Hepatic & Renal Impairment Flashcards
What is the biggest cause of liver disease is the UK
Alcohol abuse
Women are more suspceptiable than men
What are the percentage blood supplies to the liver
30% from hepatic artery
70% from portal vein (brings nutrients from gut)
What does the liver do.
It has many function related to synthesis storage and degradation
Hepatocytes absorb nutrients from the gut
What nutrients the liver deal with
Carbohydrates are turned to glucose
Glucose that is not used is turned to glycogen to be stored
(Drug glucagon turns glycogen to glucose)
Vitamins and minerals (iron and B12)
Bile is made by the liver and dissolves fat soluble vitamins ADE and K
What makes up bile
Bile salts
Bilirubin
Cholesterol
Electrolytes
Water
What is the path bile takes from liver
Intrahepatic canaliculi
Hepatic duct
Gall bladder
Duodenum
What can obstructive jaundice suggest
Carcinoma of pancreas blocking the hepatic duct
What role does the liver play in immunity
Synthesis of vitamin K dependant coagulation factors which are essential for normal coagulation
Synthesis of plasma proteins (albumin - determines blood osmotic pressure, binds circulating drugs)
Contains lots of macrophage-lineage cells (kuppfer cells) (kill bacteria that have crossed the gut wall.
This is why liver damage affects ability to fight infection
What role does the liver play in hormone metabolism
Normal vitamin D metabolism
Synthesis of 25-hydroxycholecalciferol which undergoes 1-hydroxylation in the kidneys to form the active 1,25-dihydroxycholecalciferol.
This means chronic vitamin D deficiency has profound detrimental effects on bone metabolism nd health.
The liver affects sex hormones so men with chronic liver disease would have feminisation (gyno & testicular atrophy)
How does the liver contribute to drug metabolism
Lipid soluble drugs are converted into pharmacologically inactive hydrophilic metabolites to be secreted by the kidneys
Phase 1 reactions bio transform by introducing or unmasking -OH or -NH2:
Cytochrome p-450 enzymes oxidise drugs
Reduction or hydrolysis reactions.
(Enzyme variation alters metabolism rate)
Phase 2 reactions
Involve conjugation of a drug or phase one metabolite
Paracetamol at the recommended dose undergoes phase 2 reaction (glucuronidation and sulphation) and is safely secreted by kidneys
Paracetamol at overdose is oxidised when the glutathione runs out to form a toxic and harmful metabolite (causing liver necrosis and helatocyte damage)
What causes liver impairment and failure
Alcohol induced cirrhosis
Viral hepatitis
Congenital (heredity haemochromatosis - inappropriate deposition of iron leading to impaired organ function
Wilson’s disease - deposition of copper
a1-antitrypsin deficiency - liver cirrhosis and lung destruction)
Acquired disorders can affect - the bile ducts, parenchymal helatocytes, blood vessels
What are common disorders of the bile ducts
Gallstones
Inflammation and fibrosis
Primary biliary cirrhosis (liver disease characterised by destruction of the small bile ducts).
Primary sclerosing cholangitis - inflammation within ducts
Hepatitis - inflammation of the liver
What is cirrhosis
Abnormality of the liver, regeneration of abnormal fibrotic cells incompatible with normal liver function.
Statistics for liver cancer
Hepatocelluar carcinoma
The liver is also a common place for metastatic deposition
The risk of development depends on liver health such as chronic hepatic infection, aflatoxin schistosomiasis, alcohol abuse
Portal hypotension
Rise in pressure here will cause a large effect on liver functions with adverse effects on other organs
This hypotension can cause gastro oesophageal varices (opening of these large veins) causing this to happen in oesophagus leading to haemorrhage.
What is splenomegaly
Venous connections between liver and spleen enlarge meaning spleen is engorged with blood and swells increasing risk of anaemia and prolonged bleeding
What are clinical features of acute liver failure
Jaundice
Abdominal pain
Swollen belly
Nausea vomiting
Malaise
Can be induced by improper prescription of drugs
Can be induced by improper self medication
Clinical features of liver impairment/failure
Could induce this with improper prescription
Self medicating patients may induce this
Jaundice most common sign
Prolonged bleeding (bruising easily)
Hepatorenal syndrome (chronic liver impairment can induce renal failure resulting in poor clearance of metabolites)
Malnutrition and fluid overload ascites
reduced hepatic synthesis of albumin leads to tissue oedema
Nail changes
Altered hormone metabolism - gyno decrease in body hair, testicular atrophy male impotence
How is liver function managed and monitored
Liver function tests “LFTs” simple blood test to measure
Bilirubin (normal upper limit of 19mmol)
Alkaline phosphotase (raised with duct obstruction or pathology)
Alkaline transferase (raised in liver damage)
Albumin (reduced in chronic liver damage)
Prothrombin time (clotting time (INR) this is influenced by synthesis of coagulation factors)
Biopsy
Imaging
Drugs to be avoided/prescribed with precaution
Aspirin
NSAIDs
Opioids
Paracetamol
Erythromycin
Flucloxacillin
Metronidazole
Tetracyclines (antibiotics)
Fluconazole, Miconazole and similar
Lidocaine (be aware of IV administration)
What is Reye’s syndrome
This is induced in children who are given aspirin
Viral infection followed by adverse drug reaction to aspirin
Vomiting
Drowsiness
Irritability
Confusion
Irrational behaviour
Convulsions and coma
Mortality very high
Facts about liver transplant
Liver failure is indexation for transplant be that through alcohol abuse or hepatitis
Adult donor liver may be split in two for transplantation
Part of a liver can be taken from liver donor
Immunosuppressants needed for life
80% graft survival after one year
How should liver issue patients be managed in practice
Risk assessment to calculate
Cause of disease
Known or unknown blood borne disease
Problems with prolonged bleeding
Past, current or planned treatment
Awareness that oral manifestations may occur from anaemia
Increased risk of infection and poorer wound healing
Oral dryness may suggest secondary sjogrens
What does RRT stand for and mean
Renal replacement therapy
Dialysis or transplantation
What does ESRF stand for and mean
End stage renal failure
Renal function has demonised to such a point that RRT is needed to sustain life
What is renal impairment
She function has diminished but not to ESRF yet
What do the kidneys do
Secrete waste products and retain certain minerals needed
The secrete urea and creatinine, as function decrease these increase
They receive 20% of cardiac output
They balance pH
Produce erythropoietin which up regulates the production of red blood cells
Produce renin which stimulates release of angiotensin 1
Essential for normal vit D metabolism and bone turnover (vit D undergoes 1-hydroxylation in kidneys to create 1,25-dihydroiycholecalciferol) promoting calcium absorption from intestine)
Reduced vit D causes raised phosphate levels and increases parathyroid hormone
What causes renal impairment and failure
Diabetes Mellitus (diabetic nephropathy)
Hypertension (hypotensive nephropathy)
Autosomal dominant polycystic kidney disease
Alports syndrome
Renovascular disease
Systemic lupus erythematosis
HIV
Cancers
Drugs
Clinical features of renal impairment and failure
Acute renal failure (presents with oliguria less that 40pml a day, retention of urea and creatinine loss of electrolyte balance)
Chronic renal failure
Coagulation abnormalities
Cardiovascular disease
Renal oateodystrophy
Malnutrition
Oedema
Immune impairment
Increased risk of malignancy
Sexual dysfunction mental illness
How is renal disease diagnosed and managed
U&Es
Meuse urea, creatinine and electrolytes in venous blood
Urine volumes
Biopsy
Imaging
Prescribing in renal impairment
Avoid or use with caution
Aspirin
NSAIDs
Opioids
Cillin derived drugs (penicillin, amoxicillin)
Cefalexin
Flucloxicillin
Tetracyclines
Fluconazole
Acyclovir
How renal impaired patients advised to manage it
Low protein diet
Hypotension management
Dyslipidaemia management
Dialysis
Transplant (immunosuppressed patients more likely to develop malignancy)
