Liver, Gall Bladder and Pancreas

Question 1

How is the chyme secreted from the stomach corrected in the duodenum?

Answer 1

1. Acidity is corrected by the addition of HCO3- from pancreas, liver and duodenal mucosa
2. Hypertonicity is corrected by the osmotic movement of water across the duodenal wall
3. Partial digestion -> completion by bile acids from the liver, and enzymes from the pancreas and duodenal mucosa.

Question 2

Where is bile secreted from?

Answer 2

Liver

Question 3

What are the constituents of bile? what cells are they secreted from?

Answer 3

Bile acid dependent:

• bile acids or bile salts: cholic acid/chenodeoxycholic acid
• cholesterol
• bile pigment esp. bilirubin
• secreted from cells lining canaliculi

Bile acid indepedent:

• HCO3-
• secreted from cells lining intra-hepatic bile ducts

Question 4

How are bile acids secreted?

Answer 4

Stomach empties causing duodenum to release CCK.

CCK causes gall bladder contraction and release of bile acids, which together with pancreatic enzymes and HCO3- from pancreas and liver (secreted under the influence of secretin) enter the duodenum via the ampulla of Vater

Question 5

How are bile acids recovered via the entero-hepatic circulation?

Answer 5

Either unconjugated by gut bacteria and are lost - replaced by hepatocytes

or

reabsorbed by epithelium in the terminal ileum into gut venous blood which joins the hepatic portal blood which enters the liver via the hepatic portal veins. in the liver, heaptocytes take bile acids up and resecrete them into canaliculi which flow into biliary ducts into the gall bladder for storage for secretion with the next time the stomach empties and CCK is secreted by teh duodenum.

Question 6

How can the storage of bile salts lead to the formation of gallstones?

Answer 6

Bile salts are secreted by canaliculi inbetween meals, well before they are needed so they are stored in the gallbladder.

To reduce storage volume, they are stored in a concentrated form, which increases the risk of percipitation and formation of gall stones.

Question 7

Gallstones are usually asymptomatic. When do they pose clinical problems? What can worsen these symtpoms?

Answer 7

When they move to the neck of gall bladder or biliary tree. here, they can cause

1) painful biliary colic
2) obstruction

both of which can cause cholecystitis (inflammation)

eating -> increase in pain (due to release of CCK -> gall bladder contraction)

Question 8

What is biliary colic?

Answer 8

Biliary colic is the term used to describe a type of pain related to the gallbladder that occurs when a gallstone transiently obstructs the cystic duct and the gallbladder contracts. Pain is the most common presenting symptom. It is usually described as sharp right upper quadrant pain that radiates to the right shoulder, or less commonly, retrosternal. Nausea and vomiting can be associated with biliary colic. Individuals may also present with pain that is induced following a fatty meal and the symptom of indigestion. The pain often lasts longer than 30 minutes, up to a few hours.

Question 9

What are the exocrine secretions of the pancreas?

Answer 9

HCO3-
Proteases - carboxypeptidases, trypsinogen, chymotrypsin and elastase
Amylases
Lipases

Question 10

What are the exocrine secretions of the pancreas? From what cells are each secreted?

Answer 10

HCO3- from duct cells

proteases - chymotrypsin, trypsinogen, elastase, carboxypeptidase, amylases and lipases by acinar cells

Question 11

What is the mechanism of HCO3- secretion from pancreatic duct cells

Answer 11

BL membrane:

1. NA-K-ATPase sets up Na concentration gradient
2. which is used to export H+ out of the cell via the BL membrane
3. In the ECF, H+ combines with HCO3- to give water and CO2
4. CO2 diffuses into duct cell via BL membrane where it recombines with water to give H+ and HCO3-

Luminal membrane - HCO3- diffuses out of cell into lumen

Question 12

how is HCO3- secretion from pancreatic duct cells controlled?

Answer 12

Secretin.

Jejunum detects low pH -> secretes secretin -> causes pancreatic duct cells to secrete HCO3-

secretin secretion is also facilitated by CCK release from the duodenum

Question 13

What stimulates pancreatic enzymes release?

Answer 13

gastric emptying -> duodenum -> increase in tonicity and fats -> CCK release from APUD cells -> pancreatic acinar cells -> enzyme release (+gall bladder contraction -> bile)

Question 14

What cells is CCK released from?

Answer 14

APUD cells in duodenum

Question 15

What is the mechanism for the digestion of fats?

Answer 15

Fats are relatively insoluble so tend to aggregate and form large globules - difficult for enzymes to effectively digest them. Acid of stomach further aggravates this.

Bile salts allow micelles to form, making fats more soluble and increase surface area on which lipases can work.

Micelles carry fats to unstirred layer next to the mucosa of the small intestine. Here, fatty acids are released and taken up by epithelial cells.

In epithelial cells, they are re-converted back into TAGs and are expelled from the cells as chylomicrons to be transported around the lymphatic system.

Question 16

What are the two functions of bile salts?

Answer 16

1) Make fatty acids more soluble

2) Increase surface area of fatty acids on which lipases can act effectively

Question 17

How is steatorrhoea caused?

Answer 17

1. insufficient lipase secretion from pancreatic acinar cells
2. insufficient bile acid secretion from liver/gall bladder

leading to presence of fat in stools -> pale, floating stools

Question 18

What are the physical innate defences of the GI tract?

Answer 18

1. Sight/smell
2. memory - if you remember that it tastes bad, you wont eat it
3. saliva - alkaline, lactoperoxidase, lysozymes, complement, polymorphs (leukocytes), IgA
4. small intestine secretions - bile, proteolytic enzymes, nutrient deprived environment, shedding of epithelial cells
5. small bowel and colon - anaerobic environment
6. colonic mucous - protcts epithelium
   gut motility - 12-18 hours, segmentation and peristalsis

Question 19

What happens if gut motility transit time increases?

Answer 19

Increased risk of infection

Question 20

What are the cellular innate defences of the GI tract?

Answer 20

1. neutrophils
2. mast cells
3. NK cells - kill viral infected cells
4. eosinophils - parasitic infections
5. macrophages - kupffer cells in the liver

Question 21

How can a GI infection causing mast cell activation cause severe fluid loss?

Answer 21

mast cells activated (antigen bind IgE) -> mass mast cell degranulation -> histmaine -> increased vascular permeability and vasodilation -> fluid loss

Question 22

What are the adaptive GI defences?

Answer 22

1. t lymphocytes - effective against intracellular organisms
2. b lymphocytes - IgA and IgE - effective against extracellular organisms
3. lymphoid tissue - GALT

Question 23

Where is GALT present? GALT infections?

Answer 23

1. Tonsils - tonsilitis
2. peyer’s patches - ileocecal lymphatic tissue infected by adenovirus -> mesenteric adenitis
3. appendicitis - inflammation at base of appendix -> blockage -> stasis -> infection, purulent in cases of chickenpox, can also be caused by faecocolith or worm infeciton -> obstruction

Question 24

What is mesenteric adenitis caused by? Where is the pain? What is it commonly mistaken for?

Answer 24

Mesenteric adenitis - infection of the ileocecal lymphatic tissue - caused by adenovirus - pain in RIF - commonly mistaken for appendicitis in children

Question 25

what organisms are resistant to GI tract defences, mainly stomach acid?

Answer 25

Mycobacterium TB H. pylori (produces urease -> protective ammonia cloud) - 13C urea breath test - breathe out 13C = urease present in stomach Enteroviruses: polio, coxsackie and hep A

Question 26

Xerostomia - complications

Answer 26

illness/dehydration -> reduced or absent saliva production - microbial overgrowth in oral and dental cavities - especially staph A -> parotitis

Question 27

Achylordia - complications

Answer 27

Reduced or absent stomach acid production due to: 1. pernicious anaemia 2. drugs such as H2 antagonists and PPIs Achlorydia increases the risk of infections with shigellosis, cholera, salmonella and C.diff in hospitals

Question 28

What type of bug is Staph A? How can we treat it?

Answer 28

Gram positive Treat with cephalosporins, carbapenems - meropenem and glycopeptides - vancomycin

Question 29

what can cause gut ischameia? And can result of gut ischaemia?

Answer 29

Intestinal venous thrombosis, arterial disease, and systemic hypotension can lead to gut ischaemia which leads to overwhelming sepsis and death

Question 30

Why does liver failure cause increase in hepatic encelopathy?

Answer 30

Ammonia is produced by gut bacteria and the deamination of amino acids. Liver failure results in failure of the urea cycle -> build up of ammonia causing hepatic encephalopathy

Question 31

How does cirrhosis lead to oesophageal varices, caput medusa and haemarrhoids?

Answer 31

Cirrhosis leads to portal venous hypertension which leads to portosystemic shunting. This shunting causes oesophageal varices, caput medusa and haemarrhoids.

Question 32

What chemicals does the liver deal with?

Answer 32

Bile pigments - main constituent: bilirubin from breakdown of Hb - conjugated in liver with glucoronide and sulphates - and secreted in bile -> excretion in faeces Enzyme breakdown - insulin Drugs Toxins Alcohol

Question 33

How is alcohol metabolised?

Answer 33

alcohol -> acetaldehyde by alcohol dehydrogenase acetaldehyde -> acetate by acetaldehyde dehydrogenase Process uses NAD+ and ATP to produce NADH and Acetyl CoA

Question 34

What are the consequences of chronic alcoholism?

Answer 34

Acetaldehyde is toxic to liver -> liver damage low NAD+ : 1. can't convert lactate into pyruvate - lactic acidosis 2. kidneys are less able to excrete uric acid -> builds up in tissues -> gout 3. failure to activate gluconeogenesis due to decrease lactate use, low NAD+ and low glycerol (low NAD+ affects glycerol metabolism) -> fasting hyperglycaemia low NAD+ and high Acetyl-CoA: fatty liver - NAD+ needed for beta oxidation of FA, without, you get increased FA synthesis and ketone bodies production. FAs get converted into TAGs but lack of LDLs means that they're not effectively transported so build up in the liver -> fatty liver. Increase ketone bodies production also leads to keto-acidosis

Question 35

What 4 blood proteins does the liver handle?

Answer 35

1. amino acids - synthesis via transamination 2. thrombopoietin - regulates platelet production in bone marrow 3. coagulation factors: fibrinogen (I), prothrombin (II), V, VII, IX, X, XI and protein S, protein C and antithrombin 4. albumin - most abundant plasma protein that controls oncotic pressure

Question 36

When is jaundice clinically detected?

Answer 36

Bilirubin levels twice the upper limit of normal i.e. >40micromols

Question 37

How does pre-hepatic jaundice come about?

Answer 37

Increased haemolysis - too much bilirubin for liver to handle and conjugate

Question 38

What are the congenital/inherited causes of pre-hepatic jaundice

Answer 38

1. Gilbert's syndrome - reduced action of bilirubin conjugating enzyme: glucronyltransferase 2. RBC membrane defects - sickle cell, hereditary spherocytosis/elliptocytosis 3. Hb defect 4. Metabolic defects

Question 39

What are the acquired causes of pre-hepatic jaundice?

Answer 39

1. immune and infection 2. mechanical - RBCs over prosthetic heart valves - lysis 3. drugs 4. burns

Question 40

What are the 5 lab findings of pre-hepatic jaundice?

Answer 40

1. decreased haptoglobin - haptoglobin binds free Hb thats released from RBCs - transports to spleen for removal - too much Hb in blood means a decreased level of free haptoglobin 2. unconjugated hyperbilirubinaemia 3. anaemia 4. increased LDH 5. reticulocytosis

Question 41

What gives rise to hepatic jaundice?

Answer 41

Liver damage - liver is less able to secrete conjugated bilirubin

Question 42

Causes of hepatic jaundice?

Answer 42

1. Congenital - wilson's (copper overload), gilbert's 2. hepatitis - viral (Hep A/B/C/E, EBV), alcohol, autoimmune, haemochromatosis (iron overload), wilson's hepatitis 3. malignancy - hepatocellular adenocarcinoma or mets 4. drugs - paracetamol 5. cirrhosis - alcohol, non-alcoholic - metabolic disorders, DM and obesity

Question 43

What are the 3 lab findings of hepatic jaundice?

Answer 43

1. elevated ASTs/ALTs 2. unconjugated and conjugate hyperbilirubinaemia 3. abnormal clotting

Question 44

What gives rise to post-hepatic jaundice?

Answer 44

intrahepatic causes hepatitis, drugs, cirrhosis, primary biliary colic extrahepatic causes - carcinoma of the bile duct, pancreatic duct, liver mets, porta hepatis lymph nodes, of the ampulla of Vater - gallstones - pancreatitis - sclerosing choleangitis

Question 45

What are the 4 lab findings of post-hepatic jaundice?

Answer 45

1. dark urine - urobilinogen 2. raised ALPs 3. normal AST/ALTs 4. conjugated bilirubinaemia

Question 46

What clinical problems can alcohol give rise to in the liver?

Answer 46

1. alcoholic hepatitis - inflammation of hepatocytes 2. fatty liver - reduced NAD+ -> FA synthesis occurs instead of oxidation (break down) - FA -> TAGs - low LDLs so not transported, and stored in liver 3. cirrhosis - fibrosis and nodular formation following liver cell necrosis and regneration

Question 47

What occurs to blood flow in a cirrhotic liver?

Answer 47

Increase resistance to blood flow

Question 48

what is wernicke korsakoff's syndrome?

Answer 48

alcohol affects thiamine absorption in GI tract, and affects thiamine storage in liver -> thiamine deficiency -> encephalopathy and fucked up brain btw encephalopathy -> confusion and dementia

Question 49

what is palmar erythema? what condition can you get it in?

Answer 49

reddening of skin, usually over the hypothenar eminence - you get it in cirrhosis/liver disease in general due to abnormal oestradiol levels -> oestradiol causes increased vascularity

Question 50

What are the signs of liver cirrhosis?

Answer 50

Palmar erythema, anaemia, jaundice, bruising, dupuytren's contractures

Question 51

What are dupuytren's contractures? what condition does it occur in?

Answer 51

occurs in cirrhosis/ liver disease - flexion contracture due to thickening and scarring of fascia covering the tendons in the hand affecting hte little and ring finger most - unknown pathophysiology

Question 52

How would you investigate cirrhosis?

Answer 52

- raised ALTs/ASTs - raised bilirubin - deranged clotting - raised ALPs - hypoalbuminaemia

Question 53

Treatment of cirrhosis

Answer 53

1. stop drinking 2. treat complications 3. transplant

Question 54

Define portal hypertension

Answer 54

Portal venous pressure exceeding 20mmHg

Question 55

What is portal hypertension caused by

Answer 55

Obstruction to portal vein - compression or thrombosis obstruction to blood flow in liver - cirrhosis, hepatoportal sclerosism schistomatosis, sarcoidis

Question 56

What are the three consequences of portal hypertension?

Answer 56

1. ascites 2. splenomegaly 3. portosystemic shunting -> varices

Question 57

Why does ascites occur with portal hypertension

Answer 57

Increased pressure of the portal venous system causes blood to back up into the abdomen. The increased hydrostatic pressure in the lumen means that less fluid is reabsorbed into blood vessels -> fluid accumulation in abdominal cavity. Ascites can be worsened if liver damage is prominent due to resulting hypoalbuminaemia and decreased in oncotic pressure of the blood vessels.

Question 58

Why does splenomegaly occur with portal hypertension?

Answer 58

Increase BP - spleen grows in size

Question 59

Why does portosystemic shunting occur with portal hypertension?

Answer 59

portal vein makes anastomoses with systemic veins. increased pressure in portal veins causes blood to back up through the anastamoses causing a rise in blood pressure. Increased BP -> dilated veins (varices).

Question 60

What are the complications of varices?

Answer 60

They can protrude into the lumen they can ulcerate they can rupture -> haemorrhaging

Question 61

Where are the portosystemic anastamoses and the varices they cause?

Answer 61

Superior -> inferior rectal vein - rectal varices Paraumbilical vein -> small epigastric vein - caput medusae Left gastric vein -> oesophageal vein - oesophageal varcies

Question 62

What is pancreatitis?

Answer 62

inflammation of the pancreas due to pancreatic enzymes released by acini

Question 63

What are the causes of pancreatitis?

Answer 63

GET SMASHED - gallstones - obstruction of pancreatic duct or ampulla of vater - stasis -infection - ethanol - hyperstimulates pancreatic enzymes - trauma - steroids - mumps - autoimmune - scorpion bite - hyperlipidaemia - ECRP/iatrogenic - drugs

Question 64

Where can gallstones cause obstruction that would lead to pancreatitis?

Answer 64

Ampulla of vater or pancreatic duct

Question 65

How does acute pancreatitis present?

Answer 65

severe pain | oedema, haemorrhage, vomiting -> dehydration and shock

Question 66

What are the clinical findings of acute pancreatitis?

Answer 66

raised ALPs, raised bilirubin, raised amylase (pancreatic amylase released into blood), glycaemia decreased calcium

Question 67

why do you get decreased calcium in acute pancreatitis?

Answer 67

it causes percipitation of calcium in the abdomen -> less free calcium

Question 68

How does chronic pancreatitis present?

Answer 68

``` Pain hypoalbuminaemia jaundice steatorrhoea malabsortiopn -> weight loss ```

Question 69

What is the msot common type of pancreatic carcinoma and how does it present?

Answer 69

ductal adenocarcinoma - 90% of pancreatic carcinomas no symptoms at first, but then a lot of symptoms all at once - vomiting - jaundice - malabsorption - pain - DIABETES - insulin from beta cells in islets of langerhans!!!!!