• Effective osmolality (most important), effective vascular volume
• Common pathology
  • Any lung disease
  • Any CNS disease
  • Nausea and certain drugs
  • Certain cancers (e.g. oat cell Ca of the lung)
• Common drugs
  • Phenothiazines, anti-depressents (fluoxetine)

In cases of acute weight loss, use the equation (change in in Na x total body water) / Serum Na to determine expected water loss given no sodium gain. Compare to weight loss / 2.2. If patient lost less body water than expected, they must have retained Na.

Weight / 2.2 = Body water

(Change in Na X TBW)/Goal Na concentration

Change in Na x TBW

Urine NA > 20 mEq/l, serum urate <3.5 mg/dl, BUN <10 mg/dl and serum creatinine <1 mg/dl all suggest normal or increased effective vascular volume (SIADH)

The opposite values are seen in volume depletion states.

Inversely (for every 100 mg/dL increase in glucose, 1.6 mEq/L decrease in sodium)

1. Inappropriately dilute urine (osmolality under 700 mOsm/L in presence of hypernatremia) in the absemce of renal failure and loop diuretics
2. Typically, water intake is increased to match volume of water lossed
3. Give patient synthetic ADH (dDAVP)
   • Increase in urine osmalality indicates central DI
   • No change = nephrogenic

Since brain autocorrects for chronic osmolality change, rapid osmolality reduction will cause swelling, and rapid increase will cause brain dehydration and intracranial bleeds

Muscle has no compensatory mechanism

What is the most likely acid-base disorder based on the following conditions?

1. Low pH, low PCO₂
2. Low pH, high HCO₃
3. High pH, high PCO₂
4. High pH, low HCO₃

1. Metabolic acidosis, compensated by hyperventilation
2. Respiratory acidosis, compensated by production bicarbonate
3. Metabolic alkalosis, compensated by hypoventilation
4. Respiratory alkalosis, compensated by excretion of bicarbonate

1. Na - (Cl +HCO₃)
2. If AG is high, serum Cl is normal; if AG is normal, Cl is high.
3. Hypoalbuminemia, lithium intoxication, hyper-gammaglobulinemia, bromide intoxication (high Cl artifact)

1. Lactic acidosis, ketoacidosis, uremic acidosis, toxic acidosis
2. RTA, uremic acidosis (early), recovery stages of ketoacidosis, diarrhea, toluene

In patient with metabolic alkalosis and high urine anion gap, most likely vomit-induced

In patient with metabolic acidosis and reduced urine anion gap, most likely diarrhea-induced

1. Increased NADH
2. Can be induced by hypoxia, metformin, anti-retroviral drugs, diabetic ketoacidosis, all toxic alcohols
3. Severe carb. malabsorption --> colonic proliferation of d-LDH bacteria, which converts unabsorbed carbohydrate

1. Methanol: formic acid and lactic acid
2. Ethylene glycol: glycolic acid
3. Toluene: hippuric acid
4. Acetaminophen: pyroglutamic acid
5. Salicylate: ketoacids (probably lactic acids)

1. Intracellular shift P (urine P is low)
   • Alkaline pH
   • Carbohydrates
   • Insulin
2. Fecal loss of P (urine P is low)
3. Urinary loss of P (urine P is normal)

1. Ca reabsorption impaired by diminished Na reabsorption in loop of Henle; increased excretion
2. Do not directly affect Ca reabsorption; indirectly decreased by volume depletion
3. Decrease effective volume increases Na reabsorption in proximal tubule; calcium follows Na
4. Calcium reabsorption in proximal tubule decreased by NaCl infusion

A patient is given an unknown diuretic. After a week, you notice the following urine values:

1. Reduced calcium and increased Mg
2. Increased calcium and increased Mg
3. Slightly reduced calcium and slightly reduced Mg

For each case, what diuretic would you suspect?

1. Thiazide diuretic
2. Loop diuretic
3. K-sparing diuretics

1. An increase in blood pH by 0.1 unit increases protein-bound calcium by 0.17 mg/dL
2. An increase in albumin concentration by 1 g/dl increases protein-bound Ca by 0.8 mg%
3. An increase in globulin by 1 gm/dL increases protein-bound calcium by 0.18 mg/dl

• Ca (oxalate or phosphate), struvite, and cystine stones are radio-opaque stones.
• Uric acid stones are the only important radio-lucent stone.

• Mg²⁺, NH₄⁺, PO₄^3- 
• Urinary tract infection with urease-forming bacteria

Increase in urine pH; decrease in uric acid production

An increase in urine pH from 5.5 to above 6.5 would be more effictive in preventing UA stone formation than reducing the production of UA by 50.

Proximal tubular cell pH is inversely proportional to urine citrate reabsorption (and is directly proportional to excretion)

• Metabolic acidosis generally increases citrate reabsorption (decreases intracellular pH)
• K⁺ depletion increases citrate reabsorption
• Proximal RTA and type IV RTA does not cause hypcitraturia

• Hypercalciuria
• Hypocitraturia
• Hyperuricosuria
• Hyperoxaluria
• Urine pH abnormalities
• Urine infection

• Hight citrate
• High urine Mg
• Tamm-Hosfall protein
• Osteopontin

Hypertension with grade 3 or grade 4 retinopathy (exudates, hemorrhages, papilledema)

Severe hypertension --> renal vascular damage and narrowing --> renin-angiotensin system stimulated --> higher BP --> more renin vascular damage --> etc.

• Renal artery stenosis
  • Atherosclerosis
  • Fibromuscular dysplasia
• Primary hyperaldosteronism
• Renal parenchymal disease
• Hyperthyroidism/hypothyroidism
• Cushing's sydnrome
• Pheochromocytoma
• Contraceptive pills

No plasma renin increase in bilateral stenosis; hypertension is due to salt retention

In unilateral stenosis, high renin and renal salt retention both play a role in htn

• Primary hyperaldosteronism
• Increased non-aldosterone mineralocorticoids
• Licorics, carbenoxolone
• Low renin essential hypertension
• Liddle's syndrome (overexpression of ENaC), Gordon's syndrome (enhanced NaCl reabsorption at distal convoluted tubule), apparent mineralocorticoid excess state (ß-hydroxysteroid dehydrogenase defficiency)

1. Renal artery stenosis
2. Patients with htn treated with diuretic
3. Malignant htn
4. Renin producing tumor
5. Contraceptive pill use

• Captopril, enalapril, ramipril
• Prevent conversion of angiotensin I to angiotensin II, minimizing vasoconstriction, aldosterone secretion, while increasing vasodilators (bradykinin, NO, prostcyclin)
• Cough in 30%, angioedema, hyperkalemia

• DHPs
  
  • Amlodipine, nifedipine
  • Potent vasodilators
• Non-DHPs
  
  • Diltiazem, verapimil
  • Slow HR, reduce cardiac contraction, retard A-V nodal conduction
• Vasodilatory in nature (headaches, flushing, pedal edema), constipation

Lorsartan (Ang II receptor blocker), aliskerin (renin inhibitor)

Aliskerin can cause diarrhea

• Centrally acting alpha-agonists = methldopa, propanolol, clonidine  (drowsiness and dry-mouth)
• Alpha-adrenergic blocking agents = prazosin (first-dose hypotensive effect), terazosin, doxasin
• ß-adrenergic blockers = metoprolol (ß-1 selective), atenolol (ß-1 selective), labetolol (alpha and beta blocker), carvedilol (alpha and beta blocker), nebivolol (third generation ß-1 blocker)

Hydralazine (increases CO, HR, requiring concomitant ß-blocker and diuretic; headaches, tachycardia, lupus-like reaction)

Minoxidil (volume expansion, pericardial and serous effusions), also known Rogaine

Anyone with Stage 2⁺ or in Risk Group C

• Risk groups
  • Risk Group A = no risk factors or TOD/CCD (target organ disease, clinical cardiovascular disease)
  • Risk Group B = at least 1 risk factor, excluding DM, with no TOD/CCD
  • TOD/CCD and/or DM
• Stages
  • High normal = 130-139/85-89
  • Stage 1 = 140-159/90-99
  • Stage 2⁺ = >160/>100

• Atherosclerosis affecting the kidney, heart and brain (causing MI, stroke, renal artery stenosis)
• Smoking, dyslipidemia, diabetes mellitus, age > 60 yrs, men and post-menopausal women, family history of CV disease

• Vitamin D deficiency
• Electrolyte abnormalities (metabolic acidosis, hyperphophatemia, hypocalcemia, hyperkalemia, hypermagnesemia)
• Gynecomastia, hypogonadism, secondary hyperPTH
• High homocystein, high AGE, hyperlipidemia

1. Hemodialysis- requires dietary changes, risk of infection, constant visits to hospital
2. Peritoneal dialysis- allows more flexibility, risk of peritonitis
3. Renal transplantation- best survival statistics, but difficulty obtaining organ, requires immunosuppressive therapy, risk of transplant rejection

Chronic

(Note: large kidney seen in polycystic kidney disease and amyloidosis)

Children = liquid nephrosis

Adult = focal segmental glomerular sclerosis and membranous nephropathy

RBCs = glomerular pathology

WBCs = tubulointerstitial inflammation

Produced at constant rate by all nucleated cells and filtered freely at glomerulus; completely reabsorbed and broken down in proximal tubule

Serum levels reflect GFR better than creatinine, but test is too expensive

H+ ions of the acid are buffered by HCO₃^-, which is counterbalanced by anions of acid (example, toxic acidosis, renal failure, lactic acidosis)

In normal Ag, chloride is increased to counterbalance loss of buffered bicarb (hypercholeremic acidosis). Examples include diarrhea and the RTA's