# -*- coding: utf-8 -*-
from reportlab.lib.pagesizes import A4
from reportlab.lib.units import cm
from reportlab.lib import colors
from reportlab.platypus import SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, PageBreak, KeepTogether
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.enums import TA_LEFT, TA_CENTER

def esc(s):
    s = s.replace("&", "&amp;").replace("<", "&lt;").replace(">", "&gt;")
    s = s.replace("[[B]]", "<b>").replace("[[/B]]", "</b>")
    s = s.replace("->", "&rarr;" if False else "->")
    s = s.replace(u"\u2191", "(inc.)").replace(u"\u2193", "(dec.)")
    return s

styles = getSampleStyleSheet()

title_style = ParagraphStyle("title2", parent=styles["Title"], fontSize=20, spaceAfter=4, textColor=colors.HexColor("#0b3d91"))
subtitle_style = ParagraphStyle("subtitle", parent=styles["Normal"], fontSize=11, alignment=TA_CENTER, textColor=colors.HexColor("#444444"), spaceAfter=14)
section_style = ParagraphStyle("section", parent=styles["Heading1"], fontSize=15, textColor=colors.white, backColor=colors.HexColor("#0b3d91"), spaceBefore=10, spaceAfter=8, leftIndent=6, borderPadding=(6,6,6,6))
q_style = ParagraphStyle("q", parent=styles["Normal"], fontSize=10.3, fontName="Helvetica-Bold", textColor=colors.HexColor("#1a1a1a"), spaceBefore=8, spaceAfter=2, leading=13)
a_style = ParagraphStyle("a", parent=styles["Normal"], fontSize=10, fontName="Helvetica", textColor=colors.HexColor("#7a0000"), leftIndent=10, spaceAfter=1, leading=13, backColor=colors.HexColor("#fff3cd"), borderPadding=(4,4,4,4))
sup_style = ParagraphStyle("sup", parent=styles["Normal"], fontSize=9, fontName="Helvetica-Oblique", textColor=colors.HexColor("#333333"), leftIndent=10, spaceAfter=6, leading=11.5)

def P(text, style):
    return Paragraph(esc(text), style)

# ---------------------------------------------------------------------------
# DATA: (system_name, [ (question, key_highlight_line, extra_short_note_or_None), ... ])
# key_highlight_line = the exact examiner-scoring one-liner (kept short, bold+highlighted)
# extra = optional 1-line supporting point (only where needed for 3-mark completeness)
# ---------------------------------------------------------------------------

DATA = []

DATA.append(("RENAL SYSTEM", [
("What if GFR decreases suddenly? Effect on urine production?",
 "GFR (dec.) -> less filtrate reaches tubules -> oliguria/anuria; urea & creatinine retained (azotemia).",
 "RAAS activates to compensate for the fall in filtration."),
("What if renal blood flow increases significantly? Effect on GFR and urine production?",
 "RBF (inc.) -> GFR (inc.) within autoregulatory range -> increased urine output (diuresis).",
 "Beyond autoregulatory limits, GFR rises in parallel with RBF."),
("What if ADH levels increase excessively? Effect on water reabsorption and urine concentration?",
 "ADH (inc.) -> more aquaporin-2 channels in collecting duct -> more water reabsorption -> concentrated, low volume urine (dilutional hyponatremia as in SIADH).", None),
("What if aldosterone levels decrease significantly? Effect on sodium reabsorption and potassium secretion?",
 "Aldosterone (dec.) -> less Na+ reabsorption & less K+ secretion in DCT/collecting duct -> hyponatremia + hyperkalemia (as in Addison's disease).", None),
("What if the renal tubules are damaged? Effect on electrolyte balance and acid-base balance?",
 "Tubular damage -> impaired reabsorption/secretion -> electrolyte imbalance (hyperkalemia) and metabolic acidosis (failure of H+ secretion/HCO3- reabsorption) = Renal Tubular Acidosis.", None),
("Why does the renal blood flow increase during high-sodium diet?",
 "High Na+ delivery to macula densa -> tubuloglomerular feedback -> afferent arteriole dilates -> RBF & GFR increase to excrete the Na+ load (pressure natriuresis).", None),
("Why does the aldosterone secretion increase during low-sodium diet?",
 "Low Na+ -> ECF volume/BP falls -> renin-angiotensin-aldosterone system (RAAS) activated -> aldosterone rises to conserve Na+.", None),
("Why does the pH of urine decrease during acidosis?",
 "Acidosis -> kidney increases H+ secretion (Type-A intercalated cells) and NH4+/titratable acid excretion to restore acid-base balance -> urine becomes more acidic.", None),
("Why does the blood pressure increase during renal failure?",
 "Renal failure -> Na+/water retention + RAAS activation + failure to excrete pressor substances -> hypertension.", None),
("Why does the acid-base balance change during renal failure?",
 "GFR/nephron loss -> reduced H+ excretion & reduced HCO3- regeneration -> acids accumulate -> metabolic acidosis (high anion gap).", None),
("Why does the renal medulla play a crucial role in concentrating urine?",
 "Medullary hyperosmotic gradient (countercurrent multiplication in loop of Henle + countercurrent exchange in vasa recta) draws water out of collecting duct under ADH -> concentrated urine.", None),
("PCT has a high rate of O2 consumption, explain why?",
 "PCT reabsorbs ~65-70% of filtrate (Na+, glucose, amino acids) by active Na-K-ATPase transport -> high ATP demand -> high O2 consumption.", None),
("High resistance is offered to blood flow in efferent arteriole, explain why?",
 "Narrow efferent arteriole with smooth muscle tone maintains glomerular capillary hydrostatic pressure needed for filtration, and creates the pressure drop that supplies peritubular capillaries for reabsorption.", None),
("Medullary blood flow does not show autoregulation, why?",
 "Vasa recta lack myogenic/tubuloglomerular feedback mechanisms of cortical vessels; flow must stay low & constant to avoid washing out the medullary osmotic gradient.", None),
("Renal failure develops in persons with poor renal perfusion, why?",
 "Reduced perfusion -> GFR falls -> ischemic acute tubular necrosis (pre-renal progressing to intrinsic renal failure) once autoregulation fails (MAP <80 mmHg).", None),
("Chronic renal disease produces anemia, explain how?",
 "Damaged kidney -> reduced erythropoietin production -> reduced RBC production in marrow -> normocytic normochromic anemia.", None),
("Predicted renal threshold for glucose is more than the actual value, explain why?",
 "\"Splay\" - nephron heterogeneity in Tm for glucose - some nephrons saturate earlier than others, so glucose appears in urine before the calculated (predicted) threshold is reached.", None),
("Angiotensin II plays an important role in the body's response to hypovolemia, explain how?",
 "Angiotensin II: potent vasoconstrictor (raises TPR/BP), stimulates aldosterone (Na+/water retention), stimulates thirst & ADH, constricts efferent arteriole (maintains GFR) - restores blood volume and BP.", None),
("Increase in ANP secretion leads to natriuresis, explain how?",
 "Atrial stretch -> ANP release -> dilates afferent & constricts efferent arteriole (GFR inc.), inhibits Na+ reabsorption in collecting duct, and suppresses renin/aldosterone/ADH -> natriuresis + diuresis.", None),
("Hemoglobin is an important buffer system in the body, explain how?",
 "Hb has histidine imidazole groups (pKa near physiological pH); deoxy-Hb buffers H+ generated from CO2 hydration in tissues, enabling CO2 transport with minimal pH change (isohydric transport).", None),
("There is increased frequency of micturition during nervousness, why?",
 "Anxiety alters cortical/autonomic input to the micturition reflex, lowering the detrusor stretch-reflex threshold -> bladder contracts at smaller volumes -> urgency & frequency.", None),
("High protein diet increases the ability of kidney to concentrate the urine, explain how?",
 "Protein catabolism -> more urea produced -> urea recycling (UT-A transporters) in inner medulla adds to medullary hyperosmolarity -> enhances the concentrating mechanism.", None),
("Albuminuria occurs in nephrotic syndrome, explain why?",
 "Damage to glomerular filtration barrier (podocyte effacement, loss of GBM negative charge) -> increased permeability to plasma proteins -> heavy albuminuria.", None),
("Splay in glucose titration curve, explain why?",
 "Nephron heterogeneity in Tm for glucose - not all nephrons saturate simultaneously -> a gradual rounded curve near threshold instead of a sharp cut-off.", None),
("Hyperosmolarity in medullary interstitium is important component during concentration of urine, why?",
 "It creates the osmotic gradient that pulls water out of the collecting duct (under ADH, via aquaporins) as urine passes through the medulla -> concentrated urine.", None),
("Plateau phase occurs in cystometrogram, explain why?",
 "Reflects a strong, sustained detrusor contraction of the micturition reflex that maintains high intravesical pressure until the bladder is fully emptied.", None),
("Renal medulla is exposed to hypoxic damage more than cortex, explain why?",
 "Medulla gets only ~1-2% of total renal blood flow yet has high O2 demand (active transport in thick ascending limb) -> operates near hypoxic limit -> vulnerable to ischemic injury.", None),
("PAH is used to determine the renal blood flow, explain why?",
 "PAH is almost completely removed from plasma in a single pass (filtered + secreted, ~90% extraction) -> its clearance approximates effective renal plasma flow, used to calculate RBF.", None),
]))

DATA.append(("CARDIOVASCULAR SYSTEM", [
("If the sinoatrial (SA) node is damaged? How would it affect heart rate?",
 "AV node takes over as pacemaker (escape rhythm) -> heart rate falls to ~40-60 bpm (nodal rhythm).", None),
("What if the atrioventricular (AV) node is blocked? How would it affect cardiac conduction?",
 "Complete heart block - atria and ventricles beat independently; ventricles driven by their own slow intrinsic pacemaker (~20-40 bpm) -> bradycardia, risk of Stokes-Adams attacks.", None),
("What if the peripheral resistance increases suddenly? How would it affect blood pressure?",
 "TPR (inc.) -> BP (inc.) [MAP = CO x TPR], mainly raising diastolic BP -> hypertension.", None),
("What if the cardiac output decreases significantly? How would it affect tissue perfusion?",
 "CO (dec.) -> reduced tissue perfusion/O2 delivery -> hypotension, reflex sympathetic activation, risk of organ ischemia/shock.", None),
("What if the sympathetic tone increases suddenly? How would it affect heart rate and blood pressure?",
 "Sympathetic (inc.) -> HR & contractility increase, vasoconstriction -> CO and TPR both rise -> BP increases.", None),
("What if the parasympathetic tone increases suddenly? How would it affect heart rate and blood pressure?",
 "Vagal tone (inc.) -> HR falls (ACh acts on SA node) -> CO falls -> mild fall in BP (vagus has little direct effect on vessels).", None),
("Why does the heart rate and blood pressure increase during exercise?",
 "Central command + muscle chemo/mechanoreceptors -> sympathetic (inc.)/vagal (dec.) -> HR and contractility increase -> CO increases enough to raise BP despite muscle vasodilation.", None),
("Why does the blood flow to the skeletal muscle increase during exercise?",
 "Local metabolites (CO2, K+, adenosine, H+, lactate) accumulate -> active/metabolic hyperemia -> local arteriolar vasodilation overriding sympathetic vasoconstriction.", None),
("Why does the pulmonary vascular resistance increase during high altitude?",
 "Alveolar hypoxia -> hypoxic pulmonary vasoconstriction (unique to lung vessels) -> PVR increases -> chronic exposure causes pulmonary hypertension.", None),
("Bradycardia is observed in raised intracranial tension, give reasons.",
 "Raised ICP -> cerebral ischemia -> Cushing reflex: sympathetic surge raises BP to maintain cerebral perfusion -> baroreceptors then trigger reflex bradycardia (Cushing's triad).", None),
("Tachycardia is seen usually with old age, give reasons.",
 "Aging -> reduced vagal tone/baroreceptor sensitivity and fewer SA-node cells -> relatively higher resting heart rate.", None),
("What is physiological hypertrophy of the left ventricle, give reasons.",
 "Chronic increased workload (e.g. athletes) -> compensatory increase in myocardial fiber size (not number) -> improved contractile efficiency without pathological fibrosis.", None),
("Heart sounds are not produced during opening of valves, why?",
 "Valve opening is passive, gradual and low-velocity; heart sounds need turbulence from sudden valve closure and abrupt deceleration/acceleration of blood, not smooth opening.", None),
("Myocardium is well perfused during diastole, give reasons.",
 "Systolic contraction compresses intramural coronary vessels (esp. LV subendocardium) and cuts flow; in diastole the myocardium relaxes, vessels open -> most coronary flow occurs in diastole.", None),
("Fainting occurs during emotions, explain why?",
 "Strong emotion -> sudden vagal surge + sympathetic withdrawal -> bradycardia + vasodilation -> BP falls -> reduced cerebral perfusion -> vasovagal syncope.", None),
("The thin walled and delicate capillaries are less prone to rupture, explain why?",
 "By Laplace's Law (Tension = Pressure x radius), the very small radius and low pressure of capillaries keep wall tension low despite the thin wall -> resistant to rupture.", None),
("Dilated heart has to do more work than a non-dilated heart, give reasons.",
 "By Laplace's Law (T = P x r), a dilated ventricle needs more wall tension to generate the same pressure -> more energy/O2 per stroke -> less efficient pump.", None),
("Why veins are called capacitance vessels?",
 "Veins are thin-walled, highly distensible and hold ~60-70% of total blood volume with little pressure change -> act as the blood reservoir (capacitance) of circulation.", None),
("Variation in arteriolar diameter has marked effect on the systolic blood pressure, why?",
 "By Poiseuille's law, resistance varies inversely with r^4, so small changes in arteriolar radius greatly change TPR -> mainly alters diastolic BP (peripheral run-off); systolic BP depends more on stroke volume/aortic compliance.", None),
("Cardiac muscle cannot be tetanized/Cardiac muscle shows no signs of fatigue, explain why?",
 "Long refractory period (~250 ms), almost equal to contraction duration, prevents summation/tetanization; continuous aerobic perfusion prevents fatigue.", None),
("Atrial and ventricular muscles do not show autorhythmicity, explain why?",
 "Working (contractile) myocardial cells have a stable resting membrane potential, unlike nodal tissue which has an unstable, leaky RMP (funny current) -> need an external stimulus to fire.", None),
("During BP measurements, systolic BP should be first measured by palpatory method, why?",
 "To detect the auscultatory gap (a silent period in Korotkoff sounds) so the systolic pressure is not underestimated when cuff inflation is set using auscultation alone.", None),
("Heart rate increases in inspiration, give explanation.",
 "Inspiration -> intrathoracic pressure falls -> venous return increases -> atrial stretch (Bainbridge reflex) + reduced vagal tone -> HR rises (respiratory sinus arrhythmia).", None),
("Explain why there is Increased stroke volume during exercise.",
 "Venous return increases (muscle & respiratory pump) -> EDV rises (Frank-Starling law) + sympathetic contractility increases + ESV falls -> stroke volume increases.", None),
("Pressing the carotid sinus increases the heart rate, give reasons.",
 "Correction: carotid sinus pressure stretches baroreceptors -> increased vagal & decreased sympathetic outflow -> reflex BRADYCARDIA and fall in BP (baroreceptor/carotid sinus reflex), not an increase.", None),
("Extracellular concentration of calcium influences the force of conduction in cardiac muscle, explain why?",
 "Cardiac contraction depends on calcium-induced calcium release; extracellular Ca2+ entering via L-type channels during the plateau triggers greater SR Ca2+ release -> force of contraction is directly proportional to extracellular Ca2+.", None),
("Cold clammy skin and rapid pulse occurs in hypovolemic shock, give reasons.",
 "Reduced blood volume/BP -> baroreceptor reflex -> intense sympathetic vasoconstriction diverts blood from skin/splanchnic bed to vital organs -> cold, clammy skin; reflex tachycardia maintains CO.", None),
("Body of a patient in shock should not be covered with blanket, why?",
 "Warming causes cutaneous vasodilation, diverting blood away from vital organs, and raises metabolic O2 demand -> worsens hypoperfusion in shock.", None),
]))

DATA.append(("RESPIRATORY SYSTEM", [
("What if a person has a blocked airway? How would it affect their breathing rate and blood gases?",
 "Obstruction -> ventilation falls -> CO2 rises (hypercapnia) & O2 falls (hypoxemia) -> chemoreceptors stimulated -> rate/effort of breathing increases (dyspnea); complete block -> rapid hypoxia.", None),
("What if a person has a chest injury that causes pneumothorax? How would it affect their breathing rate and blood oxygen levels?",
 "Air enters pleural space -> negative intrapleural pressure lost -> lung collapses -> V/Q mismatch -> hypoxemia -> reflex tachypnea.", None),
("Why do we have a higher breathing rate when we exercise?",
 "Increased CO2 production and metabolic acids stimulate central & peripheral chemoreceptors, plus feed-forward cortical/proprioceptive drive -> ventilation matches metabolic demand.", None),
("Why do people at high altitude often experience hypoxia?",
 "Low barometric pressure -> low pO2 in inspired air -> low alveolar & arterial pO2 despite normal 21% O2 -> hypoxic hypoxia.", None),
("Why do scuba divers need to breathe in compressed air when they dive deep underwater?",
 "Ambient pressure rises with depth (~1 atm/10 m); to keep the chest expanded and alveoli open against this pressure, inspired air must be delivered at a matching high pressure.", None),
("Intrapleural pressure is always negative/subatmospheric, why?",
 "Opposing elastic recoil - lungs pull inward, chest wall springs outward - creates a sub-atmospheric pressure in the pleural fluid that keeps the lungs adherent to the chest wall.", None),
("Pulmonary Tuberculosis affects apex of lung first, why?",
 "Apex has the highest V/Q ratio (best oxygenation) but least blood flow/lymphatic drainage -> favors growth of the obligate aerobic M. tuberculosis.", None),
("Expiratory phase is longer than inspiratory phase of respiratory cycle, why?",
 "Inspiration is active (muscular contraction); expiration is largely passive elastic recoil, which takes longer than active contraction -> I:E ratio ~1:2.", None),
("Bronchial asthma is a disease of expiratory obstruction, explain why?",
 "Inflammation/bronchoconstriction narrows airways; during expiration, dynamic airway compression further collapses the narrowed airways -> greater obstruction on expiration -> wheeze & air trapping.", None),
("High V/P ratio is observed in the apices of lungs, explain why?",
 "Gravity reduces blood flow (Q) at the apex much more than ventilation (V) -> V/Q ratio is highest (~3) at apex, lowest (~0.6) at base.", None),
("Compliance of lungs with thorax is greater than the compliance of lung alone, why?",
 "Correction: combined lung+thorax compliance is actually LESS than either alone, since 1/C(total) = 1/C(lung) + 1/C(thorax) - combining two elastic structures in series reduces overall compliance.", None),
("Arterial pO2 is less than alveolar pO2, give reasons.",
 "Physiological shunt (bronchial + thebesian venous admixture) and slight V/Q mismatch create the normal A-a O2 gradient (~5-10 mmHg).", None),
("Oxygen-hemoglobin dissociation curve is sigmoid shape, explain why?",
 "Cooperative binding - binding of the first O2 increases Hb's affinity for subsequent O2 (heme-heme interaction) -> steep middle, flat ends -> sigmoid curve.", None),
("Myoglobin acts as a temporary O2 storehouse, explain why?",
 "Myoglobin has a higher O2 affinity than Hb (hyperbolic curve) - loads O2 easily but releases it only at very low pO2 during muscle activity -> acts as an O2 reservoir.", None),
("Blood is an ideal vehicle for O2 transport, why?",
 "Hemoglobin in RBCs raises O2 carrying capacity ~70-fold over plasma alone, transporting large amounts of O2 without a big rise in pO2.", None),
("Central chemoreceptors respond only to abrupt changes in pCO2, give reasons.",
 "In sustained hypercapnia, the choroid plexus adjusts CSF HCO3- to normalize pH over 1-2 days, blunting the response; only a sudden pCO2 rise causes an acute CSF pH fall and strong stimulation.", None),
("Respiratory chemoreceptors are not stimulated in anemia or CO poisoning, why?",
 "Peripheral chemoreceptors sense pO2 (partial pressure), not O2 content; in anemia/CO poisoning pO2 stays normal even though O2 carrying capacity/content is low -> hypoxia goes undetected.", None),
("Mild-to-moderate hypoxia stimulates the respiration but severe hypoxia depresses it, why?",
 "Mild hypoxia stimulates peripheral chemoreceptors -> ventilation rises; severe hypoxia directly depresses the respiratory center neurons themselves, overriding chemoreceptor drive.", None),
("Pulmonary ventilation is not much affected until pO2 of inspired air falls below 60 mm Hg, explain why?",
 "The O2-Hb curve is flat above pO2 60 mmHg (saturation stays >90%) -> minimal fall in O2 content until pO2 drops below 60 mmHg (steep part of curve) triggers chemoreceptors.", None),
("CO2 increases pulmonary ventilation primarily by stimulating central chemoreceptors. Explain how?",
 "CO2 diffuses freely into CSF -> combines with H2O -> H2CO3 -> H+ + HCO3- -> the H+ directly stimulates central chemoreceptors (CO2 itself, not blood H+, crosses the blood-brain barrier).", None),
("Apnea occurs after voluntary hyperventilation, explain how?",
 "Hyperventilation washes out CO2 -> pCO2 falls below the apneic threshold -> removes the main chemoreceptor drive to breathe -> transient apnea until CO2 re-accumulates.", None),
("Cyanosis is not seen in anemic hypoxia, why?",
 "Cyanosis needs >=5 g/dL of desaturated Hb in capillary blood; in severe anemia total Hb is low, so this absolute threshold of reduced Hb is rarely reached.", None),
("Cyanosis is a common occurrence in hypoxic hypoxia, why?",
 "Low arterial pO2 -> low Hb saturation -> large absolute amount of reduced Hb (>5 g/dL) in capillaries -> visible bluish discoloration.", None),
("Histotoxic hypoxia cannot cause cyanosis, why?",
 "In histotoxic hypoxia (e.g. cyanide poisoning) O2 delivery and Hb saturation stay normal (tissues fail to use O2) -> blood stays well oxygenated (bright red) -> no cyanosis.", None),
("Babies of diabetic mothers are prone to develop IRDS, why?",
 "Maternal hyperglycemia -> fetal hyperinsulinemia -> insulin antagonizes cortisol's stimulation of surfactant synthesis by type II pneumocytes -> delayed lung maturation -> risk of IRDS.", None),
("Systemic circulation has a low pO2 than pulmonary circulation, why?",
 "(Concept intended: pulmonary circulation is a LOW-PRESSURE system) - pulmonary vessels are short, thin-walled, highly distensible with a large cross-sectional area -> same CO delivered at much lower pressure (~15 mmHg) than systemic (~93 mmHg).", None),
("In venous blood, RBCs have higher hematocrit than in arterial, explain why?",
 "At tissue capillaries, fluid filters into the interstitium, slightly concentrating the cellular fraction by the venous end -> marginally higher venous hematocrit.", None),
("Lesions in Inspiratory (I) neurons does not abolish respiratory activity, why?",
 "The basic respiratory rhythm arises from an intrinsic pacemaker network (pre-Botzinger complex), a distributed/redundant circuit - not solely from I-neurons - so localized lesions don't stop rhythmicity.", None),
("Increase in H+ ion concentration in blood cannot activate central chemoreceptors, explain why?",
 "H+ ions are charged and cannot cross the blood-brain barrier readily; only lipid-soluble CO2 crosses freely and generates H+ locally in CSF to stimulate central chemoreceptors.", None),
("O2-N2 mixture is used in SCUBA, explain why?",
 "Standard air (O2-N2) avoids O2 toxicity at depth and is economical/safe for moderate depths; N2 use is limited at greater depths by nitrogen narcosis and decompression sickness.", None),
("Relief of orthopnea occurs on sitting up, explain how?",
 "Sitting up -> gravity pools blood in the lower body -> reduces venous return to lungs -> reduces pulmonary congestion -> improves ventilation and relieves breathlessness.", None),
("Headache is experienced while staying in an overcrowded room for long time, explain why?",
 "Poor ventilation -> CO2 accumulates (hypercapnia) -> CO2 is a potent cerebral vasodilator -> cerebral blood flow/ICP rises -> headache (mild hypoxia also contributes).", None),
("Severe joint pain occurs in decompression sickness, how?",
 "Rapid ascent -> sudden fall in ambient pressure -> dissolved N2 (accumulated at depth) comes out of solution as gas bubbles in blood/tissues, especially joints -> obstructs microcirculation, distends tissue -> severe joint pain (\"the bends\").", None),
]))

DATA.append(("GASTROINTESTINAL SYSTEM (GIT)", [
("What if a person has a vagotomy (cutting of the vagus nerve)? How would this affect gastric acid secretion and gastrointestinal motility?",
 "Loss of vagal (ACh) drive to parietal/G cells -> reduced gastric acid secretion and reduced gastric motility (delayed emptying) - used therapeutically in peptic ulcer.", None),
("What if a person has a pancreatic insufficiency? How would this affect nutrient digestion and absorption in the small intestine?",
 "Loss of pancreatic lipase/amylase/trypsin -> maldigestion of fat, starch, protein -> steatorrhea, malabsorption, fat-soluble vitamin deficiency.", None),
("What if a person has a liver disease that impairs bile production? How would this affect fat digestion and absorption in the small intestine?",
 "Reduced bile salts -> impaired micelle formation -> reduced fat emulsification/absorption -> steatorrhea and fat-soluble vitamin (A,D,E,K) deficiency.", None),
("What if a person has a condition that slows down gastric emptying (e.g., gastroparesis)? How would this affect blood sugar levels after a meal?",
 "Delayed, erratic nutrient delivery to intestine mismatches insulin action -> post-meal hypoglycemia followed by delayed hyperglycemia - erratic glycemic control (problematic in diabetics).", None),
("What if a person has a small intestine bacterial overgrowth (SIBO)? How would this affect nutrient absorption and gastrointestinal symptoms?",
 "Bacteria consume nutrients (esp. B12) and deconjugate bile salts -> malabsorption (fat, B12), bloating, diarrhea, B12-deficiency anemia.", None),
("What if a person has a condition that impairs the release of cholecystokinin (CCK)? How would this affect pancreatic enzyme secretion and gallbladder contraction?",
 "Reduced CCK -> reduced pancreatic enzyme secretion and reduced gallbladder contraction/sphincter of Oddi relaxation -> impaired fat/protein digestion and bile delivery.", None),
("What if a person has a condition that slows down intestinal motility (e.g., constipation)? How would this affect the absorption of nutrients and the growth of gut microbiota?",
 "Prolonged transit -> more contact time can raise water/nutrient absorption, but favors bacterial overgrowth/dysbiosis with excess fermentation and gas.", None),
("Postprandial alkaline tide or alkaline urine is observed after heavy meal why?",
 "Parietal cells secrete H+ into the stomach in exchange for HCO3- pumped into blood (Cl-/HCO3- exchanger) -> transient rise in blood/urine pH after a meal = alkaline tide.", None),
("Bulky, clay colored stools are the features of obstructive jaundice, How?",
 "Bile flow blocked -> no bilirubin/stercobilin reaches gut -> pale/clay colored stool; reduced bile salts -> fat malabsorption -> bulky, greasy stool.", None),
("A patient suffering from aptyalism has high risk of dental caries why?",
 "Saliva's antibacterial (lysozyme, IgA), buffering and cleansing action, and enamel remineralizing minerals are lost -> bacterial overgrowth and acid buildup -> increased caries.", None),
("Steatorrhea occurs in pancreatic insufficiency give reasons.",
 "Reduced pancreatic lipase -> undigested fat passes unabsorbed into stool -> bulky, greasy, foul-smelling stool.", None),
("Gastrin release though vagally mediated is not blocked by atropine -give explanation.",
 "Vagal stimulation releases gastrin from G cells via GRP (a non-cholinergic transmitter), not via ACh/muscarinic receptors -> atropine (muscarinic blocker) cannot block this pathway.", None),
("Gastric mucosa is resistant to autodigestion- give reasons",
 "Protected by the mucus-bicarbonate barrier, tight epithelial junctions, rapid cell turnover, and pepsinogen secreted in an inactive form activated only in the acidic lumen - the gastric mucosal barrier.", None),
("Alcohol intoxication can be avoided if it is consumed after ingestion of a drink rich in fat, how?",
 "Fat delays gastric emptying (CCK-mediated enterogastric reflex) -> slows alcohol delivery to the small intestine (main absorption site) -> lower peak blood alcohol level.", None),
("Duodenal ulcer can be treated by vagotomy- give explanation.",
 "Vagotomy removes the vagal (cephalic phase) drive to acid secretion and gastrin release -> reduces basal & stimulated acid output -> lowers acid-peptic aggression causing the ulcer.", None),
("Resection of large segment of ileum can result in steatorrhea, why?",
 "Terminal ileum is the main site of bile-salt reabsorption; its loss depletes the bile salt pool -> impaired micelle formation/fat absorption -> steatorrhea.", None),
("Achlorhydria is associated with iron deficiency anemia- give reasons.",
 "Gastric HCl reduces dietary Fe3+ to the more absorbable Fe2+ form and frees iron from food proteins; without acid, iron absorption falls -> iron deficiency anemia.", None),
("Ranitidine or Omeprazole is given in peptic ulcer, why?",
 "Ranitidine (H2 blocker) blocks histamine-driven acid secretion; Omeprazole (PPI) directly inhibits the H+/K+ ATPase proton pump - both markedly cut gastric acid, allowing ulcer healing.", None),
("Dizziness is seen after a heavy meal in gastrectomized patient, why?",
 "Loss of pyloric control -> rapid \"dumping\" of hyperosmolar chyme into jejunum -> fluid shifts from plasma into gut (BP falls) + reactive hyperinsulinemia/hypoglycemia -> dizziness (dumping syndrome).", None),
("Rapidly changing movement causes vomiting, why?",
 "Excessive stimulation of the vestibular apparatus sends signals via the vestibulocerebellum to the vomiting center/CTZ in the medulla -> motion sickness/vomiting.", None),
("Loss of fluid from the colon in chronic diarrhea results in severe hypokalemia -give reasons.",
 "Colonic fluid is K+-rich; ongoing loss depletes body K+, and secondary hyperaldosteronism (from volume depletion) further increases renal K+ loss -> hypokalemia.", None),
("Appreciable amounts of faeces continue to be passed during prolonged starvation, give reasons.",
 "Stool is not just undigested food - it contains desquamated intestinal epithelial cells, bacteria (~1/3 of dry weight), and GI secretions (bile pigments, mucus) even without intake.", None),
("Majority of bile reaches circulation, how and why?",
 "Bile salts are efficiently reabsorbed (~95%) in the terminal ileum via active Na+-dependent transport, return to the liver in portal blood and are re-secreted (enterohepatic circulation) - recycled several times per meal.", None),
("Misoprostol given to patients on treatment of arthritis with NSAIDs, why?",
 "Misoprostol (a PGE1 analogue) replaces the protective prostaglandins (mucus/bicarbonate secretion, mucosal blood flow) lost due to NSAID COX inhibition -> protects gastric mucosa from NSAID ulcers.", None),
("Glucose is not formed by the action of salivary amylase on starch, why?",
 "Salivary amylase only breaks internal alpha-1,4 glycosidic bonds, producing maltose/maltotriose/dextrins - it cannot cleave down to glucose; that final step needs brush-border enzymes (maltase etc.).", None),
]))

DATA.append(("GENERAL PHYSIOLOGY", [
("What would happen to the rate of diffusion of a substance across a cell membrane if the surface area of the membrane increased?",
 "By Fick's Law, rate of diffusion is directly proportional to surface area -> increased surface area increases the rate of diffusion.", None),
("How would a decrease in plasma protein concentration affect the distribution of fluid between the intravascular and interstitial compartments?",
 "Reduced plasma albumin -> reduced plasma oncotic pressure -> fluid shifts from intravascular to interstitial space -> edema + relative intravascular volume depletion.", None),
("What would happen to the intracellular fluid volume if a person were to ingest a large amount of salt?",
 "Excess salt raises ECF osmolarity -> water moves out of cells by osmosis into ECF -> intracellular fluid volume decreases (cell shrinkage) until thirst/ADH restore balance.", None),
("How do gap junctions facilitate communication between adjacent cells?",
 "Gap junctions are connexon channels directly linking the cytoplasm of adjacent cells, allowing ions/small molecules/electrical current to pass directly - enabling synchronized activity (e.g. cardiac muscle) without a chemical synapse.", None),
("What would happen to the RMP of a neuron if the concentration of potassium ions (K+) outside the cell increased?",
 "Higher extracellular K+ reduces the K+ concentration gradient -> reduced K+ efflux -> resting membrane potential becomes less negative (depolarized), per the Nernst equation for EK.", None),
("What is the role of the sodium-potassium pump in maintaining the RMP?",
 "Na-K ATPase (electrogenic, 3Na+ out : 2K+ in) maintains the concentration gradients (high intracellular K+, high extracellular Na+) that the resting K+ leak channels depend on to generate the RMP.", None),
("What is the threshold potential for an action potential, and how is it related to the RMP?",
 "Threshold potential is the critical depolarization level (usually ~15 mV less negative than RMP) at which voltage-gated Na+ channels open explosively, triggering an all-or-none action potential.", None),
]))

DATA.append(("BLOOD", [
("What if the body's ability to regulate blood pH levels is impaired? How would this affect blood oxygen transport?",
 "Acidosis shifts the O2-Hb curve right (Bohr effect) -> reduced Hb affinity -> easier O2 unloading at tissues but harder loading at lungs; alkalosis has the opposite effect.", None),
("What if a person's hematocrit level increases significantly due to dehydration? How would this affect blood viscosity and blood flow?",
 "Increased hematocrit steeply raises blood viscosity -> increased resistance to flow -> reduced flow rate and increased cardiac workload.", None),
("What if a patient has a deficiency of clotting factor VIII? How would this affect blood coagulation and the risk of bleeding?",
 "Factor VIII deficiency impairs the intrinsic pathway (IXa-VIIIa complex activating factor X) -> prolonged clotting time (PTT) -> deep tissue/joint bleeding (Hemophilia A).", None),
("What if a person's red blood cell count decreases significantly due to anemia? How would this affect oxygen delivery to the tissues?",
 "Reduced RBC/Hb -> reduced O2-carrying capacity -> reduced O2 delivery -> tissue hypoxia; compensated by increased HR/CO and increased 2,3-DPG (easier O2 unloading).", None),
("What if a patient has a bleeding disorder that affects the function of platelets? How would this affect blood coagulation?",
 "Impaired primary hemostasis (platelet plug formation) -> prolonged bleeding time (BT), but clotting time (CT) stays normal -> mucocutaneous bleeding, petechiae, purpura.", None),
("Why blood does not clot in vivo?",
 "Intact endothelium releases anticoagulant/antiplatelet factors (prostacyclin, NO, heparin-like proteoglycans, thrombomodulin) and natural circulating anticoagulants (antithrombin III, protein C/S) inactivate any stray clotting factors.", None),
("What are the possible mechanisms underlying the improvement or reversal of anemia after undergoing gastrectomy?",
 "Post-gastrectomy anemia (loss of intrinsic factor -> B12 deficiency; achlorhydria -> iron deficiency) improves with parenteral B12 and iron supplementation, bypassing the impaired gastric absorption step.", None),
("How does opsonization aid phagocytosis?",
 "Opsonins (IgG, C3b) coat the pathogen and bind Fc/complement receptors on phagocytes -> greatly enhances recognition, attachment and engulfment of the pathogen.", None),
("Why Aspirin is given in myocardial infarction?",
 "Aspirin irreversibly inhibits COX-1 in platelets -> reduces thromboxane A2 -> reduces platelet aggregation -> limits further coronary thrombus formation/extension.", None),
("Dicumarol cannot be used as an in vitro anticoagulant why?",
 "Dicumarol works only in vivo by inhibiting hepatic synthesis of factors II, VII, IX, X; it has no effect on clotting factors already present in blood already drawn.", None),
("Why in vitamin K deficiency or in liver diseases clotting time is prolonged?",
 "Vitamin K is needed for gamma-carboxylation (activation) of factors II, VII, IX, X made in the liver; its deficiency/liver disease reduces functional factor levels -> prolonged clotting time.", None),
("Why in thrombocytopenic purpuras BT is prolonged but CT remains normal?",
 "Platelets are needed for the platelet plug (primary hemostasis) -> BT prolonged; the coagulation cascade (fibrin formation) is intact -> CT stays normal.", None),
("Reticulocyte count increases after vitamin B12 therapy, why?",
 "B12 corrects the block in erythroblast DNA synthesis -> marrow resumes normal maturation and releases new RBCs (reticulocytes) - the \"reticulocyte crisis\" confirms response.", None),
("Parenteral administration of vitamin B12 is done in pernicious anemia why?",
 "Pernicious anemia is due to lack of intrinsic factor (autoimmune parietal cell destruction) needed for oral B12 absorption -> oral B12 can't be absorbed -> must bypass the gut via parenteral (IM) route.", None),
("Hematocrit value of capillary blood is lower than that of actual blood why?",
 "In small vessels RBCs flow in the axial (central) stream while plasma flows near the wall (plasma skimming/Fahraeus effect) -> capillary sampling picks up relatively more plasma -> falsely lower Hct.", None),
("Edema develops in hypoalbuminemia why?",
 "Reduced plasma albumin -> reduced plasma oncotic pressure -> net filtration force at capillaries increases -> fluid shifts into interstitium -> edema.", None),
("Why there is bleeding tendency in obstructive jaundice?",
 "Bile flow blockage -> no bile salts in gut -> reduced fat and fat-soluble vitamin K absorption -> reduced synthesis of vitamin K-dependent factors (II, VII, IX, X) -> bleeding tendency.", None),
("Bleeding occurs in chronic liver diseases why?",
 "Liver failure -> reduced synthesis of clotting factors and often thrombocytopenia (hypersplenism from portal hypertension) -> bleeding tendency.", None),
("PCV of venous blood is greater than that of arterial blood why?",
 "Fluid filters out of capillaries into the interstitium at the tissue level, slightly concentrating the cellular fraction by the venous side -> marginally higher venous PCV.", None),
("Clot does not spread in the injured vessel after blood coagulation - give reasons",
 "Localization occurs because flowing blood dilutes/removes activated factors away from the injury site, and natural anticoagulants (antithrombin III, protein C/S, prostacyclin from adjacent intact endothelium) confine the clot.", None),
("In a Rh-negative mother carrying a Rh-positive fetus, the first child is usually normal why?",
 "Significant fetomaternal blood mixing mainly occurs at delivery (placental separation) -> mother is sensitized (anti-D forms) only after the first delivery -> first child is usually born unaffected.", None),
("Stored blood is not suitable for transfusing WBCs and platelet to a recipient- give reasons.",
 "WBCs and platelets lose viability rapidly during cold storage (1-6 degC used for RBC storage) -> stored blood contains mostly non-functional, degenerated WBCs/platelets.", None),
("In case of extreme emergency, 'O' Rh negative blood should be transfused- justify.",
 "O group RBCs lack A/B antigens and Rh-negative lacks the D antigen -> the \"universal donor\" - minimal risk of an acute hemolytic reaction when there's no time to cross-match.", None),
("ABO incompatibilities rarely produce hemolytic disease of newborn- Explain.",
 "Naturally occurring anti-A/anti-B antibodies are mostly IgM (don't cross the placenta), and A/B antigens are weakly expressed on fetal RBCs and diluted across other tissues -> much milder disease than Rh incompatibility (IgG, crosses placenta).", None),
]))

# ---------------------------------------------------------------------------
# BUILD PDF
# ---------------------------------------------------------------------------

doc = SimpleDocTemplate("/tmp/workspace/physio-reasoning-qa/Physiology_Reasoning_Questions_3Marks.pdf",
                         pagesize=A4,
                         topMargin=1.4*cm, bottomMargin=1.4*cm,
                         leftMargin=1.6*cm, rightMargin=1.6*cm)

flow = []
flow.append(P("PHYSIOLOGY REASONING QUESTIONS - 3 MARK ANSWERS", title_style))
flow.append(P("Shortest exam-oriented answers | <b>Highlighted line = key point examiner looks for</b>", subtitle_style))

total_q = sum(len(v) for _, v in DATA)
flow.append(P("Total Questions Covered: %d  |  Systems: Renal, Cardiovascular, Respiratory, GIT, General Physiology, Blood" % total_q, subtitle_style))
flow.append(Spacer(1, 6))

for i, (system, qs) in enumerate(DATA):
    if i > 0:
        flow.append(PageBreak())
    flow.append(P(system, section_style))
    for qno, (q, key, note) in enumerate(qs, 1):
        block = [P("Q%d. %s" % (qno, q), q_style), P(key, a_style)]
        if note:
            block.append(P(note, sup_style))
        else:
            block.append(Spacer(1, 4))
        flow.append(KeepTogether(block))

doc.build(flow)
print("PDF built successfully")