Some CV and renal conditions and DM drugs Flashcards
S3
Early diastole
Associated with INCREASED FILLING PRESSURES (MR, HF); More common in dilated ventricles
Normal in children, pregnant women
S4
Late diastole - ‘Atrial kick’ due to high atrial pressure
Associated with ventricular hypertrophy and stiff LV wall
Best heard in left lateral decubitus
Normal S2 splitting
A2-P2 widens slightly with inspiration
Inspiration -> drop in intrathoracic pressure -> increased venous return -> increased RV filling and SV -> INCREASED RV EJECTION TIME-> Delayed closure of PV in cycle compared to AV
Wide S2 splitting
A2-P2 exaggeratedly split
CONDITIONS THAT DELAY RV EMPTYING (PS, RBBB) -> Delayed PV closure regardless of breath, but increases with inspiration
Fixed S2 splitting
A2-P2 exaggeratedly split and unchanging
OCCURS IN ASD
L->R shunt increases RA/RV volumes -> Delayed PV closure regardless of breath that DOESN’T CHANGE WITH INSPIRATION
Paradoxical S2 splitting
Conditions that delay AV closure (AS, LBBB) -> Reversal of normal valve closure order -> P2-A2 heard
On inspiration -> Increased RV ejection time -> P2 heard later and closer to A2 -> Split narrows instead of widening
Kussmaul sign
Increased JVP on inspiration instead of normal decrease
Due to impaired RV filling with constrictive pericarditis, restrictive cardiomyopathies, tumors in RA/RV
PAN
Medium vessel vasculitis in young adults affecting renal, visceral vascular beds, but NOT PULM aa
Sx based on affected organs
Due to immune complexes -> Fibrinoid necrosis
Associated w/ HBV
micro-PAN
Necrotizing vasculitis commonly involving lung, kidneys, and skin w/ pauci-immune glomerulonephritis and palpable purpura
Presents as granulomatosis with polyangiitis without nasopharyngeal involvement
No granulomas, asthma, or eosinophilia (vs. Churg-Strauss)
Nephritic syndromes
Inflammatory conditions -> Hematuria, RBC casts in urine; Azotemia, oliguria, HTN, mild proteinuria
Acute PSGN, RPGN (crescentic), DPGN, IgA nephropathy (Berger disease), Alport syndrome, MPGN
Nephrotic syndromes
Podocyte damage disrupting glomerular filtration charge barrier -> Massive proteinuria, hypoalbuminemia, hypogammaglobulinemia, edema, hyperlipidemia
Frothy urine with fatty casts
Hypercoagulable state due to ATIII loss
Minimal change disease, FSGS - No IC deposits, podocyte foot process effacement only
Membranous nephropathy, MPGN - Granular IF
Amyloidosis, DM glomerulonephropathy - due to systemic conditions
Acute PSGN
Nephritic
Enlarged, hypercellular glomerulid
Granular IF w/ IgG, IgM, C3 deposition in GBM and mesangium
Subepithelial IC humps, low serum C3
RP (crescentic) GN
Nephritic
Crescent-shaped deposits of fibrin, plasma protein (e.g. C3b), and macrophages
Poor prognosis
Associated w/ Goodpasture syndrome, Wegener’s granulomatosis w/ polyangiitis, and microscopic polyangiitis
DPGN
Mixed nephritic/nephrotic
SLE nephritis - most common COD
Subendothelial or intramembranous IgG ICs w/ C3 deposition - granular IF
IgA nephropathy
Nephritic
AKA Berger disease
IgA IC deposits in mesangium -> mesangial proliferation
Episodic hematuria w/ RBC casts presenting after acute gastroenteritis
Renal pathology of Henoch-Schonlein purpura
Alport syndrome
Nephritic
XR mutation of type IV collagen -> GBM splitting
Retinopathy, lens dislocation, glomerulonephritis, sensorineural deafness
MPGN
Mixed nephritic/nephrotic
T1 - Subendothelial granular ICs w/ ‘tram-track’ appearance due to GBM splitting caused by mesangial ingrowth. Associated w/ HBV, HCV
T2 - Intramembranous dense IC deposits. Associated w/ C3 nephritic factor -> stabilized C3 convertase -> low serum C3
FSGS
Nephrotic
Segmental sclerosis/hyalinosis of glomeruli
Nonspecific IF w/ podocyte foot process effacement
Most common nephrotic syndrome in African Americans, Hispanics. Associated w/ HIV, heroin, sickle cell
Minimal change disease
Nephrotic
Normal glomeruli w/ negative IF, podocyte foot process effacement
Most common in children, often triggered by recent immune stimulus or rarely 2o to lymphoma
Cytokine mediated -> Only nephrotic syndrome w/ good response to corticosteroids
Membranous nephropathy
Nephrotic
Diffuse capillary and GBM thickening
Granular IF w/ ‘spike and dome’ subepithelial IC deposits
SLE nephrosis
Most common in white adults. Associated w/ SLE, HCV, HBV
(MPGN has similar IF deposition and proteinuria)
Amyloidosis
Nephrotic
Mesangial amyloid deposits
Associated w/ chronic immune/inflam conditions - multiple myeloma (cast nephropathy w/ Bence-Jones proteins), TB, RA
Kidney is most commonly involved organ of systemic amyloidosis
DM glomerulonephropathy
Nephrotic
Eosinophilic nodular glomerulosclerosis (Kimmelstiel-Wilson nodules) w/ mesangial expansion, GBM thickening
Due to non-enzymatic glycosylation of GBM (poor charge barrier -> nephrosis) and efferent arterioles (up GFR; give ACE inhibitors/ARBs to DM patients)
Metformin
Down gluconeogenesis, up glycolysis, up insulin sensitivity
Most serious SE is lactic acidosis -> CI in HF, renal insufficiency
Can be used in T1DM - islet fxn not required
Sulfonylurea 1st gen
Chlorpropamide, Tolbutamide
Stimulate release of endogenous insulin in T2DM
Risk of hypoglycemia in renal failure from low drug excretion
1st gen SE: Disulfiram-like rxn
Sulfonylurea 2nd gen
Glimepiride, Glipizide, Glyburide
Stimulate release of endogenous insulin in T2DM
Risk of hypoglycemia in renal failure from low drug excretion
2nd gen SE: Hypoglycemia
Glitazones/TzDs
Pioglitazone, Rosiglitazone
Bind PPAR-g in periphery to up insulin sensitivity in T2DM
SE: Weight gain, edema, HF, osteoporosis
No hepatotoxicity associated w/ current TzDs (but previous versions had this risk)
GLP-1 analogs
Exenatide, Liraglutide
Trigger glucose-dependent insulin release in T2DM
SE: Nausea, vomiting, pancreatitis
DPP-4 inhibitors
Linagliptin, Saxagliptin, Sitagliptin
Block GLP-1 degradation in T2DM
SE: Mild urinary/resp infections
Amylin analogs
Pramlintide
Delays gastric emptying, suppresses glucagon in BOTH types of DM
SE: Hypoglycemia, nausea, diarrhea
SGLT-2 inhibitors
Canagliflozin
Block reabsorption of glucose in PCT in T2DM
SE: Glucosuria causing UTIs, yeast infections
a-glucosidase inhibitors
Acarbose, Miglitol
Block intestinal brush-border a-glucosides to limit glucose absorption -> decreased postprandial hypoglycemia in T2DM
SE: Nausea, vomiting, flatulence
