PHSL233 Term Flashcards
1
Q
Which processes are required for establishing epithelial polarity?
a) Neighboring cells interacting with each other through adherens junctions
b) Connections between epithelial cells and their basement membrane
c) Nectin proteins from neighboring cells connecting with each other
d) All of the above
A
d) All of the above
2
Q
Which is the correct order for entry of secretory pathway proteins into the endoplasmic reticulum (ER)?
a) signal peptide cleaved - protein enters via translocon - binding of ribosome to ER
b) protein enters via translocon - signal peptide cleaved - SRP (signal recognition particle) binds signal sequence
c) SRP binds signal sequence - ribosome docks on ER - protein enters via translocon
A
c) SRP binds signal sequence - ribosome docks on ER - protein enters via translocon
3
Q
Choose the CORRECT statement about polarity protein complexes:
a) aPKC phosphorylates Scrib polarity proteins to keep them basolateral
b) Both the Par and Crb complexes are basolateral
c) The Scrib complex is basolateral
d) A and C are correct
A
d) A and C are correct
4
Q
Which order is correct for trafficking of a protein in the secretory pathway?a) Endoplasmic reticulum (ER)-endosome-Goldi-cell surfaceb) endoplasmic reticulum (ER)-Golgi-cell surfacec) nucleus-lysosome-cell surface
A
b) endoplasmic reticulum (ER)-Golgi-cell surface
5
Q
Which is the CORRECT order for entry of secretory pathway proteins into the ER?a) signal peptide cleaved - protein enters via translocon - binding of ribosome to ERb) protein enters via translocon - signal peptide cleaved - SRP (signal recognition particle) binds signal sequencec) SRP binds signal sequence - ribosome docks on ER - protein enters via translocon
A
c) SRP binds signal sequence - ribosome docks on ER - protein enters via translocon
6
Q
“Which statement about protein topology is CORRECT?
a) ““stop-transfer”” sequences remain in the ER membrane as transmembrane domains
b) In the ER, the region of a transmembrane protein in the cytosol will end up outside the cell
c) The N-terminal end of a protein always enters the lumen of the ER.”
A
“a) ““stop-transfer”” sequences remain in the ER membrane as transmembrane domains”
7
Q
Which post-translational modification occurs in the ER?a) transcription; N-linked glycosylation; degradation
b) assembly of protein complexes; disulphide bridges; O-linked glycosylation
c) GIP anchors added; N-linked glycosylation; chaperone-mediated folding
A
c) GIP anchors added; N-linked glycosylation; chaperone-mediated folding
8
Q
Endocytosis of transmembrane proteins occurs through interaction with the AP2 compex BECAUSE the transmembrane proteins contain endocytosis motifs such as YXXφ.
a) Both statements are true and causal
b) Both statements are true but not causal
c) First statement true, second false
d) First statement false, second true
e) Both statements false.
A
a) Both statements are true and causal
9
Q
Choose the CORRECT statement about protein sorting and targeting in epithelia
a) The exocyst is the site for delivery of proteins to the basolateral membrane
b) Experimental evidence shows that the trans-Golgi network (TGN) can sort apical and basolateral proteins into separate vesicle populations
c) In the indirect sorting pathway, all proteins are first delivered to the same membrane domain.
d) All of the above are correct.
A
d) All of the above are correct.
10
Q
Lysosomes only degrade proteins BECAUSE monoubiquitin is used as a tag for degradation in the endocytosis pathway.
a) Both statement true and causal
b) Both statement true but not causal
c) First statement true, second false
d) First statement false, second true
e) Both statements false
A
d) First statement false, second true
11
Q
functions of the kidney
A
-regulation of water and ion balance, body pH-excretion of metabolic wastes-excretion of foreign chemicals-endocrine functions (calcitriol, erytropoietin, renin-gluconeogenesis
12
Q
Define polarity
A
A difference in structure, composition or function between the two poles of a cell, such as, apical/basolateral in an epithelial cell.In epithelial cells this also means location of a protein in a specific location in the cell membrane
13
Q
Which statement is CORRECT about Kidney?
a) The kidney filters about 200L of plasma /day
b) The kidneys do not produce hormones
c) The urinary system has 3 ureters
d) The kidneys excrete foreign chemicals
e) The kidneys receive 50% of the blood flow
A
d) The kidneys excrete foreign chemicals
14
Q
how much plasma do the kidneys filter each day?
A
~180L
15
Q
Why is polarity important in epithelia?
A
Depending on the exact transporters and channels present in each membranedomain this will dictate whether that epithelia primarily absorbs or secretessubstances
16
Q
how much of the total filtrate is reabsorbed?
A
99%
17
Q
How are epithelia ‘made’?
A
If single epithelial cells are placed on a substrate that resembles the basementmembrane, the cells attach to that substrate and start showing signs of somepolarity. If the cells are allowed to divide so that all cells are close to their neighbours, aswell as linking with the basement membrane, cell-cell contacts such as tightjunctions now develop, and the cytoskeleton starts forming under thebasolateral membrane. Ca2+ is needed for cell-cell contacts to form. Upon Ca2+ addition adherens junctions and then tight junctionsformed and the Na+K+ATPase now localised to the basolateral domain. However,full epithelial polarity is not observed until 36 hours after tight junctions areformed
18
Q
renal blood flow
A
-kidney supplied by renal artery-renal artery divides to form glomerular and peritubular capillaires, and vasa recta-renal veins tale blood away from kidneys
19
Q
What are the three protein polarity complexes?
A
Par, Crb and Scrib
20
Q
types of nephrons
A
-superficial (cortical)-juxtameduallary
21
Q
How is epithelial cell polarity established?
A
-Formation of adherens junction (AJ, nectin, E>cadherin) and interactions between cells and basement membrane-Small GTP proteins (cdc42) activated-Cdc42 activates aPKC, Par complex associates with apical domain-Crb complex associates with Par complex-aPKC phosphorylates proteins causing change in location e.g. scrib complex to BL region-TJ proteins start forming TJ apical to AJ-Full mutual exclusion of polarity complexes: Par/Crb complex in apical region; scrib in basolateral region-TJ fully formed, apical-basolateral polarity established
22
Q
3 types of processes of the nephron
A
-glomerular filtration-tubular secretion-tubular reabsorption
23
Q
What is the trafficking pathway that plasma membrane proteins follow?
A
CytosolEndoplasmic reticulumGolgiCell surface
24
Q
Which statement is INCORRECT about Nephron?
a) The nephron is the smallest functional unit of the kidney
b) The afferent arteriole branches to make the glomerulus
c) Each kidney contains more than 1 million nephrons
d) Reabsorption of material is from the blood to the lumen of the nephron
e) Juxtamedullary nephrons are located within the medulla of the kidney
A
d) Reabsorption of material is from the blood to the lumen of the nephron
25
How do proteins enter the endoplasmic reticulum
Proteins contain an address label called a signal sequence that guides a ribosome translating a cell membrane protein to theendoplasmic reticulum. The signal sequence is bound by the signal recognition particle and translation stops until the ribosome docks onto the endoplasmic reticulum. Translation starts again and the protein is threaded through a 'pipe' or protein translocation channel called the translocon into the lumen of the endoplasmic reticulum.
26
What is glomerular filtration?
-bulk flow of protein-free plasma into the bowman's space (forms filtrate)-the filtrate contains everything in plasma except RBC and protein
27
Which statement is FALSE about Renal Clearance and GFR?
a) The typical GFR for a healthy person is 125ml/min
b) RC is the volume of plasma from which a substance is cleared by the kidneys per unit time
c) GFR is not a useful indicator of renal function
d) Creatinine is a substance that can be used to determine GFR
e) GFR is the amount of filtrate produced per unit of time
c) GFR is not a useful indicator of renal function
28
Which statement is TRUE about Body water?
a) 65% of a male's body is composed of water
b) Normally, a person has 4 liters of plasma in their blood
c) A person can live without water for 3 months
d) The Ascending limb of the loop of Henle is water permeable
e) The net water intake and water output of person per day is 0.
e) The net water intake and water output of person per day is 0.
29
Which statement is TRUE about Water handling by the nephron?
a) AQPs are only found in animals
b) AQP2 is located in the apical membrane of proximal tubule cells
c) An osmotic gradient is NOT required for water movement
d) The proximal tubules reabsorb 50% of the filtered water
e) AQP3 and AQP4 are located in the basolateral membrane of collecting duct cells
e) AQP3 and AQP4 are located in the basolateral membrane of collecting duct cells
30
Which statement is FALSE about Renal Corpuscle?
a) The renal corpuscle contains the glomerulus and the Bowman's capsule
b) Podocytes do not aid with filtration
c) The basement membrane is (-) charged to assist filtration
d) Jonah Laomu died from nephrotic syndrome
e) The endothelium of the glomerulus is fenestrated
b) Podocytes do not aid with filtration
31
renal corpuscle structure
-glomerulus-bowmans capsule (and space)-podocytes
32
How is correct protein topology achieved?
Hydrophobic and positive stretches of amino acids within a protein facilitate the orientation or 'topology'of a protein
33
filtration barrier
-fenestrated endothelium of the glomerular capillaries (freely permeable to water, ions and small solutes)-basement membrane (matrix of negatively charged proteins, charge based barrier)-podocytes (gaps between foot processes, prevents protein and large macromolcule filtration)
34
Post-translational modifications at the ER
-glycosylation (N-linked)-GPI anchors added-protein folding (mediated by molecular chaperone proteins)-assembly of protein complexes
35
Nephrotic syndrome
increased permeability of filtration barrier to proteins
36
Post-translational modifications at the golgi
-N-linked glycosylation-O-linked glycoslyation-Sulfation of sugars and some tyrosines-protein sorting
37
"Which statement is TRUE about Reabsorption/Secretion?
a) 100% of the filtered urea is reabsorbed by the nephron b) Reabsorption is the only renal process that ""recovers"" filtered substances and water
c) Secretion is not an energy intensive process
d) Normally, 95% of the filtered glucose is reabsorbed by your kidneys, unless you are a diabetic
e) Secretion is the only renal process that leads to excretion of materials and fluids"
"b) Reabsorption is the only renal process that ""recovers"" filtered substances and water"
38
glomerular ultrafiltarion pressures and net equation
-hydrostatic-oncotic (osmotic)-PUF = PGC-PBS-πGC
39
ER assisted degradation system
1. A protein (or substrate) is recognised as being non-functional ormisfolded by the same molecular chaperones that are helping to fold thatprotein.2. Next, the protein is sent out of the ER backwards through a proteintranslocation channel (translocon). This is called retrotranslocation ordislocation.3. The protein needs to be marked for degradation. This occurs throughubiquitin pathway enzymes tagging the protein with ubiquitin.4. Any sugars that were added to the protein in the ER are removed from theproteins (deglycosylation) and recycled.5. Finally, the marked proteins are threaded into a large barrel-likestructure called the proteasome, and the chemical bonds between aminoacids are broken (cleaved by enzyme proteases) releasing amino acidsand short peptides for reuse in new proteins.
40
pressures favouring filtration
-glomerular capillary hydrostaic pressure (PGC)
41
The process of membrane vesicle budding and fusion
Clathrin coated vesicles move proteins from the Golgi to the plasma membrane. vSNARE protein on vesicle binds tSNARE protein on target membrane. With Rab they force vesicle fusion with cell membrane
42
pressures opposing filtration
-Bowman's space hydrostatic pressure (PBS)-glomerular capillary oncotic pressure (πGC)
43
trans golgi network
Uses COP1, COP11 and clarathin vesicles. The trans-Golgi network is specialised for the purpose of partitioning offareas containing proteins for different destinations. ENaC and Na+K+ATPasecomplexes move to plasma membrane via constitutive pathway.
44
epithelium in the proximal tubule
-leaky absorptive epithelia
45
fluid phase endocytosis
-molecule begins in solution-particles not bound to receptors are endocytosed-a clathrin-coated endocytotic vesicle carries the endocytosed material
46
epithelium in distal tubule and collecting duct
-tight absorptive epithelia-(under hormonal control)
47
receptor-mediated endocytosis
-molecule begins in solution-the ligand attaches to receptors-a clathrin-coated endocytotic vesicle carries the endocytosed material
48
% water reabsorbed per day
99%
49
caveolae endocytosis
small indentations in the plasma membrane called caveolae can mediate clathrin-independent endocytosis
50
Apical and basolateral sorting signals
The sequences YXXϕ,NPXY, LL, and monoubiquitin are known endocytosis motifs in plasmamembrane proteins (ϕ=hydrophobic amino acid). These endocytosis motifs arerecognised by clathrin-binding adaptor protein complexes (called adaptins). The specific adaptin in clathrin-coated pits developing at the plasma membrane for endocytosis is adaptin complex 2 (AP2). AP2 is made up of 4 subunits: α and β adaptins (bind to clathrin), μ2 adaptin (binds YXXϕ) and σ2subunits.
51
% sodium reabsorbed per day
99.5%
52
% glucose reabsorbed per day
100%
53
possible protein trafficking pathways for sorting ofapical and basolateral proteins in epithelial cells
1. Direct sorting: apical and basolateral targeted proteins are sorted atthe trans-Golgi network into separate apical and basolateral destined tubularextensions or vesicles. 2. Indirect sorting: all plasma membrane proteins are packaged intovesicles at the trans-Golgi network and the vesicles ALL fuse at the basolateralmembrane. Then all the apical proteins are retrieved and targeted to the apicalmembrane.3. Random sorting: all plasma membrane proteins are packaged intovesicles at the trans-Golgi network and the vesicles randomly fuse with plasmamembrane all over the cell. Proteins in the wrong location are endocytosed andtrafficked to their correct location
54
reabsorption pathway
tubule to blood
55
experimental evidence for the direct protein sorting route
-Epithelial cells in culture, expressing basolateral and apical proteins tagged with different coloured fluorescent tags (green and blue).-Experiment: cool to 20oC to accumulate proteins at the trans Golgi network, warm up cells to 37oC and use live cell imaging to 'watch' the proteins.- VSV-G-blue and green-GPI were sorted into distinct vesicular carriers at the TGN.
56
secretion pathway
blood to tubule (from peritubular capillaries)
57
what compartments do the transferrin and immunogolbin receptors move through in epithelial cells?
After endocytosis from the basolateral membrane the transferrinreceptor moves tothe basolateral early endosome (where transferrin and iron arereleased), common endosome, and back to the basolateral membrane.IgA receptor is endocytosed from the basolateral membrane, moves to the basolateral early endosome, common endosome,then to the apical recycling endosome and from there it is delivered to the apical membrane. This is called transcytosis.
58
glomerular filtration rate (GFR)
-amount of filtrate produced per unit of time-normal value 125ml/min (180L/day)-a usual indicator of renal functioning
59
compartments for apical membrane proteins to move through in epithelial cells
Apical membrane proteins (ENaC) are traffickedto the apical early endosome. Here they will be degraded or recycled.If degraded, it will move to the late endosome,multivesicular body and then to the lysosome. If recycled it will move from the apical early endosome to the common endosome where it may mix with basolateral proteins, then it moves to the apical recycling endosome and finally back to the apical membrane
60
renal clearance (RC)
-volume of plasma from which a substance is completely cleared by the kidneys per unit of time-conc of substance in urine and plasma, and rate of urine produced must be known- C=Us x V/Ps (for substance 's')
61
define protein half life
Protein half-life describes the time that half of the original population of aprotein remains.
62
short lived protein example
cell cycle regulators (destroyed within minutes)
63
how can GFR be estimated using RC?
-RC of inulin or creatinine = GFR-these substances are not reabsored from tubule, not secreted into tubule and not metabolised
64
daily filtered load
DFL = GFR x[substance]plasma
65
long lived protein example
proteins in the lens of the eye(may last a lifetime)
66
transport maximum (Tm)
-there is a limit to the amount of a substance transported per unit time-the transport protein can saturate-the binding sites on transport proteins become staurated when the conc of the substance increases beyond a certain limit (the Tm)
67
role of lysosomes in protein degradation
- Degrade transmembrane proteins that are targeted to lysosomes as anendpoint in the endocytosis pathway,- Degrade other proteins/sugars/nucleic acids and also organelles that aretoo old or not functioning correctly.- Contain acid hydrolases - enzymes that work at acidic (low) pH to breakapart proteins, sugars and nucleic acids. Low pH is maintained by H+ andCl- being pumped into the lysosome
68
an increase in body water leads to ?
increased excretion of water by the kidneys
69
autophagy process
- A specialised form of lysosomal degradation where a double membranestructure called an autophagosome develops around an organelle or areaof cytosol that needs to be destroyed.- The autophagosome fuses with the lysosome and contents are degraded,with breakdown products released into the cytosol for recycling.- Pathway switched on during starvation.
70
a decrease body water leads to ?
increased reabsorption of water by the kidneys
71
enzymes of the ubiquitin system
-E1 activating enzyme, E2 conjugating enzyme, E3 ligase- The first enzyme (E1) activates ubiquitin using ATP and covalently links to ubiquitin. - The E1 transfers the ubiquitin to a second enzyme (E2 conjugating enzyme). - The E2 conjugating enzyme transfers the ubiquitin to a third enzyme (E3) that chooses the substrate that the ubiquitin will be attached to. This E3 ubiquitin ligase may first bind to ubiquitin and then transfer it to the protein to be degraded
72
water gains
-fluid and food (diet)-metabolically produced
73
single ubiquitin tag...
Targets protein for endocytosis
74
water losses
-sweat, faeces, urine
75
string of ubiquitins...
Targets protein to the proteosome (where it is threaded into the barrel of the proteasome and chopped up into small peptides that can be recycled by deubiquitinating enzyme on the proteasome
76
which segments of the nephron are permeable to water?
-proximal tubule-thin descending limb of LoH-Late distal tubule and collecting duct (under ADH influence)
77
Lysosome mediated degradation
-Acid hydrolases-Breaks down proteins, sugars, DNA/RNA-Somewhat random, but ubiquitin tagging needed for some substrates.-Mainly cell surface and extracellular proteins (except autophagy). Molecules endocytosed
78
what are aquaporins?
a family of plasma membrane proteins that form channels permitting a high rate of water flow
79
Proteosome mediated degradation
-Peptidases-Breaks down proteins, ubiquitin recycled-Highly regulated-Requires a series of three enzymes: E1, E2 and E3-Cytosolic, nuclear, ER proteins (ERAD)
80
how much water do the proximal tubules receive per day?
180L
81
Autophagy mediated degradation
-Acid hydrolases-Breaks down damaged organelles, microbes, protein aggregates, and bulk cytosolic components-Regulated and random-Cytosolic-Double-membrane structure
82
how much water do the proximal tubules reabsorb?
67% (120L)
83
mechanisms of water movement through the PT?
both paracellular and transcellular
84
how much water to the thin descending limbs of LoH reabsorb?
16% of FL (30L)
85
how much water to the late distal tubules reabsorb?
5-10% of FL (10-20L)
86
how much water to the collecting ducts reabsorb?
8% of FL (15L)
87
where is AQP1 found?
-proximal tubules and thin descending limb-apical and basolateral membranes
88
where is AQP2 found?
-late distal tubule and collecting duct-apical membrane
89
where are AQPs 3 and 4 found?
-late distal tubule and collecting duct-basolateral membrane
90
which AQP is always regulated by ADH?
AQP2
91
what is ADH?
-hormone produced in hypothalamus-released when body osmolarity increases or plasma volume decreases-stored and released from posterior pituitary
92
ADH mode of action
-bind to V2 receptor on BL membrane of LDT and CD cells-activates adenylate cyclase which increases cAMP levels-cAMP activates PKA-phosphorylation of sub-apical AQP2 vesicles results in them moving to apical membrane and be incorporated via exocytosis-increases apical membrane H2O permeability
93
what is diabetes insipidus?
disease characterised by excessive and dilute urination, due to reduced water reabsorption
94
causes of central DI
failure to produce ADH by the hypothalaus or secrete from the posterior pituitary gland
95
causes of nephrogenic DI
-mutation of AQP2 channel-mutation of V2 receptor(a problem at the level of the kidney)
96
normal blood pressure
120/80
97
source of Na+
dietary
98
losses of Na+
-sweat, faeces, urine,-also vomit, diarrhea and menstruation
99
sodium in ECF
150mM
100
sodium in ICF
10mM
101
daily filtered load of sodium
180L/day x 150mmol/L = 27000 mmol/day
102
what parts of the nephron are permeable to sodium?
-proximal tubule-thin and thick ascending limb of LoH-distal tubule-collecting duct
103
how much sodium do the proximal tubules receive per day?
27000mmol
104
how much sodium do the proximal tubules reabsorb?
67% of FL (18000mmol)
105
Na+ coupled transporters in the apical membrane of the PT?
-Na+-glucose cotransporters (SGLT)-Na+/H+ exchangers-Na+-amino acid cotransporters
106
location of SGLT2
proximal convoluted tubule
107
SGLT2 characteristics
-low affinity for glucose but high capacity-1Na+:1 glucose stoichiometry
108
location of SGLT1
proximal straight tubule
109
SGLT1 characteristics
-high affinity for glucose but low capacity-2:1 Na+:glucose stoichiometry
110
SGLT 1 and 2 inhibitor
phloridzin
111
types of Na+/H+ exchangers in kidney
-NHE1,2,3,4-NHE3 is dominant isoform
112
NHE function
-moves Na+ down concentration gradient for exchange of H+ up its concentration gradient-also used in pH balance
113
how much sodium do the thick and thin ascending limbs reabsorb?
25% of FL (6750mmol)
114
what transporter is found in the thick and thin ascending limbs (apical membrane)?
Na+-K+-2Cl- cotransporter (NKCC2)
115
gradients in NKCC2
Na+ and Cl- move down concentration gradient, K+ moves against gradient
116
NKCC2 selectively inhibited by...?
'loop diuretics' bumetanide and frusemide
117
how much sodium do the distal tubules reabsorb?
5% of FL (1350mmol)
118
which transporter is found in the early distal tubule?
Na+-Cl- cotransporter (NCCT)
119
which transporter is found in the late distal tubule and collecting duct?
ENaC
120
NCCT molecular similarity to NKCC2
60%
121
NCCT inhibitor
thiazide diuretics
122
Apical ENaC inhibitor (blocker)
amiloride
123
ENaC compostion and characteristics
-3 subunits (α:β:γ) which together make a functional channel-each subunit has 2 transmembrane domains, and a large extracellular loop-PY motif (PPPXY) on C-termini - important in protein-protein interactions-normally, Nedd-4-2 leads to an increase ubiquitylation of ENaC-regulated by aldosterone
124
Liddle's syndrome (ENaC)
-gain of ENaC function due to mutations of COOH-termini of β and γ subunits (the channel remains at the membrane indefinately)-too many channels-hypertension due to increased Na+ reabsorption-hypokalemic (increased K+ secretion)-metabolic alkalosis
125
Pseudohypoaldosteronism type 1 (ENaC)
-loss of function due to a mutation of the NH2-terminus of the α subunit-too few channels
126
factors affecting tubular reabsorption of Na+
-changes in Starling forces (hydrostatic and osmotic pressures)-renin-angiotensin-aldosterone system-renal nerve activity-prostaglandins-ANP-inhibitors of Na+/K+ ATPase
127
what happens to PGC, GFR and RBF if the afferent arteriole constricts?
all decrease
128
what happens to PGC, GFR and RBF if the efferent arteriole constricts?
-PGC and GFR increase-RBF decreases
129
what happens to PGC, GFR and RBF if a telescope shape is formed (afferent more constricted and efferent more dilated)?
-PGC and GFR decrease-RBF increases
130
Which statement is TRUE about Na+ Homeostasis?
a) The ECF Na+ concentration is 170mM
b) Normal blood pressure is 150/90 mmHg
c) If you have a high NaCl diet, you will excrete more Na+ than normal
d) All segments of the nephron can reabsorb Na+
e) The ICF Na+ conc is 50mM
c) If you have a high NaCl diet, you will excrete more Na+ than normal
131
"Which statement is FALSE about Na+ Homeostasis?
a) The proximal tubule is the ""Powerhouse"" of the Nephron
b) 100% of filtered glucose is reabsorbed by the SGLT2 and SGLT1 of the proximal tubule cells
c) If you have a high NaCl diet, you will excrete more Na+ than a person who has a NaCl normal.
d) SGLT2 has a higher affinity for glu than SGLT1
e) NHE3 is the dominant Na+/H+ exchanger isoform of the apical membrane of proximal tubule cells"
d) SGLT2 has a higher affinity for glu than SGLT1
132
Which statement is TRUE about Thin and Thick Ascending Loop of Henle and Distal Tubule?
a) Cells of the Thin and Thick Ascending Loops of Henle reabsorbs 30% of the filtered Na+
b) The Na+,Cl- cotransporter is the main transport protein that secrets NaCl by the Thin/Thick Ascending Limbs
c) The Na+,K+,2Cl cotransporter is inhibited by Thiazide diuretics
d) The cells of the distal tubule reabsorb 5% of the filtered Na+
e) The early and late distal tubule cells use ENaC to reabsorb Na+ from the filtrate.
d) The cells of the distal tubule reabsorb 5% of the filtered Na+
133
24. Which statement is FALSE about Na+ Homeostasis?a) Fine-tuning of Na+ reabsorption occurs in the Late Distal Tubule and Collecting Duct cells of the nephron
b) 100% of filtered glucose is reabsorbed by the SGLT2 of the proximal convoluted tubule cells
c) If you have a low NaCl diet, you will excrete less Na+ than a person who has a NaCl normal
d) The Thin descending limb of Loops of Henle is not permeable to Na+
e) NHE3 is the dominant Na+/H+ exchanger isoform of the apical membrane of proximal tubule cells
b) 100% of filtered glucose is reabsorbed by the SGLT2 of the proximal convoluted tubule cells
134
what happens to PGC, GFR and RBF if a backwards telescope shape is formed (efferent more constricted and afferent more dilated)?
all increase
135
the parts of the juxtaglomerular apparatus
-macula densa cells of the thick ascending limb-granular cells on the smooth muscle of the afferent arteriole
136
macula densa cells function
osmoreceptor function
137
granular cells function
-baroreceptor function-produces renin (and angiotensin 11)
138
renin-angiotensin-aldosterone system
-renin produced and released from granular cells of JGA-renin cleaves angiotensinogen into Ang 1, which is cleaved by ACE into Ang 11-Ang 11 stimulates release of aldosterone by the zona glomerulosa cells in the adrenal cortex-aldosterone increases Na+ reabsorption at the level of the late distal tubule and collecting duct
139
what type of hormone is aldosterone?
mineralocorticoid hormone
140
aldosterone action phase 1
-'latent period', 0.5-1 hour-de novo protein synthesis; induce proteins
141
aldosterone action phase 2
-'early response', 1.5-3 hours-activation of pre-existing Na+ channels and Na+/K+ ATPases
142
aldosterone action phase 3
-'late response', 6-24 hours- induction of 'new' Na+ channels and Na+/K+ ATPases
143
Which of the following statements is TRUE about Na+ Reabsorption?
a) The macula densa cells function as baroreceptors
b) Aldosterone is a steroid hormone and binds to a receptor on the basolateral membrane of Late distal tubule and Collecting duct cells
c) Angiotensin II is cleaved by renin to produce Angiotensin I
d) Renin is released from the granular (juxtaglomerular) cells of the afferent arteriole
e) Osmoreceptors of the adrenal cortex monitor blood pressure
d) Renin is released from the granular (juxtaglomerular) cells of the afferent arteriole
144
[K+] in ECF
4mM
145
[K+] in ICF
150mM
146
Hyperkalemia?
ECF [K+] >5 mM (>10 =death)
147
Hypokalemia?
ECF [K+] <3.5mM(<2.5 =death)
148
why is a high ICF [K+] important?
-maintain cell volume-regulation of pH-contolling enzyme function-controlling DNA and protein synthesis-controlling cell growth, cell cycling and cell proliferation
149
extrarenal factors that the body uses to maintain K+ homeostasis
-epinephrine-insulin-aldosterone(prevents hyperkalemia)
150
why is a low ECF [K+] important?
-maintain the steep K+ gradient across the membrane to maintain the potential of cells-low K+ prevents problems with excitation and contraction (action potential, muscle contraction, cardiac rhythmicity)
151
intrarenal factors that the body uses to maintain K+ homeostasis
-regulation of reabsorption and secretion of K+ along the nephron
152
What do epinephrine, insulin and aldosterone do to the activity of Na+/K+ ATPase?
increase it
153
where is epinephrine released from?
chromaffin cells of adrenal medulla
154
K+ reabsorption in the proximal tubule
-reabsorbs 67% FL-mainly through paracellular pathway
155
K+ reabsorption the thick ascending limb
-reabsorbs 20% FL-via cellular (NKCC2) and paracellular pathways
156
the cells and their function in the cortical collecting duct
-intercalated cells (30%), K+ reabsorption-principal cells (70%), Na+ reabsorption and K= secretion
157
K+ reabsorption in the intercalated cells of the cortical collecting duct
-reabsorbs 9% FL-via K+/H+ ATPase
158
K+ secretion in the principal cells of the cortical collecting duct
-through luminal K+ channel-under influence of aldosterone and K+Cl- cotransporter
159
If you have low K+ diet, which of the following statement is TRUE?
a) Your body would increase K+ secretion by the collecting duct cells
b) Your body would increase the release of aldosterone from the adrenal cortex
c) Your body would increase the release of epinephrine to increase uptake of K+ into cells
d) Your body would reduce insulin release to reduce uptake of K+ into cells
e) Your body would increase the amount of Angiotensin II
d) Your body would reduce insulin release to reduce uptake of K+ into cells
160
hyperkalemia causes....
-stimulates adrenal cortex (aldosterone)-activates Na+/K+ ATPase which increases intracellular K+ resulting in increased exit of K+ across the apical membrane (secretion by cells of the LDT and CD)
161
effect of aldosterone on K+ secretion by LDT and CD
-increade activation and amount of ENaC-increase amount of activity of Na+/K+ ATPase (entry of K= across basolateral membrane)-entry of sodium makes cell potential more positive, enhancing the driving force for K+ to exit across apical membrane (secretion)
162
effect of flow on K+ secretion
a low K+ diet causes a low flow rate of tubular fluid, which means K+ secretion is also low
163
Which of the following statements is TRUE about K+ Homeostasis?
a) A typical diet does not contain the proper amount of daily K+
b) Low ICF K+ is very important for proper enzyme function
c) An ECF concentration of 6.2mM is normal
d) K+ is not involved in the nerve action potential
e) K+ is the most abundant cation in the body
e) K+ is the most abundant cation in the body
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cause of rickets
a deficiency or impaired metabolism of vitamin D, calcium or phosphorus
165
calcium concentration in body
- bone and teeth 99%-ICF <0.1 μm-ECF 2-3mM
166
ECF calcium >3mM
hypercalcemia
167
ECF calcium <2mM
hypocalcemia
168
why is it important to maintain appropriate ICF and ECF concentrations of calcium?
-proper bone function-neurotransmission-mitosis, cell division and growth-muscle contraction-blood clotting-growth-enzymatic reactions-2nd messener function
169
effects of hypocalcemia
-increase excitability of nerve cells and muscle cells-pins and needles-airway obstruction-epileptic seizures-cardiac arrhythmias-hypocalcemia tetany (muscle spasms)
170
effects of hypercalcemia
-decrease excitability of nerve cells and muscle cells-disorientation-lethargy-cardiac arrhythmias-death
171
Which of the following statments is TRUE about Ca2+ Homeostasis?
a) The bulk Ca2+ in the body is located within the ICF
b) Low ECF Ca2+ causes decreased excitability of nerve cells
c) The ECF Ca2+ conc. is btw 2-3mM
d) osteoporosis causes an increase in bone masse) With a high Ca2+ diet, your daily Ca2+ intake would equal your daily Ca2+ excreted
c) The ECF Ca2+ conc. is btw 2-3mM
172
types of calcium in the plasma
-ionized (50%)-bound to protein (usually albumin) (40%)-complexed with anions (10%)
173
how much of the plasma calcium can be filtered?
60%
174
Ca2+ reabsorption in the proximal tubule
-reabsorbs 50-60% FL-100% via paracellular pathway
175
Ca2+ reabsorption in the thick ascending limb
-reabosrbs 15% FL-claudin-16 plays a role in maintaining the permeability of the TJ that favours transport of Ca2+, Mg2+ and Na+
176
what does the calcium sensing receptor do?
-monitors the ECF Ca2+ concentration-found on membrane of chief cells
177
Ca2+ reabsorption in the distal convoluted tubule
-reabsorbs 10-15% FL-uses many Ca2+ transporters-claudin-8 is a TJ protein which prevents th movement of Ca2+-Ca2+ channel entry and exit via Ca2+-ATPase and Na+/Ca2+ exchanger (NCX1)
178
Which of the following statements is FALSE about Ca2+ Homeostasis?
a) 50% of Ca2+ in plasma is ionized
b) 60% of the blood Ca2+ can be filtered at the glomerulus
c) The proximal tubule reabsorbs 50-60% of the filtered Ca2+
d) Ca2+ sensing receptor monitor the intracellular Ca2+ concentratione) Calbindin is a Ca2+ binding protein that helps to transport Ca2+ across a tubule cell
d) Ca2+ sensing receptor monitor the intracellular Ca2+ concentration
179
Parathyroid hormone
-stimulated by low plasma Ca2+ levels-stimulates bone resorption (releases Ca2+ into plasma)-stimulates reabsorption of Ca2+ by TAL and DT-increases the release of calcitriol
180
Calctriol
-form of activated vitamin D-released under PTH influence due to low calcium-stimulates resorption of bones (releases Ca2+ into plasma)-stimulates reabsorption of Ca2+ by DT-stimulates Ca2+ absorption by intestine-has negative feedback control on the parathyroid gland to regulate release of PTH
181
"Which of the following statements is FALSE about Ca2+ Homeostasis?
a) The kidney, bone and intestine all play roles in Ca2+ homeostasis
b) The parathyroid hormone is released by high plasma Ca2+
c) Calcitriol is ""activated vitamin D3""
d) Parathyroid hormone stimulates resorption of bonee) Calcitriol stimulates reabsorption of Ca2+ by cells of the distal tubule"
b) The parathyroid hormone is released by high plasma Ca2+
182
symptoms of diabetes insipidus (DI)
-polyuria-polydipsia-1st year of life --> vomiting, fever, slow growth, developmental delay-severe dehydration-in severe cases --> mental deficiency due to dehydration of the brain
183
types of nephrogenic DI
-congenital X-linked (mutated V2 receptor)-Autosomal (mutated AQP2 channel)
184
How many NDI patients have congenital X-linked NDI?
90% (normally males)
185
How many NDI patients have autosomal NDI?
10%
186
How many mutations in congenital NDI (V2 receptor mutation)?
~200
187
How many mutations in autosomal NDI (AQP2 mutation)?
53
188
Effects of Mutations of the V2 receptor and AQP2?
-loss of function-ineffective biosynthesis of protein-simple binding impairment of V2 receptors-intracellular trafficking problems-accelerated degradation by the proteosome or lysosome
189
Which of the following statement is TRUE?
a) Vasopressin is produced in the supraoptic and paraventricular nuclei of the posterior pituitary gland
b) Central DI is a problem with vasopressin production, storage and release from the hypothalamus
c) Nephrogenic DI is a problem at the level of the Late distal tubule and Collecting duct
d) Individuals with NDI exhibit reduced urine production
e) Congenital X-linked NDI is a problem with 10% of NDI patients
b) Central DI is a problem with vasopressin production, storage and release from the hypothalamus
190
What is Bartter's syndrome?
-autosomal recessive disorder-1:50000 to 1:100000 births-salt washing (NaCl loss in urine)-hypereninism and hyperaldosteronismmetabolic alkalosis-hypokalemia
191
Bartter's syndrome occurs when there is a problem with the transport proteins of epithelial cells in which part of the nephron?
thick ascending limb of LoH
192
Which transporter is affected in Bartter's syndrome type 1?
apical Na+-K+-2Cl- contransporter (NKCC2)
193
Which transporter is affected in Bartter's syndrome type 2?
apical K+ channel (ROMK1)
194
Which transporter is affected in Bartter's syndrome type 3?
basolateral Cl- channel (CLCNKB)
195
mutations of NKCC2, ROMK1 and CLCNKB
-non-functional channels/cotransporters-ineffective biosynthesis of protein-simple binding impairment of NKCC2-intracellular trafficking problems-accelerated degradation
196
Which of the following statement is TRUE about Bartter's syndrome?
a) Bartter's syndrome type 3 is a problem with Distal tubule
b) BS patients exhibit hyporeninism and hypoaldosteronism
c) BS1 patients have a mutations of the Na,K,2Cl cotransporter
d) BS3 patients exhibit hyperkalemia
e) BS1 patients exhibit metabolic acidosis
c) BS1 patients have a mutations of the Na,K,2Cl cotransporter
197
Reasons for Liddle's syndrome symptoms: principal cell
-increased Na+ reabsorption leads to increased negative luminal voltage-this leads to increased K+ secretion, hence, hypokalemia
198
Reasons for Liddle's syndrome symptoms: intercalated cell
-increased luminal negative voltage causes H+ secretion and HCO3- recycling -hence, metabolic alkalosis (increased H+ loss and gain of HCO3-)
199
tests for DI
-water deprivation test-injection of dDAVP; synthetic ADH-Plasma antidiuretic hormone levels
200
normal GFR
125 mL/min
201
what does normal plasma glucose not usually exceed? What will happen if this gets any higher and why?
150mg/100ml. If any higher the person will have diabetes, because the SGLT will meet the transport max and not be able to reabsorb all of the filtered load, so glucosuria will occur.
202
Which of the following statement is FALSE about Liddle's Syndrome?
a) Liddle's syndrome patients have hypokalemia
b) The number of ENaC channels at the apical membrane are increased in patients who have Liddle's syndrome
c) SGK aids in maintaining ENaC at the apical membrane
d) The R556X mutation of ENaC results in too many ENaC channels at the apical membrane of cells of the collecting duct
c) SGK aids in maintaining ENaC at the apical membrane
