Histopathology Flashcards

Question

What is hypertensive nephropathy?

Answer 1

•Pathophysiology is not fully understood * •Narrowing of arteries and arterioles leading to scarring and ischaemia of glomeruli * •Hypertension in glomeruli leading to altered haemodynamic environment, stress and segmental scarring * Shrunken kidneys with granular cortices * Histopathology may show “nephrosclerosis” * •Arteriolar hyalinosis, arterial intimal thickening, ischaemic glomerular changes, segmental and global glomerulosclerosis •HTN can be causative or consequential

Answer 2

* SLE is a systemic autoimmune disease * Affects the kidney, skin, joints, heart, serosal surfaces and the central nervous system * Affects around 1 in 2500 people and is nine times more common in females than in males * Deposition of immune complexes in the kidney is common * •Antibodies directed at a broad range of intracellular and extracellular antigens * •Anti-nuclear and Anti-dsDNA antibodies are typical Classification of lupus nephritis based on ISN/RPS classification Highly variable disease Depending on site, speed and intensity of immune complex deposition, may present as: * •Acute Renal Failure * •Nephrotic Syndrome * •Isolated Urinary Abnormality * •Chronic Kidney Disease

Answer 3

•Crystal aggregates that form in the renal collecting ducts * •May be deposited anywhere in the urinary tract * Lifetime incidence 15% * Males three times more likely to be affected than females * Stones can be made of: * •Calcium Oxalate (Weddellite) – 75% * •Calcium oxalate stones are related to hypercalciuria * •Absorptive hypercalciuria – excessive calcium absorption from gut * •Renal hypercalciuria – impaired absorption of calcium in proximal renal tubule * •Hypercalcaemia – primary hyperparathyroidism * •Rare * •Magnesium Ammonium Phosphate (Struvite) – 15% * also known as ”triple stones” * •Form as a consequence of infection with urease-producing organisms * •Proteus sp. * •Ammonia alkalinises urine – precipitation of magnesium ammonium phosphate salts follows * become very large indeed - "Staghorn Calculi” * •Uric Acid – 5% * •Uric acid stones may form in patients with hyperuricaemia * •Gout * •Rapid cell turnover * •Most patients do not actually have hyperuricaemia or increased uric acid excretion in urine * •Believed to be due to tendency to produce slightly acidic urine Complications: * •Small stones that stay in the kidney may be largely asymptomatic * •Otherwise detected during investigation of haematuria or recurrent urinary tract infection * •Small stones that drift out of the kidney may become impacted and cause colic and pain * •Pelvi-ureteric junction, pelvic brim, vesico-ureteric junction * •Large stones tend to stay in the kidney * •Obstruction, risk of infection, chronic renal failure, reflux nephropathy

Answer 4

_Papillary adenoma:_ * •Benign epithelial kidney tumour composed of papillae and / or tubules * •By definition, 15mm or less in size – regarded as benign, can see these in end stage cystic kidney * •Well-circumscribed * •Trisomy 7, Trisomy 17, Loss of Y chromosome * •Frequent incidental finding in nephrectomies and at autopsy * •Especially in chronic kidney disease, acquired cystic renal disease _Renal Oncocytoma:_ * •Benign epithelial kidney tumour composed of oncocytic cells * •Well-circumscribed * •Usually sporadic * •Can be seen in Birt-Hogg-Dubé syndrome * •Usually an incidental finding _Angiomyolipoma:_ * •Benign mesenchymal kidney tumour composed of thick-walled blood vessels, smooth muscle and fat * •Derived from perivascular epithelioid cells * •Mostly sporadic * •Can be seen in tuberous sclerosis * Quite a fat-rich tumour, which may not be apparent on XR * •Usually an incidental finding * •Larger tumours (\> 4cm) may present with flank pain, haemorrhage, shock, quite a vascular tumour hence the presentation

Answer 5

_Renal Cell carcinoma:_ * •Malignant epithelial kidney tumour * •Accounts for 2% of cancers worldwide * •More common in developed countries * •10 per 100,000 men, 3 per 100,000 women * •Risk factors include: * •Smoking * •Hypertension * •Obesity * •Long-Term Dialysis * •Genetic Syndromes – von Hippel Lindau * •Half of cases present with painless haematuria * •Most of the remaining cases are detected incidentally on imaging * •Small proportion present with metastatic disease * •Various subtypes are recognised * _•Clear Cell Renal Cell Carcinoma (70%)_ * •Epithelial kidney tumour composed of nests of clear cells set in a delicate capillary vascular network * •Appears grossly as a golden yellow tumour with haemorrhagic areas * •Genetically shows loss of chromosome 3p * Graded based on nuclei; can adopt a sarcomatoid morphology; but if a small nuclei has better prognosis * _•Papillary Renal Cell Carcinoma (15%)_ * •Epithelial kidney tumour composed of papillae and / or tubules * •By definition, more than 15mm in size * •Genetically shows trisomy 7, trisomy 17 and loss of Y chromosome * •Subdivided into two types based on morphology * •Grossly appears as a fragile, friable brown tumour * Looking at the papillary end on – pinker cells, with flecks of calcium in the tumour; looks vascular and appears to be a neoplasm * _•Chromophobe Renal Cell Carcinoma (5%)_ * •Epithelial kidney tumour composed of sheets of large cells that display distinct cell borders, reticular cytoplasm and a thick-walled vascular network * •Shows variable genetic aberrations * •Very mixed group * •Grossly appears as a well-circumscribed solid brown tumour * * •Remaining 10% are various rare subtypes Diagnosis: * •Five year survival across all tumour types is 60% * •Staging and Grading are most important prognostic factors * •ISUP Nuclear Grade (1-4) applies to clear cell and papillary renal cell carcinoma * •TNM 8th Ed. * •If it is big, punching out of the borders high stage * •If small and no necrotic centre then it is low stage * •For Clear Cell Renal Cell Carcinoma there is also a risk progression index * •Leibovich Risk Model (low risk, intermediate risk, high risk) _Nephroblastoma:_ * •Also known as Wilm’s Tumour * •Malignant triphasic kidney tumour of childhood * •Blastema (small round blue cells) * •Epithelial * •Stromal * •Typically presents as an abdominal mass in children aged 2-5 years old * •1 in 8,000 – second most common childhood malignancy * •95% of cases show favourable histological features with excellent prognosis

Answer 6

* •Also known as Transitional Cell Carcinomas * •Group of malignant epithelial neoplasms arising in urothelial tract * •Bladder * •Renal Pelvis * •Ureters * •Very common * •Smoking * •Aromatic amines * •Broad range of ages * •Most present with haematuria * •Three main subtypes * _•Non-Invasive Papillary Urothelial Carcinom_a * __Appear as frond-like growths (like cauliflower) * •Divided into low grade and high grade (WHO 2004) based on nuclear atypia * •Low grade tumours have a low risk of progression to invasive disease (\<5%) * •High grade tumours carry a higher risk of progression to invasive disease * •Unstable, carry a number of genetic aberrations including in RB and TP53 * •Very aggressive and progress very quickly – tp53 * More solid tumour in high grade * Low is more like weeds, and isn’t going to kill the pt in itself; high grade will be problematic * * _•Infiltrating Urothelial Carcinoma_ * •Urothelial tumour displaying invasive behaviour * •Wide range of subtypes * •Can take on many appearances; can know whether the chemo is going to work * •Once the first one has spread and changed appearance, you won’t be able to find the correct primary tumour * •Treatment based on depth of invasion * •Lamina propria * •Muscularis propria * * _•Flat Urothelial Carcinoma in-situ_ * •May be invisible or appear as a reddish area * •Flat urothelial lesion with unequivocal high grade features * •High risk of progression * •Terminology can be confusing

Answer 7

* •Benign enlargement of prostate as a consequence of increase in cell number * •Very common – symptomatic in 25% of men by age 80 * •Histologically present in 90% of men by age 80 * •Aetiology is not clear * •Increased oestrogen levels in blood, which rises with age, may induce androgen receptors and stimulate hyperplasia * •Treatment based on alpha blockers and 5⍺-reductase inhibitors as well as transurethral resection * •Presents with “Lower Urinary Tract Symptoms” * •Frequency * •Nocturia * •Urgency * •Hesitancy * •Poor flow * •Terminal Dribbling * •May also present with urinary tract infection, acute urinary retention or renal failure

Answer 8

* •Malignant epithelial prostate tumour * •Most common malignant tumour in men * •25% of all male cancers * •1 in 8 men will develop it in their lifetime * •Less prominent (but important) cause of cancer-related death * •Association with red meat consumption * •5-10x risk increase if first degree relative is also affected * •Arises from Prostatic Intraepithelial Neoplasia * •Mutations in PTEN, _AMACR_, GST-pi, p27 and more…; learn AMACR as now we have a stain to discover this gene * •Usually asymptomatic; usually diagnosed on biopsy following raised serum prostate-specific antigen or digital rectal examination * •May have lower urinary tract symptoms * •Rarely may present with metastatic disease * •Pathological fracture Diagnosis: * •Most powerful prognostic indicator is the Gleason score * •Influences treatment decisions * •Expressed as x + y = z * •Two most common patterns (or most common pattern and worst pattern in biopsy setting) * •Patterns range from 1-5 * •1 and 2 rarely if ever diagnosed so scores typically range from 6-10 * •Higher scores correlate with aggressive behaviour * •High volume tumours scoring 8-10 in particular * •Grade grouping used as well Image: top = grade 1,2,3; middle = grade 4; bottom = grade 5

Answer 9

* •Tumours of the testis arising from germ cells * •Account for 90% of testicular tumours * •Typically arise in men aged 20-45 * •Risk factors include * •Undescended testis (3-5x increased risk) * •Low birth weight / small for gestational age * •Malignant tumours arise from Germ Cell Neoplasia in-situ * •Process likely begins in foetal life * •Amplification of i12p * •Present as painless lump * •10% present with symptoms related to metastasis; paraaortic lymph nodes are the drainage system * •Back pain * •Cough * •Dyspnoea * •Five histological subtypes: * _seminoma_ * tend to have a fibrous background with all lymphocytes; polygonal cells with lymphoid filtrate * _embryonal carcinoma_ * anaplastic cells; necrotic tumour * _yolk sac tumour_ * very difficult to determine__ * _post-pubertal teratoma_ * malignant disease, cartilage/skin formation; can create it’s own cancer on the new different types of cells * _choriocarcinoma_ * __very high hCG levels in the blood * •Single tumour may be purely one subtype or contain a mixture of multiple subtypes Treatment: * •Highly sensitive to platinum-based chemotherapy regimes * •Prognosis excellent * •Five year survival is 98% in most countries

Answer 10

* •Much less common than germ cell tumours * _•Lymphoma_ * •Older men, 5% of all testicular tumours * •Highly aggressive; poor survival rates * •_Leydig Cell Tumour_ * •3% of all testicular tumours * •May present with precocious puberty if pre-pubertal * •Usually benign * •_Sertoli Cell Tumour_ * •1% of testicular tumours * •90% are benign

Answer 11

* •Epididymal cyst * •Epididymitis * •Usually related to C. trachomatis or N. gonnorrhoeae in men under 35; E. coli in men over 35 * •Varicocele * •Dilated venous plexus * •Hydrocele * •Fluid between layers of tunica vaginalis * •Adenomatoid Tumour * •Small tubules lined by mesothelial cells

Answer 12

* •Lichen Sclerosus / Balanitis Xerotica Obliterans * •Inflammatory condition that causes phimosis * •Zoon’s balanitis * •Inflammatory condition that causes red areas * •Condylomas * •HPV 6 and 11 * •Peyronie’s Disease * •Scarring , inflammation, thickening of corpus cavernosa * •Penile carcinoma * •Rare, elderly men * •Smoking, HPV, chronic Lichen Sclerosus are risk factors

Answer 13

* •Urethritis * •N. gonorrhoeae, C. trachomatis * •Prostatic Urethral Polyp * •Papillary lesion in prostatic urethra * •Urethral Caruncle * •Common lesion at urethral meatus in women * •Urethral Carcinoma * •Rare, more common in women, usually squamous cell carcinoma * •Malignant Melanoma * •Rare

Answer 14

* •Epidermoid Cyst * •Common * •Scrotal Calcinosis * •Rare; may be related to old epidermoid cysts * •Angiokeratomas * •Benign vascular lesions * •Fournier’s Gangrene * •Necrotising fasciitis; mortality of 15-20% * •Scrotal squamous cell carcinoma * •Very rare * •Historical interest; chimney sweep

Answer 15

•Opportunistic Infections * •Pneumocystis jiroveci: pneumonia * •CMV: especially retina and GIT - oesophagitis wth oesophageal ulcer and nuclear inclusion * •Candida * •Tuberculosis and atypical mycobacteria * •Cryptococcus: meningitis * •Toxoplasma gondii: encephalitis and mass lesions * •JC papovavirus: progressive multifocal leukoencepalopathy * •Herpes simplex * •Cryptosporidium, Isospora belli, microsporidia: GIT •Tumours * •Kaposi’s sarcoma: * HHV-8 * A.The dermis is expanded by a solid tumour. * B. Fascicles of relatively monomorphic spindled cells, with slit-like vascular channels containing erythrocytes. * C.The nuclei of the tumour cells demonstrate immunoreactivity for HHV-8. * •Lymphoma: * systemic, CNS or body cavity based * B cell lymphomas * EBV * •Others: * Squamous cell carcinoma * Anus and cervix * HPV •Central nervous system diseases * •Progressive encephalopathy = AIDS dementia complex * •Plus opportunistic infections and tumours * CNS lymphoma: are immunosuppressed so wouldn’t have as many wbc as a normal person would Image: Normal course of disease without disease modifying drugs; only in last few years do you get syx in the patient; have a flu-like syndrome at the beginning after the 1st infection

Answer 16

* Caseating granulomas - TB * Demonstration of acid fast bacilli – just because you don’t see them, doesn’t mean it isn’t TB Sites affected: * •Lung * •Lymph node * •Bone: e.g. vertebra * •Heart: e.g. pericarditis * •GIT: e.g. peritonitis * •CNS: e.g. meningitis * etc

Answer 17

* Non-caseating granulomas – firm and solid granuloma * A diagnosis of exclusion. * Cuff of lymphocytes round the outside, with no caseating necrotic centre Sites: * •Lung: scattered granulomas, heal with fibrosis * •Lymph nodes: usually hilar and mediastinal * •Spleen * •Liver * •Heart * •Joints * •Bone marrow * •Skin: nodules, plaques or macules * •Eyes: iritis, choroid retinitis, lacrimal glands * •CNS * •Salivary glands

Answer 18

* Inflammation dominated by IgG4 antibody producing plasma cells * Fibrosis, obliteration of veins * Damaging, inflammatory process but NOT an infection Diseases: * •Salivary and lacrimal glands: Mikulicz syndrome * •Thyroid: Riedel thyroiditis * •Peritoneum: Retroperitoneal fibrosis * •Liver: Biliary obstruction * •Pancreas: Autoimmune pancreatitis * •Mass lesions: Inflammatory pseudotumour

Answer 19

* •Liver: fatty change (steatosis) , fatty liver hepatitis (steatohepatitis),(fibrosis in between) cirrhosis (alcohol main cause in UK but can be caused by other things), liver cell cancer (hepatocellular carcinoma) * •GI Tract: acute gastritis, oesophageal varices * •Nervous system: peripheral neuropathy, Wernicke-Korsakoff syndrome etc. * •Cardiovascular system: dilated cardiomyopathy, hypertension, atheroma (and decreases it!) * •Pancreas: acute pancreatitis, chronic pancreatitis * •Fetal alcohol syndrome * •Cancer: oral cavity, pharynx. oesophagus, liver and breast

Answer 20

* Pancreas: duct obstruction, exocrine atrophy * Salivary glands: duct obstruction, atrophy * Intestine: meconium ileus * Liver: biliary obstruction, cirrhosis * Lung: bronchial obstruction, superimposed infection with abscess formation (Staphylococcus aureus, Haemophilus influenzae and Pseudomonas aeruginosa) * Male genital tract: infertility, absence of the vas deferens

Answer 21

* Deposition of an abnormal proteinaceous substance in non branching fibrils, 7.5-10nm diameter * Always contains P component * Beta-pleated sheet structure * A variety of proteins can take on this conformation * Resistant to enzymic degradation Classification: * By AA/AL: * •AA - derived from serum amyloid A – chronic inflammatory diseases * e.g. Crohn’s Disease, Rheumatoid arthritis * •AL - derived from light chains * e.g. multiple myeloma, B Cell lymphoma * •Transthyretin e.g. mutation * •Beta2-macroglobulin – peritoneal dialysis * •Abeta2 protein - Alzheimer’s * •Insulin, calcitonin – endocrine tumours * •The symptoms it causes are dependent on where it is deposited Staining: * •Stains with **_Congo Red dye_** * •This shows **_apple green birefringence_** under polarised light Clinical features: * •Proteinuria, renal failure * •Restrictive cardiomyopathy, arrhythmias * •Autonomic neuropathy * •Carpal tunnel syndrome * •Macroglossia * •Bleeding on injury * •Also deposited in blood vessels, endocrine organs, liver, spleen * •Deposits a plastic like substance in different parts of the body

Answer 22

An arteriosclerosis characterized by atheromatous deposits in and fibrosis of the inner layer of the arteries Atherosclerosis characterized by intimal lesions - atheroma (atheromatous plaques) - that protrude into vessel lumen Prothrombogenic so forms a clot which can block the artery or releases a clot – which causes ischaemia and death of the muscle and tissue beyond this. _Arethomatous plaque:_ * •Raised lesion * •Soft lipid core * •White fibrous cap _RF:_ * Age - progressive between 40-\>60yr, with MI incidence 5x higher * Gender - postmenopausal women increased risk as with men * Genetics - FHx most significant RF, some mendelian disorders but most are multifactorial * Hyperlipidaemia - diet rich in cholesterol/saturated fat = bad * Hypertension - alone increases risk by 60% * Smoking - definite in men, prolonged 2x risk of death from IHD, stopping reduces risk considerably * Diabetes Mellitus - induces hypercholesterolaemia, increases risk of atherosclerosis, 2x rsk IHD in DM * Have a multiplicative effect - 2 risk factors, increase risk 4x * Others: * •Inflammation * •Hyperhomocyteinaemia * •Metabolic syndrome * •Lipoprotein (a) * •Haemostasis (procoagulation) * •Lack of exercise * •Stress * •Obesity (Ht, Dm, low HDL) _Pathogenesis:_ * response to injury: * chronic inflammatory and healing response of arterial wall to endothelial injury * •Endothelial injury * •Lipoprotien accumulation (LDL) * •Monocyte adhesion to endothelium * •Monocyte migration into intima -\> macrophages & foam cells * •Platelet adhesion * •Factor release * •Smooth muscle cell recruitment * •Lipid accumulation -\> extra & intracellular, macrophages & smooth muscle cells * _Endothelial injury:_ * •Early atheroma arises in intact endothelium * •Endothelial dysfunction important – increase permeability, gene expression & adhesion * •Haemodynamic disturbance -\> dysfunction * •Hypercholesterolaemia -\> dysfunction * •Inflammation -\> vicious circle * _Smooth muscle proliferation:_ * •Intimal smooth muscle proliferation * •Some from circulating precursors – (have synthetic & proliferative phenotype) * •ECM matrix deposition * Fatty streak -\> mature atheroma & growth * •Earliest lesion * •Lipid filled foamy macrophages * •No flow disturbance * •In virtually all children \>10yrs * •Relationship to plaques uncertain * •Same sites as plaques * •PDGF, FGF, TGF-alpha implicated * _Infection:_ * __Herpes, CMV, chlamydia pneumonia * no conclusive evidence Atherosclerotic plaque: * •Patchy – local flow disturbances * •Only involve portion of wall * •Rarely circumferential * •Appear eccentric * •Composed of – cells, lipid, matrix * It can obstruct or rupture

Answer 23

* •Lots foam cells or extracellular lipid * •Thin fibrous cap * •Few smooth muscle cells * •Clusters inflammatory cells * •More likely to rupture and clot * •Adrenaline increases blood pressure & causes vasoconstriction * •Increases physical stress on plaque * •Hence emotional stress increases risk of sudden death * •Circadian periodicity to sudden death (6am-noon) * •Not all rupture causes occlusion * •Plaque disruption with platelet aggregation & thrombosis probably common * •Important mechanism for plaque growth

Answer 24

•_Stenosis_ * Critical stenosis – demand \> supply * Occurs at ~70% occlusion – in normal everyday life scenario * (or diameter \<1mm) * Causes “stable” angina at this level * Can lead to Chronic Ischaemic Heart Disease * Acute plaque rupture can occur _•Acute Plaque Change_ * Rupture – exposes prothrombogenic plaque contents * Erosion - exposes prothrombogenic subendothelial basement membrane * Haemorrhage into plaque – increase size * Either breaks and ruptures or makes it increase in size * •Majority of plaques that show acute change show only mild to moderate luminal stenosis prior to acute change * •Therefore numerous “asymptomatic potential victims” * •Plaques dynamic

Answer 25

* Reduces luminal size * Increases local mechanical forces -\> plaque disruption * Occurs due to: * - Adrenergic agonists * - Platelet contents * - Reduced endothelial relaxing factors * - Mediators from perivascular cells

Answer 26

* •Leading cause of death worldwide for men and women (7million/year) * •Group of conditions resulting from myocardial ischaemia * •Imbalance of supply to demand for oxygenated blood * •Also less nutrients & less waste removal it is important to remove the waste as it is a lethal combination with no O2 * •Therefore less well tolerated than pure hypoxia * •90% myocardial ischaemia due to reduced blood flow due to atherosclerosis * •Long silent progression prior to symptoms * •Fall due to prevention & treatment * •But aging population * •Decrease in rate due to changes in lifestyle and awareness Presentation: * •Angina pectoris * •Myocardial infarction * •Chronic IHD with heart failure * •Sudden cardiac death. Pathogenesis: * •Predominant cause is insufficient coronary perfusion relative to myocardial demand due to chronic progressive atherosclerotic narrowing of epicardial coronary arteries and variable degrees of superimposed plaque change, thrombosis and vasospasm * •\>90% have atherosclerosis of 1 or more epicardial coronary arteries * •75% stenosis or more generally needed to cause symptoms precipitated by exercise * •Vasodilation cannot compensate above this level of stenosis * •90% stenosis can lead to pain at rest * Plaques mainly in first few cm of LAD or LCX * Entire length of RCA can be covered in plaques

Answer 27

_•Stable plaque becomes unstable_ * •Due to rupture, erosion, haemorrhage etc * •Generally leads to superimposed thrombus which increases occlusion * Examples: * _Angina pectoris:_ * •Transient ischaemia not producing myocyte necrosis * •Stable, Prinzmetal,Unstable * •Stable comes on with exertion, relieved by rest, no plaque disruption * •Prinzmetal Uncommon, due to artery spasm * _Unstable angina pectoris:_ * •Unstable more frequent, longer, onset with less exertion or at rest * •Disruption of plaque due to superimposed thrombus * •Possible embolisation or vasospasm * •Warning of impending infarction _MI:_ * •Death of cardiac muscle due to prolonged ischaemia * •Incidence 5/1000 per year UK (ST elevation) * •10% less than 40yrs * •45% less than 65yrs * •Blacks & whites equal * •Men greater risk than women throughout life * •IHD most common cause death postmenopausal women * Pathogenesis: * sudden change to plaque, platelet aggregation * vasospasm, coagulation * thrombus evolves * Myocardial response: * •Myocardial blood supply compromised leading to ischaemia * •Loss of contractility within 60 seconds * •Therefore heart failure can precede myocyte death * •Potentially reversible * •Irreversible after 20-30 minutes * LAD - 50%, ant wall LV, ant septum, apex * RCA - 40%, post wall LV, post septum, post RV * LCx - 20%, lat LV not apex * Morphology: gross then micro * 1-18h - none + none * 24h - pale, oedema + oedema, inflammation * 3-4d - haemorrhage + necrosis, granulation * 1-3wks - thin, yellow + granulation tissue * 3-6wks - tough, white + dense fibrosis * Pathology: * Under 6 hours – normal by histology (CK-MB also normal) * 6–24 hrs loss of nuclei, homogenous cytoplasm necrotic cell death; Coagulation necrosis, loss nuclei & striations, neutrophils +++ which damage the myocardium * 1-4 days – infiltration of polymorphs then macrophages (clear up debris) * 5-10 days removal of debris * 1-2 weeks granulation tissue, new blood vessels, myofibroblasts, collagen synthesis * Weeks-months strengthening, decellularising scar * Clinical features: * •10 – 15% asymptomatic * •Common in elderly & diabetes mellitus * •Cardiac enzymes (CK, Troponin etc) * •Subendocardial infarct may not cause usual ST changes * Consequences: * •In hospital death rate 7% down from 30% in 1960s * •½ deaths occur within 1 hr of onset * •Most of them do not reach hospital * •Age, female, DM, previous MI -\> worse prognosis

Answer 28

* Clinical importance uncertain * Due to oxidative stress, Ca overload, inflammation * Arrhythmias common * Biochemical abnormalities last days -\> weeks * Thought to cause “stunned myocardium” – reversible cardiac failure lasting several days Hibernating myocardium: * •Chronic sub lethal ischaemia -\> lowered metabolism in myocytes “hibernating myocardium” reversed with revascularisation

Answer 29

* •Contractile dysfunction – 40% infarct-\> cardiogenic shock with 70% mortality rate * •Arrhythmia due to myocardial irritability & conduction disturbance – most reasons why people die after MI * •Myocardial rupture - free wall most common, septum less common, papillary muscle least common. * (At mean 4-5days, range 1-10 days) * •Pericarditis (Dressler syndrome) 2nd or 3rd day * •RV infarction * •Infarct extension – new necrosis adjacent to old * •Infarct expansion – necrotic muscle stretches -\>mural thrombus * •Mural thrombus * •Ventricular aneurysm, late -\> thrombus, heart failure, arrhythmia, do not rupture * •Papillary muscle rupture * •Chronic Ischaemic Heart Disease (Chronic IHD) = progressive late heart failure; tired, SOB, can’t do anything

Answer 30

* •Progressive heart failure due to ischaemic myocardial damage * •May not be prior infarction * •Can arise with severe obstructive coronary artery disease * •Enlarged heavy heart, hypertrophied, dilated LV * •Atherosclerosis – usually all of the cause * •Maybe mural thrombi * •Fibrosis (microscopic)

Answer 31

* “Unexpected death from cardiac causes in individuals without symptomatic heart disease or early (1hr) after onset of symptoms” * Usually due to lethal arrhythmia * Usually on background of IHD (90%) * 300,000 - 400,000 per annum in USA * Acute myocardial ischaemia is usual trigger * Usually causes electrical instability at sites distant from conduction system often near scars from old MIs * Other conditions also associated eg Aortic stenosis (can lead to sudden death), mitral valve prolapse, pulmonary hypertension * Marked atherosclerosis (\>75% stenosis) in one or more vessels usually \>90% * 10% non atherosclerotic cause-\> (long QT etc) usually young, fit people with a strong FHx * ½ have plaque rupture. * 25% have MI changes but conflicting data on role of MI * Felt to be ischaemia induced electrical instability * Some cases heritable

Answer 32

* End point of many conditions * Congestive Heart Failure (L&R) * Left sided (-\> SOB, pulmonary oedema) * Right sided (-\> peripheral oedema) * Causes * –Ischaemic heart disease * –Valve disease * –Hypertension * –Myocarditis * –Cardiomyopathy * – Left sided heart failure (Right) Complications * Sudden Death – due to arrhythmia * Arrhythmias * Systemic emboli – due to inappropriate pumping * Pulmonary oedema with superimposed infection Pathology: * •Dilated heart, Scarring & thinning of the walls * •Microscopy: fibrosis and replacement of ventricular myocardium

Answer 33

Too thin – dilated, * •Progressive loss of myocytes * •Dilated heart * •Causes: * –Idiopathic * –Infective – viral myocarditis * –Toxic: alcohol, chemotherapy (adriamycin, daunorubicin), cobalt, iron * –Hormonal – hyper-, hypo- thyroid, diabetes, peri-partum (?) * –Genetic – haemochromatosis, Fabry’s, McArdle’s * –Immunological – myocarditis incl. Viral (hypersensitivity component) too thick – hypertrophic and it doesn’t work properly, * •Left ventricular hypertrophy * •Familial in 50% (autosomal dominant, variable penetrance) * •Beta-myosin heavy chain * •Thickening of septum narrows left ventricular outflow tract * •Sudden death too stiff – restrictive caused by amyloid etc * •Impaired ventricular compliance * •Idiopathic or secondary to myocardial disease eg amyloid, sarcoidosis * •Normal size heart – big atria

Answer 34

Chronic rheumatic valvular disease: * •Sequelae of earlier rheumatic fever * •Predominantly left-sided valves (almost always mitral) * –Mitral \> Aortic \> Tricuspid \> Pulmonic * –Mitral alone 48%, Mitral + aortic 42% * •Thickening of valve leaflet, especially along lines of closure * •Fusion of commissures * •Thickening, shortening and fusion of chordae tendineae Calcific aortic stenosis * •Commonest cause aortic stenosis * •70s or 80s * •Calcium deposits outflow side cusp * •Impairs opening * •Orifice compromised * •Outflow tract obstruction Aortic regurgitation * •Causes * –Rigidity - rheumatic, degenerative * –Destruction - microbial endocarditis * –Disease of aortic valve ring * =\> dilatation =\>valve insufficient to cover increased area * •Marfan's Syndrome * •Dissecting aneurysm * •Syphilitic aortitis * •Ankylosing spondylitis Endocarditis * If you have a damaged valve then you’re more likely to have endocarditis, esp if you have had a valve replaced; IV drug users get RHS endocarditis – inject into their veins so goes first to the Tricuspid valve * Normal endocarditis get LHS usually

Answer 35

* True aneurysm - all layers wall * False aneurysm – extravascular haematoma * Causes: Weakness of the artery wall * –Congenital eg Marfans * –Atherosclerosis * –Hypertension Atherosclerosis may weaken the wall of the aorta such that it bulges out to form an aneurysm. An atherosclerotic aortic aneurysm typically occurs in the abdominal portion below the renal arteries, as shown here. Aortic aneurysms that get bigger than 6 or 7 cm are likely to rupture. A dissection – forms a false lumen, which can cause problems – in coronary artery can get ischaemia distally and are prone to rupture * AAA – tend to rupture * Aortic arch aneurysms tend to dissect, and then rupture

Answer 36

* Do an examination of the body first: * o Hands – clubbing, scars, splinter haemorrhages * o Scar from median sternotomy – measure it and document (indicates CABG) * o Look at the legs for vein harvest scar – measure and document * o Hip replacement * o Any operations on neck, any cyanosis on face * • Check name tag and identification of patient * • Make an incision from Adams apple to pubis to examine organs * o Everyone has some subcutaneous fat * o Patient has a lot of ascites (liver and cardiac failure) * o Must remove chest plate on top of heart and lungs * • Cut through ribs * o Pericardium adheres to chest plate * o Can see wires from CABG * o Blood stained pleural effusions * • Cut through trachea and great vessels in neck * o Remove heart and lungs in one block * o Detach back of aorta * • Detach large intestine * o Pathology to see: * Cancers * Perforation: faecal material, bad smell * Ischaemic bowel * Diverticular disease: balloons of mucosa coming out * Strictures * Perforation * • Take out liver, spleen, pancreas, small bowel in another block * • Kidneys, bladder, ureters, prostate come out * o Also look at vessels for ruptured aneurysms * • Genitals * o Hernia * • Organs go back in body in plastic bag * • All sown up with suture material and can be buried and cremated * • Can take swabs or samples of collections to the lab * • Deposits of tumour on peritoneum, chest, ribs

Answer 37

* Anything obvious: tumours, infection * • Aorta has artefactual clot due to preservation process * • Separate right lung * • Operations or myocarditis means pericardium is very adherent to surface of the heart * o This makes a re-do CABG very hard * • Pericardial space is what fills with tamponade * • Grafts prone to atheroma and blockage * o Healthy graft so not cause of death in this patient * • Very big heart * • LV Fibrosis – MI, ischaemia * o Haemorrhagic * o Dilated (hypertensive heart disease) * o Initially thickens to work harder but then dilates * o 550g – normal man’s heart should be 350g * o cut across to look for scars or infarction * • Valves * o Look for endocarditis * o Prosthetic valves * • Aorta

Answer 38

* Obvious tumours * • Lymph nodes (cancer will go here – breast, colon, liver, brain) * • Section through the lung * o Infection – pneumonia, abscess * o Pneumonia – lung that isn’t black (normal lung goes black on fixation) * o Tumour * Lots of small deposits: secondary * One mass: primary * Pulmonary oedema (everyone has this eventually if they die suddenly) * o Fibrosis * o Mesothelioma – thickened pleura * o PE * o Military TB – pockets of infection/white specks (small abscesses)1

Answer 39

* Small bowel infarction * • Large bowel cancers * • Appendix * • Ischaemic bowel is black and necrotic * • Diverticular disease * o Fibrosis * o Perforation * o Gets stuck to bladder/vagina -\> fistula (communication) * o Very hard to operate on * o Cause: low fibre diet * • Crohn’s * o Skip lesions * o Mouth to anus * • UC * o Starts at anus * o Lower down * • Stomach * o Cancers * o Ulcers * o Varices occur at GOJ * o H.pylori – from stomach (pyloric sphincter area) to duodenum is where ulcers occur * • Pancreas * o Chronic/acute pancreatitis – gallstones and alcohol * o Pancreatic cancer * o Diabetes * • Liver * o Metastases – dual blood supply * o Tumours * o Infection * o Cirrhosis * o Fatty change * • Fractured NOF * o Falls due to osteoporosis * o Can also be caused by prostate/breast cancer * o These older people do not do well after NOF operations * Likely to get PE

Answer 40

* Look at fat for lymph nodes * • Lymphoma causes large nodes * o Infection * o Bowel spread * • Wedge shaped white spaces = infarcted kidney * • Stones in collecting duct * • Tumours of transitional epithelium * • Look at strip surface – HTN causes scarring/pits * • Thinning cortex of kidney with HTN * • Common cystic change in kidney * • Uterine and ovary cancer present late – very bad prognosis * o Bloating * o Bleeding * • Fallopian tube – ruptured * o Ectopic pregnancies * • Testes tumour * o Common in younger men 20-30s – teratoma * o Torsion: * Bell clapper deformity * Horse riding * Presents early – big swollen

Answer 41

* Meninges * o Stripped * o 3 types of haemorrhage: * Extradural * Subdural * SAH * • Berry aneurysm * • Strokes * o Haemorrhagic * o Ischaemic * o Always think cocaine in younger people * • Brain tumour * Most common: metastases * Usually multiple, can be single * From: breast, lung, gut, melanoma (pigmented) * Primary brain tumours never metastasize outside the brain * Position of tumour is important * Benign tumour in bad place causes mortality * Malignant tumour in not bad place – less problems

Answer 42

* Divided into 2 sections: * Section 1a, b, c – deals with cause of death * A: immediate * B: led to A * C: led to B * Section 2 * Contributory factor * Did not directly cause death * Example * 1a) MI * 1b) coronary artery atheroma * 2) Diabetes, hypertension * You cannot give a mode of death as a cause of death. Heart failure is not an immediate cause of death. * 1a) hypertensive and ischaemic heart disease * 1b) hypertension and coronary atheroma * You can have more than one immediate cause

Answer 43

* Mode * Cardiac failure * Respiratory failure * Renal failure * Not a mode * 1a) Ischemic heart disease * 1b) Hypertensive heart disease * 1a) Type 1 respiratory failure * 1b) Pulmonary embolism, LRTI * 1a) Type 2 respiratory failure * 1b) Asthma, drugs * OR just avoid the term respiratory failure and list the cause e.g. PE * 1a) SLE, diabetes, infection Examples: 1. 86 y/o female, PMH: T2DM, dementia. Fell down stairs, fractured NOF. Treated surgically. Collapsed on ward 24h later. * 1a) Pulmonary embolism * 1b) DVT * 1c) Fractured neck of femur 2. 76 y/o male, PMH: T1DM, ankylosing spondylitis. Collapses at home, Stroke * 1a) ischaemic stroke * 1b) embolism * 1c) arrhythmia 3. 63y/o male. Boiler maintenance worker and Lifelong smoker. Cough for 2 years. Massive haemoptysis. * 1a) haemorrhage * 1b) lung cancer * 2) smoking and asbestos exposure (multiplicative effect with smoking) 4. 78 y/o female. SLE, Sudden left sided weakness, paralysis, poor swallow. Progressively deteriorates and tachypnoea and dies. * 1a) aspiration pneumonia * 1b) stroke * 2) SLE

Histopathology Flashcards

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