mineralocorticoid receptors) to cortizone (inactivate on mineralocorticoid receptors) in cell containing mineralocorticoid receptors --> increased mineralocorticoid activity
116
Syndrome of Apparent Mineralocorticoid excess - manifestations
1. hypertension
2. hypokalemia
3. metabolic alkalosis
4. low serum aldosterone levels
117
situation that mimics Apparent Mineralocorticoid excess
glycyrrhetinic acid (present in licorice) which blocks activity of 11β-hydroxysteroid dehydrogenase
118
licorice, is the root of
Glycyrrhiza glabra from which a sweet flavour can be extracted (wide variety of candies or sweets)
119
Apparent Mineralocorticoid excess - treatment
coirticosteroids --> decreases endogenous cortisol production --> decrease mineralocorticoid receptor activation
120
Renal tubular defects - types
1. Fanconi syndrome
2. Bartter syndrome
3. Gitelman syndrome
4. Liddle syndrome
5. Syndrome of apparent minelocorticoid excess
121
Relative concentrations along proximal convoluted tubules - (Tubular fluid)/plasma (smaller, bigger, equals 1)
TF/P bigger than 1 --> when solute is reabsorded less quickly than water
TF/P smaller than 1 --> when solute is reabsorded more quickly than water
TF/P=1 --> when solute and water are reabsorbed at the same rate
122
Relative concentrations along proximal convoluted tubules - substance with TF/P=1
Na+
123
Relative concentrations along proximal convoluted tubules - substance with TF/P smaller than 1 (explain) (in order)
from more negative to 0
1. Glucose
2. aminoacids
3. HCO3
solutes is reabsorded more quickly than water
--> concentration in plasma is bigger than tubule
124
Relative concentrations along proximal convoluted tubules - substance with TF/P bigger than 1 (explain) (in order)
from more positive to 0
1. PAH 2. Creatine 3. inulin 4. urea
5. CL- 6. k+ water is reabsorbed more quicly than solutes (or solutes secretion --> concentration in tubule is bigger than plasma
125
Relative concentrations along proximal convoluted tubules - substance with TF/P=1
Na+
126
Relative concentrations along proximal convoluted tubules - inulin (explain)
TF/P is bigger than 1 --> tubular inulin increases in concentration (BUT NOT AMOUNT) along the PCT as a result of water reabsorption
127
Relative concentrations along proximal convoluted tubules - CL- (explain)
TF/P is bigger than 1 --> CL- reabsorption occuts at a slower rate than Na+ in early PCT and then matches at the rate of Na+ reabsorption more distally -> thus, its relative concentration increases before it platues
128
Total body water can be measured by
1. Tritiated water
2. D2O
3. Antipyrene
129
proportion of Na2+ reabsorption in proximal convoluted tubule, in thick ascending loop of Henle, in early distal convoluted tubule, collecting tubules
- proximal convoluted tubule --> 65-80%
- thick ascending loop of Henle --> 10-20%
- early distal convoluted tubule --> 5-10%
- collecting tubule --> 3-5%
