REN Flashcards
1
Q
What is a fluid?
A
A substance that deforms under a shear stress. Importantly, one in which water or fat/lipid is the solvent.
2
Q
What are the key compartments?
A
Intracellular water
Interstitial water- filling the space between cells, amongst the extracellular matrix
Fat
Plasma
Transcellular fluid- separated from extracellular fluid by a membrane e.g. CSF, peritoneal fluid, aqueous humour
3
Q
How do you calculate the volume of distribution?
A
Inject a substance known to distribute into a given compartment and calculate the Vd. The volume of fluid required to contain the total amount of drug in the body at the same concentration as is present in the plasma.
Vd= Q/Cp where Q is amount of drug and Cp is the plasma concentration of the drug.
4
Q
How is plasma volume estimated?
A
Labelled proteins are injected intravascularly; Evan’s Blue
5
Q
How is extracellular fluid volume estimated?
A
36Cl-, thiosulphate, thiocyanate, inulin.
6
Q
What is plasma?
A
Fluid component of the blood, usually represents about 55% of blood by volume. Rest of the volume is occupied by cells.
7
Q
What is haematocrit?
A
Measure of the proportion of blood occupied by cells. (45%)
8
Q
What are the constituents of the body fluids?
A
E=Extracellular, I=Intracellular Na+ E>I K+ E<i>I Cl- E>I HCO3- E>I Glc E>I Osmolarity ~285mOsmkg-1</i>
9
Q
What is Ca2+ in the blood like?
A
Half bound to albumin so any change in albumin will change the total Ca concentration without changing the free Ca conc.
Free Ca is biologically active and more interesting, body regulates free Ca not total Ca.
10
Q
What is an osmole?
A
Measure of the number of molecules that a compound dissociates into when dissolved in solution.
11
Q
What is the difference between osmolality and osmolarity?
A
Osmolality is the number of osmoses per unit mass of the solvent. (Osmkg-1)
Osmolarity is the number of osmoles per unit volume of the solution. (Osml-1)
12
Q
What is osmotic pressure?
A
The force per unit area required to oppose the movement of species along its conc grad. It is the amount of pressure required to oppose osmosis.
13
Q
Define isosmotic
A
Two solutions have the same osmolality
14
Q
Define isotonic
A
Applying the solution to cells will not cause a net movement of fluid
15
Q
What is oncotic pressure?
A
The osmotic pressure due to proteins in the capillaries
16
Q
What is a normal renal plasma flow rate?
A
600mlmin-1
17
Q
Which forces drive filtration in the glomerulus?
A
1) Hydrostatic- higher hydrostatic pressure (50mmHg) in the capillaries drives fluid out, much higher than that in most capillaries.
2) Osmotic/oncotic pressure- higher osmotic pressure in the capillaries due to plasma proteins impedes the flow.
18
Q
What are the main ways to locally increase the pressure in the glomerular capillary?
A
Dilate the afferent arteriole
Constrict the efferent arteriole
19
Q
What are the main ways to locally increase the pressure in the glomerular capillary?
A
Dilate the afferent arteriole
Constrict the efferent arteriole
20
Q
What is the equation for osmotic pressure?
A
Osmotic pressure = nCRT (nC=osmolality, 0.28osmkg-1 and R= ideal gas constant 0.082Latmmol-1K-1 and T= temperature, 310K)
21
Q
What are the glomerular barriers to diffusion?
A
1) Endothelial cells of the glomerular capillaries- with fenestrations between them
2) Glomerular basement membrane- fixed negatively charged proteins
3) Epithelial cells of Bowman’s capsule
22
Q
What are podocytes?
A
Epithelial cells of Bowman’s capsule, they have small pedicels that project and interdigitate with their neighbours to form another barrier to the movement of fluid.
23
Q
Which molecules are filtered in the kidney?
A
Most molecules less than 10kDa in size, Na+, K+, Mg2+, Ca2+, Cl-, HCO3-, glucose and urea.
Larger molecules may be found, if + or if glomerular damage causes leaking
24
Q
What is a normal GFR?
A
120mlmin-1 or 180lday-1
25
What is the use of hydrostatic P in the Bowman's space?
Helps to drive movement of fluid through the rest of the kidney.
26
What is the filtration fraction?
Proportion of plasma flow filtered by the glomerulus. GFR/RPF
27
How can GFR be measured?
Measured using substances that are freely filtered but neither secreted or absorbed in the tubes.
Substance can be injected intravenously or produced by the body at a steady rate (creatinine).
28
How is creatinine in urine measured? How is the rate of production worked out?
Amount: Ccru x V
Rate: (Ccru x V)/t
29
How do you work out GFR?
GFR x Ccr,p
(Ccru x V)/t = GFR x Ccr,p
GFR = (Ccru x V')/(Ccr,p)
30
What is an empirical GFR estimate?
Taking a blood sample. Relies on info that Cr production is constant with age and correlated with age sex and mass. At equilibrium, rate of production = rate of loss through kidney so GFR varies inversely with Ccrp.
eGFR = k/Ccr,p
31
What happens to GFR with age?
Progressively lose nephrons and GFR falls causing Cr to rise.
32
What is the significance of proteinuria?
Glomerular dysfunction. Key feature of a key set of renal failures which when sufficiently severe, constitute nephrotic syndrome. Glomerulonephritis.
33
What is the transport in the proximal convoluted tubule?
Selective distribution of ion channels, exchangers and pumps on apical and basolateral membranes are key to directional ion movement. Movement is trans and paracellularly. Movement of Na+ creates an osmotic P gradient for the movement of water transcellularly and paracellularly. This segment of the tubule is water permeable implying that the filtrate is nr isotonic with the interstitial space which in the cortex means that it is effectively isotonic with plasma. By the end of the tubule about 70% of water is reabsorbed.
34
What are the different forms of transport in the PCT?
Uses the movement of Na+ down its electrochemical gradient to drive the movement of other substances like glc and amino acids.
Uses the Na+/K+ ATPase to move Na+ out of the cell on the basolateral membrane.
35
How does water move in the PCT?
Both paracellular route and the transcellular route through AQP1. Paracellularly by net outward hydrostatic and osmotic forces.
36
What is the fate of each of the following in the PCT?
a) Absorbed? b) Conc at end of tubule
1) Inulin
2) Urea
3) Chloride
4) Na+ and K+
5) HCO3-
6) Amino acids
7) Glucose
1) No / Higher
2) Weakly / Higher
3) Weakly / Higher
4) Yes / Same
5) Yes / Lower
6) Strongly / Much lower
7) Strongly / Much lower
37
How is glucose absorbed in the PCT?
90% transported by low affinity/high capacity SGLT2, rest by high affinity low capacity SGLT1. Basolateral transport by GLUT2 or GLUT1.
Maximal tubular load of glucose, about 380mgmin-1
38
How are amino acids absorbed in the PCT?
Plasma amino acid concentration is 2.5-3.5mM. Transport is Tm limited. Many different transporters, mostly cotransporters using the Na+ gradient.
39
How is HCO3- absorbed in the PCT?
Reaction with excess H+ entering through a Na+/H+ exchanger. Rate at which eq is achieved is increased by carbonic anhydrase. Basolateral transport uses Na+/3HCO3- transporter.
40
What is acetazolamide?
Blocks carbonic anhydrase so is a weak diuretic and is used in glaucoma and mountain sickness prophylaxis. It can cause a metabolic acidosis, makes urine alkaline.
41
How is Cl- absorbed in the PCT?
Both active and passive transport. Active- through antiproton for other anions (HCO3- or HCOO-).
Because HCO3- is also absorbed in the PCT, with its charge balanced by Na+ absorption, less Cl- is moved than Na+. Water is reabsorbed with these which means that [Cl-] increases along the tubule so as this increases the paracellular movement of Cl- is driven by the conc grad.
42
What happens to albumin in the PCT?
Albumin that has been filtered binds to the plasma membrane of the tubule and is endocytose then catabolised into its amino acids for subsequent recycling in the body.
43
What is secreted in the PCT?
Penicillin, PAH, furosemide, negative charge often comes from carboxylates of sultanates. Ions compete for excretion. Basolateral membranes- organic anion transporters, luminal membrane- multi drug resistance- associated protein, MRP.
44
What is the key function for the thick ascending limb of the loop of Henle?
To create a hyperosmolar interstitial space in the medulla to drive water loss from the descending limb and cortical collecting duct. It pumps out Na and Cl and is water impermeable.
45
What are the functions of the thin descending limb?
Permeable to water which leaves the filtrate due to osmotic force.
46
What does the thick ascending limb do?
Sustains an osmotic gradient of about 200mOsmkg-1.
Uses the Na+/K+/2Cl- cotransporter to move ions out of the filtrate. Common abbreviation NKCC2. K+ recycling through the apical membrane is necessary to ensure transporter can maintain its role in transporting large quantities of Na+ and Cl-.
47
What is furosemide?
Acts in the ascending limb of the loop of Henle- loop diuretic.
Blocks Na+/K+/2Cl- co transporter.
Allows up to 20% of filter Na+ to be excreted causing enormous natriuresis and diuresis. It is used in cardiac failure and renal failure.
Side effects- K+ loss and subsequent hypokalaemia leading to cardiac dysrhythmias particularly when administered with digoxin. Other side effects include hypovolaemia, mild metabolic alkalosis and loss of Mg2+ and Ca2+.
48
What is the countercurrent mechanism for osmolality?
1. Process (same text as syllabus notes, but points listed separately)
a. The active reabsorption of Na+ and Cl- in the ascending thick limb of juxtamedullary nephrons combined with the thick limb impermeability to water results in an increased osmolality in the renal medulla.
b. The increased medullary interstitial osmolality draws water from the descending thin limb, progressively concentrating the fluid remaining in the tubular lumen.
c. As this fluid passes around the hairpin turn and flows into the ascending limb, it loses NaCl into the interstitium by passive diffusion in the ascending thin limb and by active transport in the ascending thick limb.
d. As a result, interstitial fluid throughout the whole medulla becomes hyperosmotic and the fluid leaving the ascending thick limb and entering the distal tubule is hypoosmotic.
2. Because this process occurs as the fluid is flowing along the loop of Henle and exchange takes place between the interstitium and fluid streams moving in opposite directions (descending and ascending) and because osmolality increases progressively with depth in the medulla, the mechanism is termed countercurrent multiplication.
3. The interstitial osmolality is further increased by the accumulation of urea (explained later).
49
What are thiazides?
```
Act in distal tubule
Block Na+/Cl- co transporters
Moderately effective diuretics
Used as an antihypertensive
As a diuretic in conjunction with furosemide
```
50
What is spironolactone?
Acts in the collecting tubules and ducts, blocks the effect of aldosterone. Moderately effective diuretics. Used in heart failure (K+ sparing diuretic)
51
What are the side effects of spironolactone?
Gynaecomastia, menstrual disorders, testicular atrophy hyperkalaemia.
52
What is urea countercurrent multiplication?
Urea concentration rises in the DCT and cortical collecting duct because water is reabsorbed and they are impermeable to urea. In the medullary collecting duct, urea diffuses out of the tubule as ADH increases permeability and expression of UT-A1. Urea adds to high osmotic P in the medulla and aids water reabsorption.
53
What is urine concentration and flow regulated by?
ADH
54
What is ADH?
Synthesised in the hypothalamus, released from hypothalamic neurones in the posterior pituitary, acts in the distal tubule and collecting duct to increase water permeability by increasing AQP2 on the apical membrane.
55
How does ADH act?
V2 receptor GPCR, leads from Gs to AC to cAMP via ATP. From cAMP there is a long term and a short term pathway.
Long term- Nucleus +ve transcription to AQP2 synthesis to vesicles containing AQP2 to apical membrane.
Short term- PKA increases insertion.
56
What is the osmolality in the nephron when there is no ADH?
```
PCT- 285
LOH- 600 down to 90
DCT- 90
Collecting duct- 60
In the absence of ADH, water cannot cross this segment so osmolality doesn't equilibrate with the cortex at 285. Ions are pumped out and end up with diluted urine.
```
57
What is the osmolality in the nephron with maximum ADH?
```
PCT- 285
LOH- 1400 down to 90
DCT- 285
Collecting duct- 1400
Osmolality can now equilibrate with the cortex so water can leave and exchange across a segment. Water leaves to equilibrate with the medulla so high osmolality urine.
```
58
What are osmolytes?
Play a role in maintaining fluid balance by staying within cells to protect against a high osmotic environment.
59
What is diabetes insipidus?
Loss of ADH secretion (central) or loss of sensitivity to ADH (nephrogenic). Puts are unable to produce concentrated urine leading to polyuria, dehydration and hypovolaemia.
60
What are the causes of central diabetes insipidus?
Head injury, tumour, infection
61
How is central diabetes insipidus managed?
ADH analogue, desmopressin,
62
What are the causes of nephrogenic diabetes insipidus?
Toxicity, hypercalcaemia, genetic mutation
63
How is nephrogenic diabetes insipidus managed?
Thiazide diuretic
64
How does thiazide diuretic work?
Protection against hypernatraemia, encourages PCT reabsorption, increased AQP expression. Paradoxical use
65
What is SIADH?
Syndrome of inappropriate ADH. High ADH from head injury, become hyponatraemic and produce very concentrated urine. Commonly caused by a head injury. Treat by fluid restriction and give urea.
66
What is the vasa recta?
The efferent arteriole from the glomerulus runs into portal vessels which form a hairpin loop deep into the medulla. This takes water and solvents from the interstitial space after absorption by the tubules and also provides the tubules with substances to secrete. Osmotic pressure in the vasa recta varies because the capillaries are permeable and the osmotic P changes with the local interstitial osmolality. Dilutes the interstitium in the descending limb and concentrates it in the ascending limb.
67
What is the countercurrent in the vasa recta?
Passive movement. Net movement inwards due to low hydrostatic pressure in the capillaries, high oncotic pressure in caps and high hydrostatic pressure in the turgid interstitial space. Flow rate in the descending limb decreases as water leaves and increases in the ascending limb as water enters.
68
What are the 2 mechanisms of auto regulation in the kidney?
1) Myogenic response (regulating total renal blood flow)
2) Tubuloglomerular reflex (regulates a single nephron;s GFR but affects renal blood flow if many single nephrons are affected)
69
What is the myogenic reflex?
Regulates total renal blood flow. When the BP increases and the elastic efferent vessels are stretched, there is a reflex causing vasoconstriction. This increases the resistance and decreases the flow to the glomerulus. Only a small change in radius is needed for a large response. The stretch activated cation channels depolarise smooth muscle by increasing Ca influx causing a contraction. Maintains GFR and reduces the impact of the high systolic P.
70
What is tubuloglomerular feedback?
A high Na+ is detected in the DCT by the macula densa. These release ATP which is broken down into adenosine. Adenosine causes vasoconstriction of the afferent arterioles which decreases the RPF and GFR.
71
Why might auto regulation not happen in real life?
Renal blood flow is also influenced by innervation and circulating hormones. If there is a trauma, auto regulation will not occur.
72
What is the renal innervation?
dense plexus of nerves. A lot of sympathetic efferents releasing NA and causing vasoconstriction. A key stimulus is hypotension, decreased RBF to retain volume and shunt to muscles.
73
What is the equation for RPF?
RPF= (V. x Cpah,u)/ Cpah,p
74
Define clearance.
The volume of a body fluid cleared of a substance per unit time. It judges the method of elimination or metabolism of a drug.
75
What is the equation for clearance?
Cl= (V. x Cx,u)/ (Cx,p) where (V. x Cx,u)= excretion rate
76
What are the meanings of the following renal clearance values?
a) 0
b) GFR
e) ~RPF
f) >RPF
a) Neither filtered nor secreted e.g. large proteins
b) Filtered and partially reabsorbed
c) Filtered and reabsorbed
d) Filtered and partially secreted
e) Filtered and secreted
f) Produced in the kidney
77
How is whole body clearance calculated?
Measure change in concentration of a drug over time.
| Cl= Dose/ Area under the curve
78
What is the equation to work out conc at a certain time?
C= Cmaxe^-kt
79
What is the equation for half life?
T1/2= (ln2)/k
80
What is the relationship between clearance and Vd?
Cl=kVd
81
Where is osmolality detected?
Anterioventral third ventricle where BBB is incomplete
82
What happens to the AV3V neurones?
They project into the supraoptic and paraventricular parts of the hypothalamus and respond to an increase in osmolality by increasing the release of ADH from the posterior pituitary. ADH is synthesised in the cell bodies from the pheromone and cleaved as it descends down the pituitary. Co released with carrier peptide neurophysin.
83
What is thirst?
Inadequate water intake increases plasma osmolality, detected at AV3V and projected to the median pre optic area and increases thirst.
84
What is proof for tonic ADH release?
Decreased osmolality due to binge drinking causes suppression of ADH.
85
What is the maximum urine osmolality?
1400mOsmkg-1
86
What is the juxtaglomerular aparatus?
Late distal tubule in association with renal afferent arteriole. Granular cells in the afferent arteriole, thickening of the wall in the DCT which is the macula dense.
87
What is RAAS?
Renin angiotensin aldosterone system
- Low Na+ in the DCT
- Macula dense cells detect
- Juxtaglomerular cells
- Angiotensinogen VIA RENIN to angiotensin I
- Angiotensin I VIA ACE to angiotensin II
- Angiotensin II then triggers 2 pathways:
i) - Aldosterone release from the adrenal cortex
- Increased Na+ reabsorbtion by DCT and collecting duct.
- Increased Na+ and water reverses the fall in distal Na+ delivery.
- Increased GFR then negatively feeds back.
ii) - Efferent arteriole vasoconstriction
- Increased GFR
88
What are the 2 main physiological triggers for aldosterone release?
ATII and hyperkalaemia
89
What inhibits the RAAS and why?
To control BP
- ACE inhibitors
- AT1 receptor antagonists
- Aldosterone receptor antagonists
- Renin inhibition
90
What is the main receptor for ATII?
AT1 receptor. Coupled through Gq linked to increased IP3/DAG and increased Ca 2+ release.
91
What are the 5 key actions of ATII?
1) Vasoconstriction
2) Increase in Na+/H+ exchange in the PCT and hence proximal Na+ and H2O reabsorption
3) Increased aldosterone release from adrenal cortex which increases distal Na+ absorption
4) Cause ADH release
5) Causes thirst
92
What causes renin release?
Decreased BP, increased simp activity. Sensed in afferent arteriole causing a fall in the wall tension and releasing renin.
93
What are the 3 actions of sympathetic activation on the afferent arteriole?
1) Vasoconstriction upstream of the granule cells causes a further fall in the P sensed by the cells and amplifies the fall in wall P generated by a fall in BP
2) Direct stimulation of renin release from granule cells
3) Afferent constriction drops hydrostatic P and decreases GFR
94
Why is ADH released following haemorrhage?
Decreased cardiac filling, baroreceptor reflex activation, ATII release ADH.
Increased water reabsorption and maintenance of circulating volume.
Lowers osmolality because it doesn't retain Na+ so acute response to haemorrhage causes hponatraemia.
95
What is ANP?
Atrial natriuretic peptide. Released by the atria when they detect increased venous return. Acts on ANPab receptors in the kidney and increases cGMP.
Inhibits Na+/K+ ATPase activity which dilates the afferent glomerular arteriole and increases GFR. Decreases NaCl cotransport and ENaC
Increased Na+ excretion in the urine.§
96
What do prostaglandins do with respect to Na+ excretion?
Increase it
97
What are the normal values for pH, HCO3- and Pco2 in the arterial and venous systems?
pH: Arterial= 7.4 Venous= 7.35
HCO3-: Arterial= 24mM Venous= 25mM
Pco2: Arterial= 40mmHg Venous= 46mmHg
98
What is the Henderson Hasselbalch equation?
pH = pK + log10([base]/[acid])
99
When does net hydrogen ion production occur?
When
- ATP is hydrolysed
- During anaerobic respiration, with the production of lactate
- During the production of ketones
- During the ingestion of acids
100
How is metabolically produced H+ removed from the body?
Reaction with HCO3- to produce CO2 which is exhaled. BUT this results in a loss of HCO3-.
101
How is HCO3- reabsorbed in the PCT?
CA catalyses the reaction with H+ to form H2O and CO2 which pass through the membrane. Inside the cell there is the further reaction back to HCO3- and H+. The HCO3- leaves the basal membrane with one Na+ to three HCO3-.
102
What does the reabsorption of HCO3- in the PCT depend on?
H+ in the PCT and the Na+/H+ exchanger. Transport limited process means that nearly all of the filtered bicarbonate is reabsorbed under resting conditions but that an excess of HCO3- is not reabsorbed.
103
What is the main mechanism of H+ secretion in the DCT?
Primary active transport through the apical H+K+ ATPase and H+ ATPase
104
How is H+ buffered in the filtrate?
Needs to be buffered in the filtrate to keep the concentration low. It can be buffered by hydrogen phosphate. H+ + HPO4 2- ----> H2PO4-
105
How are ammonium ions produced in the PCT?
Conversion of glutamine to glutamic acid and alpha ketoglutarate. NH4+ is in equilibrium with NH3 which, being small and uncharged is membrane permeable. NH4+ reforms in the tubule so is a reservoir for H+.
106
What are the key acid-base problems?
Respiratory acidosis
Respiratory alkalosis
Metabolic acidosis
Metabolic akalosis
107
What is respiratory acidosis?
Caused by hypoventilation, CO2 goes up so H+ increases and pH falls. Shift towards the dissociation of water and CO2 to HCO3- and H+. To compensate, the kidney increases the production of HCO3-, returning pH to normal.
108
What is respiratory alkalosis?
Caused by hyperventilation and high altitude. CO2 goes down so H+ goes down. H+ and HCO3- combine to shift towards the RHS of equation making H2O and CO2. To compensate, the kidney decreases the production and recovery of HCO3- and returns pH to normal.
109
What is metabolic acidosis?
Caused by renal failure, lactic acidosis, ketoacidosis and food poisoning. H+ increases so pH falls, HCO3- decreases OR H+ increases. To compensate, the respiratory system increases ventilation rate, decreasing CO2 and returning the pH to normal.
110
What is metabolic alkalosis?
Caused by vomiting, contraction alkalosis. H+ decreases so pH rises. HCO3- goes up or HCO3- goes up so H+ goes down.
H+ + HCO3- H2O + CO2
111
What is the anion gap?
Sum of positive and negative charges in our bodies are equal. But there is a gap between the number of cations and anions. The gap is usually measured as [Na+]-[Cl-]-[HCO3-]. It is exacerbated by the divalent cations (Ca2+ Mg2+) and is only partially explained by other well known anions (eg. HPO4-)
112
What does an increase in anion gap suggest?
That there is a high concentration of anions that are not being counted. e.g. lactate, ketones, sulphates, aspirin overdose.
113
What are the functions of the kidneys?
Homeostasis- osmoregulation, pH, BP, waste elimination, water homeostasis, electrolyte and acid base homeostasis.
Metabolic/ endocrine- synthesis of hormones, vitamin D, EPO, renin
Excretion of drugs and drug metabolites.
114
What is the traditional measure of kidney function?
Serum creatinine. Influenced buy gender, age, ethnicity, body mass, diet and exercise.It isn't sensitive to small changes in function.
115
What is CKD?
Chronic kidney disease, it is irreversible and progressive and staged 1-5. Each stage has a decreasing GFR. Stage 5 is kidney failure.
116
What is stage 5 CKD?
End stage renal failure, insufficient function to sustain life, needs haemo/peritoneal dialysis or transplantation and leads to death.
117
Which patients are most likely to get CKD?
Diabetes, hypertension, NSAIDs or multiple drugs, elderly.
118
How is CKD linked with socioeconomics?
The lower the affluence, the lower the GFR. Prevalence increases with a decrease in affluence and increase in deprivation.
119
What are the risk factors of CKD?
Age, hypertension, diabetes, smoking, poor education, black and indoasian populations.
120
What are the causes of CKD?
- Systemic diseases- diabetes, hypertension, atherosclrotic disease.
- Immune mediated diseases- membranous nephropathy, IgA nephropathy.
- Infectious diseases- HIV, HBV, HCV, TB
- Genetic diseases- polycystic ovaries, cystinosis
- Arterial disease- atherosclerosis
- Obstruction- tumours, stones, fibrosis
121
What is the pathology in CKD?
- Thickening of the basement membrane
- Mesangial expansion due to hypergycaemia stimulating increased matrix production in mesangial cells and stimulation of TGF-B release
- Glomerulosclerosis due to intraglomerular hypertension or ischaemic damage.
122
What is diabetic nephropathy?
Nodules form in the glomeruli
123
What can be complications with CKD?
- Anaemia
- Hypertension
- Disturbed Ca/phosphate homeostasis
- CVD
- Bone disease
- Abnormal handling of drugs
- Immune supression
- Bleeding tendency
- Complications of treatment
124
What are the 2 types of failure of fluid homeostasis?
- Inability to concentrate urine due to loss of diurnal rhythm of urine excretion, osmotic diuresis of surviving glomeruli and limited rate of water excretion.
- Inability to excrete water load- dilution hyponatraemia, oedema and hypertension
125
What is the treatment for fluid overload?
- Diuretics
- Restrict salt
- Fluid restriction
- Dialysis and transplant if all else fails
126
Why is there hyperkalaemia when GFR <10ml/min?
Excessive load, interference with potassium excretion, acidosis with volume contraction and diabetic nephropathy. There is an enormous functional reserve to excrete K+ but in severely low GFR cases.
127
What are the complications of hyperkalaemia?
- Alterations in membrane exctability, cardiac arrhythmias, ECG changes- tall T waves, long QRS interval, long PR interval and cardiac arrest.
128
What is the treament to prevent hyperkalaemia and hypernatraemia?
- salt restriction
- K+ restriction
Dialysis or transplant
129
What are the symptoms for metabolic acidosis?
Increased respiratory drive (breathless), chest pain, confusion, bone pain, demineralisation of bone
130
What is the treatment for metabolic acidosis?
Sodium bicarbonate, dialysis and transplant
131
What treatment prevents bone disease and ectopic calcification?
- Vit D supplements
- Phosphate restriction
- Phosphate binders
- Calcimimetics
- Parathyroidectomy
132
What are the impacts of anaemia in CKD?
- Impaired QOL, reduced exercise capacity and impaired cognition.
- Transfusion requirement, iron overload or blood borne infection
- Increased risk of left ventricular hypertrophy
- Increased CV disease in patients with CKD and anaemia vs those with CKD without anaemia
133
What is the treatment for renal anaemia?
Replace EPO with recombinant EPO
134
What are the mechanisms of hypertension?
- Sodium retention
- Volume expansion
- RAS activation
- Symp NS activity
- Endothelial dysfunction
It accelerates the decline of kidney function and contributes to a CVD risk.
135
What is the treatment for hypertension in CKD?
- salt retention
- diuretics
- RAS blockade
- antihypertensives
136
What happens when there is failure in excretory function?
- Metabolism of drugs impaired
- Increased risk of toxicity due to accumulaiton of a drug
- Insulin leads to hypoglycaemia
- Opiates lead to respiratory suppression
- Antibiotics lead to encephalopathy
- Sedatives lead to respiratory arrest
- Digoxin leads to arrhythmias
AVOID- just dose knowing the kidney function
137
Why does CKD progress?
Major modifiable risk:
- Uncontrolled underlying disease
- Hypertension
- Proteinuria
- Smoking
138
What are the clinical problems of K+ dysregulation?
Hyperkalaemia
CAUSES- end stage renal failure, crush injuries, blood transfusion, cytotoxic drugs, insulin deficiency, overuse of K+ sparing diuretics.
CONSEQUENCES- Cardiac dysrhythmias
TREATMENTS- K+ restricted diet, insulin and glucose
Hypokalaemia
CAUSES- Diarrhoea, furosemide, insulin overdose
CONSEQUENCES- Cardiac dysrhythmias
TREATMENTS- Treat the cause, give K+ IV or orally
139
Where are the sites of renal K+ exchange?
PCT- Reabsorption, passively and paracellularly with water
TAL- Through NKCC cotransporter but much of the K+ cycles back into the filtrate here
DCT to COLLECTING DUCT- Apical membrane ROMK K+ channel controlled by aldosterone and Ca activated K+ channel
Most diuretics increase the distal K+ secretions by both increasing distal Na+ delivery and by increasing the amount of water in the filtrate.
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What is the fate of filtered calcium?
- 20% of plasma free Ca2+ is filtered in the glomerulus, only 10% of total Ca is filtered. PCT- Moves transcellularly, proportional to water movement.
TAL- absorption, drive by + potential in the lumen.
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What is EPO?
Glycoprotein hormone, synthesised in peritubular fibroblasts in the renal cortex. Production and release is stimulated by hypoxia and mediated by the release of prostaglandins. Transcription stimulus is by HIF- hypoxic inducible factors.
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What are the actions of EPO?
Anti-apoptotic agent for erythrocyte progenitors. Binds to EPO receptors in the bone marrow and increases the production of pro erythroblasts which become erythrocytes.
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What happens to EPO in renal failure?
Levels fall leading to anaemia. Give EPO analogues.
