Renal Flashcards
The kidneys are served by the renal artery and the renal vein. Which serves oxygenated blood and which serves deoxygenated blood?
Artery - oxygenated
Vein - deoxygenated
The kidneys lie in the peritoneal cavity with the intestines and the liver. True or false?
False - they lie in the back of the abdominal wall
What are the three functions of the kidneys?
Homeostasis
Excretion
Endocrine
The kidneys are involved in the production of _________ which is important in the production of RBCs
Erythropoietin
Blood flows into the nephron via the efferent arteriole. True or false?
False - through the afferent
What is glomerular filtration?
The movement of molecules from plasma in glomerulus into Bowman’s space
The afferent arteriole is narrower than the efferent arteriole. True or false?
False - efferent is narrower
Plasma filters from glomerulus into Bowman’s space through 3 layers. What are they?
Capillary endothelium Basement membrane Capsule cells (podocytes)
What is meant by the glomerular filtration rate?
The volume of fluid filtered into Bowman’s capsule per unit time
GFR can determine the stage of chronic kidney disease. True or false?
True
What effect does chronic kidney disease have on GFR?
As chronic kidney disease worsens, GFR decreases and albuminurea increases
What can be administered IV to measure kidney function?
Inulin
Inulin is a polymer of sucrose. True or false?
False - polymer of fructose
Inulin is not absorbed nor secreted by the nephron. True or false?
True
The amount of inulin that is filtered into the Bowman’s capsule is equal to the amount that is excreted in the urine. True or false?
True
Other than inulin, what can be used to measure renal function?
Creatinine
Creatinine is produced by muscles. True or false?
True
Creatinine is secreted by the nephron. True or false?
True
What three paratmeters are needed to measure renal clearance?
Rate of urine production
Urine concentration of drug
Plasma concentration of drug
What is renal clearance defined as?
The volume of plasma from which a substance is completely removed per unit time
What is ABCG2 also known as?
BCRP
What is ABCB1 also known as?
P-gp
MRP is an uptake transporter. True or false?
False - efflux transporters
Name 3 efflux transporters
P-gp
BRCP
MRP
Which uptake transporters does methotrexate bind to?
OCT1
OAT1
Which efflux transporters clear methotrexate?
MRP2, MRP4 and ABCB1
Pivastatin and rosuvastatin are recognised by which uptake transporter?
OAT3
Pivastatin and rosuvastatin are cleared by which efflux transporter?
BCRP
Fexofenidine is recognised by which uptake transporter?
OAT3
Fexofenidine is effluxed by which transporter?
ABCB1
Which uptake transporter does digoxin bind to?
OATP
Which transporter is digoxin effluxed by?
ABCB1
What is the aim of diabetes treatment?
Reduce plasma glucose
How can the amount of glucose in the plasma be reduced?
Block the glucose transporter so that glucose reabsorption is reduced and glucose is eliminated in urine instead
Name a SGLT2 inhibitor that is licensed for the treatment of type 2 diabetes
Dapagliflozin
70% of filtered Na+ is reabsorbed in the ________ ______
proximal tubule
All sodium is reabsorbed early on in the nephron. True or false?
False - some of it is reabsorbed later on in the nephron in the collecting ducts
What is the role of the antiporter protein?
Na+ reabsorption - entry of Na+is couple to H+
How do the kidneys help in regulating the acid-base balance?
They secrete H+ which passes out in the urine and produce HCO3- which can be used as a buffer
Which other organ does the kidney work with in order to regulate the acid-base balance in homeostasis?
Lungs
What happens in respiratory acidosis?
There is a build up of H+ in the protons and so blood through the lungs is compromised as a result of the fibrous mass. The kidneys correct this disorder by increasing the excretion of H+ secretion
Which hormone regulates Na+ ions?
aldosterone
Where is aldosterone produced?
In the adrenal cortex
What effects does aldosterone have on Na+?
When aldosterone is secreted, it tells cells in the collecting ducts to increase the number of Na+ channels in the apical membrane
It also tells cells to increase the number of pumps in the basolateral membrane
Which system stimulates the secretion of aldosterone?
Renin-angiotensin system
What happens in the renin-angiotensin system?
Low levels of Na+ are sensed by the kidney juxtaglomerular cells. These produce renin
Angiotensinogen is secreted by the liver in low levels. Renin converts angiotenisinogen into angiotensin I.
Angiotensin I is converted to angiotensin II by ACE which is secreted by kidney and lung capillary cells
Angiotensin II circulates in the body, gets to the adrenal cortex and stimulates it to produce aldosterone
What are ACE inhibitors indicated for?
Hypertension
Heart failure
Name to diuretics
Spironolactone
Amiloride
What will a patient with excessive aldosterone experience?
Increased Na+ reabsorption, increased water reabsorption and this is associated with congestive heart failure
Which diuretic is a aldosterone analogue?
Spironolactone
What is the mechanism of action of spironolactone?
Binds to the aldosterone receptor, inhibiting the binding of aldosterone and so it can’t tell cells to increase Na+ channels or pumps and so water and Na+ pass out of the urine as a result
What is the mechanism of action of amiloride?
Binds to Na+ channels on the apical membrane and so blocks Na+ entry into the cell. This results in Na+ and water remaining in the tubular fluid and passing out in urine
Where in the kidney do diuretics act?
cortical duct
Aldosterone binds to cells in the cortical collecting duct. True or false?
True
What effect does hypertension have on nephrons?
They are reduced
There are gap junctions between epithelial cells of the proximal convoluted tubule. True or false?
False - tight junctions
How much Na+ reabsorption is the PCT responsible for?
60-70%
What is the role of the counter current multiplier in the descending loop of Henle?
It is a way of concentrating interstitial fluid in the renal medulla i.e. concentration of the interstitial fluid increases as LoH descends
Why is it important that the concentration of interstitial fluid is hypertonic outside the filtrate?
So water can pass out into the blood
Are cells in the descending loop of Henle permeable to water?
Yes - water diffuses out of the lumen down a conc gradient
Are cells in the thick ascending loop of Henle permeable to water?
They have low permeability to water
How much Na+ is reabsorbed in the ascending loop of Henle?
20-30%
How does Na+ move in the ascending loop of Henle?
Na+ is pumped out of the cell via the basolateral membrane Na/K pump - this creates a gradient for Na+ to cross the apical membrane via the Na/K/Cl transporter
Is the distal convoluted tubule permeable to water?
No - impermeable to water
Does Na+ reabsorption take place in the distal tubule?
Yes - reabsorbed down a conc gradient
How is water reaborbed in the collecting tubule?
Via aquaporin channels
How do aquaporin channels function?
they are stored in vesicles - ADH binding to vasopressin receptors causes their insertion into the apical membrane. They can remove as much as 15% of filtered water, making urine considerably hypertonic to plasma
What mediates Na+ reabsorption in the collecting tubule?
Aldosterone
All diuretics are secreted by cells of the PCT into the lumen. True or false?
False - most but not spironolactone
Loop diuretics are powerful. Roughly how much of filtered Na+ is excreted?
15-25%
How do loop diuretics work?
They inhibit the Na/K/Cl carrier in the thick ascending limb of loh
What type of diuretic is furosemide?
Loop diuretic
Is the Na+/H+ exchanger affected in loop diuretics?
No - so Na+ drives H+ excretion
There is an increase in magnesium and calcium excretion as a result of loop diuretics. True or false?
True
What are the indications for loop diuretics?
acute pulmonary oedema liver cirrhosis and ascites CHF Renal failure Hypertension Hypercalcaemia
What are the side effects of loop diuretics?
Hypotension Hypokalaemia Metabolic alkalosis Gout Hearing loss
Where is the site of action of thiazide diuretics?
Distal tubule
What is the moa of thiazide diuretics?
Inhibit the Na+/Cl- cotransporter
What is the problem with thiazide diuretics?
Reduced blood volume leads to increase in renin release which in turn increases AngI and AngII production which are vasoconstrictors - increased BP - limiting the hypotensive effect during chronic dosing
What are the indications of thiazide diuretics?
Hypertension
Mild-moderate heart failure
Oedema
Nephrogenic diabetes insipidus
What are the side effects of thiazide diuretics?
Increased urinary frequency
Erectile dysfunction
Hypokalaemia
Impaired glucose tolerance
Thiazide diuretics are only effective orally. True or false?
True
Chlotalidone and metolazone are which types of diuretics?
Thiazide
Name a thiazide diuretic
Indapamide
What foods/drink increase K+?
Bananas
Instant coffee
Fruit juice
Where is the site of action of K sparing diuretics?
Collecting tubule
Name a K sparing diuretic
Spironolactone
Eplerenone
What are the indications for spironolactone
Ascites
Oedema
Severe heart failure
What is the indication for epleronone?
Adjunct in patients with LV failure following IM
What are the side effects of K sparing diuretics?
hyperkalaemia
GI upset
Gynaecomastia
What is the moa of triamterene and amiloride?
Inhibit Na+ reabsorption by blocking luminal Na+ channels in collecting tubules
What are the indications for amilodride and triamterene?
Adjunct to loop/thiazide for hypertension and CHF
Which drugs are not safe to use in patients with renal impairment or drugs which increase K?
Amiloride and triamterene
Amiloride has a slower onset than triamterene and is less well absorbed. True or false?
True
Amiloride is excreted unchanged in the urine. True or false?
True
Name an osmotic diuretic.
Mannitol
What are the indications for mannitol?
Cerebral oedema
Raised intra-occular pressure
Acute renal failure
The kidneys regulate red blood cell production. True or false?
True
The kidneys regulate bone-mineral metabolism. True or false?
True
What is the definition of CKD?
Kidney damage for over 3 months as evidenced by structural abnormalities with normal or decreased GFR (>60ml/min/1.73)
GFR < 60ml/min/1.73 with or without kidney damage for over 3 months
How is CKD diagnosed?
Blood/urine tests or imaging
All CKD progresses to end-stage kidney disease eventually. True or false?
False
What does a GFR <15ml/min/1.73 indicate?
Kidney failure
What are the markers of kidney disease?
Albuminuria Urine sediment abnormalities Electrolyte and other abnormalities due to tubular disorders Abnormal histology History of kidney transplantation Structural abnormalities
What are the advantages of using serum creatinine as a marker of kidney disease?
It is produced at an almost constant rate
Readily available to most labs
Easy to do - single blood sample
What are the disadvantages of serum creatinine?
It is proportional to muscle mass so need to know age, sex, body size, ethnicity, gender etc.
Value usually used in equations to estimualt GFR
What is the best measure of overall kidney function?
GFR
What is the normal GFR value?
~100ml/min - works like a %
What correction factor needs to be applied when calculating creatinine based GFR?
1.159 for patients of African-caribbean or African family origin
How does a decreased muscle mass influence GFR?
It will result in overestimation
How does an increased muscle mass influence GFR?
It will lead to an underestimation
Which type of GFR test is cautioned with uncontrolled thyroid disease?
Cystatin C-based GFR
What are some risk factors of CKD?
Hypertension
Diabetes
AKI
Cardiovascular disease
Proteinuria is a non-modifiable risk factor of CKD. True or false?
False - modifiable
Dyslipidaemia is a modifiable risk factor of CKD. True or false?
True
What are some causes of CKD?
Diabetes Pyelonephritis Glomerulonephritis Polycystic kidney disease Kidney stones
What are some early interventions that could be taken to delay or prevent end stage renal disease?
Reduce proteinuria
BP control
Glycaemic control for diabetes
What should the BP target be for patients with renal disease, diabetes or conditions that affect the heart and circulation?
130/80
What complications could arise as a result of CKD?
Renal anaemia
Mineral bone disease
Acidosis
CVD
Erythropoiesis stimulating agents should be used in patients with anaemia of CKD to correct levels of hb. True or false?
False - not recommended
What are the causes of CKD anaemia?
Uraemia increases the risk of GI bleeding
N+V reduces risk of appetite
Shortened life span of RBCs
What is the target Hb level for adults and children over 2 in CKD anaemia?
100-120g/l
What is the target Hb level for children under 2 in CKD?
95-115g/l
When should phosphate binders be taken for CKD patients with high phosphate?
Immediately before or with meals
What causes pruritis in CKD patients?
High phosphate levels and/or uraemia
How is pruritis in CKD treated?
Low phosphate diet, phosphate binders. Symptoms can be controlled using antihistamines
How can acidosis as a result of CKD be corrected?
Oral sodium bicarbonate
What causes nausea in CKD and how is it treated?
Build up of toxins - can be treated using anti-emetics e.g. metaclopramide
Which class of diuretics should be avoided in moderate to severe renal impairment (eGFR <20mls/min)?
Thiazide
AKI is irreversible. True or false?
False - frequently reversible
What are the risk factors for AKI?
Hypovolaemia Hypotension Diabetes Liver disease Heart failure
How is AKI detected?
A rise in creatinine of 26 micromols/l or more within 48 hrs
A fall in urine output to less than 0.5ml/kg/hr for more than 6 hrs in adults and more than 8 hrs in children
What causes AKI?
Majority is pre-renal due to reduced renal perfusion i.e. dehydration, hypotension, sepsis
Post-renal - prostate enlargement
Renal - NSAIDs, ACEI
What are the two types of dialysis?
Haemodialysis
Peritoneal dialysis
What is the advantage of HD?
good removal of electrolytes
What are some disadvantages of HD?
Anaemia Hypotension Expense Pain Pruritis Access is surgically induced
What are the advantages of PD?
Fluid balance less tight
Renal function declines less rapidly
What are the disadvantages of PD?
Constipation
Infections
Electrolyte removal not as good
What causes hypotension as a result of dialysis?
Too much fluid being removed too quickly
Kidney transplantation is cheaper than dialysis. True or false?
True
What are the common combinations of immunosuppressive agents in AKI?
Ciclosporin/tacrolimus +/- prednisolone
Ciclosporin/tacrolimus +/i prednisolone +/- azathioprine
Prednisolone+/- azathioprine
The therapeutic range of ciclosporin, tacrolimus and sirolimus changes over time since transplant. True or false?
True
What drugs increase ciclosporin/tacrolimus levels?
Amiodarone
ABs (e.g. erythromycin, clarithromycin, ketaconazole), diltiazem
What drugs decrease ciclosporin/tacrolimus levels?
Rifampicin Carbamazepine Phenytoin Phenobarbitone St Johns Wort
What affect does oedema and ascites have on volume of distribution?
Increase vd of highly water soluble drugs or protein bound drugs resulting in lower plasma concentrations
What 3 things does renal excretion depend on?
GF
Renal tubular secretion
Re-absorption
What is the first choice analgesic in kidney disease?
Paracetamol
Morphine metabolites accumulate in renal failure. Name some alternative opioids
Oxycodone
Fentanyl
(not codeine as that is metabolised to morphine)