Metaplasia : one cell type changes to

another to cope up better with the stress.

Patho of Foundation and 2 types:
Blood ®SK epithelial metaplasia:
-squamous epithelial metaplasia:
changes in bronchus (smoking, ciliated
FOUNDATION
columnar epithelium changes to stratified
Cell adaptations: reversible changes in squamous cells) uterine, bladder etc.
shape, size, metabolic activity of cells in Epithelial metaplasia is a double edged
response to environmental changes. May sword: squamous epithelium copes up
be physiologic or pathologic. better with toxic substances in cigarette
5 types: hypertrophy, hyperplasia, smoke but protective cilia and mucus are
metaplasia, dysplasia, atrophy. lost.
-columnar epithelial metaplasia intestinal
Hypertrophy : cell size increase -> organ metaplasia in healed gastric ulcer and
size increase Barrett's esophagus.
Physiologic: uterus growth during mesenchymal metaplasia:
pregnancy, muscle hypertrophy due to -osseous
exercise -cartilaginous
Pathologic: heart hypertrophy due to
hypertension or valve disease. Dysplasia: disorderly growth of cells.
Also called atypical hyperplasia.
Hyperplasia : cell number increase -> Increased but unorganised layers of cells
organ size increase. Occurs when tissue in epithelium
has more of those cells that can replicate Example: in uterine cervix and bronchial
a lot. May occur along with hypertrophy. mucosa
Physiologic: hyperplasia of breast
epithelium at puberty or pregnancy, Apoptosis
pregnant uterus, prostatic hyperplasia(old Greek word meaning dropping/falling off
age), regeneration of liver after partial Energy dependent programmed cell death
hepatectomy, epidermis growth after skin Physiological causes: disappearance of
abrasion web tissues between fingers and toe in
Pathologic: hyperplasia of granulation embryonic life, endometrial cell breakdown
tissue in wound healing, skin warts during menstrual cycle, elimination of
neutrophils and leukocytes after immune
Atrophy : cell size decrease -> organ rxn ended
size decrease Pathologic causes: elimination of cells
Physiologic: fetal organs like notochord, with damaged DNA and misfolded
uterus after delivery, atrophy of thymus. proteins, killing of infected cells, rejection
Pathologic: starvation of transplantation.
atrophy(marasmus), denervation atrophy, Microscopic features: cell shrinkage,
ischemic atrophy, disuse atrophy of bones nuclear condensation and fragmentation,
and muscles, vaginal and breast atrophy apoptotic bodies and cytoplasmic blebs.
after menopause. Major players: apoptosis initiating factor,
In atrophy there's less protein synthesis, P53 gene, caspases etc
more degradation in cells. Atrophy is also
accompanied by autophagy sometimes. Phases of apoptosis:
1.Initiation phase: apoptosis initiated 2.Liquefactive necrosis: ischemic injury,
either by intrinsic/mitochondrial bacterial or fungal infection. Degradation
pathway(due to radiation) or of tissue occurs unlike coagulative. Organ:
extrinsic/death receptor brain
pathway(extracellular death ligands bind Digestion of dead cells leaving a liquid
to death receptors)-> caspases activated mass(pus)
-> apoptotic death. 3.Gangrenous necrosis: not a specific
2. Execution phase: caspases activate pattern of cell death but relevant to cell
DNase -> fragmentation of nuclei. death clinically. Usually limbs, specially
Apoptotic cell is then removed by lower legs, lose blood supply and undergo
phagocytosis. coagulative necrosis. When bacterial
Disorders of apoptosis may be due to infection also occurs on it, there is more
reduced apoptosis(cancer, autoimmune) liquefactive necrosis over tissue so called
or increased apoptosis(ischemia, "wet gangrene"
neurodegenerative disease) 4.Caseous necrosis: centre of foci of TB
infections. Features of both liquefactive
Necrosis and coagulative. Cheese-like appearance.
Irreversible cell injury leads to necrosis i.e 5.Fat necrosis: leakage of pancreatic
cell death. An "accidental" and lipases that liquefy the fat cell membranes.
unregulated cell death resulting from Released lipases split TAG esters -> fatty
damage to cell membranes and loss of ion acids -> combine with calcium to produce
homeostasis. When cell memb damage is chalky white areas(fat saponification)
severe, lysosomal enzymes enter Organ: pancreas(acute pancreatitis)
cytoplasm and digest the cells -> necrosis 6.Fibrinoid necrosis: antigen antibody
Necrotic cells can't maintain integrity of complexes deposited in artery walls.
membrane and their contents leak out, Examples: immune complex vasculitis
eliciting inflammatory responses. Fate of necrosis: some cells that are not
Morphology: eosinophilia on H&E staining, destroyed properly get calcified:
glassy homogeneous appearance, dystrophic calcification.
vacuolated cytoplasm, calcification of
dead cells.
Electron microscopy: BLOOD
Mitochondria dilated, membrane
discontinued, nuclear changes: Introduction to Anemia : decrease in O2
pyknosis(condensation i.e nuclear carrying capacity of blood.
shrinkage), karyorrhexis (nucleus Microcytic: Iron deficiency, lead
fragmentation) and karyolysis (loss of posioning, thalasemia, chronic anemia.
DNA, nuclear fading). Normocytic: after acyte blood loss, bone
Types of necrosis: marrow faliure.
1.coagulative necrosis: cell components Macrocytic: vit B12 and B9 deficiency.
are dead but tissue organisation is intact. -sickle cell anemia patients have leg
Most common type. Characteristics of ulcers.
infarcts. Organs: heart and kidney -thalasemia patients have bone
Hallmark of coagulative necrosis is the deformities.
conversion of normal cells to "tombstones" Iron deficiency Anemia :
i.e cell outlines are there but contents are Decreased rbcs or Hb due to reduced iron
lost. levels.
MCV, MCH, MCHC reduced. May be due and move towards the interstitium of
to more iron demand or less intake or injured tissue.
chronic blood loss. Cellular changes in acute inflammation:
Causes: ulcers, menorrhagia, CA cervix, margination, adhesion, emigration,
gastrectomy, hookworm infestation, piles chemotaxis, phagocytosis.
Pica: characteristic of this anemia. It Chronic inflammation
means desire to eat clay, paint, cardboard Start off insidiously ya as a continuation to
etc acute inflammation
Symptoms are weakness, fatigue, vertigo, Granulomatous rxn.
dyspnea, pallor of conjunctivae, fingernails In autoimmune and persistent
brittle and spoon shaped(koilonychia), infections
cracked edges of lips(angular chilosis), Silica: inflammatory lung disease silicosis
glossitis of tongue. Atherosclerosis: chronic inflammation of
Rbcs are hypochromic, micorcytic, artery wall
poikilocytes(pencil cells). Macrophages, lymphocytes
Megaloblastic Anemia: defective DNA Angiogenesis(healing)
synthesis result in large but microcytic Mediators: cytokines(TNF, ILs) and growth
cells. factors
Mainly due to B12 and B9 deficiency Granulomatous inflammation: form of
In strict vegetarians, pernicious anemia, chronic inf.. collection of
gastrectomy, H pylori infection. macrophages(resemble epithelial so
Clinical features: neurologic changes, called epitheloid cells), T cells and central
peripheral neuropathy(in B12 def), necrosis. (Capturing an agent that is tough
psychosis, dementia. to eradicate)
Hb, hematocrit reduced. Foreign body granuloma: inert foreign
MCV high bodies: talc, sutures, fibres
Anisocytosis, poikilocytosis, basophilic Immune granuloma: agents that induce
stippling and howell jelly bodies appeared cell mediated
in blood film. Non caseated granuloma: no central
Acute inflammation : necrosis: crohns disease, sarcoidosis
Early response of living tissue to injury. Caseous necrosis: central necrosis is
Delivery of WCBs to injury site. cheese like : agent like tb bacteria
Neutrophils and monocytes involved. Two types of WCBs disorders:
5 cardinal signs: proliferative(expansion of wbcs) and
color(heat) leukopenias(deficiency of WCBs)
Rubor(redness) Commonly theres neutropenia,
Tumor(swelling) granulocytopenia whereas
Dolor(pain) lymphopenia(HIV, COVID19, TB) is
Functio laesa(loss of function) uncommon.
Causes of acute inflammation: infection, NEUTROPENIA: less neutrophils, more
mechanical trauma, physical or chemical prone to bacterial and fungal infections.
change, foreign body invasion, Can be due to inadequate granulopoiesis
hypersensitivity rxns. (aplastic anemia, megaloblastic anemia,
Events: vascular and cellular. myelodysplasia, kostman syndrome jn
Vascular events in acute inflammation: which granulocytes cant differentiate) or
marked vasodilation Increased destruction(SLE, drugs,
Exudate: fluid, proteins and cells that leak splenomegaly)
from blood vessels due to vasodilation
Most common cause of agranulocytosis is May be fat, air, amniotic fluid, tumor or
drug toxicity(antimetabolites used in bone marrow pieces.
cancer treatment to suppress Pulmonary embolism: most common.
hemopoiesis) Embolus from deep vein thrombosis of leg
Acquired idiopathic neutropenia: May be few emboli, small size.. many
autoantibodies against neutrophil anitgens small emboli.. medium sized emboli or
Leukocytosis: wbcs increase. Rxn to large/massive.
inflammatory state. Systemic embolism: from intracardiac
Neutrophilia: indication of bacterial thrombi, aortic aneurysms, vegetations.
infection. Go towards lower limb
Lymphocytosis: result of viral infections. Fat embolism: long bone fracture, fat
Epstein barr virus from bone released in circulation, forms
Eosinophilia: increased eosinophils. embolus
Indicates parasitic or allergic rxn. Air embolism: more than 100 ml of blood
Rashes, itching, runny nose in allergy, needed to produce symptoms. Occurs in
diarrhea in parasitic inf. decompression sickness.. swimming up to
Thrombocytopenia: quantitate platelet too quickly after staying in water doesnt
disorder. Less platelets. Congenital, give nitrogen enough time to leave blood
aplastic anemia, chemotherapy, so it forms painful bubbles. Forms bends
splenomegaly, increased platelet destroy in joints.. also called caissons disease.
Thrombocytopenic purpura: bleeding Treatment: repressurise.
time prolonged but PT and PTT normal Amniotic fluid embolism: amniotic
Thrombotic thrombicytopenic purpura and fluid(containing squamous cells, hair, fat,
hemolytic uremic syndrome mucin) enter into uterine venous
Thrombosis: hemostasis zyda hojaegi circulation. May cause occlusion in
Virchow triad: abnormally reduced blood pulmonary vessels.
flow, hypercoagulability, endothelial injury. Immediate transfusion rxns:
Endothelial injury: direct damage or Blood transfusion: transfer of blood from
imbalance in pro and anticoagulants one to another person through IV line.
Smoking, turbulent flow, Indications:
hypercholestrolemia Whole blood: acute blood loss and shock
Venous thrombosis, post MI thrombi Packed rbcs: chronic anemia, thalesemia
Protjrombin gene mutation, 8,9,11 or Platelets: thrombocytopenia
fibrinogen increased Fresh frozen plasma: von willebrand's
Arterial(white thrombi)or cardiac thrombi disease
begin at sites of turbulence or injury Pre transfusion testing: blood grouping
Venous (red thrombi) occur at stasis and cross matching.
Lines of zahn: pale platelet and fibrin Cross matching is taking donors serum
deposit alternating with darker red cell rich and recipients rbcs to see if they
layers agglutinate.
Present in antemortem clots nd absent in Compatible only if no agglutination occurs.
postmortem Pretransfusion checkup: BP, Pulse, resp
Vegetations are theombi on heart valves. rate, temperature.
Embolism: dislodged intravascular mass Transfusion rxn: unfavourable, harmful
carried by blood to site distant from origin rxn occuring after transfusion due to
point. incompatibility.
Majority emboli come from dislodged
embolus.
May occur due to wrong labelling, wrong human platelet antigen by pregnancy is re
blood issued, error in grouping nd cross exposed via this transfusion.
matching, blood contamination. -iron overload also occurs in delayed
Two types of transfuion rxns: transfusion rxns.
1.acute -Transfusion transmitted infections:
-hemolytic transfusion rxn(AHTR): hepatitis B, C, HIV, syphilis, malaria
incompatible rbcs, intravascular Hypersensitivity: immune response that
hemolysis,symptoms occur leads to exaggerated reactions that r
within minutes, labelling error is common, harmful to host.
can be fatal. Types: Gells and coombs classification:
Fever, chills, nausea, tachycardia, I,II,II: antibody mediated
dyspnea. IV: T cell mediated
-febrile(non hemolytic) transfusion Type I: allergic rxn, immediately following
rxn(FNHTR): within 4 hrs symptoms contact wid antigen, igE response, occur
appear. Temperature increase but no within minutes, IgE bind to mast cells nd
hemolysis. basophils -> degranulation occurs ->
-Transfusion associated lung histamine, prostaglandins, leukotreins
injury(TRALI): onset within 6 hrs. Donor released ->anaphylactic shock
antibody reacts with recipient neutrophil On frst exposure, T cells stimulate B cells
causing acute lung injury. Dyspnea and to produce igE antibodies which initiate
resp faliure. type I hypersensitivity in response to
Blood infusion should be slow rated bcz second exposure.
circulatory load may occurs in transfusion Examples: hay fever, bronchospasm, food,
rxns. pollen, house dust allergy, rhinitis,
2.Delayed conjunctivitis, utricaria, eczema avoid
Occurs after 24 hrs of transfusion allergen, give antihistamine,
-delayed hemolytic transfusion rxn(DHTR): bronchodilators.
new rbc antibodies detected after 24 hrs, Type II: also called tissue
mild. specific/cytotoxic hypersensitivity.
Occurs in patients who already had Antibodies produced by immune response
antibodies but they were too weak to be bind to antigens on patient's own cells,
found during pre transfusion testing. Only IgG and IgM bind to antigens ->
sign is unexpected sudden Hb drop. complement system activated. This rxn
jaundice nd fever also occur. takes hrs to days.
-transfusion associated graft vs host Examples: erythroblastosis fetalis
disease(TA-GVHD): delayed immune Drug induced hemolytic
response due to attack of late donor anemia(streptomycin, penicillin), acute
lymphocytes against recipient cells. graft rejection
Maculopapular rashes, diarrhea. 3 Direct antiglobulin test(Coomb's test):
conditions for TA GVHD: HLA antigen Detects antibody on patient's erythrocytes.
difference in donor nd recipient, donor If antibody us present, erythrocytes can be
immunocompetent cells present in blood, agglutinates by anti-human Ig.
recipient incapable of rejecting donor Type III: also called immune complex
immunocompetency hypersensitivity bcz in this, immune
-post transfusion pupura: complex activates
thrombocytopenia. Occur when patient is inflammatory response in tissues which
previously sensitized to are normally removed by monocyte
macrophage system
but in this, they persist and deposit in
tissues.
Mechanism: antigen binds to antibody ->
this complex deposits in tissue -> PMN
cells attracted to the site -> inflammation
Examples: insect bite, cheese workers
lung, wood workers lung, pneumonitis,
farmers lung, wheat miller's lung, tetanus
vaccine autoimmune diseases( RA, SLE,
post streptococcal glomerulonephritis),
serum sickness
Type IV: delayed hypersensitivity.
Appears 48-72 hrs after antigen exposure.
T cells and macrophages involved rather
than antibodies.
Examples: chronic graft rejections, latex,
nickel, poison ivy, tuberculin skin tests,
soaps, drugs, heavy metal jewelry

© SANDEEP BHAGWANI