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Phase 2a Sheffield Medicine > Liver > Flashcards

Liver Flashcards

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1
Q

What are the 4 functions of the Liver?

A
  1. Glucose and fat metabolism
  2. Detoxification and excretion
  3. Protein synthesis e.g. albumin and clotting factors
  4. Defence against infection
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2
Q

Where is most of the blood supplied to from the liver?

A

The portal vein.

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3
Q

What are the 3 Liver function tests?

A
  1. Serum bilirubin
  2. Serum albumin
  3. Pro-thrombin time
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4
Q

What are the 4 fat soluble vitamins?

A

ADEK

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5
Q

Give an example of a transamine?

A

AST and ALT

They increase in hepatocellular disease

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6
Q

When does Alkaline phosphatase increase in the serum?

A

In cholestatic (duct and obstructive) disease.

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7
Q

What is budd chiari syndrome?

A

Vascular disease associated with occlusion of hepatic veins

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8
Q

What are some pathological changes in the liver associated with excessive alcohol consumption?

A
  1. Fatty liver
  2. Alcoholic hepatitis
  3. Cirrhosis
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9
Q

What condition is associated with the liver and oedema?

A

Hypoalbuminaemia

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10
Q

What are the causes of haemolytic anaemia?

A
  1. Sickle cell disease
  2. Hereditary spherocytosis
  3. GP6D Deficiency
  4. Hypersplenism
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11
Q

What is ascites?

A

An accumulation of fluid in the peritoneal cavity that leads to abdominal extension

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12
Q

What are the signs of ascites?

A
  • Flank swelling

- Dull to percuss and shifting dullness

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13
Q

What are the pathological causes of Ascites?

A
  1. Local inflammation e.g. peritonitis
  2. Leaky vessels e.g. imbalance between hydrostatic and oncotic pressures
  3. Low flow e.g. cirrhosis, thrombosis and heart failure
  4. Low protein e.g. hypalbuminaemia
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14
Q

What are the physiological factors that contribute to ascites?

A
  • High portal venous pressure

- Low serum albumin

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15
Q

Describe the pathogenesis of ascites

A
  1. Increased intrahepatic resistance causes portal hypertension –> Ascites
  2. Systemic vasodilation leads to RAAS, NAd and ADH secretion –> Fluid retention
  3. Low serum albumin also causes ascites
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16
Q

What investigation would you use in ascites?

A
  • Ultrasound

- Ascitic tap – important to rule out bacterial peritonitis

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17
Q

What would be the management of ascites?

A
  • Fluid and salt restriction
  • Diuretics – spironolactone
  • Large volume paracentesis and albumin
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18
Q

What are the two different types of ascites?

A

Exudative ascites

Transudative ascites

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19
Q

What are Exudative ascites?

A

Increased vasc permeability to infection; inflammation or malignancy

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20
Q

What are transudative ascites?

A

Increased venous pressure due to cirrhosis, cardiac failure or hypoalbuminaemia

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21
Q

If neutrophils are present in ascites, what is this indicative of?

A

Spontaneous bacterial peritonitis

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22
Q

What is chronic liver disease?

A

A wide range of conditions affecting the liver characterised by disease of over 6 months and progressive destruction of the liver.

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23
Q

What are the causes of Chronic liver disease?

A
  1. Alcohol
  2. Non-Alcoholic fatty liver disease (NAFLD)
  3. Viral Hep (B,C,E)
  4. AI diseases
  5. Metabolic e.g. haemochromatosis
  6. Vascular e.g. budd-chiari
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24
Q

What are the signs of chronic liver disease?

A
  1. Ascites
  2. Oedema
  3. Malaise
  4. Anorexia
  5. Bruising
  6. Itching
  7. Clubbing
  8. Palmar erythema
  9. Spider naevi
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25
What are the outcomes of chronic liver disease?
1. Cirrhosis | 2. Liver failure
26
What is the management of chronic liver disease?
Dependent on the cause - Steroids, interferon, antivirals - Supportive therapy for complications – Albumin, vit K, diuretics - Possible transplant
27
What should you ask a patient with expected drug induced liver injury?
If they are on any medications or have began taking any new medications recently.
28
What are drugs that can cause induced liver injury?
- Co-amoxiclav - Flucloxacillin - Erythromycin - TB drugs
29
What are drugs that do not cause induced liver injury?
1. Low dose aspirin 2. NSAIDs 3. Beta blockers 4. HRT 5. CCB
30
What is Glutathione Transferase?
Mops up reactive intermediate of paracetamol and thus prevents toxicity and liver failure.
31
What 4 features would you see in a paracetamol overdose?
1. Metabolic acidosis 2. Prolonged thrombin time 3. Raised creatine (renal failure) 4. Raised ALT
32
What is the treatment for paracetamol overdose?
IV N-Acetyl-cysteine
33
What are the symptoms of acute liver disease?
- Malaise - Lethargy - Anorexia - Jaundice
34
What are the causes of acute liver disease?
1. Viral hepatitis 2. Drug induced hepatitis 3. Alcohol induced hepatitis 4. Vascular 5. Obstruction
35
What are the outcomes of acute liver disease?
1. Recovery | 2. Liver failure
36
What are the investigations in acute liver disease?
Blood test - prothrombin response time.
37
What are the treatments in acute liver disease?
Dependent on the cause
38
What is hepatitis?
Inflammatory condition of the liver
39
How long must hepatitis be present for it to become chronic?
6 months or more.
40
What are the symptoms of acute hepatitis?
1. General malaise 2. Myalgia – pain 3. GI upset 4. Abdo pain 5. Raised AST,ALT 6. Possible jaundice
41
What are the causes of acute hepatitis?
1. Viral e.g. A,B,C,D,E 2. Drug induced 3. Alcohol Induced 4. Autoimmune
42
How long does HBsAg be present in the serum post infection?
6-18 weeks.
43
When could you detect Anti-HBV core (IgM)
Rises from 6 weeks and peaks at 18.
44
How can you tell if a patient has been vaccinated or previously been accepted?
If they have anti-HBV's IgC in their serum.
45
What are the infective causes of acute hepatitis?
1. Hepatitis A to E infection 2. EBV 3. CMV 4. Toxoplasmosis
46
What are the non infective causes of acute and chronic hepatitis?
1. Alcohol 2. Drugs 3. Toxins 4. Autoimmune
47
What are the infective causes of chronic hepatitis?
- Hep B +-D - Hep C - Hep E
48
What are the complications of chronic hepatitis?
Uncontrolled inflammation --> Fibrosis --> Cirrhosis --> HCC
49
Is Hep A a DNA virus or RNA virus?
RNA virus
50
How can Hep A virus be prevented?
Vaccination
51
How is Hep A transmitted?
Faeco-orally e.g. contaminated food and water
52
How can you diagnose Hep A?
Viral serology initally --> anti-HAV IgM then Anti-HAV IgG
53
What is the management of Hep A?
- Supportive - Monitor liver function to ensure no fulmiant hepatic failure - Manage close contacts
54
Is Hepatitis B an RNA or DNA virus?
DNA virus which replicates in hepatocytes
55
How is Hep B transmitted?
Blood borne --> needle stick injury.
56
How many cases of Hep B go onto chronic infection?
5%
57
What is the natural history of Hepatitis B?
1. Immune tolerance phase --> unimpeded viral replication --> High HBV DNA levels 2. Immune clearance phase --> IS wakes up, liver inflammation and high ALT 3. Inactive HBV Carrier phase --> HBV DNA low, No inflammation and normal ALT 4. Reactivation Phase --> ALT and HBV, DNA levels are intermittent and inflame is seen on liver due to fibrosis
58
What does HBV Trigger in the immune system?
Core proteins
59
How would you diagnose HBV?
Viral serology --> HBV surface antigen from 6th week to 18th week or anti-HBV core IgM after 3 months.
60
How would you manage Hepatitis B?
1. Supportive 2. Liver function monitoring 3. Manage contacts 4. Follow up at 6 months to see if HBV surface Ag has cleared --> if present chronic hepatitis
61
How could you tell if someone has a chronic HBV?
A follow up appointment in 6 months to see if HBV surface antigen had cleared.
62
What are the consequences of chronic HBV infection?
1. Cirrhosis 2. HCC 3. Decompensated cirrhosis
63
How can HBV infection be prevented?
Vaccination - inactivated HbsAg
64
What is the treatment for HBV?
- Alpha interferon- boosts immune system | - Antivirals e.g. tenofovir --> inhibit viral replications
65
What are the side effects of alpha interferon?
Myalgia, malaise, lethargy, thyroiditis, mental health issues
66
Is Hepatitis C a RNA or DNA virus?
Blood borne RNA Virus
67
How much of Hep C passes on to be a chronic infection?
70%
68
What are the risk factors for HBV/HCV
1. IVDU 2. People who have required blood results 3. Needles stick injuries 4. Unprotected sex 5. Materno-foetal transmission
69
How would you diagnose HCV?
Viral serology - presence of Anti-HCV and IgM/IgC RNA.
70
How can you prevent HCV?
1. Screen blood products 2. Lifestyle modification 3. Needle exchange
71
Does HCV infection confer immunity?
No. There is no vaccine either.
72
What is the current treatment for HCV?
Direct acting antivirals e.g. NS5A and NS5B
73
Is Hep D an RNA virus or DNA virus?
RNA virus
74
What does Hep D require to survive?
Hep B infection as it is protected by HbsAg
75
How is Hep D caused?
Blood borne transmission
76
How do you treat Hep D?
Get rid of Hep B.
77
How is Hep E caused?
Faeco-oral RNA virus
78
When can Hep E be chronic?
In patients with compromised immune systems.
79
How would you diagnose Hepatitis E?
Viral serology for initially anti-HEV IgM then Anti-HEV IgG.
80
What is the primary prevention for Hep E?
Good food hygiene and a vaccine is in development
81
What are the symptoms of spontaneous bacterial peritonitis?
- Dull to percussion - Temp - Abdo pain
82
What are the causes of peritonitis?
- Stomach ulcer - Infection - Abdo wound/injury - Cirrhosis of liver
83
What investigations are necessary in peritonitis?
- Blood tests – raised WCC, platelets, CRP, Amylase, reduced blood count - CXR – Look for air under the diaphragm - Abdo x-ray --> bowel obstruction - CT scan – inflammation, ischaemia, cancer - ECG - Epigastric pain could be related to heart - B-HCG --> Hormone secreted by pregnant women
84
What are the complications for peritonitis?
1. Hypovolaemia 2. Kidney failure 3. Systemic sepsis 4. Paralytic ileus 5. Pulmonary atelectasis (lung collapse) 6. Portal pyaemia (pus in portal vein)
85
How can the paralytic ileus cause resp problems?
- Peristaltic Waves stop --> dilation of bowel --> distended abdo therefore increased pressure - Pushes on diaphragm --> respiration affected
86
What is the management of peritonitis?
1. ABC 2. Treat underlying cause 3. Call a surgeon 4. Set up post-management
87
What are the causes of liver failure?
1. Infection e.g. viral hep b,c 2. Induced e.g. alcohol, drug toxicity 3. Inherited e.g. autoimmune
88
What are the symptoms of liver failure?
- Jaundice - Pain in URQ - Nausea/swelling
89
What are the appropriate investigations in Liver failure?
- FCB, WCC, CRP/ESR + Prothrombin time. - CT/MRI abdo - Liver biopsy
90
What are the complications of Liver failure?
1. Hepatic encephalopathy 2. Abnormal bleeding 3. Jaundice 4. Ascites
91
What is the management of liver failure?
1. Nutrition 2. Supplements 3. Treat complications 4. Liver transplant
92
How is hepatic encephalopathy a complication of liver failure?
- Liver can’t get rid of ammonia so ammonia crosses the BBB | - Cerebral Oedema
93
Why are liver failure patients vulnerable to infection?
1. Impaired reticulo-endothelial function 2. Reduced opsonic activity 3. Leukocyte function is reduced 4. Permeable gut wall
94
What are the prehepatic causes of jaundice?
unconjugated --> haemolysis, gilberts
95
What are the hepatic causes of jaundice?
Conjugated --> Hepatitis, ischaemia, neoplasm, Drugs, cirrhosis
96
What are the post hepatic causes of jaundice?
Conjugated --> Gallstones, bile duct, malignant, ischaemic, inflame, mirizzi stricture.
97
What would the stools and urine look like in a pt with prehepatic jaundice?
Urine and stools are normal, no itching and LFT’s are normal
98
What would the stools and urine look like in a pt with cholestatic jaundice?
Dark urine and pale stools, itching and LFT’s are abnormal
99
What is raised conjugated bilirubin an indicator of?
cholestatic problem e.g. hepatic liver disease or bile duct obstruction.
100
What investigations would be neccesary in Jaundice?
- History - Urinalysis for bilirubin - LFTs
101
What is the management of Jaundice?
Manage the underlying cause.
102
What is cirrhosis of the liver?
A chronic disease of the liver resulting from necrosis of liver cells leading to fibrosis Characterised by nodular regeneration End result is impairment of hepatocyte function and distortion of liver architecture
103
How is cirrhosis of the liver caused?
1. Alcoholic 2. Hep B and C 3. Any chronic liver disease e.g. autoimmune, metabolic or vascular
104
What are the symptoms of liver cirrhosis?
- Fatigue - Easy bleeding/bruising - Jaundice and oedema - Loss of periods/sex drive - Confusion and slurred speech --> hepatic encephalopathy!
105
What investigations should you order in liver cirrhosis?
LFT INR --> blood ability to clot Biopsy Creatinine
106
What are the risk factors of liver cirrhosis?
Obesity viral hep alcohol abuse
107
What is the treatment of Liver cirrhosis?
1. Deal with underlying cause 2. Screening for HCC 3. Consider transplant
108
What is a consequence of hepatocyte regeneration in cirrhosis?
Neoplasia and thus HCC
109
What are some common serious infections in those with liver cirrhosis?
Spontaneous bacterial peritonitis Can also be caused by E.coli and S. pneumoniae Can be diagnosed through looking for the presence of neutrophils in ascitic fluid
110
What are gallstones made out of?
Cholesterol, phospholipid and bile pigment.
111
What are the risk factors of gallstones?
1. Female 2. Obese 3. Fertile
112
What are the symptoms of gallstones?
1. Pain in RUQ of abdo and centre 2. Pain in right shoulder and between shoulder blades 3. Nausea or vomiting 4. Asymptomatic
113
What are the complications of gallstones?
1. Biliary pain 2. Obstructive jaundice 3. Cholangitis (infection of biliary tract) 4. Pancreatitis
114
What investigations should be ordered in gallstones?
- Ultrasound | - ERCP
115
What is the treatment for gallstones?
- Laparoscopic cholecystectomy
116
What is cholecystitis?
Inflammation of the gallbladder caused by blockage of the bile duct --> obstruction to bile emptying
117
What are the symptoms of cholecystitis?
1. RUQ pain 2. Fever 3. Raised inflammatory markers 4. NO JAUNDICE
118
What is the cause of cholecystitis?
blockage of the bile duct causing obstruction to bile emptying.
119
What are the risk factors of cholecystitis?
Obesity and diabetes
120
What are the investigations used in diagnosing cholecystitis?
- FBC --> WCC look for infection - CRP/ESR --> inflammatory - HIDA scan - Abdo/endoscopic US
121
What is the appropriate management for cholecystitis?
- Fluids - Analgesia - ERCP procedure to remove stones. - Cholecystectomy = gallbladder removal.
122
What is ascending cholangitis?
Obstruction of biliary tract causing bacterial infection  EMERGENCY!
123
How is ascending cholangitis different from the presentation of cholecystitis?
It presents with jaundice!
124
What are the symptoms of ascending cholangitis?
Charcot’s triad 1. Fever 2. RUQ 3. Jaundice
125
What investigations would you order in suspected ascending cholangitis?
1. Ultrasound 2. Blood tests -LFT 3. ERCP – definitive investigation
126
What is the appropriate treatment of ascending cholangitis?
- IV Fluid - IV antibiotics e.g. Cefotaxime and metronidazole - ERCP to remove stone - Stenting
127
What is the pathology of sclerosing cholangitis?
- Inflammation of the bile duct  structures harden - Progressive obliterating fibrosis of bile duct branches - Leading to cirrhosis and liver failure.
128
What are the symptoms of primary sclerosing cholangitis?
1. Itching 2. Rigor 3. Pain 4. Jaundice 5. 75% have IBD
129
What condition is associated with sclerosing cholangitis?
Reynolds pentad
130
What is reynold's pentad characterised by?
- Charcot’s pentad - Hypotension - Altered mental state
131
Are most liver cancers primary or secondary?
Secondary - from the GI tract, breast and bronchus
132
What is Wernicke's encephalopathy?
An acute neurological syndrome which is caused by a lack of thiamine presenting with a triad of symptoms.
133
What is the cause of WE?
Lack of B1 seen in alcohol usage
134
What are the symptoms of WE?
1. Ataxia 2. Ophthalmoplegia 3. Confusion
135
What are the investigations of WE?
- Clinical history - MRI scan - LFTs
136
What is the treatment of WE?
IV thiamine.
137
What is alcohol liver disease associated with?
Macrocytic anaemia.
138
What would be seen on a biopsy in alcohol liver disease?
Lots of mallory bodies.
139
What are the symptoms of ARLD?
1. Abdo pain 2. Loss of appetite 3. Fatigue 4. Feeling sick/diarrhoea
140
What are the phases of ARLD?
1. Fatty change – hepatocytes contain triglycerides 2. Alcoholic hepatitis 3. Alcoholic Cirrhosis – destruction of liver architecture and fibrosis
141
What investigations could you order in ARLD?
- LFT - Blood test for serum albumin - Prothrombin time --> clotting factors indicates liver damage - A Good history. - Liver biopsy
142
What is the treatment for ARLD?
- STOP DRINKING - Psychological therapy to encourage stopping. - Symptom management --> corticosteroids - Liver transplant
143
What is Non-alcoholic steato-hepatitis?
An advanced form of non-alcoholic fatty liver disease
144
What are the causes of non-alcoholic steato-hepatitis?
1. T2DM 2. Hypertension 3. Obesity 4. Hyperlipidaemia
145
A 4-year-old girl presents with diarrhoea and is hypotensive. What is the physiological reason that fluid moves from the interstitium to the vascular compartment in this case?
Reduced hydrostatic pressure. Fluid will move from the interstitium into the plasma if there is an increase in osmotic pressure or a decrease in hydrostatic pressure. As this patient is hypotensive it is more likely to be the latter.
146
How is haemoglobin broken down?
1. Haem is broken down into Fe2+ and Biliverdin 2. Biliverdin reductase converts biliverdin to unconjugated bilirubin 3. Glucuronosyltransferase converts unconjugated bilirubin to conjugated in the liver. 4. Conjugated bilirubin forms urobilinogen via intestinal bacteria.
147
What is the function of glucuronosyltransferase?
Transfers glucuronic acid to unconjugated bilirubin to form conjugated bilirubin
148
Why can't unconjugated bilirubin travel in the blood without albumin?
Unconjugated bilirubin binds to albumin as it isn’t H2O soluble so needs to bind to albumin so it can travel to the blood in the liver.
149
What is the 3 things that urobilinogen can do?
1. Go back to the liver via enterohepatic system 2. Can go to the kidneys forming urinary urobilin 3. Can form stercobilin which is excreted in the faeces
150
What is diverticulitis?
Infection and inflammation of diverticula (pouches) along the digestive tract.
151
What is the epidemiology of diverticulitis?
Diverticular disease most commonly affects older patients with low fibre diets
152
What is most commonly affected in diverticulitis?
descending colon.
153
What is the pathophysiology of diverticulitis?
Outpouching of bowel mucosa --> faeces get trapped and obstruct the diverticula This causes abscess and inflammation leading to diverticulitis
154
What are the signs of diverticulitis?
- Similar to appendicitis but on the left side - Pain in left iliac fossa region, fever and tachycarida. - Diarrhoea/constipation --> rectal bleeding with blood and mucus
155
What is acute diverticulitis?
a sudden attack and swelling in the diverticula, can be due to surgery.
156
What are the causes of diverticulitis?
- Surgery (acute) | - Infection
157
What are the investigations for diverticulitis?
- Colonoscopy - CT - Bloods --> CRP for inflammation and possible WBC for infection.
158
What is the treatment for diverticulitis?
- High fibre diet - Paracetamol --> not aspirin and ibuprofen as can cause stomach upsets. - Surgery --> severe cases.
159
What are oesophageal varices?
Abnormal, enlarged veins in the oesophagus prone to bleeding.
160
What are the symptoms of varices?
1. Haematemesis 2. Melaena 3. Abdo pain 4. Dysphagia 5. Anaemia
161
What investigations would you order in varices?
- Abdo CT/Doppler US of splenic/portal veins - Capsule endoscopy - Endoscopic exam
162
What is the treatment for varices?
- Endoscopic therapy --> Banding | - Beta blockers e.g. propranolol to reduce portal hypertension.
163
What is the pathophysiology of oesophageal varices?
Obstruction to portal blood flow leads to portal hypertension Blood is diverted into collaterals e.g. gastro-oesophageal junction so causes varices
164
What is a major risk associated with oesophageal varices?
Haemorrhages if they rupture
165
What is primary biliary cirrhosis?
autoimmune disease where there is progressive lymphocyte mediated destruction of intrahepatic bile ducts --> cholestasis --> cirrhosis
166
What is the epidemiology of primary biliary cirrhosis?
- Females affected more then men | - Familial trend
167
What is the pathophysiology of primary biliary cirrhosis?
- Lymphocyte mediated attack on bile duct epithelial | - Destruction of bile ducts --> cholestasis and then cirrhosis
168
What diseases are associated with primary biliary cirrhosis?
Thyroiditis, RA, Coeliac disease, Lung disease
169
What are the symptoms of primary biliary cirrhosis?
1. Itching and dry eyes 2. Fatigue 3. Joint pains 4. Variceal bleeding
170
What would be the blood results in primary biliary cirrhosis?
- Raised IgM - Raised ALP - Positive AMA
171
What is the treatment for primary biliary cirrhosis?
Ursodeoxycholic acid --> improves liver enzymes, reduces inflame and portal pressure so reduces the rate of variceal development
172
What is biliary colic?
A gallbladder attack --> RUQ pain due to gallstone blocking the bile duct.
173
What are the symptoms of biliary colic?
- RUQ pain | - Itching – due to build-up of bilirubin
174
What are the risk factors?
Female, obese, over 40, have a condition that affects bile flow, IBD/IBS, taking ceftriaxone.
175
What is the main difference between biliary colic and acute cholecystitis
Acute cholecystitis has an inflammatory component
176
What are 3 metabolic disorders of the liver?
- Haemochromatosis – iron overload - Alpha 1 anti-trypsin deficiency - Wilsons disease – Disorder of copper metabolism
177
What is the mechanism of Alpha 1 anti-trypsin deficiency leading to chronic liver disease?
results in protein retention --> causing cirrhosis.
178
What are the general symptoms of alpha 1 anti-trypsin deficiency?
Frequent chest infection, wheezing, chronic cough, breathlessness during exercise, associated with jaundice and cirrhosis.
179
What is the treatment for Alpha 1 anti-tryspin deficiency?
Treat the conditions it causes e.g. COPD or liver cirrhosis.
180
What is wilson's disease?
- Autosomal recessive disorder of copper metabolism
181
How does wilsons disease cause hepatic failure and cirrhosis?
Excessive deposition of copper in the liver, causing hepatic failure and cirrhosis
182
What is the treatment of Wilsons disease?
- Life treatment with pencillamine
183
What are the causes of portal hypertension?
1. Cirrhosis and fibrosis (Intra-hepatic causes) 2. Portal vein thrombosis (Pre-hepatic causes) 3. Budd-chiari (post-hepatic cause)
184
What are the symptoms of portal hypertension?
1. Ascites 2. GI Bleeding --> black tarry stool 3. Reduced level of platelets 4. Hepatic encephalopathy
185
What investigations would you order in portal hypertension?
- Endoscopic - Splenomegaly - Ultrasound - Patient history - Bloods --> clotting factors (prothrombin)
186
What are the complications of portal hypertension?
- Splenomegaly | - Varices
187
What is the treatment for portal hypertension?
- Propanolol --> prevention of bleeding and varicies --> reduces portal pressure.
188
What are the causes of duct obstruction?
1. Gallstones 2. Stricture (narrowing) e.g. malignant, inflammatory 3. Carcinoma 4. Blocked stent
189
What are the symptoms of duct obstruction?
- Abdo pain in RUQ - Dark urine - Fever - Jaundice
190
What investigations are neccesary in duct obstruction?
- Abdo CT and US - ERCP - Blood tests --> alkaline phosphatase, liver enzymes and bilirubin level.
191
What is the treatment of duct obstruction?
- Dependent on the cause --> stop the blockage
192
What are the complications of duct obstruction?
sepsis, liver disease, biliary cirrhosis.
193
What is haemochromatosis?
Inherited condition --> iron overload.
194
What histological stain would you use to test for haemochromatosis?
Perl's stain
195
What is the cause of haemochromatosis?
90% of people have a mutation in the HFE gene --> Autosomal recessive inheritance
196
What is the protein, controlling iron absorption, which is lacking in Haemochromatosis called?
Hepcidin
197
What are the symptoms of haemochromatosis?
1. Hepatomegaly 2. Cardiomegaly 3. Diabetes mellitus 4. Hyperpigmentation of skin 5. Lethargy
198
What is the pathophysiology of haemochromatosis?
Uncontrolled intestinal iron absorption leads to deposition in heart, liver and pancreas --> fibrosis --> organ failure
199
What is an indicator for the diagnosis of haemochromatosis?
- Raised ferritin - HFE Genotyping - Liver biopsy
200
What are the causes of iron overload?
1. Genetic disorders e.g. haemochromatosis 2. Multiple blood transfusions 3. Haemolysis 4. Alcoholic liver disease
201
What is druggability?
the ability of a protein target to bind with molecules with high affinity.
202
What are 4 drug targets?
- Receptors - Enzymes - Transporters - Ion channels
203
What is a receptor?
a component of a cell that interacts with a specific ligand --> can be exogenous (drug) or endogenous (hormones)
204
How can cells communicate?
- Neurotransmitters --> Acetylcholine - Autacoids – cytokines - Hormones – testosterone
205
Give 4 types of receptors.
- Ligand gated ion channels (nicotinic ACh receptor) - G protein coupled receptors (Beta adrenoceptors) - Kinase-linked receptors (Growth factors) - Nuclear receptors (steroid receptors)
206
Describe ligand gated ion channels
- Binding causes transformational protein change to allow ion through.
207
Describe G protein coupled receptors
- GPCR are a group (7) of receptors in the eukaryotic membrane. - G proteins (GTPases) act as molecular switches - When activated it transduces a signal.
208
Describe kinase-linked receptors
- Transmembrane receptors are activated when binding of EC ligand - This causes enzymatic activity on IC side.
209
Describe nuclear receptors
- IC receptors, modify gene transcription, causing a conformational change - This causes Zinc fingers in which can bind to the genome --> switching on transcription.
210
Define affinity
how well a drug binds to a receptor Agonists --> high affinity and efficacy
211
Define efficacy
how well a ligand activates to a receptor and induces a conformational change. Antagonists --> high affinity but no efficacy

Phase 2a Sheffield Medicine (10 decks)

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