Macrocytic anemia

(common causes)

megaloblastic anemia (vitamin B12 or folate deficiencies)

liver disease

alchohol, hypothyroidism, reticulocytosis

Microcytic anemia

(common causes)

iron deficiency (blood loss, malabsorption, dietary deficiency, increased requirement)

thalassemia

sideroblastic

anemia of chronic disease

normocytic anemia

(common causes)

decreased production (aplastic anemia, renal disease)

increased destruction

hemorrhage

hemoglobinopathy (sickle cell anemia)

enzymopathy (G6PD deficiency, pyruvatic kinase deficiency)

membranopathy (hereditary spherocytosis)

immune- autoimmune hemolytic anemia

non-immune- DIC, hypersplenism

6 laboratory tests for microcytic anemia

Fe levels

total binding capacity

ferritin

review peripheral blood smear

hemoglobin electroporesis

bone marrow biopsy

laboratoy findings for iron deficiency anemia

(Hgb, sFe, TIBC, sFerritin, MCV, RDW, reticulocyte, bone marrow)

low blood hemoglobin concentration

low serum iron

high TIBC

low serum ferritin

low MCV

high RDW

low reticulocyte count

in bone marrow:  Prussian blue stain for iron is absent

1. impaired source: renal failure

2. reduced stimulation: endocrine disorders, hypothyroidism and testosterone deficiency

3. inflammatory cytokines, anemia of chronic disease

hypoplasia:  aplastic anemia, pure red cell aplasia

infiltration:  multiple myeloma, leukemia, fibrosis, metastatic malignancies

myelodysplastic disorders

elevated LDH

elevated indirect bilirubin

elevated reticulocyte count

decreased haptoglobin

MCV increased or normal

hereditary spherocytosis

elliptocytosis

acanthocytosis

paroxysmal nocturnal hemoglobinuria

polycythemia rubra vera

(definition, lab result, CP, population, cause)

clonal disorder of the pluripotent hematopoietic stem cell

increased red cell mass

leukocytosis and thrombocytosis

splenomegaly

males>females

avg. age is >60

JAK2 gene mutation

vascular thromboses (venous and arterial)

bleeding

leg ulcres

splenic infarcts

myeloid metaplasia

acute leukemia

36y/o obese female presents with RUQ pain x 4hr, after a fatty meal, radiating to the R scapula, associated with nausea. Pt is pain-free now. No prior episodes. On physical exam, minimal RUQ tenderness was observed, no Murphy’s sign elicited. RUQ U/S reveals (marked in arrow) without GB wall thickening (<3mm) or pericholecystic fluid. Diagnosis: ?

36y/o Asian female presents with RUQ pain x 4hr, after a fatty meal, radiating to the R scapula, associated with nausea. Pt is pain-free now. No prior episodes. On physical exam, minimal RUQ tenderness was observed, no Murphy’s sign elicited. Patient is a known case of sickle cell anemia. RUQ U/S reveals (marked in arrow) without GB wall thickening or pericholecystic fluid. Indirect bilirubin is elevated. Ultrasound shows beaded appearance. Diagnosis: ?

46yo F w RUQ pain > 24hrs of RUQ pain radiating to the R scapula, started after fatty meal, a/w nausea, vomiting, fever. Exam: Palpable, tender gallbladder, guarding, +Murphy’s = inspiratory arrest. No similar episodes in past.U/S: solitary gallstone, wall thickening (>4mm), GB distension, pericholecystic fluid, sonographic Murphy’s sign present. Lab results point to infection.

87yo M critically ill, on long-term TPN w RUQ pain. Abdomen is tender. Murphy’s sign elicited. No similar episodes in past. Ultrasound: No GB wall thickening, pericholecystic fluid present, no gallstones. Diagnosis: ?

76y/o female presents with RUQ pain x 24hr, after a fatty meal, radiating to the R scapula.. Several previous episodes are noted over last several years. Management was always conservative. Minimal RUQ tenderness noted, no Murphy’s. Ultrasound: GB wall 6mm, no pericholecystic fluid, no gallstones. Diagnosis: ?

46yo F p/w RUQ pain, jaundice, acholic stools, dark tea-colored urine, no fever. Past history of cholelithiasis. No treatment ever undertaken. Exam: unremarkable. HepB/C neg. Ultrasound: solitary CBD stone, dilated CBD > 1cm. Diagnosis: ?

46yo F p/w acute RUQ pain, jaundice, acholic stools, dark tea-colored urine. Her blood cultures came back positive for a facultative anaerobic bug. Gram staining is shown. Two weeks ago, she had a biliary colic like pain. U/S at that time revealed multiple small stone in the common bile duct. She decided against any management at that time.

High temperature, increased direct bilirubin, decreased urobilinogen, high leukocytes

72 yo F p/w mild RUQ pain since last several months. She also complains of intermittent episodes of acute colicky pain. She gives past history of gall stones. Her last U/S taken 2 years ago reveal thickend gall bladder, with multiple stones. No pericystic fluid was observed. CBD was not affected.  Her present U/S reveals an infiltrative mass occupying most of the gall bladder. Also noticed are gall stones. Cholecystectomy was performed. Gross and histo-pathology are shown. Diagnosis?

signet ring cells are present, increased extracellular mucin release

increased desmoplasia causes gastric wall to become rigid, giving patient the 'leather bottle' feeling

cholesterol, brown stones- radioluscent

calcium carbonate, black stones- radiopaque

Menckel's diverticulum

(location and complications)

antimesenteric side of the ileum

ulceration, obstrutction, perforation, intussusception, and neoplasms

hematemesis/ melena, obstruction, pain, nausea, vomiting

chronic gastritis is from H.pylori infection or autoimmunity

Peptic Ulcer Disease

(E, G, CF)

predisposing factors (H. pylori, NSAIDs, psychologic stress, caffeine, alcohol, and tobacco, radiation injury, chronic bile reflux, mechanical injury, systemic diseases such as Crohn's disease, amyloidosis, graft-versus-host, Zollinger Ellison syndrome)

smooth, oval, punched out single ulcer

pain occurs 1-3 hours after meals, worse at night

Zollinger Ellison syndrome

(D, G, M)

gastinomas found in small intestine and pancreas

multiple ulcers in stomach

doubling of oxyntic cells, mucosal thickness

pallor of skin

pallor of conjunctivae

koilonychia (changes in nails) w/ Fe def.

skeletal chagnes in hemoglobinopathies

acanthocytes

(description, mechanism, disorders)

small spherical cells with irregular thornlike projections

membranes with altered lipid content

associated with abetalipoproteinuria, liver disease, etx.

target cells

(description, disorders)

increased surface to volume ratio

associated with liver disease, thalassemia, iron def., Hgb S, Hgb C

tear drop

(disorders)

echinocytes AKA burr cells

basophilic stippling

(composition, disorders)

aggregated ribosomes

associated with thalassemia, Pb poisoning

Howell-Jolly bodies

(appearance, composition, disorder)

dark blue spherical granules in RBCs

nuclear DNA fragments

splenectomy

internal- recycled

external- lost

when RBCs lyse and haptoglobin is depeleted free Hgb is oxidized to methemoglobin

if reabsorbed it is catabolized by renal tubular cells

EPO, secondary erythrocytosis = increased EPO

polycythemia vera does not

dysphagia, glossitis, iron def. anemia

endoscopy performed

splenomegaly, episodic hemolysis when exposed to something that generates oxidant stress

asymptomatic unless triggered

treatment:  transfusions, avoidance

a point mutation on beta globin

lysine substitutes glutamate

a reduction of intracellular pH results in a decreased oxygen affinity for hemoglobin

prolonged transit time in the microvasculature, can result in irrreversible sickling

gall stones

vascular occlusion

aplastic crisis (B19)

ischemic necrosis due to salmonella or staph infection

ulceration on distal leg

painful crises are treated with fluid, oxygen supplementation, and analgesics

blood transfusions used for manifestations of chest syndrome, stroke, and priapism

hydroxyurea increased HbF and decreases chance of vas-occlusion

Hemoglobin C disease

(CF, LF)

homozygous- same as HbS

target cells and rectangular RBCs

- splicing mutations (beta +)

- promoter region mutations (beta +)

- chain terminator mutations (beta 0)

unpaired alpha chains form insoluble inclusions. red cell precursors suffer from membrane damage--> apoptosis

ineffecitve erythropoeisis results in cachexia and excessive iron absorption

bone marrow hyperplasia leading to skeletal deformity

if untreated--> growth retardation

skeletal abnormalities

deletion of 3 a-globin chains

asian

deletion of 4 alpha-globin chains

hemoglobin Barts

pallor, edema, massive hepatosplenomegaly

fetuses die soon

PNH

(D, P)

acquired clonal stem cell disorder

mutations in PIGA(x-linked) or lyonization (inactivation)--> lack of synthesis of GPI-anchor proteins, all blood cells can be affected

GPI-anchored, complement-regulating proteins CD55 (inhibites C3 convertase), CD59 binds C8-->cell lysis vulnerability--> acidosis during sleep

PNH

(CF, LF, T)

hemosiderinuria--> iron def.

thrombosis (platelet inhibitor attached to GPI)

can lead to AML

flow cytometry of GPI-linked proteins

only cure is bone marrow transplantation

RBCs in sera containing antibodies or complement

if antigen present agglutination occurs

patient serum mixed with red cells that have known antigens

if antibodies present agglutination will occur

extravascular hemolysis

IgG coated red blood cells bind Fc receptors on phagocytes, biting, Rh is often targeted

DAT is positive

unconjugated bilirubin

treatment:  steroids, immunosuppressive therapy

IgM antiobodies bind at "cold" temperature

from infections or B cell neoplasms

exposed body parts may experience pallor, cyanosis, and Raynaud phenomenom due to occlusion of vasculature by agglutinated red blood cells

exacerbated in winter

DAT positive for complement

IgG autoantibodies bind the P blood group antigen in cooler regions of the body

severe intravascular hemolysis

 microvascualr lesions narrow the vessel lumen usually due to platelet or fibrin deposition

causes:  DIC, TTP, HUS, malignant hypertension

neuro, glossitis

erythroid hyperplasia, ineffective erythropoiesis

elevated methylmalonic acid

Schilling test- radioactive B12 if less than 7.5% is excreted than PA is suspected

iron balance is regulated by absorption in the duodenum

no excretory regulation, removed by cell sloughing

non-hemem iron need DMT1 to cross apical membrane

serum iorn- transferrin-bound iron

TIBC- iorn that can be bound to transferrin in serum

transferrin saturation

ferritin- amount of iron stored

lower serum iron and transferrin saturation levels w/o causing anemia

storage iron, hemoglobin, transport iron, enzyme iron

CF of iron deficiency anemia

fatigability, tachycardia, palpitations and tachypnea upon min. exertion

pallor

pica

plummer-vinson syndrome (eesophageal webs, microcytic hypochromic anemia, glossitis

chronic (koilonychia, alopecia, malabsorption)

symptoms are that of underlying disorder

increased iron in marrow macrophages

elevated serum ferritin level (decreased iron incorporation and it is an acute phase reactant)

decreased TIBC

AR, defect DNA repair complex, associated with hypolplasia of kidney and spleen, bone anomalies

aplastic anemia can also be a result of telomerase defects

Viral Enterocolitis

(Morphology)

shorter intestinal villi

lymphoid lamina propia inflammation

Crohn's disease

(CF, RF)

RLQ, diarrhea

aphtous ulcers, pyoderma gangrenosum, uveitis, erythema nodosum, sclerosing cholangitis, arthritis, clubbing

Ashkenazi Jews, family history

assymetric distribution, cobblestone mucosa, fistulation

gluten sensitive eneteropathy

whipple's disease

eosinophilic gastroenteritis

pancreatic insufficiency

intraluminal bile salt deficiencies

parasitic infestation

drug induced

Celiac Sprue

(D, RF,

increased cytoplasmic volume

scalloping RBC

basophilia on edge touching RBC

darker nuclei

CD10 and CD19 positive

Tdt and CD22

cholesterol

Crohn's disease

AML-adults

ALL- children

80-90%

segmental, whereas UC is diffuse

ASCA

saccharomyces cerevisiae antibody

sclerosing cholangitis

and adenocarcinoma

mutated APC--> defective mismatch repair-->genomic instability

hundreds of colonic polyps by 20s

linitis plastica or shrunken stomach

from autoimmunity against parietal cells

can lead to adenocarcinoma

inflammation into lobules form portal triads

ballooning degeneration of hepatocytes

primary biliary cirrhosis

population and pathology

upper abdominal pain

extensive peritoneal fluid collection in dilated loops of small bowel

PAS-positive macrophages

extraintestinal defects- polyarthritis, hallucinations

Chronic Nonspecific Lymphadenitis

cause

results from chronic immunological stimuli

(viral, protozoal, antibodies, etc.)

Follicular Hyperplasia

M, Causes

large germinal centers surrounded by a collar of small resting naive B cells

rheumatoid arthritis

Chronic Lymphocytic Leukemia

(markers, population)

CD5, 19, 23, smudge cells

Old males

middle age lymphoma composed of cleaved and noncleaved b cells in a nodular pattern, seen in BM

14:18 translocation, antibody to BCL2 locus

overexpression of BCL2

Burkitt Lymphoma

M, cancer bio, associated virus

B cells with basophilic cytoplasm and numerous mitotic figures, Starry Night (Van Gogh) pattern

(8:14) c-MYC translocations are always present- does not express BLC2

EBV virus

Mantle Cell Lymphoma

cancer bio, population, involvement, prognosis

(11:14)(13;32) and cyclin D1 overexpression

50-60 male

blood, BM, spleen

poor

Define Plasma Cell Neoplasms:

multiple myeloma

plasmacytoma

smoldering myeloma

Waldenstreom macroglobulinemia

monoclonal gammopathy of undetermined significance

MM: neoplastic masses scattered throughout the P: skeletal system

SM: single mass in bone or soft tissue

WM: high plasma M component without symptoms

MGUS:  M compmonents in blood

Multiple Myeloma

(populaiton, CF, LF, prognosis)

male, Africans, late 60s

bone pain, constipation, recurrent infections, Bence Jones proteinuria (light chains), punched out lytic bone lesions

binucleated, plasmablases, mott cells, CD138 marker

median survival is 4 to 6 years

Hodgkin's lymphoma

D, E, LF, spread

heterogenous cellularity

arises from single node or chain of nodes

Reed-Sternberg cells CD15, 30

nodal, splenic, hepatic, marrow and others

Adult T cell Luekemia

associated virus, CF, LF, prognonsis

endemic HTLV-1

skin lesions, lymphoid tissue enlargement, hypercalcemia

clover leaf cells

less than 1 year

Mycosis Fungoides

Defintion, prognosis, CF

tumor of skin CD4 helper cells

median survival 8-9

cutaneous lesions inflammation--> plaque --> tumor

Anaplastic Large-Cell Lymphoma

definition, cancer bio, population, prognosis

cells with abundant cytoplasm and horshoe nuclei

rearrangement in the ALK gene on chromosome 2p23

children

very good prognosis

Crigler-Najjar syndrome

D, CF, LF, T

rare, AR, results in absent or decreased levels of UDPGT

Type I- jaundice appears early, Type II- jaundice appears later

plasma exchange transfusion, phototherapy

Gilbert's Syndrome

D, E

common, AD, unconjugated bilirubin buildup

gene coding region is normal, but transcriptor is mutated

Dubin-Johnson syndrome

D, E, M, D

increases in conjugated bilirubin without elevations of liver enzymes due to defective calanicular transport of conjugated bilirubin from hepatocytes

common in Iranian Jews, AR

pigment deposition in lysosomes causes the liver to turn black

elevated GGT. increased urinary coprpporphyrin

Rotor Syndrome

D

Primary Biliary Cirrhosis

D, P, C, T

chronic, autoimmune cholestatic liver disease, destruction of intrahepatic bile ducts

elevated IgM, Anti-mitochondrial antibodies

eyelid xanthelasmas, skin hyperpigmentationm, arthropathy, cirrhosis

MTX,

Primary Sclerosing Cholangitis

D, M, LF

chronic cholestatic disorder characterized by inflammation, fibrosis, and strictures of intra and extrahepatic bile ducts with dilated of preserved segments, associated with UC

onion skin fibrosis, beading of biliary tree on radiographs

pANCA, SMA

Cystic Fibrosis

D, P,

AR mutation in genes that control chloride anion transport into mucosal epithelium, this results in impaired Na+ transport, thick mucus

salty sweat

Wilson's Disease

P, T

impaired ATP7B gene which transports copper from hepatocytes to bile

penicillinamine binds copper leading to excretion

hemochromatosis

D, LF, T

mutation in HFE which regulates iron absorption

increased AST and ALT, irondeposition on Prussian stain

frequent phlebotomy

Reye's syndrome

P, M

damage to mitochondria

brain edema, fatty liver

Cholangiocarcinoma

P