Haematology

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Haematology

• Group A

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Patient X

• A 61 year old male
• Presents with
• generalised weakness increasing dyspnoea on
  exertion for 3/52.
• Medical History
• Alcoholism
• Social History
• Divorced for 2 years
• Lives Alone
• Retrenched 6 years ago has not worked since

3
Mr X cont

• On Examination
• Pallor and scleral icterus were noted
• Clinical evidence of chronic alcoholic liver
  disease with portal hypertension
• Spleen was palpable (2cm).

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Mr Xs Biochemistry - FBC

• Initial biochemistry

PARAMETER VALUE REFERENCE RANGE
Hb 33 g/L (L) 130-180
MCV 125 fL (H) 80-100
WCC 2.4 x109/L (L) 4.0-11.0 x109/L
Neutrophils 30 (L) 0.72 x109/L 2.0-7.5 x109/L
Monocytes 5 (L) 0.12 x109/L 0.2-0.8 x109/L
Lymphocytes 65 1.56 x109/L 1.5-4.0 x109/L
Platelets 49 x109/L (L) 150-400 x109/L

• Blood flim
• Marked anisocytosis (oval macrocytes )
• Poikilocytes (tear drop fragmented cells )
• Red cells normochromatic
• Neutropenia with marked neutrophil
  hypersegmentation
• Thrombocytopenia.

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Mr Xs Biochemistry - LFTs
PARAMETER VALUE REFERENCE RANGE
Serum bilirubin (total) 84 µmol/L (H) 2-20
Conjugated bilirubin 44 µmol/L (H) 1-4
AST 420 U/L (H) 10-45
GGT 640 U/L (H) 0-50
LD 3162 U/L (H) 110-230
Haptoglobins 0.3 g/L 0.3-2.0
Ferritin 442 µg/L (H) 33-330
Serum B12 138 pmol/L 120-680
Serum folate 0.7 nmol/L (L) 7-45
Red cell folate 125 nmol/L (L) 360-1400
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Portal Hypertension

• Pressure in the hepatic portal vein is increased
• Most common cause is cirrhosis, but any liver
  disease can cause it
• In cirrhosis, hepatocytes regenerate more slowly
  than scar-tissue forms
• As the scar tissue shrinks, it obstructs blood
  flow through the hepatic portal system

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Symptoms of Portal Hypertension

• Common portal hypertensive complications include
• Hepatic encephalopathy
• Bleeding esophageal varices
• Ascites spontaneous bacterial peritonitis
• Hepatorenal syndrome

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Alcoholic Liver Disease

• A spectrum of clinical syndromes pathologic
  changes in the liver caused by alcohol. The
  spectrum includes fatty liver, alcoholic
  hepatitis alcoholic cirrohsis.
• Approximately 15 to 20 of those who abuse
  alcohol develop alcoholic hepatitis and/or
  cirrhosis, which may develop in succession or
  exist concomitantly
• The level of alcohol consumption necessary for
  the development of these advanced forms of
  alcoholic liver disease is probably 80 g of
  alcohol per day, the equivalent to 6 to 8 drinks
  daily for several years
• BUT, the threshold of alcohol necessary for the
  development of advanced alcoholic liver disease
  varies substantially among individuals

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Alcoholic Fatty Liver

• Also called steatosis
• Predominantly an asymptomatic condition that
  develops in response to a short duration (a few
  days) of alcohol abuse
• Up to 15 drinks a day for 10 days
• Entirely reversible with abstinence

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Alcoholic Hepatitis

• Prolonged alcohol abuse results in alcoholic
  hepatitis.
• Patients with this condition have various
  constitutional symptoms, such as fatigue,
  anorexia, weight loss, nausea and vomiting.
• Severe alcoholic hepatitis may be evident by
  advanced symptoms due to portal hypertension,
  including gastrointestinal (GI) bleeding,
  ascites, and hepatic encephalopathy.
• Other findings depend on the severity of liver
  insult and may include jaundice, splenomegaly,
  hepatic bruits, collateral vessels, and ascites.
• Reversible if patients stop drinking

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Alcoholic Cirrhosis

• Alcoholic cirrhosis may occur before, concomitant
  with, after, or independent of a bout of
  alcoholic hepatitis
• Characterized anatomically by widespread nodules
  in the liver combined with fibrosis
• Most common of specific organ damage in
  alcoholics
• The clinical history is similar to that of
  alcoholic hepatitis, symptoms are similar to
  those observed with other forms of end-stage
  liver disease

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Bilirubin

• Bilirubin A break-down product of haemoglobin
• Dying RBCs are engulfed destroyed by
  macrophages
• Heme is split from globin the iron core is
  salvaged
• The remaining heme molecule is degraded to
  bilirubin

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Bilirubin

• Unconjugated bilirubin is transported in the
  plasma bound to albumin
• This free bilirubin is conjugated with glucuronic
  acid in the liver.
• The conjugated bilirubin is then secreted in the
  bile as an orange-yellow pigment

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Bilirubin Liver Disease

• Generally, liver disease leads to mixed
  hyperbilirubinemia, i.e., high levels of both
  circulating (unconjugated) and conjugated
  bilirubin. (Total84, range 2-20) and conjugated
  44 micro mol/L, range 1-4
• This is due to impaired liver uptake of
  unconjugated, and impaired excretion of
  conjugated bilirubin from bile duct perhaps due
  to gallstones, hepatitis, trauma or long term
  alcohol abuse
• Also, an increase in bilirubin may mean too many
  RBC are getting destroyed

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Mr X are his bilirubin results consistent with
alcoholic liver disease?

• Hyperbilirubinemia excess of bilirubin in the
  blood
• Visible jaundice occurs at 20-30µmol/L
• The patient has jaundice (scleral icterus)
• History of alcoholism
• Mr X has mixed hyperbilirubinemia

PARAMETER VALUE REFERENCE RANGE
Serum bilirubin (total) 84 µmol/L (H) 2-20
Conjugated bilirubin 44 µmol/L (H) 1-4
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Lactate Dehydrogenase (LD)

• Cytoplasmic enzyme
• Its function is to catalyze the oxidation of
  L-lactate to pyruvate
• Assayed as a measure of anaerobic carbohydrate
  metabolism
• Present in heart, liver, kindey, lungs, skeletal
  muscle and brains
• Used as a diagnostic marker for MI, muscular
  disorders, malignancy and liver disease
• Not a specific marker

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Increased Levels Indicate

• MI
• Stroke
• Anaemia
• Hypotension
• Liver disease
• Megaloblastic anaemia
• Perniciour anaemia

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When is LD testing Performed

• Possible diagnosis
• Anaemia of Vitamin B12 deficiency
• Megaloblastic anaemia
• Perniciour anaemia
• LD isoenzyme levels may be requested

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Lactate Dehydrogenase Liver Disease

• LD has several isoenzymes (LD-1 to LD-5)
• LD-1 and 2
• MI, Renal infarction, megaloblastic anaemia
• LD-2 and 3
• Acute leukaemia
• LD-5
• Liver and skeletal muscle damage

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What this tells us

• Tissue damage
• Possible liver disease
• Possible anaemia
• Muscle injury
• MI

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Haptoglobins

• Plasma proteins that carry free haemoglobin
  (i.e., Hb NOT in RBCs)
• Blood levels used to detect haemolysis
  (intravascular destruction of RBC)
• Normally 10 of haemolysis is handled by
  haptoglobins and haemopexin
• Haemolysis gt Haptoglobin synthesis ? decrease in
  serum haptoglobin
• Lower than normal levels may indicate chronic
  liver disease, haemolytic anaemia, primary liver
  disease, AMI and some cancers
• Increased levels in certain chronic diseases and
  inflammatory disorders

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Mr X are his haptoglobin results consistent
with alcoholic liver disease?

• 0.3g/L is boarder-line low for the normal range
  (0.3 2.0g/L)

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Ferritin

• An iron compound synthesised in response to
  erythrophagocytosis
• Ferritin is stored in the liver, spleen bone
  marrow for eventual encorporation into
  haemoglobin
• Ferritin iron is the principle form of iron
  storage therefore serum ferritin levels indicate
  the bodys iron stores

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Ferritin

• Two main functions
• sequester potentially toxic iron into the
  apoferritin protein shell
• provide a readily accessible store of iron
• Can be used to diagnose iron deficiency anaemia
• In combination with serum iron and total
  iron-binding capacity tests, it can differentiate
  and classify different types of anaemia's

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Mr X are his ferritin results consistent with
alcoholic liver disease?

• 442µg/L is significantly higher than the upper
  normal range (33-330µg/L)
• This suggests a high level of erythrophagocytosis,
  most likely due to severe inflammatory liver
  disease

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Folate (Vitamin B9)

• Obtained from green, leafy vegetables
• Total body folate is 70mg
• 1/3 of this is stored in the liver
• In folate deficiency anaemia, the red cells are
  abnormally large (megalocytes)
• Precursors, in the bone marrow are megaloblasts
• Thus, this anaemia is referred to as
  megaloblastic anemia

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FolateDeficient Anaemia

• Causes of the anaemia are poor dietary intake of
  folic acid as in chronic alcoholism
• Causes of folic acid depletion include
• Poor intake (e.g., chronic alcoholism, diet
  lacking in fresh vegetables)
• Inadequate absorption/malabsorption syndrome
  (e.g, drug-induced by phenytoin, primidone,
  barbiturates celiac disease)
• Inadequate utilisation via antagonists such as
  methotrexate and trimethoprim
• Alcohol also interferes with its intestinal
  absorption, intermediate metabolism
  entero-hepatic salvage

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Megaloblastic Anemia

• Results from defective DNA synthesis. RNA
  synthesis continues ? increased cytoplasmic mass
  maturation
• I.e., All cells have dyspoiesis cytoplasmic
  maturity gt nuclear maturity ? production of
  megaloblasts
• Dyspoiesis ? increased intramedullary cell death
  ? hyperbilirubinemia hyperuricemia
• All cell lines are affected, so leukopenia
  thrombocytopenia may occur
• Main causes defective utilisation of folic acid
  or vitamin B12 deficiency cytotoxic drugs
  Di-Guliemo Syndrome

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Mr X are his results consistent with
megaloblastic anaemia?

• The patients Hb is low, indicating anaemia,
  while his elevated MCV indicates macrocytic
  anaemia.
• The patient has a serum folate of 0.7nmol/L, a
  RBC folate level of 125nmol/L which are well
  below the normal ranges. His serum B12 is within
  the normal range
• Normal serum B12 assay with a low RBC folate
  level are consistent with alcoholism
• Both of these results
• also support the diagnosis of
• megaloblastic anaemia due
• to folic acid deficiency.

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Mr Xs Biochemistry - FBC

• Initial biochemistry

PARAMETER VALUE REFERENCE RANGE
Hb 33 g/L (L) 130-180
MCV 125 fL (H) 80-100
WCC 2.4 x109/L (L) 4.0-11.0 x109/L
Neutrophils 30 (L) 0.72 x109/L 2.0-7.5 x109/L
Monocytes 5 (L) 0.12 x109/L 0.2-0.8 x109/L
Lymphocytes 65 1.56 x109/L 1.5-4.0 x109/L
Platelets 49 x109/L (L) 150-400 x109/L

• Blood flim
• Marked anisocytosis (oval macrocytes )
• Poikilocytes (tear drop fragmented cells )
• Red cells normochromatic
• Neutropenia with marked neutrophil
  hypersegmentation
• Thrombocytopenia.

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Mr X are his results consistent with
megaloblastic anaemia?

• Mr Xs neutrophils are below the normal range.
• This tends to occur in chronic disease states and
  megaloblastic anaemias
• Hypersegmentation of neutrophils occurs in 91 of
  cases megaloblastic anaemia

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Conclusions

• Mr X is experiencing multiple biochemical changes
  due to his chronic alcohol intake.
• Treatment for him is primarily supportive. He
  needs to improve his diet, and ideally, should
  cease alcohol intake.
• Corticosteroids may be indicated.