1 / 32

Haematology

Haematology. Group A. 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. Mr X cont…. On Examination:

victoria
Download Presentation

Haematology

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Haematology Group A

  2. 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).

  4. Mr X’s Biochemistry - FBC • Initial biochemistry: • Blood flim: • Marked anisocytosis (oval macrocytes +++) • Poikilocytes (tear drop & fragmented cells ++) • Red cells normochromatic • Neutropenia with marked neutrophil hypersegmentation • Thrombocytopenia.

  5. Mr X’s Biochemistry - LFTs

  6. 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

  7. Symptoms of Portal Hypertension • Common portal hypertensive complications include: • Hepatic encephalopathy • Bleeding esophageal varices • Ascites & spontaneous bacterial peritonitis • Hepatorenal syndrome

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. Bilirubin & Liver Disease • Generally, liver disease leads to mixed hyperbilirubinemia, i.e., high levels of both circulating (unconjugated) and conjugated bilirubin. (Total=84, 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

  15. 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

  16. 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

  17. Increased Levels Indicate: • MI • Stroke • Anaemia • Hypotension • Liver disease • Megaloblastic anaemia • Perniciour anaemia

  18. When is LD testing Performed • Possible diagnosis: • Anaemia of Vitamin B12 deficiency • Megaloblastic anaemia • Perniciour anaemia • LD isoenzyme levels may be requested

  19. 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

  20. What this tells us: • Tissue damage • Possible liver disease • Possible anaemia • Muscle injury • MI

  21. 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 > 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

  22. Parameter Value Reference Range Haptoglobin 0.3g/L 0.3-2.0g/L 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)

  23. 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 body’s iron stores

  24. 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

  25. Parameter Value Reference Range Ferritin 442μg/L (H) 33-330μg/L 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

  26. 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

  27. Folate–Deficient 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

  28. Megaloblastic Anemia • Results from defective DNA synthesis. RNA synthesis continues  increased cytoplasmic mass & maturation • I.e., All cells have dyspoiesis: cytoplasmic maturity > 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

  29. Parameter Value Reference Range 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 Mr X – are his results consistent with megaloblastic anaemia? • The patient’s 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.

  30. Mr X’s Biochemistry - FBC • Initial biochemistry: • Blood flim: • Marked anisocytosis (oval macrocytes +++) • Poikilocytes (tear drop & fragmented cells ++) • Red cells normochromatic • Neutropenia with marked neutrophil hypersegmentation • Thrombocytopenia.

  31. Mr X – are his results consistent with megaloblastic anaemia? • Mr X’s 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

  32. 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.

More Related