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Kidney physiology Flashcards

1
Q

What is the glomerular filtration rate (GFR)?

A

how much filtrate is removed from blood each min and not how much blood passes through glomerulus per minute

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2
Q

How does glomerular filtrate differ from plasma?

A

Devoid of cellular elements like RBC

Essentially protein-free

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3
Q

How is glomerular fluid formed?

A

By passive ultrafiltration of plasma across the glomerular membrane, as described by Starling’s principle of capillary fluid filtration.

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4
Q

What drives the glomerular filtration process?

A

a net pressure difference across the glomerular membrane

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5
Q

How is the intrinsic control of GFR maintained?

A

Constriction of efferent arteriole (Bayliss Myogenic response)
Tubule-Glomerular feedback (TFG)

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6
Q

What is the extrinsic control of GFR?

A

renal sympathetic vasoconstrictor nerve activity

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7
Q

Which receptors mediate the parasympathetic nervous system in the bladder?

A

muscarinic receptors

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8
Q

Which pressures favour filtration in the nephron.

A

glomerular capillary pressure (~60mm Hg)

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9
Q

Which pressures in the nephron oppose filtration?

A

hydrostatic pressure in Bowman’s space

Osmotic force of plasma proteins

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10
Q

What is Bowman’s space?

A

space between arteriole bundle and epithelium of capsule

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11
Q

What types of cells are found coating the outer surface of capillaries?

A

podocytes

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12
Q

Which proteins are found within the filtration slits between podocytes?

A

nephrin

podocin

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13
Q

What do deficiency in nephrin and podocin cause?

A

nephrotic syndrome

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14
Q

How wide is a filtration slit? What molecule can therefore not pass?

A

4nm

albumin (as it is 4nm in width)

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15
Q

Why does proteinuria occur?

A

Damage to the filtration slits or damage to basement membrane

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16
Q

What are the 3 layers that the glomerular membrane consists of?

A

fenestrated capillary
basement membrane
filtration slits of podocytes

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17
Q

What is GFR an important clinical indicator of?

A

renal function

specifically nephron function

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18
Q

GFR is measure by:

A

creatine - which is filtered but not reabsorbed by the nephron

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19
Q

What is inulin?

A

An inert polysaccharide
Filters freely through the glomerular membrane
Not absorbed, secreted or metabolised

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20
Q

What are the main functions of the kidney?

A

Control volume and composition of ECF
Waste excretion
Acid-base balance
Endocrine organ (renin and EPO)

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21
Q

How many nephrons are there on average in each kidney?

A

1 million

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22
Q

What is the function of the Bowman’s capsule?

A

To filter large amounts of plasma

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23
Q

What the 2 main structural components of a nephron?

A

Bowman’s capsule+glomerulus

Renal tubule

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24
Q

What broad process occurs in the renal tubule?

A

Glomerular filtrate is converted to urine

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25
What is the volume of urine production that is considered to be renal failure?
< 5ml/day
26
In which direction does reabsorption occur?
tubular lumen -> peritubular plasma
27
What direction does secretion occur?
peritubular plasma -> tubular lumen
28
What does the basolateral membrane refer to?
The side of the epithelium cell layer facing/closest to the peritubular vessels
29
What does the luminal/apical membrane refer to?
The side of the epithelium cell layer facing/closest to the renal tubule lumen
30
What sits between the basolateral membrane and the peritubular vessels?
interstitial fluid
31
What is a symporter?
Type of secondary active co-transport channel where 2 ions move in the same direction
32
What is an anti porter?
Type of secondary active co-transport where 2 ions move in opposite directions
33
What type of nephrons have short Loop of Henlés? | What is the opposite type of nephron?
``` Cortical nephron (85% of total nephrons) - short LoH Juxtamedullary nephrons (15% of total nephrons) - long LoH ```
34
What structural features give PCT epithelium its ability to handle high levels of reabsorption?
``` highly metabolic numerous mitochondria (for active transport) extensive brush border (rapid exchange) ```
35
Where is the PCT located in the nephron?
directly adjacent to Bowman's capsule
36
What is the main function of the PCT?
reabsorption of <70% of the filtered load
37
By what processes does reabsorption occur in the PCT?
Transcellular transport of luminal and basolateral membranes (bidirectional) involves both passive and active transport
38
What is Fanconi's syndrome?
Defective reabsorptive mechanisms in the PCT
39
How is Fanconi's syndrome clinically identified?
presence of Glucose, AAs, Na+, K+, etc all found in urine
40
What are the main causes of Fanconi's syndrome?
inherited acquired e.g. malignancy medications e.g. sodium valproate
41
What are the 3 functional segments of the LoH?
thin descending thin ascending thick ascending
42
What are the structural features of the thin descending limb of the LoH?
thin epithelial cells no brush border few mitochondria low metabolic activity
43
What are the structural features of the thin/thick ascending limbs of the LoH?
thick epithelial walls lateral intercellular folding some microvilli many mitochondria
44
What is the broad function of the loop of Henlé?
Critical role in concentrating/diluting urine
45
Which limb of the loop of Henlé is impermeable to water?
Ascending | thin and thick
46
What proportion of fluid is reabsorbed in the descending limb of the LoH?
20% of the water
47
What occurs in the ascending LoH?
Active reabsorption of Na+
48
What is the overarching mechanism which facilitates reabsorption in the LoH?
countercurrent exchange
49
Which process do loop diuretics (e.g. furosemide) affect in the LoH?
Active Na+ reabsorption in the thick ascending limb | This means that ~20% of the Na+ is renally excreted
50
How is the medullary osmotic gradient at the nephron maintained?
LoH creates gradient in medullary interstitium (outer medulla) Collecting duct traverses medulla as water is reabsorbed (inner medulla)
51
How does the osmolality of the filtrate change as you travel towards the inner medulla?
It becomes more hyperosmotic | ~1200 mOsm/kg near bottom of LoH
52
Loop diuretics (e.g. furosemide) inhibit which transporter? Where does this occur?
Na+Cl-K+ symporter in the thick ascending limb in the Loop of Henlé
53
What maintains the counter current exchange gradient in the nephron?
Opposing direction of flow between vasa recta (blood capillaries) and filtrate flow osmolality gradient is mediated through eater reabsorption in descending limb and Na+ reabsorption in the ascending limb
54
What is the vasa recta permeable to?
Both water and solutes (K+, Cl-, Na+)
55
How does the composition of the tubule filtrate change as it enters the medulla?
Water diffuses out and salts diffuse in (filtrate is hyper osmotic) (Descending Loop of Henlé)
56
What are the two main parts of the DCT?
Macula densa: linked to the juxtaglomerular complex | 2nd part: convoluted tubule
57
What is the connecting tubule? | not present in all textbooks
Connects the end of the DCT to the collecting ducts
58
How does ADH function in the nephron?
Binding of ADH to v2 receptors on principal cells causes synthesis and insertion of aquaporin 2 into the PM. This causes water reabsorption and less diaeresis
59
What are the main functions of the DCT?
``` Solute reabsorption Very low water permeability (unless AQP2) dilution of tubular fluid Acid-base balance Secretion of NH3 ```
60
What are the 2 main cells present in the collecting ducts?
Intercalated cells | Principal cells
61
What is the histology of the collecting ducts?
cuboidal epithelia | very few mitochondria
62
What is the function of intercalated cells in the collecting ducts?
Acidification of urine | Acid-base balance
63
What is the function of principle cells in the collecting ducts?
Role in Na+ balance | Regulation of ECF volume
64
Where is ADH synthesised and stored?
Synthesized in hypothalamus | stored in posterior pituitary
65
What triggers ADH release?
Change in plasma osmolality as detected by osmoreceptors in the hypothalamus
66
What can be used to determine serum urea levels?
BUN = blood urea nitrogen test
67
What is the relative osmolality of the tubular fluid as it enters the collecting ducts?
Hypo-osmotic | ~100 mOsm/L
68
What determines the level of dilution of tubular fluid as it travels down the collecting ducts?
Plasma osmolality and therefore ADH secretion | This will determined the permeability of the tubular epithelia in the collecting ducts
69
Which components are reabsorbed or not in the collecting ducts in the absence of ADH?
Ducts impermeable to water and urea | Na+ reabsorption continues and tubular fluid becomes more dilute as it flows along duct
70
What are the main causes of hyperuricaemia?
= elevated uric acid (urate) levels in blood, often caused by reduced excretion of uric acid in urine Ciclosporin Alcohol Nicotinic acid Thiazides (diuretics) Loop diuretics Ethambutol Aspirin Pyrazinamide this often caused by acidosis (eg, DKA, EtOH or salicylate intoxication, starvation ketosis). The organic acids that accumulate in these conditions compete with urate for tubular secretion
71
What are the main regions of the adrenal cortex?
mnemonic: GFR-ACD G: zona Glomerulosa (outside) secrete mineralocorticoids e.g. aldosterone (A) F: Zona Fasciculata (middle) secretes glucocorticoids mainly cortisol (C) R: Zona retincularis (inner) secreted androgens, mainly dehydroepiandrosterone (DHEA) (D)
72
What are the main mediators of the RAAS system? What are the functions of each?
renin angiotensin II aldosterone
73
What are the actions of renin?
an enzyme that is released by the renal juxtaglomerular cells in response to reduced renal perfusion renin secretion stimulated by hyponatraemia, sympathetic nerve stimulation hydrolyses angiotensinogen to form angiotensin I
74
What are the actions of angiotensin II?
produced by conversion of angiotensin I by ACE (ACE produced in lungs) causes vasoconstriction of vascular smooth muscle leading to raised blood pressure vasoconstriction of efferent arteriole of the glomerulus → preserves GFR. Ang II stimulates thirst (via the hypothalamus) stimulates aldosterone and ADH release increases proximal tubule Na+/H+ activity
75
What are the functions of aldosterone?
released by the zona glomerulosa in response to raised angiotensin II, potassium, and ACTH levels causes retention of Na+ in exchange for K+/H+ in distal tubule
76
What cell type in the kidney produces renin?
juxtaglomerular cells
77
What are juxtaglomerular cells?
specialised smooth muscle cells found mainly in the walls of afferent arterioles
78
What are the 3 cell components found in the juxtaglomerular apparatus?
- juxtaglomerular cells - macular densa cells - extraglomerular mesangial cells
79
Where are podocytes found?
in the Bowman's capsule in the kidney | they wrap around the glomerular capillaries
80
What are the filtration slits in the Bowman's capsule?
= spaces between the foot processes of podocytes
81
What is the function of the macula dense cells?
- to detect tje Na+ Cl- concentration of the fluid in the tubular lumen
82
What happens if low concentrations of NaCl are detected in filtrate by the macular dense cells?
- increases secretion of renin | - vasodilation of afferent arterioles
83
Which factors stimulate renin secretion?
- hypotension (reduced renal perfusion) - hyponatraemia - sympathetic nerve stimulation - catecholamines - erect posture
84
Which factors reduce renin secretion?
Drugs: - beta blockers - NSAIDs
85
How do beta blockers reduce renin secretion?
by blocking b1 adrenoreceptors in the kidney these are found in the smooth muscle cells in the (juxtaglomerular cells when they contract they release renin, so when this is blocked, no renin is released)
86
What are the ideal features of substances used to measure GFR?
- inert - free filtration from plasma at the glomerulus (i.e. not protein bound) - not absorbed or secreted at the tubules - constant [plasma] during urine collection e.g. inulin, creatinine

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