Give answer

Reading File

Running Command

cd "/tmp/workspace/attachments/5a0687cc-65f8-4d97-be67-1f142c54acfe/" && python3 -c " import pdfplumber with pdfplumber.open('PATHOPHYSIOLOGY_EXAM (1).pdf') as pdf: print(f'Total pages: {len(pdf.pages)}') for i, page in enumerate(pdf.pages): text = page.extract_text() print(f'--- PAGE {i+1} ---') print(text) print() "

Asking for Preferences

Reading File

Given the budget constraints (107 questions across many topics), I'll provide concise, accurate answers to all questions from my medical knowledge base. Here are the answers:

PATHOPHYSIOLOGY EXAM - Complete Answers

Q1. Subject and content of pathophysiology

Pathophysiology studies the mechanisms of disease - how normal physiology is disrupted to produce signs and symptoms. It bridges basic sciences (anatomy, biochemistry, physiology) and clinical medicine. Clinical pathophysiology applies these mechanisms directly to patient care - explaining why a patient has edema, fever, or shock. It is essential for rational diagnosis and therapy.

Q2. Modeling as the main method of pathophysiology

Types of models:

In vivo - animal experiments (most realistic but ethical constraints)
In vitro - cell/tissue cultures, organ bath preparations
Mathematical/computer - simulations of physiological processes
Clinical - observations in human patients

Principles of experiment design: hypothesis → controls → reproducibility → statistical analysis. Limitations: Animal models may not fully replicate human disease; in vitro lacks systemic context.

Q3. Basic concepts of general nosology

Norm: Range of biological parameters compatible with health and full function
Health: State of complete physical, mental, and social well-being (WHO)
Pre-disease (predisease): State where compensatory mechanisms are strained but disease has not yet manifested; borderline state
Disease: Disruption of normal function in response to damaging factors, with disturbance of adaptation
Pathologic reaction: Short-term, non-adaptive response to a stimulus (e.g., vasospasm from cold)
Pathologic process: A combination of damage and protective responses (e.g., inflammation)
Pathologic state: Stable, persistent result of a pathologic process (e.g., scar tissue)

Q4. Forms of occurrence, course, and outcomes of disease

Forms of occurrence: sudden (acute), gradual (chronic onset). Course: acute (<2 months), subacute (2-6 months), chronic (>6 months); may be continuous or relapsing-remitting. Outcomes: complete recovery, incomplete recovery (defect), transition to chronic form, death. Mechanisms of recovery:

Urgent (emergency): immediate compensatory reactions (tachycardia, vasoconstriction)
Delayed: structural reorganization (hypertrophy, regeneration)
Complete: restoration of normal function and structure

Q5. Terminal states

Terminal states are reversible or irreversible conditions between life and death:

Predagonia: Impaired consciousness, falling BP, irregular breathing
Agonal state: Gasping, chaotic heart activity, loss of consciousness
Clinical death: Cessation of heartbeat and breathing, but cells still viable (4-6 min at normal temperature)
Biological death: Irreversible cessation of all cellular activity; brain death occurs first (cortex within 4-6 min, brainstem later)

Q6. Pathophysiologic bases of resuscitation

Resuscitation must begin within 4-6 minutes of clinical death to prevent irreversible brain damage. Steps: ABC - Airway, Breathing (mouth-to-mouth), Circulation (chest compressions 30:2 ratio). Benefit: Restores perfusion to vital organs. Post-resuscitation disease: Complex of pathological changes after successful resuscitation - reperfusion injury, cerebral edema, multi-organ dysfunction, disseminated intravascular coagulation (DIC). Requires intensive monitoring and support.

Q7. Etiology

Etiology = the study of causes and conditions of disease. Causative factor: The main factor that initiates disease (necessary but may not be sufficient alone). Classification of causative factors:

Exogenous: Physical (trauma, radiation, temperature), chemical (toxins, drugs), biological (bacteria, viruses), social/psychological
Endogenous: Genetic defects, constitutional disorders, metabolic disturbances

Role: The causative factor triggers the disease, determines its specificity, and influences the course and outcome. Identifying it enables causal (etiotropic) treatment.

Q8. Conditions

Conditions modify the likelihood of disease developing but are not the direct cause. Classification:

Favorable (predisposing): increase susceptibility (malnutrition, stress, genetic predisposition, age)
Unfavorable: environmental factors, social conditions
Internal/external

Role: Without proper conditions, even a causative factor may not cause disease (e.g., Mycobacterium tuberculosis requires immune compromise). Critical for prevention strategies.

Q9. Mechanical trauma and traumatic shock

Immediate consequences: hemorrhage, fracture, laceration, nerve damage, pneumothorax. Distant consequences: fat embolism, sepsis, osteomyelitis, PTSD.

Pathogenesis of traumatic shock:

Erective phase: Excitation, normal/elevated BP, tachycardia
Torpid phase: Depression, hypotension, weak pulse, pale cold skin, oliguria

Mechanism: massive pain stimuli → sympathoadrenal activation → vasoconstriction → tissue hypoperfusion → metabolic acidosis → multi-organ failure

Therapy principles: Stop bleeding, analgesia, IV fluids, vasopressors if needed.

Crush syndrome (Bywaters syndrome): Prolonged compression of muscle → rhabdomyolysis → myoglobinuria → acute renal failure on reperfusion.

Q10. High temperature effects

Burns: Local coagulative necrosis. Severity by depth (I-IV degree) and body surface area affected (rule of nines). Burn disease: Systemic response to large burns:

Burn shock (first 48h) - hypovolemia, pain
Toxemia - absorption of burn toxins
Septicotoxemia - infection
Recovery

Hyperthermia: Core temperature rise due to overwhelmed heat-loss mechanisms. Causes: hot environment, excessive clothing, anticholinergics. Heat stroke: Life-threatening hyperthermia >40°C; hot dry skin, confusion, delirium; pathogenesis: hypothalamic failure, cerebral edema, cardiovascular collapse. Sunstroke: Direct infrared radiation on the head → meningeal/brain vessel dilation, edema.

Q11. Low temperature effects

Hypothermia: Core T <35°C.

Mild (32-35°C): shivering, vasoconstriction, tachycardia
Moderate (28-32°C): loss of shivering, bradycardia, atrial fibrillation
Severe (<28°C): coma, ventricular fibrillation, apnea

Frostbite: Local freezing → ice crystal formation → cell damage, vascular injury → ischemia → gangrene (grades I-IV). Role in colds: Cold causes reflex vasoconstriction of nasal mucosa → reduced local immunity → easier viral entry. Medical use of hypothermia: Cardiosurgery, neuroprotection after cardiac arrest (targeted temperature management 32-36°C).

Q12. Barometric pressure changes

High pressure (hyperbaria):

Nitrogen narcosis at depth
Oxygen toxicity (CNS and pulmonary)
Decompression sickness (bends): rapid ascent → N₂ bubbles form in blood/tissues → joint pain, neurological deficit, chokes (pulmonary emboli)
Prevention: slow ascent; treatment: recompression chamber

Low pressure (hypobaria):

Altitude sickness: hypoxia, pulmonary/cerebral edema, polycythemia
Explosive decompression: barotrauma, gas embolism
Prevention: acclimatization, supplemental oxygen

Q13. Radiation lesions - etiology and pathogenesis

Etiologic factor: Ionizing radiation (alpha, beta, gamma, X-ray, neutrons). Mechanisms:

Direct ionization of DNA, proteins, membranes
Indirect: radiolysis of water → free radicals (OH•, H•) → oxidative damage

Distant consequences: Malignancies (leukemia, solid tumors), cataracts, infertility, premature aging, genetic mutations in offspring.

Chronic radiation sickness:

Caused by prolonged low-dose exposure
Characteristic: gradual immune suppression, hematopoietic failure, CNS dysfunction, increased cancer risk
Stages: functional (reversible), organic (irreversible structural changes)

Q14. Acute Radiation Sickness (ARS)

Dose-dependent forms:

<1 Gy: No acute disease (slight hematologic changes)
1-2 Gy: Mild ARS - bone marrow form (lymphopenia)
2-4 Gy: Moderate ARS
4-6 Gy: Severe ARS
6-10 Gy: Very severe ARS - bone marrow form
10-20 Gy: Intestinal form - GI epithelium destruction, intractable diarrhea, death in 1-2 weeks
>20 Gy: Cerebrovascular form - CNS edema, convulsions, death in hours-days

Pathogenesis of bone marrow form:

Initial reaction (hours): Nausea, vomiting, lymphopenia
Latent period (days-weeks): apparent recovery
Manifest illness: Pancytopenia → hemorrhage, infection, anemia
Recovery or death

Q15. Ultraviolet (UV) radiation

Pathogenic effects:

DNA damage (pyrimidine dimers → mutations → skin cancer)
Protein denaturation in skin → erythema, sunburn
Immunosuppression (Langerhans cell damage)
Cataract formation (UVB)
Photoallergic/phototoxic reactions

Beneficial effects (medical use):

Vitamin D synthesis (UV-B 290-315 nm)
Bactericidal (sterilization of operating rooms)
Treatment of psoriasis, vitiligo, rickets, neonatal jaundice (phototherapy)

Q16. Electric current injury

Factors determining pathogenic effect:

Type (AC more dangerous than DC at same voltage)
Voltage and current intensity
Duration of contact
Path through body (hand-to-hand passes through heart)
Skin resistance (wet skin = lower resistance = greater current)

Mechanisms of damage:

Thermal: Joule heat → burns along current path
Electrolytic: disruption of membrane ion gradients
Mechanical: muscle tetany, fractures, falls
Biological: direct depolarization of nerve/muscle cells

Mechanisms of death:

Ventricular fibrillation (most common with AC)
Respiratory arrest (tetany of respiratory muscles or central apnea)
Brainstem damage

Q17. Poisonings

Definition: Pathological condition caused by exogenous toxic substances (poisons).

Classification of poisons:

By origin: inorganic, organic, biological (plant, animal, microbial)
By mechanism: neurotropic, hepatotropic, nephrotoxic, hemotropic, cytotoxic
By use: industrial, household, agricultural (pesticides), medicinal

Types of poisoning: acute, subacute, chronic; exogenous vs. endogenous.

Factors determining severity: dose, route of entry, solubility, individual reactivity, age, body weight.

Emergency care principles: Remove from exposure, gastric lavage, activated charcoal, specific antidotes (e.g., naloxone for opioids, atropine for organophosphates), supportive care, dialysis if needed.

Q18. Pathogenesis

Pathogenesis = the mechanism of development of disease from initial damage to final manifestation. Types: specific (mechanisms unique to that disease) vs. nonspecific (universal mechanisms).

Damage is the initial link - may occur at:

Molecular level (enzyme inhibition, DNA mutation)
Cellular level (membrane damage, organelle dysfunction)
Tissue level (necrosis, inflammation)
Organ level (functional failure)
Systemic level (shock, multi-organ failure)

Pathogenetic factors: All secondary changes that arise from the initial damage and perpetuate or amplify disease.

Q19. Cause-effect relations in pathogenesis

Cause-effect chains: Initial damage → pathogenetic factor A → factor B → etc. Leading link: The single most critical step in the chain; targeting it breaks the entire pathogenesis (e.g., thrombus formation is the leading link in MI). Vicious circles (circulus vitiosus): When a pathogenetic factor becomes a cause of itself (e.g., heart failure → poor coronary perfusion → worse heart failure).

Universal mechanisms:

Hypoxia, free radical damage, inflammation, immune activation, necrosis, apoptosis

Local vs. general: Local reaction (e.g., wound inflammation) vs. systemic response (fever, SIRS). Specific vs. nonspecific: Specific = unique to disease; nonspecific = common to many (e.g., fever occurs in infection, infarction, malignancy).

Q20. Protective-compensatory processes

Protective reactions: Prevent damage (cough, vomiting, pain withdrawal, fever killing pathogens). Compensatory reactions: Maintain function despite damage (tachycardia in anemia, hypertrophy in pressure overload). Restorative processes: Regeneration, healing, scar formation.

Pathologic reflexes in disease:

Conditioned: learned responses that can exacerbate disease (e.g., angina triggered by stress memory)
Unconditioned: innate reflexes that may worsen pathology (e.g., vasovagal syncope, Bezold-Jarisch reflex in MI)

Q21. Reactivity of the organism

Reactivity = the ability of the organism to respond to stimuli. Types:

Species reactivity (all humans respond to hypoxia)
Group reactivity (age, sex, constitutional differences)
Individual reactivity (personal response)
Specific (immune) vs. nonspecific
Physiological vs. pathological

Factors determining reactivity: Nervous system, endocrine system, immune system, age, sex, genetics, nutrition.

Constitution: Morpho-functional type of organism (Hippocrates: sanguine, choleric, etc.; Kretschmer: asthenic, athletic, pyknic). Resistance: Ability to resist damaging factors. Reactivity shapes resistance but they are not identical (high reactivity may mean either high or low resistance depending on context).

Q22. Human genetic diseases

Genetic disease: Caused by mutations in DNA (inherited or new mutation). Congenital disease: Present at birth - may be genetic OR caused by environmental factors during development (infections, drugs, radiation). Phenocopy: Environmentally caused condition that mimics a genetic disease (e.g., fetal alcohol syndrome mimicking chromosomal abnormalities).

Classification of genetic diseases:

Gene (monogenic): single gene mutation - autosomal dominant/recessive, X-linked
Chromosomal: numerical or structural chromosome abnormalities
Multifactorial (polygenic): multiple genes + environment

Q23. Etiology and pathogenesis of genetic diseases

Molecular (gene) diseases:

Autosomal recessive: Phenylketonuria (PAH mutation → phenylalanine accumulation → brain damage), cystic fibrosis (CFTR → thick secretions), sickle cell anemia (HbS)
Autosomal dominant: Marfan syndrome (FBN1), Huntington's disease (HTT triplet repeat)
X-linked: Hemophilia A (F8), Duchenne muscular dystrophy (dystrophin)

Chromosomal diseases:

Trisomy 21 (Down syndrome): intellectual disability, flat facies, epicanthal folds, cardiac defects
Trisomy 18 (Edwards), Trisomy 13 (Patau)
Turner syndrome (45,X): short stature, gonadal dysgenesis
Klinefelter syndrome (47,XXY): male hypogonadism, gynecomastia

Q24. Diagnosis, therapy, and prevention of genetic diseases

Diagnosis:

Karyotyping (chromosomal analysis)
Molecular methods: PCR, FISH, whole-genome sequencing
Biochemical screening (newborn screening for PKU, hypothyroidism)
Prenatal: amniocentesis, chorionic villus sampling (CVS), ultrasound

Therapy:

Substrate restriction (PKU: low-phenylalanine diet)
Enzyme replacement therapy (Gaucher disease)
Gene therapy (experimental)
Symptomatic management

Prevention:

Genetic counseling
Carrier screening
Preimplantation genetic diagnosis (IVD)
Prenatal screening and selective termination

Q25. Immunodeficiencies

Definition: Inability of the immune system to mount an adequate response to pathogens. Types:

Primary (congenital): Inherited defects
- B-cell: X-linked agammaglobulinemia (Bruton) → recurrent bacterial infections
- T-cell: DiGeorge syndrome → recurrent viral/fungal infections
- Combined: SCID (severe combined immunodeficiency)
- Phagocyte: Chronic granulomatous disease
- Complement: C1q deficiency → SLE-like
Secondary (acquired): HIV/AIDS, malnutrition, chemotherapy, splenectomy, diabetes

Manifestations: Recurrent severe infections with unusual organisms, failure to thrive, autoimmunity, increased cancer risk.

Q26. Allergy: classification

Allergy = exaggerated, harmful immune response to normally harmless antigens (allergens).

Cooke classification (by onset):

Immediate hypersensitivity: reaction within minutes (IgE-mediated)
Delayed hypersensitivity: reaction after 24-72 hours (T-cell mediated)

Gell & Coombs classification:

Type I (anaphylactic/IgE-mediated): asthma, urticaria, anaphylaxis
Type II (cytotoxic): autoimmune hemolytic anemia, transfusion reactions
Type III (immune complex): serum sickness, SLE, post-streptococcal GN
Type IV (delayed/cell-mediated): contact dermatitis, TB skin test, graft rejection

Q27. Allergens and pathogenesis

Allergens: Antigens that trigger allergic reactions.

Exogenous: Inhaled (pollen, dust mites, mold), ingested (food), contact (latex, nickel), injected (drugs, venom)
Endogenous (autoantigens): Modified self proteins

Pathogenesis of Type I (immediate):

Sensitization: First exposure → B cells produce IgE → IgE binds to mast cells/basophils
Re-exposure: Allergen cross-links IgE → mast cell degranulation
Mediators released: Histamine, tryptase, leukotrienes (LTC4, LTD4), prostaglandins, PAF
Early phase: Vasodilation, bronchoconstriction, mucus (within minutes)
Late phase: Eosinophil/neutrophil infiltration (4-8h later)

Pathogenesis of Type IV (delayed):

Sensitization: Antigen presented by APCs to T-helper 1 cells
Re-exposure: TH1 cells release IFN-γ → macrophage activation → tissue damage
No antibody involvement; takes 24-72 hours

Q28. Atopic diseases

Atopy: Genetic predisposition to produce elevated IgE and develop Type I hypersensitivity. Causes: Genetic (FcεRI, IL-4, IL-13 gene variants) + environmental triggers; "hygiene hypothesis" - reduced early childhood microbial exposure → TH2 bias.

Diseases:

Atopic dermatitis (eczema): Pruritic, eczematous rash; impaired skin barrier (filaggrin mutation), IgE elevation
Allergic rhinitis: Sneezing, watery discharge, nasal congestion; triggered by inhaled allergens
Allergic asthma: Bronchoconstriction, wheezing, reversible airflow obstruction
Food allergy: GI symptoms, urticaria, anaphylaxis to foods

Q29. Anaphylaxis

Anaphylaxis = severe, life-threatening systemic allergic reaction. Types:

True anaphylaxis (immunologic): IgE-mediated (penicillin, bee venom, peanuts)
Anaphylactoid reaction: Clinically identical but not IgE-mediated; direct mast cell activation (contrast media, aspirin, opioids)

Experimental reproduction: Portier & Richet (1902) - sensitized dogs with sea anemone toxin, re-exposure caused fatal reaction → coined "anaphylaxis" (opposite of prophylaxis). Active anaphylaxis: repeated immunization in guinea pigs. Passive anaphylaxis: transfer of immune serum to naïve animal.

Q30. Anaphylactic shock

Causes: Drugs (penicillin, NSAIDs), foods (peanuts, shellfish), insect venom, latex, blood products.

Mechanism:

IgE-mediated massive mast cell/basophil degranulation
Histamine → profound vasodilation → distributive shock
Increased vascular permeability → angioedema, intravascular volume loss
Bronchoconstriction → respiratory failure
Decreased cardiac output → multi-organ hypoperfusion

Manifestations: Urticaria, angioedema, bronchospasm, hypotension, tachycardia, GI symptoms, loss of consciousness.

Emergency care:

Epinephrine (adrenaline) IM 0.3-0.5 mg (first-line - α1 vasoconstriction, β2 bronchodilation)
Supine position, O₂
IV fluids (crystalloids)
Antihistamines (H1 + H2 blockers)
Corticosteroids (prevent late phase)
Glucagon if on beta-blockers

Q31. Diagnostics and hyposensitization in allergy

Diagnostic methods:

Skin prick/scratch tests (immediate hypersensitivity)
Intradermal tests
Patch tests (Type IV, contact dermatitis)
Serum total and specific IgE (RAST/ImmunoCAP)
Provocation tests (bronchial, nasal, oral)
Elimination diet

Hyposensitization (allergen immunotherapy):

Specific: Subcutaneous or sublingual administration of increasing allergen doses → shift from TH2 to TH1 response, induction of regulatory T cells, IgG4 "blocking" antibodies
Nonspecific: Antihistamines, corticosteroids, mast cell stabilizers (cromolyn), omalizumab (anti-IgE)

Q32. Serum sickness

Etiology: Administration of heterologous serum (horse antitoxins) or drugs (penicillin, sulfonamides). Pathogenesis (Type III):

Antigen excess → soluble immune complexes form in blood
Complexes deposit in vessel walls, glomeruli, joints, skin
Complement activation → C3a, C5a (anaphylatoxins) → neutrophil recruitment → tissue damage

Types: Acute (7-10 days after first exposure) or accelerated (2-4 days with prior sensitization). Manifestations: Fever, arthralgia, urticaria/rash, lymphadenopathy, proteinuria, glomerulonephritis.

Q33. Contact dermatitis, graft rejection, bacterial allergy, Hashimoto's, Graves' disease

Contact dermatitis (Type IV):

Allergens: nickel, chromium, poison ivy (urushiol), latex, cosmetics
Sensitization → T-cell mediated → vesicular eczematous rash at contact site

Graft rejection (Type IV + antibody-mediated):

Hyperacute (<24h): preformed antibodies → thrombotic occlusion
Acute (days-weeks): CTL attack of donor MHC
Chronic (months-years): fibrosis, vasculopathy

Bacterial allergy (Type IV): Tuberculin reaction, lepromin test - TH1 cells attack mycobacterial antigens.

Hashimoto's thyroiditis (autoimmune, Type IV/II): Anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin antibodies + cytotoxic T cells → thyroid destruction → hypothyroidism.

Diffuse toxic goiter (Graves' disease, Type V/II): TSH-receptor stimulating antibodies (TRAb) → constant thyroid activation → hyperthyroidism, goiter, exophthalmos.

Q34. Autoallergy (autoimmunity)

Autoallergy: Immune response against self-antigens causing tissue damage.

Causes/Mechanisms:

Molecular mimicry: Pathogen antigen similar to self-antigen (e.g., streptococcal M protein → cardiac antigens in rheumatic fever)
Bystander activation: Inflammatory cytokines activate autoreactive cells
Sequestered antigen release: Myelin, lens protein, sperm (normally hidden) exposed by trauma/infection
Epitope spreading: Immune response broadens beyond initial antigen
Loss of tolerance: Regulatory T cell failure

Examples: SLE (anti-dsDNA), rheumatoid arthritis (RF, anti-CCP), MS (myelin antigens), type 1 diabetes (islet cells), pemphigus vulgaris (desmosome proteins).

Q35. Drug allergy

Causes: Most drugs are haptens - small molecules that conjugate to proteins to become full antigens. True drug antigens are large molecules (insulin, monoclonal antibodies).

Mechanisms:

Type I: penicillin anaphylaxis, aspirin-induced urticaria
Type II: drug-induced hemolytic anemia (methyldopa), thrombocytopenia (quinine)
Type III: serum sickness-like (sulfonamides)
Type IV: contact dermatitis, DRESS syndrome, SJS/TEN

Manifestations:

Skin: urticaria, maculopapular rash, erythema multiforme, Stevens-Johnson syndrome (SJS), DRESS
Systemic: anaphylaxis, drug fever, lupus-like syndrome, hepatitis, nephritis

Q36. Microcirculation disorders

Typical forms:

Arteriolar spasm: Reduced blood flow, pale cold tissue
Arterial hyperemia: Increased blood flow, redness, warmth
Venous hyperemia (congestion): Sluggish outflow, cyanosis, edema
Stasis: Cessation of blood flow

Intravascular factors: Increased blood viscosity, altered cell deformability, aggregation. Extravascular factors: Compression of vessels by edema/tumor.

Sludge phenomenon: Reversible aggregation of erythrocytes in capillaries without hemolysis.

Types: classical (coin-stack formation), granular (small aggregates), amorphous
Mechanisms: infection, DIC, shock, burns → release of proaggregating factors (fibrinogen, globulins)

Q37. Peripheral circulation disorders

Ischemia: Insufficient arterial blood supply.

Causes: thrombosis, embolism, vasospasm, atherosclerosis, compression
Manifestations: pallor, pain, reduced temperature, functional loss, necrosis if prolonged

Arterial hyperemia: Increased arterial inflow.

Physiological (functional: exercise, emotion) or pathological (inflammatory, collateral)
Manifestations: redness, warmth, pulsation, increased function

Venous hyperemia (passive congestion):

Causes: heart failure, venous obstruction (thrombosis, compression)
Manifestations: cyanosis, edema, cold skin, stasis, trophic changes

Stasis: Complete cessation; leads to ischemic necrosis if prolonged.

Q38. Thrombosis

Virchow's triad:

Vascular wall injury (endothelial damage → collagen exposure → platelet adhesion)
Slowed blood flow (stasis → clot accumulation)
Hypercoagulability (inherited thrombophilia, pregnancy, malignancy)

Mechanism: Platelet adhesion (vWF/collagen) → activation → aggregation (fibrinogen/GPIIb/IIIa) → thrombin generation → fibrin net = stable thrombus.

Outcomes: Aseptic lysis (fibrinolysis), organization (replaced by fibrous tissue), recanalization, calcification (phlebolith), septic thrombosis.

Significance: DVT, pulmonary embolism, stroke, MI - major causes of morbidity/mortality.

Q39. DIC Syndrome

DIC (Disseminated Intravascular Coagulation): Systemic activation of coagulation → microthrombi throughout microcirculation → consumption of clotting factors and platelets → paradoxical bleeding.

Causes: Sepsis (most common), obstetric complications (placental abruption, amniotic fluid embolism), trauma, malignancy, transfusion reactions, burns.

Stages:

Hypercoagulation: Microthrombi, organ ischemia
Transition: Mixed picture
Hypocoagulation/fibrinolysis: Bleeding from all sites, factor depletion

Manifestations: Purpura, petechiae, oozing from IV sites, organ failure (renal, hepatic, pulmonary - "shock organs"), thrombocytopenia, prolonged PT/aPTT, low fibrinogen, elevated D-dimers, schistocytes.

Q40. Embolism

Embolism: Obstruction of a vessel by material (embolus) carried in the bloodstream.

Classification:

By origin: thrombus (most common), fat, air/gas, tumor cells, amniotic fluid, parasites
By direction: orthograde (with flow), retrograde (against flow), paradoxical (via patent foramen ovale)

Pulmonary embolism (from venous thrombus): Obstruction of pulmonary arteries → right heart strain, ventilation-perfusion mismatch, hypoxemia, pulmonary infarction (if large vessel).

Systemic embolism (large circle): Stroke, mesenteric ischemia, limb ischemia - from left heart thrombus, AF, endocarditis.

Portal vein embolism: Hepatomegaly, portal hypertension, ascites, esophageal varices.

Q41. Inflammation

Inflammation: Protective vascular-mesenchymal response to local tissue damage or pathogens, aimed at eliminating the cause and restoring tissue integrity.

Etiology: Physical (trauma, heat), chemical (acids, toxins), biological (bacteria, viruses, fungi), immune.

Local signs (Celsus): Rubor (redness), calor (heat), tumor (swelling), dolor (pain) + functio laesa (loss of function).

General signs: Fever, leukocytosis, elevated ESR/CRP, malaise.

Pathogenesis: Damage → mediator release → vascular changes → exudation → leukocyte emigration → phagocytosis → resolution.

Biological significance: Defense against infection, initiates repair; but can cause damage if excessive (autoimmune disease, chronic inflammation).

Therapy principle: Target underlying cause + modulate excessive response (NSAIDs, corticosteroids).

Q42. Alteration and mediators of inflammation

Alteration: Primary (direct damage by causative agent) + Secondary (from mediators and hypoxia).

Key inflammatory mediators:

Cell-derived: Histamine (mast cells), serotonin (platelets), prostaglandins (via COX), leukotrienes (via LOX), PAF, cytokines (IL-1, IL-6, TNF-α), NO
Plasma-derived: Complement (C3a, C5a), kinins (bradykinin via Hageman factor), coagulation factors

Vascular reactions: Transient arteriolar constriction → sustained vasodilation (Lewis triple response) → increased permeability → edema.

Metabolic changes: Increased glycolysis → lactic acid → local acidosis. Lipolysis, proteolysis in tissue.

Physical-chemical changes: Decreased pH, increased osmolarity, increased oncotic pressure in interstitium → promotes exudation.

Q43. Exudation, emigration, phagocytosis, and proliferation

Exudation: Fluid + proteins leave vessels into tissue.

Mechanism: increased hydrostatic pressure + increased permeability → protein-rich exudate

Emigration: Leukocytes leave capillaries.

Margination and rolling (selectins)
Adhesion (integrins/ICAM)
Transmigration/diapedesis (CD31/PECAM)
Chemotaxis toward inflammation focus (C5a, IL-8, LTB4)

Phagocytosis:

Chemotaxis → recognition (opsonization by IgG, C3b)
Engulfment (pseudopod extension)
Phagosome formation → fusion with lysosome (phagolysosome)
Killing: oxidative burst (NADPH oxidase → O₂•⁻, H₂O₂, HOCl) + lysozyme, defensins

Proliferation: Fibroblast activation → collagen synthesis → granulation tissue → scar (regeneration if labile/stable cells; fibrosis if permanent cells).

Q44. Chronic inflammation

Definition: Prolonged inflammation (weeks-months-years) in which active inflammation, tissue injury, and attempts at repair proceed simultaneously.

Types:

Primary chronic (from onset): TB, leprosy, Crohn's disease
Secondary chronic: unresolved acute inflammation

Causes: Persistent infection (H. pylori, TB), autoimmune disease, foreign body, repeated injury.

Mechanisms: Macrophage activation (M1 pro-inflammatory) → granuloma formation in granulomatous diseases. TH1-dominated response.

Features vs. acute inflammation:

Dominated by mononuclear cells (macrophages, lymphocytes, plasma cells) vs. neutrophils
Fibrosis and tissue destruction prominent
Granuloma formation
Less vascular reactivity

Q45. Fever: etiology and pathogenesis

Fever: Controlled increase in body temperature set-point mediated by the hypothalamus.

Etiology:

Infectious: bacterial (endotoxin/LPS), viral, fungal, parasitic
Noninfectious: tissue necrosis (MI, PE), malignancy, autoimmune, drugs

Pathogenesis:

Exogenous pyrogens (LPS, viral RNA) activate macrophages
Endogenous pyrogens released: IL-1β, IL-6, TNF-α, IFN-γ
Endogenous pyrogens act on hypothalamic anterior area → PGE₂ synthesis (via COX-2)
PGE₂ raises the thermoregulatory set-point
Peripheral vasoconstriction + shivering → heat conservation/generation → temperature rises

Q46. Stages of fever and organ effects

Stages:

Stadium incrementi (rise): Chills, shivering, vasoconstriction, pallor, horripilation
Stadium acme (peak): Hot, flushed skin, headache, delirium at very high T
Stadium decrementi (fall): Sweating, vasodilation, diuresis; lytic (gradual) or crisis (sudden)

Organ effects by stage:

System	Stage 1	Stage 2	Stage 3
CVS	Tachycardia (+10 BPM per 1°C), ↑BP	Tachycardia, vasodilation	↓BP if crisis
Nervous	Chills	Confusion, febrile seizures	Return to normal
Renal	↓urine output	Oliguria, dark urine	Diuresis
Digestive	↓appetite	Dry mouth, constipation	Improved
Immune	Activation	Peak activation	Subsides
Metabolism	↑catabolism	↑BMR (+13% per 1°C)	Normalizes

Q47. Temperature curves and significance of fever

Types of fever curves:

Continuous (febris continua): Daily variation <1°C; lobar pneumonia, typhoid
Remittent (febris remittens): Daily variation >1°C but T doesn't normalize; most infections
Intermittent (febris intermittens): T falls to normal each day; malaria (tertian, quartan)
Hectic/Septic: Wide swings >3°C; abscess, sepsis
Relapsing: Days of fever alternating with normal; Borrelia, Hodgkin's lymphoma
Undulant: Gradual rise and fall over days; brucellosis

Biological significance of fever:

Inhibits microbial growth (many organisms temperature-sensitive)
Enhances immune function (increased phagocyte activity, NK cells, T-cell proliferation)
Increases production of heat-shock proteins (cytoprotective)

Distinction from overheating (hyperthermia): Fever = elevated set-point (pyrogens); hyperthermia = set-point normal but heat-dissipation overwhelmed.

Antipyretic rationale: NSAIDs/paracetamol inhibit COX → block PGE₂ synthesis. Pyrotherapy: Artificial fever induction (malaria therapy for neurosyphilis - Wagner-Jauregg).

Q48. Tumor growth characteristics

Tumor growth: Autonomous, uncontrolled proliferation of cells that escapes normal growth regulation. Tumor: Mass of abnormal cells showing atypism and autonomous growth. Tumor progression: Gradual acquisition of increasingly malignant features over time (Nowell's clonal evolution).

Tumor atypism (types):

Morphological: Cellular (pleomorphism, hyperchromatism, increased N:C ratio, abnormal mitoses) and tissue (loss of normal architecture)
Biochemical: Altered enzyme pattern, production of ectopic hormones, glycolysis predominance (Warburg effect)
Functional: Loss of specialized functions
Antigenic: Expression of tumor-specific/associated antigens
Metabolic: Anaerobic glycolysis even in O₂ presence

Oncomarkers: Substances produced by tumor or in response to tumor, detectable in blood:

AFP (hepatocellular carcinoma, testicular)
CEA (colorectal, lung)
PSA (prostate)
CA-125 (ovarian)
CA 19-9 (pancreatic)
β-hCG (choriocarcinoma)

Q49. Etiology of tumors

Types of carcinogenic factors:

Chemical carcinogens:
- Direct-acting: nitrogen mustards, alkylating agents
- Indirect (procarcinogens activated by cytochrome P450): polycyclic aromatic hydrocarbons (benzo[a]pyrene), aflatoxin B1, aromatic amines, nitrosamines
Physical carcinogens:
- Ionizing radiation (UV → skin; X-ray, gamma → leukemia, thyroid, breast)
- Chronic mechanical irritation
Biological carcinogens (oncogenic viruses):
- DNA viruses: HPV (cervical cancer, oropharyngeal), EBV (Burkitt's lymphoma, nasopharyngeal carcinoma), HBV/HCV (hepatocellular carcinoma)
- RNA viruses (retroviruses): HTLV-1 (adult T-cell leukemia)
- H. pylori (gastric cancer, MALT lymphoma)

Concepts:

Procarcinogen: Requires metabolic activation to become carcinogenic
Cocarcinogen: Not carcinogenic alone but enhances the effect of a carcinogen (e.g., phorbol esters, alcohol)
Syncarcinogen: Two carcinogens acting together with synergistic effect (smoking + asbestos → dramatically increases lung cancer risk)

Q50. Pathogenesis of tumors: molecular mechanisms and stages

Molecular mechanisms of carcinogenesis:

Proto-oncogene activation → oncogene: Gene mutation, amplification, translocation → constitutive growth signals (RAS, MYC, HER2)
Tumor suppressor gene inactivation (two-hit hypothesis - Knudson): TP53, RB1, BRCA1/2 - need both alleles lost
DNA repair gene inactivation: MLH1, MSH2 (mismatch repair) → microsatellite instability
Telomerase reactivation: Bypasses replicative senescence → immortalization
Epigenetic changes: Promoter hypermethylation silencing tumor suppressors

Stages of carcinogenesis:

Initiation: Irreversible DNA mutation (carcinogen-induced or spontaneous)
Promotion: Clonal expansion of initiated cells by promoting agents (not mutagenic alone); reversible
Progression: Acquisition of increasingly malignant phenotype (invasion, metastasis)

Role of organism reactivity: Immunocompromised patients have higher cancer risk; tumor microenvironment shapes growth.

Q51. Antiblastome resistance

Antiblastome resistance: The ability of the organism to resist tumor development and growth.

Mechanisms:

Immunological:
- CTL (CD8+ T cells) recognize and kill tumor cells via MHC I/tumor antigen
- NK cells kill MHC I-negative tumor cells
- Macrophage tumoricidal activity
- Antibody-dependent cellular cytotoxicity (ADCC)
- Tumor immunoediting: elimination → equilibrium → escape
Non-immunological:
- Contact inhibition (tumor cells lose this)
- Apoptosis (tumor cells evade via Bcl-2 overexpression)
- Antioxidant systems
- DNA repair mechanisms

Q52. Tumor-organism interaction, metastasis, cachexia

Tumor effects on organism:

Local: compression, obstruction, hemorrhage, ulceration
Systemic: cachexia, paraneoplastic syndromes, immune suppression, hypercoagulability

Organism effects on tumor: Immune surveillance (eliminates early transformed cells), hormonal environment, nutritional status.

Metastasis - stages:

Local invasion (degradation of basement membrane by MMPs)
Intravasation (entry into blood/lymphatic vessels)
Survival in circulation
Arrest at distant site
Extravasation
Formation of secondary tumor (requires angiogenesis)

Routes: Lymphatic (carcinomas), hematogenous (sarcomas, also carcinomas), transcoelemic (peritoneal spread).

Cachexia: Extreme wasting; mechanisms:

TNF-α/IL-6/IL-1 → anorexia (suppress appetite), increased catabolism
Tumor competes for nutrients
Increased resting energy expenditure (Warburg glycolysis inefficiency)
Proteolysis-inducing factor (PIF) from tumor

Prevention/therapy principles: Surgery, radiation, chemotherapy, immunotherapy (checkpoint inhibitors), targeted therapy (imatinib), hormone therapy, supportive care.

Q53. Diabetes mellitus

Diabetes mellitus: Chronic metabolic disorder characterized by hyperglycemia due to insulin deficiency, resistance, or both.

Type 1 DM:

Autoimmune destruction of pancreatic β-cells (T-cell mediated, anti-GAD/anti-islet antibodies)
Absolute insulin deficiency
Young, lean patients; acute onset; ketosis-prone
Genetic: HLA-DR3, DR4 associations

Type 2 DM:

Initially: peripheral insulin resistance (in muscle, fat, liver)
β-cells compensate with hyperinsulinemia → eventual β-cell exhaustion
Risk factors: obesity (especially visceral), physical inactivity, genetic predisposition
Pathogenesis: lipotoxicity, glucotoxicity, mitochondrial dysfunction, amyloid deposits (IAPP) in islets

Q54. Metabolic disorders in diabetes mellitus

Carbohydrate metabolism: Glucose cannot enter cells adequately → hyperglycemia → glycosuria (when exceeds renal threshold ~10 mmol/L) → osmotic diuresis → polyuria, polydipsia, polyphagia.

Fat metabolism: Increased lipolysis → elevated free fatty acids → hepatic ketogenesis (acetoacetate, β-hydroxybutyrate, acetone) → ketoacidosis (especially T1DM) → metabolic acidosis + ketonuria.

Protein metabolism: Increased protein catabolism → negative nitrogen balance, muscle wasting, impaired wound healing.

Organ effects:

Kidney: microalbuminuria → proteinuria (glomerulosclerosis - Kimmelstiel-Wilson lesion)
Eyes: retinal microaneurysms → hemorrhages → neovascularization
Nerves: axonal degeneration and demyelination
Liver: fatty liver, glycogen accumulation

Q55. Complications of diabetes mellitus

Angiopathies:

Microangiopathy: Basement membrane thickening → retinopathy, nephropathy, neuropathy; mechanism: sorbitol accumulation (polyol pathway), glycation of proteins (AGEs), PKC activation
Macroangiopathy: Accelerated atherosclerosis → MI, stroke, peripheral arterial disease

Neuropathies:

Peripheral: distal symmetric polyneuropathy (glove-stocking sensory loss), mononeuropathy, autonomic neuropathy (gastroparesis, postural hypotension, impotence)
Mechanism: sorbitol in Schwann cells → osmotic damage, ischemia from vasa nervorum disease

Diabetic comas:

Diabetic ketoacidosis (DKA): T1DM; low insulin → ketogenesis → anion-gap metabolic acidosis; Kussmaul breathing, fruity breath; treatment: insulin, IV fluids, K+
Hyperosmolar hyperglycemic state (HHS): T2DM; extreme hyperglycemia >33 mmol/L, severe dehydration, no ketosis; treatment: fluids + insulin
Hypoglycemic coma: Excess insulin; treat with glucose IV or glucagon IM

Q56. Nitrogen balance and protein metabolism disorders

Positive nitrogen balance: N intake > N loss; seen in growth, pregnancy, recovery after illness, anabolic states. Negative nitrogen balance: N loss > N intake; seen in starvation, severe infection, burns, malignancy, Cushing's syndrome.

Disorders of protein assimilation:

Reduced digestion: pancreatic exocrine insufficiency (↓proteases)
Reduced absorption: celiac disease, IBD

Disorders of tissue metabolism:

Increased catabolism: cortisol excess, sepsis, immobilization
Impaired synthesis: liver failure

Plasma protein disorders:

Hypoalbuminemia: liver disease, nephrotic syndrome, malnutrition → edema
Dysproteinemia: increased globulins in chronic infection/inflammation, M-protein in myeloma
Acute phase proteins: CRP, fibrinogen, ferritin ↑ in inflammation

Q57. Lipid metabolism disorders and obesity

General causes of lipid disorders: Genetic (familial hypercholesterolemia - LDL receptor mutation), dietary, endocrine (hypothyroidism, Cushing's, DM), renal disease (nephrotic syndrome).

Obesity: BMI >30 kg/m².

Exogenous (nutritional): caloric intake > expenditure; most common
Endocrine: Hypothyroidism, Cushing's syndrome, hypogonadism, polycystic ovary syndrome
Hypothalamic: Craniopharyngioma, trauma to satiety center

Pathogenesis: Excess energy → triglyceride storage in adipocytes → adipokine imbalance (↑leptin but leptin resistance, ↓adiponectin) → insulin resistance → metabolic syndrome.

Significance: Increased risk of T2DM, hypertension, dyslipidemia, cardiovascular disease, NAFLD, sleep apnea, certain cancers, osteoarthritis.

Treatment: Caloric restriction, exercise, behavioral therapy; pharmacotherapy (orlistat, GLP-1 agonists); bariatric surgery for severe obesity.

Q58. Atherosclerosis

Phospholipid metabolism disorders: Sphingomyelin accumulation (Niemann-Pick disease); phospholipidosis from drug toxicity.

Cholesterol metabolism disorders: Elevated LDL → xanthomas, xanthelasmas, corneal arcus, atherosclerosis.

Atherosclerosis - pathogenesis (response to injury theory):

Endothelial injury (hypertension, smoking, hyperglycemia, LDL)
LDL enters intima → oxidized LDL (oxLDL)
Monocyte adhesion and infiltration → macrophages
Macrophages engulf oxLDL via scavenger receptors → foam cells
Smooth muscle cell migration from media → proliferation
Extracellular lipid pool + foam cells + SMCs + fibrous cap = atherosclerotic plaque
Plaque rupture → thrombus → acute coronary syndrome/stroke

Prevention: Lipid lowering (statins), BP control, smoking cessation, exercise, diet. Treatment: Statins, PCSK9 inhibitors, aspirin, percutaneous coronary intervention/CABG.

Q59. Hypohydration

Hypohydration (dehydration): Negative water balance; total body water deficit.

Types:

Isotonic (isoosmolar): Loss of equal water and electrolytes (diarrhea, vomiting, bleeding); plasma osmolality normal; intracellular volume preserved
Hypotonic (hyposmolar): Na loss > water loss (diuretics, Addison's); low plasma osmolality; water shifts into cells → cellular swelling
Hypertonic (hyperosmolar): Water loss > Na loss (fever, hyperventilation, diabetes insipidus); high plasma osmolality; water shifts out of cells → cellular shrinkage, intense thirst

Manifestations: Thirst, decreased skin turgor, dry mucous membranes, oliguria, tachycardia, hypotension, confusion (severe).

Correction: Replace fluid + electrolytes based on type (isotonic saline for isotonic dehydration; free water for hypertonic; careful Na replacement for hypotonic).

Q60. Hyperhydration, edema, and dropsy

Hyperhydration: Excess total body water.

Isotonic: IV fluid overload, heart/renal failure
Hypotonic (water intoxication): excessive free water intake, SIADH → cerebral edema
Hypertonic: excessive Na administration (rare)

Edema: Accumulation of excess fluid in interstitial spaces. Dropsy: Large-scale edema (ascites, pleural effusion = effusion in body cavities).

Pathogenesis (Starling forces):

↑Capillary hydrostatic pressure → filtration ↑ (heart failure, venous obstruction)
↓Plasma oncotic pressure → filtration ↑ (hypoalbuminemia - nephrotic, hepatic, malnutrition)
↑Capillary permeability → protein leaks out (inflammation, allergy, burns)
↓Lymphatic drainage → lymphedema (filariasis, surgery)

Local vascular-tissue factors: Local prostaglandins, bradykinin, histamine increase permeability; tissue compliance determines where edema accumulates.

Q61. Pathogenesis of specific edemas

Cardiac edema: Right heart failure → venous hypertension → ↑capillary pressure → dependent edema (legs, ankles, sacral); also ↑aldosterone → Na/water retention (RAAS activation)
Hepatic edema (ascites): ↓albumin synthesis → ↓oncotic pressure; portal hypertension; ↑aldosterone (impaired hepatic degradation) → Na retention
Renal edema: Nephrotic syndrome: massive proteinuria → hypoalbuminemia → ↓oncotic pressure; nephritic: Na/water retention, oliguria
Inflammatory edema: Cytokine/histamine-mediated ↑permeability → protein-rich exudate
Toxic edema: Toxins damage endothelium → permeability ↑ (pulmonary edema in sepsis, ARDS)
Allergic edema (angioedema): Histamine/bradykinin → rapid local permeability ↑
Neurogenic edema: Neurogenic inflammation (substance P, CGRP) → local vasodilation/permeability ↑
Famine edema: Hypoalbuminemia from protein-energy malnutrition → ↓oncotic pressure

Therapy: Treat underlying cause; diuretics (furosemide for fluid removal); spironolactone in hepatic edema; albumin infusion in hypoalbuminemia.

Q62. Hypoxia

Hypoxia: Insufficient O₂ at tissue level to meet metabolic demands.

Classification:

Hypoxic (exogenous): Low PaO₂ - high altitude, hypoventilation, V/Q mismatch, diffusion impairment
Circulatory (ischemic): Reduced blood flow - heart failure, shock, arterial obstruction
Hemic (anemic): Reduced O₂ carrying capacity - anemia, CO poisoning (carboxyhemoglobin), methemoglobinemia
Histotoxic (tissue): Cells cannot use O₂ - cyanide poisoning, severe uncoupling
Respiratory: Failure of gas exchange in lungs
Mixed: Combination of types (common in clinical practice - septic shock: circulatory + histotoxic)

Prevention/therapy: Supplemental O₂ (for hypoxic type), treat underlying cause; hyperbaric O₂ for CO poisoning; antidotes (hydroxocobalamin for cyanide); blood transfusion for severe anemia.

Q63. Functional/metabolic disorders in hypoxia and adaptations

Acute functional and metabolic disorders:

Switch to anaerobic glycolysis → lactate accumulation → metabolic acidosis
ATP depletion → Na-K-ATPase failure → cellular swelling
Ca²⁺ influx → enzyme activation (phospholipases, proteases) → cell death
Free radical generation
Most sensitive: neurons (4-6 min), myocardium (20-30 min), kidneys, liver

Emergency adaptive responses:

↑Respiratory rate and depth (hyperventilation)
Tachycardia, ↑cardiac output
Redistribution of blood to vital organs
Increased O₂ extraction from blood

Long-term adaptive responses (acclimatization):

↑EPO production (kidney peritubular cells) → ↑RBC mass (polycythemia)
↑2,3-DPG in erythrocytes → rightward shift of O₂-Hb curve → better O₂ unloading
Angiogenesis (VEGF) → more capillaries in tissues
Mitochondrial biogenesis
HIF-1α transcription factor orchestrates most adaptive responses

Q64. Anemias - classification and acute posthemorrhagic anemia

Anemia: Hemoglobin <120 g/L (women) or <130 g/L (men); or reduced RBC mass.

Classification:

By etiology: blood loss, hemolysis, impaired production
By MCV: microcytic (iron deficiency, thalassemia), normocytic (hemolytic, aplastic, acute blood loss), macrocytic (B12/folate deficiency)
By reticulocyte count: regenerative (hemolytic, hemorrhagic) vs. hypo/aregenerative (aplastic, deficiency)

Acute posthemorrhagic anemia:

Etiology: Trauma, GI bleeding, surgery, obstetric hemorrhage
Pathogenesis: Rapid blood volume loss → sympathoadrenal activation → tachycardia, vasoconstriction → if >30% volume lost → hemorrhagic shock
Hematologic: Initially Hb normal (hemodilution not yet occurred); after fluid shifts: normocytic normochromic anemia; reticulocytosis peaks at 7-10 days
Therapy: Arrest bleeding, IV fluids, blood transfusion (if severe), iron supplementation for recovery

Q65. Hemolytic anemias

Hereditary:

Hereditary spherocytosis: Spectrin/ankyrin defects → spherocytes → splenic destruction; autosomal dominant; splenomegaly, jaundice; treatment: splenectomy
G6PD deficiency: X-linked; oxidative stress (fava beans, primaquine, dapsone, infections) → Heinz bodies → hemolysis; self-limiting
Sickle cell anemia (HbSS): HbS polymerizes when deoxygenated → sickle cells → vaso-occlusion, hemolysis; crises, organ damage, infections; treatment: hydroxyurea, exchange transfusion
Thalassemias: Reduced α or β globin chain synthesis → unbalanced chains → hemolysis + ineffective erythropoiesis

Acquired:

Autoimmune hemolytic anemia (AIHA): Warm (IgG, DAT+, SLE, CLL) or cold (IgM, Mycoplasma, EBV) type; treatment: steroids, rituximab, splenectomy
Microangiopathic: TTP/HUS, DIC → mechanical destruction (schistocytes)
Drug-induced: Penicillin, methyldopa, quinine

Q66. B12/folate deficiency and aplastic anemias

B12/folate deficiency anemia (megaloblastic):

Etiology:
- B12: pernicious anemia (anti-intrinsic factor antibodies), gastrectomy, Crohn's (terminal ileum), strict veganism
- Folate: poor intake, pregnancy (high demand), alcohol, methotrexate, trimethoprim
Pathogenesis: Impaired DNA synthesis → defective nuclear maturation but cytoplasm continues to grow → megaloblasts; all hematopoietic cell lines affected
Clinical: Anemia, glossitis, angular cheilitis; B12 also causes subacute combined degeneration of spinal cord (posterior + lateral columns) - NOT seen in folate deficiency
Hematologic: Macrocytic (MCV >100), hypersegmented neutrophils, pancytopenia
Therapy: IM hydroxocobalamin (B12); oral folic acid

Aplastic anemia:

Etiology: Idiopathic (most common), drugs (chloramphenicol, NSAIDs), viruses (EBV, CMV, parvovirus B19), radiation, inherited (Fanconi anemia)
Pathogenesis: T-cell-mediated destruction of hematopoietic stem cells → pancytopenia
Hematologic: Normocytic normochromic anemia + neutropenia + thrombocytopenia; hypocellular bone marrow
Therapy: Allogenic bone marrow transplant (young with matched donor); anti-thymocyte globulin + cyclosporine + eltrombopag (others)

Q67. Iron deficiency and sideroblastic anemias

Iron deficiency anemia (IDA): Most common anemia worldwide.

Etiology: Chronic blood loss (GI bleeding, menorrhagia), inadequate intake, malabsorption (celiac, post-gastrectomy), increased demand (pregnancy, growth)
Pathogenesis: Depleted iron stores → inadequate heme synthesis → microcytic hypochromic RBCs
Clinical: Fatigue, pallor, pica (craving non-food items), koilonychia (spoon nails), atrophic glossitis, angular stomatitis; Plummer-Vinson syndrome (IDA + esophageal webs + dysphagia)
Lab: ↓Hb, ↓MCV, ↓MCHC, ↓serum iron, ↓ferritin, ↑TIBC, ↑RDW
Therapy: Oral ferrous sulfate; treat underlying cause; IV iron if malabsorption; transfusion if severe

Sideroblastic anemia:

Etiology: X-linked hereditary (ALAS2 mutation), acquired (alcohol, lead, isoniazid), myelodysplastic syndrome
Pathogenesis: Impaired heme synthesis → iron accumulates in mitochondria of developing RBCs → ringed sideroblasts on Prussian blue stain
Lab: ↑serum iron, ↑ferritin, normal/↑TIBC, dimorphic blood film; ringed sideroblasts in marrow
Therapy: Pyridoxine (B6) for hereditary form and INH-induced; treat underlying cause

Q68. Erythrocytosis and Polycythemia Vera

Erythrocytosis: Increase in RBC mass (Hb >185 g/L in men, >165 g/L in women). Types:

Absolute: True increase in RBC mass
- Primary: Polycythemia vera (JAK2 mutation)
- Secondary: Appropriate (altitude, COPD, cyanotic heart disease - ↑EPO) or Inappropriate (EPO-secreting tumor: renal cell carcinoma, cerebellar hemangioblastoma, hepatocellular carcinoma)
Relative (apparent/spurious): Contracted plasma volume (dehydration, Gaisböck syndrome); RBC mass normal

Polycythemia vera (Vaquez/Wakez disease):

Etiology: Somatic JAK2 V617F mutation (>95%) or JAK2 exon 12 mutation → constitutive JAK-STAT signaling → EPO-independent erythropoiesis
Clinical: Plethoric facies, splenomegaly, pruritus after hot bath (aquagenic pruritus from histamine), hypertension, thrombosis (Budd-Chiari), bleeding, gout
Hematologic: ↑Hb, ↑Hct, often ↑WBC and ↑platelets too; ↓EPO levels; hypercellular bone marrow
Therapy: Phlebotomy, low-dose aspirin; hydroxyurea or ruxolitinib for high-risk

Q69. Leukocytosis and neutrophil nuclear shift

Leukocytosis: WBC >11 × 10⁹/L. Types:

Neutrophilia: Bacterial infection, inflammation, corticosteroids, splenectomy
Lymphocytosis: Viral infections (EBV, CMV), CLL, pertussis
Monocytosis: TB, brucellosis, monocytic leukemia
Eosinophilia: Allergies, parasites, Addison's, eosinophilic leukemia
Basophilia: CML, allergic reactions, hypothyroidism

Mechanisms:

Increased production (G-CSF, infection stimulus)
Decreased margination/tissue migration
Decreased destruction

Neutrophil nuclear shift:

Left shift: Increased band neutrophils (immature) - indicates active bacterial infection; promyelocytes/myelocytes suggest severe infection or leukemia
Right shift (hypersegmentation): >5 lobes in >5% of neutrophils - suggests megaloblastic anemia, renal failure
Diagnostic value: Left shift = regenerative response; distinguishes reactive neutrophilia (left shift, toxic granulation) from leukemia (immature blast cells)

Q70. Leukopenias

Leukopenia: WBC <4 × 10⁹/L. Types: Neutropenia (most significant), lymphopenia, eosinopenia.

Neutropenia mechanisms:

Decreased production: aplastic anemia, chemotherapy, radiation, B12/folate deficiency, marrow infiltration
Increased destruction: autoimmune neutropenia, hypersplenism, drugs (clozapine, propylthiouracil)
Redistribution: endotoxin, dialysis (margination)

Hematologic: ↓WBC; bone marrow may show reduced myeloid precursors or "arrest" at certain stage.

Significance: Infections are the major consequence; risk rises dramatically when neutrophils <0.5 × 10⁹/L (severe neutropenia); opportunistic infections common; impaired wound healing.

Q71. Agranulocytosis

Definition: Severe reduction or absence of granulocytes; absolute neutrophil count (ANC) <0.5 × 10⁹/L (sometimes <0.1 × 10⁹/L).

Types:

Immune: Drug-induced (hapten formation → antibodies destroy granulocytes; aminopyrine, clozapine, carbimazole, methimazole)
Myelotoxic: Direct bone marrow suppression (chloramphenicol, cytostatics, benzene)
Congenital: Kostmann syndrome (SCN), cyclic neutropenia

Hematologic: Absent neutrophils; bone marrow: myeloid arrest at promyelocyte stage (immune) or hypoplasia (toxic).

Significance: Life-threatening infections - Pseudomonas, fungi, gram-positive bacteria; oral ulcers, high fever are hallmarks.

Therapy: Withdraw causative drug; G-CSF (filgrastim) to stimulate production; prophylactic antibiotics/antifungals; allogenic SCT for Kostmann syndrome.

Q72. Leukemia

Definition: Malignant clonal proliferation of hematopoietic cells that accumulates in bone marrow and blood, suppressing normal hematopoiesis.

Etiology: Chromosomal translocations (BCR-ABL in CML, PML-RARA in APL), ionizing radiation, benzene, viruses (HTLV-1), chemotherapy, genetic syndromes (Down, Fanconi).

Pathogenesis: Single hematopoietic progenitor acquires oncogenic mutation → arrested differentiation + uncontrolled proliferation → accumulation of blasts/leukemic cells.

Classification:

	Acute	Chronic
Myeloid	AML (>20% blasts)	CML (BCR-ABL, Philadelphia chromosome)
Lymphoid	ALL (common in children)	CLL (most common adult leukemia)

Clinical: Bone marrow failure (anemia, infections, bleeding), organ infiltration (hepatosplenomegaly, lymphadenopathy), hyperuricemia, leukostasis (at very high WBC).

Diagnosis: Blood count, peripheral smear, bone marrow biopsy, cytogenetics, immunophenotyping, molecular markers.

Treatment: Chemotherapy; targeted therapy (imatinib for CML, FLT3/IDH inhibitors for AML); all-trans retinoic acid for APL; allogenic SCT; CAR-T cells (ALL).

Q73. Heart failure: etiology, types, pathogenesis

Heart failure: The heart cannot maintain adequate cardiac output to meet the body's metabolic demands at normal filling pressures.

Etiology:

Reduced contractility: MI, cardiomyopathy, myocarditis
Pressure overload: hypertension, aortic stenosis, pulmonary hypertension
Volume overload: valvular regurgitation, shunts
Restrictive: cardiac tamponade, constrictive pericarditis

Types:

Left vs. right vs. biventricular
Systolic (reduced EF <40%) vs. diastolic (preserved EF >50% but impaired relaxation)
Acute vs. chronic
High-output (thyrotoxicosis, severe anemia, AV fistula) vs. low-output (most common)

Hemodynamic changes:

↓Cardiac output → ↑sympathetic activity → tachycardia, vasoconstriction
↑PCWP (left HF) → pulmonary edema
↑CVP (right HF) → peripheral edema, hepatomegaly

Clinical manifestations of left HF: Dyspnea, orthopnea, PND, pulmonary rales, S3 gallop. Right HF: Peripheral edema, JVD, hepatomegaly, ascites.

Q74. Pathogenesis of chronic heart failure: compensation and decompensation

Compensatory mechanisms:

Frank-Starling mechanism: ↑preload → ↑stroke volume (operates early but limited by ventricular size)
Sympathoadrenal activation: ↑heart rate, ↑contractility, vasoconstriction (maintains BP but ↑afterload)
RAAS activation: Angiotensin II + aldosterone → Na/water retention → ↑preload
Myocardial hypertrophy:
- Concentric (pressure overload - thick walls, ↓chamber size)
- Eccentric (volume overload - dilated chamber, normal wall thickness)
Redistribution of blood flow to vital organs

Decompensation: Compensatory mechanisms become detrimental:

Hypertrophy → fibrosis → diastolic dysfunction
Chronic sympathetic activation → β-receptor downregulation → reduced responsiveness
Chronic RAAS → progressive remodeling, hypokalemia, worsening edema

Cardiac remodeling: Structural/functional changes in the failing heart:

Ventricular dilation and geometry change (spherical shape)
Myocyte hypertrophy, apoptosis, fibrosis
Fetal gene re-expression (β-myosin heavy chain, ANP)
Progressive decline in ejection fraction

Neurohormonal hypothesis: RAAS and sympathetic system are primary drivers of progression; ACEi, β-blockers, MRA target these pathways.

Q75. Acute heart failure

Acute right ventricular failure:

Causes: massive pulmonary embolism, RV infarction (right coronary artery occlusion), acute pulmonary hypertension
Manifestations: Acute JVD, hypotension, ↑CVP, clear lungs; Beck's triad in tamponade; jugular pulsation, hepatomegaly acutely
Emergency care: Volume carefully (RV preload dependent), O₂, treat cause (thrombolysis for PE, pericardiocentesis for tamponade)

Acute left ventricular failure:

Causes: Acute MI, hypertensive emergency, acute MR/AR, myocarditis
Manifestations: Acute pulmonary edema - severe dyspnea, pink frothy sputum, tachycardia, bilateral rales, hypoxemia
Emergency care:
- Sit patient up
- O₂/NIV (CPAP reduces preload)
- IV loop diuretics (furosemide - vasodilation + diuresis)
- IV nitrates (preload reduction)
- Morphine (reduces anxiety, mild vasodilation)
- If cardiogenic shock: inotropes (dobutamine), IABP, mechanical circulatory support

Q76. Coronary insufficiency and ischemic syndromes

Coronary insufficiency: Inadequate coronary blood flow relative to myocardial O₂ demand.

Types:

Fixed obstruction (atherosclerotic plaque)
Dynamic (vasospasm - Prinzmetal's angina)
Microvascular (syndrome X)

Ischemic syndromes:

Stable angina pectoris: Predictable chest pain on exertion; relief with rest/nitrates; fixed stenosis ≥70%; reversible ischemia
Unstable angina: Pain at rest or new onset/progressive; plaque rupture with non-occlusive thrombus; troponin negative
NSTEMI: Same as UA but with troponin elevation (some myocardial necrosis)
STEMI: Complete occlusion → transmural infarction; ST elevation, LBBB
Silent (painless) ischemia: Ischemia without angina; common in diabetics (autonomic neuropathy)
Stunned myocardium: Prolonged contractile dysfunction after brief ischemia despite restored flow; reversible over days-weeks
Hibernating myocardium: Chronic reduced contractility due to chronic low-flow ischemia; viable but dysfunctional; recovers after revascularization

Q77. Myocardial infarction

Definition: Irreversible myocardial necrosis from prolonged ischemia (>20-40 min). Causes: Atherosclerotic plaque rupture → thrombus → coronary occlusion; vasospasm; embolism; demand ischemia.

Types: STEMI vs. NSTEMI; transmural vs. subendocardial; anterior (LAD), inferior (RCA), lateral (LCx).

Pathogenesis of complications:

Contractility: Necrotic cells cannot contract → systolic dysfunction → ↓EF → cardiogenic shock (if >40% LV mass lost)
Arrhythmia: Ischemia → altered membrane potentials, reentry → VF/VT (most common cause of death in first hour); complete heart block (inferior MI + RCA occlusion of AV node)
Hemodynamics: ↓stroke volume → ↓BP → compensatory tachycardia; pulmonary edema if severe LV failure

Complications: Arrhythmias (VF), cardiogenic shock, mechanical complications (free wall rupture, papillary muscle rupture → acute MR, VSD), pericarditis (Dressler syndrome), LV thrombus, LV aneurysm.

Markers of myocardial damage:

Troponin I and T: Most sensitive and specific; rise at 3-6h, peak 24-48h, normalize over 7-14 days
CK-MB: Rise 3-6h, peak 12-24h; useful for reinfarction
Myoglobin: Earliest (1-2h) but not specific
LDH: Late marker, historical use

Q78. Reperfusion injury and ischemic adaptation

Reperfusion injury: Paradoxical damage that occurs upon restoration of blood flow after ischemia.

Mechanisms:

Oxidative stress: O₂ reintroduction → burst of free radicals (xanthine oxidase → O₂•⁻, H₂O₂) → membrane lipid peroxidation, protein oxidation, DNA damage
Calcium overload: Na-Ca exchanger reversal → massive Ca²⁺ entry → hypercontracture, mitochondrial permeability transition pore (mPTP) opening → cytochrome c release → apoptosis
Neutrophil activation: Reperfused tissue releases chemokines → neutrophil adhesion → proteases and free radical release
mPTP opening: Key mediator of reperfusion cell death

Manifestations: Reperfusion arrhythmias (VF), myocardial stunning, accelerated necrosis in peri-infarct zone.

Ischemic preconditioning: Brief episodes of ischemia before prolonged ischemia confer protection:

Early: within 2h; PKC activation, KATP channels, adenosine
Late (second window): 24-72h; iNOS, COX-2, HSP induction

Q79. Hypertensive disease (Essential hypertension)

Definition: Sustained BP ≥140/90 mmHg without identifiable secondary cause (primary/essential hypertension, ~95% of cases).

Etiology: Polygenic + environmental; genetic factors (RAAS gene variants, salt sensitivity genes) + excess dietary sodium, obesity, physical inactivity, alcohol, stress.

Pathogenesis:

↑Sympathetic activity + RAAS activation → ↑cardiac output and vasoconstriction → ↑BP
Renal dysfunction: impaired pressure natriuresis → Na/water retention → ↑blood volume
Vascular remodeling: smooth muscle hypertrophy → ↑peripheral resistance (self-perpetuating)
Endothelial dysfunction: ↓NO, ↑endothelin, ↑angiotensin II

Complications:

Target organ damage: LVH → heart failure; coronary artery disease
Stroke (hemorrhagic and ischemic)
Chronic kidney disease (nephrosclerosis)
Retinopathy (AV nicking, cotton-wool spots, flame hemorrhages)
Aortic dissection (hypertensive emergency)

Q80. Symptomatic (secondary) arterial hypertension

Definition: Hypertension with an identifiable underlying cause (~5% of all hypertension).

Types and causes:

Renal parenchymal: Glomerulonephritis, PKD, diabetic nephropathy → ↑RAAS, volume overload
Renovascular: Renal artery stenosis (atherosclerosis in elderly; fibromuscular dysplasia in young women) → ↑renin → ↑angiotensin II
Endocrine:
- Primary hyperaldosteronism (Conn's adenoma): Na retention + K loss
- Pheochromocytoma: Catecholamine excess → episodic hypertension, sweating, headache, palpitations
- Cushing's syndrome: Cortisol → mineralocorticoid effect + insulin resistance
- Hypothyroidism (diastolic hypertension); Hyperthyroidism (systolic)
Aortic coarctation: Upper extremity hypertension, rib notching
Drugs/substances: OCP, NSAIDs, cocaine, amphetamines, cyclosporine, EPO

Q81. Arterial hypotension and collapse

Arterial hypotension: BP <90/60 mmHg (systolic). Types:

Physiological: Trained athletes, constitutional
Orthostatic (postural): ≥20/10 mmHg drop on standing; autonomic failure, dehydration, drugs
Symptomatic: Secondary to disease (cardiac failure, Addison's, hypothyroidism, sepsis)

Collapse: Acute vascular insufficiency → abrupt fall in BP → insufficient perfusion of vital organs. Types:

Orthostatic: Venous pooling on position change
Cardiac: Arrhythmia, MI, tamponade
Vascular (distributive): Sepsis, anaphylaxis, drugs, neurogenic (vasovagal, spinal shock)
Hemorrhagic/hypovolemic: Volume loss

Mechanisms: Decreased venous return → decreased cardiac output OR decreased vascular resistance → BP falls → brain/organ hypoperfusion → loss of consciousness.

Q82. Respiratory failure: definition, causes, types

Respiratory failure (RF): Inability of the respiratory system to maintain adequate gas exchange; PaO₂ <60 mmHg (hypoxemia) and/or PaCO₂ >50 mmHg (hypercapnia).

Types:

Type I (hypoxemic): Low PaO₂, normal/low PaCO₂; V/Q mismatch, shunt, diffusion impairment (ARDS, pneumonia, PE, pulmonary edema)
Type II (hypercapnic/ventilatory): ↑PaCO₂ + ↓PaO₂; alveolar hypoventilation (COPD, neuromuscular disease, overdose)
Acute vs. chronic

Causes:

Central: CNS depression (drugs, stroke, trauma)
Peripheral neuromuscular: GBS, myasthenia, SCI, phrenic nerve palsy
Chest wall/pleural: flail chest, pleural effusion, pneumothorax
Airway: obstruction, severe bronchospasm (asthma, COPD)
Parenchymal: pneumonia, ARDS, pulmonary fibrosis, pulmonary edema

Recognition: ABG analysis; ↓SpO₂; clinical: tachypnea, accessory muscle use, cyanosis, altered mentation.

Q83. Ventilatory disorders in respiratory failure

Hypoventilation: Reduced alveolar minute ventilation → CO₂ retention → hypercapnia + hypoxemia.

Obstructive hypoventilation:

Causes: COPD, asthma, bronchitis, foreign body
Mechanism: ↑airway resistance → air trapping → hyperinflation → ↑work of breathing
Recognition: prolonged expiration, wheeze, ↑RV/FRC, ↓FEV1/FVC

Restrictive hypoventilation:

Causes: Pulmonary fibrosis, pleural effusion, pneumothorax, kyphoscoliosis, neuromuscular (GBS, myasthenia, MND)
Mechanism: ↓compliance or ↓respiratory muscle force → small tidal volumes
Recognition: ↓TLC, ↓FVC, normal or ↑FEV1/FVC ratio

Dysregulatory hypoventilation:

Causes: CNS depression (opioids, barbiturates, stroke, trauma, Ondine's curse - failure of automatic breathing control)
Mechanism: ↓respiratory drive → reduced respiratory frequency and/or depth
Recognition: reduced respiratory rate, PCO₂ elevation; responds to naloxone (if opioid)

Q84. Diffusion impairment and V/Q mismatch

Diffusion impairment:

Causes: Pulmonary fibrosis (alveolar wall thickening - increased diffusion distance), pulmonary edema, pneumonia
Mechanism: Fick's law: diffusion rate ∝ (area × ΔP)/thickness; ↑thickness → ↓O₂ transfer (CO₂ diffuses 20× faster, so CO₂ retention rare with diffusion alone)
Recognition: Hypoxemia; worsens on exercise; ↓DLCO (diffusing capacity for CO)

V/Q mismatch:

V/Q > normal (dead space effect): Ventilation with no perfusion (PE) → wasted ventilation; ↑PaCO₂ if severe
V/Q < normal (shunt effect): Perfusion with no ventilation (consolidation, atelectasis, ARDS) → venous blood passes to arterial circulation → hypoxemia; does NOT respond well to supplemental O₂ (true shunt)

Recognition of V/Q mismatch: A-a gradient elevated; responds to O₂ (if V/Q mismatch, not pure shunt).

Q85. ARDS (Adult Respiratory Distress Syndrome)

Definition: Acute hypoxemic respiratory failure with bilateral pulmonary infiltrates not explained by cardiac failure/fluid overload; PaO₂/FiO₂ ratio <300 (Berlin criteria).

Causes:

Pulmonary (direct): Severe pneumonia, aspiration, near-drowning, pulmonary contusion
Extrapulmonary (indirect): Sepsis (most common), massive transfusion, pancreatitis, trauma, burns

Mechanisms:

Triggering event → neutrophil activation and sequestration in lung
Neutrophil degranulation → proteases, ROS → alveolar epithelial and capillary endothelial damage
Exudative phase (0-7d): protein-rich edema, hyaline membrane formation, surfactant loss → atelectasis → ↓compliance, shunt
Proliferative phase (7-21d): Type II pneumocyte proliferation, fibroblast activation
Fibrotic phase: Collagen deposition → irreversible restriction

Recognition: Acute onset within 1 week; bilateral opacities on imaging; PaO₂/FiO₂ <300; exclude cardiogenic edema (PCWP <18 mmHg or no evidence of cardiac failure).

Q86. Pulmonary hypertension

Definition: Mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest.

Types (WHO Classification):

Pulmonary arterial hypertension (PAH): idiopathic, heritable (BMPR2 mutation), drugs/toxins
Left heart disease (most common): elevated PCWP transmitted to pulmonary circulation
Lung disease/hypoxia: COPD, ILD, OSA → hypoxic vasoconstriction
Chronic thromboembolic PH (CTEPH): organized thrombi in pulmonary arteries
Multifactorial: sarcoidosis, histiocytosis, metabolic disorders

Mechanisms:

Vasoconstriction: hypoxia → ↑endothelin, ↓NO, ↓prostacyclin → smooth muscle constriction
Vascular remodeling: smooth muscle hypertrophy, intimal fibrosis → obliterative lesions (plexogenic arteriopathy)

Compensation: RV hypertrophy → maintains output against ↑afterload; eventually RV failure (cor pulmonale).

Q87. Respiratory act disorders and asphyxia

Types of abnormal breathing:

Dyspnea: Subjective sensation of difficult/labored breathing
Tachypnea: ↑respiratory rate (>20/min)
Bradypnea: ↓respiratory rate
Hyperpnea: ↑depth and rate (exercise, acidosis)
Kussmaul breathing: Deep, regular, sighing (diabetic ketoacidosis - respiratory compensation for metabolic acidosis)
Cheyne-Stokes: Waxing-waning amplitude then apnea; CNS lesions, severe HF, high altitude; mechanism: oscillation of CO₂ sensitivity
Biot's: Irregular breathing with apnea; severe medullary damage
Apnea: Cessation of breathing
Agonal breathing: Gasping before death

Asphyxia: Condition of severely deficient supply of O₂ to the body combined with CO₂ accumulation. Causes: Airway obstruction (strangulation, drowning, choking), chest compression, neuromuscular paralysis.

Stages:

Dyspnea stage: Hypoxemia/hypercapnia → ↑RR and depth, cyanosis, hypertension
Convulsive stage: Severe hypoxia → tonic-clonic convulsions, loss of consciousness, bradycardia
Apnea stage: Respiratory center depression → apnea, ↓BP
Terminal stage: Agonal gasps, cardiac arrest

Q88. Digestive insufficiency

Definition: Inability of the digestive system to provide adequate nutrient processing and absorption.

Causes:

Insufficient secretion (enzymes, HCl, bile)
Motility disorders
Mucosal damage
Neurological and hormonal dysregulation

Influence of alcohol on digestion:

Stimulates gastric acid (low doses) but damages mucosa (high doses) → gastritis, ulcers
Inhibits pancreatic secretion → maldigestion
Damages intestinal epithelium → malabsorption
Causes pancreatitis (acute and chronic)
Impairs liver function → bile salt deficiency → fat malabsorption, steatorrhea
Inhibits ADH → diuresis → dehydration

Q89. Oral/esophageal disorders

Taste disorders: Ageusia (total loss), hypogeusia, dysgeusia; causes: zinc deficiency, cranial nerve VII/IX damage, medications, infections.

Appetite disorders:

Anorexia: CNS (hypothalamic dysfunction), hormonal (ghrelin/leptin dysregulation), malignancy, depression
Bulimia/polyphagia: hyperthyroidism, DM, hypothalamic lesions

Chewing disorders: Dental loss, temporomandibular disease, facial nerve palsy, trismus (tetanus).

Salivation disorders:

Hyposalivation (xerostomia): Sjögren's syndrome, anticholinergic drugs, radiation → impaired bolus formation, dental caries, dysgeusia
Hypersalivation: parasympathomimetics, esophageal obstruction, nausea

Swallowing disorders (dysphagia):

Oropharyngeal: neurological (stroke, MG, Parkinson's), structural
Esophageal: mechanical (stricture, cancer, foreign body) or motility (achalasia, diffuse esophageal spasm, scleroderma)

Motor function of esophagus: Primary peristalsis (swallowing-triggered), secondary (distension-triggered); achalasia = failure of LES relaxation (↓VIP/NO) + absent peristalsis.

Q90. Gastric disorders and peptic ulcer

Gastric secretory disorders:

Hyperchlorhydria: ↑HCl → risk of peptic ulcer, esophagitis
Hypochlorhydria/achlorhydria: pernicious anemia (anti-parietal cell antibodies → ↓IF → ↓B12), atrophic gastritis, PPIs
Hyperpepsinogenemia: risk factor for peptic ulcer

Peptic ulcer disease:

Etiology: H. pylori infection (most common, ~70-90% of duodenal ulcers), NSAIDs (inhibit COX-1 → ↓PGE₂ → ↓mucus/bicarbonate/mucosal blood flow), Zollinger-Ellison syndrome (gastrinoma → extreme acid hypersecretion)
Pathogenesis: Imbalance between aggressive factors (HCl, pepsin, H. pylori, NSAIDs) and defensive factors (mucus, bicarbonate, prostaglandins, mucosal blood flow, epithelial renewal)
Manifestations: Epigastric pain (duodenal: relieved by food; gastric: worsened by food), bloating, heartburn; complications: hemorrhage, perforation, obstruction, malignant transformation (gastric ulcer)

Q91. Intestinal digestion disorders

Cavity (luminal) digestion disorders:

Pancreatic exocrine insufficiency: ↓proteases, lipases, amylase → protein/fat/carbohydrate maldigestion (chronic pancreatitis, CF, pancreatic cancer)
Bile salt deficiency: ↓fat emulsification and micelle formation → steatorrhea (obstructive jaundice, terminal ileal disease/resection → bile salt malabsorption)
↓brush border enzymes: lactase deficiency → lactose intolerance

Wall (parietal) digestion disorders: Celiac disease (gluten-induced villous atrophy → ↓brush border), Whipple's disease.

Maldigestion: Impaired breakdown of nutrients. Malabsorption: Impaired nutrient uptake from intestine.

Malabsorption syndrome: Diarrhea (steatorrhea), weight loss, nutritional deficiencies; causes include celiac disease, Crohn's disease, short bowel syndrome, radiation enteritis.

Q92. Intestinal motility disorders

Diarrhea: >3 loose stools/day or >200g/day stool weight. Types:

Secretory: Toxins (cholera toxin) activate adenylate cyclase → ↑cAMP → massive Cl⁻/water secretion; large volume, watery; persists with fasting
Osmotic: Unabsorbed osmotically active substances (lactose intolerance, lactulose, Mg²⁺) draw water into lumen; stops with fasting
Exudative (inflammatory): Mucosal inflammation → bloody/mucous stool (IBD, dysentery, invasive bacteria)
Motility: Rapid transit → insufficient absorption (hyperthyroidism, IBS-D, post-vagotomy)

Constipation: Infrequent, difficult passage of hard stool. Types:

Atonic: Reduced smooth muscle tone (elderly, hypothyroidism, low fiber, dehydration, sedentary)
Spastic: Excessive segmental contractions (IBS-C, anxiety)
Obstructive: Mechanical blockage (tumor, stricture, Hirschsprung's)

Intestinal obstruction:

Mechanical: Physical blockage - adhesions, hernias, tumor, volvulus, intussusception
Dynamic (paralytic ileus): Absent peristalsis - post-surgery, peritonitis, severe electrolyte imbalance
Consequences: Fluid/electrolyte loss into lumen, bacterial overgrowth → endotoxin absorption → systemic sepsis → multi-organ failure. Intestinal autointoxication = absorption of bacterial toxins and putrefactive products through damaged mucosa.

Q93. Liver insufficiency

Types:

Acute (acute liver failure): Massive hepatic necrosis (fulminant; paracetamol overdose, viral hepatitis B/E)
Chronic: Progressive hepatocyte loss and fibrosis (cirrhosis - from alcoholism, NASH, viral hepatitis, Wilson's, hemochromatosis)

Pathogenesis of main manifestations:

Metabolic disorders: ↓glycogen storage → hypoglycemia; ↓albumin synthesis → edema, ascites; ↓clotting factors (I, II, V, VII, IX, X) → bleeding; ↓detoxification of ammonia → hepatic encephalopathy
Jaundice: Impaired bilirubin conjugation and secretion
Portal hypertension: Fibrosis → ↑hepatic resistance → varices, splenomegaly, caput medusae, ascites
Hepatorenal syndrome: Splanchnic vasodilation → renal vasoconstriction → oliguria
Endocrine: ↓sex hormone metabolism → gynecomastia, spider angiomata, palmar erythema, testicular atrophy

Q94. Liver coma

Hepatic coma (hepatic encephalopathy - HE): Neuropsychiatric dysfunction from liver failure; spectrum from Grade I (confusion, asterixis) to Grade IV (unresponsive coma).

Types:

Endogenous (true hepatic coma): Massive liver necrosis → hepatocytes cannot detoxify → toxic metabolites in brain
Exogenous (portosystemic HE): Portal-systemic shunting → intestinal toxins bypass liver → reach brain

Mechanisms:

Ammonia toxicity: Gut bacteria produce NH₃ → bypasses liver → crosses BBB → glutamate consumed to make glutamine → astrocyte swelling (cerebral edema), impairs α-KG (citric acid cycle)
False neurotransmitters: Aromatic amino acids (phenylalanine, tyrosine) compete with branched-chain AAs for transport → false NTs (octopamine, phenylethanolamine) replace norepinephrine/dopamine
GABA-ergic hypothesis: Intestinal GABA → ↑inhibitory tone
Benzodiazepine-like substances from intestinal flora

Therapy: Lactulose (traps NH₃ as NH₄⁺ in stool), rifaximin (reduces gut bacteria), protein restriction (short-term), correct precipitants (bleeding, infection, electrolyte disorders), liver transplantation.

Q95. Jaundice

Jaundice: Yellow discoloration of skin/sclerae from hyperbilirubinemia (total bilirubin >35-40 μmol/L).

Types:

Feature	Prehepatic (hemolytic)	Hepatic (hepatocellular)	Posthepatic (obstructive)
Cause	Excess RBC destruction	Hepatocyte damage	Bile duct obstruction
Bilirubin	Unconjugated ↑	Both ↑	Conjugated ↑
Urine color	Normal	Dark (urobilinogen + bilirubin)	Dark (conjugated bili)
Stool	Normal/dark	Pale	Pale (acholic)
Urine bilirubin	Negative	Positive	Positive
ALT/AST	Normal	↑↑	Normal/mild ↑
ALP/GGT	Normal	Mild ↑	↑↑
Pruritus	No	Variable	Yes (bile salt deposition)

Q96. Acute renal failure (AKI)

Definition: Rapid decline in renal function over hours-days → ↑creatinine/urea, ↓GFR, ±oliguria.

Etiology (prerenal/renal/postrenal):

Prerenal (55-60%): Hypoperfusion (hypovolemia, heart failure, sepsis, renal artery stenosis) → ↓GFR without intrinsic damage initially; fractional excretion of Na <1%
Intrinsic renal (35-40%):
- Tubular (ATN - most common intrinsic): ischemia prolonged, nephrotoxins (aminoglycosides, contrast, myoglobin)
- Glomerular: RPGN, vasculitis
- Interstitial: drug-induced AIN, infection
- Vascular: HUS/TTP, emboli
Postrenal (5%): Obstruction (BPH, calculi, tumor, pelvic malignancy)

Pathogenesis of oliguria: ATN → tubular cell necrosis → cast obstruction → back-leak of filtrate + afferent arteriolar vasoconstriction → ↓GFR.

Manifestations: Oliguria (<400 mL/day), azotemia (↑BUN, creatinine), hyperkalemia, metabolic acidosis, fluid overload, uremic symptoms (nausea, confusion, pericarditis).

Q97. Glomerulonephritis, pyelonephritis, nephrotic syndrome

Glomerulonephritis (GN):

Etiology: Immune complex deposition (post-streptococcal GN, lupus nephritis, IgA nephropathy), anti-GBM antibodies (Goodpasture), ANCA-associated vasculitis
Pathogenesis: Immune complexes in glomeruli → complement activation → neutrophil infiltration → mesangial expansion, BM damage → proteinuria, hematuria, ↓GFR
Manifestations: Nephritic syndrome (hematuria, hypertension, edema, oliguria, mild proteinuria)

Pyelonephritis:

Etiology: Ascending infection (E. coli 80%, Klebsiella, Proteus); risk factors: urinary obstruction, reflux, DM, instrumentation
Pathogenesis: Bacteria reach renal pelvis → interstitial inflammation, tubular damage
Manifestations (acute): Flank pain/costovertebral angle tenderness, fever/chills, dysuria; pyuria, bacteriuria, WBC casts

Nephrotic syndrome:

Causes: Minimal change disease (children), FSGS, membranous nephropathy, diabetic nephropathy, amyloidosis
Pathogenesis: Damage to podocytes/filtration barrier → massive proteinuria (>3.5 g/day) → hypoalbuminemia → ↓oncotic pressure → edema + ↑RAAS → more edema; ↑lipoproteins (dyslipidemia); lipiduria
Manifestations: Massive pitting edema, frothy urine, hypoalbuminemia, hyperlipidemia, lipiduria, hypercoagulability (loss of AT-III, protein C/S)

Q98. Chronic kidney disease (CKD)

Definition: Kidney damage or GFR <60 mL/min/1.73m² for ≥3 months.

Etiology: DM (most common ~35%), hypertension (~25%), GN, ADPKD, analgesic nephropathy, obstructive uropathy.

Pathogenesis: Initial nephron loss → compensatory hyperfiltration in remaining nephrons → glomerular hypertension → further sclerosis → progressive decline (Brenner hypothesis). TGF-β mediates fibrosis.

Stages (GFR-based):

Stage	GFR	Manifestations
G1	>90	Normal (marker of damage present)
G2	60-89	Mild ↓, usually asymptomatic
G3a/b	30-59	Moderate; anemia (↓EPO), mild hyperparathyroidism begins
G4	15-29	Severe; uremic symptoms begin
G5 (ESKD)	<15	Full uremic syndrome

Manifestations: Hypertension, edema, anemia (↓EPO), renal osteodystrophy (secondary hyperparathyroidism - ↑PTH due to ↓calcitriol, hyperphosphatemia), metabolic acidosis, hyperkalemia, uremic pericarditis, neuropathy, immune suppression.

Therapy: BP control (ACEi/ARB), glycemic control, reduce protein intake; erythropoiesis-stimulating agents, phosphate binders, vitamin D analogs.

Hemodialysis: Blood pumped through semipermeable membrane, toxins diffuse into dialysate; 3×/week 4h sessions. Kidney transplant: Definitive treatment; requires immunosuppression (tacrolimus, mycophenolate, steroids).

Q99. Thyroid disorders

Hypothyroidism:

Etiology: Hashimoto's thyroiditis (autoimmune, most common), post-thyroidectomy, post-radioiodine, iodine deficiency (endemic goiter), congenital (cretinism)
Pathogenesis: ↓T3/T4 → ↑TRH/TSH → compensatory (but ineffective) enlargement
Manifestations: Fatigue, cold intolerance, bradycardia, constipation, dry skin, myxedema (non-pitting edema - GAG accumulation), ↑TSH, ↓T4
Therapy: Levothyroxine (T4 replacement)

Hyperthyroidism:

Etiology: Graves' disease (TRAb - stimulating TSH-receptor antibodies), toxic multinodular goiter, toxic adenoma, subacute thyroiditis (release phase)
Pathogenesis: ↑T3/T4 → ↑BMR, ↑adrenergic sensitivity
Manifestations: Weight loss despite good appetite, heat intolerance, sweating, palpitations, tremor, diarrhea, exophthalmos and pretibial myxedema (Graves' only), ↓TSH, ↑T3/T4
Therapy: Antithyroid drugs (methimazole, PTU), radioiodine ablation, surgery; beta-blockers for symptoms

Q100. Adenohypophysis disorders

Hyperpituitarism (excess hormone secretion):

Acromegaly/Gigantism: GH excess from pituitary adenoma; before epiphyseal closure → gigantism; after → acromegaly (enlarged hands/feet/jaw, coarsened features, organomegaly, DM, hypertension, carpal tunnel); elevated IGF-1, non-suppressible GH with glucose
Cushing's disease: ACTH-secreting pituitary adenoma → bilateral adrenal hyperplasia → cortisol excess → central obesity, buffalo hump, striae, hypertension, DM, osteoporosis, immune suppression
Prolactinoma: Most common pituitary tumor; ↑prolactin → galactorrhea, amenorrhea (women), hypogonadism (men); treatment: dopamine agonists (cabergoline)
TSH/LH/FSH-producing: Rare; hyperthyroidism or gonadal hyperstimulation

Hypopituitarism:

Causes: Pituitary adenoma mass effect, Sheehan's syndrome (postpartum infarction), trauma, irradiation, infiltration (sarcoidosis, hemochromatosis)
Manifestations: Deficiency of target organ hormones; deficiencies appear in order: GH first, then LH/FSH, TSH, ACTH last; panhypopituitarism = all deficient
Therapy: Hormone replacement (hydrocortisone for ACTH deficiency - critical; levothyroxine; sex hormones; GH)

Q101. Neurohypophysis disorders

Posterior pituitary (neurohypophysis) releases:

ADH (vasopressin, AVP): Water reabsorption in collecting duct; also vasoconstriction (V1 receptor)
Oxytocin: Uterine contractions, milk ejection, social bonding

ADH deficiency - Diabetes Insipidus (DI):

Central DI: Damage to hypothalamus/posterior pituitary (trauma, surgery, tumors, Langerhans cell histiocytosis) → ↓ADH production
Nephrogenic DI: Renal resistance to ADH (lithium toxicity, hypercalcemia, congenital V2 receptor mutation)
Manifestations: Massive polyuria (10-20 L/day), dilute urine (specific gravity <1.005), polydipsia; dehydration and hypernatremia if unable to drink
Therapy: Central: intranasal DDAVP (synthetic ADH analog); Nephrogenic: low Na diet, thiazides, indomethacin; treat underlying cause

ADH excess (SIADH):

Causes: CNS disease, pulmonary disease (SCLC, TB), drugs (carbamazepine, SSRIs, cyclophosphamide), surgery/pain
Manifestations: Hyponatremia, concentrated urine despite low serum Na, normovolemia; symptoms: confusion, seizures, coma
Therapy: Fluid restriction; tolvaptan (V2 antagonist) for severe; slow Na correction to prevent osmotic demyelination

Intermediate lobe: MSH (melanocyte-stimulating hormone) - pigmentation; POMC-derived.

Q102. Adrenal cortex (tubular/reticular zone) and medulla disorders

Tubular zone (zona glomerulosa - mineralocorticoids):

Hyperaldosteronism (Conn's syndrome): Aldosterone-secreting adenoma or bilateral hyperplasia
- Pathogenesis: ↑Na reabsorption + ↑K/H secretion in collecting duct
- Manifestations: Hypertension, hypokalemia, metabolic alkalosis, suppressed renin
Hypoaldosteronism: Addison's disease, ACE inhibitors, heparin, hyporeninemichypoaldosteronism (type 4 RTA)

Reticular zone (zona reticularis - androgens):

Excess (CAH - congenital adrenal hyperplasia): 21-hydroxylase deficiency most common → ↓cortisol → ↑ACTH → adrenal hyperplasia → shunting to androgens → virilization; salt-wasting form also has ↓mineralocorticoids
Adrenarche: Normal increase in adrenal androgens in puberty

Adrenal medulla:

Pheochromocytoma: Catecholamine-secreting tumor (NE > E typically); "rule of 10%": 10% bilateral, 10% malignant, 10% extra-adrenal (paraganglioma), 10% pediatric
Manifestations: Episodic hypertension (or sustained), headache, sweating, palpitations, pallor; hyperglycemia; hypertensive crisis triggered by surgery, medications, palpation
Diagnosis: 24h urine metanephrines/catecholamines; plasma free metanephrines; imaging (CT/MRI)
Therapy: Alpha-blockade first (phenoxybenzamine/doxazosin), THEN beta-blockade, THEN surgical resection

Q103. Adrenal cortex bundle zone (fasiculata) - glucocorticoids

Bundle zone (zona fasciculata): Produces cortisol (glucocorticoid).

Cortisol excess (Cushing's syndrome):

ACTH-dependent: Cushing's disease (pituitary adenoma - most common), ectopic ACTH (SCLC, carcinoid)
ACTH-independent: Adrenal adenoma/carcinoma, exogenous glucocorticoid use (iatrogenic - most common overall)
Manifestations: Central obesity, moon face, buffalo hump, plethoric facies, purple striae, proximal myopathy, hypertension, osteoporosis, DM, immune suppression, thin skin, easy bruising

Cortisol deficiency:

Acute adrenal insufficiency (adrenal crisis): Sudden cortisol lack; triggers: stress in chronic insufficiency, abrupt steroid withdrawal (most common), bilateral adrenal hemorrhage (Waterhouse-Friderichsen syndrome in meningococcemia)
- Manifestations: Shock (hypotension refractory to fluids/vasopressors), nausea, vomiting, confusion; if primary: also ↓aldosterone → hyperkalemia, hyponatremia
- Treatment: Immediate hydrocortisone 100 mg IV bolus + continuous IV, saline resuscitation, glucose (hypoglycemia common)
Chronic adrenal insufficiency (Addison's disease): Autoimmune adrenalitis (most common), TB, HIV, bilateral adrenal metastases; ↑ACTH → hyperpigmentation; hyponatremia, hyperkalemia, hypoglycemia, fatigue, anorexia, weight loss

Corticosteroid therapy:

Indications: Adrenal insufficiency, anti-inflammatory (asthma, COPD, IBD, RA), immunosuppression (transplant, autoimmune diseases), cerebral edema (dexamethasone)
Contraindications (relative): Active infections (especially TB, fungal), peptic ulcer, osteoporosis, DM, hypertension, psychiatric illness
Complications: Cushing's phenotype, osteoporosis, adrenal suppression (cannot stop abruptly), DM, hypertension, cataracts, glaucoma, GI ulcers, immune suppression

Q104. Motor disorders in spinal cord and brainstem lesions

Paralysis: Complete loss of voluntary movement. Paresis: Partial loss of voluntary movement/strength.

Upper motor neuron (UMN) lesion (spinal cord or brainstem):

Spastic paralysis/paresis (initially flaccid then spastic)
↑Muscle tone (spasticity)
Hyperreflexia (deep tendon reflexes ↑)
Positive Babinski sign (extensor plantar response)
No muscle atrophy (or disuse atrophy only)
Clonus may be present

Lower motor neuron (LMN) lesion:

Flaccid paralysis
↓/absent reflexes
Muscle atrophy, fasciculations
Negative Babinski

Decerebrate rigidity (decerebration): Lesion at midbrain level (between red nucleus and vestibular nuclei) → release of pontine and vestibular centers → unopposed extension of all limbs, hyperextension of neck; extension posturing.

Decorticate rigidity: Lesion above red nucleus (cortex, internal capsule) → arms flexed, wrists flexed, legs extended; indicates less severe brainstem compromise than decerebrate.

Spinal shock: Immediately after complete transverse spinal injury → flaccid paralysis, areflexia, loss of all sensation, loss of autonomic control (bowel, bladder, BP) below lesion; lasts hours-days-weeks; followed by spastic phase as reflex arcs recover.

Q105. Extrapyramidal and cerebellar motor disorders

Extrapyramidal system: Basal ganglia circuits that modulate motor cortex output for smooth, coordinated movement.

Basal ganglia lesions:

Parkinson's disease: Loss of dopaminergic neurons in substantia nigra → ↓DA in striatum → ↓inhibition of indirect pathway → ↑GPi inhibition of thalamus → ↓motor cortex activation
- Manifestations: TRAP: Tremor (resting, "pill-rolling"), Rigidity (cogwheel/lead pipe), Akinesia/Bradykinesia, Postural instability
Huntington's disease: Loss of striatal (caudate) neurons (GABAergic) → ↑DA activity → hyperkinesia (chorea), dementia
Hemiballismus: Subthalamic nucleus lesion → contralateral wild flinging movements
Athetosis: Slow writhing movements; basal ganglia damage
Chorea: Random, involuntary brief movements; Huntington's, rheumatic fever (Sydenham's chorea)

Cerebellar lesions:

Ipsilateral manifestations (cerebellum controls same side)
Ataxia: Uncoordinated gait (wide-based, truncal swaying)
Dysmetria: Past-pointing (finger-nose test), overshoot/undershoot
Dysdiadochokinesia: Inability to perform rapid alternating movements
Intention tremor: Tremor that worsens as hand approaches target (contrast with Parkinson's resting tremor)
Nystagmus: Fast phase toward lesion
Dysarthria: Scanning/cerebellar speech

Q106. Sensory disorders and pain

Sensory disorders:

Hypesthesia: Reduced sensation
Anesthesia: Complete loss of sensation (tactile, pain, temperature)
Hyperesthesia: Increased sensitivity
Dysesthesia: Abnormal unpleasant sensation
Paresthesia: Abnormal spontaneous sensations (tingling, "pins and needles")
Allodynia: Painful response to normally non-painful stimulus

Central sensory lesions:

Thalamic lesions → contralateral hemisensory loss; thalamic pain (burning, aching)
Cortical (parietal lobe) → contralateral sensory inattention, astereognosis, graphesthesia loss

Peripheral lesions:

Mononeuropathy: single nerve distribution
Polyneuropathy: glove-stocking distribution (distal symmetric); DM, alcohol, B12 deficiency

Pain: Types:

Nociceptive (somatic): Well-localized; tissue damage stimulates nociceptors; protective function
Nociceptive (visceral): Poorly localized; dull, crampy; often referred
Neuropathic: Damage to nervous system; burning, shooting, allodynia; DM, postherpetic neuralgia, phantom limb
Referred pain: Visceral pain perceived in somatic area (e.g., cardiac pain in left arm via C8-T5 convergence; diaphragm irritation → shoulder tip via C3-5)

Mechanisms:

Peripheral sensitization: prostaglandins, bradykinin, substance P lower nociceptor threshold → primary hyperalgesia
Central sensitization: wind-up, long-term potentiation in dorsal horn → secondary hyperalgesia, allodynia

Significance: Protective (warns of tissue damage), diagnostic (location, character, radiation indicates organ); pathological pain has no protective value and requires treatment.

Q107. Shock

Definition: Life-threatening circulatory failure with inadequate tissue perfusion → cellular dysfunction → multi-organ failure.

Etiology and types:

Type	Mechanism	Examples
Hypovolemic	↓Preload (↓blood volume)	Hemorrhage, burns, dehydration, vomiting/diarrhea
Cardiogenic	↓Pump function	MI, arrhythmia, cardiac tamponade
Distributive	↓Vascular resistance / maldistribution	Septic, anaphylactic, neurogenic (spinal shock)
Obstructive	Mechanical outflow obstruction	Massive PE, tension pneumothorax

Pathogenesis (stages):

Compensated shock: SNS activation → tachycardia, vasoconstriction, ↑contractility; BP maintained; oliguria begins
Decompensated (progressive) shock: Compensation fails → ↓BP; anaerobic metabolism → lactic acidosis; vasoconstriction worsens ischemia
Irreversible shock: Cell death; mediator cascade (cytokines, NO); multi-organ failure; death

Similarities across types: Hypotension, tachycardia, oliguria, altered consciousness, impaired tissue perfusion. Differences: Cold/clammy (cardiogenic, hypovolemic) vs. warm/flushed skin (distributive - early septic); JVD present in cardiogenic/obstructive; ↑CVP in cardiogenic vs. ↓CVP in hypovolemic.

Therapy principles:

Restore perfusion: IV fluids (except cardiogenic shock - cautious fluid), vasopressors (norepinephrine first-line for septic shock)
Treat cause: antibiotics/source control (septic), epinephrine (anaphylactic), reperfusion (cardiogenic from MI), decompression (obstructive)
Organ support: mechanical ventilation, renal replacement therapy

These answers are based on standard pathophysiology principles. For exam preparation, review your course-specific textbooks and lectures for any local variations in classification or terminology used by your institution.

Make a comparison table of pathophysiology mechanisms

Here is a comprehensive comparison table of key pathophysiology mechanisms from your exam syllabus:

Pathophysiology Mechanisms - Comparison Table

1. Types of Hypersensitivity (Gell & Coombs)

Feature	Type I (Anaphylactic)	Type II (Cytotoxic)	Type III (Immune Complex)	Type IV (Delayed)
Mediator	IgE	IgG / IgM	IgG / IgM complexes	T lymphocytes (TH1, CTL)
Antigen location	Soluble (environmental)	Cell surface / matrix	Soluble (circulating)	Cell-associated / intracellular
Effector mechanism	Mast cell / basophil degranulation	Complement + ADCC	Complement activation + neutrophil infiltration	Macrophage activation, cytotoxic T cells
Onset	Minutes	Minutes-hours	6-21 hours	48-72 hours
Key mediators	Histamine, leukotrienes, PGE₂, PAF	Complement (MAC), FcR on NK cells	C3a, C5a, neutrophil proteases, ROS	IFN-γ, TNF-α, IL-2, perforin/granzymes
Clinical examples	Anaphylaxis, asthma, urticaria, atopic dermatitis	Autoimmune hemolytic anemia, Goodpasture syndrome, transfusion reaction	Serum sickness, SLE, post-strep GN, Arthus reaction	Contact dermatitis, TB test, graft rejection, Hashimoto's
Skin test	Wheal & flare (15 min)	—	Arthus (4-8h)	Induration (48-72h)
Tissue infiltrate	Eosinophils, mast cells	Neutrophils (acute)	Neutrophils + monocytes	Lymphocytes + macrophages

2. Types of Shock

Feature	Hypovolemic	Cardiogenic	Septic (Distributive)	Anaphylactic	Neurogenic	Obstructive
Primary defect	↓Blood volume	↓Cardiac pump	↓Vascular resistance	↓Vascular resistance (IgE)	↓Sympathetic tone	Mechanical outflow block
Cause	Hemorrhage, burns, dehydration	MI, arrhythmia, tamponade	Gram-negative sepsis (LPS)	Penicillin, bee venom, peanuts	Spinal cord injury, spinal anesthesia	Massive PE, tension pneumothorax
CO/CI	↓↓	↓↓	↑ (early) / ↓ (late)	↓	↓	↓↓
SVR	↑↑ (compensatory)	↑↑	↓↓	↓↓	↓↓	↑
CVP/Preload	↓	↑	↓	↓	↓	↑ (obstructive)
Skin	Cold, pale, clammy	Cold, pale, clammy	Warm, flushed (early)	Flushed, urticaria	Warm, dry	Cold, pale
Pulse	Rapid, weak	Rapid, weak	Bounding (early)	Rapid, weak	Slow (bradycardia)	Rapid, weak
First-line treatment	IV fluids + stop bleeding	Inotropes (dobutamine), IABP	Norepinephrine + antibiotics	Epinephrine IM 0.5 mg	Vasopressors + fluids	Decompress (PE: thrombolysis; PTX: needle)
Distinguishing sign	History of blood/fluid loss	S3 gallop, pulmonary edema, ↑PCWP	Fever, +blood cultures, warm peripheries	Urticaria, angioedema, allergen exposure	Bradycardia with hypotension	JVD + clear lungs OR absent breath sounds

3. Types of Hypoxia

Feature	Hypoxic	Circulatory (Ischemic)	Hemic (Anemic)	Histotoxic	Respiratory
Cause	Low PaO₂ (altitude, hypoventilation, V/Q mismatch)	↓Blood flow (heart failure, shock)	↓O₂ carrying capacity (anemia, CO poisoning, MetHb)	Cells cannot use O₂ (cyanide, severe sepsis)	Lung failure (ARDS, COPD)
PaO₂	↓	Normal	Normal	Normal	↓
SaO₂	↓	Normal	↓ (CO) / Normal (anemia)	Normal	↓
Hb	Normal	Normal	↓ (anemia)	Normal	Normal
2,3-DPG	↑ (adaptation)	Normal	↑	Normal	Variable
O₂ extraction	↑	↑ (chronic)	↑	↓ (cannot use O₂)	↑
Venous PO₂	↓	↓	↓	↑ (O₂ not consumed)	↓
Lactic acidosis	Late/severe	Early	With exertion	Early, severe	Late/severe
Treatment	Supplemental O₂, treat cause	Restore perfusion (inotropes, revascularization)	Transfusion, treat anemia, 100% O₂ for CO	Antidotes (hydroxocobalamin for CN⁻), supportive	O₂, mechanical ventilation

4. Types of Edema

Feature	Cardiac	Hepatic (Cirrhotic)	Renal (Nephrotic)	Renal (Nephritic)	Inflammatory	Lymphedema
Primary mechanism	↑Capillary hydrostatic pressure	↓Oncotic pressure + portal HTN	↓Oncotic pressure	Na/water retention	↑Capillary permeability	Impaired lymphatic drainage
Protein in fluid	Low (transudate)	Low (transudate)	Low (transudate)	Low/moderate	High (exudate)	High (protein-rich)
Distribution	Dependent (ankles, sacrum), ascites	Ascites predominant; peripheral edema	Periorbital (morning), generalized, ascites	Periorbital, generalized	Local (site of inflammation)	Unilateral limb (non-pitting)
Pitting	Yes	Yes	Yes	Yes	Yes (initially)	No (non-pitting - fibrotic)
Key lab finding	BNP ↑, ↑PCWP	↓Albumin, ↑PT, ↑bilirubin	Massive proteinuria >3.5g/day, ↓albumin	Hematuria, mild proteinuria, ↑creatinine	↑CRP, ↑WBC	Normal labs
RAAS activation	↑↑↑	↑↑	↑↑	↑↑	Local only	No
Key examples	Right heart failure, cor pulmonale	Alcoholic cirrhosis, viral hepatitis cirrhosis	Minimal change disease, membranous nephropathy	Post-streptococcal GN	Cellulitis, abscess	Filariasis, post-mastectomy

5. Types of Jaundice

Feature	Prehepatic (Hemolytic)	Hepatic (Hepatocellular)	Posthepatic (Obstructive)
Site of defect	RBC destruction (excessive bilirubin production)	Hepatocyte damage (conjugation + secretion failure)	Bile duct obstruction (secretion blocked)
Bilirubin type elevated	Unconjugated (indirect)	Both conjugated + unconjugated	Conjugated (direct)
Urine color	Normal (pale yellow)	Dark (urobilinogen + conjugated bili)	Dark (conjugated bilirubin - water soluble)
Stool color	Normal or dark	Pale	Pale / acholic (clay-colored)
Urine bilirubin	Negative (unconjugated not filtered)	Positive	Positive (conjugated is water-soluble)
Urinary urobilinogen	↑↑	↑ (early) / ↓ (late)	Absent
ALT / AST	Normal	↑↑↑	Normal or mildly ↑
ALP / GGT	Normal	Mildly ↑	↑↑↑
Pruritus	Absent	Variable	Present (bile salt deposition in skin)
Splenomegaly	Yes (hemolysis)	Yes (portal HTN in cirrhosis)	No
Examples	Sickle cell, hemolytic anemia, G6PD, transfusion reaction	Viral hepatitis, alcoholic hepatitis, cirrhosis, paracetamol toxicity	Gallstones (choledocholithiasis), pancreatic head cancer, cholangiocarcinoma, strictures

6. Types of Anemia

Feature	Iron Deficiency	B12 / Folate Deficiency	Hemolytic	Aplastic	Sickle Cell	Acute Blood Loss
MCV	↓ (microcytic)	↑ (macrocytic)	Normal or ↑	Normal	Normal	Normal
MCHC	↓ (hypochromic)	Normal	Normal	Normal	Normal	Normal
Reticulocytes	↓	↓	↑↑	↓↓	↑	↑ (day 7-10)
Serum iron	↓	Normal	↑ (hemolysis)	Normal	Normal	Normal
Ferritin	↓↓	Normal	↑	Normal	Normal	Normal
TIBC	↑↑	Normal	↓	Normal	Normal	Normal
Bilirubin (indirect)	Normal	Normal	↑↑	Normal	↑	Normal
LDH	Normal	↑ (ineffective erythropoiesis)	↑↑	Normal	↑	Normal
Bone marrow	Hyperplastic, ↓iron stores	Megaloblastic (giant precursors)	Hyperplastic	Hypocellular / fatty	Normal	Hyperplastic
Blood smear	Microcytic hypochromic, pencil cells	Macrocytes, hypersegmented neutrophils	Spherocytes / schistocytes	Pancytopenia	Sickle cells, target cells	Normal morphology
Key cause	Chronic blood loss, poor diet, malabsorption	Pernicious anemia, gastrectomy, veganism	Autoimmune, hereditary spherocytosis, G6PD	Drugs, autoimmune, radiation	HbS mutation (Glu→Val)	Trauma, GI bleed, obstetric
Neurological signs	Plummer-Vinson, pica, koilonychia	Subacute combined cord degeneration (B12 only)	None specific	None specific	Stroke (vaso-occlusion)	None

7. Heart Failure - Left vs. Right

Feature	Left Heart Failure	Right Heart Failure
Primary cause	MI, hypertension, aortic stenosis, dilated CMP	Left heart failure (most common!), pulmonary hypertension, COPD, pulmonary embolism, RV infarction
Backed-up circuit	Pulmonary venous congestion	Systemic venous congestion
Key symptoms	Dyspnea on exertion, orthopnea, PND, pink frothy sputum	Peripheral edema, weight gain, abdominal bloating
Key signs	Bilateral pulmonary rales, S3 gallop, displaced apex	JVD, hepatomegaly, pitting ankle edema, ascites, Kussmaul's sign
Hemodynamics	↑PCWP (pulmonary capillary wedge pressure)	↑CVP (central venous pressure), ↑JVP
CXR	Pulmonary vascular congestion, Kerley B lines, pleural effusions, "bat wing" edema	Cardiomegaly (RA/RV); pulmonary oligemia if cause is PE
BNP	↑↑	↑↑
Organ affected	Lungs	Liver (cardiac cirrhosis), kidneys (cardiorenal syndrome), gut (protein-losing enteropathy)

8. Acute vs. Chronic Inflammation

Feature	Acute Inflammation	Chronic Inflammation
Onset	Rapid (minutes-hours)	Slow (weeks-months-years)
Duration	Days to 2 weeks	Weeks to years
Predominant cell	Neutrophils	Macrophages, lymphocytes, plasma cells
Tissue response	Exudation, vascular changes dominant	Fibrosis + tissue destruction
Mediators	Histamine, bradykinin, PGE₂, C5a, LTB4	TNF-α, IL-1, IL-6, IFN-γ, TGF-β
Vascular changes	Prominent (vasodilation, ↑permeability)	Less prominent
Granuloma	No	Yes (granulomatous types: TB, sarcoidosis, Crohn's)
Outcome	Resolution, abscess, fibrosis, chronic inflammation	Fibrosis, scarring, systemic effects (amyloidosis)
Examples	Acute appendicitis, lobar pneumonia, acute gout	TB, Crohn's disease, RA, SLE, leprosy
Systemic effects	Fever, leukocytosis, ↑CRP, ↑ESR	Weight loss, anemia of chronic disease, amyloidosis

9. DKA vs. HHS (Hyperglycemic Comas)

Feature	Diabetic Ketoacidosis (DKA)	Hyperosmolar Hyperglycemic State (HHS)	Hypoglycemic Coma
DM type	Type 1 (mainly)	Type 2	Either (insulin excess)
Insulin	Absent	Relative deficiency (some present)	Excess
Blood glucose	>14 mmol/L (>250 mg/dL)	>33 mmol/L (>600 mg/dL)	<3.0 mmol/L
Ketones	↑↑↑ (positive urine/blood ketones)	Absent or trace	Absent
Osmolality	Mildly ↑ (~300-320)	↑↑↑ (>320 mOsm/kg)	Normal
pH	<7.35 (metabolic acidosis)	Normal (7.35-7.45)	Normal
Anion gap	↑↑ (>12)	Normal	Normal
Onset	Rapid (hours)	Slow (days-weeks)	Rapid (minutes)
Breathing	Kussmaul (deep, sighing)	Normal or rapid	Normal or rapid
Breath odor	Fruity (acetone)	Normal	Normal
Mortality	~1-5%	~15-20% (elderly, comorbidities)	Low if treated promptly
Treatment	Insulin IV + fluids + K⁺ replacement	Fluids (main) + insulin + anticoagulation	Glucose IV (50% dextrose) or glucagon IM

10. Respiratory Failure Types

Feature	Type I (Hypoxemic)	Type II (Hypercapnic/Ventilatory)
PaO₂	↓ (<60 mmHg)	↓
PaCO₂	Normal or ↓	↑ (>50 mmHg)
pH	Normal or ↑ (respiratory alkalosis)	↓ (respiratory acidosis)
Primary defect	Gas exchange failure (V/Q mismatch, shunt, diffusion)	Alveolar hypoventilation (pump failure)
A-a gradient	↑	Normal (pure hypoventilation)
Response to O₂	↑ if V/Q mismatch; poor if true shunt	↑ but may ↓drive in chronic COPD
Causes	ARDS, pneumonia, pulmonary edema, PE, pulmonary fibrosis	COPD exacerbation, asthma, GBS, myasthenia gravis, opioid overdose, obesity hypoventilation, flail chest
Treatment	High-flow O₂, treat underlying cause, mechanical ventilation	Non-invasive ventilation (BiPAP), mechanical ventilation; careful O₂ in COPD (avoid suppressing hypoxic drive)

11. Stages of Fever vs. Hyperthermia

Feature	Fever (Pyrexia)	Hyperthermia
Set-point	↑ (hypothalamic set-point raised)	Normal (heat-loss mechanisms overwhelmed)
Cause	Endogenous pyrogens (IL-1β, IL-6, TNF-α) → PGE₂	External heat, anticholinergics, uncouplers (DNP), neuroleptic malignant syndrome, malignant hyperthermia
Shivering in initiation	Yes (to raise T to new set-point)	No
Sweating	Only in defervescence stage	Absent (that is why dangerous)
Responds to antipyretics	Yes (NSAIDs/paracetamol block PGE₂)	No
Immune benefit	Yes (enhanced phagocyte/T cell function)	No
Dangerous T	>41°C (febrile convulsions, brain damage)	>40°C (rapidly life-threatening)
Treatment	Antipyretics (PGE₂ blockade), treat cause	Cooling blankets, ice packs, evaporative cooling, dantrolene (malignant hyperthermia)

12. Upper vs. Lower Motor Neuron Lesions

Feature	Upper Motor Neuron (UMN)	Lower Motor Neuron (LMN)
Location	Motor cortex, internal capsule, brainstem, corticospinal tract in spinal cord	Anterior horn cells, ventral root, peripheral nerve, NMJ
Muscle tone	↑ (spasticity) - "clasp-knife"	↓ (flaccidity)
Deep tendon reflexes	↑↑ (hyperreflexia)	↓ / absent (hyporeflexia)
Babinski sign	Positive (extensor plantar)	Negative
Muscle atrophy	Disuse atrophy (mild, late)	Denervation atrophy (severe, early)
Fasciculations	Absent	Present
Clonus	May be present	Absent
Affected distribution	Contralateral (brain), ipsilateral (if cord)	Same side, single nerve or root distribution
Examples	Stroke, MS, SCI (after spinal shock resolves), cerebral palsy	Polio, GBS, peripheral neuropathy, motor neuron disease (anterior horn)

13. Acute vs. Chronic Renal Failure

Feature	Acute Kidney Injury (AKI)	Chronic Kidney Disease (CKD)
Onset	Hours to days	Months to years
Reversibility	Often reversible (if treated early)	Irreversible (progressive)
Kidney size	Normal or enlarged	Small, shrunken (fibrosis) - except DM, ADPKD (enlarged)
Anemia	Absent (or mild dilutional)	Present (↓EPO production)
Bone disease	Absent	Renal osteodystrophy (secondary hyperparathyroidism)
Neuropathy	Absent	Uremic peripheral neuropathy
Creatinine	Rapidly rising	Gradually rising
Urine output	Oliguria common (ATN)	Often normal until late (isosthenuria - fixed SG 1.010)
Urine casts	Muddy brown (ATN), RBC casts (GN), WBC casts (pyelonephritis)	Broad waxy casts (CKD - reflect dilated tubules)
Key causes	Prerenal (volume depletion), ATN (ischemia/toxins), obstruction	DM nephropathy, hypertension, GN
Treatment goal	Identify and treat cause; supportive (dialysis if severe)	Slow progression; manage complications; RRT when ESKD

14. Primary vs. Secondary Hypertension

Feature	Primary (Essential)	Secondary
Frequency	~95% of cases	~5% of cases
Identifiable cause	No	Yes
Age of onset	Usually 30-60 years	Often younger (<30 or new onset in elderly)
Key mechanism	Polygenic + environmental (↑SNS, ↑RAAS, ↑Na retention, vascular remodeling)	Depends on cause (renal, endocrine, vascular)
Renin level	Normal or variable	↑ (renovascular, pheochromocytoma), ↓ (Conn's), variable
K⁺	Normal	↓ (Conn's - hyperaldosteronism), variable
Clues suggesting secondary	Resistant to treatment, young age, hypokalemia, episodic symptoms, abdominal bruit	Abdominal bruit (renovascular), episodic headache/sweating (pheo), adrenal mass
Top causes	—	Renal artery stenosis, primary hyperaldosteronism, pheochromocytoma, renal parenchymal disease, Cushing's
Treatment	Lifestyle + antihypertensives (ACEi/ARB, CCB, thiazide)	Treat underlying cause

These tables cover the core comparative mechanisms across the major topics in your exam. Each table highlights the key distinguishing features examiners typically test. Focus especially on shock types, hypersensitivity types, jaundice types, and anemia types - these are classic multi-choice and structured question favorites.

This is a shared conversation. Sign in to Orris to start your own chat.