Pleno Skenario D Blok 7 2012

7/28/2019 Pleno Skenario D Blok 7 2012

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Pleno scenario D

bloc 7

dr.Swanny,MSc

Physiology dept.


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Scenario D

An old lady, 63 years old.

-Hypertensive

-Low salt diet-Diuretic (HCT)

Chief complaint : Lethargy


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Kriteria Hypertensi

menurut JNC7

Kriteria Sistolik (mmHg) Diastolik (mmHg)

Normal < 120 < 80

Prehypertension 120 - 139 80 - 89

Stage I hypertension 140 - 159 90 - 99

Stage II hypertension > 160 > 100


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Total Body Water Distribution


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K+

Mg++

Ca++A-

Na+

Cl-

HCO3-


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Exchange of Water Between Cellular and

Extracellular Fluids

Osmotic Forces

- prime determinants of water distribution in the body

- holds water within a space

Osmosis

- movement of water from one compartment to another

- ECF and ICF are in equilibrium when cell membranes

are freely permeable to water


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Exchange of Water Between Cellular and

Extracellular Fluids

Osmotic gradient

- if one osmotic force is higher in onecompartment osmotic gradient

- water flows from space of low osmolality(less solutes) to higher osmolality (more

solutes)


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Major Osmotic Forces

1. Extracellular osmole

- Na+ salts

2. Intracellular osmole

- K+ salts

3. Vascular Osmoles

- plasma proteins


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Why is Na important?

Osmotic Equilibrium

Osmolality: 280-295 mOsm/Kg H20 85-95% Na is extracellular

Cell function relies on maintenance of body fluid tonicity

Present as disorders of water balance:

Altered Na and Water content: Regulation of volume and osmolality

Alterations in Na levels manifest as:

ECF volume depletion

Hypotension

Tachycardia

ECF volume overload

Peripheral edema

Pulmonary Edema

Water balance regulated through ADH (AVP; vasopressin)

Hypothalamus: Thirst Control Center

Washington Manual of Therapeutics

Palmer, Biff F., John R. Gates, and Malcolm Lader. "Causes and Management of Hyponatremia." The Annals of

Pharmacotherapy37 (2003): 1694-701.


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The Basics:

Plasma Na concentration too LOW


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Water Homeostasis

Sodium = Extracellular Tonicity/Osmolality = Water

balance

Brain Osmoreceptors

Vasopressin

AquaporinChannels in CT Urinary concentration


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Na Regulation

Thirst

ADH most common cause of hypoNa

Excrete dilute urine Retention of H2O (salt to lesser extent)

May be appropriate or inappropriate

RAAS


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ADH

No ADH: ADH Present:


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CNS Manifestations

Osmotic Cerebral Edema

H2O from Plasma Brain cells

Mild: N/V, HA, Malaise

Severe: AMS, Hyporeflexia, Seizures, Coma

Nausea: stimulus for ADH release

Inc ADH H2O retentionWorse HypoNa


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Major Causes

Appropriate ADH Release:

ECV depletion: dec perfusion

True volume depletion

Heart failure (dec CO)

Cirrhosis (Arterial vasodil)

Thiazide diuretics

Physiologic ADH Release:

Pain

Nausea

Inappropriate ADH Release:

Reset osmostat

SIADH

Adrenal Insufficiency

Hypothyroidism

Pregnancy

Appropriate ADH Suppression:

Advanced renal failure Primary polydipsia

Beer Potomania


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Pathophysiology of Hyponatremic State

How do patients develop hyponatremia?

Why do they stay hyponatremic?


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Effective Circulating

Volume Depletion

ADH secretion

Proximal

reabsorption

Thirst K+ loss

Water

intakePlasma

K+

Water retention

Persistent volume depletion

Urine Na+


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Pathophysiologic Factors that Diminish Renal

Water Excretion

Diminished generation of free water in the Loop of

Henle and distal tubule

Decreased fluid delivery into these segments

Effective volume depletion

Renal Failure

Inhibition of NaCl reabsorption

Diuretic use


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Hyponatremia

Types

Hypovolemic hyponatremia

Euvolemic hyponatremia

Hypervolemic hyponatremia

Redistributive hyponatremia

Pseudohyponatremia


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develops as sodium and free

water are lost and/or replaced

by inappropriately hypotonic

fluids

Sodium can be lost through

renal or non-renal routes

www.grouptrails.com/.../0-Beat-Dehydration.jpg


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Nonrenal loss

GI losses

Vomiting, Diarrhea, fistulas, pancreatitis

Excessive sweating

Third spacing of fluids

ascites, peritonitis, pancreatitis, and burns

Cerebral salt-wasting syndrome traumatic brain injury, aneurysmal subarachnoid

hemorrhage, and intracranial surgery

Must distinguish from SIADH

www.jupiterimages.com


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Renal Loss

Acute or chronic renal insufficiency

Diuretics

www.ct-angiogram.com/images/renalCTangiogram2.jpg


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Normal sodium stores and a total body excess

of free water

Psychogenic polydipsia, often in psychiatric

patients

Administration of hypotonic intravenous or

irrigation fluids in the immediate postoperative

period


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administration of hypotonic maintenance

intravenous fluids

Infants who may have been given inappropriate

amounts of free water bowel preparation before colonoscopy or

colorectal surgery


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SIADH

downward resetting of the osmostat

Pulmonary Disease

Small cell, pneumonia, TB, sarcoidosis

Cerebral Diseases

CVA, Temporal arteritis, meningitis, encephalitis

Medications SSRI, Antipsychotics, Opiates, Depakote, Tegratol


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Hypervolemic hyponatremia

Total body sodium increases, and TBW

increases to a greater extent.

Can be renal or non-renal

acute or chronic renal failure

dysfunctional kidneys are unable to excrete the

ingested sodium load

cirrhosis, congestive heart failure, or nephroticsyndrome


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Redistributive hyponatremia

Water shifts from the intracellular to theextracellular compartment, with a resultant

dilution of sodium. The TBW and total body

sodium are unchanged.

This condition occurs with hyperglycemia

Administration of mannitol
http://images.google.com/imgres?imgurl=http://www1.istockphoto.com/file_thumbview_approve/2803967/2/istockphoto_2803967_high_blood_sugar.jpg&imgrefurl=http://www.istockphoto.com/file_closeup/%3Fid%3D2803967%26refnum%3D638407&h=253&w=380&sz=26&hl=en&start=3&tbnid=1x19YVIiAoj7xM:&tbnh=82&tbnw=123&prev=/images%3Fq%3Dblood%2Bsugar%26gbv%3D2%26hl%3Denhttp://www.neurobiology.com/index.html


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Hyponatremia

Pseudohyponatremia

The aqueous phase is diluted by excessive

proteins or lipids. The TBW and total body sodium

are unchanged.

hypertriglyceridemia

multiple myeloma
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Diuretics

Excretion of Water and Electrolytes


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Background

Primary effect of diuretics is to increase solute excretion, mainly asNaCl

Causes increase in urine volume due to increased osmotic pressurein lumen of renal tubule.

Causes concomitant decrease in extra-cellular volume (blood

volume) Certain disease states may cause blood volume to increase outside

of narrowly defined limits

Hypertension

Congestive heart failure

Liver cirrhosis Nephrotic syndrome

Renal failure

Dietary Na restriction often not enough to maintain ECF andprevent edema diuretics needed


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Review of Kidney Structure


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Types of diuretics and therapeutic uses

Loop diuretics (ascending limb of loop)

Hypertension, in patients with impaired renalfunction

Congestive heart failure (moderate to severe) Acute pulmonary edema

Chronic or acute renal failure

Nephrotic syndrome

Hyperkalemia

Chemical intoxication (to increase urine flow)


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Types of diuretics and therapeutic uses

Thiazide diuretics (distal convoluted tubule)

Hypertension

Congestive heart failure (mild)

Renal calculi

Nephrogenic diabetes insipidus

Chronic renal failure (as an adjunct to loop

diuretic) Osteoporosis


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Types of diuretics and

therapeutic uses

Potassium-sparing diuretics (collecting tubule)

Chronic liver failure

Congestive heart failure, when hypokalemia is a problem

Osmotic agents (proximal tubule, descending loop ofHenle, collecting duct)

Reduce pre-surgical or post-trauma intracranial pressure

Prompt removal of renal toxins

One of the few diuretics that do not remove large amounts ofNa+

Can cause hypernatremia


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Nephron sites of action of diuretics


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Background to Mechanisms of Action of Diuretics

Previously told that reabsorption, secretion occurred along renaltubule but not howthis was accomplished

Movement from tubular fluid through renal epithelial cells and intoperitubular capillaries accomplished by three transport mechanismsafter cell interior is polarized by Na+/K+ pump

1. Channels formed by membrane proteins

Allows only sodium to pass through

2. Cotransport Carrier mediated

Simultaneously transports both Na+ and other solute (Cl-, glucose, etc)

from tubular lumen into renal epithelial cell3. Countertransport

Carrier mediated

Transports Na in, another solute (H+) out of renal epithelial cell

Water moves transcellularly in permeable segments or via tight

junctions between renal epithelial cells


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Electrolyte Transport Mechanisms

Channel

Cotransport

Countertransport

Na+/K+ pump

X = glucose, amino

acids, phosphate,etc.


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Mechanisms of Action:

Carbonic anydrase inhibitors

CAIs work on cotransport of Na+, HCO3- and Cl- that is coupled to H+

countertransport

Acts to block carbonic anhydrase (CA),

1. CA converts HCO3-

+ H+

to H2O + CO2 in tubular lumen2. CO2 diffuses into cell (water follows Na

+), CA converts CO2 + H2O intoHCO3

- + H+

3. H+ now available again for countertransport with Na+, etc)

4. Na+ and HCO3- now transported into peritubular capillary

CA can catalyze reaction in either direction depending on relativeconcentration of substrates


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Mechanisms of Action: Loop diuretics No transport systems in descending loop of Henle

Ascending loop contains Na+

- K+

- 2Cl-

cotransporter from lumen to ascending limbcells

Loop diuretic blocks cotransporter Na+, K+, and Cl- remain in lumen, excretedalong with water


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Mechanisms of Action: Thiazide Diuretics in

the Distal Convoluted Tubule

Less reabsorption of water and electrolytes in the distalconvoluted tubule than proximal tubule or loop

A Na+ - Cl- cotransporter there is blocked by thiazides


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Mechanisms of Action: Collecting tubule and

potassium-sparing diuretics

Two cell types in collecting tubule

1. Principal cells transport Na, K, water

2. Intercalated cells secretion of H+ and HCO3

3. Blocking Na+ movement in also prevents K+ movement out


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Types and Names of Diuretics

Osmotic agents Mannitol Proximal tubuleDescending loop

Collecting duct

Carbonicanydrase inhib. AcetazolamideProximal tubule

Thiazides Hydrochlorothiaz

ide

Distal convoluted

tubule

Loop diuretic Ethacrynic acid

Furosemide

Loop of Henle

Type Example Sites of Action

K+

- sparingSpironolactone

Amiloride

Collecting tubule


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Thiazide diuretics

Developed to preferentially increase Cl-

excretion over HCO3- excretion (as from CAIs)

Magnitude of effect is lower because work on

distal convoluted tubule (only recieves 15% of

filtrate)

Cause decreased Ca excretion

hypercalcemia reduce osteoporosis


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Comparison of loop and thiazide diuretics


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Summary

Hypertensive salt restriction

hyponatremia

Hypertensive HCT/ diuretic diuresis and

hyponatremia continues dehydration

hypovolemic hyponatremia


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Thank you

Pleno Skenario D Blok 7 2012

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