pathology

Presentation 30 to 40 year old patient has episodes of visceral autonomic dysfunction (typically results in abdominal pain ), sensorimotor neuropathy ( tingling, weakness ), and psychiatric symptoms . Episodes can last anywhere from a few days to weeks. For example 40 year old with acute onset of psychosis (delusions, insomnia, irritability), abdominal pain, and peripheral neuropathy (tingling in hands/ feet). There is usually a family history of mental illness e.g. schizophrenia. On physical exam, the abdomen is soft and usually non-tender or only minimally tender, this is because the abdominal pain is neuropathic. Patients may also have constipation, vomiting, anxiety, and mood changes. The onset is usually when patients are in their 30s and 40s . Pathology Partial deficiency of prophobilinogen deaminase , which is required for heme synthesis. Diagnosis  Elevated urinary porphobilinogen (dark red/ brown urine) Management Glucose in high doses can inhibit heme...

Patient will have a ruddy face (facial plethora), high blood pressure, and itching that occurs after exposure to water e.g. after bath/ shower (aquagenic pruritis). Physical exam will show splenomegaly. Some patients may present with burning in hands/ feet (erythromelalgia), transient visual disturbances, bleeding, and gouty arthritis (increased RBC turnover). CBC will show very high hemoglobin and hematocrit, high platelet count and WBC count. Increased blood viscosity is responsible for the visual disturbances, the hypertension, etc. It is important to know the mutation responsible for PV - a JAK2 mutation that results in the gene always being active. The gene produces a JAK2 tyrosine kinase that differentiates myeloid cells into erythrocytes (red blood cells). Normally, the gene is activated by erythropoietin (EPO) released by the kidneys (less so the liver) when there is tissue hypoxia. With the always active gene, erythropoietin isn't needed and the levels are low. This i...

Patient will have a severe infection that may require longer than normal to improve even with antibiotics. On CBC, the WBC count will be markedly elevated (typically >50,000). On peripheral smear, there will be many immature forms of neutrophils (myelocytes, promyelocytes, metamyelocytes, bands). However, most will be further along in maturation (i.e. more bands). Look for a high leukocyte alkaline phosphatase (LAP) score. Differential Dx The LAP score helps differentiate this from CML which can also present with infections as well as immature forms of neutrophils (myelocytes, metamyelocytes) but has a low LAP score. This is because the neutrophil precursors are so immature that they don't function as well. CML also usually has a higher WBC count (typically >100,000). Also unlike CML, leukemoid reaction does not present with increased basophils. Relevant Images More of the mature neutrophil precursors e.g. bands, metamyleocytes as well as mature (segmented) neutrophil...

Quick Review Patient is often older, and can no symptoms or have B symptoms (night sweats, etc), fatigue, and weight loss (caused by early satiety due to enlarged spleen). On physical exam, an enlarged spleen can be palpated. CBC shows very high WBC count (typically >100,000) with elevated basophils on differential. Peripheral smear shows early, immature neutrophil precursors (myelocytes, metamyelocytes) as well as many basophils. It is important for CML to know the details of the genetic abnormality because it relates to the treatment. CML is due to a translocation of BCR and ABL on chromosomes 9 and 22 resulting a fusion BCR-ABL gene that produces a tyrosine kinase that is always active. The treatment of choice is a tyrosine kinase inhibitor e.g. imatinib. They work to suppress the tyrosine kinase and can induce disease remission. Relevant Images Immature neutrophil precursors on peripheral smear BCR-ABL translocation

Quick Review Patient is an adult (usually older, but can also be younger) with fatigue (due to anemia) and bleeding (due to thrombocytopenia) and on CBC there is decreased hemoglobin, decreased platelets, and WBC varies (can be normal, increased or decreased).  LDH will be elevated. The most important form of AML to know is acute promyelocytic leukemia (APML). On peripheral smear, AML presents with myeloblasts with Auer rods. Bone marrow biopsy will show myeloid blasts, for APML this would be atypical promyelocytes. In AML, the bone marrow is crowded with immature myeloid cells ("blasts") preventing development of other cell types (platelets, RBCs, normal WBCs). These myeloblasts are also present in the peripheral blood in large numbers. This is why patients have fatigue (anemia), bleeding/ bruising (thrombocytopenia), increased infections (granulocytopenia). APML can present with DIC (disseminated intravascular coagulation) which results in elevated PT and aPTT and re...

Quick Review Patient will be elderly (>65 y.o), have fatigue (due to anemia) and large firm mobile lymph nodes (supraclavicular, axillary and/or cervical lymph nodes). Splenomegaly on abdominal exam. Some patients may have B symptoms (night sweats, fever, etc). Some may have increased infections or weight loss. Some may be asymptomatic. The key features are elderly patient with abnormal CBC and peripheral smear. CBC will show elevated WBC count, and on differential elevated lymphocytes. Peripheral smear will show increased lymphocytes (lymphocytosis) and they will be mature (small, little cytoplasm); smudge cells may also be seen. Flow cytometry confirms presence of clonal expansion of B lymphocytes by finding CD20, CD19, CD5 etc. Biopsy of the lymph nodes and bone marrow is not usually needed. Key Features most common leukemia in the USA elderly "mature" patients lymphocytosis (elevated WBC count due to lymphocytes, increased lymphocytes on smear) lymphocyte...

Quick Review Child develops bloody diarrhea (sometimes it's not bloody) and abdominal pain and is given antibiotics which help with the diarrhea. Then about a week later is overly tired with pale skin and petechiae. They also often have reduced urine output (oliguria) and swelling (edema). CBC shows low hemoglobin (anemia), normal MCV (normocytic), low platelets (thrombocytopenia). Serum chemistry shows elevated BUN and Cr (renal damage). Liver function testing shows elevated bilirubin (suggests hemolysis). Peripheral blood smear shows schistocytes. Diagnosis is based on history and above laboratory tests. Treatment is supportive (fluids, electrolytes, blood transfusions, dialysis). The cause is Shiga toxin producing bacteria, usually E. coli O157:H7 which is a strain of enterohemorrhagic E. coli (EHEC). The toxin destroys the epithelial lining of the colon leading to abdominal pain and bloody diarrhea. Once in the blood the toxin damages endothelium leading to platelet microth...

Quick Review A 2 year old boy is brought to the clinic because of a swollen painful knee after injury during play or a fall. On exam the knee is very swollen, there is limited range of motion, and there is ecchymoses and swelling around the areas of the leg that were injured (e.g. thigh, shin, hip). There may be a family history of a male relative dying of a deep brain bleed or a male relative with similar problems with joint swelling, easy bruising or delayed bleeding after dental procedure (e.g. tooth extraction). Only male family members are affected (x-linked recessive). Physical exam will show limited mobility and pain on movement. X-ray of the joint will show a large effusion (hemarthrosis). CBC will be normal. Coagulation studies will show elevated aPTT, and either reduced factor VIII (hemophilia A) or factor IX (hemophilia B) activity. Treatment is to replace the missing coagulation factor. Desmopressin may be given for mild hemophilia A. Years later the boy has injured t...