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ECG Practice Pathophysiology - Complete Explanation

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The Basics of ECG Reading (Foundation)

Heart Rate (HR)

• Count the R-R intervals. A quick rule: 300 ÷ (number of large squares between two R peaks).
• Normal: 60-100 bpm. Below 60 = bradycardia. Above 100 = tachycardia.

Rhythm

• Normal Sinus Rhythm (NSR): Every QRS must be preceded by a P wave. P wave is upright in lead II. Regular intervals.
• Sinus Tachycardia: NSR but HR > 100 bpm.
• Sinus Bradycardia: NSR but HR < 60 bpm.

Axis (Direction the heart's electrical impulse travels)

• Look at leads I and aVF:
  • Both positive → Normal axis (0° to +90°)
  • Lead I positive, aVF negative → Left axis deviation (LAD)
  • Lead I negative, aVF positive → Right axis deviation (RAD)
• Normal: Lead I positive (+) and aVF positive (+)

Blocks (Conduction delays)

• Right Bundle Branch Block (RBBB): Wide QRS (≥0.12s), RSR' pattern ("rabbit ears") in V1-V2. Think "WiLLiaM MaRRoW" - in RBBB, Wide complex with M shape in V1, W shape in V5.
• Left Bundle Branch Block (LBBB): Wide QRS, broad notched R wave (RR') in V5-V6. No septal Q waves.
• AV blocks are graded 1°, 2°, 3° based on PR interval prolongation or dropped beats.

Hypertrophy

• Left Ventricular Hypertrophy (LVH): Tall R wave in V5 or V6 ≥ 26 mm, or R in V5/V6 + S in V1 > 35 mm. Also: S in V1 + R in V5 > 35 mm.
• Right Ventricular Hypertrophy (RVH): Tall R wave in V1, right axis deviation.
• Left Atrial Hypertrophy (LAH): Broad, notched P wave in lead II ("mitral P"), biphasic P wave in V1 with prominent negative terminal component.

Myocardial Infarction (MI) - ST Changes

• ST Elevation = acute injury/STEMI in the territory of that lead group:
  • Leads I, aVL, V5-V6 → Lateral wall (LCx territory)
  • Leads II, III, aVF → Inferior wall (RCA territory)
  • Leads V1-V4 → Anterior wall (LAD territory)
  • V1-V2 only → Septal (proximal LAD/septal branches)
  • V1-V4 → Anteroseptal
• ST Depression in opposite leads = reciprocal change (confirms STEMI)
• Prominent T waves or ST depression alone can indicate ischemia without full infarction

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Strip-by-Strip Explanations

Strip 1

• HR: (not clear)
• Rhythm: Normal Sinus Rhythm
• Axis: Normal
• Blocks: No conduction blocks visible in any lead
• Hypertrophy: Groove sign in V1 = 10 mm; R in V4 = 26 mm; P in 4 mm; S = 55 mm
• MI: No ST elevation or depression

• The deep S wave in V1 (10 mm) + tall R in V4/V5 (26-55 mm) crosses the Sokolow-Lyon threshold (>35 mm), indicating Left Ventricular Hypertrophy (LVH).
• LVH happens because the left ventricle has been under pressure (e.g., hypertension, aortic stenosis) and its muscle mass increases. More muscle = bigger electrical signal = taller/deeper waves.
• No ischemia present on this strip.

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Strip 2

• HR: ~50 bpm (bradycardia)
• Rhythm: Normal Sinus Rhythm - identical R waves, each preceded by a P wave
• Axis: Normal (Lead I and aVF positive)
• Blocks: No AV conduction blocks observed
• Hypertrophy: None observed
• MI: ST elevation in leads I, II, aVF; ST depression in aVL → Inferior and/or lateral wall MI

• ST elevation in II, III, aVF = Inferior STEMI - the Right Coronary Artery (RCA) is blocked.
• ST depression in aVL = reciprocal change confirming inferior STEMI (mirrors the opposite wall).
• Reciprocal changes are important - they rule out benign causes of ST elevation (like early repolarization).
• Bottom line: Acute inferior MI - the RCA is occluded and the inferior wall is dying.

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Strip 3

• HR: ~100 bpm
• Rhythm: Normal Sinus Rhythm
• Axis: Normal
• Blocks: None
• Hypertrophy: None
• MI: ST elevation observed in V2 leads → MI in complete anterior version (anteroseptal)
• Also notes: aVR is positive or biphasic; T waves in DI

• ST elevation in V1-V4 = Anterior/Anteroseptal STEMI - the Left Anterior Descending (LAD) artery is blocked.
• The LAD supplies the front wall of the heart (the largest portion of the left ventricle). LAD occlusion is sometimes called the "widow maker" because it causes massive heart damage.
• Biphasic T waves in aVR can indicate left main or proximal LAD involvement.

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Strip 4

• HR: ~150 bpm
• Rhythm: Sinus Tachycardia (identical R waves, each preceded by a P wave)
• Axis: Left Axis Deviation (Lead I positive, aVF negative)
• Blocks: Left Bundle Branch Block (LBBB) - double R (RSR') pattern in V5-V6 leads
• Hypertrophy: None
• MI: ST elevation in V1-V4 → Anteroseptal MI - ST depression in aVL also observed

• LBBB occurs when the left bundle branch (the electrical wire that activates the left ventricle) is blocked. The impulse must go the "long way around," widening the QRS complex and creating a characteristic double-hump (RSR') in left-sided leads.
• Important: LBBB itself can mimic ST changes - new LBBB in a patient with chest pain is treated as a STEMI equivalent (Sgarbossa criteria apply).
• Left axis deviation + LBBB often occur together because LBBB disrupts normal conduction routing.

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Strip 5

• Axis/Rhythm: Normal Sinus Rhythm
• Blocks: No blocks to be observed
• Hypertrophy: Right Ventricular Hypertrophy can be observed (Tall R waves in V1, right axis deviation)
• MI: No MI - coronary Q waves absent; prominent ST waves; ST elevation or depression with prominent T waves in II, III, aVF

• RVH produces a tall R in V1 (normally V1 has a small R) because the enlarged right ventricle dominates.
• Causes of RVH: chronic lung disease (cor pulmonale), pulmonary hypertension, pulmonary stenosis, left-to-right shunts.
• Prominent T waves in inferior leads without frank ST elevation can indicate early ischemia or demand ischemia.

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Strip 6

• HR: 75 bpm
• Axis/Rhythm: Normal Sinus Rhythm, Normal Axis
• Blocks: No AV conduction blocks present
• Hypertrophy: Left Atrial Hypertrophy - biphasic P wave in V1; broad notched P wave in lead II (the "mitral P wave")
• MI: Persistent ST elevation / prominent T waves; ST depression / prominent inverted waves can be seen

• Left Atrial Hypertrophy (LAH) = the left atrium is enlarged and stressed.
  • Causes: mitral stenosis, mitral regurgitation, LVH, heart failure.
  • The P wave in V1 is biphasic because the atrium is enlarged - the terminal negative component in V1 is diagnostic.
  • Lead II shows a broad, bifid (double-humped) P wave > 0.12 s = "P mitrale."
• Persistent ST elevation (weeks after an event) can indicate a left ventricular aneurysm - the infarcted tissue scars into an outpouching that never repolarizes normally.

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Strip 7 (Partially filled / Practice Template)

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Strip 8

• Blocks: No blocks can be seen
• Hypertrophy: No hypertrophy can be observed
• MI: ST elevation in leads I, II, aVF (inferior + lateral); ST depression in V1, V5 (reciprocal or posterior involvement); Inferior MI

• ST elevation in I, II, aVF = Infero-lateral MI, involving RCA (inferior) and possibly LCx (lateral branch).
• ST depression in V1-V2 in the context of inferior MI can indicate posterior wall MI - a mirror image. A "posterior MI" has no leads directly overlying it, so you see its mirror: ST depression in V1-V3.

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Summary Table

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Quick Coronary Artery Memory Aid

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Clinical Cases - Full Answers

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CASE 1 - Pneumonia with Acute Inflammation

Q1. Interpret the WBC findings. What is the possible cause? What does "left shift" mean?

• A normal WBC count is 4,500 - 11,000 cells/µL.
• This patient has elevated WBC with marked neutrophilia = leukocytosis with neutrophilia, meaning the count is above normal and the dominant cell type raised is the neutrophil.
• Neutrophils are the body's first responders to bacterial infection. When bacteria invade, the immune system sends out a massive neutrophil army to fight them.

• Normally, the bone marrow releases only mature segmented neutrophils into the blood.
• During a severe bacterial infection, the demand is so high that the bone marrow releases immature neutrophils called "band cells" (they look like a horseshoe/U-shape rather than the multi-lobed mature form).
• Historically, the immature cells were on the left side of the blood smear differential count chart - hence "shift to the left."
• A left shift tells you: the infection is serious enough that the body is rushing out unfinished soldiers from the bone marrow.
• Per Robbins Pathology: "The leukocytosis occurs initially because of accelerated release of cells from the bone marrow postmitotic reserve pool... and is therefore associated with increased numbers of immature neutrophils in the blood ('band' cells), referred to as a shift to the left."

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Q2. Significance of elevated CRP and ESR in acute setting vs. chronic states

• CRP = fast responder - rises and falls quickly, ideal for tracking acute infections and judging antibiotic response.
• ESR = slow responder - rises slowly and stays elevated, better for monitoring chronic inflammatory diseases (lupus, rheumatoid arthritis, myeloma, TB).

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Q3. Normal values

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CASE 2 - Crush Syndrome / Rhabdomyolysis

Q1. Name this type of injury

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Q2. Interpret the vital signs

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Q3. Why is the urine dark brown?

1. When muscle is crushed, muscle cells (myocytes) are destroyed.
2. The cells burst open and release a protein called myoglobin - the oxygen-carrying molecule of muscle (similar to hemoglobin in blood).
3. Massive amounts of myoglobin enter the bloodstream (myoglobinemia).
4. The kidneys filter myoglobin into the urine (myoglobinuria).
5. Myoglobin is a large, dark-colored protein - it turns urine dark brown, tea-colored, or cola-colored.

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Q4. Cause of hyperkalemia and why it's life-threatening

• Inside every muscle cell, potassium (K⁺) is in high concentration.
• Crush injury destroys millions of muscle cells simultaneously.
• All that intracellular K⁺ is released at once into the bloodstream.
• Damaged kidneys cannot excrete it fast enough.
• Result: dangerously high serum potassium (hyperkalemia).

• Potassium controls the electrical membrane potential of all cells, especially the heart.
• High potassium depolarizes cardiac muscle cells, causing:
  • Peaked T waves → widened QRS → sine wave pattern → ventricular fibrillation → cardiac arrest
• Even a serum K⁺ > 6.5 mEq/L is a medical emergency requiring immediate treatment (calcium gluconate, insulin + glucose, sodium bicarbonate, dialysis).

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Q5. Why does AKI develop? Role of myoglobin

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Q6. Most common causes of death

1. Cardiac arrhythmia from hyperkalemia (most immediate threat - ventricular fibrillation)
2. Acute kidney injury / renal failure - oliguria, fluid overload, uremia
3. Metabolic acidosis with cardiovascular collapse
4. Compartment syndrome complications - nerve/vascular damage, limb loss
5. Sepsis - from secondary infection of necrotic tissue

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CASE 3 - Hypertension

Q1. Define normal BP and classify this patient

• Both readings fall in the Grade 1 range.
• When systolic and diastolic fall in different grades, use the higher grade.

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Q2. Why multiple measurements? What causes inaccurate readings?

• A single elevated reading could reflect "white coat hypertension" - anxiety-driven elevation in the clinic that doesn't represent true resting BP.
• BP fluctuates with activity, stress, caffeine, recent exercise, full bladder, position.
• Guidelines require at least 2-3 readings, on 2 separate visits to confirm a diagnosis of hypertension.
• Averaging multiple readings gives a more reliable picture of the patient's true baseline.

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Q3. How to read BP - Systolic, Diastolic, and Korotkoff Sounds

1. Place a blood pressure cuff (sphygmomanometer) around the upper arm, over the brachial artery.
2. Inflate the cuff above the expected systolic pressure (typically 160-180 mmHg) until the pulse is cut off.
3. Place a stethoscope over the brachial artery at the antecubital fossa.
4. Slowly deflate the cuff (at ~2 mmHg/second) while listening.

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CASE 4 - Iron Deficiency Anemia

Q1. Interpret RBC indices. What type of anemia?

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Q2. Likely cause and pathophysiology

1. Each menstrual cycle, the patient loses more blood (and therefore iron) than her diet can replace.
2. Iron stores (ferritin in the liver, spleen, bone marrow) are gradually depleted - this is the pre-latent stage (no symptoms yet).
3. Once stores run out, serum iron drops (latent stage) - transferrin (the transport protein) rises (it "searches" for iron).
4. When iron falls too low, the bone marrow cannot make hemoglobin properly.
5. Hemoglobin is made of heme + globin. Heme requires iron. Without iron, less heme is made.
6. The developing red cells divide more times to try to compensate, resulting in small (microcytic) cells.
7. With less heme, cells have less red pigment = hypochromic (pale) cells.
8. The patient develops: fatigue (less oxygen delivery), pallor (pale skin/mucous membranes), shortness of breath on exertion, and headaches.

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Q3. Why does iron deficiency lead to microcytic, hypochromic cells?

• Normal RBC production: The precursor cell (erythroblast) in the bone marrow divides a certain number of times, then stops and matures into a final RBC.
• The signal to stop dividing is: "enough hemoglobin has been made."
• In iron deficiency, hemoglobin synthesis is impaired, so the cell doesn't get the "stop" signal.
• The cell keeps dividing - producing more cells, each smaller than normal = microcytosis.
• Hypochromia: Each cell has less hemoglobin content because there was insufficient iron to make heme. Under the microscope, the cell looks pale with a large central pallor (the pale area normally takes up <1/3 of the cell diameter, but in IDA it expands).
• Increased RDW: Because iron deficiency develops gradually, the blood contains a mix of old normal-sized cells and new small cells, creating size variation = increased RDW. This is an early sensitive marker of IDA.

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CASE 5 - COPD

Q1. Most likely diagnosis and GOLD classification

• No significant reversibility with bronchodilator (rules out asthma)
• Heavy long-term smoking history
• Chronic productive cough (chronic bronchitis component)
• FEV₁/FVC = 0.55 post-bronchodilator - this is the defining criterion (< 0.70 confirms obstruction)

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Q2. Three risk factors in this patient

1. Heavy smoking - 45 pack-years (most important risk factor; smoking causes 85-90% of COPD cases)
2. Age 67 (COPD is progressive; cumulative damage over decades)
3. Occupational exposure - retired construction worker (chronic inhalation of dust, silica, cement particles causes airway inflammation)

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Q3. Why does this patient have a barrel-shaped chest?

1. Emphysema (from 45 years of smoking) destroys the walls between alveoli (the tiny air sacs).
2. Destroyed alveoli merge into large, floppy air spaces that cannot empty properly.
3. Air becomes trapped in the lungs - the lungs are chronically over-inflated (hyperinflation).
4. As the lungs expand chronically, they push the rib cage outward and the diaphragm downward.
5. The chest becomes rounded, with increased anterior-posterior (AP) diameter.
6. Normal AP:lateral ratio ≈ 1:2. In COPD it approaches 1:1 - the chest looks like a barrel from the side.

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Q4. Why is the FEV₁/FVC ratio important?

• FVC (Forced Vital Capacity): The total amount of air you can forcefully blow out from full lungs. Reflects lung size.
• FEV₁ (Forced Expiratory Volume in 1 second): How much air you can blow out in the first second. Reflects airway speed/flow.
• FEV₁/FVC ratio: What percentage of total lung capacity is expelled in the first second.

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Quick Reference Summary

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• LibreOffice conversion also failed due to the file size/complexity.
• Only 1 partial slide was extracted before the process timed out.

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• What it is
• Why it happens (mechanism)
• Key cells/mediators involved
• Clinical examples
• Diagrams in text form

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1. Paste the text of the questions directly here
2. Screenshot/photo the slides and send the image
3. Tell me the topic (e.g., "chronic inflammation," "granuloma," "tissue repair") and the specific questions

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Complete Answers - All Questions

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Question 1: What are the local manifestations of acute inflammation?

"The external manifestations of inflammation, often called its cardinal signs, are heat (calor), redness (rubor), swelling (tumor), pain (dolor), and loss of function (functio laesa). The first four were described over 2,000 years ago by the Roman encyclopedist Celsus; the fifth was added by Rudolf Virchow, the 'father of modern pathology.'" — Robbins & Kumar Basic Pathology

• It turns red (rubor) and feels warm (calor) - blood rushing in
• It swells (tumor) - fluid leaking out of vessels
• It hurts (dolor) - nerves being irritated by chemicals
• You can't walk on it properly (functio laesa)

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Question 2: What are the differences between acute and chronic inflammation?

• Acute = Neutrophils (think: "N for New/acute")
• Chronic = Macrophages + Lymphocytes (think: "M for Mature/long-lasting")

"In contrast to acute inflammation, which is manifested by vascular changes, edema, and predominantly neutrophilic infiltration, chronic inflammation is characterized by: infiltration by mononuclear cells (macrophages, lymphocytes, plasma cells), tissue destruction, and attempts at healing by fibrosis." — Robbins & Kumar Basic Pathology

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Question 3: Normal levels of CRP (C-Reactive Protein)

• Rises within 4-6 hours of an acute stimulus
• Can rise up to 1,000-fold in severe bacterial infection
• Falls rapidly (half-life ~19 hours) when the stimulus is removed - good for monitoring treatment response
• Highly sensitive and specific for bacterial over viral infections

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Question 4: Normal ESR (Erythrocyte Sedimentation Rate)

• Inflammatory proteins like fibrinogen coat RBCs and make them clump together (form "rouleaux" stacks like coins)
• Clumped RBCs are heavier → they sink faster → higher ESR

• CRP = fast, sensitive, short-lived → best for acute infection monitoring
• ESR = slow to rise, slow to fall → best for monitoring chronic conditions (TB, lupus, myeloma, temporal arteritis)

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Question 5: How to distinguish bacterial vs. viral infection from a blood count?

• Bacteria → Neutrophils go UP (B and N - Bacteria = Neutrophils)
• Viruses → Lymphocytes go UP (V and L - Viruses = Lymphocytes)

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Case Presentation Analysis (Pages 13-15)

The Patient:

• Sore throat for several days
• White spots on right tonsil (tonsillar exudate)
• Two inflamed lymph nodes below the jaw (anterior cervical lymphadenopathy)
• Extensive membrane covering the right tonsil
• Temperature 38.9°C (fever)
• HR 70 bpm, BP 122/74 mmHg, RR 15/min (otherwise stable)

Lab Results (Page 13):

• RBC → Normal
• WBC → Elevated (↑)
• Platelets → Normal
• Elevated neutrophil count + decreased lymphocyte count
• CRP → Markedly elevated (↑↑)
• ESR → Elevated (↑↑)

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Q: What laboratory tests would you perform?

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Q: What cause do you suspect?

• CBC shows neutrophilia (elevated neutrophils, decreased lymphocytes) = bacterial pattern
• CRP markedly elevated (bacterial infections cause very high CRP)
• Tonsillar exudate + membrane + fever + lymphadenopathy = classic bacterial presentation
• If it were viral (e.g., common cold), you would expect lymphocytosis, lower CRP, and absence of tonsillar membrane

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Complete Explanation - All Slides

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SLIDE 1 (Page 1) - Case: Crush Injury

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Q1: What type of injury do you suspect?

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Q2: What is the pathophysiological mechanism behind the signs?

1. Muscle compression → blood vessels inside the muscle are squeezed shut → muscle cells get no oxygen → cells die.
2. Dead muscle cells burst open → release intracellular fluid, myoglobin, potassium, and inflammatory mediators into the bloodstream.
3. Massive fluid shifts: fluid leaks from blood vessels into the crushed, swollen muscle tissue ("third-spacing") → blood volume drops.
4. Low blood volume → low blood pressure → heart compensates by beating faster → tachycardia (130 bpm).
5. Cold hands: With falling blood pressure, the body redirects blood to vital organs (brain, heart, kidneys) by constricting peripheral vessels → hands and feet become cold and pale = peripheral vasoconstriction.
6. Weak pulse: Reduced stroke volume from low blood volume = weak, thready pulse.

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Q3: What complications may occur?

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SLIDE 6 (Page 6) - Questions on Mechanical Injuries

Q1: List the types of mechanical injuries

• Abrasion (scratch) - superficial scraping of skin surface
• Contusion (bruise/hematoma) - blunt force without breaking skin; blood leaks into tissue
• Wound (laceration/incision) - break in skin continuity
• Fracture - break in bone
• Dislocation - displacement of joint surfaces
• Sprain - overstretching of ligaments
• Strain - overstretching of muscles/tendons
• Crush injury - severe compression of tissues

• Shock - systemic circulatory failure
• Crush syndrome - systemic effects of prolonged muscle compression
• Blast syndrome - injury from explosion pressure wave

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Q2: What are local mechanical injuries?

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Q3: What are general mechanical injuries?

• Crush syndrome: prolonged compression of large muscle mass → systemic shock, AKI, hyperkalemia
• Blast syndrome: explosion causes overpressure wave that damages air-containing organs (lungs, ears, bowel) and can cause brain injury
• Traumatic shock: massive blood or fluid loss causes cardiovascular collapse affecting all organs

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Q4: Main difference between a contusion and a wound?

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Q5: Most common cause of crush syndrome?

• Natural disasters: earthquakes (most common worldwide - buildings collapsing on victims)
• Industrial/construction accidents: machinery, falling debris
• Road traffic accidents: vehicle entrapment
• Prolonged immobilization: unconscious person lying on a limb for hours (e.g., after stroke, overdose)
• Warfare and terrorist attacks

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Q6: Pathophysiology of crush syndrome

1. Prolonged compression of muscle → ischemia (no blood flow) + direct cell membrane damage
2. Reperfusion injury when compression is released - oxygen suddenly returns and generates toxic free radicals
3. Muscle cells (myocytes) rupture → release:
   • Myoglobin → enters blood → filtered by kidneys → toxic to tubules → AKI
   • Potassium (K⁺) → hyperkalemia → cardiac arrhythmia
   • Phosphate, uric acid, creatine kinase (CK) → elevated in blood (diagnostic markers)
4. Massive third-spacing of fluid into swollen muscles → hypovolemia → shock
5. Metabolic acidosis → worsens hyperkalemia → lethal cycle

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Q7: Most common cause of death in crush syndrome?

1. Hyperkalemia → ventricular fibrillation / cardiac arrest (most immediate)
2. Acute kidney failure (leading cause of death if patient survives initial phase)
3. Metabolic acidosis with cardiovascular collapse
4. Sepsis from secondary infection

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Q8: Types of blast syndrome

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SLIDE 5 (Page 5) - Questions on Burns, Frostbite, and Electrical Injuries

Burns classification based on skin thickness:

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Frostbite classification (same principle, cold damage instead of heat):

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Types of electrical injuries:

1. True electrical injury - current passes through the body (entry + exit wound)
2. Electrical flash (arc burn) - current arcs through the air and causes intense heat burn to the skin surface, but does NOT pass through the body (no internal injury)
3. Flame injury - clothes/surroundings catch fire from the electrical arc
4. Lightning injury - extremely high voltage DC, instantaneous

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Difference between true electrical injury vs. electrical flash:

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Most common causes of death in electrical shock:

1. Ventricular fibrillation - AC current disrupts heart rhythm (most common with low/household voltage)
2. Asystole (cardiac arrest) - more common with lightning (DC current)
3. Respiratory arrest - tetanic contraction of respiratory muscles, or direct CNS injury
4. Rhabdomyolysis → AKI (especially high voltage)
5. Severe burns leading to fluid loss and sepsis

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SLIDES 3 & 4 (Pages 3-4) - MCQs on Electrical Injury

MCQ (Page 3): Typical consequence of low-voltage electrical injury?

• Low voltage (< 1000V, e.g., household current) typically causes tetanic muscle contractions and superficial burns.
• It can cause ventricular fibrillation but this is less common than with high voltage.
• Severe necrosis, unconsciousness, and long-term neurological damage are more typical of high-voltage injuries.

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MCQ (Page 4): Severity of burns/tissue damage in electrical injury primarily depends on:

• Voltage - higher voltage = more energy = deeper tissue destruction
• Duration - longer contact time = more heat deposited = more damage
• Type of current (AC vs DC) - AC is more dangerous at low voltages (causes tetanic muscle grip), DC tends to cause a single muscle contraction (throwing victim away from source)

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SLIDE 2 (Page 2) - Questions on Radiation

List the types of radiation:

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Sources of radiation:

• Natural sources: cosmic rays, radon gas, naturally occurring radioactive materials in soil/rock, natural K-40 in the body
• Medical sources: X-rays, CT scans, nuclear medicine (PET/SPECT), radiotherapy
• Industrial sources: nuclear power plants, industrial X-ray equipment
• Military sources: nuclear weapons, dirty bombs

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What is Acute Radiation Syndrome (ARS)?

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Phases of ARS:

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Which tissues are most sensitive to radiation?

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IMAGE SLIDES (Pages 7-10)

Page 7 - CONTUSION / BRUISE / HEMATOMA

• Blood leaks from damaged vessels into surrounding tissue
• Color changes over time: red → purple/blue → green → yellow as hemoglobin breaks down

• Blunt force trauma (punch, fall, hitting a hard object)
• Sports injuries
• Motor vehicle accidents
• Pathological: blood clotting disorders (hemophilia, thrombocytopenia, anticoagulant drugs like warfarin)

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Page 8 - SECOND-DEGREE BURNS

• Hot water/steam scalds
• Flame/fire contact
• Chemical burns (strong acids or alkalis)
• Sunburn (severe prolonged UV exposure)
• Hot oil, grease, food

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Page 9 - BITE WOUND

• Human bites (often fight injuries - highest infection risk due to oral bacteria)
• Animal bites: dog (most common), cat (high infection risk due to deep puncture), snake (venom risk)
• Special risk: Pasteurella multocida (cat/dog bites), Eikenella corrodens (human bites), rabies (from certain animal bites)

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Page 10 - ABRASION / SCRATCH

• Fall on rough surface (road rash, playground fall)
• Dragging injury (motor vehicle accident - body dragged on asphalt)
• Contact sports
• Friction from ropes, fabrics

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Complete Answers with Explanations

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CASE (Pages 1-5): 19-year-old male with sore throat

What lab tests would you perform?

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Lab Results (Page 3) - Interpretation:

• RBC normal - no anemia, no blood loss
• WBC elevated (↑) - infection/inflammation present
• PLT normal - no bleeding disorder or platelet consumption
• Elevated neutrophil count + decreased lymphocyte count = bacterial pattern
• CRP markedly elevated (↑↑) - strong inflammatory response, consistent with bacterial infection
• ESR elevated (↑↑) - supporting systemic inflammation

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What cause do you suspect?

• Neutrophilia (↑) + lymphopenia (↓) = classic bacterial CBC pattern
• Viral infections cause lymphocytosis and lower CRP
• Exudate membrane over tonsil + high fever + lymphadenopathy = bacterial hallmarks
• Score 4 on Centor = high strep probability

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Page 6: Five Written Questions

Q1: What are the local manifestations of acute inflammation?

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Q2: Differences between acute and chronic inflammation

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Q3: Normal CRP levels

• CRP is made by the liver in response to IL-6
• Rises within 4-6 hours, peaks at 48-72 hours
• Falls quickly when stimulus is removed → good for monitoring treatment

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Q4: Normal ESR values

• ESR rises because inflammatory proteins (fibrinogen) coat RBCs → they clump and sink faster
• Slower to rise and fall than CRP → better for monitoring chronic disease (TB, lupus, myeloma)

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Q5: Bacterial vs. viral infection on blood count

• Bacteria → Neutrophils (B + N)
• Viruses → Lymphocytes (V + L)

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Page 7 & 15: Exudate vs. Transudate

• Causes: infection, cancer, inflammation (pleurisy, pericarditis, peritonitis)
• Clinical example: pus in a lung abscess, cloudy fluid in bacterial pleuritis

• High hydrostatic pressure (e.g., heart failure → fluid pushed out of vessels)
• Low oncotic pressure (e.g., hypoalbuminemia from liver disease/malnutrition → less "suction" keeping fluid inside vessels)
• Causes: heart failure, liver cirrhosis, nephrotic syndrome, hypoproteinemia
• Clinical example: clear fluid in cardiac failure pleural effusion

"An exudate is an extravascular fluid that has a high protein concentration and contains cellular debris. Its presence implies an increase in the permeability of small blood vessels, typically during an inflammatory reaction. A transudate is a fluid with low protein content... produced as a result of osmotic or hydrostatic imbalance across the vessel wall without an increase in vascular permeability." — Robbins & Kumar Basic Pathology

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MCQ Answers (Pages 8-14)

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Page 8: Which is a cardinal sign of inflammation?

• a) Ulceration
• b) Cyanosis
• c) Erythema ✅
• d) Numbness

• Erythema = redness - this IS one of the 5 cardinal signs (rubor). It occurs because vasodilation brings more blood to the inflamed area.
• Ulceration is a result of tissue necrosis, not a cardinal sign
• Cyanosis = blue discoloration from lack of oxygen - opposite of inflammation's redness
• Numbness = loss of sensation, not a feature of inflammation (inflammation causes PAIN, not numbness)

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Page 9: Which cell type is involved in the EARLY phase of inflammation?

• a) Macrophages
• b) Keratinocytes
• c) Plasma cells
• d) Fibroblasts
• e) Neutrophils ✅

• Neutrophils are the first cells to arrive at a site of acute inflammation - they appear within 30 minutes to a few hours of injury.
• They are the "first responders" of the immune system - like police at a crime scene.
• They arrive first because: (1) they are the most abundant WBC in blood, (2) they are highly responsive to chemical signals (chemokines) released by injured tissue.
• Macrophages arrive later (days) and dominate chronic inflammation.
• Plasma cells = antibody-producing cells, involved in adaptive immunity (chronic/late phase)
• Fibroblasts = repair cells that make collagen, involved in healing (late phase)
• Keratinocytes = skin cells, not inflammatory cells

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Page 10: Which is responsible for SWELLING in inflammation?

• a) Increased vascular permeability ✅
• b) Increased sensitivity of peripheral nerve endings
• c) Immobilization
• d) Vasoconstriction
• e) Increased blood flow

1. Inflammation triggers mediators: histamine, bradykinin, leukotrienes (especially LTC4, LTD4)
2. These mediators cause endothelial cells of capillaries to contract and pull apart, creating gaps between them
3. Plasma proteins (albumin, fibrinogen) that normally STAY inside vessels now leak out through these gaps
4. These proteins accumulate in the interstitial tissue
5. The proteins pull water out of the vessels by osmosis → fluid accumulates in tissue = edema = swelling

• Option b (nerve sensitivity) causes pain, not swelling
• Option d (vasoconstriction) would REDUCE blood flow - the opposite happens in inflammation (vasodilation)
• Option e (increased blood flow) causes redness and heat, not the swelling itself - it is the PERMEABILITY that causes the fluid shift

"Increased vascular permeability allows leakage of fluid from blood vessels into the damaged tissue, resulting in swelling (edema)." — Goodman & Gilman's Pharmacological Basis of Therapeutics

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Page 11: Which is an important FUNCTION of inflammation?

• a) Formation of immunological memory
• b) Removal of apoptotic cell bodies
• c) Deactivation of reactive oxygen species
• d) Defense against infections ✅
• e) Degradation of senescent cells

1. Destroy and remove the injurious agent (bacteria, viruses, toxins, foreign bodies)
2. Wall off the damaged area to prevent spread
3. Initiate repair of the damaged tissue

• Option a (immunological memory) = function of the adaptive immune system (B and T lymphocytes), not of inflammation itself
• Option b (removal of apoptotic cells) = function of macrophages through efferocytosis, a homeostatic process distinct from inflammation
• Option c (deactivation of reactive oxygen species) = function of antioxidants - inflammation actually PRODUCES ROS as a weapon against bacteria
• Option e (senescent cell degradation) = function of the immune system broadly, not inflammation specifically

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Page 12: Which is TRUE about neutrophils?

• a) They release potent proteases that have high specificity for damaged cells or pathogens
• b) They typically have rounded or kidney-shaped nuclei and little cytoplasm
• c) They are recruited to the site of injury quickly and are short-lived cells ✅
• d) They play an important role in healing and fibrosis
• e) They stay alive for a long period of time after they leave the circulation

• a) WRONG - Neutrophil proteases (elastase, collagenase, MMP) have LOW specificity - they damage both pathogens AND healthy surrounding tissue. This is actually why inflammation can be destructive.
• b) WRONG - Neutrophils have multi-lobed (segmented) nuclei - usually 3-5 lobes connected by thin strands. Rounded or kidney-shaped nuclei describe monocytes (kidney-shaped) or lymphocytes (large round nucleus).
• c) CORRECT - Neutrophils:
  • Arrive at injury within 30 min - 2 hours (fastest of all immune cells)
  • Survive only 1-2 days in tissues (very short-lived)
  • They "die at the battlefield" - they phagocytose bacteria, release their granule contents, then die and become pus
• d) WRONG - Healing and fibrosis are driven by macrophages and fibroblasts. Neutrophils are destroyers, not builders.
• e) WRONG - The opposite is true. Neutrophils have a lifespan of only 6-8 hours in blood and 1-2 days in tissue - one of the shortest-lived cells in the body.

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Page 13: Predominant cell type in CHRONIC inflammation?

• a) Neutrophils
• b) Eosinophils
• c) Basophils
• d) Helmet cells
• e) Macrophages ✅

1. Macrophages - the most important cell, dominant in chronic inflammation
2. Lymphocytes (T and B cells)
3. Plasma cells (antibody-secreting B cells)

• They are long-lived (weeks to months, unlike neutrophils which last 1-2 days)
• They secrete cytokines (IL-1, TNF, IL-6) that perpetuate the inflammatory response
• They present antigens to T cells, linking innate to adaptive immunity
• They attempt tissue repair but also cause tissue destruction through proteases and ROS
• In granulomatous inflammation, they transform into epithelioid cells and giant cells
• Neutrophils = acute inflammation only
• Eosinophils = parasitic infections and allergic reactions
• Basophils = allergic reactions (similar role to mast cells)
• "Helmet cells" (schistocytes) = fragmented RBCs seen in haemolytic anaemia - NOT inflammatory cells

"Chronic inflammation is characterized by infiltration by mononuclear cells, which include macrophages, lymphocytes, and plasma cells." — Robbins & Kumar Basic Pathology

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Page 14: Which is a HALLMARK of ACUTE inflammation?

• a) Infiltration of lymphocytes and plasma cells into the tissue site
• b) Formation of scar tissue
• c) Onset of days-weeks after the injury
• d) Increased vascular permeability ✅
• e) Vasoconstriction

• a) WRONG - Lymphocytes and plasma cells are hallmarks of CHRONIC inflammation. In acute inflammation, neutrophils are the dominant infiltrating cells.
• b) WRONG - Scar tissue (fibrosis) is a feature of chronic inflammation and the repair phase. Acute inflammation does not form scars - it resolves.
• c) WRONG - Acute inflammation begins within minutes to hours after injury. Days-to-weeks onset is the timeline for chronic inflammation.
• d) CORRECT - The two hallmarks of acute inflammation are:
  1. Vascular changes - vasodilation + increased vascular permeability (causes edema/exudate)
  2. Neutrophil infiltration - rapid recruitment of neutrophils to the site
• e) WRONG - Vasoconstriction is the very first, brief (seconds) response to injury (neurogenic reflex). After that, vasodilation takes over and persists throughout acute inflammation. Vasoconstriction is NOT a hallmark of inflammation.

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Summary Table - All MCQ Answers

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Complete Answers with Explanations - 2.pdf (19 Slides)

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SLIDES 1-4: Picture-Based Injury Identification

Slide 1 - ABRASION / SCRATCH

• Falling on a rough surface (road rash, playground)
• Being dragged on asphalt (traffic accidents)
• Friction from ropes, cables, fabrics
• Contact sports (rugby, wrestling)
• Industrial accidents with moving machinery

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Slide 2 - BITE WOUND

• Human bites (highest infection risk - oral flora includes Eikenella corrodens, streptococci, anaerobes)
• Dog bites (most common animal bite - Pasteurella multocida, Capnocytophaga)
• Cat bites (deep punctures - very high infection rate due to needle-like teeth)
• Snake bites (venom injection risk + tissue necrosis)
• Insect bites (local reaction or disease transmission - malaria, Lyme disease)

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Slide 3 - SECOND-DEGREE BURNS

• Hot water or steam scalds
• Flame/fire contact (brief)
• Prolonged sun exposure (severe sunburn)
• Hot oil, grease, soup
• Chemical burns (acids, alkalis)

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Slide 4 - CONTUSION / BRUISE / HEMATOMA

• Blunt trauma (punch, fall, collision with hard object)
• Sports injuries (direct blows)
• Road traffic accidents
• Pathological: coagulation disorders (hemophilia), thrombocytopenia, anticoagulant medications (warfarin, heparin)

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SLIDE 5: Mechanical Injuries - 8 Questions

Q1: List the types of mechanical injuries

• Abrasion/scratch, Contusion/bruise, Wound/laceration, Fracture, Dislocation, Sprain, Strain, Crush injury

• Crush syndrome, Blast syndrome, Traumatic shock

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Q2: What are local mechanical injuries?

Q3: What are general mechanical injuries?

• Crush syndrome - compressed muscle → systemic AKI, hyperkalemia, shock
• Blast syndrome - explosion pressure wave → multi-organ injury
• Traumatic shock - massive blood/fluid loss → cardiovascular collapse

Q4: Main difference between contusion and wound?

Q5: Most common cause of crush syndrome?

• Earthquakes (buildings collapsing) - most common worldwide
• Industrial/construction accidents (machinery entrapment)
• Motor vehicle accidents (prolonged entrapment)
• Prolonged immobilization (unconscious patient lying on a limb - seen in strokes, drug overdose)

Q6: Pathophysiology of crush syndrome

1. Prolonged compression of large muscle groups → ischemia (no blood/oxygen to muscle cells)
2. Muscle cell death (rhabdomyolysis) - cell membranes rupture, releasing contents:
   • Myoglobin → enters bloodstream → filtered by kidneys → directly toxic to renal tubules → tubular necrosis → Acute Kidney Injury (AKI)
   • Potassium (K⁺) → floods out of dead cells → hyperkalemia → cardiac arrhythmia
   • Phosphate, uric acid, CK → elevated in blood (diagnostic markers)
3. Massive fluid shift (third-spacing) - fluid leaks into swollen, dead muscle tissue → blood volume drops → hypovolemic shock (low BP, tachycardia, cold peripheries)
4. Reperfusion injury when compression released - oxygen returns → generates free radicals → worsens cell damage
5. Metabolic acidosis - anaerobic metabolism in ischemic tissue produces lactic acid
6. Acidosis worsens hyperkalemia → vicious cycle → cardiac arrest

Q7: Most common cause of death in crush syndrome?

1. Hyperkalemia → ventricular fibrillation/cardiac arrest (most immediate - can kill within minutes of release)
2. Acute kidney injury (leading cause of death in those who survive initial phase)
3. Metabolic acidosis with cardiovascular collapse
4. Sepsis from secondary infection of necrotic muscle

Q8: Types of blast syndrome

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SLIDE 6: Burns, Frostbite & Electrical Injuries

Burns classification by skin thickness:

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Frostbite classification (same principle, cold instead of heat):

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Types of electrical injuries:

1. True electrical injury - current passes through body (entry wound + exit wound visible)
2. Electrical flash (arc burn) - current arcs through air near the body, causing intense heat burns to skin surface only. Current does NOT pass through the body. No internal injury.
3. Flame injury - clothes or environment catch fire from the electrical arc
4. Lightning injury - extremely high voltage DC, instantaneous, massive energy

Difference between true electrical injury vs. electrical flash:

Most common causes of death in electrical shock:

1. Ventricular fibrillation (most common with AC current / household voltage)
2. Asystole (more common with lightning DC current)
3. Respiratory arrest - tetanic spasm of respiratory muscles or direct CNS damage
4. Severe burns → fluid loss, infection, sepsis (high-voltage injuries)
5. Rhabdomyolysis → Acute Kidney Injury (especially high-voltage)

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SLIDES 7-8: Electrical Injury MCQs

Slide 7: Severity of electrical burns depends on:

• Voltage - higher voltage = more energy driven through tissue = deeper burns
• Duration - longer contact = more heat deposited = more tissue death; also more dangerous because muscle tetany from AC current can "freeze" the victim onto the source
• Type of current (AC vs DC):
  • AC (alternating current - household power): more dangerous at low voltages because it causes tetanic muscle contraction - the victim cannot let go
  • DC (direct current - batteries, lightning): usually causes a single contraction that throws the victim away from the source

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Slide 8: Typical consequence of LOW-VOLTAGE electrical injury?

• a) Cardiac arrest - can occur but is less typical of low voltage; more common with high voltage
• b) Severe tissue necrosis - characteristic of high-voltage (>1000V) injuries which cause massive deep burns and rhabdomyolysis
• c) Minor burns or muscle contractions ✅ - low voltage (<1000V, e.g., 120-240V household current) typically causes: superficial burns at contact points, tetanic muscle contractions, tingling/paresthesias, and transient neuropathy
• d) Unconsciousness and long-term neurological damage - more typical of high-voltage injuries with prolonged current flow

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SLIDE 9: Radiation Questions

Types of radiation:

Sources of radiation:

• Natural: cosmic rays (from outer space), radon gas (from ground), radioactive minerals in rocks/soil, K-40 in the human body itself
• Medical: X-rays, CT scans, PET/SPECT nuclear medicine, radiotherapy for cancer
• Industrial: nuclear power plants, industrial X-ray inspection, food irradiation
• Military: nuclear weapons, dirty bombs (radiological dispersal devices)

What is Acute Radiation Syndrome (ARS)?

Phases of ARS:

Which tissues are most sensitive to radiation?

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SLIDE 10: Crush Syndrome Case (22-year-old construction worker)

• Trapped 8 hours in ventilation shaft - body compressed against walls
• Weak pulse + HR 130 bpm + cold hands = Hypovolemic shock
• Type of injury: Crush syndrome
• Mechanism: prolonged compression → muscle ischemia → rhabdomyolysis → fluid third-spacing → shock → peripheral vasoconstriction (cold hands)
• Complications: AKI, hyperkalemia, cardiac arrest, metabolic acidosis, compartment syndrome

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SLIDES 11-14: Microcirculation & Capillary MCQs

Slide 11: Which is NOT a characteristic of capillaries?

• A) Thin endothelial lining for easy exchange
• B) Absence of smooth muscle in the walls
• C) Larger diameter compared to arterioles ✅
• D) Presence of fenestrations (pores) in some capillaries

• Capillaries are the smallest blood vessels - their diameter (5-10 µm) is actually just large enough for a single red blood cell to squeeze through
• Arterioles are larger (10-100 µm diameter) and contain smooth muscle in their walls
• Options A, B, D are all TRUE about capillaries:
  • A - TRUE: Capillary walls are just one cell thick (single layer of endothelium) - this thinness allows easy exchange of O₂, CO₂, nutrients, and waste
  • B - TRUE: Capillaries have NO smooth muscle - they cannot constrict/dilate on their own
  • D - TRUE: Fenestrated capillaries (with pores/windows) exist in organs that need rapid exchange: kidneys (glomeruli), intestines, endocrine glands

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Slide 12 & 13: Primary factor driving fluid OUT of capillary into interstitial space?

• A) Plasma oncotic pressure
• B) Hydrostatic pressure within the capillary ✅
• C) Interstitial fluid hydrostatic pressure
• D) Concentration of albumin in the interstitial fluid

• Option A (plasma oncotic pressure) is the force that pulls fluid BACK IN to the capillary (because albumin in blood creates osmotic suction)
• Option C (interstitial hydrostatic pressure) resists filtration (pushes back), it does NOT drive fluid out
• Option D (albumin in interstitium) is part of interstitial oncotic pressure - it would pull fluid OUT of capillary, but this is the minor force, not the primary one

"The Starling equation states that fluid movement across a capillary wall is determined by the net pressure across the wall, which is the sum of hydrostatic and oncotic pressures... Capillary hydrostatic pressure is a force favoring filtration out of the capillary." — Costanzo Physiology

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Slide 14: Microvascular changes during inflammatory response?

• A) Decreased permeability → reduced fluid leakage
• B) Vasodilation of arterioles + increased permeability of capillaries ✅
• C) Constriction of postcapillary venules
• D) Reduced blood flow to capillary beds

1. Vasodilation of arterioles (mediated by histamine, prostaglandins) → increases blood flow to the area → causes redness (rubor) and heat (calor)
2. Increased vascular permeability of capillaries and postcapillary venules (mediated by histamine, bradykinin, leukotrienes) → gaps form between endothelial cells → protein-rich fluid leaks out → swelling/edema (tumor)

• A is the opposite - inflammation INCREASES permeability
• C is wrong - postcapillary venules actually become more permeable and dilate; they do not constrict
• D is wrong - inflammation INCREASES blood flow (vasodilation), not reduces it

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SLIDE 15: Shock Questions

Types of shock by cause:

Types of shock by clinical severity:

Causes of hypovolemic shock:

• Hemorrhagic: trauma, GI bleeding (ulcer, varices), ruptured ectopic pregnancy, aortic aneurysm rupture
• Non-hemorrhagic fluid loss: severe vomiting, diarrhea, burns (plasma loss), excessive sweating, diabetes (polyuria), third-spacing (pancreatitis, bowel obstruction)

What is distributive shock?

• Cardiac output may actually be HIGH (heart pumps harder to compensate)
• But blood pressure is LOW because SVR (systemic vascular resistance) is very low
• Types: Septic shock (most common), anaphylactic shock, neurogenic shock (spinal cord injury), adrenal insufficiency

Hypovolemic vs. Distributive shock:

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SLIDE 16: Acid-Base Case - Young Woman

• Na⁺ 135 mmol/L (normal 135-145) → Normal
• K⁺ 5.0 mmol/L (normal 3.5-5.0) → Normal
• Blood pH 7.53 (normal 7.35-7.45) → ALKALOSIS (pH > 7.45)
• pCO₂ 22 mmHg (normal 35-45) → LOW (CO₂ is being blown off)
• Bicarbonate 24 mmol/L (normal 22-26) → Normal

1. pH 7.53 = alkalosis (too high, too basic)
2. pCO₂ 22 = very low. CO₂ is an acid. Low CO₂ = less acid in blood = alkalosis
3. HCO₃⁻ 24 = normal. If the kidneys had caused this, bicarbonate would be elevated. Since bicarbonate is normal and CO₂ is low, this is a respiratory problem.
4. Conclusion: Primary Respiratory Alkalosis

• H₂O + CO₂ ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻
• Less CO₂ → reaction shifts left → less H⁺ → pH rises → alkalosis

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SLIDE 17: Electrolyte Case - 70-year-old woman

• Na⁺ 142 mmol/L (normal 135-145) → Normal
• K⁺ 2.1 mmol/L (normal 3.5-5.0) → Very LOW = Hypokalemia
• Cl⁻ 94 mmol/L (normal 98-106) → Slightly low
• CO₂ (bicarbonate) 30 mmol/L (normal 22-26) → HIGH = Metabolic Alkalosis

• Vomit contains HCl → loss of acid → blood becomes alkalotic (metabolic alkalosis)
• Diarrhea/vomiting loses K⁺ directly → hypokalemia
• Kidneys try to retain Na⁺ (low volume) → exchange K⁺ and H⁺ for Na⁺ → worsen the hypokalemia and alkalosis

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SLIDE 18: Match Acid-Base Disorders to Causes

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SLIDE 19: Match Acid-Base Disorders to Compensatory Mechanisms

• "Opposite system compensates" - respiratory problem → kidney compensates; metabolic problem → lung compensates
• Acidosis → body tries to reduce acid or add base
• Alkalosis → body tries to add acid or remove base

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Complete Answers with Explanations - 3.pdf (17 Pages)

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PATIENT 1 (Pages 1-4): Allergic Rhinitis - 25-year-old female

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Q1: What type of hypersensitivity is present?

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Q2: Explain the mechanism of development

1. Allergen (e.g., pollen) enters the body through mucous membranes
2. Antigen-presenting cells (dendritic cells) capture and present the allergen to naïve T helper cells
3. In genetically predisposed individuals, T cells differentiate into Th2 cells (not the normal Th1 path)
4. Th2 cells release IL-4 and IL-13 → these cytokines stimulate B cells to class-switch and produce IgE antibodies specific to the allergen
5. IgE antibodies circulate and bind to high-affinity IgE receptors (FcεRI) on the surface of mast cells (in tissue) and basophils (in blood)
6. The person is now sensitized - they feel nothing yet, but are armed and ready

1. The allergen binds to and cross-links two adjacent IgE molecules on the mast cell surface
2. This cross-linking triggers mast cell degranulation - the cell bursts open and releases stored mediators
3. Immediate reaction (within minutes):
   • Histamine, prostaglandins, leukotrienes are released → vasodilation, increased permeability, smooth muscle contraction → sneezing, runny nose, itchy eyes
4. Late phase reaction (4-8 hours later):
   • New mediators are synthesized: leukotrienes, cytokines (IL-4, IL-5), chemokines
   • These recruit eosinophils, more mast cells, basophils → sustained inflammation → nasal congestion and chronic symptoms

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Q3: What mediators are involved and what are their functions?

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Q4: Key cells in maintaining chronic inflammation in allergic rhinitis

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PRACTICE TASK 2 (Page 5): Prick Test

How to perform the prick test:

1. The patient must stop antihistamines for at least 72 hours before the test (they block the reaction)
2. The forearm (inner surface) is cleaned with alcohol and marked
3. A small drop of each allergen extract is placed on the skin at marked positions (plus positive control = histamine, negative control = saline)
4. A lancet or needle is used to prick through each drop at a 45° angle, making a tiny hole in the epidermis (not drawing blood)
5. After 15-20 minutes, the skin is observed for reactions

When is the test positive?

• Positive: A wheal (raised bump) ≥ 3 mm larger than the negative control forms at the allergen site. There is usually also surrounding redness (flare). This indicates the patient is sensitized to that allergen.
• Negative: No wheal forms (same as saline control). The patient is not sensitized to that allergen.
• Invalid: If the positive control (histamine) doesn't produce a wheal → the patient may have taken antihistamines, or skin is unresponsive → test must be repeated.

What type of hypersensitivity is tested?

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PRACTICE TASK 3 (Page 6): Tuberculin Test (Mantoux Test)

What is the tuberculin test?

How to perform:

1. 0.1 mL of PPD (Purified Protein Derivative) - an extract of TB antigens - is injected intradermally into the volar (inner) surface of the forearm
2. This creates a small raised bleb (bubble) at the injection site
3. The patient returns in 48-72 hours (NOT 15 minutes like the prick test - this is important!)
4. The induration (hardened, raised area) is measured with a ruler in millimeters (not the redness/erythema)

Reading (positive threshold varies by risk group):

• ≥ 5 mm = positive in HIV+ patients, immunocompromised, close TB contacts
• ≥ 10 mm = positive in healthcare workers, immigrants from high-prevalence countries
• ≥ 15 mm = positive in low-risk individuals

Mechanism of skin changes - Type IV hypersensitivity:

1. PPD antigens are presented to memory T lymphocytes (CD4+ T cells) that were sensitized by prior TB exposure
2. These T cells recognize the antigens and become activated → release cytokines (IFN-γ, TNF, IL-2)
3. Cytokines recruit macrophages and more T cells to the injection site
4. This accumulation of cells causes the characteristic induration (hardening) - it is NOT edema, it is cellular infiltration
5. This takes 48-72 hours because T cells need time to travel to the site and multiply - hence "delayed type" hypersensitivity (Type IV = delayed)

• Prick test = Type I (minutes, IgE + mast cells, wheal)
• Tuberculin = Type IV (48-72 hours, T cells + macrophages, induration)

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CASE 1 (Pages 7-11): R.F., 23-year-old female - Renal Case

• Serum Creatinine: 2.6 mg/dL (normal 0.6-1.5) → Elevated
• BUN: 24.0 mg/dL (normal 7-21) → Elevated
• pH: 7.32 (normal 7.35-7.45) → Acidosis
• (Urinalysis and renal function tests shown on pages 9-10 - likely showing hematuria, proteinuria, low GFR)

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Q1: Primary diagnosis based on creatinine and BUN?

• Creatinine 2.6 mg/dL (nearly double the upper limit) and BUN 24 mg/dL (elevated) = Azotemia - waste products are building up in the blood because the kidneys cannot filter them properly
• When azotemia causes symptoms (nausea, vomiting, fatigue) it is called uremia
• The combination of: hematuria (red-brown urine) + oliguria (minimal urine) + elevated creatinine + puffy feeling (edema) + acidosis = classic Nephritic Syndrome, most likely from glomerulonephritis

"AKI may present with reduced or no urine output (oliguria or anuria), hypertension, and other signs of renal dysfunction. Laboratory tests reveal an increase in BUN and serum creatinine - collectively termed azotemia." — Robbins & Kumar Basic Pathology

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Q2: Why does R.F. have a low hematocrit?

1. Failing renal tubular cells produce less EPO
2. Bone marrow receives less EPO signal → produces fewer RBCs
3. Fewer RBCs = lower hematocrit = normocytic normochromic anemia

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Q3: How does R.F.'s condition lead to blood in the urine (hematuria)?

1. Normal glomerular capillary walls act as a selective filter - they have pores small enough to block blood cells (which are ~7-8 µm) from entering the filtrate
2. In glomerulonephritis, immune-mediated inflammation damages the glomerular basement membrane (GBM) and disrupts the filtration barrier
3. The damaged membrane now has enlarged gaps → red blood cells and proteins can pass through into the filtrate (Bowman's capsule)
4. These RBCs travel down the nephron tubules → appear in the urine = hematuria
5. The dark red-brown color of the urine = blood + myoglobin mixed with urine (concentrated)
6. On microscopy: red cell casts (RBCs trapped in protein casts) are pathognomonic of glomerular bleeding

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Q4: What do the renal function tests indicate? How do they relate to urine output?

• Elevated creatinine (2.6) + BUN (24) = kidneys are NOT filtering waste products effectively = reduced GFR (Glomerular Filtration Rate)
• GFR represents how much blood the kidneys filter per minute. Normal = ~100-120 mL/min.
• When GFR falls → less filtrate is formed → oliguria (minimal urine output, as R.F. reports)
• The retained wastes (creatinine, urea, uric acid, potassium) accumulate in blood → cause nausea, vomiting, fatigue, altered mental state (uremic symptoms)
• pH 7.32 = metabolic acidosis - damaged kidneys cannot excrete enough H⁺ (acid) → acid accumulates in blood

• Normal ratio BUN:Creatinine = ~10:1 to 20:1
• Here BUN 24 / Creatinine 2.6 = ~9:1 → suggests intrinsic renal disease (glomerulonephritis) rather than pre-renal cause

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Q5: What caused the puffy feeling (edema)?

1. Reduced GFR → less sodium (Na⁺) and water are filtered and excreted → Na⁺ and water retained in the body → builds up in interstitial spaces → generalized edema (puffy face, limbs)
2. Activation of the renin-angiotensin-aldosterone system (RAAS) → kidneys detect reduced perfusion → release renin → generates angiotensin II → stimulates aldosterone → kidneys retain even more Na⁺ and water → worsens edema

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Page 12: Hemostasis Questions

What are the phases of hemostasis?

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Tests for each phase:

• Platelet count - is there enough platelets?
• Bleeding time (BT) - time until bleeding stops from a small skin cut
• Platelet function analyzer (PFA-100) - tests platelet adhesion and aggregation

• PT (Prothrombin Time) - tests the extrinsic pathway (factors VII, X, V, II, fibrinogen)
• aPTT (activated Partial Thromboplastin Time) - tests the intrinsic pathway (factors XII, XI, IX, VIII, X, V, II, fibrinogen)
• Thrombin Time (TT) - tests fibrinogen conversion to fibrin
• Fibrinogen level

• D-dimer - elevated when fibrin has been broken down (suggests clot formation and lysis, e.g., in DVT, PE, DIC)
• Fibrinogen degradation products (FDPs)

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How to perform the Lee-White test:

1. Draw 3 mL of venous blood into a plain glass tube (no anticoagulant)
2. Note the exact time of collection
3. Tilt the tube every 30 seconds at 37°C
4. Record the time when the blood no longer flows (it has clotted)
5. Normal: 5-15 minutes

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What does aPTT test?

• Normal aPTT: 25-35 seconds
• Prolonged aPTT means one of these intrinsic factors is deficient or inhibited
• Clinical uses: monitoring heparin therapy, detecting hemophilia A (factor VIII deficiency) or hemophilia B (factor IX deficiency), lupus anticoagulant

"The PTT assay assesses the function of the proteins in the intrinsic pathway (factors XII, XI, X, IX, VIII, V, II, and fibrinogen)." — Robbins & Kumar Basic Pathology

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What does PT test?

• Normal PT: 11-15 seconds
• Prolonged PT = deficiency of extrinsic pathway factors (especially factor VII)
• Clinical uses: monitoring warfarin (Coumadin) therapy, assessing liver function (liver makes most clotting factors), detecting vitamin K deficiency

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What is INR?

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Pages 13-16: Iron Deficiency Anemia Case - 56-year-old female

• ESR 20 mm/h (borderline), CRP 3 mg/L (normal)
• Hb 90 g/L (normal women > 120 g/L) → Severely low
• RBC 3.6 × 10¹²/L (low end)
• Hct 0.29 (normal 0.36-0.47) → Low
• MCHC 31 g/dL (normal 32-36) → Low (hypochromic)
• RDW↑ (increased size variability)
• Serum Fe/s ↓, TIBC ↑, Ferritin ↓ → classic iron deficiency pattern

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Q: What can you tell based on the patient's history?

1. Slow, hidden GI blood loss (e.g., peptic ulcer, colorectal cancer, polyp) → gradual iron depletion
2. Body compensates for months → when Hb drops below ~80-90 g/L → symptomatic anemia
3. Patient presents with fatigue, palpitations, dyspnea on exertion, cognitive symptoms

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Q: Main complaints to worry about?

• Upper GI bleeding (above the ligament of Treitz) - blood is digested by stomach acid → turns black/tarry
• Source could be: peptic ulcer (most common), gastric cancer, esophageal varices, duodenal ulcer
• Must be urgently investigated with upper endoscopy (gastroscopy)
• At age 56 + black stool + anemia → must rule out GI malignancy

• HR 120 + systolic murmur = tachycardia with hyperdynamic circulation from severe anemia (heart compensates by beating faster to maintain oxygen delivery)
• Hb 90 g/L = severe anemia requiring treatment

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Q: Why does this patient have dark/black stool?

1. Bleeding occurs somewhere in the upper gastrointestinal tract (stomach, duodenum, proximal small bowel)
2. Blood (red, containing hemoglobin) enters the intestinal lumen
3. Hemoglobin is digested by gastric acid and intestinal bacteria → converted to hematin (a black compound)
4. This black material mixes with stool → produces melena - characteristically black, tarry, sticky, foul-smelling stools

• Hematochezia (bright red blood in stool) = lower GI bleeding (colorectal)
• Melena (black stool) = upper GI bleeding (>250 mL blood loss usually needed to produce melena)

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Q: What's with her vital signs?

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Q: What's pathological in laboratory findings?

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Q: What other diagnostic procedures would you propose?

1. Upper GI endoscopy (gastroscopy) - urgent, to identify the source of GI bleeding (ulcer? cancer? varices?)
2. Colonoscopy - to rule out colorectal cancer or polyps
3. Fecal occult blood test (FOBT) - if endoscopy not immediately available
4. Stool H. pylori antigen test - Helicobacter pylori is the most common cause of peptic ulcer
5. Reticulocyte count - assess bone marrow's response to iron deficiency
6. MCV (Mean Corpuscular Volume) - will be low (microcytic) confirming IDA
7. Peripheral blood smear - will show microcytic, hypochromic RBCs; pencil cells (elongated cells)
8. Renal function (creatinine, BUN) - to rule out renal contribution to anemia
9. If malignancy suspected: CT abdomen/pelvis, tumor markers (CEA, CA 19-9)

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Page 17: Endocrine Disorders - 10 Questions

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Q1: What is negative feedback in endocrine regulation?

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Q2: Example using the HPA (Hypothalamic-Pituitary-Adrenal) axis

Hypothalamus releases CRH (Corticotropin-Releasing Hormone)
           ↓
Pituitary releases ACTH (Adrenocorticotropic Hormone)
           ↓
Adrenal cortex releases CORTISOL
           ↓
Cortisol feeds back → INHIBITS both Hypothalamus and Pituitary
           ↑_______________________________________________|
                        NEGATIVE FEEDBACK

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Q3: Main causes of hyperthyroidism

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Q4: What is Hashimoto's thyroiditis?

1. Loss of immune tolerance to thyroid antigens (thyroglobulin, thyroid peroxidase)
2. Autoantibodies produced: anti-TPO (anti-thyroid peroxidase) and anti-thyroglobulin
3. CD8+ cytotoxic T cells infiltrate and destroy thyroid follicles
4. Macrophages and lymphocytes replace normal thyroid tissue
5. Goiter may form early (compensatory thyroid enlargement), then thyroid shrinks as it's destroyed
6. Progressive thyroid destruction → hypothyroidism

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Q5: Lab findings in hypo vs. hyperthyroidism

• In hypothyroidism: less T4 → less negative feedback → pituitary releases more TSH (elevated)
• In hyperthyroidism: too much T4 → strong negative feedback → pituitary suppresses TSH (very low)

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Q6: Role of TSH in thyroid regulation

1. Stimulate uptake of iodine into the thyroid gland
2. Increase synthesis of thyroglobulin, T3, and T4
3. Stimulate release of stored thyroid hormones into circulation
4. Promote growth of thyroid follicular cells (thyroid hypertrophy and hyperplasia)

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Q7: How are cortisol and aldosterone regulated?

• HPA axis: Hypothalamus → CRH → Pituitary → ACTH → Adrenal cortex (zona fasciculata) → Cortisol
• Negative feedback: Cortisol inhibits CRH and ACTH
• Circadian rhythm: Peaks in early morning (6-8 AM), lowest at midnight
• Stress response: Stress → CRH surge → ACTH → cortisol → mobilizes glucose, suppresses immune system

• RAAS system (main): Low blood pressure / low Na⁺ / high K⁺ → kidneys release Renin → converts Angiotensinogen to Angiotensin I → ACE converts to Angiotensin II → stimulates adrenal cortex (zona glomerulosa) → releases Aldosterone → kidneys retain Na⁺ and water, excrete K⁺
• Also regulated by: hyperkalemia (directly stimulates aldosterone release), ACTH (minor role)

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Q8: Causes of Cushing syndrome

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Q9: What happens in Addison's disease?

• No cortisol → fatigue, weakness, weight loss, hypoglycemia, inability to respond to stress
• No aldosterone → kidneys cannot retain Na⁺ → Na⁺ lost in urine (hyponatremia), K⁺ retained (hyperkalemia) → hypotension, salt craving
• No negative feedback on pituitary → ACTH rises dramatically → ACTH binds to melanocyte receptors → hyperpigmentation (bronze skin, especially skin folds, scars, gums) - this is the distinctive feature of Addison's

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Q10: Difference between primary and secondary adrenal insufficiency