case 2: acute pancreatitis Flashcards

1
Q

blood - plasma

A
  • Fluid portion of the blood, 55% of blood volume
  • Dissolved ions – Na+ (major) and others
  • Plasma proteins (7-9%, gm/dl) -> colloid osmotic pressure (P) (direct relationship)
    – Albumins – ~60%, produced by the liver, mainly for colloid osmotic
    P and buffering blood pH
    – Globulins – α & β globulins (produced by liver, transport of lipids &
    fat-soluble vitamins; γ globulins (immunoglobulins)
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2
Q

Blood – Formed Elements

A
  • RBC (erythrocytes) – flattened
    biconcave discs
    – Hemoglobin (Hb) – O2 & CO2
    – No nuclei, no mitochondria
    – Produce 300 x 109 RBCs each day
    – ♂ – 5.1-5.8; ♀ – 4.3-5.2 (106/mm3)
  • Buffy coat – platelets & WBC
  • WBC - body defense and immunity
    – Granulocytes – eosinophils, basophils (fewest); neutrophils
    (polymorphonuclear, PMN; 50-70% WBC)
    – Agranulocytes – monocytes & lymphocytes (immune)
  • Thrombocytes (platelets) (not WBC) – fragments of megakaryocytes
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3
Q

Leukocytosis & Left Shift

A
  • WBC = 16.1K with left shift (normal = 4.0-10.9K)
  • Neutrophils – Left vs. Right Shift
    – Organ of origin is bone marrow
    – Lifespan – hours (infection present) to ~2 weeks (no infection)
  • first line of defense

*increase in WBC = infection/inflammation, bacteria infection
*decrease in WBC (leukopenia) = viral infection
*left shift in neutrophils = young, singular large nucleus morphing to/from semilunar shape
* right shift/normal neutrophil = older, 3-5 lobes (leaflets)

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4
Q

What is the relationship between high respiratory rate (R.R.)
(20/min; normal 12-16) and the low O2 saturation rate (88%)?

A
  • breathing shallow = not a lot of O2 into lungs
  • smoking
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5
Q

Does the O2 saturation rate (88%) cause hypoxemia and hypoxia?

A

hypoxemia = lower O2 amount in blood
hypoxia = lower O2 for body’s need

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6
Q

Forms of O2 Transport

A
  • O2 is transported in the blood in two forms:
    – Dissolved form in plasma – directly responsible for PO2 in blood
    – Combined with hemoglobin (Hb-O2) (oxyhemoglobin) in RBC – O2 bound to Hb, does not
    contribute to PO2
  • Loading and unloading of the blood O2
  • This is a sequential process – O2 molecules are dissolved first, the
    dissolved O2 diffuse to RBC, then bind to Hb

Dissolved O2 in blood
plasma (generates PO2)

(Hb-O2 does not generates PO2)

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7
Q

Dissolved O2 in Blood Plasma

A
  • The solubility of O2 = 0.003 ml/dl
    blood/mmHg (each 100 cc of blood/mmHg only dissolves .003 ml of O2, O2 not very soluble in blood plasma compared with CO2)
  • How much O2 is dissolved in the
    systemic arterial blood plasma if
    PaO2 is 100 mm Hg?
    – What is the PO2 in the systemic
    arterial blood (PaO2)?
    – Amount of O2 dissolved in plasma =
    Solubility (ml/dl blood/mm Hg) x
    PaO2
    – = .003 ml /dl blood/mm Hg x 100
    mm Hg = .3 ml O2/dl blood
  • How much O2 is dissolved in the
    systemic venous blood if the PvO2 is
    40 mmHg?
    .003 x 40 = .12 ml O2/dl blood

*100 mmHg in O2 blood
*40 mmHg in deO2 blood

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8
Q

O2 Capacity (O2 Carrying Capacity )

A
  • O2 capacity is the maximal (theoretical) amount of O2 bound to Hb (100% saturation, every molecule of Hb bound to O2)
    – Each gm of functional Hb binds 1.34 ml ml O2 (1.34 ml / gm Hb)
    – O2 capacity only depends on Hb concentration in the blood, higher the gm = higher O2 capacity
    – O2 capacity (ml/dl blood) = (gm Hb/dl blood) x (1.34 ml O2/gm Hb)
  • What is the normal hemoglobin concentration?
    – Men – 13.5-17.5 gm/dl; Women – 12.0-15.5 gm/dl. Why? males secrete testosterone which stimulates production of Hb

– What is the O2 capacity in patients with anemia? Hb reduced, so O2 reduced.
Polycythemia? Hb high so O2 high but the disadvantage is it increases workload on the heart
– What is the advantage and disadvantage for having high or low O2 capacity ?
high O2 capacity means a more O2 for various needs like metabolic or athletic activity, low O2 capacity means person cannot sustain strenuous activity for long periods of time

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9
Q

Hb Saturation Rate

A
  • Hb saturation rate depends on
    PO2
  • Physiologically, Hb saturation
    rate will never be able to reach
    100%
  • Hb is not fully saturated at 100
    mmHg PO2 but rather at ~97%
    saturation
  • As blood leaves peripheral
    tissues after gas exchange, PO2
    is 40 mmHg; Hb is ~ 75%
    saturated

fresh air = higher PO2 in air, more O2 exchange into blood, 95-100 PO2 mmHg ( but after unloading, reduced to 40)

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10
Q

O2 Content

A
  • O2 content (O2 concentration) is the total, actual amount of O2 in the blood
    (plasma & RBC together)
  • O2 content = dissolved O2 + O2 bound with Hb
    – Dissolved O2 = (PO2 x solubility of O2 in blood)
    – O2 bound with Hb = O2 capacity (ml/dl blood) x saturation rate (%)
  • O2 content of a normal subject (PaO2 = 100 mmHg; [Hb] = 15 gm/dl blood):
    – The solubility of O2 in plasma is 0.003 ml O2/mmHg/dl blood -> the amount of
    dissolved O2 = 0.003 ml O2/mmHg/dl blood x 100 mmHg = 0.3 ml/dl blood
    – Hb-O2 = 1.34 ml/gm Hb x 15 gm x 97% = 19.5 ml/dl arterial blood (venous blood = 75%)
    – O2 content = 0.3 ml (dissolved O2) + 19.5 ml (Hb-O2) = 19.8 ml/dl blood
    – % of dissolved O2 accounts for 0.3 ml/19.8 ml x 100 = 1.5%
    – -> > 98% of O2 transported in the blood is in Hb-O2 form
  • Relationship between dissolved O2 and Hb-O2
    – Dissolved O2 accounts for < 2% of O2 content, yet O2 needs to be dissolved in
    the plasma first to be transported into RBC to form Hb-O2, i.e. O2 used for
    binding with Hb is from the dissolved form
  • higher pressure = more o2 dissolved in blood plasma
  • o2 dissolved more readily than co2
  • amount dissolved o2 depends on o2 solubility in blood
  • pressure higher in systemic arterial blood than venous bc pco2 in arterial is higher. more o2 in systemic arterial blood. unloading o2 reduces pco2 and extra amount o2 present in Hb = o2 capacity x saturation rate
  • venous blood o2 capacity = 75%
  • arterial blood O2 capacity = 97%
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11
Q

Hb-O2 Dissociation Curve

A
  • X-axis denotes PO2 (mm Hg), Y-axis denotes O2 saturation rate (%) or
    O2 content (ml O2 /dl blood)
  • (Left panel) -> The higher the PO2, the higher Hb-O2 saturation rate
  • (Right panel) -> The curve of “total” and the curve of Hb-bound almost
    overlap, why?
    greater than 98% of O2 transported in the blood of O2 content is bc of O2 saturation bound to Hb
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12
Q

Volume of O2 Unloaded to Tissues

A
  • O2 content of a normal subject (PaO2 = 100 mmHg; [Hb] = 15 g/dl blood):
    – O2 content in arterial blood = 0.3 ml dissolved + 19.5 ml in Hb = 19.8 ml/dl
    – O2 content in venous blood = 0.12 ml dissolved + 15.1 ml in Hb = 15.2 ml/dl
    – O2 content unloaded to the peripheral tissues = 19.8 -15.2 = 4.6 ml/dl blood
  • O2 content of this patient (PaO2 = 100 mmHg; [Hb] = 15 g/dl blood):
    – Hb-O2 = 1.34 ml/gm Hb x 15 gm x 88% = 17.7 ml/dl arterial blood
    – O2 content in arterial blood = 0.3 ml dissolved + 17.7 ml in Hb = 18.0 ml/dl
    – O2 content in venous blood = 0.12 ml dissolved + 15.1 ml in Hb = 15.2 ml/dl
    – O2 content unloaded to the peripheral tissues = 18.0 -15.2 = 2.8 ml/dl blood
    – 2.8 ml/4.6 ml = 61% of O2 unloading amount, compared with the normal
  • Does the O2 saturation rate (88%) cause hypoxemia and hypoxia?
    – Yes, 61% of O2 normal unloading amount results in hypoxemia and hypoxia

cyanosis

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13
Q

Volume of O2 Unloaded to Tissues

A
  • O2 content of a normal subject (PaO2 = 100 mmHg; [Hb] = 15 g/dl blood):
    – O2 content in arterial blood = 0.3 ml dissolved + 19.5 ml in Hb = 19.8 ml/dl
    – O2 content in venous blood = 0.12 ml dissolved + 15.1 ml in Hb = 15.2 ml/dl
    – O2 content unloaded to the peripheral tissues = 19.8 -15.2 = 4.6 ml/dl blood
  • O2 content of this patient (PaO2 = 100 mmHg; [Hb] = 15 g/dl blood):
    – Hb-O2 = 1.34 ml/gm Hb x 15 gm x 88% = 17.7 ml/dl arterial blood
    – O2 content in arterial blood = 0.3 ml dissolved + 17.7 ml in Hb = 18.0 ml/dl
    – O2 content in venous blood = 0.12 ml dissolved + 15.1 ml in Hb = 15.2 ml/dl
    – O2 content unloaded to the peripheral tissues = 18.0 -15.2 = 2.8 ml/dl blood
    – 2.8 ml/4.6 ml = 61% of O2 unloading amount, compared with the normal
  • Does the O2 saturation rate (88%) cause hypoxemia and hypoxia?
    – Yes, 61% of O2 normal unloading amount results in hypoxemia and hypoxia

cyanosis

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14
Q

Amylase and Lipase Tests

A
  • Amylase
    – For digestion of starch (polysaccharides) into disaccharides
    (maltose)
    – Sources of amylase – saliva, pancreas & others (muscle, liver etc.)
  • Lipase (pancreatic lipase)
    – For digestion of triacylglycerol (triglyceride, neutral fat) into
    monoacylglycerol & fatty acids
    – Sources of lipase – pancreas (main) & stomach
  • Pancreatitis, commonly causes high levels of amylase and lipase
    in the bloodstream
    Amylase and Lipase Tests
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15
Q

Liver Enzymes – ALT & AST

A
  • ALT & AST – screen hepatocellular injury
    – ALT (alanine transaminase, or serum glutamate-pyruvate
    transaminase, SGPT)
    – AST (aspartate transaminase, or glutamate-oxaloacetate
    transaminase, SGOT)
  • AST/ALT ratio – [AST] in blood/ [ALT] in blood
    – Very useful to differentiate causes of liver damage
    – ALT is liver specific, AST is present in multiple organs
    – An AST/ALT ratio of 2:1 or greater indicate alcoholic liver disease
    Liver Enzymes – ALT & AST

present in liver and muscle

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16
Q

The Pyruvate-Alanine Cycle – Liver

A
  • In skeletal muscle, ALT converts
    pyruvate -> alanine:
    – When muscle cells degrade amino
    acids for energy needs, the resulting
    amino group (NH2) is transaminated to
    pyruvate to form alanine -> alanine is
    transported via blood to liver
    – Used as a mechanism for skeletal
    muscle to eliminate NH2 while
    replenishing its energy
  • In liver, ALT converts alanine back to
    pyruvate for:
    – 1. Gluconeogenesis – pyruvate ->
    glucose -> blood -> muscle
    – 2. NH2 is transported from the muscle
    to liver in the form of alanine ->
    converted to urea in the urea cycle ->
    urine excretion
    The Pyruvate-Alanine Cycle – Liver
17
Q

Adrenal Hormones and Stress

A
  • Medulla – secretes epinephrine &
    norepinephrine
    – Fight or flight (sympathetic, short-
    term stress) -> need glucose for
    CNS & skeletal muscle
    – increase Glycogenolysis -> hyperglycemia
    – increase Lipolysis – glucagon-like effects
    – Second messenger – cAMP
    (similar to glucagon)
  • Cortex – secretes glucocorticoids (e.g. cortisol)
    – Long-term stress -> increase hypothalamic CRH -> increase pituitary ACTH -> increase glucocorticoids secretion
    – increase Glucagon secretion -> glycogenolysis -> hyperglycemia
    – increase Lipolysis, ketogenesis & hyperketoemia
    – increase Protein breakdown, gluconeogenesis -> hyperglycemia &
    general weakness
18
Q

Pancreas

A
  • Endocrine – islets of Langerhans
    secrete insulin and glucagon
  • Exocrine glands (> 80%) –
    secrete pancreatic juice (combo of H20 and HCO3-)
    – Acinar cells – secrete enzymes
    (functions?) digestion of food
    – Ductal cells – secrete HCO3- &
    water (functions?) neutralize acidic chyme and secrete into lumen of small intestine
    – Most pancreatic enzymes are
    produced as inactive
    proenzymes, packed in
    zymogens
    – Exocrine secretion stimulated by
    secretin (HCO3-) and
    cholecystokinin (CCK,
    pancreatic digestive enzymes)
19
Q

Gastrointestinal Hormones

A
  • The gastroenteropancreatic (GEP) endocrine cells – some GI
    epithelial cells secrete hormones (blood-borne & ductless)
  • GI hormones – gastrin (stomach); cholecystokinin, secretin, GIP
    (small intestine); GLP-1 (ileum & large intestine)
    satiety
20
Q

secretin

A
  • Secretin – produced mainly by GEP
    cells in the small intestine
  • Stimulus for release – acidic content in
    duodenum; fat
  • Functions – help digesting food in
    duodenum
    – (+) Pancreatic and biliary secretion of
    HCO3-
    – (+) Indirectly effect - potentiating CCK
    activity
    – (-) Gastrin release from G cells
    – Anti-gastrin effects on stomach motility,
    acid secretion
    – (+) Release of pepsinogen, and mucus
    secretion from small intestine
21
Q

Cholecystokinin (CCK; Pancreozymin)

A
  • CCK – produced mainly by GEP cells in the
    small intestine
  • Stimuli for release – fat, protein & acid
  • Functions
    – Cholecystokinin effect – (+) contraction of the
    gall bladder and relaxation of Sphincter of
    Oddi for bile release
    – Pancreozymin effect – (+) pancreatic secretion
    of digestive enzymes
    – Indirectly effect – enhances pancreatic HCO3
    -
    secretion by potentiating the stimulatory action
    of secretin
    – Inhibits gastric emptying – so fatty meals
    move more slowly than nonfat meals
    – Produces satiety to food
  • protect gall bladder?
22
Q

Pancreatitis

A
  • Pancreatitis – an inflammatory process in which pancreatic
    enzymes autodigest the glands
  • Acute pancreatitis – presents with abdominal pain, is usually
    associated with increase blood or urine levels of pancreatic enzymes
  • Chronic pancreatitis – inflammation recurs intermittently -> functional & morphologic loss of the glands
23
Q

Protection Mechanism – Acinar Cells

A
    1. Prevention of auto-digestion – pancreatic enzymes are
      synthesized, stored and secreted in inactive form (proenzymes)
      – Examples – trypsinogen, chymotrypsinogen, proelastase,
      procarboxypeptidase, prophospholipase
    1. The proenzymes are packed in the zymogen granules
      – Zymogen granules contain trypsin (protease) inhibitors and are low in
      pH & [Ca+2] to prevent premature activation until after reaching the
      duodenal lumen
24
Q

Protection Mechanism – Enterokinase

A
  • Duodenal enterocytes produce enterokinase -> attach to the apical membrane -> cleaves N-terminal hexapeptide of trypsinogen -> trypsin (bioactive)
    – Trypsin converts other pancreatic proenzymes into bioactive enzymes
25
Q

Pathogenesis of Acute Pancreatitis

A
  • Cellular protections by factors are out of
    balance -> initiates process -> pancreatitis
    – Extracellular factors – neural (sympathetic, stress) or vascular (ischemia)
    – Intracellular factors – increase [Ca+2], activation of trypsinogen or activation of heat shock protein (can be produced by almost all cells in body when there’s a stress condition
    – Ductal injury -> delays enzymatic secretion
  • -> cellular membrane trafficking becomes
    chaotic -> inside acinar cells
    – 1. -> Fusion of lysosomal (cathepsins) &
    zymogen granules -> activation of trypsinogen
    -> activation of enzymes in the entire zymogen
    granules -> damage of pancreatic tissues
    – 2. -> Inflammation -> neutrophils & macrophage
    infiltration -> increase superoxide & proteolytic
    enzymes (cathepsins) -> pancreatic necrosis,
    edema or hemorrhage
26
Q

Cathepsins and Pancreatitis

A

Once trypsin is activated by cathepsins, it can catalyze the
activation of other digestive proenzymes & trypsinogen ->
autodigestion of the gland

27
Q

Serum Lipase & Amylase

A
  • Amylase and lipase secreted in active form
  • Elevated serum amylase and lipase seen in pancreatitis
  • Serum lipase – high sensitivity and specificity
    – The primary diagnostic marker for acute pancreatitis
    – Rises early in pancreatitis, remains elevated for days
  • Serum amylase
    – Serum amylase – pancreatic amylase & salivary amylase
    – Increases during acute pancreatitis from pancreatic leakage
    – Hyperamylasemia has insufficient specificity:
  • Many disorders cause mild to moderate hyperamylasemia
  • An amylase level > 3X above normal is highly specific for
    pancreatitis
28
Q

Acute Pancreatitis – Etiology

A
  • Insults – alcohol, stone & others
    – -> Zymogen activation (trypsin, chymotrypsin, elastase etc.)
    – -> Pancreatic parenchymal injury (i.e. necrosis & apoptosis)
    – -> Production of cytokines, chemokines, and neurogenic factors (e.g.
    substance P) -> inflammatory responses
    – -> Further pancreatic parenchymal injury
    – The cytokines and chemokines generated from the pancreas can also multi-
    organ injury
29
Q

Acute Pancreatitis – Treatment

A
  • Supportive care
    – Nutritional support – aggressive fluid and electrolyte replacement
    – No oral administration of food for 48 hrs
  • Monitoring vital signs, urine output, O2 saturation
  • Anti-emetics
  • Analgesia – control of pain by NSAIDS, narcotics
  • Surgical treatment
  • Control of diarrhea – enzyme therapy (coated)
  • Antibiotics – for infected necrosis (not useful for acute)
  • Prevent future episodes – avoidance of alcohol