GI Flashcards
Protective roles of liver
Immunity
- Kupffer cells
- Synthesis of complement
- Synthesis of Ig
Detoxification
- Phase I metabolism
- Phase II metabolism
- First pass metabolism
Regulatory roles of liver
- Reservoir for blood
- Glucostat
- Catabolism
- Coagulation
- Storage
- Oncotic pressure
- Hormonal
Regulation of hepatic flow
1.5L/min or ~25% of CO (100ml/min/100g)
HBF = (mHAP - HVP)/ hepatic arteriolar resistance
Local
Hormonal
Autonomic
Intrinsic
- Autoregulation
- Hepatic arterial buffer response (semi-reciprocal relationship between hepatic artery and portal vein)
- Hepatic venous pressure
Extrinsic
- Neural/ autonomic
- Humoral (glucagon, AT-II, vasopressin)
- Digestion/ exercise
- Respiration
- Blood gases
- Haemorrhage
- Anaesthesia
Clinical laboratory assessment of liver function
- ALT (7-55 U/L)
- AST (8-48 U/L)
- ALP (40-129 U/L)
- GGT (8-61 U/L)
- Bili (total) (3-20 umol/L)
- Albumin (40g/L)
- INR (0.9-1.1)
Vomiting
Involuntary, forceful and rapid expulsion of gastric contents though the mouth.
Mechanism - consists of a set of processes coordinated by the vomit centre in the medulla oblongata, and is divided into 3 phases
Pre-ejection phase
- Prodromal nausea
- Salivation
- Retrograde intestinal contractions which forces intestinal contents into stomach
Retching phase
- Deep inspiration and breath-holding to splint the chest
- Epiglottic closure
- Elevation of the soft palate (prevents nasal soiling)
- ↑IAP
Expulsive phase
- Relaxation oesophageal sphincters
- Pyloric contraction
- Violence contraction of the diaphragm and abdominal muscles
- Forces gastric contents out through mouth
Control of vomiting
Vomiting centre
- Integrates sequence of vomiting
- Scattered groups of neutrons in NTS/ lateral reticular formation of medulla/ lower pons
=> Associated with respiratory, vasomotor, and salivary centres
Chemoreceptor trigger zone
- Located bilaterally in the floor of the 4th ventricle in the area postrema near the vagal nuclei
- External to BBB and sensitive to chemical stimuli/ circulating substances
=> Rich with D2 and 5-HT3 receptor which signal to voimt centre
Vestibular apparatus
- Impulses from endolymph movement in the utricle and saccule of the vestibular apparatus are relayed via the vestibular nucleus and eight nerve to the CTZ
- H1 and M1 are activated by vestibular stimuli such as motion sickness and signal to vomit centre
Enteric irritants
- GIT irritants send impulses to medulla via vagus nerve/ sympathetic afferents to trigger vomiting
- 5-HT release from enterochromaffin cells in small intestine triggers vagal afferents that stimulate CTZ and trigger vomit centre
=> Via intestinal 5-HT3 receptors that transmit signal via NTS to vomiting centre
Afferent pathways
- Stretch and chemoreceptors throughout the GIT via the vagal and sympathetic nerves
- Pharyngeal touch receptors via the glossopharyngeal nerve and the cerebral cortex
- Cerebral cortex - higher senses and emotions
Efferent pathways
- Vagus (X), hypoglossal (XII), glossopharyngeal, (IX), trigeminal (V), facial (VII) nerves to the upper gut and the spinal nerves to the diaphragm and abdominal muscles
- Five principle NT receptors mediate N+V
=> M1, D2, H1, 5-HT3, NK1 (neurokinin 1) - substance P
Opioids
- Sensitise the vestibular apparatus to movement induced emesis
=> Act via MOP in CTZ - may also act directly at NTS
- Delay gastric emptying
Liver function
Metabolism - CHO, proteins lipids, ketones, alcohol. Glucostat
Excretion - bile + urea. Regulations and storage in and release from gallbladder by CCK. Transports lipid soluble substances into GIT for excretion.
Detoxification - toxins + drugs. First pass metabolism, Phase I + II reactions
Synthesis - plasma proteins, bile, coagulation related factors, bilirubin. Maintains oncotic pressure + blood volume
Storage - glycogen, vitamins, metals
Hormonal - synthesis, activation, degradation. EPO, angiotensinogen, activates Vit D
Haem - blood reservoir, procoag + anticoagulant + fibrinolytic
Immunological - innate and adaptive, Kupffer cells, complement, acute phase proteins
Hepatic blood flow measurement
Using the Fick Principle + indicator indocyanine green.
Dye removed from circulation only in the liver and is almost entirely excreted in bile. Does not have an enterohepatic circulation. Level measured in blood by spectrophotometry using absorption peak of 805nm.
Constant infusion until steady state. Rate of infusion must equal hepatic uptake (as only site of removal).
Hepatic arterial concentration is the same as the level in any peripheral artery. The hepatic vein level is determined by sampling from a catheter in the hepatic vein.
Gastric emptying hormones
Increase
- Ghrelin
- Motilin
- Gastrin
Decrease
- CCK
- Secretin
- Gastric inhibitory polypeptide (GIP)
- Glucagon
- GLP1 + 2
Factors effecting gastric emptying
Local - food, duodenal distension
Neural - enteric, autonomic
Hormonal
Physical - pH, fat >protein, duodenal distension, osmolarity, antral distension
Pharmacological
Higher centres - pain, fear, excitement
- Position (fastest upright or R) lat)
- Consistency (liquid > solid)
- Volume of liquid (larger empties faster)
- Gastric pH (acidic pH decr rate of emptying)
- Tonicity (decr emptying)
- Lipid (slows emptying)
- Caloric content (high calorie slows emptying)
- Labour (delayed up to 48hrs post partum)
Others reducing
- Gastroparesis
- DM (neuropathy)
- EtOH, opioids, recreational drugs
- Trauma within last 2hrs
- Acute abdo
Mediators
- 5-HT3 main mediator and incr emptying
- CCK and 5-HT1 delay
Inhibit gastric emptying
- Duodenal distension
- Vagotomy - i.e autonomic neuropathy
- Drugs - opioids, alcohol, anticholinergics
- Extremes of pH and osmolality of gastric contents
Gastric emptying food
Liquid <30mins
CHO 2-3hrs
Protein 3-4hrs
Fat 5-6hrs
Barrier Pressure
= LOS pressure - intra gastric pressure
Normally = 20mmHg
LOS = 30, IGP 10
If <13 -> GORD
LOS (Lower oesophageal sphincter) tone
Hormonal factors
- Increased LOS tone – gastrin, CCK, motilin, a-adrenergic stimulation, estrogen
- Decreased LOS tone – progesterone (pregnancy), PGE2, glucagon, VIP, GIP, secretin
Physical factors
- Increased intra-gastric pressure usually accompanied by a rise in LOS tone
- Cough/sneeze 🡪 increase intra-gastric pressure 🡪 increase tone
- Swallowing 🡪 transiently decrease LOS tone to allow passage of food into stomach (via NO)
Physiological state
- Obesity 🡪 low LOS tone
- Pregnancy 🡪 low LOS tone
- Hiatus hernia 🡪 low LOS tone
-> LOS intrathoracic and increased IAP results in reduction in barrier pressure
Goblet cells (neck cells)
- Secrete mucous
- Layer of HCO3 which protect from pepsin and acid
- PGs incr production
Chief cells
- Secrete pepsinogens and gastric lipase (pepsinogen converted to pepsin in low pH)
