Organ Pathology Flashcards
Transaminase tests
AST and ALT
Elevation = hepatic inflammation and hepatocellular injury
GGT and ALP tests
Elevation = cholestasis
Bile stasis/obstruction
Bilirubin test
Elevation = jaundice
Due to biliary obstruction or hepatocellular injury
Albumin and clotting factor tests
Abnormal = impaired synthesis by liver
Risk factors for Hepatitis C
Injecting drug use Unscreened blood and donated organs Sexual transmission Mother to baby Occupational Tattoos
Hepatitis C treatment
Used to be interferon based. Suboptimal cure rates, problematic side effects, long duration
Now, direct acting antivirals taken as short course of tablets with better cure rates
Portal hypertension
High pressure in portal vein
Difficult for blood in portal circulation to return to right heart so porto-systemic collaterals can form to try and divert blood from portal circulation back to right heart - varices formation
3 causes of portal hypertension
Pre-hepatic: portal vein thrombosis
Intra-hepatic: cirrhosis
Post-hepatic: hepatic vein thrombosis or right sided heart failure
Hepatic encephalopathy
Result of chronic liver failure Liver can't detoxify substances produced by bacterial metabolism causing ammonia build up which can pass blood brain barrier Mood and personality change Inverted sleep patterns Confusion Bizarre behaviour Drowsiness Coma
HE treatment
Lactulose
Type of laxative which seems to decrease ammonia generation by bacteria and convert it to a non-absorbable molecule
Not curative
Ascites
Fluid in peritoneum causing abdominal distension
Caused by portal hypertension among other things
Increased hydrostatic pressure, decreased oncotic pressure
Budd-Chiari syndrome
Acute thrombosis of hepatic veins
Outflow of blood from liver is obstructed
Liver becomes acutely congested causing hepatocellular damage
Portal hypertension occurs, ascites develops
Budd-Chiari causes
75% no obvious cause
25% tumour, pregnancy, oral contraceptive, clotting disorders
Budd-Chiari management
Portocaval shunting to divert blood flow
Anticoagulation
Diuretics
5 general responses of hepatic injury
Intracellular accumulation Cell death Inflammation Regeneration Fibrosis
Hepatic failure
Sudden massive destruction or endpoint of chronic damage
Have to lose over 80% capacity for functional loss
Signs of hepatic failure
Jaundice
Hypoalbuminaemia
Increased ammonia = HE
Cirrhosis mechanism
Activated stellate cells cause myofibroblast proliferation and fibrogenesis
Activated Kupffer cells release cytokines
Cytokines induce inflammation causing hepatocyte dysfunction and death
Fibrosis mechanism
Proliferating hepatocytes encircled by fibrosis = parenchymal nodules
Formation of these nodules disrupts architecture of liver
Shunts formed, PV and HA blood bypasses functional liver cells causing progressive fibrosis
4 consequences of portal hypertension
Ascites
Portosystemic shunts
Congestive splenomegaly
Hepatic encephalopathy
Hepatitis A
Benign, acute, mostly asymptomatic
Faecal-oral transmission
Can cause mild illness and jaundice
Hepatitis B
Chronic or acute
Blood and body fluid borne
Immune response to viral antigens on infected hepatocytes leads to liver cell damage
Drug and toxin induced liver injury
Either predictable or unpredictable hepatotoxins
Cholestasis, hepatocellular necrosis, fatty liver, fibrosis, granulomas, vascular lesions, neoplasms
Acute = likely to be paracetamol
Chronic = likely to be alcohol
Alcoholic liver disease
Changes in lipid metabolism, decreased export of lipoproteins and cell injury caused by ROS and cytokines leads to hepatic steatosis, alcoholic hepatitis and cirrhosis
Metabolic liver disease
Also known as non-alcoholic fatty liver disease
Associated with obesity and related illnesses
Initially only hepatic steatosis, then steatosis and inflammation, then cirrhosis
Haemochromatosis
Excessive accumulation of body iron deposited in liver and pancreas
Autosomal recessive
Cholestasis of sepsis
Infection, ischaemia or circulating microbial products can cause widespread inflammation stopping bile from flowing out of liver
Autoimmune cholangiopathies
Primary biliary cirrhosis (destruction of bile canaliculi) and primary sclerosing cholangitis (destruction of bile ducts)
2 types of benign liver tumour
Cavernous haemangioma
Hepatocellular adenoma
4 types of malignant liver tumour
Hepatocellular carcinoma
Hepatoblastoma
Cholangiocarcinoma
Hepatic metastases
5 causes of jaundice
Haemolysis
Gilberts syndrome
Cholestasis
Liver obstruction (internal or external)
ALP
Alkaline phosphatase
Hydrolyses phosphate groups
Found in liver, bone, intestine, placenta and some tumours
>600 units per litre considered pathological
High in gallstones and tumours
GGT
Gamma-glutamyl transferase Mostly biliary (liver) Elevated in inflammation/obstruction of biliary system, also drugs and alcohol
ALT
Alanine aminotransferase Normal concentration <45 units per litre Found mostly in hepatocyte cytosol Key for gluconeogenesis Elevated in hepatitis
AST
Aspartate transaminase
Key for gluconeogenesis
Found in hepatocyte cytosol and mitochondria
Less liver specific and shorter half life than ALT
Elevated in hepatitis
Albumin
Normal concentration 35 - 47 g/L
Found in liver
Decreases due to cirrhosis, over excretion by kidneys, illness and redistribution
Globulins
Reflect inflammation
Elevated in chronic hepatitis and cirrhosis
Prothrombin
Reflects clotting factor synthesis
Elevation due to vitamin K deficiency or liver failure
Glucose
Liver maintains fasting blood glucose
Inability to maintain glucose indicates serious disease
Enzymatic signs of scarring and declining function
Increased GGT and ALP
Increased AST/ALT ratio
Increased globulins, bilirubin, ammonia and prothrombin
Decreased albumin and glucose
CEA
Carcinoembryonic antigen
Indicates cancer or cirrhosis, hepatitis, ulcerative colitis, smoking
>20 ng/mL indicates malignant cancer
Gilberts syndrome
Bilirubin levels high, other tests normal
Worsens after illness, fasting or alcohol
Persistent mild jaundice
Normally diagnosed by making patient fast for 48 hours. If bilirubin rises to more than double normal, Gilberts assumed
Most common causes of liver failure test abnormalities
Fatty liver
Viral hepatitis
Alcohol
Haemochromatosis
Acute pancreatitis
Inflammation of the pancreas associated with acinar cell injury
Autodigestion by pancreatic enzymes
Cell injury response mediated by inflammatory cytokines
Caused by obstruction or direct injury to acinar cells
Main categories of acute pancreatitis and their most common causes
Metabolic - alcohol
Mechanical - gallstones and trauma
Vascular - shock and vasculitis
Infection - mumps
Enzyme release in acute pancreatitis and the consequences
Protesases - proteolytic destruction of acini, ducts and islets
Lipases - fat necrosis
Elastases - blood vessel destruction leading to interstitial haemorrhage
Cell injury response - inflammation, oedema, impaired blood flow, ischaemia
Pancreatic obstruction in acute pancreatitis
Mainly by gallstones and ductal concretions in alcoholics
Increased intrapancreatic ductal pressure
Accumulation of enzyme rich interstitial fluid
Fat necrosis
Oedema and inflammation leading to compromised blood flow
Primary acinar cell injury in acute pancreatitis
Secondary to viruses, drugs, trauma and ischaemia
Releases enzymes
Clinical features of acute pancreatitis
Epigastric pain
Nausea and vomiting
Fever and tachycardia
Abdominal tenderness - in rare cases ileus and shock
Diagnosis of acute pancreatitis
High white cell count
Elevated serum amylase (lipase)
CT to look for oedema, necrosis and pseudocysts
Laparotomy (rare)
Management of acute pancreatitis
Rest the pancreas and close monitoring
IV fluids
Analgesia
Complications of acute pancreatitis
Hypotension Shock Renal and respiratory failure Low calcium, hyperglycaemia and jaundice Pseuodocysts
Chronic pancreatitis
Repeated bouts of inflammation with loss of parenchyma and replacement by fibrous tissue
Often due to heavy alcohol intake causing intraductal plugs of protein and cell debris
Also previous acute pancreatitis, severe malnutrition and CFTR mutations
Atrophy of exocrine compartment but islets relatively unaffected
Clinical features of chronic pancreatitis
Repeated attacks of abdominal pain often brought on by alcohol - can be more persistent If ongoing, loss of exocrine function causing malabsoprtion, pseudocysts Diabetes mellitus (rare)
Diagnosis of chronic pancreatitis
CT Serum amylase (not entirely accurate)
Pancreatic carcinoma
Poor prognosis. Whipples procedure performed in 15-20% cases
Common in smokers, alcohol and coffee suggested but not confirmed
If in the head, invades ampulla causing biliary obstruction
If in the tail, neck or body, silent and metastatic
Clinical features of pancreatic carcinoma
Obstructive jaundice Pain Weight loss Pancreatitis Thrombophlebitis
Cholelithiasis
Gallstones
Mostly silent
Most are cholesterol based (yellow/green)
Remainder are bilirubin/calcium salts (brown/black)
Cholesterol stones
Bile supersaturated with cholesterol. Conditions favour crystal formation. Cholesterol crystals remain in gallbladder long enough for stones to form (cholestasis)
Risk factors for cholelithiasis
Increased age and female
Oral contraceptives, pregnancy, obesity, rapid weight loss
Gallbladder stasis
Family history
Risk factors for pigment stones
Chronic haemolytic syndromes
Bacterial infection of biliary tree
Clinical consequences of gallstones
Mostly asymptomatic
Cholecystitis
Biliary colic
Clinical features of cholecystitis
Right upper quadrant abdominal pain and tenderness with fever
Neutrophil leukocytosis
Elevated bilirubin, ALP and GGT
DIagnosed by ultrasound
Acute cholecystitis
Most causes precipitated by gallstones
Obstruction of neck of gallbladder or cystic duct
Chemical irritation followed by bacterial infection
Chronic cholecystitis
Long term association of gallstones and low grade inflammation
Gallbladder often contracted with thickened wall
Management of cholecystitis
Initially - can settle with conservative therapy such as IV fluids and analgesia but can require acute surgical intervention
Long term - laparoscopic cholecystectomy
Choledocholiathis
Presence of stones in the biliary tree
Can lead to biliary obstruction with colicky abdominal pain and obstructive jaundice
Cna also lead to pancreatitis and cholangitis
Carcinoma of the gallbladder
Late presentation, poor prognosis
Older, female patients
Increased with gallstoned and chronic infections
Most are adenocarcinomas, rarely squamous or mixed
Most have invaded liver by time of diagnosis
Carcinoma of extrahepatic bile duct
Uncommon adenocarcinomas that may involve the ampullary region
Often present with slowly progressive obstruction of bile duct causing jaundice, pale stools, weight loss and nausea
Polyp
Circumscribed growth or tuour which projects above surrounding mucosa
Can be neoplastic or non-neoplastic
Majority occur sporadically in the colon and increase in frequency with increasing age
Some people prone to developing large numbers of polyps due to polyposis syndromes
Non-neoplastic polyps
Result of abnormal mucosal maturation, inflammation or hyperplasia
Neoplastic polyps
Result of proliferation and dysplasia
Called adenomatous polyps
Precursors of carcinoma
Sessile
Unbranched, immobile
Pedunculated
Branched, somewhat mobile
Hyperplastic polyps
Non-neoplastic
Benign, asymptomatic, small and sessile
Juvenile polyps
Non-neoplastic
Common in children
Usually occur in rectum and present with rectal bleeding
Composed of abundant inflamed lamina propria containing cystically dilated glands
Inflammatory polyps
Non-neoplastic
Often seen in IBD and Crohns
Benign pseudopolyps
Adenomas
Neoplastic
Familial
Can be sessile or pedunculated
Classified as tubular, villous or tubulovillous
Malignant risk factors of polyps
Polyp size - the bigger the polyp, the more cells vulnerable to changes
Architecture - villous
Severity of dysplasia
FAP
Familial adenomatous polyposis syndrome
Hundreds of adenomas, first appearing in teens/early twenties
Normally develop into cancer within 10-15 years
Genetic defect in APC gene on chromosome 5
Adenoma-carcinoma sequence
Normal epithelium
—–> Loss/mutation of APC locus on chromosome 5
Hyperproliferative epithelium
—–> Loss of DNA methylation
Early adenoma
—–> Mutation of ras gene on chromosome 12
Intermediate adenoma
—–> Loss of tumour suppressor on chromosome 18
Late adenoma
—–> Loss of p53 gene on chromosome 17
Carcinoma
Colorectal carcinoma
Most are sporadic, some have underlying genetic component (hereditary non-polyposis carcinoma of the colon, HNPCC)
Younger patients tend to have FAP or ulcerative colitis
High red meat and carb intake, low vegetable intake
Can occur anywhere in colon but rare in small intestine
Can be well, moderately or poorly differentiated
Dukes staging system of colorectal carcinoma
A = tumour protrudes submucosa or muscularis externa B = tumour protrudes into serosa C = tumour protrudes through serosa into body caivty and infects nodes
TNM staging system of colorectal carcinoma
T = Extent of invasion through bowel wall N = number of lymph nodes involved M = metastatic presence
4 rare tumours of the colon
Carcinoid - endocrine cell tumours
Lymphoma - primary blood cancer causes secondary bowel cancer
Anorectal - dominated by squamous cell carcinomas
Mesenchymal - gastrointestinal stromal tumours and lipomas
Courvoisiers sign
Palpable gallbladder
Often present in cases of prolonged biliary obstruction
Cystic fibrosis in pancreatic disease
Decreased function of CFTR gene prevents Cl- secretion. To neutralise, Na+ and H2O stay inside cell
Secretions are sticky and clog passages causing decreased lung function and increased susceptibility to lung infection
Cl- accumulates in ductal cells in the pancreas. Same thing happens here causing sticky mucus, blocked passages and blocked enzymes
Diarrhoea
> 200 g/day
Loose consistency, frequent
Acute diarrhoea
Up to 14 days
Infection (viruses most common)
Can cause inflammatory, omsotic or secretory diarrhoea
Chronic diarrhoea
More than 14 days
Inflammatory, osmotic, secretory or fatty
Campylobacter diarrhoea
Inflammatory
Acute
Caused mucosal inflammation causing increased exudate
Giardia diarrhoea
Osmotic
Acute
Mild villous atrophy leads to carbohydrate malabsoprtion
Undigested sugars are osmotically active which draws fluid in
Enterotoxigenic E. coli diarrhoea
Secretory
Acute
Toxins stimulate excessive fluid secretion
Chronic inflammatory diarrhoea causes
IBD
Diverticulitis
Small intestinal bacterial overgrowth causing direct inflammation of enterocytes
Chronic osmotic diarrhoea causes
Carbohydrate malabsoprtion
Coeliac
Small intestinal bacterial overgrowth causing malabsorption of osmotically active by-products of bacteria metabolism
Laxative abuse
Chronic secretory diarrhoea causes
Terminal ileal resection causing bile acid malabsorption
Chloecystectomy causing continuous bile flow into the small intestine
IBD
Diverticulitis
Small intestinal bacterial overgrowth causing unabsorbed food products and bile acids to stimulate secretory colon cells
Disordered motility
Laxative abuse
Chronic fatty diarrhoea causes
Pancreatic exocrine insufficiency
Bile acid malabsorption
Small intestinal bacterial overgrowth causing deconjugation of bile acids leading to impaired micelle formation and impaired fat digestion and absorption
Coeliac
Short bowel syndrome (not enough mucosal surface)
SIBO
Small intestinal bacterial overgrowth
Excess colonic bacteria in small intestine casuing bloating, flatulence, discomfort, malabsoprtion and steatorrhoea
Predisposed by impaired motility, anatomic disorders, metabolic and immune diseases
Diarrhoea in SIBO
Inflammatory: bacteria inflames enterocytes
Osmotic: Malabsorption of osmotically active byproducts of bacteria metabolism
Secferotry: Unabsorbed food and bile stimulates secertory cells
Fatty: Deconjugated bile acids causes impaired micelle formation therefore impaired fat digestion and absoprtion
Functional gut disorders
No structural or tissue abnormality Disturbed motility Visceral hypersensivity Brain-gut dysfunction Psychosocial factors Can affect any part of the gut
Oesophageal functional gut disorders
Globus
Functional heartburn
Stomach functional gut disorders
Functional dyspepsia
Fucntional vomiting
Bowel functional gut disorders
Irritable bowel
Functional abdominal pain
IBS
Swinging bowel
Abdominal pain relieved with bowel movement
May occur after gastroenteritis
Symptoms include urgency, bloating, flatulence, fatigue, poor sleep
Alarm symptoms
If present, serious pathology should be considered Nocturnal diarrhoea or pain Rectal bleeding Anaemia and iron deficiency Weight loss Vomiting Being over 50 Family history of colon cancer
Altered gut motility in in IBS
Can increase and decrease
Exaggerated response = diarrhoea, reduced response = constipation
Visceral hypersensitivity in IBS
Sufferers tend to perceive distension more than normal and describe it as painful or unpleasant rather than just uncomfortable
Peripheral sensitisation in visceral hypersensitivity
Symptoms sometimes start after an episode of gastroenteritis. Previous tissue inflammation or injury may upregulate sensitivity and excitability of nociceptors leading to hyperalgesia and allodynia
Central sensitisation in visceral hypersensitivity
Peripheral sensitisation may lead to surrounding uninjured tissue to become hypersensitive as well leading to global sensitisation throughout the body
Gate control theory
Spinal cord has a method of controlling pain signals. Hypervigilance of gate control can lead to brain focusing on processing unpleasant stimuli
Tends to increase with stress
Treatment of IBS
Multidisciplinary approach Conventional treatments (laxatives, fibre supplements, TCAs and anti-motility drugs) with dietary exclusions, probiotics and psychological therapies
Ulcerative colitis pathology
Continuous in the colon, begins in the rectum and spreads proximally
Diffuse and granular mucosal inflammation but doesn’t involve other gut layers
Rarely macroscopic ulceration
Ulcerative colitis histology
Mucosal inflammation Crypt branching and atrophy Crypt abscess Loss of goblet cells Paneth cell metaplasia
Ulcerative colitis clinical signs
Bloody diarrhoea
Frequent and urgent bowel movements
Abdominal discomfort
Fever, malaise, weight loss
Toxic megacolon
Progressive dilation causing muscular paralysis which decreases peristalsis - can lead to perforation
Crohns pathology
Can be in any part of the GI tract but most commonly the colon and ileum
Discontinuous skip lesions
Transmural inflammation
Transmural inflammation
Common in Crohns
Starts as small ulcers on mucosa and progresses to deep penetrating ulcers with fissuring, showing a cobblestone appearance
Crohns histology
Transmural inflammation across the entire depth of the intestine wall
Non-caseating and non-necrotising granulomas
Granuloma
Activated macrophages fuse together to make a giant cell which can group together in an area of inflammation
4 clinical subtypes of Crohns
Inflammatory
Structuring
Fistulising
Perianal
Inflammatory Crohns
Colitis - bloody diarrhoea
Ileitis - abdominal pain, malabsorption leading to watery or fatty diarrhoea
Gastritis and duodenitis - dyspepsia
Stricturing Crohns
Initially inflammatory due to oedema but becomes fibrotic due to scarring
Causes abdominal pain and distension, vomiting and decreased bowel movements
Fistulising Crohns
Inflammation penetrates gut wall and goes through adventitia or serosa. Becomes sticky and moves into wall of neighbouring tissue
Can be enterocutaneous, enteroenteric, enterocolic or rectovaginal
Perianal Crohns
Perianal fistulas occur which can get infected and become perianal abscesses
Anal fissures
General treatment of IBD
5-ASAs
Steroids
Immunosuppression
Monoclonal antibodies
Surgery in IBD
Colectomy can cure ulcerative colitis and help Crohns but no definitive treatment for Crohns
Can treat complications such as bowl obstruction, perforation, fistula, abscess
Genetics of Coeliac disease
Incomplete dominance
Two susceptibility genes: HLA-DQ2 and HLA-DQ8
HLA-DQ2.5 carriers will get coeliac
HLA-DQ2.2 carriers might get coeliac
HLA-DQ8 carriers generally need another allele to get coeliac
Populations without HLA-DQ2 (e.g. Asian populations) don’t get coeliac disease
Pathology of Coeliac disease
Gluten exposure required
Villous atrophy and crypt hypertrophy
Loss of brush border enzymes and loss of stimulus for pancreatic and bile secretion
Coeliac antibodies
Anti-TTG IgA mucosal antibodies for treatment
Some sufferers have IgA deficiency therefore IgG form of antibodies needed instead
Diagnosed with a combination of blood test for tissue transglutaminase antibody and biopsy to check for villous atrophy
