Physio Flashcards
1
Q
What are the 2 types of functional units in the kidney?
A
Cortical and Juxtamedullary nephrons
2
Q
The cortex contains __________ of nephrons.
The medulla contains ________ of nephrons.
A
Cortex: Bowman’s capsule, PCT, DCT
Medulla: Loops of Henle, Collecting ducts
3
Q
What are the components of the Renal corpuscle?
A
Bowman’s capsule + glomerulus
4
Q
What are the blood vessels that run adjacent to nephrons?
A
Vasa recta (peritubular capillaries dipping into the medulla)
5
Q
In which part of a nephron does filtration occur?
A
Glomerulus/Bowman’s capsule
6
Q
In which part of a nephron does reabsorption?
A
Every part (except bowman’s capsule) but primarily in the PCT
7
Q
In which part of a nephron does secretion occur?
A
PCT, DCT, collecting duct
8
Q
In which part of a nephron does excretion occur?
A
End of collecting duct
9
Q
What % of filtered volume leaves the loop of henle?
A
10%
10
Q
What % of filtered volume leaves the collecting duct?
A
0.8% (1.5L/day)
11
Q
Describe the changes in osmolarity as filtrate moves through the nephron.
A
Bowman’s capsule: 300mOsm (normal)
Start of Loop: 300
Mid Loop: 1200
End Loop: 100
End of collecting duct: variable depending on Aldosterone/ADH
12
Q
↑Describe the changes in filtered volume as fluid moves through the nephron.
A
~20% of plasma passing through the glomerulus is filtered
~1% leaves (19% reabsorbed)
PCT: 70% of filtrate reabsorbed
Loop: 20% reabsorbed
By end of Collecting duct: <1% left
13
Q
How does ultrafiltration occur?
A
High hydrostatic pressure in the glomerular capillaries
- mesangial cells can contract to ↑P
→ fluid passes through fenestrations in capillaries and through filtration slits between podocytes
14
Q
What are the 3 layers of the glomerular filtration barrier?
A
1) Glomerular capillary endothelium
2) Basal lamina
3) Bowman’s capsule epithelium (podocytes)
15
Q
What are the pressures influencing ultrafiltration at the renal corpuscle?
A
1) Hydrostatic/Blood pressure (55mmHg) favors filtration (higher in capillaries)
2) Colloid osmotic pressure (30mmHg) opposes filtration (more proteins in capillaries)
3) Hydrostatic pressure in bowman’s capsule (15mmHg) opposes filtration
16
Q
What are the 2 main factors influencing GFR?
A
1) Net filtration pressure:
Hydrostatic - Colloid osmotic - fluid pressure
2) Filtration coefficient
- SA of glomerular capillaries
- permeability of 3 layers of filtration barrier
17
Q
Describe how autoregulation of GFR occurs over a wider range of BPs.
A
Decreased GFR → constrict AA, dilate EA
Increased GFR → dilate AA, constrict EA
18
Q
In renal artery stenosis,
GFR _____
Serum creatinine _____
K+ ______
±Edema
BP____
A
↓ Glomerular capillary pressure:
GFR ↓
Serum creatinine ↑
Hyperkalemia
Edema
BP ↑
19
Q
What are the 3 causes of acute renal failure?
A
1) Prerenal
- ↓ BP/disrupted blood flow
2) Intrarenal
- Kidney damage
3) Postrenal
- Sudden obstruction of urine flow
20
Q
How does the afferent arteriole constrict in response to increased GFR?
A
1) GFR ↑
2) Flow past macula densa ↑
3) Macula densa paracrine signaling to JG cells
4) JG cells contract to constrict afferent arteriole
21
Q
What is the difference between transcellular and paracellular transport in tubule epithelial cells of the kidney?
A
Transcellular: cross apical and baso-lateral membranes of cells
Paracellular: cross through intercellular junctions
22
Q
Which substance(s) only move(s) out of the nephron tubule lumen by transcellular transport?
A
Na+ active transport
23
Q
Which substance(s) move(s) out of the nephron tubule lumen by both paracellular and transcellular transport?
A
1) Anions
2) Water
3) Permeable solute (K+, Ca2+, urea)
24
Q
How do sodium transport on the apical and basolateral surface of PCT cells differ?
A
Apical: passive (ENaC)
Basolateral: active (Na+/K+ exchanger)
25
How does the Na+/K+ ATPase work?
1) 3 Na+ enters protein on cytosolic side
2) ATP hydrolysis → protein linked with P
3) Protein opens of extracellular side → release 3 Na+
4) 2 K+ binds to protein, P released
5) 2 K+ released into cytosol
26
How is glucose transported out of the nephron tubular lumen?
Apical: Secondary active transport with Na+ (SGLT symport)
Basolateral: simple/facilitated diffusion (GLUT)
27
Does glucose filtration rate in the kidney saturate with increasing plasma glucose concentration?
No, it is proportional to plasma concentration
28
What is the relationship between glucose reabsorption and plasma concentration?
Positive direct (reabsorption=Pc) UNTIL transport max (375mg/min)
(transporters are saturated)
## Footnote
100% of filtered glucose is reabsorbed up till ~300mg/dL
29
What is a renal threshold?
Plasma concentration of a solute at which transport/reabsorption is at its maximum
30
Glucoses excretion is zero until _______.
Plasma glucose > renal threshold
31
How is urea reabsorbed in the kidney?
Passive diffusion
1) Filtrate Urea conc. = ECF
2) Reabsorption of Na+ → Water osmosis → Urea gradient towards ECF
3) Urea passively diffuses across tubular epithelium (apical surface)
32
How are plasma proteins reabsorbed in the kidney?
Endocytosis → transcytosis
1) Proteins endocytosed and digested by lysosomes
2) Released as amino acids via transcytosis out of basolateral surface
## Footnote
Only small peptides and enzymes pass through filtration barrier
33
What is Fanconi syndrome?
Dysfunctional PCT
34
Where are organic anions secreted in the nephron?
PCT
35
How are organic anions secreted in the nephron?
1) Na+/K+ ATPase → ↓Intracellular [Na+] (Direct active)
2) NaDC (Na+/Dicarboxylate symport) → ↑ Intracellular [dicarboxylate]
3) OAT (basolateral organic ion/Dicarboxylate antiport) → ↑ Intracellular [OA-]
4) Organic ions enter via facilitated diffusion (exchange with OA-)
36
What is the units of clearance?
ml/min
37
What is the definition of clearance?
Amount of plasma (ml) cleared of a solute
38
How do you tell if there is net reabsorption of a substance?
Clearance
39
How do you tell if there is net secretion of a substance?
Clearance>GFR
40
What is an example of a substance that is net reabsorbed?
Urea
41
What is an example of a substance that is net secretion?
Penicillin
42
What are 2 substances that have no net secretion/reabsorption?
Inulin and Creatinine
43
Why is inulin not used to estimate GFR?
It does not occur normally in the body
44
Why is creatinine used to calculate GFR?
Production and breakdown of phosphocreatine (source of creatinine) relatively constant
→ Pc of Cr does not vary much
45
How is creatinine clearance calculated?
Urine Cr (mg/dL) X Urine vol. (ml/min) / Serum Cr (mg/dL)
46
The fluid within renal cortex is (more/less) concentrated than the medulla.
Less
Cortex is isosmotic to plasma.
Medulla becomes progressively concentrated
47
How does the osmolarity of filtrate change throughout a nephron?
1) PCT reabsorbs both solutes and water: no change in osmolarity
2) Descending limb: only water reabsorbed → ↑ Osmolarity
3) Ascending limb: only solutes/salts → ↓ Osmolarity
4) DCT reabsorbs both solutes and water: no change in osmolarity
5) Permeability of collecting tubule varies w ADH
48
What are 3 stimuli that stimulate Vasopressin secretion?
1) ↓BP (Carotid/aortic baroreceptors)
2) ↓Atrial stretch/↓blood vol (atrial stretch receptor)
3) Osm>280mOsm (hypothalamic osmoreceptors)
49
How is Vasopressin released?
1) ADH made and packaged in hypothalamic neuron cell body
2) ADH-containing vesicles transported down and stored in posterior pituitary gland
3) Released into blood
50
What is the T1/2 of ADH?
15mins
51
What is the moa of ADH?
Targets renal collecting duct
1) Binds to basolateral receptor
2) Activates cAMP messenger system
3) Triger exocytosis of AQP2-containing vesicles → ↑ aquaporin in apical membrane
52
What is the relationship between plasma vasopressin conc. and plasma osmolarity?
Positive direct relationship
53
What is the treatment for nocturnal enuresis?
Desmopressin (vasopressin derivate)
54
How is nocturnal enuresis normally prevented and compromised in enuretic children?
Normally, vasopressin secretion follows circadian rhythm → ↑ at night
In enuretic children, vasopressin secretion doesn't increase at night
→ ↑ urine output
→ spontaneous emptying during sleep
55
What is Diabetes Insipidus?
Damage of hypothalamus → inability to produce ADH
→ ↓ permeability of collecting ducts to water
→ excessive water loss
56
What is SIADH (Schwartz-Bartter Syndrome)?
Syndrome of Inappropriate ADH secretion
→ Excessive release of ADH
→ Volume overload and HypoNa+
57
In what form of cancer is SIADH commonly seen?
Small cell lung carcinoma
58
What is the countercurrent exchange system and what is its benefit?
Countercurrent between the closely associated Vasa Recta and Loop of Henle
- Filtrate in descending limb becomes progressively more concentrated as water moves into the vasa recta (opp. directions means lower down still have water potential gradient)
- Ascending limb becomes less concentrated as more solutes are actively reabsorbed (opp. direction means vasa recta gets more concentrated for osmosis in descending limb)
59
What is the the different between osmolarity and tonicity?
Osmolarity: Solutes/L of solution (Osm/L)
Tonicity: How a solution affects cell vol. (no units)
60
Tonicity depends of the relative concentration of (penetrating/non-penetrating) solutes.
Non-penetrating
61
All that apply: A hypoosmotic solution can be (hypotonic, isotonic, hypertonic).
Only hypotonic
(tonicity is a "subset" of osmolarity since it depends on conc. of non-penetrating solutes)
62
All that apply: A isoosmotic solution can be (hypotonic, isotonic, hypertonic).
Isotonic and Hypotonic
(Some may not be able to equilibrate)
63
All that apply: A hyperosmotic solution can be (hypotonic, isotonic, hypertonic).
Hypotonic, isotonic, hypertonic
(depending on relative conc. of non-penetrating solutes)
64
What type of solution is given for px with intracellular dehydration (eg. Diabetes Insipidus, Dehydration)?
Hypotonic solution
eg. 0.45% Saline (Half normal saline)
65
What type of solution is given for px with ECF depletion (eg. hypovolemia)?
Isotonic solution
eg. 0.9% Saline (Normal saline)
66
How does drinking a large amount of water affect blood volume and osmolarity?
↑ volume, ↓ osmolarity
67
How does drinking water throughout prolonged vigorous excercise affect blood volume and osmolarity?
No change in volume, ↓ osmolarity
68
How does dehydration affect blood volume and osmolarity?
↓ volume, ↓ osmolarity
69
How does 9% Saline affect blood volume and osmolarity?
↑ volume, no change in osmolarity
70
How does bleeding/haemorrhage affect blood volume and osmolarity?
↓ volume, no change in osmolarity
71
How does drinking sea water affect blood volume and osmolarity (immediately)?
↑ volume, ↑ osmolarity
72
How does excessive sweating/diarrhoea affect blood volume and osmolarity?
↓ volume, ↑osmolarity
73
What are the homeostatic responses to salt ingestion?
↑osmolarity → detected by osmoreceptors
1) ADH secreted from posterior pituitary → ↑ aquaporin in collecting ducts
→ ↑water reabsorption
2) Thirst → ↑ water intake
74
What is the most important stimulus for thirst?
Osmoreceptor input
75
Where is aldosterone made?
Adrenal cortex
76
What is the T1/2 of aldosterone?
15mins
77
What are 2 stimuli that induce aldosterone secretion?
1) ↓BP (via renin)
2) ↑K+
78
What is 2 stimuli that inhibits aldosterone secretion?
1) Very high osmolarity
2) Natriuretic peptides (inhibit ATII)
79
What are the target receptors and cells of aldosterone?
Cytosolic Mineralocorticoid Receptors on Principal cells in the distal nephron and renal collecting duct
80
What is the moa of aldosterone?
1) Aldosterone binds to cytosolic MC receptor
2) Hormone-receptor complex initiates protein synthesis of new ion channels (ENaC, ROMK) and pumps (Na/K ATPase)
3) Aldosterone-induced proteins modulate existing pumps/channels
↑ Na+ reabsorption+ ↑K+ secretion → ↑water reabsorbed
81
True or false. Na+ reabsorption is automatically coupled with water reabsorption in the PCT, DCT and collecting duct.
PCT: automatically coupled
DCT: requires aldosterone
Collecting duct: requires aldosterone/ADH
82
True or false. Distal tubular water reabsorption occurs at all times, regardless of hormonal regulation as long as filtration is not affected.
False.
Distal tubular water reabsorption requires vasopressin
83
What hormone is activated when there is an acute increase in blood osmolarity?
ADH → ↑water reabsorption → ↓osmolarity
84
What hormone is activated when there is an acute loss of isotonic blood volume?
Aldosterone → ↑Na+ reabsorption + ↑ K+ secretion
85
Which part of the nephron does acetazolamide act on?
PCT
86
Which part of the nephron do Osmotic diuretics (eg. mannitol) act on?
PCT + Descending limb of LoH
87
Which part of the nephron do Loop diuretics (eg. Furosemide) act on?
Ascending limb of LoH
88
Which part of the nephron do Thiazides (eg. HCTZ) act on?
DCT
89
Which part of the nephron do Potassium-sparing diuretics (eg. spironolactone) act on?
DCT
90
What are 5 examples of loop diuretics?
ET is FABulous
1) Ethacrynic acid
2) Torsemide
3) Furosemide
4) Azosemide
5) Bumetanide
91
What are 3 clinical indications for loop diuretics?
HE
1) HF
2) HTN
3) Edema
92
What are 4 AEs of loop diuretics?
HypO
1) Hyponatremia
2) Hypokalemia
3) Hypomagnesemia
4) Ototoxicity
93
What is the most dangerous complication/sequelae of hyperkalemia?
Cardiac arrythmias, ↑ excitability of neurons/skeletal muscles
94
What is the physiological response to hyperkalemia?
↑ Aldosterone → ↑K+ secretion
95
What is the most dangerous complication/sequelae of hypokalemia?
Muscle weakness → failure of respiratory and heart muscles
96
What is the physiological response to hyperkalemia?
↓ /No Aldosterone → no secretion of K+ into collecting ducts
97
Where is ACE located?
Capillary endothelium
98
What organ produces angiotensinogen?
Liver
99
Where does renin come from?
JG cells of kidneys
100
What is the rate limiting factor in the RAAS pathway?
Plasma renin concentration
101
What stimulates renin secretion?
↓Na+
↓BP
102
What is the direct chemical stimulus for aldosterone secretion?
Angiotensin II
103
What are the 4 systemic mechanism/responses to dehydration?
Dehydration: ↓BP/vol + ↑osmolarity
1) CVS
- detected by carotid/aortic baroreceptor → cardiovascular center
→ ↑sympathetic + ↓parasympathetic
→ ↑heart rate and contractility + vasoconstriction
→ ↑ CO + ↑BP
2) RAAS
- detected by macula densa → paracrine to JG cells
→ renin → AT1 → AT2 (by ACE)
→ ↑ CVS response + ↑ thirst + ↑aldosterone (but inhibited by ↑Osm)
→ ↓Na+ reabsorption (DCT + collecting duct) → ↓ osmolarity
3) Renal mechanisms
- ↓ GFR → volume conserved
4) Hypothalamus
- detected by atrial stretch, carotid/aortic baroreceptors, hypothalamic osmoreceptors
→ ↑thirst + ↑ADH release from posterior pituitary
→ ↑water intake + ↑water reabsorption
104
Where do natriuretic peptides come from?
Myocardial cells
↑blood volume → myocardial stretch and release ANP/BNP
105
What is BNP used for?
Indicator for HF (only ventricular stretch causes release by ventricle myocardium)
106
What is the overall effect of natriuretic peptides?
↑ salt and water excretion
(anti-aldosterone)
107
What are 4 specific tissue actions of natriuretic peptides?
1) Afferent arterioles
- vasodilate → ↑GFR
- inhibit renin secretion
2) Nephron
- ↓Na+ and water reabsorption
3) Adrenal cortex
- inhibit aldosterone secretion
4) Hypothalamus
- inhibit ADH secretion
5) Medulla oblongata
- ↓sympathetic output
108
What are the receptors and responses to ↓BP/volume?
1) Direct: ↓GFR
2) Macula densa → JG cells → renin
3) Carotid/aortic baroreceptors → CVCC → ↑SNS ↓PNS
4) Carotid/aortic baroreceptors + atrial volume receptors → ↑thirst + ↑ADH secretion by posterior pituitary
109
What are the receptors and responses to ↑BP?
1) Direct: ↑GFR
2) Myocardial cells → ANP/BNP
3) Carotid/aortic baroreceptors → CVCC → ↓SNS ↑PNS
4) Carotid/aortic baroreceptors + atrial volume receptors → ↓thirst + ↓ADH secretion by posterior pituitary
110
What are the receptors and responses to ↑blood osmolarity?
1) Adrenal cortex → ↓aldosterone
2) Hypothalamic osmoreceptors → ↑thirst + ↑ADH secretion from posterior pituitary
111
What are the receptors and responses to ↓blood osmolarity?
1) HypoNa+ → Adrenal cortex → ↑aldosterone
2) Hypothalamic osmoreceptors → ↓ADH secretion from posterior pituitary
112
A 0.3 change in pH corresponds to a change in [H+] by what factor?
2
113
A decrease in pH of 1 unit corresponds to a ______ increase in [H+].
10x
114
What is the normal range of blood pH?
7.38-7.42
115
Acidosis causes neurons to be _____ and can lead to ______.
less excitable
CNS depression
116
Alkalosis causes neurons to be (hyper/lessexcitable)
Hyperexcitable
117
What are 3 components of pH homeostasis?
1) Buffers (eg. Hb, Bicarbonate, proteins, phosphate)
- combine with/release H+
2) Ventilation
- rapid
3) Renal
- direct via excretion/reabsorption of H+
- indirectly by changing amount of of HCO3- buffer reabsorbed/excreted
118
How does acidosis lead to hyperkalaemia?
H+ ions displace intracellular K+ (K+ efflux)
119
Alkalosis leads to (hyper/hypokalaemia)
Hypokalaemia (K+ influx in response to H+ efflux)
120
How does hyper/hypokalemia change the excitability of neurons?
hyper/hypoK+ → ↑/↓ cellular K+
→ depolarise/hyperpolarise
→ ↑/↓ RMP
→ >/< excitable
121
What is the Henderson-Hasselbach Equation?
pH= 6.1 + (log[HCO3-] / (0.03 x PCO2))
122
What are 3 causes of respiratory acidosis?
1) COPD
2) ↑ Airway resistance (eg. asthma)
3) Respiratory depression (eg. alcohol)
4) ↓ gas exchange (fibrosis, pneumonia, muscular dystrophy)
123
In respiratory acidosis:
CO2 ____
H+ _____
HCO3 ____
CO2 ↑ → H+↑ HCO3-↑
124
Compensatory mechanism(s) for respiratory acidosis?
Renal: ↑HCO3- reabsorption + ↑H+ secretion (DCT)
(48-72 hrs)
125
What are 2 causes of respiratory alkalosis?
1) Clinical/iatrogenic: Artificial ventilation
2) Physiological: Severe anxiety → hysterical hyperventilation
126
Compensatory mechanism(s) for respiratory alkalosis?
Renal: ↑HCO3- excertion+ ↑H+ reabsorption (DCT)
(48-72 hrs)
127
In respiratory alkalosis:
CO2 ____
H+ _____
HCO3 ____
CO2 ↓ → H+↓ HCO3-↓
128
What are 3 causes of metabolic acidosis?
1) Dietary: Aspirin, low CHO Atkins diet
2) Metabolic: Lactic (exertion), Ketoacidosis (DM)
3) Loss of HCO3- (eg. diarrhoea)
129
In metabolic acidosis:
CO2 ____
H+ _____
HCO3 ____
CO2 ↑
H+ ↑
HCO3 ↓
130
Compensatory mechanism(s) for metabolic acidosis?
Respiratory: ↓CO2 by hyperventilation (immediate)
Renal: ↑HCO3- reabsorption + ↑H+ secretion (DCT)
(48-72 hrs)
131
What are 2 causes of metabolic alkalosis?
1) Excessive vomiting of stomach contents
2) Excessive HCO3- (eg. antacids)
132
In metabolic alkalosis:
CO2 ____
H+ _____
HCO3 ____
CO2 ↓
H+ ↓
HCO3 ↑
133
Compensatory mechanism(s) for metabolic alkalosis?
Respiratory: ↑CO2 by hypoventilation (immediate, stops at PO2<60mmHg)
Renal: ↑HCO3- excretion + ↑H+ reabsorption (DCT)
(48-72 hrs)
134
How does the kidney compensate for acidosis?
H+ secretion:
a) H+ secretion → bound to HPO42- buffer → excreted in urine
b) H+ bound to amino acids to form NH4+ → excreted in urine
c) directly dissolved in urine
HCO3- reabsorption:
a) Apical Na/H exchanger → H+ efflux
b) H+ + filtered HCO3- → CO2 (diffuses into cell)
c) CO2 + H2O → HCO3- + H+ (returns to form +ve feedback a-c)
d) Glutamine → NH4+ + HCO3-
e) Apical NH4+/Na+ exchanger → Na+ influx
f) Basolateral Na+/HCO3- transporter →
→ HCO3- added to ECF buffer
135
What type of renal cells excrete H+ and reabsorb HCO3- in acidosis?
Type A intercalated cells in the collecting duct
136
How do Type A intercalated cells compensate for acid/base disorders?
↑H+ excretion and ↑HCO3- reabsorption in response to acidosis
1) ↑HCO3- reabsorption via basolateral HCO3-/Cl- antiport
2) ↑H+ secretion via apical H+/K+ antiport
137
What type of renal cells reabsorb H+ and secrete HCO3- in alkalosis?
Type B intercalated cells in the collecting duct
138
How do Type B intercalated cells compensate for acid/base disorders?
↑HCO3- excretion and ↑H+ reabsorption in response to alkalosis
1) ↑HCO3- excretion by apical HCO3-/Cl- antiport
2) ↑H+ reabsorption via Basolateral H+ATPase
139
What does an increased anion gap indicate?
Metabolic acidosis
↑metabolic acids eg. lactic/ketoacidosis
140
What does a low anion gap indicate?
1) ↓ unmeasured anions (albumin)
2) ↑ unmeasured cations (hyperK+/hyperCa2+/HyperMg2+, lithium intoxication, multiple myeloma)
141
How is anion gap calculated?
(Na+ + K+) - (Cl- + HCO3-)
142
What is the normal range of an anion gap?
14-18mM/L
143
The kidneys play a critical role in Ca2+ reabsorption through what vitamin?
Vitamin D in response to parathyroid hormones
144
For a px with acute respiratory acidosis, how do you calculate the expected HCO3- concentration?
1 for 10 (above pCO2>40mmHg)
24 + (pCO2-40)/10
eg. pCO2=60mmHg → expected HCO3-=26mmol/L
145
For a px with chronic respiratory acidosis, how do you calculate the expected HCO3- concentration?
4 for 10 (above pCO2>40mmHg)
24 + 4(pCO2-40)/10
eg. pCO2=60mmHg → expected HCO3-=32mmol/L
146
For a px with acute respiratory alkalosis, how do you calculate the expected HCO3- concentration?
2 for 10 (above pCO2<40mmHg)
24 - 2(40-pCO2)/10
eg. pCO2=30mmHg → expected HCO3-=22mmol/L
147
For a px with chronic respiratory alkalosis, how do you calculate the expected HCO3- concentration?
5 for 10 (above pCO2<40mmHg)
24 - 5(40-pCO2)/10
eg. pCO2=30mmHg → expected HCO3-=19mmol/L
148
For a px with metabolic acidosis, how do you calculate the expected pCO2?
1.5 + 8
1.5 x [HCO3-] + 8
eg. [HCO3-] = 18mmol → expected pCO2= 35mmHg
149
For a px with metabolic alkalosis, how do you calculate the expected pCO2?
7 + 20
0.7 x [HCO3-] + 20
eg. [HCO3-] = 36mmol → expected pCO2= 45mmHg
