GIM 3 Flashcards
What organs does the portal vein supply the liver from?
Stomach, spleen, intestine, pancreass
Where do bile pigments (e.g. bilirubin) originate from?
Breakdown products of haemoglobin conjugated with glucuronic acid
What is urobilinogen and how is it secreted?
Bile pigments acted on by colon bacteria.
Some taken back into blood and excreted by kidney as urobilin (yellow pigment of urine).
Some converted into stercobilin (brown pigment of faeces)
How is bile directed to storage in the gall bladder?
Hepatocytes secretions build up pressure and bile flow is forced towards the duodenum. Flow into duodenum is prevented by closure of Sphincter of Oddi and enters gall bladder instead.
What happens to bile during storage in the gall bladder?
Bile salts and pigments concentrated due to salt and water reabsorption in gall bladder
How does bile enter the duodenum after a meal?
Neural influences and CCK relaxes Sphincter of Oddi and contracts gall bladder
What are gall stones?
Cholesterol crystallisation from bile salts
How is the liver related to metabolism of carbohydrates?
Converts fructose and galactose to glucose
Converts some glucose to glycogen for storage
Converts some glucose to triacylglycerol
What does the liver do to absorbed fats?
Combines fats with protein and released as lipoproteins
What are the 2 phases of liver detoxification?
Phase 1 - oxidation/reduction
Phase 2 - conjugation
What causes jaundice?
Bilirubin accumulation in plasma.
What are the signs and symptoms of jaundice?
Yellowing of skin, sclera and mucous membranes. May produce kernicterus - deposits of pigment in brain leading to nerve degeneration
How do you treat jaundice?
Light - breaks down pigment
What are the different types of jaundice?
Haemolytic jaundice - excessive haemolysis of red blood cells
Intrahepatic jaundice - defect in uptake, conjugation or secretion of bilirubin by hepatic cells
Obstructive jaundice - blockage of bile ducts
Physiological jaundice of newborn - babies have poor capacity for conjugating bilirubin
What is hepatitis?
Infection/inflammation of the liver (acute or chronic)
What is cirrhosis?
Necrosis of liver cells - replaced by fibroblasts
What are the pacemaker cells of the gut called?
Interstitial cells of Cajal. Initiate basal electrical rhythm
How does parasympathetic activation increase gut motility?
Acetylcholine acts on muscarinic receptors
How does sympathetic activation decrease gut motility?
Directly - noradrenaline on beta-adrenoceptors
Indirectly - noradrenaline on alpha2-adrenoceptors decreases release of ACh
How is peristalsis initiated?
Mechanoreceptors in pharynx detect food bolus. Persitaltic wave initiated and controlled by vagus nerve.
What is the purpose of peristaltic waves in the stomach?
To mix gastric contents and to empty contents into duodenum.
What is vasoactive intestinal polypeptide (VIP)?
Peptide hormone responsible for peristaltic relaxation. Stimulated by oesophageal and gastric distension.
What slows the rate of gastric emptying into the duodenum?
Osmolarities of chyme greater and smaller than 200 mOsm
Excess acid in the small intestine
Fat in upper small intestine
What increases the rate of gastric emptying into the duodenum?
Greater volume of gastric contents
Smaller fragment size
What is the purpose of segmenting contractions in the small intestine? What muscle type does it occur in?
To mix intestinal contents with secretions and increase exposure to mucosal surface. Circular muscle.
How do contractions ensure food moves oral to anal?
Basal electrical rhythm in duodenum is 12/min and 9/min in terminal ileum
How is small intestine motility controlled?
Myogenic mechanisms (stretch)
Myenteric plexus (local regulation)
Extrinsic nerves
Local chemicals
Describe large intestinal motility
Mostly slow and non-propulsive with 3/4 powerful contractions per day for defecation
What is cholestasis?
When bile cannot flow from liver to duodenum.
Why are bilirubin levels used in a liver function test?
Liver conjugates bilirubin to make it water soluble and excretes it as bile. High levels of bilirubin mean liver function impaired. Increased in cholestasis, hepatocellular damage and haemolysis.
What are the aminotransferases used in liver function tests and why are they useful for testing liver function?
Aspartate (AST) and alanine (ALT) transaminase. Leak out from damaged cells so markedly raised in hepatocellular damage
Why is alkaline phosphates used in liver function tests?
Present in canalicular and sinusoidal membranes of liver and markedly raised in cholestasis and metastatic infiltration of the liver
Why is international normalised ratio (INR) used in a liver function test?
Uses prothrombin time to show coagulation activity. High INR shows liver damage (blood is taking longer to clot)
What is bilirubin in the urine and pale stools a sign of?
Obstructive jaundice - liver can convert bilirubin to soluble form but cannot excrete it in bile
What are goblet cells?
Exocrine glands that secrete mucus
What are enteroendocrine cells?
Cells of the GI tract that produce hormones and have paracrine, neurocrine and endocrine effects
What is the epithelium type in the stomach?
Gastric columnar mucosa
What does the pKa of a drug tell us?
The pH at which the ratio when the drug is charged:uncharged is 50:50
Are weak acid or weak base drugs more likely to enter brain
Weak base drugs because they are largely present in unionized form at blood pH
Why is drug ionisation related to absorption?
Drugs that are ionised cannot pass into cells as they cannot get across the lipid bilayer. Unionised drugs can diffuse into the cells.
What is found in the portal field in the liver?
Portal vein
Hepatic artery
Bile duct
Lymphatic vessels
What is a liver sinusoid?
Highly porous vascular channel derived from fusion of terminal branches of hepatic artery and portal vein
What are liver canaliculi?
Intercellular gutters between hepatocytes
What are the three concepts of organisation inside the liver?
Classic lobule - drained by central vein
Portal lobule - drained by bile duct
Acinus - supplied by terminal branches of hepatic artery and portal vein
What are Kupffer cells?
Resident macrophages in the liver
What are hepatic stellate cells?
Store 80% of the body’s retinol (vit A) and produce the EDM scaffold that holds the space of Dissé open
What is the space of Dissé?
The space between a hepatocyte and a sinusoid containing blood plasma
What are peribiliary glands?
Secrete mucin, stem cell niche, contribute to regeneration of biliary epithelium after injury
What are the two types of gland in the pancreas?
Exocrine glands Endocrine glands (islets of Langerhans)
What are the clinical features of viral hepatitis?
Malaise Anorexia Nausea Abdominal discomfort Fever Pale stool/dark urine Jaundice
Describe the makeup of hepatitis A
+ve single stranded RNA
How is hepatitis A transmitted
Faecal-oral transmission (contaminated food or water)
What are the consequences of hepatitis A infection?
Asymptomatic infection Acute icteric (jaundice) hepatitis
How is hepatitis B transmitted?
Mother to baby
Sexual
Parenteral (unsafe injections, transfusion)
What is the main transmission of hepatitis C?
Blood-borne virus
What is emesis?
Vomiting
What are the different types of anti-emetic drugs that can be used?
H1-receptor antagonists - promethazine, act on vestibular nuclei to help motion sickness
Anti-muscarinic agents - hyoscine
Dopamine antagonists - metoclopramide, effective against anti-cancer drug emesis
5-HT antagonist - ondansetron, anti-cancer drugs
How do enterotoxigenic bacteria cause diarrhoea?
Adhere to brush border, increase cAMP, increased Cl- and Na+ secretion, increased water secretion
How do you treat diarrhoea?
Oral rehydration therapy - replace lost electrolytes.
How do antimotiliy agents help treat diarrhoea?
Opioid drugs that inhibit presynaptic release of ACh. Reduces GI motility and increases transit time to promote water reabsorption (codeine and loperamide)
How do laxatives treat constipation?
Through osmotic effect and by stimulating GI motility (e.g Mg2+, lactulose)
How do you treat IBS?
Antispasmodic agents (antimuscarinics to inhibit parasympathetic activity), amitriptyline (alters nerve sensitivity in GIT)
