IMED3111 Integrated Medical Systems 2025: SGL2 - Basic Pathological Processes Notes

IMED3111 Integrated Medical Systems 2025: SGL2 - Basic Pathological Processes

General Information

• Specimens can be viewed in PELC, searching by the four digits after 'M'.
• Histories provided are for exploring pathological concepts, not specific diseases.
• Specific patient histories are generally available on PELC.
• A post-workshop version of the worksheet will be available on LMS after the tutorial sessions, as a guide to answers.
• Specimens demonstrate necrosis, hyperplasia, hypertrophy, acute and chronic inflammation, healing and repair, developmental anomalies, environment/toxins, and specific lesions like ulceration.

General Aims

1. Consolidate theoretical knowledge from lectures and personal study.
2. Put knowledge into a clinical and population-wide context.
3. Develop generic skills for clinical medicine: describing, synthesizing, discussing, and prioritizing information for diagnosis and patient management.
4. Learn from peers and teaching staff in smaller groups.

Case 1: LUNG - Lobar Pneumonia (T28.M4062/7)

• Process: Acute inflammation.
• Patient: 75-year-old smoker with fever and cough.
• Physical examination: Dullness to percussion over the affected lung lobe.
• Chest x-ray: Increased opacity (whiter appearance) of the affected lobe.
• Blood tests: Increased neutrophil count, elevated CRP and ESR.
• Sputum culture: Gram-positive diplococci.

Observations:

• Normal lobe: Tan/red, spongy, and air-filled.
• Abnormal lobe: Solid and pale; diffusely affected.

Pathological Processes:

• Lobar pneumonia is acute inflammation of a lung lobe, usually due to bacterial infection.
• Main inflammatory cell: Neutrophils.

X-ray Appearance:

• The affected lung tissue appears white on x-ray due to the influx of fluid and cells during the acute inflammatory response, making the tissue denser than normal, air-filled lung tissue.

Anthracosis:

• Dark black patches in the lung and lymph nodes.
• Cause: Inhalation of carbon due to pollution and/or smoking.

Other Environmental/Toxic Agents Affecting the Lung:

• Cigarette smoke, asbestos, silica (from mining or stone benchtop manufacture), coal dust (occupational due to mining), radiation, noxious gases like mustard gas/ricin.

Case 2: LUNG - Miliary Tuberculosis (T28.M4409/13)

• Process: Chronic/Granulomatous inflammation.

Observations:

• Numerous small tan/white nodules (1-3mm) scattered throughout the lung parenchyma in a miliary pattern.
• Patient presented with morning fevers, malaise, coughing, and enlarged lymph nodes.
• Post-mortem diagnosis: Miliary tuberculosis.
• Microscopically: Each nodule is a small granuloma.

Granulomatous Inflammation:

• A type of chronic inflammation characterized by collections of activated macrophages, often with T lymphocytes, and sometimes associated with central necrosis.
• Forms in response to agents difficult to eradicate.

Necrotizing vs. Non-Necrotizing Granulomas:

• The presence or absence of necrosis can be a clue to the aetiology.
• Tuberculosis: Classic cause of necrotizing granulomas, also seen with fungal infections. Hypoxia and free radical-mediated injury lead to necrosis.
• Caseous necrosis: Necrotizing granulomas with cottage cheese-like appearance macroscopically.
• Non-necrotizing granulomatous inflammation: Sarcoidosis, Crohn’s disease, foreign body type granulomas.

Microscopic Appearance of a Granuloma:

• Collection of activated macrophages.
• Macrophage activation: Enlargement and flattening of cells (epithelioid appearance).
• Multinucleated giant cells may form from fused macrophages.
• Rim of small lymphocytes may be present.
• Central zone of necrosis may or may not be present.

Case 3: APPENDIX - Acute Appendicitis (T66.M4101/8)

• Process: Acute inflammation and the acute phase reaction.
• Patient: Young man with reduced appetite, fever, and right lower quadrant pain.
• Diagnosis: Acute appendicitis.

Observations:

• Tip of the appendix: Dusky red/brown with a creamy yellow exudate on the serosal surface.
• Exudate: Protein-rich fluid containing acute inflammatory cells (neutrophils), fibrin, macrophages, and sometimes bacteria.

Five Steps of a Typical Acute Inflammatory Reaction:

1. Recognition of the offending agent by host cells and molecules in extravascular tissues.
2. Recruitment of leukocytes and plasma proteins from the circulation to the site of the offending agent.
3. Activation of leukocytes and proteins to destroy and eliminate the offending substance.
4. Control and termination of the reaction.
5. Repair of damaged tissue, or fibrosis/scarring.

Fever Mechanism:

• Neutrophils and macrophages secrete substances (IL-1 and TNF-alpha) into the bloodstream.
• IL-1 and TNF-alpha affect vascular receptors in the thermoregulatory area of the hypothalamus.
• This induces local prostaglandin production, activating the sympathetic nervous system and causing fever.

Important Mediators of Acute Inflammation and Their Effects:

• Histamine
  • Dilation of arterioles and increased vessel permeability via H1 receptors
  • Increased heart rate via H2 receptors
• Arachidonic acid metabolites (prostaglandins and leukotrienes)
  • Prostaglandins: Vasodilation, increased vascular permeability, white cell migration, and fever
  • Leukotrienes: Bronchoconstriction and encourage eosinophil migration
• Complement
  • Membrane attack by rupturing the cell wall of bacteria.
  • Phagocytosis by opsonizing antigens. C3b has the most important opsonizing activity
  • Chemotaxis for macrophages and neutrophils.
  • Triggers liver to produce acute phase reactants
  • Fever
• TNF alpha and IL-1

Case 4: GALLBLADDER - Chronic Cholecystitis (T57.M3100/4)

• Process: Chronic inflammation.
• Patient: Long history of episodes of biliary colic.
• Diagnosis: Chronic cholecystitis.

Observations:

• Gallbladder with a markedly thickened wall and erosion/ulceration of the mucosa.
• Some examples contain gallstones of varying colours and types.

Chronic Inflammation:

• An inflammatory response of prolonged duration in which inflammation, tissue injury, and attempts at repair coexist.
• Predominant cells: Macrophages and lymphocytes.

Ways Chronic Inflammation Can Arise:

• When acute inflammation cannot get rid of the infection or repair tissue damage.
• Due to autoimmune diseases.
• Due to prolonged exposure to toxins.

Case 5: HEART SLICE - Left Ventricular Hypertrophy (T33.M7200/1)

• Process: Hypertrophy.
• Patient: Long history of uncontrolled hypertension (high blood pressure).

Observations:

• Normal heart: Rounded left ventricle and crescent-shaped right ventricle. Normal wall thickness: approximately 8mm LV, 5mm RV, and 8mm septum.
• Left ventricular hypertrophy: Markedly thickened left ventricle with a narrowing of the cavity.

Hyperplasia vs. Hypertrophy:

• Hyperplasia: An increase in the NUMBER of cells.
• Hypertrophy: An increase in the SIZE of each cell.
• Macroscopic specimen appearance: Both processes lead to organ enlargement.
• Each tissue type has an underlying propensity to undergo either hyperplasia or hypertrophy in response to physiological or pathological processes.

Case 6: BLADDER AND PROSTATE - Benign Prostatic Hyperplasia/Hypertrophy (BPH) and Secondary Bladder Wall Hypertrophy (T77.M8140/2)

• Process: Hyperplasia and Hypertrophy.
• Patient: Elderly gentleman with urinary obstruction after a long history of urinary retention due to an enlarged prostate.
• Normal prostate size: Walnut or golf ball (about 20g).
• Normal bladder wall thickness: Around 5mm.

Observations:

• Prostate: Enlarged to 3 or 4 times its normal size.
• Bladder wall: Thickened and trabeculated.
• Urethra passes through the prostate, so enlargement can cause difficulty urinating, leading to bladder wall hypertrophy.

Hyperplasia vs. Hypertrophy:

• Hyperplasia: An increase in the NUMBER of cells.
• Hypertrophy: An increase in the SIZE of each cell.
• Prostate BPH: Both hyperplasia and hypertrophy occur simultaneously.

Case 7: SMALL INTESTINE - Ischaemia, Infarction/Necrosis

• Process: Ischaemia, infarction/necrosis
• Patient: Lady presented with symptoms of small bowel obstruction with multiple abdominal surgeries in the past

Observations:

• Twisted portion of small intestine with affected zone appearing dark red to black (swollen)
• Unaffected bowel is light tan in color.

Patient Presentation:

• Abdominal pain, diarrhea, nausea, and vomiting as well as blood in stool, abdominal bloating, and tenderness.

Complications:

• Infarction of the bowel, perforation, peritonitis, or scarring.

Definitions:

• Necrosis: A form of cell death caused by non-survivable injury and is non-programmed.
• Ischaemia: Results from reduced blood flow to tissues (which results in tissue hypoxia and build up of toxic metabolites).
• Infarction: Necrosis due to ischaemia.

Differences between Apoptosis and Necrosis:

Other Causes of Necrosis:

• Entrapment or twisting.
• External compression (tumour).
• Wall thickness expansion of the vessels (atherosclerosis).
• Material lodging inside the vascular lumen (thrombus).
• Low blood pressure reducing overall blood flow.

Case 8: SMALL INTESTINE (Y SHAPED SPECIMEN) - Meckel’s Diverticulum (T65.M2337/7)

• Process: Developmental anomaly.
• Patient: Little boy presented with gastrointestinal bleeding.
• Diagnosis: Meckel’s diverticulum, a common congenital anomaly that occurs when the vitelline duct is not fully resorbed as a foetus.

Patient Presentation:

• Many people remain asymptomatic.
• Gastrointestinal bleeding, abdominal pain, nausea, vomiting from obstruction, or inflammation.

Case 9: SKIN - Acute Inflammation, Wound Healing, Ulceration (T01.M4003/1)

• Process: Acute inflammation, wound healing, ulceration.
• Patient: Elderly patient in a nursing home presented with skin ulcers to the heels and over the sacrum.

Observations:

• Punched-out defect in the skin surface with a full-thickness defect through the skin, exposing underlying soft tissues and fat (and in some specimens, bone).

Definition of an Ulcer:

• A full-thickness defect in an epithelial surface (e.g., skin, gut, mucous membrane).

Erosion vs. Ulcer:

• Erosions: Superficial lesions where the epithelium is partially lost. They heal WITHOUT scarring because they are not full-thickness defects. An erosion in the skin does not extend into the dermis so can re-epithelialize without a scar forming.

Wound Healing:

• Primary intention: Wounds closed surgically heal with a small scar; closest skin can get to regeneration (perfect regeneration only possible in certain organs like bone and liver).
• Secondary intention: Large deep ulcers.
• Both primary and secondary intention wound healing form scar tissue.
• Proliferative phase: Creation of collagen by fibroblasts to replace the lost tissue.

Case 10: LIVER - Cyst

• Process: Showcase an example of a true cyst vs pseudocyst
• Patient: Incidental cyst found post-mortem for unrelated cases

Observations:

• Cut surface fo the liver shows a sigle well circumscribed cyst that contains white and red nodular material (some may contain background metastatic deposits of cancer)

Definition of a Cyst:

• A pathological cavity filled with fluid.

Cyst vs. Pseudocyst vs. Abscess:

• True cyst: Lined by epithelium.
• Pseudocyst: Cavity containing fluid that is not lined by epithelium.
• Abscess: A specific type of pseudocyst caused by infection, where the fluid within the cyst is pus (viable and dead microorganisms, viable and degenerate neutrophils, extracellular fluid).

Case 11: LIVER - Genetic Anomaly Leading to Iron Deposition Disease (T56.5741/3)

• Process: Genetic anomaly leading to an iron deposition disease
• Patient: Post-mortem specimen of a man who died with haemochromatosis (iron deposition disease).

Observations:

• The slice of liver is diffusely darkened with a homogenous cut surface. The liver may or may not be enlarged.

Causes of Diffuse and Focal Dark Discolouration:

• Melanin pigment, carbon pigment, tattoo ink, iron, haemorrhage/bleeding (including bleeding into necrotic tissue or tumour), gangrene (necrotic skin tissue).