Out of 180 L of fluid processed through the kidneys daily, how much of it is filtered to urine?
1\.5 L
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What type of epithelium makes up the PCT
Cuboidal cells (increase SA) and large mitochondria (ATP needed for ion and solute transport)
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What does the PCT function in
Mostly reabsorption (70% volume), some secretion
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What type of epithelium makes up the loop of Henle?
Simple squamous (for water absorption) in descending limb, cuboidal to columnar cells in the thick ascending limb
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What does the loop of Henle function in?
Descending limb: Mostly water reabsorption (20% volume)
Ascending limb: Mostly Na+, K+, and Cl- reabsorption
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What epithelium makes up the DCT and collecting duct?
Cuboidal cells (smaller SA than PCT)
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What are the functions of the distal convoluted tubule and collecting duct?
Reabsorption (10% volume), hormone regulated reabsorption and secretion
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There are many mitochondria in the cuboidal cells of the DCT and collecting duct. Why?
To provide ATP for the Na+/K+ pump
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Primary vs Secondary Active transport
Primary Active transport: ATP is used to transport against concentration gradient (ex. Na+/K+ pump)
Secondary Active Transport: Mostly Na+ coupled movement (ex. Na+ and glucose)
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What is the transcellular route of reabsorption in tubules?
Across plasma membranes; apical membrane→ through cytosol→ basolateral membrane→ through interstitial fluid→ across endothelium of peritubular capillaries
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What is the paracellular route of reabsorption in tubules?
Between plasma membranes; between the ductal cells before it crosses the endothelium of the peritubular capillaries
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What is water movement driven by in tubular reabsorption?
Osmosis
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What are the three mechanisms to pulling everything back during tubular reabsorption?
1. Pulling Na+ and Na+-coupled solutes 2. Water moves towards reabsorbed solutes 3. Concentrate the remaining solutes and reabsorb through simple diffusion
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What is the most abundant cation in filtrate?
Sodium
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How does sodium transport across the apical membrane?
By active and passive transport. It uses secondary active transport as well as facilitated diffusion
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How does sodium transport across the basolateral membrane?
Primary active transport by Na+/K+ ATPase pump
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How are other nutrients and ions reabsorbed into tubular cells?
Coupled to Na+ reabsorption. This can be utilized due to the high abundance of sodium
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How is water reabsorbed into tubular cells and peritubular capillaries?
Osmosis; water moves to higher Na+ concentrations
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How does a diuretic work in regards to water reabsorption?
If an epithelial Na+ channel is blocked, sodium can’t be reabsorbed. With no sodium reabsorbed, water can’t follow via osmosis, creating a diuretic and excreting the excess water
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How are organic nutrients reabsorbed in tubular reabsorption?
Secondary active transport, co-transported with Na+; includes glucose, amino acid, vitamins, and some ions
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What is transport maximum?
Transcellular transport systems are specific and limited items must be reabsorbed while filtrate is moving. Transport maximum reflects the number of carriers in renal tubules available, amount of substance in filtrate, and glomerular filtration rate.
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How is transport maximum reached?
Tm is reached when there’s not enough carriers to pull the substance, when there’s too much substance in the system (it’s then excreted), and if the substance is being moved too fast
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True or False: Aquaporins are only sometimes present in the Proximal convoluted tubule
False; aquaporins are ALWAYS present in the PCT, this is obligatory water reabsorption
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What is facilitative water reabsorption and what hormone affects it
Aquaporins are inserted in the collecting duct only if ADH is present. Present ADH leads to more aquaporins, which leads to more water reabsorption in the collecting duct. Facilitative water reabsorption focuses on the fine tuning of hydration
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Explain passive tubular reabsorption of water
The movement of Na+ and other solutes creates an osmotic gradient for water in the PCT. Aquaporins also aid water reabsorption. Aquaporins are always present in the PCT, and only sometimes present in the collecting duct (dependent on ADH)
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Explain how passive tubular reabsorption of solutes works
When water is reabsorbed, the remaining solutes in filtrate becomes 3x more concentrated, which creates a concentration gradient. Solutes then move down their concentration gradient and utilize passive diffusion to get into peritubular capillaries. Mostly simple diffusion through the paracellular route
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What is the site of most reabsorption, including all nutrients, 70% of water and sodium, many ions, most uric acid, and 1/2 urea?
Proximal Convoluted Tubule
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T/F: Water can be reabsorbed at the descending limb of the loop of Henle but not the ascending limb
True; Water can leave and solutes cannot at descending limb, solutes can leave and water cannot at the ascending limb
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Aldosterone’s effect on reabsorption
Targets the DCT and CD; aldosterone promotes Na+ reabsorption and promotes K+ secretion; Promotes the synthesis of apical Na+ and K+ channels, and basolateral Na+/K+ ATPases (3:2); increases BP and decreases K+ blood levels
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Atrial natriuretic peptide (ANP) effect on reabsorption
Works opposite of aldosterone, inhibits Na+ reabsorption; released by specialized cardiac atrial cells if BV or BP is elevated; reduces Na+ channels on apical membrane of DCT and CD, reduces blood Na+ which reduces blood water content (water follows Na+), which decreases BV and BP
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Antidiuretic hormone (ADH) effect on reabsorption
Released by posterior pituitary, targets cells of collecting ducts; causes cells of CDs to insert aquaporins in apical membrane, promoting reabsorption of water. As ADH increases, water reabsorption increases
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Parathyroid hormone (PTH) effect on reabsorption
PTH acts on DCT and CD to increase Ca2+ reabsorption by causing greater calcium channel permeability
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Calcitonin effect on reabsorption
Calcitonin inhibits reabsorption of calcium by removing calcium channels from apical membrane; works opposite of PTH
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Where does secretion occur?
PCT, loop, DCT, CD
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Why would substances be secreted?
If there needs to be a relatively low concentration in the blood, if their bound to blood proteins that were not filtered, metabolic wastes in tubular cells
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What substances are secreted and how?
H+ (Na+-H+ exchanger); K+ (ion channel); Creatinine, penicillin, and organic acids/bases (move from peritubular capillaries through tubule cells into filtrate); HCO3- and NH4+ are synthesized in tubule cells are secreted
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Summarize H+ secretion into filtrate
Occurs in PCT and CD utilizing a Na+/H+ exchanger on the apical membrane; CO2 and H20 react to form H2CO3, which is then catalyzed by carbonic anhydrase to create H+ and HCO3-. Increased CO2 in peritubular capillary beds increases rated of H+ secretion
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How does Bicarbonate formed in the cytosol recover?
It doesn’t move across the apical membrane like H+ does, after H2CO3 is broken down into H+ and HCO3-, bicarbonate is reabsorbed into the blood.
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T/F: you pump less protons into the filtrate during exercise
False; There’s more CO2 in blood during exercise, causing proton levels to increase and be pumped out in filtrate
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What type of nephron makes up 85% of nephrons?
Cortical nephrons
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What is special about juxtamedullary nephrons?
The loop dives deep in the medulla of renal pyramids, and is surrounded by Vasa Recta (capillaries); creates more concentrated filtrate
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When does filtrate become more concentrated?
Only if the solute concentration outside of the nephron is greater that in the filtrate
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T/F: A concentration gradient allows us to concentrate urine about 4x
True
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How is an extracellular osmotic gradient created?
As NaCl enters extracellular fluid at the DCT, it increases concentration around the PCT. This drives water out of the PCT into the extracellular fluid, which causes a more concentrated solution to travel towards the DCT causing a positive feedback loop
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What happens when we inhibit the Na+-K+-2Cl- cotransporter?
We prevent salt and water uptake into the peritubular capillaries and reduce BP
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Steps of juxtamedullary nephrons creating a gradient
1. filtrate begins nearly isosmotic to blood (300 mOsm) 2. As water moves out of the filtrate down it’s concentration gradient, it causes the filtrate to concentrate 3. Filtrate reaches is highest concentration (1200 mOsm) at the bend of the loop 4. Na+ and Cl- are pumped out of the filtrate, increasing osmolarity of the interstitial fluid and decreasing concentration of the filtrate 5. Filtrate is hypo-osmotic (100 mOsm) to the interstitial fluid as it exits the nephron loop
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What is glomerular filtration rate, and why is it regulated?
GFR is the rate (volume/min) at which filtrate is collected from the blood. This is a long-term regulation of osmotic, ionic, and water balance so it therefore alters BP
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how is GFR controlled?
It’s controlled by modifying the hydrostatic pressure at the glomerular filter. Dilating the afferent arteriole increases pressure causing more filtrate to form. Increasing net filtration pressure increases filtration rate.
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T/F: decreasing glomerular hydrostatic pressure by only 18% causes the filtration rate to fall to zero
True; ex. hydrostatic pressure falling from 55mmHg to 45 mmHg
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What are the two forms of regulation of the glomerular filter? What do those branch off as?
Intrinsic controls (Renal autoregulation); Myogenic mechanism and tubuloglomerular feedback mechanism
Extrinsic controls: Sympathetic Nervous system and hormones
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Intrinsic controls of glomerular filter regulation: Myogenic mechanism
Smooth m. (granular cells) contract when stretch. Increased BP causes stretch, which leads to smooth m. contraction, which restricts blood flow into glomerulus, decreasing filtration. Dilation of afferent arterioles increases pressure, increasing filtration rate
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Intrinsic controls of glomerular filter regulation: Tubuloglomerular feedback mechanism
Macula Densa (in DCT) respond to NaCl levels. Rising NaCl levels increases filtrate flow rate, causing less time to reabsorb NaCl, which causes high filtrate NaCl levels. This causes constriction of afferent arteriole, which slows filtration pressure and rate, which allows for more time for NaCl reabsorption
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Extrinsic controls of glomerular filter regulation: Sympathetic nervous system
If extracellular fluid volume is low (low BP) it causes decreased impulses from baroreceptors, leading to sympathetic stimulation of…
1. Systemic vasoconstriction → increased BP 2. Constriction of afferent arterioles
1. decreases glomerular filtration rate, increases BV and therefore pressure 3. Increase renin release from granular cells
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Extrinsic controls of glomerular filter regulation: Hormones
Kidney’s hormonal mechanism for increasing BP; Renin is released when BP is low, there are 3 pathways to stimulate renin release by granular cells:
1. Direct stimulation of granular cells by sympathetic nervous system 2. Stimulation activated by macula densa cells in DCT when NaCl concentration is low in filtrate 3. Reduced stretched of granular cells (low pressure on afferent arterioles)
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How does the renin-angiotensin-aldosterone mechanism work to increase BP?
Renin (kidney) converts angiotensinogen (liver) to angiotensin I in the capillary endothelium. Angiotensin converting enzyme (ACE) converts angiotensin I to II. Angiotensin II stimulates aldosterone release in the adrenal cortex which stimulates the uptake of Na+ and water. Angiotensin II also stimulates vasoconstriction of Blood vessels. Both mechanisms increase blood pressure
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What are the 5 essential activities of the digestive process?
1. digestion (mechanical and chemical) 2. absorption (uptake from the outside) 3. secretions (aids in digestion) 4. motility (skeletal and smooth m.) 5. Elimination (defecation)
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What does absorption in the digestive system involve the uptake of?
Macromolecules (carbohydrates, proteins, lipids, nucleic acids), vitamins, minerals (major and trace), and water
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4 layers of the GI tract, superficial to deep
Mucosa, submucosa, muscularis externa, serosa
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Mucosa layer of GI tract
Lines the lumen of GI tract; secretes mucus, pH secretions, digestive enzymes, hormones; absorbs end products of digestion; protects against infectious disease
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Muscularis Externa layer of GI tract
Responsible for peristalsis and segmentation via inner circular and outer longitudinal muscle layers
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Sphincters of the GI tract
When the circular layer of the muscularis external thickens in certain areas; Upper esophageal, lower esophageal, pyloric, ileocecal valve, internal anal, and external anal
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Peristalsis
Adjacent segments contract and relax, propelling food along the GI tract distally
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Segmentation
Non-adjacent segments contract and relax, moving food forward then backward
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Along the GI tract, where does stratified squamous epithelia turn into simple columnar?
At the stomach
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Characteristics of simple columnar epithelia in the stomach
Composed of mucous cells that secrete a coat of alkaline (bicarbonate) mucus; Dotted with gastric pits that produce gastric juice; also contain parietal, chief, and G cells
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Parietal stomach cells
Secreted HCl and intrinsic factor
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Chief stomach cells
Secrete pepsinogen and gastric lipase
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G cells in the stomach
Secrete gastrin (hormone)
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Characteristics of simple columnar epithelia in small intestine
Has villi and microvilli to increase SA for digestion and absorption; Crypts in the villi contain mostly secretory cells that produce intestinal juice. Crypts also contain enteroendocrine cells for digestive hormones
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T/F: The entire large intestine is made up of simple columnar epithelium
False; anal canal is stratifies squamous to withstand abrasion
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Characteristics of simple columnar epithelia in large intestine
Thicker mucosa of simple columnar epithelium; no circular folds, no villi, not many cells for digestive secretions; home to numerous bacteria; abundant deep crypts with goblet cells (mucus)
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What muscle type makes up the internal anal sphincter? External anal sphincter?
Internal anal sphincter is made up of smooth muscle; external anal sphincter is made up of skeletal muscle
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What components make up the submucosa layer of the GI tract?
Made up of blood vessels, lymphatic vessels, and nerves
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What enzymes work on…
Carbs, fats/lipids, nucleic acid, and proteins?
Carbs: Glycosidases (or amylase)
Fats/lipids: lipases
Nucleic acid: nucleases
Proteins: Proteases
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What is the function of salivary amylase? Where is it secreted from? Where is it most active?
Secreted from all three salivary glands, it functions in hydrolysis of polysaccharides. (Starch or glycogen → oligosaccharide, maltose (disaccharide), and glucose (monosaccharide); most active in the mouth
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What is the function of lingual lipase? Where is it secreted? Where is it most active?
Functions in hydrolysis of lipids (Triglyceride → diglyceride + fatty acid); secreted off the surface of the tongue, most active in the stomach
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Describe mastication
Mechanical breakdown of food involving the muscles of the mouth and the teeth. The purpose is to break foodstuffs into smaller pieces and increase surface area for enzymes to have more efficient extraction of nutrients
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The glands in what areas of the stomach produce the most juice?
Parietal cells in the fundus and body of the stomach
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Function of hydrochloric acid? What secretes it?
Parietal cells secrete HCl (pH 1.5-3.5 resting); denatures proteins, can hydrolyze proteins (slowly), kills bacteria, breaks down plant cell walls (we can’t digest), and activates pepsinogen to pepsin
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Functions of intrinsic factor? Where is it secreted?
Parietal cells of the stomach exocytose intrinsic factor. It’s a glycoprotein required for absorption of vitamin B12 in the small intestine
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Function of pepsinogen? What secretes it>
Pepsinogen is the inactive enzyme that is activated by HCl or pepsin itself (positive feedback loop) into pepsin; Chief cells of the stomach secrete pepsinogen
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Function of pepsin
Chops long chain AAs into short chain AAs (works in acidic pH); proteins → peptides (smaller proteins)
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Function of gastric lipase? What secretes it?
Fat digestion; 1/3 of fat digestion occurs in the stomach; chief stomach cells secrete gastric lipase (pH 3-6); triglyceride → diglyceride + fatty acid
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Function of gastrin? What secretes it?
Gastrin is a hormone secreted by G cells in the stomach. Gastrin is secreted outside of the lumen into the bloodstream; promotes gastric mucosal growth, gastric motility, and secretion of HCl into stomach
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T/F: pepsin can digest all proteins
False; pepsin can’t digest intrinsic factor, keratin, or mucins (proteins coated in sugars)W
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Why can’t we digest sugars in the stomach?
Because then pepsin would be able to digest the walls of the stomach
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Describe the secretions into the lumen from the duodenum
Slightly alkaline, isotonic with blood plasma; 1-2 L secreted daily; largely water, enzyme poor; Duodenal (Brunner’s) glands secrete alkaline mucus to neutralize acidic chyme
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Function of bile
Emulsify lipids to speed up fat digestion
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Bile is a yellow-green alkaline solution containing…
cholesterol, neutral fats, phospholipids, and electrolytes; mostly amphiphiles; bile salts (cholesterol derivatives); bilirubin (pigmented form of heme)
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How does feces get its brown color?
Bilirubin in bile is broken down by bacteria in the intestine into stercobilin which gives the brown color
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How much does the pancreas secrete per day? What is the solution?
1200-1500 mL/day; Watery alkaline solution (pH 8) that neutralizes gastric chyme; enzymes and proteases
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What enzymes are released from the pancreas? What specific cell releases them?
Pancreatic acinar cells release pancreatic amylase (pH 6.7-7.0), pancreatic lipase (pH 7.5-8.0), pancreatic nucleases (pH>7) including ribonuclease and deoxyribonuclease, proteases including trypsinogen, procarboxypeptidase and chymotrypsinogen
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What is the function of enteropeptidase? What is activated from trypsin?
It’s a brush border enzyme in the duodenum that activates trypsin (pH 7.5-8.5) from trypsinogen. Trypsin activates proteases procarboxypeptidase and chymotrypsinogen
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List the small intestine brush border enzymes that break down saccharides
Dextrinase and glucoamylase break down oligosaccharides into monosaccharides; lactase, maltase, and sucrase break down disaccharides into monosaccharides
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What monosaccharides makes up lactose, maltose, and sucrose?
Lactose = galactose + glucose
Maltose = glucose + glucose
Sucrose = fructose + glucose
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List the small intestine brush border enzymes that break down peptides
Aminopeptides: cut off one AA from amino end
Carboxypeptides: cut off one AA from carboxyl end
Dipeptidases: cut off 2 AAs
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List the small intestine brush border enzymes that break down DNAs and RNAs
Nucleosidases and phosphatases break down nucleic acids into free bases, pentose sugars, and phosphate ions
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T/F: Digestion in the small intestine is only occurring in the lumen
False; digestion in the small intestine occurs both in the lumen and on the apical surface of microvilli
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List the functions of the liver
* Glycogen storage and glycogenolysis * Plasma protein synthesis (albumin, globulins, clotting factors) * Hormone synthesis (thrombopoietin, insulin-like growth factor, angiotensin) * Store fat soluble vitamins * detoxification of metabolites or absorbed substances * Bile production