Lecture 17+18+20

Question 1

all patients with systolic HF take?

Answer 1

ACEi + Beta blocker + diuretic

Question 2

drugs types for diastolic HF

Answer 2

diuretics
ACEi / ARB
ca channel inhibitors
beta blockers

DO not use positive inotropes

Question 3

PDE III inhibitor examples

Answer 3

Inamrinone and Milrinone

Question 4

MOA of PDE inhibitors

Answer 4

Inhibit myocardial cAMP PDE activity → increased cAMP
levels

reduce preload and afterload
increase AV conduction slightly

used for short-term HF treatment

Question 5

dopamine

Answer 5

stimulates dopaminergic and adrenergic

• Lower doses = mainly dopaminergic stimulating
(produce renal and mesenteric vasodilation)
• Higher doses = both dopaminergic & b1 stimulating
(produce cardiac stimulation & renal vasodilation)
• Large doses = stimulate a receptors
(vasoconstriction)

used for: cardiogenic shock

Question 6

Dobutamine

Answer 6

At therapeutic levels the stimulation of b1 -receptors
predominate

potent inotropic effect and mild vasodilation

Used to increase cardiac output in acute management
of heart failure

Question 7

glucagon

Answer 7

Stimulates adenylyl cyclase to produce increased cAMP (by binding to GPCR), leading to potent inotropic and chronotropic effects

produces similar effect as beta agonists

Used as a cardiac stimulant in management of severe
cases of b-blocker over dosage

Question 8

myocardial AP phases

Answer 8

phase 0: rapid upstroke and depolarization
Na channels open (Na into cell)

phase 1: initial repolarization
Na channels close, and K open ( K goes out)

phase 2: Plateau
voltage sensitive Ca channels open
slow inward current (balances with K)

phase 3: repolarization
Ca channels close
K channels open (outward)

phase 4: resting potential
increase depolarization due to increase Na permeability

Question 9

pacemaker AP

Answer 9

phase 0: upstroke
Ca channels open (slow velocity)

phase 3:
Ca channels inactivate; increase in K activation

phase 4:
slow repolarization due to If

Question 10

treatment for abnormal automaticity

Answer 10

decrease the slope of phase 4 depolarization

raise the threshold of discharge

Question 11

treatment for re-entrant circuits

Answer 11

slow conduction

increase the refractory period

Question 12

treatment for afterdepolarizations

Answer 12

slowing conduction

increase the refractory period

Question 13

Class I anti-arrhythmic drugs

Answer 13

class I are fast channel blockers for Na

IA: Quinidine, procainamide, disopyramide
(IB) Lidocaine, mexiletine
(IC) Flecainide, propafenone

Question 14

Class II anti-arrhythmic drugs

Answer 14

Beta blockers (Ca)

Propranolol, metoprolol, esmolol

Question 15

Class III anti-arrhythmic drugs

Answer 15

• inhibitors of repolarization (K+)

Amiodarone, sotalol, dofetilide

Question 16

Class IV anti-arrhythmic drugs

Answer 16

calcium channel blockers (Ca2+)

Verapamil, diltiazem

Question 17

miscellaneous anti-arrhythmic drugs

Answer 17

Digoxin, adenosine, magnesium, atropine

Question 18

Class I MOA

Answer 18

block fast inward Na channels

decrease Na entry; slow raise of phase 0
cause decrease in excitability

Use/state dependence = cells discharging at
abnormally high frequency are preferentially blocked

Question 19

Class IA MOA

Answer 19

slow rate the change in phase 0
prolong phase 3 (inhibit K)

prolonged repolarization

Question 20

Quinidine

Answer 20

Class IA anti-arrhythmic

CA: Suppression of supraventricular and ventricular
arrhythmias

Inhibits CYP 2D6, 3A4 & P-glycoprotein

Question 21

AE of Quinidine

Answer 21

Arrhythmias (torsades de pointes)
SA & AV block or asystole
Nausea, vomiting & diarrhea (30-50%)
Thrombocytopenic purpura
Cinchonism

toxic dose = tachy

Question 22

contraindications of Quinidine

Answer 22

cannot use in those with Heart block

caution in those with heart issues

Question 23

MOA of procainamide

Answer 23

Similar actions to quinidine
• Blockade of Na+ channels in activated state
• Blockade of K+ channels
• Antimuscarinic properties

CA: Suppression of supraventricular and ventricular
arrhythmias

metabolized by CYP2D6
Partly acetylated to N-acetylprocainamide (NAPA) which prolongs duration of action potential

Question 24

AE of procainamide

Answer 24

Reversible lupus-like syndrome (25-30%)

Toxic doses: asystole, induction of ventricular
arrhythmias

CNS effects (depression, hallucination, psychosis)

Weak anticholingeric effects

Hypotension

more prevalent in chronic use

Question 25

contra of procainamide

Answer 25

hypersensitivity, SLE, heart issues (heart block)

Question 26

MOA of Disopyramide

Answer 26

``` Strong negative inotropic effect (> quinidine & procainamide) Strong antimuscarinic properties causes peripheral vasoconstriction Blocks K+ channels ``` CA: Suppression of supraventricular and ventricular arrhythmias

Question 27

AE of disopyramide

Answer 27

Pronounced negative inotropic effects Severe antimuscarinic effects May induce hypotension & cardiac failure without preexisting myocardial dysfunction

Question 28

pathogenesis of nephrotic syndrome

Answer 28

damage to glomerular cells which then increases the permeability of the capillaries to proteins loss of proteins leads to a decreased plasma oncotic pressure... which then leads to the loss of fluid edema and increased lipoproteins

Question 29

risks of having membranous nephropathy

Answer 29

thrombosis: can be venous or arterial patho: 1. Hypercoagulability due to Urinary loss of endogenous anticoagulants (anti thrombin III) Hypoalbuminemia → stimulation of protein synthesis in liver → increased production of coagulation factors Intravascular volume depletion → increased blood viscosity 2. Endothelial dysfunction due to pro inflammatory cytokines

Question 30

symptoms of nephrotic syndrome

Answer 30

heavy proteinuria edema lipiduria hyperlipidemia infection and embolism

Question 31

Minimal Change Disease

Answer 31

benign disorder is characterized by diffuse effacement of foot processes of visceral epithelial cells (podocytes) most common cause of nephrotic syndrome in children (2-6) can sometimes follow a respiratory infection or immunization eitopath: some immune dysfunction that results in the elaboration of factors (“glomerular permeability factors”) that damage visceral epithelial cells and cause proteinuria no immune deposits are seen

Question 32

histo of minimal change disease

Answer 32

electron microscopy = will see effaced/ fused foot processes light = everything looks norm immuno = no depositions

Question 33

clinical features of minimal change disease

Answer 33

* Disease typically manifests with abrupt development of the nephrotic syndrome in an otherwise healthy child * No hypertension * Renal function is preserved in most of these patients * Periorbital edema and generalized edema (anasarca) * Protein loss usually is confined to smaller plasma proteins, chiefly albumin (selective proteinuria) * Prognosis for children with this disorder is favorable – no tendency to develop into a chronic renal failure/end stage kidney disease * More than 90% of children respond to a short course of corticosteroid therapy

Question 34

Focal Segmental Glomerulosclerosis

Answer 34

can be primary (idiopathic) or secondary primary = most common cause of nephrotic syndrome disorder of the podocytes secondary: HIV, obesity, cancer, drug use

Question 35

patho of secondary FSGS

Answer 35

reduction in renal mass due to a renal disease will lead to compensatory hypertrophy and hyperfiltration will have Intraglomerular hypertension Focal and segmental sclerosis in glomeruli

Question 36

micro of FSGS

Answer 36

light: Collapse of capillary loops, increase in matrix, and segmental deposition of plasma proteins along the capillary wall immuno: Negative/ or non-specific granular deposits of IgM and C3 electron: Diffuse effacement of foot processes, and there may also be focal detachment of the epithelial cells and denudation of the underlying GBM

Question 37

Clinical features that differ MCD from FSGS

Answer 37

1. Higher incidence of microscopic hematuria, reduced GFR (renal insufficiency) and hypertension 2. Proteinuria is more often non-selective (more than just albumin) 3. Poor response to corticosteroid therapy 4. Progression to chronic kidney disease (50% develop end stage renal disease within 10 years proteinuria: insidious in onset non-selective more than 3.5

Question 38

Membranous Nephropathy

Answer 38

characterized by diffuse thickening of the glomerular capillary wall due to the accumulation of deposits containing Ig along the subepithelial side of the basement membrane ``` epi: 30-50 more common in males most common cause of nephrotic syndrome in elderly really rare in kids ``` etio: most cases are primary Autoimmune disease caused in most cases by antibodies to a renal autoantigen; most commonly PLA2R (phospholipase A2 receptor) on podocytes secondary: 1. endogenous (SLE, cancer, other Autoimmune conditions) 2. exogenous drugs and infections

Question 39

patho of membranous nephropathy | direct and indirect?

Answer 39

1. antigen-antibody reaction 2. complement activation 3. insertion of MAC into membrane can be direct or indirect damage direct: • Alteration of cytoskeleton • Effacement of foot processes • Detachment of podocyte indirect: • Activation of epithelial and mesangial cells • Proteases, oxidants, cytokines • Stimulation of GBM growth (“spikes”) either way it leads to increased permeability of the BM massive proteinuria

Question 40

histo of membranous nephropathy

Answer 40

light: thickening of the BM silver stain: spike and dome appearance immuno: Granular IgG and C3 deposits around the glomerular basement membrane

Question 41

clinical features of membranous nephropathy

Answer 41

nephrotic syndrome, microscopic hematuria (50%), hypertension some have remission; can develop ESRD or thrombosis

Question 42

Diabetic Nephropathy

Answer 42

Renal disease follows cardiac causes (myocardial infarction) of mortality in patients with diabetes mellitus due to the side effects of hyperglycemia can see: 1. Glomerular lesions 2. Renal vascular lesions, principally arteriolosclerosis 3. Pyelonephritis (tubules and interstitium), including necrotizing papillitis

Question 43

patho of diabetic nephropathy

Answer 43

systemic hyperglycemia leads to increased matrix formation, increased type IV collagen, and hyperfiltration

Question 44

histo of diabetic nephropathy

Answer 44

1. GBM thickening (identified on EM first) 2. Mesangial widening 3. Tubular BM thickening Kimmelstiel-Wilson nodules will be seen can see ischemia hyaline arteriosclerosis

Question 45

NODULAR GLOMERULOSCLEROSIS

Answer 45

Distinctive glomerular lesion characterized by ball-like deposits of a laminated matrix in the periphery of the glomerulus the nodules are PAS + can be seen in those with chronic DM kidneys will be granular and contracted

Question 46

clinical features of diabetic nephropathy

Answer 46

initially the hyperglycemia just leads to hyperfiltration (increased GFR) after a while microalbuminuria occurs after there is persistent & progressive proteinuria, hypertension, highly variable decline in GFR 1-24 ml/min/year

Question 47

renal amyloidosis

Answer 47

kidney will appear to be normal color and shape in extreme cases they might be smaller micro: Amyloid deposited primarily in the glomeruli Interstitial peritubular tissue, arteries, and arterioles are also affected will see deposits along the BM

Question 48

CF of renal amyloidosis

Answer 48

Most common renal presentation: nephrotic syndrome Renal insufficiency is present in 50% at time of Diagnosis. Electrolyte abnormalities (Fanconi syndrome)

Question 49

Nephrotic syndrome

Answer 49

Clinical entity due to glomerular disease characterized by • Heavy proteinuria (>3.5 g/day) • Hypoalbuminemia and severe edema • Hyperlipidemia and lipiduria (lipid in urine)

Question 50

Acute kidney injury

Answer 50

Rapid decline of GFR (within hours to days) Dysregulation of fluid and electrolyte balance Retention of metabolic wastes

Question 51

Chronic kidney disease

Answer 51

Reduced GFR that it persistently less than 60 mL/minute/1.73 sq. m for at least 3 months from any cause and/or persistent albuminuria

Question 52

End stage renal disease

Answer 52

GFR is less than 5% of normal | This is the terminal stage of uremia

Question 53

Renal tubular defects

Answer 53

Polyuria (excessive urine formation) and nocturia Electrolyte disorders Disorders directly affecting tubules or cause defects in specific tubular functions (inherited or acquired)

Question 54

Urinary tract infections

Answer 54

Bacteriuria and pyuria | May infect kidney (pyelonephritis) or bladder (cystitis)

Question 55

Nephrolithiasis (renal stones)

Answer 55

Spasms of severe pain (renal colic) and hematuria

Question 56

Nephritic syndrome

Answer 56

Acute in onset; characterized by Grossly visible hematuria or dysmorphic RBCs and red cell casts in urine Reduced GFR, mild to moderate proteinuria and hypertension