Clinical Renal and Hepatic Disease Flashcards
What are the different types of tests to diagnose liver disease?
Medical history
Blood tests
Imaging
Liver biopsy- local anaesthetic
Name the blood tests used for diagnosis of liver disease:
LFTs
Electrolytes
FBC- end stage causes bone marrow suppression
Viral screens- see if its hepatitis/ viral cause
Blood clotting- prothrombin time
Name the imaging tests used for diagnosis of liver disease:
Ultrasound
CT scan
MRI
Name the main LFTs used for liver disease diagnosis:
Aspartate transaminase (AST)
Alanine transaminase (ALT)
Describe the role of AST in the liver:
Role in gluconeogenesis
Catalyses reversible conversion of aspartate and alpha ketoglutarate to oxaloacetate and glutamate
Found in hepatocytes, but also other tissues including heart, brain and skeletal muscle
What is the reference range for AST?
5-40IU/L
Describe the role of ALT in the liver:
Also role in gluconeogenesis
Catalyses reversible transfer of an amino group from L-alanine to alpha ketoglutarate resulting in pyruvate and L-glutamate
More specific to liver
What is the reference range for ALT?
5-30IU/L
What do the levels of AST and ALT mean?
Very high levels in acute viral/toxic hepatitis
High levels in cholestatic jaundice/ cirrhosis
Ratio of AST/ATL useful in diagnosing different types of liver disease e.g AST/ALT more than 2 possibly due to alcohol injury, most other liver injuries ratio is less than 1
Name the non-main LFTs used for liver disease diagnosis:
Gamma glutamyl transferase (GGT)
Alkaline phosphatase (ALP)
What is useful about the GGT test?
Can be used as a use of alcohol consumption/ abuse
Levels drop after 3-6 weeks
Describe the role of GGT in the liver:
Catalyses transfer of gamma glutaryl moiety of glutathione to an a.a, peptide or water (forming glutamate)
Also in kidneys, pancreas and prostate
What is the reference range of GGT?
5-45IU/L
What do the levels of GGT mean?
Very high levels in biliary obstruction, lower increased levels in chronic alcohol or drug toxicity, hepatitis, cirrhosis or cholestasis
Describe the role of ALP in the liver:
Removes phosphate groups from nucleotides, proteins and alkaloids
Also in bone marrow, intestinal wall, renal tubules and placenta
What is the reference range of ALP?
20-100IU/L
What do the levels of ALP mean?
Very high levels in biliary obstruction
Describe the bilirubin test in blood tests for liver disease:
Reference range 0-17µmol/L
Jaundice occurs at more than 35µmol/L
Increases reflects depth of jaundice and useful for monitoring disease progression
Can measure total levels or difference conjugated/ unconjugated bilirubin
What is the difference between conjugated and unconjugated bilirubin?
Conjugated from the liver
Unconjugated from RBC/heme breakdown
Describe the plasma protein and albumin test in blood test for liver disease:
Reference ranges 60-80g/dL total protein
35-50g/dL albumin
Albumin is synthesised solely in the liver
Half life for plasma albumin is 20-26 days
Less than 20g/dL changes plasma protein pressure, leading to oedema
Why is the half life of albumin useful in determining?
As the half life is 20-26 days (long), a reduction can indicate long term damage due to extended half life which can’t be decreased immediately
What is the prothrombin time?
Reference range 10-15 secs
Increase PT when lack of clotting factors
PT depends on factor II,VII and X and will increase if these factors aren’t produced
If hepatocellular damage, liver can’t produce clotting factor as its unresponsive to vit K
If cholestasis increase in PT due to deficiency in bile salts responsible for vit K absorption so responsive to vit K
What is the treatment for cholestasis when PT is increased?
IV 10mg Vitamin K for 3 days
Describe the urea and ammonia test in blood tests for liver disease:
Reference range for urea: 2.5-7.8 mol/L
Reference range for ammonia: 16-60(M), 11-51(F) µmol/L
Urea decreases in liver disease
Ammonia increases in liver disease, hepative encephalopathy- due to failure of liver to convert ammonia to urea
What effects can liver disease result in?
Drug clearance
Biotransformation
Pharmacokinetics
What can liver disease cause alterations in?
Intestinal absorption
Plasma protein binding
Hepatic extraction ratio
Liver blood flow
Portal systemic shunting
Biliary excretion
Enterohepatic circulation
Renal clearance
Describe phase I metabolism and drugs metabolised there:
Oxidation e.g azathioprine
Reduction e.g halothane
Hydrolysis e.g atropine, pethidine
Describe phase II metabolism and drugs metabolised there:
Glucuronidation e.g paracetamol, morphine
Sulphonation e.g steroids
Acetylation e.g hydralazine, phenelzine
Methylation e.g nicotine
What is the extraction ratio?
Rate of drug removed by liver, depends on both the capacity to metabolise but also blood flow through the liver
Can be high or low
Name and describe drugs with a high extraction ratio:
Clearance depends on hepatic blood flow
Likely to require a larger decrease in dose
Chlomethiazole, lignocaine, morphine, propranolol, verapamil, metoprolol, pethidine
First pass metabolism, ER close to 1
Name and describe drugs with a low extraction ratio:
Clearance depends on metabolising capacity of the liver
Chloropropamide, phenytoin, diazepam, warfarin, atenolol, furosemide, prednisolone, lorazepam
ER close to 0
Name drugs and conditions which are Cyp450 inhibitors:
Cimetidine, ciprofloxacin, ethromycin, COCs, ketoconazole
CCF, cirrhosis, viral infections
Name drugs and conditions which are Cyp450 inducers:
Phenytoin, carbamazepine, phenobarbiton, primedonne, rifampicin
Smokers, heavy drinkers
Increase in GGT levels
Describe the pharmacodynamics in liver disease:
Increase sensitivity to drugs which:
-affect clotting/ bleeding, due to LD decrease clotting factor
-affect CNS, increase risk of hepatic encephalopathy
-diurects
-constipation
How can diuretics cause liver disease complications?
Hypervoleamia, decreases in K+, leads to increased risk of hepatic encephalopathy
How can consitpation cause liver disease complications?
Increase risk of hepatic encephalopathy as N waste products in GIT for increased period of time so increased risk of absorption
What is the treatment/ management for cirrhosis and end stage liver disease?
Low protein diet
Low Na+ and diuretics to minimise water retention
Draining of ascites fluid by paracentesis
Surgery to treat portal hypertension and decrease risk of bleeding
Medicines depending on disease and complications
Transplant
What are the lifestyle modifications in liver disease?
Lose weight and stop alcohol
What are the minor symptoms in acute alcohol withdrawal?
CNS hyperactivity resulting in insomnia
Tremulousness
Mild anxiety
GI upset
Headache
Diaphoresis (excessive sweating)
Palpitations
Resolves within 24-48 hrs
What are more severe symptoms in acute alcohol withdrawal, normally in chronic alcoholism?
Seizures- convulsions usually occur within 12-48 hrs of last drink
If untreated can lead to delerium tremens (DTs)
Alcoholic hallucinations- resolve within 24-48 hrs
Fluid and electrolyte abnormalities
Describe DTs in acute alcohol withdrawal?
DTs develop in 48-96hrs after last drink, results in hallucinations, disorientation, tachycardia, hypertension, hypothermia, agitation and diaphoresis, can be fatal
What is the treatment for acute alcohol withdrawal?
Symptom control and supportive care
Benzodiazepines
IV fluids
Nutritional supplementation
Frequent clinical assessment
Describe the use of benzodiazepines in acute alcohol withdrawal:
Control psychomotor agitation and prevent more severity
e.g chlordiazepoxide, oxazepam, decreasing regimen over 9 days
Lowest possible dose given to suppress symptoms without sedation
Seizures- IV lorazepam
Ideally don’t send home with supply as causes respiratory depression and dependence especially with alcohol
Describe the treatments for cholestatic pruritis:
Cholestryamine- first line:
ion exchange resin, binds to bile salts in the gut stop it being absorbed
Anti-histmaines:
non- sedating to avoid encephalopathy
Calamine lotion/ menthol in aqueous cream
How does ascties occur?
Earliest and most common complication of chronic LD- 50% within 10 yrs
Activation of RAS due to decrease in renal blood flow due to disordered liver anatomy
Increase in levels of aldosterone so fluid retention and also liver metabolises aldosterone so increase fluid
Chronic LD, decrease in albumin, decrease in osmotic pressure in plasma so fluid accumulation in abdomen
What is the treatment for ascites?
Diuretics
Bed rest
Na+ and fluid restriction
Paracentesis- physical draining of fluid
Aim for weight loss: 0.5-0.75kg decrease per day (up to 1-1.5kg per day if also peripheral oedema) -therapeutic monitoring
What are the consequences if the weight loss is too much in ascites?
Hypovolaemia - risk of encephalopathy
Hyponautramia
Hypokalaemia
Toxic monitoring
What are the diuretic treatments in ascites?
1st line= spironolactone as its an aldosterone antagonist
Add on= furosemide (loop) if no weight loss/ peripheral oedema
What is the initial treatment for Wernicke-Korsakoff syndrome?
IV Pabrinex (IV vit B/C preparations)
Infusion over 30 mins
2 pairs of ampoules TDS for 3-5 days
Need facilities for treating prophylaxis as potential serious allergic reaction
What is the additional treatment for Wernicke-Korsakoff syndrome?
Oral thiamine for treatment or prophylaxis
100mg TDS (regimen can vary)
Administered at same time as IV and then continue for 3-6 months after abstinence
What is the treatment for hepatic encephalopathy?
Lactulose
Rifaximin- add on when lactulose not working
Phosphate enemas- when lactulose CI
Avoid precipitating factors
Describe the use of lactulose in hepatic encephalopathy:
30-50ml TDS
Adjust to aim for 2-3 soft stools a day (therapeutic)
Disaccharide molecule, breaks down to form lactic acetic and formic acid so decreases pH of intestine, from 7 to 5, ionisation of N compounds to decreases absorption, alters intestinal flora (decreases ammonia producing bacteria), speeds up gut transit, less time for N and ammonia to sit in gut and be absorbed into system
What are the toxic monitoring parameters of lactose in hepatic encephalopathy?
Avoid diarrhoea casing dehydration and hypovolaemia
Describe the use of rifaximin in hepatic encephalopathy:
Semi-synthetic derivative of rifamycin
Decreases production/ absorption of gut ammonia
What are precipitating factors of hepatic encephalopathy?
Avoid dehydration
Hypokalaemia
GI haemorrhage
CNS drugs
High dietary protein
Constipation
What is the treatment for portal hypertension?
Aim to decrease portal BP and resting HR by 25%
Propranolol low dose and increase cautiously as undergoes 1st pass metabolism
Other vasodilators e.g nitrates
What is the treatment for bleeding oesophageal varices?
Resuscitation and correct hypovolaemia (blood transfusions, IV fluids)
Vasoactive therapy
Endoscope (camera down oesophagus)
-sclerotherapy (e.g ethanol amine to stop bleeding)
-ligation/banding
-balloon tamponade
-TIPS (transjugular intrahepatic porto systemic stent shunt)
Describe vasoactive therapy for the treatment of bleeding oesophageal varicies:
IV e.g vasopressin, terlipressin, octreotide
Started as soon as haemorrhage is suspected
Describe the treatment for prothrombin time:
PT is greater than 18seconds
Phytomenadione IV (vit K)- may not work if pt has severe liver disease
Avoid NSAIDs/ warfarin
Describe drug induced hepatotoxicity:
Over 900 drugs, toxins and herbs cause liver injury
Drugs cause:
-20-40% of all liver failure
-2-5% of hospitalised jaundice
-10% acute hepatitis cases
What are risk factors for drug induced hepatotoxicity?
Age e.g sodium valproate CI under 3
Sex- females 2x more likely
Alcohol ingestion
Pre-existing liver disease
Genetic facts
Other co-morbidities e.g HIV
Drug formualtion
What is the pathophysiologic mechanism for drug induced hepatotoxicity?
Disruption of the hepatocyte
Disruption of the transport proteins
Cytolytic T cell activation
Apoptosis of hepatocytes
Mitochondrial disruption
Bile duct injury
What are the two types of ADR?
ADR type A- intrinsic or predictable
ADR type B- idiosyncratic or unpredictable
Describe ADR type A reactions:
Reproducible injury in animals
Injury is dose related
Due to drug or metabolite
80% of all ADRs
e.g paracetamol or carbon tetrachloride
Describe ADR type B reactions:
Hypersensitivity or immunoallergenic response e.g phenytoin with fever, rash, eosinophilia
e.g chlorpromazine, halothane
OR
metabolic, idiosyncratic, indirect metabolite or offending drug
What are the LFT signs of drug induced hepatoxicity?
Many drugs can cause inconsequential rises in LFTs, if up to 2x upper limit then doesn’t require medicine
Liver damage has occurred when:
-ALT increased to more than 2x upper limit
-increased conjugated bilirubin more than 2x upper limit
-combined increased ALP and total bilirubin with one more 2x upper limit
What is the management for drug induced hepatotoxicity?
Drug withdrawal
Antidote if appropriate
Corticosteroids- evidence controversial, if LFTs still deteriorating 3 weeks after, or if hepatotoxicity remained 6 months after discontinuation
Supportive therapy
Yellow card report- serious report
What is the prevention for drug induced hepatotoxicity?
LFT monitoring
Patient eduction
-signs of liver damage e.g abdominal discomfort, malaise, nasuea
-OTC paracetamol, health/herbal remedies
What is the dosage of paracetamol that causes hepatotoxicity?
Accounts for more than 50% of acute liver failure
More than 15g leads to fatal hepatic necrosis
More than 7.5g risk of severe liver damage
More than 5g requires hospital admission and observation
What is the diagnosis for paracetamol toxicity?
Serum paracetamol concentration
What are the different phases in paracetamol hepatotoxicity?
Phase 1,2,3,4
What is phase 1 of paracetamol hepatotoxicity?
0.5-24 hours after ingestion
Asymptomatic or anorexia, N&V, malaise
What is phase 2 of paracetamol hepatotoxicity?
If left untreated
18-72 hours after ingestion
Right upper quadrant abdominal pain and tenderness, anorexia, N&V, possibly oliguria (decrease in urine)
What is phase 3 of paracetamol hepatotoxicity?
If left untreated
Hepatic phase 72-96 hours after ingestion
Continued symptoms, hepatic necrosis may be seen as jaundice, coagulopathy, hypoglycaemia, hepatic encephalopathy, possible acute RF, death from multi organ failure
What is phase 4 of paracetamol hepatotoxicity?
If left untreated
Recovery 4 days- 3 weeks
Complete resolution if survive phase 3 and complete resolution of organ failure
Describe the major route of paracetamol metabolism:
95% into paracetamol conjugates by glucuronide sulphates, then excretion in the urine
Describe the minor route of paracetamol metabolism in normal doses:
5% via Cyp450 metabolism
Into N-acetyl P benzoquinoneimine (NAPQI)- toxic
Normal doses, glutathione conjugates into non- toxic products and excretion in the urine
Describe the minor route of paracetamol metabolism in over doses:
5% via Cyp450 metabolism
Into N-acetyl P benzoquinoneimine (NAPQI)- toxic
In overdoses, glutathione stores become depleted, allowing NAPQI to accumulate and bind directly to hepatocytes causing cell damage= hepatotoxicity
Name the different treatments for paracetamol overdose:
N acetyl cysteine IV
Methionine oral, both replenish glutathione stores
Activated charcoal of gastric lavage within ONE hour
Describe N acetyl cysteine as a treatment for paracetamol overdose:
IV first line
Given during first 8 hours of overodse
Possible effective up to and beyond 24 hours, effectiveness decreases after 12 hours
Dosing depends on plasma paracetamol conc and time after ingestion
A= normal treatment line
B= enhanced risk line, for patients on enzyme inducers, alcoholics, malnourished, HIV
Name the systems of the renal system:
Aorta
Inferior vena cava
Left kidney- both found at the back of the abdominal cavity just below the ribcage
Right kidney- slightly lower due to presence of liver
Ureter
Bladder
Urethra
Describe the nephron:
1 million nephrons per kidney
What is eGFR?
eGFR, measuring renal function, looking at filtration rate from capillaries of glomerulus to Bowman’s capsule
Volume of fluid that filters into the Bowman’s capsule per unit time
Name the 4 functions of the kidney:
Excretory
Endocrine
Regulatory
Metabolism
Describe the excretory function of the kidney:
Excretes waste products and drugs
For certain drugs need to assess the extent of renal impairment
Make adjustments to dose/ drug choice
Avoid nephrotoxics
Describe the endocrine function of the kidney:
Erythropoietin production- stimulates RBC production in bone marrow
Renin production- BP control
PG production
Describe the regulatory function of the kidney:
Control fluid volume and composition
Regulate BP
Regulate blood pH
Describe the metabolism function in the kidney:
Vit D metabolism
Name the 2 different types of tests to assess renal function:
Plasma (blood)- more routinely
Urine
Name plasma tests for assessing renal function:
Creatinine (by product of protein metabolism)
Urea
eGFR
Name the urine tests for assessing renal function:
-Albumin:creatinine ratio (ACR)
-Osmolality- high particle conc= high osmolality
-Specific gravity- solute conc, higher gravity= more solutes- proteinuria/ microalbumina
-Haematuria- blood in urine
-Mid- stream urine (for UTI)
Describe creatinine as a test for renal function:
Freely excreted by the kidneys
Any level of renal impairment will cause increase in creatinine due to build up in the body as they kidneys are supposed to be excreting it out
Other factors can cause creatinine to rise, so rather than creatinine alone, can use creatinine clearance
Describe creatinine clearance (CrCl) as a test for renal function:
GFR roughly equal to CrCl
24 hour urine collection
CrCl (ml/min) = (urine Cr (µmol/L) x volume (ml))/ (plasma Cr (µmol/L) x time)
What are the problems with using CrCl using urine collection and what is the outcome?
Time delays and suspect accuracy of urine collection depending on where it is taken place
In practice use the Cockcroft and Gault equation
What is the Cockcroft and Gault equation:
CrCl (ml/min) = ((140-age) x weight x F)/ plasma Cr (µmol/L)
F= 1.23 males
F*= 1.04 females
What are the limitations of the Cockcroft and Gault equation?
Assumes average population data
Unsuitable for children and pregnancy
Renal function must be stable (plasma Cr stable)
What is the traditionally normal levels of Cr and CrCl?
Cr= 55-125 µmol/L
CrCl= 120 ml/min
Name 2 ways how eGFR can be calculated:
MDRD- Modification of Diet in Renal Disease equation
CKD-EPI- Chronic Kidney Disease Epidemiology Collaboration Formula
Describe the MDRD test to calculate eGFR:
4 variables used
Serum Cr
Age
Sex
Ethnic origin
Less accurate when more than 60ml/min/1.73m2 and overestimates for elderly
Describe the CKD-EPI test to calculate eGFR:
Most recommended
Same limitations as CrCl
Online calculator
Local laboratory calculations
Describe the race adjustments in eGFR equations:
Practice varies in x1.159 for Black ethnic groups as creatinine production is higher in black ethnic origin
Only found this to be advantageous in America so NICE has removed this recommendation
Name the different stages of renal impairment:
Stage 1(G1)- normal GFR
Stage 2 (G2)- mild impairment
Stage 3A (G3A)- mild to moderate
Stage 3B (G3b)- moderate to severe
Stage 4 (G4)- severe impairment
Stage 5 (G5)- established/ end stage
What is the eGFR value for stage 1 renal impairment?
More than 90
What is the eGFR value for stage 2 renal impairment?
60-89
What is the eGFR value for stage 3A renal impairment?
45-59
What is the eGFR value for stage 3B renal impairment?
30-44
What is the eGFR value for stage 4 renal impairment?
15-29
What is the eGFR value for stage 5 renal impairment?
Less than 15
What is the unit for eGFR and why?
ml/min/1.73m2
This is the normalised BSA
How would you calculate the GFR absolute?
Can use it to individualise someones GFR
= eGFR x (individual BSA/1.73)
Describe urea as a test for renal function:
Nitrogenous breakdown product of protein metabolism
Freely excreted by the kidney so a raise in blood levels suggest impairment
What is the normal and uraemia range of urea?
More than 15mmol/L= uraemia
Normal 1.7-6.7mmol/L
What are the symptoms of uraemia?
N&V
Puritis
What can blood urea levels also be increased by?
Dehydration
Muscle injury
Infection
Haemorrhage
Excess protein intake
So test should never be used alone
Describe the osmolality test for renal function:
Darker urine, more concentrated
Describe proteinuria test for renal function:
Albumin is a protein which is meant to be in the blood and not in the urine, so testing the urine for albumin is a predictor of renal disease development and adverse outcomes
How would you calculate the albumin: creatinine ratio (ACR):
Divide albumin (mg) by creatinine (g)
What is the ACR value showing renal failure in non-diabetics?
More than 70mg/mmol
What is the ACR value showing renal failure in diabetics?
More than 2.5mg/mmol in males
More than 3.5mg/mmol in females
Due to increased risk of developing renal disease
What is ACR used for?
To predict renal disease development and risk of adverse outcomes e.g CKD progression, AKI events and general mortality
What is the general classification of CKD?
Decreased GFR and increased ACR
Describe absorption of drugs in renal disease:
Uraemia decrease drug absorption via: D&V, GI, oedema
Reduced Ca absorption- due to less vit D activation
Hyperphosphatemia- kidney impairment struggles to excrete phosphate- phosphate binder treatment decreases some drug absorption
Describe distribution of drugs in renal disease:
Changes in distribution due to fluid accumulation so affect distribution of particularly water soluble drugs
Less protein binding
Less tissue binding
Describe how less protein binding affects the distribution of drugs in renal disease?
Phenytoin due to hypoalbuminemia and urea competition- less albumin for phenytoin to bind to
Increased levels, urea competes for protein binding sites so increased free phenytoin in blood
Describe how less tissue binding affects the distribution of drugs in renal disease?
Digoxin increases conc
Urea will compete with digoxin for tissue binding sites
Describe metabolism of drugs in renal disease:
Less vit D metabolised (less calcitriol production)
Less Ca absorption from gut and kidneys
Less insulin metabolism (T1D insulin requirements may be affected in RD)
Less elimination of pharmacologically active metabolites
Describe examples of active metabolites that aren’t eliminated as much due to renal disease:
Nor-pethidine- lead to CNS excitation and epileptic seizures
Morphine metabolites- can accumulate causing toxicity issues
Switch to alternative opioid e.g oxycodone which is less renally excreted
Describe excretion of drugs in renal disease:
Less excretion, need to modify doses of drugs which are renally excreted
Lower dose and/or increase dose interval- drug dependent
NO adjustment needed to loading doses
Describe ideal types of drugs in renal impairment:
Wide therapeutic index
Eliminated by the liver
Not affected by changes in fluid balance, tissue or protein binding
Not nephrotoxic
Describe the nephrotoxicity of a drug in renal disease:
Ideally not nephrotoxic but in some cases can be essential to use nephrotoxic e.g co-morbidity or long term renoprotective benefit e.g ACEi/ARB
Monitor RF and toxicity
In end stage renal failure- no further renal function damage can occur or decline- so not worried about nephrotoxic drugs but do need to monitor for toxic accumulation levels and side effects from this
What should occur in obese or severely underweight patients when calculating CrCl?
Use IBW for obese patients if BMI is over 30
If ABW is smaller than IBW, use ABW
What should occur if a patient has got a borderline CrCl?
Need to look at trends of their renal function- if its increasing can possible go for one above
Antibiotics- normally treat with higher dose to treat infection
What are the 3 classifications (causes) of renal disease?
Pre-renal (before the kidneys)
Intrinsic damage (damage to kidney itself)
Post-renal (after the kidneys in the urinary tract)
What is pre-renal failure?
Reduced renal perfusion, lack of blood supply to the kidney
Name and describe examples of causes of pre-renal failure:
Hypovolaemia (burns, dehydration, haemorrhage)
Decreased CO- due to HF,MI, so decreased blood flow to kidneys
Infection
Liver disease- chronic- lack of blood flow through the liver so lack of blood supply ongoing to the kidneys
Medications- ACEi, NSAIDs, ciclosporin, tacrolimus, diuretics, laxative abuse, D&V SEs
Describe the physiological state of the afferent arteriole in the glomerulus:
PGs dilate the afferent arteriole to glomerular capillaries and increase blood supply to them
Can leave the Bowman’s capsule and cause increased hydrostatic pressure and GFR to get blood into the nephron
Describe the physiological state of the efferent arterioles in the glomerulus:
Angiotensin II constricts the efferent arteriole
Hard for blood in the capillaries to get out
Describe the state of the afferent arterioles when NSAIDs are present:
NSAIDs inhibit PGs so they constrict the afferent arteriole
Potential kidney damage, decreases renal perfusion
Decrease hydrostatic pressure and GFR
Describe the state of the efferent arterioles when ACEi/ARBs are present?
ACEi/ARBs inhibit RAS so dilate the efferent arteriole
Renoprotective long term as preventing damage from high pressure
What is intrinsic renal failure?
Damage to renal tissue
Can be 2º from pre-renal failure and prolonged decreased perfusion
Name and describe examples of causes of intrinsic renal failure?
Glomerular (e.g diabetic nephropathy, glomerulonephritis- immune mediated insults)
Tubular (e.g interstitial nephritis, acute tubular necrosis)
Renovascular (e.g hypertension)
Infection
Nephrotoxicity-NSAIDs
Metabolic (e.g hypercalcamia, hyperuricaemia)
Congenital
What is acute tubular necrosis?
Necrosis of the kidney tissue from lack of perfusion and oxygen delivery
What are two ways how nephrotoxicity can occur?
Hypersensitivity reactions (unpredictable)
Directly toxic (more predictable)
Describe hypersensitivity reactions of drugs causing nephrotoxicity:
Glomerulonephritis- phenytoin, penicillins
Interstitial damage- penicillins, cephalosporin, allopurinol, azathioprine