Renal Flashcards
(115 cards)
1
Q
What are the main functions of the kidney?
A
- Remove waste products
- Regulate fluid balance and blood pressure
- Regulate electrolytes
- Regulate body fluid pH
- Regulate blood cell count
- Contribute to calcium homeostasis
- Detoxify free radicals
- Gluconeogenesis in times of starvation
2
Q
Describe the general size of the kidney - mass, length and width
A
130-160g
10-12cm long
5-7cm wide
3
Q
Describe the deep layer of renal capsule
A
- Smooth and transparent
- Dense irregular connective tissue
- Continuous with outer layer of ureter
- Trauma barrier
- Maintains kidney shape
4
Q
Describe the middle layer - adipose capsule of kidney
A
- Fatty tissue
- Trauma barrier
- Maintains kidney position
5
Q
Describe the superficial layer of the kidney - renal fascia
A
- Dense irregular connective tissue
- Anchors kidney to abdominal wall surrounding structures
6
Q
Describe the renal lobes
A
- 1 renal pyramid
- Overlaying area of renal cortex
- 1/2 of each adjacent renal column
7
Q
What is the order of renal arteries / vessels?
A
Renal artery segmental arteries Interlobar arteries Arcuate arteries Interlobular arteries Afferent arterioles Glomerular capillaries Efferent arterioles
8
Q
What is the order of renal veins /capillaries? Smaller to large
A
Peritubular capillaries Interlobular veins Arcuate veins Interlobar veins Segmental veins Renal veins Inferior vena cava
9
Q
Describe the nephron
A
- Functional unit of the kidney
- Each afferent arteriole supplies one nephron
- Blind ended tubes - renal corpuscle and renal tubule
10
Q
Describe the glomerulus
A
- Ball of capillaries supplied by afferent arteriole
- Initial site of urination production
- Drained by efferent arteriole
- 200um
11
Q
Describe the bowmans capsule
A
- Site of blind end nephron
- Outer parietal layer that is continuous with renal tubule outer layer
- capsular space - where filtrate collects
- Inner visceral layer composed of podocytes with envelope glomerular capillaries
12
Q
Describe the renal tubule
A
- PCT
- Loop of henle
- Distal tubule
- Collecting duct
13
Q
Describe cortical nephrons
A
- Glomeruli in outer 2/3 of cortex
- Short loops of henle
14
Q
Describe the juxdamedullary nephron
A
- glomeruli in inner 1/3 of Cortex
- long loops of henle which pass into deep medulla
15
Q
Describe the PCT
A
- Early part is convoluted
- Late part is straight
- 15 mm long
- Outside diameter 70um
- Columnar/cuboidal epithelium
16
Q
Describe the loop of henle
A
- U shaped loop
- Descending / ascending limbs
Thick segments - Simple cuboidal epithelium
- initial part of descending limb
- all of ascending limb
- metabolically active
Thin - Simple squamous epithelium
- Lower part of descending limb
- low metabolic activity
- High permeability to water
17
Q
Describe the juxtamedullary apparatus
A
- Macula densa - thick ascending limb
- Juxtaglomerular cells - afferent arteriole smooth muscle cells
18
Q
Describe the DCT
A
- Early part of thick ascending loop of henle
- Late part cuboidal - principal cells - ADH, intercalated cells, Aldosterone
19
Q
Describe the collecting ducts
A
- Cells very similar to late distal convoluted tubule
- Receives fluid from approx 6 distal tubules
- In medulla pair to form ducts of belini which drain into minor calyces
20
Q
Describe body fluid components and their percentages
A
Extra cellular 35%
- Interstitial fluids 25%
- PLASMA 8%
- Transcellular fluid 2%
Intracellular 65%
21
Q
Describe the intracellular fluid component (ICF)
A
- Virtual - made of cells (lots of )
- Unifying similarities
- contained. by cell membranes
- K+ = major cation
- proteins and phosphate are major anions
22
Q
Describe the extracellular fluid component (ECF)
A
- Any non intracellular compartment
- Na = major cation
- Chloride and bicarbonate = major anions
Has several sub compartments - plasma fluid - fluid within vasculature
- 70ml per litre of plasma composed of protein and lipid
ISF - interstitial fluid
23
Q
Describe the interstitial fluid
A
- Occupies interstitial space
- Separated by plasma fluid by capillary endothelium
- Bathes the cell and link between ICF and blood plasma
- Virtual
- Reasonably low in protein
- Excess ISF drains into plasma fluid compartment via lymphatic system
24
Q
Describe trans cellular fluid (TCF)
A
- Separated by plasma by additional epithelial layer Specialised functions
- urine
- CSF
- Lymph
- GI contents and secretions
- Synovial fluid
- Compartments of eye
25
Describe the dilution principle
Use of known quantity of dye to target compartment
| - After equilibrium measure the dye concentration
26
How do you measure dye concentration ?
- Make solutions of known concentration
- measure light intensity of solutions
- Plot conc vs light intensity calibration curve
27
Describe osmoality
Analogues to the mole for non dissociating substances it is identical to the mole
Osmoality mosmol kg H2O = Number of ions a solution dissociates into x molar concentration
28
What are the osmoalities of glucose and NaCL ?
```
Glucose = 1 mmol /kgH2O
NaCL = 1 mmol /kgH2O x 2 as dissociates so 2 mosmol/kgH2O
```
29
Describe body fluid osmolality
- Kept constant at around 280-300 mosmol/kg H2O
- Kidney plays major regulatory role
- ICF x ECF osmoalities are identical because H2O can readily cross cell membranes
30
What is osmotic pressure?
Equal to hydrostatic pressure and represents pressure required to prevent net movement of water across a semipermeable membrane
31
Describe isotonic and isomotic
Isotonic - does not cause change in cell volume
| Isomotic - solutions have the same osmolality
32
What is plasma protein oncotic/ colloid pressure?
- Osmotic pressure exerted by plasma proteins
- Large impermeant anions
- Important in transcapillary fluid dynamics
Represented by pie symbol
33
Give the Gibbs donnas effect equation
(Diffusable cations x Diffusible anions ) for side one
Times
(Diffusible cations x Diffusible anions) for side 2
34
Describe bulk flow
- Passive solute movement
- Solvent drag
- Occurs in vessels - vasculature, lymph vessels, renal tubules
- occurs from filtration across capillary membranes
35
Describe starling forces
Forces determine capillary filtration and reabsorption
- 90% due to diffusion
- 10% starling forces
36
Describe the ideal capillary for starling forces
1. Hydrostatic pressure dependent on -
- Arterial blood pressure
- Extent of transmission
- Venous pressure - resistance to flow
2. Plasma protein colloid pressure
- 25 mmHg
- constant as plasma proteins are effectively impermeable
- plasma protein are effective osmoses as they are impermeant
37
Describe glomerular filtration
- Produces ultra filtrate of plasma
- Filtration is modified along renal tubule until it becomes urine in the collecting duct
3 layered filter
- Endothelium
- basement membrane
- Podocytes
38
Describe the endothelium of glomerular filter
- Fenstrated capillaries - leakier than normal
| - Blocks cells and platelets
39
Describe the basement membrane of glomerular filter
- Secreted by podocytes
- Main filtration barrier
- Collagen and glycoproteins
- Negatively charged
40
Describe the Podocytes of glomerular filter
- Maintain basement membrane
- Complex structures
- Interdigitating foot processes - pedicles
- Negatively charged glycocalyx coating
- May act as supplementary filtration barrier via slit membranes
- Phagocytic escaping cells and macromolecules
41
Describe filtration characteristics of glomerular filtrate
- Free filtration below 7000Da
- Virtually no filtration above 7000Da
- Negative charges prevent filtration of most proteins
- Glucose, amino salts and urea are freely filtered
42
Describe how to calculate net filtration pressure (NFP)
Because glomerular filtration rate is directly proportional to net filtration rate can sub equation with a filtration coefficient
= Kf (coefficient) Pcap - PColloid bowmans capsule (pie bc) - PColloid capillary (Pie cap)
43
What are the values for Pbc, Pcap and Pie cap
Pbc - bowmans capsule hydrostatic pressure - 10 mmHg
Pcap - capillary hydrostatic pressure - 45mmHg
Piecap - capillary protein colloid oncotic pressure - 25mmHg
44
What are the factors affecting glomerular filtration rate?
- kf - filtration coefficient
- Capillary hydrostatic pressure
- Capillary oncotic pressure
- Bowmans capsule hydrostatic pressure
- Bowmans capsule oncotic pressure
45
Describe regulation of Renal blood flow
- Renal blood flow is 1.1 litres /min
- Not all of it is filtered
- Only 600ml of 1.1 litres of blood is filterable as a rest of volume is cells
- thus 600 ml represents renal plasma flow rate
46
Describe tubuglomerular feedback
- Loop of henle/ DCT regions pass close to renal corpuscle
- Contacts afferent and efferent arterioles -juxtaglomerular apparatus
- High GFR
- Sensed by macula densa
- macula densa inhibits nitric oxide secretion
- Decreased nitric oxide causes vasoconstriction of afferent arteriole
- Returns GFR to normal range
- Normal NaCL levels and fluid flow in distal tubules restored
47
Describe neural regulation of renal blood flow and glomerular filtration rate
- Rich sympathetic innervation to kidney
- Fibres to afferent arteriole wall
- Tonic activity is low
- Innervation has little effect
48
Describe what increased nerve activation leads to for RBF and GFR
- vasoconstriction of afferent arteriole
- Reduces RBF and GFR
- conservation mechanism
- GFR can be as low as A FEW ML per min
49
Describe medullary hypertonicity
- Generated by countercurrent multiplication
- INTERACTION BETWEEN LOOPS OF HENLE AND DISTAL TUBULES AND COLLECTING DUCTS
- Facultative water handling in collecting ducts due to ADH
Note to future Isabel - you couldn't be bothered to retype the caps
50
Describe the permeabilities of H2O of the ascending and descending loops of the loop of henle
```
Ascending = not permeable
Descending = Permeable
```
51
Describe countercurrent multiplication
- 200 mosmol/kg H2O difference between ascending loop and descending loop - small transverse osmotic gradient
- Multiplied into larger longitudinal gradient by counter current arrangement via hairpin bend
52
Describe Facultative H2O handling
- According to need in DCT and collecting ducts
- Collecting duct = cortical and medullary and DCT are relatively impermeable to water Urea and NaCl
- ADH increases H2O permeability of segments according to need
53
Describe what happens as ADH presence increases
- Increases H2O reabsorption in cortical collecting duct, fluid osmolality increases from 90 to 290 mosmol/kg H2O
- Remaining fluid enters medullary collecting duct for further h2O reabsorption
- Too much reabsorption in medulla would negate medullary hypertonicity hence majority occurs in cortical collecting duct
54
Describe urea countercurrent multiplication
- Urea is freely filtered at glomerulus
- 50% of urea passively reabsorbed in PCT
- urea concentration increases in descending loop and along loop owing to passive diffusion from interstitium
55
Describe the steps of urea recycling
- H2O leaves cortical collecting duct urea conc increases
- ADH activates urea uniporter in medullary collecting duct
- Urea diffuses along gradient from medullary collecting duct into interstitium
- Urea diffuses along gradient from interstitium into Thick ascending limb
- Urea travels along tubule to DT / cortical collecting duct and cycle repeats
* stimulates larger water reuptake by the descending limb
56
Describe long vs short nephrons
- 15% are long - juxtamedullary
- 85% are short - cortical
- all nephrons drain into collecting ducts which pass through medulla
- Can achieve concentrated urine from all nephrons
57
Describe proximal tubular function
- Reclaims useful filtered substances
| - Most reabsorption occurs in PCT involving Na transporters
58
Describe Na symporters and anti porters
Symporters - two or more solutes cross membrane in same direction
Antiporters - Two or more solutes cross membranes ion opposite direction
59
Describe transport maximum
- Transports have upper capacity limit
| - Measured in mg/min
60
Describe solute reabsorption
- H2O reabsorption occurs via osmosis
- proximal tubule - H2O reabsorbed with solutes
- Collecting ducts - H2O needs driven
61
Describe Na handling in PCT
- Na transporters achieve near 100% reabsorption of organic solutes
- 80-90% bicarbonate
- 65% H2O
- 50% cl-
62
Describe plasma osmoality
- 280-290 mosmol/kg h2O
63
Describe ADH
- Vasopressin
- Nonapeptide
- Synthesised in supraoptic and paraventricular nuclei (SON and PVN) located in hypothalamus
- 1/2 life 15 mins and degraded in the liver and kidneys
- Part of precursor molecule 166a
64
Describe ADH movement post synthesis
- Moves from SON/ PVN to posterior pituitary - neurohypophysis
- moves in axons of hypothalamohypopyseal tract
- progressively cleaved during movement
- strand with neurophysiology in nerve terminals
- Released into blood system when required
Plasma osmolality is main release stimulus
65
Describe osmoreceptors
- Located near SON
- Threshold for activation is 280 mosmol/kg H2O
- Small amount of ADH released if plasma osmoality rises linear response
66
Describe haemodynamics as ADH stimuli
- Via baroreceptors - low pressure/ volume
- Less sensitive need 10-15% blood vol drop to activate
- response is exponential
- Drugs effect BP so can affect plasma ADH levels
67
Describe nausea as ADH stimuli
- Instant + profound
| - Plasma ADH increases 100-1000 fold
68
What are 5 stimuli for ADH
1. Haemodynamics
2. Nausea
3. Hypoglycaemia
4. Hypoxia
5. Angiotensin
69
Describe the mechanism of ADH action
- principal cells V2 receptors on basal membrane
- ADH occupies V2 receptor
- Activates adenylate cyclase via Gs protein cAMP
- cAMP activates protein kinase PKA
- Pka phosphorylates and activates non functional aquaporin 2 water channels
- Active aquaporin 2 channels inserted into apical membrane
70
Describe aquaporin insertion and activation
- Causes water permeability to increase
- Water reabsorbed
- Urine is concentrated
71
Describe the pelvic nerve micturition reflex (wee)
- Bladder fills - rugae unfold
- pressure increases as urine vol increases
- Stretch receptors in bladder activate pelvic nerve afferents
- pelvic nerve efferent relax internal urethral sphincter
- urination urge communicated to higher centres
72
Describe voluntary control of micturition
- achieved by integration with higher centres -pons - via pudendal nerves
- Pudendal nerves keep external urethral sphincter closed
- Voluntary inhibition of pudendal nerve activity releases external sphincter
- urine flow
73
Describe effective circulating volume (ECF)
Compartment of blood which is perfusing the tissue
74
Describe renin release stimulation mechanism
- Stored in juxtaglomerular apparatus
- Increased sympathetic nerve activity initiated by baroreceptors
- Decreased wall tension, afferent arteriole
- Decreased Na delivery to macula densa
Caused by decrease in ECV by decreased Na
75
Describe the macula densa
- Releases prostaglandins I2 (PI2)
| - Stimulates granular cells to release renin into blood
76
What is the primary hormone in Na regulation?
Angiotensin 2
77
What are the 5 changes that occur with angiotensin 2 release?
1. Vasoconstriction - infrarenal and systematic
2. Increase of proximal tubular Na reabsorption
3. Aldosterone release from zone glomerulosa in adrenal cortex which increases distal tubular Na reabsorption
4. Increase thirst
5. ADH release - water retention
78
Describe the adrenal gland removal causes
- Loss of Nacl from body via urine
- Extracellular na content falls
- ECF volume reduced
- Circulatory collapse
79
Describe aldosterone and stimuli for release
- Synthesised by zone glomerulosa of adrenal gland
- Steroid hormone synthesised from cholesterol
Release
- Decrease in plasma Na concentration
- Increase in plasma K concentration
- Decrease in ECV via angiotensin 2
80
What are the effects of aldosterone?
- Stimulates na reabsorption in collecting duct
- Stimulates K secretion in collecting ducts
- Stimulates H+ secretion in collecting ducts
- Promotes Na+ reabsorption in gut and sweat glands
81
Describe atrial natriuretic peptide
- 28 aa hormone from 126 aa pro hormone
- release from atrial cells in response to atrial stretch
- Act at ANP receptors
- Promotes Na loss in urine
82
Describe the mechanism of action for atrial natriuretic peptide
- Inhibits collecting ducts Na-K ATPase
- Inhibits aldosterone secretion
- Reduced renin release, indirectly inhibiting aldosterone release
- Promotes vasodilation ion afferent arterioles and increases GFR
- Decrease in Na reabsorption
83
Describe urodilation
- Originates in kidney
- Almost identical to ANP with 4 additional aa's
- Actions identical to ANP
- Natriuretic
84
Describe dopamine
- Synthesised in proximal tubule
- Inhibits Na-k ATPase
- Inhibits Na-H anti port
- natriuretic
85
Describe adrenomedullin
- 52 aa peptide synthesised in the kidney
- Increase GFR
- Decrease Na tubular reabsorption
- Natriuretic
86
Describe a small pH change effect on nerve excitability, enzyme activity and K+ homeostasis
1. Nerve Excitability
- Acidosis - decreases CNS
- Alkalosis - Increases CNS
2. Enzyme activity
- r group amino acid chain vital to correct folding, pH change affects folding
3. K+ homeostasis
- Protein handling and K+ linked
- Increase H+ (acidosis )
- Decrease H+ leads to hypokalaemia (alkalosis )
87
Describe three neutralisations of carbonic acid in the body
1. Blood buffers
2. Respiratory compensation
3. Renal compensation
88
What is blood pH dependent on?
- HCO3- conc
| - CO2 conc
89
Describe the haemoglobin buffering system
- Buffers metabolically produced CO2
- H+ mopped up by reduced haemoglobin
- Haemoglobin reduced after O2 delivery to cells
- In lungs O2 = high, liberates CO2 remaining excess acid
90
Describe the plasma protein buffering system
- In ECF small buffering made by proteins
- Proteins are amphoteric
- Most important buffer in ICF where protein conc= high
91
Describe the phosphate buffering system
- Minor role in ECF due to low concentration
- Second only two proteins in ICF acid-base balance
- Good urinary buffer under normal conditions as little reabsorption
92
What's the Henderson hasselbalch equation?
Predicts if pH decreases PCO2 increases
| - Most CO2 removed by lungs
93
Describe acidosis
- Plasma H+ increases
- Less HCO3- filtered as it is buffering the H+
- Renal H+ secretion increases
- Urine is more acidic
94
Describe alkalosis
- Plasma H+ decreases
- More HCO3- filtered as it is not required to buffer H+
- Not all HCO3- is reabsorbed because H+ availability is limiting factor
- Urine is more alkaline
95
Describe H+ buffering with Ammonia
- Ammonium ion formed, secreted in the kidney as weak base
- Ammonia produced from glutamine metabolism
- Up regulated during acidosis
- Ammonia in collecting duct mops up urinary H+ during acidosis
96
Describe H+ buffering with phosphate
- capacity is limited unless in acidosis where capacity is exceeded
97
Describe compensation vs correction
Compensation
- Immediate
- Corrects pH change only
- PCO2 and HCO3- sacrificed to restore pH
Correction
- Complete restoration of pH, PCO2 and HCO3-
98
What are 4 disorders of acid base balance?
1. Respiratory acidosis
2. Respiratory alkalosis
3. Metabolic acidosis
4. Metabolic alkalosis
99
Describe respiratory acidosis
| Cause, Uncompensated result, compensated result and clinical cause
```
Cause
- retention of CO2 - hypoventilation
Uncompensated result
- pH decrease, HCO3- increase
Compensated result
- Increases HCO3- reabsorption
- Secretion of Ammonia
- HCO3- remains elevated
Clinical cause
- Drug induced depression of respiratory centres
- Pulmonary oedema
- Emphysema
```
100
Describe respiratory alkalosis
| Cause, Uncompensated result, compensated result and clinical cause
```
Cause
- loss of CO2 - hyperventilation
Uncompensated result
- pH increase, HCO3- decrease
Compensated result
- Decrease reabsorption of HCO3-
- Decreased ammonia secretion
- HCO3- remains depressed
Clinical Cause
- Anxiety
- Aspirin poison
- High altitude
```
101
Describe metabolic acidosis
| Cause, Uncompensated result, compensated result and clinical cause
```
Causes
- loss of HCO3- of H+ to plasma
Uncompensated result
- pH decreases, HCO3- decreases
Compensated result
- Respiratory compensation
- Increased ventilation
- Renal compensation completes in restoration of pH by increasing reabsorption of HCO3-
Clinical Cause
- Diabetic ketoacidosis
- Diarrhoea - loss of HCO3-
- Heavy exercise and lactic acid
- Renal failure - reduced proton secretion
```
102
Describe metabolic alkalosis
| Cause, Uncompensated result, compensated result and clinical cause
Causes
- addition of HCO3- or loss of H+ from plasma
Uncompensated result
- pH increase, HCO3- increases
Compensated result
- Respiratory compensation increase in ventilation
- partially restores pH
- Renal compensation completes the restoration od pH by decreasing reabsorption of HCO3-
Clinical cause
- Ingestion of antacids
- Vomiting - loss of HCL
103
Describe the negative feedback loop for erythropoietin increase caused by plasma hypoxia
```
Plasma hypoxia
Messangial/tubular cells
Plasma erythropoietin
Bone marrow stem cells
pro erythroblasts
Erythrocytes
```
104
Describe renal failure
- Less EPO produced
- Anaemia developed
- synthetic EPO available however costly £2500-£5000 per patient per year
105
Describe erythropoietin
- Hormone that stimulates erythropoiesis
| - 80% produced in the kidney by mesangial and tubular cells
106
Describe tubular handling of calcium
- 50% of plasma Ca2+ bound to albumin
- 5% of filtered ca2+ appears in urine
- Rest is reabsorbed
107
Describe Ca2+ handling in PCT
- Ca2+ reabsorption parallels Na and H2O
- 60% is passively reabsorbed
- Pentubular transport not determined - Ca ATPase and Ca/Na anti port - 3Na for 1 Ca2+
108
Describe ca2+ handling in the loop of henle
- 20-25% is passively reabsorbed
109
Describe ca2+ handling in DCT and collecting duct
- 5-10% is reabsorbed
110
Describe the regulation of calcium reabsorption
Regulated by parathyroid hormone and vitamin D
- PTH increases plasma ca2+
Raised by
- liberation of Ca2+ from bone
- indirectly decrease renal excretion of Ca2+
- indirectly increase intestinal ca2+ absorption
111
Describe how ca2+ is directly liberated in bone
- PTH increases number and activity of osteoclasts via action on osteoblasts
- osteoclasts mediate bone resorption
- bone resorption = breakdown of bone matrix and therefore elevating plasma Ca2+
112
Describe how plasma Ca2+ is increased by decreases in excretion
- Vitamin D3 steroid - active from calcitriol
- Decreases Ca2+ excretion
- Increases intestinal reabsorption and mediates indirect effects of PTH
113
What are the most important effects of PTH and calcitriol?
PTH - effect on bone
| Calcitriol - Intestinal
114
Describe calcitromin / calcitriol
- Peptide hormone
- Synthesised in parafolicular cells of thyroid gland
- Released when plasma Ca2+ is increased
- Antagonises actions of PTH
- promotes laying of bone
115
What are some symptoms of osteomalacia and rickets caused by vitamin D deficiency?
- Bone pain and tenderness
- Skeletal deformities - bow legs, bony bumps on the ribs, skull and pelvic deformities
- Increased tendency towards bone fractures
- Enlarged joints
- Dental deformities
- Decreased muscle tone
- Impaired growth and short stature
