Renal Endocrine Review

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Hyperpigmentation, Hyponatremia, Hyperkalemia, lymphocytosis, eosinophilia, hypoglycemia.: Addison's Disease/Acute adrenal crisis
High levels of VLCFA, behavior problems emotional lability, visual and gait disturbances, adrenal insufficiency.: Adrenoleukodystrophy
Causes of adrenal insufficiency (12): ketoconazole, suramin, metastatic tumor, fungal infection, adrenal hemorrhage, tuberculosis, adrenoleukodystrophy, Familial glucocorticoid deficiency, Addison's disease, HIV, CAH
Glucocorticoid Receptor Agonists: Cortisol, synthetic glucocorticoids, aldosterone
Glucocorticoid Receptor Antagonists/partial agonists: 11-deoxycortisol, DOC, testosterone, and 17-beta-estradiol, MIFEPRISTONE (RU486)
Hormones synthesized in the zona glomerulosa of the adrenal gland: Aldosterone. NOT cortisol or androgens (lacks 17-alpha-hydroxylase)
Hormones synthesized in the zona fasciculata of the adrenal gland: Cortisol and androgens. NOT aldosterone (lacks CYP11B2)
Hormones synthesized in the zona reticularis of the adrenal gland: Cortisol and androgens. NOT aldosterone. (lacks CYP11B2)
Androgen hormones: DHEA, DHEA sulfate, androstenedione
Mechanism of ACTH action on cells: Binds PM receptor - activates Gs - Adenylate cyclase - cAMP - pKA - phosphorylates cholesterol ester hydrolase
Rate-limiting step of cholesterol conversion to steroid hormones: Cholesterol - pregnenolone. Occurs in the mitochondria, and is increased by ACTH. Enzyme is cholesterol desmolase (CYP11A1). Through StAR.
Key enzyme in making Aldosterone: CYP11B2 (P450aldo/aldosterone synthase)
Symptoms of Glucocorticoid deficiency: weakness, fatigue, anorexia, nausea, vomiting, hypotension, hyponatremia, hypoglycemia, hyperpigmentation
Symptoms of Mineralcorticoid deficiency: Hyponatremia, hyperkalemia, dehydration, hypotension, acidosis, hyperpigmentation, weakness, fatigue. Lab: normocytic, normochromic anemia, neutropenia, eosinophilia, lymphocytosis, azotemia with increased BUN and serum creatinine.
Tumors causing ectopic ACTH syndrome: small cell lung carcinoma, pancreatic islet cell tumor, carcinoid tumor, medullary carcinoma of thyroid, pheochromocytoma
Clinical features of Cushing's syndrome: obesity, HTN, plethora, hirsutism, striae, acne, osteopenia, emotional lability, depression, amenorrhea, impotence, glucose intolerance, hyperlipidemia.
hypertension and hypokalemia: Adrenal Adenoma
Causes of secondary hypertension: OSA, aldosteronism, renal artery stenosis, renal parenchymal disease, Cushing's syndrome, coarctation of the aorta, high catecholamines, pheochromocytoma, estrogens, MAOI, erythropoietin, hyperparathyroidism, high growth hormone, hyper- or hypothyroidism, high salt intake, alcohol, obesity.
symptoms of hypokalemia: myalgia, muscle weakness, polyuria, dysrhythmia, rhabdomyolysis
Path of circulation through the kidney: aorta - renal artery - segmental (lobar) artery - interlobar - arcuate - interlobular - afferent arteriole - glomerulus - efferent arteriole - peritubular cap and vasa recta - interlobular vein - arcuate vein - interlobar - segmental - renal ven - IVC
cell types of the anterior pituitary: acidophils (pale pink) = somatotropes, lactotropes.
basophils (deep pink) = corticotropes, thyrotropes, gonadotropes.
Cromophobes (poor stain) = quiescent?
Hormones released by the anterior pituitary: GH, FSH, LH, TSH, ACTH, PRL
Hormones released by the posterior pituitary: ADH, oxytocin
Cell type that produces calcitonin: parafollicular (clear) cells of the thyroid
2 cell types of the parathyroid: Chief cells (release PTH), and oxyphil cells
cell type derived from the ultimobranchial body of the 4th pharyngeal pouch: C cells of the thyroid
structures derived from the 3rd and 4th pharyngeal pouches: parathyroid glands
Structure derived from the 3rd pharyngeal pouch: thymus
structure derived from floor of pharynx between 1st and 2nd pharyngeal arches: thyroid
Muscles and nerves derived from 1st pharyngeal arch (mandibular): CN V, muscles of mastication, mylohyoid, ant. belly of digastric, tensor typmpani, tensor veli palatini
Muscles and nerves derived from 2nd pharyngeal arch (hyoid): CN VII, muscles of facial expression, stapedius, stylohyoid, post. belly of digastric
Muscles and nerves derived from the 3rd pharyngeal arch: CN IX, stylopharyngeus
Muscles and nerves derived from the 4th and 6th pharyngeal arch: CN X, cricothyroid, levator veli palatini, constrictors of pharynx, intrinsic muscles of larynx, striated muscles of esophagus
Hormones released from the adrenal medulla: epinephrine and NE
Hormones released from the zona glomerulosa of the adrenal cortex: mineralocorticoids (aldosterone)
Hormones released from the zona fasciculata of the adrenal cortex: Glucocorticoids (cortisol)
Hormones released from the zona reticularis of the adrenal cortex: Androgens (testosterone)
Hormone released by the pineal gland: melatonin (released by chief cells of pineal)
Venous drainage of adrenal glands: Right adrenal: directly to vena cava.
Left adrenal: Branch to Left Renal Vein.
Enzyme deficient in Congenital Adrenal Hyperplasia: 21-Hydroxylase Deficiency
Forms of adrenal insufficiency: 1) primary - Addison's Dz
2) secondary - pituitary tumor
3) tertiary - exogenous glucocorticoids
Symptoms of primary adrenal insufficiency (Addison's Dz): fatigue, NVD, hypotension, hyponatremia, hyperkalemia, acidosis, hypoglycemia, azotemia, hypercalcemia, hyperpigmentation, salt craving, sexual dysfunction, menstrual abnormalities, arthralgia, myalgia
features of secondary or tertiary adrenal insufficiency: mineralcorticoid activity intact (renin-AgII), no hyperpigmentation.
Test with metyrapone or insulin tolerance test
Test for primary adrenal insufficiency: cosyntropin stimulation
Test for secondary adrenal insufficiency: Metyrapone test
2 things required for diagnosis of Cushing's Syndrome: 1) Clinical stigmata of hypercortisolism.
2) Biochemical hypercortisolism.
Sreening tests for Cushing's syndrome: overnight low dose dexamethasone suppresion test, 24-hour urine free cortisol, midnight serum or salivary cortisol levels
Test to distinguish pituitary tumor vs. ectopic source of ACTH: petrosal sinus levels of ACTH
symptoms of pheochromocytoma: hypertension, tachycardia, palpitations, pallor, sweating, headaches, orthostatic hypotension, constipation, flushing, nervousness, tremor, weight loss.
Primary Hyperaldosteronism: hypertension, hypokalemia, metabolic alkalosis, feedback through RAS, inappropriate kaluresis, sensitive to salt intake, volume, posture, serum potassium
Substance used to measure total body water: tritium or deuterium
Substance used to measure extracellular water: inulin or mannitol
Measurement of intracellular water: calculated from TBW - ECW
Substance used to measure plasma water: Evan's blue or radioactive albumin
Measurement of interstitial water: Calculated from ECW - Plasma water
Hyperosmotic volume expansion: More salt than water is ingested. ECF volume increases. Osmolality increases.
Isoosmotic volume expansion: Intake of isoosmotic solution. Increases ECF volume. Osmolality remains the same.
Hypoosmotic volume expansion: Intake of pure water. Increased volume of both ICF and ECF, decreased osmolality.
Estimate of plasma osmolality: 2 x Plasma Na+ concentration
Calculation of plasma osmolality: 2 x P[Na+] + [glucose]/18 + BUN/3
Effect of renal sympathetic nerve activation (by fall in BP - sensed by baroreceptor): Decreased Na+ excretion, Increased ECFV
Effect of activation of RAS (by fall in BP - sensed by baroreceptor): Decreased Na+ excretion, Increased ECFV
Effect of activating ADH (sensed by osmoreceptor): Decreased water excretion, decreased plasma osmolality, increased TBW.
Effect of activating atrial natriuretic peptide (atrial stretch - sensed by increased ECW): Increased Na+ excretion, decreased ECFV
Control of renin release from juxtaglomerular cells (3 ways): 1) decreased NaCl sensed by macula densa.
2) Increased cAMP by activation of beta1-adrenoceptors or PGE2/PGI2
3) Increased Intracellular Ca2+ (stretch of arteriolar cells)inhibits renin secretion
Actions of angiotensin II: increases sodium and water retention, constricts glomerular arterioles, constricts systemic arteries and increases BP, augments NE release/sympathetic activity, stimulates thirst in hypothalamus, simulates ADH (hypothalamus), stimulates zona glomerulosa release of aldosterone.
Action of aldosterone: Na+ resorption in distal tubule (increase of Na+/K+ ATPase and increase of luminal Na+ permeability)
Action of ADH: 1) Causes water resorption in the collecting duct
2) increases urea resorption in the collecting duct
Action of endothelin: Acts on ETA and ETB receptors to constrict cortical arteries and inhibit Na+ resorption in the distal tubule, dilate medullary arterioles
Vasodilator prostaglandins: PGI2 and PGE2. (under normal conditions, don't alter renal blood flow, but with Na+ or volume depletion, they maintain.)
Effect of NO on renal blood flow: Activates soluble guanylyl cyclase to relax vascular smooth muscle cells - Inhibits Na+ reabsorption in distal tubule.
Effects of ANP: 1) Dilates AFFERENT arteriole to increase GFR.
2) Decrease Na+ reabsorption through amiloride-sensitive Na+ channels (thru cGMP).
3) Inhibits secretion of aldosterone, AngII and renin.
4) results in natriuresis and diuresis.
2 areas of great pressure drop in renal vasculature: afferent and efferent arteriole - regulation of BF
Cells that secrete renin: Juxtaglomerular cells
Features of peritubular capillary beds: Fenestrated, low hydrostatic pressure, high oncotic pressure - all facilitate reabsorption.
Control mechanisms of renal blood flow: myogenic tone (stretch stimulates contraction - buffers changes in systemic pressure), tubuloglomerular feedback (macula densa senses decreased NaCl and causes renin release and decreases afferent arteriolar resistance), sympathetic tone, RAS, other hormones
Factors that increase sensitivity of tubuloglomerular feedback: Volume contraction, adenosine, PGE2, Thromboxane, HETE, Angiotensin II
Factors that decrease sensitivity of tubuloglomerular feedback: Volume Expansion, ANP, NO, cAMP, PGI2, high protein diet
Effect of sympathetic nervous system on renal vasculature: 1) VSMC have alpha receptors - constrict, decrease RBF (thru Gq, PLC)
2) juxtaglomerular cells have beta-1 receptors - release renin (thru Gs, AC, cAMP)
Regulators of renin secretion: 1) decreased NaCl at macula densa increases renin.
2) sympathetic stimulation increases renin.
3) Decreased stretch or shear increases renin.
4) increased intracellular Ca2+ INHIBITS renin release.
Effects of Angiotensin II (5): Constricts afferent and efferent arterioles, promotes Na+ and water resorption, constricts systemic vasculature, increases NE release, stimulates thirst and ADH in hypothalamus, stimulates aldosterone release.
Effects of aldosterone (2): increases Na+/K+ ATPase activity in basolateral membrane of distal tubule, increases luminal Na+ and K+ permeability. (Na+ and water resorption)
Effects of ADH (2): stimulates water resorption in collecting duct, increases urea reabsorption in collecting duct.
Effect of ET-1 on ET-A receptors: constrict cortical arteries and mesangial cells (increase blood pressure)
Effect of ET-1 on ET-B receptors: Inhibit Na+ reabsorption in the distal tubule and cause vasodilation of medullary arterioles (decrease blood pressure).
Why should Cox inhibitors be avoided during dehydration or stresses like surgery?: Under these conditions, PGE2 and PGI2 cause vasodilation and prevent too much vasoconstriction of afferent arteriole - maintain renal blood floow. If blocked, could cause acute renal failure.
Renal effects of blocking NO production: sodium retention, hypertension, block sensitivity of TGF
What is the filtration fraction?: The amount of plasma that is filtered in the glomerulus - about 20%
3 layers of filtration barrier: 1) fenestrated endothelium
2) Basement membrane
3) Epithelium (podocytes with filtration slits)
All these surfaces have highly negatively charged glycoproteins
Layers of glomerular basement membrane: lamina rara interna, lamina densa, lamina rara externa
Cutoff size for things passing through glomerulus: 70,000 kDa - but charge matters:
Albumin is 65,000, but has over 200 neg. charges, so will not be filtered
Amount of filtrate reabsorbed: 99% under normal conditions
Regulation of GFR: hydrostatic pressure in glomerulus and Bowman's capsule, oncotic pressure in glomerular capillary, Oncotic pressure in Bowman's space (O)
Starling equation: GFR = Kf * [(Pgc - Pbs) - pgc]
Features of Kf (filtration coefficient): Index of health of filtration barrier, Normally 12.5 mL/min*mmHg, change in Kf chronically alters GFR, hormones and disease can alter Kf (DM), Kf acutely modified by contraction of mesangial cells
Normal values of Starling forces: 1) Pgc = 45 mmHg
2) Pbs = 10 mmHg
3) pgc = 19 mmHg
4) Net filtration = 45 - 10 - 19 = 16 mmHg
Effect of constriction of afferent arteriole: Decrease in RPF and GFR
Effect of dilation of afferent arteriole: Increases Pgc and GFR
Effect of constriction of efferent arteriole: Decreases RPF and Increases GFR, Pgc
Effect of dilation of efferent arteriole: Decreases Pgc and GFR
Effect of constriction of both efferent and afferent arterioles: Dereased flow - increases oncotic pressure - decreases GFR
Effect of increased protein concentration on GFR: decreases GFR
Effect of decreased protein concentration on GFR: increases GFR
Equation relating GFR and clearance of marker: GFR = uv/p
u = urine [marker] (mg/dL)
v = urinary flow rate (mL/min)
p = plasma [marker] (mg/dL)
Reference values for urinary creatinine clearance: males: 94 - 110 mL/min
females: 72 - 110 mL/min
Normal BUN/creatinine ratio: 12-20:1
Factors affecting GFR: Renal Dz, DM, HTN, urinary tract obstruction, decreased RBF or increased plasma protein, decreased angiotensin II, increased sympathetic activity or vasoconstrictor autocoids, pregnancy
equation for amount of substance reabsorbed: [X] reabsorbed = GFR * [Px] -([Ux] * V)
5 important substances that are >99% reabsorbed by kideny: Water, sodium, bicarb, chloride, glucose
Part of nephron where glucose is actively reabsorbed: Glucose is actively cotransported with Na+ by a saturable mechanism in the PCT
Filtered Load: GFR * plasma [X]
Transport max for glucose: 375 - 400 mg/min
(plasma threshold ~180 - 220 mg/dL)
Substances that competitively inhibit glucose reabsorption: sulfates, amino acids, uric acid, organic acids
Part of nephron where urea is passively reabsorbed: PCT - no transport maximum for urea. Slower flow = more urea reabsorption.
Part of nephron where urea reabsorption is dependent on ADH: DCT - ADH increases premeability of DCT and water comes in, bringing urea with it
Substance used to estimate RPF: PAH (para-aminohippuric acid)
PAH is actively secreted by PT cells.
Substances reabsorbed in the early proximal convoluted tubule: Na+, Glucose, amino acids, HCO3-, water
Substances reabsorbed in late proximal convoluted tubule: K+, Cl-, HCO3-, Ca2+, Mg2+, water
Substance secreted in proximal convoluted tubule: H+, organic acids
substances absorbed in thin descending loop of Henle: Water, salt, urea
Channel in Thick ascending loop of Henle responsible for countercurrent gradient: Na+/2Cl-/K+
Substances actively secreted in thick ascending loop of Henle: H+, K+
Channel in Early distal tubule: Thiazide sensitive Na+ and Cl- channel
Two cell types in the late distal convoluted tubule: Principal cell (hormone responsive - Na+, Cl- reabsorption, K+, Cl- secretion, H20 fm ADH), intercalated cell (acid-base balance)
Mechanism of Aldosterone increase of Na+ resorption in distal tubule, CCD, MCD: Increases transcription of Na+ channels, Na+/K+ ATPases in principal cells
Function of intercalated cells of the late distal tubule and collecting duct: Acid-base balance by K+/H+ ATPase, H+ pump, increase HCO3- with acidosis, No aquaporin
Site of regulation of aldosterone: Early distal tubule/collecting duct (increases reabsorption of NaCl, water, increase secretion of K+)
Site of regulation of angiotensin II: Proximal convoluted tubule (increases reabsorption of NaCl, water)
Site of regulation of ADH: Late DT, CCD/MCD (increase reabsorption of water and urea)
Site of regulation of ANP: Distal convoluted tubule/collecting duct (decrease NaCl reabsorption)
Site of regulation of PTH: Proximal convoluted tubule, TALH, Distal tubule (decrease PO4- and increase Ca2+ reabsorption)
Titratable acids (urinary buffers for secreting H+): PO4-, creatinine, sulfates
substance secreted in proximal tubule in times of acidosis: NH4+ (forms NH3 - bicarb is formed, NH4+ is recycled in medulla - diffuses into collecting duct, binds H+ and excreted as H2CO3)
Mechanism of ADH action: ADH binds to V2 receptors on principal cells in collecting duct - stimulates AC - cAMP - pKA - phophorylates proteins in vesicles containing aquaporin - vesicles fuse to PM and create channels for H2O. Also: increases urea permeability, stimulates PGE2
Regulation of ADH secretion: 1) Blood pressure (baroreceptors in aortic arch, carotid sinus, L atrium, pulmonary vessels - input to hypothalamus)
2) Plasma osmolality
Osmoreceptors in hypothalamus sense when rises above a certain set point
Equation for free water clearance: CH2O = V - (Uosm * V/Posm)
Nephrotic Syndrome: >3g/24 hr proteinuria, edema, hypoproteinemia, hyperlipidemia
Nephritic syndrome: hematuria, proteinuria, renal insufficiency, hypertension
Minimal change glomerulopathy findings: Microvillous transformation, foot process fusion, No glomerular lesion. IF: no or slight immune deposition. Good prognosis, steroid responsive, childhood nephrotic syndrome.
Focal segmental glomerulosclerosis findings: Less than 50% of glomeruli have lesion, only part of glomerulus involved. Amorphous electron dense material and cellular debris, lipid laden cells, FSGS with hyalinosis, adhesions. IF: focal segmental IgM and C3, poss slight mesangial IgM and C3. Poor prognosis, not steroid responsive.
Membranous glomerulopathy findings: Most common cause of idiopathic nephrotic syndrome in adults. SUBEPITHELIAL deposits. Diffuse global capillary wall thickening, GBM irregularities. IF: diffuse global capillary wall granular staining for Ig and C.
Membranoproliferative glomerulonephritis findings: Mixed nephrotic/nephritic syndrome with hypocomplementemia.
MPGN type I findings: Type I: immune complex mediated, extensive subendothelial deposits and mesangial interposition. diffuse global hypercellularity with hypersegmentation, thickened cap walls, doubled GBM, varying number of PMN. IF: diffuse global capillary wall pseudolinear to granular Ig and C.
MPGN type II findings: Dense deposit disease. Dense transformation of GBM. Diffuse global hypercellularity with hypersegmentation and thickened cap walls. IF: pseudolinear cap wall and coarse granular mesangial C3.
Diabetic Glomerulosclerosis findings: Light: very thick GBM, mesangial matrix expansion - can produce Kimmelstiel-Wilson nodules. IF: linear staining of BM for IgG (ionic binding secondary to abnormal glycosylation)
Amyloidosis findings: Light: pale acidophilic amorphous material (birefringent with Congo Red) effacing portions of glomeruli, vessels, interstitium. IF: specific staining for amyloid AA or AL protein.
Electron dense immune complex deposits in mesangium: IgA nephropathy
Electron dense subendothelial immune complex deposits: MPGN and class IV lupus GN
GBM thickening: diabetic glomerulosclerosis
GBM thinning: thin BM nephropathy
GBM replication: MPGN
collagenous matrix expansion: sclerosis and/or hyalinosis (FSGN, amyloidosis)
Thin basement membrane nephropathy findings: Familial dz. Benign hematuria. Glomeruli unremarkable by light. Electron micro: reduced thickness of lamina densa. No findings on IF.
IgA nephropathy findings: varied clinical presentation: asymptomatic hematuria to renal failure. Slowly progressive course. Range of histo: no change to focal/diffuse hypercellularity to chronic sclerosing GN. IF: diffuse global granular mesangial IgA and C.
Acute post-infectious GN findings: Immune complex deposition. 1-2 weeks post-strep. Light: diffuse enlargement, hypercellularity, neutrophil infiltration, subepithelial HUMPS. IF: Diffuse global coarse granular capillary wall for IgG and C3, and along the BM.
Lupus GN findings: Widely varied clinical presentation and pathology. Class I: mesangial IC - mild hematuria/proteinuria.
Class II: mesangial IC with hypercellularity - mild hematuria/proteinuria.
Class III: Mesangial and subendothelial IC - Moderate nephritis.
Class IV: Mesangial and Subendothelial IC - Severe Nephritis.
Class V: Subepithelial, mesangial IC - Nephrotic syndrome.
Class VI: variable - chronic renal failure.
Crescentic glomerulonephritis (rapidly progressing GN) findings: Crescents in some or all glomeruli, tuft shows features of inflammation and/or necrosis. Usually caused by immune complex dz in children and ANCA dz in adults.
Anti-glomerular Basement Membrane antibody GN findings: linear glomerular basement membrane staining for IgG, serologic detection of circulating anti-GBM Ab, crescenting glomeruli. Rare, but aggressive. Ab to Type IV collagen.
ANCA GN findings: Glomerular necrosis, crescents, no Ig deposits. 75% have necrotizing systemic small vessel vasculitis.
Three diseases associated with ANCA Ab.: Wegener's granulomatosis (small vessel vasculitis, necrotizing granulomas - usu. respiratory, usu C-ANCA), Churg-Strauss Syndrome (eosinophilia and asthma - usu P-ANCA), Microscopic polyangiitis (small vessel vasculitis - usu P-ANCA).
Proteins targeted by ANCA: myloperoxidase (MPO-ANCA; perinuclear staining = P-ANCA) or proteinase 3 (PR3-ANCA; cytoplasmic staining = C-ANCA) usually in neutrophils and monocytes.
Henoch-Schonlein purpura: Most common childhood vasculitis. IgA immune complex deposition in vasculature. Involves skin, gut, glomeruli. Arthralgias, arthritis.
Cryoglobulinemic GN: Type I MPGN phenotype. Type I - IgM, Type II - rheumatoid IgM complex w/IgG, Type III - polyclonal. Most patients have hepatitis C.
Hypertensive nephrosclerosis: Renal vascular and glomerular sclerosis caused by mild to moderate HTN. Hyaline arteriolosclerosis.
Malignant nephrosclerosis: Renal injury caused by malignant HTN. Thrombotic microangiopathy, fibrinoid necrosis of arterioles, GBM doubling, wrinkling, mesangial congestion.
Acute tubuar Necrosis: rapidly rising serum creatinine usu associated with oliguria. Swollen kidneys with pale cortex and congested medulla. Flattened epithelium in tubule and loop of henle, dilation of lumens, loss of brush border, necrosis.
Causes of acute tubular necrosis: Ischemia (hemorrhage, burns, dehydration, prolonged diarrhea, congestive heart failure), Nephrotoxins (aminoglycosides, amphoB, radiographic contrast, heavy metals, organic solvents, paraquat)
Pathology of drug induced (hypersensitivity) acute tubulointerstitial nephritis: patchy infiltration of cortex, and some medulla by lymphocytes and eosinophils. PCT and DCT have focal invasion. Glomeruli and vessels not invaded.
Drugs causing acute tubulointerstitial nephritis: NSAIDs, diuretics, beta-lactam antibiotics.
Cause of acute pyelonephritis: Gram-negative bacteria from feces (mostly e.coli) cause 80%.
Pathology seen in acute pyelonephritis.: kidneys have small white abscesses on subcapsular surfaces and cut serface. The epithelium of pelvis and calyces is hyperemic with purulent exudate.
Clinical symptoms of acute pyelonephritis: fever, chills, sweats, malaise, flank pain, costovertebral angle tenderness. Leukocytosis with neutrophilia, casts in urine.
Chronic pyelonephritis pathology: atrophy, scarring, contraction of papillary tip, thinning of cortex, deformed calyces, corticomedullary scarring.
Pathology of Light chain (multiple myeloma) cast nephropathy: numerous dense hyaline casts in distal tubules and collecting ducts - eosinophilic and glassy, often with fractures and angular borders.
Pathogenesis of light chain (multiple myeloma) cast nephropathy: circulating monoclonal light chains cross glomerular capillaries and precipitate, causing obstruction.
1) What disease is depicted? 2) Describe the pathology. 3) What would you expect to see on IF?: 1) Acute post-infectious glomerulonephritis.
2) Subepithelial humps = dense deposits of immune complexes. Diffuse granular hypercellularity with numerous PMNs.
3) Diffuse and Global coarse Granular capillary wall IgG and C3.
1) What disease process is depicted? 2) what are clinical findings?: 1) Acute post-infectious GN
2) hypocomplementemia, hematuria, proteinuria, decreased GFR, oliguria, salt and water retention, edema, HTN.
1) What disease is depicted? 2) Describe the pathology. 3) what is the prognosis? 4) What would you expect to see on IF?: 1) Minimal change glomerulopathy.
2) microvillous transformation and foot process fusion.
3) Common cause of childhood nephrotic syndrome: good prognosis, steroid responsive.
4) no or only slight immune deposition.
1) what disease is depicted? 2) what is the pathogenesis?: 1) minimal change glomerulopathy.
2) theory suggests a role for a T-lymphocyte derived factor.
1) What disease is depicted?2) Describe the pathology. 3) What is the prognosis?: 1) FSGS
2) amorphous electron dense cellular debris, lipid laden cells.
3) poor prognosis; non-steroid responsive.
1) What disease is depicted? 2) What are secondary causes? 3) What are clinical findings?: 1) Minimal change glomerulopathy.
2) Hodgkin's dz, NHL, allergy, lithium, NSAIDs, AIDS, diabetes, congenital.
3)significant proteinuria and pitting edema, periorbital edema.
1) What disease is depicted? 2) What are secondary causes? 3) What are clinical findings?: 1) Minimal change glomerulopathy.
2) Hodgkin's dz, NHL, allergy, lithium, NSAIDs, AIDS, diabetes, congenital.
3)significant proteinuria and pitting edema, periorbital edema.
1) What disease is depicted? 2) Describe the pathology. 3) What would you see on IF?: 1) Membranous glomerulopathy.
2) Subepithelial deposits, diffuse global capillary wall thickening with GBM spikes.
3) Diffuse global capillary wall granular staining for Ig and C
1) What disease is depicted? 2) What is the etiology?: 1) primary membranous glomerulopathy.
2) idiopathic - most likely secondary to in situ Ab-Ag immune complex formation.
1) What disease is depicted? 2) What is the etiology? 3) Describe the pathology.: 1) Secondary membranous glomerulopathy.
2) autoimmune dz (lupus), drug exposure (gold), infection (HepB), malignancy, renal vein thrombosis.
3) subepithelia deposits AND mesangial and small subendothelial dense deposits.
1) What disease is depicted? 2) Describe the pathology. 3) What is the etiology? 4) What would you see on IF? 5) What would you see clinically?: 1) MPGN type I
2) Subendothelial deposits, circumferential mesangial interposition, diffuse hypercellularity, thickened capillary walls, doubled GBMs and PMNs.
3) Immune complex mediated - infection (Hep C), cryoglobulinemia.
4) Diffuse global capillary wall pseudolinear to granular Ig and C.
5) mixed nephrosis/nephritis, hematuria, hypocomplementemia.
1) What disease is depicted? 2) What would you see on EM? 3) Describe the IF.: 1) MPGN Type I
2) subendothelial deposits, mesangial interposition.
3)diffuse global capillary wall pseudolinear to granular Ig and C.
1) What disease is depicted? 2) What characteristic lab result is expected? 3) Has a high recurrence with ______: 1) MPGN Type II (dense deposit disease)
2) hypocomplementemia
3) renal transplants
1) What disease is depicted? 2) What is a characteristic light microscopy finding? 3) What would you see on IF?: 1) Diabetic glomerulosclerosis.
2) Kimmelsteil-Wilson nodules
3) linear staining of GBM for IgG
1) What disease is depicted? 2) What is the pathogenesis? 3) This is the most common cause of ______ in the US.: 1) Diabetic Glomerulosclerosis.
2) Increased abnormal glycosylation of IgG.
3) ESRD.
1) What disease is depicted? 2) Describe the IF.: 1) Diabetic glomerulosclerosis.
2) Linear staining of BM for IgG - IgG binds to collagen secondary to abnormal glycosylation.
1) What disease is depicted? 2) What is the characteristic finding shown?: 1) Diabetic glomerulosclerosis.
2) Kimmelsteil-Wilson nodules.
1) What disease is depicted? 2) What would you see on IF? 3) What is it associated with?: 1) Amyloidosis.
2) Specific staining for amyloid AA or AL.
3) plasma cell dyscrasia, neoplastic, or chronic inflammatory conditions.
1) What disease is depicted? 2) What would you see on IF? 3) Describe the pathology.: 1) Amyloidosis.
2) Specific stain for amyloid (AA or AL).
3) fluffy, pale pink "cotton candy" appearance throughout mesangium, can also involve vessels and interstitium.
1) What disease process is depicted? 2) In what syndrome will this be seen, and what are the clinical characteristics.: 1) Hematuria (red blood cell casts in urine - active urine sediment)
2) Nephritic syndrome: hematuria, proteinuria, decreased GFR, increased BUN, creatinine, oliguria, salt and water retention, edema, HTN.
1) What disease is depicted? 2) What is the clinical presentation? 3) What would you see on IF?: 1) Thin Basement Membrane dz. (benign familial hematuria)
2) asymptomatic hematuria - do not develop renal failure, usually don't have proteinuria.
3) Nothing on IF.
1) What disease is depicted? 2) Describe the pathology.: 1) Thin basement membrane glomerulopathy (benign familial hematuria)
2) reduced thickness of lamina densa, normal podocytes, everything else normal.
1) What disease is depicted? 2) What is the etiology? 3) What is the clinical presentation?: 1) Alport's Syndrome.
2) Genetic (mostly X-linked dom, could be AR, AD). Primary defect in Type IV collagen.
3) hematuria - may be assoc with proteinuria, HTN, chronic renal failure, bilateral sensorineural hearing loss, ocular changes in lens, retina, or cornea
1) What disease is depicted? 2) Describe the pathology.: 1) Alport's Syndrome.
2) Foam cells in the interstitium of an inflamed kidney.
1) What disease is depicted? 2) What is the pathogenesis? 3) Describe the pathology.: 1) IgA nephropathy.
2) Antigen has not been determined - IgA immune complex deposition. Patients often have elevated blood levels of IgA.
3) Variable. Focal segmental to diffuse global mesangial cell hyperplasia.
1) Describe the histology. 2) What are the most frequent causes in children and adults? 3) what clinical syndrome is often produced?: 1) Crescentic glomerulonephritis.
2) Children: immune complex diseases. Adults: ANCA.
3) RPGN
1) What disease is depicted? 2) Describe the IF. 3) What is seen on light microscopy and EM?: 1)Acute post-infectious GN.
2)Capillary wall deposition of immune complexes - punctate "christmas tree light" pattern.
3) hypercellular, can't see open capillary loops, neutrophilic infiltration. On EM: large subepithelial humps.
1) What disease is depicted? 2) Describe the characteristic feature.: 1) Acute post-infectious GN.
2) subepithelial humps, may be a few mesangial immune deposits.
1) What disease is depicted? 2) What would you see on IF?: 1) Lupus nephritis.
2) "full-house" staining, IgG usually dominant, C1q present. Everything stains.
1) What is the disease process depicted? 2) What would you see in the urine? 3) What are some causes?: 1) Acute Tubular necrosis.
2) dirty brown granular casts
3) dehydration, CHF, burns, shock, hemorrhage.
1) What is the disease process depicted? 2) Is this reversible? 3) What would you expect to see for each of the following: Serum creatinine, urine output, BUN?: 1) Acute Tubular Necrosis.
2) Yes - this is reversible.
3) Increased serum Creatinine, oliguria, increased BUN.
1) What is the disease process depicted? 2) what are the two types?: 1) Acute tubular necrosis.
2) ischemic and nephrotoxic.
1) What is the disease process depicted? 2) What is the pathogenesis? 3) What drugs are implicated?: 1) Acute tubulointerstitial nephritis.
2) Type IV cell-mediated response to drug - lymphocytic and eosinophilic infiltrate.
3) Ibuprofen, Naproxen, Thiazide diuretics, ACE inhibitors, penicillins, beta-lactams, sulfa drugs.
1) What is the disease process depicted? 2) What cell type is prominent in the infiltrate? 3) What might be seen in the urine?: 1) Acute tubulointerstitial nephritis.
2) eosinophils (also lymphocytes).
3) WBC casts in urine.
1) What is the disease process depicted? 2) Describe the pathology.: 1) acute tubulointerstitial nephritis.
2) Normal glomeruli, interstitium filled with a sea of lymphocytes and eos. Tubules effaced.
1) What is the disease process depicted? 2) Describe the pathology. 3) What is the clinical picture?: 1) Acute pyelonephritis.
2) Tubules containing WBC casts - neutrophils and lymphocytes.
3) Fever, chills, sweats, malaise, flank pain, CVA tenderness, leukocytosis, WBC casts in urine.
1) What is the disease process depicted? 2) What is the pathogenesis? 3) Describe the pathology.: 1) Chronic pyelonephritis.
2) recurrent bacterial infection with urinary tract obstruction, urine reflux, or both.
3) atrophy, scarring, thinning of cortex, calyectasis.
1) What is the disease process depicted? 2) What are two features shown in the histology? 3) What is commonly seen on higher power?: 1) Chronic pyelonephritis.
2) Calyectasis, cortical thinning.
3) Thyroidization - atrophic tubules.
1) What is the disease process depicted? 2) Describe the pathology. 3) What is the pathogenesis?: 1) Chronic pyelonephritis.
2) "Thyroidization" - atrophic tubules.
3) urinary tract obstruction or urine reflux - chronic bacterial infection.
1) What is the disease process depicted? 2) What is the pathogenesis? 3) Describe the pathology.: 1) Light chain (myeloma) cast nephropathy.
2) Monoclonal light chains cross into tubules, mix with urinary proteins, and obstruct tubules.
3) Pink mass of obstructing light chains, with multinucleate giant cell attempting to engulf.
1) What is the disease process depicted? 2) Describe the pathology. 3) In what disease would this be seen?: 1) Light chain nephropathy.
2) fractured casts of light chains/proteins with multinucleate giant cell.
3) Multiple myeloma.
1) Where is renal K+ regulated? 2) What are the channels utilized?: 1) The principal cell of the cortical collecting duct.
2) ROMK - usually open, responds to incoming Na+.
MaxiK - Not as often open, but opens with increased urine flow.
What are some causes of hypokalemia?: Metabolic acidosis, increased beta-adrenergic, vomiting, diarrhea, loop and thiazide diuretics, primary mineralocorticoid excess, secondary hyperaldosteronism due to renal artery stenosis, renal tubular acidosis, insulin.
What are some causes of hyperkalemia?: metabolic acidosis, hyperglycemia, beta-blockade, tissue breakdown, exercise, reduced GFR, volume depletion, hypoaldosteronism, K+ sparing diuretics, adrenal insufficiency.
1) What is the disease process depicted? 2) What protein is involved?: 1) C-ANCA.
2) MPO-ANCA (C-ANCA) this is cytoplasmic staining of neutrophils.
1) What is the disease process depicted? 2) What is the protein involved?: 1) P-ANCA
2) MPO-ANCA (P-ANCA) This is perinuclear staining of neutrophils.
1) What is the disease process depicted? 2) What are three systemic diseases associated with this type of dz process?: 1) ANCA stained neutrophils.
2) Microscopic polyangiitis, Wegener's granulomatosis, Churg-Strauss syndrome.
1) What is the site of action of Carbonic anhydrase inhibitor diuretics? 2) Name an example. 3) How do they work? 4) When are they used? 5) Side effects?: 1) PCT
2) Acetazolamide
3) Blocks breakdown of H2CO3 to H+ and HCO3-, decreases Na+ reabsorption thru Na+/H+ exchange, causes K+ loss.
4) open angle glaucoma, mountain sickness.
5) Creates a mild metabolic acidosis - good for mountain sickness - stim resp.
1) Where is the site of action of Osmotic diuretics? 2) Name an example. 3) How do they work? 4) When are they used? 5) Side effects?: 1) PCT and descending limb Loop of Henle.
2) Mannitol.
3) Freely filtered, but not reabsorbed by tubules - inhibits water and solute reabsorption by increasing osmolarity of tubular fluid.
4) Cerebral edema.
5) hypernatremic dehdration if water not replaced.
1) What is the site of action of Loop diuretics? 2) Name an example. 3) How do they work? 4) When are they used? 5) Side effects?: 1) Thick ascending loop of Henle.
2) Furosemide, Bumetanide.
3) Blockage of Na+/K+/2Cl- transporter. Blocks sodium reabsorption and increases K+, Ca2+, Mg2+ and H+ excretion.
4) Edema from congestive heart failure, cirrhosis, nephrotic syndrome, hypercalcemia.
5) hypomagnesemia, metabolic alkalosis.
1) What is the site of action of Thiazide diuretics? 2) Name an example. 3) How do they work? 4) When are they used? 5) Side effects?: 1) Early DCT.
2) hydrochlorothiazide.
3) Blockage of thiazide-sensitive Na+/Cl- transporter.
4) Drug of choice for Tx of hypertension. Tx mild edematous conditions, diabetes insipidus.
5) hyponatremia, hypercalcemia, metabolic alkalosis, hyperglycemia, hyperlipidemia, hyperuricemia (gout).
1) What is the site of action of Potassium Sparing diuretics? 2) Name three examples. 3) How do they work? 4) When are they used? 5) Side effects?: 1) Principal cells of late DCT, Collecting tubules.
2) Spironolactone, amiloride, triamterene.
3) Spironolactone blocks mineralocorticoid receptors (aldosterone), triamterene and amiloride block Na+/K+ exchange.
4) Combination with more proximal-acting diuretics to prevent K+ loss; Mild edema, Spironolactone can tx hirsutism in women.
5) gynecomastia (spironolactone)
What enzymes are important in thyroid hormone synthesis?: peroxidase - adds I and couples DIT.
What is the mechanism of thyroid hormone action?: T4/T3 binds diffuses across PM, binds nuclear receptor, localized to nucleus and associates with another T3 or RXR, binds to TRE and alters transcription rates.
How is thyroid hormone release regulated?: Hypothalamus releases TRH - causes pituitary to release TSH - causes thyroid to release T4. T3 feeds back and inhibits release of TSH and TRH.
What lab findings would be expected in a patient with hyperthyroidism caused by a pituitary adenoma?: Very high TSH, high T4.
What lab findings would be expected in a patient with hyperthyroidism caused by overingestion of thyroxine?: Low TSH, High T3/T4, low thyroglobulin level.
What are Thianomides, and what are they used for?: propothiouracil (PTU) and Methimazole. These block synthesis of thyroid hormone. Useful in Graves, adenomatous dz, TSH secreting tumor.
What are lab findings in thyroid hormone resistance: generalized, at pituitary and at periphery?: Generalized: no clinical findings, increased TSH, T4.
Pituitary: hyperthyroid Sx, increased TSH, T4.
Periphery: hypothyroid Sx, TSH and T4 normal.
What is meant by euthyroid sick?: With acute and chronic illness, TSH is normal, but T4 and T3 are low. NO need to tx. Resolves with illness.
Symptoms of Craniopharyngioma?: Headache, visual field defects, pituitary deficiency, GH deficiency, diabetes insipidus.
What are the symptoms of a prolactin-secreting pituitary tumor?: amenorrhea, galactorrhea, erectile dysfunction. Can tx w/DA agonist.
What are symptoms of a non-secreting pituitary tumor?: visual field defects, headache, pituitary and GH deficiency. Tx w/surgery.
What are symptoms of a GH secreting pituitary tumor?: gigantism (child), acromegaly (adult), high IGF1. Tx w/surgery, somatostatin.
What are symptoms of an ACTH secreting pituitary tumor?: hypertension, hypokalemia, hypercortisolemia, Cushing's sx. Increased cortisol, ACTH. Tx w/surgery.
1) What disease is depicted? 2) What is the etiology?: 1) Hashimoto's thyroiditis.
2) autoimmune thyroid destruction.
1) What is the disease process depicted? 2) What is the etiology?: 1) Graves' Disease.
2) Autoimmune disorder - thyroid stimulating immunoglobulin.

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Number of cards 242