Hepatic & Renal Impairment

Question 1

What is the biggest cause of liver disease is the UK

Answer 1

Alcohol abuse
Women are more suspceptiable than men

Question 2

What are the percentage blood supplies to the liver

Answer 2

30% from hepatic artery
70% from portal vein (brings nutrients from gut)

Question 3

What does the liver do.

Answer 3

It has many function related to synthesis storage and degradation
Hepatocytes absorb nutrients from the gut

Question 4

What nutrients the liver deal with

Answer 4

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

Question 5

What makes up bile

Answer 5

Bile salts
Bilirubin
Cholesterol
Electrolytes
Water

Question 6

What is the path bile takes from liver

Answer 6

Intrahepatic canaliculi
Hepatic duct
Gall bladder
Duodenum

Question 7

What can obstructive jaundice suggest

Answer 7

Carcinoma of pancreas blocking the hepatic duct

Question 8

What role does the liver play in immunity

Answer 8

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

Question 9

What role does the liver play in hormone metabolism

Answer 9

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)

Question 10

How does the liver contribute to drug metabolism

Answer 10

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)

Question 11

What causes liver impairment and failure

Answer 11

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

Question 12

What are common disorders of the bile ducts

Answer 12

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

Question 13

What is cirrhosis

Answer 13

Abnormality of the liver, regeneration of abnormal fibrotic cells incompatible with normal liver function.

Question 14

Statistics for liver cancer

Answer 14

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

Question 15

Portal hypotension

Answer 15

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.

Question 16

What is splenomegaly

Answer 16

Venous connections between liver and spleen enlarge meaning spleen is engorged with blood and swells increasing risk of anaemia and prolonged bleeding

Question 17

What are clinical features of acute liver failure

Answer 17

Jaundice
Abdominal pain
Swollen belly
Nausea vomiting
Malaise
Can be induced by improper prescription of drugs
Can be induced by improper self medication

Question 18

Clinical features of liver impairment/failure

Answer 18

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

Question 19

How is liver function managed and monitored

Answer 19

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

Question 20

Drugs to be avoided/prescribed with precaution

Answer 20

Aspirin
NSAIDs
Opioids
Paracetamol
Erythromycin
Flucloxacillin
Metronidazole
Tetracyclines (antibiotics)
Fluconazole, Miconazole and similar
Lidocaine (be aware of IV administration)

Question 21

What is Reye’s syndrome

Answer 21

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

Question 22

Facts about liver transplant

Answer 22

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

Question 23

How should liver issue patients be managed in practice

Answer 23

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

Question 24

What does RRT stand for and mean

Answer 24

Renal replacement therapy
Dialysis or transplantation

Question 25

What does ESRF stand for and mean

Answer 25

End stage renal failure
Renal function has demonised to such a point that RRT is needed to sustain life

Question 26

What is renal impairment

Answer 26

She function has diminished but not to ESRF yet

Question 27

What do the kidneys do

Answer 27

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

Question 28

What causes renal impairment and failure

Answer 28

Diabetes Mellitus (diabetic nephropathy)
Hypertension (hypotensive nephropathy)
Autosomal dominant polycystic kidney disease
Alports syndrome
Renovascular disease
Systemic lupus erythematosis
HIV
Cancers
Drugs

Question 29

Clinical features of renal impairment and failure

Answer 29

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

Question 30

How is renal disease diagnosed and managed

Answer 30

U&Es
Meuse urea, creatinine and electrolytes in venous blood
Urine volumes
Biopsy
Imaging

Question 31

Prescribing in renal impairment

Answer 31

Avoid or use with caution
Aspirin
NSAIDs
Opioids
Cillin derived drugs (penicillin, amoxicillin)
Cefalexin
Flucloxicillin
Tetracyclines
Fluconazole
Acyclovir

Question 32

How renal impaired patients advised to manage it

Answer 32

Low protein diet
Hypotension management
Dyslipidaemia management
Dialysis
Transplant (immunosuppressed patients more likely to develop malignancy)