Additional information

1. Complement levels in glomerular diseases

Normal serum complement

PAN*, Granulomatosis with polyangiitis (GPA), hypersensitivity vasculitis, Henoch-Schonlein purpura, Goodpasture’s syndrome, IgA or IgG nephropathy, Anti GBM disease

Low serum complement

Acute post-streptococcal glomerulonephritis and HUS (both show a low C3, normal C4), membranoproliferative glomerulonephritis, SABE**, cryoglobulinemia (low C4, normal C3), SLE

*PAN polyarteritis nodosa

**SABE subacute bacterial endocarditis

2. Drugs associated with glomerular diseases

Conditions	Associated drugs
Minimal change disease	NSAIDS, Interferons
Membranous glomerulonephritis	NSAIDS, Penicillamine, mercury
Focal segmental glomerulosclerosis	Heroin, pamidronate
HUS	Cyclosporine, tacrolimus, OC pills, mitomycin C

3. Azotemia: It is characterized by elevated levels of nitrogenous compounds such as creatinine and BUN in the blood. It is seen in prerenal, intrinsic renal and postrenal causes like hypotension, obstructive uropathy, glomerulonephritis etc.

   Uremia: It is the elevation of blood urea levels. Azotemia can progress to uremia. Uremia is clinically symptomatic and presents with anorexia, nausea, vomiting, edema, change in the level of consciousness etc. It is seen in ESRD.

Indications for dialysis in AKI

• Refractory hyperkalemia
• Refractory volume overload, pulmonary edema
• Uremic pericarditis
• Uremic pleuritis
• Intractable acidosis
• Lithium or ethylene glycol poisoning
• Uremic encephalopathy

5. Types of radiopaque and radiolucent stones

Radiopaque

• Calcium oxalate
• Calcium phosphate
• Calcium carbonate
• Struvite

Radiolucent

• Uric acid
• Cystine

• Calcium phosphate and struvite stones are formed in alkaline urine; seen after acetazolamide intake due to increased urine calcium and pH; distal RTA shows calcium phosphate stones
• Calcium oxalate, uric acid and cystine stones are formed in acidic urine.
• Increased urinary calcium predisposes to calcium stones and is seen in increased salt intake, low or high vitamin D levels, increased diet acid load such as cheese, meats, diary etc.
• Antibiotics can increase formation of calcium oxalate stones by increasing oxalate levels in the gut.
• Uric acid stones may be seen in metabolic syndrome, gout, diabetes, obesity, high protein diet, myeloproliferative disorders, diarrhea, probenecid

Paraneoplastic syndrome associated with RCC

• Polycythemia from erythropoietin production
• Hypercalcemia from PTH production
• Hypertension from renin production
• Cushing’s syndrome from glucocorticoid production
• Feminization or masculinization from gonadotropin production

8. Simple renal cysts: They are fluid-filled cysts that are seen in one or both kidneys. They may be single or multiple. They are benign and do not interfere with renal function. They may range in size from a pea to golf ball. They are quite common especially over the age of 50 years. Most simple cysts are diagnosed on imaging for other purposes. Some cases may present with abdominal or back discomfort, urinary retention, UTI, fever, hypertension and hematuria. Asymptomatic cysts do not need treatment. They are monitored by serial ultrasound. Symptomatic cysts can be drained by sclerotherapy with alcohol or removed by surgery.

9. Hydronephrosis is the dilation of renal pelvis and calyces with urine due to obstruction to the outflow of urine. It may be unilateral or bilateral. Congenital PUJ (pelvi-ureteric junction) obstruction is the most common cause of hydronephrosis in the neonatal period.

   Causes of hydronephrosis

Unilateral hydronephrosis

• Calculi in ureter or renal pelvis
• PUJ obstruction shows unilateral hydronephrosis without hydroureter
• Unilateral hydronephrosis with hydroureter may be seen in ureterovesical junction obstruction
• VUR
• Ureteral fibrosis
• Trauma to ureter
• Extrinsic ureteral obstruction from cancer cervix, colon, prostate, rectum or cecum.
• Retroperitoneal fibrosis

Bilateral hydronephrosis

• All causes of unilateral obstruction involving both sides at the same time
• Posterior urethral valves
• VUR
• Bladder neck stenosis
• Urethral stricture
• Cancer prostate
• BPH

Indications for retrograde urethrography and cystography in trauma patients

• Blood at the urethral meatus
• Gross hematuria after pelvic trauma
• High-riding or freely mobile prostate
• Pelvic hematoma
• Displaced fracture of the pubic rami
• Butterfly-pattern of perineal bruising, scrotal or penile hematoma

Criteria for the diagnosis of gestational diabetes*

Cut-off values following oral glucose tolerance test with 75 gm glucose

• Fasting >= 92 mg/dl
• 1 hour >= 180 mg/dl
• 2 hours >= 153 mg/dl

* Screening for GDM is done at 24-28 weeks of gestation.

12. Hypoglycemia (insulin shock): It is low blood glucose, typically < 70 mg/dl. Some people may develop symptoms at blood glucose levels higher than 70 mg/dl while some, especially diabetics,may be asymptomatic even with lower levels. It presents with jitteriness, sweating, headache, tiredness, dizziness, palor, confusion, irregular heart rate and seizures or loss of consciousness in extreme cases. Most people recover with oral glucose tablets, sugar, candy, fruit juice etc. Some cases may need glucagon.

Causes of hypoglycemia

• Insulin and antidiabetic medications
• Insulinoma
• Postprandial or reactive hypoglycemia, seen in gastric bypass due to excess insulin secretion
• Quinine, pentamidine
• Growth hormone deficiency
• Chronic liver and/or kidney disease
• Glycogen storage disorders
• Surreptitious use of Insulin (C peptide will be low or undetectable but insulin levels will be elevated), factitious disorder or Munchausen syndrome

13. Differentials for common neck masses

Acute

• Sialadenitis: local edema, pain, erythema, seen in dehydration, following dental procedures
• Lymphadenopathy from CMV, EBV, toxoplasmosis, viral URTI, Bartonella henselae, HIV, tuberculosis (fixed, firm nodes); Staphylococcal and Streptococcal infections
• Hematoma: follows trauma, monitor if small, surgery if large or expanding
• Pseudoaneurysm or AV fistula: soft, pulsatile mass, thrill or bruit

Subacute

• Squamous cell carcinoma of upper GIT and upper respiratory tract (HPV, oral sex, smoking, alcoholism, betel nut chewers, non-healing ulcers)
• Amyloidosis
• Lymphoma (painless, enlarging node)
• Metastases (melanoma, lung, breast, colon, genitourinary cancers), matted, fixed nodes
• Parotid masses (slow growing, VII nerve involvement)
• Sjogren syndrome
• Sarcoidosis
• Chronic sialadenitis: pain after meals

Chronic

• Goitre: Grave’s disease, Hashimoto’s thyroiditis, iodine deficiency, lithium toxicity, toxic multinodular goitre
• Thyroid nodule: solitary benign nodules, thyroid cancer, toxic adenoma
• Thyroglossal duct cyst: in children, slow growing, more prominent after URTI, midline, close to hyoid bone, moves with swallowing, evaluate with CT , treat with antibiotics and excision (Sistrunk procedure)
• Branchial cleft cyst: in children, below angle of mandible, anterior to sternocleidomastoid; prominent after URTI, treat with antibiotics and excision
• Dermoid cyst: in children and young adults, submental triangle, soft, doughy mass, treat by excision
• Carotid body tumor: upper neck, pulsatile, hypertension, flushing, bruit or thrill
• Glomus jugulare tumors: similar to carotid body tumors
• Lipoma: soft, mobile, monitor or elective excision
• Laryngocele: midline, above thyroid cartilage, sensation of lump in throat; caused by repetitive blowing into a musical instrument, coughing.
• Parathyroid masses: located in anterior cervical triangle, monitor PTH and serum calcium

14. Euthyroid sick syndrome: It involves the presence of abnormal thyroid function tests in the absence of thyroid disorders. It shows increased reverse T3, low T3, TSH and T4 are variable. It is seen in various disorders of the gastrointestinal, pulmonary, renal, cardiovascular and metabolic disorders and in sepsis, burns, trauma, starvation and malignancy. Thyroid function returns back to normal on recovery from the underlying condition.
15. Untreated hypothyroidism during pregnancy is associated with miscarriages, preterm delivery, fetal death, PPH and mental retardation in newborns.
16. Cretinism: It is untreated congenital hypothyroidism. Causes include thyroid gland dysgenesis, iodine deficient diet (endemic cretinism), defects in thyroid hormone synthesis and transplacental passage of maternal blocking antibodies in autoimmune thyroiditis. It presents with delayed milestones, mental retardation, goitre and failure to thrive. Treatment with oral thyroxine should be started immediately (within the first 15 days of life) to preserve neurological function.
17. Amiodarone can cause type 1 thyrotoxicosis due to high iodine content of the drug, or it may cause type 2 thyrotoxicosis from damage to the thyroid gland with release of thyroid hormones. Type 1 results in increased production and release of thyroid hormones while type 2 causes increased release of preformed thyroid hormone. Drugs like interferon alpha, lithium, interleukin 2 also cause type 2 thyrotoxicosis. Type 1 is treated with antithyroid drugs like PTU and methimazole with potassium perchlorate which inhibits the uptake of iodine by the sodium-iodide symporter or NIS. Type 2 is treated with glucocorticoids.
18. Estrogen increases thyroid binding globulin. As a result, in pregnancy and estrogen therapy, total T4 and T3 will rise while TSH and free T4 will remain normal. As free hormone levels do not rise it does not cause hyperthyroidism. Androgens, cirrhosis and protein malnutrition decrease thyroid binding globulin (TBG) levels. The amount of TBG can be estimated by T3 resin uptake. Higher the value of resin uptake lower is the TBG level and vice versa.
19. Dopamine and glucocorticoids decrease TSH while total T4, total T3 and free T4 remain the same.
20. Thyroid storm: It is a life threatening event seen in patients of hyperthyroidism following non-compliance or discontinuation of antithyroid medications combined with infections, stresses like surgery, acute illness, trauma and pregnancy. It presents with hyperthermia, delirium, altered sensorium, seizures, coma, diarrhea, nausea, vomiting, jaundice, tachycardia, CCF and atrial fibrillation. Treatment is multi pronged with PTU (preferred) or methimazole, inorganic iodine, cholestyramine, propranolol, intravenous hydrocortisone or dexamethasone, oral prednisone; paracetamol and managing the precipitating illness. Plasmapheresis helps in severe cases. Diltiazem can be used as a substitute to beta blockers in patients with contraindications to beta blocker therapy like asthma.

Roles of drugs used to treat thyroid storm

Drug	Role
PTU and methimazole	Block the synthesis of thyroid hormones, PTU also blocks the peripheral conversion of T4 to T3
Inorganic iodine, potassium iodide	Decreases release of preformed T4 and T3; given 1 hour after antithyroid drugs as iodine can increase hormone production;
Beta blockers oral or iv (propranolol preferred)	Control peripheral effects of thyroid hormones like tachycardia; decrease T4 to T3 conversion
Glucocorticoids	Decrease the peripheral conversion of T4 to T3, to manage accompanying adrenal insufficiency
Cholestyramine	Decreases enterohepatic circulation of thyroid hormones, decreases serum levels, increases excretion in stool

21. Familial hypocalciuric hypercalcemia: It is an inherited, AD disorder caused by mutation in the calcium sensing receptor which causes the receptor to become insensitive to serum calcium levels. This interferes with feedback inhibition of PTH secretion resulting in hyperparathyroidism. Laboratory findings include hypercalcemia and calcium/creatinine ratio is < 0.01. Most patients are asymptomatic, some may present with fatigue, weakness, excessive thirst, constipation, low concentration, chondrocalcinosis and pancreatitis. No treatment is needed. Patients are at increased risk of MEN I.
22. Causes of hypercalcemia with increased PTH include primary and tertiary hyperparathyroidism, lithium induced hypercalcemia and familial hypocalciuric hypercalcemia.
23. Causes of hypercalcemia and hypocalcemia

Hypercalcemia

• Hyperparathyroidism
• Malignancy induced hypercalcemia
• Paraneoplastic syndromes due to excess PTHrP
• MEN 1
• Familial hypocalciuric hypercalcemia
• Sarcoidosis, tuberculosis
• AIDS
• Williams syndrome
• Drugs like thiazides,lithium, Vit D,A, aluminium toxicity, milkalklai syndrome, estrogens, theophylline
• Immobilization

Hypocalcemia

• Hypoparathyroidism

• Vit D deficiency or receptor defects

• Renal failure, chronic kidney disease

• Chronic liver disease

• Hungry bone syndrome

• Malnutrition

• Pseudohypothyroidism

• Hypomagnesemia and hypermagnesemia

• Massive blood transfusion with citrated blood

• Pancreatitis

• Hyperphosphatemia

• Osteomalacia

• Drugs like imatinib, bisphosphonates, calcitonin, denosumab

  Malignancy-induced hypercalcemia is usually associated with a low PTH but possibly a high PTHrP.

24. Autoimmune polyendocrinopathy syndrome: It is an autoimmune condition characterized by adrenal insufficiency, chronic mucocutaneous candidiasis, hypoparathyroidism, hypoplasia of the dental enamel and nail dystrophy, type 1 DM, Hashimoto’s thyroiditis or Grave’s disease, celiac disease, myasthenia gravis, atrophic gastritis and pernicious anemia.