Wk 17 Flashcards
What are the normal routes of fluid intake into the body? (and their values)
What are the normal routes of fluid loss from the body? (and their values)
Oral + Metabolic = 2500mL/ day
Faeces= 200 mL
Sweat= 100mL
Urine= 1400mL
Insensible loss= 800mL
Output comes to about 2500mL as well
Where is B12 absorbed?
Large Intestine
There’s more fluid secreted into the GIT than absorbed (more absorbed in the SI but in the LI it mostly absorbs water), where does the fluid that is lost go into?
Faeces
What reflex allows some discrimination of the rectal contents and prevents unexpected voiding?
Anal sampling reflex
What are the 3 most common causes of faecal incontinence?
Structural anorectal abnormalities (sphincter trauma or fistula etc)
Neurological disorders (spinal cord injury, MS)
Altered bowel habits (diarrhoea, IBD, drugs)
What are the 3 main types of diarrhoea?
Secretory
Osmotic
Exudative/ inflammatory
What are the causes of secretory diarrhoea? 4
Bacteria like cholera (Cl- pumped into lumen)
Some laxitives (castor oil- increase intestinal secretion)
Some drugs (caffeine increases intestinal secretion)
Neuroendocrine tumours (particularly carcinoma of pancreatic islets because large amounts of VIP enhance intestinal secretion)
What are the main causes of osmotic diarrhoea? 2
Ingestion of a non-absorbable molecule
Malabsorption
What are the main causes of exudative diarrhoea? 2
Infections (ebola, e.coli, salmonella)
IBD
What is the term for when someone has blood associated with diarrhoea?
Dysentery
What is the term for the passage of fresh blood through the anus (associated with lower GIT bleeding- haemmorhoids or diverticulitis)?
Heamatochezia
What is the term for blood noticed on the toilet paper? (associated with anal fissures or haemmorhoids)
Haematopapyrus
What are the 2 centres in the brain that control the vomiting reflex?
1) Vomition centre (neural pathway)
2) Chemoreceptor trigger zone (humoral pathway)
Where is the vomition centre?
Where does it receive information from?
Medulla
Receives info from
- CTZ
- Visceral afferents from GIT (irritation, GIT distention)
- Visceral afferents from other organs (bile duct or heart)
- Afferents from other centres in the brain (odours, fear, vestibular disturbance- motion sickness)
Where is the CTZ?
Is it inside or outside BBB?
The chemoreceptors here detect multiple chemical emetic stimuli such as…
What happens after CTZ is excited?
Within the brainstem, just under floor of 4th ventricle
Outside blood brain barrier
Emetic drugs (ipecac)
Uremia
Ketoacidosis
Hypoxia
Excitatory signals are then forwarded to vomition centre
What are the 2 main electrolytes that are outside cells?
What are 4 electrolytes that are inside cells?
Outside= Na and Cl (salty outside)
Inside= K, Mg, Phosphate, Sulphate
What is an isotonic solution (in relation to a cell)
When movement of water into and out of cell is the same
What is a hypotonic solution (in relation to ECF of a cell)
What is a hypertonic solution (in relation to ECF of a cell)
When ECF is hypotonic, the conc of solutes is higher inside the cell so water moves into cell= cell swells
When ECF is hypertonic, the conc of solutes is higher outside the cell so water leaves the cell and it shrinks
What is dehydration in relation to ECF and cells?
Excessive loss of water from ECF –> Solute conc is higher in ECF than cells [hypertonic solution] –> water leaves cells to go out into ECF by osmosis –> cells shrink
What is osmolarity?
What is osmolality?
The conc of a solution (expressed as total number of solute particles per litre of solution Osm/L)
The conc of a solution (expressed as the total number of solute particles per kg of solvent Osm/kg)
What is the most abundant ion in ECF and main determinant of plasma osmolality?
What 3 functions does it regulate?
Sodium!
It regulates heart, nerve and muscle functions
What is the osmotic shift when there is hyponatraemia?
What are the 3 main causes of hyponatraemia?
Low blood sodium means there is an osmotic shift from the ECF to the ICF
Vomiting/ diarrhoea
Kidney excretion
Drinking too much water
What is the major ICF ion?
Potassium!
What is the main hormonal control of K?
A deficiency in this hormone leads to what?
Aldosterone (tells kidneys to excrete K)
Hyperkalaemia
How does acidosis affect K?
How does alkalosis affect K?
Acidosis causes a shift of K+ ions from ICF to ECF (in exchange for H+ ions)== hyperkalaemia
Alkalosis causes a shift of K+ into cell so more H+ can be released= hypokalaemia
What are the main 2 ions in gastric juice?
Na and Cl
What is transcellular movement of water and electrolyte absorption and secretion through GIT?
What is paracellar?
Transcellular is through cells and water channels (aquaporins)
Paracellular is between cells through tight junctions
Tight junctions are looser where and tighter where?
Looser in the upper SI and tighter in lower SI and colon
How does diarrhoea affect bicarb?
Massive loss of HCO3- in diarrhoea so cells GIT cells secrete HCO3- in lumen which leads to low HCO3- in blood which leads to acidosis
Blood analysis in patients with severe dehydration after diarrhoea... Bicarb? Blood acidosis or alkalosis? Hyper or hypokalaemia? Hyper or hypochloremia? Loss or normal Na+ High or low creatinine?
Bicarb depletion
Blood acidosis (due to loss of bicarb)
Hypokalaemia (due to loss of K+ in diarrhoea)
Hyperchloraemia (due to increased exchange with bicarb)
Loss of Na
High creatinine (due to low ECF vol so low renal blood flow so low GFR)
Blood analysis in someone who has had excessive vomiting…
Acidosis or alkalosis?
Hyper or hypochloraemia?
Hyper or hypokalaemia?
High or low creatinine?
Metabolic alkalosis (due to increased plasma bicarb relative to the H+ loss)
Hypochloraemia (due to loss of Cl- in vomit)
Hypokalaemia
High creatinine (due to low GFR)
What are the 2 immune cells/tissues along the GIT?
GALT- Gut associated lymphoid tissue
Peyer’s patches
Peyer’s patches are nodules of what in the wall of the small intestine?
They house _____ immune cells and facilitate immune responses against gut pathogens
They contain __ cells which lack microvilli and allow exposure to gut pathogens
Lymphoid tissue
Adaptive
M
M cells are the site of __ cell priming by ____ _____ ______ cells
M cells stimulate the development of ____-_____ __ cells
T cell priming by antigen presenting dendritic cells
Antibody-producing B cells
___ CD4 T helper cells are all throughout the ____ ____ of the SI and LI
They protect against what?
TH1
Lamina Propria
Protect against viruses
____ CD4 T helper cells are elevated in the _____ and the _____ and they protect against what?
TH17
Duodenum and jejunum
Protect against bacteria and fungus
FOXP3 T-reg cells are all throughout the SI and colon and they do what?
They dampen the immune response to limit damage
CD8 cytotoxic intraepithelial lymphocytes (IELs) are highest where in the GIT?
They sit within the ______ _____ and respond rapitly to antigen stimulation
What is the benefit of them?
Proximal SI
Mucosal epithelium
They are less reactive than CD8 T cells so there is less uncontrolled inflammation and also they are good at killing viral infected cells
BUT
They can induce barrier breach during inflammation which is bad
Where are IgA producing plasma cells in the GIT and what do they do?
They are present throughout the SI and elevated in the colon
They produce IgA which is secreted into the mucus of the lumen
The IgA binds to target microbes within the gut lumen for immune recognition
What cells samle food and microbial antigens?
What do they activate if there is no threat?
What do they activate if they sense a threat?
Dendritic cells
T-reg cells to dampen immune response
Antigen specific T-helper cells such as TH1 and TH17
Rotavirus….
Infects epithelial cells of the GIT which are lost into the lumen, this causes what?
What is essential to counteract dehydration?
Causes a reduced absorptive ability of the immature cells to absorb sugar, salts and water so you get diarrhoea and dehydration
Fluid and salts
What is the incubation period of Noravirus?
How many hours does it last?
Virus invades and destroys _____ and ____ villus epithelium and this leads to decreased absorption of what from the bowel lumen?
12-48 hours
12-60 hours (half a day to 2 and a half days)
middle and upper
Decreased absorption of Na and water
Clostridium botulinium…
Where are toxins produced?
Toxins are absorbed in the blood and block neurotransmission of _______ _____
What are the symptoms? 3
Food or in the gut
Peripheral nerves
Paralysis, muscle weakness and resp arrest
What is the bacteria that gives people food poisoning if they eat undercooked pork?
What is the food poisoning that occurs when rice cools to room temp and is reheated?
Clostridium perfringens
Clostridium cereus
Which bacteria can be spread by flies?
What are the symptoms?
Shigella
39 fever and crampy abdo pain first, then diarrhoea and dysentery
What is the treatment for Helminths (Parasitic worms)?
Albendazole
Autonomic NS control of GIT motility and secretions…
Parasymp stimulation releases ___ onto __ receptors in the GIT –> increases ____ plexus activity –> increases GIT motility and secretions
Too much GIT mobility= ____
Ach onto M3 receptors
Increases enteric plexus
Too much= diarrhoea
GIT motility and secretions cont…
Sympathetic stimulation releases ___ or ___ onto __, __, or __ ______ receptors in the GIT which inhibits _____ plexus activity= ___________
Too little GIT motility=
NA or Adrenalin onto a1, a2 or B2 adrenergic receptors
inhibits enteric plexus= relaxation of smooth muscle and decreases GIT motility
Constipation
3 approaches for severe acute diarrhoea?
1- anti-infective agents (antibiotics)
2- fluid and electrolyte replacement
3- use of spasmolytic (reduces smooth muscle spasm) or other antidiarrhoeal agents (opiods)
Enteric neurons express high levels of opiod receptors (some are also on secretory cells of GIT)…
What does stimulation of u-opioid receptors do?
What does stimulation of delta opioid receptors do?
u= decrease GIT motility delta= decrease secretions
What is the main opiod receptor agonist that we give for anti-diarrhoea?
It stimulates ____ receptor –> inhibits ___ release –> ___ longitudinal and circular smooth muscle of GIT –> _____ GIT motility
(May also do what?)
Loperamide (Imodium)
u-opioid receptor
inhibits Ach release
Relaxes muscle
Decreases motility
May also reduce GIT secretions
What type of diarrhoea are bile acid sequestrants used for?
What is the one we use called?
How does it work?
Chronic diarrhoea
Cholestyramine
Binds to bile salts
Where is the CTZ?
In the area postrema, which is on the floor of the 4th ventricle and outside the BBB
What is the receptor for…
Serotonin?
Dopamine?
Acetylcholine?
Cannabinoids?
Substance P?
Serotonin= 5HT receptor
Dopamine= Dopamine D2 receptor
Ach= Muscarinic M1 receptor
Histamine= Histamine H1 receptor
Cannabinoids= CB1 receptor
Substance P= neurokinin NK1 receptor
Ondansetron is a ______ ___ receptor antagonist
Serotonin is released by _______ cells in the SI in response to chemo
‘____s’ inhibit 5HT receptors on ____ afferents in periphery and prevent the signal to CNS
Inhibit 5HT receptors in CTZ and Solitary Tract Nucleus centrally which prevents activation of _____ centre
serotonin 5HT
Enterochromaffin cells
‘Setrons’ vagal
emetic
Metaclopramide and domperidone are _______ receptor antagonists
Inhibit ______ __ _____ in CTZ and STN
How do they stimulate GIT motility?
Where else do they have (weak) antagonist action?
Dopamine
Dopamine D2 receptors
Stimulate GIT motility because blocking Dopamine receptors causes the stimulation of Ach on M3 receptors on GIT smooth muscle
Weak antagonist action at 5HT receptors
What is the main Neurokinin NK1 (substance P) receptor antagonist?
How does it work?
What is it used for?
Aprepitant
Block the effects of sustance P in the CTZ and STN (Solitary tract nucleus)
Chemo induced sickness and post-op sickness
What are the 2 main histamine H1 receptor antagonists?
Most effective for what?
Blocks effects of ____ in _____ afferents and ____ __ receptors in ___
Promethazine and cyclizine
Mositon sickness and vestibular disturbances
Histamine
Vestibular
Histamine H1 receptors
STN (Solitary tract nucleus)
What is the most common Muscarinic M receptor antagonist?
Most effective for what?
Block the effects of ___ in _____ afferents
Hyoscine hydrobromide (Kwels)
Motion sickness and vestibular disturbances
Ach in vestibular afferents
