deck_15291969 Flashcards
pathogenesis of atherosclerosis
- endothelial injury → increased permeability → leukocyte adhesion & macrophage activation
- lipid deposition in damaged intima
- macrophages engulf lipids → lipid accumulation → fatty streaks (EARLY)
- macrophages secrete cytokines and growth factor → ECM synthesis esp collagen
- collagen synthesis forms dense fibrous cap over plaque → white & hard (ESTABLISHED)
- collagenisation affect tunica media → disrupt elastic intima
MI – how MI leads to pulmonary & ankle oedema
death of heart muscles → LV pump failure
backward failure → LA dilation → pulmonary hypertension → pulmonary congestion → pulmonary oedema
left side fail → RV failure → systemic & portal congestion → ankle oedema
complications of MI
Myocardial rupture
Congestive heart failure
Fibrosis
Aneurysm
Thrombus
Pericarditis
Ruptured papillary muscle
Arrhythmia
Contractile dysfunciton
modifiable risk factors of MI
smoking
hyperlipidemia
hypertension
diabetes
non-modifiable risk factors of MI
age
gender
family history
genetics
infective endocarditis (what? cause? symptoms?)
infection of valves
- acute: S aureus
- subacute: Viridans strep
form vegetation → destroy tissues
symptoms: fever, chills, heart murmur
rheumatic heart disease
abnormal immune response (to group A Strep Pharyngitis)
- inflammation & damage to heart valves → stenosis and regurgitation
causes of hyperthyroidism
primary: Graves, toxic multi nodular goitre, toxic neoplasm
secondary: pituitary hyperfunction
causes of hypothyroidism
primary: hashimoto (most common), iatrogenic
secondary: pituitary failure
cretinism (congenital in children) – dietary iodine deficiency
symptoms + biochemical signs of hyperthyroidism
weight loss
hot - heat intolerance
oligomenorrhoea (infrequent period)
diarrhoea
irritable mental state
increased appetites
high T3, T4
low TSH
symptoms + biochemical signs of hypothyroidism
weight gain
cold intolerance
menorrhagia (heavy period)
constipation
mental slowness
decreased appetite
low T3, T4
high TSH (primary), low TSH (secondary)
pathogenesis of graves
- autoantibodies bind & activate TSH receptor
- release of T3, T4
- increase cellularity & hyperplasia of gland
gross features of graves
- diffuse enlargement
- red meaty cut surface
- smooth & soft gland, intact capsule
histology:
- follicular cells tall, columnar, crowded – pseudopapillae
- inflammatory cells
gross features of hashimoto
- pale
- enlarged
histology:
- lymphoid follicles
- hurthle cell changes
which thyroid carcinoma metastasise via bloodstream
follicular carcinoma
which thyroid carcinoma metastasise via lymphatics (LN)
papillary carcinoma
medullary carcinoma associated with??
MEN (multiple endocrine neoplasia)
- younger patient
diagnosis for single thyroid nodule
follicular adenoma
follicular carcinoma
papillary carcinoma
anaplastic carcinoma
medullary carcinoma
features of papillary carcinoma
- nuclear features: finely dispersed chromatin, nuclear grooves, pseudo inclusions
- papillae with fibrovascular cores
- psammoma bodies
MEN 1 associated with which gene mutation
MENIN gene mutation
MEN 2 associated with which gene mutation
RET gene mutation
MEN 1 clinical feature
PHAIG
prolactinoma - excessive breast milk production
hyperparathyroidism - hypercalcemia
adrenal adenoma – cushing syndrome
insulinoma
gastrinoma - gastric ulceration
MEN 2B clinical feature
- mucosal neuroma syndrome (growth around nerves of mucous membranes)
- marfanoid syndrome (long limbs, loose joints, curved spine)
role of PTH
increase Ca levels by
- ↑ bone resorption by osteoblasts
- ↑ renal tubular absorption
- ↑ intestinal absorption (mediated by Vit D, PTH ↑ its synthesis)
causes of hyperparathyroidism
primary
- parathyroid adenoma (MOST COMMON) / carcinoma – 1 gland enlarged
- parathyroid hyperplasia – >1 glands enlarged
secondary
- renal failure (kidney too much phosphate reabsorption => form insoluble calcium phosphate => ↓ serum Ca2+ => ↑ PTH)
effects/consequences of parathyroidism
- renal & urinary calculi
- osteitis fibrous cystica
- hypertension
- pancreatitis
- peptic ulcer
- metastatic calcification
causes of hypoparathyroidism
iatrogenic (surgery)
autoimmune
causes of adrenal hyperfunction
primary
- adrenal adenoma/carcinoma
- adrenal hyperplasia
secondary
- pituitary adenoma
Cushing syndrome clinical features
cushing is due to increase in cortisol
- adrenal tumour/hyperplasia
- moon face, buffalo hump, obesity
- hyperglycaemia
- hypertension
- osteoporosis
- thin wrinkled skin, abdominal striae
- muscle weakness
- emotional disturbance
- skin ulcers (poor wound healing)
- amenorrhea
causes of adrenal hypofunction
primary
- iatrogenic (surgery)
- autoimmune
- haemorrhage (blood vessels in adrenal gland rupture)
- infections: TB, histoplasmosis
- metastatic tumours
secondary
- pituitary disease
effects of adrenal hypofunction
- weight loss
- muscle weakness
- low BP
- poor immune response
polycythaemia
too much RBCs
- associated with hypoxia – living at high altitudes
causes of anaemia
too few RBC
- decrease production: iron/B12/folate deficiencies
- bleeding
- increased destruction: Hb defects (sickle cell / thalassaemia), enzyme defects (G6PD)
symptoms of anaemia
pallor
weakness
dizziness/syncope
palpitation, chest pain, shortness of breath
leukocytosis – following associated with what
- neutrophilia
- eosinophilia
- monocytosis
- lymphocytosis
- neutrophilia: infection, tissue necrosis
- eosinophilia: allergies, parasitic infection
- monocytosis: chronic infections (eg. TB), autoimmune disease
- lymphocytosis: viral infections, TB
thrombocytosis – what? and causes
too many platelets
primary: neoplastic
secondary:
- hemorrhage
- splenectomy
- infections
- inflammatory conditions (autoimmune disease)
effects of thrombocytosis
thrombosis
bruising
bleeding
thrombocytopenia
too few platelets
caused by
- bone marrow damage (Chemo/radiotherapy),
- autoimmune disease
- hypersplenism (splenomegaly)
- increased consumption (shock, burns, sepsis)
effects of thrombocytopenia
- petechiae
- bruising
- bleeding (nose bleed; internal bleeds)
- prolonged bleeding
causes haemophilia (inherited/acquired)
inherited coagulation factor deficiency
- haemophilia A: factor 8
- haemophilia B: factor 9
- Von Willebrand’s disease: VW factor
acquired disorders:
- liver disease – ↓ clotting factor
- Vit K deficiency
leukemia types
ALL - acute lymphoblastic leukaemia: C1
CLL - chronic lymphoid leukaemia: A1
AML - acute myeloblastic leukaemia: C2, A1
CML - chronic myeloid leukaemia
clinical signs for benign vs malignant LN
BENIGN vs MALIGNANT
tender | non-tender
discrete | discrete/matted
small | large
mobile/bilateral | fixed to underlying structures
causes of benign lymphoma
- bacterial
- viral (EBV)
- granulomatous (TB, bartonella hanselae → cat-scratch disease)
- autoimmune disease (SLE)
- sarcoidosis
causes of malignant lymphoma
Primary: non-hodgkin lymphoma & Hodgkin lymphoma
secondary: metastasise from NPC, SCC, breast carcinoma
Identifying Source of Tumour for Tx
Type:
- Carcinomas tend to spread via lymphatics => LN metastasis more likely
- Sarcomas tend to spread via blood => LN metastasis less likely
Location of LN:
- Upper cervical: upper GIT, nasopharynx
- Supraclavicular: lung, breast
- Inguinal: external genital organs, lower limbs
Immunohistochemistry:
- Detect small deposits of tumour
- Distinguish btw primary & secondary tumours
- Specific markers (antibodies) to identify primary site of metastases
which lymphoma associated with EBV
hodgkin lymphoma
non-hodgkin lymphoma
- associated with which age group
- histo
- 2 peaks: young adults & elderly
- Reed Sternberg cell (OWL EYES)
gross features of SCC
masses of necrosis
ulcers with rolled margins
histo: keratinised growing pattern, atypia at base, irregular stromal invasion
risk factors of SCC
smoking, alcohol
tobacco chewing, betel nut chewing
HPV esp type 16
causes of chronic gastritis
- H. pylori
- autoimmune: pernicious anemia
- toxic: smoking/alcohol
- post surgical: bile reflux
H. pylori associated diseases
chronic gastritis
peptic ulcer
gastric carcinoma
gastric MALT lymphoma
pathogenesis of H. pylori
- colonisation damages epithelial and endothelial cells
- bacterial platelet-activating factor → thrombotic occlusion of capillaries
— produce urease: convert endogenous urea into free ammonia
— produce peptidase: break down glycoproteins in gastric mucus
— produce phospholipase: damage epithelial cells → may release bioactive leukotrienes - attract neutrophils, while releasing myeloperoxidase
- other antigens attract inflammatory cells → inflammation makes mucosa more susceptible to acid injury
- damaged mucosa more permeable → leakage of tissue nutrients → sustain bacteria
causes of peptic ulcer
H. pylori
smoking, alcohol
drugs: anti inflammatory and analgesics
complications of peptic ulcer
- bleeding: ulcer extended deeper into lining damages larger blood vessels
- perforation: leakage of GIT contents into abdominal cavity → inflammation & infection
- obstruction: oedema → obstruct pyloric canal/duodenum
- malignancy: adenocarcinoma
liver failure complications / clinical manifestations
- coagulapathy → easy bruising
- hepatic encephalopathy →impaired hepatic metabolism
- Cholestasis → jaundice
- portal hypertension → ascites, splenomegaly
cirrhosis
- what?
- causes
- histo
scarring/fibrosis of liver
causes:
- viral hepatitis
- DILI
- alcohol liver disease
- bile duct obstruction
histo:
- diffuse transformation of liver to regenerative parenchymal nodules
- surrounded by fibrous bands
- surrounded by variable degree of vascular shunting
pathogenesis of portal hypertension
(how cirrhosis → portal hypertension)
- increased resistance to portal flow
- vasoconstriction by vascular smooth muscles & myofibroblasts
- scarring/parenchymal nodules → disrupt blood flow
- sinusoidal remodelling & arterial-portal shunt (intrahepatic shunt) - increased portal venous flow
- due to hyperdynanamic circulation
- arterial vasodilation of splanchnic circulation (blood flow to abdominal GI organs)
consequences of portal hypertension
- ascites: increased pressure in peritoneal capillaries → fluid accumulation in peritoneal cavity → abdominal distension
- portosystemic venous shunts (varices) → bleeding
- congestive splenomegaly: back flow of blood into spleen → enlarge spleen
- hepatic encephalopathy: impaired metabolism → shunting of ammonia from GIT into circulation → ammonia alter mental state → asterixis, coma
viral hepatitis caused by
HEP A/B/C/D/E, EBV, CMV
- Acute liver failure w submassive/
massive hepatic necrosis
(usually Hep A/B/D, in pregnancy Hep E)
- May progress to cirrhosis
(usually Hep B/C)
Symptoms of Acute Hepatitis
- Jaundice, dark-coloured urine
- Fever, fatigue, poor appetite
- Nausea, vomiting, abdominal pain
Fatty Liver Disease Causes
- Diabetes, obesity, starvation
- Hypoxia
- Alcoholism
consequences of alcoholic liver disease
- Steatosis: accumulation of fat within liver
- Alcoholic hepatitis: inflammation due to fatty change
- Steatofibrosis
- May lead to cirrhosis (10-15%) => HCC (1-6%)
pathogenesis of NAFLD
non-alcoholic fatty liver disease
- insulin resistance → dysfunctional lipid metabolism
- increased production of pro inflammatory cytokines
- fat laden cells sensitive to peroxidase products → oxidative injury → liver cell necrosis
risk factors for HCC
- viral infection: HEP B/C
- toxin: aflatoxin from Aspergillus flavus
- metabolic diseases
NAFLD
hep b & c transmission via
- unprotected sex with infected
- needle prick injury / sharing needles
b: perinatal (transplacentally)
c: haemodialysis without infection control & organ transplant
histo for HCC
- trabecular (sinusoidal), pseudoacinar & compact growth patterns
- polygonal cells with, eosinophilic cytoplasm and distance round nucleus
- lack portal tracts, Kupffer cells and cohesive connective tissue framework
atelectasis
collapse of lung - inadequate expansion of lung
pneumonia
infective inflammation & consolidation of lung
- neutrophils in airspaces
risk factors of TB
- chronic lung disease
- HIV, AIDS, acute renal failure, disease
- alcoholism, malnutrition
gross features / histo for TB
- caseous necrosis → cavitation
- surrounding fibrosis
tuberculosis
chronic pneumonia
- communicable, granulomatous & caused by Mycobacterium TB
pneumonitis
inflammation dominated by interstitial inflammation
osteoarthritis
- what
- causes
- gross features/histo
chronic progressive degradation of articular cartilage
caused by wear and tear
- genetic abnormalities: familial mutation of type II collagen COL2A1
gross features:
- destruction of articular cartilage → narrowed joint space
- eburnation: loss of cartilage with smooth polished surface
- subchondral cyst formation
- osteophytes: peripheral growth of bone & cartilage
- reactive thickening of synovium
rheumatoid arthritis
- what
- causes
- gross features
systemic, chronic inflammatory autoimmune disease
causes:
- genetic predisposition (HLA-DR4)
- autoantibodies against cyclic citrullinated peptides (CCPs)
Gross features:
- synovial inflammation - swelling
- pannus formation - hypertrophied synovium & vascular granulation tissue
- destruction of adj bone (due to pannus)
- formation of rheumatoid nodules: granuloma w central zone of fibrinoid necrosis
pathogenesis of osteomyelitis
- bacterial proliferation in bone → acute inflammation & bone necrosis
- bacterial inflammation spread within bone shaft, haversian system & periosteum
- inflammation within periosteum → sizeable subperiosteal abscess “lifting” periosteum → impair blood supply → cause suppurative injury & further segmental sequestrum
- rupture of periosteum → abscess in surrounding soft tissue → form draining sinus
sequelae of osteomyelitis
- acute OM to chronic OM
- proliferative periostitis & involucrum
- pathologic fracture with deformities
- spread of inflammation/infection elsewhere
- bone abscess including Brodie’s abscess
- secondary amyloidosis (chronic OM)
gout
deposition of urate crystals & increased serum uric acid
osteosarcoma
produces malignant osteoid
- histo: cytological atypia
Ewing sarcoma
malignant
NO production of malignant osteoid
translocation of t(11,22)
chondrosarcoma
production of malignant cartilage
histo: cartilage matrix permeates/invades bone, marrow, soft tissue
chondroma
benign cartilage
osteochondroma
contain benign cartilage and bone
giant cell tumour
benign, epiphyseal-metaphyseal region
- abundant giant cell tumour (osteoclastic type)
fibro-osseous tumours
- type n comparison
Fibrous Dysplasia (FD) & Ossifying Fibroma (OF)
both: benign bone tumour; contains fibrous tissue & immature bone; same histo
OF vs FD
- FD has GNAS1 mutation
- radiology: OF more circumscribed
- OF higher potential of recurrence
clinical manifestations of increase inter cranial pressure (ICP)
- Papilledema (swelling of optic discs)
- cerebralherniation
- headache, nausea/vomiting
- macroencephaly
- altered mental status
- crushing triad: bradycardia, hypertension, repsiratory depression
pathogenesis of subdural haemorrhage
tearing of BRIDGING VEINS in subdural space → extravasation of venous blood
- slow progressive neurological deterioration
pathogenesis of subarachnoid haemorrhage
increase bp / trauma / spontaneous → rupture of BERRY ANEURYSM
pathogenesis of epidural haemorrhage
temporal skull bone fracture / trauma → laceration of MMA → extravasation of arterial blood
lucid for 2-3 hours → lose consciousness
intracerebral/intraparenchymal haemorrhage
hypertension → damage blood vessels → formation of micro-aneurysms
symptoms: headache, nausea, coma, fever, vomiting
if rupture → bleed within parenchyma → brain herniation → death
cells of innate and adaptive immune system
innate: macrophage, NK cells
adaptive: cell-mediated (T-cells), humoral (B cells & CD4 T cells)
alzheimer disease
- region affected, protein inclusions
- brain volume loss
- affects CEREBRAL CORTEX
- formation of protein inclusions
—- extracellular fibrillar Aβ plaques (beta-amyloid)
—- Intracellular neurofibrillary Tau tangles (Tau protein)
parkinson disease
- region affected, protein inclusions
- basal ganglia & brainstem
- degeneration of dopinergic neuron
- eosinophilic inclusions (Lewy bodies)
- proteins: α-Synuclein
hypertrophy - physiological causes
- sex organs - testosterone & oestrogen during puberty
- cardiac muscles - sustained high outflow (athletes)
- uterine muscles - oestrogen during puberty
- breast tissue - oestrogen & prolactin for lactation
- skeletal muscles - exercise
hypertrophy - pathological
- LV cardiac muscle - increased outflow pressure (systemic hypertension, aortic valve disease)
- RV cardiac muscle - increased outflow pressure (pulmonary hypertension, pulmonary valve disease)
arterial smooth muscle - hypertension
hyperplasia - physiological
- breast tissue - during puberty, pregnancy & lactations
- thyroid - increased metabolic demand during puberty & pregnancy
- stromal cells in endmetrium: oestrogen during pregnancy
- RBC precursors in bone marrow - erythropoietin at high altitudes
hyperplasia - pathological
- thyroid - graves (autoantibodies effect to TSH receptors
- stromal cells in endometrium - may lead to endometrial carcinoma
- skin - persistent trauma (eg corns on feet)
- parathyroid gland: hypocalcemia
- prostate gland
metaplasia
ciliated pseudostratified columnar → squamous
- respiratory tract of smokers
- chronic bronchitis
stratified squamous → simple columnar
- barrett’s oesophagus, gastro-oesophageal reflux
simple columnar → intestinal
- chronic gastritis
- H. pylori in stomach
causes of acute inflammation
- infection
- physical agent: mechanical, heat/cold, ionising radiation
- chemical agent
- ischaemia
- immunological reaction
