Deck 5 Flashcards
Pancreatisis causes
Idiopathic gallstones (lodged at sphincter of oddi) alcohol (increases zymogen secretion and decreases fluid and bicarb, causing obstruction) Trauma Steroids Mumps Autoimmune Spider/scorpion bite Hypercalcaemia/hypertriglyceridaemia ERCP Drugs (azathioprine, furosemide, immunosuppressants, thiazides, ACEi, NSAIDs, sulphonamides)
Pancreatitis general
Can range from mild to severe. 20% are mild and resolve spontaneously.
Males affected more than females. Gallstones and alcohol are biggest causes
Pancreatitis S+S
N&V, epigastric pain, radiating to back, relieves on sitting forward.
Cullen’s sign
Grey turner sign
Hypercalcaemia (due to fat necrosis)
Signs of sepsis (tachycardia, fever, rigid abdomen, shock)
ileus
Pancreatitis investigations
Amylase, lipase (more specific and better after initial phase when amylase decreases), bone profile (hypercalaemia), triglycerides, FBC, U&E, CRP, ABG, lactate and o2
Clinical diagnosis, imaging not needed but may do: AXR to show ileus CXR to exclude other cause USS to exclude gallstones CT abdo if uncertainty MRCP to visualise ductal system
Scoring system for pancreatitis
Glasgow scoring system P (aO2<8) Age (>55) Neutrophils/WCC>15 Calcium <2mmol Renal, urea (>16) Enzymes (LDH >600, AST>200) Albumin (<32) Sugar (glucose >10) 3 or more is severe -HDU/ITU
Can also use Apache II (clinical features, age and comorbidities to give score. >9 is severe)
Randon criteria uses age, lab score on admission and38h to give mortality risk
periductal pancreatitis
Necrosis of acinar cells adjacent to duct- obstruction cause
panlobular pancreatitis
whole acinar lobule necrosis. Drugs, toxins, viruses, metbolic insult
Perilobular pancreatitis
necrosis of peripheries. shock/hypothermia
Pancreatitis management
Fluids (3rd space loss), analgesia (caution with morphine, can spasm sphincter of oddi), NG tube, adeqaute oxygenation, ERCP if gallstones, broad spec Abx
Pancreatitis complications
Pancreatitis necrosis (liquifactive haemorrhagic necrosis), pseudocyst (can be infected and form abscess), abscess formation (pain, anorexia, palpable tender mass - CT visible) Can also lead to hypovolaemic shock (blood vessels rupture), , DIC, ARDS (inflammation causes leaky blood vessels), thrombosis of splenic/gastroduodenal arteries (bowel necrosis), hyperglycaemia, hypokalaemia, hypoalbuminaemia, vitamin deficiency
Primary haemostasis
Platelet mediated.
Injury causes vasoconstriction to allow platelet adhesion to exposed collagen.
VWF binds collagen, Gp2b on platelets bind vWF.
Platelets release ADP/TXA2
Collagen activated platelets expose fibrinogen receptors.
Soft, weak plug formed
Primary haemostasis impairment
Bruising, epistaxis, gum bleeding, menorrhagia, intra/immediate post op bleed
Primary haemostasis impairment cauaes
Thrombocytopoenia, lack of GP1b (Bernard Soullier syndrome), lack of GP2b/a (Glanzmann’s thrombasthaenia), antiplatelet drugs, VWF impairment
Thrombocytopoeania causes
Overuse (septicaemia, DIC, TTP), immune reaction (autoimmune, drug induced), decreased production (alcohol, cytotoxic drugs, bone marrow failure), hyperplenism
Aspirin/NSAIDs block`
COX1 (TXA2), but also COX2
Clopidogrel/tricagrelor block
ADP binding P2Y12
Abciximab/eptifibatide block
Gp2b3b
Secondary haemostasis
Clotting cascade and fibrin mesh (needs tissue factor).
Vitamin K dependent clotting factors
2,7,9,10
Extrinsic pathway
Activation of VII and X
Use PT to measure.
INR is PT corrected - normal is 0.9-1.1
Intrinsic pathway
12->11->9–>8 and 10
APTT meausres.
Measure for unfractionated heparin
APTT
Intrinsic pathway
Symptoms of secondary haemostasis disorder
Haemarthrosis, muscular/soft tissue bleed, extensive bruising, delayed post op bleed/poor wound healing
Causes of secondary haemostasis disorder
Reduced coagulation factors (congenital is haemophilias, acquired through warfarin, liver dysfunction, DIC)
To investigate primary haemostasis disorders
FBC (platelet number), blood film (morphology), platelet function test, vWF assays (specialist
To investigate secondary haemostasis
Clotting screen:
- PT time (extrinsic. Needs tissue factor and calcium. Prolonged is VII issue)
APTT (intrinsic. Add kalolin, phospholipid and calcium. Prolonged is VIII, IX, XI or XII).
If prolonged APTT then mixing stud used to see if correctable factor deficiency or inhibitory protein.
Can also look at D dimers/fibrinogen degredation products, or individual clotting factor (specialist).
Prolonged PT and APTT`
Likely mixed clotting deficiency, but rarely can be II, V or X
Fibrinolysis
Plasminogen - > tPA to plasmin. Degrades fibrin (products include D dimer)
Haemophilia A
More common, larger gene.
Severity based on VIII levels.
<1% is severe, >5% is mild and can be asymptomatic
Mild may respond to desmopressin as this increases VWF in blood (and VWF carries factor VIII)
Acute hepatitis
Fever, nausea, arthalgia, jaundice, develops over several days.
Typical pre-icteric phase beforehand - often has cigarette smoke aversion and RUQ pain.
Hepatocytes swell, then necrose (esp zone 3 as less blood)
Jaundice, pale stoole and dark urine as intrahepatic cholestatic jaundice. Get pruritus and rash
Hep A
A is faeco-oral. 2-6 week incubation. Notifiable disease. 80% asymptomatic. Not chronic. No specific treatment. Typically affects age extremes.
Hep B
B is in blood/semen/saliva. But vertical transmission is most common worldwide. 1-6 month incubation. Has core antigen (HBcAg) and surface (HBsAg). 10% of those infected get chronic disease, 1% get fulminant disease. Only DNA Hepatitis.
HEP B markers
○ HBsAg shows at 6 weeks, but disappears by 3 months
○ HBsAB marks previous cleared infection or vaccination
○ HBeAg shows infectivity (viral replication)
○ HBeAb is natural immunity marker
○ HBcAb IgG is non specific marker of infection (current/previous)
○ HBcAbIgM marks infection within last 6 months
○ HBVPCR is best viraemia marker
Summary is that surface antigen shows recent infection. No core antibody is vaccination only. Lack of HBeAb can be chronic infection.
Hep C
C causes chronic infection, transmitted in body fluids. V common in IVDU. Vertical and sexual transmission uncommon. 85% become chronic, 30% get cirrhosis in 20 years. No vaccine.
Hep D
D is dependent on B. Can be acquired simultaneously, but subsequent hep D infection has worse outcome.
Hep E
Hep E is feco-oral. Similar picture to hep A. More common in indo-china. Can cause severe disease in pregnant women. No vaccine?
Other viral hepatitis
CMV, yellow fever, HSV in immunocompromise
Bacterial hepatitis causes
Leptospirosis, Q fever, syphilis
Parasitic hepatitis causes
malaria
Non infective hepatisis
○ Autoimmune
○ Alcoholic (shows fatty changes, necrosis, ballooned cells and hyaline deposits)
○ NAFLD
○ Toxins
○ Metabolic (haemochromatosis, Wilson’s)
Drug induced (paracetamol, aspirin, diclofenac, co-amox)
Hepatitis classed as hepatic or cholestatic or steatosis
Hepatocellular (AST/ALT rise), or cholestatic(bilirubin/ALP/GGT rise)
Histologically, if inflammatory change then hepatitis, if bile block then cholestasis and fatty is steatosis
Chronic hepatitis
Last longer than 6 months. Can be HepB/C/D but also autoimmune
Autoimmune hepatitis may present
Jaundice, fatigue, deranged LFTs, urticaria, polyarthritis, glomerulonephritis, amenorrhoea
Cirrhosis
Fibrosis, loss of normal architecture and nodule development. Kupffer cells and hepatocytes cause fibrosis, stellate cells become myoofibroblasts and secrete collagen
Micronodular disease
<3mm - tends to be alcoholic liver damage or biliary tract disease
Macronodular
> 3mm, tends to be previous hepatitis
Cirrhosis S+S
Fatigue, Hx of liver disease, weight loss, anorexia, ascites, jaundice, peripheral oedema, bleeding/bruising, pruritis (tx with cholestyramine), leukonychia, palmar erythema, clubbing, liver flap, duyputren’s contracture, pigmentation, spider nevi, striae, portal HTN signs,
Cirrhosis causes
Hep B and C, Alcoholism, NAFLD, haemochromatosis, wilson’s, PBC, PSC, autoimmune hepatitis, Drugs (e.g. amiodarone)
Cirrhosis complications
hypoproteinuria (ascites and odema)
oesophageal varices
Secondary hyperaldosteronism (hypoalbuminaemia and portal HTN cause renal hypoperfusion - hepatorenal syndrome
Ascites (portal HTN, low protein and salt/water ret - Transudate)
Hepatic encephalopathy (ammonia, glutamine, use lactulose)
Venous distension (haemorrhages, paraumbilical vein, osesophageal varices)
Cirrhosis decompensation
Can be stable, but deterioration can occur in:
- Dehydration
- Constipation (ammonia builds up in bowel)
- Alcohol binge
- Sepsis (spontaneous bacterial peritonitis)
- Excessive opioid use (metabolised in liver, also gives constipation)
GI bleed (extra protein in bowel - > ammonia production)
Portal HTN varices
Varices at left gastric vein (gastric/oesophageal varices), rectal vein, retroperitoneal organs, paraumbilical
Portal HTN causes
Pre hepatic (portal vein thrombosis), hepatic(cirrhosis/hepatitis), post hepatic (Budd Chairi syndrome - hepatic veins obstructed).
PBC
Primary biliary cirrhosis.
Autoimmnune against small/medium IH ducts.
normally AMA positive
More females>males.
40s and 50s
FHx and IBD association
T cell mediated, leads to bile and salt retention, hepatocyte injury and cirrhosis
Increased HCC risk
Tx by slowing progression with ursodeoxycholic acid
S+S
See fatigue, pruritus, hypercholesterolaemia (+/- skin hyperpigmentation, xanthalasma, steatorrhoea, vit D malabsorption). In advanced disease, splenomegaly, jaundice.
PSC
Primary sclerosing cholangitis
Affects large intrahepatic ducts and extrahepatic ducts - although small ducts can be impacted by cholestasis.
Oedema and inflammation narrow lumen and cause strictures.
Cholestsis and fibrosis give cirrhosis.
Increased risk of cholangiocarcinoma
More males affected (30s)
Symptoms: fatigue, pruritus, jaundice, ascending cholangitis, chronic pancreatitis, chronic cholecystitis.
Associated with UC (screen by raised ALP)
May have pANCA or ANA (AMA negative)
Difference between PBC and PSC
PBC tends to be older, tends to be female, associated with sjogren, thyroid, scleroderma. Often AMA or ANA. PBC is radiologically normal. PBC is loss of small ducts
PSC is younger, more male, associated with IBD, often ANCA but may be ANA (AMA negative), PSC has strictures and beading of large bile ducts and pruning of smaller ducts. PSC is inflammatory desctruction of extra and intraheptic ducts, fibrotic obliteration of small ducts
Cholesterol supersaturation
Pregnancy, hypercholesterolaemia, CoC, depleted bile acids (terminal ileum disease/resection), bile stasis (fasting, TPN), increase Hb breakdown (spherycytosis, sickle cell, malaria, mech heart valves
Stones most likely to be radioopaque
Pigmented
Cholelithasis
Stones in gallbladder
Choledocholithiasis
Stones in bile duct
Cholestasis
Bile flow block
Biliary colic
RUQ sudden pain, typically radiates to R shoulder. Lasts <6h as stone falls back. Normal normal O/E, apyrexial but may have N&V
Stones on USS.
Analgesia and cholecystectomy within 6 weeks
Cholecystitis
Stone in hartman’s pouch or cystic duct, causes chemical irritation from bile. May have superimposed infection
Constant RUQ pain, N&V, lethargy, tachycardia, no jaundice.
Murphey’s sign
Analgesia, IVAbx and fluid, cholecystectomy within 1 week
Chronic cholecystitis
Fibrosis and thickening but not distension
choledocholithiasis
Stone impacted in common bile duct. May cause obstructive jaundice. Can predispose to pancreatitis or ascending cholangitis
Mirizzi’s syndrome
Cholelithiasis causes external compression of common hepatic duct, gives obstructive jaundice but no dilatation of cystic/common bile duct
Cholangitis
Inflammation of biliary tree. Obstruction and infection.
Charcot’s triad (RUQ pain, fever and jaundice). Peristent pain, pyrexia with rigors. May have pruritus, pale stool and dark urine. Sepsis risk.
Needs blood cultures.
ERCP is diagnostic and treatment
Carcot’s triad
Cholangitis symptoms. Fever, RUQ pain and jaundice
Gallbladder imaging
USS good for stones, can measure gallbladder thickness and duct dilatation. Pericholecystic fluid shows inflammation
MRCP is MRI. Diagnostic onlh. Visualises biliary tree
ERCP is GSTD for cholangitis. Ideally MRCP first to visualise. Pancreatitis risk
T tube. not recommended now, used after bile duct exploration to prevent CBD blockage through swelling
Courvoisier’s sign
patient with painless jaundice and enlarged gallbladder has malignancy until proven otherwise.
Hepatobiliary cancer types
90% secondaries (GI, lung - esp SCLC, breast), 10% primaries (most of these are HCC, but can get cholangiocarcinomas)
Most pancreatic cancers are ductal
Clinical features of hepatobiliary tumours
RUQ pain, weight loss, nausea, fever, jaundice and liver fiailure symptoms
Liver biopsy CI
prolonged PT, platelet count <80, ascites, extra hepatic cholestasis
Primary liver cancer RF
Chronic hep B, hep C, alcoholic liver disease, metabolic disease, PBC, NAFLD
primary liver cancer tumour marker
alpha fetoprotein. Correlates to tumour size and poor prognostic marker
cholangiocarcinoma
presentation
In part of biliary tree (including hepatic). Generally adenocarcinoma.
Presents as per bile duct obstruction (RU! pain, pruritus, dark urine, pale stool)
Cholangiocarinoma RF and management
PSC, anatomical liver abnormality (cyst or congenital issue), obesity, diabetes, hepolithasis (chronic hepatic stones), liver fluke, hep B and C
Can resect caudate lobe. Can stent bile duct for palliative relief
Pancreatic cancer
Nearly always adenocarcinoma (exocrine endothelial cells, but can get acinar and cystoadenocarcinoma
Pancreatic cancer RG
- Smoking
- Obesity
- Diabetes (although may be cause)
- Alcohol
- Chronic pancreatitis
60+
Presentation of pancreatic cancer
2/3s are head of pancreas. Compresses CBD and presents late with painless obstructive jaundice. Progresses to ascites, anaemia, fatigue and nausea
1/3 body/tail. Causes vague B symptoms and nausea. Ascites late feature. May have incessant epigastric pain (relieved on sitting forward)
Pancreatic cancer complications
T3c diabetes, pancreatic exocrine insufficiency (steaorrhoea, malnutrition), DVT/PE
Islet cell tumour
Rare, associated with MEN syndrome
-isletoma causes hypoglycaemia and weight gain
Glucoagonoma causes secondary diabetes
Gastrinoma causes Zollinger ellison syndrome
Somatostatinoma causes diabetes, achlorrydia, gallstones
VIPoma causes profound diarrhoea
Benign liver tumours
Haemangiomas, can be incidental finding on CT/USS. Tx if >5cm
LFT analysis
ALT>AST in most liver injury, but AST2:ALT1 then alcohol (esp if raised GGT)
10xAST/ALT raise is hepatocellular picture
ALP/GGT 3x raise is cholestasis
Isolated ALP in bone disease and pregnancy
Bilirubin cycle
Unconjugated to conjugated, then urobilinogen and either stercobilin (stool) or urobilin (or recycled)
Prehaptic jaundice causes
Normal urine, normal stool.
Severe malaria, Pernicious anaemia, sickle cell anaemia, thalasaemia, transfusion reactions, autoimmuen (e.g. SLE), Gilbert’s syndrome
Hepatic causes of jaundice
Dark urine, slightly pale stool.
Hepatitis (esp A) liver tumours, alcoholic hepatitis, drug introduced (NSAIDs, antiepileptic, antibiotics), autoimmune, Wilson’s disease
Post hepatic
Pale stools, dark urine
Gallstone, cholangiocarcinoma, strictures, pancreatic cancer, PSC, abdominal mass (lymphoma)
Jaundice investigations
Blood film/coombs if ?haemolytic jaundice
Macrocytic anaemia in haemolytic anaemia and liver disease
Viral serology/autoantibodies (?hepatitis)
MRCP (non invasive, high res)
CT/MRI to assess itnrahepatic/pancreatic lesions
Biopsy (if clotting ok)
ERCP if ductal system dilated, or percutaneous transhepatic cholangiography if ERCP not possible. Can stent but can’t view ampulla or pancreatic duct)
Spleen basics
White pulp (B and T cells screen blood), red pulp (filters out old RBCs and stores 1/3 of platelets. asplenic people need lifelong abx (phenoxymethylpenicllin)
Splenomegaly causes
Increased demand (removing RBc, extramedullary haematopoesis, infection (EBV/HIV)
Infiltration (leukaemia, lymphoma, haematoma, cyst, IE, sepsis)
Inflammation (RA, SLE, sarcoidosis)
Abnormal blood flow (e.g. portal/hepatic vein obstriction, hepatic schistomiasis)
Autoimmune haemolytic anaemia
Do Coombs test
90% are warm
If IgG alone then warm AIHA or drug induced
If complement alone then can be cold
If IgG plus complement then warm, mixed warm and cold or drug induced (methyldopa)
Can also be seen in SLE, chronic inflammatory disesae
Splenomegaly sequaelae
Any splenomegaly can cause hypersplenism with panctopoenia, increased plasma volume and haemolysis
