Histopathology

Question 1

What are the major functions of the kidney?

Answer 1

• •Excretion of metabolic waste products and foreign chemicals (including drugs)
• •Regulation of fluid, electrolyte and acid/base balance
• •Regulation of blood pressure
  
  • •Renin
• •Regulation of calcium and bone metabolism
  
  • •1,25 Dihydroxycholecalciferol
• •Regulation of haematocrit
  
  • •Erythropoietin

Question 2

What is the anatomical position of the kidney?

Answer 2

• •Retroperitoneal
• •T12 to L3 on left; right is lower
• •Mean length 11cm
• •Normal weight 125-170g (male), 115-155g (female)
• •Receive around 20% of cardiac output
• •Basic unit is the nephron:
  
  • •Glomerulus
  • •Afferent and efferent arterioles
  • •Tubules
• •Approximately one million nephrons per kidney
• •Large functional reserve

Question 3

What is the function of the nephron?

Answer 3

• •Blood is filtered at the glomerulus
  
  • •High hydrostatic pressure (60mmHg)
  • •Podocytes create charge-dependent (anionic) and size-dependent barrier
  • •125 mL/min
• •The filtrate is modified in the tubules
  
  • •Proximal convoluted tubule
    
    • •actively resorbs sodium
    • •Hydrogen exchange to allow carbonate resorption
    • •Co-transport of amino acids, phosphate, glucose
    • •Potassium is also reabsorbed
  • •Loop of Henle
    
    • •doubles back on itself
    • •Descending / thin ascending limb permeable to water but not ions or urea; ascending limb actively resorbs sodium and chloride
    • •Countercurrent Multiplier; aligned with vasa recta
  • •Distal convoluted tubule
    
    • •is impermeable to water
    • •Regulates pH via active transport (proton / bicarbonate)
    • •Regulates sodium, potassium via active transport (aldosterone)
    • •Regulates calcium (parathyroid hormone, 1,25 dihydroxycholecalciferol
  • •Collecting tubule
  • •Collecting Duct
    
    • •Resorbs water (principal cells, antidiuretic hormone)
    • •Regulates pH (intercalated cells, proton excretion)

Question 4

What is the histology of each part of the kidney?

Answer 4

Cortex:

• crowded and lots of tubules – very little wasted space; very metabolic tissue

Glomerulus:

• Filtration is collected, with afferent arteriole and efferent arteriole; mesangion in between; capillary loops;
• podocytes present in the glomerulus with their foot processes present with the basement membranes
• The endothelial cells are fenestrated, with gaps shown

Question 5

Where do immune complexes deposit in the kidney?

Answer 5

• •Latticework of antibody and antigen
  
  • •May be endogenous or exogenous antigens
• •May deposit in the glomerulus
  
  • •Inflammatory response
  • •Complement activation
  • •Stimulation of inflammatory cells
• •May deposit at different rates
• •May deposits at different sites
• •Endothelium with basement membrane – podocytes can’t be seen as they have been injured inflammation; igg and c3 with nephrotic syndrome = membranous glomerulonephritis

Question 6

What are the symptoms of renal disease?

Answer 6

• Haematuria
• Proteinuria
• Uraemia
• Hypertension
• Oliguria / Anuria
• Polyuria
• Oedema – lots of protein lost in urine, which provide oncotic pressure
• Colic

Question 7

How do we classify renal disease?

Answer 7

•Syndromes

• •Acute renal failure, nephrotic syndrome, microscopic haematuria

•Morphological Changes

• •Glomerulonephritis, thrombotic microangiopathy, focal-segmental glomerulonephritis

•Aetiology

• •Congenital, Systemic Lupus Erythematosus, amyloidosis, drugs, infections

Question 8

What are some examples of genitourinary malformations?

Answer 8

• Agenesis
• Renal Fusion (e.g. horse-shoe)
• Ectopic Kidney
• Renal Dysplasia – not properly formed
• Pelvi-ureteric Junction Obstruction
• Ureteral Duplication
• Vesicoureteral Reflux
• Posterior urethral Valves

Question 9

What are some cystic diseases of the kidney?

Answer 9

• •Adult (Dominant) Polycystic Kidney Disease
  
  • •1:500
  • •10% of end-stage renal failure
  • •Presents in adulthood with hypertension, flank pain and haematuria
  • •PKD1, PKD2…
  • •Berry aneurysm…
• •Cysts commonly develop in patients with end stage renal disease who are on dialysis
  
  • •Multiple
  • •Bilateral
  • •Cortical and Medullary
• •Increased risk of development of malignancy
  
  • •7% risk at 10 years
  • •Papillary renal cell carcinoma most common; clear cell carcinoma can also arise

Question 10

What are some examples of medical renal disease syndromes?

Answer 10

•Acute Renal Failure (Acute Kidney Injury) – 1 mainly presents

• •Rapid deterioration in renal function (hours, days)
• •Common, often in the setting of pre-existing disease
• •Causes include
  
  • •Pre-Renal: Failure of perfusion
  • •Renal: Acute tubular injury, acute glomerulonephritis, thrombotic microangiopathy
  • •Post-Renal: Obstruction (tumour in prostate/bladder)
• •Presentation and prognosis variable
• Nephrotic Syndrome – 3 tend to present in this way
• Isolated Urinary Abnormalities
• Chronic Kidney Disease

Question 11

What is acute tubular injury?

Answer 11

• Commonest cause of acute renal failure
• Tubular epithelial cells damaged by
• •Ischaemia
• •Toxins (contrast in radiology, haemoglobin, myoglobin in rhabdomyolysis, ethylene glycol)
• •Drugs
• Common in critical illness
• Drugs that inhibit vasodilatory prostaglandins predispose
• •NSAIDs

Pathogenesis

• Normal tubule with integrin which anchors the cell and intact brush border; 1st sign is loss of Na/K atpase and loss of brush border;
• then shedding of epithelial cells;
• then spreading of the cells which are left and hopefully at the end there is resolution due to surviving cells prolif and diff to take up the place of those that were harmed

•Failure of Glomerular Filtration

• •Blockage of tubules by casts
• •Leakage of tubules to interstitial space – can cause further injury
• •Secondary haemodynamic changes – which can affect the kidneys too

Question 12

What is acute tubulo-interstitial nephritis?

Answer 12

• Immune injury to tubules and interstitium
• Can also be due to infection and drugs
• •NSAIDs
• •Antibiotics
• •Diuretics
• •Allopurinol
• •Proton Pump Inhibitors – usage increasing

•Heavy interstitial inflammatory infiltrate with tubular injury

• •Can see eosinophils, granulomas, lymphocytes overcoming the tubule

Question 13

What is acute glomerulonephritis?

Answer 13

• Acute inflammation of glomeruli
• Presents with oliguria with urine casts containing erythrocytes and leucocytes
• When sufficient to cause acute renal failure, there are almost always crescents
• •Proliferation of cells within Bowman’s space

•Image with silver stain = ex-capillary perforation and cresence meaning substances of nephron pushed to the side, focal segmental glomerulonephritis with cresence

Question 14

What is acute crescentic glomerulonephritis?

Answer 14

• Immune Complex
• Anti Glomerular Basement Membrane Disease
• Pauci-immune (anti-neutrophil cytoplasm antibodies)
• Leads rapidly to irreversible renal failure
• Correct diagnosis and treatment are urgent

Question 15

What is immune complex associated crescentic glomerulonephritis?

Answer 15

• Aetiologies include SLE, IgA nephropathy and Post-Infectious Glomerulonephritis
• Immune complexes can be identified and localised with immunohistochemistry and electron microscopy
• Final diagnosis depends on specific findings interpreted within the appropriate clinical context.

Question 16

What is anti-GBM disease?

Answer 16

•Rare and severe disease caused by antibodies directed against the glomerular basement membrane

• •C-terminal domain of Type IV collagen
• •May cross-react with alveolar basement membrane leading to pulmonary haemorrhage
• •Antibody may be detected with serology
• Linear deposition of IgG demonstrable on glomerular basement membrane
• Linear green of IgG and the rest has been taken up by the cresence

Question 17

What is pauci-immune crescentic glomerulonephritis?

Answer 17

• Only scanty glomerular immunoglobulin deposits
• Usually ANCA-associated
• Trigger neutrophil activation and glomerular necrosis
• Vasculitis elsewhere

Question 18

What is thrombotic microangiopathy?

Answer 18

• Damage to endothelium in glomeruli, arterioles, arteries leading to thrombosis
• When thrombus is formed, you can undergo haemolytic anaemia because the RBC are being shred, as they can’t pass through the different strands
• Red cells may be damaged by fibrin
• •Microangiopathic haemolytic anaemia
• •Haemolytic Uremic Syndrome

•Diarrhoea associated

• •Bacterial gut infection such as with E. coli
• •Toxins released that target renal endothelium

•Non-Diarrhoea associated

• •Defects in regulation of complement
• •Deficiency in ADAMTS13
• •Drugs (calcineurin inhibitors)
• •Radiation
• •Hypertension
• •Scleroderma
• •Antiphospholipid Antibody Syndrome (+/- SLE)

Question 19

What is nephrotic syndrome and its causes?

Answer 19

•Breakdown in selectivity of glomerular filtration barrier leading to protein leak

Signs:

• •Proteinuria (>3.5g/day)
• •Hypoalbuminemia
• •Oedema
• •Hyperlipidaemia
• •At risk of dvt and pe due to altering the contents of the blood

Causes:

• •Primary Glomerular Disease, Non-Immune Complex Related
  
  • •Minimal Change Disease
    
    • •Glomeruli look normal by light microscopy
    • •Effacement of foot processes on electron microscopy – looks like a smudge on the slide/basement membrane
    • •Common cause of nephrotic syndrome in children
    • •Generally responds to immunosuppression
  • •Focal Segmental Glomerulosclerosis
    
    • •Some (focal) glomeruli are partially (segmental) scarred
    • •Less likely to respond to immunosuppression
    • •Must exclude possible other diseases that can produce a similar appearance
      
      • •These tend not to be nephrotic
      • •Only if all the syx fit this then we move from the pathology to the disease but need to exclude other diseases first
• • •Primary Renal Disease, Immune Complex Mediated
    * •Membranous Glomerulonephritis
    * •Associated with immune deposits on outside of glomerular basement membrane
    * •Subepithelial
    * •Common cause of nephrotic syndrome in adults
    * •Primary disease is autoimmune
    * •Antibody against phospholipase A2 type M receptor (PLA2R) in 75% of cases
    * •Need to exclude possibility of a secondary disease
    * •Epithelial malignancy, drugs, infections, SLE
    * •Interpret findings in clinical and serological context
• • •Systemic Disease
    * •Diabetes mellitus
    * •Amyloidosis
    * •SLE

Question 20

What is diabetic nephropathy?

Answer 20

• 30-40% of diabetics
• High glucose levels thought to be directly injurious
• Typically starts as microalbuminuria before progression to proteinuria and nephrotic syndrome
• Nodular Glomerulosclerosis
• •Stage 1 – Thickening of basement membrane on EM
• •Stage 2 – Increase in mesangial matrix, without nodules
• •Stage 3 – Nodular lesions / Kimmelstiel-Wilson not specific but very suggestive
• •Stage 4 – Advanced glomerulosclerosis

Question 21

What is amyloidosis?

Answer 21

• Deposition of extracellular proteinaceous material exhibiting β-sheet structure
• Congo red stain – apple green birefringence
• Commonest forms in kidney are
• •AA, derived from serum amyloid associated protein (SAA), an acute phase protein; patients tend to have a chronic inflammatory state
• •AL, derived from immunoglobin light chains; 80% of patients have multiple myeloma

Question 22

What are some examples of isolated urinary abnormalities?

Answer 22

•Microscopic Haematuria

• •Thin basement membranes
• •IgA Nephropathy

•Asymptomatic Proteinuria

• •May be associated with a broad range of glomerular structural abnormalities or immune complex deposition
• •Diagnosis often requires renal biopsy for histology, immunohistochemistry and electron microscopy

Thin basement membranes:

• •Hereditary defect in Type IV collagen synthesis
• •Basement membrane <250nm thickness
• •Haematuria is only consequence in most cases

•Alport’s Syndrome

• •X-linked dominant mutations affecting ⍺5 subunit
• •Forms exist in which mutation affects ⍺3 or ⍺4 subunit
• •Typically progressive, renal failure in middle age
• •Often have deafness, ocular disease
• •Very thin basement membrane present

Question 23

What is IgA nephropathy?

Answer 23

• Commonest glomerulonephritis
• IgA predominant mesangial immune complex deposition
• Aetiology not well understood in primary form
• •Secondary forms observed in liver, bowel and skin disease
• •Can be seen with small-vessel vasculitis (Henoch-Schönlein Purpura)
• 30% develop end stage renal failure
• Oxford Classification (MEST-C; mesangial hypercellularity, endocapillary hypercellularity, segmental scarring, tubulointerstitial fibrosis, crescent formation)

Question 24

What is chronic kidney disease?

Answer 24

• Can be caused by a large number of diseases
• Significant cause of morbidity and mortality
• Association with ischaemic heart disease
• •Hypertension, hyperlipidaemia, calcification of blood vessels

•Association with calcium and phosphate metabolic derangement

• •Hyperparathyroidism, osteomalacia, osteoporosis

•UK Renal Registry 19th Annual Report lists causes of chronic renal failure requiring renal replacement therapy by prevalence:

• •Diabetes – 27.5%
• •Glomerulonephritis – 14.1%
• •Polycystic Kidney Disease – 7.4%
• •Pyelonephritis – 6.5%
• •Hypertension – 6.8%
• •Renal Vascular Disease – 5.9%
• •Other / Uncertain – 31.7%

Question 25

What is hypertensive nephropathy?

Answer 25

•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

Question 26

How does SLE affect the kidneys?

Answer 26

• 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

Question 27

What are urinary calculi?

Answer 27

•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

Question 28

What are the different types of bening kidney tumours?

Answer 28

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

Question 29

What are the different types of malignant renal neoplasms?

Answer 29

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

Question 30

What are the different types of urothelial carcinomas?

Answer 30

• •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

Question 31

What is benign prostatic hyperplasia?

Answer 31

• •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 ​

Question 32

What are prostatic adenocarcinomas?

Answer 32

• •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

Question 33

What are the different types of testicular germ cell tumours?

Answer 33

• •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

Question 34

What are testicular non-germ cell tumours?

Answer 34

• •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

Question 35

What are paratesticular diseases?

Answer 35

• •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

Question 36

What are the different penile diseases?

Answer 36

• •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

Question 37

What are the different urethral diseases?

Answer 37

• •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

Question 38

What are the different scrotal diseases?

Answer 38

• •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

Question 39

What are the symptoms of HIV?

Answer 39

•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

Question 40

What is the pathology of mycobacterium?

Answer 40

• 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

Question 41

What is sarcoid?

Answer 41

• 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

Question 42

What is the pathology of IgG related diseases?

Answer 42

• 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

Question 43

Which diseases are caused by alcohol?

Answer 43

• •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

Question 44

What effect do fizzy drinks have on the body?

Answer 44

Question 45

What is the effect of cystic fibrosis on the body?

Answer 45

• 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

Question 46

What is the effect of amyloid?

Answer 46

• 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

Question 47

What is atherosclerosis?

Answer 47

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

Question 48

What are vulnerable plaques made from?

Answer 48

• •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

Question 49

What are the consequences of an atheroma?

Answer 49

•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

Question 50

How does vasoconstriction occur?

Answer 50

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

Question 51

What is IHD?

Answer 51

• •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

Question 52

What are acute coronary syndromes?

Answer 52

•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

Question 53

What is reperfusion injury?

Answer 53

• 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

Question 54

What are the complications of MI?

Answer 54

• •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

Question 55

What is chronic IHD?

Answer 55

• •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)

Question 56

What is sudden cardiac death?

Answer 56

• “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

Question 57

What is cardiac failure?

Answer 57

• 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

Question 58

What is cardiomyopathy?

Answer 58

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

Question 59

What is cardiac valve disease?

Answer 59

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

Question 60

What are aneurysms?

Answer 60

• 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

Question 61

What are the steps of inspection and evisceration in a post-mortem?

Answer 61

• 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

Question 62

What are we looking for in a postmortem of the heart?

Answer 62

• 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

Question 63

What are we looking for in a postmortem of the lungs?

Answer 63

• 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

Question 64

What are we looking for in a postmortem of the abdomen?

Answer 64

• 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

Question 65

What are we looking for in a postmortem of the genitourinary system?

Answer 65

• 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

Question 66

What are we looking for in a postmortem of the brain?

Answer 66

• 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

Question 67

How do we medically certify cause of death?

Answer 67

• 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

Question 68

What are examples of mode of death and examples of certifcation?

Answer 68

• 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