Physl 210 B EVERYTHING FOR FINAL EXAM

GIT, Respiratory, Renal, Endocrine, Reproductive

GIT internal or external

Still considered part of the “external environment”

Main functions of GIT

Digest and absorb important nutrients, minerals and water from “external” environment to internal environment; excrete waste products and protect the host from infection/harmful substances

Upper third of GIT

Made of skeletal muscle (where we can feel swallowing in our esophagus)

Mucosa

Outermost layer of the GIT. Made of 3 sections: epithelium, lamina propria and muscularis mucosa

Villi, microvilli and crypts function

To greatly increase the surface area of the GIT

Epithelial layer

Outer part of mucosa. Main barrier for deciding what gets into the basal interior (selective uptake of nutrients, electrolytes and H2O; ensures harmful substances don’t get into the interior). Contains both villi (outward projections) and crypts (inner folds) to increase surface area. Has distinct basolateral and apical sides, helps keep specific transport proteins restricted to their sections (via tight junctions). Replaced every 5 days

Lamina propria

Second layer of the Mucosa; contains the connective tissue and all the important vessels (Blood vessels and capillaries; lymphatic drains (lacteals); nerve fibers and immune/inflammatory cells.

Muscularis mucosa

Third layer of the mucosa, contains the smooth muscle. Not responsible for GIT contraction, may be important for villi movement

Paracellular pathway

Movement of small, water soluble particles through tight junctions located in the epithelial layer

Transcellular pathway

Transport of larger molecules via transport proteins from the lumen to the basolateral surface of the cell

Submucosa

(submucosal) Plexus of nerve cell bodies; also contains connective tissue, blood and lymphatic vessels

Muscularis externa

Thick inner layer of circular muscle, involved in narrowing the lumen (responsible for contractions). Myenteric nerve plexus found here, and thinner outer layer of longitudinal muscle

Muscularis externa circular muscle function

Cause narrowing of lumen

Muscularis externa longitudinal muslce function

Shorten tube

Serosa

Connective tissue, encases intestine and forms connection to abdominal wall

GI blood circulation

Critical for carrying away water soluble absorbed nutrients from GIT to other areas of the body; also secretes hormones into GIT to aid in digestion and breakdown.

Liver blood circulation

75% from digestive organs (blood rich in nutrients and lower in O2) via portal vein; 25% from hepatic artery (oxygenated). Acts as a filter

Regulation of GIT processes

Secretion and motility most important. Governed by the amount and type of contents in GIT.

Intrinsic/enteric GIT regulation

Controls secretomotor neurons. Contained completely within GIT (brain of the gut, as many nerves as spinal cord), functions independently of CNS (involuntary). Uses two nerve networks = myenteric plexus and submucosal plexus

Myenteric plexus

In general, influences smooth muscle (contained in the muscularis externa)

Submucosal plexus

In general, influences secretion (contained in the submucosa)

Extrinsic regulation of GIT

Through autonomic NS (Para and symp); based on hunger, sight/smell of food, emotions. Recall that para allows for digestion and symp stops it.

Hormones of GIT

Released by endocrine cells into the blood. Secretin, Cholecystokinin, Gastrin and Glucose dependent Insulinotropic peptide. All peptide hormones.

Peristalsis (propulsion)

Contraction and relaxation of the two smooth muscle layers working in tandem to propel food. Longitudinal and circular always doing the opposite of one another. Muscles on top of food contract, muscles below food relax to allow for smooth passage down, towards the anus

Segmentation

Contraction and relaxation of intestinal segments where the contents are not moved forward, but rather bounced around to mix them and further break them down. Slows down transit time to allow for increased absorption and contact with digestive enzymes

GIT pacemaker cells

Located in smooth muscle, constantly undergoing spontaneous depolarization/repolarization cycles (slow waves). These propagate to the muscles via gap junctions. In the absence of stimulus, these do not produce significant contractions. Maintains the frequency of contractions

Contraction of GIT

Occurs when excitatory hormones and NT further depolarize the membrane. The more action potentials fired, the stronger the force of contraction (cannot increase the frequency of contractions, only the force).

Short GIT nerve reflex pathways

local or intrinsic pathways inside the GIT (not involved with CNS). Once hormones reach targets and bind, this is what occurs and how changes propagate.

Long GIT nerve pathways

Extrinsic pathways activated by sight, smell, food etc which relay info to CNS. These then activate the autonomic nerve pathways and got to the GIT.

Cephalic GIT control/stimulation

Receptors here are activated by seeing food, smelling food, tasting food and emotional state etc. Parasympathetic fibers then activate the GI nerve plexi.

Gastric GIT control/stimulation

Receptors here are stimulated by peptides, amino acids, distension. Hormone gastrin regulates this, as well as short/long nerve reflexes

Intestinal GIT control/stimulation

Receptors here stimulated by amino acids, peptides, distension and ___. Long and short nerve reflexes. Hormones CCK and GIP

Hypothalamus GIT functions (Food)

Lateral area responsible for hunger; ventromedial responsible for satiety. Also secretes neuropeptide Y (increase hunger) and melanocortin (decrease hunger)

Orexigenic factors

Ghrelin (Hormone secreted in stomach, causes release of Neuropeptide Y) , Neuropeptide Y (NT in hypothalamus which stimulates hunger - acts on lateral region?)

Anorexigenic factors

Leptin (from adipose tissue), Peptide YY (from intestines), Insulin (from pancreas - makes sense since glucose has to be present), Melanocortin from hypothalamus.

Leptin as an example (when satiated)

When we are intaking lots of food, more fat deposits build up in adipose tissue. These release leptin, which decreases the feeling of hunger (decreases neuropeptide Y release) and increases metabolism (to break down the food present faster).

Leptin unique case (when hungry)

When there is an absence of leptin (due to no fat deposits when food is scarce), the body increases its feeling of hunger and decreases metabolism (so you feel more hungry but can live off of less food for longer).

Regulation of water intake

Done by hypothalamus thirst centre. Main way is through osmolarity changes (even just 1%), particularly after eating a salty meal. Secondary way would be large amounts of plasma lost, if excessive bleeding, vomiting or diarrhea occurs. Dry mouth/throat also cause thirst.

When plasma osmolarity increases (related to thirst)

Osmoreceptors in the hypothalamus thirst centre cause vasopressin to be released (antidiuretic) which causes the kidneys to conserve more water.

When intense plasma loss occurs (related to thirst)

Baroreceptors in the cardiovascular system are stimulated, as well as in kidneys. Production of angiotensin 2 which increases thirst (in animals)

Obesity and Leptin

Originally thought that obese people were those lacking leptin (as shown by some mice studies where leptin is deactivated). However, for most obese people, there is actually a high concentration of leptin present, their body is just not able to recognize it properly (leptin disorder).

Salivary glands

Parotid (serous), submandibular (serous and mucous) and sublingual (mucous). Together produce ~1500mL of saliva per day. ONLY GIT COMPONENT NOT IMPACTED BY HOROMONES

Saliva composition and characteristics

Hypotonic (Low Na and Cl concentration), alkaline (rich in bicarbonate and K+), 97-99% water, digestive enzymes (lipase and amylase), some glycoproteins (mucous) and antimicrobial factors (lysozyme and lactoferrin)

Saliva functions

Begins digestion (slightly - amylase and lipase); antimicrobial properties (lactoferrin and lysozyme); lubricates mouth and food for easier swallowing and speech; buffer action against HCl if vomiting/acid reflux (bicarbonate content)

Acinar cells

Leaky (tight junctions allow ions and water through which makes the initial solution isotonic); ensure the proper proteins are present in the saliva

Myoepithelial cells

The “pump” portion of the turkey baster - push the saliva secreted by the acinar cells into the duct.

Ductal cells

Responsible for reuptake of ions (Na and Cl) which causes the saliva to be hypotonic. Very tight junctions connect these cells, not allowing for any water to leak through.

Salivary digestive components

Amylase, Lipase

Salivary production increased when

Parasympathetic is activated = smell and taste, food, nausea (about to vomit). Causes an increase of blood flow to the glands which enables the high fluid and metabolic requirements needed for increased secretion. Also increases proteins from acinar and myoepithelial cell activity.

Salivary production decreased when

Parasympathetic inactivated = sleeping, tired, fearful, some drugs

Xerostomia causes

Some drugs (inhibit parasympathetic NS), gestational (no salivary glands), autoimmune (Sjogrens), radiation treatment.

Xerostomia side effects

dry mouth, decreased oral pH (increase in tooth decay/bacteria), difficulty lubricating and swallowing food. Treatment = drink water and fluoride.

Esophagus functions and characteristics

Specialized tube which ensures food does not end up in our lungs. Top 1/3 is skeletal muscle (where we can feel ourselves swallowing), the rest is smooth muscle (where peristalsis can take place). Epithelial layer is very thick (20-30 cells), ensures that the rough food particles which the tube is exposed to do not cause damage. Also striated and smooth, which ensures that the food glides down to the stomach.

Esophageal sphincters

One at the entrance just behind the pharynx (skeletal muscle) and one at the entrance to the stomach (smooth muscle). Always closed except when swallowing, burping or vomiting. Ensures that food does not enter the airway (top) and that stomach acid is not able to “backwash” up the tube (bottom)

Heart burn

When stomach acid leaks out of the sphincter into the esophagus and is not properly neutralized. Can be caused by an inefficient sphincter, after a big meal and during pregnancy (lots of pressure on stomach).

Not a major source of absorption

What is NOT one of the functions of the stomach

Stomach fundus and body

Top portion; made of thinner smooth muscle layers. Secretes mucus, pepsinogen and HCl

Stomach antrum

Lower portion; made of thicker smooth muscle layers (for mechanical grinding and mixing). Secretes mucus, pepsinogen and gastrin

Major exocrine stomach products

Substances secreted into ducts directly onto epithelial surface: Mcuous (prevent self digestion), HCl and Pepsinogen

Minor stomach secretory products

Intrinsic factor (Vit B absorption), Gastrin (endocrine for HCl production), Histamine (paracrine release for HCl production), Somatostatin (paracrine release for HCl inhibition)

Chief cells (stomach)

Gastric gland cell found all throughout the stomach; secrete pepsinogen

Enteroendocrine cells (G cells)

Gastric gland cell found only in the antrum. Secrete the hormone gastrin into the blood (endocrine)

Enterochromaffin-like cells (ECL)

Gastric gland cell found all throughout the stomach; secretes histamine

D cells

Gastric gland cell found all throughout the stomach; Secretes somatostatin

Parietal cells

Found in gastric glands located only in the body/fundus. Produces HCl (and intrinsic factor); impacted by somatostatin, gastrin, Ach and histamine. Contains canalicular structures, which increase cell surface area - can be adjusted in size when active vs inactive.

Acidification of stomach lumen steps

Happening in Parietal Cells:

1. H+/K+ ATPase (pumps K into cell and H+ out to lumen surface - where the H in HCl comes from)

2. Carbonic Anhydrase (Catalyses the formation of H2CO3 from H2O and CO2 - H2CO3 then dissociates into HCO3 and H+; this is where the H+ is taken from to be pumped out).

3. Cl-/HCO3- exchanger (secondary active transporter which restores the pH balance of the cell; pushes out basic bicarbonate and brings in acidic Cl - Where the Cl in HCl comes from).

4. K+ channels (passive diffusion of K out of the cell to restore K balance)

5. Cl- channels (passive diffusion of Cl out to balance the loss of K ions)

Cephalic stomach phase

Starts when our brain sees, smells or tastes food. Anticipatory and excitatory; travels via the vagus nerve through the parasympathetic system

Gastric stomach phase

Major phase, begins when food reaches the stomach. Excitatory, mainly vai gastrin

Intestinal stomach phase

Mainly inhibitory, due to presence of acid and fat. Secretin, CCK and others secreted to inhibit.

Gastrin impacts (stomach)

Increases the production of HCl. Directly from blood to parietal cell and also indirectly by stimulating endochromataffin-like cells to produce more histamine.

Ach impacts (stomach)

Increases the production of HCl. Directly from the parasympathetic NS to parietal cells and also indirectly via: 1. Negatively stimulates D cells to slow production of somatostatin 2. increases production of gastrin 3. Increases production of histamine

Histamine impacts (stomach)

Increases HCl production by directly stimulating parietal cells

Somatostatin impacts (stomach)

Decreases HCl production (only one that does so in the stomach!). Stimulated by an increase in stomach acidity (more H+). Inhibited by Ach. Directly inhibits parietal cell as well as indirectly inhibits histamine and gastrin release.

Pepsinogen activation and secretion

Secreted by chief cells. Starts off in zymogen form (so as not to degrade cellular proteins) and is then activated by low stomach pH (turns into pepsin). Begins degradation of proteins; irreversibly inactivated once in the small intestine due to pH increase.

Gastric motility

Food stimulates peristaltic waves, weak contractions occur in body, strong contractions occur in the antrum. Pyloric sphincter allows a small, controlled amount of food to leave the stomach and enter the small intestine. The pyloric sphincter then slams shut and forces the food to move back into the main area of the antrum for further breakdown and mixing.

Electrical basis for gastric motility

Pacemaker cells in the smooth muscle spontaneously depolarize and repolarize in slow wave fashion (no contractions). When food is sensed, excitatory hormones and NT released causing contractions. Frequency of contractions is set in stone by pacemaker cells, strength of contraction is proportional to amount of stimulus.

Vomiting Triggers

Ejection of potential pathogens, toxins, when motion sickness occurs, when head injuries occur, when there is an infection/disturbance in the GIT and during specific sights/smells - all of which act on the vomiting centre in the medulla oblongata.

Vomitting steps

Vomiting centre in medulla oblongata is stimulated. Nausea occurs, salivation is increased (to protect against HCl), Glottis closes (to prevent vomit from going down trachea), Esophageal sphincters relax, Diaphragm and abdomen muscles contract and reverse peristalsis occurs

Vomiting benefits

Removal of harmful pathogens/toxins. Learning should occur to prevent ingestion of harmful substances in the future.

Vomiting disadvantages

Dehydration, loss of salts, loss of H+ (metabolic alkali - blood can become more basic), potential for tooth decay (enamel degradation)

Ulcers

A damaged/eroded area of the GIT mucosa, usually in the stomach and especially in the duodenum (where the lining is thinner). Caused by an imbalance between aggressive (pepsin, HCl) and protective factors (mucus and bicarbonate), H pylori, drugs which decrease prostaglandin (aspirin, ibuprofen), smoking, excessive alcohol etc.

Pancreas functions

Exocrine duct (critical for digestion, produces secretions/enzymes which go to the duodenum and digest food, as well as neutralize HCl - lots of bicarbonate production. Produces enzymes in excess, loss of absorption/digestion only noted if function falls below 10%). Also an endocrine duct (produces hormones to regulate other body functions)

Oddi Sphincter

The common sphincter which connects the pancreatic duct with the bile duct before entry into the duodenum.

Pancreatic ducts

Very similar to salivary ducts. Acinar cells produce and secrete digestive enzymes. Duct cells secrete H2O and HCO3. Pancreatic juices secreted = Isotonic solution (Na/K same concentration as blood), High in bicarbonate, high in digestive enzymes, low Cl

Highest bicarbonate concentration

Produced by pancreatic cells

Medium bicarbonate concentration

Produced by salivary cells

Base and Acid tide

How the body maintains balance of pH - parietal cells produce a lot of HCl for the stomach, which causes an “alkaline tide” of HCO3 to rush into the blood. Later, the pancreatic cells produce a lot of HCO3 for the small intestine, which causes an “acid tide” of H to rush into the blood. Blood from both of these places then flows through the portal vein and combines in the liver for neutralization.

Prevention of autodigestion

The reason why all the proteases are stored and released as zymogens from the pancreas, so they do not degrade important transport proteins and other cellular machinery found in the pancreatic cells.

Cystic fibrosis pancreatic impacts

Mutation of the CFTR Cl channel which renders it much less effective. As a result, enzymes are not washed out of the ducts by HCO3 and H2O and therefore do not reach the intestine.

Enterokinase

Stored in the microvilli in the intestine. Cleaves trypsinogen to trypsin (activates).

Trypsin

Cleaves chymotrypsinogen to chymotrypsin; Pro-elastase to elastase and Pro-carboxypeptidase A and B to Carboxypeptidase A and B. Also cleaves Prephospholipase A2 to Phospholipase A2

Trypsin, Chymotrypsin and Elastase

Pancreatic digestive enzymes which are only able to chop up proteins from the middle, therefore unable to generate individual amino acids (cannot attack N or C term)

Carboxypeptidase A and B

The only pancreatic digestive enzyme which can generate individual amino acids, by cleaving at the C term.

Amylase

Pancreatic enzyme (same as the one found in saliva). Begins breaking down alpha 1-4 bonds in amylose (linear chain portions, not able to break up the branches). Cannot generate individual glucose molecules

Lipase

Pancreatic enzyme which breaks down triglycerides into free FA and 2-monoglycerides.

Cholesterol Esterase

Pancreatic enzyme which breaks down cholesterol-esters into cholesterol and free FA

S-cells

Endocrine regulation (local, shorter pathway) of pancreatic juices. Upon stimulation by acid in the duodenum, begins release of secretin which travels via the blood to pancreatic ducts to increase HCO3 production

I-cells

Endocrine regulation (local, shorter pathway) of pancreatic juices. Upon stimulation by partially digested fat/proteins in the duodenum, begins release of CCK which travels via the blood to pancreatic acinar cells to increase enzyme production

Nerve pancreatic regulation

Longer pathway, done through the parasympathetic NS, which upon sensation of food releases Ach to the pancreatic acinar and increases enzyme production

CCK example

When FA and amino acids are present in the small intestine, CCK is triggered to be released into the blood. CCK then travels to the pancreas and increases enzyme production, and also travels to the gall bladder, causing contraction and the flow of bile into the small intestine. It then causes the sphincter of Oddi to relax, allowing the enzymes and bile (fat emulsification) into the intestine. When the fats and amino acids are sufficiently absorbed, CCK release is stopped due to negative feedback.