Past exam of the medicine course of the University of Oxford / 1864 / Second examination / Pathology. medical, surgical (No. I.)

Original volume: Examination papers for the Degree of Bachelor of Medicine by the University of Oxford (1864–1867). Open the original paper in the scanned volume. PDF pages 15–15; Oxford, December 2, 1864.

Historical names are retained where necessary, with present explanations distinguished from what those names established in 1864. These are educational descriptions of disease and diagnosis.

Original questions are transcribed from the public-domain edition. Credit: Wellcome Collection; original supplied by Royal College of Physicians, London. Source and public-domain rights statement.

Describe the microscopical appearances of typical specimens of encephaloid Carcinoma, and Fibro-plastic growth.

The typical contrast is between a highly cellular, relatively scantily supported encephaloid cancer and a fibroplastic growth composed predominantly of elongated cells and developing fibrous material. Neither historical name is a complete modern tumour classification.

In encephaloid cancer, a thin preparation from a viable region shows crowded, variably sized cells, often rounded, oval, polygonal or irregular, with conspicuous cell nuclei and a prominent cell nucleolus. Some cells have more than one cell nucleus; the cytoplasm and nuclear proportions vary. In sections, the cells form masses or groups separated by a comparatively delicate vascular stroma. Where the lesion is a carcinoma, cohesive epithelial arrangements and invasion of surrounding tissue help establish its nature. The scant support helps explain the soft, brain-like gross consistency denoted by “encephaloid”; it does not mean that the growth is made of brain tissue.

A rapidly growing soft tumour may also show evidence of mitosis, haemorrhage, necrosis and granular or fatty cellular debris. These features vary with sampling and are not the definition of every historical encephaloid lesion. The viable advancing edge is more informative about cell type and invasion than a completely broken-down centre. A modern interpretation combines architecture, cell morphology and, where needed, immunohistochemistry; one large nucleolated cell is not a universal “cancer corpuscle.”^[ref][ref]

In a typical fibroplastic growth, the conspicuous elements are oval or spindle-shaped cells, with elongated cell nuclei, tapering processes and intercellular material taking on a fibrillar character. The cells may run in parallel bundles or interlacing groups. Some areas contain many apparently free oval cell nuclei; other areas show more mature fibres and fewer obvious cell bodies. A teased preparation helps display individual elongated cells and fibres, whereas a section shows how the bundles relate to vessels and surrounding tissue.

The historical interpretation was of a growth resembling developing connective tissue. It should not be translated automatically into either a harmless fibroma or a specific modern fibrosarcoma. Contemporary descriptions recorded recurrence and malignant behaviour in some growths put in this broad category.^[ref] Cell shape must be read with tissue architecture and behaviour. Apparent resemblance to fibroblasts does not establish benignity, and a scant-fibred soft growth is not by itself proof of epithelial origin.

Describe the condition called Leucocythemia.

Leucocythaemia was the historical description of a persistent excess of white corpuscles in the blood, commonly accompanied by enlargement of blood-forming or lymphoid organs. The corresponding modern disease group is leukaemia, but a raised leukocyte count alone is not a sufficient modern diagnosis.

A period investigation would compare the proportions and appearances of the white and red corpuscles in a fresh blood preparation and examine the spleen, lymph nodes and liver. Splenic enlargement could be striking, and enlarged lymphatic glands supplied another important pattern. The white material was not simply pus circulating from an unnoticed abscess; microscopic resemblance between a leukocyte and a pus corpuscle does not establish suppuration. A persistent excess must also be distinguished from a temporary reactive rise during infection or inflammation.

In present terms, leukaemia comprises malignant disorders of blood-forming cells. Acute and chronic forms, and myeloid and lymphoid lineages, differ in the maturity and identity of their abnormal cells and in their course. Bone marrow disease can interfere with normal production of red blood cells, platelets and functioning leukocytes. Thus pallor, fatigue and breathlessness may reflect anaemia; bruising or bleeding may reflect inadequate platelets; recurrent infection can occur despite a large total white count. Infiltration or enlargement of the spleen, lymph nodes and liver can produce swelling, early satiety or abdominal discomfort.^[ref]

The useful modern examination includes a complete blood count and differential, a stained blood film, and investigation of bone marrow and cellular markers when indicated. The morphology and proportions of mature and immature cells matter. A count can be normal or low in some leukaemias, while a high count can have a non-malignant cause.^[ref] The historical appearance suggests a disorder of blood formation, but classification requires more than counting white cells.

Distinguish between what are termed Typhus and Typhoid Fever.

Typhus and typhoid fever are distinct infections, despite their overlapping fever, prostration and delirium. In the British historical comparison, typhus chiefly means epidemic louse-borne typhus, not every disease now called a typhus fever.

Classical typhus often begins relatively abruptly with severe headache, fever, prostration and a conspicuously ill mental state. Its eruption is commonly a more extensive dusky maculopapular rash on the anatomical trunk and limbs and may become petechial. Crowded conditions and infestation with body lice support the epidemiological distinction. Modern knowledge identifies Rickettsia prowazekii and transmission involving infected louse material. Injury to small-vessel endothelium helps explain the widespread illness; it is not chiefly a local ulcerating disease of the ileal lymphoid tissue.^[ref]

Typhoid fever more often develops insidiously, with persistent fever, headache and progressive weakness, together with abdominal discomfort, distension and either constipation or diarrhoea. Sparse, transient rose spots may occur on the anatomical trunk. Splenic enlargement and intestinal complications are important. The characteristic pathological process involves intestinal lymphoid tissue, especially Peyer's patches in the terminal ileum, with enlargement, necrosis and ulceration. Severe ulcers can bleed or perforate.^[ref]

Modern causation separates typhoid fever, due to Salmonella Typhi, from louse-borne typhus. Typhoid fever spreads through food or water contaminated by human excreta, including material from carriers; it is not acquired merely because an air space is crowded. A prolonged course, abdominal findings and intestinal haemorrhage favour it, whereas abrupt severe illness with a widespread dusky rash and louse exposure favour typhus.^[ref]

Neither the rash nor the bowel habit is invariable, and the old contrast between an approximately two-week typhus and a longer enteric illness is a tendency, not a diagnostic clock. An absent rose spot does not exclude typhoid fever, and an absent rash does not exclude typhus. Modern confirmation uses organism-appropriate investigations, including blood culture for enteric fever and appropriate serological or molecular testing for typhus. The important historical achievement is the separation of the syndromes; the later microbiological explanation should not be projected into every 1864 diagnostic account.

What causes may produce general Anasarca ?

General anasarca is extensive interstitial fluid accumulation, produced when vascular filtration exceeds the capacity of lymphatic drainage and the body's regulation of salt and water. Several mechanisms commonly act together.

Raised venous and capillary hydrostatic pressure promotes filtration. Heart failure, especially when systemic venous pressure is elevated, is a major example; renal retention of sodium and water reinforces the swelling. Severe kidney failure can itself cause general fluid overload when salt and water cannot be excreted adequately. Acute glomerulonephritis may therefore cause widespread oedema without requiring the extremely low plasma protein concentration of every nephrotic case.^[ref]

Reduced plasma oncotic pressure contributes when circulating albumin is markedly depleted. Causes include heavy urinary protein loss in nephrotic syndrome, reduced synthesis in advanced liver disease, protein loss through the intestine, and severe malnutrition. In cirrhosis, altered circulation and renal salt retention add to reduced protein synthesis; the mechanism cannot be reduced to a single blocked vein. Likewise, nephrotic syndrome can include primary renal salt retention as well as a fall in oncotic pressure.^[ref]

Increased vascular permeability during severe systemic inflammation, sepsis or extensive tissue injury can allow fluid and protein into the interstitium. Impaired lymphatic drainage can amplify systemic oedema, although a single obstructed lymphatic or vein ordinarily causes regional rather than general swelling. Excess administered fluid and some drugs can contribute by salt retention or altered vascular tone. Multiple mechanisms are particularly likely in a severely ill patient.

A nineteenth-century description would group much of this as cardiac, renal or hepatic “dropsy,” and might invoke an impoverished state of the blood. Modern physiology specifies the abnormalities that those broad descriptions leave unresolved. A general examination should distinguish pitting fluid accumulation from a predominantly non-pitting disorder such as myxoedema, and from isolated ascites. The distribution, jugular venous filling, heart and lung findings, urinary albumin, renal function and plasma albumin help distinguish causes. Anasarca is a sign with several possible causes, not a diagnosis of renal disease by itself.

Under what several conditions is the Urine found to contain (1) Albumen, (2) Sugar, and (3) Pus globules ?

Urinary albumin, glucose and leukocytes represent different abnormalities, and none alone identifies one disease. A fresh, appropriately collected specimen and confirmation of the constituent are essential before interpreting it.

Persistent albuminuria commonly reflects increased passage of albumin across an injured glomerular filtration barrier. Examples include glomerulonephritis, diabetic kidney disease and other protein-losing glomerular disorders. Renal vascular congestion and severe systemic illness can also increase excretion. Transient albuminuria can accompany fever, strenuous exercise or a urinary tract infection; an upright-posture-related pattern may disappear in an early-morning specimen. Blood or inflammatory material added downstream can contribute protein, so a protein-positive specimen need not mean that every protein molecule crossed a diseased glomerulus.^[ref]

Albuminuria should be distinguished from the broader term proteinuria. Reduced tubular recovery and overproduction of other small proteins can produce different urinary protein patterns. A modern urine albumin-to-creatinine measurement helps quantify albumin loss and reduce the effect of variable dilution.^[ref] The historical “albumen” category does not imply that every old heat or precipitation test was chemically specific for albumin.

Glycosuria results either from an excessive filtered glucose load or reduced renal recovery. Diabetes with hyperglycaemia is the major systemic example. Transient hyperglycaemic states may also cause it; renal glycosuria, pregnancy-related changes and proximal tubular dysfunction can produce glycosuria without sustained diabetic hyperglycaemia. Modern drugs that deliberately reduce renal glucose recovery provide another mechanism, but should not be attributed to 1864 practice.^{[ref] [ref]} Urinary sugar is therefore a reason to examine blood glucose, not proof of one diabetes subtype. Historical reducing-sugar reactions also require care because chemical reduction is not uniquely specific to glucose.

“Pus globules” correspond chiefly to leukocytes, especially neutrophils. Pyuria occurs with cystitis, pyelonephritis, urethral or prostatic infection and suppuration draining into the urinary tract. It can also occur with stones, urinary tuberculosis, interstitial nephritis and other inflammatory disorders, or through contamination by genital secretions. Previous antimicrobial treatment or organisms not recovered by a routine culture can leave apparently sterile pyuria.^[ref][ref]

A wet sediment examined with a microscope can show leukocytes, red blood cells and urinary casts; urine culture addresses a different question about detectable organisms. White-cell casts suggest inflammation within the kidney rather than simply pus added in the bladder, but are not unique to bacterial pyelonephritis. “Pus in urine” neither localises every lesion nor proves an ordinary bacterial infection.

By what conditions is Jaundice produced; and in which may it be considered remediable either by nature or by art ?

Jaundice results from accumulation of bilirubin; its reversibility depends on the cause, not on the yellow colour alone. In 1864, obstruction of bile flow and disease of the liver were important practical distinctions. Modern physiology also separates excess production from impaired uptake, conjugation and excretion.

Excess breakdown of red blood cells can overwhelm the usual handling of bilirubin, producing predominantly unconjugated hyperbilirubinaemia. Impaired hepatic uptake or conjugation supplies another non-obstructive mechanism. Hepatocellular injury, as in hepatitis or advanced cirrhosis, impairs processing and secretion. Intrahepatic cholestasis and extrahepatic obstruction prevent normal disposal through bile. Obstruction can result from a gallstone, a duct stricture, inflammation or compression/invasion by a tumour.^[ref]

Conjugated bilirubin can enter the urine, making it dark; predominantly unconjugated bilirubin, which is strongly protein-bound, does not ordinarily produce bilirubinuria. Marked interruption of bile delivery can make stools pale. These findings help locate the problem but do not by themselves distinguish a stone from a stricture or cancer. Modern fractionated bilirubin tests, liver enzymes and ultrasonography supplement the clinical pattern.^[ref]

Recovery “by nature” is possible when an obstruction is temporary, a small gallstone passes, a reversible inflammatory process settles, or the cause of increased pigment production ceases. An episode of jaundice can clear as liver function recovers. It is nevertheless unsafe to infer a harmless or self-limiting cause merely because the jaundice fluctuates; partial malignant obstruction can also fluctuate.

Recovery “by art,” in modern terms, includes treating a reversible underlying illness and relieving a remediable obstruction. A persistent common-duct stone can be removed endoscopically or surgically; an obstructed duct may require drainage. Selected strictures and tumours can be treated, but established extensive hepatic destruction or disseminated malignancy may prevent full recovery even if bile drainage is improved.^[ref] These are present capabilities, not a claim that modern endoscopy was available to the 1864 examiner.

The period question therefore calls for a conditional prognosis: a movable obstruction or reversible disturbance offers a better prospect than irreversible tissue destruction or an untreatable growing obstruction. A disappearing colour is not, by itself, proof that the underlying disease has been cured.

Enumerate the characteristics of what is termed ‘general Paralysis of the Insane?’ and state the diseases for which it may be mistaken.

General paresis combines progressive mental deterioration with a characteristic disorder of speech, fine movement and motor control. The historical phrase “general paralysis of the insane” does not mean complete, simultaneous immobility of every muscle.

Early changes may include impaired judgment, forgetfulness, altered personality, irritability, inappropriate confidence and loss of ordinary social restraint. Expansive or grandiose delusions are characteristic in some cases, but depression, suspiciousness or less spectacular cognitive failure can occur. Increasing dementia and reduced insight are more fundamental than any one extravagant belief.

The physical examination may disclose hesitating or slurred articulation, tremulous lips and tongue, facial tremor, deteriorating handwriting and impaired coordination of the hands. Gait becomes unsteady and weakness advances. Unequal or abnormally reacting pupils, altered reflexes and seizures may occur. Later disease can bring severe cognitive incapacity, swallowing difficulty, incontinence and dependence. Mental and motor manifestations need not develop in a fixed order or with equal severity.^[ref]

The name general paresis was already advocated in a January 1864 pathological study to avoid the ambiguity of “general paralysis.”^[ref] Modern medicine recognises the classical disease as a form of neurosyphilis, involving chronic injury to the brain. This causal diagnosis should be separated from the historical clinical label; it was not securely established by the wording of an 1864 examination. Syphilis serology, relevant cerebrospinal fluid findings and exclusion of alternative causes now help establish the diagnosis.^[ref]

Several mimics deserve explicit comparison. Mania can resemble the expansive mental phase, and depression or psychotic illness can resemble other presentations, but a sustained progressive combination of cognitive decline, characteristic speech disturbance and neurological signs argues for organic disease. Alcohol intoxication can produce tremor, slurred speech and an unsteady gait; an acute time course or improvement with clearance differs from progressive general paresis, although chronic alcohol-related disease may complicate the distinction. Other dementias, chronic cerebral vascular disease, tumours and some toxic or metabolic disorders can likewise combine cognitive and motor abnormalities.

A focal stroke generally gives a more abrupt and lateralised deficit; a series of strokes can produce a stepwise course. Parkinsonism can impair speech and gait but has a different predominant motor pattern. Tabes dorsalis can produce marked sensory ataxia, absent tendon reflexes and bladder disturbance with relatively preserved intellect; it can also coexist with paretic disease. The diagnosis rests on the pattern, course and corroborating investigation, not on grandiosity or a tremulous tongue alone.^[ref]

By what symptoms would you form a diagnosis of Hæmorrhage into the spinal cord ?

A sudden spinal syndrome—often pain followed rapidly by weakness, a sensory level and sphincter disturbance—would raise suspicion of haematomyelia. Symptoms can localise injury to the spinal cord, but cannot prove that the material within it is blood.

The classical presentation is abrupt severe spinal or radicular pain followed by rapid loss of motor power below the affected level. A thoracic lesion can produce paraplegia; a cervical lesion can affect all four limbs, and a high cervical lesion can impair breathing. Bladder retention or loss of control and bowel disturbance support interruption of descending spinal pathways. Sensory examination may show a sensory level below which sensation is altered; the distribution need not be perfectly symmetrical.

A centrally placed haemorrhage can especially injure crossing spinothalamic pathways and the anterior horns. There may therefore be disproportionate loss of pain and temperature with relative preservation of some other modalities, together with segmental weakness, reduced reflexes or later wasting at the level of the lesion. Damage to descending motor pathways produces weakness below it. Acute spinal shock can initially suppress reflexes below the lesion; later reflex behaviour depends on the pathways destroyed and should not be predicted from the first examination alone.^[ref]

The history should look for trauma, a bleeding disorder or anticoagulant exposure, a vascular malformation or an underlying spinal lesion. In a modern assessment these are possible causes, not prerequisites. A haemorrhage can also develop subacutely or recur, so the apoplectic onset is suggestive rather than universal.^[ref]

Important alternatives are spinal cord infarction, acute inflammatory myelitis, traumatic injury without intramedullary bleeding, and an epidural or other extramedullary collection compressing the spinal cord. A spinal meningeal bleed is anatomically different from haematomyelia, even if pain and weakness overlap. Preserved consciousness and absence of cranial signs may support spinal localisation, but neither is an absolute rule.

Modern magnetic resonance imaging is required to demonstrate the location and nature of the lesion; it can distinguish intramedullary blood from external compression and guide investigation of an underlying vascular or neoplastic cause.^[ref] In an 1864 answer, sudden onset and anatomical localisation justify a suspected diagnosis; they do not justify claiming certainty from symptoms alone.

Enumerate the varieties of Hernia that occur in the abdomen; and enumerate the swellings which may occur in the inguinal and scrotal regions, besides inguinoscrotal Hernia.

Abdominal hernias are classified primarily by the opening through which tissue protrudes; groin and scrotal swellings have a substantially wider differential diagnosis. Reducibility, obstruction and strangulation describe the state of a hernia, rather than different anatomical sites.

The principal external varieties are indirect inguinal hernia and direct inguinal hernia, femoral hernia, umbilical hernia and other anterior abdominal-wall hernias, including epigastric hernia and incisional hernia. An indirect inguinal hernia enters through the deep inguinal ring lateral to the inferior epigastric vessels and can follow the canal into the scrotum; a direct inguinal hernia passes through the posterior wall medial to those vessels. A femoral hernia passes through the femoral canal below the inguinal ligament, rather than along the inguinal canal.^[ref]

Less common wall or pelvic varieties include lateral ventral hernia, lumbar hernia, obturator hernia, sciatic hernia and perineal hernia. Diaphragmatic hernia defects allow abdominal contents into the thorax. Internal hernias can pass through a mesenteric or peritoneal aperture while remaining within the abdominal cavity, including paraduodenal recesses or the epiploic foramen. Contents may be intestine, omentum or other viscera; a developmental route and an acquired wall weakness can yield different forms at the same broad site.^[ref][ref]

In the groin, alternatives to an inguinoscrotal hernia include enlarged or inflamed lymph nodes, an abscess, lipoma of the spermatic cord or other soft tissue, a retained or undescended testis, a hydrocele of the cord, a saphena varix, and a femoral aneurysm or pseudoaneurysm. A femoral hernia is also an important separate diagnosis. A fluid collection along a persistent female inguinal peritoneal process can produce a corresponding inguinal swelling. These lesions are not interchangeable merely because they lie near the inguinal opening.^[ref]

In the scrotum, consider hydrocele, haematocele, spermatocele or an epididymal cyst, varicocele, epididymitis, orchitis, abscess, traumatic swelling and a testicular tumour. Torsion of the testis or its appendages can cause acute painful swelling. General oedema or lymphoedema can enlarge the scrotal wall diffusely rather than create one discrete lump.^[ref][ref]

The discriminating examination locates the swelling relative to the inguinal ligament and to the testis, asks whether it is cystic or solid, and notes posture-related change, reducibility, cough impulse and transillumination when relevant. A cough impulse is not exclusive to a hernia; a communicating fluid collection or a venous swelling may vary with pressure. Modern ultrasonography, including assessment of blood flow when indicated, can clarify uncertain anatomy. The site and character of a swelling must be established before it is called an inguinoscrotal hernia.

Describe the various modes of growth in Fibrous Tumours of the Uterus.

The principal modes are growth within the uterine wall, towards the cavity, and towards the outer surface: intramural uterine fibroids, submucosal uterine fibroids and subserosal uterine fibroids. “Fibrous tumour” is the historical label; the usual modern lesion is a leiomyoma, a benign growth of smooth muscle with a variable connective-tissue component, rather than a mass of collagen alone.^[ref]

An intramural uterine fibroid enlarges within the myometrium. It can remain enclosed by uterine muscle, push the cavity aside, or expand both inner and outer contours. Several nodules can give an irregularly enlarged uterus. Expansion compresses surrounding tissue into a cleavage plane or pseudocapsule; this differs from the destructive infiltrative growth typical of a malignant lesion.

A submucosal uterine fibroid grows towards the endometrium, projecting into and distorting the uterine cavity. It may remain broad-based or acquire a stalk as the surrounding wall is displaced. A pedunculated uterine fibroid can be pushed through the cervical canal and appear in the vagina as a uterine polyp. A polyp formed in this way is a mode of presentation of the same smooth-muscle tumour, not necessarily a different histological species. Its relation to the cavity helps explain why a comparatively small lesion may be associated with substantial bleeding.

A subserosal uterine fibroid projects outwards beneath the serosal covering. It may have a broad attachment or a long pedicle and become a large extrauterine-looking mass. Lateral outward growth can extend between the layers of the broad ligament; cervical growth can displace neighbouring pelvic structures. Rarely, a detached pedunculated lesion gains a blood supply from adjacent tissues and persists as a parasitic growth; this is not ordinary distant metastasis.^[ref]

The three directions are not mutually exclusive: a large nodule may affect both the uterine cavity and its external surface. Modern location classifications describe its relation to endometrium, myometrium and serosa more precisely, but those later type numbers are unnecessary to explain the anatomical modes requested here.

Growth is also distinct from secondary change. A poorly supplied area can undergo hyaline or cystic degeneration, haemorrhagic change or calcification; these changes alter consistency without establishing a new malignant mode of growth. Uterine fibroids often respond to the reproductive hormonal environment and commonly shrink after menopause, but neither every lesion's course nor its rate of growth is identical.^[ref] Location and attachment describe the mode of expansion; tissue examination establishes the nature of the tumour.