Renal Physiology and Acid-base Balance/Disorders Flashcards
1
Q
What are the principle routes of H+ excretion?
A
Lungs as CO2 and H2O
Kidneys
2
Q
What is H+ excreted as in the lungs?
A
CO2 and H2O
3
Q
What is the initial [H+] pf glomerular filtrate?
A
40nmol/L
pH 7.4
4
Q
In what forms is H+ found in urine?
A
- Free H+
- Attached to phosphate (Na2HPO3, NaH2PO4)
- Attached to ammonia (NH3, NH4+)
5
Q
Why is urine titrated to pH 7.4?
A
pH of blood
Biologically neutral
6
Q
Explain what a heavy meat diet would do to urine acid?
A
More H+ in urine
7
Q
Explain what a vegetarian diet would do to urine acid?
A
Less H+
8
Q
What is the most important vehicle for H+ excretion?
A
Ammonia NH3
NH3 + H+ –> NH4 (Excreted)
9
Q
How is ammonia synthesised?
A
glutamine –> glutamate + ammonia (NH3)
glutaminase enzyme
10
Q
How is ammonia regulated?
A
glutaminase enzyme can be upregulated in the liver
glutamine –> glutamte + NH3
11
Q
In a patient with chronic kidney failure with a eGFR of 8 (normal is >60)
What does an elevated HCO3- indicate?
A
Metabolic acidosis
12
Q
In a patient with chronic kidney failure with a eGFR of 8 (normal is >60)
What does an decreased Ca2+ indicate?
A
due to decreased vit.d hydroxylation
vit d is required for absorbing calcium
check PTH levels
13
Q
In a patient with chronic kidney failure with a eGFR of 8 (normal is >60)
What does an elevated Phosphate indicate?
A
Bone resorption to maintain Ca2+
14
Q
In a patient with chronic kidney failure with a eGFR of 8 (normal is >60)
What does an decreased albumin indicate?
A
filtered from blood
proteinuria
Check albuminuria levels
15
Q
In a patient with chronic kidney failure with a eGFR of 8 (normal is >60)
What does an decreased HB indicate?
A
decreased EPO production
16
Q
In a patient with chronic kidney failure with a eGFR of 8 (normal is >60)
What does an elevated ALP indicate?
A
High-turnover bone disease
at risk of OP
17
Q
In a patient with chronic kidney failure with a eGFR of 8 (normal is >60)
What does an elevated K+ indicate?
A
hyperkalaemia
altered K+ distribution
Ability to excrete potassium decreases as GFR falls
18
Q
In a patient with chronic kidney failure with a eGFR of 8 (normal is >60)
What does an elevated Cl- indicate?
A
dehydration
high salt intake
Addison’s disease (adrenal insufficiency, no aldosterone released)
19
Q
List the body compartments and the % they represent
A
Total body water 60%
IC = 40%
EC = 20%
20
Q
On the arterial side, which pressure is higher and which is lower?
A
High hydrostatic pressure (IC to EC)
Low oncotic pressure (EC to IC)
21
Q
What is hydrostatic pressure?
A
IC to EC
22
Q
What is oncotic pressure?
A
EC to IC
23
Q
On the venous side which pressure is higher and which is lower?
A
Low hydrostatic pressure (EC to IC)
High oncotic pressure (IC to EC)
24
Q
What is the most common ECF cation?
A
Na+
25
What is the most common ECF anion?
Cl-
26
What is the most common EICF anion?
PO43-
27
What is the most common ECF cation?
K+
28
What is the mmol/L of ions IC and EC?
152mmol/L in both compartments
Therefore iso-osmolar
29
How much CO does the kidneys receive?
20%
30
Where do the kidneys lie relative to vertebrae?
T12-L3
31
What is the kidney's lymphatic drainage?
Para-aortic
32
What is normal GFR
approx 100mL/min
| 144L/day
33
What increases the SA for absorption on the PCT?
Epithelial cells with microvilli
34
How much NaCl is reabsorbed by the PCT?
approx. 70%
| Active transport
35
Where is glucose and AA reabsorbed?
PCT
Nearly 100%
Active trasport
36
What concentration can the interstitial medulla reach?
1,200mOsm/kg
4x the rest of the body
in order to move water out of the renal tubule, the concentration of the surrounding interstitium must be higher than within the tubule
37
What maintains the concentration gradient in the medulla ?
Countercurrent exchange
38
What an the thick ascending limb transport?
Impermeable to water
Actively transports Na+ K+ and Cl-
39
What can the thin descending limb transport?
Salt and water
40
How does the vasa recta not wash away the gradient?
Countercurrent exchange
41
What does the hyperosmolar medulla depend on?
Na+ reabsorption and urea trapping
42
What concentration can the interstitial medulla reach? And what causes this?
Approx. 1,200mOsm/kg
- half due to extrusion of sodium (3Na+/2K+-ATPase)
- half due to urea accumulation (urea trapping)
43
What's the role of ADH in urine concentration?
ADH activates aquaporins in the CD to allow reabsorption of water
44
What does ANP do?
```
Secreted in response to increased plasma volume
- afferent dilation
- efferent constriction
= increased GFR
= increase Na+ excretion and water
```
*inhibits aldosterone
45
Where is adenosine produced? And what effect does it have?
Adenosine is produced by the macula densa in response to increased tubular flow, it causes afferent arteriolar constriction to maintain GFR
46
Where is renin produced?
Renin is produced by the macula densa in response to decreased tubular flow, it triggers the RAAS system where AngII causes systemic vasoconstriction and aldosterone secretion by adrenal cortex to reabsorb Na+ (via ENaC) and water).
47
How is GFR maintained during increase or decrease in tubular flow?
Increased tubular flow
- JG apparatus secreted adenosine
- afferent arteriolar vasoconstriction
Decreased tubular flow
- JG apparatus secretes renin
- RAAS
- Ang II = systemic vasoconstriction
- Aldosterone = Na+ (ENaC) and H2O reabsorption
48
Define oligouria
Decreased urine output
49
Within the intravascular space, what is the main determinant of oncotic pressure?
Plasma proteins
50
What drives hydrostatic pressure?
Heart pumping and vessels constricting
51
What is the normal healthy omsolality ?
approx. 300mOsm/kg
52
What are the compartments of water?
IC
EC
-IV
-IT
53
What happens to omsolality when water is added into ECF?
Nothing. water distributes evenly across 3 compartments due to osmosis
54
What happens to omsolality when NaCl is added into ECF?
Particles and volumes in EC space increase
Add NaCl to plasma
ITS ALWAYS WATER THAT MOVES
there will be increased omsolality in plasma
water will be driven out of cells
55
What happens to omsolality when 1L water and 300mM NaCl is added into ECF?
300mM is the same osmolality as normal body
therefore, increase particles and volume in the EC space
nothing moves into the IC space
56
In health, what does ECF composition depend ont?
- salt intake - depends on hunger and food availability
- water intake - depends on thirst and water availability
- salt and water losses - sweat and GI
57
What are the structure of mesangial cells?
Phagocytic
| Secrete amorphous BM-like material known as mesangial matrix
58
What type of collagen is the glomerular filtration barrier made of?
Collage type IV
59
How big is the selective barrier of glomerular filtration sieve?
approx. 6.5nm
60
Where does the majority of reabsorption in the kidney take place?
PCT
61
What is the main driver os reabsorption?
Na+/K+-ATPase
| on basolateral surface (aka with the IT space NOT LUMEN)
62
Which part of the nephron is important in K+ and H+ excretion
DCT
63
Where are ENaC found?
DCT
64
Describe H+ excretion in the kidneys
1. 3Na+/2K+-ATPase on the basolateral surface creaters concentration gradient
2. if ENaC is present, Na+ moves into cell
3. Tubular lumen becomes negative
4. K+ moves out of the cells into the lumen
5. H+ can also be driven out of the lumen in this way
65
What channel is distinctively found in the thick ascending loop of Henle?
NKCC
Na+-K+-2CL
66
Describe ion movement in the thick ascending loop of Henle
1. Na+ concentration gradient created by 3Na+/2K+-ATPase
2. Na+ moves from tubule into the endothelial cell via NKCC - K+ moves with it creating an excess of K+ within the cell
3. K+ is actively pumped back out into the tubular lumen creating a charge within the tubular lumen
4. This allows Mg2+ and Ca2+ to squeeze through cells and reabsorbed
67
What is the functions of
PCT
DCT
LoH/CD
1. PCT
- Most NaCl and H2O reabsorption - 70%
- 100% AA and glucose reabsorption
- Some excretion of acid
2. DCT
- Fine tuning of NaCl and H2O
- Excretion of H+ and K+ (via Na/K-ATPase--ENaC system)
3. LoH and CD
- Altering overall concentration of urine via AQs
68
what mechanism concentrates urine?
Countercurrent exchange multiplier
69
What is the max urine osmolality
1200mOsm/kg
70
What two mechanisms trigger when blood volume and pressure decrease?
1. RAAS via juxtaglomerular apparatus macula denasa
2. SNS via baroreceptors
- causes vasoconstriction of afferent arteriole to reduce amount of blood filtered
71
How does the body normally respond to hyperkalaemic?
Release of aldosterone from the adrenal gland
1. Na+ concentration driven by movement of Na+ by Na/K-ATPase
2. ENaC drives Na into cell then into interstitla space
3. Tubular lumen becomes negative
4. K+ moves out of the cell into the tubular lumen to be excreted
(H+ can also be excreted in this manner)
72
Can H+ flow freely in body compartments
Yes, it all body compartments
73
How much H+ do we injest per day?
70mM
74
How much H+ do we produced per day from cellular respiration?
15,000mM
75
What is the function of HCO3-?
Buffering H+
76
What is a volatile acid
Creates gas
| e.g. carbonic acid
77
Where is HCO3- synthesised?
Kidney
| PCT also rapidly reabsorbs HCO3- for every 1H+ excreted as NH4+
78
Where in the kidney is EPO secreted from?
| And what is the function of EPO
Interstitial cells from the base of the loop of Henle
- kidneys are very good at detecting tissue hypoxia via countercurrent O2 exchange
EPO = erythropoietin
- regulated erythropoiesis
79
What is a hypotonic solution?
| Give examples
THINK HYPOTONIC MEANS WANTS TO GET RID OF WATER
Solution that has less solute and more water than other solution
High water concentration
- drive water into cells
- cells can burst
E.g.:
- 0.25% NaCl
- 2.5% Dextrose
80
What is a isotonic solution
Concentration inside the cell = concentration in IV
- cell at equilibrium
E.g.:
- 0.9% Saline NaCl (normal saline)
- - Lactated Ringer's Solution
81
What is a hypertonic solution
THIS: HYPERTONIC MEANS WANTS WATER
Greater concentration of solutes outside the cell that inside the cell
- can cause cells to shrink
- higher osmolality outside the cell
- water leaves cell
E.g.:
- 5% dextrose in 0.9% NaCl
- 5% dextrose in Lactated Ringers
- 5% dextrose in 0.45% NaCl
82
What is the unit measure of kidney function?
Total GFR
83
Define clearance
* amount of fluid that has been completely cleared
Calculated by:
Clearance = [particles]urine / [particles]plasma
84
What is the gold standard substance to measure GFR?
| And why
Inulin
- freely filtered by the glomerulus and is neither re-absorbed or secreted by the tubule
- too expensive and cumbersome for clinical practice
- used in animal research and in kidney donation protocols
85
Why is creatinine clearance a good measure of GFR?
What other substance is like this?
1. produced by body at a constant rate
2. filtered freely at the glomerulus
3. not reabsorbed or secreted
Other substance: Cystatin C
86
What is creatinine?
- Normal product of muscle metabolism
- Daily production is constant
- [Creatinine]plasma dependent on muscle mass, kidney function and protein intake
- Incompletely filtered but some tubular secretion (these cancel each other out)
87
What is an endogenous good estimate of GFR?
CrCl
| Creatinine clearance
88
What problems are there with measuring creatinine in determining kidney function?
[Cr]Serum
- inverse relationship leads to:
1. slow recognition of loss of the first 70% of kidney function
2. Surprise sudden rise in creatinine
__
Over estimation in women
Overestimation in elderly
Overestimation in lower mass groups (e.g. amputees)
89
How were the problems involving serum creatinine measurements overcome?
MDRD 4-variable formula for estimated (e)GFR
1. Serum creatinine
2. Age
3. Female
4. Black ethnicity
Unit: mL/min/1.73m^2
90
When is eGFR not acurate
- >60mL/min
- <18yo
- not accurate estimate of kidney function in steady state
91
What variables are taken into consideration with the MDRD formula for eGFR calculation?
1. Serum creatinine
2. Age
3. Female
4. Black ethnicity
92
What is "normal" eGFR?
approx. 100mL/min/1.73m^2
93
What eGFR suggests reduced kidney function
<60mL/min/1.73m^2
94
What does proteinuria clinically suggest?
Glomerular disease
*+/- blood
95
How would you determine concentration of protein in urine?
protein:creatinine ratio
96
How would you determine the level of an electrolyte being filtered?
Fractional excretion
e.g.
[Na]urine x Volume of urine = mmol Na excreted
[Na]urine x eGFR = mmol Na excreted
97
What biochemical readers indicate the kidneys are NOT working properly?
- Low eGFR <60mL/min
- Raised [Creatinine]serum when eGFR >60mL/min
+ examine urine for proteinuria
98
Describe how would you define kidney injury/disease
- Reduced eGFR
- proteinuria
- +/- blood (haematouria)
- once above defined, combine with Hx, examination, and investigation to identify aetiology
99
What pathology does oliguria indicate?
oliguria = decreased urine output
- warning for impending acute tubular necrosis
100
What is acute tubular necrosis?
Acute tubular necrosis (ATN) is a medical condition involving the death of tubular epithelial cells that form the renal tubules of the kidneys.
ATN presents with acute kidney injury (AKI) and is one of the most common causes of AKI.
Common causes of ATN include low blood pressure and use of nephrotoxic drugs.
101
Define necrosis
Death of cells due to any insult
102
Give an example of acute kidney injury (AKI)
Acute tubular necrosis due to reduced low BP or nephrotoxic drugs etc.
103
Aetiology of chronic kidney disease (CKD)
1. Renovscular disease
- atherosclerosis
- hypertension
2. Glomerular disease
- glomerulonephritis
3. Tubulo-intestitial disease
- congenital autosomal polycystic kidney disease
- chronic nephrotoxic ingestion
- autoimmune
4. Obstructive uropathy
- bladder outflow: enlarged prostate, urethral stricture
- bladder cancer/cervical cancaer
5. Following AKI
104
What 3 categories can AKI/CKD be classified as?
- Pre-renal
- Obstructive
- Post-renal
105
What CDK classification is established renal failure?
```
Stage 5 (final stage)
eGFR <15 or on dialysis
```
106
What are the main evidences of kidney damage?
Biochemically: proteinuria (persistant)
Or
Abnormalities such as polycystic kidney
107
When is eGFR not accurate?
eGFR>60
108
What is the most common modality used in renal imaging?
Ultrasound
109
Upon ultrasound, what size of kidney is considered normal and abnormal?
- >10cm is normal
| - <9cm is abnormal and indicative of chronic disease
110
Comment on ultrasound echobrightness
- Normal: liver is more echobright than kidney
| - Abnormal: kidney is more echobright than liver
111
Define hydronephrosis
Swelling of kidney due to buildup of urine
| - occurs when urine cannot drain out from the kidney to the bladder due to blockage or obstruction
112
Give an example of an intrinsic and extrinsic blockage that can lead to hydronephrosis
- intrinsic: kidney stone
| - extrinsic: extrinsic compression of ureter (e.g. tumour)
113
What contrast is used in CT?
iodine
* its nephrotoxic therefore weigh up risks vs benefits
114
What contrast is used in MRI
Gadolinium
115
When should you avoid using contrast imaging with kidneys?
eGFR <30
| Stage 4/5 CKD
116
What type of renal stones can form?
Calcium
Oxalase
Urate
Cysteine
117
Define kidney stones
A solid concretion of crystal aggregates forms within urinary space
- formed from the combination of excreted/secreted ions within glomerular filtrate
12% men and 5% women by age 70
118
Classify stones by location and composition
- Location
1. Kidney: nephrolithiasis
2. Ureter: ureterolithiasis
3. Bladder: cystolithiasis
- Compsition
1. Calcium-phosphate/Calcium-oxalate
2. Urate/cysteine etc..
119
What are the risk factors for kidney stones?
1. Genetic
- Male - 50% chance
- Family history: RR 2.5
2. Environmental
- BMI >27 (obese) RR 2.0
- Immobile or sedentary (seated too much)
- Dehydration
- UTI
- Rise in obesity and metabolic syndrome have caused an increase in uric acid stones
* Protected:
- Vegetarians RR 0.5
- High fruit diet RR 0.6
- High fibre diet RR 0.6
120
What environmental factors protect against kidney stones?
* Protected:
- Vegetarians RR 0.5
- High fruit diet RR 0.6
- High fibre diet RR 0.6
121
Kidney stone compositions
1. Calcium containing - 80%
- Calcium oxalate
- Calcium phosphate
2. Struvite stones - 5-10%
- Magnesium
- Ammonium
- Phosphate
* bound together, tends to happen with increased ammonia production e.g. persistent UTI with bacteria having urease enzyme (urea --> ammonia = stones)
3. Uric acid - 5-10%
- Gout (inflammatory arthritis)
4. Cysteine - 1-2%
5. Mixed
122
What MAIN components are used to maintain acid-base balance?
1. Buffering - short term process to control H+
2. Ventilation - Control of CO2
3. Renal regulation of HCO3- and H+ reabsorption and secretion
123
What is the normal pH and [H+] of blood?
pH 7.4
| 40nmoles/L
124
What blood biochemistry changes at the expense of buffering H+?
[HCO3-]
| pCO2
125
Define fixed acid
acid produced in body from sources other than CO2
126
Define volatile acid
acid produced in the body from CO2
127
How are CO2 and HCO3- regulated>
CO2 by respiration in the lungs
| HCO3- by kidneys
128
Are dietary acids and acids produced by anaerobic respiration fixed or volatile acids?
Fixed
| they cannot be converted into CO2
129
How do the kidneys regulate acid-base balance
2 mechanisms:
1. Reabsorb the freely filtered HCO3-
2. Secrete/titrate "fixed" acid
- titrate non-HCO3- buffer in urine primarily phosphate
- secretion of ammonium (NH4) into urine
130
Where is HCO3- normally reabsorbed ?
PCT
normally ALL is reabsorbed
>4,000mmol/day
131
What is the name of the disorder that results in an inability to reabsorb filtered HCO3-?
Renal tubular acidosis
132
Mechanism for re-absorbing HCO3-
1. Tubular microvilli packed with carbonic anhydrase
2. Generates H2O and CO2 from HCO3- in filtrate
3. H2O and CO2 diffuse into cell where they care converted back into HCO3- and H+ via carbonic anhydrase
4. HCO3- is transported through the basolateral surface of the cell into the interstitium
5. H+ is transported across the tubular cell membrane back into the tubule
133
What buffers can be used to excrete fixed acids?
two bases can be used
- Phosphate PO4: depends on delivery of filtered buffer and cannot be upregulated
- Ammonia NH4+: can be upregulated by liver in acidosis
NEW HCO3- GENERATED
134
What is the name of the condition where you cannot excrete fixed H+ in the DCT?
Distal tubular acidosis
135
What is the difference between
Distal tubular acidosis
and
Proximal tubular acidosis
Proximal tubular acidosis: inability to reabsorb HCO3- in PCT
Distal tubular acidosis: inability to excrete fixed H+ in DCT
136
How can ammonium buffer be upregulated?
- involves the liver, people with liver failure can become acidotic
- via glutamine metabolism
- process regulated and can be up regulated
glutamine --> glutamate + ammonia (NH3)
NH3 binds to H+ in the urine to be excreted at NH4+ (ammonium)
and NEW HCO3- is created in the cells and reabsorbed
137
What is the difference between acidosis and acidaemia
Acidosis: tendency to acid-base disturbance, but with normal [H+]; low HCO3- and low pCO2
Acidaemia: have high [H+]
*most patients will be acidotic
138
What is the biochemical Dx of metabolic acidosis?
Explain.
- increased [H+]
- normal/decreased pCO2
- decreased HCO3-
The body will compensate for increase [H+] by consuming a HCO3- (it'll decrease) and then compensate by driving off CO2 (pCO2 decreases)
Consequence of driving off too much CO2 = respiratory alkalosis
*respiratory compensation
139
What is the biochemical Dx of respiratory acidosis?
Explain.
- increased [H+]
- normal/increased pCO2: patient cannot ventilate CO2
- normal/increased HCO3-: HCO3- is retained by kidneys because lungs aren't ventilating
*renal compensation
140
List main causes of metabolic acidosis
Vomiting
Hyperventination
Drugs
141
What is the name given to hyperventilation to drive off CO2 during metablic acidosis?
Kassmaul's breathing
142
What is the equation for anion gap?
[Na+] - ([Cl- + [HCO3-]) = 6-12mmol/L
unmeasured cations - unmeasured anions
*in ECF
143
What does the anion gap tell you?
Reflects the presence of unmeasured anions
144
What is the purpose of calculating anion gap?
Identifying the cause of metabolic acidosis - esp. lactic acidosis, ingestion of food, poison
145
What happens in lactic acidosis
production of lactic acid (metabolism) > renal excretion of H+
Acidosis usually results from hypo-perfusion and reduced hepatic clearance of lactate
146
In what situations would you get metabolic acidosis with a raised anion gap?
when there is an unmeasured anion organic acid present
| e.g. lactate, keto-acids, or ingestions (e.g. methanol)
147
In what situations would you get metabolic acidosis with a normal anion gap?
In most metabolic acidosis, the acidosis is due to loss of HCO3- and therefore the anion gap does NOT increase
e.g. diarrhoea, renal tubular acidosis, chronic kidney failure
148
What is the physiological anion that is not measured in the anion gap formula?
Albumin
149
Give 2 examples of common acidosis
- Lactic acidosis in shock
| - Diabetic ketoacidosis (DKA)
150
How would you Tx acidosis/alkalosis
Treat cause!
151
Which values of [H+] are incompatible with life?
>120nmol/L
| <20nmol/L
152
Name 2 sulphur containing AAs
What happens to the sulfur?
what kind of diet is this?
Whats the "risk"?
Cysteine and methinine
Converted into sulphuric acid H2SO4
Protein (acid) diet
Risk of acidosis
153
What kind of diet give alkaline load?
| What kind of salts does it contains and what is this converted to?
Vegetarian diet
Contains salts of carboxylic acids (sodium citrate)
- these care converted to sodium carbonate (Na2CO3) an alkali
