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Respiratory (Sinus) Arrhythmia - Effect of Inspiration on Heart Rate

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What happens across the full respiratory cycle?

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Mechanism

1. During inspiration, lung inflation activates pulmonary stretch receptors, which inhibit the cardioinhibitory center in the medulla. This causes a withdrawal of vagal tone to the sinoatrial (SA) node - with less parasympathetic braking, the SA node fires faster, increasing heart rate.
2. During expiration, vagal tone is restored, slowing the SA node back down.

"With inspiration, a withdrawal of vagal tone increases heart rate; by comparison, expiration is associated with a drop in heart rate."

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Key Points

• Sinus arrhythmia is normal and adaptive - not pathological
• It is most prominent in young, healthy individuals and diminishes with age
• Reduced or absent respiratory sinus arrhythmia can indicate autonomic neuropathy (e.g., in diabetes)
• Clinically, the deep breathing test (6 breaths/min) is used to quantify vagal function - a heart rate variation of less than 10-15 bpm suggests vagal dysfunction
• The irregularity seen on ECG reflects changing R-R intervals in sync with the respiratory cycle
• Medical Physiology (Boron & Boulpaep), p. 730
• Goldman-Cecil Medicine, Chapter 51

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SHORT NOTES FOR MBBS 1st YEAR EXAM

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1. HORMONES

Definition

Classification by Chemical Nature

Mechanism of Action

• Cannot cross cell membrane
• Bind to surface receptors
• Act via second messengers:
  • cAMP (Gs protein - activates adenylyl cyclase)
  • cGMP
  • IP3 + DAG (Gq protein)
  • Ca²+ / Calmodulin

• Cross the cell membrane freely
• Bind to intracellular receptors (cytoplasm or nucleus)
• Hormone-receptor complex binds DNA → alters gene transcription → new protein synthesis

Properties of Hormones

• Secreted in small amounts
• Act at low concentrations
• Have specific target cells/receptors
• May have permissive, synergistic, or antagonistic effects
• Controlled by negative feedback

Feedback Control

• Negative feedback - most common; hormone inhibits its own secretion (e.g., cortisol inhibits ACTH/CRH)
• Positive feedback - rare (e.g., estrogen surge triggering LH surge at ovulation)

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2. MUTATION

Definition

Classification by Structural Change

• Shifts the reading frame
• All downstream codons changed
• Usually severe effect

• Deletion - loss of a chromosomal segment
• Insertion - addition of extra DNA
• Inversion - segment reversed
• Translocation - segment moved to another chromosome

Classification by Effect on Protein Function

• Loss of function - reduced/absent activity (most common; usually recessive)
• Gain of function - novel/increased activity (usually dominant; e.g., oncogenes)
• Dominant negative - mutant protein inhibits normal protein

Causes of Mutation (Mutagens)

• Physical - ionizing radiation (X-rays, gamma rays), UV light
• Chemical - base analogs, alkylating agents, intercalating agents (acridine dyes)
• Biological - viruses (e.g., HPV, EBV)
• Spontaneous - errors during DNA replication

Mutation vs Polymorphism

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3. CANCER

Definition

Key Terminology

• Neoplasm - new abnormal growth
• Benign - localized, encapsulated, well-differentiated, does NOT metastasize
• Malignant (Cancer) - invasive, poorly differentiated, metastasizes
• Carcinoma - cancer of epithelial origin
• Sarcoma - cancer of mesenchymal origin (bone, muscle, connective tissue)
• Leukemia/Lymphoma - cancer of blood/lymphoid cells

Carcinogenesis (Multistep Process)

• Irreversible DNA mutation caused by a carcinogen
• Cell is "initiated" but not yet transformed

• Initiated cell undergoes clonal expansion
• Promoters are not mutagens (e.g., hormones, bile acids)
• Reversible stage

• Further mutations accumulate
• Cells acquire full malignant phenotype - invasion + metastasis

Molecular Basis of Cancer

• Oncogenes: RAS, MYC, HER2
• Tumor suppressors: p53 (most common mutation in cancers), Rb (retinoblastoma), APC (colorectal cancer)

Characteristics of Cancer Cells (Hallmarks)

1. Self-sufficiency in growth signals
2. Insensitivity to anti-growth signals
3. Evading apoptosis
4. Limitless replicative potential (telomerase activation)
5. Sustained angiogenesis (VEGF)
6. Tissue invasion and metastasis

Carcinogens

• Chemical - tobacco smoke (lung), aflatoxin (liver), asbestos (mesothelioma)
• Physical - UV radiation (skin cancer), ionizing radiation (leukemia, thyroid)
• Biological/Viral - HPV (cervical), HBV/HCV (liver), EBV (Burkitt lymphoma), H. pylori (gastric)
• Hormonal - estrogen (breast, endometrial cancer)

Benign vs Malignant

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• Hormones: "PSA" - Peptide (surface receptor/cAMP), Steroid (intracellular receptor/gene transcription), Amino acid derivatives
• Mutations: "MNS-FID" - Missense, Nonsense, Silent, Frameshift, Insertion, Deletion
• Cancer genes: "Oncogenes = accelerator" | "Tumor suppressors = brakes"

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AGMCH - Department of Physiology: All Clinical Problem Answers

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PROBLEM 1 - Calculate MCV (Hematocrit = 45%, RBC = 5 million/mm³)

MCV (fl) = [Hematocrit (%) / RBC count (millions/mm³)] × 10

MCV = (45 / 5) × 10 = 90 fl

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Questions:

• MCV (Mean Corpuscular Volume) - size of RBC
• MCH (Mean Corpuscular Hemoglobin) - Hb content per RBC
• MCHC (Mean Corpuscular Hemoglobin Concentration) - Hb concentration per unit volume of RBC
• Colour Index (CI) - older index, now rarely used

• It is independent of RBC count and Hematocrit errors
• It has a very narrow normal range (32-38%)
• Cannot exceed 38% (physiological limit - saturation of Hb in RBC)

• Classifies anemia by cell size (normocytic, microcytic, macrocytic)
• Helps diagnose iron deficiency (low MCV), B12/folate deficiency (high MCV)

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PROBLEM 2 - Calculate MCH (Hb = 14 g/dL, RBC = 5 million/mm³)

MCH (pg) = [Hb (g/dL) / RBC count (millions/mm³)] × 10

MCH = (14 / 5) × 10 = 28 pg

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Questions:

• Indicates the average weight of Hb per RBC
• Low MCH = hypochromic anemia (iron deficiency)
• High MCH = macrocytic anemia (B12/folate deficiency)
• Less useful alone than MCHC because it doesn't account for cell size

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PROBLEM 3 - Calculate MCHC (Hb = 15 g/dL, PCV = 45%)

MCHC (%) = [Hb (g/dL) / PCV (%)] × 100

MCHC = (15 / 45) × 100 = 33.3%

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Questions:

• Hemoglobin inside the RBC can only be dissolved up to a maximum concentration of ~38 g/dL
• Beyond this concentration, Hb would crystallize or precipitate
• This is the physiological solubility limit of hemoglobin in the RBC cytoplasm
• Therefore, MCHC >38% (hyperchromia) is considered not physiologically possible and indicates a lab error (e.g., lipemia, spherocytosis)

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PROBLEM 4 - Calculate Colour Index (Hb = 16 g/dL, RBC = 6 million/mm³; Normal Hb = 15 g/dL, Normal RBC = 5 million/mm³)

CI = (Patient Hb% / Normal Hb%) ÷ (Patient RBC% / Normal RBC%) Patient Hb% = (16/15) × 100 = 106.7% Patient RBC% = (6/5) × 100 = 120%

CI = (106.7 / 120) = 0.89

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Questions:

• CI = 1 → normochromic
• CI < 0.85 → hypochromic
• CI > 1.15 → hyperchromic (e.g., macrocytic anemia)

• CI does not give an absolute value of Hb per RBC
• It depends on RBC count which can have up to 10% error
• It does not distinguish between microcytic hypochromic and macrocytic hyperchromic anemias accurately
• MCH and MCHC are more accurate and have replaced CI in clinical practice

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PROBLEM 5 - Calculate Physiological Dead Space (TV = 450 ml, Alveolar PCO₂ = 40 mmHg, Expired PCO₂ = 26 mmHg)

VD/VT = (PaCO₂ - PECO₂) / PaCO₂

VD/VT = (40 - 26) / 40 = 14/40 = 0.35

VD = 0.35 × 450 = 157.5 ml ≈ 158 ml

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Questions:

• ~150 ml (approximately 2 ml/kg body weight)
• Includes nose, pharynx, larynx, trachea, bronchi, bronchioles (up to terminal bronchioles)

• Positive pressure ventilation
• Pulmonary embolism (alveolar dead space increases)
• Emphysema
• Upright posture (increases alveolar dead space at apex)
• Hypotension / low cardiac output
• Drugs: atropine (dilates airways)

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PROBLEM 6 - Calculate Stroke Volume & Cardiac Output (Fick's Principle)

CO = O₂ consumption / (Arterial O₂ - Venous O₂) CO = 245 / (19.5 - 14.8) ml/100ml CO = 245 / 4.7 × 100 ml = 245 / 0.047 CO = 5212 ml/min ≈ 5.2 L/min

SV = CO / HR = 5212 / 70 = ~74.5 ml/beat

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Questions:

• Stroke Volume (SV): Volume of blood ejected per beat. Normal = 70 ml
• Cardiac Output (CO): Volume of blood pumped per minute. CO = SV × HR. Normal = 5 L/min

• Preload (venous return/EDV) - Frank-Starling law
• Afterload (arterial resistance/BP)
• Contractility (inotropic state of heart)
• Heart Rate - direct relation

• Fick's principle (O₂ consumption method) - gold standard
• Thermodilution (clinical standard using Swan-Ganz catheter)
• Dye dilution (indicator dilution - Evans blue)
• Echocardiography (Doppler)
• Ballistocardiography

CI = CO / Body Surface Area (BSA) Normal = 2.5-4.2 L/min/m² Used to compare individuals of different body sizes.

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PROBLEM 7 - Calculate GFR (Inulin: P = 0.24 mg/ml, U = 34 mg/ml, V = 0.9 ml/min)

GFR = (U × V) / P

GFR = (34 × 0.9) / 0.24 = 30.6 / 0.24 = 127.5 ml/min

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Questions:

• Glomerular hydrostatic pressure (direct)
• Bowman's capsule pressure (inverse)
• Plasma colloid osmotic pressure (inverse)
• Filtration coefficient (Kf) - permeability × surface area
• Renal blood flow/Renal plasma flow
• Sympathetic stimulation (decreases GFR)

FF = GFR / RPF = 125 / 625 = 0.2 (20%)

• 20% of plasma reaching glomerulus is filtered
• Normal = ~20%

Clearance = (U × V) / P

• Inulin clearance = GFR (125 ml/min)
• PAH clearance = Effective Renal Plasma Flow (~625 ml/min)

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PROBLEM 8 - Calculate Absolute Eosinophil Count (TLC = 6000/mm³, Eosinophils = 15%)

AEC = TLC × (Eosinophil % / 100)

AEC = 6000 × 15/100 = 900 cells/mm³

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Questions:

• More accurate than differential count percentage
• Reflects true eosinophil count independent of total WBC
• Normal = 40-440 cells/mm³

• 500 cells/mm³ = Eosinophilia → investigate for allergies, parasites

• Allergic disorders (asthma, hay fever, urticaria)
• Parasitic infections (especially tissue-invading: Ascaris, Filaria)
• Skin diseases (eczema, pemphigus)
• Drug reactions
• Addison's disease
• Tropical eosinophilia

• Cushing's syndrome (excess cortisol)
• Typhoid fever (Widal's law)
• Acute bacterial infections
• Stress

• Kill parasites (Major Basic Protein, Eosinophil cationic protein)
• Modulate allergic reactions (inactivate histamine, degradate leukotrienes)
• Phagocytosis of antigen-antibody complexes
• Limit inflammatory response

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PROBLEM 9 - Calculate Dyspnoeic Index (Resting ventilation = 6 L/min, MVV = 100 L/min)

Dyspnoeic Index = (Resting pulmonary ventilation / MVV) × 100

DI = (6/100) × 100 = 6%

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Questions:

DI = (Resting ventilation / MVV) × 100

• Normal <30%; >75% = severe dyspnoea; >40% = dyspnoea on mild exertion

• Normal = 150-170 L/min (males); 80-120 L/min (females)
• Reflects airway patency and respiratory muscle strength

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PROBLEM 10 - Calculate RV and FRC (IRV = 3L, ERV = 1.8L, TV = 0.5L, TLC = 6L)

VC = IRV + TV + ERV = 3 + 0.5 + 1.8 = 5.3 L

RV = TLC - VC = 6 - 5.3 = 0.7 L

FRC = ERV + RV = 1.8 + 0.7 = 2.5 L

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Questions:

• Prevents complete collapse of alveoli between breaths
• Maintains continuous gas exchange during expiration
• Keeps alveoli moist
• Stabilizes alveolar gas composition preventing wide swings in O₂ and CO₂

• Nitrogen washout method (Fowler's method)
• Helium dilution method (closed circuit)
• Body plethysmography (most accurate, measures trapped gas too)
• Radiological method (chest X-ray + calculation)
• Note: RV and FRC cannot be measured by simple spirometry

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PROBLEM 11 - Calculate Net Effective Filtration Pressure

Net EFP = (Glomerular HP - Bowman's HP) - (Plasma OP - Filtrate OP) Net EFP = (60 - 15) - (30 - 0) Net EFP = 45 - 30 = +15 mmHg

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Questions:

• Form the filtration slits (slit diaphragm) - main barrier to protein passage
• Provide structural support to glomerular capillary loops
• Synthesize glomerular basement membrane components
• Regulate Kf (filtration coefficient)
• Loss of podocytes = proteinuria (as in nephrotic syndrome)

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PROBLEM 12 - Calculate Lung Compliance (ΔV = 1L, ΔP = 5 cmH₂O)

Compliance = ΔV / ΔP = 1000 ml / 5 cmH₂O = 200 ml/cmH₂O

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Questions:

C = ΔV/ΔP. Normal = 200 ml/cmH₂O (0.2 L/cmH₂O) It is the ease with which lungs can be expanded.

• Emphysema (destruction of elastic tissue)
• Old age
• Surfactant present (normal condition)
• Lungs at mid-range volume

• Static compliance: Measured at no airflow (equilibrium)
• Dynamic compliance: Measured during breathing; affected by airway resistance
• Specific compliance: Compliance corrected for lung volume (C/FRC)

• Elastic tissue: Elastin fibres reduce compliance when stretched
• Surface tension: Main determinant; reduced by surfactant (increases compliance)
• Lung volume: Low compliance at extremes of volume
• Pulmonary blood volume: Increased blood = decreased compliance
• Disease: Fibrosis, edema (decrease); Emphysema (increase)

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PROBLEM 13 - Calculate Cardiac Output by Fick's Principle

CO = O₂ consumption / A-V O₂ difference CO = 250 / (19 - 14) ml/dL CO = 250 / 5 × 100 CO = 5000 ml/min = 5 L/min

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Questions:

CO = O₂ consumed / (AO₂ - VO₂)

SV = CO / HR. Normal = 70 ml/beat. Range = 60-90 ml/beat.

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PROBLEM 14 - Calculate TmG

Filtered load = Plasma conc × GFR = (300/100 mg/ml) × 100 = 3 mg/ml × 100 = 300 mg/min

Excreted = U × V = 10 × 1 = 10 mg/min

TmG = Filtered - Excreted = 300 - 10 = 290 mg/min

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Questions:

• In DM, plasma glucose is high (e.g., 300+ mg/dL)
• Filtered load exceeds TmG → excess glucose appears in urine (glucosuria)
• Renal threshold for glucose = ~180 mg/dL (point where glucosuria starts)
• Helps assess severity and monitor treatment of DM

• Ideally, glycosuria should start sharply at one plasma glucose level (renal threshold)
• In reality, there is a gradual, rounded transition called "splay"
• Splay occurs because not all nephrons have identical transport capacities
• Some nephrons reach TmG earlier, some later → gradual rise in urine glucose

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PROBLEM 15 - Calculate Respiratory Quotient

CO₂ = 30,000 ml × 4.2/100 = 1260 ml

RQ = CO₂ produced / O₂ consumed = 1260 / 1470 = 0.857 ≈ 0.86

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Questions:

RQ = VCO₂ / VO₂

• Identify substrate being metabolized (carbohydrate, fat, protein)
• Monitor nutritional status and metabolic state
• Assess response to exercise
• RQ >1.0 = lipogenesis (excess carbohydrate intake)
• RQ <0.7 = ketosis or starvation (fat breakdown + ketone production)
• Used in calculating Basal Metabolic Rate (BMR)

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PROBLEM 16 - Calculate PAH Clearance (P = 0.02 mg/ml, U = 14 mg/ml, V = 0.9 ml/min)

Clearance = (U × V) / P = (14 × 0.9) / 0.02 = 12.6 / 0.02 = 630 ml/min

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Questions:

Clearance = (U × V) / P (in ml/min)

• Inulin clearance → measures GFR (125 ml/min)
• PAH clearance → measures ERPF (~625 ml/min)
• Creatinine clearance → estimates GFR clinically
• Urea clearance → estimates GFR (less accurate)
• Diodrast clearance → measures ERPF

• Measures Effective Renal Plasma Flow (ERPF) ~625 ml/min
• PAH is filtered AND completely secreted by proximal tubule → entire plasma reaching peritubular capillaries is cleared of PAH
• ERPF = PAH clearance
• Renal Blood Flow = ERPF / (1 - Hematocrit) = 625 / 0.55 ≈ 1125 ml/min

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PROBLEM 17 - Calculate Urea Clearance (P = 20 mg/100ml, U = 10 mg/ml, V = 1.2 ml/min)

P = 20 mg/100 ml = 0.2 mg/ml

Clearance = (U × V) / P = (10 × 1.2) / 0.2 = 12 / 0.2 = 60 ml/min

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Questions:

• Estimates GFR but LESS accurate than inulin because:
  • Urea is partially reabsorbed by tubules (40-50%)
  • Reabsorption varies with urine flow rate
• "Standard clearance" (Vm <2 ml/min): Normal = 40-65 ml/min
• "Maximum clearance" (Vm >2 ml/min): Normal = 60-75 ml/min
• Urea clearance test - a clinical test to assess renal function when inulin is unavailable

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PROBLEM 18 - Calculate Inulin Clearance (P = 35 mg/100ml, U = 25 mg/ml, V = 1.4 ml/min)

P = 35 mg/100 ml = 0.35 mg/ml

Clearance = (U × V) / P = (25 × 1.4) / 0.35 = 35 / 0.35 = 100 ml/min

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Questions:

• Freely filtered (not bound to plasma proteins)
• Neither secreted nor reabsorbed
• Non-toxic

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PROBLEM 19 - Calculate CO and SV (Arterial O₂ = 19 ml/100ml, Venous O₂ = 14 ml/100ml, O₂ consumption = 270 ml/min, HR = 70/min)

CO = 270 / (19-14) ml/100ml = 270 / 0.05 = 5400 ml/min = 5.4 L/min

SV = CO / HR = 5400 / 70 = 77 ml/beat

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Questions:

• SV: Volume ejected per beat. Normal = 70 ml
• CO: Volume per minute. CO = SV × HR. Normal = 5 L/min
• CI: CO/BSA. Normal = 2.5-4.2 L/min/m²

• Normalizes CO for body surface area → allows comparison between individuals
• More useful than CO alone in critically ill patients
• CI < 2.2 L/min/m² = cardiogenic shock
• Used to guide fluid therapy and vasopressor use in ICU

1. Fick's principle (O₂ method)
2. Indicator dilution (dye: Evans blue, Indocyanine green)
3. Thermodilution (clinical gold standard - cold saline via Swan-Ganz catheter)
4. Echocardiography (Doppler)
5. Impedance cardiography
6. Radionuclide ventriculography

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PROBLEM 20 - Calculate Total Body Water

TBW = (Amount injected - Amount excreted) / Concentration at equilibrium

TBW = (100 - 4) / 0.002 = 96 / 0.002 = 48,000 ml = 48 L

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Questions:

• Dilution principle - inject marker and measure its final concentration
• D₂O (deuterium oxide) / THO (tritiated water) → TBW
• Inulin, mannitol → ECF
• Evans blue, radioisotope albumin → Plasma volume
• ICF = TBW - ECF

• Decreased venous return → decreased CO → decreased BP
• Tachycardia (sympathetic reflex)
• Vasoconstriction (peripheral)
• Oliguria / anuria (reduced renal perfusion)
• Increased ADH secretion, increased aldosterone (RAAS)
• Thirst
• Severe: organ failure, shock, death

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PROBLEM 21 - Calculate Alveolar Ventilation (TV = 500 ml, Dead space = 150 ml, RR = 12/min)

Alveolar Ventilation = (TV - Dead space) × RR AV = (500 - 150) × 12 = 350 × 12 = 4200 ml/min = 4.2 L/min

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Questions:

V/Q = Alveolar ventilation / Pulmonary blood flow

• Overall V/Q = 4.2 / 5.0 = 0.84
• Apex of lung: V/Q > 1 (relatively over-ventilated, under-perfused) = ~3.3
• Base of lung: V/Q < 1 (relatively under-ventilated, over-perfused) = ~0.6
• Best matching at mid-lung level

• Acts as a buffer - prevents large swings in alveolar gas composition
• Warms and humidifies inspired air
• Filters particles and pathogens
• Voice production (larynx)
• Physiological dead space measurement helps assess V/Q mismatch in disease

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PROBLEM 22 - Calculate Dead Space (N₂ washout method: Area with N₂ = 70 cm², Area without N₂ = 30 cm², Volume of air = 500 ml)

Dead space = (Area without N₂ / Total area) × Tidal volume DS = (30 / 100) × 500 = 150 ml

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Questions:

• Dyspnoea: Subjective sensation of difficulty or labored breathing
• Apnoea: Cessation of breathing
• Eupnoea: Normal, quiet, effortless breathing (12-18/min)

• Tachypnoea: Increased respiratory rate (>20/min); rate increased, depth normal
• Bradypnoea: Decreased respiratory rate (<12/min)

• Sudden onset of severe breathlessness at night, waking the patient from sleep
• Usually occurs 1-2 hours after lying down
• Cause: fluid redistribution from dependent parts to lungs in supine position → pulmonary edema
• Classic sign of Left Ventricular Failure (LHF)
• Relieved by sitting upright or getting up to open a window

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PROBLEM 23 - Calculate Filtration Fraction (GFR = 120 ml/min, RPF = 625 ml/min)

FF = GFR / RPF = 120 / 625 = 0.192 ≈ 0.2 (20%)

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Questions:

FF = GFR / RPF = 125/625 = 0.2 or 20% Means 20% of plasma entering glomerulus is filtered.

• Increased FF: In hypovolemia, heart failure (efferent vasoconstriction increases)
• Decreased FF: Renal artery stenosis, hypotension

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PROBLEM 24 - Calculate MCV (RBC = 4.5 million/mm³, PCV = 40%, Hb = 14 g/dL)

MCV = (PCV / RBC) × 10 = (40 / 4.5) × 10 = 88.9 fl ≈ 89 fl

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PROBLEM 25 - Calculate MCH (Hb = 14.5 g/dL, RBC = 4.8 million/mm³, PCV = 42%)

MCH = (Hb / RBC) × 10 = (14.5 / 4.8) × 10 = 30.2 pg

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PROBLEM 26 - Physiological Dead Space (same as Problem 5)

VD = [(40-26)/40] × 450 = 0.35 × 450 = 157.5 ml

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PROBLEM 27 - Breathing Reserve and Dyspnoeic Index

RPV = TV × RR = 500 × 12 = 6000 ml/min = 6 L/min

BR = MVV - RPV = 130 - 6 = 124 L/min

DI = (RPV / MVV) × 100 = (6/130) × 100 = 4.6%

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PROBLEM 28 - Calculate CO by Fick's Principle

CO = O₂ consumption / (AO₂ - VO₂) CO = 270 / (190 - 140) ml/L CO = 270 / 50 = 5.4 L/min

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PROBLEM 29 - Calculate Cardiac Index (CO = 5.20 L/min, BSA = 1.65 m²)

CI = CO / BSA = 5.20 / 1.65 = 3.15 L/min/m²

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Summary Formula Sheet:

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PHYSIOLOGY CLINICAL PROBLEMS - SIMPLE ANSWERS

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🔴 RED CELL INDICES

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MCV Calculation #1

MCV = (PCV ÷ RBC) × 10 = (45 ÷ 5) × 10 = 90 fl ✅ Normal (80–100 fl)

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MCV Calculation #2

MCV = (40 ÷ 4.5) × 10 = 89 fl ✅ Normal

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MCH Calculation #1

MCH = (Hb ÷ RBC) × 10 = (14 ÷ 5) × 10 = 28 pg ✅ Normal (27–33 pg)

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MCH Calculation #2

MCH = (14.5 ÷ 4.8) × 10 = 30.2 pg ✅ Normal

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MCHC Calculation

MCHC = (Hb ÷ PCV) × 100 = (15 ÷ 45) × 100 = 33.3% ✅ Normal (32–38%)

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Colour Index (CI)

Patient Hb% = (16/15) × 100 = 106.7% Patient RBC% = (6/5) × 100 = 120% CI = 106.7 ÷ 120 = 0.89 ✅ Normal (~1.0)

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Q&A - Red Cell Indices (applies to all above problems)

• MCV - size of RBC (fl)
• MCH - Hb content per RBC (pg)
• MCHC - Hb concentration in RBC (%)
• Colour Index (old, rarely used now)

• Classifies type of anemia (see table below)
• Guides cause (iron deficiency → low MCV; B12/folate → high MCV)

• Doesn't give absolute value
• Affected by RBC counting errors
• MCH and MCHC are more accurate replacements

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🟠 EOSINOPHIL COUNT

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Absolute Eosinophil Count

AEC = TLC × (% ÷ 100) = 6000 × 0.15 = 900/mm³ ⚠️ Normal = 40–440/mm³ → This is EOSINOPHILIA

• Neopasms
• Allergies (asthma, hay fever, urticaria)
• Addison's disease
• Collagen vascular disease / skin diseases
• Parasites (especially tissue-invading worms)

• Kill parasites (release toxic proteins)
• Control allergic reactions (break down histamine)
• Phagocytose antigen-antibody complexes

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🟡 RESPIRATORY PROBLEMS

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Dead Space #1 & #2 (Bohr's Equation)

VD = [(PA CO₂ − PE CO₂) ÷ PA CO₂] × TV VD = [(40 − 26) ÷ 40] × 450 = (14/40) × 450 = 157.5 ml

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Dead Space (Fowler's N₂ Washout Method)

DS = (Area without N₂ ÷ Total area) × TV = (30 ÷ 100) × 500 = 150 ml ✅ Normal

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Q&A - Dead Space

• Pulmonary embolism
• Emphysema
• Positive pressure ventilation
• Upright posture
• Low cardiac output

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Alveolar Ventilation

Alveolar Ventilation = (TV − DS) × RR = (500 − 150) × 12 = 4200 ml/min = 4.2 L/min

• Buffers alveolar gas composition
• Warms and humidifies air
• Filters particles

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Dyspnoeic Index #1

DI = (Resting ventilation ÷ MVV) × 100 = (6 ÷ 100) × 100 = 6% ✅ Normal (<30%)

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Dyspnoeic Index #2 (with Breathing Reserve)

Resting ventilation = 500 × 12 = 6000 ml = 6 L/min Breathing Reserve = MVV − Resting vent = 130 − 6 = 124 L/min DI = (6 ÷ 130) × 100 = 4.6% ✅ Normal

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Q&A - Dyspnoeic Index

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RV and FRC

VC = IRV + TV + ERV = 3 + 0.5 + 1.8 = 5.3 L RV = TLC − VC = 6 − 5.3 = 0.7 L FRC = ERV + RV = 1.8 + 0.7 = 2.5 L

• Prevents alveolar collapse between breaths
• Keeps gas exchange continuous
• Stabilizes O₂ and CO₂ levels

• Helium dilution method
• Nitrogen washout
• Body plethysmography (Cannot be measured by spirometry)

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Lung Compliance

Compliance = ΔV ÷ ΔP = 1000 ÷ 5 = 200 ml/cmH₂O ✅ Normal

• ↑ Compliance: emphysema, surfactant
• ↓ Compliance: fibrosis, pulmonary edema, ARDS

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Respiratory Quotient

CO₂ produced = 30,000 × 4.2% = 1260 ml RQ = CO₂ produced ÷ O₂ consumed = 1260 ÷ 1470 = 0.86

• Carbohydrate = 1.0
• Protein = 0.8
• Fat = 0.7
• Mixed diet = 0.85

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Breathing Definitions (Quick Reference)

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🟢 CARDIAC OUTPUT PROBLEMS

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CO + SV by Fick's #1

CO = O₂ consumed ÷ (A−V O₂ diff) = 245 ÷ (19.5−14.8) = 245 ÷ 4.7 × 100 = 5.2 L/min SV = CO ÷ HR = 5200 ÷ 70 = 74 ml/beat

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CO + SV by Fick's #2

CO = 270 ÷ (19−14) × 100 = 270 ÷ 0.05 = 5400 ml/min = 5.4 L/min SV = 5400 ÷ 70 = 77 ml/beat

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CO by Fick's #3

CO = 270 ÷ (190−140) = 270 ÷ 50 = 5.4 L/min

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Cardiac Index

CI = CO ÷ BSA = 5.20 ÷ 1.65 = 3.15 L/min/m² ✅ Normal (2.5–4.2)

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Q&A - Cardiac Output

• SV = blood ejected per beat. Normal = 70 ml
• CO = SV × HR. Normal = 5 L/min
• CI = CO ÷ BSA. Normal = 2.5–4.2 L/min/m²

• Preload (venous return) ↑ → CO ↑
• Afterload (resistance) ↑ → CO ↓
• Contractility ↑ → CO ↑
• Heart rate ↑ → CO ↑

1. Fick's principle
2. Dye dilution (Evans blue)
3. Thermodilution (Swan-Ganz catheter) - clinical standard
4. Echocardiography (Doppler)

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🔵 RENAL PROBLEMS

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GFR (Inulin Clearance) #1

GFR = (U × V) ÷ P = (34 × 0.9) ÷ 0.24 = 30.6 ÷ 0.24 = 127.5 ml/min ✅ Normal

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Inulin Clearance

Clearance = (25 × 1.4) ÷ 0.35 = 35 ÷ 0.35 = 100 ml/min

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Net Effective Filtration Pressure

Net EFP = (60−15) − (30−0) = 45 − 30 = +15 mmHg ✅ Filtration occurs

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Filtration Fraction

FF = GFR ÷ RPF = 120 ÷ 625 = 0.19 ≈ 20% ✅ Normal

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PAH Clearance (ERPF)

Clearance = (14 × 0.9) ÷ 0.02 = 12.6 ÷ 0.02 = 630 ml/min = Effective Renal Plasma Flow ✅

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Urea Clearance

Clearance = (10 × 1.2) ÷ 0.2 = 12 ÷ 0.2 = 60 ml/min ✅ Normal (40–65 ml/min)

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TmG (Tubular Maximum for Glucose)

Filtered load = (300/100) × 100 = 300 mg/min Excreted = 10 × 1 = 10 mg/min TmG = 300 − 10 = 290 mg/min (Normal: 320–375 mg/min)

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Q&A - Renal

• ↑ Glomerular HP → ↑ GFR
• ↑ Bowman's pressure → ↓ GFR
• ↑ Plasma oncotic pressure → ↓ GFR
• Sympathetic stimulation → ↓ GFR

• Form filtration slit diaphragm
• Main barrier against protein loss
• Loss of podocytes = proteinuria

• Inulin (gold standard)
• Creatinine (clinical use)
• Cystatin C
• Radioisotopes (⁵¹Cr-EDTA)

• Inulin → GFR
• PAH → ERPF (Renal plasma flow)
• Creatinine → estimated GFR (clinical)
• Urea → approximate GFR

• Normal renal threshold = 180 mg/dL
• In DM: plasma glucose >180 → filtered load exceeds TmG → glucose in urine
• Explains glucosuria in DM

• Threshold = plasma concentration at which substance first appears in urine (180 mg/dL for glucose)
• TmG = max rate of reabsorption (320–375 mg/min)

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🟣 TOTAL BODY WATER

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TBW Calculation

TBW = (Injected − Excreted) ÷ Concentration = (100−4) ÷ 0.002 = 96 ÷ 0.002 = 48,000 ml = 48 L

• D₂O or THO (tritiated water) dilution - measures TBW
• Inulin/mannitol - measures ECF
• Evans blue dye - measures plasma volume

• ↓ BP, ↑ heart rate
• Peripheral vasoconstriction
• Oliguria
• ↑ ADH, ↑ Aldosterone (RAAS activation)
• Thirst
• Severe → organ failure, shock

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📋 MASTER FORMULA SHEET

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AMPHIBIAN GRAPH PRACTICAL - ALL ANSWERS

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📄 PAGE 1 - Graph 1

Q1. Identify the graph?

Q2. Describe the graph?

• X-axis = Time | Y-axis = Muscle contraction (height)
• A = Point of stimulus application
• B = Latent period (delay between stimulus and contraction - ~0.01 sec)
• B to C = Contraction period (muscle shortens - ~0.04 sec)
• C to D = Relaxation period (muscle returns to rest - ~0.05 sec)
• E = Peak of contraction (maximum height)
• The wavy line at the bottom = time marker (tuning fork/signal marker)

Q3. How to get this graph?

• Take a frog, destroy brain and spinal cord (pithed frog)
• Dissect the gastrocnemius muscle with sciatic nerve attached
• Mount on kymograph
• Apply a single maximal stimulus to the nerve
• One single bell-shaped curve is obtained

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📄 PAGE 1 - Graph 2

Q1. Identify the graph?

Q2. Describe the graph?

• Shows response to a single threshold/progressive stimulus
• Smaller, lower curve compared to MS
• PS = Progressive/Sub-maximal stimulus
• At A = stimulus applied; B = start of contraction; C = peak; D = relaxation

Q3. How to get this graph?

• Same setup as above (frog gastrocnemius on kymograph)
• Apply stimulus starting from below threshold
• Gradually increase until a contraction just appears
• The first visible contraction = threshold stimulus

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📄 PAGE 2 - Graph 1 (Multiple overlapping curves, PS, black background)

Q1. Identify the graph?

Q2. Describe the graph?

• Multiple twitch curves of increasing heights shown overlapping
• PS = Progressive stimulus
• As stimulus intensity increases → more motor units recruited → bigger contraction
• Shows that whole muscle follows graded response (unlike individual muscle fibres which follow all-or-none law)

Q3. How to get this graph?

• Mount frog gastrocnemius on kymograph
• Apply stimuli of gradually increasing strength from sub-threshold to maximal
• Each successive stimulus produces a bigger curve until maximum is reached

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📄 PAGE 2 - Graph 2 (A, B, C curves with PS, PC1, PC2, PC3)

Q1. Identify the graph?

Q2. Describe the graph?

• A = single twitch (normal)
• B = second stimulus applied before full relaxation → summation (bigger than A)
• C = third stimulus applied even earlier → even bigger summation
• PC1, PC2, PC3 = Points of stimulation (progressively earlier in relaxation phase)
• Shows that if stimuli are applied before the muscle fully relaxes, contractions add up

Q3. How to get this graph?

• Apply two or more stimuli to the nerve
• Second stimulus given before the muscle fully relaxes from the first
• The contractions summate (add up) to give a bigger response

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📄 PAGE 3 - Graph 1 (A, B, C, D, E, F - 6 small twitches)

Q1. Identify the graph?

Q2. Describe the graph?

• 6 successive twitches (A, B, C, D, E, F) shown
• Each successive twitch is slightly taller than the previous one
• Shows gradual increase in contraction height with repeated equal stimuli
• After a few contractions, height stabilizes
• This is the Treppe effect (staircase phenomenon)

Q3. How to get this graph?

• Apply repeated stimuli of equal strength at regular intervals (~1/sec)
• First few contractions increase in height (staircase)
• Cause: Ca²+ accumulates inside muscle with each contraction, increasing subsequent force

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📄 PAGE 3 - Graph 2 (A, B, C panels with PS, PC marks)

Q1. Identify the graph?

Q2. Describe the graph?

• Panel A: Low frequency → separate twitches with full relaxation
• Panel B: Higher frequency (stimuli at PS-PC1, PC2) → incomplete tetanus (partial fusion)
• Panel C: Very high frequency → complete tetanus (smooth sustained contraction)

Q3. How to get this graph?

• Increase frequency of stimuli gradually
• At 10/sec → wave summation
• At 30–50/sec → incomplete tetanus
• At >50/sec → complete tetanus (smooth sustained contraction)

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📄 PAGE 4 - Graph 1 (Multiple fine curves, 1-70 labeled, Point of stimulus, Time tracing 100Hz)

Q1. Identify the graph?

Q2. Describe the graph?

• Many curves labeled 1–70 (from thin small to large)
• A = Point of stimulus
• Low numbers (1, 2, 3) = small stimuli → small contractions
• Higher numbers (10, 20, 30…70) = stronger stimuli → bigger contractions
• Muscle as a whole shows graded response due to recruitment of more motor units

Q3. How to get this graph?

• Apply stimuli from threshold to supramaximal progressively
• Record each contraction
• Graph shows graded recruitment of motor units

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📄 PAGE 4 - Graph 2 (PS, PC₁, PC₂, PR₁, PR₂, curves A and B)

Q1. Identify the graph?

Q2. Describe the graph?

• PS = first stimulus → full twitch
• PC₁ = second stimulus during contraction → no response (absolute refractory period)
• PC₂ = second stimulus slightly later → small response
• PR₁, PR₂ = stimuli during relaxation → partial then full response (relative refractory period)
• A = first twitch | B = small second twitch

Q3. How to get this graph?

• Apply two stimuli at varying intervals
• First stimulus during contraction = no response (ARP)
• Stimulus during relaxation = reduced response (RRP)
• Stimulus after full recovery = normal response

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📄 PAGE 5 - Graph 1 (Curves labeled 0, 10, 20...80, three rows A, B, C)

Q1. Identify the graph?

Q2. Describe the graph?

• Row A: Multiple overlapping curves with numbers 0–80 (different lengths/conditions)
• Row B: Curves at different muscle lengths
• Row C: Inverted curves (showing fatigue or temperature effect)
• Shows how temperature or muscle length affects contraction height

Q3. How to get this graph?

• Vary muscle temperature or initial length
• Record contractions at each condition
• Shows optimal length/temperature for maximum contraction

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📄 PAGE 5 - Graph 2 (MB markings: MB 26, 23, 21, 18, 15, 12, 9, 6, 3, 0 cm)

Q1. Identify the graph?

Q2. Describe the graph?

• X-axis = Muscle-bone distance (MB in cm) = muscle length
• Y-axis = Height of contraction
• At very short length (MB 0 cm) = large contraction
• As length increases → contraction height increases, peaks at optimal length
• Beyond optimal → contraction height falls
• Demonstrates Starling's Law: Contraction strength increases with stretch up to optimal length

Q3. How to get this graph?

• Use frog gastrocnemius
• Change the distance between muscle and bone (stretch the muscle)
• Apply maximal stimulus at each length
• Record height of contraction at each length

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📄 PAGE 6 - Graph 1 (A, B, C sections; g = length, f = force)

Q1. Identify the graph?

Q2. Describe the graph?

• Section A: Increasing stimulus strength → increasing contractions (recruitment)
• Section B: At optimal length → maximum force
• Section C: Muscle stretched beyond optimal → force decreases
• g = length axis, f = force/contraction axis
• Shows that there is an optimal length at which maximum tension is generated (due to maximum actin-myosin overlap)

Q3. How to get this graph?

• Same as above - vary muscle length and record force
• Maximum overlap of actin and myosin = maximum contraction

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📄 PAGE 6 - Graph 2 (dark, two smooth bell-shaped curves together)

Q1. Identify the graph?

Q2. Describe the graph?

• Two overlapping bell-shaped curves
• Second is slightly larger than first
• Shows mechanical summation when second stimulus applied before full relaxation

Q3. How to get this graph?

• Apply two stimuli close together
• Second stimulus during relaxation phase of first

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📄 PAGE 7 - Graph 1 (Bars at 10g–90g on X-axis)

Q1. Identify the graph?

Q2. Describe the graph?

• X-axis = Load applied (10g to 90g)
• Y-axis = Height of contraction
• Small loads (10g, 20g) → tall contractions
• As load increases → contraction height decreases
• At very heavy load (80g, 90g) → muscle cannot lift → no contraction visible (isometric)
• Shows inverse relationship between load and contraction height

Q3. How to get this graph?

• Apply different weights (10g, 20g... 90g) to frog gastrocnemius
• Apply maximal stimulus at each load
• Record height of shortening

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📄 PAGE 7 - Graph 2 (A, B, C rows with subwaves a, b, c, d)

Q1. Identify the graph?

Q2. Describe the graph?

• Row A: Fresh muscle - regular, tall equal contractions
• Row B: After some stimuli - contractions slightly smaller, slightly irregular
• Row C: Fatigued muscle - contractions a→b→c→d, progressively shorter, wider, incomplete relaxation
• In fatigue: amplitude decreases, duration increases, incomplete relaxation, eventually no response
• Shows progressive fatigue with repeated stimulation

Q3. How to get this graph?

• Apply repeated maximal stimuli continuously to frog gastrocnemius
• Observe gradual decrease in contraction height, increase in duration
• Due to: depletion of energy (ATP, glycogen), accumulation of lactic acid

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📄 PAGE 8 - Graph 1 (Sinus venosus and Ventriculae, Normal → Cold ringer / Warm ringer)

Q1. Identify the graph?

Q2. Describe the graph?

• Normal → Cold ringer → Heart rate decreases (fewer, larger beats)
• Normal → Warm ringer → Heart rate increases (more, smaller beats)

• Normal → Cold ringer → Rate decreases
• Normal → Warm ringer → Rate increases
• Shows that temperature directly affects the pacemaker rate (Van't Hoff's law: each 10°C rise doubles metabolic rate)

Q3. How to get this graph?

• Expose frog heart (in situ)
• Record normal heart beat on kymograph
• Apply cold Ringer's solution → observe slowing
• Wash with normal Ringer → recover
• Apply warm Ringer's solution → observe speeding
• Do same for sinus venosus separately and ventricle

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📄 PAGE 8 - Graph 2 (A and B panels - On sinus venosus / On ventricle, Heat ↑ and Cold with N markers)

Q1. Identify the graph?

Q2. Describe the graph?

• N = Normal beat
• Heat ↑ = rate increases (tachycardia)
• Cold = rate decreases (bradycardia)
• After return to normal temperature, heart rate returns to baseline
• Shows chronotropic effect of temperature on both SV and ventricle

Q3. How to get this graph?

• Record frog heart activity
• Alternate between warm and cold Ringer's solution
• Note recovery of rate when temperature returns to normal

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📄 PAGE 9 - Graph 1 (Normal → 1% CaCl₂ → Normal → 1% KCl → Normal → 1% NaCl)

Q1. Identify the graph?

Q2. Describe the graph?

• Normal beats at baseline
• 1% CaCl₂ (Calcium): Contraction height increases, rate may slightly decrease → positive inotropic effect (stronger beats)
• 1% KCl (Potassium): Heart rate decreases, amplitude decreases → negative chronotropic + inotropic effect → can cause cardiac arrest in diastole
• 1% NaCl (Sodium): No significant change (maintains tonicity)
• Recovery to normal with each washout

Q3. How to get this graph?

• Record normal frog heart contractions
• Apply each ion solution separately (1 ml each)
• Record effect, then wash with normal Ringer's between each

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📄 PAGE 9 - Graph 2 (Normal → Adrenaline 1:100000 → Normal → A-Ch 1:1000000)

Q1. Identify the graph?

Q2. Describe the graph?

• Normal baseline beats
• Adrenaline (1:100,000): Beat height increases (positive inotropic) + rate increases (positive chronotropic)
• Recovery to normal
• ACh (Acetylcholine) (1:1,000,000): Beat height decreases (negative inotropic) + rate decreases (negative chronotropic)
• Shows sympathetic vs parasympathetic effects on heart

Q3. How to get this graph?

• Record normal frog heart on kymograph
• Apply adrenaline → record effect → wash with Ringer's
• Apply ACh → record effect → wash with Ringer's

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📄 PAGE 10 - Graph 1 (Same as page 9 graph 1 - clearer version: CaCl₂, KCl, NaCl)

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📄 PAGE 10 - Graph 2 (Normal → Adrenaline 0.5mL → Normal → ACh 0.5mL → Normal)

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📄 PAGE 11 - Graph (Vagal stimulation with muscarinic/nicotinic, Nicotine, Atropine panels A, B, C)

Q1. Identify the graph?

Q2. Describe the graph?

• Vagal stimulation (muscarinic receptors) → heart slows/stops
• Crescent ganglion stimulation (nicotinic) → heart slows (relay via vagal pathway)

• Nicotine blocks nicotinic receptors in ganglion
• Vagal stimulation = still slows heart (post-ganglionic muscarinic intact)
• Crescent ganglion stimulation = no effect (blocked by nicotine)

• Atropine blocks muscarinic receptors
• Vagal stimulation = no effect (blocked)
• Crescent ganglion stimulation = no effect (blocked)
• Shows vagal pathway: Nicotinic (ganglion) → Muscarinic (heart)

Q3. How to get this graph?

• Stimulate vagus nerve directly + stimulate crescent ganglion
• Record effects before and after nicotine/atropine
• Demonstrates acetylcholine receptors in autonomic pathway

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📄 PAGE 11 - Graph 2 (A and B panels: Vagal stimulation + WCL with A/B/C labels)

Q1. Identify the graph?

Q2. Describe the graph?

• Normal → Vagal stimulation → Heart slows/stops
• WCL (Wedensky Complete Lock) with A (ACh) → more slowing
• WCL with A (still ACh) → inhibition then vagal escape (heart beats again despite vagal stimulation)

• With B (Atropine) → Vagal stimulation has no effect (blocked)
• With C (Adrenaline) → Vagal stimulation partially blocked (sympathetic overcomes)
• Shows vagal escape: when vagal stimulation is prolonged, AV node takes over and heart resumes beating (idioventricular rhythm)

Q3. How to get this graph?

• Stimulate vagus nerve continuously
• Initially heart stops, then after some time it escapes and beats again
• This is vagal escape due to: decreased sensitivity of SA node, AV node acts as pacemaker

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📄 PAGE 12 - Graph 1 (Rapid small beats → progressively fewer large beats → very few large beats)

Q1. Identify the graph?

Q2. Describe the graph?

• Left: Normal rapid heart rate (sinus rhythm, small beats)
• Middle: Stimulation of vagus → heart rate slows dramatically, beats become large (8 uppm noted)
• Right: Only 4-5 large slow beats = vagal escape (idioventricular rhythm, ~16 uppm)
• Shows complete vagal inhibition → escape rhythm

Q3. How to get this graph?

• Expose frog heart
• Stimulate vagus nerve strongly and continuously
• Record on kymograph: initial inhibition then slow escape beats

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📄 PAGE 12 - Graph 2 (Letters E and C marked on heart beat tracing)

Q1. Identify the graph?

Q2. Describe the graph?

• Normal beats leading up to point C
• C = Extra stimulus applied → Extrasystole (extra beat) at point E
• After the extrasystole → compensatory pause (longer gap before next normal beat)
• The total interval (extrasystole + compensatory pause) = 2 normal intervals
• This demonstrates the refractory period and compensatory pause of the heart

Q3. How to get this graph?

• Record normal frog heart on kymograph
• Apply an extra single stimulus during the diastolic interval
• A premature beat (extrasystole) occurs
• Followed by a compensatory pause (next normal beat is delayed)

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📄 PAGE 13 - Graph (Subthreshold, Threshold, Maximal, Supra-maximal + Signal marker)

Q1. Identify the graph?

Q2. Describe the graph?

• Subthreshold: No response (flat line)
• Threshold: First visible small contraction
• Maximal: Full contraction (same height as threshold in heart = maximum)
• Supra-maximal: Same height as maximal (no increase)
• This shows the All-or-None law of the heart: Heart contracts maximally or not at all; supra-maximal stimulus gives no bigger response

Q3. How to get this graph?

• Apply stimuli of increasing strength to frog heart
• Record contractions
• Shows that once threshold is crossed, response is always maximal regardless of stimulus strength

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📄 PAGE 13 - Graph 2 (Three rows with wave patterns of different sizes)

Q1. Identify the graph?

Q2. Describe the graph?

• Top row: Fast small beats (normal rate)
• Middle row: Larger, slower beats
• Bottom row: Largest, slowest beats
• Shows that heart beats at different rates/amplitudes respond differently
• Could represent Treppe or frequency-force relationship

Q3. How to get this graph?

• Stimulate frog heart at different frequencies
• Record corresponding contraction patterns

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📄 PAGE 14 - Graph (Normal cardiogram → Vagal stimulation → Vagal escape / Idio-ventricular rhythm)

Q1. Identify the graph?

Q2. Describe the graph?

• Normal cardiogram: Regular rapid beats (sinus rhythm)
• Vagal stimulation: Heart slows and stops (complete inhibition of SA node)
• Vagal escape (Idioventricular rhythm): Heart beats again spontaneously at a slow rate (~30/min)
• These slow beats arise from the AV node or ventricular pacemaker (lower pacemaker takes over)

Q3. How to get this graph?

• Record normal frog heart beat
• Apply continuous strong vagal stimulation
• After a pause, the heart resumes slowly = vagal escape
• Shows automaticity of lower pacemakers

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📄 PAGE 14 - Graph 2 (Regular beats changing at point 2 to larger irregular beats)

Q1. Identify the graph?

Q2. Describe the graph?

• Normal regular beats (1)
• At point 2: Extra stimulus applied → premature beat (extrasystole)
• After extrasystole → compensatory pause (longer gap)
• Next beat returns to normal rhythm
• Shows the refractory period of cardiac muscle and compensatory mechanism

Q3. How to get this graph?

• Record normal frog heart
• Apply a single extra stimulus during diastolic interval (not during systole)
• A premature contraction appears → followed by compensatory pause
• Note: Stimulus during systole (refractory period) = no response

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⚡ QUICK SUMMARY TABLE - All Graphs at a Glance

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