CASE HISTORY-1 — 25-year-old married woman, regular menstruation

CASE HISTORY-2 — Patient with weakness, truncal fat, thin limbs, abdominal striae, poor wound healing

• Thin arms and legs (muscle wasting from proteolysis by excess cortisol)
• Full abdomen, back, and face (truncal/central obesity, "moon face," "buffalo hump")
• Reddish/purple striae on the abdomen (due to skin thinning and rupture of dermal collagen)
• Poor wound healing

1. Inhibits fibroblast proliferation and collagen synthesis
2. Has anti-inflammatory and immunosuppressive effects (suppresses growth factors needed for healing)
3. Increases protein catabolism, reducing availability of amino acids for tissue repair

• Cortisol stimulates gluconeogenesis in the liver (promotes hepatic glucose output)
• Cortisol induces insulin resistance in peripheral tissues (muscle and fat)
• Cortisol promotes proteolysis in muscle, releasing amino acids as gluconeogenic substrates
• Cortisol promotes lipolysis, releasing glycerol as gluconeogenic substrate
• Net result: raised fasting and postprandial blood glucose levels

CASE HISTORY-3 — 69-year-old man, tremors, mask face, monotonous speech, bradykinesia, rigidity, no intellectual deficit

• Dopamine normally facilitates movement initiation via the direct pathway (D1 receptors) and inhibits the indirect pathway (D2 receptors)
• With dopamine deficiency, the indirect pathway (which inhibits movement) becomes overactive
• This leads to excessive inhibition of the thalamus and motor cortex
• Result: reduced voluntary movement output (bradykinesia = slowness), akinesia (poverty of movement), and rigidity (constant high muscle tone from disrupted reciprocal inhibition)
• Resting tremor arises from oscillatory activity in thalamic circuits no longer properly regulated

• Levodopa (L-DOPA) + Carbidopa - the cornerstone of therapy. Levodopa crosses the blood-brain barrier and is converted to dopamine in the substantia nigra. Carbidopa is a peripheral decarboxylase inhibitor that prevents peripheral conversion of levodopa, reducing side effects and increasing CNS availability.
• Dopamine agonists - pramipexole, ropinirole (adjuvant or as initial therapy in younger patients)
• MAO-B inhibitors - selegiline, rasagiline (slow dopamine breakdown)
• Anticholinergics - benztropine (reduce tremor)
• Deep Brain Stimulation (DBS) - for advanced disease refractory to medications

CASE HISTORY-4 — Young female, ptosis, muscle weakness worse in evenings, chewing/swallowing/speaking weakness, responds to neostigmine

• Block the receptor binding site for ACh
• Cause complement-mediated destruction of the postsynaptic membrane
• Accelerate receptor internalization and degradation

• Increases the concentration and prolongs the duration of ACh at the NMJ
• Allows the limited number of remaining functional receptors to be stimulated more effectively
• Repeated binding of ACh molecules to available receptors restores sufficient neuromuscular transmission to improve muscle strength

CASE HISTORY-5 — 28-year-old female, nervousness, sweating, palpitation, amenorrhea, tachycardia, lid retraction, fine tremors, BMR +40%, cholesterol 100 mg%, pulse 120/min

• BMR +40%: Significantly elevated (normal: -10% to +10%). Indicates markedly increased metabolic rate. Values above +20% are considered abnormal; +40% is strongly suggestive of thyrotoxicosis.
• Serum cholesterol 100 mg%: Low (normal: ~150-200 mg%). Thyroid hormones stimulate LDL receptor upregulation and accelerate cholesterol catabolism, causing hypocholesterolemia in hyperthyroidism.
• Basal pulse rate 120/min: Tachycardia (normal: 60-100/min). Thyroid hormones increase cardiac sensitivity to catecholamines and directly stimulate the heart.

• Heat intolerance, sweating, nervousness, restlessness (hypermetabolism)
• Weight loss despite increased appetite
• Tachycardia, cardiac enlargement, extra systoles, dyspnea on exertion
• Fine resting tremors of outstretched hands
• Amenorrhea (excess thyroid hormones disrupt the HPG axis)
• Lid retraction and skin/lid changes

1. Serum T3 and T4 (Free T4, Free T3) - will be elevated
2. TSH (Thyroid Stimulating Hormone) - will be suppressed (low/undetectable) in primary hyperthyroidism
3. TSH receptor antibodies (TRAb / TSI) - positive in Graves' disease (confirms autoimmune etiology)
4. Radioactive Iodine Uptake (RAIU) scan - diffusely increased uptake in Graves'; focal uptake in toxic nodule
5. Thyroid ultrasound - assess gland size, vascularity, nodules

CASE HISTORY-6 — Excessive drinking, colorless urine, polyuria, polydipsia, markedly dehydrated when water withheld; urine specific gravity 1002-1004, no sugar/blood/albumin

• Central (Neurogenic) DI: Deficiency of ADH (Antidiuretic Hormone/Arginine Vasopressin) from the posterior pituitary due to damage/destruction of hypothalamic nuclei (supraoptic/paraventricular) or pituitary stalk - from tumors, trauma, surgery, inflammation (sarcoidosis), or idiopathic
• Nephrogenic DI: Kidney tubules are unresponsive to ADH (genetic mutation of V2 receptor or AQP2 channels, lithium toxicity, hypercalcemia)

1. Diabetes Mellitus - osmotic diuresis from glycosuria
2. Primary Polydipsia (Psychogenic) - compulsive water drinking; ADH is suppressed secondarily
3. Chronic renal failure - loss of concentrating ability
4. Hypercalcemia - inhibits ADH action at tubules
5. Hypokalemia - also impairs tubular response to ADH
6. Diuretic use (pharmacological)

• Central DI: Desmopressin (DDAVP) - synthetic ADH analogue, given intranasally, orally, or SC. Ensure adequate fluid intake.
• Nephrogenic DI: Low sodium/low protein diet, thiazide diuretics (paradoxically reduce urine volume by causing mild volume depletion and increasing proximal tubular reabsorption), NSAIDs (indomethacin), correct underlying cause (stop lithium, treat hypercalcemia)
• Identify and treat underlying cause (e.g., surgical removal of craniopharyngioma)

CASE HISTORY-7 — 3-year-old male child, persistent bleeding from multiple sites, joint swelling, coagulation time prolonged, bleeding time and prothrombin time normal, male relatives affected

• Males affected (X-linked recessive; males are hemizygous and manifest disease)
• Prolonged coagulation time (APTT) - reflects intrinsic pathway defect
• Normal bleeding time - platelet function is intact (primary hemostasis normal)
• Normal prothrombin time (PT) - extrinsic pathway (Factor VII) is normal
• Hemarthrosis (joint bleeding with swelling + fever) - classic in hemophilia
• Family history in male relatives

• If one X chromosome carries the mutant allele, the other normal X chromosome provides sufficient Factor VIII for normal coagulation
• Therefore females are typically carriers (one normal + one mutant X) but asymptomatic, as even 50% Factor VIII activity is adequate
• Only in rare cases (homozygous females, or Turner syndrome XO) do females manifest the disease
• Males (XY) have only one X chromosome - if it carries the mutant gene, they have no backup and manifest full disease

• Recombinant Factor VIII concentrate (preferred) - infused intravenously to restore clotting factor levels and allow the coagulation cascade to proceed normally
• Fresh Frozen Plasma (FFP) or Cryoprecipitate - contain Factor VIII; used when concentrates are unavailable
• Desmopressin (DDAVP) - in mild hemophilia A; stimulates release of stored Factor VIII from endothelial cells
• Inhibitor management with bypassing agents (Factor VIIa/aPCC) if antibodies to Factor VIII develop

CASE HISTORY-8 — Yellow discoloration of sclera and skin, pale clay-colored stools, itching, loss of appetite; Stool: stercobilinogen absent; Urine: bilirubin present; Blood: serum bilirubin 6 mg/100ml (direct); Liver enzymes elevated; Van den Bergh test: direct positive

• No bile salts enter the gut → impaired fat emulsification → fat malabsorption (steatorrhea)
• Unabsorbed fat is excreted in stools → pale/clay-colored (no stercobilin since conjugated bilirubin cannot enter gut), bulky, and foul-smelling (fatty, putrid stools)
• The pale/clay color is because stercobilin (formed from bilirubin by gut bacteria) is absent - as confirmed by absent stercobilinogen in stool

• Direct bilirubin = conjugated bilirubin (water-soluble, glucuronidated in the liver)
• In obstructive jaundice, conjugated bilirubin is produced normally by the liver but cannot be excreted into bile due to the obstruction
• It backs up into the blood (regurgitation jaundice), causing elevated direct (conjugated) bilirubin in serum
• Conjugated bilirubin reacts directly with the diazo reagent without needing alcohol → direct positive reaction
• It is water-soluble → excreted in urine (bilirubinuria, dark urine) - confirmed by bilirubin present in urine

CASE HISTORY-9 — Pulmonary function tests of two patients

• FEV1/FVC = 84% - normal/elevated (≥70-80% is normal; >80% is characteristic of restriction)
• FVC is reduced (2.5 L - reduced due to stiff, non-compliant lungs with reduced total lung capacity)
• FEV1 is proportionally reduced
• Low PEFR (200 L/min) due to small lung volumes
• Lymphocytosis on blood smear suggests a possible viral/granulomatous/autoimmune etiology (e.g., hypersensitivity pneumonitis, sarcoidosis, viral interstitial pneumonia)

• FEV1/FVC = 66% - reduced (diagnostic cut-off: <70%)
• FVC is relatively preserved (3.0 L) or may be reduced due to air trapping
• FEV1 disproportionately reduced due to airway obstruction slowing expiration
• Low PEFR (100 L/min) due to airway narrowing
• Eosinophilia on blood smear strongly suggests asthma (allergic/atopic obstructive disease)

• Caused by inadequate oxygenation of blood in the lungs
• In Patient A (restrictive): thickened alveolar-capillary membrane impairs gas diffusion; reduced lung volume means less surface area for O2 exchange
• In Patient B (obstructive): airway narrowing causes air trapping, ventilation-perfusion (V/Q) mismatch, and reduced alveolar ventilation → reduced PAO2 → reduced PaO2

CASE HISTORY-10 — 15-year-old female, sudden fever (102°F), abdominal pain, vomiting, tachycardia (100/min), BP 110/70, RR 20/min, TLC 30,000/c.mm, neutrophils 90%, appendicectomy scheduled

• The acute bacterial infection/inflammation in the appendix releases inflammatory mediators (IL-1, IL-6, TNF-α, G-CSF)
• These stimulate the bone marrow to rapidly produce and release neutrophils
• There is also marginated pool mobilization - neutrophils adhering to vessel walls are released into circulation
• Endotoxins and bacterial products directly stimulate neutrophil release
• This is an appropriate acute-phase response to bacterial inflammation - neutrophils are the first line of cellular defense, migrating to the site of infection for phagocytosis