9 Coursebook-1 - Pass Program

What is the best next
step?
Case:
19 y/o unmarried, at term pregnant woman
has a MVA 30 minutes ago. She is able to
answer the anamnesis and is lucid. At the
moment she is crying, and seeks for
companion, she is very worried about the
baby because she doesnt feel movements
anymore and ask for the mother to be called.
Temperature is 37C, Pulse 102m, BP 60 over
40. Fetal signs negative. What is the best next
step?
C IRCULATION:
What to check?
-History of profuse bleeding
-Hypotension
-Pale, cool, clammy skin
-Delayed capillary refill
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C IRCULATION:
What to check?
-History of profuse bleeding
-Hypotension
-Pale, cool, clammy skin
- Dry mucosas (Tounge, no tears)
- Depresed fontanelles (children)
-Delayed capillary refill
C IRCULATION:
Then: Restore volume ASAP
1.Two IV lines (16-Gauge)
2. Plenty liquids:
Ringer lactate
Normal saline
Blood
3. If not enough, third line in
saphenous vein
4. Children <4y/o Intraosseus in tibia
or frontal
C IRCULATION:
Then: Control of hemorrhage
- Direct pressure
- Clamping artery
- Curettage if obstetric
C IRCULATION:
Possible causes:
- Trauma in abdomen or thorax (not in
cranium, not enough space to cause

shock)
- Bleeding (obstetric, big wounds)
- Dehydration (deprivation)
- Hyper urination (DI, diuretic overuse)
SHOCK
DUE TO SKIN CO SVO2 SVR PCWP
SEPTIC BACT.
TOXIN
WARM HIGH HIGH LOW LOW
VOLUME BLEEDING
LIQ. DEP
PALE
COLD
LOW LOW HIGH LOW
CARDIO HYPO
MOTILITY
PALE
COLD
LOW LOW HIGH HIGH
NEURO VAGAL
REFLEX
WARM LOW LOW LOW LOW
CO: Cardiac Output
SVR: Sistemic Vascular Resistance
SVO2: Systemic Venous Oxigen
PCWP: Pulmonary Capilary Wedge Pressure
GENERAL:
1) All Trauma Patients: CS, Chest, Pelvic XR
2) If unstable, proceed to laparotomy
3) If abdomen cannot be examined: CT scan
of abdomen and pelvis w/ oral and IV
Contrast
4) Gunshot in abdomen: Laparotomy
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BEST WAY ORGANIZATION:
From HEAD TO TOES
EPIDURAL HEMATOMA:
- Bleeding between skull bone and
dura mater
- Rupture of Middle Meningeal Artery
- PROGRESSION:
- Unconciusness
- Lucid interval
- Coma
EPIDURAL HEMATOMA:
- Anisocoria
- Bi-concave hematoma
- Tx:
1. After trauma, only image
w/o symptoms at all: OBSERVATION
2. Symptoms & Immage:
EMERGENCY SURGERY
EPIDURAL HEMATOMA:
SUBDURAL HEMATOMA:
-Bleeding between dura mater and

arachnoides
- Rupture of veins crossing subdural
space Bridging veins
- Image: Concave hematoma
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SUBDURAL HEMATOMA:
- SEEN TYPICALLY IN:
Elderly, demented, alcoholics
- Tx: 1.If small and no symptoms:
OBSERVATION
2. Affect mental status:
SURGERY
SUBDURAL HEMATOMA:
SUBARACHNOID HEMORRHAGE:
- Bleeding between arachnoides and
pia mater.
- MCC: TRAUMA followed by Ruptured
Berry Aneurism (HTN)
- Blood is seen in ventricles and
around brain (NOT IN BRAIN)
- MOST SEVERE EVER headache.
- Leaves sequelae like epilepsy,
blindness
- IF VIGNETTE LOOKS FOR Dg:
NEVER USE CONTRAST
Tx: If due to anaeurism or AV
malformation, SURGERY
Otherwise: Support, observation or
anti-convulsivats if needed.
-No mases
-No ventricules
-Deviation
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INTRACEREBRAL HEMORRHAGE
-Bleeding into brain parenchima
typically in basal ganglia.
-Due to Trauma, HTN, tumor.
- IF VIGNETTE LOOKS FOR Dg:
NEVER USE CONTRAST
- Tx: Surgery is reserved for large
bleedings if they are accesible.
WHEN DO WE DECIDE FOR
SURGERY IN ANY CASE?
WHEN CT scan OR MRI SHOW
DEVIATION OF MIDDLE
LINE
DIRECT HEAD TRAUMA:
CONSECUENCE:
1
2
3
CONSECUENCE:
- Open or close head injury
- Increased Intracranial Pressure
- Reversible or Irreversible neuronal
damage
- DEAD
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What to do next?
- After ABCs finish PE w/ Glasgow

scale
- Look for signs of Intracranial
Hypertension:
- Decrease in the comma scale
- Anisocoria
- Signs of decerebration
What to do next?
- Elevate head
- Intubate and hyperoxigenate
- Lower CO2
- Mannitol
- Sedation
After stabilization:
- CT scan
- XR of skull (look for fractures)
- If Open Wound (clean and close)
DIFUSE AXONAL INJURY
- High speed injury with stretching or
shearing of brain tissue
- Immage shows petechial hemorrhages in
white matter tracts
- Associated with immediate deep coma,
cerebral edema and elevation of ICP
- High mortality
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DIVIDED IN TWO:
- BLUNT TRAUMA
- PENETRATING TRAUMA
WHAT TO DO IN BLUNT TRAUMA:
- If UNSTABLE: -EXPLORE
Respiratory compromise
Hematoma
Shock
WHAT TO DO IN BLUNT TRAUMA:
- If STABLE: -Look for other symptoms
If patient OK then
REASURANCE
WHAT TO DO IN PENETRATING TRAUMA
- Decide which ZONE is compromised
III
II
I
Necks base to mandibles angle
Mandibles angle to Cricoid
Cricoid to Clavicle
IF ZONE I & III
UNSTABLE:
1) A, B, C always first!
2) Surgical exploration
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IF ZONE I & III
STABLE:
1) Endoscopy of: Respiratory tract
Esophago/Gastro
Artheries
2) Reassurance if nothing found
IF ZONE II
UNSTABLE:
1) A, B, C always first!
2) Surgical exploration
Always explore if
musculocutaneus platysma is
affected
IF ZONE II
UNSTABLE:
Musculocutaneus
Platysma
IF ZONE I & III
STABLE:
1) Endoscopy if hoarseness/hematoma:
Respiratory tract
Esophago/Gastro
Artheries
2) Reassurance if nothing found
PROBLEM MISCELANEUS SYMPTOM (CLUES) TEST TREATMENT
Rib Fracture MCC of injury
Elderly
Fall
History
Pain w/ resp.
Hematoma/open
wound
Costochondral
junction middle
and lower ribs
CXR Pain medication
Flail Chest 4 or more ribs
fractured in 2
places
Major trauma
Caves during
respiration and
bulges in
expiration
CXR Anesthesia and rib
blockage, positive
ventilation and high
oxygen (avoid
barotrauma) surgical
stability not required
Cardiac
tamponade
Liquid between
heart and
pericardium, CA
Trauma, URI
Tachycardia
Hypotension
Pulsus paradoxus
JVD
Echocardiogram Pericardiocentesis,
pericardial window
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Pericarditis Inflammation of
pericardium
URI
Friction rub
CXR,
echocardiogram,
EKG, CK MB (rule
out MI), ESR very

high
Treat cause, NSAIDS,
pericardiocentesis,
pericardiostomia
Pleuritis
(Pleuresy)
Inflammation of
pleura
URI, CA, LES, RA,
Irritants (asbestos),
Drugs
Stabbing pain
during inspiration
CBC,
thoracocentesis,
CXR, Chest echo
Treat cause, NSAIDS
Tracheal/
Bronchial
rupture
Violent trauma Trauma, gunshot,
infection, object
Cough w/blood
Gas under need
skin of neck, chest
X-rays, CT scan Object: rigid fiber optic
bronchoscopy to
retrieve object
Others: Surgery
if big plus chest tube w/
suction
Aortic rupture Violent trauma,
deacceleration
Look for wide
mediastinum in
CRX
If CRX not
conclusive and
suspicious is
high, CT scan or
transesophageal
echo
Surgery
Pulmonary
contusion
Violent trauma With flail chest or
rib fracture, but

crackles
CT scan, look for
atelectasia
Fluid restriction and
oxygen. Prolonged
symptoms possible
ARDS
Cardiac
contusion
Violent trauma,
CPR
Abnormalities in
ventricle to
contract
EKG right bundle
branch block)
Sinus tachycardia
Ventricular
dysrhythmia
EKG
Echocardiogram
Supportive
EKG monitorization
Hemothorax Trauma, CA,
thorax surgery
Respiratory failure
TachycardiaAnxiet
y
CXR
Thoracocentesis
Analysis of fluid
Treat the cause
Stabilize, Stop bleeding,
Thoracic tube,
Pneumothorax Trauma
(spontaneus)
Sudden sharp pain
on respiration,
Tachycardia,
cianosis, nasal
flaring, no air
movement
CXR, ABG Treat the cause, drain
gas w/ needle if
emergency and later w/
thoracic tube
Diaphragmatic
rupture
Trauma, only in
left side
Sounds of bowel in
thorax (left) or no
air in left lung
CXR, Barium
swallow
Surgery
Trachea Expansion Breath Sounds Percussion
Tension
Pneumothorax Away
Decreased.
Chest may be fixed
in hyper-expansion
Diminshed or
absent Hyper-resonant
Simple
Pneumothorax Midline Decreased May be diminished
May be hyperresonant. Usually
normal
Haemothorax Midline Decreased Diminished if large.
Normal if small
Dull, especially
posteriorly
Pulmonary
Contusion Midline Normal
Normal. May have
crackles Normal
Lung collapse Towards Decreased May be reduced Normal
PNEUMOTHORAX
CARDIAC TAMPONADE
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AORTIC DISECTION BRONCHIAL RUPTURE
DIAPHRAGMATIC RUPTURE
EXPIRATION INSPIRATION
FLAIL CHEST
ACUTE ABDOMEN: Sudden, severe
abdominal pain that is less than 24
hours in duration
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IMPORTANT POINTS: ALWAYS
1)
2)
3)
4)
5)
NPO to reduce risk of aspiration

NG tube to decompress abdomen
IV hydration/ secure via
Analgesia (meperidine)
Abdominal X-RAY
LOOK FOR CLUES:

1)
2)
3)
4)
5)
6)
How and why of pain, how often

Time of iniciation (cronic or acute)
Localization and Progresion
Irradiation
Scale of pain and type
AGE, GENDER

Appendiscitis Inflamation of
apendix, young
people.
Causes:
Inflamation
Fecalith
Parasite
Trauma
Complication:
peritonitis
First periumbilical
and then iliac
fossa (migration)
Tender Mc.
Burneys point,
Rovsings sign,
Obturator sign,
Psoas sign, fever,
anorexia and
vomit
CBC (infection)
Normally clinical,
and only atypical
cases CT scan or
ultrasound to rule
out ectopic
pregnancy or
pregnant ladies
Laparoscopy,
laparotomy
Cholecystitis Due lith in
cystic duct
leading to stasis
Famous FFFs
Pain after fatty
meals radiate to
shoulder
ALK Phos.
Elevation, CBC,
Ultrasound. Best
diagnosis is CT
scan. HIDA if
suspect and
negative US
If acute: surgery
If septic shock:
percutaneus
drainage
If not acute:
elective surgery
PROBLEM SYMPTOM (CLUE) TEST
Biliary colic Cystic duct blocked. Sharp and constant pain
without fever. Negative Murphy s sign.
LFT WNL. Ultrasound
Cholecystitis Cystic duct blocked with infection. Colicky
brief pain at first, then constant pain in RUQ
with fever caused by E coli, klebsiella,
pseudomonas, B fragilis, enterococcus.
Murphy s sign positive.
Increased AST, ALT, AP,
WBC.
Ultrasound
Choledocholithiasis Common bile duct blocked. Colicky pain.
Jaundice.
Increased bilirubin.
Cholangiogram, ERCP
Cholangitis Infection of entire biliary tract. Charcot s triad.
Jaundice and fever
Increased AST, ALT, AP,
bilirubin. Cholangiogram
DIFFERENTIAL DIAGNOSIS
PROBLEM MISCELANEUS SYMPTOM
(CLUES)
TEST TREATMENT
Pancreatitis P eptic ulcer perforation
A lcohol
N eoplasm
C holelithiasis, C F
R enal Dz
E RCP
A
T
I
T
I
S
norexia
rauma
nfection
oxins: Prils, HIV, ASA
ncinerations
corpion bite
Epigastric pain
radiating to the
back (belt)
Cullens sign:
Periumbilical
Turners sign:
Flanks
High Sens:
Amylase
High Spec:
Lipase
CT Scan
If cyst> 5Cm
Dranaige
If due to
obstruction: ERCP
Pancreatic CA:
Surgery bad prog
Intestinal
Ischemia
Due to Shock, Atrial fib.
Hypercoagulable state
Watershed area SMA and
IMA pancreatic flexure
Bowel
distention, and
bloody diarrhea,
bowel sounds
will be absent
Neutrophilic
leucocitosis (left)
increase amylase.
CT scan Air in
bowel and
inflamation of
watershed area
Surgery
Diverticuliti
s
Older people w/
diverticulosis becames
inflamed and
perforated(bulging of
colon walldue to
weakness) low fiber diet,

family history.
Left Lowe Q pain,
leucocitosis, fever
CT scan, No
enemas or
contrast
First episode: IV
fluids and
antibiotics
Subsequent:
Surgery
Ectopic
Pregnancy
Prior PID Acute L R or L Q
pain, acute,
maybe shock
(rupture)
localized in area.
Vaginal bleeding,
cullen sign
Positive pregnancy
test, Ultrasound
for evidence
laparoscopy and
laparotomy
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PROBLEM MISCELANEUS SYMPTOM
(CLUES)
TEST TREATMENT
Peritonitis Inflamation of peritoneum
due to perforation
Pain, tenderness
and guarding,
rebound
Complication of
rupture of
viscera
CBC leucocitosis
Plain AXR,
edematous
vicerae, air. Lavage
if doubt
Stabilization with
IV liquids, correct
acidosis and
electrolite
imbalance,
Surgery,
antibiotics broad
spectrum
Volvulus Malrotation of midgut, Bowel
obstruction and
distension and
vomitus. No
passage of
gases, intestinal
silence.
Abdominal X-ray,
upper GI series
Surgery, correct
rotation, if
necrosis resection
of portion.
PANCREATITIS
APPENDISCITIS
CHOLECYSTITIS
PERITONITIS
PELVIC FRACTURE:
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PELVIC FRACTURE:
1)
2)
3)
4)
Stabilize patient
Military Antishock Trousers
Fixate externally
If blood loss, Embolize
HAND
HAND:
Sacaphids: Avascular necrosis

Hamate: Rupture of hook, nerve damage
(Ulnar)
HAND:
BOXERS FRACTURE
Tx:
Mild: Immobilize
Severe: Surgery w/ pins
ARM:
ARM:
Tx:
- Alignement
- Analgesia
- Close reduction: No complication, no skin break
- Open reduction: Intra-articular fracture is displaced
ORIF Closed reduction was ineffective
Fracture traverses a cancerous lesion
When prolonged immobility
- Surgery: If artery damage is suspected
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- COMPARMENT SYNDROME:
Due to inflamation of tissues
underneed the skin or fascia
Nerve and circulation compression
OPEN THE AREA!
- COMPARMENT SYNDROME:
- GANGRENE:
Infection due to deep entrance of
bacteria to body (diabetic foot, nail)
AMPUTATION!
- GANGRENE:
- OPEN FRACTURES:
1) Clean the area w/ saline and
pressure
2) Verify if nerves or circulations are
intact
3) If < 6 hours, SUTURE AND REDUCT
IN OR
- OPEN FRACTURES:
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- DISLOCATION OF HIP: Shorten leg,
un-anatomical position.
1) Correct position
2) Emergency Reduction
- DISLOCATION OF HIP:
FEVER:
DAYS Famous W LUIDA CAUSE

DAY 1 WIND LUNGS Pneumonia,
Atelectasis
DAY 3 WATER URINE UTI
DAY 5 WOUND INFECTION S. Aureus
DAY 7 WALK DVT
DAY 10 WONDER WHY Abscess
NEUROLOGICAL:
-Hypoxia
ARDS
Post- anesthesia
-Delirium Tremens
-Water intoxication: HypoNA
HyperNA
NEPHROGENIC:
-Post Surgery Urinary Retention
-Hypovolemia
-Clamping of ureter
ABDOMINAL:
- Paralysis of intestine (Ogilvie Synd)
- Adhesions
- Paralytic Ileus due to Anesthesia
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INFECTION:
1)Find the cause with multiple culture
2) Antibiotic Therapy
Do you understand that ABCs always
is first?
Can you do differential diagnosis?
Do you know what to do first?
Do you have a sequence of thinking?
Do you know basically the treatment?
Are you consistent with your thought
process?
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ANTIBIOTICS ANTIBIOTICS
What is an antibiotic? What is an antibiotic?
An agent that inhibits the growth or multiplication An agent that inhibits the g
rowth or multiplication
of, or kills, of, or kills, a a living organism living organism; usually used in
; usually used in
reference to bacteria or other microorganisms. reference to bacteria or other mi
croorganisms.
Who invented them? Who invented them?
Alexander Fleming, in 1928 is the one who Alexander Fleming, in 1928 is the one
who
purifiedrified PENICILLIN. pu PENICILLIN. THE CAT? THE CAT?
PURE LUCK? PURE LUCK?
Of course not Of course not
Who is the genius? Who is the genius?
OR OR
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BASIC PRINCIPLES BASIC PRINCIPLES
FOR FOR
PHARMACOTHERAPIE PHARMACOTHERAPIE
Learn MOA Learn MOA
Learn SIDE EFFECTS Learn SIDE EFFECTS
Dont kill a mosquito with a gun Dont kill a mosquito with a gun
Cost Cost BenefitsBenefits law law
TYPESYPES OF T OF
ANTIBIOTICS ANTIBIOTICS
Cell Wall Inhibitors Cell Wall Inhibitors
Proteinrotein i Synthesisynthesis h i Inhibitorsnhibitors hibi P i S h i I hibi
P S I P S I
Metabolite Inhibitors Metabolite Inhibitors
Special Function Inhibitors Special Function Inhibitors
CELL WALL INHIBITORS CELL WALL INHIBITORS
1.- 1.- PenicillinPenicillin
- -OxaOxa, , cloxa cloxa dicloxa dicloxa, , nafinafi-- CILLINCILLIN
- - Ticarcillinicarcillin T
- - AztreonamAztreonam
2.- 2.- CephalosporinsCephalosporins
3.- 3.- CarbipenemsCarbipenems
4.- 4.- VancomycinVancomycin
Where do you get the molds? Where do you get the molds?
1.-PENICILLINEPENICILLINE 1.- 1.-PENICILLINEPENICILLINE 1.-
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1.-PENICILLINPENICILLIN 1.1.1.-- Binds to PBP Binds to PBP
2..-- 2 DisruptDisrupt cell wall Disrupt cell wall 2 2 Disrupt cell wall cell wa
ll
3.3.-- Provoke apoptosis Provoke apoptosis
1.-PENICILLINEPENICILLINE 1.1.1.-- Binds to PBP Binds to PBP
1.- 1.- PENICILLINPENICILLIN 1.-PENICILLINPENICILLIN 1.2.2.-- Disrupt cell wall Disrupt cell wall
3.3.-- Provoke apoptosis Provoke apoptosis
1.-PENICILLINEPENICILLINE 1.- 1.-PENICILLINPENICILLIN 1.What does it What does it
kill? kill?
Staph. Staph. AureusAureus
Staph. Staph. EpidirmidisEpidirmidis
BacillusBacillus
Clostridium Clostridium
Staph. Staph. SaprophiticusSaprophiticus
Strep. Strep. Pneumoniaemoniae Pneu
Strep. Strep. Pyogenesenes Pyog
Strep. Strep. SanguisSanguis
Strep. Strep. Mutanstans Mu
Strep. Strep. Agalactiaegalactiae A
Klebsiella Klebsiella
Neisseria Neisseria
CitrobacterCitrobacter
P. P. AuroginosaAuroginosa
H. Influenza B H. Influenza B
Actinomyces Actinomyces israelii israelii
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1.-PENICILLINPENICILLIN 1.Or, if you dont remember: Or, if you dont remember:
GRAMGRAM GRAM + GRAM +
Capsulated bacteria Capsulated bacteria
1.- 1.- PENICILLIN PENICILLIN
Side effects: Side effects:
1.- 1.- Typical: Typical: Anemia, Vomiting, Anemia, Vomiting,

Diarrhea,, Alopecia,, Photosensitivity.. Diarrhea Alopecia Photosensitivity Diar
rhea Alopecia Photosensitivity Diarrhea Alopecia Photosensitivity
2.- 2.- Special:Special: AllergieAllergie
Typical side effects: Typical side effects:
Dueue destructionestruction i fff Rapidlyapidly idldl D d i f R i D to d o R D t
o d o R
dividing cells dividing cells
Resistance:Resistance:
- - Mutate PBP, so drug cannot bind Mutate PBP, so drug cannot bind
Thickercker k branes,ranes, drugrug Thi k b d - - Thi membb so d Thi mem so d
cannot get in cannot get in
- - Mutate or destroy the drug with an Mutate or destroy the drug with an
enzymeenzyme
1.- 1.- PENICILLIN PENICILLIN 1.- 1.- PENICILLIN PENICILLIN
Oxa Oxa, , Cloxa Cloxa, , DicloxaDicloxa, , NafiNafi CILLIN CILLIN
1.- 1.- MOAMOA Same as penicillin Same as penicillin
2.-BULKIER 2.- BULKIER -- R R - -RingRing
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What does it mean? What does it mean?
- - PenicillinasePenicillinase cant bind to cant bind to
the R group for being huge the R group for being huge the R group for being huge
the R group for being huge
so the antibiotic wont get so the antibiotic wont get
deactivated and will attach deactivated and will attach
PBP PBP
What do you kill with them? What do you kill with them?
SStaph.taph. hh Aureusureus A - - S S A A
Can you kill OTHER gram Can you kill OTHER gram
positives and capsulated positives and capsulated
bacteria? bacteria?bacteria? bacteria?
YESYES ! !
Do you kill them w/ Do you kill them w/ NaficillinNaficillin??
NO ! NO !
WHY?WHY?
You could use simple You could use simple
penicillin for that penicillin for that penicillin for that penicillin for that
Dont kill a Mosquito with a gun! Dont kill a Mosquito with a gun!
AMPICILLIN Vs. AMOXICILLIN AMPICILLIN Vs. AMOXICILLIN
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AmpicillinAmpicillin
80% fff drugrug deactivatedeactivated i d iithith h P--450 80% f d d i d i h P 4
50 450 - - 80% o d d w P 80% o d d w P 450
Amoxicillin Amoxicillin
- - GetsGets ACTIVATED with P-450450 ACTIVATED with P1.- 1.- PENICILLIN PENICILLIN
- - Ampicillin: Ampicillin: Adults Adults
- - Amoxicillin: Amoxicillin: Children Children
Liver failure Liver failure
Amoxicillinmoxicillin i illi AA i illi Clavulanicavulanic l i ClCl l i + A + Cl
ac.: ac.:
To inhibit B-LactamaseLactamase To inhibit B1.- 1.- PENICILLIN PENICILLIN
MOA:MOA: SAMEAME MOA S MOA SAME SAME
SIDE EFFECTS: SAME SIDE EFFECTS: SAME
Bugs to kill: Bugs to kill:
Gramram G G + G +
Capsulated bacteria Capsulated bacteria
E. Coli? E. Coli?
Ticarcillin: Ticarcillin:
Too kill PSEUDOMONA T kill PSEUDOMONA T kill PSEUDOMONA T kill PSEUDOMONA
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WHY?WHY?
WHY?WHY?
PPseudomonaseudomona dd iliiss kiiking,king, il k P P i lionon attac i li attac
so you need a big riffle to kill it so you need a big riffle to kill it
SIDE EFFECS: SAME SIDE EFFECS: SAME
AZTREONAM: AZTREONAM:
For GRAM For GRAM
Sameame iinciple:inciple: i l IfIf lddldld killill S i i l l k S pr If you wou kil
l S pr If you wou kill
a Gram+, then use a smaller a Gram+, then use a smaller
weaponweapon
2.- 2.- CEPHALOSPORINS CEPHALOSPORINS 2.- 2.- CEPHALOSPORINS CEPHALOSPORINS
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2.- 2.- CEPHALOSPORINS CEPHALOSPORINS
1st gen
2de gen
+
+
Cephalexin, cefazolin
Cefuroxime, cefotetan g
3th gen
4th gen
+
+
-
Ceftriaxone, cefotaxime
Cefepime
2.- 2.- CEPHALOSPORINS CEPHALOSPORINS
MOA: SAME AS PNC MOA: SAME AS PNC
SIDESIDE EFFECTS:: SAMEAME SIDE EFFECTS S SIDE EFFECTS SAME EFFECTS SAME
2.- 2.- CEPHALOSPORINS CEPHALOSPORINS 2.- 2.- CEPHALOSPORINS CEPHALOSPORINS
3.-CARBAPENEMS 3.- CARBAPENEMS
THIS IS A BAZOOKA FOR THIS IS A BAZOOKA FOR
TERRORISTS TERRORISTS
IMIPENEM/CILASTATIN IMIPENEM/CILASTATIN
- - To inhibit renal To inhibit renal dihidropeptidase dihidropeptidase
MOA: SAME MOA: SAME
$ 450 $ 450 a vial QUID a vial QUID XX 10 days 10 days
4.- 4.- VANCOMYCIN VANCOMYCIN
Inhibits cell wall of ALL GRAM+ Inhibits cell wall of ALL GRAM+
MOA: Inhibit cell wallall MOA: Inhibit cell w
MOA: Inhibit cell wall MOA: Inhibi
t cell wall
mucopeptide mucopeptide formation gen formation gen
D-ala D-ala DD--alaala
Resistance: Resistance: mut. mut. D-alaala D- to D-laclac to D504
10/13/2008
9
4.- 4.- VANCOMYCIN VANCOMYCIN
RED MAN SYNDROME: RED MAN SYNDROME:
- -PretreatPretreat w/ w/ antihistaminicsantihistaminics
LOWER INFUSSION LOWER INFUSSION -LOWERLOWER - INFUSSION INFUSSION
PROTEIN SYNTHESIS PROTEIN SYNTHESIS
INHIBITORS INHIBITORS
A good business: A good business:
BUYBUYBUY
C C
BUY
A A
T T
E E
L L
L L
30s 30s
50s 50s

OR
505
10/13/2008
10
A good business: A good business:
BUYBUYBUY
C C hloramphenichol hloramphenichol
E E rithomycin rithomycin BUY
A A minoglucosides minoglucosides
T T etracyclinsetracyclins
E
(
c
L
E rithomycin rithomycin
(Macrolides) Macrolides)
c L L indamycinindamycin
L inezolidinezolid

Aminoglucosides: Aminoglucosides:
Gentamicin, Gentamicin amikacin,, amikacin streptomycin streptomycin -Gentamicin
Gentamicin - , amikacin amikacin streptomycin streptomycin
-MOA: -MOA: Inhibit Initiation complex Inhibit Initiation complex
-Bactericidal -Bactericidal
-Potentiation -Potentiation w/w/ampicillinampicillin
Aminoglucosides: Aminoglucosides: (CONT.) (CONT.)
SIDE EFFECTS: SAME SIDE EFFECTS: SAME - - SIDE EFFECTS: SAME SIDE EFFECTS: SAME
- - PLUS: PLUS: Ototox Ototox and and Nephrotox Nephrotox
Tetracyclins: Tetracyclins:
-Doxicycycline: -Doxicycycline Lyme, Tularemia, : Lyme, Tularemia,
FrancicellaFrancicellaFrancicella (FecallyFecallyFecallyFecally ( excreted) excr
eted) Francicella ( ( excreted) excreted)
-Minocycline: -Minocycline: Propionebacterium Propionebacterium Acne Acne
(Not even excreted) (Not even excreted)
-Demeclocycline:: -Demeclocycline SIADH (Neprotox)) SIADH (Neprotox
Tetracyclins: Tetracyclins: (CONT.) (CONT.)
MOA:: Inhibitingnhibiting hibi i hee bindingnding di fff MOA I hibi i h bi di f
-MOA - I thh bi o MOA I t bi o
aminoacyl-tRNAtRNA aminoacyl- to the to the mRNA- mRNAribosome ribosome complex.complex.
-Bacteriostatic -Bacteriostatic
506
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11
PROTEIN YNTHESIS PROTEIN YNTHESIS
SIDE EFFECT:: SIDE EFFECT SIDE EFFECT SIDE EFFECT
IMAGINE.Plus: IMAGINE.Plus: Ototox Ototox Nephrotox Nephrotox
Chloramphenichol: Chloramphenichol:
- - MOA: Inhibit peptide bond at 50s MOA: Inhibit peptide bond at 50s
IhibiibinhibitInhibit P--450450 IhI P 450 450 - - P P
- - NOT IN USA NOT IN USA
- - SIDE EFFECTS: SAME SIDE EFFECTS: SAME
Plus: BM Sup. A. Anemia, Plus: BM Sup. A. Anemia, GBSynd. GBSynd.
Erithromycin: Erithromycin: MACROLIDES MACROLIDES
- - Clarithrmomycin Clarithrmomycin, , azithromycin azithromycin
Inhibitnhibit hibiibi llocationlocation i byy ibliblyibly I h l i b ibl - - I tr
ans b revers I trans b revers
binding to 23s portion of 50s. binding to 23s portion of 50s.
- - Bacteriostatic Bacteriostatic
Erithromycin: Erithromycin: MACROLIDES (CONT.) MACROLIDES (CONT.)
- - Tx Tx for: Atypical pneumonia for: Atypical pneumonia
(MycoplasmaMycoplasma)Chlamydia)ChlamydiaMycoplasmaMycoplasma),, ( 2gg,, N.. 2 N
( ( Chlamydia 2g N ) Chlamydia 2g N
Gonorhea Gonorhea 1g.1g. (azithromycin)) (azithromycin
cLindamycin: cLindamycin:
- - MOA: Inhibit elongation factor of MOA: Inhibit elongation factor of
50s 50s 50s 50s

- - Uses: Anaerobes above Uses: Anaerobes above diapragmdiapragm
Plus: (before) No1. for Pseudo. Colitis Plus: (before) No1. for Pseudo. Colitis
Linezolid: Linezolid:
- - MOA: Inhibit initiation of 50s AND MOA: Inhibit initiation of 50s AND
30s 30s 30s 30s
- - MRSA w/ resistance to MRSA w/ resistance to Vanco Vanco
- - DONT USE IT...Like pressing the DONT USE IT...Like pressing the
RED BUTTON RED BUTTON
507
10/13/2008
12
cLindamycin: cLindamycin:
- - MOA: Inhibit elongation factor of MOA: Inhibit elongation factor of
50s 50s 50s 50s
- - Uses: Anaerobes above Uses: Anaerobes above diapragmdiapragm
Plus: (before) No1. for U. Colitis. Plus: (before) No1. for U. Colitis.
METABOLITE METABOLITE
To destroy nucleotides: To destroy nucleotides: To destroy nucleotides: To destr
oy nucleotides:
What is a nucleotide? What is a nucleotide?
To destroy nucleotides: To destroy nucleotides:
S-ADENOSYLADENOSYL--METHIONINENINE S- (SAM) METHIO (SAM)
Methilate Methilate or differentiate the nucleotides or differentiate the nucleot
ides
All of them. All of them.
Except: T (thimidinethimidine)who)whothimidinethimidine),, Except: T ( isis meth
ilated methilated
Except: T ( Except: T ( who is ) who is methilated methilated
by Folic Acid by Folic Acid
508
10/13/2008
13

dUMP dTMP
Thymidylate synthase
5-FU
CH 2-THF DHF
THF DHF reductase
TMX/SMX
OR MTX
TRIMETHOPRIM TRIMETHOPRIM
MOA:MOA: Inhibit DHFHF MOA: Inhibit D MOA: Inhibit DHF Inhibit DHF
Works?....Not at allAlone Works?....Not at allAlone
SULFONAMIDES SULFONAMIDES
MOA: Inhibit MOA: Inhibit Dihydropteroato Dihydropteroato MOA: Inhibit MOA: Inhi
bit Dihydropteroato Dihydropteroato
synthetase synthetase
Works?....Not at allAlone Works?....Not at allAlone
BUT:TMX + SMX BUT:TMX + SMX
Good for: UTI, Prof and Good for: UTI, Prof and txtx of of
Pneumocystis Pneumocystis CariniiCarinii, , ShigellaShigella
and Salmonella. and Salmonella.
METABOLITE
INHIBITORS
METABOLITE
INHIBITORS
METABOLITE
INHIBITORS
METABOLITE
INHIBITORS

Thesameashesameas B99 T B defficiancydefficiancydefficiancy The same as B9 The s
ame as B9 defficiancy
- - Neural pores non-fusionfusion Neural pores non- - Megaloblastic Megaloblastic anemia anemia
- - Kernikterus Kernikterus in neonates in neonates
509
10/13/2008
14
SPECIAL FUNCTION SPECIAL FUNCTION
Topoisomerase
QUINOLONES: QUINOLONES:
MOA:Antitopoisomerase MOA:Antitopoisomerase II II
InhibitInhibit Windinginding-- Inhibit W unwinding unwindingunwinding Inhibit Wi
nding Winding unwinding
NAMES: NAMES:
Cipro Cipro
Levoevo L L L
Gati Gati
Nor Nor
FLOXACINXACIN FLO
SIDE EFFECT: SIDE EFFECT:
Besides typical: Besides typical:
Tendonitisendonitis d i i ddondon T d i i d - - T or ten rupture T or ten ruptur
e
- -MyalgiaMyalgia in kids in kids
METRONIDAZOLE: METRONIDAZOLE:
MOA: Free radicals and toxic MOA: Free radicals and toxic
metabolites formation. metabolites formation.
METRONIDAZOLE: METRONIDAZOLE:
Covers:overs: C Monocelularonocelular l l M l l ites:tes: i C C M M parasiarasi
p
G. G. LambliaLamblia, E. , E. HystoliticaHystolitica, G. , G.
Vaginalis Vaginalis, anaerobes below , anaerobes below
diapragm diapragm. T. . T. TerapieTerapie H.H. Pylori. Pylori.
510
10/13/2008
15
ANTI TB DRUGS ANTI TB DRUGS
R RIFAMPIN: IFAMPIN: MOA:Inhibit MOA:Inhibit
DNA dependent RNA DNA dependent RNA
polymerase,ymerase, meraseerase Crossesrosses BBB.. pol m C BBB pol Crosses BBB
pol Crosses BBB
PROF. TB and N. PROF. TB and N. MenigitidisMenigitidis
SIDE EFFECT: SIDE EFFECT: HepatotoxicHepatotoxic
(Frecuent (Frecuent LFT) LFT)

R RIFAMPIN: IFAMPIN:
Enhances P-450450 Enhances POrange body fluids. Orange body fluids.
E Ethanbutol: thanbutol: MOA: Obstructs MOA: Obstructs
cell wall formation by disrupting cell wall formation by disrupting
arabinogalactan arabinogalactan snthesisthesisynthesis,ynthesis, sns arabinogala
ctan arabinogalactan s
increases permeability of cell increases permeability of cell
wall. wall.
E Ethanbutol: thanbutol:
SIDE EFFECT: SIDE EFFECT:
-Optic -Optic neuritis neuritis
-Red--greengreen -Red color blindness color blindness
-Peripheral -Peripheral neuropathy neuropathy
-Arthtalgia -Arthtalgia
S Streptomycin: treptomycin: Aminoglucoside Aminoglucoside
P Pyrazinamide: yrazinamide: MOA: Stops TB MOA: Stops TB
growth by, growth by, in acid media in acid media, ,
ihibiting ihibitingihibiting enzime enzime fattyy acid fattfatt acid ihibiting e
nzime enzime acid fatt acid
synthetase. synthetase.
SIDE EFFECTS: SIDE EFFECTS: ArthralgiaArthralgia, ,
hepatotoxicity. hepatotoxicity.
511
10/13/2008
16
I Isoniazid: soniazid: MOA: Inhibit MOA: Inhibit
synthesis of synthesis of mycolicmycolic acid. acid.
hancesances h 4050.50. 4044
Enhh P- En PSIDE EFFECTS: SIDE EFFECTS: HemolysHemolys in in
G6PD pts, G6PD pts, hepatotoxicityhepatotoxicity, ,
neurotoxicity that can be neurotoxicity that can be
prevented w/ B6. prevented w/ B6.
ANTIFUNGAL ANTIFUNGAL
THERAPYTHERAPY
Amphotericine Amphotericine B: B:
MOA : Binds to MOA : Binds to ergostyerolergostyerol and and
pokes thehe cell wallall provokingrovoking pokes t cell w p pokes the cell wall
provoking pokes the cell wall provoking
leakage of leakage of electrolites. electrolites.
THERAPYTHERAPY
THERAPYTHERAPY
Amphotericine Amphotericine B: B:
Used in systemic mycosis Used in systemic mycosis
SIDE EFFECTS:: Hypotension,ypotension, i SIDE EFFECTS H i
SIDE EFFECTS H SIDE EF
FECTS H
fever and chills, fever and chills, flebitisflebitis ifif IV IV
THERAPYTHERAPY
Nystatin Nystatin: Same as : Same as AmphotericineAmphotericine B B
SIDE EFFECTS:: Onlynly l ddd SIDE EFFECTS O l d l l SIDE EFFECTS O use SIDE EFFE
CTS O use topycall topyca
for being very toxic. for being very toxic.
THERAPYTHERAPY
Nystatin: Nystatin: SWISH AND SWALOW SWISH AND SWALOW
For oral For oral candidiasis. candidiasis.
512
10/13/2008
17
THERAPYTHERAPY
Caspofungin Caspofungin: Disturb integrity of : Disturb integrity of
Cell Wall Disruption. Cell Wall Disruption.
Indication: Indication:Indication: Aparagillosis Aparagillosis Indication: Apara
gillosis Aparagillosis
Side effects: Increase Side effects: Increase CreaCrea, ,
hypokalemia, hypokalemia, hypersensitivity hypersensitivity
THERAPYTHERAPY
Caspofungin: Caspofungin:
THERAPYTHERAPY
Azoles:Azoles:
-Flucon -Flucon
Ketoconetocon K -KK -Itracon -Itracon
THERAPYTHERAPY
Azo Azo LE LE s s: :
MOA: Prevent conversion of MOA: Prevent conversion of
L L anosterol anosterolanosterol tototo E E rgosterol rgosterolrgosterol byby L
L anosterol to E E rgosterol by by
inhibiting fungal P-450.450. inhibiting fungal PFUNGISTATIC! FUNGISTATIC!
THERAPYTHERAPY
Terbinafine: Terbinafine:
MOA: Inhibit MOA: Inhibit Squalen Squalen epoxidaseepoxidase
USESUSES:: Oinicomycosisnicomycosis i Oi i USES USES O O
Bad cases: ORAL Bad cases: ORAL
THERAPYTHERAPY
AZOLES AND TERBINAFINE AZOLES AND TERBINAFINE
Azoles
Terbinafine
513
10/13/2008
18
THERAPYTHERAPY
FlucytosineFlucytosine::
MOA: MOA: 1) Inhibit microtubules 1) Inhibit microtubules
2) Inhibit 5-FUFU 2) Inhibit 5Consequence: Inhibit DNA Consequence: Inhibit DNA SyntSynt
THERAPYTHERAPY
FlucytosineFlucytosine::
Side Side effecseffecs:: Typical very strong Typical very strong
Plus: Hallucinations, Plus: Hallucinations, psycosis psycosis, ,
peripheral peripheral neuropathieneuropathie. .
THERAPYTHERAPY
IN ONE GRAPH: IN ONE GRAPH:
514
10/13/2008
1
Biochemistry
Glycolysis, Gluconeogenesis
&TCA
Mong-Khanh Le, M.D.
Objective
Glycolysis
Sucrose metabolism
Lactose metabolism
Gluconeogenesis
TriCarboxylic Acid Cycle (TCA)
Focus
Naming enzymes
Where it happens: cytosol vs mitochondria
energy usage and production
Regulations
Clinical significant Dzs
Connections!!!! AS ALWAYS
Why Glycolysis?
Most used pathway in body
Turn food into energy
Start w/ Glu, Lactose, Fructose
Simple Vs Complex Carbo Simple Vs Complex Carbo
Substrate = Glu and production = pyruvate
In cytosol (what does not have Mito will
depend solely on it for ATP!!!!)
Organ effected: RBC, B>>H>>K
What is in our diet
USDA % in Diet Converting
in Calorie
Pathways
Carbohydrate 55% 4Kcal/g Glycolysis
Ptrotein i 15% 4Kcal/g l/ TCAA, Urea P 15% 4K TC U
Lipid 30%(<10
% sat)
9Kcal/g FAsyn, Boxidation
Alc ?????? 7Kcal/g TCA,
Lactate
Name Enzymes Review
Substrate=1st name
What was done to substrate= 2nd part or
last t l name
515
10/13/2008
2
Name Enz (cont)- Move around
Isomerase= create isomer, think Fructose
and Glucose
Epimerase= make epimer, differs around 1
chiral C (glu galactose) chiral C (glu galactose)
Mutase= move P fr one C to another C

Transferase= move sidechain fr 1
substrate to another (interchain)
Name Enz (cont)-Add stuff
Kinase= use ATP to add P, Mg cofactor.
Phosphorylase=Use free P adding to
substrate.
Carboxylase=ylase uses CO2 to add C, uses Carbox uses CO2 to add C uses
ATP and Biotin.
Synthase= 2 substrates consumed in
reaction, named after product.
Synthetase= 2 substrates consumed.
Need ATP
Name Enz (cont)-remove stuff
Dehydrogenase= take out H+ with
coFactor (ie. Tender Loving Care For
Nancy).
Phosphatase= breaks phosphate bond Phosphatase= breaks phosphate bond
Hydrolase= break a bond with H2O
Lyase= cut C-C bond with cofactor
Thio= breaks S bond
B-compx
Tender Loving Care For Nancy.
PLAN F.
Dzs.
Glycolysis
Substrates=Glu and end products of
Sucrose and Lactose pathways (also fr
glycerol)
Final product: Pyruvateruvate Final product: Py
9 steps
3 irrversible steps= Exclusive glycolysis
Triangle at mid way (4th reaction)
Glu Transport
GLU 1 & 3: basal uptake most cells.
GLU 2: Storage (liver); Glucose sensor (Bislet)
GLU-4: 4 increase by INSULIN in fat t dd GLU i b INSULIN i f an
muscle. Increase in exercising skeletal
muscle. (Fat, skeletal and heart)
516
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3
Glycolysis Glycolysis Regulations
HK: Most Tissues, low Km= works both in

fed and fast. Inhibited by its own product,
G-6-P.
GK: Liver only, High Km=works during fed
only. +++ by insulin
Why Glu has to be phospholation?
PFK-1
Rate Limiting Step
Stimulated by: AMP, F-2,6-BP, Insulin
(FIA) (FIA)
Inhibited by: Citrate, ATP, PEP, Glucagon,
Acidosis (the GA CAP).
PKF-2
Fruct-6-P to F-2,6BP fed state

F-2,6BP to Fruct-6-P fast state
Increases glycolysis
Decreases gluconeogenesis
Stimulated by Insulin
Inhibited by Glucagon
PK
Stimulated by: F1,6-P, Insulin (FI)
Inhibited by: Glucagon, Alanine, Inhibited by: Glucagon Alanine
cAMP, ATP, AcetylCoA (GA AAA)
Glycolysis Regulations Recap
Enzymes Stimulated Inhibited Comments
HK G6P
PFK-1 *AMP
*F-2,6-P
Citrate, ATP
PEP, Glucagon,
RLS
*Insulin lowPH
Pyruvate
Kinase
*F1,6-P(feed
forward
pos=only
one in
Biochem)
*Insulin
Alanine,
Glucagon,
cAMP, ATP,
AcetylCoA
517
10/13/2008
4
Glycolysis Dz=Chronic Hemolysis
Chronic Hemolysis dt RBC lacks of energy fr
glycolysis.
PK Def. leads to elev 1,3BPG, which can
convert to 2,3BPG.
Oxygen hift to R (incr Km, decr O curve shift t R (i K d
Affinity).
Also elevate other glycolytic intermediates in
RBC (inhibition to many steps)
No Heinz bodies
AR
Glycolysis Dz: MODY
Mature Onset Diabetes of the Young:
Liver (= GK)
Glucokinase mutations leads slow down
lycolysis. l i Plasma Glu increased. d gl Pl Gl i
Other Glycolysis Dz
Arsenate inhibits Glyceraldehyde-3-P
dehydrogenase
Fluoride id inhibits hibit Enolase: l Shiny hite Fl i E Shi whit
teeth
Other Glycolysis Dz
Phosphoglycerate kinase inhibited:
increase 1,3-BPG, which converted to 2,3BPG by RBC mutase decrease Hb
affinitivee for O2 (shift to R, incre Km) affinitiv for O2 (shift to R incre Km)
Other Glycolysis Dz
Glyceraldehyde-3-P: has disulfide bonds
which can be disrupted by Alc.
Also Mercury can inhibit sulfur group of
(brain, i lung, kidney) ) enzyme (b l kid
Other Glycolysis Dz
ANY glycolysis enz def= HEMOLYSIS
518
10/13/2008
5
Glycolysis Connections
In anaerobic state, production of lactate

and NADH reoxidized back to NAD+.
In RBC (no mitochrondria) turns to LDH
solution Lactate pathwayay. solution Lactate pathw
What are 3 enz exclusively from
glycolysis?
Net fr 1 Glu= 2 pyruvate + 2ATP +2NADH
Sucrose/Fructose Metabolism
Fruits
3 reactions
End products: Glu, DHAP, GA3P
Continues with Glycolysis after trio Rx
Fructose Fructosuria
Essential Fructosuria: FructoKinase Defpolydipsia, polyuria, and UTI. BENIGN.
Fructose Intolerance: Aldolasee B def.- Fructose Intolerance: Aldolas B def.
fructosuria, liver and proximal renal tubular
disorder.
When Fruc-1-P accumulated, it inhibits Glu
production causing severe Hypoglycemia.
Point Upon Wonder
Why Fructose Intolerant Pt has
hypoglycemia when we give them
fructose?
Why DM can eat fruit withoutithout increase Why DM can eat fruit w increase
their plasma Glu?
Why diet people can eat lots of fruit w/o
gain wt?
Lactose/Galactose
519
10/13/2008
6
Galactose Recap
End with: Glu-1-P and Glu. Both feed into
Glycolysis
Uses 1ATP
4 titions 4 reac
Enzymes: lactase, GK, G-1-P UT
Lactose Intolerant
Latase Defieciency
Osmotic diarrhea
Bloated, pain
Rx: Avoid Soy milk or Latase added
milk.
Type 1 Galactosuria
Type 1 (Non Classical)
Galactokinase def.
Galactosemia<< galactosuria (polydip &
lyuria i ithith UTI!!!!). pol w UTI!!!!)
Excess converted to Galactitol via aldose
reductase causes cataract.
Rx: avoid
Type 2 Galactosemia
Type 2 (Classical) Galactosemia
Gal-1-P Uridyl transferase Def.
Increase Gal-1-P will inhibits P-Glu Mutase,
which interferes with glycogen syn and
degradation d ti Hypoglycemic l i d H .
Excess converted to Galactitol via aldose
reductase causes cataract.
More severe addition to above. Vomit/diarrhea/
liver/ lethragy/ MR.
Rx: avoid
Clinic Test
Glu has OH which can be reduced for a
positive test in cases of excess Glu
Galactosuria and Fructosuria are urine pos
test test
If stool pos test = malasorption, osmotic
diarrhea or inflammation
Also called reducing substance
Galactose Connections
Babies need a lot of milk (rich lactose)
because of baby uncoupling its ECT.
UDP-Gal can reenter the pathways
If lactose intolerant: Soy milk
520
10/13/2008
7
Point upon wonder
Why galactosemia Type 2 pt has
hypoglycemia when we give them lactose?
Comparing i Galactose, l t hhy Fructose t C G w F can
be given to baby at 6 months?
Gluconeogenesis
A de novo synthesis of Glu from 3C and
4C precusors.
4 irreversible steps
In both Mitochondria and Cytoplasmtoplasm. In both Mitochondria and Cy
Occur during fasting state, glycogen
depleted.
Mainly in Liver, Kindney, Adrenal Cortex
and intestinal epithelilium.
Provide Glu to brain and RBC.
Gluconeogenesis
Substrates are:
glucogenic aa (protein fr muscle)
Lactate (fr RBC and anaerobic exercise)
Glycerol 3 P (fr adipose tissue/
triacylglycerol)
Product: Glu
Regulation of Glyconeo.
Pyruvate carboxylase
=RLS*******
+ Acetyl CoA *Anapleurotic enz.
*Biotin
*mitochodria
PEPCK + Glucagon
+ Cortisol
*GTP
*cytosol
F 1,6- BisPtase + ATP
-AMP
- F-2,6-BP (fr PFK2)
*Cytosol
* inhibited by insulin,
stim by glucagon.
G6Ptase *In ER; liver only.
(other tissue Glu with P
grp prevent Glu exit cell)
Gluconeogenesis Von Gierke: G6Ptase deficiency
severe fasting hypoglycemia

Lactic acidosis
HyperLipidemia
Hyperuremia
short stature
521
10/13/2008
8
Malate shuttle
To bring NADH (product fr glycolysis) into
mitochondria/ETC
Tbo iing OAA (fr tte OAA) itnto T br OAA (f pyruva OAA) i
cytosol for gluconeogenesis
Malate shuttle
Viral Hepatitis vs. Alc Hepatitis
Viral = lyses/ effects cell membrane
AST to ALT is 1:1
Alc = Lyses/effects cell mb and
mitochondria mb
AST to ALT is 2:1
Pyruvate D.H. Complex
Pyruvate Acetyl CoA (Pyr D.H./ B
complex)
Pyruvate t OAA (PC is in itochondria h d i P OAA (PC i i mit
matrix, not in muscle)
Inhibited by: ATP, NADH, Acetyl CoA
B complex=PLAN F
B1= TTP- decarboxylase

B5=Lipoic acid- accepts acetyl grp
B4=CoA- final acetyl aceptor
B3=NAD- oxidizes FADH2 NADH
B2=FAD- oxidizes Lipoic acid FADH2
DZs!!!!!!
Why TCA???
Intermediates in fasting/ liver Glu
Intermediates in fed Fatty Acid
Intermediates also use for syn AA or
converting one AA to another
Potentiate ATP product per Glu eat in!!!
522
10/13/2008
9
TCA
In mitochondria
Cindy Is Kind So She Feeds Many
Ohrphans O
4 irreversible steps
TCA
TCA Regulation
Enzymes Stimulated
by
Inhibited by Comments
Citrate
Synthase
ATP
Isocitrate
D.H.
ADP ATP
NADH
Major RLS
Alpha KG
D.H.
Succinyl CoA
ATP
NADH
B complex
RLS
Link to other pathways
Malate Gluconeogenesis
Citrate FA synthesis
Oxaloacetate and Alpha-KG AA
thesis i (Glutamate/GABA!!!!) t t /GABA!!!!) synth (Gl
Succinyl CoA Heme Synthesis
Fumarate urea cycle
Alpha KG all transaminases AST & ALT
TCA Recap
In mitochondria= aerobic
Substrate: 1 Acetyl CoA + 3NAD + FAD
GDP Pi +GDP + Pi
Product: 2 CO2 + 3NADH + FADH2 +GTP
+ CoA
Net of 1 cycle of 1 Acetyl CoA= 12 ATPs
TCA Connections
No specific Dzs
Problem with TCA is a major low energy
state
NATPo N ATP
No Glu, AA, FA
No intermediates to other linked
pathways
523
10/13/2008
10
Summary 5 pathways
524
525
526
527
528

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cranium, not enough space to cause

-Bleeding between dura mater and

- After ABCs finish PE w/ Glasgow

out MI), ESR very

rib fracture, but

NPO to reduce risk of aspiration

LOOK FOR CLUES:

How and why of pain, how often

PROBLEM MISCELANEUS SYMPTOM (CLUES) TEST TREATMENT

weakness) low fiber diet,

Sacaphids: Avascular necrosis

DAYS Famous W LUIDA CAUSE

1.- 1.- Typical: Typical: Anemia, Vomiting, Anemia, Vomiting,

PROTEIN SYNTHESIS PROTEIN SYNTHESIS

PROTEIN SYNTHESIS PROTEIN SYNTHESIS

50s 50s 50s 50s

To destroy nucleotides: To destroy nucleotides:

SIDE EFFECTS: SAME SIDE EFFECTS: SAME

(Frecuent (Frecuent LFT) LFT)

Mutase= move P fr one C to another C

HK: Most Tissues, low Km= works both in

Fruct-6-P to F-2,6BP fed state

In anaerobic state, production of lactate

severe fasting hypoglycemia

B1= TTP- decarboxylase

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