Sugar 1 Flashcards

1
Q

What is a regular Renal blood flow?

What is normal renal plasma flow?

A

Blood: 1L/min to 1250ml/min
Plasma: 700ml/min

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2
Q

What is a regular urine flow?

A

approx 1 ml/min

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3
Q

Describe the vessels involved passage of blood through the kidney

A
Renal Artery >
Interlobar Artery >
Arcuate artery >
Interlobular artery >
Afferent arteriole >
(Nephron:)Glomerular capillary > 
Efferent Arteriole >
Peritubular capillary >
vein
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4
Q

Which blood vessel passes through the glomerulus?

A

Glomerular capillary, involved in Glomerular Filtration into Bowman’s space

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5
Q

Which blood vessel runs alongside tubules?

A

Peritubular capillary - involved in tubular secretion and reabsorption

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6
Q

What is the importance of the Peritubular capillary?

A

Many tubular processes are of secretion and reabsorption are active, requiring energy and oxygen. Therefore blood supply is v important.

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7
Q

What is the surface area for glomerular filtration?

A

approx 1m^2

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8
Q

Which part of the nephron (tubule) is responsible for secretion and reabsorption?

A

Distal part/tubule

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9
Q

Name the 4 layers of the filtration barrier

A
[Urinary Space]
Podocyte
Foot processes
BM
Capillary endothelium
[Capillary]
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10
Q

Name 3 podocyte and slit diaphragm proteins

A

Nephrin
Podocin
CD2AP

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11
Q

What determines the rate of crossing the filtration barrier?

A
  • Pressure (difference)
  • Size of molecule (larger molecules increasingly restricted)
  • Charge of the molecule
  • Rate of blood flow
  • Binding to plasma proteins e.g. calcium, hormones such as thyroxine
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12
Q

What is the fixed charge if the glomerular BM?

A

Fixed negative charge that repels negatively charged anions

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13
Q

Name small molecules and ions that can pass freely through the filtration barrier

A

Small molecules and ions up to 10kDa can pass freely e.g. glucose, uric acid, potassium, creatinine

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14
Q

Why can albumin protein not pass through a normal filtration barrier

A
  • Molecular weight of 66kDa (>10)

- Negatively charged so repelled by glomerular BM

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15
Q

What is Tamm Horsfall (uromodulin) protein?

A

Protein in urine produced by tubules. Found in ordinary urine and exception to filtered fluid being ‘protein-free’

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16
Q

What is the hydrostatic pressure difference between the Glomerular capillary (GC) and Bowman’s space (BS)?

A

P(GC) = 45mmHg
P(BS) = 10mmHg
therefore fluid moves into BS
Hydrostatic pressure constant along length of capillary

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17
Q

What is the osmotic pressure difference between GC and BS?

A

OP(GC) = 25mmHg and rising
OP(BS) = zero
osmotic pressure rises along the length of capillary

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18
Q

Define Glomerular Filtration Rate (GFR)

A

Filtration volume per unit time (mins)

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19
Q

What is the equation for GFR?

A

GFR = Kf (pGC - pBS) - (opGC - opBS)

Kf is filtration coefficient

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20
Q

Can you alter net ultrafiltration pressure?

A

Cannot alter permeability or oncotic pressure.

Potential to alter hydrostatic pressure or SA

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21
Q

How to decrease GFR

A

Constrict afferent arteriole
Dilate efferent arteriole
Also if loose nephrons

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22
Q

How to increase GFR

A

Constrict efferent arteriole

Dilate afferent arteriole

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23
Q

What is the systemic mean arterial pressure range in normal kidney

A

90-200mmHg

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24
Q

Are kidneys auto-regulated?

A

Yes and occurs in denervated or isolated perfused kidneys (not dependent on nerve supply or blood-borne substances)

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25
Q

Describe process of auto-regulation in kidney

A

Pressure within afferent arteriole rises >
stretches vessel wall >
triggers contraction of smooth muscle >
arteriolar constriction [Intrinsic property of vascular smooth muscle]
(reverse happens when systemic arterial pressure falls)

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26
Q

Purpose of autoregulation

A

Prevents an increase in systemic arterial pressure from reaching the capillaries

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27
Q

Describe Tubuloglomerular feedback

A

GFR of individual nephron regulated by the rate at which filtered fluid reaches the distal tubule
Cells of macula densa (distal tubule) detect NaCl arrival
Macular densa cells release prostaglandins in response to reduced NaCl delivery
This acts on granular cells, triggering renin release, activating the renin-angiotensin system.

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28
Q

How is GFR measured?

A

Measure excretion of a marker substance that is freely filtered (same conc in blood and tubular fluid), not absorbed in tubules and not metabolised.
Amount (not concentration) excreted per min = Amount filtered per min
Amount of marker (M) in fluid = concentration in fluid x volume of fluid

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29
Q

What is a normal GFR?

A

125ml/min

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30
Q

Equation for GFR

A

GFR = Um x urine flow rate/Pm
Um is concentration of M in urine
Pm is concentration of M in plasma

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31
Q

What is used clinically to estimate GFR?

A

Creatinine (muscle metabolite)
Serum creatinine varies with muscle mass
Its freely filtered at glomerulus

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32
Q

What is filtration fraction

A

Filtraction fraction = GFR/renal plasma flow

e.g.120/600=20%

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33
Q

What are standard Renal blood flow and Renal plasma flow

A

Renal blood flow = 1000ml/min
Penal Plasma flow = 600ml/min
(about 40% of blood is cells, rest is plasma)

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34
Q

Define the concept or renal clearance

A

Volume of plasma from which a substance is completely removed by the kidney per unit time (usually a minute).
Marker substances are freely filtered at glomerulus and all will end up in urine.

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35
Q

Equation for renal clearance

A

Clearance (ml/min) = urine concentration x urine volume/plasma concentration

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36
Q

What is renal clearance of glucose in normal kidney?

A

0ml/min

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37
Q

What would be an approx value of renal clearance for Urea and PAH (para-aminohippurate)

A

Urea 65ml/min

PAH 625ml/min

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38
Q

What is the equation for pH

A

-log[H+]

low ph = high acidity

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39
Q

Define Acidosis

A

Disorder tending to make blood more acidic than normal

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40
Q

Define Alkalosis

A

Disorder tending to make blood more alkaline than normal

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41
Q

Define Acidemia

A

Low blood pH

42
Q

Define Alkalemia

A

High blood pH

43
Q

Define Standard bicarbonate

A
  • Bicarbonate concentration standardised to pCO2 of 5.3kPa and temp of 37
  • Affected by both respiratory and metabolic components. However, measure of metabolic component of acid-base disturbance.
44
Q

Define Base Excess

A

Quantity of acid required to return pH to normal under standard conditions.
In acidosis, base excess is negative - in this case it’s also called base deficit.

45
Q

How can base excess value be used

A

To calculate the bicarbonate dose needed to correct acidosis:
0.3 x Weight (kg) x BE (mEq/L)

46
Q

Define Standard Base Excess

A

Base excess corrected to Haemoglobin of 50g/L

47
Q

What is measured in Arterial Blood Gas (ABG)

A

pH, pO2, pCO2, Std HCO3-, Std Base excess, may include others (lactate, Na+, K+)

48
Q

What are the two methods interpreting acid-base status?

A
  • Henderson-Hasselbalch Equation

- Stewart’s Theory (strong ion difference)

49
Q

What is Henderson-Hasselbalch Equation

A

pH=6.1+ log([HCO3-]/0.03xpCO2)

50
Q

Carbonic Acid (H2CO3) can make CO2+H2O or H+ + HCO3-. What is normally removed from the body and where?

A

CO2 can be excreted in lungs
H+ excreted in kidneys
(HCO3- is recycled)

51
Q

According to Stewart’s strong ion difference, what are pH and HCO3- governed by?

A

-pCO2
-Concentration of weak acids (ATOT)
ATOT=Albumin+Pi+Pr
-Strong ion difference (SID) = Na+ + K+ + Ca2+ - Cl- - other strong anions (lactactate, ketoacids)

52
Q

Causes of metabolic acidosis

A
  • Failure of H+ excretion (Renal failure, hypoaldosteronism, type 1 renal tubular acidosis)
  • Excess H+ load: Lactic acidosis, Ketoacidosis, ingestion of acids (salicylate, ethylene glycol)
  • HCO3- loss (diarrhoea, type 2 renal tubular acidosis)
53
Q

How does the body compensate for metabolic acidosis

A

Hyperventilation to increase CO2 excretion

54
Q

What is the Anion Gap

What is cause of wide and narrow gap?

A

Difference between measured anions and cations: [Na+]+[K+]-[Cl-]-[HCO3-]
Normal 10-16
Wide anion gap: Lactic acidosis, ketoacidosis, ingestion of acid, renal failure
Narrow anion gap (high chloride): GI HCO3- loss, renal tubular acidosis.

55
Q

Causes of metabolic alkalosis

A

Alkali ingestion
GI acid loss - vomiting
Renal acid loss - hyperaldosteronism (high aldosterone), hypokalaemia

56
Q

Compensatory Mechanism for metabolic alkalosis

A

Hypoventilation (limited by hypoxic drive)

Renal bicarbonate excretion

57
Q

Define respiratory acidosis

A

CO2 retention leading to increased carbonic acid dissociation

58
Q

Causes of respiratory acidosis

A

Any cause of renal failure

59
Q

Compensation by body for respiratory acidosis

A

Increased renal H+ excretion and bicarbonate retention (but only if chronic)

60
Q

Define respiratory alkalosis

A

CO2 depletion due to hyperventilation

61
Q

Causes of respiratory alkalosis

A

Type 1 respiratory failure, anxiety/panic

62
Q

Compensation by body for respiratory alkalosis

A

Increased renal bicarbonate loss (**long term however - if this is not present in patient, would show acute injury and this is similar for others)

63
Q

What does failure to reabosrb bicarbonate (in RCT type 2 renal tubular acidosis) cause in a patient

A

Acidosis, impaired growth

64
Q

What are 3 things in body detect fall in BP by body

A
  • Juxtaglomerular Apparatus (Kidney)
  • Baroreceptors (Aorta)
  • Atrial Stretch Receptors (Heart)
65
Q

What does Juxtaglomerular apparatus cells secrete?

A

Renin

66
Q

What does renin act on?

A

Cleaves Angiotensinogen to form Angiotensin I

67
Q

Where is Angiotensinogen produced?

A

Liver (along with other proteins)

68
Q

Where is Angiotensin-converting enzyme produced and what does it convert?

A

Angiotensin I to Angiotensin II

Made in the lungs/pulmonary and renal epithelium

69
Q

What stimulates the production of Renin?

A

Decrease in renal perfusion pressure via stretch receptors in vascular walls.
Released in response to stimulation of beta adrenergic receptors on cells of JGA

70
Q

What actions does angiotensin II have on body?

A

Overall increases water and salt retention as well as increases perfusion of JGA. This is done by:

  • Sympathetic activity
  • Tubular Na+ Cl- reabsorption, K+ excretion, H2O retention
  • ALDOSTERONE secretion (increases^) from adrenal gland/cortex
  • Arteriolar vasoconstriction (increase in BP)
  • ADH secretion by posterior pituitary gland - causes more water reabsorption by the collecting duct
71
Q

What is aldosterone?

A

Steroid hormone that raises BP overall
Produced in glomerulosa of adrenal cortex in adrenal gland
Essential for sodium conservation in the kidney (collecting ducts mainly), salivary glands, sweat glands, colon.

72
Q

What are the 3 layers of the adrenal cortex?

A
  • (Zona) Glomerulosa (Outermost layer and Salt: Aldosterone)
  • Fasciculata (Sugar: glucocorticoids that regulate glucose metabolism)
  • Reticularis (Sex: precursor androgens)
73
Q

What do Atrial Naturetic Peptides do?

A

act on renal collecting tubules to promote Na+ excretion (reduce BP)

74
Q

Where is the kidney anatomically located?

A

Retroperitoneal space
Right kidney slightly lower than left as pushed down by the liver
..

75
Q

What is the method by which urine passes through the ureter?

A

Peristalsis (vermification?)

Detrusor muscle is unconscious control

76
Q

What are the layers of kidney?

A

Capsule
Cortex
Medulla
Pelvis

77
Q

Which parts of body are lined by urothelium/transtitional epithelium?

A

Renal pelvis, Ureters, bladder, parts of urethra

78
Q

What are 3 general causes of Acute Kidney Injury?

A

Pre-renal (most common, caused by e.g. decompensated liver failure/heart failure, cellulitis (as caused by sepsis leading to vasodilation and low BP), D+V)
Renal
Post-Renal (relatively rare)

79
Q

How does decompensated liver failure/heart failure lead to AKI?

A

Liver failure -> no protein produced, oncotic pressure decreases and fluid leaks out of BVs
Heart -> Fluid leaks out of capillaries
Less pressure in afferent arteriole

80
Q

What is the Henderson-Hasselbach Equation

A

pH=pK’+log(HCO3-/CO2)
OR
pH=6.1+log(HCO3-/CO2*)

*alpha pCO2

81
Q

What s the equation representing the bicarbonate buffer?

A

CO2+H2O H2CO3 H+ + HCO3-

82
Q

What is the purpose of Hydrogen Ion secretion in the renal arm?

A
  • reabsorb HCO3- (4000 mEq/day)

- excrete daily acid load (50-100mEq/day)

83
Q

What two substances are required to excrete acid load?

A

Phosphate and Ammonium

urinary buffers

84
Q

What is minimum urine pH

A

4.5

85
Q

In tissue capillaries, what 5 layers make up the respiratory arm? What happens at each?

A
  • Cells - where CO2 produced
  • Interstitial fluid - dissolves co2
  • Capillary wall - co2 passes through
  • Plasma - some co2 remains dissolved
  • Erythrocytes - some dissolved co2 from plasma binds to Hb. Some remains dissolved. Some goes through bicarbonate buffer reaction
86
Q

In pulmonary capillaries, what layers/parts make up respiratory arm? What happens at each?

A
Erythrocytes - Dissolved CO2 is formed. HbCO2 goes to dissolved CO2 +Hb. H2CO3 goes to CO2 and H2O.
Plasma- dissolved CO2 passes though
Capillary Wall
Alveoli- becomes CO2
Atmosphere - expired CO2
87
Q

Between plasma and erythrocytes, what co-transporter is found that is involved in use of dissolved CO2?

A

HCO3-/Cl- co-transporter
In tissue capillaries, HCO3- moves into plasma and Cl- moves into erythrocytes.
Vice versa in pulmonary capillaries

88
Q

Bicarbonate reabsorption describe

A

H+ secretion by apical Na+/H+ antiporter
Carbonic anhydrase (brush border) - CO2
Carbonic anhydrase (cell) - HCO3-
Basolateral Na+/ 3HCO3- symporter
Result - HCO3- reabsorbed in proximal tubule (90%), pH falls from 7.4 to 6.7

Note that HCO3- is impermeable to apical membrane

89
Q

What is Titratable acidity

A

Quantity of base required to bring pH to 7.4.
NOT increased in response to acidosis.
(10-40 mEq H+ per day)

90
Q

What is the most common Urinary Phosphate Buffer? What is the equation?

A

Alkaline phosphate Buffer (HPO4^2-)

HPO42- + H+ -> H2PO4- (pKa 6.8)

91
Q

What does Glutamine produce/breakdown into in proximal tubule, for urinary ammonia buffer?

A

NH3
NH4+
alpha ketoglutarate

92
Q

What is the effect of acidosis on urinary ammonia buffer?

A

Uptake and enzymes increased (3 day max response).

Urinary ammonia buffer is generally an adaptive response to acid load (30-300 mEq/day)

93
Q

Name 3 weak acids

A

Urate
Creatinine
beta Hydroxybutyrate

94
Q

What are different movement of ammonia in urinary ammonia buffer?

A
  • Some pumped into lumen as NH4+, some diffuses as NH3
  • Reabsorbed in loop of Henle (counter-current multiplication)
  • Goes back into the collecting duct, where H+ is being pumped (tight segment)
  • NH3 diffusion/channels
  • Trapping of NH4+
95
Q

Which cells in body generate Erythropoietin (EPO)?

A

Peritibular cells in interstitial space of renal cortex (kidney)

96
Q

What does Erythropoietin stimulate and what are roles?

A

Stimulates bone marrow - promotes RBC maturation, receptors on early progenitor RBC.
Also inhibites apoptosis (survival facotr) allowing differentiation into RBC

97
Q

Conditions of high EPO

A

Anaemia, Altitude, Cardiopulmonary disorders

98
Q

Conditions of low EPO

A

Polycythaemia, Renal Failure

99
Q

What regulates EPO

A

Hypoxia-inducible factor (HIF)-2

100
Q

In vitamin D activation, What does Calcitriol act on?

A

Intestine (increases calcium and phosphate absorption)
Bone (increased bone resorption)
Kidney (increased calcium and phosphate reabsorption)
Parathyroid hormone (decreases parathyroid hormone which inhibits bone resorption)

101
Q

Which organs are involved in vitamin D activation?

A

Liver - produces 25-OH cholecalciferol

Kidney - Calcitriol)