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Week 9 - The Renal and Gastrointestinal Systems
w9
144
Pharmacology
Undergraduate 1
01/17/2016

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Term
What are the 4 functions of epithelial tissue
Definition
1.provide physical protection
2.control permeability and allow absorption/secretion
3.provide sensation
4.produce specialised secretions
Term
How does epithelial tissue produce specialised secretions
Definition
1.release their secretions onto the surface of the epithelium (to provide physical protection/temperature regulation)
2.release them into surrounding interstitial fluid and blood (to act as chemical messengers
Term
How is epithelia classified
Definition
by shape and its layers
Term
Describe squamous epithelia
Definition
thin and flat
Term
Describe simple squamous epithelia
Definition
Single layer
Used in absorption and secretion
Term
Describe stratified squamous epithelia
Definition
Many layers
Protects against attacks
Keratin protein adds strength and water resistance
Term
Describe cuboidal epithelia
Definition
square shaped
Term
Describe simple cuboidal epithelia
Definition
single layer
secretion and absorption
Term
Describe stratified cuboidal epithelia
Definition
Many layers
Sweat ducts and ammory ducts
Term
Describe columnar epithelia
Definition
Tall slender rectangles
Term
Describe simple columnar epithelia
Definition
Single layer
Protection, secretion and absorption
Term
Describe stratified columnar epithelia
Definition
Many layers
Protection
Term
Epithelial cells are polarised, what does this mean?
Definition
they can target proteins to discrete cell domains
Term
What is the role of a tight junction
Definition
to seal the gap between epithelial cells
prevents diffusion of plasma membrane proteins (eg receptors/channels) between apical and basolateral domains
Term
What is the role of an adherens junction
Definition
connect actin filament bundle in one cell with that in the next cell
Term
What is the role of a desmosome
Definition
connects intermediate filaments in on cell to those in the next cell
Term
What is the role of gap junctions
Definition
allows the passage of small water soluble molecules from cell to cell
Term
How can apical surfaces be specialised
Definition
Microvilli: increase membrane surface area by 20/30 fold. Especially involved in bulk absorption or secretion.
(motile) Cilia: maintain flow of fluid over the surface of epithelia
(non-motile) cilia: involved in sensing flow
Term
Define absorption and give an example
Definition
movement from the external compartment (lumen of the renal tube/gut_ to the internal compartment (blood)
eg glucose absorption in the gut and renal tube
Term
Define secretion and give an example
Definition
movement from the internal compartment to the external comparment
eg. H+ and K+ in the renal tubule; HCO3- secreted by pancreas
Term
What is net flux (Jnet)
Definition
Jabs - Jsec
mmdes/h-1
Term
How can net flux be determined
Definition
by using radioactive isotopes as tracers which we assume move in exactly the same way and by the same routes as the non radioactive solutes
Term
Describe passive transport across cell membranes
Definition
-solutes move down their electrochemical gradients
-can occur via pores/channels
-transporters facilitate diffusion of small non electrolytes (eg glucose)
Term
Describe primary active transport across cell membranes
Definition
-energy to drive comes directly from ATP
-substrate moves against an electrochemical gradient
Term
Describe secondary active transport across cell membranes
Definition
-energy to drive comes from electrochemical gradient for one substrate (set up from primary active transport)
-second substrate moves against its electrochemical gradient
Term
Describe the mechanics of NaCl transport
Definition
-apical entry of Na+
-pumped out the basal membrane into into the interstitium
-3Na+ are pumped out whilst 2K+ are pumped in (requires ATP)
-K+ is recycled via pumpa and leak
-Paracellular movement of Cl-
Term
Describe sugar absorption
Definition
-Na+ glucose symporter (driven by high extracellular Na+) enters the cell. SECONDARY ACTIVE.
-Glucose leaves the cell into the ECF via PASSIVE transport
-Na+ leaves the cell by a Na+K+ pump. PRIMARY ACTIVE.
Term
How would water move through those cells?
Definition
Moves lumen to ECF through paracellular junctions/transcellular pathway
Term
Where in the body could this represent?
Definition
Renal proximal tubule or small intestine
Term
Why does net solute movement usually drive net fluid movement?
Definition
water flows from areas of low osmotic pressure to areas of high osmotic pressure
Term
Describe the GI tract
Definition
one tube, 8-9m long, up to 15cm wide
mouth > pharynx > esophagus > stomach >small intestine >colon > rectum > anus
Term
Describe the nephrons
Definition
20-55mm long, about 50 micrometres wide

Glomerulus > proximal tubule > loop of Henle > Distal tubule > collecting duct

More than a million of them
Term
What do the kidneys maintain
Definition
the volume and composition of the body's fluids
Term
What hormones regulate the kidneys
Definition
Aldosterone
ANP
ADH
PTH
Term
What do aldosterone do?
Definition
an adrenal steroid that promotes sodium reabsorption
Term
What does ANP do?
Definition
a hormone released form the heart that promotes loss of sodium (natriuresis)
Term
What does ADH do?
Definition
a hormone released from the pituitary glands that promotes retention of water. Produces small more concentrated volume of water
Term
What does PTH do?
Definition
a parathyroid hormone that affects excretion of phosphate and calcium as well as synthesis of vitamin D
Term
Which hormones do the kidneys synthesise and release?
Definition
Renin
Vit D
EPO
Term
What does renin do?
Definition
involved in the formation of angiotensin II, a peptide with effects on the vasculature and adrenal gland.
Term
What does Vit D do?
Definition
involved in calcium and phosphate metabolism
Term
What does EPO do?
Definition
a protein that promotes formation of RBCs
Term
What is the rate of renal plasma flow
Definition
600ml/min
Term
What is the glomerular filtration rate
Definition
125ml/min
Term
How much salt is filtered each day?
Definition
1.5kg
Term
Where do the kidneys lie?
Definition
between the levels of the 12th thoracic and 3rd lumbar vertebrae
Term
Which kidney is lower than the other and why?
Definition
The right kidney is lower because it is overlain by the right lobe of the liver (and spleen)
Term
What is the source of ADH?
Definition
Adrenal glands
Term
Which is more lateral the renal cortex or renal medulla?
Definition
renal cortex
Term
How much blood plasma do the kidneys filter?
Definition
180L
Term
Describe the arterial blood supply to the nephron
Definition
Renal artery > segmental arteries > interlobal arteries > arcuate arteries > cortical radiate arteries > NOW IN THE NEPHRONS: afferent arterioles > Glomerulus > Efferent arteriole
Term
Describe the venous blood supply to the nephron
Definition
Efferent arterioles > Peritubular capillaries > OUT OF NEPHRON: venules > cortical radiate veins > arcuate veins > interlobal veins > renal vein
Term
What are the functions of peritubular capillaries and what do they surround
Definition
-provides nutrients
-retrieve reabsorbate
-remove metabolites

renal tubule
Term
State the tubular components in order
Definition
Glomerulus > Bowman's/renal capsule > Loop of Henle > distal convoluted tubule > collecting duct
Term
What is glomerular filtration
Definition
movement of plasma solutes and water across glomerular capillaries into Bowmans space and delivering a 'protein free' ultrafiltrate of plasma into the proximal tubule
Term
How is the movement of fluid caused in urine formation?
Definition
the force of filtration causes movement along the renal tubule
Term
What is tubular reabsorption?
Definition
movements of solutes and water from the lumen of the tubule back into the blood
Term
What is tubular secretion?
Definition
movements of solutes (not water) from the blood into tubular lumen
Term
What effects to diuretics have
Definition
metabolic acidosis
Term
What are APQ1?
Definition
water channels are abundant in plasma membrane of the proximal tubular cells (apical and basolateral). This allows water to move osmotically after solutes have been reabsorbed.
Term
Proximal tubule: Which compounds are actively absorbed and hence conc falls?
Definition
glucose, amino acids, bicarbonate
Term
Why does insulins conc increase
Definition
It is not absorbed or secreted by the tubule so its conc rises as water follows other absorbed solutes out of tubule
Term
Why does sodium concentration remain constant
Definition
It is the main cation in the tubular fluid. As it is reabsorbed water is being reabsorbed at the same rate, so conc remains constant.
Term
How is concentrated urine achieved in the loop of henle with no active water pumps?
Definition
-an osmotic gradient to extract the water from the tubular fluid
-the loop of henle achieves this by pumping salt into the interstitium of the renal medulla
Term
Whats present in the descending limb and what does this mean?
Definition
lots of APQ1 present
therefore high water permeability
Term
Whats present in the ascending limb and what does this mean?
Definition
lots of mitochondria
active salt pumping into interstitium making it hypertonic
Term
How is blood moved in and out of the medulla without destroying the osmotic gradient set up by the loop?
Definition
capillaries have own hairpin arrangement
blood flows down, loses water to interstitium and picks up salt
blood flows up, loses salt and picks up water
Term
What is vasopressin?
Definition
major antidiuretic hormone in mammals
Term
What does a antidiuretic do?
Definition
reduces urination
Term
What does a diuretic do?
Definition
increases urination
Term
What does the ability to produce conc urine depend on?
Definition
medullary osmotic gradient generated by loop
Term
What does change in permeability depend on?
Definition
-insertion of APQ2 water channels into apical plasma membrane
-APQ2 are only seen in principle cells
Term
What events follow when vasopressin/ADH bind to receptors in basolateral membrane?
Definition
This is a GPCR linked to adenylate cyclase, cAMP, protein kinase A which phosphorylates APQ2.
APQ2 moves to apical membrane and are inserted
Term
How does water leave?
Definition
APQ3/4 water channels on basolateral membrane
Term
What occurs when ADH levels fall?
Definition
AQP2 is retrieved endocytically and membrane returns to highly permeable state.
Term
What is the main stimulus to ADH release
Definition
plasma osmolarity
Term
What can also trigger an ADH release
Definition
fall in blood pressure/circulatory volume
Term
What is the normal osmolarity
Definition
285mosmol/kg H2o
Term
What follows increased osmolarity
Definition
Water retention or thirst
then normal osmolarity and increased ECF volume
Term
What follows decreased osmolarity
Definition
Water excretion
then normal osmolarity and decreased ECF volume
Term
What are macula densa?
Definition
specialised cells which sense the amount of water, in the glomerulus.
Term
what occurs if water levels are too high
Definition
signal afferent artery to contract, decreasing GFR
Term
what occurs if water levels are too low
Definition
stimulate the granular cells to secrete renin
Term
Functions of the GI tract
Definition
ingestion
mechanical processing
secretion (release of water, acids, enzymes, buffers and salts)
absorption (movement of organic substrates, electrolytes, vits and water)
Term
What is the Gi tracts blood supply
Definition
Coeliac artery (becomes hepatic)
Superior mesenteric artery
Inferior mesenteric artery
Term
Describe the general structure of the gi tract (inner to outer)
Definition
mucosa
submucosa
muscularis externa
serosa
Term
What are the stomach glands?
Definition
parietal cells
chief cells
g cells
Term
what do the parietal cells do
Definition
secrete hcl
Term
what do chief cells do
Definition
secrete pepsinogen (inactivates proenzyme) which is converted by hcl in gastric lumen to pepsin
Term
what do g cells do
Definition
secrete gastrin (endocrine stimulator of parietal cells)
Term
What are the functions of bile?
Definition
emulsification of fat
-dietry lipids are not water soluble
-mechanical processing in stomach creates large droplets containing lipids
-bile breaks droplets apart therefore increases surface area exposed to pancreatic lipase
Term
What are the main GI hormones
Definition
gastrin
secretin
CCK-PZ
Term
What does gastrin do?
Definition
comes from g cells and modifies acid secretion and stimulates gastrin contractions
Term
What are the 3 phases of gastric secretion
Definition
cephalic, gastric and intestinal
Term
What occurs in the cephalic phase of secretion?
Definition
1.the taste/smell/tactile sensation of food in the mouth sends nerve impulses to the medulla oblongata
2.this increases parasympathetic activity
3.vagus nerve innervate the submucosal plexus of the stomach
Term
What do the postganglionic parasympathetic fibres innervate?
Definition
parietal and cheif cells
G cells
Term
What is the outcome of the cephalic phase?
Definition
G cells increase gastrin secretion and plasma gastrin
acid and pepsinogen secretion is increased
Term
What occurs in the gastric phase of secretion?
Definition
1.begins with arrival of food in stomach
2.stimuli include:
-distension of the stomach
-increase in the pH of gastric contents
-presence of undigested food in stomach
Term
What are the short and long reflexes?
Definition
short: straight to G cells
long: chemoreceptos and mechanoreceptors
Term
What is the gastric of the cephalic phase?
Definition
Acid and pepsinogen secretion
Term
What is the stimuli for secretin?
Definition
HCl and fatty acids
Term
What is secretin secreted by?
Definition
APUD cells in duodenal mucosa
Term
What does it target?
Definition
Pancreas and liver
Term
What are the effects?
Definition
-stimulates fluid and bicarbonate secretion
-weak effects on pancreatic proenzymes and insulin
-inhibits gastric and intestinal motility
-inhibits gastric acid secretion
-example of negative feedback
Term
What is the stimuli for CCK-PZ secretion?
Definition
fatty acids, proteins and amino acids
Term
What is CCK-PZ secreted by?
Definition
APUD cells in duodenal mucosa
Term
What does CCK-PZ target?
Definition
gall bladder and pancreas
Term
What are the effects of CCK-PZ
Definition
-gall bladder contraction
-relaxation of Sphincter of Oddi
-stimulation of pancreatic secretion (bicarb and proenzymes)
-inhibits gastric emptying
-stimulates gastric and intestinal motility
Term
Describe phase 1
Definition
anticipatory phase:
affects saliva production and medulla passes on signal to stomach to produce gastrin therefore producing acid and pepsin
Term
Describe phase 2
Definition
gastric:
sensory receptors detect distension stimulates gastrin and to medulla
Term
Describe phase 3
Definition
intestinal:
as food enters the duodenum, further hormone wave is triggered which causes the release of bile and pancreatic secretions into gut lumen
Term
Which nutrients must be digested before absorbed?
Definition
carbohydrates
proteins
lipids
Term
Which nutrients can immediately be absorbed?
Definition
water
electrolytes
vitamins
Term
What do brush border enzymes digest?
Definition
tri and di saccharides
and tri and di peptides
Term
How are carbohydrates digested?
Definition
-soluble amalyse (in saliva and pancreas) breaks internal alpha1-4 bonds (not alpha1-6 bonds)
-reamining short carbs broken by brush border enzymes
-monosaccharides absorbed by 2ndary active transporters
Term
why is fructose different?
Definition
fructose monosaccharides are absorbed passively
Term
What does gastric acid do to pepsinogen in the stomach
Definition
cleaves pepsinogen hence activating it into pepsin which degrades food proteins into peptides
Term
what are proteases
Definition
enzymes that help hydrolysis of polypeptides
Term
What is the major site of protein digestion
Definition
duodenum
pepsin is inactivated here
trypsinogen is cleaved into trypsin which activates other enzymes
Term
What is the fate of the small produced peptides
Definition
diffuse into the brush border where peptidases chop them into amino acids and dipeptides
Term
Carbohydrates: how do starch/disaccharides become poly/disaccharides?
Definition
salivary amylase (mouth)
pancreatic amylase (small intestine)
1,4 alpha bonds broken only
Term
Carbohydrates: how do poly/disaccharides become mono?
Definition
broken down by specific enzymes on brush border enzymes (small intestine)
Term
Carbohydrates: what is the fate of the produced monosaccharides?
Definition
absorbed by secondary active transporters
transported to the liver via hepatic portal vein
Term
Proteins: how do proteins become large polypeptides
Definition
pepsin (from stomach glands) in presence of HCl

stomach
Term
Proteins: how do large polypeptides become small poly and small peptides?
Definition
pancreatic enzymes trypsin (small intestine)
Term
Proteins: how small poly and small peptides become amino acids?
Definition
brush border enzymes small intestine
Term
Whats their fate?
Definition
diffuse into the brush border where peptidases chop them into amino acids and dipeptides
Term
What are dietary fats?
Definition
mainly triglycerides and phospholipids
Term
Describe fat digestion
Definition
1.fats are broken down pacreatic lipase aided by bile salts which break up lipid droplets (increasing surface area)
2.mixed micelles diffuse close to the brush border, delivery contents to membrane
Term
what are mixed micelles
Definition
monoglycerides and fatty acids complex with bile salts (which solubilise them)
Term
How are mono's re-synthesised back into tri's?
Definition
once in the cell.
they must be broken down to cross the cell membrane.
Term
where is bile produced?
Definition
in the liver by hepatocytes
Term
How is bile released?
Definition
1.specific transports in the distal ileum move bile salts from the lumen of the DI to the intestinal capillaries
2.they are transported directly to the liver via the hepatic vein
Term
How are fat-soluble vitamins absorbed? examples
Definition
absorbed with lipids
dissolved in lipid droplets, micelles, chylomicrons
A, D, E and K
Term
How are water-soluble vitamins absorbed? examples
Definition
required special transport proteins (Na+)
Term
How is vit b12 absorbed? examples
Definition
absorbed only when bound to intrinsic factor
(secreted by gastric parietal cells)
Term
What would occur that meant you were no longer able to absorb vit b12?
Definition
removed part of stomach (to lose weight)
lost aprt of small intestine (Chromes disease)
Term
why is vit b12 vital?
Definition
precursor to rbc production
Term
how is gfr determined?
Definition
creatinine technique
measurement of creatinine conc and urine flow rate
Term
what occurs in the renal corpuscle
Definition
production of filtrate
Term
proximal convulated tubule
Definition
reabsorption of water, ions and all organic nutrients
Term
distal convulated tubule
Definition
secretion of ions, acids, drugs and toxins
variable reabsorption of water, sodium ions and calcium ions
Term
collecting duct
Definition
variable reabsorption of water and reabsorption or secretion na, k, h and bicarb ions
Term
papillary duct
Definition
delivery tube
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