Small Intestine Flashcards

1
Q

Q. What is the function of the small intestine?

A

A. To absorb nutrients, salt & water

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2
Q

The duodenum, jejunum & ileum

Introduction

The small intestine is about metres long in adults and has several key roles, of which the most important is the absorption of water and nutrients to sustain life. The small intestine originates immediately after the stomach, and coils around the abdomen (held in place by the …………….) until it meets the large intestine in the …………… ………….. quadrant. It is functionally separated from these structures by two sphincters; the …………… sphincter at the proximal end, and the …………….. valve at the distal end.

The small intestine is conventionally separated into three portions as listed below (with approximate lengths in parentheses), however where one portion starts and another finishes is less clear as they all have the same basic histological structure.

The duodenum: (0.25 m) - key roles in ……………. and …… ………………..

The jejunum (2.5 m) - key roles for …………………

The ileum (3.75 m) - key roles for ………………..

The small intestine has the same general structure as the rest of the gut tube, with three noteworthy features:

The epithelial layer has finger-like projections called ………….which enormously increase the internal surface area. These villi are motile and have a rich blood supply and lymph drainage

The mucosa is arranged in ………. (like a concertina)

It has invaginations called crypts of …………….

A

The duodenum, jejunum & ileum

Introduction

The small intestine is about six metres long in adults and has several key roles, of which the most important is the absorption of water and nutrients to sustain life. The small intestine originates immediately after the stomach, and coils around the abdomen (held in place by the mesentery) until it meets the large intestine in the lower right quadrant. It is functionally separated from these structures by two sphincters; the pyloric sphincter at the proximal end, and the ileocaecal valve at the distal end.

The small intestine is conventionally separated into three portions as listed below (with approximate lengths in parentheses), however where one portion starts and another finishes is less clear as they all have the same basic histological structure.

The duodenum: (0.25 m) - key roles in digestion and gut regulation

The jejunum (2.5 m) - key roles for absorption

The ileum (3.75 m) - key roles for absorption

The small intestine has the same general structure as the rest of the gut tube, with three noteworthy features:

The epithelial layer has finger-like projections called villi which enormously increase the internal surface area. These villi are motile and have a rich blood supply and lymph drainage

The mucosa is arranged in folds (like a concertina)

It has invaginations called crypts of Lieberkühn

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3
Q

What is the mesentery’s function?

A

Fan shaped mesentery;

  • throws the small intestine into folds
  • supports the blood supply.
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4
Q

The Digestive Epithelium

What type of muscle does the external wall have?

How is the internal mucosa arranged?

What is the mucosa covered in?

What are the invaginations known as?

A
  • External wall has longitudinal & circular muscles (important for motility).
  • Internal mucosa arranged in circular folds.
  • Mucosa covered in villi (~1mm tall).
  • Invaginations known as Crypts of Lieberkühn.

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5
Q

What type of cells make up the mucosa?

Wha type of cells make up the crypts of lieberkuhn?

A

Cell types of the small intestine

Mucosa lined with

–simple columnar epithelium consisting of

  • primarily enterocytes (absorptive cells)
  • scattered goblet cells
  • enteroendocrine cells

•In Crypts of Lieberkühn, epithelium includes

  • Paneth cells
  • stem cells
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6
Q

What is the most abundant cell type in the small intestine?

What is its shape and where is its nuclies located and does it have microvilli?

What is it specialised for?

A

Enterocytes

  • Most abundant cells in small intestine.
  • Tall columnar cells with microvilli & a basal nucleus.
  • Specialised for absorption & transport of substances.
  • Short lifespan of 1-6 days.
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7
Q

Microvilli

  • Microvilli (~0.5-1.5mm high) make up the “……….. ……………”.
  • There are several thousand microvilli per cell
  • The surface of the microvilli are covered with …………………….
  • Glycocalyx

–rich carbohydrate layer on apical membrane that serves as protection from the digestional lumen, yet it allows for absorption.

–traps a layer of water & mucous known as the “……………layer” which regulates rate of …………… intestinal lumen

A

Microvilli

  • Microvilli (~0.5-1.5mm high) make up the “brush border”.
  • There are several thousand microvilli per cell
  • The surface of the microvilli are covered with glycocalyx
  • Glycocalyx

–rich carbohydrate layer on apical membrane that serves as protection from the digestional lumen, yet it allows for absorption.

–traps a layer of water & mucous known as the “unstirred layer” which regulates rate of absorption from intestinal lumen

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8
Q

What is the 2nd most abundant cell type in the small intestine epithelium?

What is the apical part of the cytosol packed with which distorts the shape of the cell?

What does mucous consist of and what do in the small intestine besides protection?

What is the relationship between these types of cells and the length of the intestine? State why

A

Goblet cells

These cells are the second most abundant cells in the small intestinal epithelium.

The apical part of the cytosol is packed with mucin granules, which distorts the shape of the cell (like a goblet).

Mucous consists of water and glycoproteins, and serves as a lubricant to facilitate gut passage.

This is especially useful as water is constantly being absorbed from the lumen, which steadily dehydrates the contents.

Because of this, the number of goblet cells increases along the entire length of the intestine.

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9
Q

What shape is enteroendocrine cells?

Where are they often found in the intestine?

What is its function?

Where is its sensory appuratus located?

Where are the collections of manufactured hormones stored?

A

Enteroendocrine Cell

  • Columnar epithelial cells, scattered among the absorptive cells
  • In the intestine, most often found in the lower part of the crypts.
  • Hormone secreting - eg to influence gut motility (see Regulation of function lecture).
  • In older text books might find them referred to as chromaffin cells (affinity for chromium/silver salts).

These are hormone secreting epithelial cells, most commonly found in the bottom of the crypts. They are roughly columnar in shape. Their sensory apparatus is in the apical portion, and collections of manufactured hormones are kept near the basolateral membrane ready to secrete into the local blood supply.

Selected examples include:

G-cells secrete gastrin

I-cells secrete cholecystokinin

S-cells secrete secretin

D-cells secrete somatostatin

Some enteroendocrine cells can also be closed, which means they are not exposed to the gut lumen at all.

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10
Q

What are the immunological cells of the small intestine known as?

Where are they located?

These cells contrain a high number of acidophillic grancules. List 3 thing that they contain and state why they have them?

A

Paneth cells

These are immunological cells. They are located at the bottom of the crypts and contain a high number of acidophilic granules. Granules contain:

lysozyme: an antibacterial enzyme
glycoproteins: to protect local cells from enzymes
zinc: a common cofactor for lysozymes

Paneth cells are located near the stem cells, so their priority is probably to help protect these progenitor cells, as opposed to protecting the other cells of gut. On top of their lysozyme granules, they also engulf bacteria and regulate the intestinal flora.

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11
Q

Stem cells

Enterocytes and goblet cells have a very short lifespan of about 36 hours. These cells are continually being replaced by stem cells from the bottom of the crypts.

Pluripotent stem cells proliferate in the crypts and ‘move up’ the sides of the villus towards the tip. Shortly after they reach the top they become senescent and naturally slough off, get broken down and reabsorbed. This is a continuous ‘escalator’ of birth, migration and death of epithelia.

This process is extremely energy intensive and is essential to the normal operation of the gut. It allows:

The effects of gut-borne toxins/drugs to eventually run their course - it is ‘easier’ to continually replace these cells than protect the huge numbers of cells at risk

Lesions will be short-lived and repaired quickly

Following radiation therapy/exposure, stem cell activity is impaired and this usually results in severe GI dysfunction

A
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12
Q

What are the distinguishing features of the duodenum?

A

Duodenum

Distinguished by presence of Brunner’s Gland

Coiled mucous-secreting submucosal gland which secrete a bicarbonate-rich alkaline solution which open up into the base of the Crypts. Helps to neutralise acid chyme and protect the lining of the proximal small intestine and provide an optimum pH for enzymes.

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13
Q

What are the distinguishing features of the jejunum?

A

jejunum

Large submucosal folds called plicae circularis. These are similar to the folds in the rest of the small intestine, but they are considerably larger and closer together. They look much more like frills than folds.

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14
Q

What is the distinguishing feature of the illeum?

A

Ileum

The ileum has up to 100 Peyer’s patches, which are aggregates of specialised lymphoid tissue that are key to the immune response to gut-borne pathogens

. They are able to initiate leukocyte and immunoglobulin responses to pathogens.

These patches contain M-cells (key for immunity, see later lesson) which do not have microvilli like the neighbouring enterocytes.

  • Shares some features with the large intestine
  • The ileum has a lot of Peyer’s patches- large clusters of lymph nodules in the submucosa.
  • Prime immune system against intestinal bacteria (other mechanisms for defence = bactericidal Paneth cells, rapid cell turnover).
  • Well positioned to prevent bacteria from colon migrating up into small intestine
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15
Q

Summary: Cell types

A

Enterocytes

–Absorptive (covered by microvilli), most abundant, frequent renewal

Goblet cells

–mucous secreting

Enteroendocrine cells

–hormone secreting

Paneth cells

–antibacterial, protect stem cells

Stem cells

–migrate up villus ‘escalator’, pluripotent

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16
Q

Motility

Intestinal motility has three main functions:

Name them

These functions are achieved via three mechanisms:

Name them

A

Motility

Intestinal motility has three main functions:

To mix ingested food with digestive secretions and enzymes

To facilitate the contact between contents and mucosal surface

To propel the contents along the small intestine

These functions are achieved via three mechanisms: segmentation, peristalsis and the migrating motor complex.

17
Q

Summary of motitilty

A

•Segmentation

–mixing

•Peristalsis

–propelling

•Migratory Motor Complex

–sweeps through gut, preventing accumulation of residue

18
Q

Digestion of macronutrients

The secretions that facilitate digestion in the small intestine are principally derived from the liver (and gall bladder), the pancreas and the small intestine wall. These enzymes work optimally in an alkaline environment, which requires the integration of other mechanisms to ensure this happens.

Enzymes tend to be effective at two sites:

Enzymes that cleave big nutrients into smaller nutrients operate in the gut lumen (usually released from glandular organs)

Enzymes that cleave dimeric nutrients into monomers for absorption are in the brush border of the enterocytes (usually released from the gut epithelium)

A
19
Q

Digestion in The Duodenum

In the small intestine digestion occurs in an alkaline environment.

Digestive enzymes & bile enter the duodenum from the pancreatic duct and bile duct.

  • The duodenal epithelium also produces its own digestive enzymes.
  • Digestion occurs both in the lumen and in contact with the membrane.
A
20
Q

Where does the dirst stage of carbohydrate digestion occur and what enzyme is responsible?

When does digestion of carbohydrates resume and what enzymes breakdown these carbohydrates.

A

Digestion and absorption of carbohydrates

Overview

The first stage of carbohydrate digestion occurs in the mouth via salivary amylase (but this is a minor effect). There is no digestion of sugars in the stomach, and digestion resumes in the duodenum via pancreatic amylase and brush border enzymes.

Complex carbohydrates: long polymers in basic chains or branched chains

Simple carbohydrates: disaccharides and monosaccharides

The goal of digestion is to break the long polymers into simple monomers that can be absorbed by the gut wall.

21
Q

Which part of the pancreas is alpha-amylase secreted?

What does this enzyme need and what structure in the duodenum help it do this?

A

Pancreatic a-amylase

  • Secreted into duodenum in response to a meal
  • Continues digestion of starch & glycogen in the small intestine (started by salivary amylase)
  • Needs Cl- for optimum activity & neutral/slightly alkaline pH (Brunner’s glands in duodenum = alkaline secretion)
22
Q

Describe the absorption of Carbohydrates and mention the channels as well for the carbohydrate monomers?

A

Absorption

Glucose and galactose are absorbed through the apical surface by secondary active transport through the SGLT-1 transporter (Sodium Glucose Linked Transporter 1) and fructose undergoes facilitated diffusion through GLUT-5 (GLUcose Transporter 5) channels. All three monosaccharides diffuse down their concentration gradient through the basolateral membrane using GLUT-2 channels.

The SGLT-1 transporters are supporters transporting one carbohydrate and one glucose into the cell at a time. Sodium is pumped out of the basolateral surface by a sodium potassium ATPase to ensure the sodium gradient.

23
Q

Where does protein digestion begin?

  • Pancreatic proteases are secreted as ………………..
  • ……………… is activated by enterokinase, an enzyme located on the duodenal brush border.
  • ……………… then activates the other proteases.

Brush border peptidases break down the larger peptides prior to absorption.

Amino acids are absorbed by ………………… ………………. and …………… ………………. …………………. (similar to sugars).

Di- and tri-peptides are absorbed using …………….. …………….. distinct from single amino acids.

Cytoplasmic peptidases break down most of the di- and tri-peptides before they cross the basolateral membrane.

A

Digestion of Proteins

  • Protein digestion begins in the stomach by pepsin, but pepsin is inactivated in the alkaline duodenum.
  • Pancreatic proteases are secreted as precursors.
  • Trypsin is activated by enterokinase, an enzyme located on the duodenal brush border.
  • Trypsin then activates the other proteases.

Brush border peptidases break down the larger peptides prior to absorption.

Amino acids are absorbed by facilitated diffusion and secondary active transport (similar to sugars).

Di- and tri-peptides are absorbed using carrier proteins distinct from single amino acids.

Cytoplasmic peptidases break down most of the di- and tri-peptides before they cross the basolateral membrane.

24
Q

Lipid Digestion​

The first stage of digestion is in the mouth where ……………. ………….. hydrolyses triglycerides. After swallowing, digestion continues in the stomach by ingested ………………… ……………… and secreted ………………. ………………, which cleaves single fatty acid chains from free triglycerides. The mechanical churning of the stomach slightly ………………. the fats to increase their surface area.

A

Lipid Digestion​

The first stage of digestion is in the mouth where lingual lipase hydrolyses triglycerides. After swallowing, digestion continues in the stomach by ingested lingual lipase and secreted gastric lipase, which cleaves single fatty acid chains from free triglycerides. The mechanical churning of the stomach slightly emulsifies the fats to increase their surface area.

  • Lipids are poorly soluble in water, which makes them more complicated to digest.
  • Four stage process in the small intestine

–Secretion of bile and lipases,

–Emulsification

–Enzymatic hydrolysis of ester linkages,

–Solubilization of lipolytic products in bile salt micelles.

25
Q

Digestion of lipids

A

Digestion

As acid chyme leaves the stomach, fats are still largely intact (undigested), and as bile enters the duodenum it provides chemical emulsification with huge increases in surface area by creating small fat droplets. Pancreatic juice is secreted simultaneously, which acts on this large surface area to cleave two fatty acid chains from the triglycerides to form monoglycerides and free fatty acids (via pancreatic lipase & colipase). This is luminal digestion, and as the digestion products reach the brush border they are combined with bile salts to form micelles, which are soluble enough to cross the aqueous unstirred layer

26
Q

What is the function of bile salts?

A

Emulsification

Water and fat don’t mix.

  • Bile and lipases are secreted into the duodenum.
  • Bile salts facilitate the emulsification of fat into a suspension of lipid droplets (~1mm diam).
  • The function of emulsification is to increase the surface area for digestion.
  • Allows pancreatic lipase to split triglycerides
  • A triglyceride is broken down into two fatty acids and a monoglyceride at fat/water interface.

27
Q
A
28
Q

What does colipase do?

A
29
Q

Other important lipid enzymes

A

Phospholipase A2 hydrolyses fatty acids at the 2 position in many phospholipids, resulting in lyso-phospholipids and free fatty acids.

Pancreatic cholesterol esterase hydrolyses cholesterol ester to free cholesterol and fatty acid.

30
Q

Absorption of lipids

Once in the brush border, lipolytic products diffuse through the apical membrane and bile salts remain in the lumen (they travel through the small intestine and get reabsorbed in the terminal ileum).

Once in the cell, monoglycerides and free fatty acids are resynthesized into triglycerides via two separate pathways.

The primary mechanism is the ……………… …………… pathway, and the secondary mechanism is the…………………. ………………. (the details of these catabolic pathways are not essential information). Once resynthesized, triglycerides are packaged with proteins, phospholipids and cholesterols into a lipoprotein called …………………., which are exocytosed and, as they are too large to enter the capillaries, they enter the lymphatic system (via the villi’s lacteal).

A

Absorption of lipids

Once in the brush border, lipolytic products diffuse through the apical membrane and bile salts remain in the lumen (they travel through the small intestine and get reabsorbed in the terminal ileum).

Once in the cell, monoglycerides and free fatty acids are resynthesized into triglycerides via two separate pathways.

The primary mechanism is the monoglyceride acylation pathway, and the secondary mechanism is the phosphatidic pathway (the details of these catabolic pathways are not essential information). Once resynthesized, triglycerides are packaged with proteins, phospholipids and cholesterols into a lipoprotein called chylomicrons, which are exocytosed and, as they are too large to enter the capillaries, they enter the lymphatic system (via the villi’s lacteal).

31
Q
A
32
Q
  • The ileum is separated from the colon by the ……………….. ……………
  • Relaxation and contraction controls the passage of material into the colon.
  • Also prevents the back flow of bacteria into the ileum.
A
  • The ileum is separated from the colon by the ileocaecal sphincter.
  • Relaxation and contraction controls the passage of material into the colon.
  • Also prevents the back flow of bacteria into the ileum.
33
Q

Summary digestion

A

•Carbohydrate digestion

–Pancreatic a amylase & brush border enzymes

•Protein digestion

–Trypsin, which activates other proteases

•Lipid digestion

–Emulsification by bile, hydrolysis & solubilisation into bile salt micelles

34
Q

do questions at end of slide

A

do questions at end of slide