Lecture 5+6+DLA

Question 1

edematous states

Answer 1

increased NaCl reabsorption → water retention & blood
volume

ex: 
HF
hepatic ascites
nephrotic syndrome 
premenstrual edema

Question 2

non-edematous states

Answer 2

hypertension
hypercalcemia
diabetes insipidus

Question 3

diuretics

Answer 3

Inhibitors of renal ion transporters that decrease the
reabsorption of Na+ at different sites in the nephron
(natriuretics)

used:
managing abnormal fluid retention
hypertension

Question 4

site of action of CA inhibitors

Answer 4

proximal tubule (reabsorption of water, K, and Na/ secretion of organic acid and base secreting systems

Question 5

site of action of thiazides

Answer 5

distal convoluted tubule (reabsorption of Cl and Na)

Question 6

site of action of the K sparing and ADH antagonists?

Answer 6

collecting duct (reabsorption of Na and water / secretion of H and K)

Question 7

site of action of loop diuretics

Answer 7

thick ascending loop of henle (reabsorption of Na, K, and Cl also Ca and Mg)

Question 8

loop diuretics

Answer 8

furosemide

Highest efficacy in removing Na+ & Cl from body
Act on ascending limb of Loop of Henle

applications:
managing edema associated with HF, hepatic, and renal disease
moderate to severe hypertension

Question 9

MOA of loop diuretics

Answer 9

act on the ascending limb of loop of henle

Block NKCC2 Na+ /Cl- /K+ cotransporter

more Na, K, and Cl in tubular fluid = more water excretion

Question 10

actions of loop diuretics

Answer 10

• Increased urine output
• Increased K+ excretion
• Increased Ca2+ excretion
• Increased Mg2+ excretion
• Increased prostaglandin synthesis
• Decreased renal vascular resistance
• Increased renal blood flow

Question 11

adverse effects of loop diuretics

Answer 11

• Ototoxicity
• Hyperuricemia
• Acute hypovolemia
• Hypokalemia
• Hypomagnesemia
• Allergic reactions

Question 12

clinical applications of thiazides?

Answer 12

hypertension
HF (mild-mod)
hypercalciuria (useful for kidney stones)

diabetes insipidus
premenstrual edema

Question 13

examples of thiazides

Answer 13

Hydrochlorothiazide

Chlorthalidone (longest duration)

Metolazone (most potent)

Question 14

MOA of thiazides

Answer 14

act at the distal convoluted tubule
block the NCCT Na/Cl transporter

more Na and Cl in tubular fluid
more water excretion

Question 15

actions of the thiazides

Answer 15

• Increased Na+ & Cl- excretion
• Increased K+ excretion
• Increased Mg2+ excretion
• Decreased urinary Ca2+ excretion
• Decreased peripheral vascular resistance

Question 16

adverse of thiazides

Answer 16

Hypokalemia • Hyponatremia • Hyperuricemia • Hyperglycemia • Hyperlipidemia • Hypersensitivity • Sexual dysfunction

Question 17

K sparing examples (aldosterone)

Answer 17

Aldosterone antagonists:

Spironolactone and Eplerenone

Question 18

when to use K sparing? (aldo antagonist)

Answer 18

act at the collecting tubule
used when their is excess aldosterone

must monitor K closely

Question 19

clinical uses of K sparing ( aldo antagonist)

Answer 19

heart failure ( spironolactone)
hypertension
primary hyperaldosteronism
edema

Question 20

K sparing MOA (aldo antagonist)

Answer 20

act act the collecting tubule

Antagonize aldosterone at intracellular cytoplasmic
receptor sites (no transcription) 

less Na reabsorption and decreased K excretion

Question 21

adverse effects of K sparing

Answer 21

aldosterone antagonists

Gastric upset & peptic ulcers

Endocrine effects (antiandrogen)

Hyperkalemia

Nausea, lethargy, mental confusion (rare)

Question 22

K sparing Na channel inhibitors

Answer 22

Amiloride and Triamterene

block the Na channels (less Na/K exchange)

Question 23

MOA of k sparing (Na channel inhibitors)

Answer 23

act on collecting tubule

Directly block epithelial sodium channel (ENaC) →
decreasing Na+ /K+ exchange

decreased Na+ reabsorption & K+ excretion

Question 24

AE of the K sparing (Na channel inhibitors)

Answer 24

Hyperkalemia
Hyponatremia
Leg cramps
GI upset
Dizziness, pruritus, headache & minor visual changes

Question 25

CA inhibitors

Answer 25

Acetazolamide act at the proximal tubular epithelial cells less effective

Question 26

clinical app of CA inhibitors

Answer 26

Glaucoma Epilepsy (used alone or with other antiepileptics) Mountain sickness prophylaxis Metabolic alkalosis

Question 27

MOA of CA inhibitors

Answer 27

Inhibits intracellular carbonic anhydrase Decreases ability to exchange Na+ for H+ Decreases activity of Na+ /K+ ATPase (diuresis) HCO3 - is retained in lumen (increasing urinary pH)

Question 28

AE of the CA inhibitors

Answer 28

``` • Metabolic acidosis • Hyponatremia • Hypokalemia • Crystalluria • Malaise, fatigue, depression, headache, GI upset, drowsiness, paresthesia ```

Question 29

Giant cell Arteritis | where? epi? patho? clinical?

Answer 29

Large Vessel Vasculitis mostly seen in head and neck (temporal A) epi: seen in elderly; more common in women patho: T cell mediated response to an uncharacterised antigen in the vessel wall Pro inflammatory cytokines like TNF (targets for treatment) (+/- Anti endothelial cell antibodies) clinical features: headache facial and jaw pain ocular symptoms

Question 30

micro of giant cell arteritis

Answer 30

Focal, nodular thickening with reduction of lumen due to intimal hyperplasia Granulomatous inflammation of intima and inner media Multinucleated giant cells Fragmentation of internal elastic lamina

Question 31

Takayasu Arteritis

Answer 31

Large Vessel Vasculitis: seen in aortic arch and great vessels, renal, and vertebral A. epi: young women patho: unknown maybe autoimmune features: pulses are weaker or absent in affected vessels ocular and neurological symptoms

Question 32

histology of takayasu arteritis

Answer 32

Destruction and collagenous fibrosis of the arterial media associated with mononuclear infiltrates and inflammatory giant cells

Question 33

Polyarteritis Nodosa

Answer 33

Medium Vessel Vasculitis involved: Medium sized arteries of kidney > heart > liver > gastrointestinal tract (Lungs are spared) epi: seen in young adults patho: Immune complex mediated damage following Hepatitis B (some are unknown) clinical: Kidney: hypertension, hemorrhage, infarction Heart: myocardial infarction, pericarditis, heart failure Liver and GIT: abdominal pain, mesenteric ischemia and infarcts Rashes, gangrene, peripheral neuropathy

Question 34

histo of polyarteritis nodosa

Answer 34

transmural inflammation fibrinoid necrosis patchy involvement

Question 35

Kawasaki Disease

Answer 35

medium vessel coronary arteries are mainly involved epi: cardiac disease in kids patho: Delayed hypersensitivity reaction to newly uncovered vascular antigens (autoantibodies) ``` clinical: Fever Cervical lymphadenopathy Conjunctival and oral erythema "Strawberry Tongue” Blistering Edema of hands and feet /Erythema of palms and soles Desquamative rash Coronary arteritis and aneurysm rupture and hemorrhage MI ```

Question 36

histo of Kawasaki disease

Answer 36

transmural necrotizing inflammation acute inflammatory cells less fibrinoid necrosis can have superimposed aneurysm/thrombosis

Question 37

Buerger Disease

Answer 37

medium vessel tibial and radial arteries are involved epi: young male smokers (less than 40) patho: Smoking tobacco- direct endothelial injury → inflammation and thrombosis clinical: • Raynaud phenomenon and cold sensitivity • Instep foot pain induced by exercise (instep claudication) • Superficial nodular phlebitis (venous inflammation) • Rest pain due to neural involvement

Question 38

histo of buerger disease

Answer 38

thrombus that has microabcesses of neutrophils and INF occlusion of the vessel

Question 39

Granulomatosis with polyangiitis

Answer 39

small vessel triad: necrotizing granulomas of the upper and lower respiratory or both epi: middle aged; more common in men patho: c-ANCA/ PR3-ANCA mediated ``` clinical: • Sinusitis, pneumonitis; Hemoptysis • Mucosal ulcerations • Hematuria • Rashes, myalgia, neuritis ```

Question 40

histo of Granulomatosis with polyangiitis

Answer 40

Ulcerative lesions surrounded by granulomas with geographic necrosis and accompanying vasculitis Necrotizing granulomas are surrounded by a zone of proliferating fibroblasts with giant cells and leukocyte infiltrate Respiratory tract: sinusitis, bilateral nodular infiltrates with cavitations Kidney: crescentic glomerulonephritis

Question 41

Churg Strauss Syndrome

Answer 41

small vessel patho: p-ANCA/ MPOANCA mediated epi: really any age; slightly female more likely clinical: Respiratory tract- attacks of asthma; allergic rhinitis and sinusitis • Skin- palpable purpura • GIT- bleeding • Kidney (uncommon as compared to other small vessel vasculitis)- hematuria and proteinuria • Neuropathy, myocarditis and cardiomyopathy

Question 42

histo of Churg Strauss Syndrome

Answer 42

Pulmonary infiltrates on imaging • Necrotizing granulomatous inflammation- both in vessel wall and extravascular • Tissue eosinophilia as well as peripheral blood eosinophilia • Serology: raised IgE levels

Question 43

Microscopic Polyangiitis (MPA)

Answer 43

small vessel epi: 50-60; more common in males patho: c-ANCA/ PR3-ANCA mediated Antibody responses to antigens such as drugs (e.g., penicillin), microorganisms (e.g., streptococci), heterologous proteins, or tumor proteins ``` clinical: • Hemoptysis, hematuria and proteinuria • Bowel pain or bleeding • Muscle pain or weakness • Palpable cutaneous purpura ```

Question 44

histo of MPA

Answer 44

Segmental fibrinoid necrosis of the media with focal transmural necrotizing lesions No granulomas or eosinophils or nasopharyngeal involvement neutrophils are seen