Gastric Secretion and Acid Production

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Questions and Answers

What is the main function of hydrochloric acid (HCl) in gastric juice?

Neutralize alkaline substances

Digest carbohydrates

Destroy pathogens and aid in protein digestion (correct)

Increase absorption of nutrients

The stomach produces up to 3 liters of gastric juice every week.

False

What is the role of intrinsic factor in gastric secretion?

Intrinsic factor is essential for the absorption of vitamin B12.

The ______ cell is primarily responsible for the secretion of hydrochloric acid in the stomach.

parietal Signup and view all the answers

Match the components of gastric juice with their functions:

Hydrochloric acid = Creates an acidic environment for digestion Pepsinogen = Enzyme that digests proteins Gastric lipase = Enzyme that digests fats Mucus = Protects the stomach lining from acid Signup and view all the answers

What is the pH range of gastric juice?

1-3 Signup and view all the answers

The stomach's main function is to filter the blood.

False Signup and view all the answers

What is chyme?

Ingested food plus stomach secretions Signup and view all the answers

The stomach stores food and produces _____ for digestion.

gastric juice Signup and view all the answers

Match the gastric gland cells with their functions:

Parietal cells = Secrete hydrochloric acid (HCl) Chief cells = Secrete digestive enzymes Mucous cells = Produce mucus Enteroendocrine cells = Release hormones Signup and view all the answers

Which function is NOT associated with gastric motility?

Absorbing nutrients directly Signup and view all the answers

Gastric slow waves are involved in the relaxation of the stomach's orad region.

True Signup and view all the answers

What is the effect of swallowing food on the smooth muscle cells in the stomach?

They relax. Signup and view all the answers

The process by which the stomach fragments and mixes food is called ______.

mixing Signup and view all the answers

Match the following gastric motility functions with their descriptions:

Receptive Relaxation = Allows the stomach to increase volume without a significant rise in pressure Mixing = Fragmenting food and combining it with gastric secretions Emptying = Regulating the passage of gastric contents into the duodenum Vagus nerve = Coordinates with the enteric nerve plexuses for stomach function Signup and view all the answers

What are the two primary types of inflammation?

Acute and Chronic Signup and view all the answers

Acute inflammation is characterized by a prolonged duration compared to chronic inflammation.

False Signup and view all the answers

List two macroscopic features of acute inflammation.

Erythema and Oedema Signup and view all the answers

Inflammation is a response to an ______ that aims to eliminate the cause of injury.

injury Signup and view all the answers

Match the following inflammation types with their descriptions:

Acute Inflammation = Immediate defensive reaction of tissue to injury Chronic Inflammation = Prolonged and persistent inflammation Sepsis = Excessive response of inflammation Autoimmune Disorders = Inappropriately triggered inflammation Signup and view all the answers

What is the term for oxygen deprivation that impairs aerobic metabolism?

Hypoxia Signup and view all the answers

Ischemia is better than hypoxia because it allows for the delivery of nutrients.

False Signup and view all the answers

What is the key event in the development of many diseases related to cellular responses?

Cell death Signup and view all the answers

Severe and progressive injury leads to _____ and may result in either apoptosis or necrosis.

cell death Signup and view all the answers

Match the following causes of cell injury with their descriptions:

Oxygen deprivation = HYPOXIA that impairs aerobic metabolism Nutritional imbalances = Lack of essential nutrients for cell survival Physical agents = Mechanical trauma and temperature extremes Infectious agents = Pathogens causing cellular damage Signup and view all the answers

Which of the following represents a potential cellular adaptation to non-lethal cell damage?

Hypertrophy Signup and view all the answers

Cellular adaptations are irreversible changes that occur in response to environmental changes.

False Signup and view all the answers

What term describes the change in cell type in response to stress or injury?

Metaplasia Signup and view all the answers

Hyperplasia is characterized by an increase in ______ of cells in a tissue.

number Signup and view all the answers

Match the types of cellular adaptation with their definitions:

Hyperplasia = Increase in cell number Hypertrophy = Increase in cell size Atrophy = Decrease in cell size or number Dysplasia = Abnormal cellular growth and organization Signup and view all the answers

Which part of the small intestine is primarily responsible for digestion?

Duodenum Signup and view all the answers

The jejunum is the longest segment of the small intestine.

False Signup and view all the answers

What are the three segments of the small intestine?

Duodenum, jejunum, ileum Signup and view all the answers

The small intestine has an absorptive surface area of about _____ m².

4500 Signup and view all the answers

Match the following functions with their corresponding segments of the small intestine:

Duodenum = Main site for digestion Jejunum = Main site for absorption Ileum = Absorption of nutrients and bile salts Plicae circulares = Increase surface area for absorption Signup and view all the answers

Which type of prevalence measures the proportion of individuals with a condition at any point in their lives?

Lifetime prevalence Signup and view all the answers

Period prevalence refers to the proportion of individuals with a condition at a specific point in time.

False Signup and view all the answers

The measure known as ______ prevalence captures the proportion of individuals with a condition at a specified point in time.

point Signup and view all the answers

Match the following terms with their definitions:

Point Prevalence = Proportion at a specific time Period Prevalence = Proportion during a time interval Lifetime Prevalence = Proportion at any point in life Prevalence = General measure of how common a disease is Signup and view all the answers

What is the primary purpose of the Hospital Episode Statistics?

To cover all hospital activity Signup and view all the answers

What chapter does diabetes mellitus fall under in the ICD-10 classification?

Chapter IV: Endocrine, nutritional and metabolic diseases Signup and view all the answers

What does TFR stand for in the context of birth statistics?

Total Fertility Rate Signup and view all the answers

The underlying cause of death is defined as the disease or injury that initiated the train of morbid events leading directly to death.

True Signup and view all the answers

What is the primary purpose of the Medical Certificate of Cause of Death?

To certify the fact of death and provide information on the cause of death. Signup and view all the answers

The _______ is a local registrar responsible for births, marriages, and deaths.

Registrar Signup and view all the answers

Match the following terms with their definitions:

ICD10 = International Classification of Diseases Coroner = Official who investigates deaths TFR = Total Fertility Rate Mortality Statistics = Statistics related to deaths in a population Signup and view all the answers

What is required for a valid informed consent?

Assessment of capacity Signup and view all the answers

Informed consent is necessary only for major medical procedures.

False Signup and view all the answers

What philosophical concept is central to the idea of informed consent?

Autonomy Signup and view all the answers

To avoid a charge of battery, a doctor must have a valid _____ from the patient.

consent Signup and view all the answers

Match the following forms of consent with their appropriate situations:

Informed Consent = Treatment procedures Implied Consent = Emergency situations Written Consent = Research participation Verbal Consent = Routine examinations Signup and view all the answers

Which of the following is NOT a key example of an antacid?

Sodium bicarbonate Signup and view all the answers

Alginates are primarily used to increase the acidity of stomach contents.

False Signup and view all the answers

What is the primary mechanism by which antacids counteract stomach acidity?

Buffering gastric acid Signup and view all the answers

Alginates form a viscous gel upon binding water, which helps to protect the _______ from acid reflux.

oesophageal mucosa Signup and view all the answers

Match the following drugs to their classifications:

Aluminum hydroxide = Antacid Calcium carbonate = Antacid Alginates = Viscous gel agent Magnesium hydroxide = Antacid Signup and view all the answers

Study Notes

Gastric Secretion

The stomach produces up to 3 litres of gastric juice per day.
Gastric juice contains hydrochloric acid (HCl), enzymes like pepsinogens and gastric lipase, intrinsic factor and mucus.
Gastric juice is secreted from gastric glands in the gastric mucosa.

Acid Secretion

The concentration of H+ in the gastric lumen can reach 150mM.
This results in gastric luminal pH of between 1-2.
The parietal cell plays an important role in the secretion of gastric acid.
It contains a proton pump (H+/K+ ATPase) on its apical membrane.
The parietal cell also contains a chloride channel on its apical membrane and a Na+/K+ ATPase on its basolateral membrane.
A bicarbonate/chloride exchanger helps regulate chloride transport between the parietal cell and blood.

Hydrochloric Acid Production

CO2 from blood enters the parietal cell.
In the parietal cell, CO2 combines with H2O to form H2CO3 (carbonic acid) in the presence of carbonic anhydrase (CA).
H2CO3 dissociates into HCO3- and H+.
H+ is pumped out into the stomach lumen using the H+/K+ ATPase (proton pump), in exchange for a K+.
HCO3- leaves the cell via the HCO3-/Cl- exchanger into the blood in exchange for Cl-.
Cl- ions move to the lumen by facilitated diffusion.
H+ and Cl- combine in the gastric lumen to form HCl.

Regulation of Gastric Secretion

Gastric acid secretion is regulated by both neural and hormonal mechanisms.
Three phases contribute to gastric secretion:
- Cephalic phase: This phase begins before food enters the stomach.
- Gastric phase: This phase starts once food enters the stomach.
- Intestinal phase: This phase begins as partially digested food enters the duodenum.

Cephalic Phase of Gastric Secretion

The taste or smell of food, or even thoughts about food, can stimulate the medulla oblongata.
This leads to parasympathetic action potentials via the vagus nerves to the stomach.
The vagus nerve stimulation results in HCl and pepsin secretion from parietal and chief cells.
Gastrin is also secreted in this phase.
Gastrin circulates back to the stomach and further stimulates HCl and pepsin secretion.

Gastric Phase of Gastric Secretion

Distention of the stomach triggers a parasympathetic reflex.
Action potentials are carried by the vagus nerves to the medulla oblongata.
The medulla oblongata then stimulates further secretions to the stomach.
Distention also stimulates local reflexes that further amplify stomach secretions.

Intestinal Phase of Gastric Secretion

Partially digested food (chyme) enters the duodenum, and if the pH of the chyme is less than 2 or if it contains lipids, it inhibits gastric secretions.
This occurs through three mechanisms:
- Sensory input from the duodenum to the medulla inhibits motor input from the medulla to the stomach.
- Local reflexes inhibit gastric secretion.
- Secretin, gastric inhibitory polypeptide, and cholecystokinin produced by the duodenum inhibit gastric secretions in the stomach.

Physiological Regulation of Gastric Acid Secretion

Stimulation of Gastric Secretion:
- Gastrin
- Acetylcholine
- Histamine
Inhibition of Gastric Secretion:
- Somatostatin
- Prostaglandins E2 and I2
- Intestinal hormones

Stimulation of Gastric Acid Secretion

Cholinergic nerves: Release acetylcholine (ACh).
Muscarinic receptor: ACh binds to this receptor on parietal cells.
ECL cells: Secrete histamine.
Gastrin receptor: Gastrin binds to this receptor on ECL cells.
H2-receptor: Histamine binds to this receptor on parietal cells.
Gastrin receptor: Gastrin binds to this receptor on parietal cells.
Proton pump: The proton pump (H+/K+ ATPase) pumps H+ into the stomach lumen.

Inhibition of Gastric Acid Secretion

Cholinergic nerves: Release acetylcholine (ACh).
Muscarinic receptor: ACh binds to this receptor on parietal cells.
ECL cells: Secrete histamine.
Gastrin receptor: Gastrin binds to this receptor on ECL cells.
H2-receptor: Histamine binds to this receptor on parietal cells.
Gastrin receptor: Gastrin binds to this receptor on parietal cells.
Prostaglandin E2 (PGE2) receptor: Prostaglandins E2 and I2 bind to these receptors to suppress the secretion of gastric acid.
Somatostatin (SSR) receptor: Somatostatin binds to these receptors to inhibit HCl secretion.

Prostaglandins

Prostaglandins (E2 and I2) are lipids (eicosanoids) derived from arachidonic acid.
They are produced at locations of tissue damage or infection.
They are found in nearly all organs in the body.
They are involved in the healing process and control processes like inflammation and blood flow.
Their synthesis is catalysed by cyclooxygenase enzymes.

Drugs used to Treat Disorders of Acid Secretion

Antacids and alginates:
- Antacids buffer gastric acid, raising the gastric pH.
  - Examples are calcium carbonate and magnesium carbonate (Rennie).
- Alginates are anionic polysaccharides that form a viscous gel in water. They are often combined with antacids (Gaviscon) to treat acid reflux.
Histamine H2-receptor antagonists: Examples include cimetidine and ranitidine.

Answers to the Questions

Q1: How is the stomach protected from self-digestion? The stomach is protected by a mucosal barrier with several components. These include a thick coating of bicarbonate-rich mucus and the presence of tight junctions between epithelial cells which prevent gastric juice from penetrating the underlying tissue layers.
Q2: What is chyme? Chyme is a thick, semiliquid mass of partially digested food mixed with gastric secretions and enzymes.
Q3: What cells produce gastrin? Gastrin is produced by G cells in the antrum of the stomach.
Q4: What cells produce histamine? Histamine is produced by ECL cells in the gastric gland.
Q5: What is the name of this proton pump and how does it function? The proton pump is called H+/K+ ATPase. This pump carries out active transport using energy from ATP hydrolysis.
Q6: What cells produce Somatostatin? Somatostatin is produced by D cells in the gastric gland.

Stomach Physiology

The stomach performs both chemical and mechanical digestion.
It stores ingested food and mixes it with gastric secretions to form chyme.
Gastric juice, produced by the stomach, has a pH of 1-3.
It contains hydrochloric acid (HCl), electrolytes, mucus, water, and intrinsic factors.
The stomach secretes 2-3 liters of gastric juice per day.
The stomach is divided into four main regions: cardia, fundus, body, and pyloric part.
The Orad region is also known as the oxyntic gland area.
The Caudad region is known as the pyloric gland area.

Microscopic Histology of the Stomach

The stomach wall is composed of four layers: mucosa, submucosa, muscularis externa, and serosa.
Gastric pits extend into the mucosa as tubules, forming gastric glands.
Gastric glands contain four major types of secretory epithelial cells: parietal cells, neck cells, chief cells, and endocrine cells.
Parietal cells secrete HCl and intrinsic factor.
Neck cells secrete bicarbonate to buffer pH, mucus, and water.
Chief cells secrete digestive enzymes, primarily pepsinogen.
Endocrine cells secrete hormones such as gastrin, ghrelin, and somatostatin.

Innervation of the GI Tract

The GI tract is innervated by the autonomic nervous system, specifically the left and right vagus nerves.
There is both an extrinsic and an intrinsic component to the innervation.
The intrinsic component is called the enteric nervous system and contains two primary plexuses: the submucosal plexus and the myenteric plexus.
The submucosal plexus regulates gastric secretion, blood flow, and detects the nutritional composition of the bolus.
The myenteric plexus modulates tone and velocity of smooth muscle contractions.

Gastric Secretion

Parietal cells, primarily located in the proximal 80% of the stomach (oxyntic gland area) secrete HCl.
HCl converts pepsinogen to pepsin, provides an optimal pH environment for digestion, and destroys bacteria.
Intrinsic factor, also secreted by parietal cells, is crucial for the absorption of vitamin B12 in the small intestine.
Chief cells, located at the lower part of the gastric gland, secrete pepsinogen.
Pepsinogen is converted to the active enzyme pepsin in the acidic environment of the gastric lumen.

Endocrine Cells of the Stomach

G cells located in the antrum (pyloric gland area) secrete gastrin, a hormone that stimulates acid secretion, pepsinogen release, mucus production, HCO3- secretion, gastric motility, and inhibits gastric emptying.
D cells, located in the antrum and body of the stomach, secrete somatostatin, a polypeptide hormone that inhibits gastrin release and acid secretion.
ECL cells, scattered throughout the gastric mucosa, secrete histamine, which acts as a paracrine agent to stimulate acid secretion.

Mucus Secreting Cells

Mucus neck cells and surface mucus cells secrete mucus to protect the stomach lining from acid and enzymes.
Mucus forms a gel that protects the gastric mucosa from damage.
Mucus secreting cells also release bicarbonate (HCO3-) to buffer the pH.

The Mucosal Barrier

The mucosal barrier is formed by bicarbonate-rich mucus and the tight junctions between epithelial cells.
The mucosal barrier protects the stomach from autodigestion by preventing gastric juice from penetrating the underlying tissue layers.
Local irritation stimulates the production of prostaglandins (PGs), which increase mucus and HCO3- production and inhibit acid secretion.
The gastric lining has a high rate of cell division, ensuring rapid renewal of the mucosal barrier.

Consequences of Failure of the Mucosal Barrier

Breaching the gastric mucosal barrier leads to gastritis, an inflammation of the underlying tissue.
Persistent erosion of the gastric mucosa can result in the formation of gastric ulcers, a lesion in the gastric mucosa.

Gastric Motility

The stomach serves as a reservoir for food, fragments it into smaller particles, and controls the emptying of its contents into the duodenum.
Receptive relaxation allows the stomach to accommodate a large volume of food with minimal pressure increase.
The empty stomach has a volume of approximately 50 ml and is contracted with folded mucosa and submucosa.
During receptive relaxation, the smooth muscle cells in the orad region of the stomach relax.
The vagus nerve and the enteric nerve plexuses coordinate to release nitric oxide (NO) and serotonin, resulting in smooth muscle relaxation.
Mixing involves peristaltic waves that begin in the stomach body and move towards the antrum.
Strong antral contractions force contents back into the stomach body, known as retropulsion.
The muscularis of the stomach consists of two layers of smooth muscle: an inner circular layer and an outer longitudinal layer.
The muscularis also has an inner oblique smooth muscle layer enabling contraction in three directions.
Gastrointestinal motility depends on coordinated contractions of smooth muscle.
Slow waves are spontaneous cycles of depolarization and repolarization in smooth muscle cells.
The frequency of slow waves varies by region of the GI tract.
Gastric slow waves occur at a frequency of approximately 3 per minute.
The pacemaker zone generates the rhythm of gastric slow waves.
Slow waves do not induce contractions but coordinate them by controlling the appearance of action potentials.
Action potentials are triggered when the peak of a slow wave exceeds a certain threshold.
The intensity of the stimulus determines the number of action potentials fired.
Action potentials elicit muscle contraction and the number of action potentials determines the strength of the contraction.
Gastric emptying involves coordinated contractile activity of the stomach, pylorus, and proximal small intestine.
The pyloric sphincter is a smooth muscle and connective tissue ring between the gastric antrum and the duodenum.
It controls the rate of gastric emptying and prevents duodenal contents from regurgitating into the stomach.
The autonomic nervous system regulates the pyloric sphincter, with sympathetic nerve fibers increasing constriction and parasympathetic fibers relaxing it.
Hormones such as gastrin, cholecystokinin (CCK), gastric inhibitory peptide (GIP), and secretin constrict the sphincter.
The rate of gastric emptying is regulated by the nature of the duodenal contents.
Materials high in fat digestion products, acidic or very hypertonic, slow down gastric emptying.
Receptors in the duodenum and jejunum detect acidity, osmotic pressure, fats, amino acids, and peptides, triggering the release of intestinal hormones.
Intestinal hormones inhibit antral contractions and/or constrict the pyloric sphincter to slow down gastric emptying.

Interstitial cells of Cajal (ICC)

ICC are the pacemaker cells in the gut.
They generate and propagate slow waves in gastrointestinal muscles.
ICC activity determines the frequency of contractions in the stomach, intestine, and colon.

Hypertonic Material/Solution

A hypertonic solution has a higher concentration of solutes compared to another solution.
This means it has a lower water concentration.

Inflammation

The body's response to injury.
Rid the body of the initial cause of injury.
Break down cells damaged by injury.
Occurs as part of innate immunity.
The first line of defence.
Not a disease.
- Not always infection.

Beneficial effects of inflammation

Delivery of immune cells and proteins.
Dilution of toxins.
Eliminate substances and allow for tissue repair.
Can stimulate a further response.
Entry of drugs.

Inappropriate inflammation

Autoimmune disorders.
Excessive response: Sepsis.
Inadequate response: AIDS.

Causes of Inflammation

Infectious agents.
Chemicals.
Foreign bodies
Physical trauma.
Dead cells.
Allergens.

Types of Inflammation

Acute inflammation: immediate defense reaction of tissue to injury.
- Characterised by vascular and exudative processes.
Chronic inflammation: prolonged and persistent inflammation.
- May be a continuation of acute inflammation or result of an insidious insult.
- Characterised by scar tissue formation.

Acute Inflammation

Macroscopic features:
- Erythema (redness).
- Oedema (swelling).
- Warmth.
- Pain.
- Loss of function.
Microscopic features:
- Vascular changes:
  - Vasodilation.
  - Change in calibre and wall structure.
  - Increased blood flow.
- Exudative changes:
  - Increased permeability.
  - Movement of fluid, proteins and cells.
- Neutrophils:
  - Emigrate.
  - Accumulate.
  - Try to eliminate: phagocytosis.

Outcomes of Acute Inflammation

Resolution:
- Acute inflammatory response.
- Healing.
- Healthy tissue injury.
Persistence:
- Lytic enzymes.
- Accumulation of pus.
- Autoimmune disease.
- Death.

Chronic Inflammation

Prolonged duration.
Inflammation, injury, and repair co-exist.
Can continue from acute inflammation or develop insidiously.

Microscopic Features of Chronic Inflammation

New immune cells:
- Lymphocytes.
- Macrophages.
Tissue destruction.
Attempts at healing.
Involves adaptive immunity.

Adaptive Immunity

T lymphocytes.
- TH: helper.
- TC: cytotoxic.
B lymphocytes.
- Plasma cells.

Other Mediators of Chronic Inflammation

Monocytes/macrophages.
Interleukins.
Acute phase proteins.
Complement.

Leukocytosis

Elevated white blood cell count.

Patient Example 1

45 year old gentleman.
WBC count: 13.

Patient Example 2

89 year old lady with dementia.
WBC count: 22.
Neutrophil count: 18.

Cell Injury and Cell Death

Cells can adapt to stress by adjusting size, number, or function.
When stress exceeds the cell's ability to adapt, cell injury occurs.
Cell injury can be reversible if the stimulus is minor and transient.
Severe and progressive cell injury leads to cell death.
Cell death can occur through apoptosis or necrosis.

Causes of Cell Injury

Oxygen deprivation (Hypoxia): Impairs aerobic metabolism and can result from various factors, including altitude sickness or anemia.
Ischemia: Local or systemic blood supply issues causing a loss of oxygen, nutrients, and accumulation of toxins. It is worse than hypoxia due to the combined effects.
Physical Agents: Heat or cold can disrupt protein structure and metabolic pathways, leading to cell damage.
Electrical Injuries: Direct damage to cells caused by current flow.
Chemicals: Chemicals can damage cells directly or indirectly through metabolic breakdown products.
Infectious Agents: Viruses, bacteria, fungi, and prions can disrupt cellular function.
Immune Reactions: Hypersensitivity reactions can cause cell damage.
Nutritional Imbalances: Deficiencies or excesses of vitamins or other nutrients can lead to cell injury.

Oxygen Deprivation

Hypoxia refers to oxygen deprivation, which impairs aerobic metabolism.
Ischemia is a type of hypoxia caused by reduced blood flow.
Ischemia is more severe than hypoxia due to the loss of nutrients and accumulation of toxins.

Physical Agents

Heat can cause protein coagulation and breakdown, cell necrosis, skin disruption, and water loss.
Cold can lead to ischemia due to vasoconstriction, ice crystal formation, and coagulation.
Electrical injuries cause direct damage to cells, particularly along the path of least resistance.

Chemicals

Chemicals can damage cells directly or indirectly through metabolic breakdown products.
Chemical damage can disrupt osmotic balance, biochemical reactions, and cell membrane integrity.
Corrosive substances like acids and bases cause direct injury by denaturing proteins and disrupting cell structures.

Infections

Infections can cause cell damage directly or indirectly.
Viruses can subvert cellular machinery to produce new viral particles.
Bacteria can release toxins, directly lyse cells, or trigger an inflammatory response.

Immune Reactions

Allergies (hypersensitivity reactions) can trigger inflammation and cell damage.

Nutrition

Nutritional deficiencies can lead to cell injury, as seen in scurvy (vitamin C deficiency).
Nutritional excesses can also be harmful, as in vitamin A toxicity or obesity.

Cell Death

Apoptosis: Programmed cell death, characterized by internally controlled nuclear dissolution.
- Physiological: Embryogenesis, involution of hormone-dependent tissue, elimination of harmful lymphocytes, cell loss in proliferating populations.
- Pathological: Cells with DNA damage, cells with endoplasmic reticulum stress, certain infections.
Necrosis: Uncontrolled cell death caused by enzymatic cell digestion and leakage of cell contents.
- Always pathological.

Types of Necrosis

Coagulative: Cell structure remains visible despite non-vitality. Characteristic of ischemic injuries (except in the brain).
Liquefactive: Tissue is replaced by liquefied material due to enzymatic digestion. Common in infections and brain ischemia.
Caseous: Tissue has a cheese-like appearance. Associated with tuberculosis.
Gangrenous: Necrosis of a limb, often involving coagulative and, in some cases, liquefactive necrosis.
Fat: Necrosis of adipocytes, often seen in pancreatitis and breast disease.
Fibrinoid: Immune-mediated necrosis of vessel walls caused by deposition of antigen-antibody complexes and fibrin.

Key Terms

Hyperplasia: Increase in the number of cells.
Hypertrophy: Increase in cell size.
Atrophy: Decrease in cell size.
Metaplasia: Reversible change of one cell type to another.
Dysplasia: Abnormal cell growth and development.
**Neoplasia:**Abnormal growth of tissue (tumor).

Cellular Adaptation

Cellular adaptation is a reversible change in cells due to environmental changes.
This happens in physiological and pathological conditions.
Adaptation is an attempt to preserve cell vitality.
Adaptation involves changes in:
- Cell number
- Cell size
- Cell type

Proliferative Capacity of Cells

Three types: labile, stable, and permanent.
Labile cells:
- Continuously divide in adult life.
- Dividing cells are exposed to external environments, experiencing wear and tear.
Stable cells:
- Infrequent divisions but can divide rapidly if needed.
- They are mainly quiescent.
Permanent cells:
- Never divide in adult life.
- These are terminally differentiated cells.
- Some cells divide, but not to a clinically significant level.

Hyperplasia

An increase in the number of cells in a tissue.
This occurs in labile and stable cells (not permanent).

### Physiological Hyperplasia

Hormonal:
- Example: Endometrium.
Compensatory:
- Example: Partial hepatectomy.

### Pathological Hyperplasia

Causes:
- Excessive hormone or growth factor stimulation.
- Chronic irritation.
Increased risk of tumor development due to dysregulation of proliferation.
This can occur alongside hypertrophy.

### Hypertrophy

An increase in cell size.
This can happen in any cell type.
It is common in permanent cells experiencing increased demands.
Increased demands mean more structural proteins are produced to meet the demands, not just swelling.

### Physiological Hypertrophy

Increased functional demand:
- Example: Skeletal muscle.
Hormonal or growth factor:
- Example: Uterine muscle during pregnancy, often combined with hyperplasia.

### Pathological Hypertrophy

Increased functional demand:
- Example: Cardiac muscle.
Left ventricle hypertrophy is common in hypertension and aortic stenosis.

Atrophy

Shrinkage in cell size by loss of cell substance.
This involves the self-digestion of organelles, known as autophagy.
Reduced organ size due to cell loss is referred to as involution.

### Causes of Atrophy

Reduced workload.
Loss of nerve supply.
Reduced blood supply.
Inadequate nutrition.
Loss of endocrine stimulation.
Ageing.

Metaplasia

A reversible change where one adult cell type is replaced by another.

### Physiological Metaplasia

This occurs during normal growth and development.
Example: Glandular to squamous epithelium in the cervix due to vaginal acidity.

### Pathological Metaplasia

An abnormal environment triggers an adaptive response.
Example: Squamous to glandular epithelium in reflux oesophagitis.

Small Intestine Physiology & Secretion

The small intestine is the longest GI tract organ, about 7 meters long, with a diameter of 3 to 4 cm, providing a large absorptive surface area of 4500 m².
It is divided into three segments: duodenum, jejunum, and ileum.
The duodenum is the shortest segment (28 cm) where most digestion occurs, receiving digestive content from the stomach, pancreatic juice, and bile.
The jejunum comprises two-fifths of the small intestine and is the main site of absorption.
Digestion is the breakdown of ingested molecules into smaller ones by digestive enzymes, either secreted into the GI tract lumen or present on the luminal surface.
Absorption is the process where molecules are transported through epithelial cells lining the GI tract and enter the blood or lymphatic system.
The mucosa of the small intestine is arranged in plicae circulars, about 800 in the small intestine.
Brunner's glands in the duodenum secrete mucus, a rich alkaline fluid, to protect the small intestine from acidity and enzymes.
The small intestine wall secretes about 1.5 L of water into its lumen to correct chyme hypertonicity and facilitate ion secretion, followed by water flow by osmosis.
Overall, there is a net absorption of water from the small intestines, including salivary, gastric, hepatic, and pancreatic secretions, as well as ingested water.

Small Intestine Hormones

Motilin stimulates migrating motor complexes (MMCs) through the enteric and autonomic nervous system.
MMCs are interdigestive motility patterns, distinct from gastric motility, occurring between meals to sweep the GI tract of indigestible debris.
Vasoactive Intestinal Peptide (VIP) increases blood flow to the GI tract.
Gastric Inhibitory Peptide (GIP), discussed in a previous session, inhibits gastric secretion and stimulates insulin secretion.
Cholecystokinin (CCK) and Secretin, also covered in the previous session, inhibit gastric motility and secretion, and work together to control pancreatic and biliary secretions from the liver.

Pancreatic and Biliary Secretions

The exocrine pancreas and liver secrete substances via ducts into the small intestine.
Secretin stimulates the pancreas to release bicarbonate ions into the duodenum and the liver to release bile into the gallbladder.
CCK stimulates the pancreas to release digestive enzymes into the duodenum and the gallbladder to contract and release bile into the duodenum.

Nutrient Absorption

The figure shows where nutrients (carbohydrates, proteins, lipids, minerals, vitamins, and water) are absorbed along the GI tract.
Most nutrient breakdown happens in the GI tract lumen by secretions from the stomach and pancreas.
Enterocytes, the absorptive cells of the intestine, possess a large surface area with brush borders (microvilli) on their apical membrane.
Additional nutrient breakdown occurs at the brush borders, such as for small peptides, disaccharides, and triglycerides.
These molecules enter cells via transporters on the brush border and exit through the basolateral membrane to enter the blood circulation.

Digestion and Absorption of Fats

Fats are broken down and absorbed entirely in the small intestine.
Pancreatic lipase is the main enzyme involved.
Gastric acid and stomach mixing break down dietary fats into small particles that are delivered to the duodenum.
In the duodenum, fats are mixed with emulsifying agents (bile salts and phospholipids) from the liver, which form clusters around triglycerides and create emulsion droplets.

Pancreatic Secretion

The pancreas has exocrine and endocrine functions.
It weighs less than 100 g but secretes about 1 L of pancreatic juice, ten times its mass.
Pancreatic juice is composed of alkali (aqueous solution rich in bicarbonate ions secreted by duct cells) and a complex mixture of digestive enzymes secreted by acinar cells.
Alkali neutralizes the acidity of chyme from the stomach, preventing inactivation of pancreatic enzymes in the small intestine.
Enzymes include:
- Pancreatic amylase for starch breakdown
- Pancreatic lipase for fat digestion
- Peptides (trypsin, chymotrypsin, carboxypeptidase) for protein digestion, secreted in inactive precursor forms.

Activation of Pancreatic Enzyme Precursors

Enzymes secreted by acinar cells in their precursor form are called zymogens and are activated in the duodenum.
Enterokinase, a proteolytic enzyme embedded in the luminal plasma membrane of intestinal epithelial cells, activates zymogens by splitting a peptide, releasing the active form.
Trypsin, once activated by enterokinase, also acts as a proteolytic enzyme to activate other zymogens.
Trypsin's other function is digesting ingested proteins and peptides.

Bicarbonate Secretion from Pancreatic Duct Cells

The mechanism of bicarbonate secretion into the pancreatic duct lumen is similar to acid secretion in the stomach, but the direction of hydrogen and bicarbonate ions is reversed.
Carbonic anhydrase in the cytosol of duct cells converts water and carbon dioxide into hydrogen and bicarbonate ions.
Hydrogen ions are actively transported across the basolateral membrane and absorbed into the blood.
Bicarbonate ions are secreted into the pancreatic duct lumen.

Control of Pancreatic Secretions

Pancreatic enzyme and alkali secretion are controlled separately.
Acinar cell enzyme secretion is regulated by:
- CCK (intestinal hormone)
- Acetylcholine (neurotransmitter released by the vagus nerve)
Vagus nerve activity is triggered by taste and smell of food (vegal reflex) and signals from the stomach.

Prevalence

Prevalence is a measure of how common a disease is at a specific time.
Prevalence can be expressed as a percentage, or a number per "n" people.
Point prevalence is the proportion of individuals with the condition at a specific point in time.
Period prevalence is the proportion of individuals with the condition at any time during a specified time interval.
Lifetime prevalence is the proportion of individuals with the condition at any point in their lives.
Prevalence is usually referring to "point prevalence" if not specified otherwise.

Calculating Prevalence

The numerator is the number of people with the condition.
The denominator is the total number of people in the population.
It is often presented as a rate "per 1000", "per 100,000", etc. when prevalence is low.

The use of prevalence

Prevalence is used to gauge the burden of disease in the population.
Prevalence can be affected by disease duration.

Incidence

Incidence is the rate at which new cases occur in a population over a defined period of time.
It can be expressed as cases per "n" people per time period, or cases per "n" person-years.
Person-years are a combination of the number of people observed and the number of years they were observed for.

Calculating Incidence

Numerator: number of new cases.
Denominator: number of people * years observed.

Relating Incidence and Prevalence

High incidence and high prevalence indicate a common condition that is not brief.
Low incidence and high prevalence indicate an uncommon condition that is long-term.
High incidence and low prevalence indicate a common condition that is very brief.
Low incidence and low prevalence indicate an uncommon condition that is short-term.

Factors Affecting Prevalence

The factors that affect prevalence include incidence rate, recovery rate, death rate and migration rate.
These factors can be visualized as an "epidemiologist's bathtub":
- Water flowing into the tub represents incidence.
- Water draining from the tub represents death, recovery, or migration.

Statistical Inference

Statistical inference is the process of drawing conclusions about a population based on a sample.
We take a sample and use it to make a best guess about the population.
The point estimation represents the best guess based on the sample data.

Conclusion

These concepts provide valuable tools for understanding the health of a population.
We can use these measures to track disease patterns, identify areas for intervention, and assess the effectiveness of public health programs.

ICD-10 Chapters

ICD-10 is a system for classifying diseases, it is used worldwide
There are 22 chapters in ICD-10

Chapter IV - Endocrine, nutritional and metabolic diseases

This chapter focuses on disorders related to hormones, nutrition, and metabolism
It includes blocks for thyroid gland disorders, diabetes mellitus, other endocrine gland disorders, malnutrition, nutritional deficiencies, obesity, and metabolic disorders

Diabetes Mellitus

ICD-10 codes E10 to E14 are used for diabetes mellitus
The codes further break down by type of diabetes (e.g., insulin-dependent, non-insulin-dependent) and complications
The fourth character within the diabetes code represents the presence of complications (e.g., coma, ketoacidosis, complications)

Hospital Episode Statistics (HES)

HES records all admissions, outpatient visits, and A&E visits to NHS hospitals in England
The data includes personal information, clinical information (diagnoses and operations), administrative data, and geographical information
HES data is used by commissioning and provider organisations, as well as researchers
It supports local service planning, identifies health trends, and helps ensure fair access to healthcare

Data Coding Systems

Two main clinical coding systems used in HES:
- ICD-10 (International Classification of Diseases, 10th Revision) used for diagnoses.
- OPCS-4 (OPCS Classification of Surgical Operations and Procedures, 4th Revision) used for surgical procedures.

Sources of Health Information

Multiple sources are used for assessing population health.
There is no single perfect source of data

Mortality Data

Previously covered in the text, strengths and weaknesses of mortality data were discussed

Morbidity Data

Cancer Registration System: used to track cancer diagnoses, treatment, and outcomes.
Hospital Episode Statistics (HES): records all hospital admissions, outpatient visits, and A&E visits.
Quality and Outcomes Framework (QoF): measures the quality of care provided by GPs and other healthcare professionals.
Notifications of Infectious Diseases: used to track the incidence of infectious diseases.

Cancer Registration

National Cancer Registration and Analysis Service (NCRAS) is responsible for collecting and analyzing data on cancer.
Data includes personal details, diagnosis, treatment, and outcomes
This data is used for monitoring cancer rates, evaluating cancer treatment, and supporting cancer research

Breast Cancer Incidence and Mortality

Data in the text shows trends in breast cancer incidence and mortality in the UK from 1975 to 2011.
This data highlights the impact of the 1988 screening programme.

Hospital Episode Statistics (HES)

HES is a comprehensive database containing information on all admissions, out-patient and A&E visits to NHS hospitals in England.
The data includes personal information, clinical information, administrative data, and geographical information.
HES data supports local service planning, identifies health trends, and ensures fair access to healthcare.

Data Coding Systems

ICD-10 is a system used to code diagnoses.
OPCS-4 is a system used to code surgical procedures.

Objective 2 Summary

The UK uses a variety of data sources to track health and disease.
Each source has its strengths and weaknesses.
Significant data coding systems are used in healthcare.

Self Assessment Questions

Prevalence of diabetes: tracked through the Quality and Outcomes Framework (QoF) or the Health Survey for England.
Cancer survival: monitored by the National Cancer Registration and Analysis Service.
Hospital admissions: recorded in the Hospital Episode Statistics (HES).
Surgical procedures: coded using OPCS-4.
The medical condition treated: coded using ICD-10.

Strengths and Weaknesses of Mortality Data

Strengths: complete coverage of deaths and births in the UK.
Weaknesses: accuracy can be uncertain due to diagnostic uncertainty, coding issues, and variable quality. Ethnicity is not collected.

Patient with Suspected Malaria

After appropriate clinical management, the next step is to report the suspected case to public health authorities.

Demography in the UK

Demography is the study of population size, structure, distribution, and development.
Key demographic metrics include population size, distribution, birth and death rates, life expectancy, and migration.
Reliable demographic statistics are essential for service planning and delivery.

Sources of Demographic Information

UK Census is a simultaneous recording of demographic data by the government at a particular time for all persons living in a specific territory.
- Conducted every 10 years since 1841 by the Office for National Statistics (ONS) in England and Wales.
- It is a legal requirement to participate.
- It is the most complete source of population information, with 98% coverage.
- Low enumeration groups (e.g., homeless individuals) exist, impacting accuracy.
- Census quality is assessed through coverage surveys and quality surveys (interviews).
- 2011 Census cost £480 million with online and postal completion.
- The UK population was 63.2 million in 2011.
- Shift towards online participation in the 2021 Census.
- Potential future shift towards administrative data (collected by government agencies).
- Data collected includes demographic, cultural, and socioeconomic information, as well as health data.

Birth Registration

Records live births in England and Wales.
Key source for population and mortality data.
Provides information about age, place of death, and cause of death.
Referred to the coroner if:
- Death is sudden or unexpected.
- The deceased is under 18 years old.
- The cause of death is unknown.
Informant (usually relative) notifies local Registrar within 5 days.

Death Registration

Records deaths in England and Wales.
Medical certificates of cause of death are issued by a doctor.
Coroners’ certificates are issued if death is referred to the coroner.
Records are coded using the ICD-10 system.
Data is collected by the Office for National Statistics (ONS).
Information is used to track mortality trends and plan public health interventions.

Underlying Cause of Death

This is the disease or injury that initiated the train of events leading to death.
The underlying cause of death is a key factor in mortality statistics and public health planning.

Population Estimates & Projections

Use census data and birth/death registration data to create estimates of the current population and project future population trends.

'CART' for Assessing Quality of Health Information

Completeness - the extent to which data is collected for all relevant cases.
Accuracy - the extent to which data reflects reality.
Representativeness / Relevance - the extent to which the data is relevant to the population being studied.
Timeliness - the extent to which data is collected and made available in a timely manner
Accessibility - how easily data can be accessed by users.

Strengths & Weaknesses of UK Census

Strengths:
- High completeness – 98% coverage.
- Accurate data – quality checks are in place.
- Provides representative data for various levels of population from individuals to the whole country.
Weaknesses:
- Low enumeration of some groups.
- Self-reported data – some inaccuracies can occur.
- Data is collected every 10 years, requiring time for processing and release.

Informed consent: A cornerstone of protecting individual rights and interests
Justification for consent: Ensures actions are legally and ethically permissible, lack of consent can lead to charges of assault or battery
Autonomy: The principle of self-rule, free from external control, crucial in bioethics
Informed consent: A requirement for medical treatment, investigations, examinations, disclosure of information, research, and education

Legal & Ethical Framework

Battery: Legal concept where lack of valid consent can lead to charges
GMC Guidance on Consent: Encourages a proportional approach, emphasizes practicality and judgment
Valid Consent Components: Competence/Capacity, Information, and Voluntariness

Capacity

Specific assessment for the specific decision at hand
Inability to make a decision: Not understanding information, not retaining information, not using/weighing information, or not communicating decision
Every adult is presumed capable: Avoid assumptions based on age, disability, or communication difficulties, offer support for decision-making
Capacity Fluctuates: Can be decision-dependent and changes with time
Special Considerations: Adults lacking capacity and children require specific accommodations

Information

Purpose: Informed consent ensures patients understand their options, not just relying on doctor's expertise
Tailored Information: Based on individual patient needs and situation
Important Information: Diagnosis/prognosis (including uncertainties), available treatment options (including doing nothing), nature of each option, desired outcomes, potential benefits, harms, and likelihood of success, etc.
Doctor's Responsibility: Not to assume what information is needed, how patients weigh information, or what outcomes are valued

Montgomery v Lanarkshire

Landmark Case: Established patient's right to information about material risks
Material Risk: Anything a reasonable person in the patient's position would likely find significant OR anything the doctor knows the patient would likely find significant
Patient as an Active Participant: Informed consent is not just about conveying information but engages patients in a dialog to make informed decisions

Voluntariness

Requirement: Consent needs to be given freely, no coercion
External Pressures: Seek out potential pressure from employers, family, insurers
Recognizing Coercion: Explicit coercion, implicit coercion, power differentials, family pressure
Patient's Right to Independent Decision: Facilitate conversations away from external influences

Implied Consent: Compliance with procedures (e.g., rolling up sleeve for blood pressure)
Oral Consent: Suitable for low-risk procedures or treatments
Written Consent: Typically for complex or high-risk interventions, significant consequences for patient's life (social, personal, or employment), non-primary care-related procedures, research participation, and legally required situations (e.g., fertility treatment).

Evidence, Not Guarantee: A signed consent form does not automatically represent valid informed consent
Valid Consent Requirements: Capacity, sufficient information provision, and voluntariness must still be met
Documenting the Conversation: While a signed form is evidence, documenting key aspects of the consent discussion is crucial

Responsibility: The doctor conducting the investigation/treatment should generally discuss the procedure with the patient.
Delegation Criteria: If delegation is necessary, the delegate must be: suitably trained and competent, knowledgeable about the intervention (benefits, harms, alternatives), skilled in communication, and competent to carry out the task with understanding of referral procedures

Responsibility: The person taking the history and using the information is responsible for obtaining consent

Poor Information/Time Pressure: Adequate information provision and alternative sources of information (team members, booklets)
Feeling Rushed: Time and space for patients to decide
External Pressure: Talk to the patient independently, identify and address any pressure

Emergency Situations

Treatment Without Consent: Permitted if it is immediately necessary to save a life or prevent serious deterioration, see specific guidance for details.

Language Barriers

Translated Information: Do not solely rely on English-speaking relatives as interpreters, ensure accurate translation.

Summary

Consent: A fundamental pillar of ethical medical practice
Beyond Signature: Consent goes beyond a signature and involves strict requirements
Individualized Approach: Each situation demands specific considerations

Drugs to Treat Disorders of Acid Secretion

Antacids counter stomach acidity by buffering gastric acid, raising the gastric pH to levels that are less harmful.
- Key examples: Aluminum hydroxide and magnesium hydroxide, Calcium carbonate and magnesium carbonate.
Alginates are anionic polysaccharides that form a viscous gel when they bind water.
- Often combined with antacids.
- Key example: Sodium alginate.
Physiology of acid secretion:
- Gastrin, histamine and acetylcholine stimulate acid secretion from parietal cells in the stomach.
- Somatostatin inhibits acid secretion.
Histamine H2-receptor antagonists competitively inhibit histamine actions at H₂-receptors.
- Key example: Famotidine.
- Decrease both basal and stimulated acid secretion.
Proton pump inhibitors irreversibly inhibit the H⁺/K⁺-ATPase pump, the final step in the acid secretory pathway.
- Key examples: Omeprazole, Lansoprazole.
- Are more effective than H₂-receptor antagonists.
- Are inactive at neutral pH.
- They accumulate in secretory canaliculi and are activated in an acidic environment, making them very specific.
- A single dose can affect acid secretion for 2-3 days.
Common conditions requiring drug treatment for excess acid secretion:
- Reflux oesophagitis
- Peptic ulcer
- Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs)
- H. Pylori infection
Reflux oesophagitis is inflammation of the lower oesophagus caused by persistent episodes of reflux.
- Symptoms: Heartburn, Regurgitation, Haematemesis.
- Complications: Oesophageal ulceration, Peptic stricture, Barrett’s oesophagus.
- Treatment: Antacids, alginates, H₂-receptor antagonists and proton pump inhibitors.
NSAIDs impair the renewal of the gastric mucosal barrier by interfering with prostaglandin production.
- Prostaglandin E2 stimulates the renewal of the gastric mucosal barrier by:
  - Stimulating gastric mucus production
  - Stimulating bicarbonate secretion
  - Inhibiting gastric acid production
  - Promoting local stomach tissue repair
NSAIDS inhibit prostaglandin synthesis by inhibiting cyclooxygenase (COX) enzymes.
Helicobacter Pylori damages stomach and duodenal tissue.
- It secretes urease, which breaks down urea into CO₂ and NH₃.
- NH₃ neutralises gastric acid.
- H. Pylori penetrates the mucus barrier, allowing acid to penetrate the tissues.
- NH₃, other bacterial products, and acid damage epithelial cells.
Treatment of H. Pylori infection:
- Antibiotics (e.g. Amoxicillin with Clarithromycin) and a proton pump inhibitor such as Lansoprazole.
- Eradication of H. Pylori can produce long-term remission of ulcers.

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Explore the intricacies of gastric secretion and acid production in this quiz. Learn about the components of gastric juice, the role of parietal cells, and how hydrochloric acid is produced and regulated within the stomach. Test your understanding of these essential digestive processes.