Block 15 Flashcards
Definition of Cirrhosis
chronic damage → hepatocyte destruction → chronic scarring + damage tht become irreversible → liver becomes fibrotic
Which cells mediate the fibrosis process?
Stellate cells
Where are stellate cells found?
in the perisinusoidal space btwn. hepatocytes + sinusoid
Main function of stellate cells
store vitamin A
What do injured hepatocytes release that activate stellate cells?
parakrin factors
What happens to activated stellate cells?
- they lose vitamin A
- they proliferate
- they secrete TGF-beta
all of this triggers collagen production => fibrotic tissue formation
Explain the mechanism of portal hypertension
build up of fibrotic tissue compresses central vein + sinusoids → increases P in sinusoid and thus the portal veins
OR
new vessels produced in angiogenesis provide low-volume, high P venous drainage tht cannot accomodate as much blood vol as normal => portal vein P increases
Why does portal hypertension increase risk of ascites + congestive splenomegaly?
increased chance tht fluid in BVs gets pushed into tissues + across tissues into lrg open spaces e.g. peritoneal activity –> ascites
Pathological effects of decreased liver function
- ⇒ decreased detoxification ⇒ toxins can enter brain and cause hepatic encephalopathy e.g. ammonia → asterixis(hand tremor)
- decreased oestrogen metabolism ⇒ more oestrogen in blood → gynaecomastia, spider angiomata, palmar erythema
- increased unconjugated bilirubin as liver normally conjugates bilirubin ⇒ jaundice
- decreased albumin → hypoabluminaemia
- decreased clotting factor production- prolongs prothrombin time
Describe some histopathological features of cirrhosis:
- regenerating nodules
- bridging fibrosis
Why does transaminase increase in hepatitis?
damaged hepatocytes leak out amino transminase into blood which increases liver transaminase => ALT + AST will increase
Describe the general mechanism of hepatitis infection
Hep virus infects hepatocyte → CD8+ cells recognise abnormal proteins presented on MHC I → Cytotoxic killing → hepatocyte apoptosis → liver damage → increased transaminase
What are then signs + symptoms of the icteric phase of acute viral hepatitis?
- darkened urine -> conjugated bilirubin gets filtered into urine making it darker
Jaundice
Anticteric hepatitis is
hepatitis w/o jaundice
3 types of jaundice
Pre-hepatic
Intrahepatic
Post-hepatic
Pre-hepatic jaunduce
- excessive RBC breakdown
- overwhelms liver’s ability to conjugate bilirubin ⇒ unconjuagted hyperbilirubinaemia
Causes of Intrahepatic Jaundice
hepatic cell dysfunction ==> liver loses ability to conjugate bilirubin
Causes of post-hepatic jaundice
biliary drainage obstruction
e.g. gallstones, abdo masses
Definition of Jaundice
high levels of bilirubin in blood
Most common causes of jaundice
- viral hepatitis
- alcohol related liver disease
Types of hepatitis transmitted by faecal-oral route
Hep A and Hep E
Type of hepatitis transmitted by blood
Hep C and Hep B
Key marker of Hep B
HBV surface antigen HbsAg
Which Hep virus needs Hep B to infect?
Hep D
Elevated IgM in Hep A + Hep E infection indicates
active infection
How can acute hepatitis be differentiated from other causes of jaundice?
marked elevations of AST + ALT
ALT typically higher than AST
Adults at high risk of HBV infection
- Men who have sex with men
- People with a sexually transmitted infection
- People who have had > 1 sex partner during the previous 6 months
- Health care and public safety workers potentially exposed to blood or other infectious body fluids
- People who currently or have recently injected illicit drugs
- People who have diabetes and are < 60 years old (or ≥ 60 years if their risk of acquiring HBV is considered increased)
- People with end-stage renal disease who receive dialysis, HIV infection, or chronic liver disease, or hepatitis C
- Household contacts and sex partners of people who are HBsAg-positive
- Clients and staff members of institutions and nonresidential day care facilities for people with developmental disabilities
- People in correctional facilities or facilities providing services to injection-drug users
- International travelers to regions with high or intermediate HBV endemicity
4 main types of shock
Hypovolaemic - low blood volume; can be haemorrhagic or non-haemorrhagic
Cardiogenic - trauma to heart tht prevents it from pumping oxygenated blood to rest of body
Obstructive - type of cardiogenic shock can be due to obstruction of flow e.g. pulmonary embolus OR restriction of flow -> physical restriction due to fluid in pericardial sac e.g. cardiac tamponade, tension pneumothorax
Distributive - excessive vasodilation → decreases vascular resistance which decreases BP
2 types of hypovolaemic shock
Non-haemorrhagic - not from bleeding e.g. dehydration
Haemorrhagic - from bleeding e.g. due to ruptured BVs
Medical definition of shock
Failure of the circulation that results in INADEQUATE TISSUE PERFUSION
Mixed venous oxygen saturation
=> amount oxygen bound to Hb coming to R side of heart i.e the oxygen not extracted/used by tissues
Most common cause of cardiogenic shock
acute MI → muscle cells die → weaker contractility → less blood pumped out of heart
What class of shock is septic shock?
Distributive
Inheritance
Lynch syndrome is a
Autosomal dominant condition caused by mutations in DNA mismatch repair genes that increases your risk of bowel caner
Think modifiable, non-modifiable and genetics
Risk factors for bowel cancer
Non-modifiable
- older age
- male
- having IBD
Modifiable
- smoking
- eating red meat
- lack of fibre
- obesity
Genes
- familial adenomatous polyposis
- hereditary nonpolyposis (lynch syndrome)
Where do most colorectal carcinomas arise?
ADENOCARCINOMAS -> from the intestinal glands/crypts
Definition
Primary biliary cirrhosis is:
chronic disease that affects the bile ducts, leading to blockage, causing the build up of bile within the liver, causing liver inflammation and scarring
Acute cholangitis is
acute inflammation and infection of the common bile duct due to:
chronic obstruction or bacterial growth
Charcot’s triad of symptoms is
FEVER
ABDOMINAL PAIN
JAUNDICE
Reynolds pentad of symptoms:
(first 3 are the same as Charcot’s triad)
FEVER
ABDO PAIN
JAUNDICE
CONFUSION
HYPOTENSION
Embryonic origin of adrenal medulla
Neural crest ectoderm
Embryonic origin of adrenal cortex
intermediate mesoderm
Where are bile salts/acids reabsorbed?
terminal ileum
Why can removal of the terminal ileum cause diarrhoea?
because bile salts/acids cannot be reabsorbed so they enter the colon + increase electrolyte + water secretion => increases motility ===> diarrhoea
Which type of GI cancers usually produces visible bleeding or mucous and are often palpable on digital rectal examination
Rectal cancers
Malnutrition
insufficient dietary intake to meet current metabolic requirements
Malabsorption
disorder of digestive tract resulting in inability to use an appropriate dietary intake
Which group of people are most at risk of Vitamin B12 deficiency?
ALCOHOLICS
What is the cause of Gilbert syndrome?
harmless condition caused by excessive bilirubin due to RBC breakdown
Risk factors for acute pancreatitis
G- gallstones
E - ethanol
T - trauma
S - steroids (anabolic)
M - mumps
A - autoimmune
S - scorpion venom
H -hyperglycaemia, hypercalcemia
E - ERCP
D - drugs - valproic acid, sulphonamides, azathioprine, oestrogen preparations
major androgen secreted by the adrenal gland
Dehydroepiandrosterone
Which enzyme inactivates the active steroids -> inactive steroids?
11 beta-HSD2 dehydrogenase
Addison’s disease
Cause of : Primary adrenal insufficiency
caused by destruction or dysfunction of the adrenal cortex
Cause of Secondary adrenal insufficiency
caused by a reduction in adrenocorticotropic hormone release
Cause of tertiary adrenal insufficiency
caused by a reduction in corticotropin-releasing hormone
Acute, life-threatening presentation of Addison’s disease
Addinsonian crisis
In which type of adrenal insufficiency is an “Addinsonian crisis” most common?
Tertiary adrenal insufficiency (due to withdrawal exogenous steroids)
Reduction in glucocorticoid + mineralocorticoid hormone production
Adrenal insufficiency
What is Conn’s syndrome
Primary Hyperaldosteronism caused by XS aldosterone independent of the RAAS system
What is a Phaeochromocytoma?
catecholamine secreting tumour of chromaffin cells
Why is prothrombin time a better measure of acute liver failure compared to albumin?
because it has a shorter half-life
DEFINE
Tenesmus
feeling of incomplete evacuation
Which zone of the adrenal cortex contains lipofuscin?
ZONA RETICULARIS
Which zone of the adrenal cortex has secretory cells arranged in cords?
Zona fasiculata
Which zone in the adrenal cortex has cells arranged in irregular ovoid clusters?
ZONA GLOMERULOSA
Site of CRH release
paraventricular nucleus of hypothalamus
When are cortisol levels highest?
Morning
Most common cause of Addison’s disease (primary adrenal insufficiency)
autoimmune adrenalitis
Why can excess ACTH cause hyperpigmentation?
because it can be cleaved to alpha melanocyte stimulating hormone, bind its R and increases melanin production.
What are the effects of glucocorticoid during times of stess?
Anti-inflammatory
Immunosuppression
Approximately how many litres of food can be absorbed from the small intestine
~8.5 L due to its leaky nature
- so only small amount of material enters the lrg intestine and this is created as faeces
Proximal region of the colon (caecum) is connected to the distal ileum by the:
ileocaecal valve
What two structural mechanisms are there in the rectum to prevent unwanted release of faecal material?
Anorectal angle
Anal sphincter which is normally closed
Type 5-7 on the bristol stool chart indicates
diarrhoea + urgency
Type 3-4 on the bristol stool chart indicate
normal - easier to pass
Type 1-2 on the bristol stool chart indicate
constipation
Sulphalazine belongs to what drug class
Aminosalicylates
Which agent may used for prior surgery or investigation of the bowel?
Sodium picosulphate/ Bisacodyl => stimulant laxative which decreases water reabsorption, softening faeces
Excessive use of laxatives can cause:
Melanosis Coli -> pigmentation of lrg intestine
Tolerance
Inferior mesenteric vein drains into
splenic vein
MoA of Loperamide
acts on μ-opioid receptors in the myenteric plexus of the large intestine => anti-diarrhoeal
