Pathology Flashcards
(66 cards)
What are the levels for anemia in men and women
Less than 13 mg/dL men
Less than 12 mg/dL women
Lower for menstration
What does cachectic mean
Mal-nourished
What do labs for RBC count give
What do RBC indices give?
- Hemoglobin
- Hematocrit
- Reticulocyte Count
- Mean cell volume
- Mean cell hemoglobin
- Mean cell hemoglobin concentration
- Red cell distribution width
What MCVs show Microcytic vs Macrocytic anemia’s
Less than 80um cubed is microcytic
More than 100 um cube is macrocytic
80-100 is Normocytic
What are the symptoms of anemia
Fatigue Low blood pressure Pale Chewing ice Dyspnea Palpitations Roaring sound in the ears
What are the symptoms of Polycythemia?
Possibly none
Hyperviscosity leading to thrombosis
Vertigo tinnitus Headache Visual disturbances Hepatosplenomegaly Easy bruising Ruddy complexion
What happens to RBC progenitors as they change to mature RBC?
The nuclear volume decreases, gradual decrease in polyribosomes with increase in hemoglobin. Mitochondria and other organelles gradually disappear.
Penultimate form is reticulocyte. These enter circulation with a few polyribosomes that can stain blue. They quickly lose them.
What is Hemolytic Anemia generally and what are the hallmark signs of hemolytic anemia?
Accelerated red cell destruction
Erythrocytes hyperplasia in bone marrow and reticulocytosis
What is extravascular hemolysis
When premature destruction of RBC occurs within phagocytes.
Can lead to splenomegaly because of reduced DEFORMABILITY to enter scenic sinusoids.
Symptoms: anemia, splenomegaly, jaundice
Might benefit from splenectomy.
What is intravascular hemolysis
Injury that is severe enough that RBC burst in circulation.
Can be caused by mechanical force, turbulence, or biochemical agents
Signs: Hemoglobinemia, hemoglobinuria, and hemsiderinuria (iron binding protein in kidney). Also decrease serum haptoglobin and loss of iron.
Hereditary Spherocytosis
Why does it lower oxygen capacity
Autosomal Dominant
Inherited defects in cytoskeleton (Spectrin to bind short actin filaments at other end of cell) that lead to formation of spherocytes. They are no deformable and they are vulnerable to sequestration and destruction in the spleen.
Mutations cause problems with spectrin, ankyrin, or band 3
Lose RBC and lose surface area-to-volume ratio
Splenectomy will stop the anemia, but the Spherocytosis will persist. Splenomegaly is common because of congested splenic cords.
They are dark red RBC with no central pallor on smears.
Will cause hyperplasia by RBC progenitors in marrow and increase reticulocytosis. Formation of gall stones (cholelithiasis) are common
Clinical FEATURES: anemia, splenomegaly, jaundice. Can have increased osmotic fragility. Parvovirus B19 will kill progenitors and worsen anemia
Glucose-6-Phosphate Dehydrogenase Deficiency
Problem with G6PD will lower NADPH in RBC and stop producing GSH to stop ROS.
X-linked recessive
Types: G6PD A: black males in US. Normal enzyme with shorter Half-life
Mediterranean: severe enzyme deficiency
Episodic hemolysis is caused by oxidant stress through drugs (anti malarial, sulfonamides, aspirin, nitrofurantoin) ***Fava beans, OR infection that cause H2O2 to be formed
Will form Heinz bodies (oxidized hemoglobin). Can cause intravascular hemolysis.
If they return to spleen you can get BITE CELLS where splenic phagocytes attempt to puck Heinz bodies. Usually are extravascular hemolyzed after in spleen.
Happens 2-3 days after drug exposure. Marrow will make more cells that will stop less severe cases even if drug use continues.
Paroxysmal Nocturnal Hemoglobinuria
Hemolytic Anemia from acquired mutation in PIGA
PIGA codes for synthesis of GPI (a membrane anchor for protein)
X-linked Acquired. Only have one active PIGA gene so you can have the gene and not express it if female.
Defieiciency is in hematopoietic stem cells so can happen in any clonal progeny, mostly RBC.
GPI proteins that regulate complement are affected: (CD55, CD59 and C8 binding protein)
Without CD59 complement MAC (C5b-C9) attacks cells in intravascular hemolysis. Complement is increased by decreased blood pH during sleep.
Present with anemia, Fe deficiency, and chronic intravascular hemolysis.
Thrombosis is leading cause of disease.
Diagnosed by flow cytometry to check for CD59 and CD55
Treatment: Eculizumab: C5 inhibitor. Can lead to meningococcal infections. Only cure is hematopoietic stem cell transplant
Immunohemolytic Anemia
2 kinds?
Caused by AB’s that bind to determinant on the RBC membranes.
Diagnosis depends on detection of AB and/or complement. Coombs test used and a positive test is agglutinate cells.
Warm: antibody immunohemolytic Anemia: Caused by IgG binding at 37 C. Cause chronic mild anemia and moderate splenomegaly. Make spherocytes
Cold: antibody immunohemolytic anemia. IgM fixes complement below 30 C in distal parts of body. Hemolysis is extravascular. Will cause Raynaud phenomenon
Hemolytic Anemia resulting form Mechanical Trauma to RBC
Mechanical Force trauma caused by defective cardiac valves, or more commonly by activity involving repeated physical pounding. (Marathon, bongos)
Micro angioplasty is hemolytic anemia is in small vessels that passing RBC can be damaged by clots or narrow vessels. MH
Mechanical fragmentation makes burr, helmet, or triangle cells in blood smears. (Sign)
Sickle Cell Anemia
Types of Crisis?
Single AA substitute. Glutamate swapped for Valine.
Familial hemolytic Anemia
In Sickle Cell HbA is replaced by HbS. In heterozygous carriers only 1/2 replaced
On deoxygenation cell becomes sickle shaped. With Oxygen they can be Biconcave. Ca comes in to cell and water/potassium leave. With time the cell damage become irreversible and the sickle cell undergo hemolysis rapidly by extravascular hemolysis.
Two consequences: Chronic moderately severe hemolytic anemia and vascular obstructions. Average life of RBC is 20 days
SC anemia causes microvascular ischemia and breakdown of heme to bilirubin. Ischemia can happen in any organ
Compensatory hyperplasia of erythroid progenitors in marrow. The marrow changes cause prominent cheekbones and “crew cut” skull. Even the spleen and liver may start hematopoiesis. Reticulocytosis will be seen too.
Children will have splenomegaly from extravascular hemolysis by adulthood you will have a fibrous autospleenectomy. Hemosiderosis and pigment gallstones are common.
Starts around 6 months of age and is punctuated by sudden crisis due to infarcted tissue.
Types of Crisis:
Vasoocclusive crises: Pain and tissue damage. Hand-foot Syndrome, acute chest syndrome, stroke, proliferation retinopathy
Aplastic crisis: Decrease of RBC triggered by infections (parvovirus B19). Very prone to infections like pneumococci and salmonella osteomyelitis.
Diagnosis by seen cells and electrophoretic demonstration of HbS
Treatment: Hydroxyurea (gentle inhibitor of DNA synthesis) allogeneic bone marrow transplant. Moderate treatment with penicillin to prevent pneumococcal infections.
Generally what is Thalessemia
Morphology of a and B
Quantitative problem.
Decrease synthesis of a or B globin.
Heterozygotes protect against malaria
A-globin problems from 2 genes on chromosome 16
B-globin is from 1 gene on chromosome 11
Morphology
In smears of B-minor and alpha RBC are microcytic and hypochromic but regular shape. May see dark-red puddles in cells
In B-major there are variations in shape and size. You also see normoblasts (nucleated RBC that aren’t mature).
Profound ineffective erythropoiesis with hyperplasia of erythoid progenitors. Expanded marrow and may invade bony cortex and may produce skeletal deformities
B-Thalassemia
2 kinds
B0, no B-globin produced
B+: reduced B-globin synthesis
Mostly single-base changes. Most lead to abnormal RNA splicing. Person with 1 of 2 have B-thalassemia minor (trait***) asymptomatic or mild
Both genes have mutation is B0 or B+ B-thalassemia major.
Occasionally one B+ gene can cause B-thalassemia intermedia.
Defect in B-globin causes anemia by
- Inadequate HbA formation in microcytic RBC
- And by allowing accumulation of unpaired a-globin chains that is a toxic precipitate. Few RBCs that live have short life span
Inappropriate hematopoiesis will increase dietary iron absorption. Increased iron will lower hepcidin which is a negative regulator of iron absorption
a-Thalassemia
A-thalassemia is caused by deletions by one up to four genes.
1 gene deletion is silent carrier
4 gene deletions is lethal in utero
3 deletions is excess of B-globin or y-globin. They form stable HbH and Hb Bart. These cause less damage than the free a-globin concentrates. HbH and Hb Bart have high affinity for oxygen so they are ineffective deliverers.
B-thalassemia major morphology
Splenomegaly, hepatomegaly, and lymphadenopathy. Ineffective erythropoietin precursors that consume lots of nutrients and produce growth retardation.
Must prevent iron overload of overabsorption. Severe hemosiderosis may develop
The hyperplasia is seen in HbH and intermedia as well **
Clinical features of thalassemia
B-minor and a are typically asymptomatic. Maybe mild microcytic hypochromic anemia.
Normal life expectancy.
Major presents as HbF diminishes. May suffer growth retardation. Patients sustained by blood transfusions which will reduce the skeletal deformities. There is still systemic iron overload from gut and now transfusion. You can live off transfusions for 2 or 3 decades.
Hematopoietic stem cell transplant at an early age is treatment of choice.
Again HbH and B-thalassemia intermedia aren’t as severe as major, and monitoring is required. Iron overload is rarely seen and transfusions aren’t required.
Diagnosis of major by Hb electrophoresis will show reduction of HbA and increased HbF
Diagnosis of minor made by Hb electrophoresis with slightly lower HbA and increased HbA2
In HbH you see H Hb subtypes because they form tetramers that are still stable without a-globin
Which protein can transfer iron in plasma?
Transferrin. Takes it to synthesize hemoglobin.
What is Ferritin
Protein-iron complex that is found within macrophages that breakdown RBC
What is hypochromic RBC?
RBC that are more pink. Less color
