Haemopoesis

Question 1

haemoposeis

where does it happen in adults / kids?

what are the stem cells?

Answer 1

formation of RBC

adults = bone marrow of axial skeleton ( pelvis, sternum, skull, ribs)

kids = liver and spleen

-haemopoietic stem cells

Question 2

how do you test for bone marrow functioning?

Answer 2

bone marrow biopsy of axial skeleton (usually pelvis)

put it in trephine biopsy

look at bone marrow and look at architecture of the bone marrow

Question 3

what do the main 5 lineage pathways arise from?

what are the 5 pathways?

and what differentiates it?

what are important ^?

Answer 3

haemopoietic stem cells

thrombopoiesis , granulopoiesis (basophils, neutrophils, eosinophils) ,monocytopoiesis, lymphopoiesis, erythropoiesis

hormones/ transcription factors/ interactions with non-haemopeotic cells types (endothelial cells)

erythropoietin secreted by kidney c ^ in RBC by decreasing the number of RBC that undergo apoptosis

Question 4

haemopoietic stem cells

Answer 4

capable of self renewal ( more so than other tissue types)

can differentiate to other cells depending on the stimuli

in patholgical conditions like tha

Question 5

sources of HPSCs

Answer 5

bone marrow aspiration (rarely done)

GCSF mobilised peripheral blood stem cells (collected by leucopharesis[lab technique seperated from blood sample])

umbilcal cord ‘ cord bank’

Question 6

reticuloendothelial system (RES) ?

blood & tissue?

main RES organs

types of macrophages depending on the tissue

Answer 6

-network of cells located throughout the body involved in the removal of dead or damaged cells and identify and destroy foreign antigens in blood and tissues

made of monocytes (in blood) and macrophages (in tissues)

types of macrophages depending on the tissue;

liver ; kupffer cells

tissue histiocyte ; CT

microglia ; CNS

peritoneal macrophage ; peritoneal cavity

red pulp macrophage ; spleen

langerhans cells ; skin and mucosa

Question 7

spleen location and functions and structure

Answer 7

located; inferior to the diaphram , posterior to the stomach ,

Functions = dispose RBC damaged and old , identify and destroy antigens in blood and tissues

white (similar structure to lymphoid follicles) and red pulp (sinuses lined by endothelial macrophages and cords)

Question 8

functions of the spleen in adults

Answer 8

• sequestration and phagocytosis; old/ abnormal RBC removed by macriphages
• blood pooling ; platelets and RBC can e rapidly mobilised during bleeding
• extramedullary haemopoiesis ; pluripotential stem cells proliferate during haematological stress or if marrow fails (e.g in muelofibrosis)
• immunological function ; 25% of T cellsand 15% of B cells present in spleen

Question 9

how does blood enter the spleen?

what are the pulps?

another function of spleen

Answer 9

• blood enters via splenic artery
• synthesises antibodies and removed antigen-coated bacteria white pulp
• Red bled cells pass through and are filtered in + the red pulp metabolises Hb also
• spleen can also serve as a blood pooling function where plateletes and RBC can be mobilised during bleeding?

Question 10

Splenomegaly causes

Answer 10

• high portal hypertension in liver disease
• over work (red or white pulp)
• reverting to what it used to do -extramedullary haemopoiesis due to high stress on the bone marrow (often seen on thalassemia)
• expanding as infiltrated by cells ( cancers cells orginiating the blood or metastases)
• expanding as infiltrated by other material liek waste in Gaucher’s disease, a defect in the beta-glucosidase enzyme catalses the breakdown of glucocerebroside, a consitiuent of RBC and WBC membrane and this accumulate in fibrils
• some infectious diseases like (sarcoidosis (granulomas like TB infections), HIV and glandular diseasecaused by Epstein Barr virus (EBV)

Question 11

how to examine spleen

Answer 11

• cant usually palpate the spleen, but with splenomegaly you can( feel under the right costal margin) before moving to the right iliac fossa where you can feel it, upon inspiration you can feel the spleen edge moving towards your hand, feel for the splenic notch,and measure the cm from the costal margin in the midclavicular line

Question 12

what should you advise people with splenomegaly

Answer 12

• not to do exercise because its large and not protected by the rib cage so high risk of getting ruptured

Question 13

MASSIVE, MODERATE, MILD causes of splenomegaly

Answer 13

• MASSIVE ; leukemia (e.g chronic myeloid leukiemia)/myelofibrosis/malaria/schistosomiasis (parasitic worm infection which destroys different organs inclusing spleen)
• MODERATE ; lymphoma ( blood cancer that develops from lymphocytes)/myeloproliferative disorders/liver cirrhosis wht portal hypertension/ infections like glandular fever(vial infection)
• MILD; infectious Hepatitis / Endocarditis/ Infiltrative diseases like sarcoidosis (formtion of granulomas v rare on spleen due to collection of inflammatory cells)/autoimmune diseases

Question 14

what’s hyposplenism?

what causes it?

and what do you see on film?

Answer 14

• lack of functioning splenic tissue
• splenectomy / sickle cell disease (infarcts and fibrosis)
• gastrointestinal diseases like crohns and coeliac and Ulcerative colitis (comprimsied immune system ^ infection risk/ excess loss of lymphocytes)
• autoimmune disordes like systeic lupus (body attacks normal tissue mistakenly)/ hashimotos disease
• Howell Jolly Bodies (DNA remenants because liver not F well so cant remove it completely)

Question 15

what are pateints from hyposplenism at a risk of?

how do we manage them?

Answer 15

sepsis from encapsulated bactiera like Streptococcus pneumonia, Haemophilus influenza, Meningococcus

(c invasive infections and spleen is the main organ involved in removing them)

• must vaccinate them against ^ and give them life long antibiotic prophylaxis (antibiotics given to prevent bacterial infection)

Question 16

histology of spleen label this

Answer 16

Question 17

activation of whatcell is thought to be associated with asthma?

what are monocytes and how long do they remain in the blood?

Answer 17

• eosinophils
• 1-3 days they remain in the blood and are capable of phagocytosis, before they are differentiate into dendritic cells or marcophages

Question 18

what is the life cycle of a B cells

Answer 18

• develops in the fetal liver where it comes into contact with pathogens and develops early immunoglobin genes allowing them to form an array of Antibodies, they then finally mature in the lymph nodes where they can recognise self and non-self antigens and produce alrge quanitites of antibodies.

Question 19

whats the life cycle of T cells

Answer 19

• arise from the liver and migrate to the thymus early in gestation, where they undergo rearrnagent of their T cell receptor genes giving them the ability to recongise a wide rangeof antigens that can be possibly presented by APC

Question 20

why do we look at reticulocyte count

Answer 20

gives good diagnostic estimate for amount of erythropoiesis

Question 21

why are RBC susciptable to Oxidative damage and energy production issues?

Answer 21

• it doesn’t have a nucleus (since it excrudes it) therefore cant replace damaged proteins by re-synthesis , just like in G-6-dehydrogenase deficiency disease, where d to v NADPHoxidative damge occurs to the Hb since it’s a protein, they aggregate and form Heinz bodies
• RBC rely on glycolysis for energy sicne they dont have a mitochondria , so any issue with glycolysis will result in damage to it, just like in Pyrivate kinase deificeny , can tmake energy via glycolysis so cant maintain cellular reaction or the membrane c haemolysis

Question 22

why is RBc shaped like that?

whats the membrane like? give example of disorder?

Answer 22

• optimised laminar flow properties of blood in large vessels and small ones
• spectrin, ankyrin, band3 and protein 4.2 =their role is to facilitate vertical interactions with the cytoskelton, and play a role in maintaining that concave shape
• hereditary spherocytosis; (recessive) issue with these proteins so not funcitonal membrane wc is excruded partly creating a spherical shape,

Question 23

^ 2,3 BPG ?

Answer 23

decrease affinity

Question 24

^ CO

Answer 24

^ affinity

Question 25

^ pH

Answer 25

v affinity b hb denatured cant even bind to 02

Question 26

what does the spleen do the RBC

Answer 26

• recycles the Hb; globin chains is degraded inot amino acids and haem is broken down into bilirubin which is removed by the liver where it is conjugates with glucuronic acid and secreted in bile, bacteria in the intestines deconjugate this and metabolise it into urobilinogen and it is oxidised to form stercobilin (brown poo colour),and then smaller amounts of urobilinogen is reabsorbed into b and processed by kidneys were oxidsed to urobilin (urine yellow colour)

Question 27

route of bilirubin and how to tell where the issue is with jaundice

Answer 27

• from spleen to the liver via the portal system and then into the gall bladder , where stored with cholesterol before spilled inot small intestine
• ^ Alakaline Phosphatase (ALT) means jaudince d blockage of gallbladder since that enzyme is produced there
• ^ALT/AST = liver damage itself so cant conjugate the bilirubin hence in the blood and jaudince