Life Maintenance cram

Anions in pancreatic juice:

• HCO3^-

• Cl^-

• SO4^2-

• HPO4^2-

Cations in pancreatic juice:

• Na+

• K+

• Ca2+

• Mg2+ 

Secretin … the volume of pancreatic juice produced by the pancreas.
HCO3- … under it, which makes sense cos secretin promotes it and this makes the juice for alkaline. 
Cl- … because they are exchanged for biocarb ions.
Amylase … because there is a dilution effect as the volume of pancreatic juice increases. 

inc

inc

dec

dec

In the cephalic and ductile phases, explain what happens in the stimulation of acinar and duct cells

🧠 1. Cephalic and Gastric Phases (Top Left)

• Cephalic phase: Triggered by sight, smell, taste, or thought of food.

  • Sensory input → brain → Dorsal motor nucleus of the vagus.

  • Vagal stimulation (orange line) leads to parasympathetic outflow to the stomach and pancreas.

• Gastric phase: Triggered by presence of food in the stomach.

  • Particularly important in the antrum, which senses peptides and amino acids.

  • Stimulates G cells (see below).

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🧬 2. Stimulation of G Cells in the Antrum (Purple Box)

• Peptides and amino acids from digested proteins stimulate G cells.

• G cells release gastrin, which:

  • Enhances acid secretion.

  • Indirectly promotes pancreatic enzyme secretion.

• The vagus nerve also stimulates G cells via Gastrin-Releasing Peptide (GRP).

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💧 3. Acinar Cells (Bottom Right – Yellow Cells in “Acinus”)

• These cells secrete digestive enzymes (yellow blobs in the duct).

• Stimulated by:

  • ACh (vagus nerve) → binds to M₃ receptors.

  • CCK from I cells (not shown here, but released in the small intestine in response to fats and proteins) → binds to CCK_A receptors.

• Together, ACh and CCK boost enzyme secretion to digest proteins, fats, and carbs.

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💨 4. Pancreatic Duct Cells (Bottom Left – lining the duct)

• These cells secrete:

  • Bicarbonate (HCO₃⁻) and water into the ducts.

  • This neutralizes acidic chyme coming from the stomach.

• Stimulated by:

  • ACh (via M₃ receptors).

  • Secretin (not shown in this diagram, but secreted by S cells in the duodenum when pH drops).

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📉 Reciprocal Changes (from your earlier question):

• As bicarbonate secretion increases, chloride (Cl⁻) is reabsorbed (Cl⁻/HCO₃⁻ exchanger).

• So, high secretin → high HCO₃⁻, low Cl⁻ in the pancreatic juice.

Boundaries of the epiploic foramen
Ant, post, sup, inf

Ant: hepatoduodenal ligament  (inc portal triad)

Post: IVC and right crus of diaphragm (parietal peritoneum)

Sup: Liver

Inf: Superior duodenum

2 phases of drug metabolism

1. in ER. Cytochrome P450 makes substance into polar substance by adding a functional group.

2. makes product more water soluble so drug can be inactive or non-toxic for excretion

CYP inducers: CRAP GPS

Carbamazepine

Rifampin

Alcohol

Phenytoin

Grisefulvin

Phenobarbital

Sulfonylureas

Grapefruit juice inhibits which CYP

CYP 3A4

This CYP enzyme metabolises paracetemol (acetaminophen) 

CYP 1A2 

This CYP enzyme metabolises alcohol (ethanol)

CYP 2E1

This CYP enzyme metabolises warfarin (/coumadin)

CYP 2C9

This CYP enzyme metabolises cardiovascular drugs (eg Beta blockers) 

CYP 2D6

This CYP enzyme metabolises most common drugs (CCBs, statins etc)

CYP 3A4

Cirrhosis affects the following CYP enzymes 

CYP 1A2 
CYP 2E1
CYP 2C9
CYP 3A4

Hepatitis affects the following CYP enzymes 

CYP 2E1
CYP 2C19
CYP 3A

MASH (NASH) affects the following CYP enzymes 

CYP 2E1
CYP 3A

Cholestasis affects the following CYP enzymes

CYP 1A2
CYP 2E1
CYP 3A4 

What causes hepatic encephalopathy

Less ornithine cycle metabolism, NH3 accumulates and it crosses the blood-brain barrier.
Becomes glutamine and causes swelling in astrocytes which increases intracranial pressure.

can get liver flaps as a result

Why does portal hypertension happen in cirrhosis:

there is vasodilation of the splanchnic arteries meaning that more blood flows from the gut into the liver. This means there is too much blood and some is forced into the portavenous shunts (varices) in order to return to systemic flow. 

Where does the liver get most of its blood supply from

Portal vein 

Gold standard for MASLD investigation

Ultrasound guided liver biopsy

Whats hepatorenal failure

Acute renal failure in a patient with advanced liver disease, usually due to cirrhosis. 
When alive on scans, theres less blood flow but post mortem blood flow is fine and this proves its due to profound vasoconstriction due to liver failure 

Key distinction between the mucosal and systemic immune system

Mucosal prevents a pathogen getting there

Systemic deals with once the pathogen has gotten in there

Define early satiety

Feeling full without eating properly

How do affarents contribute to regulating food intake

Affarents carry messages from GIT to the brain like you should eat, stop eating, you are hungry etc

Which part of the brain controls food intake

Hypothalamus in terms of appetite, hunger, intake etc

Has the satiety centre (lateral hypothalamus) and the hunger/thirst centre (ventromedial nucleus)

What kind of lesion leads to an increase in appetite and weight gain

Ventromedial hypothalmic region

What kind of lesion leads to an decrease in appetite and thus weight loss

Lateral hypothalmic lesion

Which neurotransmitters increase appetite

Orexigenic such as NPY and AGRP

Which neurotransmitters decrease appetite

Anorexigenic such as CART and POMC

Why do diabetic patients feel hungry despite a high blood glucose

They cannot take up blood glucose to make it useful

Leptin is secreted by

White adipose tissue

Relationship between amount of adipose tissue and leptin secretion

More tissue, more leptin secreted

Effects of leptin

Decreased food intake and thus weight loss

Encourages anorexigenic factors

Effects of ghrelin

Stimulates hunger, an orexin

Stimulates food intake

Effects of obestatin

Reduces food intake

Antagonises ghrelin, even though its encoded by ghrelin gene

What produces obestatin

epithelial cells of stomach

Describe the central and peripheral effects of CCK

slows down gastric emptying and inhibits appetite if injected into the hypothalamus

Explain the consequence of hypovolemia from fluid loss via GI tract, leading to multi organ failure

• Hypovolemia happens when the body loses a lot of fluid (e.g. severe diarrhea).

• This causes less blood to return to the heart (decreased venous return).

• Less blood filling the heart means reduced preload (initial stretch of heart muscle).

• Reduced preload leads to lower cardiac output (less blood pumped out).

• Lower cardiac output causes low blood pressure (arterial hypotension).

• Low blood pressure means poor blood flow (perfusion) to tissues, including the heart.

• The heart works harder, increasing its oxygen demand.

• But oxygen supply is reduced, so heart and tissues switch to anaerobic metabolism (without oxygen).

• Anaerobic metabolism produces lactic acid, causing metabolic acidosis.

• Acidosis interferes with cell functions by damaging enzymes and reducing energy (ATP) production.

• Worsening perfusion and acidosis damage organs, leading to multiple organ failure.

• If untreated, this can cause death.

Outline the physiological response to the consequences of hypovolemia due to diarrhoea

Renal: dec GFR so less Na+ and H2O excreted

Cardiovascular: dec BP so RAAS activates and GFR as shown above

How do we get thirst as a consequence of hypovolemia

Inc plasma osmolarity sensed by osmoreceptors

Dec plasma volume sensed by baroreceptors

Angiotensin II causes thirst and triggers the release of aldosterone, which helps to conserve water and sodium.

what are gallstones made of

• bile salts (bile compounded with a cation such as sodium)

• cholesterol

• phospholipids

• bilirubin

Components of hepatic bile

• 97% water 

• cholesterol

• lecithin 

• bile acids

• bile pigments

Components of gallbladder bile

• 89% water 

• HCO3-

• Cl-

• Ca2+

• Mg2+

• cholesterole

• bilirubin

• bile salts

• lecithin

Bile secretion

CCK can stimulate the gallbladder to secrete {{c1::bile}} into the duodenum.
CCK can also send vagal afferents to the brain (dorsal vagal complex) to relax the {{c1::Sphincter of Oddi}} via NO and VIP which again allows secretion of {{c1::bile}} {{c1::Ach}} will help with contracting the gallbladder for this to happen. 

Secretin {{c1::increases}} the volume of pancreatic juice produced by the pancreas.
HCO3- {{c1::increases}} under it, which makes sense cos secretin promotes it and this makes the juice for alkaline. 
Cl- {{c1::decreases}} because they are exchanged for biocarb ions.
Amylase {{c1::decreases}} because there is a dilution effect as the volume of pancreatic juice increases. 

In which phase of gastric acid secretion are secretin and CCK significant 

Intestinal 

• Secretin: Focuses on neutralizing the acid (via bicarbonate secretion), inhibiting gastric acid secretion, and promoting bile production.

• CCK: Focuses on digesting fats and proteins by stimulating gallbladder contraction and pancreatic enzyme secretion, while also slowing gastric emptying.

Together, these hormones regulate digestion in the small intestine by ensuring proper enzyme activity, maintaining optimal pH, and controlling the rate of stomach emptying.

what do duct cells secrete

bicarbonate rich secretions such as NaHCO3 

what do acinar cells secrete

digestive enzymes

What does CCK do to the Sphincter of Oddi

Relaxes it via VIP and NO which releases bile and some HCO3- into the duodenum


CCK relaxes the sphincter of Oddi by stimulating the release of nitric oxide (NO) and vasoactive intestinal peptide (VIP), which cause the smooth muscle of the sphincter to relax. This relaxation allows the release of bile from the gallbladder and pancreatic juice (including bicarbonate) into the duodenum. Bile helps digest fats, while bicarbonate neutralizes the acidic chyme, optimizing digestion.

How do H2 antagonists help against peptic ulcers 

Blocks histamine receptors on parietal cells so less gastric acid and pepsin so this promotes healing since theres less acid
BUT STOPPING TREATMENT WILL CAUSE RELAPSE 

How do PPIs (proto pump inhibitors) help against ulcers 

Irreversibly inhibits proton pump (H+/K+ ATPase) so less H+ in lumen to form HCl 

Decreases the basal and food stimulated gastic acid secretion

How does H Pylori harm the GI tract

H Pylori is gram {{c1::negative}} and {{c1::spiral}} shaped. It has {{c1::corkscrew motility}} and flagella which allows it to penetrate the gastric mucosa. 
It is able to digest the {{c2::mucus}} layer (mucinase activity) and be detected via {{c2::Urea breath}} test because it produces ammonia from urea. this damages the mucus layer, making it more vulnerable to acid. 
It triggers {{c3::inflammation}} which weakens epithelial cells so they are more sensitive to acid. It also decreases the secretion of {{c3::bicarbonate}} ions which reduces mucosal defence. 
It increases the secretion of {{c3::gastrin}}, leading to hyperacidity. 

Whats the best method for diagnosing a peptic ulcer

Endoscopy 
EGD - eosophagagastroduodenoscopy 

Best way to treat H Pylori

Combination therapy of: PPIs with antibiotics
eg Omeprazole (PPI) with amoxicillin and metronidazole (antibiotics)

Bismuth chelate can help protect mucosa 

Symptoms of peptic ulcers

• anaemia

• nausea

• anorexia

• vomiting

• epigastric ain

• weight loss

• black, tarry stools

After paracetemol has been metabolised, what happens to the modified compounds 

Most gets excreted in urine 
Some gets converted to NAPQI (toxic) a buildup (from overdose) causes liver damage 
but glutathione neutralises it, which is also excreted in urine 

why can you not have statins and grapefruit juice

statins get degraded by a P450 enzyme called CYP3A4 which is inhibited by grapefruit juice

leads to high statin levels in blood -> liver toxicity and muscle damage

Aflatoxin B1 - liver metabolising this is harmful for body. why?

it gets activated by the P450 isoenzymes 

leads to cancer risks 

explain the phases of xenobiotic metabolism

1. oxidation: inc solubility, cytochrome P450 enzyme promotes 
2. conjugation: addition of gluthatione/ glucuronic acid/ sulfate ; inc solubility and readies for excretion 
3. elimination: transports out for excretion via urine or faeces 

NB not all compounds undergo all, this is general 
the aim is to make them harmless for excretion as urine or faeces 

what are the 3 stages of alcohol liver damage 

1. fatty liver 
2. alcohol hepatisis, group of cells die resulting in inflammation
3. cirrhosis including fibrosis, scarring and cell death 

Issues with high ethanol metabolism

It takes priority over other things

It will inhibit things like gluconeogenesis, B oxidation, Krebs etc

stimulate anaerobic respiration and ketogenesis —> lactate and ketones are acidic

How is ethanol metabolised? How can this cause issues for the body?

1. ethanol to acetaldehyde via alcohol dehydrogenase and NAD+ -> NADH and H+ (reduction) in cytosol
2. acetaldehyde to acetate via aldehyde dehydrogenase and NAD+ and H2O to NADH and 2H+ (reduction) in mitochondria 
3. acetate to acetyl CoA via acetyl CoA synthase 

Acetaldehyde inhibits enzyme function
Enhances free radical production -> tissue damage such as inflammation and necrosis

leads to less VLDL

When ethanol intake is high, alternative systems are activated:

1. Microsomal Ethanol Oxidizing System (MEOS)

• Involves cytochrome P450 2E1 (CYP2E1)

• Increases with chronic alcohol use.

• Produces reactive oxygen species (ROS) → contributes to liver damage.

• decrease in glutathione so oxidative stress

2 most important transaminases 

alanine (ALT)
aspartate (AST)

When would someone be in a positive nitrogen balance

Response to anabolic hormons
Exercise -> tissue hypertrophy
Growth (eg in kids)
Pregnancy 

Why would someone be in negative nitrogen balance 

- Muscle wasting disease
- Burns (losing tissue)
- Trauma 
- Responding to inc in catabolic hormones
- Responding to dec in anabolic hormones 

How is ammonia formed

How does pepsinogen get turned into pepsin

High H+ conc means shape gets altered by high acidity to expose active site as pepsin

Enterochromaffin-like cells (ECL) are found in fundus and body of stomach. what do they make which stimulates acid production

histamine

Where is gastric acid made

Parietal cells (in body) HCl
G cells (in pyloric antrum) Gastrin

How does CCK inhibit acid secretion

CCK has an indirect effect on acid secretion by inhibiting gastric motility and emptying. Slowing down the stomach's emptying rate allows the acid to mix with chyme more slowly, preventing over-acidification in the small intestine.

Also reduces gastrin secretion

How does Ach increase gastric acid secretion

Acts on the Mus receptors on parietal cells to increase it 

3 phases of gastric acid secretion

1. cephalic (smelling and chewing food)
2. gastric (food in stomach)
3. intestinal (food enters duodenum)

Some inhibitors of gastric acid secretion

Secretin
CCK
Somatostatin

Role of body of stomach

Secretes mucus, pepsinogen, HCl 

Role of antrum of stomach

Secretes mucus, pepsinogen, AND GASTRIN

How do parietal cells produce gastric acid 

Proton pump (H+/K+ ATPase) exchanges H+ for K+ which pumps H+ into the lumen

H+ combines with Cl- to form HCl in stomach lumen

HCO3- goes into bloodstream to maintain neutral pH

How does somatostatin help against hyperacidity

D cells secrete it 
It inhibits acid secretion by:
- acts on parietal cells to decrease HCl secretion
- inhibits gastrin release from G cells
- inhibits histamine release from ECL cells 

General note: somatostatin hates digestion it wants to stop all of it

Whereas secretin inhibits gastric acid and adds bicarbonate rich secretions to keep digestion going

How do prostaglandins inhibit gastric acid secretion

Acts on EP3 receptors on parietal cells to decrease acid secretion
Promotes production of mucus and HCO3- which protects the lining against corrosive acid 

What happens in the intestinal phase

In the intestinal phase, food enters the duodenum. There is a {{c1::high}} acidity in the duodenum which inhibits {{c1::acid secretion}}. This is so chyme does not become too acidic or pancreatic enzymes do not denature. 
Hyperacidity would disrupt bicarbonates, bile and digestive enzymes. 

How does secretin inhibit acid secretion

Inhibits parietal cells by decreasing proton pump activity for HCl production
as well as gastrin from G cells 
Also stimulates bicarbonate ions to neutralise acid

What cells secret pepsinogen

chief cells

Which oeseophageal sphincter acts as a flap valve 

Lower 

Consequences (damage) of GORD longterm

Irritates and damaged the oesophagus 
can lead to things like Barrett's oesophagus, oesophagitis, oeseophegeal ulcer, squamous cell carcinoma (cancer)

Symptoms of GORD

heartburn
coughing that keeps you awake at night 
belching 
regurgitation
dysphagia 

Whats the muscular structure of the oesophagus 

The upper 1/3 of the oseophagus has skeletal (striated) muscle 
The bottom 1/3 has smooth muscle 
There is a transition between the two where there is a mix 

Low LOS pressure from an oesophageal manometry can indicate which pathology

GORD (less than 26mmHg)
note that GORD can still happen to people with normal LOS pressure 

High LOS (more than 100mmHg) pressure indicates which pathology

Achalasia 
Because the LOS fails to relax after swallowing 

How does bismuth chelate help treat peptic ulcers

Proects mucosa by forming a base over the crater of an ulcer 

How can you test for H Pylori

Stool antigen test
Urea breath test 
Blood test
Endoscopy with biopsy

How do antacids help with GORD

Neutralises the acid - good for hyperacidity 
Increases the gastric lumen and inhibits peptic activity (because pepsin can cause oesophageal irritation) 

first line treatment for GORD

PPI such as omeprazole 

how does gaviscon (alginate) help with GORD

alginate and saliva forms a raft wich floats on the gastric lumen and protects the oesophageal mucosa from the refluxed gastric acid 

The LOS has external and intrinsic components: what are each of their general roles 

Intrinsic: oesophageal muscles which are under neurohormonal influence 
Extrinsic: Diaphragm muscles which press against the oesophagus 

These work together to prevent reflux. If they aren't working, the LOS is weakened and you get GORD 

Functions of the intrinsic components of the LOS

1. Circular smooth muscles and longitudinal muscles which maintain {{c1::basal tone}} (tension) 
2. Clasp-like semi-circular smooth muscles are found on the {{c1::right}} side. They have {{c1::myogenic}} activity meaning they can initiate their own resting contractions. They are also less responsive to {{c1::Ach}}
3. The sling-like oblique angle, aka {{c1::the Angle of His}}, is found on the {{c1::left}} side and it is responsive to {{c1::Ach}} 
They work together to prevent regurgitation 

How does the extrinsic components of the LOS prevent reflux 

The right diaphragmatic crura encircles the LOS at the oesophageal hiatus 
It has a pinch-cock action which increases pressure to prevent gastric reflux. It happens during inspiration or abdominal strain 

Which bits of the LOS components has myogenic tone

Longitudinal and circular muscles 

Explain innervation to the upper part of the oesophagus

Vagus nerve sends {{c1::somatic}} motor neurons with NO INTERRUPTIONS to {{c1::striated muscle}}
{{c1::Ach}} will cause contraction to help with swallowing 

Explain the motor innervation of the lower part of the oesophagus

Vagus nerve sends {{c1::visceral}} motor neurons WITH INTERRUPTIONS 
{{c1::Ach}} will cause contraction for peristalsis
NO and {{c1::VIP}} will cause relaxation to allow bolus to enter the {{c1::stomach}}

How do the mucosal folds in the cardia prevent reflux

They act as plugs to occlude the lumen of the gastro-oesophageal junction 
This means there is abdominal pressure pressing on the oesophagus so food would not wanna come back up as that goes against the pressure gradient