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Transcript
Cell Bio Phys Review 2
Lecture 10
SodiumPotassium
Pump
• Basolateral side
• Generates negative
sodium balance inside the
cell
• Allows for sodium to be
pumped into cell from
lumen
• 3 Na for 2 K
Nutrientcoupled
Na+ Transport
• JEJUNUM AND ILEUM
POST-PRANDIAL
STATE
• activating Na+/glucose
and Na+/amino acid cotransporters to get sodium
into the cells
• Again, sodium pumped
into interstitium by Na-KATPase
Na-H
Exchanger
• Duodenum + Jejunum
• Alkalinity is high – postprandial state due to
HCO3
• pH gradient pulls H out of
epithelial cell, pushes Na
in
• HCO3 gets put into blood
Interdigestive
period
• Distal Ileum and Colon
• Na-H transporter
• HCO3- and Cltransporter
• CHLORIDE GETS
ABSORBED
• Both H and HCO3 come
from H20 and CO2
POTASSIUM
ABSORPTION
• Jejunum and Ileum, K+
absorption occurs
passively, likely from
solvent drag
• Active K+ absorption –
DISTAL COLON
• Use of K+-H+ pump
Electrolyte
Transport in
Colon
• ALDOSTERON
STIMULATED
• Na absorbed, K secreted
• THIS IS HOW K IS SECRETED
• Last line for Na absoprtion
• Similar to late distal tubule and
collecting ducts of the kidney
• FLOW-RATE DEPENDENT
• DIARRHEA
• HYPOKALEMIA / tx
hyperkalemia
• Hyperchloremic metabolic acidosis
with normal anion gap
CHLORIDE
SECRETION –
drives secretion
• Basolateral surface
• ACh and VIP stimulate
• Activate Adenyl Cyclase and
cAMP
• Open the Cl- channel in
apical membrane
• Na+ and H20
• Cholera toxin
• A subunit
• ADP ribosylation of Alpha-s
subunit
• Inhibits GTPase activity
• Always on
Summary Slide
Diarrhea
Osmotic
• Cause – presence of nonabsorbable solutes in the
lumen
• Lactase deficiency
• Lactose accumulates in lumen
and retains water
• Bacteria break it down and
make it smaller molecules,
increasing osmosis
Secretion
• Excessive secretion of fluid
by crypt cells
• Bacteria – cholera/E. Coli
A 14 year old ballerina reports that she has chronic diarrhea. A detailed
history reveals that she frequently drinks skim milk, that she does not use
laxatives, and that she has noticed that her condition improves during times
that she fasts for religious observances. In contrast to secretory diarrhea,
which of the following is most likely seen with osmotic diarrhea?
• A) It is characterized by an increase in the stool osmotic gap
• B) Result of increased cell secretion
• C) Result of decreased electroneural sodium absorption
• D) Caused by bacterial toxins
• E) Occurs only in the colon
Lecture 11
Basic Liver anatomy
• Blood Supply – 2 sources
•
•
•
•
Hepatic artery proper – 25% and oxygenated
Hepatic portal vein -75% and nutrient rich
IVC drains it
10% of body’s total blood
• Anatomical unit– liver lobule
• Hexagonal cylindrical structure
• At center – central vein
• Functional unit – hepatocytes
• Separated by sinusoidal capillaries – bathe hepatocytes
• Fluid flow
• High flow
• High compliance
• Low – resistance
• Leaky endothelial cells – large fenestrations and large
gaps between adjacent cells
• Space of Disse - Gap between basolateral membranes
of hepatocytes and sinusoidal wall
Space of Disse
Gap between basolateral
membranes of hepatocytes and
sinusoidal wall
• Ito cells
• Store fat/fat soluble
• Inflammation 
myofibroblasts
• FIBROSIS
(Ito cell)
Basolateral
membrane
Apical
membrane
KUPPFER CELLS
• MAIN ROLE = REMOVE UNWANTED
PARTICLES
• EARLY EHTANOL-INDUCED LIVER INJURY
• TNF-ALPHA AND ROS
• TURNS ON THE STELLATE CELL
MINOR ROLE – BREAK DOWN RBCS
BILIRUBIN
• REMOVE FROM BLOOD
• CONJUGATE IT
• UDP glucuronosultransferase (UGT1A1)
• BABIES!!!!
• Excreted into bile
• Intestines
• Deconjugate – urobilinogen
• Reabsorb or oxidize to urobilin - urine
• Urobilinogen – converted to stercobilin and gets feces
Fasting
Post-Prandial State
•
Glycogenolysis + gluconeogenesis
(amino acids and fats)
• Glycogen storage
•
Regulation
• Convert fat to storage
•
•
•
Glucagon - stimulates
B2 receptors - stimulates
Insulin – inhibits
Lipids
•
Acetyl-coa is converted to ketone bodies
by b-oxidation
•
Ketone bodies (acetoacetate and bhydroxybutyrate) can be use by the body
for energy
•
FYI: the liver can’t use ketone bodies
for energy
• Insulin stimulates
glycogenesis
Proteins
• Liver doesn’t’ store AAs
• Synthesize
• Nonessential Aas
• ALT and AST
• Albumin and clotting factors
• Catabolism
• Generates 10% of body NH3
• Converts most of NH3 to urea
• Neurotoxic.
Lipids 101
Exogenous
• Chylomicrons – small
intestine
• Lipoprotein lipase in blood
– digests Triglycerides to
muscle and adipose tissue
• Liver takes up rest of
chylomicrons and throws it
in bile
Endogenous
• Synthesize lipoproteins
• VLDLs – changed to IDL
and LDLs in blood
• Short half life
• Returned to liver
• High LDLS – good.
• Produced cholesterol esters
Acute Liver failure
• ACETAMINOPHEN*****
• NEW ONSET < 26 WEEKS DURATION
• COAGULOPATHY
• JAUNDICE
• ENCEPHALOPATHY
• NO FIBROSIS!!!!!
CHRONIC LIVER FAILURE
• ALCOHOL ABUSE****/VIRAL HEPATITIS
• FIBROSIS
• IRREVERSIBLE = CIRRHOSIS
• PORTAL HTN
• ASCITES – ALBUMIN AND FLUID LEAK INTO AB
CAVITY
• ENCEPHALOPATHY – WHY? NH3
• COAGULOPATHY
LFTs
• ALT and ALT – hepatocyte death
• ALP – bile flow obstruction
• GGT –damage to cholangiocytes
Unconjugated
•
•
Pre-hepatic
• Increased production
Hepatic
• Decrease liver uptake
• Decrease liver conjugation
• Varying deficits in
UGT1A1 activity
• Neonatal jaundice
• GilbertMeulengracht
syndrome
• Crigler-Najjar
syndrome
Conjugated
• Decrease liver secretion
• Dubin-Johnson
syndrome
• Decrease liver outflow
• Cholestasis
• Post-hepatic
• Extrahepatic bile duct
blockage
• Gallstones