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Blood vessels Lymph vessels Nerves Smooth muscle Connective tissue lymphocytes Plasma cells Eosinophiles Villous epithelium Undifferentiated Goblet Mitoses Endocrine cells Crypt epithelium Crypt lumen Muscularis mucosa Absorp- tive cells Goblet cells Endocrine cells Cell Loss

Blood vessels Lymph vessels Nerves Smooth muscle Connective tissue lymphocytes Plasma cells Eosinophiles Villous epithelium Undifferentiated Goblet Mitoses

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Page 1: Blood vessels Lymph vessels Nerves Smooth muscle Connective tissue lymphocytes Plasma cells Eosinophiles Villous epithelium Undifferentiated Goblet Mitoses

Blood vesselsLymph vesselsNervesSmooth muscleConnective tissuelymphocytesPlasma cellsEosinophiles

Villousepithelium

Undifferentiated

GobletMitoses

Endocrine cells

Cryptepithelium

Cryptlumen

Muscularismucosa

Absorp-tive cells

Gobletcells

Endocrine cells

Cell Loss

Page 2: Blood vessels Lymph vessels Nerves Smooth muscle Connective tissue lymphocytes Plasma cells Eosinophiles Villous epithelium Undifferentiated Goblet Mitoses

• Crypts of Lieberkuhn: Small and Large Intestine

- Contain Primarily Epithelial Cells, Mucus Goblet Cells, and Endocrine Cells.

- Water Secretion - VIP Activates Water Secretion by Elevating cAMP and Cl- conductance.

- Cell Growth and Differentiation: Cell Turnover at the Tip of a Villus is High (3-6 day Cycle).

Secretions of the Small Intestine (2000 ml/day)

Page 3: Blood vessels Lymph vessels Nerves Smooth muscle Connective tissue lymphocytes Plasma cells Eosinophiles Villous epithelium Undifferentiated Goblet Mitoses

Crypt Secretion

H2O2 Cl-

Na+ K+

PDtecAMP? Ca2+

Cl-

Cl-Na+

ATPADP + Pi

3 Na+

2 K+

Key Players:

cAMP Activated Cl- Channel

Na+ / K+ / Cl- Co-transport

Na-K ATPase

VIP – neurotransmitter Histamine also can activate

Page 4: Blood vessels Lymph vessels Nerves Smooth muscle Connective tissue lymphocytes Plasma cells Eosinophiles Villous epithelium Undifferentiated Goblet Mitoses

Daily Secretions into the Alimentary Canal

• Saliva 1200 7.0-7.4• Gastric secretion 2000 1.0-

3.5• Pancreatic secretion 1200 8.0-8.3• Bile 700

7.8• Intestinal Secretions 2000 7.4-7.8• Brunner’s gland secretion 50 (?) 8.0-8.9• Large intestinal secretion 60 7.5-

7.8

• Total 7210

Daily Volume (ml) pH

Page 5: Blood vessels Lymph vessels Nerves Smooth muscle Connective tissue lymphocytes Plasma cells Eosinophiles Villous epithelium Undifferentiated Goblet Mitoses

Blood vesselsLymph vesselsNervesSmooth muscleConnective tissuelymphocytesPlasma cellsEosinophiles

Villousepithelium

Undifferentiated

GobletMitoses

Endocrine cells

Cryptepithelium

Cryptlumen

Muscularismucosa

Absorp-tive cells

Gobletcells

Endocrine cells

Cell Loss

Page 6: Blood vessels Lymph vessels Nerves Smooth muscle Connective tissue lymphocytes Plasma cells Eosinophiles Villous epithelium Undifferentiated Goblet Mitoses

Sugar Absorption

-Amylase

Lactose Sucrose

Starch Glycogen

30% 70%

Glucose

Galactose Na+Fructose

Glucose

Na+

-Limit Dextrins Oligosaccharides

LactaseGlucose Carrier

Fructose Carrier (Xylose)

Glucose Carrier Gluco-

amylase

Sucrase -Dex trinase

LUMEN

Brush Border

Page 7: Blood vessels Lymph vessels Nerves Smooth muscle Connective tissue lymphocytes Plasma cells Eosinophiles Villous epithelium Undifferentiated Goblet Mitoses

• Absorption of Nutrients: Carbohydrates- Glucose and Galactose - Sodium Co-

transporter Across Luminal Membranes- Fructose - Facilitated Transport

(Na+ Independent)- Xylose: Pentose; Uses the Fructose

Carrier not Na+ Dependent.

ABSORPTION

Page 8: Blood vessels Lymph vessels Nerves Smooth muscle Connective tissue lymphocytes Plasma cells Eosinophiles Villous epithelium Undifferentiated Goblet Mitoses

Capillary

Amino Acids

AminoAcids

SmallPeptides

Carrier Peptidases Carrier Mediated

IntracellularPeptidases

?

Free Amino AcidsNeutral Basic Acidic

Large Peptides

Small Peptides

Pepsin, Pancreatic Protease

Protein

A.A

Page 9: Blood vessels Lymph vessels Nerves Smooth muscle Connective tissue lymphocytes Plasma cells Eosinophiles Villous epithelium Undifferentiated Goblet Mitoses

Emulsion: TG. MG. FFA. B.S.

Micelles MG. FFA. B.S.

Large oil droplet(TG)

MG. FFA

Intestinal epithelial cell

Microvilli

LipaseCo-Lipase

Lipid Digestion and Absorption

Page 10: Blood vessels Lymph vessels Nerves Smooth muscle Connective tissue lymphocytes Plasma cells Eosinophiles Villous epithelium Undifferentiated Goblet Mitoses

Triglyceride Monoglyceride

Pancreaticlipase

Free fattyacids

Glycerol

Lacteal Capillary

MicelleLiver

IleumConjugated bile salts

Monoglycerideacylation pathway

Phosphatidicacid pathway

Protein (Apo B)

Cholesterol

Chylomicron

Phospholipids

FABP

Page 11: Blood vessels Lymph vessels Nerves Smooth muscle Connective tissue lymphocytes Plasma cells Eosinophiles Villous epithelium Undifferentiated Goblet Mitoses

Nutrient Digestion and Absorption

-Only Monomers and small digestion products can be absorbed.

For amino acids and carbohydrates, most absorption is Na+dependent

- Lipids are digested before absorption, then re-synthesized in epithelia cells before packaging and secretion into lymph

Glycerol and Monoglycerides diffuse into the blood.

Complex fats are packaging into chylomicrons and secreted to the lymph.

Lymphatic flow increased 10X during absorption of a high fat meal.

Page 12: Blood vessels Lymph vessels Nerves Smooth muscle Connective tissue lymphocytes Plasma cells Eosinophiles Villous epithelium Undifferentiated Goblet Mitoses

Blood vesselsLymph vesselsNervesSmooth muscleConnective tissuelymphocytesPlasma cellsEosinophiles

Villousepithelium

Undifferentiated

GobletMitoses

Endocrine cells

Cryptepithelium

Cryptlumen

Muscularismucosa

Absorp-tive cells

Gobletcells

Endocrine cells

Cell Loss

Page 13: Blood vessels Lymph vessels Nerves Smooth muscle Connective tissue lymphocytes Plasma cells Eosinophiles Villous epithelium Undifferentiated Goblet Mitoses

Relations Between Salt /Water Secretion and Absorption

Net Fluid and NaCl Villus Epithelia Absorption

Net Fluid and NaCl Crypt EpitheliaSecretion

Page 14: Blood vessels Lymph vessels Nerves Smooth muscle Connective tissue lymphocytes Plasma cells Eosinophiles Villous epithelium Undifferentiated Goblet Mitoses

Crypt Secretion

H2O2 Cl-

Na+ K+

PDtecAMP Cl-

Cl-Na+

ATPADP + Pi

3 Na+

2 K+

Key Player:

cAMP Activated Cl- Channel

CFTR

VIP – neurotransmitter Histamine also can activate formation of cAMP

Page 15: Blood vessels Lymph vessels Nerves Smooth muscle Connective tissue lymphocytes Plasma cells Eosinophiles Villous epithelium Undifferentiated Goblet Mitoses

Absorption of Na+

Concentration in Chyme: Na+ Conc. K+ Conc. Volume

Duodenum

Ileum

Colon (Prox)

140 mEq/L

125 mEq/L

40 mEq/L

5 mEq/L

23 mEq/L

80 mEq/L

5 Liters

1 Liter

200 mL

Page 16: Blood vessels Lymph vessels Nerves Smooth muscle Connective tissue lymphocytes Plasma cells Eosinophiles Villous epithelium Undifferentiated Goblet Mitoses

• Na+ is Absorbed Along the Entire Intestine

- Na+ Diffuses Down its Electrochemical Gradient into Epithelial Cells

- Luminal Membrane: Co-transport with Nutrients, Diffusion Through Na+ Channels and Na+/H+ Exchange

- Transported Across the Basolateral Membrane by the Na-K ATPase.

- Cl- Moves to the Blood to Maintain Electroneutrality.

Absorption of Na+

Page 17: Blood vessels Lymph vessels Nerves Smooth muscle Connective tissue lymphocytes Plasma cells Eosinophiles Villous epithelium Undifferentiated Goblet Mitoses

25-OH-D3

1,25-(OH)2-D3

Liver

Kidney

Intestine

RNA

Ca2+Ca2+

Na+

PlasmaCa2+

Ca2+ ATPase

CaBP

CaBP

Parathyroid Hormone

Vitamin D3

Page 18: Blood vessels Lymph vessels Nerves Smooth muscle Connective tissue lymphocytes Plasma cells Eosinophiles Villous epithelium Undifferentiated Goblet Mitoses

Vitamins

Fat Soluble – absorbed all along the intestinevia normal fat absorptive pathways.

(D, K, A)

Water Soluble: Specific Transport

Most all along the intestine.

Several Ileal Specific- Vitamin: B12

also Ileal Specific: Bile Salts.

Vitamins and Ileal Transport

Page 19: Blood vessels Lymph vessels Nerves Smooth muscle Connective tissue lymphocytes Plasma cells Eosinophiles Villous epithelium Undifferentiated Goblet Mitoses

- 90-95% of Water (re)absorption in the Small Intestine

- 1-2 L/day is Absorbed in the Colon.

- A Normal Colon Can Reabsorb a Maximum of About 4.5 liters per day.

• Mechanism of H2O Absorption-

– Where salt goes, so too does water.

Absorption of Water

Page 20: Blood vessels Lymph vessels Nerves Smooth muscle Connective tissue lymphocytes Plasma cells Eosinophiles Villous epithelium Undifferentiated Goblet Mitoses

• The Causes of Diarrhea Delineate into 3 Categories

• Motility Based: Limiting Time for Absorption

Bacterial Infiltration

• Malabsorption; Maldigestion: Osmotic

- Lactase Deficiency

- Ileal Resection: Biles Salts also stimulate secretion.

- Celiac Disease (Sprue; Gluten Sensitive) – Xylose Test

• Secretory: Initiated by Effectors which Alter cAMPLevels in Enterocytes; Bile Salts

Pathophysiology of Diarrhea